http://togogenome.org/gene/10090:Barx1 ^@ http://purl.uniprot.org/uniprot/Q9ER42 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BAR homeobox family.|||Expressed in areas of the first and second branchial arches, before any apparent cellular or morphologic differentiation. Later in development, all expressing tissue in this region, including the mesenchyme underlying the olfactory epithelium, the primary and secondary palate, the molar tooth papillae, and the stroma of the submandibular gland, appear to be derived from ectomesenchyme of neural crest origin. By day 16.5, all areas except the developing molars are BARX1-negative. In addition, BARX1 marks the area of the future stomach in the primitive gut at embryonic day 9.5, and is present in the mesenchymal wall of the stomach until embryonic day 16.5.|||Expressed predominantly in the facial primordia, developing stomach, and proximal limbs.|||Nucleus|||Transcription factor, which is involved in craniofacial development, in odontogenesis and in stomach organogenesis. May have a role in the differentiation of molars from incisors. Plays a role in suppressing endodermal Wnt activity. Binds to a regulatory module of the NCAM promoter. http://togogenome.org/gene/10090:Zfyve27 ^@ http://purl.uniprot.org/uniprot/Q3TXX3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Astrocytes express both isoform 1 and isoform 2 and oligodendrocytes express only isoform 2 (at protein level). Isoform 1 is expressed specifically in the central nervous system and selectively in neuronal cells. Isoform 2 is expressed in cerebrum, cerebellum, spinal cord, heart, thymus, spleen, intestine and lung.|||Can form homooligomers (monomers, dimers and tetramers) (By similarity). Interacts with RAB11A (GDP-bound form); regulates RAB11A (PubMed:21976701). Interacts with FKBP8; may negatively regulate ZFYVE27 phosphorylation (By similarity). Isoform 1 interacts to a greater extent than isoform 2 with VAPB (via MSP domain). Isoform 1 interacts to a greater extent than isoform 2 with VAPA (via MSP domain) (PubMed:24251978). Interaction with VAPA may regulate ZFYVE27 retention in the endoplasmic reticulum and its function in cell projections formation. Interacts with ATL2, ATL3, SPAST and RTN3 (By similarity). Interacts with REEP1, REEP5 and ATL1 (PubMed:24668814). Interacts with RAB11B (GDP-bound form), SURF4, KIF5B and KIF5C (PubMed:21976701). Isoform 1 and 2 interact with KIFA (PubMed:21976701, PubMed:24251978).|||Endoplasmic reticulum membrane|||Key regulator of RAB11-dependent vesicular trafficking during neurite extension through polarized membrane transport (By similarity). Promotes axonal elongation and contributes to the establishment of neuronal cell polarity (PubMed:24251978). Involved in nerve growth factor-induced neurite formation in VAPA-dependent manner. Contributes to both the formation and stabilization of the tubular ER network. Involved in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections (By similarity). Acts as an adapter protein that facilitates the interaction of KIF5A with VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 and the ZFYVE27-KIF5A complex contributes to the transport of these proteins in neurons. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a KIF5A/B-dependent manner (PubMed:21976701).|||Phosphorylated. Phosphorylation is induced by NGF through the MAPK/ERK pathway and modulates interaction with RAB11A (Probable).|||Recycling endosome membrane|||growth cone membrane http://togogenome.org/gene/10090:Ift46 ^@ http://purl.uniprot.org/uniprot/Q9DB07 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT46 family.|||By BMP2.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88. Interacts with IFT57, IFT88 and DAW1. Interacts with ARL13B. Interacts with IFT56. Interacts with TTC25 (PubMed:25860617). Interacts with IFT70B (PubMed:23810713).|||Expressed from 8 dpc throughout embryonic development, with levels increasing at 12.5 dpc and remaining constant thereafter. Up-regulated during chondrocyte maturation and skeletogenesis.|||Forms part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia. May play a role in chondrocyte maturation and skeletogenesis.|||Short cilia.|||Strongly expressed in ovary and testis, moderately expressed in kidney and brain, and weakly expressed in thymus, heart, lung, liver, spleen and muscle. Expressed in embryonic bone and cartilage, with high expression in non-hypertrophic chondrocytes and weaker expression in hypertrophic chondrocytes.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Dapk2 ^@ http://purl.uniprot.org/uniprot/Q8VDF3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase.|||Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha receptors.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.|||Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Capable of regulating both type I apoptotic and type II autophagic cell death signals. The former involves caspase activation, chromatin and mitochondrial condensation while the latter involves caspase-independent cell death in conjunction with accumulation of mature autophagic vesicles, plasma membrane blebs, and nuclear condensation without DNA degradation. Mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (By similarity). Regulates granulocytes motility by controlling cell spreading and polarization (PubMed:24163421).|||Cytoplasm|||Expressed in peritubular interstitial cells of the renal cortex (PubMed:24906443). Isoform 1 is found in the adult brain while isoform 2 is expressed in brains of embryos and young mice (at protein level) (PubMed:21408167).|||Homodimer in its autoinhibited state. Active as monomer. Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and suppresses DAPK2 kinase activity and DAPK2-induced apoptosis.|||No visible phenotype.|||The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.|||autophagosome lumen http://togogenome.org/gene/10090:Gfra1 ^@ http://purl.uniprot.org/uniprot/P97785 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 2 molecules of GDNFR-alpha are thought to form a complex with the disulfide-linked GDNF dimer and with 2 molecules of RET (By similarity). Interacts with RET (By similarity). Interacts with SORL1, either alone or in complex with GDNF. Interaction between SORL1 and GFRA1 leads to GFRA1 internalization, but not degradation (By similarity).|||Belongs to the GDNFR family.|||Cell membrane|||Endosome|||Expressed in the brain, in hippocampal neurons (at protein level) (PubMed:23333276). Isoform 1 and isoform 2 are expressed in heart, brain, lung, liver, kidney and testis.|||Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor (By similarity).|||multivesicular body|||trans-Golgi network http://togogenome.org/gene/10090:Ripk3 ^@ http://purl.uniprot.org/uniprot/Q9QZL0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts (via RIP homotypic interaction motif) with murid herpesvirus protein RIR1; this interaction disrupts RIP3-RIP1 interactions characteristic of TNF-alpha induced necroptosis, thereby suppressing this death pathway.|||Activity is stimulated by ZBP1, which senses double-stranded Z-RNA structures (PubMed:32200799, PubMed:32296175). RIPK3-dependent necroptosis is inhibited by RIPK1: RIPK1 prevents the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:27321907, PubMed:27819681, PubMed:27819682, PubMed:32296175). Inhibited by type II inhibitor 1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide (PubMed:32184955).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Expressed in embryo and in adult spleen, liver, testis, heart, brain and lung.|||Interacts (via RIP homotypic interaction motif) with RIPK1 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necrosis-inducing complex (PubMed:27321907, PubMed:27819681, PubMed:28842570, PubMed:31519887). Interacts with MLKL; the interaction is direct and triggers necroptosis (PubMed:24012422, PubMed:27321907). Interacts with ZBP1 (via RIP homotypic interaction motif); interaction with ZBP1 activates RIPK3, triggering necroptosis (PubMed:19590578, PubMed:22423968, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:28607035, PubMed:32200799). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity (By similarity). Binds TRAF2 and is recruited to the TNFR-1 signaling complex (By similarity). Interacts with PYGL, GLUL and GLUD1; these interactions result in activation of these metabolic enzymes (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (By similarity). Interacts with ARHGEF2 (By similarity). Interacts with PELI1 (via atypical FHA domain); the phosphorylated form at Thr-187 binds preferentially to PELI1 (PubMed:29883609). Interacts with BUB1B, TRAF2 and STUB1 (By similarity). Interacts with CASP6 (By similarity). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287).|||No visible phenotype in normal conditions; mice are viable and indistinguishable from wild-type mice (PubMed:14749364, PubMed:24557836). Mice are resistant to TNF-induced hypothermia (PubMed:24557836). Mice are more susceptible to influenza A virus (IAV) infection than wild-type mice: at a modestly lethal dose of IAV, mice display significantly increased rates of mortality, probably caused by a failure to eliminate infected cells and limit virus spread in pulmonary tissue (PubMed:27321907, PubMed:32200799). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Ripk3; mice however die the first days of postnatal life (PubMed:24813849, PubMed:24813850, PubMed:27819681, PubMed:27819682). Only mice lacking Ripk1, Ripk3 and Casp8 survive past weaning and rescue lethality caused by the absence of Ripk1 (PubMed:24813849, PubMed:24813850).|||Nucleus|||Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Ubiquitinated by STUB1 leading to its subsequent proteasome-dependent degradation.|||RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). Autophosphorylated following interaction with ZBP1 (PubMed:27819681). Phosphorylation of Ser-204 plays a role in the necroptotic function of RIPK3 (By similarity). Autophosphorylates at Thr-231 and Ser-232 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL (PubMed:23612963, PubMed:27819682). Phosphorylation at Thr-187 is important for its kinase activity, interaction with PELI1 and for its ability to mediate TNF-induced necroptosis (By similarity).|||Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death (PubMed:27321907, PubMed:27746097, PubMed:27917412, PubMed:28607035, PubMed:32200799, PubMed:32296175). Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1 (PubMed:19590578, PubMed:22423968, PubMed:24012422, PubMed:24019532, PubMed:24557836, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:24095729, PubMed:32200799, PubMed:27321907, PubMed:32296175). Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:24813849, PubMed:24813850, PubMed:27321907). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (PubMed:32200799, PubMed:32296175). Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity (PubMed:27321907). Phosphorylates RIPK1: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). In some cell types, also able to restrict viral replication by promoting cell death-independent responses (PubMed:30635240). In response to flavivirus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with ZBP1, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate (PubMed:30635240). Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed:30635240). RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL (By similarity). These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production (By similarity).|||The RIP homotypic interaction motif (RHIM) mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3).|||cytosol http://togogenome.org/gene/10090:Clec4a2 ^@ http://purl.uniprot.org/uniprot/Q9QZ15 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner. Involved in regulating immune reactivity. Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8(+) T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8(+) T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13. In plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF production (By similarity). May be involved via its ITIM motif (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation (PubMed:11841542).|||Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Expressed in splenic antigen-presenting cells including B-cells, monocytes/macrophages, and dendritic cells (at protein level). Expressed in spleen and lymph node and slightly increased with dendritic cell maturation.|||May be involved in regulating immune reactivity. May play a role in modulating dendritic cells (DC) differentiation and/or maturation (By similarity). May be involved in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation.|||May interact with PTPN6 via its ITIM site. http://togogenome.org/gene/10090:Fancm ^@ http://purl.uniprot.org/uniprot/Q8BGE5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DEAH subfamily. FANCM sub-subfamily.|||Component of the Fanconi anemia (FA) core complex, which consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FAAP24 and FAAP100. The FA core complex associates with Bloom syndrome (BLM) complex, which consists of at least BLM, DNA topoisomerase 3-alpha/TOP3A, RMI1/BLAP75, RPA1/RPA70 and RPA2/RPA32. This supercomplex between FA and BLM complexes has been called BRAFT. Forms a discrete complex with CENPS and CENPX, called FANCM-MHF; this interaction stimulates DNA binding and replication fork remodeling by FANCM and stabilizes the binding partners. Forms a heterodimer with FAAP24; this interaction increases FANCM single-stranded DNA-binding activity.|||DNA-dependent ATPase component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage. In complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA) and Holliday junction substrates. Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork. This activity is strongly stimulated in the presence of CENPS and CENPX. In complex with FAAP24, efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates. In vitro, on its own, strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA.|||Nucleus|||Phosphorylated; hyperphosphorylated in response to genotoxic stress. http://togogenome.org/gene/10090:Pbrm1 ^@ http://purl.uniprot.org/uniprot/F8VQD1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Kcna10 ^@ http://purl.uniprot.org/uniprot/B2RQA1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.8/KCNA10 sub-subfamily.|||Detected in the cochlear duct from 14.5 dpc (PubMed:22446089). Detected in the organ of Corti and the vestibular system from 16.5 dpc onwards, where it is most strongly expressed in hair cells (PubMed:22446089, PubMed:23528307).|||Expressed strongly in the inner ear and weakly in skeletal muscle. Not detected in other tissues.|||Homotetramer. Interacts with KCN4B/POMP. Interaction with KCN4B/POMP is necessary for the modulation of channel activity by cAMP.|||Mediates voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. The channel activity is up-regulated by cAMP.|||Membrane|||The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||Viable with no gross defects. Vestibular evoked potentials (VsEPs) are highly abnormal suggesting impaired function of the balance organ, although mice do not display any obvious imbalance behaviors. http://togogenome.org/gene/10090:Car13 ^@ http://purl.uniprot.org/uniprot/Q9D6N1 ^@ Activity Regulation|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the alpha-carbonic anhydrase family.|||Expressed in spleen, lung, kidney, heart, brain, skeletal muscle and testis.|||Inhibited by coumarins, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt).|||Reversible hydration of carbon dioxide. http://togogenome.org/gene/10090:Lrrtm1 ^@ http://purl.uniprot.org/uniprot/Q8K377 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LRRTM family.|||Cell membrane|||Exhibits strong synaptogenic activity, restricted to excitatory presynaptic differentiation, acting at both pre- and postsynaptic level.|||Expressed predominantly in the nervous system by postmitotic neurons, but also in some non-neuronal tissues. In adult brain expression is most prominent in the forebraain, particularly in the thalamus and in the cortical areas including hippocampus, piriform and posterior cingulate.|||Initially detected at 9 dpc with expression present in the overlying ectoderm of the limb bud in the presumptive apical ectodermal ridge. Expression is also seen in the dorsal otic vesicle in the presumptive endolymphatic appendage. Neural expression is present in the forebrain and midbrain with a sharp boundary across the central midbrain. Expression is also seen in the hindbrain. A stripe of expression can be detected in the neural tube. At 10 and 11 dpc expression is restricted to the apical ectodermal ridge. Expression persists in the endolymphatic diverticular appendage of the otic vesicle the forebrain/midbrain and the ventricular layer of the central neural tube through these stages.|||Mutant animals survive in the expected Mendelian ratios, are fertile and display no overt phenotype. Brain morphology appears grossly normal, except for rare cases of anomalous ventroculomegaly. Increase in the presynaptic area occupied by SLC17A7/VGLUT1 in some strata of the hippocampal neuropil of the CA1 region.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Cnot3 ^@ http://purl.uniprot.org/uniprot/Q8K0V4 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNOT2/3/5 family.|||Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in metabolic regulation; may be involved in recruitment of the CCR4-NOT complex to deadenylation target mRNAs involved in energy metabolism. Involved in mitotic progression and regulation of the spindle assembly checkpoint by regulating the stability of MAD1L1 mRNA. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may involve histone deacetylases. Involved in the maintenance of embryonic stem (ES) cell identity; prevents their differentiation towards extraembryonic trophectoderm lineages.|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. In the complex interacts directly with CNOT2. Interacts with TIP120B and NANOS2 (PubMed:20133598). Interacts with EBF1 (By similarity).|||Decreased levels in liver and white adipose tissues upon fasting,.|||Expressed in embryonic stem (ES) cells and in inner cell mass (ICM) of the blastocyst.|||Nucleus|||P-body http://togogenome.org/gene/10090:Mobp ^@ http://purl.uniprot.org/uniprot/Q9D2P8 ^@ Function|||Subcellular Location Annotation ^@ May play a role in compacting or stabilizing the myelin sheath possibly by binding the negatively charged acidic phospholipids of the cytoplasmic membrane.|||perinuclear region http://togogenome.org/gene/10090:Plec ^@ http://purl.uniprot.org/uniprot/E9Q3W4|||http://purl.uniprot.org/uniprot/Q6S385|||http://purl.uniprot.org/uniprot/Q6S387|||http://purl.uniprot.org/uniprot/Q6S388|||http://purl.uniprot.org/uniprot/Q6S390|||http://purl.uniprot.org/uniprot/Q6S392|||http://purl.uniprot.org/uniprot/Q6S393|||http://purl.uniprot.org/uniprot/Q9QXS1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plakin or cytolinker family.|||Detected in eye lens fiber cells (at protein level) (PubMed:21745462). Expressed at high levels in lung, brain, small intestine, muscle, heart and skin with lower levels found in kidney, liver, uterus, spleen and salivary gland (PubMed:10556294).|||Homodimer or homotetramer (By similarity). Interacts (via actin-binding domain) with SYNE3 (PubMed:16330710). Interacts (via calponin-homology (CH) 1 domain) with VIM (via rod region) (PubMed:15128297). Interacts (via N-terminus) with DST isoform 2 (via N-terminus) (PubMed:19932097). Interacts with FER (PubMed:12200133). Interacts with TOR1A (PubMed:18827015). Interacts with ANK3 (By similarity). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (PubMed:21745462).|||Interacts with KRT14, heterodimers consisting of KRT8 and KRT18, heterodimers consisting of KRT5 and KRT14, heterodimers consisting of KRT14 and KRT15, and heterodimers consisting of KRT1 and KRT10 (PubMed:24940650). Interacts with DES and VIM (PubMed:24940650).|||Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. May be involved not only in the cross-linking and stabilization of cytoskeletal intermediate filaments network, but also in the regulation of their dynamics.|||Phosphorylated by CDK1; regulates dissociation from intermediate filaments during mitosis. Isoform PLEC-1A is phosphorylated on Ser-21. Isoform PLEC-1A is phosphorylated on Tyr-26.|||The N-terminus interacts with actin, the C-terminus with vimentin, desmin, GFAP, cytokeratins, lamin B; whereas both the N- and the C-terminus can bind integrin beta-4.|||cytoskeleton|||hemidesmosome http://togogenome.org/gene/10090:Ppdpf ^@ http://purl.uniprot.org/uniprot/Q9CR37 ^@ Function|||Similarity ^@ Belongs to the PPDPF family.|||Probable regulator of exocrine pancreas development. http://togogenome.org/gene/10090:Slc25a12 ^@ http://purl.uniprot.org/uniprot/Q8BH59 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Homodimer (via N-terminus).|||Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle (By similarity). Also mediates the uptake of L-cysteinesulfinate by mitochondria in exchange of L-glutamate and proton. Can also exchange L-cysteinesulfinate with aspartate in their anionic form without any proton translocation (By similarity).|||Mitochondrion inner membrane|||The EF-hand 2 domain within the regulatory N-terminal domain binds one calcium in the mitochondrial intermembrane space. Calcium triggers the binding of the regulatory N-terminal domain to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain. In the absence of calcium, the linker loop domain may close the vestibule and prevent substrates from entering the carrier domain. http://togogenome.org/gene/10090:Shisal1 ^@ http://purl.uniprot.org/uniprot/Q0VBP7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the shisa family.|||Membrane http://togogenome.org/gene/10090:Cox8c ^@ http://purl.uniprot.org/uniprot/A6H666 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIII family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Actr10 ^@ http://purl.uniprot.org/uniprot/Q9QZB7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin family.|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.|||Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin.|||cytoskeleton http://togogenome.org/gene/10090:Utf1 ^@ http://purl.uniprot.org/uniprot/Q6J1H4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional coactivator of ATF2.|||Binds to the N-terminal region of ATF2. Associates with the TFIID complex through interaction with TBP.|||Expressed mainly in pluripotent cells with expression rapidly down-regulated upon cell differentiation.|||First detected in the embryo at the blastocyst stage. Little or no expression detected in adult tissues.|||Nucleus|||Phosphorylated.|||The leucine-zipper domain is required for coactivation activity. When this domain is deleted, the protein is able to stimulate transcription from a number of gene promoters. http://togogenome.org/gene/10090:Thpo ^@ http://purl.uniprot.org/uniprot/P40226|||http://purl.uniprot.org/uniprot/Q543R9 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the EPO/TPO family.|||Expression in the liver and bone marrow displays diurnal rhythmicity (a circadian rhythm that is synchronized with the day/night cycle).|||Found mainly in the liver, kidney and skeletal muscle.|||Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.|||Secreted|||Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal. http://togogenome.org/gene/10090:Cox6b1 ^@ http://purl.uniprot.org/uniprot/P56391 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 6B family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ivl ^@ http://purl.uniprot.org/uniprot/G3X9D9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the involucrin family.|||Cytoplasm|||Directly or indirectly cross-linked to cornifelin (CNFN).|||Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia.|||Substrate of transglutaminase. http://togogenome.org/gene/10090:Ercc2 ^@ http://purl.uniprot.org/uniprot/O08811 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. XPD/ERCC2 acts by forming a bridge between CAK and the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.|||Belongs to the helicase family. RAD3/XPD subfamily.|||Binds 1 [4Fe-4S] cluster.|||Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. The interaction with GTF2H2 results in the stimulation of the 5'-->3' helicase activity. Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with CIAO1 and CIAO2B; the interaction WITH CIAO2B is direct. Interacts with ATF7IP. Interacts directly with MMS19.|||ISGylated.|||Nucleus|||spindle http://togogenome.org/gene/10090:Cbx5 ^@ http://purl.uniprot.org/uniprot/Q61686 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Component of heterochromatin that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression. In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph). Can interact with lamin-B receptor (LBR). This interaction can contribute to the association of the heterochromatin with the inner nuclear membrane. Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins (By similarity).|||Interacts directly with ATRX, CHAF1A, LBR, NIPBL, SP100 and STAM2 via the chromoshadow domain. Can interact directly with CBX3 via the chromoshadow domain. Interacts with histone H3 methylated at 'Lys-9'. Interacts with BAHD1, SETDB1, MIS12 and DSN1. Interacts with POGZ; POGZ and PXVXL motif-containing proteins such as INCENP and TRIM28 compete for interaction with CBX5. Interacts with INCENP. Interacts with CHAMP1 (By similarity). Interacts directly with TRIM28 via the chromoshadow domain (PubMed:8978696). Interacts with KMT5B and KMT5C (PubMed:15145825). Interacts with HP1BP3 and TRIM24 (PubMed:8978696). Interacts with PRR14 (via N-terminus) (By similarity). Interacts with RRP1B (By similarity). Interacts with HNRNPU (via C-terminus); this interaction is, at least in part, RNA-dependent (By similarity). Interacts with LRIF1 (via PxVxL motif) (By similarity). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). May form homodimers (PubMed:8978696). Interacts with SMYD5 (PubMed:28250819). Interacts with CHD3 (By similarity). Interacts with CHD4 (By similarity).|||Nucleus|||Phosphorylation of HP1 and LBR may be responsible for some of the alterations in chromatin organization and nuclear structure which occur at various times during the cell cycle. Phosphorylated during interphase and possibly hyper-phosphorylated during mitosis.|||Ubiquitinated.|||centromere http://togogenome.org/gene/10090:Rhox2c ^@ http://purl.uniprot.org/uniprot/A2AWL9|||http://purl.uniprot.org/uniprot/V9GXB9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ibsp ^@ http://purl.uniprot.org/uniprot/Q61711 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation ^@ Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. Promotes Arg-Gly-Asp-dependent cell attachment (By similarity).|||It is possible that the segments of clustered carboxyl groups mediate the strong binding to hydroxyapatite.|||N-glycosylated; glycans consist of sialylated and core-fucosylated bi-, tri- and tetraantennary chains.|||Secreted|||Sulfated on either Tyr-320 or Tyr-321. http://togogenome.org/gene/10090:Sart3 ^@ http://purl.uniprot.org/uniprot/Q9JLI8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cajal body|||Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. Interacts with AGO1 and AGO2. Interacts with PRPF3 and USP4; the interaction with PRPF3 is direct and recruits USP4 to its substrate PRPF3. Interacts with USP15; the interaction is direct.|||Cytoplasm|||Expressed from early prenatal stages, as early as 7 dpc and increased thereafter.|||Knockout of Sart3 is embryonic lethal.|||Nucleus speckle|||U6 snRNP-binding protein that functions as a recycling factor of the splicing machinery. Promotes the initial reassembly of U4 and U6 snRNPs following their ejection from the spliceosome during its maturation. Also binds U6atac snRNPs and may function as a recycling factor for U4atac/U6atac spliceosomal snRNP, an initial step in the assembly of U12-type spliceosomal complex. The U12-type spliceosomal complex plays a role in the splicing of introns with non-canonical splice sites. May also function as a substrate-targeting factor for deubiquitinases like USP4 and USP15. Recruits USP4 to ubiquitinated PRPF3 within the U4/U5/U6 tri-snRNP complex, promoting PRPF3 deubiquitination and thereby regulating the spliceosome U4/U5/U6 tri-snRNP spliceosomal complex disassembly. May also recruit the deubiquitinase USP15 to histone H2B and mediate histone deubiquitination, thereby regulating gene expression and/or DNA repair (By similarity). May play a role in hematopoiesis probably through transcription regulation of specific genes including MYC (PubMed:21447833).|||Ubiquitously expressed, with low level of expression in liver, heart and skeletal (PubMed:10761712). Also detected in hematopoietic cells (at protein level) (PubMed:21447833).|||Up-regulated in proliferating hematopoietic cells.|||nucleoplasm http://togogenome.org/gene/10090:Adora3 ^@ http://purl.uniprot.org/uniprot/Q3U4C5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. http://togogenome.org/gene/10090:Snrnp27 ^@ http://purl.uniprot.org/uniprot/Q8K194 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNUT3 family.|||May play a role in mRNA splicing.|||Nucleus|||Part of a tri-snRNP complex. http://togogenome.org/gene/10090:Vmn1r20 ^@ http://purl.uniprot.org/uniprot/K7N778 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rab26 ^@ http://purl.uniprot.org/uniprot/Q504M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Detected in zymogenic cells in the stomach.|||Golgi apparatus membrane|||Interacts with ADRA2B (By similarity). Interacts with RIMS1.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Mediates transport of ADRA2A and ADRA2B from the Golgi to the cell membrane. Plays a role in the maturation of zymogenic granules and in pepsinogen secretion in the stomach (By similarity). Plays a role in the secretion of amylase from acinar granules in the parotid gland.|||secretory vesicle membrane http://togogenome.org/gene/10090:Asf1a ^@ http://purl.uniprot.org/uniprot/Q9CQE6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ASF1 family.|||Chromosome|||Embryonic lethality at mid-gestation (9.5 dpc).|||Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly. Promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks: acts by mediating histone replacement at DSBs, leading to recruitment of the MMS22L-TONSL complex and subsequent loading of RAD51. Also involved in the nuclear import of the histone H3-H4 dimer together with importin-4 (IPO4): specifically recognizes and binds newly synthesized histones with the monomethylation of H3 'Lys-9' and acetylation at 'Lys-14' (H3K9me1K14ac) marks, and diacetylation at 'Lys-5' and 'Lys-12' of H4 (H4K5K12ac) marks in the cytosol. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit.|||Interacts with histone H3 (including both histone H3.1 and H3.3) and histone H4. Interacts with the CHAF1A, CHAF1B and RBBP4 subunits of the CAF-1 complex. Interacts with CABIN1, HAT1, HIRA, NASP, TAF1 and UBN1. Interacts with CDAN1. Found in a cytosolic complex with IPO4 and histones H3 and H4. Interacts with CREBBP.|||Nucleus|||Phosphorylated by TLK1 and TLK2. Highly phosphorylated in S-phase and at lower levels in M-phase. TLK2-mediated phosphorylation at Ser-192 prevents proteasome-dependent degradation. Phosphorylation at Ser-192 by PRKDC in response to DNA damage promotes the histone chaperone activity and ability to replace histones at double-strand breaks (DSBs) at stalled or collapsed replication forks, leading to RAD51 recruitment. http://togogenome.org/gene/10090:Hps6 ^@ http://purl.uniprot.org/uniprot/Q8BLY7 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS5 and HPS3. Interacts with biogenesis of lysosome-related organelles complex-1 (BLOC1). Interacts with dynein intermediate chain (By similarity). Interacts with AP-3 complex (PubMed:19010779). Interacts with DCTN1 (PubMed:25189619).|||Defects in Hps6 are the cause of Hermansky-Pudlak-like syndrome, a syndrome characterized by hypopigmented eyes and coat, melanosomes greatly reduced in number and morphologically bizarre, kidney proximal tubules secreting lysosomal enzymes into urine at greatly reduced rates, platelet dense granules deficient in critical components, such as serotonin and adenine nucleotides, leading to functionally abnormal platelets and prolonged bleeding times, and mast cell granules undergoing unregulated 'kiss-and-run' fusion at the plasma membrane.|||Early endosome membrane|||Lysosome membrane|||May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules (By similarity). Acts as cargo adapter for the dynein-dynactin motor complex to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Facilitates retrograde lysosomal trafficking by linking the motor complex to lysosomes, and perinuclear positioning of lysosomes is crucial for the delivery of endocytic cargos to lysosomes, for lysosome maturation and functioning (PubMed:25189619).|||Microsome membrane|||Widely expressed, with lowest expression in skeletal muscle.|||cytosol http://togogenome.org/gene/10090:Elp2 ^@ http://purl.uniprot.org/uniprot/Q91WG4 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat ELP2 family.|||Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6. Interacts with STAT3 and JAKs (PubMed:10954736).|||Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator comple catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.|||Cytoplasm|||Folds into a two seven-bladed beta-propeller structure which is required for elongator complex assembly.|||Nucleus|||The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification. http://togogenome.org/gene/10090:Bcas2 ^@ http://purl.uniprot.org/uniprot/Q9D287 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPF27 family.|||Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly in the complex with PRPF19, CDC5L and PLRG1.|||Nucleus|||Required for pre-mRNA splicing as component of the activated spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR).|||nucleolus http://togogenome.org/gene/10090:Vmn2r101 ^@ http://purl.uniprot.org/uniprot/E9PZS9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nipal4 ^@ http://purl.uniprot.org/uniprot/Q8BZF2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Ba(2+), Sr(2+) and Fe(2+) but to a much less extent than Mg(2+) (PubMed:18667602). May be a receptor for ligands (trioxilins A3 and B3) from the hepoxilin pathway (By similarity).|||Belongs to the NIPA family.|||Cell membrane|||Up-regulated by low magnesium ion levels. http://togogenome.org/gene/10090:Or8b49 ^@ http://purl.uniprot.org/uniprot/E9Q716 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam193b ^@ http://purl.uniprot.org/uniprot/Q3U2K0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM193 family.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Zfp445 ^@ http://purl.uniprot.org/uniprot/Q8R2V3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ About one-third of zygotic mutants survived to adulthood. They do not exhibit any loss of methylation imprints at ICRs in the brain and liver at 12.5 dpc (PubMed:30602440). Double zygotic mutations of ZFP57 and ZNF445 are embryonically lethal and embryos show no gross morphological abnormalities but significant reduction in size and weight at 11.5 dpc, a phenotype more pronounced than in ZFP57 mutant mice with a more severe loss of impinting (PubMed:30602440).|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions (ICRs) (PubMed:30602440). Acts together with ZFP57, but ZFP57 plays the predominant role in imprinting maintenance. In contrast, ZNF445 seems to be the major factor in human early embryonic imprinting maintenance (PubMed:30602440). http://togogenome.org/gene/10090:Or5p59 ^@ http://purl.uniprot.org/uniprot/Q14AB1|||http://purl.uniprot.org/uniprot/Q8VG05 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Ppp1r36 ^@ http://purl.uniprot.org/uniprot/D3Z0R2 ^@ Function|||Subunit ^@ Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.|||Interacts with PPP1CA. http://togogenome.org/gene/10090:Galt ^@ http://purl.uniprot.org/uniprot/A2AMS3|||http://purl.uniprot.org/uniprot/Q03249|||http://purl.uniprot.org/uniprot/Q3TQJ2 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the galactose-1-phosphate uridylyltransferase type 1 family.|||Binds 1 Fe cation per subunit.|||Binds 2 zinc ions per subunit.|||Homodimer.|||Plays an important role in galactose metabolism. http://togogenome.org/gene/10090:Slc15a2 ^@ http://purl.uniprot.org/uniprot/Q80XC0|||http://purl.uniprot.org/uniprot/Q9JM03 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.|||Interacts (via extracellular domain region) with trypsin.|||Membrane http://togogenome.org/gene/10090:Mtpap ^@ http://purl.uniprot.org/uniprot/Q9D0D3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-B-like family.|||Cytoplasm|||Homodimer.|||Mitochondrion|||Polymerase that creates the 3' poly(A) tail of mitochondrial transcripts. Can use all four nucleotides, but has higher activity with ATP and UTP (in vitro). Plays a role in replication-dependent histone mRNA degradation. May be involved in the terminal uridylation of mature histone mRNAs before their degradation is initiated. Might be responsible for the creation of some UAA stop codons which are not encoded in mtDNA (By similarity). http://togogenome.org/gene/10090:Ppfibp1 ^@ http://purl.uniprot.org/uniprot/Q8C8U0 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the liprin family. Liprin-beta subfamily.|||Forms homodimers and heterodimers. Interacts with S100A4 in a calcium-dependent mode (By similarity).|||May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A (By similarity).|||The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type beta/beta. The C-terminal, non-coiled coil regions mediate heterodimerization type beta/alpha and interaction with S100A4 (By similarity). http://togogenome.org/gene/10090:Agr2 ^@ http://purl.uniprot.org/uniprot/O88312 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AGR family.|||Endoplasmic reticulum|||Expressed in embryo at 15 dpc onwards.|||Expressed in lung, skeletal muscle, testis, liver, stomach, colon, small intestine, the goblet cells of the intestine and the mucuous neck cells of the stomach.|||Mice are viable but display altered production of mucus with loss of production of MUC2 despite expression of its mRNA. They also display an increase in mast cells in the intestine, an increased expression of inflammation-specific genes, and frequent rectal prolapse. This is associated with a higher susceptibility to colitis.|||Monomer and homodimer. Interacts with LYPD3 and DAG1 (alphaDAG1). Interacts with MUC2; disulfide-linked.|||Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells. Proto-oncogene that may play a role in cell migration, cell differentiation and cell growth (By similarity). Promotes cell adhesion (By similarity).|||Secreted http://togogenome.org/gene/10090:Rspry1 ^@ http://purl.uniprot.org/uniprot/Q8BVR6 ^@ Developmental Stage|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in embryonic bone during primary endochondral ossification. Strong localization is observed in the perichondrium and periostium (at protein level). Also expressed in embryonic and postnatal brain and craniofacial tissues. Expressed in skeletal muscles (PubMed:26497270).|||Secreted|||Shows relatively low expression levels in proliferating myoblasts. Expression peaks at around day 1 of differentiation into myotubes and decreases again by day 10, when assayed in C2C12 cell line (at protein level).|||Up-regulated in response to denervation-induced skeletal muscle atrophy. Induced by MYOD1. http://togogenome.org/gene/10090:Plet1 ^@ http://purl.uniprot.org/uniprot/Q8VEN2 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||GPI-anchored.|||In early embryos before gastrulation, it is specifically expressed in the distal-most part of the extraembryonic ectoderm, adjacent to the epiblast. Expression is highly restricted to the developing pharyngeal endoderm and mesonephros until day 11.5 of embryogenesis.|||Modulates leading keratinocyte migration and cellular adhesion to matrix proteins during a wound-healing response and promotes wound repair. May play a role during trichilemmal differentiation of the hair follicle.|||N-glycosylated.|||Present in hair follicle cells and sebaceous gland of skin, ciliated epithelial cells of trachea and bronchial tube, striated portion of submandibular gland, distal convoluted tubule cells of kidney, ciliated epithelial cells of oviduct, medulla of adrenal gland and anterior lobe of pituitary gland. Expressed in keratinocytes of the hair follicle at the trichilemmal zone corresponding to the terminally differentiated outermost suprabasal outer root sheath (ORS), including that of the sebaceous gland duct (SGD) and the directly adjacent upper distal end of the companion layer (CL). Expression is similar in all hair follicle growth stages. Also detected during both the early and late anagen phases above the bulge of stem cells. Expressed at the leading edge of the epidermal wound. Not expressed in the interfollicular epidermis (IFE), inner root sheath (IRS) and hair fiber. Highly expressed in placenta. Detected in mammary and prostate epithelia and in the pancreas (at protein level).|||Up-regulated during calcium-induced terminal differentiation of outer root sheath (ORS) keratinocytes. http://togogenome.org/gene/10090:Terf2 ^@ http://purl.uniprot.org/uniprot/D3YZ08|||http://purl.uniprot.org/uniprot/O35144 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.|||Binds the telomeric double-stranded 5'-TTAGGG-3' repeat.|||Homodimer.|||Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1. Interacts with TERF2IP. Interacts with NBN. Interacts with SLX4/BTBD12. Interacts with DCLRE1B/Apollo; the interaction is direct (By similarity). Interacts with TERF2IP/RAP1; the interaction is direct.|||Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres (By similarity).|||Nucleus|||Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites (By similarity).|||The HTH domain is an independent structural unit and mediates binding to telomeric DNA.|||The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2.|||telomere http://togogenome.org/gene/10090:Arhgef37 ^@ http://purl.uniprot.org/uniprot/A1IGU4 ^@ Function ^@ May act as a guanine nucleotide exchange factor (GEF). http://togogenome.org/gene/10090:Gm20919 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Rpl36al ^@ http://purl.uniprot.org/uniprot/P83882|||http://purl.uniprot.org/uniprot/Q5M9P1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL42 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Fscn2 ^@ http://purl.uniprot.org/uniprot/Q32M02 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an actin bundling protein. May play a pivotal role in photoreceptor cell-specific events, such as disk morphogenesis. Important for maintaining functional hair-cell bundles in the inner ear. May stiffen the longer stereocilia of hair-cell bundles in the inner ear enabling better force transmission to tip links.|||Belongs to the fascin family.|||Defects in Fscn2 lead to hair-cell degeneration in the inner ear and are a key contributor to the early-onset, age-related hearing loss (prebycusis) phenotype when in combination with waltzer cadherin 23 mutant.|||Developmentally regulated, appearing in inner-hair cell stereocilia during final stages of elongation.|||Expressed in the inner ear. Abundant in the utricle.|||cytoskeleton|||stereocilium http://togogenome.org/gene/10090:Il1r2 ^@ http://purl.uniprot.org/uniprot/P27931 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble form (sIL1R2) can also be produced by proteolytic cleavage at the cell surface (shedding) involving a metalloproteinase.|||Associates with IL1RAP to form a non-signaling interleukin-1 receptor complex.|||Belongs to the interleukin-1 receptor family.|||Cell membrane|||Membrane|||Non-signaling receptor for IL1A, IL1B and IL1RN. Reduces IL1B activities. Serves as a decoy receptor by competitive binding to IL1B and preventing its binding to IL1R1. Also modulates cellular response through non-signaling association with IL1RAP after binding to IL1B. IL1R2 (membrane and secreted forms) preferentially binds IL1B and poorly IL1A and IL1RN. The secreted IL1R2 recruits secreted IL1RAP with high affinity; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors (By similarity).|||Secreted|||Strongly expressed in B-cells, with levels 21 times higher than IL1R1. In T-cells expressed 5 times more compared with IL1R1. http://togogenome.org/gene/10090:Gtpbp10 ^@ http://purl.uniprot.org/uniprot/Q8K013 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.|||May be involved in the ribosome maturation process.|||nucleolus http://togogenome.org/gene/10090:Mtg2 ^@ http://purl.uniprot.org/uniprot/A2AFK4 ^@ Similarity ^@ Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. http://togogenome.org/gene/10090:H2az2 ^@ http://purl.uniprot.org/uniprot/B2RVP5|||http://purl.uniprot.org/uniprot/Q3THW5|||http://purl.uniprot.org/uniprot/Q8R029 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated on Lys-5, Lys-8 and Lys-12 during interphase. Acetylation disappears at mitosis.|||Belongs to the histone H2A family.|||Chromosome|||Monoubiquitination of Lys-122 gives a specific tag for epigenetic transcriptional repression.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. H2A or its variant H2AZ2 forms a heterodimer with H2B (By similarity).|||Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division (By similarity). http://togogenome.org/gene/10090:Cenpv ^@ http://purl.uniprot.org/uniprot/Q9CXS4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Gfa family.|||Binds 2 Zn(2+) ions per subunit.|||Nucleus|||Required for distribution of pericentromeric heterochromatin in interphase nuclei and for centromere formation and organization, chromosome alignment and cytokinesis.|||kinetochore|||spindle http://togogenome.org/gene/10090:Cenph ^@ http://purl.uniprot.org/uniprot/Q9QYM8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed between embryonic day 9.5 and 12.5.|||Abundantly expressed in thymus, spleen, uterus, ovary, testis and muscle, and weakly expressed in small intestine, lung and stomach. Barely detectable expression in kidney, liver, skin and prostate gland. Not detected in brain, heart or adrenal gland. Also expressed weakly in various hematopoietic cell lines.|||Belongs to the CENP-H/MCM16 family.|||Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate (By similarity).|||Nucleus|||Self-associates. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS (By similarity). Interacts directly with CENPK (By similarity). Interacts with KIF2C and NDC80 (By similarity). Interacts with TRIM36.|||kinetochore http://togogenome.org/gene/10090:Prpf38b ^@ http://purl.uniprot.org/uniprot/Q80SY5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PRP38 family.|||May be required for pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Shisal2b ^@ http://purl.uniprot.org/uniprot/Q9D1Y9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the shisa family.|||Membrane http://togogenome.org/gene/10090:Kdm4b ^@ http://purl.uniprot.org/uniprot/Q91VY5 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the JHDM3 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Expression is especially strong in the hippocampus and throughout the CNS from embryonic periods through adulthood.|||Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate (By similarity). Plays a critical role in the development of the central nervous system (CNS).|||Nucleus|||The 2 Tudor domains recognize and bind methylated histones. Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails (By similarity). http://togogenome.org/gene/10090:Dad1 ^@ http://purl.uniprot.org/uniprot/P61804 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DAD/OST2 family.|||Component of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes.|||Endoplasmic reticulum membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (By similarity). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. http://togogenome.org/gene/10090:Spty2d1 ^@ http://purl.uniprot.org/uniprot/Q68FG3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPT2 family.|||Histone chaperone that stabilizes pre-existing histone tetramers and regulates replication-independent histone exchange on chromatin. Required for normal chromatin refolding in the coding region of transcribed genes, and for the suppression of spurious transcription. Binds DNA and histones and promotes nucleosome assembly (in vitro). Facilitates formation of tetrameric histone complexes containing histone H3 and H4 (By similarity). Modulates RNA polymerase 1-mediated transcription (By similarity). Binds DNA, with a preference for branched DNA species, such as Y-form DNA and Holliday junction DNA (By similarity).|||Interacts with histones. Interacts with a heterotetrameric complex formed by histone H3 and H4, especially when the histone tetramer is not bound to DNA. Interacts with histone H3.3 (By similarity).|||The acidic C-terminal domain mediates interaction with histone H3/H4 complexes.|||nucleolus http://togogenome.org/gene/10090:G6pc2 ^@ http://purl.uniprot.org/uniprot/Q9Z186 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glucose-6-phosphatase family.|||Endoplasmic reticulum membrane|||G6pc2 is an autoantigen which is the natural target of a prevalent T-cell population causing insulin-dependent diabetes mellitus through destruction of pancreatic beta cells.|||Initial onset of expression in the pancreas is at 12 dpc and prominent expression is detected at 14 dpc.|||May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis (By similarity).|||Mice are no overt anatomical or behavioral phenotype but display a mild metabolic phenotype. Upon fasting those mice exhibit a significant decrease in blood glucose and triacylglycerol compared to wild-type mice.|||N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome.|||Specifically expressed in pancreatic islet cells, in particular those of beta-cell origin. Not detected in testis, kidney, muscle, liver, lung, spleen, brain, pituitary, gastric fundus or heart.|||Up-regulated in islet cells cultured in hyperglycemic concentrations of glucose. http://togogenome.org/gene/10090:Plscr3 ^@ http://purl.uniprot.org/uniprot/Q5F283|||http://purl.uniprot.org/uniprot/Q9JIZ9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phospholipid scramblase family.|||Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of the phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer membrane of the mitochondria (By similarity). Plays an important role in mitochondrial respiratory function, morphology, and apoptotic response (By similarity). Mediates the translocation of cardiolipin from the mitochondrial inner membrane to outer membrane enhancing t-Bid induced cytochrome c release and apoptosis (Probable). Enhances TNFSF10-induced apoptosis by regulating the distribution of cardiolipin in the mitochondrial membrane resulting in increased release of apoptogenic factors and consequent amplification of the activity of caspases (By similarity). Regulates cardiolipin de novo biosynthesis and its resynthesis (By similarity).|||May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane.|||Mitochondrion inner membrane|||Mitochondrion membrane|||Monomer (By similarity). Forms homooligomers upon binding to Ca(2+), Pb(2+) and Hg(2+) ions (By similarity). Interacts with PDCD6 in a calcium-dependent manner (By similarity). Interacts with PRKCD; interaction is enhanced by UV irradiation (PubMed:19428821).|||Nucleus|||Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus.|||The Proline-rich domain is required for phospholipid scramblase activity. http://togogenome.org/gene/10090:Zfp568 ^@ http://purl.uniprot.org/uniprot/E9PYI1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed ubiquitously at 7.5 dpc and 8.5 dpc, with especially high levels in the extraembryonic ectoderm (PubMed:18701545). Expressed strongly in head from stages 10.5 dpc to 12.5 dpc (PubMed:23071813). In fetal brain, shows highest expression levels at stage 13.5 dpc with low levels thereafter (PubMed:23071813). Detected in neural stem cells of the neocortex at stage 12.5 dpc (PubMed:23071813).|||Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but has also repression activity independently of this interaction (PubMed:22110054, PubMed:27658112). Essential during embryonic development, where it acts as direct repressor of IGF2-P0, placental-specific transcript of IGF2, in early development and regulates convergent extension movements required for axis elongation and tissue morphogenesis in all germ layers (PubMed:18701545, PubMed:22110054, PubMed:28522536). Also important for normal morphogenesis of extraembryonic tissues including the yolk sac, extraembryonic mesoderm and placenta (PubMed:18701545, PubMed:21094155). May enhance proliferation or maintenance of neural stem cells (PubMed:23071813).|||Interacts with TRIM28.|||KRAB domain 1, but not KRAB domain 2, is required for transcriptional repression. Both contribute to interaction with TRIM28. Differences in repressive activity between KRAB domain 1 and 2 are likely due to amino acid differences at multiple residues.|||Little or no expression detected in most adult tissues (brain, liver, kidney, spleen, testis, ovary). In the hippocampus, detected in neural stem cells within the subventricular zone and subgranular zone.|||May be due to competing acceptor splice site.|||Mutant embryos arrest at 9 dpc, they fail to complete gastrulation, have convergent-extension failure and a yolk sac membrane-ruffling phenotype (PubMed:28522536). Conditional knockdown in neural stem cells results in reduced brain weight at birth, however adult brain weights are normal and no other defects in brain development or morphology are apparent (PubMed:23071813). Double knockout for ZNF568 and IGF2 embryos and fetuses are found at near Mendelian ratios and indistiguishable of wild type littermates at 12.5 dpc to 18.5 dpc. However, after birth few dead pups are recovered (PubMed:28522536).|||Nucleus http://togogenome.org/gene/10090:Pcdhac1 ^@ http://purl.uniprot.org/uniprot/Q91Y10 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Mpc1 ^@ http://purl.uniprot.org/uniprot/D3Z5S0|||http://purl.uniprot.org/uniprot/P63030|||http://purl.uniprot.org/uniprot/Q3UX28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.|||Homodimer. Forms heterodimer with MPC2. The heterodimer is the more stable and dominant form.|||Mediates the uptake of pyruvate into mitochondria.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Kash5 ^@ http://purl.uniprot.org/uniprot/Q80VJ8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Required for telomere attachment to nuclear envelope in the prophase of meiosis and for rapid telomere prophase movements implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly. Required for homolog pairing during meiotic prophase in spermatocytes and probably oocytes. Essential for male and female gametogenesis. Recruits cytoplasmic dynein to telomere attachment sites at the nuclear envelope in spermatocytes. In oocytes is involved in meiotic resumption and spindle formation.|||Core component the LINC complex which is composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents is giving rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. Interacts (via the last 22 AA) with SUN1; this interaction mediates its telomere localization by forming a SUN1:KASH5 LINC complex. Component of a probable SUN2:KASH5 LINC complex. Self-associates. Interacts with DYNC1H1, DCTN1, DYNC1I1/2 and PAFAH1B1; suggesting the association with the dynein-dynactin motor complex.|||Nucleus|||Nucleus outer membrane|||Restricted to the testis and the early ootidogenesis ovary. Expressed in spermatocytes and oocytes (at protein level).|||The C-terminal 22 AA is required and sufficient for localization to telomeres at the nuclear envelope.|||telomere http://togogenome.org/gene/10090:Kcnh6 ^@ http://purl.uniprot.org/uniprot/M0QW64|||http://purl.uniprot.org/uniprot/Q32ME0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Angptl6 ^@ http://purl.uniprot.org/uniprot/Q8R0Z6 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Highly expressed in the liver, specifically in hepatocytes, and weakly in the heart. Expressed in hematopoietic cells, platelets and mast cells, and detected at wounded skin.|||May play a role in the wound healing process. May promote epidermal proliferation, remodeling and regeneration. May promote the chemotactic activity of endothelial cells and induce neovascularization. May counteract high-fat diet-induced obesity and related insulin resistance through increased energy expenditure.|||Secreted http://togogenome.org/gene/10090:Kif21b ^@ http://purl.uniprot.org/uniprot/F8VQE2|||http://purl.uniprot.org/uniprot/Q9QXL1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Cytoplasmic vesicle|||Expressed in brain (at protein level) (PubMed:27117409, PubMed:25172774). Expressed in spleen and at lower levels in testes (PubMed:10225949).|||Interacts with TRIM3; the interaction positively affects motility of KIF21B (PubMed:24086586). Interacts with GABARAP and GABA(A) receptor subunits: GABRG2, GABRA1 and GABRA2 (By similarity). May interact with GABA(A) receptor subunits: GABRB2 and GABRB3 (By similarity).|||Mutant mice exhibit behavioral changes involving learning and memory deficits.|||Plus-end directed microtubule-dependent motor protein which displays processive activity (PubMed:27117409, PubMed:10225949). Is involved in regulation of microtubule dynamics, synapse function and neuronal morphology, including dendritic tree branching and spine formation (PubMed:27117409). Plays a role in lerning and memory (PubMed:27117409). Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptor to cell surface (PubMed:25172774).|||axon|||cytoskeleton|||dendrite|||growth cone http://togogenome.org/gene/10090:Myrf ^@ http://purl.uniprot.org/uniprot/Q3UR85 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 3 (P3), the expression is restricted to cells in the hindbrain and cerebellum, subsequently spreading rostrally throughout the white matter tracks over the first 2 weeks postnatal, mirroring the expression of Plp1.|||Belongs to the MRF family.|||Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes.|||Cytoplasm|||Embryos die around 12.5 dpc. Conditional knockout mice in which Mrf is lacking within the oligodendrocyte lineage display severe deficits in myelin gene expression and premyelinating oligodendrocytes fail to myelinate. These mice display severe neurological abnormalities and die because of seizures during the third postnatal week.|||Endoplasmic reticulum membrane|||Expression is directly regulated by SOX10.|||Follows autocatalytic cleavage via the peptidase S74 domain. Autoprocessing is apparently constitutive and is essential for transcriptional activity (PubMed:23966833, PubMed:28623291, PubMed:30249802). Autocatalytic cleavage is inhibited by interaction with TMEM98 (PubMed:30249802).|||Glycosylated.|||Homotrimer (PubMed:23966833, PubMed:28623291). Interacts (via C-terminal region) with TMEM98; the interaction inhibits MYRF self-cleavage (PubMed:30249802).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Dubious isoform due to intron retention.|||Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage.|||Nucleus|||Specifically expressed by postmitotic oligodendrocytes in the CNS. Not detected in the peripheral nervous system (PNS).|||The nuclear localization signals mediate translocation to the nucleus.|||The peptidase S74 domain, also named Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecular Chaperone Domain (ICD), has protease activity and mediates autocatalytic processing of the protein to generate the Myelin regulatory factor, N-terminal active transcription factor and the Myelin regulatory factor, C-terminal components.|||Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination (PubMed:19596243, PubMed:22956843, PubMed:23966833, PubMed:24204311, PubMed:27532821). Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:19596243, PubMed:22956843, PubMed:23966833). http://togogenome.org/gene/10090:Nat1 ^@ http://purl.uniprot.org/uniprot/P50294|||http://purl.uniprot.org/uniprot/Q546L3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the arylamine N-acetyltransferase family.|||Cytoplasm|||Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Isoniazid, 2-aminofluorene and anisidine are preferred substrates for NAT-1. No activity with p-aminobenzoic acid (PABA) nor SMZ. http://togogenome.org/gene/10090:Syt11 ^@ http://purl.uniprot.org/uniprot/Q9R0N3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant across the brain, expression increases progressively over the first 2 weeks after birth.|||Belongs to the synaptotagmin family.|||Cytoplasmic vesicle membrane|||Expressed in cerebellun, cerebellar cortex, hippocampus, olfactory bulb and spinal cord (at protein level) (PubMed:30808661). Expressed by neurons, astrocytes and microglia (at protein level) (PubMed:28686317, PubMed:26450452). Expressed in macrophages (at protein level) (PubMed:23303671).|||Homodimer. Can also form heterodimers. Interacts with PRKN (By similarity). Interacts (via C2 2 domain) with AGO2 and SND1; the interaction with SND1 is direct (PubMed:24882364). Interacts with KIF1A; the interaction increases in presence of calcium (PubMed:30808661).|||Knockout is lethal (PubMed:30808661). Conditional knockout mice for dopaminergic neurons show increased dopamine release, accelerated vesicle pools replenishment and enlarged releasable vesicle pools in the striatum (PubMed:29311685). Forebrain-specific conditional knockouts are viable, fertile and have normal life span. They show impaired learning an memory (PubMed:30808661).|||Lysosome membrane|||Perikaryon|||Postsynaptic density|||Recycling endosome membrane|||Synaptotagmin family member involved in vesicular and membrane trafficking which does not bind Ca(2+) (Probable). Inhibits clathrin-mediated and bulk endocytosis, functions to ensure precision in vesicle retrieval (PubMed:29311685). Plays an important role in dopamine transmission by regulating endocytosis and the vesicle-recycling process (PubMed:29311685). Essential component of a neuronal vesicular trafficking pathway that differs from the synaptic vesicle trafficking pathway but is crucial for development and synaptic plasticity (PubMed:30808661). In macrophages and microglia, inhibits the conventional cytokine secretion, of at least IL6 and TNF, and phagocytosis (PubMed:28686317, PubMed:23303671). In astrocytes, regulates lysosome exocytosis, mechanism required for the repair of injured astrocyte cell membrane (PubMed:26450452). Required for the ATP13A2-mediated regulation of the autophagy-lysosome pathway (PubMed:27278822).|||The second C2 domain/C2B is required for the inhibitory role in both clathrin-mediated and bulk endocytosis. The transmembrane domain and the first C2 domain/C2A are critical for the inhibitory role in clathrin-mediated endocytosis or bulk endocytosis, respectively.|||Ubiquitinated, at least by PRKN, and targeted to the proteasome complex for degradation. Ubiquitination is inhibited by ATP13A2.|||Unlike in other synaptotagmin family members, the first C2 domain/C2A does not bind Ca(2+) neither mediates Ca(2+)-dependent phospholipid binding. An aspartate-to-serine substitution in this domain inactivates Ca(2+)/phospho-lipid binding.|||axon|||clathrin-coated vesicle membrane|||dendrite|||phagosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Lce1k ^@ http://purl.uniprot.org/uniprot/J3QP15 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:H2ac12 ^@ http://purl.uniprot.org/uniprot/A3KPD0|||http://purl.uniprot.org/uniprot/Q8CGP6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Nrxn2 ^@ http://purl.uniprot.org/uniprot/A0A494B8Y4|||http://purl.uniprot.org/uniprot/E9PUM9|||http://purl.uniprot.org/uniprot/E9Q5N7 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Gm20888 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Cfap69 ^@ http://purl.uniprot.org/uniprot/Q8BH53 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cilium- and flagellum-associated protein (PubMed:28495971, PubMed:29606301). In the olfactory epithelium, regulates the speed of activation and termination of the odor response and thus contributes to the robustness of olfactory transduction pathways (PubMed:28495971). Required for sperm flagellum assembly and stability (PubMed:29606301).|||Detected in pachytene spermatocytes and has increased expression in early and late spermatids.|||Expressed in ciliated olfactory sensory neurons (at protein level) (PubMed:28495971). Expressed in testis, specifically in sperm (at protein level) (PubMed:29606301).|||Male mice are infertile due to disrupted sperm flagellum assembly.|||cilium|||flagellum http://togogenome.org/gene/10090:Hypk ^@ http://purl.uniprot.org/uniprot/Q9CR41 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of several N-terminal acetyltransferase complexes (By similarity). Inhibits the N-terminal acetylation activity of the N-terminal acetyltransferase NAA10-NAA15 complex (also called the NatA complex) (By similarity). Has chaperone-like activity preventing polyglutamine (polyQ) aggregation of HTT in neuronal cells probably while associated with the NatA complex (By similarity). May play a role in the NatA complex-mediated N-terminal acetylation of PCNP (By similarity).|||Component of the N-terminal acetyltransferase A (NatA)/HYPK complex at least composed of NAA10, NAA15 and HYPK, which has N-terminal acetyltransferase activity (By similarity). Within the complex interacts with NAA10 (By similarity). Within the complex interacts with NAA15 (By similarity). Predominantly interacts with NAA15 in the NAA10-NAA15 complex (also called the NatA complex); the interaction with the NatA complex reduces the acetylation activity of the NatA complex (By similarity). Interacts with HTT (via N-terminus) (By similarity). The NatA complex is required for HYPK stability and for reducing polyQ aggregation of HTT (By similarity). Component of the N-terminal acetyltransferase E (NatE)/HYPK complex at least composed of NAA10, NAA15, NAA50 and HYPK (By similarity). Within the complex interacts with NAA10 and NAA15 (By similarity). Does not interact with NAA50 (By similarity). Interaction with NAA15 reduces the capacity of NAA15 to interact with NAA50 (By similarity). Its capacity to interact with the NatA complex is reduced by NAA50 (By similarity). Does not interact with the N-terminal acetyltransferase B (NatB) complex component NAA25 or the N-terminal acetyltransferase C (NatC) complex component NAA35 (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Slc18a2 ^@ http://purl.uniprot.org/uniprot/Q8BRU6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Vesicular transporter family.|||Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports a variety of catecholamines such as dopamine, adrenaline and noradrenaline, histamine, and indolamines such as serotonin (PubMed:10618388) (By similarity). Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates somatodendritic dopamine release in hippocampal neurons, likely as part of a regulated secretory pathway that integrates retrograde synaptic signals (By similarity). Acts as a primary transporter for striatal dopamine loading ensuring impulse-dependent release of dopamine at the synaptic cleft (PubMed:9427251). Responsible for histamine and serotonin storage and subsequent corelease from mast cell granules (PubMed:10618388) (By similarity).|||Expressed in striata and substantia nigra.|||Interacts with SLC6A3.|||Mice are born at the expected Mendelian rate. The homozygous mutants show severe growth retardation and the majority die shortly after birth.|||axon|||dendrite|||secretory vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Zc3h18 ^@ http://purl.uniprot.org/uniprot/Q0P678 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts with ZFC3H1 in a RNase-insensitive manner.|||Nucleus http://togogenome.org/gene/10090:Or5a1 ^@ http://purl.uniprot.org/uniprot/Q8VFV2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ryr2 ^@ http://purl.uniprot.org/uniprot/E9Q401|||http://purl.uniprot.org/uniprot/Q80ZZ5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 subfamily.|||Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2807 and Ser-2813 increases the open probability of the calcium channel. Phosphorylation is increased in failing heart, leading to calcium leaks and increased cytoplasmic Ca(2+) levels.|||Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) cytosolic levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.|||Embryonically lethal. Embryos die at about 10 dpc, due to defects in heart tube development. Cardiac myotubes display enlarged rough endoplasmic reticulum and cytoplasmic vesicles that contain high levels of Ca(2+).|||Highly expressed in heart, lung, cerebellum and brain. Detected at lower levels in adrenal gland, stomach, thymus, esophagus and ovary.|||Homotetramer. Can also form heterotetramers with RYR1 and RYR3. Interacts with CALM and S100A1; these interactions regulate channel activity. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A (By similarity). Interacts with FKBP1A and FKBP1B; these interactions may stabilize the channel in its closed state and prevent Ca(2+) leaks. Interacts with SELENON (By similarity). Identified in a complex, composed of FSD2, CMYA5 and RYR2 (PubMed:28740084).|||Phosphorylation at Ser-2030 by PKA enhances the response to lumenal calcium.|||Sarcoplasmic reticulum membrane|||The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm.|||The calcium release is activated by increased cytosolic calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites. http://togogenome.org/gene/10090:Pdcd6 ^@ http://purl.uniprot.org/uniprot/P12815 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ COPII-coated vesicle membrane|||Calcium sensor that plays a key role in processes such as endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal biogenesis or membrane repair (PubMed:10744743, PubMed:11525164, PubMed:27541325). Acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium: calcium-binding triggers exposure of apolar surface, promoting interaction with different sets of proteins thanks to 3 different hydrophobic pockets, leading to translocation to membranes (PubMed:10744743, PubMed:11525164, PubMed:27541325). Involved in ER-Golgi transport by promoting the association between PDCD6IP and TSG101, thereby bridging together the ESCRT-III and ESCRT-I complexes (PubMed:10744743, PubMed:11525164, PubMed:27541325). Together with PEF1, acts as calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in ER-Golgi transport by regulating the size of COPII coats (By similarity). In response to cytosolic calcium increase, the heterodimer formed with PEF1 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification (By similarity). Involved in the regulation of the distribution and function of MCOLN1 in the endosomal pathway (By similarity). Promotes localization and polymerization of TFG at endoplasmic reticulum exit site (By similarity). Required for T-cell receptor-, Fas-, and glucocorticoid-induced apoptosis (PubMed:8560270). May mediate Ca(2+)-regulated signals along the death pathway: interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (By similarity). Its role in apoptosis may however be indirect, as suggested by knockout experiments (PubMed:12024023). May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphorylation of the Akt signaling pathway (By similarity).|||Cytoplasm|||EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium-binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity (PubMed:11525164). A one-residue insertion in the EF5-binding loop prevents the glutamyl residue at the C-terminal end of the loop from serving as the canonical bidentate calcium ligand (PubMed:11525164). EF5 acts as a high-affinity magnesium-binding domain instead (PubMed:27541325). Magnesium, may affect dimerization (PubMed:27541325). EF5 may bind either calcium or magnesium depending on the context.|||Endoplasmic reticulum membrane|||Endosome|||Has a lower Ca(2+) affinity than isoform 1 (PubMed:10744743).|||Homodimer and heterodimer; heterodimerizes (via the EF-hand 5) with PEF1 (PubMed:10200558, PubMed:11525164, PubMed:27541325). Isoform 1 and isoform 2 self-associate; probably forming homodimers (By similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with PDCD6IP; the interaction is calcium-dependent (PubMed:10200558, PubMed:10744743, PubMed:11525164). Interacts with RBM22 (By similarity). Interacts with PLSCR4 (By similarity). Interacts with ANXA7 and TSG101 (By similarity). Interacts with DAPK1 (By similarity). Interacts with SEC31A; the interaction is calcium-dependent and promotes monoubiquitination of SEC31A (By similarity). Interacts with ANXA11 (via N-terminus); the interaction is calcium-dependent (By similarity). Interacts with PLSCR3 (via N-terminus); the interaction is calcium-dependent (By similarity). Interacts with MCOLN1; the interaction is calcium-dependent (By similarity). Interacts with KDR; the interaction is calcium-dependent (By similarity). Interacts with HEBP2; the interaction is calcium-dependent (By similarity). Interacts with TFG (By similarity). Isoform 1: Interacts with SHISA5, leading to stabilize it (PubMed:17889823). Isoform 2: Does not interact with SHISA5 (PubMed:17889823). Isoform 2: Does not interact with PDCD6IP, TSG101, ANXA7 and ANXA11 (PubMed:10744743).|||Interacts with different set of proteins thanks to 3 different hydrophobic pockets. Hydrophobic pockets 1 and 2, which mediate interaction with PDCD6IP, are largely formed by residues from EF-hand 3 (EF3) to 5 (EF5), as well as by Tyr-180 (EF5) of a dimerizing molecule (Pocket 1) and from EF-hand (EF2) to 4 (EF4) (Pocket 2). Hydrophobic pocket 3, which mediates interaction with SEC31A, is mainly formed by residues from EF-hand 1 (EF1) to 3 (EF3).|||No visible phenotype (PubMed:12024023). Mice develop normally and display no obvious immune defect (PubMed:12024023). T-cells retain susceptibility to apoptotic stimuli (PubMed:12024023).|||Nucleus http://togogenome.org/gene/10090:Slpi ^@ http://purl.uniprot.org/uniprot/P97430 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:9126337). Modulates the innate immune response after bacterial infection (PubMed:12615907). Contributes to regulate the inflammatory and immune responses to the intracellular parasite L.major (PubMed:25030421). Down-regulates responses to bacterial lipopolysaccharide (LPS) (PubMed:9039268, PubMed:12615907, PubMed:25030421). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses (PubMed:11017147, PubMed:12615907). Has antimicrobial activity against mycobacteria, but not against salmonella (PubMed:18322212). Contributes to normal resistance against infection by M.tuberculosis (PubMed:18322212). Required for normal resistance to L.major (PubMed:25030421). Required for normal wound healing, probably by preventing tissue damage by limiting protease activity (PubMed:11017147, PubMed:25030421). Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells (By similarity).|||Detected in bronchial epithelial cells (PubMed:18322212). Detected in bronchoalveolar fluid after infection with M.tuberculosis (at protein level) (PubMed:18322212). Highest expression in lung, spleen, intestine and epididymis with lower levels in liver and seminal vesicle. No expression in brain, heart, kidney and muscle.|||Interacts with GRN; interaction protects progranulin from proteolysis.|||Mutant mice show delayed epithelial wound healing and an increased inflammatory response at the site of wounding, possibly due to increased elastase activity (PubMed:11017147, PubMed:25030421). Mutant mice show an increased tendency to die from toxic shock after exposure to bacterial lipopolysaccharide (LPS) (PubMed:12615907). Mutant mice are highly susceptible to M.tuberculosis; all die within 50 days after infection (PubMed:18322212). Mutant mice are highly susceptible infection by L.major. Contrary to what is observed with wild-type, the parasites are not restricted to the initial site of infection, but spread to spleen, liver and bone morrow. The skin lesions at the initial site of infection do not heal normally, but become bigger over time, in parallel with the spread of the parasites. The inflammatory response at the site of infection is more intense and persists longer than normal. Increased protease activity is observed in these lesions and may be the cause of the extensive tissue damage and necrosis (PubMed:25030421).|||Secreted|||Up-regulated by bacterial lipopolysaccharide (PubMed:9039268, PubMed:25030421). Up-regulated in lung after infection with M.tuberculosis (PubMed:18322212). Down-regulated by IFNG (PubMed:9039268). Up-regulated in lung in response to bacterial pneumonia (PubMed:9351627). Up-regulated in macrophages after exposure to L.major (PubMed:25030421). Not up-regulated in spleen in response to bacterial pneumonia (PubMed:9351627). Up-regulated in wounded skin (PubMed:11017147). http://togogenome.org/gene/10090:Tle4 ^@ http://purl.uniprot.org/uniprot/Q3UY41|||http://purl.uniprot.org/uniprot/Q62441 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat Groucho/TLE family.|||Expressed in bone marrow-derived macrophages.|||Homooligomer and heterooligomer with other family members. Interacts with PAX5 (PubMed:10811620). Interacts with LEF1, TCF7, TCF7L1 and TCF7L2 (PubMed:11266540). Interacts with ZNF703; TLE4 may mediate ZNF703 transcriptional repression (PubMed:21317240). Interacts with SIX3 and SIX6 (PubMed:12050133). Interacts with PAX2 (By similarity). Interacts with TLE1 (PubMed:16314515).|||It is uncertain whether Met-1 or Met-8 is the initiator.|||Nucleus|||Phosphorylated. PAX5 binding increases phosphorylation.|||Transcriptional corepressor that binds to a number of transcription factors (PubMed:21317240). Inhibits the transcriptional activation mediated by PAX5, and by CTNNB1 and TCF family members in Wnt signaling (PubMed:10811620). The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression (PubMed:12050133). Involved in transcriptional repression of GNRHR and enhances MSX1-mediated transcriptional repression of CGA/alpha-GSU (PubMed:23371388).|||Ubiquitinated by XIAP/BIRC4.|||WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain. http://togogenome.org/gene/10090:4930402K13Rik ^@ http://purl.uniprot.org/uniprot/B1AW18|||http://purl.uniprot.org/uniprot/Q9D5P7 ^@ Similarity ^@ Belongs to the FAM47 family. http://togogenome.org/gene/10090:Shpk ^@ http://purl.uniprot.org/uniprot/Q9D5J6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Acts as a modulator of macrophage activation through control of glucose metabolism.|||Belongs to the FGGY kinase family.|||Cytoplasm|||Up-regulated by IL-4 and IL-13. Down-regulated by LPS. http://togogenome.org/gene/10090:Recql ^@ http://purl.uniprot.org/uniprot/E9Q3N0|||http://purl.uniprot.org/uniprot/Q3UUK0|||http://purl.uniprot.org/uniprot/Q9Z129 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the helicase family. RecQ subfamily.|||DNA helicase that may play a role in the repair of DNA that is damaged by ultraviolet light or other mutagens. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction.|||Expressed in all tissues examined.|||Interacts with EXO1. Interacts with MLH1.|||Nucleus|||Only expressed in spermatocytes. Expression increases at pachytene (17 days old) and decreases after completion of meiosis II (7 weeks old). http://togogenome.org/gene/10090:Tmbim1 ^@ http://purl.uniprot.org/uniprot/Q3U717|||http://purl.uniprot.org/uniprot/Q8BJZ3 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BI1 family.|||Belongs to the BI1 family. LFG subfamily.|||Due to non-canonical splice donor and acceptor sites.|||Endosome membrane|||Expressed in most tissues except spleen, thymus and testis.|||Lysosome membrane|||Membrane|||Mice (older than 14 months) are prone to aortic dilation as well as cystic medial degeneration (CMD).|||Negatively regulates aortic matrix metalloproteinase-9 (MMP9) production and may play a protective role in vascular remodeling. http://togogenome.org/gene/10090:Gpr19 ^@ http://purl.uniprot.org/uniprot/Q61121 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Tmx4 ^@ http://purl.uniprot.org/uniprot/Q8C0L0 ^@ Subcellular Location Annotation ^@ Nucleus inner membrane http://togogenome.org/gene/10090:Klra10 ^@ http://purl.uniprot.org/uniprot/Q9R1G6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cdc6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J145|||http://purl.uniprot.org/uniprot/O89033 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDC6/cdc18 family.|||Cytoplasm|||Interacts with PCNA, ORC1, cyclin-CDK (By similarity). Interacts with HUWE1 (By similarity). Interacts with ANKRD17 (By similarity). Interacts with GRWD1; origin binding of GRWD1 is dependent on CDC6 (By similarity). Interacts with CDT1; are mutually dependent on one another for loading MCM complexes onto chromatin (By similarity). Interacts with TTC4 (By similarity). Interacts (via Cy motif) with CCNF; the interaction takes place during G2 and M phase (By similarity). Interacts with CDH1 (By similarity).|||Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.|||Nucleus|||Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase complex. http://togogenome.org/gene/10090:P3h2 ^@ http://purl.uniprot.org/uniprot/Q8CG71 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the leprecan family.|||Contradictory results have been described and may be due to differences in the methods used for gene disruption (PubMed:24368846, PubMed:25645914). No visible phenotype, but decreased 3-hydroxyproline formation in collagen COL4A1 and COL1A1 (PubMed:25645914). Full embryonic lethality; the vast majority die before 8.5 dpc (PubMed:24368846). The embryos appear normal, but are surrounded by maternal platelet aggregates and blood clots that form at about 6.5 dpc, resulting in embryonic death (PubMed:24368846). Maternal platelet aggregation is triggered by interaction between maternal Gp6 and embryonic type IV collagen that lacks 3-hydroxyproline (PubMed:24368846). Likewise, pregnant females deficient for Gp6 and P3h2 that bear embryos deficient in P3h2 and heterozygous for Gp6 do not produce any live offspring (PubMed:24368846). In contrast, mutant mice deficient in Gp6 and P3h2 are born at the expected Mendelian rate and have no visible phenotype (PubMed:24368846).|||Detected in kidney (PubMed:25645914). Detected on kidney tubular cells, pancreas acinar cells, Schwann cells of the peripheral nerve in the pinna, and in tunica adventitia, the smooth muscle layer of the aortic wall (at protein level) (PubMed:18487197). Detected in lung, skeletal muscle and kidney (PubMed:18487197). Detected in kidney glomeruli and in prehypertrophic regions of long bone from neonates (PubMed:25645914). In the eye, detected in the epithelial layer of the cornea and at lower levels in the sclera at the posterior end of the eye (PubMed:25645914).|||Endoplasmic reticulum|||Golgi apparatus|||Prolyl 3-hydroxylase that catalyzes the post-translational formation of 3-hydroxyproline on collagens (PubMed:24368846, PubMed:25645914). Contributes to proline 3-hydroxylation of collagen COL4A1 and COL1A1 in tendons, the eye sclera and in the eye lens capsule (PubMed:25645914). Has high activity with the type IV collagen COL4A1, and lower activity with COL1A1. Catalyzes hydroxylation of the first Pro in Gly-Pro-Hyp sequences where Hyp is 4-hydroxyproline. Has no activity on substrates that have proline instead of 4-hydroxyproline in the third position (By similarity).|||Sarcoplasmic reticulum http://togogenome.org/gene/10090:H2-Q7 ^@ http://purl.uniprot.org/uniprot/E9PWT4|||http://purl.uniprot.org/uniprot/L7N260|||http://purl.uniprot.org/uniprot/P14429 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin).|||Involved in the presentation of foreign antigens to the immune system.|||Membrane http://togogenome.org/gene/10090:Caprin1 ^@ http://purl.uniprot.org/uniprot/Q60865 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ability to mediate liquid-liquid phase separation is regulated by ATP: moderate concentrations of ATP enhance phase separation, whereas high concentrations of ATP lead to inhibition of phase separation.|||Belongs to the caprin family.|||Cytoplasmic ribonucleoprotein granule|||Highest expression in thymus, spleen and brain (at protein level). Lower levels in kidney, muscle and liver (at protein level).|||May form homomultimers (PubMed:14764709). Interacts with G3BP1; interaction is direct and promotes stress granule formation (PubMed:17210633). Interacts with G3BP2; interaction is direct and promotes stress granule formation (By similarity). Interacts with PQBP1 (By similarity). Interacts with DDX3X (By similarity). Interacts (when phosphorylated by EPHA4) with FMR1; interaction with FMR1 promotes formation of a membraneless compartment (By similarity).|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. O-glycosylation by OGT inhibit ability to undergo liquid-liquid phase separation (LLPS).|||The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors. CAPRIN1 molecules in the condensed phase are neutral. mRNA-binding promotes phase separation. Moderate concentrations of ATP enhance phase separation by reducing the electrostatic potential of CAPRIN1, thereby promoting intermolecular interactions. In contrast, high concentrations of ATP invert the electrostatic potential of CAPRIN1, so that CAPRIN1 molecules become negatively charged, lead to inhibition of phase separation.|||Tyrosine phosphorylation by EPHA4 promotes interaction with FMR1 and liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors.|||Up-regulated when resting T- or B-lymphocytes or hemopoietic progenitors are activated. Down-regulated when a monocytic leukemia cell line, M1, is induced to differentiate. Expressed in brain at 17.5 dpc (at protein level).|||cytosol|||dendrite|||lamellipodium|||mRNA-binding protein that acts as a regulator of mRNAs transport, translation and/or stability, and which is involved in synaptic plasticity in neurons and cell proliferation and migration in multiple cell types (PubMed:20516077). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (By similarity). Undergoes liquid-liquid phase separation following phosphorylation and interaction with FMR1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (By similarity). In these cytoplasmic ribonucleoprotein granules, CAPRIN1 mediates recruitment of CNOT7 deadenylase, leading to mRNA deadenylation and degradation (By similarity). Binds directly and selectively to MYC and CCND2 mRNAs (By similarity). In neuronal cells, directly binds to several mRNAs associated with RNA granules, including BDNF, CAMK2A, CREB1, MAP2, NTRK2 mRNAs, as well as to GRIN1 and KPNB1 mRNAs, but not to rRNAs (By similarity). http://togogenome.org/gene/10090:Myo7a ^@ http://purl.uniprot.org/uniprot/A0A0R4J113|||http://purl.uniprot.org/uniprot/P97479|||http://purl.uniprot.org/uniprot/Q5MJ56 ^@ Caution|||Developmental Stage|||Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cytoplasm|||Defects in Myo7a are the cause of the shaker-1 (sh-1) phenotype which affects only the inner ear. Sh-1 homozygote mutants show hyperactivity, head tossing and circling due to vestibular dysfunction, together with typical neuroepithelial-type cochlear defects involving dysfunction and progressive degeneration of the organ of Corti.|||Detected in mechanosensory stereocilia of cochlea hair cells (at protein level). Expressed in the retina, cochlea, kidney and liver.|||In the inner ear of the 16.5 day old embryo, expressed only in the cochlear and vestibular sensory hair cells. In addition, expression also occurs in the epithelial cells of the small intestine, hepatocytes, and choroidal plexus.|||Might homodimerize in a two headed molecule through the formation of a coiled-coil rod (By similarity). Identified in a complex with USH1C and USH1G (By similarity). Interacts with MYRIP (PubMed:12221080). Interacts with RPE65 (PubMed:21493626). Interacts with CIB2 (By similarity). May interact with CALM (By similarity). Interacts with WHRN (PubMed:15590698). Interacts with PLEKHB1 (via PH domain) (PubMed:15976448). Interacts with PCDH15 (PubMed:16481439). Interacts with TWF2 (PubMed:19774077). Interacts with USH1G (PubMed:21311020). Interacts with MYH9 (PubMed:27331610). Interacts (via MyTH4-FERM domains) with cytoplasmic regions of ADGRV1 and USH2A (PubMed:17567809). Interacts with PDZD7 (via MyTH4-FERM domains) (PubMed:27525485).|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. In the retina, plays an important role in the renewal of the outer photoreceptor disks. Plays an important role in the distribution and migration of retinal pigment epithelial (RPE) melanosomes and phagosomes, and in the regulation of opsin transport in retinal photoreceptors. Mediates intracellular transport of RPE65 in the retina pigment epithelium. In the inner ear, plays an important role in differentiation, morphogenesis and organization of cochlear hair cell bundles. Motor protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing. Involved in hair-cell vesicle trafficking of aminoglycosides, which are known to induce ototoxicity.|||Originally predicted to contain a coiled coil domain but proposed to contain a stable SAH domain instead.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-7 (MYH7).|||Synapse|||The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Bco2 ^@ http://purl.uniprot.org/uniprot/Q3KNZ2|||http://purl.uniprot.org/uniprot/Q99NF1 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the carotenoid oxygenase family.|||Binds 1 Fe(2+) ion per subunit.|||Broad specificity mitochondrial dioxygenase that mediates the asymmetric oxidative cleavage of carotenoids (PubMed:11278918, PubMed:21106934). Cleaves carotenes (pure hydrocarbon carotenoids) such as all-trans-beta-carotene and lycopene as well as xanthophylls (oxygenated carotenoids) such as zeaxanthin, lutein and beta-cryptoxanthin at both the 9,10 and the 9',10' carbon-carbon double bond (PubMed:11278918, PubMed:21106934). Through its function in carotenoids metabolism regulates oxidative stress and the production of important signaling molecules (PubMed:21106934).|||Expressed in small intestine, liver, kidney, testis and less abundantly in spleen, brain, lung, and heart.|||Homozygous knockout mice lacking Bcdo2 develop normally, and both females and males are fertile when raised on standard diet (PubMed:21106934). On a diet supplemented with xanthophylls, knockout mice accumulate derivatives of these xanthophylls in all tested tissues and develop liver steatosis with large lipid droplets in hepatocytes and a significantly increased triacylglyceride content (PubMed:21106934). Accumulated carotenoids impair mitochondrial respiration, induce ROS production and cellular signaling pathways related to oxidative stress (PubMed:21106934).|||Mitochondrion|||Up-regulated by carotenoids. http://togogenome.org/gene/10090:Ly6c1 ^@ http://purl.uniprot.org/uniprot/P0CW02 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Gtf2h3 ^@ http://purl.uniprot.org/uniprot/Q3UZB8|||http://purl.uniprot.org/uniprot/Q8VD76 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFB4 family.|||Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.|||Nucleus|||Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription (By similarity). Interacts with RARA; the interaction requires prior phosphorylation of RARA on 'Ser-369' which then enhances interaction of RARA with CDK7 (PubMed:9230306).|||Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with RARA; the interaction requires prior phosphorylation of RARA on 'Ser-369' which then enhances interaction of RARA with CDK7. http://togogenome.org/gene/10090:Tpcn2 ^@ http://purl.uniprot.org/uniprot/Q8BWC0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) During Ebola virus (EBOV) infection, controls the movement of endosomes containing virus particles and is required by EBOV to escape from the endosomal network into the cell cytoplasm.|||Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.|||Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position (By similarity).|||Homodimer (Probable). Interacts with LRRK2. Interacts with HAX1. Interacts with MTOR; the interaction is required for TPCN2 ATP sensitivity (By similarity). Found in a complex with LSM12, TPCN1 and TPCN2 (By similarity). Interacts with LSM12 (By similarity).|||Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) (PubMed:19387438, PubMed:20495006, PubMed:20547763, PubMed:25144390, PubMed:27231233). Localizes to the lysosomal and late endosome membranes where it regulates organellar membrane excitability, membrane trafficking, and pH homeostasis. Is associated with a plethora of physiological processes, including mTOR-dependent nutrient sensing, skin pigmentation and autophagy (PubMed:25144390, PubMed:23394946, PubMed:23063126). Ion selectivity is not fixed but rather agonist-dependent and under defined ionic conditions, can be readily activated by both NAADP and PI(3,5)P2. As calcium channel, it increases the pH in the lysosomal lumen, as sodium channel, it promotes lysosomal exocytosis (PubMed:32167471). Plays a crucial role in endolysosomal trafficking in the endolysosomal degradation pathway and is potentially involved in the homeostatic control of many macromolecules and cell metabolites (PubMed:25144390, PubMed:19387438, PubMed:20495006, PubMed:20547763, PubMed:23063126, PubMed:23394946, PubMed:32167471). Also expressed in melanosomes of pigmented cells where mediates a Ca(2+) channel and/or PI(3,5)P2-activated melanosomal Na(+) channel to acidify pH and inhibit tyrosinase activity required for melanogenesis and pigmentation (PubMed:27231233). Unlike the voltage-dependent TPCN1, TPCN2 is voltage independent and can be activated solely by PI(3,5)P2 binding. In contrast, PI(4,5)P2, PI(3,4)P2, PI(3)P and PI(5)P have no obvious effect on channel activation (By similarity).|||Late endosome membrane|||Loss of NAADP-mediated calcium release (PubMed:19387438). Mutant mice are highly susceptible to hepatic cholesterol overload, have hyperlipoproteinaemia and liver damage consistent with non-alcoholic fatty liver hepatitis (PubMed:25144390). TPCN1 and TPCN2 double knockouts are viable, fertile, have no obvious morphological abnormalities, and no obvious behavioral defects. After fasting for 3 days, they are less active and endurance performance is reduced by 8.3 fold in contrast to wild-type littermates that show no changes. Two days after re-introduction of food, mutants regain endurance and become as active as before fasting (PubMed:23394946).|||Lysosome membrane|||Melanosome membrane|||N-glycosylated.|||Regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (PubMed:23394946). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine.|||Widely expressed. Highly expressed in macrophages (PubMed:32167471). Expressed in pigmented cells (PubMed:27231233). http://togogenome.org/gene/10090:H2bc21 ^@ http://purl.uniprot.org/uniprot/Q64524 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Zfp410 ^@ http://purl.uniprot.org/uniprot/Q8BKX7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Interacts with CDKN2A/p14ARF.|||Mice are viable and healthy, but display reduced expression of Chd4, leading to rerepression of fetal hemoglobin genes Hbg1 and Hbg2.|||Nucleus|||O-glycosylated. O-GlcNAcylation may occur in response to increasing glucose levels and affect transcription factor activity.|||Sumoylated. Sumoylation increases its half-life, possibly by blocking ubiquitin-mediated degradation.|||The five zinc finger domains are necessary and sufficient to bind to DNA.|||Transcription factor that binds to the sequence motif 5'-CATCCCATAATA-3', and is specifically required to silence expression of fetal hemoglobin in adult erythroid cells (PubMed:33859416). Prevents expression of fetal hemoglobin genes HBG1 and HBG2 through CHD4: acts as a direct transcriptional activator of CHD4, a central component of the NuRD complex that represses transcription of fetal hemoglobin genes HBG1 and HBG2 in erythroid cells (PubMed:33859416). May also activate transcription of matrix-remodeling genes such as MMP1 during fibroblast senescence (By similarity). May activate transcription of the gap junction gene GJC1, perhaps in response to increasing glucose (By similarity). However, recent studies suggest that ZNF410 is dedicated to regulate expression of a single gene: CHD4 (By similarity). http://togogenome.org/gene/10090:Tti2 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSJ1|||http://purl.uniprot.org/uniprot/Q8BGV4|||http://purl.uniprot.org/uniprot/Q8BNA7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the TTI2 family.|||Component of the TTT complex composed of TELO2, TTI1 and TTI2. Interacts with TELO2 and TTI1. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation.|||Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs (By similarity). http://togogenome.org/gene/10090:Zbtb8b ^@ http://purl.uniprot.org/uniprot/Q8CII0 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Crim1 ^@ http://purl.uniprot.org/uniprot/Q9JLL0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in embryo at 11.5 dpc to 17.7 dpc with a maximum between 12.5 and 13.5 dpc.|||Expressed during embryonic development in brain, kidney, spinal chord, testis, lens, vibrissae, pinna, tooth primordia and in specific regions of the CNS. Expressed in adult lens. Displays male-specific expression in the fetal gonads with the strongest expression in the Sertoli cells of developing testis.|||Interacts with BMP4 and BMP7.|||May play a role in CNS development by interacting with growth factors implicated in motor neuron differentiation and survival. May play a role in capillary formation and maintenance during angiogenesis. Modulates BMP activity by affecting its processing and delivery to the cell surface (By similarity).|||Membrane http://togogenome.org/gene/10090:Zfp54 ^@ http://purl.uniprot.org/uniprot/E9PW05 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed at high levels in testis, may also be expressed at low levels in heart, brain, and skeletal muscle.|||Expression is initially maternally contributed, with increased expression at the two-cell stage followed by significant decrease at the 4-cell stage, remaining consistently low through to the morula stage (PubMed:20624068). Elevated expression in early embryonic stage (7 days post coitum (dpc)) with decreased but consistent expression thereafter in whole embryos (PubMed:10384051). Increased expression at 20 dpc in testis, with lower but consistent expression thereafter (PubMed:10384051).|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Itfg2 ^@ http://purl.uniprot.org/uniprot/Q91WI7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose.|||Lysosome membrane|||Part of the KICSTOR complex composed of KPTN, ITFG2, KICS2 and SZT2. SZT2 probably serves as a link between the other three proteins in the KICSTOR complex and may mediate the direct interaction with the GATOR complex via GATOR1. The KICSTOR complex interacts directly with the GATOR1 complex and most probably indirectly with the GATOR2 complex in an amino acid-independent manner. http://togogenome.org/gene/10090:Prl3c1 ^@ http://purl.uniprot.org/uniprot/Q0VBM3|||http://purl.uniprot.org/uniprot/Q9QUN5|||http://purl.uniprot.org/uniprot/Z4YL38 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed exclusively in decidua.|||Secreted http://togogenome.org/gene/10090:Kcnk1 ^@ http://purl.uniprot.org/uniprot/A0A1D5RMH2|||http://purl.uniprot.org/uniprot/O08581 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Cell membrane|||Cell projection|||Cytoplasmic vesicle|||Detected at very low levels in the embryonic central nervous system (PubMed:9559671, PubMed:18222039). Detected as early as 7 days post conception (PubMed:9559671). Detected in dorsal root ganglia, hippocampus, olfactory epithelia and intestine at 19 dpc (PubMed:18222039). Expression in the brain increases strongly 3-8 days after birth, a period of intense postnatal brain development (PubMed:9559671, PubMed:18222039). Detected in dentate granule cells; expression levels show no significant variability during postnatal development (PubMed:18222039). Expression is higher in adults than in neonates (PubMed:9559671, PubMed:18222039).|||Detected in spiral ganglion neurons (PubMed:17079103). Detected in hippocampus CA1 and CA1 regions and in the molecular layer of the dentate gyrus (PubMed:24368895, PubMed:25406588). Detected on hippocampus astrocytes (PubMed:24368895, PubMed:24496152). Highly expressed in the stria vascularis in the cochlea (PubMed:12855359). Detected in pancreas islet beta cells (PubMed:22431633). Detected in kidney, at brush border membranes in proximal tubules and in cytoplasmic structures in distal convoluted tubules, thick ascending limbs and collecting ducts (at protein level) (PubMed:15540117, PubMed:16025300). Widely expressed. Detected in spiral ganglion cells (PubMed:17079103). Highest expression in brain, kidney, thyroid, salivary gland, adrenal gland, prostate, epididymis, uterus, placenta, colon and jejunum. Moderate expression in eyes, pituitary, pancreas, smooth muscle, testis and ovary. Very low levels in lung, aorta, liver, heart, skeletal muscle, thymus and spleen. In the brain, highest expression in cerebellar granule cells, brainstem, hippocampus and cerebral cortex (PubMed:18222039).|||Endosome|||Homodimer; disulfide-linked (PubMed:9013852). Heterodimer with KCNK2; disulfide-linked (PubMed:24496152). In astrocytes, forms mostly heterodimeric potassium channels with KCNK2, with only a minor proportion of functional channels containing homodimeric KCNK1 (By similarity). Interacts with KCNK3 and KCNK9, forming functional heterodimeric channels (By similarity). Interacts with GNG4 (PubMed:24496152). Identified in a complex with PSD and ARF6; interacts only with PSD that is bound to ARF6 (PubMed:15540117). Interacts with UBE2I (By similarity).|||Inhibited by quinine, quinidine, barium, and internal acidification.|||Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues (PubMed:16847696, PubMed:22431633, PubMed:24368895). Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium. The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (PubMed:9013852, PubMed:24496152). Channel activity is modulated by activation of serotonin receptors (PubMed:24368895). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (PubMed:24496152). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity. Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (By similarity). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (PubMed:25406588). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (PubMed:25406588). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (PubMed:24496152). Required for normal ion and water transport in the kidney (PubMed:16025300). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (PubMed:22431633). The low channel activity of homodimeric KCNK1 may be due to sumoylation. The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (PubMed:15540117).|||Membrane|||No visible phenotype on standard chow, excepting a lower urinary flow rate (PubMed:16025300). Mice appear normal and are fertile (PubMed:24368895). When kept on a low phosphate diet, both wild-type and mutant mice show strongly reduced urinary phosphate secretion. Still, mutant mice display higher fractional urinary phosphate secretion relative to wild-type, leading to reduced inorganic phosphate levels in blood plasma. The impaired phosphate homeostasis seems to be due to indirect effects on the expression of other transporters, such as SLC34A1 and AQP2 (PubMed:16025300). Principal cells from kidney collecting duct are hyperpolarized, display reduced potassium conductance and strongly reduced quinidine-sensitive potassium channel activity (PubMed:16847696). Besides, collecting ducts from mutant mouse kidney display a larger diameter relative to wild-type (PubMed:16847696).|||Perikaryon|||Recycling endosome|||Sumoylation is controversial. Sumoylated by UBE2I. Not sumoylated when expressed in xenopus oocytes or mammalian cells. Sumoylation inactivates the channel, but does not interfere with expression at the cell membrane. Sumoylation of a single subunit is sufficient to silence the dimeric channel. Sumoylation of KCNK1 is sufficient to silence heterodimeric channels formed by KCNK1 and KCNK3 or KCNK9. Desumoylated by SENP1; this activates the channel. Desumoylated by SENP1; this strongly increases halothane-mediated activation of heterodimeric channels formed with KCNK9. SENP1 treatment has no effect.|||Synaptic cell membrane|||Vesicle|||dendrite http://togogenome.org/gene/10090:Or6c6 ^@ http://purl.uniprot.org/uniprot/Q7TRI2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cenps ^@ http://purl.uniprot.org/uniprot/Q9D084 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF9 family. CENP-S/MHF1 subfamily.|||DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage. In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM. In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks. In complex with CENPT, CENPW and CENPX (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression. As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure. DNA-binding function is fulfilled in the presence of CENPX, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own.|||Heterodimer with CENPX, sometimes called MHF; this interaction stabilizes both partners. MHF heterodimers can assemble to form tetrameric structures. MHF also coassemble with CENPT-CENPW heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex. Forms a discrete complex with FANCM and CENPX, called FANCM-MHF; this interaction, probably mediated by direct binding between CENPS and FANCM, leads to synergistic activation of double-stranded DNA binding and strongly stimulates FANCM-mediated DNA remodeling. Recruited by FANCM to the Fanconi anemia (FA) core complex, which consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FAAP24 and FAAP100. The FA core complex associates with Bloom syndrome (BLM) complex, which consists of at least BLM, DNA topoisomerase 3-alpha (TOP3A), RMI1/BLAP75, RPA1/RPA70 and RPA2/RPA32. The super complex between FA and BLM is called BRAFT. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex is probably recruited on centromeres by the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU.|||Nucleus|||centromere|||kinetochore http://togogenome.org/gene/10090:Nup35 ^@ http://purl.uniprot.org/uniprot/Q8R4R6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Nup35 family.|||Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. May play a role in the association of MAD1 with the NPC (By similarity).|||Interacts with TMEM48/NDC1. Forms a complex with NUP93, NUP155, NUP205 and lamin B; The interaction with NUP93 is direct.|||Nucleus membrane|||nuclear pore complex http://togogenome.org/gene/10090:Krt19 ^@ http://purl.uniprot.org/uniprot/B1AQ78|||http://purl.uniprot.org/uniprot/P19001 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Expressed throughout embryonic development with highest levels at 8.5 dpc. Expression decreases by 11.5 dpc and increases again by 17.5 dpc.|||Heterotetramer of two type I and two type II keratins. Interacts with PNN and the actin-binding domain of DMD (By similarity).|||Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||This keratin differs from all other IF proteins in lacking the C-terminal tail domain. http://togogenome.org/gene/10090:Asns ^@ http://purl.uniprot.org/uniprot/Q61024 ^@ Disruption Phenotype ^@ Mice carrying a gene trap insertion in the gene express 20% of the normal level of mRNA. The hypomorphic mutant displays a number of defects that mirror ASNSD syndrome, although the phenotype is milder. Mice have structural brain abnormalities, including reduced cortical thickness and enlarged ventricles. Mutant mice also show deficits in learning and memory. Mutant mice do not show abnormal motor activity or seizure activity. http://togogenome.org/gene/10090:Thbs2 ^@ http://purl.uniprot.org/uniprot/Q03350 ^@ Function|||Similarity|||Subunit ^@ Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Ligand for CD36 mediating antiangiogenic properties.|||Belongs to the thrombospondin family.|||Homotrimer; disulfide-linked. Can bind to fibrinogen, fibronectin, laminin and type V collagen (By similarity). Interacts (via the TSP type I repeats) with CD36; the interaction conveys an antiangiogenic effect. Interacts (via the TSP type I repeats) with HRG; the interaction blocks the antiangiogenic effect of THBS2 with CD36. Can bind to fibrinogen, fibronectin, laminin. http://togogenome.org/gene/10090:Gm16451 ^@ http://purl.uniprot.org/uniprot/D3YZG3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arpc2 ^@ http://purl.uniprot.org/uniprot/Q9CVB6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. Seems to contact the mother actin filament. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Belongs to the ARPC2 family.|||Cell projection|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC (By similarity). Interacts with SHANK3; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex (PubMed:24153177). Interacts with DNAI3; this interaction reduces binding of the Arp2/3 complex to the VCA domain of nucleation promoting factors (By similarity).|||Expressed in hippocampal neurons (at protein level).|||Nucleus|||cytoskeleton|||synaptosome http://togogenome.org/gene/10090:Klk1b4 ^@ http://purl.uniprot.org/uniprot/P00757 ^@ Caution|||Cofactor|||PTM|||Similarity|||Subunit ^@ 7S nerve growth factor is composed of two alpha chains, a beta dimer composed of identical chains, and two gamma chains.|||Belongs to the peptidase S1 family. Kallikrein subfamily.|||Binds 2 Zn(2+) ions per 7S complex. The Zn(2+) ions are bound at the alpha-gamma interfaces.|||Has no demonstrable enzymatic activity. This may be due to several critical changes in its sequence, relative to those of related proteases.|||The presence of Gln-24 prevents cleavage of the activation peptide, which remains attached at the amino end of the mature alpha chain. http://togogenome.org/gene/10090:Vmn1r127 ^@ http://purl.uniprot.org/uniprot/K7N6J5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc13a4 ^@ http://purl.uniprot.org/uniprot/Q8BZ82 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.|||Membrane http://togogenome.org/gene/10090:Bmp8b ^@ http://purl.uniprot.org/uniprot/P55105 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Absence of primordial germ cells, short or missing allantois.|||Belongs to the TGF-beta family.|||By feeding with high-fat diet and cold exposure. By beta-3-adrenergic receptor activation and thyroid hormone treatment.|||Expressed during specific stages of spermatogenesis, with highest levels in stage 6-8 round spermatids after 3 weeks of age.|||Expressed in testis. Expressed in decidual cells of the uterus and in trophoblast cells of the labyrinthine region of the placenta and in the inner root sheath of hair follicles of early postnatal skin. Expressed in the extraembryonic ectoderm in pregastrula and gastrula stage mouse embryos. Expressed in brown adipose tissue and brain.|||Homodimer; disulfide-linked.|||Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity). Involved in the generation of primordial germ cells; this function involves Bmp4 in a synergistic manner though separate receptor complexes seem to be involved. Required for the initiation and maintenance of spermatogenesis. Signaling protein involved in regulation of thermogenesis and energy balance. Proposed to increase the peripheral response of brown adipose tissue (BAT) to adrenergic stimulation while acting centrally in the hypothalamus to increase sympathetic output to BAT.|||Secreted http://togogenome.org/gene/10090:Or6c33 ^@ http://purl.uniprot.org/uniprot/Q8VFU5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ugt1a9 ^@ http://purl.uniprot.org/uniprot/Q62452 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||Endoplasmic reticulum membrane|||Highly expressed in liver and at lower levels in stomach and kidney.|||Homodimer. Homooligomer. Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A10 to form heterodimers.|||UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone. Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties. Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II. Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan. Also metabolizes mycophenolic acid, an immunosuppressive agent. http://togogenome.org/gene/10090:Nlrp4f ^@ http://purl.uniprot.org/uniprot/L7N1W9 ^@ Similarity ^@ Belongs to the NLRP family. http://togogenome.org/gene/10090:Tshz1 ^@ http://purl.uniprot.org/uniprot/Q5DTH5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the teashirt C2H2-type zinc-finger protein family.|||From 12.5 dpc, expressed in the mesenchyme of the developing middle ear, within areas surrounding the condensing malleus and tympanic ring and on both sides of the external acoustic meatus. At 12.5 dpc, borders and surrounds the future cartilages, but excluded from cartilaginous condensations. Not detected in mesenchymal cells in proximal ureters at 14 dpc.|||Interacts (via homeobox domain) with APBB1 (via PID domain 1).|||Normal Mendelian ratio at birth, but none of the mutant animals survive beyond P0. Newborn mutant mice exhibit a strong defect of the soft palate, vertebral malformations in the cervical and thoracic regions of the axial skeleton and malformations in the middle ear components.|||Nucleus|||Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential). http://togogenome.org/gene/10090:Med24 ^@ http://purl.uniprot.org/uniprot/Q99K74 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mediator complex subunit 24 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity). Required for basal and activator-dependent transcription.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with AR (By similarity). Interacts with MED1 and MED10.|||Expressed in the adrenal gland, brain, epididymis, heart, kidney, liver, ovary, pancreas, prostate, skeletal muscle, small intestine, spleen, stomach, testis and thymus.|||Expressed throughout development; expression levels drop immediately after birth. Strongly expressed throughout the primitive nervous system, the hepatic primoridium and the earliest limb buds.|||Nucleus http://togogenome.org/gene/10090:Sqor ^@ http://purl.uniprot.org/uniprot/Q9R112 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SQRD family.|||Binds 1 FAD per subunit.|||Catalyzes the oxidation of hydrogen sulfide with the help of a quinone, such as ubiquinone-10, giving rise to thiosulfate and ultimately to sulfane (molecular sulfur) atoms. Requires an additional electron acceptor; can use sulfite, sulfide or cyanide (in vitro). It is believed the in vivo electron acceptor is glutathione.|||Mitochondrion http://togogenome.org/gene/10090:H2ax ^@ http://purl.uniprot.org/uniprot/P27661 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-6 (H2AXK5ac) by KAT5 component of the NuA4 histone acetyltransferase complex promotes NBN/NBS1 assembly at the sites of DNA damage (By similarity). Acetylation at Lys-37 increases in S and G2 phases (PubMed:20488183, PubMed:7217105). This modification has been proposed to be important for DNA double-strand break repair (PubMed:20488183).|||Belongs to the histone H2A family.|||Chromosome|||Haploinsufficient for the suppression of genomic instability. This phenotype is further exacerbated in the absence of TP53.|||Monoubiquitination of Lys-120 (H2AXK119ub) by RING1 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events (By similarity).|||Most abundant in testis, thymus and spleen.|||Nucleus|||Phosphorylated on Ser-140 (to form gamma-H2AX or H2AX139ph) in response to DNA double strand breaks (DSBs) generated by exogenous genotoxic agents, by stalled replication forks, by meiotic recombination events and during immunoglobulin class switching in lymphocytes. Phosphorylation can extend up to several thousand nucleosomes from the actual site of the DSB and may mark the surrounding chromatin for recruitment of proteins required for DNA damage signaling and repair. Widespread phosphorylation may also serve to amplify the damage signal or aid repair of persistent lesions. Phosphorylation of Ser-140 (H2AX139ph) in response to ionizing radiation is mediated by both ATM and PRKDC while defects in DNA replication induce Ser-140 phosphorylation (H2AX139ph) subsequent to activation of ATR and PRKDC. Dephosphorylation of Ser-140 by PP2A is required for DNA DSB repair. In meiosis, Ser-140 phosphorylation (H2AX139ph) first occurs at synaptonemal complexes during leptotene and is an ATM-dependent response to the formation of programmed DSBs by SPO11. Ser-140 phosphorylation (H2AX139ph) subsequently occurs at unsynapsed regions of both autosomes and the XY bivalent during zygotene and is ATR- and BRCA1-dependent. Ser-140 phosphorylation (H2AX139ph) may also be required for transcriptional repression of unsynapsed chromatin and meiotic sex chromosome inactivation (MSCI), whereby the X and Y chromosomes condense in pachytene to form the heterochromatic XY-body. During immunoglobulin class switch recombination in lymphocytes, Ser-140 phosphorylation (H2AX139ph) at sites of DNA-recombination requires the activation-induced cytidine deaminase AICDA. Phosphorylation at Tyr-143 (H2AXY142ph) by BAZ1B/WSTF determines the relative recruitment of either DNA repair or pro-apoptotic factors. Phosphorylation at Tyr-143 (H2AXY142ph) favors the recruitment of APBB1/FE65 and pro-apoptosis factors such as MAPK8/JNK1, triggering apoptosis. In contrast, dephosphorylation of Tyr-143 by EYA proteins (EYA1, EYA2, EYA3 or EYA4) favors the recruitment of MDC1-containing DNA repair complexes to the tail of phosphorylated Ser-140 (H2AX139ph).|||Synthesized in G1 as well as in S-phase.|||The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with numerous proteins required for DNA damage signaling and repair when phosphorylated on Ser-140. These include MDC1, BRCA1 and the MRN complex, composed of MRE11, RAD50, and NBN. Interaction with the MRN complex is mediated at least in part by NBN. Also interacts with DHX9/NDHII when phosphorylated on Ser-140 and MCPH1 when phosphorylated at Ser-140 or Tyr-143. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with WRAP53/TCAB1 (By similarity). Interacts with TP53BP1 (PubMed:12697768). Interacts with HDGFL2 (By similarity).|||Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Required for checkpoint-mediated arrest of cell cycle progression in response to low doses of ionizing radiation and for efficient repair of DNA double strand breaks (DSBs) specifically when modified by C-terminal phosphorylation. http://togogenome.org/gene/10090:Strada ^@ http://purl.uniprot.org/uniprot/Q3UUJ4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.|||Cytoplasm|||Nucleus|||Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation (By similarity).|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Dlg1 ^@ http://purl.uniprot.org/uniprot/E9Q9H0|||http://purl.uniprot.org/uniprot/H7BWY4|||http://purl.uniprot.org/uniprot/Q3UP61|||http://purl.uniprot.org/uniprot/Q811D0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the MAGUK family.|||Cell junction|||Cytoplasm|||Endoplasmic reticulum membrane|||Essential multidomain scaffolding protein required for normal development. Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels (By similarity). Functional regulator of Kv1.5 channel (By similarity). May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497).|||Expressed in the brain (at protein level) (PubMed:23676497). Expressed in the outer limiting membrane and outer plexiform layer in the retina (at protein level) (PubMed:16519681). Expressed in epithelial, mesenchymal, neuronal, endothelial and hematopoietic cells during embryogenesis. Expressed in fibroblasts and T-cells. Widely expressed in adult mice.|||Homotetramer (Probable). Interacts (via guanylate kinase-like domain) with DLGAP1, DLGAP2, DLGAP3, DLGAP4, and MAP1A (By similarity). Interacts (via guanylate kinase-like domain) with KIF13B (By similarity). May interact with HTR2A (PubMed:14988405). Interacts (via PDZ domains) with GRIA1 (By similarity). Interacts (via PDZ domains) with GRIN2A (By similarity). Interacts (via PDZ domains) with KCND2 and KCND3 (By similarity). Interacts (via PDZ domains) with KCNA1, KCNA2, KCNA3, KCNA4, and ADGRA3 (By similarity). Interacts with KCNF1 (By similarity). Interacts with CAMK2 (By similarity). Interacts with cytoskeleton-associated protein EPB41 (By similarity). Interacts with cytoskeleton-associated protein EZR (PubMed:8922391). Found in a complex with KCNA5 and CAV3 (PubMed:15277200). Found in a complex with APC and CTNNB1 (PubMed:8638125). Interacts (via PDZ domains) with APC (By similarity). Interacts with CDH1 through binding to PIK3R1 (By similarity). Forms multiprotein complexes with CASK, LIN7A, LIN7B, LIN7C, APBA1, and KCNJ12 (By similarity). Interacts with TOPK (By similarity). Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C) (By similarity). May interact with TJAP1 (By similarity). Interacts with PTEN (By similarity). Interacts with LRFN1, LRFN2, LRFN4 and SFPQ (By similarity). Interacts with FRMPD4 (via C-terminus) (By similarity). Interacts (via PDZ domains) with ADGRA2 (via PDZ-binding motif) (PubMed:25558062). Interacts with ADAM10; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (PubMed:23676497). Interacts with DGKI (via PDZ-binding motif) (By similarity). Interacts (via PDZ domains) with MARCHF2 (via PDZ domain); the interaction leads to DLG1 ubiqtuitination and degradation (By similarity). Interacts (via N-terminus) with MPP3; this interaction connects CADM1 with DLG1 and links CADM1 with the regulatory subunit of phosphoinositide-3-kinase (PI3K) by forming a multiprotein complex and participates in cell spreading (PubMed:16519681).|||Membrane|||Mice have craniofacial abnormalities as well as a cleft palate. They are smaller than heterozygous littermates, unable to feed and die within 24 hours of birth.|||Phosphorylated by MAPK12. Phosphorylation of Ser-232 regulates association with GRIN2A (By similarity).|||Postsynaptic density|||Synapse|||The L27 domain may regulate DLG1 self-association. The N-terminal alternatively spliced region is capable of binding several SH3 domains and also moderates the level of protein oligomerization (By similarity).|||The PDZ domains may also mediate association to membranes by binding to EPB41 and ADGRA2 together with the L27 domain that binds CASK and DLG2.|||Ubiquitinated; by MARCHF2 which results in its degradation.|||sarcolemma http://togogenome.org/gene/10090:Adam15 ^@ http://purl.uniprot.org/uniprot/O88839 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Active metalloproteinase with gelatinolytic and collagenolytic activity. Plays a role in the wound healing process. Mediates both heterotypic intraepithelial cell/T-cell interactions and homotypic T-cell aggregation. Inhibits beta-1 integrin-mediated cell adhesion and migration of airway smooth muscle cells. Suppresses cell motility on or towards fibronectin possibly by driving alpha-v/beta-1 integrin (ITAGV-ITGB1) cell surface expression via ERK1/2 inactivation. Cleaves E-cadherin in response to growth factor deprivation. Plays a role in glomerular cell migration (By similarity). Plays a role in pathological neovascularization. May play a role in cartilage remodeling. May be proteolytically processed, during sperm epididymal maturation and the acrosome reaction. May play a role in sperm-egg binding through its disintegrin domain. Interactions with egg membrane could be mediated via binding between the disintegrin-like domain to one or more integrin receptors on the egg.|||At 13.5 dpc, strongly expressed in the developing vasculature of the endocardium. At P17, expressed throughout the retina (at protein level). At 9.5 dpc and thereafter, prominently expressed in the vasculature, including in ventral and dorsal aorta and the caudal artery. In developing heart, detected in endocardium and blood vessels of the ventricle, bulbus arteriosus, and atrium. Also highly expressed in hypertrophic cells of the developing bone. In adult, expressed prominently in brain, including in hippocampus, cerebellum, pons, thalamus, cortex, and olfactory bulb.|||Binds 1 zinc ion per subunit.|||By hypoxic stimulus in retina (at protein level). Up-regulated by VEGF in retina.|||Disintegrin domain binds to integrin alphaV-beta3.|||Endomembrane system|||Expressed moderately in pericytes of retina. Expressed in testis and in spermatozoa from the caput, corpus, and cauda epididymis, as well as in non-capacitated and acrosome-reacted sperm (at protein level). Highly expressed in heart, brain, lung, and kidney. Expressed at lower levels in spleen, liver, testis and muscle.|||Interacts specifically with Src family protein-tyrosine kinases (PTKs) (By similarity). Interacts with ITAGV-ITGB3 (vitronectin receptor). Interacts with SH3GL2 and SNX9; this interaction occurs preferentially with ADAM15 precursor, rather than the processed form, suggesting it occurs in a secretory pathway compartment prior to the medial Golgi. Interacts with ITAG9-ITGB1. Interacts with SH3PXD2A (By similarity). Interacts with ITAGV-ITGB1. Interacts with GRB2, HCK, ITSN1, ITSN2, LYN, MAPK1, MAPK3, NCF1, NCK1, nephrocystin, PTK6, SNX33, LCK and SRC (By similarity).|||May be partially sialylated.|||Mice targeted for deletion of the first 27 amino acids of the ADAM15 N-terminal sequence are viable and fertile, showing no major developmental defects and displaying normal mortality or morbidity. These mutant mice, however, exhibit significantly reduced ischemia-induced retinal neovascularization, choroidal neovascularization at rupture sites in Bruch's membrane, and VEGF-induced subretinal neovascularization, and develop significantly smaller tumors following implantation of B16F0 melanoma cells. Aging mutant mice exhibit accelerated development of osteoarthritic lesions in knee joints.|||Phosphorylation increases association with PTKs.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The cytoplasmic domain is required for SH3GL2- and SNX9-binding.|||The precursor is cleaved by a furin endopeptidase. An additional membrane proximal site of cleavage affects a small percentage of the proteins and results in disulfide-linked fragments. The prodomain is apparently cleaved in several positions that are N-terminal of the furin cleavage site.|||acrosome|||adherens junction|||flagellum http://togogenome.org/gene/10090:Prss55 ^@ http://purl.uniprot.org/uniprot/Q14BX2 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Controversial data exist concerning the topology of PRS55. One study in mouse shows that PRSS55 is a GPI-anchored protein (PubMed:30032357). An other study does not confirm the GPI-anchor status of PRSS55 (By similarity). However, as a GPI-anchor motif is detected, the possibility of a GPI-anchor instead of a single-pass type I membrane protein is probable.|||Deficient male display infertility with impaired sperm migration from uterus into oviduct and defective sperm-zona and sperm-egg recognition/binding. However, the mating activity, sperm production, sperm morphology, sperm motility, inducibility of AR, activity of acrosomal enzymes and in vitro sperm fertility are almost normal. Male show an absence of mature ADAM3 in sperm.|||Expressed in adult mouse testis.|||Probable serine protease, which plays a crucial role in the fertility of male mice including sperm migration and sperm-egg interaction (PubMed:30032357).|||acrosome http://togogenome.org/gene/10090:Zfp385a ^@ http://purl.uniprot.org/uniprot/Q8VD12 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc, expressed in large polynucleated cells within the liver. Induced during adipogenesis.|||By p53/TP53 in response to DNA damage.|||Cytoplasm|||Expressed in brain and testis (at protein level). In brain, the expression is located to olfactory bulb, cerebral cortex, hippocampus, satellite cells and Purkinje cells of the cerebellum molecular layer. Detected in bone marrow, white and brown adipose tissue, lung and at lower levels in the thymus.|||Interacts with p53/TP53; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest. Interacts with ELAVL1; the interaction is indirect, mRNA-dependent and may regulate p53/TP53 expression.|||No visible phenotype at birth. Between 2-3 weeks after birth, some lethality is observed, may be due to internal hemorrhaging mainly in brain and gastrointestinal tracts. Surviving mutants are fertile and smaller than their wild-type littermates. Deficiency alters hemostasis which is associated with a block in the formation of alpha-granules in megakaryocytes and abnormal platelet morphology. Mice also exhibit tremor, ataxic gate, tilted head, severe impairments in motor coordination and motor learning related to cerebellar functions. Mice show functional deregulation of adipose tissues, although the total fat mass is not affected. They express lower levels of C/EBP alpha in adipose tissue, have impaired glucose tolerance with high plasma insulin levels and plasma adiponectin levels are significantly lower. Upon genotoxic stress, skin and prostate show increased apoptosis.|||RNA-binding protein that affects the localization and the translation of a subset of mRNA. May play a role in adipogenesis through binding to the 3'-UTR of CEBPA mRNA and regulation of its translation. Targets ITPR1 mRNA to dendrites in Purkinje cells, and may regulate its activity-dependent translation. With ELAVL1, binds the 3'-UTR of p53/TP53 mRNAs to control their nuclear export induced by CDKN2A. Hence, may regulate p53/TP53 expression and mediate in part the CDKN2A anti-proliferative activity. May also bind CCNB1 mRNA. Alternatively, may also regulate p53/TP53 activity through direct protein-protein interaction. Interacts with p53/TP53 and promotes cell-cycle arrest over apoptosis enhancing preferentially the DNA binding and transactivation of p53/TP53 on cell-cycle arrest target genes over proapoptotic target genes. May also regulate the ubiquitination and stability of CDKN1A promoting DNA damage-induced cell cycle arrest. Also plays a role in megakaryocytes differentiation.|||Ubiquitinated upon prolonged exposure to genotoxic stress, which leads to proteasomal degradation of ZNF385A and releases p53/TP53 from cell-cycle arrest target gene promoters.|||dendrite|||nucleolus http://togogenome.org/gene/10090:Adra2a ^@ http://purl.uniprot.org/uniprot/Q01338 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.|||Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2A sub-subfamily.|||Cell membrane|||It is uncertain whether Met-1 or Met-16 is the initiator. http://togogenome.org/gene/10090:Slc13a5 ^@ http://purl.uniprot.org/uniprot/Q67BT3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.|||Cell membrane|||High-affinity sodium/citrate cotransporter that mediates citrate entry into cells, which is a critical participant of biochemical pathways (PubMed:35448538, PubMed:26324167, PubMed:14656221). May function in various metabolic processes in which citrate has a critical role such as energy production (Krebs cycle), fatty acid synthesis, cholesterol synthesis, glycolysis, and gluconeogenesis (PubMed:12826022). Transports citrate into the cell in a Na(+)-dependent manner, recognizing the trivalent form of citrate (physiological pH) rather than the divalent form (PubMed:12826022, PubMed:14656221, PubMed:26324167). Can recognizes succinate as a substrate, but its affinity for succinate is several fold lower than for citrate (PubMed:26324167, PubMed:14656221). The stoichiometry is probably 4 Na(+) for each carboxylate, irrespective of whether the translocated substrate is divalent or trivalent, rendering the process electrogenic (PubMed:26324167, PubMed:14656221). Involved in the regulation of citrate levels in the brain (PubMed:32682952).|||Homodimer.|||Inhibited by Li(+).|||Mice show increased propensity for epileptic seizures, proepileptogenic neuronal excitability changes in the hippocampus, and significant citrate level alterations in the CSF and brain tissue (PubMed:32682952). Null mice show perturbations in fatty acids, bile acids, and energy metabolites in liver, serum, and brain (PubMed:35448538). http://togogenome.org/gene/10090:Fndc9 ^@ http://purl.uniprot.org/uniprot/Q8BJN4 ^@ Caution|||Subcellular Location Annotation ^@ Encoded in intron of the gene CYFIP2 (opposite strand).|||Membrane http://togogenome.org/gene/10090:Rassf5 ^@ http://purl.uniprot.org/uniprot/Q5EBH1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts directly with activated HRAS; a RASSF5-STK4/MST1 complex probably associates with activated HRAS (PubMed:9488663, PubMed:11857081, PubMed:11864565, PubMed:18596699). Interacts with KRAS (PubMed:11857081, PubMed:11864565). Probably interacts with Ras-like GTPases RRAS, MRAS, RAP1B, RAP2A and RALA (PubMed:11857081). Interacts with RRAS2 (By similarity). Can self-associate (PubMed:11857081). Interacts with RSSF1 isoform A (PubMed:11857081). The RSSF1 isoform A-RSSF5 heterodimer probably mediates the association of RSSF1 with HRAS (PubMed:11864565, PubMed:11857081). Isoform 2 interacts with activated RAP1A and ITGAL/LFA-1 (By similarity). Binds STK4/MST1, inhibiting STK4/MST1 autoactivation (PubMed:11864565).|||Potential tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing (By similarity). May be involved in regulation of Ras apoptotic function. The RASSF5-STK4/MST1 complex may mediate HRAS and KRAS induced apoptosis.|||cytoskeleton http://togogenome.org/gene/10090:Ercc3 ^@ http://purl.uniprot.org/uniprot/P49135 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent 3'-5' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.|||Belongs to the helicase family. RAD25/XPB subfamily.|||Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with PUF60. Interacts with ATF7IP. Interacts with KAT2A; leading to KAT2A recruitment to promoters and acetylation of histones.|||Nucleus http://togogenome.org/gene/10090:Or2a14 ^@ http://purl.uniprot.org/uniprot/K9J725 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arl4c ^@ http://purl.uniprot.org/uniprot/P61208 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||Cell membrane|||Cytoplasm|||Interacts with CYTH2. Interacts with alpha tubulin; interaction is independent on the ARL4C GTP or GDP binding status (By similarity).|||Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. May be involved in transport between a perinuclear compartment and the plasma membrane, apparently linked to the ABCA1-mediated cholesterol secretion pathway. Recruits CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane in the GDP-bound form. Regulates the microtubule-dependent intracellular vesicular transport from early endosome to recycling endosome process (By similarity).|||filopodium http://togogenome.org/gene/10090:Ppp6r1 ^@ http://purl.uniprot.org/uniprot/Q7TSI3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAPS family.|||Cytoplasm|||Derived from pre-RNA.|||Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed of the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP6C and NFKBIE. Interacts with ANKRD28, ANKRD44 and ANKRD52 (By similarity).|||Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha (By similarity).|||Ubiquitous with highest expression in lung, spleen and bladder. http://togogenome.org/gene/10090:Prl4a1 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0M4|||http://purl.uniprot.org/uniprot/O35256 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed specifically in placenta. Expressed in both trophoblast giant cells and spongiotrophoblast cells.|||Low level on day 8, abundant on days 10 to 14, and decreases by day 16.|||Secreted http://togogenome.org/gene/10090:Ptprh ^@ http://purl.uniprot.org/uniprot/E9Q0N2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cytoplasm|||Detected from embryonic stage 16.5 dpc onwards, with marked increase in expression level after birth.|||Expressed strongly in the intestinal tract, with particularly high levels in the duodenum and jejunum (at protein level). Also expressed at low level in the testis (at protein level). Not detected in other tissues tested (at protein level).|||Homodimer; disulfide-linked (By similarity). Interacts with LCK (By similarity). Interacts (phosphorylated form) with GRB2 (via SH2 domain) (PubMed:20398064). Interacts (phosphorylated form) with FYN (via SH2 domain) (PubMed:20398064). Interacts (via extracellular domain) with CEACAM20 (via extracellular domain); the interaction dephosphorylates CEACAM20 (PubMed:26195794).|||Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of Jurkat cells (By similarity). Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response (PubMed:26195794).|||Viable and fertile (PubMed:19170756). No significant effect on body weight or nutrient absorption (PubMed:19170756). Morphology of intestinal epithelium cells appears to be normal (PubMed:19170756). Double knockouts with APC heterozygotes, a model for intestinal tumorigenesis, show reduced adenoma growth (PubMed:19170756). Double knockouts with IL10, a model of inflammatory bowel disease, show significantly increased colonic inflammation in the presence of commensal bacteria and reduced survival rates (PubMed:26195794).|||microvillus membrane http://togogenome.org/gene/10090:Tmem151a ^@ http://purl.uniprot.org/uniprot/Q6GQT5 ^@ Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM151 family.|||Endoplasmic reticulum membrane|||Highly expressed in the central nervous system (CNS) including the cerebral cortex, hippocampus, spinal cord, brainstem, and thalamus. Expression is relatively low during postnatal stages but highly expressed at postnatal day 14 (P14), and declined in adulthood. Also expressed in the stomach, heart, liver, spleen, lung, kidney, and muscle.|||Knockout mice exhibited frequent spontaneous dyskinesia attacks.|||axon|||dendrite http://togogenome.org/gene/10090:Des ^@ http://purl.uniprot.org/uniprot/P31001|||http://purl.uniprot.org/uniprot/Q3V1K9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylation prevents ability to form intermediate filaments.|||Belongs to the intermediate filament family.|||Cardiac progenitor cells and immature cardiomyocytes (at protein level).|||Cytoplasm|||Homomer (By similarity). Interacts with MTM1 (By similarity). Interacts with DST (PubMed:10357897). Interacts with tubulin-alpha; specifically associates with detyrosinated tubulin-alpha (PubMed:27102488). Interacts with EPPK1; interaction is dependent of higher-order structure of intermediate filament. Interacts with CRYAB (By similarity). Interacts with NEB (via nebulin repeats 160-164) (By similarity). Interacts (via rod region) with NEBL (via nebulin repeats 1-5) (By similarity). Interacts with ASB2 isoform 1; the interaction targets DES for proteasomal degradation (PubMed:26343497). Interacts with PLEC isoform 1C (PubMed:24940650). Interacts with PKP1 (PubMed:10852826).|||Mice hearts have reduced nebulette (NEB) and elevated actin levels, with intact myofibers showing disordered NEB organization.|||Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (By similarity). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:25394388). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488). Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (PubMed:27733623).|||Nucleus|||Phosphorylation at Ser-7, Ser-28 and Ser-32 by CDK1, phosphorylation at Ser-60 by AURKB and phosphorylation at Thr-76 by ROCK1 contribute to efficient separation of desmin intermediate filaments during mitosis.|||Ubiquitination by a SCF-like complex containing ASB2 isoform 1 leads to proteasomal degradation.|||Z line|||sarcolemma http://togogenome.org/gene/10090:Ttf1 ^@ http://purl.uniprot.org/uniprot/Q62187 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin (PubMed:7720715, PubMed:9267035, PubMed:15292447, PubMed:9049305). Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription (PubMed:15292447, PubMed:20513429). Interaction with BAZ2A/TIP5 recovers DNA-binding activity (PubMed:15292447).|||Nucleus|||Oligomer. The oligomeric structure enables to interact simultaneously with two separate DNA fragments (PubMed:9092622). Interacts with BAZ2A/TIP5 (PubMed:15292447). Interacts with CAVIN1 (PubMed:9582279, PubMed:27528195). Interacts (via the N-terminal region (NRD) and a C-terminal region) with CDKN2A/ARF; the interaction is direct (PubMed:20513429). Interacts (via C-terminal region) with NPM1/B23 (PubMed:20513429).|||The N-terminal region (NRD) inhibits DNA-binding via its interaction with the C-terminal region.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Semp2l2a ^@ http://purl.uniprot.org/uniprot/G3X9P9 ^@ Similarity ^@ Belongs to the peptidase C48 family. http://togogenome.org/gene/10090:Trim40 ^@ http://purl.uniprot.org/uniprot/Q3UWA4 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the TRIM/RBCC family.|||E3 ubiquitin-protein ligase that plays a role in the limitation of the innate immune response. Mediates inhibition of the RLR signaling pathway by ubiquitinating RIGI and IFIH1 receptors, leading to their proteasomal degradation. Promotes also the neddylation of IKBKG/NEMO, stabilizing NFKBIA, and thereby inhibiting of NF-kappa-B nuclear translocation and activation.|||Interacts with NEDD8.|||TRIM40 deficiency greatly enhances antiviral immune responses and interferon-beta production and thus inhibits viral replication. http://togogenome.org/gene/10090:Or5d40 ^@ http://purl.uniprot.org/uniprot/Q7TR25 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or52ae7 ^@ http://purl.uniprot.org/uniprot/E9Q564 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stim2 ^@ http://purl.uniprot.org/uniprot/A5CVE4|||http://purl.uniprot.org/uniprot/P83093 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Glycosylated.|||Membrane|||Oligomer with STIM1. Interacts with ORAI1 (By similarity).|||Phosphorylated predominantly on Ser residues.|||Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx (By similarity). http://togogenome.org/gene/10090:Inhbe ^@ http://purl.uniprot.org/uniprot/O08717 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||First expression in embryonic liver is detected at 17.5 dpc.|||Homodimeric or heterodimeric through association with alpha and beta subunits, linked by one or more disulfide bonds. Inhibins are heterodimers of one alpha and one beta subunit. Activins are homo- or heterodimers of beta subunits only (By similarity).|||Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.|||Secreted http://togogenome.org/gene/10090:Kndc1 ^@ http://purl.uniprot.org/uniprot/Q0KK55 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc, highly expressed in the mid- and hindbrain and only weakly in the forebrain, but during development the main expression shifts towards the telencephalon as seen at 17.5 dpc (PubMed:16099729). In cerebellum expression is highly up-regulated between postnatal days P7 and P12. At P7, low expression levels throughout the brain, but high in hippocampus, thalamus and the cerebellar white matter (PubMed:17984326).|||Highly expressed in the brain and at low levels in the ovary. In the brain it is most prominently expressed in the cerebellum where it is restricted to the granular Purkinje cell layer.|||Interacts (via KIND2) with MAP2; the interaction enhances MAP2 phosphorylation and localizes KNDC1 to dendrites.|||Perikaryon|||RAS-Guanine nucleotide exchange factor (GEF) that controls the negative regulation of neuronal dendrite growth by mediating a signaling pathway linking RAS and MAP2 (PubMed:17984326, PubMed:21385318). May be involved in cellular senescence (By similarity).|||dendrite http://togogenome.org/gene/10090:Cln8 ^@ http://purl.uniprot.org/uniprot/Q542J5|||http://purl.uniprot.org/uniprot/Q9QUK3 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit ^@ Could play a role in cell proliferation during neuronal differentiation and in protection against cell death.|||Defects in Cln8 are the cause of the phenotype motor neuron degeneration (mnd). Mnd is a naturally occurring mutant It is characterized by progressive motor system degeneration. It has intracellular autofluorescent inclusions similar to those seen in human Cln8.|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Interacts with CLN5 (PubMed:19941651). Interacts with CLN3 (By similarity).|||Membrane http://togogenome.org/gene/10090:Mia3 ^@ http://purl.uniprot.org/uniprot/Q8BI84 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although 2 transmembrane domains are predicted, it only contains one transmembrane domain. The other predicted transmembrane region is probably a hairpin-type region embedded into the membrane, which does not cross the membrane. It is unclear which of the 2 predicted transmembrane regions is the transmembrane or the hairpin-type region.|||Belongs to the MIA/OTOR family. Tango1 subfamily.|||Endoplasmic reticulum membrane|||Interacts with MIA2. Interacts (via SH3 domain) with COL7A1. Interacts with the COPII coat subunits SEC23A, SEC23B and maybe SEC24C. May interact with APOB and MIA2. Interacts with SEC16A.|||Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum. Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES.|||The proline-rich domain (PRD) contains repeated PPP motifs. A single PPP motif is necessary and sufficient to mediate interaction with the COPII coat subunits SEC23A and SEC23B.|||Ubiquitously expressed during embryogenesis, starting at 8 dpc. http://togogenome.org/gene/10090:Olfml3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J086|||http://purl.uniprot.org/uniprot/Q8BK62 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the OLFML3 family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||Secreted scaffold protein that plays an essential role in dorsoventral patterning during early development. Stabilizes axial formation by restricting chordin (CHRD) activity on the dorsal side. Acts by facilitating the association between the tolloid proteases and their substrate chordin (CHRD), leading to enhance chordin (CHRD) degradation (By similarity). May have matrix-related function involved in placental and embryonic development, or play a similar role in other physiological processes (By similarity). http://togogenome.org/gene/10090:Phrf1 ^@ http://purl.uniprot.org/uniprot/A6H619 ^@ Sequence Caution|||Subunit ^@ Interacts with POLR2A (via the C-terminal domain).|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:Cfap157 ^@ http://purl.uniprot.org/uniprot/Q0VFX2 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CFAP157 family.|||Expression is activated by FOXJ1.|||Interacts with TUBB and TUBA4A (PubMed:27965440). Interacts with CEP350 (PubMed:27965440).|||Mice were born at expected Mendelian ratios and appear normal but homozygous males are infertile. Spermatozoa display impaired motility due to defects in the axoneme. Sperm cells show an axonemal loop of the midpiece, supernumerary axonemes and a disrupted axonemal arrangement, as well as defective axonemes along the flagella.|||Specifically expressed in tissues containing motile cilia.|||Specifically required during spermatogenesis for flagellum morphogenesis and sperm motility (PubMed:27965440). May be required to suppress the formation of supernumerary axonemes and ensure a correct ultrastructure (PubMed:27965440).|||cilium basal body http://togogenome.org/gene/10090:Rasip1 ^@ http://purl.uniprot.org/uniprot/Q3U0S6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in kidney, heart, skeletal muscle, small intestine and lung.|||Golgi stack|||Interacts with Ras family members that have been activated by GTP binding. Interacts with HRAS, RAP1A, RAP2, RRAS, RAF1 and RRAS2 (By similarity). Interacts with MYH9 and ARHGAP29.|||Required for the proper formation of vascular structures that develop via both vasculogenesis and angiogenesis. Acts as a critical and vascular-specific regulator of GTPase signaling, cell architecture, and adhesion, which is essential for endothelial cell morphogenesis and blood vessel tubulogenesis. Regulates the activity of Rho GTPases in part by recruiting ARHGAP29 and suppressing RhoA signaling and dampening ROCK and MYH9 activities in endothelial cells. May act as effector for Golgi-bound HRAS and other Ras-like proteins. May promote HRAS-mediated transformation. Negative regulator of amino acid starvation-induced autophagy (By similarity).|||Specifically expressed in the endothelium of the developing blood vessels in embryos.|||perinuclear region http://togogenome.org/gene/10090:Gm5460 ^@ http://purl.uniprot.org/uniprot/A0A2I3BRZ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ATR family.|||Membrane http://togogenome.org/gene/10090:Tm7sf3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0K4|||http://purl.uniprot.org/uniprot/Q9CRG1 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Involved in the inhibition of cytokine-induced death of pancreatic beta cells (PubMed:21853325). Involved in the promotion of insulin secretion from pancreatic beta cells (By similarity). Is a downstream transcriptional target of p53/TP53, and acts as a pro-survival homeostatic factor that attenuates the development of cellular stress. Maintains protein homeostasis and promotes cell survival through attenuation of endoplasmic reticulum (ER) stress and the subsequent induction of unfolded protein response (UPR) (PubMed:27740623).|||Membrane http://togogenome.org/gene/10090:Baz2b ^@ http://purl.uniprot.org/uniprot/A2AUY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WAL family.|||Component of the BRF-1 ISWI chromatin remodeling complex, at least composed of SMARCA1 and BAZ2B, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (By similarity). Within the BRF-1 ISWI chromatin remodeling complex interacts with SMARCA1; the interaction is direct (By similarity). Component of the BRF-5 ISWI chromatin remodeling complex, at least composed of SMARCA5/SNF2H and BAZ2B, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (By similarity). Within the BRF-5 ISWI chromatin remodeling complex interacts with SMARCA5/SNF2H; the interaction is direct (By similarity). Interacts with acetylated lysine residues on histone H1.4, H2A, H2B, H3 and H4 (in vitro) (By similarity). Interacts with EHMT1 (PubMed:32103178).|||Nucleus|||Regulatory subunit of the ATP-dependent BRF-1 and BRF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (By similarity). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (By similarity). The BRF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the BRF-5 ISWI chromatin remodeling complex (By similarity). Chromatin reader protein, involved in positively modulating the rate of age-related behavioral deterioration (PubMed:32103178). Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with histone methyltransferase EHMT1 (PubMed:32103178). http://togogenome.org/gene/10090:Il11 ^@ http://purl.uniprot.org/uniprot/P47873 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-6 superfamily.|||Cytokine that stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production (PubMed:8913282). Also promotes the proliferation of hepatocytes in response to liver damage (PubMed:22253262). Binding to its receptor formed by IL6ST and either IL11RA1 or IL11RA2 activates a signaling cascade that promotes cell proliferation, also in the context of various cancers (PubMed:10026196, PubMed:23948300). Signaling leads to the activation of intracellular protein kinases and the phosphorylation of STAT3 (PubMed:23948300, PubMed:22253262). The interaction with the membrane-bound IL11RA and IL6ST stimulates 'classic signaling', whereas the binding of IL11 and soluble IL11RA to IL6ST stimulates 'trans-signaling' (By similarity).|||Interacts with either IL11RA1 or IL11RA2 to associate with IL6ST, giving rise to a multimeric signaling complex.|||Secreted|||Up-regulated in hepatocytes by oxidative stress caused by liver damage. http://togogenome.org/gene/10090:Cysrt1 ^@ http://purl.uniprot.org/uniprot/Q9D1E4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CYSRT1 family.|||Component of the stratum corneum that may contribute to epidermal antimicrobial host defenses.|||Cornified envelope|||Interacts with components of the late cornfied envelope (LCE). http://togogenome.org/gene/10090:Piwil2 ^@ http://purl.uniprot.org/uniprot/Q8CDG1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein TDRD1 and subsequent localization to the meiotic nuage, also named P granule.|||Belongs to the argonaute family. Piwi subfamily.|||Cytoplasm|||Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (PubMed:11578866, PubMed:14736746, PubMed:17446352, PubMed:18381894, PubMed:18922463, PubMed:26669262). During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' PIWIL4 (PubMed:22020280, PubMed:23706823, PubMed:26669262). PIWIL2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded (PubMed:28633017). Required for PIWIL4/MIWI2 nuclear localization and association with secondary piRNAs antisense (PubMed:18381894, PubMed:18922463, PubMed:26669262). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (PubMed:19114715). Indirectly modulates expression of genes such as PDGFRB, SLC2A1, ITGA6, GJA7, THY1, CD9 and STRA8 (PubMed:16261612). Represses circadian rhythms by promoting the stability and activity of core clock components BMAL1 and CLOCK by inhibiting GSK3B-mediated phosphorylation and ubiquitination-dependent degradation of these proteins (PubMed:28903391).|||Expressed from 12.5 dpc until adult in male gonads. In female gonads, detected since 12.5 dpc, then begins to cease after birth and disappears until the development of adult ovary (PubMed:11578866). Highly expressed in embryonic male germ cells at embryonic day 16.5 and expression decreases by postnatal day 2.5 (PubMed:32381626).|||Expressed in adult testis, specifically in spermatocytes and in spermatogonia (PubMed:11279525, PubMed:11578866, PubMed:12906857, PubMed:18404146, PubMed:18922463, PubMed:19114715, PubMed:19377467, PubMed:28903391). Only detected in primordial germ cells of both sexes. Widely expressed in tumors. Also present at early stages of oocyte growth. Present in the mitotic spermatogonia (PubMed:23706823). Not detected in the first stages of meiosis (preleptotene and leptotene) (PubMed:23706823). Detected at the late zygotene stage and increases throughout pachytene, declining from this stage onward until expression stops at the early round spermatid stage (at protein level) (PubMed:23706823).|||Interacts with DDX4, MAEL, EIF3A, EIF4E, EIF4G, PRMT5 and WDR77. Associates with EIF4E- and EIF4G-containing m7G cap-binding complexes. Interacts (when methylated on arginine residues) with TDRD1 and TDRKH/TDRD2. Interacts with TDRD12 (PubMed:24067652). Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs (PubMed:26669262). Interacts with MOV10L1 (PubMed:20534472, PubMed:20547853). Interacts with GPAT2 (PubMed:23611983). Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886). Interacts (via PIWI domain) with BMAL1 and CLOCK (PubMed:28903391). Interacts with GSK3B (PubMed:28903391). Interacts with TEX15 (PubMed:32381626).|||Mice exhibit blocked spermatogenesis at the early prophase of the first meiosis due to transposable elements derepression, and apoptosis occurs subsequently. Female mice are fertile, while male are sterile. http://togogenome.org/gene/10090:Macroh2a2 ^@ http://purl.uniprot.org/uniprot/Q8CCK0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Nucleus|||Present in liver, kidney and adrenal gland (at protein level). In the liver, present in cells of the bile ducts and parenchymal cells, but not in hepatocytes. In the kidney, present in proximal and distal convoluted tubules and in glomeruli. Present at highest levels in the parietal layer of Bowman capsule. In the adrenal gland, present in the outer cells of the capsule.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers.|||Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in stable X chromosome inactivation. http://togogenome.org/gene/10090:Sstr4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1D6|||http://purl.uniprot.org/uniprot/P49660 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. http://togogenome.org/gene/10090:Usp1 ^@ http://purl.uniprot.org/uniprot/Q8BJQ2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autocatalytic cleavage of USP1 following UV irradiation inactivates it, leading to an increase in ubiquitinated PCNA, recruitment of POLH and translesion synthesis.|||Belongs to the peptidase C19 family.|||Interacts with FANCD2 and PCNA. Interacts with WDR48. Interacts with ATAD5; the interaction regulates USP1-mediated PCNA deubiquitination.|||Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2. Also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity.|||Nucleus|||Ubiquitinated by the CRL2(KLHDC2) complex following autocatalytic cleavage, leading to its degradation: the CRL2(KLHDC2) complex recognizes the diglycine (Gly-Gly) at the C-terminus. http://togogenome.org/gene/10090:Apol9b ^@ http://purl.uniprot.org/uniprot/Q8C7I4 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Tcaf3 ^@ http://purl.uniprot.org/uniprot/Q6QR59 ^@ Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the TCAF family.|||May act as an autoantigen in prostate autoimmunity.|||May play a role in the regulation of the cation channel TRPM8 activity.|||Prostate-specific. Present in both dorso-lateral and anterior prostate. http://togogenome.org/gene/10090:H2bc24 ^@ http://purl.uniprot.org/uniprot/P10853|||http://purl.uniprot.org/uniprot/Q8CBB6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Fam219a ^@ http://purl.uniprot.org/uniprot/A2ANP1|||http://purl.uniprot.org/uniprot/Q9D772 ^@ Similarity ^@ Belongs to the FAM219 family. http://togogenome.org/gene/10090:Nat8f2 ^@ http://purl.uniprot.org/uniprot/Q8CHQ9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||Membrane|||Probable acetyltransferase (Probable). Has no detectable histone acetyltransferase activity towards histone H3 or H4. http://togogenome.org/gene/10090:Dele1 ^@ http://purl.uniprot.org/uniprot/Q9DCV6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DELE1 family.|||Interacts (via TPR repeats) with EIF2AK1/HRI; activating the protein kinase activity of EIF2AK1/HRI, thereby promoting the integrated stress response (ISR).|||Interacts with DAP3.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Protein kinase activator generated by protein cleavage in response to mitochondrial stress, which accumulates in the cytosol and specifically binds to and activates the protein kinase activity of EIF2AK1/HRI. It thereby activates the integrated stress response (ISR): EIF2AK1/HRI activation promotes eIF-2-alpha (EIF2S1) phosphorylation, leading to a decrease in global protein synthesis and the induction of selected genes, including the transcription factor ATF4, the master transcriptional regulator of the ISR.|||Protein kinase activator that activates the ISR in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting DELE1 localization at the mitochondrial surface, where it binds and activates EIF2AK1/HRI to trigger the ISR.|||Protein kinase activator that acts as a key activator of the integrated stress response (ISR) following various stresses, such as iron deficiency and mitochondrial stress. Detects impaired protein import and processing in mitochondria, activating the ISR. May also required for the induction of death receptor-mediated apoptosis through the regulation of caspase activation.|||The TPR repeats bind to and activate EIF2AK1/HRI.|||Unstable protein in absence of stress: imported in the mitochondrial matrix following processing by the mitochondrial-processing peptidase (MPP), where it is degraded by LONP1. Stabilized in response to iron deficiency: iron deficiency impairs mitochondrial import, promoting localization at the mitochondrial surface and stabilization. Cleaved by OMA1 in response to mitochondrial stress, generating the DAP3-binding cell death enhancer 1 short form (DELE1(S) or S-DELE1) that accumulates in the cytosol and activates the protein kinase activity of EIF2AK1/HRI. Protein cleavage by OMA1 can take place at different positions, and apparently does not require a specific sequence motif.|||cytosol http://togogenome.org/gene/10090:Khdrbs3 ^@ http://purl.uniprot.org/uniprot/Q9R226 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the KHDRBS family.|||Highly expressed in testis and brain. In adult cerebellum expressed predominantly in internal granular layer interneurons and in hippocampus is exclusively expressed in CA neurons; expression is restricted to neuronal subpopulations largely non-overlapping with expression of KHDRBS2/SLM-1.|||In the developing cerebellum expression is decreasing in the first 3 postnatal weeks.|||Nucleus|||Phosphorylated on tyrosine residues by PTK6.|||RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds preferentially to the 5'-[AU]UAAA-3' motif in vitro (PubMed:19457263). Binds optimally to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides (By similarity). Binds poly(A). RNA-binding abilities are down-regulated by tyrosine kinase PTK6 (PubMed:15471878). Involved in splice site selection of vascular endothelial growth factor (By similarity). In vitro regulates CD44 alternative splicing by direct binding to purine-rich exonic enhancer (By similarity). Can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners such as neuroligins and LRRTM family members. High concentrations in forebrain structures block splicing inclusion of NRXN1-3 AS4 exons while low concentrations favor their inclusion. Targeted, cell-type specific splicing regulation of NRXN1 at AS4 is involved in neuronal glutamatergic synapse function and plasticity and is linked to behavioral aspects (PubMed:22196734, PubMed:23637638, PubMed:24469635, PubMed:27174676). Regulates expression of KHDRBS2/SLIM-1 in defined neuron populations in the hippocampus by modifying its alternative splicing resulting in a transcript predicted to undergo nonsense-mediated decay (PubMed:25505328). Can bind FABP9 mRNA (PubMed:19916944). May play a role as a negative regulator of cell growth. Inhibits cell proliferation.|||Self-associates to form homooligomers; dimerization increases RNA affinity (By similarity). Interacts with KHDRBS2/SLM-1 (By similarity). Interacts with KHDRBS1/SAM68; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:10077576). Interacts with the splicing regulatory proteins SFRS9, SAFB and YTHDC1. Interacts with HNRPL, RBMX, RBMY1A1, p85 subunit of PI3-kinase, SERPINB5 (By similarity).|||The proline-rich site binds the SH3 domain of the p85 subunit of PI3-kinase. http://togogenome.org/gene/10090:Adamts18 ^@ http://purl.uniprot.org/uniprot/Q4VC17 ^@ Cofactor|||PTM|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||The precursor is cleaved by a furin endopeptidase.|||extracellular matrix http://togogenome.org/gene/10090:Fnip2 ^@ http://purl.uniprot.org/uniprot/D3YUC5|||http://purl.uniprot.org/uniprot/Q80TD3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FNIP family.|||Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:23582324). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (By similarity). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (By similarity). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (By similarity). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (By similarity). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (By similarity). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (By similarity). May play a role in the signal transduction pathway of apoptosis induced by O6-methylguanine-mispaired lesions (PubMed:19137017).|||Cytoplasm|||Homodimer and homomultimer. Heterodimer and heteromultimer with FNIP1. Interacts (via C-terminus) with FLCN (via C-terminus). Phosphorylated FLCN is preferentially bound. Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interacts with PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase. Interacts with HSP70, HSP90AA1, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4.|||Lysosome membrane|||Membrane|||Mice lacking both Fnip1 and Fnip2 show enlarged polycystic kidneys.|||Phosphorylated by AMPK. http://togogenome.org/gene/10090:4930486L24Rik ^@ http://purl.uniprot.org/uniprot/Q80UB0 ^@ Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Expressed in testis and ovary. Low level in spleen, epididymis, kidney, and uterus. Expressed in primary cultures of Sertoli cells.|||Secreted|||This protein is distinct from Tes/Testin which is a LIM domain protein. http://togogenome.org/gene/10090:Sdf2 ^@ http://purl.uniprot.org/uniprot/Q9DCT5 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Secreted|||Ubiquitously expressed with highest expression in liver and kidney. http://togogenome.org/gene/10090:Or4c11c ^@ http://purl.uniprot.org/uniprot/A2ATJ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lck ^@ http://purl.uniprot.org/uniprot/E9Q696|||http://purl.uniprot.org/uniprot/P06240 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on Tyr-394, increasing enzymatic activity, this site is dephosphorylated by PTN22. Phosphorylated on Tyr-505 by CSK, decreasing activity. Dephosphorylated by PTPRC/CD45. Dephosphorylation at Tyr-394 by PTPN2 negatively regulates T-cells differentiation (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Binds to the cytoplasmic domain of cell surface receptors, such as AXL, CD2, CD4, CD5, CD8, CD44, CD45 and CD122. Also binds to effector molecules, such as PI4K, VAV1, RASA1, FYB1 and to other protein kinases including CDK1, RAF1, ZAP70 and SYK. Binds to phosphatidylinositol 3'-kinase (PI3K) from T-lymphocytes through its SH3 domain and to the tyrosine phosphorylated form of KHDRBS1/p70 through its SH2 domain. Interacts with SQSTM1. Interacts with phosphorylated LIME1. Interacts with CBLB and PTPRH. Interacts with RUNX3. Forms a signaling complex with EPHA1, PTK2B and PI3-KINASE; upon activation by EFNA1 which may regulate T-lymphocytes migration. Associates with ZAP70 and RHOH; these interactions allow LCK-mediated RHOH and CD3 subunit phosphorylation in the presence of functional ZAP70. Interacts with CEACAM1 (via cytoplasmic domain); mediates CEACAM1 phosphorylation resulting in PTPN6 recruitment that dephosphorylates TCR stimulation-induced CD247 and ZAP70. Interacts with FYB2 (By similarity). Interacts with CD160. Interacts with CD48.|||Cell membrane|||Levels remain relatively constant throughout T-cell ontogeny.|||Membrane|||Mice show a dramatic reduction in the level of peripheral T-cells, with 5-10% of wild-type levels. T-cells also exhibit a 10-fold decrease in proliferative response.|||Myristoylation is required prior to palmitoylation.|||Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP (By similarity). Interacts with UNC119; this interaction plays a crucial role in activation of LCK (By similarity).|||Palmitoylation regulates association with the plasma membrane and could be mediated by ZDHHC2.|||Present at a low level in most T-cells, and at an elevated level in LSTRA and Thy19 (T-cell lymphoma) cells.|||The SH2 domain mediates interaction with SQSTM1. Interaction is regulated by Ser-59 phosphorylation (By similarity).|||The relative activities of the inhibitory tyrosine-protein kinase CSK and the activating tyrosine-protein phosphatase PTPRC/CD45 determine the level of LCK activity. These interactions allow rapid and efficient activation of LCK in response to TCR stimulation (By similarity).|||cytosol http://togogenome.org/gene/10090:Tlcd3a ^@ http://purl.uniprot.org/uniprot/Q3TVE0|||http://purl.uniprot.org/uniprot/Q5ND56 ^@ Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with GGT7 isoform 3 and SLC3A2.|||Membrane http://togogenome.org/gene/10090:Sp4 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VJR5|||http://purl.uniprot.org/uniprot/K4DI62|||http://purl.uniprot.org/uniprot/Q6DFV2 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rpl34-ps1 ^@ http://purl.uniprot.org/uniprot/Q9D1R9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL34 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||Endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Fastkd2 ^@ http://purl.uniprot.org/uniprot/Q922E6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAST kinase family.|||Mitochondrion matrix|||Monomer. Found in a complex with GRSF1, DDX28, DHX30 and FASTKD5. Associates with the 16S mitochondrial rRNA (16S mt-rRNA). Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA.|||Plays an important role in assembly of the mitochondrial large ribosomal subunit. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation. May play a role in mitochondrial apoptosis.|||Ubiquitously expressed (PubMed:18771761). Expression detected in spleen, testis, colon, heart, smooth muscle, kidney, brain, lung, liver, brown and white adipose tissue with highest expression in testis, heart and smooth muscle.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Hsf2 ^@ http://purl.uniprot.org/uniprot/A0A1W2P8F8|||http://purl.uniprot.org/uniprot/P38533|||http://purl.uniprot.org/uniprot/Q8BWK6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HSF family.|||Cytoplasm|||DNA-binding homotrimer in stressed or heat shocked cells, otherwise found as a homodimer.|||DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. In higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked. HSF2 is expressed in a form that binds DNA constitutively but loses DNA binding by incubation at greater than 41 degrees C.|||In the 7-day-old testis, isoform beta is expressed at significantly higher levels than isoform alpha. As development proceeds, the levels of isoform alpha gradually increase so that it is the predominant isoform in mature testes.|||Isoform alpha is expressed predominantly in testis while isoform beta is expressed predominantly in heart and brain.|||Nucleus http://togogenome.org/gene/10090:Uap1l1 ^@ http://purl.uniprot.org/uniprot/Q3TW96 ^@ Sequence Caution|||Similarity ^@ Belongs to the UDPGP type 1 family.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:Eln ^@ http://purl.uniprot.org/uniprot/P54320 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the elastin family.|||Elastin is formed through the cross-linking of its soluble precursor tropoelastin. Cross-linking is initiated through the action of lysyl oxidase on exposed lysines to form allysine. Subsequent spontaneous condensation reactions with other allysine or unmodified lysine residues result in various bi-, tri-, and tetrafunctional cross-links. The most abundant cross-links in mature elastin fibers are lysinonorleucine, allysine aldol, desmosine, and isodesmosine.|||Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.|||Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle.|||The polymeric elastin chains are cross-linked together into an extensible 3D network. Forms a ternary complex with BGN and MFAP2. Interacts with MFAP2 via divalent cations (calcium > magnesium > manganese) in a dose-dependent and saturating manner. Interacts with FBLN5 and FBN1. Forms a ternary complex with FBN1 and FBLN2 or FBLN5. Interacts with MFAP4 in a Ca (2+)-dependent manner; this interaction promotes ELN self-assembly (By similarity). Interacts with EFEMP2 with moderate affinity (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Ak4 ^@ http://purl.uniprot.org/uniprot/Q3U489|||http://purl.uniprot.org/uniprot/Q9WUR9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adenylate kinase family. AK3 subfamily.|||Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis.|||Expressed in kidney, liver, stomach, brain, spinal cord, heart, ovary, oviduct, colon, jejunum, ileum and testis (at protein level) (PubMed:19492028, PubMed:19130895). In the brain, expressed in the pyramidal cells of the cerebrum and glial cells in the cerebellum (at protein level) (PubMed:19492028). In the heart, expressed by myocytes (at protein level) (PubMed:19492028). In the kidney, expressed in the proximal to distal tubule in the cortex and the outer and inner zones of the medulla (at protein level) (PubMed:19492028). In the stomach, expressed in stratified squamous epithelia in the forestomach and in the gastric pit and mucus producing cells of the glandular stomach (at protein level) (PubMed:19492028). Expressed in epithelial cells of the jejunum, ileum, and colon (at protein level) (PubMed:19492028). In the testis, expressed by spermatocytes (at protein level) (PubMed:19492028). In the ovaries, expressed by oocytes, follicular epithelial cells, and corpus luteum cells (at protein level) (PubMed:19492028). In the oviduct, expressed in the epithelia of the isthmus and the ciliated cells of the ampulla (at protein level) (PubMed:19492028). Expressed in the pyramidal cells in the hippocampus (PubMed:9813319).|||Expressed in the central nervous system in a region-specific manner from the middle stage of embryogenesis to the adulthood in the rodent.|||Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates (By similarity). Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor (By similarity). Also displays broad nucleoside diphosphate kinase activity (By similarity). Plays a role in controlling cellular ATP levels by regulating phosphorylation and activation of the energy sensor protein kinase AMPK (By similarity). Plays a protective role in the cellular response to oxidative stress (By similarity).|||Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Also displays broad nucleoside diphosphate kinase activity.|||Mitochondrion matrix|||Monomer (By similarity). Interacts with SLC25A5/ANT2 (By similarity).|||Monomer. http://togogenome.org/gene/10090:Eno1b ^@ http://purl.uniprot.org/uniprot/P17182|||http://purl.uniprot.org/uniprot/Q5FW97 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the enolase family.|||Binds two Mg(2+) per subunit. Required for catalysis and for stabilizing the dimer.|||Cell membrane|||Cytoplasm|||During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells, and to the alpha/gamma heterodimer in nerve cells. In embryonic muscle, ENO1 is highly expressed until 17 dpc. Decreased levels from P5.|||Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses. May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons. Stimulates immunoglobulin production.|||ISGylated.|||Lysine 2-hydroxyisobutyrylation (Khib) by p300/EP300 activates the phosphopyruvate hydratase activity.|||Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific. ENO1 interacts with PLG in the neuronal plasma membrane and promotes its activation. The C-terminal lysine is required for this binding (By similarity). In vitro, interacts with several glycolytic enzymes including PKM, PGM, CKM and aldolase (PubMed:9169614). Also binds troponin, in vitro (PubMed:9169614). Interacts with ENO4 and PGAM2 (PubMed:23446454). Interacts with CMTM6 (By similarity).|||Testis. Found in the principal piece of sperm tail (at protein level). The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons. In striated muscle, expression of ENO1 appears to be independent of fiber type. http://togogenome.org/gene/10090:Tnfaip8l2 ^@ http://purl.uniprot.org/uniprot/Q9D8Y7 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis. Plays a regulatory role in the Toll-like signaling pathway by determining the strength of LPS-induced signaling and gene expression (PubMed:18455983). Inhibits TCR-mediated T-cell activation and negatively regulate T-cell function to prevent hyperresponsiveness (By similarity). Inhibits also autolysosome formation via negatively modulating MTOR activation by interacting with RAC1 and promoting the disassociation of the RAC1-MTOR complex (PubMed:34524845). Plays an essential role in NK-cell biology by acting as a checkpoint and displaying an expression pattern correlating with NK-cell maturation process and by negatively regulating NK-cell maturation and antitumor immunity (By similarity). Mechanistically, suppresses IL-15-triggered mTOR activity in NK-cells (PubMed:34524845).|||Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.|||By TNF in fibroblasts.|||Cytoplasm|||Expressed in thymus, spleen, lymph node and small intestine, but not in liver, heart, muscle, testis, spinal cord or brain. Up-regulated in the spinal cord of mice with experimental autoimmune encephalomyelitis. Constitutively expressed by macrophages, B and T-lymphocytes at various developmental stages.|||Lysosome|||May interact with CASP8; however, such result is unclear since could not reproduce the interaction with CASP8. Interacts with RAC1.|||Nucleus|||Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers association with BTRC and subsequent ubiquitination and degradation.|||The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding (By similarity).|||Ubiquitinated in a BTRC-depdent manner; leading to degradation mediated through the proteasome pathway.|||When infected with lymphocytic choriomeningitis virus (LCMV), TIPE2-deficient mice exhibit significantly enhanced CD4(+) and CD8(+) T-cell immune responses compared with WT mice (PubMed:18455983). TIPE2-deficient NK-cells exhibit enhanced activation, cytotoxicity, and IFN-gamma production upon stimulation and enhanced response to IL-15 for maturation (PubMed:34524845). http://togogenome.org/gene/10090:Dcps ^@ http://purl.uniprot.org/uniprot/Q9DAR7 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HIT family.|||Cytoplasm|||Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with very poor efficiency. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) to m7GMP. May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCPS to m7GMP. Binds to m7GpppG and strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. Inhibits activation-induced cell death.|||Homodimer. Associates with components of the exosome multienzyme ribonuclease complex, such as EXOSC3 and EXOSC4. Interacts with NDOR1.|||Nucleus|||The C-terminal histidine triad (HIT) motif and the N-terminal domain are required for the decapping activity. The N-terminus is necessary but not sufficient for binding cap structures.|||The hydrolytic product 7-methylguanosine diphosphate (m7GDP) efficiently inhibits the decapping scavenger activity and acts as a competitive inhibitor in vitro. Inhibited by 2,4-diaminoquinazoline. http://togogenome.org/gene/10090:Cdk6 ^@ http://purl.uniprot.org/uniprot/Q0VBK8|||http://purl.uniprot.org/uniprot/Q64261 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast) (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Expressed in subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles whose neural precursor cells (NPC) give rise to dentate granule neurons and olfactory bulb (OB) interneurons, respectively. Expressed in the neuroepithelium of the cerebral cortex of the developing brain.|||Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 (By similarity). Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding (By similarity).|||Nucleus|||Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans (By similarity). May play a role in the centrosome organization during the cell cycle phases.|||Slight anemia and defective proliferation of some hematopoietic cells, thymocytes and progenitor cells. Females are reduced in size and often sterile. Prevents the expansion of neuronally committed precursors by prematurely exiting the cell cycle and lengthening G1 phase duration, reducing concomitantly the production of newborn neurons.|||Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity.|||centrosome|||ruffle http://togogenome.org/gene/10090:Ttll4 ^@ http://purl.uniprot.org/uniprot/Q80UG8 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Arg-722 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Belongs to the tubulin--tyrosine ligase family.|||Cytoplasm|||Highly expressed in testis (PubMed:17499049). Expressed in brain, heart, kidney, liver, lung, muscle and spleen (PubMed:17499049). In the brain, expressed in ependymal cilia, the cortex and the striatum (PubMed:23897886). Expressed in blastomere (PubMed:29593216).|||Knockout mice show hypoglutamylation of KLF4 resulting in KLF4 proteasome-mediated degradation in early-stage embryos and impaired early embryonic development.|||Monoglutamylase which modifies both tubulin and non-tubulin proteins, adding a single glutamate on the gamma-carboxyl group of specific glutamate residues of target proteins (PubMed:17499049, PubMed:21074048, PubMed:20530212, PubMed:26829768). Involved in the side-chain initiation step of the polyglutamylation reaction but not in the elongation step (PubMed:17499049, PubMed:21074048). Preferentially modifies beta-tail tubulin over the alpha-tubulin (PubMed:17499049). Monoglutamylates nucleosome assembly proteins NAP1L1 and NAP1L4 (PubMed:17499049). Monoglutamylates nucleotidyltransferase CGAS, leading to inhibition of CGAS catalytic activity, thereby preventing antiviral defense function (PubMed:26829768). Involved in KLF4 glutamylation which impedes its ubiquitination, thereby leading to somatic cell reprogramming, pluripotency maintenance and embryogenesis (PubMed:29593216).|||The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Psmc3ip ^@ http://purl.uniprot.org/uniprot/C4PFH5|||http://purl.uniprot.org/uniprot/O35047 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HOP2 family.|||Highly expressed in testis and more specifically in spermatocytes. Detected in spleen, ovary and thymus.|||Infertility. Males exhibit testicular hypoplasia with lack of spermatozoa. Spermatocytes arrest at the stage of pachytene-like chromosome condensation and spermatogenesis is blocked at prophase of meiosis I. Axial elements are fully developed, but synapsis is limited. While meiotic double-stranded breaks are formed and processed, they fail to be repaired.|||Interacts with the DNA-binding domain of the nuclear receptors NR3C1/GR, ESR2/ER-beta, THRB and RXRA (By similarity). Forms a stable heterodimer with MND1. Interacts with PSMC3/TBP1.|||Nucleus|||Overexpressed at day 11 in the embryo.|||Phosphorylated by PKA, PKC and MAPK.|||Plays an important role in meiotic recombination. Stimulates DMC1-mediated strand exchange required for pairing homologous chromosomes during meiosis. The complex PSMC3IP/MND1 binds DNA, stimulates the recombinase activity of DMC1 as well as DMC1 D-loop formation from double-strand DNA. This complex stabilizes presynaptic RAD51 and DMC1 filaments formed on single strand DNA to capture double-strand DNA. This complex stimulates both synaptic and presynaptic critical steps in RAD51 and DMC1-promoted homologous pairing. May inhibit HIV-1 viral protein TAT activity and modulate the activity of proteasomes through association with PSMC3. http://togogenome.org/gene/10090:Tmem8b ^@ http://purl.uniprot.org/uniprot/B1AWJ5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM8 family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||May function as a regulator of the EGFR pathway. Probable tumor suppressor which may function in cell growth, proliferation and adhesion (By similarity).|||May interact with EZR.|||Mitochondrion|||N-glycosylated.|||Nucleus http://togogenome.org/gene/10090:Gins1 ^@ http://purl.uniprot.org/uniprot/Q8K1A2|||http://purl.uniprot.org/uniprot/Q9CZ15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GINS1/PSF1 family.|||Chromosome|||Component of the GINS complex which is a heterotetramer of GINS1, GINS2, GINS3 and GINS4. Forms a stable subcomplex with GINS4. GINS complex interacts with DNA primase in vitro. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex.|||Nucleus|||Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. http://togogenome.org/gene/10090:Zfy2 ^@ http://purl.uniprot.org/uniprot/P20662 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family. ZFX/ZFY subfamily.|||Nucleus|||Probable transcriptional activator. Binds to the consensus sequence 5'-AGGCCY-3' (By similarity).|||The binding of ZFY to DNA is mediated by the interaction of the GGCC core base pairs with zinc fingers 12 and 13. http://togogenome.org/gene/10090:Nwd1 ^@ http://purl.uniprot.org/uniprot/A6H603 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ May interact with HSP90AA1, HSP90AB1 and BAG2.|||May play a role in the control of androgen receptor (AR) protein steady-state levels.|||cytosol http://togogenome.org/gene/10090:Gnl1 ^@ http://purl.uniprot.org/uniprot/P36916 ^@ Domain|||Function|||Similarity ^@ Belongs to the TRAFAC class YlqF/YawG GTPase family.|||In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.|||Possible regulatory or functional link with the histocompatibility cluster. http://togogenome.org/gene/10090:Rhox4e ^@ http://purl.uniprot.org/uniprot/Q504P9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Polr3h ^@ http://purl.uniprot.org/uniprot/Q9D2C6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. Interacts with RPC9 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNA. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm21650 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Mzb1 ^@ http://purl.uniprot.org/uniprot/Q9D8I1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a hormone-regulated adipokine/pro-inflammatory cytokine that is implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes. May have a role in the onset of insulin resistance.|||Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion. May exert its effect by acting as a molecular chaperone or as an oxidoreductase as it displays a low level of oxidoreductase activity. Helps to diversify peripheral B-cell functions by regulating Ca(2+) stores, antibody secretion and integrin activation.|||Belongs to the MZB1 family.|||Endoplasmic reticulum|||Endoplasmic reticulum lumen|||Expressed predominantly in the spleen and lymph nodes. Abundantly expressed in marginal zone B and B1 cells. High expression in mesenteric adipose tissue (MAT). Expressed also in pancreas, perigonadal adipose tissue (PAT), uterus, subcutaneous adipose tissue, heart, muscle, ovary and liver. Very low expression is detected in brown adipose tissue. In PAT, significantly higher expression in stromal-vascular cell than in adipocytes. Expressed in macrophage RAW 264.7 cell line. Down-regulated in For-knockout female MAT at 5 months (obese state) followed by steep up-regulation at 9 months (prediabetic condition) when mutants progress towards the metabolic syndrome.|||Forms an interchain disulfide bond with IgM monomers.|||Part of the ER chaperone complex, a multi-protein complex in the endoplasmic reticulum containing a large number of molecular chaperones which associates with unassembled incompletely folded immunoglobulin heavy chains. Interacts with HSP90B1 and PDIA3 in a calcium-dependent manner.|||Secreted|||Up-regulated during plasma cell differentiation. http://togogenome.org/gene/10090:Pou1f1 ^@ http://purl.uniprot.org/uniprot/Q00286 ^@ Disease Annotation|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the POU transcription factor family. Class-1 subfamily.|||Defects in Pou1f1 are the cause of the dwarf (dw) phenotype which interrupts the normal development of the anterior pituitary gland, resulting in the loss of expression of growth hormone, prolactin and thyroid-stimulating hormone, and hypoplasia of their respective cell types.|||Interacts with PITX1. Interacts with LHX3. Interacts with ELK1.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Activates growth hormone and prolactin genes. Specifically binds to the consensus sequence 5'-TAAAT-3'.|||Unable to transactivate. Only about 1/7 as abundant as isoform 1. http://togogenome.org/gene/10090:Ric8b ^@ http://purl.uniprot.org/uniprot/Q80XE1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synembryn family.|||Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP (By similarity). Able to potentiate G(olf)-alpha-dependent cAMP accumulation suggesting that it may be an important component for odorant signal transduction.|||Interacts with GDP-bound G alpha proteins GNAI1, GNAL, GNAS and GNAQ. Does not interact with G-alpha proteins when they are in complex with subunits beta and gamma.|||Predominantly expressed in the mature olfactory sensory neurons and also in a few regions in the brain.|||cell cortex http://togogenome.org/gene/10090:Vmn2r42 ^@ http://purl.uniprot.org/uniprot/D3Z1K8|||http://purl.uniprot.org/uniprot/O35192 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem9b ^@ http://purl.uniprot.org/uniprot/Q9JJR8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM9 family.|||Early endosome membrane|||Enhances production of pro-inflammatory cytokines induced by TNF, IL1B, and TLR ligands. Has a role in TNF activation of both the NF-kappaB and MAPK pathways.|||Lysosome membrane|||N-glycosylated. http://togogenome.org/gene/10090:Or51f1e ^@ http://purl.uniprot.org/uniprot/E9PXW4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Med27 ^@ http://purl.uniprot.org/uniprot/E0CZG8|||http://purl.uniprot.org/uniprot/Q9DB40 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 27 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.|||Nucleus http://togogenome.org/gene/10090:Ggn ^@ http://purl.uniprot.org/uniprot/Q80WJ1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic vesicle|||Isoform 1 and isoform 3 interact with FANCL. Isoform 1 interacts with GGNBP1, ZNF403/GGNBP2 and OAZ3. Isoform 2 interacts with GGNBP1.|||Isoform 2 is detected at high level in adult testis and at lower level in 19-day testis. Not detected in 14-day testis (at protein level). In the developing postnatal gonad, it is not expressed in 6-day-old testes in which the germ cells are almost exclusively spermatogonia or 14-day testis in which the most advanced germ cells are early pachytene spermatocytes. However, it is expressed in 21-day testis tubules containing late pachytene spermatocytes or spermatids. In the postnatal male testis, it is strictly confined to late pachytene spermatocytes through spermatids, a time during which meiosis takes place.|||May be involved in spermatogenesis.|||Testis-specific. Specifically expressed in the germ cells and not in the somatic, Sertoli, or Leydig cells. In adult testis, expression starts in stage VIII pachytene spermatocytes, increases in stage IX and X pachytene spermatocytes, and culminates in stage XI diplotene spermatocytes and the meiotic cells in stage XII. Expression decreases slightly in step 1-3 spermatids, further decreases in step 4-11 spermatids, and is no longer detectable in step 12 spermatids and beyond. Isoform 2 is mainly expressed in testis.|||nucleolus|||perinuclear region http://togogenome.org/gene/10090:Necap1 ^@ http://purl.uniprot.org/uniprot/Q0VB06|||http://purl.uniprot.org/uniprot/Q9CR95 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NECAP family.|||Cell membrane|||Expressed in the brain and spinal cord at 14.5 dpc (at protein level).|||Expressed primarily in brain (at protein level).|||Interacts with AP1G1 and AP2A1 components of the adapter protein complexes AP-1 and AP-2. Interacts with the GAE domain proteins GGA1, GGA2 and GGA3.|||Involved in endocytosis.|||The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself. The WXXF motif 1, which is preceded by an acidic residue and has a glycine in second position mediates specific interaction with AP-1. The WXXF motif 2, which is followed by the C-terminal carboxyl group negative charge, allows specific interaction with AP-2.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Prrt4 ^@ http://purl.uniprot.org/uniprot/B2RU40 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Zfp518a ^@ http://purl.uniprot.org/uniprot/B2RRF6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Through its association with the EHMT1-EHMT2/G9A and PRC2/EED-EZH2 histone methyltransferase complexes may function in gene silencing, regulating repressive post-translational methylation of histone tails at promoters of target genes. http://togogenome.org/gene/10090:Or5al1 ^@ http://purl.uniprot.org/uniprot/Q7TR81 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cybb ^@ http://purl.uniprot.org/uniprot/Q3U6G0|||http://purl.uniprot.org/uniprot/Q61093 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Composed of a heavy chain (beta) and a light chain (alpha). Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts with NCF1. Interacts with calprotectin (S100A8/9) (By similarity). Interacts with NRROS; the interaction is direct and impairs formation of a stable NADPH oxidase complex (PubMed:24739962). Interacts with CYBC1; CYBC1 may act as a chaperone stabilizing Cytochrome b-245 heterodimer (By similarity). Interacts with NCF2; the interaction is enhanced in the presence of GBP7 (PubMed:21551061). The CYBA-CYBB complex interacts with GBP7 (PubMed:21551061).|||Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes.|||Glycosylated.|||Membrane|||Mutants have a very sever defect in controlling bacterial replication.|||Phosphorylated on Ser and Thr residues.|||Undergoes 'Lys-48'-linked polyubiquitination, likely by RNF145, triggering endoplasmic reticulum-associated degradation. http://togogenome.org/gene/10090:Zfp513 ^@ http://purl.uniprot.org/uniprot/Q6PD29 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds DNA. Can associate with the proximal promoter regions of PAX6 and SP4, and their known targets including ARR3, RHO, OPN1MW2 and OPN1SW.|||Nucleus|||Probable cloning artifact.|||Transcriptional regulator that plays a role in retinal development and maintenance.|||Widely expressed. In the eye, expression is greatest in the retina and least in the lens and cornea. http://togogenome.org/gene/10090:Prr15l ^@ http://purl.uniprot.org/uniprot/Q8JZM2 ^@ Similarity ^@ Belongs to the PRR15 family. http://togogenome.org/gene/10090:Cxcl3 ^@ http://purl.uniprot.org/uniprot/Q6W5C0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||By lipopolysaccharide.|||Ligand for CXCR2. Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion.|||Secreted http://togogenome.org/gene/10090:Foxr1 ^@ http://purl.uniprot.org/uniprot/Q3UTB7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in adult germ cells (at protein level) (PubMed:25609838). Expressed in heart, liver, lung and embryonic brain (PubMed:34723967).|||Nucleus|||Reduced survival with the majority of mutants dying during embryonic development and only 23.5% of mutants living to postnatal day 21 (PubMed:34723967). Surviving newborns are smaller and lighter than their wild-type littermates (PubMed:34723967). Newborn brains display decreased cortical thickness and enlarged ventricles (PubMed:34723967).|||Transcription factor which acts as both an activator and a repressor (By similarity). Activates transcription of a number of genes including the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 which are involved in protection against oxidative stress (By similarity). Required for normal brain development (PubMed:34723967).|||Weakly expressed in embryonic gonads.|||perinuclear region http://togogenome.org/gene/10090:Sars ^@ http://purl.uniprot.org/uniprot/P26638|||http://purl.uniprot.org/uniprot/Q8C483 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.|||Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC. Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA.|||Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.|||Cytoplasm|||Homodimer. The tRNA molecule may bind across the dimer. Interacts with SIRT2. Interacts with METTL6; interaction is required for the tRNA N(3)-methylcytidine methyltransferase activity of METTL6.|||Nucleus http://togogenome.org/gene/10090:Fbln5 ^@ http://purl.uniprot.org/uniprot/Q9WVH9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibulin family.|||Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN (By similarity). Stabilizes and organizes elastic fibers in the skin, lung and vasculature. Promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. Vascular ligand for integrin receptors which may play a role in vascular development and remodeling (PubMed:11805835). May act as an adapter that mediates the interaction between FBN1 and ELN (By similarity).|||Homodimer. Monomer, homodimerizes in presence of Ca(2+). Interacts with ELN (By similarity). Interacts (via N-terminus) with the integrins ITGAV/ITGB3, ITGAV/ITGB5 and ITGA9/ITGB1 (PubMed:11805835). Interacts with FBN1 (via N-terminal domain). Forms a ternary complex with ELN and FBN1 (By similarity). Interacts with EFEMP2 with moderate affinity (By similarity).|||Mice survive to adulthood, but have a tortuous aorta with loss of compliance, severe emphisema and loose skin. They exhibit a severely disorganized elastic fiber system throughout the body.|||N-glycosylated.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Best3 ^@ http://purl.uniprot.org/uniprot/Q6H1V1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.|||Cell membrane|||Forms calcium-sensitive chloride channels. Permeable to bicarbonate (By similarity). http://togogenome.org/gene/10090:Prdm12 ^@ http://purl.uniprot.org/uniprot/A2AJ77 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Expression starts around 9.0 dpc in the neural folds, which give rise to neural crest cells. Neural crest cells develop into various tissues, including the sensory ganglia that contain nociceptor cell bodies. Prominently expressed in sensory spinal ganglia (dorsal root ganglia) but not in sympathetic ganglia during the time when sensory neurons emerge (10.5 dpc-13.5 dpc), mature and differentiate (14.5 dpc-postnatal day 14).|||Involved in the positive regulation of histone H3-K9 dimethylation.|||Nucleus http://togogenome.org/gene/10090:Svbp ^@ http://purl.uniprot.org/uniprot/A2A7P9|||http://purl.uniprot.org/uniprot/Q99LQ4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SVBP family.|||Cytoplasm|||Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146868, PubMed:31363758, PubMed:35482892). Also required to enhance the solubility and secretion of VASH1 and VASH2 (By similarity). Plays a role in axon and excitatory synapse formation (PubMed:31235911).|||Highly expressed in bone marrow, spleen and testis.|||Interacts with VASH1 and VASH2.|||Mice display a significant reduction in whole brain volume, with a particular decrease in white matter (PubMed:31363758). Neurons show decreased, but not abolished, tubulin detyrosination, leading to an accumulation of tyrosinated tubulin. This causes delayed axonal differentiation and morphologically disturbed dendritic branching (PubMed:31363758). Mice show behavioral abnormalities, including increased activity and reduced social investigation (PubMed:31363758). Mice lacking both Matcap and Svbp are viable but show a reduction in brain volume: microcephaly is associated with proliferative defects during neurogenesis and abnormal behavior (PubMed:35482892). Cells lacking both Matcap and Svbp show abolished tubulin detyrosination (PubMed:35482892).|||Secreted|||cytoskeleton http://togogenome.org/gene/10090:Tyro3 ^@ http://purl.uniprot.org/uniprot/P55144 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in the brain and lower levels in other tissues.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.|||Cell membrane|||Monomer and homodimer. Interacts (via N-terminus) with extracellular ligands TULP1 and GAS6. Interacts with PIK3R1; this interaction increases PI3-kinase activity (By similarity).|||Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.|||knockout mice are fertile, but male animals that lack all three receptors TYRO3, AXL and MERTK produce no mature sperm. http://togogenome.org/gene/10090:1700067K01Rik ^@ http://purl.uniprot.org/uniprot/Q8CF25 ^@ Similarity ^@ Belongs to the UPF0575 family. http://togogenome.org/gene/10090:Golga3 ^@ http://purl.uniprot.org/uniprot/P55937 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cleaved by caspases in apoptotic cells.|||Cytoplasm|||Extended rod-like protein with coiled-coil domains.|||Golgi stack membrane|||Highly expressed in testis. Transcripts can be found in spermatids during spermatogenesis. No expression in Leydig cells, spermatogonia or spermatocytes. Detected at low levels in all tissues.|||Homodimer. Interacts with GOLGA7. Interacts with GOPC (By similarity).|||Plays an important role in spermatogenesis and/or testis development. Probably identical with the serologically detectable male antigen (SDM). Probably involved in maintaining Golgi structure. http://togogenome.org/gene/10090:Rnase6 ^@ http://purl.uniprot.org/uniprot/Q3V3L3|||http://purl.uniprot.org/uniprot/Q9D244 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pancreatic ribonuclease family.|||Cytoplasmic granule|||Highly expressed in spleen (at protein level) (PubMed:15693621, PubMed:25075772). Has little or no expression in healthy kidneys (at protein level) (PubMed:25075772). Detected at high levels in infected kidneys (at protein level) (PubMed:25075772). Expressed at low levels in bladder (PubMed:15693621, PubMed:25075772). Also detected in skeletal muscle, heart and bone marrow (PubMed:15693621).|||Interacts (via N-terminus) with bacterial lipopolysaccharide (LPS).|||Lysosome|||Ribonuclease which shows a preference for the pyrimidines uridine and cytosine (PubMed:15693621). Has potent antibacterial activity against a range of Gram-positive and Gram-negative bacteria, including P.aeruginosa, A.baumanii, M.luteus, S.aureus, E.faecalis, E.faecium, S.saprophyticus and E.coli (PubMed:15693621, PubMed:25075772). Causes loss of bacterial membrane integrity, and also promotes agglutination of Gram-negative bacteria (By similarity). Probably contributes to urinary tract sterility (PubMed:25075772). Bactericidal activity is independent of RNase activity (By similarity).|||Secreted|||Up-regulated in bone marrow derived macrophages in response to the uropathogenic E.coli strain CFT073. http://togogenome.org/gene/10090:Cbr1 ^@ http://purl.uniprot.org/uniprot/B2RXY7|||http://purl.uniprot.org/uniprot/P48758 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Cytoplasm|||Embryonic lethal.|||Monomer.|||NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol (By similarity). Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione. In addition, participates in the glucocorticoid metabolism by catalyzing the NADPH-dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue (PubMed:28878267, PubMed:33785425). http://togogenome.org/gene/10090:Cttnbp2 ^@ http://purl.uniprot.org/uniprot/B9EJA2 ^@ Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Due to intron retention.|||Erroneous CDS prediction and frameshift.|||Interacts with CTTN/cortactin SH3 domain. Interacts with STRN, STRN4/zinedin and MOB4/phocein; this interaction may regulate dendritic spine distribution of STRN and STRN4 in hippocampal neurons (By similarity). Activation of glutamate receptors weakens the interaction with STRN and STRN4 (By similarity).|||Isoform 2 is predominantly expressed in brain (at protein level). In the brain, expressed at high levels in hypothalamus and striatum and at lower levels in cerebellum and cortex.|||May be due to competing acceptor splice site.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance.|||cell cortex|||dendritic spine http://togogenome.org/gene/10090:Eva1a ^@ http://purl.uniprot.org/uniprot/Q91WM6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a regulator of programmed cell death, mediating both autophagy and apoptosis.|||Belongs to the EVA1 family.|||Endoplasmic reticulum membrane|||Lysosome membrane http://togogenome.org/gene/10090:Bfsp1 ^@ http://purl.uniprot.org/uniprot/A2AMT1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Ala-35 following proteolytic cleavage at Leu-34.|||Belongs to the intermediate filament family.|||Cell membrane|||Complete loss of beaded filament structures in lens epithelial cells.|||Cytoplasm|||Detected in eye lens fiber cells (at protein level) (PubMed:14985306, PubMed:19029034, PubMed:21745462). Expressed in retinal lens epithelial cells (at protein level) (PubMed:27559293).|||First expressed in retinal lens fiber cells during elongation and differentiation, becoming localized to the cytoplasm as fiber cells mature and the beaded filament network forms at 3 weeks of age.|||Myristoylated at Gly-432 following proteolytic cleavage at Asp-431.|||Part of a complex required for lens intermediate filament formation composed of BFSP1, BFSP2 and CRYAA (By similarity). Identified in a complex that contains VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (PubMed:21745462). Found in a complex composed of PPL (via C-terminal linker domain), BFSP1 and BFSP2 in the retinal lens (PubMed:19029034). Within the complex interacts with BFSP2 (PubMed:19029034). Interacts (via C-terminus) with MIP (via C-terminus) in aged lens fiber cells (By similarity).|||Proteolytically cleaved during lens cell fiber differentiation with increased fragmentation as fiber cell age increases.|||Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA (PubMed:27559293). Involved in altering the calcium regulation of MIP water permeability (By similarity).|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Clcn5 ^@ http://purl.uniprot.org/uniprot/Q3UL16|||http://purl.uniprot.org/uniprot/Q8C6W8|||http://purl.uniprot.org/uniprot/Q9WVD4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family. ClC-5/CLCN5 subfamily.|||Cell membrane|||Endosome membrane|||Golgi apparatus membrane|||Interacts with NEDD4 and NEDD4L.|||Kidney specific.|||Membrane|||Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable).|||Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation. http://togogenome.org/gene/10090:Rbm46 ^@ http://purl.uniprot.org/uniprot/P86049|||http://purl.uniprot.org/uniprot/S4R1Y9 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Essential for male and female fertility, playing a crucial role in regulating germ cell development by ensuring the proper progression of meiosis prophase I (PubMed:36129965, PubMed:36001654, PubMed:36726756). Regulates mitotic-to-meiotic transition in spermatogenesis by forming a complex with MEIOC and YTHDC2 which recognizes and down-regulates mitotic transcripts for a successful meiotic entry (PubMed:36129965). Required for normal synaptonemal complex formation during meiosis, binding meiotic cohesin subunit mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions and positively regulating their translation (PubMed:36726756). Required for spermatogonial differentiation in both developing and adult testis (PubMed:36129965).|||Expressed in the testis and ovary (at protein level) (PubMed:36129965, PubMed:36001654, PubMed:36726756). Expressed in spermatogonia and spermatocytes in testis (at protein level) (PubMed:36129965, PubMed:36001654).|||Interacts with YTHDC2, MEIOC, MOV10, CNOT6L, DDX4, UPF1 and PABPC1.|||Male and female mice are infertile and show meiotic arrest in spermatocytes and oocytes (PubMed:36129965, PubMed:36001654, PubMed:36726756). Severely impaired spermatogenesis with a complete absence of postmeiotic germ cells and a marked decrease of spermatocytes in meiotic prophase I seen in adult testis (PubMed:36001654). Spermatogonial differentiation is impaired in developing testis (PubMed:36129965). RBM46-target cohesin subunits display unaltered mRNA levels but have reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest (PubMed:36726756). http://togogenome.org/gene/10090:Or1d2 ^@ http://purl.uniprot.org/uniprot/Q7TRW7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdhgc5 ^@ http://purl.uniprot.org/uniprot/Q91XW9 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Fbxw15 ^@ http://purl.uniprot.org/uniprot/L7N1X6 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected at 18 dpc, and then decreases thereafter to a very low level at the day of birth. Detected again at 48 hours postpartum, and then increases at 96 hours until 6 days after birth.|||Endoplasmic reticulum|||Nucleus|||Part of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Interacts with KAT7 and SKP1.|||Specifically expressed in oocytes from follicles of the medullary region of the ovary.|||Substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes KAT7 ubiquitination and subsequent degradation in collaboration with MAP2K1 kinase, leading to reduced histone H3K14 acetylation and increased cell proliferation.|||Up-regulated in response to bacterial lipopolysaccharides (LPS).|||cytosol http://togogenome.org/gene/10090:Zfp408 ^@ http://purl.uniprot.org/uniprot/H7BX78 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sult1e1 ^@ http://purl.uniprot.org/uniprot/Q9D566 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Syne1 ^@ http://purl.uniprot.org/uniprot/A0A1L1STC6|||http://purl.uniprot.org/uniprot/Q0VGB8|||http://purl.uniprot.org/uniprot/Q6PI72|||http://purl.uniprot.org/uniprot/Q6ZWR6|||http://purl.uniprot.org/uniprot/Q7TQH5 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nesprin family.|||Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. The SUN2:SYNE1/KASH1 LINC complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE1/KASH1 peptides bind at the interface of adjacent SUN domains. Self-associates. Interacts with SYNE3. Interacts with SUN3; proposed to form a spermatogenesis-specific LINC complex with SUN3 during sperm head formation. May interact with MUSK. Interacts with SPAG4/SUN4. Interacts with EMD and LMNA in vitro. Interacts with F-actin via its N-terminal domain. Interacts with DCTN1 and DYNC1I1/2; suggesting the association with the dynein-dynactin motor complex. Interacts (via KASH domain) with TMEM258 (By similarity).|||Expressed in C2F3 and CH310T1/2 cells, brain and skeletal muscle (at protein level).|||Incomplete sequence.|||Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 seem to act redundantly in cerebellum, midbrain, brain stem, and other brain regions except cerebral cortex and hippocampus. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.|||Nucleus|||Nucleus envelope|||Nucleus outer membrane|||The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.|||The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.|||cytoskeleton|||sarcomere http://togogenome.org/gene/10090:Serf1 ^@ http://purl.uniprot.org/uniprot/O88892 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SERF family.|||Expressed in brain (at protein level) (PubMed:31034892). Highly expressed in the testis (PubMed:9731538).|||Interacts with SNCA; this interaction promotes the aggregation of SNCA.|||Nucleus|||Positive regulator of amyloid protein aggregation and proteotoxicity (By similarity). Induces conformational changes in amyloid proteins, such as APP, HTT, and SNCA, driving them into compact formations preceding the formation of aggregates (By similarity).|||cytosol http://togogenome.org/gene/10090:Kcnj9 ^@ http://purl.uniprot.org/uniprot/P48543|||http://purl.uniprot.org/uniprot/Q544N3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with GIRK1 to form a G-protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger. When alone, fail to give functional channels in Xenopus oocytes. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ9 subfamily.|||Expressed mainly in the brain, some expression in the skeletal muscle.|||Membrane|||The PDZ-binding motif specifically binds the PDZ domain of SNX27: the specificity for SNX27 is provided by the 2 residues located upstream (Glu-388 and Ser-389) of the PDZ-binding motif.|||This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. http://togogenome.org/gene/10090:Fndc3b ^@ http://purl.uniprot.org/uniprot/Q6NWW9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FNDC3 family.|||May be positive regulator of adipogenesis.|||Membrane http://togogenome.org/gene/10090:Or2w6 ^@ http://purl.uniprot.org/uniprot/Q8VFH0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Orai1 ^@ http://purl.uniprot.org/uniprot/A3KCG1|||http://purl.uniprot.org/uniprot/Q8BWG9 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to a report, ORAI1 has been shown to colocalize with UBQLN1 in the autophagosome as a target for autophagic degradation; ORAI1 is however not an autophagosomal protein.|||Basolateral cell membrane|||Belongs to the Orai family.|||Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1. CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT (By similarity). Plays a prominent role in Ca(2+) influx at the basolateral membrane of mammary epithelial cells independently of the Ca(2+) content of endoplasmic reticulum or Golgi stores. May mediate transepithelial transport of large quantities of Ca(2+) for milk secretion (PubMed:23840669) (By similarity).|||Cell membrane|||Cys-197 is oxidated, leading to inactivation of channel activity.|||Expressed in lactating mammary epithelium (at protein level).|||Interacts with STIM1 and STIM2; this regulates channel activity. Interacts with CALM; this may displace STIM1 and STIM2 and might thereby modulate channel activity. Interacts with CRACR2A/EFCAB4B; the interaction is direct and takes place in absence of Ca(2+). Forms a complex with CRACR2A/EFCAB4B and STIM1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations. Interacts with SLC35G1. Interacts with UBQLN1. Interacts with ADCY8; interaction is calcium store depletion independent; interaction occurs in membrane raft; interaction increases markedly after store depletion; positively regulates SOCE-induced adenylate cyclase activity; contributes to the targeting of ADCY8 to discrete regions of the plasma membrane that are shielded from other calcium events (By similarity). Interacts with EFHB; the interaction takes place upon Ca(2+)-store depletion (By similarity). Interacts (via N- and C-termini) with ATP2C2 (via N-terminus); this interaction regulates Ca(2+) influx at the plasma membrane. Interacts with TSPAN18; this interaction regulates ORAI1 exit from the endoplasmic (ER), and/or Golgi, and trafficking to the cell surface (By similarity).|||Membrane|||N-glycosylated. N-glycosylation inhibits channel activity.|||Oxidation at Cys-197 leads to inactivation of channel activity.|||Ubiquitinated. http://togogenome.org/gene/10090:Zfp574 ^@ http://purl.uniprot.org/uniprot/Q8BY46 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Fmo9 ^@ http://purl.uniprot.org/uniprot/Q14DT3|||http://purl.uniprot.org/uniprot/Q8C116 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Akap1 ^@ http://purl.uniprot.org/uniprot/O08715 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A (PubMed:9065479, PubMed:9182549). Anchors them to the cytoplasmic face of the mitochondrial outer membrane or allows them to reside in the endoplasmic reticulum (PubMed:9065479, PubMed:9182549). Involved in mitochondrial-mediated antiviral innate immunity (By similarity). Promotes translocation of NDUFS1 into mitochondria to regulate mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) activity (PubMed:32072193). Under diabetic conditions, myocardial AKAP1 expression decreases which blocks the translocation of NDUFS1 from the cytosol to mitochondria (PubMed:32072193). Reduction of NDUFS1 in mitochondria decreases ATP production and increases mitochondrial ROS level, which causes mitochondrial dysfunction and cell apoptosis, respectively, thereby leading to cardiac dysfunction (PubMed:32072193).|||Endoplasmic reticulum|||Highest expression in testis, heart, liver, skeletal muscle, intestine and kidney, followed by brain and lung. No expression in spleen. Isoform 1/D-AKAP1A is expressed predominantly in testis whereas isoform 4/D-AKAP1D is expressed primarily in liver (PubMed:9065479). Expression is decreased in hearts of diabetic mice (at protein level) (PubMed:32072193).|||Interacts with SLC8A3 (PubMed:24101730). Interacts with CFAP91. Interacts with CLPB (By similarity). Interacts with NDUFS1 (PubMed:32072193).|||Knockout in diabetogenic agent streptozotocin-treated mice results in significant cardiac dysfunction which is accompanied by impaired mitochondrial function and increased cardiomyocyte apoptosis.|||Mitochondrion|||Mitochondrion outer membrane|||RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer. http://togogenome.org/gene/10090:Spin2d ^@ http://purl.uniprot.org/uniprot/B1B0R2 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or6x1 ^@ http://purl.uniprot.org/uniprot/Q8VFN6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp326 ^@ http://purl.uniprot.org/uniprot/A0A0R4J098|||http://purl.uniprot.org/uniprot/O88291 ^@ Developmental Stage|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AKAP95 family.|||Component of the DBIRD complex. Interacts with CCAR2; the interaction is direct (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions (By similarity). May also play a role in neuronal differentiation. Able to bind DNA and activate expression in vitro.|||Nucleus matrix|||Ubiquitously expressed in adult tissues. Highly expressed in neuronal tissues such as brain and neural tube.|||Upon retinoic acid treatment.|||Weakly expressed during 9.5 dpc and 10.5 dpc, expressed at highest level in 11.5 dpc and gradually decreases thereafter. During the cell cycle, it is weakly expressed in G0 and G1 phases. It increases during G1, S, G2 and M phases. http://togogenome.org/gene/10090:Crlf3 ^@ http://purl.uniprot.org/uniprot/Q9Z2L7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytokine receptor-like factor 3 family.|||Cytoplasm|||May play a role in the negative regulation of cell cycle progression. http://togogenome.org/gene/10090:Henmt1 ^@ http://purl.uniprot.org/uniprot/Q8CAE2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily. HEN1 family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Methyltransferase that adds a 2'-O-methyl group at the 3'-end of piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. This probably protects the 3'-end of piRNAs from uridylation activity and subsequent degradation. Stabilization of piRNAs is essential for gametogenesis.|||Specifically expressed in testis. http://togogenome.org/gene/10090:Rnf138 ^@ http://purl.uniprot.org/uniprot/Q9CQE0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated.|||Chromosome|||E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination. Recruited to sites of double-strand breaks following DNA damage and specifically promotes double-strand break repair via homologous recombination. Two different, non-exclusive, mechanisms have been proposed. According to a report, regulates the choice of double-strand break repair by favoring homologous recombination over non-homologous end joining (NHEJ): acts by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku complex from DNA breaks, thereby promoting homologous recombination. According to another report, cooperates with UBE2Ds E2 ubiquitin ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous recombination by mediating ubiquitination of RBBP8/CtIP. Together with NLK, involved in the ubiquitination and degradation of TCF/LEF. Also exhibits auto-ubiquitination activity in combination with UBE2K. May act as a negative regulator in the Wnt/beta-catenin-mediated signaling pathway.|||Interacts with NLK. Interacts with XRCC5/Ku80. Interacts with RBBP8/CtIP.|||The zinc finger domains (C2H2-type and C2HC-type zinc fingers) bind DNA and mediate recruitment to double-strand break sites. They show strong preference for DNA with 5'- or 3'-single-stranded overhangs, while they do not bind blunt-ended double-stranded DNA or poly(ADP-ribose) (PAR) polymers. http://togogenome.org/gene/10090:Rps16 ^@ http://purl.uniprot.org/uniprot/A4FUS1|||http://purl.uniprot.org/uniprot/P14131|||http://purl.uniprot.org/uniprot/Q5CZY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS9 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Cluap1 ^@ http://purl.uniprot.org/uniprot/Q8R3P7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CLUAP1 family.|||E9.5 embryos are still viable but die thereafter. Mutant embryos are runted, have exhibit enlarged pericardial sacs, and defects in neural tube development. There is a complete absence of cilia in E9.5 embryos. Sonic hedgehog (SHH) signaling is severely disrupted with down-regulation of PTCH1 and GLI1.|||Expressed in all tissues tested including heart, kidney, skeletal muscle, eye, liver, ovary, oviduct, testes, lung and brain. Elevated levels in multiciliated cells such as the bronchioles of the lungs, ependymal cells of the brain and cells with a single primary cilia of heart and kidney.|||Interacts with CLU/clusterin. Interacts with UBXN10; the interaction is direct.|||Nucleus|||Required for cilia biogenesis. Appears to function within the multiple intraflagellar transport complex B (IFT-B). Key regulator of hedgehog signaling.|||cilium http://togogenome.org/gene/10090:Esyt2 ^@ http://purl.uniprot.org/uniprot/Q3TZZ7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic.|||Belongs to the extended synaptotagmin family.|||Cell membrane|||Endoplasmic reticulum membrane|||Homodimer. Interacts with ESYT1 and ESYT3. Interacts with FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2 complex; identified in a complex with the AP-2 complex and FGFR1 (By similarity).|||Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex (By similarity). Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (By similarity).|||The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium. The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (By similarity).|||The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (By similarity). http://togogenome.org/gene/10090:Tgm4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J071|||http://purl.uniprot.org/uniprot/Q8BZH1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated with the mammalian reproductive process. Plays an important role in the formation of the seminal coagulum through the cross-linking of specific proteins present in the seminal plasma. Transglutaminase is also required to stabilize the copulatory plug.|||Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 1 Ca(2+) ion per subunit.|||Expressed in the coagulating gland and in the dorsal part of the prostate. Not expressed in the brain, heart, kidney, liver, lung, muscle, pancreas, spleen, stomach, testis and thymus.|||Homodimer.|||Secreted http://togogenome.org/gene/10090:Hhex ^@ http://purl.uniprot.org/uniprot/P43120 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expressed during hematopoiesis.|||Interacts with CD81; the interaction prevents nuclear translocation of HHEX (PubMed:23665349). Interacts (via N-terminus) with SOX13; abolishes the SOX13-mediated inhibition of WNT-mediated transcriptional activity via competitive inhibition of the SOX13-TCF7 complex (PubMed:20028982). Interacts with EIF4E; the interaction inhibits EIF4E-mediated mRNA nuclear export (PubMed:12554669).|||Nucleus|||Recognizes the DNA sequence 5'-ATTAA-3' (PubMed:10804173). Transcriptional repressor (PubMed:10804173). Activator of WNT-mediated transcription in conjunction with CTNNB1 (PubMed:16936074). Establishes anterior identity at two levels; acts early to enhance canonical WNT-signaling by repressing expression of TLE4, and acts later to inhibit NODAL-signaling by directly targeting NODAL (PubMed:16936074). Inhibits EIF4E-mediated mRNA nuclear export (By similarity). May play a role in hematopoietic differentiation (PubMed:8096636).|||nuclear body http://togogenome.org/gene/10090:Ifitm6 ^@ http://purl.uniprot.org/uniprot/Q3SXF0 ^@ Similarity ^@ Belongs to the CD225/Dispanin family. http://togogenome.org/gene/10090:Rps9 ^@ http://purl.uniprot.org/uniprot/Q6ZWN5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS4 family.|||Component of the small ribosomal subunit (PubMed:36517592). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Hace1 ^@ http://purl.uniprot.org/uniprot/Q3U0D9 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases. Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion. Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division. Specifically interacts with GTP-bound RAC1, mediating ubiquitination and subsequent degradation of active RAC1, thereby playing a role in host defense against pathogens (By similarity). May also act as a transcription regulator via its interaction with RARB.|||Endoplasmic reticulum|||Golgi stack membrane|||Interacts with RAB1 (RAB1A, RAB1B or RAB1C), RAB4 (RAB4A or RAB4B) and RAB11 (RAB11A or RAB11B); in a GTP-dependent manner. Interacts with RAC1; in a GTP-dependent manner. Interacts with the 26S proteasomal complex through the 20S core proteasomal subunit (By similarity). Interacts with RARB.|||Mice develop spontaneous, late-onset cancer. Moreover, tumor incidence in mice heterozygous for a p53/Tp53 mutation in higher in a Hace1-deficient background. http://togogenome.org/gene/10090:Atg14 ^@ http://purl.uniprot.org/uniprot/Q8CDJ3 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATG14 family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Expression is controlled by forkhead box O FoxO1 transcription factor and circadian rhythms.|||Forms homooligomers; homo-oligomerization is essential for the roles in membrane tethering and enhancement of SNARE-mediated fusion (By similarity). Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex I (PI3KC3-C1) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with ATG14 (PubMed:19270693, PubMed:22745922, PubMed:23332761). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (By similarity). PI3KC3-C1 can associate with further regulatory subunits (PubMed:24849286). Interacts with PIK3CB (PubMed:21059846). Interacts (via coiled-coil domain) with BECN2 (via coiled-coil domain); this interaction is tighter than BECN2 self-association (By similarity). Interacts with the STX17-SNAP29 binary t-SNARE complex (By similarity). Interacts with NRBF2 (PubMed:24849286) Interacts with PIK3C3 and BECN1; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with STEEP1; the interaction is required for trafficking of STING1 from the endoplasmic reticulum (By similarity).|||Preautophagosomal structure membrane|||Required for both basal and inducible autophagy (PubMed:19270696, PubMed:19270693). Determines the localization of the autophagy-specific PI3-kinase complex PI3KC3-C1 (By similarity). Plays a role in autophagosome formation and MAP1LC3/LC3 conjugation to phosphatidylethanolamine (PubMed:19270696, PubMed:19270693). Promotes BECN1 translocation from the trans-Golgi network to autophagosomes (By similarity). Enhances PIK3C3 activity in a BECN1-dependent manner. Essential for the autophagy-dependent phosphorylation of BECN1 (By similarity). Stimulates the phosphorylation of BECN1, but suppresses the phosphorylation of PIK3C3 by AMPK (PubMed:23332761). Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion (By similarity). Modulates the hepatic lipid metabolism (PubMed:22992773).|||The N-terminal cysteine repeats are required for proper localization to the endoplasmic reticulum.|||The coiled-coil domain is required for BECN1- and PIK3C3-binding and for autophagy.|||The final 80 residues in the C-terminus define a minimum required region for autophagosome binding called BATS.|||Widely expressed.|||autophagosome membrane http://togogenome.org/gene/10090:Sdf2l1 ^@ http://purl.uniprot.org/uniprot/Q9ESP1 ^@ Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By tunicamycin and a calcium ionophore, A23187.|||Endoplasmic reticulum lumen|||Ubiquitously expressed with high expression in the testis, ovary, uterus, and low expression in heart and skeletal muscle. http://togogenome.org/gene/10090:Rnf170 ^@ http://purl.uniprot.org/uniprot/Q8CBG9 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Constitutively associated with the ERLIN1/ERLIN 2 complex. Interacts with activated ITPR1.|||E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway. Also involved in ITPR1 turnover in resting cells.|||Endoplasmic reticulum membrane|||It is uncertain whether Met-1 or Met-30 is the initiator. Initiation at Met-30 is supported by sequence similarity with mammalian orthologs and by a Kozak context more favorable compared to that at Met-1. http://togogenome.org/gene/10090:Best1 ^@ http://purl.uniprot.org/uniprot/O88870 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.|||Cell membrane|||Forms calcium-sensitive chloride channels. Permeable to bicarbonate (By similarity).|||Phosphorylated by PP2A.|||Tetramer or pentamers. May interact with PPP2CB and PPP2R1B (By similarity). http://togogenome.org/gene/10090:Topors ^@ http://purl.uniprot.org/uniprot/Q80Z37 ^@ Function|||Induction|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ By genotoxic agents such as cisplatin and camptothecin.|||Contaminating sequence. Potential poly-A sequence.|||Functions as an E3 ubiquitin-protein ligase and as a E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates p53/TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA-damage-induced cell death through IKBKE sumoylation.|||Interacts with TOP1. Interacts with the SUMO1 conjugating enzyme UBE2I. Interacts with SUMO1. Interacts with NKX3-1; polyubiquitinates NKX3-1 and induces its proteasomal degradation. Interacts with SIN3A; sumoylates SIN3A. Interacts with IKBKE; induced by DNA damage (By similarity). Interacts with p53/TP53. Interacts with PARK7/DJ-1.|||Nucleus|||PML body|||Phosphorylation at Ser-99 regulates the E3 ubiquitin-protein ligase activity but not the SUMO1-protein ligase activity. Phosphorylation at Ser-718 increases the E3 ubiquitin-protein ligase activity versus the E3 SUMO1-protein ligase activity resulting in increased p53/TP53 ubiquitination and degradation.|||Sumoylated. http://togogenome.org/gene/10090:Fam13c ^@ http://purl.uniprot.org/uniprot/G3X9S1|||http://purl.uniprot.org/uniprot/Q5DTU9|||http://purl.uniprot.org/uniprot/Q6NXX8|||http://purl.uniprot.org/uniprot/Q8BLV7|||http://purl.uniprot.org/uniprot/Q9DBR2 ^@ Similarity ^@ Belongs to the FAM13 family. http://togogenome.org/gene/10090:Ube2n ^@ http://purl.uniprot.org/uniprot/A2RTT4|||http://purl.uniprot.org/uniprot/P61089 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (By similarity). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (PubMed:22424771, PubMed:28039360, PubMed:28123943, PubMed:29499132).|||Belongs to the ubiquitin-conjugating enzyme family.|||Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.|||Cytoplasm|||Heterodimer with UBE2V2 (By similarity). Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity (By similarity). Interacts with RNF8 and RNF168 (By similarity). Interacts with RNF11 (By similarity). Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys-63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair (By similarity). Interacts with ARIH2 (via RING-type 2) (By similarity). Interacts with OTUB1; leading to inhibit E2-conjugating activity (By similarity). Interacts with GPS2; leading to inhibit E2-conjugating activity (PubMed:22424771). Interacts with RIGI and RNF135; involved in RIGI ubiquitination and activation (By similarity).|||Nucleus|||The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains (PubMed:22424771, PubMed:28039360). This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UB2V1, catalyzes the RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:22424771). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway. http://togogenome.org/gene/10090:Atp6v1b1 ^@ http://purl.uniprot.org/uniprot/Q91YH6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the ATPase alpha/beta chains family.|||Highly expressed in the kidney; found in early distal nephron, encompassing thick ascending limbs and distal convoluted tubules and in the alpha-intercalated cells of the cortical collecting ducts (at protein level) (PubMed:14585495, PubMed:29993276). Expressed in the olfactory epithelium (at protein level) (PubMed:23028982). Expressed at lower levels in the testis (PubMed:14585495).|||Mice show a higher urinary pH and a more severe metabolic acidosis after oral acid challenge in comparison to wild-type littermates (PubMed:16174750). Mice show diminished innate avoidance behavior (revealed as a decrease in freezing time and an increase in the number of sniffs in the presence of trimethyl-thiazoline) and diminished innate appetitive behavior (a decrease in time spent investigating the urine of the opposite sex) (PubMed:23028982).|||Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:16174750, PubMed:23028982). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Essential for the proper assembly and activity of V-ATPase (By similarity). In renal intercalated cells, mediates secretion of protons (H+) into the urine thereby ensuring correct urinary acidification (PubMed:16174750). Required for optimal olfactory function by mediating the acidification of the nasal olfactory epithelium (PubMed:23028982).|||The PDZ-binding motif mediates interactions with NHERF1 and SCL4A7.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Forms a complex with NHERF1 and SCL4A7 (By similarity). http://togogenome.org/gene/10090:Ptprr ^@ http://purl.uniprot.org/uniprot/Q62132 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 7 subfamily.|||Cell membrane|||Cytoplasm|||Expressed in the heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Isoform alpha is expressed throughout the granular layer of the cerebellar but not within the Purkinje cells, also in the villi of the ileum and jejunum and both the villi and crypts of the duodenum. Isoform beta is expressed only in the Purkinje cells. Isoform gamma is expressed throughout the brain, the villi and crypts of the duodenum, jejunum and ileum and expressed at low levels in the proximal colon.|||Interacts with MAPKs.|||Isoform gamma is the only family member developmentally expressed. Expressed throughout the brain in 15.5 day embryos and in cranial nerve cells, skeletal tissues such as neural crest-derived face bones, and the periphery of cartilaginous skeletal elements including the rib and vertebrae anlage. On day 17.5, expression was observed throughout the brain, trigeminal ganglion, cranofacial bones, oral-facial structures, cervical vertebrae, axis and the ileum. Expression continued in the vertebral column throughout ossification.|||Sequesters mitogen-activated protein kinases (MAPKs) such as MAPK1, MAPK3 and MAPK14 in the cytoplasm in an inactive form. The MAPKs bind to a dephosphorylated kinase interacting motif, phosphorylation of which by the protein kinase A complex releases the MAPKs for activation and translocation into the nucleus. Isoform gamma may have a role in patterning and cellular proliferation of skeletal elements in the precartilaginous/cartilaginous skeleton. http://togogenome.org/gene/10090:Sez6 ^@ http://purl.uniprot.org/uniprot/Q7TSK2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 11.5 dpc, expression is localized to the preplate and is absent from the ventricular zone which is the most prominent layer during early cortical development. At 13 dpc highly expressed in postmitotic, maturing neurons of the developing cortical plate and subplate. At 15 dpc expression is closely tied with the emergence of the neocortical layers and hippocampus. In the cortex, expression diminishes after birth, but continues in the deep layer pyramidal neurons and neuronal subpopulations of layer II/III. In the hippocampus, expression persists in CA1 pyramidal neurons and in the dentate gyrus. Postnatally, expression remains high in specific cortical neuron populations, particularly those of the deep cortical layers.|||Belongs to the SEZ6 family.|||Brain-specific. Expressed in extrasynaptic and synaptic subcellular fractions (at protein level). Expression correlates with the most active periods of cortical neurogenesis and neuronal maturation. Expression is restricted to the gray matter with higher levels in the forebrain including the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, striatum, hippocampal CA1 pyramidal cell layer and cerebral cortex. Expression is up-regulated with the convulsant drug, pentylenetetrazole.|||Cell membrane|||Cytoplasm|||Glycosylated.|||May play a role in cell-cell recognition and in neuronal membrane signaling. Seems to be important for the achievement of the necessary balance between dendrite elongation and branching during the elaboration of a complex dendritic arbor. Involved in the development of appropriate excitatory synaptic connectivity.|||Mice show reduced exploratory behavior and motor coordination, altered maze performance, and poorer memory retention. Molecular, morphological, and electrophysiological evidence of defects in dendritic arbor patterning was also seen. Secreted and membrane-bound isoforms in null mutants exerted opposite actions. The secreted isoform showed an increased neurite number, while, the membrane-bound isoform displayed a decrease in dendritic arborization. Embryos were viable, fertile and normal in other respects. Mice lacking Sez6, Sez6l1, Sez6l2 exhibited motor discordination, and Purkinje cells were often innervated by multiple climbing fibers with different neuronal origins in the cerebellum.|||Secreted|||Synapse|||dendrite http://togogenome.org/gene/10090:Gcsam ^@ http://purl.uniprot.org/uniprot/Q6RFH4 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||GCSAM transgenic mice develop B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis strating from 12 months of age.|||Highly expressed in normal germinal center (GC) B-cells. Expressed in spleen and, to a lesser extent, bone marrow.|||Interacts with ACTB and MYH2; the interaction with MYH2 is increased by IL6-induced phosphorylation. Interacts (via C-terminus) with ARHGEF11 (via DH domain). Interacts with ARHGEF12. Interacts with SYK; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity.|||Involved in the negative regulation of lymphocyte motility. It mediates the migration-inhibitory effects of IL6. Serves as a positive regulator of the RhoA signaling pathway. Enhancement of RhoA activation results in inhibition of lymphocyte and lymphoma cell motility by activation of its downstream effector ROCK. Is a regulator of B-cell receptor signaling, that acts through SYK kinase activation.|||Phosphorylation on tyrosine residues can be induced by IL6. Phosphorylation is mediated by LYN.|||Targeted by the ubiquitin E3 ligase subunit FBXO10 to mediate its ubiquitination and degradation. http://togogenome.org/gene/10090:Scgb1b3 ^@ http://purl.uniprot.org/uniprot/J3QJY4 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Hpse ^@ http://purl.uniprot.org/uniprot/Q6YGZ1 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 79 family.|||Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.|||Expressed in skin, mainly in the stratum granulosum and the first layer of the stratum corneum in the upper part of the epidermis. Also detected in hair follicles and in sebaceous glands.|||Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity. Interacts with TF; the interaction, inhibited by heparin, enhances the generation of activated factor X and activates coagulation. Interacts with HRG; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts with SDC1; the interaction enhances the shedding of SDC1 (By similarity). Interacts with HPSE2 (By similarity).|||In 18.5 day embryos, expressed in the peri-chondrium, periosteum and at the chondro-osseus junction of developing bone.|||Inhibited by EDTA and activated by calcium and magnesium (By similarity). Inhibited by laminarin sulfate and, to a lower extent, by heparin and sulfamin.|||Lysosome membrane|||N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility.|||Nucleus|||Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and the 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme (By similarity).|||Secreted http://togogenome.org/gene/10090:Vmp1 ^@ http://purl.uniprot.org/uniprot/Q99KU0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VMP1 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Interacts with BECN1 (By similarity). Interacts with TJP1. Interacts with TP53INP2. Interacts with TMEM41B. Interacts with ATP2A2, PLN and SLN; competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2. Interacts with ATG2A (By similarity).|||Mutants show early embryonic lethality with lipid accumulation in the visceral endoderm (PubMed:31526472). Intestinal epithelial cell-specific knockout show accumulation of lipids in intestinal epithelial cells (PubMed:31526472).|||Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes (By similarity). Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine (By similarity). Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by ATG2 (ATG2A or ATG2B) to mediate autophagosome assembly (PubMed:17940279, PubMed:28890335). Regulates ATP2A2 activity to control ER-isolation membrane contacts for autophagosome formation (By similarity). In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required (By similarity). Modulates ER contacts with lipid droplets, mitochondria and endosomes (By similarity). Plays an essential role in formation of cell junctions (PubMed:31526472). Upon stress such as bacterial and viral infection, promotes formation of cytoplasmic vacuoles followed by cell death (By similarity). Involved in the cytoplasmic vacuolization of acinar cells during the early stage of acute pancreatitis (By similarity).|||The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain.|||Vacuole membrane http://togogenome.org/gene/10090:Lpar4 ^@ http://purl.uniprot.org/uniprot/Q8BLG2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Transduces a signal by increasing the intracellular calcium ions and by stimulating adenylyl cyclase activity. The rank order of potency for agonists of this receptor is 1-oleoyl- > 1-stearoyl- > 1-palmitoyl- > 1-myristoyl- > 1-alkyl- > 1-alkenyl-LPA (By similarity). http://togogenome.org/gene/10090:Depdc1a ^@ http://purl.uniprot.org/uniprot/Q8CIG0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Can form dimers. Interacts with ZNF224 (By similarity).|||May be involved in transcriptional regulation as a transcriptional corepressor. The DEPDC1A-ZNF224 complex may play a critical role in bladder carcinogenesis by repressing the transcription of the A20 gene, leading to transport of NF-KB protein into the nucleus, resulting in suppression of apoptosis of bladder cancer cells (By similarity).|||Nucleus http://togogenome.org/gene/10090:Copa ^@ http://purl.uniprot.org/uniprot/Q8BTF0|||http://purl.uniprot.org/uniprot/Q8CIE6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ COPI-coated vesicle membrane|||Cytoplasm|||Golgi apparatus membrane|||Membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits. Probably interacts with PEX11A. Interacts with SCYL1. Interacts with JAGN1 (By similarity). Interacts with TMEM41B (By similarity).|||Secreted|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity).|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors.|||Xenin stimulates exocrine pancreatic secretion. It inhibits pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic secretion and to affect small and large intestinal motility. In the gut, xenin interacts with the neurotensin receptor (By similarity). http://togogenome.org/gene/10090:Trappc3 ^@ http://purl.uniprot.org/uniprot/O55013|||http://purl.uniprot.org/uniprot/Q3U9K9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAPP small subunits family. BET3 subfamily.|||Endoplasmic reticulum|||Homodimer.|||Homodimer. Component of the multisubunit transport protein particle (TRAPP) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12. Heterodimer with TRAPPC6A. The heterodimer TRAPPC3-TRAPPC6A interacts with TRAPPC2L. Heterodimer with TRAPPC6b. The heterodimer TRAPPC6B-TRAPPC3 interacts with TRAPPC1 likely providing a core for TRAPP complex formation.|||May play a role in vesicular transport from endoplasmic reticulum to Golgi.|||Widely expressed. Expressed in lung, heart, liver, spleen, brain and kidney.|||cis-Golgi network http://togogenome.org/gene/10090:Cyp2d26 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZY2|||http://purl.uniprot.org/uniprot/Q8CIM7 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Spns1 ^@ http://purl.uniprot.org/uniprot/Q8R0G7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.|||Expressed in liver (at mRNA and protein levels).|||Interacts with BCL2 and BCL2L1.|||Lysosome membrane|||Plays a critical role in the phospholipid salvage pathway from lysosomes to the cytosol (PubMed:36161949). Mediates the rate-limiting, proton-dependent, lysosomal efflux of lysophospholipids, which can then be reacylated by acyltransferases in the endoplasmic reticulum to form phospholipids (PubMed:36161949). Selective for zwitterionic headgroups such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), can also transport lysophosphatidylglycerol (LPG), but not other anionic lysophospholipids, sphingosine, nor sphingomyelin (PubMed:36161949). Transports lysophospholipids with saturated, monounsaturated, and polyunsaturated fatty acids, such as 1-hexadecanoyl-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine and 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, respectively (PubMed:36161949). Can also transport lysoplasmalogen (LPC with a fatty alcohol) such as 1-(1Z-hexadecenyl)-sn-glycero-3-phosphocholine. Essential player in lysosomal homeostasis (PubMed:36161949). Crucial for cell survival under conditions of nutrient limitation. May be involved in necrotic or autophagic cell death (By similarity). http://togogenome.org/gene/10090:Scgb1b27 ^@ http://purl.uniprot.org/uniprot/Q91WB5 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Dnah5 ^@ http://purl.uniprot.org/uniprot/Q8VHE6 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein heavy chain family.|||Defects in Dnah5 are the cause of primary ciliary dyskinesia (PCD). PCD is characterized by recurrent respiratory infections, situs inversus and ciliary immotility and hydrocephalus.|||Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.|||Embryos show a weak expression confined to the node from 7.0 to 8.25 dpc.|||Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required for structural and functional integrity of the cilia of ependymal cells lining the brain ventricles.|||Interacts with DNAL1 (By similarity). Consists of at least two heavy chains and a number of intermediate and light chains.|||Mice display defects in motility of the ependymal cells lining the brain ventricles and aqueduct. This results in impaired flow of cerebrospinal fluid through the cerebral aqueduct and gives rise to closure of the aqueduct and subsequent formation of triventricular hydrocephalus during early postnatal brain development.|||Strongly expressed in lung and kidney and weaker expression seen in brain, heart and testis. In the brain, expressed in ependymal cells lining the brain ventricles and the aqueduct.|||cilium axoneme http://togogenome.org/gene/10090:2310034C09Rik ^@ http://purl.uniprot.org/uniprot/Q9D746 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Disp1 ^@ http://purl.uniprot.org/uniprot/Q3TDN0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dispatched family.|||Death at or soon after 9.5 dpc probably due to abnormal embryonic turning and looping of the heart. Embryos also display defects in development of the forebrain and branchial arches.|||Expression overlaps with the one of SHH and IHH being restricted to tissues that require Hh signaling. PubMed:12372301, reported a more ubiquitous expression which is detected throughout the embryo at 7.5 dpc and is maintained during embryonic development.|||Functions in hedgehog (Hh) signaling. Regulates the release and extracellular accumulation of cholesterol-modified hedgehog proteins and is hence required for effective production of the Hh signal. Synergizes with SCUBE2 to cause an increase in SHH secretion (PubMed:22902404).|||Interacts with SHH; via the cholesterol anchor of the dually lipid-modified SHH (ShhNp) (PubMed:22902404).|||Membrane http://togogenome.org/gene/10090:Scfd2 ^@ http://purl.uniprot.org/uniprot/Q3UXF7|||http://purl.uniprot.org/uniprot/Q8BTY8 ^@ Function|||Similarity ^@ Belongs to the STXBP/unc-18/SEC1 family.|||May be involved in protein transport. http://togogenome.org/gene/10090:Defb13 ^@ http://purl.uniprot.org/uniprot/Q8R2I4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Expressed in testis and to a lesser extent in epididymis (caput, corpus and cauda). Also weakly expressed in kidneys.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Zfp423 ^@ http://purl.uniprot.org/uniprot/Q80TS5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Chimeric cDNA.|||During embryogenesis, it is highly expressed at the dorsal neuroepithelium flanking the roof plate.|||Homodimer (By similarity). Interacts with SMAD1 and SMAD4. Interacts with EBF1 (By similarity). Interacts with PARP1. Interacts with CEP290 (By similarity).|||Mice are runted and ataxic, the cerebellum is underdeveloped, and the vermis is severely reduced, resulting in diminished proliferation by granule cell precursors in the external germinal layer, especially near the midline, and abnormal differentiation and migration of ventricular zone-derived neurons and Bergmann glia. In the remaining cerebellar structures, the Purkinje cells are poorly developed and mislocalized.|||Nucleus|||Transcription factor that can both act as an activator or a repressor depending on the context. Plays a central role in BMP signaling and olfactory neurogenesis. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved in terminal olfactory receptor neurons differentiation; this interaction preventing EBF1 to bind DNA and activate olfactory-specific genes. Involved in olfactory neurogenesis by participating in a developmental switch that regulates the transition from differentiation to maturation in olfactory receptor neurons. Controls proliferation and differentiation of neural precursors in cerebellar vermis formation.|||Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and Olf signaling pathways. C2H2-type zinc fingers 14-19 mediate the interaction with SMAD1 and SMAD4, while zinc fingers 28-30 mediate the interaction with EBF1. zinc fingers 2-8 bind the 5'-CCGCCC-3' DNA sequence in concert with EBF1, while zinc fingers 9-13 bind BMP target gene promoters in concert with SMADs (By similarity).|||Within the cerebellum, Zfp423 is expressed in both ventricular and external germinal zones. Transiently expressed in newly differentiating olfactory-receptor neurons.|||Znf423 gene is a frequent target of retroviral integration in murine B-cell lymphomas. http://togogenome.org/gene/10090:Ssb ^@ http://purl.uniprot.org/uniprot/P32067 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation.|||Interacts with DDX15. May interact with RUFY1 (By similarity).|||Nucleus|||Phosphorylated. http://togogenome.org/gene/10090:Themis ^@ http://purl.uniprot.org/uniprot/Q8BGW0 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the themis family.|||Cytoplasm|||Down-regulated by stimulation through the alpha-beta TCR.|||Expressed in the thymus and to a lesser extent in the spleen but not detectable in non-lymphoid tissues. Highly expressed in thymocytes between the pre-T-cell antigen receptor (pre-TCR) and positive-selection checkpoints and expressed at low level in mature T-cells (at protein level).|||Interacts with PLCG1, ITK, GRB2, and LAT.|||Mice are viable, are born at the expected Mendelian frequency and present no gross abnormalities. They however display a blockade in late T-cell development with defects in thymocyte selection. The number of transitional CD4(+)CD8(int) thymocytes as well as CD4(+) or CD8(+) single-positive thymocytes is lower. Thymocytes show defective positive selection, resulting in fewer mature thymocytes. Negative selection is also impaired. A greater percentage of T-cells have CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes compared to wild-type T-cells.|||Nucleus|||Phosphorylated on Tyr residues quickly after TCR stimulation.|||Plays a central role in late thymocyte development by controlling both positive and negative T-cell selection. Required to sustain and/or integrate signals required for proper lineage commitment and maturation of T-cells. Regulates T-cell development through T-cell antigen receptor (TCR) signaling and in particular through the regulation of calcium influx and phosphorylation of Erk. http://togogenome.org/gene/10090:Alx4 ^@ http://purl.uniprot.org/uniprot/O35137 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||Binds DNA.|||Defects in Alx4 are the cause of Strong luxoid (lst) phenotype. At heterozygosity lst is characterized by preaxial abnormalities of the hindfeet and, very rarely, of the forefeet. Homozygotes show preaxial polydactyly of all four limbs, reductions and duplications of the radius, absence of the tibia, craniofacial defects, reduction of the pubis, and dorsal alopecia.|||Expressed from 8.25 dpc and confined to mesenchymal cells throughout the embryo development. Expression is seen at several sites including craniofacial region, first branchial arch and anterior aspect of the limb bud.|||Expressed in osteoblasts. Not expressed in brain, heart, intestine, kidney, liver, muscle, spleen and testis.|||Nucleus|||Transcription factor involved in skull and limb development. http://togogenome.org/gene/10090:Cdh1 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZW5|||http://purl.uniprot.org/uniprot/P09803 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Does not function as a receptor for L.monocytogenes internalin A (InlA); mutating a single surface-exposed residue confers receptor activity to this protein and promotes uptake of the bacteria.|||Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells (PubMed:11976333). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7 (By similarity).|||Cadherins are calcium-dependent cell adhesion proteins.|||Cell membrane|||During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 (By similarity). Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm (By similarity). The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway (By similarity). Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system (By similarity). The gamma-secretase-mediated cleavage promotes disassembly of adherens junctions (By similarity). During development of the cochlear organ of Corti, cleavage by ADAM10 at adherens junctions promotes pillar cell separation (PubMed:30639848).|||E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production (By similarity).|||Endosome|||Expressed in inner and outer pillar cells of the organ of Corti (at protein level) (PubMed:30639848). Non-neural epithelial tissues.|||Homodimer; disulfide-linked (By similarity). Component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and potentially alpha-catenin/CTNNA1; the complex is located to adherens junctions (PubMed:7982500, PubMed:19759396). Interacts with the TRPV4 and CTNNB1 complex (PubMed:20413591, PubMed:11348595). Interacts with CTNND1 (By similarity). The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex (PubMed:16325582). Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1 (PubMed:18093941). Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs) (By similarity). Interacts with AJAP1 and DLGAP5 (By similarity). Interacts with TBC1D2 (By similarity). Interacts with LIMA1 (By similarity). Interacts with CAV1 (By similarity). Interacts with PIP5K1C (By similarity). Interacts with RAB8B (By similarity). Interacts with DDR1; this stabilizes CDH1 at the cell surface and inhibits its internalization (By similarity). Interacts with RAPGEF2 (By similarity). Interacts with KLRG1 (By similarity). Forms a ternary complex composed of ADAM10, CADH1 and EPHA4; within the complex, CADH1 is cleaved by ADAM10 which disrupts adherens junctions (PubMed:30639848). Interacts with SPEF1 (By similarity). Interacts with CTNNB1 and PKP2 (By similarity).|||In the testis, expression is highest in fetal gonad, then decreases 5-fold in newborn. Detectable in 7-day-old but not in 21-day-old or adult.|||Membrane|||N-glycosylation at Asn-639 is essential for expression, folding and trafficking. Addition of bisecting N-acetylglucosamine by MGAT3 modulates its cell membrane location (By similarity).|||O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4. Ser-287 and Thr-511 are O-manosylated by TMTC2 or TMTC4 but not TMTC1 or TMTC3.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, requires prior phosphorylation at Tyr-756 (By similarity).|||adherens junction|||trans-Golgi network http://togogenome.org/gene/10090:Capn10 ^@ http://purl.uniprot.org/uniprot/Q9ESK3 ^@ Function|||Similarity ^@ Belongs to the peptidase C2 family.|||Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. May play a role in insulin-stimulated glucose uptake (By similarity). http://togogenome.org/gene/10090:Maml1 ^@ http://purl.uniprot.org/uniprot/Q6T264 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions.|||At E9.5, strongly expressed in the telencephalon, first branchial arch, forelimb buds and somites. By 10.5 dpc, continuously expressed in brain and spinal cord. Also expressed in first and second branchial arches and limb buds. By 11.5 dpc, expression in CNS is weak but increases in mesodermal tissues. At 14.5 dpc, detected in epithelial cells in trachea, esophagus and proximal and distal tubules of the developing lungs.|||Belongs to the mastermind family.|||Interacts (via N-terminus) with NOTCH1, NOTCH2, NOTCH3 and NOTCH4 (via ankyrin repeat region). Interacts (via N-terminus) with p53 (via DNA-binding region). Forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1. Also binds CREBBP/CBP and CDK8. Forms a complex with PRAG1, NOTCH1 and MAML1, in a MAML1-dependent manner (PubMed:25038227).|||Nucleus speckle|||The C-terminal region is required for transcriptional activation. http://togogenome.org/gene/10090:Ttc21b ^@ http://purl.uniprot.org/uniprot/E9PVK4|||http://purl.uniprot.org/uniprot/Q0HA38 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 10.5 dpc, widely expressed with more intense expression in the maxillary prominence, branchial arches, limb buds, somites and spinal cord.|||Belongs to the TTC21 family.|||Component of the IFT complex A (IFT-A) complex. IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts directy with WDR35 and TTC21B (By similarity). Interacts with TTC25 (PubMed:25860617).|||Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs). Essential for retrograde trafficking of IFT-1, IFT-B and GPCRs (By similarity). Negatively modulates the SHH signal transduction (PubMed:18327258).|||Probable cloning artifact. Aberrant splice sites.|||cilium axoneme http://togogenome.org/gene/10090:Asap3 ^@ http://purl.uniprot.org/uniprot/Q5U464 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Promotes cell proliferation. http://togogenome.org/gene/10090:Tango2 ^@ http://purl.uniprot.org/uniprot/P54797 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Tango2 family.|||Cytoplasm|||Expressed in fetal liver, lung, heart and kidney (PubMed:8268909). In brain, detected in the olfactory bulb, neocortex and cerebellum (PubMed:18775783). Elevated in mitral cells and minimally expressed in bulb interneurons (PubMed:18775783). In the cortex, restricted to the upper portion of layer 5 (PubMed:18775783). In the cerebellum, excluded from Purkinje cells but expressed in granule cells (PubMed:18775783).|||Golgi apparatus|||Levels increase during embryonic development, drop at postnatal day 0 and increase again during postnatal development, reaching a mmaxium at postnatal day 21 before dropping slightly at postnatal day 60 (PubMed:18775783). In 13 dpc embryos, expressed at high levels in the trachea, liver, esophagus, lung and velo-pharyngeal region (PubMed:8268909). Also detected in the central nervous system (PubMed:8268909).|||May be involved in lipid homeostasis.|||Mitochondrion|||Previous published data showed conflicting results on the intracellular location of TANGO2. Has been reported to be located in the Golgi apparatus (By similarity). However, another study was unable to detect Golgi localization (By similarity). Has been reported to be located in the mitochondrion by several recent studies in mouse and human (PubMed:18775783). However, no mitochondrial localization was detected in another study which reported that the protein is primarily cytoplasmic (By similarity). http://togogenome.org/gene/10090:Dhrs7 ^@ http://purl.uniprot.org/uniprot/Q9CXR1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||DHRS7 was originally reported to be anchored in the endoplasmic reticulum membrane and facing the lumen (By similarity). However, the catalytic moiety was later shown to be facing the cytosol (By similarity).|||Endoplasmic reticulum membrane|||NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including steroids, retinoids and xenobiotics. Catalyzes the reduction/inactivation of 5alpha-dihydrotestosterone to 3alpha-androstanediol, with a possible role in the modulation of androgen receptor function. Involved in the reduction of all-trans-retinal to all-trans-retinol. Converts cortisone to 20beta-dihydrocortisone in vitro, although the physiological relevance of this activity is questionable. Reduces exogenous compounds such as quinones (1,2-naphtoquinone, 9,10-phenantrenequinone and benzoquinone) and other xenobiotics (alpha-diketones) in vitro, suggesting a role in the biotransformation of xenobiotics with carbonyl group. A dehydrogenase activity has not been detected so far. May play a role as tumor suppressor. http://togogenome.org/gene/10090:Capn9 ^@ http://purl.uniprot.org/uniprot/Q9D805 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C2 family.|||Calcium-regulated non-lysosomal thiol-protease.|||Cytoplasm|||Predominantly expressed in stomach and small intestine, although low levels of expression in other organs. http://togogenome.org/gene/10090:Tnfaip8l3 ^@ http://purl.uniprot.org/uniprot/Q3TBL6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a lipid transfer protein. Preferentially captures and shuttles two lipid second messengers, i.e., phosphatidylinositol 4,5- bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and increases their levels in the plasma membrane. Additionally, may also function as a lipid-presenting protein to enhance the activity of the PI3K-AKT and MEK-ERK pathways. May act as a regulator of tumorigenesis through its activation of phospholipid signaling.|||Belongs to the TNFAIP8 family.|||Cell membrane|||Cytoplasm|||Deficient mice develop normally during the first 3 months of life under pathogen-free conditions. However, following subcutaneous injection of the carcinogen 3-methylcholanthrene, deficient mice exhibit markedly delayed skin tumor onset and reduced tumor size compared with wild-type mice.|||The N-terminal domain (AA 2-20) is essential for its effect on cell growth and survival.|||Widely expressed (at protein level). http://togogenome.org/gene/10090:Ap3b1 ^@ http://purl.uniprot.org/uniprot/Q3UPG0|||http://purl.uniprot.org/uniprot/Q9Z1T1 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (PubMed:21998198). AP-3 associates with the BLOC-1 complex (PubMed:21998198). Interacts with KIF3A; interaction is direct; interaction is impaired by pyrophosphorylation of AP3B1 (By similarity).|||Belongs to the adaptor complexes large subunit family.|||Defects in Ap3b1 are the cause of the autosomal recessive phenotype 'pearl' (pe). Pearl mice exhibit hypopigmentation, lysosomal secretion abnormalities, and platelet-dense granules with reduced levels of adenine nucleotides and serotonin. The changes in platelets lead to prolonged bleeding. Additionally, pearl mice exhibit reduced sensitivity in the dark-adapted state (PubMed:9931340).|||Golgi apparatus|||Phosphorylated on serine residues.|||Pyrophosphorylated by 5-diphosphoinositol pentakisphosphate (5-IP7) (PubMed:17873058). Pyrophosphorylation impairs interaction with KIF3A (By similarity). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue (PubMed:17873058).|||Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.|||Ubiquitously expressed.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Faim ^@ http://purl.uniprot.org/uniprot/Q9WUD8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAIM1 family.|||Cytoplasm|||Plays a role as an inducible effector molecule that mediates Fas resistance produced by surface Ig engagement in B cells.|||Widely expressed, with the highest levels in brain, thymus, kidney, and spleen. http://togogenome.org/gene/10090:Cdh13 ^@ http://purl.uniprot.org/uniprot/Q9WTR5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ By contrast to classical cadherins, homodimerization in trans is not mediated by cadherin EC1 domain strand-swapping, but instead through a homophilic adhesive interface which joins two elongated EC1-EC2 domains through a region near their Ca2+-binding sites to form a tetrahedral, X-like shape.|||Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. May act as a negative regulator of neural cell growth.|||Cell membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Tk2 ^@ http://purl.uniprot.org/uniprot/Q8BN51 ^@ Similarity ^@ Belongs to the DCK/DGK family. http://togogenome.org/gene/10090:Or2d36 ^@ http://purl.uniprot.org/uniprot/Q9EPG6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Clcf1 ^@ http://purl.uniprot.org/uniprot/Q3TM06|||http://purl.uniprot.org/uniprot/Q9QZM3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-6 superfamily.|||Forms a heteromeric complex with cardiotrophin-like cytokine CRLF1/CLF-1; the CRLF1-CLCF1 complex is a ligand for the ciliary neurotrophic factor receptor/CNTFR. The CRLF1-CLCF1 heterodimer binds SORL1 (via N-terminal ectodomain); within this complex, the interaction is mediated predominantly by the CRLF1 moiety. The tripartite signaling complex formed by CRLF1, CLCF1 and CNTFR also binds SORL1.|||In complex with CRLF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development (By similarity). Also stimulates B-cells. Binds to and activates the ILST/gp130 receptor (PubMed:10500198).|||Secreted http://togogenome.org/gene/10090:Slc35a1 ^@ http://purl.uniprot.org/uniprot/Q61420 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.|||Golgi apparatus membrane|||Monomer.|||Transports CMP-sialic acid from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges CMP-sialic acid for CMP (PubMed:8755516, PubMed:10085119, PubMed:30985278, PubMed:34015330). Binds both CMP-sialic acid and free CMP, but has higher affinity for free CMP (PubMed:30985278). Also able to exchange CMP-sialic acid for AMP and UMP (By similarity). Also mediates the transport of CDP-ribitol (PubMed:34015330) (By similarity).|||Ubiquitous. Found in all the tissues examined including skeletal muscle, brain, heart, liver, kidney and spleen. http://togogenome.org/gene/10090:Ano5 ^@ http://purl.uniprot.org/uniprot/Q75UR0 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Does not exhibit calcium-activated chloride channel (CaCC) activity.|||Endoplasmic reticulum membrane|||Highly expressed in skeletal muscle, bone tissues and thyroid gland.|||In the developing embryo, expressed mainly in differentiating and developing somites and is associated with myotomal somite lineages.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.|||Up-regulated during the course of myogenic differentiation. Down-regulated during osteoblastic differentiation. http://togogenome.org/gene/10090:Entpd3 ^@ http://purl.uniprot.org/uniprot/Q8BFW6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GDA1/CD39 NTPase family.|||Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates (PubMed:15130768). Has a threefold preference for the hydrolysis of ATP and UTP over ADP and UDP (PubMed:15130768).|||Cell membrane http://togogenome.org/gene/10090:Gab1 ^@ http://purl.uniprot.org/uniprot/A0A1B0GS41|||http://purl.uniprot.org/uniprot/Q505A4|||http://purl.uniprot.org/uniprot/Q9QYY0 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a role in intracellular signaling cascades triggered by activated receptor-type kinases. Plays a role in FGFR1 signaling. Probably involved in signaling by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Involved in the MET/HGF-signaling pathway.|||Belongs to the GAB family.|||Expressed in the inner ear (at protein level) (PubMed:29408807). Expression is detected in the cochlear duct, spiral limbus region, efferent and afferent nerves, and in spiral ganglion neurons (at protein level) (PubMed:29408807).|||Identified in a complex containing FRS2, GRB2, GAB1, PIK3R1 and SOS1 (PubMed:11353842). Forms a tripartite complex containing GAB1, METTL13 and SPRY2 (By similarity). Within the complex interacts with METTL13 (By similarity). Interacts with GRB2 and with other SH2-containing proteins (PubMed:11353842). Interacts with phosphorylated LAT2 (By similarity). Interacts with PTPRJ (By similarity). Interacts (phosphorylated) with PTPN11 (By similarity). Interacts with HCK (By similarity).|||Phosphorylated on tyrosine residue(s) by the epidermal growth factor receptor (EGFR) and the insulin receptor (INSR). Tyrosine phosphorylation of GAB1 mediates interaction with several proteins that contain SH2 domains. Phosphorylated on tyrosine residues by HCK upon IL6 signaling (By similarity). Phosphorylated in response to FGFR1 activation. http://togogenome.org/gene/10090:Pla2g4f ^@ http://purl.uniprot.org/uniprot/Q50L41 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Has calcium-dependent phospholipase and lysophospholipase activities with a potential role in membrane lipid remodeling and biosynthesis of lipid mediators (PubMed:17293613, PubMed:15866882). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:17293613, PubMed:15866882). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis (PubMed:15866882, PubMed:17293613). In myocardial mitochondria, plays a major role in arachidonate release that is metabolically channeled to the formation of cardioprotective eicosanoids, epoxyeicosatrienoates (EETs) (By similarity).|||Mitochondrion|||Stimulated by cytosolic Ca(2+).|||Strongly expressed in thyroid, expressed at intermediate level in stomach and at very low level in large intestine and prostate.|||The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity).|||cytosol http://togogenome.org/gene/10090:Dpp9 ^@ http://purl.uniprot.org/uniprot/Q8BVG4 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S9B family. DPPIV subfamily.|||Detected in hypoglossal cord and first branchial arch at 10.75 dpc (at protein level).|||Detected in kidney, skin, brain, thymus and liver (at protein level).|||Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2 (PubMed:24223149). Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29396289). Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (By similarity). The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP9, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity).|||Homodimer. Forms a ternary complex with NLRP1, composed of a DPP9 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus). Forms a ternary complex with CARD8, composed of a DPP9 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus). In the ternary complex, only one subunit of the DPP9 homodimer is bound to NLRP1 or CARD8.|||Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29396289). Val-boroPro inhibits activity by binding to the active site, mimicking a substrate-bound state, thereby displacing the C-terminal fragment of NLRP1, leading to activation of the NLRP1 inflammasome. In contrast, Val-boroPro does not directly displaces CARD8: it acts by promoting degradation of the N-terminal part of CARD8, leading to indirect disruption of the ternary complex (By similarity).|||cytosol http://togogenome.org/gene/10090:Rcn3 ^@ http://purl.uniprot.org/uniprot/Q8BH97 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CREC family.|||Degraded by PCSK6 and other endoproteases including FURIN and PCSK5.|||During lung development the expression is detected from 15.5 dpc to P1 with a maximum at 17.5 dpc which corresponds to the stage of development of alveolar saccules.|||Endoplasmic reticulum lumen|||Highly expressed in lung and heart. Also detected in liver, spleen, kidney, skeletal muscle, intestine, stomach, and brain.|||Homozygous knockout mice show neonatal lethality (PubMed:26252542). Normally delivered newborn mice exhibit normal gross morphology, early motor activity, and response to painful stimuli (PubMed:26252542). They quickly develop severe respiratory distress with gasping and cyanosis, and die within 20 to 60 minutes after birth (PubMed:26252542). Normally developed trachea and diaphragm structure as well as no obvious gross morphological or histological abnormalities in the heart, brain, or liver suggest that abnormal lung development is the primary cause for the neonatal lethality (PubMed:26252542). Mutant mice exhibit morphological abnormalities of the lungs, including atelectasis with collapse of the alveolar space and unexpanded intra-alveolar septae (PubMed:26252542). This is associated with an impaired maturation of type 2 alveolar epithelial cells which is probably due to their failure to properly produce pulmonary surfactant (PubMed:26252542).|||Interacts with PCSK6 (immature form including the propeptide); probably involved in the maturation and the secretion of PCSK6.|||N-glycosylated.|||Probable molecular chaperone assisting protein biosynthesis and transport in the endoplasmic reticulum (PubMed:26252542). Required for the proper biosynthesis and transport of pulmonary surfactant-associated protein A/SP-A, pulmonary surfactant-associated protein D/SP-D and the lipid transporter ABCA3 (PubMed:26252542). By regulating both the proper expression and the degradation through the endoplasmic reticulum-associated protein degradation pathway of these proteins plays a crucial role in pulmonary surfactant homeostasis (PubMed:26252542). Has an anti-fibrotic activity by negatively regulating the secretion of type I and type III collagens (By similarity). This calcium-binding protein also transiently associates with immature PCSK6 and regulates its secretion (By similarity). http://togogenome.org/gene/10090:Or2a12 ^@ http://purl.uniprot.org/uniprot/Q8VEV0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chrnb4 ^@ http://purl.uniprot.org/uniprot/Q3USV2|||http://purl.uniprot.org/uniprot/Q8R493 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-4/CHRNB4 sub-subfamily.|||Cell membrane|||Membrane|||Neuronal AChR is composed of two different types of subunits: alpha and beta. Beta-4 subunit can be combined to alpha-2, alpha-3 or alpha-4 to give rise to functional receptors. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6. The pentamer alpha3-beta-4 interacts with the conotoxin BuIA. The heteropentamer composed of alpha-3 and beta-4 subunits interacts with the alpha-conotoxin ImI (By similarity).|||Postsynaptic cell membrane|||Predominantly expressed by immature T-cells in the thymus.|||Synaptic cell membrane http://togogenome.org/gene/10090:Serpinb6a ^@ http://purl.uniprot.org/uniprot/F8WIV2|||http://purl.uniprot.org/uniprot/Q4FJQ6|||http://purl.uniprot.org/uniprot/Q60854 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 13.5 dpc, weakly detected in utricle sensory epithelium but not in hair cells. At 16.5 dpc, more prominently detected in crista hair cells. Hair cell expression is sustained in postnatal mice. In cochlea, detected in cochlear hair cells in embryo and in hair cells and the greater epithelial ridge (GER) region in early postnatal age.|||Belongs to the serpin family.|||Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Expressed in the inner ear hair cells, keratinocytes of hair follicles and epidermis in abdominal skin.|||Forms a complex with the monomeric form of beta-tryptase.|||Inhibitor of cathepsin G, kallikrein-8 and thrombin. May play an important role in the inner ear in the protection against leakage of lysosomal content during stress. May be involved in the regulation of serine proteinases present in the brain or extravasated from the blood. http://togogenome.org/gene/10090:Mapk7 ^@ http://purl.uniprot.org/uniprot/Q5NCN8|||http://purl.uniprot.org/uniprot/Q9WVS8 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by tyrosine and threonine phosphorylation. Activated in response to hyperosmolarity, hydrogen peroxide, and epidermal growth factor (EGF) (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Cytoplasm|||Detected in testis, brain, kidney, lung and heart. Detected in total embryo (at protein level).|||Dually phosphorylated on Thr-219 and Tyr-221, which activates the enzyme.|||Interacts with MAP2K5 (By similarity). Forms oligomers. Interacts with MEF2A, MEF2C and MEF2D; the interaction phosphorylates the MEF2s and enhances transcriptional activity of MEF2A, MEF2C but not MEF2D (By similarity). Interacts with SGK1 (By similarity). Interacts with PML (By similarity). Interacts (via N-terminal half) with HSP90AB1-CDC37 chaperone complex in resting cells; the interaction is MAP2K5-independent and prevents MAPK7 from ubiquitination and proteasomal degradation (PubMed:23428871).|||May not have a kinase activity. May not stimulate MEF2C activity. May function as dominant negative inhibitor of the ERK5 signaling pathway.|||Nucleus|||PML body|||Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression (By similarity). Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction (By similarity).|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.|||The second proline-rich region may interact with actin targeting the kinase to a specific location in the cell.|||Unable to translocate from the cytoplasm to the nucleus. http://togogenome.org/gene/10090:Gemin8 ^@ http://purl.uniprot.org/uniprot/Q8BHE1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (By similarity). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (By similarity). Interacts with GEMIN6; the interaction is direct (By similarity). Interacts with GEMIN7; the interaction is direct (By similarity). Interacts with SMN1; the interaction is direct (By similarity). Interacts with GEMIN4; the interaction is direct (By similarity).|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (By similarity).|||Widely expressed in embryonic tissues (at protein level).|||gem http://togogenome.org/gene/10090:Moxd1 ^@ http://purl.uniprot.org/uniprot/Q9CXI3 ^@ Cofactor|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the copper type II ascorbate-dependent monooxygenase family.|||Binds 2 copper ions per subunit.|||Broadly exprressed, with highest levels in salivary gland and ovary.|||Endoplasmic reticulum membrane|||N-glycosylated. http://togogenome.org/gene/10090:Ptpn12 ^@ http://purl.uniprot.org/uniprot/P35831 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.|||Complete embryonic lethality at 9.5 to 10.5 dpc. Heterozygous mice have no obvious phenotype.|||Cytoplasm|||Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades (PubMed:17070019). Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2. Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (By similarity).|||Interacts with PSTPIP1 and TGFB1I1 (PubMed:10092676, PubMed:11711533). Interacts with PTK2B/PYK2 (PubMed:12674328). Interacts with LPXN (PubMed:12674328, PubMed:15786712). Interacts with SORBS2; this interaction greatly enhances WASF1 dephosphorylation and might mediate partial translocation to focal adhesion sites (By similarity).|||Phosphorylated by STK24/MST3 and this results in inhibition of its activity.|||focal adhesion|||podosome http://togogenome.org/gene/10090:Car8 ^@ http://purl.uniprot.org/uniprot/P28651 ^@ Caution|||Function|||Similarity|||Tissue Specificity ^@ Although it belongs to the alpha-carbonic anhydrase family, Arg-117 is present instead of the conserved His which is a zinc-binding residue. It is therefore expected that this protein lacks carbonic anhydrase activity.|||Belongs to the alpha-carbonic anhydrase family.|||Does not have a carbonic anhydrase catalytic activity.|||Expressed only in Purkinje cells. http://togogenome.org/gene/10090:Gyg ^@ http://purl.uniprot.org/uniprot/Q9R062 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 8 family. Glycogenin subfamily.|||Divalent metal ions. Required for self-glucosylation. Manganese is the most effective.|||Homodimer. Interacts (via C-terminus) with glycogen synthase GYS1 (By similarity). Interacts (via C-terminus) with GYS2; required for GYS2-mediated glycogen synthesis (PubMed:24982189).|||Phosphorylated.|||Self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase.|||Self-glycosylated by the transfer of glucose residues from UDP-glucose to itself, forming an alpha-1,4-glycan of around 10 residues attached to Tyr-195.|||Skeletal muscle, heart, to a lesser extent in kidney, lung and brain. http://togogenome.org/gene/10090:Rps6kb1 ^@ http://purl.uniprot.org/uniprot/Q3UXD8|||http://purl.uniprot.org/uniprot/Q8BSK8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1 (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Cytoplasm|||Impairment of body growth. Lethal in combination with Rps6kb2 deficiency.|||Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with TRAF4. Interacts with POLDIP3. Interacts (via N-terminus) with IER5.|||Mitochondrion|||Mitochondrion outer membrane|||Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism. Activated by phosphorylation at Thr-252 by PDPK1. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (By similarity).|||Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:11493700, PubMed:15060135). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:11493700). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (By similarity). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (By similarity). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (By similarity). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (By similarity). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (By similarity). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (By similarity). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (By similarity). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (PubMed:11493700). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (By similarity). The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function (By similarity). Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (By similarity). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (By similarity). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239).|||The TOS (TOR signaling) motif is essential for activation by mTORC1.|||The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop.|||synaptosome http://togogenome.org/gene/10090:Def8 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZW6|||http://purl.uniprot.org/uniprot/G3X9U5|||http://purl.uniprot.org/uniprot/Q99J78 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Abundantly expressed during embryogenesis.|||Abundantly expressed in peripheral blood leukocytes. Highly expressed in B-cells. Also present in lymph node and appendix. Down-regulated upon macrophage/granulocyte differentiation. Weakly expressed in bone marrow and spleen. Weakly or not expressed in thymus and fetal liver.|||Belongs to the DEF8 family.|||Interacts (via C-terminus) with PLEKHM1; this interaction is weak but increased in a RAB7A-dependent manner (PubMed:27777970).|||Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (PubMed:27777970). Involved in bone resorption (PubMed:27777970). http://togogenome.org/gene/10090:Zfp37 ^@ http://purl.uniprot.org/uniprot/P17141 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in testis and brain.|||May have a role in regulating spermiogenesis.|||Nucleus http://togogenome.org/gene/10090:Or6e1 ^@ http://purl.uniprot.org/uniprot/Q9Z1V0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. Activated by (-)-citronellal and to a lesser extent by (+)-citronellal. Not activated by carvone or limonene. http://togogenome.org/gene/10090:Vmn1r165 ^@ http://purl.uniprot.org/uniprot/D3YTY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Comp ^@ http://purl.uniprot.org/uniprot/Q9R0G6 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the thrombospondin family.|||Binds 11-14 calcium ions per subunit.|||Each of the eight TSP type-3 repeats binds two calcium ions. The TSP C-terminal domain binds three calcium ions.|||Expressed in cartilage, including nasal, knee epiphyseal and rib tissues. Abundantly expressed in chondrocyte and tendon extracellular matrix (at protein level) (PubMed:32686688).|||In knee epiphyseal cartilage, expression is detected from 12.5 dpc onwards, with significant up-regulation at 16.5 dpc and again at postnatal day 5. Expressed at least until 10 months of age.|||Pentamer; disulfide-linked. Exists in a more compact conformation in the presence of calcium and shows a more extended conformation in the absence of calcium. Interacts with ITGB3, ITGA5 and FN1. Binding to FN1 requires the presence of divalent cations (Ca(2+), Mg(2+) or Mn(2+)). The greatest amount of binding is seen in the presence of Mn(2+). Interacts with MATN1, MATN3, MATN4 and ACAN. Binds heparin, heparan sulfate and chondroitin sulfate. EDTA dimishes significantly its binding to ACAN and abolishes its binding to MATN3, MATN4 and chondroitin sulfate. Interacts with collagen I, II and IX, and interaction with these collagens is dependent on the presence of zinc ions. Interacts with ADAMTS12 (By similarity). Interacts with ITGA7 (By similarity).|||Plays a role in the structural integrity of cartilage via its interaction with other extracellular matrix proteins such as the collagens and fibronectin (PubMed:32686688). Can mediate the interaction of chondrocytes with the cartilage extracellular matrix through interaction with cell surface integrin receptors. Could play a role in the pathogenesis of osteoarthritis. Potent suppressor of apoptosis in both primary chondrocytes and transformed cells. Suppresses apoptosis by blocking the activation of caspase-3 and by inducing the IAP family of survival proteins (BIRC3, BIRC2, BIRC5 and XIAP) (By similarity). Essential for maintaining a vascular smooth muscle cells (VSMCs) contractile/differentiated phenotype under physiological and pathological stimuli. Maintains this phenotype of VSMCs by interacting with ITGA7 (By similarity).|||The TSP C-terminal domain mediates interaction with FN1 and ACAN.|||The cell attachment motif mediates the attachment to chondrocytes. It mediates the induction of both the IAP family of survival proteins and the antiapoptotic response.|||extracellular matrix http://togogenome.org/gene/10090:Nlrp1b ^@ http://purl.uniprot.org/uniprot/A1Z198 ^@ Activity Regulation|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome (By similarity). Nlrp1b inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in a ternary complex, thereby preventing Nlrp1b oligomerization and activation (By similarity). Nlrp1b inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity). May be activated by Toxoplasma gondii, although at a lower extent than allele 1 (PubMed:24218483). Not activated by cleavage by B.anthracis lethal toxin (LT) endopeptidase (PubMed:16429160, PubMed:21170303, PubMed:24492532, PubMed:31383852). May be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561).|||Acts as the sensor component of the Nlrp1b inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (By similarity). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (By similarity). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals: in response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the inflammasome directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (By similarity). In the absence of GSDMD expression, the Nlrp1b inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME) (By similarity). Activation of Nlrp1b inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (By similarity). Contrary to Nlrp1b allele 1, allele 2 is not activated by Bacillus anthracis lethal toxin (PubMed:16429160, PubMed:21170303, PubMed:24492532).|||Autocatalytically cleaved. Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal parts remain associated non-covalently.|||Belongs to the NLRP family.|||Constitutes the active part of the Nlrp1b inflammasome. In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus), preventing activation of the Nlrp1b inflammasome. In response to pathogen-associated signals, the N-terminal part of Nlrp1b is degraded by the proteasome, releasing this form, which polymerizes to form the Nlrp1b inflammasome complex: the Nlrp1b inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis.|||Constitutes the precursor of the Nlrp1b inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals.|||Inflammasome|||Interacts with DPP9; leading to inhibit activation of the inflammasome (By similarity). DPP9 acts via formation of a ternary complex, composed of a DPP9 homodimer, one full-length Nlrp1b protein, and one cleaved C-terminus of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) (By similarity). Interacts with DPP8; leading to inhibit activation of the inflammasome, probably via formation of a ternary complex with DPP8 (By similarity). Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3). Interacts with NOD2; this interaction may increase IL1B release (By similarity). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to B.anthracis lethal toxin (By similarity). Interacts with MEFV; this interaction targets Nlrp1b to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity).|||Interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus) in absence of pathogens and other damage-associated signals.|||Interacts with the N-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, N-terminus) in absence of pathogens and other damage-associated signals. Homomultimer; forms the Nlrp1b inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals. The Nlrp1b inflammasome polymeric complex directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC. Interacts (via CARD domain) with CASP1 (via CARD domain); leading to CASP1 activation.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nlrp1b gene is extremely polymorphic. 5 alleles have been described in 18 inbred strains: 1 (AC Q2LKW6), 2 (this entry), 3 (AC Q2LKV5), 4 (AC Q2LKV2) and 5 (AC Q0GKD5). These alleles define susceptibility to B.anthracis lethal toxin (LT). Alleles 2 (carried by A/J, C57BL/6J and I/LnJ), 3 (AKR/J, NOD/LtJ and SJL/J) or 4 (DBA/2J, P/J and SM/J) are not activated by LT. Alleles 1 (carried by 129S1/SvImJ, BALB/cJ, C3H/HeJ, CBA/J, FVB/NJ, NON/ShiLtJ, NZO (NZO/HlLtJ) and SWR/J strains) and 5 (CAST/EiJ) confer macrophage susceptibility to LT. In susceptible strains, infection by Bacillus anthracis leads to IL1B release, neutrophil recruitment and macrophage pyroptosis. This early inflammatory response confers increased resistance to infection (PubMed:16429160). The sequence shown in this entry is that of allele 2 (PubMed:16429160).|||Regulatory part that prevents formation of the Nlrp1b inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of Nlrp1b (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), preventing activation of the Nlrp1b inflammasome. In response to pathogen-associated signals, this part is ubiquitinated by the N-end rule pathway and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1b inflammasome.|||The C-terminal part of Nlrp1b oligomerizes to form the core of the Nlrp1b inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments. The UPA region reduces the threshold needed for filament formation and signaling.|||The CARD domain is involved in the interaction with CASP1 and CASP4/CASP11.|||The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding. In allele 1, autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated (By similarity). It is not known whether this modification occurs in allele 2 (Probable).|||The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain.|||Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c, have been identified. Nlrp1c is predicted to be a pseudogene.|||Ubiquitinated by the N-end rule pathway in response to pathogens and other damage-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1b, C-terminus), which polymerizes and forms the Nlrp1b inflammasome.|||Up-regulated transiently following acute injury of the sciatic nerve with a peak after 44 hours.|||Widely expressed, including in macrophages and, at lower levels, in the peripheral nervous system, including in the sciatic nerve, Schwann cells, sensory neurons and motor neurons.|||cytosol http://togogenome.org/gene/10090:Plekhh2 ^@ http://purl.uniprot.org/uniprot/Q8C115 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in the kidney and testis. Expressed in the kidney exclusively by glomerular podocytes.|||In the kidney glomerulus may play a role in linking podocyte foot processes to the glomerular basement membrane. May be involved in stabilization of F-actin by attenuating its depolymerization. Can recruit TGFB1I1 from focal adhesions to podocyte lamellipodia.|||Self-associates. Interacts with TGFB1I1.|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Elovl6 ^@ http://purl.uniprot.org/uniprot/Q920L5 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ELO family. ELOVL6 subfamily.|||By SREBF1.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that elongates fatty acids with 12, 14 and 16 carbons with higher activity toward C16:0 acyl-CoAs. Catalyzes the synthesis of unsaturated C16 long chain fatty acids and, to a lesser extent, C18:0 and those with low desaturation degree. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.|||Endoplasmic reticulum membrane|||Highly expressed in adrenal gland, liver, white adipose tissue (WAT), adult and fetal brain, cerebellum, spinal cord, testis, skin and peripheral nerve; where lipogenesis and steroidogenesis are active. Weakly expressed in kidney, heart, skeletal muscle, lung, and spleen.|||Homozygous knockout mice lacking Elovl6 are partially viable and surviving animals are fertile. Mutant mice appear grossly normal and slightly but significantly leaner than wild-type littermates. Hepatic concentrations of stearate (C18:0) and oleate (C18:1n-9) are lowered, whereas those of palmitate (C16:0) and palmitoleate (C16:1n7) are increased. Elovl6 deletion abrogates the development of diet-induced insulin resistance.|||N-Glycosylated.|||The reaction is stimulated by the presence of HSD17B12, the enzyme catalyzing the second step of the elongation cycle. http://togogenome.org/gene/10090:Usp6nl ^@ http://purl.uniprot.org/uniprot/Q80XC3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a GTPase-activating protein for RAB5A and RAB43. Involved in receptor trafficking. In complex with EPS8 inhibits internalization of EGFR. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for structural integrity of the Golgi complex (By similarity).|||Cytoplasmic vesicle|||Golgi apparatus|||Interacts with EPS8. http://togogenome.org/gene/10090:Ndufb11b ^@ http://purl.uniprot.org/uniprot/Q9CQ68 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB11 subunit family.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Atp2a3 ^@ http://purl.uniprot.org/uniprot/E9Q559|||http://purl.uniprot.org/uniprot/Q3U1K2|||http://purl.uniprot.org/uniprot/Q3U6T4|||http://purl.uniprot.org/uniprot/Q64518|||http://purl.uniprot.org/uniprot/Q8C213|||http://purl.uniprot.org/uniprot/Q8R0X5 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.|||Catalyzes the hydrolysis of ATP coupled with the transport of calcium.|||Endoplasmic reticulum membrane|||Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).|||Interacts with sarcolipin (SLN) (By similarity). Interacts with phospholamban (PLN) (By similarity). Interacts with myoregulin (MRLN). Interacts with DWORF (By similarity). Interacts with VMP1 (By similarity). Interacts with TUNAR; the interaction occurs at low levels in low glucose conditions and is increased by high glucose levels (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Sarcoplasmic reticulum membrane|||This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction. http://togogenome.org/gene/10090:Parp12 ^@ http://purl.uniprot.org/uniprot/Q8BZ20 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Auto-mono-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.|||Nucleus http://togogenome.org/gene/10090:Odf3b ^@ http://purl.uniprot.org/uniprot/Q5M8M2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CIMAP family.|||flagellum http://togogenome.org/gene/10090:Ginm1 ^@ http://purl.uniprot.org/uniprot/Q91WR6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Stx1b ^@ http://purl.uniprot.org/uniprot/P61264 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Interacts with OTOF. Interacts with SYT6 and SYT8; the interaction is Ca(2+)-dependent.|||Membrane|||Phosphorylated by CK2.|||Potentially involved in docking of synaptic vesicles at presynaptic active zones (By similarity). May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. http://togogenome.org/gene/10090:Afap1l1 ^@ http://purl.uniprot.org/uniprot/Q8BZI0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CTTN.|||May be involved in podosome and invadosome formation.|||invadopodium|||podosome|||stress fiber http://togogenome.org/gene/10090:Accs ^@ http://purl.uniprot.org/uniprot/A2AIG8 ^@ Caution|||Function|||Similarity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Does not catalyze the synthesis of 1-aminocyclopropane-1-carboxylate but is capable of catalyzing the deamination of L-vinylglycine.|||Similar to plant 1-aminocyclopropane-1-carboxylate synthases but lacks a number of residues which are necessary for activity. http://togogenome.org/gene/10090:Vmn2r43 ^@ http://purl.uniprot.org/uniprot/Q80Z08 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Scn5a ^@ http://purl.uniprot.org/uniprot/A0A0R4J1M7|||http://purl.uniprot.org/uniprot/K3W4N7|||http://purl.uniprot.org/uniprot/Q9JJV9 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily.|||Cell junction|||Cell membrane|||Expressed in the myocardium.|||Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 (PubMed:9412493). Interacts with NEDD4, NEDD4L, WWP2 and GPD1L (By similarity). Interacts with CALM (By similarity). Interacts with FGF13; the interaction is direct and may regulate SNC5A density at membranes and function (PubMed:21817159). Interacts with FGF12 and FGF14 (By similarity). Interacts with ANK3 (By similarity). Interacts with PKP2 (via N-terminus) (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 868) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Membrane|||Phosphorylation at Ser-1505 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents (By similarity). Regulated through phosphorylation by CaMK2D (PubMed:17124532).|||T-tubule|||The IQ domain mediates association with calmodulin.|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.|||This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:11834499, PubMed:23420830). It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (By similarity).|||Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2.|||perinuclear region http://togogenome.org/gene/10090:Ankrd46 ^@ http://purl.uniprot.org/uniprot/Q8BTZ5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Gm9376 ^@ http://purl.uniprot.org/uniprot/G3UW68 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Or5p56 ^@ http://purl.uniprot.org/uniprot/Q8VGI6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Timm44 ^@ http://purl.uniprot.org/uniprot/O35857 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tim44 family.|||Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner (PubMed:31618756). Recruits mitochondrial HSP70 to drive protein translocation into the matrix using ATP as an energy source (By similarity).|||Mitochondrion inner membrane|||Probable component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19 (By similarity). The complex interacts with the TIMM23 component of the TIM23 complex (PubMed:31618756). Interacts with SLC25A4/ANT1 and SLC25A5/ANT2; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756). http://togogenome.org/gene/10090:Dtx3l ^@ http://purl.uniprot.org/uniprot/Q3UIR3 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated.|||Belongs to the Deltex family.|||Binding to PARP9 enhances DTX3L catalytic activity.|||Cytoplasm|||Developmentally regulated. Expressed prominently in the thymus and specific regions of the brain, and more weakly expressed in the gut. In adults, highly expressed in the thymus and intestine.|||E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses. Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4. In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1). The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. By monoubiquitinating histone H2B H2BC9/H2BJ and thereby promoting chromatin remodeling, positively regulates STAT1-dependent interferon-stimulated gene transcription and thus STAT1-mediated control of viral replication. Independently of its catalytic activity, promotes the sorting of chemokine receptor CXCR4 from early endosome to lysosome following CXCL12 stimulation by reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination of endosomal sorting complex required for transport ESCRT-0 components HGS and STAM. In addition, required for the recruitment of HGS and STAM to early endosomes.|||Early endosome membrane|||Homodimer and heterodimer. Can heterodimerize with DTX1, enhancing its ubiquitin ligase activity in vitro. Interacts (via N-terminus) with ADP ribosyltransferase PARP9/BAL1 (via PARP catalytic domain) forming a stable complex; the interaction is required to activate PARP9 but is dispensable for DTX3L catalytic activity. Forms a complex with STAT1 and PARP9 independently of IFNB1 or IFNG-mediated STAT1 'Tyr-701' phosphorylation. Found in a complex with PARP9, STAT1 and H2BC9. Found in a complex with E3 ligase ITCH and ESCRT-0 components HGS and STAM. Interacts (via C-terminus) with ITCH; the interaction is increased upon CXCL12 stimulation and inhibits ITCH catalytic activity; the interaction is direct. Interacts with HGS and STAM; the interaction brings together HGS and STAM and promotes their recruitment to early endosomes.|||Lysosome membrane|||Nucleus http://togogenome.org/gene/10090:Rspo4 ^@ http://purl.uniprot.org/uniprot/Q0P5Y9|||http://purl.uniprot.org/uniprot/Q8BJ73 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway.|||Belongs to the R-spondin family.|||Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6.|||Secreted|||The FU repeat is required for activation and stabilization of beta-catenin. http://togogenome.org/gene/10090:Tcaim ^@ http://purl.uniprot.org/uniprot/Q66JZ4 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in peripheral blood leukocytes, mainly in T-lymphocytes.|||May regulate T-cell apoptosis.|||Mitochondrion|||Up-regulated during induction and maintenance of graft acceptance and down-regulated during graft rejection. http://togogenome.org/gene/10090:Muc1 ^@ http://purl.uniprot.org/uniprot/Q02496 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Cytoplasm|||Dual palmitoylation on cysteine residues in the CQC motif is required for recycling from endosomes back to the plasma membrane.|||Expressed in a variety of epithelial tissues.|||Nucleus|||O-glycosylation sites are annotated in first sequence repeat only. Residues at similar position are probably glycosylated in all repeats.|||Phosphorylated on tyrosines and serine residues in the C-terminal. Phosphorylation on tyrosines in the C-terminal increases the nuclear location of MUC1 and beta-catenin. Phosphorylation by PKC delta induces binding of MUC1 to beta-catenin/CTNNB1 and thus decreases the formation of the beta-catenin/E-cadherin complex. Src-mediated phosphorylation inhibits interaction with GSK3B. Csk- or Src- or EGFR-mediated phosphorylation on Tyr-604 increases binding to beta-catenin/CTNNB1. GSK3B-mediated phosphorylation on Ser-602 decreases this interaction but restores the formation of the beta-cadherin/E-cadherin complex. On T-cell receptor activation, phosphorylated by LCK. PDGFR-mediated phosphorylation increases nuclear colocalization of MUC1CT and CTNNB1 (By similarity).|||Probably both N- and extensively O-glycosylated (in repeat region).|||Proteolytic cleavage in the SEA domain occurs in the endoplasmic reticulum by an autoproteolytic mechanism and requires the full-length SEA domain as well as requiring a Ser, Thr or Cys residue at the P + 1 site. Ectodomain shedding is mediated by ADAM17 in uterine epithelial cells (By similarity).|||The alpha subunit forms a tight, non-covalent heterodimeric complex with the proteolytically-released beta-subunit. Binds directly the SH2 domain of GRB2, and forms a MUC1/GRB2/SOS1 complex involved in RAS signaling. The cytoplasmic tail (MUC1CT) interacts with several proteins such as SRC, CTNNB1 and ERBs. Interaction with the SH2 domain of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and, to a much lesser extent, the interaction with ERBB3 and ERBB4. Interacts with P53 in response to DNA damage. Interacts with KLF4. Interacts with estrogen receptor alpha/ESR1, through its DNA-binding domain, and stimulates its transcription activity. Binds ADAM17 (By similarity). C.jejeuni adheres to gastric epithelial MUC1 and modulates its transcription.|||The alpha subunit has cell adhesive properties. Can act both as an adhesion and an anti-adhesion protein. May provide a protective layer on epithelial cells against bacterial and enzyme attack.|||The beta subunit contains a C-terminal domain which is involved in cell signaling, through phosphorylations and protein-protein interactions. Modulates signaling in ERK, Src and NF-kappaB pathways. In activated T-cells, influences directly or indirectly the Ras/MAPK pathway. Regulates P53-mediated transcription and determines cell fate in the genotoxic stress response. Binds, together with KLF4, the PE21 promoter element of P53 and represses P53 activity. http://togogenome.org/gene/10090:Fbxo47 ^@ http://purl.uniprot.org/uniprot/A2A6H3 ^@ Function|||Subunit ^@ Part of a SCF (SKP1-cullin-F-box) protein ligase complex.|||Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. http://togogenome.org/gene/10090:Ifnz ^@ http://purl.uniprot.org/uniprot/Q8BQT1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Pm20d1 ^@ http://purl.uniprot.org/uniprot/Q8C165 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M20A family.|||Binds 2 Zn(2+) ions per subunit.|||Genetic ablation causes tissue-specific bidirectional dysregulation of several N-acyl amino acids (PubMed:29967167, PubMed:32271712). Locomotor activity and resting energy requirements (RER) are slightly increased and decreased, respectively, in PM20D1-KO mice on chow diet, while diet-induced obesity conditions produce a marked impairment in glucose homeostasis and insulin sensitivity in these mice. They also exhibit enhanced defense of body temperature in cold, and antinociceptive behaviors selectively in response to chemical and inflammatory pain stimuli while maintaining normal thermal pain sensation and normal movement (PubMed:29967167).|||In addition to being detected in blood (at protein level), PM20D1 is also highly expressed in other tissues including brown adipocytes, liver and kidney (PubMed:27374330, PubMed:29967167). It is also expressed in small intestine, large intestine, heart and pancreas (PubMed:29967167).|||Lipoproteins are powerful coactivators of PM20D1 activity in vitro and NAA biosynthesis in vivo.|||Overexpression in mice blunts high fat diet-induced increase in fat mass and associated weight gain (PubMed:27374330). Free NAAs represent the biologically active form of these circulating molecules, and the circulating NAAs bioactivity is determined by plasma protein binding (PubMed:32402239).|||Secreted|||Secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase. It condenses free fatty acids and free amino acids to generate NAAs and bidirectionally catalyzes the reverse hydrolysis reaction (PubMed:27374330, PubMed:29533650, PubMed:29967167, PubMed:32271712, PubMed:32402239) (Probable). Some of these NAAs stimulate oxidative metabolism via mitochondrial uncoupling, increasing energy expenditure in a UPC1-independent manner. Thereby, this secreted protein may indirectly regulate whole body energy expenditure (PubMed:27374330, PubMed:29967167, PubMed:32271712). PM20D1 circulates in tight association with both low- and high-density (LDL and HDL,respectively) lipoprotein particles (PubMed:32402239).|||Up-regulated in adipose tissue upon cold exposure. http://togogenome.org/gene/10090:Srm ^@ http://purl.uniprot.org/uniprot/Q543H0|||http://purl.uniprot.org/uniprot/Q64674 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Belongs to the spermidine/spermine synthase family.|||Catalyzes the production of spermidine from putrescine and decarboxylated S-adenosylmethionine (dcSAM). Has a strong preference for putrescine as substrate, and has very low activity towards 1,3-diaminopropane. Has extremely low activity towards spermidine (By similarity).|||Homodimer or homotetramer.|||The activity is thought to be regulated mainly by the availability of decarboxylated S-adenosylmethionine. http://togogenome.org/gene/10090:Gm2030 ^@ http://purl.uniprot.org/uniprot/D3Z7C4 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Or7e165 ^@ http://purl.uniprot.org/uniprot/Q7TRF6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nmrk1 ^@ http://purl.uniprot.org/uniprot/Q91W63 ^@ Function|||Similarity|||Subunit ^@ Belongs to the uridine kinase family. NRK subfamily.|||Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN).|||Monomer. http://togogenome.org/gene/10090:B3gat1 ^@ http://purl.uniprot.org/uniprot/Q9CW73 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 43 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer. Interacts with SAR1A.|||Involved in the biosynthesis of L2/HNK-1 carbohydrate epitope on glycoproteins. Can also play a role in glycosaminoglycan biosynthesis. Substrates include asialo-orosomucoid (ASOR), asialo-fetuin, and asialo-neural cell adhesion molecule. Requires sphingomyelin for activity: stearoyl-sphingomyelin was the most effective, followed by palmitoyl-sphingomyelin and lignoceroyl-sphingomyelin. Activity was demonstrated only for sphingomyelin with a saturated fatty acid and not for that with an unsaturated fatty acid, regardless of the length of the acyl group.|||Secreted|||The soluble form derives from the membrane form by proteolytic processing. http://togogenome.org/gene/10090:Tsga10 ^@ http://purl.uniprot.org/uniprot/Q6NY15 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CEP135/TSGA10 family.|||Cytoplasm|||First detected at 7.5 dpc (PubMed:16643851). Tends to be expressed weakly during the early stages of embryogenesis. Expression increases over time in different growing and differentiating tissues, including brain (11.5 dpc), vertebrae (14.5 dpc), primordia of vibrissae follicle (15.5 dpc), intestinal sub-endothelium (16.5 dpc), pancreas (16.5 dpc), eyeball (16.5 dpc), liver (16.5 dpc), telencephalon (18.5 dpc) (PubMed:16643851). In the developing neural tube at 8.5-9.0 dpc, preferentially expressed in cells with one or more neuronal extensions (PubMed:16643851). During spermatogenesis, weakly detected in primary spermatocytes, but expression increases, reaching strong levels in elongated spermatids (stage V) and mature sperm (at protein level) (PubMed:16643851).|||Interacts with HIF1A.|||Plays a role in spermatogenesis (PubMed:14585816). When overexpressed, prevents nuclear localization of HIF1A (PubMed:16777103).|||Predominantly expressed in testis, in spermatozoa (at protein level) (PubMed:14585816, PubMed:16643851). Not detected in Leydig cells (PubMed:16643851). The N-terminal 27-kDa fragment is also detected in liver, while the C-terminal 55-kDa fragment is also found retina, brain and kidney (at protein level) (PubMed:16643851).|||Processed into N-terminal 27-kDa and C-terminal 55-kDa fragments.|||centriole http://togogenome.org/gene/10090:Dipk2a ^@ http://purl.uniprot.org/uniprot/Q3USZ8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ As early as 12.5 dpc to 16.5 dpc, intense expression is restricted to mesenchymal condensations, which form the different cartilage elements of the developing skeleton. At 12.5 dpc, strongly expressed in all vertebrae, heart ventricle, dental follicle, interdigital tissue, tongue and cartilages of the basioccipital bone, maxilla, mandible and the region of the future nasal septum. At 14.5 and 16.5 dpc, expressed in ribs, long bones, interdigital tissue, metatarsals, dental follicle, cartilages of the mandible and nasal septum as well as vertebrae with stronger expression in posterior vertebrae. At 16.5 dpc, also expressed in paw bones and, in vertebrae, the expression is limited to mainly columnar, proliferating chondrocytes. At 4 days postnatal, intense expression in nasal cartilages, hair, dental and vibrissa follicles.|||Belongs to the DIPK family.|||COPI-coated vesicle|||Expressed in heart, brain, liver, spleen, kidney, lung, thymus, testis, ovary and muscle.|||Golgi apparatus|||May play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PI3-kinase signaling cascade.|||Secreted http://togogenome.org/gene/10090:Paip1 ^@ http://purl.uniprot.org/uniprot/Q8VE62 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a coactivator in the regulation of translation initiation of poly(A)-containing mRNAs. Its stimulatory activity on translation is mediated via its action on PABPC1. Competes with PAIP2 for binding to PABPC1. Its association with EIF4A and PABPC1 may potentiate contacts between mRNA termini. May also be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (By similarity).|||Cytoplasm|||Interacts with the RRM1-RRM2 and C-terminus regions of PABPC1 in a 1:1 stoichiometry. Interacts with EIF4A (By similarity).|||Only the PABPC1-interacting motif-1 (PAM1) stimulates translation initiation. http://togogenome.org/gene/10090:Sgca ^@ http://purl.uniprot.org/uniprot/P82350 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sarcoglycan alpha/epsilon family.|||Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.|||Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans. Interacts with the syntrophin SNTA1.|||In the embryo, expression begins at day 14 and coincides with the onset of primary myogenesis.|||Striated muscle, both skeletal and cardiac.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Kansl1l ^@ http://purl.uniprot.org/uniprot/Q5DTI6 ^@ PTM ^@ Acetylated on lysine residues by KAT8 upon ionizing radiation-induced DNA damage; deacetylated by HDAC3. http://togogenome.org/gene/10090:Iho1 ^@ http://purl.uniprot.org/uniprot/Q6PDM4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Detected in spermatocytes and testis (at protein level) (PubMed:27723721).|||Interacts with HORMAD1 (PubMed:27723721). Interacts with REC114 (PubMed:27723721). Part of the MCD recombinosome complex, at least composed of IHO1, REC114 and MEI4 (PubMed:27723721). Interacts with ANKRD31 (PubMed:31000436).|||Meiosis-specific.|||Mice develop normally without obvious somatic defects but males and females are sterile due to defects in homologous synapsis (PubMed:27723721). Oocytes are depleted in six-week-old females and spermatocytes in males undergo apoptosis at a stage equivalent to wild-type mid-pachytene (PubMed:27723721). Complete synapsis is never observed and incomplete synaptonemal complexes are detected in meiocytes equivalent to late-zygotene and pachytene (PubMed:27723721).|||Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination (PubMed:27723721). Probably acts by forming a complex with MEI4 and REC114, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis (PubMed:27723721). Not required for HORMAD1 functions in pairing-independent synaptonemal complex formation, ATR recruitment to unsynapsed axes, meiotic silencing of unsynapsed chromatin (MSUC) or meiotic surveillance (PubMed:27723721). http://togogenome.org/gene/10090:Grb2 ^@ http://purl.uniprot.org/uniprot/Q3U1Q4|||http://purl.uniprot.org/uniprot/Q3U5I5|||http://purl.uniprot.org/uniprot/Q60631 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.|||Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (By similarity). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (PubMed:8943348). Interacts with IRS4 (when Tyr-phosphorylated) (PubMed:11113178). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains (By similarity). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (By similarity). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (By similarity). Interacts with phosphorylated MET (By similarity). Interacts with phosphorylated TOM1L1 (PubMed:11711534). Interacts with the phosphorylated C-terminus of SH2B2 (By similarity). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:16249387, PubMed:14610044, PubMed:15477350, PubMed:15477348, PubMed:22561606). Interacts with NISCH, PTPNS1 and REPS2 (By similarity). Interacts with syntrophin SNTA1 (PubMed:11551227). Interacts (via SH3 domains) with REPS1 (PubMed:9395447). Interacts (via SH3 domains) with PIK3C2B (By similarity). Interacts with CBL and CBLB (By similarity). Interacts with AJUBA and CLNK (PubMed:10330178, PubMed:11463797). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (PubMed:10521483). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (By similarity). Interacts with PTPN11 (PubMed:8943348). Interacts with PRNP (PubMed:11571277). Interacts with RALGPS1 (By similarity). Interacts also with HCST (PubMed:16582911). Interacts with KDR (PubMed:16966330). Interacts with FLT1 (tyrosine-phosphorylated) (PubMed:9722576). Interacts with GAPT and PTPRE (By similarity). Interacts (via SH2 domain) with KIF26A (By similarity). Interacts (via SH3 2) with GAB2 (PubMed:10068651). Interacts with ADAM15 (By similarity). Interacts with THEMIS2 (PubMed:20644716). Interacts (via SH2 domain) with AXL (phosphorylated) (By similarity). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:10377264). Interacts with PTPRJ and BCR (By similarity). Interacts with PTPN23 (By similarity). Interacts with FLT4 (tyrosine phosphorylated) (By similarity). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:12925710). Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with ERBB4 (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:7997267). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (By similarity). Interacts (via SH2-domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-58' (PubMed:21930792, PubMed:28098138, PubMed:28290451). Interacts (via SH3 domains) with GAREM1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (By similarity). Interacts with DAB2 (PubMed:9569023). Interacts with TESPA1 (By similarity). Interacts with THEMIS (PubMed:19597498, PubMed:19597497, PubMed:19805304, PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (PubMed:22561606). Interacts with CD28 (By similarity). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (PubMed:21543326). Interacts with ASAP3 (phosphorylated form) (By similarity). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064). Interacts with PTPRO (phosphorylated form) (PubMed:20398064). Interacts with PTPRB (phosphorylated form) (PubMed:20398064). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (By similarity). Interacts with DENND2B (By similarity). Interacts with SPRY2 (By similarity). Interacts with LRRC8A (PubMed:32930093). Interacts with PEAK1 (By similarity).|||Belongs to the GRB2/sem-5/DRK family.|||Cytoplasm|||Does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.|||Endosome|||Expressed in macrophages.|||Golgi apparatus|||Nucleus|||The SH3 domains mediate interaction with RALGPS1 and SHB. http://togogenome.org/gene/10090:Baalc ^@ http://purl.uniprot.org/uniprot/Q8VHV1 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At the mRNA level, predominantly expressed in the brain (PubMed:11707601). At the protein level, mainly expressed in muscle tissues. In skeletal muscles, expressed in cranial and facial muscles, muscles of the neck, back, thoracic wall, and thigh. Also found in the contractile myoepithelial cell layer of salivary glands. In smooth muscles, expressed in the gastric wall, uterus, urinary bladder, as well as in the muscular lining around seminiferous tubules, prostatic ducts, epididymis, vas deferens, walls of small blood vessels in the dermis, and fascial layers between muscle fibers, brain, and around the spinal cord. Strongly expressed in myocardium. High expression levels are observed in placental spongiotrophoblast and adjacent myometrium. Also expressed in bone marrow hematopoietic cells. In the mature thymus, expressed in rare scattered cells. Weakly expressed in the brain neuropil, particularly near the hippocampus, and spinal cord white matter. Not detected in skin keratinocytes or lung (at protein level) (PubMed:15749074).|||Cytoplasm|||During embryonic development, prominently expressed in muscle tissues, including myocardium, skeletal and smooth muscles, and weakly in the developing central nervous system (only in the neuropil). At 9 dpc, expressed in the wall and trabeculae of the developing heart tube, in the caudal end of the midline dorsal aorta, and a focal area of the mesenchyme around the developing brain. Weakly expressed in marginal and ependymal layers of the early neural tube. At 11-12.5 dpc, expression persists in the myocardium. Scattered signal in the mesoderm on either side of the developing neural tube. Also found in the region of dermatomyotomes. Appears to be associated with the early pre-muscle mesoderm and later with myoblasts and myocytes of the paravertebral, back, body wall and limb muscles. At 13-15 dpc, besides the myocardium, expression is seen in the skeletal muscles of the limbs, intercostal muscles, and the diaphragm, as well as in the developing muscle layer in the wall of the few intestinal coils present in the abdominal cavity. Also found in various components of the mesenchymal precartilage forming the framework of the cranium and the face, notably, the base of the skull, frontonasal process and parts of the primitive maxillary and mandibular processes. Around 13 dpc, detected in the brain lateral ventricles and the roof of the fourth ventricle. At 15 dpc, scattered groups of positive cells are observed in the liver, around the venous sinuses. Weakly expressed in the brain and spinal cord white matter. Prominent membrane expression in the choroid plexus and meninges. At 15-18 dpc, transiently expressed in the layers of ectodermal cells covering the embryo and in immature cells of the lung buds. From 16 dpc to postnatal day 2, no change in the basic pattern of expression (at protein level).|||Interacts with CAMK2A.|||May play a synaptic role at the postsynaptic lipid rafts possibly through interaction with CAMK2A.|||Membrane raft|||Palmitoylation and myristoylation target the protein to the lipid rafts.|||Postsynaptic density|||synaptosome http://togogenome.org/gene/10090:Foxj2 ^@ http://purl.uniprot.org/uniprot/Q9ES18 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed both maternally and zygotically. Zygotic expression first begins in 8-cell stage embryos, with expression increasing in blastocysts. In embryos, both cell layers of the blastocyst: the trophectoderm (TE) and the inner cell mass (ICM) show expression.|||Male germ-cell-specific conditional knockout results in complete male infertility and meiotic arrest in spermatocytes. Spermatocytes show aberrant chromosomal synapsis and DNA double-strand breaks (DSB) repair and significantly reduced expression of DSB repair-associated genes and meiotic arrest-related genes.|||Nucleus|||Spermtaocytes (at protein level). Expressed in adult brain, heart skeletal muscle, lung, kidney and gonads. Liver, small intestine, and spleen also show expression but at lower levels. In the testis, expressed from pachytene spermatocytes to round spermatids, but not in spermatogonia. In addition to the germ lineage, also expressed in Sertoli cells of the testis. In the ovary, only granulosa cells of the follicles show expression. In the brain, expressed in the piriform cortex, hippocampus, habenula and in the granula cell layer in the cerebellum.|||Transcriptional activator. Able to bind to two different type of DNA binding sites (By similarity). Plays an important role in spermatogenesis, especially in spermatocyte meiosis (PubMed:11025217, PubMed:15489334). http://togogenome.org/gene/10090:Or51v8 ^@ http://purl.uniprot.org/uniprot/F8VQI7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nudt12 ^@ http://purl.uniprot.org/uniprot/Q9DCN1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. NudC subfamily.|||Binds 1 zinc ion per subunit.|||Binds 3 Mg(2+) ions per subunit.|||Cytoplasm|||Cytoplasmic granule|||Expressed abundantly in the liver and kidney.|||Homodimer (PubMed:31101919). Homodimerization is essential for its catalytic activity and protein stability (By similarity). Interacts (via ANK repeats) with BLMH (By similarity).|||Peroxisome|||mRNA decapping enzyme that specifically removes the nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs by hydrolyzing the diphosphate linkage to produce nicotinamide mononucleotide (NMN) and 5' monophosphate mRNA (PubMed:31101919, PubMed:32432673). The NAD-cap is present at the 5'-end of some RNAs; in contrast to the canonical N7 methylguanosine (m7G) cap, the NAD cap promotes mRNA decay (PubMed:31101919). Preferentially acts on NAD-capped transcripts in response to nutrient stress (PubMed:31101919). Also acts on free nicotinamide adenine dinucleotide molecules: hydrolyzes NAD(H) into NMN(H) and AMP, and NADPH into NMNH and 2',5'-ADP (By similarity). May act to regulate the concentration of peroxisomal nicotinamide nucleotide cofactors required for oxidative metabolism in this organelle (By similarity). Regulates the levels of circadian clock components PER1, PER2, PER3 and CRY2 in the liver (PubMed:31875550). http://togogenome.org/gene/10090:Sppl2a ^@ http://purl.uniprot.org/uniprot/Q9JJF9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase A22B family.|||Glycosylated.|||Interacts with ITM2B.|||Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing. Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus. Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD). Essential for degradation of the invariant chain CD74 that plays a central role in the function of antigen-presenting cells in the immune system. Plays a role in the regulation of innate and adaptive immunity.|||Knockout mice increase susceptibility to mycobacterial infection after BCG administration compared to wild-type mice. Mutant animals have decreased numbers of DC2 dendritic cells (cDC2), a smaller sized IFNG+ CD4+ and CD8+ T cell fraction, and decreased production of IFNG by splenocytes compared to wild-type animals. They also have profound B cell deficiency due to CD74 NTF accumulation. The protein is required for optimal IFNG production by T cells after mycobacterial infection (PubMed:30127434). Mutant mice confirm depletion of conventional cDC2 cells in lymphatic tissues of null mice. Detailed studies of bone marrow-derived dendritic cells exposed to mycobacteria show enhanced secretion of Il1b, where production of Il10 and Ifnb1 is reduced. There are also some alterations in stimulation of pattern recognition receptors (PubMed:33239420).|||Late endosome membrane|||Lysosome membrane|||Membrane|||The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP (By similarity). The C-terminal tail is necessary for lysosomal transport (PubMed:21896273). http://togogenome.org/gene/10090:Tsc22d1 ^@ http://purl.uniprot.org/uniprot/D3YW86|||http://purl.uniprot.org/uniprot/D3Z0V7|||http://purl.uniprot.org/uniprot/E9QLZ1|||http://purl.uniprot.org/uniprot/H3BLI9|||http://purl.uniprot.org/uniprot/P62500|||http://purl.uniprot.org/uniprot/Q3UXU0 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TSC-22/Dip/Bun family.|||Cell membrane|||Cytoplasm|||Expressed in bone marrow cells (at protein level) (PubMed:19329776). Expressed in T-cells (PubMed:26752201). Expressed in the brain (PubMed:19329776).|||Expressed in the myoepithelial cells of the mammary gland ducts and alveoli, expression is consistent throughout pregnancy, lactation and involution (at protein level) (PubMed:19745830). Expressed in the cortex, medulla and papilla of the kidney (PubMed:17147695).|||Expressed in the myoepithelial cells of the mammary gland, expression significantly increases in the secretory luminal epithelium of the mammary gland at the initiation of involution, with levels decreasing from day 3 of involution onwards (at protein level) (PubMed:19745830). Expressed in the cortex, medulla and papilla of the kidney (PubMed:17147695).|||Forms a heterodimer with TSC22D4/THG1 (By similarity). Interacts with histone H1-2 (By similarity). Interacts with GNL3 (By similarity).|||Forms a heterodimer with TSC22D4/THG1.|||Forms homodimers (PubMed:12468551). Forms heterodimers (By similarity). Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1 (By similarity). Interacts with SMAD7; the interaction requires TGF-beta and the interaction is inhibited by TGFBR1 (By similarity). Interacts with TPT1/fortilin; interaction results in the destabilization of TSC22D1 protein and prevents TSC22D1-mediated apoptosis (By similarity). Interacts with SMAD4 (via N-terminus) (By similarity). Interacts with ACVRL1/ALK1, ACVR1/ALK2, BMPR1A/ALK3, ACVR1B/ALK4, BMPR1B/ALK6, ACVR2A/ACTRII, and BMPR2 (By similarity). Interacts with SMAD6 (By similarity). Interacts with TFE3; the interaction is enhanced in the presence of TGF-beta (PubMed:20713358).|||Increase in DNA synthesis in hematopoietic precursor cells from bone marrow, these cells have a greater ability to proliferate and repopulate an irradiated recipient.|||Induced by Tgfb1, Pparg and other growth factors (PubMed:1587811, PubMed:12468551). Induced by Tgfb3 in mammary gland cells (PubMed:19745830). Induced by TGF-beta via up-regulation of Ybx1 regulator miR-216a which decreases Ybx1 abundance and binding of Ybx1 to Tsc22d1 transcripts, thereby increasing Tsc22d1 translation (PubMed:20713358). Induced in the glomeruli of a diabetic mouse model (PubMed:20713358).|||May act to negatively regulate TGFB3 signaling and thereby inhibit cell death in mammary gland cells.|||Mitochondrion|||Nucleus|||Positively regulates cell death in response to TGFB3 during mammary gland involution.|||Transcriptional repressor (By similarity). Acts on the C-type natriuretic peptide (CNP) promoter (By similarity). Acts to promote CASP3-mediated apoptosis (By similarity). Positively regulates TGF-beta signaling by interacting with SMAD7 which inhibits binding of SMAD7 to TGFBR1, preventing recruitment of SMURF ubiquitin ligases to TGFBR1 and inhibiting SMURF-mediated ubiquitination and degradation of TGFBR1 (By similarity). Contributes to enhancement of TGF-beta signaling by binding to and modulating the transcription activator activity of SMAD4 (By similarity). Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TFE3 at E-boxes in the gene proximal promoter (PubMed:20713358). Plays a role in the repression of hematopoietic precursor cell growth (PubMed:19329776). Promotes IL2 deprivation-induced apoptosis in T-lymphocytes, via repression of TSC22D3/GILZ transcription and activation of the caspase cascade (PubMed:26752201). http://togogenome.org/gene/10090:Txndc16 ^@ http://purl.uniprot.org/uniprot/Q7TN22 ^@ Domain|||PTM|||Subcellular Location Annotation ^@ Contains a masked and non-functional KDEL endoplasmic reticulum retrieval motif.|||Endoplasmic reticulum lumen|||Glycosylated.|||Secreted http://togogenome.org/gene/10090:Rce1 ^@ http://purl.uniprot.org/uniprot/P57791 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase U48 family.|||Deubiquitination by USP17L2/USP17 negatively regulates the proteolytic activity toward Ras GTPases.|||Endoplasmic reticulum membrane|||Mice show defective Ras processing and mislocalization of Ras within cells.|||Proteolytically removes the C-terminal three residues of farnesylated and geranylated proteins. Seems to be able to process K-Ras, N-Ras, H-Ras, RAP1B and G-gamma-1 (By similarity).|||Ubiquitinated. Undergoes 'Lys-48'- and 'Lys-63'-linked ubiquitination. 'Lys-48' ubiquitination induces its degradation. Deubiquitinated by USP17L2/USP17 that cleaves 'Lys-63'-linked ubiquitin chains (By similarity). http://togogenome.org/gene/10090:Rufy2 ^@ http://purl.uniprot.org/uniprot/Q8R4C2 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit ^@ Expressed only at embryonic stages. Present at 12 dpc in primordial lung, cartilage and otic capsule (at protein level).|||Interacts with BMX.|||Nucleus http://togogenome.org/gene/10090:Zfp579 ^@ http://purl.uniprot.org/uniprot/Q80VM4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Serpinb1a ^@ http://purl.uniprot.org/uniprot/Q9D154 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Cytolytic granule|||Cytoplasm|||Early endosome|||Monomer. Interacts (via C-terminus) with CASP1 and CASP4 (via CARD domain); these interactions regulate the activity of inflammatory caspases.|||Mutant mice do not differ from wild-type in growth, litter size or life span when maintained in a specific pathogen-free environement (PubMed:17664292). However, they have increased mortality in association with late-onset failed bacterial clearance, and specifically increased neutrophil death (PubMed:17664292, PubMed:30692621). Mutant mice also show a severe defect in the bone marrow reserve of mature neutrophils demonstrating a key role for in cellular homeostasis (PubMed:21683252, PubMed:21248149). In addition, Serpinb1a-deficiency leads to maladaptive beta-cell proliferation in insulin-resistant states (PubMed:26701651).|||Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis (PubMed:17664292, PubMed:21683252, PubMed:21248149, PubMed:30692621). Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection (PubMed:17664292). These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3. Acts also as a potent intracellular inhibitor of granzyme H (PubMed:12189154). During inflammation, limits the activity of inflammatory caspases CASP1 and CASP4 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621). In addition, promotes the proliferation of beta-cells when secreted (PubMed:26701651).|||Secreted|||Ubiquitous with higher expression in pancreas, spleen and bone marrow. http://togogenome.org/gene/10090:Cmas ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B4|||http://purl.uniprot.org/uniprot/Q99KK2 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CMP-NeuNAc synthase family.|||Catalyzes the activation of N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc), a substrate required for the addition of sialic acid. Has some activity toward NeuNAc, N-glycolylneuraminic acid (Neu5Gc) or 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN).|||Highly expressed in brain and heart, and at intermediate level muscle and liver.|||Homotetramer; the active enzyme is formed by a dimer of dimers.|||Inactive.|||Nucleus|||The BC2 (basic cluster 2) motif is necessary and sufficient for the nuclear localization and contains the catalytic active site. The localization in the nucleus is however not required for the enzyme activity. http://togogenome.org/gene/10090:Dock9 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLE0|||http://purl.uniprot.org/uniprot/A0A1D5RMM1|||http://purl.uniprot.org/uniprot/A0A5F8MPL9|||http://purl.uniprot.org/uniprot/E9QMR2|||http://purl.uniprot.org/uniprot/F8VPN7 ^@ Similarity ^@ Belongs to the DOCK family. http://togogenome.org/gene/10090:Vmn1r234 ^@ http://purl.uniprot.org/uniprot/Q8R298 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Galnt3 ^@ http://purl.uniprot.org/uniprot/P70419 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:8912633). Has activity toward HIV envelope glycoprotein gp120 (By similarity). Has activity towards EA2, MUC2 and MUC5 (PubMed:8912633). Probably glycosylates fibronectin in vivo (By similarity). Glycosylates FGF23 (By similarity).|||Golgi stack membrane|||Highly expressed in the reproductive tract, principally in the testis and uterus, and to a lesser degree in the cervix with only trace levels in the ovary. Also expressed at high level in sublingual gland, stomach and colon, with more moderate amounts present in the submandibular and parotid gland as well as the kidney.|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity (By similarity). Essential for glycosylation of FGF23 (By similarity).|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Bspry ^@ http://purl.uniprot.org/uniprot/Q80YW5 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:10978534, testis-specific. According to PubMed:16371431, broadly expressed.|||Cytoplasm|||Down-regulated by vitamin D.|||Expression starts at 19 dpc in brain.|||Interacts with YWHAZ/14-3-3 protein zeta (By similarity). Interacts with TRPV5 and TRPV6.|||May regulate epithelial calcium transport by inhibiting TRPV5 activity.|||Membrane http://togogenome.org/gene/10090:Cul5 ^@ http://purl.uniprot.org/uniprot/E9Q6Z0|||http://purl.uniprot.org/uniprot/G3X914|||http://purl.uniprot.org/uniprot/Q2M4H5|||http://purl.uniprot.org/uniprot/Q9D5V5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cullin family.|||Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL5, Elongin BC (ELOB and ELOC), RBX2 and a variable SOCS box domain-containing protein as substrate-specific recognition component. Component of the probable ECS(LRRC41) complex with the substrate recognition component LRRC41. Component of the probable ECS(SOCS1) complex with the substrate recognition component SOCS1. Component of the probable ECS(WSB1) complex with the substrate recognition subunit WSB1. Component of the probable ECS(SOCS3) complex with the substrate recognition component SOCS3. Component of the probable ECS(SPSB1) complex with the substrate recognition component SPSB1. Component of the probable ECS(SPSB2) complex with the substrate recognition component SPSB2. Component of the probable ECS(SPSB4) complex with the substrate recognition component SPSB4. Component of the probable ECS(RAB40C) complex with the substrate recognition subunit RAB40C. Component of the probable ECS(KLHDC1) complex with the substrate recognition component KLHDC1. May also form complexes containing CUL5, elongin BC complex (ELOB and ELOC), RBX1 and ELOA. May also form complexes containing CUL5, Elongin BC (ELOB and ELOC), RBX1 and VHL. Interacts with RNF7/RBX2, LRRC41, SOCS3, SPSB1, SPSB2, SPSB4 and RAB40C. Interacts with ASB1, ASB2, ASB6, ASB7 and ASB12. Interacts (when neddylated) with ARIH2; leading to activate the E3 ligase activity of ARIH1. Interacts with NOS2 in the presence of SPSB1 or SPSB2 or SPSB4. Interacts with ERCC6; the interaction is induced by DNA damaging agents or inhibitors of RNA polymerase II elongation. Interacts with ELOA (via the BC-box). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation. Component of the probable ECS(PCMTD1) complex with the substrate recognition subunit PCMTD1.|||Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:23806657). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. ECS(KLHDC1) complex is part of the DesCEND (destruction via C-end degrons) pathway and mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A. May form a cell surface vasopressin receptor (By similarity).|||Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN).|||Nucleus http://togogenome.org/gene/10090:Mup19 ^@ http://purl.uniprot.org/uniprot/A2CGB6|||http://purl.uniprot.org/uniprot/A9C496|||http://purl.uniprot.org/uniprot/P02762 ^@ Allergen|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in the urine of adult male mice but absent from that of females.|||Belongs to the calycin superfamily. Lipocalin family.|||Binds pheromones that are released from drying urine of males. These pheromones affect the sexual behavior of females.|||Causes an allergic reaction in human.|||Secreted|||There are about 15 group 1 MUP genes and their transcripts make up about 5% of male mouse liver RNA. http://togogenome.org/gene/10090:Chl1 ^@ http://purl.uniprot.org/uniprot/P70232 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.|||Cell membrane|||Cleavage by metalloprotease ADAM8 in the extracellular part generates 2 soluble forms (125 kDa and 165 kDa) in vitro and is inhibited by metalloprotease inhibitors. In brain extracts, these two soluble forms are also present and are dramatically reduced in mice lacking ADAM8 (PubMed:14761956). Cleaved by BACE1 (PubMed:29325091).|||Expressed in the brain, in the cerebellum and in the spinal cord. Detected in the retina and the optic nerve. Expressed in neurons and glial cells in the central nervous system and by Schwann cells in the peripheral nervous system.|||Extracellular matrix and cell adhesion protein that plays a role in nervous system development and in synaptic plasticity. Both soluble and membranous forms promote neurite outgrowth of cerebellar and hippocampal neurons and suppress neuronal cell death. Plays a role in neuronal positioning of pyramidal neurons as well as in regulation of both the number of interneurons and the efficacy of GABAergic synapses. May play a role in regulating cell migration in nerve regeneration and cortical development. Potentiates integrin-dependent cell migration towards extracellular matrix proteins. Recruits ANK3 to the plasma membrane.|||May interact with L1CAM. May interact with ITGB1/ITGA1 heterodimer and ITGB1/ITGA2 heterodimer as well as with ANK3.|||Mice exhibit misguided axonal projections and aberrant axonal connectivity. They show alterations of hippocampal fiber organization and olfactory axon projections. Their exploratory behavior in novel environments is altered suggesting deficits in information processing and in attention. They also display signs of decreased stress and are more sociable and less aggressive. Heterozygous mice exhibit half levels of CHL1 expression in the hippocampus compared to their wild-type littermates, reflecting a gene dosage effect.|||N-glycosylated. Contains N-linked oligosaccharides with a sulfated carbohydrate structure type HNK-1 (SO4-3-GlcUABeta1,3GalBeta1,4GlcNAc).|||Not detectable in the forebrain at 11 dpc, weakly detectable at 13 dpc with highest detection at 18 dpc to postnatal day 7. Down-regulated at postnatal day 15 and further reduced in four-week-old animals.|||O-glycosylated.|||The DGEA motif seems to be a recognition site for integrin.|||The FIG[AQ]Y motif seems to be an ankyrin recruitment region.|||extracellular matrix http://togogenome.org/gene/10090:Mlst8 ^@ http://purl.uniprot.org/uniprot/A0A3Q4EC26|||http://purl.uniprot.org/uniprot/Q9DCJ1 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat LST8 family.|||Cytoplasm|||Death around 10.5 dpc due to multiple defects in vascular system development. In addition, they exhibit a delayed development of their cephalic region.|||Lysosome membrane|||Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Interacts directly with MTOR and RPTOR. Interacts with RHEB. Interacts with MEAK7. Interacts with SIK3.|||Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR. mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Within mTORC1, interacts directly with MTOR and RPTOR. Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity. Interacts with RHEB. Interacts with MEAK7. Interacts with SIK3. Interacts with SLC38A7; this interaction promotes the recruitment of mTORC1 to the lysosome and its subsequent activation.|||Phosphorylation at Thr-51 by CDK1 promotes ubiquitination by the SCF(FBXW7) complex, followed by degradation.|||Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals (PubMed:17141160). mTORC1 is activated in response to growth factors or amino acids (By similarity). In response to nutrients, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (By similarity). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy (By similarity). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (By similarity). Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity (By similarity). In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity (By similarity). mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (By similarity). mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (By similarity). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (By similarity). mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation (By similarity). mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422' (By similarity). mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657' (By similarity).|||Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1, which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1. mTORC2 also modulates the phosphorylation of PRKCA.|||Ubiquitination by the SCF(FBXW7) and SCF(FBXW11) complexes following phosphorylation at Thr-51 by CDK1, leads to its degradation by the proteasome. http://togogenome.org/gene/10090:Hmgb4 ^@ http://purl.uniprot.org/uniprot/Q6P8W9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HMGB family.|||Chromosome|||Expressed in adult germ cells (at protein level).|||Nucleus|||Strongly expressed in adult germ cells and weakly expressed embryonic gonads (PubMed:25609838). In meiotic germ cells, begins to accumulate during the leptotene stage, before its concentration increases further during the pachytene and diplotene stages, where it localizes to the sex body (PubMed:25609838). http://togogenome.org/gene/10090:Tex13a ^@ http://purl.uniprot.org/uniprot/A2AFS9 ^@ Similarity ^@ Belongs to the TEX13 family. http://togogenome.org/gene/10090:Dlg4 ^@ http://purl.uniprot.org/uniprot/Q62108 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAGUK family.|||Cell membrane|||Cytoplasm|||Highly expressed in CA1 stratum oriens and stratum radiatum hippocampal neurons (PubMed:26931375). Expressed in the outer plexiform layer of the retina of the eye (at protein level) (PubMed:28334377).|||Interacts through its PDZ domains with ANO2 and NETO1 (PubMed:19474308, PubMed:19243221). Interacts with KCNJ4 (By similarity). Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D (By similarity). Interacts with ERBB4 (By similarity). Interacts with KCNA1, KCNA2, KCNA3 and KCNA4 (By similarity). Interacts with SYNGAP1 (By similarity). Interacts with ASIC3 (By similarity). Interacts with CXADR (By similarity). Interacts with KCND2 (By similarity). Interacts with SEMA4C (PubMed:11134026). Interacts with LRRC4 and LRRC4B (PubMed:16980967). Interacts through its first PDZ domain with GRIK2 and CRIPT (By similarity). Interacts through its second PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON (By similarity). Interacts through its third PDZ domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3 (By similarity). Interacts through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN, SIPA1L1 and KIF13B (By similarity). Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK (By similarity). Interacts with ADR1B (PubMed:15358775). Interacts with ANKS1B and PRR7 (By similarity). May interact with HTR2A (PubMed:14988405). Interacts with ADAM22, KLHL17 and LGI1 (PubMed:20089912) (By similarity). Interacts with FRMPD4 (via C-terminus) (By similarity). Interacts with LRFN1, LRFN2 and LRFN4 (PubMed:16828986). Interacts (via N-terminal tandem pair of PDZ domains) with GPER1 (via C-terminus tail motif); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner (By similarity). Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-terminal domain) (By similarity). Interacts with SHANK3 (PubMed:24153177). Interacts with KCNJ4 (PubMed:11997254). Interacts with GPR85 (By similarity). Interacts with CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-module) (By similarity). Interacts with ADGRB1 (By similarity). Found in a complex with PRR7 and GRIN1 (By similarity). Interacts (via PDZ3 domain and to lesser degree via PDZ2 domain) with PRR7 (By similarity). Component of the postsynaptic hippocampal AMPA-type glutamate receptor (AMPAR) complex, at least composed of pore forming AMPAR subunits GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and SHISA7. Interacts (via its first two PDZ domains) with SHISA6 and SHISA7 (via PDZ-binding motif); the interaction is direct (PubMed:26931375, PubMed:29199957). Interacts (via PDZ domain 2) with SEMA4F (via PDZ-binding motif); this interaction may promote translocation of DLG4/SAP90 to the membrane (PubMed:11483650). Interacts with RPH3A and GRIN2A; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity). Interacts with ABR and BCR (By similarity). Interacts with DGKI (via PDZ-binding motif); controls the localization of DGKI to the synapse (By similarity). Interacts with C9orf72, SMCR8 and RAB39B (PubMed:31651360). Interacts with ZDHHC5 (PubMed:20178993). Interacts with PTEN (via PDZ domain-binding motif); the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity).|||Mice with a stop codon in the third PDZ domain have impaired spatial learning. NMDA-mediated synaptic plasticity is lost even though receptor levels and localization are unchanged. Long-term potentiation of synaptic transmission is enhanced due to minimal long-term depression.|||Palmitoylated. Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses. Palmitoylation by ZDHHC2 occurs when the synaptic activity decreases and induces DLG4 synaptic clustering. Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic density and function in synaptogenesis. Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering. Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2. Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during neuronal development which slow down in mature neurons.|||Postsynaptic density|||Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins (PubMed:15358775, PubMed:9853749). Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (Probable). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (By similarity).|||Presynapse|||Synapse|||The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to postsynaptic density.|||The PDZ domain 3 mediates interaction with ADR1B.|||Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.|||axon|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Gart ^@ http://purl.uniprot.org/uniprot/Q64737 ^@ Cofactor|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Binds 1 magnesium or manganese ion per subunit.|||Detected in liver, kidney and brain.|||Homodimer.|||In the C-terminal section; belongs to the GART family.|||In the N-terminal section; belongs to the GARS family.|||In the central section; belongs to the AIR synthase family.|||The C-terminal GART domain carries the phosphoribosylglycinamide formyltransferase activity.|||The N-terminal ATP-grasp domain carries the phosphoribosylamine--glycine ligase activity.|||The central AIRS domain carries the phosphoribosylformylglycinamidine cyclo-ligase activity.|||Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway. http://togogenome.org/gene/10090:Ubr3 ^@ http://purl.uniprot.org/uniprot/Q5U430|||http://purl.uniprot.org/uniprot/Q8CAW0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UBR1 family.|||E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:17462990). Does not bind to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (PubMed:17462990). May play a role in Shh signaling by mediating the ubiquitination of Kif7 (PubMed:27195754). May be important for MYH9 function in certain tissues, possibly by regulating the ubiquitination of MYH9 and consequently affecting its interaction with MYO7A (PubMed:27331610).|||Expressed in numerous cells of the smell, touch, vision, hearing and taste senses. Expressed in cells of the olfactory pathway, including the olfactory cell layer of the main olfactory epithelium (MOE), a mitral neuron cell layer of the olfactory bulb (OB), and a pyramidal cell layer of the piriform cortex of the olfactory cortex (OC). Expressed in the vomeronasal sensory epithelium of the vomeronasal organ (VNO) and the mitral cells of the accessory olfactory bulb. Expressed in tactile tissues, including the dorsal root ganglion, trigeminal ganglion and follicle-sinus complexes. Expressed in cells between hair follicle and sinus and also in the region of the rete ridge collar. Expressed in taste buds of the fungiform, circumvallate, and foliate papillae. Expressed in the spiral ganglion, the organ of Corti of the cochlea in the inner ear, in the sensory epithelium of macula and vestibular ganglion of the balancing system (at protein level). Expressed in the liver and skeletal muscle.|||Interacts with UBE2A and UBE2B.|||Knockout mice for Ubr3 in a B6-enriched background exhibited neonatal lethality associated with suckling impairment, but can be partially rescued if the litter size is reduced. Survived adult knockout mice for Ubr3 had female-specific behavioral anosmia (decreased sense of smell).|||Membrane|||Ubiquitin ligase protein which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. http://togogenome.org/gene/10090:Ninj2 ^@ http://purl.uniprot.org/uniprot/F8WIJ3|||http://purl.uniprot.org/uniprot/Q3TQA7|||http://purl.uniprot.org/uniprot/Q9JL89 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ninjurin family.|||By nerve injury; in Schwann cells.|||Composed of 4 alpha helices: 2 hydrophobic transmembrane regions (alpha3 and alpha4) and 2 alpha helices (alpha1 and alpha2). Alpha1 and alpha2 feature one hydrophobic side and a hydrophilic side. In normal conditions, NINJ2 is inactivated and alpha1 and alpha2 helices are not inserted into the membrane. Following NINJ2 activation, alpha1 and alpha2 helices insert into the membrane and drive NINJ2 oligomerization via interactions between alpha3 and alpha4 and the hydrophobic face of alpha1 from an adjacent subunit. Such structures disrupt membrane integrity and form a lesion through the introduction of the hydrophilic faces of alpha1 and alpha2 into the hydrophobic membrane.|||Effector of necroptotic and pyroptotic programmed cell death that mediates plasma membrane rupture (cytolysis). Acts downstream of Gasdermin (GSDMA, GSDMB, GSDMC, GSDMD, or GSDME) or MLKL during pyroptosis or necroptosis, respectively: oligomerizes in response to death stimuli and promotes plasma membrane rupture by introducing hydrophilic faces of 2 alpha helices into the hydrophobic membrane, leading to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (By similarity). Also acts as a homophilic transmembrane adhesion molecule involved in nerve regeneration. Promotes axonal growth (By similarity).|||In normal conditions, NINJ2 is inactivated. In response to death stimuli, homooligomerizes and disrupts membrane integrity by introducing the hydrophilic faces of alpha1 and alpha2 helices into the hydrophobic membrane.|||In the dorsal root ganglia, already detected at embryonic day 14, increasing until postnatal day 2 where the adult level is reached.|||Membrane http://togogenome.org/gene/10090:Sucnr1 ^@ http://purl.uniprot.org/uniprot/Q99MT6 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abolition of succinate-induced hypertension (PubMed:15141213). Mutants have less migration of Langerhans cells to draining lymph nodes and impaired tetanus toxoid-specific recall T cell responses (PubMed:18820681). Mutants show dimished immune responses to microbiota-derived succinate but respond normally to parasitic worm Nippostrongylus brasiliensis (PubMed:29735652). Conditional knockouts for adipose tissue show a higher body wight but have a total amount of white adipose tissue significantly lower than wild-types, whereas muscle mass is similar. They also have better glucose tolerance and insulin sensitivity. Upon high fat diet, mutants develop hepatic steatosis and glucose intolerance (PubMed:36977414). Myeloid conditional knockouts have adipose-tissue inflammation and glucose intolerance. They show an exacerbated diet-induced obesity (PubMed:27481132).|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expression in activated M1 macrophages is induced by LPS as well as IL1B.|||G protein-coupled receptor for succinate able to mediate signaling through Gq/GNAQ or Gi/GNAI second messengers depending on the cell type and the processes regulated (PubMed:15141213). Succinate-SUCNR1 signaling serves as a link between metabolic stress, inflammation and energy homeostasis (PubMed:27481132, PubMed:18820681, PubMed:30962591, PubMed:29735652). In macrophages, plays a range of immune-regulatory roles. During inflammation, succinate-SUCNR1 signaling may act as an anti-inflammatory mediator or boost inflammation depending on the inflammatory status of cells (PubMed:27481132, PubMed:30962591). Hyperpolarizes M2 macrophages versus M1 phenotype through Gq signaling by regulating the transcription of genes involoved in immune function (By similarity). In activated M1 macrophages, plays a pro-inflammatory role in response to LPS (PubMed:27481132). Expressed in dendritic cells, where it is involved in the sensing of immunological danger and enhances immunity. Mediates succinate triggered intracelleular calcium mobilization, induces migratory responses and acts in synergy with Toll-like receptor ligands for the production of proinflammatory cytokines as well as an enhancement of antigen-specific activation of helper T cells (PubMed:18820681). In the small intestine, mediates the activation of tuft cells by dietary succinate and triggers type 2 immunity (PubMed:29735652). In adipocytes, plays an important role in the control of energy metabolism. In response to succinate, controls leptin expression in an AMPK-JNK-CEBPA-dependent as well as circadian clock-regulated manner (PubMed:36977414). In muscle tissue, is expressed in non-muscle cells and coordinates muscle remodeling in response to the succinate produced during exercise training in a paracrine manner (PubMed:32946811). In retina, acts as a mediator of vessel growth during retinal development. In response to succinate, regulates the production of angiogenic factors, including VEGF, by retinal ganglion neurons (By similarity).|||Predominantly expressed in the kidney (proximal and distal tubules and the juxtaglomerular apparatus). Weakly expressed in liver, spleen and small intestine. Highly expressed in immature dendritic cells, expression rapidly downregulates after maturation. Also expressed in macrophages (PubMed:18820681, PubMed:27481132). Specifically expressed in intestinal tuft cells (PubMed:29735652). Expression in whole muscle is attributable to major non-myofibrillar resident cell types, including stromal, endothelial and satellite cell populations (PubMed:32946811). http://togogenome.org/gene/10090:Vmn1r115 ^@ http://purl.uniprot.org/uniprot/K7N6Y3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Neurod4 ^@ http://purl.uniprot.org/uniprot/O09105|||http://purl.uniprot.org/uniprot/Q545C0 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Expressed in retinal interneurons amacrine cells (at protein level). Expressed in neurons of ventricular zone of the retina at postnatal day 1 (P1). Expressed transiently in amacrine and horizontal cells of the inner nuclear layer (INL) of the retina at P7 until P14.|||Nucleus|||Probably acts as a transcriptional activator. Mediates neuronal differentiation. Required for the regulation of amacrine cell fate specification in the retina.|||Serine or threonine phosphorylation within the basic region may regulate neurogenic activity.|||Weakly expressed in the neural tube around 8.5 dpc. By 9.5 dpc, expression is prominent in the ventral brain and spinal cord, and weak expression begins in the retina. At 10.5 dpc, highly expressed in the trigeminal and dorsal root ganglions, and the ventral midbrain and hindbrain. At 12.5 dpc, expressed in the mantle layer of the brain and spinal cord, trigeminal ganglion, Rathke's pouch, dorsal root ganglion and the ventricular zone of the neural retina. At 16.5 dpc, expression becomes restricted to the anterior region, persisting in the diencephalon and neural retina but decreasing in other regions. http://togogenome.org/gene/10090:Sephs1 ^@ http://purl.uniprot.org/uniprot/Q6NZN9|||http://purl.uniprot.org/uniprot/Q6P1B6|||http://purl.uniprot.org/uniprot/Q8BH69 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the selenophosphate synthase 1 family. Class II subfamily.|||Binds 1 Mg(2+) ion per monomer.|||Cell membrane|||Homodimer.|||Nucleus membrane|||Synthesizes selenophosphate from selenide and ATP.|||The conserved active site Cys (or selenocysteine) residue in position 29 is replaced by a Thr. However, as function in selenoprotein synthesis is probable, it is possible Cys-31 is the active site. http://togogenome.org/gene/10090:Mapkapk3 ^@ http://purl.uniprot.org/uniprot/Q09HN3|||http://purl.uniprot.org/uniprot/Q3UMW7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4 (By similarity).|||No visible phenotype. Mice are fertile and do not exhibit behavioral phenotype. Mice do not show decreased production of inflammatory cytokines such as TNF and IL6 upon LPS-stimulation. Mice lacking both Mapkapk2 and Mapkapk3 show further reduction of TNF production, compared to mice lacking only Mapkapk2. These data suggest that Mapkapk3 may function additively in stress-induced cytokine production. MAPKAPK3 knockdown homozygous mice develop Bruch's membrane abnormal thickening and thinning progressing with age (PubMed:26744326).|||Nucleus|||Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1 (By similarity). Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313. Isoform 3 is degraded following phosphorylation at Thr-203.|||Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression.|||Ubiquitously expressed (at protein level). Isoform 3 is expressed in skeletal muscles and heart. http://togogenome.org/gene/10090:Cacna2d4 ^@ http://purl.uniprot.org/uniprot/F8VPL1|||http://purl.uniprot.org/uniprot/Q5RJF7 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calcium channel subunit alpha-2/delta family.|||Defects in Cacna2d4 are a cause of cone-rod dysfunction. Mice display affected retinal ribbon-type synapses. The retinopathy is accompanied by a substantial loss in the activities of the second-order neurons. Rod photoreceptor responses are maintained with reduced amplitude, whereas cone activities are absent.|||Dimer formed of alpha-2-2 and delta-2 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (Probable). Interacts with CACNA1C and CACNB3 (By similarity).|||May be proteolytically processed into subunits alpha-2-4 and delta-4 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role (By similarity).|||Membrane|||The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.|||The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. http://togogenome.org/gene/10090:Pigb ^@ http://purl.uniprot.org/uniprot/Q9JJQ0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 22 family. PIGB subfamily.|||Endoplasmic reticulum membrane|||Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the third alpha-1,2-mannose to Man2-GlcN-acyl-PI during GPI precursor assembly (By similarity). http://togogenome.org/gene/10090:Nherf2 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZX2|||http://purl.uniprot.org/uniprot/A0A0R4J006|||http://purl.uniprot.org/uniprot/Q9JHL1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Cell membrane|||Endomembrane system|||Homodimer, and heterodimer with NHERF1. Binds PDZK1. Interacts with SRY. Binds ADRB2, SLC9A3, P2RY1, P2YR2, RDX and LPAR2 (By similarity). Interacts with MCC (By similarity). Found in a complex with EZR, PODXL and NHERF2 (By similarity). Interacts (via the PDZ domains) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is detected in glomerular epithelium cells (By similarity). Interacts with SGK1 and KCNJ1/ROMK1 (By similarity). Interacts (via the PDZ domains) with SLC26A6 (By similarity).|||Nucleus|||Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression.|||Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May also act as scaffold protein in the nucleus (By similarity). http://togogenome.org/gene/10090:Krtap16-1 ^@ http://purl.uniprot.org/uniprot/A2A5X5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 16 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Klhl29 ^@ http://purl.uniprot.org/uniprot/Q80T74 ^@ Caution ^@ Although the complete sequence is not known with certainty, sequence shown here appears to be the most probable in accordance with human sequence ortholog. http://togogenome.org/gene/10090:Glb1 ^@ http://purl.uniprot.org/uniprot/P23780|||http://purl.uniprot.org/uniprot/Q3TAW7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 35 family.|||Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.|||Homodimer. May form higher multimers.|||Lysosome http://togogenome.org/gene/10090:Lif ^@ http://purl.uniprot.org/uniprot/F8WH42|||http://purl.uniprot.org/uniprot/P09056 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LIF/OSM family.|||LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.|||Secreted http://togogenome.org/gene/10090:Alg6 ^@ http://purl.uniprot.org/uniprot/Q3TAE8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man(9)GlcNAc(2)-PP-Dol (By similarity).|||Belongs to the ALG6/ALG8 glucosyltransferase family.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Nkrf ^@ http://purl.uniprot.org/uniprot/Q8BY02 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Enhances the ATPase activity of DHX15 by acting like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity of DHX15. Involved in the constitutive silencing of the interferon beta promoter, independently of the virus-induced signals, and in the inhibition of the basal and cytokine-induced iNOS promoter activity. Also involved in the regulation of IL-8 transcription. May also act as a DNA-binding transcription regulator: interacts with a specific negative regulatory element (NRE) 5'-AATTCCTCTGA-3' to mediate transcriptional repression of certain NK-kappa-B responsive genes.|||Interacts with NF-kappa-B. Interacts with XRN2. Interacts (via G-patch domain) with DHX15; promoting the RNA helicase activity of DHX15.|||nucleolus http://togogenome.org/gene/10090:Rassf3 ^@ http://purl.uniprot.org/uniprot/Q99P51 ^@ Subcellular Location Annotation ^@ Cytoplasm|||cytoskeleton http://togogenome.org/gene/10090:Or10s1 ^@ http://purl.uniprot.org/uniprot/Q8VGB3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Klrg1 ^@ http://purl.uniprot.org/uniprot/O88713 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By pathogens and viruses infections.|||Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. Upon phosphorylation of ITIM motif KLRG1 associates with the two phosphatases, PTPN11 and INPP5D.|||Expressed specifically on natural killer (NK) cells and activated CD8 T-cells. Not detected in spleen, thymus, lymph node, testis, brain or kidney. Not detected on mast cell lines, bone marrow-derived mast cells, or peritoneal mast cells.|||Forms a monomer and homodimer; disulfide-linked (By similarity). Interacts (via ITIM motif) with PTPN11 and INPP5D.|||Phosphorylated in response to monoclonal antibody G63 binding and antigenic stimulation.|||Plays an inhibitory role on natural killer (NK) cells and T-cell functions upon binding to their non-MHC ligands. May mediate missing self recognition by binding to a highly conserved site on classical cadherins, enabling it to monitor expression of E-cadherin/CDH1, N-cadherin/CDH2 and R-cadherin/CDH4 on target cells. http://togogenome.org/gene/10090:Senp1 ^@ http://purl.uniprot.org/uniprot/M0QWX4|||http://purl.uniprot.org/uniprot/P59110 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C48 family.|||Cytoplasm|||Death between 13.5 dpc and 14.5 dpc due to abnormalities in fetal vessels.|||Expression starts at 9.5 dpc.|||Interacts with MTA1. Interacts with CCAR2 (via N-terminus).|||Nucleus|||Protease that catalyzes two essential functions in the SUMO pathway (PubMed:15923632, PubMed:29499132). The first is the hydrolysis of an alpha-linked peptide bond at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3 leading to the mature form of the proteins. The second is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins, by cleaving an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein. Deconjugates SUMO1 from HIPK2 (By similarity). Deconjugates SUMO1 from HDAC1 and BHLHE40/DEC1, which decreases its transcriptional repression activity (By similarity). Deconjugates SUMO1 from CLOCK, which decreases its transcriptional activation activity (By similarity). Deconjugates SUMO2 from MTA1 (By similarity). Deconjugates SUMO2 from MTA1 (By similarity). Deconjugates SUMO1 from METTL3 (By similarity). Desumoylates CCAR2 which decreases its interaction with SIRT1 (By similarity). Deconjugates SUMO1 from GPS2 (PubMed:29499132). http://togogenome.org/gene/10090:Nfkbid ^@ http://purl.uniprot.org/uniprot/Q2TB02 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NF-kappa-B inhibitor family.|||Interacts with NFKB1, RELA and RELB; in the nucleus.|||Mice are highly sensitive to LPS-induced endotoxin shock and susceptible to intestinal inflammation caused by exposure to microflora. They display no overt T-cell selection phenotype but an impaired proliferation of T-cells. Thymocytes and T-cells seem to produce less IL-2 and IFNG.|||Nucleus|||Regulates the expression of IL-2, IL-6, and other cytokines through regulation on NF-kappa-B activity. Functions in the regulation of inflammatory responses (PubMed:11931770, PubMed:15749903, PubMed:16410444, PubMed:16413922, PubMed:17641034). Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR) (PubMed:25282160). According to PubMed:11931770, it may also regulate TCR-induced negative selection of thymocytes (PubMed:11931770).|||Specifically expressed in spleen and at low levels in thymus. Expressed in a population of antigen-presenting dendritic cells which may act as regulators of systemic inflammatory response.|||Up-regulated in thymocytes upon TCR-triggered cell death (at protein level). Up-regulated by IL-10 or LPS. http://togogenome.org/gene/10090:Ep300 ^@ http://purl.uniprot.org/uniprot/B2RWS6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylated on Lys at up to 17 positions by intermolecular autocatalysis. Deacetylated in the transcriptional repression domain (CRD1) by SIRT1, preferentially at Lys-1019. Deacetylated by SIRT2, preferentially at Lys-419, Lys-424, Lys-1541, Lys-1545, Lys-1548, Lys-1698, Lys-1703 and Lys-1706.|||Citrullinated at Arg-2143 by PADI4, which impairs methylation by CARM1 and promotes interaction with NCOA2/GRIP1.|||Cytoplasm|||Functions as histone acetyltransferase and regulates transcription via chromatin remodeling (By similarity). Acetylates all four core histones in nucleosomes (By similarity). Histone acetylation gives an epigenetic tag for transcriptional activation (By similarity). Mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein (PubMed:18486321, PubMed:24216764). Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability (By similarity). Mediates acetylation of histone H3 at 'Lys-27' (H3K27ac) (By similarity). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1 or SIRT2 (PubMed:28883095, PubMed:28576496). Acetylates 'Lys-131' of ALX1 and acts as its coactivator (By similarity). Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (By similarity). Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis (By similarity). Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription (By similarity). Acetylates HDAC1 leading to its inactivation and modulation of transcription (By similarity). Acetylates 'Lys-247' of EGR2 (PubMed:28576496). Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2 (By similarity). Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium (By similarity). Promotes cardiac myocyte enlargement (By similarity). Can also mediate transcriptional repression (By similarity). Acetylates FOXO1 and enhances its transcriptional activity (By similarity). Acetylates BCL6 wich disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity (By similarity). Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter (By similarity). Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity (PubMed:14645221, PubMed:9512516). Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity (PubMed:20955178). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (By similarity). Acetylates MEF2D (By similarity). Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degradation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990). Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (PubMed:25200183). Acetylates PCK1 and promotes PCK1 anaplerotic activity (By similarity). Acetylates RXRA and RXRG (By similarity). Acetylates isoform M2 of PKM (PKM2), promoting its homodimerization and conversion into a protein kinase (By similarity). Acetylates RPTOR in response to leucine, leading to activation of the mTORC1 complex (By similarity). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation or propionylation, respectively (PubMed:27105113). Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low (By similarity). Also acts as a histone butyryltransferase; butyrylation marks active promoters (PubMed:27105113). Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription (By similarity). Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes. Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (By similarity).|||Methylated at Arg-581 and Arg-605 in the KIX domain by CARM1, which blocks association with CREB, inhibits CREB signaling and activates apoptotic response. Also methylated at Arg-2143 by CARM1, which impairs interaction with NCOA2/GRIP1 (By similarity).|||Nucleus|||Part of a complex composed of MSX3, CREBBP/CBP AND EP300/p300; the interaction with MSX3 decreases histone acetylation activity (PubMed:11115394). Interacts with HIF1A; the interaction is stimulated in response to hypoxia and inhibited by CITED2. Probably part of a complex with HIF1A and CREBBP. Interacts (via N-terminus) with TFAP2A (via N-terminus); the interaction requires CITED2 (By similarity). Interacts (via CH1 domain) with CITED2 (via C-terminus) (PubMed:10593900). Interacts with CITED1 (unphosphorylated form preferentially and via C-terminus) (PubMed:10722728). Interacts with ESR1; the interaction is estrogen-dependent and enhanced by CITED1 (By similarity). Interacts with HIPK2 (PubMed:16917507). Interacts with DTX1, EID1, ELF3, FEN1, LEF1, NCOA1, NCOA6, NR3C1, PCAF, PELP1, PRDM6, SP1, SP3, SPIB, SRY, TCF7L2, DDX5, DDX17, SATB1, SRCAP and TRERF1 (By similarity). Interacts with JMY, the complex activates p53/TP53 transcriptional activity. Interacts with TTC5/STRAP; the interaction facilitates the association between JMY and p300/EP300 cofactors. Interacts with p53/TP53; the interaction is facilitated by TTC5/STRAP. Forms a complex with TTC5/STRAP and HSF1; these interactions augment chromatin-bound HSF1 and p300/EP300 histone acetyltransferase activity (By similarity). Part of a complex containing CARM1 and NCOA2/GRIP1. Interacts with ING4 and this interaction may be indirect. Interacts with ING5. Interacts with the C-terminal region of CITED4. Non-sumoylated EP300 preferentially interacts with SENP3. Interacts with SS18L1/CREST. Interacts with ALX1 (via homeobox domain) (By similarity). Interacts with NEUROD1; the interaction is inhibited by NR0B2 (PubMed:9512516). Interacts with TCF3 (By similarity). Interacts (via CREB-binding domain) with MYOCD (via C-terminus) (PubMed:15601857). Interacts with ROCK2 and PPARG. Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes. Interacts with IRF1 and this interaction enhances acetylation of p53/TP53 and stimulation of its activity. Interacts with FOXO1; the interaction acetylates FOXO1 and enhances its transcriptional activity. Interacts with ALKBH4 and DDIT3/CHOP. Interacts with KLF15 (By similarity). Interacts with CEBPB and RORA (PubMed:18486321, PubMed:24216764). Interacts with NPAS2, BMAL1 and CLOCK. Interacts with SIRT2 isoform 1, isoform 2 and isoform 5. Interacts with MTA1. Interacts with HDAC4 and HDAC5 in the presence of TFAP2C. Interacts with TRIP4 (By similarity). Interacts with NPAS2 (PubMed:14645221). Directly interacts with ZBTB49; this interaction leads to synergistic transactivation of CDKN1A (By similarity). Interacts with NR4A3 (PubMed:12709428). Interacts with ZNF451 (By similarity). Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding (PubMed:24216764). Interacts with HSF1. Interacts with ZBTB48/TZAP. Interacts with STAT1; the interaction is enhanced upon IFN-gamma stimulation. Interacts with HNRNPU (via C-terminus); this interaction enhances DNA-binding of HNRNPU to nuclear scaffold/matrix attachment region (S/MAR) elements. Interacts with BCL11B. Interacts with SMAD4; negatively regulated by ZBTB7A. Interacts with DUX4 (via C-terminus). Interacts with NUPR1; this interaction enhances the effect of EP300 on PAX2 transcription factor activity. Interacts with RXRA; the interaction is decreased by 9-cis retinoic acid. NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (By similarity). Interacts with RB1 (PubMed:20940255). Interacts with DDX3X; this interaction may facilitate HNF4A acetylation. Interacts with SOX9. Interacts with ATF4; EP300/p300 stabilizes ATF4 and increases its transcriptional activity independently of its catalytic activity by preventing its ubiquitination (By similarity). Interacts with KAT5; promoting KAT5 autoacetylation (By similarity).|||Phosphorylation at Ser-89 by AMPK reduces interaction with nuclear receptors, such as PPARG (By similarity). Phosphorylated by HIPK2 in a RUNX1-dependent manner. This phosphorylation that activates EP300 happens when RUNX1 is associated with DNA and CBFB. Phosphorylated by ROCK2 and this enhances its activity (By similarity).|||Probable target of ubiquitination by FBXO3, leading to rapid proteasome-dependent degradation.|||Sumoylated; sumoylation in the transcriptional repression domain (CRD1) mediates transcriptional repression. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3 (By similarity).|||The CRD1 domain (cell cycle regulatory domain 1) mediates transcriptional repression of a subset of p300 responsive genes; it can be de-repressed by CDKN1A/p21WAF1 at least at some promoters. It conatins sumoylation and acetylation sites and the same lysine residues may be targeted for the respective modifications. It is proposed that deacetylation by SIRT1 allows sumoylation leading to suppressed activity (By similarity). http://togogenome.org/gene/10090:Jak3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0R7|||http://purl.uniprot.org/uniprot/Q62137 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated, leading to regulate its activity. IL2 promotes phosphorylation on tyrosine residues, including autophosphorylation on Tyr-781 (By similarity). Dephosphorylation of Tyr-976 and Tyr-977 by PTPN2 negatively regulates cytokine-mediated signaling (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.|||Cytoplasm|||Endomembrane system|||In contrast with the ubiquitous expression of the other JAKs, JAK3 is predominantly expressed in hematopoietic tissues.|||Interacts with STAM2 and MYO18A. Interacts with SHB (By similarity).|||Mice show a severe block in B-cell development at the pre-B stage in the bone marrow. Additionally, they possesses small thymuses revealing a defect in T-cell development. The distribution of developmental subsets is relatively normal, suggesting a block in the expansion of early T-cell progenitors. Peripheral T-cells are present at normal or increased numbers but are functionally incompetent.|||Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion.|||Possesses two phosphotransferase domains. The second one contains the catalytic domain, while the presence of a pseudokinase domain is required for suppression of basal activity of JAK3. http://togogenome.org/gene/10090:Vmn1r64 ^@ http://purl.uniprot.org/uniprot/Q8R2B8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pygb ^@ http://purl.uniprot.org/uniprot/Q8CI94 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Activity of phosphorylase is controlled both by allosteric means (through the non-covalent binding of metabolites) and by covalent modification. Thus AMP allosterically activates, whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit, phosphorylase B (By similarity).|||Belongs to the glycogen phosphorylase family.|||Glycogen phosphorylase that regulates glycogen mobilization. Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.|||Homodimer. Dimers associate into a tetramer to form the enzymatically active phosphorylase A (By similarity).|||Phosphorylation of Ser-15 converts phosphorylase B (unphosphorylated) to phosphorylase A. http://togogenome.org/gene/10090:Anks3 ^@ http://purl.uniprot.org/uniprot/Q9CZK6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Homooligomer (By similarity). Interacts (via SAM domain) with ANKS6 (via SAM domain) (PubMed:25671767, PubMed:26327442, PubMed:26188091). Interacts with BICC1 (PubMed:25671767). Interacts with NPHP1 (PubMed:25671767). Interacts with NEK8 (PubMed:25671767, PubMed:26188091). Interacts with HIF1AN (PubMed:25671767). Interacts with NEK7; this interaction alters the subcellular distribution of NEK7 by preventing its nuclear translocation (PubMed:26188091).|||Hydroxylated at Asn-96, most probably by HIF1AN.|||Kidney (at protein level).|||May be involved in vasopressin signaling in the kidney.|||Phosphorylations at Ser-5, Ser-225, Thr-318, Ser-319, Ser-366 and Ser-369 occur in a NEK7-dependent manner.|||Polyubiquitinated.|||The SAM domain mediates homooligomerization.|||cilium http://togogenome.org/gene/10090:Ephx3 ^@ http://purl.uniprot.org/uniprot/Q3V1F8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.|||Catalyzes the hydrolysis of epoxide-containing fatty acids. Active in vitro against epoxyeicosatrienoic acids (EETs) including 8,9-EET, 9,10-EET, 11,12-EET and 14,15-EET and leukotoxin.|||Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA).|||Microsome membrane|||No visible phenotype. Mice are born at the expected Mendelian rate. No defect in the metabolism of epoxygenated fatty acid epoxide.|||Predominantly expressed in skin, esophagus, lung and tongue and to a lesser extent in pancreas and eye. http://togogenome.org/gene/10090:Atl1 ^@ http://purl.uniprot.org/uniprot/Q8BH66 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Endoplasmic reticulum membrane|||GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis. May also regulate Golgi biogenesis. May regulate axonal development.|||Golgi apparatus membrane|||Monomer as apoprotein and in the GDP-bound form. Homodimer in the GTP-bound form. Homooligomer. Interacts (via N-terminal region) with MAP4K4 (via CNH regulatory domain). Interacts with SPAST; interaction is direct (By similarity). Interacts with REEP5, RTN3 and probably RTN4 (via the transmembrane region) (PubMed:19665976). Interacts with REEP1. Interacts with CPT1C. Interacts with ARL6IP1 (By similarity). Interacts with ZFYVE27 (PubMed:24668814).|||axon http://togogenome.org/gene/10090:Dmgdh ^@ http://purl.uniprot.org/uniprot/Q9DBT9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GcvT family.|||Binds 1 FAD covalently per monomer.|||Catalyzes the demethylation of N,N-dimethylglycine to sarcosine. Also has activity with sarcosine in vitro.|||Mitochondrion http://togogenome.org/gene/10090:Tmem25 ^@ http://purl.uniprot.org/uniprot/Q9DCF1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed throughout the brain with higher levels within the hippocampus.|||In neurons, modulates the degradation of NMDA receptor GRIN2B subunit. Plays a role in the regulation of neuronal excitability.|||Interacts with GRIN2B.|||Late endosome|||Lysosome|||Secreted http://togogenome.org/gene/10090:Arhgap36 ^@ http://purl.uniprot.org/uniprot/B1AUC7 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Spcs2 ^@ http://purl.uniprot.org/uniprot/Q9CYN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPCS2 family.|||Component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (By similarity). Enhances the enzymatic activity of SPC and facilitates the interactions between different components of the translocation site (By similarity).|||Component of the signal peptidase complex paralog A (SPC-A) composed of a catalytic subunit SEC11A and three accessory subunits SPCS1, SPCS2 and SPCS3. Component of the signal peptidase complex paralog C (SPC-C) composed of a catalytic subunit SEC11C and three accessory subunits SPCS1, SPCS2 and SPCS3. Within the complex, interacts with SEC11A or SEC11C and SPCS1. The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Pik3ip1 ^@ http://purl.uniprot.org/uniprot/Q7TMJ8 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Negative regulator of hepatic phosphatidylinositol 3-kinase (PI3K) activity. http://togogenome.org/gene/10090:Ppp1r1b ^@ http://purl.uniprot.org/uniprot/Q60829 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein phosphatase inhibitor 1 family.|||Cytoplasm|||Dopamine- and cyclic AMP-regulated neuronal phosphoprotein.|||Inhibitor of protein-phosphatase 1.|||Phosphorylation of Thr-34 is required for activity. http://togogenome.org/gene/10090:Cops4 ^@ http://purl.uniprot.org/uniprot/O88544|||http://purl.uniprot.org/uniprot/Q14AI7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CSN4 family.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 (By similarity). Also involved in the deneddylation of non-cullin subunits such as STON2 (By similarity). The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, possibly via its association with CK2 and PKD kinases (By similarity). CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively (By similarity).|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS1, COPS2, COPS3, COPS5, COPS6, COPS7 (COPS7A or COPS7B) and COPS8 (By similarity). Interacts with TOR1A; the interaction is direct and associates TOR1A and SNAPIN with the CSN complex (By similarity). Interacts with STON2; controls STON2 neddylation levels (By similarity). Interacts with ERCC6 (By similarity).|||Cytoplasm|||Nucleus|||Vesicle|||synaptic vesicle http://togogenome.org/gene/10090:Umps ^@ http://purl.uniprot.org/uniprot/P13439|||http://purl.uniprot.org/uniprot/Q544K9 ^@ Function|||Similarity|||Subunit ^@ Bifunctional enzyme catalyzing the last two steps of de novo pyrimidine biosynthesis, orotate phosphoribosyltransferase (OPRT), which converts orotate to orotidine-5'-monophosphate (OMP), and orotidine-5'-monophosphate decarboxylase (ODC), the terminal enzymatic reaction that decarboxylates OMP to uridine monophosphate (UMP).|||Homodimer; dimerization is required for enzymatic activity.|||In the C-terminal section; belongs to the OMP decarboxylase family.|||In the N-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family. http://togogenome.org/gene/10090:Jakmip2 ^@ http://purl.uniprot.org/uniprot/D3YXK0 ^@ Similarity ^@ Belongs to the JAKMIP family. http://togogenome.org/gene/10090:Vmn2r20 ^@ http://purl.uniprot.org/uniprot/L7N2B1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pet100 ^@ http://purl.uniprot.org/uniprot/P0DJE0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PET100 family.|||Interacts with COX7A2.|||Membrane|||Mitochondrion|||Mitochondrion inner membrane|||Plays a role in mitochondrial complex IV assembly. http://togogenome.org/gene/10090:Prdx6 ^@ http://purl.uniprot.org/uniprot/D3Z0Y2|||http://purl.uniprot.org/uniprot/O08709|||http://purl.uniprot.org/uniprot/Q6GT24 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxiredoxin family. Prx6 subfamily.|||Cytoplasm|||Highly expressed in heart, kidney and liver. Moderate expression in brain and stomach. Very low levels in intestine.|||Homodimer (By similarity). Interacts with GSTP1; mediates PRDX6 glutathionylation and regeneration (By similarity). Interacts with APEX1. Interacts with STH. May interact with FAM168B (By similarity). May interact with HTR2A (PubMed:14988405).|||Irreversibly inactivated by overoxidation of Cys-47 to sulfinic acid (Cys-SO(2)H) and sulfonic acid (Cys-SO(3)H) forms upon oxidative stress.|||Lysosome|||MJ33 or lithium;[(2R)-1-hexadecoxy-3-(2,2,2-trifluoroethoxy)propan-2-yl] methyl phosphate inhibits its phospholipase A2 activity (PubMed:26830860). CI-976 or 2,2-Dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide inhibits its lysophosphatidylcholine acyltransferase activity (PubMed:26830860).|||Phosphorylation at Thr-177 by MAP kinases increases the phospholipase activity of the enzyme (By similarity). The phosphorylated form exhibits a greater lysophosphatidylcholine acyltransferase activity compared to the non-phosphorylated form (By similarity).|||The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this 1-Cys peroxiredoxin, no C(R) is present and C(P) instead forms a disulfide with a cysteine from another protein or with a small thiol molecule. C(P) is reactivated by glutathionylation mediated by glutathione S-transferase Pi, followed by spontaneous reduction of the enzyme with glutathione.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (By similarity). Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides (By similarity). Has phospholipase activity (PubMed:26830860). Can either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity) (By similarity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH (By similarity). Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis (By similarity). Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:26830860). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (By similarity).|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. http://togogenome.org/gene/10090:Gal ^@ http://purl.uniprot.org/uniprot/A0A498WGR4|||http://purl.uniprot.org/uniprot/P47212|||http://purl.uniprot.org/uniprot/Q3V002 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the galanin family.|||Endocrine hormone of the central and peripheral nervous systems that binds and activates the G protein-coupled receptors GALR1, GALR2, and GALR3 (By similarity). This small neuropeptide may regulate diverse physiologic functions including contraction of smooth muscle of the gastrointestinal and genitourinary tract, growth hormone and insulin release and adrenal secretion (By similarity).|||Expressed in retinal progenitor cells and retinal ganglion cells (at protein level).|||Secreted http://togogenome.org/gene/10090:Gemin7 ^@ http://purl.uniprot.org/uniprot/Q9CWY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gemin-7 family.|||Cytoplasm|||Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (By similarity). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (By similarity). Interacts with GEMIN6; the interaction is direct (By similarity). Interacts with STRAP/UNRIP; the interaction is direct (By similarity). Interacts with GEMIN8; the interaction is direct (By similarity). Interacts with SNRPB, SNRPD2, SNRPD3 and SNRPE; the interaction is direct (By similarity).|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (By similarity).|||gem|||nucleoplasm http://togogenome.org/gene/10090:Taf1b ^@ http://purl.uniprot.org/uniprot/P97358 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds. The RRN7-type zinc finger plays an essential postrecruitment role in Pol I transcription at a step preceding synthesis of the first 40 nucleotides (By similarity).|||Belongs to the RRN7/TAF1B family.|||Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment events in polymerase I (Pol I) transcription. Binds rDNA promoters and plays a role in Pol I recruitment as a component of the SL1/TIF-IB complex and, possibly, directly through its interaction with RRN3.|||Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1C. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with TBP and RRN3. Interacts with FLNA (via N-terminus).|||nucleolus http://togogenome.org/gene/10090:Arhgap27 ^@ http://purl.uniprot.org/uniprot/A2AB59 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with SH3KBP1/CIN85.|||Membrane|||Rho GTPase-activating protein which may be involved in clathrin-mediated endocytosis. GTPase activators for the Rho-type GTPases act by converting them to an inactive GDP-bound state. Has activity toward CDC42 and RAC1 (By similarity).|||Widely expressed. Highly expressed in kidney, lung, small intestine and thymus. http://togogenome.org/gene/10090:Efnb1 ^@ http://purl.uniprot.org/uniprot/P52795|||http://purl.uniprot.org/uniprot/Q544L9 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Cell membrane|||Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development (PubMed:7929389, PubMed:10704386). Binding to Eph receptors residing on adjacent cells leads to contact-dependent bidirectional signaling into neighboring cells (PubMed:7929389, PubMed:10704386). Shows high affinity for the receptor tyrosine kinase EPHB1/ELK (By similarity). Can also bind EPHB2 and EPHB3 (PubMed:7929389). Binds to, and induces the collapse of, commissural axons/growth cones in vitro (PubMed:10704386). May play a role in constraining the orientation of longitudinally projecting axons (PubMed:10704386).|||Expressed in the floor plate throughout the period of commissural axon pathfinding (PubMed:10704386). In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912).|||Expressed on lateral floor plate cells, specifically on commissural axon segments that have passed through the floor plate. Expressed in cells of the retinal ganglion cell layer during retinal axon guidance to the optic disk (PubMed:10704386). Expressed in myogenic progenitor cells (PubMed:27446912).|||Inducible phosphorylation of tyrosine residues in the cytoplasmic domain.|||Interacts (via PDZ-binding motif) with GRIP1 and GRIP2 (via PDZ domain 6) (By similarity). Interacts with TLE1 (PubMed:21429299). The intracellular domain peptide interacts with ZHX2; the interaction enhances ZHX2 transcriptional repression activity (PubMed:19515908).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Membrane raft|||Nucleus|||Proteolytically processed. The ectodomain is cleaved, probably by a metalloprotease, to produce a membrane-tethered C-terminal fragment. This fragment is then further processed by the gamma-secretase complex to yield a soluble intracellular domain peptide which can translocate to the nucleus. The intracellular domain peptide is highly labile suggesting that it is targeted for degradation by the proteasome. http://togogenome.org/gene/10090:Tpst1 ^@ http://purl.uniprot.org/uniprot/O70281|||http://purl.uniprot.org/uniprot/Q4FK50 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein sulfotransferase family.|||Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.|||Golgi apparatus membrane|||Homodimer. Can also form heterodimers with TPST2.|||N-glycosylated.|||Ubiquitous. Detected in heart, brain, lung, liver, spleen, kidney, skeletal muscle and testis. http://togogenome.org/gene/10090:Frmd4a ^@ http://purl.uniprot.org/uniprot/Q8BIE6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts (via coiled-coil domain) with CYTH1 (via coiled-coil domain) (PubMed:20080746). Interacts with PARD3 (via coiled-coil domain) (PubMed:20080746). Found in a complex with PARD3, CYTH1 and FRMD4A (PubMed:20080746). Interacts with CYTH2 (PubMed:20080746). Interacts with CYTH3 (PubMed:20080746).|||Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (PubMed:20080746). Plays a redundant role with FRMD4B in epithelial polarization (PubMed:20080746). May regulate MAPT secretion by activating ARF6-signaling (By similarity).|||adherens junction|||cytoskeleton|||tight junction http://togogenome.org/gene/10090:Adora2a ^@ http://purl.uniprot.org/uniprot/Q60613|||http://purl.uniprot.org/uniprot/Q8CAU3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts (via cytoplasmic C-terminal domain) with USP4; the interaction is direct (By similarity). May interact with DRD4 (By similarity). Interacts with NECAB2 (By similarity). Interacts (via cytoplasmic C-terminal domain) with GAS2L2; interaction enhances receptor-mediated adenylyl cyclase activity (PubMed:23994616).|||Membrane|||Receptor for adenosine (By similarity). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity).|||Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.|||The cytoplasmic C-terminal domain is necessary for targeting the non-ubiquitinated form of this protein to the cell surface.|||Ubiquitinated. Deubiquitinated by USP4; leading to stabilization and expression at the cell surface (By similarity). http://togogenome.org/gene/10090:Xlr3a ^@ http://purl.uniprot.org/uniprot/Q60595|||http://purl.uniprot.org/uniprot/Q78PE0|||http://purl.uniprot.org/uniprot/Q99L59 ^@ Similarity|||Tissue Specificity ^@ Belongs to the XLR/SYCP3 family.|||Expressed in lymphoid cells. http://togogenome.org/gene/10090:Il3ra ^@ http://purl.uniprot.org/uniprot/P26952 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 5 subfamily.|||Cell membrane|||Cell surface receptor for IL3 expressed on hematopoietic progenitor cells, monocytes and B-lymphocytes that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells (By similarity). Ligand stimulation rapidly induces hetrodimerization with IL3RB, phosphorylation and enzyme activity of effector proteins such as JAK2 and PI3K that play a role in signaling cell proliferation and differentiation (PubMed:10477686, PubMed:31990690). Activation of JAK2 leads to STAT5-mediated transcriptional program (PubMed:10376805).|||Endomembrane system|||Interacts with IL3. Heterodimer of an alpha and a beta subunit (PubMed:10477686). The beta subunit is common to the IL3, IL5 and GM-CSF receptors.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||Ubiquitinated at Lys-357 by RNFT2 in response to IL3. Ubiquitination leads ligand-induced degradation by the proteasome. http://togogenome.org/gene/10090:Hsd3b3 ^@ http://purl.uniprot.org/uniprot/E9PXG7|||http://purl.uniprot.org/uniprot/P26150 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.|||Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Liver and kidney. Greater expression in liver.|||Mitochondrion membrane http://togogenome.org/gene/10090:Adamdec1 ^@ http://purl.uniprot.org/uniprot/Q3U0T4|||http://purl.uniprot.org/uniprot/Q9R0X2 ^@ Caution|||Cofactor|||Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Expressed highly in uterus during pregnancy.|||From the prepubertal period to day 5.5 of pregnancy is weakly expressed. From day 5.5 of pregnancy, an increase of expression is observed. At day 12.5 expression is higher.|||Induced by immunization in mature dendritic cells (DC), in marginal zone (MZ) metallophils, in follicular DC (FDC) and tingible body macrophages of germinal center. Down-regulated by steroid hormones and PRL.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play an important role in the control of the immune response and during pregnancy.|||Secreted http://togogenome.org/gene/10090:Rhox3f ^@ http://purl.uniprot.org/uniprot/A2ANE1|||http://purl.uniprot.org/uniprot/A6H657 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Fgd3 ^@ http://purl.uniprot.org/uniprot/Q3TNB8 ^@ Subcellular Location Annotation ^@ cytoskeleton http://togogenome.org/gene/10090:Fbp2 ^@ http://purl.uniprot.org/uniprot/P70695|||http://purl.uniprot.org/uniprot/Q3TKP4 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FBPase class 1 family.|||Binds 3 Mg(2+) ions per subunit.|||By retinoic acid.|||Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate.|||Cell junction|||Cytoplasm|||Expressed in muscle, intestine, brain and placenta and very weakly in liver.|||Homotetramer. Interacts with ALDOA; the interaction blocks inhibition by physiological concentrations of AMP and reduces inhibition by Ca(2+). Interacts with alpha-actinin and F-actin (By similarity).|||Nucleus|||Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. Fructose 2,6-bisphosphate acts as competitive inhibitor. Strongly inhibited by Ca(2+) (By similarity).|||Z line http://togogenome.org/gene/10090:Spn ^@ http://purl.uniprot.org/uniprot/P15702 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell surface of thymocytes, T-lymphocytes, neutrophils, plasma cells and myelomas.|||Cleavage by CTSG releases its extracellular domain and triggers its intramembrane proteolysis by gamma-secretase releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus.|||Has a high content of sialic acid and O-linked carbohydrate structures.|||Interacts with SIGLEC1.|||Interacts with isoform 2 of HIPK2 (PubMed:11078605). Interacts with CTNNB1 (By similarity). Interacts with RDX (via FERM domain) (PubMed:18614175). Interacts with EZR (PubMed:21289089). Interacts with MSN (By similarity) (PubMed:18614175, PubMed:21289089).|||Membrane|||Nucleus|||PML body|||Phosphorylation at Ser-347 is regulated by chemokines, requires its association with ERM proteins (EZR, RDX and MSN) and is essential for its function in the regulation of T-cell trafficking to lymph nodes.|||Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN) (PubMed:17638845, PubMed:21289089, PubMed:11728336). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment (PubMed:18490738). Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells. Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR (By similarity). Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin (PubMed:26700769). Acts as a T-cell counter-receptor for SIGLEC1 (PubMed:11238599).|||Protects cells from apoptotic signals, promoting cell survival.|||Sumoylated.|||microvillus|||uropodium http://togogenome.org/gene/10090:Tcf23 ^@ http://purl.uniprot.org/uniprot/Q9JLR5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both the bHLH region and the C-terminal portion are essential for inhibitory function.|||Forms inactive heterodimeric complex with TCF3.|||Highly expressed in the uterus (predominantly in myometrium), ovary, and testis. Expression in the uterus is higher in the diestrus phase than in the estrus phase and reaches a maximum at 7.5 dpc. Expression declines towards the time of delivery and returns to the non-pregnant level 4 days after delivery. Low expression seen in lung, heart, intestine, and spleen.|||Inhibits E-box-mediated binding and transactivation of bHLH factors. Inhibitory effect is similar to that of ID proteins. Inhibits the formation of TCF3 and MYOD1 homodimers and heterodimers. Lacks DNA binding activity. May be involved in the regulation or modulation of smooth muscle contraction of the uterus during pregnancy and particularly around the time of delivery. Seems to play a role in the inhibition of myogenesis.|||Nucleus http://togogenome.org/gene/10090:Ncaph2 ^@ http://purl.uniprot.org/uniprot/E9PY48|||http://purl.uniprot.org/uniprot/Q8BSP2 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CND2 H2 (condensin-2 subunit 2) family.|||Component of the condensin-2 complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits, NCAPG2, NCAPH2 and NCAPD3 that probably regulate the complex.|||Defects in Ncaph2 are the cause of the nessy phenotype which is characterized by a specific defect in T-cell development. Nessy thymuses are smaller, with corticomedullary junctions less well defined, and cortical cells sparser than in wild-type. The thymocyte defect is typified by an increased proportion of CD4-CD8- DN T-cell progenitors. Only thymocyte differentiation is affected in Nessy mice and not cell differentiation.|||Nucleus|||Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture (By similarity). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of chromatin bridges at anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). Seems to have lineage-specific role in T-cell development (By similarity). http://togogenome.org/gene/10090:Ephx4 ^@ http://purl.uniprot.org/uniprot/Q6IE26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.|||Membrane http://togogenome.org/gene/10090:Or5k1 ^@ http://purl.uniprot.org/uniprot/E9QAT7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zbtb20 ^@ http://purl.uniprot.org/uniprot/Q8K0L9 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can homodimerize. Binds to DNA.|||May be a transcription factor that may be involved in hematopoiesis, oncogenesis, and immune responses (By similarity). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (PubMed:27446912).|||Not expressed during development, is induced during establishment of satellite cells and acquisition of quiescence.|||Nucleus|||Specifically expressed in early hippocampal neurons, cerebellar granule cells and gliogenic progenitors as well as in differentiated glia (PubMed:11744704). Expressed in adult and aged myogenic satellite cells (PubMed:27446912).|||Sumoylated with SUMO1. http://togogenome.org/gene/10090:Esco1 ^@ http://purl.uniprot.org/uniprot/Q3UKT9|||http://purl.uniprot.org/uniprot/Q69Z69 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetyltransferase required for the establishment of sister chromatid cohesion. Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3.|||Belongs to the acetyltransferase family. ECO subfamily.|||Chromosome|||Nucleus|||Phosphorylated during mitosis.|||The N-terminal region seems to be responsible for association with chromosomes, thus excluding any involvement of the Zn finger in this process.|||The subunit structure is controversial. Monomer. Homodimer. http://togogenome.org/gene/10090:Fam241b ^@ http://purl.uniprot.org/uniprot/Q9D882 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM241 family.|||May play a role in lysosome homeostasis.|||Membrane http://togogenome.org/gene/10090:Asb12 ^@ http://purl.uniprot.org/uniprot/Q3KNI9|||http://purl.uniprot.org/uniprot/Q9D738 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Interacts with CUL5 and RNF7.|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Kat2a ^@ http://purl.uniprot.org/uniprot/Q6P3Z8|||http://purl.uniprot.org/uniprot/Q9JHD2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-542, inhibiting the protein acetyltransferase activity (By similarity). Deacetylation at Lys-542 by SIRT6 promotes phosphorylation at Ser-302 and Thr-728 and subsequent activation of the protein acetyltransferase activity, leading to acetylation and inactivation of PPARGC1A (By similarity).|||Belongs to the acetyltransferase family. GCN5 subfamily.|||Chromosome|||Expressed uniformly throughout the embryo from 7.5 to 9.0 dpc, except in the distal allantois and developing heart. Gcn5l2 expression is down-regulated after 16.5 dpc, but is later up-regulated in specific adult tissues.|||In brain, highly expressed in the hippocampal CA1 region (at protein level) (PubMed:25024434). Also expressed in the hippocampal subregions CA3 and the dentate gyrus as well as in the cortex and prefrontal cortex (PubMed:25024434). Expressed at low level in the cerebellum (PubMed:25024434).|||Interacts with EP300, CREBBP and ADA2 (By similarity). Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TAF3, TADA3L, SUPT3H/SPT3, TAF2/TAFII150, TAF4/TAFII135, TAF5/TAFII100, KAT2A/GCN5L2, TAF10 and TRRAP (By similarity). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, KAT2A, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (By similarity). The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22 (By similarity). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). In the complex, it probably interacts directly with KAT14, MBIP and WDR5 (By similarity). Interacts with PML (PubMed:22886304). Interacts with CEBPB (PubMed:17301242). Interacts with TACC1, TACC2 and TACC3 (By similarity). Interacts with RELA (PubMed:25024434). Interacts with NFATC2 (PubMed:28424240). Interacts with TBX5 (By similarity). Interacts with PLK4 (By similarity). Associates with the 2-oxoglutarate dehydrogenase complex (By similarity). Interacts with XPC; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (By similarity). Interacts with ERCC3/XPB; leading to KAT2A recruitment to promoters and subsequent acetylation of histones (By similarity). Interacts with ISL1. Interactions of ISL1 with MLIP1 or KAT2A may be mutually exclusive (PubMed:36112854).|||Lethality during embryogenesis: embryos develop normally to 7.5 days post coitum (dpc), but growth is severely retarded by 8.5 dpc and embryos fail to form dorsal mesoderm lineages, including chordamesoderm and paraxial mesoderm (PubMed:11017084). Differentiation of extra-embryonic and cardiac mesoderm is not affected (PubMed:11017084). Loss of the dorsal mesoderm lineages is due to an increased apoptosis (PubMed:11017084). Conditional knockout mice lacking Kat2a in the excitatory neurons of the adult forebrain display impaired hippocampus-dependent memory consolidation as well as impaired synaptic and nuclear plasticity (PubMed:25024434). Conditional knockout mice lacking Kat2a in T lymphocytes show defects in T-cell activation, T-cell proliferation, IL2 production and Th1/Th17 regulatory T-cell differentiation (PubMed:28424240). Th2 regulatory T-cell differentiation is not affected (PubMed:28424240).|||Loop3 is required for substrate specificity and adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Tyr-638 has an important role in the selective binding of succinyl-CoA over acetyl-CoA.|||Nucleus|||Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context (PubMed:28424240). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (By similarity). Succinylation of histones gives a specific tag for epigenetic transcription activation (By similarity). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (By similarity). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (By similarity). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (By similarity). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:28424240). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (By similarity). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (PubMed:25024434). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (PubMed:28424240). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (PubMed:30424580). Regulates embryonic stem cell (ESC) pluripotency and differentiation (PubMed:30270482). Also acetylates non-histone proteins, such as CEBPB, PPARGC1A, PLK4 and TBX5 (PubMed:17301242). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (By similarity). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (By similarity). Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A (By similarity). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (By similarity).|||centrosome http://togogenome.org/gene/10090:Cfap36 ^@ http://purl.uniprot.org/uniprot/Q8C6E0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CFAP36 family.|||Cytoplasm|||Interacts with ARL3.|||May act as an effector for ARL3.|||Nucleus|||flagellum http://togogenome.org/gene/10090:Mfn2 ^@ http://purl.uniprot.org/uniprot/Q80U63 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.|||Forms homomultimers and heteromultimers with MFN1 (PubMed:12527753). Oligomerization is essential for mitochondrion fusion (Probable). Interacts with VAT1 (By similarity). Interacts with STOML2; may form heterooligomers (By similarity). Interacts (phosphorylated) with PRKN (PubMed:23620051). Interacts with EIF2AK3 (By similarity). Interacts with THG1L; THG1L probably functions as a guanyl-nucleotide exchange factor/GEF, activating MFN2.|||Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12527753, PubMed:23921378, PubMed:23620051). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (By similarity). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes. Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (PubMed:23921556). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (PubMed:23921556).|||Mitochondrion outer membrane|||Mutant mice die early during embryonic development (PubMed:12527753). Heart-specific disruption causes cardiomyopathy in aging mice, characterized by dilated hearts that are insensitive to beta-adrenergic stimulation and impaired contractile performance (PubMed:23620051). Mutant cardiomyocytes display mitochondrial enlargement with respiratory impairment (PubMed:23620051).|||Phosphorylated by PINK1.|||Ubiquitinated by non-degradative ubiquitin by PRKN, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion (PubMed:23620051, PubMed:24513856). Ubiquitinated by HUWE1 when dietary stearate (C18:0) levels are low; ubiquitination inhibits mitochondrial fusion (By similarity).|||Ubiquitous. Expression is markedly reduced in ApoE-knockout mouse atherosclerotic arteries. http://togogenome.org/gene/10090:Mtm1 ^@ http://purl.uniprot.org/uniprot/B1AW21|||http://purl.uniprot.org/uniprot/Q3UDN6|||http://purl.uniprot.org/uniprot/Q9D4L1|||http://purl.uniprot.org/uniprot/Q9Z2C5 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by phosphatidylinositol 5-phosphate (PI5P).|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cell membrane|||Cytoplasm|||Expression increases during skeletal muscle cell differentiation.|||Heterodimer with MTMR12 (PubMed:23818870). Interacts with KMT2A/MLL1 (via SET domain) (By similarity). Interacts with DES in skeletal muscle but not in cardiac muscle (PubMed:21135508). Interacts with SPEG (By similarity).|||Late endosome|||Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine-containing peptides. Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome. Plays a role in vacuolar formation and morphology (By similarity). Regulates desmin intermediate filament assembly and architecture. Plays a role in mitochondrial morphology and positioning (PubMed:21135508). Required for skeletal muscle maintenance but not for myogenesis (PubMed:12391329). In skeletal muscles, stabilizes MTMR12 protein levels (PubMed:23818870).|||Mice are viable although lifespan is severely reduced. An under-representation of mutant males suggests some prenatal lethality. Generalized and progressive myopathy starts at around 4 weeks of age with amyotrophy and accumulation of central nuclei in skeletal muscle fibers, leading to death at 6-14 weeks. Mutants also show mitochondrial disorganization and increased levels of desmin with abnormal desmin intermediate filament formation and architecture.|||The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides.|||Widely expressed with highest levels detected in heart and muscle and low levels in brain (at protein level) (PubMed:12118066). Expressed in skeletal muscles (at protein level) (PubMed:23818870).|||filopodium|||ruffle|||sarcomere http://togogenome.org/gene/10090:Wdr19 ^@ http://purl.uniprot.org/uniprot/Q3UGF1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly (Probable). Essential for functional IFT-A assembly and ciliary entry of GPCRs (By similarity). Associates with the BBSome complex to mediate ciliary transport (PubMed:22922713).|||Component of the IFT complex A (IFT-A) complex. IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B (By similarity). Interacts (via C-terminal region) with IFT122 (via C-terminal region) (By similarity). Interacts with BBS1 (PubMed:22922713). Interacts with TTC25 (PubMed:25860617).|||Tissue-specific expression of isoforms (PubMed:12906858). Expressed in the prostate, testis, epididymis, submaxillary and salivary glands (PubMed:12906858). Expressed in ependymal cells lining brain ventricles (at protein level) (PubMed:16957054).|||cilium|||cilium basal body|||flagellum|||photoreceptor outer segment http://togogenome.org/gene/10090:Arxes2 ^@ http://purl.uniprot.org/uniprot/C0HK79|||http://purl.uniprot.org/uniprot/C0HK80 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Arxes1 and Arxes2 appear to have arisen by retrotransposition of the signal peptidase Spcs3 followed by a segmental duplication event.|||Belongs to the SPCS3 family.|||By the PPARG agonist rosiglitazone.|||Endoplasmic reticulum membrane|||Plays a role in adipogenesis.|||Strongly expressed in epididymal white and brown adipose tissue with low levels in heart.|||Strongly up-regulated during adipogenesis. http://togogenome.org/gene/10090:Cops9 ^@ http://purl.uniprot.org/uniprot/B2RVT1|||http://purl.uniprot.org/uniprot/Q3U898 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CSN9 family.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Plays a role in cell proliferation.|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9. In the complex, it interacts directly with COPS3, COPS5 and COPS6.|||Cytoplasm|||Nucleus|||The Phe/Asp-rich domain at the C-terminus is necessary for its incorporation into the CSN complex.|||nucleoplasm http://togogenome.org/gene/10090:Plpp5 ^@ http://purl.uniprot.org/uniprot/Q3UMZ3|||http://purl.uniprot.org/uniprot/Q6P6K4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Cell membrane|||Magnesium-independent phospholipid phosphatase with broad substrate specificity. Preferentially catalyzes the conversion of diacylglycerol pyrophosphate into phosphatidate but can also act on phosphatidate and lysophosphatidate. Phospholipid phosphatases are involved in both the synthesis of lipids and the generation or degradation of lipid-signaling molecules.|||Magnesium-independent phospholipid phosphatase. Inhibited by N-ethylmaleimide.|||Membrane|||Mice lacking Plpp5 are viable and display no overt physical defect.|||Specifically expressed by antibody-secreting immune cells. http://togogenome.org/gene/10090:Tenm3 ^@ http://purl.uniprot.org/uniprot/B7ZNJ5|||http://purl.uniprot.org/uniprot/G3X907 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tenascin family. Teneurin subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Ddx47 ^@ http://purl.uniprot.org/uniprot/Q4VBG1|||http://purl.uniprot.org/uniprot/Q9CWX9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX47/RRP3 subfamily.|||Interacts with AGO1 and AGO2. Interacts with GABARAP. Interacts with NOL8; the interaction is RNA-dependent (By similarity).|||Involved in apoptosis. May have a role in rRNA processing and mRNA splicing. Associates with pre-rRNA precursors (By similarity).|||nucleolus http://togogenome.org/gene/10090:Fkbp10 ^@ http://purl.uniprot.org/uniprot/Q61576 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Endoplasmic reticulum lumen|||Expressed in 12-day-old mouse; no or barely detectable expression is found in adult tissues.|||Expressed in aorta, brain, heart, kidney, lung, spleen and testis (PubMed:7493967, PubMed:11071917). Not detected in liver (PubMed:7493967).|||Inhibited by both FK506 and rapamycin, but not by cyclosporin A.|||N-glycosylated.|||PPIases accelerate the folding of proteins during protein synthesis.|||Phosphorylated. http://togogenome.org/gene/10090:Creld1 ^@ http://purl.uniprot.org/uniprot/A8C1T7|||http://purl.uniprot.org/uniprot/Q91XD7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CRELD family.|||Expressed in myoblast C2C12 cells (at protein level).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Protein disulfide isomerase (By similarity). Promotes the localization of acetylcholine receptors (AChRs) to the plasma membrane (PubMed:30407909). http://togogenome.org/gene/10090:Zfp281 ^@ http://purl.uniprot.org/uniprot/Q99LI5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Embryos die between embryonic day 7.5 (E7.5) and E8.5, due to dysregulation of pluripotency and lineage specific markers in embryonic stem cells (ESCs). Embryos show abnormal embryonic body differentiation.|||Interacts with NANOG. Associates with the NuRD complex.|||Nucleus|||Transcription repressor that plays a role in regulation of embryonic stem cells (ESCs) differentiation. Required for ESCs differentiation and acts by mediating autorepression of NANOG in ESCs: binds to the NANOG promoter and promotes association of NANOG protein to its own promoter and recruits the NuRD complex, which deacetylates histones. Not required for establishement and maintenance of ESCs. Represses the transcription of a number of genes including GAST, ODC1 and VIM. Binds to the G-rich box in the enhancer region of these genes. http://togogenome.org/gene/10090:Cog2 ^@ http://purl.uniprot.org/uniprot/Q921L5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG2 family.|||Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.|||Golgi apparatus membrane|||Required for normal Golgi morphology and function. http://togogenome.org/gene/10090:Cnrip1 ^@ http://purl.uniprot.org/uniprot/Q5M8N0 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the CNRIP family.|||Highly expressed in brain. Also detected in heart, lung, intestine, kidney, testis, spleen, liver and muscle (at protein level).|||Interacts with the cannabinoid receptor CNR1 (via C-terminus). Does not interact with cannabinoid receptor CNR2 (By similarity).|||Suppresses cannabinoid receptor CNR1-mediated tonic inhibition of voltage-gated calcium channels. http://togogenome.org/gene/10090:Mbtd1 ^@ http://purl.uniprot.org/uniprot/Q6P5G3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromatin reader component of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR). MBTD1 specifically recognizes and binds monomethylated and dimethylated 'Lys-20' on histone H4 (H4K20me1 and H4K20me2, respectively). In the NuA4 complex, MBTD1 promotes recruitment of the complex to H4K20me marks by competing with TP53BP1 for binding to H4K20me. Following recruitment to H4K20me at DNA breaks, the NuA4 complex catalyzes acetylation of 'Lys-15' on histone H2A (H2AK15), blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks, thereby promoting homologous recombination (HR).|||Chromosome|||Monomer. Component of the NuA4 histone acetyltransferase complex. Interacts with EPC1; interaction is direct and promotes recruitment of MBTD1 into the NuA4 histone acetyltransferase complex.|||Nucleus http://togogenome.org/gene/10090:Zfp30 ^@ http://purl.uniprot.org/uniprot/Q60585 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Pex16 ^@ http://purl.uniprot.org/uniprot/Q91XC9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxin-16 family.|||Interacts with PEX19.|||Peroxisome membrane|||Required for peroxisome membrane biogenesis. May play a role in early stages of peroxisome assembly. Can recruit other peroxisomal proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from the endoplasmic reticulum (ER). May function as receptor for PEX3 (By similarity). http://togogenome.org/gene/10090:Git2 ^@ http://purl.uniprot.org/uniprot/Q9JLQ2 ^@ Function|||PTM|||Subunit|||Tissue Specificity ^@ Expressed in the brain (at protein level).|||GTPase-activating protein for ADP ribosylation factor family members, including ARF1.|||May form heterooligomers with GIT1 (By similarity). Directly interacts with protein Piccolo/PCLO (By similarity). Interacts with PPFIA1 and PPFIA2 (By similarity). Interacts with ARHGEF7 (By similarity). Identified in a complex with ARHGEF6 and BIN2 (By similarity). Interacts with PAK3 (By similarity). Interacts with PXN/paxillin (By similarity). Interacts with TGFB1I1 (PubMed:10330411). Forms a complex with EFNB1 and GRB4/NCK2 (PubMed:17310244).|||Tyrosine phosphorylated when coexpressed in cells with PTK2/FAK1 and SRC. http://togogenome.org/gene/10090:Ptpn23 ^@ http://purl.uniprot.org/uniprot/Q6PB44 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cytoplasm|||Cytoplasmic vesicle|||Endosome|||Interacts with GRAP2 and GRB2. Interacts with UBAP1 and CHMP4B (By similarity).|||Nucleus|||Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis (By similarity).|||cilium basal body http://togogenome.org/gene/10090:Serpina10 ^@ http://purl.uniprot.org/uniprot/Q8R121 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Detectable in liver, but not in heart, brain, spleen, lung, kidney, skeletal muscle or testes.|||Heparin acts as an important cofactor, producing 20 to 100-fold accelerations of SERPINA10 reactions with factor Xa and factor XIa.|||Inhibits activity of the coagulation protease factor Xa in the presence of PROZ, calcium and phospholipids. Also inhibits factor XIa in the absence of cofactors (By similarity).|||May be due to a competing acceptor splice site.|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Zcchc12 ^@ http://purl.uniprot.org/uniprot/Q9CZA5 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the ZCCHC12 family.|||In embryonic brains expression is restricted to the ventral region of the forebrain, including the septum, amygdala, caudal putamen, and in the basal-forebrain cholinergic neurons. In adults, expressed in the brain, and at low levels in the testis.|||Interacts with SMAD1 and CREB-binding protein (CBP). Forms a protein-DNA complex through its association with SMAD1.|||Transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression. http://togogenome.org/gene/10090:Akr1c12 ^@ http://purl.uniprot.org/uniprot/Q9JLI0 ^@ Similarity ^@ Belongs to the aldo/keto reductase family. http://togogenome.org/gene/10090:Or5ac22 ^@ http://purl.uniprot.org/uniprot/E9Q8M0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Egf ^@ http://purl.uniprot.org/uniprot/A0A0G2JDT8|||http://purl.uniprot.org/uniprot/A0A0G2JF92|||http://purl.uniprot.org/uniprot/P01132|||http://purl.uniprot.org/uniprot/Q3UWD7 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6 (By similarity).|||Interacts with EGFR and promotes EGFR dimerization. Interacts with RHBDF1; may retain EGF in the endoplasmic reticulum and regulates its degradation through the endoplasmic reticulum-associated degradation (ERAD). Interacts with RHBDF2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Rimbp3 ^@ http://purl.uniprot.org/uniprot/Q3V0F0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RIMBP family.|||Component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development (PubMed:19091768, PubMed:28003339). Important for male fertility (PubMed:19091768).|||Detected in testis from postnatal day 20 onwards (at protein level). In developing spermatozoa, weakly expressed in pachytene spermatocytes and round spermatids, and highly expressed in elongating spermatids (at protein level). Detected in residual bodies but not mature sperm (at protein level).|||Interacts with FASLG (By similarity). Interacts with LRGUK (via guanylate kinase-like domain) (PubMed:28003339). Interacts (via C-terminus) with HOOK1 (via coiled-coil region) (PubMed:19091768).|||Males are almost completely infertile, but otherwise have no visible phenotype. Sperm morphology is highly abnormal with deformed nuclei, detached acrosomes and an expanded perinuclear space. Defects are first apparent from the round spermatid stage and are associated with abnormal development of the manchette.|||Specifically expressed in testis, where it localizes to postmeiotic germ cells (at protein level).|||cytoskeleton http://togogenome.org/gene/10090:Qki ^@ http://purl.uniprot.org/uniprot/Q9QYS9 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the quaking family.|||Cytoplasm|||Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (By similarity). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation (By similarity). Acts as a negative regulator of angiogenesis by binding to mRNAs encoding CDH5, NLGN1 and TNFAIP6, promoting their degradation (PubMed:32732889). Can also induce apoptosis in the cytoplasm (PubMed:11297509). Heterodimerization with other isoforms results in nuclear translocation of isoform QKI7 and suppression of apoptosis (PubMed:11297509). Also binds some microRNAs: promotes stabilitation of miR-122 by mediating recruitment of poly(A) RNA polymerase TENT2, leading to 3' adenylation and stabilization of miR-122 (By similarity).|||Cytosolic isoform that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (By similarity). Interaction with G3BP1 promotes localization of m7G-containing mRNAs into stress granules in response to stress, thereby suppressing their translation (By similarity). Acts as a translational repressor for HNRNPA1 and GLI1 (PubMed:10535969, PubMed:16198329, PubMed:20956316, PubMed:29021242). Translation inhibition of HNRNPA1 during oligodendrocyte differentiation prevents inclusion of exon 12 in MAG pre-mRNA splicing (PubMed:20956316). Involved in astrocyte differentiation by regulating translation of target mRNAs (PubMed:33750804).|||Defects in Qki are the cause of quakingviable (qkv). Qkv is a spontaneous mutation resulting in hypomyelinization of the central and peripheral nervous systems. Mutant mice develop normally until postnatal day 10 when they display rapid tremors or 'quaking' that is especially pronounced in hindlimbs and experience convulsive tonic-clonic seizures as they mature (PubMed:8589716). Mice with qkv specifically lack isoform 3 and isoform 4 in myelin-forming cells, while isoform 1 is lacking in oligodendrocytes of severely affected tracts (PubMed:12888522). Mice with qkv also lack the PRKN gene product, suggesting that the absence of PRKN may also affect the phenotype (PubMed:15014970).|||Embryonic lethality between 9.5 and 10.5 days post coitum (dpc) (PubMed:14706070). Embryos show a lack of large vitelline vessels in the yolk sacs, kinky neural tubes, pericardial effusion, open neural tubes and incomplete embryonic turning (PubMed:14706070). Conditional deletion in cardiomyocytes in the adult heart induces dilation of the ventricles and a rapid decline in cardiac function, associated with severe disruption of sarcomere organization (PubMed:36627242). Conditional deletion in neural stem cells leads to hypomyelination in the central nervous system due to impaired cholesterol biosynthesis (PubMed:33942715). Conditional deletion in microglia induces an inflammation phenotype, characterized by increased proinflammatory cytokine release and defects in processing phagocytosed cargo, leading to impaired remyelination (PubMed:33378678). Conditional deletion in astrocytes leads to impaired astrocyte maturation (PubMed:33750804).|||Expressed in early embryos, while isoform QKI6 and isoform QKI7 are found in late development when myelination begins.|||Expressed in late development when myelination begins.|||Expressed in neural progenitors of the ventricular zone (vz) during CNS development, but that expression is down-regulated during neuronal differentiation (PubMed:9778149). By contrast, neural progenitors located in specific subdomains of the vz maintain expression as they differentiate and migrate away into the emerging nervous system (PubMed:9778149). These have characteristics consistent with the acquisition of a glial rather than neuronal fate (at protein level) First detected in the neuroepithelium of the head folds at 7.5 dpc (PubMed:9778149). Expression is strongly present ventrally in the nascent brain and neural tube of 8.5 dpc and 9.5 dpc and in the heart of 8.5 dpc (PubMed:9778149).|||Highly expressed in myelin-forming cells. Expressed in oligodendrocytes and astrocytes in the central nervous system as well as Schwann cells in the peripheral nervous system. Also expressed in the yolk sac endoderm, adjacent to the mesodermal site of developing blood islands, where the differentiation of blood and endothelial cells first occurs (at protein level). Expressed in brain, lung, heart and testis.|||Homodimer; does not require RNA to homodimerize (PubMed:10506177, PubMed:11297509, PubMed:9671495, PubMed:22982292). Able to heterodimerize with BICC1 (PubMed:9315629).|||Interacts with G3BP1; directing N(7)-methylguanine (m7G)-containing mRNAs to stress granules to suppress mRNA translation (By similarity). Interacts with TENT2; promoting stabilization of miR-122 (By similarity).|||Interacts with G3BP1; directing N(7)-methylguanine (m7G)-containing mRNAs to stress granules to suppress mRNA translation.|||Methylated by PRMT1.|||Nuclear isoform that acts as an indirect regulator of mRNA splicing (PubMed:11917126, PubMed:29021242). Regulates mRNA splicing of MAG pre-mRNA by inhibiting translation of HNRNPA1 mRNA, thereby preventing MAG exon 12 alternative splicing (PubMed:11917126, PubMed:21253564). Involved in oligodendrocyte differentiation by promoting stabilization of SIRT2 mRNA (PubMed:28188285). Acts as a negative regulator of the interferon response by binding to MAVS mRNA, downregulating its expression (By similarity). Also inhibits the interferon response by binding to fibrinectin FN1 pre-mRNA, repressing EDA exon inclusion in FN1 (By similarity). Delays macrophage differentiation by binding to CSF1R mRNA, promoting its degradation (By similarity). In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2, promoting SREBF2/SREBP2-dependent cholesterol biosynthesis (PubMed:33942715, PubMed:34021134). SREBF2/SREBP2-dependent cholesterol biosynthesis participates to myelinization and is required for eye lens transparency (PubMed:33942715, PubMed:34021134).|||Nucleus|||RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as pre-mRNA splicing, circular RNA (circRNA) formation, mRNA export, mRNA stability and/or translation (PubMed:10535969, PubMed:11297509, PubMed:11917126, PubMed:12467586, PubMed:15568022, PubMed:31868295, PubMed:36088389). Involved in various cellular processes, such as mRNA storage into stress granules, apoptosis, lipid deposition, interferon response, glial cell fate and development (PubMed:10535969, PubMed:11297509, PubMed:11917126, PubMed:12467586, PubMed:15568022, PubMed:31868295). Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence (PubMed:16041388). Acts as a mRNA modification reader that specifically recognizes and binds mRNA transcripts modified by internal N(7)-methylguanine (m7G) (By similarity). Promotes the formation of circular RNAs (circRNAs) during the epithelial to mesenchymal transition and in cardiomyocytes: acts by binding to sites flanking circRNA-forming exons (PubMed:37272356). CircRNAs are produced by back-splicing circularization of pre-mRNAs (PubMed:37272356). Plays a central role in myelinization via 3 distinct mechanisms (PubMed:10864952, PubMed:12467586, PubMed:11917126, PubMed:15568022, PubMed:20956316, PubMed:21253564). First, acts by protecting and promoting stability of target mRNAs such as MBP, SIRT2 and CDKN1B, which promotes oligodendrocyte differentiation (PubMed:10864952, PubMed:15568022, PubMed:28188285). Second, participates in mRNA transport by regulating the nuclear export of MBP mRNA (PubMed:12467586). Finally, indirectly regulates mRNA splicing of MAG pre-mRNA during oligodendrocyte differentiation by acting as a negative regulator of MAG exon 12 alternative splicing: acts by binding to HNRNPA1 mRNA splicing factor, preventing its translation (PubMed:11917126, PubMed:20956316, PubMed:21253564). Involved in microglia differentiation and remyelination by regulating microexon alternative splicing of the Rho GTPase pathway (PubMed:33378678, PubMed:33045062). Involved in macrophage differentiation: promotes monocyte differentiation by regulating pre-mRNA splicing in naive peripheral blood monocytes (PubMed:36088389). Acts as an important regulator of muscle development: required for the contractile function of cardiomyocytes by regulating alternative splicing of cardiomyocyte transcripts (PubMed:33397958, PubMed:36627242). Acts as a negative regulator of thermogenesis by decreasing stability, nuclear export and translation of mRNAs encoding PPARGC1A and UCP1 (PubMed:31868295). Also required for visceral endoderm function and blood vessel development (PubMed:11892011, PubMed:16470614). May also play a role in smooth muscle development (PubMed:14706070). In addition to its RNA-binding activity, also acts as a nuclear transcription coactivator for SREBF2/SREBP2 (PubMed:33942715, PubMed:34021134).|||Stress granule|||The KH domain and the Qua2 region are involved in RNA binding.|||Tyrosine phosphorylated at its C-terminus, probably by FYN. Phosphorylation leads to decreased mRNA-binding affinity, affecting transport and/or stabilization of MBP mRNA. The level of Tyr phosphorylation in the developing myelin is highest in the first postnatal week (P7). During the vigorous accumulation of MBP mRNA between P7 and P20, phosphorylation in the developing myelin drastically declines. By the end of the fourth postnatal week (P28), phosphorylation is reduced approximately 90%.|||Ubiquitinated by RNF6 in macrophages, leading to its degradation.|||cytosol http://togogenome.org/gene/10090:Cnot8 ^@ http://purl.uniprot.org/uniprot/Q9D8X5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAF1 family.|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8. In the complex interacts directly with CNOT1. Interacts with BTG1, BTG2 and TOB1 (By similarity). Interacts with BTG4 (PubMed:27065194).|||Cytoplasm|||Expressed in embryonic stem (ES) cells.|||Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT7. Catalytic component of the CCR4-NOT complex which is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression. Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity.|||Nucleus http://togogenome.org/gene/10090:Thada ^@ http://purl.uniprot.org/uniprot/A8C756 ^@ Function|||Sequence Caution|||Similarity ^@ Belongs to the THADA family.|||Intron retention.|||Together with methyltransferase FTSJ1, methylates the 2'-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs. http://togogenome.org/gene/10090:Fbxo30 ^@ http://purl.uniprot.org/uniprot/Q8BJL1 ^@ Function|||Induction|||PTM|||Subunit ^@ Auto-ubiquitinated.|||May be neddylated. Neddylation may be required for E3 ligase activity, since it was observed only after purification with o-phenanthroline (PubMed:24076600).|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with SKP1, CUL1 and RBX1/ROC1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Required for muscle atrophy following denervation.|||Up-regulated in denervated muscles (at protein level), with highest expression levels around 14 days following denervation. Negatively regulated by the bone morphogenetic protein (BMP) pathway. http://togogenome.org/gene/10090:Ak5 ^@ http://purl.uniprot.org/uniprot/Q920P5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adenylate kinase family.|||Brain specific.|||Cytoplasm|||Monomer. Interacts with YWHAZ (PubMed:16959763).|||Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Active on AMP and dAMP with ATP as a donor. When GTP is used as phosphate donor, the enzyme phosphorylates AMP, CMP, and to a small extent dCMP. Also displays broad nucleoside diphosphate kinase activity. http://togogenome.org/gene/10090:Mrpl28 ^@ http://purl.uniprot.org/uniprot/Q9D1B9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL28 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Interacts with OXA1L.|||Mitochondrion http://togogenome.org/gene/10090:Bcl2a1c ^@ http://purl.uniprot.org/uniprot/Q0P538 ^@ Similarity ^@ Belongs to the Bcl-2 family. http://togogenome.org/gene/10090:Or8g28 ^@ http://purl.uniprot.org/uniprot/Q9EQB5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rrs1 ^@ http://purl.uniprot.org/uniprot/Q9CYH6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RRS1 family.|||Citrullinated by PADI4.|||Involved in ribosomal large subunit assembly. May regulate the localization of the 5S RNP/5S ribonucleoprotein particle to the nucleolus.|||nucleolus http://togogenome.org/gene/10090:Mthfs ^@ http://purl.uniprot.org/uniprot/Q9D110 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.|||Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-CHO-H(4)PteGlu) to yield 5,10-methenyltetrahydrofolate (By similarity).|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Naa16 ^@ http://purl.uniprot.org/uniprot/Q9DBB4 ^@ Function|||Subunit|||Tissue Specificity ^@ Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity.|||Component of the N-terminal acetyltransferase A (NatA) complex composed of NAA10 and NAA16.|||Highest levels in the kidney and testes. Moderate expression in the liver, thymus and skin. http://togogenome.org/gene/10090:H2az1 ^@ http://purl.uniprot.org/uniprot/P0C0S6|||http://purl.uniprot.org/uniprot/Q3UA95 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated on Lys-5, Lys-8, Lys-12 and Lys-14 by KAT2A; KAT2A is recruited by the XPC complex in absence of DNA damage (By similarity). Acetylated on Lys-5, Lys-8 and Lys-12 during interphase; acetylation disappears at mitosis (PubMed:16204459, PubMed:7217105). Acetylation by the NuA4 histone acetyltransferase complex is required for hematopoietic stem cell maintenance (PubMed:32542325).|||Belongs to the histone H2A family.|||Chromosome|||Down-regulation of H2az1 by RNA interference leads to death at early embryonic stages.|||Interacts (via M6 cassette) with ANP32E; leading to removal of H2A.Z/H2AZ1 from the nucleosome (By similarity). The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. H2A or its variant H2AZ1 forms a heterodimer with H2B (By similarity). Interacts with INCENP (PubMed:12660166). Interacts with VPS72 (via N-terminal domain); the interaction is enhanced by VPS72 phosphorylation which is promoted by ZNHIT1 (PubMed:30842416). Interacts with PWWP2A (By similarity). Interacts with FH (when phosphorylated by PRKDC) (By similarity). Interacts with ZNHIT1; the interaction results in recruitment of H2AZ1 to the MYOG promoter region which is required for muscle-specific gene expression (By similarity).|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated on Lys-5 and Lys-8 by SETD6. SETD6 predominantly methylates Lys-8, lys-5 being a possible secondary site.|||Monoubiquitination of Lys-122 gives a specific tag for epigenetic transcriptional repression.|||Not phosphorylated.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division. Essential for early development. http://togogenome.org/gene/10090:Shisa3 ^@ http://purl.uniprot.org/uniprot/Q3UPR0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ At 8.5 dpc, expressed in the foregut. At 9.5 dpc, expressed in the ventral mesencephalon and rhombencephalon. At 12.5 dpc, expressed in ventral midbrain, myotome and kidney.|||Belongs to the shisa family.|||Endoplasmic reticulum membrane|||Mutants exhibited no phenotype in either head development or somitogenesis.|||Plays an essential role in the maturation of presomitic mesoderm cells by individual attenuation of both FGF and WNT signaling. http://togogenome.org/gene/10090:Tbcc ^@ http://purl.uniprot.org/uniprot/A0A0R4J0M1|||http://purl.uniprot.org/uniprot/Q8VCN9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TBCC family.|||Cytoplasm|||Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state (By similarity).|||Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state.|||Tubulin-folding protein; involved in the final step of the tubulin folding pathway. http://togogenome.org/gene/10090:Apc ^@ http://purl.uniprot.org/uniprot/B2RUG9|||http://purl.uniprot.org/uniprot/Q8BNP7 ^@ Similarity ^@ Belongs to the adenomatous polyposis coli (APC) family. http://togogenome.org/gene/10090:Fbxl8 ^@ http://purl.uniprot.org/uniprot/Q8CIG9 ^@ Caution|||Function|||Subunit|||Tissue Specificity ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.|||While the gene symbol and protein names are indicative of the presence of LRR repeats, such repeats are not present in this protein.|||Widely expressed during embryogenesis and in adult tissues. http://togogenome.org/gene/10090:Trp53bp1 ^@ http://purl.uniprot.org/uniprot/A0A5H1ZRL7|||http://purl.uniprot.org/uniprot/P70399|||http://purl.uniprot.org/uniprot/Q3V1P7|||http://purl.uniprot.org/uniprot/Q8BZ87 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Asymmetrically dimethylated on Arg residues by PRMT1. Methylation is required for DNA binding.|||Chromosome|||Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:15159415, PubMed:15077110, PubMed:20453858, PubMed:23333305, PubMed:26308889, PubMed:20362325). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:23333305, PubMed:20362325, PubMed:30297459). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites. Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites. Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:15159415, PubMed:15077110). Participates in the repair and the orientation of the broken DNA ends during CSR (PubMed:26308889). In contrast, it is not required for classic NHEJ and V(D)J recombination (PubMed:15159415). Promotes NHEJ of dysfunctional telomeres (By similarity).|||Homoligomer (By similarity). Interacts with p53/TP53 (via the central domain) (By similarity). Interacts with DCLRE1C (By similarity). Interacts with histone H2AX and this requires phosphorylation of H2AX on 'Ser-139' (By similarity). Interacts with histone H4 that has been dimethylated at 'Lys-20' (H4K20me2) (PubMed:23209566). Has low affinity for histone H4 containing monomethylated 'Lys-20' (H4K20me1) (By similarity). Does not bind histone H4 containing unmethylated or trimethylated 'Lys-20' (H4K20me3) (By similarity). Has low affinity for histone H3 that has been dimethylated on 'Lys-79' (By similarity). Has very low affinity for histone H3 that has been monomethylated on 'Lys-79' (in vitro) (By similarity). Does not bind unmethylated histone H3 (By similarity). Interacts with histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) (By similarity). Interacts with PWWP3A/EXPAND1 (By similarity). Interacts with CHEK2; modulates CHEK2 phosphorylation at 'Thr-68' in response to infrared (By similarity). Interacts with MSL1; this interaction may be required for MSL1 DNA repair activity, but not for histone acetyltransferase activity (By similarity). Interacts (when phosphorylated by ATM) with RIF1 (PubMed:23333305, PubMed:23306439). Interacts (via the Tudor-like domain) with NUDT16L1/TIRR; interaction masks the Tudor-like domain and prevents recruitment to chromatin (By similarity). Interacts with PAXIP1 (By similarity). Interacts with IFI202A (PubMed:8910340). Interacts with SHLD2 (By similarity).|||Mice display growth retardation and are immune deficient, radiation-sensitive and cancer-prone (PubMed:12640136). Cells show a slight S-phase checkpoint defect and prolonged G2/M arrest after treatment with ionizing radiation (PubMed:12640136). Cells show defects in the DNA damage response (PubMed:12640136). Mice display defects in immunoglobulin class-switch recombination (CSR) during antibody genesis (PubMed:15159415, PubMed:15077110). In contrast, no defects are observed in classic NHEJ and V(D)J recombination (PubMed:15159415).|||Nucleus|||Phosphorylated at basal level in the absence of DNA damage (By similarity). Phosphorylated by ATM in response to DNA damage: phosphorylation at different sites promotes interaction with different set of proteins: phosphorylation at the N-terminus by ATM (residues from 11-181) promotes interaction with PAXIP1 and non-homologous end joining (NHEJ) of dysfunctional telomeres (By similarity). Phosphorylation by ATM at residues that are located more C-terminus (residues 300-650) leads to promote interaction with RIF1 (PubMed:23333305, PubMed:23306439). Interaction with RIF1 leads to disrupt interaction with NUDT16L1/TIRR (By similarity). Phosphorylation at Thr-1606 and Ser-1615 in the UDR motif blocks interaction with H2AK15ub (By similarity). Dephosphorylated by PPP4C (By similarity). Hyperphosphorylation during mitosis correlates with its exclusion from chromatin and DNA lesions (By similarity). Hyperphosphorylated in an ATR-dependent manner in response to DNA damage induced by UV irradiation (By similarity). Dephosphorylated by PPP5C (By similarity).|||The Tudor-like region mediates binding to histone H4 dimethylated at 'Lys-20' (H4K20me2) (PubMed:23209566). Interaction with NUDT16L1/TIRR masks the Tudor-like domain and prevents recruitment to chromatin (By similarity).|||The UDR (ubiquitin-dependent recruitment) motif specifically recognizes and binds histone H2A monoubiquitinated at 'Lys-15' (H2AK15ub). Phosphorylation of the UDR blocks interaction with H2AK15ub.|||kinetochore http://togogenome.org/gene/10090:Ccn1 ^@ http://purl.uniprot.org/uniprot/P18406|||http://purl.uniprot.org/uniprot/Q3TX21 ^@ Caution|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCN family.|||By growth factors.|||Expressed from G(0)/G(1) through mid-G(1) in normal cells, and at a constant level in rapidly growing cells.|||Interaction with integrins is heparin- and cell-type-dependent and promotes cell adhesion.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Low in kidney, adrenal gland, testes, brain, and ovary, moderate in heart, uterus, and skeletal muscle, highest in lung.|||Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5 (By similarity). CCN1-mediated gene regulation is dependent on heparin-binding (By similarity). Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1 (By similarity). Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-1/beta-5 and cell proliferation through integrin alpha-v/beta-3 (By similarity).|||Secreted http://togogenome.org/gene/10090:Psmd4 ^@ http://purl.uniprot.org/uniprot/O35226|||http://purl.uniprot.org/uniprot/Q3ULG4 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the proteasome subunit S5A family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD4 (PubMed:16857966). Interacts with NUB1. Interacts with SQSTM1. Interacts with UBQLN4. Interacts with UBE3A. Interacts with UBQLN1 (via ubiquitin-like domain). Interacts with DDI2 (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMD4 acts as an ubiquitin receptor subunit through ubiquitin-interacting motifs and selects ubiquitin-conjugates for destruction. Displays a preferred selectivity for longer polyubiquitin chains.|||Isoform Rpn10A is ubiquitous whereas isoform Rpn10E is mostly expressed in the embryonic brain.|||Isoform Rpn10E is expressed only in the embryos.|||The 2 UIM motifs are involved in the binding to a multi-ubiquitin chain in a cooperative way. http://togogenome.org/gene/10090:Mapk8 ^@ http://purl.uniprot.org/uniprot/A6P3E4|||http://purl.uniprot.org/uniprot/G3X8U9|||http://purl.uniprot.org/uniprot/Q544A0|||http://purl.uniprot.org/uniprot/Q7TSJ7|||http://purl.uniprot.org/uniprot/Q91Y86 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc, brain intermediate zone and cortical plate are significantly thicker in mutant mice compared to wild type. The number of neuronal cells is increased in the cortical plate and intermediate zone. Cell cycle exit is decreased by 13% in the ventricular and subventricular zones. In 17.5 dpc brains, the ventricular zone was thinner in mutant mice compared to wild type animals, consistent with the increased number of neurons in the cortical plate. TUBB3 is consistently more diffuse and less structured in mutant telencephalon than in wild type.|||At 15.5 dpc, mid to low expression throughout the midbrain, with more prominent levels in the telencephalon, especially in the intermediate zone, the midbrain roof, the olfactory epithelium, the inferior colliculus, and the medulla oblongata. telencephalon revealed concentrated (at protein level).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4 (PubMed:10523642, PubMed:12391307, PubMed:11562351). These proteins also bind other components of the JNK signaling pathway. Forms a complex with MAPK8IP1 and ARHGEF28 (PubMed:14499478). Interacts with TP53 and WWOX (By similarity). Interacts with JAMP (PubMed:16166642). Interacts with NFATC4 (By similarity). Interacts with MECOM; regulates JNK signaling (By similarity). Interacts with PIN1; this interaction mediates MAPK8 conformational changes leading to the binding of MAPK8 to its substrates (By similarity). Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs under both normal growth conditions and immediately upon heat shock (By similarity). Interacts (phosphorylated form) with NFE2; the interaction phosphorylates NFE2 in undifferentiated cells (PubMed:19966288). Interacts with GRIPAP1 (By similarity). Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-347' (PubMed:29153991). Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8IP1/JIP1 (PubMed:23963642). Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK9/JNK2 (PubMed:27084103).|||Brain (at protein level).|||Cytoplasm|||In T-cells, following T-cell receptor (TCR) activation. Levels peak 48 hours after TCR and CD-28 costimulation.|||Inhibited by SERPINB3 (By similarity). Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1.|||Nucleus|||Phosphorylated by TAOK2 (By similarity). Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme (PubMed:11562351). May be phosphorylated at Thr-183 and Tyr-185 by MAP3K1/MEKK1 (PubMed:17761173). Phosphorylated form is more concentrated at synapses than none-phosphorylated (By similarity).|||Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.|||Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:9393873, PubMed:28943315). Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:11602244). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins. Loss of this interaction abrogates the acetylation required for replication initiation. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:10811224). Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (By similarity). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:36812915). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (PubMed:21297631). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (PubMed:21297631). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (By similarity). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (PubMed:29153991). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (By similarity). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (By similarity). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315).|||Synapse|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. http://togogenome.org/gene/10090:Gdnf ^@ http://purl.uniprot.org/uniprot/P48540 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family. GDNF subfamily.|||Expressed in both the central nervous system (CNS) and in non-CNS tissues. Expressed in a highly dynamic pattern in the anterior neuroectoderm during the early stages of neurogenesis between 7.5 dpc and 10.5 dpc. Beginning at 10.5 dpc, expression begins in mesenchymal tissues of several organs including the digestive tract, kidney, testis, frontonasal mass, tooth primordium, tongue, mandible, whisker follicles, ear, eye, limb bud and in distinct regions of the brain. Also expressed in the heart, ileum, liver and muscle.|||Expression in C6 glioma cells was transiently induced by treatment with phorbol myristate acetate (PMA), but not by forskolin.|||First detected at 7.5 dpc, reaches its peak around 9.5 dpc and declines considerably after 10.5 dpc.|||Homodimer; disulfide-linked (By similarity). Interacts with RET (By similarity). Interacts (via propeptide) with SORL1 (via N-terminal ectodomain), either alone or in complex with GFRA1; interaction with SORL1 affects GDNF-regulated, but not constitutive secretion (PubMed:21994944). Also interacts with SORL1 in complex with GFRA1; this interaction leads to GDNF endocytosis and lysosomal degradation (By similarity).|||Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.|||Secreted http://togogenome.org/gene/10090:Gad2 ^@ http://purl.uniprot.org/uniprot/P48320|||http://purl.uniprot.org/uniprot/Q548L4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the group II decarboxylase family.|||Catalyzes the production of GABA.|||Cytoplasmic vesicle|||Golgi apparatus membrane|||Homodimer.|||Palmitoylated; which is required for presynaptic clustering.|||Phosphorylated; which does not affect kinetic parameters or subcellular location.|||Presynaptic cell membrane|||cytosol http://togogenome.org/gene/10090:Rfx5 ^@ http://purl.uniprot.org/uniprot/Q9JL61 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters.|||Belongs to the RFX family.|||Homodimer. The RFX heterotetrameric complex consists of 2 molecules of RFX5 and one each of RFXAP and RFX-B/RFXANK; with each subunit representing a separate complementation group (PubMed:10779326). Interacts (via PxLPxI/L motif) with RFXANK (via ankyrin repeats); the interaction is direct (By similarity). RFX forms cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX associates with CIITA to form an active transcriptional complex (PubMed:10779326).|||Nucleus|||Phosphorylated.|||The N-terminus is required for dimer formation, association with RFXANK and RFXAP, assembly of the RFX complex, and for binding of this complex to its X box target site in the MHC-II promoter. The C-terminus mediates cooperative binding between the RFX complex and NF-Y.|||The PxLPxI/L motif mediates interaction with ankyrin repeats of RFXANK. http://togogenome.org/gene/10090:Spin1 ^@ http://purl.uniprot.org/uniprot/Q3TLF7|||http://purl.uniprot.org/uniprot/Q61142 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPIN/STSY family.|||Chromatin reader that specifically recognizes and binds histone H3 both trimethylated at 'Lys-4' and asymmetrically dimethylated at 'Arg-8' (H3K4me3 and H3R8me2a) and acts as an activator of Wnt signaling pathway downstream of PRMT2. In case of cancer, promotes cell cancer proliferation via activation of the Wnt signaling pathway (By similarity). Overexpression induces metaphase arrest and chromosomal instability (PubMed:18543248). Localizes to active rDNA loci and promotes the expression of rRNA genes. May play a role in cell-cycle regulation during the transition from gamete to embryo. Involved in oocyte meiotic resumption, a process that takes place before ovulation to resume meiosis of oocytes blocked in prophase I: may act by regulating maternal transcripts to control meiotic resumption (PubMed:23894536).|||Early postnatal lethality. Ovarian folliculogenesis and oocyte growth appear normal but fully grown oocytes show defects in resuming meiosis.|||Gametogenesis. Synthesized from maternal transcripts but not from the zygote genome.|||Homodimer; may form higher-order oligomers. Interacts with TCF7L2/TCF4; the interaction is direct (By similarity). Interacts with HABP4 and SERBP1 (PubMed:23894536). Interacts with C11orf84/SPINDOC (By similarity).|||Nucleus|||Oocyte, egg, and very early embryo; not in the 8-, and 16-cell stage of the embryo. Isoform 1: Present in testis. Isoform 1 is more highly expressed in adult testes compared with newborn testes (at protein level).|||Phosphorylated during oocyte meiotic maturation.|||Post-translationally modified during the first mitotic cell cycle.|||The 3 tudor-like domains (also named Spin/Ssty repeats) specifically recognize and bind methylated histones. H3K4me3 and H3R8me2a are recognized by tudor-like domains 2 and 1, respectively.|||nucleolus|||spindle http://togogenome.org/gene/10090:Dpm3 ^@ http://purl.uniprot.org/uniprot/Q9D1Q4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DPM3 family.|||Component of the dolichol-phosphate mannose (DPM) synthase complex composed of DPM1, DPM2 and DPM3; within the complex, associates with DPM1 via its C-terminal domain and with DPM2 via its N-terminal portion. This interaction stabilizes DPM1 protein.|||Endoplasmic reticulum membrane|||Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit DPM1 to the endoplasmic reticulum. http://togogenome.org/gene/10090:Sec23a ^@ http://purl.uniprot.org/uniprot/Q01405|||http://purl.uniprot.org/uniprot/Q8C1E4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SEC23/SEC24 family. SEC23 subfamily.|||COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1 (By similarity). Interacts with SEC23IP (PubMed:10400679). Interacts with HTR4 (PubMed:15466885). Interacts with SEC16A (PubMed:17428803). Interacts with SLC6A4 (PubMed:17452640). Interacts (as part of the Sec23/24 complex) with SEC22B; recruits SEC22B into COPII-coated vesicles and allows the transport of this cargo from the endoplasmic reticulum to the Golgi. Interacts (via Gelsolin-like repeat) with MIA2 and MIA3; specifically involved in the transport of large cargos like the collagen COL7A1 (By similarity). Interacts with DDHD1 (PubMed:17428803). Interacts with TMEM39A (By similarity). Interacts with SACM1L; this interaction is reduced in the absence of TMEM39A (By similarity). Interacts with kinase FAM20C; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles (By similarity).|||COPII-coated vesicle membrane|||Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex (By similarity). Required for the translocation of insulin-induced glucose transporter SLC2A4/GLUT4 to the cell membrane (PubMed:27354378).|||Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules.|||Endoplasmic reticulum membrane|||High levels in brain and fibroblasts.|||Membrane|||The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs that include MIA2, MIA3 but also SEC31A. These interactions are probably competitive.|||cytosol http://togogenome.org/gene/10090:Cxcl17 ^@ http://purl.uniprot.org/uniprot/Q5UW37 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ All the mice injected with NIH3T3 cells over-expressing Cxcl17 develop rapidly progressing tumors within 21 days.|||Belongs to the intercrine alpha (chemokine CxC) family.|||Chemokine that acts as chemoattractant for monocytes, macrophages and dendritic cells (PubMed:24973458). Plays a role in angiogenesis and possibly in the development of tumors (PubMed:16989774). Acts as an anti-inflammatory in the stomach. May play a role in the innate defense against infections. Activates the C-X-C chemokine receptor GPR35 to induce a rapid and transient rise in the level of intracellular calcium ions.|||Detected in lung, trachea, lung, tongue thyroid, submaxillary gland, epididymis, and uterus tissues and at a lower level in ovary, prostate and in intestinal tissues.|||Likely to undergo an endoproteolytic process to form a four-cysteine-containing mature peptide with a canonical CXC chemokine scaffold after secretion.|||Mice show no defects in breeding or gross anatomy development, and they gained weight normally but exhibit a paucity of macrophages in the lungs (PubMed:24973458).|||Secreted http://togogenome.org/gene/10090:Fbxo34 ^@ http://purl.uniprot.org/uniprot/E9QM55|||http://purl.uniprot.org/uniprot/Q80XI1 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Zfp687 ^@ http://purl.uniprot.org/uniprot/Q9D2D7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Interacts with ZMYND8.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Cyp51 ^@ http://purl.uniprot.org/uniprot/Q8K0C4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Embryonic lethality at 15 dpc, likely due to heart failure. Mutant mice present complete block of de novo cholesterol synthesis at 14.5 dpc. Heart abnormalities include hypoplasia combined with ventricle septum and epicardial and vasculogenesis defects. Skeletal abnormalities include facial hypoplasia, brachycephaly, and bowed and jointed bones of the extremities with camptodactyly. Can serve as an animal model for studying Antley-Bixler syndrome.|||Endoplasmic reticulum membrane|||Inhibited by azalanstat. Inhibited by azole antifungal agents ketoconazole, itraconazole and fluconazole.|||Microsome membrane|||Sterol 14alpha-demethylase that plays a critical role in the cholesterol biosynthesis pathway, being cholesterol the major sterol component in mammalian membranes as well as a precursor for bile acid and steroid hormone synthesis (PubMed:21705796). Cytochrome P450 monooxygenase that catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of sterols such as lanosterol (lanosta-8,24-dien-3beta-ol) and 24,25-dihydrolanosterol (DHL) in the form of formate, and converts the sterols to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol and 4,4-dimethyl-8,14-cholestadien-3beta-ol, respectively, which are intermediates of cholesterol biosynthesis (PubMed:21705796). Can also demethylate substrates not intrinsic to mammals, such as eburicol (24-methylene-24,25-dihydrolanosterol), but at a lower rate than DHL (By similarity). http://togogenome.org/gene/10090:Nr0b1 ^@ http://purl.uniprot.org/uniprot/Q53ZY9|||http://purl.uniprot.org/uniprot/Q61066 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR0 subfamily.|||Cytoplasm|||Expressed at 5.5 dpc throughout the embryo except in the proximal visceral endoderm.|||Expressed in adult cerebral cortex, spinal cord, thymus, heart, lung, ovary, testis, adrenal gland, hypothalamus, spleen and kidney.|||Homodimer. Interacts with NR5A1, NR5A2, NR0B2 and with COPS2 (By similarity). Interacts with ESRRB; represses ESRRB activity at the GATA6 promoter (PubMed:27601327).|||Homodimerization involved an interaction between amino and carboxy termini involving LXXLL motifs and steroid binding domain (AF-2 motif). Heterodimerizes with NR5A1 and NROB2 through its N-terminal LXXLL motifs (By similarity).|||Nucleus|||Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity).|||Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency. http://togogenome.org/gene/10090:Khdc1a ^@ http://purl.uniprot.org/uniprot/Q3UWR2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the KHDC1 family.|||By NR4A1/NUR77.|||Cytoplasm|||Has pro-apoptotic activity. http://togogenome.org/gene/10090:Alg2 ^@ http://purl.uniprot.org/uniprot/Q9DBE8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.|||Mannosylates Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate.|||Membrane http://togogenome.org/gene/10090:Mmp27 ^@ http://purl.uniprot.org/uniprot/D3Z6I1 ^@ Cofactor|||Similarity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit. http://togogenome.org/gene/10090:Sly ^@ http://purl.uniprot.org/uniprot/A0A087WRK1|||http://purl.uniprot.org/uniprot/Q810R0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Nme7 ^@ http://purl.uniprot.org/uniprot/Q3UMG6|||http://purl.uniprot.org/uniprot/Q8BUH2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NDK family.|||cilium axoneme http://togogenome.org/gene/10090:Ndufb2 ^@ http://purl.uniprot.org/uniprot/Q9CPU2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB2 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or51a24 ^@ http://purl.uniprot.org/uniprot/Q7TRQ1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dennd4c ^@ http://purl.uniprot.org/uniprot/A6H8H2 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Cell membrane|||Cytoplasmic vesicle membrane|||Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin.|||Phosphorylated in response to insulin.|||cytosol http://togogenome.org/gene/10090:Tcl1b2 ^@ http://purl.uniprot.org/uniprot/P56841|||http://purl.uniprot.org/uniprot/Q4FZI4 ^@ Similarity ^@ Belongs to the TCL1 family. http://togogenome.org/gene/10090:Prl8a9 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0N6|||http://purl.uniprot.org/uniprot/Q9CQ58 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Detected only in placenta. Localized to spongiotrophoblasts and trophoblast giant cells of the placenta.|||First detected at 11.5 dpc and expressed continually throughout development, its expression level fluctuated during gestation.|||Secreted http://togogenome.org/gene/10090:Lsm2 ^@ http://purl.uniprot.org/uniprot/O35900|||http://purl.uniprot.org/uniprot/O35901|||http://purl.uniprot.org/uniprot/Q3U9X2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Binds specifically to the 3'-terminal U-tract of U6 snRNA.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA. http://togogenome.org/gene/10090:Spsb3 ^@ http://purl.uniprot.org/uniprot/D3YW96|||http://purl.uniprot.org/uniprot/Q571F5 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the SPSB family.|||Interacts with MET.|||May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Cxcl15 ^@ http://purl.uniprot.org/uniprot/Q9WVL7 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||By inflammation; in lung.|||Chemotactic for neutrophils. Involved in lung-specific neutrophil trafficking during normal and inflammatory conditions.|||Expression restricted to the lung, produced by bronchoepithelial cells and is released into the airways. Expressed at low levels in fetal lung.|||Mice develop normally and are fertile. They display normal leukocyte subpopulations in peripheral blood and bone marrow, but the amount of neutrophils is reduced in the airspace. Susceptibility to pneumonia induced by K.pneumoniae is increased with decreased survival and increased bacterial burden in lung.|||Secreted http://togogenome.org/gene/10090:Nop9 ^@ http://purl.uniprot.org/uniprot/Q8BMC4 ^@ Similarity ^@ Belongs to the NOP9 family. http://togogenome.org/gene/10090:Rdh16 ^@ http://purl.uniprot.org/uniprot/O54909 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum membrane|||Homodimer.|||Membrane topology is controversial (PubMed:16223484, PubMed:15355969). Membrane topology structure with endoplasmic reticulum lumen orientation of the catalytic domains while the C-terminus is in the cytosol have been suggested (PubMed:16223484, PubMed:11279029). Others investigators have argued for a reverse orientation, with a membrane-embedded N-terminal domain but no C-terminal transmembrane segment, and a cytosolic orientation of the catalytic domain (PubMed:15355969). These contradictory results are probably because of differences in the assay systems.|||Microsome membrane|||Not glycosylated.|||Oxidoreductase with a preference for NAD. Oxidizes all-trans-retinol, 9-cis-retinol, 11-cis-retinol and 13-cis-retinol to the corresponding aldehydes. Has higher activity towards CRBP-bound retinol than with free retinol. Oxidizes 3-alpha-hydroxysteroids. Oxidizes androstanediol and androsterone to dihydrotestosterone and androstanedione. Can also catalyze the reverse reaction.|||The C-terminal region plays a crucial role in controlling the activity of RDH16 and its required for endoplasmic reticulum (ER) retention. http://togogenome.org/gene/10090:Kcnk9 ^@ http://purl.uniprot.org/uniprot/Q3LS21 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Cell membrane|||Homodimer. Heterodimer with KCNK1.|||pH-dependent, voltage-insensitive, background potassium channel protein. http://togogenome.org/gene/10090:Cdkl3 ^@ http://purl.uniprot.org/uniprot/Q8BLF2 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||The [NKR]KIAxRE motif seems to be a cyclin-binding region. http://togogenome.org/gene/10090:Zfp365 ^@ http://purl.uniprot.org/uniprot/Q8BG89 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basket cells with reduced branches and short processes in the somatosensory cortex of adult knockout (KO) mice. Reduced expression of the gamma-aminobutyric acid-synthesizing enzymes Gad1 in the somatosensory cortex of KO mice (PubMed:23912123). Delayed myelination in the corpus callosum of KO mice during the postnatal period, but recovery by adulthood (PubMed:24481677). Decreased dendritic arborization and increased spine density dendrites in cortical pyramidal neurons of adult KO mice (PubMed:25983680).|||Contributes to genomic stability by preventing telomere dysfunction (PubMed:23776040). Involved in the morphogenesis of basket cells in the somatosensory cortex during embryogenesis (PubMed:23912123). Involved in the positive regulation of oligodendrocyte differentiation during postnatal growth (PubMed:24481677). Involved in dendritic arborization, morphogenesis of spine density dendrite, and establishment of postsynaptic dendrite density in cortical pyramidal neurons (PubMed:25983680). Involved in the regulation of neurogenesis. Negatively regulates neurite outgrowth. Involved in homologous recombination (HR) repair pathway. Required for proper resolution of DNA double-strand breaks (DSBs) by HR. Is required for recovery of stalled replication forks, and directly contributes to genomic stability. Interacts with PARP1 and mediates MRE11-dependent DNA end resection during replication fork recovery (By similarity).|||Detected in several tissues, with highest levels in brain. Also expressed during embryonic development. Expressed in cerebral cortex, hippocampus, striatum, inferior colliculus and thalamus (PubMed:23912123).|||Homodimer. Interacts with NDE1 and NDEL1 (By similarity). Interacts with DISC1. Interacts with PARP1 (By similarity).|||In the embryo at day 14.5 post-coitum, expressed in the basal, medial and lateral ganglionic eminences of the cerebral cortex, but not in the caudal ganglionic eminence (PubMed:23912123). Expressed in the corpus callosum from postnatal day 7 (PD7) to PD56 with a peak at PD14 (PubMed:24481677).|||Induced by gamma irradiation.|||centrosome http://togogenome.org/gene/10090:Tacr1 ^@ http://purl.uniprot.org/uniprot/P30548 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with ARRB1.|||This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin K. http://togogenome.org/gene/10090:Ldlr ^@ http://purl.uniprot.org/uniprot/A0A1L1SRE8|||http://purl.uniprot.org/uniprot/P35951 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LDLR family.|||Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.|||Cell membrane|||Early endosome|||Golgi apparatus|||Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (PubMed:11247302). Interacts (via NPXY motif) with LDLRAP1 (via PID domain) (By similarity). Interacts with ARRB1 (By similarity). Interacts with SNX17 (PubMed:12169628). Interacts with the full-length immature form of PCSK9 (via C-terminus) (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Late endosome|||Lysosome|||Membrane|||N- and O-glycosylated.|||The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.|||Ubiquitinated by MYLIP leading to degradation.|||clathrin-coated pit http://togogenome.org/gene/10090:Dph7 ^@ http://purl.uniprot.org/uniprot/Q9CYU6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DPH7 family.|||Catalyzes the demethylation of diphthine methyl ester to form diphthine, an intermediate diphthamide biosynthesis, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2).|||Interacts with INCA1. http://togogenome.org/gene/10090:Hexdc ^@ http://purl.uniprot.org/uniprot/Q3U4H6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 20 family.|||Cytoplasm|||Extracellular vesicle|||Has hexosaminidase activity (PubMed:19040401). Responsible for the cleavage of the monosaccharides N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) from cellular substrates. Has a preference for galactosaminide over glucosaminide substrates (By similarity).|||Homodimer; disulfide-linked.|||Inhibited by O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenylcarbamate (PUGNAc). Inhibited by galacto-NAG-thiazoline (By similarity).|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Trp73 ^@ http://purl.uniprot.org/uniprot/Q9D6A3|||http://purl.uniprot.org/uniprot/Q9JJP2|||http://purl.uniprot.org/uniprot/Z4YK94 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated and stabilized by interaction with RANBP9.|||Belongs to the p53 family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Found in a complex with p53/TP53 and CABLES1.|||Found in a complex with p53/TP53 and CABLES1. The C-terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2, HIPK2, RANBP9 and WWOX (By similarity). Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain) (By similarity). Interacts with YAP1 (phosphorylated form) (By similarity). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation (By similarity). Interacts (via SAM domain) with NQO1; this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome.|||Found in striatal neurons of mutant huntingtin (htt) transgenic mice (at protein level). Isoform 1 is expressed in the nasal epithelium, the vomeronasal organ, the hippocampus and the hypothalamus.|||Mice lacking Tp73 display a runting phenotype and high rates of mortality due to massive gastrointestinal hemorrhages or intracranial bleeding. The gastrointestinal tract suffers loss of enterocytes and excessive mucosecretions in the duodenum, ileum and cecum. Survivors exhibit hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways.|||Nucleus|||Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein.|||Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression, essential for the positive regulation of lung ciliated cell differentiation (PubMed:26947080).|||Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function (By similarity). Higher levels of phosphorylation seen in striatal neurons of. mutant huntingtin (htt) transgenic mice.|||Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome.|||Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 2.|||Sumoylated on Lys-622, which potentiates proteasomal degradation but does not affect transcriptional activity.|||The PPxY motif mediates interaction with WWOX. http://togogenome.org/gene/10090:Gm10061 ^@ http://purl.uniprot.org/uniprot/D3Z714 ^@ Function|||Subunit ^@ In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Ivns1abp ^@ http://purl.uniprot.org/uniprot/Q920Q8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Barely detected in the heart at 15.5 dpc, but clearly expressed in newborn heart with increased amount up to 8 weeks of age.|||Cytoplasm|||Decreased expression in various organs and cultured cell lines by doxorubicin treatment which may reduce mRNA stability.|||Disorganized actin skeleton is observed in cells transfected with isoform 2 (Nd1-S), which lacks the six kelch repeats.|||Homodimer; through the BTB domain. Interacts with AHR/Aryl hydrocarbon receptor (By similarity).|||Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats (PubMed:12213805, PubMed:16317045). Protects cells from cell death induced by actin destabilization (PubMed:16952015). Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription (By similarity). In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors (By similarity). Inhibits pre-mRNA splicing (in vitro) (By similarity).|||May play a role in cell cycle progression in the nucleus.|||Mice develop normally with no gross abnormalities. However, they display marked sensitivity to doxorubicin cardiotoxicity with increased number of cardiomyocytes apoptosis. Analysis of hearts from knockout mice reveal vacuolization and edema of cardiomaycytes.|||Nucleus|||Transgenic mice overexpressing Ivns1abp develop normally with no gross abnormalities up to 7-month old. However, they display a marked resistance to the cardiotoxic effect of doxorubicin which is an anti-neoplastic agent known to affect actin skeleton and an effective drug for cancer therapy with cardiotoxicity as side effect. Overexpression of Ivns1abp in the heart protect cardiomyocytes from apoptosis and improved survival rate after doxorubicin injection.|||Ubiquitous expression. In the heart, the highest expression is detected in the ventricles and the lowest in the atria. Expressed in dendrites and spines in neurons.|||When the BTB domain is lacking, AHR signaling induction promoted by IVNS1ABP is massively increased; Thus, the BTB domain inhibits AHR signaling induced by IVNS1ABP.|||cytoskeleton http://togogenome.org/gene/10090:Or51aa5 ^@ http://purl.uniprot.org/uniprot/K7N609 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Asb14 ^@ http://purl.uniprot.org/uniprot/E9QPD0|||http://purl.uniprot.org/uniprot/Q8C6Y6 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Stat3 ^@ http://purl.uniprot.org/uniprot/P42227|||http://purl.uniprot.org/uniprot/Q3ULI4|||http://purl.uniprot.org/uniprot/Q6GU23 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Phosphorylated on Tyr-705 in the presence of S.typhimurium SarA.|||Acetylated on lysine residues by CREBBP. Deacetylation by LOXL3 leads to disrupt STAT3 dimerization and inhibit STAT3 transcription activity. Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated.|||Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Tyrosine phosphorylated upon stimulation with EGF. Upon LPS challenge, phosphorylated within the nucleus by IRAK1 (By similarity). Upon UV-A treatment, phosphorylated on Ser-727 by RPS6KA5 (By similarity). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling (By similarity). Phosphorylation at Tyr-705 by PTK6, isoform M2 of PKM (PKM2) or FER leads to an increase of its transcriptional activity (By similarity).|||Belongs to the transcription factor STAT family.|||Cytoplasm|||Early embryonic lethality, day 6.5-7.5. Conditional, tissue specific mutants are variably viable and show diverse defects including obesity, diabetes, thermal dysregulation and infertility.|||Forms a homodimer or a heterodimer with a related family member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R in presence of IL23. Interacts (via SH2 domain) with NLK. Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 expression (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear import (By similarity). Interacts with CAV2; the interaction is increased on insulin-induced tyrosine phosphorylation of CAV2 and leads to STAT3 activation (By similarity). Interacts with ARL2BP; interaction is enhanced with ARL2. Interacts with NEK6 (By similarity). Binds to CDK9 when activated and nuclear. Interacts with BMX. Interacts with ZIPK/DAPK3. Interacts with PIAS3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. In prostate cancer cells, interacts with PRKCE and promotes DNA binding activity of STAT3. Interacts with STMN3, antagonizing its microtubule-destabilizing activity. Interacts with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts with FER. Interacts (via SH2 domain) with EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). Interacts with FGFR4 (By similarity). Interacts with INPP5F; the interaction is independent of STAT3 Tyr-705 phosphorylation status (By similarity). Interacts with OCAD1 (PubMed:23972987). Interacts (unphosphorylated or phosphorylated at Ser-727) with PHB1 (By similarity). Interacts and may form heterodimers with NHLH1 (PubMed:18356286). Found in a complex with SLC39A6, SLC39A10 and with the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (By similarity).|||Involved in the gp130-mediated signaling pathway.|||Nucleus|||STAT3A is seen in the liver, spleen, and kidney. STAT3B is also detected in the liver, although in a much less abundant manner. Expressed in the lung and an increase in expression levels seen during methicillin-resistant S.aureus infection.|||Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (By similarity). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (By similarity). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes (By similarity). Activated by IL31 through IL31RA (By similarity). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity (By similarity). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (By similarity). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (PubMed:12594516). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:16825198). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (By similarity). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (PubMed:20215569). Plays an important role in host defense in methicillin-resistant S.aureus lung infection by regulating the expression of the antimicrobial lectin REG3G (PubMed:23401489).|||Some lysine residues are oxidized to allysine by LOXL3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity. Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated. http://togogenome.org/gene/10090:Timm50 ^@ http://purl.uniprot.org/uniprot/Q9D880 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TIM50 family.|||Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50; within this complex, directly interacts with TIMM23. The complex interacts with the TIMM44 component of the PAM complex and with DNAJC15.|||Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Has some phosphatase activity in vitro; however such activity may not be relevant in vivo.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ldb3 ^@ http://purl.uniprot.org/uniprot/E9PYJ9|||http://purl.uniprot.org/uniprot/Q9JKS4 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed primarily in adult heart and skeletal muscle, and detected at lower levels in lung. Isoforms are expressed in a tissue-specific manner. Isoform 1, isoform 3 and isoform 5 are expressed in heart, whereas isoform 2, isoform 4 and isoform 6 are expressed in skeletal muscle.|||Initially expressed in a myocardium-specific manner at 8.5-9 dpc and remains cardiac-restricted until day 12. Strongly expressed throughout heart in all stages examined. At 12.5 dpc expressed at low levels in non-cardiac striated muscles. By 14.5 dpc expressed at high levels in both cardiac and skeletal muscle, and also strongly expressed in striated muscles of tongue, thoracic and abdominal muscles, leg and diaphragm. The various isoforms are developmentally regulated in both skeletal and cardiac muscle. Isoform 5 and isoform 6, which are barely detectable during embryogenesis are up-regulated postnatally. In heart, isoform 3 is up-regulated developmentally, whereas the predominant isoform 1 is expressed throughout development and into adulthood. In skeletal muscle, the predominant isoform 2 is gradually replaced by isoform 4 postnatally.|||Interacts via its LIM domains with various PKC isoforms. Interacts via its PDZ domain with the ACTN2 C-terminal region. Interacts with MYOZ1, MYOZ2 and MYOZ3.|||May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.|||Sequencing errors.|||Z line|||cytoskeleton|||perinuclear region|||pseudopodium http://togogenome.org/gene/10090:Mep1b ^@ http://purl.uniprot.org/uniprot/Q61847 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||By retinoic acid.|||Cell membrane|||Homotetramer consisting of disulfide-linked beta subunits, or heterotetramer of two alpha and two beta subunits formed by non-covalent association of two disulfide-linked heterodimers. Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity.|||Isoform 1 is expressed in kidney, intestinal brush borders, and salivary ducts. Isoform 2 has been found in carcinoma cells.|||Membrane metallopeptidase that sheds many membrane-bound proteins. Exhibits a strong preference for acidic amino acids at the P1' position (PubMed:11278902). Known substrates include: FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C. The presence of several pro-inflammatory cytokine among substrates implicate MEP1B in inflammation. It is also involved in tissue remodeling due to its capability to degrade extracellular matrix components (By similarity).|||N-glycosylated; contains high mannose and/or complex biantennary structures.|||Proteolytically activated by trypsin in the intestinal lumen and kallikrein-related peptidases in other tissues.|||Secreted|||Strongly inhibited by fetuin-A/AHSG (By similarity). Inhibited by cysteine and by the metal ion chelators EDTA and 1,10-phenanthroline. Not inhibited by 3,4-dichloroisocourmarin, soybean trypsin inhibitor, or the cysteine proteinase inhibitors iodoacetic acid and E-64. http://togogenome.org/gene/10090:Ghrl ^@ http://purl.uniprot.org/uniprot/A2RSS9|||http://purl.uniprot.org/uniprot/Q7TSD1|||http://purl.uniprot.org/uniprot/Q811T4|||http://purl.uniprot.org/uniprot/Q9EQX0 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Amidation of Leu-98 is essential for obestatin activity.|||Belongs to the motilin family.|||Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation.|||Levels of n-octanoylated and n-decanoylated ghrelin drop by one third and 3-fold, respectively, between postnatal weeks 3 and 4 due to change of diet during weaning.|||Mainly expressed in the gastrointestinal tract with higher levels in the stomach, medium levels in the duodenum, jejunum, ileum and colon. Low expression in the testis and brain. Not detected in the salivary gland, pancreas, liver and lung.|||O-octanoylated by GOAT/MBOAT4 (PubMed:18443287). O-octanoylation or O-decanoylation is essential for ghrelin activity (By similarity). The O-decanoylated form ghrelin-C10 differs in the length of the carbon backbone of the carboxylic acid bound to Ser-26 (PubMed:15746259).|||O-octanoylation is essential for ghrelin activity.|||Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility (By similarity).|||Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility.|||Secreted http://togogenome.org/gene/10090:Mmp10 ^@ http://purl.uniprot.org/uniprot/A1L3D0|||http://purl.uniprot.org/uniprot/O55123 ^@ Cofactor|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||By wounding.|||Can bind about 5 Ca(2+) ions per subunit.|||Can degrade fibronectin, gelatins of type I, III, IV, and V; weakly collagens III, IV, and V. Activates procollagenase.|||Expressed in small intestine. Weak levels in heart and lung.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix http://togogenome.org/gene/10090:Gdap1 ^@ http://purl.uniprot.org/uniprot/O88741 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily.|||Cytoplasm|||Expressed in brain, spinal cord, muscles and intestinal villi. In the central nervous system expressed most prominently in the cortex, cerebellum, thalamus, olfactory bulb, and spinal cord. Expressed also in sciatic nerves and in dorsal root ganglia.|||First expressed at embryonic stage 13 dpc. Levels then increase gradually to reach maximum levels at adulthood.|||Homodimer.|||Increased expression during neural differentiation.|||Mitochondrion outer membrane|||Regulates the mitochondrial network by promoting mitochondrial fission.|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.|||While belonging to the GST superfamily, it lacks glutathione transferase activity. http://togogenome.org/gene/10090:Or6p1 ^@ http://purl.uniprot.org/uniprot/E9Q5P8|||http://purl.uniprot.org/uniprot/Q8VG29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Polg2 ^@ http://purl.uniprot.org/uniprot/Q3V3E7|||http://purl.uniprot.org/uniprot/Q9QZM2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Heterotrimer composed of a catalytic subunit and a homodimer of accessory subunits.|||Mitochondrial polymerase processivity subunit. It regulates the polymerase and exonuclease activities promoting processive DNA synthesis. Binds to ss-DNA.|||Mitochondrion http://togogenome.org/gene/10090:Mcpt8 ^@ http://purl.uniprot.org/uniprot/P43430 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytoplasmic granule|||Secreted http://togogenome.org/gene/10090:Ccdc160 ^@ http://purl.uniprot.org/uniprot/Q3UYG1 ^@ Similarity ^@ Belongs to the CCDC160 family. http://togogenome.org/gene/10090:Tex2 ^@ http://purl.uniprot.org/uniprot/Q6ZPJ0 ^@ Domain|||Function|||Subcellular Location Annotation ^@ During endoplasmic reticulum (ER) stress or when cellular ceramide levels increase, may induce contacts between the ER and medial-Golgi complex to facilitate non-vesicular transport of ceramides from the ER to the Golgi complex where they are converted to complex sphingolipids, preventing toxic ceramide accumulation.|||Endoplasmic reticulum membrane|||Nucleus membrane|||The SMP-LTD domain is a barrel-like domain that can bind various types of glycerophospholipids in its interior and mediate their transfer between two adjacent bilayers. http://togogenome.org/gene/10090:Gzmk ^@ http://purl.uniprot.org/uniprot/O35205 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytoplasmic granule http://togogenome.org/gene/10090:Or4f14 ^@ http://purl.uniprot.org/uniprot/A2BFL7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r115 ^@ http://purl.uniprot.org/uniprot/E9Q0E7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5bw2 ^@ http://purl.uniprot.org/uniprot/Q8VF34 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rragb ^@ http://purl.uniprot.org/uniprot/Q6NTA4 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTR/RAG GTP-binding protein family.|||Cytoplasm|||Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RagC/RRAGC or RagD/RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form: RagB/RRAGB is in its active form when GTP-bound RagB/RRAGB forms a complex with GDP-bound RagC/RRAGC (or RagD/RRAGD) and in an inactive form when GDP-bound RagB/RRAGB heterodimerizes with GTP-bound RagC/RRAGC (or RagD/RRAGD). In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway.|||Interacts with RRAGC and RRAGD; heterodimerization stabilizes RRAG proteins (By similarity). The GTP-bound form of RRAGB (in complex with the GDP-bound form of RRAGC or RRAGD) interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (By similarity). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGB, is negatively regulated by amino acids and prevents interaction with RPTOR (By similarity). Interacts with the GATOR1 complex; inactivates RRAGB (By similarity). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor. Interacts with SESN1, SESN2 and SESN3 (PubMed:25259925).|||Lysosome membrane|||The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). The Ragulator complex functions as a GEF and promotes the active GTP-bound form. The GATOR1 complex functions as a GAP and stimulates RRAGB GTPase activity to turn it into its inactive GDP-bound form, preventing mTORC1 recruitment and activation. http://togogenome.org/gene/10090:Rangap1 ^@ http://purl.uniprot.org/uniprot/P46061 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RNA1 family.|||Cytoplasm|||Detected in adult brain, liver, kidney, intestine, uterus and ovary.|||Detected in embryos at 7.5 dpc, but not at 6 dpc.|||Embryonic development is arrested around 6 dpc.|||GTPase activator for RAN. Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:18305100). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (By similarity). Required for postimplantation embryonic development (PubMed:8314081).|||Homodimer (PubMed:7891706). Interacts with RAN (PubMed:7891706). Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (By similarity). Forms a tight complex in association with RANBP2 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2 (PubMed:11853669). Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2 (PubMed:9456312, PubMed:18305100, PubMed:11853669). The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (By similarity). Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (By similarity). Interacts with TRAF6 (By similarity). Interacts with SUMO1 and SENP1 (By similarity). Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119).|||Nucleus envelope|||Phosphorylation occurs before nuclear envelope breakdown and continues throughout mitosis. Phosphorylated by the M-phase kinase cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation occurs during phases of mitosis. The phosphorylated form remains associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme, UBE2I, on nuclear pore complex (NPC) diassembly and during mitosis.|||Sumoylated (PubMed:26506250, PubMed:11853669). Sumoylation is necessary for targeting to the nuclear envelope (NE) (PubMed:16469311). Sumoylation is necessary for association with mitotic spindles and kinetochores during mitosis (By similarity). Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:9456312, PubMed:11853669). Desumoylated by HINT1 (PubMed:31088288).|||kinetochore|||nucleoplasm|||spindle http://togogenome.org/gene/10090:Jam3 ^@ http://purl.uniprot.org/uniprot/Q9D8B7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily.|||Cell junction|||Cell membrane|||Colocalizes with Jam2 near the lumen of seminiferous tubulues. Detected at junctional plaques that correspond to cell-cell contacts between spermatids and Sertoli cells (PubMed:15372036, PubMed:28617811). Detected on endothelial cells, in brain vessels and kidney glomeruli (at protein level) (PubMed:11053409, PubMed:11739175). Detected in heart, lung, liver, kidney, testis, thymus, lymph node and Peyer patch (PubMed:11053409, PubMed:11739175). Endothelial cells (PubMed:11739175).|||Detected in diploid pre-meiotic spermatocytes, haploid spermatids and elongated spermatids (PubMed:28617811, PubMed:15372036). Restricted to junctional plaques in the heads of elongated spermatids (at protein level) (PubMed:15372036).|||Important mortality during the postnatal period; about 40% of the mutant mice survive. Mutant males are infertile; they have strongly reduced testis size and fail to produce mature sperm cells. Developing spermatids fail to become polarized, and do not form acrosomes.|||Interacts with ITGAM (By similarity). Interacts with GORASP2 (PubMed:28617811).|||Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM2 to regulate different cellular processes (PubMed:15372036, PubMed:16093349). Plays a role in homing and mobilization of hematopoietic stem and progenitor cells within the bone marrow. At the surface of bone marrow stromal cells, it contributes to the retention of the hematopoietic stem and progenitor cells expressing JAM3 (PubMed:24357068). Plays a central role in leukocytes extravasation by facilitating transmigration through the endothelium (PubMed:16297198). Plays a role in spermatogenesis where JAM2 and JAM3, which are respectively expressed by Sertoli and germ cells, mediate an interaction between both cell types and play an essential role in the anchorage of germ cells onto Sertoli cells and the assembly of cell polarity complexes during spermatid differentiation (PubMed:15372036, PubMed:15994945). Also functions as a counter-receptor for ITGAM, mediating leukocyte-platelet interactions and is involved in the regulation of transepithelial migration of polymorphonuclear neutrophils (PMN) (PubMed:16093349). Plays a role in angiogenesis (PubMed:15994945). Plays a role in the regulation of cell migration (By similarity). During myogenesis, it is involved in myocyte fusion (By similarity).|||N-glycosylated.|||Promotes chemotaxis of vascular endothelial cells and stimulates angiogenesis.|||Proteolytically cleaved from endothelial cells surface into a soluble form by ADAM10 and ADAM17; the release of soluble JAM3 is increased by pro-inflammatory factors.|||S-palmitoylated by ZDHHC7. S-palmitoylation promotes expression at tight junctions.|||Secreted|||The Ig-like V-type domain mediates interaction with JAM2.|||desmosome|||tight junction http://togogenome.org/gene/10090:Zfp287 ^@ http://purl.uniprot.org/uniprot/Q9EQB9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in brain and at low levels in kidney and spleen and few hematopoietic cell lines.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Zfy1 ^@ http://purl.uniprot.org/uniprot/P10925 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family. ZFX/ZFY subfamily.|||Nucleus|||Probable transcriptional activator. Binds to the consensus sequence 5'-AGGCCY-3' (By similarity).|||The binding of ZFY to DNA is mediated by the interaction of the GGCC core base pairs with zinc fingers 12 and 13. http://togogenome.org/gene/10090:Lrrc15 ^@ http://purl.uniprot.org/uniprot/Q80X72 ^@ Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in chodrocytes (at protein level).|||In chodrocytes, expression is induced by IL1B. http://togogenome.org/gene/10090:Ppp1r17 ^@ http://purl.uniprot.org/uniprot/Q9Z2E4 ^@ Function|||PTM|||Tissue Specificity ^@ Expressed in Purkinje cells of the cerebellum, hippocampus, pons, medulla and eye.|||Inhibits phosphatase activities of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) complexes.|||Substrate for cGMP-dependent protein kinase (By similarity). Phosphorylation of Thr-72 and Thr-123 is required for its phosphatase activity. Phosphorylated by PRKG1 isoform alpha. http://togogenome.org/gene/10090:Enc1 ^@ http://purl.uniprot.org/uniprot/O35709 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein involved in the regulation of neuronal process formation and in differentiation of neural crest cells. Down-regulates transcription factor NF2L2/NRF2 by decreasing the rate of protein synthesis and not via a ubiquitin-mediated proteasomal degradation mechanism (By similarity).|||Binds to RB1. Hypophosphorylated RB1 associates with ENC1 during neuronal differentiation, while hyperphosphorylated RB1 associates with ENC1 in undifferentiating cells. Part of a complex that contains CUL3, RBX1 and ENC1 (By similarity). Interacts indirectly with KEAP1 (By similarity).|||Cytoplasm|||Expression is highly dynamic but mostly restricted to the nervous system. Outside the nervous system, expression is detected in the rostral-most somitomere of the presomitic mesoderm, at the times corresponding to the epithelialization that precedes somite formation. First detected in the brain and spinal cord of 12 PC embryos.|||Nucleus matrix|||Primarily expressed in the nervous system.|||Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and RBX1 and probably targeted for proteasome-independent degradation. Quinone-induced oxidative stress increases its ubiquitination (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Ube2r2 ^@ http://purl.uniprot.org/uniprot/Q6ZWZ2 ^@ Function|||Similarity|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes monoubiquitination and 'Lys-48'-linked polyubiquitination. May be involved in degradation of katenin.|||Belongs to the ubiquitin-conjugating enzyme family.|||When phosphorylated, interacts with beta-TrCP (BTRC). http://togogenome.org/gene/10090:Gm13040 ^@ http://purl.uniprot.org/uniprot/Q4FZF9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Klhl17 ^@ http://purl.uniprot.org/uniprot/Q6TDP3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with F-actin; the interaction disrupts the F-actin structures and leads to marked changes of neuronal morphology. Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts directly with PDZK1 (via PDZ1 domain); the interaction is important for integrity of actin cytoskeleton structures in neurons. Interacts with DLG4 and SYNGAP1. Interacts (via kelch repeats) with GRIK2 (via C-terminus); the interaction targets GRIK2 for degradation via ubiquitin-proteasome pathway. Interacts with GRIK1. Interacts with (via BTB domain) CUL3; the interaction regulates surface GRIK2 expression (By similarity).|||Postsynaptic density|||Substrate-recognition component of some cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes. The BCR(KLHL17) complex mediates the ubiquitination and subsequent degradation of GLUR6. May play a role in the actin-based neuronal function (By similarity).|||Synapse http://togogenome.org/gene/10090:Sdk1 ^@ http://purl.uniprot.org/uniprot/Q3UH53 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adhesion molecule that promotes lamina-specific synaptic connections in the retina. Expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions.|||Belongs to the sidekick family.|||Cell membrane|||Does not mediate homophilic interactions (PubMed:15703275).|||Expressed by non-overlapping subsets of retinal neurons. Sdk1 and Sdk2 are expressed in non-overlapping subsets of interneurons and retinal ganglion cells (RGCs) that form synapses in distinct inner plexiform layer (IPL) sublaminae (at protein level).|||Highly expressed in many fetal tissues, inlcuding kidney but shows markedly lower expression in adult organs. Expression in kidney is high throughout development with maximal expression occurring near birth.|||Homodimer; mediates homophilic interactions to promote cell adhesion (PubMed:15703275). Interacts (via PDZ-binding motif) with MAGI1, MAGI2, DLG2, DLG3 and DLG4 (PubMed:20219992).|||Ig-like C2-type domains 1 and 2 mediate homophilic interactions.|||Synapse|||the PDZ-binding motif mediates interaction with PDZ domain-containing proteins MAGI1, MAGI2, DLG2, DLG3 and DLG4 and is required for is required for synaptic localization in photoreceptors. http://togogenome.org/gene/10090:Psme1 ^@ http://purl.uniprot.org/uniprot/P97371|||http://purl.uniprot.org/uniprot/Q5HZK3 ^@ Function|||Induction|||Similarity|||Subunit ^@ Belongs to the PA28 family.|||By interferon gamma.|||Heterodimer of PSME1 and PSME2, which forms a hexameric ring. PSME1 can form homoheptamers (By similarity).|||Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. http://togogenome.org/gene/10090:Hpdl ^@ http://purl.uniprot.org/uniprot/Q8K248 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the 4HPPD family.|||Binds 1 Fe cation per subunit.|||May have dioxygenase activity.|||Mitochondrion http://togogenome.org/gene/10090:Med4 ^@ http://purl.uniprot.org/uniprot/Q9CQA5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 4 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Zfp184 ^@ http://purl.uniprot.org/uniprot/Q7TSH9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Mul1 ^@ http://purl.uniprot.org/uniprot/Q8VCM5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Exhibits weak E3 ubiquitin-protein ligase activity (By similarity). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (By similarity). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteasomal degradation (By similarity). Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-27' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion (By similarity). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (By similarity). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (By similarity). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (By similarity). Inhibits cell growth (By similarity). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (By similarity). Involved in the modulation of innate immune defense against viruses by inhibiting RIGI-dependent antiviral response (By similarity). Can mediate RIGI sumoylation and disrupt its polyubiquitination (By similarity).|||Expressed in cortical neurons (at protein level).|||Homooligomer. Interacts with MAP3K7/TAK1. Interacts with UBC9. Interacts with and sumoylates DNM1L. Interacts with MAVS. Interacts with TP53 (via N-terminus); the interaction leads to ubiquitination and proteasomal degradation of TP53.|||Mitochondrion outer membrane|||Peroxisome|||The zinc finger domain is required for E3 ligase activity.|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Mad2l1bp ^@ http://purl.uniprot.org/uniprot/Q9DCX1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAD2L1BP family.|||Interacts with MAD2L1.|||May function to silence the spindle checkpoint and allow mitosis to proceed through anaphase by binding MAD2L1 after it has become dissociated from the MAD2L1-CDC20 complex.|||nucleoplasm|||spindle http://togogenome.org/gene/10090:Mief2 ^@ http://purl.uniprot.org/uniprot/Q5NCS9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MID49/MID51 family.|||Does not bind ADP or other nucleotides, in contrast to MIEF1.|||Interacts with DNM1L.|||Mitochondrial outer membrane protein which regulates mitochondrial organization. It is required for mitochondrial fission and promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. Regulates DNM1L GTPase activity.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Theg ^@ http://purl.uniprot.org/uniprot/Q9JMB1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Kisimo' is a Japanese word for goddess of easy delivery.|||According to PubMed:10747865, mice lacking Theg (mutant kisimo) have virtually no spermatozoa in the lumina of seminiferous and epididymal tubules. Spermatids in the vicinity of the lumina of seminiferous tubules showed vacuolation and were occasionally phagocytosed by Sertoli cells. Elongated spermatids have abnormal or completely nonexistent flagella. No difference is seen between wild type and null mutants in the number of spermatogonia or spermatocytes. According to PubMed:12748127 null mutants appear phenotypically normal and were fertile. However, a minor but significant reduction in testes weight was observed. Morphological appearance of sperm was normal.|||Expression in testis detected after stage P20, when haploid germ cells appeared in testis.|||Interacts with CCT5.|||May be involved (but not essential) in spermatogenesis.|||Nucleus|||Testis specific (at protein level). Specifically expressed in spermatids; Sertoli cells maintain the level of expression in spermatids. If isolated spermatids are cultivated for 16 hours alone, the expression of THEG is down-regulated. May require signals from Sertoli cells to initiate changes in its gene expression through spermatogenesis. http://togogenome.org/gene/10090:Mlkl ^@ http://purl.uniprot.org/uniprot/Q9D2Y4 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated via binding to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which mediates the release of an N-terminal auto-inhibitory region (By similarity). Activation requires not only RIPK3-dependent phosphorylation but also binding to highly phosphorylated inositol phosphates (By similarity).|||Belongs to the protein kinase superfamily.|||Cell membrane|||Cytoplasm|||Highly expressed in thymus, colon, intestine, liver, spleen and lung. Expressed at much lower level in skeletal muscle, heart and kidney. Not detected in brain.|||Homooligomer (By similarity). Homotrimer; forms homotrimers on necroptosis induction (By similarity). Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK1 and RIPK3 (By similarity). Within this complex, may play a role in the proper targeting of RIPK1-RIPK3 to its downstream effector PGAM5 (By similarity). Interacts with RIPK3; the interaction is direct and promotes its phosphorylation and subsequent activation (PubMed:22265413, PubMed:23612963, PubMed:27321907, PubMed:24012422, PubMed:24095729).|||In contrast to human protein, not inhibited by necrosulfonamide, because a Trp residue is present instead of a Cys in position 85.|||Interaction with RIPK3 is species specific: mouse MLKL only interacts with mouse RIPK3 and not human RIPK3.|||No visible phenotype: mice are viable, fertile and do not developmental or homeostatic phenotype in the absence of overt stress (PubMed:23835476, PubMed:24012422). However, these mice are resistant to TNF-induced necroptosis (PubMed:23835476, PubMed:24012422). At a modestly lethal dose of influenza A virus (IAV), mice do not display increased rates of mortality (PubMed:27321907, PubMed:32200799). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Mlkl (PubMed:27819681).|||Nucleus|||Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis (PubMed:24012422, PubMed:24095729, PubMed:32200799). It also induces homotrimerization and localization to the plasma membrane (By similarity).|||Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:23835476, PubMed:27321907, PubMed:24012422, PubMed:24019532, PubMed:32200799, PubMed:32296175). Does not have protein kinase activity (PubMed:24012422). Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:23835476, PubMed:27321907, PubMed:24012422, PubMed:24019532). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (PubMed:32200799, PubMed:32296175). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (By similarity).|||The coiled coil region 2 is responsible for homotrimerization.|||The protein kinase domain is catalytically inactive but contains an unusual pseudoactive site with an interaction between Lys-219 and Gln-343 residues (PubMed:24012422, PubMed:24095729). Upon phosphorylation by RIPK3, undergoes an active conformation (PubMed:24012422, PubMed:24095729). http://togogenome.org/gene/10090:Eef1a2 ^@ http://purl.uniprot.org/uniprot/P62631 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.|||Found in a wide range of tissues.|||Monomer.|||Nucleus|||The statin expression is specific for nonproliferating cells. Its message is most abundant in G0 phase of 3T3 mouse fibroblasts, but becomes significantly reduced in G1 and S1 phases cells.|||This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.|||Trimethylated at Lys-165 by EEF1AKMT3. Mono-, di-, and trimethylated at Lys-36 by EEF1AKMT4; trimethylated form is predominant. Methylation by EEF1AKMT4 contributes to the fine-tuning of translation rates for a subset of tRNAs. Trimethylated at the N-terminus and dimethylated at Lys-55 by METTL13. http://togogenome.org/gene/10090:Prlhr ^@ http://purl.uniprot.org/uniprot/Q6VMN6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Increased nociceptive thresholds, increased stress-induced analgesia and reduced morphine tolerance.|||Interacts through its C-terminal region with the PDZ domain-containing proteins GRIP1, GRIP2 and PICK1. Interacts with PDZ domains 4 and 5 of GRIP1 and with the PDZ domain of PICK1 (By similarity).|||Receptor for prolactin-releasing peptide (PrRP). Implicated in lactation, regulation of food intake and pain-signal processing. http://togogenome.org/gene/10090:Mkx ^@ http://purl.uniprot.org/uniprot/B2RQ30|||http://purl.uniprot.org/uniprot/Q8BIA3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TALE/IRO homeobox family.|||May act as a morphogenetic regulator of cell adhesion. Participates in the early events that lead to differentiation.|||Nucleus|||Transcribed in developmentally important regions that give rise to skeletal muscle, tendons, cartilage, male gonads, and the ureteric buds of the kidney. Expressed in discrete premyogenic cell populations of the somite, in the condensing prechondrogenic mesenchymal cells of the axial skeleton, in the pretendenous cells of the tail and limbs, the testis cords of the developing male gonad, and in the metanephric kidney. http://togogenome.org/gene/10090:Tfap2e ^@ http://purl.uniprot.org/uniprot/Q6VUP9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AP-2 family.|||Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members (By similarity).|||Expressed most prominently in the mitral cell layer of the developing olfactory bulb and to a lesser extent in the granule cell layer. Also expressed in skin, articular cartilage, primary chondrocytes, and chondrosarcoma cell line SW1353.|||Nucleus|||Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-epsilon may play a role in the development of the CNS and in cartilage differentiation. http://togogenome.org/gene/10090:Or1o1 ^@ http://purl.uniprot.org/uniprot/Q7TRK4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Xiap ^@ http://purl.uniprot.org/uniprot/Q60989 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Belongs to the IAP family.|||Cytoplasm|||Expressed in small intestine crypts (at protein level) (PubMed:30389919). Expressed in bulge hair follicle stem cells, sebaceous glands and dermal papillae (at protein level) (PubMed:23788729).|||In knockout mice decreased number of Paneth cells in intestinal crypts, decreased proliferation and increased goblet cells in the intestinal villi (PubMed:30389919). Increased weight loss following intestinal wounding, increased inflammation, distorted tissue architecture, muscle thickening and greater crypt loss (PubMed:30389919). Delayed dermal wound repair (PubMed:23788729). SEPTIN4 and XIAP double knockout mice show delayed dermal wound repair and hair follicle regeneration, via increased apoptosis of hair follicle stem cells (PubMed:23788729).|||Monomer, and homodimer. Interacts (via BIR3 domain) with DIABLO/SMAC; the interaction inhibits apoptotic suppressor activity (By similarity). Interacts with HTRA2/PRSS25; the interaction inhibits apoptotic suppressor activity. Interacts with TAB1/MAP3K7IP1 and AIFM1. Interaction with DIABLO/SMAC hinders binding of TAB1/MAP3K7IP1 and AIFM1. Interacts with TCF25 and COMMD1. Interacts (via BIR3 domain) with SEPTIN4 (PubMed:30389919). Interacts with RIP1, RIP2, RIP3, RIP4, CCS and USP19. Interacts (via BIR 2 domain and BIR 3 domain) with HAX1 (via C-terminus) and this interaction blocks ubiquitination of XIAP/BIRC4. Interacts with the monomeric form of BIRC5/survivin (By similarity). Interacts with TLE3 and TCF7L2/TCF4 (By similarity). Interacts (via BIR 3 and RING domains) with PDCL3 (By similarity).|||Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis (By similarity). Acts as a direct caspase inhibitor (By similarity). Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry (By similarity). Inhibits apoptosis in intestinal crypt cells, its activity is mitigated via its interaction with SEPTIN4 isoform ARTS (PubMed:30389919). Inactivates CASP9 by keeping it in a monomeric, inactive state (By similarity). Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS, PTEN and BIRC5/survivin (PubMed:18761086, PubMed:19473982). Acts as an important regulator of innate immunity by mediating 'Lys-63'-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby transforming RIPK2 into a scaffolding protein for downstream effectors, ultimately leading to activation of the NF-kappa-B and MAP kinases signaling (PubMed:29452636). 'Lys-63'-linked polyubiquitination of RIPK2 also promotes recruitment of the LUBAC complex to RIPK2 (By similarity). Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation (By similarity). Ubiquitination of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation (By similarity). Ubiquitination of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation (By similarity). Plays a role in copper homeostasis by ubiquitinating COMMD1 and promoting its proteasomal degradation (By similarity). Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation (By similarity). Ubiquitinates and therefore mediates the proteasomal degradation of BCL2 in response to apoptosis (By similarity). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner (By similarity). Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8 (By similarity). Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES (By similarity). Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program (By similarity). Positive regulator of dermal wound repair, potentially via its interaction with SEPTIN4 (PubMed:23788729).|||Nucleus|||S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity.|||The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit caspase-3 and caspase-7, while the third BIR is involved in caspase-9 inhibition. The interactions with DIABLO/SMAC and HTRA2/PRSS25 are mediated by the second and third BIR domains (By similarity). http://togogenome.org/gene/10090:Cyp3a41b ^@ http://purl.uniprot.org/uniprot/Q9JMA7 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Detected immediately after birth in the livers of animals of both sexes, but increases with age in females, whereas it is gradually reduced in males, resulting in predominantly female-specific expression in livers.|||Endoplasmic reticulum membrane|||Expressed in liver. Also expressed in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice.|||Microsome membrane http://togogenome.org/gene/10090:Zdhhc25 ^@ http://purl.uniprot.org/uniprot/Q810M4 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DHHC palmitoyltransferase family.|||Membrane|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Plin2 ^@ http://purl.uniprot.org/uniprot/P43883|||http://purl.uniprot.org/uniprot/Q3U711 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acylated; primarily with C14, C16 and C18 fatty acids.|||Adipose tissue specific. Expressed abundantly and preferentially in fat pads.|||Belongs to the perilipin family.|||By dexamethasone.|||Lipid droplet|||Membrane|||Phosphorylation at Tyr-230 by isoform 1 of CHKA (CHKalpha2) promotes dissociation from lipid droplets: dissociation is followed by recruitment of autophagosome machinery to lipid droplets and subsequent lipid droplet lipolysis.|||Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets. http://togogenome.org/gene/10090:Apaf1 ^@ http://purl.uniprot.org/uniprot/G3XA09|||http://purl.uniprot.org/uniprot/O88879|||http://purl.uniprot.org/uniprot/Q5DU30 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||High levels in embryonic brain and liver from 11.5 dpc to 17.5 dpc.|||Highly expressed in lung and spleen, weakly in brain and kidney and not detectable in liver.|||Major isoform.|||Monomer. Oligomerizes to a heptameric ring, known as the apoptosome, upon binding of cytochrome c and dATP. Oligomeric Apaf-1 and pro-caspase-9 bind to each other via their respective NH2-terminal CARD domains and consecutively mature caspase-9 is released from the complex (By similarity). Interacts with UACA. It may also interact with Bcl-XL. Interacts with APIP. Interacts (via CARD and NACHT domains) with NAIP/BIRC1 (via NACHT domain) (By similarity). Interacts with CIAO2A (By similarity).|||Monomer. Oligomerizes upon binding of cytochrome c and dATP.|||Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP (By similarity).|||Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP.|||Physiological concentrations of calcium ions negatively affect the assembly of apoptosome by inhibiting nucleotide exchange in the monomeric form.|||The CARD domain mediates interaction with APIP.|||The monomeric form is autoinhibited in a closed conformation through a bound ADP at the nucleotide binding site. Exchange of ADP for ATP and binding of cytochrome c trigger a large conformational change where the first WD repeat region swings out, allowing the NB-ARC domain to rotate and expose the contact areas for oligomerization. http://togogenome.org/gene/10090:Cdh6 ^@ http://purl.uniprot.org/uniprot/P97326 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.|||Cell membrane|||Expressed in fetal, newborn and 7-day-old testis but not in 21-day-old or adult testis.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Zc3h12a ^@ http://purl.uniprot.org/uniprot/Q5D1E7 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZC3H12 family.|||Cytoplasm|||Cytoplasmic granule|||Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay (PubMed:26000482). Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation (PubMed:19322177, PubMed:21115689, PubMed:23185455, PubMed:26000482). Prevents aberrant T-cell-mediated immune reaction by degradation of multiple mRNAs controlling T-cell activation, such as those encoding cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and transcription factor (REL) (PubMed:23706741, PubMed:26000482, PubMed:19322177, PubMed:21115689, PubMed:23185455). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (PubMed:25282160). Together with RC3H1, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (PubMed:29244194). Self regulates by destabilizing its own mRNA (PubMed:22037600). Cleaves mRNA harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-dependent manner (PubMed:19322177, PubMed:23185455, PubMed:23706741, PubMed:26000482, PubMed:26134560). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (By similarity). Cleaves the terminal loop of a set of precursor miRNAs (pre-miRNAs) important for the regulation of the inflammatory response leading to their degradation, and thus preventing the biosynthesis of mature miRNAs (By similarity). Also plays a role in promoting angiogenesis in response to inflammatory cytokines by inhibiting the production of antiangiogenic microRNAs via its anti-dicer RNase activity (By similarity). Affects the overall ubiquitination of cellular proteins (PubMed:21115689). Positively regulates deubiquitinase activity promoting the cleavage at 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-associated factors (TRAFs), preventing JNK and NF-kappa-B signaling pathway activation, and hence negatively regulating macrophage-mediated inflammatory response and immune homeostasis (PubMed:21115689). Induces also deubiquitination of the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (By similarity). Prevents stress granules (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock, and energy deprivation (PubMed:21971051). Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state (PubMed:25934862). May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (PubMed:18178554, PubMed:19666473, PubMed:22739135). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (By similarity). Attenuates septic myocardial contractile dysfunction in response to lipopolysaccharide (LPS) by reducing I-kappa-B-kinase (IKK)-mediated NF-kappa-B activation, and hence myocardial pro-inflammatory cytokine production (PubMed:21616078).|||Expressed in CD4(+) helper T-cells (at protein level) (PubMed:29244194). Highly expressed in macrophages (PubMed:18178554). Expressed in lung, lymph nodes, spleen and thymus (PubMed:22037600). Expressed weakly in heart (PubMed:21616078). Expressed weakly in cardiomyocytes (at protein level) (PubMed:16574901). Expressed in spleen, lung, intestine, brown adipose tissue and thymus (PubMed:18682727). Weakly expressed in the heart (PubMed:16574901). Weakly expressed in cardiomyocytes (PubMed:16574901).|||Increased expression of ZC3H12A is associated with ischemic heart disease (PubMed:16574901).|||Mg(2+) is required for RNase activity (PubMed:19322177).|||Most mice die within the first 12 weeks (PubMed:21115689). Show severe inflammatory syndromes, including growth retardation, splenomegaly and lymphoadenopathy (PubMed:19322177, PubMed:21115689). show systemic inflammation characterized by T-cell and B-cell activation (PubMed:23706741). Exhibit greatly increased levels of plasma cells and infiltration of plasma cells into the lungs (PubMed:19322177, PubMed:21115689). Show elevated serum immunoglobulin levels and produce anti-nuclear autoantibodies (PubMed:19322177, PubMed:23706741). Mice show increased production of pro-inflammatory cytokine mRNAs and secreted protein levels, such as IL6, TNF and PTGS2 expression upon lipopolysaccharide (LPS) stimulation in bone marrow macrophages (BBMs) or embryonic fibroblasts, particularly in the early phase of the inflammatory response (PubMed:21115689, PubMed:26000482). Show impaired degradation of IL6 mRNA (PubMed:19322177, PubMed:21115689). Show an increased in both JNK and NF-kappa-B signaling pathway activations upon LPS stimulation (PubMed:21115689). Show an increase in global ubiquitinated protein level in splenocytes (PubMed:21115689). Display a drastic increase in both basal and LPS- or TNF-induced ubiquitination of TRAF2, TRAF3 and TRAF6 in splenocytes (PubMed:21115689). Splenocytes show spontaneously formed aggregation of stress granules (SGs) and were resistant to stress-induced apoptosis (PubMed:21971051). Heterozygous knockout mice display IL-17-dependent enhanced resistance to disseminated Candida albicans infection compared to wild-type mice (PubMed:26320658). Double knockout of ZC3H12A and RC3H1 result in embryonic developmental arrest and death; embryonic fibroblasts from these mice show a higher increase in IL6, TNF and PTGS2 expression upon LPS stimulation, both in early and late phases of the responses, compared to single knockout of either ZC3H12A or RC3H1 (PubMed:26000482). T-cell specific conditional knockout mice die within the first 8 to 17 weeks after birth with the development of severe splenomegaly and the development of a severe autoimmune inflammatory disease (PubMed:23706741). Show massive increase in effector/memory T-cells with elevated production of interferon IFNG, interleukins IL17A and IL4 in response to phorbol 13-acetate 12-myristate (PMA) (PubMed:23706741). Proteolytic cleavage is inhibited in T-cells in response to antigen stimulation (PubMed:23706741). Conditional knockout in myeloid cells show impairment in IL4-induced macrophage M2 polarization (PubMed:25934862).|||Nucleus|||Oligomer (By similarity). Found in a deubiquitination complex with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta-mediated NF-kappaB activation by promoting IKBKG or TRAF6 deubiquitination. Interacts with IKBKG; this interaction increases in response to DNA damage. Interacts with TANK; this interaction increases in response to DNA damage and serves as a bridge to anchor both TANK and USP10 into a deubiquitinating complex. Interacts with TRAF6; this interaction increases in response to DNA damage and is stimulated by TANK. Interacts with USP10; this interaction increases in response to DNA damage and serves as a bridge to anchor both TANK and USP10 into a deubiquitinating complex. Interacts with ZC3H12D. Interacts with TNRC6A. Interacts with IKBKB/IKKB. Interacts with IKBKB/IKKB (By similarity). Interacts with IKBKB/IKKB (PubMed:22037600). Interacts with BTRC; the interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (PubMed:22037600). Interacts with IRAK1; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (PubMed:22037600). Interacts with UPF1; this interaction occurs in a mRNA translationally active- and termination-dependent manner and is essential for ZC3H12A-mediated degradation of target mRNAs (PubMed:26000482). Associates with ribosomes (PubMed:26000482). Interacts with ubiquitin (PubMed:21115689).|||P-body|||Phosphorylated by IRAK1; phosphorylation is necessary for subsequent phosphorylation by the I-kappa-B-kinase (IKK) complex. Phosphorylated by I-kappa-B-kinases (IKKs) at Ser-435 and Ser-439 upon lipopolysaccharide (LPS) or IL1B stimulation in macrophages through the MyD88-dependent signaling pathway; these phosphorylations promote rapid ubiquitin proteasome-mediated degradation of ZC3H12A in macrophages and hence allows its target mRNAs, such as IL6, to escape from degradation and accumulate during the inflammatory response (PubMed:22037600).|||Proteolytically cleaved between Arg-111 and Arg-214 by MALT1 in activated T-cells; cleavage at Arg-111 is critical for promoting ZC3H12A degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling T-cell activation and Th17 cell differentiation.|||Rough endoplasmic reticulum membrane|||The C3H1-type zinc finger domain and C-terminal region are necessary for pre-miRNA binding (By similarity). The C-terminal region and proline-rich domain are necessary for oligomerization (By similarity).|||Ubiquitinated; ubiquitination is induced in response to interleukin IL1 receptor stimuli in a IKBKB/IKKB and IRAK1-dependent manner, leading to proteasome-mediated degradation (PubMed:22037600).|||Up-regulated by the transcription factor KLF4 in a interleukin IL4-dependent manner in macrophage (PubMed:25934862). Up-regulated by lipopolysaccharide (LPS) (at protein level) (PubMed:21616078). Up-regulated by chemokine CCL2 during adipocytes differentiation (PubMed:19666473). Up-regulated in activated T lymphocytes (PubMed:23185455). Up-regulated in response to lipopolysaccharide (LPS) in a MyD88-dependent manner in macrophages (PubMed:18178554, PubMed:18682727, PubMed:19322177). Up-regulated by phorbol 13-acetate 12-myristate (PMA) in primary T lymphocytes (PubMed:23185455). Up-regulated by interleukin IL17 in keratinocytes (PubMed:26320658). http://togogenome.org/gene/10090:Nob1 ^@ http://purl.uniprot.org/uniprot/Q148S3|||http://purl.uniprot.org/uniprot/Q8BW10 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOB1 family.|||May interact with UPF2 (Probable). Component of the small ribosomal subunit, ribosomal RNA processing complex (SSU RRP complex) (By similarity).|||May play a role in mRNA degradation (By similarity). Endonuclease required for processing of 20S pre-rRNA precursor and biogenesis of 40S ribosomal subunits (By similarity).|||May play a role in mRNA degradation.|||Nucleus http://togogenome.org/gene/10090:Dnah7b ^@ http://purl.uniprot.org/uniprot/A0A571BD48 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Car14 ^@ http://purl.uniprot.org/uniprot/Q9WVT6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-carbonic anhydrase family.|||Inhibited by acetazolamide.|||Membrane|||Most abundant in the kidney and heart, followed by the skeletal muscle, brain, lung and liver.|||Reversible hydration of carbon dioxide. http://togogenome.org/gene/10090:Pxk ^@ http://purl.uniprot.org/uniprot/Q8BX57 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Binds to and modulates brain Na,K-ATPase subunits ATP1B1 and ATP1B3 and may thereby participate in the regulation of electrical excitability and synaptic transmission. May not display kinase activity.|||Cell membrane|||Cytoplasm|||Intron retention.|||Isoform 1 is present in all tissues examined. Isoform 2 is found in all tissues except skeletal muscle and very low levels in spleen. Both isoforms are widely expressed throughout the nervous system however levels of isoform 2 are higher in purified hippocampal and cortical neurons whereas glial cells express more isoform 1 than isoform 2.|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Dll3 ^@ http://purl.uniprot.org/uniprot/O88516|||http://purl.uniprot.org/uniprot/Q3UND5 ^@ Caution|||Disease Annotation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A truncating mutation in Dll3 is the cause of the pudgy (pu) phenotype. Pudgy mice exhibit patterning defects at the earliest stages of somitogenesis. Adult pudgy mice present severe vertebral and rib deformities.|||Can bind and activate Notch-1 or another Notch receptor.|||Inhibits primary neurogenesis. May be required to divert neurons along a specific differentiation pathway. Plays a role in the formation of somite boundaries during segmentation of the paraxial mesoderm.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Predominantly expressed in the neuroectoderm and paraxial mesoderm during embryogenesis.|||The DSL domain is required for binding to the Notch receptor.|||Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation. http://togogenome.org/gene/10090:Pramel5 ^@ http://purl.uniprot.org/uniprot/Q7TPY4 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Mrpl58 ^@ http://purl.uniprot.org/uniprot/Q8R035 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prokaryotic/mitochondrial release factor family. Mitochondrion-specific ribosomal protein mL62 subfamily.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Essential peptidyl-tRNA hydrolase component of the mitochondrial large ribosomal subunit (PubMed:20869366). Acts as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion, possibly in case of abortive elongation. May be involved in the hydrolysis of peptidyl-tRNAs that have been prematurely terminated and thus in the recycling of stalled mitochondrial ribosomes (By similarity).|||In contrast to other members of the family, lacks the regions that come into close contact with the mRNA in the ribosomal A-site and determine the STOP codon specificity, explaining the loss of codon specificity for translation release factor activity.|||Methylation of glutamine in the GGQ triplet by HEMK1.|||Mitochondrion http://togogenome.org/gene/10090:C5ar2 ^@ http://purl.uniprot.org/uniprot/E9PVQ2|||http://purl.uniprot.org/uniprot/E9QQ21|||http://purl.uniprot.org/uniprot/Q8BW93 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the chemokine-like receptor (CMKLR) family.|||Cell membrane|||Highly expressed in liver and spleen. Lower levels in intestine, brain and kidney. Also expressed in adipose tissues with highest levels in gonadal and ingual fat depots. Lower levels in brown tissue.|||Interacts with C3 (the anaphylatoxin peptide C3a and the adipogenic hormone ASP); the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of GPR77, recruitment of ARRB2 to the cell surface and endocytosis of GRP77.|||Membrane|||Receptor for the chemotactic and inflammatory C3a, C4a and C5a anaphylatoxin peptides and also for their dearginated forms ASP/C3adesArg, C4adesArg and C5adesArg respectively. Couples weakly to G(i)-mediated signaling pathways (By similarity). http://togogenome.org/gene/10090:Nt5e ^@ http://purl.uniprot.org/uniprot/Q0VEE0|||http://purl.uniprot.org/uniprot/Q61503 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 5'-nucleotidase family.|||Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside (PubMed:8224905). Hydrolyzes IMP (PubMed:8224905). Shows a preference for ribonucleotide monophosphates over their equivalent deoxyribose forms (By similarity). Although AMP is the preferred substrate can also hydrolyze UMP, GMP, CMP, dAMP, dCMP, dTMP, NAD and NMN (By similarity).|||Cell membrane|||Expressed at high levels in the placenta, kidney, lung and stomach and at lower levels in the thymus, spleen, skeletal muscle and esophagus.|||Homodimer.|||Membrane http://togogenome.org/gene/10090:Ssh3 ^@ http://purl.uniprot.org/uniprot/Q8K330 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||Does not bind to, or colocalize with, filamentous actin.|||Expressed in brain, small intestine and testis. Also expressed at lower levels in heart, kidney, liver, spleen and thymus.|||Expressed in the nervous system and epithelial tissues of the trachea at 14.5 dpc.|||Nucleus|||Protein phosphatase which may play a role in the regulation of actin filament dynamics. Can dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly.|||Tyrosine phosphatase activity has not been demonstrated for this protein to date.|||cytoskeleton http://togogenome.org/gene/10090:Mc5r ^@ http://purl.uniprot.org/uniprot/G3UWB6|||http://purl.uniprot.org/uniprot/P41149|||http://purl.uniprot.org/uniprot/Q496T0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. This receptor is a possible mediator of the immunomodulation properties of melanocortins.|||Skin, adrenal gland, skeletal muscle, bone marrow, spleen, thymus, gonads, uterus and brain. http://togogenome.org/gene/10090:Rbm42 ^@ http://purl.uniprot.org/uniprot/Q91V81 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM RBM42 family.|||Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA.|||Cytoplasm|||Expressed in cell lines (at protein level). Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Interacts with HNRNPK.|||Nucleus http://togogenome.org/gene/10090:Enpp6 ^@ http://purl.uniprot.org/uniprot/Q8BGN3 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 2 (P2) and P4, is detected in immature oligodendrocytes, where it was predominantly found both in the processes and cell bodies. In contrast, at P12 and P14, it is found mainly in myelin sheaths.|||Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells (PubMed:15788404, PubMed:26888014). Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids (PubMed:15788404). In vitro, hydrolyzes only choline-containing lysophospholipids, such as sphingosylphosphorylcholine (SPC), platelet-activating factor (PAF) and lysoPAF, but not other lysophospholipids (PubMed:15788404).|||Enpp6 knockout mice give birth according to the Mendelian rule and are apparently normal. Mice exhibit mild symptoms of fatty liver and are more susceptible to a choline-deficient diet and exhibit severe fatty liver phenotypes at the early stage.|||Homodimer; disulfide-linked (PubMed:26888014). Homotetramer (PubMed:26888014).|||Inhibited by EDTA and EGTA in vitro.|||Predominantly expressed in kidney with a lesser expression in brain and heart (PubMed:15788404, PubMed:26888014). In the brain and spinal cord, mainly expressed in the white matter. In oligodendrocytes, is predominantly detected in the myelin sheath. In the kidney, is predominantly expressed in the luminal side of the renal tubule in the cortex and in the proximal renal tubules. It is expressed in liver sinusoidal endothelial cells (PubMed:26888014). http://togogenome.org/gene/10090:Tnfsf12 ^@ http://purl.uniprot.org/uniprot/O54907|||http://purl.uniprot.org/uniprot/Q5F2A0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor family.|||Binds to FN14 and possibly also to TNRFSF12/APO3. Weak inducer of apoptosis in some cell types. Mediates NF-kappa-B activation. Promotes angiogenesis and the proliferation of endothelial cells. Also involved in induction of inflammatory cytokines. Promotes IL8 secretion (By similarity).|||Cell membrane|||Homotrimer. Interacts with the angiogenic factor AGGF1/VG5Q (By similarity).|||Secreted|||The soluble form is produced from the membrane form by proteolytic processing.|||Widely expressed. http://togogenome.org/gene/10090:Aldh1l1 ^@ http://purl.uniprot.org/uniprot/Q8R0Y6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytosolic 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide (PubMed:31624291). May also have an NADP(+)-dependent aldehyde dehydrogenase activity towards formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde (By similarity).|||Highly expressed in liver (at protein level) (PubMed:31624291). Also expressed in pancreas, brain and lung (at protein level) (PubMed:31624291).|||Homotetramer.|||Homozygous knockout mice are viable, fertile, develop normally and do not display overt phenotype (PubMed:31624291). However, they have metabolic signs of folate deficiency like the accumulation of formiminoglutamate (PubMed:31624291). Mice show reduced hepatic folate pools with a strong accumulation of (6S)-10-formyltetrahydrofolate and a significant drop in tetrahydrofolate levels (PubMed:31624291). This is associated with a strong decrease of glycine levels as well as levels of several glycine conjugates (PubMed:31624291).|||In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.|||In the N-terminal section; belongs to the GART family.|||Phosphopantetheinylation at Ser-354 by AASDHPPT is required for the formyltetrahydrofolate dehydrogenase activity.|||The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity. It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2.|||The N-terminal hydrolase domain has an NADP-independent formyltetrahydrofolate hydrolase activity, releasing formate and tetrahydrofolate.|||The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2. The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2.|||cytosol http://togogenome.org/gene/10090:Myh8 ^@ http://purl.uniprot.org/uniprot/P13542 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).|||Muscle contraction.|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||myofibril http://togogenome.org/gene/10090:Rbbp4 ^@ http://purl.uniprot.org/uniprot/Q60972 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.|||Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin (By similarity). Subunit of the chromatin assembly factor 1 (CAF-1) complex, which is composed of RBBP4, CHAF1B and CHAF1A (By similarity). Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7 (By similarity). The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SUDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex (By similarity). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (By similarity) The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (By similarity). The NuRD complex may also interact with MBD3L1 and MBD3L2 (By similarity). Component of the PRC2 complex, which consists of the core subunits EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:19026780). Forms a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (By similarity). Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19; PHF19 stabilizes the dimeric structure which enhances PRC2 interaction with chromatin (By similarity). Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1 (isoform 2), BPTF, RBBP4 and RBBP7 (PubMed:10866654). Within the complex interacts with isoform 2 of SMARCA1 (By similarity). Component of the BPFT-SMARCA1 complex at least composed of SMARCA1 (isoform 1), BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin (By similarity). Within the complex interacts with isoform 1 of SMARCA1 (By similarity). Interacts with the ISWI chromatin remodeling complex component SMARCA5; the interaction is direct (By similarity). Interacts with the viral protein-binding domain of the retinoblastoma protein (RB1) (By similarity). Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2 (By similarity). The complex exists in quiescent cells where it represses cell cycle-dependent genes (By similarity). It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (PubMed:28554894). Interacts with ZNF827; the interaction is direct and recruits RBBP4 to telomeres (By similarity). Interacts with MTA1; the interaction is direct and mutually exclusive with binding histone H4 (By similarity). Interacts with ARMC12 (via ARM domains) (By similarity). Interacts with BRCA1 (By similarity). Interacts with CDK2AP1 (By similarity). Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP (PubMed:10866654). Interacts with ERCC6 (By similarity). Interacts with HDAC7 (PubMed:10984530). Interacts with PHF6 (By similarity). Interacts with PWWP2B (PubMed:34180153). Interacts with SPEN/MINT (By similarity). Interacts with SUV39H1 (PubMed:11788710).|||Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; the PRC2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.|||Higher levels in brain, thymus, lung, spleen, kidney, testis, and ovary/uterus; lower levels in heart, liver, and muscle.|||Nucleus|||telomere http://togogenome.org/gene/10090:Pfn1 ^@ http://purl.uniprot.org/uniprot/P62962|||http://purl.uniprot.org/uniprot/Q3U7V7|||http://purl.uniprot.org/uniprot/Q5SX50 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the profilin family.|||Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR (By similarity).|||Found in a complex with XPO6, Ran, ACTB and PFN1 (By similarity). Interacts with HTT (By similarity). Interacts with VASP (By similarity). Interacts with SH3BGRL (By similarity). Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio (By similarity). Interacts with ACTMAP (By similarity).|||Phosphorylation at Ser-138 reduces its affinity for G-actin and blocks its interaction with HTT, reducing its ability to inhibit androgen receptor (AR) and HTT aggregation.|||cytoskeleton http://togogenome.org/gene/10090:Kcnc2 ^@ http://purl.uniprot.org/uniprot/A0A1W2P796|||http://purl.uniprot.org/uniprot/Q14B80 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.2/KCNC2 sub-subfamily.|||Cell membrane|||Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1 (PubMed:10531438). Interacts with KCNC1 (PubMed:10531438, PubMed:12000114). Homotetramer or heterotetramer channel activity is regulated by association with modulating ancillary subunits such as KCNE1, KCNE2 and KCNE3, creating a functionally diverse range of channel complexes. Interacts with KCNE1, KCNE2 and KCNE3 (By similarity).|||Inhibited by millimolar levels of tetraethylammonium (TEA). Contrary to other channels, inhibited only by millimolar levels of 4-aminopyridine (4-AP). Inhibited by Stichodactyla helianthus peptide ShK.|||Membrane|||Mice are healthy, grow normally, are fertile and show no evidence of severe sensory or motor abnormalities (PubMed:11124984). Show increased seizure susceptibility and reduced long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Thalamocortical neurons show a strong attenuation in maximal peak firing rates, with larger spikes and slower action potential repolarization (PubMed:17761775). Neocortical GABAergic interneurons display broader spikes and sustain lower trains of high-frequency spikes without accommodation or spike doublets in rapid succession (PubMed:11124984, PubMed:22539821). Histamine H2 receptor- and PKA-induced hippocampal inhibitory interneurons display no maximal sustainable firing frequency modulation (PubMed:10903572). Double knockout of KCNC2 and KCNC1 exhibited disrupted daily rhythms in wheel-running behavior (PubMed:21414897). Display smaller outward currents and slower deactivation in starburst amacrine cells compared with KCNC2 knockout mice (PubMed:15317859). Neocortical GABAergic interneuron terminals display also a reduced rate of spike repolarization, broader spike, increased calcium influx and release of GABA neurotransmitter (PubMed:15917463). Suprachiasmatic nucleus (SCN) neurons display a reduction in the magnitude of fast delayed rectifier potassium currents, wider action potentials, reduced spontaneous firing activity during the day and reduced NMDA-evoked increase firing responses during the night (PubMed:21414897).|||Perikaryon|||Phosphorylated by PKA in cortical synaptosomes. cAMP-dependent phosphorylation inhibits channel activity (By similarity). Histamine H2 receptor- and PKA-induced phosphorylation extends action potential spike duration, reduces action potential spike amplitude, sustains maximum firing frequency in hippocampal interneurons; also reduces the incidence of high-frequency oscillations in hippocampal CA3 pyramidal cell layers (PubMed:10903572).|||Postsynaptic cell membrane|||Presynaptic cell membrane|||Synapse|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system (PubMed:10561420, PubMed:10414303, PubMed:11124984, PubMed:10903572, PubMed:11506885, PubMed:15317859, PubMed:15917463, PubMed:17761775, PubMed:21414897). Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly (PubMed:10414303). Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (By similarity). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:10531438, PubMed:12000114). Channel properties may be modulated by either the association with ancillary subunits, such as KCNE1, KCNE2 and KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in thalamocortical and suprachiasmatic nucleus (SCN) neurons, in hippocampal and neocortical interneurons and in retinal ganglion cells (PubMed:10561420, PubMed:10903572, PubMed:11506885, PubMed:17761775). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner (PubMed:10903572). Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release (PubMed:15917463). Required for long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (PubMed:21414897).|||Weakly expressed in the brain at 14 dpc (at protein level) (PubMed:21912965). Expressed in the brain at 14 dpc (PubMed:21912965).|||Weakly expressed in the brain at postnatal age day 7 (P7) and increased at P60 (PubMed:21912965). Not detectable in newborn hippocampus. Expressed weakly at P7 in the early developing hippocampus, increasing progressively and reaching a plateau of expression at P14 that is maintained throughout P51. Expressed in paravalbumin- and somatostain-containing inhibitory interneurons of the hippocampus; in the CA1/CA3 stratum oriens-alveus and stratum pyramidale and in cells within the hilus and subgranular layer of the dentate gyrus (DG) (PubMed:12000114, PubMed:10903572). Strongly expressed in parvalbumin (PV)-containing fast-spiking GABAergic inhibitor interneurons in deep cortical layers V and VI (PubMed:10531438). Also expressed in non-fast-spiking calbindin (CB)- and/or somatostatin (SOM)-containing interneurons in deep cortical layers V and VI (PubMed:10531438). Expressed in starburst amacrine cells of the retina in the inner nuclear layer (INL) and ganglion cell layer (GCL) (PubMed:15317859). Expressed in the suprachiasmatic nucleus (SCN) (at protein level) (PubMed:15852012, PubMed:21414897). Expressed in the early developing brain, increasing progressively until P14 (PubMed:21912965).|||axon|||dendrite|||synaptosome http://togogenome.org/gene/10090:Lratd1 ^@ http://purl.uniprot.org/uniprot/Q9D650 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LRATD family.|||Cytoplasm|||May play a role in cell morphology and motility. http://togogenome.org/gene/10090:Prima1 ^@ http://purl.uniprot.org/uniprot/Q810F0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Cell membrane|||Interacts with ACHE, probably through disulfide bonds.|||Predominantly expressed in the central nervous system, including in the brain. Also expressed in muscle, heart and kidney. Isoform 1 may be predominant in the cortex and striatum, while isoform 2 is more abundant in the cerebellum.|||Required to anchor acetylcholinesterase (ACHE) to the basal lamina of the neuromuscular junction and to the membrane of neuronal synapses in brain. Also able to organize ACHE into tetramers.|||Synapse|||The proline-rich attachment domain (PRAD) binds the AChE catalytic subunits. http://togogenome.org/gene/10090:Or5t7 ^@ http://purl.uniprot.org/uniprot/Q8VFL9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Rpa2 ^@ http://purl.uniprot.org/uniprot/Q62193 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Also plays a role in base excision repair (BER) probably through interaction with UNG. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance.|||Belongs to the replication factor A protein 2 family.|||Component of the replication protein A complex (RPA/RP-A), a heterotrimeric complex composed of RPA1, RPA2 and RPA3. Interacts with PRPF19; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it ubiquitinates the replication protein A complex (RPA) (By similarity). Interacts with SERTAD3. Interacts with TIPIN (PubMed:17141802). Interacts with TIMELESS (PubMed:17141802). Interacts with PPP4R2; the interaction is direct, DNA damage-dependent and mediates the recruitment of the PP4 catalytic subunit PPP4C (By similarity). Interacts (hyperphosphorylated) with RAD51 (By similarity). Interacts with SMARCAL1; the interaction is direct and mediates the recruitment to the RPA complex of SMARCAL1 (By similarity). Interacts with RAD52 and XPA; those interactions are direct and associate RAD52 and XPA to the RPA complex (By similarity). Interacts with FBH1 (By similarity). Interacts with ETAA1; the interaction is direct and promotes ETAA1 recruitment at stalled replication forks (By similarity). Interacts with DDI2 (By similarity). Interacts (in unphosphorylated form via N-terminus) with EIF4EBP3; the interaction enhances EIF4EBP3-mediated inhibition of EIF4E-mediated mRNA nuclear export (By similarity).|||DNA damage-induced 'Lys-63'-linked polyubiquitination by PRPF19 mediates ATRIP recruitment to the RPA complex at sites of DNA damage and activation of ATR. Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination.|||Differentially phosphorylated throughout the cell cycle, becoming phosphorylated at the G1-S transition and dephosphorylated in late mitosis. Mainly phosphorylated at Ser-23 and Ser-29, by cyclin A-CDK2 and cyclin B-CDK1, respectively during DNA replication and mitosis. Dephosphorylation may require the serine/threonine-protein phosphatase 4. Phosphorylation at Ser-23 and Ser-29 is a prerequisite for further phosphorylation. Becomes hyperphosphorylated on additional residues including Ser-4, Ser-8, Thr-21 and Ser-33 in response to DNA damage. Hyperphosphorylation is mediated by ATM, ATR and PRKDC. Primarily recruited to DNA repair nuclear foci as a hypophosphorylated form it undergoes subsequent hyperphosphorylation, catalyzed by ATR. Hyperphosphorylation is required for RAD51 recruitment to chromatin and efficient DNA repair. Phosphorylation at Thr-21 depends upon RFWD3 presence.|||Nucleus|||PML body http://togogenome.org/gene/10090:Txlng ^@ http://purl.uniprot.org/uniprot/Q3TS51|||http://purl.uniprot.org/uniprot/Q3TT61|||http://purl.uniprot.org/uniprot/Q8BHN1 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 16.5 dpc, expressed in osteoblasts surrounding newly formed trabecular bone. At postnatal day 2, detected in most osteoblasts and lining cells, and also strongly expressed in osteocytes. By postnatal week 4, strongly expressed in osteocytes (at protein level).|||Belongs to the taxilin family.|||Binds to the C-terminal coiled coil region of syntaxin family members STX1A, STX3A and STX4A (By similarity). Forms a heterodimer with ATF4 in osteoblasts.|||By LPS.|||May be involved in intracellular vesicle traffic (By similarity). Inhibits ATF4-mediated transcription, possibly by dimerizing with ATF4 to form inactive dimers that cannot bind DNA. May be involved in regulating bone mass density through an ATF4-dependent pathway. May be involved in cell cycle progression.|||Nucleus membrane|||cytosol http://togogenome.org/gene/10090:Ly6g6d ^@ http://purl.uniprot.org/uniprot/Q9Z1Q3 ^@ PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in embryonic tissue and adult lung, kidney, brain, liver and spleen.|||Homodimer.|||O-glycosylated.|||filopodium http://togogenome.org/gene/10090:Palm3 ^@ http://purl.uniprot.org/uniprot/A2TJV2 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-binding protein, which may act as a adapter in the Toll-like receptor (TLR) signaling.|||Belongs to the paralemmin family.|||Cell membrane|||Cytoplasm|||Interacts with SIGIRR.|||Intron retention.|||Palmitoylated on Cys-728 and Cys-730 and prenylated on Cys-731; which is required for membrane association. http://togogenome.org/gene/10090:Lipt1 ^@ http://purl.uniprot.org/uniprot/Q8C894|||http://purl.uniprot.org/uniprot/Q8VCM4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LplA family.|||Catalyzes the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes.|||Mitochondrion http://togogenome.org/gene/10090:Spam1 ^@ http://purl.uniprot.org/uniprot/P48794|||http://purl.uniprot.org/uniprot/Q5D1J0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 56 family.|||Cell membrane|||Involved in sperm-egg adhesion. Upon fertilization sperm must first penetrate a layer of cumulus cells that surrounds the egg before reaching the zona pellucida. The cumulus cells are embedded in a matrix containing hyaluronic acid which is formed prior to ovulation. This protein aids in penetrating the layer of cumulus cells by digesting hyaluronic acid.|||Membrane http://togogenome.org/gene/10090:Sprr2h ^@ http://purl.uniprot.org/uniprot/O70559 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane (By similarity).|||Cytoplasm|||During early pregnancy, low expression detected in uterus at 1 dpc.|||Expressed weakly in uterus. http://togogenome.org/gene/10090:Clcn4 ^@ http://purl.uniprot.org/uniprot/A0A1B0GT29|||http://purl.uniprot.org/uniprot/Q3LRV6|||http://purl.uniprot.org/uniprot/Q61418|||http://purl.uniprot.org/uniprot/Q8CBL5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family.|||Belongs to the chloride channel (TC 2.A.49) family. ClC-4/CLCN4 subfamily.|||Early endosome membrane|||Endoplasmic reticulum membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Late endosome membrane|||Lysosome membrane|||Membrane|||Predominantly present in excitable tissues such as nervous system and skeletal muscle. Not detected in heart.|||Recycling endosome membrane|||Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (By similarity). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity). http://togogenome.org/gene/10090:Cfap221 ^@ http://purl.uniprot.org/uniprot/A9Q751 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PCDP1 family.|||Cytoplasm|||Expressed in testis, specifically in developing spermatocytes and spermatids but not in immature spermatogonia. Expressed in the ciliated respiratory epithelial cells lining the sinuses, trachea and bronchi (at protein level).|||Expression in testis starts at P20.|||Interacts with calmodulin; calcium-dependent.|||May play a role in cilium morphogenesis.|||Mice lacking Pcdp1 have several phenotypes associated with primary ciliary diskinesia, including hydrocephalus, male infertility and respiratory abnormalities. Hydrocephalus is observed on the B6 background but not on the 129 background. Male infertility is observed on both backgrounds and is due to an absence of mature spermatozoa in the seminiferous tubules.|||cilium axoneme|||cytoskeleton http://togogenome.org/gene/10090:Kif12 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VK29|||http://purl.uniprot.org/uniprot/Q9D2Z8 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Expressed in the liver.|||cytoskeleton http://togogenome.org/gene/10090:Atp5c1 ^@ http://purl.uniprot.org/uniprot/Q3UD06|||http://purl.uniprot.org/uniprot/Q8C2Q8|||http://purl.uniprot.org/uniprot/Q91VR2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase gamma chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding.|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and the central stalk which is part of the complex rotary element. The gamma subunit protrudes into the catalytic domain formed of alpha(3)beta(3). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or6c5b ^@ http://purl.uniprot.org/uniprot/A0A0N4SVC3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plac9 ^@ http://purl.uniprot.org/uniprot/Q8K262 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PLAC9 family.|||Highly expressed in placenta, and weakly in ovary, testis, and lung.|||Secreted http://togogenome.org/gene/10090:Ckb ^@ http://purl.uniprot.org/uniprot/Q04447 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATP:guanido phosphotransferase family.|||Cell membrane|||Conditional deletion in adipocytes leads to defective adaptive thermogenesis: defects are caused by abolition of the futile creatine cycle, thereby reducing whole-body energy expenditure and leading to predisposition to obesity.|||Dimer of identical or non-identical chains, which can be either B (brain type) or M (muscle type). With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain. Interacts with SLC12A6 (via C-terminus); the interaction may be required for SLC12A6 potassium-chloride cotransport activity (By similarity).|||Expressed in hippocampus and corpus callosum (at protein level).|||Mitochondrion|||Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:33597756). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (PubMed:33597756). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (PubMed:33597756).|||Strongly up-regulated in response to cold in fat cells; expression is dependent on cAMP.|||The internal MTS-like signal (iMTS-L) mediates targeting to mitochondria thermogenic fat cells.|||cytosol http://togogenome.org/gene/10090:Afdn ^@ http://purl.uniprot.org/uniprot/Q9QZQ1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (By similarity). May play a key role in the organization of epithelial structures of the embryonic ectoderm (PubMed:10477764). Essential for the organization of adherens junctions (By similarity).|||Highly expressed at restricted set of epithelial structures and highly concentrated at their junctional complex regions. At 6.5 dpc, localized at the most apical regions of cell-cell adhesion sites of the entire embryonic ectoderm; not detected in the extraembryonic regions. At 7.0 dpc, expressed in the primitive streak and the migrating paraxial mesoderm. At 7.5 dpc, highly expressed at the junctional complex regions in the primitive streak region (neuroepithelium) and the neural fold/grove region, but hardly detected in other areas of the ectoderm. By 8.5 dpc, highly expressed in the tail bud, somites and the paraxial mesoderm, concentrated at the junctional complex regions in neural tube, somites and pericardioperitoneal canal.|||Homodimer. Interacts with F-actin, nectin and NECTIN3. Essential for the association of nectin and E-cadherin. Isoform 2/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1, RIT2, NRXN1 and BCR (By similarity). Interacts with ADAM10; the interaction locks ADAM10 at adherens junctions following ADAM10 recruitment to adherens junctions by TSPAN33 (PubMed:30463011).|||Isoform 1 is expressed only in a restricted set of epithelial structures during early embryogenesis.|||Mice show developmental defects at stages during and after gastrulation, including disorganization of the ectoderm, impaired migration of the mesoderm and loss of somites and other structures derived from both the ectoderm and mesoderm. Cell-cell adherens juntions and tight junctions are improperly organized in the ectoderm-derived cells. No redundancy exists in the function of afadin during gastrulation.|||adherens junction http://togogenome.org/gene/10090:Trp53rka ^@ http://purl.uniprot.org/uniprot/Q5U452 ^@ Similarity ^@ Belongs to the protein kinase superfamily. BUD32 family. http://togogenome.org/gene/10090:Alyref2 ^@ http://purl.uniprot.org/uniprot/Q9JJW6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Arginine methylation reduces RNA binding and enhances mRNA transfer to the NXF1-NXT1 heterodimer for nuclear export.|||Cytoplasm|||Export adapter involved in spliced and unspliced mRNA nuclear export. Binds mRNA which is transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway); enhances NXF1-NXT1 RNA-binding activity.|||Interacts (via N-terminus and RRM domain) with DDX39B and th NXF1-NXT1 heterodimer. Interacts with HHV-1 ICP27 and HVS ORF57 proteins.|||Nucleus|||The RRM domain and the N-terminal region (15-58) seem to be involved in RNA binding. http://togogenome.org/gene/10090:Tpr ^@ http://purl.uniprot.org/uniprot/F6ZDS4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TPR family.|||Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Plays a limited role in the regulation of nuclear protein export. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases (By similarity).|||Cytoplasm|||Expressed both maternally and zygotically. Expressed at the mid two-cell stage and in the embryo at 7, 11, 15 and 17 dpc.|||Expressed in the heart, liver, kidney, spleen, lung and skeletal muscles.|||Homodimer. Part of the nuclear pore complex (NPC). Associates with the XPO1/CRM1-mediated nuclear export complex, the Importin alpha/Importin beta receptor and the dynein 1 complex. Interacts (via C-terminal domain) with the KPNB1; the interaction occurs in a RanGTP-dependent manner. Interacts (via C-terminal region and phosphorylated form) with MAPK1/ERK2 (via phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation. Interacts with MAPK3/ERK1; the interaction increases following EGF stimulation. Interacts (via coiled coil region) with NUP153; the interaction is direct. Interacts with HSF1; the interaction increases in a stress-responsive manner and stimulates export of stress-induced HSP70 mRNA. Interacts with huntingtin/HTT; the interaction is inhibited by aggregated huntingtin/HTT forms with expanded polyglutamine stretch. Interacts with MAD1L1 (via N-terminal region), MAD2L1, and TTK; the interactions occurs in a microtubule-independent manner. Interacts (via middle region) with DYNLL1. Interacts with DCTN1, dynein, NUP153 and tubulin. Interacts with MTA1 (By similarity). Interacts with IFI204 (via C-terminal region). Interacts with IFI203.|||Nucleus|||Nucleus envelope|||Nucleus membrane|||Phosphorylated. Phosphorylation occurs on serine and threonine residues (comprised in the C-terminal region) by MAPK1/ERK2 and stabilizes the interaction between these two proteins (By similarity).|||The N-terminal domain mediates intranuclear attachment to the nuclear pore complex. The C-terminal domain mediates its nuclear import (By similarity).|||kinetochore|||nuclear pore complex|||spindle http://togogenome.org/gene/10090:Fyco1 ^@ http://purl.uniprot.org/uniprot/Q8VDC1 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can form homodimers. Interacts (via C-terminus) with MAP1LC3B. Interacts with RAB7A; the interaction with RAB7A induces FYCO1 recruitment to late endosomal/lysosomal compartments.|||Contaminating sequence. Potential poly-A sequence.|||Endosome|||Expressed in heart and testis. Expressed in the eye lens.|||Lysosome|||May mediate microtubule plus end-directed vesicle transport.|||autophagosome http://togogenome.org/gene/10090:Acvr1 ^@ http://purl.uniprot.org/uniprot/P37172 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:10479450, PubMed:15531373, PubMed:21945937). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A ors ACVR2B. Upon binding of ligands such as BMP7 or BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain. In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal. In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor. Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (PubMed:25413979, PubMed:10479450, PubMed:15531373, PubMed:21945937) (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (PubMed:31800957).|||Deletion mutants show a recessive embryonic lethality. At 7.0 dpc, mutant embryos did not show any special abnormalities except a smaller size. However, at 8.0 dpc, mesoderm formation is initiated but its development is arrested around the mid/late streak stage (PubMed:10479450). In an osteoblast-specific manner loss of BMP signaling via ACVR1 directs osteoblasts to increase endogenous bone mass (PubMed:21945937). Additionally, mice lacking ACVR1 in cartilage show reduced SMAD responses, but also decreased p38 MAPK activation (PubMed:25413979).|||Highly expressed in bone during developmental stages (PubMed:21945937). Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells.|||Highly expressed in the node and midline and weakly expressed in 8.5 dpc embryos and in the lateral plate mesoderm.|||Interacts with FKBP1A (By similarity). Interacts with FCHO1 (By similarity). Interacts with CLU. Interacts with type II receptors AMHR2 and ACVR2A (By similarity). Interacts with BMP7 (By similarity). Interacts with BMP9 (By similarity). Interacts with BMP6 (when glycosylated); the interaction may induce HAMP expression (PubMed:31800957). Interacts with TSC22D1/TSC-22 (By similarity).|||Membrane http://togogenome.org/gene/10090:Zbtb42 ^@ http://purl.uniprot.org/uniprot/Q811H0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family. ZBTB18 subfamily.|||Cytoplasm|||Highly expressed in skeletal muscle and ovary (at protein level). Low expression in brain, lung, spleen, liver and heart (at protein level). Not detected in kidney and intestines (at protein level). Also observed in testis and, at lower levels, in stomach and nervous system.|||Transcriptional repressor. Specifically binds DNA and probably acts by recruiting chromatin remodeling multiprotein complexes.|||nucleoplasm http://togogenome.org/gene/10090:Arsk ^@ http://purl.uniprot.org/uniprot/A0A0R4J1N2|||http://purl.uniprot.org/uniprot/Q9D2L1 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Catalyzes the hydrolysis of pseudosubstrates such as p-nitrocatechol sulfate and p-nitrophenyl sulfate (By similarity). Catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-glucuronate residues of chondroitin sulfate, heparin and heparitin sulfate (PubMed:32856704). Acts selectively on 2-sulfoglucuronate and lacks activity against 2-sulfoiduronate (By similarity).|||Lysosome|||Mice accumulate significant amounts of heparan sulfate, which exhibits glucuronate-2-O-sulfated non-reducing ends, particularly in brain and kidney.|||N-glycosylated with both high mannose and complex type sugars.|||Secreted|||The 75-kDa precursor undergoes proteolytic processing to yield a 23 kDa form.|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Krt4 ^@ http://purl.uniprot.org/uniprot/P07744 ^@ Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the dorsal and ventral epithelium of the tongue. Highest expression levels are detected in the suprabasal layer with low levels detected in the basal cell layer. Within the suprabasal layer expression is highest in the spinous cells, decreases in the granular cells and is not detected in the stratum corneum.|||Heterotetramer of two type I and two type II keratins. Keratin-4 is generally associated with keratin-13.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Nubpl ^@ http://purl.uniprot.org/uniprot/Q9CWD8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Mrp/NBP35 ATP-binding proteins family.|||Binds 1 [4Fe-4S] cluster.|||Mitochondrion|||Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I). May deliver of one or more Fe-S clusters to complex I subunits (By similarity). http://togogenome.org/gene/10090:Mrps25 ^@ http://purl.uniprot.org/uniprot/Q9D125 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS25 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Gimap6 ^@ http://purl.uniprot.org/uniprot/Q8K349 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.|||Expressed in thymus (in thymocytes), spleen (in splenocytes), lymph node and lung.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||cytosol http://togogenome.org/gene/10090:Zup1 ^@ http://purl.uniprot.org/uniprot/Q3T9Z9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C78 family. ZUFSP subfamily.|||C2H2-type zinc finger 4 is a ubiquitin-binding zinc finger (UBZ) and required for polyubiquitin binding, possibly binding the proximal ubiqutin, and for catalytic activity. C2H2-type zinc fingers 1-3 are required for localization to sites of DNA damage.|||Cytoplasm|||Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains. Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains. Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress.|||Interacts with RPA1 and RPA2.|||Nucleus|||The motif interacting with ubiquitin (MIU) and ZUFSP ubiquitin-binding domain (zUBD, also called ZUFSP helical arm ZHA) are responsible for binding the distal (outgoing) ubiquitin units S1 and S2 respectively. http://togogenome.org/gene/10090:Mrgprf ^@ http://purl.uniprot.org/uniprot/Q3TZA7|||http://purl.uniprot.org/uniprot/Q8VCJ6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Membrane|||Orphan receptor. May bind to a neuropeptide and may regulate nociceptor function and/or development, including the sensation or modulation of pain. http://togogenome.org/gene/10090:Tbx10 ^@ http://purl.uniprot.org/uniprot/Q810F8 ^@ Disease Annotation|||Function|||Subcellular Location Annotation ^@ Defects in Tbx10 are the cause of a cleft lip and palate (CL/P) phenotype called Dancer (Dc). The defect is caused by a gain of function.|||Nucleus|||Probable transcriptional regulator involved in developmental processes. http://togogenome.org/gene/10090:Cd209c ^@ http://purl.uniprot.org/uniprot/Q91ZW9 ^@ Caution|||Function ^@ In mouse, 5 genes homologous to human CD209/DC-SIGN and CD209L/DC-SIGNR have been identified.|||Probable pathogen-recognition receptor. May recognize in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens. http://togogenome.org/gene/10090:Slc18a3 ^@ http://purl.uniprot.org/uniprot/Q3TYJ1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pigl ^@ http://purl.uniprot.org/uniprot/Q5SX19 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGL family.|||Endoplasmic reticulum membrane|||Involved in the second step of GPI biosynthesis. De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol (By similarity). http://togogenome.org/gene/10090:Vmn1r63 ^@ http://purl.uniprot.org/uniprot/Q9EPT1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nefh ^@ http://purl.uniprot.org/uniprot/P19246|||http://purl.uniprot.org/uniprot/Q80TQ3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the sciatic nerve (at protein level).|||Forms heterodimers with NEFL; which can further hetero-oligomerize (in vitro) (By similarity). Forms heterodimers with INA (in vitro) (By similarity).|||Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. NEFH has an important function in mature axons that is not subserved by the two smaller NF proteins. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks (PubMed:22723690).|||Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.|||Phosphorylation seems to play a major role in the functioning of the larger neurofilament polypeptides (NF-M and NF-H), the levels of phosphorylation being altered developmentally and coincidentally with a change in the neurofilament function.|||There are a number of repeats of the tripeptide K-S-P, NFH is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFH results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber.|||axon|||cytoskeleton http://togogenome.org/gene/10090:Fra10ac1 ^@ http://purl.uniprot.org/uniprot/Q8BP78 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Interacts with ESS2.|||Intron retention.|||May be involved in pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Mrm2 ^@ http://purl.uniprot.org/uniprot/Q9CPY0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family.|||Mitochondrion|||S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes the formation of 2'-O-methyluridine at position 1369 (Um1369) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA. http://togogenome.org/gene/10090:Atp1b4 ^@ http://purl.uniprot.org/uniprot/B1APX1|||http://purl.uniprot.org/uniprot/Q99ME6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with a SMAD7-transcriptional complex. Interacts with TOR1AIP1. Does not associate with known Na,K-ATPase alpha-subunits (By similarity). Interacts with SNW1.|||Belongs to the X(+)/potassium ATPases subunit beta family.|||Expressed in embryo 15.5 dpc, onward.|||Expressed in skeletal muscle (at protein level). Expressed during postnatal development in skeletal muscle and heart.|||May act as a transcriptional coregulator during muscle development through its interaction with SNW1. Has lost its ancestral function as a Na,K-ATPase beta-subunit (By similarity).|||Membrane|||Nucleus inner membrane|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. http://togogenome.org/gene/10090:Chpf ^@ http://purl.uniprot.org/uniprot/Q6IQX7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Golgi stack membrane|||Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Seems to act as a specific activating factor for CHSY1 in chondroitin polymerization.|||Highest activities are measured with Mn(2+). Can also utilize Co(2+).|||Interacts with PRKN.|||Isoform 1, isoform 2 and isoform 3 are expressed in brain (at protein level).|||May facilitate PRKN transport into the mitochondria. In collaboration with PRKN, may enhance cell viability and protect cells from oxidative stress.|||Mitochondrion|||Mitochondrion matrix|||cytosol http://togogenome.org/gene/10090:S100a8 ^@ http://purl.uniprot.org/uniprot/P27005|||http://purl.uniprot.org/uniprot/Q53X15 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Upon infection by murine coronavirus (MHV-A59), induces expansion of aberrant immature neutrophils in a TLR4-dependent manner.|||Belongs to the S-100 family.|||Binds two calcium ions per molecule with an affinity similar to that of the S-100 proteins.|||Calprotectin (S100A8/A9) activity on TLR4 signaling is inhibited by paquinimod.|||Cell membrane|||Cytoplasm|||Death at an early embryonic stage due to embryo resorption, starting about 8 days after fertilization.|||Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. S100A8 and calprotectin (S100A8/9) interact with NCF2/P67PHOX, RAC1 and RAC2. Calprotectin (S100A8/9) interacts with CYBA and CYBB (By similarity). S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex (By similarity).|||S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. The iNOS-S100A8/A9 transnitrosylase complex is proposed to direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as GAPDH, ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity (By similarity).|||Secreted|||cytoskeleton http://togogenome.org/gene/10090:Furin ^@ http://purl.uniprot.org/uniprot/P23188 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S8 family. Furin subfamily.|||Binds 3 calcium ions per subunit.|||Cell membrane|||Conditional knockout in pancreas causes mild glucose intolerance (PubMed:18713856). Insulin secretion by islets of Langerhans cells is reduced (PubMed:18713856). In islets of Langerhans cells, processing of pro-proteins including Pcsk2, Ins2/proinsulin II and Gcg/proglucagon and acidification of dense-core secretory granules are reduced (PubMed:18713856). Islets of Langerhans are normal (PubMed:18713856).|||Contains a cytoplasmic domain responsible for its TGN localization and recycling from the cell surface.|||Endosome membrane|||Inhibited by the not secondly cleaved propeptide. Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148). Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK). Inhibited by heparin/heparan sulfate-binding.|||Interacts with FLNA (PubMed:9412467). Binds to PACS1 which mediates TGN localization and connection to clathrin adapters (By similarity).|||Phosphorylation is required for TGN localization of the endoprotease. In vivo, exists as di-, mono- and non-phosphorylated forms.|||Secreted|||Seems to be expressed ubiquitously (PubMed:2266110). Expressed in islets of Langerhans (PubMed:18713856).|||The inhibition peptide, which plays the role of an intramolecular chaperone, is autocatalytically removed in the endoplasmic reticulum (ER) and remains non-covalently bound to furin as a potent autoinhibitor. Following transport to the trans Golgi, a second cleavage within the inhibition propeptide results in propeptide dissociation and furin activation.|||Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:18713856). Mediates processing of TGFB1, an essential step in TGF-beta-1 activation (By similarity). Converts through proteolytic cleavage the non-functional Brain natriuretic factor prohormone into its active hormone BNP(1-45) (By similarity). By mediating processing of accessory subunit ATP6AP1/Ac45 of the V-ATPase, regulates the acidification of dense-core secretory granules in islets of Langerhans cells (PubMed:18713856).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Cnga2 ^@ http://purl.uniprot.org/uniprot/A3KGE1|||http://purl.uniprot.org/uniprot/Q62398 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA2 subfamily.|||Heterotetramer composed of two subunits of CNGA2, one of CNGA4 and one of CNGB1b. The complex forms the cyclic nucleotide-gated (CNG) channel of olfactory sensory neurons (By similarity).|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Membrane|||Odorant signal transduction is probably mediated by a G-protein coupled cascade using cAMP as second messenger. The olfactory channel can be shown to be activated by cyclic nucleotides which leads to a depolarization of olfactory sensory neurons.|||The C-terminal coiled-coil domain mediates trimerization of CNGA subunits. http://togogenome.org/gene/10090:Tmed3 ^@ http://purl.uniprot.org/uniprot/Q78IS1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMP24/GP25L family.|||COPI-coated vesicle membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi stack membrane|||Monomer in endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and cis-Golgi network. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED3; however, there are conflicting reports on the interaction. Interacts with GORASP1 and GORASP2 (By similarity).|||Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Fgfrl1 ^@ http://purl.uniprot.org/uniprot/Q91V87 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||First detected at embryonic day 7 and became clearly visible at day 11 and increased until day 17.|||Has a negative effect on cell proliferation.|||Highly expressed in the kidney, brain and lung. Weakly expressed in the muscle, thymus, lymph node, stomach, intestine, colon and liver. Expressed in fetal cartilaginous structures like the nasal cartilage, the ribs and the sternum as well as in the cartilaginous rudiments of developing bones such as the vertebrae and the pelvic bone. High expression is found in the muscles of the tongue and the diaphragm.|||Interacts with FGF2 with a low affinity. http://togogenome.org/gene/10090:Vmn1r173 ^@ http://purl.uniprot.org/uniprot/E9Q8V7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Map3k9 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VKX4|||http://purl.uniprot.org/uniprot/Q3U1V8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-305 is likely to be the main autophosphorylation site (By similarity). Autophosphorylation also occurs on Thr-297 and Ser-301 (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Expressed in cochlea and utricle.|||Homodimer.|||Homodimerization via the leucine zipper domains is required for autophosphorylation of multiple sites in the activation loop and subsequent activation. Autophosphorylation at Thr-305 is the key step in activation of MAP3K9/MLK1 and is required for full phosphorylation. Autophosphorylation at Thr-297 and Ser-301 have been shown to be of secondary importance in the activation of MAP3K9/MLK1.|||Homodimerization via the leucine zipper domains is required for autophosphorylation.|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Also plays a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis (By similarity). http://togogenome.org/gene/10090:3830406C13Rik ^@ http://purl.uniprot.org/uniprot/Q8BGD0 ^@ Function|||Subcellular Location Annotation ^@ May play a role in ciliary assembly.|||cilium http://togogenome.org/gene/10090:Neo1 ^@ http://purl.uniprot.org/uniprot/E9QK04|||http://purl.uniprot.org/uniprot/P97798|||http://purl.uniprot.org/uniprot/Q7TQG5 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. DCC family.|||Cell membrane|||Expressed ubiquitously throughout the mid to late stages of gestation and in adult tissues. Strong expression is observed in the ventral region of the ventricular zone of the 15.5 dpc mouse neural tube, as well as in the ventricular zones of the mesencephalon and rhombencephalon. Isoform 3 and isoform 4 are expressed at higher level compared to other isoforms between 11.5 dpc and 16.5 dpc.|||Expression developmentally regulated.|||Interacts with BMP2, BMP4, BMP6, and BMP7 (By similarity). Interacts with RGMA and RGMB. Interacts with MYO10.|||Membrane|||Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Receptor for members of the BMP, netrin, and repulsive guidance molecule (RGM) families. Netrin-Neogenin interactions result in a chemoattractive axon guidance response and cell-cell adhesion, the interaction between NEO1/Neogenin and RGMa and RGMb induces a chemorepulsive response.|||The Fibronectin repeats 5 and 6 mediate interaction with RGM family molecules.|||Widely expressed. http://togogenome.org/gene/10090:Sirt6 ^@ http://purl.uniprot.org/uniprot/P59941 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-33 (By similarity). Deacetylation at Lys-33 by SIRT1 promotes homomultimerization and binding to double-strand breaks (DSBs) sites (By similarity).|||Belongs to the sirtuin family. Class IV subfamily.|||Binds 1 zinc ion per subunit.|||By cold (PubMed:28723567). In hepatocytes, expression is increased following incubation in a ketonic medium (PubMed:30530497).|||Chromosome|||Compared to beaver, mouse SIRT6 displays lower histone deacetylase activity and ability to promote double-strand break (DSB) repair, possibly leading to shorter life span.|||Compared to the defatty-acylase activity, the protein deacetylase activity is weak in vitro, and requires activation (By similarity). The histone deacetylase activity is strongly activated upon binding to nucleosomes and chromatin in vivo (By similarity). Two molecules of SIRT6 associate with the acidic patch of one nucleosome, while the C-terminal disordered region of SIRT6 associates with nucleosomal DNA, leading to efficient histone deacetylation (By similarity). The protein-lysine deacetylase activity is also activated by long-chain free fatty-acids (By similarity).|||Endoplasmic reticulum|||Expression peaks at embryonic day 11 and persists into adulthood.|||Highest levels are found in muscle, thymus, spleen, brain and heart (at protein level).|||Homodimer; binds to nucleosomes and DNA ends as a homodimer (By similarity). Interacts with RELA; interferes with RELA binding to target DNA (PubMed:19135889). Interacts with SMARCA5; promoting recruitment of SMARCA5/SNF2H to double-strand breaks (DSBs) sites (By similarity). Interacts with the mTORC2 complex; preventing the ability of SIRT6 to deacetylate FOXO1 (PubMed:31442424). Interacts with the CLOCK-BMAL1 complex; recruited by the CLOCK-BMAL1 complex to regulate expression of clock-controlled genes (PubMed:25083875). Interacts with CSNK2A2; preventing CSNK2A2 localization to the nucleus (PubMed:28355567).|||Mice display multiple defects, accelerated aging and die a few weeks after birth, because of impaired genomic stability (PubMed:16439206). Mice do not show any visible phenotype at birth and undergo a normal development during the first two weeks, except for reduced growth (PubMed:16439206). By two/three weeks of age, mice in a 129/SvJ background display severe metabolic defects and develop abnormalities usually associated with aging (PubMed:16439206, PubMed:20847051). These include acute loss of subcutaneous fat, lordokyphosis, erosion of the superficial colon epithelium, severe lymphopenia, osteopenia and severely reduced IGF1 serum levels (PubMed:16439206). Severe hypoglycemia, characterized by very low levels of blood glucose, is also observed (PubMed:16439206, PubMed:20847051). Mice also show defects in DNA double-strand break (DSB) repair (PubMed:23911928, PubMed:32538779). Derepression of LINE-1 retrotransposon elements is also observed, leading to an accumulation of cytoplasmic L1 cDNAs, which triggers the cGAS-STING pathway, driving inflammation (PubMed:30853213). Mice die about 24 days after birth (PubMed:16439206). Mice in a mixed 129/SvJ and BALB/c background reach adulthood: at 200 days of age, more than 80% of the female mice survive whereas only 10% of male mice are alive (PubMed:28448551). Mutant mice in this mixed background (129/SvJ and BALB/c) display reduced body weight, increased glucose uptake and exhibit an age-dependent progressive impairment of retinal function accompanied by thinning of retinal layers (PubMed:28448551). Sirt6-deficient mice that are haploinsufficient with p53/Tp53 display a strongly extended life span in both females and males (PubMed:29474172). Conditional deletion in the liver leads to increased glycolysis, fatty liver, triglyceride synthesis and reduced beta-oxidation (PubMed:20816089). Conditional deletion in the liver also leads to elevated LDL-cholesterol levels (PubMed:23974119). Conditional deletion in hepatocytes leads to impaired ketogenesis (PubMed:30530497). Conditional deletion in adipocytes promotes high-fat diet-induced obesity because of impaired lipolytic activity (PubMed:28723567, PubMed:28250020). Conditional deletion in pancretic beta-cells leads to glucose intolerance with severely impaired glucose-stimulated insulin secretion (PubMed:27457971). Conditional deletion in neurons leads to postnatal growth retardation and obesity (PubMed:21098266). Conditional deletion in podocytes exacerbates podocyte injury and proteinuria; defects are caused by derepression of the Notch signaling (PubMed:28871079).|||Monoubiquitinated at Lys-170 by STUB1/CHIP, preventing its degradation by the proteasome.|||NAD-dependent protein deacetylase, deacylase and mono-ADP-ribosyltransferase that plays an essential role in DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis and aging (PubMed:16439206, PubMed:19135889, PubMed:20141841, PubMed:19220062, PubMed:19597350, PubMed:23217706, PubMed:23911928, PubMed:27180906, PubMed:29599436). Displays protein-lysine deacetylase or defatty-acylase (demyristoylase and depalmitoylase) activity, depending on the context (By similarity). Acts as a key histone deacetylase by catalyzing deacetylation of histone H3 at 'Lys-9', 'Lys-18' and 'Lys-56' (H3K9ac, H3K18ac and H3K56ac, respectively), suppressing target gene expression of several transcription factors, including NF-kappa-B (PubMed:19135889, PubMed:19597350, PubMed:20816089, PubMed:21098266, PubMed:25915124, PubMed:28871079, PubMed:31002797, PubMed:31399344). Acts as an inhibitor of transcription elongation by mediating deacetylation of H3K9ac and H3K56ac, preventing release of NELFE from chromatin and causing transcriptional pausing (PubMed:31399344). Involved in DNA repair by promoting double-strand break (DSB) repair: acts as a DSB sensor by recognizing and binding DSB sites, leading to (1) recruitment of DNA repair proteins, such as SMARCA5/SNF2H, and (2) deacetylation of histone H3K9ac and H3K56ac (PubMed:32538779). SIRT6 participation to DSB repair is probably involved in extension of life span (PubMed:22367546, PubMed:31002797). Also promotes DNA repair by deacetylating non-histone proteins, such as DDB2 and p53/TP53 (By similarity). Specifically deacetylates H3K18ac at pericentric heterochromatin, thereby maintaining pericentric heterochromatin silencing at centromeres and protecting against genomic instability and cellular senescence (By similarity). Involved in telomere maintenance by catalyzing deacetylation of histone H3 in telomeric chromatin, regulating telomere position effect and telomere movement in response to DNA damage (PubMed:29599436). Required for embryonic stem cell differentiation by mediating histone deacetylation of H3K9ac (PubMed:25915124, PubMed:29555651). Plays a major role in metabolism by regulating processes such as glycolysis, gluconeogenesis, insulin secretion and lipid metabolism (PubMed:20141841, PubMed:20816089, PubMed:20847051, PubMed:21098266, PubMed:23974119, PubMed:27457971, PubMed:28355567, PubMed:28250020, PubMed:34050173). Inhibits glycolysis via histone deacetylase activity and by acting as a corepressor of the transcription factor HIF1A, thereby controlling the expression of multiple glycolytic genes (PubMed:20141841). Has tumor suppressor activity by repressing glycolysis, thereby inhibiting the Warburg effect (PubMed:23217706). Also regulates glycolysis and tumorigenesis by mediating deacetylation and nuclear export of non-histone proteins, such as isoform M2 of PKM (PKM2) (By similarity). Acts as a negative regulator of gluconeogenesis by mediating deacetylation of non-histone proteins, such as FOXO1 and KAT2A/GCN5 (PubMed:23142079, PubMed:25009184). Promotes beta-oxidation of fatty acids during fasting by catalyzing deacetylation of NCOA2, inducing coactivation of PPARA (PubMed:31851938). Acts as a regulator of lipid catabolism in brown adipocytes, both by catalyzing deacetylation of histones and non-histone proteins, such as FOXO1 (PubMed:28723567, PubMed:31442424). Also acts as a regulator of circadian rhythms, both by regulating expression of clock-controlled genes involved in lipid and carbohydrate metabolism, and by catalyzing deacetylation of PER2 (PubMed:25083875, PubMed:30782483). The defatty-acylase activity is specifically involved in regulation of protein secretion (PubMed:19151729, PubMed:27322069). Has high activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as RRAS2 and TNF, thereby regulating their secretion (By similarity). Also acts as a mono-ADP-ribosyltransferase by mediating mono-ADP-ribosylation of PARP1, TRIM28/KAP1 or SMARCC2/BAF170 (PubMed:15795229, PubMed:21680843, PubMed:25247314, PubMed:31216030). Mono-ADP-ribosyltransferase activity is involved in DNA repair, cellular senescence, repression of LINE-1 retrotransposon elements and regulation of transcription (PubMed:21680843, PubMed:25247314, PubMed:30853213, PubMed:31216030, PubMed:32584788).|||Nucleus|||Phosphorylation at Ser-10 by MAPK8/JNK1 in response to oxidative stress stimulates the mono-ADP-ribosyltransferase activity on PARP1, leading to PARP1 recruitment to double-strand breaks (DSBs).|||Sumoylated, leading to specifically decrease ability to deacetylate histone H3 at 'Lys-56' (H3K56ac).|||The C-terminal disordered region mediates non-specific DNA-binding.|||telomere http://togogenome.org/gene/10090:Bet1l ^@ http://purl.uniprot.org/uniprot/O35153 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of a SNARE complex consisting of STX5, YKT6, GOSR2 and BET1L.|||Golgi apparatus membrane|||Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex. Required for the integrity of the Golgi complex (By similarity).|||trans-Golgi network membrane http://togogenome.org/gene/10090:H4c11 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Tex13b ^@ http://purl.uniprot.org/uniprot/Q99MW5 ^@ Similarity ^@ Belongs to the TEX13 family. http://togogenome.org/gene/10090:Osbpl5 ^@ http://purl.uniprot.org/uniprot/G5E833|||http://purl.uniprot.org/uniprot/Q9ER64 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the OSBP family.|||Endoplasmic reticulum membrane|||Imprinted gene expressed from the maternal allele in blastocysts.|||Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner. May cooperate with NPC1 to mediate the exit of cholesterol from endosomes/lysosomes. Binds 25-hydroxycholesterol and cholesterol. http://togogenome.org/gene/10090:Zbtb24 ^@ http://purl.uniprot.org/uniprot/Q80X44 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||By BMP2 in fibroblast, myoblast and preosteoblast cell lines.|||Interacts with MN1.|||May be involved in BMP2-induced transcription.|||Nucleus|||Widely expressed. Highest level in liver, testis and kidney. http://togogenome.org/gene/10090:Lrif1 ^@ http://purl.uniprot.org/uniprot/Q8CDD9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LRIF1 family.|||Chromosome|||Interacts with RARA (By similarity). Interacts with SMCHD1; leading to recruitment to inactivated chromosome X in females (PubMed:26391951). Interacts (via PxVxL motif) with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha) (By similarity).|||Nucleus matrix|||The Pro-Xaa-Val-Xaa-Leu (PxVxL) motif mediates interaction with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha).|||Together with SMCHD1, involved in chromosome X inactivation in females by promoting the compaction of heterochromatin. Also able to repress the ligand-induced transcriptional activity of retinoic acid receptor alpha (RARA), possibly through direct recruitment of histone deacetylases. http://togogenome.org/gene/10090:Pkn1 ^@ http://purl.uniprot.org/uniprot/P70268 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by limited proteolysis with trypsin.|||Autophosphorylated; preferably on serine.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Cell membrane|||Cleavage furrow|||Cytoplasm|||Endosome|||Interacts with ZFAND6 (PubMed:11054541). Interacts with ANDR. Interacts with PRKCB. Interacts (via REM 1 and REM 2 repeats) with RAC1 (By similarity). Interacts (via REM 1 repeat) with RHOA (PubMed:8571127). Interacts with RHOB. Interacts (via C-terminus) with PDPK1. Interacts with CCNT2; enhances MYOD1-dependent transcription. Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (By similarity).|||Kinase activity is activated upon binding to Rho proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids. Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific sites, Thr-778 (activation loop of the kinase domain) and Ser-920 (turn motif), need to be phosphorylated for its full activation.|||Midbody|||Nucleus|||PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.|||The C1 domain does not bind the diacylglycerol (DAG). http://togogenome.org/gene/10090:Or6c69c ^@ http://purl.uniprot.org/uniprot/Q8VFU1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Clk3 ^@ http://purl.uniprot.org/uniprot/O35492 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylates on all three types of residues.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.|||Cytoplasm|||Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.|||Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.|||Nucleus|||Present at high levels in testis and ovary. In testis, expression is restricted to elongated, maturing spermatozoa. Also present in spleen, brain, lung and liver (at protein level).|||acrosome http://togogenome.org/gene/10090:Vps36 ^@ http://purl.uniprot.org/uniprot/Q3TSR1|||http://purl.uniprot.org/uniprot/Q91XD6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS36 family.|||Component of a complex at least composed of ELL, SNF8/EAP30, VPS25/EAP20 and VPS36/EAP45 (By similarity). Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS36 and two copies of VPS25 (By similarity). Interacts with VPS25, SNF8, TSG101 and CHMP6 (By similarity). Interacts (via GLUE domain) with ubiquitin (PubMed:15755741). Interacts with RILPL1 (via the C-terminal domain); which recruits ESCRT-II to the endosome membranes (By similarity). Interacts with ECPAS (By similarity).|||Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs.|||Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. Its ability to bind ubiquitin probably plays a role in endosomal sorting of ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. Binds phosphoinosides such as PtdIns(3,4,5)P3.|||Component of the endosomal sorting complex required for transport II (ESCRT-II).|||Cytoplasm|||Endosome|||Late endosome|||Membrane|||Nucleus|||The GLUE domain (GRAM-like ubiquitin-binding in EAP45) mediates binding to ubiquitin and phosphoinosides. http://togogenome.org/gene/10090:Otp ^@ http://purl.uniprot.org/uniprot/O09113 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Death at birth or within the first 2 postnatal days due to defects in neuroendocrine hypothalamus differentiation.|||First detected at 9.5 dpc in restricted domains of the developing diencephalon and along all the hindbrain and the spinal cord. At 10 dpc, found in the medioventral region of the developing spinal cord. At 12.5 dpc, expressed in restricted zones in the preoptic, postoptic and dorsoposterior regions. At later stages, in the intermedial region of the lateral horn, in the optic tract, the presumptive stria terminalis, the amygdaloid complex of the lateral horn in the spinal cord.|||Involved in the specification of hypothalamic neuroendocrine cells. Specifically required for the specification of diencephalic dopaminergic neurons of the A11 group.|||Nucleus|||Restricted regions of the developing forebrain, hindbrain, and spinal cord. http://togogenome.org/gene/10090:Zic4 ^@ http://purl.uniprot.org/uniprot/G3UYE7|||http://purl.uniprot.org/uniprot/Q61467|||http://purl.uniprot.org/uniprot/Q8C8J4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GLI C2H2-type zinc-finger protein family.|||Binds to DNA.|||Exclusively expressed in the cerebellum.|||First expressed in embryo at 9 dpc. Expressed in the dorsal midline of the forebrain at 10.5 dpc at the boundary between the diencephalon and telencephalon, the septum, and the lamina terminalis. Expressed in the choroid plexus of the third ventricle, the dorsal part of the spinal neural tube, the dorsal sclerotome and the dorsomedial lip of the dermomyotome between 10.5 and 12.5 dpc. Expressed in the midline of the forebrain and in the dorsal spinal neural tube at 12.5 dpc.|||Nucleus http://togogenome.org/gene/10090:Wwp1 ^@ http://purl.uniprot.org/uniprot/Q8BZZ3 ^@ Activity Regulation|||Domain|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Activated by NDFIP1- and NDFIP2-binding.|||Auto-ubiquitinated and ubiquitinated by RNF11.|||Binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA and adenovirus type 2 PIII. Interacts with TGIF (By similarity). Binds KLF2 AND HIVEP3. Interacts with RNF11. Interacts with SPART. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (By similarity). Interacts with ERBB4 isoforms JM-B CYT-1 and JM-A CYT-1. Does not interact with ERB4 isoform JMA-A CYT-2. Interacts with SMAD1, SMAD2, SMAD3, SMAD5, SMAD6, SMAD7, TGFBR1 and TGFBR2. Associates with the TGFBR1:TGFBR2 receptor complex in presence of SMAD7. Interacts with SKIL isoform 1. Interacts with TP63 isoform 1 and isoform 2. Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3 (By similarity).|||Cell membrane|||Chimera. The second part of the clone maps to another chromosome.|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF (By similarity). Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7.|||Nucleus|||The WW domains mediate interaction with PPxY motif-containing proteins. http://togogenome.org/gene/10090:Chn1 ^@ http://purl.uniprot.org/uniprot/Q91V57 ^@ Disruption Phenotype|||Function|||PTM|||Subunit ^@ GTPase-activating protein for p21-rac and a phorbol ester receptor. May play an important role in neuronal signal-transduction mechanisms (By similarity). Involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance.|||Interacts with EPHA4; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation. May also interact with EPHB1 and EPHB2.|||Mice are viable and fertile but display a loss of coordination of limb movement which phenocopies the one of Epha4 mutant mice.|||Phosphorylated. Phosphorylation is EPHA4 kinase activity-dependent. http://togogenome.org/gene/10090:Cbx4 ^@ http://purl.uniprot.org/uniprot/O55187 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (By similarity). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (By similarity). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) (PubMed:16537902). Plays a role in the lineage differentiation of the germ layers in embryonic development (PubMed:22226355).|||E3 SUMO-protein ligase which facilitates SUMO1 conjugation by UBE2I. Involved in the sumoylation of HNRNPK, a p53/TP53 transcriptional coactivator, hence indirectly regulates p53/TP53 transcriptional activation resulting in p21/CDKN1A expression.|||Expressed in embryoid bodies.|||Interacts with SUV39H1 and HIPK2 (By similarity). Interacts with CSNK2B (By similarity). Component of a PRC1-like complex (By similarity). The composition of the PRC1 complex differs between the PRC1 complex in pluripotent embryonic stem cells containing RNF2, CBX7 and PCGF2, and the PRC1 complex in differentiating cells containing RNF2, CBX2, CBX4 and BMI1 (PubMed:22226355). Interacts with RNF2 (PubMed:22226355). Interacts (via chromodomain) with histone H3K9Me3 and single-stranded RNA (ssRNA) (PubMed:16537902). Interacts with CHTOP (PubMed:22872859). May interact with H3C15 and H3C1 (By similarity). Interacts with PRDM1 (By similarity).|||Nucleus|||Nucleus speckle|||The polyhistidine repeat may act as a targeting signal to nuclear speckles.|||Ubiquitinated. Ubiquitination regulates the function of the Polycomb group (PcG) multiprotein PRC1-like complex. Deubiquitinated by USP26. http://togogenome.org/gene/10090:Kdm3b ^@ http://purl.uniprot.org/uniprot/Q6ZPY7 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the JHDM2 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate May have tumor suppressor activity (By similarity).|||Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.|||Nucleus http://togogenome.org/gene/10090:Pemt ^@ http://purl.uniprot.org/uniprot/Q61907 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class VI-like SAM-binding methyltransferase superfamily. PEMT/PEM2 methyltransferase family.|||Catalyzes the three sequential steps of the methylation pathway for the biosynthesis of phosphatidylcholine, a critical and essential component for membrane structure (PubMed:9371769) (Probable). Uses S-adenosylmethionine (S-adenosyl-L-methionine, SAM or AdoMet) as the methyl group donor for the methylation of phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE) to phosphatidylmonomethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine, PMME), PMME to phosphatidyldimethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine, PDME), and PDME to phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), producing S-adenosyl-L-homocysteine in each step (PubMed:9371769).|||Endoplasmic reticulum membrane|||Expressed in liver (at protein level).|||Mitochondrion membrane|||Severe liver pathology rapidly occurs in knockout mice after 3-days withdrawal of dietary choline, which might occur during starvation, pregnancy or lactation, and may die after 4-5 days (PubMed:9765216). Homocysteine plasma content in knockouts is 50 percent less of the content in wild type mice (PubMed:12482759). http://togogenome.org/gene/10090:Rhox3a ^@ http://purl.uniprot.org/uniprot/Q4TU90 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Cmtm3 ^@ http://purl.uniprot.org/uniprot/Q99LJ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chemokine-like factor family.|||Membrane http://togogenome.org/gene/10090:Hsfy2 ^@ http://purl.uniprot.org/uniprot/Q80Y37 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the HSF family.|||Nucleus http://togogenome.org/gene/10090:Zscan4c ^@ http://purl.uniprot.org/uniprot/Q80VJ6 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Embryonic stem (ES) cell-specific transcription factor required to regulate ES cell pluripotency. Binds telomeres and plays a key role in genomic stability in ES cells by regulating telomere elongation. Acts as an activator of spontaneous telomere sister chromatid exchange (T-SCE) and telomere elongation in undifferentiated ES cells.|||Embryonic stem (ES) cell-specific. Expressed in only 5% of ES cells at a given time, but nearly all ES cells express it at least once during 9 passages.|||Nucleus|||Transcriptionally regulated by ZSCAN10.|||telomere http://togogenome.org/gene/10090:Grpel1 ^@ http://purl.uniprot.org/uniprot/Q99LP6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GrpE family.|||Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins (By similarity).|||Mitochondrion matrix|||Probable component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19. Binds to HSP70, HSC70 and HSJ1B (By similarity). http://togogenome.org/gene/10090:Prdm8 ^@ http://purl.uniprot.org/uniprot/Q8BZ97 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Expressed in brain, heart, liver, testes, retina (PubMed:19646955, PubMed:22284184). Highest expression is observed in the retina and hippocampus; moderately expressed in the cortex and cerebellum. In the retina, it is expressed in bipolar and amacrine cells (PubMed:26023183).|||Interacts with BHLHE22 (PubMed:22284184). Interacts with EPM2A and NHLRC1. This interaction sequesters EPM2A and NHLRC1 to the nucleus (By similarity).|||Knockout mice lacking PRDM8 shows absence of the corticospinal tract, agenesis of the corpus callosum and hippocampal commissure; they have an abnormal itching behavior that results in the formation of skin lesions, and occasionally display an unusual movement in which they walk on their forepaws (PubMed:22284184). PRDM8-null mice also have a non-progressive defect in retinal responses, and loss of rod bipolar and type 2 OFF-cone bipolar cells (PubMed:26023183).|||Nucleus|||Probable histone methyltransferase, preferentially acting on 'Lys-9' of histone H3 (PubMed:19646955). Histone methyltransferase activity has not been confirmed in other species. Involved in the control of steroidogenesis through transcriptional repression of steroidogenesis marker genes such as CYP17A1 and LHCGR (PubMed:19646955). Forms with BHLHE22 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation (PubMed:22284184). In the retina, it is required for rod bipolar and type 2 OFF-cone bipolar cell survival (PubMed:26023183). http://togogenome.org/gene/10090:Or7g22 ^@ http://purl.uniprot.org/uniprot/Q8VFJ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Neurog1 ^@ http://purl.uniprot.org/uniprot/P70660 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis.|||Efficient DNA binding requires dimerization with another bHLH protein.|||Expression restricted to the embryonic nervous system.|||Highest expression in the embryo between days 10 and 12. Declines to undetectable levels by embryonic day 16.|||Nucleus http://togogenome.org/gene/10090:Or4c112 ^@ http://purl.uniprot.org/uniprot/Q8VGG1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mtus1 ^@ http://purl.uniprot.org/uniprot/Q5HZI1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MTUS1 family.|||Cell membrane|||Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation.|||Golgi apparatus|||Homodimer. Interacts with AGTR2. Interacts with PTPN6.|||Mitochondrion|||Nucleus|||Ubiquitously expressed, with highest levels in uterus and adrenal gland. http://togogenome.org/gene/10090:Smim13 ^@ http://purl.uniprot.org/uniprot/E9Q942 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMIM13 family.|||Membrane http://togogenome.org/gene/10090:Hnf1a ^@ http://purl.uniprot.org/uniprot/P22361|||http://purl.uniprot.org/uniprot/Q66JY7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HNF1 homeobox family.|||Binds DNA as a dimer (PubMed:11106484, PubMed:11439029). Heterotetramer with PCBD1; formed by a dimer of dimers (PubMed:10966642). Interacts with PCBD1 (By similarity). Interacts with BHLHE41 (PubMed:30555544).|||Liver.|||Mice are born at less than half of the expected frequency. Neonates are slightly smaller than normal and do not grow normally. After 5 weeks mice weigh only 50 to 60% as much as their littermates. Mice develop non-insulin-dependent diabetes mellitus (NIDDM) 2 weeks after birth. Mice exhibit elevated levels of blood glucose, combined with reduced blood levels of insulin and insulin-like growth factor I (IGFI). Males and females are sterile.|||Nucleus|||Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (PubMed:19289501). Binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:10966642). Activates the transcription of CYP1A2, CYP2E1 and CYP3A11 (PubMed:30555544). http://togogenome.org/gene/10090:Sesn3 ^@ http://purl.uniprot.org/uniprot/A2RSF4|||http://purl.uniprot.org/uniprot/Q9CYP7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sestrin family.|||Cytoplasm|||Detected in liver and skeletal muscles.|||Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is not regulated by leucine (By similarity). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). Interacts with the TORC2 complex; through RICTOR (PubMed:25377878).|||Liver-specific Sesn3 knockout mice display insulin resistance and glucose intolerance (PubMed:25377878). Sesn2 and Sesn3 double knockout mice display insulin resistance and glucose intolerance (PubMed:22958918). Triple knockout mice lacking Sesn1, Sesn2 and Sesn3 do not display an embryonic lethal phenotype since they are born at an expected Mendelian ratio. Moreover, they are not distinguishable from their wild-type littermate. However, their survival at 10 days is dramatically affected. This is associated with a constitutive activation of TORC1 signaling in the liver, heart and skeletal muscle during postnatal fasting, that occurs between birth and suckling (PubMed:25259925).|||May function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway (PubMed:25259925). May also regulate the insulin-receptor signaling pathway through activation of TORC2 (PubMed:25377878). This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses (By similarity). May prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity).|||The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.|||The N-terminal domain may have an alkylhydroperoxide reductase activity. http://togogenome.org/gene/10090:Sult2a3 ^@ http://purl.uniprot.org/uniprot/D3Z1W5 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Bmp6 ^@ http://purl.uniprot.org/uniprot/P20722|||http://purl.uniprot.org/uniprot/Q3UXB2|||http://purl.uniprot.org/uniprot/Q8BRW3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Deficient mice are viable and fertile without displaying overt effects in tissues known to express BMP6, suggesting a functional redundancy among the factors of this subgroup (PubMed:9664685). However, these mice show a significant increased liver iron content (PubMed:19252486, PubMed:32464486).|||Expressed in the lung. Low levels seen in the kidney.|||Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation (By similarity). Also plays an important role in the regulation of HAMP/hepcidin expression and iron metabolism by acting as a ligand for hemojuvelin/HJV (PubMed:19252486). Also acts to promote expression of HAMP, potentially via the interaction with its receptor BMPR1A/ALK3 (PubMed:31800957). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2B. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target. Can also signal through non-canonical pathway such as TAZ-Hippo signaling cascade to modulate VEGF signaling by regulating VEGFR2 expression (By similarity).|||Interacts with SOSTDC1 (PubMed:14623234). Interacts (when glycosylated) with type I receptor ACVR1; the interaction may induce HAMP expression (PubMed:31800957). Interacts with type II receptor ACVR2B (By similarity). Interacts with Hemojuvelin/HJV (PubMed:19252486). Interacts with ERFE; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509, PubMed:31800957). Interacts with BMPR1A/ALK3 (PubMed:31800957). Forms heterodimers with BMP2 in vitro; the heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression (PubMed:31800957).|||Secreted http://togogenome.org/gene/10090:Vmn1r175 ^@ http://purl.uniprot.org/uniprot/K7N6T9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sap25 ^@ http://purl.uniprot.org/uniprot/Q1EHW4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Involved in the transcriptional repression mediated by the mSIN3A but not the N-CoR corepressor complex.|||May be a component of the mSIN3A corepressor complex. Interacts with SIN3A and HDAC2.|||Nucleus|||Widely expressed. http://togogenome.org/gene/10090:C1galt1 ^@ http://purl.uniprot.org/uniprot/Q9JJ06 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family. Beta3-Gal-T subfamily.|||Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins. Plays a central role in many processes, such as angiogenesis, thrombopoiesis and kidney homeostasis development.|||Homodimer; disulfide-linked. Interacts with the C1GALT1C1 chaperone; required for galactosyltransferase activity (By similarity).|||Membrane|||Mice develop brain hemorrhage that cause death at 14 dpc during development. They express the nonsialylated Tn antigen and brains form a chaotic microvascular network with distorted capillary lumens and defective association of endothelial cells with pericytes and extracellular matrix.|||Primarily expressed in endothelial, hematopoietic and epithelial cells during development. http://togogenome.org/gene/10090:Mip ^@ http://purl.uniprot.org/uniprot/P51180 ^@ Caution|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side (By similarity).|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Defects in Mip are a cause of autosomal dominant cataract. The cataract Fraser mutation (Cat-Fr or Shrivelled) is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the C-terminus of Mip. The lens opacity mutation (LOP) is an AA substitution that inhibits targeting of Mip to the cell-membrane.|||Fatty acylated at Met-1 and Lys-238. The acyl modifications, in decreasing order of ion abundance, are: oleoyl (C18:1) > palmitoyl (C16:0) > stearoyl (C18:0) > eicosenoyl (C20:1) > dihomo-gamma-linolenoyl (C20:3) > palmitoleoyl (C16:1) > eicosadienoyl (C20:2).|||Homotetramer. Homooctamer formed by head-to-head interaction between homotetramers from adjoining membranes. Interacts with CALM; one CALM molecule interacts with the cytoplasmic domains of two aquaporins, leading to channel closure. Interacts (via C-terminus) with BFSP1 (via C-terminus) in aged lens fiber cells (By similarity).|||Major component of lens fiber gap junctions.|||Ref.2 sequence was originally thought to originate from Human.|||Subject to partial proteolytic cleavage in the eye lens core. Partial proteolysis promotes interactions between tetramers from adjoining membranes (By similarity).|||Water channel. Channel activity is down-regulated by CALM when cytoplasmic Ca(2+) levels are increased. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core. Plays a role in cell-to-cell adhesion and facilitates gap junction coupling (By similarity).|||gap junction http://togogenome.org/gene/10090:Or8b50 ^@ http://purl.uniprot.org/uniprot/E9PW59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Baiap2 ^@ http://purl.uniprot.org/uniprot/B1AZ46|||http://purl.uniprot.org/uniprot/Q3UKP6|||http://purl.uniprot.org/uniprot/Q8BKX1 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions.|||Cytoplasm|||Detected in liver, brain, olfactory bulb, brain cortex, caudate putamen, hypothalamus and cerebellum.|||Homodimer. Interacts with CDC42 and RAC1 that have been activated by GTP binding. Binds DIAPH1. Interacts with ATN1, ADGRB1, SHANK1, SHANK2, SHANK3, TIAM1, WASF1 and WASF2. Interacts with ENAH after recruitment of CDC42 (By similarity). Interacts with EPS8.|||Membrane|||Phosphorylated on tyrosine residues by INSR in response to insulin treatment.|||The IMD domain forms a coiled coil. The isolated domain can induce actin bundling and filopodia formation. In the absence of G-proteins intramolecular interaction between the IMD and the SH3 domain gives rise to an auto-inhibited state of the protein. Interaction of the IMD with RAC1 or CDC42 leads to activation (By similarity).|||The SH3 domain interacts with ATN1, ADGRB1, WASF1, WASF2, SHANK1, DIAPH1 and ENAH.|||cytoskeleton|||filopodium|||ruffle http://togogenome.org/gene/10090:Saxo2 ^@ http://purl.uniprot.org/uniprot/Q8BQB6 ^@ Similarity ^@ Belongs to the FAM154 family. http://togogenome.org/gene/10090:Mal ^@ http://purl.uniprot.org/uniprot/O09198 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abnormal myelination and optic nerve morphology.|||Apical cell membrane|||Belongs to the MAL family.|||Could be an important component in vesicular trafficking cycling between the Golgi complex and the apical plasma membrane. Plays a role in the maintenance of the myelin sheath and in axon-glia and glia-glia interactions.|||Expressed in the spinal cord, brain, kidney and gastrointestinal tract especially in the stomach and caecum. Highly expressed by myelinating glial cells.|||Golgi apparatus membrane|||Lipoprotein. http://togogenome.org/gene/10090:Hspa5 ^@ http://purl.uniprot.org/uniprot/P20029|||http://purl.uniprot.org/uniprot/Q3U7T8 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||Cell surface|||Cytoplasm|||Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:12411443, PubMed:12475965). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (PubMed:12411443). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (By similarity).|||Endoplasmic reticulum lumen|||Expressed in sperm (at protein level).|||In unstressed cells, AMPylation at Thr-519 by FICD inactivates the chaperome activity: AMPylated form is locked in a relatively inert state and only weakly stimulated by J domain-containing proteins. In response to endoplasmic reticulum stress, de-AMPylation by the same protein, FICD, restores the chaperone activity.|||Induced in sinus, lung and brain tissue in response to 3-hydroxybutyric acid (BHB)-induced acidosis (PubMed:27159390). Induced in sinus, lung and brain tissue following intraperitoneal injection of streptozotocin to produce a mouse model of diabetic ketoacidosis (DKA) (PubMed:20484814).|||Melanosome|||Monomer and homooligomer; homooligomerization via the interdomain linker inactivates the chaperone activity and acts as a storage of HSPA5/BiP molecules (By similarity). Interacts with DNAJC1 (via J domain) (PubMed:12065409). Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (PubMed:16931514). Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX (PubMed:12475965). Interacts with TMEM132A and TRIM21 (By similarity). May form a complex with ERLEC1, OS9, SEL1L and SYVN1 (By similarity). Interacts with DNAJC10 (PubMed:12411443). Interacts with DNAJB9/ERdj4; leading to recruit HSPA5/BiP to ERN1/IRE1 (PubMed:11836248). Interacts with ERN1/IRE1; interaction takes place following interaction with DNAJB9/ERdj4 and leads to inactivate ERN1/IRE1 (By similarity). Interacts with MX1 (PubMed:21992152). Interacts with METTL23 (By similarity). Interacts with CEMIP; the interaction induces calcium leakage from the endoplasmic reticulum and cell migration (By similarity). Interacts with PCSK4 form; the interaction takes place in the endoplasmic reticulum (By similarity). Interacts with CIPC (By similarity). Interacts with CCDC88B (via C-terminus); the interaction opposes ERN1-mediated JNK activation, protecting against apoptosis (By similarity). Interacts with INPP5K; necessary for INPP5K localization at the endoplasmic reticulum (By similarity). Interacts with MANF; the interaction is direct (By similarity). Interacts with LOXL2; leading to activate the ERN1/IRE1-XBP1 pathway of the unfolded protein response (By similarity). Interacts with CLU under stressed condition; interaction increases CLU protein stability; facilitates its retrotranslocation and redistribution to the mitochondria; cooperatively suppress stress-induced apoptosis by stabilizing mitochondrial membrane integrity (By similarity). Interacts with CCDC47 (PubMed:25009997). Interacts with CLN3 (By similarity). Interacts with KIAA1324; may regulate the function of HSPA5 in apoptosis and cell proliferation. Interacts with CASP7 (By similarity). Interacts with ILDR2; the interaction stabilizes ILDR2 expression (PubMed:33863978). Interacts with ADAM7 (PubMed:20945367).|||The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP. Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (By similarity).|||The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one HSPA5/BiP molecule as a typical substrate of an adjacent HSPA5/BiP molecule. HSPA5/BiP oligomerization inactivates participating HSPA5/BiP protomers. HSPA5/BiP oligomers probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers. http://togogenome.org/gene/10090:Slc5a9 ^@ http://purl.uniprot.org/uniprot/Q8VDT1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Electrogenic Na(+)-coupled sugar symporter that may play a primary role in D-mannose and possibly D-fructose and D-glucose transport at the plasma membrane. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Exclusively recognizes sugar substrates having a pyranose ring with an axial hydroxyl group on carbon 2. http://togogenome.org/gene/10090:Emx2 ^@ http://purl.uniprot.org/uniprot/Q04744 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EMX homeobox family.|||Expressed in immature and mature olfactory sensory neurons (at protein level) (PubMed:15247416). Cerebral cortex (PubMed:1352754).|||Interacts with translation initiation factor EIF4E.|||Nucleus|||Transcription factor, which in cooperation with EMX1, acts to generate the boundary between the roof and archipallium in the developing brain. May function in combination with OTX1/2 to specify cell fates in the developing central nervous system.|||axon http://togogenome.org/gene/10090:Vmn1r168 ^@ http://purl.uniprot.org/uniprot/K7N6B6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem186 ^@ http://purl.uniprot.org/uniprot/Q78HW2|||http://purl.uniprot.org/uniprot/Q9CR76 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the MCIA complex, required for efficient assembly of the mitochondrial complex I.|||Belongs to the TMEM186 family.|||Membrane|||Mitochondrion inner membrane|||Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Interacts with MT-ND3. http://togogenome.org/gene/10090:Cers6 ^@ http://purl.uniprot.org/uniprot/H3BL08|||http://purl.uniprot.org/uniprot/Q8C172 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563).|||Broadly expressed, with highest levels in kidney and brain (at protein level).|||Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) (PubMed:15823095, PubMed:18541923, PubMed:23760501, PubMed:31150623). Can use other acyl donors, but with less efficiency (PubMed:18541923). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively. Ceramides generated by CERS6 play a role in inflammatory response (PubMed:22544924). Acts as a regulator of metabolism and hepatic lipid accumulation (PubMed:25295788, PubMed:30655217, PubMed:31150623). Under high fat diet, palmitoyl- (C16:0-) ceramides generated by CERS6 specifically bind the mitochondrial fission factor MFF, thereby promoting mitochondrial fragmentation and contributing to the development of obesity (PubMed:31150623).|||Endoplasmic reticulum membrane|||Membrane|||Mice show behavioral abnormalities including a clasping abnormality of their hind limbs and a habituation deficit (PubMed:23760501). Knockout mice are protected against high fat diet-induced obesity and glucose intolerance (PubMed:25295788, PubMed:31150623). Mice show decreased palmitoyl (C16:0) ceramide pools and increased energy expenditure (PubMed:25295788, PubMed:31150623). Conditional deletion in brown adipose tissue or liver also protects mice against high fat diet-induced obesity, while it is not the case with specific deletion in myeloid cells (PubMed:25295788).|||N-glycosylated (PubMed:15823095, PubMed:23760501). Glycosylation on Asn-18 is not necessary for function (PubMed:15823095).|||Nucleus|||Phosphorylated at the C-terminus by CK2.|||Some prediction bioinformatics tools predict the presence of a homeobox domain (By similarity). However, the domain is degenerate and residues that are important for DNA-binding are absent (By similarity). Moreover, the protein localizes in the endoplasmic reticulum and not in the nucleus, strongly suggesting that it does not constitute a canonical homeobox domain (PubMed:15823095).|||Up-regulated in liver in response to high-fat diet. http://togogenome.org/gene/10090:Peli1 ^@ http://purl.uniprot.org/uniprot/Q5SRW7|||http://purl.uniprot.org/uniprot/Q8C669 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the pellino family.|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (By similarity). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation (PubMed:16951688). Mediates 'Lys-48'-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation; preferentially recognizes and mediates the degradation of the 'Thr-182' phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates 'Lys-63'-linked ubiquitination of RIPK1 (By similarity).|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.|||Interacts with MAP3K7 (By similarity). Upon IL1B treatment, forms a complex with TRAF6, IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression (PubMed:16951688). Interacts (via atypical FHA domain) with RIPK3 (PubMed:29883609). Binds preferentially to the 'Thr-182' phosphorylated form of RIPK3 (By similarity). Interacts with RIPK1 (PubMed:29883609).|||Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase activity.|||Sumoylated. http://togogenome.org/gene/10090:Klf11 ^@ http://purl.uniprot.org/uniprot/Q8K1S5 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||By TGF-beta. Expressed in a circadian manner in the kidney and epididymal fat tissue.|||Interacts with SIN3A.|||Mice breed normally and are fertile. Hematopoiesis at all stages of development is normal and there is no effect on globin gene expression or longevity.|||Nucleus|||Transcription factor. Activates the epsilon- and gamma-globin gene promoters and, to a much lower degree, the beta-globin gene and represses promoters containing SP1-like binding sites inhibiting cell growth (By similarity). Represses transcription of SMAD7 which enhances TGF-beta signaling. Induces apoptosis. http://togogenome.org/gene/10090:Nt5c3 ^@ http://purl.uniprot.org/uniprot/Q9D020 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pyrimidine 5'-nucleotidase family.|||Cytoplasm|||Isoform 2 is highly expressed in the brain, heart, spleen, kidney and blood. Isoform 2 is expressed (at protein level) in the spleen, skeletal muscle and gastrointestinal epithelia.|||Isoform 2 is weakly expressed from 7.5 dpc and the expression level steadily increases through gestation. At 9.5 dpc and 10.5 dpc is first detected colocalizing with embryonic blood cells within the region of the septum transversum and within the cardiac chambers and dorsal aorta. At 12.5 dpc expression is found in the ventral neural tube and in the trigeminal ganglia and in the liver and dorsal root ganglia. Expression persists in the liver, dorsal root and trigeminal ganglia at 13.5 dpc and weaker expression becomes apparent in cardiac and skeletal muscle. At 16.5 dpc expression is detected in liver, myocardium, tongue, bronchial epithelium, gastrointestinal epithelium, cartilage and forebrain neuroepithelium.|||Monomer.|||Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP). CMP seems to be the preferred substrate. http://togogenome.org/gene/10090:Scube1 ^@ http://purl.uniprot.org/uniprot/Q68EF9|||http://purl.uniprot.org/uniprot/Q6NZL8 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Could be proteolytically cleaved to release a smaller active fragment.|||Could function as an adhesive molecule and its matrix bound and soluble fragments may play a critical role in vascular biology.|||Down-regulated by inflammatory cytokines.|||Expressed predominantly in the developing gonad, nervous system somites, surface ectoderm and limb buds.|||Forms homooligomers and heterooligomers with SCUBE2 and SCUBE3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Epha1 ^@ http://purl.uniprot.org/uniprot/Q60750 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts (kinase activity-dependent) with PTK2/FAK1 (By similarity).|||In myogenic progenitor cells, expressed during the acquisition of muscle stem cell properties, from 18.5 dpc to adulthood.|||Mice display a partially-penetrant uterovaginal and tail development defects. The uterovaginal defect is due to a defect in apoptosis during development.|||Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1 (By similarity).|||Preferentially expressed in epithelial cells including skin, kidney, liver and thymus (PubMed:11519828, PubMed:18802966). Expressed in myogenic progenitor cells (PubMed:27446912).|||Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.|||Ubiquitinated. http://togogenome.org/gene/10090:Pogz ^@ http://purl.uniprot.org/uniprot/Q8BZH4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Cytoplasm|||Interacts with CBX1, CBX3, MAD2L2 and CHAMP1. Interacts with CBX5; POGZ competes with PXVXL motif-containing proteins such as INCENP and TRIM28 for interaction with CBX5 (By similarity). Interacts (via IBM motif) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (By similarity). Interacts with HDGFL2 (By similarity).|||Nucleus|||Phosphorylation increases its interaction with PSIP1.|||Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms (By similarity). Promotes the repair of DNA double-strand breaks through the homologous recombination pathway (By similarity). http://togogenome.org/gene/10090:Med13l ^@ http://purl.uniprot.org/uniprot/A0A0J9YUA8|||http://purl.uniprot.org/uniprot/E9QLJ3|||http://purl.uniprot.org/uniprot/Q6GQS5|||http://purl.uniprot.org/uniprot/Q6JPI3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mediator complex subunit 13 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.|||Highly expressed in heart and weakly expressed in brain, spleen, lung, liver, kidney and testis.|||Nucleus http://togogenome.org/gene/10090:Npb ^@ http://purl.uniprot.org/uniprot/A2ABY0|||http://purl.uniprot.org/uniprot/A2ABY2|||http://purl.uniprot.org/uniprot/Q3UR83|||http://purl.uniprot.org/uniprot/Q8K4P1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neuropeptide B/W family.|||Detected in brain; more specifically in paraventricular hypothalamic nucleus, hippocampus and several nuclei in midbrain and brainstem.|||Has an effect in food intake, on locomotor activity and has an analgesic effect, (in vivo pharmacological studies). May be involved in the regulation of neuroendocrine system, memory and learning (By similarity).|||Secreted http://togogenome.org/gene/10090:Vmn1r50 ^@ http://purl.uniprot.org/uniprot/Q9EP51 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in a subset of sensory neurons located in the apical layer of the vomeronasal organ.|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Arhgef17 ^@ http://purl.uniprot.org/uniprot/Q80U35 ^@ Function ^@ Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. http://togogenome.org/gene/10090:Cox16 ^@ http://purl.uniprot.org/uniprot/E9Q3U7|||http://purl.uniprot.org/uniprot/G3UWC6|||http://purl.uniprot.org/uniprot/Q497I8|||http://purl.uniprot.org/uniprot/Q9CR63 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the MITRAC complex. Interacts with MT-CO2/COX; specifically interacts with newly synthesized MT-CO2/COX. Interacts with SCO1, SCO2 and COA6.|||Belongs to the COX16 family.|||Membrane|||Mitochondrion inner membrane|||Required for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Promotes the insertion of copper into the active site of cytochrome c oxidase subunit II (MT-CO2/COX2). Interacts specifically with newly synthesized MT-CO2/COX and its copper center-forming metallochaperones SCO1, SCO2 and COA6. Probably facilitates MT-CO2/COX2 association with the MITRAC assembly intermediate containing MT-CO1/COX1, thereby participating in merging the MT-CO1/COX1 and MT-CO2/COX2 assembly lines. http://togogenome.org/gene/10090:Or5b3 ^@ http://purl.uniprot.org/uniprot/Q8VFW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpr150 ^@ http://purl.uniprot.org/uniprot/Q8BL07 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Rorc ^@ http://purl.uniprot.org/uniprot/A0A0G2JGZ6|||http://purl.uniprot.org/uniprot/A0A0R4J096|||http://purl.uniprot.org/uniprot/P51450 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches (PubMed:10602018, PubMed:14691482, PubMed:16148126). Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus (PubMed:16990136, PubMed:18164222, PubMed:26607793). May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus (PubMed:9881970, PubMed:10602018, PubMed:14691482, PubMed:16148126, PubMed:16990136, PubMed:18164222). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (By similarity).|||Expressed in immature Vgamma2 gamma-delta T-cells (at protein level) (PubMed:23562159). Expressed in the liver (PubMed:17666523, PubMed:22753030). Expressed in the heart (PubMed:17666523). Expressed in the kidney, jejunum, and brown adipose tissue (PubMed:22753030).|||Expressed in muscle and the thymus (PubMed:9881970, PubMed:10602018). Expressed in the brain, heart, kidney, liver, and lung (PubMed:9881970). Expressed in testes (PubMed:10602018). Not expressed in the spleen or bone marrow (PubMed:9881970).|||Expressed in the thymus, primarily in immature thymocytes, including Vgamma2 gamma-delta T-cells (at protein levels) (PubMed:9881970, PubMed:10602018). Also expressed in a subset of mature T(H)17 cells (PubMed:18164222). Not expressed in the spleen or bone marrow (PubMed:9881970).|||In 3T3-L1 cells, sharp decline at mRNA and protein levels upon induction of adipocyte differentiation. Isoform 2 is detected in the immediate vicinity of vessels among small clusters of CD45(+) cells as early as 12.5 dpc. At 16.5 dpc, isoform 2 is expressed exclusively in tight clusters of cells found in lymph node anlagen, in the submucosal region of the intestine and around central vessels in the spleen.|||Interacts (via AF-2 motif) with the coactivators NCOA1, NCOA2 and PPARGC1A (via LXXLL motif) (PubMed:16148126, PubMed:17476214, PubMed:21499262). Interacts with the corepressor NCOR1 (PubMed:21499262). Interacts with CRY1 (PubMed:22170608). Interacts (via AF-2 motif) with PROX1 (PubMed:23723244). Interacts with FOXP3 (PubMed:18368049). Interacts with NR0B2 (PubMed:25212631).|||Isoform 1 expression oscillates diurnally in peripheral tissues such as liver, brown adipose tissue (BAT), kidney and small intestines. Isoform 2 is induced upon antigen receptor ligation in the presence of IL6 and TGB1 (via STAT3). Induced by TGFB1 in T-cells.|||Mice show decreased adipocytes size and highly insulin sensitivity, leading to an improved control of circulating fatty acids. Mutants are protected from hyperglycemia and insulin resistance in the state of obesity. Loss of circadian pattern of some clock genes expression in the peripheral tissues and massive apoptosis of thymocytes. Knockout mice for isoform 2 lack all lymph nodes and Peyer's patches, as well as LTi cells. They also show a reduction of T(H)17 cells in the lamina propria by at least 10-fold to less than 1% of the T(H) cells. Mice are less susceptible to autoimmune inflammatory diseases.|||Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts (PubMed:17666523, PubMed:19381306, PubMed:19965867, PubMed:21853531, PubMed:22789990, PubMed:23723244). Regulates the circadian expression of clock genes such as CRY1, BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner (PubMed:22753030). Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock (PubMed:22753030). Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1 (PubMed:21853531). Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization.|||Nucleus|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2. http://togogenome.org/gene/10090:Tnfaip8 ^@ http://purl.uniprot.org/uniprot/Q921Z5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a negative mediator of apoptosis. Suppresses the TNF-mediated apoptosis by inhibiting caspase-8 activity but not the processing of procaspase-8, subsequently resulting in inhibition of BID cleavage and caspase-3 activation (By similarity).|||Belongs to the TNFAIP8 family.|||Cytoplasm http://togogenome.org/gene/10090:Triap1 ^@ http://purl.uniprot.org/uniprot/Q9D8Z2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIAP1/MDM35 family.|||Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Likewise, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis.|||Mitochondrion|||Mitochondrion intermembrane space|||Monomer. Interacts with APAF1 and HSP70. Forms a complex with PRELID1 in the mitochondrion intermembrane space. Interacts with PRELID3A. http://togogenome.org/gene/10090:Tmem126b ^@ http://purl.uniprot.org/uniprot/Q9D1R1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the MCIA complex, involved in the assembly of the mitochondrial complex I. Participates in constructing the membrane arm of complex I.|||Belongs to the TMEM126 family.|||Mitochondrion membrane|||Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Associates with the intermediate 370 kDa subcomplex of incompletely assembled complex I. Interacts with TMEM70 (By similarity). http://togogenome.org/gene/10090:Wfdc21 ^@ http://purl.uniprot.org/uniprot/Q8BTE6 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ May promote activation of the metalloproteinase MMP2.|||Predominantly expressed in white adipose tissue and liver.|||Secreted|||Up-regulated by TNF-alpha and lipopolysaccharide (LPS) in vitro. http://togogenome.org/gene/10090:Arhgap26 ^@ http://purl.uniprot.org/uniprot/Q6ZQ82 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds to the C-terminus of PTK2/FAK1 (By similarity). Interacts with NYAP1, NYAP2 and MYO16.|||GTPase-activating protein for RHOA and CDC42.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Coq2 ^@ http://purl.uniprot.org/uniprot/Q66JT7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UbiA prenyltransferase family.|||Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis (PubMed:20526342). Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl donor (such as all-trans-nonaprenyl diphosphate) (PubMed:20526342). The length of the polyprenyl side chain varies depending on the species, in humans, the side chain is comprised of 10 isoprenyls producing CoQ10 (also known as ubiquinone), whereas rodents predominantly generate CoQ9 (PubMed:20526342). However, this specificity is not complete, human tissues have low amounts of CoQ9 and rodent organs contain some CoQ10 (By similarity). Plays a central role in the biosynthesis of CoQ9 (PubMed:20526342). CoQ9 is a vital molecule that transports electrons from mitochondrial respiratory chain complexes (PubMed:20526342). CoQs also function as cofactors for uncoupling protein and play a role as regulators of the extracellularly-induced ceramide-dependent apoptotic pathway (By similarity). Regulates mitochondrial permeability transition pore (mPTP) opening and ROS production (pivotal events in cell death) in a tissue specific manner (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ss18l2 ^@ http://purl.uniprot.org/uniprot/Q9D174 ^@ Similarity ^@ Belongs to the SS18 family. http://togogenome.org/gene/10090:Tbl1xr1 ^@ http://purl.uniprot.org/uniprot/Q8BHJ5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat EBI family.|||Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1XR1, CORO2A and GPS2. Probable component of some E3 ubiquitin ligase complex. Interacts with histones H2B and H4 (By similarity). Interacts with MECP2; bridges interaction between MECP2 and NCOR1 (PubMed:28348241). Interacts with USP44 (By similarity).|||F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation (By similarity).|||Nucleus|||The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes. http://togogenome.org/gene/10090:ND4 ^@ http://purl.uniprot.org/uniprot/P03911|||http://purl.uniprot.org/uniprot/Q7JCY6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 4 family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.|||Membrane|||Mitochondrion inner membrane|||Mitochondrion membrane http://togogenome.org/gene/10090:Cenpw ^@ http://purl.uniprot.org/uniprot/Q3URR0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-W/WIP1 family.|||Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation (By similarity). The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres (By similarity). Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPW has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis (By similarity).|||Heterodimer with CENPT; this dimer coassembles with CENPS-CENPX heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex, which is a subcomplex of the large constitutive centromere-associated network (CCAN, also known as the interphase centromere complex or ICEN). Interacts with NPM1.|||Nucleus|||Nucleus matrix|||centromere|||kinetochore|||nucleolus http://togogenome.org/gene/10090:Zfp638 ^@ http://purl.uniprot.org/uniprot/Q61464 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Due to intron retention.|||In an vitro adipocyte differentiation system, induced at the protein and RNA levels shortly after exposure to the induction mixture. Levels peak before PPARG induction and rapidly decrease during later stages of differentiation.|||Interacts with FHL2 (By similarity). Interacts with CEBPA, CEBPD and CEBPG (PubMed:21602272). Interacts with MPHOSPH8 and TASOR components of the HUSH complex; leading to recruitment of the HUSH complex (By similarity). Interacts with SETDB1 (By similarity). Interacts with HDAC1 (By similarity). Interacts with HDAC4 (By similarity).|||Nucleus speckle|||The matrin-type zinc finger domain is required for localization to nuclear speckles.|||Transcription factor that binds to cytidine clusters in double-stranded DNA (By similarity). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (PubMed:21602272). May also regulate alternative splicing of target genes during adipogenesis (PubMed:25024404). http://togogenome.org/gene/10090:Dnase1l1 ^@ http://purl.uniprot.org/uniprot/A0A158SIT2|||http://purl.uniprot.org/uniprot/Q9D7J6 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DNase I family.|||Endoplasmic reticulum|||Highly expressed in heart and skeletal muscles. Low expression in brain and thymus. Intermediated expression in other tissues. http://togogenome.org/gene/10090:Gm20910 ^@ http://purl.uniprot.org/uniprot/J3QPX2 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Tab3 ^@ http://purl.uniprot.org/uniprot/Q571K4 ^@ Domain|||Function|||PTM|||Subunit ^@ Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains. The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1.|||Degraded in a lysosome-dependent manner following interactiuon with TRIM38.|||Interacts with TAB1, TAB2, MAP3K7, TRAF2 and TRAF6. The minimal TAB3-containing complex (TAB1-MAP3K7-TAB3) appears not to contain TAB2. However, it seems sensible to consider that TAB2 may also join this complex and may act in a cooperative manner with TAB3. Interacts with DYNC2I2 (via the WD domains). Interacts with RBCK1. Binds 'Lys-63'-linked polyubiquitin chains. Interacts with TRIM5. Interacts with TRIM38 (via B30.2/SPRY domain), leading to its translocation to lysosomes and degradation.|||Phosphorylated at Ser-510 by MAPKAPK2 and MAPKAPK3 following IL1 treatment.|||The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins.|||Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitinated by AMFR via 'Lys-27'-linked polyubiquitination; leading to TAK1/MAP3K7 activation. http://togogenome.org/gene/10090:Npr2 ^@ http://purl.uniprot.org/uniprot/Q6VVW5 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds ligand, but no cyclase activation.|||Cell membrane|||Fail to bind the ligand.|||Glycosylated.|||Mice mainly display dwarfism associated with impairment of endochondral ossification, reduced growth of longitudinal vertebra and limb-bone. Self-clasping and priapism that could be due to neuronal disorder are detected. The development of the female reproductive organ is affected.|||Phosphorylated. Phosphorylation of the protein kinase-like domain is required for full activation by CNP.|||Receptor for the C-type natriuretic peptide NPPC/CNP hormone. Has guanylate cyclase activity upon binding of its ligand. May play a role in the regulation of skeletal growth.|||Widely expressed. Expressed in the columnar proliferating and prehypertrophic chondrocyte layers of the tibia. http://togogenome.org/gene/10090:Ifitm5 ^@ http://purl.uniprot.org/uniprot/O88728 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||By interferons.|||Cell membrane|||Detected in embryonic bone (at protein level) (PubMed:18442316). Highly expressed in osteoblasts of adults and embryos. Expressed in primitive hemopoietic cells.|||Embryonic lethality, leading to the birth of only 7% homozygous mutant pups, instead of the expected 25%. Only two out of eight pups were female. Crossing homozygous mice gave rise to about one sixth of the normal litter size, and many newborns died within 48 hours after birth. Homozygous newborns display no striking phenotype other than smaller bones and especially shorter long bones, and this phenotype persists into adulthood. The radius, ulna and tibia are frequently bent in newborns, but this is no longer the case in young adults.|||In embryos at 16.5 dpf, detected in lumbar and thoracic vertebra, the basisphenoid bone, the mandible, the coronal suture between the frontal and parietal bones, the maxilla, the nasal bone and the palate, as well as in the bone collars of long bones and digital bones in hind limbs, and in the primary ossification center.|||Interacts with FKBP11.|||Membrane topology is controversial. The N-terminus is cytoplasmic and the C-terminus extracellular according to PubMed:24715519, while both the N-terminus and the C-terminus are extracellular according to PubMed:18442316.|||Palmitoylated.|||Required for normal bone mineralization. http://togogenome.org/gene/10090:Rapgef2 ^@ http://purl.uniprot.org/uniprot/E9QNQ4|||http://purl.uniprot.org/uniprot/Q6NXI4 ^@ Similarity ^@ Belongs to the RAPGEF2 family. http://togogenome.org/gene/10090:Ugt1a6b ^@ http://purl.uniprot.org/uniprot/K9J7B2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Cited1 ^@ http://purl.uniprot.org/uniprot/P97769|||http://purl.uniprot.org/uniprot/Q3UGA1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CITED family.|||Cytoplasm|||Expressed in calvarial osteoblasts. Expressed in nulliparous mammary epithelial cells; absent in pregnant mice and in lacting mammary glands. Also expressed in mammary tumors (at protein level). Expressed only in melanocytes and testis. Expressed at high levels in the strongly pigmented melanoma cells but at low levels in the weakly pigmented cells.|||Expressed in trophectoderm-derived cells of the placenta.|||Homodimer. Binds to RBM14. Interacts (via N-terminus) with HSPA8; the interaction suppresses the association of CITED1 with p300/CBP and SMAD-mediated transcription transactivation. Interacts (via C-terminus) with TOX3 (via HGM box); the interaction increases estrogen-response element (ERE)-dependent transcription and protection against cell death. Interacts with ESR1; the interaction occurs in a estrogen-dependent manner (By similarity). Interacts (unphosphorylated form preferentially and via C-terminus) with EP300. Interacts (via C-terminus) with CREBBP. Interacts with EGR2.|||Mice die shortly after birth. Mice show an abnormal placental development; the spongiotrophoblast layer is irregular in shape and enlarged while the labyrinthine layer is reduced in size, the blood spaces within the labyrinthine are disrupted. Produces more mineralized bone nodules and deposited twice as much calcium in the matrix.|||Nucleus|||Phosphorylated. Phosphorylation changes in a cell cycle-dependent manner and reduces its transcriptional cofactor activity (By similarity).|||Transcriptional coactivator of the p300/CBP-mediated transcription complex. Enhances SMAD-mediated transcription by strengthening the functional link between the DNA-binding SMAD transcription factors and the p300/CBP transcription coactivator complex. Stimulates estrogen-dependent transactivation activity mediated by estrogen receptors signaling; stabilizes the interaction of estrogen receptor ESR1 and histone acetyltransferase EP300. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Induces transcription from estrogen-responsive promoters and protection against cell death. Potentiates EGR2-mediated transcriptional activation activity from the ERBB2 promoter. Acts as an inhibitor of osteoblastic mineralization through a cAMP-dependent parathyroid hormone receptor signaling. May play a role in pigmentation of melanocytes. Associates with chromatin to the estrogen-responsive TGF-alpha promoter region in a estrogen-dependent manner.|||Up-regulated by parathyroid hormone, forskolin and phorbol ester in osteoblasts. http://togogenome.org/gene/10090:Eps15l1 ^@ http://purl.uniprot.org/uniprot/Q60902 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with EPS15, AGFG1/HRB and AGFG2/HRBL. Associates with the clathrin-associated adapter protein complex 2 (AP-2). Interacts with FCHO1 (By similarity). Interacts with FCHO2. Interacts (via EH domains) with DAB2. Interacts with UBQLN1 (via ubiquitin-like domain). Interacts with CAVIN3 (via leucine-zipper domain) (By similarity). Interacts with REPS2 (By similarity).|||Nucleus|||Phosphorylated on tyrosine residues by EGFR.|||Seems to be a constitutive component of clathrin-coated pits that is required for receptor-mediated endocytosis. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2 (By similarity).|||coated pit http://togogenome.org/gene/10090:Eif2ak4 ^@ http://purl.uniprot.org/uniprot/Q9QZ05 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Kinase activity is enhanced by alphavirus genomic RNA sequences (PubMed:16601681). Kinase activity is stimulated upon binding to uncharged tRNAs (PubMed:16601681). Activated by serum starvation (in vitro) (PubMed:10504407).|||(Microbial infection) Plays a role in modulating the adaptive immune response to Yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation.|||(Microbial infection) Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication.|||Autophosphorylated; autophosphorylation on Thr-898 is increased upon amino acid starvation and in UV irradiation cells and inhibited in presence of IMPACT (PubMed:10504407, PubMed:10655230, PubMed:11106749, PubMed:12176355, PubMed:16601681, PubMed:24333428).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.|||Cytoplasm|||Expressed in liver (PubMed:10504407). Expressed predominantly in the hippocampal CA1 region and the dentate gyrus, and to a lesser degree in CA3 (at protein level) (PubMed:16121183). Expressed in liver, lung, brain, kidney, skeletal muscle and testis (PubMed:10504407, PubMed:10655230). Expressed weakly in heart and spleen (PubMed:10655230). Expressed in the hippocampal CA1 and CA3 regions, the dentate gyrus and cerebellum (PubMed:16121183). Isoform 1 is widely expressed (PubMed:12215525). Isoform 1 is expressed in brain, liver, skeletal muscle and testis (PubMed:10655230). Isoform 3 is expressed in lung, brain, testis, prostate and choroid plexus (PubMed:12215525). Isoform 4 is expressed in muscle, lung, kidney, brain, testis and prostate (PubMed:10655230, PubMed:12215525).|||Homodimer; homodimerization is important for kinase activation by uncharged tRNAs (By similarity). Interacts with GCN1; this interaction stimulates EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety of stress conditions, such as amino acid depletion, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation (PubMed:24333428). Interacts with DNAJC3; this interaction inhibits EIF2AK4/GCN2 kinase activity during endoplasmic reticulum (ER), hypothermic and amino acid-starving stress conditions (PubMed:25329545). Interacts with MAP3K20; activates EIF2AK4/GCN2 kinase activity in response to moderate ribotoxic stress (By similarity).|||Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:10504407, PubMed:10655230, PubMed:12176355, PubMed:12215525, PubMed:15213227, PubMed:16054071, PubMed:16176978, PubMed:16121183, PubMed:15774759, PubMed:16601681, PubMed:26102367). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (PubMed:10655230, PubMed:11106749, PubMed:12176355, PubMed:15213227, PubMed:16176978, PubMed:26102367). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:10655230, PubMed:11106749, PubMed:12176355, PubMed:15213227, PubMed:16176978, PubMed:26102367). Required for the translational induction of protein kinase PRKCH following amino acid starvation (PubMed:19797084). Binds uncharged tRNAs (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:16176978, PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (PubMed:16121183). Plays a role in neurite outgrowth inhibition (PubMed:23447528). Plays a role in feeding behavior to maintain amino acid homeostasis; contributes to the innate aversion toward diets of imbalanced amino acid composition (PubMed:16054071, PubMed:15774759). Plays a proapoptotic role in response to glucose deprivation (PubMed:20660158). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (PubMed:12176355).|||Mice are viable, fertile, and exhibit no phenotypic abnormalities under standard growth conditions (PubMed:12215525). Show an increase in prenatal and neonatal mortalities when essential amino acids are absent in the maternal diet during gestation (PubMed:12215525, PubMed:15213227). In response to nutrient deprivation, display reduced abilities to chronically down-regulate hepatic protein synthesis, resulting in preservation of liver mass relative to body size and enhanced skeletal muscle loss (PubMed:15213227). Mice exhibit a lowered threshold for the induction of strong and robust long-term potentiation (LTP) in the CA1 neurons of the hippocampus and the consolidation of long-term memory (PubMed:16121183). Knockout and conditional knockout in the brain result in a diminution of the rate of food consumption and an impairment in the food aversion response in mice fed an imbalanced amino acid diet (PubMed:16054071). Mice are more susceptible to intranasal Sindbis virus infection, with high virus titers in the brain compared to similarly infected control animals (PubMed:16601681). Mice infected with yellow fever virus show a decrease in dendritic cell autophagy and an impairment in their capacity to present antigens to T-cells under amino acid starvation (PubMed:24310610).|||The histidyl-tRNA synthetase-like region and protein kinase domains are necessary for eIF-2-alpha kinase activity and eIF-2-alpha-mediated translational control (PubMed:10655230). The histidyl-tRNA synthetase-like domain is necessary for binding to uncharged tRNAs (PubMed:16601681). Kinase domain 1 is a degenerate kinase domain (PubMed:10504407). http://togogenome.org/gene/10090:Icam2 ^@ http://purl.uniprot.org/uniprot/P35330 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. ICAM family.|||Expressed in endothelial cells and leukocytes. High levels found in lung.|||ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM2 may play a role in lymphocyte recirculation by blocking LFA-1-dependent cell adhesion. It mediates adhesive interactions important for antigen-specific immune response, NK-cell mediated clearance, lymphocyte recirculation, and other cellular interactions important for immune response and surveillance.|||Interacts with RDX, EZR and MSN.|||Membrane|||microvillus http://togogenome.org/gene/10090:Or52e8 ^@ http://purl.uniprot.org/uniprot/Q7TRP2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5m9 ^@ http://purl.uniprot.org/uniprot/A0A1L1ST14 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nsdhl ^@ http://purl.uniprot.org/uniprot/Q3US15|||http://purl.uniprot.org/uniprot/Q9R1J0 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 3-beta-HSD family.|||Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis (PubMed:10369263, PubMed:14567972). Plays a role in the regulation of the endocytic trafficking of EGFR (PubMed:23125191).|||Defects in Nsdhl are the cause of male-lethal mutations bare patches (Bpa) and striated (Str) phenotypes. Heterozygous Bpa females are dwarfed and demonstrate abnormal deposits of calcium in tail vertebrae. They also develop a hyperkeratotic skin eruption shortly after birth that resolves, leaving 'bare patches' arranged in a horizontal, striped pattern. The Str females are indistinguishable from normal littermates until postnatal day 12-14 when they develop striations in their coat.|||Endoplasmic reticulum membrane|||Homodimer.|||Lipid droplet http://togogenome.org/gene/10090:Apof ^@ http://purl.uniprot.org/uniprot/Q91V80 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the apolipoprotein F family.|||Liver.|||Minor apolipoprotein that associates with LDL. Inhibits cholesteryl ester transfer protein (CETP) activity and appears to be an important regulator of cholesterol transport. Also associates to a lesser degree with VLDL, Apo-AI and Apo-AII.|||Secreted http://togogenome.org/gene/10090:Tmem208 ^@ http://purl.uniprot.org/uniprot/Q9CR96|||http://purl.uniprot.org/uniprot/S4R1H6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM208 family.|||Endoplasmic reticulum membrane|||May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.|||Membrane http://togogenome.org/gene/10090:Galnt15 ^@ http://purl.uniprot.org/uniprot/Q9D2N8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Although it displays a much weaker activity toward all substrates tested compared to GALNT2, it is able to transfer up to seven GalNAc residues to the Muc5AC peptide, suggesting that it can fill vicinal Thr/Ser residues in cooperation with other GALNT proteins. Prefers Muc1a as substrate (By similarity).|||Golgi apparatus membrane|||Specifically expressed in testis.|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Aire ^@ http://purl.uniprot.org/uniprot/B2MVU6|||http://purl.uniprot.org/uniprot/Q3ZB65|||http://purl.uniprot.org/uniprot/Q3ZB71|||http://purl.uniprot.org/uniprot/Q9Z0E3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Deficient mice show an altered thymic organization with altered morphology and location of mTECs (PubMed:19015306). They exhibit defective accumulation of thymic dendritic cells in the medullary region and generation of naturally ocurring T cells in the thymus (PubMed:21300913).|||Highly expressed in a few cells in the medulla of the thymus (medullary epithelial cells) (at protein level) (PubMed:23993652). Expressed in thymic but no peripheral B-cells (PubMed:26070482). In secondary lymphoid organs, expressed in a discrete population of bone marrow-derived toleregenic antigen presenting cells (APCs) called extrathymic AIRE expressing cells (eTAC)(at protein level) (PubMed:23993652). Detected at very low levels in thymus, lymph node, liver, brain, ovary, lung, testis, kidney, heart, spleen, bone marrow, skeletal muscle and adrenal gland. Isoforms 1a to 1d predominate, isoforms 2a to 2d are intermediate and isoforms 3a to 3d are expressed at extremely low levels.|||Homodimer and homotetramer. Interacts with CREBBP. Interacts preferentially with histone H3 that is not methylated at 'Lys-4'. Binds with lower affinity to histone H3 that is monomethylated at 'Lys-4'. Trimethylation of histone H3 at 'Lys-4' or phosphorylation at 'Thr-3' abolish the interaction. Binds with lower affinity to histone H3 that is acetylated at 'Lys-4', or that is acetylated at 'Lys-9' or trimethylated at 'Lys-9'. Binds histone H3 that is dimethylated at 'Arg-2' with very low affinity (By similarity).|||In the thymus, not expressed at 13.5 dpc but present at 16.5 dpc and postnatal day 1.|||Interacts via the first PHD domain with the N-terminus of histone H3 that is not methylated at 'Lys-4'. Disruption of the first PHD domain has been shown to lead to reduced transcriptional activity and to localization of the protein mainly in the cytoplasm in small granules. While the PHD zinc fingers are necessary for the transactivation capacity of the protein, other regions also modulate this function (By similarity).|||Nucleus|||Phosphorylated.|||Probably inactive.|||The L-X-X-L-L repeats may be implicated in binding to nuclear receptors.|||The N-terminal HSR domain is required for localization on tubular structures.|||Transcription factor playing an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the periphery, called tissue restricted antigens (TRA) (Probable). Binds to G-doublets in an A/T-rich environment; the preferred motif is a tandem repeat of 5'-. ATTGGTTA-3' combined with a 5'-TTATTA-3' box. Binds to nucleosomes (By similarity). Binds to chromatin and interacts selectively with histone H3 that is not methylated at 'Lys-4', not phosphorylated at 'Thr-3' and not methylated at 'Arg-2'. Functions as a sensor of histone H3 modifications that are important for the epigenetic regulation of gene expression. Mainly expressed by medullary thymic epithelial cells (mTECs), induces the expression of thousands of tissue-restricted proteins, which are presented on major histocompatibility complex class I (MHC-I) and MHC-II molecules to developing T-cells percolating through the thymic medulla (By similarity). Also induces self-tolerance through other mechanisms such as the regulation of the mTEC differentiation program (PubMed:19015306). Controls the medullary accumulation of thymic dendritic cells and the development of regulatory T-cell through the regulation of XCL1 expression (PubMed:21300913). Regulates the production of CCR4 and CCR7 ligands in medullary thymic epithelial cells and alters the coordinated maturation and migration of thymocytes (PubMed:19923453). In thimic B-cells, allows the presentation of licensing-dependent endogenous self-anitgen for negative selection (PubMed:26070482). In secondary lymphoid organs, induces functional inactivation of CD4(+) T-cells. Expressed by a distinct bone marrow-derived population, induces self-tolerance through a mechanism that does not require regulatory T-cells and is resitant to innate inflammatory stimuli (PubMed:23993652). http://togogenome.org/gene/10090:Vmn1r25 ^@ http://purl.uniprot.org/uniprot/H3BLP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trim59 ^@ http://purl.uniprot.org/uniprot/Q922Y2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||E3 ubiquitin ligase involved in different processes such as development and immune response (PubMed:22588174, PubMed:29467473). Serves as a negative regulator for innate immune signaling pathways by suppressing RLR-induced activation of IRF3/7 and NF-kappa-B via interaction with adapter ECSIT (PubMed:22588174). Regulates autophagy through modulating both the transcription and the ubiquitination of BECN1. On the one hand, regulates the transcription of BECN1 through negatively modulating the NF-kappa-B pathway. On the other hand, regulates TRAF6-mediated 'Lys-63'-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. In addition, mediates 'Lys-48'-linked ubiquitination of TRAF6 and thereby promotes TRAF6 proteasomal degradation. Acts also as a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly and WASH1 'Lys-63'-linked ubiquitination (PubMed:29467473).|||Endoplasmic reticulum membrane|||Interacts with ECSIT (PubMed:22588174).|||Moderately expressed in the spleen, brain and heart and very highly expressed in the testis (PubMed:12095697).|||TRIM59-deficiency causes early embryonic lethality. Affects the expression of gastrulation-associated genes during early embryonic development. http://togogenome.org/gene/10090:Pde2a ^@ http://purl.uniprot.org/uniprot/A0A1B0GRJ9|||http://purl.uniprot.org/uniprot/Q3TYK5|||http://purl.uniprot.org/uniprot/Q5PR72|||http://purl.uniprot.org/uniprot/Q922S4 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abnormally elongated mitochondria. This phenotype is reversed by treatment with the PKA inhibitor H89. Protected from ionomycin- but not staurosporin-induced cell death.|||Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE2 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.|||Cell membrane|||Contains a transit peptide at positions 1-17.|||Cytoplasm|||Expressed in brain and liver (at protein level).|||Homodimer.|||Mitochondrion inner membrane|||Mitochondrion matrix|||Mitochondrion outer membrane|||Regulates mitochondrial cAMP levels and respiration (PubMed:21724846). Involved in the regulation of mitochondria morphology/dynamics and apoptotic cell death via local modulation of cAMP/PKA signaling in the mitochondrion, including the monitoring of local cAMP levels at the outer mitochondrial membrane and of PKA-dependent phosphorylation of DNM1L (PubMed:28463107).|||The 3',5'-cyclic-AMP phosphodiesterase activity is stimulated by 3',5'-cyclic GMP (By similarity). Specifically inhibited by Bay 60-7550 (PubMed:28463107).|||The GAF 1 domain functions as a dimerization domain.|||The GAF 2 domains binds cGMP, which acts as an allosteric activator.|||cGMP-activated cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:21724846). Has a higher efficiency with cGMP compared to cAMP (By similarity). Plays a role in cell growth and migration (By similarity). http://togogenome.org/gene/10090:Lrrc4 ^@ http://purl.uniprot.org/uniprot/Q99PH1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts (via LRR repeats) with NTNG2. Interacts with DLG4. Forms a complex with DLG4 and with NMDA receptors.|||Membrane|||Mutant mice dysplay impaired startle response to acoustic stimulus.|||N-glycosylated.|||Postsynaptic cell membrane|||Specifically expressed in brain. In the hippocampus, parietal cortex and piriform cortex expressed in proximal segments of CA1 pyramidal neurons.|||Synaptic adhesion protein. Regulates the formation of exitatory synapses through the recruitment of pre-and-postsynaptic proteins. Organize the lamina/pathway-specific differentiation of dendrites. Plays an important role for auditory synaptic responses. Involved in the suppression of glioma.|||The last 4 C-terminal residues bind to the first 2 PDZ domains of DLG4. http://togogenome.org/gene/10090:Nlrp5 ^@ http://purl.uniprot.org/uniprot/Q9R1M5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Reduced by T.gondii in the testes and uterus.|||As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:11062459, PubMed:18804437, PubMed:25208553). Required for the formation of F-actin cytoplasmic lattices (CPL) in oocytes, which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning (PubMed:25208553). Required for the localization of cortical granules to the cortex of oocytes, via association with the cortical actin scaffold (PubMed:31118423). Required for cortical actin clearance prior to oocyte exocytosis and prevention of polyspermy (PubMed:31118423). Involved in regulating post-fertilization Ca(2+) release and endoplasmic reticulum storage (ER) storage via regulation of cellular localization (PubMed:24374158). May be involved in the localization of mitochondria to the cytoplasm and perinuclear region in oocytes and early stage embryos, independent of its role in CPL formation (PubMed:22357545).|||Belongs to the NLRP family.|||Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and TLE6 (PubMed:18804437, PubMed:28992324, PubMed:31575650). Within the complex, interacts with OOEP, KHDC3 and TLE6 (PubMed:18804437, PubMed:28992324, PubMed:31575650). The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments (By similarity). As part of the SCMC interacts with the SCMC-associated protein ZBED3 (PubMed:28992324). As part of the SCMC interacts with the SCMC-associated protein CFL1/Cofilin-1 (PubMed:25208553). Interacts with PRKCE (By similarity). Interacts with TUBB3 at cytoskeleton microtubules (PubMed:24374158).|||Cortical granule|||Cytoplasm|||Expression is first detected in oocytes of type 3A primary follicles (PubMed:14670992, PubMed:31118423). Transcripts accumulate during oogenesis (PubMed:14670992). Expressed in the cytoplasm of germinal vesicle oocytes before becoming concentrated in the subcortex of metaphase 2 oocytes (PubMed:28992324, PubMed:31118423). During meiotic maturation, the vast majority of the transcripts are degraded and virtually none is detected by 2-cell stage embryogenesis (PubMed:14670992, PubMed:18804437). The protein however persists during preimplantation up to the blastocyst stage (PubMed:14670992, PubMed:18804437). At 2-cell stage, excluded from cell-cell contact regions (PubMed:18804437). Continuous exclusion from these regions during preimplantation development leads to the absence of the protein from the inner cells of the morula and the inner cell mass of the blastocyst (PubMed:18804437). Expressed in ovaries at birth, expression peaks at postnatal day 10 (P10), expression is then decreased at P17 and further decreased at P21 (PubMed:10433232, PubMed:31575650).|||Golgi apparatus|||Mice appear phenotypically normal with no apparent defects in ovarian development, oocyte maturation or ovulation (PubMed:14670992, PubMed:22357545). Cortical granules are scattered throughout the cytoplasm in oocytes and ovulated eggs (PubMed:31118423). Reduced abundance of intact MYH9/MyoIIA and MYO5A, the dense cortical actin scaffold remained present prior to exocytosis (PubMed:31118423). Increase in polyspermy in the perivitelline space resulting from a decrease in efficacy of the zona pellucida block. Increase in multiple pronuclei and delay in cortical granule exocytosis and ZP2 cleavage (PubMed:31118423). Embryos form unequal sized blastomeres due to smaller, dysmorphic, and displaced mitotic spindles resulting in asymmetric division (PubMed:25208553). Increase in apoptotic cells in blastomeres which progress beyond the 8-cell stage (PubMed:22357545). Decrease in thickness of subcortical F-actin in zygotes, thickening of F-actin bundles in the cytoplasm and loss of F-actin cytoplasmic lattices (PubMed:25208553). Increase in subcortical mitochondrial clustering of mitochondria in 2-cell embryos (PubMed:22357545). Increase in mitochondria activity, shown by an increase in membrane potential and reactive oxygen species (PubMed:22357545). Decrease in expression of the SCMC-associated protein ZBED3 in the cytoplasm of oocytes (PubMed:28992324). In knockdown mice M2 oocytes show a diffuse ER distribution pattern with a reduced number of cortical ER clusters and random movement of lipid droplets during oocyte maturation (PubMed:24374158). Reduces tubulin localization to the cellular microtubular architecture (PubMed:24374158). Decrease in storage and release of Ca(2+) from the endoplasmic reticulum, and disruption of Ca(2+) oscillations following oocyte fertilization (PubMed:24374158). diffused localization of ITPR1/IP3R-1 throughout the cytoplasm with reduced clustering at the oocyte cortex (PubMed:24374158).|||Mitochondrion|||Phosphorylated by PRKCE.|||nucleolus http://togogenome.org/gene/10090:Tshz2 ^@ http://purl.uniprot.org/uniprot/Q68FE9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the teashirt C2H2-type zinc-finger protein family.|||Expressed in mesenchymal cells in proximal ureters at 14 dpc, preceding the smooth muscle precursor cells differentiation and the expression of contractile proteins from 15 dpc.|||Interacts (via homeobox domain) with APBB1 (via PID domain 1).|||Nucleus|||Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential).|||Sumoylated. http://togogenome.org/gene/10090:Stk38 ^@ http://purl.uniprot.org/uniprot/Q91VJ4 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-281. Thr-444 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-444 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2/HCCA2 to the N-terminal of STK38.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm|||Expressed at high levels in spleen, lung, thymus, brain and fat tissue.|||Homodimeric S100B binds two molecules of STK38. Interacts with MOB1 and MOB2 (By similarity). Interacts with MAP3K1 and MAP3K2 (via the kinase catalytic domain) (By similarity). Forms a tripartite complex with MOBKL1B and STK3/MST2 (By similarity). Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4 (PubMed:21730291).|||ISGylated.|||Negative regulator of MAP3K1/2 signaling. Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (By similarity).|||Nucleus|||Phosphorylated by STK3/MST2 and this is enhanced by MOBKL1B. http://togogenome.org/gene/10090:Eml6 ^@ http://purl.uniprot.org/uniprot/Q5SQM0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat EMAP family.|||May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.|||cytoskeleton http://togogenome.org/gene/10090:Setdb1 ^@ http://purl.uniprot.org/uniprot/D3YYC3|||http://purl.uniprot.org/uniprot/G5E8N3 ^@ Subcellular Location Annotation ^@ Chromosome|||Nucleus http://togogenome.org/gene/10090:Styk1 ^@ http://purl.uniprot.org/uniprot/Q6J9G1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Highly expressed in colon and small intestine. Weakly or not expressed in spleen, skeletal muscle, liver, kidney, heart and brain. Expressed in transformed kidney cell lines (COS-1 and HEK293T).|||Membrane|||Probable tyrosine protein-kinase, which has strong transforming capabilities on a variety of cell lines including NIH 3T3 fibroblasts and on athymic nude mice. When overexpressed, it can also induce tumor cell invasion as well as metastasis in distant organs. May act by activating both MAP kinase and phosphatidylinositol 3'-kinases (PI3K) pathways. http://togogenome.org/gene/10090:Cfdp1 ^@ http://purl.uniprot.org/uniprot/O88271 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected at 8 dpc in developing organs, including brain, heart, lung and intestines. Expressed at 14 dpc and 16 dpc at the periphery of developing organs such as bones and teeth.|||Expressed in lung, liver and heart, with higher expression in teeth.|||May play a role during embryogenesis. May modulate tooth organogenesis since alterations of this protein function affect tooth organs size as well as individual cell fate and survival. In embryonic cells, blockage of the function results in increased number of apoptotic cells, reduced proliferation, alterations in cell shape and fibronection matrix synthesis.|||kinetochore http://togogenome.org/gene/10090:Vmn2r93 ^@ http://purl.uniprot.org/uniprot/L7N1Z9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Lpcat1 ^@ http://purl.uniprot.org/uniprot/Q3TFD2 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Cell membrane|||Constitutively expressed. Not induced by inflammatory stimulation.|||Endoplasmic reticulum membrane|||Exhibits both acyltransferase and acetyltransferase activities (PubMed:16704971, PubMed:18285344, PubMed:18156367). Activity is calcium-independent (PubMed:16704971, PubMed:18285344). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:16704971, PubMed:18285344, PubMed:18156367). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Displays a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively (PubMed:16704971, PubMed:18285344). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (PubMed:18285344). May synthesize phosphatidylcholine in pulmonary surfactant, thereby playing a pivotal role in respiratory physiology (PubMed:16704971). Involved in the regulation of lipid droplet number and size (By similarity).|||Expression increases steadily throughout embryogenesis and decreases slightly in the adult.|||Golgi apparatus membrane|||Lipid droplet|||Not activated by inflammatory stimulation (PubMed:18285344). Inhibited by Cu(2+), Fe(2+), Ca(2+) and Mg(2+) (PubMed:18285344, PubMed:18156367). Activity is not affected by Co(2+) or Mn(2+) (PubMed:18285344).|||Predominantly expressed in lung where it is enriched in alveolar type II cells. Expressed at lower levels in spleen and brain. Also detected in erythroleukemic cells and reticulocytes. Weakly or not expressed in other tissues.|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphocholine.|||The di-lysine motif may confer endoplasmic reticulum localization. http://togogenome.org/gene/10090:Cd2ap ^@ http://purl.uniprot.org/uniprot/Q9JLQ0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Death at 6 to 7 weeks of age from renal failure. Mice show defects in epithelial foot processes, accompanied by mesangial cell hyperplasia and extracellular matrix deposition.|||Expressed in podocytes (at protein level).|||Homodimer. Interacts with F-actin, PKD2, NPHS1 and NPHS2. Interacts with WTIP. Interacts with DDN; interaction is direct. Interacts (via SH3 2 domain) with CBL (via phosphorylated C-terminus). Interacts with BCAR1/p130Cas (via SH3 domain). Interacts with MVB12A and ARHGAP17. Interacts with ANLN, CD2 and CBLB. Interacts with PDCD6IP and TSG101. Interacts with RIN3. Interacts directly with RET (inactive) and CBLC; upon RET activation by GDNF suggested to dissociate from RET as CBLC:CD2AP complex. Interacts with CGNL1 and SH3BP1; probably part of a complex at cell junctions. Interacts with CAPZA1.|||Phosphorylated on tyrosine residues; probably by c-Abl, Fyn and c-Src.|||Potential homodimerization is mediated by the coiled coil domain.|||Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (By similarity). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (PubMed:9741631). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus (PubMed:10514378). Also required for cytokinesis. Plays a role in epithelial cell junctions formation (By similarity).|||cytoskeleton|||ruffle http://togogenome.org/gene/10090:Ak8 ^@ http://purl.uniprot.org/uniprot/Q32M07 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylate kinase family.|||Interacts with CFAP45 and CFAP52; CFAP45 and AK8 dimerization may create a cavity at the interface of the dimer that can accommodate AMP.|||Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. Also displays broad nucleoside diphosphate kinase activity.|||cilium axoneme|||cytosol http://togogenome.org/gene/10090:Chmp1b2 ^@ http://purl.uniprot.org/uniprot/Q9CQD4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||Endosome|||Late endosome membrane|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B and SPAST to the midbody of dividing cells (By similarity).|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with CHMP1A. Interacts with VTA1; the interaction probably involves the open conformation of CHMP1B. Interacts with CHMP2A. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with SPAST (via MIT domain); the interaction is direct. Interacts with IST1. Interacts with MITD1. Interacts with STAMBP (By similarity).|||cytosol http://togogenome.org/gene/10090:Idi1 ^@ http://purl.uniprot.org/uniprot/G3XA48|||http://purl.uniprot.org/uniprot/P58044 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IPP isomerase type 1 family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to its highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).|||Monomer.|||Peroxisome http://togogenome.org/gene/10090:Gm21470 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Med9 ^@ http://purl.uniprot.org/uniprot/Q8VCS6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 9 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Insr ^@ http://purl.uniprot.org/uniprot/M4TKR7|||http://purl.uniprot.org/uniprot/P15208 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated in response to insulin. Autophosphorylation activates the kinase activity. PTPN1, PTPRE and PTPRF dephosphorylate important tyrosine residues, thereby reducing INSR activity. Inhibited by ENPP1. GRB10 and GRB14 inhibit the catalytic activity of the INSR, they block access of substrates to the activated receptor. SOCS1 and SOCS3 act as negative regulators of INSR activity, they bind to the activated INRS and interfere with the phosphorylation of INSR substrates (By similarity). Interacts with PTPRF (By similarity). Interacts with ATIC; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling netwok regulating INSR autophosphorylation and endocytosis (By similarity).|||Autophosphorylated on tyrosine residues in response to insulin (By similarity). Phosphorylation of Tyr-989 is required for IRS1-, SHC1-, and STAT5B-binding (By similarity). Dephosphorylated by PTPRE on Tyr-989, Tyr-1175, Tyr-1179 and Tyr-1180 residues (By similarity). Dephosphorylated by PTPRF and PTPN1 (By similarity). Dephosphorylated by PTPN2 and Ptprv; down-regulates insulin-induced signaling (PubMed:12612081, PubMed:20655470).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Late endosome|||Lysosome|||Membrane|||Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). When present in a hybrid receptor with IGF1R, binds IGF1 (By similarity). In adipocytes, inhibits lipolysis (PubMed:27322061).|||Recycling endosome membrane|||Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains carry the insulin-binding regions, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2 (By similarity). Activated form of INSR interacts (via Tyr-989) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7 (By similarity). Interacts (via the phosphorylated Tyr-989), with SOCS3. Interacts (via the phosphorylated Tyr-1175, Tyr-1179, Tyr-1180) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 (By similarity). Interacts with ARRB2. Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling (By similarity). Interacts with GRB7 (By similarity). Interacts with PDPK1 (By similarity). Interacts (via Tyr-1180) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-989, this results in decreased interaction with, and phosphorylation of, IRS1 (By similarity). Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation (By similarity). Interacts with PTPRE; this interaction is dependent of Tyr-1175, Tyr-1179 and Tyr-1180 of the INSR (By similarity). Interacts with STAT5B (via SH2 domain) (By similarity). Interacts with PTPRF (By similarity). Interacts with the insulin receptor SORL1; this interaction strongly increases its surface exposure, hence strengthens insulin signal reception (PubMed:27322061). Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the INSR C-terminal region (By similarity). Interacts with GNAI3; the interaction is probably mediated by CCDC88A/GIV (By similarity). Interacts with LMBRD1 (PubMed:24078630).|||The tetrameric insulin receptor binds insulin via non-identical regions from two alpha chains, primarily via the C-terminal region of the first INSR alpha chain. Residues from the leucine-rich N-terminus of the other INSR alpha chain also contribute to this insulin binding site. A secondary insulin-binding site is formed by residues at the junction of fibronectin type-III domain 1 and 2 (By similarity). http://togogenome.org/gene/10090:Car2 ^@ http://purl.uniprot.org/uniprot/P00920 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-carbonic anhydrase family.|||Catalyzes the reversible hydration of carbon dioxide (By similarity). Can also hydrate cyanamide to urea (By similarity). Involved in the regulation of fluid secretion into the anterior chamber of the eye (By similarity). Essential for bone resorption and osteoclast differentiation (By similarity). Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption (By similarity). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (By similarity).|||Cell membrane|||Cytoplasm|||Inhibited by acetazolamide.|||Interacts with SLC4A4 (By similarity). Interaction with SLC4A7 regulates SLC4A7 transporter activity (By similarity). Interacts with SLC26A6 (By similarity). http://togogenome.org/gene/10090:Tmem178b ^@ http://purl.uniprot.org/uniprot/Q8BNC6 ^@ Similarity ^@ Belongs to the TMEM178 family. http://togogenome.org/gene/10090:Hsh2d ^@ http://purl.uniprot.org/uniprot/Q6VYH9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein involved in tyrosine kinase and CD28 signaling (By similarity). May be a modulator of the apoptotic response through its ability to affect mitochondrial stability.|||Cytoplasm|||Interacts with FES and TNK2.|||May be phosphorylated by FES and ACK1.|||Mitochondrion|||Predominantly expressed in spleen and thymus. Appears not to be expressed in heart, brain, liver, kidney, embryo, lung and ovary. http://togogenome.org/gene/10090:Ptpro ^@ http://purl.uniprot.org/uniprot/E9Q612 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.|||Interacts (phosphorylated form) with FYN and GRB2.|||Membrane|||Modification of podocyte structure such that the normal octopoid podocyte is simplified to a more amoeboid structure and that the foot processes are shorter and broader than normal. These changes are associated with altered distribution of the podocyte intermediate cytoskeletal protein vimentin/VIM. Mutant animals have a reduced glomerular filtration rate and reduced glomerular nephrin (NPHS1) content. However, there is no evidence of proteinuria. After removal of one or more kidneys, Ptpro-null animals have higher blood pressure than does their wild-type littermates.|||Possesses tyrosine phosphatase activity. Plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function. http://togogenome.org/gene/10090:Or4p20 ^@ http://purl.uniprot.org/uniprot/Q7TR18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ddr2 ^@ http://purl.uniprot.org/uniprot/Q62371 ^@ Activity Regulation|||Caution|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:18483174 Ddr2 is required for male and female fertility, since smallie mice with a 150 kb deletion that extends into the Ddr2 gene are sterile. Smallie males have defects in spermatogenesis (PubMed:19681157). On the other hand, the fertility status of mice with a targeted disruption of the Ddr2 gene has not been mentioned (PubMed:11375938). Thus, the infertility of smallie mice may be due to some additional, not yet identified defect.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Binds hydroxyproline-rich sequence motifs in fibrillar, glycosylated collagen, such as the GQOGVMGFO motif, where O stands for hydroxyproline. Interacts with SRC. Interacts (tyrosine phosphorylated) with SHC1.|||Cell membrane|||Defects in Ddr2 are the cause of the smallie (sli) phenotype. Smallie mice show distinct dwarfing, with reduced body mass and reduced bone mineral content. Mice also have mild craniofacial deformities, such as protuberant eyes and snub noses. Smallie mice have a reduced life span, with about half of them dying within 6 months. Matings between male and female smallie mice do not yield any offspring. The levels of circulating steroid hormones remain at a level corresponding to prepubertal wild-type mice. Adult testes exhibit much reduced numbers of spermatids with atrophy of spermatogonia, Sertoli and Leydig cells. Ovaries show an absence of corpora lutea.|||Mice are born at the expected Mendelian rate, but fail to thrive, resulting in much reduced adult body weight and dwarfing. They exhibit shortening of long bones, irregular growth of flat bones and a shortened snout. Young mice show shortened growth plates in long bones and impaired chondrocyte proliferation. Likewise, cultured fibroblasts from mutant mice show reduced proliferation.|||N-glycosylated.|||Present in an inactive state in the absence of collagen binding and phosphorylation by SRC. Tyrosine phosphorylation enhances the affinity for ATP and the catalytic activity.|||Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing.|||Tyrosine phosphorylated in response to collagen binding. Phosphorylated by SRC; this is required for activation and subsequent autophosphorylation on additional tyrosine residues (By similarity).|||Up-regulated during osteoblast differentiation (in vitro). Up-regulated in cartilage from mice with osteoarthritis.|||Widely expressed. Detected in lung, ovary, skin and in testis Leydig cells (at protein level). Widely expressed. Detected at high levels in heart, lung, skeletal muscle, central nervous system (CNS) and kidney, and at lower levels in brain and testis. Detected in chondrocytes in tibia growth plates of young mice. http://togogenome.org/gene/10090:Or10ak13 ^@ http://purl.uniprot.org/uniprot/A2ACY8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pou4f2 ^@ http://purl.uniprot.org/uniprot/Q63934 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family. Class-4 subfamily.|||Cytoplasm|||Expressed in retinal ganglion cells (RGCs) (PubMed:21875655, PubMed:23805044). Expressed in mature osteoclasts (PubMed:17668438). Expressed in cells of layers of the superior colliculus and the adjacent periaqueductal gray (at protein level) (PubMed:7691107). Expressed in the brain, peripheral sensory nervous system and retina (PubMed:7904822). Expressed in the optical, intermediate, and deep gray areas of the superior colliculus, the dorsal column of the mesencephalic and pontine central gray, and the lateral interpeduncular nucleus of the brain (PubMed:7904822). Expressed predominantly in postmitotic, terminally differentiated neurons (PubMed:7904822). Expressed in ganglion cell layer (GCL) of the retina (PubMed:7691107, PubMed:23805044).|||Isoform 2: Interacts with POU4F1 isoform 1; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities (PubMed:8537352). Isoform 2: Interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (PubMed:9448000). Isoform 2: Interacts (via C-terminus) with TP53 (via N-terminus) (PubMed:17145718). Interacts with DLX1 (via homeobox DNA-binding domain); this interaction suppresses DLX1-mediated transcriptional activity in postnatal retina enhancing retinal ganglion cell (RGC) differentiation (PubMed:21875655). Interacts with DLX2 (via homeobox DNA-binding domain); this interaction enhances RGC differentiation (PubMed:21875655). Isoform 1: Interacts (via C-terminus) with ISL1 (via C-terminus) (PubMed:24643061). Isoform 1: Interacts with ISL2 (PubMed:24643061). Isoform 1: Interacts with LHX2 (PubMed:24643061).|||Mice develop to adulthood and are fertile (PubMed:8637595). Show a reduction in the number of retinal ganglion cells (RGC) and a thinner optic nerve compared to wild-type mice (PubMed:8637595, PubMed:8632990, PubMed:10357904). Show RGC axon pathfinding alterations along the central visual pathways (PubMed:10357904, PubMed:11163266). Show an alteration in the expression levels for several genes involved in the differentiation of RGCs (PubMed:24643061, PubMed:25775587). Display an increase in DLX1 and DLX2 mRNA expression in the embryonic retina, especially in the ganglion cell layer (PubMed:21875655).|||Nucleus|||Nucleus speckle|||The N-terminal transcriptional activation region is sufficient to induce transcriptional activity.|||The POU-specific domain and POU homeodomain regions are necessary for DNA-binding activity and transcriptional repression.|||The polyhistidine motif acts as a targeting signal to nuclear speckles.|||Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells (PubMed:7904822, PubMed:8995448, PubMed:8972215, PubMed:10357904, PubMed:10414983, PubMed:11163266, PubMed:17668438, PubMed:25775587). Functions either as activator or repressor by modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner (PubMed:7904822, PubMed:7935408, PubMed:8065921, PubMed:7852360, PubMed:7797498, PubMed:8662774, PubMed:9694219, PubMed:10526314, PubMed:15733064, PubMed:17145718, PubMed:18368538). Binds to the consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of promoter of target genes (PubMed:7904822, PubMed:8290353, PubMed:9111308, PubMed:10414983, PubMed:16152597, PubMed:17668438, PubMed:24643061). Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation (PubMed:8632990, PubMed:10357904, PubMed:25775587). Binds to an octamer site to form a ternary complex with ISL1; cooperates positively with ISL1 and ISL2 to potentiate transcriptional activation of RGC target genes being involved in RGC fate commitment in the developing retina and RGC axon formation and pathfinding (PubMed:8995448, PubMed:9261145, PubMed:8972215, PubMed:10357904, PubMed:11163266, PubMed:24643061, PubMed:25775587). Inhibits DLX1 and DLX2 transcriptional activities preventing DLX1- and DLX2-mediated ability to promote amacrine cell fate specification (PubMed:21875655). In cooperation with TP53 potentiates transcriptional activation of BAX promoter activity increasing neuronal cell apoptosis (PubMed:17145718). Negatively regulates BAX promoter activity in the absence of TP53 (PubMed:17145718). Acts as a transcriptional coactivator via its interaction with the transcription factor ESR1 by enhancing its effect on estrogen response element (ERE)-containing promoter (PubMed:9448000). Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to an octamer motif (PubMed:7935408, PubMed:8065921, PubMed:8537352, PubMed:7852360, PubMed:8662774). Involved in TNFSF11-mediated terminal osteoclast differentiation (PubMed:17668438).|||Up-regulated by the osteoclast differentiation factor TNFSF11 (PubMed:17668438). Down-regulated upon neuronal differentiation (PubMed:8995448). Down-regulated in presence of retinoic acid (PubMed:7904822). Down-regulated by dibutyryl cyclic AMP (PubMed:8065921).|||Weakly expressed in the dorsal root ganglion neurons at 10.5 dpc, the expression increases at least until 15.5 dpc (PubMed:22326227). Expressed in the developing ganglion cell layer of the retina at 12.5, 13.5 and 16.5 dpc (PubMed:8632990). Expressed in the outer margin of the retina at 15.5 dpc (PubMed:10414983). Expressed in embryonic heart from 13.5 dpc until birth (at protein level) (PubMed:18368538). Expressed in the developing spinal cord from 13 dpc until postnatal day 1 (PubMed:8290353, PubMed:8537352). Expressed in retinal ganglion cells (RGC) at 13.5 dpc, peaks at 15.5 dpc, declining later in development (PubMed:8637595). http://togogenome.org/gene/10090:Ctdspl2 ^@ http://purl.uniprot.org/uniprot/Q8BG15 ^@ Function|||Similarity ^@ Belongs to the CTDSPL2 family.|||Probable phosphatase. http://togogenome.org/gene/10090:Ntf3 ^@ http://purl.uniprot.org/uniprot/P20181|||http://purl.uniprot.org/uniprot/Q3V1A4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NGF-beta family.|||Brain and peripheral tissues.|||Secreted|||Seems to promote the survival of visceral and proprioceptive sensory neurons. http://togogenome.org/gene/10090:Myh2 ^@ http://purl.uniprot.org/uniprot/G3UW82 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Arpc5l ^@ http://purl.uniprot.org/uniprot/Q9D898 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ARPC5 family.|||May be a component of the Arp2/3 complex in which it may replace ARPC5.|||May function as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.|||cytoskeleton http://togogenome.org/gene/10090:Rhox2e ^@ http://purl.uniprot.org/uniprot/G3UYY0|||http://purl.uniprot.org/uniprot/Q9D4Y3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ndufa3 ^@ http://purl.uniprot.org/uniprot/Q9CQ91 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA3 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Clstn1 ^@ http://purl.uniprot.org/uniprot/Q9EPL2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As intracellular fragment AlcICD, suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1-binding.|||Belongs to the calsyntenin family.|||Directly interacts with APBA2 (PubMed:12972431). Forms a tripartite complex with APBA2 and APP (PubMed:12972431). The CTF1 chain interacts with PSEN1. Interacts with KLC1 and APBB1 (PubMed:16760430, PubMed:17332754).|||Endoplasmic reticulum membrane|||Expression in the brain gradually increases during the first postnatal week, reaching a peak at P7. In the gray matter, highly expressed in both developing and adult brain. In the white matter, at P6 highly expressed in all major fiber tracts, including the anterior commissure and the corpus callosum, as well as the external and internal capsules, while in the adult, axonal expression in fiber tracts is only faint (at protein level).|||Golgi apparatus membrane|||Highly expressed in the brain (at protein level), with over 90% of the neurons expressing detectable amounts. In the brain, relatively high levels in the cerebral cortex, striatum, hippocampus and thalamus. Moderate levels in the cerebellum. Low levels in the olfactory bulb, midbrain and pons (at protein level). Not detected in Purkinje cells. Expressed at low levels in the lung (at protein level). At the mRNA level, weakly detected in the kidney, lung, skeletal muscle, heart and testis. Not expressed in the sciatic nerve fiber.|||In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP.|||Interacts with APBB1; this interaction stabilizes AlcICD metabolism.|||Interacts with PSEN1.|||Mice lacking Clstn1, Clstn2 and Clstn3 display behavior disorders, characterized by hyperactivity in normal environment, hypersensitivity to stress, and show tendency to freeze in novel environments.|||Nucleus|||Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation (PubMed:11161476, PubMed:24613359). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with neurexin-alpha at the presynaptic membrane (By similarity). Also functions as a cargo in axonal anterograde transport by acting as a molecular adapter that promotes KLC1 association with vesicles (PubMed:17332754). Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation (PubMed:11161476, PubMed:12972431).|||Postsynaptic cell membrane|||Proteolytically processed under normal cellular conditions (PubMed:11161476, PubMed:15037614). A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1) (PubMed:11161476, PubMed:15037614). A secondary cleavage catalyzed by presenilin gamma-secretase within the transmembrane domain releases the beta-Alc-alpha chain in the extracellular milieu and produces an intracellular fragment (AlcICD) (PubMed:11161476, PubMed:15037614). Beta-Alc-alpha secretion is largely dependent upon PSEN1 and PSEN2 (PubMed:11161476, PubMed:15037614). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1 (PubMed:11161476, PubMed:15037614).|||The cytoplasmic domain binds synaptic Ca(2+).|||Vesicle|||neuron projection http://togogenome.org/gene/10090:Mical3 ^@ http://purl.uniprot.org/uniprot/Q8CJ19 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mical family.|||Cytoplasm|||Interacts with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B is of low affinity compared to other Rab proteins; at least in case of RAB8A can bind 2 molecules of RAB8A simultaneously through a high and a low affinity binding site, respectively. Interacts with ERC1 and RAB8A; may bridge ERC1 with RAB8A. Interacts with KIF23 and ERC1; enhances the interaction between KIF23 and ERC1. Interacts with NINL.|||Midbody|||Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and play a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission.|||Nucleus|||The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms).|||cell cortex|||cilium basal body|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Hs1bp3 ^@ http://purl.uniprot.org/uniprot/Q3TC93 ^@ Function|||Subunit|||Tissue Specificity ^@ Binds HCLS1. Interacts with the SH3 domain of HCLS1 in vitro.|||May be a modulator of IL-2 signaling.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Ctsz ^@ http://purl.uniprot.org/uniprot/Q545I6|||http://purl.uniprot.org/uniprot/Q9WUU7 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Exhibits carboxy-monopeptidase as well as carboxy-dipeptidase activity (By similarity). Capable of producing kinin potentiating peptides (By similarity).|||Lysosome|||The disulfide bridge formed between Cys-35 in the propeptide and the active site residue Cys-94 may prevent activation of the zymogen through formation of a reversible covalent bond with the active site residue.|||Ubiquitous. http://togogenome.org/gene/10090:Emilin3 ^@ http://purl.uniprot.org/uniprot/P59900 ^@ Developmental Stage|||Subcellular Location Annotation ^@ At 9.5 dpc, expression is only observed in the tailbud and the hindgut. At 11.5 dpc the expression is found at sites of bone formation, i.e. surrounding mesenchymal condensates in the fore- and hindlimbs, the nose, the maxilla, and the other parts of the jaw. At 13.5 dpc, detected in perichondrium and around developing skeletons, but barely detectable in mature osteoblasts. At 14.5 dpc it is strongly expressed in the enteric nerves of the digestive tract and the bladder. Expression is also observed surrounding the main branches of the alveoli and surrounding sites of bone formation in skull and trunk.|||Cytoplasm|||extracellular matrix http://togogenome.org/gene/10090:Ninj1 ^@ http://purl.uniprot.org/uniprot/O70131|||http://purl.uniprot.org/uniprot/Q3TXT8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ninjurin family.|||By nerve injury (PubMed:9465296). Expression is activated by p53/TP53 (PubMed:23690620).|||Cell membrane|||Cleaved by MMP9 protease to generate the Secreted ninjurin-1 form.|||Composed of 4 alpha helices: 2 hydrophobic transmembrane regions (alpha3 and alpha4) and 2 alpha helices (alpha1 and alpha2). Alpha1 and alpha2 feature one hydrophobic side and a hydrophilic side. In normal conditions, NINJ1 is inactivated and alpha1 and alpha2 helices are not inserted into the membrane. Following NINJ1 activation, alpha1 and alpha2 helices insert into the membrane and drive NINJ1 oligomerization via interactions between alpha3 and alpha4 and the hydrophobic face of alpha1 from an adjacent subunit. Such structures disrupt membrane integrity and form a lesion through the introduction of the hydrophilic faces of alpha1 and alpha2 into the hydrophobic membrane.|||Effector of necroptotic and pyroptotic programmed cell death that mediates plasma membrane rupture (cytolysis) (PubMed:19557008, PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476). Acts downstream of Gasdermin (GSDMA, GSDMB, GSDMC, GSDMD, or GSDME) or MLKL during pyroptosis or necroptosis, respectively: oligomerizes in response to death stimuli and promotes plasma membrane rupture by introducing hydrophilic faces of 2 alpha helices into the hydrophobic membrane, leading to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (PubMed:33472215, PubMed:37196676, PubMed:37198476). Acts as a regulator of Toll-like receptor 4 (TLR4) signaling triggered by lipopolysaccharide (LPS) during systemic inflammation; directly binds LPS (PubMed:25860173). Involved in leukocyte migration during inflammation by promoting transendothelial migration of macrophages via homotypic binding (PubMed:24917672). Promotes the migration of monocytes across the brain endothelium to central nervous system inflammatory lesions (By similarity). Also acts as a homophilic transmembrane adhesion molecule involved in various processes such as axonal growth, cell chemotaxis and angiogenesis (PubMed:24347169, PubMed:24917672, PubMed:31526566). Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM) (PubMed:24917672, PubMed:30510259). Involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells (PubMed:24917672, PubMed:30510259). Plays a role in nerve regeneration by promoting maturation of Schwann cells (PubMed:31526566). Acts as a regulator of angiogenesis (PubMed:25766274, PubMed:30354207). Promotes the formation of new vessels by mediating the interaction between capillary pericyte cells and endothelial cells (PubMed:25766274, PubMed:30354207). Also mediates vascular functions in penile tissue as well as vascular formation (PubMed:24979788). Promotes osteoclasts development by enhancing the survival of prefusion osteoclasts (PubMed:30700695). Also involved in striated muscle growth and differentiation (PubMed:31091274). Also involved in cell senescence in a p53/TP53 manner, possibly by acting as an indirect regulator of p53/TP53 mRNA translation (PubMed:23690620, PubMed:29073078).|||Homooligomer; in response to death stimuli, homooligomerizes into long, highly branched filaments and large, ring-shaped structures in the membrane.|||In normal conditions, NINJ1 is inactivated. In response to death stimuli, homooligomerizes and disrupts membrane integrity by introducing the hydrophilic faces of alpha1 and alpha2 helices into the hydrophobic membrane (By similarity). Homooligomerization and ability to mediate plasma membrane rupture is inhibited by glycine; it is unclear whether glycine directly or indirectly inhibits homooligomerization (PubMed:36468682).|||Membrane|||N-linked glycosylation is required for homooligomerization.|||No visible phenotype in most cases (PubMed:24347169, PubMed:27815839). Some mice have dome-shaped heads and die within 2 months after birth (PubMed:27815839). Mice show abnormal behavior, reminiscent of obsessive-compulsive disorder: mice exhibit compulsive grooming-induced hair loss and self-made lesions as well as increased anxiety-like behaviors (PubMed:27815839). Mice are prone to systemic chronic inflammation in the skin, liver, kidney and pancreas (PubMed:29073078). During inflammation, reduced motility of bone marrow-derived macrophages and protrusive membrane dynamics are observed (PubMed:24917672). Mice also display attenuated susceptibility to experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis: attenuated susceptibility is caused by reduced leukocyte infiltration and decreased adherence of leukocytes on retinal vessels (PubMed:27815839). Abolished ability to mediate plasma membrane rupture downstream cell death, without affecting GSDMD pore formation (PubMed:33472215). Conditional deletion in pericytes impairs vessel maturation and blood flow recovery in hind limb ischemia (PubMed:30354207).|||Secreted|||Secreted form generated by cleavage, which has chemotactic activity (PubMed:23142597). Acts as an anti-inflammatory mediator by promoting monocyte recruitment, thereby ameliorating atherosclerosis (PubMed:32883094).|||Synaptic cell membrane http://togogenome.org/gene/10090:Dars ^@ http://purl.uniprot.org/uniprot/Q922B2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family. Type 2 subfamily.|||Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.|||Cytoplasm|||Homodimer (By similarity). Part of a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:12060739). http://togogenome.org/gene/10090:Spidr ^@ http://purl.uniprot.org/uniprot/Q8BGX7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts (via C-terminal region) with BLM; the interaction is direct. Interacts with RAD51; the interaction is direct. Interacts (via the C-terminal region) with FIGNL1 (via N-terminal one-half region); the interaction is direct (By similarity).|||Nucleus|||Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR). Serves as a scaffolding protein that helps to promote the recruitment of DNA-processing enzymes like the helicase BLM and recombinase RAD51 to site of DNA damage, and hence contributes to maintain genomic integrity (By similarity). http://togogenome.org/gene/10090:Pik3cb ^@ http://purl.uniprot.org/uniprot/Q8BTI9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylation at Ser-1064 negatively regulates the phosphatidylinositol-4,5-bisphosphate 3-kinase activity.|||Belongs to the PI3/PI4-kinase family.|||Cytoplasm|||Heterodimer of a catalytic subunit PIK3CB and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required for nuclear localization and nuclear export (By similarity). Part of a complex with PIK3R1 and PTEN (By similarity). Binding to PTEN may antagonize the lipid kinase activity under normal growth conditions (By similarity). Part of a complex involved in autophagosome formation composed of PIK3C3 and PIK3R4. Interacts with BECN1, ATG14 and RAB5A.|||Mice have defects in autophagosome formation. Have normal bleeding time but are resistant to thrombosis after arterial injury. Mice fail to induce tumors in a model of prostate tumor formation induced by Pten loss.|||Nucleus|||Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. Has also a protein kinase activity showing autophosphorylation.|||Phosphorylation at Ser-1064 down-regulates lipid kinase activity.|||The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival (By similarity). http://togogenome.org/gene/10090:AU021092 ^@ http://purl.uniprot.org/uniprot/Q3UST5 ^@ Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UPF0764 family.|||From embryonic day (E) 17.5 onward in the developing mouse thyroid and lung.|||Glycosylated.|||Homodimer.|||Predominantly expressed in thyroid tissue.|||Secreted http://togogenome.org/gene/10090:Ltk ^@ http://purl.uniprot.org/uniprot/P08923|||http://purl.uniprot.org/uniprot/Q0VGZ5 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by ligand-binding, leading to homodimerization and autophosphorylation.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Endoplasmic reticulum|||Homodimer; homodimerizes following ligand-binding. Part of a complex including LTK, TNK2 and GRB2, in which GRB2 promotes LTK recruitment by TNK2.|||May be produced by alternative promoter usage.|||May be produced by alternative promoter usage. Starts at a CUG codon.|||Mice do not show any decrease in newborn neurons (PubMed:22079349). Mice lacking both Alk and Ltk show a strong reduction in newborn neurons (PubMed:22079349).|||Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.|||Receptor with a tyrosine-protein kinase activity. Following activation by ALKAL1 or ALKAL2 ligands at the cell surface, transduces an extracellular signal into an intracellular response. Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (By similarity). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (By similarity). The exact function of this protein is not known; studies with chimeric proteins demonstrate its ability to promote growth and specifically neurite outgrowth, and cell survival. Involved in regulation of the secretory pathway involving endoplasmic reticulum (ER) export sites (ERESs) and ER to Golgi transport (By similarity).|||Subsets of lymphoid and neuronal cells. http://togogenome.org/gene/10090:Cacna2d3 ^@ http://purl.uniprot.org/uniprot/A0A411ACY3|||http://purl.uniprot.org/uniprot/Q9Z1L5 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel subunit alpha-2/delta family.|||Brain-specific. Predominantly expressed in the caudate putamen, entorhinal complex, hippocampus and cortex.|||Dimer formed of alpha-2-2 and delta-2 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (By similarity).|||In contrast to CACNA2D1 and CACNA2D2, it does not bind gabapentin, an antiepileptic drug.|||May be proteolytically processed into subunits alpha-2-3 and delta-3 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role.|||Membrane|||N-glycosylated.|||The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.|||The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) but not T-type (CACNA1G). http://togogenome.org/gene/10090:Aldh3a2 ^@ http://purl.uniprot.org/uniprot/B1AV77|||http://purl.uniprot.org/uniprot/P47740 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldehyde dehydrogenase family.|||Catalyzes the oxidation of medium and long-chain aliphatic aldehydes to fatty acids. Active on a variety of saturated and unsaturated aliphatic aldehydes between 6 and 24 carbons in length (PubMed:25286108). Responsible for conversion of the sphingosine 1-phosphate (S1P) degradation product hexadecenal to hexadecenoic acid (PubMed:25286108).|||Endoplasmic reticulum membrane|||Homodimer.|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Lgals3bp ^@ http://purl.uniprot.org/uniprot/Q07797 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in embryo, liver, spleen, kidney, lung, heart, intestine, thymus and lymph node.|||Homodimers and homomultimers. The multimers form ring-like structures with a diameter of 30-40 nm. Binds LGALS1 and LGALS3. Binds ITGB1, COL4A1, COL5A1, COL6A1, FN1 and NID (By similarity). Interacts with PPIC (in vitro). The unglycosylated form interacts with PDE4DIP isoform 2/MMG8/SMYLE; this interaction may connect a pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) to promote microtubule assembly and acetylation (By similarity).|||N-glycosylated.|||Promotes integrin-mediated cell adhesion. May stimulate host defense against viruses and tumor cells (By similarity).|||Secreted|||Up-regulated by TNF and IFNG.|||extracellular matrix http://togogenome.org/gene/10090:Or4a81 ^@ http://purl.uniprot.org/uniprot/Q8VFB1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tinagl1 ^@ http://purl.uniprot.org/uniprot/Q99JR5 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Down-regulated in prostate after castration.|||Glycosylated.|||Highly expressed in kidney, heart and adrenocortical cells of adrenal glands. Moderately expressed in spleen and liver. Also found in prostate, seminal vesicle, epididymis and testis in male reproductive organs. In adrenal glands is found in the outer cortical regions corresponding to the zona glomerulosa (zG) and the undifferentiated cell zone (zU) (at protein level).|||May be implicated in the adrenocortical zonation and in mechanisms for repressing the CYP11B1 gene expression in adrenocortical cells. This is a non catalytic peptidase C1 family protein.|||Secreted http://togogenome.org/gene/10090:Haus4 ^@ http://purl.uniprot.org/uniprot/Q8BFT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS4 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||centrosome|||spindle http://togogenome.org/gene/10090:Or14j7 ^@ http://purl.uniprot.org/uniprot/Q7TRJ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Speg ^@ http://purl.uniprot.org/uniprot/E9QQ25|||http://purl.uniprot.org/uniprot/Q62407 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Expression is under the tight control of the locus control region (LCRs).|||Interacts with MTM1 (By similarity). Isoform 3 is found as a monomer or homodimer.|||Isoform 1 is preferentially expressed in striated muscle. Non-kinase form such as isoform 3 is predominantly expressed in the aorta. Isoform 3 appears to be expressed only in highly differentiated ASMC in normal vessel walls and down-regulated in dedifferentiated ASMC in vivo. In response to vascular injuries ASMC dedifferentiate and change from a quiescent and contractile phenotype to a proliferative and synthetic phenotype. This proliferation of vascular smooth muscle cells is one of the most prominent features of atherosclerosis. Isoform 1 and isoform 4 are expressed in cardiomyocytes of the developing heart.|||Isoform 3 is quickly down-regulated in response to vascular injury, when ASMC cells change from a quiescent to a proliferative phenotype.|||Isoform 3 may have a role in regulating the growth and differentiation of arterial smooth muscle cells.|||May be autophosphorylated.|||Mice lacking SPEG demonstrate dilation of right and left atria and ventricles, cardiac hypertrophy, myofibril degeneration, and a marked decrease in cardiac function. Moreover, mutant mice exhibit significant neonatal mortality.|||Nucleus|||Produced by alternative promoter usage. http://togogenome.org/gene/10090:Ramp1 ^@ http://purl.uniprot.org/uniprot/A0A087WPC6|||http://purl.uniprot.org/uniprot/E9Q915|||http://purl.uniprot.org/uniprot/Q3TNJ3|||http://purl.uniprot.org/uniprot/Q9WTJ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RAMP family.|||Expressed predominantly in the thymus, skeletal muscle, embryonic and adult brain, embryonic and adult lung, and colon.|||Heterodimer of CALCRL and RAMP1.|||Membrane|||Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL. http://togogenome.org/gene/10090:Hoxb3 ^@ http://purl.uniprot.org/uniprot/P09026 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Gdf3 ^@ http://purl.uniprot.org/uniprot/Q07104 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Cytoplasm|||Embryonic lethality in one-third of the mutant embryos because of pregastrulation developmental malformations. However, the majority of mutants survive until adulthood without any overt abnormality (PubMed:17936261, PubMed:16368929). Mutant mice shown resistance to diet-induced obesity (PubMed:18480259).|||Growth factor involved in early embryonic development and adipose-tissue homeostasis. During embryogenesis controls formation of anterior visceral endoderm and mesoderm and the establishment of anterior-posterior identity through a receptor complex comprising the receptor ACVR1B and the coreceptor CRIPTO (PubMed:16368929, PubMed:17936261). Regulates adipose-tissue homeostasis and energy balance under nutrient overload in part by signaling through the receptor complex based on ACVR1C and CRIPTO.|||Homodimer. Heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.|||In contrast to other members of this family, cannot be disulfide-linked due to an atypical cysteine knot configuration, where the fourth cysteine is missing. This fourth cysteine is involved in an inter-molecular bridge to stabilize the active form of homodimeric or heterodimeric signaling molecules.|||Markedly increased in an obese-mouse model lacking adipocyte fatty acid-binding protein FABP4.|||Primarily in adult bone marrow, spleen, thymus and adipose tissue.|||Secreted|||Synthesized as large precursor molecule that undergo proteolytic cleavage, releasing the pro-domain from the active, receptor binding, C-terminal region of the molecule. http://togogenome.org/gene/10090:Vmn1r172 ^@ http://purl.uniprot.org/uniprot/Q9EPS4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tor3a ^@ http://purl.uniprot.org/uniprot/Q9ER38 ^@ Developmental Stage|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 16 dpc, widely expressed with very low levels in heart, liver and neural tissues.|||Belongs to the ClpA/ClpB family. Torsin subfamily.|||By interferon-alpha and interferon-gamma, in spleen and liver.|||Cytoplasm|||Endoplasmic reticulum lumen|||Interacts with TOR1AIP1.|||N-glycosylated. http://togogenome.org/gene/10090:Dop1b ^@ http://purl.uniprot.org/uniprot/Q3UHQ6|||http://purl.uniprot.org/uniprot/Q9DCG4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dopey family.|||Early endosome membrane|||Expressed in liver, heart and brain.|||Golgi apparatus membrane|||Highly expressed in developing nervous system.|||Homooligomer. Heterotrimer with ATP9A and MON2; this interaction is retromer-independent. Interacts with SNX3.|||May play a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and MON2, regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation. http://togogenome.org/gene/10090:Arl2 ^@ http://purl.uniprot.org/uniprot/Q9D0J4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Arf family.|||Cytoplasm|||Expressed in brain, lung, cerebellum, liver, kidney, hippocampus, spleen, cortex and heart (at protein level).|||Found in a complex with ARL2, ARL2BP and SLC25A6. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with ELMOD2. The GTP-bound form interacts with ARL2BP. Interacts with TBCD; the GDP-bound form interacts preferentially with TBCD. Interacts with UNC119 (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4. The GTP-bound form interacts with PDE6D.|||Mitochondrion intermembrane space|||Not N-myristoylated.|||Nucleus|||Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle.|||centrosome http://togogenome.org/gene/10090:Clca3a2 ^@ http://purl.uniprot.org/uniprot/Q9EQR4 ^@ Similarity ^@ Belongs to the CLCR family. http://togogenome.org/gene/10090:Elapor2 ^@ http://purl.uniprot.org/uniprot/B9EHI9|||http://purl.uniprot.org/uniprot/Q3UZV7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ELAPOR family.|||Cell membrane|||Functions as a regulator of the BMP signaling pathway and may be involved in epidermal differentiation.|||Membrane http://togogenome.org/gene/10090:Ppig ^@ http://purl.uniprot.org/uniprot/A2AR02 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Inhibited by cyclosporin A (CsA).|||Interacts with CLK1, PNN and with the phosphorylated C-terminal domain of RNA polymerase II.|||Nucleus matrix|||Nucleus speckle|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. May be implicated in the folding, transport, and assembly of proteins. May play an important role in the regulation of pre-mRNA splicing.|||The RS domain is required for the interaction with the phosphorylated C-terminal domain of RNA polymerase II. http://togogenome.org/gene/10090:Usp9x ^@ http://purl.uniprot.org/uniprot/P70398|||http://purl.uniprot.org/uniprot/Q4FE56 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At least expressed from 17 dpc to 21 postnatal days.|||Belongs to the peptidase C19 family.|||Brain-specific USP9X deletion results in early postnatal death, whereas forebrain-specific deletion is compatible with survival to adulthood. In the absence of USP9X the cortical architecture is disorganized, and neurons display reduced neurite growth.|||Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (PubMed:29626158, PubMed:30951545). May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin (PubMed:29626158, PubMed:30951545). Specifically hydrolyzes 'Lys-63'-, 'Lys-48'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitins chains (By similarity). Essential component of TGF-beta/BMP signaling cascade (By similarity). Specifically deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33 (By similarity). Deubiquitinates alkylation repair enzyme ALKBH3 (By similarity). OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (By similarity). Deubiquitinates mTORC2 complex component RICTOR at 'Lys-294' by removing 'Lys-63'-linked polyubiquitin chains, stabilizing RICTOR and enhancing its binding to MTOR, thus promoting mTORC2 complex assembly (By similarity). Regulates chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres (By similarity). Involved in axonal growth and neuronal cell migration (PubMed:24607389). Regulates cellular clock function by enhancing the protein stability and transcriptional activity of the core circadian protein BMAL1 via its deubiquitinating activity (PubMed:29626158). Acts as a regulator of peroxisome import by mediating deubiquitination of PEX5: specifically deubiquitinates PEX5 monoubiquitinated at 'Cys-11' following its retrotranslocation into the cytosol, resetting PEX5 for a subsequent import cycle (By similarity). Deubiquitinates PEG10 (PubMed:30951545).|||Highest levels in liver and brain with expression also detected in heart, muscle, spleen and kidney (at protein leve) (PubMed:33378666). Ubiquitously expressed in adult tissues (PubMed:9178254).|||Interacts with SMAD4, MARK4, NUAK1 and BIRC5/survivin. Interacts with DCX. Interacts with OTUD4 and USP7; the interaction is direct (By similarity).|||cilium axoneme|||cytosol|||growth cone http://togogenome.org/gene/10090:Sorbs2 ^@ http://purl.uniprot.org/uniprot/Q3UTJ2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that plays a role in the assembling of signaling complexes, being a link between ABL kinases and actin cytoskeleton. Can form complex with ABL1 and CBL, thus promoting ubiquitination and degradation of ABL1 (By similarity). May play a role in the regulation of pancreatic cell adhesion, possibly by acting on WASF1 phosphorylation, enhancing phosphorylation by ABL1, as well as dephosphorylation by PTPN12 (By similarity).|||Apical cell membrane|||Interacts with ABL, CBL, DNM1, DNM2, FLOT1, AFDN, PTK2B/PYK2, SAPAP, SPTAN1, SYNJ1, SYNJ2, VCL/vinculin, WASF, ABL1/c-Abl, ABL2/v-Abl/Arg, ACTN, CBL and PALLD. Interacts with PTPN12 and WASF1 via its SH3 domains; this interaction may mediate the partial PTPN12 and WASF1 translocation to focal adhesion sites.|||The first 2 SH3 domains are required for WASF1-binding. All 3 SH3 domains can bind independently to PTPN12.|||Ubiquitinated by CBL.|||Z line|||cytoskeleton|||focal adhesion|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Gpbar1 ^@ http://purl.uniprot.org/uniprot/Q14AA9|||http://purl.uniprot.org/uniprot/Q80SS6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids (By similarity). Involved in bile acid promoted GLP1R secretion. http://togogenome.org/gene/10090:Kdsr ^@ http://purl.uniprot.org/uniprot/Q6GV12|||http://purl.uniprot.org/uniprot/Q8CII3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the reduction of 3-ketodihydrosphingosine (KDS) to dihydrosphingosine (DHS).|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Sprtn ^@ http://purl.uniprot.org/uniprot/G3X912 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated following deubiquitination by VCPIP1, leading to recruitment to chromatin and DNA damage sites.|||Autocatalytically cleaved in response to double-stranded DNA-binding: autocatalytic cleavage takes place in trans and leads to inactivation.|||Belongs to the Spartan family.|||Chromosome|||DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation.|||DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:28199696, PubMed:27871365). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:28199696, PubMed:27871365). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis. Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (By similarity). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs. SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). Involved in recruitment of VCP/p97 to sites of DNA damage. Also acts as an activator of CHEK1 during normal DNA replication by mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from chromatin and subsequent activation. Does not activate CHEK1 in response to DNA damage. May also act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis (By similarity).|||Embryonic lethality caused by genomic instability (PubMed:25501849). Cells display impaired lesion bypass, incomplete DNA replication, formation of micronuclei and chromatin bridges and eventually cell death (PubMed:25501849). Cells show an accumulation of DNA-protein cross-links (DPCs) (PubMed:28199696). Sprtn-haploinsufficient mice are viable but show accelerated aging, characterized by cataracts, lordokyphosis and cachexia at a young age (PubMed:25501849).|||Homodimer. Interacts (VIA PIP-box) with PCNA (when ubiquitinated). Interacts (via its SHP-box) with VCP/p97. Interacts with RAD18. Interacts with KCTD13 and POLD3.|||Monoubiquitinated; monoubiquitination promotes exclusion from chromatin. Deubiquitinated by VCPIP1: deubiquitination is required for subsequent acetylation and recruitment to chromatin and DNA damage sites.|||Nucleus|||Phosphorylation by CHEK1 promotes recruitment to chromatin.|||The PIP-box mediates the interaction with PCNA, while the UBZ4-type zinc finger mediates binding to 'Lys-48'- and 'Lys-63'-linked polyubiquitin. http://togogenome.org/gene/10090:Or8g19 ^@ http://purl.uniprot.org/uniprot/Q9EQ90 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tcerg1 ^@ http://purl.uniprot.org/uniprot/Q8CGF7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds RNA polymerase II, HD and SF1 (By similarity). Binds formin. Interacts (via the second WW domain) with TREX1 (via proline-rich region).|||Nucleus|||The FF domains preferentially binds peptides with the consensus sequence [DE](2-5)-[FWY]-[DE](2-5) and mediate interaction with HTATSF1 and probably bind the phosphorylated C-terminus of the largest subunit of RNA polymerase II.|||The WW domains bind Pro-rich domains.|||Transcription factor that binds RNA polymerase II and inhibits the elongation of transcripts from target promoters. Regulates transcription elongation in a TATA box-dependent manner (By similarity). http://togogenome.org/gene/10090:Jcad ^@ http://purl.uniprot.org/uniprot/Q5DTX6 ^@ Subcellular Location Annotation ^@ adherens junction http://togogenome.org/gene/10090:Gabrr3 ^@ http://purl.uniprot.org/uniprot/B2RXA8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Or5k15 ^@ http://purl.uniprot.org/uniprot/E9Q9T3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Map3k14 ^@ http://purl.uniprot.org/uniprot/Q544K4|||http://purl.uniprot.org/uniprot/Q9WUL6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cytoplasm|||Interacts with TRAF2, TRAF3, TRAF5, TRAF6, IKKA and NF-kappa-B2/P100. Interacts with PELI3. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with ZFP91 (By similarity). Interacts with NLRP12; this interaction promotes proteasomal degradation of MAP3K14. Directly interacts with DDX3X (By similarity). Interacts (via C-terminus and kinase domain) with PPPC3A (via N-terminus) and PPP3CB (PubMed:26029823).|||Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity.|||Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.|||Mice display the alymphoplasia phenotype (aly), which is characterized by systemic absence of lymph nodes and Peyer patches and disorganized splenic and thymic structures with immunodeficiency.|||Phosphorylation at Thr-561 is required to activates its kinase activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization (By similarity). Autophosphorylated.|||Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. 'Lys-48'-linked polyubiquitination leads to its degradation by the proteasome, while 'Lys-63'-linked polyubiquitination stabilizes and activates it (By similarity). http://togogenome.org/gene/10090:Chrng ^@ http://purl.uniprot.org/uniprot/F8VQK4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Dbt ^@ http://purl.uniprot.org/uniprot/P53395 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2-oxoacid dehydrogenase family.|||Binds 1 lipoyl cofactor covalently.|||Forms a 24-polypeptide structural core with octahedral symmetry.|||Mitochondrion matrix|||The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component. http://togogenome.org/gene/10090:Fdxr ^@ http://purl.uniprot.org/uniprot/Q61578 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ferredoxin--NADP reductase type 1 family.|||Expressed in the adrenal, testis and ovary and to a lesser extent in the liver and kidney.|||Mitochondrion inner membrane|||Monomer. Interacts directly with FDX1.|||Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver. http://togogenome.org/gene/10090:Ascl2 ^@ http://purl.uniprot.org/uniprot/O35885 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both maternal and embryonic transcription (PubMed:9622625). Transcribed from both the maternal and paternal genome, at least in eight-cell stage, late morula and blastocyst (PubMed:9622625). Expressed during all stages of oogenesis, from immature oocyte to mature oocytes in the antral follicles (PubMed:9622625). Expressed at low level in late two-cell stage (49 h) zygote, increasing slightly between the late two-cell stage and the eight-cell stage (77 h), then increasing dramatically by about 10-fold at the morula stage (88 hours) (PubMed:9622625). Early egg cylinder stage embryos, at 5.5 days post coitum (dpc) show strong expression throughout the diploid ectoplacental cone (EPC) and the extraembryonic ectoderm, but no expression in the giant cells or the embryonic ectoderm or primitive endoderm (PubMed:9622625). Expressed transiently at 7.5-8.5 dpc at low levels in the embryo (PubMed:8090202). Expressed at 7.5-8.5 dpc at high levels in extra-embryonic tissues, the chorion and the EPC, but not detectable in secondary giant cells or the allantois (PubMed:8090202, PubMed:9622625, PubMed:10611232). At 9.5-10.5 dpc, expression persists in both the labyrinthine layer and the outer spongiotrophoblast layer of the placenta, with stronger expression in the spongiotrophoblast (PubMed:9622625). By 12.5 dpc, expression in the spongiotrophoblast layer is restricted to only a subset of cells (PubMed:10611232). Overall expression in the placental layers declines after 10 dpc, declining further by 15.5 dpc (PubMed:9622625).|||Efficient DNA binding requires dimerization with another basic helix-loop-helix (bHLH) protein (PubMed:10611232). Forms heterodimers with bHLH transcription factor TCF3 (PubMed:10611232). May not heterodimerise with bHLH protein HAND1 (PubMed:10611232).|||Embryonic lethality between 9.5 and 10.5 days post coitum (dpc) (PubMed:8090202, PubMed:7773285). Abnormalities in extraembryonic trophoblast cell types; by 8.5 dpc, the ectoplacental cone (EPC) lacks diploid precursors and by 9.5-10.5 dpc, the spongiotrophoblast layer of the placenta is missing and the labyrinthine layer lacks normal highly vascularized organization (PubMed:8090202, PubMed:7773285). Unexpectedly, does not exacerbate trophoblast phenotype at 8.5 dpc when combined with simultaneous knockout of basic helix-loop-helix transcription factor HAND1 (PubMed:10611232). Conditional knockout targeted at cells expressing T-cell surface glycoprotein CD4 causes loss of body weight from day 3 to day 9 after influenza infection; 5-fold higher levels of viral hemagglutinin mRNA in lungs, by comparison with controls (PubMed:24463518). Lung-draining lymph nodes contain less than half normal level of follicular T-helper (Tfh) cells (PubMed:24463518). Development of Tfh cells and germinal center B-cells is reduced in the spleen (PubMed:24463518). Increased expression of TCF3/E47 in Tfh and naive T-cells (PubMed:24463518).|||Expressed in follicular T-helper (Tfh) cells.|||Nucleus|||The ASCL2 locus is imprinted in mice (PubMed:7773285). Maternal inherited gene is expressed, while the paternal inherited gene is imprinted, hence silenced (PubMed:7773285). However, the paternal gene is expressed in some trophoblast cells in early postimplantation embryonic stages and almost completely extinguished by 8.5 days post coitum (dpc) (PubMed:7773285).|||Transcription factor (PubMed:10611232, PubMed:29500235). Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3 (PubMed:10611232, PubMed:29500235). May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes (PubMed:29500235). Required during post-implantation development for the generation of some differentiated trophoblast cell types (PubMed:8090202). Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins (PubMed:10611232). Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6 (PubMed:24463518). May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation (PubMed:24463518). Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin (PubMed:25620640). May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R-spondin signaling, and thereby maintaining stem cell characteristics (PubMed:25620640). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up-regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells (By similarity). May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (By similarity). May be dispensable for blastocyst formation and later embryonic function (PubMed:8090202, PubMed:9622625). May be involved in the determination of neuronal precursors (By similarity).|||Up-regulated in activated T-cells after immunization. http://togogenome.org/gene/10090:Uhrf1 ^@ http://purl.uniprot.org/uniprot/Q8VDF2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in thymus, testis, spleen and lung. Within testis, expressed in almost all cells except elongated spermatids.|||Interacts with DNMT3A and DNMT3B. Interacts with DNMT1; the interaction is direct. Interacts with USP7; leading to its deubiquitination. Interacts with HDAC1, but not with HDAC2. Interacts with BLTP3A. Interacts with PML. Interacts with EHMT2. Binds hemimethylated CpG containing oligonucleotides (PubMed:15361834, PubMed:17994007, PubMed:18772888, PubMed:18772891, PubMed:19056828, PubMed:19798101, PubMed:21268065). Interacts with PRAMEL7 (PubMed:28604677). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). Interacts with UHRF2 (By similarity). Interacts with FANCD2 (By similarity). Interacts with TET1 isoform 2; this interaction induces the recruitment of TET1 isoform 2 to replicating heterochromatin (PubMed:36056023).|||Mice display a sensitization to DNA damage and replication block, and die in mid-gestation.|||Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF1 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation.|||Nucleus|||Phosphorylation at Ser-303 of the linker region decreases the binding to H3K9me3. Phosphorylation at Ser-639 by CDK1 during M phase impairs interaction with USP7, preventing deubiquitination and leading to degradation by the proteasome (By similarity).|||The RING finger is required for ubiquitin ligase activity.|||The YDG domain (also named SRA domain) specifically recognizes and binds hemimethylated DNA at replication forks (DNA that is only methylated on the mother strand of replicating DNA) (PubMed:17994007). The YDG domain contains a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. 2 specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other 3 bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand (PubMed:18772888). The YDG domain also recognizes and binds 5-hydroxymethylcytosine (5hmC).|||The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3). The tudor-like regions simultaneously recognizes H3K9me3 through a conserved aromatic cage in the first tudor-like subdomain and unmodified H3K4 (H3K4me0) within a groove between the tandem subdomains (PubMed:21489993). The linker region plays a role in the formation of a histone H3-binding hole between the reader modules formed by the tudor-like regions and the PHD-type zinc finger by making extended contacts with the tandem tudor-like regions.|||Ubiquitinated; which leads to proteasomal degradation. Autoubiquitinated; interaction with USP7 leads to deubiquitination and prevents degradation. Ubiquitination and degradation takes place during M phase, when phosphorylation at Ser-639 prevents interaction with USP7 and subsequent deubiquitination. Polyubiquitination may be stimulated by DNA damage.|||Up-regulated in proliferating cells, and down-regulated in quiescent or differentiated cells. Early induced by E1A in postmitotic cells. Down-regulated by aphidicolin. http://togogenome.org/gene/10090:Chic1 ^@ http://purl.uniprot.org/uniprot/Q8CBW7 ^@ Caution|||Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CHIC family.|||Cell membrane|||Cytoplasmic vesicle|||Detected in the 7, 11, 15, or 19 dpc.|||Expressed moderately in the brain.|||It is uncertain whether Met-1 or Met-8 is the initiator.|||Palmitoylated. http://togogenome.org/gene/10090:Gstt2 ^@ http://purl.uniprot.org/uniprot/Q61133 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Theta family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Homodimer.|||In liver, highest expression found in central vein limiting plate hepatocytes. Also expressed in interlobular bile duct epithelial cells. In lung, expressed in club cells and ciliated cells of the bronchiolar epithelium and in type II alveolar cells of the lung parenchyma.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Nipa1 ^@ http://purl.uniprot.org/uniprot/Q8BHK1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Fe(2+), Sr(2+), Ba(2+), Zn(2+) and Co(2+) but to a much less extent than Mg(2+).|||Belongs to the NIPA family.|||Cell membrane|||Early endosome|||Homodimer.|||Up-regulated by low magnesium ion levels.|||Widely expressed. Predominantly expressed in neuronal tissues. Brain, heart, kidney, liver and colon (at protein level). http://togogenome.org/gene/10090:Tceal1 ^@ http://purl.uniprot.org/uniprot/Q921P9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TFS-II family. TFA subfamily.|||May be involved in transcriptional regulation. Modulates various viral and cellular promoters in a promoter context-dependent manner. Does not bind DNA directly (By similarity).|||Nucleus http://togogenome.org/gene/10090:Rnpepl1 ^@ http://purl.uniprot.org/uniprot/G5E872 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Broad specificity aminopeptidase which preferentially hydrolyzes an N-terminal methionine, citrulline or glutamine. http://togogenome.org/gene/10090:Csnk1a1 ^@ http://purl.uniprot.org/uniprot/Q6PJ87 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Hdgf ^@ http://purl.uniprot.org/uniprot/P51859 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor (By similarity). Has mitogenic activity for fibroblasts (By similarity). Heparin-binding protein (By similarity).|||Belongs to the HDGF family.|||Cytoplasm|||Expressed predominantly in testis and skeletal muscle, to intermediate extents in heart, brain, lung, liver, and kidney, and to a minimal extent in spleen.|||Monomer, and domain-swapped homodimer (By similarity). Interacts with nuclear proteins NCL and YBX1/YB1 (By similarity).|||Nucleus|||Phosphorylation at Ser-165 is likely to be required for secretion.|||Sumoylated with SUMO1. Sumoylation prevents binding to chromatin.|||The N-terminal region does not contain a typical signal sequence but is required for secretion (PubMed:21087088). It also determines exosomal location (By similarity).|||The PWWP domain harbors the heparin-binding sites and is responsible for DNA-binding, while the C-terminal region is essentially unstructured.|||extracellular exosome http://togogenome.org/gene/10090:Dtnb ^@ http://purl.uniprot.org/uniprot/O70585|||http://purl.uniprot.org/uniprot/Q8K0N0 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basal cell membrane|||Belongs to the dystrophin family. Dystrobrevin subfamily.|||Cytoplasm|||Expressed mainly in liver and lung. Expressed in brain, namely in neurons of the cortex and hippocampus and in the dendrites, soma, and nuclei of pyramidal neurons of the hippocampus region CA1 (PubMed:11585924). Expressed in kidney, namely in epithelial cells of renal tubules, collecting ducts, Bowman's capsules and glomeruli (PubMed:10893187). Expressed in blood vessels and pia (PubMed:16540561).|||Homozygous knockout mice for Dtnb are viable and fertile, and are normal in appearance (PubMed:11585924, PubMed:16540561). Double knockout mice for DTNA and DTNB genes have a mild myopathy plus synaptic defects and abnormal motor behavior (PubMed:16540561).|||Interacts with dystrophin short form DP71 and syntrophins SNTG1 and SNTG2 (By similarity). Binds DTNBP1 (PubMed:11316798). Forms a specific complex composed of DMD, SNTB2 and SNTA1 in neuron; the interaction with SNTB2 and SNTA1 is DMD independent (PubMed:10545507). Interacts with UTRN and dystrophin short form DP71 in the kidney and liver (PubMed:10893187). Interacts with SNTB1, SNTB2 and SNTA1 in kidney and liver (PubMed:10893187). Interacts with KIF5A (PubMed:14600269, PubMed:22978324). Interacts with HMG20A and HMG20B (PubMed:20530487). Interacts with OLFM1 (PubMed:17265465). Interacts with PRKAR2B and PRKAR1A (PubMed:17610895).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Phosphorylated by PKA (PubMed:17610895). Phosphorylation at Thr-11 alters the interaction with KIF5A (PubMed:22978324).|||Postsynapse|||Postsynaptic density|||Scaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids (PubMed:11585924). May function as a repressor of the SYN1 promoter through the binding of repressor element-1 (RE-1), in turn regulates SYN1 expression and may be involved in cell proliferation regulation during the early phase of neural differentiation (PubMed:20530487). May be required for proper maturation and function of a subset of inhibitory synapses (PubMed:16540561).|||The coiled coil domain may mediate the interaction with dystrophin.|||dendrite http://togogenome.org/gene/10090:Pramel30 ^@ http://purl.uniprot.org/uniprot/L7MU96 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Trim26 ^@ http://purl.uniprot.org/uniprot/Q99PN3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinates upon viral infection. In turn, autoubiquitinated TRIM26 recruits NEMO and bridges TBK1-NEMO interaction.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs). Plays also a central role in determining the response to different forms of oxidative stress by controlling levels of DNA glycosylases NEIL1, NEIL3 and NTH1 that are involved in repair of damaged DNA. Promotes nuclear IRF3 ubiquitination and proteasomal degradation. Bridges together TBK1 and NEMO during the innate response to viral infection leading to the activation of TBK1. Positively regulates LPS-mediated inflammatory innate immune response by catalyzing the 'Lys-11'-linked polyubiquitination of TAB1 to enhance its activation and subsequent NF-kappa-B and MAPK signaling (PubMed:34017102). In a manner independent of its catalytic activity, inhibits WWP2, a SOX2-directed E3 ubiquitin ligase, and thus protects SOX2 from polyubiquitination and proteasomal degradation. Ubiquitinates the histone acetyltransferase protein complex component PHF20 and thereby triggers its degradation in the nucleus after its recruitment by the histone demethylase KDM6B, serving as a scaffold protein. Upon induction by TGF-beta, ubiquitinates the TFIID component TAF7 for proteasomal degradation (By similarity). Induces ferroptosis by ubiquitinating SLC7A11, a critical protein for lipid reactive oxygen species (ROS) scavenging (PubMed:33869196).|||Interacts with TBK1; this interaction bridges together TBK1 and NEMO in order to activate TBK1. Interacts with INCA1.|||Nucleus|||TRIM26 attenuatess the production of proinflammatory cytokines in response to TLR ligands, TNF-alpha, and IL-1beta stimulation. In addition, the challenge of TRIM26-deletion mice with LPS results in inflammatory responses that are less lethal than those in wild-type mice. http://togogenome.org/gene/10090:Phlda1 ^@ http://purl.uniprot.org/uniprot/Q62392 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic vesicle|||Induced by IGF-I.|||Interacts with RPL14, EIF3S7 and PABPC4.|||Seems to be involved in regulation of apoptosis. May be involved in detachment-mediated programmed cell death. May mediate apoptosis during neuronal development. May be involved in regulation of anti-apoptotic effects of IGF1. Required for TCR-induced apoptosis and expression of TNFRSF6/FAS in a T-cell hybridoma cell line. May be involved in translational regulation.|||Widely expressed with very high levels in adult liver and high levels in adult lung. According to PubMed:10428057 expressed at low levels in liver. Expressed at increased levels in atherosclerotic lesions observed in hyperhomocysteinema.|||nucleolus http://togogenome.org/gene/10090:Eif4b ^@ http://purl.uniprot.org/uniprot/Q8BGD9 ^@ Function|||PTM|||Subunit ^@ Phosphorylated at Ser-422 by RPS6KA1 and RPS6KB1; phosphorylation enhances the affinity of EIF4B for the EIF3 complex. In response to mTORC1 activation, RPS6KA1-mediated phosphorylation at 'Ser-406' and 'Ser-422' stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function.|||Required for the binding of mRNA to ribosomes. Functions in close association with EIF4-F and EIF4-A. Binds near the 5'-terminal cap of mRNA in presence of EIF-4F and ATP. Promotes the ATPase activity and the ATP-dependent RNA unwinding activity of both EIF4-A and EIF4-F (By similarity).|||Self-associates and interacts with EIF3 p170 subunit. http://togogenome.org/gene/10090:Mlycd ^@ http://purl.uniprot.org/uniprot/Q99J39 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-471 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-471 by SIRT4 represses activity, leading to promote lipogenesis.|||Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. Plays a role in controlling the extent of ischemic injury by promoting glucose oxidation.|||Cytoplasm|||Homotetramer. Dimer of dimers. The two subunits within a dimer display conformational differences suggesting that at any given moment, only one of the two subunits is competent for malonyl-CoA binding and catalytic activity. Under oxidizing conditions, can form disulfide-linked homotetramers (in vitro). Associates with the peroxisomal targeting signal receptor PEX5 (By similarity).|||Interchain disulfide bonds may form in peroxisomes (Potential). Interchain disulfide bonds are not expected to form in the reducing environment of the cytoplasm and mitochondria.|||Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions.|||May be produced by alternative initiation at Met-39 of isoform mitochondrial. Alternatively, represents a proteolytic processed form of the mitochondrial form.|||Mice show an increased expression of genes regulating fatty acid utilization and likely contributes to the absence of changes in energy metabolism in the aerobic heart. Display a preference for glucose utilization after ischemia and improve functional recovery of the heart.|||Mitochondrion matrix|||Peroxisome|||Peroxisome matrix http://togogenome.org/gene/10090:Tmc4 ^@ http://purl.uniprot.org/uniprot/F8VQ45|||http://purl.uniprot.org/uniprot/Q7TQ65 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMC family.|||Membrane|||Probable ion channel.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Crabp2 ^@ http://purl.uniprot.org/uniprot/P22935 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||By retinoic acid.|||Cytoplasm|||Embryo and skin of adult mouse.|||Endoplasmic reticulum|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Interacts with importin alpha (By similarity). Interacts with RXR and RARA.|||Nucleus|||Sumoylated in response to retinoic acid binding, sumoylation is critical for dissociation from ER and subsequent nuclear translocation.|||Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors. http://togogenome.org/gene/10090:Lipn ^@ http://purl.uniprot.org/uniprot/Q3U4B4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Plays a highly specific role in the last step of keratinocyte differentiation. May have an essential function in lipid metabolism of the most differentiated epidermal layers (By similarity).|||Secreted http://togogenome.org/gene/10090:Clmp ^@ http://purl.uniprot.org/uniprot/Q8R373 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||May be involved in the cell-cell adhesion. May play a role in adipocyte differentiation and development of obesity. Is required for normal small intestine development (By similarity).|||Predominantly expressed in epithelial cells within different tissues and in the white adipose tissue. Expressed at high levels in the heart and brain, at intermediate levels in the lung, skeletal muscle, kidney and testis and at low levels in the liver and spleen.|||Up-regulated in mature adipocytes and adipocyte tissue of obese animals.|||tight junction http://togogenome.org/gene/10090:Or52a24 ^@ http://purl.uniprot.org/uniprot/K7N6B2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5ak25 ^@ http://purl.uniprot.org/uniprot/Q8VF74 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prps2 ^@ http://purl.uniprot.org/uniprot/Q9CS42 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Activated by magnesium and inorganic phosphate. Competitively or non-competitively inhibited by ADP, 2,3-bisphosphoglyceride or GDP (By similarity).|||Belongs to the ribose-phosphate pyrophosphokinase family.|||Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.|||Homodimer. The active form is probably a hexamer composed of 3 homodimers (By similarity). http://togogenome.org/gene/10090:Tmem198b ^@ http://purl.uniprot.org/uniprot/Q8CFU0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM198 family.|||Membrane http://togogenome.org/gene/10090:Cfap73 ^@ http://purl.uniprot.org/uniprot/J3QPZ5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CFAP73 family.|||May play a role in ciliary/flagellar motility by regulating the assembly and the activity of axonemal inner dynein arm.|||cilium axoneme http://togogenome.org/gene/10090:Tmem106c ^@ http://purl.uniprot.org/uniprot/Q80VP8 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM106 family.|||Endoplasmic reticulum membrane|||Interacts with TMEM106B.|||Membrane http://togogenome.org/gene/10090:Ccdc30 ^@ http://purl.uniprot.org/uniprot/Q8BVF4 ^@ Similarity ^@ Belongs to the prefoldin subunit beta family. http://togogenome.org/gene/10090:Or10x4 ^@ http://purl.uniprot.org/uniprot/A2RS36|||http://purl.uniprot.org/uniprot/E9Q1L6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Selp ^@ http://purl.uniprot.org/uniprot/Q01102 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the selectin/LECAM family.|||By TNF-alpha. Induced expression in lung, liver, kidney and heart after endotoxin treatment.|||Ca(2+)-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes. The ligand recognized is sialyl-Lewis X. Mediates rapid rolling of leukocyte rolling over vascular surfaces during the initial steps in inflammation through interaction with SELPLG.|||Cell membrane|||Interacts with SNX17. Interacts with SELPLG/PSGL1 and PODXL2 and mediates neutrophil adhesion and leukocyte rolling. This interaction requires the sialyl-Lewis X epitope of SELPLG and PODXL2, and specific tyrosine sulfation on SELPLG.|||Stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells. Upon cell activation by agonists, P-selectin is transported rapidly to the cell surface. http://togogenome.org/gene/10090:Med21 ^@ http://purl.uniprot.org/uniprot/Q9CQ39 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mediator complex subunit 21 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with THRA in a ligand-dependent fashion (By similarity). Interacts with PPARG.|||Expressed in brain, heart, kidney, liver, lung, skeletal muscles, spleen and testis.|||Nucleus http://togogenome.org/gene/10090:Vps37a ^@ http://purl.uniprot.org/uniprot/Q8CHS8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS37 family.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101, VPS28 and HGS. Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation (By similarity).|||Late endosome membrane|||Nucleus http://togogenome.org/gene/10090:Snx19 ^@ http://purl.uniprot.org/uniprot/Q6P4T1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Interacts with PTPRN.|||Plays a role in intracellular vesicle trafficking and exocytosis (PubMed:24843546). May play a role in maintaining insulin-containing dense core vesicles in pancreatic beta-cells and in preventing their degradation. May play a role in insulin secretion (PubMed:24843546). Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) (PubMed:25148684).|||The PX domain mediates specific binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)). http://togogenome.org/gene/10090:Elmo3 ^@ http://purl.uniprot.org/uniprot/A0A1D5RMK9|||http://purl.uniprot.org/uniprot/Q8BYZ7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1 (By similarity).|||Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1.|||Probably interacts directly with the SH3-domain of DOCK1 via its SH3-binding site. Part of a complex with DOCK1 and RAC1 (By similarity). Interacts with ADGRB3 (By similarity). http://togogenome.org/gene/10090:Rnf148 ^@ http://purl.uniprot.org/uniprot/G3X9R7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Olfr209 ^@ http://purl.uniprot.org/uniprot/L7N1X3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nutf2 ^@ http://purl.uniprot.org/uniprot/P61971 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Interacts with RAN (GDP-bound form); the interaction is direct and regulates RAN nuclear import. Interacts with the nucleoporins NUP54, NUP58 and NUP62 (via FG repeats); recruits NUTF2 to the nuclear pore complex a step required for NUTF2-mediated GDP-bound RAN nuclear import. Interacts with CAPG; mediates its nuclear import.|||Mediates the import of GDP-bound RAN from the cytoplasm into the nucleus which is essential for the function of RAN in cargo receptor-mediated nucleocytoplasmic transport. Thereby, plays indirectly a more general role in cargo receptor-mediated nucleocytoplasmic transport. Interacts with GDP-bound RAN in the cytosol, recruits it to the nuclear pore complex via its interaction with nucleoporins and promotes its nuclear import.|||Nucleus inner membrane|||Nucleus outer membrane|||cytosol|||nuclear pore complex|||nucleoplasm http://togogenome.org/gene/10090:Adamtsl4 ^@ http://purl.uniprot.org/uniprot/Q80T21 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although similar to members of the ADAMTS family, it lacks the metalloprotease and disintegrin-like domains which are typical of that family.|||Glycosylated (By similarity). Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Interacts with CTSB. Interacts with FBN1 (By similarity).|||Positive regulation of apoptosis. May facilitate FBN1 microfibril biogenesis (By similarity).|||Widely expressed in a range of tissues. Especially prevalent in brain, spinal cord, muscle, lung and heart.|||extracellular matrix http://togogenome.org/gene/10090:Cyp11b2 ^@ http://purl.uniprot.org/uniprot/G3UWE4|||http://purl.uniprot.org/uniprot/P15539 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure. Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone (21-hydroxyprogesterone), namely 11-beta hydroxylation, followed by two successive oxidations at C18 yielding 18-hydroxy and then 18-oxo intermediates (that would not leave the enzyme active site during the consecutive hydroxylation reactions), ending with the formation of aldosterone. Can also produce 18-hydroxycortisol and 18-oxocortisol, derived from successive oxidations of cortisol at C18, normally found at very low levels, but significantly increased in primary aldosteronism, the most common form of secondary hypertension. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin). Could also be involved in the androgen metabolic pathway.|||Belongs to the cytochrome P450 family.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nipbl ^@ http://purl.uniprot.org/uniprot/Q6KCD5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCC2/Nipped-B family.|||Chromosome|||Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.|||Deletion of NIPBL in mouse liver leads to strong depletion of chromatin-bound cohesin and marked reorganization of chromosomal folding. Cells retain transcriptionally active (type A) and transcriptionally inactive (type B) compartments, but lose topologically associating domains (TADs) patterns and TAD-associated peaks of contact enrichment across the whole genome. The compartmentalization of chromatin in cells lacking NIPBL is enhanced around 1.8-fold compared with controls.|||Heterodimerizes with MAU2/SCC4 to form the cohesin loading complex (By similarity). The NIPBL-MAU2 heterodimer interacts with the cohesin complex composed of SMC1A/B and SMC3 heterodimer, RAD21 and STAG1/SA1. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (By similarity). Interacts directly (via PxVxL motif) with CBX3 and CBX5 (By similarity). Interacts with ZNF609 (via N-terminus) (PubMed:28041881). Interacts with the multiprotein complex Integrator (PubMed:28041881).|||Nucleus|||Plays an important role in the loading of the cohesin complex on to DNA (PubMed:29094699). Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin. Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (By similarity). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (PubMed:28041881).|||Spermatocytes and oocytes (at protein level).|||The C-terminal region containing HEAT repeats and Pro-Xaa-Val-Xaa-Leu (PxVxL) motif are involved in the recruitment of NIPBL to sites of DNA damage.|||Widely expressed at 9.5 and 10.5 dpc, with notable accumulations in limb bud, branchial arch and craniofacial mesenchyme. These regions are involved in patterning of the skeleton and soft tissues of the limbs, jaw and face. Expressed in the developing brain, with enrichment in the ventricular zone at 14.5 dpc (PubMed:28041881). http://togogenome.org/gene/10090:Kcnd2 ^@ http://purl.uniprot.org/uniprot/Q9Z0V2 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.|||Cell junction|||Cell membrane|||Detected in hippocampus, thalamus, medial habenular nucleus, striatum, amygdala, brain cortex and cerebellum (PubMed:11040264, PubMed:17122039, PubMed:18187474, PubMed:20371829, PubMed:22612819). Detected in hippocampus CA1 and CA3 layer, in stratum oriens, stratum radiatum and stratum lacunosum-moleculare and in dentate gyrus (PubMed:16009497, PubMed:22098631). Detected in dorsal horn neurons; colocalizes with GRM5 (PubMed:18045912). C-terminally phosphorylated forms are detected in the stratum radiatum and in basilar dendrites in stratum oriens in hippocampus CA1 and on cell bodies in hippocampus CA3 layers, with lower levels in stratum lacunosum-moleculare (PubMed:11040264). In contrast, N-terminally phosphorylated forms are detected in stratum lacunosum moleculare in the hippocampus CA1 layer (PubMed:11040264). Both C-terminally and N-terminally phosphorylated forms are observed on cell bodies and neuronal processes in the amygdala (PubMed:11040264). C-terminally phosphorylated forms are detected in the dentate gyrus molecular layer, while N-terminally phosphorylated forms are detected in the hilus of the dentate gyrus (PubMed:11040264). Both N-terminally and C-terminally phosphorylated forms are detected in the somatosensory cortex (PubMed:11040264). C-terminally phosphorylated forms are detected in the cerebellum granular layers (PubMed:11040264). Detected in heart ventricle myocytes (at protein level) (PubMed:9734479, PubMed:11909823, PubMed:16293790, PubMed:23713033). Detected in brain and heart (PubMed:16293790).|||Homotetramer or heterotetramer with KCND3 or KCND1 (PubMed:9734479, PubMed:11909823, PubMed:19713751, PubMed:20943905). Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905). In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Interacts with DLG1 (By similarity). Interacts with DLG4 (By similarity). Interacts with NCS1/FREQ (PubMed:11606724). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity). Interacts with FLNA and FLNC (By similarity). Interacts with DPP6 and DPP10 (PubMed:19713751, PubMed:22311982). Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity).|||Is specifically and reversibly inhibited by the scorpion toxin Ts8 (AC P69940).|||Mice are viable, fertile and appear to be in good health (PubMed:16293790, PubMed:22738428). The loss of KCND2 has only minor functional consequences, probably due to an increase of the activity of other potassium channels, even though there is no visible change of their expression levels (PubMed:20371829). Mutant mice show no sign of heart dysfunction, but the fast component of the rapidly inactivating and rapidly recovering potassium current I(to) is lost in their ventricular myocytes (PubMed:16293790). Instead, a slowly inactivating current is expressed that is not observed in wild-type (PubMed:16293790). Electrocardiograms of mutant hearts display no significant differences relative to wild-type regarding their QT, PR, QRS and RR intervals (PubMed:16293790). The neuronal A-type current is reduced by about 80% in brain cortex and hippocampus CA1 pyramidal neurons, by about 50% in suprachiasmatic nucleus neurons and by about 60% in dorsal horn neurons (PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518). The dendritic A-type current is abolished in pyramidal neurons from the hippocampus CA1 layer (PubMed:17122039). Concomitantly, the back-propagation of action potential in dendrites is increased (PubMed:17122039). This may lower the treshold for neuronal long-term potentiation (LTP) (PubMed:17122039). Loss of KCND2 does not influence the levels of KCND3 or KCNA4, but leads to reduced KCNIP1, KCNIP2 and KCNIP3 protein levels (PubMed:17122039, PubMed:18187474, PubMed:22612819). Mutant mice show only minor differences in their behavior when compared to wild-type; they display hyperactivity to some, but not all, novel stimuli (PubMed:22738428). Mutant mice show subtle spatial learning deficits (PubMed:20857488). Mutant mice display shorter periods of locomotor activity that wild-type littermates, due to a corresponding change in the circadian rhythm of repetitive firing in suprachiasmatic nucleus neurons (PubMed:22815518). Mutant mice display loss of spontaneous nociceptive behavior that is caused by the activation of GRM5 (PubMed:18045912).|||Perikaryon|||Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites. Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3. Phosphorylation at Ser-552 leads to KCND2 internalization (By similarity). Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5 (PubMed:18045912). Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (PubMed:18045912).|||Postsynaptic cell membrane|||Synapse|||The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation. It is required for interaction with KCNIP2, and probably other family members as well.|||The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (By similarity). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By similarity). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation.|||The transient neuronal A-type potassium current called I(SA) is triggered at membrane potentials that are below the threshold for action potentials. It inactivates rapidly and recovers rapidly from inactivation. It regulates the firing of action potentials and plays a role in synaptic integration and plasticity. Potassium channels containing KCND2 account for about 80% of the neuronal A-type potassium current. In contrast, the potassium channel responsible for the cardiac I(to) current differs between species; it is mediated by KCND2 in rodents. In human and other non-rodents KCND3 may play an equivalent role.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (PubMed:10818150, PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites (PubMed:10818150, PubMed:17122039, PubMed:22815518). Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (PubMed:22815518). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (PubMed:18045912). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member (PubMed:9734479, PubMed:10601491, PubMed:11909823, PubMed:23713033). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:9734479, PubMed:22311982). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel (PubMed:11909823). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:11909823). Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (By similarity). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:22311982).|||caveola|||dendrite|||dendritic spine|||sarcolemma http://togogenome.org/gene/10090:Slc1a1 ^@ http://purl.uniprot.org/uniprot/P51906 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A1 subfamily.|||Cell membrane|||Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.|||Detected on neurons in the brain cortex, dentate gyrus and hippocampus CA2 region (at protein level) (PubMed:30840898). Expressed in whole brain, brain cortex, hippocampus, cerebellum, lung, kidney, small intestine and skeletal muscle (PubMed:30840898, PubMed:7766664, PubMed:9233792). Expressed in the renal outer medulla, medullary ray and cortex (at protein level) (PubMed:26739563).|||Early endosome membrane|||Homotrimer (Probable). Interacts with ARL6IP5 (PubMed:12119102, PubMed:18684713). Interacts with RTN2 (via N-terminus); the interaction promotes cell surface expression of SLC1A1 (By similarity). Interacts with SORCS2; this interaction is important for normal expression at the cell membrane (PubMed:30840898).|||Late endosome membrane|||No visible phenotype at birth. Mice are born at the expected Mendelian rate, are viable and fertile, and do not develop any neurological symptoms with increasing age. They show decreased spontaneous locomotor activity. Besides, urinary excretion of glutamate and aspartate are strongly increased, but glutamate and aspartate serum levels are normal.|||Recycling endosome membrane|||Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:12119102, PubMed:18684713). Can also transport L-cysteine (PubMed:30840898). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (By similarity). Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (PubMed:9233792). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (PubMed:9233792). Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport (PubMed:30840898). Negatively regulated by ARL6IP5 (PubMed:12119102).|||synaptosome http://togogenome.org/gene/10090:Serpinb3a ^@ http://purl.uniprot.org/uniprot/G3X9V8|||http://purl.uniprot.org/uniprot/Q8BG86 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Lmod3 ^@ http://purl.uniprot.org/uniprot/E9QA62 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A band|||Belongs to the tropomodulin family.|||Cytoplasm|||Essential for the organization of sarcomeric actin thin filaments in skeletal muscle (PubMed:25774500, PubMed:26035871). Increases the rate of actin polymerization (By similarity).|||Expressed by 15.5 dpc in both skeletal muscle and heart. Expression is maintained throughout adulthood.|||Expression is regulated by SRF and MEF2.|||M line|||May interact with tropomyosin alpha (TPM1/2) N-terminus (By similarity). Interacts with KLHL40; leading to stabilization (PubMed:24960163).|||Mice show severe muscle weakness and postnatal growth retardation. Skeletal muscles show the presence of nemaline bodies and have disorganized sarcomeric structures. Muscle atrophy is specific to the fast fibers.|||Skeletal muscle and heart-specific (at protein level).|||Ubiquitinated, leading to its degradation. Interaction with KLHL40 negatively regulates ubiquitination and degradation.|||cytoskeleton http://togogenome.org/gene/10090:Cp ^@ http://purl.uniprot.org/uniprot/G3X8Q5|||http://purl.uniprot.org/uniprot/Q61147 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the multicopper oxidase family.|||Binds 6 Cu cations per monomer.|||Ceruloplasmin is a blue, copper-binding (6-7 atoms per molecule) glycoprotein. It has ferroxidase activity oxidizing Fe(2+) to Fe(3+) without releasing radical oxygen species. It is involved in iron transport across the cell membrane. Provides Cu(2+) ions for the ascorbate-mediated deaminase degradation of the heparan sulfate chains of GPC1. May also play a role in fetal lung development or pulmonary antioxidant defense (By similarity).|||Expressed in many tissues, including liver, eye and brain.|||Secreted http://togogenome.org/gene/10090:Cldn19 ^@ http://purl.uniprot.org/uniprot/Q3UNX6|||http://purl.uniprot.org/uniprot/Q9ET38 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts (via both extracellular domains) with Clostridium perfringens enterotoxin CPE; the interaction disrupts claudin assembly in tight junctions.|||Belongs to the claudin family.|||Cell membrane|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Serpini1 ^@ http://purl.uniprot.org/uniprot/O35684 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Detected in neurons in embryonic brain cortex (at protein level) (PubMed:17040209). During embryonic development mostly expressed in CNS (PubMed:9364046). In adult expressed in brain and much less in spinal cord, heart, kidney and testis (PubMed:9364046).|||Perikaryon|||Secreted|||Serine protease inhibitor that inhibits plasminogen activators and plasmin but not thrombin (PubMed:9364046, PubMed:11557034). May be involved in the formation or reorganization of synaptic connections as well as for synaptic plasticity in the adult nervous system. May protect neurons from cell damage by tissue-type plasminogen activator (Probable).|||secretory vesicle lumen http://togogenome.org/gene/10090:Rere ^@ http://purl.uniprot.org/uniprot/Q80TZ9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ At 8.25 dpc expression is strongly elevated in the anterior midline. At 8.5 dpc expression is elevated throughout the anteroposterior extent of the notochord and is down-regulated in the heart. At 8.75 dpc expression is increased in the ventral brain. At 9.5 dpc strong expression appears besides the notochord including the apical ectodermal ridge (AER), the isthmus and the ventral diencephalon. At 10.5 dpc expression increases in the notochord, the AER and spinal and brain neurons.|||Interacts with HDAC1 and ATN1. Interaction with ATN1 is improved when the poly-Gln region of ATN1 is extended. Interacts with FAT1 (By similarity).|||Mice embryos exhibit a variety of patterning defects that first appear at 8.0 dpc. Defects include a specific failure in ventralization of the anterior neural plate, loss of heart looping and irregular partitioning of somites. In mutant embryos, Shh expression fails to initiate along the anterior midline at 8.0 dpc, and Fgf8 is delocalized from the anterior neural ridge at 8.5 dpc.|||PML body|||Plays a role as a transcriptional repressor during development. May play a role in the control of cell survival.|||The interaction with ATN1 is mediated by the coiled domain. http://togogenome.org/gene/10090:Ccdc38 ^@ http://purl.uniprot.org/uniprot/Q8CDN8 ^@ Subcellular Location Annotation ^@ centrosome http://togogenome.org/gene/10090:Rhoc ^@ http://purl.uniprot.org/uniprot/Q62159 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Cleavage furrow|||Interacts with RTKN (PubMed:8662891). Interacts with AKAP13. Interacts with DIAPH1 (By similarity). Interacts with PKN2 (PubMed:20974804). Interacts with ROCK1 and ROCK2. Interacts with ARHGDIA. Interacts with RIPOR1 (By similarity).|||Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells.|||Up-regulated in silica-treated macrophages. http://togogenome.org/gene/10090:Map7d2 ^@ http://purl.uniprot.org/uniprot/A2AG50|||http://purl.uniprot.org/uniprot/Q3TS73 ^@ Similarity ^@ Belongs to the MAP7 family. http://togogenome.org/gene/10090:Eif6 ^@ http://purl.uniprot.org/uniprot/O55135|||http://purl.uniprot.org/uniprot/Q545K4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eIF-6 family.|||Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity. In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR (PubMed:26383020). Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (PubMed:26391622). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (By similarity). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (PubMed:21665150).|||Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity. In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis. Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC. Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth.|||Cytoplasm|||Detected in bladder, duodenum, liver, esophagus, pancreas, adipose tissue, megakaryocytes and testis with lower levels in muscle (at protein level).|||Embryonic lethality. Embryos die at preimplantation stage.|||Monomer. Associates with the 60S ribosomal subunit. Interacts with RACK1. Interacts with DICER1, AGO2, TARBP2, MOV10 and RPL7A; they form a large RNA-induced silencing complex (RISC).|||Phosphorylation at Ser-174 and Ser-175 by CSNK1D/CK1 promotes nuclear export.|||Phosphorylation at Ser-174 and Ser-175 promotes nuclear export.|||Ufmylated by UFL1.|||nucleolus http://togogenome.org/gene/10090:Tmem74 ^@ http://purl.uniprot.org/uniprot/Q8BQU7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM74 family.|||Lysosome membrane|||Plays an essential role in autophagy. TMEM74-induced autophagy may involve PI3K signal transduction (By similarity).|||autophagosome membrane http://togogenome.org/gene/10090:Otogl ^@ http://purl.uniprot.org/uniprot/F7A4A7 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ At 17.5 dpc, primarily detected in the spiral prominence and the Claudius cells and weakly in hair cells (at protein level). Also detected in the lumen surface of interdental cells in the proximity of Reissner's membrane and at the base of nascent tectorial membrane (at protein level). Similar expression pattern in P0 cochlea, with additional detection in some supporting cells (at protein level). At the same stage, in saccule, weakly expressed in hair cells and more prominently in the saccular roof (at protein level). By P6, expression becomes more restricted. Mainly detected in the outer hair cells, Deiter's cells and Claudius cells (at protein level). In the tectorial membrane, localized to the base. In the saccule, detected at high levels in the saccule roof with little change in the hair cells (at protein level).|||Belongs to the otogelin family.|||Secreted http://togogenome.org/gene/10090:Ifna9 ^@ http://purl.uniprot.org/uniprot/A0A7R8C3E4|||http://purl.uniprot.org/uniprot/P09235 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.|||Secreted http://togogenome.org/gene/10090:Pnpla3 ^@ http://purl.uniprot.org/uniprot/Q91WW7 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Lipid droplet|||Membrane|||Restricted to adipose tissue. Expressed in inguinal and epididymal white adipose tissues and in interscapular brown adipose tissue (PubMed:11431482). Also expressed in liver in response to high-sucrose diet (PubMed:22560221).|||Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. Does not esterify other lysophospholipids. Acyl donors are long chain (at least C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally possesses low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities and thus may play a role in acyl-chain remodeling of triglycerides (By similarity). In vitro may express hydrolytic activity against glycerolipids triacylglycerol, diacylglycerol and monoacylglycerol, with a strong preference for oleic acid as the acyl moiety (By similarity). However, the triacylglycerol hydrolase activity is controversial and may be very low (PubMed:22560221). Possesses phospholipase A2 activity (By similarity).|||Up-regulated in response to high-sucrose diet. http://togogenome.org/gene/10090:Skp2 ^@ http://purl.uniprot.org/uniprot/Q9Z0Z3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3 (By similarity).|||Cytoplasm|||Nucleus|||Part of a SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and SKP2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with ASB2 which is the substrate-recognition component of a probable ECS E3 ubiquitin-protein ligase complex; ASB2 is likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex. Interacts with CKS1. Interacts with the cyclin-A-CDK2 complex. Interacts with ORC1, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1, UBP43, MYC, TOB1, TAL1 and KMT2A/MLL1. Interacts with TRIM21 (By similarity). Interacts with cyclin-E (PubMed:10790373). Interacts with CARM1 (PubMed:30366907).|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (By similarity). Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (PubMed:10790373). Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (By similarity).|||Through the ubiquitin-mediated proteasomal degradation of viral proteins may have an antiviral activity.|||Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13 (By similarity). http://togogenome.org/gene/10090:Map1b ^@ http://purl.uniprot.org/uniprot/P14873 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3 different light chains, LC1, LC2 and LC3, can associate with MAP1A and MAP1B proteins. LC1 interacts with the amino-terminal region of MAP1B. Interacts with ANP32A and TIAM2 (PubMed:12807913, PubMed:17320046). Interacts with the tubulin tyrosine TTL (PubMed:18075266). Interacts (via C-terminus) with GAN (via Kelch domains) (PubMed:12147674). Interacts (via N-terminus) with DAPK1 (By similarity). Interacts with TMEM185A (By similarity). Interacts with MAP1LC3B (By similarity). Interacts with KIRREL3 (By similarity). MAP1 light chain LC1 (via C-terminus): Interacts with ELAVL4; the interaction contributes to the association of ELAVL4 with microtubules (PubMed:21288476). MAP1 light chain LC1: Interacts with ELAVL2 and ELAVL3 (PubMed:21288476).|||Belongs to the MAP1 family.|||Cytoplasm|||Has a highly basic region with many copies of the sequence KKEE and KKEI/V, repeated but not at fixed intervals, which is responsible for the binding of MAP1B to microtubules.|||Highly expressed in brain and cochlea, mildly expressed in heart, and very weakly expressed in liver and muscle. In the cochlea, it is abundantly expressed in spiral ganglions.|||LC1 is coexpressed with MAP1B. It is a polypeptide generated from MAP1B by proteolytic processing. It is free to associate with both MAP1A and MAP1B. It interacts with the N-terminal region of MAP1B.|||Required for proper microtubule dynamics. Plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing (By similarity). Facilitates tyrosination of alpha-tubulin in neuronal microtubules. Required for synaptic maturation.|||S-nitrosylation at Cys-2460 enhances interaction with microtubules, and may act as an effector modification for neuronal nitric oxide synthase control of growth-cone size, growth-cone collapse and axon retraction.|||Synapse|||cytoskeleton|||dendritic spine http://togogenome.org/gene/10090:Ryr1 ^@ http://purl.uniprot.org/uniprot/E9PZQ0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by reversible S-nitrosylation (PubMed:22036948). Repeated very high-level exercise increases S-nitrosylation.|||Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1 subfamily.|||Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2844 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2844.|||Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:18003898, PubMed:7515481, PubMed:7621815, PubMed:21156754). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain (PubMed:22036948). Required for normal embryonic development of muscle fibers and skeletal muscle (PubMed:7515481). Required for normal heart morphogenesis, skin development and ossification during embryogenesis (PubMed:18003898, PubMed:7515481).|||Detected in muscle and myotubes (at protein level) (PubMed:18003898). Ubiquitous. Detected in diaphragm, skeletal muscle, esophagus, spleen, submaxillary gland, adrenal gland, cerebellum, brain and in testis germ cells.|||Homotetramer (PubMed:18003898). Can also form heterotetramers with RYR2 (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1) (PubMed:18268335). Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity (By similarity). Interacts with S100A1 (By similarity). Interacts with FKBP1A; this stabilizes the closed conformation of the channel. Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity. Interacts with SELENON (By similarity). Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (By similarity).|||Perinatal lethality, due to severe defects in skeletal muscle development. Neonates do not breathe and do not move. Mutant mice show defects in muscle fiber development. Their muscles do not show a contractile response to electrical stimulation. In addition, mice display abnormal curvature of the spine, thin limbs, and an abnormal rib cage.|||Sarcoplasmic reticulum membrane|||The calcium release channel activity resides in the C-terminal region while the remaining part of the protein constitutes the 'foot' structure spanning the junctional gap between the sarcoplasmic reticulum (SR) and the T-tubule (PubMed:7621815, PubMed:7724570). Pore opening is mediated via the cytoplasmic calcium-binding domains that mediate a small rotation of the channel-forming transmembrane regions that then leads to channel opening (By similarity).|||The calcium release is activated by increased cytosolic calcium levels, by nitric oxyde (NO), caffeine and ATP (PubMed:7621815, PubMed:22036948, PubMed:21156754). Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity (PubMed:7621815). Channel activity is regulated by calmodulin (CALM). Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites. http://togogenome.org/gene/10090:Snrk ^@ http://purl.uniprot.org/uniprot/Q8VDU5 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by phosphorylation on Thr-173.|||Autophosphorylated. Phosphorylation on Thr-173 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Expressed from day 8 dpc along the epithelium of the differentiating neural tube. Expression persists along the dorsal axis until 12.5 dpc, but becomes progressively restricted to the more caudal part of the neural tube with much stronger intensity in the caudal neuropore. Also observed in the endoderm of the primitive gut between 8.5 and 11.5 dpc, at 10.5 dpc, in the endocardium and pericardium of the developing heart, and in both the endothelium and blood cells clustered at the ventral part of the dorsal aorta. Later in development (12.5 dpc), expressed in the endocardium and the interventricular septum of the heart.|||May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis (By similarity).|||Nucleus|||Ubiquitously expressed in all tissues examined. http://togogenome.org/gene/10090:Vmn1r230 ^@ http://purl.uniprot.org/uniprot/Q8R2A2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Papln ^@ http://purl.uniprot.org/uniprot/Q9EPX2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the papilin family.|||Secreted http://togogenome.org/gene/10090:Or14c44 ^@ http://purl.uniprot.org/uniprot/Q7TS04 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Spag11a ^@ http://purl.uniprot.org/uniprot/Q0VB31|||http://purl.uniprot.org/uniprot/Q8K4N2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antimicrobial activity against E.coli (By similarity). Plays a role in the defense response in the male reproductive tract, contributing to sperm maturation, storage and protection (By similarity).|||Secreted http://togogenome.org/gene/10090:Mrgbp ^@ http://purl.uniprot.org/uniprot/Q9DAT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EAF7 family.|||Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.|||Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. MRGBP may interact directly with MORF4L1/MRG15 and MORF4L2/MRGX (By similarity).|||Nucleus http://togogenome.org/gene/10090:Nfkbiz ^@ http://purl.uniprot.org/uniprot/Q9EST8 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By IL-1, LPS, peptidoglycan, bacterial lipoprotein, flagellin, MALP-2, R-848 and CpG DNA, but not by TNF-alpha.|||Expressed in kidney, liver, lung and heart. Expressed at very low levels in skeletal muscle, spleen and brain.|||Interacts with NFKB1/p50 (PubMed:11356851). Interacts with RELA (By similarity). Interacts with AKIRIN2 (PubMed:25107474).|||Involved in regulation of NF-kappa-B transcription factor complexes (PubMed:11356851, PubMed:15241416, PubMed:15618216, PubMed:17447895). Inhibits NF-kappa-B activity without affecting its nuclear translocation upon stimulation (PubMed:11356851, PubMed:15241416, PubMed:15618216, PubMed:17447895). Inhibits DNA-binding of RELA and NFKB1/p50, and of the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer (PubMed:11356851, PubMed:15241416, PubMed:15618216, PubMed:17447895). Seems also to activate NF-kappa-B-mediated transcription (PubMed:11356851, PubMed:15241416, PubMed:15618216, PubMed:17447895). In vitro, upon association with NFKB1/p50 has transcriptional activation activity and, together with NFKB1/p50 and RELA, is recruited to LCN2 promoters (By similarity). Promotes transcription of LCN2 and DEFB4 (By similarity). Is recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha production in response to LPS (PubMed:11086164, PubMed:25107474). Seems to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling (PubMed:11086164, PubMed:25107474). Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR) (PubMed:25282160).|||Major.|||Mice have splenocytes with defective proliferation in response to LPS but not to anti-CD40, IL-4 and anti-IgM. Though mice grew normally after birth, some of them started to develop atopic dermatitis-like skin lesions with acanthosis and lichenoid changes at the age of 4-5 weeks. All mice developed the disease by the age of 10 weeks. 5-week-old mice show pathological changes in the conjunctiva, including a heavy lymphocyte infiltration into the submucosa and loss of goblet cells in the conjunctival epithelium.|||Nucleus http://togogenome.org/gene/10090:Zfp385b ^@ http://purl.uniprot.org/uniprot/Q8BXJ8 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with p53/TP53; the interaction is direct.|||Mainly expressed in developing brain.|||May play a role in p53/TP53-mediated apoptosis.|||Nucleus http://togogenome.org/gene/10090:Qtrt1 ^@ http://purl.uniprot.org/uniprot/Q9JMA2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the queuine tRNA-ribosyltransferase family.|||Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine) (PubMed:19414587, PubMed:29862811). Catalysis occurs through a double-displacement mechanism. The nucleophile active site attacks the C1' of nucleotide 34 to detach the guanine base from the RNA, forming a covalent enzyme-RNA intermediate. The proton acceptor active site deprotonates the incoming queuine, allowing a nucleophilic attack on the C1' of the ribose to form the product (By similarity).|||Cytoplasm|||Expressed in brain, heart, kidney, liver, ling, skeletal muscle, spleen and testis.|||Heterodimer of a catalytic subunit QTRT1 and an accessory subunit QTRT2.|||Mitochondrion outer membrane|||Nucleus http://togogenome.org/gene/10090:Gpd1l ^@ http://purl.uniprot.org/uniprot/B2RSR7|||http://purl.uniprot.org/uniprot/Q3ULJ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.|||Cytoplasm|||Interacts with SCN5A.|||Plays a role in regulating cardiac sodium current; decreased enzymatic activity with resulting increased levels of glycerol 3-phosphate activating the DPD1L-dependent SCN5A phosphorylation pathway, may ultimately lead to decreased sodium current; cardiac sodium current may also be reduced due to alterations of NAD(H) balance induced by DPD1L. http://togogenome.org/gene/10090:Tmigd3 ^@ http://purl.uniprot.org/uniprot/G3X8R9|||http://purl.uniprot.org/uniprot/Q497R5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. http://togogenome.org/gene/10090:Rps19bp1 ^@ http://purl.uniprot.org/uniprot/Q8C6B9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AROS family.|||Citrullinated by PADI4.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with RPS19; the interaction is direct and mediates the integration of RPS19 in state post-A1 (PubMed:16289379). Interacts with SIRT1 (By similarity).|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Acts as a chaperone that specifically mediates the integration of RPS19 in state post-A1. Direct regulator of SIRT1. Enhances SIRT1-mediated deacetylation of p53/TP53, thereby participating in inhibition of p53/TP53-mediated transcriptional activity.|||Widely expressed with higher levels in submaxillary gland and epididymis.|||nucleolus http://togogenome.org/gene/10090:Amd2 ^@ http://purl.uniprot.org/uniprot/D3Z6H8 ^@ Caution|||Cofactor|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the eukaryotic AdoMetDC family.|||Binds 1 pyruvoyl group covalently per subunit.|||Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.|||Heterotetramer of two alpha and two beta chains.|||Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The post-translation cleavage follows an unusual pathway, termed non-hydrolytic serinolysis, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl group blocking the N-terminus of the alpha chain.|||Product of an intronless, probably retrotransposed, copy of AMD1. mRNA levels are 10-40 times lower than AMD1 (PubMed:9620866). http://togogenome.org/gene/10090:Afap1 ^@ http://purl.uniprot.org/uniprot/Q80YS6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Can cross-link actin filaments into both network and bundle structures. May modulate changes in actin filament integrity and induce lamellipodia formation. May function as an adapter molecule that links other proteins, such as SRC and PKC to the actin cytoskeleton (By similarity).|||Monomer and homomultimer. Interacts via its C-terminus with F-actin; probably involving AFAP1 multimers. Interacts with activated SRC SH3-SH2 domains. Interacts via its PH 1 domain with PRKCA, PRKCB and PRKCI (By similarity).|||Phosphorylated on tyrosine residues by SRC.|||stress fiber http://togogenome.org/gene/10090:Ecm1 ^@ http://purl.uniprot.org/uniprot/Q61508 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the surrounding connective tissues of developing long bones, but not in the cartilage. The long isoform is expressed in a number of tissues including liver, heart and lungs. The short isoform is expressed in skin and cartilage-containing tissues such as tail and front paw. No expression is found in brain.|||Interacts (via C-terminus) with HSPG2 (via C-terminus). Interacts with EFEMP1/FBLN3 and LAMB3. Interacts with MMP9.|||Involved in endochondral bone formation as negative regulator of bone mineralization. Stimulates the proliferation of endothelial cells and promotes angiogenesis. Inhibits MMP9 proteolytic activity (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Brpf1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SUS4|||http://purl.uniprot.org/uniprot/A0A0N4SUT9|||http://purl.uniprot.org/uniprot/A0A0N4SVG7|||http://purl.uniprot.org/uniprot/B2RRD7|||http://purl.uniprot.org/uniprot/E9PXP1|||http://purl.uniprot.org/uniprot/Q3U109|||http://purl.uniprot.org/uniprot/Q80XK2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by KAT6A.|||Chromosome|||Component of some HBO1 complex composed of KAT7/HBO1, MEAF6, ING5, and BRPF1. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts (via PHD-type zinc finger domains) with unmethylated histone H3 at 'Lys-4' (H3K4me0). Interacts with trimethylated 'Lys-36' of histone H3 (H3K36me3). Interacts with ING5; interaction directs BRPF1 to H4K4me3-enriched chromatin at the 5' of active genes. Interacts with KAT7.|||Cytoplasm|||Embryonic lethality around embryonic day 9.5 caused by arrested vasculogenesis in the yolk sac and embryo proper (PubMed:24646517, PubMed:25773539). Embryos also display abnormal neural tube closure (PubMed:25773539).|||Expressed at low level in most tissues, with high expression in the testis and specific regions of the brain.|||Expressed in the placenta, yolk sac, limb buds, brain, spinal cord, retina, nose, bone and brown fat at the prenatal stages.|||Nucleus|||Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (By similarity). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac) (By similarity). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (By similarity). http://togogenome.org/gene/10090:Kmo ^@ http://purl.uniprot.org/uniprot/Q91WN4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the aromatic-ring hydroxylase family. KMO subfamily.|||Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract.|||Expressed by organs containing secondary lymphoid tissue, such as the lung, spleen, mesenteric lymph node, thymus and peripheral lymph nodes.|||Mitochondrion outer membrane|||Mutants show normal fecundity, fertility and longevity up tp 2 year. They have reduced serum 3-hydroxy-L-kynurenine concentrations. They are protected against extrapancreatic tissue injury to the lung, kidney and liver produced by acute pancreatitis-induced multiple organ dysfunction syndrome.|||Transmembrane domains are required for enzymatic activity. http://togogenome.org/gene/10090:Crtap ^@ http://purl.uniprot.org/uniprot/Q9CYD3 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the leprecan family.|||Defects in Crtap are a cause of osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production.|||Found in articular chondrocytes. Expressed in a variety of tissues.|||Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues.|||extracellular matrix http://togogenome.org/gene/10090:Eif5a ^@ http://purl.uniprot.org/uniprot/P63242 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by PCAF/KAT2B, regulating its subcellular localization (By similarity). Deacetylated by SIRT2 (By similarity).|||Belongs to the eIF-5A family.|||Binds to 80S ribosomes. Actively translating ribosomes show mutually exclusive binding of eIF5a (EIF5A or EIF5A2) and EEF2/eEF2 (By similarity). Interacts with DAPL1; interaction takes place at the polypeptide exit tunnel of hibernating ribosomes and prevents translation (By similarity). Interacts with DHPS. Interacts with SDCBP. Interacts with DOHH (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Lys-50 undergoes hypusination, a unique post-translational modification that consists in the addition of a butylamino group from spermidine to lysine side chain, leading to the formation of the unusual amino acid hypusine. eIF-5As are the only known proteins to undergo this modification, which is essential for their function.|||Nucleus|||Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts (By similarity). Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome (By similarity). Acts as ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step (By similarity). Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity (By similarity). With syntenin SDCBP, functions as a regulator of p53/TP53 and p53/TP53-dependent apoptosis (By similarity). Regulates also TNF-alpha-mediated apoptosis (By similarity). Mediates effects of polyamines on neuronal process extension and survival (PubMed:15377278). http://togogenome.org/gene/10090:Dpp6 ^@ http://purl.uniprot.org/uniprot/Q9Z218 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S9B family.|||Cell membrane|||Detected in brain cortex (at protein level).|||Homodimer (in vitro). Interacts with KCND2. Identified in a complex with KCND2 and KCNIP2. Forms an octameric complex composed of four DPP6 subunits bound to the KCND2 tetramer.|||Knockdown animals obtained using siRNA technology have smaller brains than their wild-type littermates. Performance on the standard Morris water maze indicated spatial memory defects and learning disabilities.|||N-glycosylated.|||Promotes cell surface expression of the potassium channel KCND2 (PubMed:22311982). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:22311982). Has no dipeptidyl aminopeptidase activity (By similarity). http://togogenome.org/gene/10090:H2-T23 ^@ http://purl.uniprot.org/uniprot/P06339|||http://purl.uniprot.org/uniprot/Q3V014 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin).|||Involved in the presentation of foreign antigens to the immune system.|||Membrane http://togogenome.org/gene/10090:Smim14 ^@ http://purl.uniprot.org/uniprot/Q91VT8 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Tlr3 ^@ http://purl.uniprot.org/uniprot/Q99MB1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Toll-like receptor family.|||Early endosome|||Endoplasmic reticulum membrane|||Endosome membrane|||Highly expressed in lung. After intraperitoneal injection of lipopolysaccharide, highly expressed in brain, heart, kidney, liver, lung and spleen.|||Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response (By similarity).|||Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes (PubMed:33432245). Interacts with SRC; upon binding of double-stranded RNA (By similarity). Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436).|||TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes (By similarity).|||Ubiquitinated by TRIM3; leading to recognition and sorting of polyubiquitinated TLR3 by the ESCRT complexes. Ubiquitinated by ZNRF1 via 'Lys-63'-linked ubiquitin chains; leading to TLR3 lysosomal trafficking and degradation.|||ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18. http://togogenome.org/gene/10090:Gtsf1 ^@ http://purl.uniprot.org/uniprot/Q9DAN6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UPF0224 (FAM112) family.|||Cytoplasm|||Expressed abundantly in adult testis, at moderate levels in unfertilized eggs and ovaries and weakly in embryonic stem cells.|||In the male gonad, barely detected at 13.5 dpc or at birth, detected weakly on postnatal day 14 and maximally expressed in the 4- or 7-week-old mouse testis but not detected in the epididymis of the 7-week-old mouse (at protein level). In the female gonad, low levels detected at birth (at protein level). In the adult testis, present predominantly in pachytene spermatocytes and round spermatids but not in spermatogonia, preleptotene spermatocytes or elongating spermatids (at protein level).|||Mutant mice grow normally and appear healthy but males are sterile due to massive germ cell apoptotic death after postnatal day 14 with meiocytes ceasing meiotic progression before the early meitoic phase. There is also increased transcription of LINE-1 and IAP retrotransposons accompanied by demethylation of their promoter regions.|||Required for spermatogenesis and is involved in the suppression of retrotransposon transcription in male germ cells. http://togogenome.org/gene/10090:Dgkh ^@ http://purl.uniprot.org/uniprot/A0A2I3BQ43|||http://purl.uniprot.org/uniprot/A0JP53|||http://purl.uniprot.org/uniprot/D3YXJ0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Cell membrane|||Cytoplasm|||Detected in ovary and uterus (at protein level).|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:27643686). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable). Plays a key role in promoting cell growth. Activates the Ras/B-Raf/C-Raf/MEK/ERK signaling pathway induced by EGF. Regulates the recruitment of RAF1 and BRAF from cytoplasm to membranes and their heterodimerization (By similarity).|||Does not form homooligomers.|||Homooligomers. Heterooligomers. Oligomerization through the SAM domain inhibits the diacylglycerol kinase activity. Heterooligomerizes with SAM domain-containing isoforms of DGKD.|||Interacts with RAF1 and BRAF.|||Phosphorylated. Phosphorylation does not inhibit catalytic activity.|||Specifically expressed in testis (PubMed:25613821, PubMed:27643686). Detected in the inner area of the testis (PubMed:25613821). Strongly expressed in the secondary spermatocytes and the round spermatids and weakly detected in the primary spermatocytes (PubMed:25613821).|||The SAM domain mediates homooligomerization.|||Widely expressed (PubMed:27643686). Detected in the granulosa cells of the primary and secondary follicles (PubMed:25613821). Expressed in mature follicles and corpus lutea (PubMed:25613821). Expressed in the oviductal epithelium (PubMed:25613821). In the uterus, strongly expressed in the luminal epithelium (PubMed:25613821). Detected in the uterine glands (PubMed:25613821).|||cytoskeleton http://togogenome.org/gene/10090:Asic1 ^@ http://purl.uniprot.org/uniprot/Q6NXK8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.|||Cell membrane|||Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix (By similarity).|||Expressed in brain areas receiving strong excitatory corticofugal input. In hippocampus, expressed in the hilus of the dentate gyrus. In the cerebral cortex expressed in anterior and posterior cingulate cortex, sensory and motor cortices. In the sensory cortex strongest expression is detected in the whisker barrel field. In sensorimotor and cingulate cortex expression is elevated in layer III. Also expressed in basal ganglia, striatum, ventral pallidum, olfactory tubercle, and nucleus accumbens. Weakly expressed in thalamus with the exception of the habenula and the medial septal nuclei. In olfactory bulb, preferentially expressed in the glomerular layer, within glomeruli. Expressed in cerebellum in the molecular and granule cell layers. Strongly expressed in amygdala complex, particularly in the lateral and basolateral nuclei. Isoform 1 is more abundant in brain compared to isoform 2 (at protein level). Expressed in the nodose ganglion and dorsal root ganglion. Expressed in dendritic spine cells.|||Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with PRKCABP and ASIC2 (By similarity). Interacts with STOM (PubMed:15471860).|||Inhibited by the diuretic amiloride.|||Mice display reduced spatial learning and memory capability, associated with absence of proton-gated currents in hippocampal neurons and impairment of hippocampal long term potentiation (LTP). They also show an increased mechanosensitivity of colonic and gastroesophageal mechanoreceptors and prolonged gastric emptying and an altered fear conditioning.|||Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel (By similarity).|||Potentiated by Ca(2+), Mg(2+), Ba(2+), multivalent cations and potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases. Inhibited by anti-inflammatory drugs like salicylic acid (By similarity).|||Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear. http://togogenome.org/gene/10090:Gja4 ^@ http://purl.uniprot.org/uniprot/P28235|||http://purl.uniprot.org/uniprot/Q3UPZ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family.|||Belongs to the connexin family. Alpha-type (group II) subfamily.|||Cell membrane|||Highly expressed in lung.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Trim50 ^@ http://purl.uniprot.org/uniprot/E9PVV5|||http://purl.uniprot.org/uniprot/Q810I2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by EP300 and KAT2B. HDAC6 drives TRIM50 deacetylation. Acetylation antagonizes with TRIM50 ubiquitination.|||Auto-ubiquitinated.|||Belongs to the TRIM/RBCC family.|||Can form dimers and trimers. Interacts with several E2 ubiquitin-conjugating enzymes, including UBE2L6, UBE2E1, UBE2E3. No interaction with UBE2H. Interacts with BECN1. Interacts with SQSTM1. Interacts with NLRP3 (PubMed:36178239).|||Cytoplasm|||E3 ubiquitin-protein ligase that ubiquitinates Beclin-1/BECN1 in a 'Lys-63'-dependent manner enhancing its binding to ULK1 (PubMed:29604308). In turn, promotes starvation-induced autophagy activation. Interacts also with p62/SQSTM1 protein and thereby induces the formation and the autophagy clearance of aggresome-associated polyubiquitinated proteins through HDAC6 interaction (PubMed:22792322). Promotes also NLRP3 inflammasome activation by directly inducing NLRP3 oligomerization independent of its E3 ligase function (PubMed:36178239).|||Expressed in the stomach.|||TRIM50-deficient mice show a significantly prolonged survival time when LPS-challenged when compared with wild-type mice. TRIM50 deficiency also significantly ameliorates NLRP3-mediated inflammation and tissue damage in vivo. http://togogenome.org/gene/10090:Vps35 ^@ http://purl.uniprot.org/uniprot/Q3TRJ1|||http://purl.uniprot.org/uniprot/Q9EQH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for endosomal localization of WASHC2 and mediates the association of the CSC with the WASH complex (By similarity).|||Belongs to the VPS35 family.|||Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS) formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35. The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (PubMed:21040701, PubMed:20875039, PubMed:21920005). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the affinity between the respective CSC and SNX-BAR subcomplexes is low. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (Probable). Interacts with VPS26A, VPS29, VPS26B and LRRK2 (PubMed:16190980, PubMed:21040701, PubMed:20875039, PubMed:21920005, PubMed:23395371). Interacts with SNX1, SNX2, IGF2R, SNX3, GOLPH3, SLC11A2, WASHC2, FKBP15, WASHC1, EHD1. Interacts with MAGEL2; leading to recruitment of the TRIM27:MAGEL2 E3 ubiquitin ligase complex retromer-containing endosomes (By similarity). Interacts with SORCS2 (PubMed:28469074).|||Cytoplasm|||Detected in striatum (at protein level) (PubMed:28469074). Ubiquitous. Highly expressed in fat tissue, testis, brain, kidney, thymus, liver and pancreas, and at lower levels in heart, intestine and skeletal muscle. Detected in oocytes, pre-implantation embryos and at 6.5-12.5 dpc.|||Early endosome|||Endosome|||Late endosome|||Membrane|||Plays a role in vesicular protein sorting. http://togogenome.org/gene/10090:Dhrs9 ^@ http://purl.uniprot.org/uniprot/Q148Q4|||http://purl.uniprot.org/uniprot/Q58NB6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3-alpha-hydroxysteroid dehydrogenase that converts 3-alpha-tetrahydroprogesterone (allopregnanolone) to dihydroxyprogesterone and 3-alpha-androstanediol to dihydroxyprogesterone. Also plays a role in the biosynthesis of retinoic acid. Can utilize both NADH and NADPH.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum membrane|||Homotetramer.|||Microsome membrane http://togogenome.org/gene/10090:Hectd3 ^@ http://purl.uniprot.org/uniprot/Q3U487 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin ligases accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of TRIOBP and its subsequent proteasomal degradation, thus facilitating cell cycle progression by regulating the turn-over of TRIOBP (By similarity). Mediates also ubiquitination of STX8.|||Interacts with TRIOBP (By similarity). Interacts with STX8.|||perinuclear region http://togogenome.org/gene/10090:Gmeb2 ^@ http://purl.uniprot.org/uniprot/P58929 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer, and heterodimer of GMEB1 and GMEB2. Interacts with the glucocorticoid receptor (NR3C1). May interact with CREB-binding protein (CBP) (By similarity).|||Nucleus|||Trans-acting factor that binds to glucocorticoid modulatory elements (GME) present in the TAT (tyrosine aminotransferase) promoter and increases sensitivity to low concentrations of glucocorticoids. Binds also to the transferrin receptor promoter (By similarity). http://togogenome.org/gene/10090:Rars2 ^@ http://purl.uniprot.org/uniprot/Q3U186 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Mitochondrion matrix http://togogenome.org/gene/10090:Hadhb ^@ http://purl.uniprot.org/uniprot/Q99JY0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-202 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the thiolase-like superfamily. Thiolase family.|||Endoplasmic reticulum|||Heterotetramer of 2 alpha/HADHA and 2 beta/HADHB subunits; forms the mitochondrial trifunctional enzyme (By similarity). Also purified as higher order heterooligomers including a 4 alpha/HADHA and 4 beta/HADHB heterooligomer which physiological significance remains unclear (By similarity). The mitochondrial trifunctional enzyme interacts with MTLN (PubMed:29949755). Interacts with RSAD2/viperin (By similarity).|||Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA. Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Amigo3 ^@ http://purl.uniprot.org/uniprot/Q8C2S7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. AMIGO family.|||Binds AMIGO1 or AMIGO2.|||May mediate heterophilic cell-cell interaction. May contribute to signal transduction through its intracellular domain (By similarity).|||Membrane|||Ubiquitous. http://togogenome.org/gene/10090:Atp5e ^@ http://purl.uniprot.org/uniprot/P56382|||http://purl.uniprot.org/uniprot/Q545F5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ATPase epsilon family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Prss46 ^@ http://purl.uniprot.org/uniprot/Q5M8S2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Membrane http://togogenome.org/gene/10090:Rasgef1b ^@ http://purl.uniprot.org/uniprot/Q8JZL7 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Constitutively expressed in brain, intestine and testis. Low constitutive expression, if any, in heart, lung, lymph nodes and thymus. Up-regulated in heart, kidney, liver, lymph nodes, spleen and thymus at day 20 after infection with Trypanosoma cruzi. Not detected in muscle.|||Early endosome|||Guanine nucleotide exchange factor (GEF) with specificity for RAP2A, it doesn't seems to activate other Ras family proteins (in vitro).|||In vitro, up-regulated in peritoneal macrophages by GPI-mucins, bacterial lipopolysaccharides (LPS) and poly(I:C). Small induction, if any, by IFNG alone. Induction is maximal 12 and 18 hours following LPS stimulation (at protein level). Also induced in T-helper cells activated by phytohemagglutinin. In vivo, up-regulated by infection with protozoan parasites, including Plasmodium chabaudi and Trypanosoma cruzi. This induction is dependent upon IFNG, MYD88 and TICAM1.|||Interacts with CCDC124 during cytokinesis (By similarity). Interacts with Ras family proteins.|||Late endosome|||Midbody http://togogenome.org/gene/10090:Gm21506 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Aqp1 ^@ http://purl.uniprot.org/uniprot/Q02013 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Detected in erythrocytes (at protein level) (PubMed:12133842). In the kidney, expressed on luminal and basal borders of proximal tubules and in the thin limb of Henle's loop (at protein level) (PubMed:31605441).|||Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (PubMed:12133842). Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (By similarity).|||Homotetramer. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1 (By similarity). Interacts with EPHB2; involved in endolymph production in the inner ear (PubMed:10839360). Identified in a complex with STOM. Interacts (via the N-terminal) with ANK1 (via ANK 1-5 repeats). Interacts (via the C-terminal) with EPB42 (By similarity).|||Mutant mice are born at the expected Mendelian rate and appear healthy and normal, but display strongly reduced urine osmolality. Besides, their erythrocytes show reduced water permeability. Mice lacking both Aqp1 and Slc14a1 are born at the expected Mendelian ratio, but do not thrive; half of them die within ten days after birth and none are alive after two weeks. Urine osmolality is somewhat lower than that observed with mice lacking only Aqp1. Besides, erythrocyte water permeability is significantly lower than in mice lacking only Aqp1.|||Pharmacologically inhibited by submillimolar concentrations of mercury. http://togogenome.org/gene/10090:Pld1 ^@ http://purl.uniprot.org/uniprot/D6RH77|||http://purl.uniprot.org/uniprot/Q6NVF2 ^@ Similarity ^@ Belongs to the phospholipase D family. http://togogenome.org/gene/10090:Mmadhc ^@ http://purl.uniprot.org/uniprot/Q99LS1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Heterodimer with MMACHC. Forms a multiprotein complex with MMACHC, MTR and MTRR.|||Involved in cobalamin metabolism and trafficking. Plays a role in regulating the biosynthesis and the proportion of two coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl). Promotes oxidation of cob(II)alamin bound to MMACHC. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine.|||Mitochondrion http://togogenome.org/gene/10090:Hao2 ^@ http://purl.uniprot.org/uniprot/Q9NYQ2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.|||Homotetramer.|||Oxidase that catalyzes the oxidation of medium chain hydroxyacids such as 2-hydroxyoctanoate, to the correspondong 2-oxoacids. Its role in the oxidation of 2-hydroxy fatty acids may contribute to the general pathway of fatty acid alpha-oxidation. Active in vitro with the artificial electron acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be the physiological electron acceptor, leading to the production of H2O2. Is not active on glycolate, glyoxylate, L-lactate, 2-hydroxybutanoate and 2-hydroxyhexadecanoate.|||Pancreas.|||Peroxisome|||Was originally thought to originate from human. http://togogenome.org/gene/10090:Ppp4c ^@ http://purl.uniprot.org/uniprot/P97470|||http://purl.uniprot.org/uniprot/Q3UNF2 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP phosphatase family.|||Belongs to the PPP phosphatase family. PP-4 (PP-X) subfamily.|||Binds 2 manganese ions per subunit.|||Cytoplasm|||Methylation at the C-terminal Leu-307 is critical for interactions with regulatory subunits and functions in DNA repair.|||Nucleus|||Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on Ser-140 (gamma-H2AX) generated during DNA replication and required for DNA double strand break repair (By similarity). Dephosphorylates NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1 activity in interphase. In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin (By similarity).|||Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complexes PPP4C-PPP4R1, PPP4C-PPP4R2, PPP4C-PPP4R2-PPP4R3A, PPP4C-PPP4R2-PPP4R3B and PPP4C-PPP4R4. The PPP4C-PPP4R2 complex appears to be a tetramer composed of 2 molecules of PPP4C and 2 molecules of PPP4R2. Interacts with REL, NFKB1/p50 and RELA. Interacts with SMN1 and GEMIN4. Interacts with IRS4 (phosphorylated). Interacts with SMEK1/PPP4R3A; the interaction requires PP4R2. Interacts with HDAC3 (By similarity).|||centrosome http://togogenome.org/gene/10090:Vmn1r215 ^@ http://purl.uniprot.org/uniprot/Q8R264 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mt2 ^@ http://purl.uniprot.org/uniprot/P02798 ^@ Domain|||Function|||Similarity ^@ Belongs to the metallothionein superfamily. Type 1 family.|||Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.|||Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids. http://togogenome.org/gene/10090:Arap1 ^@ http://purl.uniprot.org/uniprot/Q4LDD4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Golgi stack membrane|||Interacts with TNFRSF10A.|||Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Has a preference for ARF1 and ARF5 (By similarity). http://togogenome.org/gene/10090:Or5w20 ^@ http://purl.uniprot.org/uniprot/A2AVC0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dbn1 ^@ http://purl.uniprot.org/uniprot/Q9QXS6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (By similarity). Required for actin polymerization at immunological synapses (IS) and for the recruitment of the chemokine receptor CXCR4 to IS (By similarity). Plays a role in dendritic spine morphogenesis and organization, including the localization of the dopamine receptor DRD1 to the dendritic spines (PubMed:25865831). Involved in memory-related synaptic plasticity in the hippocampus (PubMed:25865831).|||Cell junction|||Cell projection|||Cytoplasm|||Expressed in the hippocampus, with expression in the pyramidal cells of CA1, CA2 and CA3 and in the granule cells of the dentate gyrus (at protein level) (PubMed:25865831). Highly expressed in brain, also present in stomach and to a lesser degree in kidney, colon, and urinary bladder (PubMed:10633083). The E2 isoform is specifically expressed in adult stomach, kidney, and cultured cells (PubMed:10633083).|||Interacts with RUFY3 (PubMed:24720729). Interacts with CXCR4; this interaction is enhanced by antigenic stimulation (By similarity). Interacts (via ADF-H domain) with ZMYND8 (via N-terminus); the interaction leads to sequestering of ZMYND8 in the cytoplasm (By similarity).|||Mice are born at the expected Mendelian frequency (PubMed:25865831). Mutant mice exhibit significant reduction of dendritic spine numbers, altered dendritic spine morphology with a reduction in the number of mushroom, thin and stubby types of dendritic spines, decreased protein levels of the neurotransmitter receptors DRD1, DRD2, HTR1A and 5HT7R and reduced numbers of DRD1 receptors on dendritic spines (PubMed:25865831). Inhibited memory-related high-frequency-induced synaptic strengthening (PubMed:25865831).|||cell cortex|||dendrite|||growth cone http://togogenome.org/gene/10090:Neu1 ^@ http://purl.uniprot.org/uniprot/O35657|||http://purl.uniprot.org/uniprot/Q3UL64 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A C-terminal internalization signal (YGTL) appears to allow the targeting of plasma membrane proteins to endosomes.|||Belongs to the glycosyl hydrolase 33 family.|||Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.|||Cell membrane|||Cytoplasmic vesicle|||Highly expressed in kidney, epididymis, followed by brain, spinal cord and weakly expressed in adrenal, heart, liver, lung and spleen.|||Interacts with cathepsin A (protective protein), beta-galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a multienzyme complex.|||Lysosome lumen|||Lysosome membrane|||N-glycosylated.|||Phosphorylation of tyrosine within the internalization signal results in inhibition of sialidase internalization and blockage on the plasma membrane. http://togogenome.org/gene/10090:Dnajb8 ^@ http://purl.uniprot.org/uniprot/Q9QYI7 ^@ Domain|||Function|||Subunit ^@ Efficient suppressor of aggregation and toxicity of disease-associated polyglutamine proteins.|||Interacts with histone deacetylases HDAC4, HDAC6, and SIRT2, HDAC activity is required for antiaggregation.|||The antiaggregation activity resides in the serine-rich region and the C-terminus. http://togogenome.org/gene/10090:Plin3 ^@ http://purl.uniprot.org/uniprot/Q9DBG5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the perilipin family.|||Cytoplasm|||Endosome membrane|||Homooligomer. Interacts with M6PR (via the cytoplasmic domain). Interacts with IGF2R (via the cytoplasmic domain).|||Lipid droplet|||Phosphorylation at Tyr-255 by isoform 1 of CHKA (CHKalpha2) promotes dissociation from lipid droplets: dissociation is followed by recruitment of autophagosome machinery to lipid droplets and subsequent lipid droplet lipolysis.|||Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets. Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network. http://togogenome.org/gene/10090:Slc7a8 ^@ http://purl.uniprot.org/uniprot/Q9QXW9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1 (PubMed:10574970). Functions as amino acid antiporter mediating the influx of extracellular essential amino acids mainly in exchange with the efflux of highly concentrated intracellular amino acids. Has relatively symmetrical selectivities but strongly asymmetrical substrate affinities at both the intracellular and extracellular sides of the transporter. This asymmetry allows SLC7A8 to regulate intracellular amino acid pools (mM concentrations) by exchange with external amino acids (uM concentration range), equilibrating the relative concentrations of different amino acids across the plasma membrane instead of mediating their net uptake. May play an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane (By similarity). Imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4) (PubMed:26601072, PubMed:28108384). Mediates the uptake of L-DOPA (By similarity). May participate in auditory function (PubMed:29355479).|||Basolateral cell membrane|||Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.|||Cell membrane|||Disulfide-linked heterodimer composed of the catalytic light chain subunit SLC7A8 and the heavy chain subunit SLC3A2 (PubMed:10574970). SLC3A2 acts as chaperones for correct plasma membrane trafficking and stabilization of SLC7A8 and modulates the substrate affinity and specificity of SLC7A8. ICAM-1 associates with the heterodimer SLC3A2/SLC7A8; facilitates leucine uptake (By similarity).|||Slc7a8-deficient mice present normal development and growth. Only a slightly altered coordination of movements is observed in Slc7a8-deficient mice. Circulating thyroid hormones, thyrotropin and thyroid hormone-responsive genes remain unchange. Functional compensation by other amino acid transporters might explain the lack of a severe phenotype (PubMed:21726201). The lack of Slc7a8 results in a significant increase of cataracts in old animals, in particularly in old females (PubMed:31231240). Slc7a8-deficient mice dysplay a hearing loss defect with incomplete penetrance affecting mainly high-frequency sounds, hearing loss severity increases with age in Slc7a8-deficient mice (PubMed:29355479).|||Strongly expressed in kidney and small intestine. Moderately present in placenta, ovary and brain (PubMed:10574970, PubMed:29355479). Expressed in the inner ear (PubMed:29355479). http://togogenome.org/gene/10090:Lhfpl4 ^@ http://purl.uniprot.org/uniprot/Q5U4E0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LHFP family.|||Contradictory results have been described and may be due to differences in the methods used for gene disruption (PubMed:28978485, PubMed:29742426). No visible phenotype, mice are viable and fertile until adulthood (PubMed:28978485). However cultured hippocampal neurons from deficient mice shown a dramatic decrease in both amplitude and frequency of miniature inhibitory postsynaptic currents (mIPSC) (PubMed:28978485). In contrast, deficient mice exhibit profound impairment of inhibitory synapse formation, prominent motor behavioral deficits and premature death (PubMed:29742426).|||Highly expressed in the brain, including the cortex, hippocampus, midbrain, olfactory bulb pona plus medulla (at protein level) (PubMed:26964900, PubMed:28279354, PubMed:29742426). Expressed in the in the cerebellar granular layer and in granular layer. Colocalized with GPHN at inhibitory synapses (PubMed:29742426). Weakly expressed in heart, testis, lung, intestine, vagina, ovary and uterus (PubMed:26964900).|||Interacts with GABA(A) receptor subunits (PubMed:28279354, PubMed:28978485, PubMed:29742426). Interacts with GABRB3 (PubMed:28978485). Interacts with GABRA2 (PubMed:28978485). Interacts with GABRG2 (PubMed:28978485, PubMed:29742426). Interacts with GABRA1 (PubMed:29742426). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with NLGN2; leading to mutual regulation of protein level and synaptic clustering (PubMed:29742426, PubMed:28978485).|||Plays a role in the regulation of inhibitory synapse formation and function by being involved in maintening gamma-aminobutyric acid receptors (GABAARs) clustering and their associated scaffold proteins at inhibitory synaptic sites (PubMed:28978485, PubMed:28279354, PubMed:29742426). Acts in concert with NLGN2 to recruit or stabilize GABAARs (PubMed:29742426).|||Postsynaptic cell membrane|||dendrite http://togogenome.org/gene/10090:Pmp22 ^@ http://purl.uniprot.org/uniprot/P16646|||http://purl.uniprot.org/uniprot/Q5SXS3 ^@ Caution|||Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A defect in Pmp-22 is the cause of trembler (tr) phenotype. Trembler mice show a Schwann cells defect characterized by severe hypomyelination and continuing Schwann cells proliferation throughout life.|||Belongs to the PMP-22/EMP/MP20 family.|||Cell membrane|||Expressed from day 3 of gastrulation, expression levels are maintained until day 10.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Might be involved in growth regulation, and in myelinization in the peripheral nervous system.|||Schwann cells of the peripheral nervous system (PubMed:1552943). Expressed at growth arrest of mammalian fibroblasts (PubMed:1692961).|||Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation. http://togogenome.org/gene/10090:Or2w3b ^@ http://purl.uniprot.org/uniprot/Q5NCD6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp668 ^@ http://purl.uniprot.org/uniprot/Q8K2R5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation. May play a role in DNA repair process.|||Nucleus http://togogenome.org/gene/10090:Prr11 ^@ http://purl.uniprot.org/uniprot/Q8BHE0 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Cytoplasm|||Plays a critical role in cell cycle progression.|||Ubiquitinated. Rapidly degraded by the proteasome; degradation may involve FBXW7-specific phosphorylated phosphodegron motifs. http://togogenome.org/gene/10090:Dnaaf4 ^@ http://purl.uniprot.org/uniprot/E9Q973|||http://purl.uniprot.org/uniprot/Q8C5Z6|||http://purl.uniprot.org/uniprot/Q8R368 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Dynein axonemal particle|||Interacts with ZMYND10 (By similarity). Interacts with ESR1 and ESR2. Interacts with STUB1 (By similarity). Interacts with DNAAF2 (By similarity). Interacts with CCT3, CCT4, CCT5 and CCT8 (PubMed:23872636). Interacts with DNAAF6/PIH1D3 (By similarity).|||Involved in neuronal migration during development of the cerebral neocortex. May regulate the stability and proteasomal degradation of the estrogen receptors that play an important role in neuronal differentiation, survival and plasticity (By similarity). Axonemal dynein assembly factor required for ciliary motility.|||Nucleus|||neuron projection http://togogenome.org/gene/10090:Irf9 ^@ http://purl.uniprot.org/uniprot/E9PZJ2|||http://purl.uniprot.org/uniprot/E9Q8M6|||http://purl.uniprot.org/uniprot/Q3UKQ7|||http://purl.uniprot.org/uniprot/Q61179 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IRF family.|||By IFN-alpha and IFN-beta. Upon stimulation the regulatory phosphorylated alpha and beta subunits assemble with the gamma subunit and translocate from the cytoplasm to the nucleus.|||Interacts with STAT2 in the cytoplasm. Forms the interferon-stimulated gene factor 3 complex (ISGF3) with the heterodimer STAT1:STAT2; upon stimulation.|||Nucleus|||Transcription factor that plays an essential role in anti-viral immunity. It mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state. http://togogenome.org/gene/10090:Vmn1r47 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Y0|||http://purl.uniprot.org/uniprot/Q9EQ51 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Ift52 ^@ http://purl.uniprot.org/uniprot/Q62559 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ After opioid treatment, expression decreases.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:19253336). Interacts with IFT88 (PubMed:19253336). Interacts with TTC25 (PubMed:25860617). Interacts with TTC21A (By similarity). Interacts with IFT70A1, IFT70A2, IFT70B and KIF17 (PubMed:23810713). Interacts with USH1G (By similarity).|||Involved in ciliogenesis as part of a complex involved in intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia (PubMed:19253336). Required for the anterograde transport of IFT88 (By similarity).|||cilium http://togogenome.org/gene/10090:Vmn1r15 ^@ http://purl.uniprot.org/uniprot/Q14C10 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ntn4 ^@ http://purl.uniprot.org/uniprot/Q0VEM1|||http://purl.uniprot.org/uniprot/Q9JI33 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in kidney, liver, heart, ovary, testis, retina, brain, olfactory bulb, and widely expressed in embryo.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May form a homodimer.|||May play an important role in neural, kidney and vascular development. Promotes neurite elongation from olfactory bulb explants.|||basement membrane http://togogenome.org/gene/10090:Or5p62 ^@ http://purl.uniprot.org/uniprot/Q8VFD0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Helz2 ^@ http://purl.uniprot.org/uniprot/E9QAM5 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA2/NAM7 helicase family.|||Contains 5 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. These motifs are not required for interaction with PPARG (By similarity).|||Helicase that acts as a transcriptional coactivator for a number of nuclear receptors including PPARA, PPARG, THRA, THRB and RXRA.|||In 3T3-L1 cell line, highly expressed before differentiation with a slight decreased after the induction of adipocyte differentiation.|||Interacts with PPARA (via DNA-binding domain) and PPARG; the interaction stimulates the transcriptional activity of PPARA and PPARG. Interacts with THRAP3; the interaction is direct and HELZ2 and THRAP3 synergistically enhance the transcriptional activity of PPARG. It is probably part of the peroxisome proliferator activated receptor alpha interacting complex (PRIC).|||Nucleus http://togogenome.org/gene/10090:Ssr4 ^@ http://purl.uniprot.org/uniprot/Q3TVJ8|||http://purl.uniprot.org/uniprot/Q62186|||http://purl.uniprot.org/uniprot/Q9D8L3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAP-delta family.|||Endoplasmic reticulum membrane|||Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma.|||Membrane|||TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. http://togogenome.org/gene/10090:Mrpl16 ^@ http://purl.uniprot.org/uniprot/Q99N93 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL16 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Slc2a5 ^@ http://purl.uniprot.org/uniprot/Q9WV38 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Cell membrane|||Detected at the apical membrane of villi in the jejunum (PubMed:18496516, PubMed:19091748, PubMed:26071406). Detected in jejunum mucosa (PubMed:26071406). Detected in epididymis and whole testis (at protein level) (PubMed:18417103). Detected in small intestine, kidney and testis (PubMed:12031501, PubMed:18417103, PubMed:19091748). Detected in cochlea, but not in inner or outer cochlear hair cells (PubMed:18417103).|||Fructose uptake is inhibited by cytochalasin B.|||Functions as a fructose transporter that has only low activity with other monosaccharides (PubMed:12031501, PubMed:19091748). Can mediate the uptake of deoxyglucose, but with low efficiency (By similarity). Essential for fructose uptake in the small intestine (PubMed:19091748, PubMed:26071406). Plays a role in the regulation of salt uptake and blood pressure in response to dietary fructose (PubMed:19091748). Required for the development of high blood pressure in response to high dietary fructose intake (PubMed:19091748).|||Mice fed a standard diet appear normal and healthy, and display no visible phenotype (PubMed:18417103, PubMed:19091748, PubMed:26071406). Mutant mice show reduced food intake when kept on a high-frucose diet and about 28% reduction of their body weight within seven days. They loose more weight than wild-type mice that receive similar amounts of high-fructose food (PubMed:19091748). Mutant mice show strongly decreased fructose absorption in the jejunum (PubMed:19091748, PubMed:26071406). Contrary to wild-type, mutant mice have a strongly distended colon and caecum when kept on a high-fructose diet. Their intestines look normal when they are fed a standard diet. Contrary to wild-type, mutant mice do not display increased fructose levels in blood serum when kept on a high-fructose diet. Contrary to wild-type, they do not show increased salt absorption in response to fructose, and do not develop high blood pressure in response to fructose feeding. On the contrary, the blood pressure of mutant mice is strongly decreased after five days on a high-fructose diet. Mutant mice develop hypovolemic shock and die after 7 to 10 days on high-fructose diet (PubMed:19091748). Mutant mice display no defects of cochlear morphology or any hearing defects (PubMed:18417103).|||Up-regulated in jejunum by dietary fructose intake (at protein level) (PubMed:18496516). Up-regulated in jejunum by dietary fructose intake (PubMed:18496516, PubMed:26071406). Up-regulated by dietary fructose intake in small intestine and testis (PubMed:12031501).|||sarcolemma http://togogenome.org/gene/10090:Ufm1 ^@ http://purl.uniprot.org/uniprot/P61961 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UFM1 family.|||Cytoplasm|||Interacts with UBA5. Interacts with UFC1.|||Nucleus|||Ubiquitin-like modifier which can be covalently attached via an isopeptide bond to lysine residues of substrate proteins as a monomer or a lysine-linked polymer (PubMed:21494687). The so-called ufmylation, requires the UFM1-activating E1 enzyme UBA5, the UFM1-conjugating E2 enzyme UFC1, and the UFM1-ligase E3 enzyme UFL1. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress. Ufmylation of TRIP4 regulates nuclear receptors-mediated transcription (By similarity).|||Widely expressed with higher expression in secretory tissues (at protein level). http://togogenome.org/gene/10090:Tac4 ^@ http://purl.uniprot.org/uniprot/Q99N14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tachykinin family.|||Expressed in hematopoietic cells with highest levels in pre- and pro-B cells but not in later developmental stages. Also detected in uterus, skeletal muscle, brain, spleen, stomach, skin and lactating mammary gland and in cells of myeloid lineage including dendritic and microglial cells and macrophages. In uterus, highest expression is observed in non-pregnant diestrus mice and in day 5 pregnant mice. Compared with mice in diestrus, decreases 2.6-fold in uteri from non-pregnant mice in estrus and 10.2-fold in day 17 pregnant mice. Detected at sites of chronic inflammation such as granulomas.|||Secreted|||Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles. Hemokinin induces plasma extravasation, mast cell degranulation, muscle contraction, salivary secretion and scratching behavior. Increases sperm motility. Induces potent analgesic effects and may play a role in pain modulation. Promotes survival of bone marrow B lineage cells and of cultured LPS-stimulated pre-B cells and may act as an autocrine factor required for B-cell survival and proliferation. Lowers systemic arterial pressure following intravenous injection. Induces interferon-gamma production and may play a role in the inflammatory response. Shows potent affinity and specificity for the NK-1 receptor. http://togogenome.org/gene/10090:Gm20831 ^@ http://purl.uniprot.org/uniprot/Q3TTD8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Amt ^@ http://purl.uniprot.org/uniprot/A2RSW6|||http://purl.uniprot.org/uniprot/Q8CFA2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GcvT family.|||Mitochondrion|||The glycine cleavage system catalyzes the degradation of glycine.|||The glycine cleavage system is composed of four proteins: P, T, L and H. http://togogenome.org/gene/10090:Sohlh1 ^@ http://purl.uniprot.org/uniprot/Q6IUP1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Forms both hetero- and homodimers with SOHLH2.|||In male testis, it is expressed as early as 12.5 dpc. After birth, it localizes to type A spermatogonia in 7-day-old testis and adult testis, but not in spermatocytes. In spermatogonia, it is initially detected in stage IV Aal spermatogonia and strongly expressed in Aal, A1, A2, A3, A4, intermediate and type B spermatogonia (at protein level). In ovary, it is detected at 15.5 dpc, when oocytes have entered meiosis I, although a low level expression is detectable at 13.5 dpc. Expressed in oocytes of germ cell cysts as well as primordial follicles in the newborn ovary. In adult ovaries, it is preferentially expressed in primordial oocytes but disappear rapidly as the oocytes are recruited to form primary and secondary (multilayer and preantral) follicles. During oocyte differentiation, protein appearance at 15.5 dpc correlates with SOHLH2 translocation from the cytoplasm into the nucleus and is dependent on SOHLH2 expression (PubMed:28504655).|||In males, it is mainly expressed in testis, while in females it is mainly expressed in ovary. In testis, it is exclusively expressed in spermatogonia, with a preference for prespermatogonia and type A spermatogonia. In ovary, it is detected in germ cell cysts, primordial follicles, and primary follicles but is undetectable by the secondary follicle stage (at protein level). Expressed in the majority of spermatogonia in adult animals, but not in the most undifferentiated spermatogonial population (PubMed:22056784).|||Knockout mice are infertile. Males lacking SOHLH1 display disrupted spermatogonial differentiation into spermatocytes and show a strong down-regulation Lhx8 and Neurog3/Ngn3 genes (PubMed:16564520). Females display perturbed follicular formation, probably partially due to down-regulation of Nobox and Figla, 2 genes required for folliculogenesis (PubMed:16690745). Fertility could be restored by conditional expression of a SOHLH1 transgene after the onset of meiosis (PubMed:28504655).|||Nucleus|||Transcription is activated by DMRT1 in undifferentiated spermatogonia.|||Transcription regulator of both male and female germline differentiation. Suppresses genes involved in spermatogonial stem cells maintenance, and induces genes important for spermatogonial differentiation (PubMed:22056784). Coordinates oocyte differentiation without affecting meiosis I (PubMed:28504655). http://togogenome.org/gene/10090:2310057J18Rik ^@ http://purl.uniprot.org/uniprot/Q8C6C9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LEG1 family.|||May be involved in early liver development.|||Secreted http://togogenome.org/gene/10090:Olig3 ^@ http://purl.uniprot.org/uniprot/Q6PFG8 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ May determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons.|||Nucleus|||Restricted to the CNS. At 9.25 and 10.5 dpc, specifically expressed in the dorsal neural tube from the midbrain/hindbrain boundary to the spinal cord. At 10.5 dpc, expressed continuously from the upper rhombic lip to the tail. From 10.5 to 12.5 dpc, located in the most dorsal aspect of the spinal cord, excluding the roof plate, mainly in proliferating progenitor cells; quickly down-regulated in postmitotic neurons. At 11.5 dpc, 3 ventral expression clusters, corresponding to p3, p2 and p0 domains, transiently appear on the lateral margin of the subventricular zone, in addition to dorsal expression. At 14.5 dpc, weakly expressed in cells scattered in the mantle zone. Expression declines after 15.5 dpc. In the 11.5 dpc forebrain, expressed in the ventricular zone of the dorsal thalamus. In the 11.5 to 14.5 dpc hindbrain, dorsally expressed in the upper and lower rhombic lip, in the cerebellar neuroepithelium.|||Weakly expressed, mainly in non-neural tissues. http://togogenome.org/gene/10090:Zfp92 ^@ http://purl.uniprot.org/uniprot/Q62396 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Usp33 ^@ http://purl.uniprot.org/uniprot/A0A0H2UKB8|||http://purl.uniprot.org/uniprot/Q8R5K2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family. USP20/USP33 subfamily.|||Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Interacts with VHL, leading to its ubiquitination and subsequent degradation (By similarity). Interacts with ARRB1 and ARRB2 (By similarity). Interacts with ADRB2 (By similarity). Interacts with DIO2 (By similarity). Interacts with SELENBP1; in a selenium-dependent manner (By similarity). Interacts with CCP110 (By similarity). Interacts with ROBO1 (PubMed:19684588, PubMed:19706539). Interacts with ADRB2 (By similarity).|||Present in 9.5 and 11.5 dpc commissural neurons (at protein level).|||The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 55 is replaced by a Glu residue (By similarity).|||Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.|||centrosome|||perinuclear region http://togogenome.org/gene/10090:Neil3 ^@ http://purl.uniprot.org/uniprot/Q8K203 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FPG family.|||By mitogen stimulation in splenocytes, and by hypoxic-ischemic injury in the striatum and hippocampus.|||Chromosome|||DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). No activity on 8-oxoG detected (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:20185759, PubMed:22065741, PubMed:22569481, PubMed:22959434, PubMed:23305905, PubMed:23313161).|||Expressed in testis, thymus, spleen and bone marrow. In young mice, expressed at higher levels in thymocytes than splenocytes. At 12 dpc, abundant in the subventricular zone (SVZ) of the lateral ventricles. At 17.5 dpc and P0, expression is limited to distinct cells in the cortical SVZ, in cells of the secondary matrix, the dentate gyrus migratory route and the dentate gyrus.|||Highly expressed in the developing brain at 12 dpc-13 dpc when neurogenesis starts. Expression decreases during later development and is undetectable in adult brain.|||May be due to an intron retention.|||Nucleus|||Perinatal mice show reduced regeneration of neural tissue following ischemic brain damage (stroke), associated with fewer activated microglia and impaired neural stem cell proliferation. Aged mice show deficits in learning and memory, decreased anxiety-like behavior, and changes in hippocampal synapse composition. Otherwise viable and fertile.|||The N-terminal region (2-282) contains the glycosylase and lyase activities.|||The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template.|||Was originally thought to be inactive as a glycosylase, but recent reports demonstrate that cleavage of the initiator methionine is essential for catalytic activity. http://togogenome.org/gene/10090:Colec12 ^@ http://purl.uniprot.org/uniprot/Q8K4Q8 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in embryo at 9 dpc, increases progressively to a peak at 14 dpc and gradually decreases until 19 dpc.|||Expressed in vascular endothelial cells in the heart, in perivascular macrophage and smooth muscle cells. Expressed in plaques-surrounding reactive astrocytes located in cerebral cortex and hippocampus and in leptomeningeal vessels showing characteristics of cerebral amyloid angiopathy (CAA) in a double transgenic mouse model of Alzheimer disease (at protein level). Strongly expressed in lung. Moderately expressed in heart, skeletal muscle, spleen, liver, brain, colon, testis, stomach and kidney. Expressed in neonatal astrocytes. Expressed in reactive astrocytes and vascular/perivascular cells in the brain of a double transgenic mouse model of Alzheimer disease.|||Membrane|||Scavenger receptor that displays several functions associated with host defense. Promotes binding and phagocytosis of Gram-positive, Gram-negative bacteria and yeast. Binds also to sialyl Lewis X or a trisaccharide and asialo-orosomucoid (ASOR). Mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells (By similarity). Binds to several carbohydrates including Gal-type ligands, D-galactose, L- and D-fucose, GalNAc, T and Tn antigens in a calcium-dependent manner and internalizes specifically GalNAc in nurse-like cells (By similarity).|||The extracellular domain forms a stable trimer (By similarity). The extracellular domain interacts with fibrillar amyloid-beta peptide.|||Up-regulated in activated microglia and by fibrillar amyloid-beta peptide in activated astrocytes. http://togogenome.org/gene/10090:Vmn1r57 ^@ http://purl.uniprot.org/uniprot/K7N731 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trim2 ^@ http://purl.uniprot.org/uniprot/E9QKC6|||http://purl.uniprot.org/uniprot/Q3UHH4|||http://purl.uniprot.org/uniprot/Q9ESN6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, expressed in the developing nervous system, particularly in the spinal cord, dorsal rootganglia, hindbrain and midbrain.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||Forms homooligomers (By similarity). Interacts with TRIM3; this interaction reduces TRIM2 activity (By similarity). Interacts with myosin V; myosin V may not be a substrate for ubiquitination. Interacts with NEFL. Interacts with phosphorylated BCL2L11. Interacts with SIRPA (PubMed:30726215).|||Highly expressed in the cerebellum, hippocampus, retina and spinal cord. In the cerebellum, strongest expression in Purkinje cells and in the deep cerebellar nuclei. In retina, high expression in the ganglionic cell layer, inner nuclear layer and inthe outer plexiform layer. Particularly high expression in the hippocampus, in pyramidal cells of CA1-CA3 hippocampal areas and ingranule cells of the dentate gyrus.|||Mutant mice are indistinguishable from wild type until about 1.5 months of age, when they begin to show intention tremor, followed by gait ataxia. At this stage, neurons exhibit axonal swellings, which consist of the accumulation of disorganized neurofilaments and microtubules, mitochondria and vesicles. In later stages, mutant animals suffer from episodes of spontaneous generalized seizures, a phenotype caused by progressive loss of Purkinje cells through apoptosis. At 4 months of age, retinas in mutant mice display decreased thickness of the inner nuclear layer and a reduced number of ganglionic cells. The outer plexiform layer is also reduced, whereas the size of the photoreceptor layer is not altered (PubMed:18687884). In addition, TRIM2-knockout mice are also more susceptible to infection with new world arenaviruses (PubMed:30726215).|||RING-type zinc finger-dependent and UBE2D1-dependent autoubiquitination.|||The interaction with myosin V is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades.|||UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance. Plays a role in antiviral immunity and limits new world arenavirus infection independently of its ubiquitin ligase activity by decreasing virus internalization (PubMed:30726215). http://togogenome.org/gene/10090:Irs4 ^@ http://purl.uniprot.org/uniprot/Q9Z0Y7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2.|||Cell membrane|||Expressed in skeletal muscle, brain, heart, kidney and liver.|||First detected from days 15 and 17 embryos.|||Interacts with CRK and CRKL. Interaction with CRK is stronger than with CRKL. Interacts with CRK via the phosphorylated YXXM motifs. Interacts with PLC-gamma, SHC1, PTK6, PPP4C and NISCH (By similarity). Interacts with SOCS6 in response to stimulation with either insulin or IGF1. Interacts with PIK3R1 and GRB2.|||Phosphorylated on tyrosine residues in response to both insulin and IGF1 signaling. Phosphorylated on Tyr-894 in response to FGF2 signaling. Phosphorylation of Tyr-894 is required for GRB2, phospholipase C-gamma and phosphatidylinositol 3-kinase interaction (By similarity).|||Slight defects in growth, reproduction and glucose homeostasis. http://togogenome.org/gene/10090:Tubgcp4 ^@ http://purl.uniprot.org/uniprot/Q543T6|||http://purl.uniprot.org/uniprot/Q8BWR3|||http://purl.uniprot.org/uniprot/Q8BYN2|||http://purl.uniprot.org/uniprot/Q9D4F8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TUBGCP family.|||Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6. Interacts with NINL. Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome.|||Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.|||centrosome http://togogenome.org/gene/10090:Foxq1 ^@ http://purl.uniprot.org/uniprot/O70220 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Defects in Foxq1 are the cause of the satin (sa) phenotype and results in a silky coat with high sheen arising from structurally abnormal medulla cells and defects in differentiation of the hair shaft.|||Expressed in kidney and stomach. Expression in the outer medulla of the kidney and the transitional epithelium. Expressed in the hair follicle medulla.|||Nucleus|||Plays a role in hair follicle differentiation. http://togogenome.org/gene/10090:Or2b2 ^@ http://purl.uniprot.org/uniprot/Q7TQU5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmsb4x ^@ http://purl.uniprot.org/uniprot/P20065|||http://purl.uniprot.org/uniprot/Q6ZWX2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AcSDKP is inactivated by ACE, which removes the dipeptide Lys-Pro from its C-terminus.|||Belongs to the thymosin beta family.|||Identified in a complex composed of ACTA1, COBL, GSN AND TMSB4X (By similarity). Interacts with SERPINB1 (By similarity).|||Originally found in thymus but it is widely distributed in many tissues.|||Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.|||Potent inhibitor of bone marrow derived stem cell differentiation (By similarity). Acts by inhibits the entry of hematopoietic pluripotent stem cells into the S-phase (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Cybrd1 ^@ http://purl.uniprot.org/uniprot/Q925G2 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Binds 2 heme b groups non-covalently.|||By iron deficiency. Up-regulated in duodenal mucosa of mice lacking transferrin or Hfe (at protein level).|||Cell membrane|||Highly expressed in the brush-border membrane of duodenal enterocytes (at protein level). Also expressed in liver and spleen.|||Homodimer.|||Mice are normal and do not display iron stores defects, even in the setting of iron deficiency. These results, reported by PubMed:15961514, suggest that Cybrd1 is not an essential component of intestinal iron apparatus. However, according to PubMed:16326980, no direct measurements of iron absorption were made by PubMed:15961514, suggesting that final conclusions can be drawn only when direct iron absorption studies are carried out or mice are maintained on a diet containing ferric iron only.|||Plasma membrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) into Fe(2+) (PubMed:17068337). Probably functions in dietary iron absorption at the brush border of duodenal enterocytes by producing Fe(2+), the divalent form of iron that can be transported into enterocytes (PubMed:11230685, PubMed:12547225). It is also able to reduce extracellular monodehydro-L-ascorbate and may be involved in extracellular ascorbate regeneration by erythrocytes in blood (PubMed:17068337). May also act as a ferrireductase in airway epithelial cells (By similarity). May also function as a cupric transmembrane reductase (PubMed:18498772). http://togogenome.org/gene/10090:Glt6d1 ^@ http://purl.uniprot.org/uniprot/Q2NKH9 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Membrane http://togogenome.org/gene/10090:Cys1 ^@ http://purl.uniprot.org/uniprot/Q8R4T1 ^@ Developmental Stage|||Disease Annotation|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Defects in Cys1 are a cause of polycystic kidney disease.|||Expressed in the fetal kidney.|||Expressed primarily in the kidney and liver. Expressed at lower levels in the lung, brain and heart.|||Interacts (when myristoylated) with UNC119 and UNC119B; interaction is required for localization to cilium.|||cilium axoneme|||cilium membrane http://togogenome.org/gene/10090:Pawr ^@ http://purl.uniprot.org/uniprot/Q925B0 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homooligomer. Interacts (via the C-terminal region) with WT1. Interacts with THAP1. Interacts with AATF. Interacts with BACE1. Interacts with SPSB1 (via B30.2/SPRY domain); this interaction is direct and occurs in association with the Elongin BC complex (PubMed:16369487, PubMed:20561531). Interacts with SPSB2 (via B30.2/SPRY domain); this interaction occurs in association with the Elongin BC complex (PubMed:16369487, PubMed:20561531). Interacts with SPSB4 (via B30.2/SPRY domain); this interaction occurs in association with the Elongin BC complex (PubMed:16369487, PubMed:20561531). Component of a ternary complex composed of SQSTM1 and PRKCZ (By similarity). Interacts with actin (By similarity).|||Nucleus|||Preferentially phosphorylated at the Thr-156 by PKC in cancer cells.|||Pro-apoptotic protein capable of selectively inducing apoptosis in cancer cells, sensitizing the cells to diverse apoptotic stimuli and causing regression of tumors in animal models. Induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-kappa-B transcriptional activity. Inhibits the transcriptional activation and augments the transcriptional repression mediated by WT1. Down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1. Seems also to be a transcriptional repressor by itself. May be directly involved in regulating the amyloid precursor protein (APP) cleavage activity of BACE1 (By similarity).|||The B30.2/SPRY domain-binding motif mediates recognition by proteins containing a B30.2/SPRY domain.|||The SAC domain is a death-inducing domain selective for apoptosis induction in cancer cells. This domain is essential for nuclear entry, Fas activation, inhibition of NF-kappa-B activity and induction of apoptosis in cancer cells (By similarity).|||The leucine-zipper domain is not essential for apoptosis, but is required for sensitization of cells to exogenous apoptotic insults and for interaction with its partners.|||The synapses are crucial cellular sites for the cell death promoting actions of PAWR in motor neurons. Targeted inhibition of PAWR by RNAi is neuroprotective. http://togogenome.org/gene/10090:Sft2d2 ^@ http://purl.uniprot.org/uniprot/Q8VD57 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SFT2 family.|||May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.|||Membrane http://togogenome.org/gene/10090:Rapgef5 ^@ http://purl.uniprot.org/uniprot/Q8C0Q9 ^@ Function|||Subcellular Location Annotation ^@ Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation (By similarity).|||Nucleus http://togogenome.org/gene/10090:Tpbg ^@ http://purl.uniprot.org/uniprot/Q9Z0L0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Highly expressed in embryo and placenta. In adult, expressed only in brain and ovary. Not detected in kidney small intestine, heart, spleen, testis, liver, lung, thymus and stomach.|||Highly glycosylated.|||May function as an inhibitor of Wnt/beta-catenin signaling by indirectly interacting with LRP6 and blocking Wnt3a-dependent LRP6 internalization.|||The C-terminus of LRR N-terminal cap (LRRNT) and LRR 1 are essential for the inhibition of the Wnt signaling pathway. http://togogenome.org/gene/10090:Gm9839 ^@ http://purl.uniprot.org/uniprot/Q6IE03 ^@ Similarity ^@ Belongs to the peptidase C48 family. http://togogenome.org/gene/10090:Psmd5 ^@ http://purl.uniprot.org/uniprot/Q8BJY1 ^@ Domain|||Function|||Similarity|||Subunit ^@ Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5 (By similarity).|||Belongs to the proteasome subunit S5B/HSM3 family.|||Interacts with PSMC1, PSMC2, PSMD1 and PSMD6. Part of transient complex containing PSMD5, PSMC2, PSMC1 and PSMD2 formed during the assembly of the 26S proteasome.|||Rich in dileucine repeats, which have been implicated in trafficking of a variety of transmembrane proteins. http://togogenome.org/gene/10090:Adam22 ^@ http://purl.uniprot.org/uniprot/D3YUP9|||http://purl.uniprot.org/uniprot/D6QSS8|||http://purl.uniprot.org/uniprot/Q9R1V6 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in juxtaparanodal zones in the central nervous system and at nerve terminal plexuses of basket cells in the cerebellum (at protein level) (PubMed:20089912, PubMed:26269648). Expressed at high levels in the brain. Strongly expressed in cerebellar granule cells and hippocampus. In spinal cord, expression is restricted to gray matter.|||Interacts with LGI1 (PubMed:16990550, PubMed:18974846, PubMed:20089912). Can bind to LGI4 (PubMed:18974846). Interacts with KCNA2, DLG2 and DLG4 (PubMed:20089912). Interacts with ADAM11 (PubMed:26269648). Interacts (via C-terminus) with YWHAB/14-3-3 beta (By similarity). Interacts (via C-terminus) with YWHAZ/14-3-3 zeta (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice display severe ataxia within one week after birth and die before weaning, probably due to convulsions. They display marked hypomyelination of the peripheral nerves.|||Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Involved in regulation of cell adhesion and spreading and in inhibition of cell proliferation (By similarity). Neuronal receptor for LGI1.|||The precursor is cleaved by a furin endopeptidase.|||axon http://togogenome.org/gene/10090:Marchf9 ^@ http://purl.uniprot.org/uniprot/Q3TZ87 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin-protein ligase that may mediate ubiquitination of MHC-I, CD4 and ICAM1, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.|||Golgi apparatus membrane|||Homodimer.|||Lysosome membrane|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Steap4 ^@ http://purl.uniprot.org/uniprot/Q923B6 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STEAP family.|||By Tnfa (TNF-alpha), by Il6 in white and brown adipose tissue, and IL1B in white adipose tissue. Tnfa, Il6 and Il1b shows sinergistic stimulatory effects.|||Can also utilize the flavins FMN and riboflavin.|||Cell membrane|||Early endosome membrane|||Expressed in white and brown adipose tissues cells, as well as in muscle and liver cells. Detected in joints and spleens of arthritic mice.|||Golgi apparatus membrane|||Homotrimer. Interacts with PTK2/FAK1; the interaction may regulate PTK2 phosphorylation.|||Integral membrane protein that functions as NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane (PubMed:16609065). Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (By similarity). Can also reduce Cu(2+) to Cu(1+) (PubMed:16609065). Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses (PubMed:17482547). Associated with obesity and insulin-resistance (By similarity). Involved in inflammatory arthritis, through the regulation of inflammatory cytokines (PubMed:19660107). Inhibits anchorage-independent cell proliferation (By similarity).|||Mice are viable and fertile, but exhibit overt inflammation with increased expression of Il6, Tnfa, Ccl2, haptoglobin and Socs3 in visceral adipose tissue as well as macrophage infiltration. They develop metabolic disease on regular diet with insulin resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty liver disease. Adipocytes isolated from visceral fat exhibit severily defective glucose transport, with decreased expression of Slc2a4, Adipoq, Fas and Pparg. Glucose disposal is lower in response to insulin stimulation and hepatic glucose production is higher, confirming systemic and hepatic insulin-resistance. http://togogenome.org/gene/10090:Ing2 ^@ http://purl.uniprot.org/uniprot/Q9ESK4 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ING family.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with H3K4me3 and to a lesser extent with H3K4me2. Component of a mSin3A-like complex at least consisting of SIN3A, HDAC1, HDAC2, RBBP4/RbAp48, RBBP7/RbAp46, SAP30 and ING2.|||Nucleus|||Seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53. Component of a mSin3A-like corepressor complex, which is probably involved in deacetylation of nucleosomal histones. ING2 activity seems to be modulated by binding to phosphoinositides (PtdInsPs) (By similarity).|||Sumoylation enhances its association with SIN3A and is required for binding to some target gene promoters, this is the case for TMEM71.|||The PHD-type zinc finger mediates the binding to H3K4me3.|||The polybasic region (PBR) is responsive to the binding to phosphoinositides (PtdInsPs), including phosphatidylinositol 5-phosphate (PtdIns(5)P). http://togogenome.org/gene/10090:Copg2 ^@ http://purl.uniprot.org/uniprot/Q9QXK3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COPG family.|||COPI-coated vesicle membrane|||Golgi apparatus membrane|||Oligomeric complex. Binds to CDC42. Interacts with JAGN1. Interacts with TMED10 (via cytoplasmic domain).|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity).|||cytosol http://togogenome.org/gene/10090:Spdl1 ^@ http://purl.uniprot.org/uniprot/Q923A2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Spindly family.|||Interacts with KNTC1 and ZW10. These interactions appear weak and may be transient or indirect. Interacts with dynein intermediate chain and dynactin (DCTN1) (By similarity). Interacts with the catalytically active form of USP45 (By similarity).|||Monoubiquitinated with'Lys-48' linkage (By similarity). Deubiquitinated by USP45 (By similarity).|||Nucleus|||Required for the localization of dynein and dynactin to the mitotic kintochore. Dynein is believed to control the initial lateral interaction between the kinetochore and spindle microtubules and to facilitate the subsequent formation of end-on kinetochore-microtubule attachments mediated by the NDC80 complex. Also required for correct spindle orientation. Does not appear to be required for the removal of spindle assembly checkpoint (SAC) proteins from the kinetochore upon bipolar spindle attachment. Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (By similarity). Plays a role in cell migration (By similarity).|||centrosome|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Adamts3 ^@ http://purl.uniprot.org/uniprot/E9Q287|||http://purl.uniprot.org/uniprot/G3X9D2 ^@ Caution|||Cofactor|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular matrix http://togogenome.org/gene/10090:H2-M11 ^@ http://purl.uniprot.org/uniprot/Q85ZX0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Ilk ^@ http://purl.uniprot.org/uniprot/O55222 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A PH-like domain is involved in phosphatidylinositol phosphate binding.|||Autophosphorylated on serine residues.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cell membrane|||Highly expressed in lung, heart, kidney, liver, brain, spleen and skeletal muscle. Weakly expressed in testis.|||Interacts with the cytoplasmic domain of ITGB1. Could also interact with integrin ITGB2, ITGB3 and/or ITGB5. Interacts (via ANK repeats) with LIMS1 and LIMS2. Interacts with PARVA (via C-terminus) and PARVB; these compete for the same binding site (By similarity). Interacts probably also with TGFB1I1 (PubMed:16737959). Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1 (By similarity). Interacts with FERMT2 (PubMed:18483218). Interacts with LIMD2; leading to activate the protein kinase activity. Interacts with PXN/PAXILLIN (via LD motif 4). Interacts with CCDC25 (via cytoplasmic region); initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells (By similarity).|||Receptor-proximal protein kinase regulating integrin-mediated signal transduction. May act as a mediator of inside-out integrin signaling. Focal adhesion protein part of the complex ILK-PINCH. This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway. Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells. Regulates cell motility by forming a complex with PARVB. Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B.|||Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK. The protein kinase activity is stimulated by LIMD2.|||focal adhesion|||lamellipodium|||sarcomere http://togogenome.org/gene/10090:Nudt15 ^@ http://purl.uniprot.org/uniprot/Q8BG93 ^@ Cofactor|||Function|||Induction|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the Nudix hydrolase family.|||Has the ability to complement a mutation of mutT in E.coli and thereby completely suppress the increased frequency of spontaneous mutations.|||Homodimer. Interacts with PCNA; interaction is disrupted in response to UV irradiation.|||Magnesium may be the real cofactor in vivo.|||May catalyze the hydrolysis of nucleoside triphosphates including dGTP, dTTP, dCTP, their oxidized forms like 8-oxo-dGTP and the prodrug thiopurine derivatives 6-thio-dGTP and 6-thio-GTP (PubMed:12767940). Could also catalyze the hydrolysis of some nucleoside diphosphate derivatives (By similarity). Hydrolyzes oxidized nucleosides triphosphates like 8-oxo-dGTP in vitro, but the specificity and efficiency towards these substrates are low. Therefore, the potential in vivo sanitizing role of this enzyme, that would consist in removing oxidatively damaged forms of nucleosides to prevent their incorporation into DNA, is unclear (PubMed:12767940). Through the hydrolysis of thioguanosine triphosphates may participate in the catabolism of thiopurine drugs (By similarity). May also have a role in DNA synthesis and cell cycle progression by stabilizing PCNA (By similarity). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (PubMed:32432673).|||Progressive reduction of protein levels after 4 month of age in the hippocampus of SAMP8 mouse, a mouse with early aging syndrome and reduced ability of learning and memory. http://togogenome.org/gene/10090:Phkg1 ^@ http://purl.uniprot.org/uniprot/P07934 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity).|||Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin.|||The two calmodulin-binding domains appear to act in concert to bind a single molecule of calmodulin and are pseudosubstrate/autoinhibitory domains. http://togogenome.org/gene/10090:Sertm1 ^@ http://purl.uniprot.org/uniprot/Q8CD78 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Spart ^@ http://purl.uniprot.org/uniprot/Q8R1X6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with ITCH and WWP1. Interacts (via MIT domain) with IST1; leading to the recruitment of SPART to midbodies.|||May be implicated in endosomal trafficking, or microtubule dynamics, or both. Participates in cytokinesis.|||Midbody|||Ubiquitinated; ubiquitination does not require ITCH and WWP1. http://togogenome.org/gene/10090:Wiz ^@ http://purl.uniprot.org/uniprot/O88286 ^@ Developmental Stage|||Domain|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:9795207, isoform L and isoform S are brain-specific. According to PubMed:16702210, isoform S is ubiquitously expressed.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||C57BL/6J and C57BR/cdJ mice specifically present an insertion of a type II early transposon in the opposite orientation into exon 6. This results in a strong reduction in the protein levels of isoform L.|||Isoform L and isoform S are expressed in brain from 14 dpc to adulthood, with highest levels in the perinatal period. At embryonic stages, isoform L seems to be excluded from cerebellum.|||May link EHMT1 and EHMT2 histone methyltransferases to the CTBP corepressor machinery. May be involved in EHMT1-EHMT2 heterodimer formation and stabilization.|||Nucleus|||Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). Interacts with EHMT1, EHMT2, CTBP1 and CTBP2.|||The C2H2-type zinc finger 10 mediates interaction with EHMT1 and EHMT2. http://togogenome.org/gene/10090:Fars2 ^@ http://purl.uniprot.org/uniprot/G3X9Q4|||http://purl.uniprot.org/uniprot/Q99M01 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Is responsible for the charging of tRNA(Phe) with phenylalanine in mitochondrial translation. To a lesser extent, also catalyzes direct attachment of m-Tyr (an oxidized version of Phe) to tRNA(Phe), thereby opening the way for delivery of the misacylated tRNA to the ribosome and incorporation of ROS-damaged amino acid into proteins (By similarity).|||Mitochondrion|||Mitochondrion matrix|||Monomer. http://togogenome.org/gene/10090:Rasa2 ^@ http://purl.uniprot.org/uniprot/P58069 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4) and phospholipids. http://togogenome.org/gene/10090:Pygo1 ^@ http://purl.uniprot.org/uniprot/Q9D0P5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with BCL9 via The PHD-type zinc finger motiv, and thereby becomes part of the nuclear beta-catenin/TCF complex. Found in a complex with BCL9L, CDC73, CTNNB1 and PYGO1. Interacts with histone H3 mono-, di- or tri-methylated at 'Lys4' (H3K4me1, H3K4me2, H3K4me3); the interaction is enhanced by the interaction with BCL9 (By similarity).|||Involved in signal transduction through the Wnt pathway.|||Nucleus http://togogenome.org/gene/10090:Trrap ^@ http://purl.uniprot.org/uniprot/E9QLK7 ^@ Similarity ^@ Belongs to the PI3/PI4-kinase family. TRA1 subfamily. http://togogenome.org/gene/10090:Ctla4 ^@ http://purl.uniprot.org/uniprot/P09793|||http://purl.uniprot.org/uniprot/Q5SSM0|||http://purl.uniprot.org/uniprot/Q6GTR6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2. Interacts with ICOSLG.|||Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.|||Membrane|||N-glycosylation is important for dimerization.|||Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.|||Widely expressed with highest levels in lymphoid tissues. http://togogenome.org/gene/10090:Bbs1 ^@ http://purl.uniprot.org/uniprot/Q3V3N7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Mice are anosmic (inability to perceive odors) and have defective olfactory cilia. Significant reduction in olfactory sensory neurons ciliation in the olfactory epithelium with decreased cilium length and number. Impaired cilium localization of the BBSome complex.|||Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with the C-terminus of RAB3IP. Interacts with CCDC28B and ALDOB. Interacts with PKD1.|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly (By similarity). Plays a role in olfactory cilium biogenesis/maintenance and trafficking and is essential for the localization of the BBSome complex in the olfactory sensory neurons cilia (PubMed:15322545, PubMed:28237838).|||centriolar satellite|||cilium membrane http://togogenome.org/gene/10090:Rhbdd1 ^@ http://purl.uniprot.org/uniprot/Q8BHC7 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S54 family.|||Endoplasmic reticulum membrane|||Expressed in testis (at protein level). Expressed in intestine, lung, brain, kidney, epididymis, stomach, muscle, spleen, liver, heart and testis.|||Inhibited by aprotinin.|||Interacts with BIK and STEAP3 (By similarity). Interacts (via C-terminal domain) with VCP/P97. Interacts with ubiquitin and ubiquitinated proteins.|||Intramembrane-cleaving serine protease that cleaves single transmembrane or multi-pass membrane proteins in the hydrophobic plane of the membrane, luminal loops and juxtamembrane regions. Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded membrane proteins. Required for the degradation process of some specific misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Functions in BIK, MPZ, PKD1, PTCRA, RHO, STEAP3 and TRAC processing. Involved in the regulation of exosomal secretion; inhibits the TSAP6-mediated secretion pathway. Involved in the regulation of apoptosis; modulates BIK-mediated apoptotic activity. Also plays a role in the regulation of spermatogenesis; inhibits apoptotic activity in spermatogonia.|||Mitochondrion membrane|||One study reported that the protein is not localized in the mitochondrion. http://togogenome.org/gene/10090:Stambp ^@ http://purl.uniprot.org/uniprot/Q9CQ26 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M67C family.|||Binds 2 Zn(2+) ions per subunit.|||Cytoplasm|||Early endosome|||Expressed in brain.|||Highest expression at 18.5 dpc, followed by a gradual decrease.|||Inhibited by N-ethylmaleimide.|||Interacts with STAM. Interacts with SMAD6 and SMAD7. Interacts with CHMP3; the interaction appears to relieve the autoinhibition of CHMP3. Interacts with SMURF2 and RNF11; this interaction promotes ubiquitination.|||Membrane|||Mice show a loss of neurons and apoptotic cells in the hippocampus.|||Nucleus|||Phosphorylated after BMP type I receptor activation.|||The JAMM motif is essential for the protease activity.|||Ubiquitinated by SMURF2 in the presence of RNF11.|||Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not cleave 'Lys-48'-linked polyubiquitin chains. Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF. Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7. Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes. Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization. Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways. http://togogenome.org/gene/10090:Vmn1r120 ^@ http://purl.uniprot.org/uniprot/K7N6J6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pik3r4 ^@ http://purl.uniprot.org/uniprot/Q8VD65 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG (PubMed:23332761). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1, AMBRA1 and NRBF2 (By similarity). PI3KC3-C1 probably associates with PIK3CB (PubMed:21059846). Interacts with RAB7A in the presence of PIK3C3/VPS34 (By similarity). Interacts with NRBF2 (By similarity).|||Late endosome|||Membrane|||Myristoylated.|||Probably autophosphorylated.|||Regulatory subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (By similarity).|||autophagosome http://togogenome.org/gene/10090:Atg4d ^@ http://purl.uniprot.org/uniprot/Q8BGV9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C54 family.|||Cleaved by CASP3 during apoptosis which leads to increased activity. The cleavage by CASP3 reveals a cryptic mitochondrial targeting sequence immediately downstream of their canonical caspase cleavage sites which leads to mitochondrial import of the protein.|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:33795848). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine (By similarity). Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy (By similarity). In addition to the protease activity, also mediates delipidation of ATG8 family proteins (PubMed:33795848). Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (PubMed:33795848). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) (By similarity). ATG4D plays a role in the autophagy-mediated neuronal homeostasis in the central nervous system (PubMed:33795848). Compared to other members of the family (ATG4A, ATG4B or ATG4C), constitutes the major protein for the delipidation activity, while it promotes weak proteolytic activation of ATG8 proteins (PubMed:33795848). Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy (By similarity).|||Cytoplasm|||Inhibited by N-ethylmaleimide.|||Mice develop normally and are born at the expected Mendelian ration (PubMed:33795848). Cells display accumulation of lipidated forms of ATG8 family proteins, affecting autophagosome number and size without significantly altering autophagic flux (PubMed:33795848). Mice show cerebellar neurodegeneration and impaired motor coordination, whose severity increases with age (PubMed:33795848).|||Mitochondrion matrix|||Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability.|||The cryptic mitochondrial transit peptide is revealed after cleavage by caspase upon oxidative stress and cell death. It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria. http://togogenome.org/gene/10090:Syce1 ^@ http://purl.uniprot.org/uniprot/Q9D495 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SYCE family.|||Chromosome|||Expressed in testis at 14 dpc and in oocytes at 18 dpc.|||Homodimer (PubMed:15944401). Found in a complex with SYCP1 and SYCE2 (PubMed:15944401). Interacts with SYCP1, SYCE2 and SYCE3 (PubMed:15944401, PubMed:21637789, PubMed:16968740). Interacts with SIX6OS1 (PubMed:27796301).|||Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase (PubMed:15944401). Requires SYCP1 in order to be incorporated into the central element (PubMed:15944401, PubMed:16968740). May have a role in the synaptonemal complex assembly, stabilization and recombination (PubMed:15944401).|||Meiotic cells (at protein level). Expressed in the ovary and testis.|||Nucleus http://togogenome.org/gene/10090:Gm21427 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Med14 ^@ http://purl.uniprot.org/uniprot/A2ABV5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 14 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with AR, ESR1, SREBF1 and STAT2 (By similarity). Interacts with GATA1.|||Nucleus http://togogenome.org/gene/10090:Atp8b3 ^@ http://purl.uniprot.org/uniprot/Q6UQ17 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Developmentally regulated in testis. Expression is first detected at 17 days after birth and is later up-regulated up to adulthood amd maintained thereafter.|||Disrupted normal fertilization by sperm; sensitivity to sperm concentration and the time required to fertilize an egg is increased; the number of spermatozoa bound to zona pellucida is decreased.|||Endoplasmic reticulum membrane|||Expressed in testis, specifically in spermatids within seminiferous tubules (at protein level).|||P4-ATPase flippase which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:14975727, PubMed:19017724). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules (PubMed:14975727). May be responsible for the maintenance of asymmetric distribution of phosphatidylserine (PS) in spermatozoa membranes (PubMed:14975727). Involved in acrosome reactions and binding of spermatozoa to zona pellucida (PubMed:19017724).|||acrosome membrane http://togogenome.org/gene/10090:Serpinb9b ^@ http://purl.uniprot.org/uniprot/Q9DAV6 ^@ Similarity ^@ Belongs to the serpin family. Ov-serpin subfamily. http://togogenome.org/gene/10090:Or1j13 ^@ http://purl.uniprot.org/uniprot/Q8VGK9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrp8 ^@ http://purl.uniprot.org/uniprot/A0A571BE60|||http://purl.uniprot.org/uniprot/B1AXJ4|||http://purl.uniprot.org/uniprot/B1AXJ5|||http://purl.uniprot.org/uniprot/F6YZZ8 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Tmem50b ^@ http://purl.uniprot.org/uniprot/Q9D1X9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UPF0220 family.|||Detected in cortical plate, trigeminal ganglion, dorsal root ganglia and the spinal cord at embryonic stage 14.5 dpc. Widely expressed in brain at postnatal day 7 including cortex, olfactory bulb, hippocampus and cerebellum. Expressed throughout layers II-VI of the cortex. In the olfactory bulb, has strongest expression in glomerular and mitral cell layers. In hippocampus, localizes to CA1, CA2, CA3 and dentate gyrus regions. In cerebellum, mainly expressed in the internal granule cell layer and the Purkinje cell layer.|||Endoplasmic reticulum membrane|||Expressed in brain, heart and testis (at protein level). In the cerebellum, has particularly strong expression in Bergmann astroglial cells (at protein level).|||Golgi apparatus membrane|||May form homotrimers or homodimers. http://togogenome.org/gene/10090:Gtf3c5 ^@ http://purl.uniprot.org/uniprot/Q3UI98|||http://purl.uniprot.org/uniprot/Q8R2T8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIIC subunit 5 family.|||Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters (By similarity).|||Nucleus|||Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with BRF1, GTF3C6 and TBP (By similarity). http://togogenome.org/gene/10090:Lmo2 ^@ http://purl.uniprot.org/uniprot/P25801 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state.|||Expressed in early mouse development in central nervous system, lung, kidney, liver and spleen but only very low levels occur in thymus.|||Interacts with BEX2 and KDM5A (By similarity). Interacts via its LIM domains with ELF2 and LDB1. Also interacts with basic helix-loop-helix protein TAL1/SCL and can assemble in a complex with LMO2 and TAL1/SCL.|||Nucleus|||The second LIM zinc-binding domain interacts with KDM5A. http://togogenome.org/gene/10090:Trhr ^@ http://purl.uniprot.org/uniprot/P21761|||http://purl.uniprot.org/uniprot/Q32MS1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for thyrotropin-releasing hormone (TRH). Upon ligand binding, this G-protein-coupled receptor triggers activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway. http://togogenome.org/gene/10090:Tmub1 ^@ http://purl.uniprot.org/uniprot/Q9JMG3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in adult brain; at protein level (PubMed:18665261, PubMed:20582322). Isoform 1 (lHOPS) is highly expressed in small intestine, stomach and epididymis. Isoform 2 (sHOPS) and iHOPS are abundantly expressed in brain, liver and adrenal gland (PubMed:24240191).|||Interacts with EEF1A1, CAMLG, GRIA2 and GRIP1. Interacts with NPM1 and CDKN2A; TMUB1 can enhance interaction between NPM1 and CDKN2A and is proposed to bridge the proteins; proposed to be mediated by iHOPS (PubMed:16014383, PubMed:18665261, PubMed:20582322, PubMed:22890319, PubMed:24240191). Interacts with TUBG1 (By similarity). Interacts with ERLIN2 and AMFR; TMUB1 promotes the interaction of ERLIN2 with AMFR (By similarity).|||Involved in sterol-regulated ubiquitination and degradation of HMG-CoA reductase HMGCR (By similarity). Involved in positive regulation of AMPA-selective glutamate receptor GRIA2 recycling to the cell surface (By similarity). Acts as negative regulator of hepatocyte growth during regeneration (By similarity).|||Isoform 1 (lHOPS) is processed by regulated intramembrane proteolysis (RIP) in the N-terminus to release iHOPS from membranes.|||Isoform 2 seems to undergo a selective cleavage in the C-terminal region to release an additional cytoplasmic form.|||May contribute to the regulation of translation during cell-cycle progression. May contribute to the regulation of cell proliferation (PubMed:16014383). May be involved in centrosome assembly (PubMed:18418082). Modulates stabilization and nucleolar localization of tumor suppressor CDKN2A and enhances association between CDKN2A and NPM1 (PubMed:22890319).|||Membrane|||Nucleus|||Postsynaptic cell membrane|||Recycling endosome|||Strong increase in home cage locomotor activity during the dark phase (subjective day) of the light:dark (L:D) cycle. There were no changes in activity during the light period and in locomotor activity observed in other assays, e.g. novel open-field.|||Up-regulated in regenerating liver.|||centrosome|||nucleolus http://togogenome.org/gene/10090:Pank4 ^@ http://purl.uniprot.org/uniprot/Q80YV4 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activity is strongly promoted by Co(2+), Ni(2+), Mg(2+) and Mn(2+). Activity is inhibited by EDTA.|||Cytoplasm|||Despite belonging to the type II pantothenate kinase family, the pantothenate kinase domain contains a Val residue at position 147 and a Trp residue at position 211 instead of the two conserved active site residues, Glu and Arg. Lacks pantothenate kinase activity.|||Expressed in liver, kidney, brain cortex and eye lens (at protein level).|||Homodimer. Interacts with PKM.|||In the C-terminal section; belongs to the damage-control phosphatase family. Phosphopantetheine phosphatase II subfamily.|||In the N-terminal section; belongs to the type II pantothenate kinase family.|||Knockout mice have a body weight and a lifespan similar to wild-type animals. About 10% of the animals start developing cataract at 2 months. At 15 months, 50% homozygous animals are affected. Heterozygous animals develop cataract later, with 10% animals affected at 9 months and 25% at 15.|||Phosphatase which shows a preference for 4'-phosphopantetheine and its oxidatively damaged forms (sulfonate or S-sulfonate), providing strong indirect evidence that the phosphatase activity pre-empts damage in the coenzyme A (CoA) pathway. Hydrolyzing excess 4'-phosphopantetheine could constitute a directed overflow mechanism to prevent its oxidation to the S-sulfonate, sulfonate, or other forms. Hydrolyzing 4'-phosphopantetheine sulfonate or S-sulfonate would forestall their conversion to inactive forms of CoA and acyl carrier protein. May play a role in the physiological regulation of CoA intracellular levels.|||Subfamily II proteins have an EGMGR motif about 50 residues from the C-terminus (By similarity). This motif lies near the metal-binding residues in the putative substrate-binding cleft 2 (By similarity). Subfamily II proteins occur only in eukaryotes, in two forms: as a stand-alone unit in plants, and as a C-terminal domain of pantothenate kinases in plants, animals, and chytrid fungi (By similarity). http://togogenome.org/gene/10090:Rcc1l ^@ http://purl.uniprot.org/uniprot/Q9CYF5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At E8.5, broadly expressed in yolk sac placenta, decidua, and embryo, with highest levels found in the trophoblast giant cells (TGCs) and ectoplacental cone (at protein level).|||Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA. Interacts with 16S mt-rRNA; this interaction is direct (By similarity). Interacts with OPA1; this interaction is direct (PubMed:28746876).|||Guanine nucleotide exchange factor (GEF) for mitochondrial dynamin-related GTPase OPA1. Activates OPA1, by exchanging bound GDP for free GTP, and drives OPA1 and MFN1-dependent mitochondrial fusion (PubMed:28746876). Plays an essential role in mitochondrial ribosome biogenesis. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation of core subunits of the oxidative phosphorylation system (By similarity).|||Mitochondrion inner membrane|||The RCC1-like repeats assemble into a circular seven-bladed beta propeller structure. Each blade is composed of four antiparallel beta-strands with loops between each strand. http://togogenome.org/gene/10090:Hsd17b13 ^@ http://purl.uniprot.org/uniprot/Q8VCR2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum|||Expressed predominantly in the liver (at protein level).|||Lipid droplet|||Plays a pivotal role in hepatic lipid metabolism. In vitro, it catalyzes the oxidation of a variety of lipid substrates, including 17beta-estradiol, retinol, retinal, and leukotriene B4. http://togogenome.org/gene/10090:Agap3 ^@ http://purl.uniprot.org/uniprot/F8VQE9|||http://purl.uniprot.org/uniprot/Q8BV81 ^@ Similarity ^@ Belongs to the centaurin gamma-like family. http://togogenome.org/gene/10090:Htatsf1 ^@ http://purl.uniprot.org/uniprot/Q8BGC0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HTATSF1 family.|||Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts with GTF2F2/RAP30 and POLR2A. Interacts with SF3A2/SAP62 and the spliceosomal U small nuclear ribonucleoproteins (snRNPs) (By similarity). Interacts with TCERG1/CA150.|||Functions as a general transcription factor playing a role in the process of transcriptional elongation. May mediate the reciprocal stimulatory effect of splicing on transcriptional elongation (By similarity).|||Nucleus|||The RRM domains mediate interaction with U snRNPs. http://togogenome.org/gene/10090:Wfdc1 ^@ http://purl.uniprot.org/uniprot/Q9ESH5 ^@ Function|||Subcellular Location Annotation ^@ Has growth inhibitory activity.|||Secreted http://togogenome.org/gene/10090:Ddo ^@ http://purl.uniprot.org/uniprot/A0A1L1SS55|||http://purl.uniprot.org/uniprot/A0A1L1SS65|||http://purl.uniprot.org/uniprot/Q2UVA9|||http://purl.uniprot.org/uniprot/Q922Z0|||http://purl.uniprot.org/uniprot/Q9CYP3|||http://purl.uniprot.org/uniprot/Q9D2B4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DAMOX/DASOX family.|||Peroxisome|||Selectively catalyzes the oxidative deamination of D-aspartate and its N-methylated derivative, N-methyl D-aspartate. http://togogenome.org/gene/10090:Ccdc59 ^@ http://purl.uniprot.org/uniprot/Q8R2N0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAP26 family.|||Component of the transcription complexes of the pulmonary surfactant-associated protein-B (SFTPB) and -C (SFTPC). Enhances homeobox protein Nkx-2.1-activated SFTPB and SFTPC promoter activities (By similarity).|||Interacts with NKX2-1.|||Nucleus http://togogenome.org/gene/10090:Atm ^@ http://purl.uniprot.org/uniprot/B9EHX4|||http://purl.uniprot.org/uniprot/Q62388 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation, on DNA damage, is required for activation of the kinase activity, dimer-monomer transition, and subsequent autophosphorylation on Ser-1987. Acetylated in vitro by KAT5/TIP60. Deacetylated by SIRT7 during the late stages of DNA damage response, promoting ATM dephosphorylation and subsequent deactivation.|||Atm-disrupted mice recapitulate the human ataxia telangiectasia phenotype. Mice homozygous for the disrupted Atm allele display growth retardation, neurologic dysfunction, male and female infertility secondary to the absence of mature gametes, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation.|||Belongs to the PI3/PI4-kinase family. ATM subfamily.|||Cytoplasmic vesicle|||Expressed in brain, skeletal muscle, testis, followed by spleen, lung, kidney, heart, liver and thymus. Ubiquitously expressed in embryonal tissues.|||Highest expression in embryonic central nervous system, from 13.5 dpc day and during the whole cerebellar development. Decreased expression when maturation occurs.|||Homodimer (By similarity). Dimers or tetramers in inactive state. On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active. Binds DNA ends, p53/TP53, ABL1, BRCA1, NBN/nibrin and TERF1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. DNA damage promotes association with RAD17. Interacts with EEF1E1; the interaction, induced on DNA damage, up-regulates TP53. Interacts with DCLRE1C, MYST1, KAT5, NABP2, ATMIN and CEP164 (By similarity). Interacts with AP2B1 and AP3B2; the interaction occurs in cytoplasmic vesicles (PubMed:9707615). Interacts with TELO2 and TTI1. Interacts with DDX1 (By similarity). Interacts with BRAT1 (By similarity). Interacts with CYREN (via XLF motif) (PubMed:30017584). Interacts (via microbody targeting signal) with PEX5; promoting translocation to peroxisomes in response to reactive oxygen species (ROS) (By similarity).|||Inhibited by wortmannin.|||Nucleus|||Peroxisome matrix|||Phosphorylated by NUAK1/ARK5 (By similarity). Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.|||Phosphorylated by NUAK1/ARK5. Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase. During the late stages of DNA damage response, dephosphorylated following deacetylation by SIRT7, leading to ATM deactivation.|||Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:19047460). Recognizes the substrate consensus sequence [ST]-Q (PubMed:19047460). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (PubMed:11571274). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes (By similarity). After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele (PubMed:19448632). Also involved in signal transduction and cell cycle control (By similarity). May function as a tumor suppressor (By similarity). Necessary for activation of ABL1 and SAPK (By similarity). Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (By similarity). May play a role in vesicle and/or protein transport (By similarity). Could play a role in T-cell development, gonad and neurological function (By similarity). Binds DNA ends (By similarity). Plays a role in replication-dependent histone mRNA degradation (By similarity). Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (By similarity). Phosphorylates ATF2 which stimulates its function in DNA damage response (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (By similarity). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (By similarity). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (By similarity).|||Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9, UBQLN4 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Binds DNA ends. Plays a role in replication-dependent histone mRNA degradation. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks.|||The FATC domain is required for interaction with KAT5.|||centrosome http://togogenome.org/gene/10090:Amot ^@ http://purl.uniprot.org/uniprot/Q8VHG2 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Motus' means 'motility' in Latin.|||Belongs to the angiomotin family.|||Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with MAGI1 and angiostatin (By similarity).|||Expressed in brain, skeletal muscle and placenta.|||Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions (By similarity).|||Polyubiquitinated by NEDD4, NEDD4L and ITCH, leading to proteasomal degradation.|||The angiostatin binding domain (850-1047) allows the binding to angiostatin.|||The coiled coil domain interacts directly with the BAR domain of ARHGAP17.|||tight junction http://togogenome.org/gene/10090:Tgfbi ^@ http://purl.uniprot.org/uniprot/A1L353|||http://purl.uniprot.org/uniprot/P82198 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to type I, II, and IV collagens.|||Expressed in heart, kidney, liver, skeletal muscle, testis, thyroid and uterus (PubMed:8024701).|||Expressed in the embryo at 12 dpc (PubMed:8024701).|||Gamma-carboxylation is controversial. Gamma-carboxyglutamated; gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation; this may be required for calcium binding. According to a more recent report, does not contain vitamin K-dependent gamma-carboxyglutamate residues.|||Plays a role in cell adhesion (PubMed:8024701). May play a role in cell-collagen interactions (By similarity).|||Secreted|||The EMI domain contains 2 expected intradomain disulfide bridges (Cys-49-Cys85 and Cys-84-Cys-97) and one unusual interdomain disulfide bridge to the second FAS1 domain (Cys-74-Cys-339). This arrangement violates the predicted disulfide bridge pattern of an EMI domain.|||extracellular matrix http://togogenome.org/gene/10090:Pycrl ^@ http://purl.uniprot.org/uniprot/Q9DCC4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pyrroline-5-carboxylate reductase family.|||Cytoplasm|||Enzyme that catalyzes the last step in proline biosynthesis. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C), and then to proline via pyrroline-5-carboxylate reductases (PYCRs). PYCRL is exclusively linked to the conversion of ornithine to proline.|||Homodecamer; composed of 5 homodimers. http://togogenome.org/gene/10090:Aida ^@ http://purl.uniprot.org/uniprot/Q8C4Q6 ^@ Function|||Similarity|||Subunit ^@ Acts as a ventralizing factor during embryogenesis (By similarity). Inhibits axin-mediated JNK activation by binding axin and disrupting axin homodimerization. This in turn antagonizes a Wnt/beta-catenin-independent dorsalization pathway activated by AXIN/JNK-signaling.|||Belongs to the AIDA family.|||Interacts with AXIN1. http://togogenome.org/gene/10090:H3c3 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Tm2d2 ^@ http://purl.uniprot.org/uniprot/Q8R0I4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TM2 family.|||Membrane http://togogenome.org/gene/10090:Acer3 ^@ http://purl.uniprot.org/uniprot/Q9D099 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by Ca(2+) and inhibited by Zn(2+).|||Belongs to the alkaline ceramidase family.|||Down-regulated in immune cells and colonic epithelial cells by lipopolysaccharides/LPS.|||Endoplasmic reticulum and Golgi ceramidase that catalyzes the hydrolysis of unsaturated long-chain C18:1-, C20:1- and C20:4-ceramides, dihydroceramides and phytoceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:26474409). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:26474409). Controls the generation of sphingosine in erythrocytes, and thereby sphingosine-1-phosphate in plasma (By similarity). Through the regulation of ceramides and sphingosine-1-phosphate homeostasis in the brain may play a role in neurons survival and function (PubMed:26474409). By regulating the levels of pro-inflammatory ceramides in immune cells and tissues, may modulate the inflammatory response (PubMed:26938296).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homozygous knockout mice are viable and do not display overt phenotype with regard to fertility, body weight and anatomy (PubMed:26474409). They exhibit a decrease in ceramidase activity in brain, liver and lung tissues leading to the age-dependent accumulation of unsaturated long-chain C18:1-ceramides and the concomitant decrease in sphingosine and sphingosine-1-phosphate (PubMed:26474409). This is associated with a premature degeneration of Purkinje cells and age-dependent defects in motor coordination, skilled hindlimb function and balance capabilities (PubMed:26474409). Knockout mice also display exacerbated systemic inflammatory response (PubMed:26938296).|||Up-regulated with age in cerebeLlum and cerebrum. http://togogenome.org/gene/10090:Gpr142 ^@ http://purl.uniprot.org/uniprot/A2AD24|||http://purl.uniprot.org/uniprot/Q1XA02|||http://purl.uniprot.org/uniprot/Q7TQN9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Orphan receptor. http://togogenome.org/gene/10090:Fcgrt ^@ http://purl.uniprot.org/uniprot/Q61559 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily.|||Cell membrane|||Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk (PubMed:7504013). IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation. In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin/ALB.|||Endosome membrane|||FcRn complex consists of two subunits: p51, and p14 which is equivalent to beta-2-microglobulin. It forms an MHC class I-like heterodimer. Interacts with albumin/ALB; this interaction regulates ALB homeostasis.|||Intestinal epithelium of suckling rodents. Expressed in neonatal intestine and fetal yolk sac. http://togogenome.org/gene/10090:Magee1 ^@ http://purl.uniprot.org/uniprot/Q6PCZ4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in cell bodies and dendrites of hippocampal and Purkinje neurons. Also expressed in peripheral nerve, where it localizes to the perineurium and myelin (at protein level). Predominantly expressed in brain and at low levels in the heart, liver, kidney, spleen, testis, lung, thymus, placenta and skeletal muscle.|||Interacts with DTNA. Interacts with TRIM28 (By similarity).|||May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex (By similarity).|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Mug1 ^@ http://purl.uniprot.org/uniprot/P28665 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A proteinase activates the inhibitor by specific proteolysis in the bait region, which, by an unknown mechanism leads to reaction at the cysteinyl-glutamyl internal thiol ester site and to a conformational change, whereby the proteinase is trapped and/or covalently bound to the inhibitor. While in the tetrameric proteinase inhibitors steric inhibition is sufficiently strong, monomeric forms need a covalent linkage between the activated glutamyl residue of the original thiol ester and a terminal amino group of a lysine or another nucleophilic group on the proteinase, for inhibition to be effective.|||Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.|||Monomer.|||Plasma.|||Secreted http://togogenome.org/gene/10090:Gldc ^@ http://purl.uniprot.org/uniprot/Q91W43 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GcvP family.|||Interacts with GCSH (By similarity). Homodimer. The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH) (By similarity).|||Mitochondrion|||Stimulated by lipoic acid. Inhibited in presence of methylamine (By similarity).|||The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH) (By similarity). http://togogenome.org/gene/10090:Reln ^@ http://purl.uniprot.org/uniprot/Q60841 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the reelin family.|||Defects in Reln are the cause of the autosomal recessive reeler (rl) phenotype which is characterized by impaired motor coordination, tremors and ataxia. Neurons in affected mice fail to reach their correct locations in the developing brain, disrupting the organization of the cerebellar and cerebral cortices and other laminated regions.|||Extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. Regulates microtubule function in neurons and neuronal migration. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation.|||First detected at embryonic day 11.5. Expression increases up to birth and remains high from postnatal day 2 to 11 in both cerebellum and fore/midbrain. Expression declines thereafter and is largely brain specific in the adult.|||N-glycosylated and to a lesser extent also O-glycosylated.|||Oligomer of disulfide-linked homodimers. Binds to the ectodomains of VLDLR and LRP8/APOER2.|||The basic C-terminal region is essential for secretion.|||The major isoform 1 is neuron-specific. It is abundantly produced during brain ontogenesis by the Cajal-Retzius cells and other pioneer neurons located in the telencephalic marginal zone and by granule cells of the external granular layer of the cerebellum. Expression is located in deeper layers in the developing hippocampus and olfactory bulb, low levels of expression are also detected in the immature striatum. At early developmental stages, expressed also in hypothalamic differentiation fields, tectum and spinal cord. A moderate to low level of expression occurs in the septal area, striatal fields, habenular nuclei, some thalamic nuclei, particularly the lateral geniculate, the retina and some nuclei of the reticular formation in the central field of the medulla. Very low levels found in liver and kidney. No expression in radial glial cells, cortical plate, Purkinje cells and inferior olivary neurons. The minor isoform 2 is only expressed in non neuronal cells. The minor isoform 3 is found in the same cells as isoform 1, but is almost undetectable in retina and brain stem.|||extracellular matrix http://togogenome.org/gene/10090:Ptprj ^@ http://purl.uniprot.org/uniprot/A2AWF8|||http://purl.uniprot.org/uniprot/A2AWF9|||http://purl.uniprot.org/uniprot/E9Q4S7|||http://purl.uniprot.org/uniprot/Q64455 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.|||Cell junction|||Cell membrane|||Expressed at 11.5 dpc in presumptive macrophages concentrated in the liver and scattered throughout the embryonic mesenchyme. Expressed at 11.5 and 12.5 dpc in the developing eye and in the ganglia and processes of cranial and spinal nerves constituting the PNS.|||Expressed at high levels in brain, kidney, spleen and intestine, and at lower levels in liver, lung, thymus and heart. Expressed at a high level in the myeloid cell line FDC-P2, and at a lower level in the pre-B lymphoid cell line WEHI-231 and the T hybridoma cell line HB21.7.31. Not expressed in the fibroblast cell line NIH3T3 or the erythroid cell line F5-5. Expressed in macrophages.|||Monomer. Interacts with CTNNB1 (phosphorylated) and JUP (phosphorylated). Interacts with FLT3 (phosphorylated). Interacts with GAB1 and GRB2 (By similarity).|||Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2 (By similarity). Plays a role in cell adhesion, migration, proliferation and differentiation (PubMed:18249142). Involved in vascular development (PubMed:12588999). May be involved in the mechanism of contact inhibition of cell growth (PubMed:12771128). Regulator of macrophage adhesion and spreading (PubMed:19268662). Positively affects cell-matrix adhesion (PubMed:12833140). Positive regulator of platelet activation and thrombosis (PubMed:19246339). Negative regulator of cell proliferation (By similarity). Negative regulator of PDGF-stimulated cell migration; through dephosphorylation of PDGFR (PubMed:12833140). Positive regulator of endothelial cell survival, as well as of VEGF-induced SRC and AKT activation; through KDR dephosphorylation (By similarity). Negative regulator of EGFR signaling pathway; through EGFR dephosphorylation (By similarity). Enhances the barrier function of epithelial junctions during reassembly (By similarity). Negatively regulates T-cell receptor (TCR) signaling (By similarity). Upon T-cell TCR activation, it is up-regulated and excluded from the immunological synapses, while upon T-cell-antigen presenting cells (APC) disengagement, it is no longer excluded and can dephosphorylate PLCG1 and LAT to down-regulate prolongation of signaling (PubMed:12913111).|||ruffle membrane http://togogenome.org/gene/10090:Tubb4a ^@ http://purl.uniprot.org/uniprot/Q9D6F9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||The highly acidic C-terminal region may bind cations such as calcium.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Or4f54 ^@ http://purl.uniprot.org/uniprot/Q8VF39 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Septin2 ^@ http://purl.uniprot.org/uniprot/E9Q3V6|||http://purl.uniprot.org/uniprot/P42208 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cleavage furrow|||Coordinated expression with SEPTIN6 and SEPTIN7.|||Cytoplasm|||Expressed at 17 dpc in the brain with levels remaining relatively stable up to adulthood (at protein level).|||Filament-forming cytoskeletal GTPase. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (By similarity). Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements (By similarity). In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes: probably acts by regulating the assembly of the tectonic-like complex (also named B9 complex) by localizing TMEM231 protein.|||Midbody|||Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules (By similarity). GTPase activity is required for filament formation (By similarity). Septin filaments are assembled from asymmetrical heterotrimers, composed of SEPTIN2, SEPTIN6 and SEPTIN7 that associate head-to-head to form a hexameric unit (By similarity). Interaction between SEPTIN2 and SEPTIN7 seems indirect (By similarity). Interacts also with SEPTIN9 and SEPTIN5 (PubMed:11739749). Interaction with SEPTIN4 not detected (PubMed:11739749). Component of a septin core octameric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 and located in the sperm annulus (By similarity). Interacts with MAP4 (By similarity). Interacts with DZIP1L (By similarity).|||Widely expressed.|||cell cortex|||cilium membrane|||cytoskeleton|||flagellum|||kinetochore|||spindle http://togogenome.org/gene/10090:Defb15 ^@ http://purl.uniprot.org/uniprot/Q8R2I5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Expressed in testis and to a lesser extent in epididymis (caput, corpus and cauda). Also weakly expressed in kidneys and colon.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Cdc27 ^@ http://purl.uniprot.org/uniprot/A2A6Q5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APC3/CDC27 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (By similarity). Interacts with RB. Interacts with FAM168B/MANI (PubMed:20716133). Interacts with MCPH1 (By similarity).|||Nucleus|||Phosphorylated. Phosphorylation on Ser-427 and Thr-447 occurs specifically during mitosis (By similarity).|||spindle http://togogenome.org/gene/10090:Tmem52 ^@ http://purl.uniprot.org/uniprot/Q9D702 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Agbl4 ^@ http://purl.uniprot.org/uniprot/E4W7Y4|||http://purl.uniprot.org/uniprot/Q09LZ8 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Golgi apparatus|||Interacts with MYLK.|||Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:21074048, PubMed:25103237, PubMed:26829768, PubMed:29593216). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein (PubMed:21074048, PubMed:25103237). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:25103237). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK (PubMed:21074048). Mediates the deglutamylation of nucleotidyltransferase CGAS, leading to CGAS antiviral defense response activation (PubMed:26829768). Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216).|||Mice are more vulnerable to DNA virus infection due to impaired immune response. Knockout mice promote somatic cell reprogramming and higher litter size at birth (PubMed:29593216). Knockout blastocytes show enhanced development (PubMed:29593216).|||Widely expressed. Expressed abundantly in testis, pituitary and brain and to a lower extent in eye, stomach, adrenal and kidney. In brain, expressed at low level in cerebellum as compared to cortex.|||centriole|||cilium basal body|||cytosol http://togogenome.org/gene/10090:Zkscan4 ^@ http://purl.uniprot.org/uniprot/Q5SZT6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Morf4l2 ^@ http://purl.uniprot.org/uniprot/Q9R0Q4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41 and VPS72/YL1. The NuA4 complex interacts with MYC and the adenovirus E1A protein. MORF4L1 may also participate in the formation of NuA4 related complexes which lack the KAT5/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. Component of the MSIN3A histone deacetylase complex, which includes SIN3A, HDAC2, ARID4B, MORF4L1, RBBP4/RbAp48, and RBBP7/RbAp46. Interacts with MRFAP1 and RB1. May also interact with one or more as yet undefined members of the TLE (transducin-like enhancer of split) family of transcriptional repressors (By similarity).|||Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also a component of the MSIN3A complex which acts to repress transcription by deacetylation of nucleosomal histones (By similarity).|||Nucleus http://togogenome.org/gene/10090:Tmem69 ^@ http://purl.uniprot.org/uniprot/Q3KQJ0 ^@ Sequence Caution|||Subcellular Location Annotation ^@ Cloning artifact.|||Membrane http://togogenome.org/gene/10090:Safb2 ^@ http://purl.uniprot.org/uniprot/Q80YR5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation (By similarity).|||Cytoplasm|||Interacts with SAFB/SAFB1 and SCAM1. Interacts with SRPK1 and inhibits its activity.|||Nucleus http://togogenome.org/gene/10090:Ang4 ^@ http://purl.uniprot.org/uniprot/Q3TMQ6|||http://purl.uniprot.org/uniprot/W0UUX7 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the pancreatic ribonuclease family.|||Detected in small intestine, caecum and colon, with the highest expression in Paneth cells in the intestinal epithelium.|||Has bactericidal activity against E.faecalis and L.monocytogenes, but not against L.innocua and E.coli. Promotes angiogenesis (in vitro). Has low ribonuclease activity (in vitro). Promotes proliferation of melanoma cells, but not of endothelial cells or fibroblasts (in vitro).|||Secreted|||Up-regulated in small intestine by contact with normal intestinal microflora. Expressed at very low levels in intestine from germ-free mice.|||nucleolus|||secretory vesicle lumen http://togogenome.org/gene/10090:Or5t16 ^@ http://purl.uniprot.org/uniprot/Q7TR59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wdr83os ^@ http://purl.uniprot.org/uniprot/Q6ZWX0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Asterix family.|||Component of the PAT complex, composed of WDR83OS/Asterix and CCDC47. The PAT complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.|||Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity). Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein. Within the PAT subcomplex, WDR83OS/Asterix binds to and redirects the substrate to a location behind the SEC61 complex (By similarity).|||Endoplasmic reticulum membrane|||Expressed in the liver. http://togogenome.org/gene/10090:Eid2 ^@ http://purl.uniprot.org/uniprot/Q6X7S9 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in heart, brain, kidney and pancreas. Not detected in placenta.|||First detected at 10.5 dpc with highest expression at 11.5 dpc. Expression decreases during later stages of development at 12.5 dpc and 14.5 dpc (at protein level).|||Heterodimer with EID2B. Interacts with the C-terminus of EP300. Interacts with HDAC1 and HDAC2. Interacts with SMAD2, SMAD4 and with the MH2 domain of SMAD3 (By similarity).|||Interacts with EP300 and acts as a repressor of MYOD-dependent transcription and muscle differentiation. Inhibits EP300 histone acetyltransferase activity. Acts as a repressor of TGFB/SMAD transcriptional responses. May act as a repressor of the TGFB/SMAD3-dependent signaling by selectively blocking formation of TGFB-induced SMAD3-SMAD4 complex (By similarity).|||Nucleus|||The N-terminal portion of EID2 is required for nuclear localization. http://togogenome.org/gene/10090:Gsk3a ^@ http://purl.uniprot.org/uniprot/Q2NL51 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit ^@ Activated by phosphorylation at Tyr-279. In response to insulin, inhibited by phosphorylation at Ser-21 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.|||Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1 (PubMed:15791206, PubMed:17908561). Requires primed phosphorylation of the majority of its substrates (PubMed:22539723). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:15791206, PubMed:17908561). Regulates glycogen metabolism in liver, but not in muscle (PubMed:17908561). May also mediate the development of insulin resistance by regulating activation of transcription factors (By similarity). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:15791206). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (By similarity). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:17391670). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (PubMed:16543145). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:22539723). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity).|||Enhanced glucose tolerance and insulin sensitivity, increased activity of hepatic glycogen synthase, elevated hepatic glycogen storage and reduced fat mass.|||Monomer. Interacts with AXIN1 and CTNNB1/beta-catenin (By similarity). Interacts with ARRB2 (PubMed:16051150). Interacts with CTNND2 (By similarity). Interacts with LMBR1L (By similarity). Interacts with DDX3X (By similarity). Interacts with TNFRSF10B (By similarity).|||Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and deactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279. http://togogenome.org/gene/10090:Mob1a ^@ http://purl.uniprot.org/uniprot/Q921Y0 ^@ Function|||PTM|||Similarity|||Subunit ^@ Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38 and STK38L. Acts cooperatively with STK3/MST2 to activate STK38 (By similarity).|||Belongs to the MOB1/phocein family.|||Binds STK38 and STK38L. Interacts with LATS1 and LATS2 (By similarity). Forms a tripartite complex with STK38 and STK3/MST2 (By similarity).|||Phosphorylated by STK3/MST2 and STK4/MST1 and this phosphorylation enhances its binding to LATS1. http://togogenome.org/gene/10090:Vmn1r171 ^@ http://purl.uniprot.org/uniprot/Q9EPS6 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Kcnc1 ^@ http://purl.uniprot.org/uniprot/P15388|||http://purl.uniprot.org/uniprot/Q3UHB6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.1/KCNC1 sub-subfamily.|||Cell membrane|||Detected in cerebellum (PubMed:11517255, PubMed:15217387). Detected in brain (at protein level) (PubMed:9037088). Detected in brain (PubMed:9037088).|||Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity). Heteromultimer with KCNC2 (By similarity). Heterotetramer with KCNC3 (By similarity). Interacts with the ancillary subunits KCNE1 and KCNE2; the interaction modulates channel activity (By similarity).|||Membrane|||Mutant mice are born at the expected Mendelian rate. They are viable and fertile, but have lower body weight than wild-type. They have normal spontaneous locomotor activity, but impaired motor skills (PubMed:9037088). Mice lacking both Kcnc3 and Kcnc1 are born at the expected Mendelian rate, but the pups do not thrive and all die about 26 days after birth when kept together with other littermates. Their failure to thrive may be due to motor problems; mutant pups survive when fed separately, but 45 days after birth their body weight is only 50 to 60 % of that of wild-type (PubMed:11517255). They appear uncoordinated and display severe ataxia, myoclonus and spontaneous whole-body muscle jerks, but display no obvious alterations in brain morphology (PubMed:11517255, PubMed:15217387, PubMed:16923152). Mutant mice are also much more sensitive to ethanol and fall sideways at ethanol concentrations that have no effect on wild-type mice (PubMed:11517255). They display increased locomotor and exploratory activity (PubMed:11517255, PubMed:15217387). Mice lacking Kcnc1 show reduced response to tremorogenic agent harmaline; mice lacking both Kcnc3 and Kcnc1 are resistant to the tremorogenic agent harmaline (PubMed:15217387).|||N-glycosylated; contains sialylated glycans.|||Presynaptic cell membrane|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||The tail may be important in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient (PubMed:2599109, PubMed:1400413). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well. Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons.|||axon http://togogenome.org/gene/10090:Rps6 ^@ http://purl.uniprot.org/uniprot/P62754|||http://purl.uniprot.org/uniprot/Q5BLK1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS6 family.|||Component of the 40S small ribosomal subunit. Plays an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Cytoplasm|||Mono-ADP-ribosylation at Glu-35 by PARP16 inhibits polysome assembly and mRNA loading, thereby inhibiting protein translation.|||Ribosomal protein S6 is the major substrate of protein kinases in eukaryote ribosomes. The phosphorylation is stimulated by growth factors, tumor promoting agents, and mitogens. It is dephosphorylated at growth arrest. Phosphorylated at Ser-235 and Ser-236 by RPS6KA1 and RPS6KA3; phosphorylation at these sites facilitates the assembly of the pre-initiation complex.|||Specifically hydroxylated (with R stereochemistry) at C-3 of Arg-137 by KDM8.|||nucleolus http://togogenome.org/gene/10090:Crem ^@ http://purl.uniprot.org/uniprot/D3YXV5|||http://purl.uniprot.org/uniprot/D3Z011|||http://purl.uniprot.org/uniprot/D3Z7M6|||http://purl.uniprot.org/uniprot/E9PV35|||http://purl.uniprot.org/uniprot/E9PWV9|||http://purl.uniprot.org/uniprot/P27699|||http://purl.uniprot.org/uniprot/Q3TTH6|||http://purl.uniprot.org/uniprot/Q9CQ87|||http://purl.uniprot.org/uniprot/Q9D599 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family.|||Binds DNA as a dimer (By similarity). Interacts with CDC34 (By similarity). Interacts with FHL5 (PubMed:10086359). May interact with TSSK4 (PubMed:26940607). Isoform 1 forms a heterodimer with CREB3L4 (PubMed:16595651).|||CREM-null deficient mice display male infertility: while spermatogonia differentiate normally into round spermatids, all the elongating spermatids are eliminated by apoptosis during spermiogenesis.|||Cytoplasm|||Expressed in the testis.|||In premeiotic germ cells, expressed at low amounts in the antagonist form. Subsequently, during spermatogenesis, isoform 1 (activator) is generated exclusively and in extremely high amounts.|||Isoform 11 is expressed in a circadian manner in the adrenal gland with an expression peak at ZT20 (at protein level). It is induced by cAMP in an immediate-early fashion and can repress its own production via a negative autoregulatory mechanism.|||Nucleus|||Plays a role in the regulation of the circadian clock: acts as a transcriptional repressor of the core circadian component PER1 by directly binding to cAMP response elements in its promoter.|||Produced by alternative promoter usage.|||Stimulated by phosphorylation (By similarity). Phosphorylated on Ser-116 by TSSK4 in vitro.|||Transcriptional regulator that binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. Isoforms are either transcriptional activators or repressors. Isoform 2, isoform 3 and isoform 4 are repressors, while isoform 1 is an activator. Plays a role in spermatogenesis and is involved in spermatid maturation. Binding of isoform 1 (activator) to CRE is increased by CREB3L4. The CREM isoform 1-CREB3L4 heterodimer functions through CRE and may recruit HIRA to CRE to regulate histone exchange (PubMed:16595651).|||Ubiquitinated by CDC34 and RAD6B in order to be degraded by the proteasome. http://togogenome.org/gene/10090:Fgf17 ^@ http://purl.uniprot.org/uniprot/P63075|||http://purl.uniprot.org/uniprot/Q0VF19 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Interacts with FGFR3 and FGFR4.|||Plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain. Required for normal brain development.|||Secreted http://togogenome.org/gene/10090:Zfp691 ^@ http://purl.uniprot.org/uniprot/Q3TDE8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Bcap31 ^@ http://purl.uniprot.org/uniprot/Q61335 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BCAP29/BCAP31 family.|||Cleaved by CASP8 and other caspases.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Functions as a chaperone protein (PubMed:9396746). Is one of the most abundant endoplasmic reticulum (ER) proteins (PubMed:9396746). Plays a role in the export of secreted proteins in the ER, the recognition of abnormally folded protein and their targeting to the ER associated-degradation (ERAD) (PubMed:9396746). Also serves as a cargo receptor for the export of transmembrane proteins (PubMed:15187134). Plays a role in the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) by stimulating the translocation of NDUFS4 and NDUFB11 from the cytosol to the mitochondria via interaction with TOMM40 (By similarity). In response to ER stress, delocalizes from the ER-mitochondria contact sites and binds BCL2 (By similarity). May be involved in CASP8-mediated apoptosis (By similarity).|||Homodimer and heterodimer with BCAP29 (PubMed:8612576). Binds CASP8 (isoform 9) as a complex containing BCAP31, BCAP29, BCL2 and/or BCL2L1 (By similarity). Forms a complex (via C-terminus) with TOMM40 which mediates the translocation of components of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) from the cytosol to the mitochondria; within the complex BCAP31 interacts directly with unprocessed and processed NDUFS4 and NDUFB11. Interacts with VDAC1 (By similarity). Interacts with VAMP3, VAMP1 and membrane IgD immunoglobulins (PubMed:9396746). Interacts with HACD2 (By similarity). Interacts with DNM1L; may form part of a larger protein complex at the endoplasmic reticulum-mitochondrial interface during mitochondrial fission (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Gcg ^@ http://purl.uniprot.org/uniprot/P55095 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glucagon family.|||Induced in response to nutrient ingestion.|||May modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.|||Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.|||Potent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6 (PubMed:22037645). Plays important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Has growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis (Probable).|||Production by pancreatic and inestinal L cells is increased by exercise in an IL6-dependent manner (PubMed:22037645). High-fat diet increases pancreatic content (PubMed:22037645).|||Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas (By similarity).|||Release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin.|||Secreted|||Secreted from enteroendocrine cells throughout the gastrointestinal tract.|||Secreted from enteroendocrine cells throughout the gastrointestinal tract. Also secreted in selected neurons in the brain.|||Secreted in the A cells of the islets of Langerhans (PubMed:22037645). Secreted from enteroendocrine L cells throughout the gastrointestinal tract (PubMed:22037645). Also secreted in selected neurons in the brain.|||Secreted in the A cells of the islets of Langerhans.|||Significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.|||Stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability. http://togogenome.org/gene/10090:Mtfr1l ^@ http://purl.uniprot.org/uniprot/Q9CWE0 ^@ Similarity ^@ Belongs to the MTFR1 family. http://togogenome.org/gene/10090:Scarb2 ^@ http://purl.uniprot.org/uniprot/O35114 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a lysosomal receptor for glucosylceramidase (GBA1) targeting.|||Acylated by palmitic acid group(s).|||Belongs to the CD36 family.|||Detected in the extracts of brain, heart, lung, liver and kidney.|||Heavily glycosylated.|||Interacts with GBA1.|||Lysosome membrane http://togogenome.org/gene/10090:Zfp239 ^@ http://purl.uniprot.org/uniprot/P24399 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus|||Preferentially expressed in transformed mouse cells. http://togogenome.org/gene/10090:Clta ^@ http://purl.uniprot.org/uniprot/B1AWD8|||http://purl.uniprot.org/uniprot/B1AWD9|||http://purl.uniprot.org/uniprot/B1AWE0|||http://purl.uniprot.org/uniprot/B1AWE1|||http://purl.uniprot.org/uniprot/Q6PFA2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the clathrin light chain family.|||Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.|||Cytoplasmic vesicle membrane|||coated pit http://togogenome.org/gene/10090:Ppp1r9a ^@ http://purl.uniprot.org/uniprot/H3BJD6|||http://purl.uniprot.org/uniprot/Q7TN74 ^@ Subcellular Location Annotation ^@ cytoskeleton http://togogenome.org/gene/10090:Alkbh8 ^@ http://purl.uniprot.org/uniprot/Q80Y20 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys) (By similarity). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:20583019). Required for normal survival after DNA damage (By similarity). May inhibit apoptosis and promote cell survival and angiogenesis (By similarity).|||Cytoplasm|||Interacts with TRMT112.|||No visible phenotype.|||Nucleus|||The Fe2OG dioxygenase domain does not have demethylase activity with methylated nucleotides. http://togogenome.org/gene/10090:Prmt6 ^@ http://purl.uniprot.org/uniprot/Q6NZB1 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA (PubMed:22904064, PubMed:26070566). Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates (By similarity). Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a (By similarity). H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3) (By similarity). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53 (PubMed:22904064). Repression of TP53 blocks cellular senescence (PubMed:22904064). Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively) (By similarity). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity (By similarity). Methylates HMGA1 (By similarity). Regulates alternative splicing events (By similarity). Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1 (By similarity). Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator (PubMed:24570487). Methylates GPS2, protecting GPS2 from ubiquitination and degradation (PubMed:26070566). Methylates SIRT7, inhibiting SIRT7 histone deacetylase activity and promoting mitochondria biogenesis (By similarity).|||Automethylation enhances its stability.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.|||Embryonic fibroblasts from mutant mice display growth defects, premature senescence and increased levels of TP53 and multiple TP53 targets. In liver, knockdown disrupts the formation of a cAMP-mediated transcription complex involving CRTC2, reduces the expression of genes encoding gluconeogenic factors and decreases glucose output in primary hepatocytes, it also restores euglycemia in insulin-resistant mice.|||Interacts with (and methylates) HIV-1 Tat, Rev and Nucleocapsid protein p7 (NC). Interacts with EPB41L3 and NCOA1.|||Nucleus http://togogenome.org/gene/10090:Gnptab ^@ http://purl.uniprot.org/uniprot/Q69ZN6 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the stealth family.|||Catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. M6P residues are required to bind to the M6P receptors (MPR), which mediate the vesicular transport of lysosomal enzymes to the endosomal/prelysosomal compartment.|||Golgi apparatus membrane|||Hexamer of two alpha, two beta and two gamma (GNPTG) subunits; disulfide-linked. The alpha and/or the beta subunits of the enzyme constitute the catalytic subunits. Interacts with LYSET; facilitates proper localization of GNPTAB.|||Severe retinal degeneration, growth retardation and secretory cell lesions. Mice are smaller with a reduced mean body weight and length, along with a reduction in total tissue mass and lean body mass. They show elevated levels of serum lysosomal enzymes, cartilage defects, and display cytoplasmic alterations in secretory cells of several exocrine glands.|||Stealth proteins are part of a protein family that is conserved from bacteria to higher eukaryotes. Family members were first identified in microbes as proteins that help pathogens to elude the host innate immune system. Microbial stealth proteins are most likely involved in the biosynthesis of exopolysaccharides. Stealth proteins are predicted to function as hexose-1-phosphoryltransferases.|||The DMAP1-binding domain mediates substrate recognition. It specifically recognizes a conformation-dependent protein determinant present in acid hydrolases.|||The alpha- and beta-subunits are generated by a proteolytic cleavage by MBTPS1 protease at the Lys-907-Asp-908 bond. http://togogenome.org/gene/10090:Spry2 ^@ http://purl.uniprot.org/uniprot/Q9QXV8 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antagonist of fibroblast growth factor (FGF) pathways via inhibition of FGF-mediated phosphorylation of ERK1/2 (PubMed:29501879). Thereby acts as an antagonist of FGF-induced retinal lens fiber differentiation, may inhibit limb bud outgrowth and may negatively modulate respiratory organogenesis (PubMed:10498682, PubMed:10074434, PubMed:29501879). Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (PubMed:25576668). Inhibits CBL/C-CBL-mediated EGFR ubiquitination (By similarity).|||At 8.5 dpc, expressed in the primitive streak, rostral forebrain, cells lateral to the posterior hindbrain, anterior hindbrain and developing midbrain. At 9.5 dpc, continues to be expressed in the rostral forebrain and primitive streak, and is also detected in the branchial arches and the forelimb bud. At 10.5 dpc, expressed in the somites, frontonasal processes, tailbud, and hindlimb bud (PubMed:10498682). Highly expressed in lung epithelial cells, primarily in the distal airways at 12 dpc (PubMed:10074434).|||Belongs to the sprouty family.|||Cleaved at Pro-143 by the prolyl endopeptidase FAP (seprase) activity (in vitro).|||Expressed in the testes and brain (at protein level) (PubMed:17974561, PubMed:10074434). In adult, highly expressed in the lung, heart and at lower levels in skeletal muscle and kidney (PubMed:10074434).|||Forms heterodimers with SPRY1 (PubMed:16877379). Forms a tripartite complex containing GAB1, METTL13 and SPRY2 (By similarity). Within the complex interacts with METTL13 (By similarity). Interacts with RAF1 (By similarity). Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction disrupts SPRY2 interaction with GRB2, potentially via disruption of SPRY2 serine dephosphorylation (PubMed:17974561). Interacts with PPP2R1A/PP2A-A and PPP2CA/PP2A-C; the interaction with PPP2CA/PP2A-C is inhibited by interaction with TESK1, possibly by vesicular sequestration of SPRY2 (By similarity). Inhibition of the interaction with the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme results in loss of PP2A-mediated dephosphorylation, resulting in the loss of SPRY2 interaction with GRB2 (By similarity). Interacts with GRB2 (By similarity). Interacts with CBL/C-CBL; the interaction inhibits CBL-mediated ubiquitination of EGFR (By similarity). Interacts (via C-terminus) with CAV1 (via C-terminus) (PubMed:16877379).|||The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.|||cytoskeleton|||ruffle membrane http://togogenome.org/gene/10090:Tpt1 ^@ http://purl.uniprot.org/uniprot/P63028 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCTP family.|||Cytoplasm|||Homodimer (By similarity). Interacts with STEAP3 (By similarity). Interacts with TSC22D1; interaction results in the destabilization of TSC22D1 protein (By similarity).|||Involved in calcium binding and microtubule stabilization (By similarity). Acts as a negative regulator of TSC22D1-mediated apoptosis, via interaction with and destabilization of TSC22D1 protein (By similarity).|||Preferentially synthesized in cells of the early growth phase of Ehrlich ascites tumor. http://togogenome.org/gene/10090:C2cd5 ^@ http://purl.uniprot.org/uniprot/Q7TPS5 ^@ Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 3 Ca(2+) ions per C2 domain.|||Cell membrane|||Cytoplasmic vesicle membrane|||Expressed in liver, muscle and fat.|||Phosphorylated on Ser-197 by active myristoylated kinase AKT2; insulin-stimulated phosphorylation by AKT2 regulates SLC2A4/GLUT4 translocation into the plasma membrane.|||Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM.|||The C2 domain binds to calcium and membrane lipids.|||cell cortex|||ruffle http://togogenome.org/gene/10090:Cacna1g ^@ http://purl.uniprot.org/uniprot/E9PWL1|||http://purl.uniprot.org/uniprot/Q5SUF6|||http://purl.uniprot.org/uniprot/Q5SUF7|||http://purl.uniprot.org/uniprot/Q5SUG0|||http://purl.uniprot.org/uniprot/Q5SUG3|||http://purl.uniprot.org/uniprot/Q5SUG4|||http://purl.uniprot.org/uniprot/Q6ZPX4|||http://purl.uniprot.org/uniprot/Q9WUT2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.|||Membrane|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. http://togogenome.org/gene/10090:Alkbh4 ^@ http://purl.uniprot.org/uniprot/Q9D8F1 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||Dioxygenase that mediates demethylation of actin monomethylated at 'Lys-84' (K84me1), thereby acting as a regulator of actomyosin-processes (By similarity). Demethylation of actin K84me1 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration (By similarity). In addition to proteins, also demethylates DNA: specifically demethylates DNA methylated on the 6th position of adenine (N(6)-methyladenosine) DNA, thereby regulating Polycomb silencing (PubMed:30982744).|||Embryonic lethality (PubMed:23673617). Conditional deletion in developing juvenile mice leads to spermatogenic defects (PubMed:25153837).|||Interacts with ZFHX3, MLLT3, MLLT1, HSF4, EP300, TES, EIF3C, MTMR6 and PSMA6.|||Midbody|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Taf4b ^@ http://purl.uniprot.org/uniprot/A0A3B2W725|||http://purl.uniprot.org/uniprot/G5E8Z2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TAF4 family.|||Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators asond repressors. TAF4B is a transcriptional coactivator of the p65/RELA NF-kappa-B subunit. Involved in the activation of a subset of antiapoptotic genes including TNFAIP3. Through interaction with OCBA/POU2AF1, acts as a coactivator of B-cell-specific transcription. Plays a role in spermiogenesis and oogenesis.|||Cytoplasm|||Deficient female mice are infertile due to a granulosa cell defect preventing normal follicle formation. Deficient male are fertile when young, but subsequently exhibit an age-dependent progressive loss of germ cells and misregulation of several genes required for normal spermatogenesis.|||Highly expressed in the testes and ovary, whereas lower levels are detected in most other tissues.|||Nucleus|||TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Heterodimerizes with TAF12/TFII20 via the C-terminal H2A-like histone-fold domain. This heterodimer forms a histone-like octamer with the TAF6/TAFII70-TAF9/TAFII31 heterodimer. Interacts with P65/RELA homodimers and P65/RELA-REL heterodimers. Interaction with POU2AF1, via its C-terminal activation domain, is required for octamer-dependent transcription (By similarity). Interacts with ZNF628 (PubMed:31932482). http://togogenome.org/gene/10090:Tapbpl ^@ http://purl.uniprot.org/uniprot/Q8VD31 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M. Association between TAPBPR and MHC class I occurs in the absence of a functional peptide-loading complex (PLC). Expression seems to slow down and down-regulate MHC class I surface expression.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Microsome membrane|||Widely expressed. http://togogenome.org/gene/10090:Zfx ^@ http://purl.uniprot.org/uniprot/B1ASD1|||http://purl.uniprot.org/uniprot/B7ZN32|||http://purl.uniprot.org/uniprot/P17012 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family. ZFX/ZFY subfamily.|||Nucleus|||Probable transcriptional activator.|||The sequence differs from that shown due to a duplication of 120 bp after position 480. http://togogenome.org/gene/10090:Klf3 ^@ http://purl.uniprot.org/uniprot/Q60980 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds to the CACCC box of erythroid cell-expressed genes. May play a role in hematopoiesis.|||In 8.5 day embryos, expressed in midbrain, anterior hindbrain and ventral forebrain. In 9 day embryos, expressed throughout ventral anterior half of embryo including midbrain-hindbrain junction, ventral midbrain, diencephalon and forebrain. At 10.5 days, distribution is more widespread with expression also found in developing limb buds. Widely expressed in the adult.|||Monomer.|||Nucleus|||Sumoylated with SUMO1. Sumoylation is enhanced by PIAS1, PIAS2alpha and PIAS2beta, and PIAS4, but not by Pc2. Enhances transcriptional repression, but has no effect on DNA binding. Sumoylation on Lys-197 is the major site.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF3, the motif is inactive. http://togogenome.org/gene/10090:Fam53a ^@ http://purl.uniprot.org/uniprot/E9PV82 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM53 family.|||May play an important role in neural development; the dorsomedial roof of the third ventricle.|||Nucleus http://togogenome.org/gene/10090:Vmn1r49 ^@ http://purl.uniprot.org/uniprot/Q9WUF1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in a subset of sensory neurons located in the apical layer of the vomeronasal organ.|||Mice show a disrupted pattern of axonal projections to the accessory olfactory bulb. Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Foxe1 ^@ http://purl.uniprot.org/uniprot/Q8R2I0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ At 13.5 dpc, it is present in endoderm derivatives, such as tongue, palate, epiglottis, pharynx, and esophagus. Later in embryogenesis, it is detected in the choanae and whiskers.|||Expressed in Rathke pouch, in thyroid, and in the epithelium of the pharyngeal wall and arches, whereas it is absent in the epithelium of the pharyngeal pouches.|||Knockout mice die before hair formation. They exhibit cleft palate and either a sublingual or completely absent thyroid gland and show neonatal hypothyroidism.|||Nucleus|||Phosphorylated.|||Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor (PubMed:21177256). Also implicated in thyroid gland morphogenesis (PubMed:9697704). May indirectly play a role in cell growth and migration through the regulation of WNT5A expression (By similarity). http://togogenome.org/gene/10090:1700029J07Rik ^@ http://purl.uniprot.org/uniprot/Q3U1D9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CFAP96 family.|||centrosome http://togogenome.org/gene/10090:Tgfbr3 ^@ http://purl.uniprot.org/uniprot/O88393 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds to TGF-beta. Could be involved in capturing and retaining TGF-beta for presentation to the signaling receptors (By similarity). In gonadotrope cells, acts as an inhibin A coreceptor and regulates follicle-stimulating hormone (FSH) levels and female fertility (PubMed:34910520, PubMed:30364975).|||Cell membrane|||Extensively modified by glycosaminoglycan (GAG), either chondroitin sulfate or heparan sulfate depending upon the tissue of origin.|||Gonadotrope-specific knockout females are supra-fertile with enhanced folliculogenesis, numbers of ovulated eggs per cycle and litter sizes relative to control mice (PubMed:30364975). Double knockout females for TGFBR3L and gonadotrope-specific TGFBR3 are infertile. They have increased serum follicle-stimulating hormone (FSH), pituitary protein content relative to controls. They have larger ovaries with increased numbers of antral follicles and corpora lutea (PubMed:34910520).|||Interacts with DYNLT4.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Slfn5 ^@ http://purl.uniprot.org/uniprot/Q8CBA2 ^@ Function|||Similarity ^@ Belongs to the Schlafen family. Subgroup III subfamily.|||May have a role in hematopoietic cell differentiation. http://togogenome.org/gene/10090:Hba-a2 ^@ http://purl.uniprot.org/uniprot/Q91VB8 ^@ Similarity ^@ Belongs to the globin family. http://togogenome.org/gene/10090:Uba52 ^@ http://purl.uniprot.org/uniprot/P62984|||http://purl.uniprot.org/uniprot/Q5M9K3 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Component of the 60S subunit of the ribosome.|||Cytoplasm|||Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.|||In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.|||In the N-terminal section; belongs to the ubiquitin family.|||Interacts with UBQLN1 (via UBA domain).|||Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.|||Nucleus|||Part of the 60S ribosomal subunit.|||Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30.|||Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. http://togogenome.org/gene/10090:Pramel31 ^@ http://purl.uniprot.org/uniprot/B1ARV5 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Nat8f6 ^@ http://purl.uniprot.org/uniprot/Q9JIY8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||Cytoplasm|||Has histone acetyltransferase activity in vitro, with specificity for histone H4.|||Nucleus membrane|||perinuclear region http://togogenome.org/gene/10090:Spata17 ^@ http://purl.uniprot.org/uniprot/Q9D552 ^@ Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||It is uncertain whether Met-1 or Met-17 is the initiator.|||Strongly expressed in adult testis but weakly expressed in the spleen and thymus. Strongly expressed in round and elongating spermatids, and weakly or not expressed in spermatozoa. http://togogenome.org/gene/10090:Bzw2 ^@ http://purl.uniprot.org/uniprot/Q91VK1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BZW family.|||Cytoplasm|||Interacts with EIF3E, EIF2S2 and EIF3C.|||Translation initiation regulator which represses non-AUG initiated translation and repeat-associated non-AUG (RAN) initiated translation by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (By similarity). Increases the accuracy of translation initiation by impeding EIF5-dependent translation from non-AUG codons by competing with it for interaction with EIF2S2 within the 43S pre-initiation complex (PIC) in an EIF3C-binding dependent manner (By similarity). http://togogenome.org/gene/10090:4930453N24Rik ^@ http://purl.uniprot.org/uniprot/Q3TTL0 ^@ Function ^@ May be involved in apoptosis regulation. http://togogenome.org/gene/10090:Gdpd2 ^@ http://purl.uniprot.org/uniprot/Q9ESM6 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Cell membrane|||Cytoplasm|||Detected in spleen, femur and calvaria.|||Has glycerophosphoinositol inositolphosphodiesterase activity and specifically hydrolyzes glycerophosphoinositol, with no activity for other substrates such as glycerophosphoinositol 4-phosphate, glycerophosphocholine, glycerophosphoethanolamine, and glycerophosphoserine. Accelerates the program of osteoblast differentiation and growth. May play a role in remodeling of the actin cytoskeleton.|||The catalytic domain of Gdpd2 is oriented extracellularly; Glycerophosphoinositol is hydrolyzed in the medium of cells overexpressing Gdpd2, whereas intracellular levels of glycerophosphoinositol is not affected.|||Up-regulated during osteoblast differentiation. Detected at low levels in mature osteoblasts.|||cytoskeleton http://togogenome.org/gene/10090:Trappc5 ^@ http://purl.uniprot.org/uniprot/Q9CQA1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAPP small subunits family. BET3 subfamily.|||Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12.|||Endoplasmic reticulum|||May play a role in vesicular transport from endoplasmic reticulum to Golgi.|||cis-Golgi network http://togogenome.org/gene/10090:Ccdc39 ^@ http://purl.uniprot.org/uniprot/Q3TQ36|||http://purl.uniprot.org/uniprot/Q9D5Y1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CCDC39 family.|||Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella. Probably acts together with CCDC40 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella. Not required for outer dynein arm complexes assembly.|||Strongly expressed in tissues rich in ciliated cells. Expressed in olfactory and vomeronasal sensory neurons and the respiratory epithelium. Expressed in node cells carrying motile cilia, in upper and lower airways, and in ependymal and choroid plexus cells.|||cilium axoneme http://togogenome.org/gene/10090:Vmn1r249 ^@ http://purl.uniprot.org/uniprot/K9J7F4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Synj1 ^@ http://purl.uniprot.org/uniprot/D3Z656|||http://purl.uniprot.org/uniprot/E9Q7S0 ^@ Similarity ^@ Belongs to the synaptojanin family.|||In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family. http://togogenome.org/gene/10090:Ildr1 ^@ http://purl.uniprot.org/uniprot/Q8CBR1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. LISCH7 family.|||Cell membrane|||Cytoplasm|||Expressed early in development.|||Expressed in the vestibule and in hair cells and supporting cells of the cochlea. Expressed in epithelial tissues. Highly expressed in colon but also detected in small intestine, bladder and lung (PubMed:23239027). In colon, expressed in the upper portion of the crypts (at protein level) (PubMed:23239027). Expressed in CCK secretory cells of the proximal small intestine (at protein level) (PubMed:23863714). Expressed in the organ of Corti, stria vascularis, utricle and saccule of the inner ear (PubMed:23239027, PubMed:25217574).|||Homooligomer (By similarity). Interacts with MARVELD2 and OCLN; the interaction is required to recruit MARVELD2 to tricellular contacts (PubMed:23239027). Interacts (via C-terminus) with TRA2A, TRA2B and SRSF1 (PubMed:28785060). Interacts with PLSCR1 (By similarity).|||Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (tTJs) (PubMed:23239027). Crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs (PubMed:25217574). Mediates fatty acids and lipoproteins-stimulated CCK/cholecystokinin secretion in the small intestine (PubMed:23863714). In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1 (PubMed:28785060).|||Mutant mice have early-onset severe deafness associated with a rapid degeneration of cochlear hair cells but have a normal endocochlear potential (PubMed:25217574). Mutants show no increase in plasma CCK levels after orogastric gavage with fatty acids (PubMed:23863714).|||Nucleus|||tight junction http://togogenome.org/gene/10090:B4galt4 ^@ http://purl.uniprot.org/uniprot/Q9JJ04 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 7 family.|||Galactose (Gal) transferase involved in the synthesis of terminal N-acetyllactosamine (LacNac) unit present on glycan chains of glycoproteins and glycosphingolipids. Catalyzes the transfer of Gal residue via a beta1->4 linkage from UDP-Gal to the non-reducing terminal N-acetyl glucosamine 6-O-sulfate (6-O-sulfoGlcNAc) in the linearly growing chain of both N- and O-linked keratan sulfate proteoglycans. Cooperates with B3GNT7 N-acetyl glucosamine transferase and CHST6 and CHST1 sulfotransferases to construct and elongate mono-and disulfated disaccharide units [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] and [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Transfers Gal residue via a beta1->4 linkage to terminal 6-O-sulfoGlcNAc within the LacNac unit of core 2 O-glycans forming 6-sulfo-sialyl-Lewis X (sLex). May contribute to the generation of sLex epitope on mucin-type glycoproteins that serve as ligands for SELL/L-selectin, a major regulator of leukocyte migration. In the biosynthesis pathway of neolacto-series glycosphingolipids, transfers Gal residue via a beta1->4 linkage to terminal GlcNAc of a lactotriaosylceramide (Lc3Cer) acceptor to form a neolactotetraosylceramide.|||Golgi apparatus membrane|||Interacts with SLC35A2/UGT1.|||Secreted http://togogenome.org/gene/10090:Cmklr2 ^@ http://purl.uniprot.org/uniprot/Q8K087 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the chemokine-like receptor (CMKLR) family.|||Cell membrane|||Deficient mice have normal body weight, adipose development, and tissue inflammation under physiologic conditions. However, when fed on a high-fat diet, Cmklr2 knockout mice develop heightened glucose intolerance, compared with WT, with no effect on body weight, percent body fat, or energy expenditure due to consumption of significantly less food. Moreover, mice lacking Cmklr2 exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test.|||High expressed in white adipose tissue and skeletal muscle (PubMed:24895415). Expressed in hippocampus and cortex (PubMed:29799787).|||Receptor for chemoattractant adipokine chemerin/RARRES2 suggesting a role for this receptor in the regulation of inflammation and energy homesotasis (PubMed:24895415). Signals mainly via beta-arrestin pathway. Binding of RARRES2 activates weakly G proteins, calcium mobilization and MAPK1/MAPK3 (ERK1/2) phosphorylation too. Acts also as a receptor for TAFA1, mediates its effects on neuronal stem-cell proliferation and differentiation via the activation of ROCK/ERK and ROCK/STAT3 signaling pathway (PubMed:29799787). http://togogenome.org/gene/10090:Matn1 ^@ http://purl.uniprot.org/uniprot/P51942 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cartilage matrix protein is a major component of the extracellular matrix of non-articular cartilage. It binds to collagen.|||Homotrimer. Interacts with COMP (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Bfar ^@ http://purl.uniprot.org/uniprot/Q8R079 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Apoptosis regulator. Has anti-apoptotic activity, both for apoptosis triggered via death-receptors and via mitochondrial factors (By similarity).|||Endoplasmic reticulum membrane|||Interacts with CASP8, BCL2 and BCL2L1 through SAM domain and also with HIP1, IFT57, ESRRBL1 and BCAP31. http://togogenome.org/gene/10090:Stxbp3 ^@ http://purl.uniprot.org/uniprot/Q60770 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Cell membrane|||Interacts with STX4. Interacts with DOC2B; the interaction is direct, occurs at the cell membrane, excludes interaction with STX4 and regulates glucose-stimulated insulin secretion.|||Phosphorylated by PKC in platelets in response to thrombin stimulation; phosphorylation inhibits binding to STX4.|||Together with STX4 and VAMP2, may play a role in insulin-dependent movement of GLUT4 and in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes.|||Ubiquitously expressed in all tissues tested.|||cytosol http://togogenome.org/gene/10090:Vmn1r26 ^@ http://purl.uniprot.org/uniprot/Q8R2D7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gdf11 ^@ http://purl.uniprot.org/uniprot/Q9Z1W4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Deficient mice die neonatally showing altered patterning of the axial skeleton and impaired renal, palate, stomach, spleen and pancreatic development.|||First strongly expressed in restricted domains at 8.5 dpc where it is highest in the tail bud. At 10.5 dpc, expressed in the branchial arches, limb bud, tail bud and posterior dorsal neural tube. Later, expressed in terminally-differentiated odontoblasts, the nasal epithelium, retina and specific regions of the brain.|||Highly expressed in the developing limb bud, initially detected in the distal mesenchyme, and later localizing to regions around the developing bones. Is also expressed in adult dental pulp and brain.|||Homodimer; disulfide-linked (By similarity). Interacts directly with ACVR2B (PubMed:16845371, PubMed:12414726). Interacts directly with ACVR2A (PubMed:12414726). Interacts with ACVR1B, TGFBR1 and ACVR1C in an ACVR2B-dependent manner (PubMed:16845371). Interacts with FST isoform 2/FS288 (By similarity).|||Secreted|||Secreted signal that acts globally to regulate anterior/posterior axial patterning during development (PubMed:10391213). May play critical roles in patterning both mesodermal and neural tissues (PubMed:10391213). It is required for proper vertebral patterning and orofacial development (By similarity). Signals through activin receptors type-2, ACVR2A and ACVR2B, and activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the phosphorylation of SMAD2 and SMAD3 (PubMed:16845371, PubMed:12414726).|||Synthesized as large precursor molecule that undergoes proteolytic cleavage by furin-like proteases (By similarity). This produces an inactive form consisting of the mature C-terminal portion non-covalently bound to its cleaved N-terminal propeptide. Activation of the mature form requires additional cleavage of the propeptide by a tolloid-like metalloproteinase. http://togogenome.org/gene/10090:Gpn3 ^@ http://purl.uniprot.org/uniprot/Q9D3W4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the GPN-loop GTPase family.|||Heterodimer with GPN1. Binds to RNA polymerase II (RNAPII). Interacts directly with subunits RPB4 and RPB7 and the CTD of RPB1.|||Small GTPase required for proper localization of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import. http://togogenome.org/gene/10090:Haao ^@ http://purl.uniprot.org/uniprot/Q78JT3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 3-HAO family.|||Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.|||Monomer.|||No visible phenotype. Mice were born at the expected Mendelian ratio and are normal. They however show very high levels of 3-hydroxyanthranilate compared to wild-type mice.|||cytosol http://togogenome.org/gene/10090:Trhde ^@ http://purl.uniprot.org/uniprot/Q8BZN0|||http://purl.uniprot.org/uniprot/Q8K093 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Homodimer; disulfide-linked.|||Membrane|||Specific inactivation of TRH after its release. http://togogenome.org/gene/10090:Or5k17 ^@ http://purl.uniprot.org/uniprot/Q8VGQ7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Gsap ^@ http://purl.uniprot.org/uniprot/Q3TCV3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GSAP family.|||Interacts with APP; specifically interacts with the CTF-alpha product of APP. Interacts with the gamma-secretase complex (By similarity).|||Regulator of gamma-secretase activity, which specifically activates the production of amyloid-beta protein (amyloid-beta protein 40 and amyloid-beta protein 42), without affecting the cleavage of other gamma-secretase targets such has Notch. The gamma-secretase complex is an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Specifically promotes the gamma-cleavage of APP CTF-alpha (also named APP-CTF) by the gamma-secretase complex to generate amyloid-beta, while it reduces the epsilon-cleavage of APP CTF-alpha, leading to a low production of AICD.|||The protein is first synthesized as a holoprotein form of 98 kDa and rapidly processed into the gamma-secretase-activating protein 16 kDa C-terminal form, which constitutes the predominant form.|||trans-Golgi network http://togogenome.org/gene/10090:Wwox ^@ http://purl.uniprot.org/uniprot/Q91WL8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||By hyaluronidase. Up-regulated in outer and inner nuclear layers during retinal degeneration.|||Cytoplasm|||Expression starts at 8 dpc in the developing heart. Higher expression in the brain is detected between 12 dpc and 16 dpc. High levels of expression in dorsal root ganglia and spinal nerves were observed throughout all developmental stages. In later developmental stages expression is more prominent in skeletal systems (at protein level).|||Golgi apparatus|||Indistinguishable from wild-type at birth, but die after three weeks due to metabolic syndrome characterized by serum hypoproteinemia, hypoalbuminemia, hypoglycemia, hypocalcemia, hypotriglyceridemia and hypocholesterolemia, growth retardation, decreased bone formation and increased bone resorption. In addition, spontaneous tumor development was observed.|||Interacts with TP53, p73/TP73 and MAPK8 (PubMed:11058590, PubMed:12514174). Interacts with MAPT/TAU, RUNX2 and HYAL2 (PubMed:15126504, PubMed:16219768) (By similarity). Forms a ternary complex with TP53 and MDM2 (By similarity). Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207 (By similarity). Interacts (via WW domain) with VOPP1 (By similarity).|||Lysosome|||Mitochondrion|||Nucleus|||Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation (By similarity).|||Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm (By similarity). May also play a role in tumor necrosis factor (TNF)-mediated cell death. Required for normal bone development.|||The WW 1 domain mediates interaction with TP73, TFAP2C, LITAF, WBP1 and probably TP53.|||Ubiquitinated when phosphorylated by TNK2, leading to its degradation.|||Ubiquitous. In the brain, expressed in cortex, striatum, hippocampus and cerebellum (at protein level). Detected in embryonic skeleton, in cranofacial bones, vertebrae and limb bones. Detected in chondrocytes and osteoblasts. http://togogenome.org/gene/10090:Fam25a ^@ http://purl.uniprot.org/uniprot/Q8CF02 ^@ Similarity ^@ Belongs to the FAM25 family. http://togogenome.org/gene/10090:Tmem255b ^@ http://purl.uniprot.org/uniprot/G3UWB7|||http://purl.uniprot.org/uniprot/G5E908|||http://purl.uniprot.org/uniprot/Q5FW56 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM255 family.|||Membrane http://togogenome.org/gene/10090:Nkx2-2 ^@ http://purl.uniprot.org/uniprot/P42586|||http://purl.uniprot.org/uniprot/Q3URZ4|||http://purl.uniprot.org/uniprot/Q8BRS9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NK-2 homeobox family.|||Expressed during embryogenesis.|||Expressed in restricted areas of the developing CNS: the hindbrain and forebrain, and pancreas.|||Interacts with OLIG2.|||Mutant embryos do not form any insulin-expressing cells in the pancreas throughout development, and instead accumulate incompletely differentiated beta cells (PubMed:11076772). Simultaneous knockout of NKX6-1 and NKX2-2 is not distinguable from the single NKX2-2 knockout (PubMed:11076772).|||Nucleus|||The homeodomain is essential for interaction with OLIG2.|||Transcriptional activator involved in the development of insulin-producting beta cells in the endocrine pancreas (PubMed:11076772). May also be involved in specifying diencephalic neuromeric boundaries, and in controlling the expression of genes that play a role in axonal guidance. Binds to elements within the NEUROD1 promoter (PubMed:19759004). http://togogenome.org/gene/10090:Marcksl1 ^@ http://purl.uniprot.org/uniprot/P28667 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MARCKS family.|||Binds to filamentous actin (F-actin), but not to monomeric G-actin, independently of its phosphorylation status (PubMed:22751924). Interacts with calmodulin (PubMed:1618855).|||Cell membrane|||Expressed at high levels in brain cortex and hippocampus, including dentate gyrus, anterior olfactory nucleus, primary olfactory cortex, entorhinal cortex, medial preoptic area and dorsomedial hypothalamic nucleus (at protein level) (PubMed:1864362, PubMed:8406449, PubMed:9598313, PubMed:22751924). Expressed in neuronal cells (at protein level) (PubMed:22751924). Detected in the retina (PubMed:9598313). Strongly expressed in testis and uterus; expressed at lower levels in cerebellum, cerebrum, adipose tissue, spleen, kidney, thyroid, liver, lung, skeletal muscle and heart (PubMed:8406449). Detected in T-cells and B-cells (PubMed:8406449).|||Expressed in the developing neural tube as early as 8.5 dpc. Remains most highly expressed in the developing brain and spinal cord during later development at least until 14.5 dpc. Also detected in the lung, adrenal gland, gut and kidney, particularly the kidney cortex. Undetectable in the liver.|||Involved in the control of cell movement by regulating actin cytoskeleton homeostasis and filopodium and lamellipodium formation (PubMed:22751924). When unphosphorylated, induces cell migration (PubMed:22751924). When phosphorylated by MAPK8, induces actin bundles formation and stabilization, thereby reducing actin plasticity, hence restricting cell movement, including neuronal migration (PubMed:22751924). May be involved in coupling the protein kinase C and calmodulin signal transduction systems (Probable).|||Phosphorylated (PubMed:1618855, PubMed:22751924). Phosphorylation at Ser-120 and Thr-183 is non-redundantly catalyzed by MAPK8 in vivo (PubMed:22751924). Phosphorylation at Thr-148 is preferentially catalyzed by MAPK8 in vivo, but this modification can also be catalyzed by other kinases in the absence of MAPK8 (PubMed:22751924). May be phosphorylated by protein kinase C, which disrupts the interaction with calmodulin (PubMed:1618855).|||Up-regulated in peritoneal macrophages in response to bacterial lipopolysaccharide (LPS).|||cytoskeleton http://togogenome.org/gene/10090:Tshr ^@ http://purl.uniprot.org/uniprot/P47750 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.|||Cell membrane|||Defects in Tshr are the cause of hyt/hyt hypothyroidism, an autosomal recessive, fetal-onset, severe hypothyroidism related to TSH hyporesponsiveness and associated with elevated TSH.|||Glycosylated.|||Interacts with heterodimer GPHA2:GPHB5; this interaction stimulates cAMP production. Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function.|||Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Plays a central role in controlling thyroid cell metabolism.|||Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin receptor binding and activation. http://togogenome.org/gene/10090:Rab42 ^@ http://purl.uniprot.org/uniprot/Q0PD08 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Membrane http://togogenome.org/gene/10090:Hepacam2 ^@ http://purl.uniprot.org/uniprot/Q4VAH7 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Golgi apparatus membrane|||Midbody|||N-glycosylated.|||Poly-ADP-ribosylated (PARsylated) by tankyrase TNKS during late G2 and prophase, leading to translocation to mitotic centrosomes.|||Required during prometaphase for centrosome maturation. Following poly-ADP-ribosylation (PARsylation) by TNKS, translocates from the Golgi apparatus to mitotic centrosomes and plays a key role in the formation of robust microtubules for prompt movement of chromosomes: anchors AKAP9/CG-NAP, a scaffold protein of the gamma-tubulin ring complex and promotes centrosome maturation (By similarity).|||centrosome|||spindle http://togogenome.org/gene/10090:Txnl1 ^@ http://purl.uniprot.org/uniprot/Q8CDN6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Active thioredoxin with a redox potential of about -250 mV.|||Component of the 19S regulatory cap of the 26S proteasome. Interacts with PSMD14/RPN11. Interacts with, and reduces EEF1A1 (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Or1e19 ^@ http://purl.uniprot.org/uniprot/Q8VGT2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mmachc ^@ http://purl.uniprot.org/uniprot/Q9CZD0 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MMACHC family.|||Can utilize both FAD and FMN.|||Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate. Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle. Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine. Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether. The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors. Cysteine and homocysteine cannot substitute for glutathione in this reaction.|||Complete embryonic lethality. All die before 3.5 dpc.|||Detected in liver and kidney (at protein level) (PubMed:21697092). Detected in embryos (PubMed:24889031).|||Monomer in the absence of bound substrate. Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin. Interacts with LMBRD1 and ABCD4; the interaction ensures the transport of cobalamin from the lysosome to the cytoplasm. Forms a multiprotein complex with MMADHC, MTR and MTRR; the interaction with MTR could modulate MMACHC-dependent processing of cobalamin. Heterodimer with MMADHC; the interaction might play a role in the regulation of the balance between AdoCbl and MeCbl synthesis.|||cytosol http://togogenome.org/gene/10090:Fem1b ^@ http://purl.uniprot.org/uniprot/Q9Z2G0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abnormal glucose tolerance predominantly due to defective glucose-stimulated insulin secretion (PubMed:16024793). Mice also show defects in prostate ductal morphogenesis and secretory protein expression (PubMed:18816836).|||Activity of the CRL2(FEM1B) complex toward FNIP1 is inhibited by BEX family proteins (BEX1, BEX2, BEX3 and/or BEX4) in absence of reductive stress (PubMed:34562363). Mechanistically, BEX proteins act as pseudosubstrate inhibitors that associate with FEM1B via zinc in absence of reductive stress, thereby preventing association between FEM1B and FNIP1 (PubMed:34562363).|||Belongs to the fem-1 family.|||Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1B (PubMed:32941802). Homooligomer (By similarity). Interacts with PPM1F and PHTF1 (PubMed:15601915). Interacts with the death domain of FAS/TNFRSF6 and TNFRSF1A. Interacts with CHEK1 (By similarity). Interacts with NKX3-1 (PubMed:18816836).|||Cytoplasm|||Expressed in pancreatic islets, within both beta cells and non-beta cells (at protein level) (PubMed:16024793). Highly expressed in adult testis; expressed in all types of spermatogonia (PubMed:9828124, PubMed:18816836). Also expressed in the prostate of neonatal mice (PubMed:18816836).|||Nucleus|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (By similarity). The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, such as CDK5R1, leading to their ubiquitination and degradation (By similarity). Also acts as a regulator of the reductive stress response by mediating ubiquitination of reduced FNIP1: in response to reductive stress, the CRL2(FEM1B) complex specifically recognizes a conserved Cys degron in FNIP1 when this degron is reduced, leading to FNIP1 degradation and subsequent activation of mitochondria to recalibrate reactive oxygen species (ROS) (PubMed:32941802, PubMed:34562363). Mechanistically, recognizes and binds reduced FNIP1 through two interface zinc ions, which act as a molecular glue that recruit reduced FNIP1 to FEM1B (PubMed:34562363). Promotes ubiquitination of GLI1, suppressing GLI1 transcriptional activator activity (By similarity). Promotes ubiquitination and degradation of ANKRD37 (PubMed:21723927). Promotes ubiquitination and degradation of SLBP (By similarity). Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis (By similarity). Also involved in glucose homeostasis in pancreatic islet (PubMed:16024793). May also act as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1 (By similarity). http://togogenome.org/gene/10090:Or5ac20 ^@ http://purl.uniprot.org/uniprot/Q8VGQ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hpse2 ^@ http://purl.uniprot.org/uniprot/B2RY83 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 79 family.|||Binds heparin and heparan sulfate with high affinity, but lacks heparanase activity. Inhibits HPSE, possibly by competing for its substrates (in vitro) (By similarity).|||Interacts with HPSE. Interacts with SDC1 (via glycan chains) (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Or5m8 ^@ http://purl.uniprot.org/uniprot/Q7TR87 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rgr ^@ http://purl.uniprot.org/uniprot/Q543X1|||http://purl.uniprot.org/uniprot/Q9Z2B3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Covalently binds all-trans- and 11-cis-retinal.|||Membrane|||Receptor for all-trans- and 11-cis-retinal. Binds preferentially to the former and may catalyze the isomerization of the chromophore by a retinochrome-like mechanism (By similarity). http://togogenome.org/gene/10090:Cacnb2 ^@ http://purl.uniprot.org/uniprot/C7IVS7|||http://purl.uniprot.org/uniprot/Q32MF3|||http://purl.uniprot.org/uniprot/Q8CC27 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calcium channel beta subunit family.|||Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (PubMed:14674701, PubMed:36424916). Plays a role in shifting voltage dependencies of activation and inactivation of the channel (By similarity). May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (PubMed:36424916). Involved in membrane targeting of the alpha-1 subunit CACNA1C (By similarity).|||Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (By similarity). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). Interacts with CACNA1C (By similarity). Interacts with RRAD; interaction may be involved in beta-adrenergic regulation of heart rate and contractile force (PubMed:36424916). Interaction with RRAD regulates the trafficking of CACNA1C to the cell membrane (By similarity). Interacts with TMIGD2 (By similarity). Interacts with CAMK2D (By similarity). Interacts with CBARP (PubMed:24751537). Interacts with CAMK2A (By similarity).|||Regulated through phosphorylation at Thr-549 by CaMK2D.|||sarcolemma http://togogenome.org/gene/10090:Tlnrd1 ^@ http://purl.uniprot.org/uniprot/Q9ERE8 ^@ Function|||Subunit|||Tissue Specificity ^@ Actin-binding protein which may have an oncogenic function and regulates cell proliferation, migration and invasion in cancer cells.|||May homodimerize. Interacts with F-actin.|||Ubiquitous. http://togogenome.org/gene/10090:Spata5l1 ^@ http://purl.uniprot.org/uniprot/A0A7N9VSG0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent chaperone, which plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Acts together with AFG2A, AIRIM and CINP.|||Associates with pre-60S ribosomal particles. Interacts with AIRIM.|||Belongs to the AAA ATPase family. AFG2 subfamily.|||Cytoplasm|||In adult ear, expressed at low levels in neurosensory hair cells (inner and outer) and supporting cells (pillar and Deiter cells).|||Nucleus|||spindle http://togogenome.org/gene/10090:Tsr1 ^@ http://purl.uniprot.org/uniprot/Q5SWD9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Bms1-like GTPase family. TSR1 subfamily.|||Required during maturation of the 40S ribosomal subunit in the nucleolus.|||nucleolus http://togogenome.org/gene/10090:Dnai1 ^@ http://purl.uniprot.org/uniprot/Q8C0M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynein intermediate chain family.|||Consists of at least two heavy chains and a number of intermediate and light chains. Interacts with BICD2 (By similarity). Interacts with CFAP45 and CFAP52 (By similarity).|||Part of the dynein complex of respiratory cilia.|||cilium axoneme http://togogenome.org/gene/10090:Mrps16 ^@ http://purl.uniprot.org/uniprot/Q9CPX7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS16 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ereg ^@ http://purl.uniprot.org/uniprot/Q61521 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Expressed in 7-day-old embryos with levels then falling to very low or undetectable amounts. Not detected in adult.|||Interacts with EGFR and ERBB4.|||Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation (By similarity). Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation (PubMed:24631357).|||extracellular space http://togogenome.org/gene/10090:Vmn2r14 ^@ http://purl.uniprot.org/uniprot/E9Q759 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Fdft1 ^@ http://purl.uniprot.org/uniprot/P53798 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the phytoene/squalene synthase family.|||Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene (PubMed:10521476). Proceeds in two distinct steps. In the first half-reaction, two molecules of FPP react to form the stable presqualene diphosphate intermediate (PSQPP), with concomitant release of a proton and a molecule of inorganic diphosphate. In the second half-reaction, PSQPP undergoes heterolysis, isomerization, and reduction with NADPH or NADH to form squalene. It is the first committed enzyme of the sterol biosynthesis pathway (By similarity).|||Deficient mice are embryonic lethal around midgestation (9.5-10.5 dpc). Embryos exhibit severe growth retardation and defective neural tube closure.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Rrp15 ^@ http://purl.uniprot.org/uniprot/Q9CYX7 ^@ PTM|||Similarity ^@ Belongs to the RRP15 family.|||Citrullinated by PADI4. http://togogenome.org/gene/10090:Zfp120 ^@ http://purl.uniprot.org/uniprot/Q8BZW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus|||Widely expressed with highest levels in kidney, brain, and liver, and the lowest levels in spleen. http://togogenome.org/gene/10090:Ndufa13 ^@ http://purl.uniprot.org/uniprot/Q9ERS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This apoptotic activity is inhibited by interaction with viral IRF1. Prevents the transactivation of STAT3 target genes. May play a role in CARD15-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes.|||Belongs to the complex I NDUFA13 subunit family.|||Complex I is composed of 45 different subunits. Interacts with CARD15, but not with CARD4. Interacts with STAT3, but not with STAT1, STAT2 and STAT5A. Interacts with OLFM4.|||Mitochondrion inner membrane|||Nucleus http://togogenome.org/gene/10090:Parl ^@ http://purl.uniprot.org/uniprot/Q5XJY4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S54 family.|||Interacts with PSEN1 and PSEN2 (By similarity). Binds OPA1.|||Mice develop normally until 4 weeks of age. They show subsequent progressive growth retardation, atrophy of muscle, spleen, and thymus as well as severe apoptosis of T and B lymphocytes leading to premature death between 8-12 weeks of age. Mouse embryonic fibroblasts lacking Parl show high susceptibility to intrinsic apoptotic signals. This defect can be complemented by Parl or a soluble form of Opa1.|||Mitochondrion inner membrane|||Nucleus|||P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner.|||Required for the control of apoptosis during postnatal growth (PubMed:16839884). Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (PubMed:16839884). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (By similarity). Promotes cleavage of serine/threonine-protein phosphatase PGAM5 in damaged mitochondria in response to loss of mitochondrial membrane potential (By similarity). Mediates differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria, disassociating from PINK1 and associating with PGAM5 in response to mitochondrial membrane potential loss (By similarity). Required for processing of CLPB into a form with higher protein disaggregase activity by removing an autoinhibitory N-terminal peptide (By similarity). Promotes processing of DIABLO/SMAC in the mitochondrion which is required for DIABLO apoptotic activity (By similarity). Also required for cleavage of STARD7 and TTC19 (By similarity). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (By similarity). http://togogenome.org/gene/10090:Strip1 ^@ http://purl.uniprot.org/uniprot/Q3UGC1|||http://purl.uniprot.org/uniprot/Q8C079 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STRIP family.|||Component of striatin-interacting phosphatase and kinase (STRIPAK) complex (PubMed:18782753). Interacts with CDC42BPB. Interacts with CTTNBP2NL.|||Cytoplasm|||Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape (By similarity). http://togogenome.org/gene/10090:Ptms ^@ http://purl.uniprot.org/uniprot/Q9D0J8 ^@ Function|||Similarity ^@ Belongs to the pro/parathymosin family.|||Parathymosin may mediate immune function by blocking the effect of prothymosin alpha which confers resistance to certain opportunistic infections. http://togogenome.org/gene/10090:Slc35g1 ^@ http://purl.uniprot.org/uniprot/Q8BY79 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM20 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with STIM1; stimulated by depletion of intracellular calcium. Interacts with ORAI1. Interacts with the plasma membrane calcium-transporting ATPases ATP2B1 and ATP2B4. Interacts with ATP1A1, ATP2A2, KPNB1 and XPO1 (By similarity).|||May play a role in intracellular calcium sensing and homeostasis. May act as a negative regulator of plasma membrane calcium-transporting ATPases preventing calcium efflux from the cell (By similarity). http://togogenome.org/gene/10090:Dhrs1 ^@ http://purl.uniprot.org/uniprot/Q99L04 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum|||May be attached to the ER membrane by its C-terminus segment.|||NADPH-dependent oxidoreductase which catalyzes the reduction of some steroids (estrone, androstene-3,17-dione and cortisone) as well as prostaglandin E1, isatin and xenobiotics in vitro. May have a role in steroid and/or xenobiotic metabolism. http://togogenome.org/gene/10090:Tas2r121 ^@ http://purl.uniprot.org/uniprot/Q7M720 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Cell membrane|||Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.|||Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity). http://togogenome.org/gene/10090:Mthfd2 ^@ http://purl.uniprot.org/uniprot/P18155 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency.|||Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.|||Homodimer.|||Mitochondrion|||This NAD-dependent bifunctional enzyme has very different kinetic properties than the larger NADP-dependent trifunctional enzyme and is unique in that it requires formation of an enzyme-magnesium complex to allow binding of NAD. http://togogenome.org/gene/10090:Phactr4 ^@ http://purl.uniprot.org/uniprot/Q501J7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphatase and actin regulator family.|||Binds PPP1CA and actin.|||Cytoplasm|||During embryonic development, most strongly expressed in neural tissue. Expressed in a dynamic pattern during neurulation: from 8.5 dpc to 9.5 dpc, the period of cranial neural closure and spatially regulated proliferation, it is expressed strongly in the ventral region of the cranial neural tube. By 10.5 dpc, expressed more uniformly along the dorsal and ventral aspects of the cranial neural tube. Also expressed in the neural retina and lens.|||Neural tube and eye defects in embryos followed by death. By 9.25 dpc, mutant embryos show failure to close the cranial neural tube. About 15% of homozygous mutant embryos exhibit severe exencephaly, along with a wavy spinal neural tube and a shortened anterior/posterior body axis, and die around 10.5 dpc. Remaining embryos exhibit complete exencephaly from the forebrain to hindbrain. Most embryos die by 14.5 dpc, but a few survive to birth and die shortly thereafter. Embryos also have eye defects: they display overgrowth of the neural retina and retinal pigment epithelium. Embryos also display coloboma at 12.5 dpc and 16.5 dpc, due to defects in closure of optic fissure. Defects are due to elevated proliferation and abnormally phosphorylated, inactive PP1, resulting in RB1 hyperphosphorylation, derepression of E2F targets, and abnormal cell-cycle progression. Embryos also show embryonic gastrointestinal defects due to colon hypoganglionosis, which resembles human Hirschsprung disease: ENCCs within the embryonic gut display a collective cell migration defect and show undirected cellular protrusions and disrupted directional and chain migration.|||Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway.|||lamellipodium http://togogenome.org/gene/10090:P2ry12 ^@ http://purl.uniprot.org/uniprot/Q546L4|||http://purl.uniprot.org/uniprot/Q9CPV9 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice are viable and fertile, but display impaired blood coagulation, due to defects in platelet aggregation and thrombus formation.|||Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Required for normal platelet aggregation and blood coagulation.|||The transmembrane domain is composed of seven transmembrane helices; most of these are not strictly perpendicular to the plane of the membrane, but are tilted and/or kinked. Agonist binding promotes a conformation change in the extracellular loops that leads to an inward movement of the transmembrane helices. Antagonists can bind to an overlapping site, but block the inward movement of the transmembrane helices (By similarity). http://togogenome.org/gene/10090:Il5 ^@ http://purl.uniprot.org/uniprot/P04401|||http://purl.uniprot.org/uniprot/Q5SV01 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-5 family.|||Homodimer; disulfide-linked.|||Homodimer; disulfide-linked. Interacts with IL5RA (PubMed:1873482). Interacts with CSF2RB.|||Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:10444455, PubMed:1873482). Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation (PubMed:3128631). Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB. Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively (By similarity).|||Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils. Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation. Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB. Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively.|||In IL-5 deletion mice, the intestinal eosinophilia that developed in WT mice during T. spiralis infection was completely abolished, revealing the importance of IL5 for the increased production and recruitment of eosinophils to the gut during infection.|||Secreted http://togogenome.org/gene/10090:Lgals8 ^@ http://purl.uniprot.org/uniprot/Q9JL15 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Beta-galactoside-binding lectin that acts as a sensor of membrane damage caused by infection and restricts the proliferation of infecting pathogens by targeting them for autophagy. Detects membrane rupture by binding beta-galactoside ligands located on the lumenal side of the endosome membrane; these ligands becoming exposed to the cytoplasm following rupture. Restricts infection by initiating autophagy via interaction with CALCOCO2/NDP52. Required to restrict infection of bacterial invasion such as S.typhimurium. Also required to restrict infection of Picornaviridae viruses. Has a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans.|||Contains two homologous but distinct carbohydrate-binding domains.|||Cytoplasmic vesicle|||Homodimer. Interacts with CALCOCO2/NDP52. Interacts with PDPN; the interaction is glycosylation-dependent; may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix.|||cytosol http://togogenome.org/gene/10090:Acss2 ^@ http://purl.uniprot.org/uniprot/Q9QXG4 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:11150295, PubMed:16790548). Acetate is the preferred substrate but can also utilize propionate with a much lower affinity (PubMed:11150295).|||Inhibited by acetylation at Lys-661 and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3.|||Monomer.|||Reversibly acetylated at Lys-661 (PubMed:16790548). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3.|||cytosol http://togogenome.org/gene/10090:Top3b ^@ http://purl.uniprot.org/uniprot/Q3UJF5|||http://purl.uniprot.org/uniprot/Q9Z321 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the type IA topoisomerase family.|||Highly expressed in testis.|||Introduces a single-strand break via transesterification at a target site in duplex DNA. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand.|||Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Possesses negatively supercoiled DNA relaxing activity. http://togogenome.org/gene/10090:Vmn1r207 ^@ http://purl.uniprot.org/uniprot/A0A494BA14 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Lyar ^@ http://purl.uniprot.org/uniprot/Q08288 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis and ovary at 15.5 dpc (PubMed:20339383). May be differentially expressed during spermatogenesis. Detected first at P12, the early stage of spermatogenesis. Levels considerably increase at P16, corresponding to the development of pachytene spermatocytes (PubMed:23212345).|||Interacts with PRMT5; this interaction is direct (By similarity). Interacts with GNL2 and RPL23A (By similarity). Interacts with nucleolin/NCL; this interaction is direct (PubMed:19489080, PubMed:23212345). Interacts with phosphorylated IRF3; this interaction impairs IRF3 DNA-binding activity (By similarity).|||No visible phenotype. Mutant mice are fully fertile and show intact spermatogenesis.|||Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs (By similarity). Also acts at the level of transcription regulation. Along with PRMT5, binds embryonic globin promoter (By similarity). Represses the expression of embryonic globin Hbb-y gene (PubMed:25092918). In neuroblastoma cells, may also repress the expression of oxidative stress genes, including CHAC1, HMOX1, SLC7A11, ULBP1 and that encoding the small nucleolar RNA SNORD41 (By similarity). Preferentially binds to a DNA motif containing 5'-GGTTAT-3' (By similarity). Negatively regulates the antiviral innate immune response by targeting IRF3 and impairing its DNA-binding activity (By similarity). In addition, inhibits NF-kappa-B-mediated expression of pro-inflammatory cytokines (By similarity). Stimulates phagocytosis of photoreceptor outer segments by retinal pigment epithelial cells (PubMed:25735755). Prevents NCL self-cleavage, maintaining a normal steady-state level of NCL protein in undifferentiated embryonic stem cells (ESCs), which in turn is essential for ESC self-renewal (PubMed:19489080).|||Predominantly expressed in testis, in germ cells, and at a moderate level in spleen, liver and lung (at protein level) (PubMed:19489080, PubMed:23212345, PubMed:24990247). Very high levels in spermatogonia, spermatocytes and round spermatids, but not in testicular sperm and mature sperm (at protein level) (PubMed:20339383, PubMed:23212345, PubMed:24990247). Expressed in ovary (PubMed:20339383). Expressed in the retina, including in photoreceptor outer segments (at protein level) (PubMed:25735755). Expressed in undifferentiated embryonic stem cells (PubMed:19489080, PubMed:23212345).|||The N-terminal zinc-finger domains are required for the appropriate production of 28S rRNA and the formation of pre-60S particles.|||nucleolus|||photoreceptor outer segment http://togogenome.org/gene/10090:Psmd14 ^@ http://purl.uniprot.org/uniprot/O35593 ^@ Function|||Similarity|||Subunit ^@ Belongs to the peptidase M67A family. PSMD14 subfamily.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD4, a base containing 6 ATPases and few additional components. Within the complex, PSMD4 interacts with subunit PSMD7 through their respective MPN domain. Interacts with TXNL1.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. The PSMD14 subunit is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains within the complex. Plays a role in response to double-strand breaks (DSBs): acts as a regulator of non-homologous end joining (NHEJ) by cleaving 'Lys-63'-linked polyubiquitin, thereby promoting retention of JMJD2A/KDM4A on chromatin and restricting TP53BP1 accumulation. Also involved in homologous recombination repair by promoting RAD51 loading. http://togogenome.org/gene/10090:Tmed9 ^@ http://purl.uniprot.org/uniprot/Q6PDC2|||http://purl.uniprot.org/uniprot/Q99KF1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to be involved in vesicular protein trafficking, mainly in the early secretory pathway. In COPI vesicle-mediated retrograde transport involved in the coatomer recruitment to membranes of the early secretory pathway. Increases coatomer-dependent activity of ARFGAP2. Thought to play a crucial role in the specific retention of p24 complexes in cis-Golgi membranes; specifically contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network. May be involved in organization of intracellular membranes, such as of the ER-Golgi intermediate compartment and the Golgi apparatus. Involved in ER localization of PTPN2 (By similarity).|||Belongs to the EMP24/GP25L family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Membrane|||Monomer and homodimer in endoplasmic reticulum. Predominantly monomeric and to lesser extent homodimeric in endoplasmic reticulum-Golgi intermediate compartment and cis-Golgi network. Probably oligomerizes with other members of the EMP24/GP25L family such as TMED2, TMED7 and TMED10. Interacts with TMED5. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED9. Interacts with PTPN2 and SPAST. Interacts with STX17; the interaction is direct (By similarity).|||N-linked glycosylated containing high mannose.|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Rgmb ^@ http://purl.uniprot.org/uniprot/Q7TQ33 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds.|||Belongs to the repulsive guidance molecule (RGM) family.|||Cell membrane|||Detected in neonatal and adult dorsal root ganglion sensory neurons, spinal cord, and brain (at protein level). Also expressed at high levels in retinal ganglion cells of developing mouse, extending to the optic nerve (at protein level). Expressed in testis, epididymis, ovary, uterus, and pituitary.|||Expressed in the developing nervous system. Expression is restricted to a subset of individual neurons in the mid- and hindbrain regions. At 10.5 dpc, expression level increases and extends further into the forebrain. The segmented pattern of expression becomes more refined and is indicative of peripheral nervous system labelling. Not detected in the area of motoneuron differentiation. Expression could be restricted to postmitotic neurons. Also expressed in fetal dorsal root ganglion, dorsal horn, in the dorsomedial mantle layer of the spinal cord, alar plate of the myelencephalon, marginal layer of the mesencephalon, basal plate of the pons, and cerebellar primordia, as well as the cortex of the olfactory lobe, retina, and olfactory epithelium. In the developing eye, expressed in differentiating ganglion cells and later in the development, also in amacrine cells. In adult, expressed in scattered cells throughout the brain.|||GPI-anchored.|||Homooligomer. Interacts with DRGX. Interacts with BMP2 and BMP4. Interacts with the BMP type I receptors ACVR1, BMPR1A and BMPR1B and with the BMP type II receptor ACVR2B. The functional complex with its receptor NEO1/neogenin appears to be a heterotetramer with a 2:2 stoichiometry, RGM molecules acting as staples that bring two NEO1 receptors together without interacting themselves, this arrangement leads to activation of downstream signaling via RhoA.|||Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system. Acts as a bone morphogenetic protein (BMP) coreceptor that potentiates BMP signaling. Promotes neuronal adhesion. May inhibit neurite outgrowth (By similarity).|||Membrane raft http://togogenome.org/gene/10090:H4c4 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Serpina12 ^@ http://purl.uniprot.org/uniprot/Q7TMF5 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.|||Belongs to the serpin family.|||Expressed in visceral adipose tissues.|||Forms a stable complex with KLK7.|||Glycosylation slightly decreases affinity for heparin, but otherwise has no significant effect on KLK7 inhibitory activity or thermal stability of the protein.|||Inhibition of KLK7 is enhanced by heparin.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable. http://togogenome.org/gene/10090:Pramel29 ^@ http://purl.uniprot.org/uniprot/A2A958 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Tigar ^@ http://purl.uniprot.org/uniprot/Q8BZA9 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphoglycerate mutase family.|||Cytoplasm|||Expressed in olfactory bulb, cerebellum, and cortex (PubMed:24872551). Expressed in neurons and astrocytes (PubMed:24872551) (at protein level). Expressed in intestinal crypt (PubMed:23726973).|||Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate (By similarity). Acts as a negative regulator of glycolysis by lowering intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in the pentose phosphate pathway (PPP) activation and NADPH production (PubMed:23726973). Contributes to the generation of reduced glutathione to cause a decrease in intracellular reactive oxygen species (ROS) content, correlating with its ability to protect cells from oxidative or metabolic stress-induced cell death (PubMed:23726973). Plays a role in promoting protection against cell death during hypoxia by decreasing mitochondria ROS levels in a HK2-dependent manner through a mechanism that is independent of its fructose-bisphosphatase activity (By similarity). In response to cardiac damage stress, mediates p53-induced inhibition of myocyte mitophagy through ROS levels reduction and the subsequent inactivation of BNIP3 (PubMed:22044588). Reduced mitophagy results in an enhanced apoptotic myocyte cell death, and exacerbates cardiac damage (PubMed:22044588). Plays a role in adult intestinal regeneration; contributes to the growth, proliferation and survival of intestinal crypts following tissue ablation (PubMed:23726973). Plays a neuroprotective role against ischemic brain damage by enhancing PPP flux and preserving mitochondria functions (PubMed:24872551). Protects glioma cells from hypoxia- and ROS-induced cell death by inhibiting glycolysis and activating mitochondrial energy metabolism and oxygen consumption in a TKTL1-dependent and p53/TP53-independent manner. Plays a role in cancer cell survival by promoting DNA repair through activating PPP flux in a CDK5-ATM-dependent signaling pathway during hypoxia and/or genome stress-induced DNA damage responses (By similarity). Involved in intestinal tumor progression (PubMed:23726973).|||Interacts with HK2; the interaction increases hexokinase HK2 activity in a hypoxia- and HIF1A-dependent manner, resulting in the regulation of mitochondrial membrane potential, thus increasing NADPH production and decreasing intracellular ROS levels.|||Mice are viable and fertile and show no obvious developmental defects (PubMed:23726973). Following intestine ablation by gamma irradiation, adult mice display a reduction in the size and number of proliferating intestinal crypts and an increase in cell death (PubMed:23726973). Mice display reduced intestinal tumor progression compared to wild-type mice (PubMed:23726973). In response to ischemic myocardium injury, display an increase in the ability to stimulate myocyte mitophagy in ischemic border zones through a ROS-induced and BNIP3 activation dependent manner leading to a reduction of defective mitochondria and myocyte cell death, and hence a better recovery of cardiac function (PubMed:22044588).|||Mitochondrion|||Not expected to have any kinase activity.|||Nucleus|||Up-regulated by hypoxia in cardiac myocytes in a p53/TP53-dependent manner (PubMed:20935145). Up-regulated in ischemic cortex after reperfusion in a p53/TP5-independent manner (PubMed:24872551). Up-regulated in primary neurons by oxygen and glucose deprivation (OGD)/reoxygenation insult in a p53/TP5-independent manner (at protein level) (PubMed:24872551). Up-regulated in ischemic myocardium in a p53/TP5-dependent manner (PubMed:22044588). Up-regulated in small intestine after gamma irradiation damage (PubMed:23726973). http://togogenome.org/gene/10090:Fam169b ^@ http://purl.uniprot.org/uniprot/Q8CHT6 ^@ Similarity ^@ Belongs to the FAM169 family. http://togogenome.org/gene/10090:Ubxn6 ^@ http://purl.uniprot.org/uniprot/Q99PL6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Early endosome membrane|||Interacts with VCP through the PUB domain (via C-terminus) and VIM motif (via N-terminus); the interaction is direct. Forms a ternary complex with CAV1 and VCP. Interacts with SYVN1. Interacts with HERPUD1. Interacts with VCPKMT. May interact with DERL1. Interacts with PLAA, VCP and YOD1; may form a complex involved in macroautophagy. Interacts with LMAN1.|||Late endosome membrane|||Lysosome membrane|||May negatively regulate the ATPase activity of VCP, an ATP-driven segregase that associates with different cofactors to control a wide variety of cellular processes. As a cofactor of VCP, it may play a role in the transport of CAV1 to lysosomes for degradation. It may also play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. Together with VCP and other cofactors, it may play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes.|||Membrane|||Nucleus|||The UBX domain lacks key residues critical for VCP binding.|||Widely expressed (at protein level). Highest expression in brain (at protein level).|||centrosome|||cytosol http://togogenome.org/gene/10090:Phc2 ^@ http://purl.uniprot.org/uniprot/Q9QWH1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a PRC1-like complex. Interacts with CBX4 (By similarity). Interacts with BMI1, PCGF2, PHC1 and RNF2 (PubMed:9627119, PubMed:16024804, PubMed:27827373). Interacts with CHTOP (PubMed:22872859). Interacts with the N-terminal region of the SP1 transcription factor and with MAPKAPK2 (By similarity).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility.|||Detected at 11.5 dpc in the developing brain, in the ventricular zones of the cortex and ganglionic eminences as well as in adult, in mature structures such as the granule cell layer of the dentate gyrus and cerebellum.|||HD1 motif interacts with SAM domain of PHC1.|||Isoform 2 is ubiquitously expressed in embryos and adult tissues at much higher level than isoform 1.|||Mice are viable and fertile but show posterior transformations of the axial skeleton and premature senescence of mouse embryonic fibroblast associated with derepression of Hox cluster genes and Cdkn2a genes, respectively. Mice lacking Phc2 and Phc1 die at an early gestational stage. Mice mutant for Phc1 and/or Phc2 demonstrate that Phc1 and Phc2 mutations affect synergistically the survival of embryos in a gene dosage-dependent manner and thus show functional redundancy of Phc1 and Phc2.|||Nucleus http://togogenome.org/gene/10090:Btbd7 ^@ http://purl.uniprot.org/uniprot/Q8CFE5 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a mediator of epithelial dynamics and organ branching by promoting cleft progression. Induced following accumulation of fibronectin in forming clefts, leading to local expression of the cell-scattering SNAIL2 and suppression of E-cadherin levels, thereby altering cell morphology and reducing cell-cell adhesion. This stimulates cell separation at the base of forming clefts by local, dynamic intercellular gap formation and promotes cleft progression.|||By fibronectin.|||Highly expressed in developing salivary glands at 13 dpc, a stage of particularly active salivary gland branching. Concentrated around the bottom and lower sides of forming clefts, while it is weakly or not expressed in other salivary epithelial regions. Also expressed in mesenchyme containing high levels of fibronectin.|||Nucleus|||Specifically expressed in embryonic epithelia. http://togogenome.org/gene/10090:Gsta4 ^@ http://purl.uniprot.org/uniprot/P24472 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Alpha family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Cytoplasm|||Homodimer.|||On the basis of immunological and kinetics data, GST 5.7 is distinct from alpha, mu and pI classes of GTS. However it has been postulated that this protein may be part of a distinct subgroup within this alpha class.|||The N-terminus is blocked.|||The variations were found from AA sequencing and imply there are multiple forms of this protein. These variations are likely to be sex-linked and tissue specific. http://togogenome.org/gene/10090:Prkab2 ^@ http://purl.uniprot.org/uniprot/Q6PAM0 ^@ Function|||PTM|||Similarity|||Subunit ^@ AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3).|||Belongs to the 5'-AMP-activated protein kinase beta subunit family.|||Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3) (By similarity).|||Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. http://togogenome.org/gene/10090:Chchd1 ^@ http://purl.uniprot.org/uniprot/Q9CQA6 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS37 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Uqcc3 ^@ http://purl.uniprot.org/uniprot/Q3V2E3|||http://purl.uniprot.org/uniprot/Q8K2T4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III(CIII) or cytochrome b-c1 complex). Interacts with UQCC1 (PubMed:35977508). Forms a complex, named COMC, composed of UQCC1, UQCC2; UQCC3 and UQCC4; mediates MT-CYB hemylation and association with the first nuclear-encoded complex III subunit UQCRQ (PubMed:35977508).|||Belongs to the UQCC3 family.|||Membrane|||Mitochondrion inner membrane|||Probably cleaved by OMA1 under mitochondrial stress conditions.|||Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex), mediating cytochrome b recruitment and probably stabilization within the complex. Thereby, plays an important role in ATP production by mitochondria. Cardiolipin-binding protein, it may also control the cardiolipin composition of mitochondria membranes and their morphology. http://togogenome.org/gene/10090:Prxl2a ^@ http://purl.uniprot.org/uniprot/Q9CYH2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peroxiredoxin-like PRXL2 family. PRXL2A subfamily.|||Cytoplasm|||Expressed in kidney, liver, skin, and brain (PubMed:19951071). Widely expressed with highest levels detected in adipose tissue (PubMed:26438880).|||Involved in redox regulation of the cell (By similarity). Acts as an antioxidant (By similarity). Inhibits TNFSF11-induced NFKB1 and JUN activation and osteoclast differentiation (By similarity). May affect bone resorption and help to maintain bone mass (By similarity). Acts as a negative regulator of macrophage-mediated inflammation by inhibiting macrophage production of inflammatory cytokines, probably through suppression of the MAPK signaling pathway (PubMed:26438880).|||Secreted|||The active site cysteines correspond to the redox-active cysteines of peroxiredoxins. http://togogenome.org/gene/10090:Fam205a4 ^@ http://purl.uniprot.org/uniprot/C0HKD1|||http://purl.uniprot.org/uniprot/C0HKD2|||http://purl.uniprot.org/uniprot/C0HKD3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Ramac ^@ http://purl.uniprot.org/uniprot/Q9CQY2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAM family.|||Interacts with RNMT; this interaction enhances mRNA binding and cap methyltransferase activity.|||Nucleus|||Regulatory subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Promotes the recruitment of the methyl donor, S-adenosyl-L-methionine, to RNMT. Regulates RNMT expression by a post-transcriptional stabilizing mechanism. Binds RNA. http://togogenome.org/gene/10090:Mllt1 ^@ http://purl.uniprot.org/uniprot/Q9ERL0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Tspo ^@ http://purl.uniprot.org/uniprot/P50637 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TspO/BZRP family.|||By dimethyl sulfoxide and diazepam.|||Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides. Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:9832438, PubMed:24814875), but its precise physiological role is controversial. According to some reports, it is not required for steroid hormone biosynthesis (PubMed:24174323, PubMed:24936060).|||Detected in liver (at protein level). Ubiquitous.|||Interacts with TSPOAP1. Interacts with MOST-1. May interact with STAR.|||Membrane|||Mitochondrion membrane|||No obvious phenotype. Mice are viable and fertile and present only very minor changes in gonadal and adrenal steroid hormone production. testis-specific gene disruption (PubMed:24174323) does not affect testosterone production, gametogenesis and male fertility. http://togogenome.org/gene/10090:Or10ab4 ^@ http://purl.uniprot.org/uniprot/Q7TRV1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dnajb14 ^@ http://purl.uniprot.org/uniprot/Q149L6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway. Acts by determining HSPA8/Hsc70's ATPase and polypeptide-binding activities. Can also act independently of HSPA8/Hsc70: together with DNAJB12, acts as a chaperone that promotes maturation of potassium channels KCND2 and KCNH2 by stabilizing nascent channel subunits and assembling them into tetramers. While stabilization of nascent channel proteins is dependent on HSPA8/Hsc70, the process of oligomerization of channel subunits is independent of HSPA8/Hsc70. When overexpressed, forms membranous structures together with DNAJB12 and HSPA8/Hsc70 within the nucleus; the role of these structures, named DJANGOs, is still unclear.|||Belongs to the DnaJ family. DNAJB12/DNAJB14 subfamily.|||Endoplasmic reticulum membrane|||Interacts (via J domain) with HSPA8/Hsc70. Forms a multiprotein complex, at least composed of DNAJB12, DNAJB14, HSPA8/Hsc70 and SGTA; interaction with DNAJB14 and HSPA8/Hsc70 is direct.|||Nucleus membrane http://togogenome.org/gene/10090:Tex10 ^@ http://purl.uniprot.org/uniprot/Q3URQ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IPI1/TEX10 family.|||Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity). Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148 (PubMed:22872859). Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts with pre-60S ribosome particles (By similarity).|||Cytoplasm|||Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Asap1 ^@ http://purl.uniprot.org/uniprot/Q9QWY8 ^@ Activity Regulation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2).|||Cytoplasm|||Expressed in all tissues examined but a most abundant expression was found in the testis, brain, lung and spleen. A heightened expression was seen in the adipose tissue from obese (ob) and diabetic (db) animals.|||Golgi apparatus|||Homodimer. Interacts with SRC and CRK. Interacts with RAB11FIP3. Interacts with PTK2B/PYK2. Interacts with REPS2; the interaction is direct (PubMed:12149250). Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport (By similarity).|||May function as a signal transduction protein involved in the differentiation of fibroblasts into adipocytes and possibly other cell types. Posseses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6. May coordinate membrane trafficking with cell growth or actin cytoskeleton remodeling by binding to both SRC and PIP2. Part of the ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which direct preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (By similarity).|||Membrane|||Phosphorylated on tyrosine residues by SRC.|||The PH domain most probably contributes to the phosphoinositide-dependent regulation of ADP ribosylation factors.|||trans-Golgi network http://togogenome.org/gene/10090:Hsd17b10 ^@ http://purl.uniprot.org/uniprot/Q99N15 ^@ Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. http://togogenome.org/gene/10090:Lefty1 ^@ http://purl.uniprot.org/uniprot/Q64280 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TGF-beta family.|||By 8.0 dpc, expressed exclusively on the left side of developing embryos with expression predominantly in the prospective floor plate (PFP). Weak expression in the lateral-plate mesoderm (LPM).|||Required for left-right axis determination as a regulator of LEFTY2 and NODAL.|||Secreted|||The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner. http://togogenome.org/gene/10090:Hnrnpk ^@ http://purl.uniprot.org/uniprot/B2M1R6|||http://purl.uniprot.org/uniprot/P61979|||http://purl.uniprot.org/uniprot/Q3U9Q3|||http://purl.uniprot.org/uniprot/Q5FWJ5 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ By DNA damage. This up-regulation is due to protein stabilization. The constitutive protein levels are controlled by MDM2-mediated ubiquitination and degradation via the proteasome pathway.|||Cytoplasm|||Identified in the spliceosome C complex (By similarity). Interacts with ANKRD28 and RBM42 (By similarity). Interacts with DDX1 (By similarity). Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation (By similarity). Interacts with p53/TP53 (By similarity). Interacts with ZIK1 (PubMed:8910362). Interacts with BRDT (PubMed:22570411). Interacts with IVNS1ABP (By similarity). Interacts with PPIA/CYPA (By similarity). Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, ZNF827 and HNRNPL (By similarity).|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.|||One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (By similarity).|||Sumoylated by CBX4. Sumoylation is increased upon DNA damage, such as that produced by doxorubicin, etoposide, UV light and camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under these conditions (By similarity).|||Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly-ubiquitination (By similarity).|||nucleoplasm|||podosome http://togogenome.org/gene/10090:Pkia ^@ http://purl.uniprot.org/uniprot/P63248 ^@ Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the PKI family.|||Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.|||Present at high levels in skeletal muscle and brain but is present at lower levels in heart, testis and liver.|||The inhibitory site contains regions very similar to the hinge regions (sites that directly interact with the enzyme active site) and 'pseudosubstrate site' of the regulatory chains; but, unlike these chains, PKI does not contain cAMP-binding sites. The arginine residues within the inhibitory site are essential for inhibition and recognition of the enzyme active site (By similarity). http://togogenome.org/gene/10090:Ufsp1 ^@ http://purl.uniprot.org/uniprot/Q9CZP0 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase C78 family.|||Thiol-dependent isopeptidase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins.|||Widely expressed. Expressed at higher level in brain, heart, kidney and skeletal muscle. http://togogenome.org/gene/10090:Prl7c1 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0E8|||http://purl.uniprot.org/uniprot/Q9CRB5 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Detectable throughout the second half of gestation.|||Expressed exclusively in the placenta. Expressed in spongiotrophoblast cells and trophoblast giant cells of the junctional zone and in labyrinthine trophoblast.|||Secreted http://togogenome.org/gene/10090:AW209491 ^@ http://purl.uniprot.org/uniprot/Q91WD4 ^@ Similarity ^@ Belongs to the UPF0415 family. http://togogenome.org/gene/10090:Prpf8 ^@ http://purl.uniprot.org/uniprot/Q99PV0 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains a region with structural similarity to RNase H, but lacks RNase H activity.|||Contains a region with structural similarity to reverse transcripase, presenting the classical thumb, fingers and palm architecture, but lacks enzyme activity, since the essential metal-binding residues are not conserved.|||Contains a region with structural similarity to type-2 restriction endonucleases, but the residues that would bind catalytic metal ions in endonucleases are instead involved in hydrogen bonds that stabilize the protein structure.|||During embryogenesis, is highly expressed at day 9.5 of gestation, and its expression decreases progressively during embryogenesis.|||Nucleus|||Nucleus speckle|||Part of the U5 snRNP complex (By similarity). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (By similarity). Component of the U5.U4atac/U6atac snRNP complexes in U12-dependent spliceosomes (By similarity). Within the minor spliceosome, which acts on U12-type introns, interacts with PPIL2 and RBM48 (By similarity). Core component of U2-type precatalytic, catalytic and postcatalytic spliceosomal complexes (By similarity). Found in a mRNA splicing-dependent exon junction complex (EJC) with SRRM1 (By similarity). Interacts with U5 snRNP proteins SNRP116 and SNRNP40 (By similarity). Interacts with EFTUD2 (By similarity). Interacts (via the MPN (JAB/Mov34) domain) with PRPF3 ('Lys-63'-linked polyubiquitinated); may stabilize the U4/U6-U5 tri-snRNP complex (By similarity). Interacts (via RNase H homology domain) with AAR2 (By similarity). Interacts with RPAP3 and URI1 in a ZNHIT2-dependent manner (By similarity). Interacts with C9orf78 (By similarity). Interacts with SNRNP200 (By similarity). Interacts with TSSC4; the interaction is direct (By similarity).|||Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome. Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site.|||Strongly expressed in testis (preferentially in the outer cell layer), and moderately in ovary (preferentially in granulosa cells).|||The MPN (JAB/Mov34) domain has structural similarity with deubiquitinating enzymes, but lacks the residues that would bind the catalytic metal ion.|||The MPN (JAB/Mov34) domain mediates interaction with TSSC4 and SNRNP200. Has structural similarity with deubiquitinating enzymes, but lacks the residues that would bind the catalytic metal ion. http://togogenome.org/gene/10090:Mrgpra2a ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Z0|||http://purl.uniprot.org/uniprot/Q91WW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed in a subset of sensory neurons that includes nociceptors. Expressed in the subclass of non-peptidergic sensory neurons that are IB4(+) and VR1(-).|||Membrane|||Orphan receptor. May be a receptor for RFamide-family neuropeptides such as NPFF and NPAF, which are analgesic in vivo. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Gsdmc2 ^@ http://purl.uniprot.org/uniprot/Q2KHK6 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gasdermin family.|||By type 2 cytokines in response to type-2 immunity following worm infection.|||Cell membrane|||Cleavage by CASP8 relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-C2, N-terminal) that initiates pyroptosis (PubMed:34290141).|||Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.|||Pore-forming protein that causes membrane permeabilization and pyroptosis in response to type-2 immunity (PubMed:34290141). Produced by the cleavage of gasdermin-D in response to type-2 immunity following worm infection (PubMed:34290141). After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids (By similarity). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis and lytic cell death in enterocytes (PubMed:34290141).|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C2, N-terminal) following cleavage by caspase CASP8 in response to type-2 immunity following worm infection (PubMed:34290141).|||This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C2, N-terminal) binds to membranes and forms pores, triggering pyroptosis.|||cytosol http://togogenome.org/gene/10090:Mif ^@ http://purl.uniprot.org/uniprot/P34884|||http://purl.uniprot.org/uniprot/Q545F0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MIF family.|||Cytoplasm|||Homotrimer (PubMed:16780921). Interacts with CD74 and CXCR2 extracellular domain and COPS5 (PubMed:19188446). Interacts with the USO1 and BNIPL (By similarity).|||Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens (By similarity). The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense (By similarity). Counteracts the anti-inflammatory activity of glucocorticoids (By similarity). Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known (PubMed:19188446, PubMed:10933783, PubMed:16780921). It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (PubMed:19188446, PubMed:10933783, PubMed:16780921).|||Secreted http://togogenome.org/gene/10090:Timd2 ^@ http://purl.uniprot.org/uniprot/Q8R183 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma. The human genomic locus appears to lack the Timd2 gene.|||Belongs to the immunoglobulin superfamily. TIM family.|||Cell membrane|||Cell surface glycoprotein that participates in iron homeostasis in the liver, the kidney, the retina and oligodendrocytes by acting as a receptor of H-ferritin (PubMed:16203866, PubMed:33065090). Mechanistically, mediates iron-containing ferritin uptake via an endocytic pathway, trafficking to endosomes and subsequently to lysosomes (PubMed:16043519, PubMed:21886823). Plays also an important role in the regulation of Th2 immunity (PubMed:16043519). Receptor for SEMA4A involved in the regulation of T-cell function, enhancing T-cell activation (PubMed:12374982).|||Deletion mutants lead to ferritin accumulation and iron overload in the retina leading to retinal lesions.|||Expressed on late differentiated Th2 cells (PubMed:16043519). Expressed also on all splenic B-cells, with increased levels on germinal center B-cells, in the liver, especially in bile duct epithelial cells, and in renal tubule cells (PubMed:16203866). Within retina, mainly expressed in Mueller cells (PubMed:33065090).|||Homodimer. http://togogenome.org/gene/10090:Slc12a2 ^@ http://purl.uniprot.org/uniprot/E9QM38|||http://purl.uniprot.org/uniprot/P55012 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated following phosphorylation by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4).|||Basolateral cell membrane|||Belongs to the SLC12A transporter family.|||Cation-chloride cotransporter which mediates the electroneutral transport of chloride, potassium and/or sodium ions across the membrane (PubMed:14563843, PubMed:32658972). Plays a vital role in the regulation of ionic balance and cell volume (By similarity).|||Homodimer.|||Membrane|||Phosphorylated at Thr-196, Thr-200 and Thr-205 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), promoting its activity.|||The RFXV motifs mediate binding with OXSR1/OSR1 and STK39/SPAK.|||Widely expressed. High expression found in the cochlea, cochlear lateral wall, and the choroid plexus (PubMed:32294086). Lower expression found in the cerebellum and the cortex (PubMed:32294086). http://togogenome.org/gene/10090:Upf1 ^@ http://purl.uniprot.org/uniprot/Q9EPU0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA2/NAM7 helicase family.|||Cytoplasm|||Embryos are viable in pre-implantation period, show complete loss of NMD but are resorbed shortly after implantation.|||Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Associates with the SGM1C complex; is phosphorylated by the complex kinase component SGM1. Part of a complex composed of SMG1, DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein to facilitate SMG1 phosphorylation of UPF1 (By similarity). Interacts with UPF2. Interacts with UPF3A and UPF3B. Interacts with EST1A. Interacts with SLBP. Interacts (when hyperphosphorylated) with PNRC2. Interacts with AGO1 and AGO2. Interacts with GSPT2. Interacts with isoform 1 and isoform 5 of ADAR/ADAR1. Interacts with SMG7. Interacts with ZC3H12A; this interaction occurs in a mRNA translationally active- and termination-dependent manner and is essential for ZC3H12A-mediated degradation of target mRNAs. Interacts with CPSF6. Interacts with MOV10; the interaction is direct and RNA-dependent. Interacts with SHFL; the interaction increases in the presence of RNA. Interacts with UPF2 and DDX4; interactions are mediated by TDRD6 (PubMed:27149095). Interacts with DHX34 and PABPC1/PABP1; the interactions are RNA-independent (By similarity). Interacts with RBM46 (PubMed:36001654).|||Localizes in male germ cells.|||Nucleus|||P-body|||Phosphorylated by SMG1; required for formation of mRNA surveillance complexes.|||RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs (By similarity). Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD (By similarity). Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (By similarity). In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD (By similarity). Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors (By similarity). UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (By similarity). Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (By similarity). For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (By similarity). The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (By similarity). Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (PubMed:27149095). Also capable of unwinding double-stranded DNA and translocating on single-stranded DNA (By similarity).|||The [ST]-Q motif constitutes a recognition sequence for kinases from the PI3/PI4-kinase family.|||Weakly expressed in neonatal testes and expression increases during the development of spermatocytes and spermatids, in the late meiotic and postmeiotic stages of spermatogenesis.|||perinuclear region http://togogenome.org/gene/10090:Glb1l3 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSK9|||http://purl.uniprot.org/uniprot/A2RSQ1 ^@ Similarity ^@ Belongs to the glycosyl hydrolase 35 family. http://togogenome.org/gene/10090:BC005624 ^@ http://purl.uniprot.org/uniprot/Q3TQI7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TLS1 family.|||Component of the spliceosome (By similarity). Interacts with SNRNP200; the interaction is direct (By similarity). Interacts with PRPF8 (By similarity).|||Nucleus|||Plays a role in pre-mRNA splicing by promoting usage of the upstream 3'-splice site at alternative NAGNAG splice sites; these are sites featuring alternative acceptor motifs separated by only a few nucleotides (By similarity). May also modulate exon inclusion events (By similarity). PPlays a role in spliceosomal remodeling by displacing WBP4 from SNRNP200 and may act to inhibit SNRNP200 helicase activity (By similarity). Binds U5 snRNA (By similarity). Required for proper chromosome segregation (By similarity). Not required for splicing of shelterin components (By similarity).|||centromere http://togogenome.org/gene/10090:Lrrc1 ^@ http://purl.uniprot.org/uniprot/Q80VQ1 ^@ Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with DLG1. May form a complex with DLG1 and ERBIN, where interaction between LRRC1 and ERBIN is indirect (By similarity).|||Membrane http://togogenome.org/gene/10090:Ccn2 ^@ http://purl.uniprot.org/uniprot/P29268 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCN family.|||By growth factors.|||Major connective tissue mitoattractant secreted by vascular endothelial cells. Promotes proliferation and differentiation of chondrocytes (By similarity). Mediates heparin- and divalent cation-dependent cell adhesion in many cell types including fibroblasts, myofibroblasts, endothelial and epithelial cells (By similarity). Enhances fibroblast growth factor-induced DNA synthesis (By similarity).|||Monomer (By similarity). Interacts with TSKU (PubMed:30232710).|||Secreted|||Testis, spleen, kidney, lung, heart, and brain (lowest level in testis and highest in lung).|||extracellular matrix http://togogenome.org/gene/10090:Polr2l ^@ http://purl.uniprot.org/uniprot/P62876 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2L/RBP10 is part of the core element with the central large cleft (By similarity).|||Nucleus http://togogenome.org/gene/10090:Eci1 ^@ http://purl.uniprot.org/uniprot/P42125 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species.|||Belongs to the enoyl-CoA hydratase/isomerase family.|||Homotrimer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Kyat3 ^@ http://purl.uniprot.org/uniprot/Q71RI9 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA), an intermediate in the tryptophan catabolic pathway which is also a broad spectrum antagonist of the three ionotropic excitatory amino acid receptors among others (PubMed:19029248). May catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond (PubMed:19029248). Has transaminase activity towards L-kynurenine, tryptophan, phenylalanine, serine, cysteine, methionine, histidine, glutamine and asparagine with glyoxylate as an amino group acceptor (in vitro). Has lower activity with 2-oxoglutarate as amino group acceptor (in vitro) (PubMed:19029248).|||Expressed from postnatal day (PND) 7 and peaks in adult.|||Homodimer.|||Kynurenine transamination is competitively inhibited by cysteine, glutamine, histidine, methionine, leucine, or phenylalanine.|||Widely expressed, with higher expression levels in liver, kidney, heart and neuroendocrine tissues. http://togogenome.org/gene/10090:Foxk1 ^@ http://purl.uniprot.org/uniprot/P42128 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed at 13.5 dpc in developing muscle, limbs, trunk, and heart.|||Expressed in tissues and cells in which the myoglobin gene is transcriptionally active including cardiac and skeletal myocytes, brain and kidney (PubMed:8007964, PubMed:9271401). In the adult brain, expressed in the piriform cortex and the indusium griseum. In the hippocampus, expression is localized to the dentate gyrus and CA3 area (PubMed:16376864). In the cerebellum, expression is confined to the Purkinje cell layer (PubMed:16376864). Present in neuroretinal cells: expressed in rod bipolar cells, amacrine cells and ganglion cells (at protein level) (PubMed:23714736).|||Interacts with SIN3A and SIN3B (via PAH2) to form a complex which represses transcription (PubMed:10620510). Component of SIN3A-, but not SIN3B-, containing multiprotein complexes (PubMed:25402684). Interacts with FOXO4 and MEF2C; both interactions inhibit FOXO4 and MEF2C transactivation activity (PubMed:22956541). Interacts (when phosphorylated) with YWHAE/14-3-3-epsilon; promotes sequestration in the cytoplasm and leads to impaired ability to bind DNA (PubMed:29861159). Interacts with FHL2 (PubMed:20013826). Interacts with SRF (By similarity). Interacts with DVL2 and DVL3; the interaction induces DVL2 nuclear translocation (By similarity). Interacts with BAP1 (when phosphorylated) (By similarity).|||Mutants exhibit a growth deficiency and a severe impairment in skeletal muscle regeneration following injury (PubMed:12446708, PubMed:10792059). They show atrophic skeletal muscles and their satellite cell function is impaired (PubMed:10792059). Double knockouts of CDKN1A and FOXK1 don't show significant differences compared to wild-type (PubMed:12446708).|||Nucleus|||Phosphorylation by GSK3 (GSK3A or GSK3B) promotes interaction with YWHAE/14-3-3-epsilon and retention in the cytoplasm (PubMed:29861159). In response to mTORC1 signaling, phosphorylation by GSK3 is prevented, leading to translocation to the nucleus (PubMed:29861159).|||The mode of regulation of FOXK1 by mTORC1 is controversial. According to a first report, mTORC1 signaling promotes phosphorylation of FOXK1 and nuclear exclusion (PubMed:25402684). According to a second report, mTORC1 signaling prevents phosphorylation by GSK3 (GSK3A or GSK3B), thereby promoting translocation to the nucleus (PubMed:29861159).|||Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (PubMed:25402684, PubMed:29861159, PubMed:30700909). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:25402684, PubMed:29861159, PubMed:30700909). Together with FOXK2, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (PubMed:30700909). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (PubMed:30700909). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (PubMed:30700909). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (PubMed:29861159). Together with FOXK2, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (PubMed:25402684). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (PubMed:8007964, PubMed:9271401, PubMed:12446708, PubMed:22956541). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (PubMed:8007964, PubMed:9271401). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (PubMed:12446708, PubMed:22956541). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (PubMed:9271401, PubMed:22956541). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (PubMed:10792059). Represses myogenic differentiation by inhibiting MEFC activity (PubMed:22956541). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (By similarity). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (By similarity). http://togogenome.org/gene/10090:Alg10b ^@ http://purl.uniprot.org/uniprot/Q3UGP8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ALG10 glucosyltransferase family.|||Cell membrane|||Interacts with KCNH1 and KCNH2.|||Putative alpha-1,2-glucosyltransferase, which adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(2)Man(9)GlcNAc(2)-PP-Dol (By similarity). When coupled to KCNH2 may reduce KCNH2 sensitivity to classic proarrhythmic drug blockade, possibly by mediating glycosylation of KCNH2 (By similarity). Has a role in maintenance of cochlear outer hair cell function (PubMed:24303013). http://togogenome.org/gene/10090:Lnx2 ^@ http://purl.uniprot.org/uniprot/Q91XL2 ^@ Domain|||Subunit|||Tissue Specificity ^@ Interacts with the phosphotyrosine interaction domain of NUMB.|||The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient.|||Widely expressed. http://togogenome.org/gene/10090:Gulo ^@ http://purl.uniprot.org/uniprot/P58710 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the oxygen-dependent FAD-linked oxidoreductase family.|||Endoplasmic reticulum membrane|||Highly expressed in liver.|||Microsome membrane|||Oxidizes L-gulono-1,4-lactone to hydrogen peroxide and L-xylo-hexulonolactone which spontaneously isomerizes to L-ascorbate. http://togogenome.org/gene/10090:Glce ^@ http://purl.uniprot.org/uniprot/Q9EPS3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the D-glucuronyl C5-epimerase family.|||Converts D-glucuronic acid residues adjacent to N-sulfate sugar residues to L-iduronic acid residues, both in maturing heparan sulfate (HS) and heparin chains. This is important for further modifications that determine the specificity of interactions between these glycosaminoglycans and proteins.|||Golgi apparatus membrane|||Homodimer (By similarity). Interacts with HS2ST1 (PubMed:11687650).|||Perinatal lethality. Pups die shortly after birth, apparently from respiratory failure. Mice show immature lung structure, lack kidneys, have abnormally small thymus and spleen, defects in inguinal lymph node development and in blood vessel formation proximal to the inguinal lymph nodes, and display important skeletal deficiencies. Mutant mice have heparan and heparin chains that are deficient in iduronic acid residues, and that therefore have altered O-sulfation patterns.|||Widely expressed with highest levels in lung and lowest levels in spleen. http://togogenome.org/gene/10090:Anxa11 ^@ http://purl.uniprot.org/uniprot/P97384 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||Cytoplasm|||Interacts with S100A6. Interacts with PDCD6 in a calcium-dependent manner. Interacts with KIF23 during cytokinesis.|||Melanosome|||Nucleus envelope|||Required for midbody formation and completion of the terminal phase of cytokinesis (By similarity). Binds specifically to calcyclin in a calcium-dependent manner.|||nucleoplasm|||spindle http://togogenome.org/gene/10090:Atoh8 ^@ http://purl.uniprot.org/uniprot/Q99NA2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains a degenerate basic motif not likely to bind DNA.|||Cytoplasm|||Efficient DNA binding requires dimerization with another bHLH protein. Interacts with NEUROG3 and NEUROD1. Interacts with ZFPM2; mediates indirect interaction with GATA4. Forms a heterodimer with TCF3; repress transcription of TCF3 and TCF3/NEUROG3 dimer-induced transactivation of E box-dependent promoters.|||Expressed at high levels at 8.5 dpc and its expression level gradually decreases during embryogenesis. At 12.5 dpc, is expressed throughout the developing nervous system. It is expressed in both the ventricular zone and the mantle layer of the developing brain. At 14.5 dpc, expressed in the cortical plate as well as in other regions of the brain. Also expressed at a high level in the spinal cord and dorsal root ganglia. Expressed by almost all cells in the spinal cord and dorsal root ganglia at this stage. At later stages, expression is gradually restricted to several regions such as the hippocampus, cerebellum and retina. In the hippocampus, a high level of expression continues during embryogenesis until adulthood. Expressed in the CA1-CA3 regions and the dentate gyrus. At 18.5 dpc, expressed in cerebellum by Purkinje cells and granule cell precursors in the external granular layer (EGL). By postnatal day 4, expressed by aligned Purkinje cells and by the EGL and internal granular layer (IGL) cells. In the adult cerebellum, expressed at a high level by Purkinje cells and weakly by granule cells in the IGL. In developing retina, expressed in both the ganglion cell layer and the ventricular zone at 11.5 dpc and 17.5 dpc. Expression becomes very weak in the adult retina. Early in metanephric development, expressed in metanephric mesenchyme but not ureteric bud-derived cells, with overall expression being most abundant in the nephrogenic zone. From 14.5 dpc to birth, expressed at constant levels. By day 13, corresponding to the end of new nephron induction, expression levels begin to decline. By day 19, expression returned to fetal levels, and by day 40, the low level of expression that persisted into adulthood is established. In adult kidney, expression is restricted to podocytes. Expressed in pancreatic tissue from 12.5 dpc until 17.5 dpc. Is still detectable at low level,at postnatal day 1 and in isolated pancreatic islets in adult (PubMed:18560595).|||Expressed by subsets of mature neurons (PubMed:11733035). Expressed in kidney (podocytes) (PubMed:16937370). Expression is restricted to the atria, lung mesenchyme, and vascular smooth muscle (PubMed:23836893).|||Mice heterozygous survive to adulthood and present no phenotype (PubMed:18560595). The homozygous knockout of Atoh8 is embryonic lethal (PubMed:18560595).|||Nucleus|||Nucleus speckle|||Specifically activated by bHLH factors.|||The bHLH domain mediates transcriptional repression by inhibiting TCF3 transcriptional activity through heterodimerization.|||Transcription factor that binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins (By similarity). Regulates endothelial cell proliferation, migration and tube-like structures formation (By similarity). Modulates endothelial cell differentiation through NOS3 (By similarity). May be implicated in specification and differentiation of neuronal cell lineages in the brain (PubMed:11733035). May participate in kidney development and may be involved in podocyte differentiation (PubMed:16937370). During early embryonic development is involved in tissue-specific differentiation processes that are dependent on class II bHLH factors and namely modulates the differentiation program initiated by the pro-endocrine factor NEUROG3 (PubMed:18560595). During myogenesis, may play a role during the transition of myoblasts from the proliferative phase to the differentiation phase (PubMed:24186058). Positively regulates HAMP transcription in two ways, firstly by acting directly on the HAMP promoter via E-boxes binding and indirectly through increased phosphorylation of SMAD protein complex (By similarity). Repress NEUROG3-dependent gene activation in a gene-specific manner through at least two mechanisms; requires only either the sequestering of a general partner such as TCF3 through heterodimerization, either also requires binding of the bHLH domain to DNA via a basic motif (PubMed:23938248). http://togogenome.org/gene/10090:Batf ^@ http://purl.uniprot.org/uniprot/O35284 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8(+) dendritic cells and class-switch recombination (CSR) in B-cells. Acts via the formation of a heterodimer with JUNB that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3'. The BATF-JUNB heterodimer also forms a complex with IRF4 (or IRF8) in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 (or IRF8) and activation of genes. Controls differentiation of T-helper cells producing interleukin-17 (Th17 cells) by binding to Th17-associated gene promoters: regulates expression of the transcription factor RORC itself and RORC target genes such as IL17 (IL17A or IL17B). Also involved in differentiation of follicular T-helper cells (TfH) by directing expression of BCL6 and MAF. In B-cells, involved in class-switch recombination (CSR) by controlling the expression of both AICDA and of germline transcripts of the intervening heavy-chain region and constant heavy-chain region (I(H)-C(H)). Following infection, can participate in CD8(+) dendritic cell differentiation via interaction with IRF4 and IRF8 to mediate cooperative gene activation. Regulates effector CD8(+) T-cell differentiation by regulating expression of SIRT1. Following DNA damage, part of a differentiation checkpoint that limits self-renewal of hematopoietic stem cells (HSCs): up-regulated by STAT3, leading to differentiation of HSCs, thereby restricting self-renewal of HSCs.|||Belongs to the bZIP family.|||Cytoplasm|||Detected in postnatal and adult lymphoid tissues such as thymus, spleen and lymph nodes. In thymus most concentrated expression is found in the immediate cortical layer. Differentially expressed during T-cell development in thymus. Highly expressed in Th17, Th1 and Th2 cells and in activated B-cells.|||Heterodimer; mainly heterodimerizes with JUNB. The BATF-JUNB heterodimer interacts with IRF4 and IRF8. Interacts (via bZIP domain) with IRF4 and IRF8; the interaction is direct. Also forms heterodimers with JUN and JUND. Interacts with IFI35.|||Mice are fertile and healthy. They display a normal thymus, spleen and lymph node development, and normal CD4(+) and CD8(+) T-cell development. They also show normal development of natural killer T-cells, B-cells, and conventional and plasmacytoid dendritic cells. They however show defects in T-helper 17 cells (Th17) differentiation and are resistant to experimental autoimmune encephalomyelitis. Loss of follicular T-helper cells (TfH), as well as less production of antibodies with switched isotypes in B-cells is also observed.|||Nucleus|||Phosphorylated on serine and threonine residues and at least one tyrosine residue. Phosphorylation at Ser-43 inhibit DNA binding activity and transforms it as a negative regulator of AP-1 mediated transcription.|||Up-regulated by STAT3 in response to DNA damage. Induces by IL12 at late effector stage. Down-regulated by STAT5 in follicular T-helper cells (TfH). http://togogenome.org/gene/10090:Hamp2 ^@ http://purl.uniprot.org/uniprot/Q80T19 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the hepcidin family.|||Highly expressed in the liver and to a much lesser extent in the heart. Also expressed in pancreas.|||Secreted|||Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. http://togogenome.org/gene/10090:Hadha ^@ http://purl.uniprot.org/uniprot/Q8BMS1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-569 and Lys-728 is observed in liver mitochondria from fasted mice but not from fed mice.|||Heterotetramer of 2 alpha/HADHA and 2 beta/HADHB subunits; forms the mitochondrial trifunctional enzyme (By similarity). Also purified as higher order heterooligomers including a 4 alpha/HADHA and 4 beta/HADHB heterooligomer which physiological significance remains unclear (By similarity). The mitochondrial trifunctional enzyme interacts with MTLN (PubMed:29949755).|||In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.|||In the central section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.|||Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA. Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity. Independently of the subunit beta, the trifunctional enzyme subunit alpha/HADHA also has a monolysocardiolipin acyltransferase activity. It acylates monolysocardiolipin into cardiolipin, a major mitochondrial membrane phospholipid which plays a key role in apoptosis and supports mitochondrial respiratory chain complexes in the generation of ATP. Allows the acylation of monolysocardiolipin with different acyl-CoA substrates including oleoyl-CoA for which it displays the highest activity.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Chct1 ^@ http://purl.uniprot.org/uniprot/Q9D979 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Exclusively expressed in testes.|||May play a role in regulation of apoptosis.|||The CHD1 helical C-terminal domain (CHCT) may bind DNA and nucleosomes. http://togogenome.org/gene/10090:Zfp14 ^@ http://purl.uniprot.org/uniprot/P10755 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Rgp1 ^@ http://purl.uniprot.org/uniprot/Q8BHT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RGP1 family.|||Forms a complex with RIC1; the interaction enhances RAB6A GTPase activity. Interacts with RIC1. Interacts with RAB6A; the interaction is direct with a preference for RAB6A-GDP. Interacts with RAB33B.|||Membrane|||The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP and may thereby required for efficient fusion of endosome-derived vesicles with the Golgi compartment. The RIC1-RGP1 complex participates in the recycling of mannose-6-phosphate receptors.|||cytosol http://togogenome.org/gene/10090:H2-T3 ^@ http://purl.uniprot.org/uniprot/Q05A75|||http://purl.uniprot.org/uniprot/Q8HWB4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Carmil1 ^@ http://purl.uniprot.org/uniprot/D3Z030|||http://purl.uniprot.org/uniprot/Q6EDY6 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CARMIL family.|||Cell membrane|||Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:16054028).|||Cytoplasm|||Homodimer (By similarity). Interacts (via C-terminus) with heterodimeric capping protein (CP); this interaction uncaps barbed ends capped by CP, enhances barbed-end actin polymerization and promotes lamellipodial formation and cell migration (PubMed:16054028). Interacts with MYO1E (By similarity). Interacts with TRIO (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||The C-terminus is necessary for localization to the cell membrane.|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Dyrk1a ^@ http://purl.uniprot.org/uniprot/A1L341|||http://purl.uniprot.org/uniprot/A9C475|||http://purl.uniprot.org/uniprot/Q61214 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on numerous tyrosine residues. Can also autophosphorylate on serine and threonine residues (in vitro) (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.|||Detected in brain (at protein level) (PubMed:22998443). Expressed in a variety of embryonic and adult tissues (PubMed:8975710). Expressed abundantly in neurons of the brain, spinal cord, and retina in developing embryos (PubMed:8975710). Expressed in the entorhinal, temporal and visual cortices and the hippocampus of the brain where is colocalizes with SEPTIN4 (PubMed:18938227). Expressed and extensively colocalizes with SEPTIN4 in apical dendrites of pyramidal cells (PubMed:18938227). Also expressed in Purkinje cells in the cerebellum in postnatal day 1 and adult mice (PubMed:18938227).|||Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:18938227, PubMed:20123978). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3 (By similarity). Plays an important role in double-strand breaks (DSBs) repair following DNA damage (By similarity). Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR) (By similarity). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (By similarity). May play a role in a signaling pathway regulating nuclear functions of cell proliferation (By similarity). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (PubMed:20167603). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (PubMed:20167603). This in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (PubMed:18938227).|||Inhibited by RANBP9.|||Interacts with RANBP9 (By similarity). Interacts with RAD54L2/ARIP4 (PubMed:15199138). Interacts with WDR68 (By similarity). Interacts with CRY2 (PubMed:20123978). Interacts with SIRT1 (PubMed:20167603).|||Nucleus speckle|||The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance its ability to phosphorylate the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II).|||The polyhistidine repeats act as targeting signals to nuclear speckles. http://togogenome.org/gene/10090:Gvin2 ^@ http://purl.uniprot.org/uniprot/Q80SU7 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.|||By interferons. Induced both in response to IFN type I (IFN-alpha and -beta) and IFN type II (IFN-gamma).|||Nucleus|||Widely expressed. Expressed at low basal level in lung, heart, thymus and spleen; at still lower level in liver, ovary, kidney and brain. Expressed at very weak level in testis. Undetectable in embryo.|||cytosol http://togogenome.org/gene/10090:Ilf2 ^@ http://purl.uniprot.org/uniprot/Q9CXY6 ^@ Developmental Stage|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromatin-interacting protein that forms a stable heterodimer with interleukin enhancer-binding factor 3/ILF3 and plays a role in several biological processes including transcription, innate immunity or cell growth (PubMed:10574923). Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. Together with ILF3, forms an RNA-binding complex that is required for mitotic progression and cytokinesis by regulating the expression of a cluster of mitotic genes. Mechanistically, competes with STAU1/STAU2-mediated mRNA decay. Also plays a role in the inhibition of various viruses including Japanese encephalitis virus or enterovirus 71 (By similarity) (PubMed:10574923).|||Cytoplasm|||Expressed in brain, kidney and ovary; highly expressed in testis, particularly within pachytene cells.|||Expression in testis begins with developmental differentiation of pachytene spermatocytes.|||Forms heterodimers with ILF3. ILF2-ILF3 heterodimers may also bind to PRKDC/XRCC7: this may stabilize the interaction of PRKDC/XRCC7 and the heterodimeric complex of G22P1/KU70 and XRCC5/KU80. Forms a complex with ILF3, YLPM1, KHDRBS1, RBMX, NCOA5 and PPP1CA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with IGF2BP1. Interacts with CRBN; this interaction promotes ubiquitination and subsequent degradation of ILF2.|||Intron retention.|||Nucleus|||Ubiquitinated at Lys-45 by CRBN with polyubiquitin chains by the CUL4-RING E3 ligase (CRL4-CRBN) and then degraded by the proteasome.|||nucleolus http://togogenome.org/gene/10090:Or9a7 ^@ http://purl.uniprot.org/uniprot/Q8VF30 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atg7 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQN4|||http://purl.uniprot.org/uniprot/Q3TM87|||http://purl.uniprot.org/uniprot/Q9D906 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by EP300.|||Belongs to the ATG7 family.|||Cytoplasm|||E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Facilitates LC3-I lipidation with phosphatidylethanolamine to form LC3-II which is found on autophagosomal membranes (By similarity). Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Also plays a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner (PubMed:29937374).|||E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress.|||Homodimer.|||Homodimer. Interacts with ATG3, FOXO1 and EP300 acetyltransferase. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5. Interacts with FOXO1 (By similarity). Forms intermediate conjugates with ATG8 family proteins such as GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, or GABARAPL1. Interacts with ATG12.|||Leads to hepatomegaly in liver and accumulation of abnormal organelles in hepatic cells (PubMed:15866887). Liver-specific knockout leads to loss of autophagy, increased accumulation of CRY1, decreased blood glucose levels due to impaired gluconeogenesis and the disruption of the circadian clock in the liver (PubMed:29937374).|||Preautophagosomal structure|||The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12.|||The N-terminal FAP motif (residues 11 to 13) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates.|||Widely expressed, especially in kidney, liver, lymph nodes and bone marrow. http://togogenome.org/gene/10090:Plcb3 ^@ http://purl.uniprot.org/uniprot/P51432|||http://purl.uniprot.org/uniprot/Q8CI86 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Ca(2+) ion per subunit.|||Cytoplasm|||Highly expressed in kidney, skeletal muscle, liver, lung, heart and brain.|||Interacts with SHANK2 (By similarity). Interacts with LPAR2 (By similarity).|||Membrane|||Nucleus|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. http://togogenome.org/gene/10090:Impg2 ^@ http://purl.uniprot.org/uniprot/Q80XH2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix; may participate in the maturation and maintenance of the light-sensitive photoreceptor outer segment. Binds heparin.|||Expressed in the retina (at protein level) (PubMed:12589770, PubMed:29777959). Expressed in the pineal gland (PubMed:12589770).|||Increasing expression in retina from 15 dpc to adulthood: expressed at P8 when photoreceptor outer segments are in active stages of elongation; elevated expression at P10 in the developing IPM and at P15 in the region adjacent to the retina pigment epithelium (RPE). From P18 to P35, more homogeneously present in the IPM surrounding both cones and rods.|||Photoreceptor inner segment membrane|||Photoreceptor outer segment membrane|||interphotoreceptor matrix http://togogenome.org/gene/10090:Cstdc6 ^@ http://purl.uniprot.org/uniprot/L7N257 ^@ Similarity ^@ Belongs to the cystatin family. http://togogenome.org/gene/10090:Cpt1a ^@ http://purl.uniprot.org/uniprot/P97742|||http://purl.uniprot.org/uniprot/Q3UGT1|||http://purl.uniprot.org/uniprot/Q7TQD5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A conformation change in the N-terminal region spanning the first 42 residues plays an important role in the regulation of enzyme activity by malonyl-CoA.|||Belongs to the carnitine/choline acetyltransferase family.|||Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion (PubMed:16169268, PubMed:17030509). Plays an important role in hepatic triglyceride metabolism (By similarity).|||Complete lethality during early embryogenesis. Heterozygous mice are prone to liver steatosis. Compared to wild-type, heterozygotes show minor differences in blood glucose levels and in serum free fatty acid levels after fasting.|||Homohexamer and homotrimer (By similarity). Identified in a complex that contains at least CPT1A, ACSL1 and VDAC1 (By similarity). Also identified in complexes with ACSL1 and VDAC2 and VDAC3 (By similarity).|||Inhibited by malonyl-CoA.|||Membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Taar1 ^@ http://purl.uniprot.org/uniprot/Q923Y8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for trace amines, including beta-phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonin. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase.|||Widely distributed throughout the brain. Strongly expressed in the mitral cell layer of the olfactory bulb, piriform cortex, the arcuate, motor, and mesencephalic trigeminal nuclei, lateral reticular and hypoglossal nuclei, cerebellar Purkinje cells, and ventral horn of the spinal cord. Moderately expressed in the frontal, entorhinal, and agranular cortices, the ventral pallidum, thalamus, hippocampus, several hypothalamic nuclei, ambiguus, dorsal raphe, and gigantocellular reticular nuclei. Weakly expressed in the septum, basal ganglia, amygdala, myelencephalon, and spinal cord dorsal horn. Particularly interesting is the moderate expression in several monoaminergic cell groups, namely the dorsal raphe, the locus coeruleus, and the ventral tegmental area. http://togogenome.org/gene/10090:D8Ertd738e ^@ http://purl.uniprot.org/uniprot/Q8R1F0 ^@ Function|||Similarity ^@ Belongs to the UPF0390 family.|||May have a potential role in hypercalcemia of malignancy. http://togogenome.org/gene/10090:Mis12 ^@ http://purl.uniprot.org/uniprot/Q9CY25 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mis12 family.|||Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Also interacts with KNL1, CBX3, CBX5, NDC80 and ZWINT.|||Part of the MIS12 complex which is required for normal chromosome alignment and segregation and for kinetochore formation during mitosis. Essential for proper kinetochore microtubule attachments.|||kinetochore http://togogenome.org/gene/10090:Pou3f1 ^@ http://purl.uniprot.org/uniprot/P21952 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the POU transcription factor family. Class-3 subfamily.|||Expressed in embryonal stem cells and in the developing brain (PubMed:1979677). Down-regulated in embryonic stem cells upon differentiation (PubMed:1979677). Expressed in the sciatic nerves at postnatal days P6 to P12 (PubMed:10068633).|||Nucleus|||Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') (PubMed:1979677, PubMed:1976514). Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters (PubMed:18505825). Acts as a transcriptional repressor of myelin-specific genes (By similarity). http://togogenome.org/gene/10090:Pjvk ^@ http://purl.uniprot.org/uniprot/Q0ZLH2 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gasdermin family.|||By noise exposure.|||In ear, it is detected in the organ of Corti and the spiral ganglion within the cochlea in the sensory areas of the vestibule (cristae ampullares of the semicircular ducts, and maculae of the saccule and utricle) and in the first 3 relays (cochlear nuclei, superior olivary complex and inferior colliculus) of the afferent auditory pathway (PubMed:16804542). Detected in hair cells of the cochlea and vestibule but not in neurons (PubMed:17329413, PubMed:28089576). In the afferent auditory pathway, it is present in the cell bodies of neurons but not in fiber bundles such as the trapezoid body in the brainstem (PubMed:16804542). Also detected in spiral ganglion cells, which form the auditory nerve and project to the cochlear nuclei in the brainstem (PubMed:16804542). Also present in the cochlear nuclei, the superior olive and the inferior colliculus (at protein level) (PubMed:16804542). Expressed in all the adult organs tested: brain, eye, inner ear, heart, lung, kidney, liver, intestine, testis and weakly in skeletal muscle (PubMed:16804542).|||Interacts with MAP1LC3B; interaction is direct (PubMed:30936319). Interacts with IQGAP1 (PubMed:28089576). Interacts with ROCK2 (PubMed:28089576). Interacts with TRIOBP (PubMed:28209736).|||Mice display progressive hearing loss caused by hypervulnerability to sound exposure (PubMed:17329413, PubMed:26544938). Cochleas display features of marked oxidative stress and impaired antioxidant defenses, and peroxisomes in hair cells show structural abnormalities after the onset of hearing (PubMed:26544938). Mice with conditional deletion in all sensory hair cells show auditory phenotypes with early-onset profound hearing loss and outer hair cell degeneration (PubMed:28089576, PubMed:28209736). Mice with conditional deletion in outer hair cells show auditory phenotypes with early-onset profound hearing loss (PubMed:28089576). Conditional deletion in adult outer hair cells causes a slowly progressive hearing loss associated with outer hair cells degeneration and delayed loss of inner hair cells (PubMed:28089576).|||Peroxisome membrane|||Peroxisome-associated protein required to protect auditory hair cells against noise-induced damage (PubMed:26544938, PubMed:30936319). Acts by regulating noise-induced peroxisome proliferation in auditory hair cells and neurons, and promoting autophagic degradation of damaged peroxisomes (pexophagy) (PubMed:26544938, PubMed:30936319). Noise overexposure increases reactive oxygen species (ROS) levels, causing oxidative damage to auditory hair cells and resulting in hearing loss (PubMed:30936319). PJVK acts as a ROS sensor that recruits the autophagy machinery to trigger pexophagy of peroxisomes damaged by oxidative stress (PubMed:30936319). In addition to pexophagy, also required to promote peroxisome proliferation in response to sound overstimulation (PubMed:26544938, PubMed:30936319).|||cilium http://togogenome.org/gene/10090:Zeb1 ^@ http://purl.uniprot.org/uniprot/Q64318 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. Binds to E-box sequences in the immunoglobulin heavy chain enhancer as well as in the regulatory regions of many other tissue-specific genes. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1 (By similarity). Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (PubMed:20713358). Promotes tumorigenicity by repressing stemness-inhibiting microRNAs (PubMed:19935649).|||Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family.|||Expressed in the external germinal layer (EGL) and internal granular layer (IGL) of the cerebellum (at protein level).|||Induced during Neurod2-induced neurogenesis.|||Interacts (via N-terminus) with SMARCA4/BRG1.|||Nucleus http://togogenome.org/gene/10090:Chrm2 ^@ http://purl.uniprot.org/uniprot/Q9ERZ4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily.|||Cell membrane|||Interacts with ARRB1 and ARRB2. Interacts with RACK1; the interaction regulates CHRM2 internalization (By similarity).|||Phosphorylated in response to agonist treatment.|||Postsynaptic cell membrane|||The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol (By similarity). http://togogenome.org/gene/10090:Cks2 ^@ http://purl.uniprot.org/uniprot/P56390|||http://purl.uniprot.org/uniprot/Q545R9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the CKS family.|||Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.|||Forms a homohexamer that can probably bind six kinase subunits. http://togogenome.org/gene/10090:Pnpla6 ^@ http://purl.uniprot.org/uniprot/A0A140LI54|||http://purl.uniprot.org/uniprot/Q3TRM4 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NTE family.|||Embryonically lethal. At 9 dpc, embryos are smaller, and their development is delayed (PubMed:12640454). At 10-11 dpc, the development is arrested with signs of resorption (PubMed:12640454). Heterozygous mice have lower catalytic activity towards the synthetic compound phenyl valerate in the brain and show increased motor activity (PubMed:12640454).|||Endoplasmic reticulum membrane|||Expressed in brain, testes and kidney (at protein level) (PubMed:12640454). Expressed ubiquitously in brain of young mice (PubMed:10640712). Reaching adulthood, there is a most prominent expression in Purkinje cells, granule cells and pyramidal neurons of the hippocampus and some large neurons in the medulla oblongata, nucleus dentatus and pons (PubMed:10640712).|||Expressed in the embryonic respiratory system, different epithelial structures and strongly in the spinal ganglia, during the development.|||Glycosylated.|||Inhibited by a series a OPs such as mipafox (MPX), phenyl saligenin phosphate (PSP), phenyl dipentyl phosphinate (PDPP), diisopropyl fluorophosphate and paraoxon.|||Membrane|||Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho) (PubMed:18086666) (Probable). This deacylation occurs at both sn-2 and sn-1 positions of PtdCho. Catalyzes the hydrolysis of several naturally occurring membrane-associated lipids. Hydrolyzes lysophospholipids and monoacylglycerols, preferring the 1-acyl to the 2-acyl isomer. Does not catalyze hydrolysis of di- or triacylglycerols or fatty acid amides (By similarity).|||Specific chemical modification by some organophosphorus (OP) compounds leads to distal axonopathy in humans and chicken (Probable). The effects of these compounds in mice appear to be less severe (Probable). Mice treated with 1 mg/kg/body weight of ethyl octylphosphonofluoridate (EOPF) have elevated motor activity in the long term (PubMed:12640454). Higher doses result in increased mortality (PubMed:12640454). http://togogenome.org/gene/10090:Il18r1 ^@ http://purl.uniprot.org/uniprot/Q61098 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the interleukin-1 receptor family.|||Forms a ternary complex with IL18 and IL18RAP (By similarity). Within this complex, IL18R1 is involved in ligand-binding and IL18RAP in signaling leading to NF-kappa-B and JNK activation (By similarity). Interacts with SLC12A3 in peritoneal macrophages; this interaction is increased by IL18 treatment (PubMed:26099046).|||Membrane|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.|||Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B. Involved in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells (By similarity). Contributes to IL18-induced cytokine production, either independently of SLC12A3, or as a complex with SLC12A3 (PubMed:26099046). http://togogenome.org/gene/10090:Gcnt3 ^@ http://purl.uniprot.org/uniprot/Q5JCT0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 14 family.|||Glycosyltransferase that can synthesize all known mucin beta 6 N-acetylglucosaminides. Mediates core 2 and core 4 O-glycan branching, 2 important steps in mucin-type biosynthesis. Has also I-branching enzyme activity by converting linear into branched poly-N-acetyllactosaminoglycans, leading to introduce the blood group I antigen during embryonic development.|||Golgi apparatus membrane|||N-glycosylated. http://togogenome.org/gene/10090:Pard3 ^@ http://purl.uniprot.org/uniprot/A5D6P2|||http://purl.uniprot.org/uniprot/B7ZNY3|||http://purl.uniprot.org/uniprot/E9PYJ2|||http://purl.uniprot.org/uniprot/G3XA13|||http://purl.uniprot.org/uniprot/Q99NH2 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated. Deacetylated by SIRT2, thereby inhibiting Schwann cell peripheral myelination.|||Adapter protein involved in asymmetrical cell division and cell polarization processes (By similarity). Seems to play a central role in the formation of epithelial tight junctions (By similarity). Targets the phosphatase PTEN to cell junctions (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (PubMed:11839275). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (By similarity). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Involved in Schwann cell peripheral myelination (PubMed:21949390).|||All isoforms are expressed in heart, while expression in brain is mainly limited to isoform 1, and to isoform 3 to a weaker level.|||Belongs to the PAR3 family.|||Cell junction|||Cell membrane|||Contains a conserved N-terminal oligomerization domain (NTD) that is involved in oligomerization and is essential for proper subapical membrane localization.|||Cytoplasm|||Endomembrane system|||Expressed at the outer limiting membrane of the retina at 3 months of age.|||Expressed in the oocyte from 9.5 dpc to 14.5 dpc.|||Expression decreases in the egg as compared to the oocyte.|||Expression increases steadily throughout oocyte maturation.|||Interacts with PRCKI and CDH5. Interacts (via PDZ 3 domain) with PTEN (via C-terminus). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with LIMK2, AURKA and AURKB. Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with ECT2 and FBF1 (By similarity). Interacts (via PDZ 1 domain) with F11R/JAM1, PARD6A and PARD6B. Part of a complex with PARD6A or PARD6B, PRKCI or PRKCZ and CDC42 or RAC1. Directly interacts with TIAM1 and TIAM2. Interacts with SIRT2. Interacts (via coiled-coil domain) with FRMD4A (PubMed:20080746). Found in a complex with PARD3, CYTH1 and FRMD4A (PubMed:20080746). Interacts with SAPCD2 (By similarity). Interacts with PRKCA (By similarity).|||Interacts with PRKCZ.|||Not expressed in the oocyte.|||Phosphorylation at Ser-824 by PRKCZ and PRKCI occurs at the most apical tip of epithelial cell-cell contacts during the initial phase of tight junction formation and may promote dissociation of the complex with PARD6. EGF-induced Tyr-1123 phosphorylation mediates dissociation from LIMK2 (By similarity). Phosphorylation by AURKA at Ser-958 is required for the normal establishment of neuronal polarity (By similarity). Isoform 4 and isoform 5 are phosphorylated during oocyte maturation (Probable).|||The second PDZ domain mediates interaction with membranes containing phosphoinositol lipids.|||adherens junction|||cell cortex|||cytoskeleton|||tight junction http://togogenome.org/gene/10090:Kifbp ^@ http://purl.uniprot.org/uniprot/Q6ZPU9 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the KIF-binding protein family.|||Contaminating sequence. Potential poly-A sequence.|||In the embryo it is expressed in cortical neurons; expression increases during neuronal development.|||Interacts with KIF1B. Interacts with STMN2.|||Required for neuronal development and differentiation. Required for organization of axonal microtubules, and axonal outgrowth and maintenance during peripheral and central nervous system development.|||cytoskeleton http://togogenome.org/gene/10090:Tomm6 ^@ http://purl.uniprot.org/uniprot/Q9CQN3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tom6 family.|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70).|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Prkci ^@ http://purl.uniprot.org/uniprot/Q5DTK3|||http://purl.uniprot.org/uniprot/Q62074 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-411 (activation loop of the kinase domain) and Thr-563 (turn motif), need to be phosphorylated for its full activation (By similarity). Might also be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI3K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis (By similarity). Downstream of PI3K is required for insulin-stimulated glucose transport. Activates RAB4A and promotes its association with KIF3A which is required for the insulin-induced SLC2A4/GLUT4 translocation in adipocytes. Is essential in early embryogenesis and development of differentiating photoreceptors by playing a role in the establishment of epithelial and neuronal polarity. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity).|||Cytoplasm|||Embryonic lethal at 9.5 dpc.|||Endosome|||Expressed apically in the cortical neuroepithelium along the ventricular surface at 14.5 dpc.|||Forms a complex with SQSTM1 and MP2K5 (PubMed:12813044). Interacts directly with SQSTM1 (Probable). Interacts with IKBKB. Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and a GTPase protein (CDC42 or RAC1) (PubMed:10934474). Part of a complex with LLGL1 and PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the ZN-finger domain, activates the kinase activity. Interacts with CDK7. Forms a complex with RAB2A and GAPDH involved in recruitment onto the membrane of vesicular tubular clusters (VTCs). Interacts with ECT2 ('Thr-359' phosphorylated form) (By similarity). Interacts with VAMP2 (PubMed:17313651). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).|||Membrane|||Nucleus|||Phosphorylation at Thr-411 in the activation loop is not mandatory for activation (PubMed:22579248). Upon neuronal growth factor (NGF) stimulation, phosphorylated by SRC at Tyr-264, Tyr-279 and Tyr-333 (By similarity). Phosphorylation on Tyr-264 facilitates binding to KPNB1/importin-beta regulating entry of PRKCI into the nucleus (By similarity). Phosphorylation on Tyr-333 is important for NF-kappa-B stimulation (By similarity). Phosphorylated at Thr-563 during the initial phase of long term potentiation (By similarity).|||The C1 zinc finger does not bind diacylglycerol (DAG).|||The PB1 domain mediates interaction with SQSTM1.|||The pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins, except the presence of a non-phosphorylatable residue in place of Ser, it modulates activity by competing with substrates. http://togogenome.org/gene/10090:Rchy1 ^@ http://purl.uniprot.org/uniprot/Q9CR50 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in testis, liver, kidney and heart.|||E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins, including p53/TP53, TP73, HDAC1 and CDKN1B (By similarity). Mediates ubiquitination and degradation of p53/TP53; preferentially acts on tetrameric p53/TP53 (By similarity). Catalyzes monoubiquitinates the translesion DNA polymerase POLH (PubMed:12654245). Involved in the ribosome-associated quality control (RQC) pathway, which mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes: RCHY1 acts downstream of NEMF and recognizes CAT tails associated with stalled nascent chains, leading to their ubiquitination and degradation (By similarity).|||Monomer and homodimer. Interacts with AR, MDM2, KAT5, PLAG1, PLAGL2, COPE, UBE2D2 and GORAB/NTKLBP1.|||Nucleus|||Nucleus speckle|||Subject to ubiquitination and proteasomal degradation. Interaction with PLAGL2 or KAT5 enhances protein stability.|||Up-regulated upon p53/TP53 activation. http://togogenome.org/gene/10090:Evl ^@ http://purl.uniprot.org/uniprot/E9PVP4|||http://purl.uniprot.org/uniprot/F8WJB9|||http://purl.uniprot.org/uniprot/P70429|||http://purl.uniprot.org/uniprot/Q6PB99 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At an early stage, highly expressed in the branchial and pharyngeal arches, but not in the brain. Expression in the brain starts at 15 dpc (at protein level).|||Belongs to the Ena/VASP family.|||Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. EVL enhances actin nucleation and polymerization.|||Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration.|||Highest expression in thymus and spleen (at protein level). Low levels in placenta, ovary, testis, fat and lung (at protein level). Isoform 1 and isoform 2 are expressed in cortical neurons and glial cells.|||Homotetramer (By similarity). Binds to the SH3 domains of ABL1, LYN and SRC (PubMed:10945997). Also binds to profilin, with preference for isoform IIa of PFN2, and the WW domain of APBB1/FE65 (PubMed:10945997). Binds to SEMA6A (PubMed:10993894). Interacts, via the Pro-rich region, with the C-terminal SH3 domain of DNMBP (PubMed:14506234). Interacts with RAPH1 (By similarity). Binds, via the EVH1 domain, the Pro-rich domain of Listeria monocytogenes actA (PubMed:10087267). Binds, via the EVH1 domain, the Pro-rich domain of ZYX. Interacts with FYB1. Interacts with ZDHHC17 (By similarity).|||Phosphorylated by PKA; phosphorylation abolishes binding to SH3 domains of ABL and SRC.|||Required to transform actin polymerization into active movement for the propulsive force of Listeria monocytogenes.|||The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.|||cytoskeleton|||lamellipodium|||stress fiber http://togogenome.org/gene/10090:Coro2b ^@ http://purl.uniprot.org/uniprot/Q8BH44 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat coronin family.|||Binds to F-actin and to vinculin.|||May play a role in the reorganization of neuronal actin structure.|||cytoskeleton http://togogenome.org/gene/10090:Gbp4 ^@ http://purl.uniprot.org/uniprot/A4UUI3 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Cytoplasm|||Golgi apparatus membrane|||Heterodimer with other family members, including GBP1, GBP2 and GBP5 (By similarity). Dimerization regulates subcellular location (By similarity). Interacts with IRF7; preventing interaction between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination (PubMed:22095711).|||Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:18025219). Negatively regulates the antiviral response by inhibiting activation of IRF7 transcription factor (PubMed:22095711).|||Mainly expressed in organs of the immune system, such as spleen and lymph nodes.|||Nucleus|||Up-regulated in response to Sendai virus (SeV) infection.|||perinuclear region http://togogenome.org/gene/10090:Utp25 ^@ http://purl.uniprot.org/uniprot/A0A0R4J114|||http://purl.uniprot.org/uniprot/Q8BTT6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UTP25 family.|||Component of the ribosomal small subunit processome for the biogenesis of ribosomes, functions in pre-ribosomal RNA (pre-rRNA) processing (By similarity). Essential for embryonic development in part through the regulation of p53 pathway. Controls the expansion growth of digestive organs and liver (PubMed:29262616, PubMed:32303961). Also involved in the sympathetic neuronal development (By similarity). Mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 (By similarity).|||Expressed in all tissues tested: brain, small intestine, large intestine, stomach, liver, spleen, thymus, lung, kidney and testes (at protein level).|||Interacts with CAPN3; the interaction is required for CAPN3 translocation to the nucleolus.|||Mutant embryos are peri-implantation lethal at E4.5-E5.5 stages (PubMed:29262616, PubMed:32303961). Conditional knockouts in hepatocytes do not show overall differences in liver growth but suffer from liver chronic inflammation (PubMed:32303961). Hepatocytes show nuclei enlargement with nuclear vacuolization (PubMed:32303961). Animals have bile duct hyperplasia and polycystic liver (PubMed:32303961). Males die suddenly after hepatectomy due to overactive inflammatory response (PubMed:32303961).|||Phosphorylated. Phosphorylation is required to promote p53/TP53 degradation in the nucleolus which promotes cell cycle progression and liver development.|||nucleolus http://togogenome.org/gene/10090:Atg16l1 ^@ http://purl.uniprot.org/uniprot/G9M4M6|||http://purl.uniprot.org/uniprot/Q3TDQ5|||http://purl.uniprot.org/uniprot/Q8C0J2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat ATG16 family.|||Cytoplasm|||Endosome membrane|||Expressed in brain.|||Expressed in liver.|||Highly expressed in liver.|||Homodimer (By similarity). Homooligomer (PubMed:12665549). Heterooligomer with ATG16L2 (PubMed:22082872). Interacts with WIPI1 (By similarity). Interacts with WIPI2 (PubMed:24954904). Interacts with RB1CC1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:23392225, PubMed:23262492). Interacts with ATG5 (PubMed:12665549). Part of either the minor and major complexes respectively composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and ATG16L1 (800 kDa). Interacts with RAB33B (PubMed:18448665). Interacts (via WD repeats) with TMEM59; the interaction mediates unconventional autophagic activity of TMEM59 (By similarity). Interacts with TLR2 (By similarity). Interacts (via WD repeats) with MEFV (By similarity). Interacts (via N-terminal) with CLTC (By similarity). Interacts with NOD1 (PubMed:19898471). Interacts with NOD2 (PubMed:19898471, PubMed:19966812). Interacts with TUFM (By similarity). Interacts with TRIM16 (By similarity). Interacts (via WD repeats) with SPATA33 (PubMed:33087875). Interacts with Irgm1 (By similarity).|||Lysosome membrane|||Phosphorylation at Ser-139 promotes association with the ATG12-ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex.|||Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP) (PubMed:12665549, PubMed:18849966, PubMed:19898471, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:33586810). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non-canonical signaling (PubMed:33586810). During canonical autophagy, interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to produce a membrane-bound activated form of ATG8 (By similarity). Thereby, controls the elongation of the nascent autophagosomal membrane (By similarity). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, probably by catalyzing conjugation of phosphatidylserine (PS) to ATG8 (By similarity). Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus (PubMed:33586810). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (By similarity). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response (PubMed:24238340). Instead, promotes an autophagy-dependent antibacterial pathway together with NOD1 or NOD2 (PubMed:19898471, PubMed:19966812, PubMed:24238340). Plays a role in regulating morphology and function of Paneth cell (By similarity).|||Preautophagosomal structure membrane|||Proteolytic cleavage by activated CASP3 leads to degradation and may regulate autophagy upon cellular stress and apoptotic stimuli.|||The WD repeats are required for non-canonical autophagy but not for canonical autophagy.|||Widely expressed (PubMed:12665549). Expressed in the testis and sperm midpiece (at protein level) (PubMed:33087875). http://togogenome.org/gene/10090:Or8k20 ^@ http://purl.uniprot.org/uniprot/Q7TR76 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbfox3 ^@ http://purl.uniprot.org/uniprot/Q8BIF2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ By retinoic acid. Expression is up-regulated in P19 cells during neural differentiation upon retinoic acid treatment (at the protein level).|||Cytoplasm|||In the neural tube, expressed as early as 9.5 dpc and expression is confined to the nervous system. By 12.5 dpc, can be found in the developing ventral horns and is also detected in the developing dorsal horns as well as in the dorsal root ganglion. Not detected in the ventricular zone, roof plate, floor plate or marginal zone (developing white matter). It is expressed from embryonic stage to adulthood.|||Initial characterization was derived from usage of a monoclonal antibody (A60) directed to an unknown protein called NeuN (PubMed:15605376, PubMed:1483388), but later identified as RBFOX3.|||Knockout mice have significantly reduced brain weight, impaired neurofilament expression and decreased white matter volume, but normal total body mass. They show increased susceptibility to seizures and reduced anxiety-related behaviors compared with wild type littermates, as well as defective hippocampal gene expression and deficits in synaptic transmission and plasticity in the dentate gyrus.|||Nucleus|||Phosphorylated.|||Pre-mRNA alternative splicing regulator. Regulates alternative splicing of RBFOX2 to enhance the production of mRNA species that are targeted for nonsense-mediated decay (NMD).|||Widely expressed in brain, including in cerebral cortex, hippocampus, thalamus, caudate/putamen, cerebellum, as well as in the spinal cord (at protein level). Not expressed in all neuronal cells within a region, in cerebellum, expression is absent in Purkinje cells (at protein level). Expressed in the retina in the ganglion cells and some cells in the inner nuclear layer, but absent from the photoreceptor cells and most cells in the inner nuclear layer (at protein level). http://togogenome.org/gene/10090:Gabarapl2 ^@ http://purl.uniprot.org/uniprot/P60521 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATG8 family.|||Endoplasmic reticulum membrane|||Golgi apparatus|||Monomer (By similarity). Interacts with ATG3, ATG13 and ULK1 (By similarity). Interacts with ATG7 (PubMed:11890701). Interacts with TP53INP1 and TP53INP2 (By similarity). Interacts with TBC1D25 (PubMed:21383079). Directly interacts with SQSTM1 and BNIP3 (By similarity). Interacts with TECPR2 and PCM1 (By similarity). Interacts with TBC1D5 (By similarity). Interacts with TRIM5 (By similarity). Interacts with MEFV and TRIM21 (By similarity). Interacts with WDFY3 (By similarity). Interacts with UBA5; promoting recruitment of UBA5 to the endoplasmic reticulum membrane (By similarity). Interacts with GOSR1 (By similarity). Interacts with KBTBD6 and KBTBD7; the interaction is direct (By similarity). Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3 (PubMed:34338405). Interacts with Irgm1 (By similarity).|||Phosphorylation at Ser-87 and Ser-88 by TBK1 prevents interaction with ATG4 (ATG4A, ATG4B, ATG4C or ATG4D). Phosphorylation by TBK1 on autophagosomes prevents their delipidation by ATG4 and premature removal from nascent autophagosomes.|||The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, GABARAPL2-I (PubMed:14530254). The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, GABARAPL2-II (By similarity). During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid (By similarity). ATG4 proteins also mediate the delipidation of PE-conjugated forms required for GABARAPL2 recycling when autophagosomes fuse with lysosomes (PubMed:33795848). In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy (By similarity). ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (PubMed:33795848).|||Ubiquitin-like modifier involved in intra-Golgi traffic. Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation. It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy. Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (By similarity).|||Ubiquitous. A high level expression is seen in brain, thymus, lung, heart, liver and kidney.|||autophagosome http://togogenome.org/gene/10090:Pwwp4a ^@ http://purl.uniprot.org/uniprot/Q52KH6 ^@ Similarity ^@ Belongs to the PWWP3A family. http://togogenome.org/gene/10090:Adam8 ^@ http://purl.uniprot.org/uniprot/Q05910|||http://purl.uniprot.org/uniprot/Q3U1J7|||http://purl.uniprot.org/uniprot/Q3U7G2 ^@ Caution|||Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Interacts with FST3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Macrophages.|||Membrane|||Possible involvement in extravasation of leukocytes. http://togogenome.org/gene/10090:Or4a78 ^@ http://purl.uniprot.org/uniprot/Q7TQZ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxl7 ^@ http://purl.uniprot.org/uniprot/Q5BJ29 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FBXL7 family.|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7 (PubMed:22306998). Interacts with AURKA; interaction takes place during mitosis but not in interphase (PubMed:22306998). Interacts with BIRC5; this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7) E3 ubiquitin-protein ligase complex (PubMed:25778398).|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:22306998, PubMed:25778398). During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest (PubMed:22306998). It also regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5 (PubMed:25778398).|||centrosome http://togogenome.org/gene/10090:Ccdc92 ^@ http://purl.uniprot.org/uniprot/Q8VDN4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CEP164.|||Interferon-stimulated protein that plays a role in innate immunity.|||Phosphorylated at Ser-192 by TTBK2.|||centriole http://togogenome.org/gene/10090:Dmrt2 ^@ http://purl.uniprot.org/uniprot/Q8BG36 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DMRT family.|||Expressed in presomitic mesoderm and developing somites at 8.5 dpc, accumulating in the epaxial domain at 9.5 dpc in the immature caudal somites. At 10.5 dpc expressed in the dermomyotome of somites. By 11.5 dpc, only detectable in caudal somites. In mature somites, expression is confined to the dermomyotome of the somite where Pax3 is also expressed and in the epaxial domain of the most immature caudal somites. At this stage, the most mature anterior somites are beginning to lose the expression at the epaxial and hypaxial extremities of the dermomyotome. At 14.5 dpc expressed in testis, heart and brain. Expression is also detected in proximal forelimb buds and branchial arches of the developing embryo.|||Expressed in testis.|||Homodimer.|||Mice heterozygous for Dmrt2 mutation exhibit no visible phenotype. Homozygotes are perinatally lethal due to signs of respiratory distress. They have rib, sternal, vertebral and skull base malformations. Expression of myogenic growth factors, such as Pax3 and Myog, the growth factor Pdgfa, cadherin Cdh2, and the filament protein Des is abnormal. Mutants lack most or all of the epithelial organization seen in wild-type somites, sclerotome and dermomyotome. Mutants have disrupted production of matrix components including laminin-1 in the dermomyotome. Arrangement of the myogenic cells of the inter-limb somites is abnormal. Myf5 activation in the epaxial domain is retarded thus having consequences in the myogenesis by delaying expression of Myog. Mutants do not have left-right defects regarding internal organs positioning. Dmrt2 and Pax3 double null mutant embryos exhibit suspended development and Myog expression is markedly decreased and its expression pattern dramatically distorted.|||Nucleus|||Transcriptional activator that directly regulates early activation of the myogenic determination gene MYF5 by binding in a sequence-specific manner to the early epaxial enhancer element of it. Involved in somitogenesis during embryogenesis and somite development and differentiation into sclerotome and dermomyotome. Required for the initiation and/or maintenance of proper organization of the sclerotome, dermomyotome and myotome. Is not required for sex determination and/or differentiation in embryonic development. Also not involved in symmetric somite formation and hence does not regulate the laterality pathway that controls left-right asymmetric organ positioning.|||Transcriptionally up-regulated by PAX3 within the dermomyotome. http://togogenome.org/gene/10090:Or4k44 ^@ http://purl.uniprot.org/uniprot/Q8VGE5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tm4sf4 ^@ http://purl.uniprot.org/uniprot/Q3TMT3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the L6 tetraspanin family.|||Membrane http://togogenome.org/gene/10090:Rassf6 ^@ http://purl.uniprot.org/uniprot/Q80UQ2 ^@ Function|||Sequence Caution|||Subunit ^@ Interacts with MOAP1. Interaction with activated KRAS is still a matter of debate: interaction has been shown in the mouse (PubMed:17404571), but not in human (PubMed:17367779). Lack of interaction with MRAS, NRAS nor RRAS2 has also been reported (PubMed:17367779).|||Involved in the induction of apoptosis. May act as a Ras effector protein. May suppress the serum-induced basal levels of NF-kappa-B.|||Probable cloning artifact. Contains an insertion not found in the reference genome. http://togogenome.org/gene/10090:Cyp4f13 ^@ http://purl.uniprot.org/uniprot/Q99N19 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Ltc4s ^@ http://purl.uniprot.org/uniprot/Q60860|||http://purl.uniprot.org/uniprot/Q8K355 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAPEG family.|||Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4 with high specificity (PubMed:8706658, PubMed:11319240). Can also catalyze the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions (By similarity).|||Deficient mice developed normally and are fertile. However mice display abnormal inflammatory and hypersensitivity reactions.|||Endoplasmic reticulum membrane|||Homotrimer. Interacts with ALOX5AP and ALOX5.|||Inhibited by MK886.|||Membrane|||Nucleus membrane|||Nucleus outer membrane|||Phosphorylation at Ser-36 by RPS6KB1 inhibits the leukotriene-C4 synthase activity.|||Widely expressed. http://togogenome.org/gene/10090:Sv2b ^@ http://purl.uniprot.org/uniprot/Q8BG39 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with C.botulinum neurotoxin type A (BoNT/A, botA).|||(Microbial infection) Interacts with C.botulinum neurotoxin type D (BoNT/D, botD) (PubMed:21483489). No evidence for its interaction with BoNT/D has also been published (PubMed:21632541).|||(Microbial infection) Possible receptor for C.botulinum neurotoxin type D (BoNT/D, botD) (PubMed:21483489). Not a receptor for C.botulinum neurotoxin type D (BoNT/D, botD) (PubMed:21632541).|||(Microbial infection) Receptor for C.botulinum neurotoxin type A (BoNT/A, botA); the toxin probably binds via extracellular loop 4 (PubMed:16543415).|||(Microbial infection) Receptor for C.botulinum neurotoxin type E (BoNT/E); the toxin probably binds via extracellular loop 4 (PubMed:18815274). It probably requires glycosylation of Asn-516 (PubMed:18815274).|||Belongs to the major facilitator superfamily.|||Expressed during synaptogenesis in the retina (at protein level).|||Expressed in ribbon synapses of the retina (at protein level) (PubMed:12687700). Expressed in diaphragm motor nerve terminals (at protein level) (PubMed:16543415). Expressed in hippocampus neurons (at protein level) (PubMed:18815274).|||Interacts with SYT1 in a calcium-independent manner. Forms a complex with SYT1, syntaxin-1 and SNAP25.|||Mice display no particular phenotype (PubMed:10624962). Single knockout mice survive significantly longer than wild-type mice upon exposure to C.botulinum neurotoxin type A (BoNT/A, botA) (PubMed:16543415). Mice lacking both Sv2a and Sv2b experience severe epileptic seizures and die immediately or shortly after birth similarly to mice lacking only Sv2a (PubMed:10624962). Single knockout mice bind reduced amounts of BoNT/A than wild-type mice (PubMed:16543415). Single knockout mice are significantly more resistant to C.botulinum neurotoxin type E (BoNT/E) than wild-type mice (PubMed:18815274). In single knockout mice, synaptobrevin (VAMP, the target of C.botulinum neurotoxin type D, BoNT/D) is degraded by BoNT/D, and hippocampal neurons bind BoNT/D (PubMed:21483489). Hippocampal neurons from young mice lacking both Sv2a and Sv2b do not bind BoNT/A, nor do they take it up (PubMed:16543415, PubMed:18815274). Hippocampal neurons from young mice lacking both Sv2a and Sv2b do not bind C.botulinum neurotoxin type E (BoNT/E), nor do they take it up (PubMed:18815274). Hippocampal neurons from young mice lacking both Sv2a and Sv2b do not bind C.botulinum neurotoxin type D (BoNT/D, botD), nor do they take it up (PubMed:21483489). Hippocampal neurons from young mice lacking both Sv2a and Sv2b take up C.botulinum neurotoxin type C (BoNT/C) and C.botulinum neurotoxin type F (BonT/F, botF) normally (PubMed:21483489).|||N-glycosylated.|||Probably plays a role in the control of regulated secretion in neural and endocrine cells.|||The N-terminal cytoplasmic domain is phosphorylated by CK1.|||The use of this protein as a coreceptor for C.botulinum type D (BoNT/D, botD) is controversial. In double SV2A/SV2B knockout mice BoNT/D does not degrade its synaptobrevin target; introducing SV2A, SV2B or SV2C restores target cleavage (PubMed:21483489). However another group does not find a convincing interaction with SV2 (PubMed:21632541).|||Up-regulated upon Sv2a depletion.|||acrosome|||synaptic vesicle membrane http://togogenome.org/gene/10090:Vmn1r209 ^@ http://purl.uniprot.org/uniprot/Q5NC97 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc25a44 ^@ http://purl.uniprot.org/uniprot/Q3TMC4|||http://purl.uniprot.org/uniprot/Q3TNN4|||http://purl.uniprot.org/uniprot/Q8BGF9 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Expression increases during adipogenesis.|||Highly expressed in brown adipose tissues compared with other metabolic organs.|||Induction by cold exposure in brown adipose tissues.|||Membrane|||Mitochondrial solute transporter which transports branched-chain amino acid (BCAA; valine, leucine and isoleucine) into mitochondria in brown adipose tissue (BAT) (PubMed:31435015). BAT is involved in BCAA catabolism and actively utilizes BCAA in the mitochondria for thermogenesis (PubMed:31435015).|||Mitochondrion membrane http://togogenome.org/gene/10090:Ush2a ^@ http://purl.uniprot.org/uniprot/Q2QI47 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with collagen IV and fibronectin via its laminin EGF-like domains. Interaction with collagen may be required for stable integration into the basement membrane. Interacts with NINL (By similarity). Interacts with USH1C (PubMed:16301217). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN (PubMed:20502675, PubMed:25406310). Interacts with ADGRV1/MASS1 (via N-terminal PDZ domain) (PubMed:20502675). Interacts (via the cytoplasmic region) with WHRN (PubMed:16301217, PubMed:20502675, PubMed:23055499). Interacts (via the cytoplasmic region) with PDZD7 (PubMed:23055499). Interacts (via the cytoplasmic region) with VEZT and MYO7A (via MyTH4-FERM domains); the interaction associates VEZT with the USH2 complex at the stereocilia base (PubMed:17567809).|||Involved in hearing and vision as member of the USH2 complex (PubMed:20502675). In the inner ear, required for the maintenance of hair bundle ankle formation, which connects growing stereocilia in developing cochlear hair cells (PubMed:20502675, PubMed:24334608). In retina photoreceptors, the USH2 complex is required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport (PubMed:20502675).|||Photoreceptor inner segment|||Present in the testis, epididymis, oviduct, spleen, submaxillary gland, and small and large intestines. Not detected in the brain, skin, lung, skeletal muscle, cardiac muscle, liver or kidney. Expressed in smooth muscle of the colon and the epididymis. Also present in select vascular basement membranes. In the cochlea, it is present in virtually every basement membrane. It is particularly high in the strial capillary basement membranes (SCBMs). In the retina, it is again expressed in all of the basement membranes. It is also very prevalent in the lens capsule and the Bruch's layer between the retinal pigment epithelium and the choroid layer, which is very rich in basement membranes. In neonates in it is widely expressed in the basement membranes of the cochlea. Present in the synaptic terminals of retinal photoreceptors (at protein level).|||Secreted|||The PDZ-binding motif mediates the association with some of the PDZ domains of USH1C and WHRN.|||stereocilium membrane http://togogenome.org/gene/10090:Polr3k ^@ http://purl.uniprot.org/uniprot/Q9CQZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF-kappa-B through the RIG-I pathway (By similarity).|||nucleolus http://togogenome.org/gene/10090:Ptar1 ^@ http://purl.uniprot.org/uniprot/A0A494B9V8 ^@ Similarity ^@ Belongs to the protein prenyltransferase subunit alpha family. http://togogenome.org/gene/10090:Best2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0P0|||http://purl.uniprot.org/uniprot/Q8BGM5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.|||Cell membrane|||Forms calcium-sensitive chloride channels. Permeable to bicarbonate.|||Mainly confined to the retinal pigment epithelium and colon.|||Membrane http://togogenome.org/gene/10090:Cabp4 ^@ http://purl.uniprot.org/uniprot/Q8VHC5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in retina and in the inner hair cells (IHC) of the cochlea.|||Interacts with CACNA1F and CACNA1D (via IQ domain) in a calcium independent manner. Interacts (via N-terminus) with UNC119.|||Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission. Modulator of CACNA1D and CACNA1F, suppressing the calcium-dependent inactivation and shifting the activation range to more hyperpolarized voltages.|||Phosphorylated. Phosphorylation levels change with the light conditions and regulate the activity, but has no effect on calcium binding.|||Presynapse http://togogenome.org/gene/10090:Lgi2 ^@ http://purl.uniprot.org/uniprot/Q50DZ7|||http://purl.uniprot.org/uniprot/Q8K4Z0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Brain.|||Expressed in developing parvalbumin-positive basket cells.|||Required for the development of soma-targeting inhibitory GABAergic synapses made by parvalbumin-positive basket cells.|||Secreted http://togogenome.org/gene/10090:Tlr13 ^@ http://purl.uniprot.org/uniprot/Q6R5N8 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Toll-like receptor family.|||Binds MYD88 via their respective TIR domains (By similarity). Interacts with UNC93B1.|||Component of innate and adaptive immunity that recognizes and binds 23S rRNA from bacteria. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Specifically binds the 5'-CGGAAAGACC-3' sequence on bacterial 23S rRNA, a sequence also bound by MLS group antibiotics (including erythromycin). May also recognize vesicular stomatitis virus; however, these data require additional evidences.|||Endosome membrane|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||The sequence 23S rRNA from clinical isolates of erythromycin-resistant S.aureus is methylated and is not recognized by Tlr13 anymore, suggesting a link between antibiotic resistance and evasion from Tlr13 recognition. 23S rRNA modifications generating resistance toward MLS antibiotics preventing recognition of bacteria from Tlr13. These data may also explain why Tlr13 is not conserved in human: human may instead possess a related rRNA-sensing pattern recognition receptor that has evolved to recognize species that can hide from Tlr13 owing to rRNA modifications (PubMed:22821982). http://togogenome.org/gene/10090:Map3k7cl ^@ http://purl.uniprot.org/uniprot/P58500 ^@ Domain|||Tissue Specificity ^@ Contains a C-terminal domain similar to that of the C-terminal section of MAP3K7.|||Ubiquitous. http://togogenome.org/gene/10090:Unkl ^@ http://purl.uniprot.org/uniprot/Q5FWH2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although this protein contains a RING domain, intrinsic E3 ligase activity has not been proven.|||Belongs to the unkempt family.|||Cytoplasm|||Interacts with the GTP-bound form of Rac1. Interacts with Baf60b/Smarcd2 (By similarity).|||May participate in a protein complex showing an E3 ligase activity regulated by Rac1. Ubiquitination is directed towards itself and possibly other substrates, such as Baf60b/Smarcd2. Intrinsic E3 ligase activity has not been proven.|||Nucleus|||Ubiquitination is enhanced by activated Rac1. The presence of the RING finger domain is not essential for ubiquitination to occur (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Cox7a2 ^@ http://purl.uniprot.org/uniprot/P48771 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIIa family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)). Interacts with PET100.|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Mpeg1 ^@ http://purl.uniprot.org/uniprot/A1L314|||http://purl.uniprot.org/uniprot/E9QN37 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MPEG1 family.|||By CSF1 in fetal liver macrophages (PubMed:7888681). By interferon-alpha, by interferon-beta, by interferon-gamma and by bacterial infection with E.coli and M.smegmatis in embryonic fibroblasts (PubMed:23257510).|||Cytoplasmic vesicle membrane|||Expressed constitutively in a variety of cell types including macrophages, microglia, neutrophils, T cells, marginal zone B cells, keratinocytes, splenocytes and intestinal epithelial cells.|||Forms arc- and ring-shaped pre-pores on top of the membrane at neutral to slightly acidic pH conditions and converts to pores upon acidification (PubMed:36028507, PubMed:32064340, PubMed:36245269). Undergoes transition from the pre-pore to the pore in a processive clockwise hand-over-hand process (PubMed:36028507, PubMed:32064340, PubMed:36245269). In the pore state, 2 alpha-helical regions refold into transmembrane hairpins (TMH1 and TMH2) in each protomer that form in the ensemble complex giant beta-barrel transmembrane pores (PubMed:36028507, PubMed:32064340, PubMed:36245269).|||Homooligomer; predominantly forms a homooligomeric arc-shaped pore complex instead of complete rings of 16 subunits.|||Impaired immunity characterized by a failure to efficiently prime CD8(+) T-cells to cell-associated antigens (PubMed:37347855). Defects are caused by impaired cross-presentation of cell-associated antigens (PubMed:37347855). In normal conditions, mice do not show any obvious disease phenotype or a change in immune cell frequencies (PubMed:37347855).|||Membrane|||Monoubiquitinated in response to bacterial infection; ubiquitination is required for vesicular localization and antibacterial activity and can be blocked by bacterial cell cycle inhibiting factor (cif) (PubMed:26418746).|||Pore-forming protein involved in both innate and adaptive immunity (PubMed:26402460, PubMed:30249808, PubMed:36028507, PubMed:37347855, PubMed:32064340, PubMed:36245269). Plays a central role in antigen cross-presentation in dendritic cells by forming a pore in antigen-containing compartments, thereby promoting delivery of antigens for cross-presentation (PubMed:35471730, PubMed:37347855). Also involved in innate immune response following bacterial infection; shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria (PubMed:23257510, PubMed:23753625, PubMed:26402460). Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol (PubMed:26831467). Required for the antibacterial activity of reactive oxygen species and nitric oxide (PubMed:26402460).|||Pore-forming protein that plays a central role in antigen cross-presentation in dendritic cells by mediating delivery of antigens for cross-presentation (PubMed:37347855). Dendritic cells bridge innate and adaptive immunity by capturing exogenous antigens on MHC class-I molecules and presenting them to naive CD8(+) T-cells (PubMed:37347855). Acts by forming a pore in antigen-containing compartments, promoting the release of antigens into the cytosol, enabling generation of MHCI:peptide complexes and T-cell priming (PubMed:37347855).|||Proteolytically processed in two steps to generate the Macrophage-expressed gene 1 protein, processed form: cleaved by trypsin in proximity of the helical transmembrane domain releases the ectodomain into the lysosomal lumen to orient the pore-forming domain toward the endogenous membranes, and processed by the asparagine endopeptidase (LGMN) (PubMed:37347855). Proteolytic processing in antigen-containing vesicles is pH-dependent (PubMed:37347855).|||The MACPF domain includes the central machinery of pore formation: acidification causes a significant structural rearrangement, leading to oligomerization and deployment of the transmembrane beta-strands (named TMH1 and TMH2) that enter the membrane as amphipathic beta-hairpins.|||The P2 region contains beta-hairpins to interact with target membranes.|||Was initially thought to facilitate killing of intravacuolar bacteria by inserting into the bacterial surface to form pores, thereby breaching the surface of phagocytosed bacteria (PubMed:30249808). These results were however not replicated in a later study (PubMed:35471730).|||phagosome membrane http://togogenome.org/gene/10090:Morn2 ^@ http://purl.uniprot.org/uniprot/Q6UL01 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected from postnatal day 15 onwards, with high levels of expression by postnatal day 28.|||Expressed strongly in testis, where it is specifically detected in haploid germ cells (at protein level). Also expressed strongly in skeletal muscle.|||Might have a role in spermatogenesis.|||Nucleus|||acrosome http://togogenome.org/gene/10090:Prx ^@ http://purl.uniprot.org/uniprot/O55103 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the periaxin family.|||Cell junction|||Cell membrane|||Cytoplasm|||Detected in embryonic eye lens; levels increase steadily from 10.5 dpc onto birth and continue to increase during the first three weeks after birth.|||Detected in myelinating Schwann cells in intramuscular nerves in triangularis sterni (PubMed:18205176). Detected in sciatic nerve (PubMed:11430802). Detected in eye lens fiber cells (PubMed:21745462). Isoform 1 is detected in myelinating Schwann cells in sciatic nerve (PubMed:9488714, PubMed:10671475, PubMed:10839370). Isoform 2 is detected in myelinating Schwann cells in sciatic nerve (at protein level) (PubMed:9488714, PubMed:10839370). Detected in sciatic nerve (PubMed:9488714, PubMed:10839370).|||Has a remarkable domain of repetitive pentameric units sometimes followed by a tripeptide spacer, it may separate two functional basic and acidic domains.|||Homodimer (via PDZ domain) (By similarity). Interacts with SCN10A. Found in a complex with SCN10A (By similarity). Interacts with DRP2 (PubMed:22764250). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (PubMed:11430802). Detected in a complex composed of at least EZR, AHNAK, PPL and PRX (By similarity). Identified in a complex with EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, VIM and spectrin (PubMed:21745462).|||Mice are born at the expected Mendelian rate and appear grossly normal during the first six weeks of life. After six to nine months, they display pronounced unsteadiness of gait and difficulty in supporting themselves on their hindlimbs, weight loss due to an inability to feed and labored respiration (PubMed:10839370). Their sensory, motor and vagus nerves show extensive demyelination with demyelinated segments surrounded by focal thickenings (PubMed:10839370, PubMed:18205176). In contrast, the predominantly sensory saphenous nerves are extensively hypermyelinated, resulting in myelin sheath infolding and axon compression (PubMed:10839370). At eight months, naked or thinly myelinated axons are common in sciatic nerve fibers (PubMed:10839370). Already at six weeks, mutant mice display markedly increased sensitivity to noxious mechanical and thermal stimuli (PubMed:10839370). Besides, four month old mutant mice display impaired remyelination after crush injury (PubMed:10839370). Schwann cells from mutant mice display a reduced rate of elongation, leading to decreased distances between nodes of Ranvier and reduced velocity of the transmission of nerve impulses; this results in impaired motor skills on the RotaRod in three week old mice (PubMed:15356632). Peripheral nerves show decreased conduction velocity, due to defects in the myelin sheath (PubMed:10839370). Motor axons from five month old mice show an increased number of preterminal branches that arise from demyelinated regions close to the neuromuscular junction (PubMed:18205176). In contrast, axon branching close to the neuromuscular junction appears normal in three week old mice (PubMed:18205176). At the molecular level, gene disruption impairs formation of Cajal bands and location of Drp2 in patches that colocalize with appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane (PubMed:15356632). Cytoplasm from mutant Schwann cells forms a concentric ring under the cell membrane, instead of being strictly compartmentalized at Cajal bands (PubMed:15356632). The transport of the mRNA coding for Mbp is impaired; the mRNA level is highest in the perinuclear region and does not accumulate in the paranodal region (PubMed:15356632). Eye lenses from 90 day old mutant mice appear grossly normal at the macroscopic level, but display altered shape and organization of inner lens fiber cells, together with alteration in the membrane localization of Mip, Ezr and Ahnak (PubMed:21745462).|||Nucleus|||Scaffolding protein that functions as part of a dystroglycan complex in Schwann cells, and as part of EZR and AHNAK-containing complexes in eye lens fiber cells (PubMed:11430802, PubMed:21745462, PubMed:22764250). Required for the maintenance of the peripheral myelin sheath that is essential for normal transmission of nerve impulses and normal perception of sensory stimuli (PubMed:10839370). Required for normal transport of MBP mRNA from the perinuclear to the paranodal regions (PubMed:15356632). Required for normal remyelination after nerve injury (PubMed:10839370). Required for normal elongation of Schwann cells and normal length of the internodes between the nodes of Ranvier. The demyelinated nodes of Ranvier permit saltatory transmission of nerve impulses; shorter internodes cause slower transmission of nerve impulses (PubMed:15356632, PubMed:23022068). Required for the formation of appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane; the Schwann cell cytoplasm is restricted to regions between these appositions (PubMed:15356632, PubMed:23022068). Required for the formation of Cajal bands and of Schmidt-Lanterman incisures that correspond to short, cytoplasm-filled regions on myelinated nerves (PubMed:23022068, PubMed:22764250). Recruits DRP2 to the Schwann cell plasma membrane (PubMed:11430802, PubMed:23022068, PubMed:22764250). Required for normal protein composition of the eye lens fiber cell plasma membrane and normal eye lens fiber cell morphology (PubMed:21745462).|||The Arg/Lys-rich basic domain functions as a tripartite nuclear localization signal.|||The PDZ domain contains the signal for export from the nucleus (By similarity). The N-terminal region including the PDZ domain is required for the formation of Cajal bands on myelinated nerves. http://togogenome.org/gene/10090:Ccnh ^@ http://purl.uniprot.org/uniprot/E9PWD3|||http://purl.uniprot.org/uniprot/Q61458 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates primarily with CDK7 and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.|||Belongs to the cyclin family. Cyclin C subfamily.|||Expressed in both the germinal and somatic cells of the testis.|||Higher expression during spermatogenesis from the mitotic stages to the meiotic stages.|||Nucleus|||Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle. http://togogenome.org/gene/10090:Gcfc2 ^@ http://purl.uniprot.org/uniprot/Q8BKT3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GCF family.|||Found in the Intron Large (IL) complex, a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors (By similarity). Interacts with TFIP11 and DHX15 (By similarity).|||Involved in pre-mRNA splicing through regulating spliceosome C complex formation (By similarity). May play a role during late-stage splicing events and turnover of excised introns (By similarity).|||Was originally thought to be a DNA-binding transcriptional repressor (By similarity). However, later work showed that the original sequence was a chimera and that the DNA-binding activity was derived from the incorrect N-terminal sequence (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Mapkapk5 ^@ http://purl.uniprot.org/uniprot/O54992 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated following phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11, ERK2/MAPK1, ERK3/MAPK6, and ERK4/MAPK4. Activated by stress-related extracellular stimuli; such as H(2)O(2), arsenite, anisomycin TNF alpha and also PMA and the calcium ionophore A23187; but to a lesser extent. In vitro, activated by SQSTM1. Inhibited by diterpenoid alkaloid noroxoaconitine.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Expressed ubiquitously.|||Interacts with SQSTM1 (By similarity). Interacts with ERK3/MAPK6 and ERK4/MAPK4 (via FRIEDE motif); the interaction is direct. Interacts with YWHAE; the interaction prevents phosphorylation of HSP27/HSPB1 leading to disrupt F-actin polymerization.|||Nucleus|||Phenotypes are different depending on reports. According to a first report, mice are viable and fertile and do not show changes in tissue morphology and behavior: they exhibit the same susceptibility to LPS-induced endotoxic shock as wild-type animals and do not show the defects in LPS-induced biosynthesis of inflammatory cytokines known to occur with Mapkapk2-deficient animals (PubMed:14560018). According to another report, both homozygous and heterozygous mutant mice are highly susceptible to skin carcinogenesis induced by DMBA (PubMed:17254968). According to a third report, mutant show embryonic lethality around 11 dpc in a C57BL/6 background (PubMed:15538386).|||Phosphorylated on Thr-182 ERK3/MAPK6 or ERK4/MAPK4; which is the regulatory phosphorylation site and is located on the T-loop/loop 12, leading to activation. Phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11 is subject to debate. Phosphorylated at Ser-115 by PKA/PRKACA, leading to localization to the cytoplasm. Autophosphorylated.|||The role of p38 MAPK kinases is unclear in phosphorylation and activation of Mapkapk5. According to some reports, it interacts and is phosphorylated by p38-alpha/MAPK14 and p38-beta/MAPK11 (PubMed:9480836). According to other reports, it is not activated by p38-alpha/MAPK14 and p38-beta/MAPK11 (PubMed:14560018). An explanation for these discrepancies, might be that the interaction with p38 MAPK kinases is weak and occurs only under specific conditions.|||Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. http://togogenome.org/gene/10090:Surf4 ^@ http://purl.uniprot.org/uniprot/Q545Q2|||http://purl.uniprot.org/uniprot/Q64310 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SURF4 family.|||Embryonic lethality between 3.5 and 9.5 dpc (PubMed:31978056). Conditional deletion in the liver depletes plasma lipids and protects mice from atherosclerosis (PubMed:33186557).|||Endoplasmic reticulum cargo receptor that mediates the export of lipoproteins by recruiting cargos into COPII vesicles to facilitate their secretion. Acts as a cargo receptor for lipoproteins bearing both APOB and APOA1, thereby regulating lipoprotein delivery and the maintenance of lipid homeostasis. Synergizes with the GTPase SAR1B to mediate transport of circulating lipoproteins. Promotes the secretion of PCSK9. Also mediates the efficient secretion of erythropoietin (EPO). May also play a role in the maintenance of the architecture of the endoplasmic reticulum-Golgi intermediate compartment and of the Golgi.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Found in a complex composed at least of SURF4, TMED2 and TMED10 (By similarity). May interact with LMAN1 (By similarity). Interacts with ZFYVE27 and with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701). Interacts with STING1 (By similarity). Interacts with SAR1B (By similarity). Interacts with TMEM41B (By similarity).|||Golgi apparatus membrane|||Membrane|||The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins. http://togogenome.org/gene/10090:Kdf1 ^@ http://purl.uniprot.org/uniprot/A2A9F4 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation ^@ Cell junction|||Cytoplasm|||Expressed in basal and suprabasal layers of the epidermis as well as within the developing hair follicles and the lumen of the esophagus at 18 dpc.|||Plays a role in the regulation of the epidermis formation during early development. Required both as an inhibitor of basal cell proliferation and a promoter of differentiation of basal progenitor cell progeny.|||Shorthand (Shd), a recessive ethylnitrosurea-induced mutant with a frameshift that results in a longer protein with the C-terminal being out of frame. Shd displays shortened and fused limbs and craniofacial malformations, including shortened snout at 12.5 dpc. The affected mice display a thickened epidermis with increased basal keratinocyte proliferation and poorly-differentiated epidermal cells that fail to form a normal barrier at 18.5 dpc. Shd homozygotes died at birth, likely due to the epidermis covering the mouth and nose openings, preventing respiration (PubMed:24075906). http://togogenome.org/gene/10090:Gm20806 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Gsdma2 ^@ http://purl.uniprot.org/uniprot/Q32M21 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A2, N-terminal) that initiates pyroptosis (By similarity). In contrast to Gsdma, not cleaved by bacterial effector protein SpeB (PubMed:35110732).|||Expressed in the gastrointestinal tract, specifically from the middle to the upper region of the gastric mucosa in the glandular stomach.|||Expression is first detected at 16.6-17.5 dpc.|||Homooligomer; homooligomeric ring-shaped pore complex containing 18-36 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.|||Mice lacking Gsdma, Gsdma2 and Gsdma3 are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model.|||Pore-forming protein that causes membrane permeabilization and pyroptosis. Released upon cleavage of Gasdermin-A2, and binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis. Binds to membrane inner leaflet lipids, such as phosphatidylinositol (4,5)-bisphosphate.|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A2, N-terminal).|||This form constitutes the precursor of the pore-forming protein and acts as a sensor of infection: upon bacterial infection, specifically cleaved by some bacterial effector protein, releasing the N-terminal moiety (Gasdermin-A2, N-terminal) that binds to membranes and forms pores, triggering pyroptosis.|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Tmem200b ^@ http://purl.uniprot.org/uniprot/D3Z0P8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM200 family.|||Membrane http://togogenome.org/gene/10090:Shmt1 ^@ http://purl.uniprot.org/uniprot/P50431 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SHMT family.|||Cytoplasm|||Homotetramer (PubMed:11063567). Identified in complex with FAM175B and the other subunits of the BRISC complex, at least composed of FAM175B/ABRO1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1.|||In eukaryotes there are two forms of the enzymes: a cytosolic one and a mitochondrial one.|||Interconversion of serine and glycine. http://togogenome.org/gene/10090:Klc1 ^@ http://purl.uniprot.org/uniprot/E9Q7C9|||http://purl.uniprot.org/uniprot/Q5UE59|||http://purl.uniprot.org/uniprot/Q7M6Z7|||http://purl.uniprot.org/uniprot/Q7M6Z8|||http://purl.uniprot.org/uniprot/Q7M6Z9|||http://purl.uniprot.org/uniprot/Q7M701|||http://purl.uniprot.org/uniprot/Q7M702|||http://purl.uniprot.org/uniprot/Q7TNF4|||http://purl.uniprot.org/uniprot/Q8CD76 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the kinesin light chain family.|||Kinesin is a microtubule-associated force-producing protein that play a role in organelle transport.|||Oligomeric complex composed of two heavy chains and two light chains.|||cytoskeleton http://togogenome.org/gene/10090:Gbx2 ^@ http://purl.uniprot.org/uniprot/P48031 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed during gastrulation in the three primitive germ layers and in the pharyngeal arches. In later stages, expressed in the developing nervous system, midbrain/ hindbrain boundary, cerebellum anlage, certain rhombomeres, regions of the spinal cord, and in the developing dorsal thalamus and corpus striatum.|||Expressed in adult brain, spleen and female genital tract. No expression in heart, liver, lung, kidney, or testis.|||May act as a transcription factor for cell pluripotency and differentiation in the embryo.|||Nucleus http://togogenome.org/gene/10090:Cacna1s ^@ http://purl.uniprot.org/uniprot/Q02789 ^@ Activity Regulation|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily.|||Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.|||Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:28351836). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (PubMed:12871958, PubMed:16550931, PubMed:16638807). Interacts with RYR1 (By similarity). Interacts with STAC, STAC2 and STAC3 (via their SH3 domains) (PubMed:29467163). Interacts with CALM (By similarity).|||Defects in Cacna1s are the cause of muscular dysgenesis (MDG), a lethal autosomal recessive disorder in which there is total lack of excitation-contraction coupling in homozygotes, and which results in complete skeletal muscle paralysis. A single nucleotide deletion yields a protein with an altered and truncated C-terminus.|||Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.|||Phosphorylated. Phosphorylation by PKA activates the calcium channel. Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation at Ser-1575 is involved in beta-adrenergic-mediated regulation of the channel.|||Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.|||T-tubule|||The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690.|||The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction. http://togogenome.org/gene/10090:Dsn1 ^@ http://purl.uniprot.org/uniprot/Q9CYC5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Also interacts with KNL1, CBX3 and CBX5. Interacts with KNSTRN.|||Nucleus|||Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis.|||kinetochore http://togogenome.org/gene/10090:Basp1 ^@ http://purl.uniprot.org/uniprot/Q91XV3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BASP1 family.|||Cell membrane|||growth cone http://togogenome.org/gene/10090:Retreg2 ^@ http://purl.uniprot.org/uniprot/Q6NS82 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RETREG family.|||Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Required for collagen quality control in a LIR motif-independent manner (PubMed:34338405).|||Endoplasmic reticulum membrane|||Interacts with ATG8 family modifier proteins MAP1LC3A, MAP1LC3B, GABARAPL1 and GABARAPL2 (PubMed:34338405). Also interacts with ATG8 family modifier protein GABARAP (By similarity). Interacts with CANX (By similarity).|||The LIR motif interacts with ATG8 family proteins.|||Widely expressed with highest levels in brain, lung, heart, liver and kidney (at protein level) (PubMed:34338405). Mainly expressed in the central nervous system and in parenchymatous organs including liver, lung and kidney. http://togogenome.org/gene/10090:Pih1d2 ^@ http://purl.uniprot.org/uniprot/Q8CHR9 ^@ Similarity ^@ Belongs to the PIH1 family. http://togogenome.org/gene/10090:Atp2c1 ^@ http://purl.uniprot.org/uniprot/Q3UZR5|||http://purl.uniprot.org/uniprot/Q69ZL4|||http://purl.uniprot.org/uniprot/Q80XR2|||http://purl.uniprot.org/uniprot/Q8BMS7 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway (By similarity). Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (By similarity). Plays a primary role in the maintenance of Ca(2+) homeostasis in the trans-Golgi compartment with a functional impact on Golgi and post-Golgi protein sorting as well as a structural impact on cisternae morphology. Responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity (By similarity). Participates in Ca(2+) and Mn(2+) ions uptake into the Golgi store of hippocampal neurons and regulates protein trafficking required for neural polarity (PubMed:19793975). May also play a role in the maintenance of Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity (By similarity).|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.|||Catalyzes the hydrolysis of ATP coupled with the transport of calcium.|||Expressed in hippocampal neurons in the CA3 region of the Amon's horn (at protein level) (PubMed:19793975). Expressed in brain, heart, lung, stomach, liver, colon and mammary gland (PubMed:17597066).|||Golgi stack membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Monomer. Homodimer.|||Mutant mice, born at the expected Mendelian rate, show growth retardation and exencephaly by 9.5 dpc and die by 10.5 dpc.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Tmem150c ^@ http://purl.uniprot.org/uniprot/Q8C8S3 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DRAM/TMEM150 family.|||Cell membrane|||Component of a mechanosensitive cation channel. Confers mechanically activated (MA) currents with slow inactivation kinetics. May contribute to proprioception (PubMed:27321926).|||Deficient mice exhibit loss of coordinated movements and abnormal gait.|||High expression in the epididymis, pancreas, dorsal-root ganglion, eye, brain, and spinal cord. Expressed in muscle spindle afferents (at protein level)(PubMed:27321926).|||Lysosome membrane|||Tentonin comes from the Greek 'tentono' meaning to stretch.|||The function of the TMEM150C complex is debated. One study confirms that naive cells expressing TMEM150C is activated by mechanically stimuli but this response is absent in CRISPR-Cas9 PIEZO1 knockout cell lines suggesting that TMEM150C is not sufficient to function as mechanically activated channels but is a modulatory protein of PIEZO1 (PubMed:28426961). In another study, based on coexpression of TMEM150C and PEIZO1 and mutant variants of TMEM150C supports that TMEM150C is a pore-forming unit, and not an amplifying adapter for PIEZO1 activity (PubMed:28426962). http://togogenome.org/gene/10090:Nsd2 ^@ http://purl.uniprot.org/uniprot/Q8BVE8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.|||Chromosome|||Depending on the experimental set up and substrate used, NSD2 has been shown to mono-, di- or tri-methylate 'Lys-27', 'Lys-36' or 'Lys-79' of histone H3 and 'Lys-20' or 'Lys-44' of histone H4 (By similarity). However, dimethylation of nucleosomal histone H3 at 'Lys-36' (H3K36me2) is likely to be the physiological reaction catalyzed by NSD2 (By similarity).|||During B-cell development, expressed in early B2 cell progenitors (pre- and pro-B cells) with a decrease in expression at later stages.|||Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (By similarity). Mono-, di- and tri-methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2, H3K27me3) (PubMed:18172012). Methylation of histone H3 at 'Lys-27' is controversial (By similarity). May act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment (PubMed:18172012).|||Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:19483677, PubMed:32862441, PubMed:31636135). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:19483677). Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (By similarity). However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells (PubMed:19483677). By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes (PubMed:19483677, PubMed:31636135, PubMed:32862441, PubMed:23241889). In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation (PubMed:19483677). During heart development, associates with transcription factor NKX2-5 to repress transcription of NKX2-5 target genes (PubMed:19483677). Plays an essential role in adipogenesis, by regulating expression of genes involved in pre-adipocyte differentiation (By similarity). During T-cell receptor (TCR) and CD28-mediated T-cell activation, promotes the transcription of transcription factor BCL6 which is required for follicular helper T (Tfh) cell differentiation (PubMed:31636135). During B-cell development, required for the generation of the B1 lineage (PubMed:32862441). During B2 cell activation, may contribute to the control of isotype class switch recombination (CRS), splenic germinal center formation, and the humoral immune response (PubMed:32862441). Plays a role in class switch recombination of the immunoglobulin heavy chain (IgH) locus during B-cell activation (PubMed:23241889). By regulating the methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 recruitment to the IgH switch region and promotes the transcription of IgA (PubMed:23241889).|||Incorrectly indicated as originating from human.|||Induced in CD4(+) T-cell in response to T-cell receptor (TCR) and CD28 stimulation (at protein level) (PubMed:31636135). Induced in B2-cells by IgM antibodies or lipopolysaccharide (LPS) stimulation (PubMed:32862441).|||Interacts with HDAC1 (PubMed:19483677). Interacts (via PHD-type zinc fingers 1, 2 and 3) with SALL1 (PubMed:19483677). Interacts (via PHD-type 1, 2 and 3) with SALL4 (PubMed:19483677). Interacts with NANOG (PubMed:19483677). Interacts with OGT (PubMed:19483677). Interacts (via HMG box) with NKX2-5 (PubMed:19483677).|||Nucleus|||Offspring number is low at birth (PubMed:19483677). After birth, pups have growth retardation and die within 10 days (PubMed:19483677). At 15.5 dpc, levels of trimethylated 'Lys-36' on histone H3 are reduced (PubMed:19483677). At 18.5 dpc, embryos are smaller with midline fusion defects due to a lack of ossification centers and some have cleft palates (PubMed:19483677). They also have heart defects including atrial and ventricular septal defects (PubMed:19483677). Conditional knockout in CD4(+) T-cells, reduces dimethylation of histone H3 at 'Lys-36' at the Bcl6 gene locus in response to T-cell activation which results in impaired Bcl6 expresseion (PubMed:31636135). Following immunization with ovalbumin antigen or sheep red blood cells, or infection with LCMV virus, follicular helper T (Tfh) cell differentiation and germinal center B cell response are reduced (PubMed:31636135). Also, following infection with LCMV virus, clearance of the virus is delayed (PubMed:31636135). No defect in T-cell development (PubMed:31636135).|||Ubiquitously expressed in early development (PubMed:9618163). Highly expressed in neuroepithelium at 10.5 dpc, and in the forebrain, midbrain, frontal facial region, jaw, heart but not in the endocardial cushion, and cartilage primordial at 14.5 dpc (PubMed:19483677). http://togogenome.org/gene/10090:Uqcrh ^@ http://purl.uniprot.org/uniprot/P99028 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UQCRH/QCR6 family.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783).|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nebl ^@ http://purl.uniprot.org/uniprot/Q9DC07 ^@ Function|||Subcellular Location Annotation ^@ Binds to actin and plays an important role in the assembly of the Z-disk. Isoform 2 might play a role in the assembly of focal adhesion (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Mcee ^@ http://purl.uniprot.org/uniprot/Q9D1I5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methylmalonyl-CoA epimerase family.|||Methylmalonyl-CoA epimerase involved in propionyl-CoA metabolism.|||Mitochondrion http://togogenome.org/gene/10090:Grm4 ^@ http://purl.uniprot.org/uniprot/A0A140T8R6|||http://purl.uniprot.org/uniprot/G3XA00|||http://purl.uniprot.org/uniprot/Q68EF4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity (By similarity).|||Interacts with PICK1.|||Membrane http://togogenome.org/gene/10090:Them5 ^@ http://purl.uniprot.org/uniprot/Q9CQJ0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the THEM4/THEM5 thioesterase family.|||Has acyl-CoA thioesterase activity towards long-chain (C16 and C18) fatty acyl-CoA substrates, with a preference for linoleoyl-CoA and other unsaturated long-chain fatty acid-CoA esters (By similarity). Plays an important role in mitochondrial fatty acid metabolism, and in remodeling of the mitochondrial lipid cardiolipin (PubMed:22586271). Required for normal mitochondrial function (PubMed:22586271).|||Homodimer.|||Mitochondrion matrix|||With increasing age, mice develop fatty liver, due to impaired mitochondrial fatty acid metabolism, and impaired remodeling of the mitochondrial lipid cardiolipin. Mitochondria contain increased levels of monolysocardiolipin, and decreased levels of linoleic and linolenic acid. The altered fatty acid metabolism leads to decreased mitochondrial beta-oxidation and ketone body formation. Mitochondria show abnormal, elongated morphology, and their function is impaired. http://togogenome.org/gene/10090:Erg28 ^@ http://purl.uniprot.org/uniprot/Q9ERY9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ERG28 family.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Ccnl2 ^@ http://purl.uniprot.org/uniprot/Q9JJA7 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family. Cyclin L subfamily.|||Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions (By similarity).|||Interacts with CDK11A, CDK11B, CDK12, CDK13 and POLR2A, the hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II. May form a ternary complex with CDK11B and casein kinase II (CKII). Interacts with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 and SRSF7/SLU7.|||Involved in pre-mRNA splicing. May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus speckle|||Widely expressed (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Nudt21 ^@ http://purl.uniprot.org/uniprot/Q9CQF3 ^@ Caution|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated mainly by p300/CBP, recruited to the complex by CPSF6. Acetylation decreases interaction with PAPAO. Deacetylated by the class I/II HDACs, HDAC1, HDAC3 and HDAC10, and by the class III HDACs, SIRT1 and SIRT2.|||Belongs to the Nudix hydrolase family. CPSF5 subfamily.|||Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. NUDT21/CPSF5 activates indirectly the mRNA 3'-processing machinery by recruiting CPSF6 and/or CPSF7. Binds to 5'-UGUA-3' elements localized upstream of pA signals that act as enhancers of pre-mRNA 3'-end processing. The homodimer mediates simultaneous sequence-specific recognition of two 5'-UGUA-3' elements within the pre-mRNA (By similarity). Plays a role in somatic cell fate transitions and pluripotency by regulating widespread changes in gene expression through an APA-dependent function(PubMed:29249356). Binds to chromatin (PubMed:18032416). Binds to, but does not hydrolyze mono- and di-adenosine nucleotides (By similarity).|||Cytoplasm|||Expressed in testis (PubMed:18032416). Expressed in male germ cells (at protein level) (PubMed:18032416).|||Homodimer (via N- and C-terminus); binds RNA as homodimer. Component of the cleavage factor Im (CFIm) complex which is a heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7. The cleavage factor Im (CFIm) complex associates with the CPSF and CSTF complexes to promote the assembly of the core mRNA 3'-processing machinery. Interacts with CPSF6 (via the RRM domain); this interaction is direct and enhances binding to RNA. Interacts with CPSF7. Interacts with FIP1L1; this interaction occurs in a RNA sequence-specific manner. Interacts with PABPN1 (By similarity). Interacts (via N-terminus) with PAPOLA (via C-terminus); this interaction is direct and diminished by acetylation (PubMed:11716503). Interacts with SNRNP70 (By similarity). Interacts with VIRMA (By similarity).|||Lacks the conserved metal-binding residues in the NUDIX motif and is not expected to have hydrolase activity.|||Nucleus|||Up-regulated during spermatogenesis (PubMed:18032416). http://togogenome.org/gene/10090:Albfm1 ^@ http://purl.uniprot.org/uniprot/F8VQ07 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Ccl11 ^@ http://purl.uniprot.org/uniprot/P48298 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||By interferon gamma and lipopolysaccharides (LPS) (PubMed:7568052). By interleukin-13 (IL13) (PubMed:15647285).|||Expressed constitutively in the thymus. Expression inducible in the lung (type I alveolar epithelial cells), intestine, heart, spleen, kidney.|||In response to the presence of allergens, this protein directly promotes the accumulation of eosinophils (a prominent feature of allergic inflammatory reactions), but not lymphocytes, macrophages or neutrophils (PubMed:7568052, PubMed:8574847). Binds to CCR3 (By similarity).|||Secreted http://togogenome.org/gene/10090:Man1b1 ^@ http://purl.uniprot.org/uniprot/A2AJ15 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 47 family.|||Endoplasmic reticulum membrane|||Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2) (By similarity). http://togogenome.org/gene/10090:Rilp ^@ http://purl.uniprot.org/uniprot/Q5ND29 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Interacts with RAB7A. Interacts with RAB34 (By similarity). Identified in a complex with MREG and DCTN1; interacts directly with MREG (PubMed:22275436). Interacts with CLN3 (By similarity). Interacts with FLCN; the interaction is direct and promotes association between RILP and RAB34 (By similarity).|||Late endosome membrane|||Lysosome membrane|||Rab effector playing a role in late endocytic transport to degradative compartments. Involved in the regulation of lysosomal morphology and distribution. Induces recruitment of dynein-dynactin motor complexes to Rab7A-containing late endosome and lysosome compartments. Promotes centripetal migration of phagosomes and the fusion of phagosomes with the late endosomes and lysosomes.|||phagosome membrane http://togogenome.org/gene/10090:Itgb4 ^@ http://purl.uniprot.org/uniprot/A2A863|||http://purl.uniprot.org/uniprot/A2A864 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin beta chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. Beta-4 associates with alpha-6. Interacts (via cytoplasmic region) with COL17A1 (via cytoplasmic region). Interacts (via cytoplasmic region) with DST isoform 3 (via N-terminus). Interacts (via cytoplasmic domain) with DST (via N-terminus). Interacts with RAC1. ITGA6:ITGB4 is found in a ternary complex with NRG1 and ERBB3. ITGA6:ITGB4 is found in a ternary complex with IGF1 and IGF1R. ITGA6:ITGB4 interacts with IGF2.|||Integrin alpha-6/beta-4 is a receptor for laminin. It plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling. ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling.|||Membrane|||Palmitoylated by DHHC3 at several cysteines of the membrane-proximal region, enhancing stability and cell surface expression. Palmitoylation also promotes secondary association with tertaspanins (By similarity).|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site.|||The fibronectin type-III-like domains bind BPAG1 and plectin and probably also recruit BP230.|||hemidesmosome http://togogenome.org/gene/10090:Actrt1 ^@ http://purl.uniprot.org/uniprot/Q9D9J3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the actin family.|||Cytoplasm|||Negatively regulates the Hedgehog (SHH) signaling. Binds to the promoter of the SHH signaling mediator, GLI1, and inhibits its expression.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Zfp809 ^@ http://purl.uniprot.org/uniprot/G3X9G7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Transcription factor specifically required to repress retrotransposons in embryonic stem cells. Recognizes and binds retroviral DNA sequences from a large subset of mammalian retroviruses and retroelements and repress their expression by recruiting a repressive complex containing TRIM28/KAP1 (PubMed:19270682). http://togogenome.org/gene/10090:Mrs2 ^@ http://purl.uniprot.org/uniprot/Q5NCE8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.|||Magnesium transporter that mediates the influx of magnesium into the mitochondrial matrix. Required for normal expression of the mitochondrial respiratory complex I subunits.|||Mitochondrion inner membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Il17c ^@ http://purl.uniprot.org/uniprot/Q8K4C5 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-17 family.|||Binds to a heterodimer formed by IL17RA and IL17RE.|||Cytokine that plays a crucial role in innate immunity of the epithelium, including to intestinal bacterial pathogens, in an autocrine manner. Stimulates the production of antibacterial peptides and pro-inflammatory molecules for host defense by signaling through the NFKB and MAPK pathways. Acts synergically with IL22, TNF and IL1B in inducing antibacterial peptides. May have protective function by maintaining epithelial homeostasis after an inflammatory challenge, such as that caused in the intestine by dextran sulfate sodium in a colitis model. May also promote an inflammatory phenotype, such as skin in a psoriasis model. Enhanced IL17C/IL17RE signaling may also lead to greater susceptibility to autoimmune diseases, such as autoimmune encephalitis.|||Expressed by epithelial cells after bacterial challenge. Low expression, if any, in lymphocytes.|||Mutant animals develop normally and do not exhibit any pronounced immunological deficiency.|||Secreted|||Up-regulated in the colon, but not in spleen or liver, during infection with Citrobacter rodentium. Up-regulated by various inflammatory cytokines, including TNF, IL1B, IL17A and IL17F in colon epithelial cells. http://togogenome.org/gene/10090:Calhm1 ^@ http://purl.uniprot.org/uniprot/A0A1Y1C8H8|||http://purl.uniprot.org/uniprot/D3Z291 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the CALHM family.|||Cell membrane|||Endoplasmic reticulum membrane|||Homohexamer (By similarity). Associates with CALHM3 as a pore-forming subunit in an hetero-hexameric channel complex (PubMed:29681531).|||Impaired perceptions of sweet, bitter and umami compounds. Mice are viable and fertile, with no visible morphological abnormalities in their taste buds or any altered expression of taste-related marker genes. They do however display a loss of both preference for sweet and umami compounds and for avoidance of bitter compounds. Perceptions of sour and salty tastes are unaffected. Reduced voltage-gated currents in type II cells and taste-evoked ATP release from taste buds without affecting the excitability of taste cells by taste stimuli. Elderly males and females do not show defects in spatial learning and memory retrieving.|||Inhibited by Gd(3+), Ruthenium Red, and Zn(2+) and partially inhibited by 2-aminoethoxydiphenyl borate.|||Membrane|||Pore-forming subunit of a voltage-gated ion channel, also permeable to larger molecules including ATP, required for sensory perception of sweet, bitter and umami tastes (PubMed:23467090). Specifically present in type II taste bud cells, where it plays a central role in sweet, bitter and umami taste perception by inducing ATP release from the cell, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (PubMed:23467090). Together with CALHM3, forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells (TBCs) (PubMed:29681531). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration (PubMed:22711817). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of Ca(2+), Na(+) and K(+), as well as permeation of monovalent anions (PubMed:22711817). Acts as an activator of the ERK1 and ERK2 cascade (By similarity). Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (By similarity). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent manner (By similarity).|||Specifically expressed in type II taste bud cells. Not expressed in brain. http://togogenome.org/gene/10090:Snx7 ^@ http://purl.uniprot.org/uniprot/F8WI30|||http://purl.uniprot.org/uniprot/Q5M8N3 ^@ Similarity ^@ Belongs to the sorting nexin family. http://togogenome.org/gene/10090:Ccl1 ^@ http://purl.uniprot.org/uniprot/P10146|||http://purl.uniprot.org/uniprot/Q0VB35 ^@ Function|||Induction|||Polymorphism|||Similarity|||Subcellular Location Annotation ^@ Belongs to the intercrine beta (chemokine CC) family.|||Cytokine that is chemotactic for neutrophils.|||Produced by T-cell after stimulation by antigen or induction by concanavalin a (Con-A).|||Secreted|||The polymorphisms in strains DBA/2J and SJL/J may be associated with severity of clinical symptoms of experimental allergic encephalomyelitis, an animal model of multiple sclerosis, and susceptibility to the monophasic remitting/nonrelapsing form of the disease. http://togogenome.org/gene/10090:Pank2 ^@ http://purl.uniprot.org/uniprot/Q7M753 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II pantothenate kinase family.|||Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.|||Homodimer.|||Inhibited by acetyl-CoA (PubMed:17825826). Inhibited by calcium hopantenate (PubMed:17379144). Activated by palmitoylcarnitine (PubMed:17825826).|||Single knockout mice show a reduction in pantothenate kinase (PANK) activity of about 30% and 60% in the liver and brain respectively. Pank1 and Pank2 double knockout mice develop progressively severe hypoglycemia and hyperketonemia by postnatal day 10 leading to their death by day 17. A reduction in PANK activity of about 90-95% seen in the liver and brain and hepatocytes show reduced NADH levels.|||cytosol http://togogenome.org/gene/10090:Uqcr10 ^@ http://purl.uniprot.org/uniprot/Q5NCJ9|||http://purl.uniprot.org/uniprot/Q8R1I1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UQCR10/QCR9 family.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783). Interacts with STMP1 (PubMed:35101990).|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein, 2 core protein subunits, and additional low-molecular weight protein subunits.|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lyz2 ^@ http://purl.uniprot.org/uniprot/A0A077S2U6|||http://purl.uniprot.org/uniprot/P08905 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 22 family.|||Expressed weakly in myeloblasts, moderately in immature macrophages, and strongly in both mature macrophages and macrophage-rich tissues.|||Lysozyme C is capable of both hydrolysis and transglycosylation; it shows also a slight esterase activity. It acts rapidly on both peptide-substituted and unsubstituted peptidoglycan, and slowly on chitin oligosaccharides.|||Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Lyz2 is active against a range of Gram-positive and Gram-negative bacteria. More effective than Lyz1 in killing Gram-negative bacteria. Lyz1 and Lyz2 are equally effective in killing Gram-positive bacteria.|||Mice display increased inflammation in response to M.luteus infection, impaired digestion of M.luteus cell walls, decreased clearance of P.aeruginosa from infected airways, increased susceptibility to K.pneumoniae infection and increased bacterial burden and mortality following infection with various Gram-negative bacteria. Lyz2 is non-immunogenic in wild-type mice but is rendered immunogenic in mutants.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Txndc5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Y7|||http://purl.uniprot.org/uniprot/E9PXX7|||http://purl.uniprot.org/uniprot/Q3TEE8|||http://purl.uniprot.org/uniprot/Q3UWX1|||http://purl.uniprot.org/uniprot/Q91W90 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum lumen|||Expressed at high levels in plasma cells and at very low levels in all other cells and tissues examined (at protein level).|||Protein disulfide isomerase of the endoplasmic reticulum lumen involved in the formation of disulfide bonds in proteins (PubMed:12930873, PubMed:14971039). Can reduce insulin disulfide bonds (PubMed:14971039). http://togogenome.org/gene/10090:Focad ^@ http://purl.uniprot.org/uniprot/A2AKG8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed by glial and neuronal cells in brain.|||Interacts with VCL.|||Required for the maintenance of SKIC2 and SKIC3 proteostatic levels in the liver. May be involved in the regulation of RNA degradation by the exosome complex (By similarity). Potential tumor suppressor in gliomas.|||cytosol|||focal adhesion http://togogenome.org/gene/10090:Il21r ^@ http://purl.uniprot.org/uniprot/Q9JHX3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||C-mannosylated at Trp-214 in the WSXWS motif, the sugar chain makes extensive hydrogen bonds with Asn-73 sugar, and bridges the two fibronectin domains transforming the V-shaped receptor into an A-frame.|||Heterodimer with the common gamma subunit. Associates with JAK1.|||Membrane|||Selectively expressed in lymphoid tissues. Most highly expressed in thymus and spleen.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||This is a receptor for interleukin-21. http://togogenome.org/gene/10090:Ms4a6d ^@ http://purl.uniprot.org/uniprot/Q2TVW7|||http://purl.uniprot.org/uniprot/Q99N07 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed in thymus, spleen, intestine, colon, testis, heart, liver, brain, kidney, peripheral lymph node and bone marrow.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Pla2g2e ^@ http://purl.uniprot.org/uniprot/Q3UG05|||http://purl.uniprot.org/uniprot/Q9QUL3 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 2 Ca(2+) ions per subunit.|||Cytoplasm|||Expressed abundantly in hair follicles during the anagen phase. Low expression is observed before birth, then follows hair cycle progression: up-regulated markedly during P5-P15 (anagen phase), declining to nearly the basal level during P20-P25 (catagen and telogen) and then increasing again at P30 (next anagen).|||Highly expressed in skin and uterus, and at lower levels in various other tissues (PubMed:27226633, PubMed:10531313, PubMed:10681567, PubMed:11922621). Expressed in hair follicles, specifically localized in companion cells of the outer root sheath and cuticular cells of the inner root sheath in hair follicles during anagen (PubMed:27226633). Expressed in white and brown adipose tissue (PubMed:24910243).|||Mutant mice show abnormal hair follicle ultrastructure characterized by defects in the companion layer, the inner root sheath (IRS) and hair shaft. Mutant IRS cells have large cytoplasmic cysts and pyknotic nuclei and are devoid of keratohyalin granules, whereas the cuticle is abnormally dissociated from the hair cortex and medulla, indicative of impaired hair follicle development (PubMed:27226633). Mutant mice are protected from obesity and hyperlipidemia in response to high-fat diet (PubMed:24910243).|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids (PubMed:11922621, PubMed:10531313). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), releasing various unsaturated fatty acids including oleoate, linoleoate, arachidonate, docosahexaenoate and lysophosphatidylethanolamines in preference to lysophosphatidylcholines (By similarity). In response to high-fat diet, hydrolyzes minor lipoprotein phospholipids including phosphatidylserines, phosphatidylinositols and phosphatidylglycerols, altering lipoprotein composition and fat storage in adipose tissue and liver (PubMed:24910243). May act in an autocrine and paracrine manner (By similarity). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria (By similarity). Acts as a hair follicle phospholipase A2. Selectively releases lysophosphatidylethanolamines (LPE) and various unsaturated fatty acids in skin to regulate hair follicle homeostasis (PubMed:27226633). May regulate the inflammatory response by releasing arachidonate, a precursor of prostaglandins and leukotrienes. Upon allergen exposure, may participate in allergic inflammatory response by enhancing leukotriene C4 synthesis and degranulation in mast cells (PubMed:11922621).|||Up-regulated in thymus, small intestine, brain, heart, testis, kidney and lung upon endotoxin challenge (PubMed:10681567, PubMed:11922621). Detected in alveolar macrophage-like cells upon endotoxin challenge (PubMed:10681567). Up-regulated in white and brown adipocytes upon high-fat diet (PubMed:24910243). Up-regulated in ear epidermis in response to topical dermatitis agent 2,4-dinitrobenzene (DNFB) (PubMed:11922621). http://togogenome.org/gene/10090:Defb36 ^@ http://purl.uniprot.org/uniprot/Q8K3U4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Acy1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J050|||http://purl.uniprot.org/uniprot/Q99JW2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M20A family.|||Binds 2 Zn(2+) ions per subunit.|||Catalyzes the hydrolysis of N-acetylated amino acids to acetate and free amino acids.|||Cytoplasm|||Homodimer (By similarity). Interacts with SPHK1. http://togogenome.org/gene/10090:Tmem60 ^@ http://purl.uniprot.org/uniprot/Q8K174 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Vmn1r5 ^@ http://purl.uniprot.org/uniprot/B2RQT2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc16a13 ^@ http://purl.uniprot.org/uniprot/Q8CE94 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Golgi apparatus membrane|||Proton-linked monocarboxylate transporter. May catalyze the transport of monocarboxylates across the plasma membrane. http://togogenome.org/gene/10090:Sspn ^@ http://purl.uniprot.org/uniprot/Q62147 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. Preferentially associates with the sarcoglycan subcomplex of the DGC (By similarity).|||Postsynaptic cell membrane|||sarcolemma http://togogenome.org/gene/10090:Ppil2 ^@ http://purl.uniprot.org/uniprot/Q9D787 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclophilin-type PPIase family. PPIL2 subfamily.|||Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with PRPF8/PRP8, EFTUD2/SNU114 and PLRG1 (By similarity). Interacts with isoform 2 of BSG (By similarity). Interacts (via the PPIase cyclophilin-type domain) with CRNKL1; they may form a trimeric complex with HSP90.|||Despite the fact that it belongs to the cyclophilin-type PPIase family, it has probably no peptidyl-prolyl cis-trans isomerase activity due to the presence of a tyrosine instead of a tryptophan at position 389.|||Has a ubiquitin-protein ligase activity acting as an E3 ubiquitin protein ligase or as an ubiquitin-ubiquitin ligase promoting elongation of ubiquitin chains on substrates. By mediating 'Lys-48'-linked polyubiquitination of proteins could target them for proteasomal degradation. May also function as a chaperone, playing a role in transport to the cell membrane of BSG/Basigin for instance. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus http://togogenome.org/gene/10090:Sfxn4 ^@ http://purl.uniprot.org/uniprot/Q925N1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sideroflexin family.|||Largely restricted to kidney, brain and heart.|||Mitochondrial amino-acid transporter (By similarity). Does not act as a serine transporter: not able to mediate transport of serine into mitochondria (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Wfdc18 ^@ http://purl.uniprot.org/uniprot/P62810 ^@ Function|||Subcellular Location Annotation ^@ Could have proteinase inhibiting capacity.|||Secreted http://togogenome.org/gene/10090:Rgs3 ^@ http://purl.uniprot.org/uniprot/Q9DC04 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds the GNB1-GNG2 heterodimer (By similarity). Binds EFNB1 and EFNB2.|||Cell membrane|||Cytoplasm|||Detected in embryos from E8.5-16.5 in cortical ventricular zone, dorsal root ganglia and cerebellar primordia. Isoform 3 is detected in testis and in spermatocytes from newborn mice. Levels increase and reach a maximum after 21 days; after this they decrease again. Long isoforms are widely expressed.|||Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form. Down-regulates G-protein-mediated release of inositol phosphates and activation of MAP kinases.|||ISGylated.|||Nuclear.|||Nucleus|||Phosphorylated by cyclic GMP-dependent protein kinase. http://togogenome.org/gene/10090:Pdyn ^@ http://purl.uniprot.org/uniprot/O35852|||http://purl.uniprot.org/uniprot/Q3UZW2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the opioid neuropeptide precursor family.|||Dynorphin peptides differentially regulate the kappa opioid receptor. Dynorphin A(1-13) has a typical opioid activity, it is 700 times more potent than Leu-enkephalin.|||Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.|||Leumorphin has a typical opioid activity and may have anti-apoptotic effect.|||Secreted http://togogenome.org/gene/10090:Rragd ^@ http://purl.uniprot.org/uniprot/B1AWT2|||http://purl.uniprot.org/uniprot/Q7TT45 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GTR/RAG GTP-binding protein family.|||Cytoplasm|||Expressed in the distal tubule of the kidney.|||Forms a heterodimer with RRAGA in a sequence-independent manner and RRAGB. Heterodimerization stabilizes RRAG proteins. The GDP-bound form of RRAGD (in complex with the GTP-bound form of RRAGA or RRAGB), interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (By similarity). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with NOL8. Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGD and is negatively regulated by amino acids (By similarity). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor. Interacts with SESN1, SESN2 and SESN3 (PubMed:25259925). The GDP-bound form interacts with TFEB (By similarity). The GDP-bound form interacts with TFE3 (PubMed:30595499).|||Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.|||Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the MTOR signaling cascade by amino acids. Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3.|||Lysosome|||Lysosome membrane|||Nucleus|||The activation of RagD/RRAGD is mediated by a GTPase activating protein (GAP). In high-amino acid conditions, activated by GTPase activating protein FLCN that stimulates RRAGD GTPase activity to turn it into its active GDP-bound form (By similarity). In response to amino acid depletion, the GATOR1 complex inactivates RagC/RRAGC by securing the GTP-bound inactive form (By similarity). http://togogenome.org/gene/10090:Cog8 ^@ http://purl.uniprot.org/uniprot/Q9JJA2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG8 family.|||Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.|||Golgi apparatus membrane|||Required for normal Golgi function. http://togogenome.org/gene/10090:Nccrp1 ^@ http://purl.uniprot.org/uniprot/G3X9C2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Promotes cell proliferation.|||Strongly expressed in kidney. Weakly expressed in stomach, colon, duodenum and prostate. http://togogenome.org/gene/10090:Strc ^@ http://purl.uniprot.org/uniprot/Q8VIM6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the stereocilin family.|||Cell surface|||Essential to the formation of horizontal top connectors between outer hair cell stereocilia.|||Strongly expressed in the inner ear, detected in the testis, and barely detected in the eye. Detected in the six sensory areas of the inner ear by immunofluorescence. Expressed only in the sensory hair cells and associated with the stereocilia, the stiff microvilli forming the structure for mechanoreception of sound stimulation.|||kinocilium|||stereocilium http://togogenome.org/gene/10090:Or4p19 ^@ http://purl.uniprot.org/uniprot/Q0VB29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zpbp2 ^@ http://purl.uniprot.org/uniprot/Q5FWC7|||http://purl.uniprot.org/uniprot/Q6X786 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the zona pellucida-binding protein Sp38 family.|||Expressed from the mid-pachytene spermatocyte stage to the early elongating spermatid stage.|||Expressed specifically in male germ cells.|||Is implicated in sperm-oocyte interaction during fertilization.|||Male mice are subfertile with sperm showing reduced ability to penetrate zona pellucida and displaying subtle morphological deformation, including shortened apical hook, smaller apical angle and bulges in acrosome region.|||N-glycosylated.|||Secreted|||acrosome http://togogenome.org/gene/10090:Ddx54 ^@ http://purl.uniprot.org/uniprot/Q8K4L0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX54/DBP10 subfamily.|||Has RNA-dependent ATPase activity. Represses the transcriptional activity of nuclear receptors (By similarity).|||Interacts in a hormone-dependent manner with nuclear receptors.|||nucleolus http://togogenome.org/gene/10090:Sypl2 ^@ http://purl.uniprot.org/uniprot/O89104 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the synaptophysin/synaptobrevin family.|||Expressed abundantly in skeletal muscle and at lower levels in the kidney.|||Involved in communication between the T-tubular and junctional sarcoplasmic reticulum (SR) membranes.|||Membrane http://togogenome.org/gene/10090:Shc3 ^@ http://purl.uniprot.org/uniprot/Q61120 ^@ Function|||PTM|||Subunit|||Tissue Specificity ^@ Interacts with the Trk receptors in a phosphotyrosine-dependent manner. Once activated, binds to GRB2. Interacts with activated EGF receptors (By similarity).|||Predominantly expressed in the adult brain.|||Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons (By similarity).|||Tyrosine phosphorylated. http://togogenome.org/gene/10090:Rfx6 ^@ http://purl.uniprot.org/uniprot/Q8C7R7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RFX family.|||By Neurog3.|||Expressed initially broadly in the definitive endoderm after gastrulation, becomes restricted to the gut and pancreatic bud at mid gestation, and is reactivated by Neurog3 in islet progenitor cells and is ultimately restricted to pancreatic islets in the mature pancreas (at protein level).|||In the adult pancreas, expression is restricted to the islets where it could be detected in all endocrine lineages.|||Interacts with RFX3 (PubMed:20148032).|||Mice were born at the expected Mendelian ratio, but fail to feed normally, exhibit gross bowel distension due to small bowel obstruction and die within 2 days post partum. Some, but not all, of the animals also have reduced pancreas size. pancreata had almost no expression of the islet hormones genes, except for PP (polypeptide-producing).|||Nucleus|||Transcription factor required to direct islet cell differentiation during endocrine pancreas development. Specifically required for the differentiation of 4 of the 5 islet cell types and for the production of insulin. Not required for pancreatic PP (polypeptide-producing) cells differentiation. Acts downstream of NEUROG3 and regulates the transcription factors involved in beta-cell maturation and function, thereby restricting the expression of the beta-cell differentiation and specification genes, and thus the beta-cell fate choice. Activates transcription by forming a heterodimer with RFX3 and binding to the X-box in the promoter of target genes (PubMed:20148032). Involved in glucose-stimulated insulin secretion by promoting insulin and L-type calcium channel gene transcription (By similarity). http://togogenome.org/gene/10090:Ppp6r3 ^@ http://purl.uniprot.org/uniprot/G5E8R4|||http://purl.uniprot.org/uniprot/Q922D4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAPS family.|||Cytoplasm|||Nucleus|||Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP6C and ANKRD28 (By similarity).|||Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. May have an important role in maintaining immune self-tolerance (By similarity).|||Strongest expression observed in lung, spleen, bladder and liver and weaker levels present in brain, heart, kidney, skeletal muscle and pancreas. http://togogenome.org/gene/10090:Inpp4b ^@ http://purl.uniprot.org/uniprot/E9PVM1|||http://purl.uniprot.org/uniprot/E9PVM3|||http://purl.uniprot.org/uniprot/Q1A6U9|||http://purl.uniprot.org/uniprot/Q1A6V1|||http://purl.uniprot.org/uniprot/Q3URI3|||http://purl.uniprot.org/uniprot/Q6P1Y8 ^@ Activity Regulation|||Function|||Similarity ^@ Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.|||Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-bisphosphate (By similarity). Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles (By similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (By similarity).|||Strongly inhibited by inositol hexakisphosphate. http://togogenome.org/gene/10090:Kremen2 ^@ http://purl.uniprot.org/uniprot/Q8K1S7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Animals with a double knockout of KREM1 and KREM2 exhibit enhanced Wnt signaling accompanied by ectopic postaxial forelimb digits and expanded apical ectodermal ridges. They also exhibit increased bone volume and bone formation rates. Triple knockout mice KREM1/KREM2/DKK1 exhibit enhanced growth of ectopic digits.|||Binding to ERLEC1 is mediated by the oligosaccharides linked to the kringle domain.|||Expressed in the developing brain and developing limb buds.|||Interacts with ERLEC1 (PubMed:16531414). Forms a ternary complex with DKK1 and LRP6 (PubMed:12050670).|||Membrane|||Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6 (PubMed:12050670). Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation (PubMed:18505822). http://togogenome.org/gene/10090:Tob1 ^@ http://purl.uniprot.org/uniprot/Q61471 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex. Mediates CPEB3-accelerated mRNA deadenylation by binding to CPEB3 and recruiting CNOT7 which leads to target mRNA deadenylation and decay.|||Belongs to the BTG family.|||Cytoplasm|||Interacts with ERBB2. Interacts with CNOT7. Interacts with CPEB3 (via C-terminal RNA-binding region); recruits CNOT7 to CPEB3 to form a ternary complex required for mRNA deadenylation and decay. Interacts with CNOT8. Interacts with CPEB4.|||Nucleus|||Phosphorylated on Ser and Thr residues.|||Ubiquitous. http://togogenome.org/gene/10090:Araf ^@ http://purl.uniprot.org/uniprot/P04627 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Interacts with TH1L/NELFD.|||Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade (By similarity). Phosphorylates PFKFB2 (By similarity). http://togogenome.org/gene/10090:Fbxo10 ^@ http://purl.uniprot.org/uniprot/Q7TQF2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the SCF(FBXO10) complex consisting of CUL1, SKP1 and FBXO10. Interacts with BCL2. Interacts with PRDM1.|||Cytoplasm|||FBXO10 deletion has no detectable effect on B-cells in bone marrow or spleen. Similarly, it has no detectable effect on T-cell thymic development or T-cell splenic maturation.|||Particularly highly expressed in B-cells.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Mediates the ubiquitination and degradation of BCL2, an antiapoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. Targets also the receptor for advanced glycation end products RAGE for ubiquitination and subsequent lysosomal degradation. Directly controls HGAL/GCSAM ubiquitination and degradation and thereby decreases BCR signaling. http://togogenome.org/gene/10090:C9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J032|||http://purl.uniprot.org/uniprot/P06683 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complement C6/C7/C8/C9 family.|||Cell membrane|||Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9. About 20 C9 chains oligomerize to give rise to a huge beta-barrel that forms a 100 Angstrom diameter pore in target membranes.|||Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C9 is the pore-forming subunit of the MAC.|||Initially, positions and connectivity of disulfide bonds were based on peptide sequencing done for the human protein. The high-resolution crystal structure for the mouse protein corrected the positions and connectivities of some disulfide bonds (PubMed:30111885). The distance between Cys-55 and Cys-92 in the monomeric mouse protein precludes formation of a disulfide bond, contrary to what is seen in the structure of the human polymeric form of the protein (Probable).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Secreted|||Target cell membrane http://togogenome.org/gene/10090:Wnt3 ^@ http://purl.uniprot.org/uniprot/A2A649|||http://purl.uniprot.org/uniprot/P17553|||http://purl.uniprot.org/uniprot/Q3TQ59 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Wnt family.|||Detected at 6.25 to 7.5 dpc in primitive streak, proximal epiblast, visceral endoderm and at the junction between the embryonic and extraembryonic ectoderm, with higher levels in the posterior region (PubMed:10431240, PubMed:19841259). Detected in the ectoderm at forelimb buds at 9.5 dpc (PubMed:12569130). Detected in all outgrowing limbs and in ectoderm flanking the limbs at least till 11.5 dpc (PubMed:12569130). Highly expressed in embryos at 11.5 and 12.5 dpc, with very low expression levels before and after this period (PubMed:2162045).|||Detected at low levels in adult brain (PubMed:2162045). Dorsal portion of the neural tube, dorsal ectoderm, the branchial arches, and the limb buds.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Interacts with PORCN (PubMed:10866835). Interacts with WLS (PubMed:19841259).|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (By similarity). Required for normal gastrulation, formation of the primitive streak, and for the formation of the mesoderm during early embryogenesis (PubMed:10431240). Required for normal formation of the apical ectodermal ridge and for normal embryonic limb development (PubMed:12569130).|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||Some mouse mammary tumors induced by mouse mammary tumor virus (MMTV) contain a provirus integrated into a host cell region which has been named Wnt3.|||extracellular matrix http://togogenome.org/gene/10090:Ift70b ^@ http://purl.uniprot.org/uniprot/B2RXA2|||http://purl.uniprot.org/uniprot/Q9CY00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TTC30/dfy-1/fleer family.|||Interacts with the IFT B complex components IFT27, IFT46, IFT74, IFT52, IFT57, IFT80, IFT81 and IFT88 (PubMed:23810713). Interacts with KIF17 (PubMed:23810713).|||Required for polyglutamylation of axonemal tubulin. Plays a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip.|||cilium http://togogenome.org/gene/10090:Ccr1l1 ^@ http://purl.uniprot.org/uniprot/P51676 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in the spleen, liver and leukocytes.|||Probable receptor for a C-C type chemokine. http://togogenome.org/gene/10090:Mrps15 ^@ http://purl.uniprot.org/uniprot/Q9DC71 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS15 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins (By similarity). Interacts with METTL17 (PubMed:31487196).|||Mitochondrion matrix http://togogenome.org/gene/10090:Nrg2 ^@ http://purl.uniprot.org/uniprot/D3YZR2 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the neuregulin family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Batf3 ^@ http://purl.uniprot.org/uniprot/Q9D275 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AP-1 family transcription factor that controls the differentiation of CD8(+) thymic conventional dendritic cells in the immune system. Acts via the formation of a heterodimer with JUN family proteins that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3' and regulates expression of target genes. Required for development of CD8-alpha(+) classical dendritic cells (cDCs) and related CD103(+) dendritic cells that cross-present antigens to CD8 T-cells and produce interleukin-12 (IL12) in response to pathogens.|||Belongs to the bZIP family.|||Heterodimer; heterodimerizes with JUN family proteins. Interacts with JUN.|||Highly expressed in CD8-alpha(+) classical dendritic cells (cDCs), with low to absent expression in other immune cells and non-immune tissues.|||Nucleus|||Selective loss of CD8-alpha(+) classical dendritic cells (cDCs) and CD103(+) dendritic cells, without abnormalities in other hematopoietic cell types or architecture. Dendritic cells are defective in cross-presentation, and mice lack virus-specific CD8(+) T-cell responses to West Nile virus. Mice also show reduced priming of CD8 T-cells after pulmonary Sendai virus infection, with increased pulmonary inflammation. Mice are extremely susceptible to T.gondii infection, with decreased production of interleukin-12 (IL12) and interferon-gamma. In contrast, mice are more resistant to L.monocytogenes infection.|||The increased protection toward L.monocytogenes infection in mice lacking Batf3 suggests that CD8-alpha(+) classical dendritic cells (cDCs) and CD103(+) dendritic cells are an entry point for infection by L.monocytogenes. http://togogenome.org/gene/10090:Mesp2 ^@ http://purl.uniprot.org/uniprot/O08574 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation ^@ Degraded by the proteasome.|||Down-regulated in NOTCH1, DLL1, RBPJ and FOXC1/FOXC2 mutant mice. Expression in the anterior presomitic mesoderm is periodic, dissipating once the segmental border is established. Negatively regulated by RIPPLY2. Positively regulated by TBX6 and Notch signaling.|||First transiently detected in the nascent mesoderm at the onset of gastrulation. A second site of expression is detected at 8 dpc in the rostral region of the presomitic mesoderm inmediately before segmentation. Down-regulated immediately after the formation of the segmented somites before 13.5 dpc. Initially expressed throughout the length of one somite, and then quickly repressed in the presumptive caudal region. Mesp2 is involved in the rapid down-regulation of its own expression in the presumptive caudal half of the somite.|||Mice die shortly after birth and show caudal truncation and severe skeletal malformations. Lack of segmentation and impaired segment polarity of the paraxial mesoderm are the primary defects. Mutants show altered expression of MEOX1, Pax1, and DLL1 and lack of expression of Notch1, Notch2, and FGFR1. Mice lacking Mesp1 and Mesp2 die around 9.5 dpc. The major defect is the apparent lack of any mesodermal layer between endoderm and ectoderm and a defect in the migratory activity of mesodermal cells.|||Nucleus|||Phosphorylated.|||Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm. May play a role with Tcf15 in the differentiation of myotomal and sclerotomal cells by regulating Pax family genes. Controls also the expression of the protocadherin PCDH8/PAPC, EPHA4, RIPPLY2, NOTCH2, FGFR1, and CER1. Binds to the E-boxes within the EPH4A and RIPPLY2 enhancers. http://togogenome.org/gene/10090:Trp53rkb ^@ http://purl.uniprot.org/uniprot/Q543M9 ^@ Similarity ^@ Belongs to the protein kinase superfamily. BUD32 family. http://togogenome.org/gene/10090:Pdk3 ^@ http://purl.uniprot.org/uniprot/Q4FJR4|||http://purl.uniprot.org/uniprot/Q922H2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PDK/BCKDK protein kinase family.|||Homodimer. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (By similarity).|||Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species (By similarity).|||Mitochondrion matrix http://togogenome.org/gene/10090:Espn ^@ http://purl.uniprot.org/uniprot/Q9ET47 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Expressed at high concentration in the microvillar parallel actin bundle (PAB) of hair cells stereocilia in the cochlea and vestibular system. Detected also at high levels of a number of other sensory cell types, including taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells. Isoforms 2, 3, 4 and 5 are expressed in Purkinje cells dendritic spines. Expressed in utricle hair bundles (at protein level) (PubMed:26926603).|||Jerker mice have a frameshift mutation that affect the espin C-terminus. This mutation cause deafness, vestibular dysfunction and hair cell degeneration.|||Monomer (Probable). Binds F-actin in a Ca(2+)-resistant fashion (PubMed:10588661). Interacts (via N-terminus) with BAIAP2 (via SH3-domain) (PubMed:12598619). Interacts with PFN2 (PubMed:15190118). Interacts with MYO3A (via C-terminus) (PubMed:26926603). Interacts with MYO3B (via C-terminus) (PubMed:26926603, PubMed:26785147).|||Multifunctional actin-bundling protein. Plays a major role in regulating the organization, dimension, dynamics and signaling capacities of the actin filament-rich microvilli in the mechanosensory and chemosensory cells (PubMed:14657236, PubMed:15190118). Required for the assembly and stabilization of the stereociliary parallel actin bundles. Plays a crucial role in the formation and maintenance of inner ear hair cell stereocilia (PubMed:21455486). Involved in the elongation of actin in stereocilia (PubMed:19287378, PubMed:22264607). In extrastriolar hair cells, required for targeting MYO3B to stereocilia tips, and for regulation of stereocilia diameter and staircase formation (PubMed:26926603).|||The WH2-domain binds actin monomer and mediates actin bundle assembly.|||cytoskeleton|||dendritic spine|||microvillus|||stereocilium http://togogenome.org/gene/10090:Ppil3 ^@ http://purl.uniprot.org/uniprot/Q9D6L8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the cyclophilin-type PPIase family. PPIL3 subfamily.|||Identified in the spliceosome C complex.|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. May be involved in pre-mRNA splicing (By similarity). http://togogenome.org/gene/10090:Map7d1 ^@ http://purl.uniprot.org/uniprot/A2AJI0|||http://purl.uniprot.org/uniprot/A2AJI1|||http://purl.uniprot.org/uniprot/A8Y5P4 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MAP7 family.|||The sequence differs from that shown because it is derived from pre-RNA.|||spindle http://togogenome.org/gene/10090:Cdc7 ^@ http://purl.uniprot.org/uniprot/Q9Z0H0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC7 subfamily.|||Forms a complex with either DBF4/DBF4A or DBF4B, leading to the activation of the kinase activity. Interacts with CLASPIN (via the acidic patch); the interaction is required for phosphorylation of MCM proteins and CLASPIN.|||Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN.|||Nucleus http://togogenome.org/gene/10090:Lactb ^@ http://purl.uniprot.org/uniprot/B2RWI2|||http://purl.uniprot.org/uniprot/Q9EP89 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S12 family.|||Down-regulated in a number of cancer cells.|||Expressed predominantly in liver.|||Mitochondrial serine protease that acts as a regulator of mitochondrial lipid metabolism (By similarity). Acts by decreasing protein levels of PISD, a mitochondrial enzyme that converts phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn), thereby affecting mitochondrial lipid metabolism (By similarity). It is unclear whether it acts directly by mediating proteolysis of PISD or by mediating proteolysis of another lipid metabolism protein (By similarity). Acts as a tumor suppressor that has the ability to inhibit proliferation of multiple types of cancer cells: probably by promoting decreased levels of PISD, thereby affecting mitochondrial lipid metabolism (PubMed:28329758).|||Mitochondrion http://togogenome.org/gene/10090:Calcoco2 ^@ http://purl.uniprot.org/uniprot/A2A6M5 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CALCOCO family.|||Dimer. Part of a complex consisting of CALCOCO2, TAX1BP1 and MYO6. Interacts with MYO6 (By similarity). Interacts with GEMIN4. Interacts with ATG8 family members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2. Interacts with ATG8 family member MAP1LC3C. Interacts with LGALS8. Interacts with TOM1; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and CALCOCO2 (By similarity). Interacts with AZI2 (By similarity).|||Expression is limited to the pluripotent cells of the early embryo and the germline. Expressed in blastocysts, epiblasts and purified primordial germ cells.|||The CLIR (LC3C-interacting region) motif is required for interaction with MAP1LC3C, but dispensable for CALCOCO2-mediated autophagosome maturation.|||The LGALS8-binding domain is essential for the recruitment to cytosol-exposed infecting bacteria.|||The LIR-like motif is required for interaction with MAP1LC3A, MAP1LC3B and GABARAPL2, as well as for CALCOCO2-mediated autophagosome maturation.|||Xenophagy-specific receptor required for autophagy-mediated intracellular bacteria degradation (By similarity). Acts as an effector protein of galectin-sensed membrane damage that restricts the proliferation of infecting pathogens upon entry into the cytosol by targeting LGALS8-associated bacteria for autophagy (By similarity). Initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen-containing autophagosome maturation (By similarity). Bacteria targeting to autophagosomes relies on its interaction with MAP1LC3A, MAP1LC3B and/or GABARAPL2, whereas regulation of pathogen-containing autophagosome maturation requires the interaction with MAP3LC3C (By similarity). May play a role in ruffle formation and actin cytoskeleton organization and seems to negatively regulate constitutive secretion (By similarity).|||autophagosome membrane|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Cercam ^@ http://purl.uniprot.org/uniprot/A3KGW5|||http://purl.uniprot.org/uniprot/B2RSF7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 25 family.|||Endoplasmic reticulum lumen|||Probable cell adhesion protein involved in leukocyte transmigration across the blood-brain barrier. Does not express any beta-galactosyltransferase activity in vitro. http://togogenome.org/gene/10090:Syt4 ^@ http://purl.uniprot.org/uniprot/P40749 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Expressed in many regions of the nervous system but is undetectable in extra neural tissues (PubMed:8058779).|||Interacts with KIF1A; the interaction increases in presence of calcium and decreases when SYT4 is phosphorylated at Ser-135.|||Phosphorylation at Ser-135 by MAPK8/JNK1 reduces interaction with KIF1A and neuronal dense core vesicles mobility.|||Synaptotagmin family member which does not bind Ca(2+) (By similarity). Involved in neuronal dense core vesicles (DCVs) mobility through its interaction with KIF1A. Upon increased neuronal activity, phosphorylation by MAPK8/JNK1 destabilizes the interaction with KIF1A and captures DCVs to synapses (PubMed:29166604). Plays a role in dendrite formation by melanocytes (By similarity).|||Synaptotagmin family member which does not bind Ca(2+). Plays a role in dendrite formation by melanocytes (By similarity).|||Unlike in other synaptotagmin family members, the first C2 domain/C2A does not bind Ca(2+) neither mediates Ca(2+)-dependent phospholipid binding. An aspartate-to-serine substitution in this domain inactivates Ca(2+)/phospho-lipid binding.|||neuronal dense core vesicle membrane http://togogenome.org/gene/10090:Pitpnm2 ^@ http://purl.uniprot.org/uniprot/Q6NS55|||http://purl.uniprot.org/uniprot/Q6ZPQ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.|||Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro). Binds calcium ions (By similarity).|||Detected in retina and in the dentate gyrus of the cerebellum.|||Endomembrane system|||Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with PTK2B via its C-terminus (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Snrnp35 ^@ http://purl.uniprot.org/uniprot/Q9D384 ^@ Subcellular Location Annotation|||Subunit ^@ Component of the U11/U12 snRNPs that are part of the U12-type spliceosome.|||Nucleus http://togogenome.org/gene/10090:Tcp10b ^@ http://purl.uniprot.org/uniprot/E9PYJ0|||http://purl.uniprot.org/uniprot/Q8C5S9 ^@ Similarity ^@ Belongs to the TCP10 family. http://togogenome.org/gene/10090:Rfwd3 ^@ http://purl.uniprot.org/uniprot/Q8CIK8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage. Plays a key role in RPA-mediated DNA damage signaling and repair. Acts by mediating ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and RAD51 at stalled replication forks, leading to remove them from DNA damage sites and promote homologous recombination. Also mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint. May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53.|||Interacts with MDM2 and p53/TP53. Binds to the RPA complex via direct interaction with RPA2. Interacts with RAD51.|||Mice are viable and do not show overt phenotypic abnormalities, although there is some evidence for increased embryonic lethality, earlier death, and subfertility, associated with testicular and ovarian atrophy in mutant. Mutant mice embryonic fibroblasts are hypersensitive to DNA cross-linking agents and show increased chromosomal breakage compared to controls.|||Nucleus|||PML body|||Phosphorylated at Ser-59 and Ser-75 upon DNA damage by ATM or ATR. ATM phosphorylation occurs at early times upon DNA damage, while ATR is the major kinase at later times. Phosphorylation by ATM and ATR is required to stabilize p53/TP53. Part of the phosphorylation depends upon RPA2 presence.|||The coiled coil domain may be involved in RPA2-binding. http://togogenome.org/gene/10090:Prss21 ^@ http://purl.uniprot.org/uniprot/Q9JHJ7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Could regulate proteolytic events associated with testicular germ cell maturation.|||Expressed in post-meiotic testicular germ cells.|||Testis. http://togogenome.org/gene/10090:Megf10 ^@ http://purl.uniprot.org/uniprot/Q6DIB5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MEGF family.|||Cell membrane|||Expressed in cerebellum (at protein level). Expressed in kidney, stellate cells of the cerebellum and macrophage cell lines.|||Expressed in embryo at 15 dpc (at protein level). Expressed in embryo at 8, 10, 11, 13, 14 and 15 dpc.|||Homomer (Probable). Interacts with GULP1 and ABCA1. Interacts with AP2M1. Does not interact with MEGF11 (By similarity). Binds with high affinity to complement C1q (By similarity). Interacts (via the cytoplasmic domain) with NOTCH1 (via NICD domain) (PubMed:28498977).|||Membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic cells. Receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells (PubMed:27170117). Cooperates with ABCA1 within the process of engulfment (By similarity). Promotes the formation of large intracellular vacuoles and may be responsible for the uptake of amyloid-beta peptides (PubMed:20828568). Necessary for astrocyte-dependent apoptotic neuron clearance in the developing cerebellum (PubMed:27170117). Plays a role in muscle cell proliferation, adhesion and motility. Is also an essential factor in the regulation of myogenesis. Controls the balance between skeletal muscle satellite cells proliferation and differentiation through regulation of the notch signaling pathway (PubMed:28498977, Ref.10). May also function in the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements (PubMed:22407321).|||Mutants show at postnatal day 7 an increased amount of apoptotic cells in the developing cerebellum. However, adult brains do not show higher numbers of apoptotic cells in the cerebellum compared to wild-type. Astrocytes from knockout mice as well as heterozygous mice have a significant impairment in engulfment of apoptotic cells (PubMed:27170117). Reduced proliferation of primary myoblasts (Ref.10). Mutants have normal mobility and their skeletal muscles show mildly increased endomysial connective tissue. They display reduced motor activity after exercise and show slower muscle regeneration (PubMed:28498977). MEGF10 and DMD double knockout animals have pronounced fiber size variability and intracellular inclusions in the quadriceps femoris with extensive endomysial connective tissue infiltration. Mice develop muscle weakness, kyphosis and a waddling gait. At 2 months of age, they have reduced contractile force compared to wild-type mice. They display reduced motor activity after exercise and they walk shorter distances than wild-type. They have a delayed regeneration after muscle injury and an aberrant muscle fber typing and cross-sectional areas (PubMed:28498977).|||Phosphorylated on tyrosine residues. Phosphorylation at Tyr-1030 may be important for muscle cell proliferation.|||The EMI and EGF-like domains work in concert to promote self-assembly.|||Ubiquitinated; mono- and polyubiquitinated forms are detected.|||phagocytic cup http://togogenome.org/gene/10090:Ppp4r3b ^@ http://purl.uniprot.org/uniprot/Q922R5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMEK family.|||Cytoplasm|||Nucleus|||Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4). May regulate the activity of PPP4C at centrosomal microtubule organizing centers (By similarity).|||Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complex PPP4C-PPP4R2-PPP4R3B.|||centrosome http://togogenome.org/gene/10090:Lce1b ^@ http://purl.uniprot.org/uniprot/Q9D149 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Gimap1 ^@ http://purl.uniprot.org/uniprot/Q3TFI6 ^@ Similarity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily. http://togogenome.org/gene/10090:Cptp ^@ http://purl.uniprot.org/uniprot/Q8BS40 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GLTP family.|||Cell membrane|||Endosome membrane|||Mediates the intracellular transfer of ceramide-1-phosphate (C1P) between organelle membranes and the cell membrane. Required for normal structure of the Golgi stacks. Can bind phosphoceramides with a variety of aliphatic chains, but has a preference for lipids with saturated C16:0 or monounsaturated C18:1 aliphatic chains, and is inefficient with phosphoceramides containing lignoceryl (C24:0). Plays a role in the regulation of the cellular levels of ceramide-1-phosphate, and thereby contributes to the regulation of phospholipase PLA2G4A activity and the release of arachidonic acid. Has no activity with galactosylceramide, lactosylceramide, sphingomyelin, phosphatidylcholine, phosphatidic acid and ceramide. C1P transfer is stimulated by phosphatidylserine in C1P source vesicles (By similarity). Regulates autophagy, inflammasome mediated IL1B and IL18 processing, and pyroptosis, but not apoptosis (PubMed:29164996).|||Nucleus outer membrane|||cytosol|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ugt1a7c ^@ http://purl.uniprot.org/uniprot/Q6ZQM8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||Endoplasmic reticulum membrane|||Homodimer. Homooligomer. Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers.|||UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous estrogen hormone epiestradiol. Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties. Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II. Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan.|||Widely expressed with highest levels detected in colon and kidney. http://togogenome.org/gene/10090:Dusp11 ^@ http://purl.uniprot.org/uniprot/Q6NXK5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Monomer. May interact with SFRS7 and SFRS9/SRP30C.|||Nucleus|||Nucleus speckle|||Possesses RNA 5'-triphosphatase and diphosphatase activities, but displays a poor protein-tyrosine phosphatase activity. In addition, has phosphatase activity with ATP, ADP and O-methylfluorescein phosphate (in vitro). Binds to RNA. May participate in nuclear mRNA metabolism. http://togogenome.org/gene/10090:Lrig2 ^@ http://purl.uniprot.org/uniprot/Q52KR2 ^@ Miscellaneous|||Subcellular Location Annotation ^@ Cell membrane|||Cytoplasm|||May be due to a competing acceptor splice site. http://togogenome.org/gene/10090:Slc30a6 ^@ http://purl.uniprot.org/uniprot/J3QMX8|||http://purl.uniprot.org/uniprot/Q8BJM5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Expressed in brain and liver, and to a lower extent also in lung. Highly expressed in brain (at protein level).|||Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway (Probable). As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis (By similarity).|||Heterodimer with SLC30A5; form a functional zinc ion transmembrane transporter.|||Hydrophilic histidine residues that participate to zinc binding in transporters of the family are not conserved in SLC30A6.|||Membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ttll13 ^@ http://purl.uniprot.org/uniprot/A4Q9F6 ^@ Domain|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the tubulin--tyrosine ligase family.|||Gln-208 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in heart and testis (PubMed:17499049). Expressed in brain, kidney, liver, lung, muscle and trachea (PubMed:17499049). In the brain, expressed in ependymal cilia, cortex, corpus callosum and striatum (PubMed:23897886).|||Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin (PubMed:17499049). Mediates ATP-dependent polyglutamate side-chain elongation of the polyglutamylation reaction but not the initiation step (PubMed:17499049). Preferentially modifies the alpha-tubulin tail over a beta-tail (PubMed:17499049).|||The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding. http://togogenome.org/gene/10090:Arl6ip6 ^@ http://purl.uniprot.org/uniprot/Q8BH07 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ARL6IP6 family.|||Contaminating sequence.|||Nucleus inner membrane http://togogenome.org/gene/10090:Adcy1 ^@ http://purl.uniprot.org/uniprot/O88444 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by calcium/calmodulin (PubMed:9662407). Activated by forskolin. Activated by the G protein alpha subunit GNAS. Inhibited by the G protein beta and gamma subunit complex. Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP.|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates responses to increased cellular Ca(2+)/calmodulin levels (PubMed:9662407, PubMed:7816821). May be involved in regulatory processes in the central nervous system (PubMed:9662407). May play a role in memory and learning (PubMed:7816821). Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (PubMed:24048828).|||Cell membrane|||Cytoplasm|||Expressed throughout inner ear development.|||Expression in the retina oscillates in a circadian manner.|||Interacts with CALM.|||Membrane|||Membrane raft|||Mice appear grossly normal and healthy, but have decreased levels of calmodulin-sensitive adenylyl cyclase activity in the brain (PubMed:7816821). They show impaired spatial memory (PubMed:7816821). Mice show a significant reduction in daytime contrast sensitivity (PubMed:24048828).|||N-glycosylated.|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules. http://togogenome.org/gene/10090:Dusp2 ^@ http://purl.uniprot.org/uniprot/Q05922 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||By mitogens.|||Dephosphorylates both phosphorylated Thr and Tyr residues in MAPK1, and dephosphorylation of phosphotyrosine is slightly faster than that of phosphothreonine (PubMed:16288922). Can dephosphorylate MAPK1 (PubMed:16288922).|||In hematopoietic tissues such as spleen and thymus.|||Interacts with MAPK14; this interaction does not lead to catalytic activation of DUSP2 and dephosphrylation of MAPK14.|||Nucleus http://togogenome.org/gene/10090:Sugt1 ^@ http://purl.uniprot.org/uniprot/Q9CX34 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SGT1 family.|||Cytoplasm|||May play a role in ubiquitination and subsequent proteasomal degradation of target proteins.|||Nucleus|||Phosphorylated at Ser-252 and Ser-302, dephosphorylation promotes nuclear translocation, most likely due to disruption of the SUGT1-HSP90 complex.|||Probably associates with SCF (SKP1-CUL1-F-box protein) complex through interaction with SKP1. Interacts with S100A6. Interacts with HSP90 (By similarity).|||The CS domain mediates interaction with HSP90. http://togogenome.org/gene/10090:Serpina9 ^@ http://purl.uniprot.org/uniprot/Q9D7D2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Secreted http://togogenome.org/gene/10090:Efhd1 ^@ http://purl.uniprot.org/uniprot/Q9D4J1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a calcium sensor for mitochondrial flash (mitoflash) activation, an event characterized by stochastic bursts of superoxide production (By similarity). May play a role in neuronal differentiation (PubMed:16336229).|||In the cerebral cortex, at birth, confined in the Purkinje cell layer (PCL) and in cerebellar nuclei. Not detected in the external germinal layer (EGL). At P5 and P10, predominantly found in the PCL and internal germinal layer (IGL). Not detected in the EGL. At P10 and P20, up-regulated. At P20, expression similar to that of the adult cerebellum.|||Mitochondrion inner membrane|||Widely expressed (PubMed:16336229). Highest expression in testis, followed by ovary, kidney, cerebrum, cerebellum, heart, liver, and spleen (PubMed:12270117). In the cerebrum and cerebellum, undetectable at embryonic stages, expression increases after birth up to adult stage (PubMed:12270117). In adult CNS, detected in neurons of the cerebellum, cerebrum and hippocampus formation, including dentate gyrus and Cornu Ammonis, but not in the white matter (PubMed:12270117). In the testis, expressed in spermatocytes, but not in spermatogonia nor in interstitial cells (PubMed:12270117). In ovary, found predominantly in mural granulosa cells and those of the cumulus oophorus (PubMed:12270117). In kidney, expressed in collecting ducts, but not in glomeruli (PubMed:12270117). Not detected in skeletal muscle (PubMed:12270117). http://togogenome.org/gene/10090:Bud23 ^@ http://purl.uniprot.org/uniprot/Q148S9|||http://purl.uniprot.org/uniprot/Q9CY21 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. BUD23/WBSCR22 family.|||Cytoplasm|||Heterodimer with TRMT112; this heterodimerization is necessary for the metabolic stability and activity of the catalytic subunit BUD23. Interacts with GRIP1.|||May be ubiquitinated and targeted to degradation in response to pro-inflammatory cytokine signaling.|||Nucleus|||S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the N(7) position of a guanine in 18S rRNA. Requires the methyltransferase adapter protein TRM112 for full rRNA methyltransferase activity. Involved in the pre-rRNA processing steps leading to small-subunit rRNA production independently of its RNA-modifying catalytic activity. Important for biogenesis end export of the 40S ribosomal subunit independent on its methyltransferase activity. Locus-specific steroid receptor coactivator. Potentiates transactivation by glucocorticoid (NR3C1), mineralocorticoid (NR3C2), androgen (AR) and progesterone (PGR) receptors. Required for the maintenance of open chromatin at the TSC22D3/GILZ locus to facilitate NR3C1 loading on the response elements. Required for maintenance of dimethylation on histone H3 'Lys-79' (H3K79me2), although direct histone methyltransferase activity is not observed in vitro.|||nucleoplasm|||perinuclear region http://togogenome.org/gene/10090:C5ar1 ^@ http://purl.uniprot.org/uniprot/P30993 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasmic vesicle|||Homodimer. May also form higher-order oligomers. Interacts (when phosphorylated) with ARRB1 and ARRB2; the interaction is associated with internalization of C5aR.|||Phosphorylated on serine residues in response to C5a binding, resulting in internalization of the receptor and short-term desensitization to C5a.|||Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a. The ligand interacts with at least two sites on the receptor: a high-affinity site on the extracellular N-terminus, and a second site in the transmembrane region which activates downstream signaling events. Receptor activation stimulates chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production.|||Sulfation plays a critical role in the association of C5aR with C5a, but no significant role in the ability of the receptor to transduce a signal and mobilize calcium in response to a small peptide agonist. http://togogenome.org/gene/10090:Ttll2 ^@ http://purl.uniprot.org/uniprot/A4Q9E4 ^@ Domain|||Function|||Similarity|||Tissue Specificity ^@ Arg-175 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Belongs to the tubulin--tyrosine ligase family.|||Highly expressed in brain, kidney, liver and testis (PubMed:17499049). Expressed in heart, lung, muscle and spleen (PubMed:17499049).|||Probable tubulin polyglutamylase that generates side chains of glutamate on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of target proteins (PubMed:17499049). Similar to TTLL1, may acquire enzymatic activity only in complex with other proteins as it is most likely lacking domains important for autonomous activity (By similarity). Probably involved in the side-chain initiation step of the polyglutamylation reaction rather than the elongation step (Probable). http://togogenome.org/gene/10090:Ctsr ^@ http://purl.uniprot.org/uniprot/Q497X4|||http://purl.uniprot.org/uniprot/Q9JIA9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Expressed in adult but not in embryo.|||Lysosome|||Placenta. http://togogenome.org/gene/10090:Spata21 ^@ http://purl.uniprot.org/uniprot/Q8BHW6 ^@ Function ^@ Involved in the differentiation of haploid spermatids. http://togogenome.org/gene/10090:Tmem120b ^@ http://purl.uniprot.org/uniprot/Q3TA38 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM120 family.|||Expressed in inguinal and subcutaneous white adipose tissue and in brown adipose tissue.|||Heterooligomer with TMEM120A.|||Necessary for efficient adipogenesis (PubMed:26024229). Does not show ion channel activity (PubMed:32084332).|||Nucleus inner membrane|||Up-regulated during adipocyte differentiation. http://togogenome.org/gene/10090:Gpr21 ^@ http://purl.uniprot.org/uniprot/Q8BX79 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Vasp ^@ http://purl.uniprot.org/uniprot/P70460 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Ena/VASP family.|||Cytoplasm|||Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation (By similarity).|||Expressed constantly throughout brain development, with lower levels in adulthood.|||Highly expressed in thymus and spleen. Lower levels in lung, ovary, placenta and fat.|||Homotetramer (By similarity). Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This interaction is important for targeting to focal adhesions and the formation of actin-rich structures at the apical surface of cells. Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal SH3 domain of DNMBP. Interacts weakly with MEFV (By similarity).|||Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser-153, the preferred site for PKG, Ser-235. In ADP-activated platelets, phosphorylation by PKA or PKG/PRKG1 on Ser-153 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-274 requires prior phosphorylation on Ser-153 and Ser-235. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-274 by AMPK does not require prior phosphorylation at Ser-153 or Ser-235. Phosphorylation at Ser-153 by PKA is required for localization to the tight junctions in epithelial cells. Phosphorylation modulates F-actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-318 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-153, while nitric oxide (NO) promotes phosphorylation at Ser-153, but also at Ser-235.|||The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.|||The WH1 domain mediates interaction with XIRP1.|||cytoskeleton|||filopodium membrane|||focal adhesion|||lamellipodium membrane|||tight junction http://togogenome.org/gene/10090:Slc2a12 ^@ http://purl.uniprot.org/uniprot/B2RRB2|||http://purl.uniprot.org/uniprot/Q8BFW9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.|||Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Cell membrane|||Endomembrane system|||Expressed in skeletal muscle, heart, brain, kidney, spleen, adipose tissues and to a lesser extent in small intestine and lung.|||Expression is clearly detected in ovulated oocytes and 2-cells embryos but decline day 3 morulae. Remains at very low levels between 2 dpc and 11 dpc.|||Insulin-independent facilitative glucose transporter.|||perinuclear region http://togogenome.org/gene/10090:Ankrd2 ^@ http://purl.uniprot.org/uniprot/Q9WV06 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed at 9.5 dpc, with a pattern of expression that shows restricted localization to the myotome of somites. By 13.5 dpc, expression is observed within intercostal and back muscles. At 14.5 dpc and 15.5 dpc, expression is observed in tail myotomal muscles, and in intervertebral and back muscles. Hybridization was also detected within limb muscles. This pattern of expression was maintained at least up until 17.5 dpc. No localization within the heart.|||Expressed by myoblasts (at protein level). Expressed in skeletal and cardiac muscles.|||Functions as a negative regulator of myocyte differentiation. May interact with both sarcoplasmic structural proteins and nuclear proteins to regulate gene expression during muscle development and in response to muscle stress.|||I band|||Interacts with ID3; both proteins cooperate in myoblast differentiation. Interacts with TTN/titin (By similarity). Interacts (via ANK repeats) with TCAP; the interaction is direct (By similarity). Interacts with TJP1 (via PDZ domains) (By similarity). Interacts with PML; the interaction is direct (By similarity). Interacts with p53/TP53 (By similarity). Interacts with YBX1 (By similarity). Interacts with AKT2.|||Nucleus|||PML body|||Phosphorylation at Ser-68 by PKB/AKT2 in response to oxidative stress induces translocation to the nucleus and negatively regulates myoblast differentiation.|||Up-regulated in response to mechanical stretch of skeletal muscle (hypertrophy mechanically-induced).|||cytosol http://togogenome.org/gene/10090:Cyp2d10 ^@ http://purl.uniprot.org/uniprot/P24456 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Bclaf3 ^@ http://purl.uniprot.org/uniprot/A2AG58 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BCLAF1/THRAP3 family.|||Mitochondrion http://togogenome.org/gene/10090:Mob1b ^@ http://purl.uniprot.org/uniprot/Q8BPB0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activator of LATS1/2 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Stimulates the kinase activity of STK38L (By similarity).|||Belongs to the MOB1/phocein family.|||Binds STK38L. Interacts with LATS1 and LATS2 (By similarity).|||Cytoplasm|||Nucleus|||Phosphorylated by STK3/MST2 and STK4/MST1 and this phosphorylation enhances its binding to LATS1. http://togogenome.org/gene/10090:Vmn1r43 ^@ http://purl.uniprot.org/uniprot/Q8VIC9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Map1a ^@ http://purl.uniprot.org/uniprot/Q9QYR6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3 different light chains, LC1, LC2 and LC3, can associate with MAP1A and MAP1B proteins. Interacts with guanylate kinase-like domain of DLG1, DLG2 and DLG4. Binds to CSNK1D (By similarity). Interacts with TIAM2. MAP1 light chain LC2: Interacts with ELAVL4 (PubMed:21288476).|||Belongs to the MAP1 family.|||Both isoforms highly expressed in brain, and to a lesser extent in embryo. Isoform 1 is also expressed at a low level in other tissues including heart and muscle.|||LC2 is generated from MAP1A by proteolytic processing. It is free to associate with both MAP1A and MAP1B (By similarity).|||Phosphorylated by CSNK1D.|||Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements.|||The basic region containing the repeats may be responsible for the binding of MAP1A to microtubules.|||cytoskeleton http://togogenome.org/gene/10090:Carm1 ^@ http://purl.uniprot.org/uniprot/Q9WVG6 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9 dpc, expression is prominent in the neural tube and somites.|||Auto-methylated on Arg-551. Methylation enhances transcription coactivator activity. Methylation is required for its role in the regulation of pre-mRNA alternative splicing.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.|||Chromosome|||Cytoplasm|||Homodimer (PubMed:17882261, PubMed:19897492). Interacts with NR1H4 (By similarity). Interacts with SNRPC (By similarity). Interacts with the C-terminus of NCOA2/GRIP1, NCO3/ACTR and NCOA1/SRC1 (PubMed:10381882). Part of a complex consisting of CARM1, EP300/P300 and NCOA2/GRIP1 (PubMed:11997499). Interacts with FLII, TP53, myogenic factor MEF2, EP300/P300, TRIM24, CREBBP and CTNNB1 (PubMed:14966289, PubMed:15186775, PubMed:11713257, PubMed:16322096, PubMed:11997499, PubMed:11701890, PubMed:11983685, PubMed:19843527). Interacts with RELA (PubMed:15616592). Identified in a complex containing CARM1, TRIM24 and NCOA2/GRIP1 (PubMed:16322096). Interacts with NCOA3/SRC3 (PubMed:19843527). Interacts with SKP2 (PubMed:30366907). Interacts (via PH domain-like fold) with C9orf72 (PubMed:30366907). Interacts with PARP1; promoting PARP1 recruimtent to replication forks (By similarity).|||Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability (PubMed:10381882, PubMed:21138967, PubMed:11341840, PubMed:11997499, PubMed:19897492, PubMed:14966289, PubMed:17218272). Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activates transcription via chromatin remodeling (PubMed:10381882, PubMed:11747826, PubMed:12498683, PubMed:11751582, PubMed:11341840, PubMed:11997499, PubMed:15339660, PubMed:15616592). During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription (PubMed:11997499, PubMed:16322096, PubMed:17882261, PubMed:19843527). During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C (PubMed:11713257). During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B (PubMed:11983685). Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue (PubMed:18188184). Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors (PubMed:21138967). Also seems to be involved in p53/TP53 transcriptional activation (PubMed:15186775). Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation (PubMed:11701890). Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs (PubMed:11850402, PubMed:12756295, PubMed:12237300). Acts as a transcriptional coactivator of ACACA/acetyl-CoA carboxylase by enriching H3R17 methylation at its promoter, thereby positively regulating fatty acid synthesis (PubMed:30366907). Independently of its methyltransferase activity, involved in replication fork progression: promotes PARP1 recruitment to replication forks, leading to poly-ADP-ribosylation of chromatin at replication forks and reduced fork speed (By similarity).|||Methylation of H3R17 (H3R17me) by CARM1 is stimulated by preacetylation of H3 'Lys-18' (H3K18ac) H3 'Lys-23' (H3K23ac) by EP300 and blocked by citrullination of H3 'Arg-17' (H3R17ci) by PADI4.|||Neonatal lethality. The lungs of neonates do not inflate and they do not breathe. The same neonate lethality is observed with mutants that produce CARM1 protein without enzyme activity. Embryos are distinctly smaller at 18.5 dpc. They show reduced lipid accumulation in brown adipose tissue and reduced amounts of brown adipose tissue. Thymocyte differentiation is blocked at an early stage. Mutants display complete loss of protein methylation of the CARM1 substrates PABPC1 and EP300/P300.|||Nucleus|||Phosphorylation at Ser-217 is strongly increased during mitosis, and decreases rapidly to a very low, basal level after entry into the G1 phase of the cell cycle (By similarity). Phosphorylation at Ser-217 interferes with S-adenosyl-L-methionine binding and strongly reduces methyltransferase activity. Phosphorylation at Ser-217 may promote cytosolic location (PubMed:19843527).|||Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO9 at Lys-228; leading to proteasomal degradation.|||Ubiquitously expressed. Within the brain, present in proliferating cells from lateral ventricular zone and dentate gyrus (at protein level). http://togogenome.org/gene/10090:Cacna2d1 ^@ http://purl.uniprot.org/uniprot/A0A411ACY8|||http://purl.uniprot.org/uniprot/O08532|||http://purl.uniprot.org/uniprot/Q14BH8 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel subunit alpha-2/delta family.|||Binds gabapentin, an antiepileptic drug.|||Cell membrane|||Dimer formed of alpha-2-1 and delta-1 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (By similarity).|||Isoform 2A is expressed in skeletal muscle and aorta. Isoform 2B is expressed in brain. Isoform 2C is expressed in heart. Isoform 2D is expressed in heart and smooth muscle. Isoform 2E is expressed in smooth muscle. All five isoforms are expressed in the cardiovascular system.|||Membrane|||Proteolytically processed into subunits alpha-2-1 and delta-1 that are disulfide-linked.|||The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.|||The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (By similarity). Plays an important role in excitation-contraction coupling (By similarity). http://togogenome.org/gene/10090:Flg2 ^@ http://purl.uniprot.org/uniprot/Q2VIS4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the S100-fused protein family.|||Cytoplasm|||Cytoplasmic granule|||Deiminated by PADI1, PADI2 or PADI3 in vitro. The deiminated form is degraded by calpain-1/CAPN1 more quickly and into shorter peptides than the intact protein.|||Essential for normal cell-cell adhesion in the cornified cell layers. Important for proper integrity and mechanical strength of the stratum corneum of the epidermis.|||In the N-terminal section; belongs to the S-100 family.|||May be processed by calpain-1/CAPN1. http://togogenome.org/gene/10090:Vmn1r58 ^@ http://purl.uniprot.org/uniprot/G3X9U3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chst3 ^@ http://purl.uniprot.org/uniprot/O88199 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.|||Golgi apparatus membrane|||Mice are viable through adulthood. In their spleen the level of chondroitin 6'-sulfate is almost undetectable. In the spleen of 5-6 week-old mice, the number of CD62L(+)CD44(low) T-lymphocytes corresponding to naive T-lymphocytes is significantly decreased, whereas those in other secondary lymphoid organs are unchanged.|||N-glycosylated.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin (PubMed:9597547, PubMed:11696535). Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices (PubMed:9597547). Catalyzes with a lower efficiency the sulfation of Gal residues of keratan sulfate, another glycosaminoglycan (PubMed:11696535). Can also catalyze the sulfation of the Gal residues in sialyl N-acetyllactosamine (sialyl LacNAc) oligosaccharides (By similarity). May play a role in the maintenance of naive T-lymphocytes in the spleen (PubMed:11696535).|||Widely expressed. Highly expressed in spleen, lung, eye and stomach. Constitutively expressed at low level during the mid- to late-gestation period. Expressed in the brain in a temporally controlled manner: peaks at 2 weeks after birth in the cerebellum, but at 3 weeks in the cerebrum. Localizes to stromal cells in the bone marrow, and stromal cells in the marginal zone and red pulp of the spleen, but the sense probe did not. http://togogenome.org/gene/10090:Eef2kmt ^@ http://purl.uniprot.org/uniprot/Q3UZW7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. EEF2KMT family.|||Catalyzes the trimethylation of eukaryotic elongation factor 2 (EEF2) on 'Lys-525'.|||Cytoplasm|||Interacts with FAM86B2 and FAM86C1P. http://togogenome.org/gene/10090:Gm7592 ^@ http://purl.uniprot.org/uniprot/A0A668KLT6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rnaset2a ^@ http://purl.uniprot.org/uniprot/C0HKG5|||http://purl.uniprot.org/uniprot/C0HKG6|||http://purl.uniprot.org/uniprot/Q5FWA0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RNase T2 family.|||Endoplasmic reticulum lumen|||Inhibited by Zn(2+) and Cu(2+).|||Lysosome lumen|||Mitochondrion intermembrane space|||Ribonuclease that plays an essential role in innate immune response by recognizing and degrading RNAs from microbial pathogens that are subsequently sensed by TLR8. Cleaves preferentially single-stranded RNA molecules between purine and uridine residues, which critically contributes to the supply of catabolic uridine and the generation of purine-2',3'-cyclophosphate-terminated oligoribonucleotides. In turn, RNase T2 degradation products promote the RNA-dependent activation of TLR8. Also plays a key role in degradation of mitochondrial RNA and processing of non-coding RNA imported from the cytosol into mitochondria. Participates as well in degradation of mitochondrion-associated cytosolic rRNAs.|||Secreted http://togogenome.org/gene/10090:Setd5 ^@ http://purl.uniprot.org/uniprot/Q5XJV7 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to a report, lacks histone methyltransferase activity and regulates chromatin by interacting with HDAC3 and PAF1 complex (PAF1C) complex (PubMed:30455454). According to another publication, displays histone methyltransferase activity and directly trimethylates 'Lys-36' of histone H3 (H3K36me3) (PubMed:31515109).|||Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission (PubMed:30455454, PubMed:31515109). May act by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential to allow on-time RNA elongation dynamics (PubMed:31515109). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (PubMed:22939622). The relevance of histone methyltransferase activity is however subject to discussion (PubMed:27864380, PubMed:30455454).|||Chromosome|||Interacts with components of the PAF1 complex (PAF1C) such as LEO1, CTR9 and CDC73 (PubMed:27864380). Interacts with NCOR1 (PubMed:27864380). Interacts with HDAC3 (PubMed:30455454).|||Mid-gestation lethality due to severe developmental delay such as vascular abnormalities in the embryo and placenta, reduced cellular proliferation and increased apoptosis (PubMed:27864380). Defects are probably due to a widespread impairment in the regulation of gene expression (PubMed:27864380). Setd5-haploinsufficient mice display altered neuronal network connectivity leading to autistic-like behaviors (PubMed:30655503, PubMed:30455454, PubMed:31515109). Haploinsufficient Setd5 cortical neurons show reduced synaptic density and neuritic outgrowtho, with corresponding decreases in network activity and synchrony by electrophysiology (PubMed:30655503). Haploinsufficient mice display several autism-like behaviors, including hyperactivity, cognitive deficit, and altered social interactions (PubMed:30455454, PubMed:31515109, PubMed:30655503).|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Ankrd13d ^@ http://purl.uniprot.org/uniprot/Q6PD24 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with EGFR (ubiquitinated); the interaction is direct and may regulate EGFR internalization.|||Late endosome|||Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane (By similarity). http://togogenome.org/gene/10090:Trpv5 ^@ http://purl.uniprot.org/uniprot/P69744 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by WNK3.|||Apical cell membrane|||Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV5 sub-subfamily.|||Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:12077127, PubMed:14679186). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (PubMed:14679186). The channel is activated by low internal calcium level and the current exhibits an inward rectification. A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (PubMed:12077127). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).|||Detected in kidney cortex (at protein level).|||Glycosylated.|||Homotetramer and probably heterotetramer with TRPV6. Interacts with TRPV6 (PubMed:12574114). Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane (PubMed:12660155). Interacts with calmodulin (PubMed:15123711). Interacts with BSPRY, which results in its inactivation (PubMed:16380433).|||Mutant mice appear grossly normal and are fertile. They display polyuria and increased urinary excretion of Ca(2+), due to defective Ca(2+) reabsorption in the kidney distal convoluted tubules. Likewise, they display increased urinary excretion of phosphate. Besides, their urine has a lower pH. The polyuria and the urine acidification may be a response to the high urinary Ca(2+) levels, preventing the formation of kidney stones (PubMed:14679186). Serum Ca(2+) and phosphate levels are normal, probably due to increased expression of TRPV6 and increased Ca(2+) absorption in the intestine. The increased expression of TRPV6 may be due to the increased serum levels of 1,25-dihydroxy-vitamin D3 that are observed in mutant mice (PubMed:14679186, PubMed:27102152). Age-related changes in trabecular and cortical bone mass are accelerated in male mutant mice, including reduced trabecular and cortical bone thickness. Still, this has no effect on bone strength (PubMed:27102152). http://togogenome.org/gene/10090:Rock2 ^@ http://purl.uniprot.org/uniprot/F8VPK5|||http://purl.uniprot.org/uniprot/P70336|||http://purl.uniprot.org/uniprot/Q3TR46 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by RHOA binding. Inhibited by Y-27632 (By similarity).|||Activated by RHOA binding. Inhibited by Y-27632.|||An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization.|||Autophosphorylated. Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cell membrane|||Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.|||Cytoplasm|||Expression oscillates in a circadian manner in the aorta.|||Highly expressed in brain, heart, lung, liver, stomach, spleen, kidney, testis, muscle, embryo and placenta. Isoform 2 is expressed predominantly in the skeletal muscle.|||Homodimer (By similarity). Interacts with IRS1. Interacts with RAF1 (By similarity). Interacts with RHOA (activated by GTP), RHOB and RHOC (By similarity). Interacts with PPP1R12A (By similarity). Interacts with EP300 (By similarity). Interacts with CHORDC1 (By similarity). Interacts with BRCA2 (By similarity). Interacts with NPM1; this interaction enhances ROCK2 activity (By similarity). Interacts with SORL1 (By similarity). Interacts with PJVK (PubMed:28089576).|||Homodimer.|||Membrane|||Mice exhibit both EOB (eyes open at birth) and omphalocele phenotypes as a result of disorganization of actomyosin cables in the eyelid epithelium and defective actin assembly in the umbilical ring. Mice are impaired in both basal synaptic transmission and hippocampal long-term potentiation (LTP). Embryos manifest extensive thrombus formation in the placenta, resulting in placental dysfunction, intrauterine growth retardation, and fetal death.|||Nucleus|||Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.|||Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays a role in placental homeostasis during the perinatal period. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.|||centrosome http://togogenome.org/gene/10090:Atp5md ^@ http://purl.uniprot.org/uniprot/Q78IK2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the ATP synthase complex/complex V which is composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). The ATP synthase complex/complex V exists as a monomeric and a dimeric supercomplex that helps shape mitochondrial cristae to optimize proton flow (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. ATP5MK is a minor subunit of the mitochondrial membrane ATP synthase required for dimerization of the ATP synthase complex and as such regulates ATP synthesis in the mitochondria.|||Mitochondrion membrane http://togogenome.org/gene/10090:Sec31a ^@ http://purl.uniprot.org/uniprot/Q3UPL0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat SEC31 family.|||COPII is composed of at least 5 proteins: the SEC23/24 complex, the SEC13/31 complex and SAR1. SEC13 and SEC31 make a 2:2 tetramer that forms the edge element of the COPII outer coat. The tetramer self-assembles in multiple copies to form the complete polyhedral cage. Interacts (via WD 8) with SEC13 (By similarity). Interacts with PDCD6; interaction takes place in response to cytosolic calcium increase and leads to bridge together the BCR(KLHL12) complex and SEC31A, leading to monoubiquitination. Interacts with KLHL12 (By similarity).|||COPII-coated vesicle membrane|||Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER) (By similarity). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Monoubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex, leading to regulate the size of COPII coats.|||The ALG-2-binding site motif-2 (ABS-2) contains a PXPGF sequence that binds hydrophobic pocket 3 of PDCD6. http://togogenome.org/gene/10090:Btaf1 ^@ http://purl.uniprot.org/uniprot/E9QAE3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Nr1i3 ^@ http://purl.uniprot.org/uniprot/O35627|||http://purl.uniprot.org/uniprot/Q5FW96 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element (By similarity).|||Composed by a short N-terminal domain followed by the DNA binding, hinge, and ligand binding/dimerization domains.|||Cytoplasm|||Does not seem to act as a transactivator. Lacks the C-terminal portion of the ligand binding/dimerization domain.|||Heterodimer of NR1I3 and RXR. Interacts with PSMC4. Interacts with ECT2. Directly interacts with DNAJC7; this complex may also include HSP90. Interacts with CRY1 (PubMed:28751364). Interacts with CRY2 in a ligand-dependent manner (PubMed:28751364).|||Nucleus|||Phosphorylated at Thr-48 by PKC, dephosphorylation of Thr-48 is required for nuclear translocation and activation.|||Predominantly expressed in liver.|||cytoskeleton http://togogenome.org/gene/10090:Ccin ^@ http://purl.uniprot.org/uniprot/Q8CDE2 ^@ Function|||Subcellular Location Annotation ^@ Possible morphogenetic cytoskeletal element in spermiogenic differentiation.|||calyx http://togogenome.org/gene/10090:Or6d12 ^@ http://purl.uniprot.org/uniprot/Q7TS33|||http://purl.uniprot.org/uniprot/Q8C0U2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrch2 ^@ http://purl.uniprot.org/uniprot/Q3UMG5 ^@ Function|||Sequence Caution ^@ Intron retention.|||May play a role in the organization of the cytoskeleton. http://togogenome.org/gene/10090:Kifc2 ^@ http://purl.uniprot.org/uniprot/G3X8Q6 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. http://togogenome.org/gene/10090:Slc22a19 ^@ http://purl.uniprot.org/uniprot/Q8VCA0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Sodium-independent organic anion transporter which shows high specificity for estrone sulfate, dehydroepiandrosterone sulfate, and the mycotoxin ochratoxin A (OTA) (PubMed:15068970, PubMed:16150593). Transport of OTA is strongly inhibited by estrone sulfate and probenecid, and to a lesser extent by 2,4-dichlorophenoxyacetic acid (2,4-D) and salicylate (PubMed:15068970). Transport of estrone sulfate is inhibited by various steroid sulfate conjugates including dehydroepiandrosterone sulfate, alpha-naphthyl sulfate, beta-estradiol sulfate, 4-methylumbelliferyl sulfate and p-nitrophenyl sulfate (but not minoxidil sulfate) (PubMed:16150593).|||Specifically expressed in kidney, where it localizes to proximal tubules of the outer medulla (at protein level) (PubMed:15068970, PubMed:16150593). Not detected in other tissues tested (PubMed:15068970). http://togogenome.org/gene/10090:Vmn1r104 ^@ http://purl.uniprot.org/uniprot/L7N293 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem161b ^@ http://purl.uniprot.org/uniprot/A0A286YCA7|||http://purl.uniprot.org/uniprot/Q8C2L6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM161 family.|||Cell membrane|||Essential for maintaining normal cardiac rhythm in the developing heart and for neonatal survival (PubMed:33597309). Inhibits potassium and calcium currents in the cardiomyocytes, this assists in timely action potential repolarization and thereby maintains normal cardiac rhythm (PubMed:33597309).|||Knockout mice are perinatal lethal and isolated embryonic cardiomyocytes exhibit arrhythmic calcium oscillations.|||Membrane http://togogenome.org/gene/10090:Ncbp3 ^@ http://purl.uniprot.org/uniprot/Q8BZR9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. NCBP3 serves as adapter protein linking the capped RNAs (m7GpppG-capped RNA) to NCBP1/CBP80. Unlike the conventional CBC with NCBP2 which binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus, the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role in only mRNA export. The alternative CBC is particularly important in cellular stress situations such as virus infections and the NCBP3 activity is critical to inhibit virus growth (PubMed:26382858).|||Belongs to the NCBP3 family.|||Component of an alternative cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3. Interacts with SRRT, KPNA3, THOC5 and EIF4A3.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Exoc8 ^@ http://purl.uniprot.org/uniprot/Q6PGF7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EXO84 family.|||Cell projection|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Cytoplasm|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8 (By similarity). Interacts (via PH domain) with GTP-bound RALA and RALB (By similarity). Interacts with SH3BP1; required for the localization of both SH3BP1 and the exocyst to the leading edge of migrating cells (By similarity).|||growth cone|||perinuclear region http://togogenome.org/gene/10090:Ap1m1 ^@ http://purl.uniprot.org/uniprot/P35585|||http://purl.uniprot.org/uniprot/Q3UG16 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Interacts with MARCHF11 (By similarity).|||Belongs to the adaptor complexes medium subunit family.|||Golgi apparatus|||Phosphorylation of membrane-bound AP1M1/AP1M2 increases its affinity for sorting signals.|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Ccdc172 ^@ http://purl.uniprot.org/uniprot/Q810N9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC172 family.|||Cytoplasm|||May interact with TEKT2.|||cilium http://togogenome.org/gene/10090:Foxl1 ^@ http://purl.uniprot.org/uniprot/Q64731 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Deficient mice show postnatal growth retardation secondary to severe structural abnormalities of the stomach, duodenum, jejunum and decreased intestinal uptake of D-glucose and levels of the intestinal D-glucose transporter Slc5a1.|||Nucleus|||Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium. Target gene of the hedgehog (Hh) signaling pathway via GLI2 and GLI3 transcription factors. http://togogenome.org/gene/10090:Parp16 ^@ http://purl.uniprot.org/uniprot/Q7TMM8 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-mono-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Endoplasmic reticulum membrane|||In absence of activation signal, PARP16 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition.|||Interacts with KPNB1.|||Intracellular mono-ADP-ribosyltransferase that plays a role in different processes, such as protein translation and unfolded protein response (UPR), through the mono-ADP-ribosylation of proteins involved in those processes. Acts as an inhibitor of protein translation by catalyzing mono-ADP-ribosylation of ribosomal subunits, such as RPL14 and RPS6, thereby inhibiting polysome assembly and mRNA loading. Mono-ADP-ribosylation of ribosomal subunits is promoted by NMNAT2. Involved in the unfolded protein response (UPR) by ADP-ribosylating and activating EIF2AK3 and ERN1, two important UPR effectors. May also mediate mono-ADP-ribosylation of karyopherin KPNB1 a nuclear import factor. May not modify proteins on arginine or cysteine residues compared to other mono-ADP-ribosyltransferases.|||The PARP alpha-helical domain (also named HD region) is regulatory, it packs against the catalytic domain. http://togogenome.org/gene/10090:Zfp24 ^@ http://purl.uniprot.org/uniprot/Q91VN1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ According to PubMed:20080941, most mice die by postnatal day 25 (P25) due to myelination defects. Brains and spinal cords isolated from P14 mice appear to be smaller than those from wild-type mice and to lack white matter. Mutant oligodendrocytes arrest at a late stage of differentiation. Expression of genes expressed specifically in mature myelinating oligodendrocytes is down-regulated. According to PubMed:17064688, embryos are severely retarded in development and die at approximately 7.5 dpc. One possible explanation for the different phenotypes described is that the two null alleles are not identical. In the mutants described by PubMed:20080941, the PGK-neo cassette used for positive selection of embryonic stem (ES) cells has been removed, whereas it remains in the allele described by PubMed:17064688.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||In the embryo, barely detectable at day 17, peaks at day 11 and remains constant thereafter. Detected early during embryogenesis in ectodermal, endodermal, mesodermal and extraembryonic tissues. Expressed in the developing central nervous system. In the developing central nervous system (CNS), mainly expressed in progenitors.|||Nucleus|||Sumoylated.|||Transcription factor required for myelination of differentiated oligodendrocytes. Required for the conversion of oligodendrocytes from the premyelinating to the myelinating state. In the developing central nervous system (CNS), involved in the maintenance in the progenitor stage by promoting the cell cycle. Specifically binds to the 5'-TCAT-3' DNA sequence. Has transcription repressor activity in vitro.|||Widely expressed with highest levels in heart, brain, liver, skeletal muscle, kidney and testis and very low levels in spleen and lung. http://togogenome.org/gene/10090:Smarcc2 ^@ http://purl.uniprot.org/uniprot/Q6PDG5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMARCC family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:22952240, PubMed:26601204). May also interact with the SIN3A histone deacetylase transcription repressor complex in conjunction with SMARCA2 and SMARCA4. Interacts with SMARD1 (By similarity). Interacts with KDM6B (PubMed:21095589). Interaction with RCOR1 (By similarity). Interacts with DPF2 (By similarity). Interacts with ERCC6 (By similarity). Interacts with FOS (PubMed:29272704).|||Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5-16.5 dpc.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Can stimulate the ATPase activity of the catalytic subunit of these complexes. May be required for CoREST dependent repression of neuronal specific gene promoters in non-neuronal cells. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (PubMed:17640523). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (PubMed:28369036).|||Mono-ADP-ribosylation at Lys-312 by SIRT6 promotes recruitment to the enhancer region of the Heme oxygenase-1 (HO-1) locus, leading to transcription activation of the locus.|||Nucleus|||SMARCD2 knockout mice show aberrant hematopoiesis, characterized by defective myeloid and erythroid differentiation, a reduction in granulocyte/macrophage progenitors as well as reduced neutrophil granulocytes and monocytes. Knockout embryos die late during fetal development and are characterized by reduced size, pallor, and decreased temporal vascularization. http://togogenome.org/gene/10090:Mgat4c ^@ http://purl.uniprot.org/uniprot/Q9D306 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 54 family.|||Glycosyltransferase that participates in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N-linked glycans. Catalyzes the formation of the GlcNAcbeta1-4 branch on the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans. Essential for the production of tri- and tetra-antennary N-linked sugar chains. Does not catalyze the transfer of GlcNAc to the Manalpha1-6 arm to form GlcNAcBeta1-4Manalpha1-6 linkage ('GnT-VI' activity) (By similarity).|||Golgi apparatus membrane http://togogenome.org/gene/10090:Ptk2 ^@ http://purl.uniprot.org/uniprot/P34152 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.|||Cell membrane|||Cytoplasm|||Detected in neonate myocardium; levels are low directly after birth but high five to fifteen days after birth, and not detectable in adults.|||Does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription (By similarity).|||Embryonically lethal. Embryos die at about 8.5 dpc, despite normal implantation. Embryos do not develop a normal head fold, neural tube or heart tube. Endothelial-specific gene disruption is lethal at about 11 dpc, due to defects in embryonic angiogenesis.|||Interacts with GIT1. Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase activity-dependent) (By similarity). Interacts with MISP (By similarity). Interacts with PIAS1. Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream signaling pathways. Interacts with P53/TP53. Interacts with STAT1. Interacts with WASL. Interacts with ARHGEF7. Interacts with DCC. Interacts (via first Pro-rich region) with CAS family members (via SH3 domain), including BCAR1, BCAR3 and CASS4. Interacts with NEDD9 (via C-terminus) (PubMed:25059660). Interacts with SORBS1. Interacts with ARHGEF28. Interacts with SHB. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (By similarity). Interacts with PXN and TLN1. Interacts with TGFB1I1. Interacts with PIK3R1 or PIK3R2. Interacts with SRC, GRB2 and GRB7. Interacts with LPXN (via LD motif 3). Interacts with CD36. Interacts with EMP2; regulates PTK2 activation and localization (By similarity). Interacts with DSCAM (PubMed:22685302). Interacts with AMBRA1 (PubMed:28362576). Interacts (when tyrosine-phosphorylated) with tensin TNS1; the interaction is increased by phosphorylation of TNS1 (By similarity).|||Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:25059660). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1.|||Nucleus|||Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-925, even when cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21. Phosphorylation on tyrosine residues is enhanced by NTN1 (PubMed:22685302).|||Produced by alternative promoter usage.|||Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop by SRC. Phosphorylation at Tyr-397, Tyr-576 and Tyr-577 is required for maximal kinase activity.|||Sumoylated; this enhances autophosphorylation.|||The C-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.|||The first Pro-rich domain interacts with the SH3 domain of CAS family members, such as BCAR1 and NEDD9.|||a stop codon in position 912 which was translated as Trp to extend the sequence.|||cell cortex|||centrosome|||cilium basal body|||cytoskeleton|||focal adhesion|||perinuclear region http://togogenome.org/gene/10090:Eomes ^@ http://purl.uniprot.org/uniprot/O54839 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Embryonic lethal due to peri-implantation defects. Mutant embryos arrest soon after implantation and fail to form organized embryonic or extraembryonic structures. Conditional mutants, with expression abrogated in the inner cell mass of embryos from early implantation stages onward, display gastrulation defects.|||Expressed in CD8+ T-cells.|||Functions as a transcriptional activator playing a crucial role during development. Functions in trophoblast differentiation and later in gastrulation, regulating both mesoderm delamination and endoderm specification. Plays a role in brain development being required for the specification and the proliferation of the intermediate progenitor cells and their progeny in the cerebral cortex. Also involved in the differentiation of CD8+ T-cells during immune response regulating the expression of lytic effector genes.|||Nucleus|||Originally expressed in the trophoectoderm of the blastocyst and later in the extraembryonic ectoderm of the early post-implantation embryo. In the embryo proper, expressed in the posterior part of the epiblast. During gastrulation, extends distally into the primitive streak and nascent mesoderm. Also expressed in the developing forebrain and the olfactory lobes. Expressed at 12.5 dpc and 14.5 dpc in the forebrain.|||Up-regulated in CD8+ T-cells upon activation. http://togogenome.org/gene/10090:Vmn2r36 ^@ http://purl.uniprot.org/uniprot/K7N741 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gfi1b ^@ http://purl.uniprot.org/uniprot/O70237 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated by IL6 treatment in myelomonocytic cells, and in response to EPO in myeloid cells; EPO-induced down-regulation of Gfi1b is STAT5-dependent.|||Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages. Component of a RCOR-GFI-KDM1A-HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. Transcriptional repressor or activator depending on both promoter and cell type context; represses promoter activity of SOCS1 and SOCS3 and thus, may regulate cytokine signaling pathways. Cooperates with GATA1 to repress target gene transcription, such as the apoptosis regulator BCL2L1; GFI1B silencing in leukemic cell lines markedly increase apoptosis rate. Inhibits down-regulation of MYC and MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells. Represses expression of GATA3 in T-cell lymphomas and inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 and GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells. Suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction. Binds to gamma-satellite DNA and to its own promoter, auto-repressing its own expression. Alters histone methylation by recruiting histone methyltransferase to target genes promoters. Plays a role in heterochromatin formation.|||Expressed in bone marrow and in spleen. Detected in hematopoietic stem cells, erythroblasts, and megakaryocytes. Expressed in thymocytes.|||Interacts with histone methyltransferases EHMT2 and SUV39H1. Interacts with ARIH2 (via RING-type 2) and with RUNX1T1 (By similarity). Forms a complex with GATA1. Component of a RCOR-GFI-KDM1A-HDAC complex. Interacts directly with RCOR1, KDM1A and HDAC2.|||Methylation at Lys-8 in the SNAG domain seems required for the recruitment of the corepressor complex.|||Mice are not viable and embryos die by 15 dpc during the transition from primitive to definitive hematopoiesis. They exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce enucleated erythrocytes. Their fetal liver contains erythroid and megakaryocytic precursor arrested in their development.|||Nucleus|||The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.|||The zinc finger domain is essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain.|||Transgenic mice with insertion of green fluorescence protein (GFP) cDNA in Gfi1b gene allowed to show up-regulation of Gfi1b in early stage of B-cell and in a subset of early thymic pre-T-cell. Mice overexpressing Gfi1b display peripheral T-lymphopenia and a profound defect in activation after CD3 cross-linking. Spleen cells show reduction in the numbers of CD4 and CD8 T-cells. Thymocyte lineage commitment and maturation are altered. http://togogenome.org/gene/10090:Klf8 ^@ http://purl.uniprot.org/uniprot/Q8BLM0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Interacts with corepressor CtBP2. Interacts with PIAS1, PIAS2, and PIAS4; the interaction with each ligase sumoylates KLF8 (By similarity).|||Nucleus|||Sumoylation at Lys-64 represses transcriptional activity and reduces cell cycle progression into the G(1) phase. Has no effect on subcellular location.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF8, the motif is inactive.|||Transcriptional repressor and activator. Binds to CACCC-boxes promoter elements. Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G(1) phase as a downstream target of focal adhesion kinase (FAK) (By similarity). http://togogenome.org/gene/10090:Pggt1b ^@ http://purl.uniprot.org/uniprot/Q8BUY9 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the protein prenyltransferase subunit beta family.|||Binds 1 zinc ion per subunit.|||Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B (By similarity).|||Heterodimer of FNTA and PGGT1B. PGGT1B mediates interaction with substrate peptides (By similarity). http://togogenome.org/gene/10090:Cdh5 ^@ http://purl.uniprot.org/uniprot/P55284 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins (By similarity). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types (By similarity). This cadherin may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions (PubMed:9220534, PubMed:20332120). It associates with alpha-catenin forming a link to the cytoskeleton (By similarity). Acts in concert with KRIT1 and PALS1 to establish and maintain correct endothelial cell polarity and vascular lumen (PubMed:27466317). These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B (By similarity). Required for activation of PRKCZ and for localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction (By similarity).|||Cell junction|||Cell membrane|||Expressed in endothelial cells of allantois/umbilical vessels at 8.5 dpc (at protein level). During hemangioblast differentiation, expressed in hemogenic endothelium cells and down-regulated in nascent blood precursors.|||Expressed in postnatal endothelial cells of the retinal vascular plexus (at protein level).|||Interacts (via cadherin 5 domain) with PTPRB (PubMed:12234928). Interacts with TRPC4 (By similarity). Interacts with KRIT1 (By similarity). Interacts with PARD3 (PubMed:20047332). Interacts with RTN4 (isoform B) (By similarity). Interacts with PALS1; the interaction promotes PALS1 localization to cell junctions and is required for CDH5-mediated vascular lumen formation and endothelial cell polarity (PubMed:27466317).|||O-glycosylated.|||Phosphorylated on tyrosine residues by KDR/VEGFR-2. Dephosphorylated by PTPRB.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||Up-regulated by SOX7. http://togogenome.org/gene/10090:Mki67 ^@ http://purl.uniprot.org/uniprot/E9PVX6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates during the late G1 stage in the nucleus and maximum expression is found during G2 phase and mitosis (PubMed:8834799). During male meiosis, present in nuclei of all stages from the spermatogonium through spermatocytes I and II up to the earliest spermatid stage (early round spermatids) and then fades out (PubMed:12355204). Not detected in later spermatid stages or sperm (PubMed:12355204). During female meiosis, present in prophase I oocytes of fetal ovaries, while it is absent in resting oocytes. Reappears in oocytes of growing follicles and is continuously present up to metaphase II (at protein level) (PubMed:12355204).|||Chromosome|||Interacts with KIF15 (By similarity). Interacts (via the FHA domain) with NIFK (By similarity). Interacts with PPP1CC (By similarity). Component of a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5; the complex is formed as a result of interactions between components of a nuclear receptor-mediated transcription complex and a histone methylation complex (By similarity). Interacts with ZNF335 (By similarity).|||Mainly present in proliferating cells (at protein level).|||No visible phenotype. Mice were born at the expected Mendelian ratio and show no overt phenotype (PubMed:26949251). Cells do not show proliferation defects, but chromatin organization is impaired, with defects in heterochromatin compaction and long-range genomic interactions (PubMed:26949251).|||Nucleus|||Phosphorylated. Hyperphosphorylated in mitosis. Hyperphosphorylated form does not bind DNA.|||Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). Associates with the surface of the mitotic chromosome, the perichromosomal layer, and covers a substantial fraction of the chromosome surface (PubMed:27362226). Prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (By similarity). Does not contribute to the internal structure of mitotic chromosomes (PubMed:26949251). May play a role in chromatin organization (PubMed:26949251). It is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in maintaining mitotic chromosomes dispersed.|||Was thought to play a key role in cell proliferation, and is commonly used as a marker of cell proliferation. However, its primary function is uncoupled from cell proliferation (PubMed:26949251). Required to maintain mitotic chromosomes dispersed by forming a steric and electrostatic charge barrier (PubMed:27362226).|||nucleolus http://togogenome.org/gene/10090:Dck ^@ http://purl.uniprot.org/uniprot/P43346|||http://purl.uniprot.org/uniprot/Q545E8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DCK/DGK family.|||Homodimer.|||Nucleus|||Phosphorylated and activated in vitro upon phosphorylation at Ser-74 by CSNK1D/CK1.|||Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine. http://togogenome.org/gene/10090:Etaa1 ^@ http://purl.uniprot.org/uniprot/Q5SVT3 ^@ Caution|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts (via RBM1 motif) with RPA1. Interacts (via RBM2 motif) with RPA2. Interacts (via the ATR-activation domain motif) with ATR.|||It is uncertain whether Met-1 or Met-10 is the initiator.|||Nucleus|||Phosphorylated by ATR.|||Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity. Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1. Probably only regulates a subset of ATR targets.|||The ATR-activation domain (AAD) motif is required to bind and activate ATR.|||The RBM1 (RPA1-binding, also named RPA70N-binding) motif mediates interaction with RPA1. The RBM2 (RPA2-binding, also named RPA32C-binding) motif mediates interaction with RPA2. http://togogenome.org/gene/10090:Scube2 ^@ http://purl.uniprot.org/uniprot/D3YVM9 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Grid1 ^@ http://purl.uniprot.org/uniprot/Q61627 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRID1 subfamily.|||Cell membrane|||Dimer (PubMed:27418511). Interacts (via extracellular N-terminal domain) with CBLN1 (via C1q domain), and more weakly with CBLN2 (PubMed:22220752, PubMed:27418511).|||Equally in forebrain and cerebellum.|||Postsynaptic cell membrane|||Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. http://togogenome.org/gene/10090:Tceal7 ^@ http://purl.uniprot.org/uniprot/A3KGA4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TFS-II family. TFA subfamily.|||Nucleus|||Plays a role in the negative regulation of NF-kappa-B signaling at the basal level by modulating transcriptional activity of NF-kappa-B on its target gene promoters. Associates with cyclin D1 promoter containing Myc E-box sequence and transcriptionally represses cyclin D1 expression. Regulates telomerase reverse transcriptase expression and telomerase activity in both ALT (alternative lengthening of telomeres)and telomerase-positive cell lines (By similarity). http://togogenome.org/gene/10090:Fam207a ^@ http://purl.uniprot.org/uniprot/P58468 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLX9 family.|||May be involved in ribosome biogenesis.|||nucleolus http://togogenome.org/gene/10090:Ypel2 ^@ http://purl.uniprot.org/uniprot/Q0VA86|||http://purl.uniprot.org/uniprot/Q65Z95 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the yippee family.|||Detected in testis, heart, brain, spleen, lung and liver.|||May interact with FAM168B.|||nucleolus http://togogenome.org/gene/10090:Tubb2b ^@ http://purl.uniprot.org/uniprot/B2RSN3|||http://purl.uniprot.org/uniprot/Q9CWF2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||Strong expression is detected in the developing cortex and peripheral nervous system, as well as in the adult cerebellum, hippocampus and olfactory bulb.|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. Plays a critical role in proper axon guidance in both central and peripheral axon tracts. Implicated in neuronal migration.|||cytoskeleton http://togogenome.org/gene/10090:Deaf1 ^@ http://purl.uniprot.org/uniprot/Q3TYJ5|||http://purl.uniprot.org/uniprot/Q80V49|||http://purl.uniprot.org/uniprot/Q9Z1T5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Exencephaly and skeletal abnormalities in the rib cage and cervical vertebrae but no presphenoid bone or cranial nerve defects. DEAF1 homozygous mice neonates die 100% of the time and DEAF1 heterozygous mice survived in a 2:1 ratio.|||Expressed at all stages of mammary gland development with slightly higher levels observed during pregnancy and lactation. At 4 weeks, expression levels of isoform 1 and isoform 2 do not differ in pancreatic lymph nodes of nonobese diabetic (NOD) mice compared to NOD.B10 mice which do not develop diabetes. However, at 12 weeks, expression of isoform 1 is down-regulated while expression of isoform 2 is up-regulated in NOD mice but not in NOD.B10. There is no difference in expression levels at 12 weeks in spleen.|||Homodimer (By similarity). Isoform 1 and isoform 2 may form a heterodimer. May interact with the corepressors NCOR1 and NCRO2 (By similarity). Identified in a complex with XRCC5 and XRCC6. Interacts (via the SAND domain) with the DNA-PK complex subunit XRCC6; the interaction is direct with XRCC6 and may be inhibited by DNA-binding (By similarity). Interacts with LMO4; LMO4 blocks export from nucleus. Interacts with LMO2 and CLIM2.|||May be phosphorylated by DNA-PK complex in a DNA independent manner (in vitro).|||Nucleus|||Transcription factor that binds to sequence with multiple copies of 5'-TTC[CG]G-3' present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) 5'-AGGGTTCACCGAAAGTTCA-3'. Activates the proenkephalin gene independently of promoter binding, probably through protein-protein interaction (By similarity). Regulates epithelial cell proliferation and side-branching in the mammary gland. Required for neural tube closure and skeletal patterning. Controls the expression of peripheral tissue antigens in pancreatic lymph nodes. Isoform 1 displays greater transcriptional activity than isoform 2. Isoform 2 may inhibit transcriptional activity of isoform 1 by interacting with it and retaining it in the cytoplasm. Transcriptional activator of EIF4G3 (By similarity). May also involved in behavior (PubMed:24726472).|||Ubiquitously expressed during embryogenesis, with higher expression in regions of the central nervous system, dorsal root ganglia, submandibular gland, epidermis and breast. In 12-week-old NOD mice, expression of isoform 2 is sevenfold higher in lymph node stromal elements than in T-cells and tenfold higher than in B-cells. http://togogenome.org/gene/10090:Entpd6 ^@ http://purl.uniprot.org/uniprot/Q3U0P5 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GDA1/CD39 NTPase family.|||Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner. Has a strong preference for nucleoside diphosphates, preferentially hydrolyzes GDP, IDP, and UDP, with slower hydrolysis of CDP, ITP, GTP, CTP, ADP, and UTP and virtually no hydrolysis of ATP. The membrane bound form might support glycosylation reactions in the Golgi apparatus and, when released from cells, might catalyze the hydrolysis of extracellular nucleotides.|||Cell membrane|||Golgi apparatus membrane|||N-glycosylated.|||Secreted|||Strongly and equally activated by either Ca(2+) or Mg(2+). http://togogenome.org/gene/10090:Hddc3 ^@ http://purl.uniprot.org/uniprot/Q9D114 ^@ Function|||Similarity ^@ Belongs to the MESH1 family.|||ppGpp hydrolyzing enzyme involved in starvation response. http://togogenome.org/gene/10090:Ltb ^@ http://purl.uniprot.org/uniprot/A0A0U5JAA2|||http://purl.uniprot.org/uniprot/P41155 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cytokine that binds to LTBR/TNFRSF3. May play a specific role in immune response regulation. Provides the membrane anchor for the attachment of the heterotrimeric complex to the cell surface.|||Heterotrimer of either two LTB and one LTA subunits or (less prevalent) two LTA and one LTB subunits.|||Membrane http://togogenome.org/gene/10090:Klb ^@ http://purl.uniprot.org/uniprot/Q99N32 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.|||Cell membrane|||Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 887. These domains are therefore predicted to be inactive.|||Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 to bind FGF21.|||Expression starts at 10.5 dpc in hepatocytes. Expressed in the acinar cells of the pancreas and cervical brown adipose tissue at 15.5 dpc. Expressed in white adipose tissue at 19.5 dpc. Up-regulated during preadipocyte differentiation into adipocytes (at protein level).|||Interacts with FGF19; this interaction is direct. Interacts (via C-terminus) with FGF21; this interaction is direct (By similarity). Interacts with FGFR1 and FGFR4.|||Mice are viable and fertile, but have an altered bile metabolism: they have increased CYP7A1 levels, secrete more bile acids and are resistant to cholesterol gallstone formation.|||Present in liver, muscle and white adipose tissue, but not in kidney (at protein level). Expressed in liver and pancreas, and at lower levels in skin, stomach, skeletal muscle, small intestine and lung. http://togogenome.org/gene/10090:Cmip ^@ http://purl.uniprot.org/uniprot/Q9D486 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with FLNA.|||Intron retention.|||Nucleus|||Plays a role in T-cell signaling pathway. http://togogenome.org/gene/10090:Lin9 ^@ http://purl.uniprot.org/uniprot/A0A0A6YVZ7 ^@ Similarity ^@ Belongs to the lin-9 family. http://togogenome.org/gene/10090:Adck2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1X6|||http://purl.uniprot.org/uniprot/Q6NSR3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. ADCK protein kinase family.|||Membrane|||The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr). http://togogenome.org/gene/10090:Arf3 ^@ http://purl.uniprot.org/uniprot/P61205|||http://purl.uniprot.org/uniprot/Q3U344 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||GTP-binding protein involved in protein trafficking; modulates vesicle budding and uncoating within the Golgi apparatus.|||GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.|||Golgi apparatus|||Interacts with PRKCABP. Interacts with PI4KB and NCS1/FREQ at the Golgi complex.|||perinuclear region http://togogenome.org/gene/10090:Mtch2 ^@ http://purl.uniprot.org/uniprot/A2AFW6|||http://purl.uniprot.org/uniprot/Q791V5|||http://purl.uniprot.org/uniprot/Q9D050 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Expressed in a wide variety of tissues. Predominant expressed in liver, kidney, heart, skeletal muscle and testis.|||Interacts with p15BID.|||Membrane|||Mice homozygous for a knockout allele exhibit abnormal mesoderm development, disorganized extraembryonic tissue, lack of amnion and chorion formation, decreased embryo size and lethality at around 7.5 dpc (PubMed:20436477). Conditional knockout in the liver decreases the sensitivity of mice to Fas-induced hepatocellular apoptosis and prevents the recruitment of tBID to liver mitochondria (PubMed:20436477). Conditional knockout in skeletal muscle results in increased mitochondrial mass and metabolism granting protection against diet-induced obesity (PubMed:26876167).|||Mitochondrion outer membrane|||Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane. Catalyzes insertion of proteins with alpha-helical transmembrane regions, such as signal-anchored, tail-anchored and multi-pass membrane proteins. Does not mediate insertion of beta-barrel transmembrane proteins (By similarity). Also acts as a receptor for the truncated form of pro-apoptotic BH3-interacting domain death agonist (p15 BID) and has therefore a critical function in apoptosis (PubMed:20436477, PubMed:26219591, PubMed:26876167, PubMed:30510213). Regulates the quiescence/cycling of hematopoietic stem cells (HSCs) (PubMed:20436477, PubMed:26219591, PubMed:26876167). Acts as a regulator of mitochondrial fusion, essential for the naive-to-primed interconversion of embryonic stem cells (ESCs) (PubMed:30510213). Acts as a regulator of lipid homeostasis and has a regulatory role in adipocyte differentiation and biology (PubMed:26876167, PubMed:28127879). http://togogenome.org/gene/10090:Il2rb ^@ http://purl.uniprot.org/uniprot/P16297 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||Cell membrane|||Cell surface|||Non-covalent dimer of an alpha and a beta subunit. IL2R exists in 3 different forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit). The high and intermediate affinity forms also associate with a gamma subunit. Interacts with SHB upon interleukin stimulation (By similarity).|||Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (By similarity).|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Trim7 ^@ http://purl.uniprot.org/uniprot/Q923T7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinates via 'Lys-63'-linked polyubiquitination.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||Deletion mutant protects mice from DNA virus infection.|||E3 ubiquitin-protein ligase that have both tumor-promoting and tumor-suppressing activities and functions in several biological processes including innate immunity, regulation of ferroptosis as well as cell proliferation and migration. Acts as an antiviral effector against multiple viruses by targeting specific viral proteins for ubiquitination and degradation including norovirus NTPase protein. Mechanistically, recognizes the C-terminal glutamine-containing motif generated by viral proteases that process the polyproteins and trigger their ubiquitination and subsequent degradation (PubMed:35972292). Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (By similarity). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of pro-inflammatory cytokines and type I interferon (PubMed:30928727). Also plays a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation. Mediates the ubiquitination of the SIN3-HDAC chromatin remodeling complex component BRMS1. Modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells by ubiquitinating NCOA4, leading to its degradation (PubMed:32126128).|||Forms homodimers. Interacts with GNIP2. Interacts with GYG1. Interacts with RNF187 (via C-terminus).|||Golgi apparatus|||Highly expressed in antigen-presenting cells.|||Nucleus|||Phosphorylated at Ser-106 by RPS6KA5/MSK1, which stimulates the ubiquitin ligase activity.|||The B30.2 domain mediates interaction with GYG.|||The coiled-coil region mediates homodimerization and heterodimerization. http://togogenome.org/gene/10090:Hand1 ^@ http://purl.uniprot.org/uniprot/Q64279 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription factors). Interacts with MDFIC. Interacts with SOX15; the interaction enhances HAND1-induced differentiation of trophoblast giant cells (PubMed:16759287).|||Phosphorylation by PLK4 disrupts the interaction with MDFIC and leads to translocation into the nucleoplasm, allowing dimerization and transcription factor activity.|||Present as a maternal transcript in the egg as well as during cleavage development before blastocyst formation. At 7.5 dpc, strongly expressed in all trophoblast cells (PubMed:16759287). Expression seen in the ectoplacental cone and extraembryonic mesodermal components of the amnion, allantois and visceral yolk sac. This high extraembryonic expression persists in the embryonic component of the placenta throughout development. In the embryo, expressed at 7.75 dpc in the lateral mesoderm along the entire length of the embryo as well as throughout the precardiogenic mesoderm. At 8.0 dpc, in the developing heart, expression becomes restricted to the rostral and caudal regions of the straight heart tube, which are fated to form the conotruncus and left ventricle, respectively. Symmetric expression is observed along the left-right axis in the caudal heart tube and lateral mesoderm. As cardiac looping occurs, the interrupted anterior-posterior patterning is maintained with expression in the future left, but not right ventricle. Expressed in the myocardium, but not in the endocardium, and specifically on the greater curvature of the looping heart which is opposed to the pericardium. After day 10.5 dpc, the high cardiac expression level declines abruptly. By 13.5 dpc, expression in the heart is restricted to the regions of valve formation. Besides the heart, expression becomes detectable in the gut at 9.0 dpc. At 10.0 dpc, expressed also in the lateral mesoderm and in the neural crest-derived branchial arches. At 10.5 dpc prominent expression in the gut, pharyngeal arches and in sympathetic ganglion primordia. At that stage, a low level of transient expression is seen in the distal posterior region of the limb bud. At 12 dpc expressed in the conceptus trophoblast giant cell layer in the placenta (PubMed:16759287). At 13.5 dpc expressed in neural crest derivatives, with abundant expression in the autonomic nervous system and adrenal medulla.|||Smooth muscle cells of the gut and adrenal tissue.|||Transcription factor that plays an essential role in both trophoblast giant cell differentiation and in cardiac morphogenesis (PubMed:9500551, PubMed:16759287). Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box) (PubMed:7791788). Acts as a transcriptional repressor of SOX15 (PubMed:16759287). In the adult, could be required for ongoing expression of cardiac-specific genes (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Defa20 ^@ http://purl.uniprot.org/uniprot/Q45VN2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Foxk2 ^@ http://purl.uniprot.org/uniprot/Q3UCQ1 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, expressed ubiquitously in the developing central nervous system. This pattern persists at 14.5 dpc and 16.5 dpc, with expression levels varying.|||Component of SIN3A-, but not SIN3B-, containing multiprotein complexes (PubMed:25402684). Interacts with DVL1, DVL2 (when phosphorylated) and DVL3; the interaction induces DVL2 nuclear translocation (By similarity). Interacts with SUDS3 (By similarity). Interacts with BAP1 (when phosphorylated); leading to recruit the PR-DUB complex and repress FOXK2 target genes (By similarity).|||Cytoplasm|||Expressed in a wide range of adult brain regions, namely the piriform cortex, the major islands of Calleja and cells lining the lateral ventricles, the bed nucleus of stria terminalis, the paraventricular thalamic nucleus, habenula and all structures of the hippocampus. Also present in the hypothalamus, cerebral cortex and in the Purkinje cell layer in the cerebellum. Additionally expressed in dopamine neurons of the substantia and more sparsely in the ventral tegmental area.|||Hyperphosphorylated during mitosis by CDK1 and, to a lower extent, CDK2. Phosphorylation at Ser-364 and Ser-419 affects stability by promoting degradation.|||Nucleus|||The C-terminal part of the DNA-binding domain may contribute to DNA recognition specificity.|||Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (PubMed:25402684, PubMed:29861159, PubMed:30700909). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:25402684, PubMed:29861159, PubMed:30700909). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (PubMed:30700909). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (PubMed:30700909). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (PubMed:30700909). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (PubMed:25402684). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (By similarity). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (By similarity). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (By similarity). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (By similarity). http://togogenome.org/gene/10090:Neto1 ^@ http://purl.uniprot.org/uniprot/Q8R4I7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Depressed long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, NMDAR-dependent spatial learning and memory. Rescued by the ampakine CX546 at physiological doses.|||Expressed only in brain. Present throughout the central nervous system. Highly expressed in the hippocampal CA3 region, olfactory bulb and tubercle, caudate putamen, and neocortex in the adult brain.|||Interacts with PLZ domains of DLG2, DLG3 and DLG4 via its C-terminal TRV domain. Interacts with GRIN2A and GRIN2B via its CUB domains.|||Involved in the development and/or maintenance of neuronal circuitry. Accessory subunit of the neuronal N-methyl-D-aspartate receptor (NMDAR) critical for maintaining the abundance of GRIN2A-containing NMDARs in the postsynaptic density. Regulates long-term NMDA receptor-dependent synaptic plasticity and cognition, at least in the context of spatial learning and memory.|||Membrane|||Observed restrictively in brain throughout embryonic and postnatal stages. Expression pattern in brain slightly changes from 13 dpc to postnatal day 21 (P21). Expressed in both cerebrum and cerebellum throughout P0 to P35. In the cerebrum expression reached a plateau at P14 while expression in the cerebellum remains constant throughout all postnatal stages.|||Postsynaptic density membrane http://togogenome.org/gene/10090:Flii ^@ http://purl.uniprot.org/uniprot/Q9JJ28 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Expressed in blastocyst.|||Flii deficiency causes lethality during early embryogenesis at a stage preceding gastrulation.|||Increases the percentage of focal complex positive cells.|||Interacts with actin, ACTL6A, NCOA2 and MYD88 (By similarity). Interacts with LRRFIP1 and LRRFIP2. Upon LPS stimulation, LRRFIP2 competes for MYD88-binding. LRRFIP1 constitutively blocks the interaction with MyD88, even in the absence of LPS (By similarity). Interacts with the nuclear receptors ESR1 and THRB (By similarity). Interacts with CARM1. Interacts with SGK3.|||May play a role as coactivator in transcriptional activation by hormone-activated nuclear receptors (NR) and acts in cooperation with NCOA2 and CARM1. Involved in estrogen hormone signaling (By similarity). Essential for early embryonic development. May play a role in regulation of cytoskeletal rearrangements involved in cytokinesis and cell migration, by inhibiting Rac1-dependent paxillin phosphorylation.|||Nucleus|||Up-regulated in response to wounding.|||centrosome|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Il17d ^@ http://purl.uniprot.org/uniprot/A0A0B4J1G4|||http://purl.uniprot.org/uniprot/Q8K4C4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-17 family.|||Secreted http://togogenome.org/gene/10090:Aurkaip1 ^@ http://purl.uniprot.org/uniprot/Q9DCJ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrion-specific ribosomal protein mS38 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins (By similarity). Interacts with Aurora-A.|||May act as a negative regulator of Aurora-A kinase, by down-regulation through proteasome-dependent degradation.|||Mitochondrion matrix|||Nucleus|||Ubiquitously expressed and especially highly expressed in heart, skeletal muscle and testis. http://togogenome.org/gene/10090:Pramel13 ^@ http://purl.uniprot.org/uniprot/Q9D2F1 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Rps6ka5 ^@ http://purl.uniprot.org/uniprot/Q3TUH8|||http://purl.uniprot.org/uniprot/Q8C050 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation at Ser-359, Thr-645 and Thr-764 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-211, Ser-375 and Ser-380 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-814, Ser-816 and Ser-822 in its own C-terminal region.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Enzyme activity requires the presence of both kinase domains.|||Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA5 associates with and phosphorylates the NF-kappa-B p65 subunit RELA. Interacts with CREBBP and EP300 (By similarity).|||Nucleus|||Ser-375 and Thr-645 phosphorylation is required for kinase activity. Ser-375 and Ser-211 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-359, Thr-645 and Thr-764 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-814, Ser-816 and Ser-822 by the N-terminal kinase domain (By similarity).|||Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (By similarity)(PubMed:11553624, PubMed:11909979, PubMed:16806820). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:16806820). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:11553624). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (By similarity). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (By similarity). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:15870105, PubMed:16517600). May also phosphorylate 'Ser-28' of histone H3 (PubMed:11441012, PubMed:15870105). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (By similarity). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (PubMed:18690222). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (PubMed:18690222). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (PubMed:12807421). Phosphorylates TRIM7 at 'Ser-106' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (By similarity).|||Ubiquitinated. http://togogenome.org/gene/10090:Mroh7 ^@ http://purl.uniprot.org/uniprot/A2AVR2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tgfb3 ^@ http://purl.uniprot.org/uniprot/Q3TRQ9|||http://purl.uniprot.org/uniprot/Q91YU7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Homodimer; disulfide-linked.|||Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.|||extracellular matrix http://togogenome.org/gene/10090:Csf3 ^@ http://purl.uniprot.org/uniprot/P09920|||http://purl.uniprot.org/uniprot/Q0VB73 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-6 superfamily.|||Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes.|||Monomer.|||O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Sox6 ^@ http://purl.uniprot.org/uniprot/P40645 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expression is dependent on SOX9.|||Expression is transiently increased during brown adipocyte differentiation.|||Highly expressed in testis.|||Homodimer (PubMed:32442410). Interacts with DAZAP2 (PubMed:14530442). May interact with CENPK (PubMed:10996314).|||Newborn mice display mild skeletal abnormalities (PubMed:11702786). Knockout mice also display increase in prematurely differentiated oligodendrocyte precursor cells in the motor neuron progenitor domain of the spinal tube at 11.5 dpc (PubMed:26525805). At 18.5 dpc the number and distribution of oligodendroglia are normal, however there is an increased number of differentiating oligodendrocytes (PubMed:26525805). Double knockout of Sox13 and Sox6 show an increase in oligodendrocyte precursor cells in the spinal tube at 11.5 dpc, at 18.5 dpc the number and distribution of oligodendroglia are normal but contain an increased number of differentiating cells (PubMed:26525805). Mice lacking both Sox5 and Sox6 develop a severe chondrodysplasia characterized by the virtual absence of cartilage: chondrogenic cells are largely arrested at the stage of chondrogenic mesenchymal condensations (PubMed:11702786). Embryos lacking Sox5 (homozygous knockout) and heterozygous for Sox6 live until birth and show severe growth plate chondrocyte defects (PubMed:14993235). Embryos lacking Sox6 (homozygous knockout) and heterozygous for Sox5 live until birth and show severe growth plate chondrocyte defects (PubMed:14993235).|||Nucleus|||Sumoylation inhibits the transcriptional activity.|||Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation (Probable). Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis (PubMed:9755172, PubMed:11702786). Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate (PubMed:11702786, PubMed:15529345, PubMed:26150426). Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes (PubMed:14993235, PubMed:26150426). Together with SOX5, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts (PubMed:14993235). Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube (PubMed:26525805). Binds to the gene promoter of MBP and acts as a transcriptional repressor (PubMed:26525805). http://togogenome.org/gene/10090:Pfas ^@ http://purl.uniprot.org/uniprot/Q5SUR0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Cytoplasm|||In the N-terminal section; belongs to the FGAMS family.|||Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate (By similarity). http://togogenome.org/gene/10090:Myoz1 ^@ http://purl.uniprot.org/uniprot/Q9JK37 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, expressed at significant levels in cardiac muscle with lower levels detected in skeletal muscle of tongue. At 15.5 dpc, cardiac expression is down-regulated and only weakly detected in atria, whereas skeletal muscle expression is more robust.|||Belongs to the myozenin family.|||Expressed primarily in skeletal muscle and specifically enriched in the gastrocnemius, which is composed predominantly of fast-twitch muscle fibers. Detected at lower levels in heart.|||Interacts with ACTN2, ACTN3, FLNA, FLNB, FLNC, LDB3, PPP3CA and TCAP. Interacts via its C-terminal region with MYOT.|||Myozenins may serve as intracellular binding proteins involved in linking Z-disk proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.|||Nucleus|||pseudopodium http://togogenome.org/gene/10090:Nek5 ^@ http://purl.uniprot.org/uniprot/Q7TSC3 ^@ Similarity ^@ Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. http://togogenome.org/gene/10090:Slc4a7 ^@ http://purl.uniprot.org/uniprot/F8VQC9|||http://purl.uniprot.org/uniprot/U3RF68 ^@ Similarity|||Subcellular Location Annotation ^@ Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Lateral cell membrane|||Membrane http://togogenome.org/gene/10090:Gga3 ^@ http://purl.uniprot.org/uniprot/A2A9W7|||http://purl.uniprot.org/uniprot/Q8BMI3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GGA protein family.|||Early endosome membrane|||Endosome membrane|||Membrane|||Monomer. Interacts with GGA1 and GGA2 (By similarity). Binds to clathrin and activated ARFs, such as ARF1, ARF5 and ARF6 (PubMed:11950392). Binds RABEP1 and RABGEF1. Interacts with the membrane proteins M6PR/CD-MPR and IGF2R/CI-MPR and the accessory proteins SYNRG, EPN4, NECAP1, NECAP2 and AFTPH/aftiphilin. Interacts with TSG101 and UBC. Interacts with ADRA2B. Interacts with NTRK1; the interaction is independent of NTRK1 activation and ubiquitination. Interacts (via VHS domain) with BACE1 (via DXXLL motif) (By similarity).|||Phosphorylated by CK2 and dephosphorylated by PP2A. Phosphorylation of GGA3 allows the internal DXXLL motif to bind the VHS domain and to inhibit the recognition of cargo signals (By similarity).|||Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif (By similarity).|||Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell surface. Involved in BACE1 transport and sorting as well as regulation of BACE1 protein levels. Regulates retrograde transport of BACE1 from endosomes to the trans-Golgi network via interaction through the VHS motif and dependent of BACE1 phosphorylation. Modulates BACE1 protein levels independently of the interaction between VHS domain and DXXLL motif through recognition of ubiquitination (By similarity). Key player in a novel DXXLL-mediated endosomal sorting machinery to the recycling pathway that targets NTRK1 to the plasma membrane (By similarity).|||Proteolytically cleaved during apoptosis by CASP3.|||Recycling endosome membrane|||The GAE domain binds accessory proteins regulating GGAs function.|||The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis (By similarity).|||The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif).|||The unstructured hinge region contains clathrin-binding and an autoinhibitory (DXXLL) motifs.|||Ubiquitinated.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Eef1akmt4 ^@ http://purl.uniprot.org/uniprot/P0DPE0 ^@ Function|||Similarity ^@ Belongs to the methyltransferase superfamily.|||Protein-lysine methyltransferase that efficiently catalyzes three successive methylations on 'Lys-36' in eukaryotic translation elongation factor 1 alpha (EEF1A1 or EEF1A2). http://togogenome.org/gene/10090:Irak3 ^@ http://purl.uniprot.org/uniprot/Q8K4B2 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Asn-306 is present instead of the conserved Asp which is expected to be an active site residue. Low level autophosphorylation activity has been reported in PubMed:12054681, while other authors describe this as an inactive kinase.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.|||Cytoplasm|||Expressed in inflamed lung macrophages (at protein level) (PubMed:29686383). Expressed in dendritic cells (at protein level) (PubMed:29686383). Highly expressed in liver and thymus and at lower levels in heart, brain, spleen and kidney (PubMed:12054681).|||In response to intranasal administration of IL33, lung inflammation is reduced compared to wild-type and is associated with low infiltration by inflammatory cells, especially granulocytes, a severe reduction in Th2-type cytokine secretion, including Il4, Il5 and Il13 in bronchial alveolar fluids, and reduced up-regulation of Il6, Csf3, Cxcl2 and Ccl5 mRNAs.|||Monomer (By similarity). Homodimer (By similarity). May interact with IRAK4 (when phosphorylated) (By similarity). Interacts (when phosphorylated at Thr-110) with PIN1 (via WW domain) in response to IL33-mediated (but not TLR4 ligand LPS) dendritic cell stimulation (PubMed:29686383).|||Nucleus|||Putative inactive protein kinase which regulates signaling downstream of immune receptors including IL1R and Toll-like receptors (PubMed:12150927, PubMed:12054681, PubMed:29686383). Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex (PubMed:12150927, PubMed:12054681). Upon IL33-induced lung inflammation, positively regulates expression of IL6, CSF3, CXCL2 and CCL5 mRNAs in dendritic cells (PubMed:29686383).|||The nucleotide binding domain binds ATP with low affinity. http://togogenome.org/gene/10090:Lzts3 ^@ http://purl.uniprot.org/uniprot/A2AHG0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LZTS3 family.|||Interacts (via C-terminus) with SHANK3 (via PDZ domain). Interacts (via coiled coil) with SIPA1L1. Can form homooligomers.|||May be involved in promoting the maturation of dendritic spines, probably via regulating SIPA1L1 levels at the postsynaptic density of synapses.|||Postsynaptic density|||Synapse|||cytoskeleton|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Fbxo25 ^@ http://purl.uniprot.org/uniprot/A0A1B0GRC8|||http://purl.uniprot.org/uniprot/Q3UYF5|||http://purl.uniprot.org/uniprot/Q9D2Y6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in all tissues tested, except striated muscle (at protein level). Expressed predominantly in the cerebral cortex, the hippocampus and the Purkinje cell layer of the brain. Intestine and kidney show also significant levels.|||Expressed in neuronal tissues of 14.5 dpc mice.|||Nucleus|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex consisting of FBXO25, SKP1, CUL1 and RBX1. Interacts directly with SKP1 and CUL1. Interacts (via C-terminus) with beta-actin (via N-terminus) (By similarity).|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. May play a role in accumulation of expanded polyglutamine (polyQ) protein huntingtin (HTT).|||The F-box is necessary for the interaction with SKP1. http://togogenome.org/gene/10090:Or14j5 ^@ http://purl.uniprot.org/uniprot/Q8VGF0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnf141 ^@ http://purl.uniprot.org/uniprot/Q99MB7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression was first detected at postnatal day 6, and reached the adult level between postnatal day 14 and 21.|||Isoform 1 is testis-specific. Isoform 2 is expressed in heart, brain, skeletal muscle, kidney, pancreas, lung, liver and testis. Isoform 3 is expressed in heart, liver, and kidney.|||May be involved in spermatogenesis.|||Membrane http://togogenome.org/gene/10090:Evx2 ^@ http://purl.uniprot.org/uniprot/P49749|||http://purl.uniprot.org/uniprot/Q6P7W9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the even-skipped homeobox family.|||Nucleus http://togogenome.org/gene/10090:Brinp2 ^@ http://purl.uniprot.org/uniprot/Q6DFY8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BRINP family.|||Inhibits neuronal cell proliferation by negative regulation of the cell cycle transition.|||Secreted|||Up-regulated upon differentiation into neuronal cells in the presence of retinoic acid and BDNF. Down-regulated upon differentiation into astroglial cells.|||Weakly expressed in embryonic stem (ES) cells. Strongly expressed in ES-derived neural stem cells (NSCs). http://togogenome.org/gene/10090:Gbf1 ^@ http://purl.uniprot.org/uniprot/Q6DFZ1 ^@ Subcellular Location Annotation ^@ trans-Golgi network http://togogenome.org/gene/10090:Gm45927 ^@ http://purl.uniprot.org/uniprot/B2M0S2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SCAMP family.|||Membrane http://togogenome.org/gene/10090:Tsg101 ^@ http://purl.uniprot.org/uniprot/Q3UCW0|||http://purl.uniprot.org/uniprot/Q61187 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with VPS37A, VPS37B and VPS37C. Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with DMAP1 (PubMed:10888872). Interacts with GMCL (PubMed:12927808). Interacts with ubiquitin, stathmin and AATF (By similarity). Interacts with HGS; the interaction mediates the association with the ESCRT-0 complex (PubMed:12802020). Interacts with GGA1 and GGA3. Interacts (via UEV domain) with PDCD6IP/AIP1. Interacts with VPS28, SNF8 and VPS36. Self-associates. Interacts with MVB12A; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts with CEP55; the interaction is required for cytokinesis (By similarity). Interacts with PDCD6. Interacts with LITAF (By similarity). Interacts with murine leukemia virus Gag polyprotein (via PSAP motif) (PubMed:15908698). Interacts with MGRN1 (PubMed:19703557). Interacts with ARRDC1; recruits TSG101 to the plasma membrane (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (By similarity).|||Cytoplasm|||Early endosome membrane|||Expressed at all stages of mammary gland development, but at lower rate at early and mid pregnancy. Expressed in 1-cell and 2-cell stage embryos.|||Late endosome membrane|||Midbody ring|||Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. Ubiquitination inactivates it, possibly by regulating its shuttling between an active membrane-bound protein and an inactive soluble form. Ubiquitination by MGRN1 requires the presence of UBE2D1.|||Nucleus|||The UEV domain is required for the interaction of the complex with ubiquitin.|||The coiled coil domain may interact with stathmin.|||Ubiquitous. Higher expression in brain and mammary gland. Lower expression in liver and tumoral tissues.|||centrosome http://togogenome.org/gene/10090:Nrp1 ^@ http://purl.uniprot.org/uniprot/P97333 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neuropilin family.|||Cell membrane|||Cytoplasm|||Homodimer, and heterodimer with NRP2 (By similarity). Binds PLXNB1 (By similarity). Interacts with FER (PubMed:20133938). Interacts with VEGFA (PubMed:26503042). Interacts with ABCB8/MITOSUR in mitochondria (By similarity).|||Knockout embryos display higher susceptibility to oxidative stress in endothelium cells located in the intersomitic vessels.|||Mitochondrion membrane|||Nervous system.|||Receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system (By similarity). Mediates the chemorepulsant activity of semaphorins (PubMed:26503042). Recognizes a C-end rule (CendR) motif R/KXXR/K on its ligands which causes cellular internalization and vascular leakage (By similarity). Binds to semaphorin 3A (SEMA3A), the PLGF-2 isoform of PGF, the VEGF165 isoform of VEGFA and VEGFB (By similarity). Coexpression with KDR results in increased VEGF165 binding to KDR as well as increased chemotaxis. Regulates VEGF-induced angiogenesis (By similarity). Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (PubMed:26503042). Regulates mitochondrial iron transport via interaction with ABCB8/MITOSUR (By similarity).|||The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding. F5/8 domains mediate the recognition and binding to R/KXXR/K CendR motifs. http://togogenome.org/gene/10090:Aph1a ^@ http://purl.uniprot.org/uniprot/Q6GTF1|||http://purl.uniprot.org/uniprot/Q8BVF7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APH-1 family.|||Component of the gamma-secretase complex.|||Endoplasmic reticulum membrane|||Full embryonic lethality. No live homozygous embryos are present after 11 dpc.|||Golgi stack membrane|||Membrane|||Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:15634781, PubMed:19369254). Required for normal gamma-secretase assembly (PubMed:15634781, PubMed:19369254). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable).|||Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors.|||The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PSENEN/PEN2. http://togogenome.org/gene/10090:Tex52 ^@ http://purl.uniprot.org/uniprot/Q3TTI8 ^@ Tissue Specificity ^@ Expressed in Testis. http://togogenome.org/gene/10090:Cxcl10 ^@ http://purl.uniprot.org/uniprot/P17515|||http://purl.uniprot.org/uniprot/Q548V9 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||By interferon gamma.|||CXCL10-deficient mice possess a significantly reduced or delayed infiltration of NK and HSV-1-specific CD8+ T cells into herpes virus-infected tissue. In consequence, the antiviral response is delayed.|||Expressed in the spleen, thymus, lymph nodes and liver (PubMed:8145049). Expressed in astrocytes, microglia, and neurons (PubMed:15456824).|||Monomer, dimer, and tetramer (PubMed:18560148). Interacts with CXCR3 (via N-terminus) (By similarity).|||Pro-inflammatory cytokine that is involved in a wide variety of processes such as chemotaxis, differentiation, and activation of peripheral immune cells, regulation of cell growth, apoptosis and modulation of angiostatic effects (By similarity) (PubMed:28623423). Plays thereby an important role during viral infections by stimulating the activation and migration of immune cells to the infected sites (PubMed:18624292, PubMed:19017990, PubMed:28468883). Mechanistically, binding of CXCL10 to the CXCR3 receptor activates G protein-mediated signaling and results in downstream activation of phospholipase C-dependent pathway, an increase in intracellular calcium production and actin reorganization. In turn, recruitment of activated Th1 lymphocytes occurs at sites of inflammation (By similarity). Activation of the CXCL10/CXCR3 axis also plays an important role in neurons in response to brain injury for activating microglia, the resident macrophage population of the central nervous system, and directing them to the lesion site. This recruitment is an essential element for neuronal reorganization (PubMed:15456824).|||Secreted http://togogenome.org/gene/10090:Grik5 ^@ http://purl.uniprot.org/uniprot/Q61626|||http://purl.uniprot.org/uniprot/Q80WU3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK5 subfamily.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.|||Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate = glutamate >> AMPA.|||Tetramer of two or more different subunits. Associates with GRIK1 (both edited and unedited versions), GRIK2, or GRIK3 to form functional channels. Homomeric associations do not produce any channel activity (By similarity). http://togogenome.org/gene/10090:Tars2 ^@ http://purl.uniprot.org/uniprot/E9Q7H6|||http://purl.uniprot.org/uniprot/Q3UQ84|||http://purl.uniprot.org/uniprot/Q922A3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain.|||Homodimer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Acox1 ^@ http://purl.uniprot.org/uniprot/Q9R0H0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the acyl-CoA oxidase family.|||Highest levels of isoform 1 are found in liver and kidney while highest levels of isoform 2 are found in white adipose tissue. Isoform 1 is expressed at higher levels than isoform 2 in liver and kidney while isoform 2 is expressed at higher levels in brain, heart, lung, muscle, white adipose tissue and testis.|||Homodimer (By similarity). Interacts with LONP2 (By similarity).|||Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids. Catalyzes the desaturation of fatty acyl-CoAs such as palmitoyl-CoA (hexadecanoyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs) such as (2E)-hexadecenoyl-CoA, and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)).|||Is active against a much broader range of substrates and shows activity towards long-chain acyl-CoAs.|||Peroxisome|||Severe microvesicular hepatic steatosis, sustained activation of Ppara, spontaneous massive peroxisome proliferation and eventual development of hepatocellular carcinomas (PubMed:20195242). Null mice have strikingly increased levels of both n-3 and n-6 very long chain polyunsaturated fatty acids (over twenty-four (24) carbons long) (PubMed:11855929).|||Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro. http://togogenome.org/gene/10090:Zswim2 ^@ http://purl.uniprot.org/uniprot/Q9D9X6 ^@ Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Dimer. Interacts with UBE2D1.|||E3 ubiquitin-protein ligase involved in the regulation of Fas-, DR3- and DR4-mediated apoptosis. Functions in conjunction with the UBE2D1, UBE2D3 and UBE2E1 E2 ubiquitin-conjugating enzymes.|||Expressed only in testis.|||Polyubiquitinated. Polyubiquitination is followed by degradation via the proteasome.|||The SWIM-type zinc finger is required for ubiquitination activity. http://togogenome.org/gene/10090:Or8j3b ^@ http://purl.uniprot.org/uniprot/Q7TR75 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zbtb7a ^@ http://purl.uniprot.org/uniprot/O88939 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Death around 16.5 dpc because of severe anemia with a profound block in early B-cell development (PubMed:17495164). Conditional knockout in erythroid cells, leads to the expression of fetal globin in peripheral blood of adult mice and inefficient erythroid terminal differentiation (PubMed:26816381).|||Expressed at 9.5-10.0 dpc in limb buds, pharyngeal arches, tail bud, placenta and neural tube (PubMed:9927193). Up-regulated during adipocyte differentiation (PubMed:14701838).|||Homodimer (By similarity). Interacts with BCL6 (PubMed:9927193). Interacts with RELA; involved in the control by RELA of the accessibility of target gene promoters (PubMed:29813070). Interacts with AR (via NR LBD domain); the interaction is direct and androgen-dependent (By similarity). Interacts with NCOR1 (By similarity). Interacts with NCOR2 (By similarity). Interacts with SMAD4; the interaction is direct and stimulated by TGFB1 (By similarity). Interacts with HDAC1 (By similarity). Interacts with SP1; ZBTB7A prevents the binding to GC-rich motifs in promoters and represses the transcriptional activity of SP1 (By similarity). Interacts with the DNA-dependent protein kinase complex/DNA-PKc (PubMed:26446488). Interacts with KHDRBS1; negatively regulates KHDRBS1 splicing activity (By similarity).|||Nucleus|||Sumoylated. Undergoes sumoylation with SUMO1 that may regulate its transcriptional activity.|||The BTB domain mediates the interaction with the androgen receptor/AR and HDAC1. Also mediates the interaction with SP1.|||Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation (PubMed:15337766, PubMed:15662416, PubMed:17495164, PubMed:26816381, PubMed:29813070). Directly and specifically binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses transcription both by regulating the organization of chromatin and through the direct recruitment of transcription factors to gene regulatory regions (PubMed:15337766, PubMed:15662416, PubMed:26816381, PubMed:29813070). Negatively regulates SMAD4 transcriptional activity in the TGF-beta signaling pathway through these two mechanisms (By similarity). That is, recruits the chromatin regulator HDAC1 to the SMAD4-DNA complex and in parallel prevents the recruitment of the transcriptional activators CREBBP and EP300 (By similarity). Collaborates with transcription factors like RELA to modify the accessibility of gene transcription regulatory regions to secondary transcription factors (PubMed:29813070). Also directly interacts with transcription factors like SP1 to prevent their binding to DNA (By similarity). Functions as an androgen receptor/AR transcriptional corepressor by recruiting NCOR1 and NCOR2 to the androgen response elements/ARE on target genes (By similarity). Thereby, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (By similarity). Involved in the switch between fetal and adult globin expression during erythroid cells maturation (PubMed:26816381). Through its interaction with the NuRD complex regulates chromatin at the fetal globin genes to repress their transcription (PubMed:26816381). Specifically represses the transcription of the tumor suppressor ARF isoform from the CDKN2A gene (PubMed:15662416). Efficiently abrogates E2F1-dependent CDKN2A transactivation (PubMed:15662416). Regulates chondrogenesis through the transcriptional repression of specific genes via a mechanism that also requires histone deacetylation (PubMed:15337766). Regulates cell proliferation through the transcriptional regulation of genes involved in glycolysis (By similarity). Involved in adipogenesis through the regulation of genes involved in adipocyte differentiation (By similarity). Plays a key role in the differentiation of lymphoid progenitors into B and T lineages (PubMed:17495164). Promotes differentiation towards the B lineage by inhibiting the T-cell instructive Notch signaling pathway through the specific transcriptional repression of Notch downstream target genes (PubMed:17495164). Also regulates osteoclast differentiation (By similarity). May also play a role, independently of its transcriptional activity, in double-strand break repair via classical non-homologous end joining/cNHEJ (PubMed:26446488). Recruited to double-strand break sites on damage DNA, interacts with the DNA-dependent protein kinase complex and directly regulates its stability and activity in DNA repair (PubMed:26446488). May also modulate the splicing activity of KHDRBS1 toward BCL2L1 in a mechanism which is histone deacetylase-dependent and thereby negatively regulates the pro-apoptotic effect of KHDRBS1 (By similarity).|||Widely expressed (PubMed:9927193). In normal thymus, expressed in medullary epithelial cells and Hassle's corpuscles (at protein level) (PubMed:15662416). In the spleen, mainly expressed in the white pulp germinal centers (at protein level) (PubMed:15662416). Up-regulated in thymic lymphomas (PubMed:15662416). http://togogenome.org/gene/10090:Cdh12 ^@ http://purl.uniprot.org/uniprot/Q5RJH3 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types (By similarity).|||Cell membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Tmem161a ^@ http://purl.uniprot.org/uniprot/Q8VCA6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM161 family.|||May play a role in protection against oxidative stress. Overexpression leads to reduced levels of oxidant-induced DNA damage and apoptosis (By similarity).|||Membrane http://togogenome.org/gene/10090:Chrm3 ^@ http://purl.uniprot.org/uniprot/Q542R4|||http://purl.uniprot.org/uniprot/Q9ERZ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily.|||Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM3 sub-subfamily.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in cerebral cortex, submandibular gland, hypothalamus, pancreas, liver, and ileum.|||Homodimer; the dimers can form tetramers (By similarity). Interacts with NALCN (PubMed:19575010). Interacts with TMEM147 (By similarity).|||Lateral cell membrane|||Membrane|||Postsynaptic cell membrane|||The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. http://togogenome.org/gene/10090:Tbc1d15 ^@ http://purl.uniprot.org/uniprot/Q9CXF4 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a GTPase activating protein for RAB7A. Does not act on RAB4, RAB5 or RAB6.|||Cytoplasm|||Interacts with non-phosphorylated form of RAB8A; phosphorylation of RAB8A at 'Thr-72' disrupts this interaction (By similarity). Interacts with ARMC12 (By similarity).|||PubMed:16055087 showns that TBC1D15 can also functions as GTPase activating for RAB11 at a lower extent than for RAB7A, however this function is not confirmed by PubMed:20363736.|||Ubiquitous, with highest expression in heart, liver and testis and lower expression in brain, spleen, lung, kidney and skeletal muscle. http://togogenome.org/gene/10090:Zhx2 ^@ http://purl.uniprot.org/uniprot/Q8C0C0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor (PubMed:19515908). Represses the promoter activity of the CDC25C gene stimulated by NFYA (By similarity). May play a role in retinal development where it regulates the composition of bipolar cell populations, by promoting differentiation of bipolar OFF-type cells (PubMed:30146259). In the brain, may promote maintenance and suppress differentiation of neural progenitor cells in the developing cortex (PubMed:19515908).|||Belongs to the ZHX family.|||Expressed in retina where it localizes to Muller glial cells of the inner nuclear layer (at protein level) (PubMed:30146259). Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis (PubMed:14659886).|||Homodimer (via homeobox domain 1) (By similarity). Heterodimer with ZHX1 (via homeobox domain 1) (By similarity). Heterodimer with ZHX3 (via homeobox domain 1) (By similarity). Heterodimerization with ZHX1 is not necessary for repressor activity (By similarity). Interacts (via homeobox domain) with NFYA (via N-terminus) (By similarity). Interacts with EFNB1 intracellular domain peptide; the interaction enhances ZHX2 transcriptional repression activity (PubMed:19515908).|||Nucleus|||Strongly expressed in retina from embryonic stages 14.5 dpc to 17.5 dpc, where it is widely detected in retinal progenitor cells (at protein level) (PubMed:30146259). Expression then gradually declines and stabilizes at a low level by postnatal day 10 (P10) (at protein level) (PubMed:30146259). At P0, expression refines to the inner half of the neuroblastic layer (at protein level) (PubMed:30146259). Expression further refines to the retinal inner nuclear layer from stage P3 onwards (at protein level) (PubMed:30146259). Detected in bipolar OFF-type cells at stage P7 (at protein level) (PubMed:30146259). By stage P10, has only weak expression in bipolar OFF-type cells but strong expression in Muller glial cells (at protein level) (PubMed:30146259). Detected in brain at embryonic stages 12.5 dpc to 15.5 dpc, specifically in the ventricular zone and subventricular zone of the cortex (at protein level) (PubMed:19515908). Probably localizes to neural progenitor cells in the developing cortex (at protein level) (PubMed:19515908). http://togogenome.org/gene/10090:Tpst2 ^@ http://purl.uniprot.org/uniprot/O88856|||http://purl.uniprot.org/uniprot/Q3TQN1 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein sulfotransferase family.|||Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.|||Golgi apparatus membrane|||Homodimer. Can also form heterodimers with TPST1.|||N-glycosylated.|||Substrate peptides must be flexible in order to adopt an L-shaped conformation in the deep binding cleft.|||Widely expressed. http://togogenome.org/gene/10090:Fat2 ^@ http://purl.uniprot.org/uniprot/Q5F226 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell junction|||Cell membrane|||Homodimer.|||Involved in the regulation of cell migration (By similarity). May be involved in mediating the organization of the parallel fibers of granule cells during cerebellar development (By similarity).|||trans-Golgi network http://togogenome.org/gene/10090:H3c6 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Alg11 ^@ http://purl.uniprot.org/uniprot/A0A077K846|||http://purl.uniprot.org/uniprot/Q3TZM9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.|||Endoplasmic reticulum membrane|||Mannosyltransferase involved in the last steps of the synthesis of Man5GlcNAc(2)-PP-dolichol core oligosaccharide on the cytoplasmic face of the endoplasmic reticulum. Catalyzes the addition of the 4th and 5th mannose residues to the dolichol-linked oligosaccharide chain (By similarity).|||Required for N-linked oligosaccharide assembly. http://togogenome.org/gene/10090:Acta2 ^@ http://purl.uniprot.org/uniprot/P62737 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.|||Belongs to the actin family.|||Expressed in the liver (at protein level).|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Induced by S.japonicum egg-mediated liver fibrosis at the site of egg granulomas; expression peakes at 12 weeks post infection with expression decreasing thereafter.|||Methylated at His-75 by SETD3.|||Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration (By similarity).|||N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.|||Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.|||cytoskeleton http://togogenome.org/gene/10090:Grpr ^@ http://purl.uniprot.org/uniprot/P21729 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in pancreas and brain (PubMed:1671171, PubMed:9345264). Detected in suprachaismatic nucleus neurons (PubMed:28280205). Detected in neurons in the dorsal horn of the spinal cord (PubMed:17653196). Detected in inhibitory GABAergic interneurons in the lateral nucleus of the amygdala (PubMed:12526815). Detected in approximately 160 neurons of the pre-Botzinger complex (PubMed:26855425). Within the pre-Botzinger complex, there is some overlap with neurons expressing Nmbr with some cells expressing only Grpr or Nmbr while some cells express both (PubMed:26855425). Detected in cells throughout the cortex where it is coexpressed in most of these cells with vasointestinal peptide (VIP) (PubMed:34610277).|||Mice are born at the expected Mendelian rate, are viable and fertile (PubMed:9345264). They do not decrease their food intake in response to gastrin-releasing peptide (PubMed:12176666). Mice consume more food per meal, but the overall food intake per day remains unchanged (PubMed:12176666). Still, they display increased body weight relative to wild-type (PubMed:12176666). Contrary to wild-type mice, their body temperature remains nearly constant when exposed to cold (4 degrees Celsius) after intracerebroventricular injection of gastrin-releasing peptide (PubMed:9345264). Mutant mice show increased locomotor activity and increased social interactions (PubMed:9345264). They do not show any change in the perception of painful stimuli, but show reduced scratching in response to pruritogenic treatments (PubMed:17653196). Contrary to wild-type, mutant mice do not display imitative scratching after observing spontaneous scratching behavior in another mouse (PubMed:28280205). In one study, mutant mice display normal performance in a water maze, but show decreased inhibition of principal neurons by the interneurons, enhanced long-term potentiation (LTP), and greater and more persistent long-term fear memory (PubMed:12526815). Another study showed that mutants display reduced long-term fear memory (PubMed:34610277). Reduced basal sigh rate (PubMed:26855425). Conditional knockout in the auditory cortex results in diminished auditory fear memories with no significant effect on auditory discrimination (PubMed:34610277).|||Receptor for gastrin-releasing peptide (GRP) (PubMed:1671171, PubMed:1707129, PubMed:9345264, PubMed:12526815, PubMed:26658875). Signals via association with G proteins that activate a phosphatidylinositol-calcium second messenger system, resulting in Akt phosphorylation (PubMed:26658875). Contributes to the regulation of food intake (PubMed:12176666). Contributes to the perception of prurient stimuli and transmission of itch signals in the spinal cord that promote scratching behavior, but does not play a role in the perception of pain (PubMed:28280205, PubMed:17653196, PubMed:26658875). Contributes primarily to nonhistaminergic itch sensation (PubMed:28280205). In one study, shown to act in the amygdala as part of an inhibitory network which inhibits memory specifically related to learned fear (PubMed:12526815). In another study, shown to contribute to disinhibition of glutamatergic cells in the auditory cortex via signaling on vasoactive intestinal peptide-expressing cells which leads to enhanced auditory fear memories (PubMed:34610277). Contributes to the induction of sighing through signaling in the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity (PubMed:26855425). http://togogenome.org/gene/10090:Marchf4 ^@ http://purl.uniprot.org/uniprot/Q80TE3 ^@ Domain|||Function|||Subcellular Location Annotation ^@ E3 ubiquitin-protein ligase that may mediate ubiquitination of MHC-I and CD4, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.|||Golgi apparatus membrane|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Enah ^@ http://purl.uniprot.org/uniprot/A0A0A6YW06|||http://purl.uniprot.org/uniprot/E9QKQ9|||http://purl.uniprot.org/uniprot/E9QLZ9|||http://purl.uniprot.org/uniprot/Q03173 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc, particularly enriched in the neuroepithelium, the forebrain and the somites. Highly expressed in the edges of the neural folds. By 10.5 dpc, detected in the brain, dorsal root ganglia (DRG), somites and limb buds. Highly expressed in the branchial and pharyngeal arches, neural crest-derived structures that give rise to portions of the face and neck. At 11 dpc, isoform 2, isoform 3 and isoform 5 are expressed in embryonic brain (at protein level). Expression of isoform 3 decreases steadily and becomes almost undetectable by 16 dpc, while expression of isoform 5 begins to increase from 13 dpc and peaks between 16 and 18 dpc (at protein level).|||Belongs to the Ena/VASP family.|||Cytoplasm|||Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation.|||Expressed in heart and testis, lower levels in lung, skeletal muscle, kidney, pancreas and brain. Isoform 5 is expressed exclusively in the brain. Isoform 2 is expressed predominantly in brain, testis, ovary and fat. In the brain, isoforms 2 and 5 are expressed at highest levels in the hippocampus, cortex and midbrain, and at lowest levels in the striatum and cerebellum. Isoform 6 is expressed in brain and spleen.|||Homotetramer (By similarity). Interacts with APBB1IP, APBB1, PFN1 and ROBO4. Isoforms, containing the polyproline-rich regions with PPLP motifs, bind the WW domain of APBB1IP. Isoforms, containing the PPSY motif, bind, in vitro, to the WW2 and WW3 domains of NEDD4 and to the WW1 domain of YAP1. Binds the SH3 domain of BAIAP2-alpha but only after the autoinhibitory region of BAIAP2-alpha has been blocked by interaction with CDC42. Interacts, via the EVH1/WH1 domain, with the Pro-rich domains from VCL, ZYX and Listeria monocytogenes actA and with TES (via LIM domain). The TES LIM domain and the Pro-rich domains from VCL or ZYX compete for the same binding site. Interaction with ZYX is important for targeting ENAH to focal adhesions and enhances production of actin-rich structures at the apical surface of cells. Binds GPHN. Heterotrimer with TES and ACTL7A (By similarity). Interacts with FAT1 (via EVH1 domains) (PubMed:15148305). Interacts, through the Pro-rich region, with the C-terminal SH3 domain of DNMPB (PubMed:14506234) (Probable). Interacts with PRPF40A (PubMed:9171351).|||Mutant animals are viable and recovered in the appropriate Mendelian ratios. they are smaller than their littermates until adulthood and exhibit abnormal cage behavior, including reduced activity.|||NTN1-induced PKA phosphorylation on Ser-255 directly parallels the formation of filopodial protrusions.|||Phosphorylated during neural development.|||Required to transform actin polymerization into active movement for the propulsive force of Listeria monocytogenes.|||Synapse|||The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.|||cytoskeleton|||filopodium|||focal adhesion|||lamellipodium http://togogenome.org/gene/10090:Cyyr1 ^@ http://purl.uniprot.org/uniprot/Q8VIH7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CYYR1 family.|||Membrane http://togogenome.org/gene/10090:Smchd1 ^@ http://purl.uniprot.org/uniprot/Q6P5D8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical member of the structural maintenance of chromosomes (SMC) protein family (PubMed:26733688, PubMed:27059856). Like other members of the SMC family, has ATPase activity, which is probably necessary for its engagement with chromatin, and a SMC hinge domain (PubMed:26733688, PubMed:27059856). However, the SMC hinge domain adopts an unconventional homodimeric arrangement augmented by an intermolecular coiled coil formed between the two monomers. This suggests that protein may assemble as a head-to-head parallel dimer without adopting a hairpin shape at the hinge domain, unlike the dimeric arrangement conventionally found in other members of the SMC protein family (PubMed:26733688). The SMC hinge domain binds DNA and RNA (PubMed:26091879).|||Belongs to the SMC family. Highly divergent.|||Chromosome|||Defects in Smchd1 are the cause of the MommeD1 (modifier of murine metastable epialleles) phenotype, a semi-dominant suppressor of variegation (PubMed:18425126, PubMed:21553025). Mice display female-specific mid-gestation lethality and hypomethylation of the X-linked gene Hprt1, due to defects in X inactivation (PubMed:18425126, PubMed:21553025, PubMed:23754746). Mice do not show defects on telomeres length (PubMed:18425126, PubMed:21553025). Male mice are less affected, with some surviving to become fertile adults on the FVB/n genetic background (PubMed:18425126). On other genetic backgrounds, all males lacking die perinatally (PubMed:18425126). A subset of clustered autosomal loci display hypomethylation and derepression (PubMed:23754746, PubMed:23819640, PubMed:28587678).|||During embryogenesis, specifically expressed in immature olfactory sensory neurons.|||Expressed in the nasal placodes and optic vesicles at day 9.5 dpc and in the nasal epithelium at 12.5 dpc (PubMed:28067911). Expressed in the nasal cavity in 14.5 dpc animals (PubMed:28067911).|||Expression is repressed by CDX2.|||Homodimer; homodimerizes via its SMC hinge domain (PubMed:26391951, PubMed:26733688, PubMed:27059856). Interacts with LRIF1 (PubMed:26391951).|||Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture (PubMed:26091879, PubMed:29887375). Promotes heterochromatin formation in both autosomes and chromosome X, probably by mediating the merge of chromatin compartments (PubMed:23754746, PubMed:23819640, PubMed:26391951, PubMed:28587678, PubMed:29887375). Plays a key role in chromosome X inactivation in females by promoting the spreading of heterochromatin (PubMed:18425126, PubMed:22841499, PubMed:26391951, PubMed:29887375). Recruited to inactivated chromosome X by Xist RNA and acts by mediating the merge of chromatin compartments: promotes random chromatin interactions that span the boundaries of existing structures, leading to create a compartment-less architecture typical of inactivated chromosome X (PubMed:29887375). Required to facilitate Xist RNA spreading (PubMed:29887375). Also required for silencing of a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus (PubMed:23754746, PubMed:23819640, PubMed:28587678). Has ATPase activity; may participate in structural manipulation of chromatin in an ATP-dependent manner as part of its role in gene expression regulation (PubMed:26391951, PubMed:27059856). Also plays a role in DNA repair: localizes to sites of DNA double-strand breaks in response to DNA damage to promote the repair of DNA double-strand breaks (By similarity). Acts by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination (HR) repair (By similarity). Required during preimplantation development, probably acts by regulating chromatin architecture (PubMed:29900695).|||Sumoylated with SUMO1. http://togogenome.org/gene/10090:Pierce2 ^@ http://purl.uniprot.org/uniprot/V9GXK1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIERCE2 family.|||Interacts with CFAP53, ODAD1 and ODAD3; the interactions link the outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.|||Microtubule inner protein involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||Mutants born at the expected frequency (PubMed:34715025). At 8 dpc, they have a reduced beat frequency of nodal cilia (PubMed:34715025). The motility of tracheal cilia in adult mice is also affected (PubMed:34715025). 25% of tracheal cilia axonemes have missing dynein arms (PubMed:34715025). Double PIERCE1 and PIERCE2 mutants show high levels of embryonic and pre-weaning lethality. The few mice that survive birth display hydrocephalus and laterality abnormalities, dying by 20 days of age (PubMed:34715025).|||cilium axoneme http://togogenome.org/gene/10090:Sdhaf4 ^@ http://purl.uniprot.org/uniprot/Q8BTE0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SDHAF4 family.|||Interacts with Sdha in its FAD-bound form.|||Mitochondrion matrix|||Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol (PubMed:24954416). Binds to the flavoprotein subunit Sdha in its FAD-bound form, blocking the generation of excess reactive oxygen species (ROS) and facilitating its assembly with the iron-sulfur protein subunit Sdhb into the SDH catalytic dimer (By similarity). http://togogenome.org/gene/10090:Grn ^@ http://purl.uniprot.org/uniprot/P28798|||http://purl.uniprot.org/uniprot/Q3U9N4|||http://purl.uniprot.org/uniprot/Q544Y8|||http://purl.uniprot.org/uniprot/Q9D2V3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the granulin family.|||Cleaved by ELANE; proteolysis is blocked by SLPI and is concentration- and time-dependent and induces CXCL8/IL-8 production; granulin-3 and granulin-4 are resistant to ELANE (By similarity). Cleaved by CTSL in lysosome thus regulating the maturation and turnover of progranulin within the lysosome (PubMed:28835281).|||Highly expressed at the wound site and diminishes away from the wound. Not expressed in fibroblasts and endothelial cells in intact skin (PubMed:12524533). In adult brain, expressed primarily in neurons and in resting and reactive microglia (PubMed:23041626). Expressed in both neurons and microglia. Highly expressed in activated microglia in response to injury (PubMed:28541286). Expressed in macrophage (PubMed:27789271).|||Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8.|||Injury-stimulated induction in the fibroblasts and endothelial cells and by inflammatory cells entering the wound (PubMed:12524533). Injury-stimulated induction in neurons (PubMed:28453791). Strongly induced in activated microglial cells that surround motor neurons after peripheral axonal injury, but not by astrocytes (PubMed:21092856). Up-regulated in response to a cortical injury. Up-regulated in activated glia during normal aging (PubMed:28541286). Induced in response to inflammation (PubMed:27789271).|||Lysosome|||N-glycosylated.|||Progranulin is secreted as a homodimer (By similarity). Interacts with SLPI; interaction protects progranulin from proteolysis (PubMed:12526812). Interacts (via region corresponding to granulin-7 peptide) with CTSD; stabilizes CTSD and increases its proteolytic activity. Interacts (via region corresponding to granulin-7 peptide) with SORT1; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (By similarity). Interacts with PSAP; facilitates lysosomal delivery of progranulin from the extracellular space and the biosynthetic pathway (PubMed:26370502). Forms a complex with PSAP and M6PR; PSAP bridges the binding between progranulin and M6PR. Forms a complex with PSAP and SORT1; progranulin bridges the interaction between PSAP and SORT1; facilitates lysosomal targeting of PSAP via SORT1; interaction enhances PSAP uptake in primary cortical neurons (By similarity). Interacts (via regions corresponding to granulin-2 and granulin-7 peptides) with GBA1; this interaction prevents aggregation of GBA1-SCARB2 complex via interaction with HSPA1A upon stress (PubMed:27789271). Interacts (via region corresponding to granulin-7 peptide) with HSPA1A; mediates recruitment of HSPA1A to GBA1 and prevents GBA1 aggregation in response to stress (By similarity).|||Secreted|||Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:28073925, PubMed:8496151, PubMed:28541286, PubMed:28453791, PubMed:20026663, PubMed:23041626, PubMed:27789271, PubMed:12524533). Regulates protein trafficking to lysosomes and, also the activity of lysosomal enzymes (PubMed:28453791, PubMed:28541286, PubMed:27789271). Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB (PubMed:28073925). In addition, functions as wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures (PubMed:12524533). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases (PubMed:8496151). Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity (PubMed:23041626, PubMed:20026663).|||Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity.|||Young-adult knockout mice are healthy and fertile, grow normally and show no abnormalities in hematogram or serum chemistries. However they show increased inflammation levels, impaired host defense, and neuropathology (PubMed:20026663). Knockout animals displays neuronal outgrowth deficit. They exhibit increased neuron death and microglial activation upon central nervous system injury (CNS). Conditional knockout mice exhibit a reduction in dopaminergic neurons and increased microgliosis after CNS injury (PubMed:23041626). In neurons, conditional knockout mice show a significant delay in axonal regrowth and functional recovery after crush (PubMed:28453791). At 2 months of age, knockout animals exhibit up-regulation of the expression level of many lysosomal proteins, including that of cathepsin B/CTSB, cathepsin L/CTSL, dipeptidyl peptidase 2/DPP7 and LAMP1. At 4 months of age, knockout mice show increased locomotor activity in the open-field behavior test as compared to wild-type animals. They are also less anxious and disinhibited than wild-type littermates. Retinal degeneration can be observed as early as 5 months of age (PubMed:20026663, PubMed:23041626, PubMed:28453791). Mice deficient in both PGRN and TMEM106B are born at normal Mendelian frequency and do not show any obvious growth defects or body weight changes. At around 3.5 months of age, the animals develop severe ataxia, hindlimb weakness, reduced motor activity, altered clasping behavior and eventually premature death. Neuronal loss and severe microglia and astrocyte activation are observed in the spinal cord, retina, and brain (PubMed:32761777, PubMed:32852886, PubMed:32929860). Myelin degeneration occurs in the spinal cord (PubMed:32761777). Drastic autophagy and lysosomal abnormalities, as well as other pathological changes related to frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis are observed (PubMed:32761777, PubMed:32852886, PubMed:32929860). Most studies consistently show that loss of TMEM106B exacerbates lysosome abnormalities found in GRN-single knockout animals, likely contributing to neuronal dysfunction and neuronal death (PubMed:32761777, PubMed:32852886, PubMed:32929860). However, one study reports that the expression levels of most lysosomal proteins are normalized in double knockout mice and comparable to those of wild-type animals and some behavioral phenotypes observed in GRN-single knockout mice, such as locomotor hyperactivity, disinhibition and retinal degeneration, are rescued in double knockout (PubMed:28728022). http://togogenome.org/gene/10090:Rtn4 ^@ http://purl.uniprot.org/uniprot/Q99P72 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to RTN4R (By similarity). Interacts with ATL1 (By similarity). Interacts with TMEM170A (By similarity). Interacts with RTN4IP1 (PubMed:12067236).|||Cell junction|||Cell membrane|||Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system (PubMed:20573699). Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (By similarity). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (PubMed:20573699). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (PubMed:23625008).|||Endoplasmic reticulum membrane|||Expressed at very low levels in neurons.|||Expressed in B-cells, bone marrow dendritic cells and macrophages (at protein level).|||Expressed in cardiomyocytes (at protein level) (PubMed:32075961). Expressed in splenocytes, T-cells, B-cells, bone marrow derived dendritic cells and macrophages (at protein level) (PubMed:19805174, PubMed:25917084). Expressed in neurons (PubMed:23625008, PubMed:27786289). Highly expressed in endothelial cells and vascular smooth muscle cells, including blood vessels and mesenteric arteries (PubMed:15034570, PubMed:26301690). Expressed in bronchial and alveolar epithelial cells as well as vascular endothelial cells of lungs (PubMed:26174362).|||Expressed in cardiomyocytes (at protein level) (PubMed:32075961). Highly expressed in brain but not deteceted in aorta, femoral and carotid arteries (PubMed:15034570). Main isoform expressed in neurons (PubMed:23625008, PubMed:27786289).|||Expressed in cardiomyocytes.|||Expressed in radial glial cells, migrating postmitotic as well as postmigratory neurons of the embryonic cortex (PubMed:20093372). Expression is down-regulated in the ganglion cell layer and in the plexiform layer of the retina at P8 (PubMed:20093372). Isoform B: expression increases in regenirating liver (PubMed:23299899).|||Homodimer (By similarity). Interacts with BAD/Bcl-xl and BCL2. Interact with RTN3 (By similarity). Interacts with NGBR (By similarity). Interacts with SPTLC1 (PubMed:26301690). Interacts with GRAMD4 (PubMed:25917084). Interacts with CDH5 (By similarity). Interacts with BACE1 and BACE2 (By similarity). Interacts with REEP5 (PubMed:32075961). Interacts with RETREG3 (By similarity).|||Interacts in trans with CNTNAP1 (By similarity). Interacts with REEP5 (PubMed:32075961).|||Interacts with BACE1 and BACE2 (By similarity). Interacts with TMEM33 (By similarity).|||Isoform A mutant embryos show defects in the development of fore- and hindlimb innervation. Increased fasciculation and decreased branching of nerves innervating fore- and hindlimbs seen. Disturbances of the radial migration pattern of neuronal precursor cells seen in embryonic cortex (PubMed:20093372, PubMed:20573699). Isoform A mutants show increased density of blood vessels in postnatal brain, which is lost in adult brain (PubMed:23625008). Knockout mice for isoforms A and B are markedly hypotensive compared to control mice, with no significant increase of heart rate. They have mesenteric arteries thinner than controls (PubMed:26301690). Upon vascular injury mutants show markedly enhanced neointima formation and, in some cases, complete occlusion of the femoral artery (PubMed:15034570). Mutants for isoforms A and B show a marked reduction in neutrophil and monocyte recruitment to sites of inflammation (PubMed:21183689). Mutants for isoforms A and B are insensitive to stimulation with TLR9, TLR3 and TLR7 ligands (PubMed:25917084). Mutant mice for isoform C display improved cardiac function, smaller infarct area and less apoptotic cells after myocardial infarction (PubMed:27763637). Knockout mice show impaired responses to tissue injury (PubMed:19805174).|||Isoform C: expression is induced by hypoxic treatments or myocardial infarction (PubMed:27763637). Isoform C: is negatively regulated by the microRNA miR-182 (PubMed:27763637). Isoform B: expression is down-regulated by LPS in alveolar epithelium (PubMed:26174362). Isoform B: induced during tissue ischemia (PubMed:19805174). Isoform B2: induced during tissue ischemia (PubMed:19805174).|||Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells (PubMed:15034570). Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P) (PubMed:26301690). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair (PubMed:19805174). Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation (PubMed:21183689). Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes (PubMed:25917084). Also involved in immune response to LPS (PubMed:26174362). Plays a role in liver regeneration through the modulation of hepatocytes proliferation (PubMed:23299899). Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (By similarity).|||N-terminal part, called Am-Nogo-B(1-200), is the functional domain for RTN4B-mediated signaling in endothelial and vascular smooth muscle cells.|||Regulates cardiomyocyte apoptosis upon hypoxic conditions (PubMed:27763637). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (By similarity).|||Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules. They regulate membrane morphogenesis in the ER by promoting tubular ER production. They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins. However each isoform have specific functions mainly depending on their tissue expression specificities.|||Three regions, residues 59-172, 544-725 and the loop 66 amino acids, between the two transmembrane domains, known as Nogo-66 loop, appear to be responsible for the inhibitory effect on neurite outgrowth and the spreading of neurons. This Nogo-66 loop, mediates also the binding of RTN4 to its receptor (By similarity). http://togogenome.org/gene/10090:Capn1 ^@ http://purl.uniprot.org/uniprot/O35350|||http://purl.uniprot.org/uniprot/Q3TB79|||http://purl.uniprot.org/uniprot/Q3TI07|||http://purl.uniprot.org/uniprot/Q3UF24 ^@ Activity Regulation|||Caution|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by micromolar concentrations of calcium and inhibited by calpastatin.|||Belongs to the peptidase C2 family.|||Binds 4 Ca(2+) ions.|||Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-388' and 'His-410'. Cleaves and activates caspase-7 (CASP7).|||Cell membrane|||Cytoplasm|||Forms a heterodimer with a small (regulatory) subunit CAPNS1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Undergoes calcium-induced successive autoproteolytic cleavages that generate a membrane-bound 78 kDa active form and an intracellular 75 kDa active form. Calpastatin reduces with high efficiency the transition from 78 kDa to 75 kDa calpain forms (By similarity). http://togogenome.org/gene/10090:Dennd4b ^@ http://purl.uniprot.org/uniprot/Q3U1Y4 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Golgi apparatus|||Guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity).|||Wrong gene model based on unspliced pre-RNA. http://togogenome.org/gene/10090:Tecrl ^@ http://purl.uniprot.org/uniprot/Q8BFZ1|||http://purl.uniprot.org/uniprot/Q8BWI9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At embryonic day 8.5 dpc, expressed in the developing heart with the strongest expression occurring in the inflow tract, especially in the left horn. At 9.5 dpc, expression is still detectable in the atria and ventricles, albeit at lower levels whereas strong expression remains in the inflow tract. From 10 dpc onwards, it is also expressed at low levels in somites, particularly in the myotome region, that gives rise to skeletal muscle. At 10.5 dpc, cardiac expression is no longer restricted to the inflow tract. At 14.5 dpc, it is expressed in the entire myocardium.|||Belongs to the steroid 5-alpha reductase family.|||Endoplasmic reticulum|||Expression is highest in the heart with very low to almost undetectable levels in brain, skeletal muscle, stomach, pancreas, liver, kidney, small intestine, and uterus.|||Membrane http://togogenome.org/gene/10090:Fam180a ^@ http://purl.uniprot.org/uniprot/Q8BR21 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM180 family.|||Secreted http://togogenome.org/gene/10090:Ralgapa2 ^@ http://purl.uniprot.org/uniprot/A3KGS3 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in testis, pancreas, lung, thymus, brown fat, and white fat.|||Catalytic subunit of the heterodimeric RalGAP2 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB.|||Component of the heterodimeric RalGAP2 complex with RALGAPB. Heterodimerization is required for activity (By similarity).|||Cytoplasm|||Probable cloning artifact leading to erroneous C-terminus. http://togogenome.org/gene/10090:Rpl7a ^@ http://purl.uniprot.org/uniprot/P12970|||http://purl.uniprot.org/uniprot/Q58ET1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL8 family.|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with CRY1 (PubMed:19129230). Interacts with DICER1, AGO2, TARBP2, MOV10 and EIF6; they form a large RNA-induced silencing complex (RISC) (By similarity).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the ribosome.|||Cytoplasm http://togogenome.org/gene/10090:Oxgr1 ^@ http://purl.uniprot.org/uniprot/Q6IYF8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Predominantly expressed in the kidney with limited expression in the testis and the smooth muscle.|||Receptor for alpha-ketoglutarate. Seems to act exclusively through a G(q)-mediated pathway. http://togogenome.org/gene/10090:Senp7 ^@ http://purl.uniprot.org/uniprot/E9Q1L5|||http://purl.uniprot.org/uniprot/Q8BUH8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C48 family.|||Cytoplasm|||Protease that acts as a positive regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS (PubMed:28095500). Desumoylation of CGAS promotes DNA-binding activity of CGAS, subsequent oligomerization and activation (PubMed:28095500). Deconjugates SUMO2 and SUMO3 from targeted proteins, but not SUMO1 (By similarity). Catalyzes the deconjugation of poly-SUMO2 and poly-SUMO3 chains (By similarity). Has very low efficiency in processing full-length SUMO proteins to their mature forms (By similarity). http://togogenome.org/gene/10090:Zc3h3 ^@ http://purl.uniprot.org/uniprot/Q8CHP0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with SMAD1, SMAD3, SMAD4, CPSF2 and CPSF3.|||Nucleus|||Required for the export of polyadenylated mRNAs from the nucleus (By similarity). Enhances ACVR1B-induced SMAD-dependent transcription. Binds to single-stranded DNA but not to double-stranded DNA in vitro. Involved in RNA cleavage (PubMed:16115198). http://togogenome.org/gene/10090:Pou2af3 ^@ http://purl.uniprot.org/uniprot/F8VPY8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU2AF family.|||Cytoplasm|||Expressed in tuft cells.|||In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif (5'-ATGAAAT-3').|||Interacts with POU2F3 in a DNA-dependent manner; this interaction increases POU2F3 transactivation activity.|||Nucleus|||Transcriptional coactivator that specifically associates with POU2F3. This complex drives the development of tuft cells, a rare a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues. http://togogenome.org/gene/10090:Pax1 ^@ http://purl.uniprot.org/uniprot/P09084 ^@ Disease Annotation|||Function|||Subcellular Location Annotation ^@ Nucleus|||This protein is a transcriptional activator. It may play a role in the formation of segmented structures of the embryo. May play an important role in the normal development of the vertebral column.|||Undulated (un) homozygous mice exhibits vertebral malformations along the entire rostro-caudal axis. This is due to a single mutation in the paired box region. http://togogenome.org/gene/10090:Rprml ^@ http://purl.uniprot.org/uniprot/Q3URD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the reprimo family.|||Membrane http://togogenome.org/gene/10090:Glt8d2 ^@ http://purl.uniprot.org/uniprot/Q640P4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 8 family.|||Membrane http://togogenome.org/gene/10090:Or1n2 ^@ http://purl.uniprot.org/uniprot/Q8VGJ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Srrm4 ^@ http://purl.uniprot.org/uniprot/Q8BKA3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ About 85% of the mutant mice die in the first few hours after birth and few surviving animals display balance defects and exhibit persistent tremors. Mice show impaired development of the central and peripheral nervous systems in part by disrupting neurite outgrowth, cortical layering in the forebrain, and axon guidance in the corpus callosum.|||Belongs to the nSR100 family.|||Expressed in both the central and peripheral nervous system in developing mice.|||Nucleus|||Phosphorylated.|||Specifically expressed in neuronal cells (at protein level). Expressed in adult nervous system and sensory organ tissues.|||Splicing factor specifically required for neural cell differentiation. Acts in conjunction with nPTB/PTBP2 by binding directly to its regulated target transcripts and promotes neural-specific exon inclusion in many genes that function in neural cell differentiation. Required to promote the inclusion of neural-specific exon 10 in nPTB/PTBP2, leading to increased expression of neural-specific nPTB/PTBP2. Also promotes the inclusion of exon 16 in DAAM1 in neuron extracts (PubMed:19737518). Promotes alternative splicing of REST transcripts to produce REST isoform 2 (REST4) with greatly reduced repressive activity, thereby activating expression of REST targets in neural cells (PubMed:21884984). Plays an important role during embryonic development as well as in the proper functioning of the adult nervous system. Regulates alternative splicing events in genes with important neuronal functions (PubMed:25838543). http://togogenome.org/gene/10090:Scml4 ^@ http://purl.uniprot.org/uniprot/Q3UR41|||http://purl.uniprot.org/uniprot/Q80VG1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SCM family.|||Nucleus|||Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development (By similarity). http://togogenome.org/gene/10090:Or8g17 ^@ http://purl.uniprot.org/uniprot/Q60884 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Slc5a12 ^@ http://purl.uniprot.org/uniprot/B9EJ03|||http://purl.uniprot.org/uniprot/Q49B93 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an electroneutral and low-affinity sodium (Na(+))-dependent sodium-coupled solute transporter. Catalyzes the transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, nicotinate, propionate, butyrate and beta-D-hydroxybutyrate. May be responsible for the first step of reabsorption of monocarboxylates from the lumen of the proximal tubule of the kidney and the small intestine. May play also a role in monocarboxylates transport in the retina. Mediates electroneutral uptake of lactate, with a stoichiometry of 2 Na(+) for each lactate.|||Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Expressed in the cortical region of the kidney corresponding to the proximal tubule. Expressed in Mueller cells of the inner retina (at protein level). Isoform 1 is expressed in the retina, kidney, small intestine and skeletal muscle. Isoform 2 is not detected in the kidney, small intestine and skeletal muscle. In the kidney, expressed predominantly in tubular epithelial cells of the cortical region and in the convoluted portions of the proximal tubule (pars convoluta). In the small intestine, its expression is highest in the proximal part and gradually decreased towards the distal end. Expressed in the neural retina. Not detected in the caecum and colon.|||Membrane|||Up-regulated by CEBPD. http://togogenome.org/gene/10090:Nol9 ^@ http://purl.uniprot.org/uniprot/Q3TZX8 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Clp1 family. NOL9/GRC3 subfamily.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with PELP1, WDR18 and SENP3.|||Nucleus|||Polynucleotide 5'-kinase involved in rRNA processing. The kinase activity is required for the processing of the 32S precursor into 5.8S and 28S rRNAs, more specifically for the generation of the major 5.8S(S) form. In vitro, has both DNA and RNA 5'-kinase activities. Probably binds RNA (By similarity).|||nucleolus http://togogenome.org/gene/10090:Rhoj ^@ http://purl.uniprot.org/uniprot/Q9ER71 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Highly expressed in heart with moderate levels in lung and liver (PubMed:10967094). Very low levels detected in brain, spleen, skeletal muscle, kidney and testis (PubMed:10967094).|||Interacts with the CRIB domains of proteins such as Pak1 and Was/Wasp (PubMed:10967094). Interacts with GLUL (By similarity).|||Palmitoylated; regulates localization to the plasma membrane and may be mediated by GLUL.|||Plasma membrane-associated small GTPase specifically involved in angiogenesis (By similarity). Required for endothelial cell migration during vascular development via its interaction with GLUL (By similarity). Elicits the formation of F-actin-rich structures, thereby regulating endothelial cell migration (PubMed:10967094). http://togogenome.org/gene/10090:Ttc23 ^@ http://purl.uniprot.org/uniprot/Q8CHY7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associated with the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC.|||Participates positively in the ciliary Hedgehog (Hh) signaling.|||cilium http://togogenome.org/gene/10090:Capsl ^@ http://purl.uniprot.org/uniprot/Q6P8Y1 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Nalf1 ^@ http://purl.uniprot.org/uniprot/Q8CCS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxillary component of the NALCN sodium channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.|||Belongs to the NALF family.|||Cell membrane|||Component of the NALCN channel complex (PubMed:33273469). NALCN complex consists of NALCN and auxiliary subunits, UNC79, UNC80 and NACL1. These auxiliary subunits are essential for the NALCN channel function (By similarity). http://togogenome.org/gene/10090:Stk11 ^@ http://purl.uniprot.org/uniprot/Q9WTK7 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated. Deacetylation at Lys-48 enhances cytoplasmic localization and kinase activity in vitro.|||Activated by forming a complex with STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): STRADA (or STRADB)-binding promotes a conformational change of STK11/LKB1 in an active conformation, which is stabilized by CAB39/MO25alpha (or CAB39L/MO25beta) interacting with the STK11/LKB1 activation loop. Sequestration in the nucleus by NR4A1 prevents it from phosphorylating and activating cytoplasmic AMPK (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.|||Catalytic component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with p53/TP53, SMAD4, STK11IP and WDR6. Interacts with NR4A1 (By similarity). Interacts with NISCH; this interaction may increase STK11 activity (By similarity). Interacts with PTEN, leading to PTEN phosphorylation (By similarity). Interacts with SIRT1; the interaction deacetylates STK11 (By similarity). Interacts with CDKN1A.|||Cytoplasm|||Expressed in adult brain and liver and absent from tissues derived from postnatal day 7.|||Has a role in spermiogenesis.|||Membrane|||Mice die in utero 8.5 to 9.5 dpc due to severe defects in their vasculature: embryos show neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development is also severely affected; the mutant placentas exhibit defective labyrinth layer development and the fetal vessels fail to invade the placenta. Male mice specifically lacking isoform 2 are sterile (PubMed:18774945). A specifically deletion in liver results in hyperglycemia with increased gluconeogenic and lipogenic gene expression due to loss of AMPK phosphorylation and subsequent dephosphorylation of CRTC2/TORC2 (PubMed:16308421). Use of a conditional allele, leads to defects in defects in axon formation with a thinner cortical wall and larger lateral ventricles in the brain cortex (PubMed:17482548). Heterozygous mice develop multiple gastric adenomatous polyps, with polyps remarkably similar to hamartomas of PJS patients both macroscopically and histologically. Polyps in the heterozygous mice are detected at 5 months, and cause premature lethality progressively from 8 months onwards. Polyps are most frequently observed in the stomach where they typically concentrate close to the pylorus. Polyps in the small and large intestine are significantly less frequent. The histology of the polyps in the heterozygous mice is remarkably similar to PJS polyps including the relative contribution of well-differentiated epithelium, and a prominent smooth muscle component. Ptgs2/Cox2 is highly up-regulated in heterozygous mice polyps concomitantly with activation of the extracellular signal-regulated kinases Mapk1/Erk2 and Mapk3/Erk1: treatment with celecoxib Ptgs2/Cox2 inhibitor significantly reduces the total polyp burden.|||Mitochondrion|||Nucleus|||Phosphorylated by ATM at Thr-366 following ionizing radiation (IR). Phosphorylation at Ser-431 by RPS6KA1 and/or some PKA is required to inhibit cell growth. Phosphorylation at Ser-431 is also required during neuronal polarization to mediate phosphorylation of BRSK1 and BRSK2. Phosphorylation by PKC/PRKCZ at Ser-399 in isoform 2 promotes metformin (or peroxynitrite)-induced nuclear export of STK11 and activation of AMPK. UV radiation-induced phosphorylation at Thr-366 mediates CDKN1A degradation.|||Predominantly expressed in testis (at protein level).|||Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, thus promoting their activity: phosphorylates PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2, MARK3, MARK4, NUAK1, NUAK2, SIK1, SIK2, SIK3 and SNRK but not MELK. Also phosphorylates non-AMPK family proteins such as STRADA, PTEN and possibly p53/TP53. Acts as a key upstream regulator of AMPK by mediating phosphorylation and activation of AMPK catalytic subunits PRKAA1 and PRKAA2 and thereby regulates processes including: inhibition of signaling pathways that promote cell growth and proliferation when energy levels are low, glucose homeostasis in liver, activation of autophagy when cells undergo nutrient deprivation, and B-cell differentiation in the germinal center in response to DNA damage. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton. Required for cortical neuron polarization by mediating phosphorylation and activation of BRSK1 and BRSK2, leading to axon initiation and specification. Involved in DNA damage response: interacts with p53/TP53 and recruited to the CDKN1A/WAF1 promoter to participate in transcription activation. Able to phosphorylate p53/TP53; the relevance of such result in vivo is however unclear and phosphorylation may be indirect and mediated by downstream STK11/LKB1 kinase NUAK1. Also acts as a mediator of p53/TP53-dependent apoptosis via interaction with p53/TP53: translocates to the mitochondrion during apoptosis and regulates p53/TP53-dependent apoptosis pathways. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with NUAK1, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316).|||Ubiquitously expressed 7-11 dpc. Present in nucleated embryonic blood cells from 9 dpc. Restricted to gastrointestinal tract, testis and lung from days 15-19 dpc.|||Widely expressed. http://togogenome.org/gene/10090:Psd4 ^@ http://purl.uniprot.org/uniprot/Q8BLR5 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 4,5-bisphosphate (By similarity).|||ruffle membrane http://togogenome.org/gene/10090:Rnase2b ^@ http://purl.uniprot.org/uniprot/O35292|||http://purl.uniprot.org/uniprot/W0UVC5 ^@ Function|||Similarity ^@ Belongs to the pancreatic ribonuclease family.|||This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Possesses a wide variety of biological activities. http://togogenome.org/gene/10090:Apcs ^@ http://purl.uniprot.org/uniprot/P12246|||http://purl.uniprot.org/uniprot/Q4JFI8 ^@ Cofactor|||Disease Annotation|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pentraxin family.|||Binds 2 calcium ions per subunit.|||Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.|||Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits.|||SAP is a precursor of amyloid component P which is found in basement membrane and associated with amyloid deposits.|||Secreted http://togogenome.org/gene/10090:Pals2 ^@ http://purl.uniprot.org/uniprot/B9EHZ5|||http://purl.uniprot.org/uniprot/Q3UN60|||http://purl.uniprot.org/uniprot/Q9JLB0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAGUK family.|||Interacts with CADM1. Interacts with the LIN7 proteins.|||Membrane http://togogenome.org/gene/10090:Tbl3 ^@ http://purl.uniprot.org/uniprot/Q8C4J7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Mbip ^@ http://purl.uniprot.org/uniprot/Q99LQ1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1. In the complex, it probably interacts directly with KAT2A, KAT14 and WDR5.|||Cytoplasm|||Inhibits the MAP3K12 activity to induce the activation of the JNK/SAPK pathway. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.|||Nucleus http://togogenome.org/gene/10090:Ddx19a ^@ http://purl.uniprot.org/uniprot/Q61655 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-dependent RNA helicase involved in mRNA export from the nucleus. Rather than unwinding RNA duplexes, DDX19 functions as a remodeler of ribonucleoprotein particles, whereby proteins bound to nuclear mRNA are dissociated and replaced by cytoplasmic mRNA binding proteins.|||Belongs to the DEAD box helicase family. DDX19/DBP5 subfamily.|||Cytoplasm|||Found in testis, heart, brain, liver, skeletal muscle, and kidney.|||The N-terminal extension helix acts as an autoinhibitory domain, preventing ATP hydrolysis, unless the N-terminus of the protein is displaced by RNA binding, allowing cleft closure to bring key side chains into position for catalysis.|||nucleoplasm http://togogenome.org/gene/10090:Tex43 ^@ http://purl.uniprot.org/uniprot/Q9D9I1 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed predominantly in the testis.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme, which is required for flagellum beating. May serve to reinforce and thus stabilize the microtubule structure in the sperm flagella (By similarity). Involved in the regulation of sperm motility (PubMed:34446558).|||No defects seen in the sperm morphology and the percentage of motile spermatozoa is comparable (PubMed:34446558). Howevwer, velocity parameters such as average path velocity, straight-line velocity, and curvilinear velocity are slightly decreased in the spermatozoa (PubMed:34446558).|||cilium axoneme http://togogenome.org/gene/10090:Rab1b ^@ http://purl.uniprot.org/uniprot/Q9D1G1 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasm|||Interacts with MICAL1 and MICAL2. Interacts (GTP-bound form) with MICALCL, MICAL1 and MILCAL3. Interacts with GDI1; the interaction requires the GDP-bound state. Interacts with CHM/REP1; the interaction requires the GDP-bound form and is necessary for prenylation by GGTase II. Interacts with RabGAP TBC1D20 (By similarity). Interacts (in GDP-bound form) with lipid phosphatase MTMR6 (via GRAM domain); the interaction regulates MTMR6 recruitment to the endoplasmic reticulum-Golgi intermediate compartment (PubMed:23188820). Interacts (in GDP-bound form) with lipid phosphatase MTMR7 (PubMed:23188820).|||Membrane|||Preautophagosomal structure membrane|||Prenylated; by GGTase II, only after interaction of the substrate with Rab escort protein 1 (REP1).|||Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP).|||Rab-1B binds GTP and GDP and possesses intrinsic GTPase activity.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). Plays a role in the initial events of the autophagic vacuole development which take place at specialized regions of the endoplasmic reticulum (By similarity). Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments. Required to modulate the compacted morphology of the Golgi. Promotes the recruitment of lipid phosphatase MTMR6 to the endoplasmic reticulum-Golgi intermediate compartment (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Cbfa2t2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1D5|||http://purl.uniprot.org/uniprot/O70374 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CBFA2T family.|||Expressed in embryonic stem cells.|||First expression detected on embryonic day 11.5.|||Homooligomer. Homotetramerization is mediated by the NHR2 domain. Interacts with CBFA2T3/MTG16 (PubMed:19799863). Can interact with RUNX1T1/CBFA2T1. Heterotetramerization between members of the CBFA2T family is proposed (By similarity). Interacts with RBP, GFI1, TCF4, PRDM14 (PubMed:25398765, PubMed:18039847, PubMed:27281218). Interacts with TAL1 and CBFA2T3/MTG16; the heteromer with CBFA2T3/MTG16 may function in repression of TAL1 (PubMed:19799863).|||Loss of Mtgr1 impairs the maturation of secretory cells in the small intestine.|||Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure.|||Nucleus|||Required for tumorigenesis in a AOM/DSS colitis-associated carcinoma model. May be involved in intestinal tumorigenesis.|||Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Via association with PRDM14 is involved in regulation of embryonic stem cell (ESC) pluripotency. Involved in primordial germ cell (PCG) formation (PubMed:27281218). Stabilizes PRDM14 and OCT4 on chromatin in a homooligomerization-dependent mannerCan repress the expression of MMP7 in a ZBTB33-dependent manner (By similarity). Through heteromerization with CBFA2T3/MTG16 may be involved in regulation of the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (PubMed:19799863). Required for the maintenance of the secretory cell lineage in the small intestine (PubMed:16227606). Can inhibit Notch signaling probably by association with RBPJ and may be involved in GFI1-mediated Paneth cell differentiation (PubMed:25398765). http://togogenome.org/gene/10090:Cntln ^@ http://purl.uniprot.org/uniprot/A2AM05 ^@ Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Interacts with CEP250 and CEP68. Interacts with NEK2; the interaction leads to phosphorylation of CNTLN.|||Phosphorylated directly or indirectly by NEK2.|||Required for centrosome cohesion and recruitment of CEP68 to centrosomes.|||centriole http://togogenome.org/gene/10090:Mpv17l2 ^@ http://purl.uniprot.org/uniprot/Q8VIK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxisomal membrane protein PXMP2/4 family.|||Interacts with the large mitochondrial ribosomal subunit.|||Membrane|||Mitochondrion inner membrane|||Required for the assembly and stability of the mitochondrial ribosome (By similarity). Is a positive regulator of mitochondrial protein synthesis (By similarity). http://togogenome.org/gene/10090:Lce1i ^@ http://purl.uniprot.org/uniprot/Q9D6P5 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Tmprss4 ^@ http://purl.uniprot.org/uniprot/Q8VCA5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Plasma membrane-anchored serine protease that directly induces processing of pro-uPA/PLAU into the active form through proteolytic activity (By similarity). Seems to be capable of activating ENaC (PubMed:12149280).|||Proteolytically processed; probably by an autocatalytic mechanism.|||Secreted http://togogenome.org/gene/10090:Ppm1n ^@ http://purl.uniprot.org/uniprot/Q8BGL1 ^@ Cofactor|||Similarity ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit. http://togogenome.org/gene/10090:Or52z12 ^@ http://purl.uniprot.org/uniprot/Q8VGA1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam83d ^@ http://purl.uniprot.org/uniprot/Q9D7I8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM83 family.|||Cytoplasm|||Interacts with FBXW7; promotes FBXW7 degradation (By similarity). May interact with RAF1 (By similarity). Interacts with KIF22; recruits KIF22 to mitotic spindle microtubules (By similarity). Interacts (via C-terminus) with DYNLL1 (By similarity). Interacts with HMMR (By similarity). Interacts (via N-terminus) with CSNK1A1/CK1a; in mitotic cells (By similarity).|||Phosphorylated during mitosis.|||Through the degradation of FBXW7, may act indirectly on the expression and downstream signaling of MTOR, JUN and MYC (By similarity). May play also a role in cell proliferation through activation of the ERK1/ERK2 signaling cascade (By similarity). May also be important for proper chromosome congression and alignment during mitosis through its interaction with KIF22 (By similarity).|||spindle|||spindle pole http://togogenome.org/gene/10090:Nppc ^@ http://purl.uniprot.org/uniprot/Q544K5|||http://purl.uniprot.org/uniprot/Q61839 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the natriuretic peptide family.|||Degraded by IDE (in vitro).|||Hormone which plays a role in endochondral ossification through regulation of cartilaginous growth plate chondrocytes proliferation and differentiation (PubMed:11259675). May also be vasoactive and natriuretic (By similarity). Acts by specifically binding and stimulating NPR2 to produce cGMP (PubMed:12890708). Binds the clearance receptor NPR3 (By similarity).|||Mice are viable perinatally but less than half survive postnatally due to skeletal abnormalities. They display severe dwarfism which is the consequence of a defect in endochondral ossification.|||Secreted http://togogenome.org/gene/10090:Mob4 ^@ http://purl.uniprot.org/uniprot/Q6PEB6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MOB1/phocein family.|||Binds STRN4 (By similarity). Interacts with DNM1 and EPS15 (By similarity). Interacts with nucleoside diphosphate kinase (By similarity). Binds STRN and STRN3. Part of a ternary complex containing MOB4/PHOCN, STRN and/or STRN3 and PPA2. Interacts with CTTNBP2 and CTTNBP2NL (By similarity).|||Golgi stack membrane|||May play a role in membrane trafficking, specifically in membrane budding reactions.|||Membrane|||Phosphorylated on serine residues.|||perinuclear region http://togogenome.org/gene/10090:Kcnh5 ^@ http://purl.uniprot.org/uniprot/Q920E3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.2/KCNH5 sub-subfamily.|||Membrane|||Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a non-inactivating outward rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly.|||The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH1/EAG (By similarity).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Brme1 ^@ http://purl.uniprot.org/uniprot/Q6DIA7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expressed in fetal ovaries but not in adult ovaries.|||Expressed in testis.|||Interacts with HSF2BP (via N-terminus) and BRCA2; the interaction with HSF2BP is direct and allows the formation of a ternary complex (PubMed:32345962, PubMed:32460033, PubMed:32463460, PubMed:32845237). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (PubMed:32345962).|||Male mutants are infertile (PubMed:32463460, PubMed:32460033, PubMed:32345962). They have smaller-than-normal testes with reduced diameters of seminiferous tubules and sperm density (PubMed:32460033, PubMed:32345962). Female mutants exhibit normal fertility with no apparent defect in adult ovaries (PubMed:32460033, PubMed:32345962). They show a strong reduction of the follicle pool.|||Meiotic recombination factor component of recombination bridges involved in meiotic double-strand break repair (PubMed:32463460, PubMed:32460033). Modulates the localization of recombinases DMC1:RAD51 to meiotic double-strand break (DSB) sites through the interaction with and stabilization of the BRCA2:HSF2BP complex during meiotic recombination (PubMed:32460033, PubMed:32463460). Indispensable for the DSB repair, homologous synapsis, and crossover formation that are needed for progression past metaphase I, is essential for spermatogenesis and male fertility (PubMed:32463460, PubMed:32460033). http://togogenome.org/gene/10090:Rab9b ^@ http://purl.uniprot.org/uniprot/Q3KNA5|||http://purl.uniprot.org/uniprot/Q8BHH2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Interacts (GTP-bound form) with SGSM1; the GDP-bound form has much lower affinity for SGSM1 (PubMed:25220469). The GTP-bound form but not the GDP-bound form interacts with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4) but does not interact with HPS1 alone (By similarity).|||Involved in the transport of proteins between the endosomes and the trans Golgi network.|||Membrane|||phagosome membrane http://togogenome.org/gene/10090:Map3k6 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ82 ^@ Similarity ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. http://togogenome.org/gene/10090:Rpl26 ^@ http://purl.uniprot.org/uniprot/P61255|||http://purl.uniprot.org/uniprot/Q4FZH2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL24 family.|||Component of the large ribosomal subunit (PubMed:26100019, PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:26100019, PubMed:36517592).|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with DHX33 (PubMed:26100019).|||Cytoplasm|||Ufmylated by UFL1 in response to endoplasmic reticulum stress, promoting reticulophagy of endoplasmic reticulum sheets.|||Up-regulated in silica-treated macrophages. http://togogenome.org/gene/10090:Vmn2r78 ^@ http://purl.uniprot.org/uniprot/K7N6U5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ctsc ^@ http://purl.uniprot.org/uniprot/P97821|||http://purl.uniprot.org/uniprot/Q3UBY5|||http://purl.uniprot.org/uniprot/Q8BQL3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Binds 1 Cl(-) ion per heavy chain.|||Broadly distributed, but higher levels found in lung, liver, kidney and spleen. Lower levels found in testis and brain.|||Lysosome|||Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains.|||Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. http://togogenome.org/gene/10090:Tssk5 ^@ http://purl.uniprot.org/uniprot/Q8C1R0 ^@ Activity Regulation|||Function|||PTM|||Similarity ^@ Activated by phosphorylation on Thr-207, potentially by autophosphorylation.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||May be involved in a signaling pathway during male germ cell development or mature sperm function. http://togogenome.org/gene/10090:Zfp292 ^@ http://purl.uniprot.org/uniprot/Q9Z2U2 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Contaminating sequence. Potential poly-A sequence.|||Expressed in postnatal day 1 (P1) pituitary. Also detected in presomatotrophic cell line GHFT1-5.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Dhx9 ^@ http://purl.uniprot.org/uniprot/A0A087WPL5|||http://purl.uniprot.org/uniprot/O70133 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active) (PubMed:22767893). Associates (via DRBM domains) with the RISC complex; this association occurs in a small interfering (siRNA)-dependent manner. Associates with the SMN complex; this association induces recruitment of DHX9 to the RNA polymerase II. Associates with polysomes in a LIN28A-dependent manner. Interacts (via C-terminus) with ACTB; this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes (By similarity). Interacts with ADAR isoform 1; this interaction occurs in a RNA-independent manner (PubMed:28355180). Interacts (via DRBM domains) with AGO2 (via middle region); this interaction promotes active RISC assembly by promoting the association of siRNA with AGO2. Interacts (via NTD domain) with AKAP8L (via N-terminus). Interacts with BRCA1 (via C-terminus); this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme. Interacts (via N-terminus) with CREBBP; this interaction mediates association with RNA polymerase II holoenzyme and stimulates CREB-dependent transcriptional activation (By similarity). Interacts (via N-terminus) with EIF2AK2/PKR; this interaction is dependent upon the activation of the kinase (PubMed:19229320). Interacts (via DRBM domains) with DICER1. Interacts with H2AX; this interaction is direct, requires phosphorylation of histone H2AX on 'Ser-140' by PRKDC and promotes binding of DHX9 to transcriptionally stalled sites on chromosomal DNA in response to genotoxic stress. Interacts with HNRNPC; this interaction is direct, enhanced probably by their concomitant binding to RNA and mediates the attachment to actin filaments. Interacts (via NTD domain) with PRMT1. Interacts with IGF2BP1. Interacts with IGF2BP2, IGF2BP3. Interacts (via DRBM domains) with ILF3; this interaction occurs in a RNA-independent manner. Interacts with Importin alpha/Importin beta receptor. Interacts with LARP6 (via C-terminus); this interaction occurs in a mRNA-independent manner. Interacts (via N- and C-terminus) with LIN28A (via C-terminus); this interaction occurs in a RNA-independent manner. Interacts with LMX1B. Interacts (via helicase C-terminal domain, HA2 and OB-fold regions) with MAVS (via CARD domain); this interaction occurs in both resting and double-stranded RNA poly(I:C)-induced cells. Interacts with MBD2; this interaction stimulates transcriptional activation in a CREB-dependent manner. Interacts (via H2A and OB-fold regions) with MYD88 (via TIR domain); this interaction is direct. Interacts with NLRP9 upon rotavirus infection; this interaction may trigger NLRP9 inflammasome activation and inflammatory response. Interacts (via DRBM, OB-fold and RGG regions) with NUP98 (via N-terminus); this interaction occurs in a RNA-dependent manner and stimulates DHX9-mediated ATPase activity and regulates transcription and splicing of a subset of genes. Interacts (via N-terminus) with NXF1 (via N-terminus); this interaction is direct and negatively regulates NXF1-mediated nuclear export of constitutive transport element (CTE)-containing cellular mRNAs. Interacts with RELA; this interaction is direct and activates NF-kappa-B-mediated transcription. Interacts (via MTAD region) with RNA polymerase II holoenzyme; this interaction stimulates transcription activation in a CREB-dependent manner. Interacts (via RGG region) with SMN1; this interaction links SMN1 to the RNA polymerase II holoenzyme (By similarity). Interacts with SP7 (PubMed:17303075). Interacts (via DRBM domains) with TARBP2 (via DRBM first and second domains); this interaction occurs in a small interfering (siRNA)-dependent manner. Interacts with TOP2A; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity. Interacts (via DRBM domains and C-terminus) with WRN (via 3'-5' exonuclease domain); this interaction inhibits the DNA-dependent NTPase and DNA helicase activities of DHX9 and stimulates the 3'-5' exonuclease activity of WRN. Interacts with XRCC5; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with ZIC2 (via C2H2-type domain 3) (PubMed:17251188). Interacts with MCM3AP (By similarity).|||Cytoplasm|||DRBM domains cooperate for the binding to nucleic acid but not for unwinding helicase activity. The helicase-associated domain-2 (HA2) region is essential for the duplex RNA unwinding helicase activity. The minimal transactivation region (MTAD) mediates interaction with the RNA polymerase II holoenzyme and stimulates transcriptional activation in a CREB-dependent manner. The oligonucleotide- or oligosaccharide-binding (OB-fold) and the repeated arginine and glycine-glycine (RGG) regions are dispensable for both RNA-binding and unwinding helicase activities. The RGG region contains both nuclear localization signal (NLS) and nuclear export signal (NES) and is necessary and sufficient for nucleocytoplasmic shuttling in a RNA-independent manner.|||Intron retention.|||Methylated. PRMT1-mediated methylation of undefined Arg residues in the nuclear transport domain (NTD) is required for nuclear import of DHX9.|||Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing. Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA- and RNA-based G-quadruplexes. Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA. Binds also to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A. Plays a role in DNA replication at origins of replication and cell cycle progression. Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1. Binds to the CDKN2A promoter. Plays several roles in post-transcriptional regulation of gene expression. In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (By similarity). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (PubMed:22767893). Acts also as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA. Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability. Plays a role in mRNA translation. Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs. Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation. Also plays a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process. Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (By similarity).|||Nucleus|||Phosphorylated by PRKDC; phosphorylation occurs in a RNA-dependent manner. Phosphorylated by EIF2AK2/PKR; this phosphorylation reduces its association with double-stranded RNA.|||centrosome|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Adsl ^@ http://purl.uniprot.org/uniprot/P54822 ^@ Function|||Similarity|||Subunit ^@ Belongs to the lyase 1 family. Adenylosuccinate lyase subfamily.|||Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate.|||Homotetramer. Residues from neighboring subunits contribute catalytic and substrate-binding residues to each active site. http://togogenome.org/gene/10090:Zmynd10 ^@ http://purl.uniprot.org/uniprot/Q99ML0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ZMYND10 family.|||Cytoplasm|||Dynein axonemal particle|||Expressed in the testis. Expressed in the tracheal epithelium (PubMed:29601588). Restricted to regions containing motile cilia (PubMed:23891471).|||Interacts (via C-terminus) with DNAAF11 (via CS domain); this interaction stabilizes DNAAF11 at the protein level. Interacts (via C-terminus) with DNAL1; this interaction stabilizes DNAL1 at the protein level. Interacts with DNAAF4, HSPA8, IQUB, RUVBL2 and DYNTL5.|||Mice neonates exhibit growth retardation dying within 1 month after birth. Show head deformation and situs invertus (heart apex, stomach, liver or spleen). Display lung lobular structures deterioration and collapsed alveolar spaces. Show mucosal congestion in paranasal cavities. Show loss of ciliary motility and axonemal outer and inner dynein arm (IDA and ODA, respectively) components without disruption of ciliogenesis.|||Plays a role in axonemal structure organization and motility (PubMed:29601588). Involved in axonemal pre-assembly of inner and outer dynein arms (IDA and ODA, respectively) for proper axoneme building for cilia motility (PubMed:29601588). May act by indirectly regulating transcription of dynein proteins (By similarity).|||Specifically expressed in the ciliated epithelial layer associated with nasal and lung epithelium in 18.5 dpc embryos.|||centriolar satellite http://togogenome.org/gene/10090:Asic2 ^@ http://purl.uniprot.org/uniprot/B2RRQ1|||http://purl.uniprot.org/uniprot/Q3UYD3|||http://purl.uniprot.org/uniprot/Q925H0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC2 subfamily.|||Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.|||Cell membrane|||Expressed by sensory neurons. Expressed by nociceptive sensory neurons, spiral ganglion (SG) neurons and the retina (at protein level). Isoform 1 and isoform 2 are expressed in outer nuclear layer of retina (photoreceptors) and to a lower extent in distal and proximal inner nuclear layer.|||Expression changes dramatically during cochlear development. Expression is detected at 11.5 dpc in otocyst and increases in the SG neurons after 18.5 dpc. Also detected in the lumen side of all cells forming the vestibular cavity and at the top of the macula of saccule and utricle. Before birth expressed by epithelial cells facing the endolymphatic space. Post-natally expressed by cells in the apical turn of the cochlea, while expression on the lumen side of the membranous labyrinth decreases. Expression shifts gradually toward the top of supporting cells and the spiral limbus. Also expressed by vestibular ganglion neurons. Restricted to the SG neurons in the mature cochlea (at protein level).|||Expression in a subset of neurons may be regulated by neurotrophins.|||Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with PRKCABP and ASIC3 (By similarity). Interacts with STOM; this regulates channel activity (PubMed:15471860, PubMed:22850675). Heterotrimer of Asic1a-Asic2a interacts with the snake venom mambalgin-1, mambalgin-2 and mambalgin-3 (By similarity). Heterotrimer of Asic1a-Asic2b interacts with the snake venom mambalgin-1 and mambalgin-2 (By similarity).|||Membrane|||Mice display altered rod phototransduction and neurotransmission, associated with increased light-induced retina damages.|||Regulated by Zn(2+). Inhibited by anti-inflammatory drugs like salicylic acid (By similarity). http://togogenome.org/gene/10090:Crb1 ^@ http://purl.uniprot.org/uniprot/A0A7D6VMF7|||http://purl.uniprot.org/uniprot/A0A7D6VRP0|||http://purl.uniprot.org/uniprot/Q8VHS2 ^@ Caution|||Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the Crumbs protein family.|||Component of a complex composed of PALS1, CRB1 and EPB41L5 (By similarity). Within the complex, interacts (via intracellular domain) with PALS1 and EPB41L5 (via FERM domain) (By similarity). Forms a complex with MPP4 and PALS1 (PubMed:15316081). Interacts with MPDZ/MUPP1 and MPP4 (PubMed:15316081).|||Cytoplasm|||Defects in Crb1 are a cause of focal retinal dysplasia and degeneration associated with a shortening of inner and outer segments. Affected mice produce a secreted truncated protein that lacks the single transmembrane and the intracellular domain, and develop irregularities at the outer limiting membrane and loss of photoreceptor cells.|||Expressed in the kidney, lung, stomach and testis (PubMed:14684155). Expressed in the brain (PubMed:11744384, PubMed:14684155). Expressed in the retina of the eye (PubMed:11744384, PubMed:14684155, PubMed:26404741). Expressed in the outer nuclear layer, photoreceptor layer and inner nuclear layer of the retina (PubMed:11744384). Expressed in Mueller cell radial processes in the inner nuclear layer, in apical processes sclerad to the external limiting membrane, and in the subapical region, adjacent to the adherens junction of retinal photoreceptors (PubMed:12915475, PubMed:15316081). In the brain, expressed in the granular layer of the cerebellum, the hippocampal dentate gyrus, the olfactory bulbs, the subventricular region lining the telencephalic ventricles and the rostral migratory stream (PubMed:11744384).|||Expression first detected at 14 dpc, expression is enhanced at 15 and 16 dpc during active proliferation of epidermal cells, decreases after birth, but is maintained in adult skin (PubMed:14684155). Detected in the skin basal cells at 16 dpc, it was observed in upper layers after birth (at protein level) (PubMed:14684155).|||Glycosylated.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play a role in epidermal tissue morphogenesis (PubMed:14684155). May function in cell attachment for stratified epithelial organization (PubMed:14684155).|||Photoreceptor inner segment|||Plays a role in photoreceptor morphogenesis in the retina (PubMed:12915475). May maintain cell polarization and adhesion (PubMed:15316081).|||Primarily detected in the central nervous system at 10.5 dpc, in the ventral part of the neural tube including the ventral spinal cord, the ventral part of the mesencephalon, the mammillary and the hypothalamic regions, the optic area and the zona limitans intrathalamica (PubMed:11744384). Expressed by the V3 interneurons placed between the floor plate and the motorneurons all along the spinal cord axis (PubMed:11744384). In late embryogenesis, expressed mainly in ventral neural structures of the developing brain, including the mammillary, tuberalis regions of the hypothalamus and the preoptic area (PubMed:11744384). Starting from 12.5 dpc, also strongly expressed in the neural area that gives rise to the dorsal thalamus (PubMed:11744384). In the retina, expression starts at 11.5 dpc and is enhanced at 12.5, 14.5 and 16.5 dpc (PubMed:11744384). Expressed in the subapical region of the neuroepithelial layer of the retina at 17.5 dpc (PubMed:23001562). In postnatal stages, abundant expression in photoreceptors and also found in the inner nuclear layer and iris (PubMed:11744384).|||Secreted|||Ubiquitously expressed.|||focal adhesion|||photoreceptor outer segment http://togogenome.org/gene/10090:Ccnt2 ^@ http://purl.uniprot.org/uniprot/Q7TQK0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family. Cyclin C subfamily.|||Expressed in all forming organs and supporting tissues in 10.5 to 14.5 dpc. Expressed in embryonic ectoderm and the forming brain and neural tube in 7.5 and 8.5/9.5 dpc embryos, respectively.|||Highly expressed in all phases of skeletal muscle differentiation, particularly in later stages (PubMed:23060074). Highly expressed in skeletal muscle. Significantly expressed in heart, brain, kidney, liver, testis, and pancreas (PubMed:19364821).|||Interacts with CDK9 to form P-TEFb. Interacts with POLR2A (via the C-terminal domain (CTD)); mediates transcriptional activity. Interacts with HEXIM1; mediates formation of a tripartite complex with KPNA2. Interacts with HEXIM2. Interacts with PKN1; enhances MYOD1-dependent transcription. P-TEFB complex interacts with RB1; promotes phosphorylation of RB1 (By similarity). P-TEFB complex interacts with MYOD1; promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation (PubMed:12037670). Interacts with MDFI and MDFIC (By similarity).|||Nucleus|||Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFB), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNAP II). The activity of this complex is regulated by binding with 7SK snRNA (By similarity). Plays a role during muscle differentiation; P-TEFB complex interacts with MYOD1; this tripartite complex promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation and binds the chromatin of promoters and enhancers of muscle-specific genes; this event correlates with hyperphosphorylation of the CTD domain of RNA pol II (PubMed:16245309, PubMed:23060074, PubMed:12037670). In addition, enhances MYOD1-dependent transcription through interaction with PKN1 (By similarity). Involved in early embryo development (PubMed:19364821).|||The homozygous knockout of Ccnt2 is embryonic lethal.|||perinuclear region http://togogenome.org/gene/10090:Kif2a ^@ http://purl.uniprot.org/uniprot/P28740|||http://purl.uniprot.org/uniprot/Q9D481 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. MCAK/KIF2 subfamily.|||Cytoplasm|||Highest level in lung. High level in ovary, moderate levels in heart, kidney, placenta, skeletal muscle and spleen (at protein level). Pancreas and spleen express a shorter isoform (at protein level). Expressed in the flagellum of elongated spermatids and sperm in the testis lumen (at protein level) (PubMed:24339785). Isoform 1 expressed in neuronal cells. Isoform 2 expressed in astrocytes and fibroblasts.|||Interacts with AURKA, PSRC1 and PLK1.|||Isoform 1 expressed at low level in 13 dpc embryonic hippocampus, higher level by stage 15 persisting into juvenile and adult stages. Isoform 2 expressed in 13 dpc and 15 dpc embryonic hippocampus declining to very low levels in juvenile and adult neurons. High level of isoform 1 and very low level of isoform 2 in stage 2 and 5 hippocampal neurons in culture.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lysosome|||Mice show overextension of collateral branches of developing axons and defects in neuronal migration in the brain. They die within 24 hours of birth.|||Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity (By similarity).|||centrosome|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Foxj1 ^@ http://purl.uniprot.org/uniprot/Q61660|||http://purl.uniprot.org/uniprot/Q640Q8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FOXJ1 family.|||Expressed in the developing fetal lung epithelium and developing brain (at protein level).|||Mice lack motile respiratory tract cilia and exhibit randomization of the left-right body axis due to loss of motile cilia in the embryonic node (PubMed:9739041, PubMed:10873152). Motile type cilia with a '9 + 2' microtubule ultrastructure are absent in epithelial cells, including those in the airways (PubMed:10873152).|||Nucleus|||Predominantly expressed in tissues containing motile cilia.|||Transcription factor specifically required for the formation of motile cilia (PubMed:9096351, PubMed:9739041, PubMed:10873152, PubMed:14996907, PubMed:22357932, PubMed:27965440). Acts by activating transcription of genes that mediate assembly of motile cilia, such as CFAP157 (PubMed:27965440). Binds the DNA consensus sequences 5'-HWDTGTTTGTTTA-3' or 5'-KTTTGTTGTTKTW-3' (where H is not G, W is A or T, D is not C, and K is G or T) (PubMed:9096351). Activates the transcription of a variety of ciliary proteins in the developing brain and lung (PubMed:28666954, PubMed:27914912). http://togogenome.org/gene/10090:Gm20793 ^@ http://purl.uniprot.org/uniprot/Q3TTD8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Clec12b ^@ http://purl.uniprot.org/uniprot/A0A0R4J0A7|||http://purl.uniprot.org/uniprot/Q149M0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Homodimer. Interacts (via ITIM motif) with PTPN6. Interacts (via ITIM motif) with PTPN11; this interaction triggers dephosphorylation and activation of PTPN11.|||Inhibitory receptor postulated to negatively regulate immune and non-immune functions (By similarity). Upon phosphorylation, recruits SH2 domain-containing PTPN6 and PTPN11 phosphatases to its ITIM motif and antagonizes activation signals (By similarity). Although it inhibits KLRK1/NKG2D-mediated signaling, it does not bind known ligands of KLRK1/NKG2D and therefore is not its inhibitory counterpart (By similarity). May limit activation of myeloid cell subsets in response to infection or tissue inflammation (By similarity). May protect target cells against natural killer cell-mediated lysis (By similarity). May negatively regulate cell cycle and differentiation of melanocytes via inactivation of STAT3 (By similarity).|||Membrane http://togogenome.org/gene/10090:Catip ^@ http://purl.uniprot.org/uniprot/B9EKE5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CATIP family.|||Cell membrane|||Cytoplasm|||Interacts with TTC17.|||Nucleus|||Plays a role in primary ciliogenesis by modulating actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Cln5 ^@ http://purl.uniprot.org/uniprot/B2RUP8|||http://purl.uniprot.org/uniprot/Q3UMW8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CLN5 family.|||Can undergo proteolytic cleavage at the C-terminus, probably by a cysteine protease and may involve the removal of approximately 10-15 residues from the C-terminal end (PubMed:26342652).|||Heart, kidney, liver, spleen, muscle and rectum (at protein level).|||Interacts with PPT1, TPP1, CLN3, CLN6, CLN8, ATP5F1A and ATP5F1B (PubMed:19941651). Interacts with SORT1, RAB5A and RAB7A (By similarity).|||Lysosome|||Membrane|||N-glycosylated with both high mannose and complex type sugars. Glycosylation is important for proper folding and trafficking to the lysosomes.|||Plays a role in influencing the retrograde trafficking of lysosomal sorting receptors SORT1 and IGF2R from the endosomes to the trans-Golgi network by controlling the recruitment of retromer complex to the endosomal membrane. Regulates the localization and activation of RAB7A which is required to recruit the retromer complex to the endosomal membrane.|||The type II membrane signal anchor is proteolytically cleaved to produce a mature form that is transported to the lysosomes (Ceroid-lipofuscinosis neuronal protein 5 homolog, secreted form). http://togogenome.org/gene/10090:Cplx3 ^@ http://purl.uniprot.org/uniprot/Q8R1B5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the complexin/synaphin family.|||Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.|||Cell membrane|||Complexin that regulates SNARE protein complex-mediated synaptic vesicle fusion (PubMed:19386896). Required for the maintenance of synaptic ultrastructure in the adult retina (PubMed:19386896). Positively regulates synaptic transmission through synaptic vesicle availability and exocytosis of neurotransmitters at photoreceptor ribbon synapses in the retina (PubMed:15911881, PubMed:19386896, PubMed:27335398). Suppresses tonic photoreceptor activity and baseline 'noise' by suppression of Ca(2+) vesicle tonic release and the facilitation of evoked synchronous and asynchronous Ca(2+) vesicle release (PubMed:22694764, PubMed:27335398).|||Farnesylation mediates presynaptic targeting.|||In the brain, expression starts at P6 and increases to reach a plateau at P20.|||Knockout mice are generally phenotypically normal, viable, and fertile (PubMed:19386896). Normal overall retina structure and morphology of the outer plexiform layer (OPL) and inner plexiform layer (IPL) (PubMed:19386896). Abundance and distribution of synaptic proteins remain consistent (PubMed:19386896). Reduced retinal synaptic transmission and inner retinal processing (PubMed:19386896). Cplx3 and Cplx4 double knockout mice are generally phenotypically normal, viable, and fertile, however show disordered morphology of the OPL and vision perturbation when compared to single knockout mice (PubMed:19386896). Cplx3 and Cplx4 double knockout mice show evidence of mild vision perturbation, with a reduction in the number of morphologically normal anchored presynaptic ribbon synapses and a decrease in controlled neurotransmitter release at photoreceptor ribbon synapses (PubMed:19386896). Cplx3 and Cplx4 double knockout mice show reduced response and sensitivity of ON and OFF ganglion cell response as a result of disrupted synaptic transmission (PubMed:22694764). Cplx3 and Cplx4 double knockout mice show a greater variance in photoreceptor activity response and a decrease in sustained response, this is caused by an increase in release and fusion of synaptic vesicles in an asynchronous manner, this is particularly evident following multiple stimuli (PubMed:27335398).|||Present in many brain regions, including hippocampus and cerebellum (at protein level) (PubMed:15911881). Expressed in the retina (at protein level) (PubMed:15911881, PubMed:19386896). Expressed in retinal amacrine cells (at protein level) (PubMed:19386896, PubMed:22694764). Expressed in retinal photoreceptor ribbon synapses (PubMed:19386896). Expressed in the retinal inner nuclear layer, at bipolar cells (at protein level) (PubMed:22694764). Expressed in cone photoreceptor synaptic terminals (at protein level) (PubMed:22694764).|||Synapse http://togogenome.org/gene/10090:Tspan14 ^@ http://purl.uniprot.org/uniprot/Q8QZY6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Interacts with ADAM10; the interaction promotes ADAM10 maturation and cell surface expression.|||Regulates maturation and trafficking of the transmembrane metalloprotease ADAM10 (PubMed:26668317, PubMed:23035126). Negatively regulates ADAM10-mediated cleavage of GP6 (PubMed:26668317). Promotes ADAM10-mediated cleavage of CDH5 (PubMed:23035126). http://togogenome.org/gene/10090:Ccs ^@ http://purl.uniprot.org/uniprot/Q543K2|||http://purl.uniprot.org/uniprot/Q9WU84 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Binds 2 copper ions per subunit.|||Cytoplasm|||Delivers copper to copper zinc superoxide dismutase (SOD1).|||Homodimer, and heterodimer with SOD1. Interacts with COMMD1. Interacts with XIAP/BIRC4. Interacts with SLC31A1(via C-terminal domain); this interaction is Cu(1+)-mediated. The heterodimer CCS:SOD1 interacts with SLC31A1; this heterotrimer is Cu(1+)-mediated and its maintenance is regulated through SOD1 activation.|||In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family.|||Ubiquitinion by XIAP/BIRC4 leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. XIAP/BIRC4 preferentially ubiquitinates at Lys-241 (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Or51f23b ^@ http://purl.uniprot.org/uniprot/A0A1B0GSU5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Shcbp1l ^@ http://purl.uniprot.org/uniprot/Q3TTP0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in pachytene spermatocytes and elongating spermatids inside the seminiferous tubules (PubMed:24557841). Not detected in ovary (at protein level) (PubMed:24557841). Testis-specific (PubMed:24557841).|||Interacts with HSPA2; this interaction may promote the recruitment of HSPA2 to the spindle (PubMed:24557841).|||Male mice exhibit decreased fertility and produce reduced epididymal sperm content, but do not influence the rates of motility, capacitation and acrosome reaction of sperm (PubMed:24557841). Meiosis-arrested spermatocytes are increased in the early stages of meiosis and undergo programmed cell death (PubMed:24557841). Display a diminution of the HSPA2 signal at the spindle and disordered chromosomes during male meiosis (PubMed:24557841).|||Testis-specific spindle-associated factor that plays a role in spermatogenesis (PubMed:24557841). In association with HSPA2, participates in the maintenance of spindle integrity during meiosis in male germ cells (PubMed:24557841).|||spindle http://togogenome.org/gene/10090:Csf2 ^@ http://purl.uniprot.org/uniprot/P01587|||http://purl.uniprot.org/uniprot/Q5SX78 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GM-CSF family.|||Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.|||Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits (By similarity).|||Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits.|||Secreted http://togogenome.org/gene/10090:Kctd11 ^@ http://purl.uniprot.org/uniprot/Q8K485 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subunit|||Tissue Specificity ^@ Detected at 7.5 dpc in neuroectodermal cells, and later in neural crest, in ventral region of the spinal cord and in ventricular epithelium of the neural tube.|||Homopentamer. Interacts with KCTD6 and KCTD21; KCTD11 and KCTD6 or KCTD21 may associate in pentameric assemblies. Component of the BCR(KCTD11) E3 ubiquitin ligase complex, at least composed of CUL3 and KCTD11 and RBX1. Interacts (via BTB domain) with CUL3; initially a 4:4 stoichiometry has been reported, however, electron microscopy revealed pentameric states of the BTB domain.|||Overexpression of Kctd11 by lentiviral vector injection inhibits xenograft tumor growth in athymic nude mice.|||Plays a role as a marker and a regulator of neuronal differentiation; Up-regulated by a variety of neurogenic signals, such as retinoic acid, epidermal growth factor/EGF and NGFB/nerve growth factor. Induces apoptosis, growth arrest and the expression of cyclin-dependent kinase inhibitor CDKN1B. Plays a role as a tumor repressor and inhibits cell growth and tumorigenicity of medulloblastoma (MDB). Acts as probable substrate-specific adapter for a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex towards HDAC1. Functions as antagonist of the Hedgehog pathway on cell proliferation and differentiation by affecting the nuclear transfer of transcription factor GLI1, thus maintaining cerebellar granule cells in undifferentiated state, this effect probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. When knock-down, Hedgehog antagonism is impaired and proliferation of granule cells is sustained. Activates the caspase cascade.|||The BTB domain is required for growth-suppressing properties.|||Weakly expressed in lung. In the cerebellum, higher expression in non proliferating external granule cells layer than in highly proliferating ones. http://togogenome.org/gene/10090:Ctss ^@ http://purl.uniprot.org/uniprot/F6WR04|||http://purl.uniprot.org/uniprot/O70370|||http://purl.uniprot.org/uniprot/Q3UD32|||http://purl.uniprot.org/uniprot/Q8BSZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Lysosome|||Secreted|||Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules and MHC class II antigen presentation. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L.|||Widely expressed with highest expression found in non-skeletal tissues. Relatively high levels found in skeletal tissues. Expressed in spleen, B cells, dendritic cells and macrophages (PubMed:9545226).|||phagosome http://togogenome.org/gene/10090:Slc16a14 ^@ http://purl.uniprot.org/uniprot/Q8K1C7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Proton-linked monocarboxylate transporter. May catalyze the transport of monocarboxylates across the plasma membrane. http://togogenome.org/gene/10090:Ndfip1 ^@ http://purl.uniprot.org/uniprot/Q8R0W6 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (PubMed:11748237, PubMed:17137798, PubMed:20962770). Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551). Restricts the production of pro-inflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC (PubMed:28051111). Together with NDFIP2, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (PubMed:27088444). Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (PubMed:24520172, PubMed:28051111). Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (By similarity). Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus where it mediates KCNH2 degradation (By similarity). In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity (By similarity). Important for normal development of dendrites and dendritic spines in cortex (PubMed:23897647). Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046). Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (PubMed:25632008). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (By similarity). Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959).|||Endosome membrane|||Forms heterodimers with NDFIP2 (By similarity). Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2 (PubMed:11042109, PubMed:11748237, PubMed:17137798, PubMed:25632008). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion (PubMed:11748237). Interacts with U2SURP (PubMed:11748237). Interacts with SLC11A2/DMT1 (By similarity). Interacts with PTEN (By similarity). May interact with phosphorylated EGFR (By similarity). Interacts with BRAT1 (By similarity). Interacts with KCNH2 (By similarity). Interacts with MAVS (By similarity). Part of a complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH (PubMed:25632008).|||Golgi apparatus membrane|||Highly expressed in embryonic and early postnatal cortex (at protein level) (PubMed:23897647). Widely expressed (PubMed:11748237). Hardly detectable in resting T-cells; up-regulated in T-cells in response to activation (PubMed:17137798).|||Mutant mice appear normal at birth, but develop severe skin and gastrointestinal tract inflammation around 6 to 8 weeks of age (PubMed:17137798, PubMed:20962770). They do not survive beyond 14 weeks (PubMed:17137798). This phenotype is due to the lack of activity of ITCH E3 ubiquitin-protein ligase, and consequently, prolongation of JUNB half-life after T-cell activation (PubMed:17137798, PubMed:20962770). This results in an increased production of T-helper 2 (Th2) cytokines and in the promotion of Th2-mediated inflammation (PubMed:17137798, PubMed:20962770). This subsequently leads to increased number of circulating, esophagus and small bowel eosinophils (PubMed:20962770). Mutant mice have thicker small bowel and do not gain as much weight as the wild type (PubMed:20962770). Mutant mice also show an increased iron transport in hepatocytes and iron accumulation in the liver around portal veins, in the villi of duodenum and throughout the brain cortex (PubMed:18776082, PubMed:19706893).|||Secreted|||The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination.|||Ubiquitinated by NEDD4; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation.|||Undergoes transient tyrosine phosphorylation following EGF stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1 (By similarity).|||Up-regulated after traumatic brain injury in surviving neurons around the lesion site.|||dendrite|||synaptosome http://togogenome.org/gene/10090:Col2a1 ^@ http://purl.uniprot.org/uniprot/P28481 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibrillar collagen family.|||Contains 3-hydroxyproline at a few sites. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.|||Contains mostly 4-hydroxyproline. Prolines at the third position of the tripeptide repeating unit (G-X-P) are 4-hydroxylated in some or all of the chains.|||Defects in Col2a1 are the cause of a phenotype resembling human spondyloepiphyseal dysplasia congenita (sedc). Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora and tibias, and retinoschisis and hearing loss.|||Expressed in chondrogenic tissues in advance of chondrocyte differentiation. Expressed early in embryogenesis at 9.5 days both in the cranial mesenchyme destined for the chondrocranium, and the sclerotome of the somites, and at 12.5 days in the primordia of the hyoid and the laryngeal cartilage. Detected in all the chondrogenic tissues of the axial and appendicular skeleton until the onset of endochondral ossification. Expression also observed in non-chondrogenic tissues such as the notochord. Also expressed much later in the tail tendon, at 16.5-18.5 days. Transiently expressed in the heart at 9.5-12.5 days, the epidermis at 10.5-14.5 days, the calvarial mesenchyme at 12.5-16.5 days, the inner ear at 14.5 days and the fetal brain from 9.5-14.5 days. Within the neural tube, expression is localized to the proliferative ventricular cells of the forebrain and midbrain of 9.5-10.5 day embryos, and subsequently, restricted to the rhombencephalic basal plate, the ventricular layer of the hindbrain and the cervical spinal cord.|||Homotrimers of alpha 1(II) chains.|||Lysine residues at the third position of the tripeptide repeating unit (G-X-Y) are 5-hydroxylated in some or all of the chains.|||O-glycosylated on hydroxylated lysine residues. The O-linked glycan consists of a Glc-Gal disaccharide.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces.|||extracellular matrix http://togogenome.org/gene/10090:Gm20594 ^@ http://purl.uniprot.org/uniprot/J3QJY3 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Dbx2 ^@ http://purl.uniprot.org/uniprot/F8VQH7|||http://purl.uniprot.org/uniprot/Q8BZD0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Kcmf1 ^@ http://purl.uniprot.org/uniprot/Q80UY2 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Tissue Specificity ^@ Belongs to the KCMF1 family.|||Expressed throughout embryonic development, with much higher expression after day 15, when many organs including the kidney are undergoing extensive branching morphogenesis.|||Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination.|||Testis, liver, kidney, heart and skeletal muscle.|||Up-regulated during growth factor-induced branching tubulogenesis. http://togogenome.org/gene/10090:Mosmo ^@ http://purl.uniprot.org/uniprot/Q8C784 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Acts as a negative regulator of hedgehog signaling probably by promoting internalization and subsequent degradation of smoothened protein (SMO) present in the ciliary membrane (PubMed:29290584). Plays a role in sonic hedgehog (SHH)-induced spinal neural progenitor cells differentiation (PubMed:29290584).|||Cell membrane|||Expressed in the ventral neural tube at 11.5 dpc.|||cilium membrane http://togogenome.org/gene/10090:Tex261 ^@ http://purl.uniprot.org/uniprot/Q62302 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SVP26 family.|||Detected in testis.|||Membrane|||Not detectable in testis from 6 day old animals. Detectable in testis 15 days after birth. Highly expressed in testis 20 days after birth. Highly expressed in meiotic and post-meiotic germ cells. http://togogenome.org/gene/10090:Uba1 ^@ http://purl.uniprot.org/uniprot/A0A1S6GWH5|||http://purl.uniprot.org/uniprot/B9EHN0|||http://purl.uniprot.org/uniprot/Q02053 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-activating E1 family.|||Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1511901). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.|||Cytoplasm|||ISGylated.|||In testis, highly expressed from 14.5 days post coitum (dpc) until the day of birth, with levels falling after 10 days post partum (dpp) but peaking again at 28 dpp.|||May be modulated by the thyroid hormone receptor.|||Mitochondrion|||Monomer. Interacts with GAN (via BTB domain).|||Nucleus|||There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.|||Ubiquitously expressed. In testis, expressed in A spermatogonia and spermatids but at very low levels in pachytene spermatocytes. http://togogenome.org/gene/10090:Xrn1 ^@ http://purl.uniprot.org/uniprot/A0A087WQN7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the 5'-3' exonuclease family.|||Cytoplasm http://togogenome.org/gene/10090:Chdh ^@ http://purl.uniprot.org/uniprot/Q8BJ64 ^@ Disruption Phenotype|||PTM|||Similarity|||Subcellular Location Annotation ^@ Acetylation of Lys-498 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the GMC oxidoreductase family.|||Decreased testicular betaine and increased choline and phosphatidylcholine concentrations. Only one of eleven males was able to reproduce, impaired fertility was due to diminished sperm motility.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gm20867 ^@ http://purl.uniprot.org/uniprot/Q5FWD4 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Adam3 ^@ http://purl.uniprot.org/uniprot/F8VQ03|||http://purl.uniprot.org/uniprot/Q62287|||http://purl.uniprot.org/uniprot/Q810R6 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding of spermatozoa to the zona pellucida is significantly reduced in vitro, however oocyte fertilization was still able to occur.|||Cell membrane|||Expressed in sperm (at protein level).|||Initially synthesized as a 110-kDa precursor in round spermatids, and the precursor is then processed into a 42-kDa mature protein during the sperm transport into and/or once in the epididymis.|||Interacts with LY6K (PubMed:24501175). Interacts with TEX101 (PubMed:23633567).|||Involved in fertilization by controlling sperm migration into the oviduct (PubMed:19339711). Promotes the binding of sperm to the oocyte zona pellucida (PubMed:32529245).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||There are two genes in human, ADAM3A and ADAM3B that are non-functional (PubMed:11439107). ADAM3A gene is deleted in infertile men and in some fertile men. ADAM3B transcripts, from testicular RNA of ADAM3A-deficient men, present many stop codons in all possible reading frames. Moreover these two proteins are neither detected in extracts from the testis of a man with the ADAM3A-positive genotype, nor of a man with a ADAM3A-deficient genotype. http://togogenome.org/gene/10090:Ticam2 ^@ http://purl.uniprot.org/uniprot/Q8BJQ4 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Early endosome|||Endoplasmic reticulum|||Functions as sorting adapter in different signaling pathways to facilitate downstream signaling leading to type I interferon induction. In TLR4 signaling, physically bridges TLR4 and TICAM1 and functionally transmits signal to TICAM1 in early endosomes after endocytosis of TLR4. In TLR2 signaling, physically bridges TLR2 and MYD88 and is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement. Involved in IL-18 signaling and is proposed to function as a sorting adapter for MYD88 in IL-18 signaling during adaptive immune response. Forms a complex with RAB11FIP2 that is recruited to the phagosomes to promote the activation of the actin-regulatory GTPases RAC1 and CDC42 and subsequent phagocytosis of Gram-negative bacteria.|||Golgi apparatus|||Homodimer. Interacts with TLR4, TICAM1, IRF3 and IRF7 in response to LPS. Interacts with IL1R1, IL1RAP, IRAK2, IRAK3 and TRAF6. Interacts with protein kinase-inactive mutants of IRAK1 and IRAK4. Isoform 1 interacts with isoform 2; the interaction occurs in late endosomes and disrupts the interaction between isoform 1 and TICAM1. Interacts with MYD88; the interaction decreases after IL-18 stimulation in a time-dependent manner. Interacts with IL18R1 and IL18RAP. Interacts with TLR2. Interacts with RAB11FIP2.|||Late endosome|||Myristoylated. Required for membrane association which is critical for its ability to initiate efficient signaling.|||Phosphorylated by PRKCE in response to LPS. Phosphorylation is essential for its function. It is depleted from the membrane upon phosphorylation. Tyrosine phosphorylation is inhibited by phosphatase PTPN4.|||The TIR domain mediates the interaction with TRAF6 and MYD88.|||phagocytic cup http://togogenome.org/gene/10090:Ptgr3 ^@ http://purl.uniprot.org/uniprot/Q14AZ9|||http://purl.uniprot.org/uniprot/Q8BGC4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.|||Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest efficiency towards 15-keto-PGE2-alpha. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.|||Peroxisome|||Up-regulated by high fat diet (PubMed:19091015). Down-regulated in white adipose tissue in ob/on mice (PubMed:23821743).|||Widely expressed. http://togogenome.org/gene/10090:Adamts1 ^@ http://purl.uniprot.org/uniprot/P97857|||http://purl.uniprot.org/uniprot/Q3TQF7|||http://purl.uniprot.org/uniprot/Q3TTE6 ^@ Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Cleaves aggrecan, a cartilage proteoglycan, at the '1691-Glu-|-Leu-1692' site (within the chondroitin sulfate attachment domain), and may be involved in its turnover. Has angiogenic inhibitor activity (By similarity). Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture (By similarity).|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||In embryonic skeletal muscle, significantly increased levels between 13.5 dpc and 15.5 dpc with maximal expression observed at 15.5 dpc (PubMed:23233679). Decreased levels in postnatal skeletal muscle (PubMed:23233679). In myoblasts, up-regulated soon after induction of myoblast differentiation (PubMed:23233679).|||Induced in vitro in colon adenocarcinoma cells by interleukin-1, or in vivo in kidney and heart by lipopolysaccharide. Also induced by LH stimulation in granulosa cells of preovulatory follicles.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Tent5c ^@ http://purl.uniprot.org/uniprot/Q5SSF7 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals do not display major developmental phenotypes. They suffer from anemia with lower hemoglobin levels compared to controls. They have increased proliferation of B cells.|||Belongs to the TENT family.|||Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group and enhances mRNA stability and gene expression (PubMed:34048638). Can also elongate RNA oligos ending with uridine molecule, provided that the sequence is adenosine-rich (By similarity). Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein (PubMed:28931820).|||Cytoplasm|||Expressed by splenocytes, expression is increased in activated splenocytes.|||In splenocytes, expression is highly induced after yctivation by IL4 and LPS.|||Interacts with BCCIP and PABPC1; the interaction has no effect on TENT5C poly(A) polymerase function. Interacts with PLK4; this interaction leads to the TENT5C recruitment into the centrosome.|||Nucleus|||centrosome http://togogenome.org/gene/10090:Gstm2 ^@ http://purl.uniprot.org/uniprot/P15626 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Participates in the formation of novel hepoxilin regioisomers.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Repin1 ^@ http://purl.uniprot.org/uniprot/Q5U4E2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimers and homomultimers. Found in a complex with RIP60 and RIP100 (By similarity).|||Nucleus|||Sequence-specific double-stranded DNA-binding protein required for initiation of chromosomal DNA replication. Binds on 5'-ATT-3' reiterated sequences downstream of the origin of bidirectional replication (OBR) and a second, homologous ATT sequence of opposite orientation situated within the OBR zone. Facilitates DNA bending (By similarity). http://togogenome.org/gene/10090:Gm20826 ^@ http://purl.uniprot.org/uniprot/J3QK38 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Lsm6 ^@ http://purl.uniprot.org/uniprot/P62313|||http://purl.uniprot.org/uniprot/Q542U7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome. Component of the heptameric LSM1-LSM7 complex, which consists of LSM1, LSM2, LSM3, LSM4, LSM5, LSM6 and LSM7.|||Cytoplasm|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA. Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner, facilitating the efficient association of RNA processing factors with their substrates. Component of the cytoplasmic LSM1-LSM7 complex, which is thought to be involved in mRNA degradation by activating the decapping step in the 5'-to-3' mRNA decay pathway. http://togogenome.org/gene/10090:Gstm1 ^@ http://purl.uniprot.org/uniprot/P10649 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). Participates in the formation of novel hepoxilin regioisomers.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Camk1d ^@ http://purl.uniprot.org/uniprot/B1AW58|||http://purl.uniprot.org/uniprot/Q3TDM2|||http://purl.uniprot.org/uniprot/Q3UH04|||http://purl.uniprot.org/uniprot/Q8BW96 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-180 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-180 results in several fold increase in total activity. Unlike CaMK4, may be unable to exhibit autonomous activity after Ca(2+)/calmodulin activation (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta (By similarity). Isoform 1 but not isoform 2 activates CREB1.|||Cytoplasm|||Down-regulated upon cholesterol-rich diet.|||Expressed ubiquitously with high levels in brain and low levels in kidney. Isoform 2 is highly expressed in brain compared to other tissues. In hematopoietic cell lines predominant expression was detected in T and EC cells.|||In EML cell line differentiation, expression increases 4 to 8 hours after treatment with all-trans retinoic acid (ATRA) and then declines after 24 hours of ATRA induction.|||Inactive. Does not activate CREB1.|||Nucleus|||The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate. http://togogenome.org/gene/10090:Prdx6b ^@ http://purl.uniprot.org/uniprot/Q8BG37 ^@ Function|||Similarity ^@ Belongs to the peroxiredoxin family. Prx6 subfamily.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. http://togogenome.org/gene/10090:Pole4 ^@ http://purl.uniprot.org/uniprot/Q9CQ36 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Accessory component of the DNA polymerase epsilon complex (By similarity). Participates in DNA repair and in chromosomal DNA replication (By similarity).|||Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interaction with POLE3 is a prerequisite for further binding with POLE and POLE2.|||Nucleus http://togogenome.org/gene/10090:1700088E04Rik ^@ http://purl.uniprot.org/uniprot/Q9D9S1 ^@ Similarity ^@ Belongs to the UPF0193 (EVG1) family. http://togogenome.org/gene/10090:Serpinb6d ^@ http://purl.uniprot.org/uniprot/Q3UWK8 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Grem1 ^@ http://purl.uniprot.org/uniprot/O70326|||http://purl.uniprot.org/uniprot/Q3TNY7 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DAN family.|||Cytokine that may play an important role during carcinogenesis and metanephric kidney organogenesis, as BMP a antagonist required for early limb outgrowth and patterning in maintaining the FGF4-SHH feedback loop (PubMed:12808456, PubMed:15201225). Down-regulates the BMP4 signaling in a dose-dependent manner (PubMed:15133038). Antagonist of BMP2; inhibits BMP2-mediated differentiation of osteoblasts (in vitro) (By similarity). Acts as inhibitor of monocyte chemotaxis (By similarity).|||Highly expressed in spleen and to a lesser extent in lung, skeletal muscle and kidney. Expressed only in non-transformed cells or primary fibroblasts in culture but not in established transformed or tumor derived cell lines. Broadly expressed in limb bud mesenchyme but restricted to the distal limb bud mesenchyme and concentrated posteriorly. Expressed in ovary especially in granulosa cells of follicles of type 4.|||Homodimer; can also form homooligomers. Interacts with BMP2; can form higher oligomers with BMP2 (By similarity). Interacts with SLIT1 and SLIT2 in a glycosylation-dependent manner (By similarity).|||Secreted|||Up-regulated by GDF9 dose-dependent manner and BMP4 in granulosa cells. Highly regulated during folliculogenesis. http://togogenome.org/gene/10090:Xkr7 ^@ http://purl.uniprot.org/uniprot/Q5GH64 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the XK family.|||Cell membrane http://togogenome.org/gene/10090:Col4a6 ^@ http://purl.uniprot.org/uniprot/B1AVK5|||http://purl.uniprot.org/uniprot/Q9ESQ1 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.|||basement membrane http://togogenome.org/gene/10090:Gas6 ^@ http://purl.uniprot.org/uniprot/Q61592 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ GAS6 deficient mice show protection against thrombosis, but no spontaneous bleeding.|||Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.|||Heterodimer and heterotetramer with AXL.|||Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses.|||Secreted http://togogenome.org/gene/10090:Gm21443 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:D3Ertd751e ^@ http://purl.uniprot.org/uniprot/Q8BGN2 ^@ Similarity ^@ Belongs to the UPF0462 family. http://togogenome.org/gene/10090:Rprd2 ^@ http://purl.uniprot.org/uniprot/Q6NXI6 ^@ Subunit ^@ Associates with the RNA polymerase II complex. http://togogenome.org/gene/10090:Card19 ^@ http://purl.uniprot.org/uniprot/Q9D1I2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with BCL10 by CARD-CARD interaction.|||Endoplasmic reticulum membrane|||Mitochondrion membrane|||Plays a role in inhibiting the effects of BCL10-induced activation of NF-kappa-B. http://togogenome.org/gene/10090:Smco2 ^@ http://purl.uniprot.org/uniprot/Q9DA21 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tradd ^@ http://purl.uniprot.org/uniprot/B2RRZ7|||http://purl.uniprot.org/uniprot/Q3U0V2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Glycosylated at Arg-243 by S.typhimurium protein Ssek1: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions and assembly of the oligomeric TNFRSF1A/TNFR1 complex, thereby disrupting TNF signaling.|||Adapter molecule for TNFRSF1A/TNFR1 that specifically associates with the cytoplasmic domain of activated TNFRSF1A/TNFR1 mediating its interaction with FADD (By similarity). Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa-B (By similarity). The nuclear form acts as a tumor suppressor by preventing ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A by TRIP12: acts by interacting with TRIP12, leading to disrupt interaction between TRIP12 and isoform p19ARF/ARF of CDKN2A (PubMed:22561347).|||Cytoplasm|||Mice develop tumors. In a C57BL/6 genetic background, mice exhibit a shorter lifespan than wild-type, but exhibit low incidences of observable tumor formation. In the FVB/N background, which is more tumor-prone, mice show a significant increase in the spontaneous development of a broad range of tumor types.|||Nucleus|||Requires the intact death domain to associate with TNFRSF1A/TNFR1.|||Stimulation of TNF-alpha receptor TNFRSF1A leads to the formation of two distinct signaling complexes (PubMed:14585990). Plasma membrane-bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK-beta and IKBKG/IKK-gamma promoting cell survival (PubMed:14585990). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 promoting cell apoptosis (By similarity). Within complex I, interacts with TNFRSF1A/TNFR1, TRAF2 and kinase RIPK1 (By similarity). Within complex I, interacts with TRPC4AP; the interaction promotes NF-kappa B activation (PubMed:14585990). UXT1 associates with complex I; the interaction prevents the formation of complex II (By similarity). Within complex I Interacts with scaffold protein DAB2IP (By similarity). Interacts with autophagy receptor SQSTM1 (By similarity). Interacts with E3 ligase TRIP12 (PubMed:22561347). Interacts with kinase HIPK2 (By similarity). Interacts with keratin KRT14 (PubMed:16702408). Interacts with keratin KRT18 (By similarity). Interacts with KRT16 and KRT17 (PubMed:16702408). Interacts with FADD (PubMed:30185824). Interacts with TOMM70 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Loxl4 ^@ http://purl.uniprot.org/uniprot/E9Q600|||http://purl.uniprot.org/uniprot/Q8CEU1|||http://purl.uniprot.org/uniprot/Q924C6 ^@ Caution|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the lysyl oxidase family.|||Contains 1 lysine tyrosylquinone.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May modulate the formation of a collagenous extracellular matrix.|||Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).|||The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.|||extracellular space http://togogenome.org/gene/10090:Or1e30 ^@ http://purl.uniprot.org/uniprot/Q8VEZ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krt5 ^@ http://purl.uniprot.org/uniprot/Q32P04|||http://purl.uniprot.org/uniprot/Q922U2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Expressed in basal layer cells of the stratified squamous epithelia at 15.5 dpc (PubMed:29518391). Expressed in the skin after birth (PubMed:29518391). Expressed in ameloblasts at the cervical and apical mid-regions of mandibular molars at birth, abundance at the apical mid-region significantly increases at P1, and is maintained throughout enamel development until P9 when ameloblasts start losing their integrity (PubMed:12657653). Expressed in ameloblasts at the incisal region of mandibular molars at P3 (PubMed:12657653). Expressed at the Tomes' processes of ameloblasts at the incisal region at P5 (PubMed:12657653). Expression at the incisal region decreased at P7 and P9 (PubMed:12657653). Weakly expressed in the spinous and granular layers of the tongue at P20 (PubMed:32758484).|||Expressed in the corneal epithelium (at protein level) (PubMed:26758872, PubMed:11408584). Expressed in the epidermis of the ear (at protein level) (PubMed:24751727). Expressed in the basal and spinous layers of the skin at birth (at protein level) (PubMed:11408584).|||Heterodimer of a type I and a type II keratin. Heterodimer with type I keratin KRT25 leading to the formation of keratin intermediate filament (KIF) network (By similarity). Forms a heterodimer (via 2B domains) with KRT14 (via 2B domains) (PubMed:24940650). Interacts with PLEC isoform 1C, when in a heterodimer with KRT14 (PubMed:24940650). Interacts with TCHP (By similarity). Interacts with EPPK1 (PubMed:18285451). Interacts with AMELX (PubMed:12657653). Interacts with PKP1 (via N-terminus) and PKP2 (By similarity).|||O-glycosylated.|||Paws are frequently denuded and epidermis loses contact with the dermis following the mechanical stress of birth, mice die within 1 hour of birth (PubMed:11408584). Tongue cytolysis is evident following birth even before the first milk uptake (PubMed:11408584). Complete loss of keratin filaments in the basal layer, leading to cleavage of the epidermis in the subnuclear cytoplasm just superficial to the hemidesmosomes (PubMed:11408584). Increase in Krt6 expression in the spinous and lower granular layers as well as weakly in basal layer of the blistering roof of cytolyzing cells at birth (PubMed:11408584). Decrease in Krt14 expression in the skin following birth (PubMed:11408584). Increase in Langerhans cells in the epidermis (PubMed:19267394). Decrease in Ctnnd1/p120 localization to the plasma membrane and adherens junctions of basal keratinocytes (PubMed:19267394). Increase in the cytokines Cxcl16, Ccl2, Ccl19 and Ccl20 in the epidermis at birth (PubMed:19267394).|||Phosphorylated by CDK1, AURKB and Rho-kinase, phosphorylation is regulated by the cell cycle (PubMed:29518391). Thr-24 phosphorylation, mediated by CDK1, peaks during prometaphase or metaphase cells with phosphorylated filamentous structures evident throughout the cytoplasm during early mitosis (PubMed:29518391). CDK1 phosphorylates Thr-24 in mitotic cells at the site of injury (PubMed:29518391).|||Required for the formation of keratin intermediate filaments in the basal epidermis and maintenance of the skin barrier in response to mechanical stress (PubMed:11408584). Regulates the recruitment of Langerhans cells to the epidermis, potentially by modulation of the abundance of macrophage chemotactic cytokines, macrophage inflammatory cytokines and CTNND1 localization in keratinocytes (PubMed:19267394).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Emc4 ^@ http://purl.uniprot.org/uniprot/Q9CZX9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC4 family.|||Component of the ER membrane protein complex (EMC).|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Rpl31 ^@ http://purl.uniprot.org/uniprot/P62900|||http://purl.uniprot.org/uniprot/Q5M9K9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL31 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Cacfd1 ^@ http://purl.uniprot.org/uniprot/Q8BG21 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calcium channel flower family.|||Membrane http://togogenome.org/gene/10090:Pld3 ^@ http://purl.uniprot.org/uniprot/O35405 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (PubMed:30111894). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in collaboration with PLD4 (PubMed:30111894). May be important in myotube formation. Plays a role in lysosomal homeostasis. Involved in the regulation of endosomal protein sorting (By similarity).|||Belongs to the phospholipase D family.|||Deficient mice exhibit no altered phenotype except a exaggerated response of macrophages to TLR9 (PubMed:30111894). Morphology of PLD3-deficient brains does not reveal any major abnormalities but an altered lysosomal structure (PubMed:29386126). PDL3 and PLD4 double-deficient mice are unable to survive beyond the age of 21 days due to severe liver inflammation (PubMed:30111894). Livers from double-knockout mice develop lethal hepatic autoinflammatory disease that could be prevented by a single allele of either PDL3 or PLD4 (PubMed:30111894).|||Early endosome membrane|||Endoplasmic reticulum membrane|||Endosome membrane|||Expressed at higher level in brain than in non-nervous tissue. Expressed in mature neurons of the forebrain and appears to be turned on at late stages of neurogenesis. Expressed during late neuronal development in the forebrain (PubMed:9813063). Expressed in the pyramidal neurons of the cortex and hippocampus (PubMed:28128235). Low expression in the cerebellum (PubMed:30312375).|||Golgi apparatus membrane|||Interacts with APP.|||It was initially thought that PDL3 has phospholipase D activity due to its HKD motifs. The second HKD motif contains Glu instead of the canonical Asp. Its enzyme activity is therefore unsure. Catalytic phospholipase D activity is still controversial (PubMed:30312375, PubMed:9813063) (By similarity). Its closest homolog PLD4, exhibits no phospholipase activity (By similarity).|||Late endosome membrane|||Lysosome lumen|||N-glycosylated.|||Proteolytically processed to a soluble form that is stable within endosomes and lysosomes. During transport through the secretory pathway becomes proteolysed by cysteine proteases, thereby releasing a stable soluble lysosomal lumenal polypeptide, whereas the transmembrane-bound fragment is rapidly degraded. Its transport route to lysosomes involves ubiquitination and the ESCRT complex.|||Ubiquitinated. Ubiquitination mediates sorting into lysosomes.|||Up-regulated during myoblast differentiation into myotubes. http://togogenome.org/gene/10090:Cldn7 ^@ http://purl.uniprot.org/uniprot/Q9Z261 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the claudin family.|||Cell membrane|||Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3 (PubMed:10601346). The phosphorylated form interacts with EPCAM (By similarity).|||Expressed predominantly in lung and kidney.|||Phosphorylated.|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Tead2 ^@ http://purl.uniprot.org/uniprot/P48301|||http://purl.uniprot.org/uniprot/Q3UPV9|||http://purl.uniprot.org/uniprot/Q80UL2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highest expression in brain. High levels also found in lung, testis and ovarian follicle cells. Lower levels in heart and spleen.|||In the embryo, levels fall after fertilization until the 2-4 cell stage and then increase rapidly.|||Interacts with YAP1 and WWTR1/TAZ.|||Nucleus|||Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction (By similarity). Binds to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3'). May be involved in the gene regulation of neural development. Binds to the M-CAT motif. http://togogenome.org/gene/10090:Spats2l ^@ http://purl.uniprot.org/uniprot/E9PVQ3|||http://purl.uniprot.org/uniprot/Q91WJ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATS2 family.|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Gm10670 ^@ http://purl.uniprot.org/uniprot/K7N6B7 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Tekt2 ^@ http://purl.uniprot.org/uniprot/Q922G7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tektin family.|||Expressed in the testes (at protein level).|||Localized in the flagella of elongating spermatids from developmental step 15 to maturity.|||May interact with CCDC172 (PubMed:24394471). Interacts with TEKT3 (By similarity).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme (PubMed:15340058). Plays a key role in the assembly or attachment of the inner dynein arm to microtubules in sperm flagella and tracheal cilia (PubMed:15340058). Forms filamentous polymers in the walls of ciliary and flagellar microtubules (PubMed:15340058).|||Tyrosine phosphorylated.|||cilium axoneme|||flagellum axoneme|||microtubule organizing center http://togogenome.org/gene/10090:Uqcrc1 ^@ http://purl.uniprot.org/uniprot/Q9CZ13 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-138 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the peptidase M16 family. UQCRC1/QCR1 subfamily.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783). Interacts with UQCC6 (PubMed:32161263). Interacts with STMP1 (PubMed:35101990).|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties. May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (By similarity). Seems to play an important role in the maintenance of proper mitochondrial function in nigral dopaminergic neurons (By similarity).|||Expressed in neurons and astrocytes of the cerebral cortex and hippocampus (at protein level).|||Mitochondrion inner membrane|||Results in early embryonic lethality. http://togogenome.org/gene/10090:Spa17 ^@ http://purl.uniprot.org/uniprot/Q545M2|||http://purl.uniprot.org/uniprot/Q62252 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer. May interact with ROPN1 (By similarity).|||Membrane|||Sperm surface zona pellucida binding protein. Helps to bind spermatozoa to the zona pellucida with high affinity. Might function in binding zona pellucida and carbohydrates (By similarity).|||Sperm surface zona pellucida binding protein. Helps to bind spermatozoa to the zona pellucida with high affinity. Might function in binding zona pellucida and carbohydrates.|||Testis- and sperm-specific. http://togogenome.org/gene/10090:Or13a25 ^@ http://purl.uniprot.org/uniprot/Q8VGL9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trem2 ^@ http://purl.uniprot.org/uniprot/Q99NH8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in the brain, specifically in microglia (at protein level) (PubMed:15728241, PubMed:28802038, PubMed:28855301, PubMed:28077724, PubMed:28592261, PubMed:29794134, PubMed:29752066, PubMed:27477018, PubMed:28559417). Expressed in macrophages (at protein level) (PubMed:11241283, PubMed:28802038, PubMed:28559417). Expressed at higher levels in the CNS, heart and lung than in lymph nodes or in other non-lymphoid tissues such as kidney, liver and testis (PubMed:12472885). In the CNS not all microglia express TREM2 (PubMed:12472885). Brain regions with an incomplete blood-brain barrier had the lowest percentages of TREM2 expressing microglia, whereas the lateral entorhinal and cingulate cortex had the highest percentages (PubMed:12472885).|||Expression is increased during oxygen-glucose deprivation, reaching the highest expression level 12 hours after reoxygenation. Expression is also increased by ischemia, where maximum expression is reached 7 days after ischemic conditions.|||Forms a receptor signaling complex with TYROBP which mediates signaling and cell activation following ligand binding (PubMed:11241283). Acts as a receptor for amyloid-beta protein 42, a cleavage product of the amyloid-beta precursor protein APP, and mediates its uptake and degradation by microglia (PubMed:27477018, PubMed:29518356). Binding to amyloid-beta 42 mediates microglial activation, proliferation, migration, apoptosis and expression of pro-inflammatory cytokines, such as IL6R and CCL3, and the anti-inflammatory cytokine ARG1 (PubMed:27477018, PubMed:29518356). Acts as a receptor for lipoprotein particles such as LDL, VLDL, and HDL and for apolipoproteins such as APOA1, APOA2, APOB, APOE, APOE2, APOE3, APOE4, and CLU and enhances their uptake in microglia (PubMed:27477018). Binds phospholipids (preferably anionic lipids) such as phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol and sphingomyelin (By similarity). Regulates microglial proliferation by acting as an upstream regulator of the Wnt/beta-catenin signaling cascade (PubMed:28077724). Required for microglial phagocytosis of apoptotic neurons (PubMed:24990881). Also required for microglial activation and phagocytosis of myelin debris after neuronal injury and of neuronal synapses during synapse elimination in the developing brain (PubMed:15728241, PubMed:28592261, PubMed:29752066, PubMed:25631124). Regulates microglial chemotaxis and process outgrowth, and also the microglial response to oxidative stress and lipopolysaccharide (PubMed:30232263, PubMed:29663649, PubMed:28483841, PubMed:29859094). It suppresses PI3K and NF-kappa-B signaling in response to lipopolysaccharide; thus promoting phagocytosis, suppressing pro-inflammatory cytokine and nitric oxide production, inhibiting apoptosis and increasing expression of IL10 and TGFB (PubMed:29663649). During oxidative stress, it promotes anti-apoptotic NF-kappa-B signaling and ERK signaling (PubMed:28592261). Plays a role in microglial MTOR activation and metabolism (PubMed:28802038). Regulates age-related changes in microglial numbers (PubMed:30548312, PubMed:29752066, PubMed:25631124). Triggers activation of the immune responses in macrophages and dendritic cells (By similarity). Mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (PubMed:18957693). In dendritic cells, it mediates up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (By similarity). Involved in the positive regulation of osteoclast differentiation (PubMed:16418779).|||Mice exhibit a strong increase in self-grooming behavior, defective social behavior, and some sensorimotor defects (PubMed:25631124, PubMed:29752066). Aged mice show decreases in age-related neuronal loss and increases in synaptic density in the substantia nigra and the hippocampus (PubMed:30548312). They also exhibit a decrease in the connectivity between the retrosplenial cortices, subiculum, hippocampus and anterior cingulate, as a result of defective synaptic growth thus impairing their function (PubMed:29752066).|||Monomer (By similarity). After ectodomain shedding, the extracellular domain oligomerizes, which is enhanced and stabilized by binding of phosphatidylserine (By similarity). Interacts with TYROBP/DAP12 (PubMed:11241283, PubMed:29518356). Interaction with TYROBP is required for stabilization of the TREM2 C-terminal fragment (TREM2-CTF) which is produced by proteolytic processing (By similarity).|||Secreted|||Undergoes ectodomain shedding through proteolytic cleavage by ADAM10 and ADAM17 to produce a transmembrane segment, the TREM2 C-terminal fragment (TREM2-CTF), which is subsequently cleaved by gamma-secretase. http://togogenome.org/gene/10090:Zfp787 ^@ http://purl.uniprot.org/uniprot/Q8BIF9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Grb10 ^@ http://purl.uniprot.org/uniprot/Q60760 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. A similar role in the mediation of ubiquitination has also been suggested with INSR. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2.|||At 13.5 dpc, expressed in most embryonic tissues and in placenta. At 14.5 dpc, expressed at high levels in a variety of muscle tissues, including that of the face and trunk, the intercostal muscles, the diaphragm and cardiac muscle, the tongue and limbs (at protein level). In the brain, most abundant expression in the subependymal layers, in the meninges and in the choroid plexus (both epithelium and mesenchyme) (at protein level). High levels in the liver, bronchioles and the cartilage of the atlas, ribs and long bones (at protein level). In the kidney, expression limited to the developing tubules and mesenchyme (at protein level). Also detected in the adrenal gland and pancreatic bud (at protein level). At 12.5 dpc, paternal allele expression detected in the cartilage of the limbs, ribs and face and in the meninges. At 14.5 dpc, paternal allele expressed in the cartilage of the axis, ribs, head, and long bones, in the heart, lungs, gut, umbilicus and tongue, as well as in the meninges of the fourth ventricle. Not detected in the skeletal muscle. In most tissues, paternal expression is lower than maternal.|||Belongs to the GRB7/10/14 family.|||Cytoplasm|||Disruption of the maternal allele results in overgrowth of both the embryo and placenta such that mutant mice are at birth about 30% larger than normal. This effect occurs during embryogenesis and results in addition in disproportionate overgrowth of the liver with relative sparing of the brain. The major part of the growth phenotype seems to be IGF2-independent.|||Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain. Poorly binds to the EGFR. Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex (By similarity). Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15. When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6. Binds to activated NRAS (By similarity).|||Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation.|||Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling.|||Predominant isoform in most tissues.|||The GRB10 locus is imprinted. The maternal allele is expressed in most tissues, except the brain where it is expressed from the paternal allele. Expression from the maternal allele in fetal and adult brain was however described in PubMed:10861285.|||The PH domain binds relatively non-specifically to several phosphoinositides, including PI(5)P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities.|||Widely expressed. http://togogenome.org/gene/10090:Pramel17 ^@ http://purl.uniprot.org/uniprot/Q3UTC0 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Rcc2 ^@ http://purl.uniprot.org/uniprot/Q8BK67 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Chromosome|||Induced by TP53/p53 in response to oxidative stress and DNA damage.|||Interacts with RAC1 (PubMed:25074804). Interacts with nucleotide-free and with GDP and GTP-bound forms of RAC1, with a slight preference for GDP-bound RAC1. Binds preferentially to the nucleotide-free form of RAC1. Interacts with CORO1C. Interacts with microtubules (By similarity).|||Midbody|||Multifunctional protein that may affect its functions by regulating the activity of small GTPases, such as RAC1 and RALA. Required for normal progress through the cell cycle, both during interphase and during mitosis. Required for the presence of normal levels of MAD2L1, AURKB and BIRC5 on inner centromeres during mitosis, and for normal attachment of kinetochores to mitotic spindles. Required for normal organization of the microtubule cytoskeleton in interphase cells. Functions as guanine nucleotide exchange factor (GEF) for RALA. Interferes with the activation of RAC1 by guanine nucleotide exchange factors (By similarity). Prevents accumulation of active, GTP-bound RAC1, and suppresses RAC1-mediated reorganization of the actin cytoskeleton and formation of membrane protrusions (PubMed:25074804). Required for normal cellular responses to contacts with the extracellular matrix of adjacent cells, and for directional cell migration in response to a fibronectin gradient (in vitro) (By similarity).|||Nucleus|||centromere|||cytoskeleton|||nucleolus|||spindle http://togogenome.org/gene/10090:Gtse1 ^@ http://purl.uniprot.org/uniprot/Q8R080 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation ^@ By p53 when exposed to different DNA damaging agents, including gamma irradiation and chemotherapeutic drugs.|||Expression begins at S phase, accumulates in late S/G2 phase and disappears in G1 phase.|||May be involved in p53-induced cell cycle arrest in G2/M phase by interfering with microtubule rearrangements that are required to enter mitosis. Overexpression delays G2/M phase progression.|||Phosphorylated in mitosis.|||cytoskeleton http://togogenome.org/gene/10090:Or12d13 ^@ http://purl.uniprot.org/uniprot/Q920Y8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Efr3a ^@ http://purl.uniprot.org/uniprot/Q8BG67 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EFR3 family.|||Cell membrane|||Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, EFR3A probably acts as the membrane-anchoring component. Also involved in responsiveness to G-protein-coupled receptors; it is however unclear whether this role is direct or indirect.|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2).|||Expression is reduced in animals with impaired hearing.|||Palmitoylated at its N-terminus, anchoring the protein to the plasma membrane.|||Widely expressed (PubMed:25380825). Expressed in neurons of the superior olivary complex of the auditory brainstem. Also expressed at lower levels in the cochlear nucleus, the lateral leminiscal nuclei and the inferior collicus (PubMed:15363888).|||cytosol http://togogenome.org/gene/10090:Sap18 ^@ http://purl.uniprot.org/uniprot/E9Q317|||http://purl.uniprot.org/uniprot/O55128|||http://purl.uniprot.org/uniprot/Q4FZH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAP18 family.|||Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit mRNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits the formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function (By similarity).|||Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit mRNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits the formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function.|||Cytoplasm|||Expressed in all tissues tested; highest levels in the brain, kidney and muscle; lowest levels in lung spleen, liver, intestine and testis, and moderate levels in salivary gland and heart.|||Found in a mRNA splicing-dependent exon junction complex (EJC). Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) and PSAP complexes consisting of RNPS1, SAP18 and either ACIN1 or PNN, respectively; the ASAP and PSAP complexes probably are formed mutually exclusive. For the ASAP complex, the association of SAP18 seems to require a preformed RNPS1:ACIN1 complex. Forms a complex with SIN3A and HDAC1. Interacts with SUFU.|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Cntnap3 ^@ http://purl.uniprot.org/uniprot/E9PY62 ^@ Caution|||Similarity ^@ Belongs to the neurexin family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Or2c1 ^@ http://purl.uniprot.org/uniprot/P23275 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Olfactory epithelium. Present in various subcellular compartments of the olfactory sensory neurons, particularly in the axonal processes and neve terminals.|||Olfactory receptor that is activated by the binding of organosulfur odorants with thioether groups such as (methylthio)methanetiol (MTMT) (PubMed:29659735). Also binds odorants acetophenone and benzaldehyde (PubMed:25901328). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (Probable). May be involved in the molecular processes underlying fasciculation and targeting of olfactory axons (PubMed:15342743). http://togogenome.org/gene/10090:Nle1 ^@ http://purl.uniprot.org/uniprot/Q3URT5|||http://purl.uniprot.org/uniprot/Q8VEJ4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Embryonic lethality prior to 6.5 dpc with death of inner mass cells. Embryos implant but die shortly after.|||Expression detected in the embryo at 7.0 dpc, 11.0 dpc and 15.0 dpc and also in the adult.|||Highest expression in heart, brain, lung, liver, skeletal muscle and testis with lower levels in spleen and kidney.|||Plays a role in regulating Notch activity (Probable). Plays a role in regulating the expression of CDKN1A and several members of the Wnt pathway, probably via its effects on Notch activity. Required during embryogenesis for inner mass cell survival.|||nucleolus http://togogenome.org/gene/10090:Ampd3 ^@ http://purl.uniprot.org/uniprot/O08739 ^@ Cofactor|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ AMP deaminase plays a critical role in energy metabolism.|||Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.|||Binds 1 zinc ion per subunit.|||Found in heart, lung brain, spleen, kidney and to a lesser extent in liver.|||Homotetramer. http://togogenome.org/gene/10090:Smc1a ^@ http://purl.uniprot.org/uniprot/Q9CU62 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMC family. SMC1 subfamily.|||Chromosome|||Forms a heterodimer with SMC3 in cohesin complexes. Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their SMC hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21. In germ cell cohesin complexes, SMC1A is mutually exclusive with SMC1B (PubMed:10375619). Interacts with STAG3 (PubMed:11483963). Found in a complex with CDCA5, SMC3 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN. Found in a complex containing POLE and SMC3. Interacts with BRCA1, SYCP2, NDC80, RPGR and BRAT1. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (By similarity).|||Involved in chromosome cohesion during cell cycle and in DNA repair. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, and works as a downstream effector in the ATM/NBS1 branch of S-phase checkpoint (By similarity). Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint.|||Nucleus|||Phosphorylated upon ionizing radiation or DNA methylation. Phosphorylation of Ser-957 and Ser-966 activates it and is required for S-phase checkpoint activation (By similarity).|||The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity).|||Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation.|||Ubiquitous (at protein level).|||centromere http://togogenome.org/gene/10090:Klhdc3 ^@ http://purl.uniprot.org/uniprot/Q8VEM9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter KLHDC3.|||Cytoplasm|||Expressed specifically in testis, particularly in pachytene spermatocytes.|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC3) complex specifically recognizes proteins with a glycine (Gly) at the C-terminus, leading to their ubiquitination and degradation: recognizes the C-terminal -Arg-(Xaa)n-Arg-Gly, -Arg-(Xaa)n-Lys-Gly, and -Arg-(Xaa)n-Gln-Gly degrons. The CRL2(KLHDC3) complex mediates ubiquitination and degradation of truncated SELENOV and SEPHS2 selenoproteins produced by failed UGA/Sec decoding, which end with a glycine (By similarity). May be involved in meiotic recombination process (PubMed:12606021). http://togogenome.org/gene/10090:Rasgrp4 ^@ http://purl.uniprot.org/uniprot/Q8BTM9 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RASGRP family.|||Cell membrane|||Cytoplasm|||Due to an intron retention.|||Expressed at all stages in the development of mast cells.|||Expressed by mast cells and their progenitors (at protein level).|||Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. May function in mast cells differentiation.|||Minor isoform which is not activated by DAG and probably not functional. Preferentially expressed in the C3H/HeJ strain. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||The phorbol-ester/DAG-type zinc finger mediates the binding and the functional activation by DAG. http://togogenome.org/gene/10090:Gfod1 ^@ http://purl.uniprot.org/uniprot/Q3UHD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Gfo/Idh/MocA family.|||Secreted http://togogenome.org/gene/10090:Ndufaf5 ^@ http://purl.uniprot.org/uniprot/A2APY7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Arginine hydroxylase involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early stages. Acts by mediating hydroxylation of 'Arg-111' of NDUFS7. May also have methyltransferase activity.|||Belongs to the methyltransferase superfamily.|||Interacts with NDUFAF8, leading to stabilize NDUFAF5. Interacts with NDUFS7. Interacts with PYURF (via TRM112 domain); the interaction is direct and stabilizes NDUFAF5 protein (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Crispld2 ^@ http://purl.uniprot.org/uniprot/Q8BZQ2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to heparin, dermatan sulfate and chondroitin sulfate.|||Expressed in the developing oropharynx and nasopharynx at 13.5 dpc, in the mandible at 14.5 dpc and in the cartilage primordia of the nasal bones, palate and tooth germs at 17.5 dpc. Detected in the embryonic liver at 13.5, 14.5 and 17.5 dpc.|||Present in kidney renal tubules (at protein level).|||Promotes matrix assembly.|||Secreted http://togogenome.org/gene/10090:Mettl17 ^@ http://purl.uniprot.org/uniprot/Q3U2U7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. Rsm22 family.|||Interacts with mitochondrial small ribosomal subunit (mt-SSU) subunits MRPS15 and MRPS27.|||Mitochondrion matrix|||Probable S-adenosyl-L-methionine-dependent RNA methyltransferase required to stabilize the mitochondrial small ribosomal subunit (mt-SSU) (PubMed:31487196). Required for protein translation in mitochondria (PubMed:31487196). http://togogenome.org/gene/10090:Prss56 ^@ http://purl.uniprot.org/uniprot/F2YMG0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Endoplasmic reticulum membrane|||Expressed in the eye: present in the retina and in the optic nerve.|||First detected in the eye at 17 dpc and maintained into adulthood.|||Mice display the glaucoma-relevant mutant 4 (Grm4) phenotype, with angle-closure glaucoma and eyes having short axial length. High intraocular pressure (IOP) in mutant eyes increases with age and the anterior chambers become enlarged in some eyes at around 3 months of age. Eye's angles are not occluded with abnormal tissue (synechia) and have detectable trabecular meshwork and Schlemm's canal (2 important drainage structures). However, compromised aqueous humor drainage (outflow) contributes to the IOP elevation. After IOP elevation, mutants develop glaucomatous neurodegeneration, which is characterized by retinal ganglion cell death and optic nerve atrophy.|||Serine protease required during eye development. http://togogenome.org/gene/10090:Yipf4 ^@ http://purl.uniprot.org/uniprot/Q8C407 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the YIP1 family.|||Interacts with YIPF3 and YIPF5.|||Involved in the maintenance of the Golgi structure.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Rrp1 ^@ http://purl.uniprot.org/uniprot/P56183 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRP1 family.|||Embryonic, expression starting between days 1 and 10.|||Interacts with C1QBP. Interacts with RRP1B.|||Plays a critical role in the generation of 28S rRNA.|||nucleolus http://togogenome.org/gene/10090:Ark2c ^@ http://purl.uniprot.org/uniprot/E9QAU8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Around 10% of mice die at birth. While surviving pups are the same size as their littermates at birth, they fail to thrive and grow, reaching only 50% of the size of their siblings at postnatal day 15. They die before weaning during the first 3 postnatal weeks. Null pups display relaxed forepaws and reduced dorsiflexion. Hind limb defects are also observed. Defects are caused by inefficient growth of motor axons to distant muscles.|||Belongs to the Arkadia family.|||Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer.|||E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation (PubMed:23610558). Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP (PubMed:23610558). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL (PubMed:23610558).|||Expressed in neurons of the nervous system.|||Monomer; binding to the ubiquitin-conjugating enzyme E2 does not trigger homodimerization.|||Nucleus|||The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin. Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer. http://togogenome.org/gene/10090:Grid2 ^@ http://purl.uniprot.org/uniprot/Q61625 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRID2 subfamily.|||Cell membrane|||Defects in Grid2 are the cause of the Lurcher phenotype. Heterozygous animals display a characteristic swaying of the hind quarters and jerky up and down movements following cerebellar Purkinje cell degeneration during postnatal development. Homozygous animals die shortly after birth because of a massive loss of midbrain and hindbrain neurons during late embryogenesis.|||Expressed selectively in cerebellar Purkinje cells where it is localized in dendritic spines.|||Postsynaptic cell membrane|||Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. Promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses through the beta-NRX1-CBLN1-GRID2 triad complex.|||Tetramer; dimer of dimers (By similarity). Interacts with EML2, MAGI2 (via PDZ domains) and AP4M1 (By similarity). Interacts with BECN1, GOPC, GRID2IP, SHANK1 and SHANK2 (PubMed:12372286, PubMed:15207857, PubMed:17027646). Interacts with CBLN2, but not with CBLN4 (PubMed:22220752). Interacts with CBLN1 (via C1q domain); the interaction is CBLN1-NRX1 complex formation-dependent; CBLN1-binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal domain dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:20395510, PubMed:21410790, PubMed:22220752, PubMed:29782851).|||The PDZ-binding motif mediates interaction with GOPC. http://togogenome.org/gene/10090:Or1o11 ^@ http://purl.uniprot.org/uniprot/Q8VFA1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Snrpn ^@ http://purl.uniprot.org/uniprot/P63163|||http://purl.uniprot.org/uniprot/Q3UN87 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the snRNP SmB/SmN family.|||Encoded on a bicistronic transcript that code for two proteins, SNRPN and SNURF.|||Expressed in brain and embryonic stem (ES) cells.|||Interacts with TDRD3.|||May be involved in tissue-specific alternative RNA processing events.|||Nucleus http://togogenome.org/gene/10090:Cby1 ^@ http://purl.uniprot.org/uniprot/Q9D1C2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Chibby' is Japanese for 'small'; the gene was so named for the RNAi phenotype seen in flies.|||Belongs to the chibby family.|||Found in heart, brain, lung, liver, muscle, kidney and testis. Levels are approximately 3-fold higher in embryonic and adult heart than in lung or liver.|||Golgi apparatus|||Homodimer. Interacts with polycystin-2/PKD2 and GM130. Interacts with the C-terminal region of CTNNB1. Interacts (C-terminus) with TCIM (C-terminus), TCIM competes with CTNNB1 for the interaction with CBY1. Interacts with FAM92A; this interaction facilitates targeting of FAM92A to cilium basal body. Interacts with CIBAR2.|||Inhibits the Wnt/Wingless pathway by binding to CTNNB1/beta-catenin and inhibiting beta-catenin-mediated transcriptional activation through competition with TCF/LEF transcription factors. Has also been shown to play a role in regulating the intracellular trafficking of polycystin-2/PKD2 and possibly of other intracellular proteins. Promotes adipocyte and cardiomyocyte differentiation.|||Nucleus speckle|||Ubiquitously expressed in early stages of embryonic stem cell differentiation but decreases at later stages when high expression is restricted to cardiomyocytes.|||centriole|||cilium basal body|||trans-Golgi network http://togogenome.org/gene/10090:Rmnd5a ^@ http://purl.uniprot.org/uniprot/Q80YQ8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. Catalytic activity of the complex is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1.|||Cytoplasm|||Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles.|||nucleoplasm http://togogenome.org/gene/10090:Cep85l ^@ http://purl.uniprot.org/uniprot/A0A1W2P884 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CEP85 family.|||Knockdown of the expression into neural stem cells of the mouse neocortex causes a neuronal migration defect.|||Plays an essential role in neuronal cell migration.|||centrosome http://togogenome.org/gene/10090:Pkd1 ^@ http://purl.uniprot.org/uniprot/O08852 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After synthesis, undergoes autoproteolytic cleavage between Leu-3040 and Thr-3041 in the GPS domain (PubMed:25405894). Cleavage at the GPS domain occurs through a cis-autoproteolytic mechanism involving an ester-intermediate via N-O acyl rearrangement (By similarity). This process takes place in the early secretory pathway, depends on initial N-glycosylation, and requires the REJ domain (By similarity). PKD1 is ubiquitously and incompletely cleaved in wild-type mice, so that uncleaved and cleaved PKD1 molecules coexist. The differential patterns of cleavage during embryonic development, as well as in adult mice, suggest different functions of uncleaved and cleaved molecules (PubMed:18003909).|||Belongs to the polycystin family.|||Cell membrane|||Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. Both PKD1 and PKD2 are required for channel activity (By similarity). Involved in renal tubulogenesis (PubMed:24939912). Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:12514735). Acts as a regulator of cilium length, together with PKD2 (PubMed:20096584). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling. May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate.|||Endoplasmic reticulum|||Golgi apparatus|||Interacts with PKD2; the interaction is required for ciliary localization (PubMed:25405894). Component of a heterotetrameric channel complex with PKD2; the tetramer contains one PKD1 chain and three PKD2 chains (By similarity). Interacts with PKD2L1 (PubMed:15548533). Interacts with PRKX; involved in differentiation and controlled morphogenesis of the kidney. Interacts (via extracellular domain) with WNT3A, WNT4 and WNT9B (By similarity). Interacts with WNT5A, DVL1 and DVL2 (PubMed:27214281). Interacts with NPHP1 (via SH3 domain) (PubMed:20856870). Interacts with BBS1, BBS4, BBS5 and TTC8. Interacts with RGS7 (By similarity). Interacts (via C-terminal domain) with RABEP1; the interaction connects PKD1:PKD2 to GGA1 and ARL3 that mediate the ciliary targeting (PubMed:25405894).|||Knockin mice expressing non-cleavable PKD1 show a hypomorphic phenotype. They are viable, show rapid cystic dilation in renal collecting duct and distal convoluted tubule, but not in the proximal portion of the nephron, during the postnatal period, and die with severe uremia, mostly at 3 weeks of age. Additionally, they show dilation of the common bile duct and intrahepatic biliary ducts, but develop a normal pancreas within their life span.|||The LDL-receptor class A domain is atypical; the potential calcium-binding site is missing.|||cilium http://togogenome.org/gene/10090:Uprt ^@ http://purl.uniprot.org/uniprot/B1AVZ0 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UPRTase family.|||Cytoplasm|||Nucleus|||The uracil binding region known from UPRTases is missing. http://togogenome.org/gene/10090:Klra4 ^@ http://purl.uniprot.org/uniprot/Q542S4|||http://purl.uniprot.org/uniprot/Q60651 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Homodimer; disulfide-linked. Interacts with the adapter protein TYROBP/DAP12; the interaction leads to natural killer cell activation (PubMed:9647200).|||Membrane|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Or5b94 ^@ http://purl.uniprot.org/uniprot/Q0VEV7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or9g4 ^@ http://purl.uniprot.org/uniprot/A2ALD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ktn1 ^@ http://purl.uniprot.org/uniprot/Q61595 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the kinectin family.|||Endoplasmic reticulum membrane|||Expressed in all tissues examined including 12-day embryo, adult heart, brain, ovary, kidney, lung, small intestine, spleen, thymus and pancreas.|||Isoform 6, isoform 7 and isoform 8 are detected in embryonic hippocampus but not in later developmental stages. Isoform 14, isoform 15 and isoform 16 are adult-specific.|||Receptor for kinesin thus involved in kinesin-driven vesicle motility. Accumulates in integrin-based adhesion complexes (IAC) upon integrin aggregation by fibronectin (By similarity). http://togogenome.org/gene/10090:Psmb3 ^@ http://purl.uniprot.org/uniprot/Q545G0|||http://purl.uniprot.org/uniprot/Q9R1P1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1B family.|||Component of the proteasome complex.|||Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.|||Cytoplasm|||Detected in liver (at protein level).|||Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. http://togogenome.org/gene/10090:Dffa ^@ http://purl.uniprot.org/uniprot/O54786 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Caspase-3 cleaves DFF45 at 2 sites to generate an active factor.|||Cytoplasm|||Heterodimer of DFFA and DFFB.|||Inhibitor of the caspase-activated DNase (DFF40). http://togogenome.org/gene/10090:Cdx2 ^@ http://purl.uniprot.org/uniprot/P43241|||http://purl.uniprot.org/uniprot/Q543L9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Caudal homeobox family.|||Can bind DNA as a monomer or homodimer.|||In the intestine, detected in ileum and proximal and distal colon (at protein level) (PubMed:16027724). In adult small intestine, predominantly localized in crypt and lower villus cells of the epithelium (at protein level) (PubMed:11729123). Expressed in the intestine but not detected in other tissues including stomach, liver, kidney, spleen, brain, heart, lung, pancreas, skeletal muscle and testis (PubMed:7935448). Expressed specifically in gut epithelium where it is not restricted to a particular cell lineage. Abundant expression is seen in the proximal colon with slightly lower levels in distal colon (PubMed:7910823, PubMed:1671571). Expression in the proximal colon is not restricted either to a particular cell lineage or stage of differentiation while in the distal colon it is more abundant in the differentiated cells towards the top of the crypt.|||Nucleus|||Phosphorylation at Ser-60 reduces transactivation capacity (PubMed:11729123). Phosphorylation at Ser-281 reduces transactivation capacity and increases ubiquitin-dependent proteasome degradation (PubMed:16027724).|||Transcription factor which regulates the transcription of multiple genes expressed in the intestinal epithelium (PubMed:9933478, PubMed:16027724). Binds to the promoter of the intestinal sucrase-isomaltase SI and activates SI transcription (PubMed:7935448). Binds to the DNA sequence 5'-ATAAAAACTTAT-3' in the promoter region of VDR and activates VDR transcription (PubMed:9933478). Binds to and activates transcription of LPH (By similarity). Activates transcription of CLDN2 and intestinal mucin MUC2 (PubMed:16027724). Binds to the 5'-AATTTTTTACAACACCT-3' DNA sequence in the promoter region of CA1 and activates CA1 transcription (PubMed:9512360). Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Binds preferentially to methylated DNA (By similarity).|||Ubiquitinated, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Hfe ^@ http://purl.uniprot.org/uniprot/P70387|||http://purl.uniprot.org/uniprot/Q5SZ87 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Binds TFR through the extracellular domain in a pH-dependent manner.|||Binds to transferrin receptor (TFR) and reduces its affinity for iron-loaded transferrin.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd34 ^@ http://purl.uniprot.org/uniprot/Q543B6|||http://purl.uniprot.org/uniprot/Q543Y2|||http://purl.uniprot.org/uniprot/Q64314 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CD34 family.|||Expressed in the kidney where it is detected in the thin limb of Henle's loop (at protein level) (PubMed:31605441). Highly expressed in hematopoietic progenitor cell lines, brain and testis, and moderately in the thymus, spleen, and bone marrow, but not in adult liver (PubMed:1709048).|||Highly glycosylated.|||Membrane|||Phosphorylated on serine residues by PKC.|||Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. Presents carbohydrate ligands to selectins (By similarity). http://togogenome.org/gene/10090:Galm ^@ http://purl.uniprot.org/uniprot/Q8K157 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldose epimerase family.|||Cytoplasm|||Monomer.|||Mutarotase that catalyzes the interconversion of beta-D-galactose and alpha-D-galactose during galactose metabolism. Beta-D-galactose is metabolized in the liver into glucose 1-phosphate, the primary metabolic fuel, by the action of four enzymes that constitute the Leloir pathway: GALM, GALK1 (galactokinase), GALT (galactose-1-phosphate uridylyltransferase) and GALE (UDP-galactose-4'-epimerase). Involved in the maintenance of the equilibrium between the beta- and alpha-anomers of galactose, therefore ensuring a sufficient supply of the alpha-anomer for GALK1. Also active on D-glucose although shows a preference for galactose over glucose. http://togogenome.org/gene/10090:Pof1b ^@ http://purl.uniprot.org/uniprot/Q8K4L4 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in ovary between 16.5 dpc and P5.|||Expression absent in adult ovary.|||Interacts with nonmuscle actin.|||It is uncertain whether Met-1 or Met-2 is the initiator. The first methionine is not conserved among other organisms, but rat. It could be rodent-specific.|||Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development (By similarity).|||tight junction http://togogenome.org/gene/10090:Ptafr ^@ http://purl.uniprot.org/uniprot/Q62035 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By lipopolysaccharide (LPS).|||Cell membrane|||Found in a range of organs. Expressed most strongly in spleen, followed by skeletal muscle, lung and small intestine. Expressed at moderate levels in the heart. Expressed at relatively low levels in the brain, liver and kidney.|||Interacts with ARRB1.|||Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G protein that activates a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Eogt ^@ http://purl.uniprot.org/uniprot/Q8BYW9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 61 family.|||Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in extracellular proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Specifically glycosylates the Thr residue located between the fifth and sixth conserved cysteines of folded EGF-like domains.|||Endoplasmic reticulum lumen|||Expressed at embryonic day (E) 10.5 in the growing edge of the limb buds. At 11.5 dpc, enriched in the apical ectodermal ridge of the limbs. By 12.5 dpc, expression assumes a digit-condensation pattern in the 4 limbs.|||Widely expressed. Expressed in brain, heart, kidney, lung, skeletal muscles and thymus. Highest expression is observed in lung and the lowest in skeletal muscles. http://togogenome.org/gene/10090:Tnpo1 ^@ http://purl.uniprot.org/uniprot/Q8BFY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the importin beta family. Importin beta-2 subfamily.|||Cytoplasm|||Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates (PubMed:11493596). May mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Involved in nuclear import of M9-containing proteins. In vitro, binds directly to the M9 region of the heterogeneous nuclear ribonucleoproteins (hnRNP), A1 and A2 and mediates their nuclear import. Involved in hnRNP A1/A2 nuclear export. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (By similarity). In vitro, mediates nuclear import of SRP19 (By similarity). Mediates the import of histones H2A, H2B, H3 and H4 (PubMed:11493596). Mediates nuclear import of ADAR/ADAR1 in a RanGTP-dependent manner (By similarity).|||Identified in a complex that contains TNPO1, RAN and RANBP1 (By similarity). Binds HNRPA1, HNRPA2, HNRNPDL, RPS7, RPL5 and RAN. Interacts with H2A, H2B, H3 and H4 histones (PubMed:11493596). Interacts with isoform 1 and isoform 5 of ADAR/ADAR1 (via DRBM 3 domain). Interacts with SNAI1 (via zinc fingers); the interaction mediates SNAI1 nuclear import. Interacts with SNAI2 (via zinc fingers) (By similarity). Interacts with RPL23A (via BIB domain) and SRP19; this interaction is involved in RPL23A and SRP19 import into the nucleus (By similarity).|||Nucleus http://togogenome.org/gene/10090:Rsph14 ^@ http://purl.uniprot.org/uniprot/Q9D3W1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the flagellar radial spoke RSP14 family.|||Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB.|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.|||flagellum axoneme http://togogenome.org/gene/10090:Mkrn3 ^@ http://purl.uniprot.org/uniprot/Q60764 ^@ Developmental Stage|||Function|||Miscellaneous|||Tissue Specificity ^@ E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.|||Expressed at the blastocyst stage and the embryonic days 8-17, as well as in undifferentiated and differentiated embryonic stem cells. Expressed in the arcuate nucleus of both male and female animals. Levels of expression are highest on postnatal days 10 and 12, begin to decline on day 15, and reaches a nadir by days 18 to 22, at which time expression is 10 to 20% of the levels detected at 10 days. The timing of the decline in protein expression correlated with the ages at which arcuate KISS1 and TAC2 have been shown to increase, heralding the onset of puberty.|||Expressed in testis, brain, heart and kidney. Ubiquitously detected at low levels throughout the entire embryo, but expression is highest in the ventricular layers of the brain.|||Imprinted, expressed from the paternal chromosome only. The maternal methylation is established promptly after fertilization prior to syngamy. http://togogenome.org/gene/10090:Samd5 ^@ http://purl.uniprot.org/uniprot/Q3V1H9 ^@ Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in kidney glomeruli, and in peribiliary gland (PBG) cells at the hepatic hilum (at protein level). Detected in liver, kidney and small intestine.|||Interacts promiscuously (via SAM domain) with EPHA5, EPHA6, EPHA7, EPHA8, EPHB1, EPHB2, EPHB3 and EPHB4 (via SAM domain) (in vitro).|||Strongly induced in EPCAM-positive liver cells in response to liver damage caused by long-term 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) feeding. http://togogenome.org/gene/10090:Zfp672 ^@ http://purl.uniprot.org/uniprot/Q99LH4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Ceacam16 ^@ http://purl.uniprot.org/uniprot/E9QA28 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in cochleae from embryonic day 17 to postnatal day 42.|||Belongs to the immunoglobulin superfamily. CEA family.|||Expressed in cochlear outer hair cells (OHC).|||Homooligomer; can for homodimers and homotetramers (By similarity). Interacts with TECTA and TECTB (PubMed:25080593).|||Mutant mice show loss of striated-sheet matrix and Hensen's stripe, a prominent feature in the basal two-thirds of the tectorial membrane. They have enhanced spontaneous, stimulus-frequency, and transiently evoked otoacoustic emissions.|||Required for proper hearing, plays a role in maintaining the integrity of the tectorial membrane.|||Secreted http://togogenome.org/gene/10090:Vmn1r119 ^@ http://purl.uniprot.org/uniprot/E9Q4H3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ltbp4 ^@ http://purl.uniprot.org/uniprot/Q3UGU1|||http://purl.uniprot.org/uniprot/Q8K4G1 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LTBP family.|||Contains hydroxylated asparagine residues.|||Forms part of the large latent transforming growth factor beta precursor complex; removal is essential for activation of complex. Interacts with LTBP1 and TGFB1. Interacts with EFEMP2; this interaction promotes fibrillar deposition of EFEMP2 (PubMed:25713297).|||Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice reveal significant disruption of elastic fibers in multiple tissues. They develop pulmonary septation defects, rectal prolapse, colorectal adenomas, and dilated cardiomyopathy. They survive up to six months (mid-adult age) without major clinical symptoms.|||Sequence incomplete.|||extracellular matrix http://togogenome.org/gene/10090:Or1o3 ^@ http://purl.uniprot.org/uniprot/Q8VFD9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4k51 ^@ http://purl.uniprot.org/uniprot/Q8VGE7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chodl ^@ http://purl.uniprot.org/uniprot/Q9CXM0 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During gestation (7dpc to 15 dpc) its expression is up-regulated. In 15 dpc embryo is expressed in muscle cells of heterogeneous origin, including those from tongue, trunk, and tail. In newborn mice localized to limb striated muscle cells. Expressed in myoblasts undergoing myogenic differentiation during proliferation and differentiation phases (PubMed:12711387). Expressed in spinal chord motor neurons at 10.5 dpc. Detected in the plexus region of the developing limb bud at 10.5 dpc and 11.5 dpc (PubMed:20437528).|||In adult mice preferentially expressed in skeletal muscle, testis, brain, and lung. Expressed in striated muscle (at protein level). Expressed in spinal chord. Detected in spinal chord fast motor neurons (at protein level).|||Interacts with RABGGTB (PubMed:18161010).|||Isoform 1 but not isoform 2 expression is down-regulated at postnatal day (P) 7 in spinal muscular atrophy (SMA) model motor neurons before onset of disease.|||May play a role in the development of the nervous system such as in neurite outgrowth and elongation (PubMed:24067532). May be involved in motor axon growth and guidance (By similarity).|||Membrane http://togogenome.org/gene/10090:Itga8 ^@ http://purl.uniprot.org/uniprot/A2ARA8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin alpha chain family.|||Cell membrane|||Expressed in mesenchymal cells of developing organs such as gut, lung, gonads and nephrogenic cord.|||Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-8 associates with beta-1.|||In brain, expressed in deep cortex, hippocampal CA1, basolateral amygdala and striatum. In kidney, expressed in glomerular mesengium (at protein level).|||Integrin alpha-8/beta-1 functions in the genesis of kidney and probably of other organs by regulating the recruitment of mesenchymal cells into epithelial structures. It recognizes the sequence R-G-D in a wide array of ligands including TNC, FN1, SPP1 TGFB1, TGFB3 and VTN. NPNT is probably its functional ligand in kidney genesis. Neuronal receptor for TNC it mediates cell-cell interactions and regulates neurite outgrowth of sensory and motor neurons.|||Membrane|||Mice display renal agenesis and dysgenesis. This is associated with a reduced expression of Gdnf that is similarly found in mice lacking Npnt. Adult mice also display increased susceptibility to glomerular capillary destruction upon mechanical stress. Mice lacking Itga8 also have difficulty balancing associated with structural defects in the inner ear where utricular hair cells lack stereocilia. http://togogenome.org/gene/10090:Il1rapl1 ^@ http://purl.uniprot.org/uniprot/B1ASU0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the interleukin-1 receptor family.|||axon|||dendrite http://togogenome.org/gene/10090:Cyb5r3 ^@ http://purl.uniprot.org/uniprot/Q9DCN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||Catalyzes the reduction of two molecules of cytochrome b5 using NADH as the electron donor.|||Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MTARC2 (By similarity). Interacts with MTLN; the interaction is required to maintain cellular lipid composition and leads to stimulation of mitochondrial respiratory complex I activity (PubMed:31296841).|||Endoplasmic reticulum membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Hnrnpd ^@ http://purl.uniprot.org/uniprot/G3X9W0|||http://purl.uniprot.org/uniprot/G5E8G0|||http://purl.uniprot.org/uniprot/Q60668 ^@ Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Arg-345 is dimethylated, probably to asymmetric dimethylarginine.|||Binds with high affinity to RNA molecules that contain AU-rich elements (AREs) found within the 3'-UTR of many proto-oncogenes and cytokine mRNAs. Also binds to double- and single-stranded DNA sequences in a specific manner and functions a transcription factor. Each of the RNA-binding domains specifically can bind solely to a single-stranded non-monotonous 5'-UUAG-3' sequence and also weaker to the single-stranded 5'-TTAGGG-3' telomeric DNA repeat. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats. Binding of RRM1 to DNA inhibits the formation of DNA quadruplex structure which may play a role in telomere elongation. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. May play a role in the regulation of the rhythmic expression of circadian clock core genes. Directly binds to the 3'UTR of CRY1 mRNA and induces CRY1 rhythmic translation. May also be involved in the regulation of PER2 translation.|||Contaminating sequence.|||Cytoplasm|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR and SYNCRIP. Interacts with IGF2BP2. Interacts with GTPBP1. Interacts with EIF4G1; the interaction requires RNA. Interacts with EIF3B and RPS3.|||Methylated by PRMT1, in an insulin-dependent manner. The PRMT1-mediated methylation regulates its phosphorylation (By similarity).|||Nucleus http://togogenome.org/gene/10090:Wnt4 ^@ http://purl.uniprot.org/uniprot/P22724|||http://purl.uniprot.org/uniprot/Q3ZB23 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Wnt family.|||Detected along the length of the mesonephros at 9.5 to 10.5 dpc. At 11.0 dpc, detected in the mesenchyme of the gonads in both sexes and in mesonephros. At 11.5 dpc, sex-specific differentiation of the gonads begins, and Wnt4 is down-regulated in male gonads, but not in female gonads. Detected in mesenchyme cells underlying the newly formed Mullerian duct in females, but not in the Wolffian duct in males (PubMed:9989404). During kidney development, detected at 11.5 dpc in condensed mesenchymal cells on both sides of the stalk of the ureter. Detected on pretubular aggregates upon initiation of ureteric bud branching at 12.5 dpc. Detected on primitive tubular aggregates at 13.5 dpc. Detected on comma-shaped and S-shaped bodies by 14.5 dpc, and is restricted to kidney cortex by 16.5 dpc (PubMed:7990960).|||In adults in lung and brain.|||Interacts with PORCN (PubMed:10866835). Interacts with PKD1 (By similarity).|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Plays an important role in the embryonic development of the urogenital tract and the lung (PubMed:7990960, PubMed:9989404, PubMed:16054034, PubMed:17537789, PubMed:19830824, PubMed:26321050). Required for normal mesenchyme to epithelium transition during embryonic kidney development (PubMed:7990960, PubMed:16054034, PubMed:17537789, PubMed:19830824). Required for the formation of early epithelial renal vesicles during kidney development (PubMed:16054034). Required for normal formation of the Mullerian duct in females, and normal levels of oocytes in the ovaries (PubMed:9989404, PubMed:19830824). Required for normal down-regulation of 3 beta-hydroxysteroid dehydrogenase in the ovary (PubMed:9989404). Required for normal lung development and for normal patterning of trachael cartilage rings (PubMed:26321050).|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Mutant embryos show normal early stages of kidney development, but later stages of kidney development are disrupted (PubMed:7990960, PubMed:19830824). Mutant embryos develop to term, but the pups die within 24 hours after birth, probably due to the absence of functional kidneys (PubMed:7990960). Reproductive organs in newborn males appear normal (PubMed:9989404). External genitalia from newborn females appear normal, but they lack a Mullerian duct and their gonads and sex ducts appear masculinized (PubMed:9989404, PubMed:19830824). Their ovaries contain less than 10% of the normal number of oocytes, and these are in the process of degenerating (PubMed:9989404). Mutant embryos display altered patterning of tracheal cartilage rings. By 13.5 dpc the size of their lungs is significantly reduced, and at 17.5 dpc the left lung lobe is on average 35% smaller than for wild-type (PubMed:26321050).|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||extracellular matrix http://togogenome.org/gene/10090:Orc2 ^@ http://purl.uniprot.org/uniprot/Q543F8|||http://purl.uniprot.org/uniprot/Q59IX1|||http://purl.uniprot.org/uniprot/Q60862 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORC2 family.|||Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase (By similarity). Interacts with DBF4 (PubMed:12614612). Interacts with MCM10. Interacts with LRWD1 throughout the cell cycle; this interaction, wich occurs only with non-ubiquitinated form of LRWD1, prevents LRWD1 ubiquitination and hence stabilizes the protein. Interacts with POLQ (By similarity).|||Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.|||Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (By similarity). Binds histone H3 and H4 trimethylation marks H3K9me3, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3 (By similarity).|||Component of the origin recognition complex (ORC).|||Nucleus http://togogenome.org/gene/10090:Slc45a1 ^@ http://purl.uniprot.org/uniprot/Q8BIV7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycoside-pentoside-hexuronide (GPH) cation symporter transporter (TC 2.A.2) family.|||Membrane|||Proton-associated glucose transporter in the brain. http://togogenome.org/gene/10090:Erh ^@ http://purl.uniprot.org/uniprot/G3UW85|||http://purl.uniprot.org/uniprot/P84089|||http://purl.uniprot.org/uniprot/Q4FZH7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E(R) family.|||Homodimer (PubMed:15937287). Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, PRMT1 and ERH. Interacts with CHTOP (By similarity).|||May have a role in the cell cycle.|||Nucleus http://togogenome.org/gene/10090:Vmn2r116 ^@ http://purl.uniprot.org/uniprot/E9Q6I0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Expressed in the vomeronasal organ.|||No response of neurons in the vomeronasal organ or accessory olfactory bulb to Esp1 and no enhancement of lordosis following exposure to Esp1.|||Receptor for the Esp1 pheromone. Mediates the response to Esp1 which enhances female sexual receptive behavior (lordosis) upon male mounting, resulting in successful copulation. http://togogenome.org/gene/10090:Sbsn ^@ http://purl.uniprot.org/uniprot/Q8CIT9 ^@ Developmental Stage|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in epidermis, in suprabasal keratinocytes. Detected in suprabasal layers of embryonic epidermis and in stratified layers of embryonic tongue and palate. Detected in adult stomach.|||First detected after 15 days of embryonic development, and highly expressed after 17 days, coinciding with stratification of epidermis.|||Secreted|||Up-regulated in differentiating keratinocytes. http://togogenome.org/gene/10090:Tepsin ^@ http://purl.uniprot.org/uniprot/Q3U3N6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network.|||Cytoplasmic vesicle|||Interacts with AP4B1 and AP4E1; the interaction is direct and mediates the association of TEPSIN with the adapter-like complex 4 (AP-4), a heterotetramer composed of AP4B1, AP4E1, AP4M1 and AP4S1.|||cytosol|||trans-Golgi network membrane http://togogenome.org/gene/10090:Trdmt1 ^@ http://purl.uniprot.org/uniprot/O55055|||http://purl.uniprot.org/uniprot/Q5I0V6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.|||Cytoplasm|||Highly expressed in thymus, testis, and at much lower levels in spleen, lung, brain, heart, kidney, liver, skeletal muscle and embryonic stem cells.|||Mice are viable and fertile, but show loss of 5-methylcytidine(38) in tRNA (PubMed:21183079, PubMed:22885326). Mice lacking both Nsun2 and Trdmt1 display a complete loss of cytosine-C5 tRNA methylation, leading to development defects and impaired cellular differentiation causing lethality before P3 (PubMed:22885326).|||Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp). http://togogenome.org/gene/10090:Upk3a ^@ http://purl.uniprot.org/uniprot/Q9JKX8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the uroplakin-3 family.|||Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells. It also contributes to the formation of urothelial glycocalyx which may play an important role in preventing bacterial adherence (By similarity).|||Endoplasmic reticulum membrane|||Heterodimer with uroplakin-1B (UPK1B). http://togogenome.org/gene/10090:Casp1 ^@ http://purl.uniprot.org/uniprot/P29452 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C14A family.|||Cell membrane|||Cytoplasm|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit (PubMed:32109412). May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and NLRP2 and whose function would be the activation of pro-inflammatory caspases (By similarity). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287). Both the p10 and p20 subunits interact with MEFV (By similarity). Interacts with CARD17P/INCA and CARD18 (By similarity). Interacts with SERPINB1; this interaction regulates CASP1 activity (By similarity).|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-1 subunit p20) and a 10 kDa (Caspase-1 subunit p10) subunit.|||High level expression seen in spleen and lung, low level expression seen in brain, heart, liver, kidney, testis and skeletal muscle.|||Mutants are resitant to vaccinia virus (VACV) but not vesicular somatitis virus (VSV) infection. They show lower viral loads in the lungs compared to wild type mice, they produce higher levels of type I IFN, IL6 and RSAD2/Viperin after VCAV INFECTION.|||The two subunits are derived from the precursor sequence by an autocatalytic mechanism.|||Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:21147462, PubMed:32109412). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:21147462). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:21147462). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:32109412). In contrast to cleavage of interleukins IL1B and IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:18667412, PubMed:22464733, PubMed:35705808). Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590). In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (By similarity).|||Ubiquitinated via 'Lys-11'-linked polyubiquitination. Deubiquitinated by USP8. http://togogenome.org/gene/10090:Aadacl3 ^@ http://purl.uniprot.org/uniprot/A2A7Z8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the 'GDXG' lipolytic enzyme family.|||Membrane http://togogenome.org/gene/10090:Gk5 ^@ http://purl.uniprot.org/uniprot/Q8BX05 ^@ Similarity ^@ Belongs to the FGGY kinase family. http://togogenome.org/gene/10090:Hecw1 ^@ http://purl.uniprot.org/uniprot/Q8K4P8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1.|||Interacts with DVL1 and SSR3.|||Predominantly expressed in neurons of the spinal cord. http://togogenome.org/gene/10090:Crabp1 ^@ http://purl.uniprot.org/uniprot/P62965 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors.|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. http://togogenome.org/gene/10090:Catsperb ^@ http://purl.uniprot.org/uniprot/A2RTF1 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation (PubMed:34225353, PubMed:17478420). Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization (PubMed:17478420).|||CatSperb is absent in sperm from mice lacking CatSper1, suggesting that stable expression of CatSperb protein requires CatSper1.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:21224844, PubMed:17478420, PubMed:19516020, PubMed:34998468). HSPA1 may be an additional auxiliary complex member (PubMed:17478420, PubMed:19516020). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (PubMed:34998468).|||Testis-specific. Specifically present in the principal piece of sperm tail (at protein level). Specifically expressed in the seminiferous tubules but not in the interstitial cells. Within the tubules, it is expressed in spermatocytes and spermatids, but not in spermatogonia.|||flagellum membrane http://togogenome.org/gene/10090:Gpr27 ^@ http://purl.uniprot.org/uniprot/O54897 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. Possible candidate for amine-like G-protein coupled receptor (By similarity). http://togogenome.org/gene/10090:Rgs9bp ^@ http://purl.uniprot.org/uniprot/Q148R9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RGS7BP/RGS9BP family.|||Membrane|||Mice show light responses that recover at a abnormally slow rate.|||Predominantly expressed in photoreceptors of the retina. Weakly expressed in other areas of the central nervous system.|||Regulator of G protein-coupled receptor (GPCR) signaling in phototransduction. Participates in the recovery phase of visual transduction via its interaction with RGS9-1 isoform. Acts as a membrane-anchor that mediates the targeting of RGS9-1 to the photoreceptor outer segment, where phototransduction takes place. Enhances the ability of RGS9-1 to stimulate G protein GTPase activity, allowing the visual signal to be terminated on the physiologically time scale. It also controls the proteolytic stability of RGS9-1, probably by protecting it from degradation.|||Specifically interacts with isoform RGS9-1 of RGS9. Interaction is decreased when RGS9-1 is phosphorylated at 'Ser-475'. Component of the RGS9-1-Gbeta5 complex composed of RGS9-1, Gbeta5 (GNB5) and RGS9BP. http://togogenome.org/gene/10090:Zfp553 ^@ http://purl.uniprot.org/uniprot/Q3US17 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Eme2 ^@ http://purl.uniprot.org/uniprot/Q56A04 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EME1/MMS4 family.|||Interacts with MUS81 to form a DNA structure-specific endonuclease which cleaves substrates such as 3'-flap structures.|||Interacts with MUS81.|||Nucleus http://togogenome.org/gene/10090:AW554918 ^@ http://purl.uniprot.org/uniprot/Q6NZK5 ^@ Function|||Subunit ^@ Competes with SMC1 for binding to SMC3. May affect the availability of SMC3 to engage in the formation of multimeric protein complexes.|||Interacts (via N- and C-terminal domains) with SMC3 (via central hinge region). http://togogenome.org/gene/10090:Bzw1 ^@ http://purl.uniprot.org/uniprot/Q9CQC6 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the BZW family.|||Broadly expressed, with highest levels in testis.|||Translation initiation regulator which represses repeat-associated non-AUG (RAN) initiated translation probably by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (By similarity). Enhances histone H4 gene transcription but does not seem to bind DNA directly (By similarity). http://togogenome.org/gene/10090:Mall ^@ http://purl.uniprot.org/uniprot/Q91X49 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MAL family.|||Membrane http://togogenome.org/gene/10090:Gsg1l2 ^@ http://purl.uniprot.org/uniprot/M0QWL6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the GSG1 family.|||Membrane http://togogenome.org/gene/10090:Acsl4 ^@ http://purl.uniprot.org/uniprot/Q8BW44|||http://purl.uniprot.org/uniprot/Q91YN3|||http://purl.uniprot.org/uniprot/Q9QUJ7 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in steroidogenic tissues, also found in the kidney, brain and liver.|||Belongs to the ATP-dependent AMP-binding enzyme family.|||Both triacsin C and rosiglitazone inhibit arachidonoyl-CoA ligase activity.|||Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially activates arachidonate and eicosapentaenoate as substrates. Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (By similarity).|||Cell membrane|||Endoplasmic reticulum membrane|||Induced by adrenocorticotropic hormone (ACTH) and suppressed by glucocorticoid.|||Microsome membrane|||Mitochondrion outer membrane|||Peroxisome membrane http://togogenome.org/gene/10090:Nme4 ^@ http://purl.uniprot.org/uniprot/Q9WV84 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NDK family.|||Expressed in the base region of the oxyntic and pyloric mucosae.|||Homohexamer (By similarity). Interacts with OPA1 (By similarity). Interacts with CAPN8 (PubMed:16476741).|||Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Through the catalyzed exchange of gamma-phosphate between di- and triphosphonucleosides participates in regulation of intracellular nucleotide homeostasis. Binds to anionic phospholipids, predominantly to cardiolipin; the binding inhibits its phosphotransfer activity. Acts as mitochondria-specific NDK; its association with cardiolipin-containing mitochondrial inner membrane is coupled to respiration suggesting that ADP locally regenerated in the mitochondrion innermembrane space by its activity is directly taken up via ANT ADP/ATP translocase into the matrix space to stimulate respiratory ATP regeneration. Proposed to increase GTP-loading on dynamin-related GTPase OPA1 in mitochondria. In vitro can induce liposome cross-linking suggesting that it can cross-link inner and outer membranes to form contact sites, and promotes intermembrane migration of anionic phosphoplipids. Promotes the redistribution of cardiolipin between the mitochondrial inner membrane and outer membrane which is implicated in pro-apoptotic signaling (By similarity).|||Mitochondrion intermembrane space|||Mitochondrion matrix http://togogenome.org/gene/10090:Uggt2 ^@ http://purl.uniprot.org/uniprot/E9Q4X2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 8 family.|||Endoplasmic reticulum lumen http://togogenome.org/gene/10090:Kcnj16 ^@ http://purl.uniprot.org/uniprot/Q9Z307 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the proximal and distal segments of the nephron.|||Basolateral cell membrane|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ16 subfamily.|||Heterodimer with Kir4.1/KCNJ10; this interaction is required for KCNJ16 localization to the basolateral membrane in kidney cells. As a heterodimer with KCNJ10, may interact with MAGI1; this interaction may facilitate KCNJ10/KCNJ16 potassium channel expression at the basolateral membrane in kidney cells. May form heterodimers with Kir2.1/KCNJ2.|||Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ16 may be involved in the regulation of fluid and pH balance. In the kidney, together with KCNJ10, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules.|||Membrane http://togogenome.org/gene/10090:Ddx10 ^@ http://purl.uniprot.org/uniprot/Q80Y44 ^@ Domain|||Function|||Similarity ^@ Belongs to the DEAD box helicase family. DDX10/DBP4 subfamily.|||Putative ATP-dependent RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis. http://togogenome.org/gene/10090:Or52r1b ^@ http://purl.uniprot.org/uniprot/Q8VGV9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Taf1d ^@ http://purl.uniprot.org/uniprot/Q9D4V4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Interacts with UBTF (By similarity).|||Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ust ^@ http://purl.uniprot.org/uniprot/Q3TRA2|||http://purl.uniprot.org/uniprot/Q8BUB6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 3 family.|||Golgi apparatus membrane|||Membrane|||Sulfotransferase that catalyzes the transfer of sulfate to the position 2 of uronyl residues. Has mainly activity toward iduronyl residues in dermatan sulfate, and weaker activity toward glucuronyl residues of chondroitin sulfate. Has no activity toward desulfated N-resulfated heparin (By similarity). http://togogenome.org/gene/10090:Slitrk4 ^@ http://purl.uniprot.org/uniprot/Q810B8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLITRK family.|||Cell membrane|||In the adult, significant expression is detected only in the brain. Broadly expressed in embryonic brain with highest expression in subventricular zone, subplate, cortical plate, pyramidal cell layer of hippocampus, thalamus and hypothalamus.|||In the embryo, expressed from day 10-12 and continues through later gestational development and into adulthood.|||Interacts (via LRR 1 and 2 repeats) with PTPRD (via extracellular domain).|||It is involved in synaptogenesis and promotes synapse differentiation (By similarity). Suppresses neurite outgrowth (PubMed:14550773).|||Membrane http://togogenome.org/gene/10090:Pdxdc1 ^@ http://purl.uniprot.org/uniprot/Q99K01 ^@ Similarity ^@ Belongs to the group II decarboxylase family. http://togogenome.org/gene/10090:Psma6 ^@ http://purl.uniprot.org/uniprot/E0CXB1|||http://purl.uniprot.org/uniprot/Q9QUM9 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Interacts with ALKBH4 (By similarity).|||Up-regulated in liver tumor tissues (at protein level). http://togogenome.org/gene/10090:Gm21310 ^@ http://purl.uniprot.org/uniprot/J3QQ23 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Dsg1c ^@ http://purl.uniprot.org/uniprot/Q7TSF0 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.|||Cytoplasm|||Expressed in embryo at 17 dpc.|||Expressed in epidermis, brain, liver, skeletal, muscle and testis.|||Nucleus|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Anxa8 ^@ http://purl.uniprot.org/uniprot/O35640|||http://purl.uniprot.org/uniprot/Q921D0 ^@ Domain|||Function|||Similarity ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. http://togogenome.org/gene/10090:Ubtd2 ^@ http://purl.uniprot.org/uniprot/Q6PGH0 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Stag2 ^@ http://purl.uniprot.org/uniprot/A2AFF6|||http://purl.uniprot.org/uniprot/O35638|||http://purl.uniprot.org/uniprot/Q3TG33 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCC3 family.|||Chromosome|||Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate.|||Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis (By similarity).|||Interacts directly with RAD21 in cohesin complex. Cohesin complexes are composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein (STAG1, STAG2 or STAG3). In cohesin complexes, STAG2 is mutually exclusive with STAG1 and STAG3 (By similarity).|||Nucleus|||Part of the cohesin complex which is composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein.|||Phosphorylated by PLK1. The large dissociation of cohesin from chromosome arms during prophase is partly due to its phosphorylation (By similarity).|||centromere http://togogenome.org/gene/10090:Csmd1 ^@ http://purl.uniprot.org/uniprot/Q5DTU1|||http://purl.uniprot.org/uniprot/Q923L3 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CSMD family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Fut4 ^@ http://purl.uniprot.org/uniprot/Q11127|||http://purl.uniprot.org/uniprot/Q544B8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 10 family.|||Catalyzes alpha(1->3) linkage of fucosyl moiety transferred from GDP-beta-L-fucose to N-acetyl glucosamine (GlcNAc) within type 2 lactosamine (LacNAc, Gal-beta(1->4)GlcNAc) glycan attached to N- or O-linked glycoproteins (PubMed:11485743). Robustly fucosylates nonsialylated distal LacNAc unit of the polylactosamine chain to form Lewis X antigen (CD15), a glycan determinant known to mediate important cellular functions in development and immunity. Fucosylates with lower efficiency sialylated LacNAc acceptors to form sialyl Lewis X and 6-sulfo sialyl Lewis X determinants that serve as recognition epitopes for C-type lectins (PubMed:11485743). Together with FUT7 contributes to SELE, SELL and SELP selectin ligand biosynthesis and selectin-dependent lymphocyte homing, leukocyte migration and blood leukocyte homeostasis (PubMed:11485743). In a cell type specific manner, may also fucosylate the internal LacNAc unit of the polylactosamine chain to form VIM-2 antigen that serves as recognition epitope for SELE (By similarity).|||Golgi stack membrane|||Highest expression in stomach and colon. It is also expressed in the lung, testis, uterus, small intestine and to a lesser extent in spleen, and ovary. Present in trace amounts in brain, thymus, heart, smooth muscle, kidney and bone marrow. Not found in liver, salivary gland and pancreas.|||Membrane|||Mice are born at the expected Mendelian rate. No visible phenotype; likely due to the redundancy with FUT7. Simultaneous knockdown of FUT4 and FUT7 results in leukocytosis characterized by an 18.4 fold increase in blood neutrophils and significant increases in blood monocytes, eosinophils, and lymphocytes numbers. http://togogenome.org/gene/10090:Slamf6 ^@ http://purl.uniprot.org/uniprot/Q9ET39 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed on hematopoietic cells. Isoform 3 is expressed in thymocytes and B lymphocytes of C57Bl/6 strain.|||Found in Slamf-haplotype 1 mice such as C557Bl/6 but not in Slamf-haplotype 2 strains including 129, Balb/c and NOD.|||Homodimer. Interacts with PTN6 and, upon phosphorylation, with PTN11 and SH2D1A/SAP (By similarity).|||Isoform 3 ameliorates spontaneous development in a systemic lupus erythematosus transfer model.|||Phosphorylated.|||Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2 (PubMed:19648922). Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (By similarity). Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (By similarity). In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (PubMed:18031695). Promotes T cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (By similarity). Promotes recruitment of RORC to the IL-17 promoter (By similarity). In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response (PubMed:25926831). In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP (PubMed:22683125). However, reported to mediated T-cell adhesion, to participate in stable T-cell:B-cell interactions and to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (PubMed:20153220, PubMed:25801429). Involved in regulation of autoimmunity. Isoform 3 may be suppressor of pathogenic T-cell proliferation (PubMed:21422172).|||The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). http://togogenome.org/gene/10090:Ogg1 ^@ http://purl.uniprot.org/uniprot/O08760|||http://purl.uniprot.org/uniprot/Q3UIL3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type-1 OGG1 family.|||DNA repair enzyme that incises DNA at 8-oxoG residues. Excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damaged DNA. Has a beta-lyase activity that nicks DNA 3' to the lesion.|||Highest expression in testis.|||Nucleus matrix|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Adgrg7 ^@ http://purl.uniprot.org/uniprot/Q8BM96 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Deficient mice exhibit less body weight gain and an increase in intestinal contraction frequency.|||Membrane|||Orphan receptor.|||Selectively expressed in the intestinal tissues. http://togogenome.org/gene/10090:Slfn2 ^@ http://purl.uniprot.org/uniprot/Q9Z0I6 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Schlafen family.|||Conditional deletion in T-cells leads to impaired T cell-mediated immunity (PubMed:33986151). T-cell show an accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation (PubMed:33986151).|||Cytoplasm|||Mainly expressed in the thymus, lymph node and spleen.|||Upon interferon-alpha (IFN-alpha) treatment.|||tRNA-binding protein involved in T-cell mediated immunity (PubMed:33986151). Plays a key role during the metabolic reprograming phase of activated T-cell, when T-cells produce reactive oxygen species (ROS): acts by binding tRNAs and protecting them from cleavage by the oxidative stress-activated ribonuclease angiogenin (ANG) (PubMed:33986151). Also required for T-cell quiescence maintenance (PubMed:20190759). http://togogenome.org/gene/10090:Angptl3 ^@ http://purl.uniprot.org/uniprot/Q9R182 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12671033). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (PubMed:26305978). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity; the function seems to be specific for the feeding conditions. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12909640, PubMed:16081640, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids; the cleaved N-terminal domain is more efficient than the uncleaved proprotein (PubMed:17681148). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (By similarity). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (PubMed:26305978). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR (PubMed:25954050). May stimulate hypothalamic LPL activity (PubMed:25338813).|||Down-regulated by insulin and leptin. Not regulated by nutritional status (fed/fasting) Up-regulated in podocytes by puromycin. Up-regulated after feeding in the hypothalamus.|||In part proteolytically cleaved by proprotein convertases; proposed to be involved in activation. In primary hepatocytes is intracellularily predominantly processed by FURIN and extracellularily by FURIN and PCSK6/PACE4. In 18.5 dpc embryos 75% of protein is found to be processed compared to 25 % in adults.|||Interacts with ANGPTL8 (By similarity). Interacts with ITGB3.|||Involved in angiogenesis (PubMed:11877390). Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration (By similarity). May increase the motility of podocytes. Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling (By similarity). May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation (PubMed:20633534, PubMed:24294595, PubMed:25710887). Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (PubMed:20959605).|||Low plasma levels of triglyceride, HDL cholesterol and HDL phospholipids, and non-esterified fatty acids (NEFA). Animals fed on high-fat, high-calorie (HFC) diet show reduced epididymal adipose tissue weight with no difference in adipocyte size. Hypotriglyceridemia with elevated postheparin plasma LPL activity is specifically observed in the fed state. Mice deficient in both Angptl3 and Angptl4 show an additive effect on plasma triglycerides and did not survive past 2 months of age.|||Predominantly expressed in liver, weakly expressed in kidney and lung. Expressed in podocytes (at protein level). Expressed in hypothalamic neurons (at protein level). Expressed in bone marrow sinusoidal endothelial cells (at protein level).|||Secreted|||The fibrinogen C-terminal domain is sufficient to mediate endothelial cell adhesion.|||Was suggested to inhibit LPL through a direct mechanism; however, the necessary concentrations to achieve the in vitro inhibition are at least 30-fold higher than ANGPTL3 plasma concentrations.|||lamellipodium http://togogenome.org/gene/10090:Sh2d4a ^@ http://purl.uniprot.org/uniprot/Q9D7V1 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||In the kidney, expressed only in the glomerulus. Expressed in T-cells, B-cells, macrophages and dendritic cells (at protein level). In adult, highest levels are found in muscle and lung with lower levels in kidney.|||Inhibits estrogen-induced cell proliferation by competing with PLCG for binding to ESR1, blocking the effect of estrogen on PLCG and repressing estrogen-induced proliferation (By similarity). May play a role in T-cell development and function.|||Interacts with ESR1.|||Upon CD3/CD28 stimulation in CD4 T-cells. http://togogenome.org/gene/10090:Timp4 ^@ http://purl.uniprot.org/uniprot/Q3USH7|||http://purl.uniprot.org/uniprot/Q9JHB3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protease inhibitor I35 (TIMP) family.|||Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.|||Expressed in brain, heart, ovary and skeletal muscle.|||Secreted http://togogenome.org/gene/10090:Vdac1 ^@ http://purl.uniprot.org/uniprot/Q60932 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic mitochondrial porin family.|||Cell membrane|||Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands. The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity.|||Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (By similarity). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:10716730, PubMed:15477379, PubMed:18988731). May mediate ATP export from cells (By similarity).|||High levels of expression detected in heart, kidney, brain, and skeletal muscle. Not expressed in testis.|||Homodimer and homotrimer; in response to cyclic AMP or calcium (By similarity). Interacts with hexokinases including HK1. The HK1-VDAC1 complex interacts with ATF2. Interacts with BCL2L1. Interacts with BAK1. Interacts with RTL10/BOP (via BH3 domain) (By similarity). Interacts with amyloid-beta and APP; induces VDAC1 dephosphorylation (PubMed:25168729). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF. Interacts with SPG7, NIPSNAP2 and SLC25A30 (By similarity). Interacts with TMEM41B (By similarity). Interacts with BCAP31 (By similarity).|||Inhibited by nitric oxide.|||Membrane raft|||Mitochondrion outer membrane|||Phosphorylation at Ser-206 by NEK1 promotes the open conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury. Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.|||Ubiquitinated (PubMed:32047033). Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-287 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:32047033). Deubiquitinated by USP30 (By similarity). http://togogenome.org/gene/10090:Supt20 ^@ http://purl.uniprot.org/uniprot/Q7TT00 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the SPT20 family.|||Interacts with ATG9A (By similarity). Interacts with MAPK14.|||Mice show gastrulation defects in which mesoderm migration is defective due to deficiency in E-cadherin protein down-regulation in the primitive streak. A weaker mutation named droopy eye (drey), which affects splicing causes incompletely penetrant defects in neural tube closure, eye development and gastrulation.|||Required for MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) activation during gastrulation. Required for down-regulation of E-cadherin during gastrulation by regulating E-cadherin protein level downstream from NCK-interacting kinase (NIK) and independently of the regulation of transcription by FGF signaling and Snail. Required for starvation-induced ATG9A trafficking during autophagy.|||Ubiquitously expressed throughout development. http://togogenome.org/gene/10090:Appl2 ^@ http://purl.uniprot.org/uniprot/Q3TVI6|||http://purl.uniprot.org/uniprot/Q8K3G9 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Decreases steadily in response to lipopolysaccharide (LPS).|||Early endosome membrane|||Endosome membrane|||Expressed in insulin-target tissues including skeletal muscle, liver, fat, and brain. Highly expressed in kidney and pancreas (PubMed:19661063). Abundantly expressed in the ventromedial hypothalamus (VMH), barely detectable in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the hypothalamus. Also expressed in pancreatic beta-cells (PubMed:29467283).|||Homodimer. Homotetramer (By similarity). Binds RAB5A/Rab5 through an N-terminal domain (PubMed:25568335). This interaction is essential for its recruitment to endosomal membranes as well as its role in cell proliferation. Binds subunits of the NuRD/MeCP1 complex (By similarity). Interacts with FSHR; interaction is independent of follicle stimulating hormone stimulation (By similarity). Interacts with APPL1; the interaction is decreased by adiponectin in a time-dependent manner (PubMed:19661063, PubMed:25328665). Forms a complex comprising APPL1, RUVBL2, CTNNB1, HDAC1 and HDAC2; interaction reduces interaction between CTNNB1, HDAC1, HDAC2 and RUVBL2 leading to the decrease of deacetylase activity of this complex; affects the recruitment of repressive complexes to the Wnt target genes (By similarity). Interacts (via BAR domain) with TBC1D1; interaction is dependent of TBC1D1 phosphorylation at 'Ser-235'; interaction diminishes the phosphorylation of TBC1D1 at 'Thr-596', resulting in inhibition of SLC2A4 translocation and glucose uptake (PubMed:24879834). Interacts with ANXA2; targets APPL2 to endosomes and acting in parallel to RAB5A (By similarity). Interacts with RAB31 (in GTP-bound form); interaction contributes to or enhances recruitment of APPL2 to the phagosomes; interaction enhances Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (PubMed:25568335). Interacts with PIK3R1; forms a complex with PIK3R1 and APPL1 (PubMed:25328665). Interacts (via BAR domain) with ADIPOR1; hinders the accessibility of APPL1 to ADIPOR1; negatively regulates adiponectin signaling; ADIPOQ dissociates this interaction and facilitates the recruitment of APPL1 to ADIPOR1 (PubMed:19661063). Interacts (via BAR domain) with ADIPOR2; ADIPOQ dissociates this interaction (PubMed:19661063).|||Membrane|||Mice have normal food intake, body weight, and fasting glucose and insulin levels (PubMed:24879834). Mice are viable and grow normally to adulthood (PubMed:26445298). Appl1 and Appl2 double knockout mice are viable and grossly normal with regard to reproductive potential and postnatal growth (PubMed:26445298). Reduced survival rate after injection of LPS (PubMed:25328665). Conditional knockout mice Appl2 in pancreatic beta-cells and/or ventromedial hypothalamus (VMH) have no obvious effect on circulating level of insulin, body weight, food intake, respiratory exchange ratio (RER), and locomotor activity, but gradually increased adiposity and diminished energy expenditure. Mice exhibit cold intolerance and impairment of cold-induced thermogenesis, beiging program, and SNS outflow in subcutaneous white adipose tissue (sWAT). Conditionnal knockout mice Appl2 in ventromedial hypothalamus (VMH) have the same phenotype as above (PubMed:29467283).|||Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (PubMed:25568335, PubMed:27219021, PubMed:25328665, PubMed:19661063, PubMed:29467283). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (By similarity). Plays a role in immune response by modulating phagocytosis, inflammatory and innate immune responses (PubMed:25568335, PubMed:27219021, PubMed:25328665). In macrophages, enhances Fc-gamma receptor-mediated phagocytosis through interaction with RAB31 leading to activation of PI3K/Akt signaling (PubMed:25568335). In response to LPS, modulates inflammatory responses by playing a key role on the regulation of TLR4 signaling and in the nuclear translocation of RELA/NF-kappa-B p65 and the secretion of pro- and anti-inflammatory cytokines (PubMed:27219021). Also functions as a negative regulator of innate immune response via inhibition of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (PubMed:25328665). Plays a role in endosomal trafficking of TGFBR1 from the endosomes to the nucleus (By similarity). Plays a role in cell metabolism by regulating adiponectin and insulin signaling pathways and adaptative thermogenesis (PubMed:19661063, PubMed:29467283) (By similarity). In muscle, negatively regulates adiponectin-simulated glucose uptake and fatty acid oxidation by inhibiting adiponectin signaling pathway through APPL1 sequestration thereby antagonizing APPL1 action (PubMed:19661063). In muscles, negativeliy regulates insulin-induced plasma membrane recruitment of GLUT4 and glucose uptake through interaction with TBC1D1 (By similarity). Plays a role in cold and diet-induced adaptive thermogenesis by activating ventromedial hypothalamus (VMH) neurons throught AMPK inhibition which enhances sympathetic outflow to subcutaneous white adipose tissue (sWAT), sWAT beiging and cold tolerance (PubMed:29467283). Also plays a role in other signaling pathways namely Wnt/beta-catenin, HGF and glucocorticoid receptor signaling (PubMed:28965332, PubMed:29675572, PubMed:26445298). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (By similarity). May affect adult neurogenesis in hippocampus and olfactory system via regulating the sensitivity of glucocorticoid receptor (PubMed:28965332, PubMed:29675572). Required for fibroblast migration through HGF cell signaling (PubMed:26445298).|||Nucleus|||The BAR domain is necessary and sufficient for mediating homotypic and heterotypic interactions; associates with cytoplasmic membrane structures; mediates interaction with TBC1D1 and ADIPOR1 (PubMed:24879834, PubMed:19661063). The PH and PID domains mediate phosphoinositide binding. The PID domain mediates phosphatidylserine binding and allows localization to cytosolic membrane structures and nucleus. The PH domain allows localization to the plasma membrane, cytosolic vesicles and distinct nuclear and perinuclear structures and is sufficient for RUVBL2 interaction (By similarity).|||phagosome|||phagosome membrane|||ruffle|||ruffle membrane http://togogenome.org/gene/10090:Nop14 ^@ http://purl.uniprot.org/uniprot/Q8C539|||http://purl.uniprot.org/uniprot/Q8R3N1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOP14 family.|||Component of the ribosomal small subunit (SSU) processome.|||Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm (By similarity).|||Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm.|||nucleolus http://togogenome.org/gene/10090:Lefty2 ^@ http://purl.uniprot.org/uniprot/P57785 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ At the primitive streak stage (7.0 dpc), expressed in the emerging mesoderm. By 8.0 dpc, expressed exclusively on the left side of developing embryos with expression predominantly in the lateral-plate mesoderm (LPM). Weak expression in the prospective floor plate (PFP).|||Belongs to the TGF-beta family.|||Required for left-right asymmetry determination of organ systems in mammals.|||Secreted|||The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner. http://togogenome.org/gene/10090:Defb6 ^@ http://purl.uniprot.org/uniprot/Q91VD6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Expressed constitutively and induced by lipopolysaccharide (LPS).|||Has potent antibacterial activity against E.coli (ATCC 25922).|||Predominantly expressed in skeletal muscle, also expressed in esophagus, tongue, and trachea. Also expressed in lung when induced by lipopolysaccharide.|||Secreted http://togogenome.org/gene/10090:Bcorl1 ^@ http://purl.uniprot.org/uniprot/A2AQH4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BCOR family.|||Interacts with PCGF1, forming heterodimers (By similarity). The PCGF1-BCORL1 heterodimeric complex interacts with the KDM2B-SKP1 heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (By similarity). Interacts with CTBP1, HDAC4, HDAC5 and HDAC7 (By similarity).|||Nucleus|||Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence specific DNA-binding proteins such as BCL6. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor (By similarity). http://togogenome.org/gene/10090:Cxcl1 ^@ http://purl.uniprot.org/uniprot/A2RTH0|||http://purl.uniprot.org/uniprot/P12850 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||By platelet-derived growth factor. In lung, by lipopolysaccharide or inflammation (By similarity).|||Has chemotactic activity for neutrophils. Contributes to neutrophil activation during inflammation (By similarity). Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. KC(5-72) shows a highly enhanced hematopoietic activity.|||Secreted|||The N-terminal processed form KC(5-72) is produced by proteolytic cleavage after secretion from bone marrow stromal cells. http://togogenome.org/gene/10090:Six6 ^@ http://purl.uniprot.org/uniprot/B2RSE8|||http://purl.uniprot.org/uniprot/Q9QZ28 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SIX/Sine oculis homeobox family.|||Expression is first detected in the embryo at 8 dpc.|||In the developing embryo, expressed mainly in the ventral optic stalk, optic chiasma, the neural retina and the primordial tissues that give rise to the pituitary/hypothalamus axis. Not expressed in the lens placode.|||Interacts with TLE4 and TLE5.|||May be involved in eye development.|||Nucleus http://togogenome.org/gene/10090:Sufu ^@ http://purl.uniprot.org/uniprot/Q3U0Z8|||http://purl.uniprot.org/uniprot/Q9Z0P7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SUFU family.|||Complete embryonic lethality at about 10.5 dpc due to defects in neural tube closure, abnormal somites and abnormal heart looping (PubMed:16155214, PubMed:16459298). Heterozygous mice are born at the expected Mendelian rate and are fertile. After 1.5 years, they develop a skin phenotype characterized by ventral alopecia, increased pigmentation, with papules and nodules on paws and tail (PubMed:16459298).|||Cytoplasm|||May form homodimers (By similarity). Interacts with ULK3; inactivating the protein kinase activity of ULK3. Interacts with RAB23 (By similarity). Part of a DNA-bound corepressor complex containing SAP18, GLI1 and SIN3 (PubMed:11960000). Part of a complex containing CTNNB1 (PubMed:11477086). Binds BTRC, GLI2, GLI3, SAP18 and STK36 (PubMed:20360384, PubMed:23034632). Binds both free and DNA-bound GLI1 (PubMed:10531011). Interacts with KIF7 (PubMed:19592253). Interacts with GLI3FL and this interaction regulates the formation of either repressor or activator forms of GLI3 (PubMed:20360384). Its association with GLI3FL is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A (PubMed:20360384).|||Negative regulator in the hedgehog signaling pathway. Down-regulates GLI1-mediated transactivation of target genes. Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome. Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein. Negative regulator of beta-catenin signaling. Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full-length form of GLI3 (GLI3FL). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A).|||Negative regulator in the hedgehog/smoothened signaling pathway (PubMed:16155214, PubMed:16459298). Down-regulates GLI1-mediated transactivation of target genes (PubMed:11960000). Part of a corepressor complex that acts on DNA-bound GLI1 (PubMed:11960000). May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome (By similarity). Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein (PubMed:10531011, PubMed:16459298). Negative regulator of beta-catenin signaling (PubMed:11477086). Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full-length form of GLI3 (GLI3FL) (PubMed:10531011, PubMed:20360384). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state (PubMed:10531011, PubMed:20360384). Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R (PubMed:10531011, PubMed:20360384). When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A) (PubMed:10531011, PubMed:20360384). Required for normal embryonic development (PubMed:16155214, PubMed:16459298). Required for the proper formation of hair follicles and the control of epidermal differentiation (PubMed:16155214, PubMed:16459298, PubMed:23034632).|||Nucleus|||Phosphorylation at Ser-342, Ser-346, Ser-352 and Thr-353 prevents ubiquitination by the SCF(FBXL17) complex.|||Polyubiquitinated at Lys-257 by the SCF(FBXL17) complex, leading to its subsequent degradation and allowing the release of GLI1 for proper hedgehog/smoothened signal transduction. Ubiquitination is impaired by phosphorylation at Ser-342, Ser-346, Ser-352 and Thr-353.|||Widely expressed in adult and fetal tissues. http://togogenome.org/gene/10090:Tll2 ^@ http://purl.uniprot.org/uniprot/Q9WVM6 ^@ Cofactor|||Developmental Stage|||Function|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Expressed at 7.5 dpc, in a limited way, in the posterior portion of the egg cylinder in the nascent mesoderm streaming off the primitive streak. At the distant end of the embryo cylinder, expression ended at the node. Later in the development, expression seems to be limited to developing skeletal muscle and central nervous system.|||Protease which specifically processes pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.|||Secreted http://togogenome.org/gene/10090:Mybl1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J132|||http://purl.uniprot.org/uniprot/E9QLX9|||http://purl.uniprot.org/uniprot/P51960 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity).|||During embryogenesis it is predominantly expressed in several regions of the developing central nervous system and the urogenital ridge. Expression in the CNS is confined to the neural tube, the hindbrain, the neural retina and the olfactory epithelium, and coincides with the presence of proliferating immature neuronal precursor cells. In the adult mouse, A-Myb is expressed at high levels in type A spermatogonia (stem cells), and preleptotene and pachytene spermatocytes, with concomitant down-regulation of expression upon terminal differentiation of these cells into mature spermatozoa, and in B lymphocytes located in germinal centers of the spleen (PubMed:7813437, PubMed:8084617). Present in mid-late pachytene and diplotene spermatocytes, but not in late zygotene/early pachytene cells (at protein level) (PubMed:21750041).|||Nucleus|||Predominantly in the testis. Very low levels in the ovaries, spleen and brain.|||Transcription factor that specifically recognizes the sequence 5'-YAAC[GT]G-3' (PubMed:7813437, PubMed:23523368). Acts as a master regulator of male meiosis by promoting expression of piRNAs: activates expression of both piRNA precursor RNAs and expression of protein-coding genes involved in piRNA metabolism, such as PIWIL1 (PubMed:21750041, PubMed:23523368). The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons, which is essential for the germline integrity (PubMed:23523368). Transcriptional activator of SOX30 (PubMed:29848638). http://togogenome.org/gene/10090:Fitm1 ^@ http://purl.uniprot.org/uniprot/Q91V79 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FIT family. FIT1 subfamily.|||Endoplasmic reticulum membrane|||Knockout mice show no significant differences in heart size or function.|||Plays an important role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis (PubMed:18160536, PubMed:22106267) (By similarity). Directly binds to diacylglycerol (DAGs) and triacylglycerol (PubMed:22106267) (By similarity).|||Predominantly expressed in skeletal muscle and at lower levels in the heart (at protein level). In the heart, mRNA expression levels do not correlate well with protein levels, suggesting post-transcriptional regulation in this organ. http://togogenome.org/gene/10090:Pmm1 ^@ http://purl.uniprot.org/uniprot/O35621|||http://purl.uniprot.org/uniprot/Q545Q8|||http://purl.uniprot.org/uniprot/Q91W01 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic PMM family.|||Cytoplasm|||Highly expressed at 17 dpc in most organs (at protein level).|||Homodimer.|||IMP, a metabolite whose concentration is elevated in anoxia, inhibits phosphomannomutase and phosphoglucomutase activities and strongly enhances glucose-1,6-bisphosphatase activity.|||Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.|||Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. In addition, may be responsible for the degradation of glucose-1,6-bisphosphate in ischemic brain.|||Mice are viable and fertile and develop normally.|||Present in brain, where it is restricted to neuronal cell bodies. Present at lower levels in pancreas, liver, lung, gonads, uterus, adrenal glands and pituitary (at protein level). Undetectable in intestine. http://togogenome.org/gene/10090:Srsf2 ^@ http://purl.uniprot.org/uniprot/Q62093 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation on Lys-52 by KAT5/TIP60 promotes its proteasomal degradation. This effect is counterbalanced by HDAC6, which positively controls SRSF2 protein level by deacetylating it and preventing its proteasomal degradation (By similarity).|||Belongs to the splicing factor SR family.|||Expressed in all the tissues examined; liver, kidney, spleen, heart, lung and brain.|||Extensively phosphorylated on serine residues in the RS domain. Phosphorylated by SRPK2 and this causes its redistribution from the nuclear speckle to nucleoplasm and controls cell fate decision in response to cisplatin treatment. KAT5/TIP60 inhibits its phosphorylation by preventing SRPK2 nuclear translocation (By similarity).|||Interacts with CCNL1 and CCNL2. Interacts with SCAF11. Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus) (By similarity). In vitro, self-associates and binds SRSF1/SFRS1 (ASF/SF2), SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with BRDT.|||Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA (By similarity). Can bind to the myelin basic protein (MBP) gene MB3 regulatory region and increase transcription of the mbp promoter in cells derived from the CNS. The phosphorylated form (by SRPK2) is required for cellular apoptosis in response to cisplatin treatment (By similarity).|||Nucleus|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Zbtb49 ^@ http://purl.uniprot.org/uniprot/Q8BXX2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Interacts with EP300, KAT5/Tip60 and ZBTB17. The interaction with EP300 is direct and leads to synergistic induction of CDKN1A. On the CDKN1A promoter, forms a complex with ZBTB17; this interaction leads to additive CDKN1A transactivation. The interaction with ZBTB17 may block ZBTB17 repressor activity.|||Nucleus|||Transcription factor. Inhibits cell proliferation by activating either CDKN1A/p21 transcription or RB1 transcription.|||Widely expressed, with highest levels in white adipose tissue and kidney, intermediate levels in brain, liver and heart, and lowest levels in spleen, brown adipose tissue and muscle. http://togogenome.org/gene/10090:Psmc1 ^@ http://purl.uniprot.org/uniprot/P62192|||http://purl.uniprot.org/uniprot/Q542I9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC1 and few additional components. Interacts with SCA7. Interacts with NGLY1. Interacts with PAAF1.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC1 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.|||Cytoplasm|||Membrane|||Nucleus http://togogenome.org/gene/10090:Adgrg6 ^@ http://purl.uniprot.org/uniprot/Q6F3F9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Deficient mice die during organogenesis. Mutant embryos show signs of myocardial wall thinning, hypotrabeculation, defective mitochondrial and circulatory failure.|||Expressed at high levels in the heart, somite and otic vesicle during embryogenesis and in adult lung.|||G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane. Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons these functions are mediated via G-protein-signaling pathways (PubMed:24227709, PubMed:21613327). Regulates also neural, cardiac and ear development via G-protein- and/or N-terminus-dependent signaling. May act as a receptor for PRNP which may promote myelin homeostasis (PubMed:27501152).|||Interacts with Laminin-2; this interaction stabilizes the receptor in an inactive state (PubMed:25695270). Laminin-2 polymerization could facilitate ADGRG6-NTF removal, thereby exposing the tethered agonist to drive myelination (PubMed:25695270). Interacts with PRNP (PubMed:27501152).|||Plays an important role in heart developmention (PubMed:24082093). Necessary and sufficient for axon sorting by Schwann cells independently of the ADGRG6-CTF (PubMed:25695270).|||Proteolytically cleaved into 2 conserved sites: one in the GPS domain (S1 site) and the other in the middle of the extracellular domain (S2 site). The proteolytic cleavage at S1 site generates an N-terminal fragment (NTF) and a seven-transmembrane-containing C-terminal fragment (CTF). The membrane-bound CTF can act as an independent receptor and the soluble NTF can act as a ligand or coreceptor. Furin is involved in the cleavage of the S2 site generating a soluble fragment. Processing at the GPS domain occurred independent of and probably prior to the cleavage at the S2 site. Proteolytic cleavage is required for activation of the receptor (By similarity). http://togogenome.org/gene/10090:Cyp11b1 ^@ http://purl.uniprot.org/uniprot/Q3TG86|||http://purl.uniprot.org/uniprot/Q3UQH5 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Atad3a ^@ http://purl.uniprot.org/uniprot/Q925I1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family.|||Can form homooligomers. Homodimer formation at the N-terminus may be regulated by ATP and is required for the interaction with the inner surface of the mitochondrial outer membrane and correct mitochondrial homeostasis. Interacts with components of the mitochondrial ribosome and with other proteins involved in mitochondrial RNA metabolism. May also interact with protein involved in lipid metabolism, including STARD9. May interact with FAM210A. Interacts with GADD45GIP1. Interacts with S100B in a Ca(+2)- and Zn(+2)-dependent manner; this interaction probably occurs in the cytosol prior to mitochondrial targeting. S100B could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. Interacts with HSP60/HSPD1. Forms heterooligomers with ATAD3B; this interaction may affect ATAD3A activity. Interacts with CLPB.|||Essential for mitochondrial network organization, mitochondrial metabolism and cell growth at organism and cellular level. May play an important role in mitochondrial protein synthesis. May also participate in mitochondrial DNA replication. May bind to mitochondrial DNA D-loops and contribute to nucleoid stability. Required for enhanced channeling of cholesterol for hormone-dependent steroidogenesis. Involved in mitochondrial-mediated antiviral innate immunity.|||Expressed in heart, spleen, kidney, liver and at smaller levels, in lung and muscle (at protein level).|||Mitochondrion inner membrane|||The transmembrane domain and a C-terminal adjacent region contain all information necessary for mitochondrial targeting.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Mapre2 ^@ http://purl.uniprot.org/uniprot/E9Q6X0|||http://purl.uniprot.org/uniprot/Q8R001 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAPRE family.|||Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1 (By similarity).|||Cytoplasm|||Interacts with DCTN1. Interacts with APC (via C-terminal). Interacts with monomeric and polymerized tubulin (By similarity). Interacts with SLAIN1 (PubMed:21646404). Interacts (via the N-terminal region) with BAG1 (By similarity).|||May be involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes. May play a role in cell migration (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Fam110a ^@ http://purl.uniprot.org/uniprot/Q8R184 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM110 family.|||Cytoplasm|||May interact with CSPP1.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Fbxw7 ^@ http://purl.uniprot.org/uniprot/Q8VBV4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Homodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (By similarity). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11735228). Interacts (via F-box domain) with SKP1 (PubMed:11735228). Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1 (By similarity). Interacts with cyclin-E (CCNE1 or CCNE2) (By similarity). Interacts with PSEN1 (By similarity). Forms a trimeric complex with NOTCH1 and SGK1 (By similarity). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD (PubMed:11425854, PubMed:11461910). Interacts with NOTCH2 intracellular domain (N2ICD) (By similarity). Interacts with MYC (when phosphorylated) (By similarity). Interacts with USP28, counteracting ubiquitination of MYC (By similarity). Interacts (when phosphorylated at Thr-208) with PIN1, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity). Interacts with UBE2QL1 (By similarity). Interacts with FAM83D; promotes FBXW7 degradation (By similarity). Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (By similarity). Interacts with JUN (By similarity). Found in a complex with JUN and PRR7 (By similarity). Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation, promoting its phosphorylation and transcriptional activity (By similarity). Interacts with NFE2L1 (PubMed:21953459). Interacts with NR1D1 (By similarity). Interacts with RICTOR; mediates RICTOR ubiquitination and degradation (By similarity). Interacts with USP38, counteracting ubiquitination of MYC (By similarity).|||Phosphorylation at Thr-208 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation. Phosphorylated by ATM at Ser-26 in response to DNA damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:21953459, PubMed:22748924). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:22748924). Mediates ubiquitination and subsequent degradation of CCNE1 and MYC (PubMed:22748924). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, MLST8, RICTOR and probably PSEN1 (By similarity). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (By similarity). SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1 (PubMed:21953459). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (By similarity). The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining (By similarity).|||The F-box domain mediates interaction with SKP1.|||The WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex.|||Ubiquitinated: autoubiquitinates following phosphorylation at Thr-208 and subsequent interaction with PIN1 (By similarity). Ubiquitination leads to its proteasomal degradation (PubMed:22748924).|||Whole body FBW7 knockout is embryonic lethal. Conditional knockout mice in which FBW7 expression is specifically abolished in osteoclasts display severe bone resorption, bone fragility and low bone mass (PubMed:29149593). Conditional knockout in liver reduces the amplitude of the diurnal expression of many core clock genes and the altered expression of a large number of genes controlling liver metabolic pathways (PubMed:27238018).|||Widely expressed with highest levels in brain, heart and testis.|||nucleoplasm http://togogenome.org/gene/10090:Ndufs1 ^@ http://purl.uniprot.org/uniprot/Q91VD9 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-84 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the complex I 75 kDa subunit family.|||Binds 1 [2Fe-2S] cluster per subunit.|||Binds 2 [4Fe-4S] clusters per subunit.|||Brain. More abundant in neurons than in astrocytes (at protein level).|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits (By similarity). This is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme (By similarity). Complex I associates with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:27799543). In astrocytes, less complex I is assembled into supercomplexes as compared to neurons (PubMed:27799543). Interacts with MDM2 (By similarity). Interacts with AKAP1 (PubMed:32072193).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:27799543, PubMed:32072193). Essential for catalysing the entry and efficient transfer of electrons within complex I (PubMed:27799543). Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:27799543).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Slc6a19 ^@ http://purl.uniprot.org/uniprot/Q3KN89|||http://purl.uniprot.org/uniprot/Q9D687 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A19 subfamily.|||Cell membrane|||Deficient mice exhibit reduced growth, impaired body weight control, insulin response and amino acid absorption and excretion.|||Interacts in a tissue-specific manner with ACE2 in small intestine and with CLTRN in the kidney (PubMed:19185582, PubMed:17167413). Interacts with CLTRN; this interaction is required for trafficking of SLC6A19 to the plasma membrane and for its catalytic activation in kidneys (PubMed:17167413). Interacts with ACE2; this interaction is required for trafficking of SLC6A19 to the plasma membrane and for its catalytic activation in intestine (PubMed:19185582). Interacts with ANPEP; the interaction positively regulates its amino acid transporter activity (PubMed:22677001).|||Membrane|||Predominantly expressed in kidney and small intestine (at protein level) (PubMed:15044460, PubMed:19185582). Expressed in the intestinal brush border (at protein level) (PubMed:22677001). Expression not observed in other organs, such as lung, skeletal muscle, brain, liver and pancreas. In kidney, expression is localized in the renal cortex but not in the medulla. Substantial amounts of expression in the proximal tubules. The distal nephron segments and the glomeruli are consistently negative. In the small intestine, expression is exclusively localized in villus enterocytes. High resolution of the hybridization-positive villi reveals a gradient of expression with the highest levels in apical cells. Not detected in crypt cells or in any other cell types of the small intestine.|||Transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells (PubMed:18424768, PubMed:17167413, PubMed:26240152, PubMed:19185582, PubMed:15044460). This uptake is sodium-dependent and chloride-independent (PubMed:18424768, PubMed:19185582, PubMed:15044460, PubMed:21636576, PubMed:26240152). Requires CLTRN in kidney or ACE2 in intestine for cell surface expression and amino acid transporter activity (PubMed:18424768, PubMed:17167413, PubMed:19185582, PubMed:22677001). http://togogenome.org/gene/10090:Kcnq5 ^@ http://purl.uniprot.org/uniprot/E9Q9F1|||http://purl.uniprot.org/uniprot/G3UYG5|||http://purl.uniprot.org/uniprot/Q9JK45 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. Therefore, it is important in the regulation of neuronal excitability. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current.|||Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.5/KCNQ5 sub-subfamily.|||Cell membrane|||Heteromultimer with KCNQ3. Heterotetramer with KCNQ1; has a voltage-gated potassium channel activity.|||Membrane|||The activity of this channel is modulated by zinc, pH and volume changes.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Sgk1 ^@ http://purl.uniprot.org/uniprot/E9Q1B0|||http://purl.uniprot.org/uniprot/E9Q8C1|||http://purl.uniprot.org/uniprot/Q9WVC6 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Homodimer; disulfide-linked. Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1, MAP2K2/MEK2, NEDD4, NEDD4L, MAPT/TAU, MAPK7, CREB1, SLC9A3R2/NHERF2 and KCNJ1/ROMK1 (By similarity). Forms a trimeric complex with FBXW7 and NOTCH1 Associates with the mammalian target of rapamycin complex 2 (mTORC2) via an interaction with MAPKAP1/SIN1.|||Mitochondrion|||Nucleus|||Regulated by phosphorylation. Activated by phosphorylation on Ser-422 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256. Phosphorylation on Ser-397 and Ser-401 are also essential for its activity. Phosphorylation on Ser-78 by MAPK7 is required for growth factor-induced cell cycle progression (By similarity).|||Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis.|||Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-422), need to be phosphorylated for its full activation (By similarity). Phosphorylation at Ser-397 and Ser-401 are also essential for its activity (By similarity). Activated by WNK1, WNK2, WNK3 and WNK4; which promote phosphorylation by mTORC2 (PubMed:20525693).|||Ubiquitinated by NEDD4L; which promotes proteasomal degradation. Ubiquitinated by SYVN1 at the endoplasmic reticulum; which promotes rapid proteasomal degradation and maintains a high turnover rate in resting cells (By similarity).|||Up-regulated by tumor suppressor p53 in mammary epithelial tumor cells. http://togogenome.org/gene/10090:Ttll7 ^@ http://purl.uniprot.org/uniprot/A4Q9F0 ^@ Caution|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin--tyrosine ligase family.|||Highly expressed in brain, testis and trachea (PubMed:17499049). Expressed in brain, heart, kidney, liver, lung, muscle and trachea (PubMed:17499049). In the brain, highly expressed in hippocampus, thalamus, olfactory bulb and cerebellum cortex, corpus callosum and striatum (PubMed:16901895, PubMed:17499049).|||Interacts with both alpha- and beta-tubulin (via C-terminal tubulin tails).|||May be due to an intron retention.|||Perikaryon|||Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin (PubMed:17499049, PubMed:16901895, PubMed:19152315). Mediates both ATP-dependent initiation and elongation steps of the polyglutamylation reaction (PubMed:17499049, PubMed:16901895, PubMed:19152315). Preferentially modifies the beta-tubulin tail over an alpha-tail (PubMed:17499049, PubMed:16901895, PubMed:19152315). Competes with monoglycylase TTLL3 for modification site on beta-tubulin substrate, thereby creating an anticorrelation between glycylation and glutamylation reactions (By similarity). Required for neurite growth; responsible for the strong increase in tubulin polyglutamylation during postnatal neuronal maturation (PubMed:16901895).|||The enzyme uses its core to engage the disordered anionic tails of alpha- and beta-tubulin and the flexible c-MTBD (cationic microtubule binding domain) region to bind the microtubule and position itself for beta-tail modification. The c-MTBD region is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on alpha-tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.|||Was initially though to be involved in the side-chain initiation step of the polyglutamylation reaction rather than in the elongation step (PubMed:17499049). However, it was later shown to be involved in both steps (PubMed:19152315).|||cilium|||cilium basal body|||dendrite http://togogenome.org/gene/10090:Mgarp ^@ http://purl.uniprot.org/uniprot/Q8VI64 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the ovary, testis, brain, adrenal glands and the compartments of the visual nervous system. Expressed in corneal endothelium (CE) (at protein level). Expressed in steroidogenic tissues with the highest level of expression observed in the adrenal gland. Weakly expressed in placenta. Weakly expressed in astrocytes and neurons under normoxia. Strongly expressed in astrocytes and neurons under hypoxia. Expressed in each layer of the retina, with particularly higher staining in the inner segment of the photoreceptor (IS), the outer plexiform layer (OPL) and the ganglion cell layer (GCL).|||Interacts with RHOT1/Miro-1, RHOT2/Miro-2, TRAK1/OIP106 and TRAK2/GRIF1.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Plays a role in the trafficking of mitochondria along microtubules (PubMed:19325000). Regulates the kinesin-mediated axonal transport of mitochondria to nerve terminals along microtubules during hypoxia (PubMed:19325000). Participates in the translocation of TRAK2/GRIF1 from the cytoplasm to the mitochondrion (PubMed:19325000). Also plays a role in steroidogenesis through maintenance of mitochondrial abundance and morphology (PubMed:19528298). Plays an inhibitory role during neocortex development by regulating mitochondrial morphology, distribution and motility in neocortical neurons (PubMed:24323429).|||Reduction of mitochondrial motion in the anterograde direction and increase of mitochondrial motion in the retrograde direction in response to hypoxia (PubMed:19528298). The number of motile mitochondria is not altered (PubMed:19528298). Neocortical neurons exhibit a remarkable increase of the dendritic number and the axon length (PubMed:24323429). Neuronal cells show an increase in the percentage of round mitochondria and a decrease in the percentage of rod or tubular mitochondria (PubMed:24323429).|||Up-regulated by chorionic gonadotropin in ovary. Up-regulated by hypoxia in a HIF-1A-dependent manner in neurons and astrocytes. Up-regulated during gonad development after birth, probably under the regulation of hormones derived from the hypothalamic-pituitary-gonadal (HPG) axis. http://togogenome.org/gene/10090:Tnfaip6 ^@ http://purl.uniprot.org/uniprot/O08859|||http://purl.uniprot.org/uniprot/Q3USX6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in cumulus cell-oocyte complexes during expansion.|||Expressed in epiphyseal and metaphyseal bone marrow of both the femur and tibia (at protein level).|||Interacts (via Link domain) with inter-alpha-inhibitor (I-alpha-I) component bikunin. Interacts with ITIH2/HC2; this interaction is required for transesterification of the HC to hyaluronan. Interacts (via Link and CUB domains) with ITIH1. Chondroitin sulfate may be required for the stability of the complex. Interacts (via Link domain) with various C-X-C and C-C chemokines including PF4, CXCL8, CXCL11, CXCL12, CCL2, CCL7, CCL19, CCL21, and CCL27; this interaction interferes with chemokine binding to glycosaminoglycans. Interacts (primarily via Link domain) with BMP2; this interaction is inhibited by hyaluronan. Interacts (via both Link and CUB domains) with TNFSF11. Interacts (via CUB domain) with FN1 (via type III repeats 9-14); this interaction enhances fibronectin fibril assembly. TNFAIP6 may act as a bridging molecule between FN1 and THBS1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Major regulator of extracellular matrix organization during tissue remodeling (By similarity). Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin (By similarity). Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization (PubMed:12668637). Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling (By similarity). Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation. In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium (By similarity). Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts. Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation (PubMed:18586671) (By similarity).|||Mutant female mice are infertile due to impaired cumulus oophorus expansion upon gonadotropin surge (PubMed:12668637). Mutant mice have twice the bone mass of wild-type littermates. They show increased trabecular number and trabecular thickness (PubMed:18586671).|||Secreted|||The CUB domain is necessary for calcium ion binding and transesterification reaction. It is required for binding to FN1.|||The Link domain interacts with various extracellular matrix components, including heparin, heparan sulfates, hyaluronan and I-alpha-I complex. It is required for binding to various chemokines. http://togogenome.org/gene/10090:M6pr ^@ http://purl.uniprot.org/uniprot/P24668 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Binds GGA1, GGA2 and GGA3 (By similarity).|||Lysosome membrane|||The extracellular domain is homologous to the repeating units (of approximately 147 AA) of the cation-independent mannose 6-phosphate receptor.|||This receptor has optimal binding in the presence of divalent cations.|||Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelyosomal compartment where the low pH mediates the dissociation of the complex. http://togogenome.org/gene/10090:Car15 ^@ http://purl.uniprot.org/uniprot/Q99N23 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-carbonic anhydrase family.|||Repressed by coumarins.|||Reversible hydration of carbon dioxide.|||Secreted http://togogenome.org/gene/10090:Ms4a14 ^@ http://purl.uniprot.org/uniprot/A0A087WSD2 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Gpr65 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Y2|||http://purl.uniprot.org/uniprot/Q3UQ35|||http://purl.uniprot.org/uniprot/Q3UZ41|||http://purl.uniprot.org/uniprot/Q61038 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By glucocorticoids, during apoptosis of immature thymocytes.|||Cell membrane|||Detected in thymus and at low levels in spleen.|||Membrane|||Mutant mice are healthy with no signs of spontaneous colitis or inflammation, however are more susceptible to bacteria-induced colitis in comparison to the wild type.|||Receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (By similarity). Plays a role in immune response by maintaining lysosome function and supporting phagocytosis-mediated intracellular bacteria clearance (PubMed:27287411). May have a role in activation-induced cell death or differentiation of T-cells (PubMed:8599842). http://togogenome.org/gene/10090:Zfp709 ^@ http://purl.uniprot.org/uniprot/Q8C0I0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Cytoplasm|||Interacts with PRMT5. Interacts with FBXO10. Interacts with FBXO11.|||Nucleus|||Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs. Plays a role in the development, retention and long-term establishment of adaptive and innate tissue-resident lymphocyte T cell types in non-lymphoid organs, such as the skin and gut, but also in other nonbarrier tissues like liver and kidney, and therefore may provide immediate immunological protection against reactivating infections or viral reinfection. Binds specifically to the PRDI element in the promoter of the beta-interferon gene. Drives the maturation of B-lymphocytes into Ig secreting cells. Associates with the transcriptional repressor ZNF683 to chromatin at gene promoter regions. http://togogenome.org/gene/10090:Tmem238 ^@ http://purl.uniprot.org/uniprot/A9JSM3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Nodal ^@ http://purl.uniprot.org/uniprot/P43021 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Essential for mesoderm formation and axial patterning during embryonic development.|||Expressed in the node during gastrulation. Expression is first detected in primitive streak-stage embryos at about the time of mesoderm formation. It then becomes highly localized in the node at the anterior of the primitive streak.|||Homodimer; disulfide-linked.|||Secreted http://togogenome.org/gene/10090:Kcnmb2 ^@ http://purl.uniprot.org/uniprot/Q9CZM9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB2 subfamily.|||Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB2 per KCNMA1 tetramer (By similarity).|||Membrane|||N-glycosylated.|||Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Acts as a negative regulator that confers rapid and complete inactivation of KCNMA1 channel complex (By similarity).|||The ball and chain domain mediates the inactivation of KCNMA1. It occludes the conduction pathway of KCNMA1 channels, and comprises the pore-blocking ball domain (residues 1-17) and the chain domain (residues 20-45) linking it to the transmembrane segment. The ball domain is made up of a flexible N-terminus anchored at a well ordered loop-helix motif. The chain domain consists of a 4-turn helix with an unfolded linker at its C-terminus (By similarity). http://togogenome.org/gene/10090:Lhb ^@ http://purl.uniprot.org/uniprot/G3X9G6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycoprotein hormones subunit beta family.|||Secreted http://togogenome.org/gene/10090:Pttg1 ^@ http://purl.uniprot.org/uniprot/Q9CQJ7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the securin family.|||Cytoplasm|||During the stages 11.5-13.5 dpc it is expressed in most tissues of the embryo. Within the telencephalon, it is exclusively expressed inside of the ventricular zone (VZ). The expression reaches its peak by 15.5 dpc and starts to decrease by 18.5 dpc, and is not detectable in the adult brains. Most of the cells expressing it were found in the lower part of the ventricular zone.|||Interacts with RPS10 and DNAJA1. Interacts with the caspase-like ESPL1, and prevents its protease activity probably by covering its active site. Interacts with p53/TP53 and blocks its activity probably by blocking its binding to DNA. Interacts with the Ku 70 kDa subunit of ds-DNA kinase. Interacts with PTTG1IP (By similarity).|||Nucleus|||Phosphorylated at Ser-162 by CDC2 during mitosis.|||Phosphorylated in vitro by ds-DNA kinase.|||Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of p53/TP53. The negative regulation of p53/TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation (By similarity).|||The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.|||The TEK-boxes are required for 'Lys-11'-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue (By similarity).|||Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties by the anaphase promoting complex (APC) at the onset of anaphase, conducting to its degradation. 'Lys-11'-linked ubiquitination is mediated by the E2 ligase UBE2C/UBCH10 (By similarity). http://togogenome.org/gene/10090:Rpl34 ^@ http://purl.uniprot.org/uniprot/Q9D1R9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL34 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||Endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:H1f3 ^@ http://purl.uniprot.org/uniprot/P43277|||http://purl.uniprot.org/uniprot/Q149Z9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the histone H1/H5 family.|||Chromosome|||Citrullination at Arg-55 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.|||H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter.|||Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||No visible phenotype. Triple-deficient mice (H1-2, H1-3 and H1-4) die by midgestation with a broad range of defects. These embryos have about 50% of the normal ratio of H1 to nucleosomes, demonstrating that critical levels of total H1 histones are essential for mouse embryogenesis.|||Nucleus|||The C-terminal domain is required for high-affinity binding to chromatin. http://togogenome.org/gene/10090:Noc4l ^@ http://purl.uniprot.org/uniprot/Q8BHY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CBF/MAK21 family.|||Nucleus membrane|||nucleolus http://togogenome.org/gene/10090:Bbln ^@ http://purl.uniprot.org/uniprot/P58686 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UPF0184 (EST00098) family.|||Cell junction|||Essential for intermediate filament organization in intestinal cells, interacts with intermediate filament and regulates intestinal lumen morphology.|||cytoskeleton http://togogenome.org/gene/10090:Gas8 ^@ http://purl.uniprot.org/uniprot/Q49MD7|||http://purl.uniprot.org/uniprot/Q60779 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DRC4 family.|||Component of the nexin-dynein regulatory complex (N-DRC) (By similarity). Interacts with microtubules (PubMed:17366626). Interacts with SMO (PubMed:21659505). Interacts (via coiled-coil domains) with RAB3B (in GTP-bound form) (PubMed:18396146). Interacts with DRC1 (By similarity). Interacts with DRC7 (PubMed:31961863).|||Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays an important role in the assembly of the N-DRC linker (By similarity). Plays dual roles at both the primary (or non-motile) cilia to regulate hedgehog signaling and in motile cilia to coordinate cilia movement. Required for proper motile cilia functioning. Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity in a GRK2-dependent manner (PubMed:17366626, PubMed:21659505, PubMed:27472056). May play a role in the spermatozoa motility (PubMed:11751847).|||Cytoplasm|||Expressed during serum starvation or contact inhibition of cells grown in murine fibroblasts.|||Golgi apparatus|||Highly expressed in adult testes and lung. Weakly or not expressed in other tested tissues.|||Mice show primary ciliary dyskinesia (PCD) like symptoms including situs inversus and hydrocephalus. Hydrocephalus starts at postnatal day 5 (P5) and becomes more pronounced as the mice mature, eventually leading to mortality between P14-P21. Development of hydrocephalus is associated with severe impairment of cilia motility on ependymal cells lining the ventricles of the brain.|||Weakly or not expressed in neonates and young adolescents. Then, it is strongly expressed postmeiotically. Accumulates in gametocytes as they approach the lumen of seminiferous tubules and thereafter.|||cilium|||cilium axoneme|||cilium basal body|||cytoskeleton|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Or9s13 ^@ http://purl.uniprot.org/uniprot/Q0VBN7|||http://purl.uniprot.org/uniprot/Q60894 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Psma2 ^@ http://purl.uniprot.org/uniprot/P49722 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||Phosphorylated on tyrosine residues; which may be important for nuclear import.|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. http://togogenome.org/gene/10090:Ldlrad1 ^@ http://purl.uniprot.org/uniprot/D3YYZ1 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Prss38 ^@ http://purl.uniprot.org/uniprot/Q3UKY7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Secreted http://togogenome.org/gene/10090:Spdef ^@ http://purl.uniprot.org/uniprot/Q9WTP3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Expressed in the accessory glands of sex organs including the prostate, seminal vesicle, coagulating gland in males, the oviduct in females, and in intestines. Expression is epithelial-specific.|||Interacts with the DNA-binding domain of the androgen receptor. Interacts with NKX3-1 (By similarity).|||May function as an androgen-independent transactivator of the prostate-specific antigen (PSA) promoter. Binds to 5'-GGAT-3' DNA sequences. May play a role in the regulation of the prostate gland and/or prostate cancer development. Acts as a transcriptional activator for SERPINB5 promoter (By similarity).|||Nucleus http://togogenome.org/gene/10090:Cyp2a4 ^@ http://purl.uniprot.org/uniprot/P15392 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highly active in the 15-alpha-hydroxylation of testosterone. Also active in the 15-alpha-hydroxylation of progesterone and androstenedione. Little or no activity on corticosterone, pregnenolone, dehydroepiandrosterone, estradiol or estriol.|||Kidney and lung. Expressed in liver, with a strong circadian rhythmicity. Circadian expression is regulated by DBP.|||Microsome membrane|||There are only 11 differences between the sequence of testosterone 15-alpha-hydroxylase and that of coumarin 7-hydroxylase. By site-directed mutagenesis it has been shown that modification of position 209 is sufficient to convert the specificity of the two forms of the enzyme. http://togogenome.org/gene/10090:Nr2f1 ^@ http://purl.uniprot.org/uniprot/Q32NY6|||http://purl.uniprot.org/uniprot/Q60632 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Binds DNA as dimer; homodimer and probable heterodimer with NR2F6. Interacts with GTF2B; this interaction is direct. Interacts with COPS2.|||Coup (chicken ovalbumin upstream promoter) transcription factor binds to the ovalbumin promoter and, in conjunction with another protein (S300-II) stimulates initiation of transcription. Binds to both direct repeats and palindromes of the 5'-AGGTCA-3' motif. Represses transcriptional activity of LHCG (By similarity).|||Expression begins in 8.5-day-old embryos, peaks at 14-15 days and declines before birth.|||Nucleus http://togogenome.org/gene/10090:Pgbd5 ^@ http://purl.uniprot.org/uniprot/D3YZI9 ^@ Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ 20-nucleotide gap within coding exon 1.|||Expressed in the brain (at protein level).|||Has been domesticated very early in vertebrate evolution, approximately 500 million years ago, in the common ancestor of cephalochordates and vertebrates.|||Nucleus|||Transposase that mediates sequence-specific genomic rearrangements. http://togogenome.org/gene/10090:Zfp746 ^@ http://purl.uniprot.org/uniprot/Q3U133 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Interacts (via C2H2-type zinc fingers) with PRKN (PubMed:21376232). Interacts with TRIM28 (By similarity).|||Nucleus|||Transcription repressor that specifically binds to the 5'-TATTTT[T/G]-3' consensus sequence on promoters and repress transcription of PGC-1-alpha (PPARGC1A), thereby playing a role in regulation of neuron death.|||Ubiquitinated by PRKN. 'Lys-48'-linked polyubiquitination by PRKN leads to degradation by the proteasome and may play a key role in regulation of neuron death (By similarity).|||Widely expressed. In brain, it is heterogeneously distributed throughout the brain and localizes to neurons, including substantia nigra pars compacta dopamine-containing neurons. Weakly expressed in cerebellum and midbrain (at protein level). http://togogenome.org/gene/10090:Cst7 ^@ http://purl.uniprot.org/uniprot/O89098 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cystatin family.|||Inhibits papain and cathepsin L but with affinities lower than other cystatins. May play a role in immune regulation through inhibition of a unique target in the hematopoietic system.|||Secreted http://togogenome.org/gene/10090:Ncapd2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0H7|||http://purl.uniprot.org/uniprot/Q8K2Z4 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CND1 (condensin subunit 1) family.|||Chromosome|||Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: NCAPH/BRRN1, NCAPD2/CAPD2 and NCAPG. Interacts with histones H1 and H3 (By similarity).|||Contaminating sequence.|||Cytoplasm|||Nucleus|||Phosphorylated by CDK1. Its phosphorylation, as well as that of NCAPH and NCAPG subunits, activates the condensin complex and is required for chromosome condensation (By similarity).|||Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases.|||Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain. May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of non-centromeric ultrafine DNA bridges during anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size.|||The C-terminal domain interacts with histones H1 and H3, and may be responsible for condensin complex targeting to mitotic chromosomes. This domain is independent from the bipartite nuclear localization signal, although they are contained within the same region (By similarity). http://togogenome.org/gene/10090:Krt24 ^@ http://purl.uniprot.org/uniprot/A1L317 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Slc1a3 ^@ http://purl.uniprot.org/uniprot/P56564|||http://purl.uniprot.org/uniprot/Q543U3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.|||Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A3 subfamily.|||Cell membrane|||Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.|||Detected in brain, in Bergmann glia arborising into the molecular layer of the cerebellum (at protein level) (PubMed:15363892). Localized in brain and is highly enriched in the Purkinje cell layer in cerebellum. Intermediate level in lung, low level in spleen, skeletal muscle and testis.|||Glycosylated.|||Homotrimer (By similarity).|||Membrane|||No visible phenotype (PubMed:15363892, PubMed:15390100). Mutant mice display normal locomotion, motor coordination and learning, and globally normal glutamate uptake in brain vesicle preparations (PubMed:15363892). The decay time of glutamate receptor mediated excitatory postsynaptic currents (EPSCs) in cerebellar Purkinje is slightly increased (PubMed:15363892). The decreased rate of glutamate uptake in retina Mueller cells from mutant mice suggests that Slc1a3 accounts for about half of the glutamate uptake activity in wild-type cells (PubMed:15390100). Mice deficient in both Slc1a2 and Slc1a3 die at about 17 dpc (PubMed:16880397).|||Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7903437, PubMed:28032905). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (By similarity). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (PubMed:15363892, PubMed:15390100, PubMed:16880397). http://togogenome.org/gene/10090:Gm10229 ^@ http://purl.uniprot.org/uniprot/O08631 ^@ Similarity|||Subunit ^@ Belongs to the KRTAP type 6 family.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Mgrn1 ^@ http://purl.uniprot.org/uniprot/Q9D074 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated in vitro.|||Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase. Mediates TSG101 monoubiquitination at multiple sites. Plays a role in the regulation of endosome-to-lysosome trafficking. Impairs MC1R- and MC4R-signaling by competing with GNAS-binding to MCRs and inhibiting agonist-induced cAMP production. Does not inhibit ADRB2-signaling. Does not promote MC1R ubiquitination (By similarity). Acts also as a negative regulator of hedgehog signaling (PubMed:29290584).|||Early endosome|||In presomite and early somite stage embryos, most strongly expressed in the node and more weakly in the neuroepithelium. In 6- to 12-somite embryos, strongest expression in the node, symmetrically in the floor plate of the neural tube and in the developing heart; weaker expression in paraxial mesoderm, somites, neuroepithelium, as well as in hind- and foregut pockets. By 9.5 dpc, virtually ubiquitous.|||Interacts with MC1R and MC4R (By similarity). Interacts with TSG101. Interacts with mislocalized cytosolically exposed PRNP; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement.|||Mutant mice have a pleiotropic phenotype that includes the absence of yellow hair pigment, curly hair and whiskers, abnormal craniofacial patterning, reduced embryonic viability due to mispatterning of the left-right body axis and age-dependent spongiform neurodegeneration. Many months before onset of vacuolation, mitochondrial complex IV expression and activity is significantly reduced in mutant brains and oxidative stress is increased. A global reduction of ubiquitinated proteins in the brain is observed. At 1 month of age, null mutant mouse brains have less ubiquitinated TSG101, while adult mutant brains contain more ubiquitinated and insoluble TSG101 than wild type. At 1 month of age, significant increase in EGFR levels in the brains of null mutant mice relative to wild-type mice, suggesting an impaired trafficking to the lysosome for degradation.|||Nucleus|||Partial rescue of the phenotype of mutant null mice.|||Sufficient for normal development, pigmentation and neuronal integrity.|||The RING finger is required for ubiquitin ligase activity.|||Unable to rescue the phenotype of mutant null mice. This sequence has been deduced from the description in PubMed:19422019.|||Widely expressed, with highest levels in brain, heart, kidney and liver. In the CNS, especially prominent in the Purkinje cells of the cerebellum. In the skin, expressed in the basal layer of the epidermis and hair follicles, primarily in the outer root sheath. Isoforms 1, 3, 4 and 5 are equally expressed in the liver. Isoforms 1, 3 and 4 are most abundant in brain, kidney and heart, respectively. http://togogenome.org/gene/10090:Or1j1 ^@ http://purl.uniprot.org/uniprot/Q60879 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Clic1 ^@ http://purl.uniprot.org/uniprot/Q542F1|||http://purl.uniprot.org/uniprot/Q9Z1Q5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chloride channel CLIC family.|||Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions (By similarity).|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity).|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.|||Membrane|||Monomer. Homodimer (in vitro). Interacts with TRAPPC2. Dimerization requires a conformation change that leads to the exposure of a large hydrophobic surface. In vivo, this may lead to membrane insertion. Interacts with AKAP9 (By similarity).|||Nucleus|||Nucleus membrane http://togogenome.org/gene/10090:Qpct ^@ http://purl.uniprot.org/uniprot/A0A0R4J0G6|||http://purl.uniprot.org/uniprot/A0A3B2W7G1|||http://purl.uniprot.org/uniprot/Q3UFN2|||http://purl.uniprot.org/uniprot/Q9CYK2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glutaminyl-peptide cyclotransferase family.|||It is unclear whether this protein requires a metal cofactor for catalysis. It was originally proposed to be a Zn(2+)-dependent metalloenzyme based on structural similarities to bacterial aminopeptidases and the observation that it can bind Zn(2+) ions, typically in a 1:1 stoichiometry (PubMed:21671571). However, a recent study suggests a Zn(2+)-independent catalytic mechanism (By similarity).|||Responsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue (By similarity).|||Secreted http://togogenome.org/gene/10090:Srsf3 ^@ http://purl.uniprot.org/uniprot/P84104 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the splicing factor SR family.|||Cytoplasm|||Highest expression in thymus and pre-B cell lines; high, in testis, brain and spleen; very low in heart and not detectable in liver and kidney.|||Interacts with CPSF6 (By similarity). Interacts with RBMY1A1 (By similarity). Interacts with SREK1/SFRS12 (By similarity). Interacts with NXF1 (By similarity). Interacts with YTHDC1, leading to recruitment to RNA elements adjacent to m6A sites (PubMed:29799838).|||Isoform long is induced by serum; in a tissue culture.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Nucleus speckle|||Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Extensively phosphorylated on serine residues in the RS domain.|||Splicing factor that specifically promotes exon-inclusion during alternative splicing. Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing. Also functions as export adapter involved in mRNA nuclear export. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. Involved in nuclear export of m6A-containing mRNAs via interaction with YTHDC1: interaction with YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export. RNA-binding is semi-sequence specific. http://togogenome.org/gene/10090:Vmn1r191 ^@ http://purl.uniprot.org/uniprot/Q8K4D0 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:H2ab3 ^@ http://purl.uniprot.org/uniprot/S4R1G7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Cwf19l2 ^@ http://purl.uniprot.org/uniprot/Q8BG79 ^@ Similarity ^@ Belongs to the CWF19 family. http://togogenome.org/gene/10090:Tktl1 ^@ http://purl.uniprot.org/uniprot/Q99MX0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transketolase family.|||Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+).|||Binds 1 thiamine pyrophosphate per subunit.|||Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.|||Cytoplasm|||Homodimer.|||Not expressed in the embryonic neocortex. http://togogenome.org/gene/10090:Egr4 ^@ http://purl.uniprot.org/uniprot/Q9WUF2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the EGR C2H2-type zinc-finger protein family.|||Nucleus|||Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCGGGGGCG-3' (GSG). Activates the transcription of target genes whose products are required for mitogenesis and differentiation (By similarity). http://togogenome.org/gene/10090:Shisa4 ^@ http://purl.uniprot.org/uniprot/Q8CA71 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the shisa family.|||Membrane http://togogenome.org/gene/10090:Cnpy2 ^@ http://purl.uniprot.org/uniprot/Q9QXT0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the canopy family.|||Endoplasmic reticulum|||Interacts with MYLIP/MIR.|||Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Or7a35 ^@ http://purl.uniprot.org/uniprot/Q8VGU6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Susd3 ^@ http://purl.uniprot.org/uniprot/Q9D176 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Igf2bp3 ^@ http://purl.uniprot.org/uniprot/Q9CPN8 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All KH domains contribute binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute. The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules.|||Belongs to the RRM IMP/VICKZ family.|||Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Interacts with IGF2BP1. Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1.|||Cytoplasm|||Expressed in oocytes, spermatogonia and spermatocytes (at protein level).|||Expressed in zygotes and blastocysts (at protein level). Expressed in gonads at 12.5 and 14.5 dpc (at protein level). Expressed in germ cells at 16.5 dpc (at protein level). Expressed in brain at 10.5 dpc and declining towards birth (at protein level). Expressed during fetal development at 7, 9.5, 10.5, 12.5, 14.5 and 17.5 dpc and declining towards birth.|||Nucleus|||P-body|||RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (By similarity). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation (By similarity). Binds to beta-actin/ACTB and MYC transcripts (By similarity). Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.|||Stress granule http://togogenome.org/gene/10090:Psmc6 ^@ http://purl.uniprot.org/uniprot/P62334|||http://purl.uniprot.org/uniprot/Q14AQ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC6 and few additional components. Interacts with PAAF1.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC6 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Reg3b ^@ http://purl.uniprot.org/uniprot/P35230 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a hormone in response to different stimuli. Secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways (PubMed:34099862). In pancreas, is able stimulate cell proliferation (PubMed:34099862).|||Bactericidal C-type lectin which acts against several intestinal Gram-positive and Gram-negative bacteria. Lacks antibacterial activity against S.typhimurium. May play a role in protection against infection with S.enteritidis by inhibiting its translocation from the gut lumen into intestinal tissues and further extraintestinal tissues.|||Constitutively expressed in the small intestine, moderately in colon and at an extremely low level in healthy pancreas.|||Forms a hexameric membrane-permeabilizing oligomeric pore on membrane phospholipids. The hexamer is formed by three dimers related by helical symmetry. Forms filaments, filamentation traps pore complexes and limits damage to host cells. Interacts with EXTL3.|||Lipopolysaccharide inhibits pore-forming activity, explaining why is bactericidal for Gram-positive but not Gram-negative bacteria.|||Mice are more susceptible to salmonellosis, but not listeriosis.|||Overexpressed during the acute phase of pancreatitis.|||Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.|||Secreted|||The EPN motif is essential for recognition of the peptidoglycan carbohydrate backbone and for efficient bacterial killing with Glu-114 playing a key role in peptidoglycan binding and bactericidal activity.|||Up-regulated in the intestine by S.typhimurium infection (at protein level). Appears in pancreatic juice after induction of pancreatic inflammation. http://togogenome.org/gene/10090:Mycl ^@ http://purl.uniprot.org/uniprot/P10166|||http://purl.uniprot.org/uniprot/Q3UIE0 ^@ Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX.|||Nucleus http://togogenome.org/gene/10090:Abt1 ^@ http://purl.uniprot.org/uniprot/Q9QYL7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ESF2/ABP1 family.|||Could be a novel TATA-binding protein (TBP) which can function as a basal transcription activator. Can act as a regulator of basal transcription for class II genes.|||Interacts with ESF1/ABTAP. Interacts with IGHMBP2.|||Nucleus|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Lix1l ^@ http://purl.uniprot.org/uniprot/G3X9C8|||http://purl.uniprot.org/uniprot/Q8BQ89 ^@ Similarity ^@ Belongs to the LIX1 family. http://togogenome.org/gene/10090:Or5b111 ^@ http://purl.uniprot.org/uniprot/Q7TQR2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhoq ^@ http://purl.uniprot.org/uniprot/Q8R527 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Cytoplasm|||Interacts with EXO70, CDC42EP1, CDC42EP2 and CDC42EP3 in a GTP-dependent manner (By similarity). Interacts with CDC42EP4, PARD6A, PARD6G (and probably PARD6B) in a GTP-dependent manner. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ). Interacts with GOPC (By similarity). Interacts with ARHGAP33/TCGAP.|||May be post-translationally modified by both palmitoylation and polyisoprenylation.|||Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. May play a role in CFTR trafficking to the plasma membrane. Causes the formation of thin, actin-rich surface projections called filopodia (By similarity).|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. http://togogenome.org/gene/10090:Slc9a9 ^@ http://purl.uniprot.org/uniprot/Q8BZ00 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Deficient mice do not show obvious changes in gross hippocampal morphology or impairments in locomotion, anxiety, smell, or pain sensitivity, however they display autism-like traits, such as reduced ultrasonic vocalization (number of calls and duration), decreased preference for social novelty, and display an increased time self-grooming (PubMed:26755066). Nervous system-specific conditional knockout mice show abnormal social and olfactive behavior, abnormal CNS synaptic transmission, impaired synaptic vesicle exocytosis, impaired presynaptic calcium entry, and decreased synaptic vesicle pH (PubMed:29362376).|||Down-regulated upon bacterial infection in macrophages.|||Early endosome membrane|||Endosomal Na(+), K(+)/H(+) antiporter. Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+) (PubMed:17005858). By facilitating proton efflux, SLC9A9 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Regulates organellar pH and consequently, endosome maturation and endocytic trafficking of plasma membrane receptors and neurotransporters (PubMed:29362376, PubMed:24065030). Promotes the recycling of transferrin receptors back to the cell surface to facilitate additional iron uptake in the brain (By similarity). Regulates synaptic transmission by regulating the luminal pH of axonal endosomes (PubMed:29362376). Regulates phagosome lumenal pH, thus affecting phagosome maturation, and consequently, microbicidal activity in macrophages (PubMed:35716776). Can also be active at the cell surface of specialized cells, e.g., in the inner ear hair bundles uses the high K(+) of the endolymph to regulate intracelular pH (PubMed:17005858).|||Expressed in the brain (PubMed:24065030). Highly expressed in immune cells, specifically macrophages (PubMed:35716776).|||Expression is relatively low during development and begins to increase only postnatally, peaking at around postnatal day 50 and declining thereafter.|||Homodimer; phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) could be involved in the dimer stabilization (By similarity). Interacts (via the C-terminus) with RACK1 (By similarity). Interacts with CHP1 (By similarity).|||Late endosome membrane|||Recycling endosome membrane|||phagosome membrane http://togogenome.org/gene/10090:Kics2 ^@ http://purl.uniprot.org/uniprot/Q6P1I3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose.|||Belongs to the KICS2 family.|||Lysosome membrane|||Part of the KICSTOR complex composed of KPTN, ITFG2, KICS2 and SZT2. SZT2 probably serves as a link between the other three proteins in the KICSTOR complex and may mediate the direct interaction with the GATOR complex via GATOR1. The KICSTOR complex interacts directly with the GATOR1 complex and most probably indirectly with the GATOR2 complex in an amino acid-independent manner. http://togogenome.org/gene/10090:Pdia5 ^@ http://purl.uniprot.org/uniprot/Q921X9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum lumen|||Interacts with CALR (via P-domain). http://togogenome.org/gene/10090:Dnah2 ^@ http://purl.uniprot.org/uniprot/D3Z667 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Vmn1r231 ^@ http://purl.uniprot.org/uniprot/Q8R2A3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Calhm2 ^@ http://purl.uniprot.org/uniprot/Q3V3G1|||http://purl.uniprot.org/uniprot/Q4VA34|||http://purl.uniprot.org/uniprot/Q8VEC4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CALHM family.|||Membrane|||Pore-forming subunit of a voltage-gated ion channel. http://togogenome.org/gene/10090:Gcat ^@ http://purl.uniprot.org/uniprot/E9PWY6|||http://purl.uniprot.org/uniprot/O88986|||http://purl.uniprot.org/uniprot/Q9CZ08 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.|||Mitochondrion|||No visible phenotype.|||Nucleus|||Present in the placenta, brain and liver during embryonic development (at protein level).|||Pyridoxal phosphate (PLP) dependent enzyme, which catalyzes the cleavage of 2-amino-3-oxobutanoate to glycine and acetyl-CoA. Catalyzes the second reaction step on the main metabolic degradation pathway for L-threonine. http://togogenome.org/gene/10090:Tectb ^@ http://purl.uniprot.org/uniprot/O08524 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||May form homomeric filament after self-association or heteromeric filament after association with alpha-tectorin (Probable). Interacts with CEACAM16 (PubMed:25080593).|||One of the major non-collagenous components of the tectorial membrane (By similarity). The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals.|||The presence of a hydrophobic C-terminus preceded by a potential cleavage site strongly suggests that tectorins are synthesized as glycosylphosphatidylinositol-linked, membrane-bound precursors. Tectorins are targeted to the apical surface of the inner ear epithelia by the lipid and proteolytically released into the extracellular compartment.|||Zona pellucida domain may enable to form filaments.|||extracellular matrix http://togogenome.org/gene/10090:Tcf15 ^@ http://purl.uniprot.org/uniprot/Q60756 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early transcription factor that plays a key role in somitogenesis, paraxial mesoderm development and regulation of stem cell pluripotency (PubMed:7597044, PubMed:8955271, PubMed:23395635, PubMed:32669716, PubMed:24038871). Essential for the mesenchymal to epithelial transition associated with somite formation (PubMed:7597044, PubMed:8955271, PubMed:24038871). Required for somite morphogenesis, thereby regulating patterning of the axial skeleton and skeletal muscles (PubMed:8955271). Required for proper localization of somite epithelium markers during the mesenchymal to epithelial transition (PubMed:24038871). Also plays a key role in regulation of stem cell pluripotency (PubMed:23395635, PubMed:32669716). Promotes pluripotency exit of embryonic stem cells (ESCs) by priming ESCs for differentiation (PubMed:23395635). Acts as a key regulator of self-renewal of hematopoietic stem cells (HSCs) by mediating HSCs quiescence and long-term self-renewal (PubMed:32669716). Together with MEOX2, regulates transcription in heart endothelial cells to regulate fatty acid transport across heart endothelial cells (PubMed:25561514). Acts by forming a heterodimer with another helix-loop-helix (bHLH) protein, such as TCF3/E12, that binds DNA on E-box motifs (5'-CANNTG-3') and activates transcription of target genes (PubMed:15226298, PubMed:23395635).|||Expressed in heart and skeletal muscle (PubMed:8041747, PubMed:7597044). Specifically expressed in a subpopulation of embryonic stem cells (ESCs), that are still undifferentiated but primed for ifferentiation (PubMed:23395635). Expressed in hematopoietic stem cells (HSCs) (PubMed:32669716).|||Expressed in the embryonic day 4.5 embryo (PubMed:23395635). Expressed in paraxial mesoderm and developing somites (PubMed:7729571). At 7.5 dpc, low expression is detected in a subdomain of the primitive mesoderm (PubMed:8041747). At 8.5 dpc, expressed at high levels throughout the uncompartmentalized epithelial somites and in the rostral paraxial mesoderm (PubMed:8041747). By 9.5 dpc, expression is confined to the somite and is most prominent in the myotome and dermatome (PubMed:8041747). At 10 dpc, expression in somite declines in the myotome but persists at high level in the dermatome (PubMed:8041747). At 10.5 dpc, expression is seen only in the somites in the caudal portion of the embryo (PubMed:8041747).|||Heterodimer; efficient DNA binding requires dimerization with another bHLH protein, such as TCF3/E12 (PubMed:15226298, PubMed:23395635). Interacts with MEOX2 (PubMed:25561514).|||Lethality within an hour of birth, possibly caused by rib defects that lead to respiratory distress (PubMed:8955271). At birth, neonates display obvious caudal agenesis with tails that are shortened and curled (PubMed:8955271). They also lack the normal cervical flexure of the vertebral column, and their hindlimbs are curved towards the midline (PubMed:8955271). Neonates also display low-set ears, a thickened neck and loose skin (PubMed:8955271). Defects are caused by impaired formation of somites: cells from the paraxial mesoderm are unable to form epithelia, preventing formation of somites (PubMed:8955271). In the absence of normal somites, the axial skeleton and skeletal muscle form but are improperly patterned (PubMed:8955271). Hematopoietic stem cells (HSCs) show a specific loss of quiescent stem cells (PubMed:32669716).|||Nucleus http://togogenome.org/gene/10090:Or52n3 ^@ http://purl.uniprot.org/uniprot/Q8VG79 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or6s1 ^@ http://purl.uniprot.org/uniprot/E9Q0Z1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or8d2b ^@ http://purl.uniprot.org/uniprot/Q9EQ98 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krt13 ^@ http://purl.uniprot.org/uniprot/P08730 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the oral mucosa, including the palate, dorsal tongue, ventral tongue, and the floor of the mouth at 17.5 dpc (PubMed:32758484). Expressed in basal cells and differentiated keratinocytes at the ventral surface and the oral interpapillary cell column on the dorsal surface of the tongue at birth (PubMed:32758484). Ubiquitously expressed in basal cells and differentiated keratinocytes on the ventral tongue epithelium, however expression was limited to the cells in the interpapillary region and keratinized layer on the dorsal tongue at postnatal day 20 (P20) (PubMed:32758484). Also expressed in the buccal mucosa and esophagus at P20 (PubMed:32758484).|||Expressed in tongue epithelia (at protein level) (PubMed:1695590). Expressed in upper suprabasal layers of the corneal epithelium (at protein level) (PubMed:26758872).|||Heterotetramer of two type I and two type II keratins.|||Knockout mice maintain a normal body weight and developmental phenotype (PubMed:32758484). Tongue histological abnormalities are evident at P20 including the loss of two lingual vessel branches at the ventral side of the tongue which appears white and wrinkled, especially on the ventral surface at three weeks of age (PubMed:32758484). Loss of column-like basal cell organization and increase in nuclear atypia and vacuolization in both the basal and suprabasal layers of the tongue (PubMed:32758484). Loss of keratohyalin granules, abnormal presence of cuboidal cells in the suprabasal layers and loss of organization of the outermost keratin layer leading to a foamy appearance (PubMed:32758484). Increase in intracellular gaps, however desmosomes still formed but were found broken and intermediate filaments running from the desmosomes to the cytoplasm were missing or reduced (PubMed:32758484). Cytoplasmic vacuolization is evident in all cell layers and large lipid droplets are found in granular cells in the tongue epithelia (PubMed:32758484). Severe abnormalities in buccal mucosa and esophagus including thickened epithelium, immature suprabasal cells, loss of keratohyalin granules and a disorganized keratin layer at P20 (PubMed:32758484). Disrupted proliferation and differentiation in tongue epithelial cells at P20, as indicated by disordered expression of the transcription factor Tp63/P63, the basal progenitor cell marker Krt5, and the differentiated epithelial cell marker Loricrin (PubMed:32758484). Increase in proliferating cells in the upper layers of the tongue epithelium at P20 (PubMed:32758484). Normal tongue morphology, structural architecture and epithelial cell proliferation at birth (PubMed:32758484). Differential expression of 125 genes in the tongue at P0, enriched in keratinization, proinflammatory responses, stress-activated protein kinase signaling and threonine/lipid metabolic processes (PubMed:32758484). Differential expression of 2907 genes in the ventral tongue at P20 involved in a range of processes, however primarily in cell cycle regulatory pathways (PubMed:32758484). Increase in the expression of CCNE1 and CCNE2 in response to in vitro mechanical stress of the tongue (PubMed:32758484).|||O-glycosylated; glycans consist of single N-acetylglucosamine residues.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||Type 1 keratin (Probable). Maintains postnatal tongue mucosal cell homeostasis and tissue organization in response to mechanical stress, potentially via regulation of the G1/S phase cyclins CCNE1 and CCNE2 (PubMed:32758484). http://togogenome.org/gene/10090:Aff3 ^@ http://purl.uniprot.org/uniprot/D3YYI6 ^@ Similarity ^@ Belongs to the AF4 family. http://togogenome.org/gene/10090:Arhgap12 ^@ http://purl.uniprot.org/uniprot/Q8C0D4 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Irf1 ^@ http://purl.uniprot.org/uniprot/P15314|||http://purl.uniprot.org/uniprot/Q3U5M1|||http://purl.uniprot.org/uniprot/Q5SX13 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by MYD88.|||Belongs to the IRF family.|||Cytoplasm|||Induced by IFN-gamma (PubMed:17018642, PubMed:18955028, PubMed:29321274). Induced by influenza A virus (PubMed:29321274).|||Monomer (PubMed:9422515). Homodimer (PubMed:9422515). Interacts with EP300 (By similarity). Interacts with MYD88 (PubMed:17018642). Interacts with PIAS3 (PubMed:12387893).|||Nucleus|||Phosphorylated by CK2 and this positively regulates its activity.|||Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation (PubMed:12387893, PubMed:18955028). Sumolyated by UBE2I/UBC9 and SUMO1 (PubMed:18955028). Inactivates the tumor suppressor activity (By similarity). Elevated levels in tumor cells (By similarity). Major site is Lys-276 (By similarity). Sumoylation is enhanced by PIAS3 (PubMed:12387893). Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (By similarity).|||Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431, PubMed:25774715). Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431). Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431). Binds to a consensus sequence in gene promoters (By similarity). Its target genes for transcriptional activation activity are: genes involved in anti-viral response, such as IFN-alpha/beta, RIGI, TNFSF10/TRAIL, ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as GBP2, GBP5, IRGB10 and NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1/IRG1 (PubMed:12387893, PubMed:17018642, PubMed:18955028, PubMed:21909274, PubMed:20308629, PubMed:25774715, PubMed:27693356, PubMed:29321274, PubMed:30635240). Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4 (PubMed:18641303). Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53 (By similarity). Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431). Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431). Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells (PubMed:11244049, PubMed:11846971, PubMed:11846974, PubMed:16932750, PubMed:20049431).|||Ubiquitinated. Appears to compete with sumoylation on C-terminal sites (By similarity). http://togogenome.org/gene/10090:Celf6 ^@ http://purl.uniprot.org/uniprot/Q7TN33 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CELF/BRUNOL family.|||Cytoplasm|||Nucleus|||RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of TNNT2 in a muscle-specific splicing enhancer (MSE)-dependent manner. Promotes also exon exclusion of INSR pre-mRNA (By similarity). http://togogenome.org/gene/10090:Lmo4 ^@ http://purl.uniprot.org/uniprot/P61969 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subunit|||Tissue Specificity ^@ Expressed in a wide variety of tissues.|||Expressed in the developing spinal cord in the ventricular zone and down-regulated in the lateral zone at 11.5 dpc (at protein level) (PubMed:18539116). Highly expressed in motor neurons that emerge from the ventricular zone at 11.5 dpc (at protein level) (PubMed:18539116). At 12.5 dpc, highly expressed in motor neurons in medial median motor column (MMCm), which innervate dorsal axial muscles (PubMed:18539116).|||Interacts strongly with LDBS (PubMed:9860983, PubMed:12727888, PubMed:15343268, PubMed:17001033, PubMed:18539116). Interacts with LDB2 and LDB1 (PubMed:9860983, PubMed:12727888, PubMed:15343268, PubMed:17001033, PubMed:18539116, PubMed:23353824). Interaction with complexes consisting of at least LDB1 and LHX3 acts to disassemble the complex; may preferentially disassemble LDB1-LHX3 complexes rather than complexes consisting of LDB1, LHX3 and ISL1 (PubMed:18539116). Interacts (via the LIM zinc-binding domain 1) with RBBP8 (PubMed:11751867, PubMed:23353824). Interacts with both RPPB8 and LDB1 through the same face and cannot bind to both proteins simultaneously (PubMed:23353824). Interacts with BRCA1 (via the BRCT domains); the interaction represses BRCA1 transcriptional activity (PubMed:11751867). Interacts with DEAF1; LMO4 blocks export from nucleus (PubMed:22723967).|||Overall patterning of ventral spinal cord neurons is normal at 12.5 dpc and 14.5 dpc, but there are additional ectopic V2 interneurons (V2-INs) at all axial levels of the spinal cord; phenotype exacerbated in an MNX1 mutant background (PubMed:18539116). In an MNX1 mutant background, genes typically expressed in V2-INs expressed ectopically in motor neurons (MNs) (PubMed:18539116). Abnormal guidance of motor axons in an MNX1 mutant background (PubMed:18539116).|||Transcription cofactor (PubMed:18539116). Plays a role in establishing motor neuron identity, in concert with MNX1, acting, at least in part, to disrupt LDB1-LHX3 complexes thereby negatively modulating interneuron genes in motor neurons (PubMed:18539116). http://togogenome.org/gene/10090:Gdf6 ^@ http://purl.uniprot.org/uniprot/A2AII0|||http://purl.uniprot.org/uniprot/P43028 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Expressed in different subsets of developing joints. Highly expressed in the cochlea (PubMed:32369452).|||Growth factor that controls proliferation and cellular differentiation in the retina and bone formation. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map (PubMed:23307924). Required for normal formation of bones and joints in the limbs, skull, digits and axial skeleton. Plays a key role in establishing boundaries between skeletal elements during development. Regulation of GDF6 expression seems to be a mechanism for evolving species-specific changes in skeletal structures (PubMed:26774823). Seems to positively regulate differentiation of chondrogenic tissue through the growth factor receptors subunits BMPR1A, BMPR1B, BMPR2 and ACVR2A, leading to the activation of SMAD1-SMAD5-SMAD8 complex. The regulation of chondrogenic differentiation is inhibited by NOG (PubMed:12606286, PubMed:16049014). Also involved in the induction of adipogenesis from mesenchymal stem cells. This mechanism acts through the growth factor receptors subunits BMPR1A, BMPR2 and ACVR2A and the activation of SMAD1-SMAD5-SMAD8 complex and MAPK14/p38 (PubMed:23527555).|||Homodimer; disulfide-linked.|||Mice lacking GDF6 display photoreceptor degeneration. Animals exhibit abnormal electroretinograms with up to 66% decreases in the bipolar cell-driven b-wave and 54% decreases in the photoreceptor-mediated a-wave amplitudes, as well as 3 to 27% reduced photopic flicker fusion. The lengths, but not the widths, of dermal flat bones in the skull and the digits are significantly shorter than in wild type (PubMed:26774823). GDF6-knockout mice also shows cochlear aplasia, while the vestibular anatomy is normal (PubMed:32369452).|||Secreted|||Strongly up-regulated in tibialis anterior muscles after denervation. http://togogenome.org/gene/10090:Chrna7 ^@ http://purl.uniprot.org/uniprot/P49582|||http://purl.uniprot.org/uniprot/Q53YJ9|||http://purl.uniprot.org/uniprot/Q8CC01 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-7/CHRNA7 sub-subfamily.|||Cell membrane|||Glycosylations at Asn-46, Asn-90 and Asn-133 are essential for TMEM35A/NACHO-mediated proper subunit assembly and trafficking to the cell membrane.|||Homopentamer (PubMed:32783947). Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6. Interacts with the alpha-conotoxin RgIA (By similarity). Interacts with alpha-conotoxins ImI and ImII (By similarity). Interacts with CANX (By similarity).|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Sele ^@ http://purl.uniprot.org/uniprot/Q00690|||http://purl.uniprot.org/uniprot/Q3U5F6 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the selectin/LECAM family.|||Cell membrane|||Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1 (PubMed:1375914). May have a role in capillary morphogenesis.|||Interacts with SELPLG/PSGL1 and PODXL2 through the sialyl Lewis X epitope. SELPLG sulfation appears not to be required for this interaction.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Tmem171 ^@ http://purl.uniprot.org/uniprot/Q4KL18 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tert ^@ http://purl.uniprot.org/uniprot/O70372 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the reverse transcriptase family. Telomerase subfamily.|||Catalytic component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. The molecular chaperone HSP90/P23 complex is required for correct assembly and stabilization of the active telomerase. Interacts directly with HSP90A and PTGES3. Interacts with HSPA1A; the interaction occurs in the absence of TERC and dissociates once the complex has formed. Interacts with RAN; the interaction promotes nuclear export of TERT. Interacts with XPO1. Interacts with PTPN11; the interaction retains TERT in the nucleus. Interacts with NCL (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar localization of TERT (By similarity). Interacts with SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated signaling (PubMed:19571879). Interacts with MCRS1 (isoform MCRS2); the interaction inhibits in vitro telomerase activity (By similarity). Interacts with PIF1; the interaction has no effect on the elongation activity of TERT (PubMed:17130244). Interacts with PML; the interaction recruits TERT to PML bodies and inhibits telomerase activity (By similarity). Interacts with GNL3L (PubMed:19487455). Interacts with isoform 1 and isoform 2 of NVL (By similarity). Interacts with DHX36 (By similarity). Interacts with ATF7 (By similarity).|||Cytoplasm|||High activity in intestine, liver and testis, moderate in lung, very low in muscle, heart and brain.|||Highest levels in midgestational stages, 9.5 dpc to 15.5 dpc.|||Nucleus|||PML body|||Phosphorylation at Tyr-697 under oxidative stress leads to translocation of TERT to the cytoplasm and reduces its antiapoptotic activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention. Phosphorylation by the AKT pathway promotes nuclear location. Phosphorylation at the G2/M phase at Ser-447 by DYRK2 promotes ubiquitination by the EDVP complex and degradation (By similarity).|||Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis (By similarity).|||The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity (By similarity).|||The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA synthesis.|||The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers.|||Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-447 by DYRK2. Ubiquitinated leads to proteasomal degradation (By similarity).|||Was originally thought to originate from rat.|||nucleolus|||nucleoplasm|||telomere http://togogenome.org/gene/10090:Rhox3e ^@ http://purl.uniprot.org/uniprot/Q4TU90 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Tedc2 ^@ http://purl.uniprot.org/uniprot/Q6GQV0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a positive regulator of ciliary hedgehog signaling. Required for centriole stability.|||Interacts with TEDC1 (PubMed:29459677). Found in a complex with TEDC1, TEDC2, TUBE1 and TUBD1 (PubMed:29459677).|||centriole|||cilium http://togogenome.org/gene/10090:Lingo1 ^@ http://purl.uniprot.org/uniprot/Q9D1T0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed broadly at high levels in the whole embryo and becomes progressively restricted to the central nervous system by 14.5 dpc. Extensively expressed across the central nervous system through late embryogenesis and during postnatal development, with a peak of expression around the first week after birth.|||Functional component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. Is also an important negative regulator of oligodentrocyte differentiation and axonal myelination (By similarity). Acts in conjunction with RTN4 and RTN4R in regulating neuronal precursor cell motility during cortical development.|||Highly specific expression in the central nervous system. Predominant expression in neocortex, amygdala, hippocampus, thalamus and entorhinal cortex, with lower levels in cerebellum and basal nuclei.|||Homotetramer. Forms a ternary complex with RTN4R/NGFR and RTN4R/TNFRSF19 (By similarity). Interacts with NGRF and MYT1L (PubMed:18186492). Interacts with RTN4R (PubMed:18186492, PubMed:22923615).|||In mice lacking Lingo1 and MPTP-intoxicated, a model for Parkinson disease, the dopaminergic neurons survival is increased and behavioral abnormalities reduced.|||N-glycosylated. Contains predominantly high-mannose glycans (By similarity).|||The intracellular domain of LINGO1 interacts with MYT1L.|||Up-regulated in brain from MPTP-intoxicated mice, a model for Parkinson disease. http://togogenome.org/gene/10090:Gltpd2 ^@ http://purl.uniprot.org/uniprot/Q8K0R6 ^@ Similarity ^@ Belongs to the GLTP family. http://togogenome.org/gene/10090:Olr1 ^@ http://purl.uniprot.org/uniprot/Q9EQ09 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Homodimer; disulfide-linked. May form a hexamer composed of 3 homodimers. Interacts with HSP70 (By similarity).|||Membrane raft|||N-glycosylated.|||Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that induces vascular endothelial cell activation and dysfunction, resulting in pro-inflammatory responses, pro-oxidative conditions and apoptosis. Its association with oxLDL induces the activation of NF-kappa-B through an increased production of intracellular reactive oxygen and a variety of pro-atherogenic cellular responses including a reduction of nitric oxide (NO) release, monocyte adhesion and apoptosis. In addition to binding oxLDL, it acts as a receptor for the HSP70 protein involved in antigen cross-presentation to naive T-cells in dendritic cells, thereby participating in cell-mediated antigen cross-presentation. Also involved in inflammatory process, by acting as a leukocyte-adhesion molecule at the vascular interface in endotoxin-induced inflammation. Also acts as a receptor for advanced glycation end (AGE) products, activated platelets, monocytes, apoptotic cells and both Gram-negative and Gram-positive bacteria (By similarity).|||Secreted|||The C-type lectin domain mediates the recognition and binding of oxLDL.|||The Neck region contains 3 internal repeats that are only found in rodents.|||The cytoplasmic region is required for subcellular sorting on the cell surface. http://togogenome.org/gene/10090:Ciao2a ^@ http://purl.uniprot.org/uniprot/Q9DCL2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MIP18 family.|||Component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins (PubMed:23891004). As a CIA complex component and in collaboration with CIAO1 specifically matures ACO1 and stabilizes IREB2 (PubMed:23891004). May play a role in chromosome segregation through establishment of sister chromatid cohesion. May induce apoptosis in collaboration with APAF1 (PubMed:25716227).|||Cytoplasm|||Expressed in interstitial cell lineages.|||Monomer and homodimer (By similarity). Component of the CIA complex (PubMed:23891004). Interacts with CIAO1 (PubMed:23891004). Interacts with IREB2 (PubMed:23891004). Interacts with APAF1 (By similarity). http://togogenome.org/gene/10090:Sema4f ^@ http://purl.uniprot.org/uniprot/Q9Z123 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell membrane|||During 14 dpc expression is abundant in the cerebral cortex, hippocampus, brain stem and the mitral and glomerular layers of the olfactory bulb, expression in the olfactory bulb remains evident into adulthood (at protein level) (PubMed:21945643). Expressed in proliferative layers and oligodendroglial precursor cells (OPCs) during embryonic development (14-16 dpc), in regions such as the ganglionic eminence, mamillothalamic tract, neuroepithelium, and cortical plate (at protein level) (PubMed:21945643). Expressed in migrating OPCs along the optic nerve at 16.5 dpc (at protein level) (PubMed:21945643). During late embryonic development (18 dpc) expression is abundant in pyramidal and granular cells of the hippocampus, and OPCs in the migratory pathway and embryonic fimbria of the hippocampus (at protein level) (PubMed:21945643). At postnatal day 1 (P1) expression is abundant in the corpus callosum, anterior commissure, and several nerve nuclei in the hindbrain, such as the oculomotor nucleus, the periaqueductal gray area, the facial nucleus, the colliculli, and the raphe and pararubral nuclei, as well as in the proliferative layers of the anterior subventricular zone, with expression remaining evident into adulthood (at protein level) (PubMed:21945643). A significant abundance of protein is apparent in the arcuate and posterior hypothalamic nuclei at P10, and additionally in hypothalamic OPCs, expression becomes evident in the arcuate nucleus at P15 (at protein level) (PubMed:21945643). Abundant expression throughout the embryonic brain from 14 dpc onwards with decreased expression in all areas of the brain in adulthood, however expression remains relatively abundant (PubMed:21945643).|||Expressed throughout the adult brain, where it shows particularly strong expression in the hippocampus, corpus callosum, granular layer and deep nuclei of the cerebellum, and the mitral layer of the olfactory bulb (at protein level) (PubMed:21945643). At the cellular level, detected in neuronal precursors, postmitotic neurons, pyramidal neurons, and glial cells including mature oligodendocytes and oligodendroglial precursor cells (at protein level) (PubMed:21945643).|||Interacts (via PDZ-binding motif) with DLG4/SAP90 (via PDZ domain 2); this interaction may promote translocation of DLG4/SAP90 to the membrane.|||Perikaryon|||Postsynaptic density|||Probable cell surface receptor that regulates oligodendroglial precursor cell migration (PubMed:21945643). Might also regulate differentiation of oligodendroglial precursor cells (By similarity). Has growth cone collapse activity against retinal ganglion-cell axons (By similarity).|||dendrite http://togogenome.org/gene/10090:Ccdc14 ^@ http://purl.uniprot.org/uniprot/Q8K2J4 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence.|||Interacts with CEP63.|||Negatively regulates centriole duplication. Negatively regulates CEP63 and CDK2 centrosomal localization.|||centriolar satellite http://togogenome.org/gene/10090:Accsl ^@ http://purl.uniprot.org/uniprot/Q3UX83 ^@ Caution|||Similarity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||While belonging to the class-I pyridoxal-phosphate-dependent aminotransferase family, it lacks a number of residues which are necessary for activity thus suggesting that it lacks enzymatic activity. http://togogenome.org/gene/10090:Mptx1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J077|||http://purl.uniprot.org/uniprot/Q8R1M8 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pentraxin family.|||Binds 2 calcium ions per subunit.|||Expressed in colon.|||Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.|||Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits (By similarity).|||Secreted http://togogenome.org/gene/10090:Rbbp6 ^@ http://purl.uniprot.org/uniprot/P97868 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Contains a N-terminus DWNN domain, a zinc-finger domain and a C4C4 zinc-binding RING finger domain (By similarity). The ring finger may indeed be a U-box domain (By similarity).|||E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome (By similarity). May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth retardation (PubMed:17470788). Regulates DNA-replication and common fragile sites (CFS) stability in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication (PubMed:24726359).|||Early embryonic lethality before 7.5 dpc, accompanied by accumulation of p53 and widespread apoptosis.|||Expression is reduced during terminal differentiation. Expression is induced in the G2/M phase of the cell cycle (at protein level).|||Highly expressed in testis. Expressed at lower levels in brain, heart, kidney, liver, lung, skeletal muscle, spleen, thymus and tongue.|||Interacts with MDM2 and YBX1 (By similarity). Interacts also with p53/TP53 and RB1. Interacts with NEK6 (By similarity). Interacts with ZBTB38 (By similarity).|||Phosphorylated by NEK6.|||centrosome|||nucleolus http://togogenome.org/gene/10090:Nectin1 ^@ http://purl.uniprot.org/uniprot/Q9JKF6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nectin family.|||Cell membrane|||Cis- and trans-homodimer. Can form trans-heterodimers with NECTIN3. Interaction between NECTIN1 and NECTIN3 on the pre- and postsynaptic sites, respectively, initiates the formation of puncta adherentia junctions between axons and dendrites. Interacts (via Ig-like C2-type domain 2) with FGFR1, FGFR2 and FGFR3. Interacts (via Cytoplasmic domain) with AFDN, providing a connection with the actin cytoskeleton. Interacts with HSV glycoprotein D (gD).|||Ig-like C2-type 2 mediates neurite outgrowth through binding, induction of phosphorylation, and activation of FGFR.|||Involved in cell adhesion and synaptogegesis. Has some neurite outgrowth-promoting activity. Receptor for alphaherpesvirus (HSV-1, HSV-2 and pseudorabies virus) entry into cells.|||Presynaptic cell membrane http://togogenome.org/gene/10090:Rbx1 ^@ http://purl.uniprot.org/uniprot/P62878 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RING-box family.|||E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair (PubMed:22118460, PubMed:33590678). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (By similarity). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components (By similarity). As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation (By similarity). Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme, like CDC34, to the complex and brings it into close proximity to the substrate (By similarity). Probably also stimulates CDC34 autoubiquitination (By similarity). May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair (By similarity). Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M (By similarity). Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (By similarity). In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM (By similarity). As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (By similarity).|||Expressed at high levels in zygotes and at lower levels in germinal vesicle (GV) stage oocytes and MII-stage oocytes. Expression strongly decreases from 2-cell stage to blastula.|||Interacts with COPS6. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B (PubMed:22118460). Interacts with CAND1 (PubMed:22118460). Interacts with UBE2M (By similarity). Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2. Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL. Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II (By similarity). Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1. Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), SOCS1 or WSB1 and CUL5. Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (By similarity). Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7. Interacts with CDC34. Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3. Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34 (By similarity). Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein. Part of the BCR(ENC1) complex containing ENC1. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KLHL41) complex containing KLHL41. Part of the BCR(KEAP1) complex containing KEAP1 (By similarity). Interacts with SESN1 and SESN2 (By similarity). Interacts with NOTCH2 (By similarity). Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (By similarity). Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (By similarity). Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (By similarity). Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:33590678).|||The RING-type zinc finger domain is essential for ubiquitin ligase activity (By similarity). It coordinates an additional third zinc ion (PubMed:22118460).|||Widely expressed (PubMed:10643962). Expressed in oocytes (at protein level) (PubMed:24357321). http://togogenome.org/gene/10090:Rpl13 ^@ http://purl.uniprot.org/uniprot/P47963|||http://purl.uniprot.org/uniprot/Q5RKP3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL13 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Vmn1r89 ^@ http://purl.uniprot.org/uniprot/Q8R256 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Glcci1 ^@ http://purl.uniprot.org/uniprot/Q8K3I9 ^@ Tissue Specificity ^@ Predominantly expressed in thymus and testis, especially in CD4+CD8+ cells and at specific stages of spermatogenesis. http://togogenome.org/gene/10090:Nacc2 ^@ http://purl.uniprot.org/uniprot/Q9DCM7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Functions as a transcriptional repressor through its association with the NuRD complex. Recruits the NuRD complex to the promoter of MDM2, leading to the repression of MDM2 transcription and subsequent stability of p53/TP53 (By similarity).|||Homooligomer; mediated by the BTB domain. Interacts with the NuRD complex. Interacts (via C-terminal part) with HDAC2. Interacts (via BTB domain) with MTA1, MTA2 and MTA3.|||Nucleus http://togogenome.org/gene/10090:Urod ^@ http://purl.uniprot.org/uniprot/P70697 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the uroporphyrinogen decarboxylase family.|||Catalyzes the sequential decarboxylation of the four acetate side chains of uroporphyrinogen to form coproporphyrinogen and participates in the fifth step in the heme biosynthetic pathway. Isomer I or isomer III of uroporphyrinogen may serve as substrate, but only coproporphyrinogen III can ultimately be converted to heme (By similarity). In vitro also decarboxylates pentacarboxylate porphyrinogen I (PubMed:8661721).|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Tspyl5 ^@ http://purl.uniprot.org/uniprot/Q69ZB3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the nucleosome assembly protein (NAP) family.|||Interacts with USP7.|||Involved in modulation of cell growth and cellular response to gamma radiation probably via regulation of the Akt signaling pathway. Involved in regulation of p53/TP53. Suppresses p53/TP53 protein levels and promotes its ubiquitination; the function is dependent on USP7 and independent on MDM2. Proposed to displace p53/TP53 from interaction with USP7 (By similarity). http://togogenome.org/gene/10090:Atp5j2 ^@ http://purl.uniprot.org/uniprot/P56135 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase F chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Hmga1b ^@ http://purl.uniprot.org/uniprot/P17095|||http://purl.uniprot.org/uniprot/Q3TVP0|||http://purl.uniprot.org/uniprot/Q566K0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HMGA family.|||Chromosome|||HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions.|||Interacts with HIPK2.|||Isoforms HMG-I and HMG-Y can be phosphorylated by HIPK2. Phosphorylation may modulate DNA-binding affinity (By similarity).|||Methylation at Arg-58 is mutually exclusive with methylation at Arg-60.|||Nucleus http://togogenome.org/gene/10090:Tspan12 ^@ http://purl.uniprot.org/uniprot/Q8BKT6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Expressed in the neonatal retinal vasculature but not other retinal tissues. Also detected in the neonatal meningeal vasculature and in nonvascular cell types, such as the smooth muscle cells in the neonatal intestine.|||Interacts (when palmitoylated) with ADAM10. Interacts with MMP14/MT1-MMP (By similarity). Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP).|||Mice are viable and fertile but display defects in retinal vascularization. In retinas between P5 and P12, the centrifugal outgrowth of the nerve fiber layer (NFL) vasculature is moderately delayed in retinas. At P11, vertical sprouts and plexiform layer (OPL) capillaries appear in wild-type mice, whereas both are completely absent in mutant mice. In adult mutant mice, the plexiform layer (OPL) remains avascular, confirming that the defect is not transient. The thickness of the outer nuclear layer in retinas is consistently reduced in adult mutant but not neonatal mice, indicating that neural cells are secondarily affected by the vascular defects.|||Palmitoylated; required for interaction with ADAM10.|||Regulator of cell surface receptor signal transduction. Acts as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity (By similarity). Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activate the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). http://togogenome.org/gene/10090:Eif4e3 ^@ http://purl.uniprot.org/uniprot/Q9DBB5 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic initiation factor 4E family.|||Only expressed in heart, skeletal muscle, lung and spleen.|||Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis. May act as an inhibitor of EIF4E1 activity.|||eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least eIF4A, eIF4E and eIF4G (By similarity). EIF4E3 interacts with EIF4G1, but not with EIF4EBP1, EIF4EBP2 and EIF4EBP3. http://togogenome.org/gene/10090:Clic3 ^@ http://purl.uniprot.org/uniprot/Q9D7P7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with the C-terminal of MAPK15.|||Belongs to the chloride channel CLIC family.|||Can insert into membranes and form chloride ion channels. May participate in cellular growth control (By similarity).|||Cytoplasm|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity).|||Membrane|||Nucleus http://togogenome.org/gene/10090:Mrgprb3 ^@ http://purl.uniprot.org/uniprot/Q91ZC1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Membrane|||Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Arfgef2 ^@ http://purl.uniprot.org/uniprot/A2A5R2 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Cytoplasmic vesicle|||Endosome|||Golgi apparatus|||Homodimer. Interacts with ARFGEF1/BIG1; both proteins are probably part of the same or very similar macromolecular complexes. Interacts with PRKAR1A, PRKAR2A, PRKAR1B, PRKAR2B, PPP1CC, PDE3A, TNFRSF1A, MYCBP and EXOC7. Interacts with GABRB1, GABRB2 and GABRB3 (By similarity).|||In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1.|||Inhibited by brefeldin A.|||Membrane|||Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways (By similarity).|||Synapse|||centrosome|||cytoskeleton|||dendrite|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Rbks ^@ http://purl.uniprot.org/uniprot/Q8R1Q9 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity. Competitively inhibited by phosphonoacetic acid, etidronate, 2-carboxethylphosphonic acid, N-(phosphonomethyl)glycine, N-(phosphonomethyl)iminodiacetic acid and clodronate (By similarity).|||Belongs to the carbohydrate kinase PfkB family. Ribokinase subfamily.|||Catalyzes the phosphorylation of ribose at O-5 in a reaction requiring ATP and magnesium. The resulting D-ribose-5-phosphate can then be used either for sythesis of nucleotides, histidine, and tryptophan, or as a component of the pentose phosphate pathway.|||Cytoplasm|||Homodimer.|||Nucleus|||Requires a divalent cation, most likely magnesium in vivo, as an electrophilic catalyst to aid phosphoryl group transfer. It is the chelate of the metal and the nucleotide that is the actual substrate. http://togogenome.org/gene/10090:Arid5a ^@ http://purl.uniprot.org/uniprot/D3Z0W0|||http://purl.uniprot.org/uniprot/Q3U108 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ DNA-binding protein that may regulate transcription and act as a repressor by binding to AT-rich stretches in the promoter region of target genes (By similarity). May positively regulate chondrocyte-specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention (PubMed:21346191). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (By similarity). As RNA-binding protein involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as IL6, STAT3 and TBX21. Binds to stem loop structures located in the 3'UTRs of IL6, STAT3 and TBX21 mRNAs; at least for STAT3 prevents binding of ZC3H12A to the mRNA stem loop structure thus inhibiting its degradation activity. Contributes to elevated IL6 levels possibly implicated in autoimmunity processes. IL6-dependent stabilization of STAT3 mRNA may promote differentiation of naive CD4+ T-cells into T-helper Th17 cells (PubMed:23676272, PubMed:27022145). In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling (PubMed:24782182). Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (PubMed:27671645). Stabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR; thereby competing with the mRNA-destabilizing functions of RC3H1 and endoribonuclease ZC3H12A (PubMed:29244194).|||Expressed in T cells (at protein level) (PubMed:29244194). Expressed at high levels in cartilage, heart, testis and bone (PubMed:21346191).|||In macrophages by LPS, IL1B and IL6 (PubMed:21346191). By IL6/STAT3 signaling in T-helper Th17 cells (PubMed:24782182, PubMed:29244194).|||Interacts with SOX9 (PubMed:21346191). Interacts with ESR1 (By similarity). Interacts with RORC (PubMed:24782182).|||Mice are resistant to experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune model (PubMed:29244194). The expression of pro-inflammatory mediators is severely reduced in EAE (PubMed:29244194).|||Nucleus|||Phosphorylated by MAPK14 on serine residues involving a TLR4 signaling pathway upon lipopolysaccharide (LPS) stimulation leading to its ubiquitination and proteasomal degradation.|||Ubiquitinated leading to proteasomal degradation; involving WWP1 linked to MAPK14-mediated phosphorylation upon LPS stimulation. http://togogenome.org/gene/10090:Or5ac23 ^@ http://purl.uniprot.org/uniprot/Q7TS37 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mcm3ap ^@ http://purl.uniprot.org/uniprot/Q9WUU9 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (By similarity). Through the acetylation of histones, affects the assembly of nucleosomes at immunoglobulin variable region genes and promotes the recruitment and positioning of transcription complex to favor DNA cytosine deaminase AICDA/AID targeting, hence promoting somatic hypermutations (PubMed:23652018).|||Belongs to the SAC3 family.|||Chromosome|||Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY (By similarity). Interacts with RNA polymerase II subunit POLR2A and with the transcription elongation factor SUPT5H/SPT5 (By similarity). Interacts (via FG-repeats) with NXF1; this interaction is not mediated by RNA (By similarity). Interacts with nuclear envelope proteins NUP62, NUP153 and RANBP2/NUP358; interaction with NUP153 is required for full localization at the nuclear pore complex (By similarity). Interacts with several RNA helicases, including DHX9, DDX21, and DDX39A/DDX39, and with DNA topoisomerase TOP2A (By similarity). Directly interacts with AICDA/AID (PubMed:20507984). Interacts with the glucocorticoid receptor NR3C1 (By similarity). Interacts with MCM3 (PubMed:10733502).|||Cytoplasm|||Embryonic lethal at 11.5 dpc.|||Expressed at low levels in lymphoid organs, including thymus, spleen and lymph nodes (PubMed:10733502). Up-regulated in stimulated B-cells in spleen and Peyer's patch germinal centers (at protein level) (PubMed:11526238).|||Nucleus|||Nucleus envelope|||Phosphorylation at Ser-502 is induced in B-cells by CD40-stimulation, but not by bacterial lipopolysaccharide (LPS).|||Up-regulated in B-cells by CD40 stimulation and bacterial lipopolysaccharide (LPS) (at protein level).|||nuclear pore complex|||nucleoplasm http://togogenome.org/gene/10090:Hand2 ^@ http://purl.uniprot.org/uniprot/Q61039 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND1 and HEY1, HEY2 and HEYL (hairy-related transcription factors).|||Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries. Required for vascular development and regulation of angiogenesis, possibly through a VEGF signaling pathway. Also plays an important role in limb development, particularly in the establishment of anterior-posterior polarization, acting as an upstream regulator of sonic hedgehog (SHH) induction in the limb bud. Is involved in the development of branchial arches, which give rise to unique structures in the head and neck. Binds DNA on E-box consensus sequence 5'-CANNTG-3'.|||Heart and aorta.|||High extraembryonic expression is detected at 7.5 dpc in the maternally derived deciduum. Also detected along the yolk sac vessels during the process of remodeling at 9.5-10.0 dpc. Within the embryo, detected at 7.5 dpc in the lateral mesoderm including the precardiac mesoderm. On day 8.5 pc expressed throughout the straight heart tube. In the caudal region of the embryo, expressed in the lateral mesoderm at the level of separation of the somatic and splanchnic mesoderm. On day 9.5 pc expressed throughout the developing cardiovascular region, most abundant in the outflow tract and in the first and second aortic arch arteries, and in pharyngeal arches. As the heart loops, the expression becomes restricted to the conotruncus and future right ventricle (endocardium and myocardium). At 10.5 dpc, highly expressed in the branchial arches, as well as in the truncus arteriosus, aortic sac, and the vascular mesenchyme between the third and fourth aortic arch arteries, which later gives rise to vascular smooth muscle cells and to the mesenchyme of the pharyngeal arch. At 13.5 dpc, barely detectable in the heart, but apparent in the neural crest-derived sympathetic trunk and adrenal medulla, a pattern similar to that of HAND1. In the developing limbs, expression is detected in the posterior mesoderm of the buds at 9.5 dpc. It is then progressively down-regulated at the anterior of the limb buds so that a gradient expression along the anterior-posterior axis of the bud is established with higher expression at the posterior border. At later stages of limb development, expression is restricted to the posterior border of the zeugopod and to the posterior autopod. In the autopod, dynamic expression of HAND2 affects the interdigital regions, the lateral borders of the digits and eventually the developing ventral tendons. After 16 dpc, expression decreases throughout the embryo.|||Nucleus http://togogenome.org/gene/10090:Or8k17 ^@ http://purl.uniprot.org/uniprot/Q8VGS2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Birc7 ^@ http://purl.uniprot.org/uniprot/A2AWP0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions. Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and MAP3K7/TAK1. In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9.|||Autoubiquitinated and undergoes proteasome-mediated degradation.|||Belongs to the IAP family.|||Binds to caspase-9. Interaction with DIABLO/SMAC via the BIR domain disrupts binding to caspase-9 and apoptotic suppressor activity. Interacts with TAB1. In vitro, interacts with caspase-3 and caspase-7 via its BIR domain.|||Cytoplasm|||Golgi apparatus|||Nucleus|||The RING domain is essential for autoubiquitination.|||The truncated protein (tLivin) not only loses its anti-apoptotic effect but also acquires a pro-apoptotic effect. http://togogenome.org/gene/10090:Entrep1 ^@ http://purl.uniprot.org/uniprot/Q4FZH1 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ENTREP family.|||Cell membrane|||Early endosome membrane|||Functions as an activator of the E3 ubiquitin protein ligase ITCH in the ubiquitination of the CXCL12-activated CXCR4 receptor. Thereby, triggers CXCR4 endocytosis and desensitization, negatively regulating the CXCL12/CXCR4 signaling pathway.|||Gene prediction based on EST data.|||Gene prediction based on similarity to the human ortholog.|||Interacts with ITCH; enhances the ubiquitination of CXCR4 by ITCH and the subsequent endocytosis and desensitization of the receptor. Interacts with EPN1.|||Late endosome membrane|||Recycling endosome membrane|||The cytoplasmic PPxY motifs mediate interaction with the WW domains of ITCH. http://togogenome.org/gene/10090:Ankrd13a ^@ http://purl.uniprot.org/uniprot/Q80UP5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts (via the UIM 3 and 4 repeats) with EGFR (ubiquitinated); the interaction is direct, inhibited by ANKRD13A monoubiquitination and may regulate EGFR internalization.|||Late endosome|||Monoubiquitinated, inhibits interaction with ubiquitinated EGFR.|||The UIM repeats 3 and 4 are required for binding to ubiquitinated EGFR and 'Lys-63'-linked ubiquitin.|||Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane (By similarity). http://togogenome.org/gene/10090:Gypc ^@ http://purl.uniprot.org/uniprot/Q78HU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycophorin-C family.|||Cell membrane http://togogenome.org/gene/10090:Hyal2 ^@ http://purl.uniprot.org/uniprot/O35632|||http://purl.uniprot.org/uniprot/Q3UZE4 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 56 family.|||Cell membrane|||Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product which is further hydrolyzed by sperm hyaluronidase to give small oligosaccharides. Displays very low levels of activity. Associates with and negatively regulates MST1R (By similarity).|||Interacts with MST1R.|||Was originally thought to be lysosomal.|||Widely expressed. In the brain, expressed during embryonic stages but expression decreases after birth and is barely detectable in adult brain. http://togogenome.org/gene/10090:Dhx58 ^@ http://purl.uniprot.org/uniprot/Q99J87 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a regulator of RIGI and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to RIGI and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on RIG-I signaling may involve the following mechanisms: competition with RIGI for binding to the viral RNA, binding to RIGI and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by RIGI and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate.|||Belongs to the helicase family. RLR subfamily.|||By interferon (IFN), virus infection, or intracellular dsRNA.|||Cytoplasm|||Embryonic lethality at a high frequency. Adult female that survive show an enlarged uterus filled with fluid resulting from vaginal atresia.|||Highly expressed in mammary tissues. Expressed in liver and testis. Expressed at lower level in spleen, embryo, mammary gland and breast tumors.|||Monomer in the absence of dsRNA. Homodimer in the presence of dsRNA. Interacts with RIGI (via CARD domain), MAVS/IPS1 and DDX60. Found in a complex with RIGI and IFIH1/MDA5. Interacts with ANKRD17. Directly interacts with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates (By similarity).|||The RLR CTR domain is capable of inhibiting dimerization and signaling of RIGI and also facilitates binding of dsRNA. http://togogenome.org/gene/10090:Golga7b ^@ http://purl.uniprot.org/uniprot/Q9D428 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ERF4 family.|||Cell membrane|||Golgi apparatus membrane|||Palmitoylated by ZDHHC5. Palmitoylation is required for the maintenance of ZDHHC5 at the plasma membrane.|||Play a role in cell adhesion by regulating the plasma membrane localization of the palmitoyltransferase ZDHHC5. May be involved in protein transport from Golgi to cell surface. http://togogenome.org/gene/10090:Akr1c13 ^@ http://purl.uniprot.org/uniprot/Q571M4|||http://purl.uniprot.org/uniprot/Q8VC28 ^@ Function|||Similarity ^@ Belongs to the aldo/keto reductase family.|||Catalyzes the dehydrogenation of 17-beta-hydroxysteroids. May also exhibit significant activity with a variety of cyclic and alicyclic alcohols. Uses both NAD and NADP, but the activity is much greater with NAD than with NADP (By similarity). http://togogenome.org/gene/10090:Apobec1 ^@ http://purl.uniprot.org/uniprot/P51908|||http://purl.uniprot.org/uniprot/Q3U9G8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytidine and deoxycytidylate deaminase family.|||Binds 1 Zn(2+) ion per subunit.|||Cytidine deaminase catalyzing the cytidine to uridine postranscriptional editing of a variety of mRNAs. Form complexes with cofactors that confer differential editing activity and selectivity. Responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the apolipoprotein B mRNA. Also involved in CGA (Arg) to UGA (Stop) editing in the NF1 mRNA (By similarity). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894).|||Cytoplasm|||Expressed in the spleen. Expressed at lower level in the kidney, testis, lung, brain and liver.|||Homodimer. Interacts with A1CF; form an mRNA editing complex. Interacts with RBM47; form an mRNA editing complex. Found in a complex with CELF2/CUGBP2 and A1CF. Interacts with HNRPAB. Interacts with SYNCRIP.|||Nucleus http://togogenome.org/gene/10090:Cfap74 ^@ http://purl.uniprot.org/uniprot/Q3UY96 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ As part of the central apparatus of the cilium axoneme may play a role in cilium movement. May play an important role in sperm architecture and function.|||Belongs to the CFAP74 family.|||Probable cloning artifact.|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Scyl2 ^@ http://purl.uniprot.org/uniprot/Q8CFE4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Component of the AP2-containing clathrin coat that may regulate clathrin-dependent trafficking at plasma membrane, TGN and endosomal system. A possible serine/threonine-protein kinase toward the beta2-subunit of the plasma membrane adapter complex AP2 and other proteins in presence of poly-L-lysine has not been confirmed (By similarity). By regulating the expression of excitatory receptors at synapses, plays an essential role in neuronal function and signaling and in brain development (PubMed:26203146).|||Could autophosphorylate in presence of poly-L-lysine.|||Disruption of the gene results in perinatal lethality due to impaired neuronal functions. Mutant animals that survive to adulthood show growth retardation and severe sensorimotor deficits. The neurologic deficits in these mice is associated with the degeneration of several neuronal populations, most notably CA3 pyramidal neurons of the hippocampus, resulting from excitotoxicity. This is associated with excessive expression and activation of calcium-permeable glutamate receptors at the synapse. A wide variety of clathrin-mediated functions and lysosomal pathways are however preserved in mutant mice.|||Endosome membrane|||Interacts with clathrin and AP2B1; the interaction mediates the association with the AP-2 complex.|||Ubiquitously expressed.|||clathrin-coated vesicle|||trans-Golgi network membrane http://togogenome.org/gene/10090:Pdlim1 ^@ http://purl.uniprot.org/uniprot/O70400 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoskeletal protein that may act as an adapter that brings other proteins (like kinases) to the cytoskeleton (By similarity). Involved in assembly, disassembly and directioning of stress fibers in fibroblasts. Required for the localization of ACTN1 and PALLD to stress fibers. Required for cell migration and in maintaining cell polarity of fibroblasts (By similarity).|||Detected throughout the developing heart.|||Expressed in heart, lung, spleen, testis and skeletal muscle.|||Interacts with ACTN1, ACTN2 and ACTN4 (By similarity). Interacts with PDLIM4 (By similarity).|||Z line|||cytoskeleton http://togogenome.org/gene/10090:Macf1 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQA6|||http://purl.uniprot.org/uniprot/B1ARU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the plakin or cytolinker family.|||cytoskeleton http://togogenome.org/gene/10090:Crppa ^@ http://purl.uniprot.org/uniprot/A0A1Y7VK76|||http://purl.uniprot.org/uniprot/A0A1Y7VM96|||http://purl.uniprot.org/uniprot/Q5RJG7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IspD/TarI cytidylyltransferase family. IspD subfamily.|||Cytidylyltransferase required for protein O-linked mannosylation (By similarity). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate (By similarity). CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (By similarity). Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively (By similarity). Not involved in dolichol production (By similarity).|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Bcl3 ^@ http://purl.uniprot.org/uniprot/Q9Z2F6 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation.|||Component of a complex consisting of the NF-kappa-B p52-p52 homodimer and BCL3. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Interacts with N4BP2, COPS5 and PIR (By similarity). Interacts with CYLD.|||Contributes to the regulation of transcriptional activation of NF-kappa-B target genes. In the cytoplasm, inhibits the nuclear translocation of the NF-kappa-B p50 subunit (By similarity). In the nucleus, acts as transcriptional activator that promotes transcription of NF-kappa-B target genes. Contributes to the regulation of cell proliferation.|||Cytoplasm|||It is uncertain whether Met-1 or Met-9 is the initiator.|||Nucleus|||Polyubiquitinated. Ubiquitination via 'Lys-63'-linked ubiquitin chains is required for nuclear accumulation. Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin chains. Deubiquitination by CYLD prevents nuclear accumulation.|||perinuclear region http://togogenome.org/gene/10090:Vmn2r108 ^@ http://purl.uniprot.org/uniprot/E9PYS0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Szrd1 ^@ http://purl.uniprot.org/uniprot/Q6NXN1 ^@ Similarity ^@ Belongs to the SZRD1 family. http://togogenome.org/gene/10090:Katnip ^@ http://purl.uniprot.org/uniprot/Q8C753 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with microtubules. Interacts with 4 subunits of the katanin complex: KATNA1, KATNAL1, KATNB1 and KATNBL1.|||Knockout mice frequently display brain-specific defects, resulting in a noncommunicating (obstructive) hydrocephalus.|||May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex.|||cilium axoneme|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Uqcrc2 ^@ http://purl.uniprot.org/uniprot/Q9DB77 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-159 and Lys-250 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the peptidase M16 family. UQCRC2/QCR2 subfamily.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783, PubMed:30666338). Interacts with RAB5IF (PubMed:31536960). Interacts with STMP1 (PubMed:35101990).|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties. May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (By similarity).|||Expressed in neurons and astrocytes of the cerebral cortex and hippocampus (at protein level).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ess2 ^@ http://purl.uniprot.org/uniprot/O70279|||http://purl.uniprot.org/uniprot/Q3UFM6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ESS2 family.|||Highly expressed during embryogenesis from 7 dpc onwards.|||Identified in the spliceosome C complex. Interacts with FRA10AC1.|||In the adult, widely expressed with highest expression in the testis and brain. Also widely expressed in the embryo with highest levels in the anterior pons.|||May be involved in pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Dera ^@ http://purl.uniprot.org/uniprot/Q91YP3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DeoC/FbaB aldolase family. DeoC type 2 subfamily.|||Catalyzes a reversible aldol reaction between acetaldehyde and D-glyceraldehyde 3-phosphate to generate 2-deoxy-D-ribose 5-phosphate. Participates in stress granule (SG) assembly. May allow ATP production from extracellular deoxyinosine in conditions of energy deprivation.|||Cytoplasm|||Cytoplasmic granule|||Interacts with YBX1.|||Nucleus http://togogenome.org/gene/10090:Mrps27 ^@ http://purl.uniprot.org/uniprot/Q8BK72 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS27 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins (By similarity). Interacts with NOA1 (By similarity). Interacts with MIEF1 upstream open reading frame protein (By similarity). Interacts with METTL17 (PubMed:31487196).|||Cytoplasm|||Mitochondrion|||RNA-binding component of the mitochondrial small ribosomal subunit (mt-SSU) that plays a role in mitochondrial protein synthesis. Stimulates mitochondrial mRNA translation of subunit components of the mitochondrial electron transport chain. Binds to the mitochondrial 12S rRNA (12S mt-rRNA) and tRNA(Glu). Overexpressed in hepatocellular carcinoma tissues compared with adjacent non-tumoral liver tissues. http://togogenome.org/gene/10090:Glipr1 ^@ http://purl.uniprot.org/uniprot/Q4QQK5|||http://purl.uniprot.org/uniprot/Q9CWG1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CRISP family.|||Membrane http://togogenome.org/gene/10090:Hdac3 ^@ http://purl.uniprot.org/uniprot/O88895|||http://purl.uniprot.org/uniprot/Q9JM08 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone deacetylase family. HD Type 1 subfamily.|||Belongs to the histone deacetylase family. HD type 1 subfamily.|||Cytoplasm|||Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation.|||Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:23911289, PubMed:30279482). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:23911289). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:19204783). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (By similarity). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (PubMed:26776516). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (PubMed:26776516). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (PubMed:19037247). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (By similarity). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (By similarity). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (By similarity). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:30279482). Catalyzes decrotonylation of MAPRE1/EB1 (By similarity).|||Interacts with HDAC7 and HDAC9 (PubMed:10984530, PubMed:11022042, PubMed:15711539). Interacts with DAXX, KDM4A, HDAC10 and DACH1 (PubMed:12130660). Found in a complex with NCOR1 and NCOR2 (By similarity). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (By similarity). Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY (PubMed:16537907). Interacts with BTBD14B (By similarity). Interacts with GLIS2 (PubMed:16326862). Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:19204783). Component of the Notch corepressor complex (By similarity). Interacts with CBFA2T3 and NKAP (PubMed:11533236). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (By similarity). Interacts with ZMYND15 (PubMed:20675388). Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements (By similarity). Interacts with INSM1 (By similarity). Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow (By similarity). Interacts (via C-terminus) with CCAR2 (via N-terminus) (By similarity). Interacts with and deacetylates MEF2D (By similarity). Interacts with BEND3 (By similarity). Interacts with NKAPL (PubMed:25875095). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (By similarity). Interacts weakly with CRY1; this interaction is enhanced in the presence of FBXL3 (PubMed:26776516). Interacts with FBXL3 and BMAL1 (PubMed:26776516). Interacts with NCOR1 (PubMed:19037247). Interacts with RARA (By similarity). Interacts with SETD5 (PubMed:30455454).|||Liver-specific knockout mice exhibit low amplitude of circadian rhythms, dampened E-box-driven transcription and a significant reduction in the protein levels of BMAL1 and CRY1 in the liver.|||Nucleus|||Sumoylated in vitro.|||cytosol http://togogenome.org/gene/10090:Tbc1d22a ^@ http://purl.uniprot.org/uniprot/Q8R5A6 ^@ Function|||Subunit ^@ Homodimer. Interacts with ACBD3 and ARFGEF1. Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ.|||May act as a GTPase-activating protein for Rab family protein(s). http://togogenome.org/gene/10090:Zar1l ^@ http://purl.uniprot.org/uniprot/C3VD30 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates during oocyte growth and degradaded after meiotic resumption: present in germinal vesicle (GV) stage oocytes and decreases during meiotic maturation and fertilization, and undetectable in 2-cell embryos.|||Belongs to the ZAR1 family.|||Cytoplasmic ribonucleoprotein granule|||Disordered region at the N-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of membraneless compartments that store maternal mRNAs in oocytes.|||Expressed in oocytes and zygotes (PubMed:20014101, PubMed:31598710). Predominantly expressed in maturing oocytes before maternal-to-zygotic transition (MZT) (PubMed:31598710). Less abundant than Zar1 (PubMed:31598710).|||Interacts with YBX2.|||No visible phenotype: mice are viable and females are fertile (PubMed:31598710). Mice lacking Zar1 and Zar1l oocytes display delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy (PubMed:31598710). The grown oocytes of Zar1 and Zar1l mutant mice contain decreased levels of many maternal mRNAs and display a reduced level of protein synthesis (PubMed:31598710).|||The 3CxxC-type mediates binding to the 3'-UTR of mRNAs.|||mRNA-binding protein required for maternal mRNA storage, translation and degradation during oocyte maturation (PubMed:31598710). Probably promotes formation of some phase-separated membraneless compartment that stores maternal mRNAs in oocytes: acts by undergoing liquid-liquid phase separation upon binding to maternal mRNAs (By similarity). Binds to the 3'-UTR of maternal mRNAs, inhibiting their translation (PubMed:31598710). http://togogenome.org/gene/10090:Dnase1l2 ^@ http://purl.uniprot.org/uniprot/Q9D1G0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DNase I family.|||Cytoplasm|||Divalent cation-dependent acid DNA endonuclease involved in the breakdown of the nucleus during corneocyte formation of epidermal keratinocytes. May play an immune role by eliminating harmful DNA released into the extracellular environment by damaged epidermal cells (By similarity).|||Secreted http://togogenome.org/gene/10090:Atp6ap2 ^@ http://purl.uniprot.org/uniprot/Q1XID4|||http://purl.uniprot.org/uniprot/Q9CYN9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Conditional knockout mice lacking Atp6ap2 in glutamatergic neurons display increased spontaneous locomotor activity and altered fear memory; show abnormal number and morphology of synapses, presynaptic transmission and autophagy defects that lead to axonal and neuronal degeneration in the cortex and hippocampus (PubMed:26376863). Conditional knockout mice lacking Atp6ap2 in the liver display liver damage, hypoglycosylation of serum proteins and autophagy defects (PubMed:29127204, PubMed:26376863). Conditional knockout mice lacking Atp6ap2 in cortical neurons die around 4 weeks of age (PubMed:30985297). It is associated with a flattened forehead and deficits in neural cell generation and/or survival compared to controls. Mutant embryonic cortex shows reduced proliferation of progenitor neural cells with premature exit of the cell cycle, premature differentiation, and apoptosis. There is also evidence of lysosomal dysfunction, impaired protein degradation in autophagolysosomes, and dysregulation of the mTOR kinase pathway.|||Endoplasmic reticulum membrane|||Endosome membrane|||Expressed at 12 dpc throughout the developing cortex with notable apical enrichment in radial glial cells (RGCs) along the ventricular surface.|||Expressed in glutamatergic and GABAergic neurons with highest levels in the cortex, the hippocampus, the medial habenular nucleus, the cerebellum, the medulla and the olfactory bulb (at protein level).|||Interacts with renin. Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump. Interacts (via N-terminus) with ATP6AP1 (via N-terminus). Interacts with ATP6V0D1; ATP6V0D1 is a V-ATPase complex subunit and the interaction promotes V-ATPase complex assembly. Interacts with TMEM9; TMEM9 is a V-ATPase assembly regulator and the interaction induces the interaction with ATP6V0D1. Interacts with VMA21 (via N-terminus); VMA21 is a V-ATPase accessory component.|||Lysosome membrane|||Membrane|||Multifunctional protein which functions as a renin, prorenin cellular receptor and is involved in the assembly of the lysosomal proton-transporting V-type ATPase (V-ATPase) and the acidification of the endo-lysosomal system (By similarity). May mediate renin-dependent cellular responses by activating ERK1 and ERK2 (By similarity). By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, may also play a role in the renin-angiotensin system (RAS) (By similarity). Through its function in V-type ATPase (v-ATPase) assembly and acidification of the lysosome it regulates protein degradation and may control different signaling pathways important for proper brain development, synapse morphology and synaptic transmission (PubMed:26376863, PubMed:29127204, PubMed:30985297).|||Phosphorylated.|||Proteolytically cleaved by a furin-like convertase in the trans-Golgi network to generate N- and C-terminal fragments.|||autophagosome membrane|||axon|||clathrin-coated vesicle membrane|||dendritic spine membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:F11r ^@ http://purl.uniprot.org/uniprot/O88792 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the immunoglobulin superfamily.|||Cell membrane|||Interacts with the ninth PDZ domain of MPDZ (By similarity). Interacts with the first PDZ domain of PARD3 (PubMed:11447115). The association between PARD3 and PARD6B probably disrupts this interaction (PubMed:11447115). Interacts with ITGAL (via I-domain) (By similarity).|||Seems to play a role in epithelial tight junction formation. Appears early in primordial forms of cell junctions and recruits PARD3 (PubMed:11447115). The association of the PARD6-PARD3 complex may prevent the interaction of PARD3 with JAM1, thereby preventing tight junction assembly (PubMed:11447115). Plays a role in regulating monocyte transmigration involved in integrity of epithelial barrier (PubMed:9660867). Ligand for integrin alpha-L/beta-2 involved in memory T-cell and neutrophil transmigration (By similarity). Involved in platelet activation (By similarity).|||The Ig-like V-type 2 domain is necessary and sufficient for interaction with integrin alpha-L/beta-2.|||tight junction http://togogenome.org/gene/10090:Sass6 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFC9|||http://purl.uniprot.org/uniprot/Q80UK7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Central scaffolding component of the centrioles ensuring their 9-fold symmetry. Required for centrosome biogenesis and duplication: required both for mother-centriole-dependent centriole duplication and deuterosome-dependent centriole amplification in multiciliated cells (PubMed:24240477). Required for the recruitment of STIL to the procentriole and for STIL-mediated centriole amplification (By similarity).|||Nine homodimers form a cartwheel structure with an internal diameter of 23 nM and radial spokes connecting to the microtubule triplets. Interacts with FBXW5. Forms a complex with CENPJ and STIL. Interacts with NUP62 and TUBG1 at the centrosome. Interacts with CENATAC; the interaction increases with CENATAC acetylation. Interacts with FZR1; the interaction is regulated by CENATAC and leads to SASS6 proteasomal degradation (By similarity).|||The 35 nM long coiled-coil domain mediates homodimerization while the globular N-terminus links the dimers at an angle of 40 degrees to form the inner ring.|||Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during S phase, leading to its degradation and preventing centriole reduplication. Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex, leading to its degradation and preventing centriole reduplication.|||centriole|||centrosome http://togogenome.org/gene/10090:Rnf187 ^@ http://purl.uniprot.org/uniprot/Q8BFX1 ^@ Caution|||Domain|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Arginine methylation by PRMT1 stabilizes RNF187 by facilitating K63-linked ubiquitin chain formation, and enables dimerization, c-Jun interaction and subsequent AP1 target gene expression.|||Cytoplasm|||E3 ubiquitin-protein ligase that acts as a coactivator of JUN-mediated gene activation in response to growth factor signaling via the MAP3K1 pathway, independently from MAPK8.|||Homodimer (By similarity). Interacts with JUN, independently of JUN phosphorylation (PubMed:20852630). Interacts (via C-terminus) with TRIM7 (By similarity).|||Nucleus|||The RING-type zinc finger domain is required for E3 ligase activity.|||This sequence initiates at a CTG codon.|||Ubiquitinated; undergoes 'Lys-48'-linked autoubiquitination in the absence of growth factors and MAP3K1-induced 'Lys-63'-linked polyubiquitination. 'Lys-48'-autoubiquitination leads to degradation by the proteasome, while MAP3K1-induced 'Lys-63'-linked polyubiquitination results in the stabilization of the protein. 'Lys-48'- and 'Lys-63'-linked polyubiquitinations occur most probably on the same 3 C-terminal lysine residues (Lys-195, Lys-224 and Lys-225) and are thus mutually exclusive. Other sites of ubiquitination are not excluded. 'Lys-63'-linked polyubiquitination by TRIM7 in response to growth factor signaling via the MEK/ERK pathway enhances protein stability.|||Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon. http://togogenome.org/gene/10090:Pole ^@ http://purl.uniprot.org/uniprot/Q3UR94|||http://purl.uniprot.org/uniprot/Q80XH7|||http://purl.uniprot.org/uniprot/Q9WVF7 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-B family.|||Binds 1 [4Fe-4S] cluster.|||Catalytic component of the DNA polymerase epsilon complex (By similarity). Participates in chromosomal DNA replication. Required during synthesis of the leading DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). It is also involved in DNA synthesis during DNA repair (By similarity).|||Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1.|||DNA polymerase II participates in chromosomal DNA replication.|||Nucleus|||The CysA-type zinc finger is required for PCNA-binding.|||The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.|||The DNA polymerase activity domain resides in the N-terminal half of the protein, while the C-terminus is necessary for maintenance of the complex. http://togogenome.org/gene/10090:Rgl3 ^@ http://purl.uniprot.org/uniprot/Q3UYI5 ^@ Domain|||Function|||Subunit|||Tissue Specificity ^@ Guanine nucleotide exchange factor (GEF) for Ral-A. Potential effector of GTPase HRas and Ras-related protein M-Ras. Negatively regulates Elk-1-dependent gene induction downstream of HRas and MEKK1.|||Interacts with GTP-bound forms of RIT1, HRAS and MRAS.|||The Ras-associating domain plays a central role in the activation of Ral-A GDP/GTP exchange activity.|||Widely expressed. Expressed at high levels in the liver and kidney. http://togogenome.org/gene/10090:Nudt3 ^@ http://purl.uniprot.org/uniprot/B2KF67|||http://purl.uniprot.org/uniprot/Q9JI46 ^@ Cofactor|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. DIPP subfamily.|||Binds 3 Mg(2+) ions per subunit.|||Chimeric at the C-terminus.|||Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction (PubMed:15212765). InsP6 (inositol hexakisphosphate) is not a substrate (By similarity). Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate (Ap5A) being the preferred substrates (By similarity). The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A (By similarity). Also able to hydrolyze 5- phosphoribose 1-diphosphate (By similarity). Acts as a negative regulator of the ERK1/2 pathway (PubMed:15212765). Acts as a decapping enzyme that can hydrolyze both monomethylated and unmethylated capped RNAs (PubMed:23353937). Hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates generating m7GMP + ppRNA and m7GDP + pRNA (PubMed:23353937). Modulates the stability of a subset of mRNAs implicated in cell motility (By similarity). Divalent cations zinc, magnesium and manganese determine its substrate specificity (By similarity). Exhibits diphosphoinositol polyphosphate phosphohydrolase in the presence of magnesium ions, diadenosine hexaphosphate hydrolase activity in the presence of manganese ions and endopolyphosphatase activity in the presence of zinc ions (By similarity). Plays an important role in limiting DNA damage and maintaining cell survival upon oxidative stress via its endopolyphosphatase activity (By similarity).|||Cytoplasm|||Monomer.|||Nucleus|||Present in heart, lung, liver and spleen (at protein level). Widely expressed. http://togogenome.org/gene/10090:Wnt8a ^@ http://purl.uniprot.org/uniprot/Q0VBT1|||http://purl.uniprot.org/uniprot/Q64527 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Wnt family.|||By retinoic acid.|||Expression in early stages of embryogenesis. Expression begins in the posterior region of early primitive streak-stage embryos and after it spreads into the embryonic ectoderm up to a sharp rostral boundary at the base of the developing headfolds. Expressed transiently in the newly formed mesoderm. Expression is down-regulated during somitogenesis. The expression is highly restricted during gastrulation and neurulation, both temporally and spatially.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Ligand for members of the frizzled family of seven transmembrane receptors. Plays a role in embryonic patterning.|||Palmitoleoylation is required for efficient binding to frizzled receptors (By similarity). Depalmitoleoylation leads to Wnt signaling pathway inhibition (By similarity).|||Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT8A.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Dnajc5 ^@ http://purl.uniprot.org/uniprot/P60904 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a co-chaperone for the SNARE protein SNAP-25 (PubMed:22187053). Involved in the calcium-mediated control of a late stage of exocytosis (PubMed:20847230). Acts as a general chaperone in regulated exocytosis (By similarity). May have an important role in presynaptic function (By similarity). May be involved in calcium-dependent neurotransmitter release at nerve endings (By similarity).|||Cell membrane|||Defective SNAP-25 function, which causes neurodegeneration by impairing SNARE-complex assembly (PubMed:22187053).|||Formation of the chaperone complex DNAJC5/HSC70 is not regulated by phosphorylation (PubMed:20847230). Ser-10 phosphorylation induces an order-to-disorder transition triggering the interaction with Lys-58 (By similarity). This conformational switch modulates DNAJC5's cellular functions by reducing binding to syntaxin and synaptogamin without altering HSC70 interactions (By similarity).|||Homodimer (Probable). Interacts with the chaperone complex consisting of HSC70 and SGTA (PubMed:17034881, PubMed:20847230). Interacts with ZDHHC13 (via ANK repeats) (PubMed:25253725, PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:25253725, PubMed:26198635). Interacts with SYT1, SYT5 and SYT7, and with SYT9, forming a complex with SNAP25 (PubMed:20847230). The interaction with SYT9 is stimulated tenfold in presence of calcium (PubMed:20847230).|||Melanosome|||Membrane|||Palmitoylated (PubMed:17034881). Could be palmitoylated by DHHC3, DHHC7, DHHC15 and DHHC17 (By similarity). Palmitoylation occurs probably in the cysteine-rich domain and regulates DNAJC5 membrane attachment (PubMed:17034881).|||chromaffin granule membrane|||cytosol http://togogenome.org/gene/10090:Cebpb ^@ http://purl.uniprot.org/uniprot/P28033|||http://purl.uniprot.org/uniprot/Q3UPN9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in myoblasts. Enriched in brown adipose tissue (BAT) versus white adipose tissue (WAT). Expressed in hepatocytes (at protein level). Expressed in T lymphocytes (PubMed:16585579). The expression in granulosa cells of antral follicles is induced by luteinizing hormone (PubMed:9303532). Expressed in chondrocytes and osteoblasts (at protein level) (PubMed:19440205).|||Acetylated. Acetylation at Lys-39 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function. Deacetylation by HDAC1 represses its transactivation activity (PubMed:18486321). Acetylated by KAT2A and KAT2B within a cluster of lysine residues between amino acids 98-102, this acetylation is strongly induced by glucocorticoid treatment and enhances transactivation activity (PubMed:17301242).|||Acts as a dominant negative through heterodimerization with isoform 2 (By similarity). Promotes osteoblast differentiation and osteoclastogenesis (PubMed:19440205).|||At 9.5 dpc, expressed in the chorionic plate and ectoplacental cone. From 10.5 dpc to at least 11.5 dpc, is also expressed in the trophoblast cells of the three placenta layers (PubMed:15509779). Expressed in monocytic precursors but is vanished during differentiation into osteoclasts. The expression increases during osteoblast differentiation (PubMed:19440205).|||Belongs to the bZIP family. C/EBP subfamily.|||Binds DNA as a homodimer and as a heterodimer. Interacts with ATF4. Binds DNA as a heterodimer with ATF4 (PubMed:11018027). Interacts with MYB; within the complex, MYB and CEBPB bind to different promoter regions (PubMed:11792321). Can form stable heterodimers with CEBPA, CEBPD and CEBPE (By similarity). Interacts with SIX1 (PubMed:27923061). Isoform 2 and isoform 3 also form heterodimers (By similarity). Interacts with TRIM28 and PTGES2 (PubMed:9742105, PubMed:15879117). Interacts with PRDM16 (PubMed:19641492). Interacts with CCDC85B (PubMed:15644333). Forms a complex with THOC5 (PubMed:19015024). Interacts with ZNF638; this interaction increases transcriptional activation (PubMed:21602272). Interacts with CIDEA and CIDEC (PubMed:22245780). Interaction with CIDEA increases transcriptional activation of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH. Interaction with CIDEC increases transcriptional activation of SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. Interacts with DDIT3/CHOP. Interacts with EP300; recruits EP300 to chromatin. Interacts with RORA; the interaction disrupts interaction with EP300 (PubMed:19324970). Interacts (not methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1 (PubMed:20111005). Interacts with KAT2A and KAT2B (PubMed:17301242). Interacts with ATF5; EP300 is required for ATF5 and CEBPB interaction and DNA binding (PubMed:24216764). Interacts with NFE2L1; the heterodimer represses expression of DSPP during odontoblast differentiation (By similarity).|||Cytoplasm|||Embryos display defects in brown fat tissue development (PubMed:19641492). Females are sterile, ovaries lack corpora lutea (PubMed:9303532). Upon bacterial infection, animals show impaired bactericidal activity and die within 3 days (PubMed:17911624). Posthepatectomy, animals show a reduced regenerative response with DNA synthesis decreased to 25% of normal in hepatocytes and a prolonged period of hypoglycemia (PubMed:9727068). Animals show osteopenia with decreased bone formation and enhanced ostecolastogenesis. Long bones have a 1.6 fold diminished bone volume with a reduction of the number and thickness of bone trabeculae (PubMed:19440205). Mutants of isoform 2 show impaired CSF3/G-CSF production by macrophages, IFNG production by CD4(+) T-cells and granuloma formation in liver. Upon bacterial infection, mutants of isoform 2 die within 6 days. Resistant to LPS-induced endotoxin shock (PubMed:17911624). Double knockout CEBPA and CEBPB results in embryonic developmental arrest and death at around 10 dpc to 11 dpc, associated with a gross placenta failure (PubMed:15509779).|||Essential for gene expression induction in activated macrophages. Plays a major role in immune responses such as CD4(+) T-cell response, granuloma formation and endotoxin shock. Not essential for intracellular bacteria killing.|||Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:16585579, PubMed:17911624, PubMed:18486321, PubMed:20111005). Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis (PubMed:9727068, PubMed:10635333, PubMed:17301242, PubMed:17601773, PubMed:19478079, PubMed:24061474, PubMed:24216764). The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications. During early embryogenesis, plays essential and redundant roles with CEBPA (PubMed:15509779). Has a promitotic effect on many cell types such as hepatocytes and adipocytes but has an antiproliferative effect on T-cells by repressing MYC expression, facilitating differentiation along the T-helper 2 lineage (PubMed:9727068, PubMed:10635333, PubMed:16585579). Binds to regulatory regions of several acute-phase and cytokines genes and plays a role in the regulation of acute-phase reaction and inflammation. Also plays a role in intracellular bacteria killing (PubMed:17911624). During adipogenesis, is rapidly expressed and, after activation by phosphorylation, induces CEBPA and PPARG, which turn on the series of adipocyte genes that give rise to the adipocyte phenotype. The delayed transactivation of the CEBPA and PPARG genes by CEBPB appears necessary to allow mitotic clonal expansion and thereby progression of terminal differentiation (PubMed:15985551, PubMed:17301242, PubMed:17601773, PubMed:20194620). Essential for female reproduction because of a critical role in ovarian follicle development (PubMed:9303532). Restricts osteoclastogenesis (PubMed:19440205). Together with NFE2L1; represses expression of DSPP during odontoblast differentiation (By similarity).|||Major isoform.|||Methylated. Methylation at Arg-3 by CARM1 and at Lys-39 by EHMT2, inhibits transactivation activity. Methylation is probably inhibited by phosphorylation at Thr-188.|||Nucleus|||O-glycosylated, glycosylation at Ser-180 and Ser-181 prevents phosphorylation on Thr-188, Ser-184 and Thr-179 and DNA binding activity which delays the adipocyte differentiation program.|||Phosphorylated at Thr-188 by MAPK and CDK2, serves to prime phosphorylation at Thr-179 and Ser-184 by GSK3B and acquire DNA-binding as well as transactivation activities, required to induce adipogenesis. MAPK and CDK2 act sequentially to maintain Thr-188 in the primed phosphorylated state during mitotical cloning expansion and thereby progression of terminal differentiation. Phosphorylation at Thr-217 enhances transactivation activity. Phosphorylation at Ser-276 in response to calcium increases transactivation activity (PubMed:1314426). Phosphorylated at Thr-188 by RPS6KA1 (By similarity).|||Sumoylated by polymeric chains of SUMO2 or SUMO3. Sumoylation at Lys-133 is required for inhibition of T-cells proliferation (PubMed:16585579). In adipocytes, sumoylation at Lys-133 by PIAS1 leads to ubiquitination and subsequent proteasomal degradation (PubMed:24061474). Desumoylated by SENP2, which abolishes ubiquitination and stabilizes protein levels (PubMed:20194620).|||Ubiquitinated, leading to proteasomal degradation.|||Up-regulated by cold exposure. http://togogenome.org/gene/10090:Slc35e4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0N3|||http://purl.uniprot.org/uniprot/Q8K3D6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPT transporter family. SLC35E subfamily.|||Membrane|||Putative transporter. http://togogenome.org/gene/10090:Or5p58 ^@ http://purl.uniprot.org/uniprot/Q8VG03 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Methig1 ^@ http://purl.uniprot.org/uniprot/Q76I26 ^@ Subcellular Location Annotation ^@ Mitochondrion inner membrane http://togogenome.org/gene/10090:Smco3 ^@ http://purl.uniprot.org/uniprot/Q8BQM7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Arhgef10 ^@ http://purl.uniprot.org/uniprot/Q8C033 ^@ Developmental Stage|||Function|||PTM|||Tissue Specificity ^@ Found in the neuroepithelium of the meninges at 8.5 dpc, and in the roof plate of the rhombencephalon at 9.5 dpc. In 12.5 dpc embryos, it is ubiquitously expressed, with a pronounced expression in the neuroepithelium of brain vesicles, the neural tube, the ganglia and the neural layer of the retina.|||May play a role in developmental myelination of peripheral nerves.|||Methylated at Gln-1314 by N6AMT1.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Nox1 ^@ http://purl.uniprot.org/uniprot/Q8CIZ9 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (c-type) induced in VSMC by angiotensin II and injury to the artery.|||Cell membrane|||Expressed in colon and vascular smooth muscle cells (VSMC).|||NOX1, NOXA1, NOXO1, RAC1 and CYBA forms a functional multimeric complex supporting ROS production. Interacts with NOXA1 and NOXO1.|||Product of f-type and c-type mRNA, which differ only in 5'-UTR.|||Pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism.|||The oxidase activity is potentiated by NOXA1 and NOXO1.|||invadopodium membrane http://togogenome.org/gene/10090:Zfp335 ^@ http://purl.uniprot.org/uniprot/A2A5K6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters (By similarity). Enhances ligand-dependent transcriptional activation by nuclear hormone receptors (By similarity). Plays an important role in neural progenitor cell proliferation and self-renewal through the regulation of specific genes involved brain development, including REST (PubMed:23178126). Also controls the expression of genes involved in somatic development and regulates, for instance, lymphoblast proliferation (By similarity).|||Expressed at low levels in cerebral cortex, hippocampus and cerebellum (at protein level).|||In brain, expression peaks at 13-15 dpc, during cortical neurogenesis. At 8.5 dpc, expressed in forebrain and midbrain. At 14.5 dpc, expressed in ventricular zone, subventricular zone and cortical plate.|||Interacts with NCOA6; may enhance ligand-dependent transcriptional activation by nuclear hormone receptors (By similarity). Interacts with CNOT6 (By similarity). Interacts with CNOT9; the interaction is direct (By similarity). Component of a nuclear receptor-mediated transcription complex composed of at least ZNF335, CCAR2 and EMSY; the complex stimulates the transcription of nuclear receptor target genes such as SOX9 and HOXA1 (By similarity). Within the complex interacts with EMSY and interacts (via C-terminus) with CCAR2 (By similarity). Interacts with members of histone H3'Lys4'(H3K4) methyltransferase complexes ASH2L, CXXC1, KMT2A/MLL1, RBBP5, SETD1A and WDR5 (PubMed:23178126). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (By similarity). Interacts with RBBP5 and WDR5 (PubMed:23178126). Interacts with ASHL2 (By similarity). Components of this complex may associate with components of the ZNF335-CCAR2-EMSY nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (By similarity). Within this complex also interacts with HCFC1 and MKI67 (By similarity).|||Loss leads to embryonic lethality as early as 7.5 dpc. Brain-specific conditional knockout produces a brain with an essentially absent cortex lacking all cortical neurons.|||Nucleus http://togogenome.org/gene/10090:Or2t45 ^@ http://purl.uniprot.org/uniprot/Q8VFG7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm1993 ^@ http://purl.uniprot.org/uniprot/A6X8I0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Arsj ^@ http://purl.uniprot.org/uniprot/Q32KI8|||http://purl.uniprot.org/uniprot/Q8BM89 ^@ Cofactor|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Secreted|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Bag2 ^@ http://purl.uniprot.org/uniprot/Q91YN9 ^@ Function|||Subunit ^@ Binds to the ATPase domain of HSP/HSC70 chaperones. May interact with NWD1. Interacts with HSPA1A (via NBD), HSPA1B (via NBD) and HSPA8. May interact with DNJC9; the interaction seems to be histone-dependent (By similarity).|||Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. http://togogenome.org/gene/10090:Lrrc45 ^@ http://purl.uniprot.org/uniprot/Q8CIM1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the proteinaceous fiber-like linker between two centrioles, required for centrosome cohesion.|||Homomer. Interacts with CROCC/rootletin and CEP250. Interacts with CEP44.|||Phosphorylated by NEK2 during misosis, phosphorylation reduces centrosomal localization which subsequently leads to centrosome separation.|||centrosome http://togogenome.org/gene/10090:Rmnd1 ^@ http://purl.uniprot.org/uniprot/Q8CI78 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RMD1/sif2 family.|||Homooligomer.|||Mitochondrion|||Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome. http://togogenome.org/gene/10090:Pola1 ^@ http://purl.uniprot.org/uniprot/P33609 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-B family.|||Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis (PubMed:8253737, PubMed:8026492). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses.|||Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:8253737, PubMed:8026492). Within the complex, POLA1 directly interacts with PRIM2 (PubMed:8253737). Interacts with PARP1; this interaction functions as part of the control of replication fork progression. Interacts with MCM10 and WDHD1; these interactions recruit the polymerase alpha complex to the pre-replicative complex bound to DNA. Interacts with RPA1; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp (By similarity).|||Conserved regions II, IV, III and I are thought to be involved in substrate recognition, binding or PP(i) hydrolysis.|||Expressed in those zones containing proliferating cells in the developing embryonic neocortex, as well as in the lateral and medial ganglionic eminences. After birth, expressed in cells that remain proliferating in the ventricular and subventricular zone of the striatum.|||In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Gm4297 ^@ http://purl.uniprot.org/uniprot/D3YWB7 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Mup16 ^@ http://purl.uniprot.org/uniprot/A2CGB6|||http://purl.uniprot.org/uniprot/A9C496|||http://purl.uniprot.org/uniprot/P02762 ^@ Allergen|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in the urine of adult male mice but absent from that of females.|||Belongs to the calycin superfamily. Lipocalin family.|||Binds pheromones that are released from drying urine of males. These pheromones affect the sexual behavior of females.|||Causes an allergic reaction in human.|||Secreted|||There are about 15 group 1 MUP genes and their transcripts make up about 5% of male mouse liver RNA. http://togogenome.org/gene/10090:Rhobtb2 ^@ http://purl.uniprot.org/uniprot/Q91V93 ^@ Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Expressed in most tissues, with highest expression in brain.|||Interacts with HSP90AA1 and HSP90AB1. Interacts with CUL3. http://togogenome.org/gene/10090:Mat1a ^@ http://purl.uniprot.org/uniprot/Q91X83 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit ^@ An intrachain disulfide bond can be formed. The protein structure shows that the relevant Cys residues are in a position that would permit formation of a disulfide bond.|||Belongs to the AdoMet synthase family.|||Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.|||Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.|||Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate.|||Homotetramer (MAT-I); dimer of dimers. Homodimer (MAT-III).|||S-nitrosylation of Cys-121 inactivates the enzyme. http://togogenome.org/gene/10090:Atp2a1 ^@ http://purl.uniprot.org/uniprot/Q8R429 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.|||Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation.|||Endoplasmic reticulum membrane|||Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (PubMed:21697544, PubMed:22961106, PubMed:25640239). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium. This inhibition is regulated by the phosphorylation of PLN (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (PubMed:26816378).|||Interacts with sarcolipin (SLN) (PubMed:21697544, PubMed:22961106). Interacts with phospholamban (PLN) (PubMed:26816378). Interacts with myoregulin (MRLN) (PubMed:25640239). Interacts with DWORF (PubMed:26816378). Interacts with VMP1 (By similarity).|||Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum (PubMed:21697544, PubMed:22961106, PubMed:25640239, PubMed:26816378). Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:21697544, PubMed:22961106, PubMed:25640239, PubMed:26816378).|||PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices.|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Tcaf2 ^@ http://purl.uniprot.org/uniprot/Q921K8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCAF family.|||Cell membrane|||Interacts with TRPM8 (via N-terminus and C-terminus domains); the interaction inhibits TRPM8 channel activity. Interacts with TRPV6.|||Negatively regulates the plasma membrane cation channel TRPM8 activity. Involved in the recruitment of TRPM8 to the cell surface. Promotes prostate cancer cell migration stimulation in a TRPM8-dependent manner. http://togogenome.org/gene/10090:Ttll9 ^@ http://purl.uniprot.org/uniprot/A2APC3 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tubulin--tyrosine ligase family.|||Gln-155 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in brain and testis (PubMed:17499049). Expressed in heart, kidney and lung (PubMed:17499049). In the brain, expressed in ependymal cilia, cortex, corpus callosum and striatum (PubMed:23897886). In the testis, specifically expressed in the seminiferous tubules (PubMed:27257088).|||Males are infertile due to a reduction in sperm count and defective sperm motility. Sperm axonemes have shortened microtubule doublet 7 and reduced tubulin polyglutamylation, in particular of doublet 5. Reduced sperm motility is caused by frequent stalls of flagella due to defective switching in the bending direction.|||Probable tubulin polyglutamylase that generates side chains of glutamate on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of target proteins (PubMed:27257088). Similar to TTLL1, may acquire enzymatic activity only in complex with other proteins as it is most likely lacking domains important for autonomous activity (Probable). Mediates tubulin polyglutamylation which induces establishment of microtubule heterogeneity in sperm flagella, thereby playing a role in normal motile flagella axoneme structure and sperm flagella beating pattern (PubMed:27257088).|||cilium basal body|||cytoskeleton|||flagellum axoneme http://togogenome.org/gene/10090:Trim46 ^@ http://purl.uniprot.org/uniprot/D3YXA6|||http://purl.uniprot.org/uniprot/Q7TNM2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Expressed in the central nervous system, including pyramidal neurons and interneurons in the cortex and hippocampus and all neuronal cell types in the cerebral and cerebellar cortex, and in the peripheral nervous system, including the dorsal root ganglion neurons.|||Interacts with TUBB3 and TUBA4A.|||Microtubule-associated protein that is involved in the formation of parallel microtubule bundles linked by cross-bridges in the proximal axon. Required for the uniform orientation and maintenance of the parallel microtubule fascicles, which are important for efficient cargo delivery and trafficking in axons. Thereby also required for proper axon formation, the establishment of neuronal polarity and proper neuronal migration.|||axon|||cytoskeleton http://togogenome.org/gene/10090:Baz1a ^@ http://purl.uniprot.org/uniprot/G3UWZ0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Aldoa ^@ http://purl.uniprot.org/uniprot/A6ZI44|||http://purl.uniprot.org/uniprot/P05064|||http://purl.uniprot.org/uniprot/Q5FWB7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I fructose-bisphosphate aldolase family.|||Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis (By similarity). In addition, may also function as scaffolding protein (By similarity).|||Homotetramer. Interacts with SNX9 and WAS. Interacts with FBP2; the interaction blocks FBP2 inhibition by physiological concentrations of AMP and reduces inhibition by Ca(2+) (By similarity).|||I band|||In vertebrates, three forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.|||M line http://togogenome.org/gene/10090:Lysmd4 ^@ http://purl.uniprot.org/uniprot/Q8CC84 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Mturn ^@ http://purl.uniprot.org/uniprot/A0A087WQV4|||http://purl.uniprot.org/uniprot/Q8CGA4 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MTURN family.|||Cytoplasm|||Expressed in embryo throughout the early nervous system. Strongly expressed in differentiating neurons in the brain, spinal cord and retina. Not detected in the lens at any developmental stage tested.|||Expressed in the thymus, bone marrow and spleen.|||Phosphorylation at Tyr-34 is essential for its ability to promote megakaryocyte differentiation.|||Promotes megakaryocyte differentiation by enhancing ERK and JNK signaling as well as up-regulating RUNX1 and FLI1 expression (PubMed:24681962). Represses NF-kappa-B transcriptional activity by inhibiting phosphorylation of RELA at 'Ser- 536' (By similarity). May be involved in early neuronal development (By similarity). http://togogenome.org/gene/10090:Vmn1r167 ^@ http://purl.uniprot.org/uniprot/G3UW71 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Vbp1 ^@ http://purl.uniprot.org/uniprot/P61759 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prefoldin subunit alpha family.|||Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins (By similarity).|||Cytoplasm|||Heterohexamer of two PFD-alpha type and four PFD-beta type subunits. Binds to the C-terminal part of VHL.|||Nucleus http://togogenome.org/gene/10090:Or10am5 ^@ http://purl.uniprot.org/uniprot/Q7TQV1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptprz1 ^@ http://purl.uniprot.org/uniprot/B2RXS8|||http://purl.uniprot.org/uniprot/B9EKR1|||http://purl.uniprot.org/uniprot/Q8C4M8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the alpha-carbonic anhydrase family.|||Belongs to the protein-tyrosine phosphatase family. Receptor class 5 subfamily.|||Cell membrane|||Detected in neurons and astrocytes in the central nervous system (CNS). Detected in the hippocampus and in brain cortex.|||Membrane|||No visible phenotype. Mice are born at the expected Mendelian rate, are viable and fertile (PubMed:11003666). Embryonic mutant mice show increased levels of oligodendrocyte precursor cells in the spinal cord, combined with impaired differentiation of the precursor cells into mature, fully myelinating oligodendrocytes (PubMed:21969550). Mutant mice show slightly increased susceptibility to experimental autoimmune encephalomyelitis (EAE) and strongly reduced recovery. Contrary to wild-type, mutant mice remain paralyzed and display increased levels of apoptotic oligodendrocytes in the spinal cord (PubMed:12355066). Besides, mutant mice display impaired contextual fear memory, probably due to impaired dephosphorylation of proteins that are part of important signaling cascades (PubMed:16513268).|||Protein tyrosine phosphatase that negatively regulates oligodendrocyte precursor proliferation in the embryonic spinal cord. Required for normal differentiation of the precursor cells into mature, fully myelinating oligodendrocytes. May play a role in protecting oligondendrocytes against apoptosis. May play a role in the establishment of contextual memory, probably via the dephosphorylation of proteins that are part of important signaling cascades.|||Secreted|||The carbonic-anhydrase like domain interacts with CNTN1 (contactin) (PubMed:20133774, PubMed:21969550). Interaction with PTN promotes formation of homooligomers; oligomerization impairs phosphatase activity (By similarity). Interacts (via chondroitin sulfate chains) with MDK (via C-terminal); this interaction is inhibited by PTN; this interaction promotes neuronal migration (By similarity). http://togogenome.org/gene/10090:Opn1mw ^@ http://purl.uniprot.org/uniprot/O35599|||http://purl.uniprot.org/uniprot/Q3UEX0 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Cell membrane|||Expressed in retina (at protein level) (PubMed:30948514). Expressed in cone photoreceptor cells (at protein level) (PubMed:11055434).|||Expressed in the retinal outer nuclear layer and the inner nuclear layer at postnatal day 10.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Monomer. Homodimer. Homotetramer.|||N-glycosylated (PubMed:30948514). O-glycosylated (PubMed:30948514).|||Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.|||Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal. May increase spectral sensitivity in dim light. http://togogenome.org/gene/10090:Pgd ^@ http://purl.uniprot.org/uniprot/Q9DCD0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 6-phosphogluconate dehydrogenase family.|||Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Cluh ^@ http://purl.uniprot.org/uniprot/A0A0R4J140|||http://purl.uniprot.org/uniprot/Q5SW19 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CLU family.|||Cytoplasm|||Cytoplasmic granule|||mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria. Specifically binds mRNAs of nuclear-encoded mitochondrial proteins in the cytoplasm and regulates transport or translation of these transcripts close to mitochondria, playing a role in mitochondrial biogenesis. http://togogenome.org/gene/10090:Rab22a ^@ http://purl.uniprot.org/uniprot/P35285 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Binds EEA1 (By similarity). Interacts (in its GTP-bound form) with RINL (By similarity). Interacts directly with ZFYVE20 (PubMed:16034420). Interacts (in its GTP-bound form) with RABGEF1 (PubMed:19759177).|||Cell membrane|||Cytoplasmic vesicle|||Detected in brain and heart, and at lower levels in lung and spleen.|||Early endosome|||Endosome membrane|||Late endosome|||Plays a role in endocytosis and intracellular protein transport (PubMed:19759177, PubMed:27718357). Mediates trafficking of TF from early endosomes to recycling endosomes. Required for NGF-mediated endocytosis of NTRK1, and subsequent neurite outgrowth. Binds GTP and GDP and has low GTPase activity. Alternates between a GTP-bound active form and a GDP-bound inactive form (By similarity).|||phagosome|||phagosome membrane|||ruffle http://togogenome.org/gene/10090:Gpr180 ^@ http://purl.uniprot.org/uniprot/Q8BPS4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Smim18 ^@ http://purl.uniprot.org/uniprot/J3QNP2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Snx17 ^@ http://purl.uniprot.org/uniprot/Q8BVL3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sorting nexin family.|||Critical regulator of endosomal recycling of numerous surface proteins, including integrins, signaling receptor and channels (PubMed:12169628, PubMed:16052210). Binds to NPxY sequences in the cytoplasmic tails of target cargos (By similarity). Associates with retriever and CCC complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGB1, ITGB5 and their associated alpha subunits (By similarity). Also required for maintenance of normal cell surface levels of APP and LRP1 (PubMed:16052210, PubMed:18276590). Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) (By similarity).|||Cytoplasm|||Cytoplasmic vesicle membrane|||Detected in brain neurons (at protein level). Broadly expressed, with highest levels in brain and placenta, and lowest levels in colon, intestine and liver.|||Early endosome|||Monomer (By similarity). Interacts with APP (via cytoplasmic YXNPXY motif) (PubMed:18276590). Interacts with KIF1B (PubMed:19967056). Interacts with the C-termini of P-selectin, PTC, LDLR, VLDLR, LRP1 and LRP8. Interacts with KRIT1 (via N-terminus) (PubMed:12169628, PubMed:16052210). Interacts with HRAS. Interacts with ITGB1 and ITGB5 (via NPxY motif). Interacts with CCDC22, CCDC93, VPS26C and VPS35L; the interaction with VPS26C is direct and associates SNX17 with the retriever and CCC complexes (By similarity).|||The PTB-like F3 module within the FERM-like domain mediates cargo recognition via their NPxY sequences, while the F1 module (Ras-associating) is responsible for interaction with membrane-bound HRAS.|||The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)). Required for association with endosomes. http://togogenome.org/gene/10090:Sorbs3 ^@ http://purl.uniprot.org/uniprot/Q9R1Z8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell junction|||Interacts with vinculin by the first two SH3 domains and the proline rich region of vinculin. Binds to SOS (guanine nucleotide exchange factor of RAS and RAC), through its third SH3 domain. The formation of this complex is down-regulated by phosphorylation of SOS. Interacts with SAFB2, INPPL1/SHIP2 and SRCIN1 (By similarity). Interacts with DLG5 through its third SH3 domain. Interacts with SOCS7 and MAPK1/ERK2. Interacts with FASLG (By similarity).|||Phosphorylated at Ser-594 by MAPK1/ERK2 during cell spreading.|||Promotes up-regulation of actin stress fiber formation.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Kcnv2 ^@ http://purl.uniprot.org/uniprot/Q8CFS6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. V (TC 1.A.1.2) subfamily. Kv8.2/KCNV2 sub-subfamily.|||Cell membrane|||Heteromultimer with KCNB1, KCNC1 and KCNF1. Does not form homomultimers (By similarity).|||Potassium channel subunit. Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values (By similarity).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Ift122 ^@ http://purl.uniprot.org/uniprot/Q6NWV3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is required in ciliogenesis and ciliary protein trafficking (By similarity). Involved in cilia formation during neuronal patterning. Acts as a negative regulator of Shh signaling. Required to recruit TULP3 to primary cilia (PubMed:19000668, PubMed:21209331).|||Component of the IFT complex A (IFT-A) complex. IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts with IFT43:WDR35; the interaction connects the 2 IFT-A subcomplexes. Interacts with IFTAP; the interaction associates IFTAP with IFT-A complex.|||Embryonic lethal (manifesting between 11.5 dpc and 13.5 dpc). Multiple developmental defects (exencephaly, situs viscerum inversus, delay in turning, hemorrhage and defects in limb development). In the node, primary cilia are absent or malformed in homozygous mutant and heterozygous embryos, respectively. The Shh signaling pathway is impaired in both neural tube patterning (expansion of motoneurons and rostro-caudal level-dependent contraction or expansion of the dorso-lateral interneurons) and limb patterning (ectrosyndactyly). The proteolytic processing of Gli3 is altered. Defects in Ift122 are the cause of the sister of open brain (sopb) phenotype, a mutant that induces embryonic lethality and generates primary cilia with features of defective retrograde intraflagellar transport.|||Expression at least from 7.5 dpc onwards throughout embryonic development with lower levels at 7.5 dpc and 9.5 dpc. Ubiquitously expressed at 11.5 dpc.|||Forms the trimeric core subcomplex IFT122:IFT140:WDR19 via the C-terminal region, whereas it interacts with IFT43:WDR35 via the N-terminal region containing the WD repeats.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Krt42 ^@ http://purl.uniprot.org/uniprot/Q6IFX2 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Expressed in nail matrix and nail bed epithelium (at protein level). Also expressed in tongue and digits with weak expression in vibrissae and in both filiform and fungiform papillae of oral mucosa.|||Heterodimer of a type I and a type II keratin. Colocalizes with KRT8/KRT18 filament network.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Mrc2 ^@ http://purl.uniprot.org/uniprot/Q64449 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ C-type lectin domains 3 to 8 are not required for calcium-dependent binding of mannose, fucose and N-acetylglucosamine. C-type lectin domain 2 is responsible for sugar-binding in a calcium-dependent manner (By similarity).|||Fibronectin type-II domain mediates collagen-binding.|||Highly expressed at day 7 of embryonic development and detected throughout the later stages of embryonic development.|||Highly expressed in heart, lung and kidney, but little or no expression in brain, thymus or adult liver. Expressed at highly endothelialized sites such as those in choroid plexus and kidney glomerulai as well as in chondrocytes in cartilaginous regions of the embryo.|||Interacts directly with PLAUR/UPAR and PLAU/pro-UPA to form a tri-molecular complex. Interacts with collagen V and with C-terminal region of type I collagen/COL1A1 (By similarity).|||May play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity. Internalizes glycosylated ligands from the extracellular space for release in an endosomal compartment via clathrin-mediated endocytosis. May be involved in plasminogen activation system controlling the extracellular level of PLAUR/PLAU, and thus may regulate protease activity at the cell surface. May contribute to cellular uptake, remodeling and degradation of extracellular collagen matrices. May participate in remodeling of extracellular matrix cooperating with the matrix metalloproteinases (MMPs).|||Membrane|||Mice show impaired mammary tumor growth. Tumors from mice lacking Mrc2 display an abrogation of cellular collagen uptake, a fibrotic state characterized by the accumulation of both basement membrane and interstitial collagens, and an overall tumor size reduction, despite the collagen accumulation. Fibroblasts from mice lacking Mrc2 display a severe impairment of internalization of collagen IV and V and thus, exhibit a general deficiency in uptake and delivery of collagens to vesicular compartments. Fibroblasts also have diminished initial adhesion to collagen as well as impaired migration on fibrillar collagen. Mice with a targeted deletion of Mrc2 exon 2-6 are phenotypically normal, healthy and fertile. This deletion resulted in expression of a protein that lacks the ricin B-type lectin domain, the fibronectin type-II domain and the first C-type lectin domain. Fibroblasts from these mice display C-type lectin activity, but have a defect in collagen-binding and internalization, and an impaired migratory phenotype.|||Phosphorylated.|||Ricin B-type lectin domain contacts with the second C-type lectin domain. http://togogenome.org/gene/10090:Sephs2 ^@ http://purl.uniprot.org/uniprot/P97364 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the selenophosphate synthase 1 family. Class I subfamily.|||Binds 1 Mg(2+) ion per subunit.|||Homodimer.|||Synthesizes selenophosphate from selenide and ATP.|||Truncated SEPHS2 proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(KLHDC3) complex, which recognizes the glycine (Gly) at the C-terminus of truncated SEPHS2 proteins. http://togogenome.org/gene/10090:Wfikkn1 ^@ http://purl.uniprot.org/uniprot/Q8R0S6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WFIKKN family.|||Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease- and metalloprotease-inhibitor activity (By similarity).|||Secreted|||The second BPTI/Kunitz inhibitor domain is able to inhibit trypsin. It has however no activity toward chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator (By similarity). http://togogenome.org/gene/10090:Tmem268 ^@ http://purl.uniprot.org/uniprot/Q8R239 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or8c16 ^@ http://purl.uniprot.org/uniprot/Q9EQB2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hmgn3 ^@ http://purl.uniprot.org/uniprot/Q9DCB1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HMGN family.|||Binds to nucleosomes, regulating chromatin structure and consequently, chromatin-dependent processes such as transcription, DNA replication and DNA repair. Affects both insulin and glucagon levels and modulates the expression of pancreatic genes involved in insulin secretion. Regulates the expression of the glucose transporter SLC2A2 by binding specifically to its promoter region and recruiting PDX1 and additional transcription factors. Regulates the expression of SLC6A9, a glycine transporter which regulates the glycine concentration in synaptic junctions in the central nervous system, by binding to its transcription start site. May play a role in ocular development and astrocyte function.|||Expressed in the brain, eye, prostate, thyroid, kidney, testis, glial cells and insulin-producing cells of the Langerhans pancreatic islets. In the brain, expressed in the lateral olfactory tract, anterior commissure, corpus callosum, internal capsule, fornix, stria medullans, optic tract, axon bundles, Purkinje cell layer and granular layer of the cerebellum. In retina, expressed in the nuclei of cells in the inner nuclear layer including amacrine, bipolar and horizontal neurons and in the nuclei of ganglion neurons. Detected at low levels in the liver.|||Interacts with the ligand binding domain of the thyroid receptor (TR) (in vitro). Requires the presence of thyroid hormone for its interaction. Interacts with transcriptional regulator SEHBP. Interacts with nucleosomes.|||Mice are viable and fertile. Mice have a mild diabetic phenotype and lower plasma glucagon levels. The overall shape of the islets, the location of the alpha cells in the mantle of the pancreatic islets or proliferation of pancreatic alpha cells are not affected.|||Nucleus|||Transiently expressed in the stroma and endothelium of the cornea at birth. Subsequently expressed in the corneal epithelium and the inner nuclear and ganglion cell layers of the retina. The predominant form in developing ocular tissues is isoform 2, although isoform 1 is also detectable. http://togogenome.org/gene/10090:Chrm1 ^@ http://purl.uniprot.org/uniprot/P12657 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM1 sub-subfamily.|||Cell membrane|||Interacts with GPRASP2 (By similarity). Interacts with TMEM147 (By similarity).|||Postsynaptic cell membrane|||The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover. http://togogenome.org/gene/10090:Cox5a ^@ http://purl.uniprot.org/uniprot/P12787 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 5A family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Interacts with AFG1L (By similarity). Interacts with RAB5IF (By similarity).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lpo ^@ http://purl.uniprot.org/uniprot/Q5SW46 ^@ Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peroxidase family.|||Binds 1 Ca(2+) ion per heterodimer.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.|||Cytoplasm|||Expressed in the colon, including colonocytes and mucin-containing goblet cells (PubMed:22343415, PubMed:34127712). Not detected in the ileum (PubMed:22343415).|||Heme-containing oxidoreductase which catalyzes the conversion of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid (OSCN(-)) in the presence of hydrogen peroxide (H2O2) (By similarity). Also involved in the conversion of iodide (I(-)) into hypoiodite (IO(-)) in the presence of H2O2 (By similarity). Responsible for the inactivation of a wide range of micro-organisms and hence, important component of defense mechanism (By similarity). May be implicated in airway host defense against infection (By similarity). May contribute to maintaining an appropriate H2O2 cellular level, therefore protecting cells from H2O2-caused injuries and inflammation (PubMed:34127712).|||Knockout mice exhibit inflammation and lesions in the cardiovascular, respiratory, digestive or excretory systems, neuropathology, and tumors, with high incidence.|||Secreted|||Thiocyanate (SCN(-)) and hypothiocyanite (OSCN(-)) are bound in the distal heme cavity. The iodide ion (I(-)) occupies a position which is stabilized by the interactions with heme moiety, His-224, Arg-370 and Glu-373. Hydrogen peroxide is held between the heme iron and His-224. http://togogenome.org/gene/10090:Folh1 ^@ http://purl.uniprot.org/uniprot/O35409|||http://purl.uniprot.org/uniprot/Q0VDM6 ^@ Activity Regulation|||Caution|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.|||Belongs to the peptidase M28 family. M28B subfamily.|||Binds 2 Zn(2+) ions per subunit. Required for NAALADase activity.|||Cell membrane|||Expressed predominantly in the hippocampal region of the brain and in kidney. Lower levels in the ovary, testis and mandibular gland.|||Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides (By similarity). In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate.|||Homodimer.|||Membrane|||The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal.|||The NAALADase and folate hydrolase activities are inhibited by quisqualic acid.|||There are amino acid differences between the sequence shown in fig.1 (PubMed:11210180) and the sequence deposited in the database (AF026380). The sequence from fig.1 shows only 3 conflicts between PubMed:11210180 and PubMed:16141072. These are at AA positions 141, 240 and 287. http://togogenome.org/gene/10090:Bltp3b ^@ http://purl.uniprot.org/uniprot/A2RSJ4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Early endosome|||Homodimer (via N-terminus). Associates with the Golgi-associated retrograde protein (GARP) complex. Interacts with GARP complex component VPS52. Interacts (via C-terminal coiled-coil domain) with STX6.|||Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites. Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex.|||cytosol http://togogenome.org/gene/10090:Tubb5 ^@ http://purl.uniprot.org/uniprot/P99024 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin family.|||Heterodimer of alpha and beta chains (By similarity). A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with CIMAP3 (PubMed:20643351). Interacts with DIAPH1 (By similarity). Interacts with MX1 (By similarity). May interact with RNABP10 (PubMed:18347012). Interacts with CFAP157 (PubMed:27965440). Nascent tubulin polypeptide interacts (via beta-tubulin MREI motif) with TTC5/STRAP; this interaction results in tubulin mRNA-targeted degradation (By similarity).|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Results in a perturbation of the cell cycle of neurogenic progenitors as well as an alteration in the position of migrating neurons. There is a decrease in neurons in the cortical plate and an accumulation of cells within the ventricular and intermediate zones.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Ubiquitously expressed with highest levels in spleen, thymus and immature brain. Expressed in embryonic brain, including throughout the developing cortex and in the subventricular zone. Also found in radial glial cells, intermediate progenitors, migrating neurons and postmitotic neurons (PubMed:23246003). Expressed in skin and developing hair follicle (PubMed:26637975).|||cytoskeleton http://togogenome.org/gene/10090:Or2z2 ^@ http://purl.uniprot.org/uniprot/Q8VGD8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc44a4 ^@ http://purl.uniprot.org/uniprot/Q3TL93|||http://purl.uniprot.org/uniprot/Q3ULA4|||http://purl.uniprot.org/uniprot/Q91VA1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the CTL (choline transporter-like) family.|||Cell membrane|||Choline transporter that plays a role in the choline-acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury (By similarity). Also described as a thiamine pyrophosphate transporter in colon, may mediate the absorption of microbiota-generated thiamine pyrophosphate and contribute to host thiamine (vitamin B1) homeostasis (PubMed:24379411).|||Choline transporter.|||Expressed in colon and cecum.|||Membrane|||N-glycosylated; N-glycosylation of Asn-67 and Asn-391 is required for a proper thiamine pyrophosphate uptake. http://togogenome.org/gene/10090:Dsg2 ^@ http://purl.uniprot.org/uniprot/O55111 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.|||Expressed in embryo at 7 to 17 dpc. Expressed uniformly in all 12.5 dpc epithelia, gradually becoming confined to the basal cell layers during.|||Expressed in epidermis, heart, brain, spleen, lung, liver skeletal muscle, kidney and testis.|||Interacts with PKP2.|||Palmitoylated by ZDHHC5 at the plasma membrane.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Mrpl14 ^@ http://purl.uniprot.org/uniprot/Q9D1I6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL14 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Interacts with MALSU1.|||May form part of 2 intersubunit bridges in the assembled ribosome. Upon binding to MALSU1, intersubunit bridge formation is blocked, preventing ribosome formation and repressing translation.|||Mitochondrion http://togogenome.org/gene/10090:Hdac6 ^@ http://purl.uniprot.org/uniprot/Q3UG37|||http://purl.uniprot.org/uniprot/Q9Z2V5 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the histone deacetylase family. HD type 2 subfamily.|||Binds 3 Zn(2+) ions per subunit.|||Cytoplasm|||Expressed in neurons of the cortex. Expressed in Purkinje cells. Detected in keratinocytes (at protein level).|||Interacts with SIRT2 (via both phosphorylated, unphosphorylated, active or inactive forms); the interaction is necessary for the complex to interact with alpha-tubulin (By similarity). Under proteasome impairment conditions, interacts with UBD via its histone deacetylase 1 and UBP-type zinc-finger regions (By similarity). Interacts with BBIP1, CBFA2T3, CYLD, DDIT3/CHOP, ZMYND15, F-actin and HDAC11 (PubMed:11533236, PubMed:19893491, PubMed:20675388). Interacts with RIPOR2; this interaction occurs during early myogenic differentiation and prevents HDAC6 to deacetylate tubulin (By similarity). Interacts with AURKA; AURKA-mediated phosphorylation of HDAC6 promotes deacetylation of alpha-tubulin (By similarity). Interacts with DYSF; this interaction occurs during early myogenic differentiation (By similarity). Interacts with TPPP; inhibiting the tubulin deacetylase activity of HDAC6 (By similarity). Interacts with DYNLL1 (By similarity). Interacts with ATP13A2; the interaction results in recruitment of HDAC6 to lysosomes to promote CTTN deacetylation (By similarity). Interacts with CCDC141 (via the N-terminal region); inhibiting the deacetylase activity of HDAC6 (PubMed:27737934). Interacts with IPO7; the interaction facilitates HDAC6 nuclear translocation in dental papilla cells (PubMed:35922041).|||Nucleus|||Perikaryon|||Phosphorylated by AURKA; phosphorylation increases HDAC6-mediated deacetylation of alpha-tubulin and subsequent disassembly of cilia.|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:9891014). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:9891014). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:9891014). In addition to histones, deacetylates other proteins: plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin (PubMed:19893491, PubMed:27737934). Required for cilia disassembly; via deacetylation of alpha-tubulin (By similarity). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (By similarity). Promotes odontoblast differentiation following IPO7-mediated nuclear import and subsequent repression of RUNX2 expression (PubMed:35922041). In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome (By similarity). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy (PubMed:22819792).|||Sumoylated in vitro.|||Ubiquitinated. Its polyubiquitination however does not lead to its degradation.|||axon|||centrosome|||cilium|||cilium basal body|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Prss29 ^@ http://purl.uniprot.org/uniprot/Q99MS4 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Expressed in embryos and placenta. Found in uterus especially in glandular epithelium during zona lysis and implantation.|||Highly expressed from 6.5 dpc plus deciduum. Also expressed, but to a lower extent, in placenta from 11.5 dpc and 13.5 dpc. Not expressed at 8.5 dpc and 11.5 dpc in embryo proper. Expressed at 4.0 dpc in uterus.|||Homooligomer, heterodimer and heterotetramer. Able to form homo- and hetero- tetrameric structures. Heterotetramer is far more stable than the homotetramer.|||Involved in embryo hatching and implantation.|||Secreted|||Up-regulated in uterine endometrial glands following the initiation of embryo implantation. By progesterone. http://togogenome.org/gene/10090:Krtap20-2 ^@ http://purl.uniprot.org/uniprot/E9Q0A8 ^@ Function|||Subunit ^@ In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:G0s2 ^@ http://purl.uniprot.org/uniprot/Q545U0|||http://purl.uniprot.org/uniprot/Q61585 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Directly interacts with BCL2; this interaction prevents the formation of the anti-apoptotic BAX-BCL2 complex.|||Mitochondrion|||Promotes apoptosis by binding to BCL2, hence preventing the formation of protective BCL2-BAX heterodimers. http://togogenome.org/gene/10090:Lelp1 ^@ http://purl.uniprot.org/uniprot/Q9DAE3 ^@ Similarity ^@ Belongs to the cornifin (SPRR) family. http://togogenome.org/gene/10090:Tmem67 ^@ http://purl.uniprot.org/uniprot/Q8BR76 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ A spontaneous deletion of TMEM67 cause the bilateral polycystic kidneys (bpck) phenotype, a disease mimicking human Meckel-Gruber syndrome 3. Homozygous bpck/bpck mice typically manifest bilateral nephropathy with swollen abdomens resulting from grossly enlarged polycystic kidneys and die by 3 week of age. Some mice also develop hydrocephalus, usually detectable within a few days of birth (PubMed:19211713). Additionally, bpck/bpck mice exhibit retinal degeneration and tissue disorganization in the eye, and cochlear defects (PubMed:23393159).|||Cell membrane|||Endoplasmic reticulum membrane|||Homodimer (By similarity). Part of the tectonic-like complex (also named B9 complex) (PubMed:21725307). Interacts with DNAJB9, DNAJC10 and mutated SFTPC (By similarity). Interacts with SYNE2 during the early establishment of cell polarity (By similarity). Interacts (via C-terminus) with FLNA (By similarity). Interacts with TMEM218 (By similarity). Interacts with WNT5A (By similarity). Interacts with ROR2 (By similarity).|||Knockout mice die soon after birth. They show multi-organ developmental abnormalities including pulmonary hypoplasia, ventricular septal defects, shortening of the body longitudinal axis, limb abnormalities, and cochlear hair cell stereociliary bundle orientation and basal body/kinocilium positioning defects (PubMed:26035863).|||Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. Involved in centrosome migration to the apical cell surface during early ciliogenesis. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Is a key regulator of stereociliary bundle orientation (PubMed:26035863). Required for epithelial cell branching morphology (PubMed:26035863). Essential for endoplasmic reticulum-associated degradation (ERAD) of surfactant protein C (sftpc). Involved in the negative regulation of canonical Wnt signaling, and activation of the non-canonical cascade stimulated by WNT5A (PubMed:26035863). In non-canonical Wnt signaling, it may act as ROR2 coreceptor (PubMed:26035863).|||cilium basal body http://togogenome.org/gene/10090:Vmn1r220 ^@ http://purl.uniprot.org/uniprot/Q8R272 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bmp7 ^@ http://purl.uniprot.org/uniprot/P23359 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis (PubMed:9013703, PubMed:22461901). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2A. Once all three components are bound together in a complex at the cell surface, ACVR2A phosphorylates and activates ACVR1. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. For specific functions such as growth cone collapse in developing spinal neurons and chemotaxis of monocytes, uses also BMPR2 as type II receptor. Can also signal through non-canonical pathways such as P38 MAP kinase signaling cascade that promotes brown adipocyte differentiation through activation of target genes, including members of the SOX family of transcription factors (By similarity). Promotes the expression of HAMP, this is repressed by its interaction with ERFE (PubMed:30097509).|||Homodimer; disulfide-linked (By similarity). Interacts with SOSTDC1 (PubMed:14623234). Interacts with TWSG1 (PubMed:15843411). Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity). Interacts with type I receptor ACVR1 (By similarity). Interacts with type II receptor ACVR2A (By similarity). Interacts with NOG; this interaction inhibits canonical BMP signaling (By similarity). Interacts with SCUBE3 (By similarity). Interacts with ERFE; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509).|||Secreted|||nullDeltion mutant mice die shortly after birth and display developmental defects in kidney, eye, skull, ribcage, and hind limbs. They also show defects in the development of the axial skeleton from the skull to the tail and the ossification of bones. http://togogenome.org/gene/10090:Rpl22l1 ^@ http://purl.uniprot.org/uniprot/Q0VBA4|||http://purl.uniprot.org/uniprot/Q9D7S7 ^@ Similarity ^@ Belongs to the eukaryotic ribosomal protein eL22 family. http://togogenome.org/gene/10090:Nherf1 ^@ http://purl.uniprot.org/uniprot/P70441|||http://purl.uniprot.org/uniprot/Q3TG37 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Cytoplasm|||Endomembrane system|||Expressed in spermatogenic cells.|||Homodimer, and heterodimer with NHERF2. Binds the N-termini of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2 and NOS2. Binds ARHGAP17, EPI64, RACK1, OPRK1, GNAQ, CTNNB1, PLCB3 and CLCN3. Forms a complex with CFTR and SLC4A7. Forms a complex with SLC4A7 and ATP6V1B1 (By similarity). Binds PDZK1. Binds the C-terminus of PAG1. In resting T-cells, part of a PAG1-NHERF1-MSN complex which is disrupted upon TCR activation. Directly interacts with HTR4. Interacts with MCC (By similarity). Interacts with TRPC4 (via the PDZ-binding domain) (By similarity). Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is not detected in glomerular epithelium cells (By similarity). Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-binding motif DTHL); the interaction take place early in the secretory pathway and is necessary for its apical membrane sorting (By similarity). Interacts with SLC34A1 (By similarity). Interacts with CFTR, SLC26A3 and SLC26A6. Interacts (via PDZ domains) with ACE2 (via PDZ-binding motif); the interaction may enhance ACE2 membrane residence (By similarity).|||Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression.|||Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling (By similarity). May participate in HTR4 targeting to microvilli. Involved in the regulation of phosphate reabsorption in the renal proximal tubules (By similarity). Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa.|||filopodium|||microvillus|||ruffle http://togogenome.org/gene/10090:Zscan12 ^@ http://purl.uniprot.org/uniprot/Q6ZQB8|||http://purl.uniprot.org/uniprot/Q8C6D3|||http://purl.uniprot.org/uniprot/Q9Z1D7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus|||Testis specific. http://togogenome.org/gene/10090:Tprn ^@ http://purl.uniprot.org/uniprot/A2AI08 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the taperin family.|||Expressed in the sensory epithelia of the organ of Corti and vestibular end organs and, to a lesser extent, in Reisner's membrane and the spiral ligament (at protein level). At postnatal day 2, expression is detected in cochlea, liver, brain, kidney, heart and lung.|||stereocilium http://togogenome.org/gene/10090:Tlr7 ^@ http://purl.uniprot.org/uniprot/P58681|||http://purl.uniprot.org/uniprot/Q548J0 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by guanosine analogs including deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA-independent manner.|||Belongs to the Toll-like receptor family.|||Contains two binding domains, first site for small ligands and second site for ssRNA.|||Endoplasmic reticulum membrane|||Endosomal receptor that plays a key role in innate and adaptive immunity. Controls host immune response against pathogens through recognition of uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analogs (PubMed:21402738). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction. In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively (PubMed:14976261) (By similarity).|||Endosome membrane|||Homodimer (By similarity). Interacts with MYD88 via their respective TIR domains (Probable). Interacts with UNC93B1 (PubMed:17452530). Interacts with SMPDL3B (PubMed:26095358).|||Lysosome|||Membrane|||The first cleavage is performed by asparagine endopeptidase or cathepsin family members. This initial cleavage event is followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling.|||phagosome http://togogenome.org/gene/10090:Cntn1 ^@ http://purl.uniprot.org/uniprot/P12960 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. Contactin family.|||Cell membrane|||Contactins mediate cell surface interactions during nervous system development. Involved in the formation of paranodal axo-glial junctions in myelinated peripheral nerves and in the signaling between axons and myelinating glial cells via its association with CNTNAP1. Participates in oligodendrocytes generation by acting as a ligand of NOTCH1. Its association with NOTCH1 promotes NOTCH1 activation through the released notch intracellular domain (NICD) and subsequent translocation to the nucleus. Interaction with TNR induces a repulsion of neurons and an inhibition of neurite outgrowth.|||Expressed in the ovary and in Sertoli cells of the testis.|||F3 shares with L1, N-CAM, MAG, and other cell adhesion molecules from nervous tissue the L2/HNK-1 carbohydrate epitope.|||Monomer. Interacts with CNTNAP1 in cis form (By similarity). Binds to the carbonic-anhydrase like domain of PTPRZ1 (PubMed:20133774). Interacts with NOTCH1 and TNR (PubMed:7678967, PubMed:14567914). Detected in a complex with NRCAM and PTPRB (PubMed:11564762). Interacts with TASOR (PubMed:31112734). http://togogenome.org/gene/10090:Vdac2 ^@ http://purl.uniprot.org/uniprot/Q60930 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic mitochondrial porin family.|||Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands.|||Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules (By similarity). The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (By similarity). The open state has a weak anion selectivity whereas the closed state is cation-selective (By similarity). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (By similarity). Binding of ceramide promotes the Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (By similarity).|||Highest levels of expression detected in testis, less but still abundant expression in heart, kidney, brain, and skeletal muscle (PubMed:8660977). Expressed in the sperm midpiece (at protein level) (PubMed:33087875).|||Interacts with hexokinases (By similarity). Interacts with ARMC12 in a TBC1D21-dependent manner (PubMed:33536340). Interacts with KLC3 (PubMed:22561200). Interacts with SPATA33 (PubMed:34446558, PubMed:33087875). Interacts with PPP3CC in a SPATA33-dependent manner (PubMed:34446558).|||Membrane|||Mitochondrion outer membrane|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Atp8b2 ^@ http://purl.uniprot.org/uniprot/E9QAL4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Membrane http://togogenome.org/gene/10090:Pip4k2a ^@ http://purl.uniprot.org/uniprot/O70172 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Has both ATP- and GTP-dependent kinase activities. May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2 (By similarity). May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation (By similarity). Required for lysosome-peroxisome membrane contacts and intracellular cholesterol transport through modulating peroxisomal PtdIns(4,5)P2 level (By similarity). In collaboration with PIP4K2B, has a role in mediating autophagy in times of nutrient stress (PubMed:29727621). Required for autophagosome-lysosome fusion and the regulation of cellular lipid metabolism (PubMed:29727621). Negatively regulates insulin signaling through a catalytic-independent mechanism. PIP4Ks interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (By similarity). May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size (PubMed:16434494).|||Cell membrane|||Cytoplasm|||Detected in rod photoreceptor cells.|||Homodimer. Interacts with PIP4K2B; the interaction may regulate localization to the nucleus (By similarity). Probably interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase activity (By similarity).|||In rod outer segments, activated by light.|||Lysosome|||Nucleus|||Phosphorylated in tyrosines. Phosphorylation is induced by light and increases kinase activity.|||Photoreceptor inner segment|||photoreceptor outer segment http://togogenome.org/gene/10090:H2-M10.1 ^@ http://purl.uniprot.org/uniprot/O19443|||http://purl.uniprot.org/uniprot/Q860W7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Ticam1 ^@ http://purl.uniprot.org/uniprot/Q80UF7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homodimer (By similarity). Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation (PubMed:21703541). Interacts (via TIR domain) with DDX21 (via C-terminus) (PubMed:21703541). Interacts (via TIR domain) with DHX36 (via C-terminus) (PubMed:21703541). Interacts with AZI2 and IRF7 (By similarity). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By similarity). Interacts with TICAM2 in TLR4 recruitment (By similarity). Interaction with PIAS4 inhibits the TICAM1-induced NF-kappa-B, IRF and IFNB1 activation (By similarity). Interacts with IKBKB and IKBKE (By similarity). Interaction with SARM1 blocks TICAM1-dependent transcription factor activation (By similarity). Interacts with TRAF3. Interacts with TRAFD1. Interacts with UBQLN1 (via UBA domain). Interacts with TBK1, TRAF6 and RIPK1 and these interactions are enhanced in the presence of WDFY1 (By similarity). Interacts (via the TIR domain) with TLR3 in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). Interacts with TLR4 in response to poly(I:C) in a WDFY1-dependent manner (PubMed:25736436). Interacts with WDFY1 in response to poly(I:C) (PubMed:25736436). Interacts with TRIM56 (By similarity). Interacts (via the TIR domain) with TLR5 (By similarity). Interacts with TRIM8 (By similarity).|||Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis (PubMed:12855817, PubMed:16002681, PubMed:21703541). Ligand binding to these receptors results in TRIF recruitment through its TIR domain (PubMed:12855817, PubMed:16002681, PubMed:21703541). Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively (PubMed:12855817, PubMed:16002681, PubMed:21703541). Phosphorylation by TBK1 on the pLxIS motif leads to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent immunity against invading pathogens (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines (PubMed:21703541).|||Mice are viable but exhibit abnormalities of the innate immune system.|||Mitochondrion|||Phosphorylated by TBK1. Following activation, phosphorylated by TBK1 at Ser-209 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines.|||Polyubiquitinated at Lys-228 by TRIM38 with 'Lys-48'-linked chains, leading to proteasomal degradation (PubMed:26392463). Polyubiquitinated with 'Lys-6'- and 'Lys-33'-linked chains in a TRIM8-dependent manner; ubiquitination disrupts the interaction with TBK1 and subsequent interferon production (By similarity).|||The N-terminal domain (TRIF-NTD) is globular and consists of two alpha-helical subdomains connected by a 14-residue linker. It shares structural similarity with IFIT family members N-terminal regions.|||The N-terminal region is essential for activation of the IFNB promoter activity.|||The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of TICAM1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines.|||autophagosome|||cytosol http://togogenome.org/gene/10090:Nop56 ^@ http://purl.uniprot.org/uniprot/Q9D6Z1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOP5/NOP56 family.|||Cytoplasm|||Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Part of a large pre-ribosomal ribonucleoprotein (RNP) complex, that consists of at least 62 ribosomal proteins, 45 nonribosomal proteins and both pre-rRNA and mature rRNA species. Within this complex directly interacts with TCOF1 in an RNA-independent manner. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles; the core proteins SNU13, NOP56, NOP58 and FBL assemble stepwise onto the snoRNA. Interacts with NOP1 and NOP58. Interacts with NUFIP1, RUVBL1 and RUVBL2; RUVBL1:RUVBL2 seem to bridge the association of NOP56 with NUFIP1. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Widely expressed, with highest levels in the central nervous system (CNS), including cerebral cortex and cerebellum, and spleen. In the CNS, expressed in Purkinje cells of the cerebellum, as well as in motor neurons of the hypoglossal nucleus and in the spinal cord anterior horn (at protein level).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Jund ^@ http://purl.uniprot.org/uniprot/P15066 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. Jun subfamily.|||Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro) (By similarity). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro) (By similarity).|||Brain and kidney.|||Heterodimer; binds DNA as a heterodimer (By similarity). Component of an AP-1 transcription factor complex composed of JUN-FOS heterodimers (By similarity). As part of the AP-1 transcription factor complex, forms heterodimers with FOS proteins, thereby binding to the AP-1 consensus sequence and stimulating transcription (By similarity). Forms heterodimers with FOSB; thereby binding to the AP-1 consensus sequence (By similarity). Interacts (via MBM motif) with MEN1; this interaction represses transcriptional activation (PubMed:9989505). Interacts with MAPK10; this interaction is inhibited in the presence of MEN1 (By similarity).|||Nucleus|||Phosphorylated by MAP kinases MAPK8 and MAPK10; phosphorylation is inhibited in the presence of MEN1.|||Transcription factor binding AP-1 sites (By similarity). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription factor complex, thereby enhancing its DNA binding activity to an AP-1 consensus sequence 3'-TGA[GC]TCA-5' and enhancing its transcriptional activity (By similarity). http://togogenome.org/gene/10090:Anxa1 ^@ http://purl.uniprot.org/uniprot/P10107|||http://purl.uniprot.org/uniprot/Q4FJV4 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the annexin family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle membrane|||Detected in lung (PubMed:12475898, PubMed:17384087). Detected at the apical membrane of airway epithelial cells (PubMed:17384087). Detected in intestinal epithelial cells (PubMed:18802107). Detected in skeletal muscle (PubMed:14506282). Detected in prostate (PubMed:23727357). Detected in thymus (at protein level) (PubMed:12475898). Detected in stomach, lung, spleen, ovary and uterus, and at lower levels in kidney, thymus and heart (PubMed:12475898).|||Early endosome|||Endosome membrane|||Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Promotes resolution of inflammation and wound healing. Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2.|||Homodimer; non-covalently linked (By similarity). Homodimer; linked by transglutamylation. Homodimers linked by transglutamylation are observed in placenta, but not in other tissues. Interacts with S100A11. Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (By similarity). Interacts with DYSF (PubMed:14506282). Interacts with EGFR (By similarity).|||Lateral cell membrane|||Membrane|||Mice are born at the expected Mendelian rate, appear healthy and are fertile, but tend to die already after about one year. Mutant mice display an increased inflammatory response during zymosan-induced peritonitis, with increased blood leukocyte migration and increased production of IL1B. In mutant mice, glucocorticoid-mediated down-regulation of the early phase of the inflammatory response is abolished, but there is no effect on glucocorticoid-mediated down-regulation of later phases of the inflammatory response. Peritoneal lavage macrophages from mutant mice display decreased phagocytosis. Besides, glucocorticoid-mediated inhibition of phagocytosis is abolished (PubMed:12475898). Mutant mice display increased susceptibility to dextran sulfate sodium (DSS)-induced colitis with increased mucosal injury, slower recovery and increased morbidity (PubMed:18802107). Mutant mice have an exacerbated allergic response after exposure to ovalbumin (PubMed:17948261). T-cells from mutant mice show skewed differentiation into Th1 and Th2 cells with increased differentiation into Th2 cells and decreased differentiation into Th1 cells (PubMed:17948261).|||Nucleus|||Phosphorylated by protein kinase C, EGFR and TRPM7. Phosphorylated in response to EGF treatment.|||Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:12475898). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (PubMed:12475898). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17948261). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17948261). Has no effect on unstimulated T-cells. Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (By similarity). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (By similarity). Plays a role in the formation of phagocytic cups and phagosomes (PubMed:21245195). Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (PubMed:21245195).|||Proteolytically cleaved by cathepsin CTSG to release the active N-terminal peptide Ac2-26.|||Secreted|||Sumoylated.|||The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.|||Up-regulated by the synthetic glucocorticoid fluocinolone acetonide.|||Was originally identified as calcium and phospholipid binding protein that displays Ca(2+)-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.|||cilium|||extracellular exosome|||extracellular space|||phagocytic cup|||secretory vesicle lumen http://togogenome.org/gene/10090:Nexmif ^@ http://purl.uniprot.org/uniprot/Q5DTT1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in the brain, particularly during the late embryonic and perinatal stages of development (PubMed:22531377). In the developing brain, it is expressed only in the cortical plate and subplate region but not in the intermediate or ventricular zone (PubMed:27822498).|||Involved in neurite outgrowth by regulating cell-cell adhesion via the N-cadherin signaling pathway. May act by regulating expression of protein-coding genes, such as N-cadherins and integrin beta-1 (ITGB1).|||Nucleus|||Widely expressed in brain by postmitotic neurons from early development through early adulthood. http://togogenome.org/gene/10090:Serpinb9e ^@ http://purl.uniprot.org/uniprot/O08806 ^@ Similarity ^@ Belongs to the serpin family. Ov-serpin subfamily. http://togogenome.org/gene/10090:Agrp ^@ http://purl.uniprot.org/uniprot/P56473|||http://purl.uniprot.org/uniprot/Q3UU47 ^@ Caution|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in arcuate nucleus and median eminence, adrenal gland (medulla), hypothalamus, testis, and lung.|||Golgi apparatus lumen|||Hypothalamic expression is elevated circa 10-fold in ob/ob and db/db mice.|||Interacts with melanocortin receptors MC3R, MC4R and MC5R.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Plays a role in weight homeostasis. Involved in the control of feeding behavior through the central melanocortin system. Acts as alpha melanocyte-stimulating hormone antagonist by inhibiting cAMP production mediated by stimulation of melanocortin receptors within the hypothalamus and adrenal gland. Has very low activity with MC5R. Is an inverse agonist for MC3R and MC4R being able to suppress their constitutive activity (By similarity). It promotes MC3R and MC4R endocytosis in an arrestin-dependent manner (By similarity).|||Secreted|||The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. http://togogenome.org/gene/10090:Arf5 ^@ http://purl.uniprot.org/uniprot/P84084 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Arf family.|||GTP-binding protein involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.|||Golgi apparatus|||Interacts (when activated) with GGA1, GGA2 and GGA3; the interaction is required for proper subcellular location of GGA1, GGA2 and GGA3 (PubMed:11950392). Binds ASAP2 (By similarity). Interacts with NCS1/FREQ at the Golgi complex. Interacts with RAB11FIP3 and RAB11FIP4 (By similarity).|||Membrane|||Ubiquitous.|||perinuclear region|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gga2 ^@ http://purl.uniprot.org/uniprot/Q6P5E6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GGA protein family.|||Early endosome membrane|||Endosome membrane|||Monomer (By similarity). Interacts with NECAP1, TSG101, UBC and AFTPH/aftiphilin. Interacts with CNST (PubMed:19864490). Interacts with GGA1 and GGA3 (By similarity). Binds to clathrin and activated ARFs, such as ARF1, ARF5 and ARF6 (PubMed:11950392). Binds RABEP1 and RABGEF1. Interacts with the type-I membrane proteins LRP3, M6PR/CD-MPR, IGF2R/CI-MPR and BACE1. Interacts (via N-terminal VHS domain) with SORL1/sorLA and SORT1 (via C-terminal cytosolic domain) (By similarity). Binds the accessory proteins CCDC91, P200, SYNRG, EPN4 and NECAP2. Interacts with ADRA2B. Interacts (via VHS domain) with PIK4B; the interaction is important for PIK4B location at the Golgi apparatus membrane (By similarity).|||Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell surface. Regulates retrograde transport of phosphorylated form of BACE1 from endosomes to the trans-Golgi network.|||The GAE domain binds accessory proteins regulating GGAs function.|||The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis.|||The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif).|||The unstructured hinge region contains clathrin-binding but no autoinhibitory (DXXLL) motifs.|||Ubiquitinated.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gm19668 ^@ http://purl.uniprot.org/uniprot/J3QMD1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Pcdhb6 ^@ http://purl.uniprot.org/uniprot/Q91XZ4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane (PubMed:27161523). Each cadherin domain binds three calcium ions (PubMed:27161523).|||Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination (PubMed:27161523). Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain (PubMed:27161523).|||Cell membrane|||Forms homodimers in trans (molecules expressed by two different cells). Forms promiscuous heterodimers in cis (at the plasma membrane of the same cell) with other protocadherins. http://togogenome.org/gene/10090:Gm20891 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Adgrf2 ^@ http://purl.uniprot.org/uniprot/A0A668KM90|||http://purl.uniprot.org/uniprot/E9Q4J9|||http://purl.uniprot.org/uniprot/Q3UQ38 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Expressed during embryonic development in the skin starting at embryonic day 12 with the formation of the basal layer of the skin.|||Mainly expressed in skin and heart, and very weakly in lung and spleen. Detected in all epidermal layers of skin.|||Membrane|||Most adhesion GPCRs undergo autoproteolysis at the GPS domain. ADGRF2 is not autoproteolyzed at the GPS motif because of the lack of a consensus catalytic triad sequence within GPS domain.|||No visible phenotype.|||Orphan receptor. http://togogenome.org/gene/10090:Tent5a ^@ http://purl.uniprot.org/uniprot/A0A087WS27|||http://purl.uniprot.org/uniprot/D3Z5S8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TENT family.|||Cytoplasm|||Cytoplasmic non-canonical poly(A) RNA polymerase that catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group and participates in the cytoplasmic polyadenylation (PubMed:33882302). Polyadenylates mRNA encoding extracellular matrix constituents and other genes crucial for bone mineralization and during osteoblast mineralization, mainly focuses on ER-targeted mRNAs (PubMed:33882302, PubMed:26803617).|||Expressed in primary osteoblasts derived from neonatal calvaria and osteocytes (PubMed:33882302). Strongly expressed in calvaria and femur (PubMed:26803617).|||Highly expressed in the dental sheet, oral epithelium, and mesenchyme at 12.5 dpc; in the tooth germ bud, ectomesenchyme and oral epithelium at 13.5 dpc; and in the dental papilla and dental epithelium at 14.5 dpc.|||Homozygous mice lacking Tent5a have slightly decreased survival, probably due to perinatal or embryonic lethality, since the effect is already visible at postnatal day 6 (P6). Mutant mice have an abnormal posture with frequent kyphosis and a wavy tail. Mutant mice exhibit frequent bone fractures and newborn mice reveal rib fractures. Adult mutant mice show decreased cartilage ossification of the tail.|||Increased during osteoblast differentiation. http://togogenome.org/gene/10090:Or2q1 ^@ http://purl.uniprot.org/uniprot/Q8VF81 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hoxa4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J193|||http://purl.uniprot.org/uniprot/P06798 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Belongs to the Antp homeobox family. Deformed subfamily.|||During development of the prepuberal testis high levels of HOXA4 transcripts were found at days 17, 24 and 30. The first day of HOXA4 expression was day 14. The activation of the HOXA4 gene in male germ cells seems to occur at the pachytene stage of meiotic prophase and its level of expression is stage-specific during embryogenesis.|||Nucleus|||Overexpression results in abnormal gut development (megacolon).|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to sites in the 5'-flanking sequence of its coding region with various affinities. The consensus sequences of the high and low affinity binding sites are 5'-TAATGA[CG]-3' and 5'-CTAATTTT-3'. http://togogenome.org/gene/10090:Glrx2 ^@ http://purl.uniprot.org/uniprot/Q923X4 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutaredoxin family.|||During development, it is expressed at highest level at 11 dpc.|||Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.|||Mitochondrion|||Monomer; active form. Homodimer; inactive form. The homodimer is probably linked by 1 2Fe-2S cluster (By similarity).|||Nucleus|||The 2Fe-2S present in the homodimer leads to inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the presence of one-electron oxidants or reductants leading to the loss of the 2Fe-2S cluster, subsequent monomerization and activation of the enzyme (By similarity).|||Widely expressed. Highly expressed in testis, and at much lower level in kidney and brain. http://togogenome.org/gene/10090:Pbx3 ^@ http://purl.uniprot.org/uniprot/O35317 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TALE/PBX homeobox family.|||Interacts with PBXIP1.|||Nucleus|||Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. http://togogenome.org/gene/10090:Vwa5b2 ^@ http://purl.uniprot.org/uniprot/Q3UR50 ^@ Sequence Caution ^@ Probable cloning artifact. http://togogenome.org/gene/10090:Gmfg ^@ http://purl.uniprot.org/uniprot/A7VJA4|||http://purl.uniprot.org/uniprot/D3YY16|||http://purl.uniprot.org/uniprot/Q9ERL7 ^@ Similarity ^@ Belongs to the actin-binding proteins ADF family. GMF subfamily. http://togogenome.org/gene/10090:Gm6902 ^@ http://purl.uniprot.org/uniprot/Q3UTA8 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Or6c70 ^@ http://purl.uniprot.org/uniprot/Q7TRH4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdh12 ^@ http://purl.uniprot.org/uniprot/O55134 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell junction|||Cell membrane|||Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions (PubMed:9651350). Acts as a regulator of cell migration, probably via increasing cell-cell adhesion (By similarity). Promotes homotypic calcium-dependent aggregation and adhesion and clusters at intercellular junctions (PubMed:9651350). Unable to bind to catenins, weakly associates with the cytoskeleton (PubMed:9651350).|||Cleaved by ADAM10 close to the transmembrane domain to release the Protocadherin-12, secreted form in the serum. Cleavage results in reduced cellular adhesion in a cell migration assay.|||Expressed in endothelial cells: localizes in vasculogenic rather than angiogenic endothelium (PubMed:9651350, PubMed:15541725). Strongly expressed in a subset of invasive cells of the placenta, named glycogen-rich trophoblasts cells (at protein level) (PubMed:15541725). glycogen-rich trophoblasts cells originate from the from the ectoplacental cone where they rapidly form tight islets (at protein level) (PubMed:16269175). In adult mice, present at high level in mesangial cells of kidney glomeruli, while expression was not detected in other types of perivascular cells (PubMed:15541725).|||Mice are viable and fertile (PubMed:15541725, PubMed:18477666). Mice however show alterations in placental development that result in embryonic growth retardation: placentas are smaller and show limited angiogenesis and mis-segregation of the labyrinthine and intermediate layers (PubMed:18477666). Mice also display modifications in the structure and function of arteries, such as rearrangement of the arterial wall elastic fibers (PubMed:22205043).|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Rai1 ^@ http://purl.uniprot.org/uniprot/Q61818 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Detected in all tissues examined with strong expression in the thymus and brain. Expressed in epithelial cells involved in organogenesis. No expression was seen in the corpus callosum of the brain.|||Haploinsufficiency cause obesity and craniofacial abnormalities. Homozygous mice die during gastrulation and organogenesis. The few surviving mice experienced postnatal growth retardation and most of them died before weaning.|||Nucleus|||Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. http://togogenome.org/gene/10090:Antxrl ^@ http://purl.uniprot.org/uniprot/A0A2U7XVH6|||http://purl.uniprot.org/uniprot/Q8BVM2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ATR family.|||Membrane http://togogenome.org/gene/10090:Nhs ^@ http://purl.uniprot.org/uniprot/B1AV60|||http://purl.uniprot.org/uniprot/B9EJX2 ^@ Similarity ^@ Belongs to the NHS family. http://togogenome.org/gene/10090:Fan1 ^@ http://purl.uniprot.org/uniprot/Q69ZT1 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAN1 family.|||Binds 2 magnesium or manganese ions per subunit.|||Interacts with FANCD2 (when monoubiquitinated). Interacts with FANCI, MLH1, MLH3 and PMS2.|||Nuclease required for the repair of DNA interstrand cross-links (ICL) recruited at sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, probably in the resolution of homologous recombination intermediates (By similarity). Not involved in DNA double-strand breaks resection. Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions (PubMed:24981866). Probably keeps excising with 3'-flap annealing until it reaches and unhooks the ICL. Acts at sites that have a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3' flap (By similarity). Also has endonuclease activity toward 5'-flaps (PubMed:24981866).|||Nucleus|||The KEN box and D-box are required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination.|||The UBZ4-type zinc finger specifically binds monoubiquitinated FANCD2.|||Ubiquitinated and degraded during mitotic exit by the APC/C-Cdh1 complex. http://togogenome.org/gene/10090:Fam205a1 ^@ http://purl.uniprot.org/uniprot/D3YZF6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Arih2 ^@ http://purl.uniprot.org/uniprot/Q9Z1K6 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (By similarity). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (By similarity).|||Belongs to the RBR family. Ariadne subfamily.|||Cytoplasm|||E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (By similarity). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (By similarity). The initial ubiquitin is then elongated (By similarity). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the ECS complex. Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination. May play a role in myelopoiesis (By similarity).|||Interacts (via RING-type zinc finger 1) with UBE2L3. Interacts (via RING-type zinc finger 2) with UBE2N. Interacts with neddylated CUL5. Interacts (via RING-type 2) with GFI1B. Interacts with GFI1; prevents its ubiquitination and proteasomal degradation. Interacts with DCUN1D1 (via UBA-like domain); promotes DCUN1D1 ubiquitination (By similarity).|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate.|||Nucleus|||The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.|||Ubiquitinated. Ubiquitination promotes proteasomal degradation. http://togogenome.org/gene/10090:Mc2r ^@ http://purl.uniprot.org/uniprot/Q544P9|||http://purl.uniprot.org/uniprot/Q64326 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with MRAP; increasing ligand-sensitivity and generation of cAMP. Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of corticotropin (ACTH) (By similarity).|||Interacts with MRAP; increasing ligand-sensitivity and generation of cAMP. Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of corticotropin (ACTH).|||Membrane|||Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP). http://togogenome.org/gene/10090:Gon7 ^@ http://purl.uniprot.org/uniprot/P0C8B4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.|||Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. GON7 plays a supporting role to the catalytic subunit OSGEP in the complex.|||Nucleus http://togogenome.org/gene/10090:Smpd5 ^@ http://purl.uniprot.org/uniprot/D6MZJ6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by anionic phospholipids, specially cardiolipin and phosphatidylserine.|||Belongs to the neutral sphingomyelinase family.|||Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide.|||Endoplasmic reticulum membrane|||Highly expressed in testis, pancreas, epididymis, and brain.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Id1 ^@ http://purl.uniprot.org/uniprot/Q6GTZ3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Nptn ^@ http://purl.uniprot.org/uniprot/P97300 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with ATP2B1; this interaction stabilizes ATP2B1 and increases ATPase activity; this interaction controls T cell calcium homeostasis following T cell activation (PubMed:28827723). Interacts with XKR8; promoting its localization at the cell membrane (By similarity).|||Isoform 1 and isoform 2 are widely expressed with variable levels in brain. Isoform 1 is expressed in cerebellum and midbrain. Isoform 1 and isoform 2 are expressed in cerebral cortex, hippocampus and striatum. Isoform 2 is more abundant in the cerebral cortex than isoform 1.|||N-glycosylated.|||Postsynaptic density|||Probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK. May also regulate neurite outgrowth by activating the FGFR1 signaling pathway. May play a role in synaptic plasticity (By similarity). Also acts as a chaperone for ATP2B1; stabilizes ATP2B1 and increases its ATPase activity. Promotes localization of XKR8 at the cell membrane (By similarity).|||Some isoforms lack the first Ig-like domain which may confer homophilic adhesion activity. However, they can bind and activate FGFR1 (By similarity). http://togogenome.org/gene/10090:Kcnk16 ^@ http://purl.uniprot.org/uniprot/G5E845 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Membrane http://togogenome.org/gene/10090:Or10a5 ^@ http://purl.uniprot.org/uniprot/Q920G5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defb21 ^@ http://purl.uniprot.org/uniprot/Q8C5Z4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Xrn2 ^@ http://purl.uniprot.org/uniprot/Q9DBR1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 5'-3' exonuclease family. XRN2/RAT1 subfamily.|||Expressed in the spleen, testis, heart, brain, lung, liver, skeletal muscle, and kidney.|||Interacts with POLR2A and SMN1/SMN2. Interacts with CDKN2AIP and NKRF. Interacts with CDKN2AIPNL; the interaction is direct. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (By similarity). Interacts with DHX34; the interaction is RNA-independent (By similarity).|||May result from the retention of an intron in the cDNA.|||Possesses 5'->3' exoribonuclease activity. May promote the termination of transcription by RNA polymerase II. During transcription termination, cleavage at the polyadenylation site liberates a 5' fragment which is subsequently processed to form the mature mRNA and a 3' fragment which remains attached to the elongating polymerase. The processive degradation of this 3' fragment by this protein may promote termination of transcription. Binds to RNA polymerase II (RNAp II) transcription termination R-loops formed by G-rich pause sites (By similarity).|||nucleolus http://togogenome.org/gene/10090:Tmem204 ^@ http://purl.uniprot.org/uniprot/Q7TQI0 ^@ Function|||Subcellular Location Annotation ^@ Can influence paracellular permeability. Appears to be involved in cell-cell interactions through adherens (By similarity).|||Cell membrane|||adherens junction http://togogenome.org/gene/10090:Cabp7 ^@ http://purl.uniprot.org/uniprot/Q91ZM8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with PI4KB. This binding competes with FREQ/NCS1 binding in a calcium-dependent manner (By similarity).|||Negatively regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity.|||The C-terminal transmembrane domain (TMD) is necessary and sufficient for membrane targeting.|||perinuclear region|||trans-Golgi network membrane http://togogenome.org/gene/10090:Haus5 ^@ http://purl.uniprot.org/uniprot/Q9D786 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS5 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||centrosome|||spindle http://togogenome.org/gene/10090:Pcf11 ^@ http://purl.uniprot.org/uniprot/G3X9Z4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Associates with the phosphorylated CTD domain of POLR2A /RNA polymerase II.|||Component of pre-mRNA cleavage complex II, which promotes transcription termination by RNA polymerase II.|||Nucleus|||Phosphorylation at Ser-120 and/or Thr-121 by WNK1 weakens its association with POLR2A/RNA polymerase II, promoting transcript release from the chromatin template and mRNA export to the cytoplasm. http://togogenome.org/gene/10090:Grin2c ^@ http://purl.uniprot.org/uniprot/A2A6S2|||http://purl.uniprot.org/uniprot/Q01098 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2C/GRIN2C subfamily.|||Cell membrane|||Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:1377365). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:1377365). Plays a role in regulating the balance between excitatory and inhibitory activity of pyramidal neurons in the prefrontal cortex (PubMed:27922130). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (PubMed:8987814).|||Detected in cerebellum (at protein level) (PubMed:8987814). Detected in the granule cell layer of the cerebellum (PubMed:1377365).|||Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1377365). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By similarity). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Interacts with PDZ domains of PATJ and DLG4 (By similarity). Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (By similarity).|||Membrane|||Mutant mice appear grossly normal (PubMed:8987814). Mossy fiber granule cells from mutant mice present a decrease of the slow component of the excitatory postsynaptic current (PubMed:8987814). Pyramidal neurons in the prefrontal cortex display a reduced dendritic spine density (PubMed:27922130). Besides, the prefrontal cortex has an altered pattern of excitatory and inhibitory synapses (PubMed:27922130). Pyramidal neurons in the prefrontal cortex display a reduced frequency of miniature excitatory postsynaptic currents (mEPSC), together with an increased frequency of miniature inhibitory postsynaptic currents (mIPSC), indicative of a shift in the balance between excitatory and inhibitory membrane currents (PubMed:27922130). The slow component of the excitatory postsynaptic current is nearly abolished in mossy fiber cells from mice lacking both Grin2a and Grin2c (PubMed:8987814). Mice lacking both Grin2a and Grin2c display subtle motor deficits; they have no visible phenotype when performing simple tasks, but have decreased ability to walk across a narrow wooden bar, and are unable to stay on a rapidly rotating rod (PubMed:8987814).|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.|||Synaptic cell membrane http://togogenome.org/gene/10090:Mmp25 ^@ http://purl.uniprot.org/uniprot/Q3U435 ^@ Caution|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||In contrast to the human ortholog it does not have a signal sequence as it has an additional 53 residue sequence at the N-terminus. At the position of the human initiation methionine there is a leucine (Leu-54).|||May activate progelatinase A.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase. http://togogenome.org/gene/10090:Rai2 ^@ http://purl.uniprot.org/uniprot/Q9QVY8 ^@ Induction ^@ By retinoic acid. http://togogenome.org/gene/10090:Mgat4a ^@ http://purl.uniprot.org/uniprot/Q812G0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 54 family.|||Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary N-linked sugar chains (PubMed:16377570). Involved in glucose transport by mediating SLC2A2/GLUT2 glycosylation, thereby controlling cell-surface expression of SLC2A2 in pancreatic beta cells (PubMed:16377570).|||Golgi apparatus membrane|||Inhibited by UDP.|||Mice display impaired beta cell glucose transport and insulin secretion causing type 2 diabete. This is due to defects in SLC2A2/Glut-2 glycosylation, provoking SLC2A2/Glut-2 endocytosis with redistribution into endosomes and lysosomes.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Tcp10a ^@ http://purl.uniprot.org/uniprot/Q80W76 ^@ Similarity ^@ Belongs to the TCP10 family. http://togogenome.org/gene/10090:Zdhhc11 ^@ http://purl.uniprot.org/uniprot/Q14AK4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DHHC palmitoyltransferase family.|||Endoplasmic reticulum-localized palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes (PubMed:23687301). Has a palmitoyltransferase activity toward NCDN and regulates NCDN association with endosome membranes through this palmitoylation (PubMed:23687301). May play a role in cell proliferation (By similarity).|||Endosome membrane|||Has also a palmitoyltransferase activity-independent function in DNA virus-triggered and CGAS-mediated innate immune response (PubMed:29429998). Functions as an adapter that recruits IRF3 to STING1 to promote the activation of that key transcriptional regulator of type I interferon (IFN)-dependent immune response (PubMed:29429998).|||Homozygous knockout mice are viable and do not show overt phenotype (PubMed:29429998). Composition and number of major immune cells is normal but mice are more susceptible to DNA-virus infection and death than their wild-type counterpart (PubMed:29429998).|||Interacts with IRF3 and STING1; in presence of DNA viruses recruits IRF3 to STING1 promoting IRF3 phosphorylation and activation.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Rab29 ^@ http://purl.uniprot.org/uniprot/E9QLQ7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Membrane|||The small GTPases Rab are key regulators in vesicle trafficking. http://togogenome.org/gene/10090:Casr ^@ http://purl.uniprot.org/uniprot/Q9QY96 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Epidermis, kidney and cartilage.|||G-protein-coupled receptor that senses changes in the extracellular concentration of calcium ions and plays a key role in maintaining calcium homeostasis (By similarity). Senses fluctuations in the circulating calcium concentration and modulates the production of parathyroid hormone (PTH) in parathyroid glands (PubMed:7493018). The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system (By similarity). The G-protein-coupled receptor activity is activated by a co-agonist mechanism: aromatic amino acids, such as Trp or Phe, act concertedly with divalent cations, such as calcium or magnesium, to achieve full receptor activation (By similarity).|||Heterozygous mice show benign and modest elevations of serum calcium, magnesium and parathyroid hormone levels as well as hypocalciuria. Homozygous mice show neonatal severe hyperparathyroidism, had markedly elevated serum calcium and parathyroid hormone levels, parathyroid hyperplasia, bone abnormalities, retarded growth and premature death.|||Homodimer; disulfide-linked. Interacts with VCP and RNF19A (By similarity). Interacts with ARRB1 (By similarity).|||In resting state, adopts an open conformation, anion-binding promoting the inactive configuration. Upon aromatic amino acid-binding, the groove in the extracellular venus flytrap module is closed, thereby inducing the formation of a novel homodimer interface between subunits. Calcium ions stabilize the active state by enhancing homodimer interactions between membrane-proximal domains to fully activate the receptor.|||N-glycosylated.|||The extracellular regions of the homodimer interact in a side-by-side fashion while facing opposite directions. Each extracellular region consists of three domains, LB1 (ligand-binding 1), LB2 and CR (cysteine-rich). The two lobe-shaped domains LB1 and LB2 form a venus flytrap module. In the inactive configuration, the venus flytrap modules of both protomers are in the open conformation associated with the resting state (open-open) and the interdomain cleft is empty. In addition, each protomer contains three anions, which reinforce the inactive conformation, and one calcium ion. In the active configuration, both protomers of extracellular regions have the closed conformation associated with agonist-binding (closed-closed). The ligand-binding cleft of each protomer is solely occupied by an aromatic amino-acid. Calcium is bound at four novel sites, including one at the homodimer interface. Agonist-binding induces large conformational changes within the extracellular region homodimer: first, the venus flytrap module of each protomer undergoes domain closure. Second, the LB2 regions of the two protomers approach each other, resulting in an expansion of the homodimer interactions involving LB2 domains. Third, the CR regions of the two subunits interact to form a large homodimer interface that is unique to the active state. The CR regions are brought into close contact by the motion involving LB2 since the two domains are rigidly associated within each subunit.|||Ubiquitinated by RNF19A; which induces proteasomal degradation. http://togogenome.org/gene/10090:Or2ag1b ^@ http://purl.uniprot.org/uniprot/K7N641 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nxt1 ^@ http://purl.uniprot.org/uniprot/Q9QZV9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Heterodimer with NXF1. Forms a complex with RANGAP1, RANBP2/NUP358 and NXF1. Interacts (via NTF2 domain) with NXF1. Stabilizes the NTF2 domain of NXF1 by heterodimerization. The formation of NXF1-NXT1 heterodimers is required for the NXF1-mediated nuclear mRNA export. Preferentially binds Ran-GTP. Associates with NXF2, NXF3 and NXF5. Does not bind nucleoporins (NPC) directly, its association to NPC is mediated by NXF1.|||Nucleus|||Nucleus speckle|||Stimulator of protein export for NES-containing proteins. Also plays a role in the nuclear export of U1 snRNA, tRNA, and mRNA. The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 (By similarity). http://togogenome.org/gene/10090:Hip1 ^@ http://purl.uniprot.org/uniprot/Q8VD75 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLA2 family.|||Binds F-actin via the talin-like I/LWEQ domain.|||Cytoplasm|||Endomembrane system|||Homodimer. Binds actin. Binds HTT (via N-terminus). This interaction is restricted to the brain. Binds to IFT57. In normal conditions, it poorly interacts with IFT57, HIP1 being strongly associated with HTT. However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57. Interacts with CLTB (via N-terminus). Interacts (via coiled coil domain) with AR. Interacts with AP2A1, AP2A2, CLTC and HIP1R (By similarity). Interacts with GRIA1, GRIN2A and GRIN2B.|||Mice develop a neurological phenotype by 3 months of age, characterized by wasting, tremor and a gait ataxia secondary to a rigid thoracolumbar kyphosis (PubMed:12839988, PubMed:14998932). Recovery of synaptic transmission following synaptic depression induced by prolonged nerve stimulation is reduced (PubMed:17928447). Paired-pulse facilitation, a form of neuronal plasticity in which delivery of two stimuli within a second of each other produces an increase in the size of the second synaptic response, is enhanced (PubMed:17928447). They also display micro-ophthalmia with nuclear cataracts (PubMed:14998932). Mutant male mice are mostly infertile and exhibit testicular degeneration with increased apoptosis of postmeiotic spermatids (PubMed:11604514, PubMed:16967501). Hip1 and Hip1r double-knockout mice are dwarfed, afflicted with severe vertebral defects and die in early adulthood (PubMed:17452370).|||Most abundantly expressed in brain. In brain, expressed in cortical tissue, hippocampus, the molecular layer of the cerebellum and olfactory bulb. Also expressed in spinal cord and bone marrow (at protein level). Expressed in reproductive tissues.|||Nucleus|||Plays a role in clathrin-mediated endocytosis and trafficking (PubMed:11577110). Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner (PubMed:12839988, PubMed:17329427). Regulates presynaptic nerve terminal activity (PubMed:17928447). Enhances androgen receptor (AR)-mediated transcription (By similarity). May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway (By similarity). Binds 3-phosphoinositides (via ENTH domain) (By similarity). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis (By similarity). May play a functional role in the cell filament networks (By similarity). May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors (PubMed:11604514, PubMed:14998932, PubMed:16967501, PubMed:17928447).|||The pseudo DED region (pDED) mediates the interaction with IFT57.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Noto ^@ http://purl.uniprot.org/uniprot/Q5TIS6 ^@ Developmental Stage|||Disease Annotation|||Function|||Subcellular Location Annotation ^@ Defects in Noto are the cause of the truncate (tc) phenotype. Truncate (tc) is a recessive mutation that affects the development of the caudal notochord. Mice homozygous for tc are viable but viability is reduced, which is attributed at least in part to spinal injury in the sacral and lower lumbar region.|||First detected at 7.5 dpc in the node at the distal tip of the egg cylinder and is largely confined to the ventral node. Between 8 dpc and 9 dpc, highly expressed in the node and newly formed notochord. At 12.5 dpc, expression is confined to the notochordal plate and caudal portion of the notochord.|||Nucleus|||Transcription factor that controls node morphogenesis (PubMed:15231714, PubMed:17884984, PubMed:18061569, PubMed:22357932). Acts downstream of both FOXA2 and Brachyury (T) during notochord development (PubMed:15231714). Is essential for cilia formation in the posterior notochord (PNC) and for left-right patterning; acts upstream of FOXJ1 and RFX3 in this process and is required for the expression of various components important for axonemal assembly and function (PubMed:17884984). Plays a role in regulating axial versus paraxial cell fate (PubMed:18061569). Activates the transcription of ciliary proteins C11orf97 homolog, FAM183B and SPACA9 in the embryonic ventral node (PubMed:27914912). http://togogenome.org/gene/10090:Josd2 ^@ http://purl.uniprot.org/uniprot/Q9CR30 ^@ Function|||Subcellular Location Annotation ^@ Cleaves 'Lys-63'-linked poly-ubiquitin chains, and with lesser efficiency 'Lys-48'-linked poly-ubiquitin chains (in vitro). May act as a deubiquitinating enzyme (By similarity).|||cytosol http://togogenome.org/gene/10090:Rab43 ^@ http://purl.uniprot.org/uniprot/Q0PD10|||http://purl.uniprot.org/uniprot/Q8CG50 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Golgi apparatus|||Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-80 disrupts these interactions.|||Membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The low intrinsic GTPase activity of RAB43 is activated by USP6NL. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for the structural integrity of the Golgi complex. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and Mycobacterium.|||phagosome|||phagosome membrane|||trans-Golgi network|||trans-Golgi network membrane http://togogenome.org/gene/10090:Cmtm2a ^@ http://purl.uniprot.org/uniprot/Q9DAR1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chemokine-like factor family.|||Membrane http://togogenome.org/gene/10090:Tm2d3 ^@ http://purl.uniprot.org/uniprot/Q8BJ83 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TM2 family.|||Membrane http://togogenome.org/gene/10090:Garem2 ^@ http://purl.uniprot.org/uniprot/Q6PAJ3 ^@ Function|||Similarity ^@ Belongs to the GAREM family.|||Probable adapter protein that provides a critical link between cell surface epidermal growth factor receptor and the MAPK/ERK signaling pathway. http://togogenome.org/gene/10090:Or5ac21 ^@ http://purl.uniprot.org/uniprot/A0A1L1SSG9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vipr2 ^@ http://purl.uniprot.org/uniprot/P41588|||http://purl.uniprot.org/uniprot/Q546Q8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Expressed at high levels in the MIN6 cells, at moderate levels in pancreatic islets, insulin-secreting cells, lung, brain, stomach, and colon, and at low levels in the heart.|||Membrane|||This is a receptor for VIP as well as PACAP-38 and -27, the activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Can be coupled to phospholipase C. http://togogenome.org/gene/10090:Snta1 ^@ http://purl.uniprot.org/uniprot/A2AKD7|||http://purl.uniprot.org/uniprot/Q3UVD6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the syntrophin family.|||Cell junction|||cytoskeleton http://togogenome.org/gene/10090:Flad1 ^@ http://purl.uniprot.org/uniprot/Q8R123 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme.|||Cytoplasm|||In the C-terminal section; belongs to the PAPS reductase family. FAD1 subfamily.|||In the N-terminal section; belongs to the MoaB/Mog family.|||The molybdenum cofactor biosynthesis protein-like region may not be functional. http://togogenome.org/gene/10090:Bcr ^@ http://purl.uniprot.org/uniprot/A2RRK7|||http://purl.uniprot.org/uniprot/Q6PAJ1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated by FES/FPS on tyrosine residues, leading to down-regulation of the BCR kinase activity. Phosphorylation at Tyr-178 by HCK is important for interaction with GRB2.|||Expressed in brain (PubMed:25331951). In hippocampal subregions, most abundant in the CA1 region and expressed at successively lower levels in the dentate gyrus and the CA3 region (PubMed:20962234).|||Homotetramer. Interacts with PDZK1. Interacts with HCK, FES/FPS, ABL1, PIK3R1 and GRB2 (By similarity). May interact with CCPG1 (PubMed:17000758). Interacts with SH2D5 (PubMed:25331951). Interacts with DLG4 (By similarity).|||Mutant mice show impaired spatial and object recognition memory with reduced maintenance of long-term potentiation (LTP) in Schaffer collateral-CA1 pyramidal neuron synapses.|||Postsynaptic density|||Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The amino terminus contains an intrinsic kinase activity (By similarity). Functions as an important negative regulator of neuronal RAC1 activity (PubMed:20962234). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (By similarity).|||Synapse|||The DH domain is involved in interaction with CCPG1.|||The amino terminus contains an intrinsic kinase activity. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.|||The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene.|||axon|||dendritic spine http://togogenome.org/gene/10090:Col8a1 ^@ http://purl.uniprot.org/uniprot/Q00780 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ COL8A1(-)/COL8A2(-) mice exhibit decreased proliferation of measngial cells, reduced phosphorylation of ERK1/2 and increased p27(KIP1) expression. Diabetic COL8A1(-)/COL8A2(-) mice reveal reduced mesangial expansion and cellularity and extracellular matrix expansion.|||High levels in calvarium, eye and skin of newborn mice; also in various epithelial, endothelial and mesenchymal cells.|||Homotrimers, or heterotrimers in association with alpha 2(VIII) type collagens. Four homotrimers can form a tetrahedron stabilized by central interacting C-terminal NC1 trimers (By similarity).|||Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also a component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Proteolytically cleaved by neutrophil elastase, in vitro. Proteolytic processing produces the C-terminal NC1 domain fragment, vastatin (By similarity).|||Up-regulated in astrocytes during the repair process and in mesangial cells in diabetic animals.|||Vastatin, the C-terminal fragment comprising the NC1 domain, inhibits aortic endothelial cell proliferation and causes cell apoptosis.|||basement membrane http://togogenome.org/gene/10090:Or5g9 ^@ http://purl.uniprot.org/uniprot/A2ALD4|||http://purl.uniprot.org/uniprot/Q8VFK1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Cacna1d ^@ http://purl.uniprot.org/uniprot/A0A286YD72|||http://purl.uniprot.org/uniprot/A0A589Q4M7|||http://purl.uniprot.org/uniprot/Q99246 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1D subfamily.|||Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.|||Expressed in the inner hair cells (IHC) of the cochlea.|||Isoform 2 and isoform 3 are expressed in heart at 12.5 dpc (at protein level). Expressed in the heart at 9.5, 12.5 and 15.5 dpc. Isoform 2 and isoform 3 are expressed in heart at 9.5 and 12.5 dpc.|||Membrane|||Up-regulated in CACNA1C knockout mice.|||Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interacts (via IQ domain) with CABP1 and CABP4 in a calcium independent manner. Interacts with RIMBP2 (By similarity).|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death.|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.|||deafness, bradycardia and diabetic traits. http://togogenome.org/gene/10090:1110004F10Rik ^@ http://purl.uniprot.org/uniprot/Q9R0P4 ^@ Similarity ^@ Belongs to the SMAP family. http://togogenome.org/gene/10090:F12 ^@ http://purl.uniprot.org/uniprot/Q80YC5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S1 family.|||Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa (By similarity).|||Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation.|||O- and N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Lars2 ^@ http://purl.uniprot.org/uniprot/Q8VDC0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Mitochondrion matrix http://togogenome.org/gene/10090:Cd200r3 ^@ http://purl.uniprot.org/uniprot/Q5UKY4 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:15187158 isoform 4 is a receptor for the CD200 cell surface glycoprotein. According to PubMed:16081818 isoform 4 is not a receptor for the CD200/OX2 cell surface glycoprotein. Isoform 1, isoform 2 and isoform 3 are involved in the recruitment or surface expression of the TYROBP receptor. Isoform 6, isoform 7 and isoform 8 are not involved in the recruitment or surface expression of the TYROBP receptor.|||According to some authors, isoform 3 (truncated at the N-terminus) is not a receptor for the CD200/OX2 cell surface glycoprotein.|||Belongs to the CD200R family.|||Expressed in uterus and bone marrow-derived mast cells (at protein level). Expressed in uterus, spleen, bone marrow-derived dendritic, basophil and mast cells. Expressed in the lung of N.brasiliensis-infected mice. Weakly expressed in brain, testis, lung and thymus.|||Expressed in uterus at 12.5 dpc (at protein level).|||Isoform 3 interacts with TYROBP. Isoform 8 does not interact with TYROBP.|||Membrane http://togogenome.org/gene/10090:Snapc3 ^@ http://purl.uniprot.org/uniprot/Q9D2C9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNAPC3/SRD2 family.|||Nucleus|||Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC3 interacts with SNAPC1 (By similarity).|||Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box (By similarity). http://togogenome.org/gene/10090:Cacna1f ^@ http://purl.uniprot.org/uniprot/Q7TNI3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.|||Membrane|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. http://togogenome.org/gene/10090:Extl3 ^@ http://purl.uniprot.org/uniprot/Q6P1H4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 47 family.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Skic8 ^@ http://purl.uniprot.org/uniprot/Q9ERF3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKI8 family.|||Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency (PubMed:19345177). PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1 (By similarity). PAF1C is required for transcription of Hox and Wnt target genes (By similarity). PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL (By similarity). PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3) (By similarity). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription (By similarity). PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors (By similarity). In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription (By similarity). Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3), dimethylation on histone H3 'Lys-79' (H3K4me3) (By similarity). Required for Hox gene transcription (By similarity). Also acts as a component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (By similarity). The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation (By similarity). SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling (By similarity).|||Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. The PAF1 complex interacts with PHF5A (PubMed:27749823). Within the PAF1 complex interacts directly with PHF5A (PubMed:27749823). Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8 (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Orc6 ^@ http://purl.uniprot.org/uniprot/Q66JV6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ORC6 family.|||Nucleus http://togogenome.org/gene/10090:Tnfrsf26 ^@ http://purl.uniprot.org/uniprot/P83626|||http://purl.uniprot.org/uniprot/Q3U3N2 ^@ Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in thymus and spleen. Detectable levels in lung.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Gimd1 ^@ http://purl.uniprot.org/uniprot/E9PW74 ^@ Similarity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily. http://togogenome.org/gene/10090:Gigyf2 ^@ http://purl.uniprot.org/uniprot/Q6Y7W8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GIGYF family.|||Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:26763119). Interacts (via the 4EHP-binding motif) with EIF4E2; the interaction is direct (By similarity). Interacts with ZFP36/TTP (via P-P-P-P-G repeats); the interaction is direct (PubMed:26763119). Interacts with GRB10 (PubMed:12771153). Interacts (via DDX6 motif) with DDX6 (via RecA-like domain 2) (By similarity).|||Expressed in heart, liver, kidney and brain as well as in testis (PubMed:12771153).|||Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:26763119). In the 4EHP-GYF2 complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (PubMed:26763119). Also recruits and bridges the association of the 4EHP complex with the decapping effector protein DDX6, which is required for the ZFP36/TTP-mediated down-regulation of AU-rich mRNA (By similarity). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153). In association with EIF4E2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide. GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist (By similarity).|||Mice undergo normal embryonic development, but fail to feed and die within the first 2 postnatal days. Heterozygous mice survive to adulthood with no evident metabolic or growth defects. At 12-15 months of age, heterozygous mice show motor dysfunction associated with histopathologic evidence of neurodegeneration and rare intracytoplasmic Lewy body-like inclusions in spinal anterior horn motor neurons.|||Widely expressed in embryonic tissues, including strong expression in the central nervous system. http://togogenome.org/gene/10090:Gdf2 ^@ http://purl.uniprot.org/uniprot/Q9WV56 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A reversible disulfide bond can be formed between the two subunits in the homodimer; this has no effect on GDF2 activity.|||Belongs to the TGF-beta family.|||Can promote osteogenic differentiation in vitro (PubMed:25751889). This is probably not physiologically relevant.|||Homodimer; disulfide-linked. Detected in extracellular fluid as mature homodimer, and in complex with its propeptide (By similarity). Interacts with ACVRL1, BMPR2 and ACVR2B with high affinity (in vitro) (PubMed:25751889). Identified in a complex with ACVRL1 and ACVR2B (By similarity). Has ten times lower affinity for ACVR2A (in vitro) (PubMed:25751889). Interacts with ENG, forming a heterotetramer with a 2:2 stoichiometry. Can form a heteromeric complex with ENG and ACVRL1 (By similarity). Interacts with type I receptor ACVR1 (By similarity).|||Potent circulating inhibitor of angiogenesis (By similarity). Signals through the type I activin receptor ACVRL1 but not other Alks (PubMed:25751889). Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG (PubMed:23300529).|||Secreted http://togogenome.org/gene/10090:Moap1 ^@ http://purl.uniprot.org/uniprot/Q9ERH6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PNMA family.|||Extracellular vesicle membrane|||Homodimer. Under normal circumstances, held in an inactive conformation by an intramolecular interaction. Interacts with BAX. Binding to RASSF1 isoform A (RASSF1A) relieves this inhibitory interaction and allows further binding to BAX. Binds also to BCL2 and BCLX. Recruited to the TNFRSF1A and TNFRSF10A complexes in response to their respective cognate ligand, after internalization. Interacts with TRIM39 (By similarity). Interacts with RASSF6 (PubMed:17404571). Interacts with ATG8 proteins MAP1LC3A, MAP1LC3B and MAP1LC3C (By similarity). Does not interact with ATG8 proteins GABARAPL1, GABARAPL2 and GABARAP (By similarity). Interacts with SQSTM1; promoting dissociation of SQSTM1 inclusion bodies that sequester KEAP1 (By similarity).|||Mitochondrion outer membrane|||Retrotransposon-derived protein that forms virion-like capsids (PubMed:34413232). Acts as an effector of BAX during apoptosis: enriched at outer mitochondria membrane and associates with BAX upon induction of apoptosis, facilitating BAX-dependent mitochondrial outer membrane permeabilization and apoptosis (By similarity). Required for death receptor-dependent apoptosis (By similarity). When associated with RASSF1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation (By similarity). Also promotes autophagy: promotes phagophore closure via association with ATG8 proteins (PubMed:33783314). Acts as an inhibitor of the NFE2L2/NRF2 pathway via interaction with SQSTM1: interaction promotes dissociation of SQSTM1 inclusion bodies that sequester KEAP1, relieving inactivation of the BCR(KEAP1) complex (By similarity).|||The BH3-like domain is required for association with BAX and for mediating apoptosis. The three BH domains (BH1, BH2, and BH3) of BAX are all required for mediating protein-protein interaction.|||The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins MAP1LC3A, MAP1LC3B and MAP1LC3C.|||The protein is evolutionarily related to retrotransposon Gag proteins: it contains the capsid (CA)subdomain of gag.|||Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1, this modification is inhibited by TRIM39.|||Widely expressed, including in the brain. High expression levels in testis.|||cytosol http://togogenome.org/gene/10090:Eya4 ^@ http://purl.uniprot.org/uniprot/A0A1W2P721|||http://purl.uniprot.org/uniprot/Q8BY78|||http://purl.uniprot.org/uniprot/Q9Z191 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HAD-like hydrolase superfamily. EYA family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||In the embryo, expressed mainly in the craniofacial mesenchyme, dermamyotome and limb.|||Interacts with SIX3; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes.|||Nucleus|||Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. May be involved in development of the eye (By similarity). http://togogenome.org/gene/10090:H4c18 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Poc1b ^@ http://purl.uniprot.org/uniprot/Q8BHD1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat POC1 family.|||Expressed in the retina.|||Interacts with POC1A. Interacts with FAM161A. Interacts with CEP44; the interaction is direct and recruits POC1B to centriolar microtubules.|||Phosphorylated in mitotic cells that may be mediated by CDK1.|||Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1A to ensure centriole integrity and proper mitotic spindle formation. Required for primary cilia formation, ciliary length and also cell proliferation. Required for retinal integrity.|||centriole|||cilium basal body|||spindle pole http://togogenome.org/gene/10090:Crybg1 ^@ http://purl.uniprot.org/uniprot/E9PVP1 ^@ Similarity ^@ Belongs to the beta/gamma-crystallin family. http://togogenome.org/gene/10090:Oscar ^@ http://purl.uniprot.org/uniprot/Q8VBT3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the leukocyte receptor complex/polymeric immunoglobulin receptor (PIR/LRC) family.|||Cell membrane|||Regulator of osteoclastogenesis which plays an important bone-specific function in osteoclast differentiation.|||Specifically expressed in preosteoclasts or mature osteoclasts. http://togogenome.org/gene/10090:Serpini2 ^@ http://purl.uniprot.org/uniprot/Q4G0D3|||http://purl.uniprot.org/uniprot/Q9JK88 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Expressed in pancreas.|||Secreted http://togogenome.org/gene/10090:Vti1b ^@ http://purl.uniprot.org/uniprot/Q91XH6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the VTI1 family.|||Membrane http://togogenome.org/gene/10090:Zscan26 ^@ http://purl.uniprot.org/uniprot/Q5RJ54 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Agmo ^@ http://purl.uniprot.org/uniprot/Q8BS35 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sterol desaturase family. TMEM195 subfamily.|||Endoplasmic reticulum membrane|||Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids. Ether lipids are essential components of brain membranes (By similarity).|||Highly expressed in lever and small intestine.|||Intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:C1qtnf9 ^@ http://purl.uniprot.org/uniprot/Q4ZJN1 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed predominantly in adipose tissue. Females express higher levels than males.|||Multimers (predominantly trimers). Interacts with ADIPOQ via the C1q domain to form a heterotrimeric complex.|||Overexpression of CTRP9 in obese (ob/ob) mice significantly lowered serum glucose levels.|||Probable adipokine. Activates AMPK, AKT, and p44/42 MAPK signaling pathways.|||Secreted|||The isomeric forms of the hydroxylated amino acids could not be determined in the mass-spectrometric methods reported in PubMed:18787108 but are assumed on the basis of their occurrence in collagen-like domains. http://togogenome.org/gene/10090:Tfec ^@ http://purl.uniprot.org/uniprot/Q9WTW4 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MiT/TFE family.|||Contains an activation domain in the C-terminal region.|||Expressed in osteoclast-like cells (at protein level). Expressed in cells of the mononuclear phagocyte lineage. Expressed in macrophages and in osteoclast-like cells.|||Expressed in the early developing retinal pigmented epithelium and in the peripheral retina.|||Homodimer. Forms heterodimers with MITF. Interacts with MITF. Forms heterodimers with TFE3 (By similarity).|||Nucleus|||Transcriptional regulator that acts as a repressor or an activator. Acts as a transcriptional transactivator on the proximal promoter region of the tartrate-resistant acid phosphatase (TRAP) E-box containing promoter. Collaborates with MITF in target gene activation. Acts as a transcriptional repressor on minimal promoter containing element F (that includes an E-box sequence) (By similarity). Binds to element F in an E-box sequence-specific manner (By similarity). Acts as a transcriptional repressor on minimal promoter containing mu E3 enhancer sequence (By similarity). Binds to mu E3 DNA sequence of the immunoglobulin heavy-chain gene enhancer (By similarity). Binds DNA in a homo- or heterodimeric form.|||Up-regulated in bone marrow-derived macrophages by Th2 cytokines, IL-4, IL-13 and LPS. http://togogenome.org/gene/10090:Myh9 ^@ http://purl.uniprot.org/uniprot/Q8VDD5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping (PubMed:19401332). Required for cortical actin clearance prior to oocyte exocytosis (PubMed:31118423). Promotes cell motility in conjunction with S100A4 (By similarity). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (By similarity).|||Cortical granule|||ISGylated.|||In neonatal mouse cochlea, weak levels of expression in both hair cells and supporting cells (at protein level). In the cochlea of six day old mice, expression is restricted to hair cell sterocilia (at protein level).|||Myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2). Interacts with RASIP1 (PubMed:21396893). Interacts with DDR1 (PubMed:19401332). Interacts with PDLIM2 (By similarity). Interacts with SVIL (By similarity). Interacts with HTRA3 (By similarity). Interacts with Myo7a (PubMed:27331610). Interacts with CFAP95 (By similarity). Interacts with LIMCH1; independently of the integration of MYH9 into the myosin complex (By similarity). Interacts with RAB3A (By similarity). Interacts with ZBED4 (By similarity). Interacts with S100A4; this interaction increases cell motility.|||Reduced litter size and increased polyspermy in the perivitelline space following fertilization.|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||Ubiquitination.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Adamtsl2 ^@ http://purl.uniprot.org/uniprot/Q7TSK7 ^@ Caution|||PTM|||Subcellular Location Annotation|||Subunit ^@ Although strongly similar to members of the ADAMTS family it lacks the metalloprotease and disintegrin-like domains which are typical of that family.|||Glycosylated (By similarity). Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Interacts with LTBP1.|||Secreted http://togogenome.org/gene/10090:Bgn ^@ http://purl.uniprot.org/uniprot/P28653|||http://purl.uniprot.org/uniprot/Q3TNY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.|||Found in several connective tissues, especially in articular cartilages.|||May be involved in collagen fiber assembly.|||The two attached glycosaminoglycan chains can be either chondroitin sulfate or dermatan sulfate.|||extracellular matrix http://togogenome.org/gene/10090:Dio2 ^@ http://purl.uniprot.org/uniprot/Q9QXV5|||http://purl.uniprot.org/uniprot/Q9Z1Y9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the iodothyronine deiodinase family.|||Expressed in mammary gland and in brain.|||Interacts with USP20 and USP33. Interacts with MARCHF6 (By similarity).|||Membrane|||Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.|||Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine).|||Ubiquitinated by MARCHF6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33 (By similarity). http://togogenome.org/gene/10090:Mast2 ^@ http://purl.uniprot.org/uniprot/B1AST7|||http://purl.uniprot.org/uniprot/B1AST8|||http://purl.uniprot.org/uniprot/Q60592 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins. Functions in a multi-protein complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cell junction|||Detected in round spermatids and residual bodies but not epididymal spermatozoa (at protein level). Expressed in adult but not fetal testis with levels increasing in parallel with testicular development. Also expressed at high levels in heart, lower levels in all other tissues tested.|||Interacts with CDHR2.|||Membrane|||Phosphorylated and ubiquitinated. N-terminal ubiquitination leads to degradation of MAST2 by proteasome-mediated proteolysis. N-terminal phosphorylation appears to be a prerequisite for ubiquitination.|||cytoskeleton http://togogenome.org/gene/10090:Atf7ip ^@ http://purl.uniprot.org/uniprot/Q7TT18 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MCAF family.|||Interacts with MBD1; the interaction is enhanced when MBD1 is sumoylated (By similarity). Interacts with SETDB1; the interaction protects SETDB1 from proteasomal degradation and is required to stimulate histone methyltransferase activity and facilitate the conversion of dimethylated to trimethylated H3 'Lys-9' (PubMed:14536086). Interacts with SUMO ubiquitin-like proteins (SUMO1, SUNO2 and SUMO3), with a preference for SUMO2 and SUMO3. Interacts with SP1, ATF7 and ZHX1. Interacts with the general transcription machinery, including ERCC2, ERCC3, GTF2E1, GTF2E2 and POLR2A (By similarity).|||Nucleus|||Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context (PubMed:10777215). Required for HUSH-mediated heterochromatin formation and gene silencing (By similarity). Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing SETDB1. Stabilizes SETDB1, is required to stimulate histone methyltransferase activity of SETDB1 and facilitates the conversion of dimethylated to trimethylated H3 'Lys-9' (H3K9me3). The complex formed with MBD1 and SETDB1 represses transcription and couples DNA methylation and histone H3 'Lys-9' trimethylation (H3K9me3) (PubMed:14536086). Facilitates telomerase TERT and TERC gene expression by SP1 in cancer cells (By similarity).|||Ubiquitously expressed at all stages studied. http://togogenome.org/gene/10090:Odf3l1 ^@ http://purl.uniprot.org/uniprot/Q810P2 ^@ Similarity ^@ Belongs to the CIMAP family. http://togogenome.org/gene/10090:Chtf8 ^@ http://purl.uniprot.org/uniprot/P0CG14|||http://purl.uniprot.org/uniprot/P0CG15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTF8 family.|||Belongs to the DERPC family.|||Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DSCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated the presence of primed DNA, replication protein A (RPA) and proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. It also interacts with and stimulates POLH, which is suggestive of a protein network that coordinates DNA repair, recombination and chromosome cohesion reactions with replication fork progression (By similarity).|||Component of the CTF18-RFC complex, which consists of CTF18, CTF8, DSCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex does not interact with the Rad9/Rad1/Hus1 complex. The CTF18-RFC complex interacts with POLH. CTF18/CTF8/DSCC1 associate with PCNA. CTF8 exists as a dimer with DSCC1 (By similarity).|||Nucleus|||Potential tumor suppressor. http://togogenome.org/gene/10090:Llph ^@ http://purl.uniprot.org/uniprot/Q9D945 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the learning-associated protein family.|||Chromosome|||In hippocampal neurons, regulates dendritic and spine growth and synaptic transmission.|||In the hippocampal neurons, down-regulated by sustained activity induced by increased extracellular potassium concentration for a prolonged time (2 - 5 hours) (at protein level).|||Interacts with CTCF, MYO1C and with the transcriptional machinery, including RNA polymerase II and TBP.|||Strongly expressed in the brain in early developmental stages. Expression gradually decreases during development, from very high levels at 13 dpc down to hardly detectable in the adult at day 20 postnatal and later on (at protein level).|||Widely expressed, with high levels in testis and spleen and low levels in heart. In the brain, expressed in the cortex and hippocampus, and at very low levels in the cerebellum.|||nucleolus http://togogenome.org/gene/10090:Slc5a5 ^@ http://purl.uniprot.org/uniprot/G3X8P5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r247 ^@ http://purl.uniprot.org/uniprot/D3YTW8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adam34l ^@ http://purl.uniprot.org/uniprot/Q7M766 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Gnb2 ^@ http://purl.uniprot.org/uniprot/P62880|||http://purl.uniprot.org/uniprot/Q3U9V4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat G protein beta family.|||Cell membrane|||Expressed in meiotically incompetent oocytes. Expression increases in fully grown meiotically competent oocytes. Expression then decreases during metaphase-II arrested eggs, one-cell embryo, two-cell embryo and eight-cell embryo stages, and increases again during blastocyst stage.|||G proteins are composed of 3 units, alpha, beta and gamma. In this context, interacts with GNAI2 and GNG2 (By similarity). Interacts with ARHGEF18 and RASD2. Interacts with ATXN10. Interacts with SCN8A.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||perinuclear region http://togogenome.org/gene/10090:Cab39 ^@ http://purl.uniprot.org/uniprot/Q06138 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mo25 family.|||Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1 (By similarity).|||Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.|||Cytoplasm|||Transcribed during early mouse development. Detected at all developmental stages from the egg through the blastocyst, most abundant at the 2-cell stage. http://togogenome.org/gene/10090:Emc9 ^@ http://purl.uniprot.org/uniprot/Q793L1|||http://purl.uniprot.org/uniprot/Q9DB76 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC8/EMC9 family.|||Component of the ER membrane protein complex (EMC). EMC8 and EMC9 are mutually exclusive subunits of the EMC complex.|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Ypel1 ^@ http://purl.uniprot.org/uniprot/A0A338P6Z8|||http://purl.uniprot.org/uniprot/Q65Z96|||http://purl.uniprot.org/uniprot/Q9ESC7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ At 9.5 dpc, expressed throughout the ventral mesoderm of the trunk and head. At 10.5 dpc, maintained in the ventral aspect of the axial tissues; detected in the branchial clefts, branchial arches, in the heart and in the cranial mesenchyme underlying the mid-brain. No expression in the dorsal part of the embryo, in the somatopleure nor in the splanchnopleure. At 11.0 dpc, expressed in the branchial arches in the mesenchyme underlying the ectoderm, but not the endoderm.|||Belongs to the yippee family.|||May play a role in epithelioid conversion of fibroblasts.|||Nucleus http://togogenome.org/gene/10090:Rusf1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B5|||http://purl.uniprot.org/uniprot/Q91W34 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the RUS1 family.|||Membrane http://togogenome.org/gene/10090:Saraf ^@ http://purl.uniprot.org/uniprot/A0A0R4J0D1|||http://purl.uniprot.org/uniprot/Q8R3Q0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SARAF family.|||Endoplasmic reticulum membrane|||Interacts with STIM1; the interaction is inhibit by th interaction of STIM1 with EFHB.|||Membrane|||Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions (By similarity).|||Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions.|||The cytoplasmic C-terminal region mediates interaction with STIM1, while the N-terminal lumenal region mediates regulation of SOCE activity. http://togogenome.org/gene/10090:Capn3 ^@ http://purl.uniprot.org/uniprot/A4QPE6|||http://purl.uniprot.org/uniprot/Q0VGP9|||http://purl.uniprot.org/uniprot/Q64691 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by micromolar concentrations of calcium and inhibited by calpastatin.|||Belongs to the peptidase C2 family.|||Calcium-regulated non-lysosomal thiol-protease.|||Calcium-regulated non-lysosomal thiol-protease. Proteolytically cleaves CTBP1 at 'His-410'. Mediates, with UTP25, the proteasome-independent degradation of p53/TP53.|||Cytoplasm|||Homodimer.|||Homodimer; via EF-hand domain 4. Interacts with TTN/titin. Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis. Interacts with SIMC1. Interacts with UTP25; the interaction is required for CAPN3 translocation to the nucleolus.|||nucleolus http://togogenome.org/gene/10090:Osbpl10 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0F9|||http://purl.uniprot.org/uniprot/S4R1M9|||http://purl.uniprot.org/uniprot/S4R296 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OSBP family.|||Interacts with OSBPL9. Interacts with DIAPH1.|||Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P. Plays a role in negative regulation of lipid biosynthesis. Negatively regulates APOB secretion from hepatocytes. Binds cholesterol and acidic phospholipids. Also binds 25-hydroxycholesterol. Binds phosphatidylserine.|||The C-terminal region binds cholesterol, 25-hydroxysterol and acidic phospholipids and is required for localization to microtubules.|||The PH domain selectively interacts with phosphatidylinositol-4-phosphate.|||cytoskeleton http://togogenome.org/gene/10090:Slc25a26 ^@ http://purl.uniprot.org/uniprot/Q5U680 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial S-adenosyl-L-methionine/S-adenosyl-L-homocysteine antiporter. Mediates the exchange of cytosolic S-adenosyl-L-methionine, the predominant methyl-group donor for macromolecule methylation processes, for mitochondrial S-adenosylhomocysteine(SAH), a by-product of methylation reactions.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Rnmt ^@ http://purl.uniprot.org/uniprot/Q9D0L8 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0 methyltransferase family.|||Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Binds RNA containing 5'-terminal GpppC.|||Interacts with importin alpha, leading to stimulate both RNA-binding and methyltransferase activity. Interaction with importin alpha and beta is required for its nuclear localization, importin beta dissociating in response to RanGTP, allowing RNMT-importin alpha to bind RNA substrates. Interacts with elongating form of polymerase II and RNGTT. Interacts with RAMAC, this interaction significantly enhances RNA-binding and cap methyltransferase activity.|||Methyltransferase activity is activated by RAMAC.|||Nucleus http://togogenome.org/gene/10090:Glod5 ^@ http://purl.uniprot.org/uniprot/Q9D8I3 ^@ Similarity ^@ Belongs to the glyoxalase I family. http://togogenome.org/gene/10090:Stmn4 ^@ http://purl.uniprot.org/uniprot/D3Z4C2|||http://purl.uniprot.org/uniprot/G3X9Z6|||http://purl.uniprot.org/uniprot/P63042|||http://purl.uniprot.org/uniprot/Q05DI3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the stathmin family.|||Exhibits microtubule-destabilizing activity.|||Golgi apparatus|||axon|||growth cone http://togogenome.org/gene/10090:Sh3gl2 ^@ http://purl.uniprot.org/uniprot/Q62420 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes (By similarity). The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface.|||Belongs to the endophilin family.|||Cytoplasm|||Early endosome|||Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth (PubMed:21849472). Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes (PubMed:21849472).|||Membrane|||Monomer; in cytoplasm. Homodimer; when associated with membranes (By similarity). Interacts with SYNJ1 (By similarity). Interacts with DNM1 (PubMed:10490020). Interacts with MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK activation (By similarity). Interacts with OPHN1 (PubMed:19481455). Interacts with PDCD6IP (By similarity). Interacts with BIN2 (By similarity). Interacts with ATXN2 (PubMed:18602463). Interacts with ADAM9 and ADAM15 cytoplasmic tails (PubMed:10531379). Interacts with TMEM108 (PubMed:21849472). Interacts with ADGRB2 (PubMed:28891236).|||Presynapse|||Was originally thought to have lysophosphatidic acid acyltransferase activity, but has since been experimentally shown not to have this activity. http://togogenome.org/gene/10090:Cdc42 ^@ http://purl.uniprot.org/uniprot/P60766 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.|||Cell membrane|||Cytoplasm|||Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent manner) (PubMed:10490598, PubMed:10934474). Interacts with activated CSPG4 and with BAIAP2 (By similarity). Interacts with DOCK11/Zizimin2; the interaction activates CDC42 by exchanging GDP for GTP (PubMed:15710388, PubMed:16968698). Interacts with DOCK9; the interaction activates CDC42 by exchanging GDP for GTP (By similarity). Interacts with DOCK8 (via DHR-2 domain); the interaction activates CDC42 by exchanging GDP for GTP (PubMed:22461490). Interacts with IQGAP1 (PubMed:16968698). Interacts with NET1 and ARHGAP33/TCGAP (PubMed:9535835, PubMed:12773384). Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ (PubMed:10934474). The GTP-bound form interacts with CCPG1 (PubMed:17000758). Interacts with USP6 (By similarity). Interacts with NEK6 (By similarity). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas (By similarity). Interacts with ITGB1BP1 (By similarity). Interacts with ARHGDIA; this interaction inactivates and stabilizes CDC42. Interacts with ARHGDIB; this maintains CDC42 in the inactive, GDP-bound form (By similarity). Interacts in (GTP-bound form) with FNBP1L and ABI1, but only in the presence of FNBP1L (By similarity).|||Midbody|||Phosphorylated by SRC in an EGF-dependent manner, this stimulates the binding of the Rho-GDP dissociation inhibitor RhoGDI.|||Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:24352656). In its active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Regulates cell migration (By similarity). In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections. Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons (PubMed:25851601). Facilitates filopodia formation upon DOCK11-activation (PubMed:22494997). Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups (By similarity).|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Inhibited by GAPs such as ARHGAP44 (PubMed:24352656, PubMed:26969129).|||centrosome|||dendrite|||lamellipodium membrane|||spindle http://togogenome.org/gene/10090:Metap1d ^@ http://purl.uniprot.org/uniprot/Q9CPW9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.|||Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.|||Mitochondrion|||Removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed. http://togogenome.org/gene/10090:Adhfe1 ^@ http://purl.uniprot.org/uniprot/Q8R0N6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.|||Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). L-3-hydroxybutyrate (L-3-OHB) is also a substrate for HOT when using 2-KG as hydrogen acceptor, resulting in the formation of D-2-HG (By similarity).|||Down-regulated of 40% in white adipose tissue of ob/ob obese mice.|||Expressed in white and brown adipose tissues, liver, and kidney. Expression is differentiation-dependent during in vitro brown and white adipogenesis.|||Mitochondrion http://togogenome.org/gene/10090:Atp6ap1l ^@ http://purl.uniprot.org/uniprot/D3Z5W0 ^@ Similarity ^@ Belongs to the vacuolar ATPase subunit S1 family. http://togogenome.org/gene/10090:Eif1b ^@ http://purl.uniprot.org/uniprot/Q9CXU9 ^@ Function|||Similarity ^@ Belongs to the SUI1 family.|||Probably involved in translation. http://togogenome.org/gene/10090:Pfdn5 ^@ http://purl.uniprot.org/uniprot/Q9WU28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prefoldin subunit alpha family.|||Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. Represses the transcriptional activity of MYC (By similarity).|||Heterohexamer of two PFD-alpha type and four PFD-beta type subunits.|||Nucleus http://togogenome.org/gene/10090:Agpat1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J263|||http://purl.uniprot.org/uniprot/O35083 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.|||Endoplasmic reticulum membrane|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||Widely expressed. http://togogenome.org/gene/10090:Capn6 ^@ http://purl.uniprot.org/uniprot/O35646|||http://purl.uniprot.org/uniprot/Q80VZ1 ^@ Caution|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 10.5 dpc expressed in the mandibular arches, heart and limb buds.|||Belongs to the peptidase C2 family.|||Interacts (via domain III) with microtubules. Interacts (via domain II) with ARHGEF2 (via the N-terminal zinc finger).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Microtubule-stabilizing protein that may be involved in the regulation of microtubule dynamics and cytoskeletal organization. May act as a regulator of RAC1 activity through interaction with ARHGEF2 to control lamellipodial formation and cell mobility. Does not seem to have protease activity as it has lost the active site residues.|||Up-regulated during the osteoclasogenic process. Inhibited by dexamethaxone during the osteoclasogenic process.|||perinuclear region|||spindle http://togogenome.org/gene/10090:Nsun3 ^@ http://purl.uniprot.org/uniprot/Q8CCT7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.|||Mitochondrial tRNA methyltransferase that mediates methylation of cytosine to 5-methylcytosine (m5C) at position 34 of mt-tRNA(Met). mt-tRNA(Met) methylation at cytosine(34) takes place at the wobble position of the anticodon and initiates the formation of 5-formylcytosine (f(5)c) at this position. mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation.|||Mitochondrion matrix http://togogenome.org/gene/10090:H3f3a ^@ http://purl.uniprot.org/uniprot/P84244 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed throughout the cell cycle independently of DNA synthesis.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes. metaphase chromosomes.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains (By similarity). Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).|||Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 and Lys-80. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with HIRA, a chaperone required for its incorporation into nucleosomes. Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3). Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity). Interacts with ASF1A, MCM2, NASP and SPT2 (By similarity).|||Ubiquitinated. Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.|||Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. http://togogenome.org/gene/10090:F2 ^@ http://purl.uniprot.org/uniprot/P19221|||http://purl.uniprot.org/uniprot/Q3TJ94 ^@ Activity Regulation|||Caution|||Function|||Miscellaneous|||PTM|||Similarity|||Subunit ^@ Belongs to the peptidase S1 family.|||Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5. In plasma, interacts (via N-terminus) with alpha-1-microglobulin; this interaction does not prevent the activation of prothrombin to thrombin.|||In the penultimate step of the coagulation cascade, prothrombin is converted to thrombin by the prothrombinase complex composed of factor Xa (F10), cofactor Va (F5), and phospholipids. This activation requires factor Xa-catalyzed sequential cleavage at 2 sites, Arg-311 and Arg-360, along 2 possible pathways. In the first pathway, the first cleavage occurs at Arg-311, leading to the formation of the inactive intermediate prethrombin-2. This pathway preferentially occurs on platelets and in the absence of cofactor Va. In the second pathway, the first cleavage occurs at Arg-360, which separates protease domain into 2 chains that remain connected through a disulfide bond and generates the active intermediate meizothrombin. The presence of cofactor Va directs activation along the meizothrombin pathway and greatly accelerates the rate of cleavage at Arg-360, but has a smaller effect on the cleavage of meizothrombin at Arg-311. Meizothrombin accumulates as an intermediate when prothrombinase is assembled on the membrane of red blood cells.|||Inhibited by SERPINA5.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin.|||Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa.|||Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity).|||Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. http://togogenome.org/gene/10090:Or14a258 ^@ http://purl.uniprot.org/uniprot/Q7TS03 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trim30d ^@ http://purl.uniprot.org/uniprot/E9PWL0 ^@ Similarity ^@ Belongs to the TRIM/RBCC family. http://togogenome.org/gene/10090:F7 ^@ http://purl.uniprot.org/uniprot/P70375|||http://purl.uniprot.org/uniprot/Q542C2 ^@ Caution|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Can be either O-glucosylated or O-xylosylated at Ser-93 by POGLUT1.|||Expression in the liver and plasma oscillates in a circadian manner.|||Heterodimer of a light chain and a heavy chain linked by a disulfide bond.|||Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Plasma and liver.|||Secreted|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.|||The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium. http://togogenome.org/gene/10090:Zfta ^@ http://purl.uniprot.org/uniprot/Q4VA45 ^@ Sequence Caution ^@ Aberrant splicing. http://togogenome.org/gene/10090:Prdm2 ^@ http://purl.uniprot.org/uniprot/A2A7B5|||http://purl.uniprot.org/uniprot/B9EKQ3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Mpst ^@ http://purl.uniprot.org/uniprot/Q99J99 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By oxidative stress, and thioredoxin. Under oxidative stress conditions, the catalytic cysteine site is converted to a sulfenate which inhibits the MPST enzyme activity. Reduced thioredoxin cleaves an intersubunit disulfide bond to turn on the redox switch and reactivate the enzyme. Inhibited by different oxidants, hydrogen peroxide and tetrathionate.|||Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue (By similarity).|||Cytoplasm|||Expressed in the brain and retina. In the retina, localized to the inner and outer plexiform layer, the inner and outer nuclear layer and the outer segments of photoreceptors. In the brain, localized to neurons of mitral cell layers, glomerular, and external plexiform layers in the olfactory bulb. Also found in Purkinje cell stomata and proximal dendrites. In the spinal cord, localized to large neurons. In the cerebral cortex, localized to pyramidial neurons in layers II/III and V, and in layers I-VI of neocortical areas. In the hippocampus, found in CA1 and CA3 pyramidal cells.|||In the developing brain, maintained expression from 16 dpc to postnatal day 14. Levels decrease between postnatal day 28 and postnatal day 52 and increase again with further aging up to 156 days old.|||Mitochondrion|||Monomer (active form). Homodimer; disulfide-linked (inactive form).|||Thioredoxin (Trx) or dihydrolipoic acid (DHLA) are required to release hydrogen sulfide from the persulfide intermediate.|||Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions.|||synaptosome http://togogenome.org/gene/10090:Tnxb ^@ http://purl.uniprot.org/uniprot/A0A5F8MPH8|||http://purl.uniprot.org/uniprot/E9Q2T3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tenascin family.|||extracellular matrix http://togogenome.org/gene/10090:Ifnlr1 ^@ http://purl.uniprot.org/uniprot/Q8CGK5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II cytokine receptor family.|||Heterodimer with IL10RB.|||Membrane|||The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state. Determines the cell type specificity of the lambda interferon action. Shows a more restricted pattern of expression in the epithelial tissues thereby limiting responses to lambda interferons primarily to epithelial cells of the respiratory, gastrointestinal, and reproductive tracts. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium.|||The mice are viable and appear to be of normal size, behavior and reproductive ability. There is no effect on the ability to combat vaginal viral infection, but antiviral response evoked by Toll-like reseptor (TLR) stimulation is reduced. Mice also display enhanced rotavirus susceptibility associated with epithelial vacuolization, villus deformation and epithelial cell disruption.|||Ubiquitinated by FBXO45-containing E3 ligase leading to proteasomal degradation. http://togogenome.org/gene/10090:Krtap16-3 ^@ http://purl.uniprot.org/uniprot/Q8C1I6 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 16 family.|||Expression in skin and hair follicle is regulated by HOXC13 and by GATA3.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins.|||Strong expression in narrowly defined pattern restricted to the lower and middle cortical regions of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). http://togogenome.org/gene/10090:Stradb ^@ http://purl.uniprot.org/uniprot/Q8K4T3 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. Interacts with BIRC4/XIAP. These two proteins are likely to coexist in a complex with TAK1, TRAF6, TAB1 and TAB2 (By similarity).|||Cytoplasm|||Nucleus|||Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation (By similarity).|||Ser-184 is present instead of the conserved Asp which is expected to be an active site residue.|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Ttc27 ^@ http://purl.uniprot.org/uniprot/Q8CD92 ^@ Similarity ^@ Belongs to the TTC27 family. http://togogenome.org/gene/10090:Mtx2 ^@ http://purl.uniprot.org/uniprot/O88441|||http://purl.uniprot.org/uniprot/Q8C454 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metaxin family.|||Interacts with MTX1/metaxin-1. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex (By similarity).|||Involved in transport of proteins into the mitochondrion.|||Membrane|||Mitochondrion|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Zbtb8a ^@ http://purl.uniprot.org/uniprot/Q9CWH1 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Rfc2 ^@ http://purl.uniprot.org/uniprot/Q4KL82|||http://purl.uniprot.org/uniprot/Q9WUK4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the activator 1 small subunits family.|||Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA. RFC2 also interacts with PRKAR1A; the complex may be involved in cell survival. Interacts with DDX11.|||Nucleus|||The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. This subunit binds ATP (By similarity). http://togogenome.org/gene/10090:Ms4a10 ^@ http://purl.uniprot.org/uniprot/Q99N03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed in thymus, kidney, colon, brain and testis. Expressed also by various hematopoietic and lymphoblastoid cell lines.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Mkrn2 ^@ http://purl.uniprot.org/uniprot/Q9ERV1 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:28378844). Promotes the polyubiquitination and proteasome-dependent degradation of RELA/p65, thereby suppressing RELA-mediated NF-kappa-B transactivation and negatively regulating inflammatory responses (PubMed:28378844). Plays a role in the regulation of spermiation and in male fertility (PubMed:28008940).|||Highly expressed in the testis, and lower expression in the brain, thymus, heart, lung, liver, spleen, kidney, ovary, uterus, and seminal vesicle (at protein level) (PubMed:28008940). Expressed in primary immune cells, such as CD4-positive and CD8-positive T cells, CD19-positive B cells and CD11c-positive dendritic cells, and in embryonic fibroblasts (at protein level) (PubMed:28378844).|||Interacts with PDLIM2 (via LIM zinc-binding domain) (PubMed:28378844). Interacts with RELA (PubMed:28378844).|||Male and female knockout mice are viable with a lighter birthweight than wild-type animals (PubMed:28008940). Causes infertility in male mice, whereas female mice are fertile, but display reduced fecundity (PubMed:28008940). Leads to abnormal sperms characterized by low number, poor motility, and aberrant morphology (PubMed:28008940). Sperms have deformed heads with abnormal or missing acrosomes, disorganized axonemal structure, and disorganized flagellar structure (PubMed:28008940). Complete loss of the axoneme doublets in one side of the fibrous sheath and disordered assembly of axoneme doublets (PubMed:28008940). Causes failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization in testes, thus impairing spermiogenesis and spermiation (PubMed:28008940). Disrupted arrangement of ectoplasmic specialization, the adhesion junction found in Sertoli cells at sites of attachment to elongated spermatids or neighboring Sertoli cells in the testes, and decreased expression of Espn (PubMed:28008940). The outer dense fiber, which is an important component of flagellae, is absent or improperly arranged in epididymal sperms (PubMed:28008940). Decreased expression levels of Odf2 in spermatogenesis (PubMed:28008940).|||Nucleus http://togogenome.org/gene/10090:Camkmt ^@ http://purl.uniprot.org/uniprot/B9EHP1|||http://purl.uniprot.org/uniprot/Q3U2J5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. CLNMT methyltransferase family.|||Catalyzes the trimethylation of 'Lys-116' in calmodulin.|||Cytoplasm|||Detected in most of the tissues examined, with the highest expression in the brain and muscle (at protein level).|||Golgi apparatus|||Monomer. Interacts with HSP90, probably as a client (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fcf1 ^@ http://purl.uniprot.org/uniprot/Q9CTH6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UTP23/FCF1 family. FCF1 subfamily.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Noa1 ^@ http://purl.uniprot.org/uniprot/Q9JJG9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, weak but widespread expression. By 12.5 dpc prominently expressed in the liver and also detected in developing CNS and dorsal root ganglia. At 14.5 dpc, expression is intensified in bone.|||Belongs to the TRAFAC class YlqF/YawG GTPase family. NOA1 subfamily.|||Expressed in tissues associated with high mitochondria content including testes, heart, liver, brain and thymus. Also expressed in various bone cell lines.|||Homodimer or multimer. Interacts with mitochondrial complex I, DAP3, MRPL12 and MRPS27.|||Involved in regulation of mitochondrial protein translation and respiration. Plays a role in mitochondria-mediated cell death. May act as a scaffolding protein or stabilizer of respiratory chain supercomplexes. Binds GTP.|||Mice display mid-gestation lethality associated with a severe developmental defect of the embryo and trophoblast. Primary embryonic fibroblasts isolated from mutant 9.5 dpc embryos show deficient mitochondrial synthesis and a global defect of oxidative phosphorylation.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Fcrla ^@ http://purl.uniprot.org/uniprot/Q920A9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in spleen. Expressed in immature B-cell and B-cell lines.|||May be implicated in B-cell differentiation and lymphomagenesis.|||Monomer or homodimer; disulfide-linked. http://togogenome.org/gene/10090:Sort1 ^@ http://purl.uniprot.org/uniprot/Q6PHU5 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VPS10-related sortilin family. SORT1 subfamily.|||Cell membrane|||During adipocyte differentiation.|||Endoplasmic reticulum membrane|||Endosome membrane|||Expressed in the brain, particularly the piriform cortex, the cerebral cortex and the hippocampus.|||Expressed in the ectoderm at 7.5 dpc and within the germ cell layers at 8.5 dpc. Expressed within the neural epithelium and the neural tube at 9.5 dpc and subsequently expressed in the nervous system throughout development. Expression in the proliferative zones of the central nervous system declines between 14.5 dpc and 16.5 dpc, while expression remains high in the cerebral cortex and the neural retina. Expressed in the pituitary and the sensory epithelia throughout development.|||Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Lysosomal proteins bind specifically to the receptor in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.|||Golgi stack membrane|||Interacts with the cytosolic adapter proteins GGA1 and GGA2. Interacts with numerous ligands including the receptor-associated protein LRPAP1/RAP, NTS and GM2A. Forms a complex with NGFR which binds specifically to the precursor forms of NGFB (proNGFB) and BDNF (proBDNF). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; may regulate their anterograde axonal transport and signaling (By similarity). Interacts with LPL (PubMed:10085125). Interacts with PSAP (PubMed:15236332). Interacts with SLC2A4 (PubMed:15992544). Interacts with NRADD and NGFR (PubMed:19407813). Interaction with NRADD protects against degradation in the lysosome. Interacts with CLN5 (By similarity). Interacts with GRN; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system (By similarity). Interacts with the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus (By similarity). Interacts with SMPD1; the interaction is required for SMPD1 targeting to lysosomes (By similarity).|||Lysosome membrane|||Nucleus membrane|||Palmitoylated. Undergoes cysteine S-palmitoylation which promotes the partitioning of the receptor into an endosomal membrane subdomain where it can interact with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus.|||Phosphorylation at Ser-819 facilitates the interaction with GGA1.|||The N-terminal propeptide is cleaved by furin and possibly other homologous proteases.|||The N-terminal propeptide may facilitate precursor transport within the Golgi stack. Intrachain binding of the N-terminal propeptide and the extracellular domain may also inhibit premature ligand binding (By similarity).|||The extracellular domain may be shed following protease cleavage in some cell types. http://togogenome.org/gene/10090:Stk4 ^@ http://purl.uniprot.org/uniprot/Q9JI11 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183. It also diminishes its cleavage by caspases and its ability to phosphorylate FOXO3 (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RASSF1. Interacts with FOXO3. Interacts with RASSF2 (via SARAH domain). Interacts with AR, PKB/AKT1, TNNI3 and SIRT1. Interacts with MARK3 and SCRIB in the presence of DLG5 (By similarity). Interacts with DLG5 (via PDZ domain 3) (PubMed:28087714).|||Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-183. Activated by RASSF1 which acts by preventing its dephosphorylation (By similarity).|||Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age.|||Nucleus|||Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 resulting in a 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N).|||Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes (By similarity). http://togogenome.org/gene/10090:Rpgrip1l ^@ http://purl.uniprot.org/uniprot/Q8CG73 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RPGRIP1 family.|||Cytoplasm|||Expression was detected throughout embryonic development as early as 8.5 dpc.|||Interacts with NPHP4 and NPHP1; NPHP1, NPHP4 and RPGRIP1L are proposed to form a functional NPHP1-4-8 module localized to cell-cell contacts and the ciliary transition zone; NPHP4 mediates the interaction between NPHP1 and RPGRIP1L. Interacts with IQCB1; the interaction likely requires additional interactors (PubMed:21565611). Interacts with TBXA2R (via C-terminus), RPGR, NEK4. Interacts with NPHP4, INVS and DVL2; proposed to form a complex involved in DVL2 stabilization (By similarity). Interacts with PSMD2 (PubMed:26150391).|||Negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R) (By similarity). May be involved in mechanisms like programmed cell death, craniofacial development, patterning of the limbs, and formation of the left-right axis. Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module. Does not seem to be strictly required for ciliogenesis (By similarity). Involved in establishment of planar cell polarity such as in cochlear sensory epithelium and is proposed to implicate stabilization of disheveled proteins (PubMed:22927466). Involved in regulation of proteasomal activity at the primary cilium probably implicating association with PSDM2 (PubMed:26150391).|||Ubiquitously expressed. Not found in heart and skin.|||centrosome|||cilium axoneme|||cilium basal body|||tight junction http://togogenome.org/gene/10090:Prrx2 ^@ http://purl.uniprot.org/uniprot/A2APZ7|||http://purl.uniprot.org/uniprot/Q06348 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||In the embryo, expressed in craniofacial mesenchyme, limb, heart, somites and sclerotomes. Absent from central and peripheral nervous systems, splanchnopleure and ectodermal derivatives.|||Nucleus http://togogenome.org/gene/10090:Lcmt1 ^@ http://purl.uniprot.org/uniprot/A2RTH5 ^@ Function|||Similarity ^@ Belongs to the methyltransferase superfamily. LCMT family.|||Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues. http://togogenome.org/gene/10090:Arhgef9 ^@ http://purl.uniprot.org/uniprot/Q3UTH8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters (By similarity).|||Cytoplasm|||Detected in embryonic and adult brain.|||Interacts with GPHN.|||Postsynaptic density http://togogenome.org/gene/10090:Serpinb3b ^@ http://purl.uniprot.org/uniprot/Q9D1Q5 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Gemin6 ^@ http://purl.uniprot.org/uniprot/Q9CX53 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Interacts with GEMIN7; the interaction is direct. Interacts with GEMIN8; the interaction is direct. Interacts with SNRPB, SNRPD2, SNRPD3 and SNRPE; the interaction is direct.|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (By similarity).|||gem|||nucleoplasm http://togogenome.org/gene/10090:Dgkd ^@ http://purl.uniprot.org/uniprot/E9PUQ8 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Cell membrane|||Cytoplasm|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:17021016). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:17021016). By controlling the levels of diacylglycerol, regulates for instance the PKC and EGF receptor signaling pathways and plays a crucial role during development (PubMed:17021016). May also regulate clathrin-dependent endocytosis (By similarity).|||Homooligomer. Monomer. Interacts with AP2A2; regulates clathrin-dependent endocytosis.|||Homozygous knockout of dgkd is lethal (PubMed:17021016). Fetuses are smaller and newborn mice develop respiratory difficulty and die within 24 hours after birth (PubMed:17021016). They show an abnormal open-eyelids phenotype which is associated with significant reduction of the expression of the EGF receptor/EGFR in the basal layer of the epidermis (PubMed:17021016).|||The PH domain mediates association with membranes.|||The SAM domain mediates homooligomerization.|||Widely expressed.|||clathrin-coated pit http://togogenome.org/gene/10090:Taf6 ^@ http://purl.uniprot.org/uniprot/Q62311 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF6 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts directly with TBP, TAF1/TAFII250, TAF9/TAFII31 and TAF12/TAFII20. The TAF6/TAFII70-TAF9/TAFII31 heterodimer forms an octamer complex with the TAF4B/TFII105-TAF12/TFIID20 heterodimer. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Also interacts with the GTFs, TFIIEalpha/GTF2E1 and TFIIFalpha/GTF2F1. Component of the TBP-free TAFII-histone acetylase complex (TFTC-HAT) (By similarity). Interacts with TP53/p53 (By similarity).|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TAF6 homodimer connects TFIID modules, forming a rigid core. http://togogenome.org/gene/10090:Pnp ^@ http://purl.uniprot.org/uniprot/P23492|||http://purl.uniprot.org/uniprot/Q543K9 ^@ Disruption Phenotype|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 10-week old, mice have a smaller cerebellum, corpus callosum and thalamus and motor abnormalities (PubMed:22521465). Normal number of Purkinje cells in the cerebellum at birth but numbers start to decrease as mice get older (PubMed:22521465). Purkinje cells in the cerebellum have an irregular shape, a granular cytoplasm and degenerated dendrites characterized by fewer dendritic spines processes (PubMed:22521465). Loss of inosine phosphorylase activity in cerebellum, liver and kidney (PubMed:22521465). In the thymus, causes a 2-fold increase in the frequency of immature CD4(-) CD8(-) double negative (DN) thymocytes and a decrease in the total cell numbers of CD4(+)CD8(+) double positive (DP), and CD4(+) and CD8(+) single positive (SP) thymocytes due to an increase in apoptosis (PubMed:10859343). In the spleen and lymph nodes, numbers of CD4(+) and CD8(+) T-cells are reduced and the frequency of immature CD19(+)IgM(+) pre-B cells is increased without affecting the frequency of IgM(+) mature B-cells (PubMed:10859343). In the spleen, numbers of myeloid cells are also increased (PubMed:10859343). In thymocytes, mitochondrial dGTP levels are increased, and GTP levels and deoxyguanosine kinase activity are reduced (PubMed:10859343). Accumulation of dGTP in the mitochondria of thymocytes is probably causing thymocyte apoptosis by interfering with the repair of mitochondrial DNA damage (PubMed:10859343). Cytotoxic T-cells-mediated killing is impaired in absence of IL2 (PubMed:10859343). In urine, levels of inosine, deoxyinosine, guanosine, and deoxyguanosine are increased (PubMed:10859343).|||Belongs to the PNP/MTAP phosphorylase family.|||Catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (PubMed:10859343) (Probable). Preferentially acts on 6-oxopurine nucleosides including inosine and guanosine (Probable).|||Cytoplasm|||Four electrophoretic alleles of NP are known; NPA (shown here), NPB, NPC and NPD.|||Homotrimer.|||The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. http://togogenome.org/gene/10090:Cdk8 ^@ http://purl.uniprot.org/uniprot/Q8R3L8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II. Interacts with CTNNB1, GLI3 and MAML1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm21462 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Fcmr ^@ http://purl.uniprot.org/uniprot/A1KXC4 ^@ Domain|||Function|||Subcellular Location Annotation ^@ May play a role in the immune system processes. Protects cells from FAS-, TNF alpha- and FADD-induced apoptosis without increasing expression of the inhibitors of apoptosis BCL2 and BCLXL. Seems to activate an inhibitory pathway that prevents CASP8 activation following FAS stimulation, rather than blocking apoptotic signals downstream. May inhibit FAS-induced apoptosis by preventing CASP8 processing through CFLAR up-regulation (By similarity).|||Membrane|||The Ig-like domain is required for the anti-apoptotic ability. http://togogenome.org/gene/10090:Or2a52 ^@ http://purl.uniprot.org/uniprot/Q8VEV1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ebf1 ^@ http://purl.uniprot.org/uniprot/Q07802|||http://purl.uniprot.org/uniprot/Q3UTW6|||http://purl.uniprot.org/uniprot/Q5SWK4|||http://purl.uniprot.org/uniprot/Q5SWK5|||http://purl.uniprot.org/uniprot/Q8CBL7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the COE family.|||Expressed at high levels in early B-cells, spleen, lymph node and adipose tissue, and at low levels in heart, brain, skeletal muscle and kidney. In adult expressed in olfactory epithelium, in spleen, and at a lesser extent in Purkinje cells of the cerebellum, heart, kidney, lung, thymus and testis. In embryo expressed in dorsal thalamus and epithalamus, at a lower level in mesencephalon and in the caudal rhombencephalon, in the postmitotic cells of developing retina, highly in developing spinal cord, dorsal root ganglia, trigeminal ganglia and in glossopharyngeal nerve ganglia, in developing inner ear.|||First detected at 9.5 dpc.|||Homodimer (PubMed:9151732, PubMed:20876732). Interacts with ZNF423 and ZNF521, leading to prevent EBF1 to bind DNA and activate target genes (By similarity). Interacts with CCR4-NOT component CNOT3 (By similarity).|||Key pioneer transcription factor of B-cell specification and commitment (PubMed:1915300, PubMed:7542362, PubMed:23812095). Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3' (PubMed:20876732). Operates in a transcription factor network to activate B-cell-specific genes and repress genes associated with alternative cell fates (PubMed:23812095, PubMed:20451411). For instance, positively regulates many B-cell specific genes including BCR or CD40 while repressing genes that direct cells into alternative lineages, including GATA3 and TCF7 for the T-cell lineage (PubMed:23812095, PubMed:20451411). In addition to its role during lymphopoiesis, controls the thermogenic gene program in adipocytes during development and in response to environmental cold (PubMed:32130892).|||Nucleus|||Targeted disruption in mice results in animals with a severe defect in early B-cell development. EBF1 heterozygous mice exhibit an approximately 2-fold decrease in the number of cells in the pro-B lymphocyte compartment, indicating that normal B-cell development depends on the presence of two wild-type EBF1 alleles (PubMed:7542362). Adipocyte-specific deletion mutant reveals a modest reduction of UCP1 expression, a mitochondrial protein responsible for thermogenic respiration. Double mutants EBF1/EBF2 show a more severe reduction of UCP1 expression (PubMed:32130892). http://togogenome.org/gene/10090:Trmt5 ^@ http://purl.uniprot.org/uniprot/Q9D0C4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.|||Cytoplasm|||Involved in mitochondrial tRNA methylation (By similarity). Specifically methylates the N1 position of guanosine-37 in various tRNAs. Methylation is not dependent on the nature of the nucleoside 5' of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding.|||Mitochondrion matrix|||Monomer.|||Nucleus http://togogenome.org/gene/10090:Firrm ^@ http://purl.uniprot.org/uniprot/Q3TQQ9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts (via its N-terminal region) with PLK1; controls PLK1 kinase activity. Interacts (via the KVVXF motif) with PPP1CC; controls PLK1 kinase activity. Interacts with FIGNL1; may regulate homologous recombination.|||Midbody|||Nucleus|||Phosphorylation at Ser-101 by PLK1 strengthens FIRRM-PLK1 interaction. Phosphorylation at Ser-795 by PLK1 negatively regulates its interaction with PPP1CC.|||Regulates PLK1 kinase activity at kinetochores and promotes faithful chromosome segregation in prometaphase by bridging kinase and phosphatase activities. Phosphorylation of FIRRM by PLK1 negatively regulates its interaction with the phosphatase, PPP1CC, thus creating a negative feedback loop for maintaining proper PLK1 kinase activity during mitosis. In complex with FIGL1 may regulate homologous recombination.|||centromere|||kinetochore|||spindle http://togogenome.org/gene/10090:Cast ^@ http://purl.uniprot.org/uniprot/A0A1Y7VJN8|||http://purl.uniprot.org/uniprot/P51125|||http://purl.uniprot.org/uniprot/Q3TTN2|||http://purl.uniprot.org/uniprot/Q8C281|||http://purl.uniprot.org/uniprot/Q8CB83|||http://purl.uniprot.org/uniprot/Q8CE04|||http://purl.uniprot.org/uniprot/Q8CE80|||http://purl.uniprot.org/uniprot/Q921U7 ^@ Domain|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the protease inhibitor I27 (calpastatin) family.|||Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site.|||Isoform 2 is the major form in all tissues examined. Isoform 1 accounts for 5-10% in tissues such as skeletal muscle, liver and brain, and 30% in myoblasts. Isoforms 4 and 5 are testis-specific. Isoform 6 is highly expressed in heart and skeletal muscle with lower levels in liver, brain and testis. Isoform 7 is expressed at high levels in liver.|||Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue. http://togogenome.org/gene/10090:Or2ah1 ^@ http://purl.uniprot.org/uniprot/A2ASV3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or8k3 ^@ http://purl.uniprot.org/uniprot/Q8VGS0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lipo3 ^@ http://purl.uniprot.org/uniprot/Q3UT41 ^@ Similarity ^@ Belongs to the AB hydrolase superfamily. Lipase family. http://togogenome.org/gene/10090:Mphosph8 ^@ http://purl.uniprot.org/uniprot/Q3TYA6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expressed in the spermatogonia, spermatocytes and granular cells within the cerebellum.|||Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression. Mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2. Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates down-regulation of CDH1 expression. Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed.|||Homodimer. Interacts (via chromo domain) with histone H3K9me3. Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2 and H3K9me1. Component of the HUSH complex; at least composed of TASOR, PPHLN1 and MPHOSPH8. Interacts with DNMT3, EHMT1 and SETDB1. Interacts with MORC2; the interaction associateS MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci. Interacts with ZNF638; leading to recruitment of the HUSH complex to unintegrated retroviral DNA (By similarity). Interacts with TASOR (PubMed:31112734).|||Nucleus|||Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin.|||The chromo domain mediates interaction with methylated 'Lys-9' of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3). http://togogenome.org/gene/10090:Zkscan2 ^@ http://purl.uniprot.org/uniprot/G3X952 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Rnf144b ^@ http://purl.uniprot.org/uniprot/Q8BKD6 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated.|||Belongs to the RBR family. RNF144 subfamily.|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates such as LCMT2, thereby promoting their degradation. Induces apoptosis via a p53/TP53-dependent but caspase-independent mechanism. However, its overexpression also produces a decrease of the ubiquitin-dependent stability of BAX, a pro-apoptotic protein, ultimately leading to protection of cell death; But, it is not an anti-apoptotic protein per se (By similarity).|||Interacts with UBE2L3, UBE2L6 and LCMT2 as well as with BAX.|||Lacks the His residue in the RING-type domain 2 that is one of the conserved features of the family.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.|||Mitochondrion membrane http://togogenome.org/gene/10090:Wdr43 ^@ http://purl.uniprot.org/uniprot/Q6ZQL4 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UTP5 family.|||Detected at low levels at least in heart, liver, lung, spleen, thymus and hippocampus.|||Expressed during embryonic development, expression decreases at morula stage.|||N-terminal domain is required for nucleoplasm location and C-terminal domain for nucleolus location.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity). May be a component of the proposed t-UTP subcomplex of the ribosomal small subunit (SSU) processome containing at least UTP4, WDR43, HEATR1, UTP15, WDR75 (By similarity). Binds to RNA; binding is required for its chromatin association (PubMed:31128943). Interacts with CDK9, DDX21 and SUPT6H (PubMed:31128943). Interacts with RNA polymerase II (PubMed:31128943). Interacts directly with UTP4 and UTP15 (By similarity).|||Ribosome biogenesis factor that coordinates hyperactive transcription and ribogenesis. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I (By similarity). Essential for stem cell pluripotency and embryonic development (PubMed:31128943). In the nucleoplasm, recruited by promoter-associated/nascent transcripts and transcription to active promoters where it facilitates releases of elongation factor P-TEFb and paused RNA polymerase II to allow transcription elongation and maintain high-level expression of its targets genes (PubMed:31128943).|||nucleolus|||nucleolus fibrillar center|||nucleoplasm http://togogenome.org/gene/10090:Slc29a1 ^@ http://purl.uniprot.org/uniprot/Q3TCZ2|||http://purl.uniprot.org/uniprot/Q9JIM1 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.|||Cell membrane|||Cys-418 near TM10 is a major determinant of nucleobase transport activity.|||Glycosylated.|||Highly expressed in heart, spleen, lung, liver and testis. Lower level of expression in brain and kidney (PubMed:11027664). Expressed in adipose tissues, brown adipocytes expressing significantly higher amounts than white adipocytes (PubMed:35790189). Expressed in seminiferous tubules (PubMed:23639800).|||Identified in a complex with STOM.|||Knockout mice show an increase in extracellular inosine levels and consequently enhancement differentiation and thermogenic capacity of brown adipocytes (PubMed:35790189). Knockout mice show an increased brown adipocyte tissue function and browning of white adipocyte tissue, and are resistant to diet-induced obesity (PubMed:35790189).|||Lateral cell membrane|||Membrane|||Transporter activity is sensitive to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR).|||Uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:11085929, PubMed:35790189). Functions as a Na(+)-independent transporter (By similarity). Involved in the transport of nucleosides such as adenosine, guanosine, inosine, uridine, thymidine and cytidine (PubMed:11085929, PubMed:35790189, PubMed:23639800). Also transports purine (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil) (By similarity). Mediates basolateral nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis-barrier (By similarity). Regulates inosine levels in brown adipocytes tissues (BAT) and extracellular inosine levels, which controls BAT-dependent energy expenditure (PubMed:35790189). http://togogenome.org/gene/10090:Hspa4l ^@ http://purl.uniprot.org/uniprot/P48722 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||By hyperosmolar salt stress and heat shock.|||Cytoplasm|||Highly expressed in testis. Also expressed in renal medulla of water-restricted animals.|||Homodimer.|||Nucleus|||Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. http://togogenome.org/gene/10090:Nck2 ^@ http://purl.uniprot.org/uniprot/O55033|||http://purl.uniprot.org/uniprot/Q8BQ28 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Interacts with DOCK1, LIMS1 and TGFB1I1. Part of a complex containing PPP1R15B, PP1 and NCK2. Interacts with FASLG. Interacts with AXL. Interacts with PAK1, PKN2 and SOS1. Interacts (via SH2 domain) with EGFR. Interacts (via SH2 domain) with DDR1 (By similarity). http://togogenome.org/gene/10090:Npepl1 ^@ http://purl.uniprot.org/uniprot/Q3UD03|||http://purl.uniprot.org/uniprot/Q6NSR8 ^@ Function|||Similarity ^@ Belongs to the peptidase M17 family.|||Probably catalyzes the removal of unsubstituted N-terminal amino acids from various peptides. http://togogenome.org/gene/10090:Kcnip1 ^@ http://purl.uniprot.org/uniprot/Q9JJ57 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the recoverin family.|||Cell membrane|||Component of heteromultimeric potassium channels (PubMed:19713751). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). Part of a heterooctamer composed of the tetrameric channel and four KCNIP1 chains (By similarity). Interacts with KCND3 and the N-terminal domain of KCND2. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. Self-associates to form homodimers and homotetramers. Interacts with KCNIP2 isoform 3 in a calcium-dependent manner (By similarity).|||Cytoplasm|||Expressed in brain. Found in a subpopulation of neurons widely distributed and enriched in Purkinje cells of the cerebellum and in the reticular thalamic and medial habenular nuclei.|||Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Regulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. Modulates KCND2/Kv4.2 currents (PubMed:14572458). In vitro, modulates KCND1/Kv4.1 currents (By similarity). Increases the presence of KCND2 at the cell surface.|||dendrite http://togogenome.org/gene/10090:Zfp28 ^@ http://purl.uniprot.org/uniprot/P10078 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed predominantly in ovary.|||Expression decreases in embryo after day 16.|||May be involved in transcriptional regulation. May have a role in embryonic development.|||Nucleus http://togogenome.org/gene/10090:Psme2 ^@ http://purl.uniprot.org/uniprot/G3X9V0|||http://purl.uniprot.org/uniprot/P97372|||http://purl.uniprot.org/uniprot/Q5SVP3 ^@ Function|||Induction|||Similarity|||Subunit ^@ Belongs to the PA28 family.|||By interferon gamma.|||Heterodimer of PSME1 and PSME2, which forms a hexameric ring.|||Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. http://togogenome.org/gene/10090:Rnf121 ^@ http://purl.uniprot.org/uniprot/Q8R1Z9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RNF121 family.|||E3 ubiquitin ligase which accepts ubiquitin and transfers it to substrates thereby promoting their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway which is a pathway involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (By similarity). May regulate the unfolded protein response to reduce endoplasmic reticulum stress (By similarity).|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Mettl9 ^@ http://purl.uniprot.org/uniprot/Q9EPL4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the METTL9 family.|||Endoplasmic reticulum|||Expressed in liver, colon, small intestine, skin, kidney and to a lesser extent in spleen, lung, thymus and stomach. Not detected in fibroblast and endothelial cells.|||Mitochondrion|||Protein-histidine N-methyltransferase that specifically catalyzes 1-methylhistidine (pros-methylhistidine) methylation of target proteins (PubMed:33563959, PubMed:34218407). Mediates methylation of proteins with a His-x-His (HxH) motif (where 'x' is preferably a small amino acid) (PubMed:33563959, PubMed:34218407). Catalyzes methylation of target proteins such as S100A9, NDUFB3, SLC39A5, SLC39A7, ARMC6 and DNAJB12; 1-methylhistidine modification may affect the binding of zinc and other metals to its target proteins (PubMed:33563959, PubMed:34218407). Constitutes the main methyltransferase for the 1-methylhistidine modification in cell (PubMed:33563959). http://togogenome.org/gene/10090:Efnb3 ^@ http://purl.uniprot.org/uniprot/O35393|||http://purl.uniprot.org/uniprot/Q543Q7 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. May play a pivotal role in forebrain function. Binds to, and induce the collapse of, commissural axons/growth cones in vitro. May play a role in constraining the orientation of longitudinally projecting axons.|||Expressed in the floor plate throughout the period of commissural axon pathfinding (PubMed:9484836, PubMed:10704386). In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912).|||Expressed on lateral floor plate cells, specifically on commissural axon segments that have passed through the floor plate. Expressed in cells of the retinal ganglion cell layer during retinal axon guidance to the optic disk (PubMed:9484836, PubMed:10704386). Expressed in myogenic progenitor cells (PubMed:27446912).|||Interacts with GRIP1 and GRIP2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Glyr1 ^@ http://purl.uniprot.org/uniprot/D3YYT1|||http://purl.uniprot.org/uniprot/Q922P9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HIBADH-related family. NP60 subfamily.|||Chromosome|||Cytokine-like nuclear factor with chromatin gene reader activity involved in chromatin modification and regulation of gene expression (PubMed:29759984). Acts as a nucleosome-destabilizing factor that is recruited to genes during transcriptional activation. Recognizes and binds histone H3 without a preference for specific epigenetic markers and also binds DNA. Interacts with KDM1B and promotes its histone demethylase activity by facilitating the capture of H3 tails, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes. Stimulates the acetylation of 'Lys-56' of nucleosomal histone H3 (H3K56ac) by EP300 (By similarity). With GATA4, co-binds a defined set of heart development genes and coregulates their expression during cardiomyocyte differentiation (PubMed:35182466). Regulates p38 MAP kinase activity by mediating stress activation of MAPK14/p38alpha and specifically regulating MAPK14 signaling. Indirectly promotes phosphorylation of MAPK14 and activation of ATF2. The phosphorylation of MAPK14 requires upstream activity of MAP2K4 and MAP2K6 (By similarity).|||Homotetramere. Interacts with MAPK14. Interacts with KDM1B at nucleosomes; this interaction stimulates H3K4me1 and H3K4me2 demethylation. Binds to mononucleosomes. Interacts with GATA4; the interaction is required for a synergistic activation of GATA4 target genes transcription.|||In the dehydrogenase domain, the conserved NAD(P)H-binding sites and sequence similarity to plant dehydrogenases suggest that this protein may have oxidoreductase activity. However, since the active site is not conserved, the dehydrogenase domain seems to serve as a catalytically inert oligomerization module.|||Nucleus|||The A.T hook DNA-binding domain is required for the interaction with MAPK14.|||The PWWP domain is a H3 reader and strongly binds DNA. http://togogenome.org/gene/10090:Nop2 ^@ http://purl.uniprot.org/uniprot/E9QN31 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.|||nucleolus http://togogenome.org/gene/10090:Tas2r130 ^@ http://purl.uniprot.org/uniprot/P59530 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in 15% taste bud cells in circumvallate and foliate papillae but only in 2% in fungiform papillae. Expressed in gastric and duodenal tissues.|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Vps72 ^@ http://purl.uniprot.org/uniprot/Q62481 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VPS72/YL1 family.|||Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41 and VPS72/YL1. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Also part of a multiprotein complex which contains SRCAP and which binds to H2AZ1/H2AZ. Interacts (via N-terminal domain) with H2AZ1; the interaction is enhanced by VPS72 phosphorylation which is promoted by ZNHIT1 (PubMed:30842416).|||Deposition-and-exchange histone chaperone specific for H2AZ1, specifically chaperones H2AZ1 and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP-dependent exchange of histone H2AZ1/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling.|||In all tissues examined, most abundantly in brain and thymus.|||Nucleus|||Phosphorylation is enhanced by ZNHIT1 and promotes the interaction of VPS72 with histone H2AZ1. http://togogenome.org/gene/10090:Mrps6 ^@ http://purl.uniprot.org/uniprot/P58064|||http://purl.uniprot.org/uniprot/Q3TLQ4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS6 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Cd160 ^@ http://purl.uniprot.org/uniprot/O88875 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in resting and activated NK cell subsets (at protein level) (PubMed:25711213, PubMed:16177084). Expressed in resting NKT cells (at protein level) (PubMed:16177084). Expressed in activated CD8+ T cells (at protein level). Highly expressed in intraepithelial lymphocyte (IEL) subsets, particularly in innate-like CD8A-positive IELs (at protein level) (PubMed:22801499).|||Homomultimer; disulfide-linked (By similarity). Interacts with classical and non-classical MHC class I molecules (PubMed:16177084). Interacts with TNFRSF14 (via cysteine-rich domain 1); this interaction is direct (PubMed:18193050). Interacts with LCK and CD247/CD3 zeta chain (By similarity).|||No visible phenotype.|||Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells (By similarity). Receptor for both classical and non-classical MHC class I molecules (PubMed:16177084). Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response (PubMed:25711213). On activated CD4+ T cells, interacts with TNFRSF14 and down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (By similarity). In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and pro-inflammatory cytokines (PubMed:22801499).|||Secreted|||The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions. http://togogenome.org/gene/10090:Cnga1 ^@ http://purl.uniprot.org/uniprot/P29974 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA1 subfamily.|||Cell membrane|||Forms a heterotetramer with CNGB1 in a 3:1 ratio. May also form cyclic nucleotide-activated homotetrameric channels, that are efficiently activated by saturating cGMP, but poorly activated by saturating cAMP compared to the heterotetramer with CNGB1.|||Rod cells in the retina and inner medulla of kidney.|||Subunit of the rod cyclic GMP-gated cation channel, which is involved in the final stage of the phototransduction pathway. When light hits rod photoreceptors, cGMP concentrations decrease causing rapid closure of CNGA1/CNGB1 channels and, therefore, hyperpolarization of the membrane potential.|||The C-terminal coiled-coil domain mediates homotrimerization of CNGA subunits. http://togogenome.org/gene/10090:Asb5 ^@ http://purl.uniprot.org/uniprot/Q2VPQ8|||http://purl.uniprot.org/uniprot/Q9D1A4 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. May play a role in the initiation of arteriogenesis (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Adgrl3 ^@ http://purl.uniprot.org/uniprot/D3Z3X6|||http://purl.uniprot.org/uniprot/D3Z634|||http://purl.uniprot.org/uniprot/D3Z6H9|||http://purl.uniprot.org/uniprot/Q80TS3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Cell junction|||Cell membrane|||Interacts (via olfactomedin-like domain) with FLRT3 (via extracellular domain); the interaction is direct(PubMed:22405201, PubMed:24739570, PubMed:26235031). Identified in a complex with FLRT3 and UNC5B; does not interact with UNC5B by itself. Identified in a complex with FLRT3 and UNC5D; does not interact with UNC5D by itself (By similarity). Interacts (via olfactomedin-like domain) with FLRT1 (via extracellular domain) (PubMed:22405201). Interacts (via olfactomedin-like domain) with FLRT2 (via extracellular domain) (PubMed:22405201, PubMed:25728924). Interacts (via extracellular domain) with TENM1 (PubMed:24739570). Interacts (via extracellular domain) with TENM3 (PubMed:22405201).|||Membrane|||Mutant mice are viable and present no obvious physical phenotype. Compared to wild-type, mutants are hyperactive, and their dorsal striatum contains higher levels of the neurotransmitters dopamine and serotonin. Cocaine treatment causes a higher increase in locomotor activity than in wild-type.|||O-glycosylated (major) and N-glycosylated.|||Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25728924, PubMed:26235031). Plays a role in the development of glutamatergic synapses in the cortex (PubMed:22405201, PubMed:24739570). Important in determining the connectivity rates between the principal neurons in the cortex (PubMed:24739570).|||Proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit.|||The Olfactomedin-like domain is required for the synapse-promoting function and the interaction with FLRT3. The Olfactomedin-like and the SUEL-type lectin domains are required for the interaction with TENM1.|||axon http://togogenome.org/gene/10090:Csrp1 ^@ http://purl.uniprot.org/uniprot/P97315 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Could play a role in neuronal development.|||Interacts with ASCC1; ASCC2 and TRIP4.|||Nucleus http://togogenome.org/gene/10090:Tnfaip1 ^@ http://purl.uniprot.org/uniprot/O70479 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BACURD family.|||Component of the BCR(TNFAIP1) E3 ubiquitin ligase complex, at least composed of CUL3, TNFAIP1/BACURD2 and RBX1. Interacts with RHOA; with a preference for RhoA-GDP. Interacts with RHOB. Interacts with PCNA. Interacts with CSNK2B (By similarity).|||Cytoplasm|||Endosome|||Nucleus|||Phosphorylation at Ser-280 by CK2 facilitates the nucleus localization and increases interaction with PCNA.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure. The BCR(TNFAIP1) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. Its interaction with RHOB may regulate apoptosis. May enhance the PCNA-dependent DNA polymerase delta activity (By similarity). http://togogenome.org/gene/10090:Mtrfr ^@ http://purl.uniprot.org/uniprot/Q80VP5 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prokaryotic/mitochondrial release factor family.|||In contrast to other members of the family, lacks the regions that come into close contact with the mRNA in the ribosomal A-site and determine the STOP codon specificity, suggesting a loss of codon specificity for translation release factor activity.|||Interacts (via C-terminus) with MTRES1 (via S4 domain). Associates with mitoribosomal S39 large subunit, peptidyl tRNA and nascent chain.|||Methylation of glutamine in the GGQ triplet by HEMK1.|||Mitochondrion|||Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation. As heterodimer with MTRES1, ejects the unfinished nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for MTRES1 and MTRF during mitoribosome rescue.|||The GGQ domain interacts with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis. http://togogenome.org/gene/10090:Smc6 ^@ http://purl.uniprot.org/uniprot/Q924W5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMC family. SMC6 subfamily.|||Chromosome|||Core component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components (By similarity).|||Forms a heterodimer with SMC5. Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. Interacts with NSMCE1. Interacts with NSMCE2. Interacts with SLF1. Interacts with SLF2. Interacts with RAD18. Interacts with SIMC1.|||Nucleus|||Nucleus speckle|||PML body|||Phosphorylated.|||Sumoylated by NSMCE2/MMS21.|||The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC5, forming a V-shaped heterodimer.|||Ubiquitinated.|||telomere http://togogenome.org/gene/10090:Ksr1 ^@ http://purl.uniprot.org/uniprot/Q61097 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the protein kinase superfamily, the ATP-binding motif VAIK has an arginine instead of a lysine residue suggesting that KSR1 cannot bind ATP and therefore lacks protein kinase activity. However, KSR1 is capable of binding ATP (PubMed:21441104). Has protein kinase activity towards MAP2K1 in presence of RAF1/c-RAF in vitro (PubMed:21441104).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in brain, spleen and testis. Isoform 1 is highly expressed spleen and weakly in testis, and isoform 2 is highly expressed in brain and weakly in testis.|||Homodimer (By similarity). Heterodimerizes (via N-terminus) with BRAF (via N-terminus) in a MAP2K1/MEK1 or MAP2K2/MEK2-dependent manner (By similarity). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (PubMed:10891492, PubMed:10409742, PubMed:21441104). Binding to MAP2K1/MEK1 releases the intramolecular inhibitory interaction between KSR1 N-terminus and kinase domains which is required for the subsequent RSK1 dimerization with BRAF (By similarity). Identified in a complex with AKAP13, MAP2K1 and BRAF (PubMed:21102438, PubMed:23250398). Interacts with AKAP13 and BRAF (PubMed:21102438). Interacts with RAF and MAPK/ERK, in a Ras-dependent manner (PubMed:10891492). Interacts with 14-3-3 proteins including YWHAB (PubMed:10409742, PubMed:11741534). Interacts with HSP90AA1/HSP90, YWHAE/14-3-3 and CDC37 (PubMed:10409742). The binding of 14-3-3 proteins to phosphorylated KSR1 prevents the membrane localization (PubMed:10409742). Interacts with MARK3/C-TAK1 (PubMed:11741534, PubMed:12941695). Interacts with PPP2R1A and PPP2CA (PubMed:12932319). Interacts with VRK2 (By similarity).|||Membrane|||Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (PubMed:10409742, PubMed:12932319, PubMed:21102438, PubMed:21441104). Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (By similarity). Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (PubMed:21102438). Its kinase activity is unsure (PubMed:21441104). Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (PubMed:21441104).|||Phosphorylated on Ser-297 and, to a higher extent, on Ser-392 by MARK3 (PubMed:11741534, PubMed:12941695). Dephosphorylated on Ser-392 by PPP2CA (PubMed:12932319). Phosphorylated KSR1 is cytoplasmic and dephosphorylated KSR1 is membrane-associated (Probable). Phosphorylated by PKA at Ser-838. Phosphorylation at Ser-838 is required for cAMP-dependent activation of MAPK1 and/or MAPK3 (PubMed:21102438).|||The N-terminal region mediates interaction with BRAF (PubMed:23250398). Also mediates membrane localization (PubMed:23250398).|||The protein kinase domain is predicted to be catalytically inactive. The domain is sufficient for KSR1 and KSR1-mediated MAP2K1 and MAP2K2 membrane localization. The domain is required but not sufficient for MAP kinase-mediated inhibition of ELK1 phosphorylation (PubMed:10409742).|||ruffle membrane http://togogenome.org/gene/10090:Slc25a25 ^@ http://purl.uniprot.org/uniprot/A2ASZ8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport.|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Electroneutral antiporter that most probably mediates the transport of adenyl nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it could have a broader specificity for adenyl nucleotides. By regulating the mitochondrial matrix adenyl nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenyl nucleotide-dependent metabolic pathways.|||Homozygous knockout mice lacking Slc25a25 are viable, born at the expected Mendelian ratio and fertile (PubMed:21296886). They display resistance to diet-induced obesity and reduced physical endurance (PubMed:21296886). Cellular metabolism is characterized by reduction in total mitochondrial and non-mitochondrial respiration, which leads to reduction in available ATP (PubMed:21296886).|||Linker region/H9 could directly block the transport of substrates across the transporter.|||Mitochondrion inner membrane|||The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity.|||The regulatory N-terminal domain/NTD, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity. http://togogenome.org/gene/10090:Zfp541 ^@ http://purl.uniprot.org/uniprot/Q0GGX2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Females exhibit normal fertility with no apparent defects in ovaries while males are infertile with a small testis and an absence of spermatids and spermatozoa (PubMed:33961623, PubMed:34075040, PubMed:35320728, PubMed:35341968). Spermatocytes fail to complete meiotic prophase (PubMed:34075040). An aberrant recruitment of DNA double-strand breaks (DSBs) machinery and generation of massive DSBs seen in spermatocytes after mid-pachytene (PubMed:35320728, PubMed:35341968).|||Germ-cell-specific. Specifically present in testicular spermatogenic cells, but not in testicular and mature sperm. During spermatogenesis, it is present in spermatocytes and round spermatids only (at protein level).|||Interacts with DNTTIP1 (PubMed:18849567). Identified in a complex with KCTD19, HDAC1 and HSPA2 (PubMed:18849567). Identified in a complex with HDAC1, HDAC2, DNTTIP1 and KCTD19 (PubMed:33961623, PubMed:35341968). Identified in a complex with KCTD19 and HDAC1 (PubMed:33961623).|||Nucleus|||Transcription regulator which is essential for male fertility and for the completion of meiotic prophase in spermatocytes (PubMed:18849567, PubMed:35341968, PubMed:34075040, PubMed:33961623, PubMed:35320728). Regulates progression of the pachytene stage of meiotic prophase by activating the expression of genes involved in meiosis and post-meiosis during spermatogenesis (PubMed:35341968). Maintains the repression of pre-pachytene transcriptional programs, including meiotic double-strand breaks (DSB) formation genes in pachytene spermatocytes and suppresses aberrant DSB formation after mid-pachytene, thus ensuring meiosis progression (PubMed:35320728). http://togogenome.org/gene/10090:Chchd5 ^@ http://purl.uniprot.org/uniprot/Q9CQP3 ^@ Subcellular Location Annotation|||Subunit ^@ Mitochondrion intermembrane space|||Monomer. http://togogenome.org/gene/10090:Cmtr2 ^@ http://purl.uniprot.org/uniprot/Q8BWQ4 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Nucleus|||S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the second nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) (cap0) to produce m(7)GpppRmpNm (cap2). Recognizes a guanosine cap on RNA independently of its N(7) methylation status. Display cap2 methylation on both cap0 and cap1. Displays a preference for cap1 RNAs. http://togogenome.org/gene/10090:Syt14 ^@ http://purl.uniprot.org/uniprot/A0A1L1SVE7|||http://purl.uniprot.org/uniprot/B7ZP31|||http://purl.uniprot.org/uniprot/Q7TN84|||http://purl.uniprot.org/uniprot/Q8BL96 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Expressed in heart and testis. Expressed in brain (especially in the cerebellum).|||Homodimer. Can also form heterodimers (By similarity).|||May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Is Ca(2+)-independent.|||Membrane http://togogenome.org/gene/10090:Vmn1r143 ^@ http://purl.uniprot.org/uniprot/E9PUW9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd3g ^@ http://purl.uniprot.org/uniprot/P11942|||http://purl.uniprot.org/uniprot/Q3U4Y3 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Membrane|||Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface. Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G (PubMed:25920998).|||Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8. Phosphorylated also by PKC; leading to the TCR complex down-regulation.|||The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta.|||The absence of CD3G results in a severe reduction in the level of the TCR-CD3 at the cell surface of thymocytes and peripheral T cells. The development of both the TCRalphabeta and TCRgammadelta lineages are affected by the absence of CD3G. http://togogenome.org/gene/10090:Nosip ^@ http://purl.uniprot.org/uniprot/Q9D6T0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although mutant embryos are present at the expected Mendelian rate at 18.5 dpc, they die shortly after birth with signs of respiratory distress and cyanosis, likely due to craniofacial malformations. Malformations in knockout mice range from ocular hypotelorism, narrow snout, laterally cleft lip, and cleft secondary palate to cyclopia and presence of proboscis or a single head-like protrusion devoid of facial features. In addition, the weight of knockout embryos is significantly reduced. In knockout animals, PP2A activity is increased in palatal and facial tissues as compared to wild-type, but not in lungs, which do not seem to be affected by the mutation.|||Belongs to the NOSIP family.|||Cytoplasm|||E3 ubiquitin-protein ligase that is essential for proper development of the forebrain, the eye and the face. Catalyzes monoubiquitination of serine/threonine-protein phosphatase 2A (PP2A) catalytic subunit PPP2CA/PPP2CB (PubMed:25546391). Negatively regulates nitric oxide production by inducing NOS1 and NOS3 translocation to actin cytoskeleton and inhibiting their enzymatic activity (By similarity).|||Interacts with NOS1 and NOS3 (By similarity). Interacts with PP2A holoenzyme, containing PPP2CA, PPP2CB, PPP2R1A and PPP2R2A subunits (PubMed:25546391).|||Nucleus|||The U-box-like region is a truncated U-box domain. It is unknown whether it is functional or not. http://togogenome.org/gene/10090:Ap2a1 ^@ http://purl.uniprot.org/uniprot/P17426 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with HIP1 and RAB11FIP2 (By similarity). Interacts with SLC12A5 (PubMed:18625303). Interacts with clathrin (PubMed:7559550). Interacts with SGIP1 (PubMed:17626015). Interacts with RFTN1 (By similarity). Interacts with KIAA1107 (PubMed:29262337). Interacts with PICALM (By similarity). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts with ABCB11; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (By similarity). Probably interacts with ACE2 (via endocytic sorting signal motif); the interaction is inhibited by ACE2 phosphorylation (By similarity).|||Belongs to the adaptor complexes large subunit family.|||Cell membrane|||Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).|||Expressed in the brain (at protein level) (PubMed:23676497). Isoform A: Expressed only in neuronal tissue and skeletal muscle. Isoform B: Widely expressed.|||coated pit http://togogenome.org/gene/10090:Wee2 ^@ http://purl.uniprot.org/uniprot/Q66JT0 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.|||Cytoplasm|||Detected only in the oocytes at all developmental stages of the follicle including primary, secondary, preantral, and antral follicles with an increase in signal during development. Readily detectable at the mature oocyte, but disappears at 2.5 dpc. Detected in germinal vesicle (GV) and metaphase II-stage oocyte (at protein level).|||Nucleus|||Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1 and acts as a key regulator of meiosis during both prophase I and metaphase II. Required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, by phosphorylating CDK1 at 'Tyr-15', leading to inhibit CDK1 activity and prevent meiotic reentry. Also required for metaphase II exit during egg activation by phosphorylating CDK1 at 'Tyr-15', to ensure exit from meiosis in oocytes and promote pronuclear formation.|||Ovary-specific.|||Phosphorylated by PKA at Ser-15 in vitro, leading to activate kinase activity. Phosphorylation at Ser-15 by CaMK2, leading to increase its activity and promote metaphase II exit during egg activation. http://togogenome.org/gene/10090:Catsper4 ^@ http://purl.uniprot.org/uniprot/Q8BVN3 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:21224844, PubMed:17227845). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (Probable).|||Detected in hte testis during postnatal development at day 15. Restricted to the late-stage germline cells that line the seminiferous tubules.|||In contrast to the human ortholog, not activated by progesterone.|||Mice are normal but males are sterile. Male sterility is due to defects in sperm motility unability to fertilize intact eggs.|||Testis-specific.|||Voltage-gated calcium channel that plays a central role in sperm cell hyperactivation. Controls calcium entry to mediate the hyperactivated motility, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Activated by intracellular alkalinization.|||flagellum membrane http://togogenome.org/gene/10090:Mettl21a ^@ http://purl.uniprot.org/uniprot/Q9CQL0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METTL21 family.|||Cytoplasm|||Interacts with heat shock 70 family members; at least some of these proteins are methylation substrates.|||Protein-lysine methyltransferase that selectively trimethylates residues in heat shock protein 70 (HSP70) family members. Contributes to the in vivo trimethylation of Lys residues in HSPA1 and HSPA8. In vitro methylates 'Lys-561' in HSPA1, 'Lys-564' in HSPA2, 'Lys-585' in HSPA5, 'Lys-563' in HSPA6 and 'Lys-561' in HSPA8. http://togogenome.org/gene/10090:Alpk3 ^@ http://purl.uniprot.org/uniprot/Q924C5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.|||Expressed in the heart and skeletal muscle of adult mice.|||First detected in the cardiac crescent at 7.5 dpc when the developing heart became visible and remains through to 10.5 dpc.|||Involved in cardiomyocyte differentiation.|||Mice are viable and were born at the expected Mendelian ratio. They however develop spontaneous cardiomyopathy with features of both hypertrophic and dilated forms of cardiomyopathy. Cardiac hypertrophy is characterized by increased thickness of both left and right ventricular walls and by significantly increased heart weight. Some features are also associated with dilated cardiomyopathy. Cardiomyocytes show an altered architecture, characterized by reduced numbers of abnormal intercalated disks.|||Nucleus http://togogenome.org/gene/10090:Depp1 ^@ http://purl.uniprot.org/uniprot/Q8K2F3 ^@ Function|||Induction|||Subcellular Location Annotation ^@ Acts as a critical modulator of FOXO3-induced autophagy via increased cellular ROS.|||Cytoplasm|||Mitochondrion|||Peroxisome|||Up-regulated by hypoxia. http://togogenome.org/gene/10090:Lix1 ^@ http://purl.uniprot.org/uniprot/A0A158RFU7|||http://purl.uniprot.org/uniprot/Q3TSN5|||http://purl.uniprot.org/uniprot/Q6P566 ^@ Similarity ^@ Belongs to the LIX1 family. http://togogenome.org/gene/10090:Crxos ^@ http://purl.uniprot.org/uniprot/B6ZND8|||http://purl.uniprot.org/uniprot/B6ZND9|||http://purl.uniprot.org/uniprot/Q3UL53 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Hexb ^@ http://purl.uniprot.org/uniprot/P20060|||http://purl.uniprot.org/uniprot/Q3TXR9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Addition of GM2A stimulates the hydrolysis of sulfated glycosphingolipid SM2 and the ganglioside GM2.|||Belongs to the glycosyl hydrolase 20 family.|||Cortical granule|||Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides. The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide. Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A. During fertilization is responsible, at least in part, for the zona block to polyspermy. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and inactivates the sperm galactosyltransferase-binding site, accounting for the block in sperm binding to the zona pellucida (PubMed:8253842).|||Lysosome|||There are 3 forms of beta-hexosaminidase: hexosaminidase A is an heterodimer composed of one subunit alpha and one subunit beta (chain A and B); hexosaminidase B is an homodimer of two beta subunits (two chains A and B); hexosaminidase S is a homodimer of two alpha subunits (By similarity). The composition of the dimer (isozyme A versus isozyme S) has a significant effect on the substrate specificity of the alpha subunit active site (By similarity). http://togogenome.org/gene/10090:Spaar ^@ http://purl.uniprot.org/uniprot/A0A1B0GSZ0 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated in skeletal muscle upon acute injury.|||Expressed in the skeletal muscle.|||Interacts with components of the lysosomal V-ATPase complex (By similarity). Interacts with ATP6V0A1 (PubMed:28024296). Interacts with ATP6V0A2 (By similarity).|||Late endosome membrane|||Lysosome membrane|||Negative regulator of amino acid sensing and mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels and amino acids (By similarity). Negatively regulates mTORC1 activation by inhibiting recruitment of mTORC1 to lysosomes upon stimulation with amino acids: acts by promoting the formation of a tightly bound supercomplex composed of the lysosomal V-ATPase, Ragulator and Rag GTPases, preventing recruitment of mTORC1 (By similarity). Acts as a regulator of muscle regeneration following injury by regulating mTORC1 activation (PubMed:28024296).|||No visible phenotype. Mice were born at expected Mendelian ratio with no gross abnormalities. http://togogenome.org/gene/10090:Vmn1r93 ^@ http://purl.uniprot.org/uniprot/K7N6B8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hint1 ^@ http://purl.uniprot.org/uniprot/P70349 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HINT family.|||Cytoplasm|||Desumoylase activity is inhibited by zinc ions, and inhibition is released by nitric oxide or calcium-activated calmodulin.|||Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By similarity). Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (By similarity). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester (By similarity). Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide (By similarity). In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1 (By similarity). Modulates p53/TP53 levels and p53/TP53-mediated apoptosis. Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By similarity). Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RANGAP1 and RGS17 (PubMed:31088288).|||Homodimer (By similarity). Interacts with CDK7 (By similarity). Interacts with RUVBL1 and RUVBL2 and is associated with the LEF1/TCF1-CTNNB1 complex and with a KAT5 histone acetyltransferase complex (By similarity). Identified in a complex with MITF and CTNNB1 (By similarity). Interacts with CDC34 and RBX1, and is part of a SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By similarity). Interacts with SUMO1, SUMO2 and RGS17 (PubMed:31088288). Interacts with the Ten-1 ICD form of TENM1 (PubMed:31088288). Interacts with CALM1; interaction increases in the presence of calcium ions (PubMed:31088288).|||No visible phenotype. Mice display increased susceptibility to carcinogens.|||Nucleus|||Was originally thought to be a protein kinase C inhibitor and to bind zinc in solution. Both seem to be incorrect. http://togogenome.org/gene/10090:Dnlz ^@ http://purl.uniprot.org/uniprot/Q9D113 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation.|||Mitochondrion|||Oligomerizes in a concentration-dependent fashion. Interacts with HSPA9 (By similarity). http://togogenome.org/gene/10090:Cyp2j8 ^@ http://purl.uniprot.org/uniprot/G3UZ38 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Akr1b7 ^@ http://purl.uniprot.org/uniprot/P21300|||http://purl.uniprot.org/uniprot/Q5M9J9 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldo/keto reductase family.|||Castration resulted in a marked decrease in the level of the mRNA coding for the protein, whereas administration of testosterone to castrated males resulted in a marked increase.|||Cytoplasm|||Expressed exclusively in the epithelial cells of the deferent duct.|||Monomer.|||Reduces a broad range of aliphatic and aromatic aldehydes to the corresponding alcohols. Reduces prostaglandins (PubMed:19010934). May play a role in the metabolism of xenobiotic aromatic aldehydes (By similarity). http://togogenome.org/gene/10090:Il22ra2 ^@ http://purl.uniprot.org/uniprot/Q80XF5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type II cytokine receptor family.|||Highly expressed in lymph nodes and at lower levels in lung, spleen, and thymus. Not expressed in kidney, liver and heart.|||Receptor for IL22. Binds to IL22, prevents interaction with the functional IL-22R complex and blocks the activity of IL22 (in vitro). May play an important role as an IL22 antagonist in the regulation of inflammatory responses.|||Secreted http://togogenome.org/gene/10090:Myo19 ^@ http://purl.uniprot.org/uniprot/Q5SV80 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actin-based motor molecule with ATPase activity that localizes to the mitochondrion outer membrane (PubMed:24825904). Motor protein that moves towards the plus-end of actin filaments (PubMed:24825904). Required for mitochondrial inheritance during mitosis (By similarity). May be involved in mitochondrial transport or positioning (By similarity).|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Mitochondrion outer membrane|||Myosin is a hexamer of 2 heavy chains and 4 light chains: interacts with myosin light chains MYL9 and MYL12B.|||The MyMOMA (MYO19-specific mitochondrial outer membrane-association) region mediates association with the mitochondrion outer membrane via electrostatic interaction.|||cytoskeleton http://togogenome.org/gene/10090:Mtarc2 ^@ http://purl.uniprot.org/uniprot/Q922Q1 ^@ Cofactor|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Catalyzes the reduction of N-oxygenated molecules, acting as a counterpart of cytochrome P450 and flavin-containing monooxygenases in metabolic cycles. As a component of prodrug-converting system, reduces a multitude of N-hydroxylated prodrugs particularly amidoximes, leading to increased drug bioavailability. May be involved in mitochondrial N(omega)-hydroxy-L-arginine (NOHA) reduction, regulating endogenous nitric oxide levels and biosynthesis. Postulated to cleave the N-OH bond of N-hydroxylated substrates in concert with electron transfer from NADH to cytochrome b5 reductase then to cytochrome b5, the ultimate electron donor that primes the active site for substrate reduction.|||Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MTARC2.|||Mitochondrion outer membrane|||Peroxisome|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Klhl21 ^@ http://purl.uniprot.org/uniprot/Q3U410 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for efficient chromosome alignment and cytokinesis. The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome (By similarity).|||spindle http://togogenome.org/gene/10090:Cggbp1 ^@ http://purl.uniprot.org/uniprot/Q8BHG9 ^@ Function|||Miscellaneous|||Subcellular Location Annotation ^@ Binding is severely inhibited by complete or partial cytosine-specific DNA methylation of the binding motif.|||Binds to nonmethylated 5'-d(CGG)(n)-3' trinucleotide repeats in the FMR1 promoter. May play a role in regulating FMR1 promoter (By similarity).|||Nucleus http://togogenome.org/gene/10090:Sgsm1 ^@ http://purl.uniprot.org/uniprot/B2RQR5|||http://purl.uniprot.org/uniprot/Q8BPQ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RUTBC family.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Expressed only in brain.|||Interacts with RAB9A (GTP-bound form) and RAB9B (PubMed:25220469). Interacts with RAB3A, RAB4A, RAB5A, RAB8A, RAB11A, RAP1A, RAP1B, RAP2A and RAP2B. No interaction with RAB27A (By similarity).|||Interacts with numerous Rab family members, functioning as Rab effector for some, and as GTPase activator for others. Promotes GTP hydrolysis by RAB34 and RAB36. Probably functions as GTPase effector with RAB9A and RAB9B; does not stimulate GTP hydrolysis with RAB9A and RAB9B.|||trans-Golgi network http://togogenome.org/gene/10090:Apoc1 ^@ http://purl.uniprot.org/uniprot/P34928 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adult and fetal liver.|||Belongs to the apolipoprotein C1 family.|||Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein (By similarity). Binds free fatty acids and reduces their intracellular esterification.|||Secreted http://togogenome.org/gene/10090:Dync1li1 ^@ http://purl.uniprot.org/uniprot/Q3TWG5|||http://purl.uniprot.org/uniprot/Q8R1Q8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.|||Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. Probably involved in the microtubule-dependent transport of pericentrin. Is required for progress through the spindle assembly checkpoint. The phosphorylated form appears to be involved in the selective removal of MAD1L1 and MAD1L2 but not BUB1B from kinetochores (By similarity). Forms a functional Rab11/RAB11FIP3/dynein complex onto endosomal membrane that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (By similarity).|||Belongs to the dynein light intermediate chain family.|||Cytoplasm|||Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Self-associates. Interacts with DYNC1H1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with PCNT (By similarity). Forms a complex with RAB11FIP3 and RAB11A1; the interaction between DYNC1LI1 and RAB11FIP3 is direct and induces DYNC1LI1 localization onto endosomal membrane; the complex regulates endocytic trafficking (By similarity).|||Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs).|||Phosphorylated during mitosis but not in interphase.|||Recycling endosome membrane|||cytoskeleton|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Bglap2 ^@ http://purl.uniprot.org/uniprot/P86547 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the osteocalcin/matrix Gla protein family.|||Bone.|||Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX (By similarity). These residues are essential for the binding of calcium (By similarity). Carboxylated in a Ptprv/Esp-dependent process (PubMed:17693256, PubMed:20655470, PubMed:20655471). Decarboxylation promotes the hormone activity (PubMed:17693256, PubMed:20655470, PubMed:20655471, PubMed:21333348, PubMed:24074871).|||Mice lacking Bglap and Bglap2 show increased bone formation, characterized by higher bone mass and bones of improved functional quality (PubMed:8684484). Mice lacking Bglap and Bglap2 also display reduced male fertility due to decreased testosterone production in the testes (PubMed:21333348). Mice lacking Bglap and Bglap2 are passive and show greater anxiety-like behaviors due to impaired synthesis of neurotransmitters (PubMed:24074871).|||Secreted|||The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein: it acts as a negative regulator of bone formation and is required to limit bone formation without impairing bone resorption or mineralization (PubMed:8684484). The carboxylated form binds strongly to apatite and calcium (PubMed:17693256).|||The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development (PubMed:17693256, PubMed:20655470, PubMed:20655471, PubMed:21333348, PubMed:24074871). Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure (PubMed:17693256, PubMed:20655470, PubMed:20655471). Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner (PubMed:21333348). Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA) (PubMed:24074871, PubMed:28851741). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development (PubMed:24074871). http://togogenome.org/gene/10090:Ephb4 ^@ http://purl.uniprot.org/uniprot/P54761|||http://purl.uniprot.org/uniprot/Q3V1K8|||http://purl.uniprot.org/uniprot/Q8C7S3|||http://purl.uniprot.org/uniprot/Q8C8K1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Embryo display cardiovascular defects and lethality with very high penetrance. Growth retardation is observed at 9.5 dpc with arrested heart development and lack of blood flow. By 10.5 dpc degeneration and necrosis are apparent throughout the embryo. Conditional lymphovenous valves knockouts show a complete loss of lymphatic valves (PubMed:27400125).|||Expressed in various organ systems, including lung, liver, kidney, intestine, muscle and heart (PubMed:7478528). Expressed in myogenic progenitor cells (PubMed:27446912).|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts with RASA1; the interaction depends on EPHB4 tyrosine-phosphorylation (By similarity).|||Membrane|||Phosphorylated; autophosphorylation is stimulated by EFNB2.|||Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells.|||Specifically expressed in the developing cardiovascular system with higher expression in veins. First detected in the developing anterior cardinal vein at 8.75 dpc. Abundant expression at 16.5 dpc in various organ systems, including thymus, heart, lung and kidney, where it is associated with cells of endothelial origin. In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912). http://togogenome.org/gene/10090:C330018D20Rik ^@ http://purl.uniprot.org/uniprot/Q9CWB7 ^@ Similarity ^@ Belongs to the glutaredoxin family. YDR286C subfamily. http://togogenome.org/gene/10090:Ccdc6 ^@ http://purl.uniprot.org/uniprot/D3YZP9 ^@ Domain|||Subcellular Location Annotation ^@ Cytoplasm|||The protein has mostly an alpha helical conformation similar to myosin heavy-chain tail that might adopt a coiled-coil conformation.|||cytoskeleton http://togogenome.org/gene/10090:Vmn1r169 ^@ http://purl.uniprot.org/uniprot/L7N275 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Pdcd2 ^@ http://purl.uniprot.org/uniprot/P46718 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation ^@ Expressed during apoptosis of lymphoid and myeloid cells.|||May be a DNA-binding protein with a regulatory function. May play an important role in cell death and/or in regulation of cell proliferation.|||Nucleus|||Ubiquitinated by PRKN, promoting proteasomal degradation. http://togogenome.org/gene/10090:Exosc8 ^@ http://purl.uniprot.org/uniprot/Q9D753 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase PH family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC8 binds to ARE-containing RNAs (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Nanp ^@ http://purl.uniprot.org/uniprot/Q9CPT3 ^@ Activity Regulation|||Similarity ^@ Belongs to the HAD-like hydrolase superfamily. NANP family.|||Inhibited by vanadate and calcium. http://togogenome.org/gene/10090:Cphx1 ^@ http://purl.uniprot.org/uniprot/Q8BX39 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sall3 ^@ http://purl.uniprot.org/uniprot/Q62255 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sal C2H2-type zinc-finger protein family.|||During embryogenesis detected from 7 dpc onward in tissues derived from mesoderm and ectoderm.|||In adult brain, testis and kidney. In lower levels also in adult ovaries and embryonic stem cells. In embryo in developing neuroectoderm of brain, inner ear and spinal chord. Also weakly and transiently expressed in embryonic branchial arches, notochord, limb buds and heart.|||Lacks two zinc finger domains (6 and 7) and is the major isoform.|||Nucleus|||Probable transcription factor. http://togogenome.org/gene/10090:Or52m2 ^@ http://purl.uniprot.org/uniprot/Q7TRS6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrig3 ^@ http://purl.uniprot.org/uniprot/Q6P1C6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasmic vesicle membrane|||Detected in the lateral wall of the otic vesicle at 10.5 dpc. Enriched in lateral pouch epithelium at 12.5 dpc.|||Interacts with EGFR, ERBB2 and ERBB4 (in vitro).|||Mice display circling and head tossing behavior, due to a defect in inner ear morphogenesis. In mutants, fusion of the canal pouches starts earlier than normal and involves an abnormally large region, leading to truncation of the lateral semicircular canal in the inner ear. Nevertheless, hearing seems to be normal. Mutant mice also display craniofacial deformities, and especially a dramatically shortened snout.|||Plays a role in craniofacial and inner ear morphogenesis during embryonic development. Acts within the otic vesicle epithelium to control formation of the lateral semicircular canal in the inner ear, possibly by restricting the expression of NTN1.|||Widely expressed. http://togogenome.org/gene/10090:H2ac4 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Vmn1r193 ^@ http://purl.uniprot.org/uniprot/Q8R258 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pi4k2b ^@ http://purl.uniprot.org/uniprot/Q8CBQ5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PI3/PI4-kinase family. Type II PI4K subfamily.|||Cell membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Together with PI4K2A and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells and is likely to be involved in the regulation of vesicular trafficking.|||cytosol http://togogenome.org/gene/10090:Or52e5 ^@ http://purl.uniprot.org/uniprot/Q8VG26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Glt28d2 ^@ http://purl.uniprot.org/uniprot/Q8BML3 ^@ Similarity ^@ Belongs to the glycosyltransferase 28 family. http://togogenome.org/gene/10090:Hdac7 ^@ http://purl.uniprot.org/uniprot/E9PX62|||http://purl.uniprot.org/uniprot/E9PXW1|||http://purl.uniprot.org/uniprot/E9PXW8|||http://purl.uniprot.org/uniprot/Q8C2B3 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the histone deacetylase family. HD type 2 subfamily.|||Cytoplasm|||Highly expressed in heart and lung. Expressed at intermediate level in muscle.|||Interacts with KDM5B (By similarity). Interacts with KAT5 and EDNRA. Interacts with HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, NCOR1, NCOR2, SIN3A, SIN3B, RBBP4, RBBP7, MTA1L1, SAP30 and MBD3. Interacts with the 14-3-3 protein YWHAE, MEF2A, MEF2B and MEF2C. Interacts with ZMYND15. Interacts with PML (By similarity). Interacts with FOXP3. Interacts with RARA (By similarity).|||Its activity is inhibited by Trichostatin A (TSA), a known histone deacetylase inhibitor.|||May be phosphorylated by CaMK1. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Phosphorylation at Ser-178 by MARK2, MARK3 and PRKD1 promotes interaction with 14-3-3 proteins and export from the nucleus. Phosphorylation at Ser-178 is a prerequisite for phosphorylation at Ser-204 (By similarity).|||Nucleus|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events.|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Positively regulates the transcriptional repressor activity of FOXP3 (By similarity). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (By similarity). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (By similarity).|||The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm. http://togogenome.org/gene/10090:Smim11 ^@ http://purl.uniprot.org/uniprot/Q99J19 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in brain, heart, kidney, thymus, liver, stomach, muscle, lung, testis, ovary, skin and eye.|||Membrane http://togogenome.org/gene/10090:Gpr160 ^@ http://purl.uniprot.org/uniprot/Q3U3F9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Ppp1r37 ^@ http://purl.uniprot.org/uniprot/Q8BKR5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PPP1R37 family.|||Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.|||Interacts with PPP1CA. http://togogenome.org/gene/10090:Ift27 ^@ http://purl.uniprot.org/uniprot/Q9D0P8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:19253336). Interacts with IFT25 (PubMed:28430876). Interacts with IFT70B (PubMed:23810713). Interacts with RABL2/RABL2A; binding is equal in the presence of GTP or GDP (PubMed:23055941). Interacts with IFT88 (PubMed:19253336). Interacts with ARL6; recognizes and binds with the GTP-free form of ARL6 (By similarity).|||Cytoplasm|||Expressed predominantly in the testis (at protein level) (PubMed:28964737). Co-localizes with RABL2/RABL2A in the midpiece of elongated spermatids within the testis (at protein level).|||Null mutants retain the ability to ciliate and survive through gestation. They die shortly after birth due to different phenotypes reminiscent of Shh signaling defects: polydactyly, lung isomerisms, and structural heart defects (PubMed:25446516). Conditional knockout in male germ cells results in infertility, abnormal sperm morphology, significantly reduced sperm count and sperm mobility (PubMed:28964737). Mutant mice with germline deletion of IFT27 die shortly after birth with structural defects in most organs including the kidneys, where duplicated collecting duct system and/or duplex kidney is often observed. Conditional deletion in the collecting duct results in smaller kidneys that develop only mild tubule dilation with age whereas conditional deletion from the peri-Wolffian duct stroma results in duplex kidneys (PubMed:29626631).|||Small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6 (PubMed:25446516). Not involved in entry of the BBSome complex into cilium. Prevents aggregation of GTP-free ARL6. Required for hedgehog signaling (PubMed:25446516). Forms a subcomplex within the IFT complex B with IFT25 (By similarity). Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation (PubMed:28964737). Plays a role in the early development of the kidney (PubMed:29626631). May be involved in the regulation of ureteric bud initiation (PubMed:29626631).|||cilium|||flagellum http://togogenome.org/gene/10090:Yap1 ^@ http://purl.uniprot.org/uniprot/P46938 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YAP1 family.|||Binds to the SH3 domain of the YES kinase (By similarity). Binds to WBP1 and WBP2 (PubMed:7644498). Binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif (PubMed:9407065). The phosphorylated form interacts with YWHAB (By similarity). Interacts (via WW domains) with LATS1 (via PPxY motif 2) (By similarity). Interacts with LATS2 (By similarity). Interacts (via WW domain 1) with isoform JM-A of ERBB4 (via PPxY motif 2) (By similarity). Interacts with TEAD1, TEAD2 and TEAD3 (By similarity). Interacts with TP73 and HCK (By similarity). Interacts with RUNX1 (By similarity). Interacts with TEAD4 (PubMed:20123908). Interacts (via WW domains) with PTPN14 (via PPxY motif 2); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional co-activator activity (By similarity). Interacts (when phosphorylated at Ser-112) with SMAD2, SMAD3 and WWTR1 (PubMed:21145499). Interacts with PRRG2 (via cytoplasmic domain) (By similarity). Interacts (via WW domains) with PRRG4 (via cytoplasmic domain) (By similarity). Interacts (phosphorylated) with CLDN18; the interaction sequesters YAP1 away from the nucleus and thereby restricts transcription of YAP1 target genes (PubMed:29400695). Interacts with SMAD1 (By similarity).|||Cell junction|||Cytoplasm|||Isoforms lacking the transactivation domain seen in striatal neurons (at protein level). Ubiquitous. Isoform 2 is expressed at higher levels in the neural tissues. In the embryo, it is expressed in brain, eye, and the maxillary and frontonasal components of the primary palate.|||Nucleus|||Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation. Phosphorylated by ABL1; leading to YAP1 stabilization, enhanced interaction with TP73 and recruitment onto proapoptotic genes; in response to DNA damage. Phosphorylation at Ser-385 and Ser-388 by CK1 is triggered by previous phosphorylation at Ser-382 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation (By similarity). Phosphorylated at Thr-104, Ser-123, Ser-352 and Thr-397 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regulation of apoptosis by YAP1 (By similarity).|||The first coiled-coil region mediates most of the interaction with TEAD transcription factors.|||Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:29400695). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization. Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (By similarity). In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:21145499).|||Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase. http://togogenome.org/gene/10090:Phb ^@ http://purl.uniprot.org/uniprot/P67778 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) In neuronal cells, cell surface-expressed PHB1 is involved in human enterovirus 71/EV-71 entry into neuronal cells specifically, while membrane-bound mitochondrial PHB1 associates with the virus replication complex and facilitates viral replication (PubMed:29324904). May serve as a receptor for EV71 (PubMed:29324904).|||(Microbial infection) Interacts with human enterovirus 71/EV-71 capsid protein VP0, protein 3CD and protease 3C.|||Belongs to the prohibitin family.|||Cell membrane|||Cytoplasm|||In B cells, expression is increased by CD40 engagement (at protein level).|||In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (PubMed:24856930). Regulates mitochondrial respiration activity playing a role in cellular aging (PubMed:11302691). The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:31819158). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (By similarity).|||In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses (By similarity). Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells (By similarity).|||In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates (PubMed:23241883). Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (PubMed:23241883).|||Interacts with PHB2. Interacts with STOML2. Interacts with CD86 (via cytoplasmic domain); the interactions increases after priming with CD40 (PubMed:23241883).|||Mitochondrion inner membrane|||Nucleus|||Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus (PubMed:11302691, PubMed:20959514, PubMed:23241883, PubMed:24856930, PubMed:29324904). Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner (PubMed:24947361). Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells (By similarity).|||Target of the anti-cancer drug Rocaglamide (Roc-A).|||Throughout gestation, highly expressed in brown fat, heart, liver, developing renal tubules and neurons, and detected at lower levels in tissues such as lung and exocrine pancreas.|||Widely expressed in different tissues. http://togogenome.org/gene/10090:Ralyl ^@ http://purl.uniprot.org/uniprot/Q8BTF8 ^@ Similarity ^@ Belongs to the RRM HNRPC family. RALY subfamily. http://togogenome.org/gene/10090:Churc1 ^@ http://purl.uniprot.org/uniprot/Q6DG52 ^@ Function|||Similarity ^@ Belongs to the Churchill family.|||Transcriptional activator that mediates FGF signaling during neural development (By similarity). Plays a role in the regulation of cell movement (By similarity). Does not bind DNA by itself (By similarity). http://togogenome.org/gene/10090:Tor1a ^@ http://purl.uniprot.org/uniprot/Q3TV62|||http://purl.uniprot.org/uniprot/Q9ER39 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals fail to feed or vocalize and die within 48 hours of birth. At 18 dpc, the global structure of the central nervous system is normal. However, at the cellular level, nuclear envelope abnormalities, with membranous vesicle-appearing structures in the perinuclear space, are observed in multiple areas of the central nervous system, including neurons of the spinal cord, pons, frontal cortex, and hippocampus.|||At 16 dpc and 18 dpc, widely expressed with higher expression levels in neural tissues. In the spinal cord, expressed as early as 12 dpc until P21, the expression levels decrease in the adulthood (at protein level).|||Belongs to the ClpA/ClpB family. Torsin subfamily.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum lumen|||Homohexamer. Interacts with TOR1B; the interaction may be specific of neural tissues. Interacts (ATP-bound) with TOR1AIP1 and TOR1AIP2; the interactions induce ATPase activity. Interacts with KLHL14; preferentially when ATP-free. Interacts with KLC1 (via TPR repeats); the interaction associates TOR1A with the kinesin oligomeric complex. Interacts with COPS4; the interaction associates TOR1A with the CSN complex. Interacts with SNAPIN; the interaction is direct and associates SNAPIN with the CSN complex. Interacts with STON2. Interacts (ATP-bound) with SYNE3 (via KASH domain); the interaction is required for SYNE3 nuclear envelope localization. Interacts with VIM; the interaction associates TOR1A with the cytoskeleton. Interacts with PLEC. Interacts (ATP-bound) with SLC6A3; regulates SLC6A3 transport to the plasma membrane.|||N-glycosylated.|||Nucleus membrane|||Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular trafficking and may regulate the subcellular location of multipass membrane proteins such as the dopamine transporter SLC6A3, leading to the modulation of dopamine neurotransmission. In the endoplasmic reticulum, plays a role in the quality control of protein folding by increasing clearance of misfolded proteins such as SGCE variants or holding them in an intermediate state for proper refolding. May have a redundant function with TOR1B in non-neural tissues.|||Widely expressed (at protein level).|||cytoskeleton|||growth cone|||secretory vesicle|||synaptic vesicle|||synaptosome http://togogenome.org/gene/10090:Tdpoz2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YVW8 ^@ Similarity ^@ Belongs to the Tdpoz family. http://togogenome.org/gene/10090:Cfap161 ^@ http://purl.uniprot.org/uniprot/Q6P8Y0 ^@ Function|||Subcellular Location Annotation ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Fam120b ^@ http://purl.uniprot.org/uniprot/Q6RI63 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the constitutive coactivator of PPAR-gamma family.|||Expressed throughout the embryonic developmental stages from 5 dpc to 19 dpc (at protein level).|||Functions as a transactivator of PPARG and ESR1. Functions in adipogenesis through PPARG activation.|||Interacts with ESR1 and RXRA. Interacts with PPARG; in a ligand-independent manner.|||Nucleus|||Ubiquitously expressed (at protein level).|||Up-regulated in differentiating adipocytes (at protein level). http://togogenome.org/gene/10090:Fam110d ^@ http://purl.uniprot.org/uniprot/Q80X91 ^@ Similarity ^@ Belongs to the FAM110 family. http://togogenome.org/gene/10090:Dst ^@ http://purl.uniprot.org/uniprot/Q91ZU6|||http://purl.uniprot.org/uniprot/S4R1P5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plakin or cytolinker family.|||Cell membrane|||Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1.|||Endoplasmic reticulum membrane|||H zone|||Homodimer. Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends. Isoform 2 interacts (via N-terminus) with ACTN2. Isoform 2 interacts (via N-terminus) with PLEC (via N-terminus). Isoform 5 interacts (via N-terminus) with COL17A1 (via cytoplasmic region). Isoform 5 interacts (via N-terminus) with ITGB4 isoform beta-4a (via cytoplasmic region). Isoform 5 interacts (via N-terminus) with ERBIN (via C-terminus). Isoform 5 associates (via C-terminal) with KRT5-KRT14 (via rod region) intermediate filaments of keratins (By similarity). Isoform 2 and isoform 6 can homodimerize (via N-terminus). Isoform 2 interacts (via N-terminus) with PLEC (via N-terminus). Interacts with the neuronal intermediate filament protein, PRPH. Interacts with DES. Interacts with SYNE3. Isoform 1 interacts with TMEM108 (PubMed:17287360).|||Incomplete sequence. Probably myristoylated on Gly-2. Probably S-palmitoylated on Cys-5 and Cys-7. Mutagenesis of Gly-2 to Ala inhibits cortical localization. Mutagenesis of Cys-5 to Ser inhibits cortical localization. Mutagenesis of Cys-7 to Ser inhibits cortical localization.|||Incomplete sequence. Transmembrane protein (helical transmembrane domain from amino acid 18 to 38).|||Isoform 1 and 2 are expressed in striated and heart muscle cells. Isoform 5 is expressed in the skin. Isoform 6 is expressed in sensory neural cells of the dorsal root ganglion and with low level in the skin (at protein level). Isoform 1 is expressed predominantly in the brain and spinal cord with low levels in the heart (PubMed:14581450). Isoform 2 is predominantly expressed in muscle and heart and with low levels in the brain. Isoform 5 is expressed in the skin and with low levels in myoblast cells. Isoform 6 is expressed in neurons. Isoform 7 is expressed in lung and with low levels in the brain.|||Isoform 1 is the major form expressed in the dorsal root ganglia at 14.5 dpc. Isoform 2 is predominantly expressed in the myocardium, skeletal muscles, bone cartilage and epithelia of the tongue at 14.5 dpc. Isoform 5 is expressed at high levels in the epidermis and mucosal epithelia of the digestive tracts at 14.5 dpc.|||Its association with epidermal and simple keratins is dependent on the tertiary structure induced by heterodimerization of these intermediate filaments proteins and most likely involves recognition sites located in the rod domain of these keratins.|||Many conflicts and frameshifts that might be strain-specific.|||Membrane|||Mice show progressive deterioration in motor function and sensory neurodegeneration. Exhibit axonal swellings packed with disorganized intermediate filaments (IFs) and microtubules. Show poorly defined Z lines and display a reduction in sarcomere length. Have increased accumulation of vesicles and severely disrupted retrograde axonal transport. In stratified epithelia, hemidesmosomes are normal but they lack the inner plate and have no cytoskeleton attached.|||Nucleus|||Nucleus envelope|||Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.|||Required for bundling actin filaments around the nucleus.|||The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.|||Z line|||axon|||cell cortex|||cytoskeleton|||hemidesmosome|||sarcolemma|||stress fiber http://togogenome.org/gene/10090:Atrn ^@ http://purl.uniprot.org/uniprot/Q9WU60 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Heavily glycosylated.|||Involved in the initial immune cell clustering during inflammatory response and may regulate chemotactic activity of chemokines (By similarity). May play a role in melanocortin signaling pathways that regulate energy homeostasis and hair color. Low-affinity receptor for agouti. Has a critical role in normal myelination in the central nervous system (By similarity).|||Monomer and homotrimer. http://togogenome.org/gene/10090:B3galt1 ^@ http://purl.uniprot.org/uniprot/O54904|||http://purl.uniprot.org/uniprot/Q505A3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-galactosyltransferase that transfers galactose from UDP-alpha-D-galactose to substrates with a terminal beta-N-acetylglucosamine (beta-GlcNAc) residue. Involved in the biosynthesis of the carbohydrate moieties of glycolipids and glycoproteins.|||Golgi apparatus membrane|||Membrane|||Ubiquitous. http://togogenome.org/gene/10090:Sestd1 ^@ http://purl.uniprot.org/uniprot/Q80UK0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the SOLO family.|||Interacts (via the spectrin 1 repeat) with TRPC4 and TRPC5 (via CIRB domain). Interacts with CTNNB1.|||May act as the primary docking protein directing membrane turnover and assembly of the transient receptor potential channels TRPC4 and TRPC5. Binds phospholipids such as phosphatidylinositol monophosphates, phosphatidylinositol diphosphates (PIP2s) and phosphatidic acid, but not less polar lipids including phosphatidylcholine, phosphatidylserine, and phosphatidylinositol. The binding to PIP2s is calcium dependent. Might be involved in the plasma membrane localization of CTNNB1 (By similarity). http://togogenome.org/gene/10090:Lcn3 ^@ http://purl.uniprot.org/uniprot/Q14AJ3|||http://purl.uniprot.org/uniprot/Q62471 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted|||Specifically expressed in vomeronasal and posterior glands of the nasal septum, the ducts of which open into the lumen of the vomeronasal organ.|||Transport of lipophilic molecules, possible pheromone-carrier. http://togogenome.org/gene/10090:Hps1 ^@ http://purl.uniprot.org/uniprot/O08983 ^@ Disease Annotation|||Function|||Subunit|||Tissue Specificity ^@ Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38.|||Component of the biogenesis of lysosome-related organelles complex-3 (or BLOC-3), a heterodimer of HPS1 and HPS4. HPS1 cannot but BLOC-3 complex (heterodimer of HPS1 and HPS4) can interact with the GTP-bound form of RAB9A and RAB9B. HPS1 and BLOC-3 complex do not interact with the GDP-bound form of RAB9A and RAB9B.|||Defects in Hps1 are the cause of the pale ear (ep) mutant which exhibits hypopigmentation associated with defects of multiple cytoplasmic organelles, including melanosomes, lysosomes, and granular elements of platelets (PubMed:9256466).|||Expressed in all tissues examined with the possible exception of skeletal muscle. The highest expression was observed in lung, liver, kidney and spleen. http://togogenome.org/gene/10090:Pitpnc1 ^@ http://purl.uniprot.org/uniprot/Q8K4R4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PtdIns transfer protein family. PI transfer class IIB subfamily.|||Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes (By similarity). Binds PA derived from the phospholipase D signaling pathway and among the cellular PA species, preferably binds to the C16:0/16:1 and C16:1/18:1 PA species (By similarity).|||Cytoplasm|||Nucleus|||Specifically binds to phosphatidylinositol but not to other phospholipids and may play a role in the phosphoinositide-mediated signaling in the neural development.|||Weakly expressed in brain and is rather confined to the embryonic stage.|||Widely expressed in brain, with expression in the gray matters of pre- and postnatal brains. http://togogenome.org/gene/10090:Hcfc1r1 ^@ http://purl.uniprot.org/uniprot/Q9CYQ5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with HCFC1.|||Nucleus|||Regulates HCFC1 activity by modulating its subcellular localization. Overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm. HCFC1R1-mediated export may provide the pool of cytoplasmic HCFC1 required for import of virion-derived VP16 into the nucleus (By similarity). http://togogenome.org/gene/10090:Irf5 ^@ http://purl.uniprot.org/uniprot/F6Z6C6|||http://purl.uniprot.org/uniprot/P56477|||http://purl.uniprot.org/uniprot/Q3U169 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Lys-63'-linked polyubiquitination by TRAF6 is required for activation.|||Belongs to the IRF family.|||Cytoplasm|||Homodimer, when phosphorylated (PubMed:25326420). Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (By similarity). Interacts with MYD88 and TRAF6 (PubMed:15665823).|||Maintained as a monomer in an autoinhibited state (PubMed:25326420). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (By similarity). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326420).|||Mice develop normally and no overt phenotype is observed in hematopoietic cell population (PubMed:15665823). However, the induction of pro-inflammatory cytokines, such as interleukin-6 (IL6) and IL12 by various TLR ligands is impaired, whereas interferon-alpha induction is normal (PubMed:15665823).|||Nucleus|||Phosphorylation of serine and threonine residues by IKBKB in a C-terminal autoinhibitory region, stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/EP300 and initiation of transcription.|||Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:15665823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:15665823). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (PubMed:15665823). http://togogenome.org/gene/10090:Pou2f3 ^@ http://purl.uniprot.org/uniprot/P31362|||http://purl.uniprot.org/uniprot/Q3U5D1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family. Class-2 subfamily.|||Interacts (via the POU domain) with POU2AF1 and POU2AF2 in a DNA-dependent manner; this interaction recruits POU2AF2 to chromatin and increases POU2F3 transactivation activity.|||Mice homozygous for null mutation exhibit defective keratinocyte differentiation, however the skin and coat appear normal.|||Nucleus|||Skin, thymus, stomach and testis.|||Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') (PubMed:8441607). Regulates cell type-specific differentiation pathways. Involved in the regulation of keratinocytes differentiation (PubMed:9242494). The POU2F3-POU2AF2/POU2AF3 complex drives the expression of tuft-cell-specific genes, a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues (By similarity). http://togogenome.org/gene/10090:Cyb561 ^@ http://purl.uniprot.org/uniprot/Q60720|||http://purl.uniprot.org/uniprot/V9GX11 ^@ Cofactor|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly distributed in a number of neuroendocrine tissues.|||Binds 2 heme b groups non-covalently.|||Membrane|||Mice lacking Cyb561 have significantly decreased amounts of norepinephrine and normetanephrine in the adrenal gland and brain while the biosynthesis of dopamine, the norepinephrine precursor, is normal pointing to a defect in the catecholamine biosynthesis downstream of dopamine probably at the level of the dopamine beta synthase.|||Transmembrane reductase that uses ascorbate as an electron donor in the cytoplasm and transfers electrons across membranes to reduce monodehydro-L-ascorbate radical in the lumen of secretory vesicles (Probable). It is therefore involved the regeneration and homeostasis within secretory vesicles of ascorbate which in turn provides reducing equivalents needed to support the activity of intravesicular enzymes (By similarity).|||chromaffin granule membrane http://togogenome.org/gene/10090:Rhox6 ^@ http://purl.uniprot.org/uniprot/O70238 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Alox8 ^@ http://purl.uniprot.org/uniprot/O35936 ^@ Cofactor|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||By phorbol ester.|||Expressed in epidermis and brain (PubMed:9305900, PubMed:9518531). No expression found in heart, spleen, liver, skeletal muscle, kidney or testis.|||Membrane|||Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). Catalyzes the peroxidation of arachidonate and linoleate into (8S)-HPETE and (9S)-HPODE respectively (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). In addition to generate (8S)-HPETE from free arachidonic acid (AA), may produce other HETE isomers from phospholipid-esterified polyunsaturated fatty acids and minor products derived from (8S)-HPETE itself that may include leukotriene A4 and 8,15-diHPETE (PubMed:16143298, PubMed:16112079, PubMed:27435673). With free arachidonate as substrate, has no detectable 15S-lipoxygenase activity and only displays a 8S-lipoxygenase activity (PubMed:10625675, PubMed:16112079, PubMed:16143298, PubMed:15558016, PubMed:10965849, PubMed:9305900). However may have a 15S-lipoxygenase activity with (8S)-HPETE to produce (8S,15S)-diHPETE and when oxidizes directly arachidonic acid esterified to membrane-bound phospholipids to produce a phospholipid-esterified 15-HpETE (PubMed:27435673, PubMed:16112079, PubMed:16143298). May also catalyze (15S)-HPETE peroxidation to produce 8,15-diHPETE (PubMed:16112079). May play a role in keratinocyte differentiation through activation of the peroxisome proliferator activated receptor signaling pathway (PubMed:10965849).|||The PLAT domain can bind calcium ions; this promotes association with membranes.|||cytosol http://togogenome.org/gene/10090:Abhd5 ^@ http://purl.uniprot.org/uniprot/Q9DBL9 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acyltransferase activity is inhibited by detergents such as Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Acyltransferase activity is inhibited by the presence of magnesium and calcium.|||Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.|||Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group on a lysophosphatidic acid (PubMed:19801371). Functions preferentially with 1-oleoyl-lysophosphatidic acid followed by 1-palmitoyl-lysophosphatidic acid, 1-stearoyl-lysophosphatidic acid and 1-arachidonoyl-lysophosphatidic acid as lipid acceptor (PubMed:19801371). Functions preferentially with arachidonoyl-CoA followed by oleoyl-CoA as acyl group donors (PubMed:19801371). Functions in phosphatidic acid biosynthesis (By similarity). May regulate the cellular storage of triacylglycerol through activation of the phospholipase PNPLA2 (PubMed:16679289). Involved in keratinocyte differentiation (By similarity). Regulates lipid droplet fusion (PubMed:26083785).|||Cytoplasm|||Highly expressed in the adipose tissue and testes. Weakly expressed in the liver, muscle, kidney, and heart. Expressed by upper epidermal layers and dermal fibroblasts in skin, hepatocytes and hypothalamus in brain (at protein level).|||Interacts with ADRP (By similarity). Interacts with PLIN. Interacts with and PNPLA2. Interacts with PLIN5; promotes interaction with PNPLA2.|||Lipid droplet|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||cytosol http://togogenome.org/gene/10090:Spata1 ^@ http://purl.uniprot.org/uniprot/Q9D5R4 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detectable at postnatal day 24 (P24) and its expression is increased at day P30 and P35.|||Highly abundant in the testis, and is also expressed in the heart and kidney (at protein level).|||Interacts with IFT20.|||acrosome http://togogenome.org/gene/10090:Tnfrsf4 ^@ http://purl.uniprot.org/uniprot/B1ASL3|||http://purl.uniprot.org/uniprot/P47741 ^@ Caution|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By IL6/STAT3 signaling in T-helper Th17 cells.|||Expressed in CD4(+) T-cells and in T-helper Th17 cells (at protein level).|||Interacts with TRAF2, TRAF3 and TRAF5.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule implicated in long-term T-cell immunity (By similarity). http://togogenome.org/gene/10090:Allc ^@ http://purl.uniprot.org/uniprot/Q32MW4|||http://purl.uniprot.org/uniprot/Q9JHX6 ^@ Function|||Similarity ^@ Belongs to the allantoicase family.|||The function of this enzyme is unclear as allantoicase activity is not known to exist in mammals. http://togogenome.org/gene/10090:Map3k8 ^@ http://purl.uniprot.org/uniprot/Q07174|||http://purl.uniprot.org/uniprot/Q3UEB8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cytoplasm|||Expressed in bone marrow-derived macrophages, peritoneal macrophages, splenocytes and 3T3-L1 fibroblasts and differentiated adipocytes (at protein level). Highly expressed in adult submandibular gland, thymus, spleen and newborn digestive tract.|||Forms a ternary complex with NFKB1/p105 and TNIP2. Interacts with NFKB1; the interaction increases the stability of MAP3K8 but inhibits its MEK phosphorylation activity, whereas loss of interaction following LPS stimulation leads to its degradation. Interacts with CD40 and TRAF6; the interaction is required for ERK activation. Interacts with KSR2; the interaction inhibits ERK and NF-kappa-B activation.|||Mutant mice develop normally and show histologically normal bone marrow, thymus, spleen and lymph nodes. Mice are resistant to the induction of endotoxin shock due to defect in the induction of Tnf in response to LPS. Mice display impaired host defense against T.gondii with reduced parasite clearance and decreased Ifng production. Mice also show increased susceptibility to M.tuberculosis and L.monocytogenes infection.|||Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle.|||Up-regulated by Il12 in T-lymphocytes. Up-regulated during in vitro adipocyte differentiation. Up-regulated in epididymal adipose tissue of obese mice. http://togogenome.org/gene/10090:Tmem177 ^@ http://purl.uniprot.org/uniprot/Q8BPE4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM177 family.|||Found in a complex with COX20, COA6, MT-CO2/COX2, COX18, SCO1 and SCO2. Interacts with COX20. Interacts with COX1, MT-CO2/COX2, SCO1 and SCO2 in a COX20-dependent manner.|||Mitochondrion inner membrane|||Plays a role in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation and is required for the stabilization of COX20 and the newly synthesized MT-CO2/COX2 protein. http://togogenome.org/gene/10090:Reg3a ^@ http://purl.uniprot.org/uniprot/O09037 ^@ Disease Annotation|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a hormone in response to different stimuli like anti-inflammatory signals, such as IL17A, or gut microbiome. Secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways. Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury via activation of EXTL3-PI3K-AKT signaling pathway (By similarity). In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF (PubMed:22727489). In pancreas, is able to permealize beta-cells membrane and stimulate their proliferation (PubMed:36240759).|||Bactericidal C-type lectin. The lack of the EPN motif may explain its inability to bind peptidoglycan.|||Forms a hexameric membrane-permeabilizing oligomeric pore on membrane phospholipids. The hexamer is formed by three dimers related by helical symmetry. Forms filaments, filamentation traps pore complexes and limits damage to host cells. Interacts with EXTL3.|||IL17A induces its expression in primary keratinocytes and skin wounds.|||Lacks the EPN motif and the presence of Gln instead of Glu at amino-acid position 114 may explain its inability to bind peptidoglycan.|||Overexpressed during the acute phase of pancreatitis.|||Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.|||Secreted|||Small intestine and pancreas. http://togogenome.org/gene/10090:Tubb4b ^@ http://purl.uniprot.org/uniprot/P68372 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||The highly acidic C-terminal region may bind cations such as calcium.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Widely expressed. Expressed in the retina and the cochlea.|||cytoskeleton http://togogenome.org/gene/10090:Colgalt1 ^@ http://purl.uniprot.org/uniprot/Q8K297 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 25 family.|||Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen. By acting on collagen glycosylation, facilitates the formation of collagen triple helix. Also involved in the biosynthesis of collagen type IV.|||Endoplasmic reticulum lumen|||N-glycosylated. http://togogenome.org/gene/10090:Api5 ^@ http://purl.uniprot.org/uniprot/O35841|||http://purl.uniprot.org/uniprot/Q3UYQ4 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-251 impairs antiapoptotic function.|||Antiapoptotic factor that may have a role in protein assembly. Negatively regulates ACIN1. By binding to ACIN1, it suppresses ACIN1 cleavage from CASP3 and ACIN1-mediated DNA fragmentation. Also known to efficiently suppress E2F1-induced apoptosis (By similarity).|||Belongs to the API5 family.|||Cytoplasm|||Down-regulated in vascular smooth muscle cells (vSMCs) treated with benzo[a]pyrene (BaP).|||Monomer. Interacts with FGF2 and ACIN1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Drd5 ^@ http://purl.uniprot.org/uniprot/B2RQS5|||http://purl.uniprot.org/uniprot/Q8BLD9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.|||Membrane http://togogenome.org/gene/10090:Lemd3 ^@ http://purl.uniprot.org/uniprot/Q9WU40 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest (By similarity).|||Interacts with SMAD1, SMAD2, SMAD3 and SMAD5. Binds to both phosphorylated and unphosphorylated R-SMADS (By similarity).|||Nucleus inner membrane http://togogenome.org/gene/10090:Rad23b ^@ http://purl.uniprot.org/uniprot/P54728|||http://purl.uniprot.org/uniprot/Q3UQN3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAD23 family.|||Component of the XPC complex composed of XPC, RAD23B and CETN2. Interacts with NGLY1 and PSMC1. Interacts with ATXN3 (By similarity). Interacts with AMFR. Interacts with VCP; the interaction is indirect and mediated by NGLY1.|||Cytoplasm|||Impaired embryonic development with a 90 % rate of intrauterine or neonatal death. Surviving animals display a variety of abnormalities, including retarded growth, facial dysmorphology and male sterility. The effect on NER competence is reported conflictingly: According PubMed:11809813 no change in NER activity is found and according PubMed:15336624 a reduced NER activity is seen. Embryonic lethal with Rad23a and Rad23b double deficiency. Double deficient cells show reduced cell survival upopn UV radiation and reduced steady-state level of Xpc indicating a reduced NER capacity.|||Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with Cetn2 appears to stabilize Xpc. May protect Xpc from proteasomal degradation (By similarity).|||Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.|||Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Involved in nucleotide excision repair.|||Nucleus|||The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, Xpa, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the Xpc:Rad23b dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. Xpc:Rad23b contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. Xpc:Rad23bB induces a bend in DNA upon binding. Xpc:Rad23b stimulates the activity of DNA glycosylases Tdg and Smug1 (By similarity). http://togogenome.org/gene/10090:Ddx1 ^@ http://purl.uniprot.org/uniprot/Q91VR5 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double-strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation (By similarity). Acts as a positive transcriptional regulator of cyclin CCND2 expression (PubMed:19398953). Binds to the cyclin CCND2 promoter region (PubMed:19398953). Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (PubMed:21703541). Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (PubMed:21703541).|||Belongs to the DEAD box helicase family. DDX1 subfamily.|||Cytoplasm|||Cytoplasmic granule|||Expressed in the testis from 11.5 to 19.5 dpc.|||Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation (PubMed:21703541). Interacts with DHX36 (PubMed:21703541). Interacts (via B30.2/SPRY domain) with DDX21 (via N-terminus); this interaction serves as bridges to TICAM1 (PubMed:21703541). Interacts with FAM98A (via N- and C-terminus) (By similarity). Interacts with MBNL1 (By similarity). Interacts with CSTF2 (By similarity). Interacts with HNRNPK (By similarity). Interacts with ATM (By similarity). Interacts with RELA (via C-terminus) (By similarity). Component of the tRNA-splicing ligase complex (By similarity). Interacts with PHF5A (via C-terminus) (PubMed:18758164). Interacts with PQBP1 (By similarity). Interacts with ERCC6 (By similarity).|||Mitochondrion|||Nucleus|||Phosphorylated by ATM kinase; phosphorylation is increased in response to ionizing radiation (IR).|||Testis-specific. Expressed in the germ line stem cells, spermatogonia and spermatocytes of the testis. Also expressed in the seminoma and nonseminoma types of testicular germ cell tumors (TGCTs) (at protein level).|||The helicase domain is involved in the stimulation of RELA transcriptional activity.|||cytosol http://togogenome.org/gene/10090:Tigd3 ^@ http://purl.uniprot.org/uniprot/Q7TM95 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tigger transposable element derived protein family.|||Nucleus http://togogenome.org/gene/10090:Adrb2 ^@ http://purl.uniprot.org/uniprot/P18762 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB2 sub-subfamily.|||Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.|||Binds NHERF1 and GPRASP1. Interacts with ARRB1 and ARRB2. Interacts with SRC (By similarity). Interacts with USP20 and USP33 (By similarity). Interacts with VHL; the interaction, which is increased on hydroxylation of ADRB2, ubiquitinates ADRB2 leading to its degradation. Interacts with EGLN3; the interaction hydroxylates ADRB2 facilitating VHL-E3 ligase-mediated ubiquitination. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. Interacts with CNIH4. Interacts with ARRDC3. Interacts with NEDD4 (By similarity). Interacts with MARCHF2 (By similarity).|||Cell membrane|||Early endosome|||Golgi apparatus|||Hydroxylation by EGLN3 occurs only under normoxia and increases the interaction with VHL and the subsequent ubiquitination and degradation of ADRB2.|||Palmitoylated. Mainly palmitoylated at Cys-341. Palmitoylation may reduce accessibility of phosphorylation sites by anchoring the receptor to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation. Also undergoes transient, ligand-induced palmitoylation at Cys-265 probably by ZDHHC9, ZDHHC14 and ZDHHC18 within the Golgi. Palmitoylation at Cys-265 requires phosphorylation by PKA and receptor internalization and stabilizes the receptor. Could be depalmitoylated by LYPLA1 at the plasma membrane.|||Palmitoylated; may reduce accessibility of Ser-345 and Ser-346 by anchoring Cys-341 to the plasma membrane. Agonist stimulation promotes depalmitoylation and further allows Ser-345 and Ser-346 phosphorylation (By similarity).|||Phosphorylated by PKA and BARK upon agonist stimulation, which mediates homologous desensitization of the receptor. PKA-mediated phosphorylation seems to facilitate phosphorylation by BARK.|||Phosphorylation of Tyr-141 is induced by insulin and leads to supersensitization of the receptor.|||Polyubiquitinated. Agonist-induced ubiquitination leads to sort internalized receptors to the lysosomes for degradation. Deubiquitination by USP20 and USP33, leads to ADRB2 recycling and resensitization after prolonged agonist stimulation. USP20 and USP33 are constitutively associated and are dissociated immediately after agonist stimulation. Ubiquitination by the VHL-E3 ligase complex is oxygen-dependent (By similarity). http://togogenome.org/gene/10090:Tnk1 ^@ http://purl.uniprot.org/uniprot/Q99ML2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Cytoplasm|||Expressed in whole embryo and all adult tissues examined including liver, kidney, heart, brain, skeletal muscle and intestine. Also detected in various myeloid- and lymphoid-derived cell lines.|||Expression during embryogenesis increases between 7 dpc and 11 dpc. Levels of expression subsequently decrease and reach a steady-state level by 17 dpc.|||Interacts with the SH3 domain of PLCG1 via its Pro-rich domain.|||May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction (By similarity). Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway.|||Membrane|||Mice develop spontaneous tumors, including lymphomas and carcinomas at high rates. http://togogenome.org/gene/10090:Hdc ^@ http://purl.uniprot.org/uniprot/P23738 ^@ Function|||Similarity|||Subunit ^@ Belongs to the group II decarboxylase family.|||Catalyzes the biosynthesis of histamine from histidine.|||Homodimer. http://togogenome.org/gene/10090:Vmn2r62 ^@ http://purl.uniprot.org/uniprot/K7N712 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrpl20 ^@ http://purl.uniprot.org/uniprot/Q9CQL4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL20 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity). Interacts with OXA1L (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Or4c121 ^@ http://purl.uniprot.org/uniprot/Q8VGM5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adgra2 ^@ http://purl.uniprot.org/uniprot/Q91ZV8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the vasculature of the developing embryo (PubMed:11559528, PubMed:21071672, PubMed:21282641). Expression in normal adult tissues is specifically vascular with endothelial expression in CNS, including brain and retina and more widespread pericyte expression in the brain and organs, including the kidney, pancreas and corpus luteum (PubMed:21071672).|||At 10 dpc expressed in a wide variety of tissues with relatively more abundant expression in limb buds (PubMed:18848646). At 10.5-12.5 dpc, detected in vessels of the developing CNS and perineural vascular plexus (PNVP) (PubMed:21282641). Expressed in both endothelial cells and pericytes, most prominently in brain and neural tube, and to a lesser degrees in non-CNS embryonic organs, including the liver, heart, and kidney (PubMed:18848646, PubMed:21282641). Expressed also in embryonic epithelium of lung and esophagus and in mesenchyme (PubMed:18848646, PubMed:21282641). Detected in mesenchyme of the palatal shelf at 12.5 dpc (PubMed:21282641).|||Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:25373781, PubMed:25558062, PubMed:28803732). Plays a key role in Wnt7-specific responses, such as endothelial cell sprouting and migration in the forebrain and neural tube, and establishment of the blood-brain barrier (PubMed:21071672, PubMed:21282641, PubMed:21421844, PubMed:25373781, PubMed:28288111). Acts as a Wnt7-specific coactivator of canonical Wnt signaling: required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (By similarity). ADGRA2-tethering function does not rely on its G-protein coupled receptor (GPCR) structure but instead on its combined capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly (By similarity). Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate (By similarity).|||Glycosylated.|||Interacts with RECK; the interaction is direct (PubMed:28803732). Interacts (via PDZ-binding motif) with DLG1 (via PDZ domains) (PubMed:25558062). The cleaved extracellular subunit interacts with the integrin heterodimer ITGAV:ITGB3 (By similarity).|||It is uncertain whether Met-1 or Met-8 is the initiator.|||No viable adults (PubMed:21071672, PubMed:21282641, PubMed:21421844). Beginning at 11 dpc, deficient embryos exhibit completely penetrant, progressive CNS hemorrhage originating in forebrain telencephalon and ventral neural tube leading to embryonic lethality from 15.5 dpc (PubMed:21071672, PubMed:21282641, PubMed:21421844). Embryos at 11.5 dpc display selective CNS-specific vascular patterning defects, with markedly reduced angiogenic sprouting into the forebrain telencephalon and thickening of the underlying periventricular vascular plexus rendering the telencephalon virtually avascular (PubMed:21071672, PubMed:21282641, PubMed:21421844, PubMed:25373781). Remaining CNS vessels show significantly increased permeability (PubMed:21421844). Lung size is reduced in 15.5 dpc embryos (PubMed:21282641). Cleft palate is present at 15.5 dpc or later (PubMed:21282641). Conditional knockout mice lacking Adgra2 in the endothelia of adult mice show blood-brain barrier integrity defects in a stroke model and glioblastoma (PubMed:28288111).|||Proteolytically cleaved into two subunits, an extracellular subunit and a seven-transmembrane subunit. Cleaved by thrombin (F2) and MMP1. Also cleaved by MMP9, with lower efficiency. Presence of the protein disulfide-isomerase P4HB at the cell surface is additionally required for shedding of the extracellular subunit, suggesting that the subunits are linked by disulfide bonds. Shedding is enhanced by the growth factor FGF2 and may promote cell survival during angiogenesis.|||The RGD motif is involved in integrin ITGAV:ITGB3 binding.|||The leucine-rich repeats (LRRs) are important for potentiation of Wnt7 signaling.|||Up-regulated by the growth factors activin AB (INHBA: INHBB dimer) and TGFB1 in vitro.|||filopodium http://togogenome.org/gene/10090:Ccl5 ^@ http://purl.uniprot.org/uniprot/P30882|||http://purl.uniprot.org/uniprot/Q5XZF2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. May also be an agonist of the G protein-coupled receptor GPR75. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells.|||Secreted|||T-cell and macrophage specific. http://togogenome.org/gene/10090:Comtd1 ^@ http://purl.uniprot.org/uniprot/Q8BIG7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.|||Homodimer.|||Membrane|||Putative O-methyltransferase. http://togogenome.org/gene/10090:Rfxap ^@ http://purl.uniprot.org/uniprot/Q8VCG9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of the RFX complex that binds to the X-box of MHC II promoters.|||Phosphorylated.|||RFX consists of at least 3 different subunits; RFXAP, RFX5 and RFX-B/RFXANK; with each subunit representing a separate complementation group. RFX forms cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX associates with CIITA to form an active transcriptional complex (By similarity). http://togogenome.org/gene/10090:Slc39a11 ^@ http://purl.uniprot.org/uniprot/Q8BWY7 ^@ Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||Golgi apparatus|||Highly expressed in the testes and portions of the digestive system including the stomach, ileum and cecum. In contrast, expressed at very low levels in liver, duodenum, jejunum, and colon.|||Nucleus|||Transcriptionally up-regulated by zinc (PubMed:23643525). Up-regulated during lactation.|||Zinc importer that regulates cytosolic zinc concentration either via zinc influx from the extracellular compartment or efflux from intracellular organelles such as Golgi apparatus. May transport copper ions as well. The transport mechanism remains to be elucidated. http://togogenome.org/gene/10090:1700066M21Rik ^@ http://purl.uniprot.org/uniprot/Q9D9H8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the C2orf69 family.|||May play a role in the respiratory chain.|||Mitochondrion matrix http://togogenome.org/gene/10090:Clasp2 ^@ http://purl.uniprot.org/uniprot/Q8BRT1|||http://purl.uniprot.org/uniprot/Q8BSE7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CLASP family.|||Cell membrane|||Expressed in oocytes and early embryos.|||Golgi apparatus|||Highly expressed in brain and at low levels in heart, kidney and lung.|||Interacts with microtubules (PubMed:11290329). Interacts with MAPRE1; probably required for targeting to growing microtubule plus ends. Interacts with ERC1, MAPRE3 and PHLDB2. The interaction with ERC1 may be mediated by PHLDB2. Interacts with GCC2; recruits CLASP2 to Golgi membranes (By similarity). Interacts with CLIP2 and RSN (PubMed:11290329). Interacts with MACF1 (PubMed:18854161).|||Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex.|||Phosphorylated by GSK3B. Phosphorylation by GSK3B may negatively regulate binding to microtubule lattices in lamella. Isoform 2 is phosphorylated on Ser-241.|||The two SXIP sequence motifs mediate interaction with MAPRE1; this is necessary for targeting to growing microtubule plus ends.|||Two TOG regions display structural characteristics similar to HEAT repeat domains and mediate interaction with microtubules.|||centrosome|||cytoskeleton|||kinetochore|||ruffle membrane|||spindle|||spindle pole|||trans-Golgi network http://togogenome.org/gene/10090:Ppm1l ^@ http://purl.uniprot.org/uniprot/Q8BHN0 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6.|||Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Expressed in brain, heart, testis, liver, lung and skeletal muscle.|||Interacts with MAP3K7/TAK1 and MAP3K5.|||Membrane|||Mice exhibit increased fat mass and higher plasma glucose levels compared to wild type mice. Male mice also exhibit a decrease in free fatty acids and higher blood pressure. http://togogenome.org/gene/10090:Atp13a3 ^@ http://purl.uniprot.org/uniprot/Q5XF89 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-driven pump involved in endocytosis-dependent polyamine transport. Uses ATP as an energy source to transfer polyamine precursor putrescine from the endosomal compartment to the cytosol.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.|||Early endosome membrane|||Expression is greatest in liver, followed by kidney, colon, stomach, brain and small intestine. Isoform 1 is highly expressed in the kidney while isoform 2 is highly expressed in the brain.|||Late endosome membrane|||Recycling endosome membrane http://togogenome.org/gene/10090:Tmem144 ^@ http://purl.uniprot.org/uniprot/Q8VEH0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM144 family.|||Membrane http://togogenome.org/gene/10090:Slc30a4 ^@ http://purl.uniprot.org/uniprot/A2AK40|||http://purl.uniprot.org/uniprot/O35149 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Defect in Slc30a4 is the cause of the lethal milk (lm) phenotype. Mice with lm are defective in zinc transport into breast milk, due to a premature translation termination codon at position 297. Only homozygous mutant adults develop dermatitis, skin lesions, and hair loss due to a systemic zinc deficiency. Pups of any genotype suckled on homozygous mutant female also develop symptoms characteristic of nutritional zinc deficiency, including dermatitis, alopecia and stunted growth.|||Endosome membrane|||Homodimerization could regulate efficiency for zinc transport. Interacts with TMEM163 (By similarity).|||Late endosome membrane|||Lysosome membrane|||Membrane|||Probable proton-coupled zinc ion antiporter mediating zinc import from cytoplasm potentially into the endocytic compartment (PubMed:9354792). Controls zinc deposition in milk (PubMed:9354792).|||Widely expressed. Highly expressed in the brain and in mammary epithelial cell lines. http://togogenome.org/gene/10090:Pabir1 ^@ http://purl.uniprot.org/uniprot/Q9DB52 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an inhibitor of serine/threonine-protein phosphatase 2A (PP2A) activity. Potentiates ubiquitin-mediated proteasomal degradation of serine/threonine-protein phosphatase 2A catalytic subunit alpha (PPP2CA) (By similarity). Inhibits PP2A-mediated dephosphorylation of WEE1, promoting ubiquitin-mediated proteolysis of WEE1, thereby releasing G2/M checkpoint (By similarity).|||Belongs to the FAM122 family.|||CHEK1-mediated phosphorylation at Ser-34 negatively regulates its ability to inhibit serine/threonine-protein phosphatase 2A (PP2A) activity. Phosphorylation leads to its release from the PP2A complex and its sequestration by 14-3-3 proteins in the cytoplasm resulting in its inability to translocate to the nucleus, where it otherwise inhibits PP2A.|||Cytoplasm|||Interacts with PPP2CA, PPP2R2A and PPP2R1A (By similarity). The CHEK1-mediated Ser-34 phosphorylated form interacts with 14-3-3 proteins (By similarity).|||Nucleus http://togogenome.org/gene/10090:Rundc3a ^@ http://purl.uniprot.org/uniprot/O08576 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RUNDC3 family.|||Brain.|||Interacts with the GTP-bound form of RAP2A.|||May act as an effector of RAP2A in neuronal cells. http://togogenome.org/gene/10090:Cldn5 ^@ http://purl.uniprot.org/uniprot/O54942 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Cell membrane|||Interacts with MPDZ (By similarity). Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||Widely expressed with highest levels in the lung.|||tight junction http://togogenome.org/gene/10090:Agxt ^@ http://purl.uniprot.org/uniprot/O35423|||http://purl.uniprot.org/uniprot/Q3UEN9 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the transamination between L-serine and pyruvate and weakly contributes to gluconeogenesis from the L-serine metabolism.|||Catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification.|||Homodimer.|||Mitochondrion matrix|||Peroxisome|||The intracellular compartmentalization of AGTX in mammalian hepatocytes is species dependent. In human and rabbit, AGTX is peroxisomal. In new world monkeys (marmoset) and rodents (rat and mouse), it is distributed approximately evenly between peroxisomes and mitochondria. In carnivores, like cat, the great majority of the enzyme is mitochondrial with only a small proportion being peroxisomal. http://togogenome.org/gene/10090:Bcl11a ^@ http://purl.uniprot.org/uniprot/Q9QYE3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Germline biallelic loss of Bcl11a leads to perinatal lethality. Bcl11a +/- mice have a significantly decreased brain volume, affecting both gray and white matter. The limbic system (hippocampus and amygdala) is among the brain regions that are more severely affected. Bcl11a +/- mice display normal novelty-seeking behavior but show long-term social memory defects, impaired sociability, and increased physical activity. Bcl11a +/- mice show dynamic postnatal transcriptional dysregulation in the brain.|||Highly expressed in the developing embryo. Expressed in developing brain from 10.5 dpc, with highest expression in the forebrain between 12.5 dpc and 14.5 dpc. Central nervous system expression persists throughout the postnatal period in the cortex, hippocampus, olfactory buld, and, to a lesser extent, in the cerebellum.|||Interacts with NR2F1, PIAS3, NR2F2 and NR2F6 (PubMed:18681895, PubMed:10744719). Interacts with TBR1 (By similarity).|||Isoforms are expressed in a tissue-specific fashion. Isoforms 1, isoform 2, and isoform 3 are expressed at similar levels in testis, kidney and spleen. Isoform 1 is expressed in the stomach, and isoform 2 is expressed exclusively in the lung. Overexpression following proviral integration in hematopoietic cells results in the generation of myeloid leukemia.|||Nucleus|||Sumoylated with SUMO1.|||The N-terminus is involved in protein dimerization and in transactivation of transcription.|||Transcription factor (By similarity). Associated with the BAF SWI/SNF chromatin remodeling complex (PubMed:23644491). Binds to the 5'-TGACCA-3' sequence motif in regulatory regions of target genes (By similarity). May play a role in hematopoiesis (PubMed:10757802). Essential factor in lymphopoiesis, required for B-cell formation in fetal liver (PubMed:12717432). May function as a modulator of the transcriptional repression activity of NR2F2 (PubMed:10744719).|||Zinc finger domains are necessary for sequence-specific binding to DNA. http://togogenome.org/gene/10090:Tacr2 ^@ http://purl.uniprot.org/uniprot/P30549|||http://purl.uniprot.org/uniprot/Q3KP20|||http://purl.uniprot.org/uniprot/Q8BZV9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P. http://togogenome.org/gene/10090:Fkbp4 ^@ http://purl.uniprot.org/uniprot/P30416 ^@ Activity Regulation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homodimer (By similarity). Interacts with GLMN (By similarity). Associates with HSP90AA1 and HSPA1A/HSPA1B in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex. Associates with tubulin. Interacts with MAPT/TAU (By similarity). Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; contributes to NR3C1 transport to the nucleus.|||Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria.|||Inhibited by FK506.|||Mitochondrion|||Nucleus|||Phosphorylation by CK2 results in loss of HSP90 binding activity.|||The C-terminal region (AA 375-458) is required to prevent tubulin polymerization.|||The PPIase activity is mainly due to the first PPIase FKBP-type domain (1-138 AA).|||The TPR repeats mediate mitochondrial localization.|||The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400.|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Igdcc3 ^@ http://purl.uniprot.org/uniprot/Q8BQC3 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. DCC family.|||Detected in cerebellum, kidney, heart, lung, skeletal muscle and spleen.|||Membrane|||Strongly expressed in embryos from 9.5 dpc to 10.5 dpc. Expression is much lower at 11.5 dpc and virtually extinct at 15.5 dpc. Detected in neural tube and lateral mesoderm at 9.5 dpc. At 10.5 dpc detected in fore and hind limb buds and lateral plate mesoderm, throughout the neural tube, in mesencephalon and dorsal diencephalon. http://togogenome.org/gene/10090:Pik3r1 ^@ http://purl.uniprot.org/uniprot/P26450|||http://purl.uniprot.org/uniprot/Q80UI5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the PI3K p85 subunit family.|||Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues (PubMed:27708159). Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity). Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348926).|||Double knockouts for KBTBD2 and PIK3R1 have increased body weight, normal fat storage, blood glucose and insulin levels.|||Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts (via SH2 domains) with CCDC88A/GIV (tyrosine-phosphorylated form); the interaction enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (By similarity). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner (PubMed:20348926). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with IRS1 and phosphorylated IRS4. Interacts with NISCH and RUFY3 (By similarity). Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR or BCR activation. Interacts with CBLB. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with SOCS7 and HCST. Interacts with AXL, FASLG, FGR, HCK, KIT and BCR. Interacts with PTK2/FAK1 (By similarity). Interacts with PDGFRB (tyrosine phosphorylated) (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with FER. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated) (Probable). Interacts with PDGFRA (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity. Interacts with ERBB4. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with APPL1 and APPL2 (PubMed:25328665). Interacts with SRC (By similarity). Interacts with ALOX5; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (By similarity). Interacts with TYK2 (By similarity). Interacts with nephrin NPHN1; the interaction is reduced by high glucose levels (By similarity).|||In adipose tissue, polyubiquitinated by the BCR(KBTBD2) E3 ubiquitin ligase complex; recognized by KBTBD2 through the SH2 domains, undergoes 'Lys-48'-linked polyubiquitination leading to its degradation.|||Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Dephosphorylated by PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear. Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR (By similarity). Phosphorylated by CSF1R. Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by TEK/TIE2.|||Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.|||The SH3 domain mediates the binding to CBLB. http://togogenome.org/gene/10090:Slc1a5 ^@ http://purl.uniprot.org/uniprot/Q3UFR4|||http://purl.uniprot.org/uniprot/Q9ESU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.|||Membrane http://togogenome.org/gene/10090:Ercc6 ^@ http://purl.uniprot.org/uniprot/F8VPZ5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A C-terminal ubiquitin-binding domain (UBD) is essential for transcription-coupled nucleotide excision repair activity, interaction with RNA polymerase II, association with chromatin after UV irradiation and for mediating the UV-induced translocation of ERRC8 to the nuclear matrix.|||Belongs to the SNF2/RAD54 helicase family.|||Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (By similarity). Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA (By similarity). It is required for transcription-coupled repair complex formation. It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the sites of RNA polymerase II-blocking lesions (By similarity). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (By similarity). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (By similarity). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing the premature exit from the G2/M checkpoint (By similarity). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (By similarity). Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (By similarity). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (By similarity). Involved in UV-induced translocation of ERCC8 to the nuclear matrix (By similarity). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (By similarity).|||Homodimer (By similarity). Binds DNA (By similarity). Interacts with ERCC8 (By similarity). Interacts with RNA polymerase II; interaction is enhanced by UV irradiation (By similarity). Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (By similarity). Interacts with KIAA1530/UVSSA (By similarity). Interacts with ELOA and CUL5; the interaction is induced by DNA damaging agents or by inhibitors of RNA polymerase II elongation (By similarity). Interacts (via WHD region) with RIF1 (By similarity). Interacts with SMARCC2/BAF170, SMARCB1/BAF47 and the neuron-specific chromatin remodeling complex (nBAF complex) (By similarity). Interacts with ERCC5/XPG (via C-terminus); the interaction stimulates ERCC6/CSB binding to DNA repair bubble and ERCC6/CSB ATPase activity (By similarity). May form a complex composed of RNA polymerase II, ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble during transcription-coupled nucleotide excision repair (By similarity). Interacts with CAND1, CSTF1, DDX3X, DDX5, DDX17, DDX23, DHX36, HDAC1, HNRNPU, MTA2, PRPF3, PSMD3, RBBP4, SFPQ, SMARCA1, SMARCA2, TOP1, USP7 and XRCC5 (By similarity).|||Nucleus|||Phosphorylated in a cell cycle-dependent manner at Ser-158 by cyclin A-CDK2 in response to DNA damage (By similarity). Phosphorylation at this site promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (By similarity). Phosphorylation is essential for its chromatin remodeling activity (By similarity).|||The N-terminal domain exerts an inhibitory effect on the helicase ATP-binding domain in such a manner that its ATPase activity is restricted (By similarity). Phosphorylation at Ser-158 promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (By similarity).|||Ubiquitinated at the C-terminus (By similarity). Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a UV-dependent manner (By similarity). Stabilized following interaction with KIAA1530/UVSSA, which promotes recruitment of deubiquitinating enzyme USP7, leading to deubiquitination of ERCC6 thereby preventing UV-induced degradation of ERCC6 by the proteasome (By similarity). http://togogenome.org/gene/10090:Ctu2 ^@ http://purl.uniprot.org/uniprot/Q3U308 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTU2/NCS2 family.|||Component of a complex at least composed of URM1, CTU2/NCS2 and CTU1/ATPBD3.|||Cytoplasm|||Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). May act by forming a heterodimer with CTU1/ATPBD3 that ligates sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position. http://togogenome.org/gene/10090:Vmn1r242 ^@ http://purl.uniprot.org/uniprot/K9J7G4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Crtc2 ^@ http://purl.uniprot.org/uniprot/Q3U182 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Asymmetric dimethylation of arginine resisues by PRMT6 enhances the association of CRTC2 with CREB on the promoters of gluconeogenic genes.|||Belongs to the TORC family.|||Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1. 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction. Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1. Interacts with SIK2 (By similarity). Interacts with 14-3-3 proteins, YWHAB and YWHAG (PubMed:28235073). Interacts (probably when phosphorylated at Ser-171) with YWHAE (PubMed:30611118). Interacts with calmodulin-dependent catalytic subunit PPP3CA/calcineurin A (PubMed:30611118). Interaction with COP1 mediates nuclear export and degradation of CRTC2 (PubMed:17805301).|||Cytoplasm|||Expressed in the suprachiasmatic nucleus (SCN) of the brain.|||Nucleus|||Phosphorylation/dephosphorylation states of Ser-171 are required for regulating transduction of CREB activity (PubMed:29211348). CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site (PubMed:29211348). This primary site of phosphorylation, is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs (SIK1 and SIK2) by LKB1 (By similarity). Following adenylyl cyclase activation, dephosphorylated at Ser-171 by PPP3CA/calcineurin A resulting in CRTC2 dissociation from 14-3-3 proteins and PPP3CA (PubMed:30611118). Phosphorylation at Ser-275 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx (By similarity). Both insulin and AMPK increase this phosphorylation of CRTC2 while glucagon suppresses it (By similarity). Phosphorylation at Ser-275 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm (By similarity).|||Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites (PubMed:29211348). Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated (PubMed:29211348). Acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells (By similarity). http://togogenome.org/gene/10090:Vmn1r158 ^@ http://purl.uniprot.org/uniprot/G3UY92 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Uckl1 ^@ http://purl.uniprot.org/uniprot/Q91YL3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the uridine kinase family.|||Cytoplasm|||Interacts with RNF19B.|||May contribute to UTP accumulation needed for blast transformation and proliferation.|||Nucleus|||Ubiquitinated by RNF19B; which induces proteasomal degradation. http://togogenome.org/gene/10090:Cdk18 ^@ http://purl.uniprot.org/uniprot/Q04899|||http://purl.uniprot.org/uniprot/Q0VDL6 ^@ Caution|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||In brain, kidney, intestine and at a much lower level, in fetal tissues.|||It is uncertain whether Met-1 or Met-4 is the initiator.|||May play a role in signal transduction cascades in terminally differentiated cells. http://togogenome.org/gene/10090:Kprp ^@ http://purl.uniprot.org/uniprot/B2RUR4 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Itih1 ^@ http://purl.uniprot.org/uniprot/F8WJ05|||http://purl.uniprot.org/uniprot/Q61702 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ITIH family.|||Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.|||I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (HC) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of ITIH1/HC1, ITIH2/HC2 and bikunin. Interacts with TNFAIP6 (via Link and CUB domains).|||Liver specific.|||May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.|||Secreted|||The S-linked glycan is composed of two 6-carbon sugars, possibly Glc or Gal. http://togogenome.org/gene/10090:Slc18b1 ^@ http://purl.uniprot.org/uniprot/E9PU92 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Psmb9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J256|||http://purl.uniprot.org/uniprot/P28076 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.|||Belongs to the peptidase T1B family.|||Component of the proteasome complex.|||Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.|||Cytoplasm|||Depletion of LMP2 by RNAi suppresses expression and activities of the matrix metalloproteinase MMP2 and MMP9 by blocking the transfer of active NF-kappa-B heterodimers into the nucleus.|||Detected in liver (at protein level). Expressed at high levels in the thymus, spleen, lung, heart and liver. Expressed at moderate levels in the kidney.|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB6. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Interacts with NCOA1, NCOA2 and NCOA3.|||The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Contributes to NFKBIA degradation and subsequently NFKB1 generation.|||Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Up-regulated by heat shock treatment. Down-regulated by EGR1 in neuronal cells. http://togogenome.org/gene/10090:Nkx2-9 ^@ http://purl.uniprot.org/uniprot/O70584 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NK-2 homeobox family.|||Nucleus|||Possible role in the specification of a distinct subset of neurons.|||Prominent expression in ventral brain and neural tube structures. http://togogenome.org/gene/10090:H6pd ^@ http://purl.uniprot.org/uniprot/Q8CFX1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes (PubMed:4169027, PubMed:12831846, PubMed:16356929, PubMed:18222920). Has a hexose-6-phosphate dehydrogenase activity, with broad substrate specificity compared to glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the pentose phosphate pathway (PubMed:4169027, PubMed:12831846, PubMed:18222920). In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway (PubMed:12831846). May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate (PubMed:12831846). The main function of this enzyme is to provide reducing equivalents such as NADPH to maintain the adequate levels of reductive cofactors in the oxidizing environment of the endoplasmic reticulum (PubMed:12831846, PubMed:16356929, PubMed:17656460, PubMed:18222920). By producing NADPH that is needed by reductases of the lumen of the endoplasmic reticulum like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity (PubMed:16356929).|||Endoplasmic reticulum lumen|||Expressed in liver (at protein level) (PubMed:4169027). Expressed in muscles (PubMed:18222920). Expressed in adipose tissues (PubMed:18218694).|||Homodimer.|||In the C-terminal section; belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.|||In the N-terminal section; belongs to the glucose-6-phosphate dehydrogenase family.|||Mice lacking H6pd are born at the expected Mendelian frequency and do not show overt phenotype (PubMed:16356929). However, they display cellular inability to convert 11-dehydrocorticosterone (11-DHC) to corticosterone and present increased corticosterone to 11-DHC conversion associated with adrenal hyperplasia (PubMed:16356929). Mutant mice also display fasting hypoglycemia and perturbed lipid mobilization that are probably due to the aforementioned effect on corticosterone metabolism and blunted intracellular action of the hormone (PubMed:17656460, PubMed:18218694). Skeletal myopathy associated with a dysregulation of the expression of proteins associated with calcium homeostasis in the sarcoplasmic reticulum and an activation of the unfolded protein response are also observed (PubMed:18222920). http://togogenome.org/gene/10090:Slc38a5 ^@ http://purl.uniprot.org/uniprot/Q3U1J0 ^@ Activity Regulation|||Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Down-regulated in Dgn3 deficient mice.|||Expressed in the ganglion cell layer and the nerve fiber layer (at protein level) (PubMed:18689705). Also expreseed in the cells of the inner nuclear layer and in the inner plexiform layer (at protein level) (PubMed:18689705). Expressed in Mueller and ganglion retinal cell (PubMed:18689705).|||Nakanishi et al (PMID:11698233) shows that the transport process is electrogenic, contrary to the conclusions of Hamdani et al (PMID:22821889) who finds that the transport is electroneutral with a Na(+):L-glutamine stoichiometry of 1:1 (By similarity). Hamdani et al. shows that this electrogenic transport describes by Nakanishi et al. would correspond to large uncoupled fluxes of protons (By similarity).|||Not inhibited by lithium (By similarity). Partial allosteric regulation on ions sodium binding (By similarity).|||Symporter that cotransports neutral amino acids and sodium ions, coupled to an H(+) antiporter activity (PubMed:15489334, PubMed:16249471). Releases L-glutamine and glycine from astroglial cells and may participate in the glutamate/GABA-L-glutamine cycle and the NMDA receptors activation (By similarity). In addition, contributes significantly to L-glutamine uptake in retina, namely in ganglion and Mueller cells therefore, participates in the retinal glutamate-glutamine cycle (PubMed:15489334, PubMed:16249471). The transport activity is pH sensitive, Li(+) tolerant, bidirectional and associated with large uncoupled fluxes of protons (By similarity). Moreover functions in both direction and is associated with large uncoupled fluxes of protons (By similarity). The transport is electroneutral coupled to the cotransport of 1 Na(+) and the antiport of 1 H(+) (By similarity). May have a particular importance for modulation of net hepatic glutamine flux (By similarity). http://togogenome.org/gene/10090:Dph2 ^@ http://purl.uniprot.org/uniprot/Q9CR25 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the DPH1/DPH2 family. DPH2 subfamily.|||Binds 1 [4Fe-4S] cluster per subunit. The cluster facilitates the reduction of the catalytic iron-sulfur cluster in the DPH1 subunit.|||Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase (By similarity). Interacts with DPH1 (PubMed:15485916, PubMed:21203470).|||Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:15485916). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit (By similarity). http://togogenome.org/gene/10090:Rbis ^@ http://purl.uniprot.org/uniprot/Q0VG62 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with the pre-60S ribosomal particles.|||Trans-acting factor in ribosome biogenesis required for efficient 40S and 60S subunit production.|||nucleolus http://togogenome.org/gene/10090:Kcnk5 ^@ http://purl.uniprot.org/uniprot/Q9JK62 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Membrane http://togogenome.org/gene/10090:C4b ^@ http://purl.uniprot.org/uniprot/P01029 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ C4 is a major histocompatibility complex class-III protein.|||Circulates in blood as a disulfide-linked trimer of an alpha, beta and gamma chain.|||Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. Catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens (By similarity).|||Prior to secretion, the single-chain precursor is enzymatically cleaved to yield non-identical chains alpha, beta and gamma. During activation, the alpha chain is cleaved by C1 into C4a and C4b, and C4b stays linked to the beta and gamma chains. Further degradation of C4b by C1 into the inactive fragments C4c and C4d blocks the generation of C3 convertase.|||Secreted|||Synapse|||axon|||dendrite http://togogenome.org/gene/10090:Glra3 ^@ http://purl.uniprot.org/uniprot/G5E811|||http://purl.uniprot.org/uniprot/Q91XP5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA3 sub-subfamily.|||Cell membrane|||Detected in brainstem, also in neurons that control rhythmic breathing (PubMed:20978350). Detected in superficial laminae of the dorsal horn of the thoracic spinal cord (PubMed:15131310). Detected in dentate gyrus in hippocampus, especially in stratum granulare (PubMed:19723286). Detected in the inner plexiform layer in the retina (at protein level) (PubMed:12975813). Detected in midbrain, thalamus, brain cortex, hippocampus, and at lower levels in cerebellum (PubMed:19723286).|||Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:15131310, PubMed:20978350). Channel characteristics depend on the subunit composition; heteropentameric channels display faster channel closure (By similarity). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents (PubMed:15131310). Contributes to increased pain perception in response to increased prostaglandin E2 levels (PubMed:15131310). Plays a role in the regulation of breathing rhythm, especially of the duration of the postinspiratory phase (PubMed:20978350). Plays a role in cellular responses to ethanol (By similarity).|||Homopentamer (in vitro) (By similarity). Heteropentamer composed of GLRA3 and GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different (By similarity).|||Inhibited by prostaglandin E2, probably via PKA-mediated phosphorylation at Ser-379 (PubMed:15131310).|||Membrane|||Mutant mice are born at the expected Mendelian rate, appear normal and are fertile. They do not display notable alterations in motor coordination and startle response, or other neuromotor defects. Glycinergic postsynaptic inhibitory currents in spinal cord appear unchanged, but are not inhibited by prostaglandin E2, contrary to what is observed with wild-type. Basal nociception is unchanged, but contrary to wild-type, mutant mice do not display increased sensitivity to pain after prostaglandin E2 injection. Likewise, they show a more rapid decrease of the increased pain sensitivity caused by agents that cause local inflammation, such as subcutaneous zymosan injection (PubMed:15131310). Mutant mice display altered phrenic nerve activity, resulting in an irregular breathing rhythm that affects especially the duration of the postinspiratory phase. Contrary to wild-type, their respiratory rhythm is not accelerated by serotonin (PubMed:20978350).|||Perikaryon|||Phosphorylated by PKA; this causes down-regulation of channel activity. Dephosphorylated in response to activation of HTR1A signaling; this increases channel activity (PubMed:20978350).|||Postsynaptic cell membrane|||Synapse|||Synaptic cell membrane|||The N-terminal domain carries structural determinants essential for agonist and antagonist binding. The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. The cytoplasmic loop is an important determinant of channel inactivation kinetics.|||The alpha subunit binds strychnine.|||dendrite http://togogenome.org/gene/10090:Rab5c ^@ http://purl.uniprot.org/uniprot/P35278 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Early endosome membrane|||Interacts with EEA1 and INCA1 (By similarity). Interacts with GDI1, GDI2, CHML and CHM; phosphorylation at Ser-85 disrupts this interaction (By similarity).|||Melanosome|||Phosphorylation of Ser-85 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||Protein transport. Probably involved in vesicular traffic.|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. http://togogenome.org/gene/10090:Ncaph ^@ http://purl.uniprot.org/uniprot/Q8C156 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CND2 (condensin subunit 2) family.|||Chromosome|||Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: NCAPH/BRRN1, NCAPD2/CAPD2 and NCAPG.|||Cytoplasm|||Nucleus|||Phosphorylated by CDK1. Its phosphorylation, as well as that of NCAPD2 and NCAPG subunits, activates the condensin complex and is required for chromosome condensation (By similarity).|||Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size. http://togogenome.org/gene/10090:Ubp1 ^@ http://purl.uniprot.org/uniprot/Q811S7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the grh/CP2 family. CP2 subfamily.|||Functions as a transcriptional activator in a promoter context-dependent manner. Involved in regulation of the alpha-globin gene in erythroid cells. Activation of the alpha-globin promoter in erythroid cells is via synergistic interaction with TFCP2. Functions as a trans-acting factor that regulates the domestic strain CYP2D9 gene through specific association with the regulatory element SDI-A1. Binding to SDI-A1 depends on the type of nucleotide at position 299; binding is abolished by a nucleotide substitution at this position. Modulates the placental expression of CYP11A1 (By similarity).|||Interacts with TFCP2 and PIAS1, and is probably part of a complex containing TFCP2, UBP1 and PIAS1.|||Nucleus|||Present in both domestic and wild mouse strains. Recognizes the genetic difference at position 299 in the SDI-A1 element.|||Ubiquitous. Highly expressed in erythroid cells. http://togogenome.org/gene/10090:Epn3 ^@ http://purl.uniprot.org/uniprot/Q91W69 ^@ Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the epsin family.|||In keratinocytes, by wounding or contact with collagen.|||cell cortex|||clathrin-coated vesicle|||perinuclear region http://togogenome.org/gene/10090:Cyth1 ^@ http://purl.uniprot.org/uniprot/Q9QX11 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoinhibited by its C-terminal basic region.|||Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate.|||Cell membrane|||Expressed in colon and small intestine (at protein level).|||Interacts with TRIM23 and CYTIP (By similarity). Interacts (via coiled-coil domain) with FRMD4A (via coiled-coil domain)(PubMed:20080746). Interacts with FRMD4B (PubMed:20080746). Found in a complex with PARD3, CYTH1 and FRMD4A (PubMed:20080746). Interacts (via N-terminal domain) with INAVA (via N-terminal domain) (By similarity).|||Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6 (PubMed:18042453, PubMed:20080746). Promotes the activation of ARF factors through replacement of GDP with GTP (PubMed:18042453). Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization, through regulation of ARF6 activity (PubMed:20080746, PubMed:29420262).|||Ubiquitinated by SCF(FBXW11) E3 ubiquitin-protein ligase complex. Ubiquitination induces proteasomal degradation.|||adherens junction|||cytosol|||tight junction http://togogenome.org/gene/10090:Abhd4 ^@ http://purl.uniprot.org/uniprot/Q8VD66 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.|||Highest levels in the CNS and in testis, intermediate levels in liver and kidney. Hardly detectable in heart.|||Homozygous knockout ABHD4 mice are born at the expected Mendelian frequency, are viable and healthy, and show no overt differences in their cage behavior compared to that of wild-type littermates.|||Lysophospholipase selective for N-acyl phosphatidylethanolamine (NAPE). Contributes to the biosynthesis of N-acyl ethanolamines, including the endocannabinoid anandamide by hydrolyzing the sn-1 and sn-2 acyl chains from N-acyl phosphatidylethanolamine (NAPE) generating glycerophospho-N-acyl ethanolamine (GP-NAE), an intermediate for N-acyl ethanolamine biosynthesis (PubMed:16818490, PubMed:25853435). Hydrolyzes substrates bearing saturated, monounsaturated, polyunsaturated N-acyl chains (PubMed:16818490, PubMed:25853435). Shows no significant activity towards other lysophospholipids, including lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylserine (PubMed:16818490).|||Thr-291 is present instead of the conserved His which is expected to be an active site residue. http://togogenome.org/gene/10090:Dpy19l3 ^@ http://purl.uniprot.org/uniprot/Q71B07 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the dpy-19 family.|||Membrane|||Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins. http://togogenome.org/gene/10090:Ireb2 ^@ http://purl.uniprot.org/uniprot/Q811J3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aconitase/IPM isomerase family.|||Binds 1 [4Fe-4S] cluster per subunit. [4Fe-4S]-binding affects RNA-binding activity, thereby inhibiting activity of the protein.|||Cytoplasm|||Interacts with RBCK1 only in iron-rich conditions. Interacts (when associated with the 4Fe-4S) with FBXL5 (By similarity). Interacts with CIAO1 and CIAO2A (PubMed:23891004).|||RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.|||Ubiquitinated and degraded by the proteasome in presence of high level of iron and oxygen. Ubiquitinated by a SCF complex containing FBXL5. Upon iron and oxygen depletion FBXL5 is degraded, preventing ubiquitination and allowing its RNA-binding activity (By similarity). http://togogenome.org/gene/10090:Gspt2 ^@ http://purl.uniprot.org/uniprot/Q149F3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Barely detectable at 15 dpc, increased after birth to reach a maximum at P15.|||Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. ERF3 subfamily.|||Component of the eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and ERF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP (PubMed:12354098). Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (By similarity). Interacts with UPF1 and PABPC1 (By similarity).|||Cytoplasm|||GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA (PubMed:12354098). GSPT2/ERF3B mediates ETF1/ERF1 delivery to stop codons: The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site (By similarity). GTP hydrolysis by GSPT2/ERF3B induces a conformational change that leads to its dissociation, permitting ETF1/ERF1 to accommodate fully in the A-site (By similarity). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (By similarity).|||Highly expressed in brain. Moderately expressed in spleen and lung. Weakly expressed in heart, liver and kidney. Expression during the cell-cycle progression is constant. http://togogenome.org/gene/10090:Dmac2l ^@ http://purl.uniprot.org/uniprot/Q9CRA7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP synthase subunit s family.|||Homotetramer. Associates with ATP synthase.|||Involved in regulation of mitochondrial membrane ATP synthase. Necessary for H(+) conduction of ATP synthase. Facilitates energy-driven catalysis of ATP synthesis by blocking a proton leak through an alternative proton exit pathway.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Xpnpep1 ^@ http://purl.uniprot.org/uniprot/Q3UE92|||http://purl.uniprot.org/uniprot/Q3UKF5|||http://purl.uniprot.org/uniprot/Q6P1B1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M24B family.|||Binds 2 manganese ions per subunit.|||Homodimer.|||Metalloaminopeptidase that catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro. Contributes to the degradation of bradykinin.|||cytosol http://togogenome.org/gene/10090:Or5k14 ^@ http://purl.uniprot.org/uniprot/E9Q7W1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbln2 ^@ http://purl.uniprot.org/uniprot/P37889|||http://purl.uniprot.org/uniprot/Q3TGL4 ^@ Caution|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibulin family.|||Component of both basement membranes and other connective tissues.|||Glucocorticoids suppressed mRNA expression and protein synthesis.|||Homotrimer; disulfide-linked. Interacts with LAMA2 (PubMed:10022829). Interacts with FBN1 (via N-terminal domain). Forms a ternary complex with ELN and FBN1 (By similarity).|||Its binding to fibronectin and some other ligands is calcium dependent. May act as an adapter that mediates the interaction between FBN1 and ELN.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||The differential expression of the fibulin family contributes to the formation of molecularly distinct extracellular matrices already during early developmental stages of a large number of tissues.|||extracellular matrix http://togogenome.org/gene/10090:Ube2q1 ^@ http://purl.uniprot.org/uniprot/Q7TSS2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated in vitro in the presence of NEDD4L.|||Belongs to the ubiquitin-conjugating enzyme family.|||Catalyzes the covalent attachment of ubiquitin to other proteins (By similarity). Involved in female fertility and embryo implantation (PubMed:23108111). May be involved in hormonal homeostasis in females (PubMed:23108111). Involved in regulation of B4GALT1 cell surface expression, B4GALT1-mediated cell adhesion to laminin and embryoid body formation (PubMed:18511602).|||Expressed in liver, brain, heart, spleen, lung, kidney, muscle, ovary, epididymis, testis and placenta (PubMed:23108111). Also expressed in thymus and ES cells (PubMed:18511602). Only expressed in the uterus during pregnancy (PubMed:23108111). Expressed in oocytes and during subsequent embryonic development stages (4-cell stage, blastocyst, 8.5 dpc, 13.5 dpc, 16.5 dpc and 18.5 dpc) (PubMed:23108111).|||Monomer and homodimer. Only the homodimer is linked to ubiquitin through thiolester activation. Interacts (via N-terminus) with B4GALT1 (via N-terminal cytoplasmic domain); the interaction is direct.|||No reproductive defects in males but females have reduced litter size due to embryo implantation failure, normal ovulation but a longer estrus cycle, reduced levels of serum prolactin at the beginning of lactation, abnormal sexual behavior and show reduced offspring care.|||Nucleus|||cytosol|||filopodium http://togogenome.org/gene/10090:Ciart ^@ http://purl.uniprot.org/uniprot/Q3TQ03 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Expression in the liver oscillates in a circadian manner with highest levels at Zeitgeber time (ZT) 12 hours (at protein level). Expression in the heart, lung, stomach and kidney oscillate in a circadian manner with highest levels at approximately circadian time (CT) 12 hours. Its expression levels peak at circadian time 12 hours (CT12), 8 hours earlier than the peak of PER1/2 and CRY1/2 transcriptional repressors (peak CT20-CT24). Thus, it can repress the CLOCK-BMAL1 activity in a different time window compared to CRY and PER proteins.|||Interacts with BMAL1, PER2, CRY2, BHLHE41, HDAC1 NR3C1.|||Mice exhibit a longer circadian period of locomotor activity, alteration in the expression of core clock genes and impairment of the response of the circadian clock to stress. The peaks of DBP, NR1D1 and PER1 gene expression persists longer in the liver between Zeitgeber times (ZT) 12-14 hours.|||Nucleus|||PML body|||Transcriptional repressor which forms a negative regulatory component of the circadian clock and acts independently of the circadian transcriptional repressors: CRY1, CRY2 and BHLHE41. In a histone deacetylase-dependent manner represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Abrogates the interaction of BMAL1 with the transcriptional coactivator CREBBP and can repress the histone acetyl-transferase activity of the CLOCK-BMAL1 heterodimer, reducing histone acetylation of its target genes. Rhythmically binds the E-box elements (5'-CACGTG-3') on circadian gene promoters and its occupancy shows circadian oscillation antiphasic to BMAL1. Interacts with the glucocorticoid receptor (NR3C1) and contributes to the repressive function in the glucocorticoid response. http://togogenome.org/gene/10090:C1ql1 ^@ http://purl.uniprot.org/uniprot/O88992 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brainstem. More abundant in areas of the nervous system involved in motor function, such as the Purkinje cells of the cerebellum, the accessory olivary nucleus, the pons and the red nucleus.|||Interacts with ADGRB3 (PubMed:21262840). Forms heterooligomers with C1QL4, when proteins are coexpressed; this interaction does not occur after secretion (PubMed:23449976).|||May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses.|||Secreted http://togogenome.org/gene/10090:Gm20927 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Slc7a9 ^@ http://purl.uniprot.org/uniprot/Q3UQE3|||http://purl.uniprot.org/uniprot/Q9QXA6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1 (PubMed:10588648) (By similarity). Has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids (By similarity). Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine (By similarity). Required for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in renal proximal tubules (By similarity).|||Belongs to the amino acid-polyamine-organocation (APC) superfamily.|||Disulfide-linked heterodimer composed of the catalytic light chain subunit SLC7A9 and the heavy chain subunit SLC3A1. The heterodimer is the minimal functional unit. Assembles in heterotetramers (dimers of heterodimers) and higher order oligomers; the oligomerization is mediated by SLC3A1 likely to prevent degradation and facilitate heteromer trafficking to the plasma membrane (By similarity) (PubMed:10588648). Interacts with CAV1 (By similarity).|||Expressed in the brush border membrane in the kidney (at protein level).|||Membrane http://togogenome.org/gene/10090:Taf1c ^@ http://purl.uniprot.org/uniprot/Q6PDZ2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with MYC and RRN3. Interacts with p53/TP53; the interaction prevents the association of SL1/TIF-IB with UBTF and represses RNA polymerase I transcription (By similarity).|||Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits. Recruits RNA polymerase I to the rRNA gene promoter via interaction with RRN3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Bpifa2 ^@ http://purl.uniprot.org/uniprot/P07743 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BPI/LBP/Plunc superfamily. Plunc family.|||Expressed at low levels at day 3 after birth but increased gradually with age from this time.|||Has strong antibacterial activity against P. aeruginosa.|||Predominates in the parotid glands, present in smaller amounts (1/10) in the submaxillary glands and in the sublingual glands, and at lower amount in the pancreas but undetectable in the liver. Found also in lacrimal gland.|||Secreted http://togogenome.org/gene/10090:Slc7a7 ^@ http://purl.uniprot.org/uniprot/Q9Z1K8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A mouse model for human lysinuric protein intolerance (LPI), where homozygous knockout mice for Slc7a7 gene are born at a frequency lower than the expected Mendelian ratio (PubMed:17376816). Only two homozygous mice survived, whereas 16 of them died within 24 hours of birth (PubMed:17376816). Growth retardation is an ongoing feature of the two surviving mice kept on a low-protein diet with citrulline supplementation. After a planned withdrawal of the special diet both mice show an acute metabolic derangement, identical to that found in human LPI, leading to death of both animals after severe hyperammonemic neurological symptoms (PubMed:17376816). Tamoxifen-inducible Slc7a7 homozygous knockout mice model resembles the human LPI phenotype, including malabsorption and impaired reabsorption of cationic amino acid (CAA), hypoargininemia and hyperammonemia. Mice also develops pulmonar alveolar proteinosis (PAP) and neurological impairment (PubMed:31653080).|||Basolateral cell membrane|||Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.|||Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.|||Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids from inside the cells in exchange with neutral amino acids plus sodium ions and may participate in nitric oxide synthesis via the transport of L-arginine (PubMed:9878049). Also mediates L-arginine transport in non-polarized cells, such as monocytes, and is essential for the correct function of these cells (By similarity). The transport mechanism is electroneutral and operates with a stoichiometry of 1:1 (By similarity). In vitro, Na(+) and Li(+), but also H(+), are cotransported with the neutral amino acids (By similarity).|||Strongly expressed in kidney and intestine. Weaker expression observed in epididymis, testis, ovary, thyroid pancreas, sub-gland and liver. http://togogenome.org/gene/10090:Tspan3 ^@ http://purl.uniprot.org/uniprot/Q545L1|||http://purl.uniprot.org/uniprot/Q80XR4|||http://purl.uniprot.org/uniprot/Q9QY33 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Interacts with claudin-11/CLDN11 and integrins.|||Membrane|||Regulates the proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair. http://togogenome.org/gene/10090:Uhrf2 ^@ http://purl.uniprot.org/uniprot/Q7TMI3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autosumoylated.|||Chromosome|||Deletion mice are viable, fertile, and grossly normal (PubMed:28402695, PubMed:28115522). However, adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain (PubMed:28402695). In addition, they display reduced 5-hydroxymethylcytosine (5hmC) in genomic DNA in the brain together with impaired spatial memory acquisition and retention (PubMed:28115522).|||E3 ligase activity is robustly activated by 5-hydroxy-methylcytosine.|||E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair. Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (PubMed:23434322, PubMed:28402695). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (PubMed:28115522). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thus inducing G1 arrest. Ubiquitinates also PCNP leading to its degradation by the proteasome. Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation. Promotes also DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation. Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation (By similarity).|||Homodimer; disulfide-linked. Binds methylated CpG containing oligonucleotides. Interacts with H3; the interaction has a preference for the 'Lys-9' trimethylated form of H3 (H3K9me3) (By similarity). Interacts with PCNP. Interacts with HDAC1. Interacts directly with CCNE1; the interaction ubiquitinates CCNE1 and appears independent of CCNE1 phosphorylation. Interacts with CCND1; the interaction ubiquitinates CCND1 and appears independent of CCND1 phosphorylation. Interacts with p53/TP53 and RB1. Interacts with UBE2I. Interacts with ZNF618. Interacts with UHRF1. Interacts with FANCD2. Interacts with ATR. Interacts with PCNA (By similarity).|||May be autoubiquitinated; which may lead to proteasomal degradation.|||Mostly detected in several tissues, including the thymus, spleen, lung, adrenal gland, and ovary. In addition, found in several tissues in the brain (cerebellum, hippocampus, and cerebral cortex).|||Nucleus|||Phosphorylated. Phosphorylation may be mediated by CDK2 (By similarity).|||Up-regulated during cell differentiation. http://togogenome.org/gene/10090:Marchf1 ^@ http://purl.uniprot.org/uniprot/Q6NZQ8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation ^@ Cytoplasmic vesicle membrane|||E3 ubiquitin-protein ligase that mediates ubiquitination of TFRC, CD86, FAS and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. By constitutively ubiquitinating MHC class II proteins in immature dendritic cells, down-regulates their cell surface localization thus sequestering them in the intracellular endosomal system.|||Early endosome membrane|||Has a short half-life. Instability/short half-life permits rapid changes that allow efficient induction of antigen presentation once antigen presenting cells, APCs, receive maturation signals. Small changes in protein levels significantly alter the cell surface display of MHC class II proteins.|||Late endosome membrane|||Lysosome membrane|||Shows increase in the cell surface expression or half-life of MHC class II. Null cells have accumulated MHC class II and CD86 at the cell surface and a low antigen-presenting ability for exogenous antigens, in conventional dendritic cells (PubMed:19917682). Null cells have high antigen-presenting ability for exogenous antigens in B-cells (PubMed:17255932).|||The RING-CH-type zinc finger domain is required for E3 ligase activity.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Vkorc1 ^@ http://purl.uniprot.org/uniprot/Q9CRC0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the VKOR family.|||Detected in liver.|||Endoplasmic reticulum membrane|||Inhibited by warfarin (coumadin) (PubMed:15879509). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity).|||Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.|||Mice are born at the expected Mendelian rate and appear normal, but die between one and twenty days after birth, due to severe bleeding. In about 75% of the cases, subdural bleeding is observed, in addition to intracerebral and intramuscular bleeding. Daily oral administration of vitamin K to the mutant mice leads to normal survival, but the mice die within seven days after the cessation of vitamin K administration. Besides, both homozygous and heterozygous mutant mice display defects in bone development with reduced length of the calcified part of the long bones in front and hind limbs.|||Partially oxidized VKORC1 forms a cysteine adduct with substrates, vitamin K 2,3-epoxide, inducing a closed conformation, juxtaposing all cysteines (S-S or SH) for unimpeded electron transfer. VKOR becomes fully oxidized with an open conformation that releases reaction products, vitamin K quinone, or hydroquinone. Cys-132 and Cys-135 constitute the catalytic redox-active center. Cys-43 and Cys-51 are the cysteine pair that mediates transfer of reducing equivalents during catalysis. http://togogenome.org/gene/10090:S100a4 ^@ http://purl.uniprot.org/uniprot/P07091|||http://purl.uniprot.org/uniprot/Q545V2 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the S-100 family.|||Calcium-binding protein that plays a role in various cellular processes including motility, angiogenesis, cell differentiation, apoptosis, and autophagy (PubMed:20519440). Increases cell motility and invasiveness by interacting with non-muscle myosin heavy chain (NMMHC) IIA/MYH9 (PubMed:8051043). Mechanistically, promotes filament depolymerization and increases the amount of soluble myosin-IIA, resulting in the formation of stable protrusions facilitating chemotaxis (PubMed:8051043). Modulates also the pro-apoptotic function of TP53 by binding to its C-terminal transactivation domain within the nucleus and reducing its protein levels (By similarity). Within the extracellular space, stimulates cytokine production including granulocyte colony-stimulating factor and CCL24 from T-lymphocytes (PubMed:20103644). In addition, stimulates T-lymphocyte chemotaxis by acting as a chemoattractant complex with PGLYRP1 that promotes lymphocyte migration via CCR5 and CXCR3 receptors (By similarity).|||Cytoplasm|||Deletion mice are fertile, grow normally and exhibit no overt abnormalities; however loss of S100A4 results in impaired recruitment of macrophages to sites of inflammation in vivo (PubMed:20519440). Mice also show decreased metastatic burden in lungs of PyMT-induced mammary tumors which is associated with reduced vessel density (PubMed:20103644).|||Homodimer. Interacts with PPFIBP1 in a calcium-dependent mode. Interacts with PGLYRP1; this complex acts as a chemoattractant that promotes lymphocyte movement. Interacts with MYH9; this interaction increases cell motility. Interacts with Annexin 2/ANXA2. Interacts with TP53; this interaction promotes TP53 degradation. Interacts with CCR5 and CXCR3. Interacts with FCGR3A; this interaction inhibits PKC-dependent phosphorylation of FCGR3A.|||Nucleus|||Secreted|||Specifically expressed in different metastatic cells.|||The mRNA coding for this protein increases in abundance after serum stimulation of quiescent mouse fibroblasts. http://togogenome.org/gene/10090:Scn4b ^@ http://purl.uniprot.org/uniprot/Q7M729 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sodium channel auxiliary subunit SCN4B (TC 8.A.17) family.|||Cell membrane|||Contains an interchain disulfide bond with SCN2A.|||Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the susceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom (By similarity).|||N-glycosylated.|||The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit (SCN2A) regulated by one or more beta subunits (SCN1B, SCN2B, SCN3B and SCN4B). SCN1B and SCN3B are non-covalently associated with SCN2A. SCN2B and SCN4B are disulfide-linked to SCN2A (By similarity). http://togogenome.org/gene/10090:Pde7a ^@ http://purl.uniprot.org/uniprot/P70453|||http://purl.uniprot.org/uniprot/Q3U3Y7|||http://purl.uniprot.org/uniprot/Q6P5G2 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE7 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.|||Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:11027622). May have a role in muscle signal transduction (By similarity).|||Interacts with CBFA2T3.|||Widely expressed with highest levels in the skeletal muscle.|||cytosol http://togogenome.org/gene/10090:Aebp1 ^@ http://purl.uniprot.org/uniprot/Q640N1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although related to peptidase M14 family, lacks the active site residues and zinc-binding sites, suggesting that it has no carboxypeptidase activity.|||As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix.|||Belongs to the peptidase M14 family.|||By TGF-beta. Expression is also induced by a high fat diet.|||Cytoplasm|||Expressed in the somites and dorsa from 9.5 dpc and in the yolk sac and embryonic vasculature from 10.5 dpc. Expression within the large and small blood vessels increases at 11.5 dpc and 13.5 dpc, with high expression in the vascular smooth muscle at 16.5 dpc. Also expressed later in development in mesenchymal cells in the dermal layer, the developing skeleton, connective tissue and the umbilical ring and vessels. Up-regulated during vascular smooth muscle cell differentiation and down-regulated during adipocyte differentiation and osteoblast differentiation.|||Isoform 1 and isoform 2 are expressed in adipose tissue, brain, heart, kidney, liver, lung, skeletal muscle, small intestine, spleen and testis. Isoform 2 is expressed in macrophages. Expressed in aorta, preadipocytes, adipocyte tissue, brain, heart, liver, lung, skeletal muscle, skin and spleen (at protein level).|||Isoform 1: Interacts with different types of collagen, including collagens I, III, and V (By similarity). Isoform 2: Interacts with GNG5, NFKBIA, MAPK1, MAPK3 and PTEN. Interaction with MAPK1 may stimulate DNA-binding. May interact with calmodulin. Binds to DNA in vitro.|||May positively regulate MAP-kinase activity in adipocytes, leading to enhanced adipocyte proliferation and reduced adipocyte differentiation. May also positively regulate NF-kappa-B activity in macrophages by promoting the phosphorylation and subsequent degradation of I-kappa-B-alpha (NFKBIA), leading to enhanced macrophage inflammatory responsiveness. Can act as a transcriptional repressor.|||Nucleus|||Phosphorylated by MAPK1 in vitro.|||Secreted|||The F5/8 type C domain binds to different types of collagen, including collagens I, III, and V.|||Two independent knockout mice have been generated for the gene encoding this protein, and these exhibit different phenotypes. Mice lacking exons 7-12 exhibit reduced growth rate and body weight and resistance to dietary-induced obesity. Individual adipocytes from these animals are hypoproliferative while the adipose tissue is prone to apoptosis. Mice lacking exons 7-16 die perinatally from gastroschisis, in which abdominal viscera are extruded through the ventral body wall. Surviving mice exhibit deficient wound healing, having dermal fibroblasts with reduced proliferative capacity. Mice lacking exons 7-16 may exhibit phenotypes arising from effects on the locus encoding Pold2, which lies immediately downstream of this locus. http://togogenome.org/gene/10090:Eya3 ^@ http://purl.uniprot.org/uniprot/P97480|||http://purl.uniprot.org/uniprot/Q3TP96|||http://purl.uniprot.org/uniprot/Q6P4T3 ^@ Caution|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:14628042 also shows serine/threonine protein phosphatase activity.|||Belongs to the HAD-like hydrolase superfamily. EYA family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Expressed in branchial arches, CNS and developing eye.|||Interacts with SIX1 and DACH1, and probably SIX2, SIX4 and SIX5.|||Nucleus|||Ser-203 phosphorylation is required for localization at sites of DNA damage and directing interaction with H2AX.|||Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (By similarity). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. The phosphatase activity has been shown in vitro. Coactivates SIX1. Seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity. May be involved in development of the eye. May play a role in mediating the induction and differentiation of cranial placodes. http://togogenome.org/gene/10090:Cand1 ^@ http://purl.uniprot.org/uniprot/Q6ZQ38 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAND family.|||Cytoplasm|||Interacts with TBP (By similarity). Part of a complex that contains CUL1 and RBX1. Interacts with unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5. Does not bind neddylated CUL1. Interaction with cullins is abolished in presence of COMMD1, which antagonizes with CAND1 for interacting with cullins. Interacts with ERCC6 (By similarity). Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions are bridged by cullins and strongly inhibits the neddylation of cullins (By similarity).|||Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or11g2 ^@ http://purl.uniprot.org/uniprot/Q7TRM0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gata6 ^@ http://purl.uniprot.org/uniprot/Q61169 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in myocardium, vascular smooth muscle, gut epithelium, and osteoclasts.|||Interacts with LMCD1.|||Nucleus|||Produced by alternative initiation at Met-147 of isoform 1.|||The GATA-type zinc fingers mediate interaction with LMCD1.|||Transcriptional activator that regulates SEMA3C and PLXNA2 (PubMed:19666519). May regulate genes that protect epithelial cells from bacterial infection (By similarity). Involved in gene regulation specifically in the gastric epithelium (By similarity). Involved in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343). Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (PubMed:15329343). http://togogenome.org/gene/10090:Car6 ^@ http://purl.uniprot.org/uniprot/P18761|||http://purl.uniprot.org/uniprot/Q3TTT1|||http://purl.uniprot.org/uniprot/Q3V197 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-carbonic anhydrase family.|||Major constituent of saliva.|||Reversible hydration of carbon dioxide. Its role in saliva is unknown.|||Secreted http://togogenome.org/gene/10090:Cdk5r1 ^@ http://purl.uniprot.org/uniprot/P61809|||http://purl.uniprot.org/uniprot/Q542T9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin-dependent kinase 5 activator family.|||Brain and neuron specific.|||Cell membrane|||Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3 (PubMed:11882646). Only the heterodimer shows kinase activity (PubMed:11882646). Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4 (PubMed:17143272). Interacts with RASGRF2. The complex p35/CDK5 interacts with CLOCK (PubMed:24235147).|||Heterodimer of a catalytic subunit and a regulatory subunit.|||Membrane|||Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35 (By similarity).|||Nucleus|||Perikaryon|||Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis.|||The p35 form is proteolytically cleaved by calpain, giving rise to the p25 form. P35 has a 5 to 10 fold shorter half-life compared to p25. The conversion results in deregulation of the CDK5 kinase: p25/CDK5 kinase displays an increased and altered tau phosphorylation in comparison to the p35/CDK5 kinase in vivo.|||Ubiquitinated, leading to its degradation: degradation of p35 by proteasome results in down-regulation of CDK5 activity. During this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Ubiquitinated by the CRL2(FEM1B) complex, which recognizes the -Gly-Leu-Asp-Arg C-degron at the C-terminus, leading to its degradation.|||neuron projection|||p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-BMAL1 heterodimer in association with altered stability and subcellular distribution.|||perinuclear region http://togogenome.org/gene/10090:Krt31 ^@ http://purl.uniprot.org/uniprot/Q61765 ^@ Miscellaneous|||Similarity ^@ Belongs to the intermediate filament family.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Chrdl2 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1E8|||http://purl.uniprot.org/uniprot/D3YV59|||http://purl.uniprot.org/uniprot/Q8VEA6 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:14660436 interacts with human BMP2, BMP4, BMP5, BMP6, BMP7 but not human INHBA. According to PubMed:15094188 interacts with human INHBA but not human BMP2, BMP4 and BMP6.|||Implicated in tumor angiogenesis (By similarity). May inhibits BMPs activity by blocking their interaction with their receptors. Has a negative regulator effect on the cartilage formation/regeneration from immature mesenchymal cells, by preventing or reducing the rate of matrix accumulation. May play a role during myoblast and osteoblast differentiation, and maturation.|||In embryo expressed to the surface chondrocytes of developing joint cartilage and to the connective tissue of reproductive organs.|||Interacts with GDF5. May interact with INHBA, BMP2, BMP4, BMP5, BMP6, and BMP7.|||Secreted|||Weakly expressed in the liver and kidney. In reproductive organs expressed in connective tissues such as ligaments of the ovary and oviduct in females, and of testis, epididymis and certain male accessory sex glands in males. Expression was high in uterine myometrium. Weakly expressed in cartilage of the femoral head, patella, articular facets of vertebrae, in the annulus fibrosus of intervertebral disks. In normal cartilage, expression was confined to articular chondrocytes especially in the superficial zone. http://togogenome.org/gene/10090:Csgalnact2 ^@ http://purl.uniprot.org/uniprot/Q8C1F4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Golgi stack membrane|||Transfers 1,4-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of glucuronic acid (GlcUA). Required for addition of the first GalNAc to the core tetrasaccharide linker and for elongation of chondroitin chains (By similarity). http://togogenome.org/gene/10090:Or10al7 ^@ http://purl.uniprot.org/uniprot/Q7TRI9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:B3gntl1 ^@ http://purl.uniprot.org/uniprot/Q3U129 ^@ Function|||Similarity ^@ Belongs to the glycosyltransferase 2 family.|||Putative glycosyltransferase. http://togogenome.org/gene/10090:Or6z3 ^@ http://purl.uniprot.org/uniprot/Q8VGH5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm20852 ^@ http://purl.uniprot.org/uniprot/Q5M8R5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Gm13272 ^@ http://purl.uniprot.org/uniprot/B1AYI3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Mslnl ^@ http://purl.uniprot.org/uniprot/Q8C160 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mesothelin family.|||May play a role in cellular adhesion.|||Membrane http://togogenome.org/gene/10090:Slc25a23 ^@ http://purl.uniprot.org/uniprot/Q6GQS1 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport.|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Electroneutral antiporter that mediates the transport of adenine nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenine nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenine nucleotide-dependent metabolic pathways. Also acts as a regulator of mitochondrial calcium uptake and can probably transport trace amounts of other divalent metal cations in complex with ATP. In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides.|||Interacts with MCU. Interacts with MICU1.|||Linker region/H9 could directly block the transport of substrates across the transporter.|||Mitochondrion inner membrane|||The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity.|||The regulatory N-terminal domain/NTD, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity. http://togogenome.org/gene/10090:Ctso ^@ http://purl.uniprot.org/uniprot/Q4QQL3|||http://purl.uniprot.org/uniprot/Q8BM88 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C1 family.|||Lysosome|||Proteolytic enzyme possibly involved in normal cellular protein degradation and turnover. http://togogenome.org/gene/10090:Fbxo45 ^@ http://purl.uniprot.org/uniprot/Q8K3B1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FBXO45/Fsn family.|||Component of E3 ubiquitin ligase complex consisting of FBXO45, MYCBP2 and SKP1. Functions in substrate recognition but plays also an important role in assembly of the complex (By similarity). Required for normal neuromuscular synaptogenesis, axon pathfinding and neuronal migration (PubMed:32341084). Regulates neuron migration during brain development through interaction with N-cadherin/CDH2 after secretion via a non-classical mechanism (By similarity). Plays a role in the regulation of neurotransmission at mature neurons (By similarity). May control synaptic activity by controlling UNC13A via ubiquitin dependent pathway (By similarity). Specifically recognizes TP73, promoting its ubiquitination and degradation. Polyubiquitinates NMNAT2, an adenylyltransferase that acts as an axon maintenance factor, and regulates its stability and degradation by the proteasome. Acts also by ubiquitinating FBXW7 during prolonged mitotic arrest and promotes FBXW7 proteasomal degradation. Induces subsequently an increase in mitotic slippage and prevents mitotic cell death. In response to influenza infection, mediates interferon-lambda receptor IFNLR1 polyubiquitination and degradation through the ubiquitin-proteasome system by docking with its intracellular receptor domain (By similarity).|||Expressed speciffically in the central nervous system, including cerebellum, medulla oblongata, olfactory bulb, hippocampus, cortex and brain stem.|||Forms a complex with MYCBP2 and SKP1 (PubMed:19398581). Interacts with HEY1; leading to FBXO45 nuclear translocation. Interacts (via SPRY domain) with CDH2.|||Homozygous animals die soon after birth due to respiratory distress. Embryos show abnormal innervation of the diaphragm, impaired synapse formation at neuromuscular junctions, and aberrant development of axon fiber tracts in the brain.|||Nucleus|||Postsynaptic cell membrane|||Presynaptic cell membrane|||Secreted http://togogenome.org/gene/10090:Decr1 ^@ http://purl.uniprot.org/uniprot/Q9CQ62 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxiliary enzyme of beta-oxidation. It participates in the metabolism of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in mitochondria. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.|||Homotetramer.|||Mitochondrion http://togogenome.org/gene/10090:Cbr2 ^@ http://purl.uniprot.org/uniprot/P08074 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||By glucocorticoids. Activated by fatty acids.|||Homotetramer.|||May function in the pulmonary metabolism of endogenous carbonyl compounds, such as aliphatic aldehydes and ketones derived from lipid peroxidation, 3-ketosteroids and fatty aldehydes, as well as in xenobiotic metabolism.|||Mitochondrion matrix|||Predominantly expressed in lung, in ciliated cells, non-ciliated bronchiolar cells and type-II alveolar pneumocytes (PubMed:7705352, PubMed:8040004). Also detected in adipose tissue (at protein level) (PubMed:7705352). Low expression in testis, heart, kidney, spleen, brain and liver (PubMed:7705352).|||Uses both NADP and NAD as substrates. Has a strong preference for NADP. http://togogenome.org/gene/10090:Tbc1d14 ^@ http://purl.uniprot.org/uniprot/Q8CGA2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with ULK1. May interact with RAB11A and RAB11B, but does not exhibit any GTPase-activating activity toward these proteins. Interacts with TRAPPC8.|||Plays a role in the regulation of starvation-induced autophagosome formation. Together with the TRAPPIII complex, regulates a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.|||cis-Golgi network|||trans-Golgi network http://togogenome.org/gene/10090:Ttc41 ^@ http://purl.uniprot.org/uniprot/Q692V3 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in lung and myeloid leukemia cell line (at protein level). Isoform 4: expressed in heart (at protein level). http://togogenome.org/gene/10090:Cep19 ^@ http://purl.uniprot.org/uniprot/Q9CQA8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP19 family.|||Interacts with CEP43; this interaction is required for its localization to the mother centriole. Interacts (via residues 121-150) with RABL2B. Interacts (via C-terminus) with CEP350; this interaction is required for its localization to the mother centriole.|||Required for ciliation. Recruits the RABL2B GTPase to the ciliary base to initiate ciliation. After specifically capturing the activated GTP-bound RABL2B, the CEP19-RABL2B complex binds intraflagellar transport (IFT) complex B from the large pool pre-docked at the base of the cilium and thus triggers its entry into the cilia. Involved in the early steps in cilia formation by recruiting the ciliary vesicles (CVs) to the distal end of the mother centriole where they fuse to initiate cilium assembly. Involved in microtubule (MT) anchoring at centrosomes.|||Severe obesity, hyperphagia, decreased energy expenditure, impaired whole-body fat oxidation, altered hepatic insulin signaling, and impaired glucose and insulin tolerance. Spermatogenic cells and seminiferous tubules show marked degeneration.|||centriole|||cilium basal body|||spindle pole http://togogenome.org/gene/10090:Mgat5 ^@ http://purl.uniprot.org/uniprot/Q059T5|||http://purl.uniprot.org/uniprot/Q8R4G6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A secreted form is released from the membrane after cleavage by gamma-secretase.|||Belongs to the glycosyltransferase 18 family.|||Catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides (PubMed:10700233, PubMed:14561752, PubMed:22715095). Catalyzes an important step in the biosynthesis of branched, complex-type N-glycans, such as those found on EGFR, TGFR (TGF-beta receptor) and CDH2 (PubMed:12122020, PubMed:10700233, PubMed:14561752, PubMed:15459394, PubMed:22715095). Via its role in the biosynthesis of complex N-glycans, plays an important role in the activation of cellular signaling pathways, reorganization of the actin cytoskeleton, cell-cell adhesion and cell migration (PubMed:10700233, PubMed:14561752, PubMed:15459394). MGAT5-dependent EGFR N-glycosylation enhances the interaction between EGFR and LGALS3 and thereby prevents rapid EGFR endocytosis and prolongs EGFR signaling (PubMed:15459394). Required for efficient interaction between TGFB1 and its receptor (PubMed:15459394). Enhances activation of intracellular signaling pathways by several types of growth factors, including FGF2, PDGF, IGF, TGFB1 and EGF (PubMed:15459394). MGAT5-dependent CDH2 N-glycosylation inhibits CDH2-mediated homotypic cell-cell adhesion and contributes to the regulation of downstream signaling pathways (PubMed:14561752). Promotes cell migration (PubMed:14561752, PubMed:15459394). Contributes to the regulation of the inflammatory response (PubMed:11217864, PubMed:15459394). MGAT5-dependent TCR N-glycosylation enhances the interaction between TCR and LGALS3, limits agonist-induced TCR clustering, and thereby dampens TCR-mediated responses to antigens (PubMed:11217864). Required for normal leukocyte evasation and accumulation at sites of inflammation (PubMed:15459394). Inhibits attachment of monocytes to the vascular endothelium and subsequent monocyte diapedesis (By similarity).|||Detected in cerebellum.|||Golgi apparatus membrane|||Membrane|||Mice are born at the expected Mendelian rate and have no visible phenotype at birth. Adult mice display abnormal leukocyte recruitment to inflamed tissues, hypersensitivity of T cells to agonists that activate T cell receptors, an age-related decrease in the cellularity of kidney glomeruli and a tendency to develop proliferative glomerulonephritis, plus defective nurturing behavior (PubMed:10700233, PubMed:11217864). Mutant mice show increased responsiveness to treatments that cause delayed-type hypersensitivity (PubMed:11217864). Mice show increased incidence of autoimmune encephalomyelitis in response to injections with MBP (PubMed:11217864). Transgenic mice that express polyomavirus middle T antigen develop mammary tumors; 50% of female wild-type mice have detectable tumors after 16 weeks, but it takes 24 weeks until 50% of the female mice that lack Mgat5 develop mammary tumors. Male mice that express polyomavirus middle T antigen develop mammary tumors after 6 to 9 months; males that lack Mgat5 develop tumors after 10 to 13 months. Formation of lung metastases is about 5% of wild-type (PubMed:10700233). Tumor initiation is not decreased in mice that lack Mgat5, but tumor growth is strongly decreased (PubMed:10700233). Tumor cells from mutant mice show impaired membrane ruffling, probably due to decreased activation of phosphoinositide-3-kinase (PI3K) (PubMed:10700233). Embryonic fibroblasts from Mgat5-deficient mice display increased Cdh2-mediated cell-cell adhesion (PubMed:14561752). Mutant mice that lack both Mgat5 and Mgat5b display no visible changes in brain anatomy, but their brains display defective biosynthesis of both O-mannosyl glycans and N-linked glycans (PubMed:22715095).|||N-glycosylated.|||Perikaryon|||Promotes proliferation of umbilical vein endothelial cells and angiogenesis, at least in part by promoting the release of the growth factor FGF2 from the extracellular matrix.|||Secreted http://togogenome.org/gene/10090:Mbd1 ^@ http://purl.uniprot.org/uniprot/Q9Z2E2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Highly expressed in kidney, liver and brain. Detected at lower levels in heart, lung, skeletal muscle, spleen and testis.|||Interacts with OASL, ATF7IP, ATF7IP2 and BAHD1. Binds CHAF1A and the SUV39H1-CBX5 complex via the MBD domain. Binds MGP via the TRD domain. May be part of the MeCP1 complex. During DNA replication, it recruits SETDB1 to form a S phase-specific complex that facilitates methylation of H3 'Lys-9' during replication-coupled chromatin assembly and is at least composed of the CAF-1 subunit CHAF1A, MBD1 and SETDB1 (By similarity).|||Interacts with the Ten-1 ICD form of TENM1.|||Nucleus|||Nucleus matrix|||Nucleus speckle|||Sumoylated, sumoylation may increase interaction with ATF7IP.|||The methyl-CpG-binding domain (MBD) functions both in binding to methylated DNA and in protein interactions.|||The third CXXC-type zinc finger mediates binding to DNA containing unmethylated CpG dinucleotides.|||The transcriptional repression domain (TRD) is involved in transcription repression and in protein interactions.|||Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binding is abolished by the presence of 7-mG that is produced by DNA damage by methylmethanesulfonate (MMS). Acts as transcriptional repressor and plays a role in gene silencing by recruiting ATF7IP, which in turn recruits factors such as the histone methyltransferase SETDB1. Probably forms a complex with SETDB1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Isoform 1 can also repress transcription from unmethylated promoters. http://togogenome.org/gene/10090:Itch ^@ http://purl.uniprot.org/uniprot/Q8C863 ^@ Activity Regulation|||Caution|||Disease Annotation|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with Epstein-Barr virus LMP2A.|||Activated by NDFIP1- and NDFIP2-binding (PubMed:25632008). Activated by PI4K2A-binding (By similarity). Inhibited by DTX3L-binding (By similarity). Inhibited by N4BP1 binding (PubMed:17592138).|||Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:15358865, PubMed:16446428, PubMed:17592138, PubMed:18628966, PubMed:20392206, PubMed:25632008). It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (By similarity). Involved in the control of inflammatory signaling pathways (By similarity). Is an essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (By similarity). Promotes the association of the complex after TNF stimulation (By similarity). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (By similarity). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (By similarity). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (By similarity). Regulates the transcriptional activity of several transcription factors involved in immune response (PubMed:15358865, PubMed:11828324). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (By similarity). Mediates JUN ubiquitination and degradation (PubMed:15358865). Mediates JUNB ubiquitination and degradation (PubMed:11828324, PubMed:15358865). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (PubMed:11828324). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (By similarity). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (By similarity). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (By similarity). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (By similarity). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (By similarity). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:18628966). Ubiquitinates SNX9 (By similarity). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (PubMed:25632008). Involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP (By similarity). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (By similarity). Ubiquitinates NEDD9/HEF1, resulting in proteasomal degradation of NEDD9/HEF1 (By similarity).|||Cell membrane|||Cytoplasm|||Defects in Itch are the cause of the itchy phenotype which is an inflammatory and immunological condition characterized by inflammation in the lung and stomach, hyperplasia in lymphoid and hematopoietic cells and constant itching in the skin.|||Detected in uterus (at protein level) (PubMed:23146885). Widely expressed (PubMed:9462742).|||Early endosome membrane|||Endosome membrane|||It is uncertain whether Met-1 or Met-11 is the initiator.|||Major form.|||Monomer. Part of a ternary complex composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4 (via WW domains); the complex mediates ubiquitination and proteasomal degradation of NEDD9/HEF1 (By similarity). Interacts (via WW domains) with OCNL (PubMed:11782481). Interacts (via WW domains) with NOTCH1 (PubMed:10940313, PubMed:18628966). Interacts (via WW domains) JUN (PubMed:11828324). Interacts with JUNB; the interaction promotes ITCH-mediated ubiquitination and degradation of JUNB (PubMed:11828324). Interacts with FYN; the interaction phosphorylates ITCH on Tyr-381 decreasing binding of JUNB (By similarity). Interacts (via WW domain 2) with N4BP1; the interaction inhibits the E3 ubiquitin-protein ligase activity (PubMed:17592138). Interacts with NDFIP1 and NDFIP2; the interaction with NDFIP proteins activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (PubMed:11748237, PubMed:17137798, PubMed:25632008). Interacts with ARHGEF7 (By similarity). Interacts with RNF11 (By similarity). Interacts (via the WW 1 domain) with NFE2 (via the PXY motif 1); the interaction promotes 'Lys-63'-linked ubiquitination of NFE2, retains it in the cytoplasm and prevents its transactivation activity (By similarity). Interacts (via WW domains) with CXCR4 (via C-terminus); the interaction depends on CXCR4 phosphorylation (By similarity). Found in a complex with E3 ligase DTX3L and ESCRT-0 components HGS and STAM (By similarity). Interacts with DTX3L (via C-terminus); the interaction is increased upon CXCL12 stimulation and inhibits ITCH catalytic activity (the interaction is direct) (By similarity). Interacts with HGS (By similarity). Interacts (via WW domains) with PCBP2 within a complex containing ITCH, MAVS and PCBP2 (By similarity). Interacts (via WW domains) with TXNIP (via C-terminus) (By similarity). Interacts with p15 BID (PubMed:20392206). Interacts with ERBB4 (By similarity).Interacts with DTX1 (By similarity). Interacts with SPART (By similarity). Interacts with SNX9 and SNX18 (By similarity). Interacts (via its WW domains) with ATN1 (By similarity). Interacts (via WW domains) with SGK3 (By similarity). Interacts with CBLC (By similarity). Interacts with OTUD7B (By similarity). Interacts (via WW domain 1,2 and 3) with PI4K2A; the interaction inhibits PI4K2A catalytic activity and promotes ITCH catalytic activity (PubMed:23146885). Interacts with ARRDC4 (By similarity). Part of a complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts with UBE2L3; the interaction is mediated by NDFIP1 (PubMed:25632008). Interacts with MAPK8/JNK1 (PubMed:16446428). Interacts (via WW domains) with ARRDC1 (via PPxY motifs); the interaction is direct and participates in the recruitment of the ubiquitin-protein ligase ITCH to the NOTCH1 receptor (By similarity). Interacts (via WW domains) with ARRDC2 (By similarity). Interacts (via WW domains) with ARRDC3 (By similarity). Interacts directly with LDLRAD3; this interaction promotes ITCH auto-ubiquitination leading to its degradation (PubMed:26854353). Interacts with ENTREP1; enhances the ubiquitination of CXCR4 by ITCH and its subsequent endocytosis (By similarity).|||Monoubiquitinated. Autopolyubiquitinated with 'Lys-63' linkages which does not lead to protein degradation.|||Nucleus|||On T-cell activation, phosphorylation by the JNK cascade on serine and threonine residues surrounding the PRR domain accelerates the ubiquitination and degradation of JUN and JUNB. The increased ITCH catalytic activity due to phosphorylation by JNK1 may occur due to a conformational change disrupting the interaction between the PRR/WW motifs domain and the HECT domain and, thus exposing the HECT domain. Phosphorylation by FYN reduces interaction with JUNB and negatively controls JUN ubiquitination and degradation. Interacts directly with LDLRAD3; this interaction promotes ITCH auto-ubiquitination leading to its degradation (PubMed:26854353).|||The WW domain 4 mediates interaction with ENTREP1.|||The WW domains mediate interaction with PPxY motif-containing proteins. http://togogenome.org/gene/10090:Vmn2r85 ^@ http://purl.uniprot.org/uniprot/G3UW56 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Epb41l1 ^@ http://purl.uniprot.org/uniprot/Q9Z2H5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highest expression in brain, also present in kidney, olfactory epithelium, retina, sensory ganglia, gastrointestinal tract (only enteric neurons) and lung.|||Interacts with AGAP2.|||May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases.|||cytoskeleton http://togogenome.org/gene/10090:Tet1 ^@ http://purl.uniprot.org/uniprot/Q3URK3 ^@ Caution|||Cofactor|||Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TET family.|||Binds 1 Fe(2+) ion per subunit.|||Binds 3 zinc ions per subunit. The zinc ions have a structural role.|||Chromosome|||Dioxygenase that plays a key role in active DNA demethylation (PubMed:27916660, PubMed:36056023). As isoform 1, binds to promoters, particularly to those with high CG content, however displays reduced global chromatin affinity compared with isoform 1, leading to decreased global DNA demethylation compared with isoform 1 (PubMed:27916660). Contrary to isoform 1, isoform 2 localizes during S phase to sites of ongoing DNA replication in heterochromatin, causing a significant de novo 5hmC formation, globally, and more so in heterochromatin, including LINE 1 interspersed DNA repeats leading to their activation (PubMed:36056023). In hippocampal neurons, isoform 2 regulates the expression of a unique subset of genes compared with isoform 1, although some overlap between both isoforms, hence differentially regulating excitatory synaptic transmission (PubMed:33262245). In hippocampal neuron cell cultures, isoform 2 controls miniature excitatory postsynaptic current frequency, but not amplitude (PubMed:33262245). Isoform 2 may regulate genes involved in hippocampal-dependent memory, leading to negative regulation of memory, contrary to isoform 1 that may improve memory (PubMed:33262245). In immature and partially differentiated gonadotrope cells, represses luteinizing hormone gene LHB expression directly and does not catalyze 5hmC at the gene promoter (PubMed:28855337).|||Dioxygenase that plays a key role in active DNA demethylation (PubMed:27916660, PubMed:36056023). Binds to promoters, particularly to those with high CG content (PubMed:27916660). In hippocampal neurons, isoform 1 regulates the expression of a unique subset of genes compared to isoform 2, although some overlap between both isoforms, hence differentially regulates excitatory synaptic transmission (PubMed:33262245). In hippocampal neuron cell cultures, isoform 1 controls both miniature excitatory postsynaptic current amplitude and frequency (PubMed:33262245). Isoform 1 may regulate genes involved in hippocampal-dependent memory, leading to positive regulation of memory, contrary to isoform 2 that may decrease memory (PubMed:33262245).|||Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) (PubMed:20639862, PubMed:21496894, PubMed:21778364). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression (PubMed:28504700, PubMed:32286661). Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, iron homeostasis, neural activity or DNA repair (PubMed:31089182, PubMed:32855402, PubMed:33895792, PubMed:20639862). Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification (PubMed:28504700, PubMed:20639862). Together with QSER1, plays an essential role in the protection and maintenance of transcriptional and developmental programs to inhibit the binding of DNMT3A/3B and therefore de novo methylation (By similarity). May play a role in the pancreatic beta-cell specification during development. In this context, may function as an upstream epigenetic regulator of PAX4 presumably through direct recruitment by FOXA2 to a PAX4 enhancer to preserve its unmethylated status, thereby potentiating PAX4 expression to adopt beta-cell fate during endocrine lineage commitment (By similarity). Under DNA hypomethylation conditions, such as in female meiotic germ cells, may induce epigenetic reprogramming of pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions. PCH forms chromocenters in the interphase nucleus and chromocenters cluster at the prophase of meiosis. In this context, may also be essential for chromocenter clustering in a catalytic activity-independent manner, possibly through the recruitment polycomb repressive complex 1 (PRC1) to the chromocenters (PubMed:34166371). During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation (PubMed:23151479). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By similarity).|||Down-regulated in response to hippocampal neuron stimulation, whereas isoform 1 transcript levels are unaffected (PubMed:33262245). Down-regulated by GNRH1 in pituitary cells from immature animals (PubMed:28855337). Down-regulated by gonadal steroids, including estradiol E2 and dihydrotestosterone DHT, in gonadotrope cells from immature animals (PubMed:28855337).|||During development, a switch between isoforms 1 and 2 regulates DNA demethylation, imprint erasure and gene regulation. The switch may be controlled by alternative promoters. Isoform 2 is hardly detectable in early embryos until 14.5 dpc, although some expression is seen in the brain already at 10.5 dpc, and is predominantly expressed in most adult tissues (PubMed:27916660, PubMed:28531272). In cultured embryonic stem cells, during differentiation into neurons, isoform 2 is undetectable during the first 7 days and then progressively increases (PubMed:27916660). Expressed in gonadotropic cells, with considerably higher levels in immature cells from 6 day old mice in which the gonadotrope population is expanding, than in the gonadotropic cells of adult, sexually mature animals (PubMed:28855337).|||During development, a switch between isoforms 1 and 2 regulates epigenetic memory erasure. The switch is controlled by alternative promoters (PubMed:27916660, PubMed:28531272). Isoform 1 is expressed from the one-cell stage embryos until 14.5 dpc and is hardly detectable in most adult tissues (PubMed:20639862, PubMed:27916660, PubMed:28531272). At the blastocyst stage, enriched in the inner cell mass (at protein level) (PubMed:20639862). In cultured embryonic stem cells, during differentiation into neurons, highly expressed during the first 2 days. Expression then decreases until day 9 when the levels become hardly detectable and at which point expression of isoform 2 progressively increases (PubMed:27916660).|||Expressed at high levels in germinal vesicle (GV) stage and MII-stage oocytes. Expression levels increase following fertilization and reach a peak at the 4-cell stage and decrease in morula and blastula (PubMed:24357321). During embryonic development, preferentially expressed in primordial germ cells, where strong expression is already detected at 10.5 dpc, a peak of expression is reached at 12.5 dpc, followed by a decrease, until 16.5 dpc. Compared to primordial germ cells, low expression levels are observed in somatic cells starting from 9.5 dpc with a slow increase until 16.5 dpc (PubMed:23151479).|||Expressed in germinal vesicle (GV) stage and MII-stage oocytes and in early embryos (PubMed:24357321). Also detected somatic tissues, including brain, liver and kidney, but at very low levels (PubMed:24357321).|||Glycosylated. Interaction with OGT leads to GlcNAcylation.|||Interacts with SIN3A; recruits the transcriptional co-repressor SIN3A to gene promoters (PubMed:21490601). Interacts with HCFC1 (PubMed:23352454). Interacts (via C-terminus) with OGT (PubMed:23352454, PubMed:27916660). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (PubMed:28554894). Interacts with QSER1 (By similarity). Interacts with NONO (via DNA-binding domain); this interaction recruits TET1 to genomic loci (PubMed:32286661). Interacts with FOXA2; this interaction may recruit TET1 to specific enhancers to preserve their unmethylated status and hence allowing gene expression (By similarity). Interacts with RNF2 (PubMed:34166371). Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex (By similarity).|||Interacts with UHRF1; this interaction induces the recruitment of TET1 to replicating heterochromatin (PubMed:36056023). Interacts with DCAF1 (PubMed:36056023).|||Monoubiquitinated by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex.|||Monoubiquitinated by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.|||No visible phenotype; mice are viable, fertile and grossly normal, although some mice have a slightly smaller body size at birth. Embryonic stem cells (ESCs) have reduced levels of 5-hydroxymethylcytosine (5hmC) and slight changes in global gene expression, but are pluripotent and support development. However, knockout mice have an altered response to iron overload (PubMed:33895792). In a different experimental setting, the number of viable knockout homozygous animals was shown to be only approximately one-third of the amount expected due to embryonic lethality (PubMed:23151479). In this setting, in female embryos, the size of the ovaries is smaller, with a reduced number of oocytes from 16.5 to 18.5 dpc, probably due to severely impaired meiotic progression and increased apoptosis (PubMed:23151479). Mice lacking both Tet1 and Tet2 are fertile, with females having smaller ovaries and reduced fertility. They display decreased 5hmC and abnormal methylation at various imprinted loci. ESCs lacking both Tet1 and Tet2 remain pluripotent but lack 5hmC, leading to developmental defects in chimeric embryos (PubMed:23352810).|||Nucleus|||Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastoma genesis.|||Predominantly expressed in early embryos. Also expressed in embryonic stem cells and in primordial germ cells (PubMed:20639862, PubMed:27916660, PubMed:28504700, PubMed:28531272, PubMed:28855337). Expressed in adult tissues, including brain cortex, cerebellum, heart, kidney, liver, muscle and spleen, although at much lower levels than isoform 2 (PubMed:28531272, PubMed:28855337, PubMed:33262245). In the brain, expressed at higher levels in glial cells than in neurons (PubMed:33262245). Expressed in placenta (PubMed:28855337). Expressed in the pituitary, most probably in thyrotropes (PubMed:28855337).|||Preferentially expressed in differentiated cells, including in cerebral cortex, cerebellum and thymus (PubMed:27916660). Also expressed in heart, kidney, liver, muscle and spleen at much higher levels than isoform 1 (PubMed:28531272, PubMed:28855337, PubMed:33262245). In the brain, expressed at higher levels in neurons than in glial cells (PubMed:33262245). Expressed in the olfactory bulb and in the mammary gland (PubMed:28531272, PubMed:28855337).|||Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system (PubMed:21496894). According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG.|||The CXXC zinc finger plays a role in TET1 chromatin loading and participates in binding to CpG-DNA. However, the global chromatin binding can be mediated by the entire N-terminus and occurs even in the absence of the CXXC domain (PubMed:27916660). The zinc finger domain impedes association DNA replication sites and prevents aberrant 5mC oxidation (PubMed:36056023). http://togogenome.org/gene/10090:Bad ^@ http://purl.uniprot.org/uniprot/Q61337 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Bcl-2 family.|||Cytoplasm|||Forms heterodimers with the anti-apoptotic proteins, Bcl-X(L), Bcl-2 and Bcl-W. Also binds protein S100A10 (By similarity). The Ser-112/Ser-136 phosphorylated form binds 14-3-3 proteins. Interacts with AKT1 and PIM3 (By similarity). Interacts (via BH3 domain) with NOL3 (via CARD domain); preventing the association of BAD with BCL2 (By similarity). Interacts with HIF3A isoform 2 (via C-terminus domain); the interaction reduces the binding between BAD and BAX (PubMed:21546903). Interacts with GIMAP3/IAN4 and GIMAP5/IAN5 (PubMed:16509771).|||Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.|||Methylation at Arg-131 and Arg-133 by PRMT1 inhibits Akt-mediated phosphorylation at Ser-136.|||Mitochondrion outer membrane|||Phosphorylated on one or more of Ser-112, Ser-136, Ser-155 and Ser-170 in response to survival stimuli, which blocks its pro-apoptotic activity. Phosphorylation on Ser-136 or Ser-112 promotes heterodimerization with 14-3-3 proteins. This interaction then facilitates the phosphorylation at Ser-155, a site within the BH3 motif, leading to the release of Bcl-X(L) and the promotion of cell survival. Ser-136 is the major site of AKT/PKB phosphorylation, Ser-155 the major site of protein kinase A (CAPK) phosphorylation.|||Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2. Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.|||The protein name 'Bcl2 antagonist of cell death' may be misleading. The protein antagonises Bcl2-mediated repression of cell death, hence it promotes apoptosis. http://togogenome.org/gene/10090:Irs1 ^@ http://purl.uniprot.org/uniprot/P35569 ^@ Function|||PTM|||Subunit|||Tissue Specificity ^@ Expressed in osteoblasts, but not in osteoclasts.|||Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity). Interacts with ROCK1 (By similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7 (By similarity). Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) (By similarity). Interacts with UBTF and PIK3CA (PubMed:15197263). Interacts (via PH domain) with PHIP (PubMed:11018022). Interacts with FER (PubMed:11006284). Interacts with ALK (By similarity). Interacts with EIF2AK2/PKR (PubMed:22948222). Interacts with GKAP1 (PubMed:25586176). Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (PubMed:27739494). Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (PubMed:27739494). Interacts with SQSTM1; the interaction is disrupted by the presence of tensin TNS2 (By similarity).|||May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).|||Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-307 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity). Phosphorylation of Tyr-891 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-265, Ser-302, Ser-632 and Ser-1097 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (By similarity). Phosphorylated on tyrosine residues in response to insulin (PubMed:25586176). In skeletal muscles, dephosphorylated on Tyr-608 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (By similarity).|||Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2). http://togogenome.org/gene/10090:Ppp2r2d ^@ http://purl.uniprot.org/uniprot/F6RV17|||http://purl.uniprot.org/uniprot/Q925E7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ B regulatory subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit. The activity of PP2A complexes containing PPP2R2D (PR55-delta) fluctuate during the cell cycle: the activity is high in interphase and low in mitosis. During mitosis, activity of PP2A is inhibited via interaction with phosphorylated ENSA and ARPP19 inhibitors. Within the PP2A complexes, the B regulatory subunits modulate substrate selectivity and catalytic activity, and may also direct the localization of the catalytic enzyme to a particular subcellular compartment (By similarity).|||Belongs to the phosphatase 2A regulatory subunit B family.|||Cytoplasm|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with ENSA (when phosphorylated at 'Ser-67') and ARPP19 (when phosphorylated at 'Ser-62'), leading to inhibit PP2A activity (By similarity). Interacts with IER5 (By similarity). http://togogenome.org/gene/10090:Tas2r117 ^@ http://purl.uniprot.org/uniprot/Q7M715 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Cysltr1 ^@ http://purl.uniprot.org/uniprot/Q99JA4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||MK-571, a selective antagonist, was shown to inhibit eosinophilia, bronchial hyperreactivity and microvascular leakage. Zafirlukast (Accolate) and pranlukast (Onon) were also shown to be selective antagonists.|||Receptor for cysteinyl leukotrienes mediating constriction of the microvascular smooth muscle during an inflammatory response. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >> LTE4 = LTC4 >> LTB4.|||Widely expressed, with higher expression in the lung and skin, intermediate levels in the heart, kidney and stomach and lower levels in several other tissues. Isoform 1 is the most abundant form in all tested tissues. http://togogenome.org/gene/10090:Wdr72 ^@ http://purl.uniprot.org/uniprot/D3YYM4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasmic vesicle|||Expressed in maturation stage ameloblasts (at protein level) (PubMed:19853237, PubMed:25008349).|||Plays a major role in formation of tooth enamel (PubMed:25008349, PubMed:26247047). Specifically required during the maturation phase of amelogenesis for normal formation of the enamel matrix and clearance of enamel proteins (PubMed:25008349, PubMed:26247047). May be involved in localization of the calcium transporter SLC24A4 to the ameloblast cell membrane (PubMed:26247047).|||Viable with no gross morpholgical defects (PubMed:25008349, PubMed:26247047). At 6-7 weeks of age teeth have an opaque, chalky appearance, with reduced enamel thickness at occlusal surfaces (PubMed:25008349, PubMed:26247047). Body weight is reduced, probably due to problems with chewing hard foods (PubMed:25008349). Enamel formation is abnormal from the maturation stage onwards with significantly reduced mineral density and retention of proteinaceous material in the enamel matrix (PubMed:25008349, PubMed:26247047). Tooth enamel hardness is ten times lower than wild type (PubMed:26247047). Attachment of ameloblasts to the enamel layer may be weakened (PubMed:26247047). The calcium transporter SLC24A4 fails to localize to the distal ameloblast membrane (PubMed:26247047). In maturation stage ameloblasts expression levels of amelogenin appear to be reduced, although abnormally high amelogenin levels are found in the extracellular enamel matrix (PubMed:25008349, PubMed:26247047). http://togogenome.org/gene/10090:Trerf1 ^@ http://purl.uniprot.org/uniprot/Q8BXJ2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15.5 dpc, highly expressed in brain, lung, adrenal, thymus and kidney. Expression was also seen in spinal cord, retina and snout.|||Binds DNA and activates transcription of CYP11A1. Interaction with CREBBP and EP300 results in a synergistic transcriptional activation of CYP11A1.|||Highly expressed in kidney, lung and brain. In the brain, expression was seen in the basal ganglia, hippocampus, piriform cortex, cerebral cortex, ventromedial nucleus of the hypothalamus and the dorsal and superior central nuclei of the raphe.|||Interacts with CREBBP and EP300. Interacts with DNTTIP1 and DNTT.|||Nucleus http://togogenome.org/gene/10090:Mafa ^@ http://purl.uniprot.org/uniprot/Q8CF90 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. Maf subfamily.|||Expressed in brain, lung, spleen, pancreas and kidney (PubMed:12368292, PubMed:14680841). In the pancreas, expressed in the insulin-producing beta-cells of the islets of Langerhans (at protein level) (PubMed:12917329, PubMed:15923615). Also expressed in the eye (PubMed:12368292, PubMed:15923615).|||Forms homodimers (By similarity). Interacts with NEUROD1 and PDX1 (PubMed:15665000). May interact with MAFB, FOS, JUN and PCAF (By similarity).|||In the developing pancreas, expressed exclusively in the insulin-positive cells from 13.5 dpc onward and never in the glucagon-expressing cells (at protein level) (PubMed:14973194). At 12.5dpc, at the mRNA level, detected in each formed somite, in myotomal cells. Also detected in the head neural tube, liver cells and, at low levels, in some mesenchyme-like cells (PubMed:14680841).|||Mice are born at the expected Mendelian rate and survive until adulthood. They show a normal pancreatic morphology at birth. A 12 weeks, they exhibit a reduction in the proportion of Langerhans islet beta-cells and impaired glucose-stimulated insulin secretion and eventually they develop diabetes mellitus.|||Nucleus|||Phosphorylated at tyrosines.|||Transcriptional factor that activates insulin gene expression (PubMed:12368292, PubMed:15665000). Acts synergistically with NEUROD1/BETA2 and PDX1 (PubMed:15665000). Binds the insulin enhancer C1/RIPE3b element (PubMed:12917329, PubMed:14680841, PubMed:14973194, PubMed:15665000). Binds to consensus TRE-type MARE 5'-TGCTGACTCAGCA-3' DNA sequence (By similarity).|||Ubiquitinated, leading to its degradation by the proteasome.|||Up-regulated by glucose in pancreatic beta-cell lines. http://togogenome.org/gene/10090:Runx1t1 ^@ http://purl.uniprot.org/uniprot/B1AXH8|||http://purl.uniprot.org/uniprot/B1AXH9|||http://purl.uniprot.org/uniprot/Q3UQX8|||http://purl.uniprot.org/uniprot/Q61909|||http://purl.uniprot.org/uniprot/Q8C066 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CBFA2T family.|||Homotetramer (By similarity). Heterotetramer with CBFA2T2 and CBFA2T3 (By similarity). Interacts with TCF12, SIN3A, HDAC1, HDAC2, HDAC3, NCOR1 and NCOR2. Interacts with ATN1 (via its N-terminus); the interaction enhances the transcriptional repression (By similarity).|||Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure.|||Nucleus|||The TAFH domain mediates interaction with transcription regulators.|||Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Can repress the expression of MMP7 in a ZBTB33-dependent manner. Can repress transactivation mediated by TCF12 (By similarity). Acts as a negative regulator of adipogenesis (PubMed:23527555). http://togogenome.org/gene/10090:Reep6 ^@ http://purl.uniprot.org/uniprot/Q9JM62 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DP1 family.|||Endoplasmic reticulum membrane|||Expressed in the inner segment of rod photoreceptors and outer plexiform layer of the retina (at protein level) (PubMed:24691551, PubMed:28369466, PubMed:28475715). Expressed in liver, but not detected in brain, muscle, kidney, retinal cone photoreceptors or retinal ganglion cells (at protein level) (PubMed:24691551). Highly expressed in the ganglion cell layer of the retina and in liver, and also detected at low levels in kidney and testis (PubMed:15728532). Isoform 1: Expressed in the retina (PubMed:15728532, PubMed:24691551). Isoform 2: Expressed in liver (PubMed:24691551).|||Interacts with STX3 (PubMed:28369466). Interacts with clathrin (PubMed:28369466).|||Isoform 1 shows increasing levels of expression in the retina from birth, reaching maximal levels by 12 days of age.|||Required for correct function and survival of retinal photoreceptors (PubMed:24098485, PubMed:24691551, PubMed:28475715). Required for retinal development (PubMed:28369466). In rod photoreceptors, facilitates stability and/or trafficking of guanylate cyclases and is required to maintain endoplasmic reticulum and mitochondrial homeostasis (PubMed:28475715). May play a role in clathrin-coated intracellular vesicle trafficking of proteins from the endoplasmic reticulum to the retinal rod plasma membrane (PubMed:24098485, PubMed:28369466).|||Viable, however mice develop progressive deterioration in retinal response, and male mice are sterile (PubMed:28369466, PubMed:28475715). Progressive retinal rod dysfunction first evident from one month of age progressing to almost undetectable scotopic response at one year of age (PubMed:28369466). Progressive degeneration of photopic response by retinal cone receptors first evident at one year of age (PubMed:28369466). Defective retinal morphology with significant thinning of the outer nuclear layer and reduced rows of nuclei (PubMed:28369466, PubMed:28475715). Accumulation of vacuole-like structures at the apical inner segment of the retina (PubMed:28369466). Reduced and disorganised photoreceptors with shortened fragmented outer segment (PubMed:28475715). Altered endoplasmic reticulum (ER) organization with increased ER area near the base of the outer segment, increased number of mitochondria in the rod ellipsoid region and induction of ER stress (PubMed:28475715). Reduced retinal expression of phototransduction proteins Cngb1 and Gnat1 and of Aipl1 (PubMed:28369466). Reduced expression of guanylate cyclases Gucy2e/GC1 and Gucy2f/GC2 in the rod outer segment and mislocalization of Pde6a from the outer segment to the inner segment and outer nuclear layer (PubMed:28475715).|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Amhr2 ^@ http://purl.uniprot.org/uniprot/Q8K592 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Interacts with type I receptor ACVR1.|||Membrane|||On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for anti-Muellerian hormone. http://togogenome.org/gene/10090:Hyou1 ^@ http://purl.uniprot.org/uniprot/Q9JKR6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 70 family.|||Endoplasmic reticulum lumen|||Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. May play a role as a molecular chaperone and participate in protein folding (By similarity).|||Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. http://togogenome.org/gene/10090:Guf1 ^@ http://purl.uniprot.org/uniprot/Q8C3X4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. LepA subfamily.|||Mitochondrion inner membrane|||Promotes mitochondrial protein synthesis. May act as a fidelity factor of the translation reaction, by catalyzing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Binds to mitochondrial ribosomes in a GTP-dependent manner. http://togogenome.org/gene/10090:Mfsd1 ^@ http://purl.uniprot.org/uniprot/Q9DC37 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ After 24 hours of starvation, up-regulated in the brainstem and down-regulated in the cortex and striatum (PubMed:27981419). Following 8 weeks of high-fat diet, down-regulated in brainstem and hypothalamus (PubMed:27981419).|||Belongs to the major facilitator superfamily.|||Homodimer (PubMed:32959924). Interacts with lysosomal protein GLMP (via lumenal domain); the interaction starts while both proteins are still in the endoplasmic reticulum and is required for stability and lysosomal localization of MFSD1 (PubMed:31661432, PubMed:32959924).|||In brain, expressed in the cortex, striatum hippocampus, hypothalamus, thalamus and brainstem (at protein level) (PubMed:27981419). Widely expressed with highest levels in kidney and spleen (at protein level) (PubMed:31661432).|||Lysosomal transporter which is essential for liver homeostasis (PubMed:31661432). Required to maintain stability and lysosomal localization of GLMP (PubMed:31661432, PubMed:32959924).|||Lysosome membrane|||Not N-glycosylated.|||Splenomegaly and development of severe liver disease characterized by extravasation of erythrocytes, sinusoidal damage, loss of liver sinusoidal endothelial cells (LSECs) and fibrosis (PubMed:31661432). Normal life span but there is a significantly higher occurrence of liver tumors in old animals of more than 1.5 years of age (PubMed:31661432). Significantly reduced levels of Glmp (PubMed:31661432, PubMed:32959924). Conditional knockout in LSECs results in a tuberous liver appearance (PubMed:31661432).|||The dileucine internalization motif is required for lysosomal localization. http://togogenome.org/gene/10090:Vsig1 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1E9|||http://purl.uniprot.org/uniprot/Q9D2J4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Abcc1 ^@ http://purl.uniprot.org/uniprot/A5D6P3|||http://purl.uniprot.org/uniprot/O35379 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Cell membrane|||Homozygous ABCC1 knockout mice are healthy and fertile up to at least 12 months of age. They are hypersensitive to anticancer drugs resulting in an increased loss of body weight and mortality and have a decreased inflammatory response.|||MK 571 inhibits sphingosine 1-phosphate and leukotriene C4 export.|||Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595, PubMed:9359705). Hydrolyzes ATP with low efficiency. Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (By similarity). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (PubMed:9359705). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769).|||Membrane http://togogenome.org/gene/10090:Aggf1 ^@ http://purl.uniprot.org/uniprot/Q7TN31 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with the secreted angiogenic factor TNFSF12.|||Promotes angiogenesis and the proliferation of endothelial cells. Able to bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion (By similarity).|||Secreted http://togogenome.org/gene/10090:Or6c5 ^@ http://purl.uniprot.org/uniprot/Q7TRI5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Entr1 ^@ http://purl.uniprot.org/uniprot/A2AIW0|||http://purl.uniprot.org/uniprot/A2AIW3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ENTR1 family.|||Cytoplasm|||Early endosome|||Endosome|||Endosome-associated protein that plays a role in membrane receptor sorting, cytokinesis and ciliogenesis. Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Involved in the regulation of cytokinesis; the function may involve PTPN13 and GIT1. Plays a role in the formation of cilia. Involved in cargo protein localization, such as PKD2, at primary cilia (By similarity). Involved in the presentation of the tumor necrosis factor (TNF) receptor TNFRSF1A on the cell surface, and hence in the modulation of the TNF-induced apoptosis (PubMed:16332174).|||Found in a complex with ENTR1, PTPN13 and GIT1. Interacts with PTPN13 (via the FERM domain) (By similarity). Interacts (via N-terminus) with GIT1 (via N- and C-terminus); this interaction is direct (PubMed:23108400). Interacts with NOD2. Interacts (via N-terminus) with IFT88. Interacts with VPS35.|||May be involved in modulation of TNF response. May be involved in presentation of TNFRSF1A on the cell surface (PubMed:16332174). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Involved in the regulation of cytokinesis; the function may involve PTPN13 and GIT1 (By similarity).|||Midbody|||Phosphorylated.|||Recycling endosome|||Tne N-terminal domain is necessary and sufficient for basal body localization and ciliogenesis.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Capza1 ^@ http://purl.uniprot.org/uniprot/Q5RKN9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the F-actin-capping protein alpha subunit family.|||F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.|||Heterodimer of an alpha and a beta subunit. http://togogenome.org/gene/10090:Ubxn2b ^@ http://purl.uniprot.org/uniprot/Q0KL01 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein required for Golgi and endoplasmic reticulum biogenesis. Involved in Golgi and endoplasmic reticulum maintenance during interphase and in their reassembly at the end of mitosis. The complex formed with VCP has membrane fusion activity; membrane fusion activity requires USO1-GOLGA2 tethering and BET1L. VCPIP1 is also required, but not its deubiquitinating activity. Together with NSFL1C/p47, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase. Also, regulates spindle orientation during mitosis.|||Belongs to the NSFL1C family.|||Endoplasmic reticulum|||Golgi apparatus|||Interacts with VCP. Does not bind ubiquitin.|||Nucleus|||centrosome|||cytosol http://togogenome.org/gene/10090:Snai2 ^@ http://purl.uniprot.org/uniprot/P97469 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snail C2H2-type zinc-finger protein family.|||Cytoplasm|||GSK3B-mediated phosphorylation results in cytoplasmic localization and degradation.|||Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains). Interacts (via zinc fingers) with KPNA2, KPNB1, and TNPO1. May interact (via zinc fingers) with IPO7 (By similarity).|||Nucleus|||Repression activity depends on the C-terminal DNA-binding zinc fingers and on the N-terminal repression domain.|||Transcriptional repressor that modulates both activator-dependent and basal transcription. Involved in the generation and migration of neural crest cells. Plays a role in mediating RAF1-induced transcriptional repression of the TJ protein, occludin (OCLN) and subsequent oncogenic transformation of epithelial cells. Represses BRCA2 expression by binding to its E2-box-containing silencer and recruiting CTBP1 and HDAC1 in breast cells. In epidermal keratinocytes, binds to the E-box in ITGA3 promoter and represses its transcription. Involved in the regulation of ITGB1 and ITGB4 expression and cell adhesion and proliferation in epidermal keratinocytes. Binds to E-box2 domain of BSG and activates its expression during TGFB1-induced epithelial-mesenchymal transition (EMT) in hepatocytes. Represses E-Cadherin/CDH1 transcription via E-box elements. Involved in osteoblast maturation. Binds to RUNX2 and SOC9 promoters and may act as a positive and negative transcription regulator, respectively, in osteoblasts. Binds to CXCL12 promoter via E-box regions in mesenchymal stem cells and osteoblasts. Plays an essential role in TWIST1-induced EMT and its ability to promote invasion and metastasis (By similarity). http://togogenome.org/gene/10090:Sdf4 ^@ http://purl.uniprot.org/uniprot/Q61112 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CREC family.|||Binds calcium, probably via its EF-hands.|||Golgi apparatus lumen|||May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.|||Ubiquitous. http://togogenome.org/gene/10090:Phgdh ^@ http://purl.uniprot.org/uniprot/Q61753 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.|||Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Does not catalyze the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate.|||Decreased level of free serine, glycine, taurine, GABA, glutamine, and threonine in spinal cord and head. Impaired central nervous system (CNS) with shorter neural tube length and overall growth retardation. Severe atrophy at the thoracic level, particularly in the dorsal spinal cord. Poorly developed dorsal horn and adjacent mantle zone. Neurons fail to develop neurites, particularly commissural axonal fibers.|||Homotetramer. http://togogenome.org/gene/10090:Fam227b ^@ http://purl.uniprot.org/uniprot/Q9D518 ^@ Sequence Caution|||Similarity ^@ Belongs to the FAM227 family.|||Intron retention. The sequence differs at its 3' end due to intron retention. http://togogenome.org/gene/10090:Tfeb ^@ http://purl.uniprot.org/uniprot/Q3UKG7|||http://purl.uniprot.org/uniprot/Q6P203|||http://purl.uniprot.org/uniprot/Q9R210 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alkylated via a non-enzymatic covalent modification (PubMed:35662396). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates Cys-211, preventing association with 14-3-3/YWHA adapters, thereby promoting nuclear translocation and activity (PubMed:35662396).|||Belongs to the MiT/TFE family.|||Death between 9.5 and 10.5 days in embryonic development (PubMed:9806910). Embryos display severe defects in placental vascularization (PubMed:9806910). The embryonic vasculature forms normally but few vessels are seen entering the placenta and those that do enter fail to thrive and branch normally (PubMed:9806910). Conditional deletion in kidney does not lead to any abnormality in the kidney (PubMed:32612235). Mice lacking Tfeb and Flcn in the kidney do not show any abnormality in the kidney, suggesting that the kidney phenotype observed in Flcn knockout mice is due to constitutive activation of Tfeb (PubMed:32612235).|||Expressed at low levels in the embryo but at high levels in the labyrinthine trophoblast cells of the placenta.|||Homodimer and heterodimer; with TFE3 or MITF (By similarity). Interacts (when phosphorylated by MTOR) with YWHAZ; promoting retention in the cytosol (By similarity). Interacts with Irgm1; promoting association between TFEB and PPP3CB and dephosphorylation (By similarity). Interacts with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD); promoting its recruitment to lysosomal membrane in the presence of nutrients (By similarity).|||Lysosome membrane|||Nucleus|||Phosphorylation at Ser-210 by MTOR via non-canonical mTORC1 pathway regulates its subcellular location and activity (By similarity). When nutrients are present, phosphorylation by MTOR promotes association with 14-3-3/YWHA adapters and retention in the cytosol (By similarity). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation by calcineurin PPP3CB and translocation to the nucleus (By similarity). Dephosphorylated by calcineurin PPP3CB in response to lysosomal Ca(2+) release (By similarity). Irgm1 promotes dephosphorylation by calcineurin PPP3CB, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (By similarity). Exported from the nucleus in a mTORC1-dependent manner in response to nutrient availability (By similarity).|||Sumoylated; does not affect dimerization with MITF.|||The leucine zipper region is essential for homo- or heterodimerization and high-affinity DNA binding. DNA binding is mediated by the basic region.|||Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:16936731, PubMed:22343943, PubMed:27278822, PubMed:35662396). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:16936731, PubMed:27278822). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:35662396). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (By similarity). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (By similarity). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (PubMed:16936731). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (By similarity). Plays a role in the signal transduction processes required for normal vascularization of the placenta (PubMed:9806910). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica (PubMed:24882217, PubMed:27184844, PubMed:35662396). Infection promotes itaconate production, leading to alkylation, resulting in nuclear localization and transcription factor activity (PubMed:35662396). Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response (PubMed:35662396).|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Hmgcl ^@ http://purl.uniprot.org/uniprot/P38060 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HMG-CoA lyase family.|||Homodimer; disulfide-linked. Can also form homotetramers.|||Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism.|||Mitochondrion matrix|||Peroxisome http://togogenome.org/gene/10090:Gm21412 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Wnk1 ^@ http://purl.uniprot.org/uniprot/P83741 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated in response to hyperosmotic stress: cell shrinkage promotes formation of a membraneless compartment that concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK (By similarity). Activation requires autophosphorylation of Ser-382 and, to a lower extent, Ser-378 (By similarity). Autophosphorylation and subsequent activation is inhibited by increases in intracellular ionic strength: Cl(-) potently inhibits WNK1 kinase activity via direct binding (By similarity). Also inhibited by K(+) ions (By similarity).|||Autophosphorylated at Ser-378 and Ser-382, promoting its activity (By similarity). Autophosphorylation at Ser-382 is inhibited by intracellular calcium (By similarity). Phosphorylation at Thr-58 increases ability to activate SGK1 (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.|||Cytoplasm|||Disordered regions undergo liquid-liquid phase separation (LLPS) for the formation of a cytoplasmic membraneless compartment that concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK.|||Embryonic lethality before day 13 of gestation (PubMed:14610273, PubMed:19644017). Embryos show cardiovascular developmental defects: the developing heart has smaller chambers and reduced myocardial trabeculation at E10.5 (PubMed:19644017). Yolk sac vessels in the E10.5 null mutant fail to remodel into a network of large and small vessels and embryonic vessels show defective angiogenesis that involves both arteries and veins (PubMed:19644017). Hypomorphic mice display a significant decrease in blood pressure (PubMed:14610273). Conditional deletion in endothelial cells leads to cardiovascular developmental defects, leading to embryonic lethality (PubMed:19644017).|||HSN2 was originally thought to be an intronless gene lying within a WNK1 gene intron. It has been shown to be a nervous system-specific exon of WNK1 included in isoform 2 and isoform 3 (PubMed:18521183).|||Interacts with WNK3. Interacts with WNK4; inhibiting the activity of WNK4 (By similarity). Interacts with SGK1; promoting its activation. Associates with the mTORC2 complex (By similarity). Interacts with UVRAG (By similarity).|||Interacts with isoform 1; inhibiting isoform 1 activity.|||It is uncertain whether Met-1 or Met-214 is the initiator.|||Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:21131289). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity).|||May be O-glycosylated.|||May be due to intron retention.|||Nucleus|||Probable cloning artifact.|||Restricted to the nervous system, expressed preferentially in sensory neurons than in motor neurons and in general more abundant in axons than in cell bodies (at protein level) (PubMed:18521183). In the DRG, predominantly expressed in the satellite cells that envelop sensory neurons, but low expression also observed in the cell bodies of neurons (at protein level) (PubMed:18521183). In the sciatic nerve, expressed in the Schwann cells that surround axons and in a mosaic distribution of axons (at protein level) (PubMed:18521183). In the spinal cord, expressed in superficial layers (LI and LII), as well as in the fibers of the Lissauer tract (at protein level) (PubMed:18521183). Also detected in the axon fibers of dorsolateral funiculus and lateral funiculus (at protein level) (PubMed:18521183).|||Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:12671053, PubMed:14610273). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (By similarity). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (By similarity). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (By similarity). Also acts as a regulator of angiogenesis in endothelial cells (PubMed:19644017). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (By similarity). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (By similarity). Acts as a negative regulator of autophagy (By similarity). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (By similarity). WNK1 may also play a role in actin cytoskeletal reorganization (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (PubMed:21317537, PubMed:23542070). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (By similarity). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (By similarity).|||The RFXV motifs mediate recognition with downstream kinases OXSR1/OSR1 and STK39/SPAK.|||Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation (By similarity). Also ubiquitinated by the BCR(KLHL2) complex (By similarity).|||Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins.|||Widely expressed in both adult and embryonic tissue, with highest levels observed in the testis and lower levels in heart, lung, kidney, placenta, brain and skeletal muscle (PubMed:11498583, PubMed:14514722, PubMed:12522152). Expressed in pancreatic duct (PubMed:21317537). Two isoforms are expressed in heart, a single shorter isoform in the kidney (PubMed:14514722). Locates to the distal convoluted tubule, the medullary collecting duct and the cortical collecting duct of the kidney (PubMed:14514722).|||spindle http://togogenome.org/gene/10090:Or13a28 ^@ http://purl.uniprot.org/uniprot/Q8VGM2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cramp1 ^@ http://purl.uniprot.org/uniprot/Q6PG95 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cramped family.|||Nucleus http://togogenome.org/gene/10090:Ceacam5 ^@ http://purl.uniprot.org/uniprot/Q3UKK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the immunoglobulin superfamily. CEA family.|||Cell membrane|||Cell surface|||Cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Mediates homophilic and heterophilic cell adhesion with other carcinoembryonic antigen-related cell adhesion molecules, such as CEACAM6. Plays a role as an oncogene by promoting tumor progression; induces resistance to anoikis of colorectal carcinoma cells.|||Homodimer. http://togogenome.org/gene/10090:Il1rl2 ^@ http://purl.uniprot.org/uniprot/Q149G7|||http://purl.uniprot.org/uniprot/Q9ERS7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the interleukin-1 receptor family.|||Complete protection from imiquimodum (IMQ)-induced skin pathology observed in wild-type mice, including hyperkeratosis, acanthosis, neutrophil recruitment, and expansion of IL-17-producing T-cells.|||Expressed in bone marrow-derived dendritic cells, splenic CD4(+) T-cells, bone marrow-derived macrophages and bone marrow-derived neutrophils.|||Interacts with IL1RAP; the association is enhanced by IL36B indicative for an functional signaling complex and inhibited by IL36RN.|||Membrane|||Receptor for interleukin-36 (IL36A, IL36B and IL36G). After binding to interleukin-36 associates with the coreceptor IL1RAP to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways. The IL-36 signaling system is thought to be present in epithelial barriers and to take part in local inflammatory response; it is similar to the IL-1 system. Seems to be involved in skin inflammatory response by induction of the IL-23/IL-17/IL-22 pathway.|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. http://togogenome.org/gene/10090:Dusp10 ^@ http://purl.uniprot.org/uniprot/Q9ESS0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Monomer. Interacts with MAPK14.|||Nucleus|||Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38. http://togogenome.org/gene/10090:Trmt61a ^@ http://purl.uniprot.org/uniprot/Q80XC2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM61 family.|||Catalytic subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA. Catalytic subunit of mRNA N(1)-methyltransferase complex, which mediates methylation of adenosine residues at the N(1) position of a small subset of mRNAs: N(1) methylation takes place in tRNA T-loop-like structures of mRNAs and is only present at low stoichiometries.|||Heterotetramer; composed of two copies of TRMT6 and two copies of TRMT61A.|||Nucleus http://togogenome.org/gene/10090:Ccr3 ^@ http://purl.uniprot.org/uniprot/P51678|||http://purl.uniprot.org/uniprot/Q3U5L7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice with induced pulmonary inflammation exhibit reduced trafficking of eosinophils from the blood into the lung parenchyma and increased numbers of intraepithelial mast cells in the trachea. Cholinergic stimulation resulted in airway hyperresponsiveness.|||Detected in skeletal muscle and in trace amounts in leukocytes.|||Membrane|||Receptor for C-C type chemokine. Binds and responds to a variety of chemokines, including CCL11, CCL26, CCL7, CCL13, RANTES(CCL5) and CCL15. Subsequently transduces a signal by increasing the intracellular calcium ions level. In addition acts as a possible functional receptor for NARS1. http://togogenome.org/gene/10090:Pcp4l1 ^@ http://purl.uniprot.org/uniprot/Q6W8Q3 ^@ Developmental Stage|||Similarity|||Tissue Specificity ^@ Belongs to the PCP4 family.|||Expressed in laminar and nuclear structures of the CNS.|||First detected at 9.5 dpc in the neural tube. Expressed at early stages of development in the isthmus and in metencephalic and mesencephalic roof plates. At later stages of development, it is expressed in structures corresponding to circumventricular organs which in adult control the production of the cerebrospinal fluid. http://togogenome.org/gene/10090:Il6 ^@ http://purl.uniprot.org/uniprot/A0A0G2JGF4|||http://purl.uniprot.org/uniprot/A2RTD1|||http://purl.uniprot.org/uniprot/P08505 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability. Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:17075861). Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:11786910). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (PubMed:28402851). Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (PubMed:11113088). Also acts as a myokine (By similarity). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (PubMed:11113088, PubMed:8910279). Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (PubMed:15124018). Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).|||Animals have normal T-cell numbers in the lamina propria but the T(H)17 cells are reduced by about 10-fold (PubMed:16990136). They develop mature-onset obesity and have disturbed carbohydrate and lipid metabolism, increased leptin levels and decreased responsiveness to leptin treatment (PubMed:11786910). Animals have impaired liver regeneration characterized by liver necrosis and failure (PubMed:8910279). Mutants infected with influenza virus do not show a significant difference on germinal center B cells compared to wild-types (PubMed:23045607). Double knockouts for IL21 and IL6 infected with influenza virus show a significant reduction in germinal centers in both the draining lymphatic nodes and the spleens to wild-types. Animals show a significant reduction in virus-specific IgM and IgG (PubMed:23045607).|||Belongs to the IL-6 superfamily.|||Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST (PubMed:28265003). Interacts with IL6R (via the N-terminal ectodomain); this interaction may be affected by IL6R-binding with SORL1, hence decreasing IL6 cis signaling. Interacts with SORL1 (via the N-terminal ectodomain); this interaction leads to IL6 internalization and lysosomal degradation. May form a trimeric complex with the soluble SORL1 ectodomain and soluble IL6R receptor; this interaction might stabilize circulating IL6, hence promoting IL6 trans signaling (PubMed:28265003).|||Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism (Probable). Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (PubMed:8910279). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (PubMed:27893700).|||Expressed by dendritic cells and macrophages (PubMed:27893700, PubMed:23045607). Expressed by activated follicular B cells (PubMed:23045607). Abundantly expressed in the central nervous system (CNS), particularly the hypothalamic region (PubMed:28402851).|||IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury. In the adaptive immune response, is required for the differentiation of B-cells into immunoglolin-secreting cells (Probable). Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Together with IL21, controls the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection (PubMed:23045607). Required to drive naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (PubMed:16990136, PubMed:27893700). Also required for proliferation of myeloma cells and the survival of plasmablast cells (Probable).|||In activated follicular B cells, expression is induced early after influenza virus infection (PubMed:23045607). Plasma levels are highly increased upon exercise, due to enhanced production by contracting skeletal muscles (PubMed:22037645).|||N- and O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Lsm4 ^@ http://purl.uniprot.org/uniprot/Q9CY46|||http://purl.uniprot.org/uniprot/Q9QXA5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the snRNP Sm proteins family.|||Binds specifically to the 3'-terminal U-tract of U6 snRNA.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome.|||LSm subunits form a heteromer with a doughnut shape.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA.|||Ubiquitous. http://togogenome.org/gene/10090:Zdhhc6 ^@ http://purl.uniprot.org/uniprot/Q9CPV7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DHHC palmitoyltransferase family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum palmitoyl acyltransferase that mediates palmitoylation of proteins such as AMFR, CALX, ITPR1 and TFRC (PubMed:25368151). Palmitoylates calnexin (CALX), which is required for its association with the ribosome-translocon complex and efficient folding of glycosylated proteins (By similarity). Mediates palmitoylation of AMFR, promoting AMFR distribution to the peripheral endoplasmic reticulum (By similarity). Together with SELENOK, palmitoylates ITPR1 in immune cells, leading to regulate ITPR1 stability and function (PubMed:25368151). Stearoyltransferase that mediates stearoylation of TFRC to inhibit TFRC-mediated activation of the JNK pathway and mitochondrial fragmentation (By similarity).|||Homooligomerizes (By similarity). Interacts with SELENOK (PubMed:25368151).|||Palmitoylated at 3 different sites by ZDHHC16. The combination of the different palmitoylation events strongly affects the quaternary assembly of ZDHHC6, its localization, stability and function. Palmitoylation at Cys-328 accelerates the turnover of ZDHHC6. Depalmitoylated by LYPLA2.|||The C-terminal di-lysine motif confers endoplasmic reticulum localization.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Slc25a48 ^@ http://purl.uniprot.org/uniprot/Q8BW66 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ido2 ^@ http://purl.uniprot.org/uniprot/Q8R0V5 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Activity is inhibited by D-1MT (1-methyl-D-tryptophan) and MTH-trp (methylthiohydantoin-DL-tryptophan) but not L-1MT (1-methyl-L-tryptophan).|||Belongs to the indoleamine 2,3-dioxygenase family.|||Binds 1 heme group per subunit.|||Catalyzes the first and rate-limiting step in the kynurenine pathway of tryptophan catabolism (PubMed:17499941, PubMed:17499941). Involved in immune regulation (PubMed:25477879).|||Expressed mainly in antigen-presenting immune cells, liver, kidney, brain, and placenta (PubMed:25691885, PubMed:17671174). Highly expressed in kidney, followed by epididymis and liver (at protein level) (PubMed:17499941). Detected in the tails of the spermatozoa in the testis and in the kidney tubules (at protein level) (PubMed:17499941). Constitutively expressed in brain.|||Ido1 and Ido2 are 2 distinct enzymes which catalyze the same reaction. Ido2 Km for tryptophan is much higher than that of Ido1. Ido2 may play a role as a negative regulator of Ido1 by competing for heme-binding with Ido1. Low efficiency Ido2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency Ido1 enzymes are dispensable in many lower vertebrate lineages. Ido1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals.|||Knockout mice have no apparent defects in embryonic development or hematopoietic differentiation and have wild-type profiles for kynurenine in blood serum and for immune cells in spleen, lymph nodes, peritoneum, thymus and bone marrow. Knockout mice exhibit defects in IDO-mediated T-cell regulation and inflammatory responses (PubMed:25691885). They exhibit defects in allergic or autoimmune responses (PubMed:24402311). http://togogenome.org/gene/10090:Arhgap19 ^@ http://purl.uniprot.org/uniprot/Q8BRH3 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Ano4 ^@ http://purl.uniprot.org/uniprot/Q8C5H1|||http://purl.uniprot.org/uniprot/S4R1L3 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (PubMed:23532839). Does not exhibit calcium-activated chloride channel (CaCC) activity (PubMed:22075693).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be due to an intron retention.|||Membrane|||Predominantly expressed in neuronal tissues. Expressed at low levels in ovary, uterus, heart and brain.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Clcn3 ^@ http://purl.uniprot.org/uniprot/A0A6Q6Q7B9|||http://purl.uniprot.org/uniprot/P51791|||http://purl.uniprot.org/uniprot/Q790S0|||http://purl.uniprot.org/uniprot/Q8K4W8 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 days of development it is expressed throughout the embryo. Later in development (12.5 to 14.5 days of gestation), expression is progressively up-regulated in neurons of the brain and the spinal cord, in all cranial sensory ganglia and in the sympathetic dorsal root ganglia.|||Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.|||Brain, heart, pancreas, kidney, liver, lung, retina, olfactory bulb, and spinal cord.|||Brain, pancreas, kidney, liver, lung, retina, olfactory bulb, and spinal cord.|||Cell membrane|||Detected in kidney, in the apical part of proximal tubule cells (at protein level). Expressed at high levels in the kidney while a low level expression is seen in the brain. Within the brain, it is prominent in the hippocampus, cerebral cortex and olfactory bulb.|||Early endosome membrane|||Endosome membrane|||Expressed at high levels in the liver and at low levels in the brain.|||Inhibited by Cd(2+).|||Late endosome membrane|||Lysosome membrane|||May influence large dense-core vesicle exocytosis in adrenal chromaffin cells.|||Membrane|||Monomer and homodimer (PubMed:28972156). Forms heterodimers with CLCN4 (PubMed:28972156).|||N-glycosylated.|||Pancreas, kidney, liver, lung and retina.|||Recycling endosome membrane|||Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (PubMed:24603049, PubMed:26342074, PubMed:28972156). Facilitates endosomal acidification and chloride accumulation in hepatocytes (PubMed:15504734).|||Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (PubMed:26342074). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (By similarity). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).|||Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons.|||secretory vesicle membrane http://togogenome.org/gene/10090:Pnp2 ^@ http://purl.uniprot.org/uniprot/Q9D8C9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PNP/MTAP phosphorylase family.|||Homotrimer.|||The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate. http://togogenome.org/gene/10090:Ezh2 ^@ http://purl.uniprot.org/uniprot/Q3TZH6|||http://purl.uniprot.org/uniprot/Q571L5|||http://purl.uniprot.org/uniprot/Q61188|||http://purl.uniprot.org/uniprot/Q6AXH7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. EZ subfamily.|||Chromosome|||Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By similarity). The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By similarity). The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit (By similarity). Interacts with HDAC1 and HDAC2 (By similarity). Binds ATRX via the SET domain (By similarity). Interacts with PRAME (By similarity). Interacts with CDYL (By similarity). Interacts with EED. Interacts with BMAL1. Interacts with CLOCK and CRY1. Interacts with DNMT3L; the interaction is direct (PubMed:24074865). Interacts with EZHIP; the interaction blocks EZH2 methyltransferase activity (PubMed:31451685). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). Interacts with ARMC12 (By similarity). Interacts with ZMYND8; the interaction is dependent on the presence of chromatin (By similarity).|||Death early in development. Embryos cease development following implantation or initiate but fail to complete gastrulation.|||Expressed in both adult and embryo with highest levels in early embryogenesis. Expressed in the fertilized oocyte. Expression decreases during differentiation of ES cells and during senescence of MEFs. Expression increases in prostate during prostate tumor development.|||Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases stability of EZH2 and facilitates the formation of H3K27me3 by the PRC2/EED-EZH2 complex.|||Nucleus|||Phosphorylated by AKT1 (By similarity). Phosphorylation by AKT1 reduces methyltransferase activity. Phosphorylation at Thr-345 by CDK1 and CDK2 promotes maintenance of H3K27me3 levels at EZH2-target loci, thus leading to epigenetic gene silencing (By similarity).|||Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2. Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription.|||Present in actively dividing cells (PubMed:19026781). Widely expressed in early embryos (PubMed:19026781). In later embryogenesis, expression restricted to central and peripheral nervous system, liver and thymus (PubMed:19026781). In adult, highest expression in spleen, testis and placenta (PubMed:19026781, PubMed:31451685). Lower levels in intestine, muscle and ovary and very low levels in brain and liver (PubMed:19026781, PubMed:31451685). No expression in heart, thyroid gland, lung and kidney (PubMed:19026781).|||Repressed by the microRNA (miRNA) miR-26a.|||Sumoylated. http://togogenome.org/gene/10090:Dcp1b ^@ http://purl.uniprot.org/uniprot/B9EIX0 ^@ Similarity ^@ Belongs to the DCP1 family. http://togogenome.org/gene/10090:Abtb2 ^@ http://purl.uniprot.org/uniprot/Q7TQI7 ^@ Function ^@ May be involved in the initiation of hepatocyte growth. http://togogenome.org/gene/10090:Ark2n ^@ http://purl.uniprot.org/uniprot/Q0VAW6|||http://purl.uniprot.org/uniprot/Q8BH50 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AMPK substrate important for exercise capacity and skeletal muscle function. Required for normal contraction-induced signaling.|||Detected in brain, liver, lung, kidney, heart, spleen, skeletal muscle and spinal cord.|||Interacts with CSNK2B (via KSSR). Interacts with JUN; the interaction is mediated by CSNK2B.|||Kockout mice have an increase in white adipose tissue mass in both sexes and a decrease in heart mass only in males but no difference in the mass of other organs (PubMed:35882232). Upon treadmill exercise to exhaustion, mutants fatigue earlier than wild types running 20% less distance (PubMed:35882232).|||Nucleus|||Phosphorylated at Ser-67 by AMPK. In skeletal muscle, phosphorylation is induced by exercise and seems to increase muscle contractile function. http://togogenome.org/gene/10090:Ecsit ^@ http://purl.uniprot.org/uniprot/A0A0R4J174|||http://purl.uniprot.org/uniprot/Q9QZH6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a role in different signaling pathways including TLRs and IL-1 pathways or innate antiviral induction signaling (PubMed:10465784). Plays a role in the activation of NF-kappa-B by forming a signal complex with TRAF6 and TAK1/MAP3K7 to activate TAK1/MAP3K7 leading to activation of IKKs. Once ubiquitinated, interacts with the dissociated RELA and NFKB1 proteins and translocates to the nucleus where it induces NF-kappa-B-dependent gene expression. Plays a role in innate antiviral immune response by bridging the pattern recognition receptors RIGI and MDA5/IFIT1 to the MAVS complex at the mitochondrion (By similarity). Promotes proteolytic activation of MAP3K1. Involved in the BMP signaling pathway (PubMed:14633973). Required for normal embryonic development (By similarity).|||As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.|||Belongs to the ECSIT family.|||Cytoplasm|||Detected in heart, brain, lung, liver, skeletal muscle, kidney and testis. Detected in embryonic mesoderm and epiblast, and in extraembryonic ectoderm.|||Interacts with MAP3K1, SMAD4 and TRAF6. Interacts with SMAD1 only after BMP4-treatment (PubMed:14633973, PubMed:10465784). Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Interacts with NDUFAF1. Interacts with ACAD9. Interacts with TRIM59 (PubMed:22588174). Interacts with TMEM70 and TMEM242 (By similarity). Interacts (when ubiquitinated) with NF-kappa-B subunits RELA and NFKB1 (By similarity). Interacts with RIGI, IFIT1 and MAVS; these interactions promote RLR-mediated type I IFN induction (By similarity). Interacts with SQSTM1; this interaction inhibits TLR4 signaling via functional regulation of the TRAF6-ECSIT complex (By similarity). Interacts with cereblon/CRBN; this interaction inhibits the ubiquitination of ECSIT (By similarity).|||Macrophages lacking ECSIT exhibit profound disruption of mitochondrial complex I/CI. Deletion lead to increased dependence on glycolysis and mitochondrial respiratory chain dysfunction.|||Mitochondrion|||Nucleus|||Ubiquitinated on Lys-372; leading to translocation in the nucleus together with RELA and NFKB1 and expression of NF-kappa-B-dependent genes. http://togogenome.org/gene/10090:Hibadh ^@ http://purl.uniprot.org/uniprot/Q99L13 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HIBADH-related family. 3-hydroxyisobutyrate dehydrogenase subfamily.|||Homodimer.|||Mitochondrion http://togogenome.org/gene/10090:Lim2 ^@ http://purl.uniprot.org/uniprot/P56563 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PMP-22/EMP/MP20 family.|||Defects in Lim2 are the cause of the cataractous mouse mutant with total opacity of lens 3 (To3). Mice heterozygous or homozygous for the To3 mutation have total opacity of the lens with a dense cataract. In addition, the To3/To3 homozygotes exhibit microphthalmia, abnormally small eyes.|||Membrane|||Present in the thicker 16-17 nm junctions of mammalian lens fiber cells, where it may contribute to cell junctional organization. Acts as a receptor for calmodulin. May play an important role in both lens development and cataractogenesis.|||Seems to be associated with itself or another lens membrane component via disulfide bonds. http://togogenome.org/gene/10090:Mtcl1 ^@ http://purl.uniprot.org/uniprot/Q3UHU5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the SOGA family.|||Homodimer. Isoform 1 interacts with MARK2; the interaction increases MARK2 microtubule-binding ability. Associates (via N- and C-terminus domains) with microtubule filaments.|||Lateral cell membrane|||Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation. Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells.|||Midbody|||cytoskeleton|||spindle pole http://togogenome.org/gene/10090:Clec14a ^@ http://purl.uniprot.org/uniprot/Q8VCP9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ntaq1 ^@ http://purl.uniprot.org/uniprot/A0A2I3BQY8|||http://purl.uniprot.org/uniprot/Q80WB5|||http://purl.uniprot.org/uniprot/Q9CWD7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NTAQ1 family.|||Mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, an important step in N-end rule pathway of protein degradation. Conversion of the resulting N-terminal glutamine to glutamate renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. Does not act on substrates with internal or C-terminal glutamine and does not act on non-glutamine residues in any position. Does not deaminate acetylated N-terminal glutamine. With the exception of proline, all tested second-position residues on substrate peptides do not greatly influence the activity. In contrast, a proline at position 2, virtually abolishes deamidation of N-terminal glutamine.|||Monomer.|||Nucleus|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Sec1 ^@ http://purl.uniprot.org/uniprot/Q8CDC9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 11 family.|||Golgi stack membrane|||Membrane http://togogenome.org/gene/10090:Rapgef3 ^@ http://purl.uniprot.org/uniprot/Q8VCC8 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Guanine nucleotide exchange factor (GEF) for RAP1A and RAP2A small GTPases that is activated by binding cAMP. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which it activates the PI3K gamma complex and which is involved in angiogenesis. Plays a role in the modulation of the cAMP-induced dynamic control of endothelial barrier function through a pathway that is independent on Rho-mediated signaling. Required for the actin rearrangement at cell-cell junctions, such as stress fibers and junctional actin (By similarity).|||Interacts with PDE3B and PIK3R6; form a signaling complex that regulates phosphatidylinositol 3-kinase gamma in angiogenesis.|||It is uncertain whether Met-1 or Met-43 is the initiator.|||Membrane|||The DEP domain is involved in membrane localization independent from regulation by cAMP. http://togogenome.org/gene/10090:Vmn2r58 ^@ http://purl.uniprot.org/uniprot/K7N6V2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cc2d1a ^@ http://purl.uniprot.org/uniprot/Q8K1A6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CC2D1 family.|||Cytoplasm|||Expressed at 12 dpc throughout the ventricular zone and developing cortical plate and ganglionic eminences. At 16 dpc detected throughout the brain but most strongly in the cortical plate. At postnatal day 3 expressed widely with strong expression in cerebral cortex and hippocampus.|||Highly expressed in brain, expression is enriched in the gray matter and strongest in the olfactory bulb.|||Knockout mice die soon after birth, apparently because of their inability to breathe.|||Nucleus|||The C2 domain is required for the repression.|||Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. The combination of calcium and ATP specifically inactivates the binding with FRE. May play a role in the altered regulation of HTR1A associated with anxiety and major depression. Mediates HDAC-independent repression of HTR1A promoter in neuronal cell. Performs essential function in controlling functional maturation of synapses.|||centrosome http://togogenome.org/gene/10090:Vcp ^@ http://purl.uniprot.org/uniprot/Q01853 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Endoplasmic reticulum|||Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Binds to a heterodimer of NPLOC4 and UFD1, binding to this heterodimer inhibits Golgi-membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Part of a ternary complex containing NPLOC4, UFD1 and VCP. Interacts with NSFL1C-like protein p37; the complex has membrane fusion activity and is required for Golgi and endoplasmic reticulum biogenesis. Interacts with RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of the endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts directly with AMFR/gp78 (via its VIM). Interacts with RHBDD1 (via C-terminal domain). Interacts with SPRTN; leading to recruitment to stalled replication forks. Interacts with SELENOS and SYVN1, as well as with DERL1 (via SHP-box motif), DERL2 and DERL3; which probably transfer misfolded proteins from the ER to VCP. Interacts with SVIP. Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Directly interacts with UBXN4 and RNF19A. Interacts with CASR. Interacts with UBE4B and YOD1. Interacts with clathrin. Interacts with RNF103. Interacts with TRIM13 and TRIM21. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of the endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Interacts directly with AMFR/gp78 (via its VIM). Interacts with WASHC5. Interacts with UBOX5. Interacts (via N- terminus) with UBXN7, UBXN8, and probably several other UBX domain-containing proteins (via UBX domains); the interactions are mutually exclusive with VIM-dependent interactions such as those with AMFR and SELENOS. Forms a complex with UBQLN1 and UBXN4 (By similarity). Interacts (via the PIM motif) with RNF31 (via the PUB domain) (By similarity). Interacts with RIGI and RNF125; interaction takes place when RIGI is ubiquitinated via'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI (By similarity). Interacts with BAG6 (By similarity). Interacts with UBXN10 (By similarity). Interacts with UBXN6; the interaction with UBXN6 is direct and competitive with UFD1 (By similarity). Forms a ternary complex with CAV1 and UBXN6. Interacts with PLAA, UBXN6 and YOD1; may form a complex involved in macroautophagy (By similarity). Interacts with ANKZF1 (By similarity). Interacts with ubiquitin-binding protein FAF1 (By similarity). Interacts with ZFAND2B (via VIM motif); the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with ZFAND1 (via its ubiquitin-like region); this interaction occurs in an arsenite-dependent manner (By similarity). Interacts with CCDC47 (PubMed:25009997). Interacts with LMBR1L and UBAC2 (PubMed:31073040). Interacts with ATXN3 (By similarity). Interacts with TEX264; bridging VCP to covalent DNA-protein cross-links (DPCs) (By similarity).|||ISGylated.|||Methylation at Lys-315 catalyzed by VCPKMT is increased in the presence of ASPSCR1. Lys-315 methylation may decrease ATPase activity (By similarity).|||Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A. Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. Involved in clearance process by mediating G3BP1 extraction from stress granules (By similarity). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168-dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage. Together with SPRTN metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (By similarity). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (PubMed:33590678). Mediates extraction of PARP1 trapped to chromatin: recognizes and binds ubiquitinated PARP1 and promotes its removal (By similarity). Required for cytoplasmic retrotranslocation of stressed/damaged mitochondrial outer-membrane proteins and their subsequent proteasomal degradation. Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy. Acts as a negative regulator of type I interferon production by interacting with RIGI: interaction takes place when RIGI is ubiquitinated via 'Lys-63'-linked ubiquitin on its CARD domains, leading to recruit RNF125 and promote ubiquitination and degradation of RIGI. May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation. May more particularly play a role in caveolins sorting in cells. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway.|||Nucleus|||Phosphorylated by tyrosine kinases in response to T-cell antigen receptor activation. Phosphorylated in mitotic cells.|||Stress granule|||The N-terminal domain shows evolutionary conservation with that of PEX1, and is able to bind phospholipids with a preference for phosphatidylinositol mono- and bisphosphates.|||The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31.|||cytosol http://togogenome.org/gene/10090:Matr3 ^@ http://purl.uniprot.org/uniprot/Q8K310 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs. May bind to specific miRNA hairpins.|||Nucleus matrix|||Part of a complex consisting of SFPQ, NONO and MATR3. Interacts with AGO1 and AGO2 (By similarity). Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity. Interacts with TARDBP. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA. Interacts with FUS. Interacts with IGF2BP1. Interacts with IGF2BP2 and IGF2BP3. http://togogenome.org/gene/10090:Coro7 ^@ http://purl.uniprot.org/uniprot/Q9D2V7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat coronin family.|||Cytoplasmic vesicle|||F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via 'Lys-33'-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network, where it promotes actin polymerization, thereby facilitating post-Golgi trafficking. May play a role in the maintenance of the Golgi apparatus morphology (By similarity).|||Golgi apparatus membrane|||In the adult, widely expressed with highest levels in brain, thymus and kidney and low levels in skeletal and heart muscle. Not expressed in lung. In the eye, strongly expressed in the outer plexiform layer of the retina. In the intestine, expressed both in terminally differentiated epithelial cells and in crypt epithelium. In the embryo, strongest expression is seen in brain, thymus, intestine, apical epidermal layers of the skin and developing lens fibers of the eye.|||In the embryo, expressed from 5 dpc and levels increase strongly until 15 dpc.|||Interacts with clathrin adapter AP1 complex. This interaction takes place at Golgi membranes and not AP1-positive endosomal membranes. Interacts (when ubiquitinated at Lys-469) with EPS15 (By similarity).|||The membrane-associated form is phosphorylated on tyrosine residues.|||Ubiquitinated via 'Lys-33'-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex: 'Lys-33'-linked ubiquitination promotes interaction with EPS15 and facilitates actin polymerization at the trans-Golgi network, thereby facilitating post-Golgi trafficking. Deubiquitinated by ZRANB1/TRABID (By similarity).|||cytosol|||trans-Golgi network http://togogenome.org/gene/10090:Gpr31b ^@ http://purl.uniprot.org/uniprot/F8VQN3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice exhibit a reduced response to enteric bacteria, showing defective dendrite protrusions of CX3CR1(+) cells in the small intestine (PubMed:30675063). Under ischemia/reperfusion injury, liver dysfunction, cell death and inflammatory induction are consistently and significantly inhibited at 6 hours after reperfusion in GPR31-deficient mice (PubMed:29227475).|||High-affinity receptor for 12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-S-HETE), with much lower affinities for other HETE isomers (By similarity) (PubMed:29227475). 12-S-HETE is a eicosanoid, a 12-lipoxygenase (ALOX12) metabolite of arachidonic acid, involved in many physiologic and pathologic processes, such as cell growth, adhesion, inflammation and cancer promotion. 12-S-HETE-binding leads to activation of ERK1/2 (MAPK3/MAPK1), MEK, and NF-kappa-B pathways and leads to cell growth. Plays a crucial role for proliferation, survival and macropinocytosis of KRAS-dependent cancer cells by mediating the translocation of KRAS from the endoplasmic reticulum to the plasma membrane (PM) and its association with the PM (By similarity). Contributes to enhanced immune responses by inducing dendrite protrusion of small intestinal CX3CR1(+) phagocytes for the uptake of luminal antigens (PubMed:30675063). Acts also as a key receptor for 12-(S)-HETE-mediated liver ischemia reperfusion injury (PubMed:29227475).|||Interacts with KRAS; in a farnesylation-dependent manner.|||Proton-sensing G protein-coupled receptor. http://togogenome.org/gene/10090:Lonp2 ^@ http://purl.uniprot.org/uniprot/Q8BK80|||http://purl.uniprot.org/uniprot/Q9DBN5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import. May indirectly regulate peroxisomal fatty acid beta-oxidation through degradation of the self-processed forms of TYSND1.|||Belongs to the peptidase S16 family.|||Interacts with PEX5. Interacts with TYSND1 (By similarity). May interact with enzymes involved in beta-oxidation of fatty acids, including ACOX1/AOX (By similarity).|||Peroxisome matrix http://togogenome.org/gene/10090:B3gnt8 ^@ http://purl.uniprot.org/uniprot/Q8R3I9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylglucosaminyltransferase that plays a role in the elongation of specific branch structures of multiantennary N-glycans. Has strong activity towards tetraantennary N-glycans and 2,6 triantennary glycans (By similarity).|||Golgi apparatus membrane|||Interacts with B3GNT2; this interaction greatly increases B3GNT2 catalytic activity, independently of B3GNT8 enzymatic activity. http://togogenome.org/gene/10090:Or2bd2 ^@ http://purl.uniprot.org/uniprot/Q7TQV3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aadat ^@ http://purl.uniprot.org/uniprot/Q9WVM8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Expressed mainly in kidney and to a lesser amount in liver and brain.|||Homodimer.|||Mitochondrion|||Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro) (By similarity). http://togogenome.org/gene/10090:Vsir ^@ http://purl.uniprot.org/uniprot/Q9D659 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ At the cell surface, may be cleaved by MMP14.|||Cell membrane|||Detected in 7-day and 17-day embryos.|||Expressed in spleen, thymus, bone marrow, lymph node, and in T-cells within the lamina propria of the small intestine (PubMed:21768399). Detected on CD4+ and CD8+ T-cells, bone marrow-derived dendritic cells (BMDCs), peritoneal macrophages, neutrophils, and natural killer (NK) cells (PubMed:21768399). In spleen and lymph nodes, highly expressed on CD4+ T-cell populations, and at lower levels on CD8+ T-cells (PubMed:21383057). In thymus, has low expression on CD4+ cells and CD8+ cells, and not detected on CD4+CD8+ cells (PubMed:21383057). Expressed in splenic and peritoneal CD11b cells (PubMed:21383057). Not detected in most B cells and NK cells (at protein level) (PubMed:21383057). Also detected at lower levels in non-hematopoeitic tissues such as heart, brain, lung, kidney, muscle, ovary, and testis (PubMed:21768399, PubMed:21383057).|||Immunoregulatory receptor which inhibits the T-cell response (PubMed:21383057, PubMed:24743150, PubMed:25267631). May promote differentiation of embryonic stem cells, by inhibiting BMP4 signaling (PubMed:20042595). May stimulate MMP14-mediated MMP2 activation (By similarity).|||N-glycosylated.|||Up-regulated by phorbol 12-myristate 13-acetate (PMA) and the cytokine IFNG.|||Viable and fertile (PubMed:24743150, PubMed:25267631). At birth, lymphocyte populations in bone marrow, spleen and lymph nodes appear to be normal (PubMed:24743150, PubMed:25267631). Frequencies of activated peripheral T-cells are increased in older animals (PubMed:24743150, PubMed:25267631). Levels of the inflammatory cytokines CCL11, CXCL10, CCL2 and CXCL9 are significantly increased (PubMed:25267631). Tissues show signs of chronic inflammation, however this does not progress to overt autoimmune disease (PubMed:25267631). http://togogenome.org/gene/10090:Abcb7 ^@ http://purl.uniprot.org/uniprot/Q61102 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.|||Exports glutathione-coordinated iron-sulfur clusters such as [2Fe-2S]-(GS)4 cluster from the mitochondria to the cytosol in an ATP-dependent manner allowing the assembly of the cytosolic iron-sulfur (Fe/S) cluster-containing proteins and participates in iron homeostasis (PubMed:16424901, PubMed:16467350). Moreover, through a functional complex formed of ABCB7, FECH and ABCB10, also plays a role in the cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). In cardiomyocytes, regulates cellular iron homeostasis and cellular reactive oxygen species (ROS) levels through its interaction with COX4I1 (By similarity). May also play a role in hematopoiesis (PubMed:17192398).|||Heterozygous females for Abcb7 with a maternally inherited mutant allele die embryonically, due to a defect in the extra-embryonic visceral endoderm, while heterozygous females with a paternally inherited mutant allele are viable (PubMed:16467350). The systemic and tissue-specific deletion of ABCB7 in most organs, including CNS and bone marrow, is lethal (PubMed:16467350). Conditionnal knockout in hepatocyte causes periportal hepatocellular iron deposition with characteristic round structures and leads to iron-dependent regulation of IRP1 protein (PubMed:16467350, PubMed:16424901).|||Homodimer or heterodimer. Interacts with C10orf88/PAAT (By similarity). Forms a complex with ABCB10 and FECH, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). Interacts with FECH (PubMed:30765471). Interacts with ATP5F1A. Interacts with COX4I1; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ccnj ^@ http://purl.uniprot.org/uniprot/Q3TZI6 ^@ Similarity ^@ Belongs to the cyclin family. Cyclin J subfamily. http://togogenome.org/gene/10090:S1pr1 ^@ http://purl.uniprot.org/uniprot/O08530 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Embryonic lethality, due to impaired vascular maturation and defects in heart development. Embryos appear normal up to 11.5 dpc, but after that they display massive hemorrhage. They have a normally arborized vascular network, but present excessive sprouting angiogenesis and severe aberrations in vessel size. Their aorta and other arteries are not properly enveloped by vascular smooth muscle cells, causing hemorrhage. Likewise, small blood vessels show a marked reduction in the number of vascular pericytes. In addition, mutants display defects in heart morphogenesis, with reduced myocardial tissue and altered morphology of the heart wall and the trabeculae (PubMed:11032855, PubMed:14732704, PubMed:21668976, PubMed:22951644). At 12.5 dpc, mutant embryos also show a massive cell loss in the forebrain (PubMed:16314531). Conditional knockout in endothelial cells leads to the same vascular maturation defect as that seen in homozygous knockout mice (PubMed:12869509). Conditional knockout in fibroblasts leads to defects in chemotaxis, probably due to defects in the activation of SRC and PTK2/FAK1, resulting in defects in the reorganization of the actin cytoskeleton and lamellipodia formation (PubMed:11726541). A T-cell-specific knockout leads to a defect in the egress of mature T-cells from the thymus into the periphery (PubMed:14737169). Conditional knockout in osteoclast precursors leads to osteoporosis, due to impaired migration of osteoclast precursors and increased osteoclast attachment to the bone (PubMed:19204730).|||Endosome|||Expressed in a wide variety of tissues with highest levels in brain, heart and spleen. Lower levels found in kidney, liver, lung, muscle, placenta, thymus, and uterus. Very low levels in intestine, stomach and testis. According to PubMed:9931453, expressed modestly in apparent endothelial cells surrounding some blood vessels (e.g. aortic trunk).|||G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis. Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.|||Interacts with GNAI1 and GNAI3.|||Palmitoylated by ZDHHC5. Palmitoylation is required for targeting to plasma membrane, enabling G(i) coupling.|||caveola http://togogenome.org/gene/10090:Arpc1a ^@ http://purl.uniprot.org/uniprot/Q9R0Q6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat ARPC1 family.|||Nucleus|||Probable component of the Arp2/3 complex in which it may replace ARPC1B.|||Probably functions as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks (By similarity). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Tat ^@ http://purl.uniprot.org/uniprot/Q8QZR1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Homodimer.|||Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity for phenylalanine. http://togogenome.org/gene/10090:Alg8 ^@ http://purl.uniprot.org/uniprot/Q6P8H8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Adds the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc(1)Man(9)GlcNAc(2)-PP-Dol before it is transferred to the nascent peptide (By similarity). Required for PKD1/Polycystin-1 maturation and localization to the plasma membrane of the primary cilia (PubMed:28375157).|||Belongs to the ALG6/ALG8 glucosyltransferase family.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Vps25 ^@ http://purl.uniprot.org/uniprot/A2A4J8|||http://purl.uniprot.org/uniprot/A2A4K0|||http://purl.uniprot.org/uniprot/Q9CQ80 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS25 family.|||Component of a complex at least composed of ELL, SNF8/EAP30, VPS25/EAP20 and VPS36/EAP45 (By similarity). Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS36 and 2 copies of VPS25. Interacts with CFTR; the interaction requires misfolded CFTR. Interacts (via C-terminal half) with the ESCRT-III subunit CHMP6 (via N-terminal half) (By similarity).|||Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL (By similarity).|||Cytoplasm|||Endosome membrane|||Nucleus http://togogenome.org/gene/10090:Hnrnpm ^@ http://purl.uniprot.org/uniprot/Q9D0E1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Identified in the spliceosome C complex (By similarity). Interacts with PPIA/CYPA (By similarity).|||Nucleus|||Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines (By similarity).|||Sumoylated. http://togogenome.org/gene/10090:B3gnt6 ^@ http://purl.uniprot.org/uniprot/Q3USF0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylglucosaminyltransferase that synthesizes the core 3 structure of the O-glycan, an important precursor in the biosynthesis of mucin-type glycoproteins. Plays an important role in the synthesis of mucin-type O-glycans in digestive organs.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Kera ^@ http://purl.uniprot.org/uniprot/O35367 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.|||Binds keratan sulfate chains.|||May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix.|||Selectively expressed in cornea of adult where it is detected in keratocytes but not in scleral cells. In embryo, first detected in periocular mesenchymal cells migrating toward developing cornea on 13.5 dpc; expression gradually restricted to corneal stromal cells on 14.5 to 18.5 dpc. Detected in scleral cells of 15.5 dpc but not in 18.5 dpc embryos.|||extracellular matrix http://togogenome.org/gene/10090:Ugt2b36 ^@ http://purl.uniprot.org/uniprot/Q3UEP4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Cst12 ^@ http://purl.uniprot.org/uniprot/Q9DAN8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Located at the very proximal caput epididymis (at protein level). Expressed in epididymis, Sertoli cells and testis. Also found to be weakly expressed in ovary and prostate.|||May play a specialized role in spermatogenesis.|||Secreted http://togogenome.org/gene/10090:Cyp3a41a ^@ http://purl.uniprot.org/uniprot/Q9JMA7 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Detected immediately after birth in the livers of animals of both sexes, but increases with age in females, whereas it is gradually reduced in males, resulting in predominantly female-specific expression in livers.|||Endoplasmic reticulum membrane|||Expressed in liver. Also expressed in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice.|||Microsome membrane http://togogenome.org/gene/10090:Npr3 ^@ http://purl.uniprot.org/uniprot/P70180 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ANF receptor family.|||Cell membrane|||Defects in Npr3 are the cause of a number of skeletal-overgrowth phenotypes, Longjohn (Lgj), Longjohn-2J (Lgj-2J) and Strigosus (Stri). These are all recessive conditions characterized by an elongated body, thoracic kyphosis, arachnodactyly, and sacral and/or tail kinks, but no significant changes in craniofacial structures (PubMed:10468599).|||Half of the mice dies before weaning. They display reduced ability to concentrate urine, a lower blood pressure, and skeletal abnormalities. Despite a reduced half-life of NPPA in the circulation, the plasma levels of NPPA and NPPB are not affected.|||Has low affinity for peptide hormones in the absence of bound chloride.|||Homodimer; disulfide-linked (By similarity). Interacts with OSTN (PubMed:17951249).|||Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP (PubMed:10377427, PubMed:17951249). May function as a clearance receptor for NPPA, NPPB and NPPC, regulating their local concentrations and effects (PubMed:10377427, PubMed:17951249). May regulate diuresis, blood pressure and skeletal development (PubMed:10377427). Does not have guanylate cyclase activity (PubMed:10377427). http://togogenome.org/gene/10090:Dhrs7c ^@ http://purl.uniprot.org/uniprot/Q8CHS7 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Expressed in skeletal muscle and cardiac muscle (PubMed:21995425, PubMed:22143674, PubMed:27806939). Also expressed in liver, kidney, adipocytes and skin (PubMed:21995425, PubMed:22143674).|||In skeletal muscle, expressed in differentiated myotubes but not in undifferentiated myoblasts.|||Induced by all-trans-retinoic acid (at transcriptional level).|||NADH-dependent oxidoreductase which catalyzes the oxidation of all-trans-retinol to all-trans-retinal (PubMed:21995425). Plays a role in the regulation of cardiac and skeletal muscle metabolic functions (PubMed:21995425, PubMed:27806939, PubMed:29330505) (Probable). Maintains Ca(2+) intracellular homeostasis by repressing Ca(2+) release from the sarcoplasmic reticulum (SR) in myotubes, possibly through local alternations in NAD/NADH or retinol/retinal (PubMed:21995425). Also plays a role in Ca(2+) homeostasis by controlling Ca(2+) overload in the cytosol and the SR in myotubes (PubMed:27806939). Involved in glucose uptake into skeletal muscles and muscle performance by activating PI3K and mTORC2-mediated AKT1 phosphorylation signaling pathways, possibly through the action of its downstream catalytic product all-trans-retinoic acid (PubMed:29330505).|||Sarcoplasmic reticulum membrane|||The N-terminus region encompasses a short hydrophobic sequence bound to the sarcoplasmic reticulum membrane, whereas the C-terminus catalytic domain faces the myoplasm. http://togogenome.org/gene/10090:Klk7 ^@ http://purl.uniprot.org/uniprot/Q91VE3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Expressed in skin and, at lower levels, in lung, kidney, brain, heart and spleen. In skin, expressed in high suprabasal keratinocytes and in the luminal parts of hair follicles. Not detected in liver and skeletal muscle.|||Inhibited by Zn2+ and Cu2+ at low micromolar concentrations. Inhibited by SERPINA12 (By similarity).|||May catalyze the degradation of intercellular cohesive structures in the cornified layer of the skin in the continuous shedding of cells from the skin surface. Specific for amino acid residues with aromatic side chains in the P1 position. Cleaves insulin A chain at '14-Tyr-|-Gln-15' and insulin B chain at '6-Leu-|-Cys-7', '16-Tyr-|-Leu-17', '25-Phe-|-Tyr-26' and '26-Tyr-|-Thr-27'. Could play a role in the activation of precursors to inflammatory cytokines.|||Secreted http://togogenome.org/gene/10090:Stk17b ^@ http://purl.uniprot.org/uniprot/Q8BG48 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a positive regulator of apoptosis. Phosphorylates myosin light chains (By similarity).|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.|||Cell membrane|||Endoplasmic reticulum-Golgi intermediate compartment|||Interacts with CHP1; the interaction induces CHP1 to translocate from the Golgi to the nucleus.|||Nucleus http://togogenome.org/gene/10090:Ubxn10 ^@ http://purl.uniprot.org/uniprot/Q8BG34 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UBXN10 family.|||Interacts with CLUAP1; the interaction is direct and mediates interaction with the intraflagellar transport complex B (IFT-B). Interacts with VCP; the interaction is direct.|||VCP/p97-binding protein required for ciliogenesis. Acts as a tethering factor that facilitates recruitment of VCP/p97 to the intraflagellar transport complex B (IFT-B) in cilia. UBX domain-containing proteins act as tethering factors for VCP/p97 and may specify substrate specificity of VCP/p97.|||cilium http://togogenome.org/gene/10090:Gpr18 ^@ http://purl.uniprot.org/uniprot/Q8K1Z6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Expressed in the eye including cornea, retina, iris and ciliary epithelium (at protein level) (PubMed:23461720). Expressed in spleen, liver and lymphocytes with highest expression levels in intestinal intraepithelial lymphocytes (PubMed:25348153, PubMed:26197390).|||No visible phenotype (PubMed:26197390). However, reduced number of CD8alphaalpha gammadeltaT IELs has been reported (PubMed:25348153).|||Receptor for endocannabinoid N-arachidonyl glycine (NAGly) (By similarity). However, conflicting results about the role of NAGly as an agonist are reported (PubMed:23104136). Can also be activated by plant-derived and synthetic cannabinoid agonists (By similarity). The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase (By similarity). May contribute to regulation of the immune system (By similarity). Is required for normal homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs) in small intstine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant (PubMed:25348153, PubMed:26197390). Plays a role in hypotensive responses, mediating reduction in intraocular and blood pressure (PubMed:23461720, PubMed:27893106). Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis (By similarity). http://togogenome.org/gene/10090:Tas2r108 ^@ http://purl.uniprot.org/uniprot/Q9JKT3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in 15% taste bud cells in circumvallate and foliate papillae but only in 2% in fungiform papillae.|||Gustducin-coupled receptor for denatonium and N(6)-propyl-2-thiouracil implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5. In airway epithelial cells, binding of denatonium increases the intracellular calcium ion concentration and stimulates ciliary beat frequency (By similarity).|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell.|||cilium membrane http://togogenome.org/gene/10090:Cep104 ^@ http://purl.uniprot.org/uniprot/Q80V31 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CCP110 and CEP97. Interacts with ARMC9, TOGARAM1, CCDC66 and CSPP1.|||Required for ciliogenesis and for structural integrity at the ciliary tip.|||centriole|||centrosome|||cilium|||spindle pole http://togogenome.org/gene/10090:Pla2g4b ^@ http://purl.uniprot.org/uniprot/B7ZCM8|||http://purl.uniprot.org/uniprot/P0C871|||http://purl.uniprot.org/uniprot/Q06G06 ^@ Activity Regulation|||Caution|||Domain|||Function|||Subcellular Location Annotation ^@ Activated by cytosolic Ca(2+) in the presence of cardiolipin. Activated by phosphoinositides. Inhibited by electrophilic ketone inhibitors.|||Calcium-dependent phospholipase A1 and A2 and lysophospholipase that may play a role in membrane phospholipid remodeling. Cleaves the ester bond of the fatty acyl group attached to the sn-1 or sn-2 position of phospholipids (phospholipase A1 and A2 activity, respectively), producing lysophospholipids that may be used in deacylation-reacylation cycles. The PLA1 versus PLA2 activity ratio appears to depend on the phospholipid headgroup, with mainly PLA2 activity toward anionic phospholipids such as phosphatidylglycerols. Hydrolyzes with high efficiency lysophospholipids enabling complete deacylation.|||Early endosome membrane|||Mitochondrion membrane|||Most tissues also express read-through transcripts from this gene into the upstream gene (Jmjd7), some of which may encode fusion proteins.|||The N-terminal C2 domain associates with lipid membranes upon calcium binding.|||The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity).|||cytosol http://togogenome.org/gene/10090:Stat5a ^@ http://purl.uniprot.org/uniprot/B2C3G8|||http://purl.uniprot.org/uniprot/P42230|||http://purl.uniprot.org/uniprot/Q3UZ79|||http://purl.uniprot.org/uniprot/Q9JIA0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transcription factor STAT family.|||Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation.|||Cytoplasm|||Forms a homodimer or a heterodimer with a related family member. Interacts with NCOA1 and SOCS7 (By similarity). Binds NR3C1 (PubMed:9528750). Interacts with ERBB4 (PubMed:10508857, PubMed:16837552). Interacts with EBF4 (By similarity).|||ISGylated.|||In the virgin, found in most tissues except brain and muscle. During lactation, abundantly found in mammary tissue, as well as in other secretory organs such as salivary gland and seminal vesicle.|||Nucleus|||Tyrosine phosphorylated in response to KITLG/SCF, IL2, IL3, IL7, IL15, CSF2/GMCSF, GH1, PRL, EPO and THPO (PubMed:16837552). Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus (PubMed:21135090). Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Tyrosine phosphorylation is required for DNA-binding activity and dimerization (PubMed:7720707). Serine phosphorylation is also required for maximal transcriptional activity (By similarity). Tyrosine phosphorylated in response to signaling via activated FLT3; wild-type FLT3 results in much weaker phosphorylation than constitutively activated mutant FLT3 (PubMed:11090077, PubMed:21262971). Alternatively, can be phosphorylated by JAK2 at Tyr-694 (By similarity). http://togogenome.org/gene/10090:Zfp781 ^@ http://purl.uniprot.org/uniprot/Q0P5U5 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Utp3 ^@ http://purl.uniprot.org/uniprot/Q9JI13 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAS10 family.|||Citrullinated by PADI4.|||Detected mainly in subsets of neuronal cells of the brain. In the 17.5 dpc embryo, mainly expressed in the olfactory bulb and cerebral cortex. Postnatally, additionally expressed in the cerebellar cortex, most strongly in the hippocampus.|||Essential for gene silencing: has a role in the structure of silenced chromatin. Plays a role in the developing brain. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Expressed throughout development.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||nucleolus http://togogenome.org/gene/10090:Or5ak4 ^@ http://purl.uniprot.org/uniprot/Q7TRA2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wrnip1 ^@ http://purl.uniprot.org/uniprot/Q91XU0 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1 subfamily.|||Cytoplasm|||Due to intron retention.|||Forms homooligomers, possibly octamers. Directly interacts with POLD1, POLD2 and POLD4 (By similarity). Interacts with the N-terminal domain of WRN (By similarity). Interacts (via UBZ4-type zinc finger) with monoubiquitin and polyubiquitin. Interacts with TRIM14 and PPP6C; these interactions positively regulate the RIGI signaling pathway (By similarity).|||Functions as a modulator of initiation or reinitiation events during DNA polymerase delta-mediated DNA synthesis. In the presence of ATP, stimulation of DNA polymerase delta-mediated DNA synthesis is decreased. Also plays a role in the innate immune defense against viruses. Stabilizes the RIGI dsRNA interaction and promotes RIGI 'Lys-63'-linked polyubiquitination. In turn, RIGI transmits the signal through mitochondrial MAVS.|||Nucleus|||Sumoylated with SUMO1 and SUMO2/3.|||The UBZ4-type zinc finger binds ubiquitin.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Scaf8 ^@ http://purl.uniprot.org/uniprot/Q6DID3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Anti-terminator protein required to prevent early mRNA termination during transcription. Together with SCAF4, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins. Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation. Independently of SCAF4, also acts as a positive regulator of transcript elongation.|||Interacts with POLR2A; via C-terminal heptapeptide repeat domain (CTD) phosphorylated at 'Ser-2' and 'Ser-5' (PubMed:9528809). Identified in a complex with CDC5L and other spliceosomal proteins (By similarity).|||Nucleus|||Nucleus matrix http://togogenome.org/gene/10090:Col25a1 ^@ http://purl.uniprot.org/uniprot/Q99MQ5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed predominantly in neurons with low levels also detected in heart, testis and eye.|||Forms homodimers and homotrimers. Binds to the fibrillized forms of amyloid-beta protein 40 (beta-APP40) and amyloid-betad protein 42 (beta-APP42). Found associated with beta-APP42 more frequently than with beta-APP40 (By similarity).|||Glycosylated.|||Hydroxylated on proline and lysine residues.|||Inhibits fibrillization of amyloid-beta peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin (By similarity).|||Membrane|||Undergoes proteolytic cleavage by furin protease to yield the soluble collagen-like Alzheimer amyloid plaque component. http://togogenome.org/gene/10090:Edn1 ^@ http://purl.uniprot.org/uniprot/P22387|||http://purl.uniprot.org/uniprot/Q544E0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the endothelin/sarafotoxin family.|||Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells (By similarity). Also binds the DEAR/FBXW7-AS1 receptor (PubMed:16293765).|||Expression in lung is low at 17.5 dpc fetal mice and increases progressively into adulthood.|||Highest expression in the adult is in lung. Lower levels found in heart, kidney, brain and intestine. In the embryo, expressed in outer and inner pharyngeal arch surfaces. Also expressed in endothelium of dorsal aorta and arch arteries, and in epithelium of pharyngeal pouches.|||Secreted http://togogenome.org/gene/10090:Myoz3 ^@ http://purl.uniprot.org/uniprot/E9QJU4|||http://purl.uniprot.org/uniprot/Q8R4E4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the myozenin family.|||Expressed specifically in skeletal muscle and is enriched in fast-twitch muscle fibers. Not detected in heart.|||Interacts with ACTN2, LDB3, FLNC, PPP3CA and TCAP.|||Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.|||Z line http://togogenome.org/gene/10090:Tssk1 ^@ http://purl.uniprot.org/uniprot/Q61241 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-174, potentially by autophosphorylation.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Interacts with TSSK2 (PubMed:10781952). Interacts with HSP90; this interaction stabilizes TSSK1 (PubMed:23599433).|||Male mice lacking Tssk1b and Tssk2 are sterile due to haploinsufficiency. chimeras show failure to form elongated spermatids, apoptosis of spermatocytes and spermatids, and the appearance of numerous round cells in the epididymal lumen. Elongating spermatids possess a collapsed mitochondrial sheath.|||Mg(2+) and Mn(2+) were both present in the kinase buffer but Mg(2+) is likely to be the in vivo cofactor.|||Testis-specific serine/threonine-protein kinase required during spermatid development (PubMed:20053632, PubMed:23599433). Phosphorylates 'Ser-281' of TSKS (PubMed:20053632). Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm (PubMed:20053632). During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body (PubMed:20053632).|||Testis-specific. Expressed only in postmeiotic spermatids at the final stages of cytodifferentiation in the seminiferous tubules (at protein level). Not detected in released sperms in the lumen of the seminiferous tubules and the epididymis.|||Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation.|||acrosome|||flagellum http://togogenome.org/gene/10090:Scg2 ^@ http://purl.uniprot.org/uniprot/Q03517|||http://purl.uniprot.org/uniprot/Q4W8U9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chromogranin/secretogranin protein family.|||Binds calcium with a low-affinity.|||Interacts with Secretogranin III/SCG3.|||Neuroendocrine protein of the granin family that regulates the biogenesis of secretory granules.|||Secreted http://togogenome.org/gene/10090:Nup210l ^@ http://purl.uniprot.org/uniprot/Q9D2F7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NUP210 family.|||Membrane http://togogenome.org/gene/10090:Tll1 ^@ http://purl.uniprot.org/uniprot/G3X9F5 ^@ Caution|||Cofactor ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Foxn4 ^@ http://purl.uniprot.org/uniprot/Q8K3Q3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Animals display early postnatal lethality, while survivors exhibit noticeable body size reduction starting at P8. At P8 and P20, retinas are reduced in thickness with the inner nuclear layer, inner plexiform layer and ganglion cell layer much thinner than in wild type and lack horizontal cells as well as amacrine cells. In lungs, mutants show dilated alveoli with thin walls.|||Expressed in both neural and non-neural tissues of the embryo. In the nervous system, its expression is detected only in a few selected central nervous system tissues including the midbrain, hindbrain, spinal cord and retina while absent from the peripheral nervous system. At about 9.5 dpc-10.5 dpc, commences its expression in the dorsal mesenphalon, ventral rhombencephalon and ventral spinal cord. In the spinal cord, is found in p2 progenitor cells but not in mature V2a and V2b cells, in other interneuron subtypes or in motoneurons. The expression in the brain and spinal cord becomes weak at 12.5 dpc and disappears by 13.5 dpc. In the central eye, expression starts in the central retina at 11.5 dpc, then gradually becomes abundant in the entire retinal outer neuroblastic layer by 13.5 dpc, but is absent from the inner neuroblastic layer. Starting from P1 and by P7, the expression in the retina gradually disappears from the center to the periphery. In airway system, expression turns on at 14.5 dpc in a small set of cells in the epithelia of the trachea and esophagus, then spreads to the epithelia of bronchi and bronchioles by 15.5 dpc, the expression persists until at least P8 (at protein level).|||Mainly expressed in proliferator progenitor cells in brain and retina rather than differentiated cells. In contrast, is expressed only in postmitotic epithelial cells rather than in proliferative progenitors in the proximal airway.|||Nucleus|||Transcription factor essential for neural and some non-neural tissues development, such as retina and lung respectively. Binds to an 11-bp consensus sequence containing the invariant tetranucleotide 5'-ACGC-3'. During development of the central nervous system, is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating DLL4-NOTCH signaling. Also acts synergistically with ASCL1/MASH1 to activate DLL4-NOTCH signaling and drive commitment of p2 progenitors to the V2b interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development. http://togogenome.org/gene/10090:Clec2d ^@ http://purl.uniprot.org/uniprot/Q91V08 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Constitutively expressed in bone marrow cells. Down-regulated by treatment with 1,25-dihydroxyvitamin D3. Up-regulated in calvarial osteoblast cells by IL-1alpha, IL11, and 1,25-dihydroxyvitamin D3.|||Detected in fetal heart, brain, lung, chondrocytes, perichondrium and osteoblasts, and in adult splenocytes, thymocytes, lymph-node cells, osteoblasts, growth plate chondrocytes and skeletal muscle overlying the bone (at protein level). Ubiquitous. Detected in thymus, bone marrow, lung, gut, heart, skeletal muscle, ovary, spleen, ileum, liver and kidney.|||Homodimer; disulfide-linked.|||N-glycosylated.|||Receptor for KLRB1B that protects target cells against natural killer cell-mediated lysis (PubMed:14990792, PubMed:16751398). Inhibits osteoclast formation (PubMed:11278931, PubMed:12374791). Binds high molecular weight sulfated glycosaminoglycans (PubMed:15123656). http://togogenome.org/gene/10090:Usp44 ^@ http://purl.uniprot.org/uniprot/Q8C2S0 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family. USP44 subfamily.|||Cytoplasm|||Dephosphorylated by CTDP1.|||Deubiquitinase that plays a key regulatory role in the spindle assembly checkpoint or mitotic checkpoint by preventing premature anaphase onset (PubMed:23187126). Acts by specifically mediating deubiquitination of CDC20, a negative regulator of the anaphase promoting complex/cyclosome (APC/C). Deubiquitination of CDC20 leads to stabilize the MAD2L1-CDC20-APC/C ternary complex (also named mitotic checkpoint complex), thereby preventing premature activation of the APC/C. Promotes association of MAD2L1 with CDC20 and reinforces the spindle assembly checkpoint. Promotes also the deubiquitination of histone H2A and H2B. Recruited to RNF8/RNF168-ubiquitinated chromatin surrounding double stranded breaks (DSBs), promotes hydrolysis of such ubiquitin conjugates, thus negatively regulating protein recruitment to damaged chromatin (By similarity). Participates in nucleotide excision repair (NER) pathway by deubiquitinating DDB2 to prevent its premature degradation so it can remain on damaged chromatin (PubMed:23187126). Promotes FOXP3 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability and increased regulatory T-cell lineage stability. Plays also a positive role in innate immune response to DNA viruses by deubiquitinating STING1, selectively removing its 'Lys-48'-linked polyubiquitin chains and stabilizing it (By similarity).|||Interacts with the N-CoR components TBL1X and TBL1XR1.|||Intron retention.|||Nucleus|||USP44-deficient mice show a significant increase in skin tumors when compared to wild-type mice (PubMed:33937266). In addition, they are prone to development of spontaneous tumors, particularly in the lungs (PubMed:23187126). USP44 loss causes also chromosome mis-segregation and aneuploidy (PubMed:23187126).|||Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination and is degraded by the proteasome.|||Widely expressed. Highly expressed in lung, pancreas, skin, liver, stomach and intestine. http://togogenome.org/gene/10090:Otop2 ^@ http://purl.uniprot.org/uniprot/Q80SX5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the otopetrin family.|||Cell membrane|||Expressed at higher level in stomach, testis and olfactory bulb.|||Proton-selective channel that specifically transports protons into cells. Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes. http://togogenome.org/gene/10090:Ntng1 ^@ http://purl.uniprot.org/uniprot/Q8R4G0 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Detected in the midbrain and the hindbrain regions as early as 12 dpc. In the deep nucleus of the cerebellum, as well as in the inferior colliculus and the thalamic regions, expression is detected at 14 dpc, persists to postnatal day 1 and is down-regulated by postnatal day 12. At 14 dpc, expression is segmented in dorsal thalamus and pretectum in the midbrain and is regulated in a layer-specific manner in the superior colliculus. In the olfactory bulb, expression is detected at 14 dpc, increases by postnatal day 1 and is maintained at a high level through postnatal day 21 and into adulthood.|||Expression is restricted primarily to neurons of the CNS, particularly in the dorsal thalamus, olfactory bulb and inferior colliculus. Isoform 1A and isoform 1D are the major products in adult brain.|||Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels. Promotes neurite outgrowth of both axons and dendrites.|||N-glycosylated.|||The laminin N-terminal domain mediates 1:1 binding to NGL ligand with sub-micromolar affinity. Three NGL-binding loops mediate discrimination for LRRC4C/NGL1 among other NGLs by binding specifically to its LRR repeats. This specificity drives the sorting of a mixed population of molecules into discrete cell surface subdomains (By similarity). http://togogenome.org/gene/10090:Vgf ^@ http://purl.uniprot.org/uniprot/Q0VGU4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with HSPA8 on cell membrane (By similarity). Interacts with C3AR1 (PubMed:25456411). Interacts with C1QBP (By similarity).|||Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Activates GABAergic interneurons which are inhibitory neurons of the nervous system and thereby suppresses presynaptic glutamatergic neurons (By similarity). Stimulates also feeding behavior in an orexin-dependent manner in the hypothalamus (By similarity). Functions as a positive regulator for the activation of orexin neurons resulting in elevated gastric acid secretion and gastric emptying (By similarity).|||Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Suppresses presynaptic glutamatergic neurons connected to vasopressin neurons.|||Plays a role in the regulation of memory formation and depression-related behaviors potentially by influencing synaptic plasticity and neurogenesis. Induces acute and transient activation of the NTRK2/TRKB receptor and subsequent CREB phosphorylation (PubMed:26180209, PubMed:30504797). Induces also insulin secretion in insulinoma cells by increasing intracellular calcium mobilization (PubMed:25917832).|||Secreted|||Secreted multifunctional peptide that interacts with different receptors and thereby plays multiple physiological roles including modulation of energy expenditure, pain, response to stress, gastric regulation as well as lipolysis (PubMed:22289198, PubMed:25456411). Activates the G-protein-coupled receptor C3AR1 via a folding-upon-binding mechanism leading to enhanced lipolysis in adipocytes (PubMed:25456411). Interacts with gC1qR receptor in macrophages and microglia causing increased levels of intracellular calcium and hypersensitivity (By similarity).|||Secreted polyprotein that is packaged and proteolytically processed by prohormone convertases PCSK1 and PCSK2 in a cell-type-specific manner (By similarity). VGF and peptides derived from its processing play many roles in neurogenesis and neuroplasticity associated with learning, memory, depression and chronic pain (PubMed:19863797, PubMed:26180209, PubMed:30504797).|||VGF-deficiency produces a lean, hypermetabolic mouse that is resistant to diet and genetically-induced obesity.|||secretory vesicle http://togogenome.org/gene/10090:Slc46a2 ^@ http://purl.uniprot.org/uniprot/Q8CA03 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. SLC46A family.|||Cell membrane|||Down-regulated by the anti-inflammatory drug methotrexate.|||Endosome membrane|||Expressed on cortical epithelial cells in the thymus. Mainly expressed in the thymic cortex and is highly enriched in SCID thymus. Also expressed in lymph nodes, heart, fetal liver, brain, spleen, intestine and kidney, but not in adult liver, skin, skeletal muscle and lung. Expressed in skin epidermis.|||Glycosylated.|||Highly expressed during fetal thymus development and decreases after day 16.|||Mutant mice are resistant to psoriatic inflammation.|||Proton-coupled transporter that delivers pathogen-associated or danger-associated molecular patterns to cytosolic pattern recognition receptors as part of the innate immune response to microbes or tissue injury (PubMed:28539433, PubMed:34235268, PubMed:37116499). Has selectivity toward muropeptides that contain the amino acid diaminopimelic acid (DAP-type peptidoglycan muropeptides) including Tri-DAP and tracheal toxin (TCT), common in Gram-negative bacteria and Gram-positive bacilli. In the context of immune recognition of skin microbiota, shuttles bacterial muropeptides across the endolysosomal membranes into the cytosol for recognition by NOD1, triggering MYD88-dependent secretion of IL1A and neutrophil recruitment in a pyroptosis-type inflammatory process (PubMed:28539433, PubMed:37116499). To a lesser extent and redundantly, transports muramyl dipeptides derived from most bacterial proteoglycans, eliciting NOD2 receptor activation and downstream inflammatory responses (PubMed:28539433). Postulated to function as an importer of cyclic GMP-AMP dinucleotides (cGAMPs) in monocyte and macrophage cell lineages. Selectively imports cGAMPs derived from pathogenic bacteria such as 3'3'-cGAMP thus providing for differential immune recognition of pathogenic versus commensal bacteria. During tumorigenesis may transport extracellular tumor-derived 2'3'-cGAMP across the plasma membrane of M1-polarized macrophages to activate the anti-tumoral stimulator of interferon genes (STING) pathway (PubMed:34235268). The transport mechanism, its electrogenicity and stoichiometry remain to be elucidated (Probable). http://togogenome.org/gene/10090:Desi1 ^@ http://purl.uniprot.org/uniprot/Q9CQT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DeSI family.|||Cytoplasm|||Homodimer (PubMed:22370726, PubMed:22498933). Interacts with UBQLN4; leading to the export of UBQLN4 from the nucleus (By similarity).|||Nucleus|||Protease which deconjugates SUMO1, SUMO2 and SUMO3 from some substrate proteins (PubMed:22370726, PubMed:22498933). Has isopeptidase but not SUMO-processing activity (PubMed:22370726, PubMed:22498933). Desumoylates ZBTB46 (PubMed:22370726). Collaborates with UBQLN4 in the export of ubiquitinated proteins from the nucleus to the cytoplasm (By similarity). http://togogenome.org/gene/10090:Arrdc4 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1F4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the arrestin family.|||Cell membrane|||Cytoplasmic vesicle|||Early endosome|||Functions as an adapter recruiting ubiquitin-protein ligases to their specific substrates (PubMed:27462458). Plays a role in endocytosis of activated G protein-coupled receptors (GPCRs) (By similarity). Through an ubiquitination-dependent mechanism also plays a role in the incorporation of SLC11A2 into extracellular vesicles (PubMed:27462458). May play a role in glucose uptake (By similarity). Participates in innate immune response by promoting IFIH1/MDA5 activation through interaction with TRIM65 (By similarity).|||Interacts with ADRB2. Interacts (via PPxY motifs) with ITCH, NEDD4L and WWP2. Interacts with AVPR2. Identified in a complex containing at least ARRDC4, AVPR2 and HGS (By similarity). Interacts with SLC11A2; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (PubMed:27462458). Interacts with TRIM65 (By similarity).|||Up-regulated by high iron diet. http://togogenome.org/gene/10090:Plekhb2 ^@ http://purl.uniprot.org/uniprot/Q9QZC7 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Highly expressed at birth and up to day 3; expressed at lower levels in embryo and adult.|||Highly expressed in brain, retina, heart and kidney. Detected at lower levels in lung, muscle and nerve.|||Involved in retrograde transport of recycling endosomes.|||Recycling endosome membrane|||The PH domain specifically binds phosphatidylserine, which is enriched in recycling endosome membranes, it doesn't recognize PIPs. http://togogenome.org/gene/10090:Map2k6 ^@ http://purl.uniprot.org/uniprot/P70236|||http://purl.uniprot.org/uniprot/Q543Z5 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by dual phosphorylation on Ser-207 and Thr-211 in response to a variety of cellular stresses, including UV radiation, osmotic shock, hypoxia, inflammatory cytokines, interferon gamma (IFNG), and less often by growth factors. MAP2K6/MKK6 is activated by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Cytoplasm|||Dimer. Interacts (via its D domain) with its substrates MAPK11, MAPK12, MAPK13 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2. Interacts with DCTN1. Interacts with EIF2AK2/PKR.|||Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.|||MSAPK14 can negatively regulate the stability of the MAP2K6/MKK6 mRNA and thus control the steady-state concentration of one of its upstream activator.|||Nucleus|||The D domain (residues 4-19) contains a conserved docking site and is required for the binding to MAPK substrates.|||The DVD domain (residues 311-334) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation (By similarity).|||Weakly autophosphorylated. Phosphorylated at Ser-207 and Thr-211 by the majority of M3Ks, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2.|||cytoskeleton http://togogenome.org/gene/10090:Camk2a ^@ http://purl.uniprot.org/uniprot/P11798 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.|||Autophosphorylation of Thr-286 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation (By similarity). Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (By similarity). Also regulates the migration of developing neurons (By similarity). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (PubMed:15994560). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (By similarity). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (PubMed:23502535).|||Cytoplasm|||Expressed in brain.|||Expressed in skeletal muscle.|||Has no kinase activity.|||Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7.|||Postsynaptic density|||Synapse|||There are 4 genes encoding calcium/calmodulin-dependent protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The corresponding proteins assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (By similarity). Interacts with BAALC. Interacts with MPDZ. Interacts with SYN1. Interacts with CAMK2N2. Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity). Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2. Interacts with LRRC7. Interacts with GRM5 (By similarity). Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (PubMed:23502535). Interacts with CAMK2N1; this interaction requires CAMK2A activation by Ca(2+) (By similarity).|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Or5aq1b ^@ http://purl.uniprot.org/uniprot/A2AVB8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cmtm1 ^@ http://purl.uniprot.org/uniprot/B7ZP21 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Smgc ^@ http://purl.uniprot.org/uniprot/Q6JHY2 ^@ PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in terminal tubule cells of the submandibular gland (at protein level). Expressed in submandibular salivary glands of 3-day-old males but not adults. Expression in adult submandibular glands is restricted to females. Isoform 5 is expressed in both 3-day-old and adult sublingual glands.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Rbp2 ^@ http://purl.uniprot.org/uniprot/Q059R7|||http://purl.uniprot.org/uniprot/Q08652 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Expressed in prenatal liver, intestine and lung, and in adult intestine.|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Intracellular transport of retinol. http://togogenome.org/gene/10090:Rnase11 ^@ http://purl.uniprot.org/uniprot/Q5GAM9|||http://purl.uniprot.org/uniprot/W0UVF9 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pancreatic ribonuclease family.|||In contrast to other members of the family, lacks the conserved His active site in position 75, suggesting it is inactive.|||Secreted http://togogenome.org/gene/10090:Fgf12 ^@ http://purl.uniprot.org/uniprot/A0A338P752|||http://purl.uniprot.org/uniprot/A0A7U3JW65|||http://purl.uniprot.org/uniprot/P61329|||http://purl.uniprot.org/uniprot/Q3UFZ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Interacts with the C-terminal region of SCN9A.|||Involved in nervous system development and function. Promote neuronal excitability by elevating the voltage dependence of neuronal sodium channel SCN8A fast inactivation.|||Nucleus http://togogenome.org/gene/10090:Or2t29 ^@ http://purl.uniprot.org/uniprot/M9MMK5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Olfml2b ^@ http://purl.uniprot.org/uniprot/Q3V1G4 ^@ PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Broadly expressed. Within the eye, present in ganglion cells, inner nuclear layers, inner segment of photoreceptor layers and retinal pigment epithelium (at protein level).|||Homodimer. Binds to heparin and chondroitin sulfate E.|||O-glycosylated and N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Fign ^@ http://purl.uniprot.org/uniprot/Q9ERZ6 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent microtubule severing protein. Severs microtubules along their length and depolymerizes their ends, primarily the minus-end, suppressing microtubule growth from and attachment to centrosomes. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome (By similarity).|||Belongs to the AAA ATPase family.|||Defects in Fign are characterized by a side-to-side head-shaking and circling behavior, due to reduced or absent semicircular canals. Diseased mice also have small eyes, associated with cell-cycle delay and insufficient growth of the retinal neural epithelium, and lower penetrance skeletal abnormalities, including pelvic girdle dysgenesis, skull bone fusions and polydactyly.|||Expression begins in the embryo at 8.5 dpc. Oocyst, optic cup and pelvic anlage show strongest expression. At 10.5 dpc, expression concentrated in epithelial cells of the dorso-lateral, posterior and anterior otocyst wall. Expression in the eye is found fairly evenly throughout the retinal neural epithelium, with some enrichment in the inner retina where cells begin their differentiation to form retinal ganglion cells. Some expression is seen in the lens pit and in the cell layer that will become the pigment epithelium. At 11.5 dpc, when the superior semicircular canal has begun to form from the posterior otocyst, much of the expression is concentrated there, although there is also expression in the part of the otocyst that will form the lateral or horizontal canal. Strong expression was also seen in the acoustic ganglia and cochlea. In the eye the expression pattern is similar to that found in 10.5 dpc except that expression is concentrated in the retinal ganglion layer. As the lens vesicle forms and matures at 13 dpc, expression is also seen in the anterior wall of the lens, but persists throughout the neural retina, especially in the peripheral retina where cells are still differentiating.|||FIGN and AKAP8 double mutant mice die soon after birth due to cleft palate.|||Interacts with AKAP8 (via C-terminus).|||Nucleus matrix|||Widely expressed.|||centrosome http://togogenome.org/gene/10090:Trnp1 ^@ http://purl.uniprot.org/uniprot/Q80ZI1 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ DNA-binding factor that regulates the expression of a subset of genes and plays a key role in tangential, radial, and lateral expansion of the brain neocortex. Regulates neural stem cells proliferation and the production of intermediate neural progenitors and basal radial glial cells affecting the process of cerebral cortex gyrification. May control the proliferation rate of cells by regulating their progression through key cell-cycle transition points.|||Expressed in brain and kidney (at protein level). Also detected in spleen and intestine.|||Expression is highly restricted to the phase of neurogenesis with high levels in all cells in the ventricular zone (VZ) at 10 dpc. Expression disappears at the end of neurogenesis (18 dpc). However, it remains present in a specific adult neurogenic region with the highest amplification and neuronal output, the subependymal zone of the lateral ventricle from where newborn neurons migrate to the olfactory bulb (at protein level).|||Interacts with TMF1; may regulate TRNP1 proteasomal degradation.|||Nucleus|||Ubiquitinated, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Svil ^@ http://purl.uniprot.org/uniprot/Q3TTX5|||http://purl.uniprot.org/uniprot/Q8K4L3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As opposed to other villin-type headpiece domains, supervillin HP (SVHP) doesn't bind F-actin due to the absence of a conformationally flexible region (V-loop).|||Associates with F-actin (By similarity). Interacts with NEB (By similarity). Interacts with MYH9 (By similarity). Interacts with MYLK (By similarity). Interacts with TASOR (PubMed:31112734).|||Belongs to the villin/gelsolin family.|||Cell membrane|||Cleavage furrow|||Expressed in the heart, tongue and granular cells within the cerebellum.|||Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation. Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function.|||Interacts with TRIP6 (By similarity). Interacts with DYNLT1 (By similarity). Interacts with KIF14; at midbody during cytokinesis (By similarity).|||May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity).|||Midbody|||cytoskeleton|||invadopodium|||podosome http://togogenome.org/gene/10090:Rasl2-9 ^@ http://purl.uniprot.org/uniprot/A6H622|||http://purl.uniprot.org/uniprot/Q61820 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Ran family.|||GTP-binding protein involved in nucleocytoplasmic transport (By similarity). Required for the import of protein into the nucleus and also for RNA export (By similarity). Involved in chromatin condensation and control of cell cycle (By similarity).|||GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle.|||Nucleus|||Testis specific. http://togogenome.org/gene/10090:Lypd1 ^@ http://purl.uniprot.org/uniprot/Q8BLC3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro increases receptor desensitization and decreases affinity for ACh of alpha-4:beta-2-containing nAChRs (PubMed:19246390). May play a role in the intracellular trafficking of alpha-4:beta-2 and alpha-7-containing nAChRs and may inhibit their expression at the cell surface (PubMed:26276394, PubMed:25716842). May be involved in the control of anxiety (PubMed:19246390).|||Cell membrane|||Increased anxiety-like behaviors. Increased glutamatergic activity in response to nicotine in layer V neurons of the medial prefrontal cortex.|||Interacts with CHRNA4 and nAChRs containing alpha-4:beta-2 (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits.|||Preferentially expressed in the nervous system. Expressed in embryonic and postnatal postmitotic central and peripheral neurons including subpopulations of motor neurons, sensory neurons, interneurons and neurons of the autonomous nervous system. Expressed around the growing nerves in the limb bud (PubMed:16236524). Expressed at high levels in specific brain regions such as the prefrontal cortex, amygdala, hippocampus, mediodorsal thalamus, dentate gyrus and specific brainstem nuclei (at protein level) (PubMed:19246390). http://togogenome.org/gene/10090:Ass1 ^@ http://purl.uniprot.org/uniprot/P16460 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by CLOCK in a circadian manner which negatively regulates its enzyme activity. Deacetylated by histone deacetylases.|||Belongs to the argininosuccinate synthase family. Type 1 subfamily.|||Expressed in fetal liver.|||Homotetramer. Interacts with NMRAL1 (By similarity). Interacts with CLOCK; in a circadian manner (PubMed:28985504). Forms tissue-specific complexes with ASL, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or NOS3; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.|||One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues.|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Ap4e1 ^@ http://purl.uniprot.org/uniprot/Q80V94 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). Interacts with TEPSIN (By similarity). Interacts with GRIA2; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (PubMed:18341993).|||Belongs to the adaptor complexes large subunit family.|||Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways. AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ulk4 ^@ http://purl.uniprot.org/uniprot/Q3V129 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.|||Expressed in embryonic and adult brain. In the brain, widely expressed, with highest levels in layers II/III and V of the cortex, piriform cortex, CA1-3 of hippocampus, dentate gyrus, ependymal cells lining the ventricles and choroid plexus, and in the thalamic reticular nucleus (at protein level).|||Knockout mice are smaller than sex-matched littermates, and all exhibit domed heads typical of hydrocephalus. The majority die before reaching 4 months of age. Brain lateral and third ventricles are severaly dilated with frequent hemorrhage, sometimes accompanied by fibrosis and neovascularization of the meninges and choroid. Nasal passages and maxillary sinuses are partially filled with varying combinations of proteinaceous fluid or suppurative exudates. Suppurative otitis media is frequently observed. On the respiratory epithelium and ependymal cells lining the dilated ventricles, cilia are shorter than those in wild-type littermate control mice (PubMed:21746835). Partial agenesis of the corpus callosum has also been reported (PubMed:24284070).|||May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility. http://togogenome.org/gene/10090:Stum ^@ http://purl.uniprot.org/uniprot/A0A1B0GS08|||http://purl.uniprot.org/uniprot/Q0VBF8 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Able to rescue the walking impairment phenotype when transfected in mutant flies lacking the stum protein (AC Q9W2E1).|||Belongs to the SPEC3 family. Stum subfamily.|||Membrane http://togogenome.org/gene/10090:Srms ^@ http://purl.uniprot.org/uniprot/Q0VBH4|||http://purl.uniprot.org/uniprot/Q8BQI4 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. http://togogenome.org/gene/10090:Relt ^@ http://purl.uniprot.org/uniprot/Q8BX43 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RELT family.|||Cell membrane|||Cytoplasm|||Expressed by secretory stage ameloblasts and by odontoblasts at postnatal day 5. It is not detected in maturation stage ameloblasts and only residual expression is observed in odontoblasts by postnatal day 12.|||Expressed in the teeth.|||Interacts with RELL1, RELL2, OXSR1, PLSCR1 and STK39.|||May play a role in apoptosis. Induces activation of MAPK14/p38 and MAPK8/JNK MAPK cascades, when overexpressed. Involved in dental enamel formation (PubMed:30506946).|||Phosphorylated in vitro by OXSR1. Phosphorylated by STK39.|||perinuclear region http://togogenome.org/gene/10090:Or5p6 ^@ http://purl.uniprot.org/uniprot/Q8VG04 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Zswim8 ^@ http://purl.uniprot.org/uniprot/Q3UHH1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZSWIM8 family.|||Component of the SCF-like E3 ubiquitin-protein ligase complex which contains CUL3, RBX1, ELOB, ELOC and ZSWIM8.|||Substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex that promotes target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs) (PubMed:33184237). The SCF-like E3 ubiquitin-protein ligase complex acts by catalyzing ubiquitination and subsequent degradation of AGO proteins (AGO1, AGO2, AGO3 and/or AGO4), thereby exposing miRNAs for degradation (By similarity). Specifically recognizes and binds AGO proteins when they are engaged with a TDMD target (By similarity). May also acts as a regulator of axon guidance: specifically recognizes misfolded ROBO3 and promotes its ubiquitination and subsequent degradation (By similarity).|||cytosol http://togogenome.org/gene/10090:Satl1 ^@ http://purl.uniprot.org/uniprot/Q9D5N8 ^@ Similarity ^@ Belongs to the acetyltransferase family. http://togogenome.org/gene/10090:Zcchc17 ^@ http://purl.uniprot.org/uniprot/Q9ESX4 ^@ Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in liver, brain, heart, kidney testis, stomach, small intestine, skin, thymus, uterus, placenta, spleen, lung and skeletal muscle.|||Interacts with PNN (By similarity). Associates with the 60S ribosomal subunit.|||Less abundant than isoform 1.|||nucleolus http://togogenome.org/gene/10090:Acsm3 ^@ http://purl.uniprot.org/uniprot/Q3UNX5 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (PubMed:11470804). Capable of activating medium-chain fatty acids with a preference for isobutyrate among fatty acids with 2-6 carbon atoms (PubMed:11470804).|||Detected in kidney (at protein level). Detected in kidney proximal tubules and in liver. Detected at low levels in testis, stomach, heart and lung.|||It is uncertain whether Met-1 or Met-3 is the initiator.|||Mitochondrion|||Mitochondrion matrix|||Up-regulated in kidney by androgens. Down-regulated in kidney by estrogens. Levels in kidney are very low in female C57BL/6 mice and in castrated male C57BL/6, 129/SvJ and BALB/c mice. Constitutively expressed in liver. http://togogenome.org/gene/10090:Nup37 ^@ http://purl.uniprot.org/uniprot/Q9CWU9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13 (By similarity).|||Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation (By similarity).|||kinetochore|||nuclear pore complex http://togogenome.org/gene/10090:Psmb6 ^@ http://purl.uniprot.org/uniprot/Q60692 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase T1B family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB6 displays a peptidylglutamyl-hydrolyzing activity also termed postacidic or caspase-like activity, meaning that the peptides bond hydrolysis occurs directly after acidic residues.|||Cytoplasm|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.|||Up-regulated by the antioxidant dithiolethione (D3T) in liver, lung and small intestine (at protein level). http://togogenome.org/gene/10090:Zan ^@ http://purl.uniprot.org/uniprot/E9PWQ7 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Ears2 ^@ http://purl.uniprot.org/uniprot/Q9CXJ1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 1 subfamily.|||Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu).|||Mitochondrion matrix http://togogenome.org/gene/10090:Tas2r106 ^@ http://purl.uniprot.org/uniprot/Q7M724 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Sdr16c5 ^@ http://purl.uniprot.org/uniprot/Q7TQA3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum membrane|||Oxidoreductase with strong preference for NAD. Active in both the oxidative and reductive directions. Oxidizes all-trans-retinol in all-trans-retinaldehyde. No activity was detected with 11-cis-retinol or 11-cis-retinaldehyde as substrates with either NAD(+)/NADH or NADP(+)/NADPH. http://togogenome.org/gene/10090:Zdhhc4 ^@ http://purl.uniprot.org/uniprot/Q9D6H5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DHHC palmitoyltransferase family.|||Cell membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Palmitoyltransferase that could catalyze the addition of palmitate onto protein substrates including the D(2) dopamine receptor DRD2.|||The C-terminal di-lysine motif confers endoplasmic reticulum localization.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Or51b4 ^@ http://purl.uniprot.org/uniprot/F8VQ01 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ciapin1 ^@ http://purl.uniprot.org/uniprot/Q8WTY4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Ana-mors-in' means 'anti-death molecule' in Latin.|||Belongs to the anamorsin family.|||By cytokines such as IL3 and THPO.|||Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1. NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit (By similarity). Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells (PubMed:14970183).|||Cytoplasm|||Death in late gestation due to defective definitive hematopoiesis in the fetal liver, possibly due to initiated apoptosis in erythroid cells during terminal maturation.|||Expressed from early embryogenesis.|||Mitochondrion intermembrane space|||Monomer. Interacts with NDOR1. Interacts with CHCHD4.|||Nucleus|||The C-terminal domain binds 2 Fe-S clusters but is otherwise mostly in an intrinsically disordered conformation.|||The N-terminal domain has structural similarity with S-adenosyl-L-methionine-dependent methyltransferases, but does not bind S-adenosyl-L-methionine. It is required for correct assembly of the 2 Fe-S clusters.|||The twin Cx2C motifs are involved in the recognition by the mitochondrial CHCHD4/MIA40-GFER/ERV1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space. http://togogenome.org/gene/10090:Cpe ^@ http://purl.uniprot.org/uniprot/Q00493|||http://purl.uniprot.org/uniprot/Q543R4 ^@ Cofactor|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Defects in Cpe are the cause of the fat phenotype. Mice homozygous for the fat mutation develop obesity and hyperglycemia that can be suppressed by treatment with exogenous insulin.|||Interacts with Secretogranin III/SCG3.|||Interacts with secretogranin III/SCG3.|||Membrane|||Secreted|||Sorting receptor that directs prohormones to the regulated secretory pathway. Acts also as a prohormone processing enzyme in neuro/endocrine cells, removing dibasic residues from the C-terminal end of peptide hormone precursors after initial endoprotease cleavage.|||secretory vesicle|||secretory vesicle membrane http://togogenome.org/gene/10090:Vmn2r33 ^@ http://purl.uniprot.org/uniprot/K7N705 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:H2ac23 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Nlrp3 ^@ http://purl.uniprot.org/uniprot/Q8R4B8 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NLRP family.|||By activators of Toll-like receptors, such as lipoteichoic acid (LTA) (TLR2), polyinosine-polycytidylic acid (poly(I:C), a synthetic analog of dsRNA) (TLR3) and bacterial lipopolysaccharides (LPS) (TLR4) (PubMed:16546100). Up-regulated by IL2 via STAT5 signaling (PubMed:26098997). Slightly up-regulated in osteoblasts after exposure to invasive, but not invasion-defective, strains of Salmonella typhimurium (at protein level) (PubMed:17907925).|||Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes NLRP3 recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagy-dependent degradation.|||Endoplasmic reticulum|||Expressed with high levels in peripheral blood leukocytes, including Th2 lymphocytes and macrophages (PubMed:15302403, PubMed:26098997, PubMed:16546100, PubMed:28847925). Expressed at low levels in resting osteoblasts (at protein level) (PubMed:17907925).|||Golgi apparatus membrane|||Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (PubMed:26098997). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription (PubMed:26098997). Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3' (PubMed:26098997). May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (PubMed:26098997).|||Inflammasome|||Knockout mice are fertile and appear healthy when housed in a standard specific pathogen-free environment (PubMed:16407890, PubMed:16407888). They do not exhibit any increase in serum IL1B after administration of R837 (an analog to guanosine and TLR7 agonist) and/or LPS (PubMed:16407890, PubMed:16407888, PubMed:37001519). When challenged with LPS, mutant mice are partially resistant to endotoxic shock (PubMed:16407890, PubMed:16546100, PubMed:37001519). Mutant mice display impaired contact hypersensitivity, a T-cell-mediated cellular immune response to repeated epicutaneous exposure to contact allergens, such as trinitrophenylchloride (PubMed:16546100). In response to asbestos inhalation, mice show diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production (PubMed:18403674). In a model of allergic asthma that promotes strictly Th2 responses, mutant animals show less infiltration of eosinophils and lymphocytes into the lungs than their wild-type counterparts, as well as less accumulation of mucus and lymphoid infiltrates (PubMed:26098997). The concentration of Th2 cell-related cytokines, including IL-5 and IL-4, is also lower in lungs from mutant mice compared to wild-type (PubMed:26098997). Knockout mice develop insulin (INS) resistance in response to high-fat diet (PubMed:23809162). Mutants mice are protected from lung injury and cytokine production induced by human SARS coronavirus-2/SARS-CoV-2 N protein (PubMed:34341353).|||Mitochondrion|||Nucleus|||Palmitoylation by ZDHHC12 inhibits the NLRP3 inflammasome by promoting NLRP3 degradation by the chaperone-mediated autophagy pathway. Following palmitoylation, HSPA8/HSC70 recognizes and binds the KFERQ-like motifs on NLRP3 and promotes NLRP3 recruitment to lysosomes, where it is degraded via the chaperone-mediated autophagy pathway in a LAMP2-dependent process.|||Phosphorylation at Ser-194 by MAPK8/JNK1 increases inflammasome activation by promoting deubiquitination by BRCC3 and NLRP3 homooligomerization (PubMed:28943315). Phosphorylation at Ser-803 by CSNK1A1 prevents inflammasome activation by preventing NEK7 recruitment (PubMed:34615873). Phosphorylation at Ser-3 in the pyrin domain inhibits homomultimerization of NLRP3 and activation of the NLRP3 inflammasome: dephosphorylation by protein phosphatase 2A (PP2A) promotes assembly of the NLRP3 inflammasome (PubMed:28465465). Phosphorylation at Ser-291 by PKD/PRKD1 promotes NLRP3 inflammasome assembly (PubMed:28716882). Phosphorylation by ERK1/MAPK3 promotes NLRP3 inflammasome assembly (By similarity). Phosphorylation by BTK (at Tyr-132, Tyr-136, Tyr-145 and Tyr-164) in the region that mediates binding to phosphatidylinositol phosphate, promotes relocalization of NLRP3 and assembly of the NLRP3 inflammasome (PubMed:34554188). Phosphorylation at Tyr-858 inhibits NLRP3 inflammasome assembly: dephosphorylation by PTPN22 promotes inflammasome activation (PubMed:27043286).|||Secreted|||Sensor component of NLRP3 inflammasomes; inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:34861190). The core of NLRP3 inflammasomes consists of a signal sensor component (NLRP3), an adapter (PYCARD/ASC), which recruits an effector pro-inflammatory caspase (CASP1 and, possibly, CASP4 and CASP5) (PubMed:24630723). Homodecamer; inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:34861190, PubMed:35254907). Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:17907925, PubMed:30487600). Interacts (via LRR repeat domain) with NEK7 (via N-terminus); the interaction is required for the formation of the complex NLRP3:PYCARD, oligomerization of PYCARD/ASC and activation of CASP1 (PubMed:26642356, PubMed:26814970, PubMed:26553871, PubMed:34615873, PubMed:37001519). Interacts (via LRR repeat domain) with NR4A1/Nur77 (via N-terminus); the interaction is direct, requires activation of NR4A1 by its ligands NBRE-containing dsDNA and lipopolysaccharide, and stimulates the association of NLRP3 with NEK7 for non-canonical NLRP3 inflammasome activation (PubMed:37001519). Interacts with CARD8; leading to inhibit formation of the NLRP3 inflammasome (By similarity). Interacts with MEFV; this interaction targets NLRP3 to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to specific stimuli (PubMed:22801494). Interacts with GBP5 (via DAPIN domain); this interaction promotes inflammasome assembly in response to microbial and soluble, but not crystalline, agents (By similarity). Interacts with PML (isoform PML-1) (via the leucine-rich repeat (LRR) domain); PML-mediated increase in NLRP3 inflammasome activation does not depend upon this interaction (By similarity). Interacts (via NACHT domain) with DHX33 (via DEAH box); NLRP3 activation in presence of cytosolic dsRNA is mediated by DHX33 (By similarity). Interacts (via NACHT and LRR domains) with ARRB2; this interaction is direct and inducible by polyunsaturated fatty acids (PUFAs) (By similarity). Interacts (via NACHT domain) with DDX3X under both LPS-primed and inflammasome-activating conditions (PubMed:31511697). Interacts with IRF4 (via the LRR domain); this interaction is direct and is required for optimal IRF4 binding to IL4 promoter and efficient IL4 transactivation during differentiation of Th2 helper T-cells (PubMed:26098997). Interacts with MAVS; promoting localization to mitochondria and activation of the NLRP3 inflammasome (PubMed:23582325). Interacts with MARK4; promoting localization of NLRP3 to the microtubule organizing center (MTOC) (PubMed:28656979). Interacts with TRIM50; this interaction promotes also NLRP3 oligomerization and subsequent inflammasome activation (PubMed:36178239). Interacts with IRGM; preventing NLRP3 inflammasome assembly and promoting NLRP3 degradation (By similarity). Interacts (via KFERQ-like motifs) with HSPA8/HSC70; promoting NLRP3 degradation by the chaperone-mediated autophagy pathway (By similarity).|||Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis (PubMed:19362020, PubMed:23582325, PubMed:26814970, PubMed:27929086, PubMed:26642356, PubMed:27374331, PubMed:28847925, PubMed:28656979, PubMed:30518920, PubMed:36178239). In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:19362020, PubMed:16407889, PubMed:18403674, PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925). Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis (PubMed:16546100, PubMed:17008311, PubMed:26814970, PubMed:26642356, PubMed:27374331, PubMed:28847925). Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494). Under resting conditions, ADP-bound NLRP3 is autoinhibited (By similarity). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407888, PubMed:16407890, PubMed:16407889, PubMed:18403674, PubMed:19362020, PubMed:37001519). Almost all stimuli trigger intracellular K(+) efflux (PubMed:23809161). These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex (PubMed:26814970, PubMed:34615873, PubMed:34861190). Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600). Shows ATPase activity (PubMed:34861190).|||The FISNA domain is a critical mediator of NLRP3 conformational during NLRP3 activation. It becomes ordered in its key regions during activation to stabilize the active NACHT conformation and mediate most interactions in the NLRP3 disk.|||The KFERQ-like motifs mediate binding to HSPA8/HSC70 following NLRP3 paylmitoylation by ZDHHC12.|||The LRR domain mediates the interaction with IRF4, PML, NEK7 and NR4A1/Nur77.|||The disulfide bond in the pyrin domain might play a role in reactive oxygen species-mediated activation.|||The pyrin domain (also called DAPIN domain or PYD) is involved in PYCARD/ASC-binding.|||Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:23246432). Ubiquitination does not lead to degradation, but inhibits inflammasome activation (PubMed:23246432). Deubiquitination is catalyzed by BRCC3 and associated with NLRP3 activation and inflammasome assembly (PubMed:23246432). This process can be induced by the activation of Toll-like receptors (by LPS), through a non-transcriptional pathway dependent on the mitochondrial production of reactive oxygen species, and by ATP (PubMed:22948162). Ubiquitinated by TRIM31 via 'Lys-48'-linked ubiquitination, leading to its degradation by the proteasome (PubMed:27929086). Ubiquitinated at Lys-687 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity). Ubiquitinated by TRIM35 via 'lys-48' and 'Lys-63'-linked ubiquitination leading to inhibition of NLRP3 inflammasome activation (By similarity).|||Under resting conditions, NLRP3 binds ADP and is autoinhibited (By similarity). Inactive NLRP3 forms homodecameric double-ring cages that hide pyrin domains within NACHT-LRR rings to avoid premature activation (PubMed:30518920, PubMed:34861190, PubMed:35254907). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18403674, PubMed:19362020). Almost all stimuli trigger intracellular K(+) efflux (PubMed:23809161). These stimuli lead to membrane perturbations that induce activation of NLRP3 (PubMed:34861190). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and recruitment of PYCARD/ASC for the formation of an active inflammasome complex (PubMed:26814970, PubMed:26642356, PubMed:28716882, PubMed:30487600, PubMed:34615873, PubMed:34861190). NEK7-activated NLRP3 forms a disk-shaped inflammasome (By similarity). NLRP3 and PYCARD/ASC interact via their respective pyrin domains; interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (PubMed:24630723). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (By similarity). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (By similarity). NLRP3 inflammasome assembly is inhibited by IRGM, which impedes NLRP3 oligomerization (By similarity). Specifically inhibited by sulfonylurea MCC950 (also named CP-456,773, CRID3), a potent and specific small-molecule inhibitor of the NLRP3 inflammasome that acts by preventing ATP hydrolysis (PubMed:35254907).|||Up-regulated during CD4(+) T-lymphocyte differentiation, in Th0, Th1 and Th2 cells. Not detected in naive CD4(+) T-lymphocytes (at protein level).|||cytosol|||microtubule organizing center http://togogenome.org/gene/10090:Ahcyl2 ^@ http://purl.uniprot.org/uniprot/F8WGT1|||http://purl.uniprot.org/uniprot/F8WI65|||http://purl.uniprot.org/uniprot/Q68FL4 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adenosylhomocysteinase family.|||Binds 1 NAD(+) per subunit.|||Cytoplasm|||Highly expressed in cerebrum, cerebellum and kidney. Also expressed in thymus, spleen, testis, ovary and, at lower, levels in lung and liver (at protein level). In cerebellum, expressed in interneurons.|||Homotetramer. Forms heteromultimers with AHCYL1 (via the C-terminal region). Interacts with ITPR1; with lower affinity than AHCYL1 and maybe via ITPR1. Interacts with SLC4A4. Interacts with ZCCHC4 (By similarity).|||May regulate the electrogenic sodium/bicarbonate cotransporter SLC4A4 activity and Mg(2+)-sensitivity. On the contrary of its homolog AHCYL1, does not regulate ITPR1 sensitivity to inositol 1,4,5-trisphosphate.|||Microsome|||Phosphorylated during neuronal differentiation at the LISN domain. http://togogenome.org/gene/10090:Or5l13 ^@ http://purl.uniprot.org/uniprot/A2AVC3|||http://purl.uniprot.org/uniprot/Q8VG81 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Spib ^@ http://purl.uniprot.org/uniprot/O35906 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Can form homotypic interactions (By similarity). Interacts with IRF4/Pip (By similarity). Interacts with JUN (By similarity). Interacts with TBP (By similarity). May also interact with CREBBP and EP300 (By similarity). Interacts with NONO/p54(nrb) (PubMed:8626664).|||Expressed in the medulla of the thymus, the spleen and germinal centers of the lymph nodes. Expressed in B-cells and T-cells, expression increases during B-cell maturation and decreases during T-cell maturation.|||Nucleus|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform IA.|||Sequence specific transcriptional activator which binds to the PU-box, a purine-rich DNA sequence (5'-GAGGAA-3') that can act as a lymphoid-specific enhancer. Promotes development of plasmacytoid dendritic cells (pDCs), also known as type 2 DC precursors (pre-DC2) or natural interferon (IFN)-producing cells. These cells have the capacity to produce large amounts of interferon and block viral replication. Required for B-cell receptor (BCR) signaling, which is necessary for normal B-cell development and antigenic stimulation.|||The protein contains a weakly acidic N-terminal transactivation domain (TAD) followed by a second TAD rich in proline, serine and threonine. Each of these domains may be required for transcriptional activation of a subset of target genes (By similarity). http://togogenome.org/gene/10090:Cap2 ^@ http://purl.uniprot.org/uniprot/Q9CYT6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CAP family.|||Cell membrane|||May have a regulatory bifunctional role. http://togogenome.org/gene/10090:Sccpdh ^@ http://purl.uniprot.org/uniprot/Q8R127 ^@ Similarity ^@ Belongs to the saccharopine dehydrogenase family. http://togogenome.org/gene/10090:Arhgef18 ^@ http://purl.uniprot.org/uniprot/Q6P9R4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. May play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. Also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells.|||Apical cell membrane|||Cell membrane|||Cytoplasm|||Interacts with SEPT9; interaction may inhibit GEF activity. Interacts with Gbetagamma subunits GNB1 and GNG2 (By similarity). Interacts with EPB41L4B. Interacts with PATJ (via C-terminus).|||cytoskeleton http://togogenome.org/gene/10090:Calr3 ^@ http://purl.uniprot.org/uniprot/Q8BL82|||http://purl.uniprot.org/uniprot/Q9D9Q6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calreticulin family.|||CALR3 capacity for calcium-binding may be absent or much lower than that of CALR (By similarity). During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3. Required for sperm fertility.|||Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5.|||Defective sperm migration from the uterus into the oviduct and defective binding to the zona pellucida.|||Endoplasmic reticulum lumen|||Testis specific, absent in mature sperm. http://togogenome.org/gene/10090:Xkr9 ^@ http://purl.uniprot.org/uniprot/Q5GH62 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated upon caspase cleavage to generate the XK-related protein 9, processed form (PubMed:25231987). Does not act prior the onset of apoptosis (PubMed:25231987).|||Belongs to the XK family.|||Cell membrane|||Highly expressed in the small intestines; weakly expressed in the pancreas, liver, stomach, and large intestines.|||Phospholipid scramblase that promotes phosphatidylserine exposure on apoptotic cell surface (PubMed:25231987). Phosphatidylserine is a specific marker only present at the surface of apoptotic cells and acts as a specific signal for engulfment (PubMed:25231987).|||Undergoes proteolytic processing by caspase-3 (CASP3), caspase-6 (CASP6) and caspase-7 (CASP7) to generate the XK-related protein 9, processed form, leading to its activation. http://togogenome.org/gene/10090:Rabgap1l ^@ http://purl.uniprot.org/uniprot/A6H6A9 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contaminating sequence. Potential poly-A sequence.|||Early endosome|||Expressed in embryonic heart and liver, and in hemopoietic cells (PubMed:10585558). Expressed in the corpus callosum in the central nervous system (CNS) and costameres in skeletal muscle at postnatal day (PND) 30 (PubMed:27718357).|||GTP-hydrolysis activating protein (GAP) for small GTPase RAB22A, converting active RAB22A-GTP to the inactive form RAB22A-GDP (By similarity). Plays a role in endocytosis and intracellular protein transport. Recruited by ANK2 to phosphatidylinositol 3-phosphate (PI3P)-positive early endosomes, where it inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (PubMed:27718357).|||Golgi apparatus|||Interacts (via Rab-GAP TBC domain) with ANK2 (via death domain).|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site. http://togogenome.org/gene/10090:1700013H16Rik ^@ http://purl.uniprot.org/uniprot/Q9DAC5 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Or6ae1 ^@ http://purl.uniprot.org/uniprot/Q8VGL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp664 ^@ http://purl.uniprot.org/uniprot/Q4VA44 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Sfxn1 ^@ http://purl.uniprot.org/uniprot/Q99JR1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Amino acid transporter importing serine, an essential substrate of the mitochondrial branch of the one-carbon pathway, into mitochondria. Mitochondrial serine is then converted to glycine and formate, which exits to the cytosol where it is used to generate the charged folates that serve as one-carbon donors. May also transport other amino acids including alanine and cysteine.|||Belongs to the sideroflexin family.|||Defects in Sfxn1 are the cause of a transitory hypochromic, microcytic anemia characterized by a large number of siderocytes containing non-heme iron granules (PubMed:11274051). The anemia begins at 12 dpc, is most intense at 15 dpc and is still severe at birth, but disappears by 2 weeks of age (PubMed:11274051). Mutant adults are no longer anemic, but they have an impaired response to hemopoietic stress (PubMed:11274051). Most homozygotes also have flexed tails and a belly spot (PubMed:11274051).|||Mitochondrion inner membrane|||Very high levels in the liver during the period of embryonic hepatic hemopoiesis.|||Widely expressed, with highest expression in kidney and liver. http://togogenome.org/gene/10090:Exoc3 ^@ http://purl.uniprot.org/uniprot/Q6KAR6|||http://purl.uniprot.org/uniprot/Q8K0E2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC6 family.|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Cytoplasm|||Golgi apparatus|||It is uncertain whether Met-1 or Met-11 is the initiator.|||Midbody|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8 (By similarity). Interacts with EXOC3L1 (PubMed:18480549). Interacts with BIRC6/bruce (By similarity). Interacts with MYRIP (PubMed:17827149). Interacts with SLC6A9 (By similarity).|||growth cone|||neuron projection|||perinuclear region http://togogenome.org/gene/10090:Cep350 ^@ http://purl.uniprot.org/uniprot/E9Q309 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of a ternary complex that contains CEP350, CEP43 and MAPRE1. Interacts (via C-terminus) directly with CEP43 (via N-terminus). Interacts with NR1H3, PPARA, PPARD and PPARG. Interacts directly with microtubules. Interacts with the fusion protein CEP43-FGFR1, and by doing so recruits and activates PI3K and PLC-gamma. Interacts with CYLD (By similarity). Interacts with CFAP157 (PubMed:27965440). Interacts with CEP19 (via C-terminus) (By similarity).|||Phosphorylated during mitosis.|||Plays an essential role in centriole growth by stabilizing a procentriolar seed composed of at least, SASS6 and CENPJ. Required for anchoring microtubules to the centrosomes and for the integrity of the microtubule network. Recruits PPARA to discrete subcellular compartments and thereby modulates PPARA activity. Required for ciliation.|||centriole|||centrosome|||cilium basal body|||spindle http://togogenome.org/gene/10090:Pde5a ^@ http://purl.uniprot.org/uniprot/Q8CG03 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.|||Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc.|||Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain which contains two homologous allosteric cGMP-binding regions, A and B.|||Phosphorylation is regulated by binding of cGMP to the two allosteric sites. Phosphorylation by PRKG1 leads to its activation.|||Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP. Specifically regulates nitric-oxide-generated cGMP. http://togogenome.org/gene/10090:2200002J24Rik ^@ http://purl.uniprot.org/uniprot/Q9D807 ^@ Similarity ^@ Belongs to the CD225/Dispanin family. http://togogenome.org/gene/10090:Pfkfb2 ^@ http://purl.uniprot.org/uniprot/B2Z892|||http://purl.uniprot.org/uniprot/B2Z893|||http://purl.uniprot.org/uniprot/P70265|||http://purl.uniprot.org/uniprot/Q6GTL7|||http://purl.uniprot.org/uniprot/Q8CDS6 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Highest levels in kidney; also found in heart, brain, spleen, lung, liver, skeletal muscle and testis.|||Homodimer (By similarity). Forms a heterodimer with PFKFB3 (By similarity).|||In the C-terminal section; belongs to the phosphoglycerate mutase family.|||Phosphorylation by AMPK stimulates activity.|||Phosphorylation results in the activation of the kinase activity.|||Synthesis and degradation of fructose 2,6-bisphosphate. http://togogenome.org/gene/10090:Slc2a8 ^@ http://purl.uniprot.org/uniprot/Q9JIF3 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||High expression in blastocysts.|||Highest level of expression in placenta and testis. Highly expressed in adult and pubertal testis, but not prepubertal testis. Lower levels of expression in brain, liver, heart, kidney, fat and skeletal muscle.|||Inhibited by cytochalasin B.|||Inhibited under glucose deprivation.|||Insulin-regulated facilitative hexose transporter that mediates the transport of glucose and fructose (PubMed:10821868, PubMed:10860996, PubMed:23396969). Facilitates hepatic influx of dietary trehalose, which in turn inhibits glucose and fructose influx triggering a starvation signal and hepatic autophagy through activation of AMPK and ULK1 (PubMed:27922102). Also able to mediate the transport of dehydroascorbate (PubMed:23396969).|||Interacts with AP2B1 (PubMed:16723738). Also able to mediate the transport of dehydroascorbate (PubMed:23396969). http://togogenome.org/gene/10090:Cd69 ^@ http://purl.uniprot.org/uniprot/P37217 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By the activation of T-lymphocytes.|||Constitutive Ser/Thr phosphorylation in both mature thymocytes and activated T-lymphocytes.|||Earliest inducible cell surface glycoprotein acquired during lymphoid activation.|||Expressed on the surface of activated T-cells, B-cells, natural killer cells, neutrophils and platelets.|||Homodimer; disulfide-linked.|||Involved in lymphocyte proliferation and functions as a signal transmitting receptor in lymphocytes, natural killer (NK) cells, and platelets.|||Membrane http://togogenome.org/gene/10090:Or2l5 ^@ http://purl.uniprot.org/uniprot/Q8VGJ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppp2r5b ^@ http://purl.uniprot.org/uniprot/Q6PD28 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As the regulatory component of the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme, modulates substrate specificity, subcellular localization, and responsiveness to phosphorylation. The phosphorylated form mediates the interaction between PP2A and AKT1, leading to AKT1 dephosphorylation.|||Belongs to the phosphatase 2A regulatory subunit B56 family.|||Component of the serine/threonine-protein phosphatase 2A complex (PP2A). This complex consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant scaffold subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1. Interacts with AKT1.|||Cytoplasm|||Ubiquitinated by CUL3-KLHL15 complex; this modification leads to proteasomal degradation. http://togogenome.org/gene/10090:Slc39a13 ^@ http://purl.uniprot.org/uniprot/B2RQ45|||http://purl.uniprot.org/uniprot/Q8BZH0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZIP transporter (TC 2.A.5) family.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Functions as a zinc transporter transporting Zn(2+) from the Golgi apparatus to the cytosol and thus influences the zinc level at least in areas of the cytosol (PubMed:18985159). May regulate beige adipocyte differentiation (PubMed:28854265).|||Golgi apparatus membrane|||Highly expressed in some tissues such as bone and eye (PubMed:18985159). Expressed in osteoblasts of tibia and of alveolar bone, in proliferative zone of growth plate, and in odontoblasts on the forming of the dentine of crown in molar tooth (PubMed:18985159). Also expressed fibroblasts in reticular layer of dermis of skin (PubMed:18985159).|||Homodimer.|||Homozygous knockout mice for Slc39a13 show growth retardation and results in a generalized skeletal and connective tissue disorder, namely develop progressive kyphosis after 3 or 4 weeks of age.|||Membrane http://togogenome.org/gene/10090:Ppp1r12c ^@ http://purl.uniprot.org/uniprot/Q3UMT1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, and one or several targeting or regulatory subunits. PPP1R12C mediates binding to myosin. Interacts via its N-terminus with PPP1CB. Interacts with IL16. Interacts with the coiled-coil domain of MPRIP. Interacts with NOD2 (By similarity).|||Phosphorylation at Thr-560 is essential for its interaction with PPP1CB.|||Regulates myosin phosphatase activity.|||stress fiber http://togogenome.org/gene/10090:Timm17a ^@ http://purl.uniprot.org/uniprot/Q545U2|||http://purl.uniprot.org/uniprot/Q9Z0V8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tim17/Tim22/Tim23 family.|||Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50.|||Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50. The complex interacts with the TIMM44 component of the PAM complex. The complex also interacts with DNAJC15 (By similarity).|||Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cltc ^@ http://purl.uniprot.org/uniprot/Q68FD5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the clathrin heavy chain family.|||Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Plays a role in early autophagosome formation.|||Clathrin triskelions, composed of 3 heavy chains and 3 light chains, are the basic subunits of the clathrin coat (By similarity). In the presence of light chains, hub assembly is influenced by both the pH and the concentration of calcium (By similarity). Interacts with HIP1 (By similarity). Interacts with DENND1A, DENND1B and DENND1C (By similarity). Interacts with ERBB2 (By similarity). Interacts with FKBP6 (By similarity). Interacts with OCRL (PubMed:20133602). Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions; TACC3 and CLTC are proposed to form a composite microtubule interaction surface (By similarity). Plays a role in early autophagosome formation (By similarity). Interacts with ATG16L1 (via N-terminus) (By similarity). Interacts with RFTN1; the interaction occurs in response to pathogens (By similarity). Interacts with USP2 isoform 2 (PubMed:26756164). Interacts with TMEM106B (via N-terminus) (By similarity).|||Cytoplasmic vesicle membrane|||Melanosome|||The N-terminal seven-bladed beta-propeller is formed by WD40-like repeats, and projects inward from the polyhedral outer clathrin coat. It constitutes a major protein-protein interaction node (By similarity).|||coated pit|||spindle http://togogenome.org/gene/10090:Meig1 ^@ http://purl.uniprot.org/uniprot/Q61845 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the MEIG1 family.|||Detected in the fetal ovary and testis (PubMed:20339383). Detected in the testes as early as 6 days after birth, expression increases during the first wave of spermatogenesis (PubMed:19805151).|||Essential for spermiogenesis.|||Expressed in the testes (at protein level) (PubMed:1390336, PubMed:35547804, PubMed:20339383). Expressed in the ovary (PubMed:20339383). Several isoforms have been identified differing in their 5'-untranslated exons. These isoforms show different tissue expression (PubMed:19805151). Some are expressed in various tissues, including lung, liver, brain, testis, oviduct and oocytes (PubMed:19805151). Some are testis-specific (PubMed:19805151).|||Interacts with PACRG. Interacts with MORN3 (PubMed:25248657).|||Mice are viable, but males are sterile, producing only a few sperm that are morphologically abnormal. Spermatogenesis is dramatically impaired at the stage of elongation and condensation. Spermatozoa exhibit failure of flagellar formation, disorganization of sperm axonemes and deformed heads. http://togogenome.org/gene/10090:Zfp69 ^@ http://purl.uniprot.org/uniprot/A2A761 ^@ Function|||Polymorphism|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||New Zealand obese (NZO) mice carry a loss-of-function mutation due to the integration of the retrotransposon IAPLTR1 in intron 3 which generates a truncated mRNA lacking both the KRAB and the C2H2 domains. This strain is less diabetes prone (NZO).|||Nucleus|||Putative transcription factor that appears to regulate lipid metabolism. http://togogenome.org/gene/10090:Rhag ^@ http://purl.uniprot.org/uniprot/A0A3B2WBH6|||http://purl.uniprot.org/uniprot/Q9QUT0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.|||Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane. Heterotrimer with RHCE (RHAG)2(RHCE), that transports ammonium and its related derivative methylammonium, in both neutral and ionic forms, across the erythrocyte membrane (PubMed:19807729). The transport of NH4(+) is electrogenic and masks the NH3 transport. Also, may act as a CO2 channel. Moreover in erythrocyte, regulates RHD membrane expression and is associated with rhesus blood group antigen expression (By similarity).|||Glycosylated.|||Homodimer. Heterotrimer; a RHCE monomer interacts with a RHAG homodimer. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with GYPB (via the N-terminal); this interaction bridges the (RHAG)2(RHCE) heterotrimer with the SLC4A1 Band 3 I dimer complexed with GYPA.|||Homozygous knockout mice lacking Rhag exhibit normal growth, development and fertility (PubMed:16581281, PubMed:19807729). Mice exhibit no significant change in body weight and body mass index (PubMed:19807729).|||Membrane http://togogenome.org/gene/10090:Psmb1 ^@ http://purl.uniprot.org/uniprot/O09061|||http://purl.uniprot.org/uniprot/Q6RI64 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1B family.|||Component of the proteasome complex.|||Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.|||Cytoplasm|||Detected in liver (at protein level).|||Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Interacts with SERPINB2 (By similarity). Interacts with RFPL4A (PubMed:12525704). http://togogenome.org/gene/10090:Trmt10b ^@ http://purl.uniprot.org/uniprot/Q9D075 ^@ Function|||Similarity ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily. TRM10 family.|||S-adenosyl-L-methionine-dependent guanine N(1)-methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 (m1G9) in tRNAs. Probably not able to catalyze formation of N(1)-methyladenine at position 9 (m1A9) in tRNAs. http://togogenome.org/gene/10090:Rad51d ^@ http://purl.uniprot.org/uniprot/B1ARD4|||http://purl.uniprot.org/uniprot/B5LBC4|||http://purl.uniprot.org/uniprot/O55230|||http://purl.uniprot.org/uniprot/Q3UGT8|||http://purl.uniprot.org/uniprot/Q9EP85 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RecA family. RAD51 subfamily.|||Highly expressed in brain followed by testis. Also expressed in heart, liver, kidney, spleen, lung and skeletal muscle.|||Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Bind to single-stranded DNA (ssDNA) and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. Involved in telomere maintenance. The BCDX2 subcomplex XRCC2:RAD51D can stimulate Holliday junction resolution by BLM (By similarity).|||Midgestation lethal.|||Nucleus|||Part of the BCDX2 complex consisting of RAD51B, RAD51C, RAD51D and XRCC2; the complex has a ring-like structure arranged into a flat disc around a central channel. In the absence of DNA, the BCDX2 subcomplex XRCC2:RAD51D formed a multimeric ring structure; in the presence of single-stranded DNA it formed a filamentous structure with the ssDNA. Interacts with SWSAP1 and ZSWIM7; involved in homologous recombination repair. Interacts with BLM; required for stimulation of BLM activity by the BCDX2 subcomplex XRCC2:RAD51D (By similarity).|||telomere http://togogenome.org/gene/10090:Arhgef5 ^@ http://purl.uniprot.org/uniprot/E9Q7D5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activation of SRC induces tyrosine phosphorylation of ARHGEF5.|||Chemotaxis of macrophages, T and B lymphocytes and bone marrow-derived mature dendritic cells from mutant mice is not affected but chemotaxis of immature dendritic cells is abolished.|||Cytoplasm|||Guanine nucleotide exchange factor which activates Rho GTPases (PubMed:19713215, PubMed:21525037). Strongly activates RHOA (PubMed:19713215, PubMed:21525037). Also strongly activates RHOB, weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ or RAC1 (PubMed:19713215). Involved in regulation of cell shape and actin cytoskeletal organization (PubMed:21525037). Plays a role in actin organization by generating a loss of actin stress fibers and the formation of membrane ruffles and filopodia (By similarity). Required for SRC-induced podosome formation (PubMed:21525037). Involved in positive regulation of immature dendritic cell migration (PubMed:19713215).|||Interacts with SRC (PubMed:21525037). Forms a ternary complex with SRC and the PI3K 85 kDa subunit (PubMed:21525037). Interacts with and is activated by the heterodimer formed by GNB1 and GNG2 (PubMed:19713215). Interacts with ODAM (via C-terminus) (By similarity). Interacts with RHOA (PubMed:19713215).|||Nucleus|||The PH domain binds to phosphoinositides and is essential for podosome formation.|||podosome http://togogenome.org/gene/10090:Csnk1g2 ^@ http://purl.uniprot.org/uniprot/Q8BVP5|||http://purl.uniprot.org/uniprot/Q99K78 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated by aPKC which promotes dissociation from the cell cortex.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.|||Cytoplasm|||Expressed in both the striatum and the neocortex.|||Monomer (By similarity). Interacts with MTA1 (short isoform) in the cytoplasm (PubMed:15077195). Interacts with SMAD3 (By similarity). Interacts with DUOXA2 (By similarity).|||Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling (By similarity). Phosphorylates MTA1 (PubMed:15077195). Phosphorylates COL4A3BP/CERT and SMAD3. SMAD3 phosphorylation promotes its ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Hyperphosphorylation of the serine-repeat motif of COL4A3BP/CERT leads to its inactivation by dissociation from the Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide and sphingomyelin synthesis. Triggers PER1 proteasomal degradation probably through phosphorylation (By similarity). Involved in brain development and vesicular trafficking and neurotransmitter releasing from small synaptic vesicles. Regulates fast synaptic transmission mediated by glutamate (PubMed:16014721). Involved in regulation of reactive oxygen species (ROS) levels (By similarity).|||Stimulated by estrogen.|||The phospho-regulated basic and hydrophobic (PRBH) motif is sufficient and important for interaction with phospholipids permitting cortical localization. Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane.|||cell cortex http://togogenome.org/gene/10090:Birc5 ^@ http://purl.uniprot.org/uniprot/O70201 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-129 results in its homodimerization, while deacetylation promotes the formation of monomers which heterodimerize with XPO1/CRM1 which facilitates its nuclear export. The acetylated form represses STAT3 transactivation. The dynamic equilibrium between its acetylation and deacetylation at Lys-129 determines its interaction with XPO1/CRM1, its subsequent subcellular localization, and its ability to inhibit STAT3 transactivation.|||Belongs to the IAP family.|||Chromosome|||Cytoplasm|||In vitro phosphorylation at Thr-117 by AURKB prevents interaction with INCENP and localization to mitotic chromosomes. Phosphorylation at Thr-48 by CK2 is critical for its mitotic and anti-apoptotic activities. Phosphorylation at Thr-34 by CDK15 is critical for its anti-apoptotic activity.|||Midbody|||Monomer or homodimer. Exists as a homodimer in the apo state and as a monomer in the CPC-bound state. The monomer protects cells against apoptosis more efficiently than the dimer. Only the dimeric form is capable of enhancing tubulin stability in cells. When phosphorylated, interacts with LAMTOR5/HBXIP; the resulting complex binds pro-CASP9, as well as active CASP9, but much less efficiently. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and CDCA8. Interacts with JTB. Interacts (via BIR domain) with histone H3 phosphorylated at 'Thr-3' (H3pT3). Interacts with EVI5. Interacts with GTP-bound RAN in both the S and M phases of the cell cycle. Interacts with USP9X. Interacts with tubulin. Interacts with BIRC2/c-IAP1. The acetylated form at Lys-129 interacts with STAT3. The monomeric form deacetylated at Lys-129 interacts with XPO1/CRM1. The monomeric form interacts with XIAP/BIRC4. Both the dimeric and monomeric form can interact with DIABLO/SMAC. Interacts with BIRC6/bruce. Interacts with FBXL7; this interaction facilitates the polyubiquitination and subsequent proteasomal degradation of BIRC5 by the SCF(FBXL7) E3 ubiquitin-protein ligase complex (By similarity).|||Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:25778398). Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (By similarity). Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (By similarity). Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (By similarity). The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (By similarity). May counteract a default induction of apoptosis in G2/M phase (By similarity). The acetylated form represses STAT3 transactivation of target gene promoters (By similarity). May play a role in neoplasia. Inhibitor of CASP3 and CASP7 (By similarity). Essential for the maintenance of mitochondrial integrity and function (PubMed:25778398).|||Nucleus|||The BIR repeat is necessary and sufficient for LAMTOR5 binding.|||Ubiquitinated by the Cul9-RING ubiquitin-protein ligase complex, leading to its degradation. Ubiquitination is required for centrosomal targeting. Deubiquitinated by USP35 or USP38; leading to stabilization.|||centromere|||kinetochore|||spindle http://togogenome.org/gene/10090:Cyp27b1 ^@ http://purl.uniprot.org/uniprot/O35084|||http://purl.uniprot.org/uniprot/Q66JY8 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis. Catalyzes the rate-limiting step in the activation of vitamin D in the kidney, namely the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1-alpha position to form the hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3/calcitriol that acts via the vitamin D receptor (VDR) (PubMed:15972816, PubMed:10092858). Has 1-alpha-hydroxylase activity on vitamin D intermediates of the CYP24A1-mediated inactivation pathway. Converts 24R,25-dihydroxyvitamin D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR. Also active on 25-hydroxyvitamin D2 (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:15972816, PubMed:10092858).|||Activated by cardiolipin and dioleoyl phosphatidylethanolamine (DOPE), phospholipids found in the inner mitochondrial membrane. Inhibited by high substrate concentration.|||Belongs to the cytochrome P450 family.|||Kidney.|||Mitochondrion membrane http://togogenome.org/gene/10090:Arhgap25 ^@ http://purl.uniprot.org/uniprot/Q8BYW1 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Arl5c ^@ http://purl.uniprot.org/uniprot/Q6P068 ^@ Function|||Similarity ^@ Belongs to the small GTPase superfamily. Arf family.|||Binds and exchanges GTP and GDP. http://togogenome.org/gene/10090:AI593442 ^@ http://purl.uniprot.org/uniprot/Q32M26 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Trim43b ^@ http://purl.uniprot.org/uniprot/P86448 ^@ Developmental Stage|||Similarity ^@ Belongs to the TRIM/RBCC family.|||Expression is restricted to preimplantation embryos and peaks at the 8-cell to morula stage. http://togogenome.org/gene/10090:Far2 ^@ http://purl.uniprot.org/uniprot/Q7TNT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acyl-CoA reductase family.|||Catalyzes the reduction of saturated but not unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols. A lower activity can be observed with shorter fatty acyl-CoA substrates (PubMed:15220348). It may play a role in the production of ether lipids/plasmalogens and wax monoesters which synthesis requires fatty alcohols as substrates (By similarity).|||Peroxisome membrane|||Specifically expressed in the meibomian glands of the eyelid and the sebaceous glands of the skin. Also expressed in the brain where large quantities of ether lipids are synthesized. http://togogenome.org/gene/10090:Aox2 ^@ http://purl.uniprot.org/uniprot/Q5SGK3 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:23263164).|||Belongs to the xanthine dehydrogenase family.|||Binds 1 FAD per subunit.|||Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Binds 2 [2Fe-2S] clusters per subunit.|||Cytoplasm|||Expressed in olfactory mucosa epithelium (at protein level). Detected in skin.|||Homodimer.|||Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as phthalazine, as well as aldehydes, such as benzaldehyde and retinal. Cannot use hypoxanthine as substrate. http://togogenome.org/gene/10090:Atl2 ^@ http://purl.uniprot.org/uniprot/E9QND8|||http://purl.uniprot.org/uniprot/Q6PA06|||http://purl.uniprot.org/uniprot/Q8BYP9|||http://purl.uniprot.org/uniprot/Q9D873 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Endoplasmic reticulum membrane|||GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis.|||Interacts with REEP5 and RTN3 (PubMed:19665976). Interacts with ZFYVE27 (By similarity). http://togogenome.org/gene/10090:Coro1a ^@ http://purl.uniprot.org/uniprot/O89053|||http://purl.uniprot.org/uniprot/Q3U1N0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat coronin family.|||Binds actin.|||Expressed in spleen, lymph nodes, thymus, brain and at very lower levels in lung. Also expressed in cells of the lymphoid/myeloid lineage. Not expressed in Kuffper cells.|||May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes.|||Membrane|||Polyubiquitinated by RNF128 with 'Lys-48'-linked chains, leading to proteasomal degradation.|||cell cortex|||cytoskeleton|||phagosome membrane|||phosphorylation at Ser-412 by PKC strongly down-regulates the association with actin. http://togogenome.org/gene/10090:Hnrnpc ^@ http://purl.uniprot.org/uniprot/Q9Z204 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM HNRPC family. RALY subfamily.|||Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules. Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides. May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing.|||Nucleus|||Phosphorylated on Ser-268 and Ser-306 in resting cells.|||Sumoylated. Sumoylation reduces affinity for mRNA.|||Tetramer composed of 3 copies of isoform C1 and 1 copy of isoform C2. Assembly of 3 tetramers with bound pre-mRNA gives rise to a 19S complex that interacts with HNRNPA2B1 tetramers. Component of the 40S hnRNP particle. Identified in the spliceosome C complex. Interacts with IGF2BP1. Interacts with DHX9; this interaction is direct, enhanced probably by their concomitant binding to RNA and mediates the attachment to actin filaments (By similarity). Interacts with PPIA/CYPA (By similarity). http://togogenome.org/gene/10090:Jph1 ^@ http://purl.uniprot.org/uniprot/Q9ET80 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the junctophilin family.|||Cell membrane|||Endoplasmic reticulum membrane|||Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes.|||Mice are unable to suckle probably due to defective E-C coupling in jaw muscles, and die shortly after birth. In skeletal muscles, triad junctions are reduced in number. Mutant mice developed less contractile force and abnormal sensitivities to extracellular Ca(2+) were observed. Sarcoplasmic reticulum is often structurally abnormal.|||Sarcoplasmic reticulum membrane|||Specifically expressed in skeletal muscle. Weakly expressed in embryos and neonates. Abundant in young adult muscles.|||The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids. http://togogenome.org/gene/10090:Med20 ^@ http://purl.uniprot.org/uniprot/Q9R0X0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 20 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity). Interacts with PPARG.|||Nucleus http://togogenome.org/gene/10090:Cacng4 ^@ http://purl.uniprot.org/uniprot/A2AAU2|||http://purl.uniprot.org/uniprot/Q9JJV4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Cell membrane|||Interacts with CACNA1C. Identified in a complex with the L-type calcium channel subunits CACNA1C, CACNA2D1 and either CACNB1 or CACNB2 (By similarity). Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Interacts with GRIA1 (By similarity).|||Membrane|||Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs), including GRIA1 and GRIA4. Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization (PubMed:17880894).|||Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs), including GRIA1 and GRIA4. Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. http://togogenome.org/gene/10090:2700062C07Rik ^@ http://purl.uniprot.org/uniprot/Q5XFZ0 ^@ Similarity ^@ Belongs to the UPF0711 family. http://togogenome.org/gene/10090:Brsk1 ^@ http://purl.uniprot.org/uniprot/Q5RJI5 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by phosphorylation on Thr-189 by STK11/LKB1.|||Activity is high in G0, decreases after serum addition, and increases transiently in advanced G1, at G1-S, and in S phases.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cytoplasm|||No visible phenotype. Mice are fertile and healthy. In contrast, mice lacking both Brsk1 and Brsk2 show little spontaneous movement and are only weakly responsive to tactile stimulation: they die within 2 hours of birth. Defects are due to impaired neuronal differentiation and polarity.|||Nucleus|||Phosphorylated at Thr-189 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-189 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-189 by PP2C.|||Present in the gray matter of the brain and spinal cord (at protein level). Expressed in the nervous system, distributed within the brain and spinal cord of embryonic and postnatal animals.|||Presynaptic active zone|||Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-504' and 'Ser-554'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C.|||Synapse|||centrosome|||synaptic vesicle http://togogenome.org/gene/10090:Rpp30 ^@ http://purl.uniprot.org/uniprot/O88796|||http://purl.uniprot.org/uniprot/Q3TF81 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic/archaeal RNase P protein component 3 family.|||Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.|||nucleolus http://togogenome.org/gene/10090:Tmsb15b1 ^@ http://purl.uniprot.org/uniprot/A2AF33 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thymosin beta family.|||Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Olfm5 ^@ http://purl.uniprot.org/uniprot/Q8BU90 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Pde8a ^@ http://purl.uniprot.org/uniprot/O88502 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.|||Expressed in embryos at 7 dpc. Not detected at later stages, including 11, 15 and 17 dpc (PubMed:9671792). In the testis, expression restricted to middle and late pachytene spermatocytes (PubMed:9671792).|||Expressed in multiple tissues, with highest levels in testis, followed by liver, heart, skeletal muscle, and kidney. In the testis, expressed specifically in the seminiferous tubules, in postmitotic pachytene spermatocytes (PubMed:9671792). Low expression, if any, in lung, smooth muscle, pancreas, thyroid, thymus, submaxillary gland, spleen, prostate, epididymus, uterus (PubMed:9671792).|||Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development. Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling. Protects against cell death induced by hydrogen peroxide and staurosporine.|||Inhibited by dipyridimole. Insensitive to selective PDE inhibitor rolipram and to the non-selective inhibitor, IBMX.|||Interacts with RAF1. The interaction promotes RAF1 activity.|||Phosphorylated at Ser-355 by PKA under elevated cAMP conditions, this enhances catalytic activity.|||Reduced phosphorylation of Mapk1/Erk2 and Mapk3/Erk1, both basal levels and those induced by EGF treatment. http://togogenome.org/gene/10090:Natd1 ^@ http://purl.uniprot.org/uniprot/Q9DBW3 ^@ Developmental Stage|||Similarity|||Tissue Specificity ^@ Belongs to the NATD1 family.|||Detected at multiple sites in embryonic day 10.5 embryos, including the genital ridges, the aortic endothelium and endothelium-associated cell clusters within the aortic lumen.|||Expressed in the heart, testis, kidney and lung. http://togogenome.org/gene/10090:Or8u8 ^@ http://purl.uniprot.org/uniprot/Q8VFL0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trip12 ^@ http://purl.uniprot.org/uniprot/G5E870 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UPL family. K-HECT subfamily.|||E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex.|||Embryonic lethality in the middle stage of development. Embryos exhibit growth arrest, while ES cells are viable. ES cells show decreased proliferation, but maintain both the undifferentiated state and the ability to differentiate.|||Interacts with MYC; leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A. Interacts with TRADD; leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A. Interacts with SMARCC1; leading to disrupt interaction with SMARCE1.|||nucleoplasm http://togogenome.org/gene/10090:Or4k15c ^@ http://purl.uniprot.org/uniprot/E9Q8X3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccser2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J2A7|||http://purl.uniprot.org/uniprot/Q3UHI0|||http://purl.uniprot.org/uniprot/S4R211 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CCSER family.|||Expressed in brain (at protein level).|||Microtubule-binding protein which might play a role in microtubule bundling.|||cytoskeleton http://togogenome.org/gene/10090:Brcc3dc ^@ http://purl.uniprot.org/uniprot/Q7M757 ^@ Function|||Similarity ^@ Belongs to the peptidase M67A family. BRCC36 subfamily.|||Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. http://togogenome.org/gene/10090:Nkx2-6 ^@ http://purl.uniprot.org/uniprot/P43688|||http://purl.uniprot.org/uniprot/Q9CVN3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a transcriptional activator (By similarity). In conjunction with NKX2-5, may play a role in both pharyngeal and cardiac embryonic development (PubMed:10733590, PubMed:11390666).|||Belongs to the NK-2 homeobox family.|||Expressed in developing gut endoderm, cardiac progenitors and heart. Expression restricted to the very narrow development period between stages 8.0 and 11.5 dpc. First detected at 8.0 dpc in the endoderm of the lateral walls and lip of the forming foregut pocket, directly juxtaposed to cardiogenic mesoderm. At 8.5 dpc, expressed in the forming pharynx, predominantly in its lateral aspects where pouches will form. From 8.5 to 11.5 dpc, expressed in the ventrolateral endoderm of all forming pouches, as well as in juxtaposed arch ectoderm and mesenchyme. Expression levels decrease as pouches matured. Also expressed in the ventral hindgut endoderm from 9.5 dpc and in a short segment at the foregut-midgut junction spanning the proximal parts of the common bile and pancreatic ducts.|||No visible phenotype; possibly due to the redundancy with NKX2-6. Mutant mice are viable and fertile. No obvious abnormalities in the caudal pharyngeal pouch derivatives (thymus, parathyroid glands, and thyroid gland), heart and gut. In NKX2-5 and NKX2-6 double mutants, the pharynx does not form properly and the development of the atrium is less advanced.|||Not detected in any neonate or adult tissues.|||Nucleus http://togogenome.org/gene/10090:Or52h1 ^@ http://purl.uniprot.org/uniprot/Q8VG19 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Car7 ^@ http://purl.uniprot.org/uniprot/G3XA26|||http://purl.uniprot.org/uniprot/Q3UND9|||http://purl.uniprot.org/uniprot/Q9ERQ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-carbonic anhydrase family.|||Cytoplasm|||Reversible hydration of carbon dioxide. http://togogenome.org/gene/10090:Adam19 ^@ http://purl.uniprot.org/uniprot/O35674|||http://purl.uniprot.org/uniprot/Q3UH67|||http://purl.uniprot.org/uniprot/Q3UHT3 ^@ Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||By calcitriol and during osteoblast differentiation.|||Expressed in the heart and in the tail bud at 8.0 dpc, and then in the cranial and dorsal root ganglia. Also expressed weakly and transiently in the intestine, lung and in bone marrow.|||Interacts with SH3PXD2A.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Participates in the proteolytic processing of beta-type neuregulin isoforms which are involved in neurogenesis and synaptogenesis, suggesting a regulatory role in glial cell. Also cleaves alpha-2 macroglobulin. May be involved in osteoblast differentiation and/or osteoblast activity in bone (By similarity).|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||Widely expressed, with the highest expression in bone, heart and lung, followed by brain and spleen and relatively low expression in liver, skeletal muscle, kidney and testis. In bone, primarily expressed in cell of the osteoblast lineage and not detected in mature osteoclasts. http://togogenome.org/gene/10090:Antxr1 ^@ http://purl.uniprot.org/uniprot/Q9CZ52 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATR family.|||Cell membrane|||Interacts with gelatin and type 1 collagen. Interacts with the actin cytoskeleton.|||Plays a role in cell attachment and migration. Interacts with extracellular matrix proteins and with the actin cytoskeleton. Mediates adhesion of cells to type 1 collagen and gelatin, reorganization of the actin cytoskeleton and promotes cell spreading. Plays a role in the angiogenic response of cultured umbilical vein endothelial cells.|||filopodium membrane|||lamellipodium membrane http://togogenome.org/gene/10090:Arhgap20 ^@ http://purl.uniprot.org/uniprot/Q6IFT4 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Cfap57 ^@ http://purl.uniprot.org/uniprot/Q9D180 ^@ Developmental Stage|||Tissue Specificity ^@ Expression in the palate increases from 12.5 up to 15.5 dpc. At 14.5, detected in the nasal epithelium and detected in the medial edge epithelium. At 15.5 dpc, very strong expression in the nasal respiratory epithelium and epidermis, but not in the oral epithelium. In the nasal epithelium, limited to the respiratory, but not the olfactory, epithelium.|||Predominanly expressed in testis, lung and skin. Weak expression in brain and kidney. http://togogenome.org/gene/10090:Obp2a ^@ http://purl.uniprot.org/uniprot/Q8K1H9 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Expressed in the epididymis from 3 weeks of age.|||Expressed in the liver (at protein level) (PubMed:21908604, PubMed:27827363). Expressed in epididymis (PubMed:15363845).|||Involved in the regulation of systematic glucose homeostasis and insulin sensitivity (PubMed:27827363). Involved in the regulation of liver lipid levels by positive regulation of hepatic lipogenesis and negative regulation of fatty acid beta-oxidation; via downstream transcriptional regulation of CPT1A and hepatic lipogenic program gene expression (PubMed:21908604). May regulate hepatic lipogenesis and fatty acid beta-oxidation in an autocrine or paracrine manner (PubMed:21908604).|||May be involved in the development of hepatic steatosis during obesity.|||Secreted http://togogenome.org/gene/10090:Ppp2r5d ^@ http://purl.uniprot.org/uniprot/Q91V89 ^@ Function|||Similarity ^@ Belongs to the phosphatase 2A regulatory subunit B56 family.|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. http://togogenome.org/gene/10090:Adam11 ^@ http://purl.uniprot.org/uniprot/Q3TZE2|||http://purl.uniprot.org/uniprot/Q7TQG7|||http://purl.uniprot.org/uniprot/Q9R1V4 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A conserved motif [AVN[ED]CD] within the disintegrin-like domain could be involved in the binding to the integrin receptor.|||Abundantly expressed in cerebellar cortex basket cell terminals and pinceaux, weakly expressed in Purkinje cells (at protein level) (PubMed:26269648). Weakly expressed in the heart (PubMed:10433968). Abundantly in expressed in neurons throughout the central nervous system including the telencephalon, diencephalic and brainstem nuclei, cerebellum and spinal cord (PubMed:12088751, PubMed:10433968). Expressed in the peripheral nervous system trigeminal and dorsal root ganglia (PubMed:12088751). Expressed in the ganglion and bipolar cells of the retinae and weakly in the cornea of the eyes (PubMed:12088751). Expressed in the hepatocytes of the parenchyma and hepatic lobules of the liver (PubMed:12088751, PubMed:10433968). Expressed in distinct focal areas in the juxtamedullary cortex of the kidney (PubMed:12088751). Expressed in spermatocytes in the seminiferous tubules of the testes (PubMed:12088751, PubMed:10433968). Expressed in the stratum spinosum of the stratified squamous epithelia of the tongue and esophagus (PubMed:12088751).|||Abundantly expressed in the neural crest-derived structures with low expression in the neural tube at 10 dpc (PubMed:12088751). Expressed in the dorsal root ganglia from 10 to 17 dpc (PubMed:12088751). Expression in the neural tube increases from 11 dpc to 13dpc, at 13 dpc expression is particularly abundant in the diencephalon, brainstem and spinal cord (PubMed:12088751). Expression increases from 13 dpc to postnatal day 1.5 (P1.5) in the telencephalon, whereas expression in the diencephalic and brainstem decreases over this period (PubMed:12088751). Expressed weakly in the developing heart at 13dpc but not at later developmental stages (PubMed:12088751). Expressed weaky in the kidney from 13dpc through to adulthood (PubMed:12088751). Initially expressed in the retinae at 15 dpc, expression is maintained through to adulthood (PubMed:12088751). Abundantly expressed in brown fat beginning at 17 dpc, expression levels are reduced to a low level at P1.5 (PubMed:12088751).|||Interacts with LGI1 and LGI4 (PubMed:18974846). Interacts with KCNA1/KV1.1, KCNA2/KV1.2, DLG4/PSD-95 and ADAM22 (PubMed:26269648).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Morphologically normal, including normal hippocampus and cerebellum morphology (PubMed:16504143). Develop a stress response that includes stationary stance progressing to a high amplitude coarse truncal tremor and ataxic gait when exposed to cold-water swim (PubMed:26269648). Loss of KCNA1/KV1.1 and KCNA2/KV1.2 at cerebellar cortex basket cell distal terminals results in loss of ephaptic inhibitory synchronization of Purkinje cell firing (PubMed:26269648). Impaired spatial learning and motor coordination (PubMed:16504143). Decrease in pain response to chemical stimuli such as subcutaneous injection of formalin or acetic acid (PubMed:16729981).|||Perikaryon|||Presynaptic cell membrane|||Probable ligand for integrin in the brain. This is a non catalytic metalloprotease-like protein. Required for localization of the potassium channel subunit proteins KCNA1/KV1.1 and KCNA2/KV1.2 at cerebellar cortex basket cell distal terminals, is thereby involved in ephaptic inhibitory synchronization of Purkinje cell firing and response to stress (PubMed:26269648). Plays a role in spatial learning and motor coordination (PubMed:16504143). Involved in the nociceptive pain response to chemical-derived stimulation (PubMed:16729981).|||The precursor is cleaved by a furin endopeptidase.|||axon http://togogenome.org/gene/10090:Tgfbr3l ^@ http://purl.uniprot.org/uniprot/D3YZZ2 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in gonadotrope cells, acts as an inhibin B coreceptor and regulates follicle-stimulating hormone (FSH) levels and female fertility.|||Expressed in pituitary gland gonadotrope cells.|||Females show no effects on puberty onset, estrous cyclicity and body weight. They have increased litter sizes relative to wild-type with normal litter frequency. Females ovulate more eggs in natural cycles with increased uterine implantation sites. They have increased numbers of antral follicles and corpora lutea (PubMed:34910520). Double knockout females for TGFBR3L and gonadotrope-specific TGFBR3 are infertile. They have increased serum follicle-stimulating hormone (FSH), pituitary protein content relative to controls. They have larger ovaries with increased numbers of antral follicles and corpora lutea (PubMed:34910520).|||Glycosylated. http://togogenome.org/gene/10090:Scai ^@ http://purl.uniprot.org/uniprot/Q8C8N2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCAI family.|||Cytoplasm|||Expressed in most tissues tested with higher expression levels in brain, spleen and thymus.|||Interacts with DIAPH1. Forms a nuclear ternary complex with MRTFA and SRF.|||Membrane|||Nucleus|||Tumor suppressor which functions to suppress MRTFA-induced SRF transcriptional activity. May function in the RHOA-DIAPH1 signal transduction pathway and regulate cell migration through transcriptional regulation of ITGB1. http://togogenome.org/gene/10090:Wbp1 ^@ http://purl.uniprot.org/uniprot/P97764 ^@ Domain|||Subunit ^@ Binds to the WW domain of YAP1, WWP1 and WWP2. Interacts with WWOX (By similarity). Interacts with NEDD4.|||The PPxY motif 2 mediates interaction with WWOX (By similarity). Both PPxY motifs mediate interaction with NEDD4. http://togogenome.org/gene/10090:Rab44 ^@ http://purl.uniprot.org/uniprot/Q8CB87 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane http://togogenome.org/gene/10090:Mrpl24 ^@ http://purl.uniprot.org/uniprot/Q9CQ06 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL24 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Mindy2 ^@ http://purl.uniprot.org/uniprot/Q6PDI6 ^@ Function|||Sequence Caution|||Similarity ^@ Belongs to the MINDY deubiquitinase family. FAM63 subfamily.|||Contaminating sequence. Potential poly-A sequence.|||Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins. Can also bind to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33' and 'Lys-63'. May play a regulatory role at the level of protein turnover. http://togogenome.org/gene/10090:Smc1b ^@ http://purl.uniprot.org/uniprot/A1L2Z0|||http://purl.uniprot.org/uniprot/Q920F6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMC family. SMC1 subfamily.|||Chromosome|||Forms a heterodimer with SMC3. Component of a meiosis-specific cohesin complex, probably composed of the SMC1B and SMC3 heterodimer attached via their SMC hinge domain, RAD21 (or its meiosis-specific related protein REC8), which link them, and STAG3, which interacts with RAD21 or REC8. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (By similarity).|||Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation and the organization of chromatin loops along the AE. Plays a key role in synapsis, recombination and chromosome movements. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I.|||Nucleus|||Spermatocytes (at protein level). Testis and ovary specific. Not expressed in somatic cells.|||The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC3, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 or REC8 protein, forming a ring structure (By similarity).|||centromere http://togogenome.org/gene/10090:Heatr3 ^@ http://purl.uniprot.org/uniprot/Q8BQM4 ^@ Function ^@ Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5). Required for proper erythrocyte maturation. http://togogenome.org/gene/10090:Vmn2r10 ^@ http://purl.uniprot.org/uniprot/K7N621 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rad52 ^@ http://purl.uniprot.org/uniprot/G5E879|||http://purl.uniprot.org/uniprot/P43352|||http://purl.uniprot.org/uniprot/Q8VEE2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAD52 family.|||Involved in double-stranded break repair. Plays a central role in genetic recombination and DNA repair by promoting the annealing of complementary single-stranded DNA and by stimulation of the RAD51 recombinase.|||Nucleus|||Phosphorylated upon DNA damage by ABL1, and probably by ATM or ATR.|||The full-length protein forms heptameric rings. Interacts with ABL1. Interacts with RPA2; the interaction is direct and associates RAD52 with the RPA complex. Interacts with RAD51AP1. http://togogenome.org/gene/10090:Polr2g ^@ http://purl.uniprot.org/uniprot/P62488 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.|||Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB7 is part of a subcomplex with RPB4 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RPB4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA. Binds RNA (By similarity).|||Nucleus http://togogenome.org/gene/10090:Alkbh1 ^@ http://purl.uniprot.org/uniprot/P0CB42 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Fe(2+) ion per subunit.|||Deficiency results in 80% reduction of the litter size due to embryonic lethality (PubMed:21072209, PubMed:23825659). Surviving pups exhibit a gender bias in favor of males (70% males and 30% females) (PubMed:21072209, PubMed:23825659). Intrauterine growth retardation and placental defects. Altered expression of trophoblast lineage-specific genes (PubMed:18163532). Increased N(6)-methyladenosine (m6A) DNA (PubMed:27027282). No effect on H2AK118 or H2AK119 methylation, suggesting that Alkbh1 does not act as a histone demethylase in vivo (PubMed:27027282). Cells show an strong increase of N(1)-methyladenine-containing tRNAs (PubMed:27745969).|||Dioxygenase that acts as on nucleic acids, such as DNA and tRNA (PubMed:27027282, PubMed:27745969). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:27027282). A number of activities have been described for this dioxygenase, but recent results suggest that it mainly acts as on tRNAs and mediates their demethylation or oxidation depending on the context and subcellular compartment (By similarity). Mainly acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs, with a preference for N(1)-methyladenine at position 58 (m1A58) present on a stem loop structure of tRNAs (PubMed:27745969). Acts as a regulator of translation initiation and elongation in response to glucose deprivation: regulates both translation initiation, by mediating demethylation of tRNA(Met), and translation elongation, N(1)-methyladenine-containing tRNAs being preferentially recruited to polysomes to promote translation elongation (By similarity). In mitochondrion, specifically interacts with mt-tRNA(Met) and mediates oxidation of mt-tRNA(Met) methylated at cytosine(34) to form 5-formylcytosine (f(5)c) at this position (By similarity). mt-tRNA(Met) containing the f(5)c modification at the wobble position enables recognition of the AUA codon in addition to the AUG codon, expanding codon recognition in mitochondrial translation (By similarity). Specifically demethylates DNA methylated on the 6th position of adenine (N(6)-methyladenosine) DNA (PubMed:27027282). N(6)-methyladenosine (m6A) DNA is present at some L1 elements in embryonic stem cells and probably promotes their silencing (PubMed:27027282). Demethylates mRNAs containing N(3)-methylcytidine modification (By similarity). Also able to repair alkylated single-stranded DNA by oxidative demethylation, but with low activity (By similarity). Also has DNA lyase activity and introduces double-stranded breaks at abasic sites: cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites (By similarity). DNA lyase activity does not require alpha-ketboglutarate and iron and leads to the formation of an irreversible covalent protein-DNA adduct with the 5' DNA product (By similarity). DNA lyase activity is not required during base excision repair and class switch recombination of the immunoglobulin heavy chain during B lymphocyte activation (PubMed:23825659). May play a role in placental trophoblast lineage differentiation (PubMed:18163532).|||H2A histone demethylase activity was observed in vitro (PubMed:22961808). The relevance of such activity is however unclear and additional experimental evidence would be needed to confirm this activity in vivo.|||In adult organs, highly expressed in testis, eye, brain and kidney.|||Monomer (By similarity). Interacts with DNAJB6 (PubMed:18163532).|||Nucleus|||The DNA N6-methyl adenine demethylase activity is subject to discussion. While DNA N6-methyl adenine demethylase activity was observed by a report (PubMed:27027282). Another group was unable to detect clear DNA N6-methyl adenine demethylase activity in vivo (PubMed:27745969).|||Weak expression throughout the embryo at 8.5 dpc. As the cells migrate and differentiate during organogenesis, expressed in the spinal cord, forebrain and branchial arches at 9.5 dpc, and also in limb buds at 10.5 dpc. Peak expression at 11.5 dpc in the frontonasal process including telencephalon, maxillary, mandibular and hyoid arches, upper and lower limb buds and midbrain and rhombomere 1 roof plates. Expression decreases considerably from 11.5 dpc to 12.5 dpc (PubMed:21072209). At 8.5 dpc is highly expressed in the chorion and the ectoplacental cone. At 10.5 dpc is highly expressed in multiple trophoblast lineages (spongiotrophoblasts, giant cell trophoblasts, glycogen cells, and labyrinthine trophoblasts). The highest placental level is at 9.5 dpc and subsequently decreases until parturition (PubMed:18163532). http://togogenome.org/gene/10090:Psg22 ^@ http://purl.uniprot.org/uniprot/Q810J1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. CEA family.|||Expressed in placental trophoblast giant cells from 5.5 dpc onwards, with increased expression by 10.5 dpc (at protein level). Also detected on the decidua basalis at 10.5 dpc (at protein level).|||May have an angiogenic function during early placental development. Binds to cell-surface heparan sulfate proteoglycans (HSPGs), and stimulates secretion of the proangiogenic factors VEGFA and TGFB from uterine dendritic cells and natural killer cells. Also induces endothelial tube formation in vitro.|||Secreted http://togogenome.org/gene/10090:Cd79a ^@ http://purl.uniprot.org/uniprot/P11911 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine methylation in the ITAM domain may interfere with the binding of SYK. It promotes signals leading to B-cell differentiation.|||B-cells.|||Cell membrane|||Heterodimer of alpha and beta chains; disulfide-linked. Part of the B-cell antigen receptor complex where the alpha/beta chain heterodimer is non-covalently associated with an antigen-specific membrane-bound surface immunoglobulin of two heavy chains and two light chains. Interacts through its phosphorylated ITAM domain with the SH2 domains of SYK which stimulates SYK autophosphorylation and activation. Also interacts, when phosphorylated on Tyr-204, with the SH2 domain of BLNK/SLP65, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK which is necessary for trafficking of the BCR to late endosomes. Interacts with Src-family tyrosine kinases including FYN and LYN, increasing their activity.|||Mice display impaired B-cell development which does not progress pass the progenitor stage.|||Phosphorylated on tyrosine, serine and threonine residues upon B-cell activation. Phosphorylation of tyrosine residues by Src-family kinases, including LYN, is an early and essential feature of the BCR signaling cascade. The phosphorylated tyrosines serve as docking sites for SH2-domain containing kinases, leading to their activation which in turn leads to phosphorylation of downstream targets. Phosphorylation of serine and threonine residues may prevent subsequent tyrosine phosphorylation.|||Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Also required for BCR surface expression and for efficient differentiation of pro- and pre-B-cells. Stimulates SYK autophosphorylation and activation. Binds to BLNK, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK. Also interacts with and increases activity of some Src-family tyrosine kinases. Represses BCR signaling during development of immature B-cells. http://togogenome.org/gene/10090:Ubl3 ^@ http://purl.uniprot.org/uniprot/Q9Z2M6 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Topaz1 ^@ http://purl.uniprot.org/uniprot/E5FYH1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Important for normal spermatogenesis and male fertility. Specifically required for progression to the post-meiotic stages of spermatocyte development. Seems to be necessary for normal expression levels of a number of testis-expressed gene transcripts, although its role in this process is unclear.|||In both developing female and male gonads, first detected at 12.5 dpc, expression increases until 16.5 dpc and then drops (PubMed:22069478). Divergence between male and female expression starts around 5 days after birth (PubMed:22069478). In ovaries, expression decreases and becomes hardly detectable in adult ovaries, while in testis, expression increases 5 days after birth and becomes strong in the adult (PubMed:22069478). In both males and females, expression is restricted to germ cells (PubMed:22069478). In developing male germ cells, highly expressed at the spermatocyte stage; has little or no expression in round spermatids, elongated spermatids or spermatozoa (PubMed:26358182).|||Males are infertile, while female fertility is not affected. Testis size is significantly reduced with the phenotype apparent from postnatal day 28 (P28) onwards. Testicular histology appears to be normal before P28, but then cell aggregates begin to accumulate in the center of seminiferous tubules. Sperm development arrests at the post-meiotic round spermatid stage, associated with increased apoptosis. Adult testes completely lack round spermatids and spermatozoa. Meiosis appears to be normal up to the pachytene stage, with no apparent effect on synaptonemal complex formation or meiotic sex chromosome inactivation. However, chromosome alignment on the metaphase plate may be abnormal. In stage P20 testes, 99 gene transcripts show abnormal expression levels, including around 10 lincRNAs.|||Restricted to testis, where it localizes to germ cells.|||cytosol http://togogenome.org/gene/10090:Myo1d ^@ http://purl.uniprot.org/uniprot/Q3UG58|||http://purl.uniprot.org/uniprot/Q5SYD0 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Binds a calmodulin chain via each of the two IQ domains. IQ domain 1 mediates interaction with calmodulin both in the presence and in the absence of Ca(2+). IQ domain 2 mediates interaction with calmodulin in the presence of Ca(2+).|||Contrary to the situation in zebrafish, xenopus and drosophila, mammalian MYO1D defects have no effects on left-right body asymmetry.|||Cytoplasm|||Detected in enterocytes at the intestinal brush border membrane. Detected at the tip of intestinal microvilli (at protein level).|||Early endosome|||Interacts (via the two IQ motifs) with calmodulin. Binds an additional calmodulin chain via a third, C-terminal region. Interacts with F-actin.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Perikaryon|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).|||The TH1 domain is required for activity in complementing zebrafish defects in Kupffer's vesicle lumen size.|||Unconventional myosin that functions as actin-based motor protein with ATPase activity (By similarity). Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes (By similarity). Required for normal planar cell polarity in ciliated tracheal cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement in the trachea. Required for normal, polarized cilia organization in brain ependymal epithelial cells (By similarity).|||cell cortex|||dendrite http://togogenome.org/gene/10090:Stk31 ^@ http://purl.uniprot.org/uniprot/Q99MW1 ^@ Caution|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Ser-855 is present instead of the conserved Asp which is expected to be an active site residue.|||Testis specific. Expressed only in male germ cells. http://togogenome.org/gene/10090:Sec24c ^@ http://purl.uniprot.org/uniprot/A0A286YDI8|||http://purl.uniprot.org/uniprot/G3X972|||http://purl.uniprot.org/uniprot/Q80U83 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SEC23/SEC24 family. SEC24 subfamily.|||COPII-coated vesicle membrane|||Endoplasmic reticulum membrane|||Membrane|||cytosol http://togogenome.org/gene/10090:Glg1 ^@ http://purl.uniprot.org/uniprot/Q53WR6|||http://purl.uniprot.org/uniprot/Q61543 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils).|||Cell membrane|||Contains sialic acid residues.|||Fucosylation is essential for binding to E-selectin.|||Golgi apparatus membrane|||Golgi outpost|||Membrane|||Widely expressed; found in myeloid cells, fibroblasts, colon carcinoma, endothelioma, teratocarcinoma, lymphoma, myeloma.|||microtubule organizing center http://togogenome.org/gene/10090:Srcin1 ^@ http://purl.uniprot.org/uniprot/Q9QWI6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of SRC by activating CSK which inhibits SRC activity and downstream signaling, leading to impaired cell spreading and migration. Regulates dendritic spine morphology. Involved in calcium-dependent exocytosis. May play a role in neurotransmitter release or synapse maintenance (By similarity).|||Belongs to the SRCIN1 family.|||Cytoplasm|||Expressed predominantly in central nervous system with high levels detected in cortex, cerebellum, midbrain and spinal cord (at protein level). Also expressed in testis and epithelial-rich tissues such as mammary gland, lung and kidney.|||Interacts with the N-terminal coiled-coil region of SNAP25. Interacts with BCAR1/p130Cas and SRC through its C-terminal domain. Interacts with CSK, CTTN, SORBS3/vinexin, SYP and MAPRE3/EB3 (By similarity).|||Postsynapse|||Postsynaptic density|||Presynapse|||Tyrosine-phosphorylated in response to EGF and to cell adhesion to integrin ligands.|||axon|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Tmem86a ^@ http://purl.uniprot.org/uniprot/Q9D8N3 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adipocyte-specific knockout mice show elevated levels of lysoplasmalogens in adipose tissue and enhanced PKA-signaling pathway and mitochondrial oxidative metabolism in adipose tissue.|||Belongs to the TMEM86 family.|||Catalyzes the hydrolysis of the vinyl ether bond of choline or ethanolamine lysoplasmalogens, forming fatty aldehyde and glycerophosphocholine or glycerophosphoethanolamine, respectively and is specific for the sn-2-deacylated (lyso) form of plasmalogen (PubMed:35835749, PubMed:36592658). Plays an important role in lysoplasmalogen metabolism in the adipocyte tissue and macrophages (PubMed:35835749, PubMed:36592658).|||Endoplasmic reticulum membrane|||Highly expressed in the jejunum, white adipose tissue, kidney and macrophages.|||Sterol-inducible in the macrophages and the induction is mediated by the liver X receptor (LXR) (PubMed:36592658). Up-regulated by high-fat diet in the white adipose tissue (PubMed:35835749). http://togogenome.org/gene/10090:Psenen ^@ http://purl.uniprot.org/uniprot/Q9CQR7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3D-structure analysis of the human homolog indicates that the membrane topology differs from the predictions. Contrary to predictions, the N-terminus contains two short helices that dip into the membrane, but do not cross it. The C-terminus contains the single transmembrane helix. This gives rise to a topology where the N-terminus is cytoplasmic and the C-terminus is lumenal.|||Belongs to the PEN-2 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12522139, PubMed:24941111). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:24941111).|||Golgi stack membrane|||Membrane|||The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PSENEN. http://togogenome.org/gene/10090:Cyth3 ^@ http://purl.uniprot.org/uniprot/O08967 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Autoinhibited by its C-terminal basic region.|||Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate.|||Cell membrane|||Interacts with TAMALIN. Interacts with FRMD4A (PubMed:20080746). Interacts with FRMD4B (PubMed:20080746).|||Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP (PubMed:18042453). Plays a role in the epithelial polarization (PubMed:20080746).|||adherens junction|||cytosol|||tight junction http://togogenome.org/gene/10090:Pitpna ^@ http://purl.uniprot.org/uniprot/P53810 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PtdIns transfer protein family. PI transfer class I subfamily.|||Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidylcholine (PC) between membranes (PubMed:8049244). Shows a preference for PI and PC containing shorter saturated or monosaturated acyl chains at the sn-1 and sn-2 positions (By similarity). Preference order for PC is C16:1 > C16:0 > C18:1 > C18:0 > C20:4 and for PI is C16:1 > C16:0 > C18:1 > C18:0 > C20:4 > C20:3 (By similarity).|||Cytoplasm|||Defects in Pitpna are the cause of the vibrator phenotype which is characterized by early-onset progressive action tremor, degeneration of brain stem and spinal cord neurons, and juvenile death. The mutation is due to the insertion of an intracisternal A particle retrotransposon in intron 4 which results in a 5-fold reduction in protein levels.|||Nucleus|||Phosphorylated by PKC in a calcium and phosphatidylserine-dependent manner. http://togogenome.org/gene/10090:Top2a ^@ http://purl.uniprot.org/uniprot/Q01320 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II topoisomerase family.|||Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+).|||Cytoplasm|||Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.|||Homodimer (By similarity). Interacts with COPS5 (By similarity). Interacts with RECQL5; this stimulates DNA decatenation (By similarity). Interacts with SETMAR; stimulates the topoisomerase activity (By similarity). Interacts with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity (By similarity). Interacts with HNRNPU (via C-terminus); this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA in a RNA-dependent manner (By similarity). Interacts with MCM3AP (By similarity). Interacts with ERCC6 (By similarity). Interacts with PLSCR1 (By similarity). Interacts with GCNA; this interaction allows the resolution of topoisomerase II (TOP2A) DNA-protein cross-links (PubMed:31839538).|||Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (PubMed:1331984). May play a role in regulating the period length of BMAL1 transcriptional oscillation (PubMed:24321095).|||Nucleus|||Phosphorylation has no effect on catalytic activity (By similarity). However, phosphorylation at Ser-1105 by CSNK1D/CK1 promotes DNA cleavable complex formation (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Cspg5 ^@ http://purl.uniprot.org/uniprot/Q71M36 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Altered synaptic transmission at early developmental stages.|||Binds TNR and probably TNC (By similarity). Interacts with ERBB3 and GOPC. Interacts with MDK; this interaction is independent of the presence of chondroitin sulfate chains and promotes elongation of oligodendroglial precursor-like cells (By similarity).|||Cell membrane|||Cell surface|||Different forms of various molecular weight have been observed. Such forms are possibly due to different levels of glycosylation, phosphorylation and/or protein cleavage.|||Endoplasmic reticulum membrane|||Expressed in olfactory bulb, hippocampus, brain stem, spinal cord, cerebrum and cerebellum. Expressed by Purkinje cells in the cerebellum (at protein level). Expressed in immature and mature cerebellum (isoform 1, isoform 2 and isoform 3).|||Golgi apparatus membrane|||Major isoform.|||May function as a growth and differentiation factor involved in neuritogenesis. May induce ERBB3 activation.|||N-glycosylated.|||O-glycosylated; contains chondroitin sulfate glycans. Part-time proteoglycan, expressed in part as a proteoglycan exhibiting chondroitin sulfate glycans and in part as a non-proteoglycan form. The relative amount of both forms depends on tissues and tissue maturation. In the cerebellum the 2 forms coexist while in the cerebrum the proteoglycan form is predominant.|||Phosphorylated; in intracellular and extracellular parts.|||Secreted|||Synaptic cell membrane|||The proteoglycan form decreases from birth to adulthood in the cerebellum concomitant with non-proteoglycan form increase. In the cerebrum the maximum of expression of the proteoglycan is detected 15 days after birth and then decreases gradually to reach half-level at adulthood (at protein level). http://togogenome.org/gene/10090:Zfp46 ^@ http://purl.uniprot.org/uniprot/Q8BPP0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Lens, liver, heart, kidney, spleen and brain.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Thoc6 ^@ http://purl.uniprot.org/uniprot/Q5U4D9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway.Plays a role in apoptosis negative control involved in brain development (By similarity).|||Belongs to the WD repeat THOC6 family.|||Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling.|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Vmn1r257 ^@ http://purl.uniprot.org/uniprot/E9PW18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rab28 ^@ http://purl.uniprot.org/uniprot/Q99KL7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||cilium basal body http://togogenome.org/gene/10090:Cul4b ^@ http://purl.uniprot.org/uniprot/A2A432 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cullin family.|||Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to be formed of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Component of DCX complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either TRPC4AP or DCAF12 as substrate-recognition component. Component of the DCX(AMBRA1) complex with the substrate recognition component AMBRA1. Part of a complex with RBX1 and TIP120A/CAND1. Component of the DCX(WDR77) complex, composed of Cul4b, Ddb1, Wdr77 and Rbx1 (PubMed:35197566). Interacts with RBX1, GRWD1, MLST8, SMU1, TLE2, TLE3, DCAF1, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E (CCNE1 or CCNE2) and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation.|||Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:35197566). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit (PubMed:35197566). CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:35197566). Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage (By similarity). Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication (By similarity). A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (By similarity). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (By similarity). Required for ubiquitination of cyclin E (CCNE1 or CCNE2), and consequently, normal G1 cell cycle progression (By similarity). Component of the DCX(WDR77) complex, which mediates ubiquitination and degradation of Irgm1 in intestinal cells (PubMed:35197566). Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism (By similarity). Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8 (By similarity). With CUL4A, contributes to ribosome biogenesis (By similarity).|||Cytoplasm|||Expressed at high levels in germinal vesicle (GV) stage oocytes and zygotes and at lower levels in MII-stage oocytes and 2-cell stage embryos (PubMed:24357321). Expression decreases from 2-cell stage to blastula (PubMed:24357321).|||Expressed in oocytes (at protein level).|||Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ap2b1 ^@ http://purl.uniprot.org/uniprot/Q5SWR1|||http://purl.uniprot.org/uniprot/Q9DBG3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1) (By similarity). Interacts with EPN1 (By similarity). Interacts with EPS15; clathrin competes with EPS15 (By similarity). Interacts with SNAP91; clathrin competes with SNAP91 (By similarity). Interacts with CLTC; clathrin competes with EPS15, SNAP91 and PIP5K1C (By similarity). Interacts with LDLRAP1 (By similarity). Interacts with AMPH and BIN1 (By similarity). Interacts with ARF6 (GDP-bound) (By similarity). Interacts (dephosphorylated at Tyr-737) with ARRB1; phosphorylation of AP2B1 at Tyr-737 disrupts the interaction (By similarity). Interacts with SLC2A8 (By similarity). Interacts with SCYL1 and SCYL2. Interacts with TGFBR1 and TGFBR2 (By similarity). Interacts with PIP5K1C; clathrin competes with PIP5K1C (By similarity). Interacts with DENND1B (By similarity). Interacts with FCHO1 (By similarity). Interacts with RFTN1 (By similarity). Interacts with KIAA1107 (PubMed:29262337). Together with AP2A1 or AP2A2 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497).|||Belongs to the adaptor complexes large subunit family.|||Cell membrane|||Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly (By similarity).|||Expressed in the brain (at protein level).|||coated pit http://togogenome.org/gene/10090:Rapgef6 ^@ http://purl.uniprot.org/uniprot/B2RUJ6|||http://purl.uniprot.org/uniprot/Q5NCJ0|||http://purl.uniprot.org/uniprot/Q5NCJ1 ^@ Similarity ^@ Belongs to the RAPGEF2 family. http://togogenome.org/gene/10090:Or2aj4 ^@ http://purl.uniprot.org/uniprot/Q7TS53 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tsen34 ^@ http://purl.uniprot.org/uniprot/Q8BMZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tRNA-intron endonuclease family.|||Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events (By similarity).|||Nucleus|||nucleolus|||tRNA splicing endonuclease is a heterotetramer composed of TSEN2, TSEN15, TSEN34/LENG5 and TSEN54. tRNA splicing endonuclease complex also contains proteins of the pre-mRNA 3'-end processing machinery such as CLP1, CPSF1, CPSF4 and CSTF2 (By similarity). http://togogenome.org/gene/10090:Pcdhgb1 ^@ http://purl.uniprot.org/uniprot/Q91XX8 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Jmjd8 ^@ http://purl.uniprot.org/uniprot/Q3TA59 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endoplasmic reticulum lumen|||Functions as a positive regulator of TNF-induced NF-kappaB signaling (By similarity). Regulates angiogenesis and cellular metabolism through interaction with PKM (PubMed:27199445).|||Homozygote knockout Jmjd8 show no obvious phenotype. However, the number of capillaries in muscle tissue is significantly reduced.|||N-glycosylated.|||Oligomer. Dimer. Interacts with PKM; regulates angiogenesis and metabolism.|||Up-regulated upon endothelial differentiation. http://togogenome.org/gene/10090:H2bc9 ^@ http://purl.uniprot.org/uniprot/Q64478 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Krtap19-3 ^@ http://purl.uniprot.org/uniprot/Q925H6 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 19 family.|||Expression in skin and hair follicle is regulated by HOXC13 and by GATA3.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins.|||Strong expression in narrowly defined pattern restricted to the lower and middle cortical regions of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). http://togogenome.org/gene/10090:Trappc2 ^@ http://purl.uniprot.org/uniprot/A2AFP1|||http://purl.uniprot.org/uniprot/Q5J9A9|||http://purl.uniprot.org/uniprot/Q9CQP2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAPP small subunits family. Sedlin subfamily.|||Cytoplasm|||Endoplasmic reticulum-Golgi intermediate compartment|||Expressed in chondrocytes at various stages of differentiation, including proliferating, prehypertrophic and hypertrophic chondrocytes in the distal femoral joint.|||Nucleus|||Part of the multisubunit TRAPP (transport protein particle) complex. Interacts with ENO1, PITX1, SF1 and TRAPPC2L (By similarity). Interacts with TRAPPC3.|||Prevents ENO1-mediated transcriptional repression and antagonizes ENO1-mediated cell death. May play a role in vesicular transport from endoplasmic reticulum to Golgi (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Gm5169 ^@ http://purl.uniprot.org/uniprot/Q5M8P2 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Sema4c ^@ http://purl.uniprot.org/uniprot/Q64151 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell surface receptor for PLXNB2 that plays an important role in cell-cell signaling. PLXNB2 binding promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal brain development, axon guidance and cell migration. Probable signaling receptor which may play a role in myogenic differentiation through activation of the stress-activated MAPK cascade.|||First detected at 14 dpc, levels increase by birth and remain strong in the adult brain (at protein level). Expressed widely in the nervous tissues during development.|||Interacts (via the PDZ-binding motif) with GIPC (via the PDZ domain). Interacts with NCDN. Interacts (via the PDZ-binding motif) with DLG4. Interacts with PLXNB2.|||Partial neonate lethality, due to defects in brain and neural tube development. In about one third of the embryos cranial neural folds fail to converge, leading to an open neural tube and exencephaly. Mice without exencephaly are viable and fertile.|||Postsynaptic density membrane|||Predominantly expressed in brain (at protein level).|||Up-regulated in differentiating myoblasts and upon muscle regeneration (at protein level).|||synaptic vesicle membrane http://togogenome.org/gene/10090:Ndst1 ^@ http://purl.uniprot.org/uniprot/Q3UHN9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. NDST subfamily.|||Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate (PubMed:11087757, PubMed:10758005, PubMed:10664446, PubMed:12590599, PubMed:12692154, PubMed:16020517, PubMed:16056228, PubMed:18337501). Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis (Probable). Plays a role in determining the extent and pattern of sulfation of heparan sulfate (Probable). Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response (PubMed:16056228). Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).|||Golgi apparatus membrane|||Inhibited by long N-sulfated sequences (more than 6 sugar residues) accumulating in its substrates heparan sulfate, and heparin.|||Mice survive until birth but are cyanotic and die neonatally in a condition resembling respiratory distress syndrome. In addition, a minor proportion of mice embryos die during the embryonic period. Mutant mice display cerebral hypoplasia and craniofacial defects, disturbed Ca(2+) kinetics in myotubes. They also display deficiencies L-selectin and chemokine-mediated neutrophil trafficking during inflammatory responses.|||Monomer (By similarity). Interacts with heparan sulfate co-polymerase subunits EXT1 and EXT2.|||The presence of 4 different NDST enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/sulfation reactions, whereas other later on fill in or extend already modified heparan sulfate sequences.|||Widely expressed in adult and throughout development.|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Or10ak7 ^@ http://purl.uniprot.org/uniprot/B1ARV2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp704 ^@ http://purl.uniprot.org/uniprot/Q9ERQ3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation ^@ Expressed from embryonic stage 9.5 dpc to 14.5 dpc. Detected in tissues from all three germ layers, with particularly strong expression in mesodermal derivatives. Strongly expressed in somites and also detected in limb bud mesenchyme, apical epidermal ridge (AER), otic vesicle, and nephrogenic mesenchyme. Expression in somites follows an anterior-to-posterior gradient of activation and localizes to somite myotomes. In limbs, first detected at stage 10.5 dpc, probably in a subset of muscle precursor cells. Expression in developing muscles continues during stage 14.5 dpc. Found in a subset of tendon precursors, particularly in the distal region of the limb. Also detected in ectoderm at the digit tips. Other notable sites of expression at stage 11.5 dpc include skin epithelium in the posterior embryo, thyroid rudiment, ventral neural tube, roof plate, floor plate, dorsal aorta, sympathetic chain ganglia, endolymphatic duct, otic vesicle epithelium and vascular wall.|||No visible phenotype.|||Nucleus|||The CR1 and CR2 motifs mediate sequence-specific DNA binding, and are important for binding to the MYOD1 enhancer.|||Transcription factor which binds to RE2 sequence elements in the MYOD1 enhancer. http://togogenome.org/gene/10090:Atp9a ^@ http://purl.uniprot.org/uniprot/O70228|||http://purl.uniprot.org/uniprot/Q505G9|||http://purl.uniprot.org/uniprot/Q8C288|||http://purl.uniprot.org/uniprot/Q8C4G3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP9A knock down results in muscle weakness, memory impairment and hyperkinetic movement disorders. Abnormal neurite morphology and impaired synaptic transmission are found in the primary motor cortex and hippocampus of knocked-down mice.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Cell membrane|||Early endosome membrane|||Found in most tissues except spleen. Also detected in fetal tissues. Expressed in brain (PubMed:36604604).|||Heterotrimer with MON2 and DOP1B; this complex regulates SNX3-retromer mediated endosomal sorting of WLS. Interacts with RAB5A and RAB11A.|||Late endosome membrane|||Membrane|||Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation (PubMed:36604604). Also involved in endosome to trans-Golgi network retrograde transport (By similarity). In complex with MON2 and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS, a transporter of Wnt morphogens in developing tissues. Participates in the formation of endosomal carriers that direct WLS trafficking back to Golgi, away from lysosomal degradation. Appears to be implicated in intercellular communication by negatively regulating the release of exosomes. The flippase activity towards membrane lipids and its role in membrane asymmetry remains to be proved. Required for the maintenance of neurite morphology and synaptic transmission (PubMed:36604604).|||Recycling endosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Cage1 ^@ http://purl.uniprot.org/uniprot/Q5IR70 ^@ Tissue Specificity ^@ Expressed in spermatids and spermatozoa. Localized to the acrosomal matrix and acrosomal granule. Predominantly expressed during postmeiotic stages of spermatogenesis. http://togogenome.org/gene/10090:Prl3d3 ^@ http://purl.uniprot.org/uniprot/Q8CGZ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Ccdc3 ^@ http://purl.uniprot.org/uniprot/Q9D6Y1 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in aorta and adipose tissue. Enriched in mature adipocytes. Over-expressed in adipose tissue from either hormonally-induced or nutritionally-regulated obese mice models.|||Homodimer.|||Mice exhibit a lean phenotype with reduced fat mass and smaller adipocyte size compared to wild type mice. Adipose tissue exhibit decreased levels of lipogenic genes, such as fatty-acid synthase (FASN), acetyl-CoA carboxylase (ACACA) and diacylglycerol O-acyltransferase-2 (DGAT2). Mice exhibit strongly inhibited age-related hepatic steatosis and decreased number of inflammatory cells in epididymal adipose tissue.|||N-glycosylated.|||Negatively regulates TNF-alpha-induced pro-inflammatory response in endothelial cells (ECs) via inhibition of TNF-alpha-induced NF-kappaB activation in ECs (By similarity). Positively regulates lipid accumulation in adipose cells (PubMed:25605713).|||Secreted http://togogenome.org/gene/10090:Kcna5 ^@ http://purl.uniprot.org/uniprot/Q61762 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.|||Cell membrane|||Highly expressed in heart and moderately in brain. Low levels in thymus, skeletal muscle and spleen. Not expressed in liver, lung or kidney.|||Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1 (By similarity). Interacts with UBE2I (By similarity).|||Inactive. Inhibits expression of isoform 1 and isoform 2.|||No visible phenotype. The action potential in myocytes is not prolonged by low concentrations of 4-aminopyridine, contrary to the situation in wild-type.|||Sumoylated on Lys-212, and Lys-525, preferentially with SUMO3. Sumoylation regulates the voltage sensitivity of the channel (By similarity).|||The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:8226976, PubMed:11349004). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (PubMed:8226976, PubMed:11349004). May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity). http://togogenome.org/gene/10090:Cyp4f37 ^@ http://purl.uniprot.org/uniprot/Q3V1F1 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Stfa2 ^@ http://purl.uniprot.org/uniprot/P35174 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cystatin family.|||Cytoplasm|||This is an intracellular thiol proteinase inhibitor. http://togogenome.org/gene/10090:Pip5k1c ^@ http://purl.uniprot.org/uniprot/O70161 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to some authors, mutants die within hours after birth and are unable to feed after birth (PubMed:15386003). According to another report, mutants are embryonically lethal at organogenesis stage, and display cardiovascular and neuronal defects (PubMed:15386003). PIP5K1C and PIP5K1B double mutant mice die within minutes after birth. PIP5K1C and PIP5K1A double mutant mice are embryonic lethal. Bone marrow-derived macrophages are defective in phagocytosis, attachment to IgG-opsonized particles and Fc-gamma-R clustering, and display highly polymerized actin cytoskeleton. Neurons display defects in synaptic transmission due to defects in synaptic vesicle trafficking at different levels. T-cells mutant for isoform 1 display increase adhesion and polarization.|||Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells (By similarity).|||Activated by phosphatidic acid.|||Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:9535851, PubMed:14741049, PubMed:20622009, PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (By similarity). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Together with PIP5K1A, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (PubMed:19153220). Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport (PubMed:15386003). Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis (By similarity). Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2) (PubMed:16707488). Required for clathrin-coated pits assembly at the synapse (By similarity). Participates in cell junction assembly (By similarity). Modulates adherens junctions formation by facilitating CDH1/cadherin trafficking (By similarity). Required for focal adhesion dynamics (PubMed:12422220). Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions (By similarity). Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins (By similarity). Required for uropodium formation and retraction of the cell rear during directed migration (PubMed:17928408). Has a role in growth factor-stimulated directional cell migration and adhesion (PubMed:17635937). Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor (PubMed:17635937). Negative regulator of T-cell activation and adhesion (PubMed:20855869). Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor (PubMed:20855869). Together with PIP5K1A has a role during embryogenesis and together with PIP5K1B may have a role immediately after birth (PubMed:17609388, PubMed:20622009).|||Cell membrane|||Cytoplasm|||Endomembrane system|||Expression increases during embryonic development and continued to steadily increase postnatally.|||High expression in brain. Also detected in lung, thymus, heart, testicle, kidney and embryo. Highly expressed in forebrain, in particular in cerebellum, hippocampus and cerebral cortex.|||Isoform 1 interacts with TLN1 (PubMed:12422220, PubMed:14691141, PubMed:16707488). Interacts with TLN2; interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity (By similarity). May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6 (By similarity). Interacts with AP2B1 (PubMed:19287005). Isoform 1 interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C (PubMed:16707488). Interacts with CDH1 (By similarity). Interacts with CSK. Interacts with PLCG1; interaction is abolished upon EGF stimulation (PubMed:17635937). Interacts with LAPTM4B; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C (By similarity).|||Phosphorylation on Ser-645 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-644 is necessary for targeting to focal adhesions. Phosphorylation on Ser-645 and Tyr-644 are mutually exclusive. Phosphorylated by SYK and CSK. Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-634 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-644 enhances binding to tailins (TLN1 and TLN2); others that phosphorylation at Tyr-644 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-645.|||adherens junction|||focal adhesion|||phagocytic cup|||ruffle membrane|||uropodium http://togogenome.org/gene/10090:Vmn1r114 ^@ http://purl.uniprot.org/uniprot/L7N226 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rgs6 ^@ http://purl.uniprot.org/uniprot/Q9Z2H2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts with GNB5 (By similarity). Interacts with RGS7BP, leading to regulate the subcellular location of the heterodimer formed with GNB5 (PubMed:15632198, PubMed:15897264). Interacts with GNAI1 (By similarity).|||Membrane|||Nucleus|||Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. The RGS6/GNB5 dimer enhances GNAO1 GTPase activity.|||The RGS domain interacts avidly with Galpha and mediates the acceleration of Galpha-mediated GTP hydrolysis.|||cytosol http://togogenome.org/gene/10090:Pramel38 ^@ http://purl.uniprot.org/uniprot/J3QPH3 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Itpkb ^@ http://purl.uniprot.org/uniprot/B2RXC2 ^@ Similarity ^@ Belongs to the inositol phosphokinase (IPK) family. http://togogenome.org/gene/10090:Cyp4f17 ^@ http://purl.uniprot.org/uniprot/G3UW78 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Thbs1 ^@ http://purl.uniprot.org/uniprot/Q3TR40|||http://purl.uniprot.org/uniprot/Q80YQ1 ^@ Caution|||Similarity ^@ Belongs to the thrombospondin family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Trhr2 ^@ http://purl.uniprot.org/uniprot/Q9ERT2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for thyrotropin-releasing hormone (TRH). Upon ligand binding, this G-protein-coupled receptor triggers activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway. http://togogenome.org/gene/10090:Unc5a ^@ http://purl.uniprot.org/uniprot/Q8K1S4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the unc-5 family.|||Cell membrane|||Homodimer and homooligomer. Interacts with the cytoplasmic part of DCC. Interacts with MAGED1. Interacts with PRKCABP, possibly mediating some interaction with PKC (By similarity). Interacts (via extracellular domain) with FLRT2 (via extracellular domain) (PubMed:25374360). Interacts (via extracellular domain) with FLRT3 (via extracellular domain) (PubMed:22405201).|||Membrane raft|||Phosphorylated on cytoplasmic tyrosine residues (By similarity). Phosphorylated by PKC in vitro (By similarity).|||Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.|||Receptor for netrin required for axon guidance. Functions in the netrin signaling pathway and promotes neurite outgrowth in response to NTN1. Mediates axon repulsion of neuronal growth cones in the developing nervous system in response to netrin. Axon repulsion in growth cones may be mediated by its association with DCC that may trigger signaling for repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand.|||Restricted to central nervous system.|||The ZU5 domain mediates the interaction with MAGED1, which participates in the induction of apoptosis.|||neuron projection http://togogenome.org/gene/10090:Ppp1r3g ^@ http://purl.uniprot.org/uniprot/Q9CW07 ^@ Function|||Induction ^@ Glycogen-targeting subunit for protein phosphatase 1 (PP1). Involved in the regulation of hepatic glycogenesis in a manner coupled to the fasting-feeding cycle and distinct from other glycogen-targeting subunits.|||Up-regulated during fasting and down-regulated after feeding. http://togogenome.org/gene/10090:Dnajb7 ^@ http://purl.uniprot.org/uniprot/Q9QYI8 ^@ Function ^@ Probably acts as a co-chaperone. http://togogenome.org/gene/10090:Cnpy1 ^@ http://purl.uniprot.org/uniprot/Q4VAB4 ^@ Similarity ^@ Belongs to the canopy family. http://togogenome.org/gene/10090:Klk1b21 ^@ http://purl.uniprot.org/uniprot/Q61759 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||By T protein.|||Detectable in testis 4 weeks after birth, becoming more prominent thereafter.|||Expressed in testis and submaxillary gland. In the testis, expression localized specifically to Leydig cells in the interstitial tissues.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. Displays trypsin-like substrate specificity and shows activity towards casein, gelatin, fibronectin and IGFBP3.|||Inhibited by protease inhibitors diisopropylfluorophosphate, leupeptin, antipain, benzamidine, phenylmethylsulfonyl fluoride and soybean trypsin inhibitor. http://togogenome.org/gene/10090:Dus3l ^@ http://purl.uniprot.org/uniprot/A0A0R4IZY9|||http://purl.uniprot.org/uniprot/Q91XI1 ^@ Function|||Similarity ^@ Belongs to the Dus family. Dus3 subfamily.|||Belongs to the dus family. Dus3 subfamily.|||Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Mainly modifies the uridine in position 47 (U47) in the D-loop of most cytoplasmic tRNAs. Also able to mediate the formation of dihydrouridine in some mRNAs, thereby regulating their translation. http://togogenome.org/gene/10090:Trp53 ^@ http://purl.uniprot.org/uniprot/P02340|||http://purl.uniprot.org/uniprot/Q3UGQ1|||http://purl.uniprot.org/uniprot/Q549C9|||http://purl.uniprot.org/uniprot/Q80ZA1 ^@ Caution|||Cofactor|||Disease Annotation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-379 by CREBBP enhances transcriptional activity. Acetylation of Lys-379 by EP300. Deacetylation of Lys-379 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner. Acetylation at Lys-378 increases stability. Deacetylation at Lys-378 by SIRT6 decreases its stability, thereby regulating cell senescence.|||Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression.|||Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By similarity). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By similarity). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression (By similarity). Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis, but seems to have to effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492).|||Belongs to the p53 family.|||Binds 1 zinc ion per subunit.|||Binds DNA as a homotetramer.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain with a peak seen at ZT8.|||Forms homodimers and homotetramers (By similarity). Binds DNA as a homotetramer. Interacts with AXIN1 (PubMed:15526030). Probably part of a complex consisting of TP53, HIPK2 and AXIN1 (PubMed:15526030). Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. Interacts with ING4; this interaction may be indirect (PubMed:12702766). Found in a complex with CABLES1 and TP73 (PubMed:11706030). Interacts with HIPK1, HIPK2, and TP53INP1. Interacts with WWOX. Interacts with USP7 and SYVN1 (PubMed:14719112). Interacts with HSP90AB1. Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity (PubMed:19151705). Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F (PubMed:10644996). Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction. Interacts (via DNA-binding domain) with MAML1 (via N-terminus). Interacts with MKRN1. Interacts with PML (via C-terminus). Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53. Interacts (phosphorylated at Ser-18 by ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates stress-induced TP53-dependent inhibition of cell proliferation. Interacts with PPP2R2A. Interacts with AURKA, DAXX, BRD7 and TRIM24 (PubMed:19556538). Interacts (when monomethylated at Lys-379) with L3MBTL1. Interacts with GRK5. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to DNA damage. Interacts with CDK5 in neurons. Interacts with AURKB, SETD2, UHRF2 and NOC2L. Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2. Interacts with PRKCG. Interacts with PPIF; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by cyclosporin A (CsA). Interacts with SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts with KAT6A. Interacts with UBC9. Interacts with ZNF385B; the interaction is direct. Interacts (via DNA-binding domain) with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest (PubMed:17719541). Interacts with ANKRD2. Interacts with RFFL and RNF34; involved in p53/TP53 ubiquitination. Interacts with MTA1 and COP1. Interacts with CCAR2 (via N-terminus). Interacts with MORC3. Interacts (via C-terminus) with POU4F2 (via C-terminus). Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53. Interacts with AFG1L; mediates mitochondrial translocation of TP53. Interacts with UBD (By similarity). Interacts with TAF6 (By similarity). Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2 (PubMed:24240685). Interacts with NUPR1; interaction is stress-dependent. Forms a complex with EP300 and NUPR1; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity). Interacts with PRMT5 in response to DNA damage; the interaction is TTC5/STRAP dependent (By similarity). Interacts with PPP1R13L (via SH3 domain and ANK repeats); the interaction inhibits pro-apoptotic activity of p53/TP53 (By similarity). Interacts with PPP1R13B/ASPP1 and TP53BP2/ASPP2; the interactions promotes pro-apoptotic activity (By similarity). When phosphorylated at Ser-18, interacts with DDX3X and gamma-tubulin (By similarity). Interacts with KAT7/HBO1; leading to inhibit histone acetyltransferase activity of KAT7/HBO1 (By similarity). Interacts (via N-terminus) with E3 ubiquitin-protein ligase MUL1; the interaction results in ubiquitination of cytoplasmic TP53 at Lys-27 and subsequent proteasomal degradation (By similarity). Interacts with S100A4; this interaction promotes TP53 degradation (By similarity). Interacts with TTC5/STRAP; the interaction may result in increased mitochondrial-dependent apoptosis (By similarity). Interacts with NQO1; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity). Interacts with DAZAP2 at TP53 target gene promoters; the interaction is triggered by DNA damage and leads to modulation of the expression of a subset of TP53 target genes, reducing DNA damage-induced cell death by limiting the expression of cell death-mediating TP53 target genes (By similarity). Interacts (via N-terminus) with ZNF768 (via zinc-finger domains); interaction might be facilitated by TP53 oligomerization state (By similarity). Forms a ternary complex with ALDOB and G6PD; this interaction is direct. ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check. Interacts with MORN3; the interactions mediate post-transcriptional modifications of TP53 by MDM2 and SIRT1 (By similarity).|||It is uncertain whether Met-1 or Met-4 is the initiator.|||Mitochondrion matrix|||Monomethylated at Lys-369 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-367 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-369 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-367. Dimethylated at Lys-370 by EHMT1 and EHMT2. Monomethylated at Lys-379 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-367 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity). Monomethylated at Arg-330 and dimethylated at Arg-332 and Arg-334 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity). Polyubiquitinated by MUL1 at Lys-27 which leads to proteasomal degradation (By similarity).|||Nucleus|||PML body|||Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-12 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-21 by VRK1. Phosphorylated on Ser-23 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-23 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Probably phosphorylated on by CDK7 in a CAK complex in response to DNA damage. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-18 leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes (By similarity). Phosphorylated on Ser-389 following UV but not gamma irradiation. Phosphorylated by HIPK1. Phosphorylation at Ser-18 is required for interaction with DDX3X and gamma-tubulin (By similarity).|||Sumoylated with SUMO1. Sumoylated at Lys-383 by UBC9 (By similarity).|||The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase.|||Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation. Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. Ubiquitinated by MKRN1 at Lys-288 and Lys-289, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by COP1, which leads to proteasomal degradation (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (PubMed:25732823). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (PubMed:24240685).|||centrosome|||p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer. http://togogenome.org/gene/10090:Vmn1r19 ^@ http://purl.uniprot.org/uniprot/Q8R2C7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfand2a ^@ http://purl.uniprot.org/uniprot/Q9JII7 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Or2d4 ^@ http://purl.uniprot.org/uniprot/Q9EP55 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zdhhc8 ^@ http://purl.uniprot.org/uniprot/Q2TGE7|||http://purl.uniprot.org/uniprot/Q5Y5T5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family.|||Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.|||Expressed in brain cortex and hippocampus.|||Golgi apparatus membrane|||Membrane|||Mice have normal brain morphology, but female have strong locomotor deficits in open field, due to a greater fear of new environments.|||Mitochondrion membrane|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes. Through the palmitoylation of ABCA1 regulates the localization of the transporter to the plasma membrane and thereby regulates its function in cholesterol and phospholipid efflux (By similarity). Could also pamitoylate the D(2) dopamine receptor DRD2 and regulate its stability and localization to the plasma membrane (By similarity). Could also play a role in glutamatergic transmission (PubMed:15184899).|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Tmem163 ^@ http://purl.uniprot.org/uniprot/Q8C996 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM163 family.|||Cell membrane|||Early endosome membrane|||Homodimer (By similarity). Interacts with MCOLN1 (PubMed:25130899). Interacts with SLC30A1, SLC30A2, SLC30A3 and SLC30A4 (By similarity).|||Late endosome membrane|||Lysosome membrane|||Widely expressed, with high expression in the brain, cerebellum, heart, lung and spleen (PubMed:31697912). In the brain, mainly expressed in the glutaminergic neuron subpopulations (PubMed:17623043).|||Zinc ion transporter that mediates zinc efflux and plays a crucial role in intracellular zinc homeostasis (By similarity). Binds the divalent cations Zn(2+), Ni(2+), and to a minor extent Cu(2+) (By similarity). Is a functional modulator of P2X purinoceptors, including P2RX1, P2RX3, P2RX4 and P2RX7 (By similarity). Plays a role in central nervous system development and is required for myelination, and survival and proliferation of oligodendrocytes (By similarity).|||synaptic vesicle membrane http://togogenome.org/gene/10090:Cryba1 ^@ http://purl.uniprot.org/uniprot/Q9QXC6 ^@ Similarity ^@ Belongs to the beta/gamma-crystallin family. http://togogenome.org/gene/10090:Ghrh ^@ http://purl.uniprot.org/uniprot/P16043|||http://purl.uniprot.org/uniprot/Q544X5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glucagon family.|||GRF is released by the hypothalamus and acts on the adenohypophyse to stimulate the secretion of growth hormone.|||Secreted http://togogenome.org/gene/10090:Rnasel ^@ http://purl.uniprot.org/uniprot/Q05921 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts (via N-terminus) with TMEV leader protein; this interaction prevents RNASEL activation by its substrate 2'-5' oligoadenylates.|||After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family (By similarity).|||Belongs to the protein kinase superfamily.|||By interferons. Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases (OASs). oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNASEL.|||Cytoplasm|||Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis. Might play a central role in the regulation of mRNA turnover (By similarity). Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length (By similarity).|||Expressed in spleen, thymus, lung, testis, kidney, liver and heart.|||Manganese or magnesium. Required for optimal RNA cleavage rates.|||Mitochondrion|||Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL (By similarity).|||The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain.|||The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization.|||The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity. http://togogenome.org/gene/10090:Or8c10 ^@ http://purl.uniprot.org/uniprot/E9PV37 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptprk ^@ http://purl.uniprot.org/uniprot/P35822 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.|||Developmentally regulated with highest expression found in developing areas or in areas capable of developmental plasticity.|||High levels in liver and kidney. Lower levels in lung, brain and heart. Not seen in spleen and testis.|||Membrane|||Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis. Negative regulator of EGFR signaling pathway. Forms complexes with beta-catenin and gamma-catenin/plakoglobin. Beta-catenin may be a substrate for the catalytic activity of PTPRK/PTP-kappa.|||This protein undergoes proteolytic processing. http://togogenome.org/gene/10090:Tlcd4 ^@ http://purl.uniprot.org/uniprot/Q8CGF5 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TLCD4 family.|||It is uncertain whether Met-1 or Met-14 is the initiator.|||Membrane http://togogenome.org/gene/10090:Alox5 ^@ http://purl.uniprot.org/uniprot/P48999 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||Can be converted from pro-inflammatory 5-lipoxygenase to anti-inflammatory 15-lipoxygenase by reducing the volume of the substrate-binding pocket.|||Catalyzes the oxygenation of arachidonate to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:7629107, PubMed:7809134, PubMed:7969451, PubMed:23246375, PubMed:31642348). Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (By similarity). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:31642348). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma)(PubMed:21307302). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31642348). In addition to inflammatory processes, participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (PubMed:24226420, PubMed:23720274, PubMed:17392829, PubMed:28965882). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21224059). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (PubMed:28694473, PubMed:18421434). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (PubMed:24906289).|||Cytoplasm|||Expressed in skin Langerhans cells and their emigrated counterparts in draining lymph nodes (PubMed:17392829). Highly expressed in circulating leukocytes (PubMed:21307302).|||Homodimer. Interacts with ALOX5AP and LTC4S. Interacts with COTL1, the interaction is required for stability and efficient catalytic activity. Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS). Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1.|||Homozygous mice for ALOX5 are also present in the expected ratios. Mice are indistinguishable in growth and size from wild type littermates (PubMed:7809134). Homozygous mice for ALOX5 show no apparent abnormalities up to ten months of age under normal physiological conditions, except that the spleen is usually smaller for 8-week-old mice (PubMed:7969451).|||IncreaseD by both NF-kappa-B and SP1 in LPS-treated monocytes.|||Nucleus envelope|||Nucleus intermembrane space|||Nucleus matrix|||Nucleus membrane|||Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-524 by PKA has an inhibitory effect. Phosphorylation on Ser-272 prevents export from the nucleus. Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2.|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Tmem134 ^@ http://purl.uniprot.org/uniprot/Q8R0J4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM134/TMEM230 family.|||Membrane|||perinuclear region http://togogenome.org/gene/10090:Gm20861 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Fut7 ^@ http://purl.uniprot.org/uniprot/E2D0W5|||http://purl.uniprot.org/uniprot/Q11131|||http://purl.uniprot.org/uniprot/Q3SWS0 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 10 family.|||Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal alpha2,3 sialylated lactosamine unit of a glycoprotein or a glycolipid-linked sialopolylactosamines chain through an alpha-1,3 glycosidic linkage and participates in the final fucosylation step in the biosynthesis of the sialyl Lewis X (sLe(x)), a carbohydrate involved in cell and matrix adhesion during leukocyte trafficking and fertilization (PubMed:8752218, PubMed:8626519, PubMed:15843584, PubMed:10882744, PubMed:11535629, PubMed:12359718, PubMed:11485743). In vitro, also synthesizes sialyl-dimeric-Lex structures, from VIM-2 structures and both di-fucosylated and trifucosylated structures from mono-fucosylated precursors (By similarity). However does not catalyze alpha 1-3 fucosylation when an internal alpha 1-3 fucosylation is present in polylactosamine chain and the fucosylation rate of the internal GlcNAc residues is reduced once fucose has been added to the distal GlcNAc (By similarity). Also catalyzes the transfer of a fucose from GDP-beta-fucose to the 6-sulfated a(2,3)sialylated substrate to produce 6-sulfo sLex mediating significant L-selectin-dependent cell adhesion (PubMed:8752218, PubMed:10894166). Through sialyl-Lewis(x) biosynthesis, can control SELE- and SELP-mediated cell adhesion with leukocytes and allows leukocytes tethering and rolling along the endothelial tissue thereby enabling the leukocytes to accumulate at a site of inflammation (PubMed:15843584, PubMed:8752218, PubMed:10882744, PubMed:11535629). May enhance embryo implantation through sialyl Lewis X (sLeX)-mediated adhesion of embryo cells to endometrium (By similarity). May affect insulin signaling by up-regulating the phosphorylation and expression of some signaling molecules involved in the insulin-signaling pathway through SLe(x) which is present on the glycans of the INSRR alpha subunit (By similarity).|||Golgi stack membrane|||Highly expressed in lung and bone marrow and to a much lesser extent in spleen, salivary gland and skeletal muscle.|||Inhibited by NaCl. Inhibited by GDP in a concentration dependent manner, with an IC(50) value of 93 uM. Also inhibited by GMP and GTP. Inhibited by N-ethylmaleimide. Activated by poly(ethylene glycol) by enhancing the thermal stability of FUT7. Activated by Mn2+, Ca2+, and Mg2+. Both panosialin A and B inhibit activity with IC(50) values of 4.8 and 5.3 ug/ml, respectively. Inhibited by gallic acid (GA) and (-)-epigallocatechin gallate (EGCG) in a time-dependent and irreversible manner with IC(50) values of 60 and 700 nM, respectively.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Gm6592 ^@ http://purl.uniprot.org/uniprot/A2AHC7 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Cdca2 ^@ http://purl.uniprot.org/uniprot/Q14B71 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with PPP1CC.|||Nucleus|||Phosphorylated by CDK1. May regulate its subcellular location (By similarity).|||Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phopsphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates (By similarity). http://togogenome.org/gene/10090:Gcc2 ^@ http://purl.uniprot.org/uniprot/Q6P0A4|||http://purl.uniprot.org/uniprot/Q8CHG3 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Extended rod-like protein with coiled-coil domains.|||Golgin which probably tethers transport vesicles to the trans-Golgi network (TGN) and regulates vesicular transport between the endosomes and the Golgi. As a RAB9A effector it is involved in recycling of the mannose 6-phosphate receptor from the late endosomes to the TGN. May also play a role in transport between the recycling endosomes and the Golgi. Required for maintenance of the Golgi structure, it is involved in the biogenesis of noncentrosomal, Golgi-associated microtubules through recruitment of CLASP1 and CLASP2 (By similarity).|||Homodimer. Interacts (via GRIP domain) with RAB6A (preferentially in its GTP-bound form). May interact (RAB6A-dependent) with ARL1; might be involved in GCC2 Golgi localization. Interacts (probably via GRIP domain) with RAB9A (preferentially in its GTP-bound form). Interacts with CLASP1 and CLASP2; recruits both proteins to membranes of the TGN. Interacts with STX16 (By similarity).|||Membrane|||Probable cloning artifact. Incorrect C-terminus.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Igfbp1 ^@ http://purl.uniprot.org/uniprot/P47876 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds equally well IGF1 and IGF2.|||IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Promotes cell migration (By similarity).|||Secreted http://togogenome.org/gene/10090:Gkn2 ^@ http://purl.uniprot.org/uniprot/Q9CQS6 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed from 17.5 dpc onwards.|||Golgi apparatus|||Heterodimer with TFF1; disulfide linked (By similarity). Interacts with TFF2.|||Secreted|||Stomach foveolar epithelium and duodenal Brunner's glands. http://togogenome.org/gene/10090:Or10al6 ^@ http://purl.uniprot.org/uniprot/Q7TRJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il31ra ^@ http://purl.uniprot.org/uniprot/Q8K5B1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with OSMR to form the interleukin-31 receptor which activates STAT3 and to a lower extent STAT1 and STAT5. May function in skin immunity (PubMed:15184896). Mediates IL31-induced itch, probably in a manner dependent on cation channels TRPA1 and TRPV1 (PubMed:24373353). Positively regulates numbers and cycling status of immature subsets of myeloid progenitor cells in bone marrow in vivo and enhances myeloid progenitor cell survival in vitro (PubMed:17379091).|||Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Cell membrane|||Expressed in a subset of dorsal root ganglia neurons (PubMed:16926070, PubMed:24373353, PubMed:25381841). Expressed in spinal cord and trigeminal ganglion (at protein level) (PubMed:25381841). Expressed in skin, testis, bone marrow and thymus (PubMed:15184896).|||Heterodimer with OSMR. Interacts with JAK1 and STAT3.|||Mice do not develop dermatitis upon Il31 overexpression (PubMed:15184896). Decreased levels of immature myeloid progenitor cells in bone marrow and spleen but normal numbers of circulating blood cells (PubMed:17379091).|||N-glycosylated.|||Presynaptic cell membrane|||Primarily expressed at postnatal day 10 in the dorsal root ganglia where expression gradually increases as the development proceed.|||Up-regulated in the diseased tissues of a mouse models of allergic asthma and airway hypersensitivity (PubMed:15184896, PubMed:25847241). Up-regulated by IL31 in dorsal root ganglia (PubMed:25381841). Up-regulated by Th2 cytokines IL4 and IL13 in macrophages (PubMed:25847241).|||axon http://togogenome.org/gene/10090:Ncoa2 ^@ http://purl.uniprot.org/uniprot/E9PV80|||http://purl.uniprot.org/uniprot/Q61026|||http://purl.uniprot.org/uniprot/Q8CBM5 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated (PubMed:31851938). Deacetylation at Lys-780 by SIRT6 stimulates its ability to coactivate PPARA (PubMed:31851938).|||Animals show a glycogenopathy resembling to Von Gierke's disease with impaired growth, fasting hypoglycemia, and an increase in concentrations of triglycerides, cholesterol, free fatty acids, ketone bodies, uric acid and lactic acid in the plasma during fating. They also have increased liver glycogen stores and hepatic steatosis.|||Belongs to the SRC/p160 nuclear receptor coactivator family.|||Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.|||Contains four Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant.|||Expressed in a circadian manner in the liver, brown adipose tissue (BAT), white adipose tissue (WAT), heart, skeletal muscle and suprachiasmatic nucleus (SCN) of the brain. Shows a higher expression during the light phase compared with the dark phase.|||Nucleus|||Present in a complex containing NCOA3, IKKA, IKKB, IKBKG and CREBBP (By similarity). Present in a complex containing CARM1 and EP300/P300 (PubMed:11997499, PubMed:10381882). Interacts (via C-terminus) with CREBBP (By similarity). Interacts (via LXXLL 1, 2 and 3 motifs) with RORA (via AF-2 motif) (PubMed:19039140). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif) (PubMed:16148126). Interacts with APEX1 (By similarity). Interacts with BMAL1 (PubMed:24529706). Interacts with CARM1 (PubMed:10381882). Interacts with CASP8AP2 (PubMed:12477726). Interacts with CLOCK (PubMed:24529706). Interacts with DDX5 (By similarity). Interacts with ESR1 (By similarity). Interacts with HIF1A (By similarity). Interacts with NCOA1 (By similarity). Interacts with NR4A1/Nur77 (By similarity). Interacts with NR4A3; potentiates the activity of the NR4A3 (PubMed:12709428). Interacts with NR1H3 (By similarity). Interacts with NR3C1 (By similarity). Interacts with NR3C2 (PubMed:9111344). Interacts with PSMB9 (By similarity). Interacts with RARA (By similarity). Interacts with RXRA (By similarity). Interacts with RWDD3 (By similarity). Interacts with TTLL5/STAMP (By similarity).|||The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding.|||Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140, PubMed:31851938). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC1 expression (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:11997499, PubMed:12507421, PubMed:16148126, PubMed:19039140). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (PubMed:24529706).|||Ubiquitous. http://togogenome.org/gene/10090:Cit ^@ http://purl.uniprot.org/uniprot/D3YU89|||http://purl.uniprot.org/uniprot/D3Z1U0|||http://purl.uniprot.org/uniprot/E9QL53|||http://purl.uniprot.org/uniprot/F6SBR5|||http://purl.uniprot.org/uniprot/P49025 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A major signal was observed in testis and brain, but it was also detected in thymus, spleen, kidney, heart and lung.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm|||Death before reaching adulthood, probably due to lethal epilepsy. Mice display severe defects in the olfactory bulbs, the hippocampus, and the cerebellum. These defects appear to result from impaired cytokinesis followed by the induction of apoptosis in specific neuroblast populations.|||Detected at 10.5 dpc with highest expression in the developing central nervous system. After 16.5 dpc expression decreases and at two weeks after birth is restricted to the proliferating neuronal precursor cells in the external germinal layer of the cerebellum and subventricular migratory stream.|||Interacts with TTC3 (By similarity). Homodimer (Probable). Directly interacts with KIF14 depending on the activation state (stronger interaction with the kinase-dead form).|||Plays a role in cytokinesis. Displays serine/threonine protein kinase activity.|||Plays a role in cytokinesis. Required for KIF14 localization to the central spindle and midbody. Probable RHO/RAC effector that binds to the GTP-bound forms of RHO and RAC1. It probably binds p21 with a tighter specificity in vivo. Displays serine/threonine protein kinase activity. Plays an important role in the regulation of cytokinesis and the development of the central nervous system. Phosphorylates MYL9/MLC2. http://togogenome.org/gene/10090:Vmn1r241 ^@ http://purl.uniprot.org/uniprot/K9J7G2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gabarapl1 ^@ http://purl.uniprot.org/uniprot/Q8R3R8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATG8 family.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum|||Expressed in testis and heart at high levels.|||Golgi apparatus|||Interacts with ATG13, OPRK1, RB1CC1 and ULK1 (By similarity). Interacts with TP53INP1 and TP53INP2 (By similarity). Directly interacts with SQSTM1 (By similarity). Interacts with ATG3, ATG7 and MAP15 (PubMed:16704426). Interacts with TECPR2 (By similarity). Interacts with TBC1D5 (By similarity). Interacts with MAPK15 (By similarity). Interacts with TRIM5 (By similarity). Interacts with MEFV and TRIM21 (By similarity). Interacts with WDFY3 (By similarity). Interacts with the reticulophagy receptor TEX264 (By similarity). Interacts with UBA5 (By similarity). Interacts with KBTBD6 and KBTBD7; the interaction is direct (By similarity). Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3 (PubMed:34338405). Interacts with Irgm1 (By similarity).|||The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, GABARAPL1-I (PubMed:14530254, PubMed:16704426). The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, GABARAPL1-II (By similarity). During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid (By similarity). ATG4 proteins also mediate the delipidation of PE-conjugated forms required for GABARAPL1 recycling when autophagosomes fuse with lysosomes (PubMed:33795848). In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy (By similarity). ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (PubMed:33795848).|||Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover.|||autophagosome|||cytoskeleton http://togogenome.org/gene/10090:Or2ak5 ^@ http://purl.uniprot.org/uniprot/Q5NCD7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Phf14 ^@ http://purl.uniprot.org/uniprot/Q9D4H9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Chromosome|||Cytoplasm|||Death just after birth due to respiratory failure with lungs showing interstitial hyperplasia (PubMed:22730381, PubMed:23688586). Abnormalities are also observed in other organs such as kidney and lung (PubMed:23688586). Mesenchymal fibroblasts exhibit increased proliferation and increased PDGFRA expression (PubMed:22730381). Conditional knockout in germinal center (GC) B cells results in reduced GC response in the spleen following immune challenge, with fewer and smaller GCs observed (PubMed:33035772).|||Expressed throughout embryogenesis and in the adult.|||High levels detected in testis, lung and spleen and low levels in muscle, heart, intestine and kidney (at protein level) (PubMed:23688586). Widely expressed in adult with increased levels in intestine, colon and lung (PubMed:22730381).|||Histone-binding protein (By similarity). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (PubMed:22730381). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (PubMed:33035772).|||Nucleus|||The N-terminal region, including the PHD-type 1 and 2 zinc fingers and the C2HC pre-PHD-type zinc finger, is required for binding to histone H3. http://togogenome.org/gene/10090:Bmp4 ^@ http://purl.uniprot.org/uniprot/P21275|||http://purl.uniprot.org/uniprot/Q3ULR1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Expressed in the lower molar mesenchyme at 13.5 dpc and 14.5 dpc (PubMed:8898217). Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (at protein level) (PubMed:29148101).|||Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis (PubMed:14973287, PubMed:15206957, PubMed:10049358). Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (PubMed:17301089). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Positively regulates the expression of odontogenic development regulator MSX1 via inducing the IPO7-mediated import of SMAD1 to the nucleus (PubMed:34995814). Required for MSX1-mediated mesenchymal molar tooth bud development beyond the bud stage, via promoting Wnt signaling (PubMed:8898217, PubMed:27713059). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (PubMed:29148101). Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (PubMed:8898217). Can also signal through non-canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt or SRC cascades. For example, induces SRC phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response (By similarity).|||Homodimer; disulfide-linked (By similarity). Interacts with SOSTDC1, GREM2, RGMA, RGMB and RGMC. Part of a complex consisting of TWSG1 and CHRD. Interacts with the serine proteases, HTRA1 and HTRA3; the interaction with either inhibits BMP4-mediated signaling. The HTRA protease activity is required for this inhibition. Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity). Interacts with type I receptor BMPR1A (By similarity). Interacts with type II receptor BMPR2 (By similarity). Interacts with FSTL1; this interaction inhibits the activation of the BMP4/Smad1/5/8 signaling pathway (By similarity). Interacts with SCUBE3 (By similarity).|||Homozygous null embryos contain no primordial germ cells (PubMed:10049358). They also lack an allantois, an extraembryonic mesodermal tissue derived from precursors in the proximal epiblast (PubMed:10049358). Mandibular molar tooth germs arrest in the bud stage (PubMed:27713059). Failure to form the primary enamel knot in the mandibular molar tooth buds at 13.5 dpc. Significantly reduces the expression of Lef1 and Axin2 in the maxillary molar tooth germs and mandibular molar buds at 13.5 dpc (PubMed:27713059). Expression of Dkk2 and Sfrp2 expanded into the distal tooth mesenchyme in molar mandibular tooth buds at 13.5 dpc (PubMed:27713059).|||In the cochlea, detected in nonprosensory regions and outer sulcus (at protein level) (PubMed:32127020). Prior to gastrulation, expressed in the extraembryonic ectoderm. Later, expressed in the extraembryonic mesoderm (PubMed:10049358).|||extracellular matrix http://togogenome.org/gene/10090:Rtl9 ^@ http://purl.uniprot.org/uniprot/Q32KG4 ^@ Miscellaneous ^@ RTL8C is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes. http://togogenome.org/gene/10090:Tns2 ^@ http://purl.uniprot.org/uniprot/Q8CGB6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PTEN phosphatase protein family.|||Cell membrane|||Cytoplasm|||Glomerular defects during postnatal nephrogenesis including severe glomerular basement membrane (GBM) thickening, effacement of podocyte foot processes, and mesangial expansion and sclerosis (PubMed:32390516). Ectopic expression of laminin LAMA2 in the GBM followed by the accumulation of immature laminin components (PubMed:32390516). Decreased adhesion of podocytes to the GBM (PubMed:32390516).|||In the adult kidney, expressed mainly in glomeruli (at protein level) (PubMed:28955049). In the newborn kidney, localizes on the basal surface of podocytes along the glomerular basement membrane and not in endothelial cells (PubMed:32390516). Low expression levels in anabolic skeletal muscles (PubMed:23401856).|||In the newborn kidney, weak expression is first observed in podocytes in the late S-shaped body or early capillary loop stage, increases with glomerular maturation and persists at a high level in mature glomeruli (at protein level) (PubMed:32390516). Expressed in skeletal muscle at 17.5 dpc until post natal day P0 and then decreases at P21 (PubMed:23401856).|||Induced under catabolic conditions in skeletal muscles.|||Interacts with AXL. Interacts with SYK; leading to its phosphorylation. Interacts with SQSTM1 (via PB1 domain); the interaction leads to sequestration of TNS2 in cytoplasmic aggregates with SQSTM1 and promotes TNS2 ubiquitination and proteasomal degradation.|||The SH3 domain mediates binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) (By similarity). It is also required to ensure podocyte integrity while the phosphatase domain is dispensible for podocyte maintenance (PubMed:27246398, PubMed:31723089, PubMed:32390516).|||Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin (By similarity). Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain (By similarity). In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy. Negatively regulates PI3K-AKT pathway activation (By similarity). Dephosphorylates nephrin NPHS1 in podocytes which affects mTORC1 complex activity (By similarity). Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria (By similarity). Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (PubMed:27246398, PubMed:31723089, PubMed:32390516). Enhances RHOA activation in the presence of DLC1 (By similarity). Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix (By similarity).|||Ubiquitinated following sequestration in cytoplasmic aggregates with SQSTM1, leading to proteasomal degradation.|||focal adhesion http://togogenome.org/gene/10090:Vmn2r84 ^@ http://purl.uniprot.org/uniprot/D3YWE3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dph3 ^@ http://purl.uniprot.org/uniprot/D3YXV3|||http://purl.uniprot.org/uniprot/Q8K0W9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DPH3 family.|||Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase (By similarity). Interacts with SERGEF (By similarity).|||Cytoplasm|||Embryonic lethal about 11.5 days after fertilization (PubMed:16648478). Decreases metastasis in a mouse model of melanoma (PubMed:23185508).|||In the embryo, expressed during all stages of development.|||Nucleus|||Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase. Acts as an electron donor to reduce the Fe-S cluster in DPH1-DPH2 keeping the [4Fe-4S] clusters in the active and reduced state. Restores iron to DPH1-DPH2 iron-sulfur clusters which have degraded from [4Fe-4S] to [3Fe-4S] by donating an iron atom to reform [4Fe-4S] clusters, in a manner dependent on the presence of elongation factor 2 and SAM. Associates with the elongator complex and is required for tRNA Wobble base modifications mediated by the elongator complex. The elongator complex is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s 2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine).|||The DPH-type metal-binding (MB) domain can also bind zinc. However, iron is the physiological binding partner as zinc binding impairs the protein electron donor function.|||Widely expressed with highest levels in heart, liver, kidney and testis. http://togogenome.org/gene/10090:Ikbkb ^@ http://purl.uniprot.org/uniprot/A0A0R4J0T4|||http://purl.uniprot.org/uniprot/O88351|||http://purl.uniprot.org/uniprot/Q5D0E0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.|||Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex (By similarity). The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65 (PubMed:20622870). Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1 through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts with TICAM1. Interacts with FAF1; the interaction disrupts the IKK complex formation. Interacts with ATM. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity. Interacts with PDPK1 (By similarity). Interacts with EIF2AK2/PKR (PubMed:10848580). The phosphorylated form interacts with PPM1A and PPM1B. Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-alpha-dependent manner. Interacts with IKBKE. Interacts with ZC3H12A (PubMed:22037600). Interacts with AKAP13 (PubMed:23090968). Interacts with LRRC14; disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core complex formation and leading to a decrease of IKBKB phosphorylation and NF-kappaB activation (By similarity). Interacts with SASH1 (By similarity). Interacts with ARFIP2 (By similarity). Interacts with FKBP5 (By similarity).|||Cytoplasm|||Detected in heart (at protein level) (PubMed:23090968). Expressed in liver, kidney and spleen.|||Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B.|||Membrane raft|||Mice present extensive liver damage from apoptosis and die as embryos. They show a marked reduction in TNF-alpha and IL1-alpha-induced NF-kappa-B activity.|||Nucleus|||Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (By similarity). Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (By similarity). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (By similarity). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (By similarity). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (By similarity). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (By similarity). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (By similarity). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (By similarity). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (By similarity). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (PubMed:30988283). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326420).|||The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG.|||Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. 'Ser-163' may not serve as a monoubiquitination site. Ubiquitination on 'Ser-163' may modulate phosphorylation on C-terminal serine residues.|||Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity. Phosphorylated by MAP3K7/TAK1 in response to NOD1 and NOD2 signaling, promoting activation and phosphorylation of NF-kappa-B inhibitors, leading to NF-kappa-B activation. Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription. Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.|||While it is expressed ubiquitously throughout the mouse embryo, at 9.5 dpc its expression begins to be localized to the brain, neural ganglia, neural tube, and in liver at 12.5 dpc. At 15.5 dpc, the expression is further restricted to specific tissues of the embryo. http://togogenome.org/gene/10090:Tnc ^@ http://purl.uniprot.org/uniprot/Q148T5|||http://purl.uniprot.org/uniprot/Q80YX1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At day 11.5 dpc, expressed in maxillary process. at, 14.5 dpc, also detected in the stomach and at 15.5 dpc expressed in developing bones. During embryogenesis, also expressed in lung, cartilages, liver, brain and peripheral nerves (PubMed:14709716). In kidney, isoform 2 is expressed at birth and isoform 5 at 2 weeks of age. In intestine, isoform 5 is expressed at 13 dpc and isoform 2 at birth. In cerebellum, high levels of isoform 2 at 17 dpc are down-regulated to moderate levels in newborn mice and undetectable levels in adult mice. Similarly, moderate levels of isoform 2 expressed in cerebrum of 17 dpc are gradually down-regulated to undetectable levels in adult mice.|||Belongs to the tenascin family.|||Expressed in kidney, aortic valve, corneal limbus, periosteum around the ribs, cerebellum, stomach and intestine (PubMed:14709716). High levels of isoform 2 in lung and brain of newborn mice. High levels of isoform 5 in thymus, moderate levels in brain of newborn and adult mice. Low level of isoform 2 in adult brain.|||Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth when provided to neurons in culture. May play a role in supporting the growth of epithelial tumors. Ligand for integrins ITGA8:ITGB1, ITGA9:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB6. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (By similarity).|||Homohexamer; disulfide-linked. A homotrimer may be formed in the triple coiled-coil region and may be stabilized by disulfide rings at both ends. Two of such half-hexabrachions may be disulfide linked within the central globule. Interacts with CSPG4 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice show enhanced novelty-induced activity, reduced anxiety, delayed resynchronization to daylight reversal and weaker muscle strength.|||N-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Mtmr2 ^@ http://purl.uniprot.org/uniprot/Q6P572|||http://purl.uniprot.org/uniprot/Q9Z2D1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Early endosome membrane|||Endosome membrane|||Expressed in sciatic nerve and in Schwann cells (at protein level) (PubMed:16399794, PubMed:23297362). Detected in adult dorsal root ganglia, neurons of the central nervous system, motor neurons, cell soma and neurites of sensory neurons, olfactory bulb, cerebellum and hippocampus (PubMed:12045210).|||Homodimer (via coiled-coil domain) (PubMed:14530412, PubMed:16399794). Heterotetramer consisting of one MTMR2 dimer and one SBF2/MTMR13 dimer (PubMed:16399794). Heterodimer with SBF1/MTMR5 (By similarity). Heterodimer with MTMR12 (By similarity).|||In 16.5 dpc embryos, expressed in forebrain, dorsal root ganglia, trigeminal ganglia, kidney, adrenal gland and lung.|||Interaction with SBF1/MTMR5 increases phosphatase activity (By similarity). Increases SBF2/MTMR13 catalytic activity towards phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards phosphatidylinositol 3-phosphate (PubMed:16399794).|||Phosphatase that acts on lipids with a phosphoinositol headgroup (PubMed:12045210, PubMed:16399794). Has phosphatase activity towards pho sphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate (PubMed:12045210, PubMed:16399794). Binds phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate (PubMed:12045210, PubMed:16399794). Stabilizes SBF2/MTMR13 at the membranes (PubMed:23297362). Specifically in peripheral nerves, stabilizes SBF2/MTMR13 protein (PubMed:23297362).|||Phosphorylation at Ser-58 decreases MTMR2 localization to endocytic vesicular structures.|||SBF2/MTMR13 protein levels are decreased in sciatic nerves but not in the brain or in fibroblasts.|||The GRAM domain mediates binding to phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3,4,5-trisphosphate.|||The coiled-coil domain mediates homodimerization (PubMed:14530412). Also mediates interaction with SBF1/MTMR5 and SBF2/MTMR13 (By similarity).|||axon|||perinuclear region http://togogenome.org/gene/10090:Cd2bp2 ^@ http://purl.uniprot.org/uniprot/Q9CWK3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the U5 snRNP complex composed of the U5 snRNA and at least PRPF6, PRPF8, SNRNP200, EFTUD2, SNRNP40, DDX23, TXNL4A and CD2BP2. Interacts directly with TXNL4A and PRPF6. Interacts (via GYF domain) with CD2 (via Pro-rich sequence in the cytoplasmic domain). Interacts with PQBP1 (By similarity).|||Cytoplasm|||Involved in pre-mRNA splicing as component of the U5 snRNP complex that is involved in spliceosome assembly.|||Nucleus http://togogenome.org/gene/10090:Slc25a10 ^@ http://purl.uniprot.org/uniprot/Q9QZD8 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across mitochondrial inner membrane (PubMed:33746082). Plays an important role in gluconeogenesis, fatty acid metabolism, urea synthesis, and sulfur metabolism, particularly in liver, by supplying the substrates for the different metabolic processes (PubMed:33746082, PubMed:16027120, PubMed:30943427). Regulates fatty acid release from adipocytes, and contributes to systemic insulin sensitivity (PubMed:33746082).|||Expressed at very high levels in white adipose tissue (PubMed:10567211, PubMed:33746082). And at low levels in brown adipose tissue, kidney and liver (PubMed:10567211).|||Mitochondrion inner membrane|||Regulated by circadian protein CLOCK (Circadian Locomotor Output Cycles Kaput). http://togogenome.org/gene/10090:Msantd3 ^@ http://purl.uniprot.org/uniprot/Q9CR78 ^@ Similarity ^@ Belongs to the MSANTD3 family. http://togogenome.org/gene/10090:Dynlt2a2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J284|||http://purl.uniprot.org/uniprot/P11985 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein light chain Tctex-type family.|||Could be involved in transmission ratio distortion (trd) in mouse t-haplotype which causes male sterility.|||Cytoplasmic granule|||Expressed in testis (at protein level). Expressed at the pachyten stage of the first meiotic division and in later haploid spermatogenic stages.|||Interacts with CSNK2B.|||May be an accessory component of axonemal dynein and cytoplasmic dynein 1. Candidate for involvement in male sterility.|||Membrane|||cytoskeleton http://togogenome.org/gene/10090:Cacnb1 ^@ http://purl.uniprot.org/uniprot/A2A542|||http://purl.uniprot.org/uniprot/A2A543|||http://purl.uniprot.org/uniprot/A2A545|||http://purl.uniprot.org/uniprot/Q8R3Z5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel beta subunit family.|||Cell membrane|||Detected in the inner nuclear layer in the retina (at protein level) (PubMed:21831364). Detected in skeletal muscle, brain, heart and spleen (PubMed:1385409).|||Membrane|||Regulatory subunit of L-type calcium channels that consist of a pore-forming alpha subunit and auxiliary beta, gamma and delta subunits. Interacts with CACNA1A, CACNA1B, CACNA1C and CACNA1S. Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (By similarity). Interacts with CACNA1S (PubMed:28351836). Identified in a complex with CACNA1C. Identified in a complex with the L-type calcium channel subunits CACNA1C, CACNA2D1, CACNB1 and one of the gamma subunits (CACNG4, CACNG6, CACNG7, or CACNG8) (By similarity). Part of a L-type calcium channel complex that contains CACNA1D, CACNA2D1 and CACNB1. Part of a L-type calcium channel complex that contains CACNA1B, CACNA2D1 and CACNB1 (By similarity). Interacts with JSRP1 (PubMed:16638807). Interacts with RYR1 (PubMed:21320436). Interacts with CBARP (PubMed:24751537).|||Regulatory subunit of L-type calcium channels. Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (By similarity). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane. Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit. Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (By similarity).|||sarcolemma http://togogenome.org/gene/10090:Drg2 ^@ http://purl.uniprot.org/uniprot/Q9QXB9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.|||Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP. When hydroxylated at C-3 of 'Lys-21' by JMJD7, may bind to RNA and play a role in translation.|||Cytoplasm|||Fairly high levels in liver, heart, kidney, and brain. Very low levels in lung, spleen, testis and skeletal muscle.|||Hydroxylated (with S stereochemistry) at C-3 of Lys-21 by JMJD7.|||Interacts with RWDD1; this interaction confers protection to polyubiquitination and proteolytic degradation (PubMed:15676025). Interacts with JMJD7; this interaction is direct (By similarity).|||Nucleus|||Polyubiquitinated. http://togogenome.org/gene/10090:Gp6 ^@ http://purl.uniprot.org/uniprot/P0C191 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated with Fc receptor gamma chain. The GPVI:FcRgamma complex is associated with the Src kinase family FYN and LYN. Interacts with TRAF4 (By similarity). Interacts with COL1A1, but not with COL4A4 (PubMed:24368846).|||Cell membrane|||Collagen receptor involved in collagen-induced platelet adhesion and activation (PubMed:16139873, PubMed:24368846). Plays a key role in platelet procoagulant activity and subsequent thrombin and fibrin formation. This procoagulant function may contribute to arterial and venous thrombus formation. The signaling pathway involves the FcR gamma-chain, the Src kinases (likely FYN or LYN) and SYK, the adapter protein LAT and leads to the activation of PLCG2.|||Expressed at embryonic day 13.5, 14.5 and 16.5. Expression decreases in intensity at day 18.5 and in 1.5 day-old newborn.|||Megakaryocytes and platelets.|||Mice deficient in Gp6 show a complete protection against arterial thrombosis and induced pulmonary thromboembolism, without significant prolongation of bleeding time (PubMed:16139873). Mutant mice deficient in Gp6 and P3h2 are born at the expected Mendelian rate and have no visible phenotype (PubMed:24368846). http://togogenome.org/gene/10090:Fzd7 ^@ http://purl.uniprot.org/uniprot/Q61090|||http://purl.uniprot.org/uniprot/Q810L8 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Endosome membrane|||Interacts with MAGI3 (PubMed:15195140). Interacts with DVL1 (PubMed:15353129). Interacts with CCDC88C/DAPLE; the interaction displaces DVL1 from FZD7, leading to inhibition of canonical Wnt signaling and triggering of non-canonical Wnt responses (By similarity). Interacts with MYOC (By similarity). Binds to SDCBP; this interaction is increased by inositol trisphosphate (IP3) (By similarity). Interacts with glypican GPC3 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Receptor for Wnt proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Activation by WNT8 induces expression of beta-catenin target genes. Following ligand activation, binds to CCDC88C/DAPLE which displaces DVL1 from FZD7 and leads to inhibition of canonical Wnt signaling, activation of G-proteins by CCDC88C and triggering of non-canonical Wnt responses (By similarity). May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Itprip ^@ http://purl.uniprot.org/uniprot/Q3TNL8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ITPRIP family.|||Cell membrane|||Enhances Ca(2+)-mediated inhibition of inositol 1,4,5-triphosphate receptor (ITPR) Ca(2+) release.|||Interacts with ITPR.|||Nucleus outer membrane http://togogenome.org/gene/10090:Nme5 ^@ http://purl.uniprot.org/uniprot/Q3V2L8|||http://purl.uniprot.org/uniprot/Q99MH5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NDK family.|||Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB (PubMed:36417862). Interacts with IQUB (PubMed:36417862).|||Expressed in the trachea, ependymal cells and oviduct (at protein level) (PubMed:32203505). Expressed predominantly in germ cells of the testis. Not expressed in testicular somatic cells.|||First appears in pachytene spermatocytes and increases in abundance in subsequent stages.|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:36417862). Does not seem to have NDK kinase activity. Confers protection from cell death by Bax and alters the cellular levels of several antioxidant enzymes including Gpx5. May play a role in spermiogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species (PubMed:12788088).|||cilium|||flagellum axoneme http://togogenome.org/gene/10090:Pou4f1 ^@ http://purl.uniprot.org/uniprot/P17208 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Able to act as transcription factor, cannot regulate the expression of the same subset of genes than isoform 1 (PubMed:12934100). Does not have antiapoptotic effect on neuronal cells (PubMed:9722627).|||Belongs to the POU transcription factor family. Class-4 subfamily.|||Cytoplasm|||Expressed in mature osteoclasts (at protein level) (PubMed:17668438). Brain, peripheral sensory nervous system and retina (PubMed:8162704). In the adult nervous system, predominates in the medial habenula, superficial gray of the superior colliculus, red nucleus, mesencephalic nucleus of the trigeminal ganglion, nucleus ambiguus, inferior olivary nucleus, and peripheral sensory ganglia (PubMed:8290353).|||Expressed in the spinal cord from 11 dpc to the adult stage (PubMed:8290353). As early as 10.5 dpc to 15.5 dpc, strongly expressed in all dorsal root ganglion neurons (PubMed:22326227). In retinal ganglion cells, expression starts at 15.5 dpc and exhibits a slow decrease with moderate levels detectable at P8 (PubMed:8637595).|||Interacts (via N-terminus) with RIT2; the interaction controls POU4F1 transactivation activity on some neuronal target genes (PubMed:12934100). Isoform 1 interacts with POU4F2 isoform 2; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities (PubMed:8537352). Isoform 1 interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction decreases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (PubMed:9448000).|||Multifunctional transcription factor with different regions mediating its different effects (PubMed:10640682, PubMed:8621561, PubMed:9694219, PubMed:9722627). Acts by binding (via its C-terminal domain) to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes (PubMed:8621561, PubMed:17668438). Regulates the expression of specific genes involved in differentiation and survival within a subset of neuronal lineages. It has been shown that activation of some of these genes requires its N-terminal domain, maybe through a neuronal-specific cofactor (PubMed:12934100). Ativates BCL2 expression and protects neuronal cells from apoptosis (via the N-terminal domain) (PubMed:9722627). Induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins (PubMed:8972215). Exerts its major developmental effects in somatosensory neurons and in brainstem nuclei involved in motor control. Stimulates the binding affinity of the nuclear estrogene receptor ESR1 to DNA estrogen response element (ERE), and hence modulates ESR1-induced transcriptional activity (PubMed:9448000). May positively regulate POU4F2 and POU4F3 (PubMed:8876243). Regulates dorsal root ganglion sensory neuron specification and axonal projection into the spinal cord (PubMed:22326227). Plays a role in TNFSF11-mediated terminal osteoclast differentiation (PubMed:17668438). Negatively regulates its own expression interacting directly with a highly conserved autoregulatory domain surrounding the transcription initiation site (PubMed:12441296).|||Mutants have defective suckling and uncoordinated limb and trunk movements, leading to early postnatal death. They show a loss of neurons in the trigerminal ganglia, the medial habenula, the red nucleus and the caudal region of the inferior olivary nucleus (PubMed:8876243). Mutant dorsal root ganglions are defective in sensory neuron specification, and sensory afferent axons fail to form normal trajectories in the spinal cord (PubMed:22326227).|||Nucleus|||The C-terminal domain is able to act as both DNA-binding domain and a transcriptional activator. The N-terminal domain is also required for transactivation activity on some target genes acting as a discrete activation domain (PubMed:8621561, PubMed:9722627). Neurite outgrowth and expression of genes required for synapse formation are primarily dependent on the C-terminal domain, however the N-terminal domain is required for maximal induction (PubMed:8972215).|||Up-regulated by the osteoclast differentiation factor TNFSF11 (PubMed:17668438). http://togogenome.org/gene/10090:Hint2 ^@ http://purl.uniprot.org/uniprot/Q5M9J2|||http://purl.uniprot.org/uniprot/Q9D0S9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HINT family.|||Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By similarity). Hydrolyzes adenosine 5'-O-p-nitrophenylphosphoramidate (AMP-pNA) (By similarity). May be involved in steroid biosynthesis (By similarity). May play a role in apoptosis (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Csrnp2 ^@ http://purl.uniprot.org/uniprot/Q8BGQ2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AXUD1 family.|||Binds to the consensus sequence 5'-AGAGTG-3' and has transcriptional activator activity. May play a role in apoptosis.|||Highest expression detected in thymus, brain and ovary. Low levels detected in naive T-cells.|||Mice display no obvious defects in development, hematopoiesis or T-cell function. Deletion of Axud1, Csrnp2 and Csrnp3 together causes partial neonatal lethality, suggesting that they have redundant functions.|||Nucleus http://togogenome.org/gene/10090:Rpf2 ^@ http://purl.uniprot.org/uniprot/G3X926|||http://purl.uniprot.org/uniprot/Q9JJ80 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RPF2 family.|||Involved in ribosomal large subunit assembly. May regulate the localization of the 5S RNP/5S ribonucleoprotein particle to the nucleolus.|||nucleolus http://togogenome.org/gene/10090:Baat ^@ http://purl.uniprot.org/uniprot/Q91X34 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the amidation of bile acids (BAs) with the amino acid taurine (PubMed:9215542). Selective for taurine conjugation of cholyl CoA and only taurine-conjugated BAs are found in bile (PubMed:9215542). Amidation of BAs in the liver with taurine prior to their excretion into bile is an important biochemical event in bile acid metabolism (By similarity). This conjugation (or amidation) plays several important biological roles in that it promotes the secretion of BAs and cholesterol into bile and increases the detergent properties of BAs in the intestine, which facilitates lipid and vitamin absorption (By similarity). May also act as an acyl-CoA thioesterase that regulates intracellular levels of free fatty acids (By similarity). In vitro, catalyzes the hydrolysis of long- and very long-chain saturated acyl-CoAs to the free fatty acid and coenzyme A (CoASH), and conjugates glycine to these acyl-CoAs (By similarity).|||Highly expressed in liver, kidney, gallbladder, proximal intestine and distal intestine. Weakly expressed in adrenal gland, lung, brain and muscle.|||Monomer.|||Peroxisome|||cytosol http://togogenome.org/gene/10090:Defa26 ^@ http://purl.uniprot.org/uniprot/Q3L180 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Clec5a ^@ http://purl.uniprot.org/uniprot/Q9R007 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation when its activation leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joints.|||By TNF in bone-marrow derived macrophage colony-stimulating factor-dependent macrophages (PubMed:20212065). Up-regulated during the differentiation of myeloid cell line 32Dcl3 into neutrophils (PubMed:19074552).|||Cell membrane|||Functions as a positive regulator of osteoclastogenesis (PubMed:19251634). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (PubMed:20212065).|||Involved in the pathogenetic mechanisms of Japanese encephalitis virus (JEV) infection of the brain. JEV infection of young mice results in increased expression of CLEC5A in spleen and brain with consequent activation of proinflammatory cytokine secretion.|||Monomer (By similarity). Homodimer (By similarity). The majority of CLEC5A is expressed as a monomeric form on macrophages (By similarity). Interacts with TYROBP/DAP12 (PubMed:10449773). The interaction with TYROBP is required for CLEC5 cell surface expression (PubMed:10449773). Interacts with HCST/DAP10 (PubMed:19074552, PubMed:19251634). Forms a CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP (PubMed:19251634).|||Mutants are viable, are born in the expected Mendelian ratios and have similar numbers of myeloid and lymphoid cell subsets as wild-type animals (PubMed:20212065). Inhibition of autoimmune joint inflammation and preservation of bone density (PubMed:20212065).|||N-glycosylated (PubMed:19074552, PubMed:19251634). Contains sialic acid residues (PubMed:19074552).|||Strong expression in bone marrow cells and thioglycollate-induced neutrophils (at protein level) (PubMed:19074552). Expressed on granulocytes and monocytes from bone marrow and peripheral blood (PubMed:20212065). Expressed in macrophage cell line J-774, but not in T-cell lines, B-cell lines, or mast cell lines (PubMed:10449773). http://togogenome.org/gene/10090:Maff ^@ http://purl.uniprot.org/uniprot/O54791 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. Maf subfamily.|||Detected at 6.5 dpc in the boundary between the extraembryonic and embryonic regions. At 8.5 dpc, weakly expressed in the future gut, allantois, yolk sac endoderm and the ectoplacental cone. At 9.5 dpc, strong expression in the primordial gut and presumptive fetal liver, in the floorplate of the myelencephalon, neural crest cells, spongiotrophoblasts, and giant cells of the placenta. At 12.5 dpc, detected in hepotocytes, in the outflow tract of the heart in a specific subset of dorsal root ganglia, in the cranial nerve ganglia, in the lung primordium, and in the epithelium of the expiratory tract. In newborn, strongly expressed in keratinocytes, in the cartilage, in bronchial epithelia, and bone membrane.|||Highly expressed in the lung, lower expression in the brain, thymus, liver, spleen, intestine, kidney, heart, muscle, and ovary. Not significantly expressed in hematopoietic cells.|||Monomer and homo- or heterodimer. Interacts with MIP. Forms high affinity heterodimers with members of the CNC-bZIP family such as NFE2L1/NRF1.|||Nucleus|||Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves. However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2L1/NRF1, and recruiting them to specific DNA-binding sites. Interacts with the upstream promoter region of the oxytocin receptor gene. May be a transcriptional enhancer in the up-regulation of the oxytocin receptor gene at parturition. http://togogenome.org/gene/10090:Sema4b ^@ http://purl.uniprot.org/uniprot/Q62179 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the semaphorin family.|||Expressed from day 10 in the embryo. Low levels found between days 10-12. Expression peaks on day 13 with moderate levels from then until birth.|||Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons.|||Interacts with GIPC PDZ domain.|||Membrane http://togogenome.org/gene/10090:Ccr1 ^@ http://purl.uniprot.org/uniprot/P51675|||http://purl.uniprot.org/uniprot/Q8BMH9|||http://purl.uniprot.org/uniprot/Q8BVW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in the heart, spleen, lung, peritoneal exudate cells and leukocytes.|||Interacts with CREB3.|||Membrane|||Receptor for a C-C type chemokine. Binds to MIP-1-alpha, RANTES, and less efficiently, to MIP-1-beta or MCP-1 and subsequently transduces a signal by increasing the intracellular calcium ions level. Responsible for affecting stem cell proliferation. http://togogenome.org/gene/10090:Reg1 ^@ http://purl.uniprot.org/uniprot/P43137 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed only in regenerating islets and normal exocrine pancreas, but not in normal pancreatic islets. Expressed strongly in pancreas, moderately in gall bladder, and weakly in liver.|||Might act as an inhibitor of spontaneous calcium carbonate precipitation.|||Secreted http://togogenome.org/gene/10090:Cd79b ^@ http://purl.uniprot.org/uniprot/P15530 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ B-cells.|||Cell membrane|||Heterodimer of alpha and beta chains; disulfide-linked. Part of the B-cell antigen receptor complex where the alpha/beta chain heterodimer is non-covalently associated with an antigen-specific membrane-bound surface immunoglobulin of two heavy chains and two light chains. Interacts with LYN.|||Phosphorylated on tyrosine upon B-cell activation by SRC-type Tyr-kinases such as BLK, LYN and SYK.|||Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation. http://togogenome.org/gene/10090:Ddx56 ^@ http://purl.uniprot.org/uniprot/Q5SVX3|||http://purl.uniprot.org/uniprot/Q9D0R4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX56/DBP9 subfamily.|||May form homooligomeric complexes. Interacts with IRF3 (By similarity). Interacts with OCT4 and POU5F1 (PubMed:32703285).|||Nucleolar RNA helicase that plays a role in various biological processes including innate immunity, ribosome biogenesis or nucleolus organization. Plays an essential role in maintaining nucleolar integrity in planarian stem cells (PubMed:32703285). Maintains embryonic stem cells proliferation by conventional regulation of ribosome assembly and interaction with OCT4 and POU5F1 complex (PubMed:32703285). Regulates antiviral innate immunity by inhibiting the virus-triggered signaling nuclear translocation of IRF3. Mechanistically, acts by disrupting the interaction between IRF3 and importin IPO5. May play a role in later stages of the processing of the pre-ribosomal particles leading to mature 60S ribosomal subunits. Has intrinsic ATPase activity (By similarity).|||RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.|||nucleolus http://togogenome.org/gene/10090:S1pr4 ^@ http://purl.uniprot.org/uniprot/Q9Z0L1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes (By similarity).|||Specifically expressed in fetal and adult lymphoid and hematopoietic tissue. Expressed in lung, spleen, thymus and lymph node but absent in other non-lymphatic tissue. Coexpressed with GNA15 at the same relative levels in all tissues examined, with the highest levels in adult spleen and lung. http://togogenome.org/gene/10090:Or10al4 ^@ http://purl.uniprot.org/uniprot/Q8VFQ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myo1c ^@ http://purl.uniprot.org/uniprot/Q9WTI7 ^@ Caution|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to the myosin tail domain (PH-like) present in its tail domain.|||Cytoplasm|||Cytoplasmic vesicle|||Interacts (via its IQ motifs) with CABP1 and CIB1; the interaction with CABP1 and CIB1 is calcium-dependent (PubMed:17994197). Interacts (via tail domain) with PLEKHB1 (via PH domain); the interaction is not affected by the presence or absence of calcium and CALM (PubMed:15976448). Interacts with POLR1A (PubMed:16514417). Interacts with POLR2A (PubMed:11030652, PubMed:16960872). Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (PubMed:16514417). Interacts (via its IQ motifs) with CALM; this precludes interaction with YWHAB (By similarity). Interacts with YWHAB; this precludes interaction with CALM (By similarity). Interacts with RPS6 (By similarity). Interacts with actin (By similarity). Interacts with LLPH (PubMed:26961175). Interacts with GLUT4 (PubMed:22918957). Interacts (via its IQ motifs) with SH3BGRL3; the interaction is dependent on calcium and takes place at membrane ruffles (By similarity).|||Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation.|||Isoform 2 contains a N-acetylmethionine at position 1.|||Isoform 3 is expressed in small intestine, pancreas, brain, kidney, skin, heart muscle, testis, striated muscle, spleen, liver and lung (at protein level). Expressed in brain, testis, adrenal glands, thymus, spleen, kidney, lung, heart, cochlea and vestibule. Expressed in sensory hair cells of the inner ear. Expressed in adipocytes.|||May be due to a frameshift.|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which then are moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes.|||Nucleus|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).|||Up-regulated by serum.|||cell cortex|||nucleolus|||nucleoplasm|||ruffle membrane|||stereocilium membrane http://togogenome.org/gene/10090:Cacng5 ^@ http://purl.uniprot.org/uniprot/Q544Q4|||http://purl.uniprot.org/uniprot/Q8VHW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Brain. Enriched in Bergman glia, as well as a variety of neuronal populations including locus coeruleus, olfactory bulb, lateral septal nucleus, interpeduncular nucleus, and the CA2 and rostral/medial CA1 regions of hippocampus.|||Membrane|||Postsynaptic density membrane|||Regulates the gating properties of AMPA-selective glutamate receptors (AMPARs). Modulates their gating properties by accelerating their rates of activation, deactivation and desensitization. Displays subunit-specific AMPA receptor regulation. Shows specificity for GRIA1, GRIA4 and the long isoform of GRIA2. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).|||The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma. Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG7 and CACNG8. Interacts with GRIA1, GRIA2, GRIA3 and GRIA4 (By similarity). http://togogenome.org/gene/10090:Or4c126 ^@ http://purl.uniprot.org/uniprot/Q8VFB0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnt2 ^@ http://purl.uniprot.org/uniprot/D3YTU6|||http://purl.uniprot.org/uniprot/D3Z592|||http://purl.uniprot.org/uniprot/D3Z649 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Popdc3 ^@ http://purl.uniprot.org/uniprot/Q9ES81 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the popeye family.|||Expressed in cardiac and skeletal muscle.|||May play a role in the maintenance of heart function mediated, at least in part, through cAMP-binding. May play a role in the regulation of KCNK2-mediated current amplitude (By similarity).|||Membrane http://togogenome.org/gene/10090:Il18rap ^@ http://purl.uniprot.org/uniprot/Q0VBK3|||http://purl.uniprot.org/uniprot/Q9Z2B1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the interleukin-1 receptor family.|||Cell membrane|||Forms a ternary complex with IL18 and IL18R1. Within this complex, IL18R1 is involved in ligand-binding and IL18RAP in signaling leading to NF-kappa-B and JNK activation.|||Impaired IL-18 signaling.|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.|||Within the IL18 receptor complex, does not mediate IL18-binding, but involved in IL18-dependent signal transduction, leading to NF-kappa-B and JNK activation (PubMed:11046021, PubMed:15843532, PubMed:9792649). May play a role in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells (By similarity). http://togogenome.org/gene/10090:Klk1b22 ^@ http://purl.uniprot.org/uniprot/P15948 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Or8c20 ^@ http://purl.uniprot.org/uniprot/L7N1Z5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pi16 ^@ http://purl.uniprot.org/uniprot/Q9ET66 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRISP family.|||Expressed strongly in aorta and skin, and weakly in adipose tissue (at protein level). In heart, found in the extracellular space surrounding cardiomyocytes (at protein level).|||Interacts with PSP94/MSMB.|||May inhibit cardiomyocyte growth.|||N-glycosylated.|||Secreted|||Up-regulated in a mouse model of heart failure. http://togogenome.org/gene/10090:Polr1b ^@ http://purl.uniprot.org/uniprot/P70700 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNA polymerase beta chain family.|||Chromosome|||Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest core component of RNA polymerase I which synthesizes ribosomal RNA precursors. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol I is composed of mobile elements and RPA2 is part of the core element with the central large cleft and probably a clamp element that moves to open and close the cleft.|||nucleolus http://togogenome.org/gene/10090:Or5m5 ^@ http://purl.uniprot.org/uniprot/A0PK66|||http://purl.uniprot.org/uniprot/Q8VFL5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Hpgd ^@ http://purl.uniprot.org/uniprot/Q8VCC1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites (By similarity) (PubMed:8950170). Decreases the levels of the pro-proliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer because of an increase in the expression of cyclooxygenase 2) and generates oxo-fatty acid products that can profoundly influence cell function by abrogating pro-inflammatory cytokine expression. Converts resolvins E1, D1 and D2 to their oxo products, which represents a mode of resolvin inactivation. Resolvin E1 plays important roles during the resolution phase of acute inflammation, while resolvins D1 and D2 have a unique role in obesity-induced adipose inflammation (By similarity).|||Cytoplasm|||Expressed in proximal convoluted tubules of the kidney, where it colocalizes with the prostaglandin transporter SLC22A22 (at protein level) (PubMed:20448048). Expressed in lung, intestine, stomach and liver (PubMed:8950170).|||Homodimer. http://togogenome.org/gene/10090:Klhl8 ^@ http://purl.uniprot.org/uniprot/P59280 ^@ Function|||Subunit ^@ Component of the BCR(KLHL8) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL8 and RBX1. Interacts with RAPSN (By similarity).|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for The BCR(KLHL8) ubiquitin ligase complex mediates ubiquitination and degradation of RAPSN. http://togogenome.org/gene/10090:Spg21 ^@ http://purl.uniprot.org/uniprot/A2RT57|||http://purl.uniprot.org/uniprot/Q9CQC8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily.|||Cytoplasm|||Expressed in cell lines FT.1 and in a L cell fibroblast derivative (at protein level).|||Interacts with CD4. Interacts with ALDH16A1.|||May play a role as a negative regulatory factor in CD4-dependent T-cell activation. http://togogenome.org/gene/10090:Fcgr4 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1G0 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By lipopolysaccharide, interferon beta and IFNG.|||Cell membrane|||Detected on myeloid cells, peripheral blood monocytes, splenic and bone marrow dendritic cells, and thioglycollate-elicited macrophages and neutrophils but absent from lymphoid populations with no expression observed on T cells, B cells, NK cells or other granulocytes (at protein level) (PubMed:16039578, PubMed:19795417). Expressed in peripheral blood leukocytes, spleen, liver, thymus and small intestine (PubMed:12389094, PubMed:17558411). Expressed in splenic dendritic cell subsets (at protein level).|||Forms a heterooligomeric complex with ITAM-containing signaling subunits FCER1G. Interacts (via transmembrane domain) with signaling subunits; this interaction is a prerequisite for receptor complex expression on the cell surface and intracellular signal transduction. Binds the Fc region of antigen-complexed IgG.|||N-glycosylated.|||Phosphorylated following receptor ligation.|||Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG) (PubMed:16039578). Binds with intermediate affinity to both IgG2a and IgG2b (PubMed:16039578, PubMed:17558411, PubMed:19795417). Can bind to IgG2a and IgG2b monomers (PubMed:18949059). Does not display binding to IgG1 or IgG3 (PubMed:16039578). Recognizes neutralizing virus-specific IgGs displayed on the cell surface of infected cells and triggers antibody-dependent cellular cytotoxicity (ADCC). Confers protection to lethal influenza virus infection (PubMed:24412922). On splenic dendritic cells, uptakes antigen immune complexes and efficiently divert them into MHC class I and II antigen presentation pathways to provide for superior priming of CD4-positive and CD8-positive T cell immune responses (PubMed:28389502). Mediates neutrophil activation by IgG complexes redundantly with FCGR2A (PubMed:18097064). Plays a role in promoting bone resorption by enhancing osteoclast differentiation following binding to IgG2a (PubMed:25824719). Also acts as a receptor for the Fc region of immunoglobulin epsilon (IgE) (PubMed:17558411, PubMed:18949059). Binds with low affinity to both the a and b allotypes of IgE (PubMed:18949059). Has also been shown to bind to IgE allotype a only but not to allotype b (PubMed:17558411). Binds aggregated IgE but not the monomeric form and bound monomeric IgG is readily displaced by IgE complexes (PubMed:18949059). Binding to IgE promotes macrophage-mediated phagocytosis, antigen presentation to T cells, production of pro-inflammatory cytokines and the late phase of cutaneous allergic reactions (PubMed:17558411, PubMed:18949059). Mediates enhanced ADCC in response to afucosylated IgGs (PubMed:34485821). http://togogenome.org/gene/10090:Dynlt4 ^@ http://purl.uniprot.org/uniprot/Q8CDY7 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynein light chain Tctex-type family.|||Cytoplasm|||Expression is elevated in spermatocytes, this expression is maintained high in the round spermatids with a decreased in elongated spermatid.|||Interacts with ENG/endoglin, TGFBR2 and TGFBR3. Interacts with PPP1CC.|||Nucleus|||acrosome|||cilium axoneme|||flagellum|||microtubule organizing center http://togogenome.org/gene/10090:Rpl15 ^@ http://purl.uniprot.org/uniprot/Q5M8Q0|||http://purl.uniprot.org/uniprot/Q9CZM2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL15 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit. Interacts with IFIT1 (via TPR repeats 1-4).|||Cytoplasm http://togogenome.org/gene/10090:Gapdh ^@ http://purl.uniprot.org/uniprot/A0A0A0MQF6|||http://purl.uniprot.org/uniprot/D2KHZ9|||http://purl.uniprot.org/uniprot/P16858 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.|||Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues.|||Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:19903941). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:19903941). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (By similarity). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity).|||Homotetramer (PubMed:23071094). Interacts with TPPP; the interaction is direct (By similarity). Interacts (when S-nitrosylated) with SIAH1; leading to nuclear translocation. Interacts with RILPL1/GOSPEL, leading to prevent the interaction between GAPDH and SIAH1 and prevent nuclear translocation. Interacts with CHP1; the interaction increases the binding of CHP1 with microtubules. Associates with microtubules (By similarity). Interacts with EIF1AD, USP25, PRKCI and WARS1. Interacts with phosphorylated RPL13A; inhibited by oxidatively-modified low-densitity lipoprotein (LDL(ox)) (By similarity). Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity (PubMed:23071094). Interacts with TRAF2, promoting TRAF2 ubiquitination (By similarity). Interacts with TRAF3, promoting TRAF3 ubiquitination (By similarity).|||Homotetramer.|||ISGylated.|||Nucleus|||Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation.|||S-nitrosylation of Cys-150 leads to interaction with SIAH1, followed by translocation to the nucleus S-nitrosylation of Cys-245 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity (By similarity).|||Succination of Cys-150 and Cys-245 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits glyceraldehyde-3-phosphate dehydrogenase activity. Fumarate concentration as well as succination of cysteine residues in GAPDH is significantly increased in muscle of diabetic mammals. It was proposed that the S-(2-succinyl)cysteine chemical modification may be a useful biomarker of mitochondrial and oxidative stress in diabetes and that succination of GAPDH and other thiol proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications.|||Sulfhydration at Cys-150 increases catalytic activity.|||The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Coq8a ^@ http://purl.uniprot.org/uniprot/Q60936 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adopts an atypical protein kinase-like fold: while it adopts a core fold similar to that of well-characterized protein kinase-like domains, a number of features are positioned to inhibit the kinase activity: (1) an atypical AAAS motif in an alanine-rich (A-rich) loop that replaces the canonical glycine-rich (G-rich) nucleotide-binding loop and limits ATP binding by establishing an unusual selectivity for ADP and (2) an N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket. Nucleotide-binding opens the substrate binding pocket and flips the active site from inside the hydrophobic core into a catalytically competent, solvent-exposed posture.|||Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:27499294). Its substrate specificity is unclear: does not show any protein kinase activity (PubMed:27499294). Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates (By similarity). Shows an unusual selectivity for binding ADP over ATP (By similarity).|||Autoinhibited by the N-terminal domain, containing the KxGQ motif, that completely occludes the typical substrate binding pocket. Nucleotide-binding relieves inhibition.|||Belongs to the protein kinase superfamily. ADCK protein kinase family.|||Homodimer; homodimerizes via its transmembrane region. Interacts with the multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.|||Membrane|||Mice were born at the expected Mendelian frequency and do not show overt phenotype under normal conditions. They however develop a slowly progressive loss of coordination after birth and develop ataxia and seizures. Defects are due to dysfunctional cerebellar Purkinje cells and defective skeletal muscle. Mice display tissue-specific coenzyme Q deficiency: coenzyme Q levels are normal in younger mice but significantly and specifically reduced in skeletal muscle. However, normal coenzyme Q levels are observed in whole cerebella, suggesting that cerebellar Purkinje cells are specifically affected.|||Mitochondrion|||Present in various tissues (at protein level). http://togogenome.org/gene/10090:Cntnap5c ^@ http://purl.uniprot.org/uniprot/Q0V8T7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neurexin family.|||Expressed from 6 dpc in brain.|||Expressed in brain.|||May play a role in the correct development and proper functioning of the peripheral and central nervous system and be involved in cell adhesion and intercellular communication.|||Membrane http://togogenome.org/gene/10090:Erich6 ^@ http://purl.uniprot.org/uniprot/D3Z6S9 ^@ Similarity ^@ Belongs to the ERICH6 family. http://togogenome.org/gene/10090:Slc66a3 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VLY9|||http://purl.uniprot.org/uniprot/Q3UU83|||http://purl.uniprot.org/uniprot/Q8C6U2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rab3d ^@ http://purl.uniprot.org/uniprot/P35276|||http://purl.uniprot.org/uniprot/Q543Q4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Interacts with RIMS1, RIMS2, RPH3A, RPH3AL and RAB3IP (PubMed:11431472, PubMed:12578829). Interacts with CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (By similarity). Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (PubMed:18849981).|||Phosphorylation of Thr-86 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM and CHML.|||Predominantly expressed in the adipocyte tissue, but is also expressed in several other organs including skin, spleen, heart and lung.|||Protein transport. Probably involved in vesicular traffic (By similarity). May be involved in the insulin-induced exocytosis of glut4-containing vesicles in adipocytes.|||Protein transport. Probably involved in vesicular traffic. http://togogenome.org/gene/10090:Rspo3 ^@ http://purl.uniprot.org/uniprot/Q2TJ95 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis (PubMed:16543246, PubMed:21693646, PubMed:26766444). Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway (PubMed:16543246, PubMed:21693646). Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (PubMed:26766444, PubMed:16543246, PubMed:21693646). Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3 (By similarity).|||Belongs to the R-spondin family.|||Embryonic lethality due to vascular remodeling defects (PubMed:26766444). Conditional knockout in endothelial cells results in impaired developmental and tumor vascular remodeling. Mice show endothelial cell apoptosis and vascular pruning, leading to reduced microvessel density (PubMed:26766444).|||Expressed from day 7.5 in the primitive streak. At day 9.5, it is expressed in various neural and mesodermal derivatives, mainly along dorsal neural tube, diencephalon, somites and tailbud mesoderm. Strongly expressed in limb buds, particularly in the morphogenetically active region such as the apical ectodermal ridge (AER).|||Highly expressed in endothelial cells (PubMed:26766444).|||Interacts with the extracellular domain of FZD8 and LRP6 (PubMed:16543246). It however does not form a ternary complex with FZD8 and LRP6 (PubMed:16543246). Interacts with WNT1 (PubMed:16543246). Binds heparin. Interacts with LGR4, LGR5 and LGR6 (PubMed:21693646).|||Secreted|||The FU repeats are required for activation and stabilization of beta-catenin. http://togogenome.org/gene/10090:Pten ^@ http://purl.uniprot.org/uniprot/A0A6G7SF19|||http://purl.uniprot.org/uniprot/O08586 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. Tumor suppressor, the lipid phosphatase activity is critical for its tumor suppressor function (By similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:10339565, PubMed:19778506, PubMed:31492966). The unphosphorylated form cooperates with MAGI2 to suppress AKT1 activation. In motile cells, suppresses the formation of lateral pseudopods and thereby promotes cell polarization and directed movement. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation (By similarity). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces PTEN phosphorylation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 and results in translocation of the PTEN-DLC1 complex to the posterior of migrating cells to promote RHOA activation (By similarity). Meanwhile, TNS3 switches binding preference from DLC1 to p85 and the TNS3-p85 complex translocates to the leading edge of migrating cells to activate RAC1 activation (By similarity). Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (PubMed:10339565, PubMed:19778506). Involved in the regulation of synaptic function in excitatory hippocampal synapses. Recruited to the postsynaptic membrane upon NMDA receptor activation, is required for the modulation of synaptic activity during plasticity. Enhancement of lipid phosphatase activity is able to drive depression of AMPA receptor-mediated synaptic responses, activity required for NMDA receptor-dependent long-term depression (LTD) (By similarity). May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability (By similarity).|||Belongs to the PTEN phosphatase protein family.|||Constitutively phosphorylated by CK2 under normal conditions. Phosphorylation results in an inhibited activity towards PIP3. Phosphorylation can both inhibit or promote PDZ-binding. Phosphorylation at Tyr-336 by FRK/PTK5 protects this protein from ubiquitin-mediated degradation probably by inhibiting its binding to NEDD4 (By similarity). Phosphorylation by PLK3 promotes its stability and prevents its degradation by the proteasome. Phosphorylation by ROCK1 is essential for its stability and activity. Phosphorylated on Thr-319 and Thr-321 in the C2-type tensin domain following EGF stimulation which changes its binding preference from the p85 regulatory subunit of the PI3K kinase complex to DLC1 (By similarity).|||Cytoplasm|||Expressed in brain (at protein level).|||ISGylated. ISGylation promotes PTEN degradation.|||Monomer. The unphosphorylated form interacts with the second PDZ domain of MAGI2 (By similarity). Interacts with MAGI2, MAGI3, MAST1 and MAST3, but neither with MAST4 nor with DLG5; interaction with MAGI2 increases protein stability (By similarity). Interacts with NEDD4 (By similarity). Interacts with NDFIP1 and NDFIP2; in the presence of NEDD4 or ITCH, this interaction promotes PTEN ubiquitination (By similarity). Interacts (via C2 domain) with FRK (By similarity). Interacts with USP7; the interaction is direct (By similarity). Interacts with ROCK1 (PubMed:20008297). Interacts with XIAP/BIRC4 (PubMed:19473982). Interacts with STK11; the interaction phosphorylates PTEN (By similarity). Interacts with PPP1R16B (By similarity). Interacts with NOP53; regulates PTEN phosphorylation and increases its stability (By similarity). Interacts (via PDZ domain-binding motif) with DLG4; the interaction is induced by NMDA and is required for PTEN location at postsynaptic density (By similarity). Interacts with the regulatory p85 subunit of the PI3K kinase complex and with Rho GTPase-activating protein DLC1; in resting cells, interacts (via C2 tensin-type domain) with p85 but, following growth factor stimulation, PTEN is phosphorylated which leads to weakened interaction with p85 and enhanced interaction (via C2 tensin-type domain) with DLC1 while p85 interaction with TNS3 increases (By similarity).|||Monoubiquitinated; monoubiquitination is increased in presence of retinoic acid. Deubiquitinated by USP7; leading to its nuclear exclusion. Monoubiquitination of one of either Lys-13 and Lys-289 amino acid is sufficient to modulate PTEN compartmentalization (By similarity). Ubiquitinated by XIAP/BIRC4.|||Nucleus|||PML body|||Postsynaptic density|||Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.|||dendritic spine http://togogenome.org/gene/10090:Trex1 ^@ http://purl.uniprot.org/uniprot/Q91XB0 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the exonuclease superfamily. TREX family.|||Binds 2 Mg(2+) per subunit. The second magnesium ion interacts with only one residue. Substitution with Mn(2+) results in partial activity.|||Calcium, lithium and sodium inhibit the exonuclease activity but not the DNA binding.|||Endoplasmic reticulum membrane|||Homodimer (PubMed:17293595, PubMed:17355961, PubMed:22071149). Interacts (via proline-rich region) with TCERG1/CA150 (via the second WW domain) (PubMed:17355961). Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1 (By similarity). Within this complex, directly interacts with SET; this interaction does not result in TREX1 inhibition (By similarity). Also interacts with NME1, but only following translocation to the nucleus (By similarity). Directly interacts with UBQLN1 (via ubiquitin-like domain); the interaction may control TREX1 subcellular location (By similarity).|||Induced by cytosolic DNA. Induced by inflammatory stimuli in a cell-specific fashion. Up-regulated by IFN-alpha and IFN-gamma in B-cells and by LPS and viral and bacterial DNA (via Toll-like receptor signaling) in dendritic cells and macrophages.|||Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:11279105, PubMed:15254239, PubMed:17293595, PubMed:17355961, PubMed:18780819). Prevents cell-intrinsic initiation of autoimmunity (PubMed:18724932, PubMed:24218451). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements (PubMed:18724932). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation (By similarity). Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation (By similarity). Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon (PubMed:18724932). Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates (PubMed:18045533). Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 (By similarity). NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (By similarity).|||Mutant animals exhibit a dramatically reduced survival after weaning, with 50% of survival at 9 weeks (PubMed:18724932) or 17 weeks (PubMed:15254239). In 6-8 week old animals, multiple organs show extensive inflammation. The most severe diffuse lymphocytic infiltration occurs in the heart, followed by the lung, the liver, the smooth muscle of the uterus and the salivary gland with periductal infiltration. Other tissues exhibit only minimal to mild lymphocytic infiltration (PubMed:24218451). The heart phenotype includes inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure. Enlargement of the spleen and lymph nodes is observed in less than 10% of old mice (over 1 year of age) (PubMed:15254239). Mutant animals have a reduced 3'-exonuclease activity. They accumulate ssDNA from endogenous retroelements and produce high levels of autoantibodies. Do not show an increase in spontaneous mutation frequency or cancer incidence. Double knockout of TREX1 and either IRF3, IFNAR1 or RAG2 fully rescues the TREX1 single knockout phenotype (PubMed:18724932).|||Nucleus|||Ubiquitinated, but not targeted to proteasomal degradation. Ubiquitination may be important for interaction with UBQLN1 (By similarity).|||Widely expressed with high expression levels detected in spleen, thymus and uterus.|||cytosol http://togogenome.org/gene/10090:Lrrtm2 ^@ http://purl.uniprot.org/uniprot/Q8BGA3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRTM family.|||Cell membrane|||Expressed in neuronal tissues.|||Interacts with DLG4. Interacts with neurexin NRXN1; interaction is mediated by heparan sulfate glycan modification on neurexin.|||Involved in the development and maintenance of excitatory synapses in the vertebrate nervous system. Regulates surface expression of AMPA receptors and instructs the development of functional glutamate release sites. Acts as a ligand for the presynaptic receptors NRXN1-A and NRXN1-B (By similarity).|||Postsynaptic cell membrane|||Synaptogenic effects are mediated by the extracellular LRR region. http://togogenome.org/gene/10090:Hes6 ^@ http://purl.uniprot.org/uniprot/Q9JHE6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences. Also suppresses HES1-mediated inhibition of the heterodimer formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-regulate transcription in its presence. Promotes cell differentiation.|||Expressed in both embryo and adult. Expression in the embryo is detected from 8.5 dpc. In the retina, expressed at high levels at postnatal 0 dpc. Expression in brain and retina decreases postnatally but still detectable in adult.|||Expressed in both undifferentiated and differentiated cells. High levels of expression are observed in several embryonic tissues including the nervous system, muscle and thymus. In the nervous system, initially expressed in the closing neural tube, then in the spinal cord, cranial and dorsal root ganglia, and brain neuroepithelium. Also expressed in epithelial cells of the embryonic respiratory, urinary and digestive systems. In the limb buds, expressed in skeletal muscle and presumptive tendons.|||Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).|||Nucleus|||The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.|||Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family (By similarity). Interacts with HES1. http://togogenome.org/gene/10090:Or52j3 ^@ http://purl.uniprot.org/uniprot/E9PYB3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Acot3 ^@ http://purl.uniprot.org/uniprot/Q53YL1|||http://purl.uniprot.org/uniprot/Q9QYR7 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:15007068, PubMed:16940157). Mainly active on long-chain acyl-CoAs (PubMed:15007068, PubMed:16940157). May have a function in termination of beta-oxidation of fatty acids (PubMed:16940157).|||In the liver and kidney, by peroxisome proliferator (such as Clofibrate) treatment, via the peroxisome proliferator-activated receptors (PPARs) or fasting for 24 hours.|||Peroxisome|||Widely expressed. Highly expressed in the kidney, expressed at low level in the liver. Isoform 2 is expressed in the kidney, but not in the liver. Isoform 1 is liver-specific (PubMed:10567408). Highly expressed in kidney (at protein level) (PubMed:15007068). http://togogenome.org/gene/10090:Anks1 ^@ http://purl.uniprot.org/uniprot/A0A3B2W7H4|||http://purl.uniprot.org/uniprot/P59672|||http://purl.uniprot.org/uniprot/Q3UHP6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell projection|||Cytoplasm|||Interacts (via SAM domain) with EPHA2 (via SAM domain) (By similarity). Interacts with EPHA8; EPHA8 kinase activity-independent but stimulated by EPHA8 ubiquitination (PubMed:17875921). Interacts (via SAM domain) with EPHA6 (via SAM domain) (PubMed:29749928).|||Phosphorylated on tyrosine residues in response to EGF and PDGF.|||Regulator of different signaling pathways. Regulates EPHA8 receptor tyrosine kinase signaling to control cell migration and neurite retraction. http://togogenome.org/gene/10090:Fbxw4 ^@ http://purl.uniprot.org/uniprot/Q9JMJ2 ^@ Function|||Subunit ^@ Part of a SCF (SKP1-cullin-F-box) protein ligase complex (Probable). Interacts with POUF51 (PubMed:29153991).|||Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. Likely to be involved in key signaling pathways crucial for normal limb development. May participate in Wnt signaling. http://togogenome.org/gene/10090:Lcn4 ^@ http://purl.uniprot.org/uniprot/Q24JQ8|||http://purl.uniprot.org/uniprot/Q62472 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted|||Specifically expressed in vomeronasal and posterior glands of the nasal septum, the ducts of which open into the lumen of the vomeronasal organ.|||Transport of lipophilic molecules, possible pheromone-carrier. http://togogenome.org/gene/10090:Tas2r109 ^@ http://purl.uniprot.org/uniprot/Q7M707 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Or2w2 ^@ http://purl.uniprot.org/uniprot/Q5SZS9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Alg13 ^@ http://purl.uniprot.org/uniprot/Q9D8C3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 28 family.|||Endoplasmic reticulum|||Isoform 2 may interact with ALG14.|||May be involved in protein N-glycosylation, second step of the dolichol-linked oligosaccharide pathway (By. similarity).|||Possible multifunctional enzyme with both glycosyltransferase and deubiquitinase activities. http://togogenome.org/gene/10090:Cfap141 ^@ http://purl.uniprot.org/uniprot/Q9D9D9 ^@ Function|||Subcellular Location Annotation ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Prkx ^@ http://purl.uniprot.org/uniprot/Q922R0 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.|||Binding of cAMP to the PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer. The released monomeric PRKX is then active and able to phosphorylate its substrates (By similarity).|||Cytoplasm|||Expressed in central nervous system and heart tissues in early development stages and in most organs at later stages (at protein level). Detected in embryos from 9 dpc onward with higher expression in differentiating neuronal tissues at 11.5 dpc.|||Like other cAMP-dependent protein kinases, the inactive holoenzyme is probably composed of 2 PRKX catalytic subunits and a dimer of regulatory subunits. Interacts (cAMP-dependent) specifically with the regulatory subunits PRKAR1A and PRKAR1B. Compared to other cAMP-dependent serine/threonine protein kinases, does not interact with the 2 other PKA regulatory subunits PRKAR2A and PRKAR2B. Interacts with PIN1 (via WW domain). Interacts with cAMP-dependent protein kinase inhibitor/PKI proteins; inhibits PRKX (By similarity). Interacts with GPKOW (By similarity). Interacts with SMAD6 (By similarity). Interacts with PKD1; involved in differentiation and controlled morphogenesis of the kidney (By similarity).|||Nucleus|||Phosphorylated; autophosphorylates in vitro.|||Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation.|||Widely expressed. http://togogenome.org/gene/10090:Shq1 ^@ http://purl.uniprot.org/uniprot/Q7TMX5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SHQ1 family.|||Directly interacts with DKC1 alone, but not in the context of the core trimer composed of DKC1, NOP10 and NHP2, nor in the presence of NAF1. Does not interact with NAF1 (By similarity).|||Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA.|||cytosol|||nucleoplasm http://togogenome.org/gene/10090:Nav1 ^@ http://purl.uniprot.org/uniprot/Q8CH77 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nav/unc-53 family.|||Expressed in heart and brain. Present in brain (at protein level). In adult brain, found almost exclusively in areas of secondary neurogenesis from the hippocampus and the subventricular zone.|||Expressed in neural structures at 10 dpc. At 13 dpc and 15 dpc, highly expressed in neural tube, somites, heart and dispersed cells in tongue and face. At P5, widely expressed through the central nervous system in post-mitotic post-migratory zones. Brain expression decreases rapidly from P5 to P21 (at protein level).|||Interacts with tubulin.|||May be involved in neuronal migration.|||cytoskeleton http://togogenome.org/gene/10090:Lrat ^@ http://purl.uniprot.org/uniprot/Q9JI60 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the H-rev107 family.|||Endoplasmic reticulum membrane|||Hepatic stellate cells and endothelial cells (at protein level).|||Inhibited by all-trans-retinyl alpha-bromoacetate and N-boc-L-biocytinyl-11-aminoundecane chloro-methyl ketone (BACMK).|||Knockout mice are viable (PubMed:25416279). Knockout mice at one month of age show loss of nearly all cone photoreceptors in the central and ventral retina (PubMed:25416279). Surviving cone cells show severe degeneration, the dorsal retinal also exhibits a significant reduction in cone photoreceptors (PubMed:25416279). At one month of age rod photoreceptors show shorter outer segments (PubMed:25416279). Nearly all cone photoreceptors are lost by six months of age (PubMed:25416279). Remaining cone cells show disrupted structures with the majority showing abnormal cell bodies or lack of an outer segment (PubMed:25416279).|||LRAT activity is up-regulated by dietary vitamin A (By similarity). Under conditions of vitamin A depletion, LRAT expression in the liver is induced by retinoic acid.|||Rough endoplasmic reticulum|||Transfers the acyl group from the sn-1 position of phosphatidylcholine to all-trans retinol, producing all-trans retinyl esters. Retinyl esters are storage forms of vitamin A (PubMed:28758396). LRAT plays a critical role in vision (By similarity). It provides the all-trans retinyl ester substrates for the isomerohydrolase which processes the esters into 11-cis-retinol in the retinal pigment epithelium; due to a membrane-associated alcohol dehydrogenase, 11 cis-retinol is oxidized and converted into 11-cis-retinaldehyde which is the chromophore for rhodopsin and the cone photopigments (By similarity). Required for the survival of cone photoreceptors and correct rod photoreceptor cell morphology (PubMed:25416279).|||multivesicular body|||perinuclear region http://togogenome.org/gene/10090:Plekhg6 ^@ http://purl.uniprot.org/uniprot/Q8R0J1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cleavage furrow|||Guanine nucleotide exchange factor activating the small GTPase RHOA, which, in turn, induces myosin filament formation. Also activates RHOG. Does not activate RAC1, or to a much lower extent than RHOA and RHOG. Part of a functional unit, involving PLEKHG6, MYH10 and RHOA, at the cleavage furrow to advance furrow ingression during cytokinesis. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with EZR, required for normal macropinocytosis (By similarity).|||Interacts with MYH10. Interacts with ELMO1 and EZR (in an open conformation). Interacts with CSPP1 (By similarity).|||microvillus|||spindle http://togogenome.org/gene/10090:Fkbp5 ^@ http://purl.uniprot.org/uniprot/Q64378 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation impairs ability to promote interaction between Akt/AKT1 and PHLPP1. Deacetylation by SIRT7 promotes interaction between Akt/AKT1 and PHLPP1, leading to suppress Akt/AKT1 activation.|||Cytoplasm|||Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded. Acts as a regulator of Akt/AKT1 activity by promoting the interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1. Interacts with IKBKE and IKBKB which facilitates IKK complex assembly leading to increased IKBKE and IKBKB kinase activity, NF-kappaB activation, and IFN production.|||Inhibited by both FK506 and rapamycin.|||Nucleus|||Part of a heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B and steroid receptors (PubMed:11751894). Upon ligand binding dissociates from the complex and FKBP4 takes its place (PubMed:11751894). Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP (By similarity). Interacts with NR3C1 (PubMed:21994940). Interacts with Akt/AKT1 and PHLPP1; enhancing dephosphorylation and subsequent activation of Akt/AKT1 (By similarity). Interacts with IFI44L; this interaction modulates the kinase activity of IKBKB and IKBKE (By similarity). Interacts with IKBKB and IKBKE (By similarity).|||Widely expressed, highest levels found in the liver, skeletal muscle, kidney and thymus. Expression is regulated during adipocyte differentiation. http://togogenome.org/gene/10090:Rab4a ^@ http://purl.uniprot.org/uniprot/P56371|||http://purl.uniprot.org/uniprot/Q3ULK1 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasm|||Early endosome membrane|||Expressed in the central nervous system, including cortex, cerebellum, midbrain and spinal cord, and in the kidney, lung, liver and spleen.|||Interacts with SGSM1, SGSM2 and SGSM3 (PubMed:17509819). Interacts with RAB11FIP1, RABEP1, ZFYVE20 and RUFY1 (PubMed:11172003). Interacts (membrane-bound form) with NDRG1; the interaction involves NDRG1 in vesicular recycling of E-cadherin. Interacts (in GTP-bound form) with GRIPAP1 (via N-terminus). Interacts with RABEP1 and RBSN (By similarity). Does not interact with HPS4 (By similarity). Does not interact with HPS4 (PubMed:20048159). Interacts with RABEP2; this interaction may mediate VEGFR2 cell surface expression (By similarity).|||It is uncertain whether Met-1 or Met-6 is the initiator.|||Membrane|||Phosphorylated by CDK1 kinase during mitosis.|||Protein transport.|||Recycling endosome membrane|||Serotonylation of Gln-72 by TGM2 during activation and aggregation of platelets leads to constitutive activation of GTPase activity.|||Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:14697203). Involved in protein transport. Plays a role in vesicular traffic. Mediates VEGFR2 endosomal trafficking to enhance VEGFR2 signaling (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (PubMed:14697203). http://togogenome.org/gene/10090:Blzf1 ^@ http://purl.uniprot.org/uniprot/Q8R2X8 ^@ Caution|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.|||Golgi apparatus membrane|||Interacts with GORASP2 (PubMed:11739401, PubMed:28049725). Interacts with the GTP-bound form of RAB2, but not with other Golgi Rab proteins (PubMed:11739401). Identified in a complex with RAB2 and GORASP2 (PubMed:11739401).|||Required for normal Golgi structure and for protein transport from the endoplasmic reticulum (ER) through the Golgi apparatus to the cell surface.|||The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2.|||Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation.|||Was initially thought to be a potential transcription factor, localized in the nucleus. http://togogenome.org/gene/10090:Efemp1 ^@ http://purl.uniprot.org/uniprot/Q8BPB5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibulin family.|||Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulator of chondrocyte differentiation. In the olfactory epithelium, it may regulate glial cell migration, differentiation and the ability of glial cells to support neuronal neurite outgrowth (By similarity).|||Interacts with ECM1. Interacts with TIMP3.|||Mice are viable and have no overt phenotype at birth. However, they exhibit reduced reproductivity and an early onset of aging-associated phenotypes including reduced lifespan, decreased body mass, lordokyphosis, reduced hair growth and generalized fat, muscle and organ atrophy. They also display multiple hernias associated with a reduction of elastic fibers in facia, the thin layer of connective tissue maintaining and protecting structures throughout the body. However, there is no apparent macular degeneration.|||extracellular matrix|||extracellular space http://togogenome.org/gene/10090:Acox2 ^@ http://purl.uniprot.org/uniprot/Q9QXD1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-667 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the acyl-CoA oxidase family.|||Homodimer.|||Oxidizes the CoA esters of the bile acid intermediates di- and tri-hydroxycoprostanic acids (By similarity). Capable of oxidizing short as well as long chain 2-methyl branched fatty acids (By similarity).|||Peroxisome http://togogenome.org/gene/10090:Rras ^@ http://purl.uniprot.org/uniprot/P10833 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Interacts with PLCE1 (By similarity). Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts with OSBPL3 (By similarity). Interacts with ZDHHC19 (By similarity).|||Regulates the organization of the actin cytoskeleton. With OSPBL3, modulates integrin beta-1 (ITGB1) activity.|||S-palmitoylated by ZDHHC19, leading to increased association with membranes and with rafts/caveolae as well as enhanced cell viability. http://togogenome.org/gene/10090:Pgc ^@ http://purl.uniprot.org/uniprot/Q9D7R7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase A1 family.|||Hydrolyzes a variety of proteins.|||Secreted http://togogenome.org/gene/10090:Psme3ip1 ^@ http://purl.uniprot.org/uniprot/Q91WE2 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in skeletal muscle.|||Interacts (via C-terminus) with both free and 20S proteasome-bound forms of the proteasome activator complex subunit PSME3/PA28G; the interaction is direct.|||Nucleus|||Phosphorylation by CK2 stabilizes the interaction with PSME3.|||Promotes the association of the proteasome activator complex subunit PSME3 with the 20S proteasome and regulates its activity. Inhibits PSME3-mediated degradation of some proteasome substrates, probably by affecting their diffusion rate into the catalytic chamber of the proteasome. Also inhibits the interaction of PSME3 with COIL, inhibits accumulation of PSME3 in Cajal bodies and positively regulates the number of Cajal bodies in the nucleus.|||Shows relatively constant expression in both proliferating myoblasts and in differentiated myotubes, when assayed in C2C12 cell line (at protein level).|||Up-regulated in response to denervation-induced skeletal muscle atrophy. Induced by MYOD1. http://togogenome.org/gene/10090:Cd300ld3 ^@ http://purl.uniprot.org/uniprot/Q6SJQ5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an activating receptor inducing cytokine production in mast cells. Can act as a positive regulator of TLR9 signaling in macrophages, leading to enhanced production of pro-inflammatory cytokines.|||Belongs to the CD300 family.|||Cell membrane|||Down-regulated in macrophages by single-stranded CpG oligodeoxynucleotide stimulation.|||Early endosome|||Highly expressed in bone marrow-derived mast cells and macrophages, peripheral blood monocytes and CD11c+ cells, with weaker expression detected in CD11b cells in bone marrow and peripheral blood. Not detected in B220+ cells in bone marrow or spleen, in Thy-1.2+ or CD3+ cells in peripheral blood, spleen or thymus, or in NK1.1+ cells in spleen (at protein level). Widely expressed in various tissues including heart, liver, spleen, lung, kidney, brain, bone marrow, thymus, axillary lymph node and mesenteric lymph node. Highly expressed in macrophage cell lines J774.1 and RAW 264.7 and in mast cell line MC/9. Weak expression detected in B-lineage cell lines WEHI-231 and A20 and in dendritic cell line DC2.4. Not detected in other myeloid cell lines or T-lineage cell lines.|||Interacts with FCER1G; the interaction may be indirect. Interacts with TLR9.|||Lysosome http://togogenome.org/gene/10090:Zcwpw1 ^@ http://purl.uniprot.org/uniprot/Q6IR42 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Chromosome|||Dual histone methylation reader specific for PRDM9-catalyzed histone marks (H3K4me3 and H3K36me3) that facilitates the repair of PRDM9-induced meiotic double-strand breaks (DSBs) (PubMed:32374261, PubMed:32352380, PubMed:32744506). Essential for male fertility and spermatogenesis (PubMed:31453335, PubMed:32374261, PubMed:32352380, PubMed:32744506). Required for meiosis prophase I progression in male but not in female germ cells (PubMed:31453335).|||Male mice are sterile with complete azoospermia and reduced testis size, show impaired spermatogenesis, spermatocytes display meiotic arrest at around the zygotene to pachytene stage with incomplete homologous synapsis which is accompanied by defective DNA double-strand breaks repair (PubMed:31453335, PubMed:32374261, PubMed:32352380, PubMed:32744506). Fertility of females is normal up to mid-adulthood (5 to 6 months of age), at 3 and 6 months, ovaries exhibit healthy ovarian morphologies, however ovaries are devoid of follicles at around 8 months of age, and accordingly female mice become infertile (PubMed:31453335, PubMed:32744506). Female germ cells exhibit a successful but delayed meiosis prophase I progression (PubMed:31453335).|||Nucleus|||Testis (at protein level) (PubMed:31453335, PubMed:32352380, PubMed:32374261, PubMed:32744506). Expressed in thymus, brain, lung, ovary, oviduct and uterus (PubMed:31453335).|||The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3. http://togogenome.org/gene/10090:Asgr2 ^@ http://purl.uniprot.org/uniprot/P24721 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium is required for ligand binding.|||Expressed exclusively in hepatic parenchymal cells.|||Interacts with LASS2.|||Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.|||Membrane http://togogenome.org/gene/10090:Mtg1 ^@ http://purl.uniprot.org/uniprot/Q8R2R6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial ribosome large subunit; the association occurs in a GTP-dependent manner (By similarity).|||Belongs to the TRAFAC class YlqF/YawG GTPase family. MTG1 subfamily.|||Mitochondrion inner membrane|||Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity (By similarity). Displays mitochondrial GTPase activity (By similarity). http://togogenome.org/gene/10090:Bmyc ^@ http://purl.uniprot.org/uniprot/Q6P8Z1 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Highly expressed in epididymis. Also expressed in hypothalamus, pituitary, uterus and ovary. Low expression in testis. Not detected in heart.|||Nucleus|||Rapidly degraded via the ubiquitin-proteasome pathway.|||Seems to act as an inhibitor of cellular proliferation. http://togogenome.org/gene/10090:Dna2 ^@ http://purl.uniprot.org/uniprot/Q6ZQJ5 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by EP300, leading to stimulate the 5'-3' endonuclease, the 5'-3' helicase and DNA-dependent ATPase activities, possibly by increasing DNA substrate affinity.|||Belongs to the DNA2/NAM7 helicase family.|||Binds 1 [4Fe-4S] cluster.|||Interacts with BLM and WDHD1.|||Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function (By similarity).|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Ifnar2 ^@ http://purl.uniprot.org/uniprot/O35664 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type II cytokine receptor family.|||Cell membrane|||Heterodimer with IFNAR1; forming the receptor for type I interferon. Interacts with the transcriptional factors STAT1 and STAT2. Interacts with JAK1. Interacts with USP18; indirectly via STAT2, it negatively regulates the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and therefore type I interferon signaling.|||May be potent inhibitors of type I IFN receptor activity.|||Phosphorylated on tyrosine residues upon interferon binding. Phosphorylation at Tyr-335 or Tyr-510 are sufficient to mediate interferon dependent activation of STAT1, STAT2 and STAT3 leading to antiproliferative effects on many different cell types (By similarity).|||Secreted|||Together with IFNAR1, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response. Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another. The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (STAT1, STAT2 and STAT). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes.|||Widely expressed. Detected in liver, testis, kidney, salivary gland, thymus, brain, lung and placenta. Isoform 1, isoform 2 and isoform 3 are expressed in brain. http://togogenome.org/gene/10090:Sema6d ^@ http://purl.uniprot.org/uniprot/A2AW73|||http://purl.uniprot.org/uniprot/Q76KF0 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell membrane|||Expressed in brain and lung.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Shows growth cone collapsing activity on dorsal root ganglion (DRG) neurons in vitro. May be a stop signal for the DRG neurons in their target areas, and possibly also for other neurons. May also be involved in the maintenance and remodeling of neuronal connections (By similarity). http://togogenome.org/gene/10090:Trnau1ap ^@ http://purl.uniprot.org/uniprot/Q80VC6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM TRSPAP family.|||Cytoplasm|||Found in a complex with tRNA(Sec) (By similarity). Interacts with SEPSECS (By similarity). Component of the tRNA(Sec) complex composed at least of EEFSEC, SECISBP2, SEPHS1, SEPSECS, TRNAU1AP and tRNA(Sec). Associates with mRNP and/or polysomes.|||Involved in the early steps of selenocysteine biosynthesis and tRNA(Sec) charging to the later steps resulting in the cotranslational incorporation of selenocysteine into selenoproteins. Stabilizes the SECISBP2, EEFSEC and tRNA(Sec) complex. May be involved in the methylation of tRNA(Sec). Enhances efficiency of selenoproteins synthesis.|||Nucleus http://togogenome.org/gene/10090:Vmn2r87 ^@ http://purl.uniprot.org/uniprot/E9PZX4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zdhhc7 ^@ http://purl.uniprot.org/uniprot/Q91WU6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autopalmitoylated.|||Belongs to the DHHC palmitoyltransferase family.|||Golgi apparatus membrane|||Golgi-localized palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes (PubMed:15603741, PubMed:19001095, PubMed:23687301, PubMed:25253725). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable). Palmitoylates sex steroid hormone receptors, including ESR1, PGR and AR, thereby regulating their targeting to the plasma membrane and their function in rapid intracellular signaling upon binding of sex hormones. Palmitoylates GNAQ, a heterotrimeric G protein, regulating its dynamic localization at the plasma membrane and is thereby involved in GNAQ-dependent G protein-coupled receptor signaling pathways (PubMed:19001095). Functions also in ligand-induced cell death by regulating the FAS signaling pathway through the palmitoylation and stabilization of the receptor at the plasma membrane. In epithelial cells, palmitoylates SCRIB and regulates its localization to the plasma membrane, regulating indirectly cell polarity and differentiation. Also palmitoylates JAM3 and promotes its expression at tight junctions and regulates its function in cell migration (By similarity). Palmitoylates the glucose transporter GLUT4/SLC2A4 and controls the insulin-dependent translocation of GLUT4 to the plasma membrane (PubMed:28057756). In brain, could also palmitoylate SNAP25 and DLG4/PSD95 (PubMed:15603741, PubMed:25253725). Could also palmitoylate DNAJC5 and regulate its localization to the Golgi membrane (PubMed:18596047). Could also palmitoylate NCDN (PubMed:23687301). May play a role in follicle stimulation hormone (FSH) activation of testicular Sertoli cells (By similarity).|||Homooligomers (PubMed:17151279). Heterooligomers with ZDHHC3 (PubMed:17151279).|||Homozygous knockout mice are viable, fertile and do not display overt phenotype (PubMed:27875292). Knockout mice are hyperglycemic, glucose intolerant and develop a type II diabetic syndrome (PubMed:28057756). Zdhhc3 and Zdhhc7 double knockout mice show a perinatally lethal phenotype (PubMed:27875292).|||The DHHC domain is required for palmitoyltransferase activity.|||Ubiquitously expressed, with highest levels in liver, kidney and brain. Expressed in all brain regions. http://togogenome.org/gene/10090:Or14j10 ^@ http://purl.uniprot.org/uniprot/Q923Q6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aak1 ^@ http://purl.uniprot.org/uniprot/Q3UHJ0 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cell membrane|||Interacts (via CBD domain) with clathrin (By similarity). Interacts with AP-2 complex (By similarity). Interacts with NUMB (By similarity). Interacts with alpha-adaptin (By similarity). Interacts with EPS15 isoform 2 (By similarity). Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1 (PubMed:21464124). Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form (PubMed:21464124).|||Presynapse|||Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis. Preferentially, may phosphorylate substrates on threonine residues. Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity.|||Stimulated by clathrin.|||clathrin-coated pit http://togogenome.org/gene/10090:Gtf2ird1 ^@ http://purl.uniprot.org/uniprot/Q5XJY7|||http://purl.uniprot.org/uniprot/Q6PD35|||http://purl.uniprot.org/uniprot/Q8BP10|||http://purl.uniprot.org/uniprot/Q9JI57 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TFII-I family.|||Expressed in somites, neural tube and brain at 8-8.5 dpc. Expression remains constant from 9.5-12.5 dpc with highest expression levels in the limb buds, branchial arches, crainofacial area, brain and spinal cord.|||Interacts with the retinoblastoma protein (RB1) via its C-terminus.|||May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. May repress GTF2I transcriptional functions, by preventing its nuclear residency, or by inhibiting its transcriptional activation. May contribute to slow-twitch fiber type specificity during myogenesis and in regenerating muscles. Binds troponin I slow-muscle fiber enhancer (USE B1). Binds specifically and with high affinity to the EFG sequences derived from the early enhancer of HOXC8.|||Nucleus|||Widely expressed. http://togogenome.org/gene/10090:Tas1r1 ^@ http://purl.uniprot.org/uniprot/Q3U5H1|||http://purl.uniprot.org/uniprot/Q99PG6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family. TAS1R subfamily.|||Cell membrane|||Expressed strongly only in fungiform papillae.|||Forms heterodimers with TAS1R3.|||Membrane|||Putative taste receptor. TAS1R1/TAS1R3 responds to the umami taste stimulus (the taste of monosodium glutamate) and also to most of the 20 standard L-amino acids, but not to their D-enantiomers or other compounds. Sequence differences within and between species can significantly influence the selectivity and specificity of taste responses. http://togogenome.org/gene/10090:Bicdl1 ^@ http://purl.uniprot.org/uniprot/A0JNT9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor (PubMed:29420470, PubMed:33734450, PubMed:36071160). Component of secretory vesicle machinery in developing neurons that acts as a regulator of neurite outgrowth. Regulates the secretory vesicle transport by controlling the accumulation of Rab6-containing secretory vesicles in the pericentrosomal region restricting anterograde secretory transport during the early phase of neuronal differentiation, thereby inhibiting neuritogenesis.|||Belongs to the BICDR family.|||Highly expressed during early embryonic development. Predominantly expressed in kidney, undifferentiated neural tissue and developing eye.|||Part of a tripartite complex with dynein and dynactin, acts an adapter linking the dynein motor complex and dynactin (PubMed:29420470, PubMed:33734450, PubMed:36071160). Interacts with KIF1C. Interacts with RAB6A and RAB6B; interaction is specific to Rab6.|||Predominately expressed in early developing neurons before the stage of neurite outgrowth and elongation. Then, expression strongly declines during neuronal development.|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Tsx ^@ http://purl.uniprot.org/uniprot/P70675 ^@ Function|||Tissue Specificity ^@ May have an RNA/DNA binding role.|||Testis. http://togogenome.org/gene/10090:Septin10 ^@ http://purl.uniprot.org/uniprot/A0A0R4J233|||http://purl.uniprot.org/uniprot/A0A1W2P6J7|||http://purl.uniprot.org/uniprot/Q8C650 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential).|||Filament-forming cytoskeletal GTPase.|||Proteolytically cleaved in vitro in a calmodulin-dependent manner.|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation (By similarity). Interacts with ADGB (PubMed:35700329).|||Septins polymerize into heterooligomeric protein complexes that form filaments.|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Gabbr2 ^@ http://purl.uniprot.org/uniprot/Q80T41 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR1.|||Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.|||Cell membrane|||Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:10075644). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10075644). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (By similarity). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (By similarity).|||Heterodimer of GABBR1 and GABBR2 (PubMed:10075644). Homodimers may form, but are inactive (By similarity). Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Csde1 ^@ http://purl.uniprot.org/uniprot/Q91W50 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of a multi subunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Interacts with STRAP. Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, HNRPD and SYNCRIP. The interaction with PABPC1 is direct and RNA-independent. Interacts with EIF4ENIF1/4E-T.|||Cytoplasm|||P-body|||RNA-binding protein involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Required for efficient formation of stress granules.|||Stress granule http://togogenome.org/gene/10090:Egfl6 ^@ http://purl.uniprot.org/uniprot/Q9JJZ5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the nephronectin family.|||Detected in early lateral dermatome and in all dermatome derivatives. Expressed at the basement membrane of embryonic skin and developing hair follicles. At 16.5 dpc, present in lung epithelium, and developing oral and tooth germ epithelia (at protein level).|||Expressed at basement membrane of pelage follicles (at protein level).|||May bind integrin alpha-8/beta-1 and play a role in hair follicle morphogenesis. Promotes matrix assembly.|||basement membrane http://togogenome.org/gene/10090:Rad18 ^@ http://purl.uniprot.org/uniprot/E9Q392|||http://purl.uniprot.org/uniprot/Q8CDH2|||http://purl.uniprot.org/uniprot/Q8CED3|||http://purl.uniprot.org/uniprot/Q9QXK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RAD18 family.|||E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity.|||Expressed in thymus, spleen, brain, and ovary.|||Homodimer. Interacts with UBE2A and UBE2B, one homodimer binding one molecule of UBE2B. Interacts with HLTF. Interacts with SHPRH. Interacts with SPRTN; leading to enhance chromatin association of RAD18 and RAD18-mediated PCNA ubiquitination and translesion DNA synthesis. Interacts (via C-terminus and phosphorylated form) with SLF1 (via BRCT domains); this interaction is required for efficient repair of UV-induced DNA damage. Interacts with SLF2. Interacts with SMC5; this interaction is increased in a SLF1 or SLF2-dependent manner.|||Nucleus|||centrosome http://togogenome.org/gene/10090:Tmem256 ^@ http://purl.uniprot.org/uniprot/Q5F285 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM256 family.|||Membrane http://togogenome.org/gene/10090:Arl4d ^@ http://purl.uniprot.org/uniprot/Q99PE9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||Cell membrane|||Cytoplasm|||Interacts with CYTH2; the interaction is direct and ARL4D GTP-dependent. Does not interact with ARL4D (By similarity).|||Nucleus|||Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Recruits CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane in GDP-bound form (By similarity).|||nucleolus http://togogenome.org/gene/10090:Cabin1 ^@ http://purl.uniprot.org/uniprot/G3X8Q1|||http://purl.uniprot.org/uniprot/Q6PFH4|||http://purl.uniprot.org/uniprot/Q80X22 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Vmn1r29 ^@ http://purl.uniprot.org/uniprot/Q9EQ41 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Irgm1 ^@ http://purl.uniprot.org/uniprot/J7NUP1|||http://purl.uniprot.org/uniprot/Q60766 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.|||Cell membrane|||Expressed in lung and primary macrophages.|||Golgi apparatus membrane|||Immunity-related GTPase that plays important roles in innate immunity and inflammatory response (PubMed:11457893, PubMed:14576437, PubMed:14707092, PubMed:15908352, PubMed:16339555, PubMed:17911638, PubMed:17982087, PubMed:19620982, PubMed:19920210). Acts as a dynamin-like protein that binds to intracellular membranes and promotes remodeling and trafficking of those membranes (PubMed:19620982, PubMed:27098192). Required for clearance of acute protozoan and bacterial infections by interacting with autophagy and lysosome regulatory proteins, thereby promoting the fusion of phagosomes with lysosomes for efficient degradation of cargo including microbes (PubMed:11457893, PubMed:14576437, PubMed:15607973, PubMed:14707092, PubMed:15908352, PubMed:16339555, PubMed:17982087, PubMed:19620982, PubMed:19920210, PubMed:24751652, PubMed:21757726, PubMed:22874556, PubMed:32453761). Regulates selective autophagy, including xenophagy and mitophagy, both directly and indirectly (PubMed:15607973, PubMed:21757726). Directly regulates autophagy by acting as a molecular adapter that promotes the coassembly of the core autophagy machinery to mediate antimicrobial defense: Irgm1 (1) activates AMPK, which in turn phosphorylates ULK1 and BECN1 to induce autophagy, (2) promotes the coassembly of ULK1 and BECN1, enhancing BECN1-interacting partners and (3) influences the composition of the BECN1 complex, by competing with the negative regulators BCL2 and RUBCN, to trigger autophagy (By similarity). Also activates autophagy by promoting recruitment of STX17 to autophagosomes (By similarity). In collaboration with ATG8 proteins, regulate lysosomal biogenesis, a fundamental process for any autophagic pathway, by promoting TFEB dephosphorylation (By similarity). Also modulates autophagy by assisting with autophagosome formation and preventing lysosomal deacidification (PubMed:21757726). Regulates autophagy by affecting mitochondrial fusion and fission (PubMed:24751652). Also involved in M1 macrophage activation for the production of proinflammatory cytokines (PubMed:15908352, PubMed:27439214, PubMed:27443879). While activating autophagy, acts as a key negative regulator of the inflammatory and interferon responses both by (1) promoting mitophagy and (2) mediating autophagy-dependent degradation of effectors of the inflammatory response (PubMed:30612879, PubMed:34467632, PubMed:33510463). Promotes degradation of damaged and IFNG/IFN-gamma-stressed mitochondria via mitophagy, preventing cytosolic release of ligands that activate inflammation (PubMed:32715615, PubMed:33510463). Negatively regulates interferon-signaling in hematopoietic stem cells, preserving hematopoietic stem cell number and function (PubMed:18371424, PubMed:21633090). Promotes expansion of activated CD4(+) T-cells by inhibiting IFNG/IFN-gamma signaling, thereby preventing Ifng-mediated cell death of CD4(+) T-cells (PubMed:18806793). Acts as a suppressor of inflammation by promoting recruitment of inflammation effectors, such as CGAS, RIGI/RIG-I and NLRP3, to autophagosome membranes, leading to their SQSTM1/p62-dependent autophagic degradation (By similarity). Also directly inhibits assembly of the NLRP3 inflammasome by preventing the association between NLRP3 and PYCARD (By similarity). Acts as a negative regulator of antiviral innate immune response by suppressing the RIPK2-dependent pro-inflammatory response: mediates recruitment of RIPosomes, composed of RIPK2 and NOD1 or NOD2, to autophagosome membranes, promoting their SQSTM1/p62-dependent autophagic degradation (By similarity).|||Interacts with ULK1; promoting the coassembly of ULK1 and BECN1. Interacts with BECN1; enhancing BECN1-interacting partners and influencing the composition of the BECN1 complex. Interacts with ATG16L1. Interacts with NOD2; promoting Irgm1 'Lys-63'-linked polyubiquitination, which is required for interactions with the core autophagy factors (By similarity). Interacts with STX17; promoting STX17 recruitment to autophagosomes (By similarity). Interacts with ATG8 proteins (GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C); promoting STX17 recruitment to autophagosomes (By similarity). Interacts with TFEB; promoting association between TFEB and PPP3CB and TFEB dephosphorylation (By similarity). Interacts with PPP3CB; promoting association between TFEB and PPP3CB and TFEB dephosphorylation (By similarity). Interacts with NLRP3; preventing NLRP3 inflammasome assembly and promoting SQSTM1/p62-dependent autophagic degradation of NLRP3 (By similarity). Interacts with CGAS; promoting SQSTM1/p62-dependent autophagic degradation of CGAS (By similarity). Interacts with RIGI/RIG-I; promoting SQSTM1/p62-dependent autophagic degradation of RIGI/RIG-I (By similarity). Interacts with NOD1; promoting SQSTM1/p62-dependent autophagic degradation of RIGI/RIG-I (By similarity). Interacts with NOD2; promoting SQSTM1/p62-dependent autophagic degradation of RIGI/RIG-I (By similarity). Interacts with RIPK2; promoting SQSTM1/p62-dependent autophagic degradation of RIGI/RIG-I (By similarity). Interacts with PIK3CA (PubMed:19620982).|||Late endosome membrane|||Lipid droplet|||Lysosome membrane|||Mice do not show obvious abnormalities, but are more susceptible to infection by S.typhimurium, T.cruzi, T.gondii, L.monocytogenes, C.rodentium and M.tuberculosis (PubMed:11457893, PubMed:14576437, PubMed:32453761). Upon infection, alterations of blood elements occur including lymphopenia, anemia, and thrombocytopenia (PubMed:11457893, PubMed:14576437, PubMed:18371424). Mice become anemic and neutropenic as a result of chronic infection, and their hematopoietic stem cells are defective in the ability to reconstitute the blood of a Bone marrow-depleted host (PubMed:18371424). Mice display impaired expansion of activated CD4(+) T-cell population: defects are caused by Infg-mediated cell death of CD4(+) T-cells (PubMed:18806793). Mice also show increased inflammation with autoimmune features (PubMed:28154172, PubMed:28814662, PubMed:30612879, PubMed:32715615, PubMed:33510463). Macrophages show an increased production of proinflammatory cytokines associated with marked metabolic changes, characterized by increased glycolysis and an accumulation of long chain acylcarnitines (PubMed:28154172). Mice display autoimmune disorder reminiscent of Sjogren's syndrome, characterized by up-regulation of type I interferons (PubMed:28814662). Type I interferonopathy, characterized by up-regulation of type I interferons, is caused by activation of inflammation effectors, such as CGAS and NLRP3 (PubMed:30612879, PubMed:32715615, PubMed:33510463). Mice show an increased antiviral innate immune response and are highly resistant to chikungunya virus (CHIKV) infection (PubMed:34467632). Mice lacking both Irgm1 and Igtp/Irgm3 display resistance to Mycobacterium tuberculosis infection compared to Irgm1 mice that are highly susceptible to infection (PubMed:36629440). Mice lacking Irgm1, Irgm2 and Igtp/Irgm3 (panIrgm mice) show resistance against M.tuberculosis one month post-infection; then, panIrgm mice display higher bacterial burden and altered cytokine during late stage of infection, leading to increased mortality (PubMed:36629440).|||Mitochondrion membrane|||Palmitoylated on C-terminal Cys residues (PubMed:24751652). Palmitoylation, together with the alpha-K amphipathic helix, which binds phosphatidylinositol, mediate binding to membranes (PubMed:24751652).|||The alpha-K amphipathic helix mediates targeting to the phagosome membrane via binding to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3).|||Ubiquitinated via 'Lys-63'-linked polyubiquitination in a NOD2-dependent process. 'Lys-63'-linked polyubiquitination is required for interactions with the core autophagy factors (By similarity). Ubiquitination at Lys-270 by the DCX(WDR77) complex, also named CLR4(WDR77) complex, in intestinal cells, leading to its degradation by the proteasome (PubMed:35197566).|||Up-regulated by LPS and IFNG (at protein level) (PubMed:7561525, PubMed:11457893, PubMed:14576437, PubMed:15294976, PubMed:17911638). Up-regulated upon infection by various pathogens including T.cruzi, T.gondii, L.monocytogenes, M.tuberculosis and murine cytomegalovirus (PubMed:14707092, PubMed:16339555).|||autophagosome membrane|||phagocytic cup|||phagosome membrane http://togogenome.org/gene/10090:Neurod6 ^@ http://purl.uniprot.org/uniprot/P48986|||http://purl.uniprot.org/uniprot/Q3UN97|||http://purl.uniprot.org/uniprot/Q5M8T7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates E box-dependent transcription in collaboration with TCF3/E47. May be a trans-acting factor involved in the development and maintenance of the mammalian nervous system. Transactivates the promoter of its own gene.|||Efficient DNA binding requires dimerization with another bHLH protein.|||Nucleus|||Specific to the nervous system of both embryos and adults. Highest levels in the cortical plate of the cerebrum. http://togogenome.org/gene/10090:Nfe2l1 ^@ http://purl.uniprot.org/uniprot/Q3U5L0|||http://purl.uniprot.org/uniprot/Q3UFI8|||http://purl.uniprot.org/uniprot/Q3V3M1|||http://purl.uniprot.org/uniprot/Q61985|||http://purl.uniprot.org/uniprot/Q6GTN8 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. CNC subfamily.|||CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses (PubMed:10601325, PubMed:11342101, PubMed:23144760, PubMed:16872277, PubMed:21911472, PubMed:23816881, PubMed:29149604). Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response (PubMed:12808106, PubMed:15738389, PubMed:23144760, PubMed:16872277, PubMed:21911472, PubMed:23816881). Activates or represses expression of target genes, depending on the context (PubMed:12808106, PubMed:15738389, PubMed:23144760, PubMed:16872277, PubMed:21911472, PubMed:23816881). Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess, such as CD36 (PubMed:29149604). In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (PubMed:29149604). Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1 and MT2 (PubMed:10601325, PubMed:11342101, PubMed:12968018, PubMed:15738389, PubMed:18826952). Plays an essential role during fetal liver hematopoiesis: probably has a protective function against oxidative stress and is involved in lipid homeostasis in the liver (PubMed:9501099, PubMed:12808106, PubMed:15738389, PubMed:18826952, PubMed:22586274). Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits (PubMed:20385086, PubMed:21536885, PubMed:23816881). Also involved in regulating glucose flux (PubMed:25041126). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (By similarity). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts (PubMed:17510056).|||Cleaved at Leu-104 by the aspartyl protease DDI2 following retrotranslocation, releasing the protein from the endoplasmic reticulum membrane and forming the transcription factor NRF1 that translocates into the nucleus. Ubiquitination is prerequisite for cleavage by aspartyl protease DDI2.|||Cytoplasm|||Embryonic lethality: embryos progress normally to the late egg cylinder stage at approximately 6.5 days post coitus (dpc), but development is arrested before 7.5 dpc (PubMed:9087432, PubMed:9501099). Mutant embryos fail to form a primitive streak and lack detectable mesoderm (PubMed:9087432). Homozygous embryos suffer from anemia as a result of abnormal fetal liver erythropoiesis (PubMed:9501099). No defect in globin gene expression are detected; abnormal red cell production being the result of a defect in the fetal liver microenvironment specific for erythroid cells (PubMed:9501099). Mice lacking both Nfe2l1 and Nfe2l2 die early between embryonic days 9 and 10 and exhibit extensive apoptosis due to marked oxidative stress in cells that is indicated by elevated intracellular reactive oxygen species levels and cell death (PubMed:12968018). Conditional knockout mice lacking Nfe2l1 in the liver do not show any liver damage when they are maintained in an unstressed condition (PubMed:15738389). In oxidative stress condition, they develop hepatic cancer following steatosis, apoptosis, necrosis, inflammation, and fibrosis (PubMed:15738389). Hepatocyte-specific deletion causes liver damage resembling the human disease non-alcoholic steatohepatitis (PubMed:18826952). Liver of conditional knockout mice lacking Nfe2l1 show massive hepatic cholesterol accumulation and damage due to inability to mediate response to cholesterol excess (PubMed:29149604). Conditional knockout mice lacking Nfe2l1 in the brain show proteasome impairment and progressive degeneration in cortical neurons (PubMed:21554501, PubMed:21536885).|||Endoplasmic reticulum membrane|||Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (PubMed:20385086, PubMed:21536885, PubMed:23816881, PubMed:29149604). Constitutes a precursor of the transcription factor NRF1. Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20385086, PubMed:21536885, PubMed:23816881, PubMed:29149604). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 (PubMed:29149604). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36 (PubMed:29149604). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (PubMed:20385086, PubMed:21536885, PubMed:23816881).|||Interacts (via CPD region) with FBXW7; leading to its ubiquitination and degradation (PubMed:21953459). Interacts with SYVN1/HRD1; leading to its ubiquitination and degradation (PubMed:21911472). Interacts (when ubiquitinated) with DDI2; leading to its cleavage (By similarity).|||Interacts (via the bZIP domain) with small MAF protein (MAFF, MAFG or MAFK); required for binding to antioxidant response elements (AREs) on DNA (PubMed:11342101, PubMed:18990090, PubMed:23144760). Interacts (via Destruction motif) with BTRC; leading to its ubiquitination and degradation (PubMed:21911472). Interacts with CEBPB; the heterodimer represses expression of DSPP during odontoblast differentiation (By similarity). Interacts with MOTS-c, a peptide produced by the mitochondrially encoded 12S rRNA MT-RNR1 (By similarity).|||Interacts with KEAP1.|||Isoform 1: Widely expressed including kidney, brown fat, white fat, large intestine, small intestine, stomach, lung, brain and liver (PubMed:23144760). Isoform 1: Expressed in mouse embryonic fibroblasts (MEF) (PubMed:23144760). Isoform 2: Widely expressed including kidney, brown fat, white fat, large intestine, small intestine, stomach, lung, brain and liver (PubMed:23144760). Isoform 2: levels in white fat, lung and liver are increased compared to isoform 1 (at protein level) (PubMed:23144760). Isoform 2: levels are elevated in brown fat and brain, but are reduced in liver compared to isoform 1 levels (PubMed:23144760). Isoform 2: Expressed in mouse embryonic fibroblasts (MEF) (PubMed:23144760).|||Its topology is subject to discussion. According to some groups, it has a single-pass type II membrane protein in normal conditions and is retrotranslocated into a single-pass type III membrane protein in response to stress. According to other reports, it is integrated into the endoplasmic reticulum membrane via multiple membrane-spanning alpha-helices (PubMed:20629635, PubMed:26268886).|||N-glycosylated in normal conditions, when it has a single-pass type II membrane protein topology, with the DNA-binding domain facing the endoplasmic reticulum lumen (PubMed:17705787, PubMed:18990090). Deglycosylated during retrotranslocation to the cytosolic side of the membrane, to have a single-pass type III membrane protein topology with the major part of the protein facing the cytosol (By similarity).|||Nucleus|||Phosphorylation by CK2 at Ser-497 inhibits transcription factor activity, possibly by affecting DNA-binding activity (PubMed:9580677, PubMed:23816881). Phosphorylation at Ser-568 is required for interaction with CEBPB (By similarity).|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||The cholesterol recognition/amino acid consensus (CRAC) region directly binds cholesterol, as well as campesterol and 27-hydroxycholesterol (PubMed:29149604). Has much lower affinity for epicholesterol (PubMed:29149604).|||Transcription factor that binds the antioxidant response elements (ARE) consensus sequence on promoters and activates their expression.|||Transcription factor that binds the extended kappa 3 site of the TNF-alpha promoter after Fc gamma RIII stimulation and participates in the induction of this cytokine (PubMed:9580677).|||Ubiquitinated by the SCF(BTRC) complex in the nucleus, leading to its degradation by the proteasome.|||Ubiquitinated by the SCF(FBXW7) complex and SYVN1/HRD1, leading to its degradation by the proteasome (PubMed:21953459, PubMed:21911472). Ubiquitinated during retrotranslocation to the cytosolic side of the membrane: ubiquitination does not lead to degradation and is required for processing by the aspartyl protease DDI2 and subsequent release from the endoplasmic reticulum membrane (By similarity).|||Was initially thought to be either inactive as transcription factor or to repress transcriptional activation mediated by other isoforms (PubMed:9580677). The presence of the transmembrane region at the N-terminus may explain the inability to observe transcription factor activity. http://togogenome.org/gene/10090:Tfap2c ^@ http://purl.uniprot.org/uniprot/A0A023UF19|||http://purl.uniprot.org/uniprot/Q3ULB3|||http://purl.uniprot.org/uniprot/Q61312 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AP-2 family.|||Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with WWOX. Interacts with UBE2I (By similarity). Interacts with CITED4. Interacts with KCTD1; this interaction represses transcription activation. Interacts with CITED2 (via C-terminus); the interaction stimulates TFAP2B-transcriptional activity. Interacts with MTA1 (By similarity).|||During retinoic acid-mediated differentiation.|||Expressed in lung, ovary and testis. Expressed in most squamous epithelia. Also, detected in several exocrine glands including the prostate, the preputial and salivary glands, serous glands of the tongue and ocular harderian glands.|||Nucleus|||Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC.|||Sumoylated on Lys-10; which inhibits transcriptional activity.|||The PPxY motif mediates interaction with WWOX. http://togogenome.org/gene/10090:Suclg2 ^@ http://purl.uniprot.org/uniprot/Q9Z2I8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the succinate/malate CoA ligase beta subunit family. GTP-specific subunit beta subfamily.|||Binds 1 Mg(2+) ion per subunit.|||GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.|||Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for GTP.|||Mitochondrion http://togogenome.org/gene/10090:Hs3st3b1 ^@ http://purl.uniprot.org/uniprot/Q9QZS6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 1 family.|||Golgi apparatus membrane|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Catalyzes the O-sulfation of glucosamine in IdoUA2S-GlcNS and also in IdoUA2S-GlcNH2. Unlike HS3ST1/3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate (By similarity). http://togogenome.org/gene/10090:Or5w1 ^@ http://purl.uniprot.org/uniprot/Q7TR43 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Brap ^@ http://purl.uniprot.org/uniprot/Q99MP8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with the nuclear localization signal of BRCA1 and with the N-terminal of KSR1. The C-terminal portion of BRCA1 interacts with DDB1.|||Isoform 2 is highly expressed in testis, lower levels in brain, heart, lung, stomach, colon, uterus, liver and kidney. Isoform 1 is only expressed in the testis. Isoform 2 is predominant over isoform 1 in both fetal and adult testis.|||Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination resulting in the release of inhibition of Raf/MEK complex formation. May also act as a cytoplasmic retention protein with a role in regulating nuclear transport (By similarity). http://togogenome.org/gene/10090:Ppcdc ^@ http://purl.uniprot.org/uniprot/Q8BZB2 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the HFCD (homooligomeric flavin containing Cys decarboxylase) superfamily.|||Binds 1 FMN per subunit.|||Catalyzes the decarboxylation of the cysteine moiety of 4-phosphopantothenoylcysteine to form 4'-phosphopantotheine and this reaction forms part of the biosynthesis of coenzyme A.|||Homotrimer. http://togogenome.org/gene/10090:Scgb2b2 ^@ http://purl.uniprot.org/uniprot/G5E8B4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Aqp12 ^@ http://purl.uniprot.org/uniprot/Q3V2I1|||http://purl.uniprot.org/uniprot/Q8CHJ2 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Aquaporins facilitate the transport of water and small neutral solutes across cell membranes.|||Belongs to the MIP/aquaporin (TC 1.A.8) family. AQP11/AQP12 subfamily.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Restricted to pancreatic acinar cells. http://togogenome.org/gene/10090:Col27a1 ^@ http://purl.uniprot.org/uniprot/Q5QNQ9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fibrillar collagen family.|||Expressed in 14.5 dpc in several cartilaginous structures including anlagen of several bones and the developing lungs as well as in the eye, ear and colon. First detectable at 12.5 dpc. At 14.5 dpc localizes to cartilage, developing dermis, cornea, the inner limiting membrane of the retina, and major arteries of the heart. At 18.5 dpc appears restricted mainly to cartilage where expression continued into adulthood.|||Highly expressed in cartilage, eye and ear.|||Plays a role during the calcification of cartilage and the transition of cartilage to bone.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Aard ^@ http://purl.uniprot.org/uniprot/Q811W1 ^@ Developmental Stage|||Tissue Specificity ^@ Expressed early in testis differentiation specifically in Sertoli cells of the developing testis cords.|||Preferentially expressed in testis both in embryo and adult. Expressed at much lower level in other tissues. http://togogenome.org/gene/10090:Slc25a18 ^@ http://purl.uniprot.org/uniprot/Q9DB41 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Incomplete sequence.|||Mitochondrion inner membrane|||Responsible for the transport of glutamate from the cytosol into the mitochondrial matrix with the concomitant import of a proton (symport system). http://togogenome.org/gene/10090:Crybg3 ^@ http://purl.uniprot.org/uniprot/A0A384DV78|||http://purl.uniprot.org/uniprot/Q80W49 ^@ Similarity ^@ Belongs to the beta/gamma-crystallin family. http://togogenome.org/gene/10090:Ptpn22 ^@ http://purl.uniprot.org/uniprot/P29352 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules (By similarity). Associates with and probably dephosphorylates CBL (By similarity). Dephosphorylates LCK at its activating 'Tyr-394' residue (By similarity). Dephosphorylates ZAP70 at its activating 'Tyr-492' residue (By similarity). Dephosphorylates the immune system activator SKAP2 (By similarity). Positively regulates toll-like receptor (TLR)-induced type 1 interferon production (PubMed:23871208). Promotes host antiviral responses mediated by type 1 interferon (PubMed:23871208). Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy (PubMed:23991106). Acts as an activator of NLRP3 inflammasome assembly by mediating dephosphorylation of 'Tyr-861' of NLRP3 (PubMed:27043286). Dephosphorylates phospho-anandamide (p-AEA), an endocannabinoid to anandamide (also called N-arachidonoylethanolamide) (PubMed:16938887).|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.|||Brain (at protein level) (PubMed:16938887). Spleen, thymus, lymph node and bone marrow (PubMed:1373816).|||By lipopolysaccharides (LPS).|||Cytoplasm|||Interacts with CBL (By similarity). Interacts with CSK (PubMed:8890164, PubMed:11685249). Interacts with LPXN (PubMed:15786712). Interacts with TRAF3 (via MATH domain); the interaction promotes TRAF3 polyubiquitination (PubMed:23871208).|||Knockout reduces the conversion of phosphoanandamide (p-AEA) to AEA in the brain.|||Phosphorylation on Ser-35 by PKC/PRKCD abrogates its ability to dephosphorylate and inactivate the SRC family kinases. http://togogenome.org/gene/10090:Defa23 ^@ http://purl.uniprot.org/uniprot/Q5G866 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Cela1 ^@ http://purl.uniprot.org/uniprot/Q91X79 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Elastase subfamily.|||Binds 1 Ca(2+) ion per subunit.|||Secreted|||Serine proteases that hydrolyze many proteins in addition to elastin. http://togogenome.org/gene/10090:Or11g7 ^@ http://purl.uniprot.org/uniprot/E9PV79 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or6c206 ^@ http://purl.uniprot.org/uniprot/Q7TRI3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhov ^@ http://purl.uniprot.org/uniprot/Q8VDU1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Endosome membrane|||Interacts with PAK2.|||Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway. http://togogenome.org/gene/10090:Plk3 ^@ http://purl.uniprot.org/uniprot/Q6P571 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily. http://togogenome.org/gene/10090:Ppp1r9b ^@ http://purl.uniprot.org/uniprot/Q6R891 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Nucleus|||Possibly exists as a homodimer, homotrimer or a homotetramer. Interacts with F-actin, PPP1CA, neurabin-1, TGN38 and D(2) dopamine receptor. Interacts with RGS1, RGS2, RGS4, RGS19 and ADRA1B, ADRA2A, ADRA2B, ADRA2C, CDKN2A, PPP1R2, RASGFR1 and TIAM1. Interacts (via C-terminus) with SPATA13 (via C-terminal tail) (By similarity). Interacts with DCLK2. Interacts with ADRA2B (By similarity).|||Postsynaptic density|||Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1. Required for hepatocyte growth factor (HGF)-induced cell migration (By similarity).|||Stimulation of D1 (but not D2) dopamine receptors induces Ser-94 phosphorylation. Dephosphorylation of Ser-94 is mediated mainly by PP1 and to a lesser extent by PP2A. Phosphorylation of spinophilin disrupts its association with F-actin, but does not affect its binding to PP1 (By similarity).|||The PP1 binding region is natively unstructured, upon PP1 binding, it acquires structure, blocks a substrate-binding site, and restricts PP1 phosphatase specificity to a subset of substrates.|||adherens junction|||cytoskeleton|||dendritic spine|||filopodium|||lamellipodium|||ruffle membrane http://togogenome.org/gene/10090:Dohh ^@ http://purl.uniprot.org/uniprot/Q99LN9 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity ^@ Belongs to the deoxyhypusine hydroxylase family.|||Binds 2 Fe(2+) ions per subunit.|||Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate produced by deoxyhypusine synthase/DHPS on a critical lysine of the eukaryotic translation initiation factor 5A/eIF-5A. This is the second step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function.|||Embryonic lethal between E3.5 and E9.5. http://togogenome.org/gene/10090:ND4L ^@ http://purl.uniprot.org/uniprot/P03903|||http://purl.uniprot.org/uniprot/Q9MD77 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 4L family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:H3c15 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Acot7 ^@ http://purl.uniprot.org/uniprot/Q91V12 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both HotDog ACOT-type hydrolase domains are required for efficient activity.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (Probable). Preferentially hydrolyzes palmitoyl-CoA, but has a broad specificity acting on other fatty acyl-CoAs with chain-lengths of C8-C18 (Probable). May play an important physiological function in brain (Probable).|||Detected in the brain as early as embryonic day (E) 11.5. The level was low until 12.5 dpc, but promptly elevated to a peak 7 days after birth. Thereafter, it declined somewhat and reached a steady-state level in adulthood. These changes in BACH expression were approximately reflected in the palmitoyl-CoA hydrolyzing activity in the developing mouse brain, and the time course was quite similar to that of microtubule-associated protein 2 (MAP2) expression. Induced during embryogenesis in association with neuronal differentiation, and persists after terminal differentiation into neurons in postnatal stages, resulting in the constitutive high expression of BACH in the adult brain in a neuron-specific manner.|||Homohexamer.|||Major isoform.|||Up-Regulated in activated macrophages.|||Widely expressed with highest levels in brain. High levels also found in thymus, large intestine and testis. Negligible in muscle and adipose tissue. In the central and peripheral nervous systems, displays a predominantly neuronal localization with highest expression in cell bodies and neurites.|||cytosol http://togogenome.org/gene/10090:Mms19 ^@ http://purl.uniprot.org/uniprot/Q9D071 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MET18/MMS19 family.|||Component of the CIA complex. In the CIA complex, interacts directly with CIAO2B and CIAO3. Component of the MMXD complex, composed of CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with CIAO2B; the interaction is direct. Interacts with ERCC2/XPD; the interaction is direct. Interacts with ERCC3/XPB and NCOA3/RAC3. Interacts with RTEL1; the interaction mediates the association of RTEL1 with the CIA complex. Interacts with BRIP1. Interacts with KIF4A; the interaction facilitates the transfer of Fe-S clusters to KIF4A to ensure proper localization of KIF4A to the mitotic machinery components. Interacts with CCDC117; the interaction is indirect (By similarity).|||Embryonically lethality before the implantation stage.|||Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity. In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target Fe/S proteins such as ERCC2/XPD, FANCJ and RTEL1, thereby playing a key role in nucleotide excision repair (NER), homologous recombination-mediated double-strand break DNA repair, DNA replication and RNA polymerase II (POL II) transcription. As a CIA complex component and in collaboration with CIAO1 and CIAO2, binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. As part of the mitotic spindle-associated MMXD complex, plays a role in chromosome segregation, probably by facilitating iron-sulfur cluster assembly into ERCC2/XPD. Together with CIAO2, facilitates the transfer of Fe-S clusters to the motor protein KIF4A, which ensures proper localization of KIF4A to mitotic machinery components to promote the progression of mitosis. Indirectly acts as a transcriptional coactivator of estrogen receptor (ER), via its role in iron-sulfur insertion into some component of the TFIIH-machinery.|||Nucleus|||Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination.|||Ubiquitously expressed with higher expression in testis.|||spindle http://togogenome.org/gene/10090:Hoxa3 ^@ http://purl.uniprot.org/uniprot/P02831 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Expressed in a spatially restricted manner in embryos 8.5 dpc, expression is limited to the CNS with an anterior boundary in the hindbrain and extending posteriorly through caudal regions of the spinal cord. The same spatial expression is seen in embryos 9.5 to 12.5 dpc.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds 5' to its own homeobox. http://togogenome.org/gene/10090:Nip7 ^@ http://purl.uniprot.org/uniprot/Q9CXK8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NIP7 family.|||Monomer. Interacts with pre-ribosome complex. May bind to RNA. Interacts with NOL8. Interacts with FTSJ3 (By similarity).|||Required for proper 34S pre-rRNA processing and 60S ribosome subunit assembly.|||nucleolus http://togogenome.org/gene/10090:Cdk5 ^@ http://purl.uniprot.org/uniprot/P49615|||http://purl.uniprot.org/uniprot/Q543F6 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cell membrane|||Cytoplasm|||Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity. Under neurotoxic stress and neuronal injury conditions, p35 is cleaved by calpain to generate p25 that hyperactivates CDK5, that becomes functionally disabled and often toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2. Interacts with AATK and GSTP1. Binds to HDAC1 when in complex with p25. Interaction with myristoylation p35 promotes CDK5 association with membranes. Both isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons (By similarity). Interacts with EPHA4; may mediate the activation of NGEF by EPHA4M. Interacts with PTK2/FAK1. The complex p35/CDK5 interacts with CLOCK (By similarity). Interacts with HTR6 (PubMed:25078650).|||Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration (By similarity).|||Nucleus|||Perikaryon|||Perinatal mortality associated with severe disruption of the cytoarchitecture of the brain cortex as a result of defects in neuronal migration and cohesiveness, and degenerative changes in large neurons of the brain stem, such as motor neurons in the lower cranial nerve nuclei and spinal cord. Disruption of lamination in the cerebral cortex, hippocampus, and cerebellum. Hypomyelination caused by impaired differentiation of oligodendrocytes.|||Phosphorylation at Ser-159 is essential for maximal catalytic activity.|||Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by casein kinase 1 promotes kinase activity. By contrast, phosphorylation at Thr-14 inhibits activity (By similarity).|||Postsynaptic density|||Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Negatively regulates the CACNA1B/CAV2.2 -mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in postmitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-BMAL1 heterodimer in association with altered stability and subcellular distribution.|||Specifically expressed in postmitotic neurons and postsynaptic muscle.|||Synapse|||growth cone|||lamellipodium http://togogenome.org/gene/10090:Cd300lf ^@ http://purl.uniprot.org/uniprot/Q6SJQ7 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Acts as a functional murine norovirus (MNV) receptor that mediates binding to the cell surface and is both necessary and sufficient for viral entry and replication. Primary determinant of MNV species tropism and is sufficient to render cells permissive to infection by MNV. Can render nonmurine mammalian cells susceptible to MNV infection (PubMed:27681626, PubMed:27540007).|||Acts as an inhibitory receptor for myeloid cells and mast cells (PubMed:17438331). Positively regulates the phagocytosis of apoptotic cells (efferocytosis) via phosphatidylserine (PS) recognition; recognizes and binds PS as a ligand which is expressed on the surface of apoptotic cells (PubMed:21865548). Plays an important role in the maintenance of immune homeostasis, by promoting macrophage-mediated efferocytosis and by inhibiting dendritic cell-mediated efferocytosis (PubMed:26768664). Negatively regulates Fc epsilon receptor-dependent mast cell activation and allergic responses via binding to ceramide which acts as a ligand (PubMed:23123064). May act as a coreceptor for interleukin 4 (IL-4). Associates with and regulates IL-4 receptor alpha-mediated responses by augmenting IL-4- and IL-13-induced signaling (PubMed:26124135). Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 and TRIF through activation of PTPN6/SHP-1 and PTPN11/SHP-2 (By similarity). Inhibits osteoclast formation (PubMed:14662855). Induces macrophage cell death upon engagement (PubMed:18097021).|||Belongs to the CD300 family.|||Cell membrane|||Expressed in myeloid cells. Present on the surface of macrophages (at protein level). Highly expressed by alveolar, splenic macrophages and bone marrow-derived dendritic cells. Expression is increased following aeroallergen challenge in macrophages, mast cells, and eosinophils.|||Interacts with PTPN6/SHP-1 in a tyrosine phosphorylation dependent manner (PubMed:14662855). Interacts with IL4R (PubMed:26124135).|||Phosphorylated on tyrosine.|||Up-regulated by interleukin-4/IL-4. http://togogenome.org/gene/10090:Mettl4 ^@ http://purl.uniprot.org/uniprot/Q3U034 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MT-A70-like family.|||Embryonic sublethality and craniofacial dysmorphism (PubMed:30982744). Surviving mice display anatomical defects, including anophthalmia and craniofacial dysmorphism (PubMed:30982744). Adult mice are moribund and exhibited splenomegaly with anemia and severe leukopenia, indicative of aberrant hematopoiesis (PubMed:30982744).|||N(6)-adenine-specific methyltransferase that can methylate both RNAs and DNA (PubMed:30982744). Acts as a N(6)-adenine-specific RNA methyltransferase by catalyzing formation of N6,2'-O-dimethyladenosine (m6A(m)) on internal positions of U2 small nuclear RNA (snRNA): methylates the 6th position of adenine residues with a pre-deposited 2'-O-methylation (By similarity). Internal m6A(m) methylation of snRNAs regulates RNA splicing (By similarity). Also able to act as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine) (PubMed:30982744). The existence of N(6)-methyladenosine (m6A) on DNA is however unclear in mammals, and additional evidences are required to confirm the role of the N(6)-adenine-specific DNA methyltransferase activity of METTL4 in vivo (By similarity). Acts as a regulator of mitochondrial transcript levels and mitochondrial DNA (mtDNA) copy number by mediating mtDNA N(6)-methylation: m6A on mtDNA reduces transcription by repressing TFAM DNA-binding and bending (By similarity). N(6)-methyladenosine deposition by METTL4 regulates Polycomb silencing by triggering ubiquitination and degradation of sensor proteins ASXL1 and MPND, leading to inactivation of the PR-DUB complex and subsequent preservation of Polycomb silencing (PubMed:30982744).|||Nucleus|||The existence of N(6)-methyladenosine on DNA is unclear in mammals (By similarity). According to a report, the majority of N(6)-methyladenosine in DNA originates from RNA catabolism via a nucleotide salvage pathway and is misincorporated by DNA polymerases, arguing against a role as epigenetic DNA mark in mammalian cells (By similarity). Additional evidences are therefore required to confirm the role of METTL4 as a N(6)-adenine-specific DNA methyltransferase in vivo (By similarity). http://togogenome.org/gene/10090:Tafa1 ^@ http://purl.uniprot.org/uniprot/Q7TPG8 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TAFA family.|||Detected as early as 12.5 dpc, expression peaks between postnatal day 1 and day 7 and decreases at week 8 after birth (at protein level).|||Expressed in the hippocampus and detected also in the cortex (at protein level).|||Expression decreases upon brain injury.|||Regulatory factor which is ligand for CMKLR2 and is involved in the modulation of neural stem-cell proliferation and differentiation.|||Secreted http://togogenome.org/gene/10090:Slc2a3 ^@ http://purl.uniprot.org/uniprot/P32037|||http://purl.uniprot.org/uniprot/Q3TPL8|||http://purl.uniprot.org/uniprot/Q8BLF7 ^@ Activity Regulation|||Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Cell membrane|||Cell projection|||Deoxyglucose transport is inhibit by D-glucose, D-galactose and maltose. Galactose transport is inhibited by D-glucose and maltose.|||Detected in brain (at protein level). Highly expressed in brain.|||Facilitative glucose transporter (PubMed:35810171). Can also mediate the uptake of various other monosaccharides across the cell membrane (By similarity). Mediates the uptake of glucose, 2-deoxyglucose, galactose, mannose, xylose and fucose, and probably also dehydroascorbate (By similarity). Does not mediate fructose transport (By similarity). Required for mesendoderm differentiation (PubMed:35810171).|||Facilitative glucose transporter that can also mediate the uptake of various other monosaccharides across the cell membrane. Mediates the uptake of glucose, 2-deoxyglucose, galactose, mannose, xylose and fucose, and probably also dehydroascorbate. Does not mediate fructose transport.|||Interacts with SMIM43; the interaction may promote SLC2A3-mediated glucose transport to meet the energy needs of mesendoderm differentiation.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Perikaryon|||Transport is mediated via a series of conformation changes, switching between a conformation where the substrate-binding cavity is accessible from the outside, and a another conformation where it is accessible from the cytoplasm. http://togogenome.org/gene/10090:Dclre1b ^@ http://purl.uniprot.org/uniprot/Q8C7W7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways. Together with TERF2, required to protect telomeres from replicative damage during replication by controlling the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Also involved in response to DNA damage: plays a role in response to DNA interstrand cross-links (ICLs) by facilitating double-strand break formation. In case of spindle stress, involved in prophase checkpoint. Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin (By similarity). Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (By similarity).|||Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.|||Embryos are smaller than wild-type embryos and neonates die during the first day after birth. Cells activate the ATM kinase at their telomeres in S phase and show leading-end telomere fusions which are accompanied by a reduction in the telomeric overhang signal.|||Interacts with MUS81, MRE11 and FANCD2. Interacts with HSPA2, HSPA8 and HSPA14. Interacts with SPAG5 (By similarity). Interacts with TERF2; the interaction is direct.|||Nucleus|||The TBM domain mediates interaction with TERF2.|||Ubiquitinated, leading to its degradation. Interaction with TERF2 protects it from ubiquitination (By similarity).|||centrosome|||telomere http://togogenome.org/gene/10090:Ctag2l2 ^@ http://purl.uniprot.org/uniprot/A2BG94 ^@ Similarity ^@ Belongs to the CTAG/PCC1 family. http://togogenome.org/gene/10090:Pip4p1 ^@ http://purl.uniprot.org/uniprot/E0CZ18|||http://purl.uniprot.org/uniprot/E0CZF6|||http://purl.uniprot.org/uniprot/F8WHW3|||http://purl.uniprot.org/uniprot/Q3TWL2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P) (By similarity). Does not hydrolyze phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-bisphosphate, inositol 3,5-bisphosphate, inositol 3,4-bisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate (By similarity). Regulates lysosomal positioning by recruiting JIP4 to lysosomal membranes, thus inducing retrograde transport of lysosomes along microtubules (By similarity). Contributes to assembly of the V-ATPase complex in lipid rafts of the lysosomal membrane and to subsequent amino acid-dependent activation of mTORC1 (PubMed:29644770). May play a role in the regulation of cellular cholesterol metabolism (By similarity).|||Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P).|||Cell membrane|||Endosome membrane|||Interacts (via transmembrane domain) with ATP6V0D1 (PubMed:29644770). Interacts with LAMTOR1, RRAGA and RRAGC (PubMed:29644770).|||Late endosome membrane|||Lysosome membrane|||Membrane|||phagosome membrane http://togogenome.org/gene/10090:Or52e18 ^@ http://purl.uniprot.org/uniprot/Q7TRP3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nlrx1 ^@ http://purl.uniprot.org/uniprot/Q3TL44 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NLRP family.|||Expressed in macrophages (at protein level).|||Females infected with L.guyanensis containing dsRNA LRV1 virus, have an increase in footpad swelling and, in thickness and in immune cell infiltration in the dermis (PubMed:35651602). They develop larger lesions (PubMed:35651602). Ifnb and Il6, but not Tnfa, mRNA levels are also increased (PubMed:35651602). Parasite burden is similar to infected wild type female (PubMed:35651602). In contrast, males infected with L.guyanensis containing dsRNA LRV1 virus have similar lesions compared to infected wild type male (PubMed:35651602). However, Ifnb mRNA levels in the lesions and parasite burden are reduced (PubMed:35651602).|||Homohexamer (By similarity). Interacts with MAVS (By similarity). Interacts with TUFM (By similarity).|||In macrophages, transiently down-regulated in response to TLR3 ligands and to L.guyanensis containing dsRNA LRV1 virus infection; however, protein levels are not affected.|||Mitochondrion outer membrane|||Participates in antiviral signaling (PubMed:35651602). Acts as a negative regulator of MAVS-mediated antiviral responses, through the inhibition of the virus-induced RLH (RIG-like helicase)-MAVS interaction (By similarity). Instead, promotes autophagy by interacting with TUFM and subsequently recruiting the autophagy-related proteins ATG5 and ATG12 (By similarity). Regulates also MAVS-dependent NLRP3 inflammasome activation to attenuate apoptosis (By similarity). Has no inhibitory function on NF-kappa-B signaling pathway, but enhances NF-kappa-B and JUN N-terminal kinase dependent signaling through the production of reactive oxygen species (By similarity). Regulates viral mediated-inflammation and energy metabolism in a sex-dependent manner (PubMed:35651602). In females, prevents uncontrolled inflammation and energy metabolism and thus, may contribute to the sex differences observed in infectious and inflammatory diseases (PubMed:35651602).|||The LRRCT domain mediates homodimerization and LRRNT mediates trimerization of the dimers. http://togogenome.org/gene/10090:Slc6a11 ^@ http://purl.uniprot.org/uniprot/P31650 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A11 subfamily.|||Brain.|||Cell membrane|||GABA transport is inhibited by beta-alanine, taurine, hypotaurine, beta-guanidinopropionic acid and 2,3-diaminopropionic acid (PubMed:8420981). Beta-alanine transport is inhibited by GABA (PubMed:8420981).|||Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:8420981, PubMed:30270321). Can also mediate transport of beta-alanine and to a lower extent that of taurine and hypotaurine (PubMed:8420981, PubMed:30270321). http://togogenome.org/gene/10090:Fcamr ^@ http://purl.uniprot.org/uniprot/Q2TB54 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in several tissues including thymus, spleen, liver, kidney, small and large intestine, testis and placenta. Expressed by oligodendrocytes, B-cells and macrophages but not granulocytes, T-cells or NK cells (at protein level).|||Functions as a receptor for the Fc fragment of IgA and IgM. Binds IgA and IgM with high affinity and mediates their endocytosis. May function in the immune response to microbes mediated by IgA and IgM.|||N-glycosylated. http://togogenome.org/gene/10090:Slamf1 ^@ http://purl.uniprot.org/uniprot/Q9QUM4 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Involved in innate immune response against Gram-negative bacteria in macrophages; probably recognizes OmpC and/or OmpF on the bacterial surface, regulates phagosome maturation and recruitment of the PI3K complex II (PI3KC3-C2) leading to accumulated of PdtIns(3)P and NOX2 activity in the phagosomes (PubMed:20818396, PubMed:22493499).|||Cell membrane|||Interacts (via cytoplasmic domain) with SH2D1A and SH2D1B; SH2D1A mediates association with FYN; SH2D1A binds to phosphorylated and not phosphorylated ITSM 1 (PubMed:9774102, PubMed:16847311, PubMed:11477403). Interacts (via cytoplasmic domain phosphorylated on tyrosine residues) with INPP5D and PTPN11; presence of SH2D1A facilitates binding to INPP5D (By similarity). Interacts with MAP4K1 (By similarity). Interacts with PIK3C3, BECN1 and UVRAG; indicative for an association with PI3K complex II (PI3KC3-C2) (PubMed:22493499).|||Phosphorylated on tyrosine residues by FYN (By similarity).|||Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. SLAMF1-induced signal-transduction events in T-lymphocytes are different from those in B-cells. Two modes of SLAMF1 signaling seem to exist: one depending on SH2D1A (and perhaps SH2D1B) and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction operates. Initially it has been proposed that association with SH2D1A prevents binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2 (By similarity). However, signaling is also regulated by SH2D1A which can simultaneously interact with and recruit FYN which subsequently phosphorylates and activates SLAMF1 (By similarity). Mediates IL-2-independent proliferation of activated T-cells during immune responses and induces IFN-gamma production (PubMed:9126961, PubMed:12351401). Downstreaming signaling involves INPP5D, DOK1 and DOK2 leading to inhibited IFN-gamma production in T-cells, and PRKCQ, BCL10 and NFKB1 leading to increased T-cell activation and Th2 cytokine production (PubMed:11477403, PubMed:16847311, PubMed:15539155). Promotes T-cell receptor-induced IL-4 secretion by CD4(+) cells (PubMed:15123745). Inhibits antigen receptor-mediated production of IFN-gamma, but not IL-2, in CD4(-)/CD8(-) T-cells (PubMed:11477403). Required for IL-4 production by germinal centers T follicular helper (T(Fh))cells (PubMed:20525889). May inhibit CD40-induced signal transduction in monocyte-derived dendritic cells (By similarity). May play a role in allergic responses and may regulate allergen-induced Th2 cytokine and Th1 cytokine secretion (PubMed:16528012). In conjunction with SLAMF6 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (PubMed:18031695). Involved in the peripheral differentiation of indifferent natural killer T (iNKT) cells toward a regulatory NKT2 type (PubMed:18606638). In macrophages involved in down-regulation of IL-12, TNF-alpha and nitric oxide in response to lipopolysaccharide (LPS) (PubMed:15123745). In B-cells activates the ERK signaling pathway independently of SH2D1A but implicating both, SYK and INPP5D, and activates Akt signaling dependent on SYK and SH2D1A (PubMed:15315965). In conjunction with CD84/SLAMF5 and SLAMF6 may be a negative regulator of the humoral immune response (PubMed:25926831).|||The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. For SLAMF1 a 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). Binding is mediated by either three 'prongs' (for high affinity binding involving ITSM 1) or a combination of any two also including non-phosphorylated Tyr-288 of ITSM 1 thus providing a positive feedback loop implicating SH2D1A-dependent recruitment of activating FYN. ITSM 2 needs to be phosphorylated on Tyr-335 for SH2D1A binding. http://togogenome.org/gene/10090:Celf4 ^@ http://purl.uniprot.org/uniprot/Q7TSY6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CELF/BRUNOL family.|||Cytoplasm|||Expressed in muscle and brain at 14 dpc (at protein level). Expressed in embryo at 7.5 dpc.|||Expressed strongly in skeletal muscle, heart and adipose tissue (at protein level). Expressed in the brain and cerebellum.|||Nucleus|||RNA-binding protein implicated in the regulation of pre-mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Promotes exclusion of both the smooth muscle (SM) and non-muscle (NM) exons in actinin pre-mRNAs. Activates the splicing of MAPT/Tau exon 10. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA (By similarity). http://togogenome.org/gene/10090:Psmb10 ^@ http://purl.uniprot.org/uniprot/O35955 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.|||Belongs to the peptidase T1B family.|||Cytoplasm|||Detected in liver (at protein level).|||Impaired response of cytotoxic T-lymphocyte (CTL) to dominant epitopes of lymphocytic choriomeningitis virus (LCMV).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB7. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.|||The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Plays a role in determining the T-cell repertoire for an antiviral T-cell response.|||Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. http://togogenome.org/gene/10090:Or8b1c ^@ http://purl.uniprot.org/uniprot/L7N1X5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Otud3 ^@ http://purl.uniprot.org/uniprot/B1AZ99 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation ^@ Cytoplasm|||Deubiquitinating enzyme that hydrolyzes 'Lys-6'- and 'Lys-11'-linked polyubiquitin (PubMed:35675826). Also hydrolyzes heterotypic (mixed and branched) and homotypic chains (PubMed:35675826). Important regulator of energy metabolism (PubMed:35675826). Glucose and fatty acids trigger its nuclear translocation by CBP-dependent acetylation (PubMed:35675826). In the nucleus, deubiquitinates and stabilizes the nuclear receptor PPARD regulating the expression of various genes involved in glucose and lipid metabolism and oxidative phosphorylation (PubMed:35675826). Also acts as a negative regulator of the ribosome quality control (RQC) by mediating deubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS20/uS10, thereby antagonizing ZNF598-mediated 40S ubiquitination (By similarity).|||Glucose and fatty acids stimulate CREBBP-dependent acetylation, promoting its nuclear translocation.|||Knockout mice develope worse obesity, dyslipidemia and insulin resistance than wild-type mice when challenged with a high-fat diet.|||Nucleus|||Specificity is given by the S1' ubiquitin-binding site within the OTU domain composed of the Cys-, His- and Variable-loops.|||The UBA-like domain has no influence on ubiquitin hydrolysis. http://togogenome.org/gene/10090:Pmpca ^@ http://purl.uniprot.org/uniprot/Q9DC61 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M16 family.|||Does not seem to have protease activity as it lacks the zinc-binding site.|||Heterodimer of PMPCA (alpha) and PMPCB (beta) subunits, forming the mitochondrial processing protease (MPP) in which PMPCA is involved in substrate recognition and binding and PMPCB is the catalytic subunit.|||Mitochondrion inner membrane|||Mitochondrion matrix|||Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins. http://togogenome.org/gene/10090:Rmc1 ^@ http://purl.uniprot.org/uniprot/Q8VC42 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RMC1 family.|||Componement of the CCZ1-MON1 RAB7A guanine exchange factor (GEF). Acts as a positive regulator of CCZ1-MON1A/B function necessary for endosomal/autophagic flux and efficient RAB7A localization.|||Found in a complex with RMC1, CCZ1, MON1A and MON1B.|||Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Late endosome membrane|||Lysosome membrane http://togogenome.org/gene/10090:Rad54b ^@ http://purl.uniprot.org/uniprot/Q6PFE3|||http://purl.uniprot.org/uniprot/Q8BKE5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Interacts with APBA1 (via PDZ 1 and 2 domains).|||Interacts with RAD51 through the NH2-terminal domain.|||Involved in DNA repair and mitotic recombination. May play an active role in recombination processes in concert with other members of the RAD52 epistasis group.|||Nucleus|||Transcriptional repressor that down-regulates the expression of the fibrinogen gamma chain. Represses transcription of GSK3B gene promoter via its interaction with APBA1. http://togogenome.org/gene/10090:Oas2 ^@ http://purl.uniprot.org/uniprot/E9Q9A9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 2-5A synthase family.|||Cytoplasm|||Expressed in the uterus (PubMed:12396720). Expressed in mammary glands: expressed at low level before the establishment of lactation, then expression strongly increases, and subsequently decreases during early involution (PubMed:29117179).|||Glycosylated. Glycosylation is essential for its activity.|||Homodimer.|||Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:12396720, PubMed:29117179). Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation (PubMed:29117179). Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:21142819). Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL (PubMed:21142819). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation (PubMed:21142819). May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates (PubMed:29117179). Non-infected lobules would not be affected, allowing efficient pup feeding during infection (PubMed:29117179).|||Myristoylation is not essential for its activity.|||Produced as a latent enzyme which is activated by double stranded RNA (dsRNA) generated during the course of viral infection (PubMed:29117179). The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (By similarity). ssRNA or dsDNA do not act as activators (By similarity). Strongly inhibited by copper, iron and zinc ions (By similarity). Partially inhibited by cobalt and nickel ions (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Peli2 ^@ http://purl.uniprot.org/uniprot/E9QPQ6|||http://purl.uniprot.org/uniprot/Q8BST6 ^@ Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the pellino family.|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates IL1B-induced IRAK1 'Lys-63'-linked polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be important for LPS- and IL1B-induced MAP3K7-dependent, but not MAP3K3-dependent, NF-kappa-B activation. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1.|||Interacts with TRAF6, IRAK4 and MAP3K7 (By similarity). Interacts with IRAK1. Interacts with BCL10; this interaction is impaired by SOCS3.|||Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase activity.|||The atypical FHA domain contains a 'wing' insert and mediates binding to threonine-phosphorylated IRAK1.|||Widely expressed both in embryos and adult. Weakly or not expressed in spleen and thymus. http://togogenome.org/gene/10090:Eif3j1 ^@ http://purl.uniprot.org/uniprot/Q3UGC7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit J family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. This subunit binds directly within the mRNA entry channel of the 40S ribosome to the aminoacyl (A) site. It may regulate the interaction between the 43S PIC and mRNA.|||Cytoplasm|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation. http://togogenome.org/gene/10090:Zscan4f ^@ http://purl.uniprot.org/uniprot/Q3URS2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Transcription factor required to regulate early development. Binds telomeres and plays a key role in genomic stability by regulating telomere elongation. Acts as an activator of spontaneous telomere sister chromatid exchange (T-SCE) and telomere elongation (By similarity).|||Up-regulated in blastocyst outgrowths and is detectable in a mosaic fashion in ES cultures.|||telomere http://togogenome.org/gene/10090:Foxd4 ^@ http://purl.uniprot.org/uniprot/Q60688 ^@ Developmental Stage|||Domain|||Subcellular Location Annotation|||Tissue Specificity ^@ Contains two potential transactivation domains A and B.|||Expressed in headfold stage embryos in the notochord, the anterior neuroectoderm, and a few cells of the definite endoderm. This expression becomes restricted to the anteriormost portions of the invaginating foregut and the developing midbrain. From day 11.5 of gestation onward, FOXD4 transcripts are restricted to the midbrain and become progressively localized to the red nuclei as the sole site of expression.|||Not detected in any adult tissues tested.|||Nucleus http://togogenome.org/gene/10090:Arhgap22 ^@ http://purl.uniprot.org/uniprot/Q8BL80 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with VEZF1.|||Nucleus|||Predominantly present in endothelial cells (at protein level).|||Rho GTPase-activating protein involved in the signal transduction pathway that regulates endothelial cell capillary tube formation during angiogenesis. Acts as a GTPase activator for the RAC1 by converting it to an inactive GDP-bound state. Inhibits RAC1-dependent lamellipodia formation. May also play a role in transcription regulation via its interaction with VEZF1, by regulating activity of the endothelin-1 (EDN1) promoter. http://togogenome.org/gene/10090:Tbx22 ^@ http://purl.uniprot.org/uniprot/E9Q5R8|||http://purl.uniprot.org/uniprot/Q8BKE4|||http://purl.uniprot.org/uniprot/Q8K402 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation ^@ Expressed in a temporally and spatially highly restricted pattern during mouse palate and tongue development.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Probable transcriptional regulator involved in developmental processes. This is major determinant crucial to palatogenesis. http://togogenome.org/gene/10090:Vmn1r210 ^@ http://purl.uniprot.org/uniprot/Q8R274 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Ctnna1 ^@ http://purl.uniprot.org/uniprot/P26231|||http://purl.uniprot.org/uniprot/Q545R0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:21145499). May play a crucial role in cell differentiation.|||Belongs to the vinculin/alpha-catenin family.|||Cell junction|||Cell membrane|||Expressed ubiquitously in normal tissues.|||Membrane|||Monomer and homodimer; the monomer preferentially binds to CTNNB1 and the homodimer to actin (PubMed:16325583). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (By similarity). Possible component of an E-cadherin/ catenin adhesion complex together with E-cadherin/CDH1 and beta-catenin/CTNNB1 or gamma-catenin/JUP; the complex is located to adherens junctions (PubMed:7982500, PubMed:16325582, PubMed:16325583, PubMed:18093941, PubMed:25653389, PubMed:10882138). The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex (PubMed:16325582, PubMed:18093941). Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1 (PubMed:18093941). Binds AFDN and F-actin (PubMed:11907041). Interacts with LIMA1 (By similarity) (PubMed:18093941). Interacts with ARHGAP21 (By similarity). Interacts with AJUBA (By similarity). Interacts with vinculin/VCL (By similarity). Interacts with TJP2/ZO2 (via N-terminus) (PubMed:10026224). Interacts with TJP1/ZO1 (via N-terminus) (PubMed:10026224).|||Phosphorylation seems to contribute to the strength of cell-cell adhesion rather than to the basic capacity for cell-cell adhesion.|||Sumoylated.|||adherens junction|||cytoskeleton http://togogenome.org/gene/10090:Mplkip ^@ http://purl.uniprot.org/uniprot/Q9D011 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with PLK1; phosphorylation-dependent.|||May play a role in maintenance of cell cycle integrity by regulating mitosis or cytokinesis.|||Nucleus|||Phosphorylated during mitosis in the cell cycle probably by CDK1.|||centrosome http://togogenome.org/gene/10090:Tspan9 ^@ http://purl.uniprot.org/uniprot/Q8BJU2 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Found in a complex with GP6.|||Glycosylated.|||Membrane|||Strongly expressed in megakaryocytes, platelets and lung. Weakly expressed in bone marrow, brain and kidney (at protein level). http://togogenome.org/gene/10090:Dlx3 ^@ http://purl.uniprot.org/uniprot/Q64205|||http://purl.uniprot.org/uniprot/Q78ZZ8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the distal-less homeobox family.|||Cytoplasm|||Heterodimer with MEIS1 (By similarity). Interacts with IPO7; the interaction facilitates nuclear translocation of DLX3 in dental papilla cells (PubMed:35922041).|||Not expressed in the central nervous system at 16.5 dpc (PubMed:7893603). Initially expressed in the branchial arches at 9.5 dpc, expression is confined to the caudal portion of the mandibular process at 10.5 dpc (PubMed:7893603). Distally expressed in the posterior regions of the first and second branchial arches at 10.5 dpc (PubMed:7893603). Expressed in the auditory hillocks, ventral olfactory bulbs, the oral epithelium and the external naris at 12.5 dpc (PubMed:7893603). Expressed in the area under the first branchial cleft from which the external ear develops, in cell adjacent to Meckel's cartilage, in the external naris and mesenchymal cells that enclose the nasal epithelium at 13.5 dpc (PubMed:7893603). Expressed in the developing otic vesicle at 11.5 dpc, expression is then restricted to the vestibular region at 12.5 dpc and further restricted to the epithelium of the utricle and the semicircular canals at 13.5 dpc (PubMed:7893603). Expression declines thereafter with no expression detected in the developing inner ear at 14.5 dpc (PubMed:7893603). Expressed in the mesenchyme of the dental papilla at 13.5 dpc, expression remains in ameloblasts and odontoblasts at 16.5 dpc (PubMed:7893603). Expressed in a patchy pattern in the epithelium of the upper lip at 12.5 dpc, expression is increased in follicles during whisker development from 14.5 dpc until birth (PubMed:7893603).|||Nucleus|||Transcriptional activator (PubMed:23371388). Activates transcription of GNRHR, via binding to the downstream activin regulatory element (DARE) in the gene promoter (PubMed:23371388). http://togogenome.org/gene/10090:Ctns ^@ http://purl.uniprot.org/uniprot/P57757|||http://purl.uniprot.org/uniprot/Q542U5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cystinosin family.|||Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:12370309). Plays an important role in melanin synthesis by catalyzing cystine export from melanosomes, possibly by inhibiting pheomelanin synthesis (PubMed:22649030). In addition to cystine export, also acts as a positive regulator of mTORC1 signaling in kidney proximal tubular cells, via interactions with components of the v-ATPase and Ragulator complexes (PubMed:26449607). Also involved in small GTPase-regulated vesicle trafficking and lysosomal localization of LAMP2A, independently of cystine transporter activity (PubMed:28465352).|||Interacts with components of the V-ATPase complex (PubMed:26449607). Interacts with components of the Ragulator complex (PubMed:26449607). Interacts with RRAGA/RagA and RRAGC/RagC (PubMed:26449607). Interacts with AP-3 complex subunit mu (AP3M1 or AP3M2) (By similarity).|||Lysosome membrane|||Melanosome membrane|||Membrane|||Mice develop ocular damages, bone defects and behavioral anomalies (PubMed:12370309). Defects are caused by cystine accumulation in all organs tested, and formation of cystine crystals (PubMed:12370309). Mice do not develop signs of a proximal tubulopathy or renal failure (PubMed:12370309). Cystine accumulation in the central nervous system causes severe age-related memory deficits: spatial reference and working memory deficits are observed in middle-aged mice (PubMed:17977621). In eyes, cystine crystals induce inflammatory and immune response with aging associated with loss of keratocyte and endothelial cells (PubMed:21897743). Mice show a strong increase in hair pheomelanin content (PubMed:22649030). Decreased mTORC1 signaling pathway in proximal tubular cell lines (PubMed:26449607).|||The lysosomal targeting motif, together with te second PQ-loop mediate targeting to the lysosome. http://togogenome.org/gene/10090:Emc3 ^@ http://purl.uniprot.org/uniprot/Q99KI3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC3 family.|||Component of the ER membrane protein complex (EMC).|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Wasf1 ^@ http://purl.uniprot.org/uniprot/Q8R5H6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCAR/WAVE family.|||Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain.|||Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Interacts with SHANK3; the interaction mediates the association of SHANK3 with the WAVE1 complex. Interacts with ABI1 (via N-terminus). Interacts with SORBS2; this interaction greatly enhances phosphorylation by ABL1 and dephosphorylation by PTPN12 and might mediate partial to focal adhesion sites (By similarity).|||Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (PubMed:27605705). Also involved in the regulation of mitochondrial dynamics (By similarity).|||Highly expressed in brain.|||Synapse|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Plxna3 ^@ http://purl.uniprot.org/uniprot/A0A158SIT4|||http://purl.uniprot.org/uniprot/P70208 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.|||Detected in embryonic hindbrain, spinal cord, dorsal root ganglion, trigeminal ganglion and superior cervical ganglion. In newborns, detected throughout all layers of the hippocampus.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||No visible phenotype, but causes subtle changes in the central nervous system. Mice exhibit altered apical dendrite spine morphology in pyramidal neurons. Mice exhibit defasciculation of the facial branchiomotor nerve and of the ophthalmic branch of the trigeminus, with variable severity. The number of neurons in the dorsal root ganglion is higher than normal, probably due to reduced neuronal apoptosis. In mice lacking both Plxna3 and Plxna4, migrating neurons do not show the normal response to Sema3A and Sema3F and do not migrate away from these semaphorins (in vitro). http://togogenome.org/gene/10090:Psmb8 ^@ http://purl.uniprot.org/uniprot/P28063 ^@ Function|||Induction|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.|||Belongs to the peptidase T1B family.|||Cytoplasm|||Detected in liver (at protein level). Expressed in spleen, thymus, lung, liver, heart and, at a very low level, in kidney. Not expressed in brain nor testis.|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with TAP1.|||The allele, LMP7k/LMP7s/LMPf/LMP7r/LMPcas4/LMPg7 found in strains NMRI, B10.BR, SJL, A.CA, B10.RIII, B10.cas4 and NOD may be post-translationally modified. Allele LMP7q is found in strain DBA/1J.|||The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. May participate in the inflammatory response pathway. Required for adipocyte differentiation (PubMed:21881205, PubMed:22341445, PubMed:8066463). May be involved in the generation of spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (By similarity).|||Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Down-regulated in spleen by deoxynivalenol (DON), a mycotoxin that alters immune functions. Down-regulated by the selective inhibitor PR-957. Up-regulated by heat shock treatment. Down-regulated by EGR1 in neuronal cells. http://togogenome.org/gene/10090:Tff1 ^@ http://purl.uniprot.org/uniprot/Q08423 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Secreted|||Stabilizer of the mucous gel overlying the gastrointestinal mucosa that provides a physical barrier against various noxious agents.|||Strong expression found in normal gastric mucosa. Not detected in the small or large intestine nor in normal mammary gland. http://togogenome.org/gene/10090:Retnlb ^@ http://purl.uniprot.org/uniprot/A0A0R4J042|||http://purl.uniprot.org/uniprot/Q99P86 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the resistin/FIZZ family.|||Homodimer; disulfide-linked (PubMed:11358969, PubMed:15834545, PubMed:15155948). Heterodimer with RETNLG (PubMed:15834545).|||Probable hormone.|||Secreted|||Strongly expressed in colon, and at lower levels in ileum (PubMed:15834545). In colon, found throughout the crypt and surface epithelium and in goblet cells (at protein level) (PubMed:15834545). Specific to the gastrointestinal tract; not detected in other tissues tested (PubMed:11209052, PubMed:15834545).|||Up-regulated in colon in response to a high-fat diet. Also up-regulated in obese mice mutant for the leptin receptor LEPR (db/db genotype). http://togogenome.org/gene/10090:Stx12 ^@ http://purl.uniprot.org/uniprot/Q9ER00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the BLOC-1 complex. Interacts with BLOC1S6. Interacts with NAPA and SNAP23. Identified in a complex containing STX6, STX12, VAMP4 and VTI1A (By similarity). Interacts with GRIPAP1 (PubMed:20098723). Forms a complex with GRIP1, GRIA2 and NSG1; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). Interacts with NSG1 (PubMed:12070131). Interacts with TPC1 (PubMed:28855648). Interacts (via N-terminus) with VPS13B (By similarity).|||Belongs to the syntaxin family.|||Early endosome membrane|||Endomembrane system|||Endosome membrane|||Golgi apparatus membrane|||Recycling endosome membrane|||SNARE promoting fusion of transport vesicles with target membranes. Together with SNARE STX6, promotes movement of vesicles from endosomes to the cell membrane, and may therefore function in the endocytic recycling pathway. Through complex formation with GRIP1, GRIA2 and NSG1 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. http://togogenome.org/gene/10090:Misp ^@ http://purl.uniprot.org/uniprot/Q9D279 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with F-actin. Interacts with DCTN1; this interaction regulates DCTN1 distribution at the cell cortex. Interacts with PTK2/FAK and MAPRE1 (By similarity).|||Belongs to the MISP family.|||Phosphorylated by CDK1 and PLK1. CDK1 is the priming kinase for PLK1 phosphorylation. Phosphorylation by PLK1 is required for proper spindle orientation at metaphase (By similarity).|||Plays a role in mitotic spindle orientation and mitotic progression. Regulates the distribution of dynactin at the cell cortex in a PLK1-dependent manner, thus stabilizing cortical and astral microtubule attachments required for proper mitotic spindle positioning. May link microtubules to the actin cytoskeleton and focal adhesions. May be required for directed cell migration and centrosome orientation. May also be necessary for proper stacking of the Golgi apparatus (By similarity).|||cell cortex|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Dvl3 ^@ http://purl.uniprot.org/uniprot/E9Q967|||http://purl.uniprot.org/uniprot/Q61062 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine methylation may function as a switch in regulation of function in Wnt signaling.|||Belongs to the DSH family.|||Cytoplasm|||Interacts (via the PDZ domain) with the C-terminal regions of VANGL1 and VANGL2. Interacts (via the region containing both the PDZ and DEP domains) with LRRFIP2; the DIX domain may inhibit this interaction. Interacts with CYLD. Interacts with CEP164 and DAB2. Interacts with DCDC2. Interacts with FOXK1 and FOXK2 (By similarity). Interacts with DAAM2 (PubMed:22227309).|||Involved in the signal transduction pathway mediated by multiple Wnt genes.|||Phosphorylated by CSNK1D.|||Ubiquitinated. Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin chains (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Slc22a14 ^@ http://purl.uniprot.org/uniprot/Q497L9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Male mice show severe infertility (PubMed:27811987, PubMed:33882315). Defects are caused by impaired riboflavin transport that suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions (PubMed:33882315). In mutant spermatozoa, fatty acid beta-oxidation is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) and accumulation of triglycerides and free fatty acids (PubMed:33882315). Sperms display abnormal flagellar bending and impaired motility and capacitation (PubMed:27811987).|||Mitochondrion inner membrane|||Riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa midpiece, which is required for male fertility (PubMed:33882315). SLC22A14-mediated riboflavin transport is essential for spermatozoa energy generation and motility: riboflavin is the precursor of FMN and FAD, which are coenzymes of many enzymes in the TCA cycle (the citric acid cycle) in mitochondria (PubMed:33882315). Required for sperm motility and normal sperm flagellar structure (PubMed:27811987, PubMed:33882315).|||Testis-specific (at protein level) (PubMed:27811987). Specifically expressed in male germ cells (at protein level) (PubMed:27811987).|||flagellum membrane http://togogenome.org/gene/10090:Or6k2 ^@ http://purl.uniprot.org/uniprot/A6H6I2|||http://purl.uniprot.org/uniprot/E9Q4G0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Smcp ^@ http://purl.uniprot.org/uniprot/P15265 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||First detected in step 11 spermatids. Levels increase in subsequent steps to reach a maximum in late step 15 and early step 16. Levels decrease in late step 16.|||Involved in sperm motility. Its absence is associated with genetic background dependent male infertility. Infertility may be due to reduced sperm motility in the female reproductive tract and inability to penetrate the oocyte zona pellucida.|||Mitochondrion membrane|||Testis. Is selectively expressed in the spermatids of seminiferous tubules.|||Was originally (PubMed:2303168, PubMed:1418626) thought to be a selenoprotein and was known as sperm mitochondrial capsule selenoprotein. http://togogenome.org/gene/10090:Maoa ^@ http://purl.uniprot.org/uniprot/Q3TPD9|||http://purl.uniprot.org/uniprot/Q3UJ53|||http://purl.uniprot.org/uniprot/Q64133 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the flavin monoamine oxidase family.|||Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:7792602). Preferentially oxidizes serotonin (PubMed:7792602). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).|||Mitochondrion outer membrane|||Monomer, homo- or heterodimer (containing two subunits of similar size). Each subunit contains a covalently bound flavin. Enzymatically active as monomer (By similarity). http://togogenome.org/gene/10090:Blmh ^@ http://purl.uniprot.org/uniprot/Q8R016 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C1 family.|||Cytoplasm|||Cytoplasmic granule|||Homohexamer (By similarity). Interacts with NUDT12 (via ANK repeats) (By similarity).|||The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity. http://togogenome.org/gene/10090:Lbx2 ^@ http://purl.uniprot.org/uniprot/Q9WUN8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By PAX3 which regulates its expression.|||Expressed in the developing urogenital system, eye and brain.|||First detected at 10.5 dpc in the gonadal component of the urogenital ridge. Expression dramatically increases by 11.5 dpc in the urogenital ridges and in the cranial surface ectoderm. At this time, it is also expressed in the trigeminal ganglion and nodose ganglion. At later stages, it is expressed in the brain and organs derived from the urogenital ridge, including the gonadal tubercle, kidneys, and adrenal glands. From 14.5 dpc to birth, expression is evident in the developing retinal neuroepithelium and the vibrissa.|||Mice are healthy and fertile and do not display any abnormal phenotype.|||Nucleus|||Transcription factor. http://togogenome.org/gene/10090:Sgtb ^@ http://purl.uniprot.org/uniprot/Q8VD33 ^@ Function|||Similarity|||Subunit ^@ Belongs to the SGT family.|||Co-chaperone that binds directly to HSC70 and HSP70 and regulates their ATPase activity.|||Homooligomerize. http://togogenome.org/gene/10090:A4gnt ^@ http://purl.uniprot.org/uniprot/Q14BT6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 32 family.|||Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans. Necessary for the synthesis of type III mucin which is specifically produced in the stomach, duodenum, and pancreatic duct. May protect against inflammation-associated gastric adenocarcinoma.|||Golgi apparatus membrane|||The conserved DXD motif is involved in enzyme activity.|||Viable with no gross defects. Gastric mucosa cells and duodenal Brunner's glands have an altered O-linked glycosylation profile with complete loss of terminal alpha-1,4-linked N-acetylglucosamine residues (alpha-GlcNAc). Animals develop spontaneous gastric adenocarcinomas, with all individuals affected by 60 weeks of age. Hyperplasia of surface mucous cells and pyloric gland cells is observed as early as 5 weeks of age, associated with increased inflammatory responses in the gastric mucosa. http://togogenome.org/gene/10090:Nap1l5 ^@ http://purl.uniprot.org/uniprot/Q9JJF0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the nucleosome assembly protein (NAP) family.|||Nucleus http://togogenome.org/gene/10090:Cmklr1 ^@ http://purl.uniprot.org/uniprot/P97468|||http://purl.uniprot.org/uniprot/Q497D3 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the chemokine-like receptor (CMKLR) family.|||Cell membrane|||Down-regulated by bacterial lipopolysaccharide (LPS), IFN-alpha and TNF on macrophages.|||Expressed during bone development and in adult parathyroid glands. Expressed at 11 dpc in the caudal part of the tongue and the umbilical cord and the expression in the tongue was maintained throughout adulthood. Expression increases in bone and cartilaginous forming zones of embryo up to stage 14.5 dpc and at 16.5 dpc expression is seen in the lung.|||Expressed in the differentiated adipocytes (at protein level). Ubiquitous. Highly expressed in adipose tissue and immature plasmacytoid dendritic cells (DCs) and at lower levels in myeloid DCs, macrophages, and NK cells. Expressed on macrophages isolated from different tissues, including peritoneal cavities, pleural cavities and spleen.|||Membrane|||Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with RARRES2 initiates activation of G proteins G(i)/G(o) and beta-arrestin pathways inducing cellular responses via second messenger pathways such as intracellular calcium mobilization, phosphorylation of MAP kinases MAPK1/MAPK3 (ERK1/2), TYRO3, MAPK14/P38MAPK and PI3K leading to multifunctional effects, like, reduction of immune responses, enhancing of adipogenesis and angionesis. Resolvin E1 down-regulates cytokine production in macrophages by reducing the activation of MAPK1/3 (ERK1/2) and NF-kappa-B (By similarity). Positively regulates adipogenesis and adipocyte metabolism. http://togogenome.org/gene/10090:Rpl21 ^@ http://purl.uniprot.org/uniprot/O09167 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL21 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||Endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Rgs22 ^@ http://purl.uniprot.org/uniprot/G3UYX5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed testis, including in Leydig cells and spermatogenic cells from the spermatogonia to spermatid stages (at protein level).|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.|||Interacts with GNA11, GNA12 and GNA13.|||Nucleus http://togogenome.org/gene/10090:Serpina16 ^@ http://purl.uniprot.org/uniprot/D3Z660 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Mogat1 ^@ http://purl.uniprot.org/uniprot/Q91ZV4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the diacylglycerol acyltransferase family.|||Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. Probably not involved in absorption of dietary fat in the small intestine.|||Endoplasmic reticulum membrane|||Expressed at high level in kidney and stomach. Expressed at lower level in brown and white adipose tissue, uterus and liver. Not detected in small intestine. http://togogenome.org/gene/10090:Tmem65 ^@ http://purl.uniprot.org/uniprot/Q4VAE3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Low level expression seen in the heart between 8.5 dpc and 15.5 dpc. Expression levels increase progressively after birth, with the highest levels seen in adults.|||May play an important role in cardiac development and function. May regulate cardiac conduction and the function of the gap junction protein GJA1. May contribute to the stability and proper localization of GJA1 to cardiac intercalated disk thereby regulating gap junction communication (PubMed:26403541). Regulates mitochondrial respiration and mitochondrial DNA copy number maintenance (By similarity).|||Mitochondrion inner membrane|||Monomer. Homodimer. Interacts with GJA1. Interacts weakly with DSP.|||Predominantly expressed in the ventricular tissue (at protein level). http://togogenome.org/gene/10090:Slc7a6os ^@ http://purl.uniprot.org/uniprot/Q7TPE5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IWR1/SLC7A6OS family.|||Cytoplasm|||Directs RNA polymerase II nuclear import.|||Nucleus http://togogenome.org/gene/10090:Txn2 ^@ http://purl.uniprot.org/uniprot/P97493 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thioredoxin family.|||Important for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Possesses a dithiol-reducing activity.|||Mitochondrion http://togogenome.org/gene/10090:Tpd52 ^@ http://purl.uniprot.org/uniprot/E9PUA7|||http://purl.uniprot.org/uniprot/F8WHQ1|||http://purl.uniprot.org/uniprot/Q62393 ^@ Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TPD52 family.|||Forms a homodimer or heterodimer with other members of the family.|||Isoform 2 is expressed at higher levels in kidney and brain than in liver, lung, testis and heart. Within the brain, isoform 2 is highly expressed in the granular layer of the cerebellum, the cortex and the hippocampus. In embryos, isoform 2 is expressed in the epithelium of the developing intestine, stomach, olfactory epithelium, neuronal layers of the retina, salivary gland, kidney and dorsal root ganglion. http://togogenome.org/gene/10090:Fzd3 ^@ http://purl.uniprot.org/uniprot/Q61086 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Cell surface|||Expressed in the cortex, diencephalon, rostral brainstem and little or no staining is seen in the striatum or cerebellum. Expressed in both hair cells and supporting cells in the utricle, saccule, cristae and the organ of Corti in the inner ear (at protein level). Highly expressed in the CNS. In skin, it is restricted to the epidermis and to the developing hair follicle.|||Expressed throughout the developing central nervous system (CNS). Expressed in the cortex, diencephalon, and brainstem, with the most intense staining in the striatum and trigeminal ganglia at 18 dpc (at protein level). First detected in discrete foci in the developing epidermis of 13 days old embryos, later in the hair follicle placodes of 15 days old embryos. Expressed in the ventral and lateral margins of the spinal cord from 9.5 to 13.5 dpc, where post-crossing commissural axons project longitudinally. Expressed in superior sympathetic cervical ganglia (SCG) at 14.5 and 16.5 dpc, a stage when the SCG is comprised primarily of proliferating sympathetic neuroblasts. In 17 days embryos and 1 day old newborn, expression is limited to suprabasal keratinocytes and is not seen in pelage follicles until 3 days postpartum. In 7 days old neonatal skin, expression occurs throughout the epidermis and in the outer cell layers of hair follicles.|||Interacts with VANGL2.|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Neonate knockout mice have a curly tail, flexed lower limbs, breathe irregularly and typically die within 30 min of birth. Central nervous system (CNS) shows severe defects in the development of several major axon tracts, including: a nearly complete absence of the three early most prominent axon tracts in the brain and the ventral branch of the trigeminal nerve, absence of subcortical and striatal axons, the anterior commissure, misrouting of thalamocortical axons, a nearly complete absence of the corticospinal tract, the fasciculus retroflexus, and the mammillothalamic tract, poor fasciculation of the medial lemniscus and a disorganization of axon bundles in the reticular formation, severe defect in the asymmetric rostrocaudal orientation of dopaminergic and serotonergic axons, a large reduction or complete absence of ascending spinal axon tracts in the braistem, midbrain and thalamus, peripheral nerves defect in several motor neurons, such as in the VIIth and XIIth cranial motor nerves, the phrenic nerve, and the spinal motor nerve which failed to form connections with their respective targets and display also aberrant migration of a subpopulation of cranial neural crest cells (PubMed:12351730, PubMed:24347548, PubMed:24799694). Neonate knockout mice show fewer S-phase proliferating neuroblasts, premature cell cycle exit and enhanced apoptosis in early-stage superior cervical ganglia (SCGs), and in some cases, complete absence of sympathetic innervation of several peripheral targets (PubMed:21325504). Display also impaired rostral turning by growth cones of spinal cord commissural sensory axons (PubMed:14671310). FZD3 and FZD6 double knockout embryos have a curled tail, exhibit defects in neural tube and eyelids closure, in the orientation of hair bundles on inner-ear sensory cells and die at birth (PubMed:16495441). The following conditional knockout mice display the corresponding phenotypes: dopaminergic neuron-specific shows a defect in the orientation and growth of midbrain dopaminergic axons with an absence of striatum innervation; retinal ganglion cell (RGC)-specific displays a misrouting of a subset of optic tract axons and a lack of the medial terminal nucleus (MTN) innervation; neocortex neuron-specific displays a total absence of the posterior part of the anterior commissure and aberrant axon trajectories appearing in the external capsule; ventral telencephalon neuron-specific shows corticothalamic, thalamocortical and corticospinal tracts defect to various extent; telencephalon neuron-specific exhibits the full spectrum of axon defects seen in the classical null mutant knockout mice; cholinergic neuron-specific shows an absence of cholinergic fiber tracts passing through the striatum, a defective caudal migration of neurons of the VIIth motor nucleus and a loss of motor innervation to the face, a decrease in motor innervation of the tongue by the XIIth nerve and a complete loss of cholinergic neurons in the vomeronasal organ; oligodendrocyte neuron-specific leads to the complete spectrum of motor neuron phenotypes shown by the classical mutant knockout mice; caudal and upper thorax region-specific leads to a loss of motor innervation and an atrophy of anterior compartment muscles in the lower hindlimb by the deep peroneal nerve and a nearly absence in ascending spinal sensory axons in the brainstem, midbrain and thalamus altering the ability to transmit sensory information from the trunk and limbs to the brain in postnatal life (PubMed:24347548, PubMed:24799694).|||Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Plays a role in controlling early axon growth and guidance processes necessary for the formation of a subset of central and peripheral major fiber tracts. Required for the development of major fiber tracts in the central nervous system, including: the anterior commissure, the corpus callosum, the thalamocortical, corticothalamic and nigrostriatal tracts, the corticospinal tract, the fasciculus retroflexus, the mammillothalamic tract, the medial lemniscus, and ascending fiber tracts from the spinal cord to the brain. In the peripheral nervous system, controls axon growth in distinct populations of cranial and spinal motor neurons, including the facial branchimotor nerve, the hypoglossal nerve, the phrenic nerve, and motor nerves innervating dorsal limbs. Involved in the migration of cranial neural crest cells. May also be implicated in the transmission of sensory information from the trunk and limbs to the brain. Controls commissural sensory axons guidance after midline crossing along the anterior-posterior axis in the developing spinal cord in a Wnt-dependent signaling pathway. Together with FZD6, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle in a beta-catenin-dependent manner.|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Cgrrf1 ^@ http://purl.uniprot.org/uniprot/Q8BMJ7 ^@ Function|||Subcellular Location Annotation ^@ Able to inhibit growth in several cell lines.|||Endoplasmic reticulum|||Nucleus http://togogenome.org/gene/10090:Nicn1 ^@ http://purl.uniprot.org/uniprot/Q9CQM0 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in all tissues of the developing embryos.|||High expression level is found in brain, testis, liver and kidney. Weak expression in spleen, leukocytes, small intestin and colon.|||Nucleus|||Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1. http://togogenome.org/gene/10090:Olfr851 ^@ http://purl.uniprot.org/uniprot/Q7TRG0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ifit2 ^@ http://purl.uniprot.org/uniprot/Q64112 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IFIT family.|||By type I interferons, dsRNAs and viruses.|||Cytoplasm|||Domain-swapped homodimer. Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT1 and IFIT3. Interacts with STING1/MITA and disrupts its interaction with MAVS or TBK1 (By similarity). Interacts with EIF3C.|||Endoplasmic reticulum|||IFN-induced antiviral protein which inhibits expression of viral messenger RNAs lacking 2'-O-methylation of the 5' cap. The ribose 2'-O-methylation would provide a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Binds AU-rich viral RNAs, with or without 5' triphosphorylation, RNA-binding is required for antiviral activity. Can promote apoptosis.|||The C-terminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface. http://togogenome.org/gene/10090:Gmppa ^@ http://purl.uniprot.org/uniprot/Q922H4 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with GMPPB.|||Belongs to the transferase hexapeptide repeat family.|||Cytoplasm|||GMPPA is a close homolog of GMPPB, that has been shown to catalyze the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids. It has been hypothesized that GMPPA might serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose. Alignment of GMPPAs and GMPPBs from various species shows that GMPPAs are characterized by a 2 amino acid-insertion (residues 11-12) in a highly conserved motif that borders the catalytic pocket and binds the nucleotide substrate in homologous enzymes. This insertion might inactivate the ancestral catalytic site, converting it to an allosteric site (PubMed:24035193).|||May serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose.|||Widely expressed. http://togogenome.org/gene/10090:P2ry10 ^@ http://purl.uniprot.org/uniprot/Q8BFU7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Putative receptor for purines coupled to G-proteins. http://togogenome.org/gene/10090:Primpol ^@ http://purl.uniprot.org/uniprot/Q6P1E7 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic-type primase small subunit family.|||Can act both with Mn(2+) and Mg(2+) as cofactor in vitro, but Mn(2+) is the preferred cofactor in vivo. The polymerase activity incorporates correct dNTPs with much higher efficiency with Mn(2+) than with Mg(2+). The fidelity is slightly more accurate when Mg(2+) is the cofactor compared to Mn(2+). In the presence of Mn(2+), a conformational transition step from non-productive to productive PRIMPOL:DNA complexes limits the enzymatic turnover, whereas in the presence of Mg(2+), the chemical step becomes rate limiting.|||Chromosome|||DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (PubMed:26926109, PubMed:29073063). Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (By similarity). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (By similarity). Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (By similarity). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion (By similarity). Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (By similarity). Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (By similarity). Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (PubMed:29073063). Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis (PubMed:26926109). Has non-overlapping function with POLH (By similarity). In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (By similarity).|||Interacts with RPA1; leading to recruitment to chromatin and stimulate DNA primase activity. Interacts with SSBP1. Interacts with POLDIP2; leading to enhance DNA polymerase activity.|||Mice are viable but show defects in mitochondrial DNA synthesis.|||Mitochondrion matrix|||Nucleus|||The RPA1-binding motifs (RBM) mediate interaction with RPA1 and are essential for recruitment to chromatin. The interaction is primarily mediated by RPA1-binding motif 1, which binds to the basic cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding.|||The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-116 is required to stabilize the incoming nucleotide at the 3'-site.|||The zinc knuckle motif binds zinc and is required for the DNA primase activity. It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites. http://togogenome.org/gene/10090:Slc35c2 ^@ http://purl.uniprot.org/uniprot/Q5GMH2|||http://purl.uniprot.org/uniprot/Q8VCX2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPT transporter family. SLC35C subfamily.|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Higher expression at embryo stage 7.5 dpc than 11-17 dpc.|||May play an important role in the cellular response to tissue hypoxia. May be either a GDP-fucose transporter that competes with SLC35C1 for GDP-fucose, or a factor that otherwise enhances the fucosylation of Notch and is required for optimal Notch signaling in mammalian cells (By similarity).|||Membrane|||cis-Golgi network membrane http://togogenome.org/gene/10090:Srgap3 ^@ http://purl.uniprot.org/uniprot/Q812A2 ^@ Domain|||Function|||Sequence Caution|||Subunit ^@ GTPase-activating protein for RAC1 and perhaps CDC42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons (By similarity).|||Homodimer (Probable). Forms a heterooligomer with SRGAP1 and SRGAP2 through its F-BAR domain. Interacts with WASF1. Probably interacts with ROBO1. Interacts with FASLG (By similarity).|||Intron retention.|||Probable cloning artifact. Aberrant splice sites.|||The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions. http://togogenome.org/gene/10090:Cdc42ep3 ^@ http://purl.uniprot.org/uniprot/Q9CQC5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BORG/CEP family.|||Endomembrane system|||Interacts with RHOQ and CDC42, in a GTP-dependent manner, and with SEPT7.|||Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Gypa ^@ http://purl.uniprot.org/uniprot/P14220 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycophorin-A family.|||Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane. Glycophorin A is the major intrinsic membrane protein of the erythrocyte. The N-terminal glycosylated segment, which lies outside the erythrocyte membrane, has MN blood group receptors. Appears to be important for the function of SLC4A1 and is required for high activity of SLC4A1. May be involved in translocation of SLC4A1 to the plasma membrane. Is a receptor for influenza virus. Is a receptor for Plasmodium falciparum erythrocyte-binding antigen 175 (EBA-175); binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans. Appears to be a receptor for Hepatitis A virus (HAV).|||Homodimer. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with SLC4A1; a GYPA monomer is bound at each end of the SLC4A1 dimer forming an heterotetramer.|||Membrane|||The N-terminal extracellular domain is heavily glycosylated on serine and threonine residues.|||The amount of O-linked oligosaccharide chains in the erythrocyte membrane decreases to 60% compared to that of the wild-type mice. Erythrocytes lacking GPA are more sensitive to hypo-osmotic stress. http://togogenome.org/gene/10090:4930503L19Rik ^@ http://purl.uniprot.org/uniprot/Q8CB14 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Might play a role in cell proliferation.|||Secreted|||Widely expressed with highest levels in lung and spleen. Also expressed during embryonic development, at least from 7 to 17 dpc. http://togogenome.org/gene/10090:Tmem167b ^@ http://purl.uniprot.org/uniprot/Q80X45 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the KISH family.|||Golgi apparatus membrane|||Involved in the early part of the secretory pathway. http://togogenome.org/gene/10090:Or7g30 ^@ http://purl.uniprot.org/uniprot/Q8VFF6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Abcd4 ^@ http://purl.uniprot.org/uniprot/O89016 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.|||Endoplasmic reticulum membrane|||Homodimer or heterodimer. Interacts with LMBRD1; this interaction induces the translocation of ABCD4 from the ER to the lysosome membrane. Interacts with LMBRD1 and MMACHC; this interaction ensures the transport of cobalamin from the lysosome to the cytosol.|||Lysosomal membrane protein that transports cobalamin (Vitamin B12) from the lysosomal lumen to the cytosol in an ATP-dependent manner. Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane. Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane.|||Lysosome membrane|||Originally proposed to be a peroxisomal protein (By similarity). Recent studies have suggested its localization to the endoplasmic reticulum and within the lysosome (By similarity). http://togogenome.org/gene/10090:Pde3b ^@ http://purl.uniprot.org/uniprot/E9QLQ3|||http://purl.uniprot.org/uniprot/Q61409 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in adipose tissues.|||Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE3 subfamily.|||Binds 2 divalent metal cations per subunit.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:10454575). Regulates angiogenesis by inhibiting the cAMP-dependent guanine nucleotide exchange factor RAPGEF3 and downstream phosphatidylinositol 3-kinase gamma-mediated signaling (By similarity). Controls cardiac contractility by reducing cAMP concentration in cardiocytes (PubMed:15294162).|||Homodimer (By similarity). Interacts with PIK3CG; regulates PDE3B activity and thereby cAMP levels in cells (PubMed:15294162). Interacts with RAPGEF3 and PIK3R6; form a signaling complex that regulates phosphatidylinositol 3-kinase gamma in angiogenesis (By similarity). Interacts with ABHD15; this interaction regulates PDE3B's stability and expression and, thereby, impacts the antilipolytic action of insulin (PubMed:29768196).|||Inhibited by cGMP.|||Membrane|||Phosphorylation at Ser-273 mediates insulin-induced activation of PDE3B. http://togogenome.org/gene/10090:Or5p52 ^@ http://purl.uniprot.org/uniprot/A6H654|||http://purl.uniprot.org/uniprot/Q8VG43 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Osbpl3 ^@ http://purl.uniprot.org/uniprot/D3YTT6|||http://purl.uniprot.org/uniprot/D3Z194|||http://purl.uniprot.org/uniprot/F8WH20|||http://purl.uniprot.org/uniprot/Q9DBS9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OSBP family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed at higher levels in some regions of the developing central and peripheral nervous system, including hippocampal neuroepithelium, rhinencephalon, intermediate thalamus.|||Expressed in spinal ganglia. Expressed in a subset of small lymphocytes (at protein level).|||Homodimer (By similarity). Interacts with RRAS (By similarity). Interacts (phosphorylated form) with VAPA (By similarity). Interacts with OSBPL6 (PubMed:30028970).|||Nucleus membrane|||Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes. Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments. The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface. With VAPA, may regulate ER morphology. Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion. Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3. Also binds 25-hydroxycholesterol and cholesterol.|||Phosphorylation is enhanced in vitro by phorbol-12-myristate-13-acetate (PMA), forskolin and calcium ionophore A23187. Phosphorylation seems to be stimulated in conditions of low cell-cell (or cell-matrix) adhesion.|||The FFAT 2 motif is required for interaction with VAPA and regulation of the endoplasmic reticulum targeting of ORP3. The FFAT 1 motif may contribute to VAPA binding.|||The PH domain binds phosphoinositides, with a preference for PI(3,4)P2 and PI(3,4,5)P3. The PH domain mediates targeting to the plasma membrane.|||cytosol|||filopodium tip http://togogenome.org/gene/10090:Ptpn3 ^@ http://purl.uniprot.org/uniprot/A2ALK8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cell membrane|||May act at junctions between the membrane and the cytoskeleton.|||cytoskeleton http://togogenome.org/gene/10090:Cdh23 ^@ http://purl.uniprot.org/uniprot/Q99PF4 ^@ Disease Annotation|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic interaction with PCDH15.|||Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells. CDH23 is required for establishing and/or maintaining the proper organization of the stereocilia bundle of hair cells in the cochlea and the vestibule during late embryonic/early postnatal development. It is part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal hearing.|||Cell membrane|||Defects in Cdh23 are the cause of waltzer (v) phenotype. Waltzer mice are characterized by deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear.|||In adult animals relatively high levels of expression are found in testis, skeletal muscle, heart, eye and thymus, and lower expression in kidney, lung and brain. Found in the sensory hair cells of the inner ear.|||Interacts with USH1C and USH1G (By similarity). antiparallel heterodimer with PCDH15. Isoform C1: Interacts with CAMSAP3; leading to inhibit CAMSAP3 ability to induce microtubule bundle formation (PubMed:27349180).|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Cibar2 ^@ http://purl.uniprot.org/uniprot/Q3V2J0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CIBAR family.|||Homodimer (via BAR-like domain). Heterodimer (via BAR-like domain) with FAM92A. Interacts with CBY1.|||May play a role in ciliogenesis. In cooperation with CBY1 may facilitate ciliogenesis likely by the recruitment and fusion of endosomal vesicles at distal appendages during early stages of ciliogenesis.|||The BAR-like domain displays limited similarity to other BAR domains.|||centriole|||cilium basal body http://togogenome.org/gene/10090:Slc38a10 ^@ http://purl.uniprot.org/uniprot/Q5I012 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Expressed in neurons, astrocytes and epithelial cells scattered throughout the central nervous system structures including striatum, ependyma, cerebral cortex, hippocampus, hypothalamus, thalamus, pons, and cerebellum (at protein level). Highly expressed in paraventricular hypothalamic nucleus, suprachiasmatic nucleus, anterior hypothalamic area central part, in lateral ventricule and in dorsal 3rd ventricule (at protein level). Expressed in choroid plexus epithelial cells (at protein level).|||Facilitates bidirectional transport of amino acids. May act as a glutamate sensor that regulates glutamate-glutamine cycle and mTOR signaling in the brain. The transport mechanism remains to be elucidated.|||Membrane http://togogenome.org/gene/10090:Abcf2 ^@ http://purl.uniprot.org/uniprot/Q99LE6 ^@ Caution|||Similarity ^@ Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.|||Lacks transmembrane domains and is probably not involved in transport. http://togogenome.org/gene/10090:Prm2 ^@ http://purl.uniprot.org/uniprot/P07978|||http://purl.uniprot.org/uniprot/Q545M0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protamine P2 family.|||Chromosome|||Interacts with TDRP.|||Male mice are sterile due to reduced compaction of chromatin in sperm.|||Nucleus|||Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.|||Proteolytic processing into mature chains is required for histone eviction during spermatogenesis (PubMed:28366643). Transition proteins (TNP1 and TNP2) are required for processing (PubMed:28366643).|||Testis. http://togogenome.org/gene/10090:Or51m1 ^@ http://purl.uniprot.org/uniprot/F8VPJ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4a2 ^@ http://purl.uniprot.org/uniprot/Q8VGM8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tefm ^@ http://purl.uniprot.org/uniprot/Q5SSK3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TEFM family.|||Interacts with POLRMT.|||Mitochondrion matrix|||Transcription elongation factor which increases mitochondrial RNA polymerase processivity. Regulates transcription of the mitochondrial genome, including genes important for the oxidative phosphorylation machinery (By similarity).|||mitochondrion nucleoid http://togogenome.org/gene/10090:Patz1 ^@ http://purl.uniprot.org/uniprot/Q5NBZ1|||http://purl.uniprot.org/uniprot/Q80XS2|||http://purl.uniprot.org/uniprot/Q9JMG9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Iqsec3 ^@ http://purl.uniprot.org/uniprot/Q3TES0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a guanine nucleotide exchange factor (GEF) for ARF1.|||Belongs to the BRAG family.|||Cytoplasm|||Expressed specifically in the adult brain, but not in the fetal brain at 14 dpc.|||Interacts with DLG1 and DLG4 (By similarity). Interacts with GPHN (PubMed:27609886).|||Postsynaptic density http://togogenome.org/gene/10090:Hps5 ^@ http://purl.uniprot.org/uniprot/E9Q3X4|||http://purl.uniprot.org/uniprot/P59438|||http://purl.uniprot.org/uniprot/Q640Q9 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HPS5 family.|||Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6.|||Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS6 and HPS3. May interact with all alpha-integrin chains that have an aromatic residue before the first lysine of the conserved KXGFFKR motif, including ITGA2, ITGA3, ITGA5 and ITGA6.|||Defects in Hps5 are the cause of Hermansky-Pudlak-like syndrome, a syndrome characterized by hypopigmented eyes and coat, melanosomes greatly reduced in number and morphologically bizarre, kidney proximal tubules secreting lysosomal enzymes into urine at greatly reduced rates, platelet dense granules deficient in critical components, such as serotonin and adenine nucleotides, leading to functionally abnormal platelets and prolonged bleeding times, and mast cell granules undergoing unregulated 'kiss-and-run' fusion at the plasma membrane.|||May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.|||May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules. Regulates intracellular vesicular trafficking in fibroblasts. May be involved in the regulation of general functions of integrins.|||Widely expressed, with lowest expression in skeletal muscle and spleen.|||cytosol http://togogenome.org/gene/10090:Dok2 ^@ http://purl.uniprot.org/uniprot/O70469|||http://purl.uniprot.org/uniprot/Q3TX09 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the DOK family. Type A subfamily.|||DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK2 may modulate the cellular proliferation induced by IL-4, as well as IL-2 and IL-3. May be involved in modulating Bcr-Abl signaling. Attenuates EGF-stimulated MAP kinase activation.|||During embryonic liver development, expressed in the islands of cells, consistent with an expression in hematopoietic precursors.|||Highly expressed in spleen and lung.|||Interacts with phosphorylated RASGAP and EGFR. Interacts with RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine phosphorylated).|||On immunoreceptor stimulation, phosphorylated on C-terminal tyrosine residues. Phosphorylation on Tyr-351 is required for binding to the SH2 domain of NCK. Phosphorylation on both Tyr-276 and Tyr-304 is required for interaction with RASGAP. Phosphorylated on tyrosine residues by TEK/TIE2.|||PTB domain mediates receptor interaction. http://togogenome.org/gene/10090:Wasf3 ^@ http://purl.uniprot.org/uniprot/Q8VHI6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCAR/WAVE family.|||Binds actin and the Arp2/3 complex.|||Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain.|||Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity).|||Phosphorylation by ABL1 promotes lamellipodia formation and cell migration.|||cytoskeleton http://togogenome.org/gene/10090:Tmem70 ^@ http://purl.uniprot.org/uniprot/A0A0R4J272|||http://purl.uniprot.org/uniprot/Q921N7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM70 family.|||Higher expressed in the heart than in the liver (at protein level).|||Homooligomer. Interacts (homooligomer form) with ATP5MC1; this interaction facilitates the oligomer formation of subunit c/ATP5MC1 (c-ring) and the c-ring membrane insertion and also protects ATP5MC1 against intramitochondrial proteolysis. Interacts with the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 of the MCIA complex. Interacts with ATP5MC3, TMEM242 and TIMMDC1.|||Homozygous knockout mice for Tmem70 are embryonically lethal at about 9.5 days post coitum and exhibit profound growth retardation (PubMed:28173120). Embryos exhibit delayed development of the cardiovascular system and a disturbed heart mitochondrial ultrastructure, with concentric or irregular cristae structures (PubMed:28173120).|||Mitochondrion inner membrane|||Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by facilitating the membrane insertion and oligomer formation of the subunit c/ATP5MC1 through its interaction (By similarity). Therefore, participates in the early stage of mitochondrial ATP synthase biogenesis and also protects subunit c/ATP5MC1 against intramitochondrial proteolysis (PubMed:31652072, PubMed:28173120). In addition, binds the mitochondrial proton-transporting ATP synthase complexes I and may play a role in the stability of its membrane-bound subassemblies (By similarity). http://togogenome.org/gene/10090:Iapp ^@ http://purl.uniprot.org/uniprot/P12968 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calcitonin family.|||Interacts with IDE and INS.|||Secreted|||Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.|||The mature protein is largely unstructured in the absence of a cognate ligand, but contrary to the human protein, it does not easily form fibrillar aggregates. http://togogenome.org/gene/10090:Actr3 ^@ http://purl.uniprot.org/uniprot/Q3ULF7|||http://purl.uniprot.org/uniprot/Q99JY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with bacterium B.thailandensis BimA.|||ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. Seems to contact the pointed end of the daughter actin filament. In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs). Plays a role in ciliogenesis.|||Belongs to the actin family.|||Belongs to the actin family. ARP3 subfamily.|||Cell projection|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. Interacts with WHDC1. Interacts weakly with MEFV. Interacts with AVIL.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Slc2a13 ^@ http://purl.uniprot.org/uniprot/Q3UHK1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.|||Cell membrane|||H(+)-myo-inositol cotransporter. Can also transport related stereoisomers. http://togogenome.org/gene/10090:Crybb2 ^@ http://purl.uniprot.org/uniprot/P62696 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms (By similarity). http://togogenome.org/gene/10090:Or52h7 ^@ http://purl.uniprot.org/uniprot/B9EHE6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trim58 ^@ http://purl.uniprot.org/uniprot/Q5NCC9 ^@ Domain|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||E3 ubiquitin ligase induced during late erythropoiesis. Directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. May participate in the erythroblast enucleation process through regulation of nuclear polarization.|||Expressed in erythroblasts.|||The RING finger is required for ubiquitin ligase activity. http://togogenome.org/gene/10090:Nlrp4e ^@ http://purl.uniprot.org/uniprot/Q66X19 ^@ Function|||Similarity ^@ Belongs to the NLRP family.|||May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. http://togogenome.org/gene/10090:Dmrta2 ^@ http://purl.uniprot.org/uniprot/A2A9A2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DMRT family.|||Expressed from 12.5 dpc to 15.5 dpc in ovary and from 12.5 dpc to 14.5 dpc in testis, but to a lower extent. Expression is detectable in early embryos at 8.5 dpc and in brain of embryos at 13.5 dpc.|||Expressed in adult brain and testis, as well as in embryonic ovary, kidney, heart, lung, stomach and brain.|||May be involved in sexual development.|||Nucleus http://togogenome.org/gene/10090:Tmem92 ^@ http://purl.uniprot.org/uniprot/B7ZWI3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Amer2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J030|||http://purl.uniprot.org/uniprot/Q8CCJ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Amer family.|||Cell membrane|||Interacts with APC.|||Negative regulator of the canonical Wnt signaling pathway involved in neuroectodermal patterning. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex (By similarity). http://togogenome.org/gene/10090:Atox1 ^@ http://purl.uniprot.org/uniprot/O08997 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the ATX1 family.|||Binds and deliver cytosolic copper to the copper ATPase proteins. May be important in cellular antioxidant defense (By similarity).|||Homodimer. Interacts with ATP7B. Interacts with ATP7A. Interacts (via dimer form) with SLC31A1 (via C-terminal domain); this interaction improves ATOX1 stability and controls intracellular Cu(I) levels.|||The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion via the cysteine residues within the CXXC motif. The transfer of Cu(+) ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu(+)-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu(+) ion. http://togogenome.org/gene/10090:Polr3g ^@ http://purl.uniprot.org/uniprot/Q6NXY9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic RPC7 RNA polymerase subunit family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. RPC3/POLR3C, RPC6/POLR3F and RPC7/POLR3G form a Pol III subcomplex. Directly interacts with POLR3C/RPC62. Also found a trimeric complex with POLR3C and POLR3GL.|||Cytoplasm|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. May direct with other members of the RPC3/POLR3C-RPC6/POLR3F-RPC7/POLR3G subcomplex RNA Pol III binding to the TFIIIB-DNA complex via the interactions between TFIIIB and POLR3F. May be involved either in the recruitment and stabilization of the subcomplex within RNA polymerase III, or in stimulating catalytic functions of other subunits during initiation. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway.|||Expressed at low levels in the liver.|||Not detectable in unfertilized oocytes. First detected in zygotes and the 2-cell stage embryos. Expressed until at least the early blastocyst stage.|||Nucleus http://togogenome.org/gene/10090:Cfd ^@ http://purl.uniprot.org/uniprot/P03953 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Pus7 ^@ http://purl.uniprot.org/uniprot/Q3ULP8|||http://purl.uniprot.org/uniprot/Q91VU7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pseudouridine synthase TruD family.|||Interacts with SIRT1.|||Nucleus|||Pseudouridylate synthase that catalyzes pseudouridylation of RNAs. Acts as a regulator of protein synthesis in embryonic stem cells by mediating pseudouridylation of RNA fragments derived from tRNAs (tRFs): pseudouridylated tRFs inhibit translation by targeting the translation initiation complex. Also catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of mRNAs with the consensus sequence 5'-UGUAG-3'. Acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions. Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3'-end processing. In addition to mRNAs and tRNAs, binds other types of RNAs, such as snRNAs, Y RNAs and vault RNAs, suggesting that it can catalyze pseudouridylation of many RNA types. http://togogenome.org/gene/10090:Chrm4 ^@ http://purl.uniprot.org/uniprot/P32211|||http://purl.uniprot.org/uniprot/Q0VBU3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily.|||Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane|||The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.|||The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase. http://togogenome.org/gene/10090:Trpv1 ^@ http://purl.uniprot.org/uniprot/Q3V318|||http://purl.uniprot.org/uniprot/Q704Y3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV1 sub-subfamily.|||Cell membrane|||Detected in neurons in the root ganglia (at protein level). Detected in dorsal root ganglia.|||Homotetramer. May also form a heteromeric channel with TRPV3 (By similarity). Interacts with CALM, PRKCM and CSK (By similarity). Interacts with PRKCG and NTRK1, probably by forming a trimeric complex (By similarity). Interacts with PIRT (PubMed:18455988). Interacts with the Scolopendra mutilans RhTx toxin (PubMed:26420335). Interacts with TMEM100 (PubMed:25640077). Interacts with PACS2 (By similarity).|||Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli (PubMed:15194687, PubMed:15489017). Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia (PubMed:10764638). Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis (By similarity).|||Membrane|||Mice are viable and fertile, but lack behavorial and physiological responses to capsaicin and show impaired responses to noxious heat stimuli. Their dorsal root ganglion neurons do not display calcium channel activation in response to capsaicin or resiniferatoxin. Likewise, their dorsal root ganglion neurons do not display calcium channel activitation in response to low extracellular pH.|||Phosphorylation by PKA reverses capsaicin-induced dephosphorylation at multiple sites probably including Ser-117 as a major phosphorylation site. Phosphorylation by CAMKII seems to regulate binding to vanilloids. Phosphorylated and modulated by PRKCE, PRKCM and probably PRKCZ. Dephosphorylation by calcineurin seems to lead to receptor desensitization and phosphorylation by CAMKII recovers activity.|||Postsynaptic cell membrane|||The association domain (AD) is necessary for self-association.|||The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation (By similarity). The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (PubMed:26420335). Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity. Intracellular PIP2 inhibits desensitization (By similarity).|||dendritic spine membrane http://togogenome.org/gene/10090:Rpn2 ^@ http://purl.uniprot.org/uniprot/Q9DBG6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SWP1 family.|||Component of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (By similarity). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes. Interacts with DDI2 (By similarity). Interacts with TMEM35A/NACHO (PubMed:32783947).|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. http://togogenome.org/gene/10090:Twsg1 ^@ http://purl.uniprot.org/uniprot/Q9EP52 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the twisted gastrulation protein family.|||Embryonic lethality and sirenomelia were observed only in BMP null embryos in which one or two copies of TSG were also missing. When TSG and BMP7 are mutated, the siren phenotype results from the fusion of the limb buds in the ventroposterior midline owing to a paucity of posterior ventral mesoderm.|||Expressed at all embryonic stages examined. Expression was low and distribution was diffuse. At the primitive streak stage, detected in the extraembryonic region. Signal first appeared in the embryo during the neural plate stage. Stronger and more localized expression is seen after embryonic turning. Higher expression is seen in the branchial arch mesenchyme, the endoderm of the developing pharynx, all levels of the developing gut, the myotome compartment of the somites, and some regions of surface ectoderm. At 8.25 and 9.0 dpc expressed in head mesenchyme and ventral mesoderm.|||Expressed in lymph node, liver, kidney, and lung. Expression in the kidney was stronger in the medulla than in the cortex, particularly in the cells surrounding the medullary tubules. Expressed in growth plate cartilage of long bones, ribs, and digits and to a lesser extent also in the resting zone of the epiphysis, trabecular bone, and vertebral cartilage. Expression seems to be absent from other skeletal tissues including muscle, skin, and fibroblasts.|||Interacts with CHRD and/or BMP4. This interaction enhances CHRD/BMP4 complex formation. Interacts with BMP7.|||May be involved in dorsoventral axis formation. Seems to antagonize BMP signaling by forming ternary complexes with CHRD and BMPs, thereby preventing BMPs from binding to their receptors. In addition to the anti-BMP function, also has pro-BMP activity, partly mediated by cleavage and degradation of CHRD, which releases BMPs from ternary complexes. May be an important modulator of BMP-regulated cartilage development and chondrocyte differentiation. May play a role in thymocyte development.|||Secreted|||The N-terminal domain is sufficient to interact with BMP4. http://togogenome.org/gene/10090:Efcab2 ^@ http://purl.uniprot.org/uniprot/Q9CQ46 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DRC8 family.|||Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.|||Component of the nexin-dynein regulatory complex (N-DRC).|||flagellum axoneme http://togogenome.org/gene/10090:N4bp1 ^@ http://purl.uniprot.org/uniprot/Q6A037 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the N4BP1 family.|||Interacts with NEDD4 (PubMed:11717310). Interacts with ITCH (via WW domain 2) (PubMed:17592138).|||Mice are viable, fertile and grossly normal, but develop mild, age-dependent inflammation and immune dysregulation.|||Mono- and polyubiquitinated on the CoCUN region (By similarity). Monoubiquitinated by NEDD4 (PubMed:11717310). Polyubiquitinated, leading to its degradation by the proteasome (PubMed:20233849). Sumoylated with SUMO1, abrogating polyubiquitination and subsequent degradation (PubMed:20233849). Desumoylated by SENP1, leading to accumulation in PML nuclear bodies (PubMed:20233849).|||Nucleus|||PML body|||Potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation (PubMed:32971525). Acts as a key negative regulator of select cytokine and chemokine responses elicited by TRIF-independent Toll-like receptors (TLRs), thereby limiting inflammatory cytokine responses to minor insults (PubMed:32971525). In response to more threatening pathogens, cleaved by CASP8 downstream of TLR3 or TLR4, leading to its inactivation, thereby allowing production of inflammatory cytokines (PubMed:32971525). Acts as a restriction factor against some viruses: restricts viral replication by binding to mRNA viruses and mediating their degradation via its ribonuclease activity (By similarity). Also acts as an inhibitor of the E3 ubiquitin-protein ligase ITCH: acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates (PubMed:17592138).|||Proteolytic cleavage by CASP8 or MALT1 leads to its inactivation.|||Proteolytically cleaved by CASP8 downstream of TLR3 or TLR4, leading to its inactivation (PubMed:32971525). Mainly cleaved at Asp-488 by CASP8 (PubMed:32971525). Cleaved by caspase-like protein MALT1, leading to its inactivation (By similarity).|||The CoCUN region mediates binding to ubiquitin. Does not interact with NEDD8.|||cytosol|||nucleolus http://togogenome.org/gene/10090:Lhx3 ^@ http://purl.uniprot.org/uniprot/A2ALD8|||http://purl.uniprot.org/uniprot/P50481 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed throughout pituitary development (PubMed:7811383, PubMed:7708713). Detected at 11 dpc in the primordium of the hypophysis (PubMed:7811383). Following a maximum between 12 dpc and 14 dpc, lower levels persisted into adulthood (PubMed:7811383, PubMed:7708713). Expressed at 11.5 dpc and 12.5 dpc in developing spinal cord, especially in motor neurons (at protein level) (PubMed:18539116).|||Interacts with POU1F1 (By similarity). At neuronal promoters, interacts with LDB1, in motor neurons LDB1 is displaced by ISL1 and a ternary complex is formed in which ISL1 contacts both LHX3 and LDB1; allosteric structural changes in the DNA binding domain of LHX3, induced by the ISL1-LHX3 interaction, may explain differences in sequence specificity of the different complexes (PubMed:12150931, PubMed:18583962, PubMed:18539116). Interacts with LDB2 (PubMed:9192866). May interact with CITED2/MRG1 (PubMed:10593900).|||Mostly expressed in the pituitary anterior and intermediate lobes (PubMed:7811383). It is also expressed in the pineal gland and transiently in the primordia of motor neurons including the spinal cord, pons and medulla oblongata (PubMed:7811383, PubMed:7708713).|||Nucleus|||The LIM domain specifically interacts with the POU1F1/Pit-1 POU domain and is required for synergistic interactions with POU1F1, but not for basal transcriptional activation events.|||Transcription factor (PubMed:18539116, PubMed:10593900, PubMed:12150931). Recognizes and binds to the consensus sequence motif 5'-AATTAATTA-3' in the regulatory elements of target genes, such as glycoprotein hormones alpha chain CGA and visual system homeobox CHX10, positively modulating transcription; transcription can be co-activated by LDB2 (PubMed:18539116, PubMed:10593900, PubMed:9192866). Synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (PubMed:7708713). Required for the establishment of the specialized cells of the pituitary gland and the nervous system (By similarity). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1 (PubMed:12150931, PubMed:18539116). http://togogenome.org/gene/10090:Gins3 ^@ http://purl.uniprot.org/uniprot/Q9CY94 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GINS3/PSF3 family.|||Chromosome|||Component of the GINS complex which is a heterotetramer of GINS1, GINS2, GINS3 and GINS4. Forms a stable subcomplex with GINS2. GINS complex interacts with DNA primase in vitro. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex.|||Nucleus|||Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. http://togogenome.org/gene/10090:Capzb ^@ http://purl.uniprot.org/uniprot/P47757|||http://purl.uniprot.org/uniprot/Q923G3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the F-actin-capping protein beta subunit family.|||F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.|||F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity).|||Heterodimer of an alpha and a beta subunit.|||Heterodimer of an alpha and a beta subunit. Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with ARHGAP17. Interaction with RCSD1/CAPZIP. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASH (WASHC1, WASH2P, WASH3P, WASH4P, WASH5P or WASH6P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. Interacts with ACTG1. Directly interacts with CRACD; this interaction decreases binding to actin (By similarity).|||Isoform 3 is first detected in testis 22 days after birth, coinciding with the first wave of round spermatid development. It is also detected on 30 and 60 days after birth.|||Isoform 3 is testis-specific and is present in round spermatids, but not in pachytene spermatocytes or Sertoli cells.|||Z line|||calyx|||cytoskeleton|||sarcomere http://togogenome.org/gene/10090:Slc22a13 ^@ http://purl.uniprot.org/uniprot/Q6A4L0 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Anion antiporter that mediates the transport of orotate and nicotinate in exchange for organic or inorganic anions (PubMed:35144162). Translocates orotate across the apical membrane of proximal tubule epithelial cells. Possibly involved in orotate renal reabsorption and nicotinate intestinal reabsorption (PubMed:35144162). Orotate transport is Cl(-)-dependent (By similarity).|||Apical cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Glycosylated.|||In contrast with human ortholog, not able to transport urate (PubMed:35144162). http://togogenome.org/gene/10090:Ralgps2 ^@ http://purl.uniprot.org/uniprot/Q9ERD6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in brain and testis.|||Cell membrane|||Cytoplasm|||Guanine nucleotide exchange factor for the small GTPase RALA. May be involved in cytoskeletal organization. May also be involved in the stimulation of transcription in a Ras-independent fashion.|||Interacts with RALA (By similarity). Interacts with the SH3 domains of GRB2 and PLCG1.|||The PH domain mediates binding to phosphatidylinositol 4,5-bisphosphate. http://togogenome.org/gene/10090:Ncf2 ^@ http://purl.uniprot.org/uniprot/O70145 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NCF2/NOXA1 family.|||Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4 (By similarity). Interacts with NCF4 (PubMed:21551061). Interacts (via the C-terminal SH3 domain) with NCF1 (via C-terminus). Interacts with SYTL1 and RAC1. May interact with NOXO1. Interacts with S100A8 and calprotectin (S100A8/9) (By similarity). Interacts with GBP7 (via GB1/RHD3-type G domain) (PubMed:21551061). Interacts with CYBB; the interaction is enhanced in the presence of GBP7 (PubMed:21551061).|||Cytoplasm|||NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).|||The OPR/PB1 domain mediates the association with NCF4/p40-PHOX. http://togogenome.org/gene/10090:Kcnj2 ^@ http://purl.uniprot.org/uniprot/P35561|||http://purl.uniprot.org/uniprot/Q543W5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily.|||Homomultimeric and heteromultimeric association with KCNJ4/Kir2.3. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking (By similarity).|||Membrane|||Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium.|||Prominently expressed in the central nervous system. Also found in other excitable tissues such as heart and skeletal muscle.|||S-nitrosylation increases the open probability and inward rectifying currents. http://togogenome.org/gene/10090:Ahsg ^@ http://purl.uniprot.org/uniprot/P29699 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fetuin family.|||Liver is the major site of synthesis, but fetuin is also expressed in limb buds and other extrahepatic tissues during development.|||Phosphorylated by FAM20C in the extracellular medium.|||Probably involved in differentiation.|||Secreted http://togogenome.org/gene/10090:Mrtfb ^@ http://purl.uniprot.org/uniprot/P59759 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional coactivator of serum response factor (SRF). Required for skeletal myogenic differentiation.|||Detected throughout the embryo at 10.5 dpc. High expression in epithelial cells of the lung, kidney, bladder, colon, testis, in the smooth muscle of the colon and small intestines, and in the mesenchymal cells adjacent to the olfactory epithelium at 15.5 dpc.|||Interacts with MRTFA and SRF.|||Nucleus|||O-glycosylated.|||The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity.|||Widely expressed. High expression in heart, brain and testis. Lower expression in lung, liver and kidney. http://togogenome.org/gene/10090:Dennd1a ^@ http://purl.uniprot.org/uniprot/Q8K382 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Guanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Regulates clathrin-mediated endocytosis of synaptic vesicles and mediates exit from early endosomes (PubMed:17182770, PubMed:20159556). Binds phosphatidylinositol-phosphates (PtdInsPs), with some preference for PtdIns(3)P (PubMed:20159556).|||Interacts with RAB35 (PubMed:20159556). Interacts with clathrin and with the adapter protein complex 2, AP-2 (By similarity). Interacts with ITSN1 and SH3GL2 (PubMed:17182770). Interacts (when phosphorylated) with YWHAE (By similarity).|||Phosphorylated on serine and/or threonine in an Akt-dependent manner. Phosphorylation probably regulates the guanine nucleotide exchange factor (GEF) activity, possibly by disrupting an intramolecular interaction between the DENN domain and the C-terminus of the protein, thereby relieving the autoinhibition.|||Presynaptic cell membrane|||The guanine nucleotide exchange factor (GEF) activity is autoinhibited. Autoinhibition may be the result of intramolecular interaction between the DENN domain and the C-terminus, which is disrupted upon phosphorylation. Activation is regulated by Akt activation.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Ppp1r1a ^@ http://purl.uniprot.org/uniprot/Q9ERT9 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the protein phosphatase inhibitor 1 family.|||Inhibitor of protein-phosphatase 1. This protein may be important in hormonal control of glycogen metabolism. Hormones that elevate intracellular cAMP increase I-1 activity in many tissues. I-1 activation may impose cAMP control over proteins that are not directly phosphorylated by PKA. Following a rise in intracellular calcium, I-1 is inactivated by calcineurin (or PP2B). Does not inhibit type-2 phosphatases.|||Interacts with PPP1R15A.|||Phosphorylation of Thr-35 is required for activity. http://togogenome.org/gene/10090:Snx33 ^@ http://purl.uniprot.org/uniprot/Q4VAA7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sorting nexin family.|||Cytoplasmic vesicle membrane|||Detected in brain (at protein level).|||Homodimer (via BAR domain). Interacts with ADAM15. Interacts with FASLG. Interacts (via SH3 domain) with DNM1 and DNM2. Interacts with WASL (By similarity). Interacts with FCHSD1 (via the F-BAR domain) (PubMed:26567222).|||Membrane|||Phosphorylated.|||Plays a role in the reorganization of the cytoskeleton, endocytosis and cellular vesicle trafficking via its interactions with membranes, WASL, DNM1 and DNM2. Acts both during interphase and at the end of mitotic cell divisions. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Modulates endocytosis of cell-surface proteins, such as APP and PRNP; this then modulates the secretion of APP and PRNP peptides. Promotes membrane tubulation (in vitro). May promote the formation of macropinosomes (By similarity).|||The PX and BAR domains mediate association with membranes and are required for membrane tubulation.|||cytosol http://togogenome.org/gene/10090:Casq2 ^@ http://purl.uniprot.org/uniprot/O09161 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calsequestrin family.|||Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, especially at the interface between subunits. Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats.|||Detected in heart (at protein level). Detected in heart.|||Monomer, homodimer and homooligomer. Mostly monomeric in the absence of calcium. Forms higher oligomers in a calcium-dependent manner. Dimers associate to form tetramers, that then form linear homomer chains. Interacts with ASPH and TRDN (By similarity).|||Mutant mice are born at the expected Mendelian rate, are viable and display normal sarcoplasmic calcium release and normal heart function under basal conditions, but have a slower heart rate. Mutant mice are subject to polymorphic arrhythmia after exercise and to catecholaminergic ventricular arrhythmia, and their myocytes show increased Ca(2+) release in response to isoproterenol. Besides, the volume of the junctional sarcoplasmic reticulum is increased, and it seems to lack visible content.|||N-glycosylated.|||Phosphorylation in the C-terminus moderately increases calcium buffering capacity.|||Sarcoplasmic reticulum lumen http://togogenome.org/gene/10090:Rpap3 ^@ http://purl.uniprot.org/uniprot/Q9D706 ^@ Function|||Similarity|||Subunit ^@ Belongs to the RPAP3 family.|||Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation.|||Tightly associated with the RNA polymerase II complex (By similarity). Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1 (By similarity). Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (By similarity). Interacts with PIH1D1 (By similarity). Interacts with TSC1 and TSC2 (By similarity). Interacts with PRPF8 and EFTUD2 in a ZNHIT2-dependent manner (By similarity). http://togogenome.org/gene/10090:Adgrv1 ^@ http://purl.uniprot.org/uniprot/B8JJE0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ciita ^@ http://purl.uniprot.org/uniprot/P79621 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated, affecting interaction with TAF7.|||By IFNG and LPS (PubMed:32855215, PubMed:9184229). By STAT1 in the upper small intestine (PubMed:37327784).|||Detected at high levels in spleen and tonsil as well as in a number of B-lymphocyte cell lines, and at very low levels in dendritic cells.|||Essential for transcriptional activity of the HLA class II promoter; activation is via the proximal promoter (PubMed:37327784). Does not bind DNA (By similarity). May act in a coactivator-like fashion through protein-protein interactions by contacting factors binding to the proximal MHC class II promoter, to elements of the transcription machinery, or both (By similarity). Alternatively it may activate HLA class II transcription by modifying proteins that bind to the MHC class II promoter (By similarity). Also mediates enhanced MHC class I transcription, the promoter element requirements for CIITA-mediated transcription are distinct from those of constitutive MHC class I transcription, and CIITA can functionally replace TAF1 at these genes (By similarity). Activates CD74 transcription (PubMed:32855215). Exhibits intrinsic GTP-stimulated acetyltransferase activity (By similarity). Exhibits serine/threonine protein kinase activity: phosphorylates the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF, histone H2B at 'Ser-37' and other histones (By similarity).|||Expressed at very high levels in dendritic cells, at very low levels in spleen and thymus and is not detected in other tissues.|||Interacts with ZXDA and ZXDC. Interacts with PML (isoform PML-2). Interacts with TAF7; interaction inhibits CIITA acetyltransferase activity, thereby repressing transcription.|||Nucleus|||PML body|||The GTP-binding motif doesn't confer GTPase activity but promotes nuclear localization.|||The acetyltransferase domain is necessary for activation of both class I and class II transcription. http://togogenome.org/gene/10090:Tmem114 ^@ http://purl.uniprot.org/uniprot/Q9D563 ^@ Developmental Stage|||Subcellular Location Annotation ^@ Cell membrane|||Expressed weakly in the eye from as early as 13.5 dpc, with ocular expression up-regulated postnatally. By 10 weeks, expressed strongly in the lens epithelial cells and weakly in lens fibers. In adult, expressed in eye, brain and testis. http://togogenome.org/gene/10090:Abca3 ^@ http://purl.uniprot.org/uniprot/Q3TN91|||http://purl.uniprot.org/uniprot/Q6AXE3|||http://purl.uniprot.org/uniprot/Q8R420 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCA family.|||Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant (PubMed:17577581, PubMed:17540762, PubMed:17267394, PubMed:17142808, PubMed:20190032, PubMed:28034695). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:17142808). In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity (By similarity).|||Cytoplasmic vesicle membrane|||Highly expressed in the lung and moderately expressed in the kidney, adipose, macrophage, and spleen.|||Homooligomer; disulfide-linked.|||Homozygous knockout mice for ABCA3 are die within one hour after birth (PubMed:17577581, PubMed:17540762, PubMed:17267394). Mice develop respiratory failure immediately after birth with clinical signs such as gasping, cyanosis, failure to achieve inflation of the lung as visible through the skin and reduced motor activity and (PubMed:17577581, PubMed:17142808, PubMed:17267394). Conditional knockout mice in which ABCA3 is deleted in alveolar type II cells die shortly after birth from respiratory distress related to surfactant deficiency but approximately 30% of these mice survive after birth and develop emphysema in the absence of significant pulmonary inflammation (PubMed:20190032).|||Late endosome membrane|||Lysosome membrane|||Membrane|||Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.|||N-glycosylated. Localization at intracellular vesicles is accompanied by processing of oligosaccharide from high mannose type to complex type. N-linked glycosylation at Asn-124 and Asn-140 is required for stability and efficient anterograde trafficking and prevents from proteasomal degradation.|||Proteolytically cleaved by CTSL and to a lower extent by CTSB within multivesicular bodies (MVB) and lamellar bodies (LB) leading to a mature form of 150 kDa.|||multivesicular body membrane http://togogenome.org/gene/10090:Tmc6 ^@ http://purl.uniprot.org/uniprot/B1ATB3|||http://purl.uniprot.org/uniprot/Q7TN60 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMC family.|||Endoplasmic reticulum membrane|||Interacts with CIB1.|||Membrane|||Probable ion channel.|||Widely expressed. http://togogenome.org/gene/10090:Nat8f3 ^@ http://purl.uniprot.org/uniprot/Q9JIY8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||Cytoplasm|||Has histone acetyltransferase activity in vitro, with specificity for histone H4.|||Nucleus membrane|||perinuclear region http://togogenome.org/gene/10090:Ldhb ^@ http://purl.uniprot.org/uniprot/A0A6I8MX27|||http://purl.uniprot.org/uniprot/P16125 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LDH/MDH superfamily. LDH family.|||Cytoplasm|||Homotetramer. Interacts with PTEN upstream reading frame protein MP31; the interaction leads to inhibition of mitochondrial lactate dehydrogenase activity, preventing conversion of lactate to pyruvate in mitochondria.|||Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:F2rl1 ^@ http://purl.uniprot.org/uniprot/P55086|||http://purl.uniprot.org/uniprot/Q3TU81 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand. Activating serine proteases include trypsin, mast cell tryptase, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine protease 1/ST14. Proposed subsequent cleavage by serine proteases is leading to receptor deactivation and include neutrophil elastase and cathepsin G. At least in part, implicated proteases are also shown to activate the receptor; the glycosylation status of the receptor is thought to contribute to the difference.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Delayed onset of inflammation. Reduced progression of osteoarthritis, infectious colitis, allergic dermatitis and experimental autoimmune encephalomyelitis. Upon induced allergic and toxic contact dermatitis ear swelling responses, plasma extravasation and leuocyte adherence are significantly attenuated. Upon ovalbumin (OA) sensitization and following challenge infiltration of eosinophils and increase of eotaxin content in bronchoalveolar lavage fluid are abrogated.|||Interacts with TLR4, COPS5 and TMED2 (By similarity). Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14.|||Membrane|||Monoubiquitinated by Cbl at the plasma membrane and in early endosomes; not required for receptor endocytosis but for translocation to late endosomes or lysosomes. Deubiquitination involves Stambp and Usp8; required for lysosomal trafficking and receptor degradation (By similarity).|||Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin.|||N-glycosylated and sialylated.|||Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2r/Par1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with Tlr4 and probably Tlr2 in inflammatory responses and modulates Tlr3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3 (By similarity). Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o)-alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of Ripk1 and Tradd from Tnfr1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves Ikbkb and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of GNAQ and GNA11 and involves promotion of cofilin dephosphorylation and actin filament severing. Induces redistribution of Cops5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by Cops5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as pro-inflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses (By similarity).|||Synthetic PAR agonist peptides (APs) that mimic the first six amino acids of the newly formed N-terminus activate the native, uncleaved receptor nonenzymatically by binding directly to the corresponding second extracellular loop to mediate signaling. http://togogenome.org/gene/10090:Vstm4 ^@ http://purl.uniprot.org/uniprot/T1NXB5 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Peptide Lv enhances L-type voltage-gated calcium channel (L-VGCC) currents in retinal photoreceptors.|||Peptide Lv is widely expressed in various tissues and the central nervous system, including the retinal photoreceptor layer, hippocampus, olfactory bulb, and cerebellum.|||Proteolytically cleaved to generate a bioactive peptide.|||Secreted http://togogenome.org/gene/10090:Ttc23l ^@ http://purl.uniprot.org/uniprot/A6H6E9 ^@ Subcellular Location Annotation ^@ Midbody|||centrosome|||spindle http://togogenome.org/gene/10090:Or8u9 ^@ http://purl.uniprot.org/uniprot/Q8VGR9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Tcf21 ^@ http://purl.uniprot.org/uniprot/O35437 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3 and binds the E box (5'-CANNTG-3').|||Expressed at high levels in lung, kidney, gut, heart, ovary and podocytes (visceral glomerular epithelial cells). Also found in spleen, large intestine, uterus, bladder and testis.|||Expressed during embryogenesis specifically in mesodermally-derived cells that surround the epithelium of the developing gastrointestinal, genitourinary, respiratory systems and in spiral septum of the heart and in epicardial precursor cells fated to form the coronary arteries. Expression pattern is sex- and stage-dependent during gonadogenesis. At 13.5 dpc expressed at higher levels in testis than ovary. In 3-month old adults expression drastically decreased in testis while it increased in ovary showing an opposite sex-dependent pattern in adults compared with fetuses. Expression in other organs was similar between the adults and the fetal stage.|||Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis. May be involved in the organogenesis of the spleen and heart and in cardiac and coronary artery development. May function in the development and sex differentiation of gonad via transcriptional regulation of AD4BP/SF-1.|||Nucleus http://togogenome.org/gene/10090:Ints8 ^@ http://purl.uniprot.org/uniprot/Q80V86 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 8 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (By similarity).|||Highly expressed in the brain at 14.5 dpc especially in the cortex ventricular zone and hindbrain.|||Nucleus http://togogenome.org/gene/10090:Pcgf2 ^@ http://purl.uniprot.org/uniprot/P23798 ^@ Developmental Stage|||Disease Annotation|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Developmentally regulated.|||Exists as both a monomer and homodimer (PubMed:12480532). Component of a PRC1-like complex. Interacts with CBX8, RING1 and RNF2 (By similarity). Interacts with CBX7 (PubMed:22226355). Interacts with PHC2 (PubMed:16024804).|||Expressed in embryonic stem cells (PubMed:22226355). Expressed in a variety of tumor cells and in neural tissues (PubMed:2246278).|||Nucleus|||Phosphorylated. Homodimer formation is regulated by phosphorylation with only unphosphorylated proteins forming homodimers.|||Probably related to tumorigenesis since it is expressed strongly in most tumor cell lines.|||Transcriptional repressor (PubMed:8521824). Binds specifically to the DNA sequence 5'-GACTNGACT-3' (PubMed:8521824). Has tumor suppressor activity (PubMed:8521824). May play a role in control of cell proliferation and/or neural cell development (Probable). Regulates proliferation of early T progenitor cells by maintaining expression of HES1(PubMed:15728456). Also plays a role in antero-posterior specification of the axial skeleton and negative regulation of the self-renewal activity of hematopoietic stem cells (PubMed:8625838, PubMed:15183898). Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity (By similarity). http://togogenome.org/gene/10090:Slc28a3 ^@ http://purl.uniprot.org/uniprot/Q9ERH8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.|||Cell membrane|||Homotrimer.|||Sodium-dependent, pyrimidine- and purine-selective (PubMed:11032837). Involved in the homeostasis of endogenous nucleosides (PubMed:11032837). Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtype (N3/cib) (with marked transport of both thymidine and inosine) (PubMed:11032837). Employs a 2:1 sodium/nucleoside ratio (PubMed:11032837). Also able to transport gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin and 3-deazauridine (By similarity). http://togogenome.org/gene/10090:Clca4a ^@ http://purl.uniprot.org/uniprot/A0A5F8MQB6 ^@ Similarity ^@ Belongs to the CLCR family. http://togogenome.org/gene/10090:Ythdf1 ^@ http://purl.uniprot.org/uniprot/P59326 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YTHDF family. YTHDF1 subfamily.|||Cytoplasm|||In brain, preferentially expressed in the hippocampus.|||Interacts with CNOT1; promoting recruitment of the CCR4-NOT complex (By similarity). Interacts with ribosomes (By similarity). Interacts with eIF3 (EIF3A or EIF3B). Interacts with YTHDF3 (By similarity).|||Mice are viable and were born at the expected Mendelian ratio (PubMed:32943573). They however display learning and memory defects (PubMed:30401835). Mice develop normally up to four months of age and have normal gross hippocampal histology (PubMed:30401835). They however show learning and memory defects as well as impaired hippocampal synaptic transmission and long-term potentiation (PubMed:30401835). Hippocampal CA1 neurons show reduced dendritic spine density but unaltered spine size (PubMed:30401835). Conditional deletion in spinal commissural neurons results in pre-crossing axon guidance defects (PubMed:30843071). Knockout mice show an improved tumor control associated with increased infiltration of the tumor by T-cells, due to elevated antigen-specific CD8(+) T-cell anti-tumor response (PubMed:30728504). Conditional deletion in myeloid dendritic cells causes increased cross-presentation of tumor antigens and the cross-priming of CD8(+) T-cells (PubMed:30728504). Mice lacking Ythdf1, Ythdf2 and Ythdf3 display early embryonic lethality and show defects in embryonic stem cell differentiation (PubMed:32943573).|||P-body|||Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, and regulates their stability (PubMed:30401835, PubMed:32943573). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:30401835, PubMed:32943573). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex (By similarity). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:32943573). Required to facilitate learning and memory formation in the hippocampus by binding to m6A-containing neuronal mRNAs (PubMed:30401835). Acts as a regulator of axon guidance by binding to m6A-containing ROBO3 transcripts (PubMed:30843071). Acts as a negative regulator of antigen cross-presentation in myeloid dendritic cells (PubMed:30728504). In the context of tumorigenesis, negative regulation of antigen cross-presentation limits the anti-tumor response by reducing efficiency of tumor-antigen cross-presentation (PubMed:30728504). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (By similarity). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (By similarity).|||Stress granule|||The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons.|||Was initially reported to act as a regulator of mRNA translation efficiency by promoting ribosome loading to m6A-containing mRNAs and by interacting with translation initiation factors eIF3 (EIF3A or EIF3B), thereby facilitating translation initiation (PubMed:30401835, PubMed:30728504, PubMed:30843071). These studies suggested that the 3 different paralogs (YTHDF1, YTHDF2 and YTHDF3) have unique functions with limited redundancy (PubMed:30401835, PubMed:30728504, PubMed:30843071). However, later studies showed that YTHDF1, YTHDF2 and YTHDF3 paralogs have redundant functions to a profound extent and directly promote degradation of m6A-containing mRNAs (PubMed:32943573). The effect on translation efficiency observed earlier is probably indirect (PubMed:32943573). http://togogenome.org/gene/10090:Arl14 ^@ http://purl.uniprot.org/uniprot/S4R1T9 ^@ Similarity ^@ Belongs to the small GTPase superfamily. Arf family. http://togogenome.org/gene/10090:Isg20 ^@ http://purl.uniprot.org/uniprot/Q9JL16 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with PML and SP100 in the PML NB complex. Associates with survival motor neuron protein (SMN)-containing macromolecular nuclear complexes and U1 and U2 snRNAs and U3 snoRNA (By similarity).|||Belongs to the exonuclease superfamily.|||Binds 2 manganese ions per subunit.|||Cajal body|||Cytoplasm|||ISG20-deletion mice exhibit higher mortality following vesicular stomatitis virus challenge (PubMed:31600344). They also show a slightly earlier onset of symptoms when infected with venezuelan equine encephalitis virus. However, weight loss and the median survival times for infected mice are essentially equivalent between the deletion mutant and the WT.|||Induced by interferons alpha and beta. Weaker induction was seen with interferon gamma. Increased expression was seen at the transcriptional level (By similarity).|||Interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA. Inhibition of several viruses does not involve the degradation of viral RNAs, but rather the inhibition of translation of viral proteins (PubMed:30232164). Exerts a translational control over a large panel of non-self RNA substrates while sparing endogenous transcripts. This activity correlates with the protein's ability to localize in cytoplasmic processing bodies (PubMed:31600344). May also act as master regulator of over hundred interferon stimulated genes leading to viral genome translation inhibition (PubMed:30232164). May play additional roles in the maturation of snRNAs and rRNAs, and in ribosome biogenesis (By similarity).|||Nucleus|||P-body|||nucleolus http://togogenome.org/gene/10090:Gtf2f2 ^@ http://purl.uniprot.org/uniprot/Q3UMJ4|||http://purl.uniprot.org/uniprot/Q8R0A0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIF beta subunit family.|||Heterodimer of an alpha and a beta subunit. Interacts with HTATSF1 and URI1 (By similarity). Interacts with GPBP1. Interacts with GTF2B (via N-terminus); this interaction is inhibited in presence of GTF2F1 (By similarity).|||Nucleus|||TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. http://togogenome.org/gene/10090:Ifna4 ^@ http://purl.uniprot.org/uniprot/P07351|||http://purl.uniprot.org/uniprot/Q540C2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.|||Secreted http://togogenome.org/gene/10090:Ptgdr2 ^@ http://purl.uniprot.org/uniprot/Q9Z2J6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice are fertile and grew normally. Ear-swelling responses induced by hapten-specific IgE are less pronounced in deficient mice, giving 35-55% of the responses of normal mice. The reduction in cutaneous responses is associated with decreased infiltration of lymphocytes, eosinophils, and basophils and decreased production of macrophage-derived chemokine and RANTES at inflammatory sites. In models of chronic contact hypersensitivity induced by repeated hapten application, CRTH2-deficient mice result in a reduction by approximately half of skin responses and low levels (63% of control) of serum IgE production.|||Phosphorylated.|||Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses (By similarity).|||The 329-DSEL-332 motif is involved in the recycling of PTGDR2 to the cell surface after agonist-induced internalization. This motif seems to be required for GRK2 and GPRK5/GRK5 to promote agonist-induced internalization (By similarity). Thr-346 is a major site for PKC-induced internalization of the receptor (By similarity). http://togogenome.org/gene/10090:Trim3 ^@ http://purl.uniprot.org/uniprot/Q3TDT0|||http://purl.uniprot.org/uniprot/Q9R1R2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays essential roles in neuronal functions such as regulation of neuronal plasticity, learning, and memory (PubMed:24086586, PubMed:26527743). In addition to its neuronal functions, participates in other biological processes such as innate immunity or cell cycle regulation (By similarity). Component of the cytoskeleton-associated recycling or transport complex in neurons, polyubiquitinates gamma-actin, thus regulating neuronal plasticity, learning, and memory (PubMed:26527743). Ubiquitinates postsynaptic scaffold GKAP, a neuronal substrate involved in synaptic remodeling and thereby modulates dendritic spine morphology (By similarity). Positively regulates motility of microtubule-dependent motor protein KIF21B (PubMed:24086586). Induces growth arrest via its RING-dependent E3 ligase activity and ubiquinates CDKN1A. Positively regulates TLR3-mediated signaling by mediating 'Lys-63'-linked polyubiquitination of TLR3 (PubMed:26527743). In turn, promotes the recognition and sorting of polyubiquitinated TLR3 by the ESCRT complexes (By similarity).|||Early endosome|||Forms homooligomers. Interacts with TRIM2; this interaction reduces TRIM2 activity (By similarity). Associates with myosin-Vb (MYO5B) and alpha-actinin-4 (ACTN4) (By similarity). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts with ZFYVE28/LST2 (By similarity). Interacts with KIF21B (PubMed:24086586).|||The interaction with MYO5B is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades.|||Trim3-knockout mice are viable, fertile and showed no obvious morphological abnormalities (PubMed:24086586). However, they display increased levels of gamma-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation (PubMed:26527743). In addition, they express lower levels of antiviral genes and show lower levels of inflammatory response following poly(I:C) but not lipopolysaccharide (LPS) stimulation (PubMed:32878999).|||dendrite|||trans-Golgi network http://togogenome.org/gene/10090:Or13n4 ^@ http://purl.uniprot.org/uniprot/Q920Z2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Crygs ^@ http://purl.uniprot.org/uniprot/O35486|||http://purl.uniprot.org/uniprot/Q3UPY3 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Monomer. http://togogenome.org/gene/10090:Vmn1r42 ^@ http://purl.uniprot.org/uniprot/Q05A83|||http://purl.uniprot.org/uniprot/Q8VBS7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Krit1 ^@ http://purl.uniprot.org/uniprot/Q6S5J6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At stage 9.5 dpc ubiquitously expressed, at 12.5 dpc expressed in structures of the CNS, especially in zones of the proliferative active ventricular zones of the brain and in the spinal cord. Expression increased in organs that were in the state of organ expansion like lung and liver. At 17.5 dpc, expression was strongly reduced in endoderm-derived tissues. In early postnatal development, strongly expressed in regions of ossification.|||Cell junction|||Cell membrane|||Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner (By similarity). Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels. May play a role in the regulation of macroautophagy through the down-regulation of the mTOR pathway (PubMed:26417067).|||Contains 4 ANK repeats that precede the FERM domain.|||Expressed in heart, brain, spleen, lung, thymus, kidney and testis. Isoform 2 was more frequently expressed in the thymus than isoform 1.|||Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminus FERM domain) with RAP1A (active GTP-bound form preferentially); the interaction does not induce the opening conformation of KRIT1. Interacts (via N-terminus NPXY motif) with ITGB1BP1; the interaction induces the opening conformation of KRIT1 and competes with ITGB1 for ITGB1BP1 interaction. Associates (via N-terminus and C-terminus regions) with microtubules; the interaction is inhibited in presence of ITGB1BP1 and active GTP-bound RAP1A. Interacts (via FERM domain) with RAP1B. Interacts with CDH5. Interacts with RAP1A (By similarity). Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1 (PubMed:19151727).|||The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2).|||The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a nudix box and low sequence similarity with nudix hydrolase domains. The N-terminus and the C-terminus part associate together via the NPAY binding motif and adopt a lose conformation that is disrupted by ITGB1BP1, but not by RAP1A.|||cytoskeleton http://togogenome.org/gene/10090:Mfap3l ^@ http://purl.uniprot.org/uniprot/Q9D3X9 ^@ Caution|||Function|||Subcellular Location Annotation ^@ A protein kinase activity has been reported however PROSITE, Pfam do not detect a protein kinase domain. Its enzyme activity is therefore unsure.|||Cell membrane|||Cytoplasm|||May participate in the nuclear signaling of EGFR and MAPK1/ERK2.|||Nucleus http://togogenome.org/gene/10090:Dusp29 ^@ http://purl.uniprot.org/uniprot/Q8BK84 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Deletion of the long non-coding RNA (lncRNA) H19 leads to a decreased DUSP29 expression in muscle (at protein level). Down-regulated in muscle of high-fat diets-induced glucose-intolerant mice (PubMed:30201684). Induced during neurogenic skeletal muscle atrophy (PubMed:32639872).|||Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues within the same substrate, with a preference for phosphotyrosine as a substrate (By similarity). Involved in the modulation of intracellular signaling cascades. In skeletal muscle regulates systemic glucose homeostasis by activating, AMPK, an energy sensor protein kinase (PubMed:30201684). Affects MAP kinase signaling though modulation of the MAPK1/2 cascade in skeletal muscle promoting muscle cell differentiation, development and atrophy (PubMed:32639872).|||Homodimer (By similarity). Interacts with PRKAA2 (PubMed:30201684).|||Nucleus|||Skeletal muscle, liver and adipose tissue.|||Up-regulated during muscle cell differentiation. http://togogenome.org/gene/10090:Hrg ^@ http://purl.uniprot.org/uniprot/Q9ESB3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in liver, blood plasma, serum and in platelets. Also present in fibrin clots, wound fluid from acute wounds and chronic leg ulcers.|||Interacts with THBS1 (via the TSP type I repeats); the interaction blocks the antiangiogenic effect of THBS1 with CD36. Interacts with HPSE; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts (via the HRR domain) with TMP1; the interaction partially mediates the antiangiogenic properties of HRG. Interacts with kappa and lambda light chains of IgG molecules. Interacts with ATP5F1A; the interaction occurs on the surface of T-cells and alters their cell morphology in concert with CONA. Binds IgG molecules containing kappa and lambda light chains and inhibits the formation of insoluble immunoglobulin complexes. Interacts with F12; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding to HRG, inhibits factor XII autoactivation and contact-initiated coagulation (By similarity). Interacts with PLG (via its Kringle domains); the interaction tethers PLG to the cell surface and enhances its activation. Interacts (via the HRR domain) with TPM1; the interaction appears to contribute to the antiangiogenic properties of the HRR domain (By similarity). Interacts with THBS2; the interaction blocks the antiangiogenic effect of THBS2 with CD36.|||N-glycosylated.|||Null mice are viable and fertile, but have enhanced coagulation resulting in decreased bleeding times. The observed enhanced platelet activation mediates the accelerated angiogenic switch. Also enhanced fibrinolysis. Animals are unprotected against Candida fungal infection. Also shows larger tumor volume in cancerous state, an excessive stimulation of tumor angiogenesis, a suppression of tumor immune respons and an increased tumor growth and metastatic spread.|||Plasma glycoprotein that binds a number of ligands such as heme, heparin, heparan sulfate, thrombospondin, plasminogen, and divalent metal ions. Binds heparin and heparin/glycosaminoglycans in a zinc-dependent manner. Binds heparan sulfate on the surface of liver, lung, kidney and heart endothelial cells. Binds to N-sulfated polysaccharide chains on the surface of liver endothelial cells. Inhibits rosette formation. Acts as an adapter protein and is implicated in regulating many processes such as immune complex and pathogen clearance, cell chemotaxis, cell adhesion, angiogenesis, coagulation and fibrinolysis. Mediates clearance of necrotic cells through enhancing the phagocytosis of necrotic cells in a heparan sulfate-dependent pathway. This process can be regulated by the presence of certain HRG ligands such as heparin and zinc ions. Binds to IgG subclasses of immunoglobins containing kappa and lambda light chains with different affinities regulating their clearance and inhibiting the formation of insoluble immune complexes. Tethers plasminogen to the cell surface. Binds T-cells and alters the cell morphology. Acts as a regulator of the vascular endothelial growth factor (VEGF) signaling pathway; inhibits endothelial cell motility by reducing VEGF-induced complex formation between PXN/paxillin and ILK/integrin-linked protein kinase and by promoting inhibition of VEGF-induced tyrosine phosphorylation of focal adhesion kinases and alpha-actinins in endothelial cells. Also plays a role in the regulation of tumor angiogenesis and tumor immune surveillance. Normalizes tumor vessels and promotes antitumor immunity by polarizing tumor-associated macrophages, leading to decreased tumor growth and metastasis (By similarity). Modulates angiogenesis by blocking the CD6-mediated antiangiongenic effect of thrombospondins, THBS1 and THBS2.|||Proteolytic cleavage produces several HRG fragments which are mostly disulfide-linked and, therefore, not released. Cleavage by plasmin is inhibited in the presence of heparin, zinc ions or in an acidic environment. Cleavage reduces binding of HRG to heparan sulfate, but enhances the ability of HRG to bind and tether plasminogen to the cell surface. On platelet activation, releases a 33 kDa antiangiogenic peptide which encompasses the HRR. Also cleaved in the C-terminal by plasmin (By similarity).|||Secreted|||The His-rich (HRR) region contains approximately 12 tandem internal repeats of the 5-residue G[H/P][H/P]PH consensus sequence. HRR binds heparan sulfate and possesses antiangiogenic, antibacterial and antifungal properties through binding Candida cells, and preferentially lysing the ergosterol-containing liposomes at low pH. The tandem repeats also bind divalent metal ions and heme.|||The cystatin domains can also bind heparan sulfate. Binding is enhanced in the presence of zinc ions (By similarity). http://togogenome.org/gene/10090:Or8b39 ^@ http://purl.uniprot.org/uniprot/Q9EQA6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ctsw ^@ http://purl.uniprot.org/uniprot/P56203|||http://purl.uniprot.org/uniprot/Q8C2M0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C1 family.|||Endoplasmic reticulum|||May have a specific function in the mechanism or regulation of T-cell cytolytic activity. http://togogenome.org/gene/10090:Ywhaq ^@ http://purl.uniprot.org/uniprot/A3KML3|||http://purl.uniprot.org/uniprot/P68254 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1 (By similarity).|||Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1.|||Belongs to the 14-3-3 family.|||Cytoplasm|||Homodimer (By similarity). Interacts with CDKN1B ('Thr-198' phosphorylated form); the interaction translocates CDKN1B to the cytoplasm. Interacts with SSH1 (By similarity). Interacts with GAB2. Interacts with RGS7 (phosphorylated form) (By similarity). Interacts with CDK16 (PubMed:9197417). Interacts with the 'Ser-241' phosphorylated form of PDPK1 (By similarity). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (By similarity). Interacts with SLITRK1 (By similarity). Interacts with RIPOR2 (By similarity). Interacts with INAVA; the interaction increases upon PRR (pattern recognition receptor) stimulation and is required for cellular signaling pathway activation and cytokine secretion (By similarity). Interacts with MARK2, MARK3 and MARK4 (By similarity). Interacts with MEFV (By similarity). http://togogenome.org/gene/10090:Ptpn21 ^@ http://purl.uniprot.org/uniprot/G5E8J4|||http://purl.uniprot.org/uniprot/Q4KML9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||cytoskeleton http://togogenome.org/gene/10090:Vmn2r23 ^@ http://purl.uniprot.org/uniprot/E9PXI5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Etl4 ^@ http://purl.uniprot.org/uniprot/A2AQ25 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed predominantly in the notochord and mesonephros during embryogenesis as well as in other areas such as the epithalamus sulcus, lens vesicle, inner retinal layer, heart, hepatic primordial surface, infundibulum, surface ectoderm, hind gut and limb bud mesenchyme. In adults, expressed in a range of tissues including the nucleus pulposus, corpus callosum, kidney, cardiac muscle, Sertoli cells and hair follicles.|||Interacts with CPNE4 (via VWFA domain) (PubMed:12522145).|||Mice display a kinky-tail phenotype in about half of homozygotes with defects in the nucleus pulposus and annulus fibrosus of intertebral disks. Shortening and curving of caudal vertebrae 20-25 is apparent by the age of 2 weeks.|||Required for normal development of intervertebral disks.|||centrosome http://togogenome.org/gene/10090:Ints12 ^@ http://purl.uniprot.org/uniprot/Q9D168 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 12 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Nucleus http://togogenome.org/gene/10090:Or13a18 ^@ http://purl.uniprot.org/uniprot/Q8VGJ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Brs3 ^@ http://purl.uniprot.org/uniprot/O54798 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with C6orf89.|||Role in sperm cell division, maturation, or function. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Lgmn ^@ http://purl.uniprot.org/uniprot/A2RTI3|||http://purl.uniprot.org/uniprot/O89017|||http://purl.uniprot.org/uniprot/Q3UE99 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autocatalytic processing at pH 4.|||Belongs to the peptidase C13 family.|||Detected in kidney proximal tubules (at protein level). Ubiquitous. Particularly abundant in kidney and placenta.|||Glycosylated.|||Has a strict specificity for hydrolysis of asparaginyl bonds (PubMed:24407422, PubMed:9742219, PubMed:9891971). Can also cleave aspartyl bonds slowly, especially under acidic conditions (PubMed:24407422, PubMed:9742219, PubMed:9891971). Involved in the processing of proteins for MHC class II antigen presentation in the lysosomal/endosomal system (By similarity). Also involved in MHC class I antigen presentation in cross-presenting dendritic cells by mediating cleavage and maturation of Perforin-2 (MPEG1), thereby promoting antigen translocation in the cytosol (PubMed:37347855). Required for normal lysosomal protein degradation in renal proximal tubules (PubMed:17350006, PubMed:21292981). Required for normal degradation of internalized EGFR (PubMed:21292981). Plays a role in the regulation of cell proliferation via its role in EGFR degradation (PubMed:21292981).|||Homodimer before autocatalytic removal of the propeptide (PubMed:24407422). Monomer after autocatalytic processing (PubMed:24407422). May interact with integrins (By similarity).|||In the zymogen form, the uncleaved propeptide blocks access to the active site.|||Inhibited by cystatin-C.|||Lysosome|||Young mice initially display no obvious phenotype, but fail to gain weight normally. Mutant mice display pale kidneys with abnormal proliferation of proximal tubule cells, proximal tubule hyperplasia and develop kidney interstitium fibrosis. After 6 months, mutant mice display a decreased glomerular filtration rate, increased plasma creatinine levels and proteinuria. Glomerular lysosomes do not show a generalized defect in protein catabolism. Instead they show defects in the degradation of a set of target proteins, including EGFR. http://togogenome.org/gene/10090:Gtsf1l ^@ http://purl.uniprot.org/uniprot/Q9CWD0 ^@ Similarity ^@ Belongs to the UPF0224 (FAM112) family. http://togogenome.org/gene/10090:Elk4 ^@ http://purl.uniprot.org/uniprot/P41158 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Interacts with SIRT7.|||Involved in both transcriptional activation and repression. Interaction with SIRT7 leads to recruitment and stabilization of SIRT7 at promoters, followed by deacetylation of histone H3 at 'Lys-18' (H3K18Ac) and subsequent transcription repression. Forms a ternary complex with the serum response factor (SRF). Requires DNA-bound SRF for ternary complex formation and makes extensive DNA contacts to the 5'side of SRF, but does not bind DNA autonomously (By similarity).|||Lung and liver.|||Nucleus http://togogenome.org/gene/10090:Galnt11 ^@ http://purl.uniprot.org/uniprot/Q921L8 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.0 dpc, present in the left-right organiser (LRO) node, with enrichment in crown cells compared to pit cells (at protein level).|||Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Golgi apparatus membrane|||Interacts with NOTCH1.|||Mainly expressed in kidney. Weakly expressed in other tissues.|||Polypeptide N-acetylgalactosaminyltransferase that catalyzes the initiation of protein O-linked glycosylation and is involved in left/right asymmetry by mediating O-glycosylation of NOTCH1. O-glycosylation of NOTCH1 promotes activation of NOTCH1, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). Polypeptide N-acetylgalactosaminyltransferases catalyze the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Displays the same enzyme activity toward MUC1, MUC4, and EA2 than GALNT1. Not involved in glycosylation of erythropoietin (EPO) (By similarity).|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Anxa13 ^@ http://purl.uniprot.org/uniprot/Q99JG3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Apical cell membrane|||Belongs to the annexin family.|||Binds to membranes enriched in phosphatidylserine or phosphatidylglycerol in a calcium-dependent manner. Half-maximal membrane binding requires about 60 uM calcium. Does not bind to membranes that lack phospholipids with an acidic headgroup.|||Cell membrane|||Cytoplasmic vesicle|||Detected on the tips of microvilli in small intestine (at protein level).|||Monomer and homodimer. http://togogenome.org/gene/10090:Klhl10 ^@ http://purl.uniprot.org/uniprot/Q9D5V2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Does not seem to associate with actin.|||Expressed in elongating and elongated spermatids (steps 9-16).|||Heterozygous males are completely infertile because of disrupted spermiogenesis characterized by asynchronous spermatid maturation, degeneration of late spermatids, sloughing of postmeiotic germ cells from the seminiferous epithelium, and marked reduction in the numbers of late spermatids.|||May be a substrate-specific adapter of a CUL3-based E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins during spermatogenesis. Required for male fertility.|||Self-associates (By similarity). Interacts with CUL3; indicative for the participation in an E3 ubiquitin ligase complex.|||Testis specific. http://togogenome.org/gene/10090:Aff4 ^@ http://purl.uniprot.org/uniprot/Q9ESC8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AF4 family.|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with ELL2; the interaction is direct and leads to stabilize ELL2 and prevent ELL2 ubiquitination and degradation (By similarity). Interacts with ELL3; the interaction is direct.|||Expressed throughout embryogenesis with maximum expression at 10.5 and 12.5 dpc.|||Highly expressed in testis by Sertoli cells, and at low levels in other tissues.|||Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression (By similarity).|||Mice are infertile with azoospermia. Spermatogenesis is arrested at the level of spermiogenesis.|||Nucleus http://togogenome.org/gene/10090:Zfp213 ^@ http://purl.uniprot.org/uniprot/E9QAW0|||http://purl.uniprot.org/uniprot/Q3UGD5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Tsnax ^@ http://purl.uniprot.org/uniprot/Q9QZE7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts in combination with TSN as an endonuclease involved in the activation of the RNA-induced silencing complex (RISC). Possible role in spermatogenesis (By similarity).|||Belongs to the translin family.|||Detected in heart, brain, lung, liver, kidney and testis.|||Golgi apparatus|||Nucleus|||Ring-shaped heterooctamer of six TSN and two TSNAX subunits. Interacts with GOLGA3, TSNAXIP1, SUN1 and AKAP9. Interacts with the homodimeric form of C1D following gamma-radiation. Interacts with TSN and C1D in a mutually exclusive manner (By similarity).|||Sumoylated with SUMO1.|||perinuclear region http://togogenome.org/gene/10090:Syt1 ^@ http://purl.uniprot.org/uniprot/H6RXZ1|||http://purl.uniprot.org/uniprot/P46096 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.|||Calcium sensor that participates in triggering neurotransmitter release at the synapse (PubMed:11242035). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (PubMed:7961887). It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca(2+)-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca(2+)-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes (By similarity).|||Cytoplasm|||Detected in the brain at 18 days post coitum (dpc) (at protein level). Expression increases after birth, with expression increasing till adulthood.|||Expressed in the brain and adrenal medulla (at protein level).|||Glycosylated.|||Homotetramer (Probable). Heterodimer; heterodimerizes with SYT2 in presence of calcium (By similarity). Interacts with SCAMP5 (By similarity). Interacts with STON2 (By similarity). Forms a complex with SV2B, syntaxin 1 and SNAP25 (PubMed:15466855). Interacts with SV2A, SV2B and SV2C (By similarity). Interacts with RIMS1 (By similarity). Interacts with PRRT2 (PubMed:27052163). Interacts with DNAJC5 in a phosphorylation-dependent manner (By similarity). Interacts (via N-terminus) with RAB3A (By similarity). Interacts with SYT12 (By similarity). Interacts with calmodulin (By similarity).|||May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone.|||The first C2 domain mediates Ca(2+)-dependent phospholipid binding.|||The second C2 domain mediates interaction with SV2A and probably with STN2.|||chromaffin granule membrane|||secretory vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Ifit3 ^@ http://purl.uniprot.org/uniprot/Q64345 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IFIT family.|||Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3 (By similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts (via N-terminus) with MAVS, TBK1, TRAF6 and RIGI (By similarity). Interacts with COPS5 (By similarity).|||Cytoplasm|||IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS-mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exhibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin-dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Up-regulates CDKN1A/p21 by down-regulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2 (By similarity).|||Induced by T.gondii infection in the testes and uterus.|||Mitochondrion http://togogenome.org/gene/10090:Timd4 ^@ http://purl.uniprot.org/uniprot/Q6U7R4 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.|||Belongs to the immunoglobulin superfamily. TIM family.|||Deletion mice maintained on methionine and choline-deficient diet exhibit significantly more obvious inflammation and severe lipid accumulation.|||Down-regulated in lymphotoxin deficient mice.|||Homodimer.|||Low expression of Timd4 is associated with lymphotoxin deficiency.|||Membrane|||Phosphatidylserine receptor that plays different role in immune response including phagocytosis of apoptotic cells and T-cell regulation (PubMed:17960135). Controls T-cell activation in a bimodal fashion, decreasing the activation of naive T-cells by inducing cell cycle arrest, while increasing proliferation of activated T-cells by activating AKT1 and ERK1/2 phosphorylations and subsequent signaling pathways. Also plays a role in efferocytosis which is the process by which apoptotic cells are removed by phagocytic cells (PubMed:18354194, PubMed:18367551). Mechanistically, promotes the engulfment of apoptotic cells or exogenous particles by securing them to phagocytes through direct binding to phosphatidylserine present on apoptotic cells, while other engulfment receptors such as MERTK efficiently recognize apoptotic cells and mediate their ingestion (By similarity). Additionally, promotes autophagy process by suppressing NLRP3 inflammasome activity via activation of STK11/PRKAA1 pathway in a phosphatidylserine-dependent mechanism (PubMed:31263038).|||Predominantly expressed in lymphoid tissues, such as spleen, lymph nodes, and Peyer patches. Also expressed in fetal liver, salivary gland, and spleen stromal cells, predominantly in the marginal zone and to a lesser extent throughout the white pulp. Not expressed in bone marrow-derived cells. Expressed mainly by antigen presenting cells (APCs) in T- and B-cell areas, but not by T- or B-lymphocytes. http://togogenome.org/gene/10090:Pdzd7 ^@ http://purl.uniprot.org/uniprot/E9Q9W7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in adult cochlea and retina.|||Expressed in adult cochlea but not in developing cochlea or retina.|||Expressed in developing and adult cochlea and retina.|||Expressed in developing and adult cochlea but not retina.|||Expressed in retina and developing cochlea but not adult cochlea.|||Homodimerizes (via PDZ2 domain) (PubMed:25406310). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN (PubMed:25406310). Interacts (via PDZ domains) with WHRN; the interaction is direct (PubMed:25406310). Interacts with USH1G (By similarity). Interacts with ADGRV1 (via the cytoplasmic region) (PubMed:24962568, PubMed:23055499). Interacts with USH2A (via the cytoplasmic region) (PubMed:23055499). Interacts with MYO7A (via MyTH4-FERM domains) (PubMed:27525485).|||In cochlea hair cells, only isoforms 1, 2 and 4 are expressed at P5. At P24, isoforms 1, 2, 3 and 5 are expressed.|||In cochlear developing hair cells, essential in organizing the USH2 complex at stereocilia ankle links (PubMed:24334608). Blocks inhibition of adenylate cyclase activity mediated by ADGRV1 (PubMed:24962568).|||Isoform 1 is expressed in developing and adult cochlea but not retina (PubMed:24334608). Isoform 2 is expressed in developing and adult cochlea and retina (PubMed:24334608). Isoform 3 is expressed in adult cochlea and retina (PubMed:24334608). Isoform 4 is expressed in retina and developing cochlea but not adult cochlea (PubMed:24334608). Isoform 5 is expressed in adult cochlea but not in developing cochlea or retina (PubMed:24334608).|||Mutant mice exhibit congenital profound deafness and normal vestibular function. They show disorganized stereocilia bundles with a reduction in mechanotransduction currents and sensitivity in cochlear outer cells (PubMed:24334608). Knockout mice have normal vision function from rod and cone photoreceptors (PubMed:24334608).|||Nucleus|||cilium|||stereocilium http://togogenome.org/gene/10090:Fech ^@ http://purl.uniprot.org/uniprot/P22315|||http://purl.uniprot.org/uniprot/Q4QRK2 ^@ Activity Regulation|||Cofactor|||Disease Annotation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ferrochelatase family.|||Binds 1 [2Fe-2S] cluster.|||Catalyzes the ferrous insertion into protoporphyrin IX.|||Defects in Fech are the cause of a viable autosomal recessive mutation (named Fechm1Pas or Fch) that causes jaundice and anemia.|||During erythroid differentiation.|||Erythroid and hepatic cells.|||Homodimer (By similarity). Interaction with PGRMC1; the interaction results in decreased FECH activity (PubMed:27599036). Interacts with ABCB10 and SLC25A37; this interaction forms an oligomeric complex (PubMed:20427704). Forms a complex with ABCB7 and ABCB10, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). Interacts with ABCB7 and ABCB10 (PubMed:30765471).|||Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Exog ^@ http://purl.uniprot.org/uniprot/Q8C163 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA/RNA non-specific endonuclease family.|||Endo/exonuclease with nicking activity towards supercoiled DNA, a preference for single-stranded DNA and 5'-3' exonuclease activity.|||Homodimer.|||Mitochondrion inner membrane|||The active site contains 1 hydrated divalent metal cation that has only 1 direct interaction with the protein; all other interactions are via water molecules. http://togogenome.org/gene/10090:Myl1 ^@ http://purl.uniprot.org/uniprot/P05977 ^@ Function|||PTM|||Subunit ^@ Isoform MLC3 is acetylated at position 2.|||Myosin is a hexamer of 2 heavy chains and 4 light chains. Does not bind calcium.|||Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function. http://togogenome.org/gene/10090:Pcbp1 ^@ http://purl.uniprot.org/uniprot/P60335 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation ^@ Cytoplasm|||Embryonic lethality in the peri-implantation stage (between dpc 4.5 and dpc 8.5) (PubMed:26527618). Conditional deletion in the erythroid lineage is not lethal and does not lead to defects in the hematopoietic pathway (PubMed:34180713). Mice lacking Pcbp1 and Pcbp2 in the erythroid lineage die at midgestation; lethality is caused by impaired erythroid development and loss of blood formation (PubMed:34180713).|||Nucleus|||Phosphorylated; lowers poly(rC)-binding activity.|||Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (By similarity). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (PubMed:34180713). http://togogenome.org/gene/10090:Mbp ^@ http://purl.uniprot.org/uniprot/P04370|||http://purl.uniprot.org/uniprot/Q3UGF3|||http://purl.uniprot.org/uniprot/Q542T4|||http://purl.uniprot.org/uniprot/Q5D096 ^@ Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As in other animals, several charge isomers may be produced as a result of optional post-translational modifications, such as phosphorylation of serine or threonine residues, deamidation of glutamine or asparagine residues, citrullination and methylation of arginine residues.|||Belongs to the myelin basic protein family.|||Cytoplasm|||Defects in Mbp are a cause of dysmyelinating diseases such as the shiverer (SHI) and myelin deficient (MLD) diseases characterized by decreased myelination in the CNS, tremors, and convulsions of progressively increasing severity leading to early death. The shiverer mice only express isoform 2, the MLD mice have a reduced amount of Mbp.|||Homodimer.|||In the embryo, isoform 1-isoform 3 are found in neurons within the central nervous system (primarily in pioneer neurons important in the formation of the cortex) and the peripheral nervous system. They are also expressed in the thymus, gut, lung and kidney. In the adult, isoform 1-isoform 3 are highly expressed in the brain (mainly in brain regions rich in oligodendrocytes) and spleen. Lower levels are seen in the heart, kidney and lung. Isoform 2 is also found in cells of the immune system. The isoforms missing the 134 first amino acids (isoform 4-isoform 13) are almost exclusively produced in the myelin-forming cells, the mature oligodendrocytes.|||Methylated on arginine residues; decreases with the age of the animal, making MBP more cationic.|||Myelin membrane|||Nucleus|||Phosphorylated by TAOK2, VRK2, MAPK11, MAPK12, MAPK14 and MINK1.|||Proteolytically cleaved in B cell lysosomes by cathepsin CTSG which degrades the major immunogenic MBP epitope and prevents the activation of MBP-specific autoreactive T cells.|||The classic group of MBP isoforms (isoform 4-isoform 13) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined to optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function.|||The differential expression of MBP isoforms is developmentally regulated. Isoform 2 and isoform 3 are first expressed during embryonic stages (as early as at embryonic day 11.5), expression of isoform 1 is turned on shortly after birth. Expression of the isoforms missing the 134 first amino acids occurs later, presumably as the oligodendrocytes approach their terminally differentiated state. http://togogenome.org/gene/10090:Hmx1 ^@ http://purl.uniprot.org/uniprot/O70218 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HMX homeobox family.|||DNA-binding protein that binds to the 5'-CAAG-3' core sequence. May function as a transcriptional repressor. Seems to act as a transcriptional antagonist of NKX2-5. May play an important role in the development of craniofacial structures such as the eye and ear.|||Expressed in neural crest-derived tissues, including, nerve ganglia and cranial mesenchyme.|||Nucleus|||On 9.5 dpc expressed in the trigeminal (V) ganglion. On 10.5-11 dpc, expressed in the eye, second branchial arch and the dorsal root ganglion. On 11.5-12 dpc, expressed in the lens and neural epithelium of the eye. On 14-16 dpc, expressed in the sympathetic ganglon and dorso-lateral mesenchyme near the developing ear. http://togogenome.org/gene/10090:Tmem200c ^@ http://purl.uniprot.org/uniprot/J3QK46 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM200 family.|||Membrane http://togogenome.org/gene/10090:Lhx2 ^@ http://purl.uniprot.org/uniprot/F6Z9H5|||http://purl.uniprot.org/uniprot/Q543C6|||http://purl.uniprot.org/uniprot/Q9Z0S2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional activator. Stimulates the promoter of the alpha-glycoprotein gene. Transcriptional regulatory protein involved in the control of cell differentiation in developing lymphoid and neural cell types.|||Interacts (via LIM domains) with CITED2 (PubMed:10593900). Interacts with POU4F2 isoform 1 (PubMed:24643061).|||LIM domains are necessary for transcription activation.|||Nucleus http://togogenome.org/gene/10090:Bace2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0I8|||http://purl.uniprot.org/uniprot/Q9JL18 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase A1 family.|||Cell membrane|||Endoplasmic reticulum|||Endosome|||Glycosylated.|||Golgi apparatus|||High expression in pancreatic islets. Expressed at much lower levels in the pituitary, colon, and ovaries and is nearly absent from all the other tissues.|||Melanosome|||Membrane|||Monomer. Interacts with RTN3 and RTN4.|||Mutant mice display silvery coat color. This is associated with abnormal melanosome morphology and melanin deposits, likely due to deficient PMEL processing and amyloid fibril formation.|||Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672. Involved in the proteolytic shedding of PMEL at early stages of melanosome biogenesis. Cleaves PMEL within the M-beta fragment to release the amyloidogenic PMEL luminal fragment containing M-alpha and a small portion of M-beta N-terminus. This is a prerequisite step for subsequent processing and assembly of PMEL fibrils into amyloid sheets. Responsible also for the proteolytic processing of CLTRN in pancreatic beta cells.|||Undergoes autoproteolytic cleavage. http://togogenome.org/gene/10090:Bves ^@ http://purl.uniprot.org/uniprot/Q9ES83 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the popeye family.|||Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity. Involved in the formation and regulation of the tight junction (TJ) paracellular permeability barrier in epithelial cells (PubMed:16188940). Plays a role in VAMP3-mediated vesicular transport and recycling of different receptor molecules through its interaction with VAMP3 (PubMed:20057356). Plays a role in the regulation of cell shape and movement by modulating the Rho-family GTPase activity through its interaction with ARHGEF25/GEFT (PubMed:18541910). Induces primordial adhesive contact and aggregation of epithelial cells in a Ca(2+)-independent manner. Also involved in striated muscle regeneration and repair and in the regulation of cell spreading (PubMed:11839816). Important for the maintenance of cardiac function. Plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding and, probably, by increasing cell surface expression of the potassium channel KCNK2 and enhancing current density (PubMed:26642364). Is a caveolae-associated protein important for the preservation of caveolae structural and functional integrity as well as for heart protection against ischemia injury (PubMed:24066022).|||Expressed in epithelial cells, skeletal muscle, heart and intestinal smooth muscle (at protein level). Expressed in fetal and adult heart and skeletal muscle.|||Expressed in the mesoderm of the cardiac crescent at 9.5 dpc. Expressed in cardiac myocytes of the sinoatrial compartment and some restricted areas of the dorsal part of the ventricle chambers at 10.5 dpc and 12.5 dpc. Expressed in branchial arches, myotome and in a posterior domain in the limb at 10.5 dpc. Expressed in the heart, mainly in the compact layer myocardium, peridigital mesenchyme, the somites of the tail bud, the smooth muscle cells of the trachea and the developing bronchial tree, the smooth muscle cells lining the digestive tract, the dorsal root ganglia and the pancreas anlage at 13.5 dpc (at protein level). Expressed in the sinoatrial compartment and some restricted areas in the dorsal part of the ventricle at 9.5 dpc, 10.5 dpc and 11.5 dpc. At 12.5 dpc, expression was observed in the ventral half of the ventricle where it was limited to the subepicardial compact layer.|||Homodimer. Homodimerization requires the C-terminus cytoplasmic region (By similarity). Interacts (via the C-terminus cytoplasmic tail) with TJP1. Interacts (via the C-terminus cytoplasmic tail) with ARHGEF25/GEFT (via the DH domain). Interacts (via the C-terminus cytoplasmic tail) with VAMP3. Interacts with KCNK2; the interaction enhances KCNK2 surface expression and is inhibited by cAMP (PubMed:22354168, PubMed:26642364). Interacts with CAV3 (PubMed:24066022).|||Lateral cell membrane|||Membrane|||Skeletal muscle regeneration appears to be less efficient and delayed (PubMed:11839816). Knockout mice are deficient to adapt heart rate to physiological stress, this deficiency develops in older mice. They show severe sinus node dysfunction with long pauses and intercurrent periods of normal synus rhythm. The sinus node structure is abnormal with a loss of pacemaker tissue from the inferior part of the sinus node and a compact structure of the superior sinus node (PubMed:22354168). They have inpaired functional recovery after ischemia/reperfusion injury (PubMed:24066022).|||caveola|||sarcolemma|||tight junction http://togogenome.org/gene/10090:Zpld1 ^@ http://purl.uniprot.org/uniprot/Q8BGZ8 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Cytoplasmic vesicle membrane|||Glycoprotein which is a component of the gelatinous extracellular matrix in the cupulae of the vestibular organ.|||Proteolytically cleaved before the transmembrane segment to yield the secreted form found in the extracellular matrix of the cupula.|||extracellular matrix http://togogenome.org/gene/10090:Naa60 ^@ http://purl.uniprot.org/uniprot/H3BIY0|||http://purl.uniprot.org/uniprot/H3BJZ6|||http://purl.uniprot.org/uniprot/Q9DBU2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated: autoacetylation is required for optimal acetyltransferase activity.|||Belongs to the acetyltransferase family. NAA60 subfamily.|||Golgi apparatus membrane|||Monomer and homodimer; monomer in presence of substrate and homodimer in its absence.|||N-alpha-acetyltransferase that specifically mediates the acetylation of N-terminal residues of the transmembrane proteins, with a strong preference for N-termini facing the cytosol. Displays N-terminal acetyltransferase activity towards a range of N-terminal sequences including those starting with Met-Lys, Met-Val, Met-Ala and Met-Met. Required for normal chromosomal segregation during anaphase. May also show histone acetyltransferase activity; such results are however unclear in vivo and would require additional experimental evidences. http://togogenome.org/gene/10090:Eif4a3 ^@ http://purl.uniprot.org/uniprot/Q91VC3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent RNA helicase. Involved in pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms; the function is different from the established EJC assembly. Involved in craniofacial development.|||Belongs to the DEAD box helicase family. eIF4A subfamily.|||Cytoplasm|||Identified in the spliceosome C complex. Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4. May interact with NOM1. Interacts with POLDIP3. Interacts with CWC22 and PRPF19 in an RNA-independent manner. Direct interaction with CWC22 is mediated by the helicase C-terminal domain. Full interaction with CWC22 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro). Interacts with NCBP3 (By similarity). Interacts with NRDE2 (By similarity). Interacts with DHX34; the interaction is RNA-independent (By similarity).|||Nucleus|||Nucleus speckle|||The ATPase activity is increased some 4-fold in the presence of RNA. http://togogenome.org/gene/10090:Tst ^@ http://purl.uniprot.org/uniprot/P52196 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue (By similarity).|||Expressed in numerous tissues.|||Mitochondrion matrix|||Monomer.|||Together with MRPL18, acts as a mitochondrial import factor for the cytosolic 5S rRNA. Only the nascent unfolded cytoplasmic form is able to bind to the 5S rRNA (By similarity). Formation of iron-sulfur complexes and cyanide detoxification. http://togogenome.org/gene/10090:Rgs2 ^@ http://purl.uniprot.org/uniprot/O08849 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in a wide variety of tissues.|||Interacts with GNAQ. Does not interact with GNAI1 and GNAI3. Interacts with EIF2B5. Interacts with PRKG1 (isoform alpha).|||Mutant mice display increased blood pressure and impaired relaxation of vascular smooth muscle.|||Phosphorylated by protein kinase C. Phosphorylation by PRKG1 leads to activation of RGS2 activity.|||Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (By similarity). It is involved in the negative regulation of the angiotensin-activated signaling pathway (By similarity). Plays a role in the regulation of blood pressure in response to signaling via G protein-coupled receptors and GNAQ. Plays a role in regulating the constriction and relaxation of vascular smooth muscle (PubMed:14608379). Binds EIF2B5 and blocks its activity, thereby inhibiting the translation of mRNA into protein (By similarity).|||nucleolus http://togogenome.org/gene/10090:C7 ^@ http://purl.uniprot.org/uniprot/D3YXF5 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the complement C6/C7/C8/C9 family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Fhl5 ^@ http://purl.uniprot.org/uniprot/Q9WTX7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with CREM (via the third LIM domain) (PubMed:10086359). Interacts (via second LIM domain) with SPAG8 (PubMed:20488182).|||May be involved in the regulation of spermatogenesis. Stimulates CREM transcriptional activity in a phosphorylation-independent manner (By similarity).|||Nucleus|||Testis-specific, temporal expression is coordinated with CREM. http://togogenome.org/gene/10090:Prmt3 ^@ http://purl.uniprot.org/uniprot/Q922H1 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.|||Cytoplasm|||Inhibited by N-ethylmaleimide and high concentrations of zinc chloride.|||Monomer and homodimer (By similarity). Interacts with EPB41L3 (via FERM domain); the interaction is direct and inhibits the protein-arginine N-methyltransferase activity of PRMT3. Interacts with the 40S ribosomal protein RPS2. Interacts with ALDH1A1; the interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity and is independent of the methyltransferase activity of PRMT3 (By similarity).|||Protein-arginine N-methyltransferase that catalyzes both the monomethylation and asymmetric dimethylation of the guanidino nitrogens of arginine residues in target proteins, and therefore falls into the group of type I methyltransferases (By similarity). May regulate retinoic acid synthesis and signaling by inhibiting ALDH1A1 retinal dehydrogenase activity (By similarity).|||The C2H2-type zinc-finger is responsible for substrate specificity. http://togogenome.org/gene/10090:Tsen15 ^@ http://purl.uniprot.org/uniprot/G3X8S8|||http://purl.uniprot.org/uniprot/Q8R3W5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although only weakly related to the S.cerevisiae SEN15 protein, it probably displays the same function within the tRNA splicing endonuclease complex.|||Belongs to the SEN15 family.|||Homodimer. tRNA splicing endonuclease is a heterotetramer composed of TSEN2, TSEN15, TSEN34/LENG5 and TSEN54. tRNA splicing endonuclease complex also contains proteins of the pre-mRNA 3' end processing machinery such as CLP1, CPSF1, CPSF4 and CSTF2 (By similarity).|||Non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5' and 3' splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Hdac2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J008|||http://purl.uniprot.org/uniprot/P70288 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone deacetylase family. HD Type 1 subfamily.|||Belongs to the histone deacetylase family. HD type 1 subfamily.|||Cytoplasm|||Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:18754010). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:18754010). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:18754010). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR (By similarity). Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:17707228). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity). Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity (By similarity). May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (PubMed:15226430). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A (PubMed:20071335). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:30279482).|||Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.|||Nucleus|||Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7, the core complex associates with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex (By similarity). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:27806305). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:27806305). Component of a RCOR/GFI/KDM1A/HDAC complex (PubMed:17707228). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A (By similarity). The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (By similarity). Part of a complex containing the core histones H2A, H2B, H3 and H4, DEK and unphosphorylated DAXX (By similarity). Part of a complex containing ATR and CHD4 (By similarity). Forms a heterologous complex at least with YY1 (By similarity). Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1 (By similarity). Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2 (By similarity). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 (By similarity). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2 (By similarity). Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 (By similarity). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC1 (By similarity). Interacts directly with GFI1 (By similarity). Interacts directly with GFI1B (By similarity). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (By similarity). Interacts with ATR (By similarity). Interacts with BCL6 (non-acetylated form) (By similarity). Interacts with BEND3 (By similarity). Interacts with CBFA2T3 (PubMed:11533236). Interacts with CDK2AP1 (By similarity). Interacts with CHD4 (PubMed:27806305). Interacts with CHD5 (PubMed:27806305). Interacts with CHFR (By similarity). Interacts with CRY1 (PubMed:15226430). Interacts with DNMT1 (By similarity). Interacts with GATAD2A (By similarity). Interacts with HCFC1 (By similarity). Interacts with HDAC7 (PubMed:10984530). Interacts with HDAC10 (By similarity). Interacts with INSM1 (PubMed:24227653). Interacts with KDM4A (By similarity). Interacts with MACROH2A1 (via the non-histone region) (PubMed:16107708). Interacts with MBD3L2 (By similarity). Interacts with MTA1, with a preference for sumoylated MTA1 (By similarity). Interacts with NACC2 (By similarity). Interacts with NRIP1 (By similarity). Interacts with PELP1 (By similarity). Interacts with PIMREG (By similarity). Interacts with PRDM6 (PubMed:16537907). Interacts with PWWP2B (PubMed:34180153) Interacts with SAP30 (PubMed:9702189). Interacts with SAP30L (By similarity). Interacts with SETDB1 (PubMed:12398767). Interacts with SIX3 (PubMed:17666527). Interacts with SMARCAD1 (By similarity). Interacts with SNW1 (By similarity). Interacts with SPHK2 (By similarity). Interacts with SPEN/MINT (By similarity). Interacts (CK2 phosphorylated form) with SP3 (By similarity). Interacts with SUV39H1 (PubMed:11788710). Interacts with TSHZ3 (via its N-terminus) (By similarity). Interacts with ZMYND8 (By similarity). Interacts with ZNF431 (PubMed:21177534, PubMed:22391310). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). Identified in a complex with HDAC1, KCTD19, DNTTIP1 and ZNF541 (PubMed:34075040, PubMed:35341968).|||S-nitrosylated by GAPDH. In neurons, S-nitrosylation at Cys-262 and Cys-274 does not affect enzyme activity, but induces HDAC2 release from chromatin. This in turn increases acetylation of histones surrounding neurotrophin-dependent gene promoters and promotes their transcription. In embryonic cortical neurons, S-Nitrosylation regulates dendritic growth and branching.|||Was originally thought to be S-nitrosylated and to interact with MTA1 (PubMed:20519513). However, this work was later retracted (PubMed:28314777). Nevertheless, other publications demonstrate that it is S-nitrosylated and there are several publications in the human ortholog demonstrating its interaction with MTA1 (PubMed:18754010, PubMed:20972425). http://togogenome.org/gene/10090:Zfp609 ^@ http://purl.uniprot.org/uniprot/Q8BZ47 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated by ZNF608 (PubMed:23076336). Isoform 2 is up-regulated during neuronal differentiation (PubMed:25921068).|||Expressed in myoblasts (PubMed:28344082). Expressed in neurons in various brain regions, including striatum, prefrontal cortex, olfactory bulb, midbrain, cerebellum and hippocampus (PubMed:25921068). Expressed in neural stem cells (at protein level) (PubMed:28041881). Expressed in thymocytes (PubMed:23076336).|||Expressed in the developing brain at 12.5 dpc. At 14.5 dpc, becomes enriched in the ventricular zone and later, restricted to the progenitor population as cortical neurogenesis peaks. At this stage, not detected in the subventricular zone/intermediate zone (SVZ/IZ). At later stages, detected in the neurons of the cortical plate and in stem cells near the ventricular surface.|||Interacts (via N-terminus) with NIPBL (PubMed:28041881). Interacts with the multiprotein complex Integrator (PubMed:28041881).|||Involved in regulation of myoblast proliferation during myogenesis.|||Nucleus|||Produced by a back-splicing reaction which joins the 5'-splice site of the first coding exon with the 3'-splice site of the upstream intron resulting in a circular RNA, called circ-ZNF609. The translation starts with the same initiator methionine as that of the linear transcript encoding isoform 1. The stop codon is created upon circularization.|||Transcription factor, which activates RAG1, and possibly RAG2, transcription. Through the regulation of RAG1/2 expression, may regulate thymocyte maturation (PubMed:28344082). Along with NIPBL and the multiprotein complex Integrator, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (PubMed:28041881). http://togogenome.org/gene/10090:Tomm40 ^@ http://purl.uniprot.org/uniprot/Q9QYA2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tom40 family.|||Channel-forming protein essential for import of protein precursors into mitochondria. Plays a role in the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) by forming a complex with BCAP31 and mediating the translocation of Complex I components from the cytosol to the mitochondria.|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70). Interacts with mitochondrial targeting sequences. Interacts with TIMM29; linking the TIM22 complex to the TOM complex. Forms a complex with BCAP31 (via C-terminus) which mediates the translocation of components of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) from the cytosol to the mitochondria (By similarity). Interacts (via N-terminus) with CYP1A1 (via mitochondrial targeting signal); this interaction is required for CYP1A1 translocation across the mitochondrial outer membrane (By similarity).|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Gnl3l ^@ http://purl.uniprot.org/uniprot/Q6PGG6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class YlqF/YawG GTPase family.|||In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.|||Interacts with MDM2; this interaction, which occurs in the nucleoplasm, stabilizes MDM2. Indirectly interacts with TP53, via MDM2-binding. Interacts with TERF1; this interaction probably occurs in the nucleoplasm and is increased during mitosis, when the nucleolus is disassembled. This binding may promote TERF1 homodimerization. Interacts with TERT.|||Stabilizes TERF1 telomeric association by preventing TERF1 recruitment by PML. Stabilizes TERF1 protein by preventing its ubiquitination and hence proteasomal degradation. Does so by interfering with TERF1-binding to FBXO4 E3 ubiquitin-protein ligase. Required for cell proliferation. By stabilizing TRF1 protein during mitosis, promotes metaphase-to-anaphase transition. Stabilizes MDM2 protein by preventing its ubiquitination, and hence proteasomal degradation. By acting on MDM2, may affect TP53 activity. Required for normal processing of ribosomal pre-rRNA. Binds GTP (By similarity).|||nucleolus http://togogenome.org/gene/10090:Or8b55 ^@ http://purl.uniprot.org/uniprot/Q8VG50 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Limch1 ^@ http://purl.uniprot.org/uniprot/Q3UH68 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration.|||Belongs to the LIMCH1 family.|||Interacts with MYH9; independently of the integration of MYH9 into the myosin complex.|||stress fiber http://togogenome.org/gene/10090:Poll ^@ http://purl.uniprot.org/uniprot/Q9QXE2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-X family.|||DNA polymerase that functions in several pathways of DNA repair. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Also contributes to DNA double-strand break repair by non-homologous end joining and homologous recombination. Has both template-dependent and template-independent (terminal transferase) DNA polymerase activities. Has also a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.|||Interacts with PCNA. Interacts with PAXX; promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL. Interacts with XRCC4; promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL. Interacts with NHEJ1/XLF; promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL.|||Nucleus http://togogenome.org/gene/10090:Trpc1 ^@ http://purl.uniprot.org/uniprot/B2RPS7|||http://purl.uniprot.org/uniprot/B7ZMP6|||http://purl.uniprot.org/uniprot/Q61056 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activation of PRKCA induces phosphorylation of TRPC1 and subsequent Ca2+ entry into cells.|||Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC1 sub-subfamily.|||Homotetramer and heterotetramer with TRPC4 and/or TRPC5 (By similarity). Interacts with TRPC4 and TRPC5 (By similarity). Interacts with ITPR3 (By similarity). Interacts with MX1 and RNF24 (By similarity). Interacts with FKBP4 (By similarity). Interacts with TRPC4AP (PubMed:20458742). Interacts with PLSCR1 (PubMed:32110987).|||Membrane|||Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Seems to be also activated by intracellular calcium store depletion. http://togogenome.org/gene/10090:Vmn1r9 ^@ http://purl.uniprot.org/uniprot/A2RST7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ndor1 ^@ http://purl.uniprot.org/uniprot/A2AI05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NADPH-dependent diflavin oxidoreductase NDOR1 family.|||In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||In the N-terminal section; belongs to the flavodoxin family.|||Interacts with CIAPIN1; as part of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery (By similarity). Interacts with DCPS (By similarity).|||NADPH-dependent reductase which is a central component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery. Transfers electrons from NADPH via its FAD and FMN prosthetic groups to the [2Fe-2S] cluster of CIAPIN1, another key component of the CIA machinery. In turn, this reduced cluster provides electrons for assembly of cytosolic iron-sulfur cluster proteins. It can also reduce the [2Fe-2S] cluster of CISD1 and activate this protein implicated in Fe/S cluster repair (By similarity). In vitro can fully activate methionine synthase/MTR in the presence of soluble cytochrome b5/CYB5A (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Zscan20 ^@ http://purl.uniprot.org/uniprot/B2KFW1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Wfdc2 ^@ http://purl.uniprot.org/uniprot/Q9DAU7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Broad range protease inhibitor.|||Homotrimer; disulfide-linked.|||Secreted http://togogenome.org/gene/10090:Hap1 ^@ http://purl.uniprot.org/uniprot/O35668 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Depressed postnatal feeding behavior leading to premature death latest at P9. Degeneration in hypothalamic regions that control feeding behavior.|||Early endosome|||Endoplasmic reticulum|||Isoform A is phosphorylated on Thr-598.|||Lysosome|||Mitochondrion|||Nucleus|||Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB regulating the number of Npyr1-expressing cells), and ITPR1/InsP3R1-mediated Ca(2+) release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesiss; however, reports are conflicting: PubMed:21985783 reports that Hap1 is required for ciliogenesis in primary cortical neurons and proposes that HTT interacts with PCM1 through HAP1; PubMed:23532844 reports that mice with disrupted Hap1 display normal cilium formation and function. Involved in regulation of exocytosis. Isoform A but not isoform B seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP.|||Presynapse|||Self-associates. Interacts with HTT/huntingtin; enhanced by an expanded polyglutamine repeat within HTT. Isoform A interacts with DCTN1; decreased in presence of HTT with expanded polyglutamine repeat; decreased by phosphorylation of Hap1 isoform A at Thr-598. Isoform A interacts with KLC2; decreased by phosphorylation of Hap1 isoform A at Thr-598. Isoform A interacts with ITPR1 and APP. Isoform A interacts with AR; decreased by an expanded polyglutamine repeat within AR. Isoform A interacts with YWHAZ; enhanced by phosphorylation of Hap1 isoform A at Thr-598. Isoform A interacts with BDNF and SORT1; probably forming a complex involved in proBDNF trafficking, degradation and processing. Interacts with TBP, AHI1, HGS and KALRN. Interacts with KIF5A, KIF5B, KIF5C and GABRB3; indicative for an HAP1:KIF5 complex transporting a GABA(A) receptor as cargo. Interacts with ATXN3; in STBs. Interacts with NTRK2; HAP1 stabilizes association of NTRK2 with SORT1 preventing NTRK2 degradation. Interacts with CCDC113.|||autophagosome|||axon|||cytoskeleton|||dendrite|||dendritic spine|||growth cone|||neuron projection|||synaptic vesicle http://togogenome.org/gene/10090:Prss58 ^@ http://purl.uniprot.org/uniprot/Q8BW11 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Secreted|||Thr-195 is present instead of the conserved Ser which is expected to be an active site residue. It is therefore unsure if this protein has kept its catalytic activity. http://togogenome.org/gene/10090:Clec9a ^@ http://purl.uniprot.org/uniprot/Q8BRU4 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Deficient mice shown no alteration of dendritic cell phenotype and numbers and the response of dendritic cells to innate stimuli is not altered. No alterations are found in leukocyte numbers or frequencies in spleen, lymph node or thymus, and mice appear normal and do not develop any obvious symptoms of autoimmune disease.|||Functions as an endocytic receptor on a small subset of myeloid cells specialized for the uptake and processing of material from dead cells. Recognizes filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins, including spectrin, exposed when cell membranes are damaged, and mediate the cross-presentation of dead-cell associated antigens in a Syk-dependent manner.|||Isoform 1: Monomer. Isoform 4: Homodimer.|||Isoform 4 expressed at high levels by CD8(+) dendritic cells (DCs), and at low levels by plasmacytoid DCs but not by other hematopoietic cells.|||Membrane|||N-glycosylated.|||Not glycosylated. http://togogenome.org/gene/10090:Slc37a1 ^@ http://purl.uniprot.org/uniprot/Q8R070 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.|||Endoplasmic reticulum membrane|||Inhibited by vanadate but not by chlorogenic acid.|||Inorganic phosphate and glucose-6-phosphate antiporter. May transport cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocate inorganic phosphate into the opposite direction. Independent of a lumenal glucose-6-phosphatase. May not play a role in homeostatic regulation of blood glucose levels. http://togogenome.org/gene/10090:Gjd4 ^@ http://purl.uniprot.org/uniprot/A0A654ICD8|||http://purl.uniprot.org/uniprot/Q8BSD4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family.|||Belongs to the connexin family. Delta-type subfamily.|||Cell membrane|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Arhgap31 ^@ http://purl.uniprot.org/uniprot/A6X8Z5 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By serum (at protein level).|||Expressed at highest levels in heart and lung.|||Functions as a GTPase-activating protein (GAP) for RAC1 and CDC42. Required for cell spreading, polarized lamellipodia formation and cell migration.|||Interacts with ITSN1, which inhibits GAP activity. Interacts with PARVA. Interacts with GTP-loaded RHOU (By similarity).|||Phosphorylated on Thr-776 by GSK3; which reduces GAP activity.|||focal adhesion|||lamellipodium http://togogenome.org/gene/10090:Marchf6 ^@ http://purl.uniprot.org/uniprot/Q6ZQ89 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated, which results in proteasomal degradation.|||Belongs to the DOA10/MARCHF6 family.|||E3 ubiquitin-protein ligase that promotes 'Lys-48'-linked ubiquitination of target proteins, leading to their proteasomal degradation. Promotes ubiquitination of DIO2, leading to its degradation. Promotes ubiquitination of SQLE, leading to its degradation. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May cooperate with UBE2G1.|||Endoplasmic reticulum membrane|||Interacts with DIO2. Interacts with SQLE.|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Tecr ^@ http://purl.uniprot.org/uniprot/G3UWE1|||http://purl.uniprot.org/uniprot/Q9CY27 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the steroid 5-alpha reductase family.|||Endoplasmic reticulum membrane|||Glycosylated.|||Interacts with ELOVL1 and LASS2.|||Involved in both the production of very long-chain fatty acids for sphingolipid synthesis and the degradation of the sphingosine moiety in sphingolipids through the sphingosine 1-phosphate metabolic pathway (By similarity). Catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle (By similarity). This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle (By similarity). This enzyme reduces the trans-2,3-enoyl-CoA fatty acid intermediate to an acyl-CoA that can be further elongated by entering a new cycle of elongation (By similarity). Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators (By similarity). Catalyzes the saturation step of the sphingosine 1-phosphate metabolic pathway, the conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA (By similarity).|||Membrane http://togogenome.org/gene/10090:Or52n4b ^@ http://purl.uniprot.org/uniprot/Q7TRU8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cym ^@ http://purl.uniprot.org/uniprot/B7ZWD6 ^@ Similarity ^@ Belongs to the peptidase A1 family. http://togogenome.org/gene/10090:Or12e8 ^@ http://purl.uniprot.org/uniprot/Q8VGT7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gsto1 ^@ http://purl.uniprot.org/uniprot/O09131 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Omega family.|||Exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities. Has S-(phenacyl)glutathione reductase activity. Has also glutathione S-transferase activity. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA) and dimethylarsonic acid.|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Wdr81 ^@ http://purl.uniprot.org/uniprot/Q5ND34 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat WDR81 family.|||Brain-specific, conditional knockout mice are born at the expected Mendelian frequency, but most of them die a few hours after birth. If they show no overt brain morphological abnormalities, a neuronal accumulation of SQSTM1 in foci is observed.|||Early endosome membrane|||Expressed in brain, Purkinje cells of cerebellum, retinal photoreceptor cells and spinal cord (at protein level) (PubMed:23595742). In brain, specifically expressed by neuronal cells (at protein level). Detected in a wide range of tissues including intestine, adipose tissue, liver, pancreas, thymus, spleen, kidney, heart, eye, sciatic nerve, and testis (PubMed:21885617, PubMed:23595742, PubMed:28404643).|||Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport. It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome. May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (By similarity). May also be involved in maintenance of normal mitochondrial structure and organization (PubMed:23595742).|||Interacts with WDR91; involved in early to late endosome cargo transport. Interacts with BECN1; negatively regulates the PI3 kinase/PI3K activity associated with endosomal membranes. Interacts with SQSTM1; the interaction is direct and regulates the interaction of SQSTM1 with ubiquitinated proteins. Interacts with MAP1LC3C; recruits MAP1LC3C to ubiquitinated protein aggregates in the aggrephagy process.|||Late endosome membrane|||Lysosome membrane|||Mitochondrion|||autophagosome membrane|||cytosol http://togogenome.org/gene/10090:Bend5 ^@ http://purl.uniprot.org/uniprot/Q8C6D4 ^@ Domain|||Function ^@ Acts as a transcriptional repressor.|||The BEN domain mediates DNA-binding. http://togogenome.org/gene/10090:Spink13 ^@ http://purl.uniprot.org/uniprot/Q3UTS8 ^@ Function|||Subcellular Location Annotation ^@ May be a serine protease inhibitor (By similarity). Essential for sperm maturation and fertility. Inhibits sperm acrosome reaction, protecting sperm from premature reaction (By similarity).|||Secreted http://togogenome.org/gene/10090:Or8b48 ^@ http://purl.uniprot.org/uniprot/A0A1L1SSS5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pabpn1 ^@ http://purl.uniprot.org/uniprot/Q8CCS6 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine dimethylation is asymmetric and involves PRMT1 and PRMT3. It does not influence the RNA binding properties (By similarity).|||Cytoplasm|||Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product. Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and controls also the poly(A) tail length. Increases the affinity of poly(A) polymerase for RNA. Is also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking and nonsense-mediated decay (NMD) of mRNA. Cooperates with SKIP to synergistically activate E-box-mediated transcription through MYOD1 and may regulate the expression of muscle-specific genes. Binds to poly(A) and to poly(G) with high affinity. May protect the poly(A) tail from degradation. Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (By similarity).|||May be due to a competing donor splice site.|||Monomer and homooligomer. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Binds RNA as a monomer and oligomerizes when bound to poly(A). Interacts with PAPOLA, but only in presence of oligo(A) RNA. Interacts with NUDT21/CPSF5 and transportin. Associates in a ternary complex with CPSF4 and NS/NS1 and interaction with NS/NS1, blocks nuclear export of host cell mRNAs. Associates in a single complex with SKIP and MYOD1 and interacts with SKIP in differentiated myocytes. May interact with SETX (By similarity). Interacts (via RRM domain and C-terminal arginine-rich region) with ZFP36 (via hypophosphorylated form); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single-stranded poly(A) RNA-oligomer and in a p38-dependent-manner and may down-regulated RNA poly(A) polymerase activity (PubMed:22844456). Component of the poly(A) tail exosome targeting (PAXT) complex composed of PABPN1, ZFC3H1 and MTREX. Interacts with ZFC3H1 in a RNase-insensitive manner (By similarity). Interacts with FRG1 (By similarity).|||Nucleus|||Nucleus speckle|||The RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding.|||Ubiquitous. http://togogenome.org/gene/10090:Pgr ^@ http://purl.uniprot.org/uniprot/Q00175|||http://purl.uniprot.org/uniprot/Q8BW69 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Expression of isoform A and isoform B in mammary epithelial cells is temporally and spatially separated during normal mammary gland development. Isoform A and isoform B are expressed in the pituitary. Isoform A and isoform B are differentially expressed in the ovary and oviduct, and the level of expression is dependent on both the cell type and estrous cycle stage.|||Infertile. Inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development and an impairment in the induction of a sexual behavioral response (PubMed:8603049). In isoform A-defective mice less oocytes are produced, only a subset of implantation-specific uterine epithelial target genes is regulated, and an increased progesterone-dependent proliferative activity of isoform B in the uterine epithelium is observed. Isoform B-defective mice showed unaffected ovulation (PubMed:10976068).|||Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and represses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-294 by ERK1/2 MAPK. Interacts with PRMT2 (By similarity). Isoform A interacts with NCOR2. Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B (but not isoform A) interacts with KLF9.|||Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2.|||Nucleus|||Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation (By similarity).|||Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-82, Ser-163, Ser-191 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-163 and Ser-294, but not at Ser-191, is impaired during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1 (By similarity).|||Steroid hormone receptor involved in the regulation of eukaryotic gene expression which affects cellular proliferation and differentiation in target tissues.|||Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294 (By similarity).|||The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor.|||Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation.|||Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294 (By similarity). http://togogenome.org/gene/10090:Or10v1 ^@ http://purl.uniprot.org/uniprot/Q8VF55 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Drc7 ^@ http://purl.uniprot.org/uniprot/Q6V3W6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the testis and is weakly expressed in the brain, thymus, lung and ovary (PubMed:31961863). Expressed in ciliated cells (PubMed:17971504).|||Belongs to the DRC7 family.|||Component of the nexin-dynein regulatory complex (N-DRC) (By similarity). Interacts with TCTE1/DRC5 (PubMed:28630322, PubMed:31961863). Interacts with DRC3 and GAS8/DRC4 (PubMed:31961863).|||Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes (By similarity). Essential for male fertility, sperm head morphogenesis and sperm flagellum formation (PubMed:31961863). Not required for ciliogenesis in the brain and trachea (PubMed:31961863).|||Expressed in diplotene and pachytene spermytocytes, and in round and elongating spermatids (at protein level). Strongly expressed in spleen and testis, faintly expressed in kidney, ovary and thymus.|||Male mice were infertile due to their short immotile spermatozoa (PubMed:31961863). Axoneme formation and manchette removal are impaired in spermatids (PubMed:31961863). No morphological abnormalities seen in multicilia of ependymal and tracheal epithelia and cilia motility is not impaired in ependymal cilia (PubMed:31961863).|||cilium axoneme|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Ifngr1 ^@ http://purl.uniprot.org/uniprot/P15261 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II cytokine receptor family.|||Cell membrane|||Deletion mutants show shortened lifespan and enhanced intestinal tumorigenesis. These tumors exhibit increased inflammation (PubMed:27286456). Loss of STAT1 signaling pathway activation is also observed (PubMed:19889125). After viral infection such as junin virus, mice develop disseminated infection and severe disease (PubMed:20926559).|||Monomer. Heterodimer with IFNGR2, to form the IFNG receptor complex. Interacts with JAK1. Interacts (when phosphorylated) with STAT1 (By similarity). Interacts with SOCS1 (PubMed:15522878).|||Phosphorylated at Ser/Thr residues. Phosphorylation of Tyr-445 is required for IFNG receptor signal transduction. Influenza virus infection leads to phosphorylation in a CSNK1A1-dependent manner.|||Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (, PubMed:20926559, PubMed:27286456). Associates with transmembrane accessory factor IFNGR2 to form a functional receptor (PubMed:2530582, PubMed:2532365, PubMed:2137461, PubMed:2531896, PubMed:2530216). Upon ligand binding, the intracellular domain of IFNGR1 opens out to allow association of downstream signaling components JAK1 and JAK2. In turn, activated JAK1 phosphorylates IFNGR1 to form a docking site for STAT1. Subsequent phosphorylation of STAT1 leads to its dimerization, translocation to the nucleus, and stimulation of target gene transcription (PubMed:19889125). STAT3 can also be activated in a similar manner although activation seems weaker (PubMed:15284232). IFNGR1 intracellular domain phosphorylation also provides a docking site for SOCS1 that regulates the JAK-STAT pathway by competing with STAT1 binding to IFNGR1 (PubMed:15522878).|||Ubiquitinated after phosphorylation in a CSNK1A1-dependent manner, leading to the lysosome-dependent degradation. Proteasomally degraded through 'Lys-48'-mediated ubiquitination. Ubiquitination is necessary for efficient IFNGR1 signaling. http://togogenome.org/gene/10090:Cidea ^@ http://purl.uniprot.org/uniprot/O70302 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CIDE family.|||Expressed at 15 dpc in the interscapular region of the embryo, that could correspond to the developing brown adipose tissue. Expression continues in the interscapular region at 18 dpc and postnatally. In mammary glands, begins to be highly expressed at day 14.5 of pregnancy. Expression is maintained at high levels throughout lactation and declines during post-lactational involution.|||Highly expressed in brown adipose tissue and, at lower levels, in white adipose tissue (at protein level) (PubMed:12910269, PubMed:18509062). Undetectable in undifferentiated preadipocytes (PubMed:12910269, PubMed:18509062). Expressed in mammary gland during pregnancy and lactation, in epithelial cells, but not in the surrounding adipose tissue (PubMed:22245780). Secreted into milk via milk fat globules (PubMed:22245780).|||Homodimer (PubMed:26609809). Interacts with CIDEC (By similarity). Directly interacts with CEBPB (PubMed:22245780). Interacts with isoform CLSTN3beta of CLSTN3; inhibiting the lipid transferase activity of CIDEA (PubMed:36477540).|||Lipid droplet|||Lipid transferase that promotes unilocular lipid droplet formation by mediating lipid droplet fusion (PubMed:18509062, PubMed:22144693, PubMed:26609809, PubMed:36477540). Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage (PubMed:18509062, PubMed:22144693, PubMed:26609809). Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by promoting directional net neutral lipid transfer from the smaller to larger lipid droplets (PubMed:18509062, PubMed:22144693, PubMed:26609809). The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair and occurs at a lower rate than that promoted by CIDEC (PubMed:18509062, PubMed:22144693). May also act as a CEBPB coactivator in epithelial cells to control the expression of a subset of CEBPB downstream target genes, including ID2, IGF1, PRLR, SOCS1, SOCS3, XDH, but not casein (PubMed:22245780). By interacting with CEBPB, strengthens the association of CEBPB with the XDH promoter, increases histone acetylation and dissociates HDAC1 from the promoter (PubMed:22245780). When overexpressed, induces apoptosis; the physiological significance of its role in apoptosis is unclear (PubMed:9564035).|||Mutant animals appear normal and fertile and produce the expected Mendelian ratio of heterozygous and homozygous descendents. They are lean and resistant to diet-induced obesity and diabetes. They exhibit higher metabolic rate, lipolysis in brown adipose tissue and core body temperature when subjected to cold treatment. Mutant females are unable to properly feed their pups who die within 3 days postpartum due to severely reduced milk lipids.|||Nucleus|||The CIDE-N domain is involved in homodimerization which is crucial for its function in promoting lipid exchange and transfer.|||The amphipathic helix mediates embedding into the lipid droplet phospholipid monolayer, promoting phosphatidic acid-binding, thereby facilitating triacylglycerol transfer.|||Up-regulated under conditions that enhance triacylglycerol deposition, including rosiglitazone treatment and high-fat diet. This up-regulation is mediated by PPARG. http://togogenome.org/gene/10090:Hid1 ^@ http://purl.uniprot.org/uniprot/Q8R1F6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the hid-1 family.|||Cytoplasm|||Golgi apparatus membrane http://togogenome.org/gene/10090:Camp ^@ http://purl.uniprot.org/uniprot/P51437 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2.|||Antimicrobial protein that is an integral component of the innate immune system (By similarity). Binds to bacterial lipopolysaccharides (LPS) (By similarity).|||Belongs to the cathelicidin family.|||Expressed in granulocytes (at protein level) (PubMed:9148921). High expression in bone marrow and small intestine (PubMed:9148921, PubMed:8706928). Expressed in testis, spleen, stomach, and intestine (PubMed:9148921). Very low expression found in heart, lung and skeletal muscle (PubMed:9148921). No expression in brain, kidney or liver (PubMed:9148921).|||Expressed in the adult and in the embryo where it is detected at 12-18 dpc.|||Proteolytically cleaved by cathepsin CTSG.|||Secreted|||Vesicle http://togogenome.org/gene/10090:Ndufb8 ^@ http://purl.uniprot.org/uniprot/Q9D6J5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB8 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Dkk3 ^@ http://purl.uniprot.org/uniprot/Q9QUN9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity).|||Belongs to the dickkopf family.|||Expressed in the developing cochlea.|||Highest expression in brain, eye and heart.|||Interacts with LRP5 and LRP6.|||Secreted|||The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6. http://togogenome.org/gene/10090:Zdhhc15 ^@ http://purl.uniprot.org/uniprot/Q8BGJ0 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autopalmitoylated (in vitro).|||Belongs to the DHHC palmitoyltransferase family.|||Expressed mainly in brain.|||Golgi apparatus membrane|||Inhibited by 2-bromopalmitate.|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates (PubMed:15603741, PubMed:17012030, PubMed:28167757). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable). Palmitoylates IGF2R and SORT1, promoting their partitioning to an endosomal membrane subdomain where they can interact with the retromer cargo-selective complex (By similarity). Thereby, regulates retrograde transport from endosomes to the Golgi apparatus of these lysosomal sorting receptors and plays a role in trafficking of lysosomal proteins (By similarity). In the nervous system, catalyzes the palmitoylation of DLG4/PSD95 and regulates its synaptic clustering and function in synaptogenesis (PubMed:15603741). Could be involved in the differentiation of dopaminergic neurons and the development of the diencephalon (By similarity). Could also catalyze the palmitoylation of GAP43 (PubMed:15603741, PubMed:17012030). Could also palmitoylate DNAJC5 and regulate its localization to the Golgi membrane (PubMed:18596047). Could also palmitoylate FYN as shown in vitro (By similarity).|||Postsynaptic density|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Dnaaf2 ^@ http://purl.uniprot.org/uniprot/Q8BPI1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIH1 family. Kintoun subfamily.|||Cytoplasm|||Dynein axonemal particle|||Expressed in nearly all organs of adult, with higher expression in tissues known to have motile cilia and flagella, such as brain and testis.|||Interacts with DNAI2 and HSPA1A (PubMed:19052621). Interacts with CFAP300. Interacts with DNAAF4. Interacts with DNAAF6/PIH1D3 (By similarity).|||Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment. http://togogenome.org/gene/10090:Yipf6 ^@ http://purl.uniprot.org/uniprot/Q8BR70 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the YIP1 family.|||Golgi apparatus membrane|||May be required for stable YIPF1 and YIPF2 protein expression.|||Predominantly interacts with YIPF1 or YIPF2, but may also form a ternary complex with YIPF1 and YIPF2. This interaction may stabilize YIPF1 and YIPF2. http://togogenome.org/gene/10090:Tax1bp3 ^@ http://purl.uniprot.org/uniprot/Q9DBG9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts (via its PDZ domain) with GLS2. Interacts (via its PDZ domain) with RTKN (via the C-terminal region); this interaction facilitates Rho-mediated activation of the FOS serum response element (SRE). Interacts (via PDZ domain) with ARHGEF16. Interacts (via PDZ domain) with KCNJ4 (via C-terminus). Competes with LIN7A for KCNJ4 binding (By similarity). Interacts (via its PDZ domain) with CTNNB1; this interaction inhibits the transcriptional activity of CTNNB1. Interacts with ADGRB2 (By similarity).|||May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway (By similarity).|||Nucleus http://togogenome.org/gene/10090:Srarp ^@ http://purl.uniprot.org/uniprot/Q3ULG3 ^@ Function|||Subunit ^@ Interacts with 14-3-3 proteins.|||May regulate the transcriptional function of androgen and estrogen receptors. http://togogenome.org/gene/10090:Nfatc2 ^@ http://purl.uniprot.org/uniprot/Q60591 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chimeric cDNA fused with Phyhd1 (Lrrc8a).|||Cytoplasm|||Expressed in the developing heart at 13.5 and 16.5 dpc, during the transition from spongy to compact myocardium (PubMed:17198697). Not detected in the skeletal system at 11 and 13.5 dpc (PubMed:10620601).|||Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas (PubMed:18675896). Expressed in cartilage (PubMed:10620601).|||In resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-365 region. Upon cell stimulation, all these sites except Ser-245 are dephosphorylated by calcineurin. Dephosphorylation induces a conformational change that simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, one site among Ser-53; Ser-54 and Ser-56 is phosphorylated; which is required for full transcriptional activity.|||Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other members such as NFATC4, NFATC3 or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex. The phosphorylated form specifically interacts with XPO1; which mediates nuclear export. NFATC proteins bind to DNA as monomers. Interacts with NFATC2IP. Interacts with FOXP3 (By similarity). Interacts with TBX21 ('Thr-302' phosphorylated form) (PubMed:23616576). Interacts with KAT2A (PubMed:28424240). Interacts with HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC2 dephosphorylation and activation (By similarity). Interacts with protein phosphatase PPP3CA/calcineurin A (By similarity).|||NFATC2-knocked down adult animals develop progressive difficulty in ambulation, fixed joint contractures and reduced joint motion, associated with joint destruction and the formation of ectopic cartilage and bone masses. Skeletal morphogenesis is normal during embryonic development. Cartilage cells from NFATC2-knocked down mice display uncontrolled growth consistent with malignant transformation.|||Nucleus|||Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway (By similarity). Is involved in the negative regulation of chondrogenesis (PubMed:10620601).|||PubMed:8668213 (AAC52929) sequence is a chimeric cDNA.|||Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.|||Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Hoxb7 ^@ http://purl.uniprot.org/uniprot/P09024 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Antp homeobox family.|||Forms a DNA-binding heterodimer with transcription factor PBX1.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Pabpc2 ^@ http://purl.uniprot.org/uniprot/Q62029 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the polyadenylate-binding protein type-1 family.|||Binds the poly(A) tail of mRNA.|||Cytoplasm http://togogenome.org/gene/10090:Ccdc190 ^@ http://purl.uniprot.org/uniprot/Q3URK1 ^@ Caution ^@ It is uncertain whether Met-1 or Met-5 is the initiator. http://togogenome.org/gene/10090:Ckmt2 ^@ http://purl.uniprot.org/uniprot/Q6P8J7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP:guanido phosphotransferase family.|||Exists as an octamer composed of four CKMT2 homodimers.|||Mitochondrial creatine kinase binds cardiolipin.|||Mitochondrion inner membrane|||Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (By similarity). http://togogenome.org/gene/10090:Gm21638 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Gm20896 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1|||http://purl.uniprot.org/uniprot/A0A087WSR0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Ino80c ^@ http://purl.uniprot.org/uniprot/Q8BHA0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity).|||Nucleus|||Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. http://togogenome.org/gene/10090:Obp1b ^@ http://purl.uniprot.org/uniprot/A2AEP0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Binds the chemical odorant 2-isobutyl-3-methoxypyrazine.|||Expressed in nasal mucosa (at protein level) (PubMed:8529023). Specifically detected in septal and lateral nasal glands (PubMed:9661663).|||May form a heterodimer with OBP1A.|||Secreted|||The N-terminus may be blocked. http://togogenome.org/gene/10090:Zfp646 ^@ http://purl.uniprot.org/uniprot/Q6NV66 ^@ Function|||Similarity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation. http://togogenome.org/gene/10090:Abcg5 ^@ http://purl.uniprot.org/uniprot/Q99PE8 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A spontaneous mutation gives raise to thrombocytopenia and cardiomyopathy (trac), with recessive inheritance and fully penetrant phenotype. Mice are small, infertile, and have shortened lifespan.|||ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:16352607, PubMed:16867993, PubMed:18402465). Plays an essential role in the selective transport of dietary plant sterols and cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile (PubMed:12444248, PubMed:14504269, PubMed:14657202, PubMed:19846887, PubMed:25378657). Required for normal sterol homeostasis (PubMed:12444248, PubMed:14657202). The heterodimer with ABCG8 has ATPase activity (PubMed:16352607, PubMed:16867993).|||Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.|||Cell membrane|||Cholesterol transport is inhibited by vanadate and by beryllium fluoride.|||Detected in liver and jejunum (PubMed:12444248, PubMed:15040800, PubMed:18402465, PubMed:25378657). Detected on enterocyte villi (at protein level) (PubMed:15040800). Expressed in jejunum, ileum and, at lower level, in the liver (PubMed:11138003, PubMed:11907139, PubMed:11099417, PubMed:12444248, PubMed:25378657).|||Heterodimer with ABCG8.|||Mice deficient for both Abcg5 and Abcg8 appear healthy and are fertile, but display strongly increased levels of the food-derived plant sterols sitosterol and campesterol in liver and blood plasma (PubMed:12444248, PubMed:14657202, PubMed:25378657). When mice are fed chow containing 0.02% cholesterol, cholesterol levels in blood plasma and in liver are considerably lower than in wild-type (PubMed:12444248, PubMed:14657202). In spite of the increased plasma and liver levels of plant sterols, and the decreased cholesterol levels, the total sterol levels in plasma and liver are closely similar in wild-type and mutant mice (PubMed:14657202). When mice are fed chow containing 2% cholesterol, plasma cholesterol levels remain stable in wild-type, but increase 2.4-fold in mutant mice. In the liver of mice kept on chow containing 2% cholesterol, cholesterol levels increase 3-fold for wild-type mice and 18-fold for mutant mice, resulting in much higher cholesterol levels than in wild-type livers (PubMed:12444248). Dietary cholesterol absorption appears normal in mutant mice, but the absorption of dietary cholestanol, campesterol and sitosterol is increased (PubMed:12444248). At the same time, mutant mice have very low cholesterol levels in bile, suggesting that the increased hepatic cholesterol levels are due to impaired cholesterol secretion into bile (PubMed:12444248). Likewise, the levels of the food-derived plant sterols stigmasterol, sitosterol, campesterol and brassicasterol are strongly decreased in bile from mutant mice (PubMed:14657202). In contrast, biliary phospholipid and bile acid levels appear unchanged relative to wild-type (PubMed:12444248). The blood plasma of mice with liver-specific or intestine-specific disruption of Abcg5 and Abcg8 has nearly normal levels of cholesterol, and mildly increased levels of sitosterol and campesterol (PubMed:25378657). Mice with intestine-specific disruption of Abcg5 and Abcg8 have strongly increased levels of sitosterol and campesterol in enterocytes, similar to that observed for mice with complete gene disruption (PubMed:25378657). In addition, they display strongly increased levels of sitosterol and campesterol in bile (PubMed:25378657). Mice with liver-specific disruption of Abcg5 and Abcg8 have slightly increased levels of campesterol and sitosterol in the liver, and normal, low levels of sitosterol and campesterol in bile (PubMed:25378657). Enterocytes and liver from mice with liver-specific or intestine-specific disruption of Abcg5 and Abcg8 have normal cholesterol levels (PubMed:25378657).|||N-glycosylated (PubMed:12208867, PubMed:12444248, PubMed:16867993, PubMed:15040800, PubMed:15054092, PubMed:18402465, PubMed:25378657). N-glycosylation is important for efficient export out of the endoplasmic reticulum (PubMed:15054092).|||The Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. Within this motif, the conserved Lys is essential for transport activity mediated by the heterodimer with ABCG8.|||Up-regulated in liver and small intestine by cholesterol feeding (PubMed:11099417). Up-regulated via the oxysterols receptor LXR/retinoic X receptor (LXR/RXR) pathway (PubMed:14657202). Endotoxin (LPS) significantly decreased mRNA levels in the liver but not in the small intestine (PubMed:12777468). http://togogenome.org/gene/10090:Nxph4 ^@ http://purl.uniprot.org/uniprot/G3X9N5|||http://purl.uniprot.org/uniprot/Q8BTD1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the neurexophilin family.|||May be signaling molecules that resemble neuropeptides.|||Secreted http://togogenome.org/gene/10090:Mrps9 ^@ http://purl.uniprot.org/uniprot/Q9D7N3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS9 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Atn1 ^@ http://purl.uniprot.org/uniprot/O35126 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Expressed as early as 5 days and thereafter shows little variation throughout 17 days.|||In vascular smooth muscle, induced by angiotensin II, FGF; PGF and IL1B.|||Interacts with BAIAP2, WWP1, WWP2, WWP3 and RERE. Interacts (via its N-terminus) with MTG8; the interaction enhances transcriptional repression of MTG8. Interacts with PQBP1 (By similarity). Interacts with NR2E1; the interaction represses the transcriptional activity of NR2E1. Interacts with FAT1 (via a C-terminal domain).|||Nucleus|||Phosphorylated in vitro by MAPK8/JNK1 on Ser-724.|||The mouse model of DRPLA with 129 CAG repeats (Q129) exhibited severe neurological defects similar to those of juvenile-onset DRPLA patients including age-dependent and region-specific presynaptic dysfunction in the globus pallidus and cerebellum. Progressive shrinkage of distal dendrites of Purkinje cells and decreased currents through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and gamma-aminobutyrate type A receptors in CA1 neurons was observed. There is progressive brain atrophy.|||The poly-Gln region of Atn1 is polymorphic (3 to 8 repeats).|||Transcriptional corepressor. Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of the poly-Q repeats (By similarity). Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation.|||Widely expressed. Most abundant in the brain.|||perinuclear region http://togogenome.org/gene/10090:Wdr59 ^@ http://purl.uniprot.org/uniprot/Q8C0M0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as a E3 ubiquitin-protein ligase toward GATOR1. In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex.|||Belongs to the WD repeat WDR59 family.|||Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids (By similarity). Interacts with DDB1-CUL4A/B E3 ligase complexes (PubMed:17041588).|||Lysosome membrane|||The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated. http://togogenome.org/gene/10090:Pcnx3 ^@ http://purl.uniprot.org/uniprot/Q8VI59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the pecanex family.|||Membrane http://togogenome.org/gene/10090:Sult5a1 ^@ http://purl.uniprot.org/uniprot/Q91X36 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Uty ^@ http://purl.uniprot.org/uniprot/E9PWW8|||http://purl.uniprot.org/uniprot/G3X9F2|||http://purl.uniprot.org/uniprot/Q3UQE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UTX family.|||Nucleus http://togogenome.org/gene/10090:Or52s6 ^@ http://purl.uniprot.org/uniprot/E9Q838|||http://purl.uniprot.org/uniprot/Q7TRR0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Six1 ^@ http://purl.uniprot.org/uniprot/Q3V2C3|||http://purl.uniprot.org/uniprot/Q62231|||http://purl.uniprot.org/uniprot/Q8BSP4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SIX/Sine oculis homeobox family.|||Cytoplasm|||Expressed in phalangeal tendons and in skeletal muscle and in head and body mesenchyme.|||First expressed at 8.2-8.5 dpc of embryo development in the anterior head mesoderm and developing pharyngeal pouches. Expression in the developing limb begins at 11 dpc and is more pronounced dorsally. It progresses into the developing phalanges at 13.5 dpc. In the developing inner ear detected in the otic placode and the surrounding surface ectoderm at 8.5 dpc. Expression became prominent at the invaginating otic pit and the nascent otic vesicle at 9.5 dpc. At 10.5 dpc, expression was limited to the ventral half of the otic vesicle. Subsequently, the expression became gradually restricted to the cochlear region at 11.5 dpc and 12.5 dpc. At later stages detected exclusively in the cochlea at 14.5 dpc, and the expression in the cochlear duct persisted in the neonate. In the developing kidney, is expressed in the uninduced metanephric mesenchyme at 10.5 dpc and in the induced mesenchyme around the ureteric bud at 11.5 dpc. At 17.5 dpc to P0, expression becomes restricted to a subpopulation of collecting tubule epithelial cells.|||Interacts with DACH1 (PubMed:14628042). Interacts with EYA1 (PubMed:15141091). Interacts with EYA2 (By similarity). Interacts with CDH1 (By similarity). Interacts with TBX18 (By similarity). Interacts with CEBPA (PubMed:27923061). Interacts with CEBPB (PubMed:27923061). Interacts with EBF2 (PubMed:27923061).|||Nucleus|||Perinatal lethality. Mice show failure in renal organogenesis, a severe reduction of most migratory hypaxial muscles including those of the forelimb, diaphragm and tongue, and severe rib-cage deformation. Besides, mice display craniofacial defects, including loss of inner ear structures. Pax2, Six2 and Sall1 expression is markedly reduced in the metanephric mesenchyme at 10.5 dpc during kidney development. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland.|||Phosphorylated during interphase; becomes hyperphosphorylated during mitosis. Hyperphosphorylation impairs binding to promoter elements (By similarity).|||Transcription factor that is involved in the regulation of cell proliferation, apoptosis and embryonic development (PubMed:12215533, PubMed:12668636, PubMed:12834866, PubMed:14628042, PubMed:14695375). Plays an important role in the development of several organs, including kidney, muscle and inner ear (PubMed:12668636, PubMed:12783782, PubMed:12834866, PubMed:14628042, PubMed:14695375). Depending on context, functions as transcriptional repressor or activator (PubMed:14628042). Lacks an activation domain, and requires interaction with EYA family members for transcription activation (By similarity). Mediates nuclear translocation of EYA1 and EYA2 (By similarity). Binds the 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the MYOG promoter and CIDEA enhancer (By similarity). Regulates the expression of numerous genes, including MYC, CCNA1, CCND1 and EZR (PubMed:16488997). Acts as activator of the IGFBP5 promoter, probably coactivated by EYA2 (PubMed:11978764). Repression of precursor cell proliferation in myoblasts is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex (PubMed:14628042). During myogenesis, seems to act together with EYA2 and DACH2. Regulates the expression of CCNA1 (By similarity). Promotes brown adipocyte differentiation (PubMed:27923061).|||Ubiquitinated by the anaphase promoting complex (APC), leading to its proteasomal degradation. http://togogenome.org/gene/10090:Rhox1 ^@ http://purl.uniprot.org/uniprot/B1APN4|||http://purl.uniprot.org/uniprot/Q4TU92 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Arhgef16 ^@ http://purl.uniprot.org/uniprot/Q3U5C8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Guanyl-nucleotide exchange factor of the RHOG GTPase stimulating the exchange of RHOG-associated GDP for GTP. May play a role in chemotactic cell migration by mediating the activation of RAC1 by EPHA2. May also activate CDC42 (By similarity).|||Interacts with ELMO2, EPHA2, RAC1 and RHOG; mediates activation of RAC1 by EPHA2. Interacts with TAX1BP3 (via PDZ domain) (By similarity).|||The PDZ-binding motif mediates interaction with TAX1BP3. http://togogenome.org/gene/10090:Actr5 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ89 ^@ Similarity ^@ Belongs to the actin family. http://togogenome.org/gene/10090:Nnt ^@ http://purl.uniprot.org/uniprot/Q8BGK0 ^@ Similarity ^@ In the N-terminal section; belongs to the AlaDH/PNT family. http://togogenome.org/gene/10090:Mtmr6 ^@ http://purl.uniprot.org/uniprot/Q8VE11 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by phosphatidylserine and/or phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P) (By similarity). Interaction with MTMR9 increases catalytic activity towards phosphatidylinositol 3,5-bisphosphate (By similarity).|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Homodimer (By similarity). Heterodimer (via C-terminus) with MTMR9 (via C-terminus) (PubMed:23188820, PubMed:12890864). Interacts with ALKBH4 (By similarity). Interacts with KCNN4 (By similarity). Interacts (via GRAM domain) with RAB1B (in GDP-bound form); the interaction regulates MTMR6 recruitment to the endoplasmic reticulum-Golgi intermediate compartment (PubMed:23188820).|||Isoform 1: Ubiquitously expressed including in heart, brain, spleen, lung, liver, muscle, kidney and testis (at protein level) (PubMed:23188820). Isoform 2: Expressed in testis (at protein level) (PubMed:23188820).|||Phosphatase that acts on lipids with a phosphoinositol headgroup. Dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,5-bisphosphate. Binds with high affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) but also to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), and phosphatidylinositol 5-phosphate (PtdIns(5)P), phosphatidic acid and phosphatidylserine (By similarity). Negatively regulates ER-Golgi protein transport (By similarity). Probably in association with MTMR9, plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3-phosphate in membrane ruffles (PubMed:24591580). Acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4(+) T-cells possibly by decreasing intracellular levels of phosphatidylinositol 3-phosphate. Negatively regulates proliferation of reactivated CD4(+) T-cells. In complex with MTMR9, negatively regulates DNA damage-induced apoptosis. The formation of the MTMR6-MTMR9 complex stabilizes both MTMR6 and MTMR9 protein levels (By similarity).|||The C-terminus domain (aa 502-617) mediates interaction with MTMR9.|||The GRAM domain is required for cell membrane localization.|||ruffle membrane http://togogenome.org/gene/10090:Tm9sf4 ^@ http://purl.uniprot.org/uniprot/Q8BH24 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface.|||Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.|||Early endosome|||Golgi apparatus|||Membrane http://togogenome.org/gene/10090:Fam83g ^@ http://purl.uniprot.org/uniprot/Q5SWY7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ BMP signaling induces the phosphorylation by BMPR1A at Ser-609, Ser-613 and Ser-615. Phosphorylation at Ser-609 is necessary for the activation of SMAD4-independent BMP target genes such as NEDD9 and ASNS.|||Belongs to the FAM83 family.|||Interacts with SMAD1 (via MH2 domain); in a SMAD4-independent manner.|||Nucleus|||Substrate for type I BMP receptor kinase involved in regulation of some target genes of the BMP signaling pathway. Also regulates the expression of several non-BMP target genes, suggesting a role in other signaling pathways.|||cytosol http://togogenome.org/gene/10090:Fbn2 ^@ http://purl.uniprot.org/uniprot/Q61555 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibrillin family.|||Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles (PubMed:20855508). Fibrillin-2-containing microfibrils regulate the early process of elastic fiber assembly. Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (PubMed:20855508).|||Hormone secreted by trophoblasts that promotes trophoblast invasiveness (By similarity). Has glucogenic activity: is able to increase plasma glucose levels (PubMed:32329225).|||Interacts with BMP2, BMP4, BMP7, BMP10 and GDF5. Interacts with MFAP2 and MFAP5. Interacts with ADAMTSL5. Interacts with MFAP4.|||Limb-patterning defects characterized by bilateral syndactyly due to disorganized matrix (PubMed:11470817). Digit fusion involves both soft and hard tissues and is associated with reduced apoptosis at affected sites (PubMed:11470817). Mice show a well developed and morphologically normal aortic wall (PubMed:16407178). Mice display a low bone mass phenotype that is associated with reduced bone formation (PubMed:20855508).|||N-glycosylated.|||O-glycosylated on serine residues by POGLUT2 and POGLUT3.|||Secreted|||Strongly expressed during the first week of osteoblast differentiation.|||Widely expressed.|||extracellular matrix http://togogenome.org/gene/10090:P4hb ^@ http://purl.uniprot.org/uniprot/P09103 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein disulfide isomerase family.|||Cell membrane|||Endoplasmic reticulum|||Endoplasmic reticulum lumen|||Heterodimer; heterodimerizes with the protein microsomal triglyceride transfer MTTP. Homodimer. Monomers and homotetramers may also occur. Interacts with P4HA2, forming a heterotetramer consisting of 2 alpha subunits (P4HA2) and 2 beta (P4HB), where P4HB plays the role of a structural subunit; this tetramer catalyzes the formation of 4-hydroxyproline in collagen (PubMed:7753822). Also constitutes the structural subunit of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity. Binds UBQLN1. Interacts with ERO1B (By similarity). Interacts with ILDR2 (PubMed:33863978). Interacts with ERN1/IRE1A (via N-terminus); the interaction is enhanced by phosphorylation of P4HB by FAM20C in response to endoplasmic reticulum stress and results in attenuation of ERN1 activity (By similarity).|||In the mammary gland, expressed at higher levels in lactating mice than in virgin mice.|||Melanosome|||Phosphorylation of Ser-359 by FAM20C is induced by endoplasmic reticulum stress and results in a functional switch from oxidoreductase to molecular chaperone. It also promotes interaction with ERN1.|||This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP (By similarity). Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). http://togogenome.org/gene/10090:Otud1 ^@ http://purl.uniprot.org/uniprot/Q9CUB6 ^@ Domain|||Function ^@ Deubiquitinating enzyme that specifically hydrolyzes 'Lys-63'-linked polyubiquitin to monoubiquitin. Required for the stability and translation of a subset mRNAs with a high abundance of rare codons by mediating deubiquitination of 40S ribosomal protein RPS10/eS10, thereby antagonizing ZNF598-mediated 40S ubiquitination. The abundance of rare codons in mRNAs can limit the translation rate and can lead to ribosome collisions that trigger activation of ribosome quality control (RQC) pathway by ZNF598. OTUD1-mediated deubiquitination prevents activation of the RQC and subsequent dissociation of ribosomes and stimulates formation of polysomes and translation.|||Specificity is not given by the S1' ubiquitin-binding site within the OTU domain (composed of the Cys-, His- and Variable-loops).|||The UIM repeat increases the specificity and efficiency of the enzyme toward 'Lys-63'-linked polyubiquitin. http://togogenome.org/gene/10090:Pde9a ^@ http://purl.uniprot.org/uniprot/O70628|||http://purl.uniprot.org/uniprot/Q8BSU4 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE9 subfamily.|||Binds 1 Mg(2+) ions per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Binds magnesium less tightly than zinc.|||Binds 1 Zn(2+) ion per subunit. Binds 2 divalent metal cations per subunit: site 1 preferentially binds zinc, while site 2 has a preference for magnesium. Tightly binds zinc.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Endoplasmic reticulum|||Golgi apparatus|||Highly expressed in kidney. Lower levels in liver, lung and brain (PubMed:9624145). Widely expressed in brain, with highest expression in cerebellar Purkinje cells (PubMed:14501210). Present in heart (at protein level) (PubMed:25799991).|||Homodimer.|||Inhibited by SCH 51866 and moderately, by zaprinast. Specifically inhibited by PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) (PubMed:22328573).|||Mice hearts develop less dilation and dysfunction when exposed to sustained pressure overload.|||Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes (PubMed:9624145). Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart (PubMed:25799991). Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein (Probable). In brain, involved in cognitive function, such as learning and long-term memory (PubMed:22328573, PubMed:24746365).|||perinuclear region|||ruffle membrane|||sarcolemma http://togogenome.org/gene/10090:Cyp1a1 ^@ http://purl.uniprot.org/uniprot/P00184|||http://purl.uniprot.org/uniprot/Q05A20 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15alpha and C16alpha positions. Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation. Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system. Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer. May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent).|||Belongs to the cytochrome P450 family.|||By 3-methylcholanthrene (3MC).|||Cytochromes P450 are a group of heme-thiolate monooxygenases. They oxidize a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Cytoplasm|||Endoplasmic reticulum membrane|||Interacts with cytosolic chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria. Interacts (via mitochondrial targeting signal) with TOMM40 (via N-terminus); this interaction is required for translocation across the mitochondrial outer membrane.|||Membrane|||Microsome membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Kxd1 ^@ http://purl.uniprot.org/uniprot/Q80XH1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (By similarity). May also be involved in the biogenesis of lysosome-related organelles such as melanosomes (PubMed:22554196).|||Belongs to the KXD1 family.|||Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN (By similarity). Associates with the BLOC-1 complex. Interacts with BLOC1S1. Interacts with DTNBP1/BLOC1S7 (via coiled-coil domain) (PubMed:22554196).|||Lysosome membrane|||Show defects in the lysosome-related organelles (LRO) biogenesis, mimicking mildly the human Hermansky-Pudlak syndrome (HPS).|||Widely expressed. http://togogenome.org/gene/10090:Kdm5a ^@ http://purl.uniprot.org/uniprot/Q3UXZ9 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JARID1 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4' (PubMed:17320161, PubMed:17320163). Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif. May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (By similarity). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (PubMed:21960634). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (By similarity).|||Interacts with RB1, ESR1, MYC, MYCN and LMO2 (By similarity). Interacts with SUZ12; the interaction is direct (PubMed:20064375). Interacts with BMAL1 and CLOCK (PubMed:21960634). Interacts with HDAC1; this interaction impairs histone deacetylation by HDAC1 (PubMed:21960634). Interacts (via PHD-type 1 zinc finger) with histone H3 unmodified at 'Lys-4' and (via PHD-type 3 zinc finger) with histone H3 di- and trimethylated at 'Lys-4' (By similarity).|||Mice are grossly normal, except that they exhibit behavioral abnormalities when held upside down by the tail, and slight hematological defects.|||Nucleus|||The GSGFP motif is required for the interaction with SUZ12 (PubMed:20064375). The ARID domain specifically binds to the CCGCCC motif and is required for the lysine-specific histone demethylase activity. The PHD-type 3 zinc finger is required for the interaction with histone H3 di- and trimethylated at 'Lys-4' (By similarity).|||nucleolus http://togogenome.org/gene/10090:Srpk3 ^@ http://purl.uniprot.org/uniprot/Q9Z0G2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.|||Exclusively expressed in skeletal and heart muscle.|||Expressed from embryogenesis to adulthood.|||Mice are viable to adulthood but display defects in skeletal muscle growth including reduced muscle mass, marked increase in centrally placed nuclei and disorganized intermyofibrillar network.|||Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains. Phosphorylates the SR splicing factor SRSF1 and the lamin-B receptor (LBR) in vitro. Required for normal muscle development. http://togogenome.org/gene/10090:Lims2 ^@ http://purl.uniprot.org/uniprot/Q91XD2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors.|||Cell membrane|||Detected in heart, lung, kidney, liver, urinary bladder, fat, skin, skeletal muscle, uterus, large intestine and testis.|||Interacts with integrin-linked protein kinase 1 (ILK) via the first LIM domain, and in competition with LIMS1. Part of the heterotrimeric IPP complex composed of integrin-linked kinase (ILK), LIMS1 or LIMS2, and PARVA (By similarity). Interacts with TGFB1I1.|||Not detectable during early stages of embryogenesis. Detected at low levels at 14.5 dpc and 15.5 dpc. Highly expressed at 17.5 dpc.|||focal adhesion http://togogenome.org/gene/10090:Or6k6 ^@ http://purl.uniprot.org/uniprot/E9Q0M4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fndc3c1 ^@ http://purl.uniprot.org/uniprot/Q6DFV6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FNDC3 family.|||Membrane http://togogenome.org/gene/10090:Dcaf8 ^@ http://purl.uniprot.org/uniprot/Q8N7N5 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat DCAF8 family.|||Cytoplasm|||Expressed in the brain at 8.5 dpc, 9.5 dpc and 10.5 dpc.|||Expressed in the brain.|||Interacts with DDB1, CUL4A and CUL4B. Interacts with KPNA1, KPNB1 and XPO1.|||May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.|||Nucleus|||The homozygous loop-tail (Lp) mouse has a severe neural tube closure defect, analogous to the craniorachischisis phenotype seen in humans. This gene has been mapped to The Lp critical region. http://togogenome.org/gene/10090:Or8c15 ^@ http://purl.uniprot.org/uniprot/K7N678 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm13290 ^@ http://purl.uniprot.org/uniprot/Q8CD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Ctif ^@ http://purl.uniprot.org/uniprot/Q6PEE2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CTIF family.|||Interacts with NCBP1/CBP80; the interaction is direct. Associates with the eukaryotic translation initiation factor 3 (eIF-3) complex (By similarity).|||Specifically required for the pioneer round of mRNA translation mediated by the cap-binding complex (CBC), that takes place during or right after mRNA export via the nuclear pore complex (NPC). Acts via its interaction with the NCBP1/CBP80 component of the CBC complex and recruits the 40S small subunit of the ribosome via eIF3. In contrast, it is not involved in steady state translation, that takes place when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. Also required for nonsense-mediated mRNA decay (NMD), the pioneer round of mRNA translation mediated by the cap-binding complex playing a central role in nonsense-mediated mRNA decay (NMD) (By similarity).|||Widely expressed.|||perinuclear region http://togogenome.org/gene/10090:Kcnc4 ^@ http://purl.uniprot.org/uniprot/A0A571BG98|||http://purl.uniprot.org/uniprot/Q8R1C0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.4/KCNC4 sub-subfamily.|||Homotetramer (Probable). Heterotetramer of potassium channel proteins (By similarity).|||Membrane|||Phosphorylation of serine residues in the inactivation gate inhibits rapid channel closure.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||The tail may be important in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||This protein mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient (By similarity). http://togogenome.org/gene/10090:Zfp827 ^@ http://purl.uniprot.org/uniprot/Q505G8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of a ribonucleoprotein complex composed at least of HNRNPK, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation. Could also recruit the nucleosome remodeling and histone deacetylase/NuRD complex to telomeric regions of chromosomes to regulate chromatin remodeling as part of telomere maintenance.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, HNRNPK and HNRNPL. Interacts with the nucleosome remodeling and histone deacetylase/NuRD complex. Interacts with RBBP4; the interaction is direct and recruits RBBP4, a component of the NuRD complex, to telomeres.|||telomere http://togogenome.org/gene/10090:Usp50 ^@ http://purl.uniprot.org/uniprot/Q6P8X6 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the peptidase C19 family.|||May recognize and hydrolyze the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins (By similarity).|||The human ortholog is inactive. http://togogenome.org/gene/10090:Ftsj3 ^@ http://purl.uniprot.org/uniprot/Q9DBE9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. SPB1 subfamily.|||Citrullinated by PADI4.|||Interacts with NIP7.|||RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation.|||nucleolus http://togogenome.org/gene/10090:Prc1 ^@ http://purl.uniprot.org/uniprot/G3UW86|||http://purl.uniprot.org/uniprot/G3UY19|||http://purl.uniprot.org/uniprot/Q99K43 ^@ Developmental Stage|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAP65/ASE1 family.|||Cytoplasm|||During the stages 11.5-13.5 dpc it is expressed in most embryonic tissues. Within the telencephalon, it is predominantly expressed inside the ventricular zone where expression reaches its peak at 15.5 dpc and starts to decrease by 18.5 dpc. Expression is also observed in mitotically active cells outside the telencephalon, but not in adult brain.|||Homodimer. Interacts with the C-terminal Rho-GAP domain and the basic region of RACGAP1. The interaction with RACGAP1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. Interacts (via N-terminus) with the C-terminus of CENPE (via C-terminus); the interaction occurs during late mitosis. Interacts (via N-terminus) with KIF4A (via C-terminus); the interaction is required for the progression of mitosis. Interacts (via N-terminus) with KIF23 (via C-terminus); the interaction occurs during late mitosis. Interacts with KIF14 and KIF20A. Interacts with PLK1. Interacts with KIF20B.|||Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression.|||Microtubule binding occurs via a basic patch in the central spectrin-like domain and requires also the unstructured C-terminal domain.|||Midbody|||Nucleus|||Phosphorylation by CDK1 in early mitosis holds PRC1 in an inactive monomeric state, during the metaphase to anaphase transition, PRC1 is dephosphorylated, promoting interaction with KIF4A, which then translocates PRC1 along mitotic spindles to the plus ends of antiparallel interdigitating microtubules. Dephosphorylation also promotes MT-bundling activity by allowing dimerization. Phosphorylation by CDK1 prevents PLK1-binding: upon degradation of CDK1 at anaphase and dephosphorylation, it is then phosphorylated by PLK1, leading to cytokinesis (By similarity).|||Probable intron retention.|||spindle pole http://togogenome.org/gene/10090:Sde2 ^@ http://purl.uniprot.org/uniprot/Q8K1J5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SDE2 family.|||Both SDE2-UBL and the mature SDE2 are polyubiquitinated.|||Cytoplasm|||Inhibits translesion DNA synthesis by preventing monoubiquitination of PCNA, this is necessary to counteract damage due to ultraviolet light-induced replication stress (By similarity). SDE2 is cleaved following PCNA binding, and its complete degradation is necessary to allow S-phase progression following DNA damage (By similarity).|||Interacts (via PIP-box) with PCNA; the interaction is direct and prevents ultraviolet light induced monoubiquitination of PCNA (By similarity). Interacts with FBL/fibrillarin (By similarity). Interacts with CACTIN (By similarity). Interacts with SF3B1 (By similarity). Interacts with U2AF1 (By similarity).|||Nucleus|||Plays a role in pre-mRNA splicing by facilitating excision of relatively short introns featuring weak 3'-splice sites (ss) and high GC content (By similarity). May recruit CACTIN to the spliceosome (By similarity).|||Plays a role in ribosome biogenesis by enabling SNORD3- and SNORD118-dependent cleavage of the 47S rRNA precursor (By similarity). Binds ncRNA (non-coding RNA) including the snoRNAs SNORD3 and SNORD118 (By similarity).|||The PIP-box (PCNA interacting peptide) motif mediates both the interaction with PCNA and cleavage of the SDE2 precursor by a deubiquitinating enzyme.|||The SAP domain is necessary for specific binding to DNA.|||The propeptide displays a ubiquitin-like fold.|||Upon binding to PCNA, the N-terminal UBL (ubiquitin-like) propeptide is cleaved at Gly-77 by an unidentified deubiquitinating enzyme; the resulting mature SDE2 is degraded by the DCX(DTL) complex in a cell cycle- and DNA damage dependent manner. http://togogenome.org/gene/10090:5730455P16Rik ^@ http://purl.uniprot.org/uniprot/Q9CYI0 ^@ Function|||Subunit ^@ Interacts with TBC1D23; this interaction may be indirect.|||May have a role in spermatogenesis. http://togogenome.org/gene/10090:Vmn1r246 ^@ http://purl.uniprot.org/uniprot/K9J7H2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Thrb ^@ http://purl.uniprot.org/uniprot/P37242|||http://purl.uniprot.org/uniprot/Q3UZT5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Binds DNA as a dimer; homodimer and heterodimer with RXRB. Interacts with the coactivators NCOA1/SRC1, NCOA2/GRIP1, NCOA7 and MED1/TRAP220 in a ligand-inducible manner. Interacts with the corepressor NCOR1 in absence of ligand (By similarity). Interacts with C1D. Interacts with NR2F6; the interaction impairs the binding of the THRB homodimer and THRB:RXRB heterodimer to T3 response elements. Interacts with PRMT2 and THRSP (By similarity). Interacts with TACC1; this interaction is decreased in the presence of thyroid hormone T3 (By similarity).|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.|||Nucleus http://togogenome.org/gene/10090:Npdc1 ^@ http://purl.uniprot.org/uniprot/Q64322 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NPDC1/cab-1 family.|||Expressed in the brain and nervous system. Not detected in liver, heart, skeletal muscle, spleen, pancreas, pituitary and adrenal glands. Expression increases when cultured neural cells are growth-arrested and begin to differentiate.|||Membrane|||Suppresses oncogenic transformation in neural and non-neural cells and down-regulates neural cell proliferation. Might be involved in transcriptional regulation. http://togogenome.org/gene/10090:Ngdn ^@ http://purl.uniprot.org/uniprot/Q9DB96 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAS10 family.|||Cytoplasm|||Expressed in testis, ovary, spleen, kidney, hippocampus and cerebellum (at protein level). Expressed in testis, ovary, spleen, kidney, brain.|||Interacts with CPEB1 and EIF4E.|||Nucleus|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Its dissociation from the complex determines the transition from state pre-A1 to state pre-A1* (By similarity). Inhibits mRNA translation in a cytoplasmic polyadenylation element (CPE)-dependent manner (PubMed:16705177).|||axon|||centromere|||dendrite|||filopodium|||nucleolus http://togogenome.org/gene/10090:Zfp131 ^@ http://purl.uniprot.org/uniprot/Q8K3J5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expression found as early as 8.5 dpc. High expression is found in the developing limb buds of embryos.|||May be involved in transcriptional regulation as a repressor of ESR1/ER-alpha signaling (By similarity). Plays a role during development and organogenesis as well as in the function of the adult central nervous system.|||Monosumoylated at Lys-598 by CBX4 and UHRF2. Sumoylation may potentiate ZNF131 inhibition of estrogen signaling. Sumoylation does not interfere with ubiquitination (By similarity).|||Nucleus|||Ubiquitinated.|||Ubiquitously expressed. Predominant expression is found in the developing central nervous system with strongest signals in the forebrain, midbrain, and hindbrain areas and in the neural tube. http://togogenome.org/gene/10090:Lyve1 ^@ http://purl.uniprot.org/uniprot/Q8BHC0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked. Interacts with PDGFB and IGFBP3. Forms a transient ternary complex with PDGFB and PDGFRB in TGN.|||Ligand-specific transporter trafficking between intracellular organelles (TGN) and the plasma membrane. Plays a role in autocrine regulation of cell growth mediated by growth regulators containing cell surface retention sequence binding (CRS). May act as a hyaluronan (HA) transporter, either mediating its uptake for catabolism within lymphatic endothelial cells themselves, or its transport into the lumen of afferent lymphatic vessels for subsequent re-uptake and degradation in lymph nodes (PubMed:10187853). Binds to pericelluar hyaluronan matrices deposited on the surface of leukocytes and facilitates cell adhesion and migration through lymphatic endothelium (By similarity).|||Membrane|||O-glycosylated. http://togogenome.org/gene/10090:Fbxl20 ^@ http://purl.uniprot.org/uniprot/Q9CZV8 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Altered electrophysiological synaptic activity, with increased frequency of miniature excitatory postsynaptic currents.|||Cytoplasm|||Highly expressed in brain.|||Interacts with SKP1 and CUL1.|||Intron retention.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Isoform 3 regulates neural transmission by binding and ubiquitinating RIMS1, a modulator of presynaptic plasticity. http://togogenome.org/gene/10090:Slc13a2 ^@ http://purl.uniprot.org/uniprot/Q9ES88 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.|||Deficient mice display increased urinary excretion of citrate, alpha-ketoglutarate, fumarate, and malate and a modest increase in succinate. Despite the increased excretion, there is no significant change in plasma citrate concentration. No other phenotypic change is identified in these mice. Transporter deficiency do not affect renal function under normal physiological conditions, nor to response to renal injury.|||Highly expressed in kidney and small intestine. Not detectable in brain, heart, stomach and skeletal muscle.|||Li(+) decreases succinate transport in the presence of Na(+), by competing at one of the three cation binding sites.|||Low-affinity sodium-dicarboxylate cotransporter, that mediates the entry of citric acid cycle intermediates, such as succinate, citrate, fumarate and alpha-ketoglutarate (2-oxoglutarate) into the small intestine and renal proximal tubule (PubMed:10966927) (By similarity). Can transport citrate in a Na(+)-dependent manner, recognizing the divalent form of citrate rather than the trivalent form which is normally found in blood (PubMed:10966927). Transports the dicarboxylate into the cell with a probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate, rendering the process electrogenic (By similarity). Has a critical role in renal dicarboxylate transport (PubMed:17410095). http://togogenome.org/gene/10090:Sars2 ^@ http://purl.uniprot.org/uniprot/Q9JJL8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.|||Catalyzes the attachment of serine to tRNA(Ser). Is also probably able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec).|||Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.|||Homodimer. The tRNA molecule probably binds across the dimer.|||Mitochondrion matrix|||Ubiquitous. http://togogenome.org/gene/10090:Gon4l ^@ http://purl.uniprot.org/uniprot/E9Q507|||http://purl.uniprot.org/uniprot/Q32NZ8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Myorg ^@ http://purl.uniprot.org/uniprot/Q69ZQ1 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 31 family.|||Endoplasmic reticulum membrane|||Expressed in brain, liver, spleen, skeletal muscle, heart, lung and kidney (PubMed:29910000). High expression is observed in the cerebellum, specifically in astrocytes (PubMed:29910000). Highly expressed in skeletal muscle (at protein level) (PubMed:19706595).|||Interacts with IGF2; this interaction is required for IGF2 secretion (PubMed:19706595).|||Knockout mice develop bilateral calcifications in the thalamus, due to the formation of calcium phosphate deposits.|||Nucleus membrane|||Putative glycosidase. Promotes myogenesis by activating AKT signaling through the maturation and secretion of IGF2 (PubMed:19706595).|||The requirement of the predicted catalytic residue Asp-462 to support myogenic function strongly suggests that MYORG is an enzymatically active glycosidase in vivo, even if concrete experimental proof for enzymatic activity is still missing.|||Up-regulated during C2C12 myogenic differentiation. http://togogenome.org/gene/10090:Klk1b3 ^@ http://purl.uniprot.org/uniprot/P00756 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subunit ^@ 7S NGF alpha chain stabilizes the 7S complex. The beta dimer promotes neurite growth. The gamma chain is an arginine-specific protease; it may also have plasminogen activator activity, as well as mitogenic activity for chick embryo fibroblasts.|||7S nerve growth factor is composed of two alpha chains, a beta dimer composed of identical chains, and two gamma chains.|||Belongs to the peptidase S1 family. Kallikrein subfamily.|||Binds 2 Zn(2+) ions per 7S complex. The Zn(2+) ions are bound at the alpha-gamma interfaces.|||This precursor is cleaved into segments to produce the active form of the gamma chain, which occurs naturally as combinations of either two or three segments held together by disulfide bonds: B1 and A, or B1, C and B2. http://togogenome.org/gene/10090:Prr14 ^@ http://purl.uniprot.org/uniprot/Q7TPN9 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Chimeric cDNA.|||Chromosome|||Expressed in skeletal myocytes with increasing expression during differentiation and in the gastrocnemius skeletal muscle in newborn and at higher levels in 10 days old mice (at protein level).|||Functions in tethering peripheral heterochromatin to the nuclear lamina during interphase, possibly through the interaction with heterochromatin protein CBX5/HP1 alpha (By similarity). Might play a role in reattaching heterochromatin to the nuclear lamina at mitotic exit (By similarity). Promotes myoblast differentiation during skeletal myogenesis, possibly by stimulating transcription factor MyoD activity via binding to CBX5/HP1 alpha (PubMed:25906157) (By similarity). Involved in the positive regulation of the PI3K-Akt-mTOR signaling pathway and in promoting cell proliferation, possibly via binding to GRB2 (By similarity).|||Interacts (via proline-rich region) with GRB2 (via SH3 domain 2). Interacts (via N-terminus) with CBX5.|||Nucleus|||Nucleus lamina|||nucleoplasm http://togogenome.org/gene/10090:Exosc5 ^@ http://purl.uniprot.org/uniprot/Q9CRA8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase PH family.|||Cytoplasm|||Homodimer. Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts with EXOSC1. Interacts with GTPBP1. Interacts with ZC3HAV1. Interacts with DDX17 only in the presence of ZC3HAV1 in an RNA-independent manner.|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes (By similarity). In vitro, EXOSC5 does not bind or digest single-stranded RNA and binds to double-stranded DNA without detectable DNase activity (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Isca2 ^@ http://purl.uniprot.org/uniprot/Q9DCB8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HesB/IscA family.|||Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. May be involved in the binding of an intermediate of Fe/S cluster assembly.|||Mitochondrion http://togogenome.org/gene/10090:Vmn1r129 ^@ http://purl.uniprot.org/uniprot/E9QA94 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cnn3 ^@ http://purl.uniprot.org/uniprot/Q9DAW9 ^@ Function|||Similarity ^@ Belongs to the calponin family.|||Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity (By similarity). http://togogenome.org/gene/10090:Atp13a5 ^@ http://purl.uniprot.org/uniprot/D3YU82|||http://purl.uniprot.org/uniprot/Q3TYU2 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.|||Membrane|||Specifically expressed in brain and stomach. http://togogenome.org/gene/10090:Dennd5b ^@ http://purl.uniprot.org/uniprot/A2RSQ0 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RAB6IP1 family.|||Guanine nucleotide exchange factor (GEF) which may activate RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity).|||Membrane|||Probable cloning artifact. http://togogenome.org/gene/10090:Ntn1 ^@ http://purl.uniprot.org/uniprot/O09118 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to its receptors; DCC, UNC5A, UNC5B, UNC5C and probably UNC5D (By similarity). Binds to its receptor; DSCAM (PubMed:18585357). Interacts with APP (PubMed:27068745).|||Cytoplasm|||In the embryo, widely expressed in the developing nervous system and in mesodermal tissues.|||Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. Binding to UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Involved in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977). It also serves as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in colorectal tumorigenesis by regulating apoptosis (By similarity).|||Secreted http://togogenome.org/gene/10090:Ccnb1ip1 ^@ http://purl.uniprot.org/uniprot/D3Z3K2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both male and female mice are sterile. Males do not make sperm and have much smaller testes, a characteristic of mutants with meiotic defects. Early stages of meiosis occur normally and full synapsis of homologous chromosomes (homologs) is achieved. However, crossover-specific recombination complexes do not assemble and crossing-overs fail. In spermatocytes, chromosomes fail to congress properly at the metaphase plate, leading to arrest and apoptosis before the first meiotic division. Mutant oocytes have a similar chromosomal phenotype but can undergo meiotic divisions and fertilization before arresting. During late meiotic prophase males, absence of Cdk2 and mismatch repair protein association from chromosome cores is correlated with the premature separation of bivalents at diplonema owing to lack of chiasmata.|||Chromosome|||Expressed predominantly in the testes and 17 day embryos (corresponding to prophase I in females). Weakly or not expressed in other tissues.|||In spermatocytes, synaptonemal complex-associated Ccnb1ip1 foci are detected by early pachynema and their number peaks during midpachynema. In late-pachytene nuclei, Ccnb1ip1 foci number descrease. At the onset of diplonema, foci are no longer detected (at protein level).|||Interacts with CCNB1, UBE2L3 and NF2.|||Nucleus|||Phosphorylated by CDK1 on serine or threonine residues (in vitro).|||Ubiquitin E3 ligase that acts as a limiting factor for crossing-over during meiosis: required during zygonema to limit the colocalization of RNF212 with MutS-gamma-associated recombination sites and thereby establish early differentiation of crossover and non-crossover sites. Later, it is directed by MutL-gamma to stably accumulate at designated crossover sites. Probably promotes the dissociation of RNF212 and MutS-gamma to allow the progression of recombination and the implementation of the final steps of crossing over. Modulates cyclin-B levels and participates in the regulation of cell cycle progression through the G2 phase. Overexpression causes delayed entry into mitosis.|||Ubiquitinated; autoubiquitinated. http://togogenome.org/gene/10090:Enox2 ^@ http://purl.uniprot.org/uniprot/Q8R0Z2 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ENOX family.|||Cell membrane|||Glycosylated.|||Inhibited by the antitumor sulfonylurea LY181984, the vabilloid capsaicin, and retinoids.|||May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock (By similarity).|||extracellular space http://togogenome.org/gene/10090:Or52b2 ^@ http://purl.uniprot.org/uniprot/Q8VGW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cpsf4l ^@ http://purl.uniprot.org/uniprot/E9Q2N0|||http://purl.uniprot.org/uniprot/G3UWW6|||http://purl.uniprot.org/uniprot/Q3TTY7|||http://purl.uniprot.org/uniprot/Q9DBA5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CPSF4/YTH1 family.|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex.|||Nucleus http://togogenome.org/gene/10090:Urgcp ^@ http://purl.uniprot.org/uniprot/Q5NCI0 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||May be involved in cell cycle progression through the regulation of cyclin D1 expression.|||Nucleus http://togogenome.org/gene/10090:Chrna4 ^@ http://purl.uniprot.org/uniprot/O70174|||http://purl.uniprot.org/uniprot/Q53YK0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-4/CHRNA4 sub-subfamily.|||Cell membrane|||Membrane|||Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-4 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors, complexes with beta-2 may be heteropentamers. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6. The heteropentamer alpha-4-beta-2 interacts with alpha-conotoxins PnIA, GID and MII (By similarity).|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Snx9 ^@ http://purl.uniprot.org/uniprot/Q3U1P2|||http://purl.uniprot.org/uniprot/Q91VH2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sorting nexin family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle membrane|||Detected in inner ear vestibula and in the cuticular plate of cochlear hair cells (at protein level).|||Homodimer, and homooligomer. Heterodimer with SNX18. Interacts with ITCH. Interacts (via SH3 domain) with TNK2, WASL and ACTR3. Identified in a complex with TNK2 and clathrin heavy chains. Identified in a complex with the AP-2 complex, clathrin and DNM2. Interacts (via SH3 domain) with DNM1 and DNM2. Identified in an oligomeric complex containing DNM1 and SNX9 (By similarity). Interacts with FCHSD1 (PubMed:23437151). Interacts with ADAM9 and ADAM15 cytoplasmic tails (PubMed:10531379).|||Involved in endocytosis and intracellular vesicle trafficking, both during interphase and at the end of mitosis. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Plays a role in endocytosis via clathrin-coated pits, but also clathrin-independent, actin-dependent fluid-phase endocytosis. Plays a role in macropinocytosis. Promotes internalization of TNFR. Promotes degradation of EGFR after EGF signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1 oligomerization. Promotes activation of the Arp2/3 complex by WASL, and thereby plays a role in the reorganization of the F-actin cytoskeleton (PubMed:23437151). Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane tubulation. Has lower affinity for membranes enriched in phosphatidylinositol 3-phosphate (By similarity).|||Phosphorylated on tyrosine residues by TNK2. Phosphorylation promotes its activity in the degradation of EGFR (By similarity).|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol phosphate. Has high affinity for phosphatidylinositol 4,5-bisphosphate, but can also bind to membranes enriched in other phosphatidylinositol phosphates.|||Ubiquitinated by ITCH.|||clathrin-coated vesicle|||ruffle|||trans-Golgi network http://togogenome.org/gene/10090:Fkbp9 ^@ http://purl.uniprot.org/uniprot/Q9Z247 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Endoplasmic reticulum lumen|||Expressed in all developmental stages.|||Inhibited by FK506.|||PPIases accelerate the folding of proteins during protein synthesis.|||Phosphorylated.|||Predominantly expressed in heart, skeletal muscle, lung, liver and kidney. Lower levels found in brain, spleen and testis. http://togogenome.org/gene/10090:Slc45a2 ^@ http://purl.uniprot.org/uniprot/P58355|||http://purl.uniprot.org/uniprot/Q541S3 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycoside-pentoside-hexuronide (GPH) cation symporter transporter (TC 2.A.2) family.|||Defects in Slc45a2 are the cause of the UW-dbr phenotype that results in loss of nearly all pigmentation in the homozygous state.|||Interacts with TYRP1.|||Mainly expressed in eyeballs and skin melanocytes (PubMed:25164149, PubMed:35469906). Also detected in kidney, colon, gall bladder and pancreas (PubMed:25164149).|||Melanosome membrane|||Membrane|||Mutant mice have clear white fur with red and transparent eyes without melanin in the retinal pigment epithelium chorioid.|||Proton-associated glucose and sucrose transporter (PubMed:25164149, PubMed:35469906). May be able to transport also fructose (PubMed:25164149). Expressed at a late melanosome maturation stage where functions as proton/glucose exporter which increase lumenal pH by decreasing glycolysis (PubMed:32966160, PubMed:35469906). Regulates melanogenesis by maintaining melanosome neutralization that is initially initiated by transient OCA2 and required for a proper function of the tyrosinase TYR (PubMed:32966160, PubMed:35469906). http://togogenome.org/gene/10090:Mrps30 ^@ http://purl.uniprot.org/uniprot/Q9D0G0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL65 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Parn ^@ http://purl.uniprot.org/uniprot/A0A0R4J0P6|||http://purl.uniprot.org/uniprot/Q8VDG3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development. Interacts with both the 3'-end poly(A) tail and the 5'-end cap structure during degradation, the interaction with the cap structure being required for an efficient degradation of poly(A) tails. Involved in nonsense-mediated mRNA decay, a critical process of selective degradation of mRNAs that contain premature stop codons. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly via its interaction with KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs, which constitutes the first step of destabilization (By similarity). Also able to recognize poly(A) tails of microRNAs such as MIR21 and H/ACA box snoRNAs (small nucleolar RNAs) leading to leading to microRNAs degradation or snoRNA increased stability (By similarity).|||Belongs to the CAF1 family.|||Cytoplasm|||Divalent metal cations. Mg(2+) is the most probable.|||Homodimer. Found in a mRNA decay complex with RENT1, RENT2 and RENT3B. Interacts with KHSRP. Interacts with CELF1/CUGBP1. Interacts with ZC3HAV1 in an RNA-independent manner. Interacts with DHX36.|||Nucleus|||Phosphorylation by MAPKAPK2, preventing GADD45A mRNA degradation after genotoxic stress.|||nucleolus http://togogenome.org/gene/10090:Trmt44 ^@ http://purl.uniprot.org/uniprot/Q9D2Q2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRM44 family.|||Cytoplasm|||Probable adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase. http://togogenome.org/gene/10090:Vegfb ^@ http://purl.uniprot.org/uniprot/P49766 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in heart, brain, kidney and skeletal muscle.|||Belongs to the PDGF/VEGF growth factor family.|||Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis. VEGF-B seems to be required for normal heart function in adult but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.|||Homodimer; disulfide-linked. Can also form heterodimer with VEGF.|||Secreted|||VEGF-B186 is O-glycosylated. http://togogenome.org/gene/10090:Ythdc1 ^@ http://purl.uniprot.org/uniprot/E9Q5K9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Embryonic lethality (PubMed:29799838). Conditional deletion in germ cells leads to infertility in both males and females: mice are viable and grossly normal but male mice lack any germ cells including mitotic spermatogonia, while female oocyte maturation is arrested at the primary follicle stage (PubMed:29799838). Ythdc1-deficient oocytes contain large cytoplasmic RNA granules, show extensive alternative polyadenylation, thereby altering 3'-UTR length, and massive alternative splicing defects (PubMed:29799838).|||Interacts with SRSF1. Interacts with SRSF2 (By similarity). Interacts with SRSF3 (PubMed:29799838). Interacts with SRSF7 (PubMed:29799838). Interacts with SRSF10 (By similarity). Interacts with CPSF6 (PubMed:29799838). Interacts with KHDRBS1/SAM68.: Interacts with TRA2B. Interacts with KHDRBS3 (By similarity). Interacts with EMD (By similarity). Interacts with RBMX (By similarity). Interacts with ZCCHC8 (By similarity).|||Nucleus|||Nucleus speckle|||Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:29262316, PubMed:29799838). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:29799838). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (By similarity). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (By similarity). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (By similarity). May also regulate alternative splice site selection (By similarity). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (By similarity). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (PubMed:29262316). Also recognizes and binds m6A on other RNA molecules (By similarity). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (By similarity). Also recognizes and binds m6A-containing single-stranded DNA (By similarity). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (PubMed:29799838).|||The YTH domain mediates RNA-binding.|||Tyrosine phosphorylated. http://togogenome.org/gene/10090:Pudp ^@ http://purl.uniprot.org/uniprot/Q9D5U5 ^@ Function|||Similarity ^@ Belongs to the HAD-like hydrolase superfamily. CbbY/CbbZ/Gph/YieH family.|||Dephosphorylates pseudouridine 5'-phosphate, a potential intermediate in rRNA degradation. Pseudouridine is then excreted intact in urine. http://togogenome.org/gene/10090:Kin ^@ http://purl.uniprot.org/uniprot/Q8K339 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated with DNA polymerase alpha, RFC1 and cyclin A, in multiprotein DNA replication complexes. Also associates with replication origins at the G1/S phase boundary and throughout the S phase in vivo (By similarity).|||Belongs to the KIN17 family.|||Cytoplasm|||Highly expressed in transformed mouse AtT20 neuroendocrine cells. Expressed at a lower level in testis, kidney, skeletal muscle, liver, lung, spleen, brain and heart and kidney. In testis, expressed at much higher levels in proliferating cells than in differentiating cells. Not detected in embryo.|||In testis, expression almost doubled from day 5 to days 17-22 postpartum (dpp) and then decreased by 28 dpp to reach a stable level in adult testis.|||Involved in DNA replication and the cellular response to DNA damage. May participate in DNA replication factories and create a bridge between DNA replication and repair mediated by high molecular weight complexes. May play a role in illegitimate recombination and regulation of gene expression. May participate in mRNA processing. Binds, in vitro, to double-stranded DNA. Also shown to bind preferentially to curved DNA in vitro and in vivo. Binds via its C-terminal domain to RNA in vitro.|||Nucleus|||Recognized by antibodies directed against the RecA protein.|||The C-terminal domain (268-393) is organized into 2 subdomains that bear structural similarities to SH3-like domains. Both subdomains adopt a similar 5-stranded beta-barrel-like fold and are connected to each other by a short linker of 5 residues. The 5 beta-sheets are packed at approximately right angles against each other. A highly conserved groove formed at the interface between the 2 subdomains, comprised of Lys residues 302 and 391 and other positively charged residues, may possibly be the site of RNA-binding (By similarity). http://togogenome.org/gene/10090:Fam163a ^@ http://purl.uniprot.org/uniprot/A9ZNB6|||http://purl.uniprot.org/uniprot/Q8CAA5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM163 family.|||Membrane http://togogenome.org/gene/10090:Kcnip2 ^@ http://purl.uniprot.org/uniprot/Q9JJ69 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the recoverin family.|||Cell membrane|||Component of heteromultimeric potassium channels (PubMed:19713751, PubMed:20943905). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). The KCND2-KCNIP2 channel complex contains four KCND2 and four KCNIP2 subunits. Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2. At least isoform 2 and isoform 3 can self-associate to form homodimers and homotetramers. Isoform 3 interacts with KCNIP1 in a calcium-dependent manner (By similarity). Interacts with KCND2 (PubMed:20943905). Isoform 1 and isoform 3 interact with KCND3 isoform 1.|||Detected in brain (at protein level) (PubMed:23713033). Expressed in brain. Highly expressed in layer IV of the cerebral cortex and in striatum and hippocampus, but expressed at low levels in cerebellum. Also expressed in heart. According to PubMed:11747815 expressed in heart at much higher levels than in brain with a preferential expression in the myocardium.|||Mice appear healthy and show no signs of cardiac dysmorphogenesis, contractile dysfunction, hypertrophy, or heart failure but are highly susceptible to the induction of polymorphic ventricular tachycardia, including arrhythmia (PubMed:11747815, PubMed:23713033). Myocytes show a complete and selective loss of I(To) current in the heart (PubMed:11747815, PubMed:23713033). This is due to the loss of KCND2 protein in the heart ventricles (PubMed:23713033).|||Palmitoylated. Palmitoylation enhances association with the plasma membrane.|||Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner (PubMed:20943905, PubMed:23713033). In vitro, modulates KCND2/Kv4.2 and KCND3/Kv4.3 currents. Involved in KCND2 and KCND3 trafficking to the cell surface. Essential for the expression of I(To) currents in the heart (PubMed:11747815, PubMed:23713033). Required for normal protein levels of KCND2 in the heart ventricle (PubMed:23713033). http://togogenome.org/gene/10090:Usp17lb ^@ http://purl.uniprot.org/uniprot/E9Q9U0 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase C19 family. USP17 subfamily.|||Detected in brain, heart, liver, lung, kidney, ovary and spleen.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Inhibited by ubiquitin aldehyde.|||May be due to competing acceptor splice site.|||Ubiquitinated.|||Up-regulated by interleukin-3 (IL-3) in the B-lymphocyte cell line Ba/F3. May also be up-regulated in response to JAK2. http://togogenome.org/gene/10090:Fpr2 ^@ http://purl.uniprot.org/uniprot/O88536 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Blocks Fam19a5-stimulated macrophage chemotaxis and phosphorylation of Erk1 and Akt1 (PubMed:29138422). Suppression of Fam19a5-mediated inhibition of Rankl-induced osteoclast differentiation (PubMed:29138422).|||Cell membrane|||High affinity receptor for N-formyl-methionyl peptides (FMLP), which are powerful neutrophil chemotactic factors (PubMed:12218158, PubMed:10477558, PubMed:19387439). Stimulates chemotaxis in immune cells to site of infection or tissue damage upon recognition of several ligands, such as FMLP, or ligand involved in cell damage, disease or inflammation (PubMed:10477558, PubMed:19497865). Receptor for the chemokine-like protein FAM19A5, mediating FAM19A5-stimulated macrophage chemotaxis and the inhibitory effect on TNFSF11/RANKL-induced osteoclast differentiation (PubMed:29138422).|||Interacts with Amyloid-beta protein 42, product of APP; the interaction takes place at the cell surface and the complex is then rapidly internalized.|||Primarily expressed in neutrophils. Not detected in vomeronasal neurons. http://togogenome.org/gene/10090:Rsph9 ^@ http://purl.uniprot.org/uniprot/Q9D9V4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flagellar radial spoke RSP9 family.|||Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB (PubMed:36417862, PubMed:34871179). Interacts with IQUB (PubMed:36417862). Interacts with RSPH3B (PubMed:34871179). Interacts with RSPH4A (PubMed:34871179). Interacts with RSPH6A (PubMed:30185526, PubMed:34871179).|||Expressed in the embryonic node at 7.5 dpc and in the nasal, lung, tracheal and brain ventricle epithelium at 18.5-19.5 dpc.|||Expressed in the testis, trachea, lung, oviduct and ependymal cells (at protein level).|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:30383886, PubMed:36417862, PubMed:34871179). Essential for both the radial spoke head assembly and the central pair microtubule stability in ependymal motile cilia (PubMed:30383886). Required for motility of olfactory and neural cilia and for the structural integrity of ciliary axonemes in both 9+0 and 9+2 motile cilia (By similarity).|||RNAi-mediated depletion in the ependymal cilia results in a near complete central pair apparatus loss and alters the ciliary beat pattern from planar to rotational (PubMed:30383886). Multiple radial spokes proteins, including those in the head, are markedly down-regulated in the cilia (PubMed:30383886).|||cilium axoneme|||flagellum axoneme|||kinocilium http://togogenome.org/gene/10090:Fbxl2 ^@ http://purl.uniprot.org/uniprot/Q8BH16 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:21343341, PubMed:23542741). Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin (By similarity). This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin (By similarity). Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (By similarity). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (By similarity). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (PubMed:21343341). The SCF(FBXL2) complex acts as a regulator of inflammation by mediating ubiquitination and degradation of TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6) (PubMed:23542741). The SCF(FBXL2) complex acts as a negative regulator of the NLRP3 inflammasome by mediating ubiquitination and degradation of NLRP3 (By similarity).|||May play a role in P. Aeruginosa-induced surfactant deficiency by inhibiting PCYT1A in a calcium-dependent manner.|||Membrane|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2. Interacts with calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2). May interact with PIK3R1. Interacts with PTPN13.|||Phosphorylated by GSK-beta (GSK3B), promoting recognition by FBXO3, leading to its ubiquitination by the SCF(FBXO3) complex.|||The CAAX motif is a signal for the geranylgeranylation of FBXL2 and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex.|||Ubiquitinated at Lys-201 by the SCF(FBXO3) complex in response to lipopolysaccharide (LPS), leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Gls ^@ http://purl.uniprot.org/uniprot/D3Z7P3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A highly mobile activation loop at the dimer-dimer interface is important for enzyme activity.|||Belongs to the glutaminase family.|||Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, the main excitatory neurotransmitter in the brain.|||Death during the first days after birth. Pups appear normal and display normal levels of activity, but their activity is disorganized. Pups do not orient to the dam, do not succeed in grasping a nipple and do not feed properly. In addition, they display altered respiration.|||Homotetramer, dimer of dimers (PubMed:22228304, PubMed:27542409). The tetramers can assemble into rod-like oligomers (in vitro), but the physiological significance of this is not clear (PubMed:23935106). Interacts with RAF1 and MAP2K2 (By similarity). Interacts with ATCAY; the interaction is direct and may control GLS localization, negatively regulating its activity (PubMed:16899818).|||Isoform 1 and isoform 2 are activated by phosphate, due to increased affinity for glutamine (PubMed:22228304, PubMed:23935106, PubMed:27542409). At phosphate concentrations above 10 mM, isoform 2 is more efficient than isoform 1.|||Mitochondrion|||Mitochondrion matrix|||Synthesized as a 74-kDa cytosolic precursor which is proteolytically processed by the mitochondrial-processing peptidase (MPP) via a 72-kDa intermediate to yield the mature mitochondrial 68- and 65-kDa subunits.|||The C-terminal ANK repeats prevent the assembly of the supra-tetrameric filaments.|||cytosol http://togogenome.org/gene/10090:Bdh1 ^@ http://purl.uniprot.org/uniprot/Q80XN0 ^@ Activity Regulation|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-132 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Homotetramer.|||Mitochondrion inner membrane|||Mitochondrion matrix|||Requires phosphatidylcholine as an allosteric activator for enzymatic activity. http://togogenome.org/gene/10090:Rab3b ^@ http://purl.uniprot.org/uniprot/Q0PD62|||http://purl.uniprot.org/uniprot/Q9CZT8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in testis, lung and brain.|||Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Golgi apparatus|||Interacts with RIMS1, RIMS2, RPH3A and RPH3AL (PubMed:12578829). The GTP-bound form interacts with GAS8/DRC4 (via coiled-coil domains) (PubMed:18396146). Interacts with GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (By similarity). Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (PubMed:18849981).|||Phosphorylation of Thr-86 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitor GDI2.|||Protein transport. Probably involved in vesicular traffic (By similarity).|||Protein transport. Probably involved in vesicular traffic. http://togogenome.org/gene/10090:Defb38 ^@ http://purl.uniprot.org/uniprot/Q7TNV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Only expressed in epididymis (caput, corpus and cauda).|||Secreted|||Synthetic Defb38 kills both Gram-negative (E.coli and P.aeruginosa) and Gram-positive (E.faecium) bacteria. http://togogenome.org/gene/10090:Eif3c ^@ http://purl.uniprot.org/uniprot/Q8R1B4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit C family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with ALKBH4, IFIT1 and IFIT2 (By similarity). Interacts with BZW2/5MP1 (By similarity).|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation. http://togogenome.org/gene/10090:Aspg ^@ http://purl.uniprot.org/uniprot/A0JNU3 ^@ Function|||Similarity|||Subunit ^@ Exhibits lysophospholipase, transacylase, PAF acetylhydrolase and asparaginase activities (By similarity). Can catalyze three types of transacylation reactions: (1) acyl transfer from 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) to the sn-1(3) positions of glycerol and 2-acylglycerol (sn-1 to -1(3) transfer), (2) acyl transfer from 1-acyl-GPC to the sn-2 positions of 1-acyl-GPC, 1-acyl-sn-glycero-3-phosphoethanolamine (1-acyl-GPE), and other lysophospholipids (sn-1 to -2 transfer) and (3) acyl transfer from 2-acyl-GPC to the sn-1 position of 2-acyl-GPC and 2-acyl-GPE (sn-2 to -1 transfer) (By similarity). Mediates the synthesis of 1-arachidonoyl species of phospholipids by transferring the arachidonoyl residue from 2-arachidonoyl lysophospholipid to the sn-1 position of 2-acyl lysophospholipid (By similarity).|||In the N-terminal section; belongs to the asparaginase 1 family.|||Monomer. http://togogenome.org/gene/10090:Elf4 ^@ http://purl.uniprot.org/uniprot/Q9Z2U4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ETS family.|||Interacts with RUNX1 (via the Runt domain); the interaction transactivates the IL3 promoter. Interacts (via its C-terminus) with PML; the interaction translocates ELF4 to PML nuclear bodies and enhances transactivation of LYZ (By similarity).|||PML body|||Transcriptional activator that binds to DNA sequences containing the consensus 5'-WGGA-3'. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of LYZ. Acts synergistically with RUNX1 to transactivate the IL3 promoter (By similarity). Transactivates the PRF1 promoter in natural killer (NK) cells and in CD8+ T cells (PubMed:34326534). Plays a role in the development and function of NK and NK T-cells and in innate immunity. Controls the proliferation and homing of CD8+ T-cells via the Kruppel-like factors KLF4 and KLF2. Controls cell senescence in a p53-dependent manner. Can also promote cellular transformation through inhibition of the p16 pathway. Is a transcriptional regulator of inflammation, controlling T-helper 17 (Th17) cells and macrophage inflammatory responses. Required for sustained transcription of anti-inflammatory genes, including IL1RN (PubMed:34326534, PubMed:35266071). Is a negative regulator of pro-inflammatory cytokines expression, including IL17A, IL1B, IL6, TNFA and CXCL1 (PubMed:34326534, PubMed:35266071). Down-regulates expression of TREM1, a cell surface receptor involved in the amplification of inflammatory responses (PubMed:34326534, PubMed:35266071). http://togogenome.org/gene/10090:Nxt2 ^@ http://purl.uniprot.org/uniprot/Q3UNA4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with NXF1, NXF2, NXF3 and NXF5.|||Cytoplasm|||Nucleus|||Regulator of protein export for NES-containing proteins. Also plays a role in mRNA nuclear export (By similarity). http://togogenome.org/gene/10090:Ncs1 ^@ http://purl.uniprot.org/uniprot/Q8BNY6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the recoverin family.|||Binds 3 calcium ions via the second, third and fourth EF-hand.|||Cell membrane|||Cytoplasm|||Golgi apparatus|||Membrane|||Monomer (By similarity). Interacts with KCND2 (By similarity). Interacts in a calcium-independent manner with PI4KB (By similarity). This binding competes with CALN2/CABP7 binding to PI4KB (By similarity). Interacts in a calcium-dependent manner with PICK1 (via AH domain) (By similarity). Interacts with ARF1, ARF3, ARF5 and ARF6 (By similarity). Interacts with IL1RAPL1 (By similarity). Interacts with RIC8A; interaction is favored in the absence of Ca(2+) and myristoylation of NCS1 is not required (By similarity).|||Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin (By similarity). Stimulates PI4KB kinase activity (By similarity). Involved in long-term synaptic plasticity through its interaction with PICK1 (By similarity). May also play a role in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel (By similarity).|||Postsynaptic density|||perinuclear region http://togogenome.org/gene/10090:Cxcr4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0N8|||http://purl.uniprot.org/uniprot/P70658 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell junction|||Cell membrane|||Early endosome|||Endosome|||Half of the embryos die by 17.5 dpc-18.5 dpc and neonates die within a few hours. Mutants display defective vascular development, cerebellar development, B-lymphopoiesis, myelopoiesis, and cardiogenesis with defective formation of the large vessels supplying the gastrointestinal tract.|||High expression during embryonic development does not seem to be associated with the differentiation of any particular cell type, but is widely utilized when there is a requirement for cell movement. Frequently associated with less differentiated cell types and down-regulated with subsequent differentiation. Detected in sites with hemopoietic potential: the yolk sac (7.5, 8.5 and 12.5 dpc) and fetal liver (12.5 dpc). During gastrulation, at 7.2 to 7.8 dpc, expressed in the mesoderm and the definitive endoderm. As gastrulation pattern fades (8.5 dpc), expression in the mesoderm is down-regulated, while it becomes predominant in neural ectoderm. Endodermal expression is retained in the foregut and later in a subset of foregut derivatives, including the stomach (10.5 dpc), the cystic ducts of the gall bladder and the lung epithelium (12.5 dpc). In neuronal tissue: at 10.5 and 12.5 dpc, expressed in the dorsal root ganglia, in the ventral mantle layer of the spinal cord (or basal plates), in the hindbrain. At 14.5 dpc, expression more tightly confined to the neural epithelium lining the ventricular space and to the external granular layer of the ventral rhombic lip (the developing cerebellum). Expressed in the outpocketing of the diencephalic floor at 10.5 dpc and in the developing thalamus and, to a lesser extent, the developing hypothalamus. At 14.5 dpc, restricted to the region where thalamus and hypothalamus meet. Detected in a discrete band of cells at the edge of the olfactory bulb. In the vascular system: expressed in the endothelium of numerous blood vessels, but not all, at 10.5, 11.5 and 12.5 dpc, such as vitelline/umbilical vessels, cardiac ventricular wall capillaries, facial vessels and, at 14.5 dpc, in the vasculature of the herniated gut. Expression seems to be associated with expanding vascular networks. In the heart development, expressed at 10.5 dpc in the precursor to the aortopulmonary (AP) septum. At 12.5 dpc, detected in the AP septum at the base of the outflow tract and in the atrioventricular valves. Detected in cranofacial ectoderm from 10.5 to 14.5 dpc. At 10.5 and 11.5 dpc, expressed in the Rathke pouch.|||Late endosome|||Lymphocytes, macrophages, neutrophils, microglial cells and astrocytes. Found in spleen, thymus, bone marrow, lymph nodes and, at lower levels in brain, small intestine, stomach and kidney. CXCR4-A is predominant in all tissues tested. During embryonic development, high levels are detected in the endothelium of developing blood vessels and in many regions of the developing brain including the olfactory epithelium, olfactory bulb, hippocampus, cerebellum and spinal cord.|||Lysosome|||Membrane|||Monomer. Can form homodimers. Interacts with CD164. Interacts with ARRB2; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with ARR3; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and modulates calcium mobilization. Interacts with RNF113A; the interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and subsequent degradation. Interacts (via the cytoplasmic C-terminal) with ITCH (via the WW domains I and II); the interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and leads to its degradation. Interacts with extracellular ubiquitin. Interacts with DBN1; this interaction is enhanced by antigenic stimulation. Following LPS binding, may form a complex with GDF5, HSP90AA1 and HSPA8.|||O- and N-glycosylated. N-glycosylation can mask coreceptor function. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity.|||Phosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal. Phosphorylation at Ser-331 and Ser-332 leads to recruitment of ITCH, ubiquitination and protein degradation.|||Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation (PubMed:8962122, PubMed:9295051, PubMed:9103415). Involved in the AKT signaling cascade (By similarity). Plays a role in regulation of cell migration, e.g. during wound healing. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (By similarity). Involved in hematopoiesis and in cardiac ventricular septum formation (PubMed:9634237, PubMed:9634238, PubMed:9689100). Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells (PubMed:9634237). Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival (PubMed:9634238, PubMed:9689100).|||Sulfation is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization.|||Ubiquitinated after ligand binding, leading to its degradation. Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The ubiquitin-dependent mechanism, endosomal sorting complex required for transport (ESCRT), then targets CXCR4 for lysosomal degradation. This process is dependent also on prior Ser-/Thr-phosphorylation in the C-terminal of CXCR4. Also binding of ARRB1 to STAM negatively regulates CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S. http://togogenome.org/gene/10090:Or13a19 ^@ http://purl.uniprot.org/uniprot/Q8VGL5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ropn1l ^@ http://purl.uniprot.org/uniprot/Q9EQ00 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ropporin family.|||Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB (PubMed:36417862). May interact with AKAP3 (By similarity). Interacts with FSCB; the interaction increases upon spermatozoa capacitation conditions (PubMed:27398160).|||Expressed in testis at least from P5 to P40. Expression increases with sample age. Detected in the flagella of elongated spermatids, but the expression levels reduce as the sperm matures (heads move towards the center lumen) (PubMed:23303679).|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:36417862). Important for male fertility. With ROPN1, involved in fibrous sheath integrity and sperm motility, plays a role in PKA-dependent signaling processes required for spermatozoa capacitation.|||Mutant mice have normal testicular morphology and spermatogenesis but have moderately impaired motility and increased levels of ROPN1 (PubMed:23303679). Double knockout animals for ROPN1 and ROPN1L are infertile with normal testicular morphology and spermatogenesis but defects in sperm morphology, thinning and shredding of the principal piece. Sperm is immotile (PubMed:23303679).|||Sumoylated, sumoylation decreases upon spermatozoa capacitation conditions.|||Testis-specific. Expression is restricted to germ cells.|||cilium|||flagellum http://togogenome.org/gene/10090:Zbtb6 ^@ http://purl.uniprot.org/uniprot/Q8K088 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Tenm2 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ92|||http://purl.uniprot.org/uniprot/A0A0A0MQB7|||http://purl.uniprot.org/uniprot/B9EJ72 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tenascin family. Teneurin subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Umodl1 ^@ http://purl.uniprot.org/uniprot/Q5DID3 ^@ Developmental Stage|||Subcellular Location Annotation ^@ Cell membrane|||First detected at 16.5 dpc only in olfactory epithelium (OE) and the epithelium of the vomeronasal organ (VNO). At this stage, expression in OE is punctate and is restricted to only some of the sensory neurons. At birth and postnatally, expression in these organs extends to more neurons. At 3 weeks, expression shows a smooth gradation from high apical to low basal within the layer of mature olfactory sensory neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Glp2r ^@ http://purl.uniprot.org/uniprot/A0A158RFU9|||http://purl.uniprot.org/uniprot/Q5IXF8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Membrane|||This is a receptor for glucagon-like peptide 2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity). http://togogenome.org/gene/10090:Cfap65 ^@ http://purl.uniprot.org/uniprot/Q3V0B4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Begins to be significantly expressed at postnatal day 15, reachs a peak at postnatal day 22 and then maintains stable expression level.|||Belongs to the CFAP65 family.|||Cytoplasm|||Deficient male are infertile whereas female mutants could give birth. Deficient male show severe morphological abnormalities of the sperm flagella. The majority of spermatozoa display absent or short flagella and the flagellar axoneme is completely disorganised.|||Interacts with CFAP47.|||Plays a role in flagellar formation and sperm motility.|||Predominantly expressed in testis (PubMed:31571197). Highly expressed in round and elongating spermatids (PubMed:31571197, PubMed:31413122). Expressed also in certain ciliated organs, such as the brain, lung and kidney (PubMed:31413122).|||acrosome membrane|||flagellum membrane http://togogenome.org/gene/10090:Naa30 ^@ http://purl.uniprot.org/uniprot/Q8CES0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family. MAK3 subfamily.|||Catalytic subunit of the N-terminal acetyltransferase C (NatC) complex. Catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Leu-Ala and Met-Leu-Gly. Necessary for the lysosomal localization and function of ARL8B sugeesting that ARL8B is a NatC substrate.|||Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Prss44 ^@ http://purl.uniprot.org/uniprot/Q402U7 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cytoplasm|||In testis, expressed at all stages from the late pachytene primary spermatocyte to the secondary spermatocyte. Not detected at day 7 after birth. Expression is detected at day 14 and increases dramatically at day 21 and reach a peak at day 28 to remain high until day 56.|||Lacks protease activity in vitro.|||Membrane|||Testis-specific (PubMed:23536369). Expressed by primary and secondary spermatocytes (PubMed:23536369). http://togogenome.org/gene/10090:Cnnm2 ^@ http://purl.uniprot.org/uniprot/Q3TWN3 ^@ Function|||Induction|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ACDP family.|||By low Mg(2+) concentration.|||Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+).|||Isoform 1 and isoform 2 may interact with each other.|||Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo.|||The N-terminus is cleaved within the endoplasmic reticulum. The signal peptidase complex seems to be involved in the processing, but the exact cleavage site has not been identified (PubMed:22399287).|||Widely expressed, with highest levels in kidney, lung, spleen and testis. In the kidney, predominantly expressed in the distal convoluted tubule and, at lower levels, in the connecting tubule (at protein level). http://togogenome.org/gene/10090:Sema6b ^@ http://purl.uniprot.org/uniprot/O54951|||http://purl.uniprot.org/uniprot/Q3UTK5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell membrane|||During development it is expressed in subregions of the nervous system and is particularly prominent in muscle (PubMed:9361278, PubMed:32169168). Expressed at embryonic day 18.5 dpc (PubMed:32169168).|||Functions as a cell surface repellent for mossy fibers of developping neurons in the hippocampus where it plays a role in axon guidance (PubMed:20484647). May function through the PLXNA4 receptor expressed by mossy cell axons (PubMed:20484647).|||Homodimer (PubMed:9361278). Binds specifically the SH3 domain of the protooncogene C-SRC (PubMed:9361278).|||In adulthood, it is expressed ubiquitously.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice lacking Sema6b are viable and fertile but display abnormal projection of hippocampal mossy fibers. http://togogenome.org/gene/10090:Sgpp2 ^@ http://purl.uniprot.org/uniprot/Q810K3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type 2 lipid phosphate phosphatase family.|||Developmentally regulated. Expression during kidney development increases around 8 fold from 11.5 dpc and adult. Highest expression is found in the ureteric bud.|||Endoplasmic reticulum membrane|||Has specific phosphohydrolase activity towards sphingoid base 1-phosphates. Has high phosphohydrolase activity against dihydrosphingosine-1-phosphate and sphingosine-1-phosphate (S1P) in vitro (Probable). Sphingosine-1-phosphate phosphatase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway (By similarity). May play a role in attenuating intracellular sphingosine 1-phosphate (S1P) signaling. May play a role in pro-inflammatory signaling (By similarity). Plays a role in the regulation of pancreatic islet beta-cell endoplasmic reticulum stress and proliferation (PubMed:27059959).|||Highly expressed in pancreatic islets. Expressed in lung, small interstince, colon, kideny and brain.|||Mutans are viable into the adulthod. They exhibit smaller pancreatic islets, defective beta-cell proliferation and decreased blood insulin levels after treatment with a high-fat diet (PubMed:27059959). Beta-cells show increased expression of proteins characteristic of the endoplasmic reticulum stress response (PubMed:27059959). http://togogenome.org/gene/10090:Vav2 ^@ http://purl.uniprot.org/uniprot/Q60992 ^@ Function|||PTM|||Subunit ^@ Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly.|||Interacts (via SH2 domains) with the phosphorylated form of EPHA2. Interacts with NEK3 and PRLR and this interaction is prolactin-dependent (By similarity). Interacts with SSX2IP.|||Phosphorylated on tyrosine residues in response to FGR activation. http://togogenome.org/gene/10090:Dpm1 ^@ http://purl.uniprot.org/uniprot/O70152 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 2 family.|||Binds 1 divalent metal cation.|||Component of the dolichol-phosphate mannose (DPM) synthase complex composed of DPM1, DPM2 and DPM3; within the complex, directly interacts with DPM3. This interaction may stabilize DPM1.|||Endoplasmic reticulum|||Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins; catalytic subunit of the dolichol-phosphate mannose (DPM) synthase complex. http://togogenome.org/gene/10090:Plac8l1 ^@ http://purl.uniprot.org/uniprot/Q08EJ0 ^@ Similarity ^@ Belongs to the cornifelin family. http://togogenome.org/gene/10090:Asf1b ^@ http://purl.uniprot.org/uniprot/Q9DAP7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ASF1 family.|||Expressed in early embryos and germ cells.|||Highly expressed in germ cells (PubMed:26850882). Restricted to premeiotic to meiotic stages during spermatogenesis (PubMed:12842904).|||Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly (PubMed:12842904, PubMed:17054786). Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly (By similarity). Also involved in the nuclear import of the histone H3-H4 dimer together with importin-4 (IPO4): specifically recognizes and binds newly synthesized histones with the monomethylation of H3 'Lys-9' (H3K9me1) and diacetylation at 'Lys-5' and 'Lys-12' of H4 (H4K5ac and H4K12ac) marks in the cytosol (By similarity). Does not participate in replication-independent nucleosome deposition which is mediated by ASF1A and HIRA (By similarity). Required for gonad development (PubMed:26850882).|||Interacts with histone H3 (including both histone H3.1 and H3.3) and histone H4 (By similarity). Interacts with the CHAF1A, CHAF1B and RBBP4 subunits of the CAF-1 complex (By similarity). Interacts with HAT1, NASP and TAF1 (By similarity). Interacts with CDAN1. Found in a cytosolic complex with CDAN1, ASF1A, IPO4 and histones H3.1 and H4 (By similarity). Interacts with CREBBP (By similarity).|||Mice are viable but display subfertility caused by altered gamete formation (PubMed:26850882). The timing of meiotic entry and the subsequent gonad development is more severely impaired in female than in male mice (PubMed:26850882). Increased perinatal lethality is also increased in the offspring of knockout females (PubMed:26850882).|||Nucleus|||Phosphorylated by TLK2 (By similarity). Phosphorylated by TLK1 (PubMed:17054786).|||cytosol http://togogenome.org/gene/10090:Iah1 ^@ http://purl.uniprot.org/uniprot/Q9DB29 ^@ Function|||Similarity ^@ Belongs to the 'GDSL' lipolytic enzyme family. IAH1 subfamily.|||Probable lipase. http://togogenome.org/gene/10090:Mfsd3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J004|||http://purl.uniprot.org/uniprot/Q5U419 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ After 24 hours of starvation, up-regulated in the brainstem and cerebellum and down-regulated in the hypothalamus (PubMed:27981419). Following 8 weeks of high-fat diet, down-regulated in the brainstem (PubMed:27981419).|||Belongs to the major facilitator superfamily.|||In brain, expressed in the cortex, striatum, hippocampus, hypothalamus, thalamus and cerebellum (at protein level) (PubMed:27981419). Widely expressed with highest levels in kidney and liver (PubMed:27981419).|||Membrane http://togogenome.org/gene/10090:Id3 ^@ http://purl.uniprot.org/uniprot/P41133|||http://purl.uniprot.org/uniprot/Q545W1 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By a variety of mitogenic agents in serum starved cells. Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain and heart with peak levels between CT16 and CT20 in SCN and between CT8 and CT12 in the heart.|||Cytoplasm|||Expressed by myoblasts (at protein level).|||Homodimer, and heterodimer with other HLH proteins. Interacts with CLOCK and BMAL1 (By similarity). Interacts with COPS5 and COPS7A. Interacts with IFI204. Interacts with GATA4 and NKX2-5. Interacts with ANKRD2; both proteins cooperate in myoblast differentiation.|||Nucleus|||Polyubiquitinated; which is favored by Ifi204 and leads to proteasomal degradation.|||Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Involved in myogenesis by inhibiting skeletal muscle and cardiac myocyte differentiation and promoting muscle precursor cells proliferation. Inhibits the binding of E2A-containing protein complexes to muscle creatine kinase E-box enhancer. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. http://togogenome.org/gene/10090:Golt1a ^@ http://purl.uniprot.org/uniprot/Q9DCQ3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GOT1 family.|||Golgi apparatus membrane|||May be involved in fusion of ER-derived transport vesicles with the Golgi complex. http://togogenome.org/gene/10090:Gimap5 ^@ http://purl.uniprot.org/uniprot/Q8BWF2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.|||Endosome membrane|||Expressed in thymus (in thymocytes), spleen (in splenocytes), lymph node and lung (PubMed:16509771). Highly expressed in T lymphocytes (PubMed:16509771, PubMed:21502331). Expressed in B cells and in distinct lineages of hematopoietic bone marrow cells, including natural killer, B, T, myeloid and erythroid lineages (PubMed:21502331). Expressed in liver endothelial cells (PubMed:33956074).|||Interacts with BAD, BAK1, BAX, BCL2, BCL2L1/Bcl-xL and BCL2L11/BimEL (PubMed:16509771, PubMed:21502331). The interaction with BAX is increased, when cells initiate apoptosis upon IL2 withdrawal (PubMed:16509771). Forms a complex with BCL2L1 or MCL1 and HSPA8/HSC70; the interaction between HSPA8 and BCL2L1 or MCL1 is impaired in the absence of GIMAP5 (PubMed:21502331). May interact (via N-terminus) with microtubules (By similarity).|||Knockout mice are born at the expected Mendelian rate, with a normal sex ratio, but have a median survival of only 15 weeks. They exhibit chronic hepatic hematopoiesis and, in later stages, show pronounced hepatocyte apoptosis, leading to lethal liver failure. Loss of GIMAP5 function impairs peripheral T-cell survival, imposes a complete block of natural killer (NK) and NK T-cell development (PubMed:18796632). Mutant mice show progressive multilineage failure of bone marrow and hematopoiesis. Compared with that of wild-type counterparts, the bone marrow contains more hematopoietic stem cells, but fewer lineage-committed hematopoietic progenitors (PubMed:21502331).|||Lysosome|||Lysosome membrane|||Plays a role in T lymphocyte development and the optimal generation of CD4/CD8 double-positive thymocytes (PubMed:16509771). Inhibitor of GSK3A. May act by sequestering GSK3A in cytoplasmic vesicles and impairing its translocation to the nucleus. Consequently, impairs GSK3A-dependent transcriptional program and regulation of the DNA damage response occurring during T cells proliferation (PubMed:29382851). Required for the survival of bone marrow hematopoietic stem cells, as well as of peripheral T cells, natural killer (NK) and NK T-cell development and the maintenance of normal liver function (PubMed:18796632, PubMed:21502331). May promote the survival of mature T lymphocytes upon cytokine withdrawal (PubMed:16509771). May regulate Ca(2+) homeostasis by modulating lysosomal Ca(2+) stores, preventing its accumulation in the absence of T cell activation (By similarity). May play a role in mitochondrial DNA segregation in hematopoietic tissues (PubMed:25808953). Is a regulator of liver endothelial cell homeostasis (PubMed:33956074).|||Up-regulated upon the maturation of CD4/CD8 double-positive to CD4 single-positive thymocytes.|||multivesicular body membrane http://togogenome.org/gene/10090:Trmt10a ^@ http://purl.uniprot.org/uniprot/Q8C1Z8 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily. TRM10 family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Interacts with tRNA.|||Nucleus|||S-adenosyl-L-methionine-dependent guanine N(1)-methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 (m1G9) in tRNAs. Probably not able to catalyze formation of N(1)-methyladenine at position 9 (m1A9) in tRNAs.|||nucleolus http://togogenome.org/gene/10090:Cyp2d9 ^@ http://purl.uniprot.org/uniprot/P11714|||http://purl.uniprot.org/uniprot/Q3UNW2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Rpl23a ^@ http://purl.uniprot.org/uniprot/P62751|||http://purl.uniprot.org/uniprot/Q5M9M5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL23 family.|||Citrullinated by PADI4.|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with LYAR and GNL2 (By similarity). Interacts with MDM2; this interaction may promote MDM2-mediated p53/TP53 polyubiquitination (By similarity). Directly interacts (via BIB domain) with IPO5, IPO7, KPNB1 and TNPO1; these interactions are involved in RPL23A nuclear import for the assembly of ribosomal subunits (By similarity). Interacts with IPO8 (By similarity).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Binds a specific region on the 26S rRNA (By similarity). May promote p53/TP53 degradation possibly through the stimulation of MDM2-mediated TP53 polyubiquitination (By similarity).|||Cytoplasm|||N-terminus is methylated by METTL11A/NTM1.|||Nucleus|||The N-terminal beta-like import receptor binding (BIB) domain mediates interaction with IPO5, IPO7, KPNB1 and TNPO1. http://togogenome.org/gene/10090:Vmn1r14 ^@ http://purl.uniprot.org/uniprot/H3BJ46 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cdk2ap2 ^@ http://purl.uniprot.org/uniprot/Q9CPY4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity). Inhibits cell cycle G1/S phase transition by repressing CDK2 expression and activation; represses CDK2 activation by inhibiting its interaction with cyclin E and A (By similarity). Plays a role in regulating the self-renewal of embryonic stem cells (ESCs) and in maintaining cell survival during terminal differentiation of ESCs (PubMed:22548356). Regulates microtubule organization of metaphase II oocytes (PubMed:12944431).|||Belongs to the CDK2AP family.|||Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (By similarity). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (By similarity). Interacts with CDK2AP1 (By similarity). Interacts with CDK2 (By similarity). Interacts with MAPK1 (PubMed:12944431).|||Cytoplasm|||Nucleus|||Oocytes (at protein level).|||Phosphorylated by MAPK1 and CDK2. http://togogenome.org/gene/10090:Tmie ^@ http://purl.uniprot.org/uniprot/Q8K467 ^@ Developmental Stage|||Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Defects in Tmie are the cause of the spinner mutant strain phenotype (sr). This disorder results in hearing loss and vestibular dysfunction due to neuroepithelial defects in the inner ear. It is recognized by behavioral dysfunction, including bidirectional circling and head shaking. Auditory function in spinner mice is found to be reduced, based upon the lack of a startle reflex to sound at any age. Breeding experiments indicated that these defects are inherited in an autosomal recessive fashion. The postnatal defects present in the cochleae of sr/sr mice suggest a requirement for Tmie during maturation of sensory cells, including the normal development or maintenance of stereocilia bundles.|||Expressed in brain, kidney, liver, lung and cochlea.|||Interacts with TOMT.|||Membrane|||Required for normal postnatal maturation of sensory hair cells in the cochlea, including correct development of stereocilia bundles.|||Unknown. The protein may play some role in a cellular membrane location. May reside within an internal membrane compartment and function in pathways such as those involved in protein and/or vesicle trafficking. Alternatively, the mature protein may be localized in the plasma membrane and serve as a site of interaction for other molecules through its highly charged C-terminal domain. http://togogenome.org/gene/10090:Ttc4 ^@ http://purl.uniprot.org/uniprot/Q3UZC4|||http://purl.uniprot.org/uniprot/Q8R3H9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TTC4 family.|||Cytoplasm|||Expressed at high levels in the heart, testis, kidney, brain and tongue (PubMed:19390865). Expressed at low levels in the stomach, lung and liver (PubMed:19390865).|||Interacts (via TPR repeats) with HSP90AB1 (By similarity). Interacts with HSPA8, CDC6 and TBK1 (By similarity). Interacts with isoform 1 and isoform 3 of MSL1 (PubMed:17335777).|||May act as a co-chaperone for HSP90AB1 (By similarity).|||Nucleus|||nucleoplasm http://togogenome.org/gene/10090:Lcn5 ^@ http://purl.uniprot.org/uniprot/A2AJB7 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 2 different forms with differently processed N-termini exist.|||Associates with spermatozoa in the epididymal fluid but does not bind tightly to them. Binds both all-trans and 13-cis retinoic acid. May act as a retinoid carrier protein which is required for epididymal function and/or sperm maturation.|||Belongs to the calycin superfamily. Lipocalin family.|||Down-regulated to 11% of control levels 5 days after castration and is not detectable by 20 days (at protein level). Levels are partially restored by subsequent testosterone treatment.|||Epididymal fluid of the caudal and corpus regions (at protein level).|||Secreted http://togogenome.org/gene/10090:Zwilch ^@ http://purl.uniprot.org/uniprot/G3X9Z0|||http://purl.uniprot.org/uniprot/Q8R060 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZWILCH family.|||Component of the RZZ complex composed of KNTC1/ROD, ZW10 and ZWILCH; in the complex interacts directly with KNTC1/ROD (By similarity).|||Component of the RZZ complex.|||Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (By similarity).|||Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex.|||kinetochore http://togogenome.org/gene/10090:Snx21 ^@ http://purl.uniprot.org/uniprot/Q149Q9|||http://purl.uniprot.org/uniprot/Q3UR97 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Binds to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)) and phosphatidylinositol 4,5-bisphosphate (PubMed:25882846). May be involved in several stages of intracellular trafficking.|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Membrane|||Monomer.|||The PX domain mediates specific binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)). http://togogenome.org/gene/10090:Atp2b3 ^@ http://purl.uniprot.org/uniprot/A2ALL9|||http://purl.uniprot.org/uniprot/Q0VF55|||http://purl.uniprot.org/uniprot/Q8C048 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.|||Catalyzes the hydrolysis of ATP coupled with the transport of calcium.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Vmn1r160 ^@ http://purl.uniprot.org/uniprot/E9Q346 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sbspon ^@ http://purl.uniprot.org/uniprot/Q3UPR9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the thrombospondin family.|||extracellular matrix http://togogenome.org/gene/10090:Rab3gap2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YWM5|||http://purl.uniprot.org/uniprot/E9QKE4|||http://purl.uniprot.org/uniprot/Q8BMG7 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Rab3-GAP regulatory subunit family.|||Cytoplasm|||Endoplasmic reticulum|||Regulatory subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of Rab3gap1 and Rab3gap2, which has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide exchange factor (GEF) activity towards RAB18 (By similarity). As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP (By similarity). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones (By similarity). The Rab3GAP complex, acts as a GEF for RAB18 by promoting the conversion of inactive RAB18-GDP to the active form RAB18-GTP (By similarity). Required for recruiting and activating RAB18 at the endoplasmic reticulum (ER) membrane where it maintains proper ER structure (By similarity). Required for normal eye and brain development (By similarity). May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters (By similarity).|||The Rab3 GTPase-activating complex is a heterodimer composed of Rab3gap1 and Rab3gap2 (By similarity). The Rab3 GTPase-activating complex interacts with DMXL2 (By similarity). Interacts with LMAN1 (By similarity).|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:H2al1e ^@ http://purl.uniprot.org/uniprot/Q810S6 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Car11 ^@ http://purl.uniprot.org/uniprot/O70354|||http://purl.uniprot.org/uniprot/Q541E9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-carbonic anhydrase family.|||Does not have a catalytic activity.|||Secreted http://togogenome.org/gene/10090:Ubap1 ^@ http://purl.uniprot.org/uniprot/Q8BH48 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with PTPN23. Interacts (via UBA domains) with ubiquitinated proteins.|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process (PubMed:31203368). Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) (By similarity). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2 (PubMed:31203368).|||Endosome|||Lethality by postnatal day 14 (PubMed:31203368). Conditional deletion in neurons impairs endosomal ubiquitin processing and promotes neurodegeneration (PubMed:31203368).|||The UMA domain mediates association with the ESCRT-I complex.|||Ubiquitous. Highly expressed in heart, liver, brain, kidney, spleen, skeletal muscle, stomach, testis and lung.|||cytosol http://togogenome.org/gene/10090:Tbx15 ^@ http://purl.uniprot.org/uniprot/O70306 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Can form a heterodimer with TBX18.|||Expressed during limb development, first in the mesenchyme of the early limb bud, then during early endochondral bone development in prehypertrophic chondrocytes of cartilaginous templates. Expression is also found in mesenchymal precursor cells and prehypertrophic chondrocytes, respectively, during development of skeletal elements of the vertebral column and the head.|||Mice show a general reduction of bone size and changes of bone shape. In the forelimb skeleton, the scapula lacks the central region of the blade. Cartilaginous templates are already reduced in size and show a transient delay in ossification in mutant embryos. Mice show a significantly reduced proliferation of prehypertrophic chondrocytes as well as of mesenchymal precursor cells.|||Nucleus|||Probable transcriptional regulator involved in the development of the skeleton of the limb, vertebral column and head. Acts by controlling the number of mesenchymal precursor cells and chondrocytes. http://togogenome.org/gene/10090:Shbg ^@ http://purl.uniprot.org/uniprot/A0A158SIS9|||http://purl.uniprot.org/uniprot/P97497 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration (By similarity).|||Homodimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Rxrb ^@ http://purl.uniprot.org/uniprot/P28704|||http://purl.uniprot.org/uniprot/Q3TWJ1|||http://purl.uniprot.org/uniprot/Q8VCR0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Homodimer (in vitro). Heterodimer with other retinoic acid receptor family members. Binds DNA preferentially as a RAR/RXR heterodimer. Interacts with NR1H3 (By similarity). Interacts with AKAP13 (PubMed:20139090).|||Homodimer. Heterodimer; with a rar molecule.|||In all tissues tested, including brain, thymus, spleen and liver.|||Nucleus|||Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes.|||Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE). http://togogenome.org/gene/10090:Sesn2 ^@ http://purl.uniprot.org/uniprot/P58043 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sestrin family.|||Cytoplasm|||Detected in heart, liver and skeletal muscles (at protein level).|||Functions as an intracellular leucine sensor that negatively regulates the mTORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25259925). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents mTORC1 signaling (PubMed:18692468, PubMed:25259925). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:18692468, PubMed:25259925). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses (By similarity). May negatively regulate protein translation in response to endoplasmic reticulum stress, via mTORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (By similarity). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1. However, this could not be confirmed (By similarity).|||Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (By similarity). Conveys leucine availability via direct interaction with SEH1L and WDR24 components of the GATOR2 complex (By similarity). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). May interact with the TORC2 complex (PubMed:25377878). Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the degradation of KEAP1 (PubMed:25040165). May also associate with the complex composed of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to regulate TORC1 signaling (PubMed:18692468). May interact with PRDX1 (By similarity).|||Phosphorylated by ULK1 at multiple sites.|||Sesn2 knockout mice are fully viable and do not display any overt developmental abnormalities. When kept on high fat diet, they display higher insulin resistance and glucose intolerance (PubMed:22958918). The oxidative stress induced by acute lipogenesis upon refeeding results in increased liver damages in the Sesn2 knockout mice. Any condition, like obesity, that triggers chronic or acute endoplasmic reticulum stresses have the same consequences in these mice and can lead to liver fibrosis (PubMed:23274085, PubMed:24947615). Sesn2 and Sesn3 double knockout mice display insulin resistance and glucose intolerance (PubMed:22958918). Triple knockout mice lacking Sesn1, Sesn2 and Sesn3 do not display an embryonic lethal phenotype since they are born at an expected Mendelian ratio. Moreover, they are not distinguishable from their wild-type littermates. However, their survival at 10 days is dramatically affected. This is associated with a constitutive activation of TORC1 signaling in the liver, heart and skeletal muscle during postnatal fasting, that occurs between birth and suckling (PubMed:25259925).|||The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.|||The N-terminal domain has an alkylhydroperoxide reductase activity.|||Ubiquitinated at Lys-175 by RNF167 via 'Lys-63'-linked polyubiquitination in response to leucine deprivation: ubiquitination promotes SESN2-interaction with the GATOR2 complex, leading to inhibit the TORC1 signaling pathway. Deubiquitinated at Lys-175 by STAMBPL1, promoting the TORC1 signaling pathway. Ubiquitinated by RNF186; ubiquitination mediates proteasomal degradation.|||Up-regulated by treatments inducing endoplasmic reticulum stress. http://togogenome.org/gene/10090:Or4c10b ^@ http://purl.uniprot.org/uniprot/Q8VGP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc4a9 ^@ http://purl.uniprot.org/uniprot/A0A494BA31|||http://purl.uniprot.org/uniprot/A0A494BAI0|||http://purl.uniprot.org/uniprot/A0A494BBC3|||http://purl.uniprot.org/uniprot/E9PUP3|||http://purl.uniprot.org/uniprot/Q14CH2|||http://purl.uniprot.org/uniprot/Q14DJ1|||http://purl.uniprot.org/uniprot/Q3UQE1|||http://purl.uniprot.org/uniprot/Q8BUG8 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Chambrey et al. shows that the transport mechanism differs in renal cells and suggests that SLC4A9 is a Na(+)/HCO3(-) cotransporter in mouse kidney beta-intercalated cells (PubMed:23610411). However the stoichiometry is not defined and the role of chloride ions is not clear.|||Cl(-)/HCO3(-) exchanger activity is substantially increased in response to 5 uM isoproterenol (PubMed:34585968). Cl(-)/HCO3(-) exchanger activity is increased by both forskolin and coexpression with the catalytic subunit alpha of PKA (PubMed:34585968).|||Electroneutral Cl(-)/HCO3(-) antiporter that favors chloride ion entry and efflux of hydrogencarbonate and sodium ion across the basolateral membrane and may participate in salivary secretion (PubMed:25745107, PubMed:27114614). Also mediates Cl(-)/HCO3(-) exchange activity in the presence of K(+) as well as Cs(+), Li(+), and Rb(+) (PubMed:27114614). Does not contribute to Cl(-)/HCO3(-) exchanger in the apical membrane of the upper villous epithelium (PubMed:17170027).|||Expressed in submandibular gland (SMG) duct and cortical collecting duct (CCD) of kidney (PubMed:12225984, PubMed:23610411). Lower expressed in duodenal villi (PubMed:17170027).|||Homozygous mice lacking the Slc4a9 gene have no obvious phenotypical abnormalities.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lateral cell membrane|||Membrane http://togogenome.org/gene/10090:Ercc4 ^@ http://purl.uniprot.org/uniprot/Q9QZD4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-912 by KAT5 promotes interaction with ERCC1 by disrupting a salt bridge between Asp-908 and Lys-912, thereby exposing a second binding site for ERCC1 (By similarity). Deacetylated by SIRT1 (By similarity).|||Belongs to the XPF family.|||Catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair, and which is essential for nucleotide excision repair (NER) and interstrand cross-link (ICL) repair.|||Chromosome|||Heterodimer composed of ERCC1 and ERCC4/XPF. Interacts with SLX4/BTBD12; this interaction is direct and links the ERCC1-ERCC4/XPF complex to SLX4, which may coordinate the action of the structure-specific endonuclease during DNA repair.|||Nucleus http://togogenome.org/gene/10090:Mdm2 ^@ http://purl.uniprot.org/uniprot/P23804 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitination leads to proteasomal degradation; resulting in p53/TP53 activation it may be regulated by SFN. Also ubiquitinated by TRIM13. Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7 leading to its stabilization (By similarity).|||Belongs to the MDM2/MDM4 family.|||By UV light (PubMed:10075719). Down-regulated by NPAS4 (PubMed:25088421).|||Cytoplasm|||Does not bind to p53. Can be produced by alternative initiation at Met-50 of isoform Mdm2-p90, but is produced more efficiently by alternative splicing.|||E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:15195100, PubMed:21804542). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity). Also acts as a ubiquitin ligase E3 toward itself, ARRB1 and ARBB2 (PubMed:11588219). Permits the nuclear export of p53/TP53 (By similarity). Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein (By similarity). Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation (By similarity). Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53 (By similarity). Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways (By similarity). Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus (By similarity). Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (By similarity). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (PubMed:25088421). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (PubMed:14642282). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903).|||Interacts with p53/TP53, TP73/p73, RBL5 and RP11. Binds specifically to RNA. Can interact with RB1, E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with p53/TP53 and WWOX. Interacts with CDKN2AIP, RFWD3, USP7, PYHIN1 and RBBP6. Interacts with ARRB1 and ARRB2. Interacts with PSMA3. Found in a trimeric complex with MDM2, MDM4 and USP2. Interacts with USP2 (via N-terminus and C-terminus). Interacts with MDM4. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts directly with DAXX and USP7. Interacts (via C-terminus) with RASSF1 isoform A (via N-terminus); the interaction is independent of TP53. Interacts with APEX1; leading to its ubiquitination and degradation. Interacts with RYBP; this inhibits ubiquitination of TP53. Identified in a complex with RYBP and p53/TP53. Also a component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53 stabilization and activity. Binds directly both p53/TP53 and TRIM28. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor responses with DNA damage. Interacts directly with both TRIM28 and ERBB4 in the complex. Interacts with DYRK2. Interacts with IGF1R. Interacts with TRIM13; the interaction ubiquitinates MDM2 leading to its proteasomal degradation. Interacts with SNAI1; this interaction promotes SNAI1 ubiquitination. Interacts with NOTCH1 (via intracellular domain). Interacts with FHIT. Interacts with RFFL and RNF34; the interaction stabilizes MDM2. Interacts with CDK5RAP3 and CDKN2A/ARF; form a ternary complex involved in regulation of p53/TP53. Interacts with MTA1 (By similarity). Interacts with AARB2 (PubMed:11588219). Interacts with MTBP (PubMed:10906133). Interacts with PML (PubMed:15195100). Interacts with TBRG1 (PubMed:17110379). Interacts with the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11; the interaction is direct occurs in the nucleoplasm and negatively regulates MDM2-mediated TP53 ubiquitination and degradation (PubMed:15195100, PubMed:21804542). Interacts with ADGRB1; the interaction results in inhibition of MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity (PubMed:25751059). Interacts with RPL23A; this interaction may promote p53/TP53 polyubiquitination (By similarity). Interacts with NDUFS1 (PubMed:30879903). Interacts with MORN3; the interaction enhances the ubiquitination of p53/TP53 (By similarity).|||Loss of Dlg4 ubiquitination.|||Nucleus|||Phosphorylation on Ser-163 by SGK1 activates ubiquitination of p53/TP53. Phosphorylated at multiple sites near the RING domain by ATM upon DNA damage; this prevents oligomerization and E3 ligase processivity and impedes constitutive p53/TP53 degradation (By similarity).|||Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself.|||Ubiquitously expressed at low-level throughout embryo development and in adult tissues. MDM2-p90 is much more abundant than MDM2-p76 in testis, brain, heart, and kidney, but in the thymus, spleen, and intestine, the levels of the MDM2 proteins are roughly equivalent.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Nmnat3 ^@ http://purl.uniprot.org/uniprot/Q99JR6 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD) (By similarity).|||Belongs to the eukaryotic NMN adenylyltransferase family.|||Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can also use GTP and ITP as nucleotide donors. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, can use NAD(+), NADH, NaAD, nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide (NGD) as substrates. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (By similarity). Protects against axonal degeneration following injury.|||Divalent metal cations. Mg(2+) confers the highest activity.|||Expressed throughout development and in adulthood.|||Homotetramer.|||Mitochondrion http://togogenome.org/gene/10090:Tm6sf2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J9|||http://purl.uniprot.org/uniprot/E9QM19|||http://purl.uniprot.org/uniprot/Q8R1J1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TM6SF family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Highly expressed in the liver at both the mRNA and protein levels.|||Membrane|||Regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. May function as sterol isomerase. http://togogenome.org/gene/10090:Chp2 ^@ http://purl.uniprot.org/uniprot/Q9D869 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calcineurin regulatory subunit family. CHP subfamily.|||Cell membrane|||Cytoplasm|||Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Binds to and activates SLC9A1/NHE1 in a serum-independent manner, thus increasing pH and protecting cells from serum deprivation-induced death. Also plays a role in the regulation of cell proliferation and tumor growth by increasing the phosphatase activity of PPP3CA in a calcium-dependent manner. Activator of the calcineurin/NFAT signaling pathway. Involved in the cytoplasmic translocation of the transcription factor NFATC3 to the nucleus (By similarity).|||Interacts with PPP3CA. Interacts with SLC9A1/NHE1; the interaction occurs in a calcium-dependent manner. Interacts with SLC9A1/NHE1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Aplp1 ^@ http://purl.uniprot.org/uniprot/Q03157|||http://purl.uniprot.org/uniprot/Q3TUB1 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APP family.|||Binds zinc and copper in the extracellular domain. Zinc-binding increases heparin binding. No Cu(2+) reducing activity with copper-binding.|||Cell membrane|||Cytoplasm|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding. Couples to JIP signal transduction through C-terminal binding. May interact with cellular G-protein signaling pathways. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I.|||Membrane|||Monomer and homodimer. Heparin binding promotes homodimerization. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB and APBA family members, MAPK8IP1 and DAB1 (By similarity). Binding to Dab1 inhibits its serine phosphorylation. Interacts with CPEB1. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif) with DAB1.|||N- and O-glycosylated.|||Proteolytically cleaved by caspases during neuronal apoptosis. Cleaved, in vitro, at Asp-624 by caspase-3 (By similarity).|||The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The NPXY site is also involved in clathrin-mediated endocytosis.|||The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis. http://togogenome.org/gene/10090:Yeats2 ^@ http://purl.uniprot.org/uniprot/B9EKJ4|||http://purl.uniprot.org/uniprot/Q3TUF7 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors.|||Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, SGF29 and DR1.|||Nucleus|||The YEATS domain specifically recognizes and binds crotonylated histones.|||The sequence differs from that shown because it is derived from pre-RNA. http://togogenome.org/gene/10090:Or1e22 ^@ http://purl.uniprot.org/uniprot/Q5SSP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp768 ^@ http://purl.uniprot.org/uniprot/Q8R0T2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds to mammalian-wide interspersed repeat (MIRs) sequences in euchromatin and promoter regions of genes at the consensus sequence 5'-GCTGTGTG-[N20]-CCTCTCTG-3', consisting of two anchor regions connected by a linker region; the linker region probably does not contribute to the binding specificity (By similarity). Required for cell homeostasis (By similarity). May be involved in transcriptional regulation (Probable).|||Chromosome|||Interacts (via zinc-finger domains) with TP53 (via N-terminus); interaction might be facilitated by TP53 oligomerization state (By similarity). Interacts with ELP3 (By similarity).|||May be phosphorylated at residue 'Ser-5' of the tandem heptapeptide repeats in the N-terminus (By similarity). Phosphorylation might be increased upon RAS pathway activation and negatively regulate protein stability (By similarity).|||Nucleus http://togogenome.org/gene/10090:Xkr4 ^@ http://purl.uniprot.org/uniprot/Q5GH67 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the XK family.|||Cell membrane|||Highly expressed in expressed in the brain; weakly expressed in the spleen, thymus, uterus, blood vessels and fetus.|||Homodimer; homodimerization takes place upon caspase cleavage (PubMed:33725486). Interacts with the processed C-terminus of XRCC4 (protein XRCC4, C-terminus); interaction promotes the phospholipid scramblase activity (PubMed:33725486).|||Homodimerizes upon caspase cleavage (PubMed:33725486). Phospholipid scramblase activity is activated following interaction with the processed C-terminus of XRCC4 (protein XRCC4, C-terminus) (PubMed:33725486).|||Phospholipid scramblase activity is activated upon caspase cleavage to generate the XK-related protein 4, processed form (PubMed:25231987, PubMed:33725486). Does not act prior the onset of apoptosis (PubMed:25231987).|||Phospholipid scramblase that promotes phosphatidylserine exposure on apoptotic cell surface (PubMed:25231987, PubMed:33725486). Phosphatidylserine is a specific marker only present at the surface of apoptotic cells and acts as a specific signal for engulfment (PubMed:25231987, PubMed:33725486).|||Undergoes proteolytic processing by caspase-3 (CASP3), caspase-6 (CASP6) and caspase-7 (CASP7) to generate the XK-related protein 4, processed form, leading to its activation. http://togogenome.org/gene/10090:Kcnmb1 ^@ http://purl.uniprot.org/uniprot/Q5SQK1|||http://purl.uniprot.org/uniprot/Q8CAE3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the KCNMB (TC 8.A.14.1) family.|||Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB1 subfamily.|||Expressed in many tissues containing smooth muscles. In brain and heart, it is not expressed except in the vasculature, such as cerebral arteries, aorta and corona arteries.|||Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB per KCNMA1 tetramer.|||Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB1 per KCNMA1 tetramer (By similarity).|||Membrane|||N-glycosylated.|||Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity.|||Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate. http://togogenome.org/gene/10090:Tpm3 ^@ http://purl.uniprot.org/uniprot/D3Z6I8|||http://purl.uniprot.org/uniprot/E9Q5J9|||http://purl.uniprot.org/uniprot/P21107|||http://purl.uniprot.org/uniprot/Q58E70|||http://purl.uniprot.org/uniprot/Q8C7C3|||http://purl.uniprot.org/uniprot/Q8K0Z5 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tropomyosin family.|||Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.|||Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain. Interacts with TMOD1.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.|||cytoskeleton http://togogenome.org/gene/10090:Adam17 ^@ http://purl.uniprot.org/uniprot/E9PXU2|||http://purl.uniprot.org/uniprot/Q9Z0F8 ^@ Activity Regulation|||Caution|||Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Cell membrane|||Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Plays a role in the proteolytic processing of ACE2 (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:10799547, PubMed:11108241). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (PubMed:10882063). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (PubMed:12907434). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (PubMed:17245433). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (By similarity). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells.|||Inhibited by metalloproteinase inhibitor 3 (TIMP-3), but not by TIMP-1, TIMP-2 and TIMP-4.|||Interacts with MAD2L1, MAPK14 and MUC1. Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2. Interacts with FRMD8 via its interaction with iRhom1/RHBDF1 and iRhom2/RHBDF2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR.|||Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-822 but decreases phosphorylation of Ser-794. Phosphorylation at Thr-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding (By similarity).|||Secreted|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||Ubiquitously expressed. Expressed at highest levels in heart, liver, skeletal muscle, kidney and testes. Expressed at lower levels in brain, spleen and lung. http://togogenome.org/gene/10090:Tmem45a ^@ http://purl.uniprot.org/uniprot/Q8BFU6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Membrane http://togogenome.org/gene/10090:Dpysl3 ^@ http://purl.uniprot.org/uniprot/E9PWE8|||http://purl.uniprot.org/uniprot/Q3TT92|||http://purl.uniprot.org/uniprot/Q62188 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.|||Cytoplasm|||Homotetramer, and heterotetramer with CRMP1, DPYSL2, DPYSL4 or DPYSL5. Interacts with synaptic vesicle protein 2 and SH3A domain of intersectin (By similarity). Interacts with FLNA (By similarity).|||Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.|||Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration (By similarity).|||Phosphorylation on Ser-522 by DYRK2 promotes subsequent phosphorylation on Thr-509, Thr-514 and Ser-518 by GSK3.|||growth cone http://togogenome.org/gene/10090:Trim35 ^@ http://purl.uniprot.org/uniprot/A0A0R4J031|||http://purl.uniprot.org/uniprot/Q8C006 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc expression was detected in branchial arches 1 and 2 and the fronto-nasal process, limb buds, spinal cord, and dorsal root ganglia. At 12.0 dpc expression was detected primarily in the limbs and transiently in the developing eye. By 13.5 dpc, expression in the limb was restricted to thetelencephalic region of forebrain.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||Deletion mutants are more sensitive to viral infections with a dramatically increased viral load.|||E3 ubiquitin-protein ligase that participates in multiple biological processes including cell death, glucose metabolism, and in particular, the innate immune response (By similarity) (PubMed:32562145). Mediates 'Lys-63'-linked polyubiquitination of TRAF3 thereby promoting type I interferon production via RIG-I signaling pathway. Can also catalyze 'Lys-48'-linked polyubiquitination and proteasomal degradation of viral proteins such as influenza virus PB2. Acts as a negative feedback regulator of TLR7- and TLR9-triggered signaling. Mechanistically, promotes the 'Lys-48'-linked ubiquitination of IRF7 and induces its degradation via a proteasome-dependent pathway. Reduces FGFR1-dependent tyrosine phosphorylation of PKM, inhibiting PKM-dependent lactate production, glucose metabolism, and cell growth (By similarity).|||Induced by macrophage colony-stimulating factor in murine peritoneal and bone marrow macrophages.|||Interacts with PKM isoform M2, but not isoform M1; this interaction may compete with that between PKM and FGFR1, and hence reduces FGFR1-dependent tyrosine phosphorylation of PKM. Interacts with IRF7; this interaction promotes IRF7 proteasomal degradation. Interacts with TRAF3; this interaction promotes TRAF3 activation.|||Nucleus|||The RING finger domain and the coiled-coil region are required for the apoptosis-inducing activity.|||Widely expressed. Highly expressed in brain, heart, kidney, spleen, skeletal muscle, lung and thymus. Lower expression found in stomach, large intestine and bone marrow. http://togogenome.org/gene/10090:Lao1 ^@ http://purl.uniprot.org/uniprot/B1ARV3 ^@ Similarity ^@ Belongs to the flavin monoamine oxidase family. http://togogenome.org/gene/10090:Cyp4f16 ^@ http://purl.uniprot.org/uniprot/Q99N17 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Stmn3 ^@ http://purl.uniprot.org/uniprot/O70166|||http://purl.uniprot.org/uniprot/Q545T6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the stathmin family.|||Exhibits microtubule-destabilizing activity, which is antagonized by STAT3.|||Golgi apparatus|||Interacts with STAT3. Interacts with CLU (secreted form); this interaction may act as an important modulator during neuronal differentiation (By similarity).|||N-terminal palmitoylation promotes specific anchoring to the cytosolic leaflet of Golgi membranes and subsequent vesicular trafficking along dendrites and axons. Neuronal Stathmins are substrates for palmitoyltransferases ZDHHC3, ZDHHC7 and ZDHHC15 (By similarity).|||Neuron specific.|||axon|||cytosol|||growth cone http://togogenome.org/gene/10090:Vps37b ^@ http://purl.uniprot.org/uniprot/Q8R0J7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS37 family.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101, VPS28, MVB12A and MVB12B. Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with CEP55. Interacts with IST1 (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation (By similarity).|||Late endosome membrane http://togogenome.org/gene/10090:Wdr12 ^@ http://purl.uniprot.org/uniprot/Q4V9X1|||http://purl.uniprot.org/uniprot/Q9JJA4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat WDR12/YTM1 family.|||Component of the PeBoW complex, composed of BOP1, PES1 and WDR12. The complex is held together by BOP1, which interacts with PES1 via its N-terminal domain and with WDR12 via a high-affinity interaction between the seven-bladed beta-propeller domains of the 2 proteins. The PeBoW complex associates with the 66S pre-ribosome. Interacts (via UBL domain) with MDN1 (via VWFA/MIDAS domain).|||Component of the PeBoW complex, composed of BOP1, PES1 and WDR12. Within the PeBoW complex BOP1 interacts directly with PES1 and WDR12. The PeBoW complex also associates with the 66S pre-ribosome.|||Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Csf2rb2 ^@ http://purl.uniprot.org/uniprot/P26954 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||Heterodimer of an alpha and a beta subunit.|||In mouse, there are two classes of high-affinity IL3 receptors. One contains this IL3-specific beta subunit and the other contains the beta subunit also shared by high-affinity IL5 and GM-CSF receptors.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Kifc5b ^@ http://purl.uniprot.org/uniprot/E9PUA5|||http://purl.uniprot.org/uniprot/Q9QWT9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. NCD subfamily.|||Binds NUBP1 and NUBP2 (PubMed:16638812). Interacts with PPP1R42 (PubMed:18237440).|||Centrosome amplification as well as multipolar spindles. Cells overexpressing Kifc1 show a single microtubule aster and growth arrest in prometaphase.|||Early endosome|||Highly expressed in 14 dpc embryos, spleen and NIH3T3 cells. Also expressed in testis, brain, lung, kidney and cultured astrocytes. Very low levels in skeletal muscle and heart.|||Highly expressed in hippocampus of 13 dpc embryos declining to low levels by 18 dpc and to undetectable levels in juvenile and adult hippocampus.|||Minus end-directed microtubule-dependent motor required for bipolar spindle formation (PubMed:16638812). May contribute to movement of early endocytic vesicles (PubMed:17360972). Regulates cilium formation and structure (PubMed:23807208).|||Nucleus|||Purified early endocytic vesicles bind minus end-directed Kifc1 as well as plus end-directed Kif5b. Addition of anti-Kifc1 antibodies leads to a decrease in minus end-directed vesicle motility in vitro.|||centrosome|||spindle http://togogenome.org/gene/10090:Zfp367 ^@ http://purl.uniprot.org/uniprot/Q0VDT2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in bone marrow and ovary.|||Highly expressed in fetal erythroid tissue. Lower expression in yolk sac.|||Nucleus|||Transcriptional activator. Isoform 1 may be involved in transcriptional activation of erythroid genes (By similarity). http://togogenome.org/gene/10090:Atp6v1b2 ^@ http://purl.uniprot.org/uniprot/P62814 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ATPase alpha/beta chains family.|||Cytoplasm|||Kidney; found in early distal nephron, encompassing thick ascending limbs and distal convoluted tubules and in the alpha-intercalated cells of the cortical collecting ducts (at protein level) (PubMed:16174750, PubMed:29993276, PubMed:17898041, PubMed:15013950). Expressed in epididymal clear cells (at protein level) (PubMed:15013950). Mainly expressed in the organ of Corti and spiral ganglion neurons, in both the early postnatal cochlea (P2) and the adult cochlea (P30) (PubMed:24913193).|||Melanosome|||Morpholino knockdown in the whole cochlea, especially in hair cells and spiral ganglion neurons causes a dose-dependent hearing loss.|||Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:17898041). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). In renal intercalated cells, can partially compensate the lack of ATP6V1B1 and mediate secretion of protons (H+) into the urine under base-line conditions but not in conditions of acid load (PubMed:17898041).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity).|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Lpcat2b ^@ http://purl.uniprot.org/uniprot/B2RT16|||http://purl.uniprot.org/uniprot/Q9D5U0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Membrane|||Probable acetyltransferase.|||The HXXXXD motif is essential for acyltransferase activity. http://togogenome.org/gene/10090:Tmsb10 ^@ http://purl.uniprot.org/uniprot/A6H6H4|||http://purl.uniprot.org/uniprot/Q6ZWY8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thymosin beta family.|||Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization (By similarity).|||Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Slc27a5 ^@ http://purl.uniprot.org/uniprot/Q4LDG0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Cell membrane|||Endoplasmic reticulum membrane|||Liver-specific (at protein level) (PubMed:16618416, PubMed:9642112). In liver expressed in a periportal distribution (PubMed:11980911).|||Mediates the import of long-chain fatty acids (LCFA) by facilitating their transport across cell membranes (PubMed:16618416). Also catalyzes the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates (By similarity). Mainly functions as a bile acyl-CoA synthetase catalyzing the activation of bile acids via ATP-dependent formation of bile acid CoA thioesters which is necessary for their subsequent conjugation with glycine or taurine (PubMed:16618417). Both primary bile acids (cholic acid and chenodeoxycholic acid) and secondary bile acids (deoxycholic acid and lithocholic acid) are the principal substrates (By similarity). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate ((25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate or THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol (By similarity). Plays an important role in hepatic fatty acid uptake and bile acid reconjugation and recycling but not in de novo synthesis of bile acids (PubMed:16618416, PubMed:16618417).|||Mice exhibit a severe bile acid conjugation defect (PubMed:16618417). Display a significant reduction in both liver lipid uptake and content and show a redistribution of lipids away from the liver to other tissues (PubMed:16618416). Hepatocytes show significantly reduced long-chain fatty acids (LCFA) uptake (PubMed:16618416).|||Microsome http://togogenome.org/gene/10090:Scd2 ^@ http://purl.uniprot.org/uniprot/P13011 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family.|||Detected in brain and skin (PubMed:10545940, PubMed:11161812, PubMed:16118274). Highly expressed in brain, and detected at low levels in heart, stomach, lung and testis (PubMed:11161812, PubMed:12815040). Detected both in dermis and epidermis (PubMed:16118274).|||Endoplasmic reticulum membrane|||Expected to bind 2 Fe(2+) ions per subunit.|||Highly expressed during embryonic development and during the first three weeks after birth. Expression is low in adults.|||Microsome membrane|||Mutant mice are born at the expected Mendelian rate. Neonates are smaller than wild-type and present high mortality, ranging from 70 to 100%, depending on the genetic background. Neonates display a shiny skin, but after a few hours their skin appears dry and cracked. The permeability barrier function of their skin is impaired, leading to rapid weight loss due to dehydration. Their epidermis has decreased levels of cholesterol esters, triglycerides, acylceramide, and glucosylacylceramide containing unsaturated fatty acids. In mutant neonates, triglyceride levels in liver and blood plasma are reduced by half, due to strongly reduced levels of stearoyl-CoA desaturase activity in the liver and strongly reduced levels of triglyceride biosynthesis. In contrast, the levels of stearoyl-CoA desaturase activity are normal in adult mice deficient for Scd2. Adult mice display kinked tails.|||Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates (PubMed:16443825). Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA (PubMed:16443825). Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids (PubMed:16443825). Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides, especially during embryonic development and in neonates (PubMed:16118274). Important for normal permeability barrier function of the skin in neonates (PubMed:16118274).|||The histidine box domains are involved in binding the catalytic metal ions.|||Up-regulated by agonists that activate NR1H3 (PubMed:12815040). Slightly down-regulated by a high-carbohydrate diet enriched in unsaturated fatty acids (PubMed:12815040). http://togogenome.org/gene/10090:Sp3 ^@ http://purl.uniprot.org/uniprot/O70494 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by histone acetyltransferase p300, deacetylated by HDACs. Acetylation/deacetylation states regulate transcriptional activity. Acetylation appears to activate transcription. Alternate sumoylation and acetylation at Lys-553 also control transcriptional activity (By similarity).|||Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Interacts with HLTF; the interaction may be required for basal transcriptional activity of HLTF. Interacts with HDAC1; the interaction deacetylates SP3 and regulates its transcriptional activity. Interacts with HDAC2 (preferably the CK2-phosphorylated form); the interaction deacetylates SP3 and regulates its transcriptional activity. Ceramides can also regulate acetylation/deacetylation events through altering the interaction of HDAC with SP3. Interacts with MEIS2 isoform Meis2D and PBX1 isoform PBX1a (By similarity).|||Nucleus|||PML body|||Sumoylated on all isoforms. Sumoylated on 2 sites in longer isoforms with Lys-553 being the major site. Sumoylation at this site promotes nuclear localization to the nuclear periphery, nuclear dots and PML nuclear bodies. Sumoylation on Lys-553 represses the transactivation activity, except for the largest isoform which has little effect on transactivation. Alternate sumoylation and acetylation at Lys-553 also control transcriptional activity (By similarity).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional factor that can act as an activator or repressor depending on isoform and/or post-translational modifications. Binds to GT and GC boxes promoter elements. Competes with SP1 for the GC-box promoters. Weak activator of transcription but can activate a number of genes involved in different processes such as cell-cycle regulation, hormone-induction and house-keeping (By similarity). http://togogenome.org/gene/10090:Tm4sf5 ^@ http://purl.uniprot.org/uniprot/Q91XF2|||http://purl.uniprot.org/uniprot/Q9D8G1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the L6 tetraspanin family.|||Membrane http://togogenome.org/gene/10090:Ms4a2 ^@ http://purl.uniprot.org/uniprot/A0A087WPM9|||http://purl.uniprot.org/uniprot/B2RTF7|||http://purl.uniprot.org/uniprot/P20490|||http://purl.uniprot.org/uniprot/Q3UNT6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MS4A family.|||High affinity receptor that binds to the Fc region of immunoglobulins epsilon. Aggregation of FCER1 by multivalent antigens is required for the full mast cell response, including the release of preformed mediators (such as histamine) by degranulation and de novo production of lipid mediators and cytokines. Also mediates the secretion of important lymphokines. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators responsible for the manifestations of allergy.|||Membrane|||Phosphorylated on tyrosine residues by LYN.|||Tetramer of an alpha chain, a beta chain, and two disulfide linked gamma chains. Binds LILRB1. Interacts with FGR (By similarity). Interacts with FGR and FES/FPS. Interacts with LYN. http://togogenome.org/gene/10090:Ltn1 ^@ http://purl.uniprot.org/uniprot/Q6A009 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Belongs to the LTN1 family.|||Component of the ribosome quality control complex (RQC), composed of at least the E3 ubiquitin ligase LTN1 and NEMF associated with the 60S ribosomal subunit. The complex probably also contains TCF25 as well as VCP/p97 and its ubiquitin-binding cofactors.|||E3 ubiquitin-protein ligase (PubMed:19196968). component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (By similarity). Within the RQC complex, LTN1 is recruited to stalled 60S ribosomal subunits by NEMF and mediates ubiquitination of stalled nascent chains (By similarity). Ubiquitination leads to VCP/p97 recruitment for extraction and degradation of the incomplete translation product (By similarity).|||Embryonic lethality. Mice with a milder mutant caused by an internal in-frame deletion of exon 11, producing a 14-amino acid deletion prior to the RING-type zinc finger, display profound early-onset and progressive neurological and motor dysfunction.|||Was named listerin because of the 'tilting' or 'listing' phenotype observed in mutant mice.|||Widely expressed, including in the brain and spinal cord.|||cytosol http://togogenome.org/gene/10090:Mgll ^@ http://purl.uniprot.org/uniprot/O35678 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Monoacylglycerol lipase family.|||Converts monoacylglycerides to free fatty acids and glycerol (PubMed:9341166, PubMed:17700715, PubMed:18096503, PubMed:19029917, PubMed:20554061, PubMed:20729846, PubMed:21454566). Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (PubMed:9341166, PubMed:17700715, PubMed:18096503, PubMed:19029917, PubMed:20554061, PubMed:20729846, PubMed:21454566). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (By similarity).|||Homodimer.|||Membrane|||Mice display a reduction in monoglyceride hydrolase activity and a concomitant increase in monoglyceride levels in adipose tissue, brain, and liver (PubMed:20554061). Ten-fold increase in brain 2-arachidonoylglycerol levels, combined with low levels of brain arachidonic acid (PubMed:20554061, PubMed:20729846).|||Short-term inhibition causes analgesia, while long-term inhibition causes tolerance to endocannabinoids acting on brain cannabinoid receptor CNR1, and a reduction in brain cannabinoid receptor CNR1 activity.|||Ubiquitous.|||cytosol http://togogenome.org/gene/10090:Sspo ^@ http://purl.uniprot.org/uniprot/E9Q0I4 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thrombospondin family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular space http://togogenome.org/gene/10090:Pim3 ^@ http://purl.uniprot.org/uniprot/P58750|||http://purl.uniprot.org/uniprot/Q3TX64 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.|||By glucose in pancreatic-beta-cells.|||Cytoplasm|||Detected in pancreas but exclusively in beta-cells.|||Interacts with BAD (By similarity). Interacts with PPP2CA; this interaction promotes dephosphorylation of PIM3, ubiquitination and proteasomal degradation (By similarity). Interacts with SOCS6.|||Mice are viable and fertile, with a profound reduction in body size at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size. Deficient mice have also an increased glucose tolerance.|||Phosphorylated. Interaction with PPP2CA promotes dephosphorylation (By similarity).|||Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation.|||Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis and promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression and protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth.|||Ubiquitinated, leading to proteasomal degradation. http://togogenome.org/gene/10090:Tada3 ^@ http://purl.uniprot.org/uniprot/Q8R0L9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NGG1 family.|||Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex. Also known as a coactivator for p53/TP53-dependent transcriptional activation (By similarity). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (By similarity).|||Nucleus|||The PCAF complex is composed of a number of TBP-associated factors (TAFS), such as TAF5, TAF5L, TAF6, TAF6L, TAF9, TAF10 and TAF12, PCAF, and also PCAF-associated factors (PAFs), such as TADA2L/ADA2, TADA3L/ADA3 and SPT3. Interacts directly with TADA2L and PCAF and also with the high-risk HPV oncoprotein E6. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Component of the TFTC-HAT complex (By similarity). Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). http://togogenome.org/gene/10090:Rem2 ^@ http://purl.uniprot.org/uniprot/E9Q4D5|||http://purl.uniprot.org/uniprot/Q8VEL9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. RGK family.|||Binds GTP saturably and exhibits a low intrinsic rate of GTP hydrolysis.|||Cell membrane http://togogenome.org/gene/10090:Msmb ^@ http://purl.uniprot.org/uniprot/O08540 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the beta-microseminoprotein family.|||Homodimer; Interacts with PI16.|||Secreted http://togogenome.org/gene/10090:Tafa5 ^@ http://purl.uniprot.org/uniprot/Q91WE9 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a chemokine-like protein by regulating cell proliferation and migration through activation of G protein-coupled receptors (GPCRs), such as S1PR2 and FPR2 (PubMed:29453251, PubMed:29138422). Stimulates chemotactic migration of macrophages mediated by the MAPK3/ERK1 and AKT1 pathway (PubMed:29138422). Blocks TNFSF11/RANKL-induced osteoclast formation from macrophages by inhibiting up-regulation of osteoclast fusogenic and differentiation genes (PubMed:29138422). Stimulation of macrophage migration and inhibition of osteoclast formation is mediated through the GPCR FPR2 (PubMed:29138422). Acts as an adipokine by negatively regulating vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor stimulation via GPCR S1PR2 and G protein GNA12/GNA13-transmitted RHOA signaling (By similarity). Inhibits injury-induced cell proliferation and neointima formation in the femoral arteries (PubMed:29453251).|||Belongs to the TAFA family.|||Contains a predicted signal peptide at positions 1-25.|||Expressed in the subcutaneous, brown, epididymal and perirenal adipose tissue (at protein level).|||Repressed in epididymal adipose tissue of diet-induced obese mice or leptin receptor-deficient mice.|||Secreted http://togogenome.org/gene/10090:Pik3ca ^@ http://purl.uniprot.org/uniprot/P42337 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the PI3/PI4-kinase family.|||Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:8139567). Interacts with IRS1 in nuclear extracts (PubMed:15197263). Interacts with RUFY3. Interacts with RASD2. Interacts with APPL1 (By similarity). Interacts with HRAS and KRAS (PubMed:17540175). Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (PubMed:17540175). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity).|||Lethal. Embryonic fibroblasts cells are resistant to oncogenic transformation induced by oncogenic receptor tyrosine kinases (RTKs), are unable to differentiate into adipocytes and deficient in cellular signaling in response to various growth factors. Defective responsiveness to insulin led to reduced somatic growth, hyperinsulinemia, glucose intolerance, hyperphagia and increased adiposity.|||Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Also has serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS. Plays a role in the positive regulation of phagocytosis and pinocytosis (PubMed:19604150).|||The PI3K-ABD domain and the PI3K-RBD domain interact with the PI3K/PI4K kinase domain. The C2 PI3K-type domain may facilitate the recruitment to the plasma membrane. The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1, and the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1. http://togogenome.org/gene/10090:Gpr22 ^@ http://purl.uniprot.org/uniprot/G3X9C3|||http://purl.uniprot.org/uniprot/Q8BZL4 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant levels detected in the brain and heart and no detectable expression in other peripheral tissues.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Decreased expression in heart following aortic banding, a procedure that mimics cardiac hypertrophy produced by high blood pressure.|||Membrane|||No visible phenotype, however mice display increased susceptibility to heart failure under conditions of hemodynamic stress.|||Orphan G-protein coupled receptor. Seems to act through a G(i)/G(o) mediated pathway (By similarity). May be involved in ciliogenesis (By similarity). http://togogenome.org/gene/10090:Actr1a ^@ http://purl.uniprot.org/uniprot/P61164 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin family. ARP1 subfamily.|||Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.|||Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The filament contains 8 copies of ACTR1A and 1 ACTB. Interacts with dynein and adapters such as BICD2 (By similarity). Interacts with BCCIP (isoform 2/alpha) (By similarity).|||cell cortex|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:P3h4 ^@ http://purl.uniprot.org/uniprot/Q8K2B0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the leprecan family.|||Detected in calvaria, cartilage, kidney, ribs, and at lower levels in tail (PubMed:23959653, PubMed:27119146). Detected in proliferating and prehypertrophic chondrocytes in the growth plate of long bones and in mineralizing chondro-osseus bone collar and cortical bone (PubMed:23959653). Detected on osteoblasts in long bones (PubMed:23959653, PubMed:27119146). Detected in skin fibroblasts (at protein level) (PubMed:27119146). Detected in fetal ribs, and in tibia and metatarsus from neonates (PubMed:23959653).|||Endoplasmic reticulum|||Interacts with PLOD1, P3H3 and PPIB. Identified in a complex with PLOD1 and P3H3.|||No visible phenotype at birth (PubMed:23959653, PubMed:27119146, PubMed:28115524). Mice are born at the expected Mendelian rate (PubMed:23959653, PubMed:27119146). Two and six month old mutant mice display a decreased ratio between trabecular bone volume and tissue volume in tibia and femur, plus decreased connectivity density in femur and tibia (PubMed:23959653, PubMed:27119146). Osteoblast number is not affected, while osteoclast numbers are increased, suggesting that increased bone resorption is the cause for the low bone mass phenotype (PubMed:23959653). Lysine hydroxylation of skin and bone collagen alpha chains is strongly reduced (PubMed:27119146, PubMed:28115524). In contrast, prolyl 3-hydroxylation is not affected (PubMed:23959653, PubMed:27119146). Dorsal skin displays impaired packing of collagen fibrils, decreased skin tensile strength, decreased skin stiffness and increased skin fragility (PubMed:27119146, PubMed:28115524). Likewise, mice deficient for both P3h3 and P3h4 display decreased lysine hydroxylation of collagen alpha chains, but normal collagen prolyl 3-hydroxylation (PubMed:28115524).|||Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils (PubMed:27119146). Required for normal bone density and normal skin stability via its role in hydroxylation of lysine residues in collagen alpha chains and in collagen fibril assembly (PubMed:23959653, PubMed:27119146, PubMed:28115524). http://togogenome.org/gene/10090:Coa6 ^@ http://purl.uniprot.org/uniprot/Q8BGD8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 6B family.|||Found in a complex with TMEM177, COX20, MT-CO2/COX2, COX18, SCO1 and SCO2. Interacts with COA1, MT-CO2/COX2, SCO1, SCO2 and COX20. Interacts with COX20 in a MT-CO2/COX2- and COX18-dependent manner. Interacts with COX16.|||Involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2. Thereby, may regulate early steps of complex IV assembly. Mitochondrial respiratory chain complex IV or cytochrome c oxidase is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. May also be required for efficient formation of respiratory supercomplexes comprised of complexes III and IV.|||Mitochondrion|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Or10ak12 ^@ http://purl.uniprot.org/uniprot/B2RVY8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cep170 ^@ http://purl.uniprot.org/uniprot/H7BX26|||http://purl.uniprot.org/uniprot/Q6A065 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP170 family.|||Interacts with CCDC68 and CCDC120; leading to recruitment to centrosomes (By similarity). Interacts with PLK1 (By similarity). Interacts with NIN (PubMed:27565344). Interacts with FHDC1 (PubMed:29742020). Interacts with CCDC61 (By similarity). Interacts with TBK1; efficient complex formation may be dependent on the presence of CCDC61 (By similarity).|||Phosphorylated; probably by PLK1.|||Plays a role in microtubule organization. Required for centriole subdistal appendage assembly.|||centriole|||centrosome|||spindle http://togogenome.org/gene/10090:Gdi2 ^@ http://purl.uniprot.org/uniprot/Q3UPA3|||http://purl.uniprot.org/uniprot/Q61598 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Rab GDI family.|||Cytoplasm|||GDP-dissociation inhibitor preventing the GDP to GTP exchange of most Rab proteins. By keeping these small GTPases in their inactive GDP-bound form regulates intracellular membrane trafficking. Negatively regulates protein transport to the cilium and ciliogenesis through the inhibition of RAB8A.|||Interacts with RHOH (By similarity). Interacts with the non-phosphorylated forms of RAB3A, RAB3B, RAB3C, RAB5A, RAB5B, RAB5C, RAB8B, RAB10, RAB12, RAB35, and RAB43; binds RAB3D to a lesser extent (By similarity). Interacts with RAB8A (GDP-bound inactive form); prevents RAB8A activation (PubMed:25860027). Interacts with DZIP1; negatively regulates the interaction of GDI2 with GDP-bound RAB8A (PubMed:25860027).|||Membrane|||Regulates the GDP/GTP exchange reaction of most RAB proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP. http://togogenome.org/gene/10090:Atg16l2 ^@ http://purl.uniprot.org/uniprot/Q6KAU8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATG16L2-deficient mice are viable and born at Mendelian proportions. Deficient mice exhibit intact canonical autophagy.|||Although ATG16L2 is structurally similar to ATG16L1 and is likewise able to form a complex with the autophagy proteins ATG5 and ATG12, overexpression and knockdown studies suggest that ATG16L2 is not essential for canonical autophagy.|||Belongs to the WD repeat ATG16 family.|||Homooligomer (PubMed:22082872). Heterooligomer with ATG16L2 (PubMed:22082872). Interacts with ATG5 (PubMed:22082872). Self-oligomerizes to form a 800-kDa complex composed of ATG12-ATG5 and ATG16L2 (PubMed:22082872). Interacts with RAB33B (PubMed:22082872).|||May play a role in regulating epithelial homeostasis in an ATG16L1-dependent manner.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Lypla2 ^@ http://purl.uniprot.org/uniprot/Q9WTL7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins, GAP43, ZDHHC6 or HRAS (By similarity). Deacylates GAP43 (By similarity). Mediates depalmitoylation of ZDHHC6 (By similarity). Has lysophospholipase activity (PubMed:10064901). Hydrolyzes prostaglandin glycerol esters (PG-Gs) (PubMed:25301951). Hydrolyzes PG-Gs in the following order prostaglandin D2-glycerol ester (PGD2-G) > prostaglandin E2 glycerol ester (PGE2-G) > prostaglandin F2-alpha-glycerol ester (PGF2-alpha-G) (By similarity). Hydrolyzes 1-arachidonoylglycerol but not 2-arachidonoylglycerol or arachidonoylethanolamide (By similarity).|||Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.|||Cytoplasm|||Ubiquitous; detected at low levels. http://togogenome.org/gene/10090:Pecam1 ^@ http://purl.uniprot.org/uniprot/Q08481 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (By similarity). Tyr-679 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes (By similarity). Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions (By similarity). Heterophilic interaction with CD177 plays a role in transendothelial migration of neutrophils (By similarity). Homophilic ligation of PECAM1 prevents macrophage-mediated phagocytosis of neighboring viable leukocytes by transmitting a detachment signal (By similarity). Promotes macrophage-mediated phagocytosis of apoptotic leukocytes by tethering them to the phagocytic cells; PECAM1-mediated detachment signal appears to be disabled in apoptotic leukocytes (By similarity). Modulates bradykinin receptor BDKRB2 activation (By similarity). Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in endothelial cells (By similarity). Induces susceptibility to atherosclerosis (PubMed:19048083).|||Cell junction|||Cell membrane|||Isoform 1 and isoform 3 are expressed in lung and platelets.|||Membrane raft|||Mice show reduced atherosclerotic lesions. There is down-regulation of ICAM-1 in endothelial cells at the lesion periphery, and reduced disruption of Cx43 junctional staining at arterial branch points and in the descending aorta.|||Palmitoylation by ZDHHC21 is necessary for cell surface expression in endothelial cells and enrichment in membrane rafts.|||Phosphorylated on Ser and Tyr residues by src kinases after cellular activation (PubMed:16731527). Upon activation, phosphorylated on Ser-718 which probably initiates the dissociation of the membrane-interaction segment (residues 698-718) from the cell membrane allowing the sequential phosphorylation of Tyr-702 and Tyr-679 (By similarity). Constitutively phosphorylated on Ser-723 in resting platelets (By similarity). Phosphorylated on tyrosine residues by FER and FES in response to FCER1 activation (PubMed:16731527). In endothelial cells Fyn mediates mechanical-force (stretch or pull) induced tyrosine phosphorylation (By similarity).|||The Ig-like C2-type domains 2 and 3 contribute to formation of the complex with BDKRB2 and in regulation of its activity.|||Trans-homodimer (via Ig-like C2-type 1 and Ig-like C2-type 2 domains); trans-homodimerization is required for cell-cell interaction. Forms a complex with BDKRB2 and GNAQ. Interacts with BDKRB2 and GNAQ. Interacts with PTPN11; Tyr-702 is critical for PTPN11 recruitment. Interacts with FER. Interacts with CD177; the interaction is Ca(2+)-dependent; the interaction is direct. http://togogenome.org/gene/10090:Lca5 ^@ http://purl.uniprot.org/uniprot/G5E886|||http://purl.uniprot.org/uniprot/G5E887|||http://purl.uniprot.org/uniprot/Q80ST9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Almost ubiquitous, low-level staining at 12.5 dpc. At later stages (14.5 dpc, 16.5 dpc and 18.5 dpc), staining of the eye, inner ear, kidney, regions of the central and peripheral neural system, the gut and the ciliated epithelium of the nasopharynx, trachea and lungs is more pronounced. Expression in the mouse eye shifted during development from the ganglion cell layer to the photoreceptors. In adult eyes (P90), expression is limited to the photoreceptor cell layer.|||Belongs to the LCA5 family.|||Deficient mice exhibit retinal patches of depigmentation, lack rod and cone ERG responses to light stimuli, and show loss of ciliary intraflagellar transport function in photoreceptors leading to failure of outer segment formation and photoreceptor degeneration.|||Detected in several tissues.|||Interacts with NINL. Interacts with OFD1. Interacts with FAM161A. Interacts with components of the IFT complex B.|||Involved in intraflagellar protein (IFT) transport in photoreceptor cilia.|||cilium|||cilium axoneme|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Zdhhc21 ^@ http://purl.uniprot.org/uniprot/Q9D270 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family.|||Cell membrane|||Defects in zdhhc21 are the cause of the depilated (dep) phenotype. It is a recessive phenotype characterized by variable hair loss, with thinner and shorter hairs remaining in a greasy coat which is due to a defect in the epidermis, rather than the dermis (PubMed:19956733). Depilated (dep) mutant mice are protected against endothelial dysfunction in systemic inflammatory response syndrome (PubMed:27653213). They are also tachycardic and hypotensive (PubMed:26715683).|||Golgi apparatus membrane|||In the developing skin, expression is not be detected prior to hair follicle induction (13 dpc). Expression is initially detected in the inner root sheath (IRS) of developing vibrissae follicles at 16 dpc and later in the developing IRS of 18.5 dpc pelage follicles.|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates (PubMed:19956733, PubMed:26715683, PubMed:27653213). Palmitoylates sex steroid hormone receptors, including ESR1, PGR and AR, thereby regulating their targeting to the plasma membrane. This affects rapid intracellular signaling by sex hormones via ERK and AKT kinases and the generation of cAMP, but does not affect that mediated by their nuclear receptor (By similarity). Palmitoylates FYN, regulates its localization in hair follicles and plays a key role in epidermal homeostasis and hair follicle differentiation (PubMed:19956733). Through the palmitoylation of PLCB1 and the regulation of PLCB1 downstream signaling may indirectly regulate the function of the endothelial barrier and the adhesion of leukocytes to the endothelium (PubMed:27653213). Has also a palmitoyltransferase activity toward ADRA1D, positively regulating its activity and expression and may thereby play a role in vascular contraction (PubMed:26715683). May also palmitoylate eNOS and LCK (PubMed:19956733).|||The DHHC domain is required for palmitoyltransferase activity.|||Widely expressed (PubMed:26715683). Expressed in Henle's layer within the hair bulb and the hair shaft cuticle (at protein level) (PubMed:19956733). Expression is limited to the post-mitotic lineages of inner root sheath (IRS) and cuticle (PubMed:19956733).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Defb40 ^@ http://purl.uniprot.org/uniprot/Q70KL2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Only expressed in epididymis (corpus, cauda and caput).|||Secreted http://togogenome.org/gene/10090:Cd226 ^@ http://purl.uniprot.org/uniprot/Q8K4F0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with PVR and NECTIN2. Competes with PVRIG for NECTIN2-binding.|||Involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell. Cell surface receptor for NECTIN2. Upon ligand binding, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Competes with PVRIG for NECTIN2-binding.|||Phosphorylated. http://togogenome.org/gene/10090:Fzd9 ^@ http://purl.uniprot.org/uniprot/Q9R216 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Has been first described as FZD3 in literature.|||Homozygous Fzd9 knockout mice show deficits in spatial memory behaviors. Heterozygous and homozygous Fzd9 knockout mice appear healthy, develop normally, and are fertile (PubMed:15930120). Homozygous Fzd9 knockout mice display osteopenia (PubMed:21402791).|||In the embryo, found in the neural tube, trunk skeletal muscle precursors (myotomes), limb skeletal anlagen, craniofacial regions and nephric ducts. In the adult, expression is abundant in heart, brain, testis and skeletal muscle. In the testis, expressed in all spermatogenic cell types. Lower levels in adult lung, liver and kidney. Barely detectable in spleen. Expressed also in chondrocytes.|||Increases during the initial stages of osteoblast differentiation.|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Not detected at 7 dpc, weakly at 11 dpc and strongly at 15 dpc and 17 dpc. Expression covers the entire neural tube at 9.5 dpc, decreases at 10.5 dpc and becomes detectable only in the lumbar to tail regions at 11.5 dpc. In the somites, expression begins at 10.5 dpc to become up-regulated all along the rostrocaudal trunk axis at 11.5 dpc. In craniofacial territories, expression is first detected at 11.5 dpc in restricted areas of the nose, the maxillar mandibular and second branchial arch anlagen. At 11.5 dpc, predominantly expressed in restricted areas of the nose, dorsally to the eye and in the caudal pharyngeal region. Highly expressed at early stages of neuromuscular junction assembly (14.5 dpc) and gradually decreases as development proceeds, being more than about 4-fold less expressed in 19.5 dpc.|||Receptor for WNT2 that is coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (By similarity). Plays a role in neuromuscular junction (NMJ) assembly by negatively regulating the clustering of acetylcholine receptors (AChR) through the beta-catenin canonical signaling pathway (PubMed:24860427). May play a role in neural progenitor cells (NPCs) viability through the beta-catenin canonical signaling pathway by negatively regulating cell cycle arrest leading to inhibition of neuron apoptotic process (By similarity). During hippocampal development, regulates neuroblast proliferation and apoptotic cell death (PubMed:15930120). Controls bone formation through non canonical Wnt signaling mediated via ISG15 (PubMed:21402791). Positively regulates bone regeneration through non canonical Wnt signaling (PubMed:24391920).|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:1700021F07Rik ^@ http://purl.uniprot.org/uniprot/Q9DA42 ^@ Subcellular Location Annotation ^@ cilium http://togogenome.org/gene/10090:Dmbt1 ^@ http://purl.uniprot.org/uniprot/A0A140LI59|||http://purl.uniprot.org/uniprot/E9QPG8|||http://purl.uniprot.org/uniprot/Q60997 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DMBT1 family.|||Highly N- and O-glycosylated. The O-glycans are heavily sulfated. O-glycosylation and sulfation in pancreatic acinar cells are required for zymogen granule maturation. Glycoconjugate composition changes during development with fucose only acquired post-natally during weaning.|||Interacts with LGALS3. Binds SPAR in a calcium-dependent manner (By similarity). Binds SFTPD in a calcium-dependent manner.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play roles in mucosal defense system and cellular immune defense. May play a role in liver regeneration. May be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. May function as a binding protein in saliva for the regulation of taste sensation. May play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract (By similarity). Required for terminal differentiation of columnar epithelial cells during early embryogenesis. Displays a broad calcium-dependent binding spectrum against both Gram-positive and Gram-negative bacteria, suggesting a role in defense against bacterial pathogens. Binds to a range of poly-sulfated and poly-phosphorylated ligands which may explain its broad bacterial-binding specificity. Inhibits cytoinvasion of S.enterica. Associates with the actin cytoskeleton and is involved in its remodeling during regulated exocytosis. Interacts with pancreatic zymogens in a pH-dependent manner and may act as a Golgi cargo receptor in the regulated secretory pathway of the pancreatic acinar cell.|||Present in the 3.5 dpc blastocyst. Levels increase to a maximum between 18.5 dpc and birth and decrease gradually between birth and adulthood with the greatest decreases occurring between neonate and P1 and between P9 and P16 (at protein level). Expressed in the primitive endoderm at 4.5 dpc. At 9.5 dpc, expressed in midbrain, notochord, liver primordium, midgut and hindgut.|||Secreted|||Strongly expressed in acini and duct epithelial cells of the exocrine pancreas but not in the islets of Langerhans. Expressed in gall bladder, salivary glands and in the epithelium lining larger hepatic ducts, but not in the liver parenchyma, stomach or lung. Expressed along the intestinal tract including duodenum, jejunum, ileum and colon (at protein level). Expressed in glands associated with vomeronasal tissues. Expressed in the vomeronasal gland and posterior gland of nasal septum. Weakly expressed in lateral nasal gland. CFTR knockout mice show increased expression in pancreas, duodenum and small intestine but not in gall bladder. In pancreas and small intestine, increased expression occurs after the appearance of dilated lumina.|||The SRCR domains mediate binding to bacteria.|||Variable phenotypes have been reported. In some studies mice display normal development and viability with impaired exocrine pancreatic function and no development of gastrointestinal tumors (PubMed:17983803, PubMed:18202109). In other studies mice die between 4.5 dpc and 5.5 dpc due to defects in the differentiation of the primitive endoderm layer (PubMed:15452149).|||secretory vesicle membrane http://togogenome.org/gene/10090:Ugt1a5 ^@ http://purl.uniprot.org/uniprot/B2RT14|||http://purl.uniprot.org/uniprot/Q6XL48 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Pianp ^@ http://purl.uniprot.org/uniprot/Q6P1B3 ^@ Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a ligand for PILRA in neuronal tissues, where it may be involved in immune regulation.|||Chimeric cDNA.|||Mainly expressed in brain and spinal cord. Weak expression also detected in heart, kidney, spleen and lymph node. Virtually no expression detected in liver and embryo relative to brain.|||Membrane|||O-glycosylation at Thr-136 is essential for recognition by PILRA. http://togogenome.org/gene/10090:Pcbp2 ^@ http://purl.uniprot.org/uniprot/Q61990 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Embryos undergo normal development until midgestation (12.5 to 13.5 dpc), at which time they undergo a dramatic loss in viability associated with combined cardiovascular and hematopoietic abnormalities (PubMed:26527618). Conditional deletion in the erythroid lineage is not lethal and does not lead to defects in the hematopoietic pathway (PubMed:34180713). Mice lacking Pcbp1 and Pcbp2 in the erythroid lineage die at midgestation; lethality is caused by impaired erythroid development and loss of blood formation (PubMed:34180713).|||Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with IFIH1 and RNF135. Interacts with MAVS (via C-terminus) and ITCH (via WW domains). Interacts with CGAS; preventing the formation of liquid-like droplets in which CGAS is activated.|||Nucleus|||Phosphorylated. The non-phosphorylated form(s) exhibited the strongest poly(rC)-binding activity.|||Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:8367306, PubMed:8208614). Major cellular poly(rC)-binding protein (By similarity). Binds also poly(rU) (By similarity). Acts as a negative regulator of antiviral signaling (By similarity). Negatively regulates cellular antiviral responses mediated by MAVS signaling (By similarity). It acts as an adapter between MAVS and the E3 ubiquitin ligase ITCH, therefore triggering MAVS ubiquitination and degradation (By similarity). Negativeley regulates the cGAS-STING pathway via interaction with CGAS, preventing the formation of liquid-like droplets in which CGAS is activated (By similarity). Together with PCBP1, required for erythropoiesis, possibly by regulating mRNA splicing (PubMed:34180713).|||The KH domains mediates poly(C) binding. http://togogenome.org/gene/10090:Ptbp3 ^@ http://purl.uniprot.org/uniprot/Q8BHD7 ^@ Function|||Subunit ^@ Interacts with THBS4 (via the acidic amphipathic C-terminus).|||RNA-binding protein that mediates pre-mRNA alternative splicing regulation. Plays a role in the regulation of cell proliferation, differentiation and migration. Positive regulator of EPO-dependent erythropoiesis. Participates in cell differentiation regulation by repressing tissue-specific exons. Promotes Fas exon 6 skipping. Binds RNA, preferentially to both poly(G) and poly(U) (By similarity). http://togogenome.org/gene/10090:Clstn2 ^@ http://purl.uniprot.org/uniprot/Q9ER65 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calsyntenin family.|||Binds synaptic Ca(2+) with its cytoplasmic domain.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Mice show a deficit of GABAergic interneurons, associated with hyperactivity, deficient spatial memory and social behavior (PubMed:26171716, PubMed:28647593). Mice show a selective reduction in functional inhibitory synapses, associated with a selective reduction of parvalbumin interneurons in hippocampus and cortex (PubMed:26171716). In neurons, a reduction of symmetric (inhibitory) synaptic density, length of synaptic contacts and postsynaptic density is observed (PubMed:31529526). Moreover, cortical neurons are characterized by the predominance of the simplified type of synapses with the emergence of negative curvature of the synaptic zone (PubMed:31529526). Presynaptic zones of cortical neurons show an increased number of synaptic vesicles in opposite to the decreased number of synaptic vesicles in the presynaptic zones of hippocampal neurons (PubMed:31529526). Mice lacking Clstn1, Clstn2 and Clstn3 display behavior disorders, characterized by hyperactivity in normal environment, hypersensitivity to stress, and show tendency to freeze in novel environments (PubMed:35279170).|||Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate synapse formation, and which is involved in learning and memory (PubMed:24613359, PubMed:26171716, PubMed:31529526). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with neurexin-alpha at the presynaptic membrane (By similarity).|||Postsynaptic cell membrane|||Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by gamma-secretase within the transmembrane domain releases the beta-Alc-gamma chain in the extracellular milieu and produces an intracellular fragment (AlcICD). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with PSEN1.|||Restricted to the brain (PubMed:12498782). In the cerebral cortex, found in the somas and neuropil of all layers (PubMed:12498782). Expressed at highest levels in neurons of cortical layers 5 and 6 and, at lower levels, in neurons of the upper layers (PubMed:12498782). Highly expressed in Purkinje cells (PubMed:12498782). Also found in a few scattered interneurons throughout the granule cell layer and occasionally in neurons in the molecular layer (at protein level) (PubMed:12498782). Present throughout all cortical layers, highest levels in GABAergic neurons (based on morphology and distribution pattern) (PubMed:12498782).|||dendrite http://togogenome.org/gene/10090:Lrrc19 ^@ http://purl.uniprot.org/uniprot/Q8BZT5 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by TLR ligands such as LPS, bacterial DNA and peptidoglycan.|||Interacts with TRAF2 and TRAF6.|||Knockout mice display increased longevity compared with the cohoused wild-type littermates. Almost all mutant mice remain alive, whereas most of the wild-type mice (>80%) di after 2 years on standard chow. Mutant body weights are lower than those of wild-type. Gut tissues of wild-type mice show slight inflammation whereas mutant mouse gut tissues do not. The gut tissues of mutant mice are more yellow and the colon tissues are thinner in mutant mice than in WT mice and the ceca are enlarged significantly (PubMed:26776522). They show lower expression of cytokines such as TNF, ILB, IL6, IFNG, IL17 and IL12 in the gut tissues (PubMed:26776522). Mice are resistant to dextran sodium sulfate (DSS)-induced colitis and colon cancer (PubMed:26776522). They have fewer and smaller gut tissue-associated lymph node Peyer plaques compared with cohoused wild-type mice with fewer adaptive immune cells that have accumulated in their gut immune systems (PubMed:26776522). Mutants show reduced expression of several chemokines, including CCL6, CCL9, CXCL9, and CXCL10 (PubMed:26776522). They also show an altered gut microbiota and reduced expression of REGs (PubMed:26776522). Mutants are more susceptible to uropathogenic Escherichia coli infections (PubMed:25026888).|||Membrane|||Pathogen-recognition receptor which mediates the activation of TRAF2- and TRAF6 NF-kappa-B signaling pathways and induces the expression of pro-inflammatory cytokines (PubMed:26776522, PubMed:19679103, PubMed:25026888). In kidney, prevents infection by uropathogenic bacteria by inducing the production of cytokines, chemokines and antimicrobial substances (PubMed:25026888). In gut, involved in host-microbiota interactions, plays a critical role in promoting the recruitment of immune cells and intestinal inflammation (PubMed:26776522).|||Strongly expressed in kidney, also expressed in spleen, intestine and colon (PubMed:26776522, PubMed:19679103). Highly expressed in epithelial cells (PubMed:26776522). In kidney, mainly expressed in renal collecting duct epithelial cells (PubMed:25026888). http://togogenome.org/gene/10090:Mars2 ^@ http://purl.uniprot.org/uniprot/A2RT28|||http://purl.uniprot.org/uniprot/Q499X9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Mitochondrion matrix http://togogenome.org/gene/10090:Ovol2 ^@ http://purl.uniprot.org/uniprot/Q3TIV4|||http://purl.uniprot.org/uniprot/Q8CIV7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Down-regulated during embryonic stem cell neural differentiation and up-regulated by BMP4.|||Expressed during early-mid embryogenesis, particularly in the inner cell mass at 3.5 dpc, in epiblast at 6.5 dpc, and at later stages in ectodermally derived tissues such as the rostral surface ectoderm (PubMed:16423343). Expressed in embryonic stem cells, epiblasts of 6.4 dpc embryos and primordial germ cells (PGCs) (PubMed:28059165). High expression levels in PGCs of 8.5 dpc embryos decrease over embryogenesis (PubMed:28059165). Up-regulated during prepupertal testis development (PubMed:15225875).|||Expressed highly in testis, specifically in spermatocytes. Expressed also in skin and at lower levels in the ovary (PubMed:12213202, PubMed:15225875, PubMed:9468311, PubMed:36228616). Expressed in adipose tissues. Expression is lower than in testis and a relatively higher expression level is detected in the stromal vascular fraction (SVF) than in fat cells themselves (PubMed:36228616).|||Interacts (via zinc-finger domains) with CEBPA (via bZIP domain); the interaction inhibits the transcription factor activity of CEBPA and is required to repress adipogenesis.|||Major form in the testis.|||Mutant embryos are small and die at 9.5 dpc-10.5 dpc with an open neural tube, impaired extra-embryonic and embryonic vascularization, abnormal cardiogenesis and placental defects (PubMed:16423343). Reduced number of primordial germ cells in 8.0 dpc embryos (PubMed:28059165).|||Nucleus|||Zinc-finger transcription repressor factor (PubMed:15225875, PubMed:23319585, PubMed:36228616). Plays a critical role in maintaining the identity of epithelial lineages by suppressing epithelial-to mesenchymal transition (EMT) mainly through the repression of ZEB1, an EMT inducer (PubMed:24735878, PubMed:24735879). Positively regulates neuronal differentiation (PubMed:16423343, PubMed:23319585). Suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing MYC and NOTCH1 (By similarity). Important for the correct development of primordial germ cells in embryos (PubMed:28059165). Plays dual functions in thermogenesis and adipogenesis to maintain energy balance. Essential for brown/beige adipose tissue-mediated thermogenesis, is necessary for the development of brown adipocytes. In white adipose tissues, limits adipogenesis by blocking CEBPA binding to its transcriptional targets and inhibiting its transcription factor activity (PubMed:36228616). http://togogenome.org/gene/10090:A430005L14Rik ^@ http://purl.uniprot.org/uniprot/E9PUH0|||http://purl.uniprot.org/uniprot/Q80WR5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UPF0688 family.|||Nucleus http://togogenome.org/gene/10090:Fam124b ^@ http://purl.uniprot.org/uniprot/Q8BLQ0 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At embryonic stage 12.5 dpc, detected in a wide range of tissues including brain, heart, lung, cochlea, dorsal root ganglia, and liver (at protein level).|||Belongs to the FAM124 family.|||Expressed strongly in lung, at slightly lower levels in heart, kidney, brain and testis, and weakly in liver (at protein level). In brain, highly expressed in cortex, hippocampus, dentate gyrus, caudate putamen and cerebellum (at protein level).|||Interacts with CHD7 and CHD8.|||Nucleus http://togogenome.org/gene/10090:Rad51 ^@ http://purl.uniprot.org/uniprot/Q08297 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RecA family. RAD51 subfamily.|||Chromosome|||Cytoplasm|||Expressed in the testes (at protein level) (PubMed:35547804, PubMed:8341671). Expressed in the brain (at protein level) (PubMed:22305526). Expressed in the thymus, spleen, ovary and small intestine (PubMed:8341671).|||Expression in the brain is strongest at day 12 dpc, particularly in the cortical ventricular zone. In the cortex of newborn mice (P0), RAD51 is mainly present in the subplate and, in lesser amounts, in layer V. It is detected in a subpopulation of corticospinal axons at the pyramidal decussation in 2-day-old (P2) mice.|||Forms linear homooligomers, giving rise to a RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. Interacts with BRCA1 and either directly or indirectly with p53. Interacts with XRCC3, RAD54L and RAD54B. Interacts with the BCDX2 subcomplex RAD51C:RAD51B. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (By similarity). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with RAD51AP1 and RAD51AP2. Interacts with CHEK1, and this may require prior phosphorylation of CHEK1 (By similarity). Interacts with the MND1-PSMC3IP heterodimer (PubMed:15834424). Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with SPIDR; the interaction is direct and recruits RAD51 to DNA damage sites. Interacts with FIGNL1 (via N-terminal one-half region); the interaction is direct. Interacts with RAD51AP1 (via C-terminal region); the interaction is direct (By similarity). Interacts with NABP2, RPA1, PALB2 and RAD51. Interacts with SWI5/C9orf119, and at lower level with SFR1/MEIR5 (PubMed:20976249). Interacts with hyperphosphorylated RPA2; this interaction is necessary for efficient recruitment to chromatin in response to DNA damage. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with PARPBP, BRCA2 and RECQL5; these interactions interfere with the formation of the RAD51-DNA homologous recombination structure. Interacts with POLQ; POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends. Interacts with POLN (By similarity). Interacts with FBH1 (PubMed:24108124). Interacts with RFWD3 (By similarity). Interacts with the MCM8-MCM9 complex; the interaction recruits RAD51 to DNA damage sites (By similarity). Component of a multiprotein complex with MEIOB and SPATA22. Interacts with the complex BRME1:HSF2BP:BRCA2 (PubMed:32345962, PubMed:30760716). Interacts with HELQ; stimulating HELQ DNA helicase activity and ability to unwing DNA (By similarity). Interacts with MMS22L; the interaction is direct and promotes recruitment of RAD51 to sites of DNA damage (By similarity). Interacts with the ATAD5 RFC-like complex (By similarity). Within the ATAD5 RFC-like complex, interacts with ATAD5 (via N-terminus); the interaction is direct and enhanced under replication stress (By similarity). Interacts with WDR48; the interaction is enhanced under replication stress (By similarity).|||Mitochondrion matrix|||Nucleus|||Phosphorylated. Phosphorylation of Thr-309 by CHEK1 may enhance association with chromatin at sites of DNA damage and promote DNA repair by homologous recombination. Phosphorylation by ABL1 inhibits function.|||Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR) (PubMed:15834424). Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Recruited to resolve stalled replication forks during replication stress. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3. Also involved in interstrand cross-link repair (By similarity).|||The nucleus of a mouse embryonic stem (ES) cells contains on average 4.7 x 10(5) molecules.|||Ubiquitinated by the SCF(FBH1) E3 ubiquitin ligase complex, regulating RAD51 subcellular location and preventing its association with DNA. Ubiquitinated by RFWD3 in response to DNA damage: ubiquitination leads to degradation by the proteasome, promoting homologous recombination.|||centrosome|||perinuclear region http://togogenome.org/gene/10090:Zswim7 ^@ http://purl.uniprot.org/uniprot/Q9CWQ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SWS1 family.|||Interacts with RAD51D and XRCC3; involved in homologous recombination repair. Interacts with SWSAP1; they form a functional complex involved in homologous recombination repair and stabilize each other (By similarity).|||Involved in early stages of the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents (By similarity). Required for meiotic progression, hence for fertility (PubMed:33713115).|||Nucleus http://togogenome.org/gene/10090:Ism2 ^@ http://purl.uniprot.org/uniprot/D3Z6A3 ^@ Similarity ^@ Belongs to the isthmin family. http://togogenome.org/gene/10090:Laptm4b ^@ http://purl.uniprot.org/uniprot/B2CZK6|||http://purl.uniprot.org/uniprot/Q91XQ6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LAPTM4/LAPTM5 transporter family.|||Cell membrane|||Cell projection|||Endomembrane system|||Endosome membrane|||Homooligomer; upon reaching the lysosomes. Interacts with MCOLN1. Interacts with NEDD4; may play a role in the lysosomal sorting of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of EGFR degradation. Interacts with PIP5K1C; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C. Interacts with HGS; promotes HGS ubiquitination. Interacts with SNX5. Interacts with SLC3A2 and SLC7A5; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation. Interacts with LRRC32; decreases TGFB1 production in regulatory T cells. Interacts with BECN1; competes with EGFR for LAPTM4B binding; regulates EGFR activity. Interacts with EGFR; positively correlates with EGFR activation.|||Late endosome membrane|||Lysosome membrane|||Required for optimal lysosomal function. Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation. Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation. Plays a role as negative regulator of TGFB1 production in regulatory T cells. Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways.|||Ubiquitinated by NEDD4.|||Undergoes proteolytic cleavage following delivery to the lysosomes.|||multivesicular body lumen|||multivesicular body membrane http://togogenome.org/gene/10090:Ankrd37 ^@ http://purl.uniprot.org/uniprot/Q569N2 ^@ PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed testis, ovary, uterus, kidney, liver, but not in other tissues.|||Nucleus|||Ubiquitinated by the CRL2(FEM1B) complex, leading to its degradation. http://togogenome.org/gene/10090:Eppin ^@ http://purl.uniprot.org/uniprot/Q9DA01 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Androgen dependent. Down-regulated in Sertoli cell-selective androgen receptor knockout mice.|||Cell surface|||Expressed in differentiated spermatogonia in testis. Expressed in spermatogonia cell lines GC-1 spg and GC-2spd(ts) as well as in the Leydig tumor cell line MLTC-1 (at protein level). Expressed specifically in epididymis and testis. Expressed predominantly on the postacrosomal region of mouse spermatozoa, in Sertoli cells, Leydig cells, and round spermatids in the testis, and in the principal cells of the cauda epididymidis epithelium.|||Monomer. Homodimer. Homomultimers. Interacts (via C-terminus) with SEMG1 (via 164-283 AA). Interacts with LTF. Found in a complex with LTF, CLU, EPPIN and SEMG1.|||Secreted|||Serine protease inhibitor that plays an essential role in male reproduction and fertility. Modulates the hydrolysis of SEMG1 by KLK3/PSA (a serine protease), provides antimicrobial protection for spermatozoa in the ejaculate coagulum, and binds SEMG1 thereby inhibiting sperm motility (By similarity). http://togogenome.org/gene/10090:Phldb1 ^@ http://purl.uniprot.org/uniprot/Q6PDH0 ^@ Domain ^@ The PH domain mediates the binding to phosphoinositides. http://togogenome.org/gene/10090:Adgrg2 ^@ http://purl.uniprot.org/uniprot/Q14AX7|||http://purl.uniprot.org/uniprot/Q14BH6|||http://purl.uniprot.org/uniprot/Q8CJ12 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Epididymis-specific expression (at protein level). Associated with apical membranes of efferent ductule and proximal epididymal duct epithelia. Mainly expressed in the nonciliated principal cells of the proximal excurrent ducts.|||Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked.|||Highly glycosylated.|||Membrane|||Mutant male are infertile. Targeted disruption leads to sperm stasis and duct obstruction, resulting from dysregulation of fluid reabsorption.|||Orphan receptor. Could be involved in a signal transduction pathway controlling epididymal function and male fertility. May regulate fluid exchange within epididymis.|||Proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit. http://togogenome.org/gene/10090:Plscr2 ^@ http://purl.uniprot.org/uniprot/Q9DCW2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipid scramblase family.|||Expressed in erythrocyte membranes, blood platelets, blood leukocytes, T- and B-lymphocytes, vascular endothelium, spleen, thymus, prostate, testis, uterus, intestine and colon.|||May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system.|||Membrane|||The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity. http://togogenome.org/gene/10090:Scn10a ^@ http://purl.uniprot.org/uniprot/K3W4P8|||http://purl.uniprot.org/uniprot/Q6QIY3 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.8/SCN10A subfamily.|||Cell membrane|||Expressed in dorsal root ganglion and trigeminal ganglion.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lacks the cysteine which covalently binds the conotoxin GVIIJ. This cysteine (position 815) is speculated in other sodium channel subunits alpha to be implied in covalent binding with the sodium channel subunit beta-2 or beta-4.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Membrane|||Mus musculus is sensitive to the pain-inducing components of the bark scorpion (Centruroides sculpturatus) venom while Onychomys torridus is not. Gln-861 may account for the difference between both rodents and its replacement by a glutamate, the corresponding amino acid found in the Onychomys torridus ortholog, allows inhibition of Snc10a by the venom, which in turn, inhibits sodium currents, blocks action potential propagation and may induce analgesia (PubMed:24159039).|||Phosphorylation at Ser-1452 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.|||Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.|||The channel consists of an ion conducting pore forming alpha-subunit regulated by one or more associated auxiliary subunits SCN1B, SCN2B and SCN3B; electrophysiological properties may vary depending on the type of the associated beta subunits. Found in a number of complexes with PRX, DYNLT1 and PDZD2. Interacts with proteins such as FSTL1, PRX, DYNLT1, PDZD2, S100A10 and many others (By similarity). Interacts with NEDD4 and NEDD4L.|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.|||Ubiquitinated by NEDD4L; which promotes its endocytosis. http://togogenome.org/gene/10090:1810010H24Rik ^@ http://purl.uniprot.org/uniprot/Q08AU9 ^@ Similarity ^@ Belongs to the UPF0450 family. http://togogenome.org/gene/10090:Polr3f ^@ http://purl.uniprot.org/uniprot/Q8C108|||http://purl.uniprot.org/uniprot/Q921X6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPC34/RPC39 RNA polymerase subunit family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. RPC3/POLR3C, RPC6/POLR3F and RPC7/POLR3G form a Pol III subcomplex (By similarity). Directly interacts with POLR3C (By similarity). Interacts with TBP and TFIIIB90 and GTF3C4 (By similarity). Interacts with MAF1 (By similarity). As part of the RNA polymerase III (Pol III) complex, interacts with PKP2 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. May direct RNA Pol III binding to the TFIIIB-DNA complex. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved detecting AT-rich DNA, in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity). Preferentially binds double-stranded DNA (dsDNA) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Myo1a ^@ http://purl.uniprot.org/uniprot/O88329 ^@ Caution|||Function|||PTM|||Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Involved in directing the movement of organelles along actin filaments.|||Phosphorylated by ALPK1.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1). http://togogenome.org/gene/10090:Rtn4rl1 ^@ http://purl.uniprot.org/uniprot/Q8K0S5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 13.5 dpc, strongly expressed in PNS ganglia and developing heart, and weakly expressed in brain and spinal cord. By postnatal day 1, strongly expressed in dorsal root ganglia and in dorsal and gray matter areas of spinal cord. Expressed in various adult brain structures including the amygdala, caudate putamen, cerebellum, cerebral cortex, hippocampus, olfactory bulb and thalamus.|||Belongs to the Nogo receptor family.|||Cell membrane|||Cell projection|||Cell surface receptor that plays a functionally redundant role in postnatal brain development and in regulating axon regeneration in the adult central nervous system (PubMed:22406547, PubMed:27339102). Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG (PubMed:26335717). Plays a role in inhibiting neurite outgrowth and axon regeneration via its binding to neuronal chondroitin sulfate proteoglycans (PubMed:22406547). Binds heparin (PubMed:22406547). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200).|||Detected in brain (at protein level) (PubMed:22406547). Detected in retina ganglion cell layer and inner nuclear layer (PubMed:22406547).|||Identified in a complex that contains RTN4R, RTN4RL1 and NGFR; the interaction depends on the presence of chondroitin sulfate proteoglycans (PubMed:22406547). Does not interact with MAG, OMG and RTN4 (PubMed:12839991).|||Membrane raft|||No visible phenotype (PubMed:22406547). Mice are born at the expected Mendelian rate, are viable and fertile (PubMed:22406547). Compared to wild-type littermates, cultured hippocampus neurons from mutant mice display an increased number of excitatory synapses (PubMed:22325200). Likewise, mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have no visible phenotype, are healthy and viable (PubMed:22406547, PubMed:22325200). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have normal brain size and grossly normal brain anatomy, but display defects of medial brain structures, including an absence of the fasciola cinereum, corpus callosum agenesis and formation of bilateral Probst bundles indicative of the failure of callosally projecting neurons to extend across the midline (PubMed:27339102). Mice with a triple gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 display impaired ability to stay on a rotarod and increased spontaneous locomotion (PubMed:27339102). These mice display an increased number of excitatory synapses in the apical dendritic regions of hippocampus neurons, an increase in the complexity of dendrite structure and increased total dendrite length (PubMed:22325200). One month after birth, mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a significant reduction in the survival of motoneurons (PubMed:26335717). Compared to wild-type or single mutants, cerebellar granule cells from mice lacking Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated inhibition of neurite outgrowth, an inhibition that is strongly decreased on myelin deficient in Mag, Rtn4 and Omg (PubMed:22406547). Mice lacking both Rtn4r and Rtn4rl1 show increased axon regeneration after injury; the same effect is observed when Rtn4r, Rtn4rl1 and Rtn4rl2 are disrupted (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs further increases axon regeneration after injury (PubMed:22406547). Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 and combined disruption of Rtn4r and Rtn4rl2 have no effect on axon regeneration (PubMed:22406547).|||Perikaryon http://togogenome.org/gene/10090:Usp8 ^@ http://purl.uniprot.org/uniprot/Q80U87 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Cell membrane|||Cytoplasm|||Endosome membrane|||Forms a ternary complex with RNF128 and OTUB1. Interacts (via C-terminal UCH catalytic domain) with OTUB1 isoform 1. Interacts with STAM2 (via SH3 domain). Interacts with DNAJB3, EGFR, EPS15, RASGRF1, RNF41, YWHAE, YWHAG and YWHAZ. Interacts with NBR1, RASGRF1, RNF41 and IST1 (By similarity). Associates with the ESCRT-0 complex and with microtubules. Interacts with BIRC6/bruce and KIF23/MKLP1.|||Highly expressed in testis. Expressed at intermediate level in brain.|||Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1 (By similarity). Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (By similarity).|||Nucleus|||Phosphorylation of Ser-680 is essential for interaction with YWHAE and for cytosol localization. Undergoes dephosphorylation at Ser-680 in the M phase. Tyrosine-phosphorylated in its N-terminal half in an EGFR-dependent manner.|||The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.|||The rhodanese domain is sufficient for RNF41-binding.|||Ubiquitinated. Inactive form is mostly monoubiquitinated, but polyubiquitination happens too. Ubiquitination is increased in EGF-stimulated cells. Ubiquitination of active form is undetectable, suggesting a possibility that USP8 deubiquitinates itself, thereby regulating its own function. http://togogenome.org/gene/10090:H2-Ab1 ^@ http://purl.uniprot.org/uniprot/P14483|||http://purl.uniprot.org/uniprot/Q3TD53|||http://purl.uniprot.org/uniprot/Q8BPA0 ^@ PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane|||Ubiquitinated in immature dendritic cells leading to down-regulation of MHC class II. http://togogenome.org/gene/10090:Ptp4a3 ^@ http://purl.uniprot.org/uniprot/E9PXS4|||http://purl.uniprot.org/uniprot/Q9D658 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||Cell membrane|||Down-regulated upon skeletal muscle denervation.|||Early endosome|||Endosome|||Farnesylated. Farnesylation is required for membrane targeting. Unfarnesylated forms are shifted into the nucleus.|||Inhibited by sodium orthovanadate and peroxovanadium compounds, and by pentamidine.|||Interacts with tubulin.|||Present in the small intestine, where it is located in the differentiated epithelial cells of the villus but not in the proliferating crypt cells (at protein level). Expressed in heart and skeletal muscle, and at lower levels in lung, spleen and testis.|||Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II. http://togogenome.org/gene/10090:Or10a3 ^@ http://purl.uniprot.org/uniprot/Q8VEW1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Btg2 ^@ http://purl.uniprot.org/uniprot/Q04211|||http://purl.uniprot.org/uniprot/Q3TF68 ^@ Function|||Induction|||PTM|||Similarity|||Subunit ^@ Anti-proliferative protein; the function is mediated by association with deadenylase subunits of the CCR4-NOT complex. Activates mRNA deadenylation in a CNOT6 and CNOT7-dependent manner. In vitro can inhibit deadenylase activity of CNOT7 and CNOT8. Involved in cell cycle regulation. Could be involved in the growth arrest and differentiation of the neuronal precursors. Modulates transcription regulation mediated by ESR1. Involved in mitochondrial depolarization and neurite outgrowth (By similarity).|||Belongs to the BTG family.|||By nerve growth factor and tumors promoters.|||Interacts with PRKCABP. Interacts with CNOT7 and CNOT8; indicative for an association with the CCR4-NOT complex. Interacts with PIN1, inducing mitochondrial depolarization (By similarity).|||Phosphorylated at Ser-147 by MAPK1/ERK2 and MAPK3/ERK1, and at Ser-149 by MAPK14, leading to PIN1-binding and mitochondrial depolarization. http://togogenome.org/gene/10090:Il24 ^@ http://purl.uniprot.org/uniprot/A0A7R8GUW9|||http://purl.uniprot.org/uniprot/Q925S4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the IL-10 family.|||By IL4.|||Glycosylated.|||IL24-deficient mice are more sensitive to CCL4-induced liver injury than WT counterparts.|||Immune regulatory cytokine.|||Multifunctional cytokine mainly produced by T-cells that plays a regulatory role in immune response, tissue homeostasis, host defense, and oncogenesis (PubMed:31907348, PubMed:35148201). Possesses antiviral functions and induces the type I intereferon response during influenza infection. Signals through two receptor complexes IL20RA/IL20RB or IL20RB/IL22RA1. In turn, stimulates the JAK1-STAT3 and MAPK pathways and promotes the secretion of pro-inflammatory mediators including IL8 and MMP1 (By similarity). Intracellularly, maintains endoplasmic reticulum homeostasis by restricting the eIF2alpha-CHOP pathway-mediated stress signal (PubMed:31907348). In addition, acts as a quality control mechanism for the ubiquitin proteasome system by alerting the cell to proteasome dysfunction through activation of PKR/EIF2AK2 (PubMed:35148201).|||Secreted|||Selectively expressed by Th2 cells (PubMed:11342597). Expressed in the liver (PubMed:31907348).|||Ubiquitination at Lys-97 promotes proteasomal degradation. http://togogenome.org/gene/10090:Plpbp ^@ http://purl.uniprot.org/uniprot/Q544R1|||http://purl.uniprot.org/uniprot/Q6P8V7|||http://purl.uniprot.org/uniprot/Q9Z2Y8 ^@ Function|||Similarity ^@ Belongs to the pyridoxal phosphate-binding protein YggS/PROSC family.|||Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6. http://togogenome.org/gene/10090:Med31 ^@ http://purl.uniprot.org/uniprot/Q9CXU1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 31 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or5an6 ^@ http://purl.uniprot.org/uniprot/Q8VFV4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Localized in the dorsomedial and ventral region of the olfactory bulb.|||Odorant receptor involved in the detection of muscone. http://togogenome.org/gene/10090:Htatip2 ^@ http://purl.uniprot.org/uniprot/Q9Z2G9 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Mice are haploinsufficient for tumor suppression. 50% develop tumors within their second year. 30% of the tumors are hepatocellular carcinomas.|||Monomer. Binds nuclear transport receptors XPO4, IPO5/RANBP5, IPO7, IPO9 and KPNB1 as well as GCN1L1/GCN1 and LRPPRC probably through their HEAT repeats. Binds NCOA5/CIA (By similarity).|||Nucleus envelope|||Oxidoreductase required for tumor suppression. NADPH-bound form inhibits nuclear import by competing with nuclear import substrates for binding to a subset of nuclear transport receptors. May act as a redox sensor linked to transcription through regulation of nuclear import. http://togogenome.org/gene/10090:Pramel19 ^@ http://purl.uniprot.org/uniprot/L7MTS5 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Sbno1 ^@ http://purl.uniprot.org/uniprot/B2RRI2 ^@ Similarity ^@ Belongs to the SBNO family. http://togogenome.org/gene/10090:Hccs ^@ http://purl.uniprot.org/uniprot/P53702|||http://purl.uniprot.org/uniprot/Q8BP79 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome c-type heme lyase family.|||Lyase that catalyzes the covalent linking of the heme group to the cytochrome C apoprotein to produce the mature functional cytochrome.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Erf ^@ http://purl.uniprot.org/uniprot/A0A0R4J0I0|||http://purl.uniprot.org/uniprot/P70459 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ETS family.|||Expressed along the osteogenic margins of the developing calvarial bones, in a similar distribution to that observed for the master osteogenic regulator RUNX2.|||Expressed throughout embryonic development and adulthood. In the developing placenta, after 7.5 dpc expression is restricted to the extraembryonic ectoderm, and after 9.5 dpc to subpopulation of labyrinth cells.|||Mice fail to undergo chorioallantoic attachment and labyrinth development and die in utero due to severe placenta defects.|||Nucleus|||Phosphorylated by multiple kinases including MAPK1/ERK2 at THR-529. Phosphorylation regulates the activity of ERF (By similarity).|||Potent transcriptional repressor that binds to the H1 element of the Ets2 promoter. May regulate other genes involved in cellular proliferation (By similarity). Required for extraembryonic ectoderm differentiation, ectoplacental cone cavity closure, and chorioallantoic attachment. May be important for regulating trophoblast stem cell differentiation. http://togogenome.org/gene/10090:Ppp1r18 ^@ http://purl.uniprot.org/uniprot/Q8BQ30 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with Protein phosphatase 1 (PP1).|||May target protein phosphatase 1 to F-actin cytoskeleton.|||cytoskeleton http://togogenome.org/gene/10090:Igsf10 ^@ http://purl.uniprot.org/uniprot/Q3V1M1 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ In the embryo, expressed in the nasal mesenchyme.|||Involved in the control of early migration of neurons expressing gonadotropin-releasing hormone (GNRH neurons) (PubMed:27137492). May be involved in the maintenance of osteochondroprogenitor cells pool (By similarity).|||Secreted http://togogenome.org/gene/10090:Npc1 ^@ http://purl.uniprot.org/uniprot/O35604|||http://purl.uniprot.org/uniprot/Q7TMD4 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cysteine-rich N-terminal domain and a C-terminal domain containing a di-leucine motif necessary for lysosomal targeting are critical for mobilization of cholesterol from lysosomes.|||Belongs to the patched family.|||Defects in Npc1 cause a lysosomal storage disorder characterized by accumulation of cholesterol in lysosomes and impaired cholesterol homeostasis. Causes age-dependent loss of Purkinje cells, loss of body weight and leads then to ataxia and premature death at a median age of 72 days.|||Detected in liver (at protein level) (PubMed:21896731, PubMed:22048958). Ubiquitous (PubMed:9211850). Detected in adult heart, spleen, lung, liver, skeletal muscle, kidney, testis (PubMed:9211850).|||Interacts (via the second lumenal domain) with NPC2 (PubMed:22065762, PubMed:27551080). Interacts with TMEM97. Interacts with TIM1 (By similarity). Interacts with SLC38A9; this interaction inhibits cholesterol-mediated mTORC1 activation via its sterol transport activity (By similarity).|||Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment (PubMed:21896731, PubMed:22048958, PubMed:27551080). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket (By similarity). May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals (Probable). Inhibits cholesterol-mediated mTORC1 activation throught its interaction with SLC38A9 (By similarity).|||Late endosome membrane|||Lysosome membrane|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Nprl3 ^@ http://purl.uniprot.org/uniprot/Q8BXG6|||http://purl.uniprot.org/uniprot/Q8VIJ8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway.|||As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway.|||Belongs to the NPR3 family.|||Lethality towards the end of gestation caused by a range of cardiac defects, including outflow tract abnormalities and ventricular-septal defects.|||Lysosome|||Lysosome membrane|||Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction of the GATOR complex with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) heterodimers. GATOR1 interacts with GPR155/LYCHOS; interaction takes place in presence of cholesterol and prevents interaction between GATOR1 and KICSTOR. http://togogenome.org/gene/10090:Tuba1a ^@ http://purl.uniprot.org/uniprot/P68369 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.|||Belongs to the tubulin family.|||Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488).|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.|||Nitration of Tyr-451 is irreversible and interferes with normal dynein intracellular distribution.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:1967194, PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).|||Ubiquitously expressed, although primarily in lung and brain.|||Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.|||cytoskeleton http://togogenome.org/gene/10090:Mup11 ^@ http://purl.uniprot.org/uniprot/A2BIM8|||http://purl.uniprot.org/uniprot/P04938|||http://purl.uniprot.org/uniprot/Q9CXU6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Major urinary proteins (Mups) bind pheromones, and thus stabilize them to allow slow release into the air from urine marks. May protect pheromones from oxidation. May also act as pheromones themselves. In this context, they play a role in the regulation of social behaviors, such as aggression, mating, pup-suckling, territory establishment and dominance (Probable). Binds the pheromone analog 2-sec-butyl-4,5-dihydrothiazole (SBT) in vitro (PubMed:25279835).|||Major urinary proteins (Mups) bind pheromones, and thus stabilize them to allow slow release into the air from urine marks. May protect pheromones from oxidation. May also act as pheromones themselves. In this context, they play a role in the regulation of social behaviors, such as aggression, mating, pup-suckling, territory establishment and dominance.|||Secreted http://togogenome.org/gene/10090:Iqsec2 ^@ http://purl.uniprot.org/uniprot/A4GZ26|||http://purl.uniprot.org/uniprot/D3Z6V7|||http://purl.uniprot.org/uniprot/E9QAD8|||http://purl.uniprot.org/uniprot/Q5DU25 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BRAG family.|||Cytoplasm|||Is a guanine nucleotide exchange factor for the ARF GTP-binding proteins. http://togogenome.org/gene/10090:Or1e23 ^@ http://purl.uniprot.org/uniprot/Q8VF79 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcyt2 ^@ http://purl.uniprot.org/uniprot/A2ABY3|||http://purl.uniprot.org/uniprot/Q3USD5|||http://purl.uniprot.org/uniprot/Q922E4 ^@ Disruption Phenotype|||Function|||Similarity ^@ Belongs to the cytidylyltransferase family.|||Ethanolamine-phosphate cytidylyltransferase that catalyzes the second step in the synthesis of phosphatidylethanolamine (PE) from ethanolamine via the CDP-ethanolamine pathway (PubMed:17325045). Phosphatidylethanolamine is a dominant inner-leaflet phospholipid in cell membranes, where it plays a role in membrane function by structurally stabilizing membrane-anchored proteins, and participates in important cellular processes such as cell division, cell fusion, blood coagulation, and apoptosis (PubMed:17325045).|||Homozygous knockout embryos die after implantation, prior to embryonic day 8.5. http://togogenome.org/gene/10090:R3hcc1 ^@ http://purl.uniprot.org/uniprot/Q8BSI6 ^@ Caution ^@ Ribosome profiling data indicate that translation initiates from the non-AUG (CUG) codon used here. http://togogenome.org/gene/10090:Itga1 ^@ http://purl.uniprot.org/uniprot/Q3V3R4|||http://purl.uniprot.org/uniprot/Q8BPT3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. Alpha-1 associates with beta-1 (By similarity). Interacts with RAB21 (By similarity). Interacts (via cytoplasmic domain) with PTPN2; activates PTPN2 phosphatase activity towards EGFR and negatively regulates EGF signaling (By similarity).|||Integrin alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth.|||Membrane|||The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. http://togogenome.org/gene/10090:Spaca6 ^@ http://purl.uniprot.org/uniprot/E9Q8Q8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SPACA6 family.|||Expression is first detected on postnatal day 21.|||Highly expressed in testis (PubMed:24275887, PubMed:32393636). Minor expression also detected in epididymis, seminal vesicle and ovary (PubMed:32393636). Predominantly expressed in testicular germ cells during spermiogenesis (PubMed:24275887). Most abundant in round spermatids and detected at lower levels in elongating spermatids (PubMed:24275887).|||Male infertility (PubMed:24275887, PubMed:32393636). Testis appearance, size and weight are normal and there is no effect on sperm morphology or motility but there is a failure of sperm-egg interaction and fusion (PubMed:24275887, PubMed:32393636). Spermatozoa undergo normal acrosomal reaction and can penetrate the zona pellucida but accumulate in the perivitelline space as they are unable to fuse with the egg plasma membrane to complete fertilization (PubMed:24275887, PubMed:32393636). No effect on amount or localization of sperm-egg fusion protein IZUMO1 (PubMed:32393636).|||Sperm protein required for fusion of sperm with the egg membrane during fertilization.|||acrosome membrane http://togogenome.org/gene/10090:Sntn ^@ http://purl.uniprot.org/uniprot/Q8C9X1 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 'Sentan' means 'tip' in Japanese.|||Belongs to the S-100 family.|||Expressed exclusively in ciliated epithelial cells. Detected in ciliated epithelium of trachea and oviduct (at protein level).|||Expression gradually increases during in vitro ciliogenesis.|||May be a component of the linker structure that bridges the ciliary membrane and peripheral singlet microtubules.|||cilium http://togogenome.org/gene/10090:Pcdha8 ^@ http://purl.uniprot.org/uniprot/Q91Y12 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tfap2d ^@ http://purl.uniprot.org/uniprot/Q91ZK0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AP-2 family.|||Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members.|||Expressed in both embryonic and newborn brain.|||Expression is first detected at 9.5 dpc in the central nervous system and the developing heart. The signal detected in heart persists through to 10.5 dpc. Diffusely expressed in developing brain at 10.5 dpc to 11.5 dpc, but by 13.5 dpc expression is mostly confined to the midbrain and forebrain. Also expressed in the spinal cord at 10.5 dpc, and in retinal epithelium from 13.5 dpc to 16.5 dpc. No signals detected in tissues such as the neural crest, facial mesenchyme, and limbs where other Tfap2 genes are expressed.|||Nucleus|||Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. http://togogenome.org/gene/10090:Jpt2 ^@ http://purl.uniprot.org/uniprot/Q3TM10|||http://purl.uniprot.org/uniprot/Q6PGH2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JUPITER family.|||Cytoplasm|||Monomer. Dimer. Interacts with TPCN1.|||Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein required for NAADP-evoked intracellular calcium release. Confers NAADP-sensitivity to the two pore channels (TPCs) complex. Enables NAADP to activate Ca(2+) release from the endoplasmic reticulum through ryanodine receptors.|||Nucleus http://togogenome.org/gene/10090:Rhbdf2 ^@ http://purl.uniprot.org/uniprot/Q80WQ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S54 family.|||Endoplasmic reticulum membrane|||Interacts with EGF (PubMed:21439629). Interacts (via cytoplasmic N-terminus) with FRMD8/iTAP; this interaction leads to mutual protein stabilization (PubMed:29897336). Interacts with ADAM17/TACE (By similarity).|||Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. http://togogenome.org/gene/10090:Slc31a2 ^@ http://purl.uniprot.org/uniprot/Q4KL43|||http://purl.uniprot.org/uniprot/Q9CPU9|||http://purl.uniprot.org/uniprot/Q9D524 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.|||Cytoplasmic vesicle membrane|||Does not function as a copper(1+) importer in vivo (PubMed:24167251). However, in vitro functions as low-affinity copper(1+) importer (By similarity). Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1 (PubMed:24167251).|||Endosome membrane|||Homozygous knockout mice lacking Slc31a2 grow normally, with no obvious developmental defects.|||Late endosome membrane|||Lysosome membrane|||Membrane|||Oligomer. Interacts with SLC31A1; this interaction stabilizes SLC31A2 and protects it from ubiquitination and the subsequent degradation.|||Recycling endosome membrane|||The N-terminal domain may be involved in Cu(2+) acquisition from potential degradation products of proteins in the lysosome.|||Ubiquitinated; ubiquitination and the subsequent proteasomal degradation are prevent by SLC31A1 that stabilizes it. http://togogenome.org/gene/10090:Ppp1r1c ^@ http://purl.uniprot.org/uniprot/Q8BKK4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein phosphatase inhibitor 1 family.|||Cytoplasm|||May increase cell susceptibility to TNF-induced apoptosis. http://togogenome.org/gene/10090:Ugp2 ^@ http://purl.uniprot.org/uniprot/Q3U548|||http://purl.uniprot.org/uniprot/Q91ZJ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UDPGP type 1 family.|||Cytoplasm|||Homooctamer.|||UTP--glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen. http://togogenome.org/gene/10090:Arrdc3 ^@ http://purl.uniprot.org/uniprot/Q7TPQ9 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors (PubMed:21982743). Plays a role in NEDD4-mediated ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2 degradation. May recruit NEDD4 to ADRB2. Alternatively, may function as adapter protein that does not play a major role in recruiting NEDD4 to ADRB2, but rather plays a role in a targeting ADRB2 to endosomes.|||Belongs to the arrestin family.|||Cell membrane|||Cytoplasm|||Detected in visceral fat, subcutaneous fat, brown fat and skeletal muscle, and at lower levels in kidney.|||Early endosome|||Endosome|||Interacts (via PPxY motifs) with NEDD4 (via WW domains). Interacts with ADRB2. Interacts with ADRB3. Interacts with HGS (via PPxY motifs). Does not bind TXN (thioredoxin). Interacts with ITCH.|||Lysosome|||Mice are born at the expected Mendelian rate, but there is important perinatal lethality and the majority do not survive till weaning. Mutant mice have considerably less body mass and accumulate less body fat than wild-type, in spite of normal food intake. Heterozygous mice display higher oxygen uptake, increased activity levels and higher energy expenditure than wild-type. In addition, they display increased expression of genes required for thermogenesis, increased activation of signaling cascades downstream of beta-adrenergic receptors, more rapid readjustment of body temperature when exposed to cold and increased heat production.|||Up-regulated by fasting. Transiently up-regulated during the differentiation of pre-adipocytes. http://togogenome.org/gene/10090:B4galt5 ^@ http://purl.uniprot.org/uniprot/Q3U7I0|||http://purl.uniprot.org/uniprot/Q9JMK0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 7 family.|||Catalyzes the synthesis of lactosylceramide (LacCer) via the transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) (PubMed:21057870, PubMed:23882130, PubMed:30114188). LacCer is the starting point in the biosynthesis of all gangliosides (membrane-bound glycosphingolipids) which play pivotal roles in the CNS including neuronal maturation and axonal and myelin formation (PubMed:30114188). Plays a role in the glycosylation of BMPR1A and regulation of its protein stability (PubMed:29415997). Essential for extraembryonic development during early embryogenesis (PubMed:20574042, PubMed:21057870).|||Golgi apparatus|||Golgi stack membrane|||Highest levels in heart, brain, liver and kidney with lower levels in spleen, lung and testis.|||In the brain, expression increases after birth.|||Membrane|||Single knockout mice show early embryonic lethality (PubMed:20574042). Mice with conditional knockout in embryonic fibroblasts are born normally, grow to adulthood without apparent abnormalities but have reduced glucosylceramide beta-1,4-galactosyltransferase activity (PubMed:30114188). Double knockout mice of B4GALT5 and B4GALT6 genes develop normally during embryogenesis and perinatal stage (PubMed:30114188). However, they show growth retardation and motor deficits with hindlimb dysfunction at 2 weeks of age, and they all die by 4 weeks of age (PubMed:30114188). Axonal and myelin formation are remarkably impaired in the spinal cords and increased immature neurons in the cerebral cortices seen (PubMed:30114188). Glucosylceramide beta-1,4-galactosyltransferase activity and major brain gangliosides are completely absent in brain (PubMed:30114188). Knockdown in subcutaneous adipose tissue alleviates insulin resistance and adipose tissue inflammation, increases adipogenesis in high-fat diet (HFD)-fed mice and ob/ob mice and reduces the glycosylation of BMPR1A (PubMed:29415997).|||Up-regulated in subcutaneous adipose tissue during obesity and diabetes (at protein level). http://togogenome.org/gene/10090:Ndufaf8 ^@ http://purl.uniprot.org/uniprot/A2AMZ4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with NDUFAF5.|||Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1). Required to stabilize NDUFAF5.|||Mitochondrion http://togogenome.org/gene/10090:Cds2 ^@ http://purl.uniprot.org/uniprot/A2AMQ5|||http://purl.uniprot.org/uniprot/Q6PBC0|||http://purl.uniprot.org/uniprot/Q8BX08|||http://purl.uniprot.org/uniprot/Q99L43 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDS family.|||Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (By similarity). Exhibits specificity for the nature of the acyl chains at the sn-1 and sn-2 positions in the substrate, PA and the preferred acyl chain composition is 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid (By similarity). Plays an important role in regulating the growth and maturation of lipid droplets which are storage organelles at the center of lipid and energy homeostasis (PubMed:26946540).|||Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol.|||Endoplasmic reticulum membrane|||Homodimer.|||Membrane|||Ubiquitous. Expressed in the ganglion cell layer and inner nuclear layer of the retina. http://togogenome.org/gene/10090:Ggct ^@ http://purl.uniprot.org/uniprot/Q9D7X8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the gamma-glutamylcyclotransferase family.|||Catalyzes the formation of 5-oxoproline from gamma-glutamyl dipeptides and may play a significant role in glutathione homeostasis. Induces release of cytochrome c from mitochondria with resultant induction of apoptosis.|||Homodimer. http://togogenome.org/gene/10090:Or10a48 ^@ http://purl.uniprot.org/uniprot/Q8VFZ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Irf2bpl ^@ http://purl.uniprot.org/uniprot/Q8K3X4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IRF2BP family.|||Interacts with CTNNB1.|||Nucleus|||Probable E3 ubiquitin protein ligase involved in the proteasome-mediated ubiquitin-dependent degradation of target proteins. Through the degradation of CTNNB1, functions downstream of FOXF2 to negatively regulate the Wnt signaling pathway. Probably plays a role in the development of the central nervous system and in neuronal maintenance (By similarity). Also acts as a transcriptional regulator of genes controlling female reproductive function. May play a role in gene transcription by transactivating GNRH1 promoter and repressing PENK promoter (By similarity). http://togogenome.org/gene/10090:Mcrip2 ^@ http://purl.uniprot.org/uniprot/Q9CQB2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MCRIP family.|||Interacts with DDX6. Interacts with MCRIP1.|||Nucleus|||Stress granule http://togogenome.org/gene/10090:Nploc4 ^@ http://purl.uniprot.org/uniprot/P60670|||http://purl.uniprot.org/uniprot/Q3UDU9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NPL4 family.|||Binds ubiquitinated proteins via its RanBP2-type zinc finger.|||Endoplasmic reticulum|||Heterodimer with UFD1. The heterodimer binds ubiquitinated proteins. The heterodimer binds to VCP and inhibits Golgi membrane fusion (By similarity). Interacts with ZFAND2B; probably through VCP (PubMed:24160817).|||Nucleus|||The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (By similarity).|||cytosol http://togogenome.org/gene/10090:Kcnn1 ^@ http://purl.uniprot.org/uniprot/A0A140T8Q8|||http://purl.uniprot.org/uniprot/Q9EQR3 ^@ Activity Regulation|||Function|||Miscellaneous|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel KCNN family. KCa2.1/KCNN1 subfamily.|||Forms a voltage-independent potassium channel activated by intracellular calcium (PubMed:11557517). Activation is followed by membrane hyperpolarization (PubMed:11557517). Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization (PubMed:11557517).|||Heterooligomer. The complex is composed of 4 channel subunits each of which binds to a calmodulin subunit which regulates the channel activity through calcium-binding (By similarity). Interacts with calmodulin.|||Highest expression in brain and liver with lower levels in heart, testis, kidney and colon. In colon, detected in smooth muscle cells. Expressed in atrial and ventricular myocytes with higher levels in atrial myocytes.|||Inhibited by bee venom neurotoxin apamin. Inhibited by d-tubocurarine and tetraethylammonium (TEA).|||Membrane|||Produced by alternative splicing events in which various combinations of the four 5' non-coding exons A, B1, B2 or C are joined directly to exon 3.2.|||Reduced calmodulin-binding.|||The poly-Glu region of KCNN1 is polymorphic and the number of Glu varies between strains (from 10 to 12). The repeat with 10 Glu residues (shown here) is found in BALB/c, DBA/2J, 129/SvJ, A/J, C3H/HeJ, BALB/cJ, BXD-31, SM/J, ST/BJ, FVB/NJ, NZB/B1NJ, CBA/J and CAST/Ei. http://togogenome.org/gene/10090:Or4c109 ^@ http://purl.uniprot.org/uniprot/A2ATG3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dapp1 ^@ http://purl.uniprot.org/uniprot/Q9QXT1 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with PtdIns(3,4,5)P3 and PLCG2.|||May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K.|||Membrane|||Phosphorylated on tyrosine residues.|||Upon B-cell activation. http://togogenome.org/gene/10090:Cblb ^@ http://purl.uniprot.org/uniprot/B9EKI5|||http://purl.uniprot.org/uniprot/Q3TTA7 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.|||By serum starvation.|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.|||E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (PubMed:29237719).|||Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL. Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated). Interacts with IFT20 (By similarity).|||Mice are fertile and grossly normal. However, they show a high sensitivity to autoimmune diseases and may develop a spontaneous generalized autoimmune disorder characterized by auto-antibody production, infiltration of activated T- and B-lymphocytes into various organs and parenchymal damage.|||Phosphorylated on tyrosine and serine residues upon TCR or BCR activation. Phosphorylated on Tyr-664 and Tyr-708 in adipocytes following insulin stimulation.|||The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.|||The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.|||The UBA domain interacts with poly-ubiquitinated proteins.|||This protein has one functional calcium-binding site. http://togogenome.org/gene/10090:Swap70 ^@ http://purl.uniprot.org/uniprot/Q6A028 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Not detected in the spleen of 1-week old mice. Detected from 2-weeks onwards and thereafter levels increase and then from 12-weeks onwards levels decline.|||Nucleus|||Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusion (By similarity).|||Spleen. Expressed only in B-cells that have been induced to switch to various Ig isotypes.|||The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding.|||The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70.|||Tyrosine-phosphorylated.|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Pramel15 ^@ http://purl.uniprot.org/uniprot/B1ARV6 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Kcna7 ^@ http://purl.uniprot.org/uniprot/Q17ST2 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.7/KCNA7 sub-subfamily.|||Detected in heart, skeletal muscle, brain, and pancreatic islet cells.|||Heterotetramer of potassium channel proteins.|||Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Channels formed by isoform 1 inactivate faster than channels formed by isoform 2.|||Membrane|||Produced by alternative initiation at Met-33 of isoform 1.|||The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Skic3 ^@ http://purl.uniprot.org/uniprot/F8VPK0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKI3 family.|||Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8. Interacts with PAF1.|||Component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways. The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation. SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling. In the nucleus, the SKI complex associates with transcriptionally active genes in a manner dependent on PAF1 complex (PAF1C).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Gfus ^@ http://purl.uniprot.org/uniprot/P23591|||http://purl.uniprot.org/uniprot/Q5HZI6 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family. Fucose synthase subfamily.|||Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction.|||Homodimer.|||Mutagen treatment of P815 tumor cells produces tum-variants that elicit a cytolytic T-lymphocyte response (CTL). The antigenic allele differs from the normal allele by a single mutation in position 139. http://togogenome.org/gene/10090:Pias2 ^@ http://purl.uniprot.org/uniprot/F8WHS8|||http://purl.uniprot.org/uniprot/G3UWE3|||http://purl.uniprot.org/uniprot/Q8C5D8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIAS family.|||Binds SUMO1 and UBE2I. Interacts with AXIN1, JUN, MDM2, PARK7, TP53 and TP73 isoform alpha, but not TP73 isoform beta. Interacts with STAT4 following IL12 and IFN-alpha stimulation of T-cells. Interacts also with GTF2I, GTF2IRD1, IKFZ1, DAB2 and MSX2, as well as with several steroid receptors, including ESR1, ESR2, NR3C1, PGR, AR, and with NCOA2. Sumoylation of a target protein seems to enhance the interaction. Binds to sumoylated ELK1. Interacts with PLAG1 (By similarity). Binds DNA, such as CDKN1A promoter, in a sequence-specific manner. Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase (By similarity). Interacts with IFIH1/MDA5 (By similarity). Interacts with PML (By similarity). Interacts with PRDM1 (By similarity).|||Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. The effects of this transcriptional coregulation, transactivation or silencing may vary depending upon the biological context and PIAS2 isoform studied. However, it seems to be mostly involved in gene silencing. Binds to sumoylated ELK1 and enhances its transcriptional activity by preventing recruitment of HDAC2 by ELK1, thus reversing SUMO-mediated repression of ELK1 transactivation activity. Isoform PIASx-beta, but not isoform PIASx-alpha, promotes MDM2 sumoylation. Isoform PIASx-alpha promotes PARK7 sumoylation. Isoform PIASx-beta promotes NCOA2 sumoylation more efficiently than isoform PIASx-alpha (By similarity). Sumoylates PML at'Lys-65' and 'Lys-160' (By similarity).|||Nucleus|||Nucleus speckle|||PML body|||Sumoylated.|||The LXXLL motif is a transcriptional coregulator signature. http://togogenome.org/gene/10090:Wnt7b ^@ http://purl.uniprot.org/uniprot/E9Q5E3|||http://purl.uniprot.org/uniprot/P28047|||http://purl.uniprot.org/uniprot/Q6NZR1|||http://purl.uniprot.org/uniprot/Q6PDY6 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 7.5 and 8.5 dpc, detected in extraembryonic membranes and cells that form the chorionic plate.|||Belongs to the Wnt family.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Interacts with FZD1 and FZD10 (PubMed:15923619). Interacts with FZD4 (in vitro) (PubMed:15923619). Interacts with PORCN (PubMed:10866835). Interacts with glypican GPC3 (By similarity). Interacts (via intrinsically disordered linker region) with RECK; interaction with RECK confers ligand selectivity for Wnt7 in brain endothelial cells and allows these cells to selectively respond to Wnt7 (By similarity).|||Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:15923619, PubMed:28803732). Required for normal fusion of the chorion and the allantois during placenta development (PubMed:11543617). Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (PubMed:28803732).|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||The intrinsically disordered linker region is required for recognition by RECK in brain endothelial cells.|||extracellular matrix http://togogenome.org/gene/10090:Khnyn ^@ http://purl.uniprot.org/uniprot/Q80U38 ^@ Similarity ^@ Belongs to the N4BP1 family. http://togogenome.org/gene/10090:Tas2r120 ^@ http://purl.uniprot.org/uniprot/Q7M721 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Naip6 ^@ http://purl.uniprot.org/uniprot/Q9JIB6 ^@ Function|||Subunit ^@ (Microbial infection) Interacts with S.typhimurium (Salmonella) flagellin.|||Component of the NLRC4 inflammasome, at least composed of NLRC4, caspase-1 (CASP1) and some NAIP protein.|||Sensor component of the NLRC4 inflammasome that specifically recognizes and binds flagellin from pathogenic bacteria. Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (PubMed:21874021). The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri. May contribute to prevent motor-neuron apoptosis induced by a variety of signals (By similarity). http://togogenome.org/gene/10090:Knop1 ^@ http://purl.uniprot.org/uniprot/Q9Z2Q2 ^@ Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated during myoblast differentiation.|||Expressed in testis.|||Interacts with ZNF106.|||nucleolus http://togogenome.org/gene/10090:Gm20737 ^@ http://purl.uniprot.org/uniprot/Q3TTD8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Cotl1 ^@ http://purl.uniprot.org/uniprot/Q9CQI6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin-binding proteins ADF family. Coactosin subfamily.|||Binds to F-actin in a calcium-independent manner. Has no direct effect on actin depolymerization. Acts as a chaperone for ALOX5 (5LO), influencing both its stability and activity in leukotrienes synthesis (By similarity).|||Cytoplasm|||Interacts with 5-lipoxygenase (ALOX5/5LO) in a calcium-independent manner. Binds to F-actin with a stoichiometry of 1:2 (By similarity).|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:H2ac7 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Ak7 ^@ http://purl.uniprot.org/uniprot/Q9D2H2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ In the C-terminal section; belongs to the dpy-30 family.|||In the central section; belongs to the adenylate kinase family.|||Mutant mice present pathological signs characteristic of primary ciliary dyskinesia (PCD), including high prevalence of microtubular defects, significantly decreased ciliary beat frequency, hydrocephalus, abnormal spermatogenesis, mucus accumulation in the paranasal passages, and exacerbated respiratory responses upon allergen challenge. This phenotype arose serendipitously in the process of generating transgenic mice harboring a heme oxygenase 1 construct, due to the serendipitous disruption of Ak7 locus by the transgene insertion event (PubMed:18776131). Mutant testes reveal the absence of flagellum structures, compared with those from control littermates. In mutant testes, nearly all sperm heads are attached to cytoplasmic mass and not prolonged by flagellar structures, such as mitochondrial sheath, fibrous sheath and axoneme. In mutant epididymes, very few sperm structures are observed. The rare sperm flagellum observed show an absence of the central pair of microtubules (PubMed:29365104).|||Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. Also displays broad nucleoside diphosphate kinase activity. Involved in maintaining ciliary structure and function.|||cytosol|||flagellum http://togogenome.org/gene/10090:Sumo2 ^@ http://purl.uniprot.org/uniprot/P61957 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin family. SUMO subfamily.|||Cleavage of precursor form by SENP1 or SENP2 is necessary for function.|||Interacts with SAE2 and UBE2I. Interacts with ZNF451. Identified in a complex with ZNF451 and UBE2I/UBC9, where one ZNF451 interacts with one UBE2I/UBC9 and two SUMO2 chains, one bound to the UBE2I/UBC9 active site and the other to another region of the same UBE2I/UBC9 molecule. Covalently attached to a number of proteins. Interacts with PELP1. Interacts with USP25; the interaction sumoylates USP25. Interacts with SIMC1, CASP8AP2, RNF111 and SOBP (via SIM domains). Interacts with MTA1. Interacts with HINT1 (PubMed:31088288). Interacts with GCNA (via SIM domains); this interaction allows the GCNA recruitment to DPCs sites (By similarity).|||Monoubiquitinated N-terminally by UBE2W, which primes it for RNF4-dependent polyubiquitination by the UBE2V1-UBE2N heterodimer.|||Nucleus|||PML body|||Polymeric chains can be formed through Lys-11 cross-linking. Polymeric SUMO2 chains undergo 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 (By similarity).|||Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. Plays a role in the regulation of sumoylation status of SETX (By similarity). http://togogenome.org/gene/10090:Hip1r ^@ http://purl.uniprot.org/uniprot/Q9JKY5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLA2 family.|||Binds F-actin via the talin-like I/LWEQ domain.|||Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis.|||Endomembrane system|||Hip1 and Hip1r double knockout mice are dwarfed, afflicted with severe vertebral defects and die in early adulthood.|||Homodimer (PubMed:18790740). Interacts with actin; homodimerization promotes actin binding (PubMed:18790740). Interacts with CLTB (By similarity). Interacts with HIP1 (By similarity). Interacts (via ENTH and I/LWEQ domains) with BCL2L10 (By similarity).|||Widely expressed. Expressed at lower levels in skeletal muscle and heart. The level of expression does not change appreciably during development.|||clathrin-coated vesicle membrane|||perinuclear region http://togogenome.org/gene/10090:Slc25a40 ^@ http://purl.uniprot.org/uniprot/Q8BGP6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Cells lacking both Slc25a39 and Slc25a40 show defects in the activity and stability of proteins containing iron-sulfur clusters.|||Mitochondrion inner membrane|||Probable mitochondrial transporter required for glutathione import into mitochondria. Glutathione, which plays key roles in oxidative metabolism, is produced exclusively in the cytosol and is imported in many organelles (By similarity). Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters, as well as erythropoiesis (PubMed:34707288). http://togogenome.org/gene/10090:Or52s1 ^@ http://purl.uniprot.org/uniprot/Q8VF28 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pts ^@ http://purl.uniprot.org/uniprot/Q9R1Z7 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subunit ^@ Belongs to the PTPS family.|||Binds 1 zinc ion per subunit.|||Homodimer (PubMed:9894812). Homohexamer formed of two homotrimers in a head to head fashion.|||Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.|||Phosphorylation of Ser-18 is required for maximal enzyme activity.|||The active site is at the interface between 2 subunits. The proton acceptor Cys is on one subunit, and the charge relay system is on the other subunit. http://togogenome.org/gene/10090:Gm20773 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXW2 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Prdx3 ^@ http://purl.uniprot.org/uniprot/P20108 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accelerates decline of physical strength; at the age of 10 months, the physical strength is much lower than in the wild-type littermate (PubMed:27037278). Increased oxidative damage and decreased mitochondrial DNA copy number in skeletal muscles (PubMed:27037278). Increased apoptotic cells in the brain (PubMed:27037278).|||Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.|||Cytoplasm|||Early endosome|||Expression is increased after induction of MEL cells to differentiation by DMSO.|||Homodimer; disulfide-linked, upon oxidation. 6 homodimers assemble to form a ring-like dodecamer. Interacts with NEK6. Interacts with LRRK2. Interacts with MAP3K13 (By similarity). Interacts with RPS6KC1 (via PX domain).|||Housekeeping-type gene preferentially expressed in murine erythroleukemia (MEL) cells.|||Mitochondrion|||Phosphorylated by LRRK2; phosphorylation reduces perodixase activity.|||S-palmitoylated.|||The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.|||The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) and sulphonic acid (C(P)-SO3H) instead of its condensation to a disulfide bond.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides. Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol (By similarity). Required for the maintenance of physical strength (PubMed:27037278). http://togogenome.org/gene/10090:Rasa3 ^@ http://purl.uniprot.org/uniprot/Q60790 ^@ Function|||Tissue Specificity ^@ High levels in brain, lower in spleen and lung.|||Inhibitory regulator of the Ras-cyclic AMP pathway. May bind inositol tetrakisphosphate (IP4). http://togogenome.org/gene/10090:Stfa2l1 ^@ http://purl.uniprot.org/uniprot/Q8BWM3 ^@ Similarity ^@ Belongs to the cystatin family. http://togogenome.org/gene/10090:Susd1 ^@ http://purl.uniprot.org/uniprot/E9Q3H4 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Ankar ^@ http://purl.uniprot.org/uniprot/A2RT91 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Grap2 ^@ http://purl.uniprot.org/uniprot/O89100 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GRB2/sem-5/DRK family.|||Cytoplasm|||Endosome|||Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.|||Interacts with phosphorylated LAT and LAX1 upon TCR activation. Interacts with SHB. Interacts with PTPN23 (By similarity). Interacts with phosphorylated LIME1 upon TCR activation.|||Nucleus http://togogenome.org/gene/10090:Fnbp4 ^@ http://purl.uniprot.org/uniprot/Q6ZQ03 ^@ Developmental Stage|||Domain|||Induction|||Subunit|||Tissue Specificity ^@ Binds FMN1. Interacts with the Arg/Gly-rich-flanked Pro-rich regions of KHDRBS1/SAM68. Arginine methylation in these regions has no effect on this binding (By similarity).|||First detected at 9 dpc.|||These WW domains interact with Arg/Gly-rich-flanked Pro-rich domains found in several WW domain-binding proteins (WBPs). The N-terminal WW domain has the greater ligand-binding ability (By similarity).|||Ubiquitous. Highest levels in spleen and thymus.|||Up-regulated by p53. http://togogenome.org/gene/10090:Or5g23 ^@ http://purl.uniprot.org/uniprot/Q7TR99 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tdpoz7 ^@ http://purl.uniprot.org/uniprot/E0CYU8 ^@ Similarity ^@ Belongs to the Tdpoz family. http://togogenome.org/gene/10090:Rapgef4 ^@ http://purl.uniprot.org/uniprot/Q9EQZ6 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in cerebellum, pituitary, adrenal gland and liver.|||Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2.|||Interacts with RAP1B, RIMS1 and RIMS2. Probably part of a complex with RIMS2 and GTP-activated RAB3A.|||Membrane|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||The DEP domain is involved in membrane localization independent from regulation by cAMP.|||The N-terminal nucleotide phosphate binding region cAMP 1 has a much lower affinity for cAMP as compared to cAMP 2. http://togogenome.org/gene/10090:Klf12 ^@ http://purl.uniprot.org/uniprot/O35738 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Confers strong transcriptional repression to the AP-2-alpha gene. Binds to a regulatory element (A32) in the AP-2-alpha gene promoter.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF12, the motif is inactive. http://togogenome.org/gene/10090:Nit1 ^@ http://purl.uniprot.org/uniprot/Q8VDK1 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ According to Rosetta Stone theory, the existence of a fusion protein in one genome predicts that the separate polypeptides expressed in other organisms function in the same cellular or biochemical pathway. In Drosophila melanogaster and Caenorhabditis elegans, NitFhit is a fusion protein composed of a C-terminal Fhit domain and a domain related to plant and bacterial nitrilase.|||Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.|||Catalyzes the hydrolysis of the amide bond in N-(4-oxoglutarate)-L-cysteinylglycine (deaminated glutathione), a metabolite repair reaction to dispose of the harmful deaminated glutathione. Possesses amidase activity toward deaminated ophthalmate in vitro (PubMed:28373563). Plays a role in cell growth and apoptosis: loss of expression promotes cell growth, resistance to DNA damage stress and increased incidence to NMBA-induced tumors. Has tumor suppressor properties that enhances the apoptotic responsiveness in cancer cells; this effect is additive to the tumor suppressor activity of FHIT. It is also a negative regulator of primary T-cells.|||Cytoplasm|||Expressed in most tissues with higher expression in adult liver and kidney as well as in fetal adrenal gland and skeletal muscle.|||Mice are normal at birth as well as during growth. Mammary glands exhibit an increase in ductal and alveolar structures as well as more cyclin-D1 positive cells in mid-pregnancy. In the basal layer of epidermis, the number of cyclin-D1 positive cells is also higher. No lymphoid malignancy is observed. Kidney cells lacking Nit1 exhibit round and compact shapes, loss of lobular structure, higher cell density with increased S and G2/M cell populations. Cyclin D1 expression is increased, whereas differences in the other cell cycle-associated proteins appeared minimal. T-cells lacking NIT-1 display enhanced proliferation, elevated activation marker expression, accelerated cell cycle progression and aberrant expression of some cell cycle proteins.|||Mitochondrion http://togogenome.org/gene/10090:Tubb2a ^@ http://purl.uniprot.org/uniprot/Q7TMM9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity (By similarity). Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with ZNRF1.|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Or2r3 ^@ http://purl.uniprot.org/uniprot/Q8VGP5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm4922 ^@ http://purl.uniprot.org/uniprot/Q8C0N0 ^@ Function|||Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Smok subfamily.|||May play a role in sperm motility, especially in the regulation of flagellar function. http://togogenome.org/gene/10090:Slc39a4 ^@ http://purl.uniprot.org/uniprot/Q78IQ7 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Highly expressed in the small intestine and embryonic visceral yolk sac. Weakly expressed in the stomach and liver.|||Homodimer (PubMed:30593504). Homodimerization is mediated by the transmembrane domain (By similarity).|||Knockout mice die in utero during early development. Mice heterozygous for a null allele exhibit developmental defects similar to the teratology of zinc deficiency (PubMed:17483098). Slc39a4-intestine knockout mice reveal that total zinc is dramatically and rapidly decreased in these organs whereas iron, manganese, and copper slowly accumulated to high levels in the liver as the disease progressed. Defect in zinc uptake are followed by a switch from anabolic to catabolic metabolism in the mouse leading to dramatic weight loss, dyshomeostasis of several essential metals and ultimately lethality in the absence of excess dietary zinc (PubMed:22737083).|||N-glycosylated.|||Recycling endosome membrane|||Selective transporter that mediates the uptake of Zn(2+) (PubMed:14709598, PubMed:14612438, PubMed:12801924). Plays an essential role for dietary zinc uptake from small intestine (PubMed:12801924). The Zn(2+) uniporter activity is regulated by zinc availability (By similarity). Exhibits also polyspecific binding and transport of Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations (PubMed:12801924).|||The extracellular N-terminal ectodomain is cleaved when cells are Zn(2+) deficient, N-terminally cleaved SLC39A4 is then internalized faster.|||The two metal binding sites M1 and M2 that are halfway through the membrane form a binuclear metal center. M1 is essential to Zn(2+) transport, while the other, M2 appears to have an auxiliary role presumably by acting as an additional transport site that can modulate the properties of the primary transport site. The binuclear metal center plays a key role in Zn(2+) sensing.|||Under excess Zn(2+) conditions, SLC39A4 on the cell surface is rapidly endocytosed, ubiquitinated, and degraded.|||Up-regulated under conditions of dietary zinc deficiency. Down-regulated under conditions of dietary zinc excess. http://togogenome.org/gene/10090:Blcap ^@ http://purl.uniprot.org/uniprot/P62951 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BLCAP family.|||May regulate cell proliferation and coordinate apoptosis and cell cycle progression via a novel mechanism independent of both p53/TP53 and NF-kappa-B.|||Membrane http://togogenome.org/gene/10090:Pcdhga2 ^@ http://purl.uniprot.org/uniprot/Q91XY6 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Fam135b ^@ http://purl.uniprot.org/uniprot/Q9DAI6 ^@ Similarity ^@ Belongs to the FAM135 family. http://togogenome.org/gene/10090:Adamts14 ^@ http://purl.uniprot.org/uniprot/B2RXX5 ^@ Caution|||Cofactor|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular matrix http://togogenome.org/gene/10090:Mtrex ^@ http://purl.uniprot.org/uniprot/Q9CZU3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated when MTREX is incorporated into NEXT complex an the nuclear RNA exosome complex.|||Belongs to the helicase family. SKI2 subfamily.|||Catalyzes the ATP-dependent unwinding of RNA duplexes with a single-stranded 3' RNA extension. Central subunit of many protein complexes, namely TRAMP-like, nuclear exosome targeting (NEXT) and poly(A) tail exosome targeting (PAXT). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs. PAXT directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor ZCCHC8, which links to RNA-binding protein adapters. Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA. May be involved in pre-mRNA splicing. In the context of NEXT complex can also in vitro unwind DNA:RNA heteroduplexes with a 3' poly (A) RNA tracking strand. Can promote unwinding and degradation of structured RNA substrates when associated with the nuclear exosome and its cofactors. Can displace a DNA strand while translocating on RNA to ultimately degrade the RNA within a DNA/RNA heteroduplex (By similarity). Plays a role in DNA damage response (By similarity).|||Component of a TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes. Identified in the spliceosome C complex. Component of the poly(A) tail exosome targeting (PAXT) complex made of PABPN1, ZFC3H1 and MTREX that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation. Interacts with ZCCHC8; this interaction bridges the interaction between RBM7 and MTREX. Binds to ZFC3H1 and RBM7 in a RNase-insensitive manner. Interacts with EXOSC10; the interaction mediates the association of MTREX with nuclear RNA exosomes. Interacts with isoform 1 of NVL in an ATP-dependent manner; the interaction is required to associate NVL with nuclear RNA exosome. Interacts with WDR74; the interaction dissociation in a late stage of rRNA synthesis is required for appropriate maturation of pre-60S particles and depends on the ATPase activity of NVL. Interacts with MPHOSPH6. Interacts with the RNA cap-binding complex proteins NCBP1 and SRRT. Interacts with NRDE2; the interaction is direct and negatively regulates MTREX function in exosomal degradation by changing its conformation precluding interaction with ZFC3H1, the RNA cap-binding complex proteins NCBP1 and SRRT, and association with the exosome. Interacts with the nuclear RNA exosome complex.|||Nucleus|||Nucleus speckle|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Bivm ^@ http://purl.uniprot.org/uniprot/Q8CBX9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BIVM family.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Tmem82 ^@ http://purl.uniprot.org/uniprot/Q8R115 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM82 family.|||Membrane http://togogenome.org/gene/10090:Nudt6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J176|||http://purl.uniprot.org/uniprot/Q3ULU4|||http://purl.uniprot.org/uniprot/Q8CH40|||http://purl.uniprot.org/uniprot/Q8CH41 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Nudix hydrolase family.|||Cytoplasm|||May contribute to the regulation of cell proliferation.|||Mitochondrion|||Monomer and homodimer.|||Nucleus|||This protein is coded from a FGF2 (BFGF) gene antisense transcript. http://togogenome.org/gene/10090:Ribc1 ^@ http://purl.uniprot.org/uniprot/Q9D0B8 ^@ Similarity ^@ Belongs to the RIB43A family. http://togogenome.org/gene/10090:Zfp329 ^@ http://purl.uniprot.org/uniprot/Q6GQR8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Prl7a1 ^@ http://purl.uniprot.org/uniprot/O54830 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed specifically in the placenta. Detected only in the trophoblast giant cells.|||Highest expression at mid-pregnancy.|||Secreted http://togogenome.org/gene/10090:Krtap19-4 ^@ http://purl.uniprot.org/uniprot/Q925H7 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 19 family.|||Expression in skin and hair follicle is regulated by HOXC13 and by GATA3.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins.|||Strong expression in narrowly defined pattern restricted to the lower and middle cortical regions of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). http://togogenome.org/gene/10090:Rnasek ^@ http://purl.uniprot.org/uniprot/Q8K3C0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase K family.|||Endomembrane system|||Endoribonuclease which preferentially cleaves ApU and ApG phosphodiester bonds. Hydrolyzes UpU bonds at a lower rate (By similarity). Regulates the activity of vacuolar (H+)-ATPase (V-ATPase) which is responsible for acidifying and maintaining the pH of intracellular compartments (By similarity). Required at an early stage of receptor-mediated endocytosis (By similarity).|||Interacts with the proton translocation complex V0 of the V-ATPase (By similarity). Interacts with ATP6AP1 (By similarity).|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Nmrk2 ^@ http://purl.uniprot.org/uniprot/Q9D7C9 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the uridine kinase family. NRK subfamily.|||Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). Reduces laminin matrix deposition and cell adhesion to laminin, but not to fibronectin. Involved in the regulation of PXN at the protein level and of PXN tyrosine phosphorylation. May play a role in the regulation of terminal myogenesis (By similarity).|||Down-regulated during myoblast differentiation.|||Expressed in skeletal muscle (at protein level).|||Monomer (By similarity). Interacts with ITGB1 alone or when associated with alpha-7, but not with alpha-5. http://togogenome.org/gene/10090:Cpa4 ^@ http://purl.uniprot.org/uniprot/Q6P8K8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Interacts with LXN.|||Metalloprotease that could be involved in the histone hyperacetylation pathway. Releases a C-terminal amino acid, with preference for -Phe, -Leu, -Ile, -Met, -Tyr and -Val.|||Secreted http://togogenome.org/gene/10090:Gtf2e1 ^@ http://purl.uniprot.org/uniprot/Q9D0D5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIE alpha subunit family.|||Nucleus|||Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase.|||Tetramer of two alpha and two beta chains. Interacts with TAF6/TAFII80. Interacts with ATF7IP. Interacts with SND1. http://togogenome.org/gene/10090:Qng1 ^@ http://purl.uniprot.org/uniprot/G3X8U3 ^@ Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the QNG1 protein family.|||Catalyzes the hydrolysis of queuosine 5'-phosphate, releasing the nucleobase queuine (q). Is required for salvage of queuine from exogenous queuosine (Q) that is imported and then converted to queuosine 5'-phosphate intracellularly.|||Eukaryotes lack the canonical genes for de novo biosynthesis of queuosine (Q), present in most bacteria. Therefore, this molecule must be sourced from ingested food and/or the gut microbiota, and metabolized to its corresponding nucleobase, queuine (q), before incorporation into cytoplasmic and mitochondrial tRNAs. Incorporation of q into the anticodon of some tRNAs contributes to translational efficiency and accuracy.|||Highly expressed in liver. http://togogenome.org/gene/10090:Ssh2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J2A0|||http://purl.uniprot.org/uniprot/Q5SW75 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||Complete male infertility but no effect on body weight or testis weight and size (PubMed:36942942). Impaired spermatogenesis devoid of spermatid elongation (arrested at stage II-III), resulting in accumulation of round spermatids with malformed acrosomal structures (PubMed:36942942). Spermatids and germ cells show increased levels of apoptosis via BCL2-caspase-3 pathway (PubMed:36942942). Actin cytoskeleton disorganization and actin filament aggregation in spermatids and germ cells, along with increased levels of cofilin phosphorylation (PubMed:36942942).|||Cytoplasm|||Expressed in brain, heart, liver, skeletal muscle, testis and thymus. Also expressed at lower levels in kidney, small intestine and spleen (PubMed:14531860). Within testicular seminiferous tubules expressed in germ cells and spermatocytes, where it has a cytoplasmic localization, and round spermatids, where it concentrates in the acrosomal region next to the nucleus (PubMed:36942942).|||Expressed in the nervous system at 14.5 dpc (PubMed:14531860). Undetectable in testes at 7 days after birth (PubMed:36942942). Gradually increased expression between 14 and 35 days after birth followed by slightly decreased expression by 56 days after birth (at protein level) (PubMed:36942942).|||Interacts with filamentous actin.|||Intron retention.|||Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein (PubMed:14531860). Required for spermatogenesis (PubMed:36942942). Involved in acrosome biogenesis, probably by regulating cofilin-mediated actin cytoskeleton remodeling during proacrosomal vesicle fusion and/or Golgi to perinuclear vesicle trafficking (PubMed:36942942).|||Tyrosine phosphatase activity has not been demonstrated for this protein to date.|||acrosome|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Ndufa2 ^@ http://purl.uniprot.org/uniprot/Q9CQ75 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Acetylation of Lys-64 and Lys-75 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the complex I NDUFA2 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Aven ^@ http://purl.uniprot.org/uniprot/Q9D9K3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds Apaf-1, BCL-2 and BAD (Bcl-xl).|||Endomembrane system|||Protects against apoptosis mediated by Apaf-1. http://togogenome.org/gene/10090:Lonp1 ^@ http://purl.uniprot.org/uniprot/Q8CGK3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. Endogenous substrates include mitochondrial steroidogenic acute regulatory (StAR) protein, DELE1, helicase Twinkle (TWNK) and the large ribosomal subunit protein MRPL32/bL32m. MRPL32/bL32m is protected from degradation by LONP1 when it is bound to a nucleic acid (RNA), but TWNK is not. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial promoters and RNA in a single-stranded, site-specific, and strand-specific manner. May regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters.|||Belongs to the peptidase S16 family.|||Detected in liver > heart > kidney > testis.|||Homohexamer. Organized in a ring with a central cavity. The ATP-binding and proteolytic domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers. DNA and RNA binding is stimulated by substrate and inhibited by ATP binding. Interacts with TWNK and mitochondrial DNA polymerase subunit POLG.|||Mitochondrion matrix http://togogenome.org/gene/10090:Prelid3a ^@ http://purl.uniprot.org/uniprot/Q8VE85 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the slowmo family.|||In vitro, the TRIAP1:PRELID3A complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space. Phosphatidic acid import is required for cardiolipin (CL) synthesis in the mitochondrial inner membrane.|||Interacts with TRIAP1.|||Mitochondrion http://togogenome.org/gene/10090:Wbp4 ^@ http://purl.uniprot.org/uniprot/Q61048 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the spliceosome B complex (PubMed:9724750). Associated with U2 snRNPs. Binds splicing factors SNRPB, SNRPC and SF1 (PubMed:9724750). Interacts via the WW domains with the Pro-rich domains of KHDRBS1/SAM68 (PubMed:10748127). Interacts via the WW domains with the Pro-rich domains of WBP11 (By similarity). Interacts with SNRNP200 (By similarity).|||Involved in pre-mRNA splicing as a component of the spliceosome. May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex.|||Nucleus|||Nucleus speckle|||The WW domain recognizes the proline, glycine and methionine-rich (PGM) motif present in the splicing factors, as well as the Arg/Gly-rich-flanked Pro-rich domains found in several WW domain-binding proteins. http://togogenome.org/gene/10090:Notch4 ^@ http://purl.uniprot.org/uniprot/P31695 ^@ Developmental Stage|||Disease Annotation|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOTCH family.|||Cell membrane|||Contaminating sequence. Sequence of unknown origin.|||Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). May regulate branching morphogenesis in the developing vascular system.|||Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH4.|||Highly expressed in endothelial cells during embryonic development from 9.0 dpc.|||Highly expressed in lung, moderately in heart kidney, and at lower levels in the ovary and skeletal muscle. A very low expression is seen in the brain, intestine, liver and testis.|||Loss of the extracellular domain causes constitutive activation of the Notch protein, which leads to hyperproliferation of glandular epithelial tissues and development of mammary carcinomas.|||Nucleus|||Phosphorylated.|||Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane. http://togogenome.org/gene/10090:Ptpa ^@ http://purl.uniprot.org/uniprot/P58389|||http://purl.uniprot.org/uniprot/Q543N6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with PP2A heterodimeric core enzyme PP2A(D), composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A) (By similarity). Interacts with PPP2CB (PubMed:12952889).|||Belongs to the PTPA-type PPIase family.|||Cytoplasm|||Nucleus|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A (By similarity). http://togogenome.org/gene/10090:C030006K11Rik ^@ http://purl.uniprot.org/uniprot/Q8VE95 ^@ Similarity ^@ Belongs to the UPF0598 family. http://togogenome.org/gene/10090:Brk1 ^@ http://purl.uniprot.org/uniprot/Q91VR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BRK1 family.|||Homotrimer when in free form. Directly interacts with WASF2. Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1 (By similarity).|||Involved in regulation of actin and microtubule organization. Part of a WAVE complex that activates the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (PubMed:27605705).|||cytoskeleton http://togogenome.org/gene/10090:Hmg20a ^@ http://purl.uniprot.org/uniprot/Q9DC33 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected at 16.5 dpc in the outer cortex of the developing brain.|||Expressed in brain. Detected in mature neurons.|||Interacts with DTNB.|||Nucleus|||Plays a role in neuronal differentiation as chromatin-associated protein. Acts as inhibitor of HMG20B. Overcomes the repressive effects of the neuronal silencer REST and induces the activation of neuronal-specific genes. Involved in the recruitment of the histone methyltransferase KMT2A/MLL1 and consequent increased methylation of histone H3 lysine 4. http://togogenome.org/gene/10090:Spata45 ^@ http://purl.uniprot.org/uniprot/Q9CVW4 ^@ Similarity ^@ Belongs to the SPATA45 family. http://togogenome.org/gene/10090:Slc6a7 ^@ http://purl.uniprot.org/uniprot/Q6PGE7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A7 subfamily.|||Brain specific sodium (and chloride)-dependent proline transporter. Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals.|||Synaptic cell membrane http://togogenome.org/gene/10090:Eno2 ^@ http://purl.uniprot.org/uniprot/D3Z6E4|||http://purl.uniprot.org/uniprot/P17183|||http://purl.uniprot.org/uniprot/Q545V3 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the enolase family.|||Cell membrane|||Cytoplasm|||During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells, and to the alpha/gamma heterodimer in nerve cells.|||Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity).|||Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific.|||Mg(2+) is required for catalysis and for stabilizing the dimer.|||Skeletal muscle (at protein level). The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons. http://togogenome.org/gene/10090:Lat2 ^@ http://purl.uniprot.org/uniprot/Q9JHL0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Hardly expressed in pro-B and pre-B cells. Moderately expressed in immature B-cells, mature B-cells and plasma cells. Highly expressed in transitional B-cells.|||Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2.|||Mice exhibit normal T-cell, B-cell and mast cell development and normal humoral response, but have hyperresponsive mast cells.|||Phosphorylated on tyrosines following cross-linking of BCR in B-cells, high affinity IgG receptor (FCGR1) in myeloid cells, or high affinity IgE receptor (FCER1) in mast cells; which induces the recruitment of GRB2.|||Strongly expressed in testis. Expressed in heart, spleen and lung. Present in B-cells and mast cells (at protein level).|||When phosphorylated, interacts with GRB2. May also interact with SOS1, GAB1 and CBL. http://togogenome.org/gene/10090:Ctxn2 ^@ http://purl.uniprot.org/uniprot/Q3URE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cortexin family.|||Membrane http://togogenome.org/gene/10090:Vmn1r91 ^@ http://purl.uniprot.org/uniprot/E9PZR7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5d37 ^@ http://purl.uniprot.org/uniprot/A2AVT5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lamp3 ^@ http://purl.uniprot.org/uniprot/Q7TST5|||http://purl.uniprot.org/uniprot/Q8BZW9 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LAMP family.|||Cell surface|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Endosome membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lysosomal membrane glycoprotein which plays a role in the unfolded protein response (UPR) that contributes to protein degradation and cell survival during proteasomal dysfunction. Plays a role in the process of fusion of the lysosome with the autophagosome, thereby modulating the autophagic process. Promotes hepatocellular lipogenesis through activation of the PI3K/Akt pathway. May also play a role in dendritic cell function and in adaptive immunity.|||Lysosome membrane|||Membrane|||Monomer. Interacts with FURIN. http://togogenome.org/gene/10090:Psmf1 ^@ http://purl.uniprot.org/uniprot/A0A1S6GWI1|||http://purl.uniprot.org/uniprot/A2AU35|||http://purl.uniprot.org/uniprot/Q8BHL8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the proteasome inhibitor PI31 family.|||Cytoplasm|||Endoplasmic reticulum|||Monomer and homodimer. Interacts with FBXO7 (By similarity).|||Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28 (By similarity).|||Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28. http://togogenome.org/gene/10090:Tent2 ^@ http://purl.uniprot.org/uniprot/Q91YI6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-B-like family. GLD2 subfamily.|||Cytoplasm|||Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail. In contrast to the canonical nuclear poly(A) RNA polymerase, it only adds poly(A) to selected cytoplasmic mRNAs. Does not play a role in replication-dependent histone mRNA degradation. Adds a single nucleotide to the 3' end of specific miRNAs, monoadenylation stabilizes and prolongs the activity of some but not all miRNAs.|||Expressed in oocytes from metaphase I to metaphase II during oocyte maturation.|||Interacts with CPEB1, CPEB2, CPSF1 and PABPC1 (PubMed:17927953). Interacts with QKI isoform QKI7; promoting recruitment to miRNA miR-122 and miR-122 stabilization (By similarity).|||Mice are normal and healthy. Poly-A tail elongation in oocytes is not affected and mice are fertile.|||Nucleus|||Ubiquitous. In brain, it is highly expressed in the cerebral cortex, cerebellum, hippocampus and olfactory bulb. http://togogenome.org/gene/10090:Slc16a9 ^@ http://purl.uniprot.org/uniprot/Q7TM99 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Extracellular pH-and Na(+)-sensitive low-affinity creatine transporter. Functions also as a pH-independent carnitine efflux transporter. http://togogenome.org/gene/10090:Tcf3 ^@ http://purl.uniprot.org/uniprot/P15806 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Expressed during the development of the nervous system.|||Facilitates ATOH7 binding to DNA at the consensus sequence 5'-CAGGTG-3', and positively regulates transcriptional activity.|||Forms a heterodimer with ATOH7; required for ATOH7 DNA-binding.|||Homodimer (PubMed:12196028). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (PubMed:15226298). Forms a heterodimer with TWIST1 and TWIST2 (PubMed:7589808, PubMed:23395635). Forms a heterodimer with NEUROD1; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element (PubMed:23395635, PubMed:18069799). Forms a heterodimer with TCF15; the heterodimer binds E-box element (PubMed:15226298, PubMed:23395635). Forms a heterodimer with MYOG; heterodimerization enhances MYOG DNA-binding and transcriptional activities (PubMed:12196028). Forms a heterodimer with ATOH8; repress transcription of TCF3 and TCF3-NEUROG3 dimer-induced transactivation of E box-dependent promoters (PubMed:23938248). Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 (PubMed:16407974). Interacts with NEUROD2 (PubMed:18214987). Interacts with EP300 (By similarity). Interacts with PTF1A, TGFB1I1 and UBE2I (PubMed:9409784, PubMed:11318877, PubMed:16291758). Interacts with BHLHA9 (By similarity). Interacts with ASB2; the interaction is mediated by SKP2 and targets TCF3 for Notch-induced proteasomal degradation (By similarity). Interacts with transcription factor ASCL5/AmeloD.|||Interacts with RALGAPA1 (PubMed:12200424). Interacts with FIGLA (By similarity).|||Mice are smaller than their wild-type littermates and fail to thrive 14 days after birth.|||Nucleus|||Phosphorylated following NGF stimulation.|||Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition (PubMed:15226298, PubMed:18214987). Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation (PubMed:18214987). Together with TCF15, required for the mesenchymal to epithelial transition (PubMed:11309385, PubMed:15226298). Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (PubMed:15226298, PubMed:18214987, PubMed:30426815). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (By similarity). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (PubMed:2181401).|||Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Nemp1 ^@ http://purl.uniprot.org/uniprot/Q6ZQE4|||http://purl.uniprot.org/uniprot/Q8K2N3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NEMP family.|||Homooligomer (By similarity). Interacts with RAN-GTP (PubMed:25946333). Interacts with EMD (By similarity).|||In the ovary, expression is strongest in primordial follicle oocytes and rapidly declines as oocytes mature and move from the cortex (at protein level).|||Mutants are viable and generally healthy although anemic (PubMed:32923640). Most females are sterile or severely subfertile while males are fertile (PubMed:32923640). Marked reduction in the number of primordial follicles, indicating a reduced ovarian reserve, and oocytes have reduced nuclear envelope stiffness (PubMed:32923640).|||Nucleus envelope|||Nucleus inner membrane|||Phosphorylated. Phosphorylation may regulate its interaction with RAN-GTP.|||The transmembrane domains are required and sufficient for its oligomerization.|||Together with EMD, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). Required for female fertility (PubMed:32923640). http://togogenome.org/gene/10090:Zap70 ^@ http://purl.uniprot.org/uniprot/P43404 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation at Tyr-492 in the activation loop.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.|||Cell membrane|||Composed of 2 N-terminal SH2 domains and a C-terminal kinase domain. The tandem SH2 domains bind to the doubly phosphorylated tyrosine-based activation motif (ITAM) of CD247/CD3Z and the non-canonical phosphorylated tyrosine-based activation motif (TAM) of RHOH (By similarity). The interdomain B located between the second SH2 and the kinase domain has been implicated in binding to other signaling molecules including CBL or VAV1. Thus, ZAP70 can also function as a scaffold by recruiting additional factors to the stimulated TCR complex (By similarity).|||Cytoplasm|||Interacts with CD247/CD3Z; this interaction docks ZAP70 at the stimulated TCR (By similarity). Interacts with NFAM1 (PubMed:15143214). Interacts with adapter protein SLA; this interaction negatively regulates T-cell receptor signaling (PubMed:10662792). Interacts with VAV1 (By similarity). Interacts with CBL; this interaction promotes ubiquitination, internalization and subsequent degradation of CD247/CD3Z (By similarity). Identified in a complex with CBL and UBE2L3 (By similarity). Interacts with SHB (By similarity). Interacts with adapter protein SLA2; this interaction negatively regulates T-cell receptor signaling (PubMed:11891219). Interacts with CBLB (PubMed:10646608). Interacts (via SH2 domains) with RHOH; this interaction regulates ZAP70 subcellular localization (PubMed:17028588). Interacts with DEF6 (PubMed:12648457). Interacts (ubiquitinated form) with OTUD7B and UBASH3B (PubMed:26903241).|||Isoform 1 and isoform 2 are expressed in thymus, spleen and lymph nodes.|||Isoform 2 is expressed in developing thymocytes from the CD44+CD25- stage up to mature T-cells. Isoform 1 is not expressed in thymocytes at the CD44+CD25- or CD44+CD25+ stages.|||Mice lack both CD4 and CD8 positive mature T-lymphocytes. Displays a complete block in B-Cell development at the pro-B cell stage in the absence of both SYK and ZAP70.|||Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Phosphorylation of Tyr-314 and Tyr-314 are essential for ZAP70 positive function on T-lymphocyte activation whereas Tyr-290 has a negative regulatory role. Within the C-terminal kinase domain, Tyr-491 and Tyr-492 are phosphorylated after TCR induction, Tyr-491 playing a negative regulatory role and Tyr-492 a positive. Tyr-492 is dephosphorylated by PTN22.|||Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).|||Ubiquitinated in response to T cell activation. Deubiquitinated by OTUD7B. http://togogenome.org/gene/10090:Colq ^@ http://purl.uniprot.org/uniprot/O35348 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Anchors the catalytic subunits of asymmetric AChE to the synaptic basal lamina.|||Belongs to the COLQ family.|||Homotrimer. Component of the asymmetric form of AChE, a disulfide-bonded oligomer composed of the collagenic subunits (Q) and a variable number of asymmetric catalytic subunits (T). The N-terminal of a collagenic subunit (Q) associates with the C-terminal of a catalytic subunit (T) (By similarity).|||Synapse|||The proline-rich attachment domain (PRAD) binds the AChE catalytic subunits.|||The triple-helical tail is stabilized by disulfide bonds at each end. http://togogenome.org/gene/10090:Crtac1 ^@ http://purl.uniprot.org/uniprot/Q8R555 ^@ Subcellular Location Annotation ^@ extracellular matrix http://togogenome.org/gene/10090:F13a1 ^@ http://purl.uniprot.org/uniprot/Q3V3W7|||http://purl.uniprot.org/uniprot/Q8BH61 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 1 Ca(2+) ion per subunit.|||Cytoplasm|||Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin.|||Secreted|||Tetramer of two A chains (F13A1) and two B (F13B) chains.|||The activation peptide is released by thrombin. http://togogenome.org/gene/10090:Bdkrb1 ^@ http://purl.uniprot.org/uniprot/Q0VBD7|||http://purl.uniprot.org/uniprot/Q61125 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Bradykinin receptor subfamily. BDKRB1 sub-subfamily.|||By lipopolysaccharide (LPS) in heart, liver and lung five hours after treatment.|||Cell membrane|||Expressed in heart, liver and lung.|||Membrane|||This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation. http://togogenome.org/gene/10090:Sytl2 ^@ http://purl.uniprot.org/uniprot/Q99N50 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Due to intron retention.|||Highly expressed in brain, lung, kidney, testis and in embryos after day 7. Detected at lower levels in skeletal muscle. Expressed in pancreatic alpha cells. Isoform 6 is highly expressed in brain, but not detectable in the other tissues tested. Isoform 1 is expressed abundantly in the stomach and is predominantly localized at the apical region of gastric-surface mucus cells. Isoform 11 is expressed in cytotoxic T-lymphocytes (CTL).|||Isoform 1 is highly susceptible to proteolytic degradation and is stabilized by the interaction with RAB27A.|||Isoform 11 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. Required for cytotoxic granule docking at the immunologic synapse. Isoform 1 may play a role in melanosome transport and vesicle trafficking. It controls melanosome distribution in the cell periphery and regulates melanocyte morphology. Isoform 1 acts as a positive mediator of mucus secretion by the surface mucus cells of the stomach. Mediates basal mucus secretion by gastric surface cells by promoting the proper granule biognesis and docking of mucus granules with the apical plasma membrane.|||Melanosome membrane|||Mice show a reduced number of mucus granules, a deficiency of granule docking with the apical plasma membrane in the gastric-surface mucus cells and reduction of mucus secretion by gastric primary cells.|||Monomer. Binds NRXN1. Binds RAB27A that has been activated by GTP-binding. Interacts with RAB27B.|||The C2 1 domain mediates localization to the cell membrane.|||The RabBD domain mediates interaction with RAB27A. http://togogenome.org/gene/10090:Bicc1 ^@ http://purl.uniprot.org/uniprot/G3X8S6|||http://purl.uniprot.org/uniprot/Q99MQ1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BicC family.|||Cytoplasm|||In the adult, predominantly expressed in heart and kidney. In 8 week old mice, expressed in growing primary oocytes and in the stromal cells of the theca.|||In the developing embryo, first detected at the rostral tip of the primitive streak, Hensen's node, at the late streak stage. At the late headfold stage, expression demarcates the layer of the node from which definitive endoderm and midline mesoderm arises. At 6-8 somite stage observed in the definitive endoderm. Strong expression is detected in the caudal intestinal portal. At 12-15 somite stage is still present in the hindgut, but transient expression is also seen in tissues of neural and mesodermal origins. At 13 dpc present around all sites of cartilage formation, such as cervical vertebral bodies, ribs and Merckel's cartilage. Additionally, expressed in the derivatives of the pleuroperitoneal membrane, the diaphragm and the pericardium, as well as the mesenchyme of the developing lung. Expressed in both the mesonephros and metanephros.|||Interacts (via KH domains) with ANKS6 (via SAM domain) in an RNA-dependent manner. Interacts with ANKS3 (PubMed:25671767).|||Putative RNA-binding protein. May be involved in regulating gene expression during embryonic development. http://togogenome.org/gene/10090:Htr6 ^@ http://purl.uniprot.org/uniprot/Q14AW8|||http://purl.uniprot.org/uniprot/Q9R1C8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with CDK5 (PubMed:25078650). Interacts with MTOR (PubMed:23027611). Interacts with RPTOR and NF1 (By similarity).|||Membrane|||This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that function as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (PubMed:25078650). Is an activator of TOR signaling (PubMed:23027611). http://togogenome.org/gene/10090:Gstm3 ^@ http://purl.uniprot.org/uniprot/P19639 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Slc26a2 ^@ http://purl.uniprot.org/uniprot/Q62273 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Cell membrane|||Distributed mainly in the thymus, testis and osteoblastic cells (PubMed:9370300). Highly expressed in the bone, cartilage, kidney and colon (PubMed:24302720).|||N-glycosylated.|||Sulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development (PubMed:24302720). Mediates electroneutral anion exchange of sulfate ions for oxalate ions, sulfate and oxalate ions for chloride and/or hydroxyl ions and chloride ions for bromide, iodide and nitrate ions (PubMed:20219950, PubMed:22190686, PubMed:24302720). The coupling of sulfate transport to both hydroxyl and chloride ions likely serves to ensure transport at both acidic pH when most sulfate uptake is mediated by sulfate-hydroxide exchange and alkaline pH when most sulfate uptake is mediated by sulfate-chloride exchange (PubMed:22190686). Essential for chondrocyte proliferation, differentiation and cell size expansion (PubMed:24302720). http://togogenome.org/gene/10090:Scgb1b30 ^@ http://purl.uniprot.org/uniprot/A2BH64 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Abcg2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B6|||http://purl.uniprot.org/uniprot/Q7TMS5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.|||Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:10485464, PubMed:12477054, PubMed:12429862, PubMed:17145775, PubMed:30042379). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:12429862, PubMed:15044468). Also mediates the efflux of sphingosine-1-P from cells (By similarity). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (By similarity). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (PubMed:30042379). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (By similarity). Mediates the secretion of the riboflavin and biotin vitamins into milk (PubMed:17145775). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (PubMed:12429862). Plays an important role in the exclusion of xenobiotics from the brain (PubMed:10485464). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:12477054). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (PubMed:12429862). May play a role in early stem cell self-renewal by blocking differentiation (Probable).|||Cell membrane|||Highly expressed in kidney. Lower expression in liver, colon, heart, spleen, and placenta (PubMed:11036110). Expressed in mammary gland (PubMed:17145775). Expressed in intestinal villi and renal proximal tubules, hepatic bile canalicular membranes, and placental labyrinth cells (at protein level) (PubMed:12429862).|||Homodimer; disulfide-linked. The minimal functional unit is a homodimer, but the major oligomeric form in plasma membrane is a homotetramer with possibility of higher order oligomerization up to homododecamers.|||Membrane|||Mice lacking Abcg2 are born at the expected Mendelian ratio and do not display overt phenotype (PubMed:12429862). However, under specific housing conditions, they show phototoxic skin lesions induced by pheophorbide a, a porphyrin catabolite of chlorophyll found in their diet, that accumulates in mice plasma (PubMed:12429862). They also accumulate a red substance in their bile and display protoporphyria with an accumulation of protoporphyrin IX (PPIX) in erythrocytes (PubMed:12429862). Mice lacking Abcg2 present decreased elimination of some uremic toxins like indoxyl sulfate leading to their accumulation in plasma (PubMed:30042379). They also show reduced survival rate upon adenine-induced chronic kidney disease (PubMed:30042379).|||Mitochondrion membrane|||N-glycosylated. Glycosylation-deficient ABCG2 is normally expressed and functional.|||Phosphorylated. Phosphorylation may regulate the localization to the plasma membrane, the homooligomerization and therefore, the activity of the transporter.|||Specifically inhibited by the fungal toxin fumitremorgin C and Ko143.|||The extracellular loop 3 (ECL3) is involved in binding porphyrins and transfer them to other carriers, probably albumin.|||Up-regulated upon hypoxia. http://togogenome.org/gene/10090:Zbtb18 ^@ http://purl.uniprot.org/uniprot/Q9WUK6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family. ZBTB18 subfamily.|||Death shortly after birth. Brain of mutant mice display dysplasia of the neocortex and of the hippocampus, reduction of the number of mature cortical neurons and defects of laminar organization. In the cortex, an impaired cell-division patterning during the late embryonic stage and an enhancement of apoptosis of the postmitotic neurons are observed.|||In the developing brain, expression is detected at embryonic day (E) 10 in the neuroepithelium, and subsequently in the ventricular zones of the cerebral cortex in the 12 dpc embryo. Strong expression is observed in the preplate in the cerebral cortex from this stage onward. High levels of expression continue to be detected in the cortical plate and subventricular zone of the neocortex, hippocampus, and parts of the amygdala, but not in the thalamus or striatum. In the developing cerebral cortex, it is expressed both in postmitotic glutamatergic projection neurons and in their progenitor cells, but not in GABAergic interneurons. Also expressed in the adult neocortex, hippocampus, parts of the amygdala and granule cells in the cerebellum.|||Interacts with DNMT3A.|||Nucleus|||Transcriptional repressor that plays a role in various developmental processes such as myogenesis and brain development. Specifically binds the consensus DNA sequence 5'-[AC]ACATCTG[GT][AC]-3' which contains the E box core, and acts by recruiting chromatin remodeling multiprotein complexes. Plays a key role in myogenesis by directly repressing the expression of ID2 and ID3, 2 inhibitors of skeletal myogenesis. Also involved in controlling cell division of progenitor cells and regulating the survival of postmitotic cortical neurons. May also play a role in the organization of chromosomes in the nucleus. http://togogenome.org/gene/10090:Sh2d5 ^@ http://purl.uniprot.org/uniprot/Q8JZW5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in brain, particularly in Purkinjie cells in the cerebellum and the cornu ammonis of the hippocampus.|||Interacts with BCR.|||May be involved in synaptic plasticity regulation through the control of Rac-GTP levels.|||Postsynaptic density http://togogenome.org/gene/10090:Atoh1 ^@ http://purl.uniprot.org/uniprot/P48985 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Developing nervous system, and in adult epithelial cells of the gastrointestinal tract.|||Efficient DNA binding requires dimerization with another bHLH protein.|||First detected in the cranial ganglions and the dorsal part of the central nervous system on 9.5 dpc (PubMed:7721778). From 10.5 dpc onward, prominently expressed in the dorsal part of the central nervous system but becomes restricted to the external granular layer of the cerebellum by 18 dpc and is undetectable in the adult nervous system (PubMed:7721778). Expressed in the cochlear nucleus at 15.5 dpc (PubMed:17977745).|||Nucleus|||Transcriptional regulator. Activates E box-dependent transcription in collaboration with TCF3/E47, but the activity is completely antagonized by the negative regulator of neurogenesis HES1. Plays a role in the differentiation of subsets of neural cells by activating E box-dependent transcription. http://togogenome.org/gene/10090:Atp6v0e ^@ http://purl.uniprot.org/uniprot/Q9CQD8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase e1/e2 subunit family.|||Membrane|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). http://togogenome.org/gene/10090:H1f0 ^@ http://purl.uniprot.org/uniprot/P10922 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ ADP-ribosylated on Ser-104 in response to DNA damage.|||Belongs to the histone H1/H5 family.|||Chromosome|||Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. The histones H1.0 are found in cells that are in terminal stages of differentiation or that have low rates of cell division.|||Nucleus http://togogenome.org/gene/10090:Vmn1r85 ^@ http://purl.uniprot.org/uniprot/Q8VIB8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppp1r16a ^@ http://purl.uniprot.org/uniprot/Q923M0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds PP1.|||Cell membrane|||Highly expressed in testis, followed by liver, heart, brain and lung.|||Inhibits protein phosphatase 1 activity toward phosphorylase, myosin light chain and myosin substrates. http://togogenome.org/gene/10090:Ces1f ^@ http://purl.uniprot.org/uniprot/Q91WU0 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Endoplasmic reticulum|||Expressed in liver, white and brown adipose tissue, kidney, intestine, adrenal, heart and ovary. Not detected in muscle, lung, testis, brain and spleen.|||Induced by fasting and repressed by refeeding.|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes retinyl esters (By similarity). Hydrolyzes p-nitrophenyl butyrate (PNPB), triacylglycerol and monoacylglycerol. Shows higher activity against PNPB, a short-chain fatty acid ester, than against triolein, a long-chain fatty acid ester. Shows no detectable activity against diacylglycerol, cholesterol ester or phospholipids. May play a role in adipocyte lipolysis.|||Lipid droplet|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Microsome|||cytosol http://togogenome.org/gene/10090:Cdc42se2 ^@ http://purl.uniprot.org/uniprot/Q8BGH7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDC42SE/SPEC family.|||Cell membrane|||Detected in spleen, thymus and lung (at protein level).|||Interacts with CDC42 (in GTP-bound form). Interacts weakly with RAC1 and not at all with RHOA (By similarity).|||Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages (By similarity).|||The CRIB domain mediates interaction with CDC42.|||cytoskeleton|||phagocytic cup http://togogenome.org/gene/10090:Usp18 ^@ http://purl.uniprot.org/uniprot/Q9WTV6 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the peptidase C19 family.|||Interacts with STAT2; the interaction is direct. Interacts with IFNAR2; indirectly via STAT2, it negatively regulates the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and inhibits type I interferon signaling. Interacts with STING1. Interacts with USP20.|||Interferon-induced ISG15-specific protease that plays a crucial role for maintaining a proper balance of ISG15-conjugated proteins in cells (PubMed:11788588). Regulates protein ISGylation by efficiently cleaving ISG15 conjugates linked via isopeptide bonds. Regulates T-cell activation and T-helper 17 (Th17) cell differentiation by deubiquitinating TAK1, likely to keep TAK1-TAB complexes in steady conditions. In turn, restricts activation of NF-kappa-B, NFAT, and JNK as well as expression of IL2 in T-cells after TCR activation. Acts as a molecular adapter with USP20 to promote innate antiviral response through deubiquitinating STING1. Involved also in the negative regulation of the inflammatory response triggered by type I interferon. Upon recruitment by STAT2 to the type I interferon receptor subunit IFNAR2 interferes with the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative regulator of the type I interferon signaling pathway.|||USP18-deletion mice display increased levels of intracellular ISG15 conjugates. http://togogenome.org/gene/10090:Ecpas ^@ http://purl.uniprot.org/uniprot/Q6PDI5 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins. May couple the proteasome to different compartments including endosome, endoplasmic reticulum and centrosome. May play a role in ERAD and other enhanced proteolysis (By similarity). Promotes proteasome dissociation under oxidative stress (PubMed:26802743).|||Belongs to the ECM29 family.|||Cytoplasmic vesicle|||Deficient mice are viable, fertile, and do not show any histological abnormalities. Under stressed condition, 26S proteasome dissociates in wild-type cells, but not in cells from deficient mice.|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Endosome|||Intron retention.|||Non-stoichiometric component of the proteasome; associates with the 26S proteasome. Interacts (via N-terminus) with VPS11, VPS26A, VPS36, RAB11FIP4 and RABEP1. Interacts (via C-terminus) with DCTN1, DCTN2, KIF5B, MYH7, MYH10, MYO10 and ARF6.|||Nucleus|||Widely expressed (at protein level).|||centrosome|||multivesicular body http://togogenome.org/gene/10090:B3galt6 ^@ http://purl.uniprot.org/uniprot/Q91Z92 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-galactosyltransferase that transfers galactose from UDP-galactose to substrates with a terminal beta-linked galactose residue. Has a preference for galactose-beta-1,4-xylose that is found in the linker region of glycosaminoglycans, such as heparan sulfate and chondroitin sulfate. Has no activity towards substrates with terminal glucosamine or galactosamine residues.|||Golgi stack membrane http://togogenome.org/gene/10090:Oprk1 ^@ http://purl.uniprot.org/uniprot/A0A5F8MP90|||http://purl.uniprot.org/uniprot/P33534|||http://purl.uniprot.org/uniprot/Q14AL5|||http://purl.uniprot.org/uniprot/Q3UVW8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in brain (at protein level). Brain (neocortex, hippocampus, amygdala, medial habenula, hypothalamus, locus ceruleus, and parabrachial nucleus).|||G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.|||Interacts with NHERF1. Interacts with GABARAPL1 (By similarity).|||Interacts with NHERF1. Interacts with GABARAPL1.|||Membrane|||Mice are born at the expected Mendelian rate and show no obvious phenotype. Mutant mice do not display analgesia after treatment with the synthetic agonist U-50,488H. Unlike wild-type mice, they do not show reduced locomotion and increased salivation in response to the synthetic agonist U-50,488H. http://togogenome.org/gene/10090:Vmn1r13 ^@ http://purl.uniprot.org/uniprot/G5E8I3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r101 ^@ http://purl.uniprot.org/uniprot/E9Q365 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gal3st2 ^@ http://purl.uniprot.org/uniprot/A2RTS9|||http://purl.uniprot.org/uniprot/Q3UN22 ^@ Similarity ^@ Belongs to the galactose-3-O-sulfotransferase family. http://togogenome.org/gene/10090:Prpf4 ^@ http://purl.uniprot.org/uniprot/Q059T9|||http://purl.uniprot.org/uniprot/Q9DAW6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the precatalytic spliceosome (spliceosome B complex) (By similarity). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (By similarity). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (By similarity). Interacts directly with PRPF18, PPIH and PRPF3 (By similarity). Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA (By similarity). Interacts with ERCC6 (By similarity).|||Nucleus|||Nucleus speckle|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). http://togogenome.org/gene/10090:Bdnf ^@ http://purl.uniprot.org/uniprot/P21237|||http://purl.uniprot.org/uniprot/Q541P3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NGF-beta family.|||Contrary to mature BDNF, the propeptide is N-glycosylated and glycosulfated.|||During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS.|||Expressed in the dorsal root ganglion and the spinal cord (at protein level) (PubMed:28111162). Detected in brain, especially in brain cortex, hippocampus, midbrain and cerebellum (PubMed:2369898, PubMed:8139657).|||Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain (PubMed:23785138). Expressed at higher levels during the dark period and at lower levels during the light period (PubMed:23785138). Up-regulated after sciatic nerve injury (PubMed:28111162).|||Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:27457814). Activates signaling cascades via the heterodimeric receptor formed by NGFR and SORCS2 (PubMed:24908487, PubMed:29909994). Signaling via NGFR and SORCS2 plays a role in synaptic plasticity and long-term depression (LTD) (PubMed:27457814). Binding to NGFR and SORCS2 promotes neuronal apoptosis (PubMed:24908487). Promotes neuronal growth cone collapse (PubMed:24908487, PubMed:27457814).|||Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:27457814). During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability (PubMed:8139657, PubMed:15486301, PubMed:17023662, PubMed:27457814, PubMed:29909994).|||Mature BDNF is produced by proteolytic removal of the propeptide, catalyzed by a FURIN family member. In addition, the precursor form is proteolytically cleaved within the propeptide, but this is not an obligatory intermediate for the production of mature BDNF (By similarity). Can be converted into mature BDNF by plasmin (PLG) (PubMed:15486301).|||Monomers and homodimers (PubMed:7957235). Binds to NTRK2/TRKB (By similarity). Can form heterodimers with other neurotrophin family members, such as NTF3 and NTF4 (in vitro), but the physiological relevance of this is not clear (By similarity). BDNF precursor form: interacts with the heterodimer formed by NGFR and SORCS2. Mature BDNF has much lower affinity for the heterodimer formed by NGFR and SORCS2 (PubMed:24908487).|||Monomers and homodimers. Binds to NTRK2/TRKB.|||Mutant mice are smaller than wild-type littermates, and most die during the second week after birth. They exhibit impaired motor coordination and balance, head bobbing and tilting, and spinning during perionds of hyperactivity. Mutant mice display a strongly reduced number of neurons in the dorsal root ganglion, trigeminal ganglion, mesencephalic trigeminal nucleus, vestibular ganglion and nodose ganglion. Cell death of vestibular ganglion neurons is strongly increased 14 days after birth. The number of facial motor neurons and sympathetic superior cervical ganglion neurons are not decreased. Mutant mice display defects in the innervation of the inner ear, but respond to auditory stimuli. Tne inner ear from mutant mice has fewer nerve fibers that enter the sacculus, utricle and ampulla of the semicircular ducts, and axons fail to contact their target cells and terminate in the connective tissue adjacent to the sensory epithelia of the sacculus.|||Secreted http://togogenome.org/gene/10090:Atf4 ^@ http://purl.uniprot.org/uniprot/Q06507 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family.|||Binds DNA as a homodimer and as a heterodimer (PubMed:23624402). Heterodimer; heterodimerizes with CEBPB (PubMed:11018027). Heterodimer; heterodimerizes with DDIT3/CHOP (PubMed:23624402). Interacts with CEP290 (via an N-terminal region) (By similarity). Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3 (By similarity). Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C-termini) (By similarity). Forms a heterodimer with TXLNG in osteoblasts (PubMed:15911876). Interacts (via its DNA binding domain) with FOXO1 (C-terminal half); the interaction occurs in osteoblasts and regulates glucose homeostasis through suppression of beta-cell proliferation and a decrease in insulin production (PubMed:22298775). Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (PubMed:16751105). Interacts with ABRAXAS2 (PubMed:22974638). Interacts with TRIB3, inhibiting the transactivation activity of ATF4 (PubMed:17369260). Interacts with DISC1; which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). Interacts with EP300/p300; EP300/p300 stabilizes ATF4 and increases its transcriptional activity independently of its catalytic activity by preventing its ubiquitination (By similarity).|||Cell membrane|||Cytoplasm|||During embryonic development, expressed at high levels in anterior epithelial lens cells at 14.5 dpc (PubMed:10885750). At 16.5 dpc, expressed in osteoblasts surrounding newly formed trabecular bone (PubMed:19232401). At postnatal day 2, detected in most osteoblasts and lining cells (PubMed:19232401). By postnatal week 4, is detected in fewer osteoblasts, but remains present in lining cells (at protein level) (PubMed:19232401).|||Hydroxylated by PHD3, leading to decreased protein stability.|||Mice were born at a much lower rate than predicted by the Mendelian ratio (PubMed:10096021, PubMed:10885750). Homozygous pups generally die during the first hour after birth, although excess mortality occurrs throughout the first 3 weeks of life (PubMed:10096021, PubMed:11806972). Embryos are severely anemic during fetal development, due to an impairment in definitive hematopoiesis (PubMed:11806972). Surviving mice display defects in embryonic lens formation leading to severe microphthalmia in adults (PubMed:10096021, PubMed:10885750). Embryos show delayed bone formation and surviving mice display low bone mass throughout postnatal life (PubMed:15109498). Surviving null mice exhibit an increase in serum insulin levels and low blood glucose levels (PubMed:22298775). There is a decrease in total fat content, gonadal fat, lean mass and body weight (PubMed:22298775). Serum levels of osteocalcin/BGLAP are decreased (PubMed:22298775). PBK/AKT1-mediated phosphorylation of FOXO1 at 'Ser-258' is increased with a subsequent decrease of FOXO1-mediated transcriptional activity (PubMed:22298775).|||Nucleus|||Nucleus speckle|||Phosphorylation at Ser-251 by RPS6KA3/RSK2 in osteoblasts enhances transactivation activity and promotes osteoblast differentiation (PubMed:15109498). Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination (PubMed:23663782). Phosphorylation is promoted by mTORC1 (PubMed:23663782). Phosphorylation at Ser-214 by CK2 decreases its stability (By similarity). Phosphorylated by NEK6 (By similarity).|||Regulated at the translational level in response to various stress such as endoplasmic reticulum stress, amino acid starvation or oxidative stress (PubMed:11106749, PubMed:12667446, PubMed:15277680, PubMed:21159964). In the absence of stress, ribosomes re-initiate translation at an inhibitory open reading frame (uORF) upstream of the ATF4 transcript, which precludes AFT4 translation (PubMed:11106749, PubMed:15277680). In response to stress and subsequent EIF2S1/eIF-2-alpha phosphorylation, ribosomes bypass the inhibitory uORF and re-initiate translation at the AFT4 coding sequence (PubMed:15277680). Expressed in a circadian manner in the midbrain with an increased expression seen during the dark phase (at protein level) (PubMed:21768648, PubMed:22572884). Expressed in a circadian manner also in the suprachiasmatic nucleus (SCN) of the brain, cerebral cortex, kidney and small intestine (PubMed:21768648, PubMed:22572884).|||The BetaTrCP degron motif promotes binding to BTRC when phosphorylated.|||Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:8506317, PubMed:11106749, PubMed:12667446, PubMed:23624402). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (PubMed:8506317, PubMed:23624402). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:11106749, PubMed:12667446). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:11106749, PubMed:12667446). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (PubMed:12667446). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (By similarity). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:15775988, PubMed:21159964). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (By similarity). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (PubMed:23624402). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988, PubMed:17369260, PubMed:21159964). May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (By similarity). In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (PubMed:10096021, PubMed:10885750, PubMed:11806972, PubMed:12925279, PubMed:15109498, PubMed:22298775). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (PubMed:22298775). Activates transcription of SIRT4 (PubMed:23663782). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (PubMed:21768648, PubMed:22572884). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (PubMed:21768648, PubMed:22572884). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (PubMed:12925279). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471).|||Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4 (PubMed:23663782). Interaction with EP300/p300 inhibits ubiquitination by SCF(BTRC) (By similarity).|||Ubiquitously expressed in adults.|||centrosome http://togogenome.org/gene/10090:Nhlh1 ^@ http://purl.uniprot.org/uniprot/Q02576 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||May serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.|||Nucleus http://togogenome.org/gene/10090:Fdps ^@ http://purl.uniprot.org/uniprot/Q4FJN9|||http://purl.uniprot.org/uniprot/Q920E5 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FPP/GGPP synthase family.|||Binds 2 Mg(2+) ions per subunit.|||Cytoplasm|||Homodimer. Interacts with RSAD2 (By similarity).|||Inactivated by interferon-induced RSAD2. This inactivation may result of disruption of lipid rafts at the plasma membrane, and thus have an antiviral effect since many enveloped viruses need lipid rafts to bud efficiently out of the cell (By similarity).|||Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate (By similarity). http://togogenome.org/gene/10090:Zmynd15 ^@ http://purl.uniprot.org/uniprot/Q8C0R7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor through interaction with histone deacetylases (HDACs). May regulate haploid genes important for spermiogenesis.|||At the mRNA level, first detected in early pachytene spermatocytes. At the protein level, first detected in step 2 round spermatids. Expression continuously increases thereafter and peaks in spermatids at steps 7-9 (at protein level). Levels start to decrease after step 9 and in step 9-11 elongating spermatids (at protein level).|||Cytoplasm|||Interacts with HDAC1, HDAC3, HDAC6 and, to a lesser extent, with HDAC7.|||Nucleus|||Since CXCL16 and ZMYND15 genes overlap in their 5'UTRs, CXCL16 knockout also disrupts the ZMYND15 gene. The double knockout mice display severe depletion of late spermatids and are thus infertile. This phenotype is probably due to ZMYND15, rather than CXCL16, deficiency.|||Testis-specific. Expressed in pachytene spermatocytes and all developing spermatids, but not in Sertoli, nor Leydig cells (at protein level). http://togogenome.org/gene/10090:Agpat4 ^@ http://purl.uniprot.org/uniprot/Q8K4X7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:15367102). Exhibits high acyl-CoA specificity for polyunsaturated fatty acyl-CoA, especially docosahexaenoyl-CoA (22:6-CoA, DHA-CoA) (PubMed:24333445).|||Endoplasmic reticulum membrane|||Expressed at a high levels in the brain, at intermediate or low levels in skeletal muscles, gut, kidney, spleen and lung (PubMed:15367102, PubMed:24333445). Barely detectable in heart and liver (PubMed:15367102).|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate. http://togogenome.org/gene/10090:Sidt1 ^@ http://purl.uniprot.org/uniprot/E9Q247|||http://purl.uniprot.org/uniprot/Q6AXF6|||http://purl.uniprot.org/uniprot/Q6Q3F6|||http://purl.uniprot.org/uniprot/Q8BZK2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SID1 family.|||In vitro binds long double-stranded RNA (dsRNA) (500 and 700 base pairs), but not dsRNA shorter than 300 bp (PubMed:26067272). Not involved in RNA autophagy, a process in which RNA is directly imported into lysosomes in an ATP-dependent manner, and degraded (PubMed:27046251).|||Membrane http://togogenome.org/gene/10090:Ube2cbp ^@ http://purl.uniprot.org/uniprot/Q8BX13 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.|||Interacts with UBE2C/UbcH10 (E2 ubiquitin-conjugating enzyme).|||The C-terminal half (AA 167-368) is able to bind cyclin-B and shows a self-ubiquitination activity (mono-, poly, or multi-ubiquitination) in a HECT-like sequence dependent manner.|||Ubiquitinated by UBCH10 (E2 ubiquitin-conjugating enzyme). http://togogenome.org/gene/10090:Lrp2 ^@ http://purl.uniprot.org/uniprot/A2ARV4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A fraction undergoes proteolytic cleavage of the extracellular domain at the cell membrane to generate a cytoplasmic tail fragment. This is internalized into the early endosome from where it trafficks in an LDLRAP1/ARH-dependent manner to the endocytic recycling compartment (ERC). In the ERC, it is further cleaved by gamma-secretase to release a fragment which translocates to the nucleus and mediates transcriptional repression.|||Apical cell membrane|||Belongs to the LDLR family.|||Binds plasminogen, extracellular matrix components, plasminogen activator-plasminogen activator inhibitor type I complex, apolipoprotein E-enriched beta-VLDL, lipoprotein lipase, lactoferrin, CLU/clusterin and calcium. Forms a multimeric complex together with LRPAP1 (By similarity). Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats) (By similarity). Interacts with LRP2BP. Interacts (via NPXY motif) with DAB2; the interaction is not affected by tyrosine phosphorylation of the NPXY motif (PubMed:11247302). Interacts with MB (By similarity). Interacts with BMP4 (PubMed:15623804). Interacts with the Sonic hedgehog protein N-product which is the active product of SHH (PubMed:11964399). Interacts with CST3 in a calcium-dependent manner (By similarity). Interacts with the vitamin-D binding protein GC/DBP (PubMed:10052453). Interacts with sex hormone-binding protein SHBG (By similarity). Interacts with angiotensin-2 (PubMed:15467006). Also interacts with angiotensin 1-7 (PubMed:16380466). Interacts with APOM (PubMed:16099815). Interacts with selenoprotein SEPP1 (PubMed:18174160). Interacts with LEP (By similarity). Interacts with ALB (By similarity). Interacts with the antiapoptotic protein BIRC5/survivin (By similarity). Interacts with matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity). In neurons, forms a trimeric complex with APP and APPB1/FE65 (PubMed:20637285). Interacts with LDLRAP1/ARH; mediates trafficking of LRP2 to the endocytic recycling compartment (By similarity). Does not interact with beta-amyloid protein 40 alone but interacts with the complex composed of beta-amyloid protein 40 and CLU/APOJ (By similarity). Interacts with MDK (PubMed:10772929).|||Down-regulated in the kidney by cannabinoids, such as endocannabinoid anandamide and synthetic cannabinoid HU-210.|||Endosome lumen|||In the developing optic nerve, more strongly expressed at 14.5 dpc and 16.5 dpc than at 18.5 dpc (at protein level) (PubMed:22354480). In the embryo, expression is detected from 7.5 dpc on the apical side of the developing neural plate and persists throughout later stages of development (PubMed:22340494). After neural tube closure at 9.5 dpc, becomes progressively restricted to the midline region (PubMed:22340494). During the estrus cycle, expression is highest in metestrus II and diestrus (PubMed:16143106).|||In the inner ear, strongly expressed in the marginal cells of the stria vascularis (at protein level) (PubMed:17846082). In the female reproductive tract, expressed on the luminal side of the uterine epithelium (at protein level) (PubMed:16143106). In the adult brain, expressed in ependymal cells of the lateral ventricles where expression is restricted to the ependyma that faces the stem cell niche (at protein level) (PubMed:20460439). Expressed in neurons throughout the brain including in the hippocampus, limbic cortices and cerebellum (at protein level) (PubMed:20637285). In the developing optic nerve, expressed exclusively in astrocytes at 14.5 dpc, 16.5 dpc and 18.5 dpc (at protein level) (PubMed:22354480).|||Multiligand endocytic receptor. Acts together with CUBN to mediate endocytosis of high-density lipoproteins (PubMed:10766831). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (PubMed:22841573). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight (PubMed:24825475). Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells (PubMed:17462596). Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP (PubMed:10052453). Mediates renal uptake of metallothionein-bound heavy metals (By similarity). Together with CUBN, mediates renal reabsorption of myoglobin (By similarity). Mediates renal uptake and subsequent lysosomal degradation of APOM (By similarity). Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1 (PubMed:18174160). Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (PubMed:28659595). Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH (By similarity). Also mediates ShhN transcytosis (By similarity). In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon (PubMed:15623804). Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH (PubMed:22340494). During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure (PubMed:24639464). In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed (PubMed:20460439). In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid (By similarity). Involved in neurite branching (PubMed:20637285). During optic nerve development, required for SHH-mediated migration and proliferation of oligodendrocyte precursor cells (PubMed:22354480). Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent (PubMed:26439398). Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG (PubMed:16143106). Mediates endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis of angiotensin 1-7 (By similarity). Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation (By similarity). Required for embryonic heart development (PubMed:26822476). Required for normal hearing, possibly through interaction with estrogen in the inner ear (PubMed:17846082).|||N-glycosylation is required for ligand binding. Contains core-fucosylated N-glycans in kidney proximal convoluted tubules (PCTs) and hybrid-type N-glycans in proximal straight tubules (PSTs). Interacts with ligands in a glycoform-dependent manner. Retinol-binding protein and the vitamin D carrier GC/DBP are endocytosed primarily by PCTs, albumin is endocytosed equally by PCTs and PSTs, and the aminoglycoside kanamycin is endocytosed primarily by PSTs.|||Severe facial dysgenesis and impaired forebrain development around mid-gestation, absence of Shh expression and decreased cell proliferation in the ventral neural tube, and aberrant expression of morphogens Fgf8 and Bmp4 (PubMed:15623804). Reduced expression of homeobox protein Six3 at 8.0 dpc in the prospective forebrain and impaired Shh expression at the ventral midline with resulting midline formation defects and holoprosencephaly (PubMed:22340494). At 9.5 dpc, loss of Shh in the ventral anterior diencephalon and increased Bmp4 expression in the dorsal forebrain (PubMed:22340494). Increased Bmp4 expression and impaired proliferation of neural precursor cells in the subependymal zone of the brain which results in decreased numbers of neuroblasts reaching the olfactory bulb (PubMed:20460439). Compound heterozygotes display enlarged and exophthalmic eyes with thinning of the retina (PubMed:26439398). Severe cardiovascular abnormalities including aortic arch anomalies, persistent truncus arteriosus with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve, marked thinning of the ventricular myocardium, and abnormal positioning of the neural crest cells and second heart field (PubMed:26822476). Impaired endocytosis of folate bound to the folate receptor FOLR1, reduced folate levels in embryos and impaired closure of the rostral neural tube (PubMed:24639464). High lethality at and after birth with survivors showing profound hearing loss, elevated lipofuscin granule levels and irregular apical surfaces in marginal cells of the stria vascularis, complete loss of potassium ion channel KCQN1 in basal and midbasal cochlear turns, and reduced estrogen uptake in the stria vascularis (PubMed:17846082). Survivors also display severe vitamin D deficiency and bone formation defects (PubMed:10052453). Failure of the vaginal cavity to open after birth in females and impaired testis descent in males with the left testis poorly developed and severely retarded in size (PubMed:16143106). Conditional knockout in the kidney results in reduced expression of CUBN in kidney cells and little or no uptake of myoglobin (PubMed:12724130). It also results in reduced uptake of Cst3 by kidney proximal tubule cells (PubMed:17462596). In addition, it causes pronounced urinary excretion of Apom, Birc5/survivin, and Mmp2 together with Timp1 (PubMed:16099815, PubMed:23825075, PubMed:28659595).|||The cytoplasmic domain is required for sorting to the apical cell membrane.|||Two overlapping PxLPxI/L motifs mediate interaction with ankyrin repeats of ANKRA2.|||axon|||coated pit|||dendrite http://togogenome.org/gene/10090:Tmem190 ^@ http://purl.uniprot.org/uniprot/Q9D2E9 ^@ Disruption Phenotype|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in testis and in a mixture of spermatogenic cells at various stages (testicular germ cells). Not detected in heart, brain, spleen, lung, liver, skeletal muscle and kidney.|||Membrane|||Mice are normal with no alterations in fertility, body size and behavior. http://togogenome.org/gene/10090:Bak1 ^@ http://purl.uniprot.org/uniprot/O08734 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with gamma-herpesvirus 68 protein vBCL2.|||Belongs to the Bcl-2 family.|||Homodimer. Formation of the homodimer is zinc-dependent. Forms heterodimers with BCL2 and BCL2L1 isoform Bcl-X(L). Forms heterooligomers with BAX (By similarity). Interacts with BCL2A1 (PubMed:18462686). Interacts withRTL10/BOP (PubMed:18462686). Interacts with VDAC1 (By similarity). Interacts with GIMAP3/IAN4 and GIMAP5/IAN5 (PubMed:16509771).|||In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2.|||Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.|||Mitochondrion outer membrane|||Widely expressed. http://togogenome.org/gene/10090:Mctp2 ^@ http://purl.uniprot.org/uniprot/Q5RJH2 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MCTP family.|||Binds Ca(2+) via the C2 domains in absence of phospholipids.|||Expressed at high levels in the developing heart, with high levels at 9.5 dpc that progressively decrease until 11.5 dpc.|||Membrane|||Might play a role in the development of cardiac outflow tract. http://togogenome.org/gene/10090:Apol9a ^@ http://purl.uniprot.org/uniprot/Q8VDU3 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Tas2r103 ^@ http://purl.uniprot.org/uniprot/Q9JKA3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in 15% taste bud cells in circumvallate and foliate papillae but only in 2% in fungiform papillae.|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Fgf14 ^@ http://purl.uniprot.org/uniprot/A0A0R4J063|||http://purl.uniprot.org/uniprot/O89096|||http://purl.uniprot.org/uniprot/P70379 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Brain and testis; widely distributed in the developing nervous system. In adult, high levels in the granular layer of the cerebellum, less in hippocampus and olfactory bulb.|||Interacts with SCN8A.|||Nucleus|||Probably involved in nervous system development and function. http://togogenome.org/gene/10090:Pdrg1 ^@ http://purl.uniprot.org/uniprot/P59048|||http://purl.uniprot.org/uniprot/Q3UKN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prefoldin subunit beta family.|||Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92.|||Cytoplasm|||May play a role in chaperone-mediated protein folding. http://togogenome.org/gene/10090:Ces2c ^@ http://purl.uniprot.org/uniprot/Q91WG0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Detected in liver (at protein level).|||Endoplasmic reticulum|||Hydrolase with high activity towards palmitoylcarnitine. Is also active with p-nitrophenylacetate and alpha-naphthylacetate. May also hydrolyze retinyl esters (By similarity).|||Microsome|||Up-regulated in liver by di-(2-ethylhexyl)phtalate (DEHP). http://togogenome.org/gene/10090:Ppil6 ^@ http://purl.uniprot.org/uniprot/Q9D6D8 ^@ Caution|||Function|||Similarity ^@ Belongs to the cyclophilin-type PPIase family.|||Despite the fact that it belongs to the cyclophilin-type PPIase family, it has probably no peptidyl-prolyl cis-trans isomerase activity.|||Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity. http://togogenome.org/gene/10090:Bmpr1a ^@ http://purl.uniprot.org/uniprot/P36895|||http://purl.uniprot.org/uniprot/Q53Z43 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Cell surface|||Glycosylated.|||Interacts with low affinity with GDF5; positively regulates chondrocyte differentiation (By similarity). Interacts with BMP4 (By similarity). Interacts with SCUBE3 (By similarity). Interacts with TSC22D1/TSC-22 (By similarity). Interacts with BMP2; the interaction may induce HAMP expression (PubMed:31800957). Interacts with BMP6 (PubMed:31800957). Interacts with heterodimers composed of BMP2 and BMP6 in vitro; the interaction may induce HAMP expression (PubMed:31800957).|||Membrane|||On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction (PubMed:24098149). Mediates induction of adipogenesis by GDF6 (PubMed:23527555). May promote the expression of HAMP, potentially via its interaction with BMP2 (PubMed:31800957).|||Widely expressed. http://togogenome.org/gene/10090:Vmn1r73 ^@ http://purl.uniprot.org/uniprot/Q8R293 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prkcb ^@ http://purl.uniprot.org/uniprot/P68404 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.|||Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity).|||Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) (By similarity).|||Cytoplasm|||Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By similarity).|||Membrane|||Mice develop an immunodeficiency characterized by impaired humoral immune responses and reduced cellular responses of B-cells similar to X-linked immunodeficiency (Xid). Mice are unable to activate NF-kappa-B and promote cell survival in B-cells upon BCR signaling, or even in mast cells. B-cells fail to recruit the I-kappa-B kinase (IKK) complex into lipid rafts, activate IKK, degrade I-kappa-B or up-regulate NF-kappa-B-dependent survival signals. Moreover, mutant animals are hyperphagic and exhibit higher food intake and reduced feed efficiency versus wild type. Mice are considerably leaner and display markedly decreased size of white fat depots. Triglyceride content in the liver and skeletal muscle is also significantly low.|||Nucleus|||Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity (By similarity). Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade. http://togogenome.org/gene/10090:Or4k15 ^@ http://purl.uniprot.org/uniprot/A2RTN7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sgta ^@ http://purl.uniprot.org/uniprot/Q3TN35|||http://purl.uniprot.org/uniprot/Q8BJU0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SGT family.|||Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails. Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module. Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins. It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states. Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex. Binds directly to HSC70 and HSP70 and regulates their ATPase activity.|||Cytoplasm|||Homodimer (By similarity). Homooligomer (By similarity). Interacts with DNAJC5 and DNAJC5B (PubMed:17034881). Interacts (via TPR repeats) with HSP90AA1. Interacts (via Gln-rich region) with SLC2A1 (By similarity). Interacts with HSP90AB1 (By similarity). Interacts (via TPR repeats) with HSPA8/Hsc70; the interaction is direct (By similarity). Interacts with BAG6 (via ubiquitin-like domain); interaction prevents interaction between BAG6 and RNF126 (By similarity). Forms a multiprotein complex, at least composed of DNAJB12, DNAJB14, HSPA8/Hsc70 and SGTA; interaction with DNAJB14 and HSPA8/Hsc70 is direct (By similarity).|||Nucleus http://togogenome.org/gene/10090:Rtl4 ^@ http://purl.uniprot.org/uniprot/Q3URY0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Tissue Specificity ^@ Expressed at 12.5 dpc in almost all tissues tested. Expressed at 14.5 dpc in brain, eye and liver. Weakly expressed in lung, heart and kidney.|||In adults, expressed in brain, eye, kidney, ovary and testis (PubMed:26402067, PubMed:15716091). Weakly expressed in thymus, heart and muscle (PubMed:15716091).|||Involved in cognitive function in the brain, possibly via the noradrenergic system.|||Mutants are viable and don't show growth retardation in the pre- and postnatal periods in either female or male mice (PubMed:26402067). Animals are fertile, even in the case of mating between mutants. They exhibit abnormal behaviors related to cognition, including attention, impulsivity, and working memory (PubMed:26402067). Animals show a reduced recovery rate of noradrenaline in the prefrontal cortex region (PubMed:26402067).|||RTL4 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes. http://togogenome.org/gene/10090:Cd5l ^@ http://purl.uniprot.org/uniprot/Q9QWK4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with FASN; the interaction is direct (PubMed:20519120). Interacts with IgM; protecting CD5L from renal excretion and leading to increased CD5L levels in circulating blood (PubMed:23562157).|||Mice are apparently healthy under specific pathogen-free conditions. However, thymus of mice display much fewer thymocytes and CD4/CD8 double-positive (DP) thymocytes are more susceptible to apoptosis (PubMed:9892623). Increased adipocyte size and adipose tissue mass (PubMed:20519120). Higher level of free cholesterol in Th17 cells (PubMed:26607793).|||N-glycosylated (PubMed:10651944, PubMed:23236605). N-glycan at Asn-99 possesses only alpha2,6-sialylated terminals, while Asn-229 possesses both alpha2,6-sialylated and non-sialylated terminals (PubMed:23236605). N-glycosylation increases secretion.|||Secreted|||Secreted protein that acts as a key regulator of lipid synthesis: mainly expressed by macrophages in lymphoid and inflamed tissues and regulates mechanisms in inflammatory responses, such as infection or atherosclerosis (PubMed:26048980). Able to inhibit lipid droplet size in adipocytes (PubMed:20519120, PubMed:22579686). Following incorporation into mature adipocytes via CD36-mediated endocytosis, associates with cytosolic FASN, inhibiting fatty acid synthase activity and leading to lipolysis, the degradation of triacylglycerols into glycerol and free fatty acids (FFA) (PubMed:20519120). CD5L-induced lipolysis occurs with progression of obesity: participates in obesity-associated inflammation following recruitment of inflammatory macrophages into adipose tissues, a cause of insulin resistance and obesity-related metabolic disease (PubMed:21730133). Regulation of intracellular lipids mediated by CD5L has a direct effect on transcription regulation mediated by nuclear receptors ROR-gamma (RORC) (PubMed:22579686, PubMed:26607793). Acts as a key regulator of metabolic switch in T-helper Th17 cells (PubMed:26607794, PubMed:26607793). Regulates the expression of pro-inflammatory genes in Th17 cells by altering the lipid content and limiting synthesis of cholesterol ligand of RORC, the master transcription factor of Th17-cell differentiation (PubMed:26607793). CD5L is mainly present in non-pathogenic Th17 cells, where it decreases the content of polyunsaturated fatty acyls (PUFA), affecting two metabolic proteins MSMO1 and CYP51A1, which synthesize ligands of RORC, limiting RORC activity and expression of pro-inflammatory genes (PubMed:26607793). Participates in obesity-associated autoimmunity via its association with IgM, interfering with the binding of IgM to Fcalpha/mu receptor and enhancing the development of long-lived plasma cells that produce high-affinity IgG autoantibodies (PubMed:23562157). Also acts as an inhibitor of apoptosis in macrophages: promotes macrophage survival from the apoptotic effects of oxidized lipids in case of atherosclerosis (PubMed:9892623, PubMed:16054063). Involved in early response to microbial infection against various pathogens by acting as a pattern recognition receptor and by promoting autophagy (By similarity).|||Specifically expressed in tissue macrophages (PubMed:9892623). Expressed in thymus, liver, spleen and lymph nodes (PubMed:10651944). Present in Th17 cells; mainly present in non-pathogenic Th17 cells (PubMed:26607793).|||Transcription is activated by nuclear receptor liver X /retinoid X (RXR/LXR). http://togogenome.org/gene/10090:Or5w10 ^@ http://purl.uniprot.org/uniprot/Q7TR47 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ucp3 ^@ http://purl.uniprot.org/uniprot/B2RTM2|||http://purl.uniprot.org/uniprot/P56501 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Homozygous knockout mice lacking Ucp3 show no overt phenotype being born at the expected frequency, with no observed signs of abnormality, illness, or increased mortality at up to one year of age. They are not obese and have reduced free fatty acids and glucose serum levels. They show a normal circadian rhythm in body temperature and motor activity and have normal body temperature responses to fasting, stress, thyroid hormone, and cold exposure. The baseline metabolic rate and respiratory exchange ratio are the same in knockout and control mice. However, there is decreased proton leak in the mitochondria over the complete range of metabolic rates studied (PubMed:10748195, PubMed:10748196). Mitochondria are more coupled and the production of reactive oxygen species is increased. No effect on exercise tolerance and fatty acid oxidation is observed (PubMed:10748196).|||Inhibited by purine nucleotides and inorganic phosphate (in vitro).|||Interacts with HAX1; the interaction is direct and calcium-dependent.|||Membrane|||Mitochondrion inner membrane|||Putative transmembrane transporter that plays a role in mitochondrial metabolism via an as yet unclear mechanism (PubMed:10748195, PubMed:10748196). Originally, this mitochondrial protein was thought to act as a proton transmembrane transporter from the mitochondrial intermembrane space into the matrix, causing proton leaks through the inner mitochondrial membrane, thereby uncoupling mitochondrial membrane potential generation from ATP synthesis (PubMed:29212043). However, this function is controversial and uncoupling may not be the function, or at least not the main function, but rather a consequence of more conventional metabolite transporter activity (PubMed:11707458, PubMed:20363757). http://togogenome.org/gene/10090:Ppip5k2 ^@ http://purl.uniprot.org/uniprot/Q6ZQB6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the histidine acid phosphatase family. VIP1 subfamily.|||Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096). Required for normal hearing (PubMed:29590114).|||The C-terminal acid phosphatase-like domain binds PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity.|||Ubiquitously expressed (PubMed:29590114). Expressed in the cochlear and vestibular sensory hair cells, supporting cells and spiral ganglion neurons (PubMed:29590114).|||cytosol http://togogenome.org/gene/10090:Dock6 ^@ http://purl.uniprot.org/uniprot/A0A1L1SQR4|||http://purl.uniprot.org/uniprot/Q8VDR9 ^@ Developmental Stage|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as guanine nucleotide exchange factor (GEF) for CDC42 and RAC1 small GTPases (By similarity). Through its activation of CDC42 and RAC1, regulates neurite outgrowth in an vitro differentiation system.|||Belongs to the DOCK family.|||Contaminating sequence. Vector contamination at the N-terminus.|||Cytoplasm|||Expressed at 9.5 dpc in the growing edge of the limb buds and in the developing heart. At 10.5 dpc, strongly expressed at the edge of the limb buds, while expression in the heart maintained. At 11.5 dpc, detected in the apical ectodermal ridge of all 4 limbs, with higher expression in hindlimbs than in forelimbs. By 12.5 and 13.5 dpc, expression pattern more diffused in the limbs. At 13.5 dpc, clearly observed in the developing digits.|||The DOCKER domain may mediate some GEF activity.|||Up-regulated during differentiation of the N1E-115 neuroblastoma cell line.|||Widely expressed with highest levels in lung and heart.|||perinuclear region http://togogenome.org/gene/10090:Anxa7 ^@ http://purl.uniprot.org/uniprot/A0A2C9F2D2|||http://purl.uniprot.org/uniprot/Q07076|||http://purl.uniprot.org/uniprot/Q3UYL7|||http://purl.uniprot.org/uniprot/Q8CCV9 ^@ Domain|||Function|||Similarity|||Subunit ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis.|||Interacts with PDCD6. http://togogenome.org/gene/10090:Defb23 ^@ http://purl.uniprot.org/uniprot/Q30KP0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Nlgn3 ^@ http://purl.uniprot.org/uniprot/Q8BYM5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Brain and arteries (at protein level). Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Expressed in olfactory bulb and olfactory epithelium. Found in olfactory ensheathing glia but not in olfactory neurons, and in developing peripheral glia.|||Cell membrane|||Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. May also play a role in glia-glia or glia-neuron interactions in the developing peripheral nervous system.|||Detected at embryonic day 17 dpc and postnatal day P1 in retinal astrocytes, spinal cord astrocytes and Schwann cells of the dorsal root ganglion.|||Homodimer, and heterodimer with NLGN1 and NLGN2 (By similarity). Interacts with neurexins NRXN1, NRXN2 and NRXN3 (By similarity). Interaction with neurexins is mediated by heparan sulfate glycan modification on neurexin (PubMed:30100184). Interacts (via its C-terminus) with DLG4/PSD-95 (via PDZ domain 3) (By similarity).|||No obvious phenotype, but mice present subtle behavorial changes with reduced ultrasound vocalization and impaired response to olfactory cues. In addition, mice have reduced brain volume. Mice lacking both NLGN1 and NLGN3, or NLGN2 and NLGN3, are viable, but have impaired breathing, drastically reduced reproduction rates and striking deficits in raising their offspring. Mice lacking NLGN1, NLGN2 and NLGN3 are born at the expected Mendelian rate, but die shortly after birth due to respiratory failure. They do not show a significant change in the number of synapses, but synapse function is strongly impaired.|||Synapse http://togogenome.org/gene/10090:Slc36a2 ^@ http://purl.uniprot.org/uniprot/Q8BHK3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Electrogenic proton/amino acid symporter with a high selectivity for the small side chains amino acids glycine, alanine and proline, where both L- and D-enantiomers are transported. Extension of the backbone length, as in beta-alanine and 4-aminobutanoate or methylation of the amino group, as in sarcosine and N,N-dimethylglycine, are also tolerated but decrease transport efficiency. A free carboxyl group is preferred.|||Endoplasmic reticulum membrane|||Expressed in spinal cord, brain, testis, lung, heart, colon, spleen, kidney and muscle. Found in neuronal cell bodies in the anterior horn, in spinal cord brain stem, cerebellum, hippocampus, hypothalamus, rhinencephalon, cerebral cortex, and olfactory bulb in the brain. Also expressed in bone and fat tissues.|||Recycling endosome membrane http://togogenome.org/gene/10090:Rbl2 ^@ http://purl.uniprot.org/uniprot/A0A1B0GR06|||http://purl.uniprot.org/uniprot/A0A1B0GRM0|||http://purl.uniprot.org/uniprot/Q64700 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the retinoblastoma protein (RB) family.|||During G0 and early G1 phase of the cell cycle, phosphorylated on Ser-636 and on 5 sites within the domain B. Phosphorylation on Ser-669 in G1 leads to its ubiquitin-dependent proteolysis (By similarity).|||Interacts with AATF and RINT1. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with USP4 (By similarity). Interacts with KMT5B, KMT5C and USP4. Interacts with PML (By similarity). Interacts with RBBP9 (By similarity).|||Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.|||Nucleus http://togogenome.org/gene/10090:Slc23a4 ^@ http://purl.uniprot.org/uniprot/A0A0J9YUX7|||http://purl.uniprot.org/uniprot/E9PW54|||http://purl.uniprot.org/uniprot/Q6DIB3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.|||Membrane http://togogenome.org/gene/10090:Rhox4a ^@ http://purl.uniprot.org/uniprot/Q9D3I8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Slc6a17 ^@ http://purl.uniprot.org/uniprot/A0A0R4J087|||http://purl.uniprot.org/uniprot/Q8BJI1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Expressed during embryonic brain development and the highest levels are observed postnatally.|||Expressed in the brain. The strongest expression levels in embryonic, postnatal, and adult stages are found in both cortical and hippocampal tissues.|||Membrane|||Postsynapse|||Presynapse|||Synaptic vesicle transporter with apparent selectivity for neutral amino acids. The transport is sodium-coupled but chloride-independent, likely driven by the proton electrochemical gradient generated by vacuolar H(+)-ATPase in an overall electrogenic mechanism. May contribute to the synaptic uptake of neurotransmitter precursors in a process coupled in part to vesicle exocytosis.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Acot13 ^@ http://purl.uniprot.org/uniprot/Q4VA32|||http://purl.uniprot.org/uniprot/Q9CQR4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the thioesterase PaaI family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:19405909). Has acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates (PubMed:19405909). Can also hydrolyze 3-hydroxyphenylacetyl-CoA and 3,4-dihydroxyphenylacetyl-CoA (in vitro) (By similarity). May play a role in controlling adaptive thermogenesis (PubMed:24072708).|||Highly expressed in the kidney and moderately in the heart, liver, brain, small and large intestine. Also expressed in brown adipose tissue.|||Homotetramer. Interacts with PCTP.|||Mitochondrion|||No visible phenotype until 7 weeks of age. Animals are viable and fertile. After 7 weeks, mutant mice exhibit a modest decrease in body weight and decreased adiposity, compared to wild-type animals, despite increased food consumption. They tend to show a reduced hepatic fatty acyl-CoA thioesterase activity, leading to alterations in fatty acid metabolism and improved glucose homeostasis. When fed a high-fat diet, mutant livers are protected against steatosis and increased hepatic glucose production (PubMed:22345407). Mutant mice adapt more rapidly than wild-type to short-term cold exposure by increasing physical activity, food consumption and energy expenditure. After 96-hour equilibration at cold temperature, genotype-dependent differences are abolished. Mutant brown adipose tissue show reduced lipid droplets, alterations in the ultrastructure of mitochondria and a small increase in the expression of thermogenic genes (PubMed:24072708).|||Nucleus|||cytosol|||spindle http://togogenome.org/gene/10090:Wdr83 ^@ http://purl.uniprot.org/uniprot/Q9DAJ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat MORG1 family.|||Cytoplasm|||Interacts with EGLN3/PHD3. Identified in the spliceosome C complex (By similarity). Interacts with ERK signaling proteins MAP2K1/MEK1, MAP2K2/MEK2, LAMTOR3, ARAF/Raf-1, MAPK1/ERK2 and MAPK3/ERK1.|||Molecular scaffold protein for various multimeric protein complexes. Involved in response to hypoxia by acting as a negative regulator of HIF1A/HIF-1-alpha via its interaction with EGLN3/PHD3. May promote degradation of HIF1A. May act by recruiting signaling complexes to a specific upstream activator (By similarity). Also acts as a module in the assembly of a multicomponent scaffold for the ERK pathway, linking ERK responses to specific agonists. At low concentrations it enhances ERK activation, whereas high concentrations lead to the inhibition of ERK activation. May also be involved in pre-mRNA splicing.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Vax1 ^@ http://purl.uniprot.org/uniprot/Q2NKI2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ At 9.5 dpc, expressed in the forebrain, through the optic stalk and ending in the proximal portion of the optic vesicle. At 10.5 dpc, expressed in the optic stalk, outer layer of the optic cup, and the primordium of the pigment epithelium. In the pigment epithelium, down-regulated after 11.5 dpc, and expression restricted to the optic stalk and the ventral forebrain.|||Belongs to the EMX homeobox family.|||Nucleus|||Transcription factor that may function in dorsoventral specification of the forebrain. Required for axon guidance and major tract formation in the developing forebrain. May contribute to the differentiation of the neuroretina, pigmented epithelium and optic stalk. http://togogenome.org/gene/10090:Braf ^@ http://purl.uniprot.org/uniprot/P28028 ^@ Activity Regulation|||Cofactor|||Disease Annotation|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||Chimeric cDNA.|||Cytoplasm|||In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains. Following mitogen-mediated cell activation, binds via its RGB domain to active HRAS (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains. This allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which activates BRAF.|||Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway. Phosphorylates PFKFB2 (By similarity). May play a role in the postsynaptic responses of hippocampal neurons.|||Methylation by PRMT5 decreases stability and kinase activity.|||Monomer (By similarity). Homodimer (By similarity). Heterodimerizes with RAF1, and the heterodimer possesses a highly increased kinase activity compared to the respective homodimers or monomers (By similarity). Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can induce a negative feedback that promotes the dissociation of the heterodimer by phosphorylating BRAF at Thr-738. Heterodimerizes (via N-terminus) with KSR1 (via N-terminus) or KSR2 (via N-terminus) in a MAP2K1-dependent manner (By similarity). Interacts with MAP2K1 and MAP2K2 (By similarity). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIT1. Interacts (via N-terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with RAF1, a ternary complex inhibited by GNAI1 (By similarity). Interacts with DGKH (By similarity). Interacts with PRMT5 (By similarity). Interacts with AKAP13, MAP2K1 and KSR1. Identified in a complex with AKAP13, KSR1 and MAP2K1 (PubMed:21102438). Interacts with FNIP1 and FNIP2 (By similarity).|||Nucleus|||Participates in a chromosomal translocation that produces a Tif1a-BRAF (T18) oncogene originally isolated from a furfural-induced hepatoma.|||Phosphorylation at Ser-348 by SGK1 inhibits its activity.|||Ubiquitinated by RNF149; which leads to proteasomal degradation. Polyubiquitinated at Lys-615 in response to EGF (By similarity). http://togogenome.org/gene/10090:Nrtn ^@ http://purl.uniprot.org/uniprot/P97463 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family. GDNF subfamily.|||Homodimer; disulfide-linked.|||Secreted|||Supports the survival of sympathetic neurons in culture. May regulate the development and maintenance of the CNS. Might control the size of non-neuronal cell population such as haemopoietic cells.|||Widespread distribution. http://togogenome.org/gene/10090:Alk ^@ http://purl.uniprot.org/uniprot/P97793 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated upon ALKAL2 ligand-binding. ALKAL2-driven activation is coupled with heparin-binding (By similarity). Following ligand-binding, homodimerizes and autophosphorylates, activating its kinase activity (By similarity). Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Homodimer; homodimerizes following heparin- and ligand-binding (By similarity). Interacts with CBL, IRS1, PIK3R1 and PLCG1 (PubMed:15226403, PubMed:16878150). Interacts with FRS2 and SHC1 (PubMed:15226403, PubMed:16878150). Interacts with PTN and MDK (By similarity).|||In the hypothalamus, expression is induced in response to feeding.|||Mainly expressed in central nervous system (CNS) and other parts of the brain such as the paraventricular nucleus (PVN) of the hypothalamus. Expression is also found in peripheral nervous systems, eye, nasal epithelium, olfactory nerve, tongue, skin, tissue surrounding the esophagus, stomach, midgut, as well as testis and ovary.|||Mice display a decrease in newborn neurons and defects in brain function (PubMed:17487225, PubMed:22079349). Mice show an age-dependent increase in basal hippocampal progenitor proliferation and alterations in behavioral tests (PubMed:17487225). Mice lacking both Alk and Ltk show a strong reduction in newborn neurons (PubMed:22079349). Mutants develop a thin phenotype at the age of 5 weeks, persisting into adulthood with reduced body adiposity, elevated adiponectin levels and improved glucose homeostasis, while having unaltered food intake and activity (PubMed:32442405). They show a marked resistance to diet- and leptin-mutation-induced obesity and exhibit increased adipose tissue lipolysis (PubMed:32442405).|||Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:15226403, PubMed:16458083, PubMed:16878150, PubMed:19200234, PubMed:30497772). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (PubMed:32442405). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response. In contrast, ALKAL1 is not a potent physiological ligand for ALK. Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (By similarity).|||Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. In cells not stimulated by a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are undergoing autophosphorylation through autoactivation.|||The EGF-like region drives the cytokine specificity for ALKAL2.|||The heparin-binding region binds heparin glycosaminoglycan. Heparin-binding is required for ALKAL2-driven activation. http://togogenome.org/gene/10090:Ccdc85c ^@ http://purl.uniprot.org/uniprot/A0A217FL83|||http://purl.uniprot.org/uniprot/E9Q6B2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC85 family.|||Disrupted in the hemorrhagic hydrocephalus (hhy) mutant. The mutant animals shown sucortical heterotopia and non-obstructive hydrocephalus with frequent brain hemorrhage.|||May interact with ARVCF, CTNND1, CTNND2 and PKP4.|||May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family (By similarity). May play an important role in cortical development, especially in the maintenance of radial glia (PubMed:22056358).|||Predominantly expressed on the surface of the lateral ventricular walls of the developing cerebral cortex.|||adherens junction|||tight junction http://togogenome.org/gene/10090:Epb41 ^@ http://purl.uniprot.org/uniprot/A0A068WAQ5|||http://purl.uniprot.org/uniprot/A0A068WAZ7|||http://purl.uniprot.org/uniprot/A0A571BEG4|||http://purl.uniprot.org/uniprot/P48193 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds with a high affinity to glycophorin and with lower affinity to band III protein. Associates with the nuclear mitotic apparatus. Binds calmodulin, CENPJ and DLG1. Also found to associate with contractile apparatus and tight junctions. Interacts with NUMA1; this interaction is negatively regulated by CDK1 during metaphase and promotes anaphase-specific localization of NUMA1 in symmetrically dividing cells. Interacts with ATP2B1; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1 (PubMed:23460639).|||Nucleus|||O-glycosylated; contains N-acetylglucosamine side chains in the C-terminal domain.|||Phosphorylated at multiple sites by different protein kinases and each phosphorylation event selectively modulates the protein's functions.|||Phosphorylation on Tyr-654 reduces the ability of 4.1 to promote the assembly of the spectrin/actin/4.1 ternary complex.|||Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Kif5b ^@ http://purl.uniprot.org/uniprot/Q61768 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin subfamily.|||Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.|||Cytolytic granule membrane|||Lysosome membrane|||Mice are embryonic lethal. They show perinuclear clustering of mitochondria and impaired lysosomal dispersion.|||Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. May be involved in the mechanisms of growth arrest induced by exposure to DNA-damaging drugs or by cellular senescence (PubMed:9657148). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (PubMed:21976701). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends. Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (By similarity).|||Oligomer composed of two heavy chains and two light chains. Interacts with GRIP1 and PPP1R42 (PubMed:11986669, PubMed:19886865). Interacts with SYBU (By similarity). Interacts with JAKMIP1 (PubMed:17532644). Interacts with PLEKHM2. Interacts with ECPAS (By similarity). Interacts with ZFYVE27 (PubMed:21976701). Found in a complex with OGT, RHOT1, RHOT2 and TRAK1 (By similarity). Interacts with APP (via cytoplasmic domain) (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Fuom ^@ http://purl.uniprot.org/uniprot/Q8R2K1 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RbsD / FucU family.|||Deficient female mice show reduced sexual receptivity, as measured by lordosis quotient and masculinized sexual behaviors in female mice. Display a reduced number of tyrosine hydroxylase-positive neurons in the anteroventral periventricular nucleus, a sexually dimorphic feature in rats and mice. Embryos at 16.5 dpc have reduced alpha-feto-protein levels and reduced fucosylation of alpha-feto-protein.|||Involved in the interconversion between alpha- and beta-L-fucoses. L-Fucose (6-deoxy-L-galactose) exists as alpha-L-fucose (29.5%) and beta-L-fucose (70.5%), the beta-form is metabolized through the salvage pathway. GDP-L-fucose formed either by the de novo or salvage pathways is transported into the endoplasmic reticulum, where it serves as a substrate for N- and O-glycosylations by fucosyltransferases. Fucosylated structures expressed on cell surfaces or secreted in biological fluids are believed to play a critical role in cell-cell adhesion and recognition processes.|||Mainly homodimer, but exists also as homotetramer, homooctamer, and homodecamer. The homodimeric form seems catalytically inactive.|||Widely expressed in various tissues and cell lines, including kidney, liver, and pancreas, marginally in muscle and testis. http://togogenome.org/gene/10090:Rnf26 ^@ http://purl.uniprot.org/uniprot/Q8BUH7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin-protein ligase that plays a key role in endosome organization by retaining vesicles in the perinuclear cloud. Acts as a platform for perinuclear positioning of the endosomal system by mediating ubiquitination of SQSTM1 through interaction with the ubiquitin conjugating enzyme UBE2J1. Ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Also acts as a regulator of type I interferon production in response to viral infection by mediating the formation of 'Lys-11'-linked polyubiquitin chains on TMEM173/STING, leading to stabilize TMEM173/STING. Also required to limit type I interferon response by promoting autophagic degradation of IRF3.|||Endoplasmic reticulum membrane|||Interacts with INCA1. Interacts with TMEM43, ENDOD1, TMEM33 and TMED1 to form a complex capable of modulating innate immune signaling through the cGAS-STING pathway. Interacts with UBE2J1; this interaction is important for SQSTM1 ubiquitination. http://togogenome.org/gene/10090:Usp16 ^@ http://purl.uniprot.org/uniprot/Q99LG0 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. USP16 subfamily.|||Cytoplasm|||Homotetramer. Associates with late pre-40S ribosomes.|||Nucleus|||Phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. Phosphorylation by AURKB enhances the deubiquitinase activity.|||Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis. In resting B- and T-lymphocytes, phosphorylation by AURKB leads to enhance its activity, thereby maintaining transcription in resting lymphocytes (PubMed:24034696). Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B. Also deubiquitinates non-histone proteins, such as ribosomal protein RPS27A: deubiquitination of monoubiquitinated RPS27A promotes maturation of the 40S ribosomal subunit.|||The UBP-type zinc finger binds 3 zinc ions that form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. It recognizes the C-terminal tail of free ubiquitin.|||Usp16 acts as a regulator of stem cell self-renewal and its overexpression contributes to somatic stem cell defects observed in Down syndrome models in mouse. Usp16 is triplicated in Ts65D Down syndrome mouse model and its overexpression leads to reduce the self-renewal of haematopoietic stem cells and the expansion of mammary epithelial cells, neural progenitors and fibroblasts. Defects are rescued by down-regulating Usp16 in Ts65D mice by short interfering RNAs (PubMed:24025767). http://togogenome.org/gene/10090:Vmn1r107 ^@ http://purl.uniprot.org/uniprot/D3YTY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cct5 ^@ http://purl.uniprot.org/uniprot/P80316 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG (By similarity). Interacts with DNAAF4 (PubMed:23872636). Interacts with DLEC1 (By similarity). Interacts with SPMAP2 (PubMed:10747865).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||The N-terminus is blocked.|||Ubiquitinated by the DCX(DCAF12) complex specifically recognizes the diglutamate (Glu-Glu) at the C-terminus, leading to its degradation.|||centrosome http://togogenome.org/gene/10090:Slc7a15 ^@ http://purl.uniprot.org/uniprot/Q50E62|||http://purl.uniprot.org/uniprot/Q8BZV2|||http://purl.uniprot.org/uniprot/Q9D8H4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Skint2 ^@ http://purl.uniprot.org/uniprot/A7XUX6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin, thymus and mammary gland.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Eif3g ^@ http://purl.uniprot.org/uniprot/Q544H0|||http://purl.uniprot.org/uniprot/Q9Z1D1 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit G family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of FRAP1 and RAPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts (via C-terminus) with AIFM1 (via N-terminus).|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts (via C-terminus) with AIFM1 (via N-terminus) (By similarity). Interacts with DHX33; the interaction is independent of RNA (PubMed:26100019).|||Cytoplasm|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation.|||RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. This subunit can bind 18S rRNA.|||perinuclear region http://togogenome.org/gene/10090:Sigmar1 ^@ http://purl.uniprot.org/uniprot/A2AMS0|||http://purl.uniprot.org/uniprot/B7ZJH6|||http://purl.uniprot.org/uniprot/B7ZJH7|||http://purl.uniprot.org/uniprot/B7ZJH8|||http://purl.uniprot.org/uniprot/B7ZJH9|||http://purl.uniprot.org/uniprot/I4DCY6|||http://purl.uniprot.org/uniprot/O55242 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ERG2 family.|||Cell junction|||Cell membrane|||Cytoplasmic vesicle|||Depletion by RNAi enhances kappa-type opioid receptor-mediated analgesia and prevents the memory-improving effects of (-)- and (+)-pentazocine.|||Endoplasmic reticulum membrane|||Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane (PubMed:12730355). Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:11149946, PubMed:14622179, PubMed:15571673, PubMed:15777781, PubMed:23332758, PubMed:9425306, PubMed:9603192). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (PubMed:25678561). Plays a role in protecting cells against oxidative stress-induced cell death via its interaction with RNF112 (PubMed:26792191).|||Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Regulates calcium efflux at the endoplasmic reticulum.|||Homotrimer (By similarity). Interacts with KCNA4 (By similarity). Interacts with KCNA2; cocaine consumption leads to increased interaction (PubMed:23332758). Forms a ternary complex with ANK2 and ITPR3. The complex is disrupted by agonists (PubMed:11149946). Interacts with RNF112 in an oxidative stress-regulated manner (PubMed:26792191).|||Homotrimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lipid droplet|||Membrane|||Mice display decreased hypermotility response induced by (+)SKF-10047 challenge and reduced formalin-induced pain (PubMed:14622179). Mice display motor coordination defects, muscle weakness, partial neuromuscular junction innervation, and motor neuron degeneration (PubMed:20167253, PubMed:25678561).|||Nucleus envelope|||Nucleus inner membrane|||Nucleus outer membrane|||Postsynaptic density membrane|||Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile.|||The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane.|||Vesicle|||Widely expressed with higher expression in liver, brain, kidney and thymus. Expressed throughout the brain with higher expression within cerebral cortex, hippocampus and cerebellum. Within the hippocampus expressed in cornu ammonis pyramidal neurons, the granular cells of the dentate gyrus as well as interneurons. Within the cerebellum, expressed in Purkinje cell bodies (PubMed:11207432, PubMed:11476895, PubMed:11687279, PubMed:9603192). Highly expressed in the brainstem and motor neurons of the spinal cord (PubMed:20167253). Expressed by neural retina, retinal pigment epithelial cells and lens (PubMed:11207432, PubMed:11476895, PubMed:11687279, PubMed:9603192).|||growth cone http://togogenome.org/gene/10090:Cyp4v3 ^@ http://purl.uniprot.org/uniprot/B2RSR0|||http://purl.uniprot.org/uniprot/Q9DBW0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in fatty acid metabolism in the eye. Catalyzes the omega-hydroxylation of polyunsaturated fatty acids (PUFAs) docosahexaenoate (DHA) and its precursor eicosapentaenoate (EPA), and may contribute to the homeostasis of these retinal PUFAs. Omega hydroxylates saturated fatty acids such as laurate, myristate and palmitate, the catalytic efficiency decreasing in the following order: myristate > laurate > palmitate (C14>C12>C16). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Inhibited by N-hydroxy-N'-(4-n-butyl-2-methylphenyl formamidine)(HET0016) with an IC(50) of 38 nM. http://togogenome.org/gene/10090:Smpdl3a ^@ http://purl.uniprot.org/uniprot/P70158 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the acid sphingomyelinase family.|||Binds 2 Zn(2+) per subunit.|||Detected in blood serum (at protein level).|||Has in vitro nucleotide phosphodiesterase activity with nucleoside triphosphates, such as ATP (PubMed:26792860). Has in vitro activity with p-nitrophenyl-TMP. Has lower activity with nucleoside diphosphates, and no activity with nucleoside monophosphates. Has in vitro activity with CDP-choline, giving rise to CMP and phosphocholine. Has in vitro activity with CDP-ethanolamine. Does not have sphingomyelin phosphodiesterase activity (By similarity).|||N-glycosylated.|||Requires micromolar levels of Zn(2+) for activity. Inhibited by millimolar levels of Zn(2+).|||Secreted http://togogenome.org/gene/10090:Axin2 ^@ http://purl.uniprot.org/uniprot/O88566|||http://purl.uniprot.org/uniprot/Q3UQK5 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway.|||Cytoplasm|||Expressed in Tcf7-positive innate-like T-cells (at protein level).|||Expressed in the distal tooth bud epithelium during the bud stage of mandibular molar tooth development.|||Inhibitor of the Wnt signaling pathway. Down-regulates beta-catenin. Probably facilitate the phosphorylation of beta-catenin and APC by GSK3B.|||Interacts with glycogen synthase kinase-3 beta (GSK3B) and beta-catenin. The interaction between axin and beta-catenin occurs via the armadillo repeats contained in beta-catenin. Interacts with SMAD7 and RNF111 (By similarity). Interacts with ANKRD6 (PubMed:12183362). Interacts with SIAH1 (By similarity). Interacts with SIAH2 (By similarity).|||Probably phosphorylated by GSK3B and dephosphorylated by PP2A.|||The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2.|||Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription. http://togogenome.org/gene/10090:Mcm3 ^@ http://purl.uniprot.org/uniprot/P25206|||http://purl.uniprot.org/uniprot/Q3UI57 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by MCM3AP.|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division.|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Belongs to the MCM family.|||Chromosome|||Component of the MCM2-7 complex.|||Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (By similarity). Associated with the replication-specific DNA polymerase alpha (PubMed:7925275). Interacts with MCMBP (By similarity). Interacts with ANKRD17 (By similarity). Interacts with MCM3AP; this interaction leads to MCM3 acetylation (PubMed:10733502).|||Nucleus|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. http://togogenome.org/gene/10090:Txndc17 ^@ http://purl.uniprot.org/uniprot/Q9CQM5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thioredoxin family.|||Cytoplasm|||Disulfide reductase. May participate in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions. Modulates TNF-alpha signaling and NF-kappa-B activation. Has peroxidase activity and may contribute to the elimination of cellular hydrogen peroxide (By similarity).|||Interacts with TRXR1 and DYNLL1/DNCL1.|||The oxidized protein is reduced by TRXR1. http://togogenome.org/gene/10090:Spo11 ^@ http://purl.uniprot.org/uniprot/Q9WTK8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TOP6A family.|||Component of a topoisomerase 6 complex specifically required for meiotic recombination. Together with TOP6BL, mediates DNA cleavage that forms the double-strand breaks (DSB) that initiate meiotic recombination (PubMed:26917764). The complex promotes relaxation of negative and positive supercoiled DNA and DNA decatenation through cleavage and ligation cycles. Essential for the phosphorylation of SMC3, HORMAD1 and HORMAD2 (PubMed:22346761).|||Does not interact with TOP6BL (PubMed:26917764).|||Heterotetramer of SPO11 and 2 TOP6BL chains (Probable). Interacts with TOP6BL (PubMed:26917764).|||High levels are found only in the testis where expression is restricted primarily to meiotic germ cells. Not expressed in spermatogonia. Highest levels are found in pachytene spermatocytes. Very low levels are found in thymus, brain and oocytes of embryonic ovary. Not detected in adult ovary (PubMed:10622720, PubMed:10855504). Isoform 1: Expressed early in meiosis, when most double-strand breaks (DSB) are formed (PubMed:21330546).|||In contrast to isoform 1, does not mediate DNA cleavage that forms the double-strand breaks (DSB) that initiate meiotic recombination.|||Not detected at day 7 postpartum (dpp). Levels are low at 12 dpp but increase by 17 dpp. High levels are maintained throughout the remainder of testis development.|||Nucleus http://togogenome.org/gene/10090:Camk2d ^@ http://purl.uniprot.org/uniprot/A0A0G2JGS4|||http://purl.uniprot.org/uniprot/E9Q1T1|||http://purl.uniprot.org/uniprot/E9Q1W0|||http://purl.uniprot.org/uniprot/Q6PHZ2|||http://purl.uniprot.org/uniprot/Q8CCM0 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.|||Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with RRAD (By similarity). Interacts with CACNB2.|||Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport (PubMed:12676814, PubMed:15456698, PubMed:17124532). Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure (PubMed:12676814, PubMed:19381018, PubMed:19179290). Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808' (PubMed:20194790). In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction (PubMed:15793582). In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure (PubMed:17124532). Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023).|||Expressed in cardiac muscle and skeletal muscle. Isoform Delta 2, isoform Delta 6, isoform Delta 6 and isoform Delta 10 are expressed in cardiac muscle. Isoform Delta 2 is expressed in skeletal muscle.|||Mice overexpressing CaMK2D develop a dilated cardiomyopathy, enlarged myocytes with reduced contractility and altered Ca(2+) handling, and die prematurely in PubMed:12676814.|||Sarcoplasmic reticulum membrane|||The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.|||sarcolemma http://togogenome.org/gene/10090:Sec24a ^@ http://purl.uniprot.org/uniprot/A2AA71|||http://purl.uniprot.org/uniprot/Q3U2P1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC23/SEC24 family. SEC24 subfamily.|||COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1. Interacts with TMED2. Interacts (as part of the Sec23/24 complex) with SEC22B; recruits SEC22B into COPII-coated vesicles for its transport from the endoplasmic reticulum to the Golgi (By similarity). Interacts with STING1; promoting STING1 translocation to COPII vesicles in a STEEP1-dependent manner (By similarity). Interacts with TMEM39A (By similarity). Interacts with SACM1L; this interaction is reduced in the absence of TMEM39A (By similarity). Interacts with kinase FAM20C; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles (By similarity).|||COPII-coated vesicle membrane|||Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex. Plays a central role in cargo selection within the COPII complex and together with SEC24B may have a different specificity compared to SEC24C and SEC24D. May package preferentially cargos with cytoplasmic DxE or LxxLE motifs and may also recognize conformational epitopes.|||Endoplasmic reticulum membrane|||Membrane|||cytosol http://togogenome.org/gene/10090:Tnrc6c ^@ http://purl.uniprot.org/uniprot/B1ATC3|||http://purl.uniprot.org/uniprot/Q3UHC0 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the GW182 family.|||Interacts with one or more of the argonaute family proteins AGO1, AGO2, AGO3 and AGO4. Interacts with CNOT1; the interaction mediates the association with the CCR4-NOT complex. Interacts with PAN3; the interaction mediates the association with the PAN complex (By similarity).|||Plays a role in RNA-mediated gene silencing by micro-RNAs (miRNAs). Required for miRNA-dependent translational repression of complementary mRNAs by argonaute family proteins As scaffoldng protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (By similarity).|||The silencing domain, also known as C-terminal effector domain (CED), can act in autonomous repression, including both translational inhibition and mRNA degradation. http://togogenome.org/gene/10090:Gpr39 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1E4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane http://togogenome.org/gene/10090:Vmn1r35 ^@ http://purl.uniprot.org/uniprot/Q8R2E2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mup4 ^@ http://purl.uniprot.org/uniprot/A2ANT5|||http://purl.uniprot.org/uniprot/P11590 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Binds pheromones, likely to displace pheromones complexed to urinary MUPs and transport them to the vomeronasal organ (VNO) where they associate with their neuronal receptor(s). MUP4 is highly specific for the male mouse pheromone 2-sec-butyl-4,5-dihydrothiazole (SBT).|||Expressed in lacrimal gland, parotid gland, sublingual gland, nasal mucus, and vomeronasal organ.|||Secreted http://togogenome.org/gene/10090:Car12 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0W4|||http://purl.uniprot.org/uniprot/Q8CI85|||http://purl.uniprot.org/uniprot/Q8K2J1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-carbonic anhydrase family.|||Cell membrane|||Homodimer.|||Inhibited by acetazolamide.|||Membrane|||Reversible hydration of carbon dioxide. http://togogenome.org/gene/10090:Gatad2b ^@ http://purl.uniprot.org/uniprot/Q8VHR5 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Both CR1 and CR2 regions are required for speckled nuclear localization.|||Chromosome|||Homooligomer. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with MBD2; this is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin. Interacts with MBD3. Component of the MeCP1 histone deacetylase complex. Interacts with histone tails, including that of histones H2A, H2B, H3 and H4. Interacts with ERCC6.|||May be due to intron retention.|||Nucleus|||Nucleus speckle|||Transcriptional repressor. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2A. Targets MBD3 to discrete loci in the nucleus. May play a role in synapse development. http://togogenome.org/gene/10090:Ebpl ^@ http://purl.uniprot.org/uniprot/Q9D0P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EBP family.|||Does not possess sterol isomerase activity and does not bind sigma ligands.|||Endoplasmic reticulum membrane|||Homodimer. http://togogenome.org/gene/10090:Tmem131l ^@ http://purl.uniprot.org/uniprot/A0A0B4J1F5|||http://purl.uniprot.org/uniprot/Q3U3D7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM131 family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||In its membrane-associated form, antagonizes canonical Wnt signaling by triggering lysosome-dependent degradation of Wnt-activated LRP6. Regulates thymocyte proliferation. http://togogenome.org/gene/10090:Tmprss11e ^@ http://purl.uniprot.org/uniprot/Q5S248 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Expressed in epidermal, oral and male reproductive tissues.|||Forms a heterodimer with SERPINA5 and SERPINE1.|||Inhibited by SERPINA5.|||N-glycosylated.|||Secreted|||Serine protease which possesses both gelatinolytic and caseinolytic activities. Shows a preference for Arg in the P1 position. http://togogenome.org/gene/10090:Or10q12 ^@ http://purl.uniprot.org/uniprot/Q8VEZ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc43a3 ^@ http://purl.uniprot.org/uniprot/A2AVZ9 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the SLC43A transporter (TC 2.A.1.44) family.|||High expression in the heart, followed by the lung, liver, spleen and kidney (PubMed:11704567). Highly expressed in adipose tissue (PubMed:32217606).|||Highly expressed in the early embryo. High expression at embryonic day 7 and later in the fetal liver, lung, placenta and kidney.|||Induced during the differentiation of adipocytes.|||Sodium-independent purine-selective nucleobase transporter which mediates the equilibrative transport of extracellular purine nucleobases such as adenine, guanine and hypoxanthine (By similarity). May regulate fatty acid (FA) transport in adipocytes, acting as a positive regulator of FA efflux and as a negative regulator of FA uptake (PubMed:32217606). http://togogenome.org/gene/10090:Amdhd2 ^@ http://purl.uniprot.org/uniprot/Q8JZV7 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the metallo-dependent hydrolases superfamily. NagA family.|||Binds 1 divalent metal cation per subunit.|||Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway. http://togogenome.org/gene/10090:H2-M10.5 ^@ http://purl.uniprot.org/uniprot/Q85ZW7|||http://purl.uniprot.org/uniprot/Q860W5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Fhip2a ^@ http://purl.uniprot.org/uniprot/Q8CDM8 ^@ Function|||Similarity ^@ Belongs to the FHIP family.|||May be required for proper functioning of the nervous system. http://togogenome.org/gene/10090:Zfp467 ^@ http://purl.uniprot.org/uniprot/Q8JZL0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Down-regulated by CTF1, PTH and OSM.|||Interacts with STAT3. Enhances STAT3 activity by keeping it in the nucleus.|||Nucleus|||Transcription factor that promotes adipocyte differentiation and suppresses osteoblast differentiation in the bone marrow. Enhances the osteoclast-supporting ability of stromal cells. Binds with STAT3 the consensus sequence 5'-CTTCTGGGAAGA-3' of the acute phase response element (APRE). Transactivates several promoters including FOS, OSM and PPARG. Recruits a histone deacetylase complex. http://togogenome.org/gene/10090:Asl ^@ http://purl.uniprot.org/uniprot/Q91YI0 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Acetylation modifies enzyme activity in response to alterations of extracellular nutrient availability. Acetylation increased with trichostin A (TSA) or with nicotinamide (NAM). Glucose increases acetylation by about a factor of 3 with decreasing enzyme activity. Acetylation on Lys-288 is decreased on the addition of extra amino acids resulting in activation of enzyme activity.|||Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.|||Catalyzes the reversible cleavage of L-argininosuccinate to fumarate and L-arginine, an intermediate step reaction in the urea cycle mostly providing for hepatic nitrogen detoxification into excretable urea as well as de novo L-arginine synthesis in nonhepatic tissues (By similarity). Essential regulator of intracellular and extracellular L-arginine pools. As part of citrulline-nitric oxide cycle, forms tissue-specific multiprotein complexes with argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-arginine synthesis while channeling extracellular L-arginine to nitric oxide synthesis pathway (PubMed:22081021).|||Enzyme activity is regulated by acetylation.|||Expressed in lung and brain (at protein level).|||Homotetramer (By similarity). Forms tissue-specific complexes with ASS1, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or NOS3; the complex maintenance is independent of ASL catalytic function (PubMed:22081021). http://togogenome.org/gene/10090:Rap2a ^@ http://purl.uniprot.org/uniprot/Q80ZJ1 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by the guanine nucleotide-exchange factors RAPGEF3 and RAPGEF4 in a cAMP-dependent manner. Nucleotide exchange is also specifically stimulated by RAPGEF5, RASGEF1A and RASGEF1B (By similarity).|||Belongs to the small GTPase superfamily. Ras family.|||Expressed in granular layer of the cerebellum, forebrain, striatum, layer V of the cortex, olfactory cortex, tubercules, subthalamic and hippocampus, particularly in the CA2 region, to a lesser extent in the CA1 region and the external layer of the dentate gyrus. Expressed in neurons.|||Interacts with PLCE1. Interacts with ARHGAP29, SGSM1, SGSM2 and SGSM3. Interacts (GTP-bound form preferentially) with MAP4K4. Interacts with MINK1. Interacts with cytoskeletal actin (By similarity). Interacts (GTP-bound form) with RUNDC3A. Interacts (GTP-bound form preferentially) with TNIK (via the CNH domain); the interaction is direct and recruits RAP2A to the E3 ubiquitin ligase NEDD4. Interacts with RGS14; the interaction is GTP-dependent.|||Midbody|||Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK.|||Recycling endosome membrane|||Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. In its active form interacts with and regulates several effectors including MAP4K4, MINK1 and TNIK. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it is part of several signaling cascades and may regulate cytoskeletal rearrangements, cell migration, cell adhesion and cell spreading.|||The effector domain mediates the interaction with RUNDC3A.|||Transgenic mice expressing a constitutively active form of Rap2a display impaired spatial learning and defective extinction of contextual fear.|||Ubiquitinated; undergoes 'Lys-63' monoubiquitination and diubiquitination by NEDD4. Multiple lysine residues are probably modified. Ubiquitination requires TNIK, prevents interaction with effectors and inactivates RAP2A. http://togogenome.org/gene/10090:Cdc25b ^@ http://purl.uniprot.org/uniprot/P30306|||http://purl.uniprot.org/uniprot/Q3U535|||http://purl.uniprot.org/uniprot/Q9DBN8 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MPI phosphatase family.|||Detected at the one-cell stage followed by a decrease in signal intensity at the two-cell stage. Detectable at higher level in the four-cell stage and expressed through the eight-cell, 16-cell and morula stages. Maximal expression at the blastocyst stage.|||Expressed predominantly in spleen, lung, heart, brain, intestine, and muscle.|||Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.|||Interacts with MAPK14 and 14-3-3 proteins.|||Phosphorylated by BRSK1 in vitro. Phosphorylated by CHEK1, which inhibits the activity of this protein. Phosphorylation at Ser-351 by AURKA might locally participate in the control of the onset of mitosis. Phosphorylation by MELK at Ser-167 promotes localization to the centrosome and the spindle poles during mitosis. Phosphorylation at Ser-321 and Ser-372 by MAPK14 is required for binding to 14-3-3 proteins (By similarity).|||Stimulated by B-type cyclins.|||Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Directly dephosphorylates CDK1 and stimulates its kinase activity (By similarity).|||centrosome|||spindle pole http://togogenome.org/gene/10090:Slc9a2 ^@ http://purl.uniprot.org/uniprot/Q3ZAS0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Expressed in the colonic epithelium predominantly in the cryptal region. Maximally expressed in the luminal membrane near the crypt base and in the middle of the crypt (at protein level) (PubMed:14962844). Expressed in gastric epithelium (at protein level) (PubMed:21900251).|||In colonic crypts activated by low pHi, hyperosmolarity, and an increase in intracellular cAMP levels.|||Interacts with CHP1 and CHP2.|||Plasma membrane Na(+)/H(+) antiporter (PubMed:14962844, PubMed:16690903). Mediates the electroneutral exchange of intracellular H(+) ions for extracellular Na(+) (PubMed:14962844). Major apical Na(+)/H(+) exchanger in the base of the colonic crypt (PubMed:14962844, PubMed:16690903). Controls in the colonic crypt intracellular pH (pHi) to direct colonic epithelial cell differentiation into the absorptive enterocyte lineage at the expense of the secretory lineage (PubMed:34985202, PubMed:14962844).|||SLC9A2 null mice do not develop diarrhea, have no changes in quantitated intestinal Na(+) absorption, however mice develop a sharp reduction in the number of gastric parietal and zymogenic cells associated with a loss of net acid secretion in adult but not in juvenile mice (PubMed:9502765, PubMed:11099134). SLC9A2 null mice also exhibited reduced recovery from laser-induced ulceration of the stomach (PubMed:21900251). Double-knockout of SLC9A2 and SLC9A3 are not significantly different than the SLC9A3-deficient alone in diarrhea, intestinal Na(+) absorption, or reduced life expectancy (PubMed:11705743). Steady-state pH intracellular is significantly altered along the colonic crypt axis in deficicent mice (PubMed:34985202). http://togogenome.org/gene/10090:Ppp1r2 ^@ http://purl.uniprot.org/uniprot/Q9DCL8 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the protein phosphatase inhibitor 2 family.|||Heterodimer with PP1.|||Inhibitor of protein-phosphatase 1.|||Phosphorylation on Ser-45 by ATM activates PP1 by dissociating the PP1-PPP1R2 complex. Phosphorylation on Thr-74 by GSK3 activates PP1 by dissociating the PP1-PPP1R2 complex. http://togogenome.org/gene/10090:Rps23 ^@ http://purl.uniprot.org/uniprot/P62267 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS12 family.|||Component of the 40S small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:36517592). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:36517592). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:36517592). Plays an important role in translational accuracy (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Hydroxylation at Pro-62 affects translation termination efficiency.|||Rough endoplasmic reticulum|||cytosol|||nucleolus http://togogenome.org/gene/10090:1110032F04Rik ^@ http://purl.uniprot.org/uniprot/E9Q0B3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cldnd2 ^@ http://purl.uniprot.org/uniprot/Q9D9H2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family.|||Membrane http://togogenome.org/gene/10090:Ifi30 ^@ http://purl.uniprot.org/uniprot/Q9ESY9 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GILT family.|||Both precursor form and mature form have thiol reductase activity.|||Dimer; disulfide-linked.|||Lysosomal thiol reductase that can reduce protein disulfide bonds. May facilitate the complete unfolding of proteins destined for lysosomal degradation. Plays an important role in antigen processing. Facilitates the generation of MHC class II-restricted epitodes from disulfide bond-containing antigen by the endocytic reduction of disulfide bonds. Facilitates also MHC class I-restricted recognition of exogenous antigens containing disulfide bonds by CD8+ T-cells or crosspresentation.|||Lysosome|||Mice lacking GILT are deficient in generating major histocompatibility complex class-II-restricted CD4(+) T-cell responses to protein antigens that contain disulfide bonds. Mice are partially protected from Listeria monocytogenes infection, they exhibit reduced bacterial replication in spleen and liver. Bacterial escape from the phagosome is impaired in the macrophages of these mice.|||N-glycosylated. Sugar chains contain mannose-6-phosphate (By similarity).|||Secreted|||Synthesized as a 35 kDa precursor which is then processed into the mature 30 kDa form via cleavage of N-terminal and C-terminal propeptides. Processing of the precursor is mediated by multiple lysosomal proteases (By similarity). http://togogenome.org/gene/10090:Hrnr ^@ http://purl.uniprot.org/uniprot/Q8BLX1 ^@ Similarity ^@ Belongs to the S-100 family. http://togogenome.org/gene/10090:Hspg2 ^@ http://purl.uniprot.org/uniprot/E9PZ16|||http://purl.uniprot.org/uniprot/Q05793|||http://purl.uniprot.org/uniprot/Q3UHH3|||http://purl.uniprot.org/uniprot/Q52KG8 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ About 40% of perlecan null mice die at 10.5 dpc, the rest die just after birth. Embryonic percelan-null mice exhibit cardiac abnormalities including mechanical instability in the early stages of development (10.5 dpc) with lower amounts of critical basement membrane components, collagen IV and lamanins. Basement membranes are absent in cardiomyocytes whereas adherens junctions formed and matured around 9.5 dpc. Mice also have skeletal dysplasia characterized by micromelia with broad and bowed long bones, narrow thorax and craniofacial abnormalities. Cartilage matrix contains reduced and disorganized collagen fibrils and glycosaminoglycans. In cartilage, proliferation of chondrocytes was reduced and the prehypertrophic zone was diminished.|||Anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6 (By similarity).|||Has a strong tendency to aggregate in dimers or stellate structures. Interacts with other basement membrane components such as laminin, prolargin and collagen type IV. Interacts with COL13A1, FGFBP1 and VWA1. Interacts (via C-terminus) with ECM1 (via C-terminus) (By similarity).|||Has anti-angiogenic properties that require binding of calcium ions for full activity.|||Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||O-glycosylated. Contains three heparan sulfate chains. Also contains chondroitin sulfate.|||Proteolytic processing produces the C-terminal angiogenic peptide, endorepellin. This peptide can be further processed to produce the LG3 peptide (By similarity).|||Secreted|||basement membrane http://togogenome.org/gene/10090:Fam219b ^@ http://purl.uniprot.org/uniprot/Q14DQ1 ^@ Similarity ^@ Belongs to the FAM219 family. http://togogenome.org/gene/10090:Gm3776 ^@ http://purl.uniprot.org/uniprot/Q6P8Q0 ^@ Similarity ^@ Belongs to the GST superfamily. Alpha family. http://togogenome.org/gene/10090:Phf20 ^@ http://purl.uniprot.org/uniprot/Q8BLG0 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Contributes to methyllysine-dependent p53/TP53 stabilization and up-regulation after DNA damage (By similarity). Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. Not required for maintaining the global histone H4 'Lys-16' acetylation (H4K16ac) levels or locus specific histone acetylation, but instead works downstream in transcriptional regulation of MOF target genes. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues.|||Homodimer; disulfide-linked. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (By similarity).|||Incomplete sequence.|||Mice die shortly after birth and display a wide variety of phenotypes within the skeletal and hematopoietic systems.|||Nucleus|||The Tudor domain 1 doesn't bind dimethyl-lysine residues, due to an atypical and occluded aromatic cage.|||The Tudor domain 2 mediates reading of dimethyl-lysine residues.|||Ubiquitinated by TRIM26; leading to proteasomal degradation. http://togogenome.org/gene/10090:Garin1a ^@ http://purl.uniprot.org/uniprot/B2RXB0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GARIN family.|||Expressed from day 21, around when spermiogenesis occurs (PubMed:34714330). Expression dramatically increases at the mid-round spermatid stage (steps 4-6) (PubMed:34714330).|||Expressed in testis (at protein level).|||Golgi apparatus|||Interacts (via N-terminus) with RAB2B (in GTP-bound form).|||Mutant male fertility is significantly impaired compared with that of the controls (PubMed:34714330). Spermatozoa from mutant mice showed abnormal head shapes with an abnormal acrosome morphology (PubMed:34714330).|||RAB2B effector protein required for accurate acrosome formation and normal male fertility. http://togogenome.org/gene/10090:Mtus2 ^@ http://purl.uniprot.org/uniprot/Q3UHD3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aberrant splicing.|||Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules. May regulate the dynamics of microtubules at their growing distal tip (By similarity).|||Expressed in heart from early embryonic development onwards. Later during embryonic development, expressed in brain and nervous system, in limb buds and in the epithelium lining the bronchia of the lung. Detected in adult brain, heart and eye, but not detected in other adult tissues examined.|||Homodimer. Interacts with KIF2C and MAPRE1; the interaction is direct and probably targets MTUS2 and KIF2C to microtubules (By similarity).|||In the C-terminal section; belongs to the MTUS1 family.|||cytoskeleton http://togogenome.org/gene/10090:Appbp2 ^@ http://purl.uniprot.org/uniprot/Q9DAX9 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter APPBP2. Interacts with APP; APP interaction inhibits the E3 ubiquitin-protein ligase activity of the CRL2(APPBP2) complex.|||E3 ubiquitin-protein ligase activity of the CRL2(APPBP2) complex is inhibited by APP.|||Membrane|||Nucleus|||Rapidly degraded by the proteasome upon overexpression of a C-terminal fragment of APP.|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(APPBP2) complex specifically recognizes proteins with a -Arg-Xaa-Xaa-Gly degron at the C-terminus, leading to their ubiquitination and degradation. The CRL2(APPBP2) complex mediates ubiquitination and degradation of truncated SELENOV selenoproteins produced by failed UGA/Sec decoding, which end with a -Arg-Xaa-Xaa-Gly degron. May play a role in intracellular protein transport: may be involved in the translocation of APP along microtubules toward the cell surface.|||cytoskeleton http://togogenome.org/gene/10090:Mlh1 ^@ http://purl.uniprot.org/uniprot/Q9JK91 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA mismatch repair MutL/HexB family.|||Chromosome|||Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer of MLH1 and PMS2 (MutL alpha), MLH1 and PMS1 (MutL beta) or MLH1 and MLH3 (MutL gamma). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MCM9; the interaction recruits MLH1 to chromatin. Interacts with MCM8. Interacts with PMS2. Interacts with MBD4. Interacts with EXO1. Interacts with MTMR15/FAN1.|||Heterodimerizes with Pms2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (Msh2-Msh6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of Pms2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (Mlh1-Pms2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with Mlh3 to form MutL gamma which plays a role in meiosis (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ercc5 ^@ http://purl.uniprot.org/uniprot/E9QM61|||http://purl.uniprot.org/uniprot/Q3UV64 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.|||Nucleus http://togogenome.org/gene/10090:Spred2 ^@ http://purl.uniprot.org/uniprot/Q924S7 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Homodimer and heterodimer (By similarity). Able to interact with SPRED1 to form heterodimers (By similarity). Interacts with RAS (PubMed:11493923). May interact with ZDHHC13 (via ANK repeats) and ZDHHC17 (via ANK repeats) (PubMed:28882895). Interacts with TESK1 (PubMed:17974561). Interacts with NF1 (By similarity).|||Negatively regulates Ras signaling pathways and downstream activation of MAP kinases (PubMed:11493923). Recruits and translocates NF1 to the cell membrane, thereby enabling NF1-dependent hydrolysis of active GTP-bound Ras to inactive GDP-bound Ras (By similarity). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (PubMed:29501879). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (PubMed:25576668).|||Phosphorylated on serine and threonine residues. Phosphorylated on tyrosine. Phosphorylation of Tyr-224 and Tyr-227 are required for ubiquitination.|||Predominantly expressed in lung, liver and testis. In testis, it is specially found in mature spermatids projecting into the lumen of the seminiferous. Strongly expressed in glandular epithelia. Also expressed in embryonic tissues such as heart, lung, liver and brain.|||SPRED2 knockout results in a dwarf phenotype characterized by reduced growth and body weight, shorter tibia length, and narrower growth plates as compared with wild-type mice. Mutant animals regularly develop kyphosis and scoliosis, and show craniofacial defects, splenomegaly, and cardiac hypertrophy with arrhythmias.|||Ubiquitinated; leading to degradation by the proteasome.|||secretory vesicle membrane http://togogenome.org/gene/10090:D11Wsu47e ^@ http://purl.uniprot.org/uniprot/Q6PIX9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Nrg1 ^@ http://purl.uniprot.org/uniprot/A0A140LHZ9|||http://purl.uniprot.org/uniprot/A0A5F8MPT8|||http://purl.uniprot.org/uniprot/Q6DR99 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the neuregulin family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Secreted http://togogenome.org/gene/10090:Gipc3 ^@ http://purl.uniprot.org/uniprot/Q8R5M0 ^@ Disease Annotation|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the GIPC family.|||Defects in GIPC3 underlie the age-related hearing loss 5 (ahl5) and juvenile audiogenic monogenic seizure (jams1) phenotypes. Ahl5 mice show irregular structure of the stereocilia bundle of outer and inner hair cells, late-onset degeneration of the organ of Corti. The spiral ganglion exhibits a severe loss of neurons.|||Expressed in adult lung, brain and testis. In the inner ear, it is expressed in the inner and outer hair cells of the organ of Corti. Also expressed in cochlear spiral ganglion neurons.|||Required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion. http://togogenome.org/gene/10090:Cts7 ^@ http://purl.uniprot.org/uniprot/Q91ZF2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Endosome|||Expressed in adult but not in embryo. Expressed in the placenta from early post-implantation (5.5 dpc) onwards. After 9.5 dpc expression declines.|||Expressed in placenta. Expressed in parietal and spiral artery-associated trophoblast giant cells, most abundantly during the phase of trophoblast invasion. From 14.5 dpc onwards, expressed at lower levels in labyrinth trophoblast cells. Expressed in trophoblast stem cells. Expressed in heart, liver and testis.|||Golgi apparatus|||Involved in trophoblast cell proliferation and differentiation probably by affecting mitotic cell cycle progression. Proteolytic activity and nuclear localization are essential for its role in cell cycle progression.|||Lysosome|||Nucleus|||extracellular space|||perinuclear region http://togogenome.org/gene/10090:Pip5kl1 ^@ http://purl.uniprot.org/uniprot/Q6U7H8 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in brain and testis, relatively to heart, spleen, lung, liver, skeletal muscle and kidney.|||In spite of its similarity to other phosphatidylinositol kinases, lacks intrinsic lipid kinase activity.|||Interacts with type I phosphatidylinositol 4-phosphate 5-kinases, including PIP5K1A and PIP5K1B.|||May act as a scaffold to localize and regulate type I phosphatidylinositol 4-phosphate 5-kinases to specific compartments within the cell, where they generate PI(4,5)P2 for actin nucleation, signaling and scaffold protein recruitment and conversion to PI(3,4,5)P3.|||Membrane http://togogenome.org/gene/10090:Gba2 ^@ http://purl.uniprot.org/uniprot/Q69ZF3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the non-lysosomal glucosylceramidase family.|||Endoplasmic reticulum membrane|||Enzymatic activity is dependent on membrane association and requires the presence of lipids (PubMed:23250757). Inhibited by N-(adamantanemethyloxypentyl)-deoxynojirimycin/AMP-DNM (PubMed:26724485). Inhibited by its product sphingosine/N-acylsphing-4-enine in a feedback loop (PubMed:28258214). Also inhibited by other non-acetylated sphingoid bases and their derivatives but not by sphingosine-1-phosphate and complex sphingolipids (PubMed:28258214).|||Golgi apparatus membrane|||Homozygous knockout mice display an accumulation of glucosylceramides in testis, brain and liver (PubMed:17080196). The accumulation of glucosylceramides in Sertoli cells alters sperm shape and males exhibit impaired fertility (PubMed:17080196). Despite the bile acid glucosidase and transferase activities measured in vitro, bile acid metabolism is normal in knockout mice (PubMed:17080196). No obvious neurological symptoms, organomegaly or lifespan alteration are observed (PubMed:17080196). Cholesterol metabolism and protein glycosylation are also normal in these mice (PubMed:17080196).|||Non-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) to free glucose and ceramides (such as N-acylsphing-4-enine) (PubMed:17080196, PubMed:23250757). GlcCers are membrane glycosphingolipids that have a wide intracellular distribution (PubMed:23250757). They are the main precursors of more complex glycosphingolipids that play a role in cellular growth, differentiation, adhesion, signaling, cytoskeletal dynamics and membrane properties (PubMed:25803043). Also involved in the transglucosylation of cholesterol, transferring glucose from GlcCer, thereby modifying its water solubility and biological properties (PubMed:26724485, PubMed:32144204). Under specific conditions, may catalyze the reverse reaction, transferring glucose from cholesteryl-3-beta-D-glucoside to ceramide (such as N-acylsphing-4-enine) (PubMed:26724485, PubMed:32144204). May play a role in the metabolism of bile acids (PubMed:17080196). Able to hydrolyze bile acid 3-O-glucosides as well as to produce bile acid-glucose conjugates thanks to a bile acid glucosyl transferase activity (PubMed:17080196). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as galactosyl transfer between GalCers and cholesterol in vitro with lower activity compared with their activity against GlcCers (PubMed:32144204).|||Widely expressed at low level (PubMed:17080196). Highly expressed in testis and brain (PubMed:17080196). Ubiquitously expressed in the brain (at protein level) (PubMed:23250757). Expressed by Sertoli cells (at protein level) (PubMed:17080196). http://togogenome.org/gene/10090:Kif5a ^@ http://purl.uniprot.org/uniprot/P33175|||http://purl.uniprot.org/uniprot/Q3US62 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin subfamily.|||Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.|||Death shortly after birth. Neuron-specific deletion within the first 3 weeks after birth is lethal in 75% of animals. Surviving animals show accumulation of neurofilament proteins in neuronal soma, age-dependent sensory neuron degeneration, loss of large caliber axons, and hind limb paralysis with a stronger effect on sensory neurons compared with motor neurons.|||Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL) (PubMed:12682084). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 proteins in neurons (PubMed:21976701). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity).|||Oligomer composed of two heavy chains and two light chains. Interacts with GRIP1 (PubMed:11986669). Interacts with FMR1 (via C-terminus); this interaction is increased in a mGluR-dependent manner (PubMed:18539120). Interacts with BORCS5 (By similarity). Interacts with ZFYVE27 (PubMed:21976701, PubMed:24251978). Interacts with VAPA, VAPB, SURF4, RAB11A (GDP-bound form), RAB11B (GDP-bound form) and RTN3 in a ZFYVE27-dependent manner (PubMed:21976701). Interacts with BICD2 (By similarity). Interacts with DTNB (PubMed:14600269).|||Perikaryon|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Pilra ^@ http://purl.uniprot.org/uniprot/Q2YFS3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. PTPN6 seems to bind predominantly to the first ITIM motif (By similarity).|||Interacts with CD99.|||Membrane|||Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. Receptor for CD99 and PIANP.|||Phosphorylated on tyrosine residues. http://togogenome.org/gene/10090:Gpt2 ^@ http://purl.uniprot.org/uniprot/Q8BGT5 ^@ Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family. Alanine aminotransferase subfamily.|||Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.|||Homodimer.|||May be responsible for increased ALT activity in hepatic steatosis.|||Specifically induced in fatty liver. Highly expressed in muscle, liver and white adipose tissue. Moderately expressed in brain and kidney and expressed at low levels in the heart. http://togogenome.org/gene/10090:Dbndd2 ^@ http://purl.uniprot.org/uniprot/Q330P7|||http://purl.uniprot.org/uniprot/Q9CRD4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the dysbindin family.|||May modulate the activity of casein kinase-1. Inhibits CSNK1D autophosphorylation (in vitro) (By similarity).|||Monomer. Interacts with CSNK1D and CSNK1E (By similarity). http://togogenome.org/gene/10090:Pcdhgb6 ^@ http://purl.uniprot.org/uniprot/Q91XX4 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Napb ^@ http://purl.uniprot.org/uniprot/P28663 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNAP family.|||Cerebral cortex, cerebellar cortex, hippocampus, and dentate gyrus, weakly expressed in the putamen, the thalamus and the brain stem.|||Interacts with PRKCABP, and disrupts the interaction between GRIA2 and PRKCABP, leading to the internalization of GRIA2.|||Membrane|||Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus. http://togogenome.org/gene/10090:Tbc1d8 ^@ http://purl.uniprot.org/uniprot/Q9Z1A9 ^@ Domain|||Function ^@ May act as a GTPase-activating protein for Rab family protein(s).|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site. http://togogenome.org/gene/10090:Asb16 ^@ http://purl.uniprot.org/uniprot/Q8VHS5 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Perm1 ^@ http://purl.uniprot.org/uniprot/Q149B8 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By PPARGC1A, PPARGC1B, ESRRA, ESRRB and ESRRG.|||Cytoplasm|||Highly expressed in skeletal muscles and heart with lower levels in brown adipose tissue (at protein level). Muscle-specific expression is increased by endurance exercise.|||Nucleus|||Regulates the expression of selective PPARGC1A/B and ESRRA/B/G target genes with roles in glucose and lipid metabolism, energy transfer, contractile function, muscle mitochondrial biogenesis and oxidative capacity. Required for the efficient induction of MT-CO2, MT-CO3, COX4I1, TFB1M, TFB2M, POLRMT and SIRT3 by PPARGC1A. Positively regulates the PPARGC1A/ESRRG-induced expression of CKMT2, TNNI3 and SLC2A4 and negatively regulates the PPARGC1A/ESRRG-induced expression of PDK4. http://togogenome.org/gene/10090:Lce1h ^@ http://purl.uniprot.org/uniprot/Q9D6R3 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Trim28 ^@ http://purl.uniprot.org/uniprot/Q62318 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by SIRT6, promoting TRIM28/KAP1 interaction with CBX5, thereby contributing to the packaging of LINE-1 retrotransposon elements into transcriptionally repressive heterochromatin.|||ATM-induced phosphorylation on Ser-824 represses sumoylation leading to the de-repression of expression of a subset of genes involved in cell cycle control and apoptosis in response to genotoxic stress. Dephosphorylation by the phosphatases, PPP1CA and PP1CB forms, allows sumoylation and expression of TRIM28 target genes.|||Auto-ubiquitinated; enhanced by MAGEA2 and MAGEC2.|||Belongs to the TRIM/RBCC family.|||Citrullinated by PADI4.|||Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.|||Embryonic lethal with arrest at stage E5.5. Gastrulation fails and expression of the critical mesoderm differentiation factor T/brachyury is lost.|||Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs) (PubMed:20164836, PubMed:22110054, PubMed:25247314, PubMed:27658112). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also a corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteasomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:20164836). In ESCs, in collaboration with SETDB1, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (PubMed:20164836). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (By similarity). Acts as a corepressor for ZFP568 (PubMed:22110054, PubMed:27658112).|||Nucleus|||Oligomer; the RBCC domain homotrimerizes and interacts with one molecule of KRAB to form the KRAB-KAP1 corepressor complex. Interacts with SETX (By similarity). Binding to a KRAB domain is an absolute requirement for silencing gene expression. Interacts with a number of KRAB-ZFP proteins including ZNF10, ZFP53, ZFP68, ZNF382 and ZNF256. Interacts with NCOR1, NR3C1 and CHD3. Interacts with CEBPB (via the RING-type and PHD-type zinc fingers). Interacts with CBX5 (via the PxVxL motif); the interaction occurs in interphase nuclei and competes for binding POGZ (PubMed:10562550, PubMed:10330177, PubMed:25247314). Interacts with POGZ; the interaction competes for interaction with CBX5. Interacts with SETDB1; the interaction is enhanced by KAP1 sumoylation, stimulates SETDB1 histone methyltransferase activity and gene silencing. Interacts (via the PHD-type zinc finger) with UBE2I; the interaction is required for sumoylation and repressor activity. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor and DNA damage responses. Interacts directly with ERBB4; the interaction represses ERBB4-mediated transcription activity. Interacts with MDM2; the interaction contributes to p53/TP53 inactivation. Component of the TRIM28/KAP1-MDM2-p53/TP53; involved in regulating p53/TP53 stabilization and activity. Interacts (via the leucine zipper alpha helical coiled-coil) with E2F1 (central region); the interaction inhibits E2F1 acetylation and transcriptional activity. Interacts with PPP1CA; the interaction dephosphorylates TRIM28 at Ser-824 and forms a complex at the p21 promoter site. Interacts with PPP1CB; the interaction is weak but is increased on dephosphorylation at Ser-824. Interacts with CEBPB and NR3C1. Interacts with CBX5 (via the PxVxL motif); the interaction occurs in interphase nuclei and competes for binding POGZ. Component of a ternary complex that includes TRIM28, a HP1 protein (CBX1, CBX3 OR CBX5), a KRAB domain-containing protein, and DNA. Interacts with SMARCAD1. Interacts with, and sumoylates IRF7. Interacts with MAGEC2. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts (via the RBCC domain) with KOX1 (via the KRAB domain), ZNF268 (via the KRAB domain) and ZNF300 (via the KRAB domain); the interactions increase KOX1, ZNF268 and ZNF300 nuclear localization activities. Interacts with AICDA. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex. Interacts with NR4A3; the interactions potentiates NR4A3 activity on NurRE promoter (PubMed:19321449). Interacts (unphosphorylated or phosphorylated form) with ZBTB1 (via BTB domain) (By similarity). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1. Interacts with ATRX. Forms a complex with ATRX, SETDB1 and ZNF274 (By similarity). Interacts with ZFP568; the interaction mediates ZFP568 transcriptional repression activity (PubMed:22110054, PubMed:27658112). Interacts with RRP1B (By similarity). Interacts with CRY1 (PubMed:27123980). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). Interacts with CYREN (via XLF motif) (PubMed:30017584). Interacts with TRIM17; this interaction prevents TRIM28 activity (By similarity). Interacts with ZNF746 (By similarity).|||Sumoylation/desumoylation events regulate TRIM28-mediated transcriptional repression. Sumoylation is required for interaction with CHD3 and SETDB1 and the corepressor activity. Represses and is repressed by Ser-824 phosphorylation. Enhances the TRIM28 corepressor activity, inhibiting transcriptional activity of a number of genes including GADD45A and CDKN1A/p21. Lys-554, Lys-779 and Lys-804 are the major sites of sumoylation. In response to Dox-induced DNA damage, enhanced phosphorylation on Ser-824 prevents sumoylation and allows de-repression of CDKN1A/p21.|||The HP1 box is both necessary and sufficient for HP1 binding.|||The PHD-type zinc finger enhances CEBPB transcriptional activity. The PHD-type zinc finger, the HP1 box and the bromo domain, function together to assemble the machinery required for repression of KRAB domain-containing proteins. Acts as an intramolecular SUMO E3 ligase for autosumoylation of bromodomain.|||The RING-finger-B Box-coiled-coil/tripartite motif (RBCC/TRIM motif) is required for interaction with the KRAB domain of KRAB-zinc finger proteins. Binds four zinc ions per molecule. The RING finger and the N-terminal of the leucine zipper alpha helical coiled-coil region of RBCC are required for oligomerization. http://togogenome.org/gene/10090:Wnt5a ^@ http://purl.uniprot.org/uniprot/P22725 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A palmitoylation site was proposed at Cys-104, but it was later shown that this cysteine is engaged in a disulfide bond.|||Belongs to the Wnt family.|||Expressed in a gradient at the caudal end of the embryo during gastrulation and later in the distal-most aspect of several structures that extend from the body such as the limbs and genital tubercle.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Homooligomer; disulfide-linked, leading to inactivation (PubMed:22726442). Interacts with PORCN (PubMed:10866835). Interacts with WLS (PubMed:19841259). Interacts with glypican GCP3 (By similarity). Interacts with PKD1 (via extracellular domain) (PubMed:27214281). Interacts with TMEM67 (By similarity).|||Glycosylation is necessary for secretion but not for activity.|||Ligand for members of the frizzled family of seven transmembrane receptors (PubMed:17117926). Can activate or inhibit canonical Wnt signaling, depending on receptor context (PubMed:16602827). In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression (PubMed:16602827). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration (PubMed:17117926). Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells (By similarity). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle (PubMed:10021340). Inhibits type II collagen expression in chondrocytes (By similarity).|||Mice display perinatal lethality and display gross morphological defects in outgrowing tissues. They are truncated caudally, displaying loss of the tail and a significant shortening of the anterior-posterior axis. The shape of the head is abnormal with truncated snout, mandible and tongue and reduced outgrowth of the external ear. Fore- and hindlimbs lack digits, the genital tubercle is missing and chondrocyte differentiation is inhibited.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT5A.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Triobp ^@ http://purl.uniprot.org/uniprot/Q99KW3 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to TRIO and F-actin (By similarity). May also interact with myosin II (By similarity). Interacts with HECTD3 (By similarity). Interacts with PJVK (PubMed:28209736). Isoform 4 forms homodimers (PubMed:31217345). Isoform 4 interacts with ANKRD24; recruiting TRIOBP isoform 4 to stereocilia rootlets (PubMed:35175278).|||Contains at least 2 actin-binding sites per coiled-coil dimer.|||Deficient mice display dysmorphic rootlets that are abnormally thin in the cuticular plate but have increased widths and lengths within stereocilia cores, and causes progressive deafness.|||Deletion of isoform 4 and isoform 5 results in an absence of stereocilia rootlets and mice are profoundly deaf. Stereocilia lacking rootlets initially have a normal appearance and are capable of mecha-notransduction but are fragile. Shortly after the onset of hearing at P16, these floppy stereocilia lacking rootlets fuse together and rapidly degenerate, followed by the death of hair cells.|||Expressed in the brain, liver, kidney, retina, and inner ear.|||Expressed in the kidney, retina, testis, and inner ear.|||Expressed in the whole embryo, brain, kidney, retina, pancreas, and inner ear.|||Isoform 1-null mice are embryonic lethal.|||May regulate actin cytoskeletal organization, cell spreading and cell contraction by directly binding and stabilizing filamentous F-actin. The localized formation of TRIOBP and TRIO complexes coordinates the amount of F-actin present in stress fibers. May also serve as a linker protein to recruit proteins required for F-actin formation and turnover.|||Midbody|||Nucleus|||Phosphorylation at Thr-445 by PLK1 ensures mitotic progression and is essential for accurate chromosome segregation. Phosphorylation at residues Thr-209 and Thr-445 by kinase NEK2A and PLK1 coordinates TERF1 translocation from telomere to spindle pole.|||Plays a pivotal role in the formation of rootlets.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 3.|||Ubiquitinated by HECTD3, leading to its degradation by the proteasome.|||centrosome|||stereocilium http://togogenome.org/gene/10090:Snx27 ^@ http://purl.uniprot.org/uniprot/Q3UHD6 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. Interacts (via the FERM-like regions) with the WASH complex. Interacts with SNX1. Interacts with CYTIP. Interacts with DGKZ. Interacts with MCC (By similarity). Interacts (via PDZ domain) with a number of target transmembrane proteins (via PDZ-binding motif): ABCC4, ADRB2, ARHGEF7, GRIA1, GRIA2, GRIN1, GRIN2A GRIN2C, KCNJ6, KCNJ9 and SLC2A1/GLUT1. Interacts (via PDZ domains) with SLC9A3; directs SLC9A3 membrane insertion from early endosomes to the plasma membrane (By similarity).|||Early endosome membrane|||Expressed in cells of hematopoietic origin.|||Growth retardation followed by lethality. Some mice die in the uterus during embryonic development. Newborn mice that survive fail to thrive and all die at different times within the first 3 weeks. The body weight of newborn is lower than wild-type mice, and the postnatal growth is severely retarded, with a clear retardation of body weight gain. The growth retardation is not only reflected in the body weight, but also in multiple organs, such as the spleen, kidney, liver, heart and intestine. Mice also show neuronal deficits in the hippocampus and cortex: despite a normal neuroanatomy, defects in synaptic function, learning and memory and a reduction in the amounts of ionotropic glutamate receptors (NMDA and AMPA receptors) are observed.|||Involved in the retrograde transport from endosome to plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins. Following internalization, endocytosed transmembrane proteins are delivered to early endosomes and recycled to the plasma membrane instead of being degraded in lysosomes. SNX27 specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C-terminus: following interaction with target transmembrane proteins, associates with the retromer complex, preventing entry into the lysosomal pathway, and promotes retromer-tubule based plasma membrane recycling. SNX27 also binds with the WASH complex. Interacts with membranes containing phosphatidylinositol-3-phosphate (PtdIns(3P)). May participate in establishment of natural killer cell polarity. Recruits CYTIP to early endosomes.|||The PDZ domain mediates binding to a subset of proteins containing a PDZ-binding motif at the C-terminus: the specificity for PDZ-binding motif is provided by the 2 residues located upstream of the canonical PDZ-binding motif. The PDZ domain also mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B).|||The PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes.|||cytosol http://togogenome.org/gene/10090:Dnaja2 ^@ http://purl.uniprot.org/uniprot/Q9QYJ0 ^@ Function|||Subcellular Location Annotation ^@ Co-chaperone of Hsc70. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro).|||Membrane http://togogenome.org/gene/10090:Or9e1 ^@ http://purl.uniprot.org/uniprot/Q5NC59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Eif1ad4 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VLT7 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Brox ^@ http://purl.uniprot.org/uniprot/Q8K2Q7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BROX family.|||Farnesylation is required for nuclear envelope localization.|||Monomer. Interacts with CHMP4B. Interacts with CHMP5: this interaction allows the recruitment of BROX to cellular membranes. Interacts with SYN2; this interaction promotes SYN2 ubiquitination and facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site.|||Nuclear envelope-associated factor that is involved in the nuclear envelope ruptures during interphase (NERDI) repair, where it is locally recruited by CHMP5 and reduces cytoskeletal stress through its action on SYN2 to help reseal the ruptured membrane.|||Nucleus membrane http://togogenome.org/gene/10090:Cdkn1c ^@ http://purl.uniprot.org/uniprot/P49919|||http://purl.uniprot.org/uniprot/Q791X1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDI family.|||Expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas and testis. High levels are seen in the placenta while low levels are seen in the liver.|||Interacts with PCNA.|||Nucleus|||Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2. Negative regulator of cell proliferation. May play a role in maintenance of the non-proliferative state throughout life. http://togogenome.org/gene/10090:Vmn1r24 ^@ http://purl.uniprot.org/uniprot/Q8R2D6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Shisal2a ^@ http://purl.uniprot.org/uniprot/A2A9G7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the shisa family.|||Membrane http://togogenome.org/gene/10090:Cnot1 ^@ http://purl.uniprot.org/uniprot/A0A1D5RMJ8|||http://purl.uniprot.org/uniprot/B7ZWL1|||http://purl.uniprot.org/uniprot/Q6ZQ08 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNOT1 family.|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits (By similarity). In the complex, interacts directly with CNOT6, CNOT6L, CNOT7 or CNOT8 (By similarity). Interacts in a ligand-dependent fashion with ESR1 and RXRA (By similarity). Interacts with NANOS2, TOB1 and ZFP36 (PubMed:20133598). Interacts with TNRC6A, TNRC6B or TNRC6C; the interactions are direct (By similarity). Interacts with YTHDF2; the interaction is direct and promotes recruitment of the CCR4-NOT complex to N6-methyladenosine (m6A)-containing mRNAs, leading to their deadenylation and subsequent degradation (PubMed:32905781). Interacts with EIF4ENIF1/4E-T (By similarity).|||Contains Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, a motif known to be important for the association with nuclear receptors.|||Cytoplasm|||Expressed in embryonic stem (ES) cells and in inner cell mass (ICM) of the blastocyst. At 8.25 dpc it is expressed in both the neuroectoderm and mesenchyme of the neural folds but not in extra-embryonic membranes (PubMed:31006510).|||Nucleus|||P-body|||Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity; prevents their differentiation towards extraembryonic trophectoderm lineages. http://togogenome.org/gene/10090:Sppl3 ^@ http://purl.uniprot.org/uniprot/Q9CUS9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase A22B family.|||Endoplasmic reticulum membrane|||Golgi apparatus|||Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane protein substrates in or close to their luminal transmembrane domain boundaries. Acts like a sheddase by mediating the proteolytic release and secretion of active site-containing ectodomains of glycan-modifiying glycosidase and glycosyltransferase enzymes such as MGAT5, B4GAT1 and B4GALT1 (PubMed:25354954, PubMed:25827571). Plays a role in the regulation of cellular glycosylation processes (PubMed:25354954). Required to link T-cell antigen receptor (TCR) and calcineurin-NFAT signaling cascades in lymphocytes by promoting the association of STIM1 and ORAI1 during store-operated calcium entry (SOCE) in a protease-independent manner (PubMed:25384971).|||Its proteolytic activity is blocked by a signal peptide peptidase (SPP) inhibitor, (ZLL)2-ketone (ZLL) or a gamma-secretase inhibitor, LY411,575.|||Membrane|||Mice are viable but display growth retardation and haematologic abnormalities (PubMed:20562862). Male are sterile (PubMed:20562862). Exhibit hyperglycosylation of cellular glycoproteins (PubMed:25354954).|||Monomer. Homodimer (By similarity). Interacts with STIM1 (via transmembrane region and SOAR/CAD domain); the interaction promotes the binding of STIM1 to ORAI1 (PubMed:25384971).|||Not glycosylated.|||The first transmembrane domain may act as a type I signal anchor. The catalytic loops is exposed toward the lumen. The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family. http://togogenome.org/gene/10090:Camk1 ^@ http://purl.uniprot.org/uniprot/Q3UY68|||http://purl.uniprot.org/uniprot/Q91YS8 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-177 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results in several fold increase in total activity. Unlike CaMK4, is unable to exhibit autonomous activity after Ca(2+)/calmodulin activation (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-673', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation. Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I (By similarity).|||Cytoplasm|||Monomer. Interacts with XPO1 (By similarity).|||Nucleus|||Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.|||Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation.|||The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.|||Ubiquitous. http://togogenome.org/gene/10090:Rln3 ^@ http://purl.uniprot.org/uniprot/Q8CHK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the insulin family.|||Heterodimer of a B chain and an A chain linked by two disulfide bonds.|||High expression in the brain localized to the pons/medulla with highest levels in pars ventromedialis of the dorsal tegmental nucleus. Significant expression is also detected in the spleen, thymus, lung, testis and ovary.|||May play a role in neuropeptide signaling processes. Ligand for LGR7, relaxin-3 receptor-1 and relaxin-3 receptor-2 (By similarity).|||Secreted http://togogenome.org/gene/10090:Or8k32 ^@ http://purl.uniprot.org/uniprot/Q8VF52 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mgmt ^@ http://purl.uniprot.org/uniprot/P26187|||http://purl.uniprot.org/uniprot/Q4VA39 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MGMT family.|||Binds 1 zinc ion.|||Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.|||Nucleus|||This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocatalyst that acts repeatedly and over many reaction cycles. http://togogenome.org/gene/10090:Tssk2 ^@ http://purl.uniprot.org/uniprot/O54863 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-174, potentially by autophosphorylation.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||First expression detected at 3.5 to 4 weeks.|||Interacts with TSSK1B (PubMed:10781952, PubMed:18367677). Interacts with HSP90; this interaction stabilizes TSSK2 (PubMed:23599433).|||Male mice lacking Tssk1b and Tssk2 are sterile due to haploinsufficiency. chimeras show failure to form elongated spermatids, apoptosis of spermatocytes and spermatids, and the appearance of numerous round cells in the epididymal lumen. Elongating spermatids possess a collapsed mitochondrial sheath.|||Mg(2+) and Mn(2+) were both present in the kinase buffer but Mg(2+) is likely to be the in vivo cofactor.|||Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates 'Ser-281' of TSKS and SPAG16. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body.|||Testis-specific. Expressed only in the spermatids postmeiotically at the final stages of cytodifferentiation in the seminiferous tubules (at protein level). Not detected in released sperms in the lumen of the seminiferous tubules. Also present in the epididymal sperm (at protein level).|||Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation.|||acrosome|||centriole http://togogenome.org/gene/10090:Dynlt1c ^@ http://purl.uniprot.org/uniprot/P51807 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia (By similarity). May also be a accessory component of axonemal dynein. Plays an important role in male germ cell development and function. Candidate for involvement in male sterility.|||Belongs to the dynein light chain Tctex-type family.|||Cytoplasm|||First abundantly expressed at the pachytene stage of meiosis and persists throughout spermatogenesis.|||Golgi apparatus|||High level in testis (germ cell-specific). Expressed in sperm (at protein level). 200-fold lower in liver, brain, heart, spleen, and kidney. Levels in thymus and two embryonal carcinoma cell lines were several-fold higher than this low constitutive level.|||Homodimer (Probable). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. DYNLT1 and DYNLT3 compete for association with dynein IC (DYNC1I1 or DYNC1I2). Self-associates. Interacts with RHO (By similarity). Interacts with DYNC1I1 and DYNC1I2. Interacts with DOC2A, DOC2B and SCN10A. Interacts with PVR. Interacts with SVIL isoform 2. Interacts with GNB1; the interaction occurs in presence of guanine nucleotide-binding protein G(T) subunit gamma; the interaction diminishes the association of DYNLT1 with dynein IC (DYNC1I1 or DYNC1I2). Interacts with GNB2, GNB3 and GNB5; the interactions occur in presence of guanine nucleotide-binding protein G(T) subunit gamma. Interacts with ACVR2B and ARHGEF2 (By similarity). Interacts with DNAI4 (PubMed:30060180).|||Phosphorylated by BMPR2. The phosphorylation status is proposed to regulate the association with the cytoplasmic dynein complex and may have role in cytoplasmic dynein cargo release (By similarity).|||Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling. Involved in the regulation of mitotic spindle orientation.|||spindle http://togogenome.org/gene/10090:Nckipsd ^@ http://purl.uniprot.org/uniprot/Q9ESJ4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with the intermediate filaments, vimentin and desmin (By similarity). Binds the first and third SH3 domains of NCK (By similarity). Binds the proline-rich domains of N-WASP through its SH3 domain. Similarly, binds diaphanous protein homolog 1 (DRF1) (By similarity). Binds the SH3 domains of GRB2 through its proline-rich domains. Interacts with FASLG (By similarity).|||Has an important role in stress fiber formation induced by active diaphanous protein homolog 1 (DRF1) (By similarity). Induces microspike formation, in vivo. In vitro, stimulates N-WASP-induced ARP2/3 complex activation in the absence of CDC42. May play an important role in the maintenance of sarcomere and/or in the assembly of myofibrils into sarcomeres. Implicated in regulation of actin polymerization and cell adhesion.|||Nucleus http://togogenome.org/gene/10090:Vps8 ^@ http://purl.uniprot.org/uniprot/D3YUP0|||http://purl.uniprot.org/uniprot/Q0P5W1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the VPS8 family.|||Interacts with RAB5C (PubMed:25266290). Interacts with TGFBRAP1 (By similarity). Component of the putative class C core vacuole/endosome tethering (CORVET) complex; the core of which is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, associated with VPS8 and TGFBRAP1 (PubMed:25266290).|||Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Functions predominantly in APPL1-containing endosomes (By similarity). http://togogenome.org/gene/10090:Sybu ^@ http://purl.uniprot.org/uniprot/Q8BHS8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Golgi apparatus membrane|||Interacts with STX1A and KIF5B.|||Part of a kinesin motor-adapter complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development. http://togogenome.org/gene/10090:Vps13c ^@ http://purl.uniprot.org/uniprot/A1ILG8|||http://purl.uniprot.org/uniprot/Q8BX70 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the VPS13 family.|||Endoplasmic reticulum membrane|||Late endosome membrane|||Lipid droplet|||Lysosome membrane|||Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Necessary for proper mitochondrial function and maintenance of mitochondrial transmembrane potential (By similarity). Involved in the regulation of PINK1/PRKN-mediated mitophagy in response to mitochondrial depolarization (By similarity).|||Mitochondrion outer membrane|||The FFAT motif is required for localization to the endoplasmic reticulum. http://togogenome.org/gene/10090:Tigd4 ^@ http://purl.uniprot.org/uniprot/Q8BUZ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tigger transposable element derived protein family.|||Nucleus http://togogenome.org/gene/10090:Or13e8 ^@ http://purl.uniprot.org/uniprot/Q80ZX9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kng1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J038|||http://purl.uniprot.org/uniprot/D3YTY9|||http://purl.uniprot.org/uniprot/O08677 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bradykinin is inactivated by ACE, which removes the dipeptide Arg-Phe from its C-terminus.|||Bradykinin is released from kininogen by plasma kallikrein.|||Isoform LMW interacts with CRISP3.|||Kininogens are inhibitors of thiol proteases. HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes. LMW-kininogen inhibits the aggregation of thrombocytes. LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting.|||Phosphorylated by FAM20C in the extracellular medium.|||Plasma.|||The active peptide bradykinin is a potent vasodilatator that is released from HMW-kininogen shows a variety of physiological effects: (A) influence in smooth muscle contraction, (B) induction of hypotension, (C) natriuresis and diuresis, (D) decrease in blood glucose level, (E) it is a mediator of inflammation and causes (E1) increase in vascular permeability, (E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action).|||extracellular space http://togogenome.org/gene/10090:Smim33 ^@ http://purl.uniprot.org/uniprot/Q3TS39 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ikzf5 ^@ http://purl.uniprot.org/uniprot/Q8BU00 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Pegasus' was the winged horse in Greek mythology.|||Belongs to the Ikaros C2H2-type zinc-finger protein family.|||C-terminal zinc fingers mediate homodimerization.|||Nucleus|||Self-associates. Interacts with other family members; IKZF1, IKZF2, IKZF3 and IKZF4 (By similarity).|||The N-terminal zinc fingers are involved in sequence-specific DNA binding and heterotypic associations with other family members.|||Transcriptional repressor that binds the core 5'GNNTGTNG-3' DNA consensus sequence (By similarity). Involved in megakaryocyte differentiation (By similarity). http://togogenome.org/gene/10090:Krtap19-5 ^@ http://purl.uniprot.org/uniprot/F8VQ65|||http://purl.uniprot.org/uniprot/O08632 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 19 family.|||Expressed in skin during two hair growth cycles. Expression restricted to the cortical cells of hair follicles, appearing first in the cortical cells processing the flat nuclei located a few cells above the dermal papilla.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Or10d4b ^@ http://purl.uniprot.org/uniprot/Q8VET5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sipa1l3 ^@ http://purl.uniprot.org/uniprot/G3X9J0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Apical cell membrane|||Deficient mice at 4 weeks postnatal age show reduced lens size and microphthalmia (PubMed:26231217).|||Expressed in the developing lens.|||Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). http://togogenome.org/gene/10090:Srgap1 ^@ http://purl.uniprot.org/uniprot/Q91Z69 ^@ Domain|||Function|||Subunit ^@ GTPase-activating protein for RhoA and Cdc42 small GTPases. Together with CDC42 seems to be involved in the pathway mediating the repulsive signaling of Robo and Slit proteins in neuronal migration. SLIT2, probably through interaction with ROBO1, increases the interaction of SRGAP1 with ROBO1 and inactivates CDC42 (By similarity).|||Homodimer (Probable). Forms a heterooligomer with SRGAP2 and SRGAP3 through its F-BAR domain. Interacts with CDC42 and RHOA. Interacts with FASLG (By similarity). Interacts (via SH3 domain) with ROBO1.|||The F-BAR domain mediates oligomerization, binds membranes, and constrains plasma membrane protrusions. http://togogenome.org/gene/10090:Mllt10 ^@ http://purl.uniprot.org/uniprot/O54826 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Probably involved in transcriptional regulation. Binds to cruciform DNA (By similarity). In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (By similarity).|||Self-associates. Interacts with FSTL3; the interaction enhances MLLT10 in vitro transcriptional activity and self-association. Interacts with YEATS4. Interacts with SS18. Interacts with DOT1L (By similarity). Interacts with histone H3; interaction is necessary for MLLT10 binding to nucleosomes; interaction is inhibited by histone H3 'Lys-27' methylations (H3K27me1, H3K27me2 and H3K27me3) amd acetylation; interaction stabilizes association of MLLT10 at chromatin; interaction is essential for histone H3 'Lys-79' dimethylation (H3K79me2) (By similarity). http://togogenome.org/gene/10090:Ly6g5b ^@ http://purl.uniprot.org/uniprot/Q8K1T4 ^@ PTM|||Subcellular Location Annotation|||Subunit ^@ Monomer.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Sult6b2 ^@ http://purl.uniprot.org/uniprot/B7ZWN4 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Pomk ^@ http://purl.uniprot.org/uniprot/Q3TUA9 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Although related to the Ser/Thr protein kinase family, has no protein kinase activity and acts as a mannose kinase instead.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily.|||Endoplasmic reticulum membrane|||Hydrocephaly: mutant mice exhibit dome-shaped heads of varying severity. Surviving mutant mice display numerous behavioral abnormalities: tremors, and inverted screen testing show 5 of 8 falling off, suggesting impaired motor strength. Impaired sensorimotor gating/attention is suggested by decreased prepulse inhibition, and impaired learning/memory is detected with trace aversive conditioning testing. In testing nociception, decreased paw flinching is observed during both formalin phases, suggesting decreased sensitivity to acute and tonic pain. Histologically, the most obvious changes are hydrocephalus in 4 of 5 and cerebellar dysplasia in all 5. Abnormalities in neuronal migration are evident in other parts of the brain; in the cerebral cortex, there is disorganization of cortical neuron layers, and the dentate gyrus of the hippocampus has a scalloped appearance. The cerebellar dysplasia is characterized by multifocal disorganization of cerebellar cortical neurons, with clusters of external granular neurons being scattered on the surface of the cerebellum and multifocally within the molecular layer of the cerebellum. In some regions, there is incomplete separation of cerebellar folia, and Purkinje cell. neurons were occasionally found in the molecular layer.|||Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Only shows kinase activity when the GalNAc-beta-3-GlcNAc-beta-terminus is linked to the 4-position of O-mannose, suggesting that this disaccharide serves as the substrate recognition motif (By similarity). http://togogenome.org/gene/10090:Or6c209 ^@ http://purl.uniprot.org/uniprot/Q8VGI7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Amtn ^@ http://purl.uniprot.org/uniprot/Q9D3J8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amelotin family.|||Expression increases greatly with the transition from secretory to maturation-stage ameloblasts, is maintained during the maturation stage and gradually declines towards the zone of reduced ameloblasts.|||Is a promoter of calcium phosphate mineralization, playing a critical role in the formation of the compact, mineralized, aprismatic enamel surface layer during the maturation stage of amelogenesis.|||O-glycosylated.|||Phosphorylated by FAM20C in vitro.|||Secreted|||Specifically expressed in maturation-stage ameloblasts. http://togogenome.org/gene/10090:Bag5 ^@ http://purl.uniprot.org/uniprot/Q8CI32 ^@ Domain|||Function|||Subunit ^@ Binds to the ATPase domain of HSP/HSP70 chaperones. Binds PRKN (By similarity). Interacts with HSPA8 (PubMed:35044787). Interacts with JPH2 (By similarity).|||Co-chaperone for HSP/HSP70 proteins. It functions as a nucleotide-exchange factor promoting the release of ADP from HSP70, thereby activating HSP70-mediated protein refolding (By similarity). Has an essential role in maintaining proteostasis at junctional membrane complexes (JMC), where it may function as a scaffold between the HSPA8 chaperone and JMC proteins enabling correct, HSPA8-dependent JMC protein folding (PubMed:35044787). Inhibits both auto-ubiquitination of PRKN and ubiquitination of target proteins by PRKN (By similarity).|||The fifth BAG domain is responsible for the interaction with HSP70 nucleotide-binding domain. http://togogenome.org/gene/10090:Nhlh2 ^@ http://purl.uniprot.org/uniprot/Q64221 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Disruption of the hypothalamic-pituitary axis in both genders, but female pubertal development is influenced by the presence or absence of male mice (PubMed:9090387, PubMed:17717072). Altered female sexual behavior and reproductive longevity, with fewer pregnancies over a shorter period, abnormal estrous cycles and reduced ovulation with aging (PubMed:15465527). Reduction in neuroendocrine gonadotropin releasing hormone-1 (GnRH-1) cell number and altered location of these cells, and morphological and functional abnormalities of the adenohypophysis (PubMed:17717072, PubMed:15470499). Ndn expression almost abolished at the level of the optic chiasma in the hypothalamus (PubMed:15470499). Hypothalamic Pcsk1 expression does not respond to signals of energy availability (PubMed:18356286). Progressive adult-onset obesity, preceded by reduced physical activity (PubMed:9090387, PubMed:12419415). Significant reduction in the innervation and vascularization of white adipose tissue and accumulation of preadipocyte/macrophage-like cells, prior to onset of obesity (PubMed:19436734). Defective torpor response and altered serum leptin levels, body temperature and adipose inflammation (PubMed:20808804). Conditional knockout in GnRH neurons but not in pro-opiomelanocortin (POMC) neurons reduces POMC neuron number and increases visceral fat mass (PubMed:23785158). Double knockout of Nhlh1 and Nhlh2 genes causes neonatal lethality, complete absence of GnRH-1 neurons in the posterior parts of the brain at 18.5 days post coitus (dpc) and aberrant morphology of the remaining GnRH-1 neurons in the anterior parts of the brain (PubMed:15470499). Double knockout of Nhlh1 and Nhlh2 genes causes absence of pontine nuclei, which belong to the precerebellar nuclei and are located either side of the midline of the ventral rhombencephalon (PubMed:17573818).|||Expressed in developing neurons (PubMed:1633105). Transiently expressed in the cerebellum during postnatal development, exclusively in the premigratory zone of the external granule layer where postmitotic neurons undergo initial stages of neuronal differentiation (PubMed:9011755). Expression is not detected in mature neurons (PubMed:9011755). Expressed in the anterior lobe of the adult pituitary (PubMed:9090387).|||Expressed in embryos at 10.5-13 days post coitus (dpc), including developing ventral hypothalamus, Rathke's pouch and subventricular layers of the developing diencephalon (PubMed:1633105, PubMed:9090387). Expressed in the vomeronasal organ, olfactory epithelium, and vomeronasal nerve fibers at 14.5 to 16.5 dpc (PubMed:15470499). Expressed in various areas of the developing hypothalamus at 18.5 dpc, including the septal areas, the diagonal band of Broca (DBB), within the organum vasculosum lateralis terminalis (OVLT) region, in the paraventricular nucleus (PVN), in lateral areas of the hypothalamus (LH), in the arcuate nucleus (ARC), and in the dorsomedial hypothalamic nucleus (DMH) (PubMed:15470499). Also expressed in the developing pons from 14.5 dpc onwards, including the pontine and reticulotegmental nuclei (PubMed:17573818).|||Has been reported to be expressed in Rathke's pouch and the developing pituitary gland (PubMed:9090387). However, a later report found no expression in these tissues and speculated that earlier results may represent cross-hybridization with the very similar Nhlh1 gene (PubMed:15470499).|||Homodimer. Interacts and may form heterodimers with STAT3.|||Nucleus|||Transcription factor which binds the E box motif 5'-CA[TC][AG]TG-3' (PubMed:15470499, PubMed:18356286). Involved in regulating energy expenditure, body mass, voluntary physical activity, mating behavior and reproductive longevity, acting through the hypothalamic-pituitary-gonadal axis (PubMed:15470499, PubMed:12419415, PubMed:9090387, PubMed:17717072, PubMed:23785158, PubMed:15465527). Acts as a transcriptional activator of target genes, including Ndn, Pcsk1, Mc4r (PubMed:15470499, PubMed:18356286, PubMed:21664420). Is also a transcriptional activator of KISS1 (By similarity). May act centrally to regulate function of both white and brown adipose tissue (PubMed:20808804, PubMed:19436734). Together with NHLH1, required to maintain migration and survival of cells in the anterior extramural migration stream (aes), which forms the precerebellar nuclei (PubMed:17573818). Also, in concert with Nhlh1, may determine fate of gonadotropin releasing hormone-1 (GnRH-1) neurons (PubMed:15470499). http://togogenome.org/gene/10090:Saa3 ^@ http://purl.uniprot.org/uniprot/P04918 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SAA family.|||Found in various tissues.|||Major acute phase reactant. Apolipoprotein of the HDL complex. In vitro exhibits antimicrobial activity against Escherichia coli, Streptococcus uberis and Pseudomonas aeruginosa (By similarity).|||Secreted|||Upon cytokine stimulation. http://togogenome.org/gene/10090:Ube2g2 ^@ http://purl.uniprot.org/uniprot/P60605|||http://purl.uniprot.org/uniprot/Q3U431 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Involved in endoplasmic reticulum-associated degradation (ERAD). Required for sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation.|||Belongs to the ubiquitin-conjugating enzyme family.|||Endoplasmic reticulum|||Interacts with AUP1 (via C-terminus); the interaction recruits UBE2G2 to lipid droplets. Interacts with ubiquitin ligases AMFR/gp78 and RNF139/TRC8; recruitment to lipid droplets by AUP1 facilitates interaction of UBE2G2 with AMFR and RNF139, leading to sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase and its subsequent proteasomal degradation.|||Lipid droplet http://togogenome.org/gene/10090:Celsr2 ^@ http://purl.uniprot.org/uniprot/Q9R0M0 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Cell membrane|||Expressed in the CNS and in the eye.|||Predominantly expressed in the developing CNS, the emerging dorsal root ganglia and cranial ganglia. In the CNS, expression is uniform along the rostrocaudal axis. During gastrulation, it is expressed within the anterior neural ectoderm. At 10 dpc, expression is strong in the ventricular zones (VZ) in all sectors of the brain, and lower in the marginal zones (MZ). Between 12 and 15 dpc, expression is prominent in the brain. It is strong in VZ, lower in MZ, except in telecephalic MZ where it is predominant. The intensity is higher in all VZ, and lower in differentiating fields than in VZ, except in the cerebral hemispheres, and to a lesser extent in the tectum and cerebellum. A weak expression is also observed in the fetal lungs, kidney and epithelia. In the newborn and postnatal stages, expression remains restricted to the VZ as well as in migrating and postmigratory cells throughout the brain.|||Receptor that may have an important role in cell/cell signaling during nervous system formation.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Dynlt2b ^@ http://purl.uniprot.org/uniprot/Q9CQ66|||http://purl.uniprot.org/uniprot/Q9CQJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system. Required for proper retrograde ciliary transport.|||Belongs to the dynein light chain Tctex-type family.|||Dynein axonemal particle|||Light chain of the cytoplasmic dynein complex 2, a multisubunit complex composed at least of eleven different proteins. The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the dynein-2 complex, but a subset of the light chains are also shared by dynein-1 and dynein-2 complexes. The dimer DYNLT2B-DYNLT1/DYNLT3 interacts with DYNC2I1; this interaction is crucial for retrograde trafficking of ciliary proteins. http://togogenome.org/gene/10090:Drgx ^@ http://purl.uniprot.org/uniprot/Q8BYH0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||Defects in the projection pattern of nociceptive sensory neurons to the dorsal horn of the developing spinal cord leading to reduced sensitivity to painful stimuli. They die within 3 weeks of birth. Mice lacking Drgx exhibit reduced expression of Rgmb in dorsal root ganglion sensory neurons.|||Expressed in the dorsal horn of the spinal cord and dorsal root ganglia. Isoform 1 is higher expressed than isoform 2 both in the dorsal root ganglia and in the spinal cord. Isoform 2 is exclusively localized in neurons primarily involved in the processing of the pain somatosensory modality.|||First detected at 12.5 dpc in newly generated neurons adjacent to the ventricular zone of the dorsal spinal cord. Later expressed in lateral region of the dorsal spinal cord and dorsal root ganglia at 13.5 dpc with increased levels at 15.5 dpc.|||Interacts with RGMB.|||Nucleus|||Transcription factor required for the formation of correct projections from nociceptive sensory neurons to the dorsal horn of the spinal cord and normal perception of pain. http://togogenome.org/gene/10090:Xlr3b ^@ http://purl.uniprot.org/uniprot/Q6P205 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Banf1 ^@ http://purl.uniprot.org/uniprot/O54962 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BAF family.|||Chromosome|||Cytoplasm|||Has a helix-hairpin-helix (HhH) structural motif conserved among proteins that bind non-specifically to DNA.|||Homodimer. Heterodimerizes with BANF2. Interacts with ANKLE2/LEM4, leading to decreased phosphorylation by VRK1 and promoting dephosphorylation by protein phosphatase 2A (PP2A). Binds non-specifically to double-stranded DNA, and is found as a hexamer or dodecamer upon DNA binding. Binds to LEM domain-containing nuclear proteins such as LEMD3/MAN1, TMPO/LAP2 and EMD (emerin). Interacts with ANKLE1 (via LEM domain); the interaction may favor BANF1 dimerization. Interacts with CRX and LMNA (lamin-A). Binds linker histone H1.1 and core histones H3. Interacts with LEMD2 (via LEM domain). Interacts with PARP1; interaction takes place in response to oxidative DNA damage.|||LEM domain proteins bind centrally on the BAF dimer.|||Non-specific DNA-binding protein that plays key roles in mitotic nuclear reassembly, chromatin organization, DNA damage response, gene expression and intrinsic immunity against foreign DNA (By similarity). Contains two non-specific double-stranded DNA (dsDNA)-binding sites which promote DNA cross-bridging (By similarity). Plays a key role in nuclear membrane reformation at the end of mitosis by driving formation of a single nucleus in a spindle-independent manner (By similarity). Transiently cross-bridges anaphase chromosomes via its ability to bridge distant DNA sites, leading to the formation of a dense chromatin network at the chromosome ensemble surface that limits membranes to the surface (By similarity). Also acts as a negative regulator of innate immune activation by restricting CGAS activity toward self-DNA upon acute loss of nuclear membrane integrity (PubMed:32156810). Outcompetes CGAS for DNA-binding, thereby preventing CGAS activation and subsequent damaging autoinflammatory responses (By similarity). Also involved in DNA damage response: interacts with PARP1 in response to oxidative stress, thereby inhibiting the ADP-ribosyltransferase activity of PARP1 (By similarity). Involved in the recognition of exogenous dsDNA in the cytosol: associates with exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown and is required to avoid autophagy (By similarity).|||Nucleus|||Nucleus envelope|||Ser-4 is the major site of phosphorylation as compared to Thr-2 and Thr-3. Phosphorylation on Thr-2; Thr-3 and Ser-4 disrupts its ability to bind DNA and reduces its ability to bind LEM domain-containing proteins. Non phosphorylated BAF seems to enhance binding between EMD and LMNA. Dephosphorylated by protein phosphatase 2A (PP2A) following interaction with ANKLE2/LEM4 during mitotic exit, leading to mitotic nuclear envelope reassembly. http://togogenome.org/gene/10090:Ubr5 ^@ http://purl.uniprot.org/uniprot/Q80TP3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ A cysteine residue is required for ubiquitin-thioester formation.|||Binds TOPBP1. Associates with CDK9 and TFIIS/TCEA1 and forms a transcription regulatory complex made of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription by recruiting their promoters. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Interacts directly with DYRK2. Interacts with PIH1D1.|||E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (By similarity). Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Plays an essential role in extraembryonic development. Regulates DNA topoisomerase II binding protein (TopBP1) for the DNA damage response.|||Nucleus http://togogenome.org/gene/10090:Nfam1 ^@ http://purl.uniprot.org/uniprot/Q8R4V1 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Highest expression in pro-B-cells decreases with B-cell differentiation.|||Highly expressed in the spleen, expressed by both B- and CD4+ and CD8+ T-cells, as well as non-T- and non-B-cells, including macrophages and neutrophils. Expressed at low levels, if any, in non-immune tissue.|||May function in immune system as a receptor which activates via the calcineurin/NFAT-signaling pathway the downstream cytokine gene promoters. Activates the transcription of IL-13 and TNF-alpha promoters (By similarity). May be involved in the regulation of B-cell, but not T-cell, development.|||N-glycosylated.|||No direct interaction with the B-cell antigen receptor (BCR). Interacts with SYK; probably involved in BCR signaling. Interacts with ZAP70.|||The ITAM domain displays no close similarity to any existing ITAMs, except for four conserved positions. The phosphorylated ITAM domain binds ZAP70 and SYK. http://togogenome.org/gene/10090:Actrt2 ^@ http://purl.uniprot.org/uniprot/Q9D9L5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the actin family.|||cytoskeleton http://togogenome.org/gene/10090:Ung ^@ http://purl.uniprot.org/uniprot/P97931|||http://purl.uniprot.org/uniprot/Q791V7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the uracil-DNA glycosylase (UDG) superfamily. UNG family.|||Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.|||Isoform 1 is processed by cleavage of a transit peptide.|||Mitochondrion|||Monomer. Interacts with FAM72A.|||Nucleus http://togogenome.org/gene/10090:Dnajb1 ^@ http://purl.uniprot.org/uniprot/Q9QYJ3 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By heat shock.|||Cytoplasm|||Interacts with DNAJC3. Interacts with HSF1 (via transactivation domain); this interaction results in the inhibition of heat shock- and HSF1-induced transcriptional activity during the attenuation and recovery phase period of the heat shock response.|||Interacts with HSP70 and can stimulate its ATPase activity. Stimulates the association between HSC70 and HIP. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Dctn6 ^@ http://purl.uniprot.org/uniprot/D3Z4E5|||http://purl.uniprot.org/uniprot/D3Z6H3|||http://purl.uniprot.org/uniprot/Q9WUB4 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynactin subunits 5/6 family. Dynactin subunit 6 subfamily.|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.|||Phosphorylation at Thr-186 by CDK1 during mitotic prometaphase creates a binding site for PLK1 that facilitates its recruitment to kinetochores.|||Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. Within the complex DCTN6 forms a heterodimer with DCTN5 (By similarity). The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with PLK1 (By similarity).|||Up-regulated in Ant1-deficient mice.|||cytoskeleton|||kinetochore http://togogenome.org/gene/10090:Gbx1 ^@ http://purl.uniprot.org/uniprot/P82976 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed first during gastrulation and later in a dynamic pattern in the central nervous system.|||Expressed in CNS including rhombomeres 3 and 5, optic vesicles, and the medial ganglionic eminence.|||Nucleus http://togogenome.org/gene/10090:Klhl13 ^@ http://purl.uniprot.org/uniprot/Q80TF4 ^@ Function|||Subunit ^@ Component of the BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL9, KLHL13 and RBX1. Interacts with AURKB (By similarity).|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis (By similarity). http://togogenome.org/gene/10090:Atg4c ^@ http://purl.uniprot.org/uniprot/Q3UYA5|||http://purl.uniprot.org/uniprot/Q811C2 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C54 family.|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine (By similarity). Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy (By similarity). In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy. Compared to ATG4B, the major protein for proteolytic activation of ATG8 proteins, shows weaker ability to cleave the C-terminal amino acid of ATG8 proteins, while it displays stronger delipidation activity. In contrast to other members of the family, weakly or not involved in phagophore growth during mitophagy (By similarity).|||Cytoplasm|||Inhibited by N-ethylmaleimide.|||Was reported that this protein is required for a proper autophagic response under stressful conditions such as prolonged starvation, based on experiments conducted on cells or mice claimed to have null alleles (PubMed:17442669). However, this paper has been retracted because of aberrations in the relevant figure (PubMed:30808006). Nevertheless, a separate experiment in the same paper suggests that the alleles are null and so the inferred function may be true. http://togogenome.org/gene/10090:Kif3c ^@ http://purl.uniprot.org/uniprot/O35066|||http://purl.uniprot.org/uniprot/Q571A6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin II subfamily.|||Heterodimer of KIF3A and KIF3C.|||Microtubule-based anterograde translocator for membranous organelles.|||cytoskeleton http://togogenome.org/gene/10090:Aar2 ^@ http://purl.uniprot.org/uniprot/Q8C161|||http://purl.uniprot.org/uniprot/Q9D2V5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the AAR2 family.|||Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.|||Interacts with PRPF8 (via RNase H homology domain) (By similarity). Component of a U5 snRNP complex that contains PRPF8 (By similarity). http://togogenome.org/gene/10090:Tm4sf20 ^@ http://purl.uniprot.org/uniprot/Q9CQY8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the L6 tetraspanin family.|||Cleaved by signal peptidase at Ser-14 but the peptide does not act as a signal peptide. Cleavage is inhibited by ceramide which inverts the orientation of TM4SF20 in membranes exposing the N-terminus to the cytosol and not to the endoplasmic reticulum lumen.|||Endoplasmic reticulum membrane|||Glycosylated at Asn-132, Asn-148 and Asn-163 in presence of ceramide which inverts the orientation of TM4SF20 in membranes exposing these residues to the endoplasmic reticulum lumen.|||Membrane|||Polytopic transmembrane protein. Inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis. In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1. Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein.|||The first transmembrane helix plays a critical role for the insertion orientation in the endoplasmic reticulum membrane. http://togogenome.org/gene/10090:Psmd13 ^@ http://purl.uniprot.org/uniprot/B2RT97|||http://purl.uniprot.org/uniprot/Q9WVJ2 ^@ Function|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the proteasome subunit S11 family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD13, a base containing 6 ATPases and few additional components.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.|||Intron retention. http://togogenome.org/gene/10090:Txndc15 ^@ http://purl.uniprot.org/uniprot/Q6P6J9 ^@ Function|||Subcellular Location Annotation ^@ Acts as a positive regulator of ciliary hedgehog signaling (PubMed:29459677). Required for cilia biogenesis (PubMed:29459677).|||cilium membrane http://togogenome.org/gene/10090:Defa31 ^@ http://purl.uniprot.org/uniprot/Q5G866 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Pals1 ^@ http://purl.uniprot.org/uniprot/B2RRY4|||http://purl.uniprot.org/uniprot/Q9JLB2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the MAGUK family.|||Cell membrane|||Conditional knockout in the retina results in mice which are viable, fertile, and morphologically normal apart from microphthalmia with severe defects in visual response (PubMed:22398208). From 13.5 days post-conception (dpc) retinas show variable morphology, including retinal folding, variable thickness and disorganization (PubMed:22398208). Postnatally the retinal lamina is thinner, and disorganized, with a shortening or absence of the inner and outer segments of photoreceptor cells (PubMed:22398208). By postnatal day 60 retinas are completely or partially devoid of the outer nuclear layers and photoreceptor layer, and feature a reduced number of photoreceptor cells, disrupted cell polarity and impaired distribution of retinal neurons (PubMed:22398208). Retinal distribution of Par3 and the Crb polarity complex proteins Crbs and Patj is disrupted (PubMed:22398208). Mature mice show aberrant proliferation and apoptosis of retinal epithelia with significantly reduced or undetectable a- and b-waves in electroretinogram-measured dark-adapted response (PubMed:22398208). Conditional knockout in cerebellum proliferating progenitors at 13.5 dpc results in mislocalization of apical polarity complex proteins such as Crb proteins, Pard3, and Prkci at 15.5 dpc (PubMed:26657772). Following cerebellum conditional knockout there is an increase in migration and premature differentiation of Pax2-positive ventricular zone cells at 17.5 dpc, resulting in a reduced number of glial cell progenitors (PubMed:26657772). Conditional knockout in cerebellum results in stunted cerebellum growth and indistinct vermis foliation at birth, there is also an evident reduction of Bergmann glia, oligodendrocyte, astrocyte and GABAergic interneuron progenitors (PubMed:26657772). Conditional knockout in cerebellum shows compromised Purkinje cell migration and formation failure of Purkinje cell plate to contain both Bergmann glia and Purkinje cells, possibly as a result of abnormal Reln-Dab1 signaling at P6 (PubMed:26657772). Conditional knockout in cerebellum results in poorly layered, smaller lobes, severe defects in fissure formation and a reduced number of cerebellar granule neurons and GABAergic interneurons from P8 to P21 (PubMed:26657772). Conditional knockout in the cortex results in mice surviving to adulthood, with lower body weight but exhibit irregular movements with disrupted stride and gait, reduced exploratory initiative, reduced locomotor behavior and swim in circles (PubMed:20399730). Reduced cortical size and disrupted morphology at 12 and 14 dpc resulting in the absence of the cortex postnatally lacking virtually all cortical neurons, additionally extreme thinning of the lateral cortex is observed (PubMed:20399730). Reduced proliferation of cortical progenitor cells and increased cell death of postmitotic neurons in the developing medial cortex and ventral zone from 10.5 dpc, additionally mislocalization and reduced abundance of Crb2 and Prkci is evident (PubMed:20399730). RNAi-mediated knockdown in the sciatic nerve results in mislocalization of Exoc4/Sec8 and Stx4 in Schwann cells and thinning and shortening of Schwann cells as a result of a reduction in the myelinated fiber diameter caused by fewer myelin turns (PubMed:20237282). Conditional knockout of both Mpp3 and Pals1 in the retina results in an increase in retinal degeneration that becomes evident at one month of age (PubMed:23893895).|||Endomembrane system|||Expressed in the developing sciatic nerve, with increasing expression from newborn to postnatal day 20, and decreasing expression at postnatal day 60 (P60) (at protein level) (PubMed:20237282). Expressed in the developing neural tube, optic vesicle, branchial arches and kidney at 10.5 dpc (PubMed:17920587). Expressed in the ventricular layers of the developing neural tube along the entire cranial-caudal length, including the anterior forebrain and the posterior spinal cord at 11.5 dpc (PubMed:17920587). Highly expressed in cortical progenitor cells at 12 dpc, expression decreases during neurogenesis but weak expression is still present at birth (PubMed:20399730). Expressed in the developing brain at 15.5 dpc in the upper rhombic lip, ventricular zone, and external granule layer (EGL) (at protein level) (PubMed:26657772). At birth expressed in the ventricular apical lining cells, proliferating external granule layer and Purkinje cell layer (PCL), with expression remaining abundant in the EGL and weakly evident in the PCL at P6 (at protein level) (PubMed:26657772). Expressed at P8 in the EGL, cerebellar granule neuron precursors, Bergmann glia, Pcna-positive progenitor cells in the white matter, and weakly in Pax6-positive postmitotic granule neurons (at protein level) (PubMed:26657772). Expressed weakly throughout the retina between 12.5 dpc and 14.5 dpc, becoming enriched in progenitors at the outer neuroblastic layer at 14.5 dpc (PubMed:22398208). Expressed in the retinal layer of the optic vesicle, and weakly expressed in the retinal pigment epithelium at 12.5 dpc (PubMed:17920587). Localized to the apical edge of the retina between 12.5 and 16.5 dpc (PubMed:22398208). Expressed in the internal endodermal layer and in the developing saccules of the lung at 11.5 dpc (PubMed:17920587). Expressed at the outer limiting membrane of the retina at 18.5 dpc and 3 months of age (PubMed:23001562).|||Expressed in the retinal pigment epithelium (at protein level) (PubMed:15558731, PubMed:22398208, PubMed:23893895, PubMed:26404741). Expressed in the vascular plexus of the retina (at protein level) (PubMed:27466317). In the brain, expressed in the dentate gyrus of hippocampus, striatum and cerebellum (at protein level) (PubMed:15234345, PubMed:26404741). Expressed in the sciatic nerve (at protein level) (PubMed:20237282). Expressed in the kidney nephron (at protein level) (PubMed:10753959, PubMed:15558731). Expressed in the lung, and heart (PubMed:10753959, PubMed:15558731). Expressed in placenta, brain, skeletal muscles, pancreas and liver (PubMed:10753959).|||Golgi apparatus|||Heterodimer with MPP1 (By similarity). Forms a heterotrimeric complex composed of PALS1, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (By similarity). Component of a complex composed of PALS1, CRB1 and MPP4 (By similarity). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3 (By similarity). Component of a complex composed of PALS1, CRB1 and EPB41L5 (By similarity). Within the complex, interacts (via HOOK domain) with EPB41L5 (via FERM domain), and interacts with CRB1 (via intracellular domain) (By similarity). Component of a complex composed of PALS1, MPP3 and CRB1; PALS1 acts as a bridging protein between MPP3 (via guanylate kinase-like domain) and CRB1 (PubMed:16519681). Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via PDZ domain) with PATJ (via N-terminus) (PubMed:11927608, PubMed:12527193, PubMed:20399730). Interacts with EZR (PubMed:15677456). Interacts (via PDZ domain) with CRB1 (via C-terminal ERLI motif) (By similarity). While the PDZ domain is sufficient for interaction with CRB1, the adjacent SH3 and guanylate kinase-like domains are likely to contribute to a high affinity interaction (By similarity). Interacts with WWTR1/TAZ (via WW domain) (PubMed:21145499). Interacts with MPP7 (By similarity). Interacts (via PDZ domain) with CRB3 (via C-terminus) (PubMed:12527193). Interacts with LIN7C (PubMed:10753959). Interacts with MPDZ (PubMed:15316081). Interacts with PARD6B (PubMed:12545177, PubMed:15140881). Interacts with SC6A1 (PubMed:15234345). Interacts with CDH5; the interaction promotes PALS1 localization to cell junctions and is required for CDH5-mediated vascular lumen formation and endothelial cell (PubMed:27466317). Interacts with NPHP1 (via coiled coil and SH3 domains) (By similarity). Interacts with NPHP4 (By similarity). Interacts with CRB2 (PubMed:20399730).|||Perikaryon|||Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (By similarity). Also involved in adherens junction biogenesis by ensuring correct localization of the exocyst complex protein EXOC4/SEC8 which allows trafficking of adherens junction structural component CDH1 to the cell surface (PubMed:17182851, PubMed:20237282). Plays a role through its interaction with CDH5 in vascular lumen formation and endothelial membrane polarity (By similarity). Required during embryonic and postnatal retinal development (PubMed:22398208). Required for the maintenance of cerebellar progenitor cells in an undifferentiated proliferative state, preventing premature differentiation, and is required for cerebellar histogenesis, fissure formation, cerebellar layer organization and cortical development (PubMed:20399730, PubMed:26404741). Plays a role in neuronal progenitor cell survival, potentially via promotion of mTOR signaling (PubMed:20399730). Plays a role in the radial and longitudinal extension of the myelin sheath in Schwann cells (PubMed:20237282). May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter (PubMed:15234345). May play a role in the T-cell receptor-mediated activation of NF-kappa-B (By similarity). Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (PubMed:15677456). Required for the normal polarized localization of the vesicular marker STX4 (PubMed:20237282). Required for the correct trafficking of the myelin proteins PMP22 and MAG (By similarity). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (PubMed:21145499).|||The L27 domain 1 functions in targeting to the tight junctions by binding to and stabilizing PATJ.|||The PDZ domain binds to the C-terminus of SC6A1.|||adherens junction|||axon|||tight junction http://togogenome.org/gene/10090:Rnf112 ^@ http://purl.uniprot.org/uniprot/Q96DY5 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Cytoplasm|||E3 ubiquitin-protein ligase that plays an important role in neuronal differentiation, including neurogenesis and gliogenesis, during brain development. During embryonic development initiates neuronal differentiation by inducing cell cycle arrest at the G0/G1 phase through up-regulation of cell-cycle regulatory proteins (PubMed:21566658, PubMed:28684796). Plays a role not only in the fetal period during the development of the nervous system, but also in the adult brain, where it is involved in the maintenance of neural functions and protection of the nervous tissue cells from oxidative stress-induced damage (PubMed:27918959, PubMed:26792191, PubMed:26951452). Exhibits GTPase and E3 ubiquitin-protein ligase activities. Regulates dendritic spine density and synaptic neurotransmission; its ability to hydrolyze GTP is involved in the maintenance of dendritic spine density (PubMed:26212327).|||Embryos exhibit blood vascular defects and die in utero. The survivors manifest growth retardation as indicated by smaller size and a reduced weight, and display impairment of brain functions including motor balance, and spatial learning and memory (PubMed:26951452). Mice exhibit a reduction in the size of brains, reduced dendritic spine density, impaired synaptic transmission and reduced levels of antioxidant enzymes in the hippocampus (PubMed:26792191, PubMed:26212327). Knockdown of RNF112 diminishes neuronal differentiation, glial differentiation and dendritic arborization in primary cerebellar granule cells (PubMed:28684796, PubMed:21566658).|||Endosome|||Expressed in most of the brain areas, including cortex, striatum, hippocampus, thalamus, and cerebellum (at protein level). Expressed in lateral amygdaloid nucleus, and ventromedial hypothalamus. Also expressed strongly in the marginal zone of brain vesicles, optic stalk, and cartilage primordium.|||Membrane|||Nucleus|||Perikaryon|||Postsynaptic density|||Self-associates (PubMed:26212327). Interacts with SP1 in an oxidative stress-regulated manner (PubMed:27918959). Interacts with SIGMAR1 in an oxidative stress-regulated manner (PubMed:26792191). Interacts with ZBTB16 (via C2H2-type zinc finger domains 1 and 2) (PubMed:24359566).|||Up-regulated by traumatic brain injury and hydrogen peroxide (at protein level).|||neuron projection|||nuclear body|||nucleoplasm|||synaptic vesicle http://togogenome.org/gene/10090:Sh2b1 ^@ http://purl.uniprot.org/uniprot/Q91ZM2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity (By similarity). Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis, according the order: isoform 3 > isoform 4 > isoform 1 > isoform 2.|||Belongs to the SH2B adapter family.|||Cytoplasm|||Membrane|||Nucleus|||Phosphorylated on tyrosine residues in response to IGF-I and PDGF stimulation.|||Self-associates. Homopentamer (By similarity). Forms a heteromultimeric complex with SH2B2 (By similarity). Interacts with SH2B2. Isoform 1 interacts via its SH2 domain with JAK2. Isoform 2 interacts via its SH2 domain and its N-terminus with JAK2; the SH2 domain is required for the major interaction with JAK2 phosphorylated on tyrosine residues; the N-terminus provides a low-affinity binding to JAK2 independent of JAK2 phosphorylation. Isoform 3 interacts via its SH2 domain with JAK2. Isoform 1 interacts via its SH2 domain with INSR; the interaction requires receptor activation. Isoform 3 interacts via its SH2 domain with INSR; the interaction requires receptor activation and requires INSR phosphorylation at 'Tyr-1175'. Isoform 1 interacts with IGF1R; the interaction requires receptor activation. Isoform 2 interacts via its SH2 domain with FGFR3; the interaction requires FGFR3 'Tyr-719' and 'Tyr-755'. Isoform 2 interacts with RET; the interaction requires RET kinase activity and RET 'Tyr-982'. Isoform 2 interacts with RAC1. Isoform 2 interacts with PDGFRA and/or PDGFRB; the interaction requires receptor activation. Interacts with ISR1 and ISR2. Isoform 3 is probably part of a complex consisting of INSR, ISR1 and SH2B1. Probably part of a ternary complex consisting of SH2B1, JAK2 and ISR1 or ISR2. May interact with FCER1G (By similarity). Interacts (via SH2 domain) with NTRK1 (phosphorylated) (By similarity).|||Widely expressed with highest levels in liver, brain and heart. Isoform 3 is widely expressed. http://togogenome.org/gene/10090:Bcat2 ^@ http://purl.uniprot.org/uniprot/O35855|||http://purl.uniprot.org/uniprot/O88374|||http://purl.uniprot.org/uniprot/Q3ULU3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine (By similarity). May also function as a transporter of branched chain alpha-keto acids (By similarity).|||Homodimer.|||Mitochondrion http://togogenome.org/gene/10090:Pmepa1 ^@ http://purl.uniprot.org/uniprot/A2APF4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PMEPA1 family.|||Early endosome membrane|||Endosome membrane|||Membrane http://togogenome.org/gene/10090:Or8b4 ^@ http://purl.uniprot.org/uniprot/Q9EQA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Shank1 ^@ http://purl.uniprot.org/uniprot/D3YZU1|||http://purl.uniprot.org/uniprot/D3YZU4|||http://purl.uniprot.org/uniprot/D3YZU5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SHANK family.|||Cytoplasm|||In brain, highly expressed in cortex, hippocampus and cerebellum.|||May homomultimerize via its SAM domain. Interacts with the C-terminus of SSTR2 via the PDZ domain. Interacts with SHARPIN, SPTAN1, HOMER1 and DLGAP1/GKAP. Part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts with BAIAP2. Interacts with IGSF9 (By similarity). Interacts with HOMER1 and HOMER3 (By similarity).|||Postsynaptic density|||Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction. Overexpression promotes maturation of dendritic spines and the enlargement of spine heads via its ability to recruit Homer to postsynaptic sites, and enhances presynaptic function (By similarity).|||Synapse http://togogenome.org/gene/10090:Or5i1 ^@ http://purl.uniprot.org/uniprot/G3X9L8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyb5a ^@ http://purl.uniprot.org/uniprot/G5E850|||http://purl.uniprot.org/uniprot/P56395|||http://purl.uniprot.org/uniprot/Q544Z9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome b5 family.|||Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases. It is also involved in several steps of the sterol biosynthesis pathway, particularly in the C-5 double bond introduction during the C-5 desaturation.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Slc4a2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J101|||http://purl.uniprot.org/uniprot/A0A0R4J1K4|||http://purl.uniprot.org/uniprot/A0A0R4J1K9|||http://purl.uniprot.org/uniprot/P13808|||http://purl.uniprot.org/uniprot/Q3UKP0|||http://purl.uniprot.org/uniprot/Q7TPS4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Expressed at slightly higher levels in lung and stomach than in other tissues.|||Expressed in the choroid plexus epithelium (at protein level) (PubMed:2371270). Expressed in the parotid gland and sublingual salivary gland acinar cells (at protein level) (PubMed:12958022).|||Inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and acetazolamide (PubMed:2371270, PubMed:12958022). Muscarinic receptor stimulation enhances activity through a Ca(2+)-dependent mechanism (PubMed:12958022).|||Male mice are infertile and the size and weight of the testis is reduced by 40-60%. Spermiogenesis is interrupted after stage VII, with only a few late spermatids and a complete absence of spermatozoa in the seminiferous tubules. The number of apoptotic bodies is increased in the seminiferous tubules and in the epididymis, which also shows squamous metaplasia of the epididymal epithelium (PubMed:14673081). CD8(+) T-cells exhibit increased intracellular pH and enhanced cell proliferation and activation after CD3 stimulation (PubMed:24515893). Mice display osteopetrosis with osteoclasts showing abnormal differentiation and increased apoptosis (PubMed:18971331). Conditional knockout in osteoclasts (OCs) result in dysfunctional OCs which exhibit altered intracellular pH and actin cytoskeletal dynamics and an impaired bone resorption capacity owing to a dysregulation of calpain-dependent podosomal disassembly (PubMed:23341620).|||Membrane|||Plays a critical role in male fertility and spermiogenesis.|||Predominantly expressed in stomach although they are also detected at lower levels in other tissues (PubMed:11006093). Expressed in the testis (PubMed:14673081).|||Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:2371270, PubMed:12958022, PubMed:18971331, PubMed:23341620, PubMed:24515893). Plays an important role in osteoclast differentiation and function (PubMed:18971331, PubMed:23341620). Regulates bone resorption and calpain-dependent actin cytoskeleton organization in osteoclasts via anion exchange-dependent control of pH (PubMed:23341620). Essential for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation, modulating CD8(+) T-cell responses (PubMed:24515893).|||Stomach-specific.|||Up-regulated during osteoclast differentiation.|||Widely expressed at similar levels in all tissues examined (PubMed:11006093). Expressed in the testis (PubMed:14673081). http://togogenome.org/gene/10090:Tfb1m ^@ http://purl.uniprot.org/uniprot/Q8JZM0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family. KsgA subfamily.|||Interacts with mitochondrial RNA polymerase POLRMT. Interacts with TFAM (By similarity).|||Mitochondrion|||S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity (By similarity).|||Ubiquitously expressed. http://togogenome.org/gene/10090:Pcdha6 ^@ http://purl.uniprot.org/uniprot/Q91Y14 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Psmg3 ^@ http://purl.uniprot.org/uniprot/Q9CZH3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PSMG3 family.|||Chaperone protein which promotes assembly of the 20S proteasome. May cooperate with PSMG1-PSMG2 heterodimers to orchestrate the correct assembly of proteasomes.|||Homodimer. Interacts directly with alpha and beta subunits of the 20S proteasome but dissociates before the formation of half-proteasomes, probably upon recruitment of POMP (By similarity). Interacts with PSMG4. http://togogenome.org/gene/10090:Upk3b ^@ http://purl.uniprot.org/uniprot/Q80YF6 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the uroplakin-3 family.|||Cell membrane|||Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells. It also contributes to the formation of urothelial glycocalyx which may play an important role in preventing bacterial adherence (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Expression is urothelium-specific.|||Heterodimer with uroplakin-1B (UPK1B). http://togogenome.org/gene/10090:Fstl5 ^@ http://purl.uniprot.org/uniprot/Q8BFR2 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Lyrm1 ^@ http://purl.uniprot.org/uniprot/Q9CQB7 ^@ Function|||Similarity ^@ Belongs to the complex I LYR family.|||May promote cell proliferation and inhibition of apoptosis of preadipocytes. http://togogenome.org/gene/10090:Nr2f6 ^@ http://purl.uniprot.org/uniprot/P43136 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1. Interacts with THRB (By similarity).|||Initially expressed at 8.5 dpc in the developing rhombencephalon. At 11.5 dpc expression in the CNS rapidly decreases and in newborn and adult expression is not detectable in the brain with the exceptions of Purkinje neurons and the choroid plexi.|||Nucleus|||Reduction of neurons in the locus coerulus of the developing cortex. Defects in circadian behavior. Hyperreactive lymphocytes, late-onset immunopathology and hypersusceptibility to Th17-dependent experimental autoimmune encephalomyelitis.|||Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4(+) T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). http://togogenome.org/gene/10090:Ercc8 ^@ http://purl.uniprot.org/uniprot/Q8CFD5 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Ercc8 deficient mice develop normally, but show a loss of retinal photoreceptors after 4 months of age, and enhanced UV-sensitivity.|||Nucleus|||Nucleus matrix|||Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Interacts with ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II TFIIH. Interacts with DDB1.|||Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair (By similarity). The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair (By similarity). It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes (By similarity). Plays a role in DNA single-strand and double-strand breaks (DSSBs) repair; involved in repair of DSSBs by non-homologous end joining (NHEJ) (By similarity). http://togogenome.org/gene/10090:Ecm2 ^@ http://purl.uniprot.org/uniprot/Q5FW85 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 16.5 dpc, present in periosteum of ribs. At P0, present in tendons connecting the scapula and humerus to muscles (at protein level).|||Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.|||Interacts with numerous extracellular matrix proteins (PubMed:18757743). Interacts with isoform 1 of MSL1 (PubMed:17335777). Interacts with isoform 3 of RASSF1 (PubMed:17335777).|||Promotes matrix assembly and cell adhesiveness.|||extracellular matrix http://togogenome.org/gene/10090:Or8u10 ^@ http://purl.uniprot.org/uniprot/Q7TR84 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ostm1 ^@ http://purl.uniprot.org/uniprot/Q8BGT0 ^@ Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OSTM1 family.|||Chloride channel 7 are heteromers of alpha (CLCN7) and beta (OSTM1) subunits.|||Defects in Ostm1 are the cause of the spontaneous gray-lethal (gl) mutant, which is responsible for a coat color defect and for the development of the most severe autosomal recessive form of osteopetrosis. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood.|||Expressed primarily in osteoclasts and melanocytes as well as brain, kidney and spleen. Found at lower levels in the thymus, testis, heart and liver.|||Expression was detected in fetal liver neuronal and bone tissues (12.5 dpc and 15.5 dpc). High expression was detected in thymus and gut at 18.5 dpc and continued postnatally. Expression in bone (mandible and vertebrae) and brain tissues (cerebellum, hippocampus and cortex) remained high after birth. In addition high expression was detected in kidney, spleen and skin at P5 and P10.|||Highly N-glycosylated.|||Lysosome membrane|||Required for osteoclast and melanocyte maturation and function.|||Undergoes proteolytic cleavage in the luminal domain, the cleaved fragments might be linked by disulfide bonds with the remnant of the protein. http://togogenome.org/gene/10090:Loxhd1 ^@ http://purl.uniprot.org/uniprot/C8YR32 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the inner ear, specifically in hair cells. Higher expression is detected in the cochlea.|||Required for normal function of hair cells in the inner ear.|||stereocilium http://togogenome.org/gene/10090:Lacc1 ^@ http://purl.uniprot.org/uniprot/Q8BZT9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.|||Cytoplasm|||Endoplasmic reticulum|||Interacts with FASN. Interacts with SDHA. Interacts with ATF6, EIF2AK3 and ERN1.|||No visible phenotype in normal conditions (PubMed:30510070). Mice show increased inflammatory response in mouse models of arthritis and inflammation (PubMed:30510070).|||Nucleus|||Peroxisome|||Phosphorylated on tyrosine residues.|||Predominantly expressed in myeloid cells (PubMed:30510070). Highly expressed in primary macrophages and dendritic cells sorted from the peritoneum or spleen, respectively (at protein level) (PubMed:30510070).|||Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine, guanosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine, guanine and hypoxanthine (By similarity). Also catalyzes the phosphorolysis of S-methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate (By similarity). Also has adenosine deaminase activity (By similarity). Acts as a regulator of innate immunity in macrophages by modulating the purine nucleotide metabolism, thereby regulating the metabolic function and bioenergetic state of macrophages (PubMed:27478939, PubMed:31978345). Enables a purine nucleotide cycle between adenosine and inosine monophosphate and adenylosuccinate that prevents cytoplasmic acidification and balances the cytoplasmic-mitochondrial redox interface (PubMed:31978345). The purine nucleotide cycle consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity (PubMed:31978345). Participates in pattern recognition receptor-induced cytokines in macrophages: associates with the NOD2-signaling complex and promotes optimal NOD2-induced signaling, cytokine secretion and bacterial clearance (By similarity). Localizes to the endoplasmic reticulum upon PRR stimulation of macrophages and associates with endoplasmic reticulum-stress sensors, promoting the endoplasmic reticulum unfolded protein response (UPR) (By similarity). Does not show laccase activity (By similarity). http://togogenome.org/gene/10090:Or8k27 ^@ http://purl.uniprot.org/uniprot/Q7TR70 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r7 ^@ http://purl.uniprot.org/uniprot/E9Q8T0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam170a ^@ http://purl.uniprot.org/uniprot/Q66LM6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a nuclear transcription factor that positively regulates the expression of heat shock genes. Binds to heat shock promoter elements (HSE).|||Belongs to the FAM170 family.|||Nucleus|||Testis-specific.|||The N-terminus is necessary for nuclear localization. The C-terminus is necessary for transcriptional activity (By similarity). http://togogenome.org/gene/10090:Zkscan1 ^@ http://purl.uniprot.org/uniprot/Q8BGS3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Dcxr ^@ http://purl.uniprot.org/uniprot/Q91X52 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the NADPH-dependent reduction of several pentoses, tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose. Participates in the uronate cycle of glucose metabolism. May play a role in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thereby preventing osmolytic stress from occurring in the renal tubules.|||Highly expressed in kidney, liver and epididymis. Expressed at intermediate level in lung. Weakly or not expressed in brain, heart, spleen and testis.|||Homotetramer.|||Membrane http://togogenome.org/gene/10090:Sprr2a1 ^@ http://purl.uniprot.org/uniprot/Q4KL71|||http://purl.uniprot.org/uniprot/Q9CQK8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cornifin (SPRR) family.|||By type-2 cytokines IL4 and IL13 in response to helminth infection.|||Forms five pairs of intrachain disulfide bonds.|||Gut bactericidal protein that selectively kills Gram-positive bacteria by binding to negatively charged lipids on bacterial membranes, leading to bacterial membrane permeabilization and disruption (PubMed:34735226). Specifically binds lipids bearing negatively charged headgroups, such as phosphatidic acid, phosphatidylserine (PS), cardiolipin (CL), and phosphatidylinositol phosphates, but not to zwitterionic or neutral lipids (By similarity). Induced by type-2 cytokines in response to helminth infection and is required to protect against helminth-induced bacterial invasion of intestinal tissue (PubMed:34735226). May also be involved in the development of the cornified envelope of squamous epithelia; however, additional evidences are required to confirm this result in vivo (By similarity).|||Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an expansion of Gram-positive bacteria in the small intestinal lumen and mucus layer (PubMed:34735226). Mice were born in normal Mendelian ratios, are healthy and show normal intestinal morphology with no signs of inflammation in normal conditions (PubMed:34735226). They however show an increased abundance of Gram-positive bacteria in the small intestinal lumen, with a marked increase in the relative abundance of Lactobacillus, Turicibacter, and C.Arthromitus (PubMed:34735226). At the same time, a reduction in the abundance of Bacteroidetes, a class of Gram-negative bacteria is observed (PubMed:34735226). Mice are more susceptible to L. monocytogenes infection (PubMed:34735226).|||Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an expansion of Gram-positive bacteria in the small intestinal lumen and mucus layer (PubMed:34735226). Mice were born in normal Mendelian ratios, are healthy and show normal intestinal morphology with no signs of inflammation in normal conditions (PubMed:34735226). They however show an increased abundance of Gram-positive bacteria in the small intestinal lumen, with a marked increase in the relative abundance of Lactobacillus, Turicibacter, and C.arthromitus (PubMed:34735226). At the same time, a reduction in the abundance of Bacteroidetes, a class of Gram-negative bacteria is observed (PubMed:34735226). Mice are more susceptible to L. monocytogenes infection (PubMed:34735226).|||Secreted|||extracellular space|||secretory vesicle http://togogenome.org/gene/10090:Cyp2j13 ^@ http://purl.uniprot.org/uniprot/B1AWM4|||http://purl.uniprot.org/uniprot/B1AWM5|||http://purl.uniprot.org/uniprot/Q3UNV4 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Tm7sf2 ^@ http://purl.uniprot.org/uniprot/Q71KT5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ERG4/ERG24 family.|||Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis.|||Endoplasmic reticulum membrane|||Mice develop normally, appear healthy and are fertile.|||Microsome membrane|||Strongly expressed in liver, weaker in ovary, testis, kidney and brain. http://togogenome.org/gene/10090:Pln ^@ http://purl.uniprot.org/uniprot/P61014 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholamban family.|||Endoplasmic reticulum membrane|||Expressed in testis (at protein level).|||Homopentamer (PubMed:26644582). Interacts with HAX1. Interact with ATP2A2; the inhibition decreases ATP2A2 Ca(2+) affinity. Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2. Interacts with S100A1 in a Ca(2+)-dependent manner.|||In elongated spermatids, proteolytically cleaved by SPPL2C which modulates intracellular Ca(2+) homeostasis.|||Membrane|||Mitochondrion membrane|||Palmitoylated by ZDHHC16, promoting formation of the homopentamer.|||Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes (By similarity). Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated calcium uptake.|||Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation (PubMed:22971924, PubMed:26816378). Controls intracellular Ca(2+) levels in elongated spermatids. May play a role in germ cell differentiation (PubMed:30733280).|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Meak7 ^@ http://purl.uniprot.org/uniprot/Q8K0P3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Activates an alternative mTOR signaling through RPS6KB2 activation and EIF4EBP1 repression to regulate cell proliferation and migration. Recruits MTOR at the lysosome, essential for MTOR signaling at the lysosome.|||Cytoplasm|||Interacts (via C-terminal domain) with MTOR and MLST8; the interaction with MTOR increases upon nutrient stimulation.|||Lysosome|||Membrane http://togogenome.org/gene/10090:V1rd19 ^@ http://purl.uniprot.org/uniprot/Q3KNP5 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Mmp17 ^@ http://purl.uniprot.org/uniprot/Q9R0S3 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumor necrosis factor-alpha. May also be involved in tumoral process. Not obvious if able to proteolytically activate progelatinase A. Does not hydrolyze collagen types I, II, III, IV and V, gelatin, fibronectin, laminin, decorin nor alpha1-antitrypsin.|||Expressed by monocytes and macrophages.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||extracellular matrix http://togogenome.org/gene/10090:Zmat4 ^@ http://purl.uniprot.org/uniprot/Q8BZ94 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Acot10 ^@ http://purl.uniprot.org/uniprot/Q32MW3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the acyl coenzyme A hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Active on long chain acyl-CoAs.|||Mitochondrion http://togogenome.org/gene/10090:Ccdc13 ^@ http://purl.uniprot.org/uniprot/D3YV10 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with PCM1, CEP290 and PCNT.|||Required for primary cilia formation and promotes the localization of the ciliopathy protein BBS4 to both centriolar satellites and cilia.|||centriolar satellite|||cilium basal body http://togogenome.org/gene/10090:Gpx7 ^@ http://purl.uniprot.org/uniprot/Q3TNK3|||http://purl.uniprot.org/uniprot/Q99LJ6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glutathione peroxidase family.|||It protects esophageal epithelia from hydrogen peroxide-induced oxidative stress. It suppresses acidic bile acid-induced reactive oxygen species (ROS) and protects against oxidative DNA damage and double-strand breaks (By similarity).|||Secreted http://togogenome.org/gene/10090:Cyp2c40 ^@ http://purl.uniprot.org/uniprot/E9Q7C8|||http://purl.uniprot.org/uniprot/P56657 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that may play a major role in the metabolism of arachidonic acid in the intestinal tract (PubMed:10908295, PubMed:9721182). Exhibits regioselective hydroxylase and epoxidase activity toward arachidonic acid, producing 16(R)-hydroxyeicosatetraenoic acid (HETE) and (14R,15S)-epoxyeicosatrienoic acid (EpETrE) as major products (PubMed:10908295). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:10908295).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Liver, brain, kidney, and intestine, with trace amounts in lung and heart (PubMed:9721182, PubMed:10908295). Expressed throughout the intestinal tract, with higher expression levels in jejunum, cecum and colon (PubMed:10908295).|||Microsome membrane http://togogenome.org/gene/10090:Chchd4 ^@ http://purl.uniprot.org/uniprot/Q8VEA4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes (PubMed:26004228). Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17, COX19, MICU1 and COA7. Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Required for the import of COA7 in the IMS. Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS. Reduced CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system. Mediates formation of disulfide bond in MICU1 in the IMS, promoting formation of the MICU1-MICU2 heterodimer that regulates mitochondrial calcium uptake.|||Forms intrachain disulfide bridges, but exists in different redox states.|||Mitochondrion intermembrane space|||Monomer. Can form homooligomers. Interacts with GFER and forms transient disulfide bonds with GFER. Interacts with MICU1. Interacts with COX19 forming transient intermolecular disulfide bridges. Interacts with COA7 through transient intermolecular disulfide bonds. Interacts with AIFM1; the interaction increases in presence of NADH. Interacts with NDUFB10.|||Mutants have a developmental arrest coupled with embryonic lethality at 8.5 dpc. They show a major defect in the expression of respiratory chain complex I subunit NDUFS7/CI-20.|||The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria.|||Widely expressed. Present at high level in liver and kidney, followed by lung, brain, heart and spleen (at protein level). http://togogenome.org/gene/10090:Ifng ^@ http://purl.uniprot.org/uniprot/A0A7R8C347|||http://purl.uniprot.org/uniprot/P01580 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type II (or gamma) interferon family.|||Deletion mutant mice show no special developmental defects, and their immune system appear to develop normally. However, they show susceptibility to bacterial or viral infections such as vaccinia virus or Theiler's murine encephalomyelitis virus, despite normal cytotoxic and T-helper cell responses.|||Homodimer.|||Homodimer. Interacts with IFNGR1 (via extracellular domain); this interaction promotes IFNGR1 dimerization.|||Released primarily from activated T lymphocytes.|||Secreted|||Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:8456301, PubMed:11585387). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (By similarity). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (PubMed:20535209, PubMed:25078851).|||Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL. Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation. http://togogenome.org/gene/10090:Septin1 ^@ http://purl.uniprot.org/uniprot/D3Z3V3|||http://purl.uniprot.org/uniprot/P42209 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential).|||Midbody|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation (By similarity). Interacts with AURKB (By similarity).|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Galp ^@ http://purl.uniprot.org/uniprot/Q810H5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the galanin family.|||Cleavage of the signal peptide generates a peptide of 25 amino acids, termed alarin because of the N-terminal alanine and the C-terminal serine. Vasoactive peptide.|||Exhibits antimicrobial activity against Gram-negative bacterias, inducing bacterial membrane blebbing (By similarity). Exhibits potent and dose-dependent vasoconstrictor and anti-edema activity in the cutaneous microvasculature, a physiologic effects which does not appear to be mediated via GALR1 or GALR2.|||Hypothalamic neuropeptide which binds to the G-protein-coupled galanin receptors (GALR1, GALR2 and GALR3). Involved in a large number of putative physiological functions in CNS homeostatic processes, including the regulation of gonadotropin-releasing hormone secretion.|||Isoform 2 is found in brain, thymus and skin. Isoform 2 is found in the skin, in pericytes covering microvascular arterioles and venules on their abluminal surfaces. In larger vessels, isoform 2 is expressed in layers of smooth muscle cells. Isoform 2 is not detected in endothelial cells.|||Secreted http://togogenome.org/gene/10090:Tiam2 ^@ http://purl.uniprot.org/uniprot/Q6ZPF3 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TIAM family.|||Cytoplasm|||Expressed in cerebral cortex, predominantly in the cortical plate and intermediate zone and weakly in the ventricular zone, in neurites and the growth cone of neurites of the hippocampus at 15 dpc (at protein level). Expressed in embryo at 7, 11, 15 and 17 dpc. Expressed in the preplate which consists of the Cajal-Retzius cells and the precursors of subplate neurons, in neurons of the telecephalon, in primordia of cerebral cortex and hippocampus at 12 dpc. Expressed in the cortical plate, striatum and fourth ventricle of the brain, in the cartilaginous tissues including Meckel, costal, vertebral and tracheal cartilage at 14.5 dpc. Expressed in cerebral cortex, hippocampus, olfactory bulbs, rostral migratory pathway and the striatum at 17 dpc.|||Expressed in fetal brain (at protein level). Expressed in the olfactory bulb, cortical plate of the cerebral cortex, caudate putamen, hippocampus, ependymal cells of the lateral surface of the lateral ventricles of the brain. Weakly expressed in heart, lung, liver, skeletal muscle, kidney and testis.|||Interacts with MAP1A, MAP1B, PARP1 and YWHAE. Interacts with CD44, PARD3 and MAPK8IP2.|||Modulates the activity of RHO-like proteins and connects extracellular signals to cytoskeletal activities. Acts as a GDP-dissociation stimulator protein that stimulates the GDP-GTP exchange activity of RHO-like GTPases and activates them. Activates specifically RAC1, but not CDC42 and RHOA. Mediates extracellular laminin signals to activate Rac1, contributing to neurite growth. Involved in lamellipodial formation and advancement of the growth cone of embryonic hippocampal neurons. Promotes migration of neurons in the cerebral cortex. When overexpressed, induces membrane ruffling accompanied by the accumulation of actin filaments along the altered plasma membrane.|||Perikaryon|||Phosphorylated on serine and threonine residues. Phosphorylated on Thr-1662 by Rho-kinase. Its phosphorylation by Rho-kinase inhibits its guanine nucleotide exchange activity, its interaction with MAP1A, MAP1B, PARP1 and YWHAE and reduces its ability to promote neurite growth.|||The PH 1 domain and amino acids 619-780 (a region called TSS; otherwise known as CC-Ex) are necessary for membrane localization. PH 1 and TSS domains are necessary for Rac1 activity. The PH 2 domain is engaged in the enhancement of the catalytic activity of the adjacent DH domain. The PH 1, TSS and DH domains are necessary to induce neurite-like structure.|||filopodium|||growth cone|||lamellipodium|||neuron projection http://togogenome.org/gene/10090:Or7e178 ^@ http://purl.uniprot.org/uniprot/Q0VAX9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Dll1 ^@ http://purl.uniprot.org/uniprot/Q61483 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Cleaved by MMP14; negatively regulates DLL1-induced Notch signaling in HPCs, modulating B-lymphocyte differentiation in bone marrow (PubMed:21572390). Undergoes two consecutive processing events: a shedding event, partially by ADAM10, that generates a soluble extracellular form and an intracellular membrane-anchored form, followed by a gamma-secretase cleavage releasing an intracellular fragment (PubMed:12794186).|||Expressed until 15 dpc. Expression then decreases and increases again in the adult. In differentiating somites, is expressed at low levels in cells emerging from the dorsomedial lip and subsequently throughout myotomes. In the limb buds, is found in myoblasts and myocytes but not in the progenitor cells (PubMed:17194759). Highly expressed in the endothelium and in the smooth muscle layer starting at 13.5 dpc in arterial vessels, but not in veins. At 12.5 dpc, there is no detectable expression in arteries or veins. This pattern persists until 18.5 dpc (PubMed:19144989). Strongly expressed in developing muscle of tongue, cheek, and in extraocular muscle at 11.5 dpc. Found at 18 dpc and P21 in head muscle (PubMed:25220152). Detected in a subset of cells in the ventricular zone (VZ), the intermediate zone (IZ) and the cortical plate (CP) of neocortex and in the ganglionic eminences at 13.5 dpc. At later stages, such as at 16.5 dpc, found in the VZ and IZ, but at very low levels in the CP of the neocortex (PubMed:18997111). Highly expressed in embryonic cells located in the ventricular zone (VZ) of the retinal neuroepithelium that form clusters; is first detected in cells located in the central retina. As the retina grows, expression spreads peripherally along the expanding neurogenic region, being always absent from the ciliary margin zone (CMZ) (PubMed:19389377).|||Heterozygous Dll1 mice mutants are lighter and smaller, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood (PubMed:19562077). Heterozygous Dll1 mice mutants and hypomorphic Dll1 mice mutants survive until birth, despite significantly reduced Notch activity (PubMed:17194759). Conditional knockout in inner ear leads to an early and excessive production of hair cells and have vestibular defects (PubMed:16495313). Conditional knockout in a small proportion of neural precursor cells reduces neurogenesis, whereas conditional knockout in a large proportion promotes premature neurogenesis (PubMed:18997111). Hypomorph Dll1 pups mutant survive until birth but are smaller. Conditional knockout Dll1 mice mutant in epidermis, survive and have no gross abnormalities (PubMed:17960184). Hypomorph Dll1 mice mutant survive until birth and have severe skeletal muscle defects (PubMed:19144989). Heterozygous Dll1 mutant embryos show disrupted muscle growth (PubMed:25220152). Conditional knockout Dll1 mice mutant show disorganization of Bergmann fibers, ectopic localization of Bergmann glia in the molecular layer and a reduction in the number of Bergmann glia (PubMed:23688253).|||Homodimer (PubMed:12794186). Interacts with TJP1 (PubMed:24715457). Interacts with MMP14; inhibits DLL1-induced Notch signaling (PubMed:21572390). Interacts with MAGI1 (via PDZ domain); forms a complex with CTNNB1 and CDH2 and promotes recruitment to the adherens junction and stabilization on the cell surface (PubMed:15908431). Interacts with PSEN1; undergoes a presenilin-dependent gamma-secretase cleavage that releases a Dll1-intracellular form (PubMed:12794186). Interacts with MFAP5 (PubMed:15788413). Interacts with MIB1 (PubMed:21985982). Interacts with NEURL1B; leads to ubiquitination (PubMed:17003037, PubMed:19723503). Interacts with NEURL1 (PubMed:19723503). Interacts with SYNJ2BP; enhances DLL1 protein stability, and promotes Notch signaling in endothelial cells (By similarity). Interacts with MAGI1, MAGI2, MAGI3 and MPDZ (By similarity). Interacts (via ubiquitin) with EPN1 (via IUM domain); binding with NOTCH1 attached to neighboring cell, promotes ligand ubiquitination and EPN1 interaction, leading to NECD transendocytosis and Notch signaling. Interacts with NOTCH1 (By similarity).|||In the embryo, expressed in the paraxial mesoderm and nervous system. Expressed at high levels in adult heart and at lower levels, in adult lung. Highly expressed in satellite cells from masseter and tongue than in satellite cells from leg and extraocular muscle.? (PubMed:25220152).|||Induced by PTF1A in multipotent pancreatic progenitor cells (PubMed:22096075). Induced by CDX1 and CDX2 during somitogenesis and goblet cell differentiation (PubMed:22015720).|||Membrane raft|||Nucleus|||O-fucosylated. Can be elongated to a disaccharide by MFNG.|||Phosphorylated in a membrane association-dependent manner. Phosphorylation at Ser-696 requires the presence of Ser-693, whereas phosphorylation at Thr-638 and Ser-693 occurs independently of the other sites. Phosphorylation is required for full ligand activity in vitro and affects surface presentation, ectodomain shedding, and endocytosis.|||Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner (PubMed:21985982, PubMed:10958687). Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD) (PubMed:10958687, PubMed:18676613). Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation (PubMed:17194759, PubMed:19562077, PubMed:18997111, PubMed:23695674, PubMed:16495313, PubMed:21238454, PubMed:22282195, PubMed:7671806, PubMed:17960184, PubMed:22529374, PubMed:19389377, PubMed:23699523, PubMed:19144989, PubMed:23688253, PubMed:23806616, PubMed:26114479, PubMed:22940113, PubMed:25220152, PubMed:20081190, PubMed:21572390, PubMed:22096075). Plays a role in brain development at different level, namely by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner (PubMed:7671806, PubMed:18997111). During neocortex development, Dll1-Notch signaling transmission is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia; the cell-cell interactions are mediated via dynamic and transient elongation processes, likely to reactivate/maintain Notch activity in neighboring progenitors, and coordinate progenitor cell division and differentiation across radial and zonal boundaries (PubMed:23699523). During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway (PubMed:23688253). At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway (PubMed:19389377, PubMed:26114479). Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis (PubMed:20081190). Maintains quiescence of neural stem cells and plays a role as a fate determinant that segregates asymmetrically to one daughter cell during neural stem cells mitosis, resulting in neuronal differentiation in Dll1-inheriting cell (PubMed:23695674). Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B cells (PubMed:15146182, PubMed:19217325). Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor (By similarity). Upon MMP14 cleavage, negatively regulates Notch signaling in haematopoietic progenitor cells to specifically maintain normal B-cell development in bone marrow (PubMed:21572390). Also plays a role during muscle development. During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation (PubMed:17194759). Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling. Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression (PubMed:22940113). During craniofacial and trunk myogenesis suppresses differentiation of cranial mesoderm-derived and somite-derived muscle via MYOD1 regulation but in cranial mesoderm-derived progenitors, is neither required for satellite cell homing nor for PAX7 expression (PubMed:25220152). Also plays a role during pancreatic cell development. During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium (PubMed:22529374). Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels (PubMed:22096075). During fetal stages of development, is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression (PubMed:19144989). Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation (PubMed:22282195). Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine (PubMed:21238454, PubMed:21915337). Plays a role during inner ear development; negatively regulates auditory hair cell differentiation (PubMed:16495313). Plays a role during nephron development through Notch signaling pathway (PubMed:23806616). Regulates growth, blood pressure and energy homeostasis (PubMed:19562077).|||Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation. Ubiquitinated; promotes recycling back to the plasma membrane and confers a strong affinity for NOTCH1 (PubMed:18676613). Multi-ubiquitination of Lys-613 by MIB1 promotes both cis and trans-interaction with NOTCH1, as well as activation of Notch signaling (PubMed:21985982). Ubiquitinated by NEURL1B (PubMed:17003037).|||adherens junction http://togogenome.org/gene/10090:Btbd6 ^@ http://purl.uniprot.org/uniprot/Q8K2J9 ^@ Function|||Subcellular Location Annotation ^@ Adapter protein for the cul3 E3 ubiquitin-protein ligase complex (By similarity). Involved in late neuronal development and muscle formation (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Kpna6 ^@ http://purl.uniprot.org/uniprot/O35345|||http://purl.uniprot.org/uniprot/Q8BH30 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the importin alpha family.|||Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.|||Cytoplasm|||Forms a complex with importin subunit beta-1 (By similarity). Interacts with ZIC3.|||Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.|||Functions in nuclear protein import.|||Only slightly detected in Ehrlich ascites tumor cells, thymus and skeletal muscle, clearly detected in kidney, spleen, liver, heart, and lung. High expression in testis.|||The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity).|||The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity). http://togogenome.org/gene/10090:Dpep3 ^@ http://purl.uniprot.org/uniprot/Q9DA79 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:12738806, exhibits dipeptidase activity hydrolyzing cystinyl-bis-glycine but according to PubMed:32325220, lacks this activity which may be due to the inability of serine (instead of aspartate found in DPEP1/2) at position 356 to function as the acid/base catalyst and activate the nucleophilic water/hydroxide.|||Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.|||Expressed in ovary and testis at 15.5 dpc.|||Expressed in testis but not ovary.|||Homodimer; disulfide-linked (By similarity). Interacts with TEX101; co-localized on the cell surface of spermatocytes, spermatids, and testicular spermatozoa, co-localized only in cytoplasmic droplets of caput and corpus epididymal sperm (PubMed:21724266).|||Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine (PubMed:32325220). The absence of activity may be due to the inability of serine (instead of aspartate found in DPEP1/2) at position 356 to function as the acid/base catalyst and activate the nucleophilic water/hydroxide (PubMed:32325220). Does not hydrolyze leukotriene D4 (LTD4) into leukotriene E4 (LTE4) (PubMed:12738806). Does not hydrolyze the beta-lactam antibiotic imipenem (By similarity).|||Membrane|||No visible phenotype. Mice are fertile despite a significant reduction in sperm count. http://togogenome.org/gene/10090:Polr1f ^@ http://purl.uniprot.org/uniprot/B2RT77|||http://purl.uniprot.org/uniprot/Q78WZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic RPA43 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (By similarity). Interacts with RRN3/TIF-IA.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors. Through its association with RRN3/TIF-IA may be involved in recruitment of Pol I to rDNA promoters.|||DNA-dependent RNA polymerase which catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.|||Widely expressed.|||nucleolus http://togogenome.org/gene/10090:Mecom ^@ http://purl.uniprot.org/uniprot/P14404 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Both zinc finger regions are required for the transcriptional activation of PBX1.|||Cytoplasm|||Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 'Lys-9' trimethylation. Likely to be one of the primary histone methyltransferases along with PRDM16 that direct cytoplasmic H3K9me1 methylation.|||Expressed at 8.5 dpc in the anterior section of the primary head folds. Ubiquitously expressed at 9.5 dpc with higher expression in forebrain, mesenchyme of the branchial arches, nasal pits, limb buds and mesonephric ducts. Also detected at 10.5 dpc in hindbrain and lateral region of the neural tube.|||Functions as a transcriptional regulator binding to DNA sequences in the promoter region of target genes and regulating positively or negatively their expression. Oncogene which plays a role in development, cell proliferation and differentiation. May also play a role in apoptosis through regulation of the JNK and TGF-beta signaling. Involved in hematopoiesis.|||Homooligomer. Interacts with CTBP1. Interacts with SMAD3 (via MH2 domain); the interaction is direct. Interacts with SMAD4; through interaction with SMAD3. Interacts with CREBBP, KAT2B and histone deacetylases. Interacts with MAPK8 and MAPK9; inhibits JNK signaling (By similarity). Interacts with SUV39H1 (via SET domain); enhances MECOM transcriptional repression activity.|||May be acetylated by CREBBP and KAT2B.|||Mice develop until 9.5 dpc but die before 11.5 dpc. At 10.5 dpc embryos display multiple malformations associated with hypocellularity and reduced body size. Required for neural, heart and paraxial mesenchyme.|||Nucleus|||Nucleus speckle|||Produced by alternative promoter usage. May be due to intron retention. http://togogenome.org/gene/10090:Or8g34 ^@ http://purl.uniprot.org/uniprot/Q9EQB6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Evi2 ^@ http://purl.uniprot.org/uniprot/Q8VD58 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in myeloid and lymphoid progenitors and increased in mature hematopoietic populations with the highest levels in granulocytes.|||Membrane|||Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells. http://togogenome.org/gene/10090:Bclaf1 ^@ http://purl.uniprot.org/uniprot/A0A087WQA0|||http://purl.uniprot.org/uniprot/F8WI22|||http://purl.uniprot.org/uniprot/Q8K019 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BCLAF1/THRAP3 family.|||Citrullinated by PADI4.|||Cytoplasm|||Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA (By similarity).|||Interacts with Bcl-2 related proteins, EMD, with the adenovirus E1B 19 kDa protein and with DNA. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN (By similarity). Component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, KIAA1429, RBM15, BCLAF1 and THRAP3 (By similarity).|||Nucleus|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Cyp2j12 ^@ http://purl.uniprot.org/uniprot/G3UXT0 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Psma1 ^@ http://purl.uniprot.org/uniprot/Q3TS44|||http://purl.uniprot.org/uniprot/Q9R1P4 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||C-terminal extension is partially cleaved off by limited proteolysis leading to a conversion of the proteasome from its latent into its active form.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966). Interacts with NOTCH3 (By similarity). Interacts with ZFAND1 (By similarity).|||Up-regulated in liver tumor tissues. Up-regulated by the antioxidant dithiolethione (D3T) in liver, lung and colon (at the protein level). http://togogenome.org/gene/10090:Lipc ^@ http://purl.uniprot.org/uniprot/P27656|||http://purl.uniprot.org/uniprot/Q3TYU0 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (FFA) and smaller lipoprotein particles (By similarity). Also exhibits lysophospholipase activity (By similarity). Can hydrolyze both neutral lipid and phospholipid substrates but shows a greater binding affinity for neutral lipid substrates than phospholipid substrates (By similarity). In native LDL, preferentially hydrolyzes the phosphatidylcholine species containing polyunsaturated fatty acids at sn-2 position (By similarity).|||Homodimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Krtap3-1 ^@ http://purl.uniprot.org/uniprot/A2A591 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 3 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).|||Interacts with hair keratins. http://togogenome.org/gene/10090:Acta1 ^@ http://purl.uniprot.org/uniprot/P68134 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.|||Belongs to the actin family.|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Methylated at His-75 by SETD3.|||Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.|||N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.|||Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others (By similarity). Interacts with alpha-actinin. Identified in a complex composed of ACTA1, COBL, GSN AND TMSB4X (By similarity). Interacts with TTID. Interacts (via its C-terminus) with USP25 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Grhl1 ^@ http://purl.uniprot.org/uniprot/E9QMF0|||http://purl.uniprot.org/uniprot/Q921D9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15.5 dpc isoform 1 is expressed predominantly in the skin and in the developing hair germ, isoform 2 is expressed predominantly in the epidermis.|||Belongs to the grh/CP2 family. Grainyhead subfamily.|||Binds DNA as homodimer. Homodimer, also forms heterodimers with GRHL2 or GRHL3.|||GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxical lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.|||Isoform 1 is highly expressed in brain, pancreas, tonsil, placenta and kidney. Isoform 2 is highly expressed in brain and liver. Expression in the skin is confined to the suprabasal layers of the epidermis and to the hair follicles.|||Methylation at Arg-9 and Lys-116 may be involved in regulating transcriptional activation.|||Mutants are healthy and fertile, but display an initial delay in coat growth, with older mice exhibiting hair loss as a result of poor anchoring or the hair shaft in the follicle. They show reduced numbers of abnormal desmosomes in the interfollicular epidermis. Develop palmoplantar keratoderma (PubMed:21081122). They also exhibit mild chronic skin barrier defects with altered keratinocyte terminal differentiation, increased expression of inflammatory markers and infiltration of the skin by immune cells.|||Nucleus|||Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:18288204, PubMed:21081122). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier (PubMed:18288204, PubMed:24586629). There is no genetic interaction with GRHL3, nor functional cooperativity due to diverse target gene selectivity during epithelia development (PubMed:21081122). May play a role in regulating glucose homeostasis and insulin signaling. http://togogenome.org/gene/10090:Klre1 ^@ http://purl.uniprot.org/uniprot/Q8CJC7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in natural killer (NK) cells (at protein level) (PubMed:12782717, PubMed:14707119, PubMed:12715246). Also detected in natural killer T (NKT) cells (at protein level) (PubMed:14707119, PubMed:12715246). Has little or no expression in T cells (at protein level) (PubMed:14707119, PubMed:12715246).|||Heterodimer; with KLRI1 or KLRI2.|||Lectin-like receptor for natural killer (NK) cells (PubMed:14707119, PubMed:15069013, PubMed:18713988). Can either inhibit or activate NK cell cytotoxic activity, depending on its binding partner (PubMed:14707119, PubMed:15069013, PubMed:18713988). Heterodimer formation with KLRI1 mediates NK cell inhibition whereas heterodimer formation with KLRI2 mediates NK cell activation (PubMed:18713988). Plays a role in allogeneic recognition by the immune system (PubMed:14707119, PubMed:15069013).|||Viable and fertile, with no gross abnormalities. Development of natural killer (NK) cells appears to be normal. Cytolytic activity of activated NK cells against allogeneic target cells is significantly reduced. http://togogenome.org/gene/10090:Tpra1 ^@ http://purl.uniprot.org/uniprot/Q99MU1 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UPF0359 family.|||Induced during adipocytes differentiation and in white fat from aged and diabetics mice.|||Membrane|||Ubiquitous, with higher levels in heart, brain, lung, liver and kidney. http://togogenome.org/gene/10090:Pds5b ^@ http://purl.uniprot.org/uniprot/F8WHU5|||http://purl.uniprot.org/uniprot/Q4VA53 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDS5 family.|||Expressed in prostate.|||Interacts with the cohesin complex. Interacts with RAD21; the interaction is direct. Interacts with WAPL (via FGF motifs) or CDCA5 (via the FGF motif); the interaction is direct, cohesin-dependent and competitive (By similarity).|||Nucleus|||Regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Plays a role in androgen-induced proliferative arrest in prostate cells (By similarity). http://togogenome.org/gene/10090:Catspere2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXX9 ^@ Caution|||Similarity ^@ Although related to the CATSPERD family, it is unclear whether the protein is part of a Catsper complex.|||Belongs to the CATSPERD family. http://togogenome.org/gene/10090:Sdhb ^@ http://purl.uniprot.org/uniprot/Q9CQA3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.|||Binds 1 [2Fe-2S] cluster.|||Binds 1 [3Fe-4S] cluster.|||Binds 1 [4Fe-4S] cluster.|||Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD (By similarity). Interacts with SDHAF1; the interaction is required for iron-sulfur cluster incorporation into SDHB (By similarity).|||Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Rcan1 ^@ http://purl.uniprot.org/uniprot/Q542V6|||http://purl.uniprot.org/uniprot/Q9JHG6 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RCAN family.|||Highly expressed in heart and skeletal muscle. Also expressed in all other tissues.|||Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development (PubMed:11231093).|||Interacts with RAF1 and PPP3R1 (By similarity). Interacts with PPP3CA (PubMed:12809556).|||Phosphorylation increases its ability to inhibit calcineurin and decreases protein half-life. http://togogenome.org/gene/10090:Tnfrsf1b ^@ http://purl.uniprot.org/uniprot/P25119|||http://purl.uniprot.org/uniprot/Q545P4 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds to TRAF2. Interacts with BMX. Interacts (activated form) with XPNPEP3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor with high affinity for TNFSF2/TNF-alpha and approximately 5-fold lower affinity for homotrimeric TNFSF1/lymphotoxin-alpha. The TRAF1/TRAF2 complex recruits the apoptotic suppressors BIRC2 and BIRC3 to TNFRSF1B/TNFR2 (By similarity). http://togogenome.org/gene/10090:4921524J17Rik ^@ http://purl.uniprot.org/uniprot/Q9CR55 ^@ Similarity ^@ Belongs to the UPF0547 family. http://togogenome.org/gene/10090:Mbd3l1 ^@ http://purl.uniprot.org/uniprot/Q9D9H3 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MBD3L family.|||Does not bind methylated DNA.|||Highly expressed in testis. Not detected in the other tissues tested.|||Nucleus|||The N-terminal half of the protein mediates transcription repression.|||Transcriptional repressor. http://togogenome.org/gene/10090:Lrch3 ^@ http://purl.uniprot.org/uniprot/Q8BVU0 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton.|||Component of the DOCK7-induced septin displacement/DISP complex, at least composed of DOCK7, LRCH3 and MYO6.|||Cytoplasm|||Predicted to contain a signal peptide and to be secreted. However, this is not consistent with an interaction with DOCK7 and MYO6 and the suggested function in cytoskeleton organization. http://togogenome.org/gene/10090:Syn2 ^@ http://purl.uniprot.org/uniprot/Q64332|||http://purl.uniprot.org/uniprot/Q8CE19 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synapsin family.|||Can form oligomers with SYN1 (By similarity). Interacts with CAPON.|||Expressed exclusively in neuronal cells. Isoform IIb is enriched in sympathetic cervical ganglion.|||Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. May play a role in noradrenaline secretion by sympathetic neurons.|||Phosphorylation at Ser-10 dissociates synapsins from synaptic vesicles (By similarity). Phosphorylation at Ser-426 by MAPK1/ERK2 and/or MAPK3/ERK1 may play a role in noradrenaline secretion by sympathetic neurons.|||Synapse|||The A region binds phospholipids with a preference for negatively charged species. http://togogenome.org/gene/10090:Gimap9 ^@ http://purl.uniprot.org/uniprot/G3X987|||http://purl.uniprot.org/uniprot/Q8BYB6 ^@ Sequence Caution|||Similarity|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.|||Contaminating sequence. Potential poly-A sequence.|||Expressed in thymus (in thymocytes), spleen (in splenocytes), lymph node and lung. http://togogenome.org/gene/10090:Gss ^@ http://purl.uniprot.org/uniprot/P51855|||http://purl.uniprot.org/uniprot/Q3UEE2|||http://purl.uniprot.org/uniprot/Q541E2 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the eukaryotic GSH synthase family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. Glutathione (gamma-glutamylcysteinylglycine, GSH) is the most abundant intracellular thiol in living aerobic cells and is required for numerous processes including the protection of cells against oxidative damage, amino acid transport, the detoxification of foreign compounds, the maintenance of protein sulfhydryl groups in a reduced state and acts as a cofactor for a number of enzymes. Participates in ophthalmate biosynthesis in hepatocytes (PubMed:16608839).|||Homodimer. http://togogenome.org/gene/10090:Rabepk ^@ http://purl.uniprot.org/uniprot/Q8VCH5 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endosome membrane|||Interacts with PIKFYVE; the interaction recruits RABEPK to the endosomal membrane (PubMed:14530284). Interacts with RAB9 in its GTP-bound conformation (By similarity).|||It is uncertain whether Met-1 or Met-9 is the initiator.|||Phosphorylated on Ser residues by PIKFYVE.|||Rab9 effector required for endosome to trans-Golgi network (TGN) transport. http://togogenome.org/gene/10090:Cyb5b ^@ http://purl.uniprot.org/uniprot/Q9CQX2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome b5 family.|||Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MTARC2.|||Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Ssr1 ^@ http://purl.uniprot.org/uniprot/Q9CY50 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAP-alpha family.|||Endoplasmic reticulum membrane|||Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma. Interacts with palmitoylated calnexin (CALX), the interaction is required for efficient folding of glycosylated proteins (By similarity).|||Seems to bind calcium.|||Shows a remarkable charge distribution with the N-terminus being highly negatively charged, and the cytoplasmic C-terminus positively charged.|||TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocation apparatus after completion of the translocation process or may function as a membrane-bound chaperone facilitating folding of translocated proteins. http://togogenome.org/gene/10090:Kiss1 ^@ http://purl.uniprot.org/uniprot/Q6Y4S4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Animals are viable and healthy with no apparent abnormalities but fail to undergo sexual maturation. Mutant female do not progress through the estrous cycle, have thread-like uteri and small ovaries, and do not produce mature Graffian follicles. Mutant males have small testes, and spermatogenesis arrested mainly at the early haploid spermatid stage. Both sexes have low circulating gonadotropin (LH and FSH) and sex steroid (beta-estradiol or testosterone) hormone levels. Migration of GnRH neurons into the hypothalamus appears normal with appropriate axonal connections to the median eminence and total GnRH content. The hypothalamic-pituitary axis is functional, as shown by robust LH secretion after peripheral administration of kisspeptin.|||Belongs to the KISS1 family.|||Metastasis suppressor protein. May regulate events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-terminally amidated peptide, metastin which functions as the endogenous ligand of the G-protein coupled receptor GPR54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. The receptor is also essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. Intracerebroventricular administration induces an increase in serum LH and FSH levels in prepubertal male and female as well as in adult animals.|||Secreted|||Weak in all tissue types with highest levels in lung and 15- 17-day embryos. Expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. http://togogenome.org/gene/10090:Ppy ^@ http://purl.uniprot.org/uniprot/P10601|||http://purl.uniprot.org/uniprot/Q496X5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NPY family.|||Hormone secreted by pancreatic cells that acts as a regulator of pancreatic and gastrointestinal functions probably by signaling through the G protein-coupled receptor NPY4R2.|||No icosapeptide-like peptide is cleaved from the C-terminal.|||Secreted http://togogenome.org/gene/10090:Cftr ^@ http://purl.uniprot.org/uniprot/P26361 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.|||Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains (By similarity). The first ABC transporter nucleotide-binding domain has no ATPase activity by itself (PubMed:14685259, PubMed:15619636).|||Cell membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:20231442, PubMed:22265409). Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1 (By similarity). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:21976599).|||Expressed in the epididymis (at protein level) (PubMed:30659401). In the initial segment of the epididymis, detected on both the luminal and basolateral sides of the ducts where it is expressed in the duct columnar cells as well as in the interstitial smooth muscle cells (PubMed:30659401). Expressed in sperm in the caput (PubMed:30659401). In the cauda, detected along the luminal border but not continuously and is also expressed on the basolateral surface (PubMed:30659401). Within the caudal lumen, detected on sperm (PubMed:30659401). Isoform 1: Expressed in a variety of epithelial tissues including colon, kidney, lung, small intestine, pancreatic duct and testis (PubMed:7691356). Isoform 2: Expressed only in testis (PubMed:7691356). Isoform 3: Expressed only in testis (PubMed:7691356).|||Mice are born at the expected Mendelian rate, but about 80% die within two to five days after birth due to peritonitis (PubMed:7685652). Those that survive fail to thrive, appear runted and weigh about half as much as wild-type littermates (PubMed:7685652). Many of the surviving pups die when they start ingesting solid food, due to intestinal blockage caused by excessive mucus accumulation (PubMed:7685652). None survive for more than about 45 days after birth (PubMed:7685652). Intestinal crypts in the jejunum and ileum are filled with excessive mucus (PubMed:7685652). Excessive accumulation of mucus is also seen in colon (PubMed:7685652). In contrast, their lungs do not present pathological mucus accumulation (PubMed:7685652). Likewise, only five out of ten animals show dilatation and blockage of several small pancreatic ducts (PubMed:7685652). Besides, mutant mice present defects in their lacrimal glands that make them more susceptible to develop eye infections (PubMed:7685652). In caecum epithelium, forskolin-sensitive ion transport is nearly abolished (PubMed:7685652).|||Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity). Interacts with SLC26A3, SLC26A6 and NHERF1 (PubMed:21976599). Interacts with SHANK2 (By similarity). Interacts with MYO6 (By similarity). Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity. Interacts with SLC4A7 through NHERF1. Found in a complex with MYO5B and RAB11A. Interacts with ANO1. Interacts with SLC26A8 (By similarity). Interacts with AHCYL1; the interaction increases CFTR activity (PubMed:19033647, PubMed:23542070). Interacts with CSE1L (By similarity). The core-glycosylated form interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER stress (By similarity). Interacts with MARCHF2; the interaction leads to CFTR ubiqtuitination and degradation (By similarity).|||N-glycosylated.|||Nucleus|||Phosphorylated; cAMP treatment promotes phosphorylation and activates the channel. Dephosphorylation decreases the ATPase activity (in vitro). Phosphorylation at PKA sites activates the channel. Phosphorylation at PKC sites enhances the response to phosphorylation by PKA. Phosphorylated by AMPK; this inhibits channel activity.|||Recycling endosome membrane|||The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, NHERF1/EBP50 complex.|||The disordered R region mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation.|||Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes enhances its endocytic recycling to the cell membrane. Ubiquitinated by RNF185 during ER stress. Ubiquitinated by MARCHF2 (By similarity). http://togogenome.org/gene/10090:Rasd1 ^@ http://purl.uniprot.org/uniprot/O35626 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. RasD family.|||By dexamethasone.|||Cell membrane|||Component of a complex, at least composed of APBB1, RASD1/DEXRAS1 and APP. Interacts with APBB1/FE65 (By similarity). Forms a ternary complex with CAPON and NOS1.|||Expressed in brain, heart, kidney and liver.|||Nucleus|||S-nitrosylation stimulates guanine-nucleotide exchange activity.|||Small GTPase. Negatively regulates the transcription regulation activity of the APBB1/FE65-APP complex via its interaction with APBB1/FE65 (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Slc22a27 ^@ http://purl.uniprot.org/uniprot/Q76M72 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Does not appear to have transporter activity.|||Expressed in proximal kidney tubules, and in liver hepatocytes (at protein level).|||Sodium-independent organic anion transporter which exhibits high specificity for L-carnitine. Can also transport salicylic acid and the drug cimetidine. http://togogenome.org/gene/10090:Prnd ^@ http://purl.uniprot.org/uniprot/Q544A3|||http://purl.uniprot.org/uniprot/Q9QUG3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A short helical region is required and sufficient for Cu(2+) binding.|||Belongs to the prion family.|||Cell membrane|||Detected in testis (PubMed:10842180, PubMed:12110578, PubMed:15161660). Detected within seminiferous tubules, on round and elongated spermatids (at protein level) (PubMed:12110578). Not detected in brain (at protein level) (PubMed:10842180, PubMed:15161660). Detected in testis, and at low levels in heart (PubMed:10525406, PubMed:12110578). Expression in brain is very low and barely detectable (PubMed:10525406).|||Expressed during embryogenesis.|||Loss of cerebellar Purkinje cells and ataxia has been observed in mice with mutations that cause Prnd overexpression in the brain, suggesting that aberrant overexpression of Prnd causes neurotoxicity.|||Membrane|||Mice are born at the expected Mendelian rate and appear grossly normal and healthy. Females are fertile, but males are almost completely sterile, in spite of normal mating behavior (PubMed:12110578, PubMed:15161660). Two independent studies conclude that male sterility is due to impaired acrosome reaction, but describe contradictory effects on spermatogenesis, possibly due to the use of different mouse strains (PubMed:12110578, PubMed:15161660). Spermatogenesis is normal, with normal sperm counts, normal sperm motility, and no malformation of the sperm head or tail (PubMed:15161660). Late stages of spermiogenesis are impaired, leading to reduced numbers of mature spermatozoa in seminiferous tubules; mutant sperm present morphological abnormalities of the flagellum and sperm head, and decreased motility (PubMed:12110578). Mutant sperm are able to fertilize oocytes in vitro, but many of the resulting embryos die before the morula stage (PubMed:15161660). Mutant sperm cells have elevated levels of DNA damage and DNA strand breaks, and this may be the cause for embryonic lethality (PubMed:15161660). Mice deficient for both Prnd and Prnp have the same phenotype as mice lacking Prnd; they are born at the expected Mendelian rate and appear grossly normal and healthy (PubMed:15161660, PubMed:15007175). Females are fertile, but males deficient for both Prnd and Prnp are sterile, in spite of normal mating behavior (PubMed:15161660, PubMed:15007175). Again, findings about spermatogenesis are contradictory: spermatogenesis is normal, with normal sperm counts, normal sperm motility, and no malformation of the sperm head or tail (PubMed:15161660). Sperm cells display various malformations (PubMed:15007175). Male sterility is due to impaired acrosome reaction (PubMed:15161660). Mutant sperm are able to fertilize oocytes in vitro, but many of the resulting embryos die before the morula stage (PubMed:15161660). Mutant sperm cells have elevated levels of DNA damage and DNA strand breaks, and this may be the cause for embryonic lethality (PubMed:15161660). Aging mice deficient for both Prnd and Prnp do not display loss of cerebellar Purkinje cells or develop ataxia, and do not develop neurological defects (PubMed:15007175).|||N-glycosylated (PubMed:10525406, PubMed:10842180). N-glycosylated at two distinct sites (PubMed:10842180).|||O-glycosylated.|||Required for normal acrosome reaction and for normal male fertility (PubMed:12110578, PubMed:15161660, PubMed:15007175). Can bind Cu(2+) (By similarity). http://togogenome.org/gene/10090:Rit1 ^@ http://purl.uniprot.org/uniprot/P70426 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alternates between an inactive form bound to GDP and an active form bound to GTP.|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Expressed in many tissues.|||Interacts with AFDN, the C-terminal domain of RALGDS and RLF, but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-bound form. Strongly interacts with BRAF, but only weakly with RAF1. BARF and RAF1 association is dependent upon the GTP-bound state (By similarity). Interacts with RGL3.|||Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation (By similarity).|||Shows rapid uncatalyzed guanine nucleotide dissociation rates, which are very much 10-fold faster than those of most Ras subfamily members.|||Stimulation of the NGF and EGF receptor signaling pathways results in rapid and prolonged activation. http://togogenome.org/gene/10090:Srf ^@ http://purl.uniprot.org/uniprot/Q9JM73 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds DNA as a multimer, probably a dimer (PubMed:15492011, PubMed:16782067). Interacts with MRTFA, forming the SRF-MRTFA nuclear complex which binds the 5'-CArG-3' consensus motif (CArG box) on DNA via SRF (PubMed:12732141, PubMed:19350017). Forms a nuclear ternary complex with MRTFA and SCAI (PubMed:19350017). Interacts with MRTFB (By similarity). Interacts with MLLT7/FOXO4, NKX3A and SSRP1 (By similarity). Interacts with ARID2 (PubMed:16782067). Interacts with SRFBP1 (PubMed:15492011). Interacts with FOXK1 (By similarity). Interacts with LPXN (By similarity). Interacts with OLFM2; the interaction promotes dissociation of SRF from the transcriptional repressor HEY2, facilitates binding of SRF to target genes and promotes smooth muscle differentiation (By similarity). Interacts with NKX3-1 (PubMed:16814806). Interacts with KAT5 (PubMed:16597624).|||Mice lacking Srf in cardiac tissue display lethal cardiac defects between 10.5 and 13.5 dpc, characterized by abnormally thin myocardium, dilated cardiac chambers, poor trabeculation and a disorganised interventricular septum.|||Nucleus|||Phosphorylated by PRKDC.|||SRF is a transcription factor that binds to the serum response element (SRE), a short sequence of dyad symmetry located 300 bp to the 5' of the site of transcription initiation of some genes (such as FOS) (PubMed:24732378). Together with MRTFA transcription coactivator, controls expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration (PubMed:12732141, PubMed:19350017, PubMed:24732378). The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics (PubMed:24732378). Required for cardiac differentiation and maturation (PubMed:15169892). http://togogenome.org/gene/10090:Prdx1 ^@ http://purl.uniprot.org/uniprot/P35700 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.|||By oxidative and sulfhydryl-reactive agents.|||Cytoplasm|||Found in various tissues; high concentration in liver.|||Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer (By similarity). Interacts with GDPD5; forms a mixed-disulfide with GDPD5 (By similarity). Interacts with SESN1 and SESN2 (By similarity). Interacts with FAM107A (PubMed:21969592).|||Mice embryos loss approximately 50% of Islet1/Islet2+ and HB9+ motor neurons, whereas dorsal-ventral patterning events and the numbers of Olig2+ progenitors are normal. Toward the end of the cell death phase they have equivalent numbers of motor neurons as wild type embryos.|||Phosphorylated on Thr-90 during the M-phase, which leads to a decrease in enzymatic activity.|||The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (By similarity). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (PubMed:19766572). http://togogenome.org/gene/10090:Dnai7 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0S9|||http://purl.uniprot.org/uniprot/Q6TDU8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNAI7 family.|||Cell cycle-dependent expression. Not detected in G0 cells, starts to accumulate in early S phase, reaches the highest level in the G2 phase, and drops to very low levels at mitosis.|||Cytoplasm|||Deficient mice display a higher susceptibility to chemical induction of lung tumors.|||High expressed in lung, kidney, and testis.|||Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains (PubMed:30060180). Interacts with tubulin (PubMed:17974961). Associates with microtubule (PubMed:17974961).|||Ubiquitinated. Ubiquitination leads to its degradation through the 26S proteasome. Ubiquitin-proteasome-mediated DNAI7 degradation occurs in mitosis.|||Via its association with the multisubunit axonemal dynein complex, is potentially involved in the regulation of cilia function (PubMed:30060180). May also act as a cell cycle regulator (PubMed:17974961).|||cilium http://togogenome.org/gene/10090:Fgf9 ^@ http://purl.uniprot.org/uniprot/A0A7U3L5J2|||http://purl.uniprot.org/uniprot/P54130 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors.|||Secreted http://togogenome.org/gene/10090:Lancl2 ^@ http://purl.uniprot.org/uniprot/Q9JJK2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LanC-like protein family.|||Cell membrane|||Cytoplasm|||Interacts with an array of inositol phospholipids such as phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 5-phosphate (PI5P). PIP-binding enhances membrane association.|||Myristoylated. Essential for membrane association.|||Necessary for abscisic acid (ABA) binding on the cell membrane and activation of the ABA signaling pathway in granulocytes.|||Nucleus http://togogenome.org/gene/10090:Slc25a24 ^@ http://purl.uniprot.org/uniprot/Q8BMD8 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport. Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple and tannic acid.|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Electroneutral antiporter that mediates the transport of adenyl nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenyl nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenyl nucleotide-dependent metabolic pathways. In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides. May play a role in protecting cells against oxidative stress-induced cell death, by buffering calcium levels in the mitochondrial matrix through the formation of calcium-phosphate precipitates.|||Linker region/H9 could directly block the transport of substrates across the transporter.|||Mitochondrion inner membrane|||Monomer.|||The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity.|||The regulatory N-terminal domain/NTD formed of two pairs of fused calcium-binding EF-hands, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity. http://togogenome.org/gene/10090:Rab3il1 ^@ http://purl.uniprot.org/uniprot/D3Z585|||http://purl.uniprot.org/uniprot/Q8VDV3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the SEC2 family.|||Guanine nucleotide exchange factor (GEF) which may activate RAB3A, a GTPase that regulates synaptic vesicle exocytosis. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. May also activate RAB8A and RAB8B (By similarity).|||Interacts with RAB3A and IHPK1 through the coiled-coil domain. This interaction is competitive. IHPK1 kinase activity is not required for this interaction (By similarity). http://togogenome.org/gene/10090:Rab3a ^@ http://purl.uniprot.org/uniprot/P63011|||http://purl.uniprot.org/uniprot/Q0PD63 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Expressed in the forebrain and hippocampus (at protein level) (PubMed:31651360). Found in active zone in brain nerve terminals (PubMed:11598194).|||Interacts with RIMS1 and RIMS2 (PubMed:11056535, PubMed:11431472, PubMed:12401793, PubMed:12578829). Interacts with Rabphilin-3A/RPH3A and Rab effector Noc2/RPH3AL (PubMed:12578829). Interacts with SYTL4 (PubMed:12590134). Interacts with RAB3IP. Interacts with SGSM1 and SGSM3 (PubMed:17509819). Interacts with SYT1 (By similarity). Interacts with MYH9; this interaction is essential for lysosome exocytosis and plasma membrane repair (By similarity). Interacts with STXBP1; this interaction promotes RAB3A dissociation from the vesicle membrane (By similarity). Interacts with SNCA (By similarity). Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (By similarity). Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (PubMed:18849981).|||Lysosome|||Phosphorylation of Thr-86 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||Postsynapse|||Presynapse|||Protein transport. Probably involved in vesicular traffic.|||RAB3-deficient mice show an incomplete and slow secretion response in brain nerve terminals after exhaustive stimulation. The replenishment of docked vesicles after exhaustive stimulation is also impaired.|||Small GTP-binding protein that plays a central role in regulated exocytosis and secretion. Controls the recruitment, tethering and docking of secretory vesicles to the plasma membrane (PubMed:11598194). Upon stimulation, switches to its active GTP-bound form, cycles to vesicles and recruits effectors such as RIMS1, RIMS2, Rabphilin-3A/RPH3A, RPH3AL or SYTL4 to help the docking of vesicules onto the plasma membrane (By similarity). Upon GTP hydrolysis by GTPase-activating protein, dissociates from the vesicle membrane allowing the exocytosis to proceed (By similarity). Stimulates insulin secretion through interaction with RIMS2 isoform RIMS2 and RPH3AL effectors in pancreatic beta cells (PubMed:15159548, PubMed:20674857). Regulates calcium-dependent lysosome exocytosis and plasma membrane repair (PMR) via the interaction with 2 effectors, SYTL4 and myosin-9/MYH9 (By similarity). Acts as a positive regulator of acrosome content secretion in sperm cells by interacting with RIMS1 (By similarity). Plays a role in the regulation of dopamine release by interacting with synaptotagmin I/SYT (By similarity).|||axon|||cytosol|||secretory vesicle http://togogenome.org/gene/10090:Utp6 ^@ http://purl.uniprot.org/uniprot/Q8VCY6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UTP6 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA.|||nucleolus http://togogenome.org/gene/10090:Col5a1 ^@ http://purl.uniprot.org/uniprot/O88207 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibrillar collagen family.|||Detected at 11 dpc, 12 dpc, 14 dpc, 16 dpc and 18 dpc. Expressed in limbs, vertebrae, heart, brain, liver, intestine, tongue, tail, skin, calvaria, lung and kidney of 18 dpc embryos (PubMed:9582436). Isoform 2 is detected at 13.5 dpc and its expression increases from 13.5 dpc to 5 weeks after birth more specially in liver, lung, ileum and heart. The expression slightly decreases after 15 weeks (PubMed:22149965).|||Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.|||Sulfated on 40% of tyrosines.|||Trimers of two alpha 1(V) and one alpha 2(V) chains in most tissues and trimers of one alpha 1(V), one alpha 2(V), and one alpha 3(V) chains in placenta. Interacts with CSPG4 (By similarity).|||Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin (By similarity). Transcriptionally activated by CEBPZ, which recognizes a CCAAT-like motif, CAAAT in the COL5A1 promoter.|||Widely expressed (PubMed:22149965). Isoform 2 is more highly expressed in liver, kidney and lung (PubMed:22149965).|||extracellular matrix http://togogenome.org/gene/10090:Eif1ad6 ^@ http://purl.uniprot.org/uniprot/Q3UT53 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Spag16 ^@ http://purl.uniprot.org/uniprot/Q8K450 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis.|||Interacts with SPAG6 and STK36.|||Necessary for sperm flagellar function. Plays a role in motile ciliogenesis. May help to recruit STK36 to the cilium or apical surface of the cell to initiate subsequent steps of construction of the central pair apparatus of motile cilia.|||Phosphorylated by TSSK2.|||cilium axoneme|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Ndufaf1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J081|||http://purl.uniprot.org/uniprot/Q9CWX2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.|||Belongs to the CIA30 family.|||Mitochondrion|||Mitochondrion matrix|||Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186. Interacts with ECSIT. Interacts with ACAD9. At early stages of complex I assembly, it is found in intermediate subcomplexes that contain different subunits including NDUFB6, NDUFA6, NDUFA9, NDUFS3, NDUFS7, ND1, ND2 and ND3. Interacts with TMEM70 and TMEM242 (By similarity). http://togogenome.org/gene/10090:Adissp ^@ http://purl.uniprot.org/uniprot/F8WIU1|||http://purl.uniprot.org/uniprot/Q9D1K7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adipocyte-secreted protein (adipokine) that acts as a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis at least in part through activation of protein kinase A (PKA).|||Adipose-specific Adissp knockout mice are defective in WAT browning, and are susceptible to high fat diet-induced obesity and hyperglycemia.|||Belongs to the ADISSP family.|||Expression is adipose-specific and highly brown adipose tissue-enriched.|||Secreted http://togogenome.org/gene/10090:Tomm34 ^@ http://purl.uniprot.org/uniprot/Q9CYG7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Tom34 family.|||Cytoplasm|||Interacts with HSP90A, VCP, ATP6V1D, KIAA0665, AMPK, and DMAP1 through its TPR repeat.|||Isoform 1 is ubiquitously expressed while isoform 2 is expressed only in mature testicular germ cells. Isoform 1 is expressed in all testicular cells. Isoform 2 is highly expressed in early to late pachytene cells but expression is significantly decreased in round spermatid cells.|||Isoform 2 is hardly detectable in testis at 1 week post partum but expression gradually increases for 2 to 4 weeks post partum. Isoform 1 is detected during this period but its expression does not change.|||Mice are viable, grow normally and both males and females are fertile. There is no effect on spermatogenesis or protein import into mitochondria.|||Mitochondrion outer membrane|||Plays a role in the import of cytosolically synthesized preproteins into mitochondria. Binds the mature portion of precursor proteins. Interacts with cellular components, and possesses weak ATPase activity. May be a chaperone-like protein that helps to keep newly synthesized precursors in an unfolded import compatible state (By similarity). http://togogenome.org/gene/10090:Ccl28 ^@ http://purl.uniprot.org/uniprot/Q9JIL2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic for resting CD4, CD8 T-cells and eosinophils (By similarity). Binds to CCR10 and induces calcium mobilization in a dose-dependent manner.|||Mainly expressed in testis, epithelial cells of normal colon, kidney, Peyer patches, lymph nodes. Also found in lower levels in brain, spleen and lung.|||Secreted http://togogenome.org/gene/10090:Qrfpr ^@ http://purl.uniprot.org/uniprot/P83861|||http://purl.uniprot.org/uniprot/Q4VA00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed widely in the brain with high levels in the cortex and hypothalamus, and moderate levels in the brain stem, caudate nucleus, midbrain hippocampus, thalamus, trigeminal ganglia and spinal cord. Particularly strong expression detected in the mitral cell layer of the olfactory bulb, accessory olfactory bulb, island of Calleja and nucleus of the solitary tract. In peripheral tissues, expressed at moderate levels in the eye, liver, kidney, pituitary gland, testis and thymus.|||Membrane|||Receptor for the orexigenic neuropeptide QRFP. The activity of this receptor is mediated by G proteins that modulate adenylate cyclase activity and intracellular calcium levels (By similarity). http://togogenome.org/gene/10090:Fut9 ^@ http://purl.uniprot.org/uniprot/O88819|||http://purl.uniprot.org/uniprot/Q14AE3 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by Mn2+.|||Belongs to the glycosyltransferase 10 family.|||Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal lactosamine unit of a glycoprotein or a glycolipid-linked polylactosamine chains through an alpha-1,3 glycosidic linkage and participates in particular to the Lewis x (Lex)/CD15 epitope biosynthesis in neurons which allows cell differentiation, cell adhesion, and initiation of neurite outgrowth (PubMed:12626397, PubMed:9756916, PubMed:15121843, PubMed:16973732). Also fucosylates di-, tri- and tetraantennary N-glycans linked to glycoproteins and the inner lactosamine unit of the alpha2,3-sialylated polylactosamine resulting in sLex (CD15s) epitope synthesis (By similarity). Furthermore, it is capable of synthesizing Lewis a (Lea), although to a lesser extent than Lex and Lewis y (Ley) and to confer SELE-dependent, but not SELL- and SELP-selectin-dependent, cell rolling and adhesion by enhancing Lex and sLex synthesis (By similarity). May also fucosylate the internal LacNAc unit of the polylactosamine chain to form VIM-2 antigen that serves as recognition epitope for SELE.|||Expressed in 1-cell embryos and then decreased dramatically in 2- and 4-cell embryos. It increases transiently in 8-cell embryos and then vanishes completely at the morula stage (PubMed:15121843). Predominantly expressed at all stages both in cerebrum and in cerebellum containing mesencephalon. Expression increases during the embryonic stage with the highest expression at P0 and decreases. Expression increases from the embryo to P7 stage, with the highest expression at P7, and decreases in adult brain. At P7 expressed in the neurons in layers II-IV and those in layers V and VI of the cerebral cortex. At P7 expressed in cerebellum, granule neurons in the internal granule cell layer (PubMed:12626397).|||Golgi apparatus membrane|||Golgi stack membrane|||Homozygous Fut9 knockout mice develop normally, with no gross phenotypic abnormalities, and are fertile.|||Mainly detected in brain and kidney.|||Membrane|||N-glycosylated with complex-type N-glycans.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Mfsd10 ^@ http://purl.uniprot.org/uniprot/Q9D2V8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily.|||Cell membrane|||Esxpressed in luminal membrane of renal tubules (PubMed:18638446). Expressed at the surface of eosinophils (at protein level) (PubMed:22820041).|||Nucleus inner membrane|||Probable organic anion transporter which may serve as a transporter for some non-steroidal anti-inflammatory drugs (NSAIDs) as well as other organic anions across the luminal membranes of renal proximal tubules at the final excretion step into the urine. http://togogenome.org/gene/10090:Tmem179 ^@ http://purl.uniprot.org/uniprot/Q8BHH9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM179 family.|||Membrane http://togogenome.org/gene/10090:Mb ^@ http://purl.uniprot.org/uniprot/P04247|||http://purl.uniprot.org/uniprot/Q3UVB1 ^@ Function|||Similarity ^@ Belongs to the globin family.|||Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. http://togogenome.org/gene/10090:Adcy10 ^@ http://purl.uniprot.org/uniprot/E9Q9T4|||http://purl.uniprot.org/uniprot/Q8C0T9 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by manganese or magnesium ions. In the presence of magnesium ions, the enzyme is activated by bicarbonate. Calcium mildly increases the enzyme activity, also in the presence of magnesium ions.|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of the signaling molecule cAMP. May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels (By similarity). Has a critical role in mammalian spermatogenesis by producing the cAMP which regulates cAMP-responsive nuclear factors indispensable for sperm maturation in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization (PubMed:14976244, PubMed:16054031). Involved in ciliary beat regulation (By similarity).|||Catalyzes the formation of the signaling molecule cAMP. May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels. Has a critical role in mammalian spermatogenesis by producing the cAMP which regulates cAMP-responsive nuclear factors indispensable for sperm maturation in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. Involved in ciliary beat regulation.|||Cell membrane|||Cytoplasm|||Expressed in testis.|||Mice are infertile because of a severe sperm-motility defect.|||Mitochondrion|||Nucleus|||The N-terminal guanylate cyclase domains are required for enzyme activity. Fragments containing the first 470 amino acid residues are fully active.|||cilium|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Maml2 ^@ http://purl.uniprot.org/uniprot/F6U238 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mastermind family.|||Nucleus speckle http://togogenome.org/gene/10090:Fcgr1 ^@ http://purl.uniprot.org/uniprot/P26151 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:11911823, mice display altered endocytosis of monomeric IgG and impaired antibody-dependent killing of cells by macrophage. Antigen presentation is also affected and those mice develop only reduced inflammatory responses. An increased in IgG responses is also detected associated with an increased number of antibody-forming cells. PubMed:11911824, also reported that a variety of IgG2a-immune complex-dependent immune functions like protection against bacterial infection were impaired.|||Belongs to the immunoglobulin superfamily. FCGR1 family.|||Cell membrane|||High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.|||Interacts with FCERG1; forms a functional signaling complex (By similarity). Interacts with FLNA; prevents FCGR1A degradation (By similarity). Interacts with EPB41L2, LAT and PPL. Interacts with HCK and LYN (By similarity).|||It is uncertain whether Met-1 or Met-10 is the initiator.|||Macrophage-specific.|||N-glycosylated.|||Phosphorylated on serine residues. http://togogenome.org/gene/10090:Rab5a ^@ http://purl.uniprot.org/uniprot/Q9CQD1 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasmic vesicle|||Early endosome membrane|||Endosome membrane|||Interacts with GDI1; this promotes dissociation from membranes; phosphorylation at Ser-84 disrupts this interaction (By similarity). Interacts with GDI2; phosphorylation at Ser-84 disrupts the interaction (By similarity). Interacts with EEA1. Interacts with RIN1 and GAPVD1, which regulate its pathway, probably by acting as a GEF. Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1. Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A chains, but at opposite sides of the dimer (By similarity). Interacts with SGSM1 and SGSM3 (PubMed:17509819). Interacts with PIK3CB (PubMed:21059846). Interacts with OCRL and INPP5F (PubMed:25869668). May be a component of a complex composed of RAB5A, DYN2 and PIK3C3 (PubMed:18425118). Does not interact with BLOC-3 complex (heterodimer of HPS1 and HPS4). Interacts with CLN5 (By similarity). Interacts with APPL2 (PubMed:25568335). Interacts with F8A1/F8A2/F8A3 (By similarity). Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A onto early endosomes (By similarity). Interacts with ATP9A (By similarity).|||Melanosome|||Membrane|||Phosphorylation of Ser-84 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including RAB GDP dissociation inhibitors GDI1 and GDI2.|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP.|||Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Active GTP-bound form is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes. Contributes to the regulation of filopodia extension. Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (By similarity). Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3 (PubMed:18425118).|||cytosol|||phagosome membrane|||ruffle http://togogenome.org/gene/10090:Tfe3 ^@ http://purl.uniprot.org/uniprot/A2AEW0|||http://purl.uniprot.org/uniprot/A2AEW1|||http://purl.uniprot.org/uniprot/Q3U1L5|||http://purl.uniprot.org/uniprot/Q64092 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MiT/TFE family.|||Homodimer and heterodimer; with TFEB or MITF (By similarity). Interacts with RRAGC/RagC GDP-bound and RRAGD/RagD GDP-bound; promoting its recruitment to lysosomal membrane in the presence of nutrients (PubMed:30595499). Interacts with TSC22D1; the interaction is enhanced in the presence of TGF-beta (PubMed:20713358).|||Induced by TGF-beta.|||Lysosome membrane|||Nucleus|||Phosphorylation ar Ser-47 and Ser-320 by MTOR via non-canonical mTORC1 pathway regulates its stability and subcellular location, respectively (PubMed:27913603). When nutrients are present, phosphorylation by MTOR at Ser-47 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (By similarity). When nutrients are present, phosphorylation by MTOR at Ser-320 also promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:27913603). Phosphorylation at Ser-47 plays a more critical role than phosphorylation at Ser-320 for TFE3 inactivation (By similarity). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and transcription factor activity (PubMed:27913603).|||Sumoylated; does not affect dimerization with MITF.|||Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:16936731, PubMed:29146937). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFEB or MITF (PubMed:16936731). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFE3 phosphorylation by MTOR promotes its inactivation (PubMed:27913603). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in transcription factor activity (PubMed:27913603). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (By similarity). Maintains the pluripotent state of embryonic stem cells by promoting the expression of genes such as ESRRB; mTOR-dependent TFE3 cytosolic retention and inactivation promotes exit from pluripotency (PubMed:23582324). Required to maintain the naive pluripotent state of hematopoietic stem cell; mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of hematopoietic stem cell from pluripotency (By similarity). TFE3 activity is also involved in the inhibition of neuronal progenitor differentiation (PubMed:30595499). Acts as a positive regulator of browning of adipose tissue by promoting expression of target genes; mTOR-dependent phosphorylation promotes cytoplasmic retention of TFE3 and inhibits browning of adipose tissue (PubMed:27913603). In association with TFEB, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (PubMed:16936731). Specifically recognizes the MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer (By similarity). It also binds very well to a USF/MLTF site (By similarity). Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TSC22D1 at E-boxes in the gene proximal promoter (PubMed:20713358). May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937).|||Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-47 by MTOR, leading to its degradation by the proteasome.|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Pcdha11 ^@ http://purl.uniprot.org/uniprot/Q91Y19 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Khdc4 ^@ http://purl.uniprot.org/uniprot/Q3TCX3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KHDC4 family.|||Cytoplasm|||Interacts with PRPF19. Isoform 2: Interacts with U2AF65.|||Nucleus|||RNA-binding protein involved in pre-mRNA splicing. Interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. Involved in regulating splice site selection. Binds preferentially RNA with A/C rich sequences and poly-C stretches.|||The C-terminal part is necessary for the interaction with the PRP19C/Prp19 complex/NTC/Nineteen complex.|||The KH domains mediate RNA-binding. http://togogenome.org/gene/10090:Tulp3 ^@ http://purl.uniprot.org/uniprot/O88413 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the IFT complex A (IFT-A) (By similarity). Interacts with SIRT1 (By similarity).|||Belongs to the TUB family.|||Cell membrane|||Cytoplasm|||Failure of neural tube closure and death by embryonic day 14.5. Failure of cranial neural tube closure coincident with increased neuroepithelial apoptosis specifically in the hindbrain and the caudal neural tube. In addition, the number of tubulin beta-3 positive cells is significantly decreased in the embryonic hindbrain. Morphological defects in the embryonic craniofacial regions, the spinal neural tube and the limbs.|||Negative regulator of the Shh signaling transduction pathway: recruited to primary cilia via association with the IFT complex A (IFT-A) and is required for recruitment of G protein-coupled receptor GPR161 to cilia, a promoter of PKA-dependent basal repression machinery in Shh signaling. Binds to phosphorylated inositide (phosphoinositide) lipids. Both IFT-A- and phosphoinositide-binding properties are required to regulate ciliary G protein-coupled receptor trafficking. During adipogenesis, regulates ciliary trafficking of FFAR4 in preadipocytes.|||Nucleus|||Secreted|||Ubiquitously expressed during development.|||Widely expressed including eyes and adipose depots.|||cilium http://togogenome.org/gene/10090:Scn1a ^@ http://purl.uniprot.org/uniprot/A2APX8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.1/SCN1A subfamily.|||Cell membrane|||Homozygous mice display severe seizures and premature death on postnatal day 15 (PubMed:16921370). Mice show severe motor deficits, including irregularity of stride length during locomotion, impaired motor reflexes in grasping and mild tremor in limbs when immobile, consistent with cerebellar dysfunction (PubMed:16921370). Heterozygous mice exhibit autistic-like behavior, characterized by hyperactivity, stereotyped behaviors, social interaction deficits and impaired context-dependent spatial memory (PubMed:22914087). Defects are caused by caused by impaired GABAergic neurotransmission (PubMed:22914087). Conditional knockout in forebrain GABAergic neurons leads to premature death caused by generalized tonic-clonic seizures in heterozygous mice (PubMed:22908258).|||Inactivation of this channel is specifically inhibited by the spider toxins Hm1a and Hm1b (H.maculata, AC P60992 and AC P0DOC5) in somatosensory neurons to elicit acute pain and mechanical allodynia (PubMed:27281198).|||Mediates the voltage-dependent sodium ion permeability of excitable membranes (PubMed:16921370, PubMed:17928448, PubMed:27281198). Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons (PubMed:16921370, PubMed:22914087). Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli (PubMed:27281198).|||Phosphorylation at Ser-1516 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.|||Present in cerebellar Purkinje neurons (at protein level) (PubMed:17928448). Expressed by myelinated, non-C-fiber neurons in sensory ganglia (PubMed:27281198).|||The S3b-S4 and S1-S2 loops of repeat IV are targeted by H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b depends on S1-S2 loops of repeat IV (PubMed:27281198).|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.|||The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B). Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by disulfide bonds. Interacts with FGF13. Interacts with the conotoxin GVIIJ. http://togogenome.org/gene/10090:Slc39a8 ^@ http://purl.uniprot.org/uniprot/Q91W10 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:29337306). Transports an electroneutral complex composed of a divalent metal cation and two bicarbonate anions or alternatively a bicarbonate and a selenite anion (PubMed:16638970, PubMed:18037372, PubMed:22563477, PubMed:27166256). Thereby, it also contributes to the cellular uptake of selenium, an essential trace metal and micronutrient (PubMed:27166256). Also imports cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:15722412, PubMed:16638970, PubMed:17108009, PubMed:18037372, PubMed:24529376). May also transport iron and cobalt through membranes (PubMed:16638970, PubMed:22898811, PubMed:24529376). Through zinc import, indirectly regulates the metal-dependent transcription factor MTF1 and the expression of some metalloproteases involved in cartilage catabolism and also probably heart development (PubMed:24529376, PubMed:29337306). Also indirectly regulates the expression of proteins involved in cell morphology and cytoskeleton organization (PubMed:29927450). Indirectly controls innate immune function and inflammatory response by regulating zinc cellular uptake which in turn modulates the expression of genes specific of these processes (PubMed:23403290). Protects, for instance, cells from injury and death at the onset of inflammation (By similarity). By regulating zinc influx into monocytes also directly modulates their adhesion to endothelial cells and arteries (PubMed:30015240). Reclaims manganese from the bile at the apical membrane of hepatocytes, thereby regulating the activity of the manganese-dependent enzymes through the systemic levels of the nutrient (PubMed:28481222). Also participates in manganese reabsorption in the proximal tubule of the kidney (By similarity). By mediating the extracellular uptake of manganese by cells of the blood-brain barrier, may also play a role in the transport of the micronutrient to the brain. With manganese cellular uptake also participates in mitochondrial proper function (By similarity). Finally, also probably functions intracellularly, translocating zinc from lysosome to cytosol to indirectly enhance the expression of specific genes during TCR-mediated T cell activation (By similarity).|||Expressed in the developing heart by cardiac endothelial cells with a peak of expression at 12.5 dpc and a decline to low levels in adult heart.|||Homodimer.|||Lysosome membrane|||N-glycosylated (PubMed:16638970). N-glycosylation is not required for proper iron and zinc transport (By similarity).|||The decreased expression of the channel in testis vascular endothelial cells confers the resistance to cadmium-induced testicular damage trait to some mice strains.|||The homozygous knockout of Slc39a8 is embryonic lethal by 16.5 dpc. Hearts exhibit hypertrabeculation and non-compaction phenotypes including excessive trabeculae and thin compact myocardium. These phenotypes are evident at 12.5 dpc and prominent at 14.5 dpc, and embryos that survive until 16.5 dpc display an even stronger phenotype. Ventricular septal defects are also observed. Some 14.5 dpc embryos exhibit body edema, suggesting that cardiac muscle function is compromised. Hearts display increased cardiomyocyte proliferation (PubMed:29337306). This is associated with decreased expression of metalloproteases and impaired degradation of the extracellular matrix leading to its aberrant accumulation in heart (PubMed:29337306). In mice homozygous for an hypomorphic allele of the gene, resulting in significant decreased expression of the protein, hematopoiesis and the development of multiple organs are affected from very early embryogenesis (PubMed:22563477). Conditional knockout of the gene at the level of the whole organism decreases manganese levels in tissues but has no effect on zinc and iron (PubMed:28481222). Conditional liver-specific knockout of the gene results in decreased systemic tissue manganese levels coupled to increased manganese in bile but has no effect on zinc or iron levels (PubMed:28481222).|||Ubiquitously expressed.|||Up-regulated in monocytes upon adhesion and recruitment to arteries (PubMed:30015240). Up-regulated by the pro-inflammatory cytokine interleukin-1 beta/IL1B (PubMed:24529376). http://togogenome.org/gene/10090:Foxf2 ^@ http://purl.uniprot.org/uniprot/O54743 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with the transcription factors TBP and TFIIB.|||Nucleus|||Probable transcription activator for a number of lung-specific genes (PubMed:9676429). Mediates up-regulation of the E3 ligase IRF2BPL and drives ubiquitination and degradation of CTNNB1 (By similarity).|||Two activation domains, AD1 and AD2, C-terminal of (and distinct from) the forkhead domains are necessary for transcriptional activation.|||Uniquely expressed in the bronchiolar epithelium and in type II pneumocytes. http://togogenome.org/gene/10090:Pdlim7 ^@ http://purl.uniprot.org/uniprot/Q3TJD7 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Anchored to cell periphery via its N-terminal PDZ domain.|||At 13.5 dpc expressed in epaxial, intercostal, and other skeletal muscles at the brachial level, including the latissimus dorsi muscle. Expressed in the intrinsic and extrinsic muscle mass of the tongue. At 15 dpc expressed in mesenchymal tissue surrounding the cartilaginous anlage of immature bones, and in the future joint spaces. As endochondral ossification progresses, and the hypertrophic cartilage zone is replaced by mineralized bone, expression appears in the mineralizing portion of the bone. Expressed in mesoderm derived bones of the skull base and neural crest-derived endochondral bones such as the proximal mandible.|||Cytoplasm|||May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Involved in both of the two fundamental mechanisms of bone formation, direct bone formation (e.g. embryonic flat bones mandible and cranium), and endochondral bone formation (e.g. embryonic long bone development). Plays a role during fracture repair. Involved in BMP6 signaling pathway (By similarity).|||Specifically binds via its LIM zinc-binding 3 domain (LIM 3) domain to endocytic codes of INSR, but not with those of IGF1R, LDLR, TFRC, or EGFR. Interacts with various PKC isoforms through the LIM zinc-binding domains. Binds to RET in a phosphorylation-independent manner via its LIM zinc-binding domain 2 (LIM 2). Probably part of a complex with SHC and the RET dimer. Interacts with TPM2, TBX4 and TBX5 (By similarity).|||The LIM zinc-binding 2 domain (LIM 2) interacts with TBX4.|||The LIM zinc-binding 3 domain (LIM 3) provides the structural basis for recognition of tyrosine-containing tight turn structures. This domain is necessary and sufficient for interaction with TBX5 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Apobec2 ^@ http://purl.uniprot.org/uniprot/Q9WV35 ^@ Cofactor|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the cytidine and deoxycytidylate deaminase family.|||Binds 1 Zn(2+) ion per subunit.|||Expressed exclusively in heart and skeletal muscle.|||Homotetramer.|||Probable C to U editing enzyme whose physiological substrate is not yet known. Does not display detectable apoB mRNA editing. Has a low intrinsic cytidine deaminase activity. May play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation. http://togogenome.org/gene/10090:Cript ^@ http://purl.uniprot.org/uniprot/O70333 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). Involved in the cytoskeletal anchoring of DLG4 in excitatory synapses (By similarity).|||Belongs to the CRIPT family.|||Component of the minor spliceosome. Within this complex, interacts with RNF113A, as well as with SF3B1/SF3b155, SF3B2/SF3b145 and PHF5A/SF3b14b (By similarity). Interacts with TUBB1. Interacts strongly with the PDZ3 domain of members of the DLG4 family. Associates with microtubules (By similarity). Interacts with DLG4.|||Cytoplasm|||Synapse|||dendritic spine http://togogenome.org/gene/10090:Axdnd1 ^@ http://purl.uniprot.org/uniprot/Q3UZ57 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping and sperm flagellum assembly.|||First detected in middle pachytene spermatocytes at stage VII to the early spermatids. Detected in spermatids until step 8, weakened in step 9 and almost disappeared in step 10.|||Highly expressed in testes (PubMed:34759295). Mainly expressed in the round and late spermatids (PubMed:34759295). Expression is detected also in the brain, lungs, spleen, and intestine (PubMed:35386379).|||Mutant mice are viable and show no abnormalities. However, Axdnd1-deficient males are sterile with reduced testis size caused by increased germ cell apoptosis (PubMed:35386379, PubMed:34759295). Testicular late spermatids are deformed with abnormal manchette structure, thereby causing male infertility (PubMed:34759295, PubMed:35386379). http://togogenome.org/gene/10090:Cd63 ^@ http://purl.uniprot.org/uniprot/P41731|||http://purl.uniprot.org/uniprot/Q549D0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Cell surface|||Endosome membrane|||Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli.|||Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1. Interacts with CD9. Identified in a complex with CD9 and ITGB3. Interacts with PMEL. Interacts with KDR/VEGFR2; identified in a complex with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1 complexes (By similarity). Interacts with SYT7 (PubMed:21041449).|||Late endosome membrane|||Lysosome membrane|||Melanosome|||Membrane|||No visible phenotype. Mutant mice are viable and fertile, but display impaired water homeostasis, with increased urinary flow, increased water intake, reduced urine osmolality and increased fecal water content. Mice display inclusions in the principal cells in the renal collecting duct (PubMed:19075008). Mutant mice display variable graying of their coat color and a dramatic reduction in the number of melanosomes in the retinal pigment epithelium (PubMed:21962903). According to PubMed:21803846, mutant mice display a defect in the Selp-dependent attachment of leukocytes to endothelial cells. According to PubMed:23945142, mast cells from mutant mice show decreased degranulation and decreased release of TNF in response to Ms4a2/FceRI stimulation, but no difference in mast cell degranulation in response to other stimuli and no change in the release of IL6 and leukotriene C4.|||Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro) (By similarity).|||Ubiquitous. Strongly expressed in kidney. Detected in spleen, bone marrow, peripheral blood mononuclear cells and macrophages.|||extracellular exosome|||multivesicular body http://togogenome.org/gene/10090:Zglp1 ^@ http://purl.uniprot.org/uniprot/Q1WG82 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ During female embryogenesis, specifically and transiently expressed in germ cells expressing Ddx4: expression starts at 12.0 dpc and decreases after 14.5 dpc, a key period for the sex determination of germ cells (PubMed:21123517, PubMed:32054698). Not expressed in somatic cells or males during embryogenesis (PubMed:32054698).|||Mice are viable and normal; however, both males and females are completely infertile (PubMed:16982049, PubMed:32054698). In females, Zglp1 absence leads to a severe block in germ cell development as early as 17.5 dpc (PubMed:16982049). Ovaries at postnatal day (P) 8 and 6 weeks are highly atrophic with no ovarian follicles (PubMed:32054698). Ovaries as early as 17.5 dpc contain a drastically reduced number of cells expressing Ddx4 (PubMed:32054698). In males, Zglp1 absence leads to defective sperm development with a marked reduction in mature spermatids observed as early as postnatal week 1 (PubMed:16982049). Male germ cells develop normally until P7 (PubMed:32054698). Subsequently, they display severe impairment in the first wave of spermatogenesis: unlike in females, germ cells entered into meiotic prophase, but fail to progress beyond the zygotene stage, resulting in a large fraction of abnormal pachytene cells both at P15 and P20 (PubMed:32054698).|||Nucleus|||Specifically expressed in adult testis and ovary (PubMed:16982049). Expressed at high levels in the somatic cells of the developing gonads, including Leydig cells in the testes and granulosa cells in the ovaries (PubMed:16982049).|||Transcriptional regulator that plays a key role in germ cell development (PubMed:16982049, PubMed:21123517, PubMed:32054698). Determines the oogenic fate by activating key genes for the oogenic program and meiotic prophase entry (PubMed:32054698). Acts downstream of bone morphogenetic protein (BMP) by regulating expression of genes required for the oogenic programs, which are repressed by Polycomb activities in sexually uncommitted germ cells (PubMed:32054698). Regulates expression of STRA8, a central downstream effector for the meiotic program (PubMed:32054698). Acts independently of retinoic acid (RA) (PubMed:32054698). In males, not required for germ-cell sex determination, but required to allow the spermatogonia to efficiently accomplish the meiotic prophase (PubMed:32054698).|||Up-regulated in response to bone morphogenetic proteins (BMPs) signaling. http://togogenome.org/gene/10090:Klra5 ^@ http://purl.uniprot.org/uniprot/Q548A2|||http://purl.uniprot.org/uniprot/Q60652 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer; disulfide-linked.|||Membrane|||Mostly expressed in NK cells, but also observed on NK T and memory T-cells.|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Ptpre ^@ http://purl.uniprot.org/uniprot/A0A1B0GRH2|||http://purl.uniprot.org/uniprot/A0A1B0GRT6|||http://purl.uniprot.org/uniprot/P49446|||http://purl.uniprot.org/uniprot/Q3V1H5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A catalytically active cytoplasmic form (p65) is produced by proteolytic cleavage of either isoform 1, isoform 2 or isoform 3.|||Acts as a negative regulator of insulin receptor (IR) signaling and is involved in insulin-induced glucose metabolism mainly through direct dephosphorylation and inactivation of IR in hepatocytes and liver (By similarity). Plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function.|||Acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake.|||Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.|||Cell membrane|||Cytoplasm|||Glycosylated.|||Induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and its induction is dependent upon PKC activity.|||Inhibited by alendronate (ALN), orthovanadate, and phenylarsine oxide (PAO).|||Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+).|||Isoform 2 is expressed in the spleen and thymus (at protein level). Detected in fibroblasts, myeloid cells, macrophages, and T-cells but not in B-cell lines. Isoform 1 and isoform 2 are expressed predominantly in the brain, testes, and lungs, with lower levels present in lymph nodes, thymus, spleen, heart and mammary glands. Isoform 1 is expressed in osteoclasts and not in osteoblasts and its expression is related to osteoclast differentiation. It is also expressed in the erythrocytes. Isoform 2 is strongly expressed in skeletal muscle and L6 skeletal muscle cell line.|||Membrane|||Mice show greater insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1) in the skeletal muscle. Antigen- and IgE-mediated passive systemic anaphylactic reactions are enhanced. Erythrocytes exhibit abnormal morphology, increased Ca(2+)-activated-K(+) channel activity and marked perturbation of the erythrocyte membrane tyrosine phosphoproteome.|||Monomer (By similarity). Isoform 2: Homodimer. Can form oligomers. Dimerization is increased by oxidative stress and decreased by EGFR. Isoform 2 interacts with GRB2 (By similarity).|||Phosphorylated on tyrosine residues by tyrosine kinase Neu.|||Produced by alternative initiation at Met-85 of isoform 1.|||Produced by alternative promoter usage.|||The tyrosine-protein phosphatase 2 domain (D2) mediates dimerization. The extreme N- and C- termini of the D2 domain act to inhibit dimerization and removal of these sequences increases dimerization and inhibits enzyme activity. http://togogenome.org/gene/10090:Ccdc88b ^@ http://purl.uniprot.org/uniprot/Q4QRL3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in immune cells, including both CD4(+) and CD8(+) T-cells and in myeloid cells (at protein level) (PubMed:25403443). Expressed in endothelium (at protein level) (PubMed:21289099). Expressed specifically in spleen, bone marrow, lymph nodes and thymus (PubMed:25403443). Expressed in liver and heart (PubMed:21289099).|||Acts as a positive regulator of T-cell maturation and inflammatory function. Required for several functions of T-cells in both the CD4(+) and the CD8(+) compartments and this includes expression of cell surface markers of activation, proliferation, and cytokine production in response to specific or non-specific stimulation and during the course of infection with the mouse malaria parasite Plasmodium berghei (PubMed:25403443). Enhances NK cell cytotoxicity by positively regulating polarization of microtubule-organizing center (MTOC) to cytotoxic synapse, lytic granule transport along microtubules, and dynein-mediated clustering to MTOC (By similarity). Interacts with HSPA5 and stabilizes the interaction between HSPA5 and ERN1, leading to suppression of ERN1-induced JNK activation and endoplasmic reticulum stress-induced apoptosis (PubMed:21289099).|||Belongs to the CCDC88 family.|||Cytoplasm|||Endoplasmic reticulum|||Golgi apparatus|||Homodimer (By similarity). Interacts with DOCK8 (By similarity). Interacts (via C-terminus) with intact microtubules (By similarity). Interacts with dynein-dynactin motor complex (By similarity). Interacts (via C-terminus) with HSPA5 (PubMed:21289099).|||Membrane|||Mice show defects in T-cell functions including impaired maturation, significantly reduced activation, reduced cell division as well as impaired cytokine production in response to specific or non-specific stimulation and during the course of infection with the mouse malaria parasite Plasmodium berghei.|||microtubule organizing center http://togogenome.org/gene/10090:Arrdc5 ^@ http://purl.uniprot.org/uniprot/Q497K5 ^@ Similarity ^@ Belongs to the arrestin family. http://togogenome.org/gene/10090:Slc25a29 ^@ http://purl.uniprot.org/uniprot/Q8BL03 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||By partial hepactectomy and fasting.|||Mitochondrial transporter of arginine, lysine, homoarginine, methylarginine (By similarity). Transports with a much lesser extent, ornithine and histidine (PubMed:19287344). Does not transport carnitine nor acylcarnitines. Functions by both counter-exchange and uniport mechanisms. Plays a physiolocical role in the import of basic amino acids into mitochondria for mitochondrial protein synthesis and amino acid degradation (By similarity).|||Mitochondrion inner membrane|||Was initially proposed to transport palmitoylcarnitine, based on complementation experiments in yeast mutants lacking CRC1 and CIT2 and release of radiolabeled carnitine from mitochondria incubated with radiolabeled palmitoylcarnithine (PubMed:12882971). Later experiments done primarily with human indicate the protein functions instead as transporter of basic amino acids (By similarity).|||Widely expressed, with highest levels in the brain, including cortex, cerebellum, hippocampus and hypothalamus, and moderate levels in liver, kidney, heart and testis. http://togogenome.org/gene/10090:Vmn2r49 ^@ http://purl.uniprot.org/uniprot/D3Z6L3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Prpf4b ^@ http://purl.uniprot.org/uniprot/Q61136 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.|||Has a role in pre-mRNA splicing. Phosphorylates SF2/ASF.|||Identified in the spliceosome C complex (By similarity). Interacts with Clk1 C-terminus.|||Nucleus|||Phosphorylated by Clk1. http://togogenome.org/gene/10090:Ssr2 ^@ http://purl.uniprot.org/uniprot/Q9CPW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAP-beta family.|||Endoplasmic reticulum membrane|||Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma. Interacts with STING1 (By similarity).|||TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. http://togogenome.org/gene/10090:Phf7 ^@ http://purl.uniprot.org/uniprot/Q9DAG9 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression levels increase during the first 4 weeks after birth and remain constant during the following 3 weeks.|||Highly expressed in Sertoli cells in testis.|||May play a role in spermatogenesis.|||Nucleus http://togogenome.org/gene/10090:Hapln4 ^@ http://purl.uniprot.org/uniprot/Q80WM4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HAPLN family.|||Essential for the proper localization of brevican (BCAN), mainly as a perineuronal nets (PNNs)-type deposition in the brainstem and cerebellum thereby playing a key role in the formation and structural organization of PNNs (PubMed:22121037). Contributes to the formation and transmission of inhibitory GABAergic synapses between Purkinje cells and deep cerebellar nuclei neurons (PubMed:30125937).|||Expressed predominantly in brain where it is found mainly throughout the midbrain and hindbrain in a perineuronal net pattern.|||Expression begins at embryonic day 20 and increases thereafter. Expression continues into adulthood.|||In deep cerebellar nuclei (DCN) neurons of knockout mice, inhibitory synaptic strengths are reduced as compared to those in wild-type mice, whereas the properties of excitatory synapses are unaffected (PubMed:30125937). A reduction in GABAergic pre-synaptic terminals of Purkinje cells are seen in the DCN neurons (PubMed:30125937). Mice show significantly attenuated perineuronal nets formation in the DCN, a marked decrease of brevican (BCAN) in the brainstem and cerebellum and a reduction in synapse number in the DCN neurons (PubMed:22121037).|||extracellular matrix http://togogenome.org/gene/10090:Rad1 ^@ http://purl.uniprot.org/uniprot/Q9QWZ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rad1 family.|||Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. Isoform 1 possesses 3'->5' double stranded DNA exonuclease activity (By similarity).|||Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. RAD1 interacts with POLB, FEN1, HUS1, HUS1B, RAD9A and RAD9B. Interacts with DNAJC7 (By similarity).|||Expressed in testis, uterus, bladder, spleen, ovaries, lung, brain and muscle (at protein level). Expressed in brain, testis, kidney, heart, liver and lung.|||Nucleus http://togogenome.org/gene/10090:Plscr4 ^@ http://purl.uniprot.org/uniprot/P58196|||http://purl.uniprot.org/uniprot/Q8BV91 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phospholipid scramblase family.|||Interacts with PDCD6.|||May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane.|||May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system.|||Membrane|||The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity. http://togogenome.org/gene/10090:Limk2 ^@ http://purl.uniprot.org/uniprot/O54785 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Binds ROCK1 and MARF1 (By similarity). Interacts with NISCH (PubMed:18332102).|||Cytoplasm|||Nucleus|||Phosphorylated on serine and/or threonine residues by ROCK1.|||Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP. Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro. Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (By similarity).|||Specifically expressed in the testes.|||centrosome|||perinuclear region|||spindle http://togogenome.org/gene/10090:Or4c11b ^@ http://purl.uniprot.org/uniprot/Q8VGF5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pafah1b3 ^@ http://purl.uniprot.org/uniprot/Q61205 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha1 catalytic subunit of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and modulates the action of PAF. The activity and substrate specificity of PAF-AH (I) are affected by its subunit composition. Both alpha1/alpha1 homodimer (PAFAH1B3/PAFAH1B3 homodimer) and alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B2 heterodimer) hydrolyze 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA) more efficiently than PAF, but they have little hydrolytic activity towards 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE). Plays an important role during the development of brain.|||Belongs to the 'GDSL' lipolytic enzyme family. Platelet-activating factor acetylhydrolase IB beta/gamma subunits subfamily.|||Beta subunit (PAFAH1B1) inhibits the acetylhydrolase activity of the alpha1/alpha1 catalytic homodimer.|||Cytoplasm|||Expressed already by the time of neurulation. By 10.5 dpc, expression is abundant in the developing central and peripheral nervous systems. Major sites include the neuroepithelium of the fore-, mid-, and hindbrain, the spinal cord, the dorsal root, and cranial ganglia. In adult brain, expression is greatly diminished.|||Forms a catalytic dimer which is either homodimer (alpha1/alpha1 homodimer) or heterodimer with PAFAH1B2 (alpha1/alpha2 heterodimer). Component of the cytosolic (PAF-AH (I)) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity (By similarity). Interacts with VLDLR; this interaction may modulate the Reelin pathway (PubMed:17330141).|||Knockout mice which are homozygous for the PAFAH1B2 gene appear developmentally normal, and are born at the expected Mendelian rate. Mice have normal fertility and normal spermatogenesis. Double mutant female mice which are homozygous for PAFAH1B2 and PAFAH1B3 are grossly normal and fertile, whereas double-mutant males are infertile. Double mutan mice manifest an earlier disturbance of spermatogenesis with an onset at preleptotene or leptotene stages of meiosis.|||Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity). http://togogenome.org/gene/10090:Gprin1 ^@ http://purl.uniprot.org/uniprot/Q3UNH4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed specifically in brain (at protein level).|||Interacts with activated forms of GNAI1, GNAO1 and GNAZ.|||May be involved in neurite outgrowth.|||Palmitoylation on Cys-923 and/or Cys-924 is required for membrane targeting.|||growth cone http://togogenome.org/gene/10090:Tbx2 ^@ http://purl.uniprot.org/uniprot/Q3UET7|||http://purl.uniprot.org/uniprot/Q60707 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA as a monomer (By similarity). Interacts with CHD4, HDAC1 and HDAC2, perhaps as components of a NuRD-like complex (PubMed:33731112). Interacts with CBX3, HMGB2 and PBX1 (PubMed:33731112). Interacts with PML (By similarity).|||Expressed in the otic placode at 8.5 dpc (at protein level) (PubMed:33795231). Between 10.5-12.0 dpc, expressed in various regions of the developing ear, including the cochlear duct, endolymphatic duct and the vestibule, but not in the region which gives rise to the posterior and anterior semicircular canals (at protein level) (PubMed:33795231). Expressed at 8.5 dpc in the cardiac crescent, the atrium and the inflow tract (IFT) (PubMed:15459098). Expressed at 9.5 dpc in the otic and optic vesicles, facial region, septum transversum, bilateral nephrogenic mesodermal cords, ventral body wall mesoderm caudal to the forelimbs, pharyngeal arch mesenchyme that contains neural crest cells, including those migrating into the outflow tract (OFT), septum OFT, inner curvature, atrioventricular canal (AVC) and IFT of the heart (PubMed:7920656, PubMed:8853987, PubMed:15459098, PubMed:33795231). Expressed in a continuous stripe of mesenchyme in the ventro-lateral body wall between the fore and hind limb buds at day 10.5-11.5 dpc (PubMed:16222716). At 12.5 dpc, expressed in the trigeminal ganglia, facial regions, retina and limb bud mesenchyme (PubMed:8853987). In later stages, found in ear pinnae, the milk line, lung mesenchyme, body wall, genital ridge and developing nervous system (PubMed:8853987, PubMed:33731112). Expressed in proliferating retinal pigment epithelium (RPE) cells at 14.5 dpc, and continues after birth, but diminishes by postnatal day 90 (PubMed:28910203). Expressed in melanocytes of postnatal day 3 hair follicles (PubMed:26486273).|||In adults, highest levels in lung. Also found in heart, kidney, and ovary.|||Knockouts do not survive beyond embryonic 14.5 dpc (PubMed:15459098). Abnormal atrioventricular morphology at 9.5-10.5 dpc and outflow tract (OFT) septation defects in those surviving to 12.5 dpc (PubMed:15459098). Hindlimb digit duplication at 14.5 dpc (PubMed:15459098). Increased expression of CDKN1A, FRZB, IL33, SHISA3, and CCN4/WISP1 in lung mesenchyme between 12.5-14.5 dpc (PubMed:33731112). Conditional knockdown targeted mainly to lung mesenchyme causes lung hypoplasia at 18.5 dpc (PubMed:27720610). Conditional knockdown targeted mainly to the otic epithelium disrupts inner ear morphogenesis, which is exacerbated by simultaneous conditional knockdown of TBX3 (PubMed:33795231). Simultaneous conditional knockdown of TBX2 and TBX3 targeted mainly to lung mesenchyme causes severe bleeding from 10.5 dpc and embryos die shortly thereafter, perhaps as a result of knockdown in the developing heart (PubMed:27720610).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Phosphorylated (PubMed:18025091). May be phosphorylated by p38 MAPK in response to UV irradiation stress (PubMed:18025091).|||Repression domain 1 (RD1) is involved in transcriptional repression (By similarity). RD1 is necessary for its interaction with PML (By similarity).|||Transcription factor which acts as a transcriptional repressor (PubMed:22186728, PubMed:11867218, PubMed:18025091, PubMed:12023302). May also function as a transcriptional activator (PubMed:26486273, PubMed:22186728, PubMed:11867218). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (PubMed:9710594, PubMed:26971330, PubMed:12023302, PubMed:33731112, PubMed:27720610). Required for cardiac atrioventricular canal formation (PubMed:15459098). May cooperate with NKX2.5 to negatively modulate expression of NPPA/ANF in the atrioventricular canal (PubMed:12023302). May play a role as a positive regulator of TGFB2 expression, perhaps acting in concert with GATA4 in the developing outflow tract myocardium (PubMed:22186728). Plays a role in limb pattern formation (PubMed:15459098). Acts as a transcriptional repressor of ADAM10 gene expression, perhaps in concert with histone deacetylase HDAC1 as cofactor (PubMed:30599067). Involved in branching morphogenesis in both developing lungs and adult mammary glands, via negative modulation of target genes; acting redundantly with TBX3 (PubMed:27720610, PubMed:16222716). Required, together with TBX3, to maintain cell proliferation in the embryonic lung mesenchyme; perhaps acting downstream of SHH, BMP and TGFbeta signaling (PubMed:27720610). Involved in modulating early inner ear development, acting independently of, and also redundantly with TBX3, in different subregions of the developing ear (PubMed:33795231). Acts as a negative regulator of PML function in cellular senescence (By similarity). Acts as a negative regulator of expression of CDKN1A/p21, IL33 and CCN4; repression of CDKN1A is enhanced in response to UV-induced stress, perhaps as a result of phosphorylation by p38 MAPK (PubMed:18025091, PubMed:33731112). Negatively modulates expression of CDKN2A/p19ARF and CDH1/E-cadherin (By similarity). Plays a role in induction of the epithelial-mesenchymal transition (EMT) (By similarity). Plays a role in melanocyte proliferation, perhaps via regulation of cyclin CCND1 (PubMed:26486273). Involved in melanogenesis, acting via negative modulation of expression of DHICA oxidase/TYRP1 and P protein/OCA2 (PubMed:26971330, PubMed:9710594). Involved in regulating retinal pigment epithelium (RPE) cell proliferation, perhaps via negatively modulating transcription of the transcription factor CEBPD (PubMed:28910203). http://togogenome.org/gene/10090:Pilrb1 ^@ http://purl.uniprot.org/uniprot/Q2YFS2 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with CD99. Probably associates with DAP12.|||Membrane|||Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRB is thought to act as a cellular signaling activating receptor that associates with ITAM-bearing adapter molecules on the cell surface. Seems to associate with DAP12 and is a receptor for CD99. May be involved in target cell recognition by natural killer cells and in activation of dendritic cells.|||Widely expressed with highest levels in spleen, liver and lung. Predominantly expressed by natural killer cells, macrophages, and granulocytes and dendritic cells (BM-DC). http://togogenome.org/gene/10090:Ldah ^@ http://purl.uniprot.org/uniprot/A0A0F6AIX5|||http://purl.uniprot.org/uniprot/A0A0F6AIX6|||http://purl.uniprot.org/uniprot/A0A1W2P7C8|||http://purl.uniprot.org/uniprot/Q8BVA5 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. LDAH family.|||Endoplasmic reticulum|||Expressed in liver, adrenal gland, prostate, spleen, kidney, brown and white adipose tissue, testis and to a lesser extent in brain (at protein level) (PubMed:27836991). Expressed in bone marrow-derived macrophages (at protein level) (PubMed:27836991). Expressed in heart (PubMed:27836991). Highly expressed in macrophage-rich areas in atherosclerotic lesions (PubMed:24357060).|||Lipid droplet|||Mice have no obvious defects (PubMed:27836991). Size of adipocytes is normal (PubMed:27836991). Lipid metabolism is normal (PubMed:27836991). Cholesterol ester turnover or hydrolysis in bone marrow macrophages, brown adipose tissue or liver is normal (PubMed:27836991). No defect in body composition, energy expenditure, locomotor activity, water or food intake, respiratory exchange ratio, oxygen consumption, carbon dioxide production or glucose homeostasis (PubMed:27836991).|||Probable serine lipid hydrolase associated with lipid droplets (PubMed:24357060). Appears to lack cholesterol esterase activity (PubMed:24357060, PubMed:27836991). Appears to lack triglyceride lipase activity (PubMed:23525007, PubMed:24357060, PubMed:27836991). Highly expressed in macrophage-rich areas in atherosclerotic lesions, suggesting that it could promote cholesterol ester turnover in macrophages (PubMed:24357060).|||The catalytic activity is unsure despite catalytic sites being conserved (PubMed:23525007, PubMed:27836991). One report shows that LDAH has low cholesterol esterase activity when overexpressed in RAW 264.7 macrophages (PubMed:24357060). However, in another study, LDAH lacks cholesterol esterase activity when overexpressed in Hela cells (PubMed:27836991). Lack lipolytic activity towards trioleoylglycerol, dioleoylglycerol or monooleoylglycerol when overexpressed in COS-7 cells or Hela cells (PubMed:23525007, PubMed:27836991). http://togogenome.org/gene/10090:Spink1 ^@ http://purl.uniprot.org/uniprot/P09036 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By androgens in adult male sex accessory glands. Expressed constitutively in pancreas.|||In the genital tract, expressed only in male accessory glands including seminal vesicle, coagulating gland and prostate.|||In the male reproductive tract, binds to sperm heads where it modulates sperm capacitance by inhibiting calcium uptake and nitrogen oxide (NO) production (PubMed:9828198, PubMed:14645103, PubMed:16083722, PubMed:22228629).|||In the seminal vesicle, not expressed during prepubertal stages; expression coincides with maturation.|||Lethal with no survival past two weeks of age. Animals are small and show severe, progressive degeneration of pancreatic tissue associated with autophagic cell death.|||Secreted|||Serine protease inhibitor which exhibits anti-trypsin activity (PubMed:3428272, PubMed:14645103, PubMed:22228629). In the pancreas, protects against trypsin-catalyzed premature activation of zymogens (PubMed:16083722). http://togogenome.org/gene/10090:Elp3 ^@ http://purl.uniprot.org/uniprot/Q9CZX0 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ELP3 family.|||Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||Catalytic tRNA acetyltransferase subunit of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (By similarity). In the elongator complex, acts as a tRNA uridine(34) acetyltransferase by mediating formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity). May also act as a protein lysine acetyltransferase by mediating acetylation of target proteins; such activity is however unclear in vivo and recent evidences suggest that ELP3 primarily acts as a tRNA acetyltransferase (By similarity). Involved in neurogenesis: regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (PubMed:19185337). Required for acetylation of GJA1 in the developing cerebral cortex (PubMed:28507509).|||Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6. ELP1, ELP2 and ELP3 form the elongator core complex. Interacts with alpha-tubulin.|||Cytoplasm|||Embryonic lethality by 12.5 dpc caused by severe growth retardation (PubMed:27476491, PubMed:29415125). Conditional deletion in adults is also lethal (PubMed:29415125).|||Nucleus|||The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification.|||The relevance of the protein lysine acetyltransferase activity is unclear (By similarity). The publication reporting acetylation of GJA1 does not provide direct evidence of lysine acetyltransferase activity of ELP3 (PubMed:28507509).|||Tyrosine-phosphorylated. Also serine/threonine-phosphorylated.|||Ubiquitously expressed in blastocysts and 10.5 dpc embryos (PubMed:27476491). Expression increases during embryonic stem cell maintenance differentiation (PubMed:27476491). http://togogenome.org/gene/10090:Omd ^@ http://purl.uniprot.org/uniprot/O35103 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.|||Binds the alpha(V)beta(3)-integrin.|||Bone specific.|||Glycosylated; contains keratan sulfate.|||May be implicated in biomineralization processes. Has a function in binding of osteoblasts via the alpha(V)beta(3)-integrin.|||extracellular matrix http://togogenome.org/gene/10090:Fam90a1a ^@ http://purl.uniprot.org/uniprot/A2A4E2 ^@ Similarity ^@ Belongs to the FAM90 family. http://togogenome.org/gene/10090:Otop3 ^@ http://purl.uniprot.org/uniprot/F8VQ32|||http://purl.uniprot.org/uniprot/Q80UF9|||http://purl.uniprot.org/uniprot/Q9D7E9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the otopetrin family.|||Cell membrane|||Expressed in epidermis, small intestine, stomach and retina.|||Membrane|||Proton-selective channel that specifically transports protons into cells. Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes. http://togogenome.org/gene/10090:Zfp422 ^@ http://purl.uniprot.org/uniprot/Q9ERU3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds DNA through the consensus sequence 5'-CAATG-3'. May be involved in transcriptional regulation and may play a role in tooth formation.|||Expressed predominantly in developing craniofacial bones and dental organs, and in molar tooth germs of postnatal animals. Also detected in embryonic heart, liver, thymus, kidney, brain, lung, muscle and calvaria. In the adult, highly expressed in lung, kidney, bone and incisors.|||In the embryo, expression is detected from day 7 with highest levels between days 11 and 15.|||Nucleus http://togogenome.org/gene/10090:Rabggtb ^@ http://purl.uniprot.org/uniprot/P53612|||http://purl.uniprot.org/uniprot/Q3TVF4 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the protein prenyltransferase subunit beta family.|||Binds 1 zinc ion per subunit.|||Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A.|||Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX.|||Heterotrimer composed of RABGGTA, RABGGTB and CHM; within this trimer, RABGGTA and RABGGTB form the catalytic component B, while CHM (component A) mediates peptide substrate binding (PubMed:21520375). The Rab GGTase dimer (RGGT) interacts with CHM (component A) prior to Rab protein binding; the association is stabilized by geranylgeranyl pyrophosphate (GGpp) (By similarity). The CHM:RGGT:Rab complex is destabilized by GGpp (By similarity). Interaction of RABGGTB with prenylated PTP4A2 precludes its association with RABGGTA and inhibits enzyme activity (By similarity). Interacts with CHODL (PubMed:18161010). Interacts with non-phosphorylated form of RAB8A; phosphorylation of RAB8A at 'Thr-72' disrupts this interaction (By similarity).|||Increased dramatically by cycloheximide (CHX) treatment within a short time (as early as 2 hours). Actinomycin D was used to determine the half-life, CHX treatment resulted in a dramatic increase of the half-life from 8 hours to greater than 12 hours.|||Specific expression was elevated in mid-gestation stages, particularly developing liver and spinal cord.|||The enzymatic reaction requires the aid of a Rab escort protein (also called component A), such as CHM.|||Ubiquitous. Detected in all the major organs in adult animals. http://togogenome.org/gene/10090:Angel2 ^@ http://purl.uniprot.org/uniprot/Q8K1C0 ^@ Similarity ^@ Belongs to the CCR4/nocturin family. http://togogenome.org/gene/10090:Klhl2 ^@ http://purl.uniprot.org/uniprot/Q8JZP3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell projection|||Component of the BCR(KLHL2) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL2 and RBX1 (PubMed:21549840). Binds actin. Interacts with KLHL12 (By similarity). Interacts (via N-terminus) with FYN (via SH3 domain) (By similarity).|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates the ubiquitination of target proteins, such as NPTXR, WNK1, WNK3 and WNK4, leading most often to their proteasomal degradation (PubMed:21549840). The BCR(KLHL2) complex catalyzes ubiquitination and degradation of NPTXR (PubMed:21549840). Responsible for degradative ubiquitination of the WNK kinases WNK1, WNK3 and WNK4 (By similarity). Plays a role in the reorganization of the actin cytoskeleton (By similarity). Promotes growth of cell projections in oligodendrocyte precursors (By similarity).|||cytoskeleton|||cytosol|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Vmn2r48 ^@ http://purl.uniprot.org/uniprot/E9Q5D8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mtmr7 ^@ http://purl.uniprot.org/uniprot/Q9Z2C9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Endomembrane system|||Heterodimer (via C-terminus) with MTMR9 (via coiled coil domain); the interaction enhances MTMR7 catalytic activity (PubMed:12890864). Does not homodimerize (PubMed:12890864). Interacts with RAB1B (in GDP-bound form) (PubMed:23188820).|||Highly expressed in brain (at protein level). Expressed at low levels in liver, kidney and testis.|||Interaction with MTMR9 increases phosphatase activity.|||Phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and inositol 1,3-bisphosphate (Ins(1,3)P2). http://togogenome.org/gene/10090:Grm7 ^@ http://purl.uniprot.org/uniprot/G5E8D5|||http://purl.uniprot.org/uniprot/Q68ED2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||G-protein coupled receptor activated by glutamate that regulates axon outgrowth through the MAPK-cAMP-PKA signaling pathway during neuronal development (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase that it inhibits (By similarity).|||Homodimer (By similarity). Interacts with PICK1.|||Membrane http://togogenome.org/gene/10090:Cactin ^@ http://purl.uniprot.org/uniprot/A1L013|||http://purl.uniprot.org/uniprot/Q9CS00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CACTIN family.|||Expressed in cortex, hippocampus, cerebellum, heart, lung, kidney, liver, spleen and thymus.|||Interacts (via N-terminal domain) with NFKBIL1; the interaction occurs in a pro-inflammatory-independent manner (By similarity). Does not interact with RELA NF-kappa-B subunit (By similarity). Identified in the spliceosome C complex (By similarity). Interacts with SF3B1 (By similarity). Interacts with SDE2 (By similarity). Interacts with SRRM2 (By similarity). Interacts with DHX8 (By similarity).|||Nucleus|||Plays a role in pre-mRNA splicing by facilitating excision of a subset of introns (By similarity). Required for the splicing of CDCA5/Sororin, a regulator of sister chromatid cohesion (By similarity). Involved in the regulation of innate immune response (By similarity). Acts as negative regulator of Toll-like receptor, interferon-regulatory factor (IRF) and canonical NF-kappa-B signaling pathways (By similarity). Contributes to the regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous pro-inflammatory stimuli (By similarity).|||cytosol http://togogenome.org/gene/10090:Sirt2 ^@ http://purl.uniprot.org/uniprot/Q8VDQ8 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by EP300; acetylation leads both to the decreased of SIRT2-mediated alpha-tubulin deacetylase activity and SIRT2-mediated down-regulation of TP53 transcriptional activity.|||Belongs to the sirtuin family. Class I subfamily.|||Binds 1 zinc ion per subunit.|||Cell projection|||Chromosome|||Cytoplasm|||Deacetylates alpha-tubulin.|||Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide. Inhibited by a macrocyclic peptide inhibitor S2iL5. Inhibited by EP300-induced acetylation (By similarity).|||Interacts with CDC20, FOXO3 and FZR1 (PubMed:17521387, PubMed:22014574). Associates with microtubule in primary cortical mature neurons (By similarity). Homotrimer. Interacts (via both phosphorylated, unphosphorylated, active or inactive forms) with HDAC6; the interaction is necessary for the complex to interact with alpha-tubulin, suggesting that these proteins belong to a large complex that deacetylates the cytoskeleton. Interacts with FOXO1; the interaction is disrupted upon serum-starvation or oxidative stress, leading to increased level of acetylated FOXO1 and induction of autophagy (PubMed:17681146, PubMed:19037106). Interacts with RELA; the interaction occurs in the cytoplasm and is increased in a TNF-alpha-dependent manner. Interacts with HOXA10; the interaction is direct. Interacts with YWHAB and YWHAG; the interactions occur in a AKT-dependent manner and increase SIRT2-dependent TP53 deacetylation. Interacts with MAPK1/ERK2 and MAPK3/ERK1; the interactions increase SIRT2 stability and deacetylation activity. Interacts (phosphorylated form) with KMT5A isoform 2; the interaction is direct, stimulates KMT5A-mediated methyltransferase activity on histone at 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner. Interacts with G6PD; the interaction is enhanced by H(2)O(2) treatment. Interacts with a G1/S-specific cyclin E-CDK2 complex. Interacts with AURKA, CDK5R1 (p35 form) and CDK5 and HIF1A. Interacts with the tRNA ligase SARS1; recruited to the VEGFA promoter via interaction with SARS1 (By similarity). Isoform 2 and isoform 4 associate with microtubules in primary cortical mature neurons. Interacts with BEX4; negatively regulates alpha-tubulin deacetylation by SIRT2 (By similarity).|||Isoform 1 is expressed in the cortex at 15.5 dpc. Isoform 2 is not detected in the cortex at 15.5 dpc (at protein level).|||Isoform 1 is weakly expressed in the cortex at postnatal(P) days P1, P3 and P7, and increases progressively between P17 and older adult cortex. Isoform 1 is also expressed in heart, liver and skeletal muscle, weakly expressed in the striatum and spinal cord. Isoform 2 is not expressed in the cortex at P1, P3 and P7, and increases strongly and progressively between P17 and older adult cortex. Isoform 2 is also expressed in the heart, liver, striatum and spinal cord. Isoform 4 is weakly expressed in older adult cortex and spinal cords. Expressed in the cortex. Expressed in postnatal sciatic nerves during myelination and during remyelination after nerve injury. Expressed in neurons, oligodendrocytes, Schwann cells, Purkinje cells and in astrocytes of white matter. Strongly expressed in preadipocytes compared with differentiated adipocytes. Expressed in cerebellar granule cells. Expressed in the inner ear: in the cochlea, expressed in types I and V fibrocytes in the spiral ligament (SL) and slightly in stria vascularis (SV); in the organ of Corti, expressed in some supporting cells; in the crista ampullaris, expressed in spiral ganglion cells; also expressed in the endolymphatic sac (ES) epithelial cells (at protein level). Expressed in the brain, spinal cord, optic nerve and hippocampus. Strongly expressed in 6-8 week-old ovulated meiosis II oocytes and weakly expressed in 45-58 week-old ovulated meiosis II oocytes. Expressed in the cochlea, vestibule and acoustic nerve of the inner ear.|||Midbody|||Myelin membrane|||NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:17521387, PubMed:17681146, PubMed:17574768, PubMed:19037106, PubMed:22014574, PubMed:21791548, PubMed:21841822, PubMed:24334550). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells (PubMed:17574768, PubMed:21791548). Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity (PubMed:17681146, PubMed:19037106). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed:17681146, PubMed:19037106). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:17681146, PubMed:19037106). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (PubMed:17521387, PubMed:21841822). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor (PubMed:22014574, PubMed:23468428). In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes (By similarity).|||Nucleus|||Perikaryon|||Phosphorylated at phosphoserine and phosphothreonine. Phosphorylated at Ser-368 by a mitotic kinase CDK1/cyclin B at the G2/M transition; phosphorylation regulates the delay in cell-cycle progression. Phosphorylated at Ser-368 by a mitotic kinase G1/S-specific cyclin E/Cdk2 complex; phosphorylation inactivates SIRT2-mediated alpha-tubulin deacetylation and thereby negatively regulates cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Phosphorylated by cyclin A/Cdk2 and p35-Cdk5 complexes and to a lesser extent by the cyclin D3/Cdk4 and cyclin B/Cdk1, in vitro. Dephosphorylated at Ser-368 by CDC14A and CDC14B around early anaphase (By similarity).|||Tissue-specific knockout of SIRT2 in Schwann cells of early postnatal mice leads to a transient delay in myelination, a reduction in the nerve conduction velocity and hyperacetylation of PARD3. The number of dividing Schwann cells in the developing nerve and alpha-tubulin acetylation are normal (PubMed:21949390). Mutant mice embryo grow normally and new born are healthy. Embryonic fibroblasts (MEFs) display reduced cell proliferation capacity, centrosome amplification and mitotic cell death. Nude mice inoculated with immortalized MEFs from mutant mice developed tumors. Adult mutant mice exhibit genomic instability and chromosomal aberrations, such as double-strand breaks (DSBs), with a gender-specific spectrum of tumorigenesis; females develop primarily mammary tumors and males develop tumors in several organs, including the liver, lung, pancreas, stomach, duodenum and prostate. Drastic increases of histone H4K16 acetylation and decreases of both histone methylation (H4K20me1) in metaphasic chromosomes and histone methylations (H4K20me2/3) in late M/early G1 but also throughout all phases of the cell cycle (PubMed:23468428).|||Ubiquitinated.|||Up-regulated in response to caloric restriction in white and brown adipose tissues. Up-regulated during cold exposure and down-regulated in higher ambient temperature in brown adipose tissue. Up-regulated after beta-adrenergic agonist (isoproterenol) treatment in white adipose tissue (at protein level). Up-regulated in response to caloric restriction in adipose tissue and kidney. Up-regulated in response to oxidative stress. Up-regulated during postnatal sciatic nerve myelination development and axonal regeneration. Down-regulated during preadipocyte differentiation. Down-regulated in Schwann dedifferentiated cells during Wallerian degeneration. Isoform 1 is up-regulated upon differentiation to a neuron-like phenotype.|||centriole|||centrosome|||cytoskeleton|||growth cone|||perinuclear region|||spindle http://togogenome.org/gene/10090:Rims1 ^@ http://purl.uniprot.org/uniprot/Q99NE5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds SNAP25, SYT1 and CACNA1B. Interaction with SYT1 is enhanced by calcium ions. Interaction with SNAP25 is weaker in the presence of calcium ions. Interacts with TSPOAP1 and RIMBP2; interacts with PPFIA3 and PPFIA4. Interacts with ERC1 (By similarity). Interacts with RAB3A, RAB3B and RAB3D that have been activated by GTP-binding. Interacts with RAB3C, RAB10, RAB26 and RAB37. Binds UNC13A.|||Cell membrane|||Phosphorylated by BRSK1.|||Presynaptic cell membrane|||Rab effector involved in exocytosis (PubMed:11797009). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (PubMed:11797009). Plays a role in dendrite formation by melanocytes (By similarity).|||Synapse http://togogenome.org/gene/10090:Doc2a ^@ http://purl.uniprot.org/uniprot/Q7TNF0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain and mast cells.|||C2 domain 1 is involved in binding calcium and phospholipids.|||Calcium sensor which most probably regulates fusion of vesicles with membranes. Binds calcium and phospholipids. May be involved in calcium dependent neurotransmitter release through the interaction with UNC13A. May be involved in calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.|||Interacts (via N-terminus) with UNC13A. Interacts with cytoplasmic dynein light chain DYNLT1 (By similarity). Interacts with UNC13D (By similarity).|||Lysosome|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Igsf1 ^@ http://purl.uniprot.org/uniprot/Q7TQA1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Expressed at embryonic day (E) 12.5 in embryo.|||Interacts with INHA; the interaction is not confirmed by standard receptor binding assays (By similarity). Interacts with ACVR1B; the interaction appears to be ligand-dependent as it is diminished by inhibin B and activin A. Interacts with ACVR2A, ACVR2B, ACVRL1 and BMPR1B (By similarity). Interacts with HECTD1 (By similarity).|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Membrane|||Mice are viable and fertile and show no alterations in FSH synthesis or secretion or in ovarian and testicular function. According to PubMed:23143598 male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations and increased body mass.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||Secreted|||Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B. Necessary to mediate a specific antagonistic effect of inhibin B on activin-stimulated transcription (By similarity). http://togogenome.org/gene/10090:Vgll1 ^@ http://purl.uniprot.org/uniprot/Q99NC0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the vestigial family.|||Interacts with TEFs.|||May act as a specific coactivator for the mammalian TEFs.|||Nucleus http://togogenome.org/gene/10090:Cdc123 ^@ http://purl.uniprot.org/uniprot/Q8CII2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CDC123 family.|||Cytoplasm|||Phosphorylated.|||Required for S phase entry of the cell cycle. http://togogenome.org/gene/10090:Taco1 ^@ http://purl.uniprot.org/uniprot/Q8K0Z7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a translational activator of mitochondrially-encoded cytochrome c oxidase 1.|||Belongs to the TACO1 family.|||Mitochondrion http://togogenome.org/gene/10090:Lig4 ^@ http://purl.uniprot.org/uniprot/Q8BTF7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP-dependent DNA ligase family.|||DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination. Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed. Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps. Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. LIG4 regulates nuclear localization of XRCC4.|||Embryonic lethality associated with extensive apoptotic cell death in the embryonic central nervous system.|||Interacts with XRCC4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry and XRCC4 is required for LIG4 stability. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with APLF.|||Nucleus http://togogenome.org/gene/10090:Ubr1 ^@ http://purl.uniprot.org/uniprot/O70481 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UBR1 family.|||Contaminating sequence. Potential poly-A sequence.|||E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. May be involved in pancreatic homeostasis. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (By similarity).|||Expressed in limb buds at 9.5-11.5 dpc.|||In models of cancer cachexia, induced in muscle during the progression of wasting.|||Interacts with RECQL4.|||Mice are viable and fertile, but show a decreased mass of skeletal muscle and adipose tissue. They have exocrine pancreatic insufficiency with impaired stimulus-secretion coupling and increased susceptibiliy to pancreatic injury. UBR1 and UBR2 double knockout embryos die at midgestation, with defects in neurogenesis and cardiovascular development. These defects included reduced proliferation as well as precocious migration and differentiation of neural progenitor cells.|||Present in skeletal muscle and liver (at protein level). Broadly expressed, with highest levels in skeletal muscle and heart. Expressed in acinar cells of the pancreas. In testes, expressed primarily in spermatogonia.|||The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif.|||The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides (By similarity).|||cytosol http://togogenome.org/gene/10090:Gemin5 ^@ http://purl.uniprot.org/uniprot/Q8BX17 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat gemin-5 family.|||Cytoplasm|||Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Interacts directly with SMN1, SNRPB, SNRPD1, SNRPD2, SNRPD3 and SNRPE. Identified in a SMN complex that contains GEMIN2/SIP1. Interacts with cytosolic DDX20/GEMIN3 and GEMIN4. Interacts with SNRNP70 and HNRNPU. Identified in a complex with 80S ribosomes; binds to the 60S large ribosomal subunit. Interacts with the ribosomal subunits RPL3 and RPL4.|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Within the SMN complex, GEMIN5 recognizes and delivers the small nuclear RNAs (snRNAs) to the SMN complex. Binds to the 7-methylguanosine cap of RNA molecules (By similarity). Binds to the 3'-UTR of SMN1 mRNA and regulates its translation; does not affect mRNA stability (PubMed:25911097). May play a role in the regulation of protein synthesis via its interaction with ribosomes (By similarity).|||The WD repeat domain mediates binding to U1 snRNA and to U4 snRNA. The WD repeat domain also mediates binding to the 7-methylguanosine cap that is found both on mRNA and snRNA molecules. The regions that bind snRNA molecules and the isolated 7-methylguanosine cap overlap at least partially. Besides, the WD repeat domain mediates interaction with the 60S large ribosomal subunit.|||gem|||nucleoplasm http://togogenome.org/gene/10090:Slc48a1 ^@ http://purl.uniprot.org/uniprot/Q9D8M3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HRG family.|||Deficient mice fed the standard laboratory rodent diet have peripheral blood counts that are all within the normal range, including the red cell indices. No differences between male and female animals. They show 15% increase in the size of the spleen in. Mutants have hemozoin beginning to accumulate in reticuloendothelial system macrophages 8 days after birth. They require more dietary iron to maintain erythropoiesis than littermate control animals.|||Endosome membrane|||Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment. In macrophages of the reticuloendothelial system, is the heme transporter for heme-iron recycling. Essential for macrophage iron homeostasis, transports heme from the phagolysosome to the cytoplasm during erythrophagocytosis (EP).|||Lysosome membrane|||Strongly expressed in macrophages of the reticuloendothelial system.|||phagosome membrane http://togogenome.org/gene/10090:Fam107b ^@ http://purl.uniprot.org/uniprot/Q3TGF2 ^@ Developmental Stage|||Induction|||Similarity|||Tissue Specificity ^@ Belongs to the FAM107 family.|||Expressed in the developing brain embryo. Expressed in the mesencephalon in the tectum at 12.5 dpc and in the inferior colliculus at 16.5 dpc until birth. Expressed in the telencephalon in the ventricular zone, cortical plate, ganglionic eminence and hippocampus from 14.5 to 18.5 dpc. Expressed in the rhombencephalon in the pontine nuclei and in the external granule layer of the cerebellum at 16.5 and 18.5 dpc.|||Expressed in the hippocampus and hypothalamus. Expressed in the pontine nuclei and reticulotegmental nucleus. Expressed in Purkinje cell and nuclear layers of the cerebelum. Expressed in the choroid plexus. Expressed in hippocampal granule neurons of the dente gyrus.|||Is not up-regulated in the hippocampus by acute social defeat stress or glucocorticoids stimulation. http://togogenome.org/gene/10090:Or10d4c ^@ http://purl.uniprot.org/uniprot/Q9EQ84 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Taf9 ^@ http://purl.uniprot.org/uniprot/Q8VI33 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AK6 and TAF9 were initially considered as products of the same gene since they share two exons. However, they are translated from different initiation codons and reading frames and encode unrelated proteins. This arrangement is conserved in some mammalian species.|||Belongs to the TAF9 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the TATA-binding protein-free TAF complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. The PCAF complex consists at least of TADA2L/ADA2, SUPT3H/SPT3, TADA3L/ADA3, TAF5L/PAF65-beta, TAF6L/PAF65-alpha, TAF10/TAFII30, TAF12/TAFII20, TAF9/TAFII31 and TRRAP. The STAGA transcription coactivator-HAT complex consists at least of SUPT3H, GCN5L2, SUPT7L, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Binds N-terminal domain of p53/TP53 which is essential for transcription. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Binds TFIIB and the Herpes simplex virus activator VP16. Forms a heterodimer with TAF6 in a complex with the TAF4B-TAF12 heterodimer. Also interacts with TAF5. Binds directly DNA. Increased DNA binding when complexed with TAF6.|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. TAF9 is also a component of the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TAF9 and its paralog TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. Essential for cell viability. May have a role in gene regulation associated with apoptosis. http://togogenome.org/gene/10090:Pcdhac2 ^@ http://purl.uniprot.org/uniprot/Q91Y09 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Sp5 ^@ http://purl.uniprot.org/uniprot/Q9JHX2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Binds to GC boxes promoters elements. Probable transcriptional activator that has a role in the coordination of changes in transcription required to generate pattern in the developing embryo.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Morc2b ^@ http://purl.uniprot.org/uniprot/Q8C5W4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ In juvenile testes, expression is absent prior to postnatal day 12, is detected at a low level at day 12, and increased significantly at day 14 and beyond. In adul testes, expressed in meiotic spermatocytes, abundant in post-meiotic haploid round spermatids, and absent from elongated spermatids.|||Interacts with Morc2a.|||Knockouts are viable and appear to be grossly normal. Mutant males and females show meiotic arrest and sterility. Males have significantly smaller testes than control males. Their testes weigh approximately 70% less than control testes. Their spermatocytes and oocytes exhibit failures in chromosomal synapsis, blockades in meiotic recombination, and increased apoptosis (PubMed:29329290). The ovaries of adult female mutant mice are much smaller than those from heterozygous littermates and are devoid of oocytes (PubMed:29329290).|||Nucleus|||Protein is abundant in testes but not detected in other adult tissues examined (at protein level). Detected in germ cells with a distinct developmental-specific expression pattern but not in somatic cells such as Sertoli cells.|||Required for chromosomal synapsis and meiotic recombination in males and females.|||Retrotransposed homolog of Morc2a. http://togogenome.org/gene/10090:Plod1 ^@ http://purl.uniprot.org/uniprot/Q9R0E2 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in the liver, heart, lung, skeletal muscle and kidney.|||Homodimer (By similarity). Identified in a complex with P3H3 and P3H4 (PubMed:27119146).|||Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (PubMed:27119146). Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (By similarity). These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links (PubMed:27119146).|||Rough endoplasmic reticulum membrane http://togogenome.org/gene/10090:Mrps2 ^@ http://purl.uniprot.org/uniprot/Q8BQ99|||http://purl.uniprot.org/uniprot/Q924T2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS2 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion|||Required for mitoribosome formation and stability, and mitochondrial translation. http://togogenome.org/gene/10090:Cfp ^@ http://purl.uniprot.org/uniprot/P11680 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ A positive regulator of the alternate pathway of complement (PubMed:28264884). It binds to and stabilizes the C3- and C5-convertase enzyme complexes (By similarity). Inhibits CFI-CFH mediated degradation of Inhibits CFI-CFH mediated degradation of Complement C3 beta chain (C3b) (By similarity).|||In plasma, properdin exists as dimers, trimers or tetramers in the relative proportions of 26:54:20 (By similarity). Interacts with the pro-C3-convertase enzyme complex (C3b-Bb) comprised of Complement C3 beta chain (C3b) and the Complement factor B Bb fragment (Bb), where it binds (via its TSP type-1 5 domain) with C3b and Bb (By similarity). This interaction stabilizes the complex and allows it to become the active C3-convertase enzyme complex (C3b-Bb-FP) (By similarity). Interacts with C3b (PubMed:28264884). Interacts with CFB (By similarity).|||Secreted|||TSP type-1 domain 0 binds to TSP type-1 domain 4, and TSP type-1 domain 1 binds to TSP type-1 domain 6 (By similarity). These interactions mediate multimerization (By similarity). http://togogenome.org/gene/10090:Tex264 ^@ http://purl.uniprot.org/uniprot/E9Q137 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Endoplasmic reticulum membrane|||Interacts (via the LIR motif) with ATG8 family proteins MAP1LC3A, MAP1LC3B, GABARAP and GABARAPL1. Interacts with VCP/p97; bridging VCP/p97 to covalent DNA-protein cross-links (DPCs). Interacts with TOP1 (when sumoylated).|||Major reticulophagy (also called ER-phagy) receptor that acts independently of other candidate reticulophagy receptors to remodel subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. The ATG8-containing isolation membrane (IM) cradles a tubular segment of TEX264-positive ER near a three-way junction, allowing the formation of a synapse of 2 juxtaposed membranes with trans interaction between the TEX264 and ATG8 proteins. Expansion of the IM would extend the capture of ER, possibly through a 'zipper-like' process involving continued trans TEX264-ATG8 interactions, until poorly understood mechanisms lead to the fission of relevant membranes and, ultimately, autophagosomal membrane closure. Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: acts by bridging VCP/p97 to covalent DNA-protein cross-links (DPCs) and initiating resolution of DPCs by SPRTN.|||Nucleus|||The LIR motif in the cytosol-facing C-terminal region is involved in the interaction with ATG8 proteins.|||The disordered region is required for autophagosome binding and reticulophagy, probably via bridging the long distance between endoplasmic reticulum and autophagosome membranes, because ribosomes exist on endoplasmic reticulum membranes that attach to autophagic membranes.|||autophagosome|||cytosol http://togogenome.org/gene/10090:Mtss2 ^@ http://purl.uniprot.org/uniprot/Q6P9S0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MTSS family.|||Cytoplasm|||Interacts (via IMD domain) with RAC1; this interaction may be important to potentiate PDGF-induced RAC1 activation.|||Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation. May function in actin bundling.|||ruffle http://togogenome.org/gene/10090:Slc26a7 ^@ http://purl.uniprot.org/uniprot/Q8R2Z3 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an anion channel mediating the transport of chloride, bromide, iodide, nitrate, sulfate, gluconate, thiocyanate and bicarbonate ions (PubMed:15591059, PubMed:24810589, PubMed:30333321, PubMed:32726161, PubMed:35788623). Its permeability towards bicarbonate is weak and increases when pH is above 7 (PubMed:15591059). Mediates oxalate transport (By similarity). Mediates thiocyanate transport in retinal pigment epithelium cells (PubMed:32726161). Mediates iodide transport in the thyroid gland, playing an important role in the synthesis of thyroid hormones and the maintenance of thyroid function (PubMed:30333321, PubMed:35788623). Although it is an anion channel, according to PubMed:12736153 and PubMed:19723628 it has been shown to exhibit chloride-bicarbonate exchanger activity.|||Although it is an anion channel, according to PubMed:12736153 and PubMed:19723628 it has been shown to exhibit chloride-bicarbonate exchanger activity.|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Expressed in the Reissner's membrane epithelial cells in the cochlea (at protein level) (PubMed:24810589). Expressed in the retinal pigment epithelium (at protein level) (PubMed:32726161). Abundantly expressed in parietal cells on the glandular portion of the stomach. Lower levels are observed in the kidney, with expression in the proximal tubule and thick ascending limb of the loop of Henle. Also expressed in distal segments of nephron, in extraglomerular mesagial cells and a subpopulation of intercalated cells of outer medullary collecting ducts. Expressed in the thyroid gland.|||Lateral cell membrane|||Mice develop goitrous congenital hypothyroidism, with enlarged thyroid gland and severely reduced T4 than T3 in the serum and thyroid gland (PubMed:30333321, PubMed:35788623). Animals fed a low iodine diet show more severe growth failure than those fed a normal diet (PubMed:35788623). Develop distal renal tubular acidosis, manifested by metabolic acidosis and alkaline urine pH and in the stomach, stimulated acid secretion is significantly impaired (PubMed:19723628). Retinal pigment epithelium cells (RPE) from Slc26a7 KO mice have a dramatically smaller whole cell SCN (-) conductance compared with wild-type RPE cells (PubMed:32726161).|||Recycling endosome membrane|||Regulated by pH. Activity inhibited by all inhibitors of several anion channels and transporters, including 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS), diphenylamine-2-carboxylic acid, glybenclamide and 5-Nitro-2-(3-phenylpropyl-amino)benzoic acid. http://togogenome.org/gene/10090:Nup98 ^@ http://purl.uniprot.org/uniprot/A0A140T8J8|||http://purl.uniprot.org/uniprot/A0A1B0GRA7|||http://purl.uniprot.org/uniprot/A0A1B0GRB5|||http://purl.uniprot.org/uniprot/A0A1B0GSX7|||http://purl.uniprot.org/uniprot/B2RQL0|||http://purl.uniprot.org/uniprot/Q3TPG3|||http://purl.uniprot.org/uniprot/Q3UJE5|||http://purl.uniprot.org/uniprot/Q6PFD9 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoproteolytically cleaved to yield Nup98 and Nup96 or Nup98 only, respectively. Cleaved Nup98 is necessary for the targeting of Nup98 to the nuclear pore and the interaction with Nup96.|||Belongs to the nucleoporin GLFG family.|||Contains G-L-F-G repeats. The FG repeat domains have a direct role in the transport (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Nucleus membrane|||Part of the nuclear pore complex (NPC). Interacts directly with NUP96. Part of the Nup160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and NUP96; this complex plays a role in RNA export and in tethering NUP98 and NUP153 to the nucleus. Interacts with RAE1. Does not interact with TPR (By similarity). Interacts directly with NUP88 and NUP214, subunits of the cytoplasmic filaments of the NPC (PubMed:22480613). Interacts (via N-terminus) with DHX9 (via DRBM, OB-fold and RGG domains); this interaction occurs in a RNA-dependent manner and stimulates DHX9-mediated ATPase activity (By similarity).|||Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC. May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes. Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body).|||nuclear pore complex|||nucleoplasm http://togogenome.org/gene/10090:Adprh ^@ http://purl.uniprot.org/uniprot/P54923|||http://purl.uniprot.org/uniprot/Q3U5N4 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the ADP-ribosylglycohydrolase family.|||Binds 2 magnesium ions per subunit.|||Monomer.|||Specifically acts as an arginine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to arginine residues on proteins.|||Synergistically stimulated by magnesium and dithiothreitol (DTT) in vitro. http://togogenome.org/gene/10090:Ttll8 ^@ http://purl.uniprot.org/uniprot/A4Q9F1 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Arg-403 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in testis (PubMed:17499049, PubMed:25180231). Expressed in brain, heart, kidney, liver, lung, muscle, spleen and trachea (PubMed:17499049, PubMed:25180231, PubMed:33414192). Expressed in sperm flagellum (PubMed:33414192). In the brain, specifically expressed in ependymal cilia (PubMed:23897886).|||Monoglycylase which modifies both tubulin and non-tubulin proteins, adding a single glycine on the gamma-carboxyl groups of specific glutamate residues to generate monoglycine side chains within the C-terminal tail of target proteins (PubMed:19524510, PubMed:28576883). Not involved in elongation step of the polyglycylation reaction (PubMed:19524510). Preferentially monoglycylates alpha-tubulin over beta-tubulin (PubMed:19524510). Together with TTLL3, mediates microtubule glycylation of primary and motile cilia, which is essential for their stability and maintenance (PubMed:19524510, PubMed:23897886, PubMed:25180231). Together with TTLL3, glycylates sperm flagella which regulates axonemal dynein motor activity, thereby controlling flagellar beat, directional sperm swimming and male fertility (PubMed:33414192). Monoglycylates non-tubulin proteins such as ANP32A, ANP32B, SET, NCL and NAP1 (PubMed:19524510, PubMed:19427864).|||Simultaneous TTLL3 and TTLL8 knockout mice are subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells.|||TTLL3 and TTLL8 monoglycylase-mediated glycylation of tubulin was initially reported to play a role in ependymal motile ciliary maintenance (PubMed:23897886). However, contradictory results were later observed (PubMed:33414192).|||Two conserved structural elements specific among monoglycylases, IS1 and IS2, are involved in glycyl chains initiation. Two conserved structural interfaces likely constitute the binding platforms for tubulin tail and microtubule.|||cilium|||cilium axoneme|||cytoskeleton|||flagellum axoneme http://togogenome.org/gene/10090:Bean1 ^@ http://purl.uniprot.org/uniprot/Q9EQG5 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts with NEDD4.|||Membrane http://togogenome.org/gene/10090:Adck1 ^@ http://purl.uniprot.org/uniprot/Q9D0L4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Appears to be essential for maintaining mitochondrial cristae formation and mitochondrial function by acting via YME1L1 in a kinase-independent manner to regulate essential mitochondrial structural proteins OPA1 and IMMT (By similarity). The action of this enzyme is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr) (Probable).|||Belongs to the protein kinase superfamily. ADCK protein kinase family.|||Secreted http://togogenome.org/gene/10090:1700017B05Rik ^@ http://purl.uniprot.org/uniprot/Q3TEI4 ^@ Miscellaneous ^@ May be due to competing donor splice site. http://togogenome.org/gene/10090:Dll4 ^@ http://purl.uniprot.org/uniprot/Q9JI71 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5, expressed within the retina outer neuroblastic layer.|||Cell membrane|||Conditional knockdowns in retinal progenitors have thinner retinas with occasional regions abnormally organized into rosette-like structures in the outer nuclear layer and an optic nerve with a reduced diameter.|||Expressed in vascular endothelium. Expressed in retina at least during embryogenesis.|||Interacts with NOTCH4. Interacts (via N-terminal DSL and MNNL domains) with NOTCH1 (via EGF-like domains).|||Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (By similarity). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (PubMed:22323600). During spinal cord neurogenesis, inhibits V2a interneuron fate (By similarity). http://togogenome.org/gene/10090:Tead4 ^@ http://purl.uniprot.org/uniprot/Q62296 ^@ Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By FGF-1, FGF-2, calf serum, platelet-derived growth factor-BB, and phorbol 12-myristate 13-acetate.|||Interacts with WWTR1/TAZ (By similarity). Interacts with YAP1.|||Nucleus|||Preferentially expressed in lung and in skeletal muscle.|||Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif (By similarity). Might play a role in the embryonic development of skeletal muscle.|||Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon. http://togogenome.org/gene/10090:Gprasp1 ^@ http://purl.uniprot.org/uniprot/Q5U4C1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GPRASP family.|||Cytoplasm|||Expressed in the brain, with higher expression in the hippocampus, hypothalamus and olfactory bulb.|||Interacts with cytoplasmic tails of a variety of G-protein coupled receptors such as delta opioid receptor/OPRD1, beta-2 adrenergic receptor/ADRB2 and D4 dopamine receptor/DRD4 as well as D2 dopamine receptor/DRD2. Interacts with PER1 (By similarity). Interacts with BECN2; the interaction is direct.|||Modulates lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors. Targets receptors for degradation in lysosomes via its interaction with BECN2. http://togogenome.org/gene/10090:Ppp1r32 ^@ http://purl.uniprot.org/uniprot/Q148A4 ^@ Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with PPP1CA.|||cilium http://togogenome.org/gene/10090:Cstl1 ^@ http://purl.uniprot.org/uniprot/Q80Y72 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Highly expressed in testis where it localizes to spermatogonium, spermatocyes and round spermatids. Not detected in spermatozoa. Also detected in epididymis, cerebrum and pituitary.|||In testis, expression levels increase from postnatal week 4 onwards with peak levels at postnatal week 8. Expression remains high thereafter.|||Secreted http://togogenome.org/gene/10090:Lce1f ^@ http://purl.uniprot.org/uniprot/B9EJP6|||http://purl.uniprot.org/uniprot/Q9D1I4 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Gsx2 ^@ http://purl.uniprot.org/uniprot/P31316 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ At 10.0 dpc, expressed in a band of primitive neuroepithelial cells in the neural tube, mesencephalon and telencephalon. At 11.5-13.5 dpc, expression is symmetrical, but tightly limited in areas of the forebrain, midbrain and hindbrain (PubMed:7619729). At 11 dpc, in the developing telencephalon, expressed at high levels in cells throughout the presumptive lateral ganglionic eminence (LGE), with an apparent ventral-to-dorsal gradient in expressing cell numbers. Positive cells are also scattered somewhat uniformly throughout the adjacent medial ganglionic eminence. At 12.5 dpc onward, exhibits a clear graded pattern of expression, with low levels found in cells located ventrally and the highest levels confined to those in the most dorsal portion of the LGE (at protein level) (PubMed:19709628). Expression decreases from 14.5 dpc on and becomes undetectable at 16.5 dpc (PubMed:7619729).|||Belongs to the Antp homeobox family.|||Nucleus|||Transcription factor that binds 5'-CNAATTAG-3' DNA sequence and regulates the expression of numerous genes including genes important for brain development (PubMed:7619729). During telencephalic development, causes ventralization of pallial progenitors and, depending on the developmental stage, specifies different neuronal fates. At early stages, necessary and sufficient to correctly specify the ventral lateral ganglionic eminence (LGE) and its major derivatives, the striatal projection neurons. At later stages, may specify LGE progenitors toward dorsal LGE fates, including olfactory bulb interneurons (PubMed:19709628). http://togogenome.org/gene/10090:Or10p21 ^@ http://purl.uniprot.org/uniprot/Q8VGC1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or14a259 ^@ http://purl.uniprot.org/uniprot/Q7TS02 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ipo7 ^@ http://purl.uniprot.org/uniprot/Q9EPL8 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Abundantly expressed in dental epithelial cells, with lower expression in dental mesenchymal cells of the lower molars at 12.5 and 18.5 dpc (at protein level) (PubMed:35922041). Weakly expressed in pre-odontoblasts and papilla cells, moderately expressed in polarizing odontoblasts and abundantly expressed in secretory and mature odontoblasts at birth (at protein level) (PubMed:35922041). Expressed in dental mesenchymal cells at birth (at protein level) (PubMed:34995814). Strongly expressed in differentiated odontoblasts of molars at 1, 3 and 9 days of age (at protein level) (PubMed:35922041).|||Belongs to the importin beta family.|||Cytoplasm|||Forms a heterodimer with KPNB1 (By similarity). Interacts with histone H1 (By similarity). Interacts with H2A, H2B, H3 and H4 histones (PubMed:11493596). Interacts with SNUPN and XPO1 (By similarity). Interacts with RPS7 and RPL5 (By similarity). Interacts with RPL23A (via BIB domain) (By similarity). Binds directly to nuclear pore complexes (By similarity). Interacts with SMAD4 and NUP93; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (By similarity). Interacts with phosphorylated SMAD2; the interaction facilitates translocation of SMAD2 to the nucleus (PubMed:33548622). Interacts with SRP19 (By similarity). Interacts with RUNX2; the interaction inhibits RUNX2 nuclear translocation in osteoblasts (PubMed:35922041). Interacts with HDAC6, DLX3 and KLF4; the interaction facilitates HDAC6, DLX3 and KLF4 nuclear translocation in dental papilla cells (PubMed:35922041).|||Functions in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously is thought to serve itself as receptor for nuclear localization signals (NLS) and to promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (By similarity). In association with KPNB1 mediates the nuclear import of H1 histone and the Ran-binding site of IPO7 is not required but synergizes with that of KPNB1 in importin/substrate complex dissociation (By similarity). Promotes odontoblast differentiation via promoting nuclear translocation of DLX3, KLF4, SMAD2, thereby facilitating the transcription of target genes that play a role in odontoblast differentiation (PubMed:33548622, PubMed:35922041). Facilitates BMP4-induced translocation of SMAD1 to the nucleus and recruitment to the MSX1 gene promoter, thereby promotes the expression of the odontogenic regulator MSX1 in dental mesenchymal cells (PubMed:34995814). Also promotes odontoblast differentiation by facilitating the nuclear translocation of HDAC6 and subsequent repression of RUNX2 expression (PubMed:35922041). Inhibits osteoblast differentiation by inhibiting nuclear translocation of RUNX2 and therefore inhibition of RUNX2 target gene transcription (PubMed:35922041). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (PubMed:11493596).|||Induced by odontoblastic differentiation in dental papilla cells.|||Nucleus http://togogenome.org/gene/10090:Glt1d1 ^@ http://purl.uniprot.org/uniprot/A4FUP9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.|||Secreted http://togogenome.org/gene/10090:Adgrg1 ^@ http://purl.uniprot.org/uniprot/Q8K209 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADGRG1 NT is proposed to inhibit receptor signaling; its interactions with extracellular ligands and /or homophilic ADGRG1 NT interactions may relieve the inhibition. Following ligand binding to the N-terminal fragment, the N-terminal fragment is released from the seven-transmembrane C-terminal fragment to unveil a new N-terminal stalk, which then stimulates G-protein-dependent signaling activity. The N-terminal stalk has also been shown to be dispensable for at least some G-protein-dependent signaling.|||Autoproteolytically cleaved into 2 fragments; the large extracellular N-terminal fragment and the membroune-bound C-terminal fragment predominantly remain associated and non-covalently linked.|||Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Cell membrane|||Cobblestone-like cortical malformation with defective pial basement membrane (BM), abnormal anchorage of radial glial endfeet, mislocalized Cajal-Retzius cells and neuronal overmigration. Severe malformation of the rostral cerebellum that develops perinatally. Granule cells from the rostral region show loss of adhesion to extracellular matrix molecules of the pial basement membrane. In ADGRG1 knockout mice, neurons overmigrate through breached pial basement membrane or undermigrate forming irregular cortical layers. Deficient mice shown disruption of seminiferous tubule formation and increased sterility (PubMed:20981830).|||Expressed in neural progenitor cells in fetal forbrain. Expressed in migrating neurons. Expressed in radial glial endfeet (at protein level) (PubMed:21768377). Expressed in peritubular myoid cells, Sertoli cells, and germ cells of the testis (PubMed:20981830).|||Membrane raft|||N-glycosylated. The secreted ADGRG1 N-terminal fragment is heavily glycosylated.|||Predominantly non-covalently linked heterodimer of the N-terminal and the C-terminal fragment. ADGRG1 NT self-associates in a trans-trans manner; the homophilic interaction enhances receptor signaling. ADGRG1 CT interacts with ARRB2; the interaction is impaired by ADGRG1 NT. Part of a GPCR-tetraspanin complex at least consisting of ADGRG1, CD81, eventually CD9, and GNA11 in which CD81 is enhancing the association of ADGRG1 with GNA11 (By similarity). Interacts with heparin; leading to the reduction of ADGRG1 shedding (PubMed:27068534). Interacts with COL3A1 (By similarity).|||Receptor involved in cell adhesion and probably in cell-cell interactions. Mediates cell matrix adhesion in developing neurons and hematopoietic stem cells. Receptor for collagen III/COL3A1 in the developing brain and involved in regulation of cortical development, specifically in maintenance of the pial basement membrane integrity and in cortical lamination (PubMed:21768377). Binding to the COL3A1 ligand inhibits neuronal migration and activates the RhoA pathway by coupling to GNA13 and possibly GNA12 (By similarity). Plays a role in the maintenance of hematopoietic stem cells and/or leukemia stem cells in bone marrow niche (PubMed:23478665). Plays a critical role in tumourigenesis (By similarity). Plays essential role in testis development (PubMed:20981830).|||Secreted|||Ubiquitinated. Undergoes polyubiquitination upon activation. http://togogenome.org/gene/10090:Mcpt4 ^@ http://purl.uniprot.org/uniprot/P21812 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Completely inhibited by serine protease inhibitors such as chymostatin, diisopropylfluorophosphate and phenylmethylsulfonyl fluoride, but not by p-tosyl-L-phenylalanine chloromethyl ketone, p-tosyl-L-lysine chloromethyl ketone, pepstatin, E-64, EDTA or o-phenanthroline. Also inhibited by lima bean trypsin inhibitor, soy bean trypsin inhibitor and human plasma alpha1-antichymotrypsin.|||Has chymotrypsin-like activity. Hydrolyzes the amide bonds of synthetic substrates having Tyr and Phe residues at the P1 position. Preferentially hydrolyzes the 'Tyr-4-|-Ile-5' bond of angiotensin I and the 'Phe-20-|-Ala-21' bond of amyloid beta-protein, and is less active towards the 'Phe-8-|-His-9' bond of angiotensin I and the 'Phe-4-|-Ala-5' and 'Tyr-10-|-Glu-11' bonds of amyloid beta-protein. Involved in thrombin regulation and fibronectin processing.|||Mice display an impaired ability to inactivate thrombin or degrade fibronectin in peritoneal cells.|||Monomer.|||Submucosal mast cells. In femoral muscle, detected in myocytes but not in mast cells. http://togogenome.org/gene/10090:Tmem68 ^@ http://purl.uniprot.org/uniprot/Q9D850 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acyltransferase that regulates cellular triglyceride (TG) content and glycerolipid composition via the monoglyceride pathway (PubMed:36768334). Primarily acyl-CoA:monoacylglycerol acyltransferase (MGAT), but can also exhibit acyl-CoA:diacylglycerol acyltransferase (DGAT) activity (PubMed:36768334). By regulating the synthesis of diglyceride precursors, it may affect the levels of glycerophospholipids such as phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine (PubMed:36768334). Plays a role in lipogenesis by inducing the expression of some key regulators such as diglyceride acyltransferases (DGATs) and enzymes of de novo fatty acid synthesis (PubMed:36768334).|||Belongs to the diacylglycerol acyltransferase family. Highly divergent.|||Endoplasmic reticulum membrane|||Widely expressed, with highest level in the brain, followed by lung and duodenum, and lowest levels in tongue, testis, skin and ileum. http://togogenome.org/gene/10090:Rps18 ^@ http://purl.uniprot.org/uniprot/P62270|||http://purl.uniprot.org/uniprot/Q561N5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS13 family.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the small ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Ism1 ^@ http://purl.uniprot.org/uniprot/V9GXR4 ^@ Similarity ^@ Belongs to the isthmin family. http://togogenome.org/gene/10090:Mt3 ^@ http://purl.uniprot.org/uniprot/P28184|||http://purl.uniprot.org/uniprot/Q3USP9 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the metallothionein superfamily. Type 1 family.|||Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro (By similarity).|||Brain.|||Metallothioneins have a high content of cysteine residues that bind various heavy metals. http://togogenome.org/gene/10090:Cfap206 ^@ http://purl.uniprot.org/uniprot/Q6PE87 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CFAP206 family.|||Essential for sperm motility and is involved in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract (PubMed:32376681). Required for the establishment of radial spokes in sperm flagella (PubMed:32376681).|||Expressed in the left-right organiser at embryonic day 8.0 dpc and at 17.5 dpc, expressed in the airway epithelia and brain ependymal tissues.|||Expressed in the sperm, oviduct, lung, nasal cavity, brain ependyma and choroid plexus.|||Mice postnatally develop hydrocephalus, show impaired mucociliary clearance of the airways and are characterized by male infertility.|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Tarsl2 ^@ http://purl.uniprot.org/uniprot/Q8BLY2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage.|||Cytoplasm|||May be a component of the multisynthetase complex (MSC), a large multi-subunit complex which contains at least eight different aminoacyl-tRNA synthetases plus three auxillary subunits AIMP1, AIMP2 and EEF1E1. Interacts with the MSC components EPRS1, AIMP1, AIMP2 and KARS1.|||Nucleus|||Ubiquitous (at protein level). Strongly expressed in muscle (at protein level). Moderately expressed in heart and liver (at protein level). Weakly expressed in stomach, kidney, testis, spleen, brain, fat and lung (at protein level). http://togogenome.org/gene/10090:Tmc7 ^@ http://purl.uniprot.org/uniprot/Q8C428 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMC family.|||Membrane|||Probable ion channel.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Pkhd1 ^@ http://purl.uniprot.org/uniprot/E9PZ36 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A mouse model, for human autosomal recessive polycystic kidney disease (ARPKD), where homozygous knockout mice for the Pkhd1 gene are born at a frequency lower than the expected Mendelian ratio (PubMed:18235088). Homozygous mice may lead to embryonic lethality (PubMed:18235088). Mice that escape embryonic lethality and survive into adulthood exhibit mild to severe tubular dilation or cyst formation in the kidney and liver accompanied by fibrosis and necrosis (PubMed:18235088). Homozygous mice for the Pkhd1 gene develop cysts and fibrosis in the liver at 1 month of age, and females develop proximal tubule (PT) dilation at 6 months of age whereas male mice never develop PT dilation (PubMed:22021705). Both male and female homozygous mice develop liver cysts and fibrosis at 3 months of age and this worsens with age until the liver is completely replaced by cysts at 12 mo of age (PubMed:22021705). A new mouse model, for ARPKD, where homozygous knockout mice for the Pkhd1 gene develop biliary dysgenesis accompanied by periportal fibrosis. Despite the progressive liver disease, these mice are viable at 12 months of age with no apparent decline in synthetic liver function. These mice also develop extrahepatic phenotypes involving the pancreas, extrahepatic bile ducts, and spleen, which occur in a more variable manner (PubMed:18202188). An other model, for ARPKD, where homozygous knockout mice for the Pkhd1 gene develop progressive renal cystic disease involving the proximal tubules, collecting ducts, and glomeruli. In the liver, mice show dilatation of the bile ducts and periportal fibrosis. Dilatation of pancreatic exocrine ducts is uniformly seen, with pancreatic cysts arising less frequently (PubMed:18286309).|||Apical cell membrane|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||Expressed in bile ducts and distal nephron segments but is absent from the proximal tubule (PubMed:18202188). Expressed in pancreas and kidney but also in the liver (PubMed:28729032). Expressed primarily in the distal tubule and thick ascending limb of the loop of Henle, and at low-level in the proximal tubule before renal development is complete at P0 (PubMed:28729032).|||Golgi apparatus|||Interacts with CAMLG (PubMed:16243292). Interacts with PKD2 (PubMed:18235088). Interacts (via CST) with ARF4; this interaction allows an efficient PKHD1 trafficking to the cilium (PubMed:24586199). Interacts (via CST) with RAB8A; this interaction controls trafficking through the endomembrane systeme and to the cilium (PubMed:20048263). Interacts (via CST) with TULP3; this interaction allows PKHD1 trafficking to the cilium (PubMed:28154160).|||N-glycosylated.|||Nucleus|||Palmitoylated (PubMed:20048263). Palmitoylation facilitates the trafficking to the cilia and membrane targeting (PubMed:20048263).|||Promotes ciliogenesis in renal epithelial cells and therefore participates in the tubules formation and/or ensures the maintenance of the architecture of the lumen of the kidney (PubMed:18235088, PubMed:20875407). Has an impact on cellular symmetry by ensuring correct bipolar cell division through the regulation of centrosome duplication and mitotic spindle assembly and by maintaining oriented cell division (OCD) during tubular elongation through planar cell polarity (PCP) pathway (PubMed:19959710). During epithelial cell morphogenesis regulates also cell-cell and cell-matrix adhesion and participates in cell motility (By similarity). Promotes cell-cell contact through the positive regulation of PTK2 kinase activity leading to either positive regulation of epithelial cell proliferation through the HRAS/RAF1 pathways, or negative regulation of apoptosis through the PDK1/AKT1 pathway (PubMed:20875407). May act in collecting-duct and biliary differentiation (By similarity). May participate in the regulation of the cholangiocytes proliferation and the CCN2 production in an CXCL8-dependent manner (By similarity).|||Secreted|||Several proteolytic cleavages occur within the extracellular domain, whereas at least one cleavage occurs within the cytoplasmic domain (PubMed:16956880). Cleaved by a probable proprotein convertase which produces an extracellular domain (polyductin extracellular domain, (PECD)) and a C-terminal fragment (polyductin transmembrane fragment (PTM)) which are tethered together by disulfide bonds (PubMed:17470460, PubMed:28729032). This extracellular domain (PECD) is then shed from the primary cilium by activation of a member of the ADAM metalloproteinase disintegrins family, resulting in concomitant release of an intra-cellular C-terminal fragment (ICD) via a gamma-secretase-dependent process (PubMed:17470460, PubMed:28729032). The proteolytic cleavage of the C-terminal intracellular fragment (ICD) is controlled by cytosolic calcium concentration and activation of PKC (PubMed:16956880).|||centromere|||cilium|||cilium basal body|||extracellular exosome|||spindle http://togogenome.org/gene/10090:Cdk12 ^@ http://purl.uniprot.org/uniprot/Q14AX6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors.|||Interacts with CCNL1 and CCNL2.|||Nucleus|||Nucleus speckle|||Phosphorylation at Thr-889 increases kinase activity. http://togogenome.org/gene/10090:Ube3a ^@ http://purl.uniprot.org/uniprot/O08759 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cysteine residue is required for ubiquitin-thioester formation.|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:20211139, PubMed:24728990, PubMed:30020076). Several substrates have been identified including the BMAL1, ARC, LAMTOR1, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B (PubMed:20211139, PubMed:24728990, PubMed:30020076). Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo (By similarity). Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component BMAL1, leading to its proteasomal degradation (PubMed:24728990). Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (PubMed:20211139). Required for synaptic remodeling in neurons by mediating ubiquitination and degradation of LAMTOR1, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (PubMed:30020076). Synergizes with WBP2 in enhancing PGR activity (By similarity).|||Mice with maternal deficiency display autism spectrum disorders, characterized by motor dysfunction, inducible seizures and a context-dependent learning deficit (PubMed:9808466, PubMed:11895368). Long-term potentiation (LTP) is severely impaired despite normal baseline synaptic transmission and neuroanatomy (PubMed:9808466). The cytoplasmic abundance of p53/TP53 is increased in postmitotic neurons (PubMed:9808466). Accumulation of ARC protein in neurons, resulting in the excessive internalization of AMPA receptors (AMPARs) at synapses and impaired synaptic function (PubMed:20211139).|||Nucleus|||Phosphorylation at Tyr-654 by ABL1 impairs E3 ligase activity.|||The Ube3a locus is imprinted with silencing of the paternal allele in hippocampus and cerebellum in mice.|||The active form is probably a homotrimer. Binds UBQLN1 and UBQLN2. Interacts with the 26S proteasome. Interacts with BPY2. Interacts with HIF1AN, MAPK6 and NEURL4; interaction with MAPK6 may be mediated by NEURL4. Interacts with the proteasomal subunit PSMD4. Interacts with BMAL1 (PubMed:24728990). Interacts with ARC (PubMed:20211139). Interacts with ESR1 and WBP2 (By similarity).|||Up-regulated in response to neuronal activity.|||Widely expressed. Most abundant in brain, heart and thymus. http://togogenome.org/gene/10090:Polr2i ^@ http://purl.uniprot.org/uniprot/P60898 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.|||Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template (By similarity).|||nucleolus http://togogenome.org/gene/10090:Sik3 ^@ http://purl.uniprot.org/uniprot/Q6P4S6 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-221.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Binds to and is activated by YWHAZ when phosphorylated on Thr-221 (By similarity). Interacts with 14-3-3 proteins (By similarity). Interacts with HDAC4; this interaction leads to HDAC4 retention in the cytoplasm (PubMed:22318228). Interacts with DEPTOR, MLST8/GbetaL, RICTOR and RPTOR (By similarity).|||Cytoplasm|||Expressed in hypertrophic chondrocytes in the growth plate.|||In the embryo, detected at 15.5 dpc in both prehypertrophic and hypertrophic chondrocytes in developing bones (PubMed:22318228). At postnatal day 1 (P1), in cartilage growth plate, expressed in early proliferating and prehypertrophic chondrocytes. This expression pattern is maintained at least until P21 (at protein level) (PubMed:30232230).|||Mutant mice are born at the expected Mendelian rate, but 90% die on the first day after birth. The surviving animals show dwarfism throughout their postnatal life. They exhibit marked expansion of the growth plate and articular cartilage regions in the limbs, accumulation of chondrocytes in the sternum, ribs and spine, and impaired skull bone formation. Although chondrocyte hypertrophy and bone mineralization are markedly delayed, the body size is unaffected during embryogenesis, dwarfism appears as animals age.|||Phosphorylated at Thr-221 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.|||Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor (By similarity). Required for chondrocyte hypertrophy during skeletogenesis (PubMed:22318228). Negatively regulates cAMP signaling pathway possibly by acting on CRTC2/TORC2 and CRTC3/TORC3 (By similarity). Prevents HDAC4 translocation to the nucleus (PubMed:22318228). http://togogenome.org/gene/10090:Fbrs ^@ http://purl.uniprot.org/uniprot/Q8R089 ^@ Caution|||Sequence Caution ^@ Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Prakash et al. cloned a partial cDNA corresponding to the 3'UTR of the last exon of the gene (PubMed:7892239). They have shown that a synthetic peptide derived from this sequence could stimulate fibroblasts growth in vitro, and that this protein could be a fibrogenic lymphokine, that could stimulate several biological activities related to scarring. It would be expressed several cell types including CD4+ lymphocytes and fibroblasts. However, it was not confirmed by in vivo data. http://togogenome.org/gene/10090:Neurl3 ^@ http://purl.uniprot.org/uniprot/Q8CJC5 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that plays a role in various biological processes such as lung development or innate immunity (PubMed:15936721, PubMed:35792897). Seems to utilize UBE2E1. Promotes innate antiviral response by catalyzing 'Lys-63'-linked ubiquitination of IRF7 (PubMed:35792897).|||Expressed in alveolar epithelial type II cells.|||Induced in lung during endotoxemia. By LPS and inflammatory cytokines in alveolar epithelial type II cells.|||Mutant mice produce less type I IFNs and exhibit increased susceptibility to viral infection. http://togogenome.org/gene/10090:Immt ^@ http://purl.uniprot.org/uniprot/E9Q800|||http://purl.uniprot.org/uniprot/E9QAY6|||http://purl.uniprot.org/uniprot/Q3TEY5|||http://purl.uniprot.org/uniprot/Q3TVZ5|||http://purl.uniprot.org/uniprot/Q3U7N2|||http://purl.uniprot.org/uniprot/Q8CAQ8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MICOS complex subunit Mic60 family.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13 (By similarity). This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9 (By similarity). The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex (By similarity). Interacts with MICOS13/MIC13, MICOS10/MIC10, CHCHD6/MIC25, SAMM50 and TMEM11 (By similarity). Interacts with CHCHD3/MIC19 (PubMed:21081504). Interacts with APOO/MIC23/MIC26 and APOOL/MIC27 (By similarity). Interacts with HSPA1A/HSPA1B and OPA1, preferentially with the soluble OPA1 form (PubMed:21081504). Interacts with ARMC1 (By similarity). Interacts with ARMC12 (PubMed:33536340).|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.|||May be due to intron retention.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cyp1b1 ^@ http://purl.uniprot.org/uniprot/Q64429 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (By similarity). Exhibits catalytic activity for the formation of hydroxyestrogens from 17beta-estradiol (E2), namely 2- and 4-hydroxy E2 (PubMed:23821647). Metabolizes testosterone and progesterone to B or D ring hydroxylated metabolites (By similarity). May act as a major enzyme for all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:15258110). Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EpETrE) regioisomers, 8,9-, 11,12-, and 14,15- EpETrE, that function as lipid mediators in the vascular system (PubMed:15258110). Additionally, displays dehydratase activity toward oxygenated eicosanoids hydroperoxyeicosatetraenoates (HpETEs). This activity is independent of cytochrome P450 reductase, NADPH, and O2 (By similarity). Also involved in the oxidative metabolism of xenobiotics, particularly converting polycyclic aromatic hydrocarbons and heterocyclic aryl amines procarcinogens to DNA-damaging products (By similarity). Plays an important role in retinal vascular development. Under ambient/hyperoxic O2 conditions, promotes angiogenesis and capillary morphogenesis of retinal endothelial cells and pericytes, likely by metabolizing the oxygenated products symptomatic of oxidative stress (PubMed:19005183, PubMed:20032512, PubMed:23568032). Also, contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression (PubMed:23979599).|||Belongs to the cytochrome P450 family.|||Constitutively expressed in retinal and kidney pericytes cells (PubMed:23568032). Expressed in retinal endothelial cells (at protein level). Expressed in cardiac, pulmonary and aortic endothelial cells (PubMed:19005183). Constitutively expressed in trabecular meshwork of the eye (at protein level) (PubMed:23979599).|||Endoplasmic reticulum membrane|||Enzyme activity is increased by cytochrome b5 (PubMed:23821647). Enzyme activity is increased by liposomes containing anionic phospholipids, phosphatidic acid and cardiolipin. Inhibited by naringenin with an IC(50) of 5 uM (By similarity).|||Microsome membrane|||Mitochondrion|||Severe ocular drainage structure abnormalities, significant elevated intraocular pressure.|||Up-regulated by polycyclic aromatic hydrocarbons (PAH) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). http://togogenome.org/gene/10090:Btla ^@ http://purl.uniprot.org/uniprot/Q7TSA3 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in splenic T- and B-cells as well as lymph node tissues but very weakly in somatic tissues. Also expressed in macrophages, NK cells and dendritic cells. A polymorphic tissue distribution between several strains is seen.|||Inhibitory receptor on lymphocytes that negatively regulates antigen receptor signaling via PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:12796776, PubMed:14652006). May interact in cis (on the same cell) or in trans (on other cells) with TNFRSF14 (PubMed:19915044). In cis interactions, appears to play an immune regulatory role inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, can predominate during adaptive immune response to provide survival signals to effector T cells (PubMed:19915044).|||Interacts with tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:12796776, PubMed:14652006). Interacts with TNFRSF14/HVEM (via cysteine-rich domain 1) (PubMed:19915044).|||Mice exhibit no developmental defects in T- or B-cells in thymus or bone marrow, but increased antibody responses and sensitivity to antigen-induced 'experimental autoimmune encephalomyelitis'. T-cells lacking Btla show increased proliferation with a heightened response to anti-CD3 and a slightly greater response to stimulation with anti-IgM.|||N-glycosylated.|||Phosphorylated on Tyr residues by TNFRSF14 and by antigen receptors cross-linking, both inducing association with PTPN6 and PTPN11. http://togogenome.org/gene/10090:Eaf1 ^@ http://purl.uniprot.org/uniprot/Q9D4C5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional transactivator of ELL and ELL2 elongation activities.|||Belongs to the EAF family.|||Cajal body|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with ELL and ELL2 (By similarity).|||Nucleus speckle http://togogenome.org/gene/10090:Sult2a7 ^@ http://purl.uniprot.org/uniprot/K7N6K8 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Poldip2 ^@ http://purl.uniprot.org/uniprot/Q91VA6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with PCNA and POLD2. Interacts with SSBP1. Interacts with PRIMPOL; leading to enhance DNA polymerase activity of PRIMPOL. Interacts with POLH. Interacts with POLD1; leading to stimulate DNA polymerase activity of POLD1.|||Involved in DNA damage tolerance by regulating translesion synthesis (TLS) of templates carrying DNA damage lesions such as 8oxoG and abasic sites. May act by stimulating activity of DNA polymerases involved in TLS, such as PRIMPOL and polymerase delta (POLD1).|||Mitochondrion matrix|||Nucleus http://togogenome.org/gene/10090:Rab17 ^@ http://purl.uniprot.org/uniprot/P35292 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Expressed in kidney, liver, and intestine mainly by epithelial cells. Expressed in hippocampus (at protein level).|||Expression starts at 5 dpc and gradually increases from P5 to adulthood (at protein level).|||Melanosome|||Recycling endosome membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in transcytosis, the directed movement of endocytosed material through the cell and its exocytosis from the plasma membrane at the opposite side. Mainly observed in epithelial cells, transcytosis mediates for instance, the transcellular transport of immunoglobulins from the basolateral surface to the apical surface. Most probably controls membrane trafficking through apical recycling endosomes in a post-endocytic step of transcytosis. Required for melanosome transport and release from melanocytes, it also regulates dendrite and dendritic spine development. May also play a role in cell migration.|||dendrite http://togogenome.org/gene/10090:Mospd3 ^@ http://purl.uniprot.org/uniprot/Q05DT5|||http://purl.uniprot.org/uniprot/Q8BGG6 ^@ Disease Annotation|||Subcellular Location Annotation|||Tissue Specificity ^@ Defects in Mospd3 are a cause of defects of the right heart ventricle and of high mortality in newborns.|||Detected in heart, kidney, liver, spleen and brain.|||Membrane http://togogenome.org/gene/10090:Hdhd2 ^@ http://purl.uniprot.org/uniprot/Q3UGR5 ^@ Cofactor|||Similarity ^@ Belongs to the HAD-like hydrolase superfamily.|||Binds 1 Mg(2+) ion per subunit. http://togogenome.org/gene/10090:Cracr2a ^@ http://purl.uniprot.org/uniprot/Q3UP38 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in T helper 1 and T helper 17 cells.|||Belongs to the EFCAB4 family.|||Ca(2+)-binding protein that plays a key role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation. Acts as a cytoplasmic calcium-sensor that facilitates the clustering of ORAI1 and STIM1 at the junctional regions between the plasma membrane and the endoplasmic reticulum upon low Ca(2+) concentration. It thereby regulates CRAC channel activation, including translocation and clustering of ORAI1 and STIM1. Upon increase of cytoplasmic Ca(2+) resulting from opening of CRAC channels, dissociates from ORAI1 and STIM1, thereby destabilizing the ORAI1-STIM1 complex (By similarity).|||Cell membrane|||Cytoplasm|||Expressed in lymphoid organs including spleen and lymph nodes (PubMed:27016526). Abundantly expressed in T helper 1 and T helper 17 cells (PubMed:29987160).|||Golgi apparatus membrane|||Interacts with DYNC1H1 and VAV1 (By similarity). Interacts with the dynein-dynactin complex in a Ca(2+)-dependent manner (By similarity).|||Interacts with ORAI1 and STIM1; the interaction is direct and takes place in absence of Ca(2+). Forms a complex with ORAI1 and STIM1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations. Interacts with ORAI2 and ORAI3.|||Rab GTPase that mediates the trafficking of Weibel-Palade bodies (WPBs) to microtubule organizing center (MTOC) in endothelial cells in response to acute inflammatory stimuli (By similarity). During histamine (but not thrombin) stimulation of endothelial cells, the dynein-bound form induces retrograde transport of a subset of WPBs along microtubules to the MTOC in a Ca(2+)-independent manner and its GTPase activity is essential for this function (By similarity). Ca(2+)-regulated dynein adapter protein that activates dynein-mediated transport and dynein-dynactin motility on microtubules and regulates endosomal trafficking of CD47 (By similarity). Acts as an intracellular signaling module bridging two important T-cell receptor (TCR) signaling pathways, Ca(2+)-NFAT and JNK, to affect T-cell activation (PubMed:27016526). In resting T-cells, is predominantly localized near TGN network in a GTP-bound form, upon TCR stimulation, localizes at the immunological synapse via interaction with VAV1 to activate downstream Ca(2+)-NFAT and JNK signaling pathways (By similarity). Plays a role in T-helper 1 (Th1) cell differentiation and T-helper 17 (Th17) cell effector function (PubMed:29987160). Plays a role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation (By similarity).|||Vesicle|||microtubule organizing center|||trans-Golgi network membrane http://togogenome.org/gene/10090:Or2ak6 ^@ http://purl.uniprot.org/uniprot/L7MTY4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnh7 ^@ http://purl.uniprot.org/uniprot/Q9ER47 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.3/KCNH7 sub-subfamily.|||Membrane|||Pore-forming (alpha) subunit of voltage-gated potassium channel (By similarity). Channel properties may be modulated by cAMP and subunit assembly.|||The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH2/ERG1 and KCNH6/ERG2 (By similarity).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Pf4 ^@ http://purl.uniprot.org/uniprot/Q3TVN6|||http://purl.uniprot.org/uniprot/Q6P8R3|||http://purl.uniprot.org/uniprot/Q9Z126 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Homotetramer. Interacts with TNFAIP6 (via Link domain).|||Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Chemotactic for neutrophils and monocytes. Inhibits endothelial cell proliferation (By similarity).|||Secreted http://togogenome.org/gene/10090:Nr5a1 ^@ http://purl.uniprot.org/uniprot/P33242 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation stimulates the transcriptional activity.|||Belongs to the nuclear hormone receptor family. NR5 subfamily.|||Binds DNA as a monomer (By similarity). Part of a complex consisting of SFPQ, NONO and NR5A1. Interacts with DGKQ and CDK7 (By similarity). Interacts with NR0B2, NCOA2 and PPARGC1A. Binds to and activated by HIPK3.|||Expressed during early embryonic development. Expressed only in undifferentiated embryonal carcinoma cells.|||Nucleus|||Phosphorylated on Ser-203 by CDK7. This phosphorylation promotes transcriptional activity (By similarity).|||Sumoylation reduces CDK7-mediated phosphorylation on Ser-203.|||Transcriptional activator. Seems to be essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (By similarity). Transcription repressor of the Moloney leukemia virus long terminal repeat in undifferentiated murine embryonal carcinoma cells. Binds phosphatidylcholine and phospholipids with a phosphatidylinositol (PI) headgroup, in particular phosphatidyl(3,4)bisphosphate, phosphatidyl(3,5)bisphosphate and phosphatidyl(3,4,5)triphosphate. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. http://togogenome.org/gene/10090:Poln ^@ http://purl.uniprot.org/uniprot/Q7TQ07 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-A family.|||DNA polymerase with very low fidelity that catalyzes considerable misincorporation by inserting dTTP opposite a G template, and dGTP opposite a T template. Is the least accurate of the DNA polymerase A family (i.e. POLG, POLN and POLQ). Can perform accurate translesion DNA synthesis (TLS) past a 5S-thymine glycol. Can perform efficient strand displacement past a nick or a gap and gives rise to an amount of product similar to that on non-damaged template. Has no exonuclease activity. Error-prone DNA polymerase that preferentially misincorporates dT regardless of template sequence. May play a role in TLS during interstrand cross-link (ICL) repair. May be involved in TLS when genomic replication is blocked by extremely large major groove DNA lesions. May function in the bypass of some DNA-protein and DNA-DNA cross-links. May have a role in cellular tolerance to DNA cross-linking agents. Involved in the repair of DNA cross-links and double-strand break (DSB) resistance. Participates in FANCD2-mediated repair. Forms a complex with HELQ helicase that participates in homologous recombination (HR) repair and is essential for cellular protection against DNA cross-links.|||Expressed only in testis namely in primary spermatocytes and in round spermatids.|||Inhibited by ddTTP.|||Interacts with FANCD2, FANCI, PCNA, RAD51 and HELQ.|||Nucleus http://togogenome.org/gene/10090:Vmn1r8 ^@ http://purl.uniprot.org/uniprot/Q8R2C2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrpl44 ^@ http://purl.uniprot.org/uniprot/Q9CY73 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ribonuclease III family. Mitochondrion-specific ribosomal protein mL44 subfamily.|||Component of the 39S subunit of mitochondrial ribosome. May have a function in the assembly/stability of nascent mitochondrial polypeptides exiting the ribosome.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Stc1 ^@ http://purl.uniprot.org/uniprot/O55183|||http://purl.uniprot.org/uniprot/Q3UEW5|||http://purl.uniprot.org/uniprot/Q3UYZ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the stanniocalcin family.|||Expressed in many tissues.|||Homodimer; disulfide-linked.|||Secreted|||Stimulates renal phosphate reabsorption, and could therefore prevent hypercalcemia. http://togogenome.org/gene/10090:Pga5 ^@ http://purl.uniprot.org/uniprot/Q9D106 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase A1 family.|||Expressed in glandular chief cells of the neonatal stomach. Expressed in yolk sacs of the placenta (at protein level).|||In neonatal stomach, highly expressed for the first two weeks after birth, with rapidly decreasing expression after 17.5 days. In placenta, detected from 11.5 dpc until term.|||Inhibited by pepstatin A.|||Secreted|||Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent (By similarity). May play a role as a specialized neonatal digestive enzyme (Probable). http://togogenome.org/gene/10090:Phkb ^@ http://purl.uniprot.org/uniprot/Q7TSH2 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.|||Belongs to the phosphorylase b kinase regulatory chain family.|||By phosphorylation of various serine residues.|||Cell membrane|||Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin (By similarity).|||Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation (By similarity). http://togogenome.org/gene/10090:Cers3 ^@ http://purl.uniprot.org/uniprot/Q1A3B0 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward very- and ultra-long-chain fatty acyl-CoA (chain length greater than C22) (PubMed:16753040, PubMed:18541923, PubMed:22038835). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:16753040, PubMed:18541923, PubMed:22038835). It is crucial for the synthesis of ultra-long-chain ceramides in the epidermis, to maintain epidermal lipid homeostasis and terminal differentiation (PubMed:22038835).|||Contains a predicted homeobox domain which is degenerated, lacking residues important for DNA-binding. Moreover, the protein localizes in the endoplasmic reticulum and not in the nucleus, which also argues against homeobox function (PubMed:22038835).|||Endoplasmic reticulum membrane|||Newborn mice die shortly after birth from transepidermal water loss (PubMed:22038835). Defects are due to a complete loss of ultra long chain (more than C26:0) ceramides (PubMed:22038835). Newborn skin appears unwrinkled, erythematous and sticky (PubMed:22038835). Skin is also prone to C.albicans infection (PubMed:22038835).|||Predominantly expressed in testis (PubMed:16753040). In skin, present in the upper stratum spinosum and stratum granulosum (at protein level) (PubMed:22038835). http://togogenome.org/gene/10090:Or52r1 ^@ http://purl.uniprot.org/uniprot/Q8VGZ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or3a1d ^@ http://purl.uniprot.org/uniprot/Q7TRW8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r53 ^@ http://purl.uniprot.org/uniprot/A2RS76 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cplane2 ^@ http://purl.uniprot.org/uniprot/A2A825|||http://purl.uniprot.org/uniprot/B2RWG6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Potential effector of the planar cell polarity signaling pathway. Plays a role in targeted membrane trafficking most probably at the level of vesicle fusion with membranes. Involved in cilium biogenesis by regulating the transport of cargo proteins to the basal body and to the apical tips of cilia. More generally involved in exocytosis in secretory cells (By similarity).|||Potential effector of the planar cell polarity signaling pathway. Plays a role in targeted membrane trafficking most probably at the level of vesicle fusion with membranes. Involved in cilium biogenesis by regulating the transport of cargo proteins to the basal body and to the apical tips of cilia. More generally involved in exocytosis in secretory cells.|||cilium basal body http://togogenome.org/gene/10090:Cdh20 ^@ http://purl.uniprot.org/uniprot/Q9Z0M3 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types (By similarity).|||Cell membrane|||Expressed during embryogenesis.|||Expressed in brain. Highest level of expression in the retina. In embryo it is synthesized by the forebrain, anterior neural ridge, developing visual system, primitive external granular layer of the cerebellum and a subset of neural crest cells likely to develop into melanoblasts.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Nkain3 ^@ http://purl.uniprot.org/uniprot/Q3URJ8 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKAIN family.|||Cell membrane|||Detected in the brain only and specifically in neurons. Expressed in multiple regions such as cerebral cortex, thalamus, hippocampus, olfactory bulb and brainstem as well as in cerebellum with low expression in granular cell layer.|||Interacts with ATP1B1. http://togogenome.org/gene/10090:Gmfb ^@ http://purl.uniprot.org/uniprot/Q9CQI3 ^@ Function|||PTM|||Similarity ^@ Belongs to the actin-binding proteins ADF family. GMF subfamily.|||Phosphorylated; stimulated by phorbol ester.|||This protein causes differentiation of brain cells, stimulation of neural regeneration, and inhibition of proliferation of tumor cells. http://togogenome.org/gene/10090:Kif27 ^@ http://purl.uniprot.org/uniprot/Q7M6Z4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIF27 subfamily.|||Interacts with STK36.|||Plays an essential role in motile ciliogenesis.|||cilium|||cytoskeleton http://togogenome.org/gene/10090:Slc35f5 ^@ http://purl.uniprot.org/uniprot/Q8R314 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC35F solute transporter family.|||Membrane|||Putative solute transporter. http://togogenome.org/gene/10090:Paf1 ^@ http://purl.uniprot.org/uniprot/Q8K2T8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PAF1 family.|||Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. Connects PAF1C with the RNF20/40 E3 ubiquitin-protein ligase complex. Involved in polyadenylation of mRNA precursors (By similarity).|||Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. The PAF1 complex interacts with PHF5A (PubMed:27749823). Interacts with POLR2A, TCEA1, SKIC3, KMT2A/MLL1, SUPT5H, RNF20 and RNF40. Interacts with UBE2E1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ddx52 ^@ http://purl.uniprot.org/uniprot/Q3TKX4|||http://purl.uniprot.org/uniprot/Q8K301 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DEAD box helicase family. DDX52/ROK1 subfamily.|||Required for efficient ribosome biogenesis. May control cell cycle progression by regulating translation of mRNAs that contain a terminal oligo pyrimidine (TOP) motif in their 5' UTRs, such as GTPBP4.|||nucleolus http://togogenome.org/gene/10090:Hars2 ^@ http://purl.uniprot.org/uniprot/G5E823|||http://purl.uniprot.org/uniprot/Q99KK9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Homodimer.|||Mitochondrial aminoacyl-tRNA synthetase that catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP).|||Mitochondrion http://togogenome.org/gene/10090:Gtf2h5 ^@ http://purl.uniprot.org/uniprot/Q8K2X8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with the vesicular stomatitis virus matrix protein/M; this interaction may lead to transcription inhibition.|||Belongs to the TFB5 family.|||Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription.|||Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. Necessary for the stability of the TFIIH complex and for the presence of normal levels of TFIIH in the cell.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Lipk ^@ http://purl.uniprot.org/uniprot/Q8BM14 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Plays a highly specific role in the last step of keratinocyte differentiation. May have an essential function in lipid metabolism of the most differentiated epidermal layers (By similarity).|||Secreted http://togogenome.org/gene/10090:Kcna4 ^@ http://purl.uniprot.org/uniprot/Q61423 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily.|||Cell membrane|||Expressed in the brain, lens and retina.|||Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Binds PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (By similarity).|||The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:8020965). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:8020965). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity).|||axon http://togogenome.org/gene/10090:Anxa9 ^@ http://purl.uniprot.org/uniprot/Q9JHQ0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the annexin family.|||Homodimer.|||May act as a low affinity receptor for acetylcholine. http://togogenome.org/gene/10090:Or4k2 ^@ http://purl.uniprot.org/uniprot/E9Q8M3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Syce3 ^@ http://purl.uniprot.org/uniprot/B5KM66 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expression in pubertal testes is first detected at day 12 coinciding with the onset of prophase I of meiosis (at protein level). Expression in spermatocytes first detected during zygotene when synapsis is initiated and persists on synapsed regions of homologous chromosomes until diplotene. In pachytene oocytes expression is also localized to synapsed chromosomes.|||Expression is restricted to spermatocytes and is absent in spermatogonia, spermatids and spermatogonia (at protein level). Expressed in adult testis and embryonic ovary. Expressed in the convoluted seminiferous tubules in spermatogonia and spermatocytes.|||Homodimer (PubMed:25394919). Interacts with SYCE1 (PubMed:21637789, PubMed:25394919). Interacts with SYCE2 (PubMed:21637789). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (PubMed:31437213). Interacts with SPO16 (PubMed:30949703).|||Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Required for chromosome loading of the central element-specific SCS proteins, and for initiating synapsis between homologous chromosomes. Chromosome loading appears to require SYCP1. Required for fertility. May play a role in apoptosis of spermatogenic cells and pathogenesis of cryptorchidism.|||Mutant mice are characterized by infertility in both sexes as well as complete disruption of synapsis initiation resulting in meiotic arrest. Initiation of meiotic recombination appears normal, but its progression is severely impaired resulting in complete absence of Mlh1 foci.|||Nucleus|||Up-regulated in cryptorchid testes. http://togogenome.org/gene/10090:Ccnb3 ^@ http://purl.uniprot.org/uniprot/A2AEP2 ^@ Similarity ^@ Belongs to the cyclin family. http://togogenome.org/gene/10090:Uqcrb ^@ http://purl.uniprot.org/uniprot/Q9CQB4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UQCRB/QCR7 family.|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ucn3 ^@ http://purl.uniprot.org/uniprot/Q3UFJ9|||http://purl.uniprot.org/uniprot/Q924A4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.|||Binds with high affinity to CRF receptors 2-alpha and 2-beta.|||Expressed in some areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin.|||Secreted|||Suppresses food intake, delays gastric emptying and decreases heat-induced edema. Might represent an endogenous ligand for maintaining homeostasis after stress (By similarity).|||Suppresses food intake, delays gastric emptying and decreases heat-induced edema. Might represent an endogenous ligand for maintaining homeostasis after stress. http://togogenome.org/gene/10090:Rpl37a ^@ http://purl.uniprot.org/uniprot/P61514|||http://purl.uniprot.org/uniprot/Q4VAF2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL43 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Alkbh5 ^@ http://purl.uniprot.org/uniprot/Q3TSG4 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:29279410). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (By similarity). Requires molecular oxygen, alpha-ketoglutarate and iron (By similarity). Demethylation of m6A mRNA affects mRNA processing and export (By similarity). Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (PubMed:23177736, PubMed:29279410).|||Mice are viable, anatomically normal and reach adulthood but display impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes (PubMed:23177736, PubMed:29279410). Testes are significantly smaller and histological analysis of testis sections reveal aberrant tubular architecture and size (PubMed:23177736, PubMed:29279410). The number of spermatozoa released from cauda epididymes is dramatically reduced, and the spermatozoa are morphologically abnormal with greatly compromised motility (PubMed:23177736). Male mice display increased m6A in mRNAs in spermatocytes, leading to aberrant splicing and production of shorter transcripts that are rapidly degraded (PubMed:29279410).|||Monomer.|||Nucleus speckle|||Widely expressed, with highest expression in testis (PubMed:23177736). In testis, present in almost all testicular cell types except elongating and elongated spermatids (at protein level) (PubMed:29279410). Among spermatogenic cells, present at high level in spermatocytes; medium levels in spermatogonia and lower levels in round spermatids (at protein level) (PubMed:29279410). http://togogenome.org/gene/10090:Cox14 ^@ http://purl.uniprot.org/uniprot/Q8BH51 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Along with COA3, core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex.|||Core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. Requires for coordination of the early steps of cytochrome c oxidase assembly with the synthesis of MT-CO1.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Wipf2 ^@ http://purl.uniprot.org/uniprot/Q6PEV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the verprolin family.|||Interacts with WASL and WASP, and this interaction results in cytoplasmic relocation of these two proteins along actin filaments. Interacts with NCK2 resulting in the localization to sites of focal adhesions (By similarity).|||Plays an active role in the formation of cell surface protrusions downstream of activated PDGFB receptors. Plays an important role in actin-microspike formation through cooperation with WASL. May cooperate with WASP and WASL to induce mobilization and reorganization of the actin filament system (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Gli2 ^@ http://purl.uniprot.org/uniprot/Q0VGT2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-740 inhibits Hh target gene expression, probably by impeding entry into chromatin thus preventing promoter occupancy.|||Belongs to the GLI C2H2-type zinc-finger protein family.|||Cytoplasm|||Full embryonic lethality. Homozygous embryos are detected at the expected Mendelian rate up to about 18.5 dpc, but there are no live pups. Mutant embryos present important craniofacial defects, including defects of the medial portion of the frontal and parietal skull bones, absence of upper and/or lower incisors, often combined with a cleft palate. Besides, mutant embryos show defects in the ossification of skeletal bones and shortened limb bones.|||Functions as transcription regulator in the hedgehog (Hh) pathway (PubMed:9006072). Functions as transcriptional activator (PubMed:10806483). May also function as transcriptional repressor (PubMed:10433919). Requires STK36 for full transcriptional activator activity (PubMed:10806483). Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the TRE-2S regulatory element (By similarity). Is involved in the smoothened (SHH) signaling pathway (PubMed:10433919). Required for normal skeleton development (PubMed:9006072).|||Interacts with ZIC1 and ZIC2 (PubMed:11238441). Interacts with STK36 (PubMed:10806483). Interacts with SUFU; this inhibits transcriptional activation mediated by GLI2 (PubMed:10806483, PubMed:23034632). Interacts (via C-terminal internal region) with FOXC1 (via N-terminus); this interaction is direct and increases GLI2 DNA-binding and transcriptional activity through a smoothened (SMO)-independent Hedgehog (Hh) signaling pathway (PubMed:26565916, PubMed:25808752).|||Nucleus|||Phosphorylated in vitro by ULK3. Phosphorylated by DYRK2; this inhibits GLI2 transcription factor activity and promotes proteasomal degradation of GLI2.|||The N-terminal domain confers transcriptional repressor activity, while the C-terminal domain mediates transcriptional activation.|||cilium http://togogenome.org/gene/10090:Slc38a7 ^@ http://purl.uniprot.org/uniprot/Q8BWH0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Highly expressed in the brain, including the hippocampus, especially in the granular layer of dentate gyrus cells and the pyramidal cell layer of the hippocampus, amygdala, thalamus, hypothalamus, in the layer of Purkinje cells in the cerebellum and the layers of cortex (PubMed:21511949). Particularly strong expression in neurons of the ventromedial hypothalamus, basolateral amygdala, ventral tegmental area, and locus coeruleus (PubMed:21511949). Not detected in glial cells, including astrocytes (PubMed:21511949). In addition to brain, also expressed in the spinal cord (at protein level) (PubMed:21511949).|||Interacts with the mTORC1 complex; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation.|||Lysosome membrane|||Symporter that selectively cotransports sodium ions and amino acids, such as L-glutamine and L-asparagine from the lysosome into the cytoplasm and may participates in mTORC1 activation (PubMed:21511949, PubMed:28416685). The transport activity requires an acidic lysosomal lumen (By similarity).|||axon http://togogenome.org/gene/10090:Mcm6 ^@ http://purl.uniprot.org/uniprot/P97311|||http://purl.uniprot.org/uniprot/Q3ULG5|||http://purl.uniprot.org/uniprot/Q542I2|||http://purl.uniprot.org/uniprot/Q8C5L1 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Belongs to the MCM family.|||Chromosome|||Component of the MCM2-7 complex (PubMed:10567526). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex. May interact with MCM10. Interacts with TIPIN. Interacts with CDT1. Interacts with MCMBP. Interacts with DDI2 (By similarity).|||Component of the MCM2-7 complex.|||Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.|||Nucleus|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. http://togogenome.org/gene/10090:Gnb1l ^@ http://purl.uniprot.org/uniprot/Q9EQ15 ^@ Tissue Specificity ^@ Expressed at low levels in most tissues and highly expressed in adult testis. http://togogenome.org/gene/10090:Dmtf1 ^@ http://purl.uniprot.org/uniprot/Q8CE22 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DMTF1 family.|||Expressed throughout the cell cycle. Expression is highest in G0 and G1 phases and decreases during S and G2/M phases.|||Expression is induced by activation of the Ras-Raf signaling pathway, and this may require JUN and JUNB. Expression can be repressed by E2F1, E2F2, E2F3 and E2F4. Expression is also repressed by non-classical inhibitors of NF-kappa-B signaling such as doxorubicin, daunorubicin and UVC, and by the NF-kappa-B p65 subunit (RELA).|||Interacts with the D-type cyclins CCND1, CCND2 and CCND3. Interaction with D-type cyclins may modulate transcriptional activation by this protein.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Mice spontaneously develop tumors with a mean latency around 80 weeks. The most common tumor types are pulmonary adenomas, adenocarcinomas, hepatocellular tumors, B-cell lymphomas and vascular tumors. The protein appears to be haplo-insufficient for tumor suppression, as heterozygous animals are also prone to spontaneous tumor development. Mice lacking this protein also exhibit enhanced susceptibility to tumor induction by activated Ras or the application of dimethylbenzanthracene (DMBA) or ionizing radiation. Early passage murine embryonic fibroblasts (MEFs) from animals lacking this protein are susceptible to transformation by activated Ras alone due to functional inactivation of the ARF-p53 pathway. Late passage MEFs from animals lacking this protein escape senescence without disrupting CDKN2A/ARF or p53 function.|||Nucleus|||Phosphorylated by the cyclin-D2/CDK4, cyclin-D3/CDK4 and cyclin-D2/CDK6 complexes and to a lesser extent by the cyclin-D1/CDK4 complex.|||Transcriptional activator which activates the CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting p53/TP53-dependent growth arrest. May also cooperate with MYB to activate transcription of the ANPEP gene. Binds to the consensus sequence 5'-CCCG[GT]ATGT-3'.|||Ubiquitously expressed (at mRNA level). Expressed in brain, intestine, kidney, lung, pancreas, skin, spleen and tongue (at protein level). Expressed at high levels in testis and thymus (at protein level). In all tissues examined, expression is predominant in non-proliferating and differentiated cell types. These include epithelial, interstitial and smooth muscle cells of the intestine, differentiated spermatids, sperm and interstitial cells of the testis, and lymphoid cells of the medullary compartment of the thymus. http://togogenome.org/gene/10090:Tsc1 ^@ http://purl.uniprot.org/uniprot/Q9EP53 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the TSC-TBC complex (also named Rhebulator complex), composed of 2 molecules of TSC1, 2 molecules of TSC2 and 1 molecule of TBC1D7 (By similarity). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2 (By similarity). Forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (By similarity). Interacts (via C-terminus) with the closed form of HSP90AA1 (via the middle domain and TPR repeat-binding motif) (PubMed:29127155). Interacts with DOCK7 (By similarity). Interacts with FBXW5. Interacts with WDR45B. Interacts with RPAP3 and URI1 (By similarity).|||Conditional knockout in glia causes an increase in HSP90AA1 ATPase activity and a down-regulation of ULK1, ERBB2, ESR1 and NR3C1 protein levels in the brain.|||Lysosome membrane|||Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12820960). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12820960). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12820960). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (By similarity). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (By similarity). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (PubMed:16707451). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (By similarity). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (By similarity). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (By similarity).|||Phosphorylation at Ser-502 does not affect interaction with TSC2.|||The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.|||cytosol http://togogenome.org/gene/10090:Or4k47 ^@ http://purl.uniprot.org/uniprot/Q8VGE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Anxa3 ^@ http://purl.uniprot.org/uniprot/O35639 ^@ Domain|||Function|||Similarity ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||Inhibitor of phospholipase A2, also possesses anti-coagulant properties. http://togogenome.org/gene/10090:Fpr3 ^@ http://purl.uniprot.org/uniprot/O08790 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed exclusively in vomeronasal neurons (PubMed:19387439, PubMed:19497865). Expressed in 0.6 % of a subset of sensory neurons located in the basal layer of the vomeronasal organ. Each neuron appears to express only one receptor gene. Expressed mostly in neutrophils, followed by spleen and lung and expressed at very low levels in heart and liver (PubMed:19387439).|||Low affinity receptor for N-formyl-methionyl peptides. Receptor for lipoxin A4. May have an olfactory function associated with the identification of pathogens or of pathogenic states. http://togogenome.org/gene/10090:Hlx ^@ http://purl.uniprot.org/uniprot/Q549B7|||http://purl.uniprot.org/uniprot/Q61670|||http://purl.uniprot.org/uniprot/Q6P3B7|||http://purl.uniprot.org/uniprot/Q80YV1 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the H2.0 homeobox family.|||By TBX21 in developing as well as mature Th1 cells.|||Expressed in Th1 cells, CD8-positive T-cells, B-cells and NK cells.|||Nucleus|||Th1 cells lacking Hlx or Tbx21 fail to express normal levels of the Th1-specific cytokine Ifng.|||Transcription factor required for TBX21/T-bet-dependent maturation of Th1 cells as well as maintenance of Th1-specific gene expression. Involved in embryogenesis and hematopoiesis. http://togogenome.org/gene/10090:Srsf7 ^@ http://purl.uniprot.org/uniprot/Q8BL97 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Cytoplasm|||Extensively phosphorylated on serine residues in the RS domain.|||Found in large molecular weight complexes containing CCNL1 and the p110 isoforms of either CDC2L1 or CDC2L2 (By similarity). Interacts with CCNL2 and CPSF6. Interacts with NXF1 (By similarity). Interacts with YTHDC1 (PubMed:29799838).|||Nucleus|||Required for pre-mRNA splicing. Represses the splicing of MAPT/Tau exon 10. May function as export adapter involved in mRNA nuclear export such as of histone H2A. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway); enhances NXF1-NXT1 RNA-binding activity. RNA-binding is semi-sequence specific (By similarity). http://togogenome.org/gene/10090:Wdr82 ^@ http://purl.uniprot.org/uniprot/B2RXQ8|||http://purl.uniprot.org/uniprot/Q8BFQ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat SWD2 family.|||Chromosome|||Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (By similarity). Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC (By similarity). Associated with multiple protein complexes including an RNA polymerase II complex, MLL3/MLL4 complex and a chaperonin-containing TCP1 complex (By similarity). Interacts with CUL4B (PubMed:17041588). Interacts with RBBP5 and SETD1B (By similarity). Interacts with SETD1A (via RRM domain) (By similarity). Interacts with POLR2B (By similarity). Interacts with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) (By similarity). Binds specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each heptad (By similarity). SETD1A enhances its interaction with POLR2A (By similarity). Interacts with PPP1R10/PNUTS (By similarity). Interacts with PPP1CA in the presence of PPP1R10/PNUTS (By similarity). Interacts with ZC3H4; interaction is independent of the SET1 complex and promotes transcription termination of long non-coding RNAs (lncRNAs) (PubMed:33767452).|||Nucleus|||Regulatory component of the SET1 complex implicated in the tethering of this complex to transcriptional start sites of active genes (By similarity). Facilitates histone H3 'Lys-4' methylation (H3K4me) via recruitment of the SETD1A or SETD1B to the 'Ser-5' phosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) (By similarity). Component of PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (By similarity). Together with ZC3H4, but independently of the SET1 complex, part of a transcription termination checkpoint that promotes transcription termination of long non-coding RNAs (lncRNAs) (PubMed:33767452). The transcription termination checkpoint is activated by the inefficiently spliced first exon of lncRNAs and promotes transcription termination of lncRNAs and their subsequent degradation by the exosome (PubMed:33767452). http://togogenome.org/gene/10090:Zfp36l1 ^@ http://purl.uniprot.org/uniprot/P23950|||http://purl.uniprot.org/uniprot/Q543H2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the cytoplasmic CCR4-NOT deadenylase and RNA exosome complexes to trigger ARE-containing mRNA deadenylation and decay processes. Interacts with CNOT1. Interacts (via N-terminus) with CNOT6. Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner. Interacts with DCP1A. Interacts (via N-terminus) with DCP2. Interacts (via N-terminus) with EXOSC2. Interacts with XRN1. Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (By similarity). Interacts (via phosphorylated form) with YWHAZ; this interaction occurs in a p38 MAPK- and AKT-signaling pathways (PubMed:22701344).|||Associates with the cytoplasmic CCR4-NOT deadenylase complex to trigger ARE-containing mRNA deadenylation and decay processes.|||Cytoplasm|||Cytoplasmic granule|||Embryos die in utero at 11 dpc (PubMed:15226444, PubMed:17013884). Exhibit extraembryonic, intraembryonic, vascular and neural tube defects and cardiac abnormalities at 9.5 dpc (PubMed:17013884). Show a reduced number of circulating blood cells (PubMed:17013884). Show failure of chorioallantoic fusion (PubMed:15226444). Exhibited increased level of VEGFA protein level in embryonic fibroblasts under both normoxic and hypoxic conditions (PubMed:17013884). Knockout mice lacking both ZFP36L1 and ZFP36L2 during thymopoiesis lead to aberrant T cell development and subsequently develop a T-cell acute lymphoblastic leukemia (T-ALL) (PubMed:20622884). Show also higher levels of NOTCH1 protein and mRNA in thymocytes (PubMed:20622884). Conditional knockout mice of both ZFP36L1 and ZFP36L2 in pro-B cells display reduced B lymphocyte number and delayed variable-diversity-joining (VDJ) recombination (PubMed:27102483). Exhibit also increased protein and ARE-containing mRNA expressions of several factors implicated in cell cycle progression in late pre-B cells (PubMed:27102483).|||Expressed in embryos at 8 dpc, onward (PubMed:15226444). Expressed in the allantois and throughout the neuroectoderm and paraxial mesoderm at 8 dpc (PubMed:15226444). Expressed in the chorion and blood vessels at 8.5 dpc (PubMed:17013884). Expressed in the neural tube, paraxial mesoderm, heart, brain, otic vesicle and yolk sac at 9.5 dpc (PubMed:17013884). Expressed in embryonic stem cells (ESC) (PubMed:15226444).|||Expressed in preadipocytes and adipocytes (PubMed:22701344). Expressed in the proximal and distal tubules in the renal cortex (at protein level) (PubMed:24700863). Expressed in ovary, heart, kidney, lung, spleen and thymus (PubMed:15226444). Weakly expressed in brain, liver and testis (PubMed:15226444). Expressed in osteoblasts (PubMed:15465005). Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed through B lymphocyte development (PubMed:27102483).|||Nucleus|||P-body|||Phosphorylated (PubMed:19179481). Phosphorylated by RPS6KA1 at Ser-334 upon phorbol 12-myristate 13-acetate (PMA) treatment; this phosphorylation results in dissociation of the CCR4-NOT deadenylase complex and induces p38 MAPK-mediated stabilization of the low-density lipoprotein receptor LDLR mRNA. Phosphorylated by protein kinase AKT1 at Ser-92 and Ser-203 in response to insulin; these phosphorylations stabilize ZFP36L1, increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization. AKT1-mediated phosphorylation at Ser-92 does not impair ARE-containing RNA-binding. Phosphorylated at Ser-54, Ser-92 and Ser-203 by MAPKAPK2; these phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization in a protein kinase AKT1-independent manner. MAPKAPK2-mediated phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair ARE-containing RNA-binding (By similarity). Phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization during early adipogenesis in a p38 MAPK- and AKT-dependent manner (PubMed:22701344).|||Ubiquitinated. Ubiquitination leads to proteasomal degradation, a process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203.|||Up-regulated during myogenic differentiation in a p38 MAPK-dependent manner (PubMed:17889962). Up-regulated in response to fibroblast growth factor FGF4 in embryonic stem cells (ESCs) in a p38 MAPK-dependent manner (PubMed:24733888). Up-regulated during high sodium diet-fed in the renal tubules (PubMed:24700863). Up-regulated upon hypertonic stress condition with raffinose (at protein level) (PubMed:24700863). Up-regulated by parathyroid hormone (PTH) in calvarial osteoblasts (PubMed:15465005). Up-regulated in response to adrenocorticotropic hormone (ACTH) (PubMed:19179481). Up-regulated in response to cAMP (PubMed:19179481). Down-regulated by bone morphogenetic protein BMP2 treatment in calvarial osteoblasts (PubMed:15465005). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583).|||Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:22701344, PubMed:24700863, PubMed:24733888, PubMed:27102483). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (By similarity). Functions by recruiting the CCR4-NOT deadenylating complex and components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (By similarity). Induces also the degradation of ARE-containing mRNAs even in absence of poly(A) tail (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:22701344, PubMed:24700863, PubMed:24733888). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress (PubMed:24700863). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (By similarity). Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA (By similarity). Promotes degradation of ARE-containing pluripotency-associated mRNAs in embryonic stem cells (ESCs), such as NANOG, through a fibroblast growth factor (FGF)-induced MAPK-dependent signaling pathway, and hence attenuates ESC self-renewal and positively regulates mesendoderm differentiation (PubMed:24733888). May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA (By similarity). In association with ZFP36L2 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination and functional immune cell formation (PubMed:27102483). Together with ZFP36L2 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA (PubMed:20622884). Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (By similarity). In addition to its cytosolic mRNA-decay function, plays a role in the regulation of nuclear mRNA 3'-end processing; modulates mRNA 3'-end maturation efficiency of the DLL4 mRNA through binding with an ARE embedded in a weak noncanonical polyadenylation (poly(A)) signal in endothelial cells (By similarity). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (By similarity). Plays a role in vasculogenesis and endocardial development (PubMed:15226444, PubMed:17013884). Involved in the regulation of keratinocyte proliferation, differentiation and apoptosis (By similarity). Plays a role in myoblast cell differentiation (PubMed:17889962).|||Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes. Binds to 3'-UTR ARE of numerous mRNAs. http://togogenome.org/gene/10090:Aldh6a1 ^@ http://purl.uniprot.org/uniprot/Q8K0L1|||http://purl.uniprot.org/uniprot/Q9EQ20 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-55; Lys-117 and Lys-331 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the aldehyde dehydrogenase family.|||Homotetramer.|||Malonate and methylmalonate semialdehyde dehydrogenase involved in the catabolism of valine, thymine, and compounds catabolized by way of beta-alanine, including uracil and cytidine.|||Mitochondrion|||Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA. http://togogenome.org/gene/10090:Mras ^@ http://purl.uniprot.org/uniprot/O08989 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Forms a multiprotein complex with SHOC2, Raf (RAF1) and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts with RGL3.|||Serves as an important signal transducer for a novel upstream stimuli in controlling cell proliferation. Activates the MAP kinase pathway (By similarity). http://togogenome.org/gene/10090:Tspan6 ^@ http://purl.uniprot.org/uniprot/Q99L96 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||Membrane http://togogenome.org/gene/10090:Or9m1b ^@ http://purl.uniprot.org/uniprot/A2AVT0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Clec4g ^@ http://purl.uniprot.org/uniprot/Q8BNX1 ^@ Function|||Subcellular Location Annotation ^@ Binds mannose, N-acetylglucosamine (GlcNAc) and fucose, but not galactose, in a Ca(2+)-dependent manner.|||Cell membrane http://togogenome.org/gene/10090:Or14c39 ^@ http://purl.uniprot.org/uniprot/F8VQ84 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Capza3 ^@ http://purl.uniprot.org/uniprot/P70190 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the F-actin-capping protein alpha subunit family.|||Exclusively expressed in the testis.|||Expressed in 24-day-old and adult testis, but not in 4-, 10- and 16-day-old testis.|||F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. May play a role in the morphogenesis of spermatid.|||Heterodimer of an alpha and a beta subunit. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5 (By similarity). http://togogenome.org/gene/10090:Jph4 ^@ http://purl.uniprot.org/uniprot/Q80WT0 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the junctophilin family.|||Cell membrane|||Due to intron retention.|||Endoplasmic reticulum membrane|||Jph3 and Jph4 double null mutants exhibit atypical depolarizing responses, irregular cerebellar plasticity due to abolished crosstalk in Purkinje cells. There is hyperphosphorylation of PRKCG and mild impairment of synaptic maturation. Exploratory activity, hippocampal plasticity and memory are impaired and there is abnormal foot-clasping reflex.|||Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH4 is brain-specific and appears to have an active role in certain neurons involved in motor coordination and memory.|||Specifically expressed in brain. Highest levels in the olfactory tubercle, caudate putamen, nucleus accumbens, hippocampal formation, piriform cortex and cerebellar cortex. Expressed in disctete neurons sites. In hippocampal formation, expressed in dendrites of hippocampal pyramidal and denate granule cells. In cerebellum, it is highly expressed in Purkinje cells, while it is weakly expressed in granular cells.|||The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids. http://togogenome.org/gene/10090:Nt5dc1 ^@ http://purl.uniprot.org/uniprot/Q05AG7|||http://purl.uniprot.org/uniprot/Q8C5P5 ^@ Similarity ^@ Belongs to the 5'(3')-deoxyribonucleotidase family. http://togogenome.org/gene/10090:Nlrp9b ^@ http://purl.uniprot.org/uniprot/Q66X22 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens, including rotavirus, initiates the formation of the inflammasome polymeric complex, made of NLRP9, PYCARD and CASP1. Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and release in the extracellular milieu. The active cytokines stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. NLRP9 inflammasome activation may be initiated by DHX9 interaction with viral double-stranded RNA (dsRNA), preferentially to short dsRNA segments.|||Cytoplasm|||Down-regulated in preimplantation embryos, with decreased levels observed at the 4-cell stages. Still detectable in blastocysts (at protein level) (PubMed:15317747). Expression in oocytes decline with age. It is much higher at 10 weeks of age rather than at 40 (at protein level) (PubMed:26411641). In ileum epithelial cells, up-regulated in the first 12 hours following rotavirus infection. Levels drastically decrease 36 hours post infection (at protein level) (PubMed:28636595).|||Inflammasome|||No visible phenotype. Mutant mice exhibit normal gut homeostasis and microbiota composition. Following rotavirus infection, mutant animals have higher viral loads in the small intestine, increased fecal shedding of viral antigens, and more frequent incidences of diarrhea compared to wild-type littermates. Mice with a conditional knockout in ileum intestinal epithelial cells are also more susceptible to rotavirus infection compared to control animals.|||Predominantly expressed in the intestine, including proximal and distal colon, cecum, ileum, jejunum and duodenum (at protein level) (PubMed:26411641, PubMed:28636595). In the ileum, expressed in epithelial cells (PubMed:28636595). Also expressed in oocytes at all follicular stages and in preimplantation embryos (at protein level) (PubMed:15317747, PubMed:26411641). Although expression decreases in preimplantation embryos, it is still detectable in blastocyts (PubMed:26411641).|||Sensor component of NLRP9 inflammasomes. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens, such as rotavirus, but not encephalomyocarditis virus (EMCV), and play critical roles in innate immunity and inflammation. The core of NLRP9 inflammasomes consists of a signal sensor component (NLRP9), an adapter (ASC/PYCARD), which recruits an effector pro-inflammatory caspase (CASP1). Within the complex, NLRP9 and PYCARD interact via their respective DAPIN/pyrin domains. This interaction initiates speck formation (nucleation) which greatly enhances further addition of soluble PYCARD molecules to the speck in a prion-like polymerization process. Clustered PYCARD nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization. CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation. Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response. Interacts with DHX9 upon rotavirus infection; this interaction may trigger inflammasome activation and inflammatory response. http://togogenome.org/gene/10090:Nav2 ^@ http://purl.uniprot.org/uniprot/V9GX91|||http://purl.uniprot.org/uniprot/V9GXT3 ^@ Similarity ^@ Belongs to the Nav/unc-53 family. http://togogenome.org/gene/10090:Ifne ^@ http://purl.uniprot.org/uniprot/A0A7R8GUW5|||http://purl.uniprot.org/uniprot/Q80ZF2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha/beta interferon family.|||By estrogens. Contrary to other type I interferons, not induced by known pattern-recognition receptor pathways.|||Expressed at very high levels in uterus and, at much lower levels, in ovary and cervix. Very low levels, if any, in other organs. In the endometrium, expressed in the luminal and glandular epithelial cells (at protein level).|||Expression varies approximately 30-fold during the estrous cycle, with lowest levels during diestrus and highest at estrus. During pregnancy, uterine expression is dramatically reduced at 1.5 dpc and reaches its lowest levels at 4.5 dpc, coincident with the time of embryo implantation.|||Mutant females are substantially more susceptible to (and less able to clear) an ascending infection in the reproductive tract than wild-type animals.|||Secreted|||Type I interferon required for maintaining basal levels of IFN-regulated genes, including 2'-5'-oligoadenylate synthetase, IRF7 and ISG15, in the female reproductive tract. Directly mediates protection against viral, including HSV-2, and bacterial, including Chlamydia muridarum, genital infections. http://togogenome.org/gene/10090:Prickle3 ^@ http://purl.uniprot.org/uniprot/Q80VL3|||http://purl.uniprot.org/uniprot/Q8BNH2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the prickle / espinas / testin family.|||Cell membrane|||Cytoplasm|||Interacts with VANGL2 via its C-terminus (By similarity). The VANGL2-dependent membrane recruitment of PRICKLE3 is a prerequisite for its polarization (By similarity). Interacts with WTIP. WTIP is involved in the recruitment of PRICKLE3 to the basal body (By similarity). Interacts with MT-ATP8, a component of the mitochondrial complex V (By similarity).|||Involved in the planar cell polarity (PCP) pathway that is essential for the polarization of epithelial cells during morphogenetic processes, including gastrulation and neurulation (By similarity). PCP is maintained by two molecular modules, the global and the core modules, PRICKLE3 being part of the core module (By similarity). Distinct complexes of the core module segregate to opposite sides of the cell, where they interact with the opposite complex in the neighboring cell at or near the adherents junctions (By similarity). Involved in the organization of the basal body (By similarity). Involved in cilia growth and positioning (By similarity). Required for proper assembly, stability, and function of mitochondrial membrane ATP synthase (mitochondrial complex V) (PubMed:32516135).|||Mitochondrion|||Prickle3 knockdown results in reduced respiratory complex V activity, altered complex V assembly, and abnormal mitochondrial morphology observed in the retina. Mutant mice exhibit degeneration of retinal ganglion cells, fewer retinal neurofilaments than wild-type mice, abnormalities of the retinal vasculature, and significantly reduced retinal function.|||Widely expressed. http://togogenome.org/gene/10090:Cep162 ^@ http://purl.uniprot.org/uniprot/Q6ZQ06 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP162 family.|||Interacts with CPNE4 (PubMed:12522145). Interacts with alpha-tubulin. Interacts with CEP290 (By similarity).|||Nucleus|||Required to promote assembly of the transition zone in primary cilia. Acts by specifically recognizing and binding the axonemal microtubule. Localizes to the distal ends of centrioles before ciliogenesis and directly binds to axonemal microtubule, thereby promoting and restricting transition zone formation specifically at the cilia base. Required to mediate CEP290 association with microtubules (By similarity).|||centriole|||spindle http://togogenome.org/gene/10090:Or2y13 ^@ http://purl.uniprot.org/uniprot/Q7TQT2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Art5 ^@ http://purl.uniprot.org/uniprot/P70352|||http://purl.uniprot.org/uniprot/Q14AG6|||http://purl.uniprot.org/uniprot/Q3V0V9 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in testis. Lower levels in cardiac and skeletal muscle.|||Belongs to the Arg-specific ADP-ribosyltransferase family.|||Membrane|||Secreted http://togogenome.org/gene/10090:Sgsm3 ^@ http://purl.uniprot.org/uniprot/Q8VCZ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small G protein signaling modulator family.|||Cytoplasm|||Interacts with GJA1. Interaction with GJA1 induces its degradation. Interacts via its RUN domain with the C-terminal region of NF2. Interacts with RAB3A, RAB4A, RAB5A, RAB8A, RAB11A, RAP1A, RAP1B, RAP2A, RAP2B and PDCD6I. No interaction with RAB27A (By similarity).|||May play a cooperative role in NF2-mediated growth suppression of cells.|||Widely expressed. http://togogenome.org/gene/10090:Lce3b ^@ http://purl.uniprot.org/uniprot/Q9CQM7 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:St6galnac5 ^@ http://purl.uniprot.org/uniprot/Q6GTI0|||http://purl.uniprot.org/uniprot/Q9QYJ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||High expression in forebrain and to a lesser extent in cerebellum. No expression in salivary gland, intestine, liver, kidney, heart, lung, thymus and spleen.|||Membrane|||Predominantly catalyzes the biosynthesis of ganglioside GD1alpha from GM1b in the brain, by transferring the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of GM1b (PubMed:10601645, PubMed:10521438). GD1alpha is a critical molecule in the communication and interaction between neuronal cells and their supportive cells, particularly in brain tissues, and functions as an adhesion molecule in the process of metastasis (PubMed:9157980). Also shows activity towards sialyl Lc4Cer (N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-N-acyl-sphing-4-enine) generating disialyl Lc4Cer, which can lead to the synthesis of disialyl Lewis a (Le(a)), suggested to be a cancer-associated antigen (By similarity). http://togogenome.org/gene/10090:Amph ^@ http://purl.uniprot.org/uniprot/Q7TQF7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Heterodimer with BIN1 (By similarity). Binds SH3GLB1 (By similarity). Interacts with REPS1 and SGIP1 (By similarity). Binds AP2A2. Interacts with AP2B1. Interacts with DNM1 and SYNJ1 (By similarity).|||May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton (By similarity).|||cytoskeleton|||synaptic vesicle membrane http://togogenome.org/gene/10090:Jag2 ^@ http://purl.uniprot.org/uniprot/Q9QYE5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ At 13 dpc, found in paravertebral vessels and dorsal root ganglia. At 14 dpc, in oropharyngeal epithelium, developing thymus and in the muscles of the tongue. By 15 dpc, in many tissues.|||Found to be highest in fetal thymus, epidermis, foregut dorsal root ganglia and inner ear. In 2-weeK-old mice, abundant in heart, lung, thymus, skeletal muscle, brain and testis. Expression overlaps partially with Notch1 expression.|||Membrane|||Putative Notch ligand involved in the mediation of Notch signaling. Plays an essential role during limb, craniofacial and thymic development. May be involved in myogenesis and in the development of peripheral and central nervous systems. http://togogenome.org/gene/10090:Cnot7 ^@ http://purl.uniprot.org/uniprot/Q3TLK9|||http://purl.uniprot.org/uniprot/Q543X5|||http://purl.uniprot.org/uniprot/Q60809 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAF1 family.|||Binds 2 divalent metal cations per subunit with RNAase activity being higher in presence of Mn(2+) than of Mg(2+) or Co(2+).|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8 (By similarity). In the complex, interacts directly with CNOT1 (By similarity). Interacts with AGO2 (PubMed:19716330). Interacts with TOB1; recruited by TOB1 to a ternary complex with CPEB3 which is required for mRNA deadenylation and decay (By similarity). Interacts with BTG1 (PubMed:9712883). Interacts with BTG2 (PubMed:9712883). Interacts with NANOS2 (PubMed:20133598). Interacts with ZFP36, ZFP36L1 and ZFP36L2; these interactions are inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (By similarity). Interacts with BTG4 (PubMed:27065194). Interacts with EIF4E; this interaction is increased by CNOT7 interaction with BTG4 (PubMed:27065194).|||Cytoplasmic ribonucleoprotein granule|||Expressed in embryonic stem (ES) cells.|||Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT8. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for miRNA-mediated mRNA deadenylation. Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity.|||Nucleus|||P-body http://togogenome.org/gene/10090:Celsr3 ^@ http://purl.uniprot.org/uniprot/Q91ZI0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Cell membrane|||Expressed in the CNS and in the eye.|||Predominantly expressed in the CNS, the emerging dorsal root ganglia and cranial ganglia. In the CNS, expression is uniform along the rostrocaudal axis. No expression is detected until somite stages. Between 10 and 12 dpc, expression is strong in the marginal zone (MZ), and lower in the ventricular zone (VZ). At 15 dpc, expression is restricted to the brain and olfactory epithelium. In the brain, it is low in VZ but strong in external fields, particularly those with ongoing migration, such as the telencephalic cortical plate, the olfactory bulb, the cerebellum and the tectum. In the newborn and postnatal stages, expression is high in differentiated neuronal fields.|||Receptor that may have an important role in cell/cell signaling during nervous system formation. http://togogenome.org/gene/10090:Pias3 ^@ http://purl.uniprot.org/uniprot/O54714 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIAS family.|||Cytoplasm|||Expressed as early as 7.6 dpc. Expression remains high through 15.5 dpc.|||Expressed in kidney, heart, spleen, brain and cerebellum; weak expression, if any, in liver and lung.|||Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway. Repressor of STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Repressor of MITF transcriptional activity. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. Sumoylates CCAR2 which promotes its interaction with SIRT1 (By similarity). Diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus (By similarity).|||Monomer. Interacts with PLAG1 and ZFHX3. Interacts with STAT5A; the interaction occurs on stimulation by PRL (By similarity). Binds SUMO1 and UBE2I. Interacts with AR, BCL11A, HMGA2, IRF1 and NCOA2. Interacts with MITF; the interaction inhibits the transcriptional activity of MITF. Interacts with STAT3; the interaction occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. Interacts with GFI1; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. Interacts with MTA1. Interacts with CCAR2 (via N-terminus) (By similarity). Interacts with TRIM8 (By similarity). Interacts with PRDM1 (By similarity).|||Nucleus|||Nucleus speckle|||Sumoylated.|||The LXXLL motif is a transcriptional coregulator signature. http://togogenome.org/gene/10090:Gria1 ^@ http://purl.uniprot.org/uniprot/F6YNQ1|||http://purl.uniprot.org/uniprot/P23818|||http://purl.uniprot.org/uniprot/Q7TNB5 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA1 subfamily.|||Cell membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Expressed in the outer plexiform layer of the retina of the eye (at protein level) (PubMed:28334377). Expressed in the forebrain and hippocampus (at protein level) (PubMed:31651360).|||Homotetramer or heterotetramer of pore-forming glutamate receptor subunits (By similarity). Tetramers may be formed by the dimerization of dimers (By similarity). Found in a complex with GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity). Interacts with HIP1 and RASGRF2 (PubMed:12839988, PubMed:16407208). Interacts with SYNDIG1 and GRIA2 (PubMed:20152115). Interacts with DLG1 (via C-terminus). Interacts with LRFN1. Interacts with PRKG2. Interacts with CNIH2 and CACNG2. Interacts with CACNG5. Interacts (via C-terminus) with PDLIM4 (via LIM domain); this interaction as well as the interaction of PDLIM4 with alpha-actinin is required for their colocalization in early endosomes. Found in a complex with GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:23524343). Interacts (via PDZ-binding motif) with SHANK3 (via PDZ domain) (PubMed:16606358). Interacts with CACNG3; associates GRIA1 with the adapter protein complex 4 (AP-4) to target GRIA1 to the somatodendritic compartment of neurons (PubMed:18341993).|||Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.|||Membrane|||Palmitoylated. Depalmitoylated upon glutamate stimulation. ZDHHC3/GODZ specifically palmitoylates Cys-603, which leads to Golgi retention and decreased cell surface expression. In contrast, Cys-829 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis.|||Phosphorylated at Ser-645. Phosphorylated at Ser-710 by PKC. Phosphorylated at Ser-849 by PKC, PKA and CAMK2. Phosphorylated at Ser-863 by PKC, PKA and PRKG2 (By similarity). Phosphorylation of Ser-863 is reduced by induction of long-term depression and increased by induction of long-term potentiation (PubMed:23676497).|||Postsynaptic cell membrane|||Postsynaptic density membrane|||Presynapse|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.|||Recycling endosome membrane|||Synapse|||The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.|||The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Gstcd ^@ http://purl.uniprot.org/uniprot/Q5RL51 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the GSTCD family.|||Cytoplasm http://togogenome.org/gene/10090:Bcl2l14 ^@ http://purl.uniprot.org/uniprot/Q9CPT0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Bcl-2 family.|||Cytoplasm|||Phosphorylated by MELK, leading to inhibit its pro-apoptotic function.|||Plays a role in apoptosis. http://togogenome.org/gene/10090:Eno3 ^@ http://purl.uniprot.org/uniprot/P21550 ^@ Cofactor|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the enolase family.|||Brain (at protein level). The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons. In striated muscle, the fiber-type order of ENO3 expression is IIB > IIX > IIA > I.|||Cytoplasm|||During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells, and to the alpha/gamma heterodimer in nerve cells. In hindleg muscle, first expressed at 15 dpc after which, levels increase sharply between 15 dpc and 17 dpc. A steep prenatal rise in expression accompanies the formation of secondary myofibers and the development of innervation. High levels continue throughout newborn and adult stages. Beginning at postnatal day 5, a second sharp increase in expression correlates with the definitive specialization of the myofibers. Later in development, mainly expressed in fast-twitch fibers. In cardiac muscle, first expressed in the embryo in the cardiac tube.|||Glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Appears to have a function in striated muscle development and regeneration.|||Levels decrease in degenerating myofibers, and increase with their regeneration.|||Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific. In vitro, interacts with several glycolytic enzymes including PKM, PGM, CKM and ALDO. Also binds PLG and troponin, in vitro. Interacts with PNKD (By similarity).|||Mg(2+) is required for catalysis and for stabilizing the dimer. http://togogenome.org/gene/10090:Mks1 ^@ http://purl.uniprot.org/uniprot/Q284W0|||http://purl.uniprot.org/uniprot/Q5SW45 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Involved in centrosome migration to the apical cell surface during early ciliogenesis. Required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. Required for cell branching morphology.|||Part of the tectonic-like complex (also named B9 complex) (PubMed:22179047, PubMed:21725307). Interacts with TMEM107 (By similarity). Interacts with TCTN3, AHI1, TCTN1, TCTN2, CC2D2A (PubMed:21565611). Interacts with FLNA. Interacts with TMEM67 (By similarity). Interacts with B9D1 and B9D2 (PubMed:21763481, PubMed:21565611).|||Widely expressed in embryo at 15.5 dpc, with a relatively strong expression in brain, liver, kidney and digits of the upper limbs. Highly expressed in bronchiolar epithelium.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Gcnt2 ^@ http://purl.uniprot.org/uniprot/P97402|||http://purl.uniprot.org/uniprot/Q6T5E4|||http://purl.uniprot.org/uniprot/Q7TPQ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 14 family.|||Branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans. Introduces the blood group I antigen during embryonic development. It is closely associated with the development and maturation of erythroid cells.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Cd248 ^@ http://purl.uniprot.org/uniprot/Q91V98 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected at 19 dpc in embryo.|||Expressed in cell lines derived from endothelial cells, embryonic fibroblasts and preadipocytes.|||May be N-glycosylated.|||May play a role in angiogenesis or vascular function.|||Membrane|||O-glycosylated by sialylated oligosaccharides. http://togogenome.org/gene/10090:Vrtn ^@ http://purl.uniprot.org/uniprot/Q3SYK4 ^@ Similarity ^@ Belongs to the vertnin family. http://togogenome.org/gene/10090:Tap1 ^@ http://purl.uniprot.org/uniprot/P21958|||http://purl.uniprot.org/uniprot/Q3TBA3|||http://purl.uniprot.org/uniprot/Q3U6V4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ABC transporter associated with antigen processing. In complex with TAP2 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. During the transport cycle alternates between 'inward-facing' state with peptide binding site facing the cytosol to 'outward-facing' state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent 'outward-facing' conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the 'inward facing' state for a new cycle. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.|||Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.|||Endoplasmic reticulum membrane|||Heterodimer of TAP1 and TAP2 (TAP1-TAP2). A component of the peptide loading complex (PLC), interacts via TAPBP with MHCI heterodimer; this interaction mediates peptide-MHCI assembly. Interacts with PSMB5 and PSMB8.|||Membrane|||The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis.|||The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2. http://togogenome.org/gene/10090:Fasl ^@ http://purl.uniprot.org/uniprot/P41047|||http://purl.uniprot.org/uniprot/Q544E9|||http://purl.uniprot.org/uniprot/Q99PH8 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A deficiency in this protein is the cause of generalized lymphoproliferation disease phenotype (gld). Gld mice present lymphadenopathy and autoantibody production. The phenotype is recessively inherited.|||Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:7511063). Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:19794494, PubMed:7532682). Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (PubMed:19794494). TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (PubMed:10779162). Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (By similarity).|||Cytoplasmic form induces gene transcription inhibition.|||Cytoplasmic vesicle lumen|||Expressed in T-cells (PubMed:19794494). Expressed in natural killer cells (PubMed:7532682).|||Homotrimer. Interacts with ARHGAP9, BAIAP2L1, BTK, CACNB3, CACNB4, CRK, DLG2, DNMBP, DOCK4, EPS8L3, FGR, FYB1, FYN, HCK, ITK, ITSN2, KALRN, LYN, MACC1, MIA, MPP4, MYO15A, NCF1, NCK1, NCK2, NCKIPSD, OSTF1, PIK3R1, PSTPIP1, RIMBP3C, SAMSN1, SH3GL3, SH3PXD2B, SH3PXD2A, SH3RF2, SKAP2, SNX33, SNX9, SORBS3, SPTA1, SRC, SRGAP1, SRGAP2, SRGAP3, TEC, TJP3 and YES1.|||Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways (PubMed:19794494). Can induce apoptosis but does not appear to be essential for this process (By similarity).|||Lysosome lumen|||Monoubiquitinated.|||N-glycosylated. Glycosylation enhances apoptotic activity.|||Nucleus|||Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization.|||Secreted|||The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form undergoes two successive intramembrane proteolytic cleavages. The first one is processed by ADAM10 producing an N-terminal fragment, which lacks the receptor-binding extracellular domain. This ADAM10-processed FasL (FAsL APL) remnant form is still membrane anchored and further processed by SPPL2A that liberates the FasL intracellular domain (FasL ICD). FasL shedding by ADAM10 is a prerequisite for subsequent intramembrane cleavage by SPPL2A in T-cells. http://togogenome.org/gene/10090:Nol11 ^@ http://purl.uniprot.org/uniprot/Q8BJW5 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Interacts with UTP4. Interacts with FBL/fibrillarin in a transcription-dependent manner. May associate with the proposed t-UTP subcomplex of the SSU processome containing at least UTP4, WDR43, HEATR1, UTP15, WDR75.|||May be due to a competing acceptor splice site.|||Ribosome biogenesis factor. May be required for both optimal rDNA transcription and small subunit (SSU) pre-rRNA processing at sites A', A0, 1 and 2b (By similarity).|||nucleolus http://togogenome.org/gene/10090:Nphp4 ^@ http://purl.uniprot.org/uniprot/P59240 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NPHP4 family.|||Expressed in the retina (at protein level).|||Interacts with NPHP1 and RPGRIP1L/NPHP8; NPHP1, NPHP4 and RPGRIP1L are proposed to form a functional NPHP1-4-8 module localized to cell-cell contacts and the ciliary transition zone; NPHP4 mediates the interaction between NPHP1 and RPGRIP1L. Interacts with IQCB1/NPHP5; the interaction likely requires additional interactors (PubMed:21565611). Interacts with RPGRIP1, CEP164, JADE1, PALS1, INADL, PARD6A, INVS, DVL2. Interacts with INTU; INTU mediates the interaction between NPHP4 and DAAM1. Interacts with JADE1 (By similarity). Interacts with SPATA7 (PubMed:29899041).|||Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module. Does not seem to be strictly required for ciliogenesis (By similarity). Required for building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells. Seems to recruit INT to basal bodies of motile cilia which subsequently interacts with actin-modifying proteins such as DAAM1 (By similarity). In cooperation with INVS may down-regulate the canonical Wnt pathway and promote the Wnt-PCP pathway by regulating expression and subcellular location of disheveled proteins. Stabilizes protein levels of JADE1 and promotes its translocation to the nucleus leading to cooperative inhibition of canonical Wnt signaling (By similarity). Acts as negative regulator of the hippo pathway by association with LATS1 and modifying LATS1-dependent phosphorylation and localization of WWTR1/TAZ (By similarity).|||centrosome|||cilium basal body|||tight junction http://togogenome.org/gene/10090:Vrk3 ^@ http://purl.uniprot.org/uniprot/Q8K3G5 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.|||Expressed in liver, kidney, muscle, thymus, and bone marrow. Weakly expressed in spleen.|||Inactive as a kinase due to its inability to bind ATP.|||Inactive kinase that suppresses ERK activity by promoting phosphatase activity of DUSP3 which specifically dephosphorylates and inactivates ERK in the nucleus.|||Interacts with DUSP3. Interacts with RAN (By similarity).|||Nucleus|||Weakly expressed in embryo compared to VRK1 and VRK3. Expressed from 10.5 dpc to 13.5 dpc in developing liver and then decreases. It increases again from 17.5 dpc and remains thereafter. Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to 14.5 dpc. Strongly expressed in the yolk-sac. http://togogenome.org/gene/10090:Rab11fip3 ^@ http://purl.uniprot.org/uniprot/Q8CHD8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cleavage furrow|||Downstream effector molecule for Rab11 GTPase which acts as a regulator of endocytic trafficking and intracellular ciliogenesis by participating in membrane delivery (PubMed:18685082). Recruited by Rab11 to endosomes where it links Rab11 to dynein motor complex. The functional Rab11-RAB11FIP3-dynein complex then regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endocytic recycling compartment (ERC) during interphase of cell cycle. Facilitates the interaction between dynein and dynactin and activates dynein processivity (By similarity). Binding with ASAP1 is also needed to regulates the pericentrosomal localization of recycling endosomes (PubMed:18685082). The Rab11-RAB11FIP3 complex is also implicated in the transport and fusion of vesicles derived from recycling endosomes to the cleavage furrow during late cytokinesis and abscission. Also regulates cleavage furrow ingression and abscission together with RACGAP1. Required for ARF6 recruitment to the cleavage furrow during cytokinesis. Involved in the Rab11-Rabin8-Rab8 ciliogenesis cascade by facilitating the orderly assembly of a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which direct preciliary vesicle trafficking to mother centriole and ciliogenesis initiation. Also promotes the activity of Rab11 and ASAP1 in the ARF4-dependent Golgi-to-cilia transport of the sensory receptor rhodopsin. Competes with WDR44 for binding to Rab11, which controls intracellular ciliogenesis pathway. May play a role in breast cancer cell motility by regulating actin cytoskeleton (By similarity).|||Golgi apparatus membrane|||Homodimer. Interacts with RAB11A; the interaction is direct and is required for the recruitment to endosomes. Interacts with RAB11B. Forms a ternary complex with RAB11A and dynein intermediate chain DYNC1LI1; RAB11FIP3 links RAB11A to dynein and the interaction regulates endocytic trafficking. Interacts with dynein intermediate chain and dynactin (DCTN1); the interaction activates dynein processivity. Forms a complex with Rab11 (RAB11A or RAB11B) and ARF6. Interacts with RACGAP1/MgcRacGAP; interaction takes place during late stage of cytokinesis and is required for recruitment to the midbody. Forms a complex with RAB11A and Rabin8/RAB3IP, probably a heterohexamer with two of each protein subunit, where RAB3IP and RAB11FIP3 simultaneously bind to RAB11A; the complex promotes preciliary trafficking (By similarity). Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport (PubMed:18685082). Interacts with EXOC7. Interacts with RAB11FIP4. Interacts with RAB25 (By similarity).|||Midbody|||Recycling endosome membrane|||The RBD-FIP domain mediates the interaction with Rab11 (RAB11A or RAB11B).|||centrosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Hgsnat ^@ http://purl.uniprot.org/uniprot/Q3UDW8 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A signal sequence is predicted but has been shown not to be cleaved in the reticulum endoplasmic.|||Expressed in the developing eye as early as 14 dpc, with equal high expression levels after birth (postnatal day 1 (P1) and postnatal day 30 (P30)).|||Expressed in the retina.|||Glycosylated.|||Homooligomer. Homooligomerization is necessary for enzyme activity (By similarity).|||Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase.|||Lysosome membrane|||Undergoes intralysosomal proteolytic cleavage; occurs within the end of the first and/or the beginning of the second luminal domain and is essential for the activation of the enzyme. http://togogenome.org/gene/10090:Dnajb12 ^@ http://purl.uniprot.org/uniprot/Q9QYI4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway. Acts by determining HSPA8/Hsc70's ATPase and polypeptide-binding activities. Can also act independently of HSPA8/Hsc70: together with DNAJB14, acts as a chaperone that promotes maturation of potassium channels KCND2 and KCNH2 by stabilizing nascent channel subunits and assembling them into tetramers. While stabilization of nascent channel proteins is dependent on HSPA8/Hsc70, the process of oligomerization of channel subunits is independent of HSPA8/Hsc70. When overexpressed, forms membranous structures together with DNAJB14 and HSPA8/Hsc70 within the nucleus; the role of these structures, named DJANGOs, is still unclear.|||Belongs to the DnaJ family. DNAJB12/DNAJB14 subfamily.|||Endoplasmic reticulum membrane|||Homodimer and homotetramer. Interacts (via J domain) with HSPA8/Hsc70. Forms a multiprotein complex, at least composed of DNAJB12, DNAJB14, HSPA8/Hsc70 and SGTA; interaction with DNAJB14 and HSPA8/Hsc70 is direct.|||Methylated at His-186 by METTL9.|||Nucleus membrane http://togogenome.org/gene/10090:Dync1h1 ^@ http://purl.uniprot.org/uniprot/Q9JHU4 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynein heavy chain family.|||Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression.|||Defects in Dync1h1 are the cause of the 'Legs at odd angles' (LOA) phenotype, an autosomal dominant trait where affected animals display unusual twisting of the body and clenching of the hindlimbs when suspended by the tail. Heterozygotes suffer age-related progressive loss of muscle tone and locomotor ability without major reduction in life-span while homozygotes show a more severe phenotype with an inability to move or feed, and die within 24 hours of birth. LOA mutants display defects in migration of facial motor neuron cell bodies and impaired retrograde transport in spinal cord motor neurons.|||Defects in Dync1h1 are the cause of the Cramping 1 (Cra1) phenotype, an autosomal dominant trait where affected animals display unusual twisting of the body and clenching of the hindlimbs when suspended by the tail. Heterozygotes suffer age-related progressive loss of muscle tone and locomotor ability without major reduction in life-span while homozygotes show a more severe phenotype with an inability to move or feed, and die within 24 hours of birth.|||Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.|||Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and dynein LCs assemble on the IC dimer. Interacts with DYNC1LI1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with DYNC1LI2; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with DYNC1I2 (By similarity). Interacts with BICD2 (PubMed:22956769). Interacts with DNALI1 (PubMed:16496424).|||cytoskeleton http://togogenome.org/gene/10090:Scarf1 ^@ http://purl.uniprot.org/uniprot/Q5ND28|||http://purl.uniprot.org/uniprot/Q68EF1 ^@ Caution|||Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed strongly in brain, spinal cord and dorsal root ganglions at 18 dpc.|||Expressed weakly in brain, spinal cord and dorsal root ganglions.|||Heterophilic interaction with SREC2 via its extracellular domain. The heterophilic interaction is suppressed by the presence of ligand such as Ac-LDL (By similarity). Interacts with AVIL; the interaction occurs in embryonic dorsal root ganglions at 18 dpc and induces neurite-like outgrowth.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). Mediates heterophilic interactions, suggesting a function as adhesion protein (By similarity). Plays a role in the regulation of neurite-like outgrowth.|||Membrane|||The cytoplasmic domain is necessary for the regulation of neurite-like outgrowth. http://togogenome.org/gene/10090:Rbp1 ^@ http://purl.uniprot.org/uniprot/Q00915|||http://purl.uniprot.org/uniprot/Q58EU7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Cytoplasmic retinol-binding protein. Accepts retinol from the transport protein STRA6, and thereby contributes to retinol uptake, storage and retinoid homeostasis.|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Interacts (only as retinol-free apoprotein) with STRA6.|||Lipid droplet|||No visible phenotype when mice are kept on a vitamin A-enriched diet. Still, mutant mice have impaired vitamin A homeostasis. Four week old mice have reduced levels of retinoids in the liver, due to more rapid vitamin A turnover. When mice are kept on a vitamin A-deficient diet after weaning, they gain weight normally during the first 5 weeks, and then stop gaining weight. Their hepatic retinyl palmitate stores begin to decrease from the moment they are fed a vitamin A-deficient diet and become undetectable after 14 weeks, After this, serum retinol levels decrease rapidly and approach undetectable levels after 24 weeks on a vitamin A-deficient diet. After 23 weeks on a vitamin A-deficient diet, electroretinograms show dramatically decreased amplitudes of the a and b waves in response to light. At the same time, their eyes show impaired contact between the retinal pigment epithelium and the outer segment photoreceptors. Knockout mice exhibit memory deficits (PubMed:26030625). http://togogenome.org/gene/10090:Hacd2 ^@ http://purl.uniprot.org/uniprot/Q9D3B1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the very long-chain fatty acids dehydratase HACD family.|||Catalyzes the third of the very long-chain fatty acids (VLCFA) elongation four-step cycle (condensation, reduction, dehydration, and reduction). This endoplasmic reticulum-elongation process is characterized by the addition of two carbons to the lipid chain through each cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of elongation. Therefore, it participates in the production of various VLCFAs involved in multiple biological processes as precursors of membrane lipids and lipid mediators.|||Endoplasmic reticulum membrane|||May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex. Interacts with BCAP31.|||Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity. http://togogenome.org/gene/10090:Kif11 ^@ http://purl.uniprot.org/uniprot/Q6P9P6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. BimC subfamily.|||Cytoplasm|||Interacts with the thyroid hormone receptor in the presence of thyroid hormone. Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5. Interacts with RARRES1 and AGBL2 (By similarity).|||Motor protein required for establishing a bipolar spindle during mitosis. Required in non-mitotic cells for transport of secretory proteins from the Golgi complex to the cell surface.|||Phosphorylated exclusively on serine during S phase, but on both serine and Thr-925 during mitosis, so controlling the association of KIF11 with the spindle apparatus (probably during early prophase).|||spindle pole http://togogenome.org/gene/10090:Vmn2r77 ^@ http://purl.uniprot.org/uniprot/L7N2B7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Itga10 ^@ http://purl.uniprot.org/uniprot/E9PXZ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the integrin alpha chain family.|||Membrane http://togogenome.org/gene/10090:Fgf6 ^@ http://purl.uniprot.org/uniprot/A0A7U3L4H7|||http://purl.uniprot.org/uniprot/P21658|||http://purl.uniprot.org/uniprot/Q8C399 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Embryos, adult muscles and adult testis.|||Interacts with FGFR1, FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Plays an important role in the regulation of cell proliferation, cell differentiation, angiogenesis and myogenesis, and is required for normal muscle regeneration.|||extracellular space http://togogenome.org/gene/10090:Tex38 ^@ http://purl.uniprot.org/uniprot/A2A8T7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fancc ^@ http://purl.uniprot.org/uniprot/E9QAE8|||http://purl.uniprot.org/uniprot/P50652|||http://purl.uniprot.org/uniprot/Q8CBR3 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aberrant splicing.|||Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. This complex may also include HSP70.|||Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. This complex may also include HSP70. Interacts with ZBTB32. Upon IFNG induction, interacts with STAT1. Interacts with CDK1. Interacts with EIF2AK2 (By similarity).|||Cytoplasm|||DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1 (By similarity).|||DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1.|||Embryos from days 8-13 show a uniform pattern of expression with somewhat higher level expression in days 8 and 9 in the head mesenchyme as compared to the rest of the embryo. Higher levels of expression are seen in the developing bones of 14 to 16 day embryos. In the 15 day embryo it is detected in the perichondrium and the marrow of the iliac bone and perichondrium of the ribs and vertebrae. In the 16 day embryo it is detected in the perichondrial layer of the developing digits of the forelimb, outer root sheath of the hair follicles of the upper jaw and in the perichondrium of the vertebrae.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Or11h4 ^@ http://purl.uniprot.org/uniprot/E9Q438 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcif1 ^@ http://purl.uniprot.org/uniprot/P59114 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAPAM family.|||Cap-specific adenosine methyltransferase activity is inhibited by zinc.|||Cap-specific adenosine methyltransferase that catalyzes formation of N(6),2'-O-dimethyladenosine cap (m6A(m)) by methylating the adenosine at the second transcribed position of capped mRNAs (PubMed:30487554). Recruited to the early elongation complex of RNA polymerase II (RNAPII) via interaction with POLR2A and mediates formation of m6A(m) co-transcriptionally (By similarity).|||Interacts with POLR2A; interacts with the phosphorylated C-terminal domain (CTD) of POLR2A.|||Nucleus|||The WW domain is sufficient for direct and specific interaction with the phosphorylated CTD of RNAPII largest subunit. http://togogenome.org/gene/10090:Myod1 ^@ http://purl.uniprot.org/uniprot/P10085 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylated by a complex containing EP300 and PCAF. The acetylation is essential to activate target genes. Conversely, its deacetylation by SIRT1 inhibits its function.|||Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation (PubMed:16901893). Together with MYF5 and MYOG, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Interacts with and is inhibited by the twist protein. This interaction probably involves the basic domains of both proteins (PubMed:21798092, PubMed:3175662).|||Interacts with SUV39H1 (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Seems to form active heterodimers with ITF-2. Interacts with DDX5. Interacts with CHD2. Interacts with TSC22D3 isoform 1 and isoform 4. Interacts with SETD3 (PubMed:21832073). Interacts with P-TEFB complex; promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation (PubMed:12037670). Interacts with CSRP3 (By similarity). Interacts with NUPR1 (PubMed:19723804).|||Methylation at Lys-104 by EHMT2/G9a inhibits myogenic activity.|||Nucleus|||Phosphorylated by CDK9. This phosphorylation promotes its function in muscle differentiation (By similarity).|||Ubiquitinated on the N-terminus; which is required for proteasomal degradation. http://togogenome.org/gene/10090:Gm20801 ^@ http://purl.uniprot.org/uniprot/Q5FWB5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or8k21 ^@ http://purl.uniprot.org/uniprot/L7MU59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Avpr2 ^@ http://purl.uniprot.org/uniprot/O88721|||http://purl.uniprot.org/uniprot/Q3KNZ4|||http://purl.uniprot.org/uniprot/Q3SWS1|||http://purl.uniprot.org/uniprot/Q3SWS4 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.|||Cell membrane|||Highly expressed in kidney (at protein level) and moderately expressed in liver (at protein level). No or extremely low expression in left ventricule, muscle, bone and brain (at protein level).|||Interacts with ARRDC4 (By similarity). Identified in a complex containing at least ARRDC4, V2R and HGS (By similarity). Interacts with TMEM147 (By similarity).|||Involved in renal water reabsorption. Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption (By similarity). http://togogenome.org/gene/10090:Defb12 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0S5|||http://purl.uniprot.org/uniprot/Q8K4N3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Only expressed in epididymis (caput, corpus and cauda).|||Secreted http://togogenome.org/gene/10090:Rnf215 ^@ http://purl.uniprot.org/uniprot/Q5SPX3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pgap4 ^@ http://purl.uniprot.org/uniprot/Q91YV9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PGAP4 family.|||Contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold. Transmembrane domain 1 functions as a signal for Golgi targeting.|||Golgi apparatus membrane|||Golgi-resident glycosylphosphatidylinositol (GPI)-N-acetylgalactosamine transferase involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchors proteins. Required for the initial step of GPI-GalNAc biosynthesis, transfers GalNAc to GPI in the Golgi after fatty acid remodeling by PGAP2.|||The conserved DXD motif is involved in enzyme activity. http://togogenome.org/gene/10090:Supt7l ^@ http://purl.uniprot.org/uniprot/Q9CZV5 ^@ PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, SUPT7L, GCN5L2, TAF5L, TAF6L, TADA3L, TAD1L, TAF10, TAF12 and TAF9.|||Nucleus|||Sumoylated. http://togogenome.org/gene/10090:Il18 ^@ http://purl.uniprot.org/uniprot/P70380|||http://purl.uniprot.org/uniprot/Q2PMY2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-1 family.|||Cytoplasm|||Forms a ternary complex with ligand-binding receptor subunit IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane. Mature IL18 first binds to IL18R1 forming a low affinity binary complex, which then interacts with IL18RAP to form a high affinity ternary complex that signals inside the cell. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:26638072, PubMed:26638073). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (By similarity). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (By similarity). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:30392956).|||Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses. Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells. Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore.|||Secreted|||The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form. http://togogenome.org/gene/10090:Cklf ^@ http://purl.uniprot.org/uniprot/Q9DAS1 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the chemokine-like factor family.|||Intron retention.|||May play an important role in inflammation and regeneration of skeletal muscle (By similarity). Essential for embryonic development (PubMed:34446558).|||Membrane|||Mice exhibit embryonic lethality.|||Ubiquitous. http://togogenome.org/gene/10090:Dtwd1 ^@ http://purl.uniprot.org/uniprot/Q9D8U7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TDD superfamily. DTWD1 family.|||Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20 in the D-loop of several cytoplasmic tRNAs (acp3U(20)).|||Nucleus http://togogenome.org/gene/10090:Vmn1r202 ^@ http://purl.uniprot.org/uniprot/Q8R259 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Unc45b ^@ http://purl.uniprot.org/uniprot/Q8CGY6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A band|||Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain. Plays a role in sarcomere formation during muscle cell development (PubMed:12356907, PubMed:18326487, PubMed:18478096). Is necessary for normal early lens development (By similarity).|||Detected in fusing myoblasts during muscle cell differentiation. Highly expressed in young myotubes that are in the process of assembling and remodeling myofibrils. Subsequently, levels decrease during myotube maturation.|||Highly expressed in adult skeletal muscle and heart. Detected at intermediate levels in lung. Highly expressed in embryonic heart.|||Interacts with HSP90 in an ATP-independent manner (PubMed:18326487, PubMed:18478096). Interacts with UBE4B; the interaction may target UNC45B for proteasomal degradation (By similarity).|||Z line|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Dhcr7 ^@ http://purl.uniprot.org/uniprot/A0A140LIT2|||http://purl.uniprot.org/uniprot/O88455 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 7-dehydrocholesterol reductase of the cholesterol biosynthetic pathway reducing the C7-C8 double bond of cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol/7-DHC) and cholesta-5,7,24-trien-3beta-ol, two intermediates in that pathway.|||Belongs to the ERG4/ERG24 family.|||Deficient mice die within one day of birth due to respiratory and suckling problems. They exhibit abnormal cholesterol homeostasis with reduced tissue cholesterol levels and total sterol levels, enlarged bladders and sometimes cleft palate.|||Endoplasmic reticulum membrane|||Interacts with DHCR24; this interaction regulates DHCR7 activity. Interacts with TMEM147.|||Membrane http://togogenome.org/gene/10090:Or5an11 ^@ http://purl.uniprot.org/uniprot/E9Q9Z6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or8s16 ^@ http://purl.uniprot.org/uniprot/Q7TS17 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Oas1d ^@ http://purl.uniprot.org/uniprot/Q3UXA2|||http://purl.uniprot.org/uniprot/Q8VI95 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 2-5A synthase family.|||Cytoplasm|||Detected in fully grown, germinal vesicle (GV)-intact oocytes and in oocytes at the metaphase II stage, with levels decreasing thereafter (at protein level) (PubMed:15899864). Detected 1 week after birth in developing ovary (PubMed:27663720). Detected at 17.5 dpc, with levels increasing thereafter (PubMed:17567914).|||Does not have 2'-5'-olygoadenylate synthetase activity, but can bind double-stranded RNA (PubMed:15899864, PubMed:12396720). May play a role in the control of female fertility, possibly by binding to and inhibiting OAS1A (PubMed:15899864).|||Expressed specifically in oocytes (at protein level) (PubMed:15899864). Expressed at highest level in ovary with lesser amounts in intestine, brain, thymus lung, kidney, liver and uterus (PubMed:17567914, PubMed:27663720).|||Interacts with OAS1A, the interaction inhibits OAS1A catalytic activity.|||Newborn mice are viable. Female mice display reduced fertility due to deficiencies in ovarian follicle development, reduced efficiency of ovulation, and the arrest of fertilized eggs at one-cell stage.|||Unlike other OAS1 proteins, not induced by polyinosinic:polycytidylic acid (poly I:C). http://togogenome.org/gene/10090:Fgl1 ^@ http://purl.uniprot.org/uniprot/Q71KU9 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Blockade of the FGL1-LAG-3 interaction using a monoclonal antibody stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand interdependent manner.|||Homodimer (By similarity). Interacts (via the Fibrinogen C-terminal domain) with LAG3 (via Ig-like domains 1 and 2) (PubMed:30580966).|||Immune suppressive molecule that inhibits antigen-specific T-cell activation by acting as a major ligand of LAG3 (PubMed:30580966). Responsible for LAG3 T-cell inhibitory function (PubMed:30580966). Binds LAG3 independently from MHC class II (MHC-II) (PubMed:30580966). Secreted by, and promotes growth of, hepatocytes (By similarity).|||Mainly expressed in liver (PubMed:12528893, PubMed:23483972). Also expressed in brown adipose tissue (PubMed:23483972).|||Mice develop normally but develop spontaneous autoimmune symptoms caused by T-cell activation in aged mice (PubMed:30580966). Mice also display slight metabolic defects: mice are heavier than wild type mates, have abnormal plasma lipid profiles, fasting hyperglycemia with enhanced gluconeogenesis and exhibit differences in white and brown adipose tissue morphology (PubMed:23483972).|||Secreted http://togogenome.org/gene/10090:Trappc1 ^@ http://purl.uniprot.org/uniprot/Q14BF8|||http://purl.uniprot.org/uniprot/Q5NCF2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAPP small subunits family.|||Belongs to the TRAPP small subunits family. BET5 subfamily.|||Endoplasmic reticulum|||May play a role in vesicular transport from endoplasmic reticulum to Golgi.|||Part of the multisubunit transport protein particle (TRAPP) complex.|||Part of the multisubunit transport protein particle (TRAPP) complex. The heterodimer TRAPPC6B-TRAPPC3 interacts with TRAPPC1 likely providing a core for TRAPP complex formation.|||cis-Golgi network http://togogenome.org/gene/10090:Ube2f ^@ http://purl.uniprot.org/uniprot/Q9CY34 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX2, but not RBX1, suggests that the RBX2-UBE2F complex neddylates specific target proteins, such as CUL5.|||Belongs to the ubiquitin-conjugating enzyme family. UBE2F subfamily.|||Interacts with UBA3 and RBX2. Interacts (N-terminally acetylated form) with (via DCUN1 domain) DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (By similarity).|||The acetylation of Met-1 increases affinity for DCUN1D3 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins.|||Widely expressed (at protein level). http://togogenome.org/gene/10090:Pnn ^@ http://purl.uniprot.org/uniprot/O35691|||http://purl.uniprot.org/uniprot/Q3TUQ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pinin family.|||Found in a mRNA splicing-dependent exon junction complex (EJC). Found in a complex with SR proteins. Found in a mRNP complex with RNPS1. Component of the PSAP complex consisting of RNPS1, SAP18 and PNN. Interacts with PNISR, CTBP1, CTBP2, KRT8, KRT18, KRT19, PS1D/PNO40, PPIG, RNPS1, SFRS4 and SRRM2. Identified in the spliceosome C complex (By similarity).|||Found in a mRNA splicing-dependent exon junction complex (EJC). Found in a complex with SR proteins. Found in a mRNP complex with RNPS1. Component of the PSAP complex consisting of RNPS1, SAP18 and PNN. Interacts with PNISR, CTBP1, CTBP2, KRT8, KRT18, KRT19, PS1D/PNO40, PPIG, RNPS1, SFRS4 and SRRM2. Identified in the spliceosome C complex.|||Nucleus speckle|||Transcriptional activator binding to the E-box 1 core sequence of the E-cadherin promoter gene; the core-binding sequence is 5'CAGGTG-3'. Capable of reversing CTBP1-mediated transcription repression. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Participates in the regulation of alternative pre-mRNA splicing. Associates to spliced mRNA within 60 nt upstream of the 5'-splice sites. Component of the PSAP complex which binds RNA in a sequence-independent manner and is proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. Involved in the establishment and maintenance of epithelia cell-cell adhesion (By similarity).|||desmosome http://togogenome.org/gene/10090:Lmx1b ^@ http://purl.uniprot.org/uniprot/A0A6I8MWW7|||http://purl.uniprot.org/uniprot/O88609 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with DHX9.|||Nucleus|||Transcription factor involved in the regulation of podocyte-expressed genes. Essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels. http://togogenome.org/gene/10090:4931414P19Rik ^@ http://purl.uniprot.org/uniprot/Q8K2W9 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Dnpep ^@ http://purl.uniprot.org/uniprot/Q3TVK3|||http://purl.uniprot.org/uniprot/Q8CAJ7|||http://purl.uniprot.org/uniprot/Q9Z2W0 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aminopeptidase with specificity towards an acidic amino acid at the N-terminus. Likely to play an important role in intracellular protein and peptide metabolism (By similarity).|||Belongs to the peptidase M18 family.|||Binds 2 Zn(2+) ions per subunit.|||Cytoplasm|||One of the zinc ions is readily exchangeable with other divalent cations such as manganese, which strongly stimulates the enzymatic activity.|||Tetrahedron-shaped homododecamer built from six homodimers.|||Ubiquitous. http://togogenome.org/gene/10090:Gcnt7 ^@ http://purl.uniprot.org/uniprot/F8WK01|||http://purl.uniprot.org/uniprot/Q3V3K7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 14 family.|||Glycosyltransferase.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:P2ry13 ^@ http://purl.uniprot.org/uniprot/Q9D8I2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for ADP. Coupled to G(i)-proteins. May play a role in hematopoiesis and the immune system (By similarity). http://togogenome.org/gene/10090:Lin28a ^@ http://purl.uniprot.org/uniprot/Q8K3Y3 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lin-28 family.|||Cytoplasm|||Expressed in embryonic stem cells (ES cells), spermatagonia and testis. Expressed in numerous epithelial tissues including the epithelia of the small intestine, the intralobular duct epithelium of the mammary gland and the epithelia of Henle's loop in the kidney and in the collecting duct (at protein level). Also expressed in the myocardium and skeletal muscle (at protein level).|||Monomer (PubMed:22078496). During skeletal muscle differentiation, associated with translation initiation complexes in the polysomal compartment (By similarity). Directly interacts with EIF3S2 (PubMed:17473174). Interacts with NCL in an RNA-dependent manner (By similarity). Interacts with TUT4 in the presence of pre-let-7 RNA (PubMed:28671666).|||Negatively regulated by the microRNA miR-125b in response to retinoic acid.|||P-body|||RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism (PubMed:17473174, PubMed:18604195, PubMed:18566191, PubMed:18292307, PubMed:19703396, PubMed:23102813, PubMed:24209617). Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (PubMed:26045559). 'Translational enhancer' that drives specific mRNAs to polysomes and increases the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in mRNA stabilization. Binds IGF2 mRNA, MYOD1 mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for skeletal muscle differentiation program through the translational up-regulation of IGF2 expression (PubMed:17473174). Suppressor of microRNA (miRNA) biogenesis, including that of let-7, miR107, miR-143 and miR-200c. Specifically binds the miRNA precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in pre-miRNA terminal loop, and recruits TUT4 and TUT7 uridylyltransferaseS. This results in the terminal uridylation of target pre-miRNAs. Uridylated pre-miRNAs fail to be processed by Dicer and undergo degradation. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state by preventing let-7-mediated differentiation of embryonic stem cells (PubMed:19703396, PubMed:28671666). Localized to the periendoplasmic reticulum area, binds to a large number of spliced mRNAs and inhibits the translation of mRNAs destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins (PubMed:23102813). Binds to and enhances the translation of mRNAs for several metabolic enzymes, such as PFKP, PDHA1 or SDHA, increasing glycolysis and oxidative phosphorylation. Which, with the let-7 repression may enhance tissue repair in adult tissue (PubMed:24209617).|||Reactivation of LIN28A expression enhances tissue repair in some adult tissues by reprogramming cellular bioenergetics. Improves hair regrowth by promoting anagen in hair follicle and accelerates regrowth of cartilage, bone and mesenchyme after ear and digit injuries.|||Rough endoplasmic reticulum|||Stress granule|||Strongly expressed throughout the whole embryo at 6.5 dpc, including the embryonic and extraembryonic ectoderm and endoderm (at protein level). Subsequently expressed in the ectoderm, endoderm and mesoderm at 7.5 dpc (at protein level). At 9.5 dpc, expressed in epithelia covering the first branchial arch and the coelomic cavity, the myocardium of the developing heart, the neuroepithelium and some extraembryonic tissues such as the visceral yolk sac (at protein level). Expression persists in a variety of epithelial tissues at 10.5 dpc. At 15.5 dpc, expression is lost in bronchial epithelium and becomes weaker in neuroepithelium, while increasing in the myotome of somites, the foregut epithelium, stratified epithelium and some kidney tubules (at protein level). At 17.5 dpc, expression persists in the myocardium and in the epithelium covering the body surface and skeletal muscles (at protein level). Expression is reduced during differentiation of ES cells. In adult primary myoblasts, barely detectable during proliferation, but dramatically up-regulated during terminal differentiation. Induced as early as 24 hours after differentiation signal and remains high as late as 7 days of differentiation. Little expression in resting muscle, but strongly up-regulated during regeneration of skeletal muscle fibers. Expression decreases when regeneration is histologically and functionally complete.|||The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members.|||The CSD domain is required for function in muscle differentiation.|||nucleolus http://togogenome.org/gene/10090:Smim23 ^@ http://purl.uniprot.org/uniprot/Q9DAL0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rnf220 ^@ http://purl.uniprot.org/uniprot/Q6PDX6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated; leads to proteasomal degradation.|||Cytoplasm|||E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of SIN3B (PubMed:20170641). Independently of its E3 ligase activity, acts as a CTNNB1 stabilizer through USP7-mediated deubiquitination of CTNNB1 and promotes Wnt signaling (By similarity). Plays a critical role in the regulation of nuclear lamina.|||In the brain, expressed in the hippocampus, telenecephalon and cerebellum. No expression in astro glial cells or in neural progenitor cells.|||Interacts with SIN3B (PubMed:20170641). Interacts with CTNNB1 (via Armadillo repeats 2-8) (By similarity). Interacts with USP7 (via MATH domain) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or4b13 ^@ http://purl.uniprot.org/uniprot/Q60881 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Amy2a2 ^@ http://purl.uniprot.org/uniprot/P00688 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 13 family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 1 Cl(-) ion per subunit.|||Monomer.|||extracellular space http://togogenome.org/gene/10090:Rtbdn ^@ http://purl.uniprot.org/uniprot/Q8QZY4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the folate receptor family.|||Cell membrane|||Expressed in the peripheral retina where it localizes to the inter-photoreceptor matrix (at protein level). May be produced by rod photoreceptors (at protein level).|||Not N-glycosylated.|||Riboflavin-binding protein which might have a role in retinal flavin transport.|||interphotoreceptor matrix http://togogenome.org/gene/10090:Hr ^@ http://purl.uniprot.org/uniprot/Q61645 ^@ Cofactor|||Disease Annotation|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 Fe(2+) ion per subunit.|||Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors (By similarity).|||Defects in Hr are the cause of a number of pleiotropic effects including structural abnormalities of epithelial cells in the hair follicles, hair loss towards the end of the first hair growth cycle, and the failure of subsequent hair growth cycles. Older mice carrying a hr mutation have been reported to possess altered ratios of T-cell-dependent B-cell responses. Mice homozygous for hr mutation are uniquely sensitive to UV and chemically induced skin tumors.|||Expressed predominantly in brain, hair follicles and interfollicular epidermis. No expression in dermis.|||Histone demethylase that specifically demethylates both mono- and dimethylated 'Lys-9' of histone H3. May act as a transcription regulator controlling hair biology (via targeting of collagens), neural activity, and cell cycle.|||Nucleus|||The JmjC domain and the C6-type zinc-finger are required for the demethylation activity. http://togogenome.org/gene/10090:Rint1 ^@ http://purl.uniprot.org/uniprot/Q8BZ36 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RINT1 family.|||Component of the NRZ complex composed of NBAS, ZW10 and RINT1/TIP20L; NRZ associates with SNAREs STX18, USE1L, BNIP1/SEC20L and SEC22B (the assembly has been described as syntaxin 18 complex). Interacts directly with BNIP1/SEC20L and ZW10. Interacts with RAD50 during late S and G2/M phases. Interacts with RBL2, preferentially with the active, hypophosphorylated form (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum; the function is proposed to depend on its association in the NRZ complex which is believed to play a role in SNARE assembly at the ER. May play a role in cell cycle checkpoint control. Essential for telomere length control (By similarity). http://togogenome.org/gene/10090:Zbtb44 ^@ http://purl.uniprot.org/uniprot/Q8R0A2 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Abca2 ^@ http://purl.uniprot.org/uniprot/A2AJ26 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Txndc11 ^@ http://purl.uniprot.org/uniprot/Q8K2W3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum membrane|||Interacts with the cytoplasmic part of DUOX1 and DUOX2. Interacts with TPO and CYBA (By similarity).|||May act as a redox regulator involved in DUOX proteins folding. The interaction with DUOX1 and DUOX2 suggest that it belongs to a multiprotein complex constituting the thyroid H(2)O(2) generating system. It is however not sufficient to assist DUOX1 and DUOX2 in H(2)O(2) generation (By similarity). http://togogenome.org/gene/10090:Kmt2e ^@ http://purl.uniprot.org/uniprot/Q3UG20 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (By similarity). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (By similarity). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (PubMed:18854576, PubMed:18952892, PubMed:18818388). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:19264965). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (By similarity). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (PubMed:19264965).|||Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.|||Chromosome|||Component of a complex composed of KMT2E, OGT and USP7; the complex stabilizes KMT2E, preventing KMT2E ubiquitination and proteasomal-mediated degradation. Interacts (via N-terminus) with OGT (via TRP repeats). Interacts with deubiquitinating enzyme USP7 (via MATH domain). Interacts (via HBM motif) with HCFC1 (via Kelch domain). Interacts with E2F1; the interaction is probably indirect and is mediated via HCFC1.|||Contaminating sequence. Potential poly-A sequence starting in position 486.|||Contaminating sequence. Potential poly-A sequence starting in position 492.|||Contaminating sequence. Potential poly-A sequence starting in position 495.|||Contaminating sequence. Potential poly-A sequence starting in position 803.|||Defects in immunity and hematopoiesis. Adult homozygous mice are obtained at reduced frequency because of postnatal lethality. Surviving animals display a variety of abnormalities, including male infertility, retarded growth and defects in multiple hematopoietic lineages. They also show increased susceptibility to spontaneous eye infections associated with a cell-autonomous impairment of neutrophil function. They exhibit a mild impairment of erythropoiesis and hematopoietic stem cells (HSCs) have impaired competitive repopulating capacity both under normal conditions and when subjected to self-renewal stimulation by NUP98-HOXA10. Homozygous HSCs show a dramatic sensitivity to DNA demethylation-induced differentiation (5-azadeoxycytidine).|||Does not exhibit histone methyltransferase towards histone H3 in vitro (PubMed:18952892). The isolated catalytic SET domain lacks binding activity towards cofactor S-adenosyl-L-methionine; instead of the highly conserved XGXG, Y and NH motifs, KMT2E displays NKKI (Asn-339-Ile-342), F (Phe-381) and RR (Arg-408-Arg-409) motifs. Also lacks binding activity towards histone H3 due to a poor conservation of the key residues involved in the binding and the presence of large loop which prevents the docking of the H3 'Lys-4' side chain.|||Nucleus speckle|||O-glycosylated at Ser-435 and Thr-440 in the SET domain by OGT which probably prevents KMT2E proteasomal-mediated degradation.|||The C-terminus domain is responsible for the localization to the centrosome during mitosis.|||The PHD-type domain binds specifically histone H3 tri-methylated at 'Lys-4' (H3K4me3), thus promoting binding to chromatin.|||The SET domain does not bind the methyl group donor S-adenosyl-L-methionine and histone 3 H3K4 peptide as a large loop prevents the docking of the 'Lys-4' side chain.|||Ubiquitinated. Deubiquitinated by USP7.|||Up-regulated in reversibly arrested C2C12 myoblasts.|||centrosome http://togogenome.org/gene/10090:Pced1b ^@ http://purl.uniprot.org/uniprot/Q8BGX1 ^@ Similarity ^@ Belongs to the PC-esterase family. http://togogenome.org/gene/10090:Armc7 ^@ http://purl.uniprot.org/uniprot/Q3UJZ3 ^@ Function|||Subunit ^@ As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.|||Component of the minor spliceosome. Within this complex, interacts with RBM48. http://togogenome.org/gene/10090:Rnf181 ^@ http://purl.uniprot.org/uniprot/Q9CY62 ^@ Function|||PTM|||Similarity|||Subunit ^@ Auto-ubiquitinated as part of the enzymatic reaction.|||Belongs to the RNF181 family.|||Directly interacts with ITGA2B and, as a result, with integrin ITGA2B/ITGB3. There is no evidence that integrin ITGA2B/ITGB3 is an endogenous substrate for RNF181-directed ubiquitination.|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Catalyzes monoubiquitination of 26S proteasome subunit PSMC2/RPT1. http://togogenome.org/gene/10090:Or10g9b ^@ http://purl.uniprot.org/uniprot/Q8VH08 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Aoc1l3 ^@ http://purl.uniprot.org/uniprot/Q6WIZ7|||http://purl.uniprot.org/uniprot/Q8BZI2 ^@ Cofactor|||PTM|||Similarity ^@ Belongs to the copper/topaquinone oxidase family.|||Contains 1 topaquinone per subunit.|||Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. http://togogenome.org/gene/10090:Sos1 ^@ http://purl.uniprot.org/uniprot/Q62245 ^@ Function|||PTM|||Subunit|||Tissue Specificity ^@ Expressed in most embryonic and adult tissues.|||Interacts (via C-terminus) with GRB2 (via SH3 domain). Forms a complex with phosphorylated MUC1 and GRB2 (via its SH3 domains). Interacts with phosphorylated LAT2. Interacts with NCK1 and NCK2 (By similarity). Part of a complex consisting of ABI1, EPS8 and SOS1 (PubMed:10499589, PubMed:11524436). Interacts (Ser-1120 and Ser-1147 phosphorylated form) with YWHAB and YWHAE (By similarity).|||Phosphorylation at Ser-1120 and Ser-1147 by RPS6KA3 create YWHAB and YWHAE binding sites and which contribute to the negative regulation of EGF-induced MAPK1/3 phosphorylation.|||Promotes the exchange of Ras-bound GDP by GTP. Probably by promoting Ras activation, regulates phosphorylation of MAP kinase MAPK3 in response to EGF (By similarity). Catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity (PubMed:10499589, PubMed:11524436). http://togogenome.org/gene/10090:Cd27 ^@ http://purl.uniprot.org/uniprot/P41272|||http://purl.uniprot.org/uniprot/Q3U4X0 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer. Interacts with SIVA1 and TRAF2 (By similarity).|||In thymus and spleen, but not in non-lymphoid tissues.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for CD70/CD27L. May play a role in survival of activated T-cells. May play a role in apoptosis through association with SIVA1. http://togogenome.org/gene/10090:Cyren ^@ http://purl.uniprot.org/uniprot/Q8BHZ5 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell-cycle-specific regulator of classical non-homologous end joining (NHEJ) of DNA double-strand break (DSB) repair, which can act both as an activator or inhibitor of NHEJ, depending on the cell cycle phase (PubMed:30017584). Acts as a regulator of DNA repair pathway choice by specifically inhibiting classical NHEJ during the S and G2 phases, thereby promoting error-free repair by homologous recombination during cell cycle phases when sister chromatids are present (By similarity). Preferentially protects single-stranded overhangs at break sites by inhibiting classical NHEJ, thereby creating a local environment that favors homologous recombination (By similarity). Acts via interaction with XRCC5/Ku80 and XRCC6/Ku70 (By similarity). In contrast, acts as an activator of NHEJ during G1 phase of the cell cycle: promotes classical NHEJ in G1 phase cells via multivalent interactions that increase the affinity of DNA damage response proteins for DSB-associated chromatin (PubMed:30017584). Also involved in immunoglobulin V(D)J recombination (PubMed:30017584, PubMed:31795137). May also act as an indirect regulator of proteasome (By similarity).|||Chromosome|||Cytoplasm|||Interacts (via KBM motif) with XRCC5/Ku80 and XRCC6/Ku70 heterodimer (PubMed:30017584). Interacts (via XLF motif) with TRIM28/KAP1, ATM, MRE11, NBN and RAD50 (PubMed:30017584).|||No visible phenotype in normal conditions: mice are fertile, do not show any gross abnormalities and do not develop spontaneous cancers (PubMed:30017584, PubMed:31795137). Mice have normal numbers of B- and T-cells, but show defects in class switch recombination in primary B-cells (PubMed:30017584, PubMed:31795137). Mice lacking both Cyren and Nhej1/Xlf show embryonic lethality caused by severe defects in classical non-homologous end joining (NHEJ) (PubMed:30017584).|||Nucleus|||The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites.|||The XLM (XLF-like motif) mediates interaction with DNA damage response proteins TRIM28/KAP1, ATM and members of the MRN complex (MRE11, NBN and RAD50). http://togogenome.org/gene/10090:Tbpl1 ^@ http://purl.uniprot.org/uniprot/P62340 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBP family.|||Binds TFIIA and TFIIB.|||Cytoplasm|||Nucleus|||Part of a specialized transcription system that mediates the transcription of most ribosomal proteins through the 5'-TCT-3' motif which is a core promoter element at these genes (By similarity). Seems to also mediate the transcription of NF1. Does not bind the TATA box.|||Significantly reduced NF1 levels.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Rfesd ^@ http://purl.uniprot.org/uniprot/Q8K2P6 ^@ Cofactor ^@ Binds 1 [2Fe-2S] cluster per subunit. http://togogenome.org/gene/10090:Or7g25 ^@ http://purl.uniprot.org/uniprot/Q7TRG4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gorasp2 ^@ http://purl.uniprot.org/uniprot/Q99JX3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GORASP family.|||Detected in lung, heart and testis. Colocalized in a polarized fashion in the acrosome region with JAM3 in round spermatids (at protein level).|||Endoplasmic reticulum membrane|||Golgi apparatus|||Golgi apparatus membrane|||Homodimer. Homooligomer. ER stress induces phosphorylation-dependent monomerization (By similarity). Interacts with BLZF1/Golgin 45 (PubMed:11739401, PubMed:28049725). Identified in a complex with RAB2 and GORASP2 (PubMed:11739401). Interacts with JAM2 and JAM3 (PubMed:28617811). Interacts with members of the p24 cargo receptors. Interacts with CNIH and the cytoplasmic domain of transmembrane TGFA, prior its transit in the trans-Golgi. Interacts with KCTD5 (By similarity). Interacts with TMED2 and TMED3 (By similarity). Interacts with SEC16A in response to ER stress (By similarity). Interacts (via PDZ GRASP-type 1 domain) with core-glycosylated CFTR in response to ER stress (By similarity).|||Key structural protein of the Golgi apparatus (PubMed:32573693). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon (PubMed:32573693). Acting in concert with GORASP1/GRASP65, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks (PubMed:32573693). However, other studies suggest that GORASP2 plays a role in assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after breakdown during mitosis and meiosis (By similarity). May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA (By similarity). Required for normal acrosome formation during spermiogenesis and normal male fertility, probably by promoting colocalization of JAM2 and JAM3 at contact sites between germ cells and Sertoli cells (PubMed:28617811). Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (By similarity).|||Mutant mice have normal weight at birth, but display growth retardation and lower body weight during postnatal development and in adulthood. Females display normal fertility. Males have normal mating behavior, but are infertile, due to defects in spermiogenesis and acrosome formation.|||Myristoylated (By similarity). Myristoylation is essential for the Golgi targeting (By similarity).|||Palmitoylated.|||Phosphorylated in mitotic cells. ER stress-induced phosphorylation at Ser-443 induces monomerization and subsequent relocalization from Golgi to ER which is essential for mediating unconventional (ER/Golgi-independent) trafficking of CFTR to the cell membrane. http://togogenome.org/gene/10090:Qprt ^@ http://purl.uniprot.org/uniprot/Q91X91 ^@ Function|||Similarity|||Subunit ^@ Belongs to the NadC/ModD family.|||Hexamer formed by 3 homodimers.|||Involved in the catabolism of quinolinic acid (QA). http://togogenome.org/gene/10090:Zmat5 ^@ http://purl.uniprot.org/uniprot/Q9CQR5 ^@ Subcellular Location Annotation|||Subunit ^@ Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Not found in the major spliceosome (By similarity).|||Nucleus http://togogenome.org/gene/10090:Chchd6 ^@ http://purl.uniprot.org/uniprot/E9Q4M4|||http://purl.uniprot.org/uniprot/Q91VN4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MICOS complex subunit Mic19 family. Metazoan Mic25 subfamily.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with DISC1. Interacts with IMMT/MIC60.|||Membrane|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gm13275 ^@ http://purl.uniprot.org/uniprot/B1AYI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Etfb ^@ http://purl.uniprot.org/uniprot/Q9DCW4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ETF beta-subunit/FixA family.|||Heterodimer composed of ETFA and ETFB. Identified in a complex that contains ETFA, ETFB and ETFRF1. Interacts with ACADM.|||Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (By similarity). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:25023281). ETFB binds an AMP molecule that probably has a purely structural role (By similarity).|||Methylated (PubMed:25023281). Trimethylation at Lys-200 and Lys-203 may negatively regulate the activity in electron transfer from acyl-CoA dehydrogenases.|||Mitochondrion matrix|||The recognition loop recognizes a hydrophobic patch at the surface of interacting dehydrogenases and acts as a static anchor at the interface. http://togogenome.org/gene/10090:Hmx3 ^@ http://purl.uniprot.org/uniprot/P42581 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Begins at embryonic day 10.5 in the developing ear, hypothalamus, the neural tube and dorsal root ganglia. It continues to be active throughout prenatal life in discrete regions of the brain with an anterior border in the ventral diencephalon at the optic chiasma and expression domains in mesencephalon, metencephalon, and myelencephalon. At midgestation, it is also expressed in mesenchyme of the head and branchial arches, and in some cranial ganglia, as well as in derivatives of neural crest, such as the truncus sympathicus and myenteric ganglia. In inner ear, it is expressed between 13.5 dpc and birth in non-sensory epithelium of the semicircular canals, utricle and saccule. Also expressed in the cochlea, where the expression is restricted to the stria vascularis.|||Belongs to the HMX homeobox family.|||Chimeric cDNA.|||Expressed in the developing CNS, including a specific expression in vestibular structures throughout inner ear development.|||Mice display abnormal circling behavior and severe vestibular defects owing to a depletion of sensory cells in the saccule and utricle, and a complete loss of the horizontal semicircular canal crista, as well as a fusion of the utricle and saccule endolymphatic spaces into a common utriculosaccular cavity. Moreover, most females have a reproductive defect: females can be fertilized and their embryos undergo normal preimplantation development, but the embryos fail to implant successfully in the uterus and subsequently die. Mice lacking both Hmx2 and Hmx3 show a complete loss of balance, postnatal dwarfism, defects in neuroendocrine system, disturbed hypothalamic-pituitary axis and subsequent die. Defects caused in mice lacking both Hmx2 and Hmx3 can be rescued by expressing the Drosophila Hmx protein.|||Nucleus|||Regulated by Six1 and FGFs in inner ear.|||Transcription factor involved in specification of neuronal cell types and which is required for inner ear and hypothalamus development. Binds to the 5'-CAAGTG-3' core sequence. Controls semicircular canal formation in the inner ear. Also required for hypothalamic/pituitary axis of the CNS. http://togogenome.org/gene/10090:Slc25a13 ^@ http://purl.uniprot.org/uniprot/Q8C140|||http://purl.uniprot.org/uniprot/Q9QXX4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, expressed in branchial arches, a well as in the limb and tail buds. At 13.5 dpc expression is predominant in epithelial structures and the forebrain, kidney and liver. Expression in liver is maintained into adulthood.|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Homodimer (via N-terminus).|||Membrane|||Mitochondrial electrogenic aspartate/glutamate antiporter that favors efflux of aspartate and entry of glutamate and proton within the mitochondria as part of the malate-aspartate shuttle (By similarity). Also mediates the uptake of L-cysteinesulfinate by mitochondria in exchange of L-glutamate and proton. Can also exchange L-cysteinesulfinate with aspartate in their anionic form without any proton translocation (By similarity).|||Mitochondrion inner membrane|||The EF-hand 2 domain within the regulatory N-terminal domain binds one calcium in the mitochondrial intermembrane space. Calcium triggers the binding of the regulatory N-terminal domain to the C-terminal domain, opening a vestibule which allows the substrates to be translocated through the carrier domain (By similarity). In the absence of calcium, the linker loop domain may close the vestibule and prevent substrates from entering the carrier domain (By similarity). http://togogenome.org/gene/10090:Spz1 ^@ http://purl.uniprot.org/uniprot/Q99MY0 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Down-regulated by testosterone and retinoic acid.|||Expressed specifically in the testis and epidydimis. In the testis expressed in both germ cells and somatic cells (Sertoli and Leydig cells). Expressed in several tumor cell lines.|||First detected in the testis at postnatal day 10 and levels increase further and reach highest levels at day 40 and then gradually decrease.|||Interacts with PPP1CC isoform gamma-2. This interaction can prevent SPZ1 binding to the E-box and inhibits PPP1CC activity.|||Nucleus|||Phosphorylated by MAPK1/ERK2 and MAPK3/ERK1.|||The helix-loop-helix and basic motifs form a Spz1 specific bHLH different from the classical one.|||Transcription factor that binds to the DNA sequence 5'-CANNTG-3'(E box) and the G-box motif. Directly binds to a guanine-rich region of the PCNA promoter and up-regulates its expression which in turn induces cell transformation and tumor formation. May play an important role in the regulation of cell proliferation and differentiation during spermatogenesis. http://togogenome.org/gene/10090:Dyrk2 ^@ http://purl.uniprot.org/uniprot/Q5U4C9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by autophosphorylation on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop.|||Autophosphorylates cotranslationally on the second tyrosine residue in the Tyr-X-Tyr motif in the activation loop, but once mature, does not have any protein tyrosine kinase activity. Phosphorylated at Thr-104 and Ser-440 by ATM in response to genotoxic stress.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.|||Component of an E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 (EDVP complex). Interacts directly with EDD/UBR5, DDB1 and DCAF1. Interacts with SIAH2 and MDM2. Interacts with MAP3K10 and NFATC1. May also interact with CCNL2 (By similarity).|||Cytoplasm|||Nucleus|||Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro) (By similarity). Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX.|||Under normal conditions, polyubiquitinated in the nucleus by MDM2, leading to its proteasomal degradation. Phosphorylation on Thr-104 and Ser-440 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation. Polyubiquitinated by SIAH2, leading to its proteasomal degradation. Polyubiquitinated by SIAH2 occurs under normal conditions, and is enhanced in response to hypoxia. http://togogenome.org/gene/10090:Frmd7 ^@ http://purl.uniprot.org/uniprot/A2AD83 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ In the developing cerebral cortex, strong expression is observed in the ventricular and intermediate zones at 13 and 17 dpc. At 17 dpc and P0, expression appears to be restricted to the cortical plate. In neonates, highly expressed in cortex, hippocampus, cerebellum, olfactory bulb and eye with little or no expression in liver, kidney, skeletal muscle or heart muscle (at protein level).|||Plays a role in neurite development, may be through the activation of the GTPase RAC1. Plays a role in the control of eye movement and gaze stability.|||Up-regulated during retinoic acid-induced differentiation of neuroblastoma cells.|||growth cone|||neuron projection http://togogenome.org/gene/10090:Prop1 ^@ http://purl.uniprot.org/uniprot/P97458 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the paired homeobox family.|||Nucleus|||Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes. http://togogenome.org/gene/10090:Tmem276 ^@ http://purl.uniprot.org/uniprot/P0DW86 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cep295nl ^@ http://purl.uniprot.org/uniprot/Q497N6 ^@ Developmental Stage|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed during the postmeiotic stages of spermatogenesis. Detected at least at 14 dpc, the expression being enriched in kidney and small intestine. Within the nervous system, expression is prominent in the most superficial layers of the posterior cerebral cortex at 14 dpc and retina at 18 dpc. Expression is enriched in the posterior cerebral cortex at birth and declines at 7 days after birth.|||Expressed in mature spermatozoa (at protein level). Detected in retina, lung and kidney. In brain, highly expressed in brain-stem, cerebral cortex and thalamus with lesser expression in cerebellum and hippocampus.|||Expression is moderately up-regulated 2 days after intracranial injury and increases at 4 and 7 days post-injury.|||cilium http://togogenome.org/gene/10090:Plod3 ^@ http://purl.uniprot.org/uniprot/Q9R0E1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in blood serum, heart, brain, liver, kidney, lung, spleen, muscle and testis (at protein level) (PubMed:16447251). Highly expressed in the heart, lung, liver and testis (PubMed:10429951). Detected in the walls of blood vessels in placenta and embryos. Detected in chondrocytes in embryos at 14.5 dpc and in adults, in adult kidney mesangium and vascular poles of kidney glomeruli (PubMed:15377789). Detected around nerves and in the adrenal gland (PubMed:15377789).|||Detected in embryos (at protein level) (PubMed:16467571). Ubiquitous and strongly expressed in embryos at 8.5 to 9.5 dpc. Expression becomes more restricted during embryonic development. Highly expressed in head, eye lens and developing bones at 12.5 dpc. Expression in the eye is decreased by 14.5 dpc. Detected in capillaries and in the photoreceptor layer in the adult eye (PubMed:15377789).|||Endoplasmic reticulum lumen|||Endoplasmic reticulum membrane|||Full embryonic lethality. Mutant embryos are much smaller than wild-type by 9.5 dpc, and the majority are dead by 10.5 dpc. At 9.5 dpc, mutant embryos display fragmentation of basement membranes (PubMed:15377789, PubMed:16467571). The majority of the mutant embryos display dilated blood vessels, particularly in the region of the sinus venosus (PubMed:16467571). Mutant embryos display no decrease in global lysyl hydroxylase activity, due to the expression of other lysyl hydroxylases (PubMed:15377789). Mutant embryos display a nearly complete loss of procollagen glucosyltransferase activity (PubMed:15377789, PubMed:16467571).|||Homodimer.|||Multifunctional enzyme that catalyzes a series of post-translational modifications on Lys residues in procollagen (PubMed:16447251). Plays a redundant role in catalyzing the formation of hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens (PubMed:16447251). Plays a redundant role in catalyzing the transfer of galactose onto hydroxylysine groups, giving rise to galactosyl 5-hydroxylysine (By similarity). Has an essential role by catalyzing the subsequent transfer of glucose moieties, giving rise to 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:16447251, PubMed:16467571, PubMed:21220425). Catalyzes hydroxylation and glycosylation of Lys residues in the MBL1 collagen-like domain, giving rise to hydroxylysine and 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:25419660). Catalyzes hydroxylation and glycosylation of Lys residues in the ADIPOQ collagen-like domain, giving rise to hydroxylysine and 1,2-glucosylgalactosyl-5-hydroxylysine residues (PubMed:23209641). Essential for normal biosynthesis and secretion of type IV collagens (PubMed:15377789, PubMed:16467571, PubMed:17873278). Essential for normal formation of basement membranes (PubMed:15377789, PubMed:16467571).|||N-glycosylated.|||Rough endoplasmic reticulum|||Secreted|||The C-terminal domain that mediates lysyl hydroxylase activity is also important for homodimerization.|||The N-terminal domain mediates glycosyltransferase activity.|||extracellular space http://togogenome.org/gene/10090:Htr7 ^@ http://purl.uniprot.org/uniprot/B6VJS3|||http://purl.uniprot.org/uniprot/P32304 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. http://togogenome.org/gene/10090:Apoa4 ^@ http://purl.uniprot.org/uniprot/P06728 ^@ Domain|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the apolipoprotein A1/A4/E family.|||Homodimer.|||May have a role in chylomicrons and VLDL secretion and catabolism. Required for efficient activation of lipoprotein lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major component of HDL and chylomicrons.|||Nine of the thirteen 22-amino acid tandem repeats (each 22-mer is actually a tandem array of two, A and B, related 11-mers) occurring in this sequence are predicted to be highly alpha-helical, and many of these helices are amphipathic. They may therefore serve as lipid-binding domains with lecithin:cholesterol acyltransferase (LCAT) activating abilities.|||Secreted|||Secreted in plasma.|||There is a polymorphism within a series of imperfect repeats encoding the sequence E-Q-[AV]-Q. Insertions or deletions of 12 nucleotides have given rise to three forms characterized by three (129), four (C57BL/6), or five (M.castaneus) copies of the repeat unit. http://togogenome.org/gene/10090:Pinx1 ^@ http://purl.uniprot.org/uniprot/Q9CZX5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PINX1 family.|||Interacts with MCRS1, TERT, TERF1, NCL/nucleolin, and the telomerase RNA.|||Microtubule-binding protein essential for faithful chromosome segregation. Mediates TRF1 and TERT accumulation in nucleolus and enhances TRF1 binding to telomeres. Inhibits telomerase activity. May inhibit cell proliferation and act as tumor suppressor (By similarity).|||Nucleus|||The TBM domain mediates interaction with TERF1.|||The TID (telomerase inhibiting domain) domain is sufficient to bind TERT and inhibits its activity.|||kinetochore|||nucleolus|||telomere http://togogenome.org/gene/10090:Akap17b ^@ http://purl.uniprot.org/uniprot/A2A3V1 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Talia' means 'waistline' in Polish.|||Monomer. Component of the spliceosome (By similarity).|||Nucleus speckle|||Splice factor regulating alternative splice site selection for certain mRNA precursors.|||Ubiquitously expressed.|||Uniformally expressed in the extraembryonic ectoderm at 5.5 dpc. Restricted to the distal part of the extraembryonic ectoderm at 6.5 dpc-7.5 dpc. http://togogenome.org/gene/10090:Diras1 ^@ http://purl.uniprot.org/uniprot/Q91Z61 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Di-Ras family.|||Cell membrane|||Displays low GTPase activity and exists predominantly in the GTP-bound form. http://togogenome.org/gene/10090:Sapcd2 ^@ http://purl.uniprot.org/uniprot/Q9D818 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cytoplasm|||Expressed in the embryonic retina from 14 to 17 dpc (at protein level) (PubMed:26766442). Expressed throughout neuroectoderm at 7.5 dpc (PubMed:15567712). The expression increases in rostral brain and caudal neuropore regions and decreases in hindbrain and spinal cord regions (PubMed:15567712). At 12.5 dpc the expression is found in undifferentiated neuroepithelium in ventricular zone, dorsal root ganglia and several non-neural tissues (PubMed:15567712).|||Expressed in the retina (PubMed:26766442). Expressed in retinal progenitor cells and newly differentiated neurons but not in mature retinal cells (at protein level) (PubMed:26766442).|||Interacts with a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1. Interacts with GPSM2 (via TPR motifs); this interaction is required to prevent GPSM2 anchoring at the mitotic apical cortex and is inhibited in presence of NUMA1 in a dose dependent manner. Interacts with PARD3.|||Nucleus|||Plays a role in planar mitotic spindle orientation in retinal progenitor cells (RPCs) and promotes the production of symmetric terminal divisions (PubMed:26766442). Negatively regulates the mitotic apical cortex localization of GPSM2 (By similarity). Involved also in positive regulation of cell proliferation and tumor cell growth (By similarity).|||cell cortex|||tight junction http://togogenome.org/gene/10090:Slc44a5 ^@ http://purl.uniprot.org/uniprot/Q5RJI2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CTL (choline transporter-like) family.|||Cell membrane|||Choline/H+ antiporter. http://togogenome.org/gene/10090:Atp2c2 ^@ http://purl.uniprot.org/uniprot/A7L9Z8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway. Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (By similarity). Induces Ca(2+) influx independently of its ATP-driven pump function. At the basolateral membrane of mammary epithelial cells, interacts with Ca(2+) channel ORAI1 and mediates Ca(2+) entry independently of the Ca(2+) content of endoplasmic reticulum or Golgi stores. May facilitate transepithelial transport of large quantities of Ca(2+) for milk secretion via activation of Ca(2+) influx channels at the plasma membrane and active Ca(2+) transport at the Golgi apparatus (PubMed:23840669) (By similarity).|||Basolateral cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.|||Cell membrane|||Expressed in hippocampal neurons (at protein level) (PubMed:15677451). Expressed in lactating mammary epithelium (at protein level) (PubMed:23840669).|||Interacts (via N-terminus) with ORAI1 (via N- and C-termini); this interaction regulates Ca(2+) influx at the plasma membrane.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Timp1 ^@ http://purl.uniprot.org/uniprot/P12032 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protease inhibitor I35 (TIMP) family.|||Found in fetal and adult tissues. Highest levels are found in bone. Also found in lung, ovary and uterus.|||Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very low affinity for MMP14 (By similarity). Interacts with CD63; identified in a complex with CD63 and ITGB1.|||Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14 (By similarity). Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling.|||N-glycosylated.|||Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.|||Regulated by tumor promoters and mitogens through protein kinase C. Also induced by viruses.|||Secreted|||The activity of TIMP1 is dependent on the presence of disulfide bonds. http://togogenome.org/gene/10090:Gpd1 ^@ http://purl.uniprot.org/uniprot/P13707 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.|||Cytoplasm|||Has glycerol-3-phosphate dehydrogenase activity.|||Homodimer. http://togogenome.org/gene/10090:Fhdc1 ^@ http://purl.uniprot.org/uniprot/Q3ULZ2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain, heart and lung (at protein level).|||Golgi apparatus|||Interacts with CEP170.|||Microtubule-associated formin which regulates both actin and microtubule dynamics. Induces microtubule acetylation and stabilization and actin stress fiber formation (PubMed:18815276). Regulates Golgi ribbon formation (PubMed:26564798). Required for normal cilia assembly. Early in cilia assembly, may assist in the maturation and positioning of the centrosome/basal body, and once cilia assembly has initiated, may also promote cilia elongation by inhibiting disassembly (PubMed:29742020).|||The FH2 and MBD domains are essential for its function in regulating Golgi ribbon formation.|||cilium http://togogenome.org/gene/10090:Rpusd2 ^@ http://purl.uniprot.org/uniprot/Q149F1 ^@ Function|||Similarity ^@ Belongs to the pseudouridine synthase RluA family.|||Pseudouridine synthase that catalyzes pseudouridylation of mRNAs. http://togogenome.org/gene/10090:Uchl1 ^@ http://purl.uniprot.org/uniprot/Q9R0P9 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C12 family.|||By LPS, whereas stimulation with IFN-gamma decreases expression.|||Cytoplasm|||Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis (PubMed:31492742, PubMed:32494592, PubMed:37215988). Abrogates the ubiquitination of multiple proteins including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor protein cleaving enzyme 1/BACE1. In addition, recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin to maintain a stable pool of monoubiquitin that is a key requirement for the ubiquitin-proteasome and the autophagy-lysosome pathways (By similarity). Regulates amyloid precursor protein/APP processing by promoting BACE1 degradation resulting in decreased amyloid beta production (By similarity). Plays a role in the immune response by regulating the ability of MHC I molecules to reach cross-presentation compartments competent for generating Ag-MHC I complexes (PubMed:31492742). Mediates the 'Lys-48'-linked deubiquitination of the transcriptional coactivator WWTR1/TAZ leading to its stabilization and inhibition of osteoclastogenesis (PubMed:37215988). Deubiquitinates and stabilizes epidermal growth factor receptor EGFR to prevent its degradation and to activate its downstream mediators (PubMed:32494592). Modulates oxidative activity in skeletal muscle by regulating key mitochondrial oxidative proteins (PubMed:33137160). Enhances the activity of hypoxia-inducible factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated ubiquitination and consequently inhibiting its degradation (By similarity).|||Endoplasmic reticulum membrane|||Expressed in brain, where it is found in neurons but not in oligodendrocytes or astrocytes. Found in the ganglion cell layer and the inner nuclear layer of the retina (at protein level). Expressed in brain and testis. In the brain, expression is at its lowest in replaceable neurons of hippocampus and olfactory bulb. Highly expressed in senescent pituitary. In skeletal muscle, primarily expressed in oxidative muscle fibers (PubMed:33137160).|||In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8.|||Mice show sensory ataxia at an early stage, followed by motor ataxia at a later stage. They have reduced levels of monoubiquitin in the nervous system, and increased resistance to retinal ischemia. In addition, a significant reduction in the generation and proliferation of Ag-specific CD8, but not CD4, T-cells is observed showing that the deletion affects the ability to mount an Ag-specific CD8 T-cell response (PubMed:31492742). UCHL1-skeletal muscle specific gene knockout leads to reduced oxidative muscle fibers and oxidative activity (PubMed:33137160).|||Monomer. Homodimer. Interacts with COPS5 and SNCA (By similarity).|||O-glycosylated.|||The homodimer may have ATP-independent ubiquitin ligase activity. However, in another study, UCHL1 was shown to lack ubiquitin ligase activity. http://togogenome.org/gene/10090:Sike1 ^@ http://purl.uniprot.org/uniprot/Q9CPR7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SIKE family.|||Cytoplasm|||Interacts with IKBKE and TBK1 via its coiled coil region. Interaction with TBK1 is disrupted upon viral infection or TLR3 stimulation. Interacts with CDC42BPB.|||Physiological suppressor of IKK-epsilon and TBK1 that plays an inhibitory role in virus- and TLR3-triggered IRF3. Inhibits TLR3-mediated activation of interferon-stimulated response elements (ISRE) and the IFN-beta promoter. May act by disrupting the interactions of IKBKE or TBK1 with TICAM1/TRIF, IRF3 and RIGI. Does not inhibit NF-kappa-B activation pathways (By similarity). http://togogenome.org/gene/10090:Ddit3 ^@ http://purl.uniprot.org/uniprot/P35639|||http://purl.uniprot.org/uniprot/Q3V405 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family.|||By various stress, such as oxidative stress, amino-acid deprivation, hypoxia and ER stress (PubMed:16670335, PubMed:19752026, PubMed:19855386, PubMed:19919955, PubMed:21159964, PubMed:22242125). Specifically produced in response to stress: in absence of stress, AltDDIT3, the upstream ORF of this bicistronic gene, is translated, thereby preventing its translation (PubMed:21285359). During ER stress, induced by a EIF2AK3/ATF4 pathway and/or ERN1/ATF6 pathway (PubMed:19855386, PubMed:21159964). Expression is suppressed by TLR-TRIF signaling pathway during prolonged ER stress (PubMed:16670335, PubMed:19752026, PubMed:19855386, PubMed:19919955, PubMed:21159964, PubMed:22242125).|||Cytoplasm|||Heterodimer.|||Heterodimer. Interacts with TCF7L2/TCF4, EP300/P300, HDAC5 and HDAC6 (By similarity). Interacts with TRIB3 which blocks its association with EP300/P300 (By similarity). Interacts with FOXO3, and CEBPB (By similarity). Interacts with ATF4 (PubMed:23624402). Interacts with HDAC1 (PubMed:22242125).|||Interacts with isoform AltDDIT3 of DDIT3.|||Multifunctional transcription factor in ER stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes. Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes. Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L. Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity. Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response.|||Multifunctional transcription factor in endoplasmic reticulum (ER) stress response (PubMed:15601821, PubMed:19752026). Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress (PubMed:15601821, PubMed:19752026). Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein (C/EBP) function and as an activator of other genes (PubMed:1547942). Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes (PubMed:1547942). Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L (PubMed:12706815, PubMed:15775988, PubMed:21159964, PubMed:14684614, PubMed:19919955). Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase (ASNS), CEBPA-dependent transcriptional activation of hepcidin (HAMP) and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma (PPARG) (By similarity). Together with ATF4, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (PubMed:22242125, PubMed:23624402). Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity (By similarity). Plays a regulatory role in the inflammatory response through the induction of caspase-11 (CASP4/CASP11) which induces the activation of caspase-1 (CASP1) and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response (PubMed:16670335). Acts as a major regulator of postnatal neovascularization through regulation of endothelial nitric oxide synthase (NOS3)-related signaling (PubMed:22265908).|||Nucleus|||Phosphorylation at serine residues by MAPK14 enhances its transcriptional activation activity while phosphorylation at serine residues by CK2 inhibits its transcriptional activation activity.|||The N-terminal region is necessary for its proteasomal degradation, transcriptional activity and interaction with EP300/P300.|||Ubiquitinated, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:P2rx1 ^@ http://purl.uniprot.org/uniprot/P51576 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the P2X receptor family.|||Homo- or heteropolymers.|||Ligand-gated ion channel with relatively high calcium permeability. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Seems to be linked to apoptosis, by increasing the intracellular concentration of calcium in the presence of ATP, leading to programmed cell death (By similarity).|||Membrane http://togogenome.org/gene/10090:Ank1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1N7|||http://purl.uniprot.org/uniprot/B7ZW98|||http://purl.uniprot.org/uniprot/D3YTV8|||http://purl.uniprot.org/uniprot/D3Z5M4|||http://purl.uniprot.org/uniprot/E9QNT8|||http://purl.uniprot.org/uniprot/G5E8J2|||http://purl.uniprot.org/uniprot/Q02357|||http://purl.uniprot.org/uniprot/Q0VGY9 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acylated by palmitic acid group(s).|||Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with a number of integral membrane proteins and cytoskeletal proteins. Interacts (via N-terminus) with SPTB/spectrin (beta chain). Also interacts with TTN/titin. Isoform Mu17 interacts with OBSCN isoform 3/obscurin. Interacts with HIF1AN. Interacts (via ANK 1-5 repeats) with RHCE; this interaction mediates the primary membrane attachment site for ANK1. Interacts (via ANK 1-2 repeats) with AQP1 (via the N-terminal). Interacts (via ANK 1-13 repeats) with EPB42. Interacts directly with SLC4A1 (via the cytoplasmic domain); this interaction is mediated by the SLC4A1 Band 3-II and Band 3-III dimers.|||Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane. Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.|||Hydroxylated by HIF1AN at several asparagine and 1 aspartate residue within ANK repeat region; hydroxylation seems to increase the conformational stability of this region and may also modulate protein-protein interactions mediated by the ANK repeat region.|||Incomplete sequence. Produced by alternative splicing of isoform Er1.|||Membrane|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform Er1.|||Produced by alternative splicing of isoform Mu7.|||Regulated by phosphorylation.|||Sarcoplasmic reticulum|||The 55 kDa regulatory domain is involved in regulating binding of SPTB/spectrin (beta chain) and SLC4A1/erythrocyte membrane protein band 3.|||The ANK repeat region forms a spiral around a large central cavity and is involved in binding of ion transporters. Adopts a T-shaped arrangement, in the ankyrin-1 complex, in which ANK 1-5 repeats are orthogonal to ANK 6-24 repeats, with the peptide binding groove of ANK 1-5 repeats oriented toward the membrane. The rearrangement of the ANK 1-5 repeats orients the canonical protein binding groove to directly face the membrane, to interact the membrane-embedded targets RHCE and AQP1.|||The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin's function other than binding to spectrin (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Tnfsf9 ^@ http://purl.uniprot.org/uniprot/P41274|||http://purl.uniprot.org/uniprot/Q3U1Z9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages.|||Homotrimer.|||Membrane http://togogenome.org/gene/10090:Ints14 ^@ http://purl.uniprot.org/uniprot/Q8R3P6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the INTS14 family.|||Nucleus|||Probable component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. http://togogenome.org/gene/10090:Smim8 ^@ http://purl.uniprot.org/uniprot/Q9CQQ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMIM8 family.|||Membrane http://togogenome.org/gene/10090:Bmt2 ^@ http://purl.uniprot.org/uniprot/Q8BXK4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the BMT2 family.|||Interacts with the GATOR1 complex; interaction is disrupted when BMT2/SAMTOR binds S-adenosyl-L-methionine. Interacts with the KICSTOR complex; interaction is disrupted when BMT2/SAMTOR binds S-adenosyl-L-methionine.|||S-adenosyl-L-methionine-binding protein that acts as an inhibitor of mTORC1 signaling via interaction with the GATOR1 and KICSTOR complexes. Acts as a sensor of S-adenosyl-L-methionine to signal methionine sufficiency to mTORC1: in presence of methionine, binds S-adenosyl-L-methionine, leading to disrupt interaction with the GATOR1 and KICSTOR complexes and promote mTORC1 signaling. Upon methionine starvation, S-adenosyl-L-methionine levels are reduced, thereby promoting the association with GATOR1 and KICSTOR, leading to inhibit mTORC1 signaling. Probably also acts as a S-adenosyl-L-methionine-dependent methyltransferase. http://togogenome.org/gene/10090:Grifin ^@ http://purl.uniprot.org/uniprot/Q9D1U0 ^@ Domain|||Subunit ^@ Homodimer.|||The galectin domain is atypical and does not bind beta-galactoside sugars. http://togogenome.org/gene/10090:Abcb4 ^@ http://purl.uniprot.org/uniprot/P21440 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.|||Cell membrane|||Cytoplasm|||Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi between hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:8106172, PubMed:7912658, PubMed:7592705, PubMed:7814632, PubMed:8725158, PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (By similarity). Required for proper phospholipid bile formation (PubMed:8106172). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:7814632, PubMed:8725158). May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (PubMed:1990275).|||Expressed in the liver (PubMed:1381362, PubMed:8615769) (at protein level). Expressed in adrenal, liver, muscle, spleen and heart (PubMed:2471060). Expressed in multidrug-resistant cell lines (PubMed:1969609).|||Glycosylated.|||May interact with RACK1. Interacts with HAX1.|||Membrane raft|||Mice show severe necrotic damage of hepatocytes, strong portal inflammation, proliferation and destruction of the canalicular and small bile ductular tracts (PubMed:8106172). Display almost complete reduction of biliary phospholipid secretion, although bile salt secretion is normal (PubMed:8106172, PubMed:7814632, PubMed:8725158, PubMed:9366571). Show also reduced cholesterol secretion (PubMed:8106172, PubMed:9366571). Knockout mice lacking both ABCB4 and ATP8B1 show lower hepatic damage compared with the single ABCB4 knockout mice (PubMed:21820390). Display equivalent reduction of biliary phosphatidylcholine (PC) secretion as the single ABCB4 knockout mice (PubMed:21820390). Biliary cholesterol secretion is higher compared to the single ABCB4 knockout mice (PubMed:21820390). Bile salt secretion is normal in both single ABCB4 knockout mice and double ABCB4 and ATP8B1 knockout mice (PubMed:21820390). Biliary excretion of canalicular ectoenzymes, aminopeptidase N and alkaline phosphatase is strongly reduced compared to single ATP8B1 knockout mice (PubMed:21820390).|||Phosphorylated. Phosphorylation is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner. May be phosphorylated on Thr-41 and Ser-46.|||Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:7912658). Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:7592705).|||Up-regulated by compounds that cause peroxisome proliferation, such as ciprofibrate and clofibrate (at protein level) (PubMed:8615769). Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, ciprofibrate, clofibrate, bezafibrate and gemfibrozil (PubMed:8615769, PubMed:12381268).|||clathrin-coated vesicle http://togogenome.org/gene/10090:Crocc2 ^@ http://purl.uniprot.org/uniprot/F6XLV1 ^@ Similarity ^@ Belongs to the rootletin family. http://togogenome.org/gene/10090:Ddr1 ^@ http://purl.uniprot.org/uniprot/Q03146|||http://purl.uniprot.org/uniprot/Q05BN5|||http://purl.uniprot.org/uniprot/Q544T2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated in response to fibrillar collagen binding.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Detected in the cochlea and the organ of Corti in the inner ear. Isoform 1 is predominant and is expressed in developing embryo and adult brain. Isoform 2 is expressed in various epithelial cells.|||Homodimer. Interacts (via PPxY motif) with WWC1 (via WW domains) in a collagen-regulated manner. Forms a tripartite complex with WWC1 and PRKCZ, but predominantly in the absence of collagen. Interacts (tyrosine phosphorylated) with SHC1. Interacts with SRC. Interacts with MYH9. Interacts with CDH1. Interacts with PTPN11. Interacts with NCK2 (By similarity).|||Membrane|||Mice are born at the expected Mendelian rate, but female mice are dwarfs and most of them are unable to bear offspring, due to defects in blastocyte implantation in the uterus. About one fifth can bear offspring, but for these the mammary gland fails to undergo proper differentiation during pregnancy, with hyperproliferation and abnormal branching of the mammary ducts, leading to a lactation defect. In addition, mice exhibit hearing loss, due to alterations of the inner ear. Mice display poor calcification of the fibula. They also exhibit defects in the structure of the slit diaphragm in kidney glomeruli, leading to proteinuria, but do not show overt signs of kidney dysfunction.|||Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing, but also tumor cell invasion. Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Phosphorylates PTPN11 (By similarity). Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing. http://togogenome.org/gene/10090:Lcn2 ^@ http://purl.uniprot.org/uniprot/P11672 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Cytoplasmic granule lumen|||Cytoplasmic vesicle lumen|||Expressed in the cortical tubules of the kidney (at protein level) (PubMed:30418175). Also expressed in the medullary tubules of the kidney (PubMed:30418175). Detected in lung, spleen, uterus, vagina and epididymis (PubMed:8687399).|||Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413). Binds iron through association with 2,3-dihydroxybenzoic acid (2,3-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity; limits bacterial proliferation by sequestering iron bound to microbial siderophores, such as enterobactin (PubMed:15531878, PubMed:16446425). Can also bind siderophores from M.tuberculosis (By similarity).|||Mice are normal with no visible phenotype. They however show an increased susceptibility to bacterial infections. Neutrophils show significantly less bacteriostatic activity.|||Monomer. Homodimer; disulfide-linked. Heterodimer; disulfide-linked with MMP9.|||N-glycosylated.|||Secreted|||Upon Toll-like receptor (TLRs) stimuli (PubMed:15531878). By SV-40 (PubMed:15531878). By insulin (PubMed:30418175). http://togogenome.org/gene/10090:Arpc4 ^@ http://purl.uniprot.org/uniprot/E9PWA7|||http://purl.uniprot.org/uniprot/P59999|||http://purl.uniprot.org/uniprot/Q3TX55 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Belongs to the ARPC4 family.|||Cell projection|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Aacs ^@ http://purl.uniprot.org/uniprot/Q9D2R0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Converts acetoacetate to acetoacetyl-CoA in the cytosol (By similarity). Ketone body-utilizing enzyme, responsible for the synthesis of cholesterol and fatty acids (PubMed:22985732).|||cytosol http://togogenome.org/gene/10090:Pgm2l1 ^@ http://purl.uniprot.org/uniprot/Q8CAA7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phosphohexose mutase family.|||Expressed at highest levels in the brain and testis, at intermediate levels in thymus, spleen, lung and skeletal muscle, and at lowest levels in kidney, liver and heart.|||Glucose 1,6-bisphosphate synthase using 1,3-bisphosphoglycerate as a phosphate donor and a series of 1-phosphate sugars, including glucose 1-phosphate, mannose 1-phosphate, ribose 1-phosphate and deoxyribose 1-phosphate, as acceptors. In vitro, also exhibits very low phosphopentomutase and phosphoglucomutase activity which are most probably not physiologically relevant.|||cytosol http://togogenome.org/gene/10090:Npas3 ^@ http://purl.uniprot.org/uniprot/F8VQB2 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Heatr9 ^@ http://purl.uniprot.org/uniprot/Q5QNV8 ^@ Caution ^@ Despite its name, the presence of HEAT repeat is unsure and is not confirmed by repeat-detection programs. http://togogenome.org/gene/10090:Arrdc2 ^@ http://purl.uniprot.org/uniprot/Q9D668 ^@ Similarity|||Subunit ^@ Belongs to the arrestin family.|||Interacts with WWP1 (via WW domains). http://togogenome.org/gene/10090:Or5be3 ^@ http://purl.uniprot.org/uniprot/Q7TR58 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or2n1e ^@ http://purl.uniprot.org/uniprot/Q7TRI7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or8k33 ^@ http://purl.uniprot.org/uniprot/Q7TR67 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trpc3 ^@ http://purl.uniprot.org/uniprot/Q8BNT8|||http://purl.uniprot.org/uniprot/Q8CCQ1|||http://purl.uniprot.org/uniprot/Q9QZC1 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in brain. Concentrated in cerebellar Purkinje cells and sparsely localized in cerebellar granule lyer, pontine nuclei and thalamus. Lower levels detected in other tissues.|||Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C. Activated by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May be activated by internal calcium store depletion. Inhibited by intracellular Ca(2+).|||Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC3 sub-subfamily.|||Cell membrane|||Forms a receptor-activated non-selective calcium permeant cation channel. May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors.|||Homotetramer. Interacts with ITPR1, ITPR3, MX1 and RNF24. Interacts with JPH2; the interaction is involved in maintaining Ca(2+) homeostasis in skeletal muscle and is mediated by JPH2 'Ser-165' phosphorylation.|||Membrane|||The cytoplasmic portion of the protein is required for channel assembly and gating. http://togogenome.org/gene/10090:Igf2bp1 ^@ http://purl.uniprot.org/uniprot/O88477 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM IMP/VICKZ family.|||Can form homodimers and heterodimers with IGF2BP1 and IGF2BP3 (By similarity). Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (By similarity). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 (By similarity). Associates with mRNP complex (By similarity). Interacts with FMR1 (By similarity). Component of a multisubunit autoregulatory RNP complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Interacts with AGO1 and AGO2 (By similarity). Interacts, through domains KH3 and KH4, with PABPC1 in an RNA-independent manner (By similarity). Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Interacts with ELAVL4 in an RNA-dependent manner. Associates with microtubules and polysomes. Interacts with ELAVL1 and MATR3 (By similarity).|||Cytoplasm|||Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full-length protein.|||Expressed during embryonic development and expression declines towards birth (at protein level). At 10.5 dpc, mainly expressed in the fore- and hindbrain, the snout, the branchial arches, the developing limb buds, and the tail. At 12.5 dpc, expression increased in the expanding fore- and hindbrain, as well as in the neural tract. Marked expression also observed in the snout, the interdigital mesenchyme of the limb buds, the tail, the branchial arches and somites, and the developing eye, tongue, heart and liver. Expressed in myoblasts and myotubes at 12.5 dpc (at protein level). From 12.5 to 15.5 dpc, expressed at the basal plasma cell membrane in the basal layer of the epidermis of the skin, lung and intestine (at protein level). Expressed in gonads at 12.5 and 14.5 dpc (at protein level). At 14.5 dpc in limb buds, becomes restricted to the future tendons. Expressed in germ cells at 16.5 dpc (at protein level). At 17.5 dpc, expression generally decreases, but remains high in the intestine, in the developing tubules of the kidney, and in the liver. Expressed until P12, although very low levels may remain in some tissues, such as intestines, kidney and brain, throughout adulthood. Following colonic injury, up-regulated in the wound mucosa at days 2 and 4 post-injury and down-regulated at day 6 post-injury, as compared with uninjured mucosa.|||Expressed in zygotes and blastocysts (at protein level). Expressed in brain, skeletal muscle, trophoblasts of placenta, oocytes and spermatogonia (at protein level). Expressed in testis and ovary. Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level).|||Mutant mice exhibit high perinatal mortality and only 50% are alive 3 days after birth. Early death may be due to intestinal dysfunction. Animals are on average 40% smaller than wild-type and heterozygous sex-matched littermates. Growth retardation, probably due to hypoplasia, appears from 17.5 dpc and remains permanent into adult life. Mutant animals exhibit other stricking features, including impaired development of the intestine, with small and misshapen villi and twisted colon crypts, abnormal kidney architecture and loss of cartilage in the lower extremities. Some animals show signs of neurological damage, including aggressive behavior, restlessness and circular movements.|||Nucleus|||P-body|||Phosphorylated. Phosphorylation may impair association with ACTB mRNA and hence abolishes translational repression (By similarity).|||RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (By similarity). Regulates localized beta-actin/ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The RNP thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, prevents ACTB mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. Monomeric ACTB then assembles into the subcortical actin cytoskeleton (By similarity). During neuronal development, key regulator of neurite outgrowth, growth cone guidance and neuronal cell migration, presumably through the spatiotemporal fine tuning of protein synthesis, such as that of ACTB (By similarity). May regulate mRNA transport to activated synapses (By similarity). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells (By similarity). Binds to the oncofetal H19 transcript and regulates its localization (By similarity). Binds to and stabilizes BTRC/FBW1A mRNA (By similarity). Binds to the adenine-rich autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent interaction with AGO2 (By similarity). During cellular stress, such as oxidative stress or heat shock, stabilizes target mRNAs that are recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts (By similarity). Interacts with GAP43 transcript and transports it to axons. Binds to the 3'-UTR of IGF2 mRNA by a mechanism of cooperative and sequential dimerization and regulates IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA, in the coding region instability determinant (CRD) of the open reading frame (ORF), hence prevents MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD. Binding to MYC mRNA is enhanced by m6A-modification of the CRD (By similarity). Binds to and stabilizes ABCB1/MDR-1 mRNA. Binds to the neuron-specific TAU mRNA and regulates its localization. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons. During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing.|||Stress granule|||axon|||dendrite|||dendritic spine|||filopodium|||growth cone|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Kcnj8 ^@ http://purl.uniprot.org/uniprot/A0A0J9YMM3|||http://purl.uniprot.org/uniprot/P97794|||http://purl.uniprot.org/uniprot/Q3U118 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ8 subfamily.|||Membrane|||This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium (By similarity). http://togogenome.org/gene/10090:Cfap68 ^@ http://purl.uniprot.org/uniprot/Q9D131 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CFAP68 family.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||Nucleus|||cilium axoneme http://togogenome.org/gene/10090:Kcns2 ^@ http://purl.uniprot.org/uniprot/O35174|||http://purl.uniprot.org/uniprot/Q69ZQ8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. S (TC 1.A.1.2) subfamily. Kv9.2/KCNS2 sub-subfamily.|||Cell membrane|||Detected in brain, but not in the other tissues tested. Expression was highest in the olfactory bulb, cerebral cortex, hippocampus, habenula, basolateral amygdaloid nuclei and cerebellum (PubMed:9305895).|||Heterotetramer with KCNB1 and KCNB2 (PubMed:9305895). Does not form homomultimers (PubMed:9305895).|||Membrane|||Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1 and KCNB2; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 and KCNB2 (PubMed:9305895).|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. http://togogenome.org/gene/10090:Pacc1 ^@ http://purl.uniprot.org/uniprot/Q9D771 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the proton-activated chloride channel family.|||Cell membrane|||Mice are viable and appear mostly normal (PubMed:31023925). Cortical neurons completely lack proton-activated chloride channel activity (PubMed:31023925). Neurons are partially but significantly protected from delayed cell death induced by 1-hour acid treatment (PubMed:31023925).|||Proton-activated chloride channel that mediates import of chloride ion in response to extracellular acidic pH (PubMed:31023925). Involved in acidosis-induced cell death by mediating chloride influx and subsequent cell swelling (PubMed:31023925). http://togogenome.org/gene/10090:Inka1 ^@ http://purl.uniprot.org/uniprot/Q9CX62 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the INKA family.|||Contains 2 Inka boxes (also named iBox or inca box). The Inka boxes bind and inhibit PAK4 by binding a substrate-like manner.|||Cytoplasm|||Expressed in the cephalic mesenchyme, heart and paraxial mesoderm prior to 8.5 dpc. Expression is then observed in the migratory neural crest cells and their derivatives. As development progresses, expression is also observed in the limb buds and perichondrial tissue.|||Expressed in tissues of the developing head during neurulation.|||Expression of Inka1 is not regulated by AP-2-alpha/Tfap2a, as it is the case for orthologous protein in zebrafish and Xenopus.|||Inhibitor of the serine/threonine-protein kinase PAK4. Acts by binding PAK4 in a substrate-like manner, inhibiting the protein kinase activity.|||Interacts with PAK4 (PubMed:17314132).|||No visible phenotype in most cases: most mice are viable and fertile. A low percentage of mice show exencephaly.|||Nucleus http://togogenome.org/gene/10090:Tmem234 ^@ http://purl.uniprot.org/uniprot/Q8R1E7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM234 family.|||Membrane http://togogenome.org/gene/10090:Tmco5b ^@ http://purl.uniprot.org/uniprot/Q80X59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMCO5 family.|||Membrane http://togogenome.org/gene/10090:Abcc5 ^@ http://purl.uniprot.org/uniprot/Q9R1X5 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites like cyclic nucleotides, such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) (By similarity) (PubMed:17229149). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers resistance to the antiviral agent PMEA (By similarity). Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity (By similarity). Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (PubMed:31338999).|||Although other labs have confirmed the ability of ABCC5 to transport cGMP in an ATP-dependent manner, they obtained a much lower affinity for this substrate (By similarity) (PubMed:17229149). The authors conclude that ABCC5 is a low-affinity cyclic nucleotide transporter and a major function in cGMP excretion is unlikely (By similarity) (PubMed:17229149).|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Cytoplasmic granule|||Detected in brain endothelial cells.|||Endosome membrane|||Golgi apparatus lumen|||Mrp5 knockout mice are viable with no overt phenotypes, deficient mice accumulate endogenous glutamate conjugates in several tissues, including the inhibitory neuropeptides N-acetylaspartylglutamate (NAAG) and N-acetylaspartyldiglutamate (NAAG2), but brain in particular (PubMed:26515061). Abcc5-/- mice show lower white and brown adipose tissue and increased glucagon-like peptide 1 (GLP-1) release from enteroendocrine cells of the small intestine, and are more insulin sensitive (PubMed:31338999). http://togogenome.org/gene/10090:Or12e10 ^@ http://purl.uniprot.org/uniprot/A2AVC7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Atxn7 ^@ http://purl.uniprot.org/uniprot/Q8R4I1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ataxin-7 family.|||Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP, TAF9 and ATXN7. The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22. Interacts with SORBS1, PSMC1 and CRX. Interacts with TRRAP, GCN5L2 and TAF10 (By similarity). Interacts with alpha tubulin (By similarity).|||Involved in neurodegeneration. Acts as component of the STAGA transcription coactivator-HAT complex. Mediates the interaction of STAGA complex with the CRX and is involved in CRX-dependent gene activation (By similarity). Necessary for microtubule cytoskeleton stabilization (By similarity).|||Nucleus|||Nucleus matrix|||Proteolytically cleaved by caspase-7 (CASP7).|||Sumoylation has no effect on subcellular location or interaction with components of the STAGA complex.|||Widely expressed in adult tissues, with the highest expression in heart, brain, liver and kidney.|||cytoskeleton|||nucleolus http://togogenome.org/gene/10090:Cdhr3 ^@ http://purl.uniprot.org/uniprot/Q8BL00 ^@ Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.|||Cell membrane http://togogenome.org/gene/10090:Tmem130 ^@ http://purl.uniprot.org/uniprot/Q6NXM3 ^@ Subcellular Location Annotation ^@ Golgi apparatus membrane http://togogenome.org/gene/10090:Arhgap8 ^@ http://purl.uniprot.org/uniprot/Q9CXP4 ^@ Function|||Tissue Specificity ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.|||Highly expressed in skeletal muscle, lung and testis, and at lower levels in kidney, stomach and colon. Not detected in heart, liver, spleen, breast, brain, neonatal head or pancreas. http://togogenome.org/gene/10090:Arid3b ^@ http://purl.uniprot.org/uniprot/Q9Z1N7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Embryos die before 11.5 dpc and display various abnormalities, including wavy neural tube, small branchial arches and defects of cardiovascular system.|||Expressed at high levels in testis. Also expressed in prostate, thyroid and thymus.|||First detected at 7 dpc. Strongly expressed in cranial mesenchyme and caudal mesoderm. Expression in cranial mesenchyme decreases starting from 10.5 dpc.|||Heterodimer with ARID3A. Interacts with unphosphorylated RB1 (By similarity).|||Nucleus|||Transcription factor involved in the production of cranial mesenchymal tissues. Favors nuclear targeting of ARID3A. http://togogenome.org/gene/10090:Actl11 ^@ http://purl.uniprot.org/uniprot/Q9D5V1 ^@ Similarity ^@ Belongs to the actin family. http://togogenome.org/gene/10090:Cnmd ^@ http://purl.uniprot.org/uniprot/G5E8Z6|||http://purl.uniprot.org/uniprot/Q9Z1F6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ After cleavage, the post-translationally modified ChM-I is secreted as a glycoprotein.|||Aged mice show enhanced VEGFA expression, angiogenesis, inflammatory cell infiltration, aortic stenosis, lipid deposition and calcification in the cardiac valves.|||Belongs to the chondromodulin-1 family.|||Bifunctional growth regulator that stimulates the growth of cultured chondrocytes in the presence of basic fibroblast growth factor (FGF) but inhibits the growth of cultured vascular endothelial cells. May contribute to the rapid growth of cartilage and vascular invasion prior to the replacement of cartilage by bone during endochondral bone development (By similarity). Inhibits in vitro tube formation and mobilization of endothelial cells (By similarity). Plays a role as antiangiogenic factor in cardiac valves to suppress neovascularization.|||Detected from 9.5 dpc in the cardiac valve precursor cells from the atrioventricular cushions and outflow. At 10 dpc expressed in the cardiac jelly covering the trabeculating cardiomyocytes of the left ventricle, the outer curvature of the right ventricle and the outflow tract. Expression in the ventricles decreased gradually as development progressed, and disappeared by mid-embryogenesis (at protein level).|||Detected in the four cardiac valves, valvular interstitial cells and extracellular matrix (at protein level).|||Endomembrane system|||extracellular matrix http://togogenome.org/gene/10090:H2al1o ^@ http://purl.uniprot.org/uniprot/L7MU04 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Arid3a ^@ http://purl.uniprot.org/uniprot/A0A0R4J1A7|||http://purl.uniprot.org/uniprot/Q62431 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ B-cell specific in the adult. Expressed in B-cell progenitors, down-regulated in the immature B-cell stage, and is up-regulated again at later stages of B-lymphocyte differentiation.|||Cytoplasm|||Expressed in lymphocytes from fetal liver. Expressed in fetal thymus and brain.|||Homodimer.|||Homodimer. Heterodimer with ARID3B. Interacts with E2F1 (By similarity). Interacts with GTF2I and BTK.|||Nucleus|||Transcription factor involved in B-cell differentiation. Binds a VH promoter proximal site necessary for induced mu-heavy-chain transcription. Binds the minor groove of a restricted ATC sequence that is sufficient for nuclear matrix association. This sequence motif is present in matrix-associating regions (MARS) proximal to the promoter and flanking E mu. Activates E mu-driven transcription by binding these sites. May be involved in the control of cell cycle progression by the RB1/E2F1 pathway.|||Transcription factor. http://togogenome.org/gene/10090:Rxrg ^@ http://purl.uniprot.org/uniprot/E9Q9V9|||http://purl.uniprot.org/uniprot/P28705 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by EP300.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Expressed from embryo day 10.5 to birth. At day 10-13, expression in somites and the ventral horns of the spinal chord. At day 13.5, strongly expressed in the corpus striatum. At day 16.5, expression also in the pituitary with weaker expression in the neck, skeletal muscle and tongue. Expression in the corpus striatum continues until at least 7 days after birth.|||Homodimer (By similarity). Heterodimer with a RAR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Interacts with RARA (By similarity).|||Knockout mice exhibit memory deficits.|||Nucleus|||Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity). http://togogenome.org/gene/10090:Vmn1r86 ^@ http://purl.uniprot.org/uniprot/L7N213 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cenpq ^@ http://purl.uniprot.org/uniprot/A0A1I7Q4A6|||http://purl.uniprot.org/uniprot/Q9CPQ5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-Q/OKP1 family.|||Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Plays an important role in chromosome congression and in the recruitment of CENP-O complex (which comprises CENPO, CENPP, CENPQ and CENPU), CENPE and PLK1 to the kinetochores.|||Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU.|||Nucleus|||Phosphorylation at Ser-49 is essential for CENPE recruitment to kinetochores and orderly chromosome congression.|||centromere http://togogenome.org/gene/10090:Insrr ^@ http://purl.uniprot.org/uniprot/Q9WTL4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues between pH 7.9 and pH 10.5.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Highly expressed in the islets as well as in pancreatic beta-cells.|||Membrane|||Probable tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain (By similarity).|||Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB.|||Renal function is impaired, with reduced ability of the collecting duct to adapt to alkalosis.|||The extracellular domain is required for sensing alterations in external pH. http://togogenome.org/gene/10090:Gm10230 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Castor1 ^@ http://purl.uniprot.org/uniprot/Q9CWQ8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Based on x-ray crystallography data, the protein would be constituted of 4 tandem ACT domains instead of the 2 predicted from the sequence.|||Belongs to the GATS family.|||Forms homodimers and heterodimers with CASTOR2 (By similarity). Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by arginine (By similarity). Interacts with TM4SF5; the interaction is positively regulated by leucine and is negatively regulated by arginine (By similarity).|||Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway. As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1. Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1-containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway.|||Phosphorylation at Ser-14 by AKT1, promoting the interaction between CASTOR1 and RNF167.|||Ubiquitinated by RNF167 via 'Lys-29'-polyubiquitination, leading to its degradation, releasing the GATOR2 complex. Ubiquitination by RNF167 is promoted by phosphorylation at Ser-14 by AKT1.|||cytosol http://togogenome.org/gene/10090:Cobll1 ^@ http://purl.uniprot.org/uniprot/Q3UMF0 ^@ Tissue Specificity ^@ Detected in embryonic first branchial arc, branchial clefts and limb buds. http://togogenome.org/gene/10090:Vmn1r184 ^@ http://purl.uniprot.org/uniprot/E9Q2N4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arpp19 ^@ http://purl.uniprot.org/uniprot/E9Q827|||http://purl.uniprot.org/uniprot/P56212 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the endosulfine family.|||Cytoplasm|||Interacts (when phosphorylated at Ser-62) with PPP2R2D. Interacts with SNCA (By similarity).|||Isoform ARPP-19 is highly expressed in the embryo and its levels decrease progressively as development proceeds. In contrast, isoform ARPP-16 appears in the brain at the end of the first postnatal week and increases to reach a plateau.|||Phosphorylation at Ser-62 by GWL during mitosis is essential for interaction with PPP2R2D (PR55-delta) and subsequent inactivation of PP2A (By similarity). Phosphorylated by PKA.|||Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis.|||Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-62 during mitosis, specifically interacts with PPP2R2D (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase. May indirectly enhance GAP-43 expression by binding to the NGF-regulatory region of its mRNA (By similarity). http://togogenome.org/gene/10090:Cybc1 ^@ http://purl.uniprot.org/uniprot/Q3TYS2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CYBC1 family.|||Endoplasmic reticulum membrane|||Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer (By similarity). Controls the phagocyte respiratory burst and is essential for innate immunity (PubMed:28351984).|||Interacts with CYBB; CYBC1 may act as a chaperone stabilizing Cytochrome b-245 heterodimer.|||Mutants are highly susceptible to Salmonella and Listeria infection and are impaired in their ability to control replication of either pathogen (PubMed:28351984). Mutant neutrophiles have a highly impaired superoxide burst (PubMed:28351984). Mice are very susceptible to Listeria monocytogenes and die within 5 days of infection, fail to form neutrophil extracellular traps but are resistant to melanoma metastasis (PubMed:28351984). http://togogenome.org/gene/10090:Zyg11a ^@ http://purl.uniprot.org/uniprot/A0A1Y7VNL1|||http://purl.uniprot.org/uniprot/A0A217FL76 ^@ Similarity ^@ Belongs to the zyg-11 family. http://togogenome.org/gene/10090:Gdf15 ^@ http://purl.uniprot.org/uniprot/Q9Z0J7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 3 (P3), detected in heart and plasma, expression decreases with lower levels at P7 to, at least, P13.|||Belongs to the TGF-beta family.|||Expression is up-regulated by obesity.|||Highly expressed in liver (PubMed:10779363, PubMed:28572090, PubMed:29046435). Detected in plasma (at protein level) (PubMed:28572090, PubMed:29046435). Expressed by cardiomyocytes, expression is highly increased in heart diseases (PubMed:28572090). Also detected in subcutaneous fat (PubMed:28572090, PubMed:29046435).|||Homodimer; disulfide-linked (By similarity). Interacts with GFRAL; ligand of GFRAL which mediates GDF15 internalization and cellular signaling through interaction with RET (PubMed:28846098, PubMed:28846099).|||Mutants weight more, have increases adiposity associated with increased spontaneous food intake and exhibit reduced basal energy expenditure and physical activity (PubMed:23468844). Female mutants exhibit some additional alterations in reduced basal energy expenditure and physical activity (PubMed:23468844). At behavioral level, they exhibit a task-dependent increase in locomotion and exploration and reduced anxiety-related behaviors across tests. Their spatial working memory and social behaviors are not affected. They form an increased association with conditioned stimulus in fear conditioning testing and also display significantly improved prepulse inhibition (PubMed:28081177).|||Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses. Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem. It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which constitutes part of the 'emergency circuit' that shapes feeding responses to stressful conditions (PubMed:28953886, PubMed:28846097, PubMed:28846099, PubMed:28572090, PubMed:23468844, PubMed:29046435). On hepatocytes, inhibits growth hormone signaling (PubMed:28572090).|||Secreted http://togogenome.org/gene/10090:Dgkg ^@ http://purl.uniprot.org/uniprot/Q570Z5|||http://purl.uniprot.org/uniprot/Q8C413|||http://purl.uniprot.org/uniprot/Q91WG7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:32033984). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:32033984). Has no apparent specificity with regard to the acyl compositions of diacylglycerol (By similarity). Specifically expressed in the cerebellum where it controls the level of diacylglycerol which in turn regulates the activity of protein kinase C gamma (PubMed:32033984). Through protein kinase C gamma, indirectly regulates the dendritic development of Purkinje cells, cerebellar long term depression and ultimately cerebellar motor coordination (PubMed:32033984).|||Expressed in hippocampus and cerebellar Purkinje cells and weakly and diffusely expressed in the granule cells.|||Homozygous knockout mice show impairments in motor coordination, long-term depression/LTD and development of Purkinje cells (PubMed:32033984). The level of phosphatidic acid in synaptosomal membranes is significantly decreased (PubMed:32033984). The number of branches, the total length of the dendrites and the membrane capacitance of the distal dendritic region are significantly lower (PubMed:32033984).|||Membrane|||The activity is calcium-dependent (By similarity). Requires phosphatidylserine for maximal activity (By similarity).|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Abi3 ^@ http://purl.uniprot.org/uniprot/Q8BYZ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ABI family.|||Cytoplasm|||Inhibits ectopic tumor cell metastasis of SRD cells. In vitro, reduces cell motility.|||May interact with PAK1 and PAK2. Probably interacts with TARSH (By similarity). http://togogenome.org/gene/10090:Cep55 ^@ http://purl.uniprot.org/uniprot/Q8BT07 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cleavage furrow|||Cytoplasm|||Homodimer. Interacts (phosphorylated on Ser-423 and Ser-426) with PLK1. Interacts with AKAP9/CG-NAP; the interaction occurs in interphase and is lost upon mitotic entry. Interacts with PCNT/Kendrin; the interaction occurs in interphase and is lost upon mitotic entry. Directly interacts with PDCD6IP; this interaction is required for PDCD6IP targeting to the midbody; CEP55 binds PDCD6IP in a 2:1 stoichiometry; PDCD6IP competes with TSG101 for the same binding site. Interacts with TSG101; TSG101 competes with PDCD6IP for the same binding site; interaction is required for cytokinesis. Interacts with MVB12A, VPS37B, VPS37C and VPS28 (By similarity).|||Midbody ring|||Plays a role in mitotic exit and cytokinesis. Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis. Not required for microtubule nucleation. Plays a role in the development of the brain and kidney.|||There is a hierachy of phosphorylation, where both Ser-423 and Ser-426 are phosphorylated at the onset of mitosis, prior to Ser-434. Phosphorylation at Ser-423 and Ser-426 is required for dissociation from the centrosome at the G2/M boundary. Phosphorylation at the 3 sites, Ser-423, Ser-426 and Ser-434, is required for protein function at the final stages of cell division to complete cytokinesis successfully (By similarity).|||centriole|||centrosome http://togogenome.org/gene/10090:Cpa5 ^@ http://purl.uniprot.org/uniprot/B2RQW9|||http://purl.uniprot.org/uniprot/Q8R4H4 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Detected in testis germ cells.|||Secreted http://togogenome.org/gene/10090:Krt18 ^@ http://purl.uniprot.org/uniprot/P05784 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||By retinoic acid and IL-6.|||Cytoplasm|||During embryogenesis, expressed in a complex spatial and temporal pattern in various embryonic epithelia. In 7.5 and 13.5 day old embryo, expressed in most endodermal epithelia, ectodermal and nascent mesodermal tissues. When the neural plate forms, expression begins in the cells of skin ectoderm, head process/notochord, periderm, whisker buds, choroid plexus and the epithelia of auditory duct and inner ear. High expression in the lining endodermal cells when the foregut and hindgut invaginations form. Expression in all three layers of the urothelium starts at day 15 in the embryo and is not visible after day 18. By day 11 and 12, the entire embryonic palatal epithelium shows expression as well as the nasal passages and the roof of the mouth; which disappears progresively from day 13 to 15.|||Expressed in endoderm, intestinal epithelial cells and in most extraembryonic tissues.|||Heterotetramer of two type I and two type II keratins. KRT18 associates with KRT8 (PubMed:24940650). Interacts with PLEC isoform 1C, when in a heterodimer with KRT8 (PubMed:24940650). Interacts with PNN and mutated CFTR. Interacts with YWHAE, YWHAH and YWHAZ only when phosphorylated. Interacts with the thrombin-antithrombin complex. Interacts with DNAJB6, TCHP and TRADD (By similarity). Interacts with FAM83H (By similarity). Interacts with EPPK1 (PubMed:25617501). Interacts with PKP1 and PKP2 (By similarity).|||Nucleus matrix|||O-GlcNAcylation increases solubility, and decreases stability by inducing proteasomal degradation.|||Phosphorylation increases by IL-6.|||Proteolytically cleaved by caspases during epithelial cell apoptosis. Cleavage occurs at Asp-231 by either caspase-3, caspas-6 or caspase-7.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection.|||nucleolus|||perinuclear region http://togogenome.org/gene/10090:Zcchc8 ^@ http://purl.uniprot.org/uniprot/Q9CYA6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZCCHC8 family.|||Component of a nuclear TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes. Identified in the spliceosome C complex. Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation. Interacts with proteins involved in RNA processing and degradation such as MTREX and RBM7; interaction with MTREX enhances MTREX RNA helicase activity and bridges between RBM7 and MTREX. Interacts with TERC, the telomerase RNA component.|||Phosphorylation at Thr-495 by GSK3 is triggered in cells entering mitosis.|||Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs. NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. May be involved in pre-mRNA splicing. It is required for 3'-end maturation of telomerase RNA component (TERC), TERC 3'-end targeting to the nuclear RNA exosome, and for telomerase function.|||The C-terminal part (659-707) contributes to MTREX RNA helicase activity, in part, by enhancing its RNA-dependent ATPase activity.|||ZCCHC8-null mice have a small brain volume, cranial deformities with domed-shaped heads, and severe hydrocephalus with ventriculomegaly. Defective turnover of low abundance RNA polymerase II transcripts is detected in developing brain of knockout animals.|||nucleoplasm http://togogenome.org/gene/10090:Krt16 ^@ http://purl.uniprot.org/uniprot/Q3SYP5|||http://purl.uniprot.org/uniprot/Q3ZAW8|||http://purl.uniprot.org/uniprot/Q9Z2K1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||During embryonic development, initially localizes within early hair germs, but rapidly shifts to a subset of cells at the interface of basal and suprabasal cells above and around the hair germ (PubMed:12445204). Expressed in hair follicles and in most cells in the spinous layer at birth (PubMed:11408584).|||Epidermis-specific type I keratin that plays a key role in skin (PubMed:22336941, PubMed:24218583). Acts as a regulator of innate immunity in response to skin barrier breach: required for some inflammatory checkpoint for the skin barrier maintenance (PubMed:24218583).|||Expressed in the epithelia of the tongue, upper and lower palate, footpad, proximal nail fold and nail bed, penile spine, sweat gland ducts, and back epidermis (at protein level) (PubMed:12445204). Expressed in upper suprabasal layers of the corneal epithelium (at protein level) (PubMed:26758872). Expressed in internal stratified epithelia in the esophagus and vagina (at protein level) (PubMed:12445204). Expressed in transitional stratified squamous epithelia in the forestomach, anal canal, and nasal cavity (at protein level) (PubMed:12445204). Expressed in transitional epithelia of the ureter, bladder and urethra (at protein level) (PubMed:12445204). In mature hair follicles, expressed in the companion layer of the outer root sheath during anagen and in the club hair sheath during catagen and telogen (at protein level) (PubMed:12445204).|||Heterodimer of a type I and a type II keratin. KRT16 associates with KRT6 isomers (KRT6A or KRT6B) (PubMed:8636216). Interacts with TCHP (By similarity). Interacts with TRADD (PubMed:16702408).|||In response to epidermal stress such as wounding.|||Mice were born alive at approximately Mendelian ratios but increased postnatal mortality is observed. Surviving mice show oral lesions as well as palmoplantar keratoderma-like hyperkeratotic calluses on front and hind paws, which impair the ability to walk.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Naa38 ^@ http://purl.uniprot.org/uniprot/Q9D2U5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues.|||Belongs to the snRNP Sm proteins family.|||Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Ephx2 ^@ http://purl.uniprot.org/uniprot/P34914 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.|||Bifunctional enzyme. The C-terminal domain has epoxide hydrolase activity and acts on epoxides (alkene oxides, oxiranes) and arene oxides (PubMed:7840649, PubMed:21217101). Plays a role in xenobiotic metabolism by degrading potentially toxic epoxides (By similarity). Also determines steady-state levels of physiological mediators (By similarity).|||Bifunctional enzyme. The N-terminal domain has lipid phosphatase activity, with the highest activity towards threo-9,10-phosphonooxy-hydroxy-octadecanoic acid, followed by erythro-9,10-phosphonooxy-hydroxy-octadecanoic acid, 12-phosphonooxy-octadec-9Z-enoic acid and 12-phosphonooxy-octadec-9E-enoic acid (By similarity). Has phosphatase activity toward lyso-glycerophospholipids with also some lower activity toward lysolipids of sphingolipid and isoprenoid phosphates (By similarity).|||Cytoplasm|||Detected in liver, intestine, ovary and kidney. Detected at low levels in heart and muscle.|||Homodimer.|||In knockout mice, hepoxilin turnover to trioxilins is greatly abolished (PubMed:21217101). In livers, the activity toward HxA3 (8-hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate) and HxB3 (10-hydroxy-(11S,12S)-epoxy- (5Z,8Z,14Z)-eicosatrienoate) is greatly reduced compared with the WT mice (PubMed:21217101).|||Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU), N-adamantyl-N[']-cyclohexyl urea (ACU), 4-(((1S, 4S)-4-(3-((3S, 5S, 7S)-adamantan-1-yl) ureido)cyclohexyl)oxy)benzoic acid (c-AUCB), 4-(((1R, 4R)-4-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido)cyclohexyl)oxy)benzoic acid (t-AUCB), 4-(((1R, 4R)-4-(3-(4(trifluoromethoxy)phenyl)ureido)cyclohexyl)oxy)benzoic acid (t-TAUCB) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA) (By similarity). Phosphatase activity is inhibited by dodecyl-phosphate, phospholipids such as phospho-lysophosphatidic acids and fatty acids such as palmitic acid and lauric acid (PubMed:21217101).|||Peroxisome|||The N-terminal domain has phosphatase activity. The C-terminal domain has epoxide hydrolase activity.|||The N-terminus is blocked.|||The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation (By similarity).|||Up-regulated during the luteal phase of the stimulated estrus cycle and by compounds that cause peroxisome proliferation, such as clofibrate, tiadenol and fenofibrate. http://togogenome.org/gene/10090:Zfp36l3 ^@ http://purl.uniprot.org/uniprot/Q5ISE2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Contains long series of C-terminal alanine-rich repeats that serve to maintain the protein in the cytoplasm.|||Cytoplasm|||Expressed in placenta and extraembryonic tissues (at protein level). Not detected in embryos and fetus (PubMed:15814898, PubMed:26952984).|||Expressed in placenta at 14.5 dpc. Expressed in the single layer of endodermal epithelial cells of the visceral yolk sac at 15.5 dpc (PubMed:26952984). Expressed in syncytiotrophoblast and trophoblast giant cells of the labyrinth region of the placenta at 17.5 dpc (PubMed:15814898, PubMed:26952984) (at protein level). Expressed specifically in extraembryonic structures, in placenta from 9.5 to 18.5 and yolk sac/amnion from 12.5 to 18.5 (PubMed:15814898, PubMed:26952984). Expressed in the labyrinthine layer of the trophoblastic placenta at 10.5, 12.5 and 14.5 dpc (PubMed:15814898). Expressed in syncytiotrophoblast and trophoblast giant cells, less in spongiotrophoblast cells, and not detected in maternal decidua or in allantois at 17.5 dpc (PubMed:26952984).|||Membrane|||Mice are viable and fertile, without apparent morphological or histological abnormalities in the placenta, but display a decrease in the numbers of surviving offspring. Display an abnormal accumulation of placental 3'UTR ARE-containing mRNAs. Exhibit also a decrease in ARE-containing mRNA decay in differentiated trophoblast stem cells.|||Placenta-specific zinc-finger RNA-binding protein that destabilizes cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:15814898, PubMed:26952984). Binds to the 3'-UTR ARE of placental target mRNAs, such as TNF, HBEGF and LIPG (PubMed:15814898, PubMed:18367448, PubMed:26952984). Involved in placental expression of many genes important for normal placental physiology (PubMed:26952984).|||Rodent-specific retrogene derived apparently from its related family member ZFP36L2 mRNA (PubMed:15814898, PubMed:26493225). http://togogenome.org/gene/10090:Mei4 ^@ http://purl.uniprot.org/uniprot/Q8BRM6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MEI4L family.|||Chromosome|||Deficient DNA double-strand break formation during meiotic recombination.|||Expressed in adult testis and brain and in embryonic ovary.|||In the testis, expression is detected at 4 days postpartum (dpp) with a peak between days 10 and 14. Levels decrease by 18 dpp with a further decrease in the adult.|||Interacts with REC114 (PubMed:20551173). Part of the MCD recombinosome complex, at least composed of IHO1, REC114 and MEI4 (PubMed:27723721).|||Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination (PubMed:20551173, PubMed:25795304, PubMed:27723721). Probably acts by forming a complex with IHO1 and REC114, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis (PubMed:27723721). http://togogenome.org/gene/10090:Neil2 ^@ http://purl.uniprot.org/uniprot/Q6R2P8 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-50 leads to loss of DNA nicking activity.|||Belongs to the FPG family.|||Binds EP300.|||Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Has DNA glycosylase activity towards 5-hydroxyuracil and other oxidized derivatives of cytosine with a preference for mismatched double-stranded DNA (DNA bubbles). Has low or no DNA glycosylase activity towards thymine glycol, 2-hydroxyadenine, hypoxanthine and 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates (By similarity).|||Nucleus|||The zinc-finger domain is important for DNA binding. http://togogenome.org/gene/10090:Vmn1r30 ^@ http://purl.uniprot.org/uniprot/Q8R2D2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pptc7 ^@ http://purl.uniprot.org/uniprot/Q6NVE9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Mitochondrion matrix|||Protein phosphatase which positively regulates biosynthesis of the ubiquinone, coenzyme Q (By similarity). Dephosphorylates the ubiquinone biosynthesis protein COQ7 which is likely to lead to its activation (By similarity). http://togogenome.org/gene/10090:Paqr7 ^@ http://purl.uniprot.org/uniprot/Q3TT73|||http://purl.uniprot.org/uniprot/Q80ZE4 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ADIPOR family.|||Cell membrane|||Detected in most adult tissues. Higher expression found in white fat and liver than brown fat and skeletal muscle.|||Membrane|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(i) mediated pathway. May be involved in oocyte maturation. Involved in neurosteroid inhibition of apoptosis. Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone.|||Up-regulated in PPAR gamma 1-induced adipogenic liver. http://togogenome.org/gene/10090:Plcl2 ^@ http://purl.uniprot.org/uniprot/Q8K394 ^@ Caution|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||In the PI-PLC X-box Thr-487 is present instead of the conserved His which is one of the active site residues. It is therefore expected that this protein lacks catalytic activity.|||May play an role in the regulation of Ins(1,4,5)P3 around the endoplasmic reticulum.|||Ubiquitously expressed, with a strong expression in skeletal muscle. http://togogenome.org/gene/10090:Inmt ^@ http://purl.uniprot.org/uniprot/P40936 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.|||Catalyzes the N-methylation of tryptamine and structurally related compounds (By similarity). Functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds.|||Cytoplasm|||Detected in lung and liver (at protein level).|||Inhibited by the S-adenosyl-L-methionine analog sinefungin and by the product S-adenosyl-L-homocysteine.|||Monomer.|||Was originally thought to be a thioether S-methyltransferase but appears to be the ortholog of human INMT. http://togogenome.org/gene/10090:Abcg8 ^@ http://purl.uniprot.org/uniprot/E9Q0P2|||http://purl.uniprot.org/uniprot/Q7TSR6|||http://purl.uniprot.org/uniprot/Q9DBM0 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A functional Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. The essential Lys in this region is not conserved in ABCG8 (G-S-S-G-C-R-A-S) and is not required for transport activity mediated by the heterodimer with ABCG5.|||ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:16352607, PubMed:16867993, PubMed:18402465). Plays an essential role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile (PubMed:12444248, PubMed:14504269, PubMed:14657202, PubMed:25378657). Plays an important role in preventing the accumulation of dietary plant sterols in the body (PubMed:12444248, PubMed:14657202). Required for normal sterol homeostasis (PubMed:12444248, PubMed:14657202). The heterodimer with ABCG5 has ATPase activity (PubMed:16352607, PubMed:16867993).|||Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.|||Cell membrane|||Cholesterol transport is inhibited by vanadate and by beryllium fluoride.|||Detected in liver and jejunum (at protein level) (PubMed:12444248, PubMed:18402465, PubMed:25378657). Expressed in jejunum and ileum and, at lower level, in the liver (PubMed:11907139, PubMed:11099417, PubMed:12444248, PubMed:15040800, PubMed:25378657).|||Heterodimer with ABCG5.|||Membrane|||Mice are born at the expected Mendelian rate. They display decreased cholesterol levels, but strongly increased levels of the food-derived plant sterols campesterol and beta-sitosterol in blood plasma, liver and spleen (PubMed:25378657). Besides, mutant mice may have slightly increased total plasma triglyceride levels. Expression of Abcg5 is not affected. Mutant mice display decreased biliary sterol secretion (PubMed:15040800). Mice deficient for both Abcg5 and Abcg8 appear healthy and are fertile, but display strongly increased levels of the food-derived plant sterols sitosterol and campesterol in liver and blood plasma (PubMed:12444248, PubMed:14657202, PubMed:25378657). When mice are fed chow containing 0.02% cholesterol, cholesterol levels in blood plasma and in liver are considerably lower than in wild-type (PubMed:12444248, PubMed:14657202). In spite of the increased plasma and liver levels of plant sterols, and the decreased cholesterol levels, the total sterol levels in plasma and liver are closely similar in wild-type and mutant mice (PubMed:14657202). When mice are fed chow containing 2% cholesterol, plasma cholesterol levels remain stable in wild-type, but increase 2.4-fold in mutant mice. In the liver of mice kept on chow containing 2% cholesterol, cholesterol levels increase 3-fold for wild-type mice and 18-fold for mutant mice, resulting in much higher cholesterol levels than in wild-type livers (PubMed:12444248). Dietary cholesterol absorption appears normal in mutant mice, but the absorption of dietary cholestanol, campesterol and sitosterol is increased (PubMed:12444248). At the same time, mutant mice have very low cholesterol levels in bile, suggesting that the increased hepatic cholesterol levels are due to impaired cholesterol secretion into bile (PubMed:12444248). Likewise, the levels of the food-derived plant sterols stigmasterol, sitosterol, campesterol and brassicasterol are strongly decreased in bile from mutant mice (PubMed:14657202). In contrast, biliary phospholipid and bile acid levels appear unchanged relative to wild-type (PubMed:12444248). The blood plasma of mice with liver-specific or intestine-specific disruption of Abcg5 and Abcg8 has nearly normal levels of cholesterol, and mildly increased levels of sitosterol and campesterol (PubMed:25378657). Mice with intestine-specific disruption of Abcg5 and Abcg8 have strongly increased levels of sitosterol and campesterol in enterocytes, similar to that observed for mice with complete gene disruption (PubMed:25378657). In addition, they display strongly increased levels of sitosterol and campesterol in bile (PubMed:25378657). Mice with liver-specific disruption of Abcg5 and Abcg8 have slightly increased levels of campesterol and sitosterol in the liver, and normal, low levels of sitosterol and campesterol in bile (PubMed:25378657). Enterocytes and liver from mice with liver-specific or intestine-specific disruption of Abcg5 and Abcg8 have normal cholesterol levels (PubMed:25378657).|||N-glycosylated (PubMed:12208867, PubMed:12444248, PubMed:16867993, PubMed:15054092, PubMed:18402465). N-glycosylation is important for efficient export out of the endoplasmic reticulum (PubMed:15054092).|||Seems to have a defective ATP-binding region.|||Up-regulated in liver and small intestine by cholesterol feeding (PubMed:11099417). Possibly mediated by the liver X receptor/retinoic X receptor (LXR/RXR) pathway. Endotoxin (LPS) significantly decreased mRNA levels in the liver but not in the small intestine (PubMed:12777468). http://togogenome.org/gene/10090:Polr2h ^@ http://purl.uniprot.org/uniprot/Q923G2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPB8 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively. Directly interacts with POLR2A (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively (By similarity).|||nucleolus http://togogenome.org/gene/10090:Cma1 ^@ http://purl.uniprot.org/uniprot/P21844 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytoplasmic granule|||Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.|||Mast cells.|||Secreted http://togogenome.org/gene/10090:Ppard ^@ http://purl.uniprot.org/uniprot/P35396|||http://purl.uniprot.org/uniprot/Q546I3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Lys-48'-linked polyubiquitinated; leading to proteasomal degradation. Deubiquitinated and stabilized by OTUD3.|||Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Heart, adrenal and intestine.|||Heterodimer with the retinoid X receptor (By similarity). Interacts (via domain NR LBD) with CRY1 and CRY2 in a ligand-dependent manner (PubMed:28683290, PubMed:28751364).|||Ligand-activated transcription factor key mediator of energy metabolism in adipose tissues (PubMed:35675826). Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand (By similarity).|||Nucleus http://togogenome.org/gene/10090:Alg5 ^@ http://purl.uniprot.org/uniprot/Q9DB25 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family.|||Endoplasmic reticulum membrane|||Required for the assembly of lipid-linked oligosaccharides in kidney epithelial cells, and protein N-glycosylation. Required for polycystin-1 (PKD1) glycosylation and maturation. http://togogenome.org/gene/10090:Ints6 ^@ http://purl.uniprot.org/uniprot/Q6PCM2 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 6 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Chimera.|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Nucleus http://togogenome.org/gene/10090:Pbk ^@ http://purl.uniprot.org/uniprot/Q9JJ78 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Activated by phosphorylation.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Interacts with DLG1 and TP53.|||Phosphorylated; in a cell-cycle dependent manner at mitosis.|||Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization (By similarity). http://togogenome.org/gene/10090:Ddi2 ^@ http://purl.uniprot.org/uniprot/A2ADY9 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although this protein contains the conserved Asp-252 that functions as an active site, this protein does not have proteolytic activity, and may therefore be catalytically inactive.|||Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane. Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1. Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2. Required, with DDI1, for cellular survival following replication stress. Together or redudantly with DDI1, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity.|||Belongs to the DDI1 family.|||Chromosome|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Slc41a1 ^@ http://purl.uniprot.org/uniprot/Q8BJA2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the SLC41A transporter family.|||Cell membrane|||Expressed in heart, brain, kidney, liver and colon.|||Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the plasma membrane. Transporter activity is driven by the inwardly directed electrochemical gradient for Na(+) ions, thus directly depends on the extracellular Na(+) ion concentration set by Na(+)/K(+) pump. Generates circadian cellular Mg(2+) fluxes that feed back to regulate clock-controlled gene expression and metabolism and facilitate higher energetic demands during the day (By similarity). Has a role in regulating the activity of ATP-dependent enzymes, including those operating in Krebs cycle and the electron transport chain (PubMed:33153064).|||Phosphorylated.|||Up-regulated in heart, brain, kidney and down-regulated in liver by low Mg(2+) diet. http://togogenome.org/gene/10090:Spata33 ^@ http://purl.uniprot.org/uniprot/Q8C624 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts (via PQIIIT motif) with PPP3R2 and PPP3CC (PubMed:34446558). Interacts with VDAC2 (PubMed:34446558, PubMed:33087875). Interacts with ATG16L1 (via WD repeats) (PubMed:33087875). Interacts with PPP3R1, PPP3CA and PPP3CB (By similarity).|||Mainly expressed in the postpartum and adult testis. Predominantly expressed in the spermatocytes, as well as spermatogonia and round spermatids (at protein level). Expression increases during the first wave of the spermatogenesis.|||Mice exhibit reduced sperm motility because of an inflexible midpiece, leading to impaired male fertility (PubMed:34446558). Spata33 knockout in Sertoli cells and spermatogenic cells suppresses mitophagy (PubMed:33087875).|||Mitochondrion|||Nucleus|||Plays an important role in sperm motility and male fertility (PubMed:34446558). Required for sperm midpiece flexibility and for the localization of sperm calcineurin to the mitochondria (PubMed:34446558). Promotes mitophagy as well as acts as an autophagy mediator in male germline cells (PubMed:33087875). Links damaged mitochondria to autophagosomes via its binding to the outer mitochondrial membrane protein VDAC2, as well as to key autophagy machinery component ATG16L1 (PubMed:33087875).|||Predominantly expressed in the testis (at protein level) (PubMed:23844118, PubMed:34446558, PubMed:33087875). Expressed in the sperm midpiece (at protein level) (PubMed:34446558, PubMed:33087875).|||cytosol http://togogenome.org/gene/10090:Phactr1 ^@ http://purl.uniprot.org/uniprot/B1B1B8|||http://purl.uniprot.org/uniprot/Q2M3X8|||http://purl.uniprot.org/uniprot/Q3TLK1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphatase and actin regulator family.|||Binds PPP1CA and actin.|||Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regulation of PPP1CA activity. Involved in the regulation of cortical neuron migration and dendrite arborization (PubMed:30256902).|||Binds three actin monomers via the three C-terminal RPEL repeats.|||Cytoplasm|||Interacts (via RPEL repeats) with ACTA1 and PPP1CA; ACTA1 and PPP1CA compete for the same binding site.|||Nucleus|||PHACTR1 knockdown results in migration defects of cortical neurons. Neurons do not migrate to layers II-IV of the cortical plate but remain in the lower part and the intermediate zone.|||Synapse http://togogenome.org/gene/10090:Slc10a3 ^@ http://purl.uniprot.org/uniprot/A0A158SIT6|||http://purl.uniprot.org/uniprot/P21129 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Membrane|||The ubiquitous expression and the conservation of the sequence in distant animal species suggest that the gene codes for a protein with housekeeping functions. http://togogenome.org/gene/10090:Rnd2 ^@ http://purl.uniprot.org/uniprot/Q9QYM5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Expressed specifically in neurons in the brain and spinal cord and also in hepatic stellate cells.|||Interacts with the Rho-GAP domain of RACGAP1. Interacts with UBXD5. Interacts with PRAG1 (By similarity).|||May be specifically involved in neuronal and hepatic functions. Is a C3 toxin-insensitive member of the Rho subfamily (By similarity).|||acrosome membrane http://togogenome.org/gene/10090:Atp6v1e2 ^@ http://purl.uniprot.org/uniprot/Q9D593 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase E subunit family.|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.|||Testis specific.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR. http://togogenome.org/gene/10090:Atp5j ^@ http://purl.uniprot.org/uniprot/P97450 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ATPase subunit F6 family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements. Also involved in the restoration of oligomycin-sensitive ATPase activity to depleted F1-F0 complexes.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Sec31b ^@ http://purl.uniprot.org/uniprot/Q3TZ89 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the coat protein complex II (COPII), may function in vesicle budding and cargo export from the endoplasmic reticulum.|||Belongs to the WD repeat SEC31 family.|||COPII is composed of at least 5 proteins: the SEC23/24 complex, the SEC13/31 complex and SAR1. SEC13 and SEC31 make a 2:2 tetramer that forms the edge element of the COPII outer coat. The tetramer self-assembles in multiple copies to form the complete polyhedral cage. Interacts (via WD 8) with SEC13 (By similarity). Interacts with SEC31A (By similarity).|||COPII-coated vesicle membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Monoubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex, leading to regulate the size of COPII coats. http://togogenome.org/gene/10090:Tbc1d30 ^@ http://purl.uniprot.org/uniprot/Q69ZT9 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||GTPase-activating protein (GAP) with broad specificity. Acts as a GAP for RAB3A. Also exhibits significant GAP activity toward RAB22A, RAB27A, and RAB35 in vitro (By similarity). http://togogenome.org/gene/10090:Pdxp ^@ http://purl.uniprot.org/uniprot/P60487 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HAD-like hydrolase superfamily.|||Cell membrane|||Divalent metal ions. Mg(2+) is the most effective.|||Functions as a pyridoxal phosphate (PLP) phosphatase, which also catalyzes the dephosphorylation of pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), with order of substrate preference PLP > PNP > PMP and therefore plays a role in vitamin B6 metabolism (PubMed:24338473, PubMed:24338687, PubMed:25783190). Also functions as a protein serine phosphatase that specifically dephosphorylates 'Ser-3' in proteins of the actin-depolymerizing factor (ADF)/cofilin family like CFL1 and DSTN. Thereby, regulates cofilin-dependent actin cytoskeleton reorganization, being required for normal progress through mitosis and normal cytokinesis. Does not dephosphorylate phosphothreonines in LIMK1. Does not dephosphorylate peptides containing phosphotyrosine (By similarity).|||Homodimer.|||Inhibited by beryllium trifluoride.|||Ubiquitous. highly expressed in brain (at protein level).|||cytoskeleton|||cytosol|||lamellipodium membrane|||ruffle membrane http://togogenome.org/gene/10090:Cpn2 ^@ http://purl.uniprot.org/uniprot/Q9DBB9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Secreted|||Tetramer of two catalytic chains and two glycosylated inactive chains.|||The 83 kDa subunit binds and stabilizes the catalytic subunit at 37 degrees Celsius and keeps it in circulation. Under some circumstances it may be an allosteric modifier of the catalytic subunit (By similarity). http://togogenome.org/gene/10090:Prkaa1 ^@ http://purl.uniprot.org/uniprot/Q3TUQ7|||http://purl.uniprot.org/uniprot/Q5EG47|||http://purl.uniprot.org/uniprot/Q8BUX6 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.|||Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol.|||Belongs to the POC5 family.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (By similarity). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (By similarity). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (By similarity). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:15878856). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (PubMed:16804075, PubMed:16804077). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:16148943, PubMed:16308421, PubMed:20647423, PubMed:21459323). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (PubMed:16148943, PubMed:16308421). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (PubMed:20647423). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:18439900, PubMed:21258367, PubMed:21205641, PubMed:32912901). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (By similarity). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (By similarity). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21258367, PubMed:21205641). In that process also activates WDR45/WIPI4 (By similarity). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (By similarity). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (PubMed:23283301). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (PubMed:19833968). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (PubMed:20361929). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (By similarity). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance.|||Cytoplasm|||Essential for the assembly of the distal half of centrioles, required for centriole elongation.|||Nucleus|||Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B (By similarity).|||The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.|||Ubiquitinated.|||centriole http://togogenome.org/gene/10090:Pigm ^@ http://purl.uniprot.org/uniprot/Q8C2R7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGM family.|||Endoplasmic reticulum membrane|||Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly (By similarity). http://togogenome.org/gene/10090:Trap1 ^@ http://purl.uniprot.org/uniprot/Q9CQN1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 90 family.|||Binds to the intracellular domain of tumor necrosis factor type 1 receptor. Binds to RB1. Interacts with SRC. Interacts with SDHA.|||Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion matrix http://togogenome.org/gene/10090:Mfsd2a ^@ http://purl.uniprot.org/uniprot/Q9DA75 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily.|||By fasting in liver and brown adipose tissue as well as by cold exposure in brown adipose tissue. Expression following fasting is dependent on glucagon signaling and Ppara.|||Cell membrane|||Endoplasmic reticulum membrane|||Mice are born at Mendelian ratios, but show increased postnatal mortality early in life (PubMed:24828044). Mice are smaller, leaner and have decreased serum, liver and brown adipose triglycerides (PubMed:23209793). After weaning, mice display motor dysfunction with front-paw clasping during tail suspension. Brain size and weight are also significantly lower. Behavioral tests indicate that mice have deficits in learning, and short- and long-term memory, as well as severe anxiety, a phenotype related to omega-3 fatty-acid deficiency. Lipidomic analysis of knockout mice shows strongly reduced levels of docosahexaenoic acid (DHA) in brain accompanied by neuronal cell loss in hippocampus and cerebellum (PubMed:24828044). Mice also show a leaky blood-brain barrier from embryonic stages through to adulthood, while the normal patterning of vascular networks is maintained. Electron microscopy analysis shows an increase in central nervous system-endothelial-cell vesicular transcytosis not associated with tight-junction defects (PubMed:24828040). Mice have an increase in plasma levels of LPC (PubMed:26005868).|||N-glycosylated.|||Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (PubMed:18694395, PubMed:23209793, PubMed:24828044, PubMed:24828040, PubMed:34349262). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain (PubMed:24828044, PubMed:24828040, PubMed:34349262). Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain (PubMed:24828044, PubMed:24828040, PubMed:34349262). Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons (PubMed:24828044, PubMed:34349262). Does not transport docosahexaenoic acid in unesterified fatty acid (PubMed:24828044). Not required for central nervous system vascular morphogenesis (PubMed:24828040).|||Widely expressed. Exhibits an oscillatory pattern of expression in brown adipose tissue and liver consistent with a circadian rhythm. Enriched in brain micro-vessels, where it is specifically present in endothelium constituting the blood-brain barrier (at protein level) (PubMed:24828044, PubMed:24828040). http://togogenome.org/gene/10090:Gprin2 ^@ http://purl.uniprot.org/uniprot/A0A2I3BRN2 ^@ Function ^@ May be involved in neurite outgrowth. http://togogenome.org/gene/10090:Naprt ^@ http://purl.uniprot.org/uniprot/Q8CC86 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the small intestine, liver and kidney.|||Activity is highest with Mn(2+).|||Belongs to the NAPRTase family.|||Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate. Helps prevent cellular oxidative stress via its role in NAD biosynthesis.|||Homodimer.|||Transiently phosphorylated on a His residue during the reaction cycle. Phosphorylation strongly increases the affinity for substrates and increases the rate of nicotinate D-ribonucleotide production. Dephosphorylation regenerates the low-affinity form of the enzyme, leading to product release.|||cytosol http://togogenome.org/gene/10090:Dzip1l ^@ http://purl.uniprot.org/uniprot/B2RR42|||http://purl.uniprot.org/uniprot/Q499E4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DZIP C2H2-type zinc-finger protein family.|||Interacts with SEPTIN2.|||Involved in primary cilium formation (PubMed:28530676). Probably acts as a transition zone protein required for localization of PKD1/PC1 and PKD2/PC2 to the ciliary membrane (By similarity).|||centriole|||cilium basal body http://togogenome.org/gene/10090:Tas2r124 ^@ http://purl.uniprot.org/uniprot/Q7M718 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Or8b47 ^@ http://purl.uniprot.org/uniprot/A0A140T8K0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tas2r123 ^@ http://purl.uniprot.org/uniprot/P59528 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in the duodenum, antrum and fundus (part of the stomach).|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5 (By similarity).|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell.|||This protein was previously referred to as T2R2 but is now considered to be an ortholog of rat TAS2R23. http://togogenome.org/gene/10090:Taf5l ^@ http://purl.uniprot.org/uniprot/Q91WQ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat TAF5 family.|||Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex (By similarity). With TAF6L, acts as an epigenetic regulator essential for somatic reprogramming. Regulates target genes through H3K9ac deposition and MYC recruitment which trigger MYC regulatory network to orchestrate gene expression programs to control embryonic stem cell state (PubMed:31005419).|||Nucleus|||The PCAF complex is composed of a number of TBP-associated factors (TAFS), such as TAF5, TAF5L, TAF6, TAF6L, TAF9, TAF10 and TAF12, PCAF, and also PCAF-associated factors (PAFs), such as TADA2L/ADA2, TADA3L/ADA3 and SPT3. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9 (By similarity). http://togogenome.org/gene/10090:Nmt2 ^@ http://purl.uniprot.org/uniprot/A2AJH3|||http://purl.uniprot.org/uniprot/F7APP3|||http://purl.uniprot.org/uniprot/O70311|||http://purl.uniprot.org/uniprot/Q3THR4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. Also able to mediate N-terminal lysine myristoylation of proteins: catalyzes myristoylation of ARF6 on both 'Gly-2' and 'Lys-3'. Lysine myristoylation is required to maintain ARF6 on membranes during the GTPase cycle.|||Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.|||Belongs to the NMT family.|||Cytoplasm|||Membrane http://togogenome.org/gene/10090:Bach1 ^@ http://purl.uniprot.org/uniprot/P97302 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. CNC subfamily.|||Heterodimer of BACH1 and MAFK.|||Nucleus|||Transcriptional regulator that acts as repressor or activator, depending on the context (PubMed:8887638, PubMed:19170764). Binds to NF-E2 DNA binding sites (PubMed:8887638, PubMed:19170764). Plays important roles in coordinating transcription activation and repression by MAFK (PubMed:8887638). Together with MAF, represses the transcription of genes under the control of the NFE2L2 oxidative stress pathway (By similarity).|||Ubiquitinated by the SCF(FBXL17) complex, leading to its degradation by the proteasome.|||Ubiquitous. http://togogenome.org/gene/10090:Cyp2w1 ^@ http://purl.uniprot.org/uniprot/E9Q816 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that may play a role in retinoid and phospholipid metabolism. Catalyzes the hydroxylation of saturated carbon hydrogen bonds. Hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may regulate atRA clearance. Other retinoids such as all-trans retinol and all-trans retinal are potential endogenous substrates. Catalyzes both epoxidation of double bonds and hydroxylation of carbon hydrogen bonds of the fatty acyl chain of 1-acylphospholipids/2-lysophospholipids. Can metabolize various lysophospholipids classes including lysophosphatidylcholines (LPCs), lysophosphatidylinositols (LPIs), lysophosphatidylserines (LPSs), lysophosphatidylglycerols (LPGs), lysophosphatidylethanolamines (LPEs) and lysophosphatidic acids (LPAs). Has low or no activity toward 2-acylphospholipids/1-lysophospholipids, diacylphospholipids and free fatty acids. May play a role in tumorigenesis by activating procarcinogens such as aflatoxin B1, polycyclic aromatic hydrocarbon dihydrodiols and aromatic amines. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Cell membrane|||Detected in colon, ileum, and testes.|||Endoplasmic reticulum lumen|||Microsome membrane http://togogenome.org/gene/10090:Tmem87a ^@ http://purl.uniprot.org/uniprot/A2AQJ5|||http://purl.uniprot.org/uniprot/A2AQJ6|||http://purl.uniprot.org/uniprot/Q8BXN9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LU7TM family. TMEM87 subfamily.|||Cell membrane|||Golgi apparatus membrane|||May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN) (By similarity). In one study, shown to be a component of a novel mechanoelectrical transduction pathway which is involved in cell adhesion and migration, and is thought to act either as a mechanically activated ion channel or as an accessory protein which modulates an unidentified mechanically activated ion channel (PubMed:32228863). In another study, neither basal nor mechanically activated channel activity has been observed and, based on structural similarity with WLS, has been suggested to function as a trafficking chaperone for membrane-associated cargo (By similarity).|||Membrane|||ruffle http://togogenome.org/gene/10090:Atp2a2 ^@ http://purl.uniprot.org/uniprot/O55143|||http://purl.uniprot.org/uniprot/Q5DTI2 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.|||Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation.|||Endoplasmic reticulum membrane|||Has different conformational states with differential Ca2+ affinity. The E1 conformational state (active form) shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) affinity. Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (PubMed:22971924). Inhibited by sarcolipin (SLN) and myoregulin (MRLN). The inhibition is blocked by VMP1 (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Stabilizes SERCA2 in its E2 state (By similarity).|||Highly up-regulated during osteoclast differentiation.|||Interacts with TRAM2 (via C-terminus).|||Interacts with sarcolipin (SLN); the interaction inhibits ATP2A2 Ca(2+) affinity (By similarity). Interacts with phospholamban (PLN); the interaction inhibits ATP2A2 Ca(2+) affinity (PubMed:22971924). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Interacts with HAX1. Interacts with S100A8 and S100A9 (PubMed:18403730). Interacts with SLC35G1 and STIM1. Interacts with TMEM203 (By similarity). Interacts with TMEM64 and PDIA3 (PubMed:23395171). Interacts with TMX2. Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2. Interacts with ULK1 (By similarity). Interacts with S100A1 in a Ca(2+)-dependent manner (By similarity). Interacts with TUNAR (PubMed:35036403). Interacts with FLVCR2; this interaction occurs in the absence of heme and promotes ATP2A2 proteasomal degradation; this complex is dissociated upon heme binding (PubMed:32973183). Interacts with FNIP1 (PubMed:35412553).|||Involved in the regulation of the contraction/relaxation cycle (PubMed:23395171). Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation (PubMed:23395171). Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation (PubMed:23395171).|||Isoform 2 is highly expressed in heart and slow twitch skeletal muscle. Isoform 2 is widely expressed.|||Membrane|||Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity.|||PLN and SLN both have a single transmembrane helix; both occupy a similar binding site that is situated between the ATP2A2 transmembrane helices.|||Sarcoplasmic reticulum collapse and volume reduction. Although dimensions of cardiomyocyte are not affected, total surface area is significantly increased, resulting in increased T-tubule density.|||Sarcoplasmic reticulum membrane|||Serotonylated on Gln residues by TGM2 in response to hypoxia, leading to its inactivation.|||This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation. Also modulates ER contacts with lipid droplets, mitochondria and endosomes (By similarity). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis. http://togogenome.org/gene/10090:Iffo2 ^@ http://purl.uniprot.org/uniprot/Q8R2V2 ^@ Sequence Caution|||Similarity ^@ Belongs to the intermediate filament family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part. http://togogenome.org/gene/10090:Homer2 ^@ http://purl.uniprot.org/uniprot/E9Q4F9|||http://purl.uniprot.org/uniprot/Q9QWW1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Homer family.|||Cell membrane|||Cytoplasm|||Expressed in olfactory bulb, hippocampus, thalamus and heart (PubMed:9808459). Expressed in the cochlea, organ of Corti. Expression is particularly enriched in the tips of stereocilia of both inner and outer hair cells (PubMed:25816005).|||Forms coiled-coil structures coiled-coil structures that mediate homo- and heteromultimerization. Interacts with NFATC2; interaction is reduced by AKT activation. Interacts with NFATC1 and NFATC4 (By similarity). Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA (By similarity).|||Homozygous knockout mice exhibit early onset progressive hearing loss.|||Postsynaptic density|||Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2 (By similarity). Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses (By similarity) Required for normal hearing (PubMed:25816005). Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (By similarity).|||Synapse|||stereocilium http://togogenome.org/gene/10090:Flywch1 ^@ http://purl.uniprot.org/uniprot/Q8CI03 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CTNNB1 (when unphosphorylated), perhaps preventing interaction of CTNNB1 with TCF4, and thereby regulating transcription activation; phosphorylation of CTNNB1 may inhibit the interaction.|||Nucleus|||Transcription cofactor. Negatively regulates transcription activation by catenin beta-1 CTNNB1, perhaps acting by competing with TCF4 for CTNNB1 binding. May play a role in DNA-damage response signaling. Binds specifically to DNA sequences at peri-centromeric chromatin loci.|||centromere http://togogenome.org/gene/10090:Lgi1 ^@ http://purl.uniprot.org/uniprot/Q9JIA1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum|||Expressed in the brain (at protein level) (PubMed:16787412). Expressed in cerebellar cortex basket cell terminals (at protein level) (PubMed:26269648). Highly expressed in the dentate gyrus and CA3 field of the hippocampus.|||Glycosylated.|||Golgi apparatus|||Oligomer (By similarity). Interacts with KCNA1 within a complex containing KCNA1, KCNA4 and KCNAB1 (By similarity). Part of a complex containing ADAM22, DLG4/PSD95 and CACNG2 (stargazin) (By similarity). Can bind to ADAM11 and ADAM23.|||Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors. Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway (By similarity).|||Secreted|||Synapse http://togogenome.org/gene/10090:Tlk1 ^@ http://purl.uniprot.org/uniprot/Q8C0V0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cell-cycle regulated, maximal activity in S-phase. Inactivated by phosphorylation at Ser-743, potentially by CHEK1 (By similarity).|||Heterodimer with TLK2.|||Nucleus|||Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly (By similarity). Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10' (By similarity).|||Ubiquitously expressed in all tissues examined. http://togogenome.org/gene/10090:Vstm2a ^@ http://purl.uniprot.org/uniprot/Q8R0A6 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain. Expressed in neurons. Expressed in adipose precursor cells in epididymal white adipose tissue (at protein level). Strongly expressed in adipose precursor cells. Weakly expressed in adipocytes.|||Expressed in embryo in subcutaneous white adipose tissue from 16.5 days post coitum (dpc) to 4 days postnatal (P4). Expressed early in pups in visceral epididymal white adipose tissue at 4 days postnatal (P4) and strongly decreases from P7 to P56 (at protein level).|||Homodimer.|||N-glycosylated. N-linked glycosylation on Asn-35 and Asn-175 is critical for secretion but not for preadipocyte cell differentiation activity.|||Plays a role in the regulation of the early stage of white and brown preadipocyte cell differentiation. Promotes adipogenic commitment of preadipocytes by increasing gene expression of the transcription factor PPARG in a BMP4-dependent signaling pathway.|||Secreted|||Up-regulated is response to high-fat feeding (at protein level) (PubMed:28052263). Up-regulated by the transcription factor PPARG in a BMP4-signaling dependent manner. Up-regulated during adipocyte differentiation. http://togogenome.org/gene/10090:Ttc39c ^@ http://purl.uniprot.org/uniprot/A0A3Q4EGC9|||http://purl.uniprot.org/uniprot/Q8VE09 ^@ Similarity ^@ Belongs to the TTC39 family. http://togogenome.org/gene/10090:Cand2 ^@ http://purl.uniprot.org/uniprot/Q6ZQ73 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAND family.|||Binds TBP, CNOT3 and UBE3C.|||Highly expressed in embryonic limb buds.|||Nucleus|||Probable assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes.|||Ubiquitinated and targeted for proteasomal degradation. http://togogenome.org/gene/10090:Smim35 ^@ http://purl.uniprot.org/uniprot/E9Q2Z6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cnn1 ^@ http://purl.uniprot.org/uniprot/B2RSH3|||http://purl.uniprot.org/uniprot/Q08091|||http://purl.uniprot.org/uniprot/Q8CBQ2 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the calponin family.|||Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1.|||Smooth muscle, and tissues containing significant amounts of smooth muscle.|||Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity. http://togogenome.org/gene/10090:Hsf2bp ^@ http://purl.uniprot.org/uniprot/Q9D4G2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Cytoplasm|||Detected at low levels from birth to 3 days post partum, thereafter the expression level increases from 5 days post partum to adult. In spermatocytes, shows punctate localization along chromosome axes specifically in early meiotic prophase I cells. Foci start to appear from the leptotene stage, reach their greatest number in the zygotene stage, persist until the early pachytene stage, and finally disappear in the late pachytene stage (PubMed:30760716).|||Expressed in testis and, to a lesser extent, in lung and muscle.|||Interacts (via C-terminus) with BNC1 (PubMed:23707421). Associates with HSF2. The interaction seems to occur between the trimerization domain of HSF2 and the N-terminal hydrophilic region of HSF2BP (By similarity). Interacts (via N-terminus) with BRME1 (PubMed:32463460, PubMed:32460033, PubMed:32345962). Interacts with BRCA2 and BRME1; the interactions are direct and allow the formation of a ternary complex (PubMed:32345962, PubMed:32460033, PubMed:32463460, PubMed:31242413, PubMed:30760716, PubMed:32845237). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (PubMed:32345962, PubMed:30760716).|||Male mutants are infertile (PubMed:31242413, PubMed:30760716). They have smaller-than-normal testes with no sperm (PubMed:31242413, PubMed:30760716). Female mutants exhibit a fertility with 40% reduction in litter size compared to wild-type females. They show reduced follicle formation (PubMed:30760716, PubMed:32845237). Mutant oocytes show a delay in prophase I progression with the majority of cells at zygotene stage in 17.5 days post-coitum (dpc) females (PubMed:32845237).|||Meiotic recombination factor component of recombination bridges involved in meiotic double-strand break repair. Modulates the localization of recombinases DMC1:RAD51 to meiotic double-strand break (DSB) sites through the interaction with BRCA2 and its recruitment during meiotic recombination. Indispensable for the DSB repair, homologous synapsis, and crossover formation that are needed for progression past metaphase I, is essential for spermatogenesis and male fertility (PubMed:31242413, PubMed:32345962, PubMed:32463460, PubMed:30760716). Required for proper recombinase recruitment in female meiosis (PubMed:30760716, PubMed:32845237). Inhibits BNC1 transcriptional activity during spermatogenesis, probably by sequestering it in the cytoplasm (PubMed:23707421). May be involved in modulating HSF2 activation in testis (By similarity).|||Sumoylated by UBE2I in response to MEKK1-mediated stimuli. http://togogenome.org/gene/10090:Slc44a2 ^@ http://purl.uniprot.org/uniprot/Q8BY89 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CTL (choline transporter-like) family.|||Cell membrane|||Choline/H+ antiporter, mainly in mitochodria. Also acts as a low-affinity ethanolamine/H+ antiporter, regulating the supply of extracellular ethanolamine (Etn) for the CDP-Etn pathway, redistribute intracellular Etn and balance the CDP-Cho and CDP-Etn arms of the Kennedy pathway.|||Expressed at high levels in lung, colon, inner ear and spleen (at protein level). Progressively lower levels in brain, tongue, liver and kidney (at protein level). In the kidney, prominent expression in glomeruli in the lining of Bowman's capsule and on the mesangial cells adjacent to the vessels within the glomerulus (at protein level). Strongly expressed on the membranes of splenocytes and in lung parenchyme (at protein level).|||Expressed at higher levels than isoform 2 in colon, heart, kidney, lung, cochlea, tongue and muscle, as well as in the inner ear.|||Glycosylated, glycosylation differs from tissue to tissue. The molecular mass of the mature glycosylated protein is highest in kidney, followed by lung, colon and spleen, then brain and tongue.|||Interacts with COCH.|||Mitochondrion outer membrane|||Predominantly expressed in brain, liver and spleen.|||Produced by alternative promoter usage. http://togogenome.org/gene/10090:Fem1al ^@ http://purl.uniprot.org/uniprot/Q8C0T1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fem-1 family.|||Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1A.|||Cytoplasm|||Mitochondrion|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(FEM1A) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2, leading to their ubiquitination and degradation. http://togogenome.org/gene/10090:Or9a4 ^@ http://purl.uniprot.org/uniprot/Q8VF31 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adssl1 ^@ http://purl.uniprot.org/uniprot/P28650|||http://purl.uniprot.org/uniprot/Q3UBP0 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adenylosuccinate synthetase family.|||Binds 1 Mg(2+) ion per subunit.|||Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.|||Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.|||Cytoplasm|||High levels in muscle.|||Homodimer.|||Membrane|||Plays an important role in the de novo pathway of purine nucleotide biosynthesis.|||Weakly inhibited by AMP non-competitively to all substrates. Inhibited by IMP non-competitively with respect to GTP. Inhibited by fructose 1,6-bisphosphate competitively with respect to IMP. http://togogenome.org/gene/10090:Apom ^@ http://purl.uniprot.org/uniprot/Q9Z1R3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family. Highly divergent.|||Expressed by the liver; secreted in plasma.|||Interacts with LRP2; LRP2 mediates APOM renal uptake and subsequent lysosomal degradation.|||Probably involved in lipid transport. Can bind sphingosine-1-phosphate, myristic acid, palmitic acid and stearic acid, retinol, all-trans-retinoic acid and 9-cis-retinoic acid (By similarity).|||Secreted http://togogenome.org/gene/10090:Irf2bp2 ^@ http://purl.uniprot.org/uniprot/E9Q1P8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional corepressor in a IRF2-dependent manner, this repression is not mediated by histone deacetylase activities. Represses the NFAT1-dependent transactivation of NFAT-responsive promoters. Acts as a coactivator of VEGFA expression in cardiac and skeletal muscles. Plays a role in immature B-cell differentiation (By similarity).|||Belongs to the IRF2BP family.|||Cytoplasm|||Interacts with IRF2. Part of a corepressor complex containing IRF2 and IRF2BP1. Interacts with VGLL4 (By similarity).|||Nucleus|||Phosphorylation at Ser-343 is required for nuclear targeting.|||The C-terminal RING-type zinc finger domain is sufficient for interaction with IRF2. http://togogenome.org/gene/10090:Ptma ^@ http://purl.uniprot.org/uniprot/P26350|||http://purl.uniprot.org/uniprot/Q0VGU2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pro/parathymosin family.|||Covalently linked to a small RNA of about 20 nucleotides.|||Interacts with NUPR1; regulates apoptotic process.|||Nucleus|||Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections. http://togogenome.org/gene/10090:Palb2 ^@ http://purl.uniprot.org/uniprot/Q3U0P1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Homooligomer; dissociated upon DNA damage thus allowing association with BRCA1. Oligomerization is essential for its focal accumulation at DNA breaks. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts with BRCA1 and this interaction is essential for its function in HRR. Interacts with RAD51AP1 and MORF4L1/MRG15. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (By similarity). Within the complex, interacts with ERCC5/XPG and BRCA2 (By similarity). Interacts with BRCA2, RAD51C, RAD51 and XRCC3; the interactions are direct and it may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with POLH; the interaction is direct (By similarity).|||Interaction with BRCA2 occurs through a hydrophobic pocket at the crossover between WD repeats 4 and 5.|||Nucleus|||Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks. Strongly stimulates the DNA strand-invasion activity of RAD51, stabilizes the nucleoprotein filament against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome the suppressive effect of replication protein A (RPA). Functionally cooperates with RAD51AP1 in promoting of D-loop formation by RAD51. Serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is essential for homologous recombination. Via its WD repeats is proposed to scaffold a HR complex containing RAD51C and BRCA2 which is thought to play a role in HR-mediated DNA repair. Essential partner of BRCA2 that promotes the localization and stability of BRCA2. Also enables its recombinational repair and checkpoint functions of BRCA2. May act by promoting stable association of BRCA2 with nuclear structures, allowing BRCA2 to escape the effects of proteasome-mediated degradation. Binds DNA with high affinity for D loop, which comprises single-stranded, double-stranded and branched DNA structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with BRCA2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity (By similarity).|||The chromatin-association motif (ChAM) mediates association with chromatin, probably through nucleosome core particles, independently from binding to D loop, ssDNA or dsDNA structures.|||The coiled coil domain mediates self-association. http://togogenome.org/gene/10090:Agtpbp1 ^@ http://purl.uniprot.org/uniprot/Q641K1 ^@ Cofactor|||Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apparent retained intron. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||By axonal regeneration.|||Cytoplasm|||Defects in Agtpbp1 are the cause of Purkinje cell degeneration (pcd). Pcd is a spontaneous mutation that results in adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons and selected thalamic neurons, and causes defective spermatogenesis. Pcd mice also manifest cerebellar atrophy and a peripheral nerve degeneration resulting in pure motor or motor-predominant neuropathy. Motoric femoral quadriceps nerves are characterized by reduced total calibers, a loss of myelinated axons, perturbed axon morphology, and macrophage activation. The amount of motor neurons in the ventral horns of lumbar spinal cords is reduced. These anomalies are accompanied by dysregulated tubulin polyglutamylation (PubMed:30420557). Defects in mitochondrial metabolic functions are also observed. The molecular causes of neurodegeneration are probably due to an accumulation of glutamylation, either tubulin hyperglutamylation or another hyperglutamylated target proteins. An increase of intranuclear localization of lysyl oxidase (Lox) propeptide, which interferes with NF-kappa-B Rela signaling and microtubule-associated protein regulation of microtubule stability is also observed, possibly leading to underdevelopment of Purkinje cell dendrites.|||Highly expressed in differentiating neurons. From 16.5 dpc, expression is widespread in brain, spinal cord, and peripheral nervous tissue. Within the developing CNS, expression is restricted to regions of brain and spinal cord containing differentiating neurons.|||Interacts with MYLK.|||Knockout pcd mice show hyperglutamylation of alpha- and beta-tubulins in the brain (PubMed:22170066). Knockout mice promote somatic cell reprogramming and higher litter size at birth (PubMed:29593216).|||Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:21074048, PubMed:22170066, PubMed:25103237, PubMed:30420557, PubMed:29593216). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:22170066, PubMed:25103237, PubMed:30420557). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:21074048). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK (PubMed:21074048, PubMed:22170066). Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216).|||Mitochondrion|||Nucleus|||Widely expressed. Highly expressed in the cerebellum and cortex of adult mouse brain. Expressed at similar levels in both the cerebellum and the cortex throughout all developmental stages. Also expressed in sciatic nerve transection, spinal motor neurons undergoing axon regeneration, testis, heart, eye, lung, pancreas, intestine, stomach, pituitary, spleen, adrenal, kidney and in developing brain. Expression in cranial motor nuclei is the same as that observed in uninjured primary motor neurons. Expression is prevalent in sensory neurons and hippocampal CA3 neurons in addition to regenerating motor neurons.|||cytosol http://togogenome.org/gene/10090:Pramel20 ^@ http://purl.uniprot.org/uniprot/Q66JY9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Serpina3a ^@ http://purl.uniprot.org/uniprot/H7BWY0|||http://purl.uniprot.org/uniprot/Q6P4P1 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha-1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Tcf7 ^@ http://purl.uniprot.org/uniprot/Q00417|||http://purl.uniprot.org/uniprot/Q80UF1 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aberrant expression of Vgamma2 T-cell receptor in alpha-beta T-cells (PubMed:17218525). Reduced frequency of DN1d cells, a subset of DN1 precursor thymocytes (PubMed:30413363). Decreased number of natural killer receptor-positive lymphoid tissue inducer T-cells (PubMed:23562159). Increased expression of Il17 in Vgamma1.1 and Vgamma2 gamma-delta T-cells (PubMed:23562159). Loss of Lef1 expression in Vgamma1.1 and Vgamma2 gamma-delta T-cells (PubMed:23562159). Loss of Cd27 expression in Il17a expressing gamma-delta T-cells (PubMed:23562159). Double knockout of Sox13 and Tcf7/Tcf1 show a reduced number of DN1d cells (PubMed:30413363).|||Belongs to the TCF/LEF family.|||Binds the armadillo repeat of CTNNB1 and forms a stable complex (By similarity). Binds TLE5, TLE1, TLE2, TLE3 and TLE4 (By similarity). Interacts with MLLT11 (By similarity). Interacts with DAZAP2 (By similarity).|||Defects in Tcf7 may allow the formation of epithelial tumors.|||Expressed in the yolk sac (at protein level) (PubMed:30413363). Expressed in the mandibular molar tooth mesenchyme at 13.5 dpc (PubMed:27713059).|||Interacts (via N-terminus) with SOX13; inhibits WNT-mediated transcriptional activity.|||Nucleus|||T-cell specific. Expressed in triple negative 2 subpopulations of T-cells and both the gamma-delta and alpha-beta T-cell lineages (PubMed:17218525). Expressed in Il7 receptor positive innate-like T-cells in the mesenteric lymph nodes and spleen (at protein level) (PubMed:23562159).|||Transcriptional activator involved in T-cell lymphocyte differentiation. Necessary for the survival of CD4(+) CD8(+) immature thymocytes. Isoforms lacking the N-terminal CTNNB1 binding domain cannot fulfill this role. Binds to the T-lymphocyte-specific enhancer element (5'-WWCAAAG-3') found in the promoter of the CD3E gene. Represses expression of the T-cell receptor gamma gene in alpha-beta T-cell lineages (PubMed:17218525). Inhibits the developmental program of IL17A effector gamma-delta T-cell subsets via regulating the transcription of T-cell lineage effector proteins (PubMed:23562159, PubMed:30413363). Required for the development of natural killer receptor-positive lymphoid tissue inducer T-cells (PubMed:23562159). TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7 and CTNNB1 (By similarity). May also act as feedback transcriptional repressor of CTNNB1 and TCF7L2 target genes. http://togogenome.org/gene/10090:Dppa4 ^@ http://purl.uniprot.org/uniprot/E9PUG8|||http://purl.uniprot.org/uniprot/Q8CCG4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in 4-cell embryo, morula and blastocyst. At 7.5 dpc, detected in the epiblast. At 10.0 dpc, expressed in the primordial germ cells and at 12.0 dpc in the embryonic gonads. At 14.5 dpc, expression is restricted to testis. 6 days after birth, still detected in primitive type A spermatogonia. Expressed in undifferentiated embryonic stem cells, but expression decreases upon differentiation (at protein level).|||Expressed in pluripotent embryonic cells, but not in differentiated somatic tissues.|||Interacts with DPPA2 (PubMed:21896782). Interacts with PCGF1 (By similarity).|||May be involved in the maintenance of active epigenetic status of target genes. May inhibit differentiation of embryonic stem (ES) cells into a primitive ectoderm lineage.|||Nucleus|||The mortality of mutant animals is increased at birth and most die within 3 days. The few surviving neonates show growth retardation, but they catch up with wild-type mice by 20 weeks of age. http://togogenome.org/gene/10090:Glyatl3 ^@ http://purl.uniprot.org/uniprot/E9Q5L8 ^@ Function ^@ Catalyzes the conjugation of long-chain fatty acyl-CoA thioester and glycine to produce long-chain N-(fatty acyl)glycine, an intermediate in the primary fatty acid amide biosynthetic pathway. http://togogenome.org/gene/10090:Ppp2cb ^@ http://purl.uniprot.org/uniprot/P62715|||http://purl.uniprot.org/uniprot/Q8BN07 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP phosphatase family.|||Belongs to the PPP phosphatase family. PP-1 subfamily.|||Binds 2 manganese ions per subunit.|||Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events. PP2A can modulate the activity of phosphorylase B kinase, casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.|||Cytoplasm|||May be monoubiquitinated by NOSIP.|||Nucleus|||PP2A consists of a common heterodimeric core enzyme (composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65) (subunit A)) that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Binds PPME1. May indirectly interact with SGO1, most probably through regulatory B56 subunits. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with TBCD. Interacts with CTTNBP2NL. Interacts with PTPA.|||Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation (By similarity).|||Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (Lcmt1) and protein phosphatase methylesterase 1 (Ppme1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization (By similarity).|||centromere|||spindle pole http://togogenome.org/gene/10090:Polr2m ^@ http://purl.uniprot.org/uniprot/Q6P6I6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GRINL1 family.|||Isoform 1 appears to be stable component of the Pol II(G) complex form of RNA polymerase II. Pol II synthesizes mRNA precursors and many functional non-coding RNAs and is the central component of the basal RNA polymerase II transcription machinery. Isoform 1 may play a role in Mediator-dependent regulation of transcription activation. Isoform 1 acts in vitro as negative regulator of transcriptional activation; this repression is relieved by the Mediator complex, which restores Pol II(G) activator-dependent transcription to a level equivalent to that of Pol II (By similarity).|||Isoform 1 is a component of the Pol II(G) complex, which contains the RNA polymerase II (Pol II) core complex subunits and Polr2m isoform 1 and appears to be an abundant form of Pol II.|||Nucleus http://togogenome.org/gene/10090:Esyt1 ^@ http://purl.uniprot.org/uniprot/Q3U7R1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic.|||Belongs to the extended synaptotagmin family.|||Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity). Binds calcium (via the C2 domains) and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. Helps tether the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane (By similarity).|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with ESYT2 and ESYT3 (By similarity). Interacts (phosphorylated form) with SLC2A4.|||Phosphorylated on Ser residues in insulin-treated adipocytes (in vitro); this promotes interaction with SLC2A4.|||The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium. The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for translocation to the cell membrane in response to increased cytosolic calcium levels (By similarity).|||The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior (By similarity). http://togogenome.org/gene/10090:Ccr10 ^@ http://purl.uniprot.org/uniprot/Q9JL21 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed at high levels in small intestine, colon, lymph nodes, Peyer patches and at lower levels in thymus, lung and spleen.|||Receptor for chemokines SCYA27 and SCYA28. Subsequently transduces a signal by increasing the intracellular calcium ions level. http://togogenome.org/gene/10090:Parp3 ^@ http://purl.uniprot.org/uniprot/Q3ULW8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Chromosome|||Interacts with PARP1; leading to activate PARP1 in absence of DNA. Interacts with PRKDC. Interacts with XRCC5/Ku80; the interaction is dependent on nucleic acids. Interacts with XRCC6/Ku70; the interaction is dependent on nucleic acids. Interacts with EZH2, HDAC1, HDAC2, SUZ12, YY1, LRIG3 and LIG4.|||Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:21270334, PubMed:24598253). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (By similarity). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (By similarity). Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6 (By similarity). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (By similarity). Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA (By similarity). Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ (By similarity). Suppresses G-quadruplex (G4) structures in response to DNA damage (By similarity). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (By similarity). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (By similarity). Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin (PubMed:26000965). In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks (By similarity).|||No visible phenotype in normal conditions, but mutant mice are sensitive to ionizing radiation (PubMed:21270334). In B-cells, class switch recombination is increased, while somatic hypermutation is unaffected, due to increased occupancy of Aicda/Aid at the donor switch region (PubMed:26000965).|||Nucleus|||centriole|||centrosome http://togogenome.org/gene/10090:Lrrn1 ^@ http://purl.uniprot.org/uniprot/Q61809 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in brain.|||Membrane http://togogenome.org/gene/10090:Suz12 ^@ http://purl.uniprot.org/uniprot/E9PW15|||http://purl.uniprot.org/uniprot/Q80U70 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family.|||Chromosome|||Component of the PRC2 complex, which consists of the core subunits EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:19026780, PubMed:20144788). Within the complex, interacts (via C2H2 zinc finger domain) with JARID2 and EPOP; JARID2 and EPOP compete for SUZ12 binding (By similarity). Also interacts with AEBP2 and PHF19 (By similarity). Forms a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (By similarity). Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin (By similarity). The minimum components required for methyltransferase activity of the PRC2/EZH2 complex are EED, EZH2 and SUZ12 (By similarity). The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with WDR77 (PubMed:16712789). Interacts with histone H1. Interacts with CDYL (By similarity). Interacts with BMAL1 (PubMed:23970558). Interacts with EZHIP (via C-terminal region) (By similarity). Interacts with ARMC12 (By similarity).|||Expressed in embryonic stem cells.|||Expression increases in prostate during prostate tumor development.|||Mice exhibit early embryonic lethality and defects in gastrulation accompanied by reduced methylation of 'Lys-27' of histone H3.|||Nucleus|||Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8.|||Sumoylated, probably by PIAS2.|||Unknown reasons. http://togogenome.org/gene/10090:Gm5926 ^@ http://purl.uniprot.org/uniprot/E9PWJ8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Glis3 ^@ http://purl.uniprot.org/uniprot/Q0GE24|||http://purl.uniprot.org/uniprot/Q6XP49 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as both a repressor and activator of transcription. Binds to the consensus sequence 5'-GACCACCCAC-3'.|||Belongs to the GLI C2H2-type zinc-finger protein family.|||In the embryo, expressed at high levels in the kidney and testis. In the adult, expressed at high levels in the kidney and uterus and at lower levels in the brain, lung, skeletal muscle and pancreas.|||In the embryo, expression is detected between days 6.5 and 14.5, particularly during neurulation. At embryonic days 11.5 to 12.5, expression is high in the interdigital regions destined to undergo apoptosis.|||Nucleus http://togogenome.org/gene/10090:Izumo2 ^@ http://purl.uniprot.org/uniprot/Q9DA16 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Izumo family.|||Izumo is the name of a Japanese shrine to marriage.|||Membrane http://togogenome.org/gene/10090:Gm20808 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Fzd10 ^@ http://purl.uniprot.org/uniprot/Q149J3|||http://purl.uniprot.org/uniprot/Q8BKG4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Interacts with MYOC (By similarity). Interacts with WNT7B (PubMed:15923619).|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Receptor for Wnt proteins (PubMed:15923619). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:15923619). The canonical Wnt/beta-catenin signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (Probable).|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Alyref ^@ http://purl.uniprot.org/uniprot/O08583 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.|||Arg-50 and Arg-203 are dimethylated, probably to asymmetric dimethylarginine. Arginine methylation reduces RNA binding (By similarity).|||Belongs to the THOC4 family.|||Citrullinated by PADI4.|||Cytoplasm|||Export adapter involved in nuclear export of spliced and unspliced mRNA. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway) (PubMed:9119228, PubMed:10786854, PubMed:11158589). Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm. TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production; ALYREF/THOC4 mediates the recruitment of the TREX complex to the intronless viral mRNA. Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Involved in transcription elongation and genome stability. Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling (By similarity).|||Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Homomultimer (By similarity). Is part of several complexes involved in mRNA processing and export (By similarity). Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have a dynamic structure involving ATP-dependent remodeling; in the complex interacts (via C-terminus) directly with DDX39B and interacts directly with THOC1 and THOC2 (By similarity). Found in mRNA splicing-dependent exon junction complexes (EJC) (By similarity). Identified in the spliceosome C complex (By similarity). Found in a mRNP complex with UPF3A and UPF3B (By similarity). Interacts with RBM8A, NCBP1, THOC5, LEF1, RUNX1, EIF4A3, RNPS1, SRRM1, IWS1 and EXOSC1 (By similarity). Interacts with RBM15B. Interacts with NXF1; the interaction is direct (PubMed:10786854).|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Pcolce ^@ http://purl.uniprot.org/uniprot/Q3UIP2|||http://purl.uniprot.org/uniprot/Q3UN82|||http://purl.uniprot.org/uniprot/Q61398 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the C-terminal propeptide of type I procollagen and enhances procollagen C-proteinase activity.|||Expressed in interstitial connective tissues like tendons, calvaria, skin and at a lower level in heart and skeletal muscle.|||Interacts with EFEMP2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Processed from a 55 kDa form to 36 kDa and 34 kDa forms.|||Secreted http://togogenome.org/gene/10090:Pdk1 ^@ http://purl.uniprot.org/uniprot/Q8BFP9 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PDK/BCKDK protein kinase family.|||Homodimer, and heterodimer with PDK2. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (By similarity).|||Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress (By similarity).|||Mitochondrion matrix|||Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and JAK2 (in vitro), and this may also occur in cancer cells that express constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at Tyr-241 and Tyr-242 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect (By similarity).|||Up-regulated by glucose and palmitate. Up- regulated via the HIF1A signaling pathway in response to hypoxia. http://togogenome.org/gene/10090:Rab38 ^@ http://purl.uniprot.org/uniprot/Q5FW76|||http://purl.uniprot.org/uniprot/Q8QZZ8 ^@ Activity Regulation|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Defects in Rab38 are the cause of a form of oculocutaneous albinism known as the chocolate (cht) phenotype. Mice exhibit a brown coat similar in color to mice with a mutation in tyrosinase-related protein 1 (TYRP1). The targeting of TYRP1 protein to the melanosome is impaired in Rab38(cht)/Rab38(cht) melanocytes.|||Interacts with ANKRD27 (By similarity).|||Melanosome|||Melanosome membrane|||Membrane|||Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and Mycobacterium (By similarity). May be involved in melanosomal transport and docking. Involved in the proper sorting of TYRP1. Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with ANKRD27 and VAMP7 (PubMed:21187289). Plays an important role in the control of melanin production and melanosome biogenesis (By similarity). In concert with RAB32, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (PubMed:26620560).|||Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. The BLOC-3 complex composed of HPS1 and HPS4 acts as its GEF, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form. SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity (PubMed:26620560).|||The small GTPases Rab are key regulators in vesicle trafficking.|||phagosome|||phagosome membrane http://togogenome.org/gene/10090:Zfr ^@ http://purl.uniprot.org/uniprot/O88532 ^@ Developmental Stage|||Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Cytoplasmic granule|||Expressed in Sertoli cells, spermatocytes, primary and growing oocytes and granulosa cells (at protein level). Expressed in testis, ovary and brain.|||Expressed in embryos at 5.5, 6.5 and 7 dpc (at protein level). Expressed in the trophoectoderm cells and inner cell mass of blastocysts (at protein level).|||Found in a cytoplasmic mRNP complex with STAU2. Does not interact with STAU1 (By similarity). Interacts with STAU2.|||Involved in postimplantation and gastrulation stages of development. Binds to DNA and RNA. Involved in the nucleocytoplasmic shuttling of STAU2 (By similarity).|||Knockout mice form mesoderm but are delayed in their development and fail to form normal anterior embryonic structures. They show both an increase in programmed cell death and a decrease in mitotic index, especially in the region of the distal tip of the embryonic ectoderm. They also show a reduction in apical vacuoles in the columnar visceral endoderm cells in the extraembryonic region. Knockout mice die by 8 to 9 days of gestation.|||Nucleus http://togogenome.org/gene/10090:Or6c76 ^@ http://purl.uniprot.org/uniprot/Q8VEX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5p80 ^@ http://purl.uniprot.org/uniprot/Q8VG42 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Or5w1b ^@ http://purl.uniprot.org/uniprot/Q7TR44 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Bcl9 ^@ http://purl.uniprot.org/uniprot/Q9D219 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BCL9 family.|||Binds to beta-catenin (CTNNB1), PYGO1 and PYGO2; the interaction with PYGO1 increases PYGO1 affinity to histone H3 methylated at 'Lys 4'.|||Nucleus|||Promotes beta-catenin's transcriptional activity. Involved in signal transduction through the Wnt pathway (By similarity). http://togogenome.org/gene/10090:Defa5 ^@ http://purl.uniprot.org/uniprot/L7N230 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Hemgn ^@ http://purl.uniprot.org/uniprot/Q9ERZ0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at 8.5 dpc in the blood islands of the yolk sac and in the circulating primitive blood cells. Expressed in the circulating blood cells at 9.5 dpc and 10.5 dpc. Detected in the developing hepatic primordia at 10.5 dpc. From 11.5 dpc to 14.5 dpc, exclusively expressed in the fetal liver.|||Expressed in hematopoietic precursor cells. Highly expressed in bone marrow, the red pulp of the spleen and round spermatids. Weakly expressed in peripheral blood cells.|||Nucleus|||Regulates the proliferation and differentiation of hematopoietic cells. Overexpression block the TPA-induced megakaryocytic differentiation in the K562 cell model. May also prevent cell apoptosis through the activation of the nuclear factor-kappa B (NF-kB) (By similarity). http://togogenome.org/gene/10090:Sap30 ^@ http://purl.uniprot.org/uniprot/O88574 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SAP30 family.|||Component of the histone deacetylase complex that includes at least SIN3A, HDAC1 and HDAC2 (PubMed:9702189). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (PubMed:28554894). Interacts with HDAC1 (PubMed:9702189). Interacts with SIN3A, SIN3B, HDAC2, RBBP4 and NCOR1 (PubMed:9702189). Interacts directly with SAMSN1 (PubMed:20478393). Interacts with HCFC1 (By similarity). Interacts with SAP30BP (By similarity).|||Involved in the functional recruitment of the Sin3-histone deacetylase complex (HDAC) to a specific subset of N-CoR corepressor complexes. Capable of transcription repression by N-CoR. Active in deacetylating core histone octamers (when in a complex) but inactive in deacetylating nucleosomal histones.|||Nucleus http://togogenome.org/gene/10090:Ffar3 ^@ http://purl.uniprot.org/uniprot/Q08AU6|||http://purl.uniprot.org/uniprot/Q3UFD7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in sympathetic ganglia and trunks at 13.5 dpc, 15.5 dpc and P1. Up-regulated during myocyte and adipocyte differentiation (at protein level).|||Expressed in white adipose tissue and skeletal muscle (at protein level). Abundantly expressed in sympathetic ganglia such as the superior cervical ganglion. Also expressed by intestinal endocrine cells.|||G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins. Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. Activated by SCFAs and by beta-hydroxybutyrate, a ketone body produced by the liver upon starvation, it inhibits N-type calcium channels and modulates the activity of sympathetic neurons through a signaling cascade involving the beta and gamma subunits of its coupled G protein, phospholipase C and MAP kinases. Thereby, it may regulate energy expenditure through the control of the sympathetic nervous system that controls for instance heart rate (PubMed:21518883, PubMed:22673524). Upon activation by SCFAs accumulating in the intestine, it may also signal to the brain via neural circuits which in turn would regulate intestinal gluconeogenesis. May also control the production of hormones involved in whole-body energy homeostasis. May for instance, regulate blood pressure through renin secretion (PubMed:23401498). May also regulate secretion of the PYY peptide by enteroendocrine cells and control gut motility, intestinal transit rate, and the harvesting of energy from SCFAs produced by gut microbiota (PubMed:18931303). May also indirectly regulate the production of LEP/Leptin, a hormone acting on the CNS to inhibit food intake, in response to the presence of short-chain fatty acids in the intestine (PubMed:14722361, PubMed:20399779). Finally, may also play a role in glucose homeostasis (PubMed:22190648, PubMed:24748202). Besides its role in energy homeostasis, may play a role in intestinal immunity. May mediate the activation of the inflammatory and immune response by SCFAs in the gut, regulating the rapid production of chemokines and cytokines by intestinal epithelial cells (PubMed:23665276). Exhibits an SCFA-independent constitutive G protein-coupled receptor activity (PubMed:23066016).|||Knockout mice display a retarded growth of sympathetic innervation and the superior cervical ganglion is significantly smaller. A heart rate decrease is also observed together with altered secretion of cardiac noradrenaline that might be due to reduced sympathetic nerve activity. Contrary to wild-type mice, oxygen consumption is not modified by feeding or starvation (PubMed:21518883). They also display impaired SCFA-triggered glucagon-like peptide 1/GLP-1 secretion and impaired glucose tolerance (PubMed:22190648). Finally, knockout mice display altered protective intestinal inflammatory and immune responses. Otherwise, they display normal growth and no major morphological abnormalities. Body weight, heart weight to body weight ratio, and metabolic parameters are comparable. However, there might be a gender bias, the effect on energy expenditure and body fat content being male specific (PubMed:23110765).|||Membrane http://togogenome.org/gene/10090:Or8k23 ^@ http://purl.uniprot.org/uniprot/A2AVY0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Msmp ^@ http://purl.uniprot.org/uniprot/B1AWI6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (By similarity). Exhibits a chemotactic activity for monocytes and lymphocytes but not neutrophils (By similarity).|||Belongs to the beta-microseminoprotein family.|||Secreted http://togogenome.org/gene/10090:Plrg1 ^@ http://purl.uniprot.org/uniprot/Q922V4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat PRL1/PRL2 family.|||Identified in the spliceosome C complex. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts (via its WD40 repeat domain) directly with CDC5L (via its C-terminal); the interaction is required for mRNA splicing but not for spliceosome assembly. Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with CRIPT (By similarity). Also interacts directly in the complex with BCAS2 and PRPF19. Interacts with USB1 (By similarity).|||Involved in pre-mRNA splicing as component of the spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Snrpg ^@ http://purl.uniprot.org/uniprot/P62309 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2. Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts with GEMIN2 (via N-terminus); the interaction is direct. Interacts with SNRPE; the interaction is direct.|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. IAs a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. As part of the U7 snRNP it is involved in histone 3'-end processing.|||cytosol http://togogenome.org/gene/10090:Gjc3 ^@ http://purl.uniprot.org/uniprot/Q921C1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family. Gamma-type subfamily.|||CNS specific. Expression is restricted to brain, spinal cord, and sciatic nerve.|||Cell membrane|||It is uncertain whether Met-1 or Met-12 is the initiator.|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Scgb2b11 ^@ http://purl.uniprot.org/uniprot/A0A087WR49 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Rnf185 ^@ http://purl.uniprot.org/uniprot/Q91YT2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination of BNIP1 (By similarity). Acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation (By similarity). Protects cells from ER stress-induced apoptosis (By similarity). Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway (By similarity). Also acts as a regulator of the innate antiviral response by catalyzing 'Lys-27'-linked polyubiquitination of CGAS, thereby promoting CGAS cyclic GMP-AMP synthase activity (PubMed:28273161). Preferentially associates with the E2 enzymes UBE2J1 and UBE2J2 (By similarity).|||Endoplasmic reticulum membrane|||Interacts with ATG5 and BNIP1.|||Mitochondrion outer membrane|||The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.|||Ubiquitously expressed with high expression in testis. http://togogenome.org/gene/10090:Txndc2 ^@ http://purl.uniprot.org/uniprot/Q6P902 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed during spermiogenesis, restricted to the postmeiotic phase of spermatogenesis. First detected in elongating spermatids tails during steps 9 and 10 and is prominent in this region during steps 11-16. Also weakly present in the cytoplasmic lobe of these spermatids. During the last steps of spermiogenesis (steps 17-19), it strongly diminishes in the tail but appears to increase or become concentrated in the shrinking cytoplasmic lobe. By the last step of spermiogenesis (late step 19), cytoplasmic localization is barely detectable in the resulting residual body but still detectable in the cytoplasmic droplet (at protein level). Detected in testis of pre-pubertal animals at very low level.|||Probably plays a regulatory role in sperm development. May participate in regulation of fibrous sheath (FS) assembly by supporting the formation of disulfide bonds during sperm tail morphogenesis. May also be required to rectify incorrect disulfide pairing and generate suitable pairs between the FS constituents. Can reduce disulfide bonds in vitro in the presence of NADP and thioredoxin reductase.|||Testis-specific. Strongly expressed in the testicular seminiferous tubules, mostly in the round spermatids. http://togogenome.org/gene/10090:Mrpl47 ^@ http://purl.uniprot.org/uniprot/Q8K2Y7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL29 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Flvcr2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0E9|||http://purl.uniprot.org/uniprot/Q3UL56|||http://purl.uniprot.org/uniprot/Q91X85 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Feline leukemia virus subgroup C receptor (TC 2.A.1.28.1) family.|||Cell membrane|||Detected in fetal chondrocytes and osteoclasts at 19 dpc and 21 dpc, respectively (at protein level).|||Endoplasmic reticulum membrane|||Expressed in renal collecting ducts and distal tubules and in placenta in late term (at protein level).|||Interacts with components of the electron transfer complexes III, IV and V including CYC1, NDUFA4, COX4I1, ATP5PD and ATP5F1C; these interactions occur in the absence of heme and are disrupted upon heme binding (PubMed:32973183). Interacts with ATP2A2; this interaction occurs in the absence of heme and promotes ATP2A2 proteasomal degradation; this complex is dissociated upon heme binding (PubMed:32973183). Interacts with HMOX1; this interaction is potentiated in the presence of heme (PubMed:32973183).|||Membrane|||Mitochondrion membrane|||Putative heme b importer/sensor involved in heme homeostasis in response to the metabolic state of the cell and to diet. May act as a sensor of cytosolic and/or mitochondrial heme levels to regulate mitochondrial respiration processes, ATP synthesis and thermogenesis. At low heme levels, interacts with components of electron transfer chain (ETC) complexes and ATP2A2, leading to ubiquitin-mediated degradation of ATP2A2 and inhibition of thermogenesis. Upon heme binding, dissociates from ETC complexes to allow switching from mitochondrial ATP synthesis to thermogenesis. Alternatively, in coordination with ATP2A2 may mediate calcium transport and signaling in response to heme.|||The N-terminus contains histidine-proline motifs involved in heme binding. Can bind 2 to 3 heme molecules. http://togogenome.org/gene/10090:Lrrtm3 ^@ http://purl.uniprot.org/uniprot/Q8BZ81 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LRRTM family.|||Cell membrane|||Expressed in neuronal tissues.|||May play a role in the development and maintenance of the vertebrate nervous system. Exhibits a limited synaptogenic activity in vitro, restricted to excitatory presynaptic differentiation (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Usp45 ^@ http://purl.uniprot.org/uniprot/Q8K387 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Catalyzes the deubiquitination of SPDL1 (By similarity). Plays a role in the repair of UV-induced DNA damage via deubiquitination of ERCC1, promoting its recruitment to DNA damage sites (By similarity). May be involved in the maintenance of photoreceptor function (PubMed:30573563). May play a role in normal retinal development (By similarity). Plays a role in cell migration (By similarity).|||Cytoplasm|||Interacts with ERCC1 (PubMed:25538220). The catalytically active form interacts with SPDL1 (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Mutant mice generated by CRISPR-Cas9-mediated gene editing show severely reduced scotopic and photopic responses and have significantly fewer green cone photoreceptors compared to wild-type animals.|||Nucleus|||Photoreceptor inner segment|||Retina. http://togogenome.org/gene/10090:Nkx6-1 ^@ http://purl.uniprot.org/uniprot/Q99MA9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Embryonic development of mutant mice is normal until 13.5 dpc. At this stage, the normal expansion of pancreatic beta cells does not occur. At 18.5 dpc, the numbers of beta cells is dramatically decreased and the pancreatic insulin content is only 2% of wild-type. No effect on the production of other pancreatic hormones, including glucagon, somatostatin and pancreatic polypeptide (PP) (PubMed:11076772). Simultaneous knockout of NKX6-1 and NKX2-2 results in the complete absence of insulin-expressing cells in the pancreas throughout development, and instead accumulation of incompletely differentiated beta cells, a phenotype not distinguable from the single NKX2-2 knockout (PubMed:11076772).|||Expressed by neuronal progenitor cells in discrete domains of the ventral neural tube (PubMed:10830170). In the pancreas, expressed exclusively in insulin-producing beta cells of the islets of Langerhans (at protein level) (PubMed:11076772).|||In the developing pancreas, detected as early as 10.5 dpc in the majority of epithelial cells. This broad expression pattern persists through 12.5 dpc. Around 13.5 dpc, with the start of the secondary transition, becomes restricted and by 15.5 dpc, exclusively detected in insulin-expressing beta cells and in some scattered ductal and periductal cells (at protein level).|||Nucleus|||The C-terminal domain contributes to sequence-specific DNA-binding.|||Transcription factor which binds to specific A/T-rich DNA sequences in the promoter regions of a number of genes. Required for the development of insulin-producing beta cells in the islets of Langerhans at the secondary transition (PubMed:11076772). Involved in transcriptional regulation of the insulin gene. Together with NKX2-2 and IRX3, restricts the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class II proteins of neuronal progenitor factors, which are induced by SHH signals. http://togogenome.org/gene/10090:Lgr4 ^@ http://purl.uniprot.org/uniprot/A2ARI4|||http://purl.uniprot.org/uniprot/Q8BZR7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||During limb development, at 14.5 dpc, expressed in the mesenchyme, but not in the overlying ectoderm of the limb bud. In developing lungs, at 14.5 dpc, expressed at low levels in both the epithelium and mesenchyme lineages.|||Expressed in a circadian manner in the liver.|||Membrane|||Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May also act as a receptor for norrin (NDP), such results however require additional confirmation in vivo. Required during spermatogenesis to activate the Wnt signaling pathway in peritubular myoid cells. Required for the maintenance of intestinal stem cells and Paneth cell differentiation in postnatal intestinal crypts. Acts as a regulator of bone formation and remodeling. Involved in kidney development; required for maintaining the ureteric bud in an undifferentiated state. Involved in the development of the anterior segment of the eye. Required during erythropoiesis. Also acts as a negative regulator of innate immunity by inhibiting TLR2/TLR4 associated pattern-recognition and pro-inflammatory cytokine production. Plays an important role in regulating the circadian rhythms of plasma lipids, partially through regulating the rhythmic expression of MTTP (PubMed:24353284). Required for proper development of GnRH neurons (gonadotropin-releasing hormone expressing neurons) that control the release of reproductive hormones from the pituitary gland (PubMed:32493844).|||Strong variations in phenotypes, probably depending on the strain background used in the different experiments. According to a first report done in a C57BL/6 background, mice show intra-uterine growth retardation leading to embryonic and perinatal lethality (PubMed:15192078). A lethal phenotype was confirmed by other groups. In some cases however, few mice survive until adulthood. Mice that survive show wide spectrum of anterior segment dysgenesis phenotypes, including microphthalmia, iris hypoplasia, irdiocorneal angle malformation, cornea dysgenesis and cataract (PubMed:18424556). Defects in osteoblast differentiation and mineralization during embryonic bone formation are also observed. Postnatal mice that survive show defects in bone remodeling (PubMed:19605502). According to other reports done in other strain backgrounds, mice do not die and display defects in the male reproductive tract during the postnatal period (PubMed:16406039, PubMed:17079737, PubMed:23533175). Mice also show small kidneys, in which the total number and density of the glomeruli are decreased (PubMed:16785743). The use of conditional knockouts, leads to defects in hair placode formation, possibly due to reduced keratinocyte migration (PubMed:17079737, PubMed:17850793). Decrease in epithelial cell proliferation and strong reduction in terminal differentiation of Paneth cells in postnatal intestinal crypts (PubMed:21508962, PubMed:23393138). Fetuses display transient anemia during midgestation and abnormal definitive erythropoiesis (PubMed:18955481). Mice are also more susceptible and have much higher mortality to lipopolysaccharide (LPS) stimulation due to over-activated innate immune response (PubMed:23589304). Conditional knockout of both Lgr4 and Lgr5 in the gut results in Wnt signaling inhibition and results in the rapid demise of intestinal crypts (PubMed:21727895). Simultaneous knockdown of LGR4, LGR5 and LGR6 results in developmental phenotypes, such as cleft palate and ankyloglossia, but not in tetra-amelia with lung agenesis (PubMed:29769720). http://togogenome.org/gene/10090:9930104L06Rik ^@ http://purl.uniprot.org/uniprot/Q499E6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with AFG2A, AFG2B and CINP. Does not associate with pre-60S ribosomal particles.|||Involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Acts together with AFG2A, AFG2B and CINP.|||Nucleus|||Phosphorylated on serines by CK2 kinase. http://togogenome.org/gene/10090:Cd164l2 ^@ http://purl.uniprot.org/uniprot/Q3TYL8|||http://purl.uniprot.org/uniprot/Q9D6W7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CD164 family.|||Membrane http://togogenome.org/gene/10090:Vill ^@ http://purl.uniprot.org/uniprot/G5E8C6|||http://purl.uniprot.org/uniprot/G5E8H0|||http://purl.uniprot.org/uniprot/Q91YD6 ^@ Developmental Stage|||Function|||Similarity ^@ Belongs to the villin/gelsolin family.|||Not detected in adult tissues. Expressed at low levels in early embryogenesis.|||Possible tumor suppressor. http://togogenome.org/gene/10090:Tlr2 ^@ http://purl.uniprot.org/uniprot/G3X8Y8|||http://purl.uniprot.org/uniprot/Q9QUN7 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with Staphylococcus aureus protein SSL3; this interaction inhibits TLR2-mediated cytokine production.|||Belongs to the Toll-like receptor family.|||Cell membrane|||Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity) (PubMed:15690042). May also promote apoptosis in response to lipoproteins (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (By similarity). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (PubMed:17486091). Acts as the major receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PhoS1 (pstS1), in conjunction with TLR1 and for some but not all lipoproteins CD14 and/or CD36. The lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Recombinant MPT83 from M.tuberculosis stimulates secretion of cytokines (TNF-alpha, IL-6 and IL-12p40) by mouse macrophage cell lines in a TLR2-dependent fashion, which leads to increased host innate immunity responses against the bacterium (PubMed:22174456). Lung macrophages which express low levels of TLR2 respond poorly to stimulation by M.tuberculosis LpqH (PubMed:19362712). Required for normal uptake of M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (PubMed:27220037). Interacts with TICAM2 (By similarity).|||Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.|||Detected in a macrophage cell line, smooth muscle, lung, spleen, thymus, brain and adipose tissue. Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and at lower levels in lung macrophages (at protein level) (PubMed:19362712).|||Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12.|||Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2.|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||Interacts with LY96, TLR1 and TLR6 (via extracellular domain). TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand (PubMed:19931471). The heterodimers form bigger oligomers in response to their corresponding ligands as well as further heterotypic associations with other receptors such as CD14 and/or CD36 (By similarity). Binds MYD88 (via TIR domain). Interacts with TICAM1 (By similarity). Interacts with CNPY3 (PubMed:18780723). Interacts with ATG16L1 (By similarity). Interacts with non-modified M.tuberculosis protein MPT83 (PubMed:22174456). Interacts with PPP1R11 (PubMed:27805901). Interacts with TIRAP (By similarity).|||Membrane|||Membrane raft|||Mutants succumb to Staphylococcus aureus infection within 5 days.|||The ATG16L1-binding motif mediates interaction with ATG16L1.|||Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation. Deubiquitinated by USP2.|||phagosome membrane http://togogenome.org/gene/10090:Nr2e1 ^@ http://purl.uniprot.org/uniprot/Q64104|||http://purl.uniprot.org/uniprot/Q78ZM1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Expressed in embryonic developing forebrain and in dorsal midbrain. Outside the neural epithelium only found in the surface ectoderm at the site of nasal placode formation, where subsequently the nasal and olfactory epithelium is formed. Also expressed in adult brain.|||Expression is first detected on 8 dpc and increases until 13.5 dpc, then sharply decreases from day 13 dpc until 18 dpc. Expression is barely detected in newborn brains but increases again after birth. Highly expressed in the retinal neuroblastic layer during the early stages of retinogenesis. Down-regulated during neuronal development. At 14.5 dpc, expressed in the periventricular neural stem cells of the brain.|||Mice show exhibit hyperaggressivity, decreased body fat and have ocular defects. Female mice lack maternal instincts. In developing brain, there are reduced areas of the ventricular zone and enlarged ventricles. Neuron progenitor cell divide more slowly. There is complete loss of visual acuity, with mice not being able to distinguish the cliff nor light and dark transition. There is a dramatic reduction in retina thickness and enhanced generation of S-cones with more differentiated neurons, fewer proliferation retinal progenitor cells (RPCs) and more cells undergoing apoptosis leading to progressive retinal dystrophy, optic nerve degradation and blindness.|||Monomer (By similarity). Interacts with ATN1; the interaction represses the transcription.|||Nucleus|||Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half-site sequence 5'-AAGGTCA-3' in which the 5' flanking nucleotides participate in determining receptor specificity (By similarity). Regulates cell cycle progression in neural stem cells of rhe developing brain. Involved in the regulation of retinal development and essential for vision. During retinogenesis, regulates PTEN-Cyclin D expression via binding to the promoter region of PTEN and suppressing its activity. May be involved in retinoic acid receptor (RAR) regulation in retinal cells. http://togogenome.org/gene/10090:Slc25a53 ^@ http://purl.uniprot.org/uniprot/A2AF28|||http://purl.uniprot.org/uniprot/E9PZF7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Membrane http://togogenome.org/gene/10090:Cyp2j6 ^@ http://purl.uniprot.org/uniprot/O54750|||http://purl.uniprot.org/uniprot/Q8CC91 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Edc3 ^@ http://purl.uniprot.org/uniprot/A0ELI5|||http://purl.uniprot.org/uniprot/Q8K2D3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EDC3 family.|||Binds single-stranded RNA. Involved in the process of mRNA degradation and in the positive regulation of mRNA decapping (By similarity).|||Homodimer (via YjeF N-terminal domain). Forms a complex with DCP1A, DCP2, DDX6 and EDC4/HEDLS, within this complex directly interacts with DCP1A and DDX6. Interacts with ZFP36.|||P-body|||The DFDF domain is unstructured by itself. It assumes a helical fold upon interaction with DDX6 (By similarity). http://togogenome.org/gene/10090:Prkar2b ^@ http://purl.uniprot.org/uniprot/P31324 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cAMP-dependent kinase regulatory chain family.|||Cell membrane|||Cytoplasm|||Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.|||Phosphorylated by the activated catalytic chain.|||Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.|||The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with PRKACA and PRKACB. Interacts with the phosphorylated form of PJA2. Forms a complex composed of PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity. http://togogenome.org/gene/10090:Rictor ^@ http://purl.uniprot.org/uniprot/Q6QI06 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RICTOR family.|||Highest levels in liver and brain with expression also detected in heart, muscle, spleen and kidney (at protein level).|||Mice develop normally until E9.5, and then display growth arrest and embryonic lethality by 11.5 dpc.|||Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15467718, PubMed:16962829, PubMed:16962653). Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to MTOR and PRR5 within the TORC2 complex; interaction with MTOR is enhanced by deubiquitination of RICTOR by USP9X. Interaction with MAPKAP1 is not enhanced by RICTOR deubiquitination by USP9X (By similarity). Interacts with CCDC28B. Interacts with NBN. Interacts with PRR5L (By similarity). Interacts with SIK3 (By similarity). Interacts with NCKAP1L (By similarity). Interacts with FBXW7; the interaction results in RICTOR ubiquitination and degradation (By similarity). Interacts with USP9X; the interaction results in deubiquitination of RICTOR and protection from proteasomal degradation, thus promoting mTORC2 complex assembly (By similarity). Interacts with ARMH4 (via cytoplasmic tail); this interaction bridges ARMH4 to the mTORC2 complex and inhibits the mTORC2 kinase activity (PubMed:25418727).|||Phosphorylated by MTOR; when part of mTORC2 (By similarity). Phosphorylated at Thr-1135 by RPS6KB1; phosphorylation of RICTOR inhibits mTORC2 and AKT1 signaling (By similarity).|||Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Plays an essential role in embryonic growth and development.|||Ubiquitinated by the SCF(FBXW7) complex, leading to its degradation by the proteasome (By similarity). Deubiquitinated by USP9X; deubiquitination stabilizes RICTOR and enhances its binding to MTOR, thus promoting mTORC2 complex assembly (By similarity). http://togogenome.org/gene/10090:Or4b1b ^@ http://purl.uniprot.org/uniprot/Q8VGN8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prss43 ^@ http://purl.uniprot.org/uniprot/Q76HL1 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||In testis, expressed at all stages from the late pachytene primary spermatocyte to the secondary spermatocyte. Not detected at day 7 after birth. Expression is detected at day 14 and increases dramatically at day 21 and reach a peak at day 28 to remain high until day 56.|||Lacks protease activity in vitro.|||Plays a role in spermatogenesis. Involved in germ cell survival during meiosis. Lacks protease activity in vitro.|||Testis-specific (PubMed:23536369). Expressed in germ cells at the stages from late pachytene spermatocytes to spermatids (PubMed:23536369). http://togogenome.org/gene/10090:Mfap3 ^@ http://purl.uniprot.org/uniprot/Q922T2 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Cell membrane|||Component of the elastin-associated microfibrils.|||Glycosylated. http://togogenome.org/gene/10090:Trim32 ^@ http://purl.uniprot.org/uniprot/Q3TLR3|||http://purl.uniprot.org/uniprot/Q8CH72 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||By interferon alpha/UVB treatment.|||Cytoplasm|||Has an E3 ubiquitin ligase activity (PubMed:14578165, PubMed:16816390). Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation (By similarity). May ubiquitinate BBS2 (By similarity). Ubiquitinates PIAS4/PIASY and promotes its degradation in keratinocytes treated with UVB and TNF-alpha (PubMed:14578165, PubMed:16816390)Also acts as a regulator of autophagy by mediating formation of unanchored 'Lys-63'-linked polyubiquitin chains that activate ULK1: interaction with AMBRA1 is required for ULK1 activation (By similarity).|||It self-associates (By similarity). Interacts with DTNBP1 (By similarity). Interacts with PIAS4/PIASY upon treatment with UVB and TNF-alpha (PubMed:16816390). Interacts with AMBRA1; promoting activation of ULK1 through unanchored 'Lys-63'-linked polyubiquitin chains (By similarity).|||Ubiquitinated.|||Ubiquitous. High expression in brain. http://togogenome.org/gene/10090:Abca14 ^@ http://purl.uniprot.org/uniprot/E9Q8F8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Vmn2r38 ^@ http://purl.uniprot.org/uniprot/G3UYA8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppargc1b ^@ http://purl.uniprot.org/uniprot/Q8VHJ7 ^@ Domain|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains 3 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which are usually required for the association with nuclear receptors.|||Induced by fasting in the liver, but not by cold exposure in brown adipose tissue. Induced also by saturated fatty acids in primary hepatocytes.|||Interacts with estrogen receptor alpha/ESR1 (By similarity). Interacts with hepatocyte nuclear factor 4-alpha/HNF4A, Sterol regulatory binding transcription factor 1/SREBF1, PPAR-alpha/PPARA, thyroid hormone receptor beta/THRB and host cell factor/HCFC1. Interacts with estrogen-related receptor gamma/ESRRG and alpha/ESRRA. Interacts with PRDM16.|||Nucleus|||Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be part of the pathways regulating the elevation of gluconeogenesis, beta-oxidation of fatty acids and ketogenesis during fasting. Stimulates SREBP-mediated lipogenic gene expression in the liver. Induces energy expenditure and antagonizes obesity when overexpressed. Induces also the expression of mitochondrial genes involved in oxidative metabolism. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner.|||Transgenic mice overexpressing PPARGC1B exhibits increased expression of medium-chain acyl CoA dehydrogenase. They are hyperphagic but lean, with increased energy expenditure and resistance to obesity.|||Ubiquitous with higher expression in heart, brown adipose tissue, brain and skeletal muscle. http://togogenome.org/gene/10090:Ptp4a1 ^@ http://purl.uniprot.org/uniprot/Q63739 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family.|||Cell membrane|||Cytoplasm|||Early endosome|||Endoplasmic reticulum|||Expressed in all tissues except heart and skeletal muscle, from 10.5 dpc to 18.5 dpc.|||Farnesylated. Farnesylation is required for membrane targeting. Unfarnesylated forms are shifted into the nucleus.|||Homotrimer. Interacts with tubulin (By similarity). Interacts with ATF5.|||Inhibited by sodium orthovanadate and pentamidine.|||Nucleus|||Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. May play a role in the development and maintenance of differentiating epithelial tissues (By similarity).|||spindle http://togogenome.org/gene/10090:Spata2 ^@ http://purl.uniprot.org/uniprot/Q8K004 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPATA2 family.|||Bridging factor that mediates the recruitment of CYLD to the LUBAC complex, thereby regulating TNF-alpha-induced necroptosis (By similarity). Acts as a direct binding intermediate that bridges RNF31/HOIP, the catalytic subunit of the LUBAC complex, and the deubiquitinase (CYLD), thereby recruiting CYLD to the TNF-R1 signaling complex (TNF-RSC) (By similarity). Required to activate the 'Met-1'- (linear) and 'Lys-63'-linked deubiquitinase activities of CYLD (PubMed:28701375). Controls the kinase activity of RIPK1 and TNF-alpha-induced necroptosis by promoting 'Met-1'-linked deubiquitination of RIPK1 by CYLD (PubMed:28701375).|||Cytoplasm|||Interacts (via the PIM motif) with RNF31/HOIP (via the PUB domain); the interaction is direct. Interacts (via the PUB domain) with CYLD; the interaction is direct.|||Mice are fertile and healthy with no obvious abnormalities in major organs in normal conditions (PubMed:29025062, PubMed:28701375). Males however display a decreased fertility: they show reduced testis size and sperm number (PubMed:29025062). The proliferation of germ cells in the seminiferous tubules is decreased in male gonads (PubMed:29025062). Impaired necroptosis: deficient cells show resistance to RIPK1-dependent apoptosis and necroptosis and are partially protected against RIPK1-independent apoptosis (PubMed:28701375).|||Nucleus|||Widely expressed, with highest expression in testis, lung and intestine, and lower expression in brain, heart and spleen (PubMed:28701375). Present at high level in Sertoli cells: expressed from stage I to stage XII of the testis seminiferous epithelium (at protein level) (PubMed:29025062). http://togogenome.org/gene/10090:Col4a1 ^@ http://purl.uniprot.org/uniprot/P02463 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain. NC1 domain mediates hexamerization of alpha chains of type IV collagen (PubMed:22842973).|||Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation.|||Belongs to the type IV collagen family.|||Contains 3-hydroxyproline. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.|||Contains 4-hydroxyproline. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Detected in the basement membrane of the cornea (at protein level).|||Insertion sequence.|||Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated. The modified lysines can be O-glycosylated.|||Mice develop perinatal cerebral hemorrhage and porencephaly. The mutant protein inhibits the secretion of mutant and normal proteins into the basement membrane of embryonic origin. The mutation is semidominant.|||Proteolytic processing produces the C-terminal NC1 peptide, arresten.|||The trimeric structure of the NC1 domains is stabilized by covalent bonds (sulfilimine cross-links) between Lys and Met residues. These cross-links are important for the mechanical stability of the basement membrane (PubMed:28424209, PubMed:22842973). Sulfilimine cross-link is catalyzed by PXDN (PubMed:22842973).|||There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. Interacts with EFEMP2 (PubMed:17324935).|||Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.|||Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.|||basement membrane http://togogenome.org/gene/10090:Oas1c ^@ http://purl.uniprot.org/uniprot/Q924S2 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Tissue Specificity ^@ Belongs to the 2-5A synthase family.|||By interferon (IFN) and polyinosinic:polycytidylic acid (poly I:C).|||Does not have 2'-5'-OAS activity, but can bind double-stranded RNA.|||Expressed at highest level in brain with lesser amounts in spleen, kidney, stomach, liver, intestine, ovary, skin and testis. Not detected in lung, thymus, heart and uterus.|||Expressed in embryonic stem cells and embryonic fibroblasts (PubMed:11418248). Detected 1 week after birth in developing ovary (PubMed:27663720). http://togogenome.org/gene/10090:Ptger3 ^@ http://purl.uniprot.org/uniprot/Q6PDF2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Clec4e ^@ http://purl.uniprot.org/uniprot/Q9R0Q8 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated molecular patterns (PAMPs) of bacteria and fungi (PubMed:18509109, PubMed:18490740, PubMed:18776906, PubMed:20008526, PubMed:19171887, PubMed:23602766). The PAMPs notably include mycobacterial trehalose 6,6'-dimycolate (TDM), a cell wall glycolipid with potent adjuvant immunomodulatory functions (PubMed:20008526, PubMed:23602766). Interacts with signaling adapter Fc receptor gamma chain/FCER1G to form a functional complex in myeloid cells (PubMed:23602766, PubMed:18776906). Binding of mycobacterial trehalose 6,6'-dimycolate (TDM) to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 (Th1) and T-helper 17 (Th17) cell subtypes (PubMed:23602766). Also recognizes alpha-mannose residues on pathogenic fungi of the genus Malassezia and mediates macrophage activation (PubMed:19171887). Through recognition of DAMPs released upon nonhomeostatic cell death, enables immune sensing of damaged self and promotes inflammatory cell infiltration into the damaged tissue (PubMed:18776906).|||Cell membrane|||Expression is induced upon exposure to bacterial glycolipids including lipopolysaccharide (LPS) and mycobacterial trehalose 6,6'-dimycolate (TDM) and several pro-inflammatory cytokines, including IFNG and TNF (PubMed:10528209, PubMed:23602766). Rapidly induced in thymus in response to whole-body irradiation and excessive cell death (PubMed:18776906). Induced in macrophages in response to C.albicans infection (PubMed:18490740).|||Highly expressed in macrophages in response to stimulation with bacterial glycolipids and pro-inflammatory cytokines (PubMed:10528209). Expressed in dendritic cells (at protein level) in response to stimulation with mycobacterial trehalose 6,6'-dimycolate (TDM) (PubMed:23602766).|||Knockout mice are born at the expected Mendelian rate (PubMed:19171887, PubMed:23602766). When compared to wild-type littermates, deficient mice show resistance to lethal systemic inflammation caused by exposure to mycobacterial cord factor/trehalose 6,6'-dimycolate (TDM) (PubMed:23602766). Mice are also susceptibility to systemic candidiasis (PubMed:18490740).|||Monomer and homodimer (PubMed:18509109). Interacts with signaling adapter Fc receptor gamma chain/FCER1G to form a functional complex; the interaction is direct (PubMed:23602766). Alternatively, acts as a bridge for interaction between CLEC4D and FCER1G. A heterodimer of CLEC4E and CLEC4D associates with FCER1G to form a functional complex (By similarity). Interacts with SAP130 nuclear protein that is released from necrotic cells; the interaction is direct (PubMed:23602766).|||phagocytic cup http://togogenome.org/gene/10090:Calm1 ^@ http://purl.uniprot.org/uniprot/P0DP26|||http://purl.uniprot.org/uniprot/P0DP27|||http://purl.uniprot.org/uniprot/P0DP28 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calmodulin family.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.|||Interacts with CEP97, CCP110, MYO1C, TTN/titin and SRY. Interacts with MYO10. Interacts with RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity). Interacts with RYR1 (PubMed:18650434). Interacts with MYO5A (By similarity). Interacts with IQCF1 (PubMed:25380116). Interacts with SYT7 (PubMed:24569478). Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity). Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434). Interacts with PCP4; regulates calmodulin calcium-binding (By similarity). Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (By similarity).|||Interacts with CEP97, CCP110, MYO1C, TTN/titin and SRY. Interacts with MYO10. Interacts with RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity). Interacts with RYR1 (PubMed:18650434). Interacts with MYO5A (PubMed:17151196). Interacts with IQCF1 (PubMed:25380116). Interacts with SYT7 (PubMed:24569478). Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity). Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434). Interacts with PCP4; regulates calmodulin calcium-binding (By similarity). Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (By similarity). Interacts with alpha-synuclein/SNCA (By similarity). Interacts with SLC9A1 in a calcium-dependent manner (By similarity). In the absence of Ca(+2), interacts with GIMAP4 (via IQ domain) (PubMed:16569770). Interacts with SCN8A; the interaction modulates the inactivation rate of SCN8A (PubMed:23942337). Interaction with KIF1A; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility (By similarity). Interacts with KCNN3 (By similarity). Interacts with KCNQ1 (via C-terminus); forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (By similarity). Interacts with PIK3C3; the interaction modulates PIK3C3 kinase activity (By similarity). Interacts with HINT1; interaction increases in the presence of calcium ions (PubMed:31088288). Interacts with HINT3 (PubMed:31088288). Interacts with GARIN2; in mature sperm flagella (PubMed:29025071). Interacts with IQUB (PubMed:36417862). Interacts with SLC26A5 (via STAS domain); this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).|||Phosphorylation results in a decreased activity.|||The N-terminal and C-terminal lobes of CALM bind to the C-terminus of KCNQ1 in a clamp-like conformation. Binding of CALM C-terminus to KCNQ1 is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to KCNQ1 is calcium-dependent and regulates electrophysiological activity of the channel.|||This protein has four functional calcium-binding sites.|||Ubiquitination results in a strongly decreased activity.|||centrosome|||flagellum|||spindle|||spindle pole http://togogenome.org/gene/10090:Cyp4a12a ^@ http://purl.uniprot.org/uniprot/Q91WL5 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of fatty acids and their oxygenated derivatives (oxylipins) (PubMed:17112342). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:17112342). Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of saturated and unsaturated fatty acids (PubMed:17112342). May act as a major omega-hydroxylase for dodecanoic (lauric) acid in kidney (PubMed:17112342). Participates in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure. Further catalyzes successive omega-oxidations of 20-HETE to the corresponding dicarboxylic acid, and may contribute to the degradation of PUFA by chain shortening (PubMed:17112342). Acts as an omega-hydroxylase and epoxidase toward (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoc acid (EPA). Catalyzes stereoselective epoxidation of the last double bond of EPA, displaying a strong preference for the (R,S) stereoisomer (PubMed:17112342). Can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of fatty acids with lower efficiency (PubMed:17112342).|||Activated by cytochrome b5. The Vmax almost doubles in the presence of cytochrome b5.|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Gender- and strain-specific expression in kidney (at protein level). Predominantly expressed in males, the expression among strains decreasing in the following order: NMRI > FVB/N > 129 Sv/J > Balb/c > C57BL/6. Expressed in renal arterioles.|||Microsome membrane|||Up-regulated by 5alpha-dihydrotestosterone. http://togogenome.org/gene/10090:Zmym5 ^@ http://purl.uniprot.org/uniprot/Q3U2E2 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Chimeric cDNA.|||Functions as a transcriptional regulator.|||Interacts (via N-terminal 120 amino acid region) with ETV5 (via C-terminal).|||Nucleus http://togogenome.org/gene/10090:Or7e176 ^@ http://purl.uniprot.org/uniprot/E9PVW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sdhaf1 ^@ http://purl.uniprot.org/uniprot/Q3U276 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I LYR family. SDHAF1 subfamily.|||Interacts with SDHB within an SDHA-SDHB subcomplex. Also interacts with the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20. Binding of SDHAF1 to SDHB precedes and is necessary for recruitment of the iron-sulfur transfer complex by SDHAF1.|||Mitochondrion matrix|||Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Promotes maturation of the iron-sulfur protein subunit Sdhb of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF3. Contributes to iron-sulfur cluster incorporation into SDHB by binding to SDHB and recruiting the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20. http://togogenome.org/gene/10090:Tmed6 ^@ http://purl.uniprot.org/uniprot/Q9CQG0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the EMP24/GP25L family.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Slc25a11 ^@ http://purl.uniprot.org/uniprot/Q5SX53|||http://purl.uniprot.org/uniprot/Q9CR62 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Catalyzes the transport of 2-oxoglutarate (alpha-oxoglutarate) across the inner mitochondrial membrane in an electroneutral exchange for malate. Can also exchange 2-oxoglutarate for other dicarboxylic acids such as malonate, succinate, maleate and oxaloacetate, although with lower affinity. Contributes to several metabolic processes, including the malate-aspartate shuttle, the oxoglutarate/isocitrate shuttle, in gluconeogenesis from lactate, and in nitrogen metabolism (By similarity). Maintains mitochondrial fusion and fission events, and the organization and morphology of cristae (By similarity). Involved in the regulation of apoptosis (PubMed:21448454). Helps protect from cytotoxic-induced apoptosis by modulating glutathione levels in mitochondria (By similarity).|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:P3h3 ^@ http://purl.uniprot.org/uniprot/Q8CG70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the leprecan family.|||Detected in kidney (at protein level).|||Endoplasmic reticulum|||Identified in a complex with PLOD1 and P3H4.|||No visible phenotype at birth. Lysine hydroxylation of skin and bone collagen alpha chains is strongly reduced. In contrast, prolyl 3-hydroxylation is not affected, possibly due to complementation by other family members. Dorsal skin displays impaired packing of collagen fibrils, decreased skin tensile strength, and increased skin fragility. Likewise, mice deficient for both P3h3 and P3h4 display decreased lysine hydroxylation of collagen alpha chains, but normal collagen prolyl 3-hydroxylation.|||Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils (PubMed:27119146). Required for normal hydroxylation of lysine residues in type I collagen chains in skin, bone, tendon, aorta and cornea (PubMed:28115524). Required for normal skin stability via its role in hydroxylation of lysine residues in collagen alpha chains and in collagen fibril assembly (PubMed:27119146, PubMed:28115524). Apparently not required for normal prolyl 3-hydroxylation on collagen chains, possibly because it functions redundantly with other prolyl 3-hydroxylases (PubMed:28115524). http://togogenome.org/gene/10090:Pecr ^@ http://purl.uniprot.org/uniprot/Q99MZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Highly expressed in liver and kidney. Expressed at lowe level in heart and skeletal muscle. Expressed at weak level in other tissues.|||Interacts with PEX5, probably required to target it into peroxisomes.|||Participates in chain elongation of fatty acids. Catalyzes the reduction of trans-2-enoyl-CoAs of varying chain lengths from 6:1 to 16:1, having maximum activity with 10:1 CoA. Has no 2,4-dienoyl-CoA reductase activity.|||Peroxisome http://togogenome.org/gene/10090:Krtap3-3 ^@ http://purl.uniprot.org/uniprot/Q9D638 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 3 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).|||Interacts with hair keratins. http://togogenome.org/gene/10090:Xrra1 ^@ http://purl.uniprot.org/uniprot/Q3U3V8 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||May be involved in the response of cells to X-ray radiation.|||Nucleus http://togogenome.org/gene/10090:Pcp4 ^@ http://purl.uniprot.org/uniprot/P63054 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the PCP4 family.|||Binds to both calcium-free and calcium-bound calmodulin. The affinity for the calcium-bound form is 50-fold greater.|||Functions as a modulator of calcium-binding by calmodulin. Thereby, regulates calmodulin activity and the different processes it controls. For instance, may play a role in neuronal differentiation through activation of calmodulin-dependent kinase signaling pathways.|||Mostly intrinsically disordered, with residual structure localized to the IQ domain which mediates the interaction with calmodulin. http://togogenome.org/gene/10090:Grap ^@ http://purl.uniprot.org/uniprot/Q9CX99 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates through its SH2 domain with ligand-activated receptors for stem cell factor (KIT) and erythropoietin (EPOR). Also forms a stable complex with the Bcr-Abl oncoprotein. GRAP is associated with the Ras guanine nucleotide exchange factor SOS1, primarily through its N-terminal SH3 domain. Interacts with phosphorylated LAT upon TCR activation. Interacts with SHB (By similarity).|||Belongs to the GRB2/sem-5/DRK family.|||Couples signals from receptor and cytoplasmic tyrosine kinases to the Ras signaling pathway. Plays a role in the inner ear and in hearing.|||Expressed in inner ear, in neruonal fibers innervating cochlear and utricular auditory hair cells (at protein level).|||Membrane|||Synapse http://togogenome.org/gene/10090:Cdc5l ^@ http://purl.uniprot.org/uniprot/Q3UCF2|||http://purl.uniprot.org/uniprot/Q6A068 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEF1 family.|||Cytoplasm|||DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Homodimer. Interacts with DAPK3 (By similarity). Component of the precatalytic, catalytic and postcatalytic spliceosome complexes (By similarity). Part of a spliceosomal 'core' complex consisting of CDC5L, PLRG1, SPF27, CCAP1, CCAP3 and CCAP6. Interacts with PLRG1, Lodestar/TTF2, and NIPP1/PPP1R8. Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with SCNM1 (By similarity). Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts (via its C-terminus) directly in the complex with PRPF19 and BCAS2. Interacts (via its C-terminus) directly with PRGL1 (via its WD40 repeat domain); the interaction is required for mRNA splicing but not for spliceosome assembly. Also interacts with CTNNBL1. Interacts with PRPF19 (via N-terminus) (By similarity). Interacts with USB1 (By similarity).|||Nucleus|||Nucleus speckle|||Phosphorylated on serine and threonine residues. Phosphorylation on Thr-411 and Thr-438 is required for CDC5L-mediated mRNA splicing. Has no effect on subcellular location nor on homodimerization. Phosphorylated in vitro by CDK2. Phosphorylation enhances interaction with PPP1R8. http://togogenome.org/gene/10090:Pde4a ^@ http://purl.uniprot.org/uniprot/B2RTL2|||http://purl.uniprot.org/uniprot/O89084|||http://purl.uniprot.org/uniprot/Q3TUD0 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.|||Binds 2 divalent metal cations per subunit (By similarity). Site 2 has a preference for magnesium and/or manganese ions (By similarity).|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Efficiently hydrolyzes cAMP.|||Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes.|||Inhibited by rolipram and diazepam.|||Interacts with LYN (via SH3 domain). Interacts with ARRB2.|||Membrane|||Proteolytically cleaved by CASP3.|||cytosol http://togogenome.org/gene/10090:Tdpoz5 ^@ http://purl.uniprot.org/uniprot/E0CYU8|||http://purl.uniprot.org/uniprot/Q2NL42 ^@ Similarity ^@ Belongs to the Tdpoz family. http://togogenome.org/gene/10090:Vmn1r21 ^@ http://purl.uniprot.org/uniprot/Q8R2C6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Eftud2 ^@ http://purl.uniprot.org/uniprot/A2AH85|||http://purl.uniprot.org/uniprot/O08810|||http://purl.uniprot.org/uniprot/Q543F1 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.|||Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (By similarity). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39 (By similarity). Component of the pre-catalytic, catalytic and post-catalytic spliceosome complexes (By similarity). Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with CRIPT (By similarity). Interacts with ERBB4 and PRPF8 (By similarity). Interacts with PIH1D1 (By similarity). Interacts with RPAP3 and URI1 in a ZNHIT2-dependent manner (By similarity). Interacts with NRDE2 (By similarity). Interacts with FAM50A (By similarity). Interacts with UBL5 (By similarity).|||Contaminating sequence. Vector contamination at the N-terminus.|||Nucleus|||Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes (By similarity). Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (By similarity). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). http://togogenome.org/gene/10090:Haspin ^@ http://purl.uniprot.org/uniprot/A0A0R4J0P2|||http://purl.uniprot.org/uniprot/Q9Z0R0 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylated on both serine and threonine residues (By similarity). Strongly phosphorylated during mitosis but this does not appear to significantly affect its intrinsic kinase activity. Phosphorylation by AURKB is required for full activity toward histone H3 at 'Ser-3' in mitosis (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Haspin subfamily.|||Chromosome|||Constitutive activity that does not require phosphorylation. Specifically inhibited by 3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine (CHR-6494).|||Expressed in germ cells within the testis of adults and of embryos from day 24 onwards. Also present in adult thymus and weakly expressed in spleen, lung and whole embryo.|||Nucleus|||Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle.|||spindle http://togogenome.org/gene/10090:Terf1 ^@ http://purl.uniprot.org/uniprot/P70371|||http://purl.uniprot.org/uniprot/Q3V252 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylation by TNKS1 or TNKS2 diminishes its ability to bind to telomeric DNA.|||Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.|||Binds the telomeric double-stranded 5'-TTAGGG-3' repeat.|||Homodimer.|||Homodimer; can contain both isoforms. Found in a complex with POT1; TINF2 and TNKS1. Interacts with ATM, TINF2, TNKS1, TNKS2, PINX1, NEK2 and MAPRE1. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Interacts with RLIM (via N-terminus). Interacts with FBXO4. Interaction with TINF2 protects against interaction with FBXO4 and subsequent polyubiquitination and proteasomal degradation (By similarity). Interacts with GNL3L; this interaction promotes homodimerization. Interacts with TIN2. Interactions with GNL3L and TIN2 are mutually exclusive. Interacts with RTEL1 (By similarity). Interacts with CCDC79/TERB1.|||Nucleus|||Phosphorylated preferentially on Ser-219 in an ATM-dependent manner in response to ionizing DNA damage.|||The HTH domain is an independent structural unit and mediates binding to telomeric DNA.|||The TRFH dimerization region mediates the interaction with TINF2.|||The acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules (By similarity).|||Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex, leading to its degradation by the proteasome (By similarity).|||spindle|||telomere http://togogenome.org/gene/10090:Vmn2r73 ^@ http://purl.uniprot.org/uniprot/D3Z7M3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mup5 ^@ http://purl.uniprot.org/uniprot/P11591 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Major urinary proteins (Mups) bind pheromones, and thus stabilize them to allow slow release into the air from urine marks. May protect pheromones from oxidation. May also act as pheromones themselves. In this context, they play a role in the regulation of social behaviors, such as aggression, mating, pup-suckling, territory establishment and dominance.|||Secreted http://togogenome.org/gene/10090:Adam26b ^@ http://purl.uniprot.org/uniprot/Q6IMH6|||http://purl.uniprot.org/uniprot/Q9CUI8 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Or52e4 ^@ http://purl.uniprot.org/uniprot/Q8VF06 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Acap1 ^@ http://purl.uniprot.org/uniprot/Q8K2H4 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Banana-shaped homodimer laterally assembling into tetramers, the tetramers further pack helically onto the membrane. Interacts with GTP-bound ARF6. Interacts with third cytoplasmic loop of SLC2A4/GLUT4. Interacts with CLTC. Interacts with GULP1. Forms a complex with GDP-bound ARF6 and GULP1. Interacts with ITGB1; required for ITGB1 recycling.|||Cells overexpressing Acap1 show accumulation of an electron dense coat containing Acap1 and Cltc on internal membranes as well as accumulation of Tfrc in pericentriolar recycling endosomes. Adipocytes with reduced level of Acap1 or Cltc fail to transport SLC2A4/GLUT4 from recycling endosomes to the cell surface upon insulin stimulation.|||GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.|||GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6) required for clathrin-dependent export of proteins from recycling endosomes to trans-Golgi network and cell surface. Required for regulated export of ITGB1 from recycling endosomes to the cell surface and ITGB1-dependent cell migration (By similarity).|||PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate ACAP1-binding to PIP2 or PIP3 containing membranes. Only one PH domain of one ACAP1 dimer inserts into the membrane, while the other PH domain acts primaryly to interact with adjacent ACAP1 dimers (By similarity).|||Recycling endosome membrane|||The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions (By similarity). http://togogenome.org/gene/10090:Aurkc ^@ http://purl.uniprot.org/uniprot/E9QL04|||http://purl.uniprot.org/uniprot/O88445|||http://purl.uniprot.org/uniprot/Q497X5 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.|||Chromosome|||Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; predominantly independent AURKB- and AURKC-containing complexes exist; in the complex interacts directly with BIRC5/survivin and INCENP. Interacts with TACC1.|||Expressed on day 14 dpc in prepubertal testis, expression reached its plateau on day 21 dpc and remained at a high level in adult.|||Expressed only in testis.|||Nucleus|||Okadaic acid, an inhibitor of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein phosphatase 5 (PP5), increases AURKC activity. AURKC is also stabilized through its interaction with INCENP, which acts also as an activator (By similarity).|||Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Also plays a role in meiosis and more particularly in spermatogenesis. Has redundant cellular functions with AURKB and can rescue an AURKB knockdown. Like AURKB, AURKC phosphorylates histone H3 at 'Ser-10' and 'Ser-28'. AURKC phosphorylates the CPC complex subunits BIRC5/survivin and INCENP leading to increased AURKC activity. Phosphorylates TACC1, another protein involved in cell division, at 'Ser-228'.|||centromere|||spindle http://togogenome.org/gene/10090:Slc12a5 ^@ http://purl.uniprot.org/uniprot/A0A076FSX1|||http://purl.uniprot.org/uniprot/Q91V14 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLC12A transporter family.|||Cell membrane|||Death at birth due to severe motor deficits including respiratory failure.|||Expressed in brainstem and spinal cord of 17 dpc embryos. Expressed in all parts of the brain and spinal cord in postnatal day 14 mice.|||Expressed in brainstem, spinal cord and olfactory bulb of 17 dpc embryos. Expressed in all parts of the brain and spinal cord in postnatal day 14 mice.|||Homodimer (PubMed:33597714). Heteromultimer with other K-Cl cotransporters (By similarity). Interacts with AP2A1 (PubMed:18625303).|||Inhibited following phosphorylation by OXSR1/OSR1 and STK39/SPAK: phosphorylation takes place downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4) in response to hyperosmotic stress and subsequent cell shrinkage.|||Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (By similarity). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (By similarity).|||Membrane|||Mice lacking isoform 2 die within 2 weeks after birth.|||Phosphorylated at Thr-929 and Thr-1029 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity.|||Predominant isoform during postnatal development. Detected in the ventral horns of the spinal cord at 12.5 dpc, and throughout the spinal cord at birth.|||Predominant isoform in 17 dpc brain.|||dendrite http://togogenome.org/gene/10090:Ddb2 ^@ http://purl.uniprot.org/uniprot/Q99J79 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated. Deacetylation by SIRT6 in response to UV stress facilitates nucleotide excision repair pathway (the NER pathway) transduction.|||Belongs to the WD repeat DDB2/WDR76 family.|||Chromosome|||Component of the UV-DDB complex which includes DDB1 and DDB2. The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit. Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1), which includes CUL4A or CUL4B, DDB1, DDB2 and RBX1. DDB2 may function as the substrate recognition module within this complex. The DDB1-CUL4-ROC1 complex may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. A large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces DDB2. These targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins (By similarity).|||Expressed in bone marrow, liver, lung, muscle, pancreas and spleen.|||Interblade loops of the WD repeat region mediate most of the interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA minor groove and mediates recognition of lesions and separation of the damaged and undamaged strands (By similarity).|||Mice exhibit elevated susceptibility to UV-induced skin carcinogenesis and enhanced rates of spontaneous tumor formation, particularly for lung and mammary adenocarcinomas. DDB2 is haploinsufficient as a tumor suppressor. The spleens of these animals are enlarged due to enhanced lymphoid proliferation while the testes are also enlarged due to reduced rates of apoptosis of testicular germ cells. Fibroblasts from these animals are resistant to p53-dependent apoptosis induced by UV treatment.|||Nucleus|||Phosphorylation by ABL1 negatively regulate UV-DDB activity.|||Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:12107171). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:33937266). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (By similarity). Also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1) (By similarity). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (By similarity). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (By similarity). The DDB2-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (By similarity). The DDB2-CUL4-ROC1 complex also ubiquitinates KAT7/HBO1 in response to DNA damage, leading to its degradation: recognizes KAT7/HBO1 following phosphorylation by ATR (By similarity).|||The DWD box is required for interaction with DDB1.|||Ubiquitinated by CUL4A in response to UV irradiation. Ubiquitination appears to both impair DNA-binding and promotes ubiquitin-dependent proteolysis. Degradation of DDB2 at sites of DNA damage may be a prerequisite for their recognition by XPC and subsequent repair. CUL4A-mediated degradation appears to be promoted by ABL1.|||Ubiquitinated, leading to proteasomal degradation, and deubiquitinated by USP24 (By similarity). Deubiquitinated by USP44; leading to its stabilization on DNA lesions (PubMed:33937266). http://togogenome.org/gene/10090:Or2ab1 ^@ http://purl.uniprot.org/uniprot/Q5NCC7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tcfl5 ^@ http://purl.uniprot.org/uniprot/Q32NY8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Arhgap24 ^@ http://purl.uniprot.org/uniprot/Q8C4V1 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell projection|||Interacts with FLNA.|||Phosphorylated by ROCK, leading to activate the RacGAP activity.|||Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis (By similarity).|||The coiled coil domain mediates the interaction with FLNA leading to its recruitment to lamellae.|||adherens junction|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Fancd2 ^@ http://purl.uniprot.org/uniprot/Q80V62 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts directly with FANCE and FANCI. Interacts with USP1 and MEN1. The ubiquitinated form specifically interacts with BRCA1 and BLM. Both the nonubiquitinated and the monoubiquitinated forms interact with BRCA2; this interaction is mediated by phosphorylated FANCG and the complex also includes XCCR3. The ubiquitinated form specifically interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to recruit MTMR15/FAN1 to sites of DNA damage. Interacts with DCLRE1B/Apollo. Interacts with POLN. Interacts with UHRF1 and UHRF2; these interactions promote FANCD2 activation.|||Mice display delayed pre- and postnatal development, defects in germ-cell development, and increase incidence of microphthalmia and tumors of epithelial cell origin.|||Monoubiquitinated on Lys-559 during S phase and upon genotoxic stress by FANCL in complex with E2 ligases UBE2T or UBE2W. Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the joint intervention of the FANC core complex, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM, and proteins involved in cell cycle checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1. Ubiquitination is required for binding to chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression (By similarity).|||Nucleus|||Phosphorylated on several sites including Ser-220 and Ser-1399 in response to genotoxic stress.|||Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (By similarity). Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. http://togogenome.org/gene/10090:Or8g35 ^@ http://purl.uniprot.org/uniprot/Q9EQ97 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fblim1 ^@ http://purl.uniprot.org/uniprot/Q71FD7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with FERMT2, FLNA, FLNB and FLNC (By similarity). Interacts with NKX2-5.|||Serves as an anchoring site for cell-ECM adhesion proteins and filamin-containing actin filaments. Is implicated in cell shape modulation (spreading) and motility. May participate in the regulation of filamin-mediated cross-linking and stabilization of actin filaments. May also regulate the assembly of filamin-containing signaling complexes that control actin assembly. Promotes dissociation of FLNA from ITGB3 and ITGB7. Promotes activation of integrins and regulates integrin-mediated cell-cell adhesion (By similarity).|||focal adhesion|||stress fiber http://togogenome.org/gene/10090:Ptger1 ^@ http://purl.uniprot.org/uniprot/B2RS62|||http://purl.uniprot.org/uniprot/P35375 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in kidney and in a lesser amount in lung.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Phosphorylated.|||Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues. http://togogenome.org/gene/10090:Muc15 ^@ http://purl.uniprot.org/uniprot/Q8C6Z1 ^@ PTM|||Subcellular Location Annotation ^@ Highly glycosylated (N- and O-linked carbohydrates).|||Membrane http://togogenome.org/gene/10090:Gatc ^@ http://purl.uniprot.org/uniprot/Q8CBY0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).|||Belongs to the GatC family.|||Mitochondrion|||Subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (GATB) and C (GATC) subunits. http://togogenome.org/gene/10090:Ccdc96 ^@ http://purl.uniprot.org/uniprot/Q9CR92 ^@ Subcellular Location Annotation ^@ centrosome http://togogenome.org/gene/10090:Rbpj ^@ http://purl.uniprot.org/uniprot/A0A0J9YTV5|||http://purl.uniprot.org/uniprot/E9Q7W0|||http://purl.uniprot.org/uniprot/P31266|||http://purl.uniprot.org/uniprot/Q3U6F1|||http://purl.uniprot.org/uniprot/Q3UM17 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Su(H) family.|||Cytoplasm|||Despite some similarity with the 'phage' integrase family, it has no recombinase activity.|||Interacts with RITA1, leading to nuclear export, prevent the interaction between RBPJ and NICD product and subsequent down-regulation of the Notch signaling pathway (By similarity). Interacts with activated NOTCH1, NOTCH2 and NOTCH3. Interacts with MINT/SHARP. This interaction may mediate the recruitment of large corepressor complexes containing proteins such as HDAC1, HDAC2, NCOR2, SAP30, FHL1/KYOT2 and CIR1. Interacts with EP300, MAML1 and PTF1A. Interacts with SNW1. Interacts with CHCHD2 and CXXC5. Interacts with BEND6 (via BEN domain) (By similarity). Interacts with NKAPL (PubMed:25875095). Interacts with ZMIZ1 (By similarity). Interacts with RBM15 (PubMed:17283045). Interacts with L3MBTL3; the interaction is impaired by Notch-derived peptides containing the intracellular domain (NICD) (PubMed:29030483). Interacts with KDM1A; the interaction with KDM1A is weaker in the absence of L3MBTL3 (By similarity).|||Nucleus|||Transcriptional regulator that plays a central role in Notch signaling, a signaling pathway involved in cell-cell communication that regulates a broad spectrum of cell-fate determinations (PubMed:7566092). Acts as a transcriptional repressor when it is not associated with Notch proteins. When associated with some NICD product of Notch proteins (Notch intracellular domain), it acts as a transcriptional activator that activates transcription of Notch target genes (By similarity) (PubMed:18381292). Probably represses or activates transcription via the recruitment of chromatin remodeling complexes containing histone deacetylase or histone acetylase proteins, respectively. Specifically binds to the immunoglobulin kappa-type J segment recombination signal sequence. Binds specifically to methylated DNA. Binds to the oxygen responsive element of COX4I2 and activates its transcription under hypoxia conditions (4% oxygen) (By similarity). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by repressing transcription of NADPH oxidase subunits (PubMed:26194095). http://togogenome.org/gene/10090:Ces2b ^@ http://purl.uniprot.org/uniprot/Q6PDB7 ^@ Similarity ^@ Belongs to the type-B carboxylesterase/lipase family. http://togogenome.org/gene/10090:Tmem213 ^@ http://purl.uniprot.org/uniprot/Q08EA8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Zfp93 ^@ http://purl.uniprot.org/uniprot/Q61116 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:L3mbtl4 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQK6|||http://purl.uniprot.org/uniprot/B1B1A0 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility (By similarity). http://togogenome.org/gene/10090:Igf2 ^@ http://purl.uniprot.org/uniprot/P09535 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8 dpc, 9.5 dpc and 16.5 dpc, transcripts from parental allele are detected in embryonic and extraembryonic tissues (PubMed:28522536, PubMed:1997210). At 16.5 dpc, transcripts from parental and maternal alleles are detected only in the choroid plexus and the leptomeninges (PubMed:1997210). Expressed in fetal muscle and brain tissue at 12.5 dpc (PubMed:29440408). Low levels of expression during myoblast proliferation. Levels rise rapidly during myoblast differentiation and then decrease.|||Belongs to the insulin family.|||Expressed in the heart, blood serum, kidney and skeletal muscle including the tibialis anterior muscle.|||Heterozygous animals are smaller than their wild type littermates but appear normal, reach sexual maturity and are fertile (PubMed:2330056). Transmission of this mutation through the male germline results in heterozygous progeny that are growth deficient. In contrast, when the disrupted gene is transmitted maternally, the heterozygous offspring are phenotypically normal. Homozygous mutants are indistinguishable in appearance from growth-deficient heterozygous siblings (PubMed:1997210). Mutant animals for transcript P0 specifically show a reduced growth of the placenta followed by fetal growth restriction, passive permeability for nutrients of the placenta is decreased (PubMed:12087403).|||Interacts with MYORG; this interaction is required for IGF2 secretion (PubMed:19706595). Interacts with integrins ITGAV:ITGB3 and ITGA6:ITGB4; integrin-binding is required for IGF2 signaling (By similarity).|||Predominant isoform expressed in fetal muscle tissues at 12.5 dpc.|||Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.|||Product of 4 different transcripts regulated by 4 different promoters, denominated P0, P1, P2 and P3.|||Proteolytically processed by PCSK4, proIGF2 is cleaved at Arg-128 and Arg-92 to generate big-IGF2 and mature IGF2.|||Secreted|||The IGF2 locus is imprinted. Paternal inherited gene is expressed, while the maternal inherited gene is imprinted, hence silenced (PubMed:1997210). It is differentially regulated in the placenta and fetus, transcribed from 3 promoters P1, P2 and P3 in both fetus and placenta and additionally from a fourth placental-specific promoter, P0 (Probable).|||The insulin-like growth factors possess growth-promoting activity (PubMed:29440408). Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development (Probable) (PubMed:2330056, PubMed:12087403). IGF2 is influenced by placental lactogen (Probable). Also involved in tissue differentiation (Probable). In adults, involved in glucose metabolism in adipose tissue, skeletal muscle and liver (Probable). Acts as a ligand for integrin which is required for IGF2 signaling (By similarity). Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation (PubMed:16901893). Inhibits myoblast differentiation and modulates metabolism via increasing the mitochondrial respiration rate (PubMed:32557799). http://togogenome.org/gene/10090:Kcnh1 ^@ http://purl.uniprot.org/uniprot/A0A1L1M1J8|||http://purl.uniprot.org/uniprot/Q3UHC9|||http://purl.uniprot.org/uniprot/Q60603 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv10.1/KCNH1 sub-subfamily.|||Cell membrane|||Channel activity is inhibited by interaction with Ca(2+)-bound calmodulin. Interaction of a single pore-forming alpha subunit with a calmodulin chain is sufficient to promote channel closure (By similarity). Channel activity is not regulated by cyclic nucleotides (PubMed:19671703). Channel activity is inhibited by binding intracellular phosphatidylinositol-3,5-bisphosphate and phosphatidylinositol-4,5-bisphosphate (PIP2), but is not inhibited by phosphatidylinositol 4-phosphate (By similarity).|||Channel activity is regulated via tyrosine phosphorylation/dephosphorylation by SRC and PTPN6.|||Detected in brain (at protein level) (PubMed:23424202, PubMed:25556795). Highly expressed in olfactory bulb. Detected in brain cortex, hippocampus, brain stem, striatum, thalamus, hypothalamus and spinal cord (PubMed:23424202).|||Early endosome membrane|||Membrane|||No visible phenotype. Mice are viable and fertile, and have normal brain morphology. Likewise, there is no change in the electrophysiological properties of cerebellar Purkinje cells and in the shape and frequency of action potentials.|||Nucleus inner membrane|||Perikaryon|||Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:19671703, PubMed:23975098). Channel properties are modulated by subunit assembly. Mediates IK(NI) current in myoblasts. Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (By similarity).|||Postsynaptic density membrane|||Presynaptic cell membrane|||The C-terminal region interacts with the cyclic nucleotide-binding domain and contributes to regulate channel gating.|||The PAS and PAC domain interact with the cyclic nucleotide-binding domain and contribute to the regulation of channel gating (PubMed:23975098). Calmodulin binding clamps together the PAS and PAC domain with the cyclic nucleotide-binding domain from a neighboring subunit and causes a conformation change that leads to channel closure.|||The cyclic nucleotide-binding domain lacks residues that are essential for nucleotide-binding and cannot bind cyclic nucleotides (PubMed:19671703). Instead, residues from the C-terminal domain (the so-called intrinsic ligand) bind in the cavity that would be expected to bind cyclic nucleotides. Interaction with the C-terminal region hinders interaction with CALM and reduces the affinity for CALM.|||The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Heteromultimer with KCNH5/EAG2 (By similarity). Interacts with ALG10B (By similarity). Interacts with RABEP1 (PubMed:22841712). Interacts (via C-terminus) with CTTN. Interacts (via C-terminal cytoplasmic region) with Ca(2+)-bound calmodulin (PubMed:27618660).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||axon|||dendrite http://togogenome.org/gene/10090:Arcn1 ^@ http://purl.uniprot.org/uniprot/Q5XJY5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adaptor complexes medium subunit family. Delta-COP subfamily.|||COPI-coated vesicle membrane|||Cytoplasm|||Golgi apparatus membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). http://togogenome.org/gene/10090:Or6c6c ^@ http://purl.uniprot.org/uniprot/Q7TRH7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mid1 ^@ http://purl.uniprot.org/uniprot/B1AV01|||http://purl.uniprot.org/uniprot/O70583 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||Expressed throughout embryonic development with highest levels from 7-11 dpc. Also expressed in the adult.|||Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.|||Homodimer or heterodimer with MID2. Interacts with IGBP1.|||Phosphorylated.|||Ubiquitously expressed in fetus and adult. At 9 dpc-10.5 dpc, highest expression found in frontonasal processes, branchial arches and CNS. From 12.5 dpc to 16.5 dpc, high levels found in rostral part of CNS. At 14.5 dpc, begins to be highly expressed in kidney and lung. At 16.5 dpc, highly expressed in the mucosa of the hindgut and cutaneous region of the stomach.|||cytoskeleton http://togogenome.org/gene/10090:Prl ^@ http://purl.uniprot.org/uniprot/Q3TT66|||http://purl.uniprot.org/uniprot/Q9CPQ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Astn2 ^@ http://purl.uniprot.org/uniprot/Q80Z10 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the astrotactin family.|||Cytoplasmic vesicle|||Detected at low levels in embryonic brain. Highly expressed 6 and 10 days after birth, when granule cell migration occurs in the cerebellum; expression in cerebellum is considerably higher than in brain cortex. Expressed at lower levels in adult cerebellum.|||Detected in cerebellum granule neurons; not detected in astroglia (at protein level). Detected primarily in cerebellum, and at lower levels in brain cortex, olfactory bulb, hindbrain and hippocampus dentate gyrus. Between 6 and 10 days after birth, when granule cell migration occurs in the cerebellum, detected in granule cell precursors in the external germinal layer, the molecular layer, the internal granule layer and in Purkinje neurons. Detected in postmitotic neurons in adult cerebellum.|||Early endosome|||Interacts with ASTN1; the interaction is not calcium-dependent.|||Late endosome|||Mediates recycling of the neuronal cell adhesion molecule ASTN1 to the anterior pole of the cell membrane in migrating neurons. Promotes ASTN1 internalization and intracellular transport of endocytosed ASTN1 (PubMed:20573900). Selectively binds inositol-4,5-bisphosphate, inositol-3,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate, suggesting it is recruited to membranes that contain lipids with a phosphoinositide headgroup (By similarity).|||Membrane|||Perikaryon|||The C-terminal region after the fibronectin type-III domain presents structural similarity to annexin domains and binds calcium ions.|||cell cortex|||clathrin-coated vesicle http://togogenome.org/gene/10090:Hpcal4 ^@ http://purl.uniprot.org/uniprot/Q8BGZ1 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the recoverin family.|||May be involved in the calcium-dependent regulation of rhodopsin phosphorylation.|||Probably binds two or three calcium ions. http://togogenome.org/gene/10090:Tmpo ^@ http://purl.uniprot.org/uniprot/Q3TNH0|||http://purl.uniprot.org/uniprot/Q61029|||http://purl.uniprot.org/uniprot/Q61033 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LEM family.|||Chromosome|||Citrullinated by PADI4.|||Has two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1 (By similarity).|||Homooligomer. Interacts with LMNA, BANF1 and RB1 and with chromosomes. Associates directly or indirectly with lamins at specific cell-cycle stages (By similarity). Interacts with CMTM6 (By similarity).|||Interacts with LMNB1, LMNB2, BANF1, AKAP8L, GMCL and chromosomes.|||May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1 (By similarity).|||May help direct the assembly of the nuclear lamina and thereby help maintain the structural organization of the nuclear envelope. Possible receptor for attachment of lamin filaments to the inner nuclear membrane. May be involved in the control of initiation of DNA replication through its interaction with NAKAP95 (By similarity).|||Mitosis-specific phosphorylation specifically abolishes its binding to lamin B and chromosomes.|||Nucleus|||Nucleus inner membrane|||Phosphorylated in a mitose-specific manner.|||The C-terminal domain forms a four-stranded coiled coil.|||The N-terminal part contains two structurally independent, non-interacting domains: LEM-like (also called LAP2-N or LEM-D) and LEM (also called LAP2-C or LEM-B). LEM-like binds DNA while LEM interacts with BANF1 (By similarity). http://togogenome.org/gene/10090:Commd10 ^@ http://purl.uniprot.org/uniprot/Q8JZY2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105, NFKB2/p100. Interacts with CCDC22, CCDC93, SCNN1B, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL7.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B.|||Nucleus http://togogenome.org/gene/10090:Trpd52l3 ^@ http://purl.uniprot.org/uniprot/Q9CQ14 ^@ Similarity ^@ Belongs to the TPD52 family. http://togogenome.org/gene/10090:Exosc2 ^@ http://purl.uniprot.org/uniprot/Q3TKQ3|||http://purl.uniprot.org/uniprot/Q8VBV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRP4 family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts with DIS3. Interacts with GTPBP1. Interacts with ZFP36L1 (via N-terminus).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC2 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC4 and EXOSC7 (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Scgb2b24 ^@ http://purl.uniprot.org/uniprot/D2XZ39|||http://purl.uniprot.org/uniprot/Q7M747 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the secretoglobin family.|||Expressed in lacrimal gland, at higher level in males than females.|||Secreted http://togogenome.org/gene/10090:Paqr4 ^@ http://purl.uniprot.org/uniprot/Q9JJE4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ADIPOR family.|||Membrane http://togogenome.org/gene/10090:Smn1 ^@ http://purl.uniprot.org/uniprot/P97801|||http://purl.uniprot.org/uniprot/Q549F9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMN family.|||Cajal body|||Cytoplasm|||Cytoplasmic granule|||Expressed in motor neurons.|||Homooligomer; may form higher order homooligomers in the dimer to octamer range. Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Component of an import snRNP complex composed of KPNB1, RNUT1, SMN1 and ZNF259. Interacts with DDX20, FBL, NOLA1, RNUT1 and with several spliceosomal snRNP core Sm proteins, including SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE and ILF3. Interacts with GEMIN2; the interaction is direct. Interacts with GEMIN3; the interaction is direct. Interacts with GEMIN8; the interaction is direct. Interacts with SNRPB; the interaction is direct. Interacts (via Tudor domain) with SNRPD1 (via C-terminus); the interaction is direct. Interacts with SNRPD2; the interaction is direct. Interacts (via Tudor domain) with SNRPD3 (via C-terminus); the interaction is direct. Interacts with SNRPE; the interaction is direct. Interacts with OSTF1, LSM10, LSM11 and RPP20/POP7. Interacts (via C-terminal region) with ZPR1 (via C-terminal region). Interacts (via Tudor domain) with COIL. Interacts with SETX; recruits SETX to POLR2A. Interacts with POLR2A (via the C-terminal domain (CTD)). Interacts with PRMT5. Interacts with XRN2. Interacts (via C-terminus) with FMR1 (via C-terminus); the interaction is direct and occurs in a RNA-independent manner (By similarity). Interacts with SYNCRIP (PubMed:11773003). Interacts (via Tudor domain) with SF3B2 (methylated form). Interacts with WRAP53/TCAB1 (By similarity). Interacts (via Tudor domain) with ELAVL4 in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules (By similarity). Interacts with GEMIN2; the interaction is direct (By similarity). Interacts with FRG1 (By similarity).|||Perikaryon|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Within the SMN complex, SMN1 acts as a structural backbone and together with GEMIN2 it gathers the Sm complex subunits (By similarity). Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development (PubMed:23063131). Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs) (By similarity).|||The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.|||Z line|||axon|||gem|||neuron projection http://togogenome.org/gene/10090:Alg1 ^@ http://purl.uniprot.org/uniprot/Q921Q3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 33 subfamily.|||Catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Cryz ^@ http://purl.uniprot.org/uniprot/P47199 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.|||Cytoplasm|||Does not have alcohol dehydrogenase activity. Binds NADP and acts through a one-electron transfer process. Orthoquinones, such as 1,2-naphthoquinone or 9,10-phenanthrenequinone, are the best substrates (in vitro). May act in the detoxification of xenobiotics. Interacts with (AU)-rich elements (ARE) in the 3'-UTR of target mRNA species and enhances their stability. NADPH binding interferes with mRNA binding (By similarity).|||Homotetramer. http://togogenome.org/gene/10090:A1cf ^@ http://purl.uniprot.org/uniprot/Q5YD48 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum|||Essential component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in APOB mRNA. Binds to APOB mRNA and is probably responsible for docking the catalytic subunit, APOBEC1, to the mRNA to allow it to deaminate its target cytosine. The complex also seems to protect the edited APOB mRNA from nonsense-mediated decay (By similarity).|||Expressed primarily in liver, small intestine and kidney.|||Mice display embryonic lethality at E3.5 due to failure of embryos to implant.|||Minor isoform detected in less than 10% of cDNA clones.|||Nucleus|||Part of the apolipoprotein B mRNA editing complex with APOBEC1. Interacts with TNPO2; TNPO2 may be responsible for transport of A1CF into the nucleus. Interacts with SYNCRIP. Interacts with CELF2/CUGBP2 (By similarity). Interacts with RBM47 (PubMed:24916387).|||The RRM domains are necessary but not sufficient for binding to APOB mRNA. Additional residues in the pre-RRM and C-terminal regions are required for RNA-binding and for complementing APOBEC1 activity (By similarity). http://togogenome.org/gene/10090:Gm773 ^@ http://purl.uniprot.org/uniprot/Q3TML4 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Selenow ^@ http://purl.uniprot.org/uniprot/P63300 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SelWTH family. Selenoprotein W subfamily.|||Cytoplasm|||Down-regulated by hydrogen peroxide. Increased levels are detected after treatment with L-buthionine sulfoxide (BSO) before exposure to hydrogen peroxide.|||Expression is first detected in the newly implanted embryo. Levels increase gradually during embryonic development with a steady increase during the second week and a dramatic increase by the end of gestation. Expression increases gradually in proliferating myotubes but is low in terminally differentiated myobutubes.|||In the embryo, expressed in the developing nervous system and in mesoderm-derived tissues such as heart and limbs. In the adult, predominantly expressed in brain, skeletal muscle and heart.|||Interacts with DPYSL2, PRDX1, YWHAB, YWHAG, HSP70 and HSP90.|||Plays a role as a glutathione (GSH)-dependent antioxidant. May be involved in a redox-related process. May play a role in the myopathies of selenium deficiency. http://togogenome.org/gene/10090:Ppip5k1 ^@ http://purl.uniprot.org/uniprot/A2ARP1 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the histidine acid phosphatase family. VIP1 subfamily.|||Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress.|||Cell membrane|||Intron retention.|||The C-terminal acid phosphatase-like domain binds PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity.|||cytosol http://togogenome.org/gene/10090:Or52b4 ^@ http://purl.uniprot.org/uniprot/E9PXN3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cpb1 ^@ http://purl.uniprot.org/uniprot/B2RS76 ^@ Similarity ^@ Belongs to the peptidase M14 family. http://togogenome.org/gene/10090:Mzt2 ^@ http://purl.uniprot.org/uniprot/Q9CQ25 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MOZART2 family.|||Part of the gamma-tubulin complex. Interacts with TUBG1.|||centrosome|||spindle http://togogenome.org/gene/10090:Tns4 ^@ http://purl.uniprot.org/uniprot/Q8BZ33 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PTEN phosphatase protein family.|||Interacts (via SH2 domain) with Rho GTPase-activating protein DLC1 (via C-terminus); the interaction is independent of DLC1 tyrosine phosphorylation. Interacts with integrin ITGB1; the interaction displaces tensin TNS3 from the ITGB1 cytoplasmic tail and promotes ITGB1 stability. Interacts (via SH2 domain) with E3 ubiquitin-protein ligase CBL (phosphorylated on 'Tyr-780'); the interaction is enhanced in the presence of EGF and reduces interaction of CBL with EGFR. Interacts (via SH2 domain) with receptor tyrosine kinase MET (when phosphorylated); the interaction increases MET protein stability.|||Promotes EGF-induced cell migration by displacing tensin TNS3 from the cytoplasmic tail of integrin ITGB1 which results in dissociation of TNS3 from focal adhesions, disassembly of actin stress fibers and initiation of cell migration. Suppresses ligand-induced degradation of EGFR by reducing EGFR ubiquitination in the presence of EGF. Increases MET protein stability by inhibiting MET endocytosis and subsequent lysosomal degradation which leads to increased cell survival, proliferation and migration.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Cnbd2 ^@ http://purl.uniprot.org/uniprot/Q9D5U8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Essential for male fertility. Plays an important role in spermatogenesis and regulates sperm motility by controlling the development of the flagellar bending of sperm (PubMed:24339785).|||Males are either infertile due to a lack of sperm resulting from spermatogenic arrest, or subfertile due to impaired sperm motility. The motility defect is caused by altered Ca(2+) regulation of the flagellar beat of sperm.|||Testis-specific. Exclusively expressed in testicular germ cells while it is not present in mature sperm (at protein level).|||cytosol http://togogenome.org/gene/10090:Vmn1r111 ^@ http://purl.uniprot.org/uniprot/D3YTY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ehbp1 ^@ http://purl.uniprot.org/uniprot/Q69ZW3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endosome|||Interacts with EHD1 (PubMed:15247266). Interacts with EHD2. Interacts with RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); at least in case of RAB8A may bind 2 molecules of RAB8A simultaneously through a high and a low affinity binding site, respectively (By similarity).|||May play a role in actin reorganization. Links clathrin-mediated endocytosis to the actin cytoskeleton. May act as Rab effector protein and play a role in vesicle trafficking (By similarity). Required for perinuclear sorting and insulin-regulated recycling of SLC2A4/GLUT4 in adipocytes.|||Membrane|||Prenylated (Probable). Farnelysation (predominant) and geranylgeranylation has been observed in vitro.|||The CAAX motif is a signal for prenylation and required for endosomal colocalization with Rab8 and Rab10.|||The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound form). http://togogenome.org/gene/10090:Crybb3 ^@ http://purl.uniprot.org/uniprot/Q9JJU9 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms (By similarity). http://togogenome.org/gene/10090:Bmf ^@ http://purl.uniprot.org/uniprot/Q91ZE9 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the Bcl-2 family.|||Interacts with MCL1, BCL2, BCL2L1/BCL-Xl, BCL2A1 and BCL2L2/BCL-w. Interacts with the myosin V actin motor complex through its binding to DLC2.|||May play a role in apoptosis.|||Widely expressed with an abundant expression in pancreas, liver kidney and hematopoietic tissues. http://togogenome.org/gene/10090:Slc2a6 ^@ http://purl.uniprot.org/uniprot/Q3UDF0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.|||Lysosome membrane|||Mainly expressed in brain and spleen (PubMed:29664675). Also expressed in lung, heart, muscle, liver, kidney, fat, whole blood, testes, ovaries and uterus (PubMed:29664675).|||Mild metabolic effects (PubMed:29664675, PubMed:30431159). Mice grow normally and glucose metabolism in male or female mice is normal (PubMed:29664675). Minimal metabolic effects are observed: female mice display a minor decrease in fat accumulation when fed Western diet and have a lower respiratory exchange ratio when fed chow diet (PubMed:29664675). Mice also exhibit a subtle phenotype in response to lipopolysaccharide administration, characterized by slight changes in the metabolome associated with glycolysis (PubMed:30431159).|||Probable sugar transporter that acts as a regulator of glycolysis in macrophages (PubMed:30431159). Does not transport glucose (By similarity). http://togogenome.org/gene/10090:Slc30a9 ^@ http://purl.uniprot.org/uniprot/F8WHL1|||http://purl.uniprot.org/uniprot/Q5IRJ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a zinc transporter involved in intracellular zinc homeostasis (By similarity). Functions as a secondary coactivator for nuclear receptors by cooperating with p160 coactivators subtypes (PubMed:15988012). Plays a role in transcriptional activation of Wnt-responsive genes (PubMed:17344318).|||Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Endoplasmic reticulum|||Interacts with GRIP1, ESR1, AR and CTNNB1.|||Membrane|||Mitochondrial proton-coupled zinc ion antiporter mediating the export of zinc from the mitochondria and involved in zinc homeostasis, zinc mobilization as well as mitochondrial morphology and health (By similarity). In nucleus, functions as a secondary coactivator for nuclear receptors by cooperating with p160 coactivators subtypes. Plays a role in transcriptional activation of Wnt-responsive genes (PubMed:15988012, PubMed:17344318).|||Mitochondrion membrane|||Nucleus http://togogenome.org/gene/10090:Or1p1c ^@ http://purl.uniprot.org/uniprot/Q7TRX0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp7b ^@ http://purl.uniprot.org/uniprot/Q64446 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.|||Copper ion transmembrane transporter involved in the export of copper out of the cells, such as the efflux of hepatic copper into the bile.|||Defects in Atp7b are the cause of the toxic milk mouse mutant (tx) phenotype, characterized by accumulation of copper in the liver in a manner similar to that observed in patients with Wilson disease.|||Detected in liver and kidney.|||Each HMA domain can bind a copper ion, they are tightly packed and closely interact with each other. Wild-type ATP7B can usually be loaded with an average 5.5 copper atoms per molecule (By similarity).|||Late endosome|||Monomer. Interacts with COMMD1/MURR1 (By similarity). Interacts with DCTN4, in a copper-dependent manner (By similarity). Interacts with ATOX1 (By similarity). Interacts (via C-terminus) with ZBTB16/PLZF (By similarity).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gckr ^@ http://purl.uniprot.org/uniprot/Q91X44 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GCKR family.|||Cytoplasm|||Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site.|||Interacts (fructose 6-phosphate bound form) with GCK.|||Mice appear normal and are fertile (PubMed:10713097). Their body weights do not differ significantly from the body weights of wild-type animals up to 60 weeks of age (PubMed:10713097). Mice however show a substantial decrease in hepatic glucokinase (Gck) expression and enzymatic activity, with no change in basal blood glucose levels (PubMed:10713097). However, following a glucose tolerance test, mice show impaired glucose clearance, possibly because they cannot recruit sufficient glucokinase due to the absence of a nuclear reserve (PubMed:10713097).|||Mitochondrion|||Nucleus|||Regulates glucokinase (GCK) by forming an inactive complex with this enzyme (PubMed:10713097). Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK that can be quickly released in the cytoplasm after a meal (PubMed:10713097). The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6-phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity (By similarity). http://togogenome.org/gene/10090:Tmsb15a ^@ http://purl.uniprot.org/uniprot/A2AEH9|||http://purl.uniprot.org/uniprot/Q9D2R9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thymosin beta family.|||Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Cacna1b ^@ http://purl.uniprot.org/uniprot/A2AIR9|||http://purl.uniprot.org/uniprot/A2AIS0|||http://purl.uniprot.org/uniprot/O55017 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.|||Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1B subfamily.|||Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.|||Is specifically blocked by omega-conotoxin GVIA (By similarity). Is specifically blocked by omega-conotoxin MVIIA (ziconotide) (By similarity). Is insensitive to dihydropyridines (DHP).|||Membrane|||Multisubunit complex consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interacts with RIMS1 (PubMed:11438518). Interacts with FMR1 (via C-terminus); this interaction induces a decrease in the number of presynaptic functional CACNA1B channels at the cell surface (PubMed:24709664).|||Phosphorylated in vitro by CaM-kinase II, PKA, PKC and CGPK.|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. Mediates Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity).|||Widespread expression throughout the brain. Highest levels in pyramidal cell layers C1, C2 and C3 of the hippocampus, in the dentate gyrus, in the cortex layers 2 et 4, in the subiculum and the habenula. http://togogenome.org/gene/10090:H2-M10.2 ^@ http://purl.uniprot.org/uniprot/Q85ZW9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Klf16 ^@ http://purl.uniprot.org/uniprot/P58334 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||High expression in brain; olfactory tubercle, olfactory bulb, nucleus accumbens, striatum, hippocampal CA1 region, amygdala, dentate gyrus and frontal cortex. Moderate expression in hippocampal CA2-3 regions, piriform cortex, septum, and distinct thalamic nuclei. Low expression in the cerebellum.|||Nucleus|||The Ala/Pro-rich domain may contain discrete activation and repression subdomains and also can mediate protein-protein interactions.|||Transcription factor that binds GC and GT boxes in the D1A, D2 and D3 dopamine receptor promoters and displaces Sp1 and Sp3 from these sequences. It modulates dopaminergic transmission in the brain by repressing or activating transcription from several different promoters depending on cellular context. http://togogenome.org/gene/10090:Golga4 ^@ http://purl.uniprot.org/uniprot/Q91VW5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Extended rod-like protein with coiled-coil domains.|||Golgi apparatus membrane|||Homodimer. Interacts with GTP-bound ARL1 and ARL3 (By similarity). Interacts with MACF1 (By similarity). Directly interacts with TBC1D23 (PubMed:29084197). Interacts with FAM91A1; this interaction may be mediated by TBC1D23 (By similarity).|||Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking.|||Ubiquitous. Highly expressed in oligodendrocyte precursors, particularly at a stage just prior to myelination.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Jun ^@ http://purl.uniprot.org/uniprot/P05627|||http://purl.uniprot.org/uniprot/Q52L79 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated at Lys-271 by EP300.|||Belongs to the bZIP family. Jun subfamily.|||Heterodimer with either BATF3 or ATF7 (By similarity). Heterodimer with FOS (PubMed:29272704). Heterodimer with FOSB isoform 1 and 2 (PubMed:29272704). Component of an AP-1 transcription factor complex composed of JUN-FOS heterodimers (PubMed:2498083). As part of the AP-1 transcription factor complex, forms heterodimers with FOSB, thereby binding to the AP-1 consensus sequence and stimulating transcription (PubMed:2498083). The ATF7/JUN heterodimer is essential for ATF7 transactivation activity. Interacts with SP1, SPIB and TCF20. Interacts with COPS5; the interaction leads indirectly to its phosphorylation. Component of the SMAD3/SMAD4/JUN/FOS/complex which forms at the AP1 promoter site. The SMAD3/SMAD4 heterodimer acts synergistically with the JUN/FOS heterodimer to activate transcription in response to TGF-beta (By similarity). Interacts (via its basic DNA binding and leucine zipper domains) with SMAD3 (via an N-terminal domain); the interaction is required for TGF-beta-mediated transactivation of the SMAD3/SMAD4/JUN/FOS/complex (By similarity). Interacts with TSC22D3 (via N-terminus); the interaction inhibits the binding of active AP1 to its target DNA (PubMed:11397794). Interacts with HIVEP3 and MYBBP1A (PubMed:9447996, PubMed:14707112). Interacts with methylated RNF187 (PubMed:20852630). Binds to HIPK3. Interacts (when phosphorylated) with FBXW7 (By similarity). Interacts with PRR7 (PubMed:27458189). Found in a complex with PRR7 and FBXW7 (By similarity). Interacts with PRR7 and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (By similarity). Interacts with RBM39 (PubMed:11704680). Interacts with PAGE4 (By similarity). Interacts with FOSL1 and FOSL2 (PubMed:29272704). Interacts with ARK2N and CSNK2B; the interaction with ARK2N is mediated by CSNK2B (By similarity).|||Nucleus|||Phosphorylated by CaMK4 and PRKDC; phosphorylation enhances the transcriptional activity. Phosphorylated by HIPK3. Phosphorylated by DYRK2 at Ser-246; this primes the protein for subsequent phosphorylation by GSK3B at Thr-242. Phosphorylated at Thr-242, Ser-246 and Ser-252 by GSK3B; phosphorylation reduces its ability to bind DNA. Phosphorylated by PAK2 at Thr-2, Thr-8, Thr-89, Thr-93 and Thr-289 thereby promoting JUN-mediated cell proliferation and transformation. Phosphorylated by PLK3 following hypoxia or UV irradiation, leading to increase DNA-binding activity (By similarity).|||Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:14707112). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription factor complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity (PubMed:2498083). Together with FOSB, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway (By similarity). Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation (PubMed:17210646). Involved in activated KRAS-mediated transcriptional activation of USP28 (By similarity). Binds to the USP28 promoter (By similarity).|||Ubiquitinated by the SCF(FBXW7), leading to its degradation. Ubiquitination takes place following phosphorylation, that promotes interaction with FBXW7. http://togogenome.org/gene/10090:Cep78 ^@ http://purl.uniprot.org/uniprot/Q6IRU7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CEP78 family.|||Expressed at all stages of development with higher expression during embryogenesis.|||Expressed by photoreceptor cells in the retina.|||Interacts with PLK4. Interacts with FAM161A.|||May be required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles. May play a role in cilium biogenesis.|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Aldh4a1 ^@ http://purl.uniprot.org/uniprot/Q8CHT0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-98, Lys-113 and Lys-401 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the aldehyde dehydrogenase family.|||Homodimer.|||Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes (By similarity).|||Mitochondrion matrix http://togogenome.org/gene/10090:Gpr101 ^@ http://purl.uniprot.org/uniprot/Q1WKE2|||http://purl.uniprot.org/uniprot/Q80T62 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the brain in hypothalamus.|||Membrane|||Orphan receptor. http://togogenome.org/gene/10090:Spopfm2 ^@ http://purl.uniprot.org/uniprot/Q3UTC4 ^@ Similarity ^@ Belongs to the Tdpoz family. http://togogenome.org/gene/10090:Btbd10 ^@ http://purl.uniprot.org/uniprot/E9Q6L8|||http://purl.uniprot.org/uniprot/E9Q6Y9|||http://purl.uniprot.org/uniprot/Q80X66 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts (via C-terminal 330-amino-acid region) with AKT1; AKT2 and AKT3 (PubMed:18160256). Interacts with PPP2CA and PPP1CA (PubMed:18160256).|||Nucleus|||Plays a major role as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, thereby keeping AKTs activated. Plays a role in preventing motor neuronal death and in accelerating the growth of pancreatic beta cells.|||Ubiquitously expressed (at protein level). http://togogenome.org/gene/10090:Igdcc4 ^@ http://purl.uniprot.org/uniprot/Q9EQS9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. DCC family.|||Cell membrane|||Expressed from 9.5 dpc. Expression is observed in the developing embryo, especially in the notochord, in developing skeletal muscles, and later in the ventricular zone of the nervous system.|||Expressed in skeletal muscle, heart and brain. Brain expression is hippocampus-specific. http://togogenome.org/gene/10090:Cenpk ^@ http://purl.uniprot.org/uniprot/A0A0R4J037|||http://purl.uniprot.org/uniprot/Q9ESN5 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CENP-K/MCM22 family.|||Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Acts in coordination with KNL1 to recruit the NDC80 complex to the outer kinetochore (By similarity).|||Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. May interact with Sox6.|||Contaminating sequence. Potential poly-A sequence.|||Highly expressed in testis.|||Nucleus|||centromere|||kinetochore http://togogenome.org/gene/10090:Grin3a ^@ http://purl.uniprot.org/uniprot/A2AIR5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR3A/GRIN3A subfamily.|||Cell membrane|||Expressed in the brain (at protein level).|||Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). Does not form functional homomeric channels. Found in a complex with GRIN1, GRIN2A or GRIN2B and PPP2CB. Probably interacts with PPP2CB. No complex with PPP2CB is detected when NMDARs are stimulated by NMDA (By similarity). Interacts (via C-terminus) with GIT1, but not with GRIA1/GluA1, nor with synaptophysin/SYP; this interaction competes with GIT1 interaction with ARHGEF7/beta-PIX (PubMed:24297929).|||NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. During the development of neural circuits, plays a role in the synaptic refinement period, restricting spine maturation and growth (By similarity). By competing with GIT1 interaction with ARHGEF7/beta-PIX, may reduce GIT1/ARHGEF7-regulated local activation of RAC1, hence affecting signaling and limiting the maturation and growth of inactive synapses (PubMed:24297929). May also play a role in PPP2CB-NMDAR mediated signaling mechanism (By similarity).|||Postsynaptic cell membrane|||Postsynaptic density http://togogenome.org/gene/10090:Etv4 ^@ http://purl.uniprot.org/uniprot/A2A5C2|||http://purl.uniprot.org/uniprot/A2A5C3|||http://purl.uniprot.org/uniprot/A6MDC6|||http://purl.uniprot.org/uniprot/P28322 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ETS family.|||Epididymis and brain.|||Nucleus|||Sumoylated; enhanced upon ERK/MAP kinase pathway activation it positively regulates the transcriptional activator capacity. Sumoylation at Lys-95 probably requires phosphorylation at Ser-100. Transiently polysumoylated and desumoylated by SENP1. Sumoylation is a prerequisite to polyubiquitination which in turn increases proteasomal-mediated degradation. Probably polyubiquitinated by RNF4 and deubiquitinated by USP2.|||Transcriptional activator (PubMed:1547944). May play a role in keratinocyte differentiation (By similarity). http://togogenome.org/gene/10090:Abl1 ^@ http://purl.uniprot.org/uniprot/P00520|||http://purl.uniprot.org/uniprot/Q3SYK5 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-710 by EP300 which promotes the cytoplasmic translocation.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily.|||Interacts with INPPL1/SHIP2. Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16. Interacts with the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN and YWHAZ; the interaction with 14-3-3 proteins requires phosphorylation on Thr-734 and sequesters ABL1 into the cytoplasm. Interacts (via SH3 domain) with CASP9; the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation (By similarity). Interacts with ABI1, ABI2, BCR, CRK, FYN, LYN, PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Interacts with STX17; probably phosphorylates STX17 (By similarity). Interacts with ITGB1, HCK and FGR. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity). Interacts with TBX21 (PubMed:21690296). Interacts with NEDD9/HEF1; interaction is induced by CXCL12 promotion of ABL-mediated phosphorylation of NEDD9/HEF1 (By similarity).|||Isoform IV is myristoylated on Gly-2.|||Mg(2+) and Mn(2+) were both present in the kinase buffer but Mg(2+) is likely to be the in vivo cofactor.|||Mitochondrion|||Mutants are born with the expected Mendelian frequency, but fail to thrive and most die within three weeks after birth. Most mutants are runted, and have atrophied thymuses with severe thymocyte deficiency. Mutants that survive to weaning age are most often runted, and about half of them show lymphopenia. They display a major reduction in the number of pre-B and immature B-cell classes in bone marrow with a wide variation between individuals, but essentially normal mature B-cell levels. Mutants are highly susceptible to infections. T-cells show impaired directional migration in response to the chemokines Cxcl12 or Ccl21 (PubMed:22810897). Abl1 and Abl2 double knockout mice have T-cells that show reduced chemokinesis and cell polarization in response to Icam1, Cxcl12 and Ccl21, subsequent Rap1 and Rac1 activation is reduced (PubMed:22810897). Additionally T-cells show decreased Cxcl12-induced tyrosine phosphorylation of Nedd9/Hef1 and reduced homing of T-cells to lymph nodes and immuno-challenged tissues (PubMed:22810897).|||Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (By similarity). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-191' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. Regulates T-cell differentiation in a TBX21-dependent manner (PubMed:21690296). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (PubMed:22810897). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (PubMed:21690296).|||Nucleus|||Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity (By similarity). Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity (By similarity). DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation. Phosphorylation at Thr-547 and Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division. Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1 (By similarity). Phosphorylation on Thr-734 is required for binding 14-3-3 proteins for cytoplasmic translocation (By similarity). Phosphorylated by PDGFRB and PRKDC.|||Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation (By similarity).|||Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation (By similarity). Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage (By similarity). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits also the tyrosine kinase activity. Inhibited by imatinib mesylate (Gleevec).|||Widely expressed.|||cytoskeleton http://togogenome.org/gene/10090:Rbpjl ^@ http://purl.uniprot.org/uniprot/O08674|||http://purl.uniprot.org/uniprot/Q3V2I2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Su(H) family.|||Highly expressed in lung. Also detected in spleen, and brain.|||Interacts weakly with EBNA2. Does not interact with any Notch proteins.|||Nucleus|||Putative transcription factor, which cooperates with EBNA2 to activate transcription. http://togogenome.org/gene/10090:Yrdc ^@ http://purl.uniprot.org/uniprot/Q3U5F4 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SUA5 family.|||By ischemia/reperfusion and endotoxemia.|||Cell membrane|||Cytoplasm|||Cytoplasmic and mitochondrial threonylcarbamoyl-AMP synthase required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. Catalyzes the conversion of L-threonine, HCO(3)(-)/CO(2) and ATP to give threonylcarbamoyl-AMP (TC-AMP) as the acyladenylate intermediate, with the release of diphosphate. Participates in t(6)A37 formation in cytoplasmic and mitochondrial tRNAs (By similarity). May regulate the activity of some transporters (PubMed:16024787).|||Interacts with RSC1A1.|||Mitochondrion|||The mitochondrial targeting sequence (MTS) is weak and only mediates import of a small fraction of YRDC in mitochondria.|||Widely expressed. Expressed at higher level in testis, secretory, and endocrine organs. http://togogenome.org/gene/10090:Raver2 ^@ http://purl.uniprot.org/uniprot/Q7TPD6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed throughout embryogenesis. Detected at low levels in adult lung, brain and kidney, but not in the other tissues tested.|||Interacts with PTBP1 and RAVER1.|||May bind single-stranded nucleic acids.|||Nucleus http://togogenome.org/gene/10090:Vmn1r206 ^@ http://purl.uniprot.org/uniprot/Q8R277 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Men1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1I3|||http://purl.uniprot.org/uniprot/O88559 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the MLL-HCF complex, at least composed of KMT2A/MLL1, MEN1, ASH2L, RBBP5, DPY30, WDR5, HCFC1 and HCFC2 (By similarity). Component of the menin-associated histone methyltransferase complex, at least composed of KMT2B/MLL4, MEN1, ASH2L, RBBP5, DPY30 and WDR5 (By similarity). Interacts with POLR2B (By similarity). Interacts with POLR2A phosphorylated at 'Ser-5', but not with the unphosphorylated, nor 'Ser-2' phosphorylated POLR2A forms (By similarity). Interacts with FANCD2 and DBF4 (By similarity). Interacts with SMAD3, but not with SMAD2, nor SMAD4 (By similarity). Directly interacts with NFKB1, NFKB2 and RELA (By similarity). Interacts with JUND (via MBM motif); inhibits the interaction of JUND with MAPK10 and the phosphorylation of JUND by MAP kinases MAPK8 and MAPK10 (PubMed:9989505). Interacts with KMT2A (via MBM motif) (By similarity). The KMT2A-MEN1 complex interacts with PSIP1 with a greater affinity as MEN1 enhances interaction of KMT2A with PSIP1 (By similarity).|||Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression (By similarity). May be involved in normal hematopoiesis through the activation of HOXA9 expression. May be involved in DNA repair.|||First detected at 7 dpc. At 13.5 dpc, expressed throughout the embryo, including forelimb, gut, head, heart and lung. At 17 dpc, expression becomes more restricted, with high levels mainly in the thymus, skeletal muscle, brain and spinal cord.|||Homozygous mice die in utero at 11.5-12.5 dpc. At 9 months of age, heterozygous mice develop pancreatic islet lesions, from hyperplasia to insulin-producing islet cell tumors, and frequently parathyroid adenomas. Larger, more numerous tumors involving pancreatic islets, parathyroids, thyroid, adrenal cortex and pituitary are seen by 16 months. All tumors show loss of the wild-type allele.|||Nucleus|||Widely expressed, with high levels in hippocampus, cerebral cortex, testis and thymus (at protein level). Also expressed at high levels in pancreatic islets, ovary and bone marrow. In the brain, highest expression in hippocampus pyramidal nerve cells (at protein level). In the testis, may be expressed in spermatogonia (at protein level). Low expression, if any, in skeletal muscle. http://togogenome.org/gene/10090:Lamb2 ^@ http://purl.uniprot.org/uniprot/Q3USI2|||http://purl.uniprot.org/uniprot/Q61292 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Domains VI and IV are globular.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Beta-2 is a subunit of laminin-3 (laminin-121 or S-laminin), laminin-4 (laminin-221 or S-merosin), laminin-7 (laminin-321 or KS-laminin), laminin-9 (laminin-421), laminin-11 (laminin-521), laminin-14 (laminin-423) and laminin-15 (laminin-523).|||Laminin-3 (S-laminin) regulates the formation of motor nerve terminals.|||Membrane|||Neuromuscular synapse and kidney glomerulus.|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Pde4c ^@ http://purl.uniprot.org/uniprot/Q3UEI1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.|||Binds 2 divalent metal cations per subunit (By similarity). Site 2 has a preference for magnesium and/or manganese ions (By similarity).|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.|||Part of a complex containing AKAP5, ADCY5, ADCY6 and PKD2.|||cilium http://togogenome.org/gene/10090:Jmjd7 ^@ http://purl.uniprot.org/uniprot/P0C872 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Bifunctional enzyme that acts both as an endopeptidase and 2-oxoglutarate-dependent monooxygenase (PubMed:28847961) (By similarity). Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation (PubMed:28847961). Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity (PubMed:28847961). Additionally, may play a role in protein biosynthesis by modifying the translation machinery. Acts as Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (S)-stereospecific hydroxylation at C-3 of 'Lys-22' of DRG1 and 'Lys-21' of DRG2 translation factors (TRAFAC), promoting their interaction with ribonucleic acids (RNA) (By similarity).|||Cytoplasm|||Homodimer; disulfide-linked. Interacts with DRG1 and DRG2.|||Nucleus|||This sequence was first thought to be an alternatively spliced isoform of Pla2g4b. It is derived from Jmjd7 which is located upstream of Pla2g4b. Most tissues also express read-through transcripts from Jmjd7 into the downstream Pla2g4b gene, some of which may encode fusion proteins combining the N-terminus of this protein with PLA2G4B protein. http://togogenome.org/gene/10090:Nup107 ^@ http://purl.uniprot.org/uniprot/Q8BH74 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleoporin Nup84/Nup107 family.|||Nucleus membrane|||Part of the nuclear pore complex (NPC) (By similarity). Forms part of the Nup160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and Nup96; this complex plays a role in RNA export and in tethering Nup98 and NUP153 to the nucleus (By similarity). Does not interact with TPR (By similarity). Interacts with ZNF106 (PubMed:28072389).|||Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. Required for the assembly of peripheral proteins into the NPC. May anchor NUP62 to the NPC. Involved in nephrogenesis.|||kinetochore|||nuclear pore complex http://togogenome.org/gene/10090:Fthl17c ^@ http://purl.uniprot.org/uniprot/A2AHC6 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Xkr8 ^@ http://purl.uniprot.org/uniprot/Q8C0T0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated upon caspase cleavage to generate the XK-related protein 8, processed form (By similarity). Does not act prior the onset of apoptosis (By similarity).|||Belongs to the XK family.|||Cell membrane|||Conditional knockout mice show defects in phosphatidylserine exposure following apoptosis, leading to defects in engulfment of apoptotic cells (PubMed:23845944, PubMed:29440417). Mice on the MRL background develop a lupus-like autoimmune disease caused by impaired clearance of apoptotic lymphocytes and aged neutrophils (PubMed:29440417). Male mice are infertile due to reduced sperm counts in their epididymides: defects are caused by inefficient clearance of apoptotic germ cells by Sertoli cells in testes (PubMed:31712393).|||Homodimer.|||Interacts with BSG and NPTN; which act as chaperones to localize XKR8 at the cell membrane.|||Phospholipid scramblase that promotes phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:25231987, PubMed:27503893, PubMed:29440417, PubMed:30718401). Phosphatidylserine is a specific marker only present at the surface of apoptotic cells and acts as a specific signal for engulfment (PubMed:23845944, PubMed:29440417, PubMed:30718401, PubMed:31712393). Required for the clearance of apoptotic cells, such as engulfment of apoptotic germ cells by Sertoli cells, clearance of senescent neutrophils or regulation of bipolar cell numbers in the retina (PubMed:30559640, PubMed:29440417, PubMed:31712393). Has no effect on calcium-induced exposure of phosphatidylserine (By similarity). Promotes myoblast differentiation and survival (PubMed:28881496).|||Phosphorylation at Thr-375 activates the phospholipid scramblase activity.|||Undergoes proteolytic processing by caspase-3 (CASP3), leading to its activation.|||Widely expressed with higher expression in testis (PubMed:23845944). Expressed in the bone marrow and mononuclear leukocytes in the blood; highly expressed in thymocytes and lymphocytes (PubMed:29440417). Expressed in the mature retina (PubMed:30559640).|||perinuclear region http://togogenome.org/gene/10090:Soga1 ^@ http://purl.uniprot.org/uniprot/A2ACV6 ^@ Similarity ^@ Belongs to the SOGA family. http://togogenome.org/gene/10090:Tulp1 ^@ http://purl.uniprot.org/uniprot/Q9Z273 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TUB family.|||Cell membrane|||Cytoplasm|||Homodimer (Probable). May interact with ABCF1, PSIP1, ZEB1 and HMGB2 (Potential). Interacts with F-actin (By similarity). Interacts with DNM1. Interacts with TUB. Interacts with TYRO3.|||Malformation of photoreceptor synapses, followed by photoreceptor degeneration.|||Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells. Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro) (By similarity). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages.|||Retina specific. Detected in the outer plexiform layer in photoreceptor cells (at protein level).|||Secreted|||Synapse http://togogenome.org/gene/10090:Crebl2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0D8|||http://purl.uniprot.org/uniprot/Q32M00 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. ATF subfamily.|||Interacts with CREB1; regulates CREB1 phosphorylation, stability and transcriptional activity.|||Nucleus|||Phosphorylated by AMPK.|||Probable regulator of CREB1 transcriptional activity which is involved in adipose cells differentiation. May also play a regulatory role in the cell cycle.|||Up-regulated during preadipocyte differentiation (at protein level).|||Widely expressed with higher expression in adipose tissue, skeletal muscle, and liver (at protein level). http://togogenome.org/gene/10090:Nfat5 ^@ http://purl.uniprot.org/uniprot/Q9WV30 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, expressed in brain and developing lens. At 12.5 dpc, the expression is extended to liver. By 17.5 dpc, expressed abundantly in brain, spinal cord, heart end liver and moderately in salivary gland, lung, kidney, gut and bladder (at protein level).|||Chromosome|||Cytoplasm|||Detected in white and brown adipose tissue, muscle, heart, liver and kidney. Expressed in lymphocytes (at protein level).|||Embryonic and perinatal lethality with incomplete penetrance. At 17.5 dpc, 50% of the expected Mendelian rate with only 3.4% of the expected number living past 21 days after birth. The few survivors to adulthood fail to thrive and their weight is half compared to the wild-type. At 3 weeks old, kidney hypoplasia and an altered medullary morphology are observed with an increased apoptosis in the kidney inner medulla. Under osmotic stress, the transcriptional regulation of osmoprotective genes is altered in the kidney medulla.|||Homodimer when bound to DNA, completely encircles its DNA target (By similarity). Interacts with CIDEC; this interaction is direct and retains NFAT5 in the cytoplasm (By similarity). Does not bind with Fos and Jun transcription factors. Interacts with DDX5 and DDX17; this interaction leads to DDX5/DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-mediated DDX5/DDX17-enhanced transactivation (By similarity).|||May have longer half-life and is more efficient in stimulation of transcription than isoform 3.|||Nucleus|||Phosphorylated at Thr-135 by CDK5 in response to osmotic stress; this phosphorylation mediates its rapid nuclear localization.|||Poly-ADP-ribosylated by PARP1 in response to DNA damage, promoting recruitment to sites of R-loop-associated DNA damage.|||The transcript encoding this isoform contains an alternative coding exon 4 which contains 2 stop codons and could target the transcript to nonsense-mediated mRNA decay after the pioneer round of translation, as suggested by decreased NFAT5 protein levels when the number of exon 4-containing transcripts increases. The insertion of exon 4 is stimulated in the presence of DDX5 and DDX17.|||Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes (PubMed:11934689, PubMed:14983020). Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (By similarity). Mediates the transcriptional response to hypertonicity (By similarity). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (By similarity). Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (By similarity).|||Up-regulated upon hypertonic conditions, this up-regulation in not observed in ES cells. http://togogenome.org/gene/10090:P4ha1 ^@ http://purl.uniprot.org/uniprot/E9Q7B0|||http://purl.uniprot.org/uniprot/Q3TTT2|||http://purl.uniprot.org/uniprot/Q3UF16|||http://purl.uniprot.org/uniprot/Q60715 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the P4HA family.|||Binds 1 Fe(2+) ion per subunit.|||Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.|||Endoplasmic reticulum lumen|||Expressed at least in brain, heart and lung.|||Heterotetramer of two alpha-1 chains and two beta chains (P4HB)(the beta chain is the multi-functional PDI), where P4HB plays the role of a structural subunit; this tetramer catalyzes the formation of 4-hydroxyproline in collagen.|||Inhibited by poly(L-proline). http://togogenome.org/gene/10090:Lime1 ^@ http://purl.uniprot.org/uniprot/Q9EQR5 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in spleen and lung. Present in primary B-cells and peripheral T-cells (at protein level).|||Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. In absence of TCR signaling, may be involved in CD4-mediated inhibition of T-cell activation. Couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilization or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules.|||Palmitoylation of Cys-28 and Cys-31 is required for raft targeting.|||Phosphorylated on tyrosines upon TCR activation and/or CD4 coreceptor stimulation, or upon BCR stimulation; which leads to the recruitment of SH2-containing proteins.|||Up-regulated in T-cells following TCR engagement.|||When phosphorylated in response to TCR stimulation and/or CD4 costimulation, interacts with LCK, CSK, FYN, PTPN11/SHP2, GRB2, PIK3R1 and GRAP2 (By similarity). When phosphorylated in response to BCR activation, interacts with LYN, PIK3R1, PLCG2 and GRB2. http://togogenome.org/gene/10090:Tnik ^@ http://purl.uniprot.org/uniprot/P83510 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Autophosphorylation is activated by RAP2A and induces association to the cytoskeletal fraction.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Interacts (via the CNH domain) with RAP2A (GTP-bound form preferentially); the interaction is direct and required for the activation of TNIK by RAP2A. Interacts with NEDD4; recruits RAP2A to NEDD4. Interacts with TRAF2 and NCK. Interacts with TCF7L2/TCF4 and CTNNB1; the interaction is direct. Interacts with TANC1.|||Nucleus|||Probable cloning artifact.|||Recycling endosome|||Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Ext2 ^@ http://purl.uniprot.org/uniprot/P70428|||http://purl.uniprot.org/uniprot/Q3UDB5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 47 family.|||Endoplasmic reticulum membrane|||Expressed in early stages of embryonic development.|||Expressed in heart, brain, spleen, lung, liver, skeletal muscle and testis. Heart shows a high expression.|||Forms a homo/heterooligomeric complex with EXT1. Interacts with GALNT5. Interacts with NDST1.|||Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a tumor suppressor. Required for the exosomal release of SDCBP, CD63 and syndecan.|||Golgi apparatus membrane|||Membrane|||cis-Golgi network membrane http://togogenome.org/gene/10090:Cdkn2c ^@ http://purl.uniprot.org/uniprot/Q60772 ^@ Function|||Similarity|||Subunit ^@ Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.|||Heterodimer of p18 with CDK6.|||Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB. http://togogenome.org/gene/10090:Larp4b ^@ http://purl.uniprot.org/uniprot/Q6A0A2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with PABPC1. Interacts with RACK1. Associates with polysomes via the 40S ribosomal subunit.|||Stimulates mRNA translation.|||cytosol http://togogenome.org/gene/10090:Pdcl3 ^@ http://purl.uniprot.org/uniprot/Q8BVF2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a chaperone for the angiogenic VEGF receptor KDR/VEGFR2, increasing its abundance by inhibiting its ubiquitination and degradation (PubMed:26059764). Inhibits the folding activity of the chaperonin-containing T-complex (CCT) which leads to inhibition of cytoskeletal actin folding (By similarity). Acts as a chaperone during heat shock alongside HSP90 and HSP40/70 chaperone complexes (By similarity). Modulates the activation of caspases during apoptosis (By similarity).|||Belongs to the phosducin family.|||By hypoxia and heat shock.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in blood vessels (at protein level).|||Interacts (via thioredoxin fold region) with KDR/VEGFR2 (via juxtamembrane domain) (By similarity). Forms ternary complexes with the chaperonin CCT complex and actin substrate, leading to inhibition of actin folding (By similarity). Interacts with XIAP (via BIR 3 and RING domain) (By similarity). Interacts with HSP90AA1 and HSP90AB1 (PubMed:27496612).|||N-terminal methionine acetylation destabilizes the protein.|||perinuclear region http://togogenome.org/gene/10090:Dhrs3 ^@ http://purl.uniprot.org/uniprot/G5E8W9|||http://purl.uniprot.org/uniprot/O88876 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the reduction of all-trans-retinal to all-trans-retinol in the presence of NADPH.|||In the embryo, expressed in developing osteogenic and chondrogenic tissues of vertebra, rib, tooth and limb bud.|||Membrane http://togogenome.org/gene/10090:Mef2b ^@ http://purl.uniprot.org/uniprot/Q80VR4 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:H4c9 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Ndc1 ^@ http://purl.uniprot.org/uniprot/Q8VCB1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NDC1 family.|||Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane (By similarity).|||Interacts with the NUP35/NUP53.|||Nucleus membrane|||Phosphorylated.|||nuclear pore complex http://togogenome.org/gene/10090:Arhgap15 ^@ http://purl.uniprot.org/uniprot/Q811M1 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Cytoplasm|||GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has activity toward RAC1. Overexpression results in an increase in actin stress fibers and cell contraction (By similarity).|||Membrane|||The PH domain is required for localization to the membrane. http://togogenome.org/gene/10090:Or14c41 ^@ http://purl.uniprot.org/uniprot/Q7TS08 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnj1 ^@ http://purl.uniprot.org/uniprot/G3UWE7|||http://purl.uniprot.org/uniprot/O88335 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ1 subfamily.|||Cell membrane|||In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium (By similarity).|||Inhibited by WNK3.|||Interacts with SGK1 and SLC9A3R2/NHERF2.|||Membrane|||Phosphorylation at Ser-25 by SGK1 is necessary for its expression at the cell membrane. http://togogenome.org/gene/10090:Dqx1 ^@ http://purl.uniprot.org/uniprot/Q924H9 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Tgoln1 ^@ http://purl.uniprot.org/uniprot/Q62313 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Also found in strains BALB/c, C57BL/6 and DBA/2.|||Cell membrane|||May be involved in regulating membrane traffic to and from trans-Golgi network.|||Widely expressed.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Tmod1 ^@ http://purl.uniprot.org/uniprot/P49813 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tropomodulin family.|||Binds to the N-terminus of tropomyosin and to actin.|||Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity).|||Highly expressed in the erythrocyte, heart and skeletal muscle.|||cytoskeleton http://togogenome.org/gene/10090:Tmem98 ^@ http://purl.uniprot.org/uniprot/Q91X86 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM98 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in differentiated oligodendrocytes in early postanatal central nervous system tissues (PubMed:30249802). Expressed by CD4(+) T cells, the expression increases upon activation (at protein level) (PubMed:25946230).|||Functions as a negative regulator of MYRF in oligodendrocyte differentiation and myelination. Interacts with the C-terminal of MYRF inhibiting MYRF self-cleavage and N-fragment nuclear translocation (PubMed:25946230). The secreted form promotes differentiation of T helper 1 cells (Th1) (PubMed:25946230).|||In the spinal cord region, expression is initially detected in the ventral white matter at 18.5 dpc, up-regulates rapidly afterward, and peaks at early postnatal stages from P4 to P7. At P15, expression starts to be detected in the gray matter of spinal cord but gradually disappears thereafter. Also observed in corpus callosum and the white matter of cerebellum at P15 stages.|||Interacts (via N-terminal region) with MYRF; the interaction inhibits MYRF self-cleavage.|||Secreted|||extracellular exosome http://togogenome.org/gene/10090:Cldn13 ^@ http://purl.uniprot.org/uniprot/Q547B2|||http://purl.uniprot.org/uniprot/Q9Z0S4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Rpp40 ^@ http://purl.uniprot.org/uniprot/Q8R1F9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.|||nucleolus http://togogenome.org/gene/10090:Apba2 ^@ http://purl.uniprot.org/uniprot/P98084 ^@ Caution|||Domain|||Function|||Subunit|||Tissue Specificity ^@ Composed of an N-terminal domain that binds STXBP1, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane.|||Part of a multimeric complex containing STXBP1 and syntaxin-1. Binds to the cytoplasmic domain of amyloid-beta protein, and to the nuclear factor NF-kappa-B/p65 via its PDZ domain. Interacts with the N-terminal domain of NECAB3 (By similarity).|||Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta.|||Specifically expressed in neurons, predominantly of the cerebellum, hippocampus, and spinal cord. Lesser extent in neurons of the cerebral cortex and anterior thalmic nuclei.|||Was originally thought to be the ortholog of human X11 (APBA1). http://togogenome.org/gene/10090:Crebbp ^@ http://purl.uniprot.org/uniprot/A0A0U1RQB6|||http://purl.uniprot.org/uniprot/F8VPR5 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Or5m10 ^@ http://purl.uniprot.org/uniprot/A2ASU6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hspa9 ^@ http://purl.uniprot.org/uniprot/P38647 ^@ Function|||Induction|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis (PubMed:26702583). Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (By similarity). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823). May play a role in the control of cell proliferation and cellular aging (PubMed:8454632).|||Found in all the cell types examined.|||Interacts strongly with the intermediate form of FXN and weakly with its mature form. Interacts with HSCB. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1, MTX2 and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. Interacts with DNLZ, the interaction is required to prevent self-aggregation. Interacts with TESPA1. Interacts with PDPN. Interacts with NFU1, NFS1 and ISCU.|||Mitochondrion|||Not induced by heat shock, instead protein level is decreased.|||Two forms of the protein have been found, MOT-1, found in mortal cells and MOT-2, found in immortal cells. The sequence of MOT-2 is shown here.|||nucleolus http://togogenome.org/gene/10090:Tfap2a ^@ http://purl.uniprot.org/uniprot/A0A0R4J1E6|||http://purl.uniprot.org/uniprot/A0A286YCU0|||http://purl.uniprot.org/uniprot/A0A286YD43|||http://purl.uniprot.org/uniprot/P34056|||http://purl.uniprot.org/uniprot/Q3UL09|||http://purl.uniprot.org/uniprot/Q8BPN4 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ All isoforms are induced during retinoic acid-mediated differentiation and by cAMP stimulation of primary astrocytes. Isoform 3 is most strongly induced in the former case, isoform 1 in the latter case.|||Belongs to the AP-2 family.|||Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with WWOX. Interacts with UBE2I. Interacts with RALBP1 in a complex also containing EPN1 and NUMB during interphase and mitosis (By similarity). Interacts with CITED4. Interacts with KCTD1; this interaction represses transcription activation. Interacts (via C-terminus) with CITED2 (via C-terminus); the interaction stimulates TFAP2A-transcriptional activation. Interacts (via N-terminus) with EP300 (via N-terminus); the interaction requires CITED2 (By similarity). Interacts with KCTD15; this interaction inhibits TFAP2A transcriptional activation (By similarity).|||Expressed in the embryonic heart. Expressed from embryo day 9.5 to birth. At day 12.5, expressed in the midbrain, hindbrain, spinal cord, sensory ganglia, epidermis, nephric system and limbs. At mid-embryogenesis, isoform 3 is the most abundant form in the nervous system and total embryo, but the least abundant form in the epidermis. In adults, AP-2A is expressed in the eye, skin, kidney, prostate, thymus, skeletal muscle and very weakly, in the brain. Highest expression found in skin and eye.|||Nucleus|||Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region.|||Sumoylated on Lys-10; which inhibits transcriptional activity.|||The PPxY motif mediates interaction with WWOX. http://togogenome.org/gene/10090:Clmn ^@ http://purl.uniprot.org/uniprot/Q8C5W0 ^@ Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis. Expressed during testis maturation process and in maturing spermatids. In brain, it is expressed in neurons of the hippocampus, cerebral cortex, and thalamus, Purkinje cells, and also in the choroid plexus and ependymal cells. Expressed predominantly in dendrites and cell bodies of the neurons, but not in axons. The level of expression increases during the period of maturation of the mouse brain after birth.|||Lacks the transmembrane domain.|||Membrane http://togogenome.org/gene/10090:Vav1 ^@ http://purl.uniprot.org/uniprot/P27870 ^@ Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.|||Interacts with SHB (By similarity). Interacts with APS, DOCK2, GRB2, GRB3, DOCK2, SLA, TEC and ZNF655/VIK. Interacts with SIAH2; without leading to its degradation. Associates with BLNK, PLCG1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with CBLB; which inhibits tyrosine phosphorylation and down-regulates activity (PubMed:10646609, PubMed:10646608). May interact with CCPG1 (PubMed:17000758). Interacts with CLNK (PubMed:11463797). Interacts with THEMIS2 (PubMed:20644716). Interacts with NEK3 and this interaction is prolactin-dependent. Interacts with ITK. Interacts with PTK2B/PYK2 (By similarity). Interacts with HCK. Interacts with PTK2B/PYK2. Interacts (via SH2 domain) with SYK (By similarity). Interacts with ANKRD54 (PubMed:19064729). Interacts with CD6 (PubMed:24584089). Interacts with isoform 2 of CRACR2A (By similarity).|||Phosphorylated by FYN (By similarity). Phosphorylated on tyrosine residues by HCK in response to IFNG and bacterial lipopolysaccharide (LPS).|||The DH domain is involved in interaction with CCPG1.|||Widely expressed in hematopoietic cells but not in other cell types. Found in the spleen and lung. http://togogenome.org/gene/10090:Tmcc3 ^@ http://purl.uniprot.org/uniprot/Q8R310 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 12.5 dpc, weak expression in the developing lung and hindbrain, high expression in the tongue mesenchyme (PubMed:27697108). At 14.5 dpc, expressed in the trigeminal ganglion, oral epithelium and hindbrain (PubMed:27697108). Also detected in lung, kidney and somites (PubMed:27697108).|||Belongs to the TEX28 family.|||Endoplasmic reticulum membrane|||May form homodimers and heterodimers with TMCC2 or TMCC3 via the coiled-coil domains. Interacts with ribosomal proteins RPL4 and RPS6. http://togogenome.org/gene/10090:Mkln1 ^@ http://purl.uniprot.org/uniprot/O89050 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (By similarity). Required for internalization of the GABA receptor GABRA1 from the cell membrane via endosomes and subsequent GABRA1 degradation (PubMed:21482357). Acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component THBS1 (PubMed:9724633, PubMed:18710924).|||Cytoplasm|||Detected in brain, especially in hippocampus and cerebellum (at protein level).|||Homodimer; may form higher oligomers (By similarity). Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles (By similarity). Interacts with RANBP9 (PubMed:18710924). Part of a complex consisting of RANBP9, MKLN1 and GID8 (By similarity). Interacts with GABRA1 (PubMed:21482357). Interacts with the C-terminal tail of PTGER3 (By similarity).|||No visible phenotype. Hippocampus slices from mutant mice show minor differences in the amplitude of miniature inhibitory postsynaptic currents, and somewhat slower decay times.|||Postsynapse|||Synapse|||The LisH domain contains a nuclear targeting signal (PubMed:18710924). The LisH domain mediates head to tail dimerization (By similarity).|||cell cortex|||cytosol|||nucleoplasm|||ruffle http://togogenome.org/gene/10090:Chmp3 ^@ http://purl.uniprot.org/uniprot/Q9CQ10 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF7 family.|||Endosome|||Expressed in lung, testis, heart, spleen, skeletal muscle, kidney, liver and brain.|||Late endosome membrane|||Membrane|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Selectively binds to phosphatidylinositol 3,5-bisphosphate PtdIns(3,5)P2 and PtdIns(3,4)P2 in preference to other phosphoinositides tested. Involved in late stages of cytokinesis. Plays a role in endosomal sorting/trafficking of EGF receptor (By similarity).|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Forms a metastable monomer in solution; its core structure (without part of the putative autoinhibitory C-terminal acidic region) oligomerizes into a flat lattice via two different dimerization interfaces. In vitro, heteromerizes with CHMP2A (but not CHMP4) to form helical tubular structures that expose membrane-interacting sites on the outside whereas VPS4B can associate on the inside of the tubule. May interact with IGFBP7; the relevance of such interaction however remains unclear. Interacts with CHMP2A. Interacts with CHMP4A; the interaction requires the release of CHMP4A autoinhibition. Interacts with VPS4A. Interacts with STAMBP; the interaction appears to relieve the autoinhibition of CHMP3 (By similarity). Interacts with VTA1 (By similarity).|||The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components.|||cytosol http://togogenome.org/gene/10090:Mtf2 ^@ http://purl.uniprot.org/uniprot/Q02395 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:21367819, PubMed:22438827). Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin (By similarity).|||Belongs to the Polycomblike family.|||Contaminating sequence. Potential poly-A sequence.|||Mice survive to birth; however, most of them die before weaning. Axial skeletal alterations that are characteristic of posterior transformations are observed: ectopic ribs that associate with the seventh cervical vertebra (C7) are frequently observed. Consistent with this malformation, sternums are shifted anteriorly. The odontoid process, which is normally a characteristic of the second cervical vertebra (C2), is frequently associated with the first cervical vertebra (C1).|||Nucleus|||Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity (PubMed:20144788, PubMed:21367819, PubMed:21059868, PubMed:23104054, PubMed:22438827). Regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation (PubMed:20144788). Promotes recruitment of the PRC2 complex to the inactive X chromosome in differentiating XX ES cells and PRC2 recruitment to target genes in undifferentiated ES cells (PubMed:21367819). Required to repress Hox genes by enhancing H3K27me3 methylation of the PRC2 complex (PubMed:21059868). In some conditions may act as an inhibitor of PRC2 activity: able to activate the CDKN2A gene and promote cellular senescence by suppressing the catalytic activity of the PRC2 complex locally (PubMed:21059868). Binds to the metal-regulating-element (MRE) of MT1A gene promoter (PubMed:7772254).|||The Tudor domain recognizes and binds H3K36me3. http://togogenome.org/gene/10090:Zfp82 ^@ http://purl.uniprot.org/uniprot/Q6P9Y7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Nfkbie ^@ http://purl.uniprot.org/uniprot/O54910 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NF-kappa-B inhibitor family.|||Cytoplasm|||Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. Inhibits DNA-binding of NF-kappa-B p50-p65 and p50-c-Rel complexes (By similarity).|||Interacts with RELA, REL, NFKB1 nuclear factor NF-kappa-B p50 subunit and NFKB2 nuclear factor NF-kappa-B p52 subunit.|||Serine phosphorylated; followed by proteasome-dependent degradation. http://togogenome.org/gene/10090:Wnt8b ^@ http://purl.uniprot.org/uniprot/Q3TER4|||http://purl.uniprot.org/uniprot/Q8BQD1|||http://purl.uniprot.org/uniprot/Q9WUD6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Wnt family.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Ligand for members of the frizzled family of seven transmembrane receptors. May play an important role in the development and differentiation of certain forebrain structures, notably the hippocampus.|||Palmitoleoylation is required for efficient binding to frizzled receptors (By similarity). Depalmitoleoylation leads to Wnt signaling pathway inhibition (By similarity).|||Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT8B.|||extracellular matrix http://togogenome.org/gene/10090:Slk ^@ http://purl.uniprot.org/uniprot/O54988 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Mediates apoptosis and actin stress fiber dissolution.|||Proteolytically cleaved by caspase-3.|||Ubiquitously expressed from day 7 to 17 dpc.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Dlx5 ^@ http://purl.uniprot.org/uniprot/P70396|||http://purl.uniprot.org/uniprot/Q3TYA7 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the distal-less homeobox family.|||Expressed in osteoblasts and chondrocytes.|||Expressed in the otic vesicle, mandibular arch, branchial arches 2 and 3, in proximal anterior mesodermal domain in the limb, immature and proliferating chondroblasts at 14.5 dpc.|||Interacts with XRCC6 (Ku70).|||Nucleus|||Phosphorylated. Phosphorylation of Ser-34 and Ser-217 by MAPK14 enhances its transcriptional activity. Phosphorylation by CaMK2 increases its protein stability.|||Transcriptional factor involved in bone development. Acts as an immediate early BMP-responsive transcriptional activator essential for osteoblast differentiation. Stimulates ALPL promoter activity in a RUNX2-independent manner during osteoblast differentiation. Stimulates SP7 promoter activity during osteoblast differentiation. Promotes cell proliferation by up-regulating MYC promoter activity. Involved as a positive regulator of both chondrogenesis and chondrocyte hypertrophy in the endochondral skeleton. Binds to the homeodomain-response element of the ALPL and SP7 promoter. Binds to the MYC promoter. Requires the 5'-TAATTA-3' consensus sequence for DNA-binding.|||Up-regulated by BMP2. http://togogenome.org/gene/10090:Snx2 ^@ http://purl.uniprot.org/uniprot/Q9CWK8 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Early endosome membrane|||Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity. Required for retrograde endosome-to-TGN transport of TGN38. Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (By similarity).|||No visible phenotype. Mice are born at the expected Mendelian ratio and are fertile. Mice lacking both Snx1 and Snx2 die during embryonic development, around 9.5 and 11.5 dpc.|||Predominantly forms heterodimers with BAR domain-containing sorting nexins SNX5, SNX6 and SNX32; can self-associate to form homodimers. The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. Interacts with SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35, FNBP1, KALRN, RHOG (GDP-bound form) (By similarity).|||The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of a N-terminal amphipathic helix (AH) in the membrane (By similarity).|||lamellipodium http://togogenome.org/gene/10090:Dnaaf10 ^@ http://purl.uniprot.org/uniprot/Q8BGF3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (By similarity). Interacts with PIH1D1; the interaction associates DNAAF10 with the R2TP complex (By similarity). Interacts with several dynein axonemal assembly factors (By similarity).|||Dynein axonemal particle|||Key assembly factor specifically required for the stability of axonemal dynein heavy chains in cytoplasm. http://togogenome.org/gene/10090:Herpud1 ^@ http://purl.uniprot.org/uniprot/Q9JJK5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Binds to ubiquilins and this interaction is required for efficient degradation of CD3D via the ERAD pathway.|||Endoplasmic reticulum membrane|||Interacts with PSEN1 and PSEN2 (By similarity). Interacts with UBXN6 (By similarity). Interacts with UBQLN1, UBQLN2 and UBQLN4 (By similarity). Component of the HRD1 complex, which comprises at least SYNV1/HRD1, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1. FAM8A1 binding to SYNV1 may promote recruitment of HERPUD1 to the HRD1 complex (By similarity). http://togogenome.org/gene/10090:Pde6d ^@ http://purl.uniprot.org/uniprot/O55057|||http://purl.uniprot.org/uniprot/Q3TDQ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PDE6D/unc-119 family.|||Cytoplasmic vesicle membrane|||Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains (PDE6A and PDE6B) and two inhibitory chains (gamma); has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane (By similarity). Interacts with prenylated GRK1 and GRK7 (By similarity). Interacts with prenylated INPP5E (By similarity). Interacts with prenylated Ras family members, including HRAS, KRAS, NRAS, RAP2A, RAP2C and RHEB (PubMed:22179043). Interacts with RAB13 (prenylated form); dissociates RAB13 from membranes (By similarity). Interacts with RPGR (PubMed:9990021). Interacts with ARL2 (PubMed:15979089). Interacts with ARL3; the interaction occurs specifically with the GTP-bound form of ARL3 (PubMed:15979089). Interaction with ARL2 and ARL3 promotes release of farnesylated cargo proteins (By similarity).|||Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains and two inhibitory chains; has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane.|||Promotes the release of prenylated target proteins from cellular membranes (PubMed:22179043). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22179043). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (By similarity). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (PubMed:22179043). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.|||Promotes the release of prenylated target proteins from cellular membranes. Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location. Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E. Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.|||cilium basal body|||cytosol http://togogenome.org/gene/10090:Cnnm1 ^@ http://purl.uniprot.org/uniprot/Q0GA42 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ACDP family.|||Cell membrane|||Predominantly expressed in brain and testis, and, at lower levels, in kidney. In the brain, expressed in hippocampal neurons (at protein level).|||Probable metal transporter.|||Shares weak sequence similarity with the cyclin family, explaining its name. However, it has no cyclin-like function in vivo. http://togogenome.org/gene/10090:Cgnl1 ^@ http://purl.uniprot.org/uniprot/Q6AW69 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cingulin family.|||Homodimer or oligomer (Probable). Interacts with CD2AP and SH3BP1; probably part of a complex at cell junctions (By similarity).|||May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons.|||Probable cloning artifact.|||The head region is responsible for both junction and actin filament-based distribution.|||Widely expressed. Highly expressed in the kidney and lung.|||tight junction http://togogenome.org/gene/10090:H2-M3 ^@ http://purl.uniprot.org/uniprot/Q31093 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Golga2 ^@ http://purl.uniprot.org/uniprot/Q921M4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GOLGA2 family.|||Cleaved by caspases at the onset of apoptosis.|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Extended rod-like protein with long coiled-coil domains.|||Homodimer, may assemble into homohexamers (By similarity). Homotetramer; forms a parallel homotetramer with a flexible rod-like structure that can give rise to I- and Y-shaped conformations. Interacts with GORASP1/GRASP65. The homooligomer forms a complex with GORASP1 with a 1:1 stoichiometry (By similarity). Interacts with RAB1B that has been activated by GTP-binding. Interacts with p115/USO1; interaction with p115/USO1 inhibits interaction with STX5 and/or RAB1B. Interacts with STX5 (By similarity). Interacts with ZFPL1 (By similarity). Interacts with AKAP450/AKAP9; leading to recruit AKAP450/AKAP9 to the cis-Golgi (By similarity).|||Methylation by PRMT5 is required for Golgi ribbon formation.|||Mice are born at the expected Mendelian rate and have normal weight at birth. However, they display strongly decreased growth during the following weeks and die between 15 and 35 days after birth. Mice display ataxia and motor coordination defects that worsen with increasing age. Mice with a neuron-specific gene disruption display normal overall brain architecture, but the size of the cerebellum is strongly reduced in adults. After the third week after birth, a progressive loss of Purkinje cell is observed, leading to cerebellar atrophy. Purkinje cells from mutant mice appear normal at 9 days after birth, but display a strong decrease of the size and arborization of dendrites, associated with impaired dendritic protein transport. Other neurons in the molecular or granule layer of the cerebellum are not affected. Mice with a neuron-specific gene disruption display decreased growth, but have a normal lifespan and have only mild motor coordination defects at three weeks after birth, but defects are obvious at 8 weeks after birth.|||Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane (PubMed:28028212). Required for normal protein transport from the endoplasmic reticulum to the Golgi apparatus and the cell membrane (PubMed:28028212). Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis. Also plays a key role in spindle pole assembly and centrosome organization (By similarity). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (By similarity). Regulates the meiotic spindle pole assembly, probably via the same mechanism (PubMed:21552007). Also regulates the centrosome organization (By similarity). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (By similarity).|||Phosphorylated at Ser-37 by CDK1 at the onset of mitosis, inhibiting the interaction with p115/USO1 and triggering Golgi disassembly. A report however suggests that Golgi disassembly is independent of phosphorylation at Ser-37. Phosphorylated at Ser-37 in prophase as the Golgi complex starts to break down, and remains phosphorylated during further breakdown and partitioning of the Golgi fragments in metaphase and anaphase. In telophase, GM130 is dephosphorylated by PP2A as the Golgi fragments start to reassemble.|||The nuclear localization signal (cNLS) mediates interaction with importin-alpha, recruiting importin-alpha to the Golgi membrane and liberating TPX2.|||Widely expressed. Detected in brain, kidney, lung, liver, spleen, heart, skeletal muscle, thymus and pancreas (PubMed:28028212, PubMed:26742501). Detected in spermatocytes (PubMed:28617811). Present in oocytes during all oocyte meiotic maturation (at protein level).|||cis-Golgi network membrane|||spindle pole http://togogenome.org/gene/10090:Fibp ^@ http://purl.uniprot.org/uniprot/Q9JI19 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds to internalized FGF1; this interaction is increased in the presence of CSNKB, suggesting a possible cooperative interaction between CSNKB and FIBP in binding to FGF1.|||Endomembrane system|||Expressed throughout the development in embryo at 10.5 dpc. Expressed in the central nervous system at 12.5 dpc. Expressed in the ventral part of caudal diencephalon at 12.5 dpc. Expressed in the dorsal root ganglia at 12.5 dpc. Expressed in the kidney and lung at 12.5 dpc. Expressed in the dorsal and ventral midbrain at 18.5 dpc. Expressed uniformely in the cortex at 18.5 dpc.|||May be involved in mitogenic function of FGF1 (By similarity). May mediate with IER2 FGF-signaling in the establishment of laterality in the embryo (By similarity).|||Nucleus http://togogenome.org/gene/10090:Chac1 ^@ http://purl.uniprot.org/uniprot/Q8R3J5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.|||Catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides. Glutathione depletion is an important factor for apoptosis initiation and execution. Acts as a pro-apoptotic component of the unfolded protein response pathway by mediating the pro-apoptotic effects of the ATF4-ATF3-DDIT3/CHOP cascade (By similarity). Negative regulator of Notch signaling pathway involved in embryonic neurogenesis: acts by inhibiting Notch cleavage by furin, maintaining Notch in an immature inactive form, thereby promoting neurogenesis in embryos (PubMed:22445366).|||Interacts with NOTCH1 (via extracellular region).|||Widely expressed, with high expression in forebrain and anterior spinal cord. Expressed at intermediate level in the dorsal aorta and heart. Present throughout adult brain (at protein level).|||cytosol|||trans-Golgi network http://togogenome.org/gene/10090:Mrpl33 ^@ http://purl.uniprot.org/uniprot/Q9CQP0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL33 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Dcstamp ^@ http://purl.uniprot.org/uniprot/A0A2I3BPX1|||http://purl.uniprot.org/uniprot/Q7TNJ0 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Endosome|||Expressed in macrophages and bone marrow dendritic cells (BM-DC). Weakly expressed in the spleen and lymph node. Highly expressed in multi-nuclear osteoclasts compared to mono-nuclear macrophages. Expressed in foreign body giant cells (FBGCs). Isoform 1 and isoform 2 are expressed in osteoclasts.|||Glycosylated.|||Interacts with CREB3 (By similarity). Monomer. Homodimer. Isoform 1 interacts (via the C-terminus cytoplasmic tail) with OS9 isoform 1 (via the C-terminus tail); the interaction induces DCSTAMP redistribution to the endoplasmic reticulum-Golgi intermediate compartment. Isoform 1 interacts (via the C-terminus cytoplasmic tail) with OS9 isoform 2 (via the C-terminus tail).|||Membrane|||Mice show a lack of osteoclast and foreign body giant cells multi-nuclear formation and a bone-resorbing efficiency reduction. Mice show increased bone mass. Older (>12 months) mice suffered from multisystemic inflammations in the kidney, lung and salivary gland. Mice show autoimmune symptoms, like dendritic cells (DC) with increased phagocytotic activity and antigen presentation.|||Probable cell surface receptor that plays several roles in cellular fusion, cell differentiation, bone and immune homeostasis. Plays a role in TNFSF11-mediated osteoclastogenesis. Cooperates with OCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign body giant cells (FBGCs). Participates in osteoclast bone resorption. Involved in inducing the expression of tartrate-resistant acid phosphatase in osteoclast precursors. Plays a role in haematopoietic stem cell differentiation of bone marrow cells toward the myeloid lineage. Inhibits the development of neutrophilic granulocytes. Plays also a role in the regulation of dendritic cell (DC) antigen presentation activity by controlling phagocytic activity. Involved in the maintenance of immune self-tolerance and avoidance of autoimmune reactions.|||Several domains are necessary for interacting with OS9. The region in the cytoplasmic tail that is necessary for interaction with OS9, is also required for its transport.|||Up-regulated by IL4/interleukin-4, macrophage colony-stimulating factor (M-CSF), receptor activator of NF-KB ligand (RANKL), lipopolysaccharide (LPS) and toll-like receptor (TLR). Up-regulated by TNFSF11-induced osteoclast differentiation in combination with TNF-alpha. Down-regulated upon dendritic cell (DC) maturation. http://togogenome.org/gene/10090:Npas4 ^@ http://purl.uniprot.org/uniprot/Q8BGD7 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein (PubMed:14701734, PubMed:15363889, PubMed:19284974). Heterodimer; forms a heterodimer with ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:15363889, PubMed:19284974).|||Induced upon calcium influx (PubMed:26663079). Expression is regulated by neuronal activity (at protein level) (PubMed:18815592, PubMed:22194569, PubMed:24201284, PubMed:24855953). Induced in CA3 region of the hippocampus after contextual learning (PubMed:22194569). Induced following sensory input in newborn olfactory bulb interneurons (PubMed:25088421). Induced in the medial prefrontal cortex cells of the brain following experiences with positive valence (PubMed:27238022). Induced in pancreatic beta cells in response to calcium influx (PubMed:26663079). Down-regulated by REST (PubMed:24291638). Transcripts are regulated by a subset of miRNAs, such as miR-203, miR-224 and miR-744, that bind to its 3'-UTR region and down-regulate its expression (PubMed:24291638, PubMed:27189618).|||Mainly expressed in brain (PubMed:14701734, PubMed:15363889). Expressed in the limbic system and olfactory bulb (PubMed:15363889, PubMed:25088421). Specifically expressed in CA1 and CA3 region of the hippocampus after contextual learning (at protein level) (PubMed:22194569, PubMed:23029555). Also expressed in pancreatic beta cells (PubMed:26663079).|||Mice appear anxious and hyperactive, are prone to seizures and have a shortened lifespan compared with their wild-type littermates (PubMed:18815592, PubMed:19001414, PubMed:23029555, PubMed:25549857). Mice show learning and memory deficits: while having intact memories 5 minutes after training, memory is significantly reduced one hour or 24 hours following training, suggesting that both short-term memory and long-term memory are impaired (PubMed:22194569). Mice show social and cognitive defects: they are hyperactive in a novel environment, spend less time exploring, show higher social dominance than their wild-type littermates and display pre-pulse inhibition, working memory, long-term memory and cognitive flexibility deficits (PubMed:23029555). When exposed to an enriched environment, a significantly less frequent and slightly smaller amplitude inhibitory postsynaptic current is observed (PubMed:24201284). Mice show a reduction in the dendritic spine density in olfactory bulb granule cells, leading to impaired odor discrimination learning (PubMed:25088421). Mice also show increased vulnerability to juvenile stress: mice exposed to chronic mild stress during adolescence, but not during adulthood, develop prefrontal cortex-dependent cognitive deficits in adulthood (PubMed:25911220).|||Nucleus|||Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hippocampus (PubMed:18815592, PubMed:22194569, PubMed:23029555, PubMed:24201284, PubMed:24855953). Plays a key role in the structural and functional plasticity of neurons (PubMed:23172225). Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (PubMed:24201284, PubMed:24855953). In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (PubMed:18815592, PubMed:22194569, PubMed:24201284). In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (PubMed:24855953). The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (PubMed:18815592, PubMed:22194569, PubMed:23029555, PubMed:24201284, PubMed:27238022). Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (PubMed:25088421). Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734, PubMed:15363889, PubMed:19284974). Can activate the CME (CNS midline enhancer) element (PubMed:14701734, PubMed:15363889).|||Ubiquitinated, leading to degradation by the proteosome. http://togogenome.org/gene/10090:Rsrc1 ^@ http://purl.uniprot.org/uniprot/Q9DBU6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via Arg/Ser-rich domain) with LUC7L3, RBM39 and RSF1.|||Nucleus|||Nucleus speckle|||Phosphorylated.|||Plays a role in pre-mRNA splicing. Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3' splice site during the second step of splicing (By similarity). http://togogenome.org/gene/10090:Acd ^@ http://purl.uniprot.org/uniprot/B2RS36|||http://purl.uniprot.org/uniprot/Q5EE38 ^@ Developmental Stage|||Disease Annotation|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adrenocortical dysplasia mouse was initially reported as a model of human congenital adrenal hypoplasia (AHC).|||Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Forms heterodimers with POT1. Identified in a complex with POT1 and single-stranded telomeric DNA. Interacts with STN1 and TINF2.|||Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by recruiting telomerase to telomeres and increasing its processivity (By similarity). May play a role in organogenesis (PubMed:15537664).|||Defects in Acd are the cause of adrenocortical dysplasia (ACD). ACD is a spontaneous autosomal recessive mouse mutant resulting from spontaneous splicing mutation of acd. ACD mice are characterized by developmental defects in organs derived from the urogenital ridge, reduced survival, poor growth, skin hyperpigmentation and adrenal insufficiency. Forty percent of the mutants died within 24 hours. Analysis of 14.5 dpc to 17.5 dpc embryos revealed reduced formation of caudal structure as well as limb defects.|||Expressed from 7 dpc to 18 dpc throughout development.|||Nucleus|||Ubiquitous.|||telomere http://togogenome.org/gene/10090:Fcrl1 ^@ http://purl.uniprot.org/uniprot/Q8R4Y0 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||May function as an activating coreceptor in B-cells. May function in B-cells activation and differentiation (By similarity).|||Phosphorylated on tyrosines upon activation.|||Widely expressed. Expressed in B-cells at the various stages of differentiation. http://togogenome.org/gene/10090:Or8k53 ^@ http://purl.uniprot.org/uniprot/A2AVX9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aldh3a1 ^@ http://purl.uniprot.org/uniprot/P47739|||http://purl.uniprot.org/uniprot/Q3UNF5 ^@ Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde (Probable). They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (Probable). Oxidizes medium and long chain aldehydes into non-toxic fatty acids (PubMed:25286108). Preferentially oxidizes aromatic aldehyde substrates (PubMed:11784860). Comprises about 50 percent of corneal epithelial soluble proteins (PubMed:11784860). May play a role in preventing corneal damage caused by ultraviolet light (PubMed:10376761).|||Belongs to the aldehyde dehydrogenase family.|||Constitutively expressed in cornea, stomach, skin, bladder and lungs. Lowest expression levels in lungs and bladder.|||Cytoplasm|||Homodimer.|||There are two alleles, Ald3a1a and Ald3a1c. Ald3a1c codes for a low activity enzyme and is associated with extensive corneal clouding after exposure to ultraviolet light. Ald3a1a encodes the high activity enzyme. http://togogenome.org/gene/10090:Igfbpl1 ^@ http://purl.uniprot.org/uniprot/Q80W15 ^@ Function|||Subcellular Location Annotation ^@ IGF-binding proteins prolong the half-life of IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs in cell culture. They alter the interaction of IGFs with their cell surface receptors (By similarity).|||Secreted http://togogenome.org/gene/10090:Mpo ^@ http://purl.uniprot.org/uniprot/P11247 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxidase family. XPO subfamily.|||Binds 1 Ca(2+) ion per monomer.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per monomer.|||Homodimer; disulfide-linked. Each monomer consists of a light and a heavy chain (By similarity).|||Lysosome|||Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity (PubMed:11593004). Mediates the proteolytic cleavage of alpha-1-microglobulin to form t-alpha-1-microglobulin, which potently inhibits oxidation of low density lipoprotein particles and limits vascular damage (By similarity). http://togogenome.org/gene/10090:Rpl3l ^@ http://purl.uniprot.org/uniprot/E9PWZ3 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the universal ribosomal protein uL3 family.|||Component of the large ribosomal subunit (LSU). Part of a LSU subcomplex, the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11. Interacts with NVL in an ATP-dependent manner. Interacts with RRP1B (By similarity). Interacts with IPO5, IPO7 and KPNB1; these interactions may be involved in RPL5 nuclear import for the assembly of ribosomal subunits (By similarity). Interacts with RRP1B (By similarity).|||Expression in skeletal muscle is down-regulated in response to a hypertrophic stimulus.|||Expression is restricted to striated muscles.|||Heart- and skeletal muscle-specific component of the ribosome, which regulates muscle function (PubMed:26684695, PubMed:34081545, PubMed:36517592). Component of the large ribosomal subunit in striated muscle cells: replaces the RPL3 paralog in the ribosome in these cells (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Inhibits myotube growth and muscle function (PubMed:26684695, PubMed:34081545). http://togogenome.org/gene/10090:Pdia6 ^@ http://purl.uniprot.org/uniprot/Q3TML0|||http://purl.uniprot.org/uniprot/Q922R8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein disulfide isomerase family.|||Cell membrane|||Endoplasmic reticulum lumen|||May function as a chaperone that inhibits aggregation of misfolded proteins (PubMed:24508390). Negatively regulates the unfolded protein response (UPR) through binding to UPR sensors such as ERN1, which in turn inactivates ERN1 signaling (By similarity). May also regulate the UPR via the EIF2AK3 UPR sensor (By similarity). Plays a role in platelet aggregation and activation by agonists such as convulxin, collagen and thrombin (By similarity).|||Melanosome|||Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with MICA on the surface of tumor cells, leading to MICA disulfide bond reduction which is required for its release from tumor cells. Interacts with ITGB3 following platelet stimulation. Interacts with ERN1; the interaction is direct. Interacts with EIF2AK3. http://togogenome.org/gene/10090:Epb41l3 ^@ http://purl.uniprot.org/uniprot/Q9WV92 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Cell membrane|||Cytoplasm|||Detected in brain (at protein level). Highest expression in brain, lower in testis, adrenal gland, heart and kidney. Also present in muscle and epithelial cells. Isoform 1 is expressed in brain, isoform 2 is expressed in heart and isoform 3 is mostly expressed in kidney but also in heart and brain. Isoform 6 seems to be most abundant in kidney while isoform 4 and isoform 5 are predominantly expressed in heart and brain.|||Has the complete spectrin--actin-binding (SAB) domain and fully interacts with spectrin and actin.|||Inferred from the cDNA sequence of Ref.2.|||Interacts (via FERM domain) with CADM1. Interacts (via FERM domain) with PRMT3; the interaction is direct and inhibits the protein-arginine N-methyltransferase activity of PRMT3. Interacts with PRMT5. Interacts with PRMT6.|||The complete SAB domain is present only in the heart-specific isoforms (isoform 2 and isoform 5).|||Tumor suppressor that inhibits cell proliferation and promotes apoptosis. Modulates the activity of protein arginine N-methyltransferases, including PRMT3 and PRMT5 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Defb37 ^@ http://purl.uniprot.org/uniprot/Q7TMD2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Only expressed in epididymis (corpus and cauda).|||Secreted http://togogenome.org/gene/10090:Fthl17d ^@ http://purl.uniprot.org/uniprot/Q3SXD1 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Farp2 ^@ http://purl.uniprot.org/uniprot/Q91VS8 ^@ Domain|||Function|||Induction|||Subunit|||Tissue Specificity ^@ Detected in adult brain, lung and testis. Detected in embryonic hippocampus and brain cortex.|||Functions as guanine nucleotide exchange factor that activates RAC1. May have relatively low activity (PubMed:23375260, PubMed:20702777). Plays a role in the response to class 3 semaphorins and remodeling of the actin cytoskeleton. Plays a role in TNFSF11-mediated osteoclast differentiation, especially in podosome rearrangement and reorganization of the actin cytoskeleton. Regulates the activation of ITGB3, integrin signaling and cell adhesion.|||Interacts with PLXNA1. Interaction with PLXNA1 or PIP5K1C lowers its guanine nucleotide exchange activity. Dissociates from PLXNA1 when SEMA3A binds to the receptor. Interacts with PIP5K1C via its FERM domain. The interaction with PIP5K1C is enhanced by SEMA3A binding. Interacts with RAC1.|||Intramolecular interaction between the DH domain and the PH domains can stabilize the protein in an autoinhibited conformation.|||Up-regulated by TNFSF11. http://togogenome.org/gene/10090:Glipr2 ^@ http://purl.uniprot.org/uniprot/Q9CYL5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CRISP family.|||Golgi apparatus membrane|||Homodimer. Interacts with CAV1 (By similarity). http://togogenome.org/gene/10090:Sidt2 ^@ http://purl.uniprot.org/uniprot/Q3U1L8|||http://purl.uniprot.org/uniprot/Q8CIF6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SID1 family.|||Cell membrane|||Glycosylated.|||Interacts with adapter protein complex 1 (AP-1) and AP-2, but not AP-3 and AP-4 (PubMed:28724756). Interacts with LAMP2 (PubMed:27046251).|||Knockout mice demonstrate a statistically significant departure from Mendel's law, but there is no significant differences in their weights or appearance as compared to wild-type controls as newborns. At 5 weeks of age, male mice show reduced weight and size as compared to control animals. This phenotype is not observed in females. Mutant animals exhibit increased fasting glucose levels and impaired glucose tolerance, probably due to impaired insulin granule exocytosis by pancreatic islet cells (PubMed:23776622). At 3 months of age, serum triglyceride and free fatty acid levels increase in knockout mice fed on normal chow. Mice gradually develop hepatic steatosis, with varying degrees of inflammatory changes (PubMed:27233614).|||Lysosome membrane|||Mediates the translocation of RNA and DNA across the lysosomal membrane during RNA and DNA autophagy (RDA), a process in which RNA and DNA is directly imported into lysosomes in an ATP-dependent manner, and degraded (PubMed:27046251, PubMed:27846365, PubMed:28724756). Involved in the uptake of single-stranded oligonucleotides by living cells, a process called gymnosis (PubMed:28277980). In vitro, mediates the uptake of linear DNA more efficiently than that of circular DNA, but exhibits similar uptake efficacy toward RNA and DNA (PubMed:27846365). Binds long double-stranded RNA (dsRNA) (500 - 700 base pairs), but not dsRNA shorter than 100 bp (PubMed:26067272).|||Membrane|||Widely expressed, including in the liver, brain and kidney (at protein level). http://togogenome.org/gene/10090:Cfap298 ^@ http://purl.uniprot.org/uniprot/Q8BL95 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CFAP298 family.|||Cytoplasm|||Interacts with ZMYND10.|||Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly. Seems to be important for initiation rather than maintenance of cilium motility. Required for correct positioning of cilia at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway. May suppress canonical Wnt signaling activity.|||cilium basal body http://togogenome.org/gene/10090:Ly6g6c ^@ http://purl.uniprot.org/uniprot/Q9Z1Q4 ^@ PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Highly expressed at the leading edges of cells, on filopodia.|||Monomer.|||N-glycosylated. http://togogenome.org/gene/10090:Or14j2 ^@ http://purl.uniprot.org/uniprot/Q8VEU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zcchc4 ^@ http://purl.uniprot.org/uniprot/Q08EK6|||http://purl.uniprot.org/uniprot/Q8BKW4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZCCHC4 family.|||Cytoplasm|||Interacts with components of the ASC-1 complex TRIP4, ASCC1, ASCC2 and ASCC3. Interact with AHCYL1 and AHCYL2. Interact with YTHDC2.|||The regulatory loop blocks the catalytic center by bridging the methyltransferase domain and the C-terminal CCHC-type zinc finger, resulting in an autoinhibitory conformation.|||nucleolus|||rRNA N6-methyltransferase that specifically methylates the adenine in position 4220 of 28S rRNA. N6-methylation of adenine(4220) in 28S rRNA is required for translation. http://togogenome.org/gene/10090:Tsfm ^@ http://purl.uniprot.org/uniprot/Q9CZR8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome.|||Belongs to the EF-Ts family.|||Mitochondrion http://togogenome.org/gene/10090:Cox6c ^@ http://purl.uniprot.org/uniprot/Q9CPQ1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-61 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the cytochrome c oxidase subunit 6c family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Glra2 ^@ http://purl.uniprot.org/uniprot/Q3UTL8|||http://purl.uniprot.org/uniprot/Q7TNC8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA2 sub-subfamily.|||Cell membrane|||Cell projection|||Detected in the retina inner plexiform layer (at protein level) (PubMed:15329889). Detected in neonate retina. Detected in brain (PubMed:21924294). Detected in spinal cord, with higher levels in the dorsal horn (PubMed:16847326, PubMed:21924294).|||Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine. Channel opening is also triggered by taurine and beta-alanine. Plays a role in synaptic plasticity (PubMed:26370147). Contributes to the generation of inhibitory postsynaptic currents, and is involved in the down-regulation of neuronal excitability. Plays a role in cellular responses to ethanol.|||Homopentamer (in vitro). Interacts with GLRB. Heteropentamer composed of GLRA2 and GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different.|||Loss of glycine-induced currents in cortical neurons from 17 dpc embryos. Still, mutant mice are born at the expected Mendelian rate, are healthy and fertile. No effect on glycine-induced currents in cortical neurons from seven day old mice (PubMed:16847326). Baseline nociception is not changed, but mutant mice show increased hyperalgesia in response to mechanical stimuli during later stages of inflammation caused by zymosan injection (PubMed:21924294). Knockout mice show impaired learnig, short- and long-term memory deficits, and impaired long-term potentiation in the prefrontal cortex. Locomotor activity, motor coordination, and social behavior are normal (PubMed:26370147).|||Membrane|||Postsynaptic cell membrane|||Synapse|||Synaptic cell membrane|||The alpha subunit binds strychnine. http://togogenome.org/gene/10090:Ptx3 ^@ http://purl.uniprot.org/uniprot/P48759 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homooctamer; disulfide-linked (By similarity). Binds to C1q.|||Plays a role in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility.|||Secreted http://togogenome.org/gene/10090:Unc93a2 ^@ http://purl.uniprot.org/uniprot/B2RWK3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the unc-93 family.|||Membrane http://togogenome.org/gene/10090:Gng3 ^@ http://purl.uniprot.org/uniprot/P63216 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in brain. Low levels in testis.|||Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma. Forms a complex with GNAO1 and GNB1. Interacts with SCN8A.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Clcc1 ^@ http://purl.uniprot.org/uniprot/A2AEM2|||http://purl.uniprot.org/uniprot/Q99LI2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chloride channel MCLC family.|||Embryonic lethal.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with mitochondrial protein PIGBOS1 (via C-terminus); the interaction occurs at the mitochondria-associated endoplasmic reticulum (ER) membrane, a zone of contact between the ER and mitochondrial membranes, but does not appear to play a role in ER-mitochondria tethering and is not affected by ER stress (By similarity). Interacts with CALR (By similarity).|||Membrane|||Nucleus membrane|||Seems to act as a chloride ion channel (By similarity). Plays a role in retina development (PubMed:30157172). http://togogenome.org/gene/10090:Gbp6 ^@ http://purl.uniprot.org/uniprot/A0A8Q0QEH4|||http://purl.uniprot.org/uniprot/Q3U8G5 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. http://togogenome.org/gene/10090:Gria2 ^@ http://purl.uniprot.org/uniprot/Q4LG64 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. http://togogenome.org/gene/10090:Slurp1 ^@ http://purl.uniprot.org/uniprot/Q9Z0K7 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated in the cornea under pro-inflammatory conditions.|||Expressed in skin, eye, whole lung, trachea, esophagus and stomach (PubMed:14721776). Widely expressed in various tissues including spleen and thymus but not pancreas. Expressed in macrophages, dendritic cells, T and B cells (PubMed:17286989). Expressed in lung specifically in ciliated bronchial epithelial cells (at protein level). Expression is decreased in lungs of asthmatic model mice(PubMed:19396877, PubMed:20621062). Expressed in the cornea (PubMed:23139280).|||Has an antitumor activity. Was found to be a marker of late differentiation of the skin. Implicated in maintaining the physiological and structural integrity of the keratinocyte layers of the skin. In vitro down-regulates keratinocyte proliferation; the function may involve the proposed role as modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-7-dependent nAChR currents in an allosteric manner (By similarity). In T cells may be involved in regulation of intracellular Ca(2+) signaling (PubMed:17286989). Seems to have a immunomodulatory function in the cornea. The function may implicate a possible role as a scavenger receptor for PLAU thereby blocking PLAU-dependent functions of PLAUR such as in cell migration and proliferation (PubMed:23139280, PubMed:25168896).|||Homodimer (By similarity). Interacts with PLAU (PubMed:25168896). Interacts with CHRNA7.|||Secreted|||Severe palmoplantar keratoderma, reduced adiposity, protection from obesity on a high-fat diet, low plasma lipid levels, and neuromuscular abnormality (hind-limb clasping). http://togogenome.org/gene/10090:Pabir3 ^@ http://purl.uniprot.org/uniprot/Q9D5J5 ^@ Similarity ^@ Belongs to the FAM122 family. http://togogenome.org/gene/10090:Tox4 ^@ http://purl.uniprot.org/uniprot/Q8BU11 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82 and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS (By similarity). Interacts with FOXO1 and CREB1 (increased by cAMP); FOXO1 and CREB1 are required for full induction of TOX4-dependent activity and the interactions are inhibited by insulin (PubMed:34914893).|||Conditional knockout in liver lead to no 10% reduction of glucose levels after 4 hours of fasting with an improvement of glucose tolerance and an increased insulin sensitivity.|||In liver, expression is increased upon high fat diet.|||In liver, recruited to target gene promoters following treatment with dexamethasone and cAMP. Binding is decreased in presence of insulin.|||Nucleus|||Transcription factor that modulates cell fate reprogramming from the somatic state to the pluripotent and neuronal fate (PubMed:31519808). Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (By similarity). In liver, controls the expression of hormone-regulated gluconeogenic genes such as G6PC1 and PCK1. This regulation is independent of the insulin receptor activation (PubMed:34914893). http://togogenome.org/gene/10090:Zfp637 ^@ http://purl.uniprot.org/uniprot/Q80V23 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Snrpb ^@ http://purl.uniprot.org/uniprot/P27048 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP SmB/SmN family.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (By similarity). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:19470752). Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP (By similarity). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (PubMed:19470752). Interacts with TDRD3 and SNUPN (By similarity). Interacts with PRMT5; interaction leads to its symmetric arginine dimethylation (PubMed:28263986). Interacts with TDRD6; interaction promotes association with PRMT5 (PubMed:28263986). Interacts with SMN1; the interaction is direct (By similarity).|||Methylated by PRMT5 (PubMed:28263986). Arg-108 and Arg-112 are dimethylated, probably to asymmetric dimethylarginine (By similarity).|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:28263986). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (By similarity). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (PubMed:19470752).|||cytosol http://togogenome.org/gene/10090:Jade1 ^@ http://purl.uniprot.org/uniprot/Q6ZPI0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JADE family.|||Chromosome|||Component of the HBO1 complex composed at least of ING4 or ING5, KAT7/HBO1, MEAF6, and one of JADE1, JADE2 and JADE3. Interacts with NPHP4.|||Cytoplasm|||Expressed from 6.5 dpc. From 12.5 to 15.5 dpc, expressed in the nervous system and developing muscles.|||Highly expressed in kidney. Also present in liver (at protein level).|||Mice are viable and fertile, and show no visible phenotype.|||Nucleus|||Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac), regulating DNA replication initiation, regulating DNA replication initiation. May also promote acetylation of nucleosomal histone H4 by KAT5. Promotes apoptosis. May act as a renal tumor suppressor. Negatively regulates canonical Wnt signaling; at least in part, cooperates with NPHP4 in this function.|||The 2 PHD-type zinc fingers are required for transcriptional activity.|||cilium basal body http://togogenome.org/gene/10090:Acrbp ^@ http://purl.uniprot.org/uniprot/Q3V140 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acrosomal protein that maintains proacrosin (pro-ACR) as an enzymatically inactive zymogen in the acrosome. Involved also in the acrosome formation.|||Binds pro-ACR. Does not bind the mature form of ACR.|||Deficient male and female are normal in behavior, body size, and health condition. Females exhibit normal fertility. However, males exhibit a severely reduced fertility. The acrosomal structure of spermatids is severely deformed at the later steps of spermiogenesis.|||Degraded in elongating spermatid.|||Maintains pro-ACR as an enzymatically inactive zymogen in the acrosome until acrosomal exocytosis (PubMed:27303034). Partially contributes also to the assembly of acrosomal proteins to form an acrosomal granule (PubMed:27303034).|||Phosphorylated on Tyr residues in capacitated sperm.|||Rodent specific isoform that participates in the formation of the acrosomal granule into the center of the acrosomal vesicle during early spermiogenesis (PubMed:27303034). In the fertilization process promotes ACR release from the acrosome during acrosomal exocytosis (PubMed:27303034).|||Secreted|||Synthesized as a 60-kDa precursor in pachytene spermatocytes, postmeiotic spermatocytes and haploid spermatids and is processed into the mature protein in elongating spermatids.|||Testis-specific (at protein level). Detected in pachytene spermatocytes and in haploid spermatids and in elongating spermatids.|||Testis-specific. Detected in pachytene spermatocytes and round spermatids but absent in elongating spermatids. Produced specifically in rodents.|||The N-terminus is blocked.|||acrosome http://togogenome.org/gene/10090:Slc25a33 ^@ http://purl.uniprot.org/uniprot/Q3TZX3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial transporter that imports/exports pyrimidine nucleotides into and from mitochondria. Selectively transports uridine, thymidine, guanosine, cytosine and inosine (deoxy)nucleoside di- and triphosphates by an antiport mechanism (By similarity). May import (deoxy)nucleoside triphosphates in exchange for intramitochondrial (deoxy)nucleoside diphosphates, thus providing precursors necessary for de novo synthesis of mitochondrial DNA and RNA while exporting products of their catabolism (By similarity). Participates in mitochondrial genome maintenance, regulation of mitochondrial membrane potential and mitochondrial respiration (By similarity). Upon INS or IGF1 stimulation regulates cell growth and proliferation by controlling mitochondrial DNA replication and transcription, the ratio of mitochondria-to nuclear-encoded components of the electron transport chain resulting in control of mitochondrial ROS production (PubMed:17596519). Participates in dendritic cell endocytosis and may associate with mitochondrial oxidative phosphorylation (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Amn ^@ http://purl.uniprot.org/uniprot/Q99JB7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble form arises by proteolytic removal of the membrane anchor.|||Apical cell membrane|||Cell membrane|||Detected in primitive endoderm at 4.5 dpc, and on the apical surface of the visceral endoderm from 5.5 dpc to 8.5 dpc. Expressed in mesonephric tubules at 11.5-12.5 dpc and in the metanephric kidney beginning at 14.5 dpc. Expressed in the intestine from 16.5 dpc.|||Endosome membrane|||Expressed in polarized epithelial cells which are specialized in resorption or transport, specifically kidney proximal tubules and intestinal epithelium.|||Full embryonic lethality at about 10.5 dpc with failure of primitive middle streak assembly and absence of trunk mesoderm formation.|||Interacts (via extracellular region) with CUBN/cubilin (PubMed:15342463). This gives rise to a huge complex containing one AMN chain and three CUBN chains (By similarity).|||Membrane-bound component of the endocytic receptor formed by AMN and CUBN. Required for normal CUBN glycosylation and trafficking to the cell surface (PubMed:15342463). The complex formed by AMN and CUBN is required for efficient absorption of vitamin B12 (By similarity). Required for normal CUBN-mediated protein transport in the kidney (PubMed:15342463).|||N-glycosylated.|||The complex formed by AMN and CUBN is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains.|||The role of Amn in embryonic development seems to be species specific. In mice, null mutations lead to embryonic lethality. Human mutations give rise to much milder symptoms.|||coated pit http://togogenome.org/gene/10090:Nalf2 ^@ http://purl.uniprot.org/uniprot/A2BDP1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NALF family.|||Membrane|||Probable component of the NALCN channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability. http://togogenome.org/gene/10090:Lrrc25 ^@ http://purl.uniprot.org/uniprot/Q8K1T1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with RIGI. Interacts with SQSTM1. Interacts with p65/RELA; this interaction promotes the degradation of RELA through autophagy.|||Membrane|||Plays a role in the inhibition of RLR-mediated type I interferon signaling pathway by targeting RIGI for autophagic degradation. Interacts specifically with ISG15-associated RIGI to promote interaction between RIGI and the autophagic cargo receptor p62/SQSTM1 to mediate RIGI degradation via selective autophagy. Plays also a role in the inhibition of NF-kappa-B signaling pathway and inflammatory response by promoting the degradation of p65/RELA. http://togogenome.org/gene/10090:Or5h19 ^@ http://purl.uniprot.org/uniprot/E9QNM5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Klri2 ^@ http://purl.uniprot.org/uniprot/Q5DT36 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in natural killer (NK) cells.|||Heterodimer with KLRE1.|||Lectin-like receptor for natural killer (NK) cells. Heterodimer formation with KLRE1 mediates NK cell cytolytic activity. http://togogenome.org/gene/10090:Spata24 ^@ http://purl.uniprot.org/uniprot/Q6P926 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPATA24 family.|||Binds DNA with high affinity but does not bind to TATA boxes. Synergises with GMNN and TBP in activation of TATA box-containing promoters and with GMNN and TBPL1 in activation of the NF1 TATA-less promoter. May play a role in cytoplasm movement and removal during spermiogenesis.|||Cytoplasm|||Homodimer. Interacts with CBX3, CBX5, GMNN, GTF2B, TBPL1 and the polycomb proteins PHCF2, RNF2 and SCMH1 but not with CBX1 or PCGF2.|||In the embryo, abundant at 7.5 dpc and 8.5 dpc with higher levels at 9.5 dpc, 10.5 dpc and 11.5 dpc. Expression is low during the first two weeks after birth, increases during the third week and remains elevated in 4-week-old and adult mice. During spermatogenesis, expressed in spermatocytes mainly from zygotene to meiotic metaphase divisions and increases post-meiotically in round spermatids. Expression decreases in stage IV spermatids.|||Testis-specific (at protein level).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Tph2 ^@ http://purl.uniprot.org/uniprot/Q8CGV2 ^@ Similarity|||Tissue Specificity ^@ Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.|||Expressed in brain. http://togogenome.org/gene/10090:Fbxo9 ^@ http://purl.uniprot.org/uniprot/Q8BK06 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Interacts with TTI1 and TELO2; when TTI1 and TELO2 are phosphorylated by CK2.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins and plays a role in several biological processes such as cell cycle, cell proliferation, or maintenance of chromosome stability. Ubiquitinates mTORC1-bound TTI1 and TELO2 when they are phosphorylated by CK2 following growth factor deprivation, leading to their degradation. In contrast, does not mediate ubiquitination of TTI1 and TELO2 when they are part of the mTORC2 complex. As a consequence, mTORC1 is inactivated to restrain cell growth and protein translation, while mTORC2 is the activated due to the relief of feedback inhibition by mTORC1 (By similarity). Plays a role in maintaining epithelial cell survival by regulating the turn-over of chromatin modulator PRMT4 through ubiquitination and degradation by the proteasomal pathway (By similarity). Regulates also PPARgamma stability by facilitating PPARgamma/PPARG ubiquitination and thereby plays a role in adipocyte differentiation (PubMed:23643813, PubMed:27197753). http://togogenome.org/gene/10090:Pex2 ^@ http://purl.uniprot.org/uniprot/P55098|||http://purl.uniprot.org/uniprot/Q91YZ5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pex2/pex10/pex12 family.|||Component of the PEX2-PEX10-PEX12 retrotranslocation channel, composed of PEX2, PEX10 and PEX12.|||E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (By similarity). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX2 also regulates peroxisome organization by acting as a E3 ubiquitin-protein ligase (By similarity). PEX2 ubiquitinates PEX5 during its passage through the retrotranslocation channel: catalyzes monoubiquitination of PEX5 at 'Cys-11', a modification that acts as a signal for PEX5 extraction into the cytosol (By similarity). Required for pexophagy in response to starvation by mediating ubiquitination of peroxisomal proteins, such as PEX5 and ABCD3/PMP70 (By similarity). Also involved in the response to reactive oxygen species (ROS) by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of PNPLA2/ATGL, thereby regulating lipolysis (PubMed:34903883).|||Forms intramolecular and intermolecular disulfide bonds in response to reactive oxygen species (ROS), promoting higher stability.|||Membrane|||Mice in a C57BL/6J x 129/Sv strain background die several hours after birth (PubMed:9382874). Mutant mice do not feed and are hypoactive and markedly hypotonic (PubMed:9382874). Cells show defects in peroxisomes, characterized by an accumulation of very long chain fatty acids in plasma and deficient erythrocyte plasmalogens (PubMed:9382874). A significant proportion of mice in a Swiss Webster x 129/SvEv strain background survive 7-14 postnatal days (PubMed:12746876). Surviving mice display defects in cerebellar growth, characterized by a reduced granule neuron population, abnormal Purkinje cell dendrite development (PubMed:12746876). Peroxisome deficiency increases cell death in the developing cerebellum (PubMed:12746876). Defects in peroxisomes cause impaired hepatic cholesterol homeostasis (PubMed:14673138, PubMed:19110480). Peroxisome deficiency activates hepatic endoplasmic reticulum stress pathways, such as the integrated stress response (ISR), leading to dysregulation of the endogenous sterol response mechanism and subsequent SREBF2 activation (PubMed:19110480, PubMed:22441164). Conditional deletion in brain of adult mice leads to impaired BDNF signaling, resulting in memory defects (PubMed:33163488).|||Peroxisome membrane|||The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex. http://togogenome.org/gene/10090:Unc13d ^@ http://purl.uniprot.org/uniprot/B2RUP2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A truncating mutation is the cause of the jinxed phenotype (jinx), a chemically-induced mutation that make mice susceptible to murine cytomegalovirus (MCMV). It is a mouse model of human type 3 familial hemophagocytic lymphohistiocytosis. Affected mice produce a truncated protein that lack the second of the C2 domains and part of the second MHD domain. In jinx homozygotes, activated NK cells and cytotoxic T-lymphocytes (CTLs) fail to degranulate, although they retain the ability to produce cytokines. Mice do not spontaneously develop clinical features of hemophagocytic lymphohistiocytosis (HLH), but do so when infected with lymphocytic choriomeningitis virus (LCMV), exhibiting hyperactivation of CTLs and antigen-presenting cells, and inadequate restriction of viral proliferation. In contrast, neither Listeria monocytogenes nor MCMV induce the syndrome.|||Belongs to the unc-13 family.|||Cytoplasm|||Interacts with RAB27A and DOC2A (PubMed:18354201). Both RAB27A and DOC2A can simultaneously bind UNC13D (PubMed:18354201). Interacts with RhoG; the interaction increases RhoG affinity to the membrane lipids, targets Unc13d to membrane lipids and facilitates cytotoxic granule (CG) docking to the plasma membrane (By similarity).|||Late endosome|||Lysosome|||Mast cells.|||Membrane|||Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis (By similarity). Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.|||Recycling endosome|||The MHD1 and MHD2 domains mediate localization on recycling endosomes and lysosome. http://togogenome.org/gene/10090:Tbc1d21 ^@ http://purl.uniprot.org/uniprot/Q9D9D3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a GTPase-activating protein for Rab family protein (s) (PubMed:30360518). Essential for the establishment of male fertility, and is required for both the production of normal sperm number and sperm function (PubMed:32976492). Plays an important role in the formation of intact mitochondria, outer dense fibers and axoneme within the sperm tail (PubMed:32976492). Essential for sperm mitochondrial sheath formation and for the interactions of ARMC12 with VDAC2 and VDAC3 (PubMed:33536340). May be involved in acrosome formation and cytoskeletal reorganization during spermiogenesis, possibly by regulating RAB3A activity (PubMed:21128978).|||Detected from postnatal day 35 onward.|||Expressed in testis, specifically in elongating and elongated spermatids (at protein level) (PubMed:21128978, PubMed:30360518, PubMed:33536340). Expressed in the sperm midpiece (at protein level) (PubMed:32976492, PubMed:33536340).|||Interacts with ACTB (PubMed:21128978). Interacts with ARMC12 (PubMed:33536340). Interacts with TOMM20 and DNAH7 (PubMed:32976492). Interacts with RAP1A (PubMed:30360518). Interacts with RAB10 (By similarity).|||Male mice are sterile, characterized by defects in sperm tail structure and diminished sperm motility (PubMed:32976492, PubMed:33536340). The mitochondria of the sperm-tail has an abnormal irregular arrangement, abnormal diameter, and structural defects and the axoneme structure of sperm tails is severely disturbed (PubMed:32976492). Sperm mitochondria cannot form a proper mitochondrial sheath at the subsequent mitochondrial compaction step, although they can coil around the flagellum (PubMed:33536340).|||acrosome|||cytoskeleton http://togogenome.org/gene/10090:Gpc3 ^@ http://purl.uniprot.org/uniprot/Q3TWB2|||http://purl.uniprot.org/uniprot/Q8CFZ4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glypican family.|||Cell membrane|||Cell surface proteoglycan (By similarity). Negatively regulates the hedgehog signaling pathway when attached via the GPI-anchor to the cell surface by competing with the hedgehog receptor PTC1 for binding to hedgehog proteins (PubMed:18477453, PubMed:23665349). Binding to the hedgehog protein SHH triggers internalization of the complex by endocytosis and its subsequent lysosomal degradation (PubMed:18477453). Positively regulates the canonical Wnt signaling pathway by binding to the Wnt receptor Frizzled and stimulating the binding of the Frizzled receptor to Wnt ligands (By similarity). Positively regulates the non-canonical Wnt signaling pathway (PubMed:15537637). Binds to CD81 which decreases the availability of free CD81 for binding to the transcriptional repressor HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (PubMed:23665349). Inhibits the dipeptidyl peptidase activity of DPP4 (By similarity). Plays a role in limb patterning and skeletal development by controlling the cellular response to BMP4 (PubMed:10964473). Modulates the effects of growth factors BMP2, BMP7 and FGF7 on renal branching morphogenesis (PubMed:11180950). Required for coronary vascular development (PubMed:19733558). Plays a role in regulating cell movements during gastrulation (By similarity).|||Cell surface proteoglycan.|||Cleaved intracellularly by a furin-like convertase to generate 2 subunits, alpha and beta, which remain associated through disulfide bonds and are associated with the cell surface via the GPI-anchor. This processing is essential for its role in inhibition of hedgehog signaling. A second proteolytic event may result in cleavage of the protein on the cell surface, separating it from the GPI-anchor and leading to its shedding from the cell surface.|||Heterodimer; disulfide-linked (By similarity). Cleavage by a furin-like convertase results in production of alpha and beta chains which form a disulfide-linked heterodimer (By similarity). Interacts with DPP4 (By similarity). Interacts with FGF2 (By similarity). Interacts with WNT5A (By similarity). Also interacts with WNT3A and WNT7B (By similarity). Interacts with hedgehog protein SHH; the heparan sulfate chains are not required for the interaction (PubMed:18477453). Also interacts with hedgehog protein IHH (PubMed:23665349). Interacts with CD81 (PubMed:23665349). Interacts with Wnt receptors FZD4, FZD7 and FZD8; the heparan sulfate chains are required for the interaction (By similarity).|||In the developing limb, absent from the apical epidermal ridge at 11 dpc but highly expressed in the underlying mesenchyme (PubMed:10964473). Expression in the mesenchyme at this stage is asymmetric with highest levels in the regions of the distal mesenchyme within the progress zone and within the proximal anterior and posterior limb bud (PubMed:10964473). At later developmental stages including 12.5 and 13.5 dpc, expression is restricted to the interdigital webs and the regions of chondrocytic differentiation of the developing bones (PubMed:10964473). In the embryonic kidney, expressed in both the ureteric bud and mesenchymal cells as early as 13.5 dpc (PubMed:11180950). Expression at 16.5 dpc is similar to that at 13.5 dpc but decreases by 18.5 dpc (PubMed:11180950).|||O-glycosylated; contains heparan sulfate and/or chondroitin sulfate.|||Perinatal death, developmental overgrowth, cystic and dyplastic kidneys, abnormal lung development and ventral wall closure defects (PubMed:10402475, PubMed:10964473). A proportion of mutants also display mandibular hypoplasia and an imperforate vagina (PubMed:10402475). There is an early and persistent abnormality in ureteric bud development in the kidney due to increased cell proliferation (PubMed:10402475). In the developing kidney, cell proliferation is increased threefold in cortical collecting duct cells and apoptosis is increased 16-fold in medullary collecting duct cells (PubMed:11180950). High incidence of congenital cardiac malformations including ventricular septal defects, common atrioventricular canal, double outlet right ventricle and presence of coronary artery fistulas (PubMed:19733558). Elevated levels of hedgehog pathway proteins Gli1 and Ptc1, indicative of activation of the hedgehog pathway and increased levels of Shh (PubMed:18477453). Reduced non-canonical Wnt signaling (PubMed:15537637). Similar levels of tissue and serum Igf2 to wild-type mice (PubMed:10402475). http://togogenome.org/gene/10090:Naf1 ^@ http://purl.uniprot.org/uniprot/E9QJT2|||http://purl.uniprot.org/uniprot/Q3UMQ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAF1 family.|||Cytoplasm|||During assembly of the complex, component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs) which contains NOLA2/NHP2, NOLA3/NOP10, NAF1 and DKC1/NOLA4. Interacts directly with DKC1/NOLA4 (By similarity).|||Nucleus|||RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex and disappears during maturation of the complex and is replaced by NOLA1/GAR1 to yield mature H/ACA snoRNPs complex. Probably competes with NOLA1/GAR1 for binding with DKC1/NOLA4 (By similarity). http://togogenome.org/gene/10090:Traip ^@ http://purl.uniprot.org/uniprot/Q8VIG6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Belongs to the TRAIP family.|||Chromosome|||Cytoplasm|||Detected in testis and thymus, and at lower levels in spleen.|||E3 ubiquitin ligase required to protect genome stability in response to replication stress (PubMed:33590678). Acts as a key regulator of interstrand cross-link repair, which takes place when both strands of duplex DNA are covalently tethered together, thereby blocking replication and transcription (By similarity). During mitosis, controls the choice between the two pathways of replication-coupled interstrand-cross-link repair by mediating ubiquitination of MCM7 subunit of the CMG helicase complex (PubMed:33590678). Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3 (By similarity). If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase, enabling the Fanconi anemia DNA repair pathway (By similarity). Only catalyzes ubiquitination of MCM7 when forks converge (By similarity). Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: promotes ubiquitination of DPCs, leading to their degradation by the proteasome (By similarity). Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys-63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity (By similarity). The function in translesion synthesis is however controversial (By similarity). Acts as a regulator of the spindle assembly checkpoint (By similarity). Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF (PubMed:17544371, PubMed:22945920). Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation (By similarity).|||Early embryonic lethality due to proliferation defects and excessive cell death (PubMed:17927961). TRAIP knockdown substantially increases LPS- and poly(I:C)-induced IFN-production in mouse peritoneal macrophages at both mRNA and protein levels (PubMed:22945920).|||Expressed during oocytes meiosis.|||Interacts (via PIP-box) with PCNA (By similarity). Binds TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6 is part of the receptor-TRAF signaling complex (PubMed:17544371, PubMed:9104814). May interact with CYLD; the C-terminus interacts with CYLD, however the interaction was not detected with the full-length protein (By similarity). Interacts with POLK and POLN (By similarity). Interacts with UIMC1 (By similarity).|||Sumoylated; sumoylation is required for nuclear localization. Sumoylation increases protein stability, possibly by preventing ubiquitination.|||nucleolus|||nucleoplasm|||perinuclear region http://togogenome.org/gene/10090:Erap1 ^@ http://purl.uniprot.org/uniprot/Q9EQH2 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney (By similarity).|||Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Endoplasmic reticulum membrane|||Monomer. May also exist as a heterodimer; with ERAP2. Interacts with RBMX (By similarity).|||N-glycosylated. http://togogenome.org/gene/10090:Marchf11 ^@ http://purl.uniprot.org/uniprot/D3YXE6|||http://purl.uniprot.org/uniprot/Q8CBH7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle membrane|||E3 ubiquitin-protein ligase that mediates polyubiquitination of CD4. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May play a role in ubuquitin-dependent protein sorting in developmenting spermatids.|||Interacts (YXXL motif) with AP1M1. Interacts (via PDZ-binding motif) with LIN7A. Interacts with unidentified fucose glycoproteins.|||Membrane|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Tes ^@ http://purl.uniprot.org/uniprot/Q921W7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the prickle / espinas / testin family.|||Cytoplasm|||focal adhesion http://togogenome.org/gene/10090:Niban3 ^@ http://purl.uniprot.org/uniprot/D3YZB0 ^@ Similarity ^@ Belongs to the Niban family. http://togogenome.org/gene/10090:Arel1 ^@ http://purl.uniprot.org/uniprot/Q8CHG5 ^@ Disruption Phenotype|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Autoubiquitinated in vitro in the presence of E2 enzyme UBE2D1/UBCH5A.|||Detected in brain, testis, heart, liver, lung and kidney with very low levels in skeletal muscle and spleen.|||E3 ubiquitin-protein ligase that catalyzes 'Lys-11'- or 'Lys-33'-linked polyubiquitin chains, with some preference for 'Lys-33' linkages (By similarity). E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (By similarity). Ubiquitinates SEPTIN4, DIABLO/SMAC and HTRA2 in vitro (By similarity). Modulates pulmonary inflammation by targeting SOCS2 for ubiquitination and subsequent degradation by the proteasome (PubMed:31578312).|||Interacts with SOCS2 (PubMed:31578312). Interacts (via HECT domain) with HTRA2, DIABLO/SMAC and SEPTIN4; in the cytoplasm following induction of apoptosis (PubMed:23479728).|||Mice show significant and stepwise decreases in indicators of inflammatory injury, such as bronchoalveolar lavage fluid protein concentration and cell count, as well as decreases in pro-inflammatory cytokine release. http://togogenome.org/gene/10090:Eras ^@ http://purl.uniprot.org/uniprot/Q7TN89 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Expressed in several undifferentiated mouse embryonic stem cell lines.|||Interacts with PIK3CD.|||Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Plays an important role in the tumor-like growth properties of embryonic stem cells. http://togogenome.org/gene/10090:Hp1bp3 ^@ http://purl.uniprot.org/uniprot/Q3TEA8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ A central region that included the first H15 (linker histone H1/H5 globular) domain binds at the entry/exit site of the nucleosomal DNA.|||Chromosome|||Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity. May play a role in hypoxia-induced oncogenesis.|||Interacts (via PxVxL motif) with CBX5 (via Trp-174).|||Nucleus http://togogenome.org/gene/10090:Dync2i1 ^@ http://purl.uniprot.org/uniprot/Q8C761 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system. DYNC2I1 plays a major role in retrograde ciliary protein trafficking in cilia and flagella. Requires also to maintain a functional transition zone.|||Belongs to the dynein light intermediate chain family.|||Intermediate chain of the cytoplasmic dynein complex 2, a multisubunit complex, composed at least of eleven different proteins. The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the cytoplasmic dynein complex 2, but a subset of the light chains are also shared by dynein-1 and dynein-2 complexes. Interacts with DYNC2I2; their C-terminal domains each bind a copy of the heavy chain, and their extended N-terminal regions are held together by an array of light chain dimers. Interacts with DYNLT2B. Interacts (via the N-terminal half) with DYNLT2B-DYNLT1 dimer or with DYNLT2B-DYNLT3 dimer; this interaction is crucial for retrograde trafficking of ciliary proteins.|||centrosome|||cilium http://togogenome.org/gene/10090:Myo1h ^@ http://purl.uniprot.org/uniprot/A0A0J9YUC4 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Rps3a1 ^@ http://purl.uniprot.org/uniprot/P97351|||http://purl.uniprot.org/uniprot/Q564F3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated at Tyr-155 by PARP1 in presence of HPF1.|||Belongs to the eukaryotic ribosomal protein eS1 family.|||Component of the small ribosomal subunit (PubMed:36517592). Mature ribosomes consist of a small (40S) and a large (60S) subunit (PubMed:36517592). The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S) (PubMed:36517592). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S) (PubMed:36517592). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Binds with high affinity to IPO4. Interacts with DDIT3. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity). May play a role during erythropoiesis through regulation of transcription factor DDIT3 (PubMed:10713066).|||Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Binds with high affinity to IPO4. Interacts with DDIT3.|||Cytoplasm|||May play a role during erythropoiesis through regulation of transcription factor DDIT3.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Or5b124 ^@ http://purl.uniprot.org/uniprot/Q8VFQ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grcc10 ^@ http://purl.uniprot.org/uniprot/O35127 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UPF0456 family.|||Cytoplasm|||Detected as early as 10.5 dpc.|||In brain, may be required for corpus callosum development.|||Ubiquitously expressed, with higher expression in lung. http://togogenome.org/gene/10090:Cep131 ^@ http://purl.uniprot.org/uniprot/Q62036 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CEP131 family.|||By 5-azacytidine.|||Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation. In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation. In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner. Acts also as a negative regulator of BBSome ciliary trafficking (By similarity). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (PubMed:24415959). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability and centriole duplication in non-ciliogenic cells (By similarity). Involved in centriole duplication (PubMed:26297806). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (By similarity). Essential for maintaining proper centriolar satellite integrity (By similarity).|||Females grow normally and are healthy. Males display developing sperm flagella abnormalities resulting in infertility. Post-meiotic defects during spermatogenesis with abnormal morphology of elongating and elongated spermatids, including teratozoospermia, premature apoptosis, but without increase in DNA damage. Sperm are immotile with shortened and morphologically abnormal flagella, and altered intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking. Displays normal postnatal multiciliated airway epithelium. Lacks retinal degeneration and kidney cysts formations.|||Localized to the pre-acrosome region of round and elongated spermatids in testis but also present in ovary, brain and adipose tissue.|||MAPKAPK2-dependent phosphorylation at Ser-47 and Ser-78 occurs in response to cellular stress such as exposure to ultraviolet irradiation and promotes binding to 14-3-3 proteins which leads to cytoplasmic sequestration of CEP131 and blocks formation of new centriolar satellites (By similarity). Phosphorylation at Ser-78 mediated by PLK4 is essential for proper organization and integrity of centriolar satellites but is dispensable for its localization to centrioles and its function in ciliogenesis (By similarity).|||Self-associates (By similarity). Associates with the centriolar satellite BBSome protein complex (PubMed:24550735) Interacts with BBS4; the interaction limits BBS4 availability for association with the BBSome complex, and hence negatively regulates ciliary localization of the BBSome complex. Interacts with MIB1. Interacts with PCM1; the interaction increases in response to ultraviolet light (UV) radiation. Associates with microtubule; association to microtubule is reduced in response to cellular stress, such as UV stimulation, in a process that requires p38 MAP kinase signaling. Interacts with CEP290, DCTN1, MAP1LC3B, PCNT, PCM1 and CEP152 (By similarity). Interacts with 14-3-3 proteins following UV-induced phosphorylation by MAPKAPK2; this inhibits formation of novel centriolar satellites (By similarity). Interacts with SDCCAG8 (By similarity). Interacts with CCDC61 (By similarity). Interacts with PLK4 (By similarity).|||Transient cell cultured-based knock-down (by RNAi) of CEP131 leads to a reduction in ciliogenesis (PubMed:24415959). However, chronic absence of CEP131 following genetic deletion (knockout) shows that cilia develop and function normally in vivo. This suggests that CEP131 is not essential for ciliogenesis, except for the modified cilia of the developing sperm flagella, and that there is an alternative mechanism to compensate for the lack of CEP131 (PubMed:24415959).|||Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3 ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia formation. Monoubiquitination by MIB1 is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, resulting in ciliogenesis restoration (By similarity).|||Widely expressed during development, with strong expression in tissues with high levels of cilia-dependent developmental signaling such as the limbs, eyes, somite derivatives and brain. Significant amounts are found in the testis of 16 day old mice, at a late stage of pachytene spermatocytes when meiosis occurs. The level increases thereafter.|||acrosome|||centriolar satellite|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Or4c125 ^@ http://purl.uniprot.org/uniprot/Q8VGN0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prkce ^@ http://purl.uniprot.org/uniprot/P16054 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (By similarity).|||Cell membrane|||Cytoplasm|||Forms a ternary complex with TRIM63 and RACK1/GN2BL1 (By similarity). Can form a complex with PDLIM5 and N-type calcium channel (By similarity). Interacts with COPB1 (By similarity). Interacts with DGKQ (By similarity). Interacts with STAT3 (By similarity). Interacts with YWHAB (PubMed:18604201). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (By similarity). Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM (By similarity). Interacts with NLRP5/MATER (By similarity).|||Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation.|||Nucleus|||Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729 (By similarity). Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB.|||The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Snx6 ^@ http://purl.uniprot.org/uniprot/Q6P8X1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome membrane|||Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2. The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity (By similarity). Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, TGFB receptors, BACE1, BRMS1, PIP5K1C. Interacts with DCTN1; the association with DCTN1 is involved in movement of retromer-c ontaining vesicles toward the TGN. Interacts with PIM1; translocating SNX6 to the nucleus (By similarity). Interacts with CDKN1B and GIT1 (PubMed:18523162, PubMed:20228253).|||In vitro phosphorylated by PIM1; not affecting PIM1-dependent nuclear translocation (By similarity).|||Involved in several stages of intracellular trafficking. Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-membrane remodeling activity (By similarity). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptor IGF2R. May function as link between transport vesicles and dynactin. Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By similarity). In association with GIT1 involved in EGFR degradation (PubMed:18523162). Promotes lysosomal degradation of CDKN1B (PubMed:20228253). May contribute to transcription regulation (By similarity).|||Nucleus|||The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (By similarity).|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate. http://togogenome.org/gene/10090:Mcub ^@ http://purl.uniprot.org/uniprot/Q810S1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MCU (TC 1.A.77) family.|||Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (By similarity). Heterooligomer with MCU; this reduces MCU channel activity. Homooligomer.|||Detected in lung, brain and heart, and at lower levels in white fat, skeletal muscle and spleen. Detected at very low levels in kidney and liver.|||Mitochondrion inner membrane|||Negatively regulates the activity of MCU, the mitochondrial inner membrane calcium uniporter, and thereby modulates calcium uptake into the mitochondrion. Does not form functional calcium channels by itself. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways. http://togogenome.org/gene/10090:Rnf20 ^@ http://purl.uniprot.org/uniprot/Q5DTM8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BRE1 family.|||Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1) (PubMed:28453857). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively). It thereby plays a central role in histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes. Recruited to the MDM2 promoter, probably by being recruited by p53/TP53, and thereby acts as a transcriptional coactivator. Mediates the polyubiquitination of PA2G4 leading to its proteasome-mediated degradation.|||Component of the RNF20/40 complex (also known as BRE1 complex) probably composed of 2 copies of RNF20/BRE1A and 2 copies of RNF40/BRE1B. Interacts with UBE2E1/UBCH6. Interacts with p53/TP53 and WAC. Interacts with PAF1; the interaction mediates the association of the PAF1 and RNF20/40 complexes which is a prerequsite for recruitment of UBE2A/B. Interacts with PA2G4. Interacts with FBXL19 (PubMed:28453857).|||Nucleus http://togogenome.org/gene/10090:Trp53i13 ^@ http://purl.uniprot.org/uniprot/Q5F267 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Cytoplasm|||May act as a tumor suppressor. Inhibits tumor cell growth, when overexpressed (By similarity). http://togogenome.org/gene/10090:H2ac22 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Slc47a1 ^@ http://purl.uniprot.org/uniprot/Q8K0H1 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.|||Cell membrane|||Deficient mice are viable and fertile without any overt phenotypical or histological alterations. However, mice exhibit increased blood urea nitrogen, increased circulating creatinine, and abnormal metformin pharmacokinetics, including increased plasma and tissue metformin concentration with decreased kidney and liver metformin clearance.|||Mediates the efflux of cationic compounds such as the model cations, tetraethylammonium (TEA), the neurotoxin 1-methyl-4-phenylpyridinium (MPP), the platinum-based drugs cisplatin and oxaliplatin, the drugs procainamide, acyclovir and topotecan, or weak bases that are positively charged at physiological pH, such as cimetidine or the antidiabetic drug metformin.|||Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16641166, PubMed:19332510). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (By similarity). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (By similarity). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (By similarity).|||Predominantly expressed in kidney and liver (PubMed:24961373). Also expressed in various cells, including brain glia-like cells and capillaries, pancreatic duct cells, urinary bladder epithelium, adrenal gland cortex, heart, stomach, small intestine, thyroid gland, testes, alpha cells of the islets of Langerhans, Leydig cells, and vitamin A-storing Ito cells. Expressed in heart, stomach, small intestine, bladder, thyroid gland, adrenal gland and testes (at protein level). http://togogenome.org/gene/10090:Dagla ^@ http://purl.uniprot.org/uniprot/Q6WQJ1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Cell membrane|||Deficient mice are viable, fertile and display normal physiological behaviors (PubMed:20159446, PubMed:20147530). Deficient mice show 80-90% reductions in brain 2-AG as well as the downstream product arachidonic acid (AA), in particular in neurons and astrocytes (PubMed:20159446, PubMed:20147530, PubMed:26779719, PubMed:25466252). The endocannabinoid-mediated retrograde synaptic suppression of neurotransmitter release is absent in the cerebellum, hippocampus, and striatum of knockout mice (PubMed:20159446, PubMed:20147530). In addition, reduction in adult neurogenesis is observed in deficient mice in both the hippocampus and the subventricular zone (PubMed:20147530). DAGLA deletion increases anxiety-like and depressive behaviors (PubMed:25466252). Reduction in LPS-stimulated neuroinflammation is also observed in knockout mice (PubMed:26779719).|||Early endosome membrane|||Highly expressed by principal cells in the hippocampus. In embryonic brains, it is present in axonal tracts, while in adults it localizes to dendritic fields, correlating with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment. Concentrated in heads of dendritic spines throughout the hippocampal formation. Highly compartmentalized into a wide perisynaptic annulus around the postsynaptic density of axospinous contacts but not intrasynaptically (at protein level).|||Inhibited by 1,2,3-triazole urea covalent inhibitor KT172, DH376 and DO34 (PubMed:23103940, PubMed:26668358). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-784 and Ser-810 by CAMK2A (By similarity).|||Interacts (via C-terminal) with CAMK2A; leading to the phosphorylation and inhibition of DAGLA enzymatic activity (PubMed:23502535). Interacts (via PPXXF motif) with HOMER1 and HOMER2; this interaction is required for DAGLA membrane localization (PubMed:17584991).|||Phosphorylated at Ser-784 and Ser-810 by CAMK2A; phosphorylation by CAMK2A inhibits diacylglycerol lipase activity.|||Postsynaptic density membrane|||Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid (eCB), 2-arachidonoylglycerol (2-AG) (PubMed:17584991, PubMed:23103940). Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at the sn-2 position to biosynthesize 2-AG. Has negligible activity against other lipids including monoacylglycerols and phospholipids (PubMed:17584991). Plays a key role in regulating 2-AG signaling in the central nervous system (CNS) (PubMed:20159446, PubMed:20147530, PubMed:25466252, PubMed:26668358, PubMed:26779719). Controls the activity of 2-AG as a retrograde messenger at neuronal synapses (PubMed:20159446, PubMed:20147530, PubMed:26668358). Supports axonal growth during development and adult neurogenesis (PubMed:20147530). Plays a role for eCB signaling in the physiological regulation of anxiety and depressive behaviors (PubMed:25466252). Regulates also neuroinflammatory responses in the brain, in particular, LPS-induced microglial activation (PubMed:26779719).|||dendritic spine membrane http://togogenome.org/gene/10090:Cpxm2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0C4|||http://purl.uniprot.org/uniprot/Q9D2L5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although related to peptidase M14 family, lacks the active site residues and zinc-binding sites, suggesting that it has no carboxypeptidase activity.|||Belongs to the peptidase M14 family.|||Highly expressed in lung and kidney. Moderate expression in liver and brain, including the cerebral cortex, piriform cortex, nucleus of the lateral olfactory tract, hippocampus, habenular nucleus, and choroid plexus.|||May be involved in cell-cell interactions.|||Secreted http://togogenome.org/gene/10090:Ace ^@ http://purl.uniprot.org/uniprot/P09470|||http://purl.uniprot.org/uniprot/Q3TU20 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M2 family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 3 chloride ions per subunit.|||Cell membrane|||Cytoplasm|||Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (PubMed:7753170, PubMed:8642790, PubMed:9231832, PubMed:11723129, PubMed:12777443, PubMed:14757757, PubMed:16270063, PubMed:35201898). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:11303049). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (PubMed:9231832, PubMed:11303049, PubMed:14757757). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (By similarity). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (By similarity). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (PubMed:35201898). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (PubMed:35201898). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (PubMed:35201898). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:11303049). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By similarity). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (By similarity). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (By similarity). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (PubMed:11303049).|||Highly expressed in kidney and lung; not expressed in the liver (PubMed:16154999). In the brain, expressed in the cerebral cortex, hippocampus, cerebellum and basal ganglia/brainstem (PubMed:16154999). Highly expressed in dopamine receptor DRD1-expressing neurons in the dorsal striatum and the nucleus accumbens of the brain (PubMed:35201898).|||Isoform Testis-specific only binds 1 Zn(2+) ion per subunit.|||Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility (PubMed:1651914, PubMed:9482924). In contrast to somatic isoforms, only contains one catalytic domain (PubMed:16270063). Acts as a dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of substrates (PubMed:16270063). The identity of substrates that are needed for male fertility is unknown (PubMed:16270063). Isoform Testis-specific and isoform Somatic have distinct activities and cannot completely compensate for the loss of the other when expressed in somatic tissues or testis (PubMed:9664078, PubMed:10831599, PubMed:11723129, PubMed:12777443, PubMed:16270063). May also have a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety (PubMed:15665832). The GPIase activity was reported to be essential for the egg-binding ability of the sperm (PubMed:15665832). This activity is however unclear and has been challenged by other groups, suggesting that it may be indirect (PubMed:16270063).|||Mice display low blood pressure (hypotension), elevated serum potassium, anemia, urine concentration defects and gross renal structural defects (PubMed:8642790, PubMed:9231832, PubMed:11723129, PubMed:12777443). Male mice also have reduced fertility: sperm show defects in transport within the oviducts and in binding to zonae pellucidae (PubMed:7753170, PubMed:9482924). Mice also show impaired metabolism, characterized by increased energy expenditure, reduced fat mass and improved glucose clearance (PubMed:18443281). Expression of isoform Somatic in testis in knockout mice does not restore male fertility (PubMed:10831599). In contrast, expression of isoform Testis-specific in the sperm of knockout mice only restores fertility without curing other defects (PubMed:9664078). Isoform Testis-specific can substitute for isoform Somatic for normal kidney structure but not for normal blood pressure when expressed in vascular cells of knockout mice (PubMed:11723129, PubMed:12777443, PubMed:16270063).|||Mice lacking somatic isoform display normal male fertility.|||Monomer and homodimer; homodimerizes following binding to an inhibitor (By similarity). Interacts with calmodulin (CALM1, CALM2 or CALM3); interaction takes place in the cytoplasmic region and regulates phosphorylation and proteolytic cleavage (By similarity).|||Phosphorylated by CK2 on Ser-1305; which allows membrane retention (By similarity). Phosphorylated on tyrosine residues on its extracellular part, promoting cleavage by secretase enzymes and formation of the soluble form (Angiotensin-converting enzyme, soluble form) (By similarity).|||Produced following proteolytic cleavage by secretase enzymes that cleave the transmembrane form in the juxtamembrane stalk region upstream of the transmembrane region. Cleavage can take place at different sites of the juxtamembrane stalk region.|||Secreted|||Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region.|||Specifically expressed in spermatocytes, adult testis.|||The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat (PubMed:15665832, PubMed:35201898). The N-terminal catalytic domain, but not the C-terminal catalytic domain, is specifically inhibited by the phosphinic peptide RXP 407 (PubMed:11303049).|||The putative GPIase activity is nearly insensitive to captopril. http://togogenome.org/gene/10090:Calml4 ^@ http://purl.uniprot.org/uniprot/Q91WQ9 ^@ Similarity ^@ Belongs to the calmodulin family. http://togogenome.org/gene/10090:Ifrd1 ^@ http://purl.uniprot.org/uniprot/P19182 ^@ Caution|||Function|||Induction|||Similarity|||Subunit ^@ Belongs to the IFRD family.|||By mitogens such as TPA in 373 cells and by nerve growth factor in PC12 pheochromocytoma cells.|||Could play a role in regulating gene activity in the proliferative and/or differentiative pathways induced by NGF. May be an autocrine factor that attenuates or amplifies the initial ligand-induced signal.|||Interacts with PSIP1/LEDGF.|||Was originally thought to be interferon beta-2. http://togogenome.org/gene/10090:Capns1 ^@ http://purl.uniprot.org/uniprot/O88456 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||EF-hand domains are paired. EF-hand 1 is paired with EF-hand 2 and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand domain, left unpaired, does not bind the calcium but is responsible of the dimerization by EF-embrace. The first four EF-hand domains bind calcium, however it is not sure if the binding of EF-hand 4 to calcium is physiologically relevant.|||Embryonic lethality by 11.5 dpc, with indications of defects in both vasculogenesis and erythropoiesis.|||Homodimer or heterodimer of a large (catalytic) and a small (regulatory) subunit. In presence of calcium, the heterodimer dissociates (By similarity).|||Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Essential for embryonic development (PubMed:10825211).|||The contact of the 5th EF-hand domain from each monomer allows the formation of the homodimer and also appears to mediate the contact between the large catalytic subunit and small regulatory subunit for the formation of the heterodimer. http://togogenome.org/gene/10090:Plin4 ^@ http://purl.uniprot.org/uniprot/O88492 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the perilipin family.|||Cell membrane|||Cytoplasm|||Lipid droplet|||May play a role in triacylglycerol packaging into adipocytes. May function as a coat protein involved in the biogenesis of lipid droplets.|||Specifically expressed in white adipose tissue and also weakly detected in heart and skeletal muscle (at protein level).|||Up-regulated by PPARG and during adipocyte differentiation. http://togogenome.org/gene/10090:Vapa ^@ http://purl.uniprot.org/uniprot/Q9WV55 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.|||Cell membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and late endosomes via interaction with STARD3. In addition, mediates recruitment of VAPA to plasma membrane sites through OSBPL3 binding. The OSBPL3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface. With OSBPL3, may regulate ER morphology. May play a role in vesicle trafficking.|||Homodimer; disulfide-linked. Heterodimer with VAPB. Homotetramer. Interacts with VAMP1, VAMP2, STX1A, BET1, SEC22C and with the C-terminal domain of OCLN. Interacts (via MSP domain) with OSBPL1A (via FFAT motif) (By similarity). Interacts (via MSP domain) with ZFYVE27; may retain ZFYVE27 in the endoplasmic reticulum and regulate its function in cell projections formation (PubMed:24251978). Interacts with OSBP. Interacts (via C-terminus) with RSAD2/viperin (via C-terminus). Interacts with IFITM3. Interacts with OSBPL3 (phosphorylated form). Interacts with KIF5A in a ZFYVE27-dependent manner. Interacts (via MSP domain) with STARD3 (via phosphorylated FFAT motif); this interaction recruits VAPA to the endosome. Interacts with STARD3NL (via FFAT motif). Interacts with CERT1. Interacts with PLEKHA3 and SACM1L to form a ternary complex. Interacts with VPS13A (via FFAT motif). Interacts with RB1CC1 (via phosphorylated FFAT motif), MIGA2 (via phosphorylated FFAT motif), RMDN3 (via phosphorylated FFAT motif), KCNB1 (via phosphorylated FFAT motif) and KCNB2 (via phosphorylated FFAT motif) (By similarity).|||Nucleus membrane|||Ubiquitous.|||tight junction http://togogenome.org/gene/10090:Galr1 ^@ http://purl.uniprot.org/uniprot/P56479 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expression is detected in brain, spinal cord, heart and skeletal muscle.|||Receptor for the hormone galanin. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity.|||Three cysteine residues are found in the C-terminus, at least one of which may be palmitoylated. http://togogenome.org/gene/10090:Gabrd ^@ http://purl.uniprot.org/uniprot/P22933|||http://purl.uniprot.org/uniprot/Q14AH9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRD sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. There are five types of GABA(A) receptor subunits: alpha, beta, gamma, delta, and rho.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Tada2b ^@ http://purl.uniprot.org/uniprot/D3Z4Z0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Dnm1 ^@ http://purl.uniprot.org/uniprot/A0A0J9YUN4|||http://purl.uniprot.org/uniprot/P39053 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.|||Binds SH3GL1, SH3GL2 and SH3GL3 (By similarity). Interacts with SNX9 (By similarity). Interacts with PHOCN. Interacts with MYO1E (via SH3 domain). Interacts with SNX33 (via SH3 domain) (By similarity). Interacts with CAV1 and SH3GLB1. Interacts with PACSIN1, PACSIN2 and PACSIN3. Interacts with UNC119; leading to a decrease of DNM1 GTPase activity. Interacts with DIAPH1 (By similarity). Interacts with AMPH, BIN1 and SYNJ1 (By similarity).|||Cytoplasm|||Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes. Involved in receptor-mediated endocytosis (By similarity).|||Phosphorylated in response to EGF stimulation in cells expressing truncated EGFR.|||cytoskeleton http://togogenome.org/gene/10090:Tfrc ^@ http://purl.uniprot.org/uniprot/Q542D9|||http://purl.uniprot.org/uniprot/Q62351 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M28 family. M28B subfamily.|||Cell membrane|||Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (By similarity). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). Upon stimulation, positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (By similarity). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (By similarity). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (By similarity).|||Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway.|||Homodimer; disulfide-linked.|||Homodimer; disulfide-linked. Binds one transferrin molecule per subunit. Interacts with SH3BP4 (By similarity). Interacts with STEAP3; facilitates TFRC endocytosis in erythroid precursor cells (By similarity).|||Melanosome|||Membrane|||N- and O-glycosylated, phosphorylated and palmitoylated.|||Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of the JNK pathway and promotes mitochondrial fragmentation (By similarity). Stearoylation does not affect iron uptake (By similarity).|||Stearoylated. http://togogenome.org/gene/10090:Or10q1 ^@ http://purl.uniprot.org/uniprot/Q8VGP8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Galnt13 ^@ http://purl.uniprot.org/uniprot/A2RRI8|||http://purl.uniprot.org/uniprot/Q8CF93 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor (PubMed:12407114, PubMed:8618846, PubMed:27629416). Generates GalNAc-O-Ser/Thr structure also known as Tn antigen, which itself is immunogenic but also serves as a precursor for the synthesis of different mucin-type O-glycan core structures (PubMed:12407114). Contributes to the synthesis of O-linked glycans on mucins and proteoglycans of the central nervous system (PubMed:12407114, PubMed:27629416). Can glycosylate both unmodified peptides and glycopeptides that already contain an O-linked GalNAc sugar. Transfers GalNAc to Thr-/Ser-rich tandem repeats GTTPSPVPTTSTTSAP of MUC5AC. Transfers GalNAc to three consecutive serine/threonine residues on SDC3 forming a triplet-Tn epitope expressed in Purkinje cells of the developing brain (By similarity). May promote neurogenesis through glycosylation and stabilization of PDPN (PubMed:27629416).|||Expressed at high levels in the developing brain, reaching a peak at 17.5 dpc, followed by a decrease at 19.5 dpc. Highly expressed during the postnatal period. Expressed in cortical neural precursor cells at 17.5 dpc.|||Golgi apparatus membrane|||Membrane|||No visible phenotype. It however abolishes Tn antigen in neuronal cells.|||Specifically expressed in neuronal cells. Not expressed in glial cells such as astrocytes. Expressed at low level.|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.|||Was initially wrongly assigned as Galnt8. http://togogenome.org/gene/10090:Tfcp2 ^@ http://purl.uniprot.org/uniprot/Q9ERA0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the grh/CP2 family. CP2 subfamily.|||Binds a variety of cellular promoters including fibrinogen, alpha-globin promoters. Activation of the alpha-globin promoter in erythroid cells is via synergistic interaction with UBP1 (By similarity). Functions as part of the SSP (stage selector protein) complex. Facilitates the interaction of the gamma-globin genes with enhancer elements contained in the locus control region in fetal erythroid cells. Interacts by binding to the stage selector element (SSE) in the proximal gamma-globin promoter (By similarity).|||Binds to DNA as a dimer. Interacts with UBP1 and PIAS1, and is probably part of a complex containing TFCP2, UBP1 and PIAS1. Component of the SSP (stage selector protein) complex, which appears to be a heteromer of TFCP2 and 2 copies of NFE4 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fam43a ^@ http://purl.uniprot.org/uniprot/Q8BUP8 ^@ Similarity ^@ Belongs to the FAM43 family. http://togogenome.org/gene/10090:Dnajb2 ^@ http://purl.uniprot.org/uniprot/Q9QYI5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endoplasmic reticulum membrane|||Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family. In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins. Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes. Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins.|||Interacts with HSP70 (HSPA1A or HSPA1B). Interacts with HSPA8/Hsc70. Interacts with PSMA3 and most probably with the whole proteasomal complex.|||Nucleus|||The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity. The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3. The J domain is required to reduce PRKN cytoplasmic aggregation.|||The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome. The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation. The UIM domains are not required to reduce PRKN cytoplasmic aggregation.|||Ubiquitinated by STUB1; does not lead to proteasomal degradation. http://togogenome.org/gene/10090:Bod1 ^@ http://purl.uniprot.org/uniprot/Q5SQY2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BOD1 family.|||Component of the SET1B complex composed of the catalytic subunit SETD1B, WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1, DPY30 homotrimer and BOD1.|||Required for proper chromosome biorientation through the detection or correction of syntelic attachments in mitotic spindles.|||centrosome|||kinetochore http://togogenome.org/gene/10090:Rem1 ^@ http://purl.uniprot.org/uniprot/O35929 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. RGK family.|||High expression in cardiac muscle. Moderate expression in lung, skeletal muscle and kidney. Low levels in spleen and brain.|||In vitro, interacts with calmodulin in a calcium-dependent manner (By similarity). Interacts 14-3-3 family members including YWHAE, YWHAH, YWHAQ, YWHAZ in a phosphorylation-dependent manner.|||Promotes endothelial cell sprouting and actin cytoskeletal reorganization (By similarity). May be involved in angiogenesis. May function in Ca(2+) signaling.|||Repressed by lipopolysaccharide stimulation. http://togogenome.org/gene/10090:Cdh8 ^@ http://purl.uniprot.org/uniprot/P97291 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.|||Cell membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Psmc4 ^@ http://purl.uniprot.org/uniprot/P54775 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC4 and few additional components. Interacts with NR1I3. Interacts with PAAF1. Interacts with TRIM5. Interacts with ZFAND1 (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC4 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Ube2s ^@ http://purl.uniprot.org/uniprot/Q921J4 ^@ Function|||PTM|||Similarity|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit. Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as an E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination.|||Autoubiquitinated by the APC/C complex during G1, leading to its degradation by the proteasome.|||Belongs to the ubiquitin-conjugating enzyme family.|||Component of the APC/C complex, composed of at least 14 distinct subunits that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa. Within this complex, directly interacts with ANAPC2 and ANAPC4. Interacts with CDC20, FZR1/CDH1 and VHL. http://togogenome.org/gene/10090:Ripply2 ^@ http://purl.uniprot.org/uniprot/Q2WG76 ^@ Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ripply family.|||By MESP2, and acts in a negative feedback loop with MESP2, functioning negatively toward MESP2 to regulate NOTCH signaling in the anterior presomitic mesoderm.|||Expressed in the embryonic anterior presomitic mesoderm. First expressed in S-I at 8.5 dpc, where expression is maintained until 13.5 dpc, with an additional stripe of expression sometimes seen in the rostral part of S0 and S-I.|||Intron retention.|||Nucleus|||Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites.|||The WRPW motif is required for binding to tle/groucho proteins.|||The ripply homology domain is required for transcriptional repression. http://togogenome.org/gene/10090:Tdh ^@ http://purl.uniprot.org/uniprot/Q8K3F7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family.|||Catalyzes the NAD(+)-dependent oxidation of L-threonine to 2-amino-3-ketobutyrate, mediating L-threonine catabolism.|||Homodimer.|||Mitochondrion http://togogenome.org/gene/10090:Vps4a ^@ http://purl.uniprot.org/uniprot/Q8VEJ9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family.|||Highly expressed in testis and moderately in heart and brain. Not detected in spleen, lung, liver, skeletal muscle or kidney.|||Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. It is required for proper accomplishment of various processes including the regulation of endosome size, primary cilium organization, mitotic spindle organization and chromosome segregation, and nuclear envelope sealing and spindle disassembly during anaphase (By similarity). In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Involved in cytokinesis: retained at the midbody by ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is terminated at late cytokinesis. It is then released following dephosphorylation of CHMP4C, leading to abscission. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). Critical for normal erythroblast cytokinesis and correct erythropoiesis (By similarity).|||Late endosome membrane|||Midbody|||Proposed to be monomeric or homodimeric in nucleotide-free form and to oligomerize upon binding to ATP to form two stacked hexameric or heptameric rings with a central pore through which ESCRT-III substrates are translocated in an ATP-dependent manner (By similarity). Interacts with CHMP1A, CHMP1B, CHMP2A, CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C and CHMP6. Interacts with VPS4B; the interaction suggests a heteromeric assembly with VPS4B. Interacts with SPAST. Interacts with IST1. Interacts with ZFYVE19/ANCHR; leading to retain it at midbody (By similarity).|||The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2) (By similarity).|||spindle http://togogenome.org/gene/10090:Gm21245 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Zfp354b ^@ http://purl.uniprot.org/uniprot/Q9QXT9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed at 16.5 dpc in brain, heart, lung, kidney and gut.|||Expressed in brain and kidney. Lower levels in lung, muscle, heart, testis, tongue and eye.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Htr1b ^@ http://purl.uniprot.org/uniprot/P28334|||http://purl.uniprot.org/uniprot/Q0VES5 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A residue in the 7th transmembrane region ('Thr-355' in human, Asn-351 in mouse and rat) is important for species-specific sensitivity to various agonists.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.|||Homodimer. Heterodimer with HTR1D (By similarity).|||Homodimer. Heterodimer with HTR1D.|||Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.|||Membrane|||Mutant male mice display increased aggressivity towards intruders. Treatment with a Htr1b agonist does not trigger increased locomotor behavior in mutant mice, contrary to what is observed with wild-type mice. Treatment with a Htr1b agonist does not inhibit 5-hydroxytryptamine release in the frontal cortex and hippocampus of mutant mice, contrary to what is observed with wild-type mice. Likewise, Htr1b agonists do not inhibit dopamine and acetylcholine release in brains from mutant mice.|||Palmitoylated.|||Phosphorylated.|||Predominantly expressed in striatum and Purkinje cells. http://togogenome.org/gene/10090:Calr4 ^@ http://purl.uniprot.org/uniprot/A2A8Z3|||http://purl.uniprot.org/uniprot/G5CPP0|||http://purl.uniprot.org/uniprot/Q3TQS0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calreticulin family.|||Endoplasmic reticulum lumen http://togogenome.org/gene/10090:Dsg1b ^@ http://purl.uniprot.org/uniprot/B2RQH0|||http://purl.uniprot.org/uniprot/Q7TSF1 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.|||Cytoplasm|||Expressed in embryo at 17 dpc.|||Expressed in epidermis.|||Membrane|||Nucleus|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Blm ^@ http://purl.uniprot.org/uniprot/E9PZ97|||http://purl.uniprot.org/uniprot/O88700 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:9840919). Participates in DNA replication and repair (By similarity). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:9840919). Negatively regulates sister chromatid exchange (SCE) (PubMed:9840919, PubMed:27010503). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution. Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction (By similarity). Recruited by the KHDC3-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks.|||Belongs to the helicase family. RecQ subfamily.|||Binds 1 zinc ion per subunit.|||Highly expressed in testis 12-14 days after birth (corresponding to the pachytene phase) and at much lower levels in brain, heart, liver, lung, thymus, kidney and spleen (PubMed:9840919, PubMed:27010503). Expressed in bone marrow (PubMed:27010503).|||Monomer. Homodimer (via N-terminus). Homotetramer (via N-terminus); dimer of dimers. Homohexamer (via N-terminus). Self-association negatively regulates DNA unwinding amplitude and rate. Oligomer complexes dissociate into monomer in presence of ATP. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with RMI complex. Interacts directly with RMI1 (via N-terminal region) component of RMI complex. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with the KHDC3/FILIA-OOEP/FLOPED scaffold complex and TRIM25 at DNA replication forks (PubMed:29125140). Interacts with ubiquitinated FANCD2 (By similarity). Interacts with SUPV3L1 (By similarity). Interacts with TOP3A (via N-terminal region). Interacts with SPIDR (via C-terminal region); the interaction is direct and required to target BLM to sites of DNA damage.|||Nucleus|||Phosphorylated in response to DNA damage. Phosphorylation requires the FANCA-FANCC-FANCE-FANCF-FANCG protein complex, as well as the presence of RMI1 (By similarity).|||Poly-ubiquitinated by TRIM25 at Lys-264. Deubiquitinated by USP37; leading to stabilization in order to sustain the DNA damage response (By similarity).|||The N-terminal region mediates dimerization and homooligomerization. Both the helicase ATP-binding domain and the helicase C-terminal domain form intramolecular interactions with the HRDC domain in a ATP-dependent manner. The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding. http://togogenome.org/gene/10090:Slc30a1 ^@ http://purl.uniprot.org/uniprot/Q3UM63|||http://purl.uniprot.org/uniprot/Q60738 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Homodimer. Interacts with TMEM163 (By similarity).|||Knockout of Slc30a1 is embryonic lethal.|||Membrane|||Widely expressed.|||Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (Probable). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (PubMed:15451416). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (By similarity). http://togogenome.org/gene/10090:Las1l ^@ http://purl.uniprot.org/uniprot/A2BE28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LAS1 family.|||Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity). Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148.|||Cytoplasm|||Involved in the biogenesis of the 60S ribosomal subunit. Required for maturation of the 28S rRNA (By similarity). Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Stx19 ^@ http://purl.uniprot.org/uniprot/Q8R1Q0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the syntaxin family.|||Cell membrane|||Cytoplasm|||Detected in stomach and skin from embryonic stage 16 (16 dpc) onwards.|||Expressed in stomach, lung and skin (at protein level). In stomach, strongly expressed in the mucosa of the fundus, in epithelial cells of gastric pits, and in gastric glands (at protein level). In skin, expressed in the epidermis, dermis, and epithelial layer of the hair bulb (at protein level).|||Interacts with EGFR.|||Plays a role in endosomal trafficking of the epidermal growth factor receptor (EGFR). http://togogenome.org/gene/10090:Mybpc2 ^@ http://purl.uniprot.org/uniprot/Q5XKE0 ^@ Function|||Similarity ^@ Belongs to the immunoglobulin superfamily. MyBP family.|||Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role (By similarity). http://togogenome.org/gene/10090:Thrap3 ^@ http://purl.uniprot.org/uniprot/Q569Z6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with the large multiprotein complex TRAP (Mediator complex-like). Interacts with SFPQ; the interaction is dependent on SFPQ phosphorylation at 'Thr-687' and inhibits binding of SFPQ to an ESS1 exonic splicing silencer element-containing RNA. Interacts with NXF1. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN. Associated with spliced mRNP complexes. Interacts with HELZ2 and PPARG. Interacts with CLOCK and BMAL1 (By similarity). Component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, KIAA1429, RBM15, BCLAF1 and THRAP3 (By similarity).|||Belongs to the BCLAF1/THRAP3 family.|||Expressed in a circadian manner in the liver with a peak at approximately circadian time (CT) 8 hours (at protein level).|||Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798).|||Nucleus|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Armc1 ^@ http://purl.uniprot.org/uniprot/Q9D7A8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||In association with mitochondrial contact site and cristae organizing system (MICOS) complex components and mitochondrial outer membrane sorting assembly machinery (SAM) complex components may regulate mitochondrial dynamics playing a role in determining mitochondrial length, distribution and motility.|||Interacts with mitochondrial contact site and cristae organizing system (MICOS) complex components IMMT/MIC60 and MICOS10/MIC10 (By similarity). Interacts with mitochondrial outer membrane sorting assembly machinery (SAM) complex components SAMM50 and MTX1 (By similarity).|||Mitochondrion|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Osbpl11 ^@ http://purl.uniprot.org/uniprot/G5E8A0 ^@ Similarity ^@ Belongs to the OSBP family. http://togogenome.org/gene/10090:Lman1l ^@ http://purl.uniprot.org/uniprot/Q8VCD3 ^@ Subcellular Location Annotation ^@ Endoplasmic reticulum-Golgi intermediate compartment membrane http://togogenome.org/gene/10090:Ap5z1 ^@ http://purl.uniprot.org/uniprot/Q3U829 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.|||Cytoplasm|||Nucleus|||Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1. Interacts with ZFYVE26 and SPG11 (By similarity). http://togogenome.org/gene/10090:Kcnq3 ^@ http://purl.uniprot.org/uniprot/Q8K3F6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability. KCNQ2-KCNQ3 channel is selectively permeable to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+). Associates with Na(+)-coupled myo-inositol symporter SLC5A3 forming a coregulatory complex that alters ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation.|||Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.3/KCNQ3 sub-subfamily.|||Cell membrane|||Heterotetramer with KCNQ2; form the heterotetrameric M potassium channel. Interacts with calmodulin; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel. Heteromultimer with KCNQ5. May associate with KCNE2. Interacts with IQCJ-SCHIP1 (PubMed:27979964).|||KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to protein degradation. Degradation induced by NEDD4L is inhibited by USP36.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Pde3a ^@ http://purl.uniprot.org/uniprot/B2RR84|||http://purl.uniprot.org/uniprot/Q9Z0X4 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE3 subfamily.|||Binds 2 divalent metal cations per subunit.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:11420239). Has also activity toward cUMP (By similarity). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (By similarity).|||Inhibited by cGMP.|||Membrane|||cytosol http://togogenome.org/gene/10090:Ebf2 ^@ http://purl.uniprot.org/uniprot/O08792 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the COE family.|||First detected at 9.0 dpc in the first and second archial arches. At 10.0 dpc and 10.5 dpc, expressed in somites, especially the forming sclerotomes. At 12.5 dpc, found in dorsal root ganglia. At 16.5 dpc, expressed in bone-forming areas and adipose tissues, as well as in specific neural tissues. In bone-forming areas, expressed along the mesenchymal condensation at 14.5 dpc, in the perichondrium and in cells invading the cartilagenous structures at 16.5 dpc. In 18.5 dpc tibias, scattered throughout the trabecular/cancellous bone area. In vitro, expression is induced during differentiation of immature osteoblasts, and then declines.|||Forms either a homodimer or a heterodimer with a related family member (PubMed:9151732). Interacts with SIX1 (PubMed:27923061).|||In adult expressed in olfactory epithelium and at a much lower level in Purkinje cells of the cerebellum. In embryo expressed in epithalamus, in cells near the ventricular zone of mesencephalon and on the ventral surface of rhombencephalon, in the developing vomeronasal organ, at a lower level in developing spinal cord. Not expressed in developing retina, inner ear, dorsal root ganglia, trigeminal ganglia and glossopharyngeal ganglia.|||Nucleus|||Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation. Acts in synergy with the Wnt-responsive LEF1/CTNNB1 pathway. Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3'. http://togogenome.org/gene/10090:Il1rn ^@ http://purl.uniprot.org/uniprot/P25085|||http://purl.uniprot.org/uniprot/Q3TBV5|||http://purl.uniprot.org/uniprot/Q542C7|||http://purl.uniprot.org/uniprot/Q542W1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A. Protects from immune dysregulation and uncontrolled systemic inflammation triggered by IL1 for a range of innate stimulatory agents such as pathogens.|||Belongs to the IL-1 family.|||Cytoplasm|||Deficient mice still possess other negative regulators of IL1 activity and adapt to excessive IL1 via shedding of IL1R1.|||Secreted http://togogenome.org/gene/10090:Or52n2c ^@ http://purl.uniprot.org/uniprot/Q8VGW3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppa2 ^@ http://purl.uniprot.org/uniprot/D3Z636|||http://purl.uniprot.org/uniprot/Q91VM9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPase family.|||Homodimer.|||Hydrolyzes inorganic pyrophosphate. This activity is essential for correct regulation of mitochondrial membrane potential, and mitochondrial organization and function.|||Mitochondrion http://togogenome.org/gene/10090:Hinfp ^@ http://purl.uniprot.org/uniprot/Q8K1K9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds MBD2 and a histone deacetylase complex. Interacts with NPAT (By similarity).|||Nucleus|||Transcriptional repressor that binds to the consensus sequence 5'-CGGACGTT-3' and to the RB1 promoter. Transcriptional activator that promotes histone H4 gene transcription at the G1/S phase transition in conjunction with NPAT. Also activates transcription of the ATM and PRKDC genes. Autoregulates its expression by associating with its own promoter.|||Ubiquitinated. Ubiquitination may lead to proteasome-mediated degradation (By similarity). http://togogenome.org/gene/10090:Rsrp1 ^@ http://purl.uniprot.org/uniprot/Q3UC65 ^@ Caution|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RSRP family.|||It is uncertain whether Met-1 or Met-6 is the initiator.|||May be due to intron retention.|||Nucleus|||Phosphorylated. Phosphorylation at Ser-118 and Ser-120 mediates the interaction with spliceosome proteins.|||Probably acts as a spliceosomal factor that contributes to spliceosome assembly and regulates the isoform switching of proteins such as PARP6. http://togogenome.org/gene/10090:Rbbp7 ^@ http://purl.uniprot.org/uniprot/Q60973|||http://purl.uniprot.org/uniprot/Q8C5H3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.|||Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin (By similarity). Subunit of the type B histone acetyltransferase (HAT) complex, composed of RBBP7 and HAT1 (By similarity). Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SUDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex (By similarity). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:27806305). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:27806305). The NuRD complex may interact with MBD3L1. The NuRD complex may interact with MBD3L2 (By similarity). Subunit of the PRC2/EED-EZH2 complex, which is composed of at least EED, EZH2, RBBP4, RBBP7 and SUZ12 (PubMed:20144788). The PRC2/EED-EZH2 complex may also associate with HDAC1. Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1, BPTF, RBBP4 and RBBP7. Within the complex interacts with SMARCA1. Component of the BPFT-SMARCA1 complex at least composed of SMARCA1, BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin. Within the complex interacts with SMARCA1. Interacts with BRCA1. Interacts with CDK2AP1. Interacts with CENPA. Interacts with CHD3. Interacts with CHD4. Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP (By similarity). Interacts with HDAC7 (PubMed:10984530). Interacts with MTA1 (By similarity). Interacts with PWWP2B (PubMed:34180153). Interacts with RB1 (via viral protein-binding domain) (By similarity). Interacts with SUV39H1 (PubMed:11788710).|||Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex (By similarity).|||Higher levels in brain, thymus, lung, spleen, kidney, testis, and ovary/uterus; lower levels in heart, liver, and muscle.|||Nucleus http://togogenome.org/gene/10090:Or10g6 ^@ http://purl.uniprot.org/uniprot/Q8VEU2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dlk1 ^@ http://purl.uniprot.org/uniprot/B4YB46|||http://purl.uniprot.org/uniprot/B4YB48|||http://purl.uniprot.org/uniprot/G3UWU8|||http://purl.uniprot.org/uniprot/Q09163|||http://purl.uniprot.org/uniprot/Q925U3|||http://purl.uniprot.org/uniprot/Q9DAU5 ^@ Caution|||Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expression is elevated in liver after birth but starts to decline around postnatal day 16.|||Highly expressed in fetal liver, placenta, adult adrenal gland, brain, testis and ovary and, to a lesser degree, in adult kidney, muscle, thymus and heart.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May have a role in neuroendocrine differentiation. Inhibits adipocyte differentiation.|||Membrane|||Monomer. Interacts with SH3RF2 (By similarity).|||N- and O-glycosylated. http://togogenome.org/gene/10090:Rnaseh2c ^@ http://purl.uniprot.org/uniprot/Q9CQ18 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase H2 subunit C family.|||Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.|||Nucleus|||The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C. http://togogenome.org/gene/10090:Klk1b16 ^@ http://purl.uniprot.org/uniprot/P04071 ^@ Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily. http://togogenome.org/gene/10090:Lsr ^@ http://purl.uniprot.org/uniprot/Q99KG5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. LISCH7 family.|||Cell membrane|||Death between 12.5 dpc and 15.5 dpc probably due to impaired liver and embryonic development.|||Expressed during embryogenesis (at protein level). Detected from 7.5 dpc to 17 dpc.|||Expressed in eptihelial tissues (at protein level) (PubMed:21245199). Specifically expressed in liver and to a lower extent in kidney (at protein level). Also detected in brain, testis, ovaries, adrenal gland, intestine, muscle, and lung. In colon, only expressed in the lower portion of crypts (PubMed:23239027). Expressed in the liver.|||Expressed in liver, stomach, small intestine and colon. Also detected in other epithelial tissues.|||Homotrimer or homotetramer (By similarity). Assembles into cell-cell contacts (PubMed:21245199). Interacts (via the cytoplasmic domain) with MARVELD2 (via C-terminal cytoplasmic domain); the interaction is required to recruit MARVELD2 to tricellular contacts (PubMed:21245199, PubMed:23239027). Interacts with OCLN (PubMed:23239027).|||Phosphorylation at Ser-308 by MAPK8/JNK1 and MAPK9/JNK2 may be required for exclusive localization at tricellular tight junstions.|||Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (PubMed:15265030). Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (PubMed:21245199, PubMed:23239027).|||tight junction http://togogenome.org/gene/10090:Ier3ip1 ^@ http://purl.uniprot.org/uniprot/Q9CR20 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the YOS1 family.|||Endoplasmic reticulum membrane|||Regulator of endoplasmic reticulum secretion that acts as a key determinant of brain size. Required for secretion of extracellular matrix proteins. Required for correct brain development by depositing sufficient extracellular matrix proteins for tissue integrity and the proliferation of neural progenitors (By similarity). Acts as a regulator of the unfolded protein response (UPR) (PubMed:28915629). http://togogenome.org/gene/10090:Hoxb8 ^@ http://purl.uniprot.org/uniprot/A2A9Z8|||http://purl.uniprot.org/uniprot/P09632 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Antp homeobox family.|||Forms a DNA-binding heterodimer with transcription factor PBX1.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Wnt6 ^@ http://purl.uniprot.org/uniprot/P22727 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Wnt family.|||Detected in ileum, colon and stomach (at protein level).|||Interacts with PORCN.|||Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||extracellular matrix http://togogenome.org/gene/10090:Stard3 ^@ http://purl.uniprot.org/uniprot/Q544C3|||http://purl.uniprot.org/uniprot/Q61542 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STARD3 family.|||Endosome membrane|||Homodimer. Interacts (via the MENTAL domain) with STARD3NL. Interacts (via phosphorylated FFAT motif) with VAPA (via MSP domain). Interacts (via phosphorylated FFAT motif) with VAPB (via MSP domain). Interacts (via phosphorylated FFAT motif) with MOSPD2 (via MSP domain); this interaction allows enrichment of MOSPD2 around endosomes.|||Late endosome membrane|||Membrane|||Phosphorylation at Ser-210 is necessary and sufficient for the direct interaction of the phosphorylated FFAT motif with the MSP domain of MOSPD2, VAPA and VAPB and allows the tethering of two membranes that participates in the formation of ER-endosome contacts. Phosphorylation of the FFAT motif leads to conformation changes. Additional phosphorylations around the core FFAT motif (QFYSPPE) are not essential but strengthen the interaction with MOSPD2, VAPA and VAPB. Phosphorylation at Ser-210 of FFAT motif drives membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB that in turn allows the efficient transport of sterol mediated by the START domain.|||Sterol-binding protein that mediates cholesterol transport from the endoplasmic reticulum to endosomes. The sterol transport mechanism is triggered by phosphorylation of FFAT motif that leads to membrane tethering between the endoplasmic reticulum and late endosomes via interaction with VAPA and VAPB. Acts as a lipid transfer protein that redirects sterol to the endosome at the expense of the cell membrane and favors membrane formation inside endosomes. May also mediate cholesterol transport between other membranes, such as mitochondria membrane or cell membrane. However, such results need additional experimental evidences; probably mainly mediates cholesterol transport from the endoplasmic reticulum to endosomes. Does not activate transcriptional cholesterol sensing. Able to bind other lipids, such as lutein, a xanthophyll carotenoids that form the macular pigment of the retina.|||The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2.|||The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol. It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL.|||The START domain mediates lipid-transfer between membranes. It contains a hydrophobic cavity able to accommodate one lipid molecule, thereby serving as a 'hydrophobic bridge' across the aqueous gap between donor and acceptor organelle membranes. http://togogenome.org/gene/10090:Hddc2 ^@ http://purl.uniprot.org/uniprot/Q3SXD3 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the HDDC2 family.|||Binds 2 divalent metal cations (By similarity). Shows activity with Mn(2+), Co(2+) and Mg(2+) but shows no activity with Zn(2+) (By similarity).|||Catalyzes the dephosphorylation of the nucleoside 5'-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP).|||Homodimer. http://togogenome.org/gene/10090:Pcmtd1 ^@ http://purl.uniprot.org/uniprot/P59913|||http://purl.uniprot.org/uniprot/Q3TGS5 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although the active site residue Ser is conserved, appears to lack catalytic activity in vitro.|||At its N-terminus, contains L-isoaspartate and S-adenosylmethionine (AdoMet) binding motifs. Also contains an extended SOCS box motif, where the Cul-box is separated from the BC-box by ~90 residues, within its C-terminus.|||Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.|||Component of the probable ECS(PCMTD1) E3 ubiquitin-protein ligase complex, at least composed of CUL5, ELOB, ELOC, RBX2 and PCMTD1. Interacts (via the BC-box) with ELOB and ELOC; the interaction is direct and stabilizes PCMTD1.|||Cytoplasm|||Membrane|||Substrate recognition component of an ECS (Elongin BC-CUL5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Specifically binds to the methyltransferase cofactor S-adenosylmethionine (AdoMet) via the N-terminal AdoMet binding motif, but does not display methyltransferase activity. May provide an alternate maintenance pathway for modified proteins by acting as a damage-specific E3 ubiquitin ligase adaptor protein. http://togogenome.org/gene/10090:Rbms2 ^@ http://purl.uniprot.org/uniprot/Q8VC70 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rgs20 ^@ http://purl.uniprot.org/uniprot/Q9QZB1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Fatty acylated. Heavily palmitoylated in the cysteine string motif (By similarity).|||Forms a complex with G(alpha)z/i2 subunits and mu-opioid receptors; the formation of this complex results in mu-opioid receptor desensitization. Interacts with OPRM1 (By similarity).|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G-protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins.|||Membrane|||N- and O-glycosylated in synapsomal membranes.|||Nucleus|||Serine phosphorylated in synapsomal membranes.|||Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation increases binding to the G-proteins, G(alpha)-i2 and G(z), and interaction with mu-opioid receptors. http://togogenome.org/gene/10090:Cops7a ^@ http://purl.uniprot.org/uniprot/Q9CZ04 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CSN7/EIF3M family. CSN7 subfamily.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively (By similarity).|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS5, COPS6 and COPS8. Interacts with PMF1. Interacts with the translation initiation factor EIF3S6. Interacts with CK2 and PKD (By similarity). Interacts directly with ID3 (PubMed:15451666).|||Cytoplasm|||Nucleus|||Phosphorylated by CK2 and PKD kinases. http://togogenome.org/gene/10090:Rtl6 ^@ http://purl.uniprot.org/uniprot/Q505G4 ^@ Developmental Stage|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the LDOC1 family.|||Expressed at 14.5 dpc.|||RTL6 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes.|||Widely expressed. http://togogenome.org/gene/10090:Selenoh ^@ http://purl.uniprot.org/uniprot/Q3UQA7 ^@ Function|||Similarity ^@ Belongs to the SelWTH family.|||May be involved in a redox-related process. http://togogenome.org/gene/10090:Polr2k ^@ http://purl.uniprot.org/uniprot/Q545V5|||http://purl.uniprot.org/uniprot/Q63871|||http://purl.uniprot.org/uniprot/Q8BFX0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo12/eukaryotic RPC10 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively (By similarity).|||Factor that activates expression from a metal response element of the mouse metallothionein-I gene.|||Nucleus http://togogenome.org/gene/10090:Chek2 ^@ http://purl.uniprot.org/uniprot/Q9Z265 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68 (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily.|||Homodimer. Homodimerization is part of the activation process but the dimer may dissociate following activation. Interacts with PML. Interacts with TP53. Interacts with RB1; phosphorylates RB1. Interacts with BRCA1. Interacts (phosphorylated at Thr-68) with MDC1; requires ATM-mediated phosphorylation of CHEK2. Interacts with TP53BP1; modulates CHEK2 phosphorylation at Thr-68 in response to ionizing radiation. Interacts with CDC25A; phosphorylates CDC25A and mediates its degradation in response to ionizing radiation. Interacts with CUL1; mediates CHEK2 ubiquitination and regulation. Interacts with CDKN2AIP. Interacts (via protein kinase domain) with CCAR2 (via N-terminus). Interacts with SIRT1 (By similarity).|||No overt morphological phenotype but apoptosis and cell cycle arrest induced by ionizing radiation are abolished.|||PML body|||Phosphorylated. Phosphorylated at Ser-82 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-77 by ATM and the G2/M transition checkpoint. Phosphorylation at Thr-77 induces homodimerization. Autophosphorylates at Thr-387 and Thr-391 in the T-loop/activation segment upon dimerization to become fully active. DNA damage-induced autophosphorylation at Ser-383 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function. Phosphorylation at Ser-460 also regulates ubiquitination. Phosphorylated by PLK4 (By similarity).|||Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (By similarity).|||Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination (By similarity).|||Ubiquitously expressed with higher levels in the thymus, spleen and colon (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Ccl19 ^@ http://purl.uniprot.org/uniprot/O70460|||http://purl.uniprot.org/uniprot/Q548P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Highly expressed by dendritic cells in mesenteric and peripheral lymph nodes. Significant expression in spleen (T cell zone or periarteriolar lymphatic sheath) and Peyer patches. Low expression in thymus.|||Interacts with TNFAIP6 (via Link domain).|||Secreted|||Strongly chemotactic for naive (L-selectinhi) CD4 T-cells and for CD8 T-cells and weakly attractive for resting B-cells and memory (L-selectinlo) CD4 T-cells. May play a role in promoting encounters between recirculating T-cells and dendritic cells and in the migration of activated B-cells into the T-zone of secondary lymphoid tissues. Binds to chemokine receptor CCR7. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4. http://togogenome.org/gene/10090:Itm2c ^@ http://purl.uniprot.org/uniprot/Q91VK4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ITM2 family.|||Cell membrane|||Interacts with BACE1. Interacts with APP. Interacts with STMN2 (By similarity).|||Lysosome membrane|||Negative regulator of amyloid-beta peptide production. May inhibit the processing of APP by blocking its access to alpha- and beta-secretase. Binding to the beta-secretase-cleaved APP C-terminal fragment is negligible, suggesting that ITM2C is a poor gamma-secretase cleavage inhibitor. May play a role in TNF-induced cell death and neuronal differentiation.|||Type I membrane-bound, as well as soluble, furin has a pre-eminent role in ITM2C proteolytic processing. PCSK7 and PCSK5 may also be involved although to a lesser extent. The soluble form of PCSK7 is incapable of processing ITM2C. Fails to undergo shedding by ADAM10 and intramembrane cleavage by SPPL2B (By similarity). http://togogenome.org/gene/10090:Etv6 ^@ http://purl.uniprot.org/uniprot/P97360|||http://purl.uniprot.org/uniprot/Q80WR3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ETS family.|||Can form homodimers or heterodimers with TEL2 or FLI1. Interacts with L3MBTL1 and HDAC9 (By similarity).|||Nucleus|||Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation. http://togogenome.org/gene/10090:Amotl2 ^@ http://purl.uniprot.org/uniprot/Q8K371 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the angiomotin family.|||Interacts with SRC.|||Phosphorylation at Tyr-107 is necessary for efficient binding to SRC and synergistically functioning with SRC to activate the downstream MAPK pathway.|||Recycling endosome|||Regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Required for proper architecture of actin filaments. Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. Participates in angiogenesis. May play a role in the polarity, proliferation and migration of endothelial cells. Selectively promotes FGF-induced MAPK activation through SRC (By similarity). http://togogenome.org/gene/10090:Dusp12 ^@ http://purl.uniprot.org/uniprot/Q4KL39|||http://purl.uniprot.org/uniprot/Q9D0T2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Dual specificity phosphatase; can dephosphorylate both phosphotyrosine and phosphoserine or phosphothreonine residues. Can dephosphorylate glucokinase (in vitro). Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate and other in vitro substrates.|||Monomer.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Fbxw8 ^@ http://purl.uniprot.org/uniprot/Q8BIA4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Golgi apparatus|||Part of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN. Interacts with OBSL1, CUL1, CUL2, SKP1, CCT6B, PFDN5, CCT2, CCT3, CCT6A, CCT7, VBP1, CCDC8, ARF1, TRIP13, PDCD5 and GORASP1. Interacts with MAP4K1/HPK1 (when autophosphorylated). Associated component of the 3M complex (By similarity). Interacts with CUL7. Interacts with POUF51 (when phosphorylated on 'Ser-347') (PubMed:29153991).|||Reduced embryo size and neonatal lethality. Embryos and placentas are smaller and only a third of the expected number of mice survived birth. Mice that survive remain smaller throughout postnatal development.|||Substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The Cul7-RING(FBXW8) complex mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation. Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions (By similarity).|||Widely expressed. Expressed at higher level in skeletal muscle, cartilage and lung.|||perinuclear region http://togogenome.org/gene/10090:Gprin3 ^@ http://purl.uniprot.org/uniprot/B2RQZ6|||http://purl.uniprot.org/uniprot/Q8BWS5 ^@ Function ^@ May be involved in neurite outgrowth. http://togogenome.org/gene/10090:Afg1l ^@ http://purl.uniprot.org/uniprot/Q3V384 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AFG1 ATPase family.|||Expression is elevated during lactation.|||Found in several complexes of 140-500 kDa. Interacts with YME1L1. Interacts with COX4I1. Interacts with COX5A. Interacts with TP53; mediates mitochondrial translocation of TP53 in response to genotoxic stress such as mitomycin C treatment.|||Highly expressed in heart, kidney, and lactating breast. Present at reduced levels in virgin, pregnant, and involuting breast.|||Mitochondrion membrane|||Putative mitochondrial ATPase. Plays a role in mitochondrial morphology and mitochondrial protein metabolism. Promotes degradation of excess nuclear-encoded complex IV subunits (COX4I1, COX5A and COX6A1) and normal activity of complexes III and IV of the respiratory chain. Mediates mitochondrial translocation of TP53 and its transcription-independent apoptosis in response to genotoxic stress. http://togogenome.org/gene/10090:Paxip1 ^@ http://purl.uniprot.org/uniprot/Q6NZQ4 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expression detected in all tissues examined, including brain stem, cerebellum, cortex, heart, spleen, kidney, liver, thymus and lung.|||Highly expressed in embryonic kidney and brain.|||Interacts with the C-terminal transactivation domain of PAX2 (PubMed:10908331). Forms a constitutive complex with PAGR1 independently of the MLL2/MLL3 complex (PubMed:19124460, PubMed:26744420). Interacts with TP53BP1 (when phosphorylated at the N-terminus by ATM) (By similarity). Interacts with HLTF (By similarity). Component of the KMT2 family MLL2/MLL3 complex (also named ASCOM complex), at least composed of the HMTs KMT2D and/or KMT2C, the common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; required for the association of PAGR1 with the MLL2/MLL3 complex (By similarity). Interacts with NUPR1; this interaction prevents PAXIP1 inhibition of PAX2 transcription factor activity (By similarity).|||Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes such as the MLL2/MLL3 complex. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires Rnf8 and Ube2n. Recruits Tp53bp1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with Tp53bp1 phosphorylated by Atm. Together with Tp53bp1 regulates Atm association (By similarity). Proposed to recruit Pagr1 to sites of DNA damage and the Pagr1:Paxip1 complex is required for cell survival in response to DNA damage independently of the MLL2/MLL3 complex. However, this function has been questioned (PubMed:19124460, PubMed:26744420). Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and Rad51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as Pax2. Associates with gene promoters that are known to be regulated by Kmt2d/Mll2 (By similarity). During immunoglobulin class switching in activated B-cells is involved in trimethylation of histone H3 at 'Lys-4' and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus; this function appears to involve the recruitment of MLL-containing HMT complexes. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex (PubMed:20671152, PubMed:26744420).|||Mice are developmentally retarded, disorganized, and embryonic lethal by 9.5 dpc. Mutant cells appear to replicate DNA but show reduced levels of mitosis and widespread cell death by 8.5 dpc. DNA damage appears to precede nuclear condensation at 7 dpc. Reduced levels of histone H3 methylated at 'Lys-4 in developing tissues.|||Nucleus matrix|||The BRCT 1 and 2 domains mediate the interaction with PAGR1A.|||The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex (PubMed:26744420). The BRCT 5 and 6 domains function as a single module and are necessary and sufficient for in vitro phospho-specific binding (substrates phosphorylated by the kinases ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) in response to gamma irradiation). In contrast, in vivo two pairs of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more efficiently.|||The terminology of MLL proteins in mammalia is not consistent also concerning the terminology of MLL protein-containing complexes. The decribed MLL2/MLL3 complex is commonly described as MLL3/MLL4 complex in literature. http://togogenome.org/gene/10090:Adgre1 ^@ http://purl.uniprot.org/uniprot/Q3U9R0|||http://purl.uniprot.org/uniprot/Q61549 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Deficient mice fail to develop peripheral tolerance after inoculation with antigen because of a lack of efferent regulatory T-cell development.|||In macrophages; but absent from those which are localized within T-cell areas of lymph nodes and spleen. Low level of expression on blood monocytes.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Most adhesion GPCRs proteins undergo autoproteolysis at the GPS domain. ADGRE1 is predicted non-cleavable because of the lack of a consensus catalytic triad sequence within GPS domain.|||Orphan receptor involved in cell adhesion and probably in cell-cell interactions specifically involving cells of the immune system. May play a role in regulatory T-cells (Treg) development. http://togogenome.org/gene/10090:Wwtr1 ^@ http://purl.uniprot.org/uniprot/Q9EPK5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to SLC9A3R2 via the PDZ motif at the plasma membrane (PubMed:11118213). Binds to YWHAZ in vivo and in vitro through the phosphoserine-binding motif RSHSSP (PubMed:11118213). Interacts (via coiled-coil domain) with SMAD2 (via MH1 domain), SMAD3 and SMAD4 (By similarity). Interacts with MED15 (By similarity). Interacts with PAX8 and NKX2-1 (By similarity). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4 (By similarity). Interacts (via WW domain) with PALS1 (PubMed:21145499). Interacts with LATS1 (PubMed:21145499). Interacts with YAP1 (when phosphorylated at 'Ser-112') (PubMed:21145499). Interacts (via WW domain) with PRRG4 (via cytoplasmic domain) (By similarity).|||Binds to transcription factors via its WW domain.|||Cell membrane|||Cytoplasm|||Highly expressed in kidney, heart, placenta and lung.|||Nucleus|||Phosphorylated by LATS2 and STK3/MST2. Phosphorylation by LATS2 results in creation of 14-3-3 binding sites, retention in the cytoplasm, and functional inactivation (By similarity). Phosphorylation results in the inhibition of transcriptional coactivation through YWHAZ-mediated nuclear export.|||The PDZ-binding motif is essential for stimulated gene transcription. It localizes the protein into both punctate nuclear foci and plasma membrane-associated complexes.|||Transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:11118213, PubMed:37215988). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (By similarity). WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation (By similarity). In conjunction with YAP1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (PubMed:21145499). Plays a key role in coupling SMADs to the transcriptional machinery such as the mediator complex (By similarity). Regulates embryonic stem-cell self-renewal, promotes cell proliferation and epithelial-mesenchymal transition (By similarity).|||Ubiquitinated at Lys-46; leading to proteasomal degradation. Deubiquitinated and stabilized by UCHL1 at Lys-46; leading to osteoclastogenesis inhibition. http://togogenome.org/gene/10090:Slc38a2 ^@ http://purl.uniprot.org/uniprot/Q8CFE6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Expressed in cerebral and cerebellar astrocytes and neurons.|||Inhibited by N-methyl-D-glucamine. Inhibited by choline. Allosteric regulation of sodium ions binding by pH.|||Placenta-specific Slc38a2 knockdown reduced fetal weight by 11% at the end of gestation.|||Polyubiquitination by NEDD4L regulates the degradation and the activity of SLC38A2.|||Symporter that cotransports neutral amino acids and sodium ions from the extraccellular to the intracellular side of the cell membrane (PubMed:34406367). The trasnport is pH-sensitive, Li(+)-intolerant, electrogenic, driven by the Na(+) electrochemical gradient and cotransports of neutral amino acids and sodium ions with a stoichiometry of 1:1. May function in the transport of amino acids at the blood-brain barrier (By similarity). May function in the transport of amino acids in the supply of maternal nutrients to the fetus through the placenta (PubMed:16365304). Maintains a key metabolic glutamine/glutamate balance underpinning retrograde signaling by dendritic release of the neurotransmitter glutamate (By similarity). Transports L-proline in differentiating osteoblasts for the efficient synthesis of proline-enriched proteins and provides proline essential for osteoblast differentiation and bone formation during bone development (PubMed:34406367).|||The extracellular C-terminal domain controls the voltage dependence for amino acid transports activity. http://togogenome.org/gene/10090:Nhsl1 ^@ http://purl.uniprot.org/uniprot/Q8CAF4 ^@ Sequence Caution|||Similarity ^@ Belongs to the NHS family.|||Contaminating sequence. Sequence of unknown origin in the C-terminal part.|||Intron retention. http://togogenome.org/gene/10090:Eef1ece2 ^@ http://purl.uniprot.org/uniprot/P0DPD9|||http://purl.uniprot.org/uniprot/P0DPE0|||http://purl.uniprot.org/uniprot/Q80Z57 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Based on a naturally occurring readthrough transcript which produces an Eef1akmt4-Ece2 fusion protein.|||Belongs to the methyltransferase superfamily.|||Binds 1 zinc ion per subunit.|||Converts big endothelin-1 to endothelin-1. May also have methyltransferase activity (By similarity). May play a role in amyloid-beta processing (PubMed:12464614).|||Eef1akmt4-Ece2 and Ece2 double mutant mice are fertile and healthy, and do not display any abnormality in terms of growth or aging.|||Expressed at high levels in central nervous system. Expressed in adrenal glands, ovary and uterus, and at low levels in heart.|||Golgi apparatus membrane|||In the C-terminal section; belongs to the peptidase M13 family.|||In the N-terminal section; belongs to the methyltransferase superfamily.|||Inhibited by phosphoramidon.|||Membrane|||Protein-lysine methyltransferase that efficiently catalyzes three successive methylations on 'Lys-36' in eukaryotic translation elongation factor 1 alpha (EEF1A1 or EEF1A2).|||Weakly expressed in mesenchyme and parts of neural tube at 10.5 dpc. At 13.5 dpc, expressed in anterior part of neural tube, dorsal root ganglia, bilateral sympathetic trunk and heart.|||secretory vesicle membrane http://togogenome.org/gene/10090:Ghrhr ^@ http://purl.uniprot.org/uniprot/P32082 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Little (lit) mice exhibits anterior pituitary hypoplasia.|||Pituitary gland.|||Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion. http://togogenome.org/gene/10090:Prdm13 ^@ http://purl.uniprot.org/uniprot/E9PZZ1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Expressed in the brain, hypothalamus, and embryonic nose and brain tissues.|||Expression is observed in the cerebellum at 12.5-14.5 days post coitum (dpc). Transcripts are detected prominently in the ventricular zone of both the cerebellar vermis and hemispheres.|||May be involved in transcriptional regulation. Is required for the differentiation of Kiss1-expressing neurons in the arcuate (Arc) nucleus of the hypothalamus. Is a critical regulator of GABAergic cell fate in the cerebellum, required for normal postnatal cerebellar development (PubMed:34730112).|||Nucleus http://togogenome.org/gene/10090:Acly ^@ http://purl.uniprot.org/uniprot/Q3V117|||http://purl.uniprot.org/uniprot/Q91V92 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated at Lys-530, Lys-536 and Lys-544 by KAT2B/PCAF (By similarity). Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites (By similarity). Acetylation promotes de novo lipid synthesis (By similarity). Deacetylated by SIRT2 (By similarity).|||Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.|||Homotetramer.|||ISGylated.|||In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.|||In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.|||Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (By similarity). Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation state of Ser-455 (By similarity). Phosphorylation on Ser-455 is decreased by prior phosphorylation on the other 2 residues (By similarity).|||Phosphorylation results in activation of its activity (By similarity). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (By similarity).|||Ubiquitinated at Lys-530, Lys-536 and Lys-544 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation (PubMed:34491895). Ubiquitination is probably inhibited by acetylation at same site (By similarity). BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (PubMed:34491895).|||cytosol http://togogenome.org/gene/10090:Ugt3a1 ^@ http://purl.uniprot.org/uniprot/Q3UP75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||Highly expressed in kidney, while it is expressed at low levels in liver. Not detected in other tissues examined.|||Membrane|||UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity). http://togogenome.org/gene/10090:S100a1 ^@ http://purl.uniprot.org/uniprot/P56565|||http://purl.uniprot.org/uniprot/Q91V77 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Able to bind zinc in vitro; the binding sites are different from the calcium binding sites. The physiological relevance of zinc binding is unclear. Physiological concentrations of potassium antagonize the binding of both divalent cations, especially affecting the high-affinity calcium-binding sites.|||Belongs to the S-100 family.|||Cytoplasm|||Deficient mice show unaltered baseline cardiac function and heart rate, but display deficiencies in their contractile function in response to beta-adrenergic stimulation and enhanced transsarcolemmal Ca(2+) influx (PubMed:11909974). It also significantly accelerates the development of contractile dysfunction after myocardial infarction, with a rapid onset of cardiac remodeling and a transition to heart failure combined with excessive mortality (PubMed:16952982).|||Dimer of either two alpha chains, or two beta chains, or one alpha and one beta chain. Also forms heterodimers with S100P (By similarity). Interacts with AGER (By similarity). Interacts with CAPZA1 (By similarity). Interacts with FKBP4. Interacts with RYR1 and RYR2. Interacts with CACYBP in a calcium-dependent manner. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with ATP2A2 and PLN in a Ca(2+)-dependent manner (By similarity). Interacts with mitochondrial F1-ATPase subunits ATP5F1A and ATP5F1B; these interactions increase F1-ATPase activity (PubMed:17438143).|||Expressed in the cardiac and the skeletal muscles.|||Glutathionylated; glutathionylation increases affinity to calcium about 10-fold.|||Mitochondrion|||Sarcoplasmic reticulum|||Small calcium binding protein that plays important roles in several biological processes such as Ca(2+) homeostasis, chondrocyte biology and cardiomyocyte regulation (PubMed:11909974, PubMed:16952982). In response to an increase in intracellular Ca(2+) levels, binds calcium which triggers conformational changes. These changes allow interactions with specific target proteins and modulate their activity. Regulates a network in cardiomyocytes controlling sarcoplasmic reticulum Ca(2+) cycling and mitochondrial function through interaction with the ryanodine receptors RYR1 and RYR2, sarcoplasmic reticulum Ca(2+)-ATPase/ATP2A2 and mitochondrial F1-ATPase (PubMed:17438143). Facilitates diastolic Ca(2+) dissociation and myofilament mechanics in order to improve relaxation during diastole (By similarity). http://togogenome.org/gene/10090:Trim14 ^@ http://purl.uniprot.org/uniprot/Q8BVW3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Expressed with high level in spleen, thymus, liver and testis. Expressed with low level in the brain, kidney, and skeletal muscle. Expressed in various differentiation stages of B-lymphocytes.|||Interacts with MAVS. Interacts with WRNIP1 and PPP6C; these interactions positively regulate the RIG-I signaling pathway. Interacts with CGAS; this interaction stabilizes CGAS and promotes type I interferon production. Interacts with USP14; this interaction mediates the cleavage of 'Lys-48'-linked ubiquitination of CGAS (By similarity). Interacts with TBK1 (By similarity). Interacts with SPI1 (PubMed:14592421).|||Knockout mice have an impaired herpes simplex virus type 1 (HSV-1)-triggered antiviral responses and become highly susceptible to lethal HSV-1 infection.|||Mitochondrion outer membrane|||Plays a role in the innate immune defense against viruses. Facilitates the type I IFN response by interacting with MAVS at the outer mitochondria membrane and thereby recruiting NF-kappa-B essential modulator IKBKG/NEMO to the MAVS signalosome, leading to the activation of both the IFN regulatory factor 3/IRF3 and NF-kappa-B pathways. Positively regulates the CGAS-induced type I interferon signaling pathway by stabilizing CGAS and inhibiting its autophagic degradation (PubMed:27666593). Inhibits the transcriptional activity of SPI1 in a dose-dependent manner (PubMed:14592421).|||Plays an essential role in the innate immune defense against viruses and bacteria. Facilitates the type I IFN response by interacting with MAVS at the outer mitochondria membrane and thereby recruiting NF-kappa-B essential modulator IKBKG/NEMO to the MAVS signalosome, leading to the activation of both the IFN regulatory factor 3/IRF3 and NF-kappa-B pathways. Positively regulates the CGAS-induced type I interferon signaling pathway by stabilizing CGAS and inhibiting its autophagic degradation (PubMed:27666593). Acts as a scaffold between TBK1 and STAT3 to promote phosphorylation of STAT3 and resolve interferon-stimulated gene (ISG) expression. Inhibits the transcriptional activity of SPI1 in a dose-dependent manner (PubMed:14592421).|||The B-box zinc finger is responsible for inhibition of SPI1-mediated transcriptional activation.|||Ubiquitinated. Undergoes 'Lys-63'-linked polyubiquitination; this modification allows IKBKG/NEMO recruitment to MAVS. Undergoes 'Lys-48'-linked polyubiquitination by RNF125; this modification mediates its degradation via the ubiquitin-proteasome pathway.|||phagosome http://togogenome.org/gene/10090:Stt3a ^@ http://purl.uniprot.org/uniprot/P46978|||http://purl.uniprot.org/uniprot/Q3U573 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STT3 family.|||Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (By similarity). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. This subunit contains the active site and the acceptor peptide and donor lipid-linked oligosaccharide (LLO) binding pockets (By similarity). STT3A is present in the majority of OST complexes and mediates cotranslational N-glycosylation of most sites on target proteins, while STT3B-containing complexes are required for efficient post-translational glycosylation and mediate glycosylation of sites that have been skipped by STT3A (By similarity).|||Component of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (By similarity). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes.|||Despite low primary sequence conservation between eukaryotic catalytic subunits and bacterial and archaeal single subunit OSTs (ssOST), structural comparison revealed several common motifs at spatially equivalent positions, like the DXD motif 1 on the external loop 1 and the DXD motif 2 on the external loop 2 involved in binding of the metal ion cofactor and the carboxamide group of the acceptor asparagine, the conserved Glu residue of the TIXE/SVSE motif on the external loop 5 involved in catalysis, as well as the WWDYG and the DK/MI motifs in the globular domain that define the binding pocket for the +2 Ser/Thr of the acceptor sequon. In bacterial ssOSTs, an Arg residue was found to interact with a negatively charged side chain at the -2 position of the sequon. This Arg is conserved in bacterial enzymes and correlates with an extended sequon requirement (Asp-X-Asn-X-Ser/Thr) for bacterial N-glycosylation.|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Oas1h ^@ http://purl.uniprot.org/uniprot/E9Q326|||http://purl.uniprot.org/uniprot/Q8VI97 ^@ Similarity ^@ Belongs to the 2-5A synthase family. http://togogenome.org/gene/10090:Fabp4 ^@ http://purl.uniprot.org/uniprot/P04117|||http://purl.uniprot.org/uniprot/Q542H7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior.|||Lipid transport protein in adipocytes. Binds both long chain fatty acids and retinoic acid. Delivers long-chain fatty acids and retinoic acid to their cognate receptors in the nucleus.|||Monomer (By similarity). Homodimer. Interacts with PPARG.|||Nucleus http://togogenome.org/gene/10090:Nek4 ^@ http://purl.uniprot.org/uniprot/Q9Z1J2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Cytoplasm|||Expressed ubiquitously among various organs and is up-regulated in the testis.|||Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage (By similarity). Protein kinase that seems to act exclusively upon threonine residues.|||cilium http://togogenome.org/gene/10090:Pou5f1 ^@ http://purl.uniprot.org/uniprot/A0A2I6EDI9|||http://purl.uniprot.org/uniprot/P20263 ^@ Biotechnology|||Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family.|||Belongs to the POU transcription factor family. Class-5 subfamily.|||Cytoplasm|||Down-regulated during differentiation to endoderm and mesoderm.|||ERK1/2-mediated phosphorylation at Ser-106 promotes nuclear exclusion and proteasomal degradation. Phosphorylation at Thr-228 and Ser-229 decrease DNA-binding and alters ability to activate transcription (By similarity). JNK1/2-mediated phosphorylation at Ser-347 promotes proteasomal degradation (PubMed:29153991).|||Expressed the totipotent and pluripotent stem cells of the pregastrulation embryo. Also expressed in primordial germ cells and in the female germ line. Absent from adult tissues.|||Interacts with PKM. Interacts with WWP2 (By similarity). Interacts with UBE2I and ZSCAN10 (PubMed:17496161, PubMed:19740739). Interacts with PCGF1 (By similarity). Interacts with ESRRB; recruits ESRRB near the POU5F1-SOX2 element in the NANOG proximal promoter; the interaction is DNA independent (PubMed:18662995). Interacts with ZNF322 (PubMed:24550733). Interacts with MAPK8 and MAPK9; the interaction allows MAPK8 and MAPK9 to phosphorylate POU5F1 on Ser-347 (PubMed:29153991). Interacts (when phosphorylated on Ser-347) with FBXW8 (PubMed:29153991). Interacts with FBXW4 (PubMed:29153991). Interacts with SOX2 and SOX15; binds synergistically with either SOX2 or SOX15 to DNA (PubMed:15863505). Interacts with DDX56 (PubMed:32703285).|||Nucleus|||POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.|||Repressed by retinoic acid (RA).|||Sumoylation enhances the protein stability, DNA binding and transactivation activity. Sumoylation is required for enhanced YES1 expression.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||The POU-specific domain mediates interaction with PKM.|||Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') (PubMed:1972777, PubMed:1690859, PubMed:1967980, PubMed:17525163, PubMed:23376973). Forms a trimeric complex with SOX2 or SOX15 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (PubMed:15863505, PubMed:17097055, PubMed:17496161, PubMed:19740739). Critical for early embryogenesis and for embryonic stem cell pluripotency (PubMed:1972777, PubMed:1690859, PubMed:17496161, PubMed:18662995, PubMed:19740739, PubMed:29153991, PubMed:23376973, PubMed:32703285).|||Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination by WWP2 leading to proteasomal degradation. http://togogenome.org/gene/10090:Pou2f2 ^@ http://purl.uniprot.org/uniprot/Q00196 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates octamer-containing promoters.|||Belongs to the POU transcription factor family. Class-2 subfamily.|||Cytoplasm|||Either absent in, or expressed at very low levels in neuronal cells and brain.|||Expressed at higher levels in B-cells than in neuronal cells.|||Expressed at lower levels in neuronal cells than in B cells.|||Expressed in all tissues tested: mammary gland, liver, spleen, lung, kidney intestine, uterus and ovary of a virgin mouse. Levels of isoform OCT2.7 are highest in spleen and lung. In mammary gland, expression is localized to the alveolus epithelial cells.|||Expressed in neuronal cell lines and brain, but not dorsal root ganglia.|||Expressed in neuronal cell lines, and at lower levels in neuroblastoma and dorsal root ganglia.|||Highest in B cells, but also present in brain (neuronal and glial cells), intestine, kidney, and testes.|||In B cells, expression is highly increased upon activation by LPS or CpG.|||Interacts with NR3C1, AR and PGR. Interacts with POU2AF1; the interaction increases POU2F2 transactivation activity.|||Mutants show normal development of germinal center B cells when infected by influenza virus.|||Nucleus|||Represses some promoters and activate others (PubMed:1281152, PubMed:2011512). Activates the U2 small nuclear RNA (snRNA) promoter (By similarity).|||Represses some promoters and activate others.|||The isoform OCT2b described in PubMed:7888080 corresponds to the isoform OCT2a of PubMed:1976089. To avoid any confusion, we use the nomenclature from PubMed:2011512 to describe the different isoforms.|||Transactivation activity is enhanced by transcriptional coactivator POU2AF1.|||Transcription factor that specifically binds to the octamer motif (5'-ATTTGCAT-3') (PubMed:2011512, PubMed:1281152). Regulates IL6 expression in B cells with POU2AF1 (PubMed:23045607). Regulates transcription in a number of tissues in addition to activating immunoglobulin gene expression. Modulates transcription transactivation by NR3C1, AR and PGR.|||Unable to bind to the octamer motif, but can still activate the beta-casein gene promoter at low levels.|||Widely but not homogeneously expressed in developing nervous system. Expression levels in mammary glands are barely detectable in virgin mice, levels increase during pregnancy, reaching a maximum during late pregnancy, then decrease during lactation becoming very low post-lactation.|||Widely expressed in the developing nervous system but expression is confined to very specific regions in the adult brain, it is expressed at a lower level in B cells. http://togogenome.org/gene/10090:Il7r ^@ http://purl.uniprot.org/uniprot/P16872|||http://purl.uniprot.org/uniprot/Q5FW78|||http://purl.uniprot.org/uniprot/Q8C9W4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||Membrane|||N-glycosylated IL-7Ralpha binds IL7 300-fold more tightly than the unglycosylated form.|||Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).|||Spleen, thymus and fetal liver.|||The IL7 receptor is a heterodimer of IL7R and IL2RG. The TSLP receptor is a heterodimer of CRLF2 and IL7R.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Rbms3 ^@ http://purl.uniprot.org/uniprot/Q8BWL5 ^@ Function|||Subcellular Location Annotation ^@ Binds poly(A) and poly(U) oligoribonucleotides.|||Cytoplasm http://togogenome.org/gene/10090:Vmn2r69 ^@ http://purl.uniprot.org/uniprot/G3XA45 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Chst14 ^@ http://purl.uniprot.org/uniprot/Q80V53 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 2 family.|||Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of dermatan sulfate. Plays a pivotal role in the formation of 4-0-sulfated IdoA blocks in dermatan sulfate. Transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is substituted with an alpha-linked iduronic acid (IdoUA) at the C-3 hydroxyl. Transfers sulfate more efficiently to GalNAc residues in -IdoUA-GalNAc-IdoUA- than in -GlcUA-GalNAc-GlcUA-sequences. Has preference for partially desulfated dermatan sulfate. Addition of sulfate to GalNAc may occur immediately after epimerization of GlcUA to IdoUA. Appears to have an important role in the formation of the cerebellar neural network during postnatal brain development.|||Golgi apparatus membrane|||Low levels of expression in olfactory bulb, caudate putamen, cerebral cortex, hippocampus, thalamus, midbrain and cerebellum during early postnatal development. In later stages, exclusively expressed in cerebellum culminating at P14 of postnatal development. http://togogenome.org/gene/10090:Dennd2a ^@ http://purl.uniprot.org/uniprot/Q8C4S8 ^@ Function|||Subcellular Location Annotation ^@ Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. May play a role in late endosomes back to trans-Golgi network/TGN transport (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Bmx ^@ http://purl.uniprot.org/uniprot/B1AUL6|||http://purl.uniprot.org/uniprot/P97504 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Interacts with BCAR1, CAV1, MYD88, PTK2/FAK1, RUFY1, RUFY2, STAT3, TIRAP and TNFRSF1B.|||Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells.|||Phosphorylated in response to protein I/II and to LPS. Phosphorylation at Tyr-542 by SRC and by autocatalysis leads to activation and is required for STAT3 phosphorylation by BMX.|||SH2 domain mediates interaction with RUFY1.|||Specifically expressed in the endocardium of the developing heart as well as in the endocardium of the left ventricle and in the endothelium of large arteries in adult mice.|||TEK and vascular endothelial growth factor receptor 1 (FLT1) stimulate BMX tyrosine kinase activity. Activated by integrins through the mediation of PTK2/FAK1 (By similarity). Activated by TNF through the mediation of TNFRSF1B (By similarity). http://togogenome.org/gene/10090:Tnfaip3 ^@ http://purl.uniprot.org/uniprot/Q3TBB9|||http://purl.uniprot.org/uniprot/Q60769|||http://purl.uniprot.org/uniprot/Q7TQD1 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C64 family.|||By cytokines. TNF-alpha may regulate expression in the thymus. Up-regulated in presence of reactive oxygen species (ROS), like H(2)O(2), in LPS-tolerized macrophages.|||Cytoplasm|||Found in most tissues during development. Strikingly high levels are found in lymphoid organs, including the thymus, spleen, and gut-associated lymphoid tissue. Constitutively expressed in immature and mature thymocyte subpopulations as well as in resting peripheral T-cells; activation of these leads to down-regulation.|||Homodimer. Interacts with TNIP1, TAX1BP1 and TRAF2. Interacts with RNF11, ITCH and TAX1BP1 only after TNF stimulation; these interaction are transient and they are lost after 1 hour of stimulation with TNF (By similarity). Interacts with YWHAZ and YWHAH. Interacts with IKBKG; the interaction is induced by TNF stimulation and by polyubiquitin. Interacts with RIPK1. Interacts with UBE2N; the interaction requires TAX1BP1. Interacts with TRAF6 (By similarity).|||Lysosome|||Nucleus|||The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes 'Lys-63'-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin (By similarity).|||The OTU domain mediates the deubiquitinase activity.|||Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages. http://togogenome.org/gene/10090:Cisd3 ^@ http://purl.uniprot.org/uniprot/B1AR13 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CISD protein family.|||Binds 2 [2Fe-2S] clusters per subunit.|||Can transfer its iron-sulfur clusters to the apoferrodoxins FDX1 and FDX2. Contributes to mitochondrial iron homeostasis and in maintaining normal levels of free iron and reactive oxygen species, and thereby contributes to normal mitochondrial function.|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Tppp2 ^@ http://purl.uniprot.org/uniprot/Q0P5Y3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TPPP family.|||Male subfertility with a significantly decreased sperm count and motility (PubMed:30680919). Sperm shows increased irregular mitochondria lacking lamellar cristae, abnormal expression of electron transfer chain molecules, lower ATP levels, decreased mitochondrial membrane potential and increased apoptotic index (PubMed:30680919).|||Only expressed in male reproductive organs, including testis (PubMed:30680919). Expressed in elongating spermatids at stages IV-VIII of the seminiferous epithelial cycle in testis and in mature sperm in the epididymis (PubMed:30680919).|||Probable regulator of microtubule dynamics required for sperm motility (Probable). In contrast to other members of the family, has no microtubule bundling activity (By similarity).|||cytosol|||flagellum http://togogenome.org/gene/10090:Slc26a3 ^@ http://purl.uniprot.org/uniprot/Q9WVC8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Cell membrane|||Expressed in spermatogenic cells (PubMed:21976599). Expressed at high levels in cecum and colon and at lower levels in small intestine (PubMed:10428871).|||Interacts with PDZK1 (By similarity). Interacts with CFTR, SLC26A6 and NHERF1 (PubMed:21976599). Interacts (via PDZ-binding motif) with NHERF4 (via the third PDZ domain) (PubMed:22627094). This interaction leads to decreased expression of SLC26A3 on the cell membrane resulting in its reduced exchanger activity (By similarity).|||Mediates chloride-bicarbonate exchange with a chloride bicarbonate stoichiometry of 2:1 in the intestinal epithelia (PubMed:10428871). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:21976599).|||Membrane|||N-glycosylation is required for efficient cell surface expression, and protection from proteolytic degradation. http://togogenome.org/gene/10090:Napsa ^@ http://purl.uniprot.org/uniprot/O09043|||http://purl.uniprot.org/uniprot/Q3U7H1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase A1 family.|||Expressed at the highest levels in the kidney, at a moderate level in the lung, and at low levels in the spleen and adipose tissue.|||May be involved in processing of pneumocyte surfactant precursors.|||Secreted http://togogenome.org/gene/10090:Neurl1b ^@ http://purl.uniprot.org/uniprot/Q0MW30 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase involved in regulation of the Notch pathway through influencing the stability and activity of several Notch ligands.|||Expressed in the limb buds and dorsal root ganglia. Expressed in brain and kidney and at low levels in the heart.|||Interacts with DLL1 and DLL4. http://togogenome.org/gene/10090:Tfr2 ^@ http://purl.uniprot.org/uniprot/Q9JKX3 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M28 family. M28B subfamily.|||Cell membrane|||Cytoplasm|||Down-regulated during erythrocyte differentiation. Expression unchanged by cellular iron status.|||First expressed between embryo days 8 and 11. In the liver, expression increases during development from embryo day 13 to adulthood while, in the spleen, levels remain constant throughout development.|||Lacks most of the extracellular domain.|||Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation.|||Predominantly expressed in liver. Also expressed in kidney, spleen, brain, lung, heart and muscle with very low expression in kidney, muscle and heart. http://togogenome.org/gene/10090:Fam243 ^@ http://purl.uniprot.org/uniprot/Q8CDS7 ^@ Similarity ^@ Belongs to the FAM243 family. http://togogenome.org/gene/10090:BC051665 ^@ http://purl.uniprot.org/uniprot/E9Q623|||http://purl.uniprot.org/uniprot/Q3ULD9|||http://purl.uniprot.org/uniprot/Q80X23 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C1 family.|||Lysosome http://togogenome.org/gene/10090:Zyg11b ^@ http://purl.uniprot.org/uniprot/Q3UFS0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the zyg-11 family.|||Interacts with ELOC/Elongin C. Part of an E3 ubiquitin ligase complex including ZYG11B, CUL2 and Elongin BC.|||Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC. Acts redudantly with ZER1 to target substrates bearing N-terminal glycine degrons for proteasomal degradation. Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N-terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N-myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation. http://togogenome.org/gene/10090:Hdac1 ^@ http://purl.uniprot.org/uniprot/O09106|||http://purl.uniprot.org/uniprot/Q58E49 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the histone deacetylase family. HD Type 1 subfamily.|||Belongs to the histone deacetylase family. HD type 1 subfamily.|||By interleukin-2.|||Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10615135, PubMed:15542849, PubMed:21960634, PubMed:30279482). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:10615135, PubMed:15542849, PubMed:21960634). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:10615135, PubMed:21960634). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity). Also functions as deacetylase for non-histone targets, such as NR1D2, RELA, SP1, SP3 and TSHZ3 (By similarity). Deacetylates SP proteins, SP1 and SP3, and regulates their function (By similarity). Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons (By similarity). Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation (By similarity). Deacetylates TSHZ3 and regulates its transcriptional repressor activity (By similarity). Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B (By similarity). Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity (By similarity). Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:17707228). Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer (PubMed:15226430, PubMed:24736997). Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation (PubMed:15226430). In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones (PubMed:30279482).|||Nucleus|||Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7, the core complex associates with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex (PubMed:11909966, PubMed:9702189). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:27806305). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:27806305). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80 (By similarity). The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (By similarity). Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2 (By similarity). Found in a trimeric complex with APBB1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (By similarity). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC2 (By similarity). Component of a RCOR/GFI/KDM1A/HDAC complex (PubMed:17707228). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 (By similarity). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2 (By similarity). The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A (PubMed:24413057). Associates with the 9-1-1 complex; interacts with HUS1 (By similarity). Found in a complex with DNMT3A and HDAC7 (PubMed:10984530, PubMed:12616525). Found in a complex with YY1, SIN3A and GON4L (PubMed:21454521). Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain (By similarity). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (PubMed:28554894). Interacts with GFI1; the interaction is direct (PubMed:17707228). Interacts directly with GFI1B (PubMed:17707228). Interacts with TSHZ3 (via N-terminus); the interaction is direct (By similarity). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (By similarity). Interacts with BANP (PubMed:16166625). Interacts with BAZ2A/TIP5 (PubMed:12198165, PubMed:16085498). Interacts with BCL6 (By similarity). Interacts with BCOR (By similarity). Interacts with BHLHE40/DEC1 (By similarity). Interacts with BRCC3; this interaction is enhanced in the presence of PWWP2B (PubMed:34180153). Interacts with BRMS1 (By similarity). Interacts with BRMS1L (By similarity). Interacts with C10orf90/FATS (via its N-terminal); the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21 (PubMed:20154723). Interacts with CBFA2T3 (PubMed:11533236). Interacts with CCAR2 (By similarity). Interacts with CDK2AP1 (By similarity). Interacts with CHD3 (By similarity). Interacts with CHD4 (By similarity). Interacts with CHFR (By similarity). Interacts with CIART (PubMed:24736997). Interacts with CDKN1A/p21 (PubMed:20154723). Interacts with CDK5 complexed to CDK5R1 (p25) (PubMed:20154723). Interacts with CRY1 (PubMed:15226430). Interacts with DAXX (By similarity). Interacts with DDIT3/CHOP (PubMed:22242125). Interacts with DDX5 (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with DNMT1 (PubMed:10615135). Interacts with DNTTIP1 (By similarity). Interacts with E4F1 (By similarity). Interacts with EP300 (By similarity). Interacts with ERCC6 (By similarity). Interacts with GATAD2A (By similarity). Interacts with HCFC1 (By similarity). Interacts with HDAC9 (PubMed:11022042, PubMed:15711539, PubMed:16611996). Interacts with HUS1 (By similarity). Interacts with INSM1 (PubMed:24227653). Interacts with KDM4A (By similarity). Interacts with KDM5A; this interaction impairs histone deacetylation (PubMed:21960634). Interacts with KDM5B (By similarity). Interacts with KLF1 (PubMed:15542849). Interacts with MBD3L2 (By similarity). Interacts with MIER1 (By similarity). Interacts with NFE4 (By similarity). Interacts with NR4A2/NURR1 (PubMed:19144721). Interacts with NR1D2 (via C-terminus) (By similarity). Interacts with NRIP1 (PubMed:15060175). Interacts with NSD2 (PubMed:19483677). Interacts with PACS2 (By similarity). Interacts with PHB2 (PubMed:15140878). Interacts with PPHLN1 (By similarity). Interacts with PRDM6 (PubMed:16537907). Interacts with PRDM16 (By similarity). Interacts with PWWP2A in a MTA1-dependent manner (PubMed:30228260). Interacts with PWWP2B (PubMed:30228260, PubMed:34180153). Interacts with RB1 (By similarity). Interacts with RERE (PubMed:14645126). Interacts with SANBR (via the BTB domain) (PubMed:33831416). Interacts with SAMSN1 (PubMed:20478393). Interacts with SAP30L (By similarity). Interacts with SETDB1 (PubMed:12398767). Interacts with SIN3A (By similarity). Interacts with SMAD3 (By similarity). Interacts with SMAD4; positively regulated by ZBTB7A (By similarity). Interacts with SMARCAD1 (By similarity). Interacts with SMARCA4/BRG1 (By similarity). Interacts with SMYD2 (PubMed:16805913). Interacts with SMYD4 (via MYND-type zinc finger) (By similarity). Interacts with SP1; the interaction deacetylates SP1 and regulates its transcriptional activity (By similarity). Interacts with SP3; the interaction deacetylates SP3 and regulates its transcriptional activity (By similarity). In vitro, C(18) ceramides increase this interaction and the subsequent SP3 deacetylation and SP3-mediated repression of the TERT promoter (By similarity). Interacts with SPEN/MINT (By similarity). Interacts with SPHK2 (By similarity). Interacts with SUV39H1 (PubMed:11788710). Interacts with TGIF (By similarity). Interacts with TGIF2 (By similarity). Interacts with TRAF6 (By similarity). Interacts with TRIM28; the interaction recruits HDAC1 to E2F1 and inhibits its acetylation (By similarity). Interacts with TSC22D3 isoform 1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity (PubMed:20124407). Interacts with UHRF1 (By similarity). Interacts with UHRF2 (By similarity). Interacts with ZBTB7A (By similarity). Interacts with ZMYND8 (By similarity). Interacts with ZMYND15 (PubMed:20675388). Interacts with ZNF431 (PubMed:21177534). Interacts with ZNF516; this interaction is enhanced in the presence of PWWP2B (PubMed:34180153). Interacts with ZNF541 (PubMed:18849567). Interacts with ZNF638 (By similarity). Interacts with ZNHIT1 (PubMed:19501046). Interacts with the non-histone region of MACROH2A1 (PubMed:16107708). Identified in a complex with HDAC2, KCTD19, DNTTIP1 and ZNF541 (PubMed:34075040, PubMed:35341968). Interacts with MSX3 (PubMed:11115394).|||Phosphorylation on Ser-421 and Ser-423 promotes enzymatic activity and interactions with NuRD and SIN3 complexes. Phosphorylated by CDK5.|||Sumoylated on Lys-444 and Lys-476; which promotes enzymatic activity. Desumoylated by SENP1.|||Ubiquitinated by CHFR and KCTD11, leading to its degradation by the proteasome.|||Widely expressed with higher levels in thymus and testis and lower levels in liver. Present in muscle (at protein level). http://togogenome.org/gene/10090:Rabep2 ^@ http://purl.uniprot.org/uniprot/Q91WG2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the rabaptin family.|||Cytoplasm|||Early endosome|||Heterodimer with RABGEF1. The dimer binds RAB5A that has been activated by GTP-binding. Interacts with SDCCAG8; this interaction is important for ciliogenesis regulation. Interacts with RAB4A; this interaction may mediate VEGFR2 cell surface expression.|||Plays a role in membrane trafficking and in homotypic early endosome fusion. Participates in arteriogenesis by regulating vascular endothelial growth factor receptor 2/VEGFR2 cell surface expression and endosomal trafficking. By interacting with SDCCAG8, localizes to centrosomes and plays a critical role in ciliogenesis.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Mon1b ^@ http://purl.uniprot.org/uniprot/Q8BMQ8 ^@ Similarity|||Subunit ^@ Belongs to the MON1/SAND family.|||Interacts with CCNT2; down-regulates CCNT2-mediated activation of viral promoters during herpes simplex virus 1/HHV-1 infection. Found in a complex with RMC1, CCZ1 MON1A and MON1B. http://togogenome.org/gene/10090:Krtap5-4 ^@ http://purl.uniprot.org/uniprot/Q62220 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 5 family.|||Expressed during the active phases of the hair cycle in the medulla and the inner root sheath of the forming hair. Also expressed in the upper layers of the epidermis of skin.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Zfp462 ^@ http://purl.uniprot.org/uniprot/B1AWL2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected at 6.5 days post coitum (dpc) in the developing central nervous system (PubMed:17207666). At 7.75 dpc, expression is limited to the headfolds (PubMed:17207666). At 8 dpc, transcripts are detected in the midline neural groove (PubMed:17207666). Between 8 dpc and 9.5 dpc, it is found in the developing forebrain, brainstem, spinal cord, branchial arches, otic vesicles, midbrain and hindbrain folds (PubMed:17207666, PubMed:17353115). At 10.5 dpc, expression is detected in the telencephalic vesicles, branchial arches, otic vesicles, dorsal root ganglia, somites, spinal cord and forelimb buds, specifically in migratory muscle progenitor cells (PubMed:17207666). At 11.5 dpc, it is detected in telencephalic vesicles, midbrain-hindbrain boundary, the spinal cord, branchial arches, dorsal root ganglia, fore- and hindlimb buds and somites (PubMed:17207666, PubMed:17353115). Also detected at 11.5 dpc throughout the wall of the telencephalic vesicle and the medial and lateral ganglionic eminence (PubMed:17353115). At 14.5 dpc, expression is detected in the entire cerebral cortex, with higher levels in the developing hippocampus and septal area (PubMed:17207666). Expression becomes more graded by 16.5 and 18.5 dpc, where it is detected in the caudal and medial cerebral cortex, hippocampus and retrosplenial cortex (PubMed:17207666). Detected at 16.5 dpc in female genital tract (PubMed:17353115). It is also detected in the olfactory bud at 18.5 dpc (PubMed:17207666). Detected at 9.5 dpc in embryos (PubMed:20219459). Detected from 7.5 dpc in the brain, with highest levels of expression being detected at postnatal day 1 (PubMed:27621227). Expression remains at high levels at postnatal day 7 and begins to decrease by postnatal day 14 (PubMed:27621227). Expression is decreased further by postnatal day 30 (PubMed:27621227).|||Embryonic lethal (PubMed:27621227). Knockout mice do not develop past 18.5 days post coitum and exhibit smaller sized eyes with neural-tube defects (PubMed:27621227). Heterozygous mice exhibit decreased expression and delayed development (PubMed:27621227). Heterozygous mice grow slower, weigh less than wild-type mice and have significantly reduced brain weight (PubMed:27621227). They also exhibit lowered levels of PBX1 and HOXB8 (PubMed:27621227). Mice also exhibit anxiety-like behaviors with excessive grooming, resulting in gradual hair loss (PubMed:27621227).|||Expressed in the cerebral cortex (at protein level) (PubMed:17207666, PubMed:27621227). Expressed in embryonic stem cells (at protein level) (PubMed:20219459). Expressed in heart, liver, kidney, muscle, and female and male genital tracts (at protein level) (PubMed:27621227, PubMed:17353115).|||Interacts with PBX1 isoform PBX1b; this interaction prevents PBX1-HOXA9 heterodimer from forming and binding to DNA.|||Nucleus|||Zinc finger nuclear factor involved in transcription by regulating chromatin structure and organization (PubMed:20219459, PubMed:21570965). Involved in the pluripotency and differentiation of embryonic stem cells by regulating SOX2, POU5F1/OCT4, and NANOG (PubMed:21570965). By binding PBX1, prevents the heterodimerization of PBX1 and HOXA9 and their binding to DNA (PubMed:17353115). Regulates neuronal development and neural cell differentiation (PubMed:21570965, PubMed:27621227). http://togogenome.org/gene/10090:Mmp14 ^@ http://purl.uniprot.org/uniprot/P53690 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (PubMed:10520996). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (By similarity). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues (By similarity). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (By similarity).|||Highly expressed in placenta, kidney, heart, lung, embryonic skeletal and periskeletal tissues.|||Interacts (via C-terminal cytoplasmic tail) with BST2. Interacts with DLL1; inhibits DLL1-induced Notch signaling.|||Melanosome|||Membrane|||Not detected before day 10.5. At day 12.5, prominently expressed in large arteries and the umbilical arteries, expressed at lower levels in the myocardium, craniofacial mesenchyme, nasal epithelium and liver capsule. At days 14.5 and 17.5, expressed in the musculoskeletal system, and ossification areas, with continued expression in the arterial tunica media.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||Tyrosine phosphorylated by PKDCC/VLK. http://togogenome.org/gene/10090:Gtpbp3 ^@ http://purl.uniprot.org/uniprot/B2RRS4|||http://purl.uniprot.org/uniprot/Q923K4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. TrmE GTPase family.|||GTPase involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.|||Mitochondrion|||Ubiquitously expressed. Highly expressed in tissues with high metabolic rates including heart, liver and brain. Weakly expressed in skeletal muscle. http://togogenome.org/gene/10090:Txnl4a ^@ http://purl.uniprot.org/uniprot/P83877|||http://purl.uniprot.org/uniprot/Q78JM7|||http://purl.uniprot.org/uniprot/Q9CQX6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DIM1 family.|||Belongs to the acetyltransferase family. ARD1 subfamily.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U5 snRNP complex. Component of the U4/U6-U5 tri-snRNP complex. The U4/U6-U5 tri-snRNP complex is a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Directly interacts with CD2BP2. Interacts with HNRPF, HNRPH2, NEDD9 and PQBP1. Interacts with ERBB4.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes that are involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). http://togogenome.org/gene/10090:Npvf ^@ http://purl.uniprot.org/uniprot/Q3UUP8|||http://purl.uniprot.org/uniprot/Q9ESQ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FARP (FMRFamide related peptide) family.|||Neuropeptide RFRP-1 acts as a potent negative regulator of gonadotropin synthesis and secretion. Neuropeptides NPSF and NPVF efficiently inhibit forskolin-induced production of cAMP. Neuropeptide NPVF blocks morphine-induced analgesia (By similarity).|||Secreted http://togogenome.org/gene/10090:Asb3 ^@ http://purl.uniprot.org/uniprot/Q9WV72 ^@ Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Interacts with ELOB and TNFRSF1B.|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes TNFRSF1B (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes.|||Widely expressed; highest expression in testis and spleen. http://togogenome.org/gene/10090:Spata4 ^@ http://purl.uniprot.org/uniprot/Q8K3V1 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ May play a role in apoptosis regulation.|||Nucleus|||Testis. http://togogenome.org/gene/10090:Spaca7 ^@ http://purl.uniprot.org/uniprot/Q9D2S4 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Involved in fertilization. Seems not to play a direct role in sperm-egg binding or gamete fusion.|||Secreted|||Testis-specific (PubMed:22495889, PubMed:24307706). Expressed in zygotene and pachytene spermatocytes, round spermatids, elongating spermatids and spermatozoa (at protein level) (PubMed:22495889, PubMed:24307706). Testis-specific (PubMed:22495889).|||acrosome lumen http://togogenome.org/gene/10090:Vmn1r6 ^@ http://purl.uniprot.org/uniprot/Q8R2D4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Glod4 ^@ http://purl.uniprot.org/uniprot/Q9CPV4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glyoxalase I family.|||Interacts with NUDT9.|||Mitochondrion http://togogenome.org/gene/10090:Prkg1 ^@ http://purl.uniprot.org/uniprot/P0C605|||http://purl.uniprot.org/uniprot/Q8BND1 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 65 kDa monomer is produced by proteolytic cleavage.|||Autophosphorylation increases kinase activity.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.|||Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity (By similarity).|||Cytoplasm|||Detected in cerebellum, hippocampus, dorsomedial hypothalamus, medulla, subcommissural organ, cerebral cortex, amygdala, habenulae, various hypothalamic regions, olfactory bulb, pituitary gland, and retina. Isoform alpha is prominent in the cerebellum and medulla, whereas isoform Beta is predominant in the cortex, hippocampus, hypothalamus, and olfactory bulb.|||Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.|||In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.|||Isoform alpha: parallel homodimer or heterodimer and also heterotetramer. Interacts directly with PPP1R12A. Non-covalent dimer of dimer of PRKG1-PRKG1 and PPP1R12A-PPP1R12A. This interaction targets PRKG1 to stress fibers to mediate smooth muscle cell relaxation and vasodilation in responses to rises in cGMP (By similarity). Isoform beta: antiparallel homodimer. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1 (By similarity). Interacts with IRAG1. Forms a stable complex with ITPR1, IRAG1, and isoform beta of PRKG1 (By similarity). Interacts with TRPC7 (via ankyrin repeat domain) (By similarity). Isoform alpha interacts with RGS2 (By similarity). Interacts with GTF2I (By similarity).|||Leads to premature death at approximately 6 weeks of age, presumably due to smooth muscle dysfunction. These mice show multiple defects including impaired smooth muscle relaxation, disturbed gastrointestinal motility and enhanced platelet adhesion.|||Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates IRAG1 and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle. http://togogenome.org/gene/10090:Spire2 ^@ http://purl.uniprot.org/uniprot/Q8K1S6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:21620703, PubMed:21983562). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (PubMed:21983562). Required for asymmetric spindle positioning and asymmetric cell division during oocyte meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (By similarity).|||Belongs to the spire family.|||Binds to actin monomers via the WH2 domain.|||Cell membrane|||Cytoplasmic vesicle membrane|||Detected in oocytes.|||The Spir-box targets binding to intracellular membrane structures.|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Cbx8 ^@ http://purl.uniprot.org/uniprot/Q9QXV1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Component of a PRC1-like complex (PubMed:16359901). Interacts with RING1, RNF2, PCGF1, PCGF2, PCGF3, BMI1, PCGF5, PCGF6 and PHC2 (PubMed:16359901). Interacts with histone H3 (By similarity). Interacts with MLLT3 (Ref.8). Interacts with PHC2 (By similarity). Interacts (via chromodomain) with single-stranded RNA (PubMed:16537902).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (By similarity).|||Nucleus http://togogenome.org/gene/10090:Sez6l ^@ http://purl.uniprot.org/uniprot/A0A0G2JG23|||http://purl.uniprot.org/uniprot/A0A0R4J0Y4|||http://purl.uniprot.org/uniprot/Q6P1D5 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SEZ6 family.|||Candidate tumor suppressor gene. May contribute to specialized endoplasmic reticulum functions in neurons.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed exclusively in the brain, predominantly in neurons. Wide expression in the gray matter of the brain with high levels in the olfactory bulb, anterior olfactory nuclei, hippocampal formation and cerebellar cortex. Detected diffusely and weakly in the white matter, such as the corpus callosum and cerebellar medulla. In the cerebellar cortex, intensely expressed in Purkinje cells and granule cells. Detected also in interneurons in the molecular layer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice lacking Sez6, Sez6l1, Sez6l2 exhibit motor discordination, and PCs are ofen innervated by multiple climbing fibers with different neuronal origins in the cerebellum. http://togogenome.org/gene/10090:Smap2 ^@ http://purl.uniprot.org/uniprot/Q7TN29 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||GTPase activating protein that acts on ARF1. Can also activate ARF6 (in vitro). May play a role in clathrin-dependent retrograde transport from early endosomes to the trans-Golgi network.|||Interacts with ARF1. Interacts with PICALM and clathrin heavy chains. http://togogenome.org/gene/10090:Ntmt2 ^@ http://purl.uniprot.org/uniprot/B2RXM4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Alpha N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes monomethylation of exposed alpha-amino group of Ala or Ser residue in the [Ala/Ser]-Pro-Lys motif and Pro in the Pro-Pro-Lys motif. Predominantly functions as a mono-methyltransferase but is also able to di-/tri-methylate the GPKRIA peptide and di-methylate the PPKRIA peptide (in vitro). May activate NTMT1 by priming its substrates for trimethylation.|||Belongs to the methyltransferase superfamily. NTM1 family.|||Nucleus http://togogenome.org/gene/10090:Kcnh2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1K0|||http://purl.uniprot.org/uniprot/O35219|||http://purl.uniprot.org/uniprot/Q53Z09 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily.|||Cell membrane|||Isoform 1 is expressed in heart, brain and testis and at low levels in lung. Isoform 3 is expressed predominantly in heart. The expression of isoform 2 is low in all tissues tested.|||Membrane|||Phosphorylated on serine and threonine residues.|||Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (By similarity).|||The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. Interacts with DNAJB12 and DNAJB14; chaperones DNAJB12 and DNAJB14 promote tetramerization (By similarity). Heteromultimer with KCNH6/ERG2 and KCNH7/ERG3 (By similarity). Interacts with ALG10B (By similarity). Heteromultimer with KCNE1 and KCNE2. Interacts with CANX. The core-glycosylated, but not the fully glycosylated form interacts with RNF207. Interacts with NDFIP1 and NDFIP2 (By similarity).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Or9g4b ^@ http://purl.uniprot.org/uniprot/Q7TR94 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gtf2a2 ^@ http://purl.uniprot.org/uniprot/Q3TE88|||http://purl.uniprot.org/uniprot/Q3TN86|||http://purl.uniprot.org/uniprot/Q80ZM7 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIA subunit 2 family.|||Intron retention.|||Nucleus|||TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation.|||TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity (By similarity).|||TFIIA is a heterodimer of the large unprocessed subunit 1 and a small subunit gamma. It was originally believed to be a heterotrimer of an alpha (p35), a beta (p19) and a gamma subunit (p12). Interacts with NCOA6 general coactivator. TFIIA forms a complex with TBP. Interacts with HSF1 (via transactivation domain). Interacts with HSF1 (via transactivation domain). Interacts with HSF1 (via transactivation domain). http://togogenome.org/gene/10090:Tsen2 ^@ http://purl.uniprot.org/uniprot/Q6P7W5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tRNA-intron endonuclease family.|||Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Probably carries the active site for 5'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events (By similarity).|||Nucleus|||nucleolus|||tRNA splicing endonuclease is a heterotetramer composed of TSEN2, TSEN15, TSEN34/LENG5 and TSEN54. tRNA splicing endonuclease complex also contains proteins of the pre-mRNA 3'-end processing machinery such as CLP1, CPSF1, CPSF4 and CSTF2 (By similarity). http://togogenome.org/gene/10090:Kctd3 ^@ http://purl.uniprot.org/uniprot/Q8BFX3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory subunit of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) up-regulating its cell-surface expression and current density without affecting its voltage dependence and kinetics.|||Belongs to the KCTD3 family.|||Brain (at protein level). Expressed in the liver kidney, and heart.|||Cell membrane|||Interacts with HCN3. http://togogenome.org/gene/10090:Engase ^@ http://purl.uniprot.org/uniprot/Q8BX80 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 85 family.|||Endoglycosidase that releases N-glycans from glycoproteins by cleaving the beta-1,4-glycosidic bond in the N,N'-diacetylchitobiose core. Involved in the processing of free oligosaccharides in the cytosol (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||cytosol http://togogenome.org/gene/10090:Mrnip ^@ http://purl.uniprot.org/uniprot/Q9D1F5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the MRE11-RAD50-NBN (MRN) damage-sensing complex; this association is constitutive. Interacts with MRE11. Interacts with NBN. Interacts with RAD50.|||Belongs to the MRNIP family.|||Nucleus|||Phosphorylated; phosphorylation is constitutive and occurs in the absence of any DNA-damaging stimulus. Phosphorylation is necessary for its nuclear retention.|||Plays a role in the cellular response to DNA damage and the maintenance of genome stability through its association with the MRN damage-sensing complex. Promotes chromatin loading and activity of the MRN complex to facilitate subsequent ATM-mediated DNA damage response signaling and DNA repair.|||nucleoplasm http://togogenome.org/gene/10090:Amer1 ^@ http://purl.uniprot.org/uniprot/Q7TS75 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Amer family.|||Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Expressed in kidney.|||In embryos, it is highly expressed in the neonatal brain and kidney and then declines substantially in the mature organs. Also expressed in lung and spleen. Expressed in the condensing metanephric mesenchyme and in early epithelial structures that are precursors to glomeruli.|||Interacts with CTNNB1, AXIN1, LRP6, KEAP1, APC and BTRC. Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes containing BTRC and/or FBXW11. Identified in the beta-catenin destruction complex containing CTNNB1, APC, AXIN1 and AXIN2. Interacts with WT1 (By similarity).|||Nucleus|||Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex. Acts both as a positive and negative regulator of the Wnt signaling pathway, depending on the context: acts as a positive regulator by promoting LRP6 phosphorylation. Also acts as a negative regulator by acting as a scaffold protein for the beta-catenin destruction complex and promoting stabilization of Axin at the cell membrane. Promotes CTNNB1 ubiquitination and degradation. Involved in kidney development (By similarity). http://togogenome.org/gene/10090:Hcfc1 ^@ http://purl.uniprot.org/uniprot/B1AUX2|||http://purl.uniprot.org/uniprot/Q61191 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Composed predominantly of six polypeptides ranging from 110 to 150 kDa and a minor 300 kDa polypeptide (PubMed:9334261). The majority of N- and C-terminal cleavage products remain tightly, albeit non-covalently, associated (By similarity). Interacts with POU2F1, CREB3, ZBTB17, EGR2, E2F4, CREBZF, SP1, GABP2, Sin3 HDAC complex (SIN3A, HDAC1, HDAC2, SUDS3), SAP30, SIN3B and FHL2 (By similarity). Component of a MLL1 complex, composed of at least the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, DPY30, E2F6, HCFC2, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8, PELP1, PHF20, PRP31, RING2, RUVBL1, RUVBL2, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (By similarity). Interacts directly with THAP3 (via its HBM) (By similarity). Interacts (via the Kelch-repeat domain) with THAP1 (via the HBM); the interaction recruits HCHC1 to the RRM1 (By similarity). Interacts directly with OGT; the interaction, which requires the HCFC1 cleavage site domain, glycosylates and promotes the proteolytic processing of HCFC1 and retains OGT in the nucleus (By similarity). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L, CXXC1, HCFC1 and DPY30 (By similarity). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (By similarity). Component of a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5; the complex is formed as a result of interactions between components of a nuclear receptor-mediated transcription complex and a histone methylation complex (By similarity). Within the complex interacts with ZNF335 (By similarity). Interacts with TET2 and TET3 (By similarity). Interacts with HCFC1R1 (By similarity). Interacts with THAP11 (PubMed:18585351). Interacts (via Kelch domain) with KMT2E (via HBM motif) (By similarity). Interacts with E2F1 (By similarity).|||Cytoplasm|||Expressed in liver, pituitary gland, skeletal muscle, kidney, eye and brain (at protein level). Also observed at low level in heart, spleen and lung.|||Nucleus|||O-glycosylated. GlcNAcylation by OGT promotes proteolytic processing.|||Proteolytically cleaved at one or several PPCE--THET sites within the HCF repeats. Further cleavage of the primary N- and C-terminal chains results in a 'trimming' and accumulation of the smaller chains. Cleavage is promoted by O-glycosylation.|||The HCF repeat is a highly specific proteolytic cleavage signal.|||The kelch repeats fold into a 6-bladed kelch beta-propeller called the beta-propeller domain which mediates interaction with HCFC1R1.|||Transcriptional coregulator (By similarity). Involved in control of the cell cycle (PubMed:9334261, PubMed:9990006). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (By similarity). Coactivator for EGR2 and GABP2 (By similarity). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription respectively) together (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (By similarity). Recruits KMT2E to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (By similarity). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity).|||Ubiquitinated. Lys-1817 and Lys-1818 are ubiquitinated both via 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. BAP1 mediated deubiquitination of 'Lys-48'-linked polyubiquitin chains; deubiquitination by BAP1 does not seem to stabilize the protein. http://togogenome.org/gene/10090:Pcgf3 ^@ http://purl.uniprot.org/uniprot/Q8BTQ0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Combined disruption of both Pcgf3 and Pcgf5 causes embryonic lethality; there are no live progeny. Male embryos are detected at 9.5 and 10.5 dpc, but are smaller than normal. Female embryos are already extensively degraded at 9.5 dpc. Placentas from male embryos have some parietal trophoblast giant cells, but fail to form a labyrinth. Placentas from female embryos lack trophoblasts altogether and fail to form a labyrinth. Defects can be attributed to the observed lack of monoubiquitination of histone H2A 'Lys-119' and lack of Xist-mediated silencing of one copy of the X chromosome.|||Component of a PRC1-like complex that contains PCGF3, RNF2 and RYBP (PubMed:28596365). Interacts with RNF2 (PubMed:28596365). Interacts with CBX6, CBX7 and CBX8 (By similarity). Interacts with BCORL1 (By similarity).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:28596365). Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity (By similarity). Plays a redundant role with PCGF5 as part of a PRC1-like complex that mediates monoubiquitination of histone H2A 'Lys-119' on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females (PubMed:28596365).|||Nucleus|||nucleoplasm http://togogenome.org/gene/10090:Arrb1 ^@ http://purl.uniprot.org/uniprot/Q8BWG8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the arrestin family.|||Cell membrane|||Constitutively phosphorylated at in the cytoplasm. At the plasma membrane, is rapidly dephosphorylated, a process that is required for clathrin binding and ADRB2 endocytosis but not for ADRB2 binding and desensitization. Once internalized, is rephosphorylated (By similarity).|||Cytoplasm|||Cytoplasmic vesicle|||Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Involved in internalization of P2RY4 and UTP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 ands subsequent recycling. Involved in the degradation of cAMP by recruiting cAMP phosphodiesterases to ligand-activated receptors. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2). ERK1/2 activated by the beta-arrestin scaffold is largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Recruits c-Src/SRC to ADRB2 resulting in ERK activation. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Inhibits ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Is required for SP-stimulated endocytosis of NK1R and recruits c-Src/SRC to internalized NK1R resulting in ERK1/2 activation, which is required for the antiapoptotic effects of SP. Is involved in proteinase-activated F2RL1-mediated ERK activity. Acts as signaling scaffold for the AKT1 pathway. Is involved in alpha-thrombin-stimulated AKT1 signaling. Is involved in IGF1-stimulated AKT1 signaling leading to increased protection from apoptosis. Involved in activation of the p38 MAPK signaling pathway and in actin bundle formation. Involved in F2RL1-mediated cytoskeletal rearrangement and chemotaxis. Involved in AGTR1-mediated stress fiber formation by acting together with GNAQ to activate RHOA. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. May serve as nuclear messenger for GPCRs. Involved in OPRD1-stimulated transcriptional regulation by translocating to CDKN1B and FOS promoter regions and recruiting EP300 resulting in acetylation of histone H4. Involved in regulation of LEF1 transcriptional activity via interaction with DVL1 and/or DVL2 Also involved in regulation of receptors other than GPCRs. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in IL8-mediated granule release in neutrophils. Binds phosphoinositides. Binds inositolhexakisphosphate (InsP6) (By similarity). Required for atypical chemokine receptor ACKR2-induced RAC1-LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. Involved in the internalization of the atypical chemokine receptor ACKR3 (By similarity). Negatively regulates the NOTCH signaling pathway by mediating the ubiquitination and degradation of NOTCH1 by ITCH. Participates in the recruitment of the ubiquitin-protein ligase to the receptor (PubMed:23886940).|||Monomer. Homodimer. Homooligomer; the self-association is mediated by InsP6-binding. Heterooligomer with ARRB2; the association is mediated by InsP6-binding. Interacts with ADRB2 (phosphorylated). Interacts with CHRM2 (phosphorylated). Interacts with LHCGR. Interacts with CYTH2 and CASR. Interacts with AP2B1 (dephosphorylated); phosphorylation of AP2B1 disrupts the interaction. Interacts (dephosphorylated at Ser-412) with CLTC. Interacts with CCR2 and GRK2. Interacts with CRR5. Interacts with PTAFR (phosphorylated on serine residues). Interacts with CLTC and MAP2K3. Interacts with CREB1. Interacts with TRAF6. Interacts with IGF1R and MDM2. Interacts with C5AR1. Interacts with PDE4D. Interacts with SRC (via the SH3 domain and the protein kinase domain); the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with TACR1. Interacts with RAF1. Interacts with DVL1; the interaction is enhanced by phosphorylation of DVL1. Interacts with DVL2; the interaction is enhanced by phosphorylation of DVL2. Interacts with IGF1R. Interacts with CHUK, IKBKB and MAP3K14. Associates with MAP kinase p38. Part of a MAPK signaling complex consisting of TACR1, ARRB1, SRC, MAPK1 (activated) and MAPK3 (activated). Part of a MAPK signaling complex consisting of F2RL1, ARRB1, RAF1, MAPK1 (activated) and MAPK3 (activated). Interacts with GPR143 (By similarity). Interacts with MAP2K4/MKK4. Interacts with HCK and CXCR1 (phosphorylated) (By similarity). Interacts with ACKR3 and ACKR4 (By similarity). Interacts with ARRDC1; the interaction is direct (PubMed:23886940). Interacts with GPR61, GPR62 and GPR135 (By similarity).|||Nucleus|||The C-terminus binds InsP6 with high affinity.|||The N-terminus binds InsP6 with low affinity.|||The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1. Binding to phosphorylated GPCRs induces a conformationanl change that exposes the motif to the surface (By similarity).|||The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2; the ubiquitination is required for rapid internalization of ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a dissociation of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such as ADRB2, induces transient ubiquitination and subsequently promotes association with USP33 (By similarity).|||clathrin-coated pit|||pseudopodium http://togogenome.org/gene/10090:Vmn1r196 ^@ http://purl.uniprot.org/uniprot/Q5SVD5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:U2af1l4 ^@ http://purl.uniprot.org/uniprot/Q8BGJ9 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the splicing factor SR family.|||Cytoplasm|||Cytoplasmic and nuclear. Displays active nucleo-cytoplasmic shuttling. Shows a circadian expression at the mRNA level.|||Interacts with GFI1, U2AF2 and C1QBP. Isoform 3 interacts with PER1.|||Isoform 3 contains a C-terminus domain with homology to Drosophila TIM (THD domain). Isoform 3 interacts with Per1 and specifically down-regulates its expression, probably by facilitating its recruitment to the proteasome. The interaction with PER1 depends on the presence of the THD domain, but the THD domain is not directly involved in the interaction.|||Isoform 3 is rapidly degraded by a proteasome-mediated degradation pathway.|||Mutant mice show defects in circadian gene expression and jet lag phenotype, but the master clock is not strongly affected. Per2 expression is rhythmic, but Per1 expression becomes nearly arrhythmic as well as Per1 target genes, such as Dbp. No splicing alteration was observed in the brain. Mutant mice show a faster adaptation to experimental jet lag, which is consistent with the circadian splicing switch providing a buffering system against sudden light changes.|||Nucleus|||Nucleus speckle|||Orthologs of U2af1l4 do not appear to exist in lower eukaryotes, Drosophila, C. elegans, plants, or vertebrates such as Xenopus or zebrafish (PubMed:11739736). Existence of splicing isoforms of U2af1l4 in human and rat is not yet proven.|||Produced by exon 7 skipping. Cytoplasm (PubMed:16819553). Shows a circadian expression at the mRNA level.|||Produced by exons 6 and 7 skipping. Produced by a circadian splicing switch in brain and liver. Contains a C-terminus domain with homology to Drosophila TIM (THD). Cytoplasmic. Shows a circadian expression at the mRNA and protein levels. Expression is quickly increased upon light exposure. Has a strongly reduced half-life compared to other isoforms.|||Produced by usage of an alternative 3' splice site in exon 8.|||RNA-binding protein that function as a pre-mRNA splicing factor. Plays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3'-splice site selection. It can functionally substitute for U2AF1 in constitutive splicing and enhancer-dependent splicing. Acts by enhancing the binding of U2AF2 to weak pyrimidine tracts. Also participates in the regulation of alternative pre-mRNA splicing. Activates exon 5 skipping of PTPRC during T-cell activation; an event reversed by GFI1. Binds to RNA at the AG dinucleotide at the 3'-splice site. Shows a preference for AGC or AGA (PubMed:11739736, PubMed:16819553, PubMed:18460468). Alternative splicing of U2AF1L4 may play a role in connecting the circadian rhythm to changing external cues: may provide a circadian buffering system in central and periphery clocks that allows synchronized adaption to clock-resetting stimuli in order to prevent potentially pathogenic desynchronization (PubMed:24837677).|||The region 162-220 is essential for the nuclear import of the protein in spite of the absence of a nuclear localization signal (NLS). This region is essential for the interaction with C1QBP, interaction which is required for the nuclear translocation. This region may be involved in the localization in nuclear dot-like structures and it also confers the ability of nucleo-cytoplasmic shuttling.|||The second zinc finger in necessary for interaction with GFI1 and for alternative pre-mRNA splicing events.|||Ubiquitous. Highly expressed in the brain.|||Up-regulated in response to T-cell activation (at protein level) (PubMed:16819553). Circadian alternative splicing switch accounts for rhythmic isoform expression. A circadian splicing switch produces isoform 3 in the brain cerebellum and liver (at protein level). Isoform 3 expression is regulated with the circadian rhythm but is also quickly increased upon light exposure (4-8 hours after light exposure). Expression of isoform 3 changes approximately 5-fold across a period of 24 hours, with concomitant changes in isoform 1, resulting in total U2af1l4 remaining constant (PubMed:24837677). http://togogenome.org/gene/10090:Catsperz ^@ http://purl.uniprot.org/uniprot/Q9CQP8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation (PubMed:28226241, PubMed:31056283, PubMed:34225353). Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization (PubMed:28226241, PubMed:31056283). Required for a distribution of the CatSper complex in linear quadrilateral nanodomains along the flagellum, maximizing fertilization inside the mammalian female reproductive tract (PubMed:28226241). Together with EFCAB9, associates with the CatSper channel pore and is required for the two-row structure of each single CatSper channel (PubMed:31056283).|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:28226241). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (Probable). Interacts with EFCAB9; the interaction is direct, Ca(2+)-dependent and connects EFCAB9 with the CatSper complex (PubMed:31056283). Dissociates from EFCAB9 at elevated pH (PubMed:31056283).|||Mice are normal but males show severe male subfertility. Mutant males display fragmented patterns of CatSper complex stripes in the tails of their sperm, leading to a reduction of calcium ions that pass through the channels to enter the cell. As consequence, the sperm tail is more rigid, preventing it from moving efficiently within the female. Mutant sperm are less able to penetrate the egg than normal sperm.|||Testis-specific (PubMed:20339383, PubMed:28226241). Expressed in adult but not in fetal testis (PubMed:20339383). Not expressed in ovary. Within testis, expression is restricted to spermatids (PubMed:20339383).|||flagellum membrane http://togogenome.org/gene/10090:Nipsnap3a ^@ http://purl.uniprot.org/uniprot/G3X8S9|||http://purl.uniprot.org/uniprot/Q9D9L2 ^@ Similarity ^@ Belongs to the NipSnap family. http://togogenome.org/gene/10090:Hydin ^@ http://purl.uniprot.org/uniprot/Q80W93 ^@ Caution|||Developmental Stage|||Disease Annotation|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15 dpc, expressed in developing choroid plexus. At P0, brain expression is limited to the ciliated ependymal cells.|||Contaminating sequence. Sequence of unknown origin in the C-terminal part.|||Defects in Hydin are the cause of spontaneous hydrocephalus 3, a lethal communicating hydrocephalus with perinatal onset. There is lethality in the first weeks of life because of hydrocephalus caused by abnormal ependymal ciliary motility. Cilia are unable to bend normally, ciliary beat frequency is reduced, and the cilia tend to stall. As a result, these cilia are incapable of generating fluid flow. Similar defects are observed for cilia in trachea. Mice do not exhibit randomization of left-right body asymmetry or situs inversus.|||Expressed in brain and testis. Expressed in ciliated epithelial cells lining bronchi and oviduct, and in spermatocytes.|||Interacts with KIF9.|||It is uncertain whether Met-1 or Met-56 is the initiator.|||Required for ciliary motility.|||cilium|||cilium axoneme http://togogenome.org/gene/10090:Cdc37l1 ^@ http://purl.uniprot.org/uniprot/Q9CZP7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDC37 family.|||Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.|||Cytoplasm|||Self-associates. Forms complexes with Hsp70 and Hsp90. Interacts with CDC37, FKBP4, PPID and STIP1. http://togogenome.org/gene/10090:Klc3 ^@ http://purl.uniprot.org/uniprot/Q91W40 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the kinesin light chain family.|||Expressed in postmeiotic male germ cells (at protein level) (PubMed:11319135). Expressed in the testes (at protein level) (PubMed:35547804). Expressed in spleen, intestine, brain and ovary (PubMed:11319135).|||Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. Plays a role during spermiogenesis in the development of the sperm tail midpiece and in the normal function of spermatozoa (PubMed:22561200). May play a role in the formation of the mitochondrial sheath formation in the developing spermatid midpiece (PubMed:22561200).|||Male transgenic mice (expressing a KLC3 deletion mutant) display significantly reduced reproductive efficiency siring small sized litters (PubMed:22561200). Show significantly reduced sperm count, defective mitochondrial sheath structure in a number of spermatids and produce spermatozoa that exhibit abnormal motility parameters (PubMed:22561200).|||Mitochondrion|||Oligomer composed of two heavy chains and two light chains (By similarity). Associates with microtubulin in an ATP-dependent manner (By similarity). Interacts with KIF5C. Interacts with ODF1 (By similarity). Interacts with LRGUK (PubMed:28003339). Interacts with VDAC2 (PubMed:22561200).|||The heptad repeat (HR) motif is sufficient for interaction with kinesin heavy (KHL) chains and ODF1. The TPR region is involved in mitochondrial binding (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Lrrfip1 ^@ http://purl.uniprot.org/uniprot/A0A087WPK3|||http://purl.uniprot.org/uniprot/A6H5U5|||http://purl.uniprot.org/uniprot/G5E8E1|||http://purl.uniprot.org/uniprot/Q3UZ39|||http://purl.uniprot.org/uniprot/Q8BLV4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRFIP family.|||Cytoplasm|||Homodimer. May also form higher oligomers. Interacts with FLII. Interacts with MYD88 (By similarity). Competes with FLII for MyD88-binding, even in the absence of LPS (By similarity).|||Nucleus|||The DNA-binding domain is intrinsically unstructured.|||The coiled coil mediates dimerization.|||Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA (By similarity). Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding (By similarity).|||Ubiquitously expressed. http://togogenome.org/gene/10090:Prkcg ^@ http://purl.uniprot.org/uniprot/P63318|||http://purl.uniprot.org/uniprot/Q2NKI4|||http://purl.uniprot.org/uniprot/Q3UN66 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.|||Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contribute to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (PubMed:23185022).|||Cell membrane|||Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-514 (activation loop of the kinase domain), Thr-655 (turn motif) and Thr-674 (hydrophobic region), need to be phosphorylated for its full activation.|||Cytoplasm|||Expressed in the cerebellum, cerebral cortex and hippocampus (at protein level). Highly expressed in Purkinje cells.|||Interacts with CDCP1 and GRIA4 (By similarity). Interacts with TP53INP1 and p53/TP53 (By similarity). Interacts with BMAL1.|||Membrane|||Mice exhibit impaired motor coordination due to the inability to eliminate multiple climbing fibers during innervation of Purkinje cells. 40% of Purkinje cells are still innervated by multiple climbing fibers. Exhibit food-anticipatory activity comparable to that of wild type mice but they do not reduce their late night activity or adapt their food intake amount to restricted feeding as efficiently as wild type mice.|||Ubiquitinated.|||dendrite|||perinuclear region|||synaptosome http://togogenome.org/gene/10090:Ramp2 ^@ http://purl.uniprot.org/uniprot/Q9WUP0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RAMP family.|||Heterodimer of CALCRL and RAMP2.|||Membrane|||Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for adrenomedullin (AM) together with CALCRL.|||Ubiquitous. Expressed predominantly in embryonic brain, lung and gut and in adult heart, lung, skeletal muscle and brain. http://togogenome.org/gene/10090:Sema5b ^@ http://purl.uniprot.org/uniprot/Q60519 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Differentially expressed in embryonic and adult tissues (PubMed:8817451). Its abundance decreases from 10 dpc to birth (PubMed:8817451).|||In adult, only detected in brain.|||May act as a positive axonal guidance cue.|||Membrane http://togogenome.org/gene/10090:Pcsk2 ^@ http://purl.uniprot.org/uniprot/P21661|||http://purl.uniprot.org/uniprot/Q547J8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S8 family.|||Belongs to the peptidase S8 family. Furin subfamily.|||Secreted|||Serine endopeptidase which is involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells (By similarity).|||secretory vesicle http://togogenome.org/gene/10090:Gorab ^@ http://purl.uniprot.org/uniprot/Q8BRM2 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GORAB family.|||Cytoplasm|||Expressed in small intestine, kidney, skeletal muscle, lung, spleen, brain and heart. High expression is observed in osteoblasts and skin; also expressed in osteoclasts albeit at lower levels.|||Golgi apparatus|||Interacts with RCHY1 (By similarity). Interacts with SCYL1 and RAB6A/RAB6. http://togogenome.org/gene/10090:Ihh ^@ http://purl.uniprot.org/uniprot/P97812|||http://purl.uniprot.org/uniprot/Q80XI9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Almost half of homozygous embryos mice for IHH died between 10.5 and 12.5 dpc. Also some lethality occurred in late gestation, most of the remaining embryos developed to term but died at birth, due to respiratory failure. Mutants display markedly reduced chondrocyte proliferation, maturation of chondrocytes at inappropriate position, and a failure of osteoblast development in endochondral bones.|||Belongs to the hedgehog family.|||Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.|||Cell membrane|||Cholesterylation is required for N-product targeting to lipid rafts and multimerization.|||Detected at 10 dpc in developing gut, at 14.5 days dpc in the cartilage primordium and in the developing urogenital sinus. Expression increases with gestional age in kidney and duodenum, becoming maximal in adulthood.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||In the adult kidney, found in proximal convoluted and proximal straight tubule.|||Interacts with BOC and CDON. Interacts with PTCH1 (By similarity). Interacts with glypican GPC3 (PubMed:23665349).|||Membrane|||Multimer.|||N-palmitoylation by HHAT of N-product is required for indian hedgehog protein N-product multimerization and full activity.|||Secreted|||The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). The N-product is the active species in both local and long-range signaling, whereas the C-product is degraded in the reticulum endoplasmic (By similarity).|||The C-terminal part of the hedgehog protein precursor displays an autoproteolysis activity that results in the cleavage of the full-length protein into two parts (N-product and C-product). In addition, the C-terminal part displays a cholesterol transferase activity that results by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product.|||The C-terminal part of the indian hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Plays a role in hedgehog paracrine signaling. Associated with the very-low-density lipoprotein (VLDL) particles to function as a circulating morphogen for endothelial cell integrity maintenance (By similarity).|||The dually lipidated hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development.|||The dually lipidated indian hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development. Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). Plays a role in morphogenesis of the skeleton by coordinating growth and differentiation of the endochondral skeleton (PubMed:10465785, PubMed:10631175). Positively regulates PTHLH during endochondral bone formation preventing chondrocyte hypertrophy. In contrast, Ihh is necessary for normal chondrocyte proliferation in a PTHLH-independent pathway (PubMed:10631175). http://togogenome.org/gene/10090:Tmem169 ^@ http://purl.uniprot.org/uniprot/Q8BG50 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Slc6a20a ^@ http://purl.uniprot.org/uniprot/Q8VDB9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A20 subfamily.|||Expressed in brain, kidney, small intestine, thymus, spleen and lung. In the brain, expressed in cerebellum, cortex and brain stem. Not detected in liver, muscle or heart (PubMed:15689184). In brain, widespread in various regions, including the meninges, choroid plexus, cortex, hippocampus and thalamus (PubMed:33428810).|||Expression in kidney is highly induced 3 days after birth.|||Mediates the Na(+)- and Cl(-)-dependent uptake of imino acids such as L-proline, N-methyl-L-proline and pipecolate as well as N-methylated amino acids (PubMed:15689184). Also transports glycine, regulates proline and glycine homeostasis in the brain playing a role in the modulation of NMDAR currents (PubMed:33428810). http://togogenome.org/gene/10090:Ly6m ^@ http://purl.uniprot.org/uniprot/Q9CQ11 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Wdr11 ^@ http://purl.uniprot.org/uniprot/Q8K1X1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Broadly expressed in various organs including brain, eye,ear, lung, heart, kideny and gonads (PubMed:29263200). Cerebral cortex. The entire developing central nervous system, except for the spinal cord, reveals expression. Expressed in the neuroepithelium, including the diencephalic region that gives rise to hypothalamic neurons. In the adult brain, intense expression is restricted to the olfactory bulb, the olfaction-related piriform cortex, the granule cell layer of the cerebellum, and neurons of the hippocampal formation. The brain demonstrated expression scattered throughout the hypothalamus, sometimes in clusters of neurons (PubMed:20887964).|||Component of the complex WDR11 composed of C17orf75, FAM91A1 and WDR11; FAM91A1 and WDR11 are required for proper location of the complex (By similarity). Interacts with GLI3; the interaction associateS EMX1 with GLI3 (PubMed:29263200). Interacts with TBC1D23; this interaction may be indirect and recruits TBC1D23 to AP-1-derived vesicles (PubMed:29084197). Interacts (via the N-terminal and the central portion of the protein) with EMX1 (PubMed:29263200).|||Cytoplasm|||Cytoplasmic vesicle|||Expressed in embryos from 10.5. to 14.5 dpc (PubMed:20887964, PubMed:29263200). In 10.5-12.5 dpc embryos, detected in the vesicles of the heart, branchial arches, mesonephric duct, head mesenchyme, developing eye and forebrain (PubMed:29263200). At 12.5 and 14.5 dpc, high levels of expression are particularly noteworthy in the developing cortex and the olfactory bulb (PubMed:20887964, PubMed:29263200).|||Involved in the Hedgehog (Hh) signaling pathway, is essential for normal ciliogenesis (PubMed:29263200). Regulates the proteolytic processing of GLI3 and cooperates with the transcription factor EMX1 in the induction of downstream Hh pathway gene expression and gonadotropin-releasing hormone production (PubMed:29263200). WDR11 complex facilitates the tethering of Adaptor protein-1 complex (AP-1)-derived vesicles. WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1 (By similarity).|||Mutants show retardation of growth and development with mid-gestation embryonic lethality, delayed puberty, reproductive dysfunctions and obesity. The rare mutant survivors through adulthood exhibit abnormal digit separation and syndactyly, as well as shortened limbs and hypoplastic skeletons with reduced or absent bone mineralization. Their head show a diminutive and curved nasal midline and a small lower jaw with microcephaly, closely spaced eyes or single/absent eyes. They have hypothalamic gonadotropin-releasing hormone (GnRH) deficiency and pituitary dysgenesis. In some cases, they exhibit exencephaly. At 12.5 dpc, they also have heart defects with a double-outlet right ventricle, ventricular septal defects and sometimes thorcic skeletal defect and lung airway abnormalities (PubMed:29263200). Mutant cells show defective ciliogenesis with a significant reduction in the length of the ciliary axoneme and the frequency of ciliated cells (PubMed:29263200).|||Nucleus|||cilium axoneme|||cilium basal body|||trans-Golgi network http://togogenome.org/gene/10090:Il27 ^@ http://purl.uniprot.org/uniprot/Q8K3I6 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with EBI3 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR which appears to be required but not sufficient for IL-27-mediated signal transduction. IL-27 potentiate the early phase of TH1 response and suppress TH2 and TH17 differentiation. It induces the differentiation of TH1 cells via two distinct pathways, p38 MAPK/TBX21- and ICAM1/ITGAL/ERK-dependent pathways. It also induces STAT1, STAT3, STAT4 and STAT5 phosphorylation and activates TBX21/T-Bet via STAT1 with resulting IL12RB2 up-regulation, an event crucial to TH1 cell commitment. It suppresses the expression of GATA3, the inhibitor TH1 cells development. In CD8 T-cells, it activates STATs as well as GZMB. IL-27 reveals to be a potent inhibitor of TH17 cell development and of IL-17 production. Indeed IL27 alone is also able to inhibit the production of IL17 by CD4 and CD8 T-cells. While IL-27 suppressed the development of pro-inflammatory Th17 cells via STAT1, it inhibits the development of anti-inflammatory inducible regulatory T-cells, iTreg, independently of STAT1. IL-27 has also an effect on cytokine production, it suppresses pro-inflammatory cytokine production such as IL2, IL4, IL5 and IL6 and activates suppressors of cytokine signaling such as SOCS1 and SOCS3. Apart from suppression of cytokine production, IL-27 also antagonizes the effects of some cytokines such as IL6 through direct effects on T-cells. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines such as IP-10/CXCL10 and MIG/CXCL9.|||Belongs to the IL-6 superfamily.|||By LPS and Interferon gamma in primary astrocytes and microglia. Induced by Toll-like receptor ligand in dendritic cells. Inhibited by PPAR-alpha agonist such as fenofibrate and produced by TNF-alpha in microglia.|||Expressed in macrophages and dendritic cells.|||Heterodimer with EBI3; not disulfide-linked. This heterodimer is known as interleukin IL-27.|||In mouse models of experimental autoimmune encephalitis (EAE) induced by Toxoplasma Gondi infection, brain levels of IL-27 are massively increased. Deficiency of IL-27 receptors in this mouse model with EAE induces development of a more severe neuroinflammation than in wild-type mice with EAE. This excessive neuroinflammation is associated with increased numbers of TH17 cells in the central nervous system (CNS). Continuous administration of IL-27 to EAE mice produces a strong suppressive effect on active EAE, with reduced CNS infiltration of TH17 cells and TH17 cells activity.|||Mice injected with B16F10 tumor cells develop tumors and lung metastasis. In mice injected with B16F10 tumor cells stably transfected with IL-27, tumor cells grow much more slowly and the number of pulmonary metastasis is markedly reduced. IL-27 exhibits a strong antitumor activity as well as antiangiogenic activity with massive decreased of microvessels density in lung metastasis. Similarly, mice injected with C26 colon tumor cells transfected with IL-27 acquire tumor-specific protective activity and exhibit minimal tumor growth with enhanced IFN-gamma production. This antitumor activity is abolished in TBX21-deficient mice. Neuroblastoma cells overexpressing IL-27 also demonstrate markedly delayed growth; This tumor regression appears to be dependent on CD8 cells.|||O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Dgka ^@ http://purl.uniprot.org/uniprot/O88673 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Also plays an important role in the biosynthesis of complex lipids. Can also phosphorylate 1-alkyl-2-acylglycerol in vitro as efficiently as diacylglycerol provided it contains an arachidonoyl group. Also involved in the production of alkyl-lysophosphatidic acid, another bioactive lipid, through the phosphorylation of 1-alkyl-2-acetyl glycerol.|||Monomer.|||Stimulated by calcium and phosphatidylserine.|||cytosol http://togogenome.org/gene/10090:Rnpep ^@ http://purl.uniprot.org/uniprot/E9PYF1|||http://purl.uniprot.org/uniprot/Q8BMH2|||http://purl.uniprot.org/uniprot/Q8VCT3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Exopeptidase which selectively removes arginine and/or lysine residues from the N-terminus of several peptide substrates including Arg(0)-Leu-enkephalin, Arg(0)-Met-enkephalin and Arg(-1)-Lys(0)-somatostatin-14. Can hydrolyze leukotriene A4 (LTA-4) into leukotriene B4 (LTB-4) (By similarity).|||Monomer.|||Secreted http://togogenome.org/gene/10090:Or1ad1 ^@ http://purl.uniprot.org/uniprot/Q8VGH1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plxdc2 ^@ http://purl.uniprot.org/uniprot/Q9DC11 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Expressed in tumor endothelium and in vessels of some normal tissues, such as the muscle and lung.|||Interacts with CTTN.|||May play a role in tumor angiogenesis.|||Membrane http://togogenome.org/gene/10090:Tbc1d10c ^@ http://purl.uniprot.org/uniprot/Q8C9V1 ^@ Domain|||Function|||Subunit ^@ Inhibits the Ras signaling pathway through its intrinsic Ras GTPase-activating protein (GAP) activity. Acts as a negative feedback inhibitor of the calcineurin signaling pathway that also mediates crosstalk between calcineurin and Ras (By similarity).|||Interacts with both calcineurin and HRAS.|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site. http://togogenome.org/gene/10090:Pde1c ^@ http://purl.uniprot.org/uniprot/A0A0N4SWG4|||http://purl.uniprot.org/uniprot/A0A5F8MPG4|||http://purl.uniprot.org/uniprot/E9Q7V6|||http://purl.uniprot.org/uniprot/Q3USZ6|||http://purl.uniprot.org/uniprot/Q5D0E7|||http://purl.uniprot.org/uniprot/Q64338|||http://purl.uniprot.org/uniprot/Q8CDV2|||http://purl.uniprot.org/uniprot/Q9D5W0 ^@ Activity Regulation|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.|||Calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:8810348). Exhibits high affinity for both cAMP and cGMP (By similarity). Modulates the amplitude and duration of the cAMP signal in sensory cilia in response to odorant stimulation, hence contributing to the generation of action potentials. Regulates smooth muscle cell proliferation. Regulates the stability of growth factor receptors, including PDGFRB (Probable).|||Exhibits a higher sensitivity to Ca(2+) stimulation than isoforms 1 and 2 (PubMed:8810348).|||Expressed at a moderate level in brain, the cerebellum, testis, heart and olfactory epithelium.|||Highly expressed in olfactory epithelium and at very low levels, if any, in other tissues (PubMed:8810348). In the cochlea, expressed in the inner and outer hair cells (at protein level) (PubMed:29860631). In the brain, highly expressed in the neurons of the granule layer of the cerebellum, some Purkinje cells, the central amygdaloid nucleus, and the interpolar spinal trigem nucleus and, at moderate levels, in the glomerular and external plexiform layer of the olfactory bulb as well as in parts of the caudate-putamen and olfactory tubercle (PubMed:8810348).|||Highly expressed in testis and at moderate levels in heart.|||Homodimer.|||Lysosome|||PDE1C4 and PDE1C5 isoforms differ at the level of the 3'-UTR.|||Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+) (PubMed:8810348). Different splice variants may have different sensitivities to Ca(2+) (PubMed:8810348). http://togogenome.org/gene/10090:Ugt2b35 ^@ http://purl.uniprot.org/uniprot/Q8BJL9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Fam120c ^@ http://purl.uniprot.org/uniprot/Q3V3X9|||http://purl.uniprot.org/uniprot/Q8C3F2 ^@ Similarity ^@ Belongs to the constitutive coactivator of PPAR-gamma family. http://togogenome.org/gene/10090:Slc12a6 ^@ http://purl.uniprot.org/uniprot/Q3V0N8|||http://purl.uniprot.org/uniprot/Q924N4 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the SLC12A transporter family.|||Cell membrane|||Defects in Slc12a6 are a cause of locomotor abnormalities beginning at 2 weeks of age. Slc12a6 deficient mice show hypomyelination, decompaction of myelin, demyelination, axonal swelling and fiber degeneration.|||Expressed in hippocampus and corpus callosum (at protein level) (PubMed:18566107). Highly expressed throughout the brain and detected at lower levels in kidney. Highly expressed in highly myelinated white matter of the brain, but not in gray matter. Detected in the corpus callosum, in packed cell layers of the hippocampus and in Purkinje neurons within the cerebellum. Highly expressed in white matter in the spinal cord, but not in dorsal root ganglia or sciatic nerve. Colocalizes with the oligodendrocyte marker CNP. Expressed in hippocampus in CA1, and to a lesser extent CA3 pyramidal cells (PubMed:12368912). Also expressed in cortex, mostly in large neurons and in the large cerebellar Purkinje cells (PubMed:12368912).|||Highly expressed in kidney, but not detected in brain.|||Homodimer (By similarity). Homomultimer and heteromultimer with other K-Cl cotransporters. Interacts (via C-terminus) with CKB; the interaction may be required for SLC12A6 potassium-chloride cotransport activity (By similarity).|||Inhibited following phosphorylation by OXSR1/OSR1 and STK39/SPAK: phosphorylation takes place downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4) in response to hyperosmotic stress and subsequent cell shrinkage.|||Locomotor abnormalities beginning at 2 weeks of age (PubMed:12368912). Hypomyelination, decompaction of myelin, demyelination, axonal swelling and fiber degeneration (PubMed:12368912).|||Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (By similarity). May contribute to cell volume homeostasis in single cells (By similarity).|||Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10347194, PubMed:31649201). May contribute to cell volume homeostasis in single cells (Probable).|||Membrane|||N-glycosylated.|||N-terminal loop binds to the intracellular vestibule of the transporter, arresting the transporter in an inhibited state.|||Phosphorylated, phosphorylation regulates transporter activity. Phosphorylated at Thr-991 and Thr-1048 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity. http://togogenome.org/gene/10090:Kdm4a ^@ http://purl.uniprot.org/uniprot/A2A8L9|||http://purl.uniprot.org/uniprot/Q8BW72 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JHDM3 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:24953653). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively (By similarity).|||Interacts with histone deacetylase proteins HDAC1, HDAC2 and HDAC3. Interacts with RB and NCOR1 (By similarity).|||Nucleus|||The 2 Tudor domains recognize and bind methylated histone H3 'Lys-4' residue (H3K4me). Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails. Trimethylated H3 'Lys-4' (H3K4me3) is bound in a cage of 3 aromatic residues, 2 of which are from the Tudor domain 2, while the binding specificity is determined by side-chain interactions involving residues from the Tudor domain 1. The Tudor domains are also able to bind trimethylated histone H3 'Lys-9' (H3K9me3), di- and trimethylated H4 'Lys-20' (H4K20me2 and H4K20me3). Has high affinity for H4K20me2, blocking recruitment of proteins such as TP53BP1 (By similarity).|||Ubiquitinated by RNF8 and RNF168, leading to its degradation (PubMed:24953653). Degradation promotes accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited (By similarity).|||Widely expressed. http://togogenome.org/gene/10090:Otud5 ^@ http://purl.uniprot.org/uniprot/Q3U2S4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C85 family.|||Deubiquitinating enzyme that functions as negative regulator of the innate immune system. Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro). Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production. Controls neuroectodermal differentiation through cleaving 'Lys-48'-linked ubiquitin chains to counteract degradation of select chromatin regulators such as ARID1A, HDAC2 and HCF1. Acts as a positive regulator of mTORC1 and mTORC2 signaling following phosphorylation by MTOR: acts by mediating deubiquitination of BTRC, leading to its stability.|||Inhibited by N-ethyl-maleimide (NEM).|||Interacts with TRAF3.|||Mutant mice die at the embryo stage.|||Nucleus|||Phosphorylation at Ser-177 is required for deubiquitinating activity. Phosphorylation at Ser-323, Ser-332 and Ser-503 by MTOR promotes its activity. http://togogenome.org/gene/10090:Tbck ^@ http://purl.uniprot.org/uniprot/Q8BM85 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily.|||Cytoplasm|||Involved in the modulation of mTOR signaling and expression of mTOR complex components. Involved in the regulation of cell proliferation and growth. Involved in the control of actin-cytoskeleton organization.|||Midbody|||The protein kinase domain is predicted to be catalytically inactive.|||spindle http://togogenome.org/gene/10090:Slc44a3 ^@ http://purl.uniprot.org/uniprot/Q921V7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CTL (choline transporter-like) family.|||Membrane http://togogenome.org/gene/10090:Srp9 ^@ http://purl.uniprot.org/uniprot/P49962|||http://purl.uniprot.org/uniprot/Q3UIK3|||http://purl.uniprot.org/uniprot/Q5EAT0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SRP9 family.|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (By similarity). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP (By similarity). The complex of SRP9 and SRP14 is required for SRP RNA binding (By similarity).|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP. The complex of SRP9 and SRP14 is required for SRP RNA binding.|||Cytoplasm|||Heterodimer with SRP14; binds RNA as heterodimer (By similarity). Component of a signal recognition particle complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9 (PubMed:9233785). http://togogenome.org/gene/10090:Kif15 ^@ http://purl.uniprot.org/uniprot/Q6P9L6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KLP2 subfamily.|||Cytoplasm|||Expressed in brain (neurons in the external germinal layer of the cerebellum and in ventricular zones) (at protein level). Expressed in spleen and testis.|||Interacts with MKI67 and TPX2.|||Plus-end directed kinesin-like motor enzyme involved in mitotic spindle assembly.|||spindle http://togogenome.org/gene/10090:Dgke ^@ http://purl.uniprot.org/uniprot/Q9R1C6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Cytoplasm|||Highly expressed in brain and heart (PubMed:11287665). In brain, highly expressed in Purkinje cells of the cerebellum, pyramidal cells of the hippocampus, mitral cells of the olfactory bulb, and neurons of the substantia nigra (PubMed:11287665). Lower expression in neurons of the thalamus, superior olive, and lateral reticular nucleus is also detected (PubMed:11287665). Expressed in platelets (PubMed:23542698).|||Homozygous knockout mice are normal, reproduce and behave normally. No gross or histological abnormalities in major organs, including the brain are observed (PubMed:11287665). The phosphatidylinositol 4,5- bisphosphate-signaling pathway in cerebral cortex and long-term potentiation are affected (PubMed:11287665).|||Membrane|||Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:11287665). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:11287665). Also plays an important role in the biosynthesis of complex lipids (By similarity). Displays specificity for diacylglycerol substrates with an arachidonoyl acyl chain at the sn-2 position, with the highest activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol the main diacylglycerol intermediate within the phosphatidylinositol turnover cycle (PubMed:11287665, PubMed:19744926). Can also phosphorylate diacylglycerol substrates with a linoleoyl acyl chain at the sn-2 position but much less efficiently (By similarity). http://togogenome.org/gene/10090:Aif1l ^@ http://purl.uniprot.org/uniprot/Q9EQX4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Actin-binding protein that promotes actin bundling. May neither bind calcium nor depend on calcium for function (By similarity).|||Homodimer (Potential). Monomer (By similarity).|||cytoskeleton|||ruffle membrane http://togogenome.org/gene/10090:Ddx18 ^@ http://purl.uniprot.org/uniprot/B2RUM8|||http://purl.uniprot.org/uniprot/Q8K363 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX18/HAS1 subfamily.|||Chromosome|||Interacts with NOL8; the interaction is RNA-dependent.|||Probable RNA-dependent helicase.|||RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.|||nucleolus http://togogenome.org/gene/10090:Amz2 ^@ http://purl.uniprot.org/uniprot/B1AT59|||http://purl.uniprot.org/uniprot/Q400C8 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase M54 family.|||Binds 2 Zn(2+) ions per subunit. One is catalytic, whereas the other seems to have a structural role.|||Expression in testis begins at about postnatal day 10 (P10), with adult level of expression reached at P20.|||Predominantly expressed in testis.|||Probable zinc metalloprotease. http://togogenome.org/gene/10090:Rhox4c ^@ http://purl.uniprot.org/uniprot/Q2MDG1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sparc ^@ http://purl.uniprot.org/uniprot/P07214|||http://purl.uniprot.org/uniprot/Q5NCU4|||http://purl.uniprot.org/uniprot/Q5NCU5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Appears to regulate cell growth through interactions with the extracellular matrix and cytokines. Binds calcium and copper, several types of collagen, albumin, thrombospondin, PDGF and cell membranes. There are two calcium binding sites; an acidic domain that binds 5 to 8 Ca(2+) with a low affinity and an EF-hand loop that binds a Ca(2+) ion with a high affinity.|||Belongs to the SPARC family.|||Expressed at high levels in tissues undergoing morphogenesis, remodeling and wound repair.|||Membrane|||N-glycosylated.|||basement membrane http://togogenome.org/gene/10090:Ubb ^@ http://purl.uniprot.org/uniprot/P0CG49 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin family.|||Cytoplasm|||Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.|||For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.|||Interacts with SKP1-KMD2A and SKP1-KMD2B complexes.|||Mitochondrion outer membrane|||Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.|||Nucleus|||Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30.|||Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. http://togogenome.org/gene/10090:Rnf146 ^@ http://purl.uniprot.org/uniprot/Q9CZW6 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can form homooligomers. Interacts with PARsylated AXIN1, AXIN2, BLZF1, CASC3, H1-2, IPO7, LIG3, NCL, PARP1, XRCC1, XRCC5 and XRCC6. Interacts with DDB1, DHX15, IQGAP1, LRPPRC, PARP2, PRKDC, RUVBL2, TNKS1 and TNKS2. Binding often leads to interactor ubiquitination, in the presence of the appropriate E1 and E2 enzymes, and proteasomal degradation.|||E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein (By similarity). Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos (PubMed:21602803, PubMed:21825151). Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner (PubMed:21602803, PubMed:21825151). Does not affect PARP1 activation. Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest (PubMed:21602803, PubMed:21825151). Promotes cell survival after gamma-irradiation. Facilitates DNA repair (By similarity).|||Expressed at relatively high levels in the brain. Also present in spleen, heart, kidney, testis and liver. In the brain, expressed in the cerebellum, hippocampus, striatum, cortex, frontal cortex and, at lowest levels, in olfactory bulb (at protein level). Predominantly expressed in neurons.|||Nucleus|||The WWE domain mediates non-covalent PAR-binding.|||Ubiquitinated; autoubiquitinated. Autoubiquitination is enhanced upon PAR-binding (By similarity).|||Up-regulated in cortical neurons by treatment with N-methyl-D-aspartate (NMDA). Toxic doses of NMDA fail to induce Iduna expression. Sublethal exposure to oxygen-glucose deprivation also induces Iduna protein expression. Also induced by treatments that result in resistance to subsequent ischemic injury, such as 5 minute bilateral common carotid artery occlusion (at protein level).|||Was named Iduna after the Norse goddess of protection and eternal youth.|||cytosol http://togogenome.org/gene/10090:Or6c2b ^@ http://purl.uniprot.org/uniprot/Q8K501 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pla2r1 ^@ http://purl.uniprot.org/uniprot/Q62028 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ C-type lectin domains 3-5 mediate the interaction with phospholipase PLA2G1B.|||Cell membrane|||Following exposure to endotoxin (at protein level).|||Interacts with sPLA2-IB/PLA2G1B; this interaction mediates intracellular signaling as well as clearance of extracellular sPLA2-IB/PLA2G1B via endocytotic pathway (PubMed:10066760). Interacts with sPLA2-X/PLA2G10; this interaction mediates sPLA2-X/PLA2G10 clearance and inactivation (PubMed:10922494, PubMed:11741598).|||Mice are viable, fertile and without evident histopathological abnormalities. After challenge with bacterial lipopolysaccharide (LPS), they exhibit longer survival than wild-type mice. They are also resistant to lethal effects of exogenous sPLA2-IB/PLA2G1B after sensitization with sublethal dose of LPS, suggesting a potential role in the progression of endotoxic shock.|||Receptor for secretory phospholipase A2 (sPLA2). Acts as a receptor for phospholipases sPLA2-IB/PLA2G1B, sPLA2-X/PLA2G10 and, with lower affinity, sPLA2-IIA/PLA2G2A. Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in pro-inflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B and sPLA2-X/PLA2G10. In podocytes, binding of sPLA2-IB/PLA2G1B can regulate podocyte survival and glomerular homeostasis.|||Secreted|||The endocytosis signal probably mediates endocytosis via clathrin-coated pits.|||The secretory phospholipase A2 receptor form may be produced by the action of metalloproteinases. It contains all extracellular domains and only lacks transmembrane and cytosolic regions. It is however unclear whether this form is produced by proteolytic cleavage as suggested by some experiments reported by PubMed:11830583, or by alternative splicing.|||Widely expressed. Present in type II alveolar epithelial cells and a subset of splenic lymphocytes. Present at the surface of polymorphonuclear neutrophils (at protein level). http://togogenome.org/gene/10090:Fn1 ^@ http://purl.uniprot.org/uniprot/A0A087WR50|||http://purl.uniprot.org/uniprot/A0A087WS56|||http://purl.uniprot.org/uniprot/A0A087WSN6|||http://purl.uniprot.org/uniprot/B7ZNJ1|||http://purl.uniprot.org/uniprot/B9EHT6|||http://purl.uniprot.org/uniprot/P11276|||http://purl.uniprot.org/uniprot/Q3TBB4|||http://purl.uniprot.org/uniprot/Q3UGY5|||http://purl.uniprot.org/uniprot/Q3UH17|||http://purl.uniprot.org/uniprot/Q3UHL6|||http://purl.uniprot.org/uniprot/Q3UHR1|||http://purl.uniprot.org/uniprot/Q3UZF9 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.|||Expressed in the inner limiting membrane and around blood vessels in the retina (at protein level) (PubMed:29777959). Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix.|||Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin (By similarity). Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape healing, and maintenance of cell shape (By similarity). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (PubMed:21768292). Participates in the regulation of type I collagen deposition by osteoblasts (PubMed:21768292). Acts as a ligand for the Lilrb4a receptor, inhibiting Fcgr1/CD64-mediated monocyte activation (PubMed:34089617).|||Forms covalent cross-links mediated by a transglutaminase, such as F13A or TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers (e.g. fibrinogen-fibronectin, collagen-fibronectin heteropolymers).|||Glucocorticoids suppressed mRNA expression and protein synthesis.|||Mostly heterodimers or multimers of alternatively spliced variants, connected by 2 disulfide bonds near the carboxyl ends; to a lesser extent homodimers. Interacts with FBLN1, AMBP, TNR, LGALS3BP and COL13A1. Interacts with FBLN7 (By similarity). Interacts with COMP. Interacts (via type III repeats 9-14) with TNFAIP6 (via CUB domain); this interaction enhances fibronectin fibril assembly. TNFAIP6 may act as a bridging molecule between FN1 and THBS1 (By similarity). Interacts with TNR; the interaction inhibits cell adhesion and neurite outgrowth (By similarity). Interacts with FST3 and MYOC (By similarity).|||Muscle-specific mutant mice show comparable body weight, glucose tolerance test (GTT) and insulin tolerance test (ITT) with control mice. After high fat diet (HFD) feeding and exercise training, control and mutant mice have a similar body weight and liver and muscle tissue weight but daily exercise training improves GTT and ITT values in HFD-fed control mice but not in HFD-fed mutants.|||Phosphorylated by FAM20C in the extracellular medium.|||Proteolytic processing produces the C-terminal NC1 peptide, anastellin.|||Secreted|||Secreted by contracting muscle, induces liver autophagy, a degradative pathway for nutrient mobilization and damage removal, and systemic insulin sensitization via hepatic ITGA5:ITGB1 integrin receptor signaling.|||Serotonylated on Gln residues by TGM2 in response to hypoxia.|||Some lysine residues are oxidized to allysine by LOXL3, promoting fibronectin activation and matrix formation.|||Sulfated.|||extracellular matrix http://togogenome.org/gene/10090:Prkar1b ^@ http://purl.uniprot.org/uniprot/P12849|||http://purl.uniprot.org/uniprot/Q3TY04 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cAMP-dependent kinase regulatory chain family.|||Cell membrane|||Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.|||Membrane|||Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.|||The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. Interacts with PRKX; regulates this cAMP-dependent protein kinase (By similarity). Interacts with smAKAP; this interaction may target PRKAR1B to the plasma membrane (By similarity).|||The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity. http://togogenome.org/gene/10090:Npl ^@ http://purl.uniprot.org/uniprot/Q9DCJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DapA family. NanA subfamily.|||Catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate. It prevents sialic acids from being recycled and returning to the cell surface. Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway.|||Cytoplasm|||Homotetramer. http://togogenome.org/gene/10090:Or9k2b ^@ http://purl.uniprot.org/uniprot/Q8VFU6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Scyl3 ^@ http://purl.uniprot.org/uniprot/Q9DBQ7 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Cytoplasm|||Golgi apparatus|||Interacts with EZR/VIL2 C-terminal domain.|||May be myristoylated; myristoylation may target it to Golgi compartment.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||May play a role in regulating cell adhesion/migration complexes in migrating cells.|||The protein kinase domain is predicted to be catalytically inactive.|||lamellipodium http://togogenome.org/gene/10090:Calm3 ^@ http://purl.uniprot.org/uniprot/P0DP26|||http://purl.uniprot.org/uniprot/P0DP27|||http://purl.uniprot.org/uniprot/P0DP28 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calmodulin family.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.|||Interacts with CEP97, CCP110, MYO1C, TTN/titin and SRY. Interacts with MYO10. Interacts with RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity). Interacts with RYR1 (PubMed:18650434). Interacts with MYO5A (By similarity). Interacts with IQCF1 (PubMed:25380116). Interacts with SYT7 (PubMed:24569478). Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity). Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434). Interacts with PCP4; regulates calmodulin calcium-binding (By similarity). Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (By similarity).|||Interacts with CEP97, CCP110, MYO1C, TTN/titin and SRY. Interacts with MYO10. Interacts with RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity). Interacts with RYR1 (PubMed:18650434). Interacts with MYO5A (PubMed:17151196). Interacts with IQCF1 (PubMed:25380116). Interacts with SYT7 (PubMed:24569478). Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity). Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434). Interacts with PCP4; regulates calmodulin calcium-binding (By similarity). Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (By similarity). Interacts with alpha-synuclein/SNCA (By similarity). Interacts with SLC9A1 in a calcium-dependent manner (By similarity). In the absence of Ca(+2), interacts with GIMAP4 (via IQ domain) (PubMed:16569770). Interacts with SCN8A; the interaction modulates the inactivation rate of SCN8A (PubMed:23942337). Interaction with KIF1A; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility (By similarity). Interacts with KCNN3 (By similarity). Interacts with KCNQ1 (via C-terminus); forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (By similarity). Interacts with PIK3C3; the interaction modulates PIK3C3 kinase activity (By similarity). Interacts with HINT1; interaction increases in the presence of calcium ions (PubMed:31088288). Interacts with HINT3 (PubMed:31088288). Interacts with GARIN2; in mature sperm flagella (PubMed:29025071). Interacts with IQUB (PubMed:36417862). Interacts with SLC26A5 (via STAS domain); this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).|||Phosphorylation results in a decreased activity.|||The N-terminal and C-terminal lobes of CALM bind to the C-terminus of KCNQ1 in a clamp-like conformation. Binding of CALM C-terminus to KCNQ1 is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to KCNQ1 is calcium-dependent and regulates electrophysiological activity of the channel.|||This protein has four functional calcium-binding sites.|||Ubiquitination results in a strongly decreased activity.|||centrosome|||flagellum|||spindle|||spindle pole http://togogenome.org/gene/10090:Mlh3 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VMP7|||http://purl.uniprot.org/uniprot/Q3V1X3|||http://purl.uniprot.org/uniprot/Q68FG1|||http://purl.uniprot.org/uniprot/Q8BZC3 ^@ Similarity ^@ Belongs to the DNA mismatch repair MutL/HexB family. http://togogenome.org/gene/10090:Adal ^@ http://purl.uniprot.org/uniprot/Q80SY6 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.|||Binds 1 zinc ion per subunit.|||Catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotide N(6)-methyl-AMP (N6-mAMP) to produce inositol monophosphate (IMP) and methylamine. Is required for the catabolism of cytosolic N6-mAMP, which is derived from the degradation of mRNA containing N6-methylated adenine (m6A).|||Monomer. http://togogenome.org/gene/10090:Or1e35 ^@ http://purl.uniprot.org/uniprot/Q8VGR3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fgf1 ^@ http://purl.uniprot.org/uniprot/P61148|||http://purl.uniprot.org/uniprot/Q6ZWS1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Cytoplasm|||In the nucleus, phosphorylated by PKC/PRKCD.|||Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGFBP1. Part of a Cu(2+)-dependent multiprotein aggregate containing FGF1, S100A13 and SYT1. Interacts with SYT1. Interacts with S100A13 (By similarity). Interacts with LRRC59 (By similarity). Interacts with CSNKA, CSNKB and FIBP (By similarity). While binding with LRRC59, CSNKA and FIBP seem mutually exclusive, CSNKB and FIBP may cooperatively interact with FGF1. Forms a ternary complex with FGFR1 and ITGAV:ITGB3 and induces the recruitment of PTPN11 to the complex (By similarity).|||Nucleus|||Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1. Can induce angiogenesis.|||Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrins. Its binding to integrins and subsequent ternary complex formation with integrins and FGFR1 are essential for FGF1 signaling.|||Secreted|||cell cortex|||cytosol http://togogenome.org/gene/10090:Dkk1 ^@ http://purl.uniprot.org/uniprot/O54908 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6 (PubMed:18524778). Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity (PubMed:26206087). Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning (PubMed:18505822).|||Belongs to the dickkopf family.|||Expressed in the developing brain, cochlea and limb buds.|||Interacts (via the C-termianl Cys-rich domain) with LRP5 (via beta-propeller regions 3 and 4); the interaction, enhanced by MESD and or KREMEN, antagonizes Wnt-mediated signaling. Interacts with LRP6 (PubMed:18524778). Forms a ternary complex with LRP6 and KREM1. Interacts with KREM1 (By similarity).|||Secreted|||The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.|||Triple knockout mice KREM1/KREM2/DKK1 exhibit enhanced growth of ectopic digits. http://togogenome.org/gene/10090:Chrne ^@ http://purl.uniprot.org/uniprot/P20782|||http://purl.uniprot.org/uniprot/Q5SXG9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Epsilon/CHRNE sub-subfamily.|||Cell membrane|||Membrane|||Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (By similarity).|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Rnf34 ^@ http://purl.uniprot.org/uniprot/Q99KR6 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated (in vitro).|||Cell membrane|||Down-regulated in response to cold exposure.|||E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. May mediate 'Lys-48'-linked polyubiquitination of RIPK1 and its subsequent proteasomal degradation thereby indirectly regulating the tumor necrosis factor-mediated signaling pathway. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. Mediates PPARGC1A proteasomal degradation probably through ubiquitination thereby indirectly regulating the metabolism of brown fat cells (PubMed:22064484). Possibly involved in innate immunity, through 'Lys-48'-linked polyubiquitination of NOD1 and its subsequent proteasomal degradation.|||Endomembrane system|||Interacts with CASP8 and CASP10. Interacts with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2. Interacts (via RING-type zinc finger) with PPARGC1A. Interacts with NOD1.|||Nucleus|||Nucleus speckle|||Proteolytically cleaved by caspases upon induction of apoptosis by TNF.|||The FYVE-type zinc finger domain is required for localization and may confer affinity for cellular compartments enriched in phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate phospholipids.|||The RING-type zinc finger is required for the ubiquitination of target proteins.|||cytosol http://togogenome.org/gene/10090:Pink1 ^@ http://purl.uniprot.org/uniprot/Q99MQ3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated (PubMed:25474007). Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation (By similarity). Autophosphorylation at Ser-227 and Ser-401 is essential for selective recruitment of PRKN to depolarized mitochondria, via PINK1-dependent phosphorylation of ubiquitin and PRKN (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||High levels expressed in testis, lower levels in brain, heart, lung, liver and kidney.|||Interacts with PRKN (By similarity). Interacts with FBXO7 (By similarity). Forms a complex with PRKN and PARK7 (PubMed:19229105). Interacts with NENF (PubMed:31536960).|||Mitochondrial dysfunction (PubMed:18687901, PubMed:20049710, PubMed:32484300). Mice do not show gross structural defects in mitochondria, although the number of larger mitochondria is selectively increased (PubMed:18687901, PubMed:32484300). Mitochondrial respiration is impaired in the striatum, which is rich in dopaminergic terminals, but not in the cerebral cortex in young mice (PubMed:18687901). Mitochondrial respiration activities in the cerebral cortex are decreased in 2 years old mice (PubMed:18687901). Mice show defects in mitochondrial complex I and a decrease in mitochondrial membrane potential (PubMed:20049710). Decreased phosphorylation of Dnm1l in embryonic fibroblasts and in the substantial nigra of 18 month old mice (PubMed:32484300).|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Proteolytically cleaved. In healthy cells, the precursor is continuously imported into the inner mitochondrial membrane (IMM), where it is proteolytically cleaved by mitochondrial-processing peptidase (MPP) and then undergoes further proteolytic cleavage by PARL or AFG3L2 to give rise to the 52 kDa short form. The 52 kDa short form is then released into the cytosol where it rapidly undergoes proteasome-dependent degradation. In unhealthy cells, when cellular stress conditions lead to the loss of mitochondrial membrane potential, mitochondrial import is impaired leading to the precursor accumulating on the outer mitochondrial membrane (OMM). If accumulation at the OMM fails and it is imported into the depolarized mitochondria, it undergoes cleavage by the IMM protease OMA1, promoting its subsequent degradation by the proteasome.|||Serine/threonine-protein kinase which protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as PRKN and DNM1L, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:24652937, PubMed:24784582, PubMed:25474007, PubMed:32484300). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (By similarity). Mediates the translocation and activation of PRKN at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:24652937, PubMed:24784582, PubMed:25474007, PubMed:32484300). At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains at 'Ser-65', the PINK1-phosphorylated polyubiquitin then recruits PRKN from the cytosol to the OMM where PRKN is fully activated by phosphorylation at 'Ser-65' by PINK1 (PubMed:24652937, PubMed:24784582, PubMed:25474007, PubMed:32484300). In damaged mitochondria, mediates the decision between mitophagy or preventing apoptosis by promoting PRKN-dependent poly- or monoubiquitination of VDAC1; polyubiquitination of VDAC1 by PRKN promotes mitophagy, while monoubiquitination of VDAC1 by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (By similarity). When cellular stress results in irreversible mitochondrial damage, functions with PRKN to promote clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:24784582, PubMed:25474007). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by phosphorylating and thus promoting the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (By similarity). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (By similarity). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (PubMed:24652937). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128).|||cytosol http://togogenome.org/gene/10090:B3galt4 ^@ http://purl.uniprot.org/uniprot/A0A068BIS6|||http://purl.uniprot.org/uniprot/Q9Z0F0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Expressed in heart, brain, spleen, kidney, lung and testis.|||First expressed at embryonic day 3. Maintained at high levels between days 4 and 7 and declines thereafter to stabilize at low levels after day 10.|||Golgi apparatus membrane|||Involved in GM1/GD1B/GA1 ganglioside biosynthesis.|||Membrane http://togogenome.org/gene/10090:Tmod4 ^@ http://purl.uniprot.org/uniprot/Q3UN19|||http://purl.uniprot.org/uniprot/Q9JLH8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tropomodulin family.|||Binds to the N-terminus of tropomyosin and to actin.|||Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Or11i1 ^@ http://purl.uniprot.org/uniprot/Q8VFC3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Uxt ^@ http://purl.uniprot.org/uniprot/Q9WTZ0 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UXT family.|||Cytoplasm|||Homohexamer (By similarity). Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (By similarity). Interacts with LRPPRC (By similarity). Interacts with androgen receptor AR (via N-terminus) (By similarity). Interacts with estrogen receptor ESR1; the interaction relocalizes ESR1 to the cytoplasm (By similarity). In the nucleus, interacts specifically with RELA (via RHD domain) and forms a dynamic complex with NF-kappa-B and is recruited to the NF-kappa-B enhanceosome upon stimulation (By similarity). Interacts with MECOM (By similarity). Interacts with URI1 (By similarity).|||Involved in gene transcription regulation. Acts in concert with the corepressor URI1 to regulate androgen receptor AR-mediated transcription. Together with URI1, associates with chromatin to the NKX3-1 promoter region. Negatively regulates the transcriptional activity of the estrogen receptor ESR1 by inducing its translocation into the cytoplasm. May act as nuclear chaperone that facilitates the formation of the NF-kappa-B enhanceosome and thus positively regulates NF-kappa-B transcription activity. Potential component of mitochondrial-associated LRPPRC, a multidomain organizer that potentially integrates mitochondria and the microtubular cytoskeleton with chromosome remodeling. Increasing concentrations of UXT contributes to progressive aggregation of mitochondria and cell death potentially through its association with LRPPRC. Suppresses cell transformation and it might mediate this function by interaction and inhibition of the biological activity of cell proliferation and survival stimulatory factors like MECOM.|||No initiation Met is found in the EST sequence upstream the Met for isoform 1.|||Nucleus|||Part of complex I composed of TNF-alpha receptor, TRADD, TRAF2 and RIPK1 (By similarity). Within the complex, interacts (via TPQE motif) with TRAF2; the interaction prevents the recruitment of FADD and CASP8/caspase 8 to complex I (PubMed:21307340).|||Plays a role in protecting cells against TNF-alpha-induced apoptosis by preventing the recruitment of FADD and caspase 8 to the apoptotic complex I, composed of TRADD, TRAF2 and RIPK1/RIP.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Cstf2 ^@ http://purl.uniprot.org/uniprot/A2AEK1|||http://purl.uniprot.org/uniprot/Q8BIQ5 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in most somatic cell types (at protein level). Highly expressed in testis, except in meiotic spermatocytes.|||Nucleus|||One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. This subunit is directly involved in the binding to pre-mRNAs (By similarity).|||The CSTF complex is composed of CSTF1 (50 kDa subunit), CSTF2 (64 kDa subunit) and CSTF3 (77 kDa subunit). CSTF2 directly interacts with CSTF3, SYMPK and RPO2TC1. Interacts with HSF1 in heat-stressed cells (By similarity). Interacts with CPSF2, CPSF3 and FIP1L1. Interacts with DDX1 (By similarity).|||Up-regulated during the G to S phase transition. http://togogenome.org/gene/10090:Nnat ^@ http://purl.uniprot.org/uniprot/G3UWR4|||http://purl.uniprot.org/uniprot/G3UWR7|||http://purl.uniprot.org/uniprot/Q548P9|||http://purl.uniprot.org/uniprot/Q61979 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Tissue Specificity ^@ Belongs to the neuronatin family.|||Expressed in rhombomeres 3 and 5 during early hindbrain development and in the floor of the foregut pocket. Also expressed in the early Rathke pouch, derived adenohypophysis, and developing inner ear. During later embryogenesis, strongly expressed in the major part of the central and peripheral nervous system.|||Highest in brain and ovary.|||Incorrect N-terminal sequence due to reversal of the first 22 base pairs of the cDNA.|||May participate in the maintenance of segment identity in the hindbrain and pituitary development, and maturation or maintenance of the overall structure of the nervous system. http://togogenome.org/gene/10090:Resf1 ^@ http://purl.uniprot.org/uniprot/Q5DTW7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with SETDB1.|||Nucleus|||Plays a role in the regulation of imprinted gene expression, regulates repressive epigenetic modifications associated with SETDB1. Required for the recruitment or accumulation of SETDB1 to the endogenous retroviruses (ERVs) and maintenance of repressive chromatin configuration, contributing to a subset of the SETDB1-dependent ERV silencing in embryonic stem cells. http://togogenome.org/gene/10090:Aip ^@ http://purl.uniprot.org/uniprot/O08915 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with RET in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex.|||May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting. http://togogenome.org/gene/10090:Drosha ^@ http://purl.uniprot.org/uniprot/Q5HZJ0 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ribonuclease III family.|||Component of the microprocessor complex, or pri-miRNA processing protein complex, which is composed of DROSHA and DGCR8 (By similarity). The microprocessor complex is a heterotrimer; each of the two DROSHA RNase III domains binds one DGCR8 (via C-terminal region) (By similarity). Interacts with SP1 and SNIP1 (By similarity). Interacts with SRRT/ARS2 (PubMed:19632182). Interacts with CPSF3 and ISY1; this interaction is in an RNA dependent manner (PubMed:26255770). Interacts with PUS10; interaction promotes pri-miRNAs processing (By similarity).|||Each RNase III domain binds at least one Mg(2+) or Mn(2+) ion.|||Nucleus|||Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs (PubMed:26255770). Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.|||The 2 RNase III domains form an intramolecular dimer where the domain 1 cuts the 3'strand while the domain 2 cleaves the 5'strand of pri-miRNAs, independently of each other.|||nucleolus http://togogenome.org/gene/10090:Rras2 ^@ http://purl.uniprot.org/uniprot/P62071 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Fatty-acylation at Lys-192, Lys-194; lys-196 and Lys-197 is required for localization to the plasma membrane and activity. Defatty-acylated by SIRT6, affecting its localization to the plasma membrane.|||GTP-binding protein with GTPase activity involved in the regulation of MAPK signaling pathway, thereby controlling multiple cellular processes. Involved in the regulation of MAPK signaling pathway. Regulation of craniofacial development.|||Golgi apparatus membrane|||Interacts with RASSF5.|||May be post-translationally modified by both palmitoylation and polyisoprenylation. http://togogenome.org/gene/10090:St8sia5 ^@ http://purl.uniprot.org/uniprot/P70126|||http://purl.uniprot.org/uniprot/Q3TRR3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||First detected at 14 dpc, expression increases until at least 7 weeks after birth.|||Golgi apparatus membrane|||Highly expressed in brain. Expressed at low levels in other tissues, including liver, testis, lung, placenta and spleen.|||Involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, GP1c and GT3 from GD1a, GT1b, GM1b and GD3 respectively.|||Membrane http://togogenome.org/gene/10090:Elane ^@ http://purl.uniprot.org/uniprot/Q3UP87 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the peptidase S1 family. Elastase subfamily.|||Interacts with NOTCH2NL.|||Mice with a homozygous knockout of this gene are more easily killed by wild-type E.coli, but the knockout has no visible killing effect on E.coli deleted for outer membrane protein A (ompA).|||Serine protease that modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis (By similarity). Capable of killing E.coli; probably digests outer membrane protein A (ompA) in E.coli (PubMed:10947984). http://togogenome.org/gene/10090:Trem1 ^@ http://purl.uniprot.org/uniprot/Q9JKE2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cell surface receptor that plays important roles in innate and adaptive immunity by amplifying inflammatory responses. Upon activation by various ligands such as PGLYRP1, HMGB1 or HSP70, multimerizes and forms a complex with transmembrane adapter TYROBP/DAP12. In turn, initiates a SYK-mediated cascade of tyrosine phosphorylation, activating multiple downstream mediators such as BTK, MAPK1, MAPK3 or phospholipase C-gamma. This cascade promotes the neutrophil- and macrophage-mediated release of pro-inflammatory cytokines and/or chemokines, as well as their migration and thereby amplifies inflammatory responses that are triggered by bacterial and fungal infections (PubMed:23241959, PubMed:27328755). By also promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptor (TLR) and NOD-like receptor engagement, plays a major role in the pathophysiology of acute and chronic inflammatory diseases of different etiologies including septic shock and atherosclerosis (By similarity).|||Deletion mutants do not show any influence of the antiviral T-cell response. However, TREM1 deficiency impairs secretion of CCL2 and TNF-alpha by neutrophils in response to viruses (PubMed:27328755). TREM-1/3-deficient animals have decreased neutrophils in the airway and these neutrophils have a defect in transepithelial migration (PubMed:23241959).|||Monomer (PubMed:15561137). Homomultimer; when activated. Interacts with TYROBP/DAP12. Interacts with TLR4 (By similarity). http://togogenome.org/gene/10090:Edem1 ^@ http://purl.uniprot.org/uniprot/Q925U4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 47 family.|||Endoplasmic reticulum membrane|||Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan-independent manner, probably by forming a complex with SEL1L. It has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2.|||Interacts with DERL2 and DERL3. Binds to SEL1L (By similarity). Interacts with DNAJC10. http://togogenome.org/gene/10090:Prph2 ^@ http://purl.uniprot.org/uniprot/P15499|||http://purl.uniprot.org/uniprot/Q3UWK3 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRPH2/ROM1 family.|||Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure (PubMed:6715580). Required for the maintenance of retinal outer nuclear layer thickness (PubMed:6715580, PubMed:29961824). Required for the correct development and organization of the photoreceptor inner segment (PubMed:6715580).|||Expressed in the retina (at protein level).|||Homodimer; disulfide-linked (PubMed:29961824). Forms a homotetramer (PubMed:10802659). Forms a heterotetramer with ROM1 (PubMed:26406599, PubMed:29961824). Homotetramer and heterotetramer core complexes go on to form higher order complexes by formation of intermolecular disulfide bonds (By similarity). Interacts with MREG (PubMed:17260955). Interacts with STX3 isoform 3B (PubMed:26406599). Interacts with SNAP25 (PubMed:26406599).|||Knockout mice fail to form retinal disk structures, resulting in an absence of the photoreceptor outer segment (PubMed:6715580). At postnatal day 14 the photoreceptor inner segment is stunted and at postnatal day 21 shows disorganization and cell lysis in addition to outer nuclear layer degeneration resulting in a gradual decline in photoreceptors (PubMed:6715580). At postnatal day 21 mice show progressive thinning of the outer plexiform layer and disorganization of the photoreceptor synaptic termini (PubMed:6715580). Adult knockout mice show a reduction in the thickness of the retinal outer nuclear layer, and a decrease in Rom1 protein abundance in the retina (PubMed:29961824).|||Membrane|||Photoreceptor inner segment|||Responsible for retinal degeneration slow (Rds) (PubMed:8530028).|||photoreceptor outer segment http://togogenome.org/gene/10090:Nopchap1 ^@ http://purl.uniprot.org/uniprot/Q9CX66 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Client-loading PAQosome/R2TP complex cofactor that selects NOP58 to promote box C/D small nucleolar ribonucleoprotein (snoRNP) assembly. Acts as a bridge between NOP58 and the R2TP complex via RUVBL1:RUVBL2.|||Interacts with NOP58, RUVBL1 and RUVBL2; the interactions are direct and NOPCHAP1 bridges the association of NOP58 with RUVBL1:RUVBL2 even in absence of snoRNAs. The interactions with RUVBL1 and RUVBL2 are disrupted upon ATP binding.|||Nucleus http://togogenome.org/gene/10090:Defb35 ^@ http://purl.uniprot.org/uniprot/Q8R2I3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Expressed in testis, epididymis (caput, corpus and cauda), kidney and neonatal and adult brain.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Ptpn18 ^@ http://purl.uniprot.org/uniprot/Q61152 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.|||Cytoplasm|||Expressed in the embryo from day 15.5.|||Highest expression in bone marrow. Also expressed in kidney, lung, ovary, spleen, thymus and lymph node.|||Interacts with PSTPIP1.|||May be involved in growth and differentiation of hematopoietic cells.|||Nucleus http://togogenome.org/gene/10090:Ogfod2 ^@ http://purl.uniprot.org/uniprot/Q9CQ04 ^@ Cofactor|||Similarity ^@ Belongs to the OGFOD2 family.|||Binds 1 Fe(2+) ion per subunit. http://togogenome.org/gene/10090:Hcar1 ^@ http://purl.uniprot.org/uniprot/A0A4Y1JWM1|||http://purl.uniprot.org/uniprot/E9PZR8|||http://purl.uniprot.org/uniprot/Q8C131 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Highly expressed in subcutaneous fat and omental fat and detectable in lower levels in brain and many other tissues. High levels detected in epididymal and subcutaneous fat with slightly lower in omental fat, low levels are detected in the brain, skeletal muscle, kidney, liver and the pancreas (at protein level).|||Membrane http://togogenome.org/gene/10090:Nos2 ^@ http://purl.uniprot.org/uniprot/P29477 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOS family.|||Binds 1 FAD.|||Binds 1 FMN.|||By treatment with endotoxins or cytokines. By lipopolysaccharides (LPS) (in vitro). Expression in the liver oscillates in a circadian manner with peak levels occurring during the late night.|||Homodimer (PubMed:10769116, PubMed:11669619). Interacts with NHERF1 (By similarity). Interacts with GAPDH (By similarity). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex (By similarity). Interacts with SPSB1, SPSB2 and SPSB4 (PubMed:20603330). Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4 (By similarity). Forms a complex with ASL, ASS1 and HSP90AA1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.|||Macrophages.|||Not stimulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity.|||Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation.|||Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7503239). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (PubMed:16373578). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (By similarity). Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8 (By similarity).|||Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.|||cytosol http://togogenome.org/gene/10090:Cd1d1 ^@ http://purl.uniprot.org/uniprot/P11609 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.|||Cell membrane|||During protein synthesis and maturation, CD1 family members bind endogenous lipids that are replaced by lipid or glycolipid antigens when the proteins are internalized and pass through endosomes, before trafficking back to the cell surface.|||Endosome membrane|||Expressed on cortical thymocytes, on certain T-cell leukemias, and in various other tissues.|||Heterodimer with B2M (beta-2-microglobulin). Interacts with MHC II and CD74.|||Lysosome membrane|||N-glycosylated. http://togogenome.org/gene/10090:Plekha8 ^@ http://purl.uniprot.org/uniprot/Q80W71 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cargo transport protein that is required for apical transport from the trans-Golgi network (TGN). Transports AQP2 from the trans-Golgi network (TGN) to sites of AQP2 phosphorylation. Mediates the non-vesicular transport of glucosylceramide (GlcCer) from the trans-Golgi network (TGN) to the plasma membrane and plays a pivotal role in the synthesis of complex glycosphingolipids. Binding of both phosphatidylinositol 4-phosphate (PIP) and ARF1 are essential for the GlcCer transfer ability. Also required for primary cilium formation, possibly by being involved in the transport of raft lipids to the apical membrane, and for membrane tubulation (By similarity).|||Homodimer. Interacts with ARF1; the interaction together with phosphatidylinositol 4-phosphate binding is required for FAPP2 GlcCer transfer ability.|||Membrane|||The PH domain of FAPPS binds the small GTPase ARF1 and phosphatidylinositol-4-phosphate (PtdIns4P) with high selectivity, and is required for recruitment of FAPPs to the trans-Golgi network (TGN).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ttc12 ^@ http://purl.uniprot.org/uniprot/Q8BW49 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Cytoplasmic protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. http://togogenome.org/gene/10090:Nox4 ^@ http://purl.uniprot.org/uniprot/B2RSM1|||http://purl.uniprot.org/uniprot/Q9JHI8 ^@ Activity Regulation|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by insulin. Inhibited by diphenylene iodonium (By similarity). Inhibited by plumbagin. Activated by phorbol 12-myristate 13-acetate (PMA).|||Cell membrane|||Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB.|||EXpressed in brain, in all layers of the cerebellum, in pyramidal cells of the Ammon horn and in Purkinje cells (at protein level). Expressed in osteoclasts, leukocytes, kidney, liver and lung.|||Endoplasmic reticulum membrane|||Interacts with, relocalizes and stabilizes CYBA/p22phox. Interacts with TLR4. Interacts with protein disulfide isomerase (By similarity). Interacts with PPP1R15A (By similarity).|||Membrane|||N-glycosylation is required for the function.|||Upon brain ischemia it is up-regulated in ischemic tissues and more specially in neocapillaries (at protein level). Up-regulated upon hypoxia.|||focal adhesion http://togogenome.org/gene/10090:Ptprm ^@ http://purl.uniprot.org/uniprot/P28828|||http://purl.uniprot.org/uniprot/Q68FM4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.|||Cell membrane|||Homodimer.|||Membrane|||Most abundant in lung, less in brain and heart.|||Receptor protein-tyrosine phosphatase that mediates homotypic cell-cell interactions and plays a role in adipogenic differentiation via modulation of p120 catenin/CTNND1 phosphorylation. Promotes CTNND1 dephosphorylation and prevents its cytoplasmic localization where it inhibits SLC2A4 membrane trafficking. In turn, SLC2A4 is directed to the plasma membrane and performs its glucose transporter function. http://togogenome.org/gene/10090:Chuk ^@ http://purl.uniprot.org/uniprot/E9Q605|||http://purl.uniprot.org/uniprot/E9QNL4|||http://purl.uniprot.org/uniprot/Q3TPN9|||http://purl.uniprot.org/uniprot/Q3UDK0|||http://purl.uniprot.org/uniprot/Q8CBT3 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Or51ah3 ^@ http://purl.uniprot.org/uniprot/Q8VGY4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ing1 ^@ http://purl.uniprot.org/uniprot/Q3ULE3|||http://purl.uniprot.org/uniprot/Q9QXV3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ING family.|||Expressed throughout the whole embryo at all stages of development examined. At day 10, highest expression is found in the yolk sac while at day 16 and 18, higher levels are found in inner compartments of bone. In the embryo, highest expression of isoform 1 is found at day 11 while highest expression of isoform 2 is found at day 7.|||In the adult, widely expressed with highest levels in thymus and testis.|||Interacts with H3K4me3 and to a lesser extent with H3K4me2. Isoform 2 interacts with RSL1D1.|||Isoform 1 inhibits p53-dependent transcriptional activation and may function as an oncoprotein. Isoform 2 acts as a negative growth regulator by cooperating with p53 in transcriptional activation of p53-responsive genes and may act as a tumor suppressor.|||Nucleus|||The PHD-type zinc finger mediates the binding to H3K4me3.|||The polybasic region (PBR) is responsive to the binding to phosphoinositides (PtdInsPs), including phosphatidylinositol 5-phosphate (PtdIns(5)P). http://togogenome.org/gene/10090:Vmn1r126 ^@ http://purl.uniprot.org/uniprot/L7N2C8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gas2 ^@ http://purl.uniprot.org/uniprot/P11862 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 11.5 dpc and 13.5 dpc strongly expressed in the soft connective tissue of the face and trunk, and in the invertebral tissues. Low levels are found in brain and neural tube. Low levels are found in 13.5 dpc lung, kidney, eye lens and in vertebral cartilage located cranially. In 11.5 dpc hindlimbs weakly expressed by the mesenchymal cells surrounding the perspective cartilage-forming regions. In 12.5 dpc hindlimbs strongly expressed by cells enveloping the chondrogenic primordia of the digits, metatarsals, tibia, and femur, and the soft connective tissue in the interdigital tissues. In 13.5 dpc hindlimbs expression is maintained in the intergigital tissues located proximally and is found in some chondrocytes in the stylopod and in mesenchymal cells surrounding the cartilage in the autopod and zygopod. In 13.5 dpc forelimb strongly expressed in the pre-hypertrophic and hypertrophic regions of the humerus, radius, and ulna. Expression in hypertrophic chondrocytes is maintained at 14.5 dpc and is not detectable at 15.5 dpc. At day 14.5 dpc also expressed by chondrocytes in the cartilage forming the carpals and tarsals and by mesenchymal cells in the process of condensing to form tendons. In 13.5 dpc hindlimbs expressed in some myoblasts in the proximal myogenic region. In older limbs expression is maintained in the myotubules.|||Belongs to the GAS2 family.|||Cleaved, during apoptosis, on a specific aspartic residue by caspases.|||Down-regulated by mitogens.|||Expressed in most tissues. Highest levels in liver, lung and kidney. In the embryo strongly expressed in regions that undergo extensive apoptosis, such as the intervertebral tissues, the cranofacial mesenchyme and the cartilage of the limbs.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||May play a role in apoptosis by acting as a cell death substrate for caspases. Is cleaved during apoptosis and the cleaved form induces dramatic rearrangements of the actin cytoskeleton and potent changes in the shape of the affected cells. May play a role in chondrocyte proliferation and differentiation, and in limb myogenesis. May be involved in the regulation of the apoptosis in the interdigital tissues of the developing hindlimb. May be involved in the membrane ruffling process.|||Membrane|||Phosphorylated on serine residues during the G0-G1 transition phase.|||stress fiber http://togogenome.org/gene/10090:Ttc7 ^@ http://purl.uniprot.org/uniprot/Q8BGB2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (By similarity). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity).|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2) (By similarity). Interacts with PI4KA, interaction is direct (By similarity). Interacts with EFR3 (EFR3A or EFR3B), interaction is direct (By similarity). Interacts with HYCC (HYCC1 or HYCC2), interaction is direct (By similarity). Association with the PI4K complex is strongly reduced by TMEM150A (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Cyfip2 ^@ http://purl.uniprot.org/uniprot/Q5SQX6|||http://purl.uniprot.org/uniprot/Q6PGK0 ^@ Function|||RNA Editing|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CYFIP family.|||Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Interacts with FMR1, FXR1 and FXR2 (PubMed:11438699). Interacts with FMR1; the interaction occurs in a RNA-dependent manner (By similarity). Interacts with RAC1 (activated form) which causes the complex to dissociate, releasing activated WASF1 (By similarity). The complex can also be activated by NCK1 (By similarity). Interacts with SHANK3; the interaction mediates the association of SHANK3 with the WAVE1 complex (PubMed:24153177). Interacts with TMEM108 (via N-terminus); the interaction associates TMEM108 with the WAVE1 complex (PubMed:27605705).|||Cytoplasm|||Expressed in hippocampus (at protein level).|||Nucleus|||Part of the WAVE1 complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). Involved in T-cell adhesion and p53-dependent induction of apoptosis (By similarity). Does not bind RNA. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (PubMed:27605705).|||Partially edited. Editing appears to be brain-specific.|||perinuclear region|||synaptosome http://togogenome.org/gene/10090:Zzz3 ^@ http://purl.uniprot.org/uniprot/Q6KAQ7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). Interacts via (ZZ-type zinc finger) with histone H3 in a methylation-independent manner and acetylation on 'Lys-4' (H3K4ac) moderately enhances the interaction (By similarity).|||Histone H3 reader that is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation (By similarity). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Adam2 ^@ http://purl.uniprot.org/uniprot/Q60718 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A tripeptide motif (QDE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.|||Expressed in the testis and testicular sperm (at protein level).|||Heterodimer with ADAM1/fertilin subunit alpha.|||Membrane|||Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. Could have a direct role in sperm-zona binding or migration of sperm from the uterus into the oviduct. Interactions with egg membrane could be mediated via binding between its disintegrin-like domain to one or more integrins receptors on the egg. This is a non catalytic metalloprotease-like protein (By similarity).|||The signal and the metalloprotease domain are cleaved during the epididymal maturation of the spermatozoa. http://togogenome.org/gene/10090:Clcnka ^@ http://purl.uniprot.org/uniprot/Q9WUB7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family. CLCNKA subfamily.|||Homodimer (By similarity). Interacts with BSND. Forms heteromers with BSND in the thin ascending limb of Henle.|||Membrane|||Specifically expressed in the kidney. All nephron segments expressing BSND also express CLCNK proreins.|||Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms. May be the basolateral chloride channel mediating net chloride absorption in CTAL cells. http://togogenome.org/gene/10090:B4galnt1 ^@ http://purl.uniprot.org/uniprot/A0A1Z4EAV4|||http://purl.uniprot.org/uniprot/Q09200|||http://purl.uniprot.org/uniprot/Q3UN35 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family.|||Golgi apparatus membrane|||Highest at day 7 of embryonic development after which it declines to its lowest levels at day 11 before increasing again.|||Homodimer; disulfide-linked.|||Involved in the biosynthesis of gangliosides GM2, GD2 and GA2.|||Involved in the biosynthesis of gangliosides GM2, GD2, GT2 and GA2 from GM3, GD3, GT3 and GA3, respectively.|||Membrane|||Most abundant in brain, liver, lung, spleen and testis.|||No visible phenotype, excepting a slight decrease in neural conduction velocity from the tibial nerve to the somatosensory cortex (PubMed:8855236). Mutant mice display impaired motor coordination and balance (PubMed:15953602). Sciatic nerves from over three month old mutant mice show signs of Wallerian degeneration, with redundant myelin, degeneration of myelinated fibers, axon dysmyelination, and an apparent decrease in the diameter of myelinated axons (PubMed:15953602). The distances between neurofilaments in myelinated axons from over 3 month old mice are shorter than normal (PubMed:15953602). Mice are less sensitive to C.botulinum neurotoxin type C (BoNT/C), C.botulinum neurotoxin type D (BoNT/D, botD) and C.botulinum neurotoxin type F (BoNT/F, botF) (PubMed:21483489). http://togogenome.org/gene/10090:H2-M1 ^@ http://purl.uniprot.org/uniprot/F7CXU4|||http://purl.uniprot.org/uniprot/Q31200|||http://purl.uniprot.org/uniprot/Q85ZX2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Or6c75 ^@ http://purl.uniprot.org/uniprot/Q8VGJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnh3 ^@ http://purl.uniprot.org/uniprot/Q9WVJ0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.2/KCNH3 sub-subfamily.|||Detected in brain, but not in other tissues.|||Membrane|||Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.|||The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Cyb561d1 ^@ http://purl.uniprot.org/uniprot/A2AE42 ^@ Cofactor|||Function|||Subcellular Location Annotation ^@ Binds 2 heme b groups non-covalently.|||Membrane|||Probable transmembrane reductase that may use ascorbate as an electron donor and transfer electrons across membranes to reduce monodehydro-L-ascorbate radical and iron cations Fe(3+) in another cellular compartment. http://togogenome.org/gene/10090:Pwwp2a ^@ http://purl.uniprot.org/uniprot/Q69Z61 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes (PubMed:30228260, PubMed:33235983). Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z (By similarity). Plays a role in facilitating transcriptional elongation and repression of spurious transcription initiation through regulation of histone acetylation (PubMed:30228260, PubMed:33235983). Essential for proper mitosis progression (By similarity).|||Component of a MTA1-specific subcomplex of the NuRD complex (M1HR), which is composed of PWWP2A, MTA1/2, HDAC1/2, and RBBP4/7 but does not contain CHD4 and MBD3 (By similarity). Interacts with MTA1; the interaction mediates the association of PWWP2A with the M1HR complex (By similarity). Interacts with H2A.Z/H2AZ1 (By similarity). Interacts (via PWWP domain) with histone H3 trimethylated at 'Lys-36' (H3K36me3) (By similarity). Does not interact with CHD4 and MBD3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gxylt2 ^@ http://purl.uniprot.org/uniprot/Q810K9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 8 family.|||Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.|||Membrane http://togogenome.org/gene/10090:Chfr ^@ http://purl.uniprot.org/uniprot/Q810L3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated; may regulate its cellular level.|||Belongs to the CHFR family.|||E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. Probably involved in signaling the presence of mitotic stress caused by microtubule poisons by mediating the 'Lys-48'-linked ubiquitination of target proteins, leading to their degradation by the proteasome. Promotes the ubiquitination and subsequent degradation of AURKA and PLK1. Probably acts as a tumor suppressor, possibly by mediating the polyubiquitination of HDAC1, leading to its degradation. May also promote the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation, but are rather involved in signaling cellular stress (By similarity).|||Interacts with HDAC1 and HDAC2. Interacts with PML (with sumoylated form of PML).|||Mice are viable and have no obvious developmental defects. They are however cancer-prone and develop spontaneous tumors. They also display increased skin tumor incidence after treatment with dimethylbenz(a)anthracene.|||PML body|||Phosphorylated by PKB. Phosphorylation may affect its E3 ligase activity.|||Poly-ADP-ribosylated. In addition to binding non covalently poly(ADP-ribose) via its PBZ-type zinc finger, the protein is also covalently poly-ADP-ribosylated by PARP1.|||The FHA domain plays a key role in the anti-proliferative properties of the protein and is involved in initiating a cell cycle arrest at G2/M. The FHA domain may be required to interact with phosphorylated proteins.|||The PBZ-type zinc finger (also named CYR) mediates non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and is required for its function in antephase checkpoint. http://togogenome.org/gene/10090:Atp6v0d2 ^@ http://purl.uniprot.org/uniprot/Q80SY3 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase V0D/AC39 subunit family.|||Predominantly expressed in the kidney. Also expressed in the lung, testis, skeletal muscle and heart. Upr-egulated during osteoclast differentiation and is most abundant in mature osteoclasts.|||Strongly expressed at day 7 followed by a disappearance and a gradual recovery to original levels by day 17.|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). May play a role in coupling of proton transport and ATP hydrolysis (PubMed:12963731). Regulator of osteoclast fusion and bone formation (PubMed:17128270).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR. http://togogenome.org/gene/10090:Ccdc136 ^@ http://purl.uniprot.org/uniprot/Q3TVA9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Increased in an age-dependent manner from postnatal 3 to 8 weeks.|||Males are infertile, due to severe defect of disrupting acrosome formation.|||May play a role in acrosome formation in spermatogenesis and in fertilization.|||Present at high level in testis (at protein level).|||acrosome membrane http://togogenome.org/gene/10090:Ppp1r26 ^@ http://purl.uniprot.org/uniprot/Q6A025 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes. May positively regulate cell proliferation.|||Interacts with UTP20 and PPP1CA.|||Nude mice injected with Ppp1r26-expressing cells develop tumors within 2 weeks.|||nucleolus http://togogenome.org/gene/10090:Galnt6 ^@ http://purl.uniprot.org/uniprot/Q8C7U7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. May participate in synthesis of oncofetal fibronectin. Has activity toward Muc1a, Muc2, EA2 and fibronectin peptides (By similarity).|||Golgi apparatus membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Or5d14 ^@ http://purl.uniprot.org/uniprot/Q7TR28 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gabrg2 ^@ http://purl.uniprot.org/uniprot/P22723 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by benzodiazepines (By similarity). Activated by pentobarbitol (By similarity). Inhibited by the antagonist bicuculline (By similarity). Inhibited by zinc ions (By similarity).|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG2 sub-subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Expressed in brain neurons (at protein level).|||Glycosylated.|||Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:18281286). Interacts with GABARAP (By similarity). Interacts with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (PubMed:28978485, PubMed:29742426). Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (PubMed:31601770).|||Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta2/gamma2 receptor, alpha2/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity whereas the alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (PubMed:27129275). Functions also as histamine receptor and mediates cellular responses to histamine (PubMed:18281286).|||Palmitoylated by ZDHHC3/GODZ; required for the accumulation of GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic synapses.|||Postsynaptic cell membrane|||The extracellular domain contributes to synaptic contact formation.|||This subunit carries the benzodiazepine binding site.|||dendrite http://togogenome.org/gene/10090:Scin ^@ http://purl.uniprot.org/uniprot/Q60604 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the villin/gelsolin family.|||Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane (PubMed:9671468). Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2) (By similarity). In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+) (PubMed:9671468). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles (By similarity). Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts (PubMed:25275604, PubMed:25681458). Regulates chondrocyte proliferation and differentiation (By similarity). Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways (By similarity).|||Expression is induced during osteoclastogenesis.|||Fails to nucleate actin polymerization, although it severs and caps actin filaments in a Ca(2+)-dependent manner.|||Knockdown in bone marrow monocytes protect mice from bone resorption in periodontal disease model.|||Ubiquitous. Highly expressed in mature osteoclasts (at protein level) (PubMed:25275604). Isoform 2 is expressed in blood cells (PubMed:9671468).|||cytoskeleton|||podosome http://togogenome.org/gene/10090:Pde8b ^@ http://purl.uniprot.org/uniprot/E9PX38|||http://purl.uniprot.org/uniprot/E9PXX4|||http://purl.uniprot.org/uniprot/E9PYP0|||http://purl.uniprot.org/uniprot/E9Q8J6|||http://purl.uniprot.org/uniprot/Q8BI47 ^@ Cofactor|||Similarity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. http://togogenome.org/gene/10090:B4galt7 ^@ http://purl.uniprot.org/uniprot/Q3TAW1|||http://purl.uniprot.org/uniprot/Q8R087 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 7 family.|||Golgi apparatus membrane|||Golgi stack membrane|||Membrane|||Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts.|||Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids. http://togogenome.org/gene/10090:Or1ak2 ^@ http://purl.uniprot.org/uniprot/Q8VFP5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:H2bw2 ^@ http://purl.uniprot.org/uniprot/Q9DAB5 ^@ Similarity ^@ Belongs to the histone H2B family. http://togogenome.org/gene/10090:Kcnip4 ^@ http://purl.uniprot.org/uniprot/Q6PHZ8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the recoverin family.|||Cell membrane|||Component of heteromultimeric potassium channels (PubMed:19713751, PubMed:20943905). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). Interacts with the C-terminus of PSEN2 and probably PSEN1 (By similarity). Interacts with KCND2 and KCND3.|||Cytoplasm|||Expressed in brain. Highly expressed by neurons in layers II-IV of cortex and in hippocampus, thalamus and the Purkinje cell layer of the cerebellum.|||Peroxisome|||Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels, such as KCND2/Kv4.2 and KCND3/Kv4.3 (PubMed:19109250). Modulates channel expression at the cell membrane, gating characteristics, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner.|||The KIS (K-channel inactivation suppressor) domain is required for converting A-type Kv4 current to a slowly inactivating delayed rectifier potassium current. http://togogenome.org/gene/10090:Tyw1 ^@ http://purl.uniprot.org/uniprot/Q8BJM7 ^@ Cofactor|||Function|||Sequence Caution|||Similarity ^@ Belongs to the TYW1 family.|||Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||Probable cloning artifact.|||Probable component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the condensation of N-methylguanine with 2 carbon atoms from pyruvate to form the tricyclic 4-demethylwyosine, an intermediate in wybutosine biosynthesis (By similarity). http://togogenome.org/gene/10090:Slc11a1 ^@ http://purl.uniprot.org/uniprot/P41251 ^@ Caution|||Function|||Induction|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NRAMP family.|||Glycosylated.|||In response to lymphokine, such as IFNG, or bacterial products, such as LPS (PubMed:7665187, PubMed:9730978). Induced in macrophages at early stages of infection (PubMed:7665187).|||Late endosome membrane|||Lysosome membrane|||Macrophage-specific antiporter that fluxes metal ions in either direction against a proton gradient. Localized to late endosomal lysosomal membranes, delivers bivalent cations from the cytosol into these acidic compartments where they may directly affect antimicrobial activity. Involved in iron metabolism and host natural resistance to infection with intracellular parasites. Pathogen resistance involves sequestration of Fe(2+) and Mn(2+), cofactors of both prokaryotic and eukaryotic catalases and superoxide dismutases, not only to protect the macrophage against its own generation of reactive oxygen species, but to deny the cations to the pathogen for synthesis of its protective enzymes.|||Macrophages; spleen and liver.|||The variant Asp-169 displayed in the entry is the variant found in the inbred strains C57BL/6J and BALB/cJ and may be expressed at very low levels in its mature form. In inbred strains, the susceptibility to infection with unrelated intracellular parasites, such as Mycobacterium bovis, Salmonella typhimurium and Leishmania donovani is associated with the single glycine-to-aspartic acid substitution at position 169 (G169D) in the predicted transmembrane domain 4. The conserved and resistant Gly-169 variant show the proper transporter activity described. However the variant Asp-169 shows an altered glycosylated pattern and seems to prevent proper maturation of the protein, resulting in its rapid degradation. The expression of the mature form of variant Asp-169 is strongly decreased in late endosome/lysosome membranes leading to a reduced phagosome-lysosome fusion in macrophages after infection.|||Variant Asp-169 is displayed in the entry because it is the variant found in the inbred strains C57BL/6J and BALB/cJ and even if it seems to not be expressed in its mature form. In inbred strains, the susceptibility to infection with unrelated intracellular parasites, such as Mycobacterium bovis, Salmonella typhimurium and Leishmania donovani is associated with the single glycine-to-aspartic acid substitution at position 169 (G169D) in the predicted transmembrane domain 4. The conserved and resistant Gly-169 variant show the proper transporter activity described in the function and is highly induced in response to lymphokine, such as IFNG, or bacterial products, such as LPS. However the variant Asp-169 shows an altered glycosylated pattern and seems to prevent proper maturation of the protein, resulting in its rapid degradation. The expression of the mature form of variant Asp-169 is strongly decreased in late endosome/lysosome membranes leading to a reduced phagosome-lysosome fusion in macrophages after infection. http://togogenome.org/gene/10090:Mup13 ^@ http://purl.uniprot.org/uniprot/A2CEK6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Bloc1s3 ^@ http://purl.uniprot.org/uniprot/Q5U5M8 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BLOC1S3 family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking.|||Cytoplasm|||Defects in Bloc1s3 are the cause of the reduced pigmentation (rp) mutation phenotype, a mouse model for human Hermansky-Pudlak syndrome (HPS). Rp mice are characterized by abnormal melanosomes and display altered expression levels of the proteins of the BLOC-1 complex.|||Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts directly with BLOC1S2 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. Interacts with BLOC1S4, BLOC1S5 and BLOC1S6.|||Phosphorylated.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Krt35 ^@ http://purl.uniprot.org/uniprot/Q497I4 ^@ Miscellaneous|||Similarity ^@ Belongs to the intermediate filament family.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:AU018091 ^@ http://purl.uniprot.org/uniprot/E9PWS4|||http://purl.uniprot.org/uniprot/Q0PDJ1|||http://purl.uniprot.org/uniprot/Q66JW0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H2ac24 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Or14c43 ^@ http://purl.uniprot.org/uniprot/Q7TS05 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ugt2a2 ^@ http://purl.uniprot.org/uniprot/Q6PDD0 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane|||UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous estrogen hormone estradiol. Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption. Potential role in detoxification of toxic waste compounds in the amniotic fluid before birth, and air-born chemical after birth.|||UGT2A2 isoform is part of the UGT2A complex locus which displays alternative use of promoters and exons. The locus is defined by 2 alternative promoters resulting in 2 fonctionally active polypeptides UGT2A1 and UGT2A2. Alternative splicing of exons results in additional isoforms for each protein class. http://togogenome.org/gene/10090:H2al1n ^@ http://purl.uniprot.org/uniprot/Q497L1 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Carhsp1 ^@ http://purl.uniprot.org/uniprot/Q9CR86 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds mRNA and regulates the stability of target mRNA.|||Can be phosphorylated by DYRK2 (in vitro). Dephosphorylated by calcineurin in a Ca(2+) dependent manner (By similarity).|||Cytoplasm|||Cytoplasmic granule|||Homodimer. Interacts with STYX (By similarity).|||P-body http://togogenome.org/gene/10090:Ncoa3 ^@ http://purl.uniprot.org/uniprot/A5D6Q2|||http://purl.uniprot.org/uniprot/Q05BA5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SRC/p160 nuclear receptor coactivator family.|||Nucleus http://togogenome.org/gene/10090:Wrn ^@ http://purl.uniprot.org/uniprot/O09053|||http://purl.uniprot.org/uniprot/Q3TB25 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the helicase family. RecQ subfamily.|||Binds 2 magnesium ions per subunit. Has high activity with manganese and zinc ions (in vitro).|||Chromosome|||Expressed ubiquitously in most organs at a low level, highly expressed in testis, ovary and spleen.|||Monomer, and homooligomer. May exist as homodimer, homotrimer, homotetramer and/or homohexamer. Homotetramer, or homohexamer, when bound to DNA (By similarity). Interacts via its N-terminal domain with WRNIP1 (PubMed:11301316). Interacts with EXO1, PCNA and SUPV3L1. Interacts with PML (isoform PML-4) (By similarity). Interacts (via KBM motif) with XRCC5 and XRCC6; promoting recruitment to DNA damage sites (By similarity). Interacts with RECQL5; this interaction stimulates WRN helicase activity on DNA fork duplexes (By similarity).|||Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity). Plays a role in double-strand break repair after gamma-irradiation (By similarity).|||Nucleus|||Phosphorylated by PRKDC.|||The KBM 2 (Ku-binding motif 2) and XLM (XLF-like motif) mediate cooperative interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites.|||Zinc ions stimulate the exonuclease activity.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Ccdc181 ^@ http://purl.uniprot.org/uniprot/Q80ZU5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC181 family.|||Homodimer (PubMed:28283191). Interacts with HOOK1 (PubMed:28283191). Interacts with HOOK2 (PubMed:28283191). Interacts with HOOK3 (PubMed:28283191).|||In testis, expressed at low level until day 20, when round spermatids appear for the first time. After day 20, a sharp and constant increase of expression is observed.|||Microtubule-binding protein that localizes to the microtubular manchette of elongating spermatids.|||Predominantly expressed in testis (PubMed:28283191). Expressed at lower level in brain, eye, trachea and lung (PubMed:28283191). Barely expressed in tongue, heart, liver, kidney, spleen and muscle (PubMed:28283191). Present at high level in elongating spermatids, whereas lower levels are observed in round spermatids (at protein level) (PubMed:28283191).|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Tpi1 ^@ http://purl.uniprot.org/uniprot/P17751 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the triosephosphate isomerase family.|||Cytoplasm|||Homodimer.|||It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids.|||Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis. http://togogenome.org/gene/10090:Gm906 ^@ http://purl.uniprot.org/uniprot/Q3V0M1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Arl8b ^@ http://purl.uniprot.org/uniprot/Q9CQW2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) During infection, murine coronavirus (MHV) and the chaperone HSPA5/GRP78 are co-released through ARL8B-dependent lysosomal exocytic pathway for unconventional egress.|||Belongs to the small GTPase superfamily. Arf family.|||Cytolytic granule membrane|||Interacts with tubulin. Interacts with BORCS5; recruits ARL8B to lysosomes. Interacts with VPS41; the interaction mediates the recruitment of the HOPS complex to lysosomes. Interacts (GTP-bound form) with PLEKHM2 (via RUN domain); the interaction is required to recruit the motor protein kinesin-1 on lysosomes. Interacts (GTP-bound form) with PLEKHM1 (via RUN domain); the interaction is required for PLEKHM1 localization to lysosomes and for ARL8B function in delivery and degradation of endocytic and autophagic cargo in lysosomes. PLEKHM1 and PLEKHM2 compete for interaction with ARL8B.|||Late endosome membrane|||Lysosome membrane|||Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of lysosomal positioning which is important for nutrient sensing, natural killer cell-mediated cytotoxicity and antigen presentation (PubMed:33157038, PubMed:30174114). Along with its effectors, orchestrates lysosomal transport and fusion. Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic granule exocytosis. Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (By similarity). In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function (PubMed:30174114). Also acts as a regulator of endosome to lysosome trafficking pathways of special significance for host defense. Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in functional assembly of the HOPS complex on lysosomal membranes. Plays an important role in cargo delivery to lysosomes for antigen presentation and microbial killing. Directs the intersection of CD1d with lipid antigens in lysosomes, and plays a role in intersecting phagosomes with lysosomes to generate phagolysosomes that kill microbes (PubMed:21802320). Involved in the process of MHC II presentation. Regulates the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes allowing the fusion of late endosomes to lysosomes (PubMed:25637027). May play a role in chromosome segregation (By similarity).|||Synapse|||Ubiquitinated at Lys-141 by RNF167, leading to its degradation.|||axon|||spindle http://togogenome.org/gene/10090:Penk ^@ http://purl.uniprot.org/uniprot/P22005|||http://purl.uniprot.org/uniprot/Q3UXY8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the opioid neuropeptide precursor family.|||Highest expression in late pachytene spermatocytes and postmeiotic round spermatids.|||Increases glutamate release in the striatum and decreases GABA concentration in the striatum.|||Increases glutamate release in the striatum.|||Met-enkephalin-Arg-Phe neuropeptide acts as a strong ligand of Mu-type opioid receptor OPRM1 (PubMed:6933569, PubMed:35201898). Met-enkephalin-Arg-Phe-binding to OPRM1 in the nucleus accumbens of the brain increases activation of OPRM1, leading to long-term synaptic depression of glutamate release (PubMed:35201898).|||Neuropeptide that competes with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.|||Probably cleaved by ACE.|||Processed and degraded by ACE.|||Processed by ACE to generate Met-enkephalin in the nucleus accumbens of the brain.|||Proenkephalin-A is cleaved by CTSL to generate Met-enkephalin.|||Secreted|||Spermatogenic and somatic cells.|||The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing.|||chromaffin granule lumen http://togogenome.org/gene/10090:Ndufc1 ^@ http://purl.uniprot.org/uniprot/Q9CQY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFC1 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lancl3 ^@ http://purl.uniprot.org/uniprot/Q8CD19 ^@ Similarity ^@ Belongs to the LanC-like protein family. http://togogenome.org/gene/10090:Anapc4 ^@ http://purl.uniprot.org/uniprot/Q3TM92|||http://purl.uniprot.org/uniprot/Q91W96 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APC4 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Nucleus|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. In the context of the APC/C complex, directly interacts with UBE2S. Interacts with FBXO43. http://togogenome.org/gene/10090:Prps1l1 ^@ http://purl.uniprot.org/uniprot/Q8C5R8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ribose-phosphate pyrophosphokinase family.|||Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.|||Homodimer. The active form is probably a hexamer composed of 3 homodimers. http://togogenome.org/gene/10090:Socs3 ^@ http://purl.uniprot.org/uniprot/O35718 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subunit|||Tissue Specificity ^@ By a subset of cytokines including EPO, leptin, LIF, IL-2, IL-3, IL-4, IGF1, growth hormone and prolactin.|||In the developing brain, expressed at low levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8. In the cortex, first expressed uniformly in all cells at 14 dpc. Not expressed in the retina. Highly expressed in fetal liver progenitors at 12.5 dpc.|||Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and JAK2. Binding to JAK2 is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK2 JH1 domain (By similarity). Binds specific activated tyrosine residues of the leptin, EPO, IL12, GSCF and gp130 receptors (PubMed:10882725). Interaction with CSNK1E stabilizes SOCS3 protein (By similarity). Component of the probable ECS(SOCS3) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, elongin BC complex and SOCS3 (By similarity). Interacts with CUL5, RNF7, ELOB and ELOC (By similarity). Interacts with FGFR3 (By similarity). Interacts with INSR (PubMed:10821852). Interacts with BCL10; this interaction may interfere with BCL10-binding with PELI2 (PubMed:15213237). Interacts with NOD2 (via CARD domain); the interaction promotes NOD2 degradation (PubMed:23019338).|||Low expression in lung, spleen and thymus. Expressed in Th2 but not TH1 cells.|||Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.|||SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors (PubMed:10821852, PubMed:12754505, PubMed:9889194). Binding to JAK2 inhibits its kinase activity and regulates IL6 signaling (PubMed:12754505, PubMed:9889194). Suppresses fetal liver erythropoiesis (PubMed:10490101). Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells (PubMed:12847520). Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).|||The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Krt81 ^@ http://purl.uniprot.org/uniprot/Q9ERE2 ^@ Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in dorsal skin.|||Heterotetramer of two type I and two type II keratins.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Armc9 ^@ http://purl.uniprot.org/uniprot/Q9D2I5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with TOGARAM1, CCDC66, CEP104, CSPP1 and CEP290.|||Involved in ciliogenesis (By similarity). It is required for appropriate acetylation and polyglutamylation of ciliary microtubules, and regulation of cilium length (By similarity). Acts as a positive regulator of hedgehog (Hh) signaling (PubMed:29459677). May participate in the trafficking and/or retention of GLI2 and GLI3 proteins at the ciliary tip (PubMed:29459677).|||centriole|||cilium|||cilium basal body http://togogenome.org/gene/10090:Vmn2r75 ^@ http://purl.uniprot.org/uniprot/G5E8Z7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or10j5 ^@ http://purl.uniprot.org/uniprot/Q62007 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the olfactory epithelium as well as in the testis (PubMed:8619840). Expressed in round spermatids during stages VI-VIII of spermatogenesis (PubMed:15522887).|||Olfactory receptor. Activated by the synthetic floral odorant, lyral, and by alpha-cedrene, a sesquiterpene constituent of cedarwood oil (PubMed:25791473, PubMed:28842679, PubMed:10097159). Its activation increases intracellular Ca(2+) (PubMed:25791473, PubMed:28842679, PubMed:10097159, PubMed:15522887). Acts as a key regulator of myogenesis through its actions on cell migration and adhesion by activating the Ca(2+)-dependent AKT signal transduction pathway (PubMed:19922870). Acts also as a regulator of angiogenesis (PubMed:25791473). Moreover, plays a role in the regulation of lipid accumulation in hepatocytes via the cAMP-PKA pathway (PubMed:28842679). Involved in sperm chemotaxis and motility (PubMed:15522887).|||Up-regulated during myogenesis in vitro and muscle regeneration in vivo. http://togogenome.org/gene/10090:Mucl2 ^@ http://purl.uniprot.org/uniprot/P02815 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in submandibular gland and lacrimal gland. Not detected in other tissues.|||extracellular space http://togogenome.org/gene/10090:Mrpl9 ^@ http://purl.uniprot.org/uniprot/Q14B21|||http://purl.uniprot.org/uniprot/Q99N94 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL9 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Gnai2 ^@ http://purl.uniprot.org/uniprot/P08752 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||Cell membrane|||Cytoplasm|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. In this context, interacts with GNB2 (By similarity). Interacts with UNC5B (By similarity). Interacts with GPSM1 (By similarity). Interacts with RGS12 and RGS14 (By similarity). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif); the interaction leads to activation of GNAI3 (By similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif) (By similarity). Interacts (inactive GDP-bound form) with CCDC8A/GIV (via GBA motif) (By similarity). Interacts with CXCR1 and CXCR2 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division.|||Membrane|||centrosome http://togogenome.org/gene/10090:Zfyve28 ^@ http://purl.uniprot.org/uniprot/Q6ZPK7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lst-2 family.|||Early endosome membrane|||Enriched in brain (at protein level).|||Interacts with TRIM3.|||Monoubiquitination at Lys-87 prevents binding to phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes.|||Negative regulator of epidermal growth factor receptor (EGFR) signaling. Acts by promoting EGFR degradation in endosomes when not monoubiquitinated (By similarity).|||The FYVE-type zinc finger mediates the interaction with phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes when not monoubiquitinated at Lys-87.|||cytosol http://togogenome.org/gene/10090:Arhgap42 ^@ http://purl.uniprot.org/uniprot/B2RQE8 ^@ Function|||Tissue Specificity ^@ Highly and selectively expressed in smooth muscle cells.|||May influence blood pressure by functioning as a GTPase-activating protein for RHOA in vascular smooth muscle. http://togogenome.org/gene/10090:Cept1 ^@ http://purl.uniprot.org/uniprot/Q8BGS7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CDP-alcohol phosphatidyltransferase class-I family.|||Catalyzes both phosphatidylcholine and phosphatidylethanolamine biosynthesis from CDP-choline and CDP-ethanolamine, respectively. Involved in protein-dependent process of phospholipid transport to distribute phosphatidyl choline to the lumenal surface. Has a higher cholinephosphotransferase activity than ethanolaminephosphotransferase activity.|||Endoplasmic reticulum membrane|||Nucleus membrane http://togogenome.org/gene/10090:Ttll10 ^@ http://purl.uniprot.org/uniprot/A4Q9F3 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Gln-307 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in testis (PubMed:17499049). Expressed in brain, heart, kidney, liver, lung, muscle and trachea (PubMed:17499049).|||Polyglycylase which modifies both tubulin and non-tubulin proteins, generating polyglycine side chains of variable lengths on the gamma-carboxyl groups of specific glutamate residues of target proteins (PubMed:19524510, PubMed:18331838, PubMed:19427864). Involved in the elongation step rather than the initiation step of the polyglycylation reaction (PubMed:19524510, PubMed:18331838, PubMed:19427864). Polyglycylates alpha-tubulin and beta-tubulin (PubMed:19524510, PubMed:19427864). Polyglycylates non-tubulin proteins such as nucleosome assembly protein NAP1 (PubMed:18331838).|||cilium|||cilium axoneme|||cytoskeleton http://togogenome.org/gene/10090:C1rb ^@ http://purl.uniprot.org/uniprot/Q8CFG9 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains, each of which is activated by cleavage into two chains, A and B, connected by disulfide bonds (By similarity).|||C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.|||Specifically expressed in male reproductive tissues.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Acnat1 ^@ http://purl.uniprot.org/uniprot/A2AKK5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acyltransferase which efficiently conjugates very long-chain and long-chain fatty acids to taurine (PubMed:17116739). Shows no conjugation activity in the presence of glycine (PubMed:17116739).|||Belongs to the C/M/P thioester hydrolase family.|||Expressed mainly in liver and kidney with low levels in adrenal and little or no expression in other tissues.|||Peroxisome http://togogenome.org/gene/10090:Rfxank ^@ http://purl.uniprot.org/uniprot/Q9Z205 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator/CIITA. May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters (By similarity). May also potentiate the activation of RAF1 (PubMed:10329666).|||Cytoplasm|||Expressed primarily in thymus, lung and testis.|||Forms homodimers (PubMed:10329666). The RFX heterotetrameric complex consists of 2 molecules of RFX5 and one each of RFXAP and RFX-B/RFXANK; with each subunit representing a separate complementation group. Interacts (via ankyrin repeats) with RFX5 (via PxLPxI/L motif); the interaction is direct. RFX forms cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX associates with CIITA to form an active transcriptional complex (By similarity). Interacts with RAF1 (PubMed:10329666). Interacts with RFX7 (By similarity).|||Interacts with RAF-1 via its C-terminal ankyrin repeat domain. The same domain also mediates its homodimerization (PubMed:10329666). The third ankyrin repeat is required for association with the two other RFX subunits; RFX5 and RFXAP. The three central ANK repeats mediate binding to the PxLPxI/L motif of RFX5 (By similarity).|||Nucleus|||Phosphorylated by RAF1. http://togogenome.org/gene/10090:Fbxl15 ^@ http://purl.uniprot.org/uniprot/Q91W61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FBXL15 family.|||Cytoplasm|||Expressed in heart, liver, spleen, bone, muscle, brain and kidney (at protein level).|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL15) composed of CUL1, SKP1, RBX1 and FBXL15.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of SMURF1, thereby acting as a positive regulator of the BMP signaling pathway. Required for dorsal/ventral pattern formation and bone mass maintenance. Also mediates ubiquitination of SMURF2 and WWP2 (By similarity). http://togogenome.org/gene/10090:Nfyc ^@ http://purl.uniprot.org/uniprot/P70353 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NFYC/HAP5 subunit family.|||Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.|||Heterotrimeric transcription factor composed of three components, NF-YA, NF-YB and NF-YC. NF-YB and NF-YC must interact and dimerize for NF-YA association and DNA binding (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ar ^@ http://purl.uniprot.org/uniprot/P19091 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Binds DNA as a homodimer. Part of a ternary complex containing AR, EFCAB6/DJBP and PARK7. Interacts with HIPK3 and NR0B2 in the presence of androgen. The ligand binding domain interacts with KAT7/HBO1 in the presence of dihydrotestosterone. Interacts with EFCAB6/DJBP, PQBP1, RANBP9, SPDEF, SRA1, TGFB1I1, ZNF318 and RREB1. The AR N-terminal poly-Gln region binds Ran resulting in enhancement of AR-mediated transactivation. Ran-binding decreases as the poly-Gln length increases. Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity. Interacts with RBAK. Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3, NCOA4 and MAGEA11. Interacts with HIP1 (via coiled coil domain). Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts with MACROD1 (via macro domain) (By similarity). Interacts (via ligand-binding domain) with TRIM68. Interacts with TNK2. Interacts with USP26. Interacts with RNF6. Interacts (regulated by RNF6 probably through polyubiquitination) with RNF14; regulates AR transcriptional activity. Interacts with PRMT2 and TRIM24. Interacts with RACK1. Interacts with RANBP10; this interaction enhances hormone-induced AR transcriptional activity. Interacts with PRPF6 in a hormone-independent way; this interaction enhances hormone-induced AR transcriptional activity. Interacts with STK4/MST1. Interacts with ZIPK/DAPK3. Interacts with LPXN. Interacts with MAK. Part of a complex containing AR, MAK and NCOA3. Interacts with CRY1 (PubMed:22170608, PubMed:28751364). Interacts with CCAR1 and GATA2 (By similarity). Interacts with BUD31 (By similarity). Interacts with ARID4A (PubMed:23487765). Interacts with ARID4B (PubMed:23487765). Interacts (via NR LBD domain) with ZBTB7A; the interaction is direct and androgen-dependent (By similarity). Interacts with NCOR1 (By similarity). Interacts with NCOR2 (By similarity). Interacts with CRY2 in a ligand-dependent manner (PubMed:28751364).|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins. Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain (By similarity).|||Cytoplasm|||In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.|||Nucleus|||Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation (By similarity).|||Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-514 is one of the major phosphorylation sites and an increase in phosphorylation and Src kinase activity is associated with prostate cancer progression (By similarity). Phosphorylation by TNK2 enhances the DNA-binding and transcriptional activity. Phosphorylation at Ser-61 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR-mediated transcription inhibition (By similarity).|||Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.|||Sumoylated on Lys-381 (major) and Lys-500 (By similarity). Ubiquitinated. Deubiquitinated by USP26 (By similarity). 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity (By similarity).|||Transcriptional activity is enhanced by binding to RANBP9. http://togogenome.org/gene/10090:Cts8 ^@ http://purl.uniprot.org/uniprot/Q9JI81 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Detected from 5.5 dpc in parietal trophoblast giant cells (PubMed:18776147, PubMed:10885754). Detected at 8.5 dpc in placenta, and shows increased expression level from 13.5 to 19.5 dpc (PubMed:11829493).|||Endosome|||Expressed in placenta (PubMed:11829493, PubMed:10885754, PubMed:18776147). Highly expressed in a subset of trophoblast giant cells in the parietal yolk sac and at the outside of the ectoplacental cone (PubMed:10885754). Expressed at highest level in liver with lesser amounts in testis, kidney, heart, lung and brain (PubMed:10885754). Not detected in spleen and skeletal muscle (PubMed:10885754, PubMed:11829493). Not detected in blood, heart, brain, testis, liver, lung, kidney, thymus or uterus (PubMed:11829493).|||Lysosome|||Probable protease (By similarity). In placenta, plays a role in promoting giant cell differentiation (PubMed:18776147). Also plays a role in placental spiral artery remodeling by direct degradation of smooth muscle alpha-actin (PubMed:18776147).|||Secreted http://togogenome.org/gene/10090:Eps8l1 ^@ http://purl.uniprot.org/uniprot/Q8R5F8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EPS8 family.|||Cytoplasm|||Detected in placenta, skin, mammary gland, bone marrow and stomach.|||Interacts with ABI1. Part of a complex that contains SOS1, ABI1 and EPS8L2. Associates with F-actin (By similarity).|||Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton (By similarity). http://togogenome.org/gene/10090:Acacb ^@ http://purl.uniprot.org/uniprot/E9Q4Z2 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activity is increased by oligomerization of the protein into filaments that correspond to the most active form of the carboxylase. The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-212 (PubMed:24913514). Inhibited by its own product malonyl-CoA. Activation by MID1IP1 is citrate dependent.|||Binds 2 magnesium or manganese ions per subunit.|||Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain (By similarity). The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA (By similarity).|||Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism (By similarity). Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (By similarity). Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (PubMed:24913514). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (PubMed:24913514).|||Mitochondrion|||Monomer, homodimer, and homotetramer. Forms filamentous polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity in a citrate-dependent manner.|||Normal morphology, fertility, growth rate and lifespan but higher than normal food consumption and fatty acid oxidation rate and decreased fat content in adipose tissue and liver (PubMed:11283375). A high-fat/high-carbohydrate diet results in maintenance of normal insulin and glucose levels with less weight gain and less fat accumulation than wild-type mice (PubMed:12920182). Elevated levels of Ucp2 in adipose tissue and heart but not in skeletal muscle or liver, and elevated levels of Ucp3 in skeletal muscle but not in heart or brown adipose tissue (PubMed:12920182). Significant decrease in body weight, weight of epidydimal fat pads and levels of hepatic triglycerides under a range of dietary conditions including normal chow diet, fasting and refeeding a fat-free high-carbohydrate diet, and a high-fat/high-carbohydrate diet (PubMed:22362781). Up-regulation of lipogenic enzymes under de novo lipogenic conditions but reduced fat accumulation in liver (PubMed:22362781). Primary cultured adipocytes show increased fatty acid and glucose oxidation rates and increased lipolysis (PubMed:15677334). Reduced heart size, reduced Mlycd and malonyl-CoA levels in mutant hearts, reduced myocardial triglyceride levels, higher myocardial oleate and glucose oxidation rates, reduced levels of Ppara and reduced activation of Mtor (PubMed:18487439, PubMed:22730442). However, it has also been reported that mutants show no differences in body weight, food intake, body composition or glucose homeostasis as compared with controls fed on chow or a high-fat diet (PubMed:20368432).|||Phosphorylated by AMPK at Ser-212 inactivates the enzyme (PubMed:24913514). Required for the maintenance of skeletal muscle lipid and glucose homeostasis (PubMed:24913514).|||The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.|||Up-regulated by endocannabinoid anandamide/AEA. http://togogenome.org/gene/10090:Il13 ^@ http://purl.uniprot.org/uniprot/P20109 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-4/IL-13 family.|||Cytokine that plays important roles in allergic inflammation and immune response to parasite infection (PubMed:15361238). Synergizes with IL2 in regulating interferon-gamma synthesis. Stimulates B-cell proliferation, and activation of eosinophils, basophils, and mast cells (By similarity). Plays an important role in controlling IL33 activity by modulating the production of transmembrane and soluble forms of interleukin-1 receptor-like 1/IL1RL1 (PubMed:34789557). Displays the capacity to antagonize Th1-driven proinflammatory immune response and downregulates synthesis of many proinflammatory cytokines including IL1, IL6, IL10, IL12 and TNF-alpha through a mechanism that partially involves suppression of NF-kappa-B (By similarity). Functions also on nonhematopoietic cells, including endothelial cells where it induces vascular cell adhesion protein 1/VCAM1, which is important in the recruitment of eosinophils. Exerts its biological effects through its receptors which comprises the IL4R chain and the IL13RA1 chain, to activate JAK1 and TYK2, leading to the activation of STAT6 (PubMed:8871614, PubMed:34795444). Aside from IL13RA1, another receptor IL13RA2 acts as a high affinity decoy for IL13 and mediates internalization and depletion of extracellular IL13 (PubMed:29305434).|||Deletion mice have increased eosinophilic inflammation and splenomegaly (PubMed:29305434). In addition, mice show exacerbated effects of IL33 administration, including increased immune cell infiltration in the peritoneum with expanded eosinophil and ILC2 populations, and reduced circulating and peritoneal sST2 (PubMed:34789557).|||Interacts with IL13RA2.|||Secreted http://togogenome.org/gene/10090:Tomm40l ^@ http://purl.uniprot.org/uniprot/Q9CZR3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tom40 family.|||Forms part of the preprotein translocase of the outer mitochondrial membrane (TOM complex) containing TOMM22, TOMM40, TOMM40L and TOMM70. Interacts with mitochondrial targeting sequences (By similarity).|||Mitochondrion outer membrane|||Potential channel-forming protein implicated in import of protein precursors into mitochondria. http://togogenome.org/gene/10090:Tlcd5 ^@ http://purl.uniprot.org/uniprot/Q3TYE7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TLCD5 family.|||Membrane http://togogenome.org/gene/10090:Mb21d2 ^@ http://purl.uniprot.org/uniprot/D3Z742 ^@ Similarity ^@ Belongs to the mab-21 family. http://togogenome.org/gene/10090:Adam24 ^@ http://purl.uniprot.org/uniprot/Q8CDV3|||http://purl.uniprot.org/uniprot/Q9R160 ^@ Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adult expression levels are reached by day 20 after birth.|||Binds 1 zinc ion per subunit.|||Expressed exclusively in testis and more specifically on the surface of mature sperm (at protein level).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Monomer.|||Plasma membrane protease present on mature sperm that may be involved in sperm function during epididymal maturation and/or fertilization.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The prodomain is removed during sperm passage through the caput epididymis after the protein has reached the cell surface. Not processed in the secretory pathway. http://togogenome.org/gene/10090:Nmi ^@ http://purl.uniprot.org/uniprot/O35309|||http://purl.uniprot.org/uniprot/Q3UJ82 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a signaling pathway regulator involved in innate immune system response (PubMed:23956435). In response to interleukin 2/IL2 and interferon IFN-gamma/IFNG, interacts with signal transducer and activator of transcription/STAT which activate the transcription of downstream genes involved in a multitude of signals for development and homeostasis (By similarity). Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5, resulting in increased STAT1- and STAT5-dependent transcription (By similarity). In response to interferon IFN-alpha, associates in a complex with transcriptional regulator IFI35 to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 (By similarity). In complex with IFI35, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries (By similarity). Negatively regulates virus-triggered type I interferon/IFN production by inducing proteosome-dependent degradation of IRF7, a transcriptional regulator of type I IFN, thereby interfering with cellular antiviral responses (PubMed:23956435). Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation, when actively released by macrophage to the extracellular space during cell injury or pathogen invasion (By similarity). Macrophage-secreted NMI activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 binding and activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines (By similarity).|||Belongs to the NMI family.|||Cytoplasm|||Expressed in macrophages.|||Induced by Sendai virus.|||Interacts with MYCN and MYC, as well as with other transcription factors with a Zip, HLH or a HLH-Zip motif. Interacts with all STAT proteins except STAT2 (By similarity). Interacts with IRF7, the interaction is direct and leads to the inhibition of IRF7-mediated type I IFN production (PubMed:23956435). Interacts (via coiled-coil domain) with TRIM21 (via the SPRY domain); the interaction leads to 'Lys-63'-linked ubiquitination of NMI. Interacts with IFI35; the interaction is direct and is facilitated by TRIM21. Interacts with TLR4; the interaction is direct and leads to NF-kappa-B activation (By similarity).|||Knockout mice show decreased inflammatory response when exposed to infection of injury, which can lead to lower inflammation-induced mortality. Display normal development of the immune system.|||May be ubiquitinated.|||Nucleus|||Secreted|||The NID domains are necessary for the interaction with IFI35 (By similarity). The NID domain 1 is necessary and IRF7 (PubMed:23956435).|||The TRIM21-mediated ubiquitinated residue is not conserved in mice, therefore it remains unclear whether the physiological role of NMI ubiquitination is preserved throughout mammals.|||The coiled-coil domain may be necessary for interaction with TRIM21 and for TRIM21-mediated ubiquitination of NMI. http://togogenome.org/gene/10090:Ccl21b ^@ http://purl.uniprot.org/uniprot/P86792|||http://purl.uniprot.org/uniprot/P86793 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Binds to CCR7 and to CXCR3. Interacts with PDPN; relocalizes PDPN to the basolateral membrane.|||Expressed strongly in lung, spleen, thymus, peripheral and mesentric lymph nodes. Also expressed in the testis, kidney, liver, and heart.|||Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Potent mesangial cell chemoattractant. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs.|||Secreted|||Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c produce identical proteins while the protein produced by Ccl21a differs at only one position. Ccl21b and Ccl21c have Leu-65 (6Ckine-Leu) while Ccl21a has 'Ser-65' (6Ckine-Ser). http://togogenome.org/gene/10090:Cacng6 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQD3|||http://purl.uniprot.org/uniprot/Q14C42|||http://purl.uniprot.org/uniprot/Q8VHW3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Cell membrane|||Detected in brain and heart (at protein level).|||Interacts with CACNA1C (PubMed:21127204). Identified in a complex with the L-type calcium channel subunits CACNA1C, CACNA2D1 and either CACNB1 or CACNB2 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit. http://togogenome.org/gene/10090:Or12k5 ^@ http://purl.uniprot.org/uniprot/Q7TRY5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ifna12 ^@ http://purl.uniprot.org/uniprot/A0A7R8C3H7|||http://purl.uniprot.org/uniprot/Q80SS5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase (By similarity).|||Secreted http://togogenome.org/gene/10090:Paox ^@ http://purl.uniprot.org/uniprot/Q8C0L6 ^@ Cofactor|||Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flavin monoamine oxidase family.|||Binds 1 FAD per subunit.|||By polyamine analogs.|||Cytoplasm|||Expression increased during embryonic development: there is a gradual increase in the tissues on going from 8.5 to 19 day embryos. In the breast, expression is very low in virgin mouse and quite high in pregnant mouse, but decreases in lactating and involuting breasts.|||Flavoenzyme which catalyzes the oxidation of N(1)-acetylspermine to spermidine and is thus involved in the polyamine back-conversion (PubMed:12660232, PubMed:28029774). Can also oxidize N(1)-acetylspermidine to putrescine. Substrate specificity: N(1)-acetylspermine = N(1)-acetylspermidine > N(1),N(12)-diacylspermine >> spermine. Does not oxidize spermidine. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs (PubMed:12660232).|||Monomer.|||N-ethylated polyamines are also good substrates for this enzyme: they have been used for cancer clinical trials. They down-regulate polyamine biosynthetic enzymes, but dramatically up-regulate SSAT synthesis, which results in mammalian cells becoming apoptotic.|||Oxidizes N(1)-acetylated polyamines on the exo-side of their N(4)-amino groups. Plant PAO oxidizes spermine on the endo-side of the N(4)-nitrogen (By similarity).|||Peroxisome|||Widely expressed at different developmental stages. Expressed at high level in the liver and the stomach, expressed at lower level in heart, spleen, thymus, small intestine, muscle, pancreas, uterus, and breast and expressed at very low level in brain, kidney, lung, testis, skin, adrenal gland and prostate gland. http://togogenome.org/gene/10090:Fam3d ^@ http://purl.uniprot.org/uniprot/P97805 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM3 family.|||Secreted http://togogenome.org/gene/10090:Idh3b ^@ http://purl.uniprot.org/uniprot/Q91VA7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the isocitrate and isopropylmalate dehydrogenases family.|||Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.|||Mitochondrion http://togogenome.org/gene/10090:Ano9 ^@ http://purl.uniprot.org/uniprot/P86044 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (PubMed:23532839). Does not exhibit calcium-activated chloride channel (CaCC) activity (By similarity). Can inhibit the activity of ANO1 (By similarity).|||In the developing respiratory system, expression is restricted to the lung epithelium at 14.5 dpc. At 14.5 dpc and 16.5 dpc, expressed in the epithelium of the esophagus, small intestine, stomach and pancreas. At 16.5 dpc, detected in bronchial epithelium. In the developing skeleton, expressed in the perichondria of developing ribs at 14.5 dpc. In developing skin, expression is detected in the most suprabasal layers at 16.5 dpc.|||Predominant expression seen in epithelial tissues.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Fau ^@ http://purl.uniprot.org/uniprot/P62862 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Component of the 40S subunit of the ribosome (PubMed:36517592). Contributes to the assembly and function of 40S ribosomal subunits (By similarity).|||Component of the 40S subunit of the ribosome.|||Cytoplasm|||FAU encodes a fusion protein consisting of the ubiquitin-like protein FUBI at the N terminus and ribosomal protein S30 at the C terminus.|||FUBI is cleaved from ribosomal protein S30 by the deubiquitinase USP36 before the assembly of ribosomal protein S30 into pre-40S ribosomal particles. FUBI removal from ribosomal protein S30 is a crucial event for the final maturation of pre-40S particles.|||In the C-terminal section; belongs to the eukaryotic ribosomal protein eS30 family.|||In the N-terminal section; belongs to the ubiquitin family.|||Lacks the typical lysine residues that participate in Ub's polyubiquitination. However contains a C-terminal di-glycine signature after its proteolytic separation from ribosomal protein S30 and could theoretically be conjugated onto target proteins.|||May have pro-apoptotic activity.|||Nucleus http://togogenome.org/gene/10090:Ptprg ^@ http://purl.uniprot.org/uniprot/A0A991ELE1|||http://purl.uniprot.org/uniprot/Q05909 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 5 subfamily.|||Detected in brain, lung, kidney, heart, liver, skeletal muscle, spleen and testes. It is developmentally regulated in the brain.|||Membrane|||Monomer; active form. Homodimer; inactive form (By similarity). Interacts with CNTN3, CNTN4, CNTN5 and CNTN6.|||Possesses tyrosine phosphatase activity. http://togogenome.org/gene/10090:Lrrn4cl ^@ http://purl.uniprot.org/uniprot/Q3TYX2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cct8l1 ^@ http://purl.uniprot.org/uniprot/Q80YT3 ^@ Similarity ^@ Belongs to the TCP-1 chaperonin family. http://togogenome.org/gene/10090:Kdm1b ^@ http://purl.uniprot.org/uniprot/Q8CIG3 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flavin monoamine oxidase family.|||Binds 3 Zn(2+) ions per subunit.|||Chromosome|||Expressed in growing oocytes and in intestinal gland.|||Histone H3 acetylation of 'Lys-9' decreases the binding of the substrate, while hyperacetylation of 'Lys-9', 'Lys-14' and 'Lys-18', phosphorylation of 'Thr3' or 'Ser-10', and methylation of 'Arg-2' or 'Arg-8' abolishes its binding. Methylation of 'Lys-9' and 'Arg-17' are the only two epigenetic modifications that have no significant effect on catalysis.|||Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4 (PubMed:19407342, PubMed:19727073). Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of GLYR1 to achieve such activity, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes (By similarity).|||Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4.|||Inhibited by tranylcypromine, but not by pargyline, deprenyl or rasagiline (PubMed:19407342). Histone H3K4me1 and H3K4me2 demethylase activity is inhibited by DNA, this inhibition is released in complex with GLYR1 (By similarity).|||Interacts with its cofactor GLYR1 at nucleosomes; this interaction stimulates H3K4me1 and H3K4me2 demethylation. In contrast to KDM1A, does not form a complex with RCOR1/CoREST.|||No effect on mouse development and oogenesis, but embryos derived from oocytes from Kdm1b-deficient females die before mid-gestation.|||Nucleus http://togogenome.org/gene/10090:Vps54 ^@ http://purl.uniprot.org/uniprot/Q5SPW0|||http://purl.uniprot.org/uniprot/Q91ZJ4 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD. Within the GARP complex, required to tether the complex to the TGN. Not involved in endocytic recycling.|||Belongs to the VPS54 family.|||Component of the Golgi-associated retrograde protein (GARP) complex, also called VFT (VPS fifty-three) complex, composed of VPS51, VPS52, VPS53 and VPS54 (By similarity). EIPR1 interacts with GARP complex and mediates its recruitment to the trans-Golgi network (By similarity). Interacts with VPS51 in an EIPR1-independent manner (By similarity).|||Defects in Vps54 are the cause of wobbler phenotype (wr). Wr is autosomal recessive and is a spontaneous mutation discovered almost 50 years ago. It causes spinal muscular atrophy and defective spermiogenesis.|||Membrane|||trans-Golgi network http://togogenome.org/gene/10090:Pglyrp3 ^@ http://purl.uniprot.org/uniprot/A1A547 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.|||Detected in lung, spleen and stomach, and at low levels in eye, heart, thymus and testis.|||Monomer. Homodimer; disulfide-linked. Heterodimer with PGLYRP4; disulfide-linked (By similarity).|||Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Binds also to Gram-negative bacteria, and has bacteriostatic activity towards Gram-negative bacteria. Plays a role in innate immunity (By similarity).|||Secreted http://togogenome.org/gene/10090:Ptpmt1 ^@ http://purl.uniprot.org/uniprot/Q66GT5 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Interacts with STYXL1; the interaction inhibits PTPMT1 catalytic activity.|||Lipid phosphatase which dephosphorylates phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG) (PubMed:21641550, PubMed:21730175). PGP is an essential intermediate in the biosynthetic pathway of cardiolipin, a mitochondrial-specific phospholipid regulating the membrane integrity and activities of the organelle (PubMed:21641550). Has also been shown to display phosphatase activity toward phosphoprotein substrates, specifically mediates dephosphorylation of mitochondrial proteins, thereby playing an essential role in ATP production (By similarity). Has probably a preference for proteins phosphorylated on Ser and/or Thr residues compared to proteins phosphorylated on Tyr residues (By similarity). Probably involved in regulation of insulin secretion in pancreatic beta cells (By similarity). May prevent intrinsic apoptosis, probably by regulating mitochondrial membrane integrity (By similarity).|||Mice die prior to E8.5.|||Mitochondrion inner membrane|||Predominantly expressed in testis. Expressed at lower level in heart, brain, spleen, lung, liver, skeletal muscle, kidney, bone marrow, eye, lymph node, smooth muscle, prostate, thymus, stomach and uterus.|||Was originally (PubMed:15247229) thought to have phosphatidylinositol 5-phosphatase activity, however, it was later shown (PubMed:16039589) that it is probably not the case in vivo. http://togogenome.org/gene/10090:Or10h28 ^@ http://purl.uniprot.org/uniprot/A0PK62|||http://purl.uniprot.org/uniprot/Q8VBW9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Opn5 ^@ http://purl.uniprot.org/uniprot/Q6VZZ7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Cell membrane|||Expressed in the brain (at protein level) (PubMed:14623103, PubMed:22043319). Weakly expressed in the skin and liver (at protein level) (PubMed:22043319). Abundantly expressed in striated muscle cells (PubMed:22043319). Expressed in Math7/Atok7-dependent retinal ganglion cells in the ganglion cell layer (at protein level) (PubMed:14623103, PubMed:22043319, PubMed:26392540, PubMed:30240620, PubMed:31607531). Additionally expressed in horizontal and amacrine cells in the inner nuclear layer of the retina (at protein level) (PubMed:22043319). Expressed around the base of hair follicles and in epidermal and sebaceous gland cells of the outer ear (at protein level) (PubMed:22043319, PubMed:31607531). Abundantly expressed in vibrissae hair follicles and weakly expressed in the vibrissae skin pad, dorsal back skin, and tail (PubMed:31607531).|||Expressed weakly in the inner retina at postnatal day 5 (P5), with expression becoming abundant in retinal ganglion cells at P8 (PubMed:30936473). Expressed throughout the retinal sublaminae layers, with abundant expression in the ganglion cell layer and nerve fiber layer at P12 (PubMed:30936473). Expressed in ganglion cells in the optic tracts, superior colliculus and lateral geniculate nucleus of the brain at P28 (PubMed:30936473). Expressed around the base of hair follicles in the dorsal ear skin, in the vibrissal nose pad, and weakly expressed below the epidermis in the vibrissal nose pad at P8 (PubMed:31607531).|||G-protein coupled receptor which selectively activates G(i) type G proteins via ultraviolet A (UVA) light-mediated activation in the retina (PubMed:22043319). Preferentially binds the chromophore 11-cis retinal and is a bistable protein that displays emission peaks at 380 nm (UVA light) and 470 nm (blue light) (PubMed:22043319, PubMed:31607531). Required for the light-response in the inner plexiform layer, and contributes to the regulation of the light-response in the nerve fiber layer, via phosphorylated DAT/SLC6A3 dopamine uptake (PubMed:30936473). Involved in local corneal and retinal circadian rhythm photoentrainment via modulation of the UVA light-induced phase-shift of the retina clock (PubMed:26392540, PubMed:30240620). Acts as a circadian photoreceptor in the outer ear and vibrissal pads, via modulation of circadian clock-gene expression in response to violet light during the light-to-dark transition phase and night phase of the circadian cycle (PubMed:31607531). Required in the retina to negatively regulate hyaloid vessel regression during postnatal development via light-dependent OPN5-SLC32A1-DRD2-VEGFR2 signaling (PubMed:30936473). Involved in the light-dependent regulation of retina and vitreous compartment dopamine levels (PubMed:30936473).|||It is uncertain whether Cys-315 or Cys-316 is palmitoylated.|||Ultrastructure of the retina is normal (PubMed:30936473, PubMed:30240620, PubMed:26392540). Newborn mice show normal hyaloid vessel numbers and normal vessel cellularity (PubMed:30936473). Retinas show normal expression patterns of rod and cone opsins including Opn4 (PubMed:26392540, PubMed:30240620). Decreased activated Vegfr2 in the hyaloid vessels and increased activated Akt1 at P5 (PubMed:30936473). Reduced levels of dopamine in the retina, however increased levels in the vitreous at P6 (PubMed:30936473). Reduced number of hyaloid blood vessels due to precocious regression, however no change in abundance of Vegfa or Flt1 at P8 (PubMed:30936473). Expression of tyrosine hydroxylase Th in retinal cell processes at P8, with increased expression in developed dopaminergic amacrine cells at P15 (PubMed:30936473). Loss of retinal and corneal circadian rhythm photoentrainment (PubMed:26392540, PubMed:30240620). Reduced UVA-induced phase-shift response and Fos expression in the suprachiasmatic nuclei (SCN) in the brain (PubMed:30240620). Abolishes retinaldehyde-dependent photoentrainment in the dermal tissues of the outer ear and vibrissal pad (PubMed:31607531). Loss of phase shifting activity in response to violet light and expression of circadian clock-genes in the skin of the outer ear during light-to-dark cycle, including Per1, Per2, Cry2, Dbp and Nr1d2 (PubMed:31607531). Pde6b and Opn5 double knockout mice also show loss of retinal ultrastructures and a more severe reduction in the rate of circadian photoentrainment, light-induced phase-shift response and Fos expression in the SCN (PubMed:30240620). http://togogenome.org/gene/10090:Napa ^@ http://purl.uniprot.org/uniprot/Q9DB05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNAP family.|||Cell membrane|||Interacts with PRKCABP, and disrupts the interaction between GRIA2 and PRKCABP, leading to the internalization of GRIA2 (By similarity). Found in a complex with VAMP8 (By similarity). Component of a SNARE-like complex that contains at least ZW10, USE1L, RINT1, STX18 and NAPA/SNAP-alpha (By similarity). Interacts with VTI1A (PubMed:9705316). Interacts with STX12 (By similarity). Interacts with GNA12 (via N-terminus); the interaction promotes CDH5 localization to plasma membrane (By similarity).|||Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus. Together with GNA12 promotes CDH5 localization to plasma membrane. http://togogenome.org/gene/10090:Ipo11 ^@ http://purl.uniprot.org/uniprot/Q8K2V6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the importin beta family.|||Cytoplasm|||Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of RPL12, and of UBE2E3 (By similarity).|||Interacts with UBE2E3 and RPL12.|||Nucleus http://togogenome.org/gene/10090:Or4d1 ^@ http://purl.uniprot.org/uniprot/Q5SW48 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dpf1 ^@ http://purl.uniprot.org/uniprot/Q6GTK4|||http://purl.uniprot.org/uniprot/Q9QX66 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At embryonic stages, predominant expression in the nervous system. Expressed specifically in postmitotic neurons (at protein level).|||Belongs to the requiem/DPF family.|||Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin.|||Cytoplasm|||Low levels at embryonic day 9.5, and then sharp increase since embryonic day 12. In the developing forebrain and cerebellar primordium, strictly expressed in postmitotic neurons.|||May have an important role in developing neurons by participating in regulation of cell survival, possibly as a neurospecific transcription factor. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.|||Nucleus http://togogenome.org/gene/10090:Gdpgp1 ^@ http://purl.uniprot.org/uniprot/Q3TLS3|||http://purl.uniprot.org/uniprot/Q8C3E3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GDPGP1 family.|||Cytoplasm|||Highly expressed in the nervous and male reproductive systems compared to kidney, liver and heart.|||Specific and highly efficient GDP-D-glucose phosphorylase regulating the levels of GDP-D-glucose in cells.|||The orthologs in A.thaliana are GDP-L-galactose phosphorylases catalyzing the first reaction of the Smirnoff-Wheeler pathway, the major route to ascorbate biosynthesis in plants. http://togogenome.org/gene/10090:Cyp27a1 ^@ http://purl.uniprot.org/uniprot/Q9DBG1 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-125 and Lys-285 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the cytochrome P450 family.|||Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid. Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways. May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism (By similarity). Plays a role in cholestanol metabolism in the cerebellum (PubMed:28190002). Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation. Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (By similarity).|||Expressed in the gray and white matter of cerebellum (at protein level).|||Interacts with HSP70; this interaction is required for initial targeting to mitochondria.|||Mitochondrion inner membrane|||Mutant mice show cholestanol accumulation in the cerebellum. http://togogenome.org/gene/10090:Cenatac ^@ http://purl.uniprot.org/uniprot/Q4VA36 ^@ Function|||PTM|||Subunit ^@ Acetylated. Acetylation oscillates throughout the cell cycle, and the acetylation state at Lys-31 is regulated by the deacetylase SIRT1 and the acetyltransferase NAT10. Deacetylated CENATAC is responsible for its centrosome targeting, and acetylated CENATAC promotes SASS6 degradation by enhancing the binding affinity of SASS6 for APC/C E3 ubiquitin-protein ligase complex/FZR1.|||Component of the minor spliceosome that promotes splicing of a specific, rare minor intron subtype. Negative regulator of centrosome duplication. Constrains centriole number by modulating the degradation of the centrosome-duplication-associated protein SASS6 in an acetylation-dependent manner. SIRT1 deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly. The CENATAC acetylation level is restored in mitosis by NAT10, promoting SASS6 proteasome degradation by facilitating SASS6 binding to APC/C E3 ubiquitin-protein ligase complex/FZR1.|||Interacts with SASS6; the interaction increases with CENATAC acetylation. http://togogenome.org/gene/10090:Ascl1 ^@ http://purl.uniprot.org/uniprot/Q02067 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Between 8.5 dpc and 10.5 dpc it is found in the neuroepithelium of the midbrain and ventral forebrain, as well as in the spinal cord. Between 10.5 dpc and 12.5 dpc its expression pattern changes from a restricted to a widespread zone, it is then found at variable levels in the ventricular zone in all regions of the brain, where is expressed in a subset of p2 progenitors that can give rise to either V2a or V2b interneuron subtypes. From 12.5 dpc to postnatal stages it is also expressed in cells outside of the ventricular zone through the brain, and in addition it is also expressed during development of the olfactory epithelium and neural retina. At 12.5 dpc, it is highly expressed by differentiating enteric neurons in the mesenchyme of the stomach. At 14.5 and 16.5 dpc, it is also expressed in the epithelium of the glandular stomach (PubMed:18173746).|||Developing CNS and PNS at embryonic and postnatal stages. Expressed in the epithelium of glandular stomach (PubMed:18173746).|||Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3.|||Lethality at birth caused by severe defects in neurogenesis. While the brain and spinal cord of the mutants appear normal, their olfactory epithelium and sympathetic, parasympathetic and enteric ganglia are severely affected. In the olfactory epithelium, neuronal progenitors die at an early stage, whereas the non-neuronal supporting cells are present. In sympathetic ganglia, the development of neuronal precursors is arrested, preventing the generation of sympathetic neurons, without affecting glial precursor cells. Homozygous MASH1-null mice have smaller stomachs than the control, and neuroendocrine cells are mostly missing, while chief, parietal and pit cells are formed. However, the wall of the glandular stomach is much thicker, has a deeper fold structure, and the forestomach epithelium is villous compared to controls (PubMed:18173746).|||Nucleus|||Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways (PubMed:24243019). Directly binds the E box motif (5'-CANNTG-3') on promoters and promotes transcription of neuronal genes (PubMed:20107439, PubMed:24243019, PubMed:27281220). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (PubMed:20107439, PubMed:24243019, PubMed:27281220). Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS (PubMed:8217843). Essential for the generation of olfactory and autonomic neurons (PubMed:8221886). Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4-NOTCH signaling activation (PubMed:16020526, PubMed:17728344). Involved in the regulation of neuroendocrine cell development in the glandular stomach (PubMed:18173746). http://togogenome.org/gene/10090:Fbh1 ^@ http://purl.uniprot.org/uniprot/Q8K2I9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3'-5' DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks (By similarity). Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination (PubMed:24108124). Also promotes cell death and DNA double-strand breakage in response to replication stress: together with MUS81, promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress. Plays a major role in remodeling of stalled DNA forks by catalyzing fork regression, in which the fork reverses and the two nascent DNA strands anneal. In addition to the helicase activity, also acts as the substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex, a complex that mediates ubiquitination of RAD51, leading to regulate RAD51 subcellular location (By similarity).|||Belongs to the helicase family. UvrD subfamily.|||Chromosome|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBH1) composed of CUL1, SKP1, RBX1 and FBH1 (By similarity). Interacts with RPA2 (By similarity). Interacts with RAD51 (PubMed:24108124). Interacts (via PIP-box and RanBP2-type zinc finger) with PCNA (By similarity).|||The PIP-box mediates the interaction with PCNA.|||Ubiquitinated. Ubiquitination by the DCX(DTL) complex, also named CRL4(CDT2), leading to its degradation: ubiquitination takes place after its localization to DNA damage sites, possibly to facilitate the translesion synthesis (TLS) pathway. http://togogenome.org/gene/10090:Msmo1 ^@ http://purl.uniprot.org/uniprot/Q9CRA4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sterol desaturase family.|||Catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be subsequently metabolized to cholesterol.|||Endoplasmic reticulum membrane|||The histidine box domains may contain the active site and/or be involved in metal ion binding. http://togogenome.org/gene/10090:Tango6 ^@ http://purl.uniprot.org/uniprot/Q8C3S2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Tango6 family.|||Membrane http://togogenome.org/gene/10090:Elavl1 ^@ http://purl.uniprot.org/uniprot/P70372 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM elav family.|||Cytoplasm|||Methylated at Arg-217 by CARM1 in T-cells in response to LPS challenge.|||Monomer and homodimer (in vitro). Interacts with ANP32A (By similarity). Interacts with ZNF385A; the interaction is indirect and mRNA-dependent and may regulate p53/TP53 expression (PubMed:21402775). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with AGO1 and AGO2. Interacts with IGF2BP1. Interacts with IGF2BP2 and IGF2BP3. Interacts with HNRNPL (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner. Interacts with ILF3; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with PLEKHN1 (By similarity). Interacts with SHFL; the interaction increases in presence of RNA (By similarity). Interacts with YBX1; interaction recruits ELAVL1 on C5-methylcytosine (m5C)-containing mRNAs, thereby promoting mRNA stability (By similarity). Interacts with FXR1 (By similarity).|||Nucleus|||P-body|||Phosphorylated by MAPKAPK2. Phosphorylated by PRKCD.|||RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability. Involved in embryonic stem cell (ESC) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESC differentiation (PubMed:24394384). Has also been shown to be capable of binding to m6A-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (By similarity). Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro (By similarity). With ZNF385A, binds the 3'-UTR of p53/TP53 mRNA to control their nuclear export induced by CDKN2A. Hence, may regulate p53/TP53 expression and mediate in part the CDKN2A anti-proliferative activity. May also bind with ZNF385A the CCNB1 mRNA (PubMed:21402775). Increases the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR (PubMed:27616329).|||Stress granule|||The first RRM (RNA recognition motif) domain is essential for binding to AU-rich elements. http://togogenome.org/gene/10090:Trim44 ^@ http://purl.uniprot.org/uniprot/Q9QXA7 ^@ Developmental Stage|||Function|||Subunit|||Tissue Specificity ^@ Expressed mainly in brain with high level in cerebral hemispheres and cerebellum. Lower expression in kidney, lung and spleen. In brain is detected in the hippocampus, thalamic and pretectal nuclei, substantia nigra, the dorsal part of the medulla, the cerebellum, in the olfactory nucleus, other cortical areas apart from hippocampus and the striatum. Indeed expression is confined in neuronal somata namely in the CA3 region and dentate gyrus of the hippocampus, caudate-putamen, parabranchial nucleus, olfactory nucleus, cortex, deep cerebellar nuclei and thalamus. Also highly expressed in the spleen. thymus and testis.|||Expression was detected in brain at 14 dpc and 18 dpc. At P5 expression in cerebellum is detected in both the dividing neuroblasts and post-mitotic neurons of the external granular layer as well as in the developing granule neurons of the internal granular layer while the expression in Purkinje cells was lower. At P10 the expression in external and internal granular layers remained strong while at the same time the Purkinje cells also acquired significant level of expression.|||Interacts (via coiled coil) with TRIM17 (via coiled coil).|||May play a role in the process of differentiation and maturation of neuronal cells (By similarity). May regulate the activity of TRIM17 (By similarity). Is a negative regulator of PAX6 expression (By similarity). http://togogenome.org/gene/10090:P2ry14 ^@ http://purl.uniprot.org/uniprot/A0A0G2JEW9|||http://purl.uniprot.org/uniprot/Q544F4|||http://purl.uniprot.org/uniprot/Q9ESG6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for UDP-glucose coupled to G-proteins. http://togogenome.org/gene/10090:Tas2r125 ^@ http://purl.uniprot.org/uniprot/Q7M710 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Or5p57 ^@ http://purl.uniprot.org/uniprot/Q8VEZ0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Probable odorant receptor, which recognizes only aliphatic alcohols, suggesting that it may convey a 'woody' or 'sweet' sour. http://togogenome.org/gene/10090:Ggt7 ^@ http://purl.uniprot.org/uniprot/Q99JP7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gamma-glutamyltransferase family.|||Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.|||Heterodimer composed of the light and heavy chains. The active site is located in the light chain.|||Hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors.|||Membrane http://togogenome.org/gene/10090:H2-M2 ^@ http://purl.uniprot.org/uniprot/Q6W9L1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Mup10 ^@ http://purl.uniprot.org/uniprot/A2BIN1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Tars ^@ http://purl.uniprot.org/uniprot/Q9D0R2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage.|||Cytoplasm|||Homodimer.|||ISGylated. http://togogenome.org/gene/10090:Reep2 ^@ http://purl.uniprot.org/uniprot/C1IE02|||http://purl.uniprot.org/uniprot/Q8VCD6 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DP1 family.|||Interacts with odorant receptor proteins.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Required for endoplasmic reticulum (ER) network formation, shaping and remodeling. May enhance the cell surface expression of odorant receptors (By similarity). http://togogenome.org/gene/10090:Esrrg ^@ http://purl.uniprot.org/uniprot/P62509 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by PCAF/KAT2 (in vitro).|||Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Cardiomyocyte-specific double konckout for ESRRA and ESRRG are slower at gaining weight, smaller and shorter from 5 to 7 days of age compared to controls. They show decreased absolute weight of most internal organs except the heart. They have about 70% decreased plasma IGF1 levels but normal plasma growth hormone levels. At 14-15 days, mutants develop lethal dilated cardiomyopathy and heart failure.|||Highly expressed in the heart, brain and kidney and low expression in the liver.|||Homodimer. Interacts with NRIP1, NCOA1 and NCOR2 (By similarity). Binds TLE1, PNRC1 and PNRC2 (By similarity). Binds GRIP1.|||No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG.|||Nucleus|||Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements. Induces the expression of PERM1 in the skeletal muscle.|||Phosphorylation on Ser-45 enhances sumoylation on Lys-40 thus repressing transcriptional activity.|||Sumoylation on Lys-40 is enhanced by phosphorylation at Ser-45 and represses transcriptional activity. http://togogenome.org/gene/10090:D130043K22Rik ^@ http://purl.uniprot.org/uniprot/Q5SZV5 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Early endosome membrane|||Expressed in the frontal neocortex, glanglionic eminence, mesencephalon and cerebellum at 13.5 dpc. More prominently expressed in the developing cerebral neocortex and mesencephalon at 15.5 dpc and in the cortical plate and in the remnant of the ventricular zone at 18.5 dpc.|||Homodimer. Interacts with AP2M1; required for clathrin-mediated endocytosis (By similarity).|||Involved in neuronal migration during development of the cerebral neocortex. May function in a cell autonomous and a non-cell autonomous manner and play a role in appropriate adhesion between migrating neurons and radial glial fibers. May also regulate growth and differentiation of dendrites (By similarity).|||N-glycosylated.|||O-glycosylated.|||Shedding of the extracellular domain and intramembrane cleavage produce several proteolytic products. The intramembrane cleavage releases a soluble cytoplasmic polypeptide that translocates to the nucleolus (By similarity). http://togogenome.org/gene/10090:Gprc5a ^@ http://purl.uniprot.org/uniprot/G5E8C3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5d47 ^@ http://purl.uniprot.org/uniprot/A2BHP6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Man1a2 ^@ http://purl.uniprot.org/uniprot/P39098 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 47 family.|||Golgi apparatus membrane|||Inhibited by both 1-deoxymannojirimycin and kifunensine.|||Involved in the maturation of Asn-linked oligosaccharides. Progressively trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2). http://togogenome.org/gene/10090:Krt26 ^@ http://purl.uniprot.org/uniprot/Q3TRJ4 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Nek2 ^@ http://purl.uniprot.org/uniprot/O35942 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autophosphorylation. Protein phosphatase 1 represses autophosphorylation and activation of isoform 1 by dephosphorylation. Phosphorylation by STK3/MST2 is necessary for its localization to the centrosome.|||Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Cytoplasm|||Forms homodimers and heterodimers. Interacts with CDC20, CTNB1, MAD1L1, MAD2L1, MAPK, NEK11, NPM1, NDC80, PCNT, PPP1CA, PPP1CC and SGO1. Interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain) (By similarity). Interacts with NECAB3 and HMGA2 (PubMed:14697346, PubMed:14668482). Interacts with CEP68; the interaction leads to phosphorylation of CEP68. Interacts with CNTLN; the interaction leads to phosphorylation of CNTLN. Interacts with CEP85 (By similarity).|||Its catalytic activity is inhibited by the inhibitor CCT241950. In the presence of this inhibitor, displays an autoinhibited conformation: Tyr-70 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix.|||Most abundantly expressed in testis. Low levels found in mid-gestation embryo, ovary, placenta, intestine, thymus and skin. Within the testis, expression restricted to germ cells with highest levels detected in spermatocytes at pachytene and diplotene stages. Also expressed in meiotic pachytene oocytes.|||Nucleus|||Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (By similarity). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (By similarity). Phosphorylates and activates NEK11 in G1/S-arrested cells. Involved in the regulation of centrosome disjunction (By similarity).|||The leucine-zipper domain is required for its dimerization and activation.|||centromere|||centrosome|||kinetochore|||nucleolus|||spindle pole http://togogenome.org/gene/10090:Traf1 ^@ http://purl.uniprot.org/uniprot/P39428 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter molecule that regulates the activation of NF-kappa-B and JNK. Plays a role in the regulation of cell survival and apoptosis. The heterotrimer formed by TRAF1 and TRAF2 is part of a E3 ubiquitin-protein ligase complex that promotes ubiquitination of target proteins, such as MAP3K14. The TRAF1/TRAF2 complex recruits the antiapoptotic E3 protein-ubiquitin ligases BIRC2 and BIRC3 to TNFRSF1B/TNFR2 (By similarity).|||Cleavage by CASP8 liberates a C-terminal fragment that promotes apoptosis and inhibits the activation of NF-kappa-B in response to TNF signaling.|||Cytoplasm|||Homotrimer (By similarity). Heterotrimer with TRAF2 (PubMed:8069916). Interacts with TNFRSF1A/TNFR1, TNFRSF1B/TNFR2, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13C, TNFRSF18/AITR, TNFRSF17/BCMA, TNFRSF19/TROY, TNFRSF19L/RELT, XEDAR, EDAR, Epstein-Barr virus BNFL1/LMP-1, TANK/ITRAF, TRAIP and RIPK2 (PubMed:8069916, PubMed:9104814, PubMed:18429822). Interacts with BIRC2 and BIRC3 N-terminus; a single BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 and TRAF2. Interacts with MAP3K14 (By similarity). Interacts with NFATC2IP, TRAFD1 and with HIVEP3 (PubMed:11804591, PubMed:16352630, PubMed:18849341). Interacts with GPS2 (PubMed:22424771).|||Lacks a RING domain and has therefore no E3 ubiquitin-protein ligase activity by itself.|||No visible phenotype. Mice have normal B-cell proliferation and antibody response, but increased T-cell proliferation in response to CD3 signaling. Their T-cells show enhanced activation of JNK and NF-kappa-B. Mice are highly susceptible to TNF-induced skin necrosis.|||Polyubiquitinated by BIRC2 and/or BIRC3, leading to its subsequent proteasomal degradation (By similarity). Ubiquitinated by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:23542741).|||The MATH/TRAF domain binds to receptor cytoplasmic domains.|||The coiled coil domain mediates homo- and hetero-oligomerization. http://togogenome.org/gene/10090:Pmaip1 ^@ http://purl.uniprot.org/uniprot/Q9JM54 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMAIP1 family.|||Detected in thymocytes after irradiation with X-rays. Not detectable in untreated thymocytes (at protein level). Detected in embryonic neural precursor cells of the telencephalon Constitutively expressed at low levels in adult brain, testis, thymus, spleen, lung and kidney.|||Interacts with MCL1 (PubMed:10807576, PubMed:15901672, PubMed:15694340, PubMed:17389404). Interacts with BCL2A1 (By similarity). Interacts with BAX (By similarity). Interacts with BCL2L10 (By similarity).|||Mitochondrion|||Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1 (By similarity). Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1.|||The BH3 motif is essential for pro-apoptotic activity.|||Up-regulated after exposure to ionizing radiation and other genotoxic agents. Up-regulation is mediated by p53. http://togogenome.org/gene/10090:Or14c40 ^@ http://purl.uniprot.org/uniprot/Q7TS10 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or3a4 ^@ http://purl.uniprot.org/uniprot/Q7TRX3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arap3 ^@ http://purl.uniprot.org/uniprot/Q8R5G7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts (via SAM domain) with INPPL1/SHIP2.|||Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts preferentially on ARF5 and on RHOA.|||Tyrosine phosphorylated at a low basal level. PDGF treatment stimulates phosphorylation. Tyrosine phosphorylation is increased in cells that are in the process of becoming attached to a substrate and that start spreading and flattening.|||cytoskeleton|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Pax5 ^@ http://purl.uniprot.org/uniprot/Q02650 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in all B-lymphoid organs, in the embryonic midbrain and in adult testis.|||Interacts with ETS1; this interaction alters PAX5 DNA-binding properties. Binds DNA as a monomer. Interacts with TBP; this interaction allows PAX5 to interact with the basal transcription machinery. Interacts with RB1. Interacts with TLE4 (By similarity). Interacts with DAXX (PubMed:11799127).|||Mutant mice fail to produce small pre-B, B, and plasma cells and therefore lack any immunoglobulin in their serum owing to a complete arrest of B-cell development at an early stage.|||Nucleus|||O-glycosylated.|||Phosphorylated by SYK. This phosphorylation plays an important role in the abolition of BLIMP1 repression by PAX5 in order to trigger plasma cell differentiation.|||Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage (PubMed:9042861). Fulfills a dual role by repressing B-lineage inappropriate genes and simultaneously activating B-lineage-specific genes (PubMed:16546096). In turn, regulates cell adhesion and migration, induces V(H)-to-D(H)J(H) recombination, facilitates pre-B-cell receptor signaling and promotes development to the mature B-cell stage (PubMed:9042861, PubMed:16546096). Repression of the cohesin-release factor WAPL causes global changes of the chromosomal architecture in pro-B cells to facilitate the generation of a diverse antibody repertoire (By similarity). http://togogenome.org/gene/10090:Tent4b ^@ http://purl.uniprot.org/uniprot/Q68ED3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-B-like family.|||Component of a nucleolar TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes.|||Cytoplasm|||Nucleus|||Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3' poly(A) tail creating a heterogeneous 3' poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation (By similarity). Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Doesn't need a cofactor for polyadenylation activity (in vitro). Plays a role in replication-dependent histone mRNA degradation, probably through terminal uridylation of mature histone mRNAs. May play a role in sister chromatid cohesion (By similarity).|||Was originally thought to have DNA polymerase activity.|||nucleolus http://togogenome.org/gene/10090:Oip5 ^@ http://purl.uniprot.org/uniprot/A2AQ14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mis18 family.|||Chromosome|||Homodimer, and heterodimer with MIS18A. Identified in a complex containing MIS18A, OIP5/MIS18B, MIS18BP1, RBBP7 and RBBP4.|||Nucleus|||Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.|||centromere http://togogenome.org/gene/10090:Olfml1 ^@ http://purl.uniprot.org/uniprot/Q8BSH2 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Sptbn1 ^@ http://purl.uniprot.org/uniprot/Q62261 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the spectrin family.|||Cell membrane|||Cytoplasm|||Endomembrane system|||Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function.|||Interacts with ANK2 (PubMed:15262991). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Like erythrocyte spectrin, the spectrin-like proteins are capable to form dimers which can further associate to tetramers (By similarity). Interacts with CAMSAP1 (By similarity). Can form heterodimers with SPTAN1.|||Isoform 2 is expressed in brain, heart and liver throughout embryonic development. Isoform 1 is mainly expressed in neonatal developing ventricular cardiomyocytes.|||Isoform 2 is present in brain, heart, kidney and liver (at protein level).|||M line|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Tyrp1 ^@ http://purl.uniprot.org/uniprot/P07147|||http://purl.uniprot.org/uniprot/Q3UFS3 ^@ Caution|||Cofactor|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tyrosinase family.|||Contains bound zinc ions after heterologous expression in insect cells.|||Defects in Tyrp1 are the cause of the brown (b) phenotype. Brown mice have a brown or hypopigmented coat.|||Glycosylated.|||Melanosome membrane|||Monomer (By similarity). Interacts with ATP7A (PubMed:18650808). Interacts with SLC45A2 (PubMed:35469906).|||Pigment cells.|||Plays a role in melanin biosynthesis (PubMed:2245916). Catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into indole-5,6-quinone-2-carboxylic acid (PubMed:7813420). May regulate or influence the type of melanin synthesized (PubMed:7813420, PubMed:2245916). Also to a lower extent, capable of hydroxylating tyrosine and producing melanin (PubMed:1537333).|||The precise function of this protein in melanin biosynthesis is still under debate. DHICA oxidase activity is controversial. The mouse protein has been shown to have DHICA oxidase activity (PubMed:7813420). In contrast, the human protein was shown lack DHICA oxidase activity, or to have DHICA oxidase activity only in the presence of Cu(2+), but not with Zn(2+) (By similarity). http://togogenome.org/gene/10090:Mpig6b ^@ http://purl.uniprot.org/uniprot/D7PDD4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contains both a transmembrane region and 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. The 2 ITIM motifs of isoform B are required for the inhibition of CLEC1B and GP6:FCER1G signaling and platelet activation.|||Expressed in mature megakaryocytes and platelets. Not expressed by immature megakaryocytes.|||Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (PubMed:23112346). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide (By similarity). This regulation of megakaryocate function as well as platelet production ann activation is done through the inhibition (via the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling (PubMed:23112346). Appears to operate in a calcium-independent manner (By similarity).|||Interacts (via ITIM motif) with PTPN6 and PTPN11 (PubMed:23112346). Binds to heparin (By similarity).|||May be O-glycosylated.|||Mutant mice exhibit macrothrombocytopenia (reduced platelet numbers and the presence of enlarged platelets) and a susceptibility to bleeding because of defective platelet production and function. They show an increased platelet turnover leading to reduced platelet numbers. Their megakaryocytes exhibit reduced integrin-mediated functions, defective formation of proplatelets as well as an increased metalloproteinase production.|||N-glycosylated.|||Phosphorylated. http://togogenome.org/gene/10090:Polk ^@ http://purl.uniprot.org/uniprot/Q9QUG2 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-Y family.|||DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls (PubMed:12432099). Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity (By similarity).|||Detected at low levels in heart, brain, lung, liver, kidney and testis.|||Divalent metal cations. Prefers Mg(2+), but can also use Mn(2+).|||Interacts with PCNA (By similarity). Interacts with REV1 (PubMed:14657033).|||Nucleus|||The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity. http://togogenome.org/gene/10090:Dntt ^@ http://purl.uniprot.org/uniprot/P09838|||http://purl.uniprot.org/uniprot/Q3UZ80 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3'-to-5' DNA exonuclease. Involved in the generation of diversity in the antigen-binding region of immunoglobulin heavy and light chains and T-cell receptors during B- and T-cell development. Acts on single-stranded and double-stranded DNA with 3' or 5' extensions, but not on double-stranded DNA with blunt ends. Attenuates not only isoform TDT-S-catalyzed N addition, but also P (palindromic) addition in coding joins (PubMed:11938351). Lacks terminal transferase activity (PubMed:11136823, PubMed:7556063).|||Belongs to the DNA polymerase type-X family.|||Can also utilize other divalent cations, such as Mn(2+) and Co(2+) (in vitro).|||Cytoplasm|||Exhibits 3'-to-5' DNA exonuclease activity (EC=3.1.11.-) (PubMed:23856622). May have a shorter half-life than isoform TDT-S (PubMed:7556063, PubMed:10878023).|||Interacts with PRP19 and DNTTIP1. Forms a ternary complex with DNTTIP2 and core histone. Released from this complex by PCNA. Interacts with TRERF1.|||Isoform TDT-L: Expressed in the thymus, and, at lower levels, in the bone marrow (PubMed:8464703, PubMed:11136823, PubMed:7556063). Detected in both cycling and noncycling pro-B and pre-B cells (at protein level) (PubMed:11938351). Isoform TDT-S: Expressed in both cycling and noncycling pro-B, but not pre-B, cells (at protein level) (PubMed:11938351). Not detected in mature peripheral or germinal center B cells (PubMed:11938351).|||Major form in the thymus and the bone marrow (PubMed:8464703, PubMed:11136823). Catalyzes the nontemplated addition of nucleoside triphosphate to coding ends during V(D)J recombination (PubMed:23856622). May have a longer half-life than isoform TDT-L (PubMed:7556063).|||Nucleus|||Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator.|||Transferase that catalyzes the nontemplated addition of nucleoside triphosphate to coding ends during V(D)J recombination (N addition). Involved in the generation of diversity in the antigen-binding region of immunoglobulin heavy and light chains and T-cell receptors during B- and T-cell development. Does not act on double-stranded DNA with blunt ends. http://togogenome.org/gene/10090:Vmn2r50 ^@ http://purl.uniprot.org/uniprot/E9PW61 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam168a ^@ http://purl.uniprot.org/uniprot/Q68FE1|||http://purl.uniprot.org/uniprot/Q8BGZ2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the FAM168 family.|||In cancer context, protects cells from induced-DNA damage and apoptosis. Acts, at least in part, through PI3K/AKT/NFKB signaling pathway and by preventing POLB degradation. Decreases POLB ubiquitation and stabilizes its protein levels.|||Interacts with POLB. Interacts with AKT1 and MT1X. May interact with FAM168B. http://togogenome.org/gene/10090:Vmn1r17 ^@ http://purl.uniprot.org/uniprot/Q8R2D8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il12a ^@ http://purl.uniprot.org/uniprot/F8WI71|||http://purl.uniprot.org/uniprot/P43431|||http://purl.uniprot.org/uniprot/Q549G3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-6 superfamily.|||Deletion mutant mice display normal development (PubMed:8766560). However, they are unable to restrict the progression of Leishmania major infection with strong parasite load in lymphoid tissues observed (PubMed:8766560). In addition, regulatory T-cells are functionally defective and mice are unable to control colitis (resembling inflammatory bowel disease, IBD)(PubMed:18033300).|||Heterodimer with IL12B; disulfide-linked (PubMed:1350290). This heterodimer is known as interleukin IL-12 (PubMed:1350290). Heterodimer with EBI3/IL27B; not disulfide-linked (By similarity). This heterodimer is known as interleukin IL-35 (By similarity). Interacts with NBR1; this interaction promotes IL-12 secretion (PubMed:34374750).|||Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12.|||Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine. IL-12 is primarily produced by professional antigen-presenting cells (APCs) such as B-cells and dendritic cells (DCs) as well as macrophages and granulocytes and regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma), favors the differentiation of T-helper 1 (Th1) cells and is an important link between innate resistance and adaptive immunity (PubMed:8766560). Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits. Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2. In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes (By similarity). As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and functions also as an immune-suppressive cytokine (PubMed:18033300, PubMed:30197594). Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers. Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites (By similarity).|||Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine. IL-12 is primarily produced by professional antigen-presenting cells (APCs) such as B-cells and dendritic cells (DCs) as well as macrophages and granulocytes and regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma), favors the differentiation of T-helper 1 (Th1) cells and is an important link between innate resistance and adaptive immunity. Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits. Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2. In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes. As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and functions also as an immune-suppressive cytokine. Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers. Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites.|||Secreted http://togogenome.org/gene/10090:Lhx8 ^@ http://purl.uniprot.org/uniprot/O35652 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Limited spatially to the medical ganglionic eminence and the mesenchyme surrounding the oral cavity and temporally from middle embryonic to early postnatal development.|||Nucleus|||Transcription factor involved in differentiation of certain neurons and mesenchymal cells. http://togogenome.org/gene/10090:Jagn1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SV89|||http://purl.uniprot.org/uniprot/Q5XKN4 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the jagunal family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum transmembrane protein involved in vesicle-mediated transport, which is required for neutrophil function. Required for vesicle-mediated transport; it is however unclear whether it is involved in early secretory pathway or intracellular protein transport. Acts as a regulator of neutrophil function, probably via its role in vesicle-mediated transport: required for defense against fungal pathogens and for granulocyte colony-stimulating factor (GM-CSF) signaling pathway; possibly by regulating glycosylation and/or targeting of proteins contributing to the viability and migration of neutrophils.|||Experiments in human confirm the importance of JAGN1 in neutrophil function with some differences. Defects in JAGN1 cause neutropenia in human, while it is not the case in mice lacking Jagn1. Mutant mice show defects in neutrophil migration and increased susceptibility to fungal infections due to defective killing capacity of neutrophil granulocytes.|||Interacts with COPA, COPB2 and COPG2.|||Lethality around embryonic day 8.5. Mice carrying a hematopoietic lineage-specific deletion of Jagn1 show defects in neutrophil-dependent immune response to the fungal pathogen Candida albicans. Neutrophils display defects in the glycosylation of proteins involved in cell adhesion and cytotoxicity as well as impaired migration in response to Candida albicans infection and impaired formation of cytotoxic granules.|||Membrane http://togogenome.org/gene/10090:Vmn2r103 ^@ http://purl.uniprot.org/uniprot/E9PWW0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp280b ^@ http://purl.uniprot.org/uniprot/Q505F4 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Or2b7 ^@ http://purl.uniprot.org/uniprot/Q7TQU0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grin2d ^@ http://purl.uniprot.org/uniprot/Q03391 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2D/GRIN2D subfamily.|||Cell membrane|||Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:1385220). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).|||Detected in neonate brain synaptosomes (at protein level).|||Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1385220). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Interacts with PDZ domains of PATJ and DLG4 (By similarity).|||Mice are born at the expected Mendelian rate, are viable and fertile. Their brains appear grossly normal. Mutant mice show reduced spontaneous locomotion activity, but have no visible impairment of motor skills. They have normal exploratory behavior, but their behavior in a new situation suggests increased novelty preference.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Prm3 ^@ http://purl.uniprot.org/uniprot/Q62100 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protamine P3 family.|||Chromosome|||Nucleus|||Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.|||Testis. http://togogenome.org/gene/10090:Sox13 ^@ http://purl.uniprot.org/uniprot/Q04891 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in beta-cells in pancreatic islets of Langerhans (at protein level) (PubMed:10871192). Expressed in a subset of invariant natural killer (iNK) T-cells (at protein level) (PubMed:30413363). Expressed in oligodendroglial cells in the spinal cord (at protein level) (PubMed:26525805). In the hematopoietic system, expressed in gamma-delta T-cell lineage, specifically in immature Vgamma2-positive gamma-delta thymocytes, with expression decreasing upon maturation (PubMed:17218525, PubMed:23562159, PubMed:30413363). Expressed in DN1d cells, a subset of DN1 (TCR, CD4 and CD8 negative, also known as TN1) thymocyte progenitors, and in DN2 (also known as TN2) thymocyte progenitors (PubMed:17218525, PubMed:30413363). Expressed in the ovary and kidney (PubMed:9524265). Expressed in the peripheral lymphoid organs (PubMed:17218525).|||Expressed in the visceral mesoderm of the yolk sac from 9.5 dpc to 15.5 dpc (at protein level) (PubMed:16835393, PubMed:30413363). Expressed in the sclerotome of developing somites and the derivative vertebrae and ribs between 9.5 dpc and 12.5 dpc (PubMed:16835393). Expressed in the rostral perichondrial area and mesenchyme of the limb bud in the prospective arm region and hand plate at 10.5 dpc, proximal mesenchyme expression in the forelimb then decreases between 11.5 dpc and 12.5 dpc until expression is consolidated to the arm regions of the developing limb at 12.5 dpc and forelimb digits at 13.5 dpc (PubMed:16835393). Expressed at variable levels in the prospective forebrain to the hindbrain and all neural tube cell layers from 9.5 dpc to postnatal day 6 (P6) (PubMed:16835393, PubMed:26525805). Expressed in immature oligodendrocyte precursor cells and astrocytes at 15.5 dpc, additionally expressed in precursor and differentiating oligodendrocytes in the neural tube from 18.5 dpc to P6 (PubMed:26525805). Highly expressed in embryonic arterial walls at 13.5 dpc (PubMed:9421502). Low levels are found in the inner ear at 13.5 dpc and in some cells in the thymus at 16.5 dpc (PubMed:9421502). Initially expressed in the hair follicles of the whisker pad vibrissae at 14.5 dpc, expression continues in the hair placode and in hair germ and peg during hair follicle morphogenesis to 18 dpc (PubMed:9421502, PubMed:30638933). Expressed in the newborn hair follicle epithelial sheath, this expression weakens at P15, reexpressed in the hair follicle bulge and secondary germ regions at P22, with expression continuing in the root sheath of the hair follicle at P28 (PubMed:30638933). Expressed in trophoblast giant cells of the spongiotrophoblast and labyrinth layers of the placenta at 15.5 dpc (PubMed:16835393). Expressed in DN1d cells, a subset of DN1 precursor thymocytes, from 16 dpc onwards (PubMed:30413363). Expressed in the tracheal epithelium below the vocal cord at 18 dpc (PubMed:9421502). Expression is transiently increased during brown adipocyte differentiation (PubMed:27923061).|||Homodimer; homodimerization reduces DNA binding efficiency (By similarity). Interacts with isoform 2 of TCF7/TCF1 (via N-terminus); inhibits WNT-mediated transcriptional activity (PubMed:17218525). Interacts with HHEX (via N-terminus); abolishes the SOX13-mediated inhibition of WNT-mediated transcriptional activity via competitive inhibition of the SOX13-TCF7 complex (PubMed:20028982).|||Mice show severe growth abnormalities (PubMed:17218525). Severe reduction in the number of Rorc and Vgamma2-positive mature thymocytes in fetal and adult mice caused by the loss of Blk expression in Vgamma2-positive immature thymocytes (PubMed:23562159). This results in a severe reduction of Il17a-producing Vgamma2-positive gamma-delta T-cells in the spleen, lymph nodes and dermis (PubMed:17218525, PubMed:23562159). In addition, the number of Vgamma4-positive thymocytes in the fetal thymus is transiently reduced, with levels returning to normal in neonatal and adult mice (PubMed:23562159). Proliferation of CD3, CD4, and CD8-negative (triple negative) thymocytes and gamma-delta thymocytes is increased (PubMed:17218525). Double knockout of Sox13 and Tcf7/Tcf1 shows a reduced number of DN1d cells (PubMed:30413363). No defects in oligodendrocyte precursor cells specification and in their differentiation into myelinating oligodendrocytes (PubMed:26525805). However, in Sox13 and Sox6 double knockout mice, causes a slight increase in the number of prematurely differentiated oligodendrocytes in the spinal tube compared to Sox6 knockout mice (PubMed:26525805). No defects in the integumentary system morphology and in hair development (PubMed:30638933).|||Nucleus|||Several frameshifts.|||Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3' (PubMed:9524265, PubMed:9421502). Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube (PubMed:26525805). Binds to the gene promoter of MBP and acts as a transcriptional repressor (PubMed:26525805). Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells (PubMed:17218525, PubMed:23562159, PubMed:30413363). Required for the differentiation of Vgamma2-positive gamma-delta T-cells, a subset of IL17A expressing gamma-delta T-cells (PubMed:23562159). Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells (PubMed:23562159). Promotes brown adipocyte differentiation (PubMed:27923061). Inhibitor of WNT signaling (By similarity). http://togogenome.org/gene/10090:Fam228b ^@ http://purl.uniprot.org/uniprot/Q497Q6 ^@ Similarity ^@ Belongs to the FAM228 family. http://togogenome.org/gene/10090:Anp32a ^@ http://purl.uniprot.org/uniprot/O35381 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ANP32 family.|||Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Directly interacts with SET. Interacts with ATXN1/SCA1. Interacts with MAP1B. Interacts with ELAVL1. Part of the INHAT (inhibitor of histone acetyltransferases) complex. Interacts with E4F1.|||Cytoplasm|||Endoplasmic reticulum|||Mice are viable and fertile. They have no derangements in any of the major organ systems, including the nervous systems. Moreover, bone marrow cells from mutant mice only show mild decrease of colony-forming unit(CFU)-myeloid.|||Multifunctional protein that is involved in the regulation of many processes including tumor suppression, apoptosis, cell cycle progression or transcription. Promotes apoptosis by favouring the activation of caspase-9/CASP9 and allowing apoptosome formation. In addition, plays a role in the modulation of histone acetylation and transcription as part of the INHAT (inhibitor of histone acetyltransferases) complex. Inhibits the histone-acetyltranferase activity of EP300/CREBBP (CREB-binding protein) and EP300/CREBBP-associated factor by histone masking. Preferentially binds to unmodified histone H3 and sterically inhibiting its acetylation and phosphorylation leading to cell growth inhibition (PubMed:29467488). Participates in other biochemical processes such as regulation of mRNA nuclear-to-cytoplasmic translocation and stability by its association with ELAVL1 (Hu-antigen R). Plays a role in E4F1-mediated transcriptional repression as well as inhibition of protein phosphatase 2A (By similarity) (PubMed:17557114, PubMed:29467488).|||Nucleus|||Phosphorylated on serine residues, at least in part by casein kinase 2/CK2.|||Predominantly expressed in the cerebellum. Expressed also in cortex, lung, skeletal muscle, gastrointestinal tract, spleen, liver and heart.|||Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group. http://togogenome.org/gene/10090:Vmn1r194 ^@ http://purl.uniprot.org/uniprot/J3JS27 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Steap1 ^@ http://purl.uniprot.org/uniprot/Q3UNB9|||http://purl.uniprot.org/uniprot/Q9CWR7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STEAP family.|||Cell membrane|||Does not function as a metalloreductase due to the absence of binding sites for the electron-donating substrate NADPH.|||Endosome membrane|||Homotrimer.|||Membrane http://togogenome.org/gene/10090:Epb41l4b ^@ http://purl.uniprot.org/uniprot/Q9JMC8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in mouse liver cells, with lower amounts in lung, kidney and in 7- to 17-day embryos. Expression not detected in adult mouse heart, brain, spleen, skeletal muscle or testis.|||Interacts (via FERM domain) with ARHGEF18 (via C-terminus); the interaction activates ARHGEF18.|||May be negatively regulated by phosphorylation.|||Up-regulates the activity of the Rho guanine nucleotide exchange factor ARHGEF18 (PubMed:22006950). Involved in the regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950). Promotes cellular adhesion, migration and motility in vitro and may play a role in wound healing (By similarity). May have a role in mediating cytoskeletal changes associated with steroid-induced cell differentiation (By similarity).|||tight junction http://togogenome.org/gene/10090:Tbk1 ^@ http://purl.uniprot.org/uniprot/A1L361|||http://purl.uniprot.org/uniprot/Q9WUN2 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Lys-63'-linked polyubiquitination by MIB1 after RNA virus infection, or by NRDP1 after LPS stimulation at Lys-30 and Lys-401, participates in kinase activation. 'Lys-48'-linked polyubiquitination at Lys-670 by DTX4 leads to proteasomal degradation. 'Lys-48'-linked polyubiquitination by TRAIP also leads to proteasomal degradation. 'Lys-48'-linked polyubiquitination by TRAF7; leading to proteasomal degradation. 'Lys-63'-linked polyubiquitination by RNF128 at Lys-30 and Lys-401 leads to the activation of antiviral responses. 'Lys-48'-linked polyubiquitination after 'lys-33'-linked deubiquitination by USP38 promotes TBK1 degradation.|||Autophosphorylation at Ser-172 activates the kinase, and is an essential step for virus-triggered signaling. Phosphorylated by IKBKB/IKKB at Ser-172. Phosphorylation requires homodimerization and ubiquitination at Lys-30 and Lys-401. Dephosphorylated at Ser-172 by PPM1B and this negatively regulates its role in mediating antiviral response.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.|||Comprises A N-terminal kinase domain, a ubiquitin-like domain and a C-terminal coiled-coil region mediating homodimerization.|||Cytoplasm|||Homodimer (PubMed:23746807). Interacts with DDX3X, TIRAP and TRAF2 (By similarity). Part of a ternary complex consisting of TANK, TRAF2 and TBK1 (By similarity). Interacts with AZI2, TANK and TBKBP1; these interactions are mutually exclusive and mediate TBK1 activation (By similarity). Interacts with GSK3B; this interaction promotes TBK1 self-association and autophosphorylation (By similarity). Interacts with SIKE1; SIKE1 is associated with TBK1 under physiological condition and dissociated from TBK1 upon viral infection or TLR3 stimulation (By similarity). Interacts with IRF3, leading to IRF3 phosphorylation (By similarity). Interacts with RIGI (By similarity). Interacts with CYLD (By similarity). Interacts with OPTN and TRAF3 (By similarity). Interacts with SRC (By similarity). Interacts with the exocyst complex subunit SEC5/EXOC2; this interaction is sufficient to trigger TBK1 activity (By similarity). Interacts with STING1, leading to STING1 phosphorylation (By similarity). Interacts with IFIT3 (via N-terminus) (By similarity). Interacts with MAVS; interaction only takes place in the presence of IFIT3 and leads to MAVS phosphorylation (By similarity). Interacts (via protein kinase domain) with TTLL12 (via TTL domain); the interaction prevents MAVS binding to TBK1 (By similarity). Interacts with TICAM1; this interaction is enhanced in the presence of WDFY1 and leads to TICAM1 phosphorylation (By similarity). Interacts with TRIM26 (By similarity). Interacts with TRIM23 (By similarity). Interacts with TTC4 and IKBKE (By similarity). Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with DDX3X (By similarity). Interacts with TRIM14 (By similarity). Interacts with CEP170; efficient complex formation may be dependent on the presence of CCDC61 (By similarity). Interacts with TRAF3IP3 (By similarity). Interacts with HSP90AA1; the interaction mediates TBK1 association with TOMM70 (By similarity). Interacts with TAX1BP1 (By similarity).|||Kinase activity is inhibited competitively by amlexanox.|||Mice display embryonic lethality at 14.5 dpc due to massive liver degeneration and apoptosis. Embryonic fibroblasts from mice lacking Tbk1 exhibit dramatically reduced transcription of NF-kappa-B, as well as marked defects in interferon alpha and beta, and RANTES gene expression after infection with Sendai or Newcastle disease virus.|||Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:15210742, PubMed:15661922). Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X (By similarity). This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB (By similarity). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (By similarity). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (By similarity). Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (By similarity). Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus (By similarity). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (By similarity). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (By similarity). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (By similarity). Phosphorylates and activates AKT1 (By similarity). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity (PubMed:23396211). http://togogenome.org/gene/10090:Mtrf1l ^@ http://purl.uniprot.org/uniprot/Q8BJU9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the prokaryotic/mitochondrial release factor family.|||Methylation of glutamine in the GGQ triplet by HEMK1 is conserved from bacteria to mammals.|||Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain termination codons UAA and UAG.|||Mitochondrion|||The GGQ domain interacts with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis. http://togogenome.org/gene/10090:Etnk2 ^@ http://purl.uniprot.org/uniprot/A7MCT6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ According to PubMed:16861741, disruption of the gene causes increased prevalence of placental thrombosis, reduced litter size and increased pup mortality. No such effect was observed by PubMed:18755794. One possible explanation lies in the fact that PubMed:16861741 observed a remarkable 100% survival of control pups and 16% mortality for mutant pups, while PubMed:18755794 observed 16% mortality for both wild-type and mutant pups. According to PubMed:18755794, the construct used in PubMed:16861741 may lead to expression of a truncated transcript that might have deleterious effects.|||Belongs to the choline/ethanolamine kinase family.|||Expressed in testis and liver. Low expression in ovary and kidney.|||Highly specific for ethanolamine phosphorylation. Does not have choline kinase activity.|||No visible phenotype in adults. No significant effect is seen on liver phospholipid metabolism, neural development, or testicular function. No abnormalities are detected in embryonic and adult testis morphology, differentiation, function, or fertility. PubMed:16861741 shows maternal-specific failure to support late embryonic development, resulting in reduced perinatal size and survival and suggesting compromised placental function.|||The expression is restricted to the gonads during the sex determination period and throughout embryogenesis. In developing testis, the expression is found only in the Sertoli cells. The expression is strongest at day 11.5, more intense in the testis than the ovary. From 12.5 dpc the expression in the ovary is reduced and disappears. The expression at day 13.5 dpc is restricted to the testis cords. http://togogenome.org/gene/10090:Atxn2 ^@ http://purl.uniprot.org/uniprot/E9QM77|||http://purl.uniprot.org/uniprot/O70305 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ataxin-2 family.|||Cytoplasm|||Detectable at 8-16 dpc. Lowest expression was seen at 8 dpc.|||Expressed in the heart, lung, liver, kidney, skeletal muscle, spleen and intestine. Predominant expression was seen in the brain where a high level expression was found in the pyramidal cortical neurons, large brain stem neurons and cerebellar Purkinje cells. All three isoforms were found in all the tissues except skeletal muscle where only isoform 1 was found.|||Interacts with RBFOX1 (By similarity). Monomer. Can also form homodimers. Interacts with polyribosomes (By similarity). Interacts with EGFR (By similarity). Interacts with SH3GL3 (By similarity). Interacts with SH3GL2, SH3KBP1 and CBL (PubMed:18602463). Interacts with ATXN2L (By similarity).|||Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. http://togogenome.org/gene/10090:Apol7a ^@ http://purl.uniprot.org/uniprot/B2RT54|||http://purl.uniprot.org/uniprot/Q8BUC6|||http://purl.uniprot.org/uniprot/Q9D2Y0 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Or5d35 ^@ http://purl.uniprot.org/uniprot/Q7TR29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5t5 ^@ http://purl.uniprot.org/uniprot/Q8VF14 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wnk2 ^@ http://purl.uniprot.org/uniprot/E9QM73|||http://purl.uniprot.org/uniprot/E9QMI8|||http://purl.uniprot.org/uniprot/E9QMI9|||http://purl.uniprot.org/uniprot/Q3UH66 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation requires autophosphorylation of Ser-356 and, to a lower extent, Ser-352 (By similarity).|||Autophosphorylated (By similarity). Autophosphorylation at Ser-352 and Ser-356 promotes its activity (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.|||Brain and heart.|||Cell membrane|||Cytoplasm|||Forms a complex with the phosphorylated form of STK39 in the brain.|||Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (By similarity). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (By similarity). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (By similarity).|||Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins. http://togogenome.org/gene/10090:Tnnc1 ^@ http://purl.uniprot.org/uniprot/P19123 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the troponin C family.|||Cardiac muscle Tn-C can bind 3 calcium ions per molecule. Domain I does not bind calcium.|||Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments. http://togogenome.org/gene/10090:Dpp7 ^@ http://purl.uniprot.org/uniprot/Q9ET22 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S28 family.|||Cytoplasmic vesicle|||Homodimer.|||Lysosome|||Plays an important role in the degradation of some oligopeptides.|||Secreted http://togogenome.org/gene/10090:Taf1a ^@ http://purl.uniprot.org/uniprot/B9EHT7|||http://purl.uniprot.org/uniprot/P97357 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits.|||Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits. Interacts with UBFT (By similarity). Interacts with CEBPA (isoform 1 and isoform 4) (By similarity).|||Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits (By similarity).|||Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.|||Nucleus http://togogenome.org/gene/10090:Gstm6 ^@ http://purl.uniprot.org/uniprot/O35660 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Cytoplasm|||Expressed in liver, stomach and small intestine. Not expressed in spleen, kidney, colon, heart, muscle, brain or lung.|||Homodimer. http://togogenome.org/gene/10090:Acot12 ^@ http://purl.uniprot.org/uniprot/Q9DBK0 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Subunit ^@ Allosterically regulated by ATP (activator) and ADP (inhibitor) (By similarity). Cold labile, it dissociates into inactive monomers at low temperature (By similarity).|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Preferentially hydrolyzes acetyl-CoA.|||Homodimer or homotetramer.|||cytosol http://togogenome.org/gene/10090:Rnf115 ^@ http://purl.uniprot.org/uniprot/Q9D0C1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin-protein ligase that mediates E2-dependent, 'Lys-48'- and/or 'Lys-63'-linked polyubiquitination of substrates and may play a role in diverse biological processes. Through their polyubiquitination, may play a role in the endosomal trafficking and degradation of membrane receptors including EGFR, FLT3, MET and CXCR4.|||Interacts with RAB7A. Interacts with EGFR and FLT3.|||RING-type zinc finger-dependent and E2-dependent autoubiquitination.|||cytosol http://togogenome.org/gene/10090:Vmn1r70 ^@ http://purl.uniprot.org/uniprot/Q8R254 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhox3c ^@ http://purl.uniprot.org/uniprot/A2AWM0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Stub1 ^@ http://purl.uniprot.org/uniprot/Q9WUD1 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated; mediated by UBE2D1 and UBE2D2. Monoubiquitinated at Lys-2 following cell stress by UBE2W, promoting the interaction with ATXN3.|||Cytoplasm|||E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation (PubMed:11435423, PubMed:21855799). Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (PubMed:11435423, PubMed:21855799). Ubiquitinates NOS1 in concert with Hsp70 and Hsp40 (By similarity). Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90 (By similarity). Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation (By similarity). Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome (By similarity). Mediates polyubiquitination of CYP3A4 (By similarity). Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation (By similarity). Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin-mediated protein degradation. Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner (PubMed:23973223). Catalyzes monoubiquitination of SIRT6, preventing its degradation by the proteasome (PubMed:24043303). Likely mediates polyubiquitination and down-regulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity (By similarity). Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (By similarity). May regulate myosin assembly in striated muscles together with UBE4B and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (By similarity). Mediates ubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation (By similarity).|||Homodimer (PubMed:16307917). Interacts with BAG2, and with the E2 ubiquitin conjugating enzymes UBE2D1, UBE2D2 and UBE2D3. Detected in a ternary complex containing STUB1, HSPA1A and HSPBP1. Interacts with MKKS. Interacts with DNAAF4 (By similarity). Interacts (via the U-box domain) with the UBE2V2-UBE2N heterodimer; the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts (when monoubiquitinated) with ATXN3 (PubMed:21855799). Interacts with UBE2W (PubMed:21855799). Interacts with DNAJB6 (By similarity). Interacts with FLCN and HSP90AA1. Interacts with HSP90. Interacts with UBE2N and UBE2V1. Interacts (via TPR repeats) with the C-terminal domains of HSPA8 and HSPA1A. Interacts with the non-acetylated form of HSPA1A and HSPA1B. Interacts with SMAD3 and HSP90AB1 (By similarity). Interacts with UBE4B (By similarity). Interacts with PRMT5 (By similarity).|||Nucleus|||The TPR domain is essential for ubiquitination mediated by UBE2D1.|||The U-box domain is required for the ubiquitin protein ligase activity.|||Up-regulated by inflammatory signals in Treg regulatory T-cells (Treg). http://togogenome.org/gene/10090:Mcam ^@ http://purl.uniprot.org/uniprot/Q8R2Y2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in melanoma cell lines.|||Membrane|||Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration (By similarity). http://togogenome.org/gene/10090:Ythdf2 ^@ http://purl.uniprot.org/uniprot/Q91YT7 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YTHDF family. YTHDF2 subfamily.|||Expressed in the germline during gametogenesis: expressed at all stages of spermatogenesis, with elevated expression observed in pachytene spermatocytes (PubMed:28867294). During oogenesis, expressed at all stages of folliculogenesis: expressed both in the oocyte and in somatic granulosa cells (PubMed:28867294). Also expressed during oocyte maturation, with abundant expression in germinal vesicle as well as in meiosis II oocytes (PubMed:28867294).|||Female are infertile despite successful ovulation (PubMed:28867294, PubMed:32943573). Corpora lutea is present in ovaries, indicating that ovulation has occurred (PubMed:28867294). Defects during oocyte maturation are probably caused by the deregulation of some transcripts, leading to an arrest prior to or at the two-cell stage, with various cytokinesis defects observed in the two-cell embryos (PubMed:28867294). Males are hypofertile because of mild degenerative changes in the seminiferous tubules, including large scattered vacuoles in Sertoli cells and severe loss of sperm in the cauda epididymis (PubMed:32943573). Conditional deletion in embryos leads to lethality at late embryonic developmental stages, caused by defects in neural development (PubMed:29855337). Conditional deletion in spermatogonia leads to impaired spermatogonial proliferation caused by decreased cell spread (PubMed:31959747). The proliferation and differentiation capabilities of neural stem/progenitor cell (NSPC) decrease significantly in conditional deletion mutant embryos (PubMed:29855337). Conditional deletion in hematopoietic stem cells promotes hematopoietic stem cell expansion (PubMed:30065315, PubMed:30150673). Mice lacking Ythdf1, Ythdf2 and Ythdf3 display early embryonic lethality and show defects in embryonic stem cell differentiation (PubMed:32943573).|||Interacts with CNOT1; interaction is direct and promotes recruitment of the CCR4-NOT complex (PubMed:32905781). Interacts with YTHDF3 (By similarity). Interacts with RIDA/HRSP12; interaction leads to recruitment of the ribonuclease P/MRP complex (By similarity).|||Nucleus|||P-body|||Previous studies suggested the 3 different paralogs (YTHDF1, YTHDF2 and YTHDF3) have unique functions with limited redundancy (By similarity). However, later studies showed that YTHDF1, YTHDF2 and YTHDF3 paralogs have redundant functions to a profound extent and directly promote degradation of m6A-containing mRNAs (PubMed:32943573).|||Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:28867294, PubMed:29855337, PubMed:32943573). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:28867294, PubMed:29855337, PubMed:32943573). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:29855337, PubMed:30065315, PubMed:32943573, PubMed:32905781). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:32943573). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (By similarity). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:32905781). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (PubMed:28867294). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (PubMed:31959747). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315, PubMed:30150673). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (PubMed:29855337). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (By similarity). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (By similarity). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (By similarity). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (By similarity). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (By similarity). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (By similarity). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (By similarity).|||Stress granule|||The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons.|||Ubiquitinated by the SCF(SKP2) complex, leading to its degradation.|||Widely expressed, with highest expression in testis.|||cytosol http://togogenome.org/gene/10090:Ube2l3 ^@ http://purl.uniprot.org/uniprot/P68037|||http://purl.uniprot.org/uniprot/Q561N4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Cytoplasm|||In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119, respectively.|||Interacts with PRKN; involved in ubiquitination and degradation of misfolded proteins. Interacts with UBE3A. Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; they functionally interact to regulate progesterone receptor transcriptional activity. Interacts with NDFIP1 (via N-terminus); the interaction mediates recruitment of UBE2L3 to ITCH and causes MAP3K7 ubiquitination (PubMed:25632008).|||Nucleus|||Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN, RNF31 and ARIH1, that function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis.|||Ubiquitinated. The alteration of UBE2L3 protein levels during the S-phase of the cell cycle is due to ubiquitin-dependent proteasomal degradation. Autoubiquitinated in vitro. http://togogenome.org/gene/10090:Slc22a2 ^@ http://purl.uniprot.org/uniprot/O70577 ^@ Activity Regulation|||Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basal cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is required for the activation of substrate transport.|||Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:23458604). Functions as a Na(+)-independent, bidirectional uniporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (By similarity). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow. Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters. Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system. Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium. Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN). Mediates the uptake and efflux of quaternary ammonium compound choline (By similarity). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:23458604). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity).|||Expressed in kidney and ureter (PubMed:10051314, PubMed:26979622). To a lower extent, also expressed in brain and embryo (PubMed:10051314).|||Mediates the renal secretion of many clinically used cationic drugs (PubMed:23458604) (By similarity). Transports drugs such as diabetes treatment medicine metformin and neurotoxins 1-methyl-4-phenylpyridinium (MPP(+)), famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine, cimetidine, cisplatin, oxaliplatin, platinum-based drugs cisplatin and oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and tetraethylammonium (TEA) (PubMed:23458604). Mediates the bidirectional transport of MPP(+). Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis. Plays a predominant role in the anticancer activity of cisplatin and oxaliplatin and may contribute to antitumor specificity (By similarity). Involved in cisplatin-induced nephrotoxicity (By similarity).|||Tyrosine phosphorylated by tyrosine-protein kinase YES1.|||Tyrosine phosphorylation of the transporter leads to activation of the transport activity (PubMed:26979622). TEA uptake is activated by tyrosine phosphorylation (PubMed:26979622). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2 (By similarity).|||While most authors have deduced a localization at the basolateral membrane of proximal tubules, other studies demonstrated a localization to the luminal membrane in the distal tubule. http://togogenome.org/gene/10090:Gstm4 ^@ http://purl.uniprot.org/uniprot/A2AE91|||http://purl.uniprot.org/uniprot/Q8R5I6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4. Can also catalyze the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions.|||Cytoplasm|||Homodimer.|||Widely expressed. http://togogenome.org/gene/10090:Nfya ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Y8|||http://purl.uniprot.org/uniprot/P23708|||http://purl.uniprot.org/uniprot/Q3UP82|||http://purl.uniprot.org/uniprot/Q9DBV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NFYA/HAP2 subunit family.|||Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes.|||Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component BMAL1.|||Heterotrimer.|||Heterotrimeric transcription factor composed of three components, NF-YA, NF-YB and NF-YC. NF-YB and NF-YC must interact and dimerize for NF-YA association and DNA binding (By similarity). Interacts with SP1; the interaction is inhibited by glycosylation of SP1. Interacts (via N-terminus) with ZHX2 (via homeobox domain). Interacts with ZFX3. Interacts with ZHX1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm21244 ^@ http://purl.uniprot.org/uniprot/J3QK38 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or56a3 ^@ http://purl.uniprot.org/uniprot/Q8VGV0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zbtb14 ^@ http://purl.uniprot.org/uniprot/Q08376 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with ZBTB21.|||Nucleus|||The BTB/POZ domain seems to direct the protein to discrete regions in the nucleus.|||Transcriptional activator of the dopamine transporter (DAT), binding it's promoter at the consensus sequence 5'-CCTGCACAGTTCACGGA-3'. Binds to 5'-d(GCC)(n)-3' trinucleotide repeats in promoter regions and acts as a repressor of the FMR1 gene (By similarity). Transcriptional repressor of MYC and thymidine kinase promoters.|||Ubiquitous. http://togogenome.org/gene/10090:Washc3 ^@ http://purl.uniprot.org/uniprot/G3UWG7|||http://purl.uniprot.org/uniprot/Q9CR27|||http://purl.uniprot.org/uniprot/Q9CYF6|||http://purl.uniprot.org/uniprot/S4R287 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sortingg.|||Belongs to the CCDC53 family.|||Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5. The WASH core complex associates via WASHC2 with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex.|||Early endosome http://togogenome.org/gene/10090:Srr ^@ http://purl.uniprot.org/uniprot/Q9QZX7 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP.|||Belongs to the serine/threonine dehydratase family.|||Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine.|||Detected in brain (at protein level). Brain.|||Homodimer.|||S-nitrosylated, leading to decrease the enzyme activity. http://togogenome.org/gene/10090:Ddost ^@ http://purl.uniprot.org/uniprot/O54734 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DDOST 48 kDa subunit family.|||Component of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (By similarity). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes. Interacts with SMIM22 (By similarity).|||Endoplasmic reticulum membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (By similarity). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes (By similarity). http://togogenome.org/gene/10090:Or7g20 ^@ http://purl.uniprot.org/uniprot/Q7TRG7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vps13d ^@ http://purl.uniprot.org/uniprot/B1ART2|||http://purl.uniprot.org/uniprot/Q6A066 ^@ Similarity ^@ Belongs to the VPS13 family. http://togogenome.org/gene/10090:Ndufb7 ^@ http://purl.uniprot.org/uniprot/Q9CR61 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB7 subunit family.|||Complex I is composed of 45 different subunits.|||Contains two C-X9-C motifs that are predicted to form a helix-coil-helix structure, permitting the formation of intramolecular disulfide bonds.|||Mitochondrion inner membrane|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Set ^@ http://purl.uniprot.org/uniprot/Q3T9S3|||http://purl.uniprot.org/uniprot/Q9EQU5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A long alpha helix in the N-terminus mediates dimerization, while the earmuff domain is responsible for core histone and dsDNA binding. The C-terminal acidic domain mediates the inhibition of histone acetyltransferases and is required for the DNA replication stimulatory activity (By similarity).|||Belongs to the nucleosome assembly protein (NAP) family.|||Cleaved after Lys-176 by GZMA. The cleavage inhibits its nucleosome assembly activity and disrupts the inhibition on NME1 (By similarity).|||Endoplasmic reticulum|||Headphone-shaped homodimer. Isoform 1 and isoform 2 interact directly with each other and with ANP32A within the tripartite INHAT (inhibitor of acetyltransferases) complex. Isoform 1 and isoform 2 interact also with histones. Isoform 2 is a omponent of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1, but not NME2 or TREX2. Within this complex, directly interacts with ANP32A, NME1, HMGB2 and TREX1; the interaction with ANP32A is enhanced after cleavage. Interacts with APBB1, CHTOP, SETBP1, SGO1.|||Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning. Isoform 2 anti-apoptotic activity is mediated by inhibition of the GZMA-activated DNase, NME1. In the course of cytotoxic T-lymphocyte (CTL)-induced apoptosis, GZMA cleaves SET, disrupting its binding to NME1 and releasing NME1 inhibition. Isoform 1 and isoform 2 are potent inhibitors of protein phosphatase 2A. Isoform 1 and isoform 2 inhibit EP300/CREBBP and PCAF-mediated acetylation of histones (HAT) and nucleosomes, most probably by masking the accessibility of lysines of histones to the acetylases. The predominant target for inhibition is histone H4. HAT inhibition leads to silencing of HAT-dependent transcription and prevents active demethylation of DNA. Both isoforms stimulate DNA replication of the adenovirus genome complexed with viral core proteins; however, isoform 2 specific activity is higher (By similarity).|||N-terminus of isoform 1 is methylated by METTL11A/NTM1. Mainly trimethylated.|||Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group.|||cytosol|||nucleoplasm http://togogenome.org/gene/10090:Adam26a ^@ http://purl.uniprot.org/uniprot/Q8BMR4|||http://purl.uniprot.org/uniprot/Q9R158 ^@ Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Adult expression levels are reached by day 25 after birth.|||Binds 1 zinc ion per subunit.|||Expressed in sperm (at protein level) (PubMed:20945367). Expressed specifically in testis (PubMed:10395895).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Sperm surface membrane protein that may be involved in spermatogenesis and fertilization.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme. http://togogenome.org/gene/10090:Sarnp ^@ http://purl.uniprot.org/uniprot/Q9D1J3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway (By similarity).|||Interacts with DDX39A. Interacts with FUS. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have dynamic structure involving ATP-dependent remodeling; in the complex interacts directly with DDX39B in a ATP-dependent manner which bridges it to ALYREF/THOC4 (By similarity).|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Dnal1 ^@ http://purl.uniprot.org/uniprot/Q05A62 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein light chain LC1-type family.|||Expressed in the respiratory epithelium of the upper airways and the ependymal cells lining the brain ventricles.|||Interacts with ZMYND10 (via C-terminus). Interacts with DNAH5, a outer arm dynein heavy chain. Interacts with tubulin located within the A-tubule of the outer doublets in a ATP-independent manner.|||Outer (ODAs) and inner (IDAs) dynein arms contain the molecular motors that generate the force to move cilia by ATP-dependent reactions. There are two mechanosensory systems that monitor and respond to the mechanical state (curvature) of the axoneme. One system involves the central pair microtubule complex and radial spokes and the second system involves the outer dynein arms.|||Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency (By similarity). Component of the outer arm dynein (ODA). May be involved in a mechanosensory feedback mechanism controlling ODA activity based on external conformational cues by tethering the outer arm dynein heavy chain (DNAH5) to the microtubule within the axoneme (By similarity). Important for ciliary function in the airways and for the function of the cilia that produce the nodal flow essential for the determination of the left-right asymmetry (By similarity).|||cilium axoneme http://togogenome.org/gene/10090:Gm4981 ^@ http://purl.uniprot.org/uniprot/Q3ULJ8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Fbxo22 ^@ http://purl.uniprot.org/uniprot/Q78JE5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes the proteasome-dependent degradation of key sarcomeric proteins, such as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for maintenance of normal contractile function.|||Z line http://togogenome.org/gene/10090:Mfsd6l ^@ http://purl.uniprot.org/uniprot/Q8R3N2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. MFSD6 family.|||Membrane http://togogenome.org/gene/10090:Izumo1r ^@ http://purl.uniprot.org/uniprot/Q8BUM2|||http://purl.uniprot.org/uniprot/Q8BY83|||http://purl.uniprot.org/uniprot/Q9EQF4 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the folate receptor family.|||Cell membrane|||Female mice are infertile and eggs do not fuse with normal sperm (PubMed:24739963). Both male and female mice develop normally and are overtly healthy (PubMed:24739963). Male mice are fertile (PubMed:24739963). Despite infertility, female mice display natural mating behaviors, as assessed by vaginal plug formation and the presence of motile sperm in the reproductive tract when paired with fertile males (PubMed:24739963). They respond to hormone treatment by ovulating morphologically normal eggs at numbers that do not significantly differ from wild-type (PubMed:24739963). However, eggs are not fertilized and have more sperm within their perivitelline space compared to wild-type eggs, demonstrating that the zona pellucida of eggs cannot be penetrated by sperm in vivo (PubMed:24739963).|||In contrast to FOLR1 and FOLR2, unable to bind folate.|||Monomer (PubMed:26859261). Interacts with IZUMO1; the interaction is direct (PubMed:24739963, PubMed:26859261, PubMed:27309808, PubMed:25209248, PubMed:27416963, PubMed:32484434). IZUMO1 and IZUMO1R/JUNO form a complex with 1:1 stoichiometry (By similarity).|||Receptor for IZUMO1 present at the cell surface of oocytes (oolemma), which is essential for species-specific gamete recognition and fertilization (PubMed:24739963, PubMed:26859261, PubMed:27309808, PubMed:27416963). The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion (PubMed:24739963, PubMed:26859261, PubMed:27309808). The ligand-receptor interaction probably does not act as a membrane 'fusogen' (PubMed:24739963, PubMed:26859261, PubMed:27309808). Does not bind folate (PubMed:24739963).|||The protein is rapidly cleaved following fertilization, being only weakly detectable in zona-intact fertilized eggs at telophase II and undetectable at the pronuclear stage (PubMed:24739963). Sheding is probably required to block to polyspermy and ensuring egg fusion with a single sperm (PubMed:24739963).|||Was named 'Juno' after the Roman goddess of fertility and marriage.|||Widely expressed with higher expression in thymus, spleen and lung (PubMed:11111049). Present at the cell surface of unfertilized oocytes, while it is barely detectable 30 to 40 minutes after fertilization (at protein level) (PubMed:24739963). http://togogenome.org/gene/10090:Nsf ^@ http://purl.uniprot.org/uniprot/P46460 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Homohexamer. Interacts with GABARAP and GABARAPL2. Interacts with GRIA2. Interacts with PLK2, leading to disrupt the interaction with GRIA2. Interacts with MUSK; may regulate MUSK endocytosis and activity (By similarity). Interacts with CDK16.|||Phosphorylation at Ser-569 interferes with homohexamerization.|||Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seems to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack GRIA2 leads to influence GRIA2 membrane cycling (By similarity). http://togogenome.org/gene/10090:Tdpoz1 ^@ http://purl.uniprot.org/uniprot/P0DMR5|||http://purl.uniprot.org/uniprot/Q05AE5 ^@ Developmental Stage|||Similarity ^@ Belongs to the Tdpoz family.|||Expressed in unfertilized eggs and pre-implantation embryos. Undetectable in later-stage fetuses or in adult tissues. http://togogenome.org/gene/10090:Adtrp ^@ http://purl.uniprot.org/uniprot/A0A0R4J0W3|||http://purl.uniprot.org/uniprot/Q8C138 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AIG1 family.|||Cell membrane|||Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids (By similarity). Shows a preference for FAHFAs with branching distal from the carboxylate head group of the lipids (By similarity). Regulates the expression and the cell-associated anticoagulant activity of the inhibitor TFPI in endothelial cells (in vitro) (By similarity).|||Membrane http://togogenome.org/gene/10090:Cnn2 ^@ http://purl.uniprot.org/uniprot/Q08093|||http://purl.uniprot.org/uniprot/Q543F3 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the calponin family.|||Smooth muscle, and tissues containing significant amounts of smooth muscle.|||Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity. http://togogenome.org/gene/10090:Saysd1 ^@ http://purl.uniprot.org/uniprot/Q8K190 ^@ Subcellular Location Annotation ^@ Cytoplasmic vesicle membrane http://togogenome.org/gene/10090:Nptxr ^@ http://purl.uniprot.org/uniprot/A0A9R1SP20|||http://purl.uniprot.org/uniprot/Q6PD36 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Snrnp48 ^@ http://purl.uniprot.org/uniprot/Q9D361 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Not found in the major spliceosome (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Likely involved in U12-type 5' splice site recognition.|||Nucleus|||The CHHC region interacts with the 5' splice site of the U12-type Intron. http://togogenome.org/gene/10090:Sva ^@ http://purl.uniprot.org/uniprot/Q3SXH3 ^@ Similarity|||Subunit ^@ Belongs to the PIP family.|||Monomer. Interacts with AZGP1. http://togogenome.org/gene/10090:Rb1cc1 ^@ http://purl.uniprot.org/uniprot/Q9ESK9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed from an early stage of the embryo throughout development. Ubiquitously expressed, especially in the musculoskeletal system, heart and neural tissues.|||Cytoplasm|||Expressed abundantly in heart and testis, and moderately in kidney, liver and skeletal muscles. Very low expression levels in lung and spleen. Colocalizes with RB1 in various tissues.|||Involved in autophagy (PubMed:23262492, PubMed:19258318). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225, PubMed:23285000, PubMed:19258318). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (PubMed:21525242). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (PubMed:21807966). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (By similarity). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (PubMed:21795712). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:15968549). Plays a crucial role in muscular differentiation (PubMed:15968549). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (PubMed:19940130, PubMed:21088496).|||Lysosome|||Nucleus|||Part of a complex containing ATG13/KIAA0652, ULK1 and RB1CC1 (PubMed:19258318). This complex associates with ATG101 (By similarity). Interacts with PTK2/FAK1 and PTK2B/PYK2 (By similarity). Interacts with GABARAP and GABARAPL1 (By similarity). Interacts with ATG16L1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:23392225, PubMed:23262492). Interacts with RNF111, SKI and SMAD7 (PubMed:21795712). Interacts with COP1 in the cytoplasm of proliferating cells in response to UV stimulation (By similarity). Interacts with TP53 (By similarity). Interacts with C9orf72 (By similarity). Interacts with WDR45B (PubMed:28561066). Interacts with ATG13; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with WIPI2 (By similarity). Interacts with TAX1BP1 (By similarity). Interacts (via phosphorylated FFAT motif) with MOSPD2 (By similarity).|||Phosphorylation at Ser-733 of the FFAT motif activates interaction with MOSPD2.|||Preautophagosomal structure|||The FFAT motif is involved in the interaction with MOSPD2 and its phosphorylation regulates this interaction.|||cytosol http://togogenome.org/gene/10090:Nubp2 ^@ http://purl.uniprot.org/uniprot/Q9R061 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.|||Binds 4 [4Fe-4S] clusters per heterotetramer. Contains two stable clusters in the N-termini of NUBP1 and two labile, bridging clusters between subunits of the NUBP1-NUBP2 heterotetramer.|||Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The NUBP1-NUBP2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins. Negatively regulates cilium formation and structure (PubMed:23807208).|||Cytoplasm|||Expressed at 7, 11, 15 and 17 dpc.|||Heterotetramer of 2 NUBP1 and 2 NUBP2 chains (By similarity). Interacts with KIFC1 (PubMed:16638812). Interacts with NUBP1 (PubMed:16638812, PubMed:23807208).|||Nucleus|||Widely expressed.|||centriole|||centrosome|||cilium axoneme|||microtubule organizing center http://togogenome.org/gene/10090:Lap3 ^@ http://purl.uniprot.org/uniprot/Q9CPY7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M17 family.|||Binds two metal ions per subunit. Two metal binding sites with different affinities are located in the enzyme active site and can be occupied in vitro by different metals: site 1 is occupied by Zn(2+), Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be occupied by only Zn(2+) or Co(2+). One Zn(2+) ion is tightly bound to site 2 and essential for enzyme activity in vivo, while site 1 can be occupied by different metals to give different enzymatic activities. Mn(2+) is required for Cys-Gly hydrolysis activity. A third metal binding site may serve a structural role, possibly stabilizing part of the interface between the N-terminal and the catalytic domain.|||Cytoplasm|||Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status.|||Homohexamer. http://togogenome.org/gene/10090:Cav2 ^@ http://purl.uniprot.org/uniprot/Q924U4|||http://purl.uniprot.org/uniprot/Q9WVC3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the caveolin family.|||Cell membrane|||Cytoplasm|||Golgi apparatus membrane|||May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity.|||May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity).|||Membrane|||Monomer or homodimer. Interacts with CAV1; the interaction forms a stable heterooligomeric complex that is required for targeting to lipid rafts and for caveolae formation. Tyrosine phosphorylated forms do not form heterooligomers with the Tyr-19-phosphorylated form existing as a monomer or dimer, and the Tyr-27-form as a monomer only. Interacts (tyrosine phosphorylated form) with the SH2 domain-containing proteins, RASA1, NCK1 and SRC. Interacts (tyrosine phosphorylated form) with INSR, the interaction (Tyr-27-phosphorylated form) is increased on insulin stimulation. Interacts (Tyr-19 phosphorylated form) with MAPK1 (phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with STAT3; the interaction is increased on insulin-induced tyrosine phosphorylation leading to STAT activation (By similarity).|||Nucleus|||Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears to modulate mitosis in endothelial cells. Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-induced 'Ser-727' phosphorylation of STAT3 and its activation. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin (By similarity).|||caveola http://togogenome.org/gene/10090:Cd5 ^@ http://purl.uniprot.org/uniprot/P13379|||http://purl.uniprot.org/uniprot/Q3UP78 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with CD72/LYB-2. Interacts with PTPN6/SHP-1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May act as a receptor in regulating T-cell proliferation.|||Phosphorylated on tyrosine residues by LYN; this creates binding sites for PTPN6/SHP-1. http://togogenome.org/gene/10090:Scgb2b21 ^@ http://purl.uniprot.org/uniprot/A0A087WQA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Aldoc ^@ http://purl.uniprot.org/uniprot/P05063 ^@ Developmental Stage|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the class I fructose-bisphosphate aldolase family.|||Expressed exclusively in Purkinje cells in bands running from anterior to posterior across most of the cerebellum. Expressed at higher levels in the brains of BSE-infected animals.|||Expression begins in the first week of postnatal life.|||Homotetramer. Interacts with ATP6V1E1 (By similarity).|||In vertebrates, three forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain. http://togogenome.org/gene/10090:Pramel7 ^@ http://purl.uniprot.org/uniprot/Q810Y8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PRAME family.|||Embryonic lethality due to a developmental arrest during the establishment of the blastocyst.|||Expressed in early embryos at the 4-cell, blastocyst (3.5 dpc) and epiblast (7 dpc) stages (PubMed:12620990, PubMed:21425410). Expression is restricted to the interior part of the morula and the inner cell mass (ICM) of the blastocyst (PubMed:21425410). Detected in primordial germ cells (at 10 dpc) and undifferentiated embryonic stem cells (PubMed:12620990, PubMed:21425410).|||Interacts with UHRF1.|||Promotes maintenance and self-renewal of pluripotent embryonic stem cells (ESCs), downstream of LIF/STAT3 (PubMed:21425410). Maintains the pluripotency state of ESCs by repressing DNA methylation through the regulation of UHRF1 stability. Mediates the proteasomal degradation of UHRF1. Is required for the establishment of the blastocyst (PubMed:28604677).|||Seems to be specific to pluripotent tissues in the early embryo. Not detected in somatic tissues.|||Sequence of unknown origin in the N-terminal part. http://togogenome.org/gene/10090:Kif4 ^@ http://purl.uniprot.org/uniprot/P33174 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Chromokinesin subfamily.|||Binds 1 [4Fe-4S] cluster (By similarity). In the presence of oxygen, the [4Fe-4S] cluster may be converted to [2Fe-2S] (By similarity).|||Chromosome|||Expressed in pyramidal cells in juvenile hippocampus, granular cells in juvenile cerebellar cortex and in adult spleen.|||Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (By similarity). Required for mitotic chromosomal positioning and bipolar spindle stabilization.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Tfb2m ^@ http://purl.uniprot.org/uniprot/B2RSE6|||http://purl.uniprot.org/uniprot/Q3TL26 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family. KsgA subfamily.|||Homodimer. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Interacts with mitochondrial RNA polymerase POLRMT. Interacts with TFAM.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mitochondrion|||S-adenosyl-L-methionine-dependent rRNA methyltransferase which may methylate two specific adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 12S mitochondrial rRNA (By similarity). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (PubMed:15526033). In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:15526033). Stimulates transcription independently of the methyltransferase activity (By similarity).|||Ubiquitously expressed. http://togogenome.org/gene/10090:Wwc2 ^@ http://purl.uniprot.org/uniprot/Q6NXJ0 ^@ Similarity ^@ Belongs to the WWC family. http://togogenome.org/gene/10090:Rsph4a ^@ http://purl.uniprot.org/uniprot/Q8BYM7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flagellar radial spoke RSP4/6 family.|||Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB (PubMed:34871179). Interacts with RSPH1 (PubMed:34871179). Interacts with RSPH3B (PubMed:34871179). Interacts with RSPH6A (PubMed:30185526). Interacts with RSPH9 (PubMed:34871179).|||Expressed in the trachea, ependymal cells and oviduct (at protein level) (PubMed:32203505, PubMed:30239614, PubMed:34871179). Abesent from sperm (at protein level) (PubMed:34871179). Expressed in brain, kidney and testis.|||Functions as part of axonemal radial spoke complexes that play an important role in ciliary motility (PubMed:32203505, PubMed:34871179). Essential for triplet radial spokes (RS1, RS2 and RS3) head assembly in the motile cilia (PubMed:32203505).|||Mice show hydrocephalus and the tracheal and ependymal cell cilia show clockwise rotation motion instead of planar beating (PubMed:32203505). All three types of radial spoke heads (RS1, RS2 and RS3) are missing in the tracheal cilia (PubMed:32203505).|||cilium axoneme http://togogenome.org/gene/10090:Sp6 ^@ http://purl.uniprot.org/uniprot/Q9ESX2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Develops fewer, smaller, incisors at 3 months of age in a transcription factor ASCL5/AmeloD knockout background (PubMed:30426815). Epithelial cell invasion is inhibited and CDH1/E-cadherin ectopically expressed in dental epithelial cells at 3 months of age, in an ASCL5 knockout background (PubMed:30426815).|||Nucleus|||Promotes cell proliferation (PubMed:14551215). Plays a role in tooth germ growth (PubMed:30426815). Plays a role in the control of enamel mineralization. Binds the AMBN promoter (By similarity).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Ubiquitous. Preferentially expressed by proliferating epithelial cells of teeth, hair follicles and limbs. http://togogenome.org/gene/10090:Septin9 ^@ http://purl.uniprot.org/uniprot/A2A6U3|||http://purl.uniprot.org/uniprot/Q80UG5 ^@ Developmental Stage|||Disease Annotation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8 dpc mainly expressed in the lateral plate mesoderm and the somites. Beginning at 9 dpc the lateral plate expression is clearly focused in the developing fore- and hindlimb buds. In the cephalic region, expressed in the first and second branchial arch, in the nasal process and around the otic pit. At 9.5 dpc strongest expression is observed in the mesenchyme of the branchial arches, the limbs, and the developing dorsal root ganglia. Weak to intermediate expression is found in the neural epithelium. Expression is seen in the newly formed somites in the tail bud of older embryos. During formation of the digits, expression seems to outline the surviving tissue bordering it towards the apoptotic webbing. Expression is seen in the developing outer ear and in several areas known to be regulated by intensive epithelial mesenchymal interactions, like the viscera follicles and the developing mammary glands.|||Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Expressed in all tissues examined except muscle. Isoforms are differentially expressed in testes, kidney, liver, heart, spleen and brain.|||Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential).|||Putative proto-oncogene involved in T-cell lymphomagenesis. May play a role in leukemogenesis.|||Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments, and microtubules. GTPase activity is required for filament formation. Interacts with SEPTIN2, SEPTIN6, SEPTIN7, SEPTIN11 and SEPTIN14. Interacts with RTKN and ARHGEF18 (By similarity).|||Targeted by proviral insertion in T-cell lymphomas induced by the murine retrovirus SL3-3 MuLV.|||cytoskeleton http://togogenome.org/gene/10090:Jph3 ^@ http://purl.uniprot.org/uniprot/Q9ET77 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the junctophilin family.|||Cell membrane|||Endoplasmic reticulum membrane|||Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH3 is brain-specific and appears to have an active role in certain neurons involved in motor coordination and memory.|||Mice are viable and fertile, but have defects in balance/motor coordination tasks. Jph3 and Jph4 double knockout mice exhibit atypical depolarizing responses, irregular cerebellar plasticity due to abolished crosstalk in Purkinje cells. There is hyperphosphorylation of PRKCG and mild impairment of synaptic maturation. Exploratory activity, hippocampal plasticity and memory are impaired and there is abnormal foot-clasping reflex.|||Specifically expressed in brain. Highest levels in the olfactory tubercle, caudate putamen, nucleus accumbens, hippocampal formation, piriform cortex and cerebellar cortex. Expressed in disctete neurons sites. In hippocampal formation, expressed in dendrites of hippocampal pyramidal and denate granule cells. In cerebellum, it is highly expressed in Purkinge cells, while it is weakly expressed in granular cells.|||The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids. http://togogenome.org/gene/10090:Get4 ^@ http://purl.uniprot.org/uniprot/Q9D1H7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome.|||Belongs to the GET4 family.|||Component of the BAG6/BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with BAG6; the interaction is direct and localizes BAG6 in the cytosol.|||Ubiquitinated by RNF12, leading to proteasomal degradation. When unassembled from BAG6; ubiquitinylation is modulated by BAG6 quality control role and effectuated by RNF126.|||cytosol http://togogenome.org/gene/10090:Mtr ^@ http://purl.uniprot.org/uniprot/A6H5Y3 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the vitamin-B12 dependent methionine synthase family.|||Binds 1 zinc ion per subunit.|||Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol. MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine.|||Cytoplasm|||Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin (By similarity).|||Monomer. Dimer. Forms a multiprotein complex with MMACHC, MMADHC and MTRR. http://togogenome.org/gene/10090:Tfdp1 ^@ http://purl.uniprot.org/uniprot/Q08639|||http://purl.uniprot.org/uniprot/Q3V3X3|||http://purl.uniprot.org/uniprot/Q9CYZ7|||http://purl.uniprot.org/uniprot/Q9D297 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E2F/DP family.|||Can stimulate E2F-dependent transcription. Binds DNA cooperatively with E2F family members through the E2 recognition site, 5'-TTTC[CG]CGC-3', found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The E2F1:DP complex appears to mediate both cell proliferation and apoptosis. Blocks adipocyte differentiation by repressing CEBPA binding to its target gene promoters (PubMed:20176812).|||Component of the E2F:DP transcription factor complex. Forms heterodimers with E2F family members. The complex can interact with hypophosphorylated retinoblastoma protein RB1 and related proteins (RBL1 and RBL2) that inhibit the E2F transactivation domain. This repression involves recruitment of histone deacetylase (HDAC). During the cell cycle, from mid-to-late G1 phase, RB family members become phosphorylated, detach from the DRTF1/E2F complex to render E2F transcriptionally active. Part of the E2F6.com-1 complex in G0 phase is composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 YAF2. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. The complex TFDP1:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target gene promoters and represses its transcriptional activity (By similarity).|||Cytoplasm|||In the intestinal epithelium, first expressed in undifferentiated and mesenchymal tissues, levels increasing by 12.5 dpc in the epithelial compartment. With epithelial differentiation at 15.5 dpc, Its expression increases substantially in the intervillus epithelium with lower levels in the mesenchyme. At later stages, expression continues in the intervillus epithelium. Also found at lower levels in the developing villi. In the developing brain, highest levels found between 11.5 and 13.5 dpc in the ventricular region. In the developing retina, it is expressed both in retinoblast and ganglion cell layers from 14.5 dpc to 6 days after birth. In other developing tissues, its expression is highest in the thymus. Also present in kidney, lung, liver, heart and chondrocytes. Weakly expressed in skeletal muscle and absent from choroid plexus.|||Nucleus|||Phosphorylation by E2F1-bound cyclin A-CDK2, in the S phase, inhibits E2F-mediated DNA binding and transactivation.|||Ubiquitinated by the BCR(KBTBD5) complex, leading to its subsequent degradation. http://togogenome.org/gene/10090:Nipsnap3b ^@ http://purl.uniprot.org/uniprot/B1AWZ5|||http://purl.uniprot.org/uniprot/Q9CQE1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NipSnap family.|||cytosol http://togogenome.org/gene/10090:Xpnpep3 ^@ http://purl.uniprot.org/uniprot/B7ZMP1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M24B family.|||Binds 2 manganese ions per subunit.|||Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala. Also shows low activity towards peptides with Ala or Ser at the P1 position. Promotes TNFRSF1B-mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling.|||Cytoplasm|||Expressed in brain, kidney, heart, liver, skeletal muscle and testis.|||Homodimer. Interacts with TNFRSF1B/TNFR2 (activated) and TRAF2.|||Mitochondrion http://togogenome.org/gene/10090:Rab25 ^@ http://purl.uniprot.org/uniprot/Q9WTL2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasmic vesicle|||Interacts with RAB11FIP1, RAB11FIP2, RAB11FIP3 and RAB11FIP4. Interacts (via the hypervariable C-terminal region) with ITGB1 (via the cytoplasmic region); the interaction is GTP-dependent. Interacts with ITGAV. Associates with the integrin alpha-V/beta-1 heterodimer. Interacts with VPS33B (By similarity).|||Involved in the regulation of cell survival. Promotes invasive migration of cells in which it functions to localize and maintain integrin alpha-V/beta-1 at the tips of extending pseudopodia. Involved in the regulation of epithelial morphogenesis through the control of CLDN4 expression and localization at tight junctions (PubMed:22696678). May selectively regulate the apical recycling pathway. Together with MYO5B regulates transcytosis (By similarity).|||pseudopodium membrane http://togogenome.org/gene/10090:Rbm41 ^@ http://purl.uniprot.org/uniprot/Q8JZV4 ^@ Function ^@ May bind RNA. http://togogenome.org/gene/10090:Erich3 ^@ http://purl.uniprot.org/uniprot/F6QRE9 ^@ Function|||Subcellular Location Annotation ^@ Component of the primary cilium that controls cilium formation and length. May function within retrograde intraflagellar transport (IFT)-associated pathways to remove signaling proteins from primary cilia. Also involved in neuronal vesicle biogenesis and neurotransmitter vesicular function.|||Cytoplasm|||cilium http://togogenome.org/gene/10090:Krt83 ^@ http://purl.uniprot.org/uniprot/E9Q1Y9 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Dnai4 ^@ http://purl.uniprot.org/uniprot/E9PYY5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Dynein axonemal particle|||Highly expressed in tissues containing motile cilia, including the trachea, lung, oviduct, and testis.|||Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains. Associated with axonemal dynein subunits such as, DNAH2, DNAI3, and DYNLT1 (PubMed:30060180). Interacts with DYNLT1 (PubMed:30060180).|||Plays a critical role in the assembly of axonemal dynein complex, thereby playing a role in ciliary motility.|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Prg3 ^@ http://purl.uniprot.org/uniprot/Q9JL95 ^@ Function|||Tissue Specificity ^@ Expressed in bone marrow, spleen, and thymus. Not detected in heart, liver or lung.|||Possesses similar cytotoxic and cytostimulatory activities to PRG2/MBP. http://togogenome.org/gene/10090:Homez ^@ http://purl.uniprot.org/uniprot/A0A0R4J108|||http://purl.uniprot.org/uniprot/Q80W88 ^@ Caution|||Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ First expressed at 7 dpc. At 8.5-9 dpc expressed in all developing organs. Later on during embryogenesis shows a more restricted expression pattern. At 9.5-12.5 dpc it is strongly expressed in the developing brain, optic vesicle and the otic placode.|||Homodimer or heterodimer (Potential). Interacts with HOXC8 (By similarity).|||It is uncertain whether Met-1 or Met-25 is the initiator.|||May function as a transcriptional regulator.|||May result from the retention of an intron.|||Nucleus|||Ubiquitous. Strongly expressed in testis. http://togogenome.org/gene/10090:Wdr76 ^@ http://purl.uniprot.org/uniprot/A6PWY4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the WD repeat DDB2/WDR76 family.|||Interacts with CUL4A and/or CUL4B.|||Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC. http://togogenome.org/gene/10090:Crip2 ^@ http://purl.uniprot.org/uniprot/Q9DCT8 ^@ Developmental Stage|||Subunit ^@ In the embryo, its expression is primarily restricted to the developing heart. In situ hybridization showed expression at 7.75 dpc in the paired heart-forming primordia prior to linear heart-tube formation. At 8.5 dpc, strong expression is detected in the heart, with equal expression in both heart chambers. Expression is detected in both myocardium and endocardium, and in vascular endothelium. Later in fetal development low levels of expression is detected outside the heart, including dorsal root ganglia and the spinal cord. In the adult, it is expressed at highest levels in the heart, and at lower levels in the brain, skeletal muscle and aorta.|||Interacts with TGFB1I1. http://togogenome.org/gene/10090:Acad11 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0I6|||http://purl.uniprot.org/uniprot/Q80XL6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acyl-CoA dehydrogenase, that exhibits maximal activity towards saturated C22-CoA. Probably participates in beta-oxydation and energy production but could also play a role in the metabolism of specific fatty acids to control fatty acids composition of cellular lipids in brain.|||Belongs to the acyl-CoA dehydrogenase family.|||Homodimer.|||Mitochondrion membrane|||Peroxisome http://togogenome.org/gene/10090:Gm12250 ^@ http://purl.uniprot.org/uniprot/Q0GUM3 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||By IFNG/IFN-gamma (PubMed:16959883). Induced by IRF1 in response to bacterial infection (PubMed:27693356).|||Cytoplasmic vesicle membrane|||Homooligomer; homooligomerization occurs upon GTP-binding and is required for the association with membranous structures (PubMed:23785284, PubMed:27693356). Homodimer; GDP-binding induces formation of an inactive head-to-head homodimer (PubMed:33469160).|||Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens by mediating cytosolic release of pathogenic ligands that activate the inflammasomes (PubMed:16959883, PubMed:20109161, PubMed:27693356, PubMed:30062052, PubMed:30510167, PubMed:34694641). Following infection, recruited to the membrane of pathogens in a GBP-dependent manner and mediates disruption of the pathogen membrane, liberating ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (PubMed:27693356, PubMed:30062052, PubMed:30510167). Promotes AIM2 and NLRP3 inflammasome activation following A.fumigatus infection by liberating beta-glucan, which directly triggers inflammasome assembly (PubMed:30510167). Promotes NLRP3 inflammasome activation following influenza A virus infection (PubMed:34694641).|||Membrane|||Myristoylation is required for localization to pathogen-containing vacuoles (PubMed:23785284). http://togogenome.org/gene/10090:Npat ^@ http://purl.uniprot.org/uniprot/Q8BMA5 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NPAT family.|||Expression peaks at the G1/S phase boundary.|||Interacts with the cylin/CDK complexes CCNE1/CDK2 and CCNA1/CDK2. Interacts with BZW1, CASP8AP2, CREBBP, MIZF and YY1. Interacts with the RUVBL1, RUVBL2 and TRRAP subunits of the NuA4 complex. May also interact with GAPDH, NME1, NME2 and STIP1 (By similarity).|||Nucleus|||Phosphorylated at Ser-771, Ser-773, Ser-1096, Thr-1264 and Thr-1343 by CCNE1/CDK2 at G1-S transition and until prophase, which promotes association with histone gene clusters and stimulates activation of histone transcription. Also phosphorylated by CCNA1/CDK2 in vitro (By similarity).|||Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters (By similarity). Required for early embryonic development.|||The LisH domain is required for the activation of histone gene transcription. http://togogenome.org/gene/10090:Khdrbs1 ^@ http://purl.uniprot.org/uniprot/Q60749 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated. Positively correlates with ability to bind RNA (By similarity).|||Arginine methylation is required for nuclear localization. Inhibits interaction with Src-like SH3 domains, but not interaction with WW domains of WBP4/FBP21 and FNBP4/FBP30 (By similarity).|||Belongs to the KHDRBS family.|||Cytoplasm|||In adult cerebellum expressed in most neuronal cell populations, specifically in cerebellar granule cells of the internal granular layer, ROR(alpha)-positive Purkinje cells, internal granular layer and molecular layer interneurons (at protein level).|||In the developing cerebellum expression is high at birth and declines over the first 3 weeks. At P7 highly expressed in granule cell precursor cells in the external granular layer and mature granule cells of the internal granule layer.|||Membrane|||Nucleus|||Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Positively regulates the association of constitutive transport element (CTE)-containing mRNA with large polyribosomes and translation initiation. May not be involved in the nucleocytoplasmic export of unspliced (CTE)-containing RNA species. RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds to RNA containing 5'-[AU]UAA-3' as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). In cooperation with HNRNPA1 modulates alternative splicing of BCL2L1 by promoting splicing toward isoform Bcl-X(S), and of SMN1 (By similarity). Can regulate CD44 alternative splicing in a Ras pathway-dependent manner. Can regulate alternative splicing of NRXN1 and NRXN3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. In a neuronal activity-dependent manner cooperates synergistically with KHDRBS2/SLIM-1 in regulation of NRXN1 exon skipping at AS4. The cooperation with KHDRBS2/SLIM-1 is antagonistic for regulation of NXRN3 alternative splicing at AS4 (PubMed:12478298, PubMed:22196734, PubMed:24469635).|||Self-associates to form homooligomers when bound to RNA, oligomerization appears to be limited when binding to proteins (PubMed:9315629). Interacts with KHDRBS3/SLIM-2 and KHDRBS2/SLIM-1; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:10077576, PubMed:24469635). Interacts with RASA1, FYN, GRB2, PLCG1, SRC, RBMY1A1, CBP, PRMT1 (PubMed:7799925, PubMed:7512695, PubMed:10077576, PubMed:10823932, PubMed:12496368, PubMed:12529443). Interacts with PTK6 (via SH3 and SH2 domains). Forms a complex with ILF2, ILF3, YLPM1, RBMX, NCOA5 and PPP1CA. Binds WBP4/FBP21 (via WW domains), FNBP4/FBP30 (via WW domains). Interacts (via Arg/Gly-rich-flanked Pro-rich regions) with FYN (via the SH3 domain). Interacts with APC, HNRNPA1 (By similarity). Interacts with the non-receptor tyrosine kinase SRMS; the interaction leads to phosphorylation of KHDRBS1 (By similarity). Interacts with ZBTB7A; negatively regulates KHDRBS1 splicing activity toward BCL2L1 (By similarity).|||The KH domain is required for binding to RNA.|||The Pro-rich domains are flanked by Arg/Gly-rich motifs which can be asymmetric dimethylated on arginine residues to give the DMA/Gly-rich regions. Selective methylation on these motifs can modulate protein-protein interactions (By similarity).|||Tyrosine phosphorylated by several non-receptor tyrosine kinases including LCK, FYN and JAK3. Also tyrosine phosphorylated by the non-receptor tyrosine kinase SRMS in an EGF-dependent manner (By similarity). Phosphorylation by PTK6 negatively regulates its RNA binding ability. Phosphorylation by PTK6 at Tyr-440 dictates the nuclear localization of KHDRBS1. Phosphorylation by MAPK1 at Ser-58, Thr-71 and Thr-84 regulates CD44 alternative splicing by promoting CD44 exon v5 inclusion. http://togogenome.org/gene/10090:Prdm16 ^@ http://purl.uniprot.org/uniprot/A2A931|||http://purl.uniprot.org/uniprot/A2A933|||http://purl.uniprot.org/uniprot/A2A934|||http://purl.uniprot.org/uniprot/A2A935|||http://purl.uniprot.org/uniprot/Q8BNF5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRDM16 family.|||Binds DNA and functions as a transcriptional regulator (PubMed:18483224). Displays histone methyltransferase activity and monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (PubMed:22939622). Probably catalyzes the monomethylation of free histone H3 in the cytoplasm which is then transported to the nucleus and incorporated into nucleosomes where SUV39H methyltransferases use it as a substrate to catalyze histone H3 'Lys-9' trimethylation (PubMed:22939622). Likely to be one of the primary histone methyltransferases along with MECOM/PRDM3 that direct cytoplasmic H3K9me1 methylation (PubMed:22939622). Functions in the differentiation of brown adipose tissue (BAT) which is specialized in dissipating chemical energy in the form of heat in response to cold or excess feeding while white adipose tissue (WAT) is specialized in the storage of excess energy and the control of systemic metabolism (PubMed:17618855, PubMed:18483224). Together with CEBPB, regulates the differentiation of myoblastic precursors into brown adipose cells (PubMed:18719582, PubMed:19641492). Functions as a repressor of TGF-beta signaling.|||Cytoplasm|||Enriched in BAT compared to WAT. Detected in heart, lung, kidney and brain. Expressed in nuclei of cardiomyocytes.|||Expressed at 12.5 dpc, 13.5 dpc and 14.5 dpc. Expressed in orofacial tissues, heart, liver, brain and limb bud. At 13.5 dpc, expressed throughout the ventricular myocardium, including endocardium and epicardium.|||Interacts with CEBPA, CEBPB and CEBPD; the interaction is direct (PubMed:19641492). Interacts with PPARG and PPARA; controls brown adipocytes (PubMed:18719582). Interacts with CTBP1 and CTBP2; represses the expression of WAT-specific genes (PubMed:18483224). Interacts with PPARGC1A and PPARGC1B; interaction with PPARGC1A or PPARGC1B activates the transcription of BAT-specific gene (PubMed:18483224, PubMed:17618855). Interacts with HDAC1, SKI and SMAD2; the interaction with SKI promotes the recruitment of SMAD3-HDAC1 complex on the promoter of TGF-beta target genes (Probable). Interacts with ZNF516; the interaction is direct and may play a role in the transcription of brown adipose tissue-specific gene (PubMed:25578880).|||Mice die at birth but embryos display altered brown adipose tissue differentiation.|||Nucleus http://togogenome.org/gene/10090:Scgb2b20 ^@ http://purl.uniprot.org/uniprot/J3QK77 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Tapbp ^@ http://purl.uniprot.org/uniprot/Q9R233 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with TAP1 and is thus a subunit of the TAP complex. Interaction with TAP1 is TAP2 independent and is required for efficient peptide-TAP interaction. Obligatory mediator for the interaction between newly assembled MHC class I molecules, calreticulin, ERp57 and TAP. Up to 4 MHC class I/tapasin complexes bind to 1 TAP.|||Involved in the association of MHC class I with transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading).|||The N-terminus is required for efficient association with MHC class I molecule and for a stable interaction between MHC I and calreticulin. Binding to TAP is mediated by the C-terminal region (By similarity). http://togogenome.org/gene/10090:Fam133b ^@ http://purl.uniprot.org/uniprot/Q9CVI2 ^@ Miscellaneous|||Similarity ^@ Belongs to the FAM133 family.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Tprgl ^@ http://purl.uniprot.org/uniprot/Q9DBS2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TPRG1 family.|||Forms homomultimers (By similarity). Multimerization appears to be important for presynaptic targeting (By similarity). Interacts with BSN (PubMed:17869247).|||Phosphorylated. Phosphorylation promotes association with synaptic vesicle membranes.|||Presynaptic active zone|||Presynaptic protein involved in the synaptic transmission tuning. Regulates synaptic release probability by decreasing the calcium sensitivity of release.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Sval1 ^@ http://purl.uniprot.org/uniprot/Q9D2X6 ^@ Similarity|||Subunit ^@ Belongs to the PIP family.|||Monomer. Interacts with AZGP1. http://togogenome.org/gene/10090:Myot ^@ http://purl.uniprot.org/uniprot/Q9JIF9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the myotilin/palladin family.|||Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells (By similarity).|||Expressed in skeletal muscle (at protein level).|||Homodimer. Interacts with ACTA1, ACTN1, FLNA, FLNB, FLNC, and MYOZ2. Interacts with the C-terminal region of MYOZ1 (By similarity).|||No visible phenotype. Mutant mice develop normally, have a normal life span, and their muscle capacity does not significantly differ from wild-type animals, even after prolonged physical stress.|||Z line|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Efl1 ^@ http://purl.uniprot.org/uniprot/Q8C0D5 ^@ Function|||Similarity|||Subunit ^@ Associates with the 60S ribosomal subunit. Found in a complex consisting of the 60S ribosomal subunit, SBDS and EFL1.|||Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family.|||Involved in the biogenesis of the 60S ribosomal subunit and translational activation of ribosomes. Together with SBDS, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Has low intrinsic GTPase activity. GTPase activity is increased by contact with 60S ribosome subunits (By similarity). http://togogenome.org/gene/10090:Or14a257 ^@ http://purl.uniprot.org/uniprot/Q7TS06 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:C1qtnf6 ^@ http://purl.uniprot.org/uniprot/Q6IR41 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Snx8 ^@ http://purl.uniprot.org/uniprot/Q8CFD4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||Early endosome membrane|||May be involved in several stages of intracellular trafficking. May play a role in intracellular protein transport from early endosomes to the trans-Golgi network (By similarity). http://togogenome.org/gene/10090:Uncx ^@ http://purl.uniprot.org/uniprot/O08934 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Unc-4 subfamily.|||Expressed in the paraxial mesoderm, in the developing kidney and central nervous system. In the somite, it is restricted to the caudal half of the newly formed somite and sclerotome. In the central nervous system, it is detected in the developing spinal cord, hindbrain, mesencephalon and telencephalon. Expressed in adult and embryonic magnocellular neurons of the hypothalamo-neurohypophysial system.|||Marker of antero-posterior subdivisions of the somite.|||Mice die perinatally and exhibit severe malformations of the axial skeleton. Pedicles of the neural arches and proximal ribs are not formed. In addition, dorsal root ganglia are disorganized. In the hypothalamo-neurohypophysial system, neurons are viable and able to express neuropeptides; however, the connectivity of magnocellular neurons with posterior pituitary elements is compromised.|||Nucleus|||Transcription factor involved in somitogenesis and neurogenesis. Required for the maintenance and differentiation of particular elements of the axial skeleton. May act upstream of PAX9. Plays a role in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and to deliver hormones for control of peripheral functions. http://togogenome.org/gene/10090:Pmpcb ^@ http://purl.uniprot.org/uniprot/Q9CXT8 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M16 family.|||Binding to PMPCA is required for catalytic activity.|||Binds 1 zinc ion per subunit.|||Catalytic subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins (By similarity). Preferentially, cleaves after an arginine at position P2 (By similarity). Required for PINK1 turnover by coupling PINK1 mitochondrial import and cleavage, which results in subsequent PINK1 proteolysis (By similarity).|||Heterodimer of PMPCA (alpha) and PMPCB (beta) subunits, forming the mitochondrial processing protease (MPP) in which PMPCA is involved in substrate recognition and binding and PMPCB is the catalytic subunit.|||Mitochondrion matrix http://togogenome.org/gene/10090:Fh1 ^@ http://purl.uniprot.org/uniprot/P97807 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II fumarase/aspartase family. Fumarase subfamily.|||Catalyzes the dehydration of L-malate to fumarate (PubMed:23643539). Fumarate metabolism in the cytosol plays a role during urea cycle and arginine metabolism; fumarate being a by-product of the urea cycle and amino-acid catabolism (PubMed:23643539). Also plays a role in DNA repair by promoting non-homologous end-joining (NHEJ) (By similarity). In response to DNA damage and phosphorylation by PRKDC, translocates to the nucleus and accumulates at DNA double-strand breaks (DSBs): acts by catalyzing formation of fumarate, an inhibitor of KDM2B histone demethylase activity, resulting in enhanced dimethylation of histone H3 'Lys-36' (H3K36me2) (By similarity).|||Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.|||Catalyzes the reversible stereospecific interconversion of fumarate to L-malate (PubMed:23643539). Experiments in different species have demonstrated that specific isoforms of this protein act in defined pathways and favor one direction over the other (Probable).|||Chromosome|||Embryonic lethality (PubMed:17418408). Conditional deletion in the kidney leads to the development of renal cysts, reminiscent of hereditary leiomyomatosis and renal cell cancer (HLRCC) phenotype in human (PubMed:17418408). Renal cysts are caused by accumulation of fumarate that promotes the formation of non-enzymatic post-translational modification cysteine S-succination (S-(2-succinyl)cysteine) on proteins, such as Keap1 (PubMed:22014577).|||Homotetramer. Interacts with H2AZ1.|||Mitochondrion|||Nucleus|||Phosphorylation at Thr-233 by PRKDC in response to DNA damage promotes translocation to the nucleus and recruitment to DNA double-strand breaks (DSBs).|||There are 2 substrate-binding sites: the catalytic A site, and the non-catalytic B site that may play a role in the transfer of substrate or product between the active site and the solvent. Alternatively, the B site may bind allosteric effectors.|||cytosol http://togogenome.org/gene/10090:Scpep1 ^@ http://purl.uniprot.org/uniprot/Q920A5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S10 family.|||May be involved in vascular wall and kidney homeostasis.|||Secreted http://togogenome.org/gene/10090:Naaa ^@ http://purl.uniprot.org/uniprot/G3XA18|||http://purl.uniprot.org/uniprot/Q3V023|||http://purl.uniprot.org/uniprot/Q9D7V9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoproteolytic cleavage at pH 4.5 gives rise to the alpha and beta subunit (PubMed:30301806). Cleavage gives rise to a conformation change that activates the enzyme. The same catalytic Cys residue mediates the autoproteolytic cleavage and subsequent hydrolysis of lipid substrates (By similarity).|||Belongs to the acid ceramidase family.|||Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-stearoylethanolamine > N-oleoylethanolamine > N-linoleoylethanolamine > N-arachidonoylethanolamine.|||Heterodimer of an alpha and a beta subunit, produced by autocatalytic cleavage.|||Heterodimer.|||Intron retention.|||Lysosome|||Membrane|||N-glycosylated (PubMed:30301806). Tunicamycin treatment causes a reduction in specific activity against N-palmitoylethanolamine (By similarity). http://togogenome.org/gene/10090:Rfx8 ^@ http://purl.uniprot.org/uniprot/D3YU81 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RFX family.|||May be a transcription factor.|||Nucleus http://togogenome.org/gene/10090:Derl1 ^@ http://purl.uniprot.org/uniprot/Q99J56 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the derlin family.|||Endoplasmic reticulum membrane|||Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. Forms homotetramers which encircle a large channel traversing the endoplasmic reticulum (ER) membrane. This allows the retrotranslocation of misfolded proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome. The channel has a lateral gate within the membrane which provides direct access to membrane proteins with no need to reenter the ER lumen first. May mediate the interaction between VCP and the misfolded protein. Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway.|||Homotetramer (By similarity). The four subunits of the tetramer are arranged in a twofold symmetry (By similarity). Forms homo- and heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than that between DERL2 and DERL3. Interacts (via SHP-box motif) with VCP (By similarity). Interacts with AMFR, SELENOS, SEL1L, SELENOK and SYVN1, as well as with SEL1L-SYVN1 and VCP-SELENOS protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with NGLY1 and YOD1. Does not bind to EDEM1 (By similarity). Interacts with DNAJB9 (PubMed:22267725). Interacts with RNF103. Interacts with HM13. Interacts with XBP1 isoform 1 (via luminal/ectodomain domain); the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage. Interacts with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control. May interact with UBXN6 (By similarity). Interacts with ZFAND2B; probably through VCP (PubMed:24160817). Interacts with CCDC47 (PubMed:25009997). Interacts with C18orf32 (By similarity). May interact with TRAM1 (By similarity).|||Up-regulated in response to endoplasmic reticulum stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR).|||Widely expressed, with lowest levels in brain and heart. http://togogenome.org/gene/10090:Semp2l2b ^@ http://purl.uniprot.org/uniprot/D3Z741 ^@ Similarity ^@ Belongs to the peptidase C48 family. http://togogenome.org/gene/10090:Hspa12b ^@ http://purl.uniprot.org/uniprot/Q9CZJ2 ^@ Similarity|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||Expressed most strongly in heart with little or no expression in other tissues. In the aorta, preferentially expressed in lesions. http://togogenome.org/gene/10090:Serpina3k ^@ http://purl.uniprot.org/uniprot/A0A0R4J0I1|||http://purl.uniprot.org/uniprot/P07759 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Contrapsin inhibits trypsin-like proteases.|||Expressed in liver and secreted in plasma.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Tekt4 ^@ http://purl.uniprot.org/uniprot/Q149S1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tektin family.|||Detected in testis from postnatal day 16 onwards, reaching maximal levels by postnatal day 18.|||Detected in testis, where it is weakly expressed in round spermatids, and strongly expressed in the flagellum of step 16 elongated spermatids (at protein level) (PubMed:17244819). Expressed in spermatozoa (PubMed:36708031). In the sperm flagellum, localizes to the principal piece and midpiece (at protein level) (PubMed:17244819, PubMed:16596631). Specifically expressed in testis; not detected in other tissues tested (PubMed:17244819).|||In a 129S5/SvEvBrd genetic background, males show progressive reduction in fertility with almost complete loss of fertility after 5 months of breeding. Testis weight and histology appear normal. Spermatozoa have significantly reduced forward motility. The sperm flagellum shows defective bending in the midpiece region which impairs waveform propagation and forward propulsion. Sperm ATP levels deplete significantly over time, probably as a result of excess energy consumption from inefficient flagellar beating. The ultrastructure of the flagellum has some subtle abnormalities with an enlarged space between the mitochondrial sheath and the outer dense fibers. In a mixed C57BL/6J;129S5/SvEvBrd genetic background, male fertility is not significantly affected.|||Interacts with TEKT3.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules (By similarity). Contributes to normal sperm motility (PubMed:17244819).|||cilium axoneme|||flagellum http://togogenome.org/gene/10090:Slc17a6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0A6|||http://purl.uniprot.org/uniprot/Q8BLE7 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.|||Cell membrane|||Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-). The allosteric requirement for H(+) efficiently prevents non-vesicular efflux across the plasma membrane (By similarity). The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration (PubMed:11432869).|||Expressed in brain throughout development. Transiently expressed in hippocampal neurons during the first week after birth, with expression decreasing thereafter.|||Expressed in brain. Expressed in hippocampal neurons (at protein level).|||Membrane|||Mice exhibit an elevated rate of perinatal lethality (PubMed:17108179). Surviving animals display a strong reduction in evoked glutamergic responses in thalamic neurons (PubMed:17108179). Reduction of protein level in homozygous and heterozygous knockouts leads to a graded reduction in the amplitude of the postsynaptic response to single vesicle fusion in thalamic neurons, consistent with a role for this protein in determining quantal size (PubMed:17108179). Decrease in the number of retinal hyaloid vessels at postnatal day 8 as a result of precocious regression (PubMed:30936473).|||Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, proton, potassium, sodium and phosphate (PubMed:17108179, PubMed:33440152, PubMed:25433636, PubMed:11432869). At the synaptic vesicle membrane, mainly functions as a uniporter which transports preferentially L-glutamate but also, phosphate from the cytoplasm into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells (PubMed:17108179, PubMed:11432869). The L-glutamate or phosphate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (PubMed:11432869). In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane therefore affects the proton electrochemical gradient and promotes synaptic vesicles acidification (By similarity). Moreover, functions as a vesicular K(+)/H(+) antiport allowing to maintain the electrical gradient and to decrease chemical gradient and therefore sustain vesicular glutamate uptake (PubMed:25433636). The vesicular H(+)/H(+) antiport activity is electroneutral (PubMed:25433636). At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation (PubMed:33440152). The symporter activity is driven by an inside negative membrane potential and is electrogenic (PubMed:33440152). Also involved in the regulation of retinal hyaloid vessel regression during postnatal development (PubMed:30936473). May also play a role in the endocrine glutamatergic system of other tissues such as pineal gland and pancreas (By similarity).|||The phosphorylation site Tyr-195 is located in a predicted transmembrane region.|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Mdc1 ^@ http://purl.uniprot.org/uniprot/E9QK89|||http://purl.uniprot.org/uniprot/Q5PSV9 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Homodimer. Interacts with several proteins involved in the DNA damage response, although not all these interactions may be direct. Interacts with CHEK2, which requires ATM-mediated phosphorylation within the FHA domain of CHEK2. Interacts constitutively with the BRCA1-BARD1 complex, SMC1A and TP53BP1. Interacts with ATM and FANCD2, and these interactions are reduced upon DNA damage. Also interacts with the PRKDC complex, composed of XRCC6/KU70, XRCC5/KU80 and PRKDC/XRCC7. This interaction may be required for PRKDC autophosphorylation, which is essential for DNA double strand break (DSB) repair. When phosphorylated by ATM, interacts with RNF8 (via FHA domain). Interacts with CEP164. When phosphorylated, interacts with APTX (via FHA-like domain) (By similarity). Interacts with H2AX, which requires phosphorylation of H2AX. Interacts with the MRN complex, composed of MRE11, RAD50, and NBN.|||Nucleus|||Phosphorylated upon exposure to ionizing radiation (IR), ultraviolet radiation (UV), and hydroxyurea (HU). Phosphorylation in response to IR requires ATM, NBN, and possibly CHEK2. Also phosphorylated during the G2/M phase of the cell cycle and during activation of the mitotic spindle checkpoint. Phosphorylation at Thr-4 by ATM stabilizes and enhances homodimerization via the FHA domain (By similarity).|||Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (By similarity).|||Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1.|||Sumoylation at Lys-1461 by PIAS4 following DNA damage promotes ubiquitin-mediated degradation.|||Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1, these repeats are required for localization to chromatin which flanks sites of DNA damage marked by 'Ser-139' phosphorylation of H2AX (By similarity).|||Ubiquitinated by RNF4, leading to proteasomal degradation; undergoes 'Lys-48'-linked polyubiquitination. http://togogenome.org/gene/10090:Vmn1r149 ^@ http://purl.uniprot.org/uniprot/E9PWL6 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Cables2 ^@ http://purl.uniprot.org/uniprot/Q8K3M5 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family.|||Binds to CDK3, CDK5 and ABL1. The C-terminal cyclin-box-like region binds to CDK5.|||Unknown. Probably involved in G1-S cell cycle transition.|||Widely expressed. http://togogenome.org/gene/10090:Oasl1 ^@ http://purl.uniprot.org/uniprot/Q8VI94 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2-5A synthase family.|||By type I interferon (IFN) and viruses.|||Cytoplasm|||Does not have 2'-5'-OAS activity, but can bind double-stranded RNA. Displays antiviral activity via an alternative antiviral pathway independent of RNase L.|||Specifically interacts with the ligand binding domain of the thyroid receptor (TR). TRIP14 does not require the presence of thyroid hormone for its interaction. Binds MBD1 (By similarity).|||nucleolus http://togogenome.org/gene/10090:Serpinb12 ^@ http://purl.uniprot.org/uniprot/Q9D7P9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Inhibits trypsin and plasmin, but not thrombin, coagulation factor Xa, or urokinase-type plasminogen activator. May play a role in cell differentiation.|||Interacts with SLFN12; as part of a pathway regulating cell differentiation. http://togogenome.org/gene/10090:Prr13 ^@ http://purl.uniprot.org/uniprot/Q9CQJ5 ^@ Function|||Subcellular Location Annotation ^@ Negatively regulates TSP1 expression at the level of transcription. This down-regulation was shown to reduce taxane-induced apoptosis (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or8s10 ^@ http://purl.uniprot.org/uniprot/A1L1B4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zc3hav1l ^@ http://purl.uniprot.org/uniprot/Q8BFR1 ^@ Caution ^@ Despite its name, it does not contain a canonical C3H1-type zinc-finger. http://togogenome.org/gene/10090:Srd5a1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J136|||http://purl.uniprot.org/uniprot/Q68FF9|||http://purl.uniprot.org/uniprot/Q8BUR8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the steroid 5-alpha reductase family.|||Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Parp1 ^@ http://purl.uniprot.org/uniprot/Q921K2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ARTD/PARP family.|||Chromosome|||Interacts (when auto-poly-ADP-ribosylated) with AIFM1.|||Nucleus|||Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.|||This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. http://togogenome.org/gene/10090:Zfp143 ^@ http://purl.uniprot.org/uniprot/O70230 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GLI C2H2-type zinc-finger protein family.|||Interacts with CHD8.|||Nucleus|||Transcriptional activator. Activates the gene for selenocysteine tRNA (tRNAsec). Binds to the SPH motif of small nuclear RNA (snRNA) gene promoters. Participates in efficient U6 RNA polymerase III transcription via its interaction with CHD8 (By similarity). http://togogenome.org/gene/10090:Panx1 ^@ http://purl.uniprot.org/uniprot/Q9JIP4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pannexin family.|||Cell membrane|||Endoplasmic reticulum membrane|||Homohexamer. Forms homomeric or PANX1/PANX2-heteromeric intercellular channels on coexpression in paired Xenopus oocytes.|||N-glycosylation may play a role in cell surface targeting (PubMed:17925379). Exists in three glycosylation states: non-glycosylated (GLY0), high-mannose glycosylated (GLY1), and fully mature glycosylated (GLY2) (By similarity).|||S-nitrosylation inhibits channel currents and ATP release.|||Structural component of the gap junctions and the hemichannels involved in the ATP release and nucleotide permeation. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis. Plays a critical role in oogenesis.|||Structural component of the gap junctions and the hemichannels. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis (By similarity).|||Widely expressed, including in cartilage, skin, spleen and brain.|||gap junction http://togogenome.org/gene/10090:Ccne1 ^@ http://purl.uniprot.org/uniprot/Q61457 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family. Cyclin E subfamily.|||Essential for the control of the cell cycle at the G1/S (start) transition.|||Found in adult spleen, and to a lesser extent in adult testis and brain.|||Interacts with CDK2 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts directly with UHRF2; the interaction ubiquitinates CCNE1 and appears to occur independently of CCNE1 phosphorylation (By similarity). Found in a complex with CDK2, CABLES1 and CCNA1 (PubMed:11585773). Interacts with INCA1 (By similarity).|||Nucleus|||Phosphorylation of both Thr-393 by GSK3 and Ser-397 by CDK2 creates a high affinity degron recognized by FBXW7, and accelerates degradation via the ubiquitin proteasome pathway. Phosphorylation at Thr-74 creates a low affinity degron also recognized by FBXW7 (By similarity).|||Ubiquitinated by UHRF2; appears to occur independently of phosphorylation. http://togogenome.org/gene/10090:D6Wsu163e ^@ http://purl.uniprot.org/uniprot/Q91YN0 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Plays a role in mast cell degranulation. http://togogenome.org/gene/10090:Rilpl1 ^@ http://purl.uniprot.org/uniprot/Q9JJC6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RILPL family.|||Interacts (when S-nitrosylated) with GAPDH (By similarity). Interacts with RAB8A; interaction is dependent on the phosphorylation of 'Thr-72' of RAB8A (PubMed:29125462). Interacts with RAB10 and RAB12; the interaction is dependent on the phosphorylation of 'Thr-73' of RAB10, and 'Ser-105' of RAB12 (By similarity).|||Neuroprotective protein, which acts by sequestring GAPDH in the cytosol and prevent the apoptotic function of GAPDH in the nucleus (By similarity). Competes with SIAH1 for binding GAPDH (By similarity). Does not regulate lysosomal morphology and distribution (By similarity). Plays a role in the regulation of cell shape and polarity (PubMed:23264467). Plays a role in cellular protein transport, including protein transport away from primary cilia (PubMed:23264467). Binds to RAB10 following LRRK2-mediated RAB10 phosphorylation which leads to inhibition of ciliogenesis (By similarity).|||S-nitrosylation is required for the interaction with GAPDH.|||centriole|||cilium|||cytosol http://togogenome.org/gene/10090:Trim21 ^@ http://purl.uniprot.org/uniprot/Q3U7K7|||http://purl.uniprot.org/uniprot/Q3UCL2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm http://togogenome.org/gene/10090:St6galnac6 ^@ http://purl.uniprot.org/uniprot/E9PUI0|||http://purl.uniprot.org/uniprot/Q9JM95|||http://purl.uniprot.org/uniprot/Z4YLR0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ After inflammation stimulus.|||Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||Membrane|||Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc onto glycolipids, forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer of a sialyl group onto the GalNAc or GlcNAc residue inside backbone core chains having a terminal sialic acid with an alpha-2,3-linkage on Gal. ST6GalNAcVI prefers glycolipids to glycoproteins, predominantly catalyzing the biosynthesis of ganglioside GD1alpha from GM1b. Also has activity toward GD1a and GT1b, and can generate DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside) (PubMed:10702226). Besides GMb1, MSGG and other glycolipids, it shows activity towards sialyl Lc4Cer generating disialyl Lc4Cer, which can lead to the synthesis of disialyl Lewis a (Le(a)), suggested to be a cancer-associated antigen (By similarity).|||Widely expressed, the gene expression is most abundant in colon, brain, liver, and heart. http://togogenome.org/gene/10090:Psors1c2 ^@ http://purl.uniprot.org/uniprot/Q80ZC9 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Armt1 ^@ http://purl.uniprot.org/uniprot/A6H630 ^@ Caution|||Domain|||Function|||PTM|||Similarity ^@ Automethylated.|||Belongs to the damage-control phosphatase family. Sugar phosphate phosphatase III subfamily.|||Human C6orf211 has been reportedly associated with a protein carboxyl methyltransferase activity, but whether this protein indeed has such an activity remains to be determined (By similarity). It has been later shown to belong to a family of metal-dependent phosphatases implicated in metabolite damage-control (By similarity).|||Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate (By similarity). Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism (By similarity). Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues (By similarity). Possibly methylates PCNA, suggesting it is involved in the DNA damage response (By similarity).|||Subfamily III proteins have a conserved RTxK motif about 40-50 residues from the C-terminus; the threonine may be replaced by serine or cysteine. http://togogenome.org/gene/10090:Ube2k ^@ http://purl.uniprot.org/uniprot/A0A0J9YU07|||http://purl.uniprot.org/uniprot/P61087|||http://purl.uniprot.org/uniprot/Q6ZWQ6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. Involved in stabilization of CASP12 during ER stress-mediated amyloid-beta neurotoxicity probably by inhibiting proteasome activity; in vitro ubiquitinates CASP12.|||Belongs to the ubiquitin-conjugating enzyme family.|||Cytoplasm|||Expressed at all stages of brain development and increases significantly between postnatal days 7 and 14.|||Expressed in the brain, with highest levels found in the mitral cells of the olfactory bulb, the pyramidal cell layer of the hippocampus and the Purkinje cells of the cerebellar cortex.|||Interacts with RNF138/NARF. Interacts with BRCA1.|||Neurons are resistant to amyloid-beta neurotoxicity. Significantly lower CASP12 expression in brain.|||Sumoylation at Lys-14 impairs catalytic activity. http://togogenome.org/gene/10090:Or9s18 ^@ http://purl.uniprot.org/uniprot/E9Q2B9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cbfb ^@ http://purl.uniprot.org/uniprot/Q08024 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CBF-beta family.|||Does not dimerize with the alpha subunit.|||Expressed in all tissues tested. Highest level in thymus, but also abundantly expressed in muscle, lung and brain.|||Forms the heterodimeric complex core-binding factor (CBF) with RUNX family proteins (RUNX1, RUNX2, and RUNX3). RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation (PubMed:18258917).|||Heterodimer with RUNX1, RUNX2 and RUNX3 (Probable). Interacts with COPRS. Found in a complex with PRMT5 and RUNX1 (PubMed:22193545).|||Major isoform.|||Nucleus http://togogenome.org/gene/10090:Rad51ap1 ^@ http://purl.uniprot.org/uniprot/Q8C551 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Highly expressed in 15 to 21 days postpartum (dpp) testes.|||Monomer; elongated monodisperse monomer (By similarity). Interacts (via C-terminal region) with RAD51; the interaction is direct (PubMed:9192668). Interacts (via SIM motif) with WDR48/UAF1; WDR48/UAF1 and RAD51AP1 cooperate together to stimulate RAD51-mediated homologous recombination (HR) (By similarity). Interacts (via WVPP motif) with DMC1; the interaction is direct (By similarity). Interacts with PALB2. Interacts with RAD52 (By similarity).|||Most abundantly expressed in testis (PubMed:9192668). Also expressed in spleen, thymus and bone marrow (PubMed:9192668). Not detected in heart, kidney or liver (PubMed:9192668).|||Nucleus|||Structure-specific DNA-binding protein involved in DNA repair by promoting RAD51-mediated homologous recombination. Acts by stimulating D-Loop formation by RAD51: specifically enhances joint molecule formation through its structure-specific DNA interaction and its interaction with RAD51. Binds single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures: has a strong preference for branched-DNA structures that are obligatory intermediates during joint molecule formation. Cooperates with WDR48/UAF1 to stimulate RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during homologous recombination and DNA repair. WDR48/UAF1 and RAD51AP1 also have a coordinated role in DNA-binding to promote USP1-mediated deubiquitination of FANCD2. Also involved in meiosis by promoting DMC1-mediated homologous meiotic recombination.|||Sumoylation with SUMO2/3 by NSMCE2/MMS21 promotes stabilization, possibly by preventing ubiquitination.|||telomere http://togogenome.org/gene/10090:Teddm3 ^@ http://purl.uniprot.org/uniprot/Q9CQH1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Membrane http://togogenome.org/gene/10090:Arid4a ^@ http://purl.uniprot.org/uniprot/F8VPQ2 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (PubMed:17043311, PubMed:23487765). May function as part of an mSin3A repressor complex (By similarity). Has no intrinsic transcriptional activity (PubMed:23487765). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (PubMed:17043311). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation (PubMed:23487765). Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (PubMed:23487765). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis (PubMed:18728284). May function as a leukemia suppressor (PubMed:18728284).|||Expressed in Sertoli cells of the testis.|||Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, BRMS1, HDAC1 and HDAC2 (By similarity). Interacts with BRMS1 (By similarity). Interacts with RB1 (By similarity). Interacts with ARID4B (PubMed:17043311). Interacts with AR (PubMed:23487765).|||Nucleus|||The function of the Tudor-knot domain, also named chromodomain-like, is uncertain. One study suggests that it mediates binding to lysine-methylated histone tails, with strongest affinity for H4K20me3 and H3K36me3. However, another study failed to find any interaction between this domain and histone H4K20me3 peptide.|||Viable and fertile, although females have reduced fertility (PubMed:17043311, PubMed:18728284). At two months of age, animals show abnormal blood cell production accompanied by mild anemia, leukopenia and thrombocytopenia. Hematologic abnormalities become progressively more severe with age (PubMed:18728284). Monocytosis is observed at 5 months onwards, along with splenomegaly and hepatomegaly (PubMed:18728284). Approximately 12% of animals develop acute myeloid leukemia (AML) and/or myeloid sarcoma (PubMed:18728284). Mortality increases rapidly from age 6 months onwards, with no survival past 22 months (PubMed:18728284). Expansion of hematopoietic stem cell and common myeloid progenitor cell populations, and their downstream lineage, is observed in bone marrow and spleen; the effect is most significant in spleen (PubMed:18728284). Bone marrow cells show altered patterns of histone methylation and significantly increased levels of both H3K4me3 and H3K9me3 (PubMed:18728284). Expression of HOXB3, HOXB5, HOXB6, HOXB8 and PITX2 in bone marrow cells is reduced (PubMed:18728284). No effect on histone methylation at the PWS/AS imprinting center (PubMed:17043311). Double knockouts with ARID4B heterozygotes show a more severe hematologic phenotype with 83% of animals progressing to AML, and with earlier age of onset (PubMed:18728284). In bone marrow cells, expression of FOXP3 is significantly reduced (PubMed:18728284). Males show progressive reduction in fertility from 2 months of age onwards, with reduced testis size and variable defects in seminal vesicle formation (PubMed:23487765). Spermatogenesis is partially blocked from the meiois II stage onwards leading to reduced numbers of mature spermatozoa (PubMed:23487765). Expression in testis of CLDN3, an androgen receptor-regulated gene, is significantly reduced (PubMed:23487765). Expression of PTGDS is also reduced, whereas expression of INHA and EMB is moderately increased (PubMed:23487765). Maternal-specific trimethylation of H4K20 and H3K9 at the PWS/AS imprinting center is significantly reduced (PubMed:17043311). http://togogenome.org/gene/10090:Defb34 ^@ http://purl.uniprot.org/uniprot/Q7TNV8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Only expressed in epididymis (caput, corpus and cauda).|||Secreted http://togogenome.org/gene/10090:Vmn1r54 ^@ http://purl.uniprot.org/uniprot/Q9EPB8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Cltrn ^@ http://purl.uniprot.org/uniprot/Q9ESG4 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CLTRN family.|||Cell membrane|||Deficient mice are viable and fertile but exhibit a severe defect in renal amino acid uptake due to down-regulation of apical amino acid transporters in the kidney (PubMed:17167413). Greater urine output, more dilute urine, a defect in urinary concentration, higher osmolar clearance and an increase in free water absorption, suggesting an osmotic diuresis (PubMed:16985211). Decreased urine osmolytes sodium and urea, presence of tyrosine and glutamine crystals in the urine, and increased excretion of amino acids in the urine, suggesting an aminoaciduria (PubMed:16985211). Decreased population of amino acid transporters SLC6A19, SLC3A1 and SLC7A9 in the renal cortical cell membrane (PubMed:16985211). Increased intracellular SLC1A1 levels (PubMed:16985211).|||Expressed on the apical surface of the proximal tubules in the renal cortex (at protein level) (PubMed:16985211). Kidney; collecting ducts and proximal tubule (PubMed:11278314, PubMed:17167413, PubMed:16985211). Pancreas; beta cells of islets (PubMed:16330323, PubMed:16330324). Expressed in the cerebral cortex, hippocampus, brainstem and cerebellum (PubMed:31520464).|||Glycosylated. Glycosylation is required for plasma membrane localization and for its cleavage by BACE2.|||Monomer (PubMed:16330324). Homodimer (PubMed:16330324). Homodimer; dimerization prevents CLTRN cleavage by BACE2 (PubMed:16330324). Interacts with SNAPIN (PubMed:16330323). Interacts with SLC6A18; this interaction regulates the trafficking of SLC6A18 to the cell membrane and its amino acid transporter activity (PubMed:17167413, PubMed:19478081). Interacts with SLC6A19; this interaction regulates the trafficking of SLC6A19 to the cell membrane and its amino acid transporter activity (PubMed:17167413). Interacts with SLC6A20B (PubMed:17167413).|||Plays an important role in amino acid transport by acting as binding partner of amino acid transporters SLC6A18 and SLC6A19, regulating their trafficking on the cell surface and their activity (PubMed:17167413, PubMed:16985211). May also play a role in trafficking of amino acid transporters SLC3A1 and SLC7A9 to the renal cortical cell membrane (PubMed:16985211). Regulator of SNARE complex function (PubMed:16330323). Stimulator of beta cell replication (PubMed:16330324).|||Proteolytically processed in pancreatic beta cells by BACE2 leading to the generation and extracellular release of soluble CLTRN, and a corresponding cell-associated C-terminal fragment which is later cleaved by gamma-secretase (PubMed:16330324, PubMed:21907142). This shedding process inactivates CLTRN (PubMed:16330324). Three cleavage sites have been identified for BACE2, two clustered sites after Phe-116 and Leu-118 and a more membrane proximal site at Phe-125; the preferred BACE2 cleavage site seems to be between Phe-125 and Leu-126, Phe-116 and Leu-118 act as alternative sites (By similarity).|||The cleavage site containing the double Phe-Phe motif acts as negative regulator of shedding by BACE2.|||Up-regulated by high glucose concentration in beta-cells (at protein level). http://togogenome.org/gene/10090:Rpl10a ^@ http://purl.uniprot.org/uniprot/Q5XJF6 ^@ Similarity ^@ Belongs to the universal ribosomal protein uL1 family. http://togogenome.org/gene/10090:Optc ^@ http://purl.uniprot.org/uniprot/E9PUR1|||http://purl.uniprot.org/uniprot/G3UVW2|||http://purl.uniprot.org/uniprot/Q14BF5|||http://purl.uniprot.org/uniprot/Q3U5A9|||http://purl.uniprot.org/uniprot/Q4KL49|||http://purl.uniprot.org/uniprot/Q920A0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.|||Expressed in cartilage (at protein level) (PubMed:29323130). Expressed in the vitreous collagen, inner limiting membrane, lens capsule, trabecular meshwork, anterior surface of the iris, the area adjacent to the nonpigmented ciliary epithelium, and weakly expressed in the retina of the eye (at protein level) (PubMed:22159013). Expressed in the nonpigmented ciliary epithelium of the eye (PubMed:11527931).|||Expressed in the presumptive ciliary body during development.|||Homodimer.|||Increased organization of cartilage collagen fibers featuring more smaller diameter fibers that are closely packed (PubMed:29323130). Dysregulation of small leucine-rich repeat proteoglycan superfamily members in cartilage, including an increase in Lum and Epyc, and a decrease in Fmod and Prelp (PubMed:29323130). In a surgical osteoarthritis model, a reduction in cartilage degradation and inflammatory markers, decreased loss of cartilage integrity, and reduced synovial membrane thickness (PubMed:29323130). Decrease in vitreous body vaso-obliteration upon hypoxia, and an increase in preretinal neovascularization upon restoration of normoxia (PubMed:22159013).|||Inhibits angiogenesis in the vitreous humor of the eye, and therefore represses neovascularization (PubMed:22159013). Binds collagen fibrils (By similarity). May be involved in collagen fiber organization via regulation of other members of the small leucine-rich repeat proteoglycan superfamily (PubMed:29323130).|||O-glycosylated.|||Proteolytically cleaved by MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, ADAMTS4, and ADAMTS5 (By similarity). Proteolytically cleaved by MMP13 (By similarity).|||Sulfated on tyrosine residues.|||extracellular matrix http://togogenome.org/gene/10090:Alkal1 ^@ http://purl.uniprot.org/uniprot/J3QPP8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ALKAL family.|||Cell membrane|||Cytokine that acts as a physiological ligand for receptor tyrosine kinase LTK, leading to its activation. Monomeric ALKAL1 binds to LTK, leading to LTK homodimerization and activation. In contrast to ALKAL2, does not act as a potent physiological ligand for ALK.|||Secreted http://togogenome.org/gene/10090:Rab36 ^@ http://purl.uniprot.org/uniprot/Q8CAM5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Golgi apparatus membrane|||Protein transport. Probably involved in vesicular traffic (By similarity). http://togogenome.org/gene/10090:Mrps11 ^@ http://purl.uniprot.org/uniprot/Q3U8Y1 ^@ Similarity ^@ Belongs to the universal ribosomal protein uS11 family. http://togogenome.org/gene/10090:R3hdm4 ^@ http://purl.uniprot.org/uniprot/Q4VBF2 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Fam13b ^@ http://purl.uniprot.org/uniprot/Q8K2H3 ^@ Similarity ^@ Belongs to the FAM13 family. http://togogenome.org/gene/10090:Serinc1 ^@ http://purl.uniprot.org/uniprot/A9CLV6|||http://purl.uniprot.org/uniprot/Q9QZI8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TDE1 family.|||Endoplasmic reticulum membrane|||Enhances the incorporation of serine into phosphatidylserine and sphingolipids.|||Highly expressed in the neuronal populations such as Purkinje cells in the cerebellum, brainstem and spinal motor neurons, locus coeruleus and raphe nuclei.|||Interacts with SPTLC1.|||Membrane http://togogenome.org/gene/10090:Or4c10 ^@ http://purl.uniprot.org/uniprot/Q8VGN6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Klhl18 ^@ http://purl.uniprot.org/uniprot/E9Q4F2 ^@ Disruption Phenotype|||Function|||Subunit|||Tissue Specificity ^@ Interacts with AURKA (By similarity). Interacts (via BTB domain) with CUL3 (By similarity). Interacts (via kelch repeats) with UNC119 (PubMed:31696965).|||Predominantly expressed in maturing and mature retinal photoreceptor cells.|||Retina-specific gene disruption leads to decreased light response in rod photoreceptor cells and mislocalization of alpha-transducin from the outer segment to the inner part of rod photoreceptors.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis (By similarity). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (By similarity). Regulates light- and dark-dependent alpha-transducin localization changes in rod photoreceptors through UNC119 ubiquitination and degradation (PubMed:31696965). Preferentially ubiquitinates the unphosphorylated form of UNC119 over the phosphorylated form (PubMed:31696965). In the presence of UNC119, under dark-adapted conditions alpha-transducin mislocalizes from the outer segment to the inner part of rod photoreceptors which leads to decreased photoreceptor damage caused by light (PubMed:31696965). http://togogenome.org/gene/10090:Cntnap5a ^@ http://purl.uniprot.org/uniprot/Q0V8T9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neurexin family.|||Expressed from 6 dpc in brain.|||Expressed in brain.|||May play a role in the correct development and proper functioning of the peripheral and central nervous system and be involved in cell adhesion and intercellular communication.|||Membrane http://togogenome.org/gene/10090:Fgf11 ^@ http://purl.uniprot.org/uniprot/A0A7U3L4H2|||http://purl.uniprot.org/uniprot/P70378|||http://purl.uniprot.org/uniprot/Q6NXW2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Brain and eye, and in a segmental pattern of the embryonic body wall. In adult olfactory bulb, hippocampus and most concentrated in Purkinje cell layer of the cerebellum.|||Nucleus|||Probably involved in nervous system development and function. http://togogenome.org/gene/10090:Tlr1 ^@ http://purl.uniprot.org/uniprot/B9EJ46|||http://purl.uniprot.org/uniprot/Q9EPQ1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Toll-like receptor family.|||Cell membrane|||Golgi apparatus|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||Interacts (via extracellular domain) with TLR2. TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand. The heterodimers form bigger oligomers in response to their corresponding ligands as well as further heterotypic associations with other receptors such as CD14 and/or CD36 (By similarity). Binds MYD88 (via TIR domain). Interacts with CNPY3 (PubMed:17998391).|||Membrane|||Membrane raft|||Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides.|||Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Forms the activation cluster TLR2:TLR1:CD14 in response to triacylated lipopeptides, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity). Acts as a coreceptor for M.tuberculosis lipoproteins LprG, LpqH and PhoS1 (pstS1), in conjunction with TLR2 and for some but not all lipoproteins CD14 and/or CD36. The lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712).|||phagosome membrane http://togogenome.org/gene/10090:Alox5ap ^@ http://purl.uniprot.org/uniprot/P30355 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAPEG family.|||Endoplasmic reticulum membrane|||Homotrimer. Interacts with LTC4S and ALOX5.|||Nucleus membrane|||Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes (By similarity).|||The C-terminal part after residue 140 is mostly disordered. http://togogenome.org/gene/10090:Cilk1 ^@ http://purl.uniprot.org/uniprot/Q9JKV2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 14.5 dpc, expressed in the brain cortex, including the cortical plate, intermediate zone, and ventricular and subventricular zones.|||Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-157 by CDK7/Cak1p increases kinase activity.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Has an essential role in ciliogenesis, particularly in neuronal and retinal progenitor cells (PubMed:24797473). Phosphorylates KIF3A (PubMed:24797473). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (PubMed:24797473, PubMed:24853502). May play a role in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling -dependent manner and this regulation requires its kinase activity (PubMed:25243405).|||Highly expressed in colon and lung, lower levels present in heart, esophagus, stomach, small intestine and ovary. Localizes to the crypt region of large and small intestine.|||Knockout mice manifest hydrocephalus, polydactyly, and delayed skeletal development. At cellular levels, ICK knockout results in abnormally elongated cilia and compromised SHH signaling.|||Nucleus|||cilium|||cilium basal body|||cytosol http://togogenome.org/gene/10090:Enpp5 ^@ http://purl.uniprot.org/uniprot/Q9EQG7 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.|||Binds 2 Zn(2+) ions per subunit.|||Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates (PubMed:28898552). Lacks lysopholipase D activity. May play a role in neuronal cell communication (By similarity).|||Expressed abundantly in the brain and kidney, and at lower levels in the liver.|||Membrane|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Zfp652 ^@ http://purl.uniprot.org/uniprot/Q5DU09 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Functions as a transcriptional repressor.|||Interacts with CBFA2T3.|||Nucleus http://togogenome.org/gene/10090:Ftdc1 ^@ http://purl.uniprot.org/uniprot/Q3UWK9 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Wdr45b ^@ http://purl.uniprot.org/uniprot/Q9CR39 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat PROPPIN family.|||Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and other phosphoinositides including PtdIns(3,5)P2, forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2. In the cellular response to starvation, may also function together with the TSC1-TSC2 complex and RB1CC1 in the inhibition of the mTORC1 signaling pathway.|||Interacts with the TSC1-TSC2 complex; stimulated upon starvation (By similarity). Interacts with RB1CC1 (PubMed:28561066). Interacts with ATG2A (By similarity).|||Lysosome|||Preautophagosomal structure|||The L/FRRG motif is required for recruitment to PtdIns3P. http://togogenome.org/gene/10090:Or6c7 ^@ http://purl.uniprot.org/uniprot/A0A1L1SV77 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ifrd2 ^@ http://purl.uniprot.org/uniprot/Q9D8U0 ^@ Function|||Similarity|||Subunit ^@ Associates with ribosomes; promoting ribosome inactivation.|||Belongs to the IFRD family.|||Ribosome-binding protein that acts as an inhibitor of mRNA translation by promoting ribosome inactivation (By similarity). Associates with the P- and E-sites of the ribosome and inserts a C-terminal helix into the mRNA exit channel to preclude translation (By similarity). http://togogenome.org/gene/10090:Tnfsf13b ^@ http://purl.uniprot.org/uniprot/A0A0U5J6R6|||http://purl.uniprot.org/uniprot/Q3KP92|||http://purl.uniprot.org/uniprot/Q9WU72 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response.|||Homotrimer. Isoform 2 heteromultimerizes with isoform 1, probably limiting the amount of functional isoform 1 on the cell surface.|||Isoform 2 is expressed in many myeloid cell lines.|||Isoform 2 is not efficiently shed from the membrane unlike isoform 1.|||Isoform 2 seems to inhibit isoform 1 secretion and bioactivity.|||Secreted|||The soluble form derives from the membrane form by proteolytic processing. http://togogenome.org/gene/10090:Mrpl12 ^@ http://purl.uniprot.org/uniprot/Q9DB15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the mitochondrial large ribosomal subunit, it plays a role in mitochondrial translation. Associates with mitochondrial RNA polymerase to activate transcription.|||Belongs to the bacterial ribosomal protein bL12 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity). Interacts with NOA1.|||Mitochondrion matrix http://togogenome.org/gene/10090:Faf1 ^@ http://purl.uniprot.org/uniprot/P54731 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CDT1 and ATPase VCP/p97. Interacts (via UBA domain) with FAS (via death domain). Interacts (via UBA domain) with NLRP12 (via DAPIN/PYRIN domain).|||Nucleus|||Ubiquitin-binding protein (By similarity). Required for the progression of DNA replication forks by targeting DNA replication licensing factor CDT1 for degradation (By similarity). Potentiates but cannot initiate FAS-induced apoptosis (PubMed:8524870). http://togogenome.org/gene/10090:Gstp3 ^@ http://purl.uniprot.org/uniprot/Q8VC73 ^@ Function|||Similarity|||Subunit ^@ Belongs to the GST superfamily. Pi family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Homodimer. http://togogenome.org/gene/10090:Slc4a1 ^@ http://purl.uniprot.org/uniprot/P04919|||http://purl.uniprot.org/uniprot/Q3TZ29|||http://purl.uniprot.org/uniprot/Q53ZN9 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A dimer in solution, but in its membrane environment, it exists primarily as a mixture of dimers and tetramers and spans the membrane asymmetrically. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with STOM; this interaction positively regulates SLC4A1 activity. Interacts with GYPA; a GYPA monomer is bound at each end of the SLC4A1 dimer forming an heterotetramer. Three SLC4A1 dimers (Band 3-I, Band 3-II and Band 3-III) participates in the ankyrin-1 complex. Interacts (via the cytoplasmic domain) with EPB42; this interaction is mediated by the SLC4A1 Band 3-I dimer. Interacts (via the cytoplasmic domain) directly with ANK1; this interaction is mediated by the SLC4A1 Band 3-II and Band 3-III dimers.|||Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Detected in erythrocytes (at protein level).|||Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein. Component of the ankyrin-1 complex of the erythrocyte membrane; required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin. Functions as a transporter that mediates the 1:1 exchange of inorganic anions across the erythrocyte membrane. Mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine.|||Gypa is not incorporated in the erythrocyte membrane.|||Interacts with TMEM139.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Pgap2 ^@ http://purl.uniprot.org/uniprot/Q3TQR0|||http://purl.uniprot.org/uniprot/Q3U6W8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PGAP2 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with PGAP2IP.|||Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface (By similarity).|||Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface.|||Membrane http://togogenome.org/gene/10090:Cel ^@ http://purl.uniprot.org/uniprot/Q3V2H7|||http://purl.uniprot.org/uniprot/Q64285 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by bile salts such as sodium taurocholate.|||Belongs to the type-B carboxylesterase/lipase family.|||Catalyzes the hydrolysis of a wide range of substrates including cholesteryl esters, phospholipids, lysophospholipids, di- and tri-acylglycerols, and fatty acid esters of hydroxy fatty acids (FAHFAs) (PubMed:27509211). Preferentially hydrolyzes FAHFAs with the ester bond further away from the carboxylate. Unsaturated FAHFAs are hydrolyzed more quickly than saturated FAHFAs (PubMed:27509211). Has an essential role in the complete digestion of dietary lipids and their intestinal absorption, along with the absorption of fat-soluble vitamins (By similarity).|||EXpressed by eosinophils.|||Interacts with CLC.|||Secreted http://togogenome.org/gene/10090:Chchd3 ^@ http://purl.uniprot.org/uniprot/Q9CRB9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MICOS complex subunit Mic19 family. Metazoan Mic19 subfamily.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Has also been shown to function as a transcription factor which binds to the BAG1 promoter and represses BAG1 transcription. Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex (By similarity). Interacts with HSPA1A/HSPA1B and OPA1, preferentially with the soluble OPA1 form.|||Cytoplasm|||Mitochondrion|||Mitochondrion inner membrane|||Nucleus http://togogenome.org/gene/10090:Vsig8 ^@ http://purl.uniprot.org/uniprot/Q6P3A4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Nudt4 ^@ http://purl.uniprot.org/uniprot/Q4FJR0|||http://purl.uniprot.org/uniprot/Q8R2U6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Nudix hydrolase family. DIPP subfamily.|||Binds 3 Mg(2+) or Mn(2+) ions per subunit.|||Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction (By similarity). Can also catalyze the hydrolysis of diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) but not diadenosine 5',5'''-P1,P5-pentaphosphate (Ap5A) and the major reaction products are ADP and p4a from Ap6A (By similarity). Also able to hydrolyze 5-phosphoribose 1-diphosphate (By similarity). Does not play a role in U8 snoRNA decapping activity (PubMed:16141072). Binds U8 snoRNA (PubMed:16141072).|||Cytoplasm http://togogenome.org/gene/10090:Gpr37 ^@ http://purl.uniprot.org/uniprot/Q9QY42 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Forms a complex with PRKN, STUB1 and HSP70. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN, thus facilitating PRKN-mediated GPR37 ubiquitination. Interacts with PACRG (By similarity).|||Receptor for the neuroprotective and glioprotective factor prosaposin. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade (By similarity).|||Ubiquitinated by PRKN in the presence of ubiquitin-conjugating enzymes in the endoplasmic reticulum. http://togogenome.org/gene/10090:Gabra6 ^@ http://purl.uniprot.org/uniprot/P16305 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA6 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Binds UBQLN1.|||Only found in cerebellar granule cells.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Mphosph9 ^@ http://purl.uniprot.org/uniprot/A6H5Y1 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Golgi apparatus membrane|||Interacts with CCP110, CEP97 and KIF24.|||Knockout mice show decreased body weight when compared with wild-type mice around 1 month after birth (PubMed:30375385). An increased percentage of ciliated cells in the proximal and distal tubules is observed in the kidneys of knockout mice at 1 and 4 months after birth (PubMed:30375385).|||Negatively regulates cilia formation by recruiting the CP110-CEP97 complex (a negative regulator of ciliogenesis) at the distal end of the mother centriole in ciliary cells (PubMed:30375385). At the beginning of cilia formation, MPHOSPH9 undergoes TTBK2-mediated phosphorylation and degradation via the ubiquitin-proteasome system and removes itself and the CP110-CEP97 complex from the distal end of the mother centriole, which subsequently promotes cilia formation (By similarity).|||TTBK2-mediated phosphorylation at Ser-710 and Ser-717, promotes its ubiquitination at Lys-713 leading to proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex from the mother centrioles, promoting the initiation of ciliogenesis (By similarity). Phosphorylated in M (mitotic) phase (By similarity).|||Ubiquitinated at Lys-713, leading to proteasomal degradation.|||centriole|||centrosome http://togogenome.org/gene/10090:Relb ^@ http://purl.uniprot.org/uniprot/Q04863 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both N- and C-terminal domains are required for transcriptional activation.|||Component of the NF-kappa-B RelB-p50 complex. Component of the NF-kappa-B RelB-p52 complex (By similarity). Self-associates; the interaction seems to be transient and may prevent degradation allowing for heterodimer formation p50 or p52. Interacts with NFKB1/p50, NFKB2/p52 and NFKB2/p100. Interacts with NFKBID. Interacts with BMAL1 and the interaction is enhanced in the presence of CLOCK.|||Expressed in intestine, thymus and spleen. Undetectable in liver, bome marrow, kidney and testis.|||NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49 (By similarity). As a member of the NUPR1/RELB/IER3 survival pathway, may allow the development of pancreatic intraepithelial neoplasias. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function (By similarity).|||Nucleus|||Phosphorylation at 'Thr-103' and 'Ser-573' is followed by proteasomal degradation.|||centrosome http://togogenome.org/gene/10090:Itga6 ^@ http://purl.uniprot.org/uniprot/Q61739|||http://purl.uniprot.org/uniprot/Q6PEE8|||http://purl.uniprot.org/uniprot/Q8CC06 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin alpha chain family.|||Cell membrane|||Expressed at low levels in normal skin tissue with elevated levels in skin tumors.|||Heterodimer of an alpha and a beta subunit (PubMed:8081870). The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond (PubMed:8081870). Alpha-6 associates with either beta-1 (ITGB1) or beta-4 (ITGB4) to form ITGA6:ITGB1 and ITGA6:ITGB4, respectively (PubMed:8081870, PubMed:10634791). ITGA6:ITGB1 is found in a complex with CD9; interaction takes place in oocytes and is involved in sperm-egg fusion (PubMed:10634791). ITGA6:ITGB4 is found in a ternary complex with NRG1 and ERBB3 (By similarity). ITGA6:ITGB4 is found in a ternary complex with IGF1 and IGF1R (By similarity). ITGA6:ITGB4 interacts with IGF2 (By similarity). Interacts with ADAM9 (PubMed:10825303). Interacts with RAB21 (By similarity). Interacts with MDK. ITGA6:ITGB1 interacts with MDK; this interaction mediates MDK-induced neurite outgrowth (By similarity).|||Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (PubMed:8081870). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (PubMed:10634791). Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (PubMed:8673141). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (By similarity). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (By similarity). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (By similarity).|||Isoforms containing segment A, but not segment B, are the major targets for PMA-induced phosphorylation. Phosphorylation occurs on 'Ser-1064' of isoform alpha-6X1A. Phosphorylation is not required for the induction of integrin alpha-6A/beta-1 high affinity but may reduce the affinity for ligand (By similarity).|||Membrane|||Mice expressing a null mutation of the alpha-6 subunit gene die soon after birth and develop severe blistering (PubMed:8673141). The blisters are due to separation of the basal epithelial cells from a normally formed basement membrane (PubMed:8673141).|||Palmitoylation by DHHC3 enhances stability and cell surface expression.|||Undergoes PLAU-mediated cleavage at residues Arg-595-596-Arg in a time-dependent manner to produce processed integrin alpha-6 (alpha6p). http://togogenome.org/gene/10090:Pcx ^@ http://purl.uniprot.org/uniprot/E9QPD7|||http://purl.uniprot.org/uniprot/G5E8R3|||http://purl.uniprot.org/uniprot/Q3UFS6 ^@ Function ^@ Catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. http://togogenome.org/gene/10090:Kdelr2 ^@ http://purl.uniprot.org/uniprot/Q9CQM2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ERD2 family.|||Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).|||COPI-coated vesicle membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Membrane receptor that binds the K-D-E-L sequence motif in the C-terminal part of endoplasmic reticulum resident proteins and maintains their localization in that compartment by participating to their vesicle-mediated recycling back from the Golgi (By similarity). Binding is pH dependent, and is optimal at pH 5-5.4 (By similarity). http://togogenome.org/gene/10090:Hrh3 ^@ http://purl.uniprot.org/uniprot/P58406|||http://purl.uniprot.org/uniprot/Q3USH0|||http://purl.uniprot.org/uniprot/Q540P3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist) (By similarity). http://togogenome.org/gene/10090:Trarg1 ^@ http://purl.uniprot.org/uniprot/Q8C838 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||Cell membrane|||Endomembrane system|||Expressed specifically in white and brown adipose tissues.|||Interacts with SLC2A4; the interaction is required for proper SLC2A4 reacycling after insulin stimulation.|||Mutant adipocytes show reduced glucose uptake in response to an insulin stimulus (PubMed:26629404). Knockout animals placed on high-fat diet along with wild-type littermates exhibit an increased weight gain, significant elevated blood insulin and glucose levelswith insulin resistance (PubMed:26629404).|||Regulates insulin-mediated adipose tissue glucose uptake and transport by modulation of SLC2A4 recycling. Not required for SLC2A4 membrane fusion upon an initial stimulus, but rather is necessary for proper protein recycling during prolonged insulin stimulation.|||Target gene of PPARG, expression is induced upon PPARG activation (PubMed:26629404, PubMed:26240143). Expression is inhibited by TNF (PubMed:26240143).|||perinuclear region http://togogenome.org/gene/10090:Scara5 ^@ http://purl.uniprot.org/uniprot/Q8K299 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCARA5 family.|||Cell membrane|||Expressed in the testis, trachea, lung, bladder and small intestine; especially in epithelial cells associated with mucosal surfaces.|||Ferritin receptor that mediates non-transferrin-dependent delivery of iron. Mediates cellular uptake of ferritin-bound iron by stimulating ferritin endocytosis from the cell surface with consequent iron delivery within the cell. Delivery of iron to cells by ferritin is required for the development of specific cell types, suggesting the existence of cell type-specific mechanisms of iron traffic in organogenesis, which alternatively utilize transferrin or non-transferrin iron delivery pathways. Ferritin mediates iron uptake in capsule cells of the developing kidney. Preferentially binds ferritin light chain (FTL) compared to heavy chain (FTH1).|||Homotrimer. http://togogenome.org/gene/10090:Uchl5 ^@ http://purl.uniprot.org/uniprot/Q9WUP7 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by ADRM1. Inhibited by interaction with NFRKB (By similarity).|||Belongs to the peptidase C12 family.|||Component of the 19S (PA700) regulatory complex of the 26S proteasome. Interacts with ADRM1 and NFRKB. Component of the INO80 complex; specifically part of a complex module associated with N-terminus of INO80 (By similarity).|||Cytoplasm|||Nucleus|||Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1 (By similarity). http://togogenome.org/gene/10090:Nefm ^@ http://purl.uniprot.org/uniprot/A0A0R4J036|||http://purl.uniprot.org/uniprot/P08553 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the sciatic nerve (at protein level).|||Forms heterodimers with NEFL; which can further hetero-oligomerize (in vitro) (By similarity). Forms heterodimers with INA (in vitro) (By similarity).|||Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks (PubMed:22723690).|||Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.|||Phosphorylation seems to play a major role in the functioning of the larger neurofilament polypeptides (NF-M and NF-H), the levels of phosphorylation being altered developmentally and coincidentally with a change in the neurofilament function.|||There are a number of repeats of the tripeptide K-S-P, NFM is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFM results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber.|||axon|||cytoskeleton http://togogenome.org/gene/10090:Cfap418 ^@ http://purl.uniprot.org/uniprot/Q3UJP5 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in multiple tissues, including the brain, kidney, lung, spleen, heart, trachea and testis (PubMed:29440555). Expressed in the retina (at protein level) (PubMed:22177090, PubMed:29440555).|||Interacts (via N-terminus) with FAM161A (via central region); the interaction is direct.|||May be involved in photoreceptor outer segment disk morphogenesis.|||No visible phenotype. However mice exhibit progressive and simultaneous degeneration of rod and cone photoreceptors (PubMed:29440555).|||Photoreceptor inner segment http://togogenome.org/gene/10090:Mrps22 ^@ http://purl.uniprot.org/uniprot/Q9CXW2 ^@ Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS22 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Heterozygous MRPS22 knockout mice are fertile and show no overt abnormalities. Homozygous MRPS22 knockout results in embryonic lethality.|||Mitochondrion http://togogenome.org/gene/10090:Nqo2 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VL95|||http://purl.uniprot.org/uniprot/Q9CVF5|||http://purl.uniprot.org/uniprot/Q9JI75 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD(P)H dehydrogenase (quinone) family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Homodimer.|||The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.|||Uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor. http://togogenome.org/gene/10090:Naif1 ^@ http://purl.uniprot.org/uniprot/Q6PFD7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAIF1 family.|||Induces apoptosis.|||Interacts with HARBI1.|||Nucleus http://togogenome.org/gene/10090:Samd4 ^@ http://purl.uniprot.org/uniprot/A0A2D0VMX2|||http://purl.uniprot.org/uniprot/Q8CBY1 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Aberrant splicing.|||Acts as a translational repressor of SRE-containing messengers.|||Belongs to the SMAUG family.|||Cytoplasm|||Expressed in brain (at protein level).|||dendrite|||synaptosome http://togogenome.org/gene/10090:Mmd2 ^@ http://purl.uniprot.org/uniprot/Q3V1Z9|||http://purl.uniprot.org/uniprot/Q8R189 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ADIPOR family.|||Expressed in the testicular cords at 13.5 dpc.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Anks1b ^@ http://purl.uniprot.org/uniprot/A0A0R4J2A6|||http://purl.uniprot.org/uniprot/A0A0R4J2A8|||http://purl.uniprot.org/uniprot/E9QPP6|||http://purl.uniprot.org/uniprot/Q8BIZ1|||http://purl.uniprot.org/uniprot/Q8BZM2|||http://purl.uniprot.org/uniprot/S4R1H2|||http://purl.uniprot.org/uniprot/S4R2I2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with EPHA8. Isoform 2 interacts with COIL (By similarity).|||Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells.|||Nucleus|||Postsynaptic density|||dendritic spine http://togogenome.org/gene/10090:Golim4 ^@ http://purl.uniprot.org/uniprot/Q8BXA1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GOLIM4 family.|||Endosome membrane|||Expressed by spermatozoa (at protein level).|||Golgi stack membrane|||Membrane|||N-glycosylated; N-glycans are of the complex type and modified by sialic acid residues.|||O-glycosylated; modified by sialic acid residues.|||Phosphorylated by c-AMP-dependent kinases most probably in its lumenal part.|||Plays a role in endosome to Golgi protein trafficking; mediates protein transport along the late endosome-bypass pathway from the early endosome to the Golgi. http://togogenome.org/gene/10090:Rpgrip1 ^@ http://purl.uniprot.org/uniprot/Q9EPQ2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RPGRIP1 family.|||Expressed in the retina (at protein level).|||Interacts with NPHP4. Interacts with NEK4 (By similarity). Forms homodimers and elongated homopolymers (PubMed:12651948). Interacts with RPGR (PubMed:11104772). Interacts with SPATA7 (PubMed:25398945, PubMed:29899041). Interacts with CEP290/NPHP6; mediating the association between RPGR and CEP290/NPHP6 (By similarity).|||May function as scaffolding protein. Required for normal location of RPGR at the connecting cilium of photoreceptor cells. Required for normal disk morphogenesis and disk organization in the outer segment of photoreceptor cells and for survival of photoreceptor cells.|||Mutant mice are born at the expected Mendelian rate, appear healthy and are fertile. They have initially a complete set of photoreceptor cells in the retina, but the photoreceptor cells present defects in the outer segments indicative of cell death, and loss of photoreceptor cells is almost complete after three months.|||The C2 domain does not bind calcium ions, and does not bind phosphoinositides.|||cilium http://togogenome.org/gene/10090:Otud6b ^@ http://purl.uniprot.org/uniprot/Q8K2H2 ^@ Disruption Phenotype|||Function|||Induction|||Subunit|||Tissue Specificity ^@ Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1 (By similarity). May associate with the protein synthesis initiation complex and modify its ubiquitination to repress translation (By similarity). May also repress DNA synthesis and modify different cellular targets thereby regulating cell growth and proliferation (By similarity). May also play a role in proteasome assembly and function (By similarity).|||Interacts with the eukaryotic translation initiation factor 4F complex.|||Mice are sub-viable and die between embryonic day 18.5 and shortly after birth. They show intrauterine growth retardation and a high percentage of ventricular septal cardiac defects.|||Ubiquitously expressed. Expression is observed in several organ systems including the cardiovascular, digestive, central and peripheral nervous and musculoskeletal systems.|||Up-regulated by cytokines but followed by a rapid decline in B lymphocytes. http://togogenome.org/gene/10090:Nlrc5 ^@ http://purl.uniprot.org/uniprot/C3VPR6 ^@ Caution|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NLRP family.|||By interferon gamma. By LPS and viruses (at protein level).|||Cytoplasm|||Due to intron retention.|||Expressed in spleen, thymus and lung.|||Interacts with CHUK and IKBKB; prevents CHUK and IKBKB phosphorylation and inhibits their kinase activity. Interacts with RIGI and IFIH1; blocks the interaction of MAVS to RIGI.|||Probable regulator of the NF-kappa-B and type I interferon signaling pathways. May also regulate the type II interferon signaling pathway. Plays a role in homeostatic control of innate immunity and in antiviral defense mechanisms.|||Supposed to contain a CARD domain at the N-terminus. However, this domain is not detected by Pfam, PROSITE or SMART. Has a weak similarity with a DAPIN domain. http://togogenome.org/gene/10090:Phb2 ^@ http://purl.uniprot.org/uniprot/O35129|||http://purl.uniprot.org/uniprot/Q3V235 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the prohibitin family.|||Cell membrane|||Cytoplasm|||In B cells, expression is increased by CD40 engagement (at protein level).|||In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (PubMed:31819158). Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration. Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity (PubMed:11302691, PubMed:20959514). Has a key role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117).|||In the nucleus, serves as transcriptional co-regulator (Probable). Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity (PubMed:12878603, PubMed:15140878).|||In the plasma membrane, is involved in IGFBP6-induced cell migration (By similarity). Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (PubMed:23241883).|||LC3-interaction region (LIR) is required for interaction with MAP1LC3B/LC3-II and for Parkin-mediated mitophagy.|||Membrane|||Mitochondrion inner membrane|||Nucleus|||Phosphorylated. Tyrosine phosphorylation is indirectly stimulated by IGFBP6.|||Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus.|||The mitochondrial prohibitin complex consists of two subunits (PHB1 and PHB2), assembled into a membrane-associated ring-shaped supercomplex of approximately 1 mDa (PubMed:20959514, PubMed:28017329, PubMed:31522117). Interacts with ESR1, HDAC1 and HDAC5 (PubMed:12878603, PubMed:15140878). Interacts with ZNF703 (By similarity). Interacts with STOML2 (By similarity). Interacts with ARFGEF3 (By similarity). Interacts with SPHK2 (PubMed:20959514). Interacts with COX4I1; the interaction associates PHB2 with COX (PubMed:20959514). Interacts with MAP1LC3B (membrane-bound form LC3-II); the interaction is direct and upon mitochondrial depolarization and proteasome-dependent outer membrane rupture (By similarity). Interacts with IGFBP6 (via C-terminal domain) (By similarity). Interacts with CLPB (By similarity). Interacts with CD86 (via cytoplasmic domain); the interactions increases after priming with CD40 (PubMed:23241883). Interacts with AFG3L2 (PubMed:24856930). Interacts with DNAJC19 (PubMed:24856930).|||Throughout gestation, highly expressed in brown fat, heart, liver, developing renal tubules and neurons, and detected at lower levels in tissues such as lung and exocrine pancreas.|||Widely expressed in different tissues. http://togogenome.org/gene/10090:Pwp2 ^@ http://purl.uniprot.org/uniprot/Q2M1K2|||http://purl.uniprot.org/uniprot/Q8BU03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat PWP2 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Prss12 ^@ http://purl.uniprot.org/uniprot/O08762 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Most abundant in cerebral cortex, hippocampus and amygdala.|||Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations.|||Secreted http://togogenome.org/gene/10090:Tex101 ^@ http://purl.uniprot.org/uniprot/Q9JMI7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasmic vesicle|||Detected in prospermatogonia in embryos after 14 days of development and until 8 days after birth. Not detectable in spermatogonia from over 10 day old animals. Highly expressed in spermatocytes and spermatids from 12-28 day old animals, but not in spermatogonia. Detected in embryonic ovary after 14 days of development and in newly born animals. Expression is much reduced in ovary from 4 day old animals, and not detectable thereafter. Not detectable in oocytes that are surrounded by follicular cells.|||Detected in testis and ovary (PubMed:11207211, PubMed:15689535, PubMed:15917346, PubMed:16388701, PubMed:23969891). Expressed in spermatocytes, spermatids and testicular spermatozoa, but not in spermatogonia or interstitial cells (PubMed:18620756). Expressed abundantly in testicular germ cells (TGCs) but mostly disappeared from epididymal spermatozoa (PubMed:23633567).|||Interacts with VAMP3 (PubMed:16678124). Interacts with LY6K (PubMed:18503752). Interacts with DPEP3; co-localized on the cell surface of spermatocytes, spermatids, and testicular spermatozoa, co-localized only in cytoplasmic droplets of caput and corpus epididymal sperm (PubMed:21724266). Interacts with ADAM3; co-localized on sperm surface (PubMed:23633567, PubMed:23969891). Interacts with ADAM5 (PubMed:23969891).|||Knockout Tex101 mice are viable and show no overt developmental abnormalities. Males are infertile.|||Membrane raft|||N-glycosylated; by high mannose and/or biantennary complex and/or certain types of hybrid oligosaccharides; possesses different oligosaccharides chains according to its subcellular localization in the testis.|||Plays a role in fertilization by controlling binding of sperm to zona pellucida and migration of spermatozoa into the oviduct probably through molecule adhesion ADAM3 (PubMed:23633567, PubMed:23969891). May play a role in signal transduction and promote protein tyrosine phosphorylation (By similarity).|||Secreted|||Sheds from membrane raft by ACE and released from the cell surface of epididymal sperm while it passes through the caput epididymis leading to disappearance of TEX101 on spermatozoa; is essential to produce fertile spermatozoa.|||acrosome http://togogenome.org/gene/10090:Ell2 ^@ http://purl.uniprot.org/uniprot/Q3UKU1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ELL/occludin family.|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts with AFF4; the interaction is direct and leads to stabilize ELL2 and prevent ELL2 ubiquitination. Interacts with EAF1 and EAF2 (By similarity).|||Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (By similarity). Plays a role in immunoglobulin secretion in plasma cells: directs efficient alternative mRNA processing, influencing both proximal poly(A) site choice and exon skipping, as well as immunoglobulin heavy chain (IgH) alternative processing. Probably acts by regulating histone modifications accompanying transition from membrane-specific to secretory IgH mRNA expression.|||Nucleus|||Ubiquitinated by SIAH1, leading to its degradation by the proteasome. Interaction with AFF4 stabilizes ELL2 and prevents ELL2 ubiquitination (By similarity). http://togogenome.org/gene/10090:Sec61a1 ^@ http://purl.uniprot.org/uniprot/P61620 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SecY/SEC61-alpha family.|||Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides. May cooperate with auxiliary protein SEC62, SEC63 and HSPA5/BiP to enable post-translational transport of small presecretory proteins. The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex. The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER. Controls the passive efflux of calcium ions from the ER lumen to the cytosol through SEC61 channel, contributing to the maintenance of cellular calcium homeostasis (By similarity). Plays a critical role in nephrogenesis, specifically at pronephros stage (PubMed:27392076).|||Endoplasmic reticulum membrane|||The SEC61 channel-forming translocon complex consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63 (By similarity). The SEC61 channel associates with the multi-pass translocon (MPT) complex (By similarity).|||When transfected in zebrafish, is able to rescue the pronephric kidney tubule development phenotype of the morpholino knockdown of the orthologous protein. http://togogenome.org/gene/10090:Cdc42ep1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0S1|||http://purl.uniprot.org/uniprot/Q91W92 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BORG/CEP family.|||Endomembrane system|||Interacts with RHOQ and CDC42, in a GTP-dependent manner.|||Probably involved in the organization of the actin cytoskeleton. Induced membrane extensions in fibroblasts (By similarity).|||The CRIB domain mediates interaction with CDC42.|||cytoskeleton http://togogenome.org/gene/10090:Dbi ^@ http://purl.uniprot.org/uniprot/P31786 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ACBP family.|||Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor.|||Endoplasmic reticulum|||Golgi apparatus|||Monomer. http://togogenome.org/gene/10090:Corin ^@ http://purl.uniprot.org/uniprot/Q9Z319 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A disulfide bond links the activated corin protease fragment and the N-terminal propeptide. The disulfide bond also links the activated corin protease fragment with Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment (By similarity).|||Activated through proteolytic processing by a trypsin-like protease; cleaved into a N-terminal propeptide and an activated corin protease fragment. Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment is produced by cleavage by ADAM10. Cleavage by ADAM10 to produce soluble 180 kDa soluble fragment takes place after the transmembrane region and before FZ 1 (By similarity).|||Belongs to the peptidase S1 family.|||Cell membrane|||Corin is disrupted in C57BL/6-Kit(W-sh/W-sh) mice, a genetic inversion used as mast cell-deficient model. Phenotypes in C57BL/6-Kit(W-sh/W-sh) mice are mainly due to the absence of Kit, a receptor for mast cell development. The absence of Corin probably leads to immediate significant cardiac hypertrophy and contractile dysfunction in response to pressure overload (PubMed:21903139).|||Highly expressed in heart. Also expressed in pregnant uterus.|||Mice develop normally, are viable and fertile but develop hypertension. They display increased body weight associated with impaired maturation of pro-NPPA which can be restored by injection of Corin. Spontaneous and salt-sensitive hypertension exacerbated during pregnancy is also noticed. A cardiac hypertrophy is also detected together with a decline in cardiac function later in life (PubMed:15637153). Blood pressure on a high-salt diet is significantly increased: knockout mice show an impairment of urinary sodium excretion and an increase in body weight, but no elevation of plasma renin or serum aldosterone levels (PubMed:22418978). Conditional knockout mice which express Corin in heart only do not display any visible phenotype in non-pregnant mice. In contrast, pregnant conditional knockout mice develop high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodeling are markedly impaired (PubMed:22437503).|||N-glycosylated; required for processing and activation.|||Secreted|||Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) processing (PubMed:11884416, PubMed:15637153). Converts through proteolytic cleavage the non-functional propeptide NPPA into the active hormone, thereby regulating blood pressure in heart and promoting natriuresis, diuresis and vasodilation (PubMed:11884416, PubMed:15637153, PubMed:22418978). Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus (PubMed:22437503). Also acts as a regulator of sodium reabsorption in kidney (PubMed:20613715, PubMed:22418978). May also process pro-NPPB the B-type natriuretic peptide (By similarity). http://togogenome.org/gene/10090:Rinl ^@ http://purl.uniprot.org/uniprot/Q80UW3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic vesicle|||Detected in thymus and spleen (at protein level). Detected in lung, liver, kidney, spleen, thymus and skeletal muscle.|||Guanine nucleotide exchange factor (GEF) for RAB5A and RAB22A that activates RAB5A and RAB22A by exchanging bound GDP for free GTP. Plays a role in endocytosis via its role in activating Rab family members.|||Interacts with RAB5A, RAB22A and MUSK.|||ruffle http://togogenome.org/gene/10090:Mid2 ^@ http://purl.uniprot.org/uniprot/B1AVF4|||http://purl.uniprot.org/uniprot/Q9QUS6 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with microtubules in a manner that is dependent on the C-terminal B30.2 domain.|||At 10.5 dpc, a very low level is mostly confined to the central nervous system and the developing heart and kidney, while at later stages it is present in other organ systems.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays a role in microtubule stabilization. Mediates the 'Lys-48'-linked polyubiquitination of LRRK2 to drive its localization to microtubules and its proteasomal degradation in neurons. This ubiquitination inhibits LRRK2 kinase activation by RAB29.|||Homodimer or heterodimer with MID1. Interacts with IGBP1.|||It is uncertain whether Met-1 or Met-21 is the initiator.|||Low abundance in brain and lung, with even lower levels in heart, liver, and kidney.|||Phosphorylated on serine and threonine residues.|||The tripartite motif (RBCC; RING- and B box-type zinc fingers and coiled coil domains) mediates dimerization.|||cytoskeleton http://togogenome.org/gene/10090:Or8g20 ^@ http://purl.uniprot.org/uniprot/Q9EQB8|||http://purl.uniprot.org/uniprot/Q9Z1V5 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Snw1 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1E2|||http://purl.uniprot.org/uniprot/Q3TM37|||http://purl.uniprot.org/uniprot/Q9CSN1|||http://purl.uniprot.org/uniprot/Q9CV75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNW family.|||Identified in the spliceosome C complex (By similarity). Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs). Component of the minor spliceosome, which splices U12-type introns (By similarity). Interacts with SKI, SMAD2,SMAD3, RBPJ, RB1, PABPN1, MAGEA1, SIRT1, FOXN3, U2AF2, PPIL1, DAXX and ATP1B4. Interacts with VDR and RXRA; preferentially associates with VDR:RXRA heterodimers. Interacts with NCOR2. Interacts with MAML1. Interacts with NOTCH1 NICD; the interaction involves multimerized NOTCH1 NICD. Forms a complex with NOTCH1 NICD and MAML1; the association is dissociated by RBPJ. Associates with positive transcription elongation factor b (P-TEFb). Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN (By similarity).|||Identified in the spliceosome C complex.|||Involved in pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). Required in the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD.|||Involved in pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Gm94 ^@ http://purl.uniprot.org/uniprot/Q3V2D2 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Scgb1a1 ^@ http://purl.uniprot.org/uniprot/Q06318|||http://purl.uniprot.org/uniprot/Q3UKV9 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiparallel homodimer; disulfide-linked (By similarity). Interaction with LMBR1L is controversial (By similarity).|||Appears on the eighteenth day of gestation in the airway epithelium.|||Belongs to the secretoglobin family.|||Binds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.|||By glucocorticoids.|||Club cells (nonciliated cells of the surface epithelium of the pulmonary airways).|||Secreted http://togogenome.org/gene/10090:Cebpd ^@ http://purl.uniprot.org/uniprot/B9EIA9|||http://purl.uniprot.org/uniprot/Q00322|||http://purl.uniprot.org/uniprot/Q3UE64 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. C/EBP subfamily.|||Binds DNA as a homodimer and as a heterodimer. Can form stable heterodimers with CEBPA, CEBPB and CEBPE (PubMed:1884998). Directly interacts with SPI1/PU.1; this interaction does not affect DNA-binding properties of each partner (PubMed:7594592). Interacts with PRDM16 (PubMed:19641492).|||Nucleus|||Transcription activator that recognizes two different DNA motifs: the CCAAT homology common to many promoters and the enhanced core homology common to many enhancers (PubMed:7594592, PubMed:19641492). Important transcription factor regulating the expression of genes involved in immune and inflammatory responses. Transcriptional activator that enhances IL6 transcription alone and as heterodimer with CEBPB (By similarity). http://togogenome.org/gene/10090:Sema3f ^@ http://purl.uniprot.org/uniprot/O88632 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Expressed ubiquitously in adulthood. During embryogenesis, expressed in subregions of the central nervous system and various other tissues like skin, kidney, lung and intestine.|||Secreted http://togogenome.org/gene/10090:Nlrp12 ^@ http://purl.uniprot.org/uniprot/E9Q5R7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NLRP family.|||Cytoplasm|||Interacts (via pyrin domain) with ASC. Interacts (via pyrin domain) with FAF1 (via UBA domain) (By similarity). Interacts with MAP3K14; this interaction promotes proteasomal degradation of MAP3K14 (By similarity). Interacts with NOD2; this interaction promotes degradation of NOD2 through the ubiquitin-proteasome pathway (PubMed:30559449). Interacts with HSPA1A and HSPA8 (By similarity). Interacts with HSP90AA1 (PubMed:30559449). Interacts with TRIM25; this interaction inhibits RIGI-mediated signaling pathway (By similarity).|||Mainly expressed in dendritic cells (DCs) and neutrophils.|||NLRP12-deficient mice exhibit attenuated inflammatory responses due to significantly reduced capacity of dendritic cells to migrate to draining lymph nodes (PubMed:20861349). They also gained significantly more weight and a greater percentage of body fat than wild-type mice (PubMed:30212649). NLRP12-deficient mice also exhibit enhanced disease in a mouse model of multiple sclerosis (PubMed:26521018). During viral infection, augments host response with greater type I interferon production and RIGI protein (PubMed:30902577).|||Plays an essential role as an potent mitigator of inflammation (PubMed:26521018, PubMed:30559449). Primarily expressed in dendritic cells and macrophages, inhibits both canonical and non-canonical NF-kappa-B and ERK activation pathways (PubMed:30559449). Functions as a negative regulator of NOD2 by targeting it to degradation via the proteasome pathway (PubMed:30559449). In turn, promotes bacterial tolerance (PubMed:30559449). Inhibits also the RIGI-mediated immune signaling against RNA viruses by reducing the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked RIGI activation but enhancing the E3 ubiquitin ligase RNF125-mediated 'Lys-48'-linked RIGI degradation (By similarity). Acts also as a negative regulator of inflammatory response to mitigate obesity and obesity-associated diseases in adipose tissue (PubMed:30212649). http://togogenome.org/gene/10090:Dexi ^@ http://purl.uniprot.org/uniprot/Q9WUQ7 ^@ Similarity ^@ Belongs to the DEXI family. http://togogenome.org/gene/10090:Rpl35 ^@ http://purl.uniprot.org/uniprot/Q6ZWV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL29 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Krtap11-1 ^@ http://purl.uniprot.org/uniprot/E9Q2E9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Zbtb8os ^@ http://purl.uniprot.org/uniprot/B2KGA7|||http://purl.uniprot.org/uniprot/Q505B7 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the archease family.|||Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB. Together with DDX1, acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (By similarity).|||Component of the tRNA-splicing ligase complex.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Tmem219 ^@ http://purl.uniprot.org/uniprot/Q9D123 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell death receptor specific for IGFBP3, may mediate caspase-8-dependent apoptosis upon ligand binding.|||Cell membrane|||Interacts with IGFBP3. Interacts with CASP8 (By similarity). http://togogenome.org/gene/10090:Vgll2 ^@ http://purl.uniprot.org/uniprot/Q8BGW8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the vestigial family.|||Expressed in the somitic myotome from 8.75 dpc mouse embryos onwards and later on in skeletal muscle but not in the heart. Additional expression domains during development are detected in the pharyngeal pouches and clefts starting at 8.0 dpc as well as in the cranial pharynx and in Rathkes pouch.|||Interacts with TEFs. Binds to TEAD1/TEF1.|||May act as a specific coactivator for the mammalian TEFs. May play a role in the development of skeletal muscles.|||Nucleus|||Skeletal muscle specific. http://togogenome.org/gene/10090:Epha10 ^@ http://purl.uniprot.org/uniprot/Q8BYG9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Expressed in the cochlea, in the organ of Corti, spiral ganglion, and stria vascularis.|||Receptor for members of the ephrin-A family. Binds to EFNA3, EFNA4 and EFNA5 (By similarity).|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Cnih1 ^@ http://purl.uniprot.org/uniprot/O35372 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in full grown oocyte and the ovulated unfertilized egg, shows a slight decrease 12 hours after fertilization. Transcripts from the activated embryonic genome are present in the eight-cell embryo.|||Belongs to the cornichon family.|||Endoplasmic reticulum membrane|||Expressed in oocytes, and at a basal level in ovarian somatic cells of 6-week-old mouse. Expressed in adult brain.|||Golgi apparatus membrane|||Interacts with AREG immature precursor and with immature TGFA, i.e. with a prosegment and lacking full N-glycosylation, but not with the fully N-glycosylated form. In the Golgi apparatus, may form a complex with GORASP55 and transmembrane TGFA (By similarity).|||Involved in the selective transport and maturation of TGF-alpha family proteins. http://togogenome.org/gene/10090:Acss3 ^@ http://purl.uniprot.org/uniprot/Q14DH7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (By similarity). Propionate is the preferred substrate but can also utilize acetate and butyrate with a much lower affinity (By similarity).|||Mitochondrion matrix http://togogenome.org/gene/10090:Rbm19 ^@ http://purl.uniprot.org/uniprot/Q8R3C6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Arrests embryonic development prior to implantation. Embryos at 3.5 dpc lack the mature, tripartite nucleoli, but instead, contain spheres resembling nucleolar precursor body (NPB), indicating arrest of nucleologenesis.|||Belongs to the RRM MRD1 family.|||Chromosome|||Cytoplasm|||Expressed during early development. Expressed in the epithelium of the embryonic gut tube (at protein level).|||Expressed in the crypts of Lieberkuhn of the intestine (at protein level).|||Plays a role in embryo pre-implantation development.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Apol7e ^@ http://purl.uniprot.org/uniprot/Q3UZ24 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Llcfc1 ^@ http://purl.uniprot.org/uniprot/Q9D9P8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in testicular germ cells and spermatozoa (at protein level). Abundantly expressed in testis.|||Detected in the testis after postnatal day 28.|||Male infertility (PubMed:32393636). Sperm are morphologically normal, exhibit normal motility and can penetrate the zona pellucida but are unable to fuse with the egg membrane (PubMed:32393636). No effect on amount or localization of sperm-egg fusion protein IZUMO1 (PubMed:32393636).|||Secreted|||Sperm protein required for fusion of sperm with the egg membrane during fertilization. http://togogenome.org/gene/10090:Ly9 ^@ http://purl.uniprot.org/uniprot/Q01965 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with SH2D1A and INPP5D. Interacts (via phosphorylated cytoplasmic domain) with PTPN11; the interaction is blocked by SH2D1A.|||Lymphocytes.|||Membrane|||Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2 (PubMed:19648922). May participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction. Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A. Promotes recruitment of RORC to the IL-17 promoter (By similarity). May be involved in the maintenance of peripheral cell tolerance by serving as a negative regulator of the immune response. May disable autoantibody responses and inhibit IFN-gamma secretion by CD4(+) T-cells (PubMed:23914190). May negatively regulate the size of thymic innate CD8(+) T-cells and the development of invariant natural killer T (iNKT) cells (PubMed:23225888). Can promote natural killer (NK) cell activation (PubMed:19648922).|||The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). http://togogenome.org/gene/10090:Agmat ^@ http://purl.uniprot.org/uniprot/A2AS89 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the arginase family. Agmatinase subfamily.|||Detected only in liver.|||Hydrolyzes linear guanidino acids to form urea and the corresponding amines. Displays specificity for substrates having a negatively charged head group and short chains including taurocyamine, guanidino propanoic and butanoic acids. May protect cells by detoxifying potentially harmful amounts of guanidino acids. Metabolizes L-arginine with low efficiency.|||May have little or no activity due to the lack of several residues essential for manganese binding and catalytic activity.|||Mitochondrion http://togogenome.org/gene/10090:Clec12a ^@ http://purl.uniprot.org/uniprot/A0A0R4J0T2|||http://purl.uniprot.org/uniprot/Q504P2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases.|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases (By similarity).|||Interacts with PTPN6 and PTPN11.|||Membrane http://togogenome.org/gene/10090:Psmg4 ^@ http://purl.uniprot.org/uniprot/P0C7N9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PSMG4 family.|||Chaperone protein which promotes assembly of the 20S proteasome.|||Interacts with PSMG3. Associates with alpha subunits of the 20S proteasome. http://togogenome.org/gene/10090:Tti1 ^@ http://purl.uniprot.org/uniprot/Q91V83 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tti1 family.|||Component of the TTT complex composed of TELO2, TTI1 and TTI2. Interacts with ATM, ATR, MTOR, PRKDC, SMG1, TELO2, TRRAP and TTI2. Component of the mTORC1 and mTORC2 complexes. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation.|||Cytoplasm|||Phosphorylated at Ser-823 by CK2 following growth factor deprivation, leading to its subsequent ubiquitination by the SCF(FBXO9) complex. Phosphorylation by CK2 only takes place when TELO2 is bound to mTORC1, not mTORC2; leading to selective ubiquitination of mTORC1-associated protein (By similarity).|||Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals (By similarity).|||Ubiquitinated by the SCF(FBXO9) complex following phosphorylation by CK2 in response to growth factor deprivation, leading to its degradation by the proteasome. Only mTORC1-associated protein is ubiquitinated and degraded, leading to selective inactivation of mTORC1 to restrain cell growth and protein translation, while mTORC2 is activated due to the relief of feedback inhibition by mTORC1 (By similarity). http://togogenome.org/gene/10090:Fchsd1 ^@ http://purl.uniprot.org/uniprot/Q6PFY1 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell projection|||Cytoplasm|||Cytoplasmic vesicle|||Detected in brain cortex at 15.5 dpc. Highly expressed in brain cortex from young and adult animals (at protein level).|||Detected in inner ear vestibula and in the cuticular plate of cochlear hair cells (at protein level). Ubiquitous. Detected in testis, liver, brain cortex, cerebellum, spiral ganglion and tongue, and at lower levels in the organ of Corti and utricle in the inner ear.|||Homodimer (Probable). Interacts (via F-BAR domain) with SNX9 (via SH3 domain) (PubMed:23437151, PubMed:26567222). Interacts (via F-BAR domain) with SNX18 and SNX33 (PubMed:26567222). Interacts (via SH3 domain 1) with WASL (PubMed:29887380). Interacts (via SH3 domain 2) with ITSN1 (PubMed:29887380).|||Perikaryon|||Promotes actin polymerization mediated by SNX9 and WASL.|||The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes (By similarity). Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions (PubMed:23761074, PubMed:26567222). http://togogenome.org/gene/10090:Vmn2r1 ^@ http://purl.uniprot.org/uniprot/G3X8Y6|||http://purl.uniprot.org/uniprot/O70410 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Expressed at the sensory surface of the vomeronasal organ.|||Membrane|||Putative pheromone receptor.|||The variant protein sequence (Ref.3) is capable of binding the sex pheromone, 2-octanamine (2-1, methyl heptyl) via aa 11-17. http://togogenome.org/gene/10090:Krtap14 ^@ http://purl.uniprot.org/uniprot/O08640 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PMG family.|||Expressed at high levels in skin where it is found predominantly in the keratogenous zone of hair follicle cortical cells and at lower levels in the epithelium of the developing mammary gland.|||In the developing mammary gland, expression is barely detected in the immature gland at 3 weeks after birth but is evident at the onset of puberty at 3.5 weeks. Expression is high at 4 weeks, declines at 4.5 weeks and is undetectable at 5 weeks. No expression is detected in the mature mammary gland during estrus, pregnancy, lactation or involution. In skin, expression starts shortly after birth and reaches a first maximum at 9 days. A second peak of expression is observed at 3.5 weeks, then levels decline and remain low in the adult. During the hair growth cycle, detected in mid- and late-anagen stages but not in catagen, telogen or early anagen phases.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Gmps ^@ http://purl.uniprot.org/uniprot/Q3THK7 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the conversion of xanthine monophosphate (XMP) to GMP in the presence of glutamine and ATP through an adenyl-XMP intermediate.|||Homodimer.|||Stimulated by dithiothreitol and inhibited by 2-mercaptoethanol, p-chloromercuribenzoate and hydroxylamine.|||cytosol http://togogenome.org/gene/10090:Pgm5 ^@ http://purl.uniprot.org/uniprot/Q8BZF8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphohexose mutase family.|||Component of adherens-type cell-cell and cell-matrix junctions. Has no phosphoglucomutase activity in vitro.|||Interacts with DMD/dystrophin; the interaction is direct (PubMed:7890770). Interacts with UTRN/utrophin (By similarity).|||adherens junction|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Plin1 ^@ http://purl.uniprot.org/uniprot/Q8CGN5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the perilipin family.|||Endoplasmic reticulum|||Interacts with ABHD5 (PubMed:15292255). Interacts with CIDEC (PubMed:23481402). Interacts with AQP7 (By similarity).|||Lipid droplet|||Major cAMP-dependent protein kinase-substrate in adipocytes, also dephosphorylated by PP1. When phosphorylated, may be maximally sensitive to HSL and when unphosphorylated, may play a role in the inhibition of lipolysis, by acting as a barrier in lipid droplet (By similarity).|||Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness (By similarity). Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels. http://togogenome.org/gene/10090:Or10w1 ^@ http://purl.uniprot.org/uniprot/Q7TQQ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sult1c1 ^@ http://purl.uniprot.org/uniprot/Q80VR3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Cytoplasm|||Expressed only in olfactory tissue. Detected in sustentacular cells in the dorso-medial portion of the nasal cavity.|||Inhibited by 2,6-dichloro-4-nitrophenol but not by triethylamine or tetra-n-butyl-ammonium chloride.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of drugs, xenobiotic compounds, hormones, and neurotransmitters. May be involved in the activation of carcinogenic hydroxylamines. Shows activity towards p-nitrophenol and N-hydroxy-2-acetylamino-fluorene (N-OH-2AAF). Also shows activity towards cinnamyl alcohol at pH 6.4 but not at pH 5.5, and towards a number of phenolic odorants including eugenol, guaiacol and 2-naphthol. http://togogenome.org/gene/10090:Cyth4 ^@ http://purl.uniprot.org/uniprot/Q80YW0 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Autoinhibited by its C-terminal basic region.|||Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate.|||Cell membrane|||Promotes guanine-nucleotide exchange on ARF1 and ARF5. Promotes the activation of ARF factors through replacement of GDP with GTP (By similarity). http://togogenome.org/gene/10090:Pyurf ^@ http://purl.uniprot.org/uniprot/Q9D1C3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PREY family.|||In mitochondria, S-adenosylmethionine-dependent methyltransferase chaperone that supports both coenzyme Q biosynthesis, by stabilizing its components, such as COQ5, and NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) assembly, by stabilizing complex I assembly factors, such as NDUFAF5.|||Interacts (via TRM112 domain) with NDUFAF5; the interaction is direct and stabilizes NDUFAF5 protein. Interacts with COQ5; the interaction is direct, stabilizes COQ5 protein and associates PYURF with COQ enzyme complex.|||Mitochondrion http://togogenome.org/gene/10090:Zc3h13 ^@ http://purl.uniprot.org/uniprot/E9Q784 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29535189, PubMed:29547716). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (PubMed:29547716). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (PubMed:29547716). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (PubMed:29547716). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (PubMed:29535189).|||Belongs to the ZC3H13 family.|||Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, RBM15, BCLAF1 and THRAP3 (By similarity).|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Luzp1 ^@ http://purl.uniprot.org/uniprot/Q8R4U7 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Predominantly expressed in the brain (at protein level).|||centrosome http://togogenome.org/gene/10090:Nkd1 ^@ http://purl.uniprot.org/uniprot/E9Q5K6|||http://purl.uniprot.org/uniprot/Q99MH6 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKD family.|||Cell autonomous antagonist of the canonical Wnt signaling pathway.|||Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity. Required for spermatogenesis.|||Cell membrane|||Cytoplasm|||Expressed throughout embryonic development. Expressed in the presomitic mesoderm (PSM) and the neural folds along the entire rostrocaudal axis at 8.5 days post-coitum (dpc). Expressed in the forelimb buds, the branchial arches, and at the anterior and posterior of each somite boundary at 9.5 dpc. Expressed in the neural tube, the PSM, somites and the dorsal limb bud mesenchyme at 10.5 dpc. At 11.5 dpc three distinct phases of expression can be seen; expression is initially low in the tailbud, rises in the PSM and then shifts anteriorly. These oscillations require the activity of HES7.|||Expression is induced by activation of the Wnt signaling pathway.|||Highly expressed in lung. Also expressed in brain, heart, kidney, liver, skin, stomach and testis. Within the testis expression is found in the seminiferous epithelium and round and elongating spermatids.|||Interacts with DVL1, DVL2, DVL3 and PPP2R3A. http://togogenome.org/gene/10090:Fam131a ^@ http://purl.uniprot.org/uniprot/D3Z4E4|||http://purl.uniprot.org/uniprot/Q8BWU3 ^@ Similarity ^@ Belongs to the FAM131 family. http://togogenome.org/gene/10090:Tfip11 ^@ http://purl.uniprot.org/uniprot/Q3TTV6|||http://purl.uniprot.org/uniprot/Q9ERA6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TFP11/STIP family.|||Cytoplasm|||Expressed as early as 14 dpc and continues into postnatal development. Within the developing tooth, expression is localized at the apical region of the ameloblast cells and to the apical regions of the newly formed enamel matrix.|||Identified in the spliceosome C complex. Found in the Intron Large (IL) complex, a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors. Interacts with TUFT1. Interacts with DHX15; indicative for a recruitment of DHX15 to the IL complex. Interacts with GCFC2.|||Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events. Intron turnover seems to proceed through reactions in two lariat-intron associated complexes termed Intron Large (IL) and Intron Small (IS). In cooperation with DHX15 seems to mediate the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns. May play a role in the differentiation of ameloblasts and odontoblasts or in the forming of the enamel extracellular matrix.|||Nucleus|||Widely expressed. In tooth it is expressed in ameloblasts and odontoblasts. http://togogenome.org/gene/10090:Irak4 ^@ http://purl.uniprot.org/uniprot/Q8R4K2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome (PubMed:16951688). Once phosphorylated, IRAK4 dissociates from the receptor complex and then associates with the TNF receptor-associated factor 6 (TRAF6), IRAK1, and PELI1; this intermediate complex is required for subsequent NF-kappa-B activation (PubMed:16951688). Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression (By similarity). Interacts with IL1RL1 (By similarity). Interacts (when phosphorylated) with IRAK1 (By similarity). May interact (when phosphorylated) with IRAK3 (By similarity).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.|||Cytoplasm|||Mice are strongly altered in their responses to viral and bacterial challenges due to a severe impairment of interleukin-1 and Toll-like receptor signaling pathways. Malt1 and Irak4 double knockout suggests an additional role of Irak4 in B-cell antigen receptor (BCR) mediated signaling pathway, since the double mutant inhibits B-cell proliferation.|||Phosphorylated.|||Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections (By similarity). http://togogenome.org/gene/10090:Pcbp3 ^@ http://purl.uniprot.org/uniprot/P57722 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||May be due to a competing acceptor splice site.|||Single-stranded nucleic acid binding protein that binds preferentially to oligo dC.|||Widely expressed, with highest levels in testis and fat tissues and lowest in heart. http://togogenome.org/gene/10090:Armcx4 ^@ http://purl.uniprot.org/uniprot/E9PWM3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the eutherian X-chromosome-specific Armcx family.|||Membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Serpind1 ^@ http://purl.uniprot.org/uniprot/P49182 ^@ Domain|||Function|||PTM|||Similarity|||Tissue Specificity ^@ Belongs to the serpin family.|||Expressed predominantly in liver.|||N-glycosylated; different glycan composition appears to lead to two forms of this protein (68 and 72 kDa).|||The N-terminal acidic repeat region mediates, in part, the glycosaminoglycan-accelerated thrombin inhibition.|||Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT). Also inhibits chymotrypsin, but in a glycosaminoglycan-independent manner. http://togogenome.org/gene/10090:Or4c3d ^@ http://purl.uniprot.org/uniprot/Q60878 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Zfp322a ^@ http://purl.uniprot.org/uniprot/Q8BZ89 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Expressed in the inner cell mass of the blastocyst during preimplantation stage embryonic development.|||Interacts with POU5F1.|||Nucleus|||Significantly enhances POU5F1/OCT4-SOX2-KLF4-MYC (OSKM) mediated reprogramming of mouse embryonic fibroblasts into induced pluripotent stem cells, and can also substitute for SOX2 in this process.|||Transcriptional activator. Important for maintenance of pluripotency in embryonic stem cells. Binds directly to the POU5F1 distal enhancer and the NANOG proximal promoter, and enhances expression of both genes. Can also bind to numerous other gene promoters and regulates expression of many other pluripotency factors, either directly or indirectly. Promotes inhibition of MAPK signaling during embryonic stem cell differentiation. http://togogenome.org/gene/10090:Hipk4 ^@ http://purl.uniprot.org/uniprot/Q3V016 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.|||Cytoplasm|||Expressed at moderate levels in lung and white adipose tissues and weakly in brain and liver.|||Protein kinase that phosphorylates murine TP53 at Ser-9, and thus induces TP53 repression of BIRC5 promoter. May act as a corepressor of transcription factors (Potential). http://togogenome.org/gene/10090:Defa30 ^@ http://purl.uniprot.org/uniprot/E9QPZ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Atg13 ^@ http://purl.uniprot.org/uniprot/Q91YI1 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.|||Belongs to the ATG13 family. Metazoan subfamily.|||Part of a complex consisting of ATG13, ULK1 and RB1CC1 (PubMed:19258318, PubMed:19211835). Interacts with ATG101 (By similarity). Interacts with ULK1 (via C-terminus); this interaction is increased in the absence of TMEM39A (By similarity). Interacts with ULK2 (via C-terminus) (By similarity). Interacts (via the LIR motif) with GABARAP, GABARAPL and GABARAPL2 (By similarity). Interacts (via the LIR motif) with MAP1LC3A, MAP1LC3B and MAP1LC3C (By similarity). Interacts with TAB2 and TAB3 (By similarity). Interacts with C9orf72 (By similarity). Interacts with RB1CC1; this interaction is increased in the absence of TMEM39A (By similarity).|||Phosphorylated by ULK1, ULK2 and mTOR. Phosphorylation status depends on nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. ULK1-mediated phosphorylation of ATG13 at Ser-354 is required for efficient clearance of depolarized mitochondria.|||Preautophagosomal structure|||The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and MAP1LC3A.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||cytosol http://togogenome.org/gene/10090:Cfap210 ^@ http://purl.uniprot.org/uniprot/A0JLY1 ^@ Function|||Subcellular Location Annotation ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Klhl36 ^@ http://purl.uniprot.org/uniprot/Q8R124 ^@ Function|||Subunit ^@ Interacts with CUL3.|||Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. http://togogenome.org/gene/10090:Mapk9 ^@ http://purl.uniprot.org/uniprot/Q5NCK8|||http://purl.uniprot.org/uniprot/Q8C094|||http://purl.uniprot.org/uniprot/Q9WTU6 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by threonine and tyrosine phosphorylation by either of two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual specificity phosphatases, such as DUSP1.|||All four isoforms are widely distributed in brain. Isoforms alpha-1 and alpha-2 are predominantly expressed in hippocampus, cerebral cortex, caudate-putamen, amygdala and the granule layer of the cerebellum. Alpha-1 is more abundant than alpha-2 in the periaqueductal region and the substantia nigra.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Cytoplasm|||Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and MAP2K4, which activates the enzyme. Autophosphorylated in vitro.|||In T-cells, following T-cell receptor (TCR) activation. Levels peak 48 hours after TCR and CD-28 costimulation.|||Interacts with MECOM (By similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway (PubMed:11562351). Interacts with NFATC4 (By similarity). Interacts with ATF7; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN (By similarity). Interacts with BCL10 (By similarity). Interacts with CTNNB1 and GSK3B (By similarity). Interacts with DCLK2 (PubMed:16628014). Interacts with MAPKBP1 (By similarity). Interacts with POU5F1; phosphorylates POU5F1 at 'Ser-347' (PubMed:29153991). Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:27084103).|||Nucleus|||Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.|||Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3. Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption. When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (PubMed:29153991).|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. http://togogenome.org/gene/10090:Cck ^@ http://purl.uniprot.org/uniprot/P09240 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gastrin/cholecystokinin family.|||Binds to CCK-A receptors in the pancreas and CCK-B receptors in the brain.|||Expressed and secreted by discrete enteroendocrine cells that reside as single cells scattered among enterocytes in the mucosa of the small intestine. Released into the blood following ingestion of a meal.|||Secreted|||The precursor is cleaved by proteases to produce a number of active cholecystokinins.|||This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear. Binding to CCK-A receptors stimulates amylase release from the pancreas, binding to CCK-B receptors stimulates gastric acid secretion. http://togogenome.org/gene/10090:Nuf2 ^@ http://purl.uniprot.org/uniprot/Q99P69 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules.|||Belongs to the NUF2 family.|||Can be phosphorylated by AURKA and AURKB.|||Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end. May interact with AURKB/Aurora-B (By similarity).|||Nucleus|||kinetochore http://togogenome.org/gene/10090:Fgf16 ^@ http://purl.uniprot.org/uniprot/A0A7U3JW97|||http://purl.uniprot.org/uniprot/Q9ESL8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Interacts with FGFR1 and FGFR2.|||Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation, and is required for normal cardiomyocyte proliferation and heart development.|||Secreted http://togogenome.org/gene/10090:Vmn2r68 ^@ http://purl.uniprot.org/uniprot/L7N2B3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cops2 ^@ http://purl.uniprot.org/uniprot/P61202 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CSN2 family.|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS1, COPS4, COPS5, COPS6 and COPS7 (COPS7A or COPS7B) (PubMed:9707402). Specifically interacts with the ligand binding domain of the thyroid receptor (TR). Does not require the presence of thyroid hormone for its interaction. Interacts with CUL1 and CUL2 (PubMed:11967155). Interacts with IRF8/ICSBP1 and with nuclear receptors NR2F1 and NR0B1 (By similarity). Interacts with NIF3L1 (PubMed:12522100).|||Cytoplasm|||Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Involved in early stage of neuronal differentiation via its interaction with NIF3L1.|||Its absence causes arrest of embryo development at the peri-implantation stage. Blastocysts without Cops2 fail to outgrow in culture and exhibit a cell proliferation defect in inner cell mass, accompanied by a slight decrease in Oct4. In addition, lack of Cops2 disrupts the CSN complex and results in a drastic increase in cyclin E. It also induces elevated levels of p53 and p21, which may contribute to premature cell cycle arrest of the mutant.|||Nucleus|||Phosphorylated by CK2 and PKD kinases.|||Widely expressed in embryonic, fetal and adult tissues, except cartilage and smooth muscle. http://togogenome.org/gene/10090:Atrip ^@ http://purl.uniprot.org/uniprot/Q8BMG1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATRIP family.|||Heterodimer with ATR. The heterodimer binds the RPA complex and is then recruited to single-stranded DNA. Interacts with CINP (By similarity). Interacts with ATR.|||Nucleus|||Phosphorylated by ATR.|||Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein (By similarity).|||The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage. http://togogenome.org/gene/10090:S100a14 ^@ http://purl.uniprot.org/uniprot/Q9D2Q8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the S-100 family.|||Cytoplasm|||Homodimer. Interacts with AGER (By similarity).|||Modulates P53/TP53 protein levels, and thereby plays a role in the regulation of cell survival and apoptosis. Depending on the context, it can promote cell proliferation or apoptosis. Plays a role in the regulation of cell migration by modulating the levels of MMP2, a matrix protease that is under transcriptional control of P53/TP53. Does not bind calcium (By similarity). http://togogenome.org/gene/10090:Zfp951 ^@ http://purl.uniprot.org/uniprot/Q3V1G7 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Msh5 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZY8|||http://purl.uniprot.org/uniprot/Q9QUM7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DNA mismatch repair MutS family.|||Heterooligomer of MSH4 and MSH5. Interacts with HJURP (By similarity).|||Involved in DNA mismatch repair and meiotic recombination processes. Facilitates crossovers between homologs during meiosis (By similarity). http://togogenome.org/gene/10090:Zdhhc12 ^@ http://purl.uniprot.org/uniprot/Q8VC90 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DHHC palmitoyltransferase family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Mice display enhanced inflammatory symptoms and lethality following alum-induced peritonitis and LPS-induced endotoxic shock; defects are caused by an increased NLRP3 inflammasome activation.|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates (PubMed:25025157). Has a palmitoyltransferase activity toward gephyrin/GPHN, regulating its clustering at synapses and its function in gamma-aminobutyric acid receptor clustering (PubMed:25025157). Thereby, indirectly regulates GABAergic synaptic transmission (PubMed:25025157). Acts as an inhibitor of the NLRP3 inflammasome by mediating palmitoylation of NLRP3, thereby promoting NLRP3 degradation by the chaperone-mediated autophagy (CMA) process (PubMed:36586411).|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Mapk8ip3 ^@ http://purl.uniprot.org/uniprot/E9Q6B6|||http://purl.uniprot.org/uniprot/E9Q6E0|||http://purl.uniprot.org/uniprot/Q3UHB5|||http://purl.uniprot.org/uniprot/Q6P1F1|||http://purl.uniprot.org/uniprot/Q9ESN9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JIP scaffold family.|||Cytoplasm|||Cytoplasmic vesicle|||Expressed in neurites 5 days following initiation of nerve growth factor induced differentiation. NGF withdrawal results in the down-regulation of MAPK8IP3 protein by caspase-mediated cleavage.|||Forms homo- or heterooligomeric complexes. The central region of MAPK8IP3 interacts with the C-terminal of MAPK8IP2 but not MAPK8IP1. Binds specific components of the JNK signaling pathway namely MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 to the N-terminal region, MAP2K4/MKK4 and MAP2K7/MKK7 to the central region and MAP3K11 to the C-terminal region. Binds the TPR motif-containing C-terminal of kinesin light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location (PubMed:10523642, PubMed:10629060, PubMed:11238452, PubMed:11106729). Interacts with ROCK1 and this interaction is enhanced by ultraviolet-B (UVB) radiation. Interacts with SH3RF2 (By similarity). Interacts with NTRK2/TRKB and NTRK3/TRKC (PubMed:21775604).|||Golgi apparatus|||Highly expressed in the brain of embryonic mice. Expression levels gradually increase from 10 dpc to postnatal day 10 (P10) (at protein level).|||Highly expressed throughout many regions of the brain and at lower levels in the heart, liver, lung, testes and kidney. All isoforms have been identified in the brain, isoform 1a is also expressed in the spleen and lung.|||Phosphorylation by ROCK1 is crucial for the recruitment of JNK.|||The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (PubMed:10523642, PubMed:10629060). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner (PubMed:23576431, PubMed:25944905, PubMed:28259553). Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation (PubMed:23576431, PubMed:25944905, PubMed:28259553). Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration (PubMed:23576431, PubMed:25944905, PubMed:28259553). Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (PubMed:23576431, PubMed:25944905, PubMed:28259553). Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:23576431, PubMed:25944905, PubMed:28259553).|||The cerebral cortex in the embryonic brain is a little thinner and the distribution of neurons is more disordered than that found in the wild-type littermates.|||axon|||dendrite|||growth cone|||perinuclear region http://togogenome.org/gene/10090:Tnnt1 ^@ http://purl.uniprot.org/uniprot/O88346|||http://purl.uniprot.org/uniprot/Q3TVB8 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the troponin T family.|||Expressed in adult soleus muscle.|||In masseter expression decreases during development and becomes undetectable 3 weeks after birth.|||Major.|||Minor.|||Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. http://togogenome.org/gene/10090:Or9m1 ^@ http://purl.uniprot.org/uniprot/L7MU57 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prtn3 ^@ http://purl.uniprot.org/uniprot/Q61096 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S1 family. Elastase subfamily.|||Cell membrane|||Lysosome|||May form dimers. Interacts with CD177; the interaction tethers PRTN3 to the cell surface; the interaction is direct. Interacts with SERPINB1.|||Membrane raft|||Secreted|||Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration. May play a role in neutrophil transendothelial migration, probably when associated with CD177. http://togogenome.org/gene/10090:Myo10 ^@ http://purl.uniprot.org/uniprot/F8VQB6 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Detected in brain, heart, kidney, liver, stomach, skeletal muscle, lung, testis and skin. Isoform Headless is expressed in embryonic and neuronal stem cells, and enriched in proliferating and migrating cells.|||Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion.|||IQ 3 domain mediates high-affinity calcium-dependent binding to CALM3/CLP.|||Interaction between the motor domain and the tail leads to an inactive, monomeric conformation. Phospholipid binding via the PH domains leads to the formation of the active, dimeric form of the protein and strongly increases actin-dependent ATPase activity and motor activity (By similarity).|||Interacts with membranes containing phosphatidylinositol-3,4,5-trisphosphate via the PH domains.|||Monomer, when in an inactive conformation in the cytosol. Homodimer in its active, membrane-bound conformation; antiparallel coiled coil-mediated dimer formation. Interacts with ECPAS. Interacts with DCC and ITGB5; the presence of DCC inhibits ITGB5 binding. Interacts with tubulin; ITGB5 or DCC binding inhibits tubulin binding. Interacts strongly with CALM3 and weakly with CALM, the CALM3 interaction is essential for function in filopodial extension and motility. Interacts with ITGB1, ITGB3 and ITGB5 (By similarity). Interacts with NEO1. Interacts with VASP.|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as a plus end-directed motor. Moves with higher velocity and takes larger steps on actin bundles than on single actin filaments (By similarity). The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments (By similarity). Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts.|||Produced by alternative promoter usage.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-10 (MYH10).|||The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (PubMed:16030012). It can refold after extension suggesting an in vivo force-dependent function (By similarity). An anti-parallel coiled coil is located C-terminal to the SAH domain and mediates dimerization (By similarity).|||The initiator methionine for isoform Headless is removed.|||cell cortex|||cytoskeleton|||cytosol|||filopodium membrane|||filopodium tip|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Vmn2r52 ^@ http://purl.uniprot.org/uniprot/L7N2B2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrpl46 ^@ http://purl.uniprot.org/uniprot/Q9EQI8 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL46 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Gcdh ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ68|||http://purl.uniprot.org/uniprot/Q60759|||http://purl.uniprot.org/uniprot/Q8BVD4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Animals show highly increased protein glutarylation in liver.|||Belongs to the acyl-CoA dehydrogenase family.|||Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor.|||Homotetramer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Ccno ^@ http://purl.uniprot.org/uniprot/B2RWG0|||http://purl.uniprot.org/uniprot/P0C242 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cyclin family.|||Cytoplasm|||Expressed in ependymal cells of the embryonic brain, but almost absent in the adult brain.|||Present in respiratory cells (at protein level). Expressed in multiciliated tissue in brain and fallopian tube (at protein level) (PubMed:26777464). Highly expressed in oocytes.|||Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation. Acts downstream of MCIDAS to promote mother centriole amplification and maturation in preparation for apical docking (By similarity). May be involved in apoptosis in lymphoid cells; however, this result requires additional evidences in vivo. May be involved in oocyte meiotic resumption in oocytes.|||nucleolus http://togogenome.org/gene/10090:Cntrob ^@ http://purl.uniprot.org/uniprot/Q8CB62 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with LYST.|||Required for centriole duplication. Inhibition of centriole duplication leading to defects in cytokinesis (By similarity).|||centriole http://togogenome.org/gene/10090:Nlk ^@ http://purl.uniprot.org/uniprot/O54949 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by the non-canonical Wnt signaling pathway, in which WNT5A leads to activation of MAP3K7/TAK1 and HIPK2, which subsequently phosphorylates and activates this protein. Activated by dimerization and subsequent intermolecular autophosphorylation on Thr-298. Other cytokines such as IL6 may also activate this regulatory circuit.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-298) is sufficient for kinase activation. This mode of activation contrasts with that of classical MAP kinases, which contain a TXY activation loop motif in which phosphorylation of both the threonine and tyrosine residues is required for kinase activation.|||Cytoplasm|||Expressed at high levels in the brain, and at lower levels in heart, kidney, lung and liver.|||Homodimer. Homodimerization is required for intermolecular autophosphorylation, kinase activation and nuclear localization (PubMed:21118996). Interacts with RNF138/NARF (By similarity). Interacts with FOXO1 and FOXO3 (By similarity). Interacts with the upstream activating kinases HIPK2 and MAP3K7/TAK1. Interaction with MAP3K7/TAK1 seems to be indirect, and may be mediated by other proteins such as STAT3, TAB1 and TAB2. Interacts with and phosphorylates a number of transcription factors including FOXO4, LEF1, MYB, MYBL1, MYBL2, NOTCH1 and TCF7L2/TCF4. May interact with components of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. Interacts with MEF2A (PubMed:12556497, PubMed:15004007, PubMed:15082531, PubMed:15308626, PubMed:16055500, PubMed:17785444, PubMed:18765672, PubMed:20118921, PubMed:20194509, PubMed:20874444). Interacts with ATF5; the interaction stabilizes ATF5 at the protein level in a kinase-independent manner (By similarity).|||Nucleus|||Phosphorylated on Thr-298. Intermolecular autophosphorylation on Thr-298 activates the enzyme.|||Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:10391247, PubMed:11745377, PubMed:12482967, PubMed:12556497, PubMed:14720327, PubMed:15004007, PubMed:17785444, PubMed:18765672, PubMed:20874444, PubMed:21118996, PubMed:9448268). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:20194509). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:12556497). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12556497). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:16055500). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531, PubMed:15308626, PubMed:16055500). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531, PubMed:15308626, PubMed:16055500). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (By similarity). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (By similarity). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (By similarity). http://togogenome.org/gene/10090:Pramel40 ^@ http://purl.uniprot.org/uniprot/L7N456 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Vmn1r226 ^@ http://purl.uniprot.org/uniprot/Q8R2A8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tsr3 ^@ http://purl.uniprot.org/uniprot/Q5HZH2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA. It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA.|||Belongs to the TDD superfamily. TSR3 family.|||Cytoplasm http://togogenome.org/gene/10090:Kcna2 ^@ http://purl.uniprot.org/uniprot/P63141 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily.|||Cell membrane|||Detected at low levels in brainstem from neonates; increases tenfold during the first 29 days after birth.|||Detected in brain (PubMed:17634333). Detected in cerebellum (PubMed:20696761). Detected in mitral cells in the olfactory bulb (PubMed:8046438). Detected in cochlea (PubMed:23864368). Detected in cerebellum, particularly in the basket cell axon plexus and in the terminal regions around Purkinje cells (at protein level) (PubMed:8361541, PubMed:8046438, PubMed:18760366, PubMed:26269648). Detected in juxtaparanodal regions in sciatic nerve (PubMed:22649228). Detected in Schwann cells from sciatic nerve (PubMed:9852577). Detected in dopamine neurons in substantia nigra (PubMed:21233214). Detected in large myelinated fibers in juxtaparanodes in the CA3 and CA1 areas of the hippocampus (PubMed:8046438, PubMed:18760366). Detected in brain, in punctae on fiber tracts in brain stem and spinal cord, and on axons in the juxtaparanodal regions of the node of Ranvier (at protein level) (PubMed:8361541). Detected in dopamine neurons in the midbrain (PubMed:21233214).|||Endoplasmic reticulum membrane|||Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8361541, PubMed:9852577, PubMed:23864368). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (By similarity). Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts with PTK2B (By similarity). Interacts (via C-terminus) with CTTN (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (PubMed:9635436). Interacts with DRD2 (PubMed:21233214). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (PubMed:23332758). Interacts with ADAM11 (PubMed:26269648).|||Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (PubMed:12527813). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity).|||Membrane|||Mutagenesis with N-ethyl-N-nitrosourea (ENU) lead to the discovery of the Pingu (Pgu) phenotype. At P21, heterozygous mice are clearly smaller than wild-type and have abnormal gait with a higher stance and splayed hind limbs. Homozygous mice are even smaller, and about half of them die between P15 and P35. Mutant mice have difficulty staing on a rotating rod and perform poorly in a beam-walking test, where they display flattened posture, severe tremors, myoclonic jerks and ataxic movement. These symptoms are alleviated by a drug used to treat cerebellar ataxia. Measurements with Purkinje cells from cerebellar brain slices show increased frequency and amplitude of spontaneous inhibitory postsynaptic currents.|||N-glycosylated, with complex, sialylated N-glycans.|||Perikaryon|||Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (By similarity). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (By similarity). Phosphorylation on tyrosine residues suppresses ion channel activity (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN. This is probably due to endocytosis of the phosphorylated channel subunits (By similarity). Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (By similarity).|||Presynaptic cell membrane|||Pups are born at the expected Mendelian rate and appear normal during the first 14 days after birth. Starting at 14 to 17 days after birth, mice exhibit susceptibility to generalized seizures, followed by full tonic extension, which in mice often results in fatal apne. The average lifespan is 17 days; none survive more than 28 days (PubMed:17925011, PubMed:17634333). At P17 seizures are very rare and abnormal electroencephalograph activity is only present during the seizure. P17 pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than wild-type siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes (PubMed:17925011). Auditory neurons from the medial nucleus of the trapezoid body in brain stem are hypoexcitable and fire fewer action potentials than wild-type neurons with significantly smaller threshold current amplitudes (PubMed:17634333). In the inner ear, spiral ganglion neurons display a hyperpolarized resting membrane potential, increased excitability and increased outward potassium currents; this might be because normally channels there are heterotetramers formed by KCNA2 and KCNA4, so the loss of KCNA2 changes channel characteristics (PubMed:23864368).|||Synapse|||The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (By similarity). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (By similarity).|||The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:12527813, PubMed:21233214). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20696761). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:23864368). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:23864368). Contributes to the regulation of action potentials in neurons (PubMed:12527813, PubMed:17925011). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:17634333, PubMed:17925011). Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). KCNA2-containing channels play a role in GABAergic transmission from basket cells to Purkinje cells in the cerebellum, and thereby play an import role in motor coordination (PubMed:20696761). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (PubMed:23981714). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21233214). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (PubMed:17925011).|||axon|||dendrite|||lamellipodium membrane|||paranodal septate junction|||synaptosome http://togogenome.org/gene/10090:Ajuba ^@ http://purl.uniprot.org/uniprot/Q91XC0 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Ajuba' means 'curiosity' in Urdu, an Indian dialect.|||Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1.|||Belongs to the zyxin/ajuba family.|||Cell junction|||Cell membrane|||Detected in all embryonic germ layers, in the extraembryonic yolk sac blood islands and in the fetal components of the developing placenta. As development progressed, expression is dramatically restricted.|||Expressed in skin, brain and genitourinary organs.|||Interacts with SLC1A2. Interacts with AURKA; the interaction occurs during mitosis and both proteins are phosphorylated as they form a complex. Interacts with CTNNA1 and with F-actin. Interacts with LATS2; the interaction occurs during mitosis and the complex regulates organization of the spindle apparatus through recruitment of TUBG to the centrosome. Forms a complex with SQSTM1, PRKCZ and TRAF6. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly (via the LIM domains) with GFI1; the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes, and is independent of the GFI1 SNAG domain. Interacts with HDAC1, HDAC2 and HDAC3 (By similarity). Interacts with GRB2 and PIP5K1B. Interacts with HDAC1, HDAC2 and HDAC3. Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM domains) with VHL (By similarity). Interacts (via LIM domains) with SNAI1 (via SNAG domain), SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain).|||LIM region interacts with CTNNA1. The preLIM region binds directly actin filaments (By similarity).|||LIM-2 and LIM-3 domains mediate the interaction with the N-terminal region of AURKA. The association between LATS2 and AJUBA required the second LIM domain of AJUBA (By similarity).|||Nucleus|||P-body|||Phosphorylated by LATS2 during mitosis. Phosphorylated by AURKA (By similarity).|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Spindoc ^@ http://purl.uniprot.org/uniprot/Q05AH6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Interacts with SPIN1, SPIN2A, SPIN2B, SPIN3 and SPIN4. Interacts with TCF7L2 in a SPIN1-dependent manner. Interacts with PARP1; promoting PARP1 ADP-ribosyltransferase activity.|||Mice were born at the expected Mendelian rate and are viable (PubMed:34737271). Mice are however slightly smaller and display reduced levels of poly-ADP-ribosylation (PubMed:34737271). Moreover, they are hypersensitive to ionizing radiation-induced DNA damage (PubMed:34737271).|||Negatively regulates the transcriptional activator activity of SPIN1 via inhibition of its histone methyl-binding ability (PubMed:29061846). Represses the expression of a number of SPIN1-regulated genes and the SPIN1-mediated activation of the Wnt signaling pathway (PubMed:29061846). Can also inhibit the histone methyl-binding abilities of SPIN2A, SPIN2B, SPIN3 and SPIN4 (By similarity). Positively regulates poly-ADP-ribosylation in response to DNA damage; acts by facilitating PARP1 ADP-ribosyltransferase activity (PubMed:34737271).|||Nucleus http://togogenome.org/gene/10090:F2rl2 ^@ http://purl.uniprot.org/uniprot/O08675 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.|||Interacts with INSC/inscuteable and GPSM2. http://togogenome.org/gene/10090:Snd1 ^@ http://purl.uniprot.org/uniprot/Q78PY7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (By similarity). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition (By similarity). Functions as a bridging factor between STAT6 and the basal transcription factor (By similarity). Plays a role in PIM1 regulation of MYB activity (By similarity). Functions as a transcriptional coactivator for STAT5 (PubMed:12819296).|||Forms a ternary complex with STAT6 and POLR2A (By similarity). Associates with the RNA-induced silencing complex (RISC) (PubMed:24882364). Interacts with the RISC components AGO2, FMR1 and TNRC6A. Interacts with GTF2E1 and GTF2E2 (By similarity). Interacts with PIM1 (By similarity). Interacts with STAT5 (PubMed:12819296). Interacts with SYT11 (via C2 2 domain); the interaction with SYT11 is direct (PubMed:24882364).|||Melanosome|||Nucleus|||Phosphorylated by PIM1 in vitro. http://togogenome.org/gene/10090:Fas ^@ http://purl.uniprot.org/uniprot/P25446 ^@ Disease Annotation|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DAXX (PubMed:9215629). Interacts with HIPK3 (PubMed:11034606). Part of a complex containing HIPK3 and FADD (By similarity). Binds RIPK1 and FAIM2. Interacts with BABAM2 and FEM1B. Interacts with FADD (By similarity). Interacts directly (via DED domain) with NOL3 (via CARD domain); inhibits death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (PubMed:15383280). Interacts with CALM (By similarity). In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage (By similarity).|||Cell membrane|||Contains a death domain involved in the binding of FADD, and maybe to other cytosolic adapter proteins.|||Defects in Fas are the cause of the lymphoproliferation phenotype (lpr) (PubMed:1372394). Lpr mice show lymphadenopathy and autoantibody production (PubMed:1372394).|||Detected in various tissues including thymus, liver, lung, heart, and adult ovary.|||Expression oscillates in a circadian manner in the liver with peak levels seen at CT12.|||Membrane raft|||Palmitoylated. Palmitoylation by ZDHHC7 prevents the lysosomal degradation of FAS regulating its expression at the plasma membrane.|||Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both (By similarity). http://togogenome.org/gene/10090:Vmn2r26 ^@ http://purl.uniprot.org/uniprot/Q6TAC4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Expressed in the basal epithelium of the vomeronasal organ. Located to vomeronasal sensory neurons that project their axons to six to ten glomeruli that reside in globally conserved areas within the caudal accessory olfactory bulb (AOB).|||Putative pheromone receptor. http://togogenome.org/gene/10090:Abcc4 ^@ http://purl.uniprot.org/uniprot/E9Q236|||http://purl.uniprot.org/uniprot/E9Q467 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins. Mediates also the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4). The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4. Mediates the cotransport of bile acids with reduced glutathione (GSH). Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules (Probable). Confers resistance to anticancer agents (Probable).|||Apical cell membrane|||Basolateral cell membrane|||Homozygous null mice are viable and fertile and exhibit any overt phenotype under normal conditions. However deficient mice show impaired anion transport in the blood-brain and blood-cerebrospinal fluid barriers and kidney. Deficient mice show an accumulation of the anticancer agent topotecan in brain and cerebrospinal fluid (CSF) (PubMed:15314169). In addition, penetration of PMEA, an antiviral agent, into the brain is increased in deficient mice (PubMed:17210706).|||Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); this interaction accelerates MRP4 internalization.|||Membrane|||N-glycosylated; leading to substrate-selective effects on its transport activity.|||Ubiquitously expressed across all developmental stages. http://togogenome.org/gene/10090:Selenon ^@ http://purl.uniprot.org/uniprot/D3Z2R5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with RYR1, RYR2 and RYR3.|||Mutant mice show only subtle alterations in the muscle morphology, ultrastructure and contractility. They display increased muscle stress-sensitivity to physical exercise when performed under stress conditions such as a forced swimming test. Under these conditions, they develop muscle atrophy, predominantly affecting trunk muscles and leading to severe kyphosis (PubMed:21858002). The number of satellite cells in uninjured adult muscle is reduced. After one single cardiotoxin-induced injury, a correct restoration of the muscle fibers is seen in skeletal muscle, whereas after two successive injuries, regeneration is completely abolished (PubMed:21131290).|||N-glycosylated.|||Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis. Regulates the calcium level of the ER by protecting the calcium pump ATP2A2 against the oxidoreductase ERO1A-mediated oxidative damage. Within the ER, ERO1A activity increases the concentration of H(2)O(2), which attacks the luminal thiols in ATP2A2 and thus leads to cysteinyl sulfenic acid formation (-SOH) and SEPN1 reduces the SOH back to free thiol (-SH), thus restoring ATP2A2 activity (PubMed:25452428). Acts as a modulator of ryanodine receptor (RyR) activity: protects RyR from oxidation due to increased oxidative stress, or directly controls the RyR redox state, regulating the RyR-mediated calcium mobilization required for normal muscle development and differentiation (By similarity). Essential for muscle regeneration and satellite cell maintenance in skeletal muscle (PubMed:21131290).|||The N-terminus (first 61 amino acids) contains an endoplasmic reticulum addressing and retention targeting signal. http://togogenome.org/gene/10090:Lrwd1 ^@ http://purl.uniprot.org/uniprot/Q8BUI3 ^@ Caution|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRWD1 family.|||Integral component of the ORC complex (By similarity). Directly interacts with CDT1, GMNN and ORC2. Interacts with ORC2 only when non-ubiquitinated; this interaction prevents LRWD1 ubiquitination and degradation. Some of these interactions are regulated in a cell-cycle dependent manner. Interaction with ORC1 occurs predominantly during G1. Association with phosphorylated ORC1 during mitosis is not efficient. Interaction with CDT1 occurs during G1 phase, as well as during mitosis with phosphorylated CDT1. Interaction with GMNN occurs from G1/S to mitosis. Interaction with ORC2 is observed throughout the cell cycle. The stoichiometry of the ORCA/ORC/CDT1/GMNN complex is 1:1:1:2 (By similarity). Interacts with CUL4A and DDB1; this interaction may lead to ubiquitination (By similarity).|||Nucleus|||Probable cloning artifact.|||Reported to be testis-specific (PubMed:20180869). However the transcript is found in many tissues, suggesting that the protein is present in many tissues.|||Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation (By similarity). Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability.|||Testis-specific.|||The entire WD repeat region is required for the interaction with ORC, CDT1 and GMNN, as well as for association with chromatin and for binding to histone H3 and H4 trimethylation marks H3K9me3 and H4K20me3 (By similarity). Centrosomal localization requires additional conformation.|||Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination leading to proteasomal degradation. Ubiquitination occurs within the WD repeats at the end of the G1 phase. Ubiquitination may be catalyzed by the CUL4-DDB1 E3 ubiquitin-protein ligase complex and other E3 ligases (By similarity).|||centromere|||centrosome|||kinetochore|||telomere http://togogenome.org/gene/10090:Cep83 ^@ http://purl.uniprot.org/uniprot/Q9D5R3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP83 family.|||Component of the distal appendage region of the centriole involved in the initiation of primary cilium assembly. May collaborate with IFT20 in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium during the initiation of primary cilium assembly.|||Interacts with CEP164 and IFT20.|||centriole http://togogenome.org/gene/10090:Ifna11 ^@ http://purl.uniprot.org/uniprot/A0A7R8C4Y5|||http://purl.uniprot.org/uniprot/Q61716 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Has antiviral and antiproliferative activities (PubMed:15254193). Produced by macrophages and stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase (By similarity). During viral infection, mediates antiviral effect, either directly by inducing interferon-stimulated genes, either indirectly through stimulation of natural killer cells enabling them to control viral replication (PubMed:22912583).|||N-glycosylated (PubMed:15254193).|||Secreted http://togogenome.org/gene/10090:Myo18b ^@ http://purl.uniprot.org/uniprot/E9PV66 ^@ Caution|||Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Plek2 ^@ http://purl.uniprot.org/uniprot/Q9WV52 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ May help orchestrate cytoskeletal arrangement. Contribute to lamellipodia formation. Overexpression of pleckstrin 2 causes large lamellipodia and peripheral ruffle formation.|||Ubiquitous. Most abundant in the thymus, large bowel, small bowel, stomach, and prostate.|||cytoskeleton|||lamellipodium membrane http://togogenome.org/gene/10090:Or11g27 ^@ http://purl.uniprot.org/uniprot/L7N1Y2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mettl26 ^@ http://purl.uniprot.org/uniprot/Q9DCS2 ^@ Similarity ^@ Belongs to the UPF0585 family. http://togogenome.org/gene/10090:Amd1 ^@ http://purl.uniprot.org/uniprot/P0DMN7 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic AdoMetDC family.|||Binds 1 pyruvoyl group covalently per subunit.|||Embryonic lethal with developmental arrest between E3.5 and E6.5. Arrest of blastocysts cultured in vitro is rescued by the addition of spermidine.|||Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.|||Expressed in embryonic stem cells; subsequently down-regulated in differentiating neural precursor cells.|||Heterotetramer of two alpha and two beta chains.|||Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The post-translation cleavage follows an unusual pathway, termed non-hydrolytic serinolysis, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl group blocking the N-terminus of the alpha chain. http://togogenome.org/gene/10090:Sel1l3 ^@ http://purl.uniprot.org/uniprot/Q80TS8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rnf139 ^@ http://purl.uniprot.org/uniprot/Q7TMV1 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated. Ubiquitination is induced by sterol and leads to ist degradation via the ubiquitin-proteasome pathway.|||E3-ubiquitin ligase; acts as a negative regulator of cell proliferation through mechanisms involving G2/M arrest and cell death. Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER). Affects SREBP processing by hindering the SREBP-SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression. Involved in the sterol-accelerated degradation of HMGCR. This is achieved through binding to INSIG1 and/or INSIG2 at the ER membrane. In addition, interaction of RNF139 with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR, leading to ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Required for INSIG1 ubiquitination. May be required for EIF3 complex ubiquitination.|||Endoplasmic reticulum membrane|||Interacts with VHL. Interacts with MHC class I and HM13. Component of SCAP-SREBP complex composed of SREBF2, SCAP and RNF139; the complex hampers the interaction between SCAP and SEC24B, thereby reducing SREBF2 proteolytic processing. Interacts with SREBF2 (via C-terminal domain). Interacts with SCAP; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP-SREBP complex. Interacts with SEC24B. Interacts with INSIG1 and INSIG2. Interacts with EIF3F and EIF3H; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner. Interacts with XBP1 isoform 1; the interaction induces ubiquitination and degradation of XBP1 isoform 1. Interacts with AUP1, AMFR and UBE2G2; interaction with AUP1 facilitates interaction of RNF139 with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase AMFR/gp78, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation.|||The RING-type zinc finger domain may be essential for ubiquitin ligase activity. http://togogenome.org/gene/10090:Klhl12 ^@ http://purl.uniprot.org/uniprot/Q8BZM0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ COPII-coated vesicle|||Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A. Interacts with DRD4, KLHL2 and SEC31A. Interacts with PEF1 and PDCD6/ALG-2; interaction takes place in response to cytosolic calcium increase and leads to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B).|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport. The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export. As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3. The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins.|||The BTB domain is required for interaction with CUL3.|||Ubiquitinated by the SCF(FBXL17) complex, leading to its degradation by the proteasome: ubiquitination by the SCF(FBXL17) complex takes place when aberrant BTB domain dimers are formed. http://togogenome.org/gene/10090:Manea ^@ http://purl.uniprot.org/uniprot/Q6NXH2 ^@ PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 99 family.|||Golgi apparatus membrane|||Undergoes proteolytic cleavage in the C-terminal region. http://togogenome.org/gene/10090:Cldnd1 ^@ http://purl.uniprot.org/uniprot/Q9CQX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family.|||Membrane http://togogenome.org/gene/10090:Nmur2 ^@ http://purl.uniprot.org/uniprot/Q8BZ39 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed primarily in brain tissues, more specifically in medulla and spinal cord. Widespread distribution in peripheral tissues.|||Receptor for the neuromedin-U and neuromedin-S neuropeptides. http://togogenome.org/gene/10090:Gm21155 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:St8sia3 ^@ http://purl.uniprot.org/uniprot/Q64689|||http://purl.uniprot.org/uniprot/Q9CUJ6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Catalyzes the transfer of sialic acid from a CMP-linked sialic acid donor onto the terminal sialic acid of an acceptor through alpha-2,8-linkages. Is active with alpha-2,3-linked, alpha-2,6-linked and alpha-2,8-linked sialic acid of N-linked oligosaccharides of glycoproteins and glycolipids. Displays preference for substrates with alpha-2,3-linked terminal sialic acid. It can form polysialic acid in vitro directly on alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid.|||Expressed first in 20 dpc fetal brain and decreases thereafter during development.|||Expressed in brain and testes.|||Golgi apparatus membrane|||Homodimer.|||Membrane http://togogenome.org/gene/10090:Fbxo31 ^@ http://purl.uniprot.org/uniprot/Q3TQF0 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the FBXO31 family.|||Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. Specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest (By similarity).|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex.|||Phosphorylation by ATM following gamma-irradiation results in its stabilization. http://togogenome.org/gene/10090:Acr ^@ http://purl.uniprot.org/uniprot/P23578|||http://purl.uniprot.org/uniprot/Q3ZB05 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Acrosin is the major protease of mammalian spermatozoa. It is a serine protease of trypsin-like cleavage specificity, it is synthesized in a zymogen form, proacrosin and stored in the acrosome.|||Belongs to the peptidase S1 family.|||Heavy chain (catalytic) and a light chain linked by two disulfide bonds. Forms a heterodimer with SERPINA5 (By similarity).|||Heavy chain (catalytic) and a light chain linked by two disulfide bonds. Forms a heterodimer with SERPINA5.|||Inhibited by SERPINA5. http://togogenome.org/gene/10090:Maf1 ^@ http://purl.uniprot.org/uniprot/Q9D0U6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAF1 family.|||Cytoplasm|||Interacts with TFIIIB subunits BRF1 and BRF2. Interacts with Pol III subunit POLR3F. Interacts with TFIIIC subunit GTF3C1.|||MAF1 deficient mice display a decreased metabolic efficiency. Constitutive high levels of Pol III transcription reprogram central metabolic pathways and waste metabolic energy through a futile RNA cycle (PubMed:30429315, PubMed:25934505). MAF1 down-regulation also alters the expression of genes involved in lipid and sugar metabolism (PubMed:30110641).|||Nucleus|||Phosphorylated at Ser-60, Ser-68 and Ser-75; the major sites of phosphorylation. Nuclear accumulation correlates with a concomitant dephosphorylation. Phosphorylation may attenuate its RNA polymerase III-repressive function (By similarity).|||Plays a role in the repression of RNA polymerase III-mediated transcription in response to changing nutritional, environmental and cellular stress conditions to balance the production of highly abundant tRNAs, 5S rRNA, and other small non-coding RNAs with cell growth and maintenance (By similarity). Also plays a key role in cell fate determination by promoting mesorderm induction and adipocyte differentiation (PubMed:30110641). Mechanistically, associates with the RNA polymerase III clamp and thereby impairs its recruitment to the complex made of the promoter DNA, TBP and the initiation factor TFIIIB. When nutrients are available and mTOR kinase is active, MAF1 is hyperphosphorylated and RNA polymerase III is engaged in transcription. Stress-induced MAF1 dephosphorylation results in nuclear localization, increased targeting of gene-bound RNA polymerase III and a decrease in the transcriptional readout. Additionally, may also regulate RNA polymerase I and RNA polymerase II-dependent transcription through its ability to regulate expression of the central initiation factor TBP (By similarity).|||Sumoylated with SUMO1 and SUMO2, mainly on Lys-35. Desumoylated by SENP1. SUMOylation promotes the ability of MAF1 to repress transcription and suppress colony formation (By similarity). http://togogenome.org/gene/10090:Dact2 ^@ http://purl.uniprot.org/uniprot/Q7TN08 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the dapper family.|||Can form homodimers and heterodimers with DACT1 or DACT3. Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, CSNK2B, DVL1, DVL2, DVL3, VANGL1, VANGL2, TGFBR1, CTNNB1, CTNND2, CTNND1, LEF1, TCF7, TCF7L1 and HDAC1.|||Expressed in kidney (inner medullary collecting duct). Expressed in epidermal keratinocytes and hair follicles.|||Expressed throughout the epiblast at the onset of gastrulation and in somites, the neural tube and gut at later stages of development. In the developing kidney is expressed in the ureteric bud/collecting duct epithelium.|||Involved in non-canonical Wnt signaling only when massively overexpressed.|||Involved in regulation of intracellular signaling pathways during development. Negatively regulates the Nodal signaling pathway, possibly by promoting the lysosomal degradation of Nodal receptors, such as TGFBR1. May be involved in control of the morphogenetic behavior of kidney ureteric bud cells by keeping cells epithelial and restraining their mesenchymal character. May play an inhibitory role in the re-epithelialization of skin wounds by attenuating TGF-beta signaling.|||The C-terminal PDZ-binding motif may mediate interaction with the PDZ domains of DSH (Dishevelled) family proteins. http://togogenome.org/gene/10090:Sgk2 ^@ http://purl.uniprot.org/uniprot/Q3UW73|||http://purl.uniprot.org/uniprot/Q9QZS5 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Activated by phosphorylation on Ser-356 by an unknown kinase (may be mTORC2 but not confirmed), transforming it into a substrate for PDPK1 which then phosphorylates it on Thr-193.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm|||Not regulated by serum or glucocorticoids.|||Nucleus|||Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, survival and proliferation. Up-regulates Na(+) channels: SCNN1A/ENAC, K(+) channels: KCNA3/Kv1.3, KCNE1 and KCNQ1, amino acid transporter: SLC6A19, glutamate transporter: SLC1A6/EAAT4, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase.|||Two specific sites, one in the kinase domain (Thr-193) and the other in the C-terminal regulatory region (Ser-356), need to be phosphorylated for its full activation. http://togogenome.org/gene/10090:Sgpp1 ^@ http://purl.uniprot.org/uniprot/Q9JI99 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type 2 lipid phosphate phosphatase family.|||Cell membrane|||Endoplasmic reticulum membrane|||Highly expressed in liver and kidney. Expressed in epidermis, in the stratum granulosum and the stratum spinosum (PubMed:23637227).|||Inhibited by NaF, sodium orthovanadate, propanolol, and N-ethylmaleimide.|||Mutants appear normal at birth, but during the first week of life they exhibit stunted growth and suffer desquamation, with most dying before weaning (PubMed:23637227). Their subcorneal layers, including the stratum granulosum, stratum spinosum, and stratum basale, are significantly thicker, whereas the stratum corneum is thinner than in wild-type mic (PubMed:23637227).|||Specifically dephosphorylates sphingosine 1-phosphate (S1P), dihydro-S1P, and phyto-S1P (PubMed:10859351, PubMed:11756451). Does not act on ceramide 1-phosphate, lysophosphatidic acid or phosphatidic acid. Sphingosine-1-phosphate phosphatase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. Regulates the intracellular levels of the bioactive sphingolipid metabolite S1P that regulates diverse biological processes acting both as an extracellular receptor ligand or as an intracellular second messenger (PubMed:10859351, Ref.2). Involved in efficient ceramide synthesis from exogenous sphingoid bases. Converts S1P to sphingosine, which is readily metabolized to ceramide via ceramide synthase (PubMed:12235122, PubMed:17895250). In concert with sphingosine kinase 2 (SphK2), recycles sphingosine into ceramide through a phosphorylation/dephosphorylation cycle (PubMed:17895250). Regulates endoplasmic-to-Golgi trafficking of ceramides, resulting in the regulation of ceramide levels in the endoplasmic reticulum, preferentially long-chain ceramide species, and influences the anterograde membrane transport of both ceramide and proteins from the endoplasmic reticulum to the Golgi apparatus (By similarity). The modulation of intracellular ceramide levels in turn regulates apoptosis (PubMed:12235122). Via S1P levels, modulates resting tone, intracellular Ca(2+) and myogenic vasoconstriction in resistance arteries. Also involved in unfolded protein response (UPR) and ER stress-induced autophagy via regulation of intracellular S1P levels (By similarity). Involved in the regulation of epidermal homeostasis and keratinocyte differentiation (PubMed:23637227). http://togogenome.org/gene/10090:Mrps34 ^@ http://purl.uniprot.org/uniprot/Q9JIK9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrion-specific ribosomal protein mS34 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion|||Required for mitochondrial translation, plays a role in maintaining the stability of the small ribosomal subunit and the 12S rRNA that are required for mitoribosome formation.|||Widely expressed (at protein liver). http://togogenome.org/gene/10090:Gm7609 ^@ http://purl.uniprot.org/uniprot/A0A668KL92 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Marf1 ^@ http://purl.uniprot.org/uniprot/Q8BJ34 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in germ cells in quiescent oocytes isolated from newborn P0 ovaries that have not yet commenced the growth phase. Protein levels increase after oocytes initiate growth, and follicular development reach the primary follicle stage at P6. Thereafter, protein levels remain at the similar levels (at protein level).|||Essential regulator of oogenesis required for female meiotic progression to repress transposable elements and preventing their mobilization, which is essential for the germline integrity. Probably acts via some RNA metabolic process, equivalent to the piRNA system in males, which mediates the repression of transposable elements during meiosis by forming complexes composed of RNAs and governs the methylation and subsequent repression of transposons. Also required to protect from DNA double-strand breaks.|||Female infertility due to oocyte meiotic arrest at the germinal vesicle stage: ovaries look normal, but oocytes do not resume meiosis even after a superovulatory regimen of gonadotropins and are ovulated at the immature germinal vesicle stage. Oocytes display strong up-regulation of a transcripts, increased retrotransposon expression, defective cytoplasmic maturation, and meiotic arrest. Mutant males are fertile.|||Interacts with LIMK2.|||Peroxisome|||Predominantly present in oocytes and barely detectable in granulosa cells (at protein level). http://togogenome.org/gene/10090:Fam107a ^@ http://purl.uniprot.org/uniprot/Q78TU8 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in septum, the neocortex, the CA3 region of the hippocampus and the cerebellum (at protein level).|||Interacts with ACTB (PubMed:21969592). Interacts with F-actin (PubMed:21969592). Interacts with PRDX1 (PubMed:21969592). Interacts with COMMD1; this interaction stabilizes COMMD1 in the nucleus (By similarity). Interacts with MAP1A (By similarity).|||Nucleus|||Stress-inducible actin-binding protein that plays a role in synaptic and cognitive functions by modulating actin filamentous (F-actin) dynamics (PubMed:21969592). Mediates polymerization of globular actin to F-actin (PubMed:21969592). Also binds to, stabilizes and bundles F-actin (PubMed:21969592). Involved in synaptic function by regulating neurite outgrowth in an actin-dependent manner and for the acquisition of hippocampus-dependent cognitive function, such as learning and long-term memory (PubMed:21969592). Plays a role in the actin and microtubule cytoskeleton organization; negatively regulates focal adhesion (FA) assembly promoting malignant glial cell migration in an actin-, microtubule- and MAP1A-dependent manner. Also involved in neuroblastoma G1/S phase cell cycle progression and cell proliferation inhibition by stimulating ubiquitination of NF-kappa-B subunit RELA and NF-kappa-B degradation in a COMMD1- and actin-dependent manner. May play a role in tumor development (By similarity).|||Synapse|||Up-regulated in the hypothalamic paraventricular nucleus (PVN) and the CA3 region of the hippocampus of the brain in response to postnatal maternal separation or food deprivation and glucocorticoids stimulation in adult animals (PubMed:21969592). Up-regulated in CA1, CA3 and dente gyrus regions of the hippocampus in response to acute social defeat stress or glucocorticoids stimulation (PubMed:25637808).|||focal adhesion|||ruffle membrane|||stress fiber http://togogenome.org/gene/10090:Tada2a ^@ http://purl.uniprot.org/uniprot/Q8CHV6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (By similarity). Required for the function of some acidic activation domains, which activate transcription from a distant site (By similarity). Binds double-stranded DNA (PubMed:16299514). Binds dinucleosomes, probably at the linker region between neighboring nucleosomes (PubMed:16299514). Plays a role in chromatin remodeling (By similarity). May promote TP53/p53 'Lys-321' acetylation, leading to reduced TP53 stability and transcriptional activity (By similarity). May also promote XRCC6 acetylation thus facilitating cell apoptosis in response to DNA damage (By similarity).|||Interacts with GCN5. Interacts with NR3C1. Associated with the P/CAF protein in the PCAF complex. Component of the PCAF complex, at least composed of TADA2L/ADA2, TADA3L/ADA3, TAF5L/PAF65-beta, TAF6L/PAF65-alpha, TAF10/TAFII30, TAF12/TAFII20, TAF9/TAFII31 and TRRAP. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1. Interacts with CCDC134.|||Nucleus http://togogenome.org/gene/10090:Or4k37 ^@ http://purl.uniprot.org/uniprot/Q7TQY6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prrc2a ^@ http://purl.uniprot.org/uniprot/Q7TSC1 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||May play a role in the regulation of pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Ptov1 ^@ http://purl.uniprot.org/uniprot/Q91VU8 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 25 family. PTOV1 subfamily.|||Cell membrane|||Cytoplasm|||Despite sequence similarity to MED25, to date this protein has not been identified as a component of the Mediator complex.|||May activate transcription. Required for nuclear translocation of FLOT1. Promotes cell proliferation.|||May interact with CREBBP. Interacts with FLOT1.|||Nucleus|||Ubiquitinated by the CRL2(KLHDC2) complex, which recognizes the diglycine (Gly-Gly) at the C-terminus, leading to its degradation. Ubiquitinated by the CRL2(APPBP2) complex, which recognizes the Arg-Xaa-Xaa-Gly sequence at the C-terminus, leading to its degradation.|||perinuclear region http://togogenome.org/gene/10090:Anxa6 ^@ http://purl.uniprot.org/uniprot/F8WIT2|||http://purl.uniprot.org/uniprot/P14824|||http://purl.uniprot.org/uniprot/Q3TUI1|||http://purl.uniprot.org/uniprot/Q3UI56 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||Cytoplasm|||May associate with CD21. May regulate the release of Ca(2+) from intracellular stores.|||Melanosome|||Seems to bind one calcium ion with high affinity. http://togogenome.org/gene/10090:Treml4 ^@ http://purl.uniprot.org/uniprot/Q3LRV9 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Induced by synthetic TLR7 ligand gardiquimod (GRD) in cultured splenic macrophages.|||Interacts with TYROBP/DAP12.|||No visible phenotype (PubMed:22210914). Mutant mice are born at the expected Mendelian frequency and are fertile and healthy (PubMed:22210914). In response to gardiquimod (GRD) or Resiquimod (R-848), 2 synthetic TLR7 ligands, levels of TNF, IL12B, IFNB1 and CXCL10 in splenic macrophages and in serum are severely reduced (PubMed:25848864). In response to CpG DNA, a TLR9 ligand, levels of TNF and IL12B but not IFNB1 and CXCL10 are severely reduced (PubMed:25848864). In response to infection with influenza virus (strain A/PuertoRico/8/34 (PR8)) the production of TNF, IL12B, IFNB1 and CXCL10 is severely impaired, the viral load is higher in the lungs, recovery after weight loss and survival are also impaired (PubMed:25848864). No defects in response to lipopolysaccharide (LPS) (PubMed:25848864). Reduced symptom severity in a mouse model for the autoimmune disease systemic lupus erythematosus (SLE) (PubMed:25848864).|||Positively regulates Toll-like receptor signaling via TLR7, TLR9 and TLR13 in neutrophils and splenic macrophages (PubMed:25848864). Regulates TLR7 signaling by controlling ligand-induced recruitment of TLR7 from the endoplasmic reticulum to endosomes and lysosomes (PubMed:25848864). Positively regulates Toll-like receptor TLR9-induced production of inflammatory cytokines but is dispensable for IFNB1 production (PubMed:25848864). Involved in the anti-viral response to several viruses including influenza virus, vesicular stomatitis virus and cytomegalovirus (PubMed:25848864). Binds to late apoptotic, and necrotic cells, but not living or early apoptotic cells, but is not essential for uptake of dying cells by dendritic cells (DCs) (PubMed:22210914, PubMed:19155473, PubMed:25848864). Does not bind nucleic acids (PubMed:25848864). May participate in antigen presentation (PubMed:22210914).|||Predominantly expressed in spleen, with highest levels on selected populations of macrophages, including red pulp macrophages, and on subsets of dendritic cells (DC), mostly on CD8alpha(+) DC (at protein level) (PubMed:19155473, PubMed:22210914, PubMed:25848864). Also expressed on blood and spleen Ly6C(low) monocytes (at protein level) (PubMed:22210914). Not expressed on lymphocytes or granulocytes (at protein level) (PubMed:19155473, PubMed:22210914).|||The cytoplasmic tail appears to be dispensable for TLR7-mediated signaling. http://togogenome.org/gene/10090:Stpg1 ^@ http://purl.uniprot.org/uniprot/Q9D2F5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ After exposure to alkylating agent, significantly suppresses the depolarization of the mitochondrial membrane and the activation of BAK and caspase-3, all of which are hallmarks for the induction of apoptosis.|||Belongs to the STPG1 family.|||Cytoplasm|||May positively contribute to the induction of apoptosis triggered by O(6)-methylguanine.|||Nucleus http://togogenome.org/gene/10090:Ets1 ^@ http://purl.uniprot.org/uniprot/E9PWI8|||http://purl.uniprot.org/uniprot/P27577|||http://purl.uniprot.org/uniprot/Q540Q5|||http://purl.uniprot.org/uniprot/Q8BVW8|||http://purl.uniprot.org/uniprot/Q8K3Q9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoinhibited by a module composed of four alpha helices (HI-1, HI-2, H4, and H5) that flank the DNA-binding ETS domain, reducing the affinity for DNA (PubMed:15591056, PubMed:15994560). Phosphorylation by CaMK2/CaMKII in response to calcium signaling decreases affinity for DNA (PubMed:15994560).|||Belongs to the ETS family.|||Binds DNA as a homodimer; homodimerization is required for transcription activation (PubMed:15591056). Interacts with MAF and MAFB (PubMed:9566892, PubMed:10790365). Interacts with PAX5; the interaction alters DNA-binding properties (PubMed:11779502). Interacts with DAXX. Interacts with UBE2I. Interacts with SP100; the interaction is direct and modulates ETS1 transcriptional activity (By similarity).|||Cytoplasm|||Nucleus|||Phosphorylation at Ser-251, Ser-282 and Ser-285 by CaMK2/CaMKII in response to calcium signaling decreases affinity for DNA: an increasing number of phosphoserines causes DNA-binding to become progressively weaker.|||Sumoylated on Lys-15 and Lys-227, preferentially with SUMO2; which inhibits transcriptional activity.|||Transcription factor (PubMed:15994560). Directly controls the expression of cytokine and chemokine genes in a wide variety of different cellular contexts (By similarity). May control the differentiation, survival and proliferation of lymphoid cells (By similarity). May also regulate angiogenesis through regulation of expression of genes controlling endothelial cell migration and invasion (By similarity).|||Ubiquitinated; which induces proteasomal degradation. http://togogenome.org/gene/10090:Gbp8 ^@ http://purl.uniprot.org/uniprot/Q2V6D6 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. http://togogenome.org/gene/10090:Acsf3 ^@ http://purl.uniprot.org/uniprot/Q3URE1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester. May have some preference toward very-long-chain substrates.|||Mitochondrion http://togogenome.org/gene/10090:Pdzrn3 ^@ http://purl.uniprot.org/uniprot/Q69ZS0 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated.|||Cytoplasm|||E3 ubiquitin-protein ligase. Plays an important role in regulating the surface level of MUSK on myotubes. Mediates the ubiquitination of MUSK, promoting its endocytosis and lysosomal degradation. Might contribute to terminal myogenic differentiation.|||First detected at the NMJ at approximately 16.5 dpc, when NMJs have just formed. As the NMJ grows and matures, expression levels increase in concert with that of acetylcholine receptors. Levels stay relatively high until 14 days after birth, but decrease significantly by 21 days. Up-regulated during myogenic differentiation in C2C12 cells and during injury-induced muscle regeneration.|||Highly expressed in skeletal and cardiac muscle and at lower levels in spinal cord and brain (at protein level). Also expressed in kidney and lung. In muscles, concentrated at the neuromuscular junction (NMJ).|||Interacts with NLGN1 and EFNB2 (By similarity). Interacts with UBE2D2 and with MUSK via the first PDZ domain. In myotubes, the interaction between PDZRN3 and MUSK is enhanced upon agrin stimulation.|||Synapse|||The RING-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Rln1 ^@ http://purl.uniprot.org/uniprot/A2RTV8 ^@ Subcellular Location Annotation|||Subunit ^@ Heterodimer of a B chain and an A chain linked by two disulfide bonds.|||Secreted http://togogenome.org/gene/10090:Gnat3 ^@ http://purl.uniprot.org/uniprot/B2RVZ3|||http://purl.uniprot.org/uniprot/Q3V3I2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||Cytoplasm|||Expressed in taste buds (sensory organs of clustered epithelial cells) of the circumvallate and fungiform papillae of the tongue as well as in palatal taste buds at protein level. Expressed in enteroendocrine cells of the gut, such as in subsets of enteroendocrine cells in the midjejunum and brush cells. Detected also in spermatozoa.|||From week 1 to 7, the number of cells expressing GNAT3 in single taste buds increases within fungiform papilla; by week 7, the number reached the value found in adults. Expressed in cell bodies and axons of facial motor neurons at 10.5 dpc.|||G proteins are composed of 3 units; alpha, beta and gamma, respectively GNAT3, GNB1 and GNG13 for Gustducin heterotrimer for bitter taste transduction. The alpha chain contains the guanine nucleotide binding site. Gustducin heterotrimer may also be composed of GNAT3, GNB3 and GNG13.|||Guanine nucleotide-binding protein (G protein) alpha subunit playing a prominent role in bitter and sweet taste transduction as well as in umami (monosodium glutamate, monopotassium glutamate, and inosine monophosphate) taste transduction. Transduction by this alpha subunit involves coupling of specific cell-surface receptors with a cGMP-phosphodiesterase; Activation of phosphodiesterase lowers intracellular levels of cAMP and cGMP which may open a cyclic nucleotide-suppressible cation channel leading to influx of calcium, ultimately leading to release of neurotransmitter. Indeed, denatonium and strychnine induce transient reduction in cAMP and cGMP in taste tissue, whereas this decrease is inhibited by GNAT3 antibody. Gustducin heterotrimer transduces response to bitter and sweet compounds via regulation of phosphodiesterase for alpha subunit, as well as via activation of phospholipase C for beta and gamma subunits, with ultimate increase inositol trisphosphate and increase of intracellular Calcium. GNAT3 can functionally couple to taste receptors to transmit intracellular signal: receptor heterodimer TAS1R2/TAS1R3 senses sweetness and TAS1R1/TAS1R3 transduces umami taste, whereas the T2R family GPCRs act as bitter sensors. Functions also as lumenal sugar sensors in the gut to control the expression of the Na+-glucose transporter SGLT1 in response to dietaty sugar, as well as the secretion of Glucagon-like peptide-1, GLP-1 and glucose-dependent insulinotropic polypeptide, GIP. Thus, may modulate the gut capacity to absorb sugars, with implications in malabsorption syndromes and diet-related disorders including diabetes and obesity.|||Mice are not affected in their tasting ability for salty (NaCl) and sour (HCl) stimuli, which are known not to be mediated by G proteins; but, they exhibit a significant reduction in the ability to taste the bitter compounds denatonium and quinine as well as the sweet compounds sucrose and SC45647, a guanidine sweetener. The incidence of cells responding to bitter stimulus is also reduced by seventy per cent. The residual behavioral response to bitter and sweet taste in these deficient mice suggests that there is alternative mechanism to compensate. However, transgenic expression of Gnat3 in these deficient mice restores responsiveness to both bitter and sweet compounds, whereas expression of mutated 'Gly-352' transgene do not. Furthermore, in wild-type mice, this mutated transgene acts as dominant-negative by inhibition of endogenous Gnat3 interactions with taste receptors. Mice show less preference for acesulfame-K, dulcin, fructose, D-phenylalanine, L-proline, D-tryptophan, saccharin, sweetener SC45647 and sucrose; Furthermore, in their gut, sugar or sweeteners do not increase SGLT1 expression and glucose-absorptive capacity compared to wild-type mice and the ingestion of glucose reveals deficiencies in secretion of GLP-1 and regulation of plasma insulin and glucose. Mice lacking GNAT3 show less preference for umami compounds such as monosodium glutamate (MSG) and no preference for inosine monophosphate (IMP) whereas wild-type mice strongly prefer IMP. The response to umami signals implicates the anteriorly placed taste buds of the tongue, and not the posterior part.|||Potential N-myristoylation may anchor alpha-subunit to the inner surface of plasma membrane. http://togogenome.org/gene/10090:Sult1c2 ^@ http://purl.uniprot.org/uniprot/Q9D939 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Cytoplasm|||Highly expressed in stomach and kidney.|||Lysosome|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation. Sulfonates p-nitrophenol, a small phenolic compond (PubMed:12164856). Does not sulfonate steroids, dopamine, acetaminophen, or alpha-naphthol (PubMed:12164856). http://togogenome.org/gene/10090:Dpp3 ^@ http://purl.uniprot.org/uniprot/Q3UDF3|||http://purl.uniprot.org/uniprot/Q99KK7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M49 family.|||Binds 1 zinc ion per subunit.|||Cleaves and degrades bioactive peptides, including angiotensin, Leu-enkephalin and Met-enkephalin. Also cleaves Arg-Arg-beta-naphthylamide (in vitro).|||cytosol http://togogenome.org/gene/10090:Etfrf1 ^@ http://purl.uniprot.org/uniprot/Q91V16 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a regulator of the electron transfer flavoprotein by promoting the removal of flavin from the ETF holoenzyme (composed of ETFA and ETFB).|||Belongs to the complex I LYR family.|||Mitochondrion|||homotetramer. Interacts with NDUFAB1. Interacts with ETFA. Interacts with ETFB. http://togogenome.org/gene/10090:Hsd3b4 ^@ http://purl.uniprot.org/uniprot/Q3UIU9|||http://purl.uniprot.org/uniprot/Q61767 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Expression between 15-20 days post-implantation occurs only in the kidney of the male fetus and not in the female, whereas a similar expression is found in adult male and female kidneys.|||Kidney (at protein level); found only in the cortex, appears to be associated with the proximal tubules; and a minor expression in testis.|||Mitochondrion membrane|||Responsible for the reduction of the oxo group on the C-3 of 5alpha-androstane steroids. Catalyzes the conversion of dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Does not function as an isomerase. http://togogenome.org/gene/10090:Gpr156 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0P3|||http://purl.uniprot.org/uniprot/Q6PCP7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.|||Cell membrane|||Membrane|||Orphan receptor.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Hnrnpll ^@ http://purl.uniprot.org/uniprot/Q921F4 ^@ Function|||Induction|||Subunit ^@ Interacts with HNRNPL.|||RNA-binding protein that functions as regulator of alternative splicing for multiple target mRNAs, including PTPRC/CD45 and STAT5A. Required for alternative splicing of PTPRC.|||Up-regulated in stimulated T-cells. http://togogenome.org/gene/10090:Vps39 ^@ http://purl.uniprot.org/uniprot/Q8R5L3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VAM6/VPS39 family.|||Cytoplasm|||Embryonic lethal, before E6.5.|||Homooligomer (By similarity). Interacts with TGFBR2 and, less efficiently, with TGFBR1; interaction with TGFBR2 is independent of the receptor kinase activity and of the presence of TGF-beta. Also interacts with ACVR2B, but not with BMPR2. Interacts with SMAD4, preferentially following TGF-beta treatment (By similarity). Component of the putative homotypic fusion and vacuole protein sorting (HOPS) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS39 and VPS41. Interacts with PLEKHM2; involved in VPS39 recruitment to ARL8B-containing lysosomes (By similarity). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (PubMed:21411634). Interacts with STX17; this interaction is increased in the absence of TMEM39A (By similarity).|||Late endosome membrane|||Lysosome membrane|||May play a role in clustering and fusion of late endosomes and lysosomes (By similarity). Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2-dependent transcription (By similarity).|||Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Acts as a component of the putative HOPS endosomal tethering complex which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes. Required for fusion of endosomes and autophagosomes with lysosomes (By similarity). http://togogenome.org/gene/10090:Cda ^@ http://purl.uniprot.org/uniprot/P56389 ^@ Function|||Similarity|||Subunit ^@ Belongs to the cytidine and deoxycytidylate deaminase family.|||Homotetramer.|||This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis. http://togogenome.org/gene/10090:Cib4 ^@ http://purl.uniprot.org/uniprot/Q9D9N5 ^@ Miscellaneous|||Subunit|||Tissue Specificity ^@ Expressed weakly in megakaryocytes and endothelial cells.|||Interacts with ITGA2B (via C-terminus cytoplasmic tail region); the interaction is stabilized/increased in a calcium- and magnesium-dependent manner.|||The binding of either calcium or magnesium may significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form). http://togogenome.org/gene/10090:Rab35 ^@ http://purl.uniprot.org/uniprot/Q6PHN9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Endosome|||Interacts with DENND1A and DENND1B; in a nucleotide-dependent manner (PubMed:20159556, PubMed:26774822). Interacts with DENND1C; weak interaction which is nucleotide-independent (By similarity). Interacts (GTP-bound form) with ACAP2 and MICALL1; the interaction is direct and probably recruits ACAP2 and MICALL1 to membranes (PubMed:23572513). Interacts with EHD1; the interaction is indirect through MICALL1 and probably recruits EHD1 to membranes (PubMed:23572513). Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-72 disrupts these interactions (By similarity).|||Melanosome|||Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (PubMed:20159556, PubMed:26774822).|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes.|||clathrin-coated pit|||clathrin-coated vesicle http://togogenome.org/gene/10090:Atosa ^@ http://purl.uniprot.org/uniprot/Q69ZK7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATOS family.|||Nucleus|||The protein contains 2 transactivation domains (TAD). Each of these domains may be required for transcriptional activation of a subset of target genes.|||Transcription regulator that syncronizes transcriptional and translational programs to promote macrophage invasion of tissues. http://togogenome.org/gene/10090:Mlip ^@ http://purl.uniprot.org/uniprot/Q5FW52 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Directly interacts with LMNA (PubMed:21498514, PubMed:26436652). Interacts with ISL1 (via N-terminal domain); the interaction represses ISL1 transactivator activity (PubMed:22343712, PubMed:36112854). Interactions of ISL1 with MLIP1 and GCN5/KAT2A may be mutually exclusive (PubMed:36112854).|||First detected in heart at 8.5 dpc, becomes progressively restricted to heart from 9.5 dpc to 15.5 dpc. At 9.5 dpc, transiently detected in the truck. From 11.5 dpc to 15.5 dpc, expression is higher in the ventricles of embryonic hearts. During embryogenesis, specifically expressed in cardiomyocytes. In neonatal mice, also expressed in the skeletal muscle. Myocardial expression continue in the adult heart.|||Knockout animals are obtained at the expected Mendelian ratio. They are viable and exhibit normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of AKT/mTOR pathways (PubMed:26359501, PubMed:26436652). In aged mutants, cardiac function is depressed with increased left ventricular dimension (PubMed:26436652). They show an impaired capacity to adapt to stress such as hypertrophy induced by isoproterenol (ISO). After 9 days of continuous ISO treatment, they display an increase in heart to body weight ratio, thickened interventricular septum and blunted contractile response compared to their wild type littermates (PubMed:26359501). Upon transverse aortic constriction (TAC), animals develop a dramatic cardiac dilation with a significant increase in left ventricular internal dimension and decreased in left ventricular wall thickness. While control mice exhibit a trend toward decreased cardiac contraction, the cardiac function in knockout animals is dramatically impaired after TAC. TAC induces a greater increase in the size of cardiomyocytes and more extensive fibrosis in hearts compared to the control ones (PubMed:26436652). Double knockouts for MLIP and LMNA die sooner than single LMNA knockout. They develop much more severe ventricular dilation and cardiac dysfunction (PubMed:26436652).|||May be ubiquitinated by UBE3C ubiquitin ligase; ubiquitination is followed by protein degradation.|||Nucleus|||Nucleus envelope|||PML body|||Predominantly expressed in the heart and skeletal muscle, but detected at lower levels in the lung and brain (at protein level) (PubMed:21498514, PubMed:22343712, PubMed:33802236). Also detected in smooth muscle, thymus and kidney (PubMed:21498514). In brain, expressed by a subpopulation of cells within the hippocampus and cortex (PubMed:21498514). In heart, expressed by cardiomyocytes (PubMed:21498514). Expression is reduced in hypertrophic hearts at the transcript level (PubMed:26359501, PubMed:22343712, PubMed:26436652). However, expression in hypertrophic hearts induced by transverse aortic constriction do not differ from control at the protein level (PubMed:26436652).|||Produced by an alternative transcription start site and by alternative splicing. The alternative exon 1, also called 1a, is expressed in heart and skeletal muscle, but not in brain.|||Produced by an alternative transcription start site. The alternative exon 1, also called 1b, is expressed in brain and skeletal muscle, but not in heart.|||Required for myoblast differentiation into myotubes, possibly acting as a transcriptional regulator of the myogenic program (PubMed:33802236). Required for cardiac adaptation to stress through integrated regulation of the AKT/mTOR pathways and FOXO1. Regulates cardiac homeostasis and plays a role in the protection against cardiac hypertrophy (PubMed:26359501, PubMed:22343712, PubMed:26436652). Binds chromatin (PubMed:33802236). May act as a transcriptional cofactor for ISL1, repressing its transcriptional activity (PubMed:22343712). May also repress MYOCD transcriptional activity (PubMed:22343712).|||Up-regulated by beta-catenin/CTNNB1 in mesenchymal stem cells (at protein level). This up-regulation may proceed through the down-regulation of UBE3C ubiquitin ligase by CTNNB1.|||cytosol|||sarcolemma http://togogenome.org/gene/10090:Vmn1r236 ^@ http://purl.uniprot.org/uniprot/Q05A06 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rtf2 ^@ http://purl.uniprot.org/uniprot/Q99K95 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the rtf2 family.|||Chromosome|||Interacts with DDI2; probably also interacts with DDI1.|||Replication termination factor which is a component of the elongating replisome. Required for ATR pathway signaling upon DNA damage and has a positive activity during DNA replication. Might function to facilitate fork pausing at replication fork barriers like the rDNA. May be globally required to stimulate ATR signaling after the fork stalls or encounters a lesion. Interacts with nascent DNA.|||Undergoes proteasomal degradation, via DDI1 and DDI2. Removal from stalled replisomes and degradation are required for genome stability. http://togogenome.org/gene/10090:Kctd19 ^@ http://purl.uniprot.org/uniprot/Q562E2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in adult testis.|||Identified in a complex with ZNF541, HDAC1 and HSPA2 (PubMed:18849567). Identified in a complex with ZNF541 and HDAC1 (PubMed:33961623). Identified in a complex with HDAC1, HDAC2, DNTTIP1 and ZNF541 (PubMed:35341968, PubMed:34075040).|||Males are infertile and spermatocytes fail to complete meiosis and show defects in metaphase I organization.|||Not detected in testis from neonates. Expression in testis is first detected 14 days after birth and increases thereafter. Highly expressed 30 and 84 days after birth.|||Nucleus|||Transcription regulator which is essential for male fertility and for the completion of meiotic prophase in spermatocytes (PubMed:33961623, PubMed:34075040, PubMed:35341968). Regulates progression of the pachytene stage of meiotic prophase and promotes the transcriptional activation activity ZNF541 (PubMed:35341968). Required for the organization of chromosomes during metaphase I (PubMed:33961623, PubMed:34075040). http://togogenome.org/gene/10090:Zng1 ^@ http://purl.uniprot.org/uniprot/Q8VEH6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although mice are viable and do not show visible phenotype, they display non-Mendelian inheritance (PubMed:35584702). Mice show impaired zinc homeostasis: they are sensitive to dietary zinc starvation and show decreased weight gain when fed a low zinc diet, due to failure to access existing zinc pools (PubMed:35584702). Impaired zinc homeostasis leads to mitochondrial dysfunction (PubMed:35584702). Mice also display kidney defects, characterized by hydronephrosis, hydroureters and duplicated ureters (PubMed:31862704).|||Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.|||Nucleus|||Present at high level in the nuclei of the ureteric bud cells in the developing kidneys.|||Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them (PubMed:35584702). Catalyzes zinc insertion into the active site of methionine aminopeptidase METAP1, which function to cleave the initiator methionine from polypeptides during or after protein translation (PubMed:35584702). Mechanistically, the N-terminal psi-PxLVp motif binds to the C6H2-type zinc finger of inactive form of METAP1 (PubMed:35584702). After formation of the docked complex, zinc is transferred from the CXCC motif in the GTPase domain of ZNG1 to the zinc binding site in the peptidase domain of METAP1 in a process requiring GTP hydrolysis (PubMed:35584702). GTP/GDP exchange is required for release of active METAP1 (PubMed:35584702). http://togogenome.org/gene/10090:Stmn2 ^@ http://purl.uniprot.org/uniprot/P55821|||http://purl.uniprot.org/uniprot/Q545S4 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15.5 dpc, mid to low expression throughout the midbrain, with more prominent levels in the telencephalon, especially in the intermediate zone, the midbrain roof, the olfactory epithelium, the inferior colliculus, and the medulla oblongata. telencephalon revealed concentrated (at protein level).|||Belongs to the stathmin family.|||Cytoplasm|||Endosome|||Golgi apparatus|||Interacts with ITM2C. Interacts with MAPK8. Interacts with KIFBP. Interacts (via the N-terminal region) with CIB1 (via C-terminal region); the interaction is direct, occurs in a calcium-dependent manner and attenuates the neurite outgrowth inhibition of STMN2.|||Membrane|||N-terminal palmitoylation promotes specific anchoring to the cytosolic leaflet of Golgi membranes and subsequent vesicular trafficking along dendrites and axons. Neuronal Stathmins are substrates for palmitoyltransferases ZDHHC3, ZDHHC7 and ZDHHC15 (By similarity).|||Neuron specific.|||Phosphorylated mostly by MAPK8, but also by MAPK9 and MAPK10 in the developing brain cortex.|||Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone.|||Sumoylated.|||axon|||growth cone|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Hmg20b ^@ http://purl.uniprot.org/uniprot/Q9Z104 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with the BRCA2 tumor suppressor protein (By similarity). Interacts with DTNB (PubMed:20530487).|||Nucleus|||Required for correct progression through G2 phase of the cell cycle and entry into mitosis. Required for RCOR1/CoREST mediated repression of neuronal specific gene promoters (By similarity).|||Widely expressed in adult tissues, particularly kidney, skin, testis and uterus. Highly expressed in embryonic tissues with high mitotic index, such as the proliferating ventricular zones of the fore-, mid- and hindbrain. http://togogenome.org/gene/10090:Htt ^@ http://purl.uniprot.org/uniprot/G3X9H5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the huntingtin family.|||Cytoplasm|||May play a role in microtubule-mediated transport or vesicle function.|||Nucleus http://togogenome.org/gene/10090:Nhp2 ^@ http://purl.uniprot.org/uniprot/Q9CRB2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL8 family.|||Cajal body|||Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. During assembly, the complex contains NAF1 instead of GAR1/NOLA1. The complex also interacts with TERC, which contains a 3'-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1.|||Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (By similarity).|||nucleolus http://togogenome.org/gene/10090:Arl13a ^@ http://purl.uniprot.org/uniprot/Q9D416 ^@ Similarity ^@ Belongs to the small GTPase superfamily. http://togogenome.org/gene/10090:Oaz1 ^@ http://purl.uniprot.org/uniprot/P54369 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ODC antizyme family.|||Interacts with ODC1 and thereby sterically blocks ODC homodimerization (By similarity). Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S proteasome (By similarity). Interacts with AZIN2; this interaction disrupts the interaction between the antizyme and ODC1 (PubMed:16916800, PubMed:18062773, PubMed:24967154). Interacts with FAM171A1 (By similarity).|||Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimer, and targets the monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome (PubMed:16916800, PubMed:18508777). Triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC (By similarity). Stabilizes AZIN2 by interfering with its ubiquitination (PubMed:18062773). Also inhibits cellular uptake of polyamines by inactivating the polyamine uptake transporter. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1. Involved in the translocation of AZIN2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol (PubMed:19449338). http://togogenome.org/gene/10090:Coq10a ^@ http://purl.uniprot.org/uniprot/E9Q3H6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the COQ10 family.|||Interacts with coenzyme Q.|||Required for the function of coenzyme Q in the respiratory chain. May serve as a chaperone or may be involved in the transport of Q6 from its site of synthesis to the catalytic sites of the respiratory complexes. http://togogenome.org/gene/10090:Pcyt1b ^@ http://purl.uniprot.org/uniprot/Q811Q9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytidylyltransferase family.|||Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis (PubMed:12842190). Plays an important role in ovary maturation and the maintenance of sperm production (PubMed:15143167).|||Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in brain (at protein level) (PubMed:12842190). Expressed at lower levels in lung and gonads (PubMed:15143167).|||Expression is low at 7 dpc, reaches a maximum at 15 dpc and decreases at 17 dpc.|||Female mice lacking isoform 1 have reduced fecundity due to failure in ovary maturation. Male mice lacking isoform 1 have reduced fecundity due to testicular degeneration.|||Highly expressed in brain (at protein level) (PubMed:12842190). Expressed in liver (at protein level) (PubMed:12842190). Expressed at lower levels in lung and gonads (PubMed:15143167).|||Homodimer.|||Not expressed in embryo. Expression starts at 5 weeks. http://togogenome.org/gene/10090:Pate14 ^@ http://purl.uniprot.org/uniprot/Q3UN54 ^@ Developmental Stage|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PATE family.|||By testosterone.|||Expressed from 3 weeks onwards.|||Glycosylated.|||Monomer.|||Predominantly expressed in the seminal vesicles (PubMed:16940290). Expressed in prostate, and to a lesser extent in the cauda epididymis (PubMed:21942998).|||Secreted http://togogenome.org/gene/10090:Stat6 ^@ http://purl.uniprot.org/uniprot/P52633 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transcription factor STAT family.|||Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling.|||Cytoplasm|||Forms a homodimer or a heterodimer with a related family member. Interacts with NCOA1 via its C-terminal LXXLL motif (By similarity).|||Mono-ADP-ribosylated by PARP14.|||Nucleus|||Tyrosine phosphorylated on Tyr-641 following stimulation by IL4/interleukin-4. Tyrosine phosphorylated following stimulation by IL3/interleukin-3. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates the IL4/interleukin-4 mediated signaling. http://togogenome.org/gene/10090:Timm10 ^@ http://purl.uniprot.org/uniprot/P62073 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small Tim family.|||Heterohexamer; composed of 3 copies of TIMM9 and 3 copies of TIMM10/TIM10A, named soluble 70 kDa complex. The complex forms a 6-bladed alpha-propeller structure and associates with the TIMM22 component of the TIM22 complex. Interacts with multi-pass transmembrane proteins in transit. Also forms a complex composed of TIMM9, TIMM10/TIM10A and FXC1/TIM10B (By similarity).|||Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity).|||Mitochondrion inner membrane|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). http://togogenome.org/gene/10090:Padi6 ^@ http://purl.uniprot.org/uniprot/Q8K3V4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein arginine deiminase family.|||Catalyzes the deimination of arginine residues of proteins (By similarity). In oocytes, is released during cortical reaction and plays a role in preimplantation cleavage and early embryonic development (PubMed:16137333). May be involved in cytoskeletal reorganization in the egg and early embryo (PubMed:17587491).|||Cortical granule|||Cytoplasm|||Detected in developing oocytes and early embryo. Detected in immature-germinal vesicle-stage oocytes, mature metaphase II arrested eggs and pronuclear zygotes, 2-cell, 4-cell and morula stages. Expression decreases in blastocyst stage.|||Expressed at very high levels in oocytes. Weakly expressed in testis. Expressed in primordial, primary, secondary and Graafian follicles, and in immature oocytes, mature eggs and blastocyst (at protein level).|||Knockout aninmals are viable and present at the expected Mendelian ratio. They do not exhibit any overt abnormalities. Female mice exhibit dispersal of the cytoskeletal sheets in oocytes that lead to a failure of zygotes to progress beyond the 2-cell stage and infertility (PubMed:17587491). Male fertility is not affected (PubMed:17587491).|||Nucleus|||Phosphorylation at Ser-2, possibly by RSK-type kinases, and Ser-434 creates binding sites for 14-3-3 proteins. http://togogenome.org/gene/10090:Vmn2r41 ^@ http://purl.uniprot.org/uniprot/E9Q5C7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Phf2 ^@ http://purl.uniprot.org/uniprot/Q9WTU0 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.|||Component of the PHF2-ARID5B complex, at least composed of PHF2 and ARID5B. Interacts with HNF4A and NR1H4 (By similarity). Interacts with RELA (PubMed:22921934).|||Enzymatically inactive by itself, and become active following phosphorylation by PKA.|||In contrast to the related histone demethylases JHDM1D and PHF8, the conserved active His in position 321 is replaced by a Tyr. However, the presence of a Tyr residue neither affects binding to the catalytic iron nor abolishes demethylase activity.|||Lysine demethylase that demethylates both histones and non-histone proteins (PubMed:22921934). Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA (By similarity). Involved in the activation of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the gene promoters (PubMed:22921934).|||Phosphorylated by PKA on specific serine residues, leading to the formation of an active lysine demethylase complex.|||The PHD-type zinc finger mediates the binding to H3K4me2 and H3K4me3.|||kinetochore|||nucleolus http://togogenome.org/gene/10090:Rsrc2 ^@ http://purl.uniprot.org/uniprot/A2RTL5 ^@ Similarity ^@ Belongs to the RSRC2 family. http://togogenome.org/gene/10090:Exo5 ^@ http://purl.uniprot.org/uniprot/Q9CXP9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EXO5 family.|||Binds 1 [4Fe-4S] cluster.|||Monomer; monomeric form has weak exonuclease activity. Homodimer; homodimeric form is unsure but has much higher exonuclease activity, suggesting that it could homodimerize upon DNA-binding. Interacts with the replication protein A (RPA) complex (By similarity).|||Nucleus|||Single-stranded DNA (ssDNA) bidirectional exonuclease involved in DNA repair. Probably involved in DNA repair following ultraviolet (UV) irradiation and interstrand cross-links (ICLs) damage. Has both 5'-3' and 3'-5' exonuclease activities with a strong preference for 5'-ends. Acts as a sliding exonuclease that loads at ssDNA ends and then slides along the ssDNA prior to cutting; however the sliding and the 3'-5' exonuclease activities are abolished upon binding to the replication protein A (RPA) complex that enforces 5'-directionality activity (By similarity).|||cytosol http://togogenome.org/gene/10090:Pif1 ^@ http://purl.uniprot.org/uniprot/Q80SX8 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. PIF1 subfamily.|||DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability. Efficiently unwinds G-quadruplex (G4) DNA structures and forked RNA-DNA hybrids. Resolves G4 structures, preventing replication pausing and double-strand breaks (DSBs) at G4 motifs. Involved in the maintenance of telomeric DNA. Inhibits telomere elongation, de novo telomere formation and telomere addition to DSBs via catalytic inhibition of telomerase. Reduces the processivity of telomerase by displacing active telomerase from DNA ends. Releases telomerase by unwinding the short telomerase RNA/telomeric DNA hybrid that is the intermediate in the telomerase reaction. Possesses an intrinsic strand annealing activity.|||Mice do not exhibit any change in telomere length in thymocytes or plenocytes nor significant change in chromosome gain or rearrangements.|||Mitochondrion|||Monomer (By similarity). Interacts with telomerase.|||Nucleus|||Produced by alternative initiation of isoform 1.|||The PIF1 N-terminal (PINT) domain enhances the interaction with ssDNA through intrinsic binding activity, it also harbors DNA strand-annealing activity. http://togogenome.org/gene/10090:Pwwp3b ^@ http://purl.uniprot.org/uniprot/Q4VA55 ^@ Similarity ^@ Belongs to the PWWP3A family. http://togogenome.org/gene/10090:Or2t49 ^@ http://purl.uniprot.org/uniprot/Q5NC44 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tma16 ^@ http://purl.uniprot.org/uniprot/Q9CR02 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with pre-60S ribosomal particles.|||Belongs to the TMA16 family.|||Involved in the biogenesis of the 60S ribosomal subunit in the nucleus.|||Nucleus http://togogenome.org/gene/10090:Hs6st2 ^@ http://purl.uniprot.org/uniprot/Q80UW0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.|||Belongs to the sulfotransferase 6 family.|||Membrane http://togogenome.org/gene/10090:Fuca1 ^@ http://purl.uniprot.org/uniprot/Q99LJ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.|||Belongs to the glycosyl hydrolase 29 family.|||Homotetramer.|||Lysosome http://togogenome.org/gene/10090:Nkx2-1 ^@ http://purl.uniprot.org/uniprot/P50220|||http://purl.uniprot.org/uniprot/Q6PFE0 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NK-2 homeobox family.|||Expressed in lung at least from to 9.5 dpc to adulthood.|||Interacts with WWTR1.|||Nucleus|||Phosphorylated on serine residues by STK3/MST2.|||Thyroid, lung and brain.|||Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis. Forms a regulatory loop with GRHL2 that coordinates lung epithelial cell morphogenesis and differentiation (PubMed:22955271). Activates the transcription of GNRHR and plays a role in enhancing the circadian oscillation of its gene expression. Represses the transcription of the circadian transcriptional repressor NR1D1 (PubMed:22356123). http://togogenome.org/gene/10090:Rbp3 ^@ http://purl.uniprot.org/uniprot/P49194 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S41A family.|||Expressed in the photosensitive tissues; retina and pineal gland.|||IRBP shuttles 11-cis and all trans retinoids between the retinol isomerase in the pigment epithelium and the visual pigments in the photoreceptor cells of the retina.|||interphotoreceptor matrix http://togogenome.org/gene/10090:Kif23 ^@ http://purl.uniprot.org/uniprot/E9Q5G3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Essential for cytokinesis in Rho-mediated signaling. Required for the localization of ECT2 to the central spindle. Plus-end-directed motor enzyme that moves antiparallel microtubules in vitro (By similarity).|||Detected in testis and ovary from newborn mice (at protein level). Detected in brain, spinal cord and small intestine.|||Heterotetramer of two molecules each of RACGAP1 and KIF23. Found in the centralspindlin complex. Interacts with RACGAP1; the interaction is direct. Interacts with ECT2 and PRC1. Interacts with ANXA11 during cytokinesis. Interacts with BIRC6/bruce and USP8/UBPY (By similarity). Interacts with ARF6, forming heterodimers and heterotetramers.|||Midbody ring|||Nucleus|||Ubiquitinated. Deubiquitinated by USP8/UBPY (By similarity).|||spindle http://togogenome.org/gene/10090:Gsdma3 ^@ http://purl.uniprot.org/uniprot/A0A679AUV5|||http://purl.uniprot.org/uniprot/Q5Y4Y6 ^@ Activity Regulation|||Biotechnology|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A3, N-terminal) that initiates pyroptosis (By similarity). In contrast to Gsdma, not cleaved by bacterial effector protein SpeB (PubMed:35110732).|||Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane (PubMed:33883744). The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744).|||Highest levels in skin with weak expression in placenta and testis. Not detected in the gastrointestinal tract. In skin, expressed in postnatal hair follicles and epidermis as well as sebaceous gland basal cells.|||Homooligomer; homooligomeric ring-shaped pore complex containing 18-36 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal (PubMed:26375003). The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain (PubMed:26375003).|||Membrane|||Mitochondrion membrane|||No visible phenotype (PubMed:25825937). A number of gain-of-function mutations, such as alopecia and excoriation (AE), bareskin (Bsk), defolliculated (Dfl), finnegan (Fgn) reduced coat 2 (Rco2), Rex-denuded (Re-den) and recombination induced mutation 3 (Rim3), have been identified: they cause progressive hair loss (alopecia) accompanied with hyperkeratosis and chronic skin inflammation (PubMed:15475261, PubMed:15737203, PubMed:17572385, PubMed:22155111). Gain-of-function mutations cause bulge stem cell depletion, leading to skin inflammation and alopecia (PubMed:22155111). Mice lacking Gsdma, Gsdma2 and Gsdma3 are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model (PubMed:35545676).|||Not detected at postnatal day 1. Expressed on subsequent postnatal days up to day 20 and throughout adulthood.|||Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:26375003, PubMed:27281216, PubMed:35545613). Released upon cleavage by some bacterial effector protein, and binds to membrane inner leaflet lipids (By similarity). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukin-1 (IL1B and IL18) and triggering pyroptosis (PubMed:27281216, PubMed:33883744, PubMed:35545613). Binds to membrane inner leaflet lipids, including bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to monophosphorylated phosphatidylinositols (PubMed:27281216). Also binds to bacterial and mitochondrial lipids, including cardiolipin, and exhibits bactericidal activity (PubMed:27281216, PubMed:29695864). Plays a role in the transition from catagen to telogen at the end of hair follicle morphogenesis, possibly by regulating hair follicle stem cell niche maintenance (PubMed:15475261, PubMed:15737203, PubMed:17572385, PubMed:22155111, PubMed:32302611). Also required for mammary gland development (PubMed:28168650).|||Precursor of a pore-forming protein involved in the transition from catagen to telogen at the end of hair follicle morphogenesis (PubMed:15475261, PubMed:26375003, PubMed:27281216). This form constitutes the precursor of the pore: upon cleavage, the released N-terminal moiety (Gasdermin-A3, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:26375003, PubMed:27281216, PubMed:35545613). This form acts as a sensor of infection: activation is triggered by cleavage by some bacterial effector protein, which releases the N-terminal moiety (Gasdermin-A3, N-terminal) (By similarity).|||Pyroptosis-induced inflammation mediated by Gsdma3 triggers robust anti-tumor immunity and may be used in therapies to suppress tumor growth (PubMed:32188939). Use of a nanoparticle-mediated delivery system that selectively directs release of N-terminal moiety (Gasdermin-A3, N-terminal) into tumor cells, triggers pyroptosis and robust anti-tumor immunity (PubMed:32188939). Pyroptosis of less than 15% of tumor cells is sufficient to clear the entire tumor in a mammary tumor graft (PubMed:32188939).|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:25825937, PubMed:26100518, PubMed:26375003). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A3, N-terminal) (PubMed:26100518, PubMed:26375003).|||cytosol http://togogenome.org/gene/10090:Rgma ^@ http://purl.uniprot.org/uniprot/Q6PCX7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds.|||Belongs to the repulsive guidance molecule (RGM) family.|||Cell membrane|||Expressed in gradient in periventricular layers of the developing nervous system. In adult, expressed in scattered cells throughout the brain.|||Expressed in the early developing nervous system, with the exception of prominent gaps in the mid-hindbrain and the fore-midbrain boundaries. By 10.5 dpc, expression in the nervous system decreases slightly and a segmented pattern of expression appears, marking the ventral sites of somitic buds. At that stage, the expression shows a strong dorsal to ventral gradient. In the neural tubes, strong expression is detected at the level of the floor plate and in the medial portion of the neural tubes. Lower expression is detected in the dorsal neural tube and the ventral aspect corresponding to the area of motoneuron differentiation. In the developing eye, expressed in the perioptic mesenchyme.|||Interacts with NEO1, BMP2 and BMP4.|||Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8. http://togogenome.org/gene/10090:Zfp879 ^@ http://purl.uniprot.org/uniprot/Q8BI99 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Oaz3 ^@ http://purl.uniprot.org/uniprot/Q9R109 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ODC antizyme family.|||Cytoplasm|||Expression starts early in spermiogenesis and finishes in the late spermatid phase.|||Interacts with ODC1 and thereby sterically blocks ODC homodimerization (By similarity). Interacts with AZIN2; this interaction disrupts the interaction between the antizyme and ODC1 (PubMed:16916800, PubMed:18062773, PubMed:18973822). Interacts with GGN (PubMed:15642376).|||Nucleus|||Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity (PubMed:16916800, PubMed:18508777, PubMed:18973822). Stabilizes AZIN2 by interfering with its ubiquitination (PubMed:18062773). Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol (PubMed:19449338). Probably plays a key role in spermatogenesis by regulating the intracellular concentration of polyamines in haploid germ cells (PubMed:24967154).|||Testis specific. Expressed throughout the differentiation process from spermatids to spermatozoa in the inner part of the seminiferous tubules.|||Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon. http://togogenome.org/gene/10090:Deptor ^@ http://purl.uniprot.org/uniprot/Q570Y9 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Associated component of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR. Associated component of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PROTOR1, RICTOR, MAPKAP1 and DEPTOR. Interacts (via PDZ domain) with MTOR; interacts with MTOR within both mTORC1 and mTORC2. Interacts (via PDZ domain) with MINAR1 (via N-terminus). Interacts with SIK3.|||At postnatal day 1 (P1), in cartilage growth plate, primarily expressed in resting and proliferating chondrocytes. This expression pattern is maintained at least until P21 (at protein level).|||Inhibited upon phosphatidic acid-binding: phosphatidic acid produced upon mitogenic stimulation promotes DEPTOR dissociatiom from the mTORC1 and mTORC2 complexes, leading to their activation. Specifically binds unsaturated phosphatidic acid, such as 16:0-18:1, 18:0-18:1 and di-18:1. Inhibited when nutrients are present via a feedback loop: phosphorylation by MTOR promotes DEPTOR ubiquitination and degradation.|||Lysosome membrane|||Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes. DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy. In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity.|||Phosphorylation weakens interaction with MTOR within mTORC1 and mTORC2 (By similarity). Phosphorylated at Ser-286, Ser-287 and Ser-291 in response to mitogenic stimulation by MTOR: DEPTOR is either directly phosphorylated by MTOR or indirectly via proteins kinases that are activated by MTOR, such as CK1/CSNK1A1 (By similarity). Phosphorylation at Ser-286, Ser-287 and Ser-291 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (By similarity). Phosphorylation at Ser-235 by MAPK3/ERK1 promotes deubiquitination by USP7, enhancing its stability (By similarity). Phosphorylation at Tyr-291 by SYK impairs its interaction with MTOR, promoting mTORC1 and mTORC2 signaling (By similarity).|||Ubiquitinated; leading to proteasomal degradation (By similarity). Ubiquitination by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-286, Ser-287 and Ser-291 by MTOR, leads to its degradation by the proteasome (By similarity). Deubiquitinated by OTUB1 in response to amino acid via a non-canonical mechanism, leading to DEPTOR stability (By similarity). Deubiquitinated by USP7 following phosphorylation at Ser-235, promoting its stability (By similarity). http://togogenome.org/gene/10090:Phyh ^@ http://purl.uniprot.org/uniprot/O35386 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PhyH family.|||Catalyzes the 2-hydroxylation of not only racemic phytanoyl-CoA and the isomers of 3-methylhexadecanoyl-CoA, but also a variety of other mono-branched 3-methylacyl-CoA esters (with a chain length of at least seven carbon atoms) and straight-chain acyl-CoA esters (with a chain length longer than four carbon atoms) (By similarity). Does not hydroxylate long and very long straight chain acyl-CoAs or 2-methyl-and 4-methyl-branched acyl-CoAs (By similarity).|||Defects in Phyh are the cause of lupus nephritis, a severe autoimmune disease. Phyh could be involved in a reaction against the progression of the disease, because its expression is low in the early stage of the disease in the renal cortex of MRL/lpr mice.|||Interacts with FKBP52 (By similarity). Interacts with PHYHIP (PubMed:10686344).|||Peroxisome|||Ubiquitously expressed in all tissues with significant levels detected in the embryonic and neonatal heart and liver. In the adult, significant levels are detected in the liver, kidney, heart, gut, brain and aorta. http://togogenome.org/gene/10090:Or8k40 ^@ http://purl.uniprot.org/uniprot/Q8VGA6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gnmt ^@ http://purl.uniprot.org/uniprot/Q9QXF8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.|||Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy), a reaction regulated by the binding of 5-methyltetrahydrofolate (PubMed:15340920). Plays an important role in the regulation of methyl group metabolism by regulating the ratio between S-adenosyl-L-methionine and S-adenosyl-L-homocysteine (PubMed:16779654).|||Cytoplasm|||Deficient mice are fertile and display elevated levels of methionine and S-adenosylmethionine in the liver. At 3 and 8 months of age, the livers at 3 and 8 months of age show evidence of fatty accumulation and fibrosis that worsen progressively.|||Homotetramer.|||Inhibited by 5-methyltetrahydrofolate monoglutamate and by 5-methyltetrahydrofolate pentaglutamate, inhibition is much more effective by the pentaglutamate form than by the monoglutamate form. Two molecules of 5-methyltetrahydrofolate are bound per tetramer. The binding sites are localized between subunits. Inhibitor binding may preclude movements of the polypeptide chain that are necessary for enzyme activity. http://togogenome.org/gene/10090:Bid ^@ http://purl.uniprot.org/uniprot/P70444 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein BCL2 (PubMed:21183079). Interacts with PLEKHN1 (By similarity).|||Induces caspase activation and apoptosis (By similarity). Allows the release of cytochrome c (PubMed:9873064).|||Induces caspases and apoptosis. Counters the protective effect of BCL2.|||Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family. Apoptotic members of the Bcl-2 family.|||Interacts with ITCH (PubMed:20392206). Interacts with MTCH2 (PubMed:15899861).|||Mitochondrion membrane|||Mitochondrion outer membrane|||TNF-alpha induces caspase-mediated cleavage into a major p15 and minor p13 and p11 products (PubMed:9873064). Cleaved by CASP6 into a major p15 and minor p13 products, leading to release of cytochrome c and subsequent nonalcoholic steatohepatitis (By similarity).|||Ubiquitinated by ITCH; ubiquitination results in proteasome-dependent degradation. http://togogenome.org/gene/10090:Fbln7 ^@ http://purl.uniprot.org/uniprot/Q501P1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An adhesion molecule that interacts with extracellular matrix molecules in developing teeth and may play important roles in differentiation and maintenance of odontoblasts as well as in dentin formation.|||Belongs to the fibulin family.|||Expressed by preodontoblasts and odontoblasts in developing teeth. Localizes to the apical pericellular regions of preodontoblasts. When the dentin matrix is fully formed and dentin mineralization occurs, it is present in the predentin matrix and along the dentinal tubules. It is also expressed in the developing growth plate cartilage, hair follicles and extraembryonic areas of the placenta.|||Highly expressed in newborn incisors and molars. A weaker expression is seen in the brain, kidneys, muscles and bones.|||Interacts with heparin, FBLN1, FN1 and DSPP. Preferentially binds dental mesenchyme cells and odontoblasts but not dental epithelial cells or nondental cells. Binding requires a heparan sulfate-containing receptor on the cell surface as well as an integrin.|||N-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:H2al1i ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:Or6c69 ^@ http://purl.uniprot.org/uniprot/Q8VFU2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dctn3 ^@ http://purl.uniprot.org/uniprot/Q9Z0Y1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynactin subunit 3 family.|||Cleavage furrow|||Cytoplasm|||Midbody|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Together with dynein may be involved in spindle assembly and cytokinesis (By similarity).|||Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin.|||centrosome|||kinetochore|||spindle http://togogenome.org/gene/10090:Uchl4 ^@ http://purl.uniprot.org/uniprot/B2RTM4|||http://purl.uniprot.org/uniprot/P58321 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C12 family.|||Cytoplasm|||Expressed in various tissues at low level.|||Ubiquitin-protein hydrolase is involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. http://togogenome.org/gene/10090:Slc35f3 ^@ http://purl.uniprot.org/uniprot/Q1LZI2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC35F solute transporter family.|||Mediates thiamine transport.|||Membrane http://togogenome.org/gene/10090:Ripk2 ^@ http://purl.uniprot.org/uniprot/P58801|||http://purl.uniprot.org/uniprot/Q547H1 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated (PubMed:19473975). Phosphorylated at Ser-176, either via autophosphorylation or by LRRK2, enhancing activity (PubMed:19473975). Autophosphorylation at Tyr-473 is required for effective NOD2 signaling (By similarity). Autophosphorylation is however not essential for NOD2 signaling (By similarity).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cell membrane|||Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins.|||Cytoplasm|||Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes NOD1/NOD2-RIPK2 RIPosome recruitment to autophagosome membranes. RIPK2 biquitinated via 'Lys-63'-linked chains is then recognized by SQSTM1/p62, leading to the SQSTM1/p62-dependent autophagic degradation of the NOD1/NOD2-RIPK2 RIPosome.|||Endoplasmic reticulum|||Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2.|||In the inactive state, the helix alphaC is packed against the helical, non-phosphorylated activation segment (AS). Upon activation, helix alphaC is displaced and the phosphorylated AS becomes disordered.|||Interacts (via CARD domain) with NOD2 (via CARD domain) (By similarity). Interacts (via CARD domain) with NOD1 (via CARD domain) (By similarity). Homooligomer; following interaction with NOD1 or NOD2, homooligomerizes via its CARD domain and forms long filaments named RIPosomes (By similarity). Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2 (By similarity). Interacts with ARHGEF2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK (By similarity). Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway (By similarity). Interacts with IKBKG/NEMO (By similarity). The polyubiquitinated protein interacts with MAP3K7/TAK1; interaction is indirect and is mediated by TAB2 and TAB3 that bind to polyubiquitin chains attached to RIPK2 (By similarity). Binds to CFLAR/CLARP and CASP1 via their CARD domains (By similarity). Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6 (By similarity). Interacts with NLRP10 (By similarity). Interacts with CARD9 (PubMed:17187069). Interacts with INAVA; the interaction takes place upon PRR stimulation (By similarity). Interacts (via CARD domain) with NGFR (via death domain) (By similarity). Interacts with Irgm1; promoting RIPK2 degradation (By similarity).|||Mice show a lack of chemokine production induced by bacterial peptidoglycans. RIPK2 deficiency affects cellular signaling and cytokine responses triggered by NOD1 and NOD2 ligands, but not TLR ligands.|||Polyubiquitinated via both 'Lys-63'- and 'Met-1'-linked polyubiquitin following recruitment by NOD1 or NOD2, creating docking sites for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling (PubMed:17947236). 'Lys-63'-linked polyubiquitination by XIAP is essential for NOD2 signaling and promotes recruitment of the LUBAC complex (By similarity). Also polyubiquitinated with 'Lys-63'-linked chains by PELI3, BIRC2/c-IAP1 and BIRC3/c-IAP2 (PubMed:23892723). Ubiquitinated on Lys-209 via 'Lys-63'-linked by ITCH (By similarity). Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to attenuate NOD2-mediated inflammation and tissue damage (PubMed:30405132). Polyubiquitinated with 'Lys-63'-linked chains in response to Shigella infection, promoting its SQSTM1/p62-dependent autophagic degradation (By similarity). Undergoes 'Met-1'-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation 'Met-1'-linked polyubiquitination (By similarity). 'Lys-63'-linked polyubiquitination by XIAP is required for recruimtent of the LUBAC complex and subsequent (By similarity). Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent pro-inflammatory signaling activation of NF-kappa-B (By similarity). Ubiquitination at Lys-502 by ZNRF4 via 'Lys-48'-linked polyubiquitination promotes RIPK2 degradation by the proteasome; ubiquitination by ZNRF4 takes place during both acute and NOD2 tolerance conditions (By similarity).|||Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (By similarity). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17277144, PubMed:21469090, PubMed:30405132). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:30405132). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (By similarity). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:17965022). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (By similarity). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (By similarity). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (By similarity). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (By similarity). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181).|||Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses. Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments.|||The role of autophosphorylation in RIPK2 activation is unclear: an initial studies suggested that autophosphorylation is essential to activate NOD2 signaling pathway (PubMed:19473975). However, it was later shown that autophosphorylation is however not essential for NOD2 signaling (By similarity). http://togogenome.org/gene/10090:Mlx ^@ http://purl.uniprot.org/uniprot/O08609 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAD1, MAD4, MNT, WBSCR14 and MLXIP. Can also bind DNA as a homodimer.|||Expressed in all tissues examined: stomach, duodenum, jejunum, ileum, colon, liver, pancreas, salivary gland, kidney, spleen, lung, heart, skeletal muscle, brain, ovary and testis.|||Expression peaks between dpc 9.5 to 11.5, then decreases during later stages of organogenesis.|||Nucleus|||Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MAD1, MAD4, MNT, WBSCR14 and MLXIP which recognizes the core sequence 5'-CACGTG-3'. The TCFL4-MAD1, TCFL4-MAD4, TCFL4-WBSCR14 complexes are transcriptional repressors. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation. http://togogenome.org/gene/10090:Lyrm7 ^@ http://purl.uniprot.org/uniprot/Q9DA03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Assembly factor required for Rieske Fe-S protein UQCRFS1 incorporation into the cytochrome b-c1 (CIII) complex. Functions as a chaperone, binding to this subunit within the mitochondrial matrix and stabilizing it prior to its translocation and insertion into the late CIII dimeric intermediate within the mitochondrial inner membrane (By similarity).|||Belongs to the complex I LYR family.|||Interacts with UQCRFS1.|||Mitochondrion matrix http://togogenome.org/gene/10090:Plce1 ^@ http://purl.uniprot.org/uniprot/Q8K4S1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs (By similarity).|||Cell membrane|||Golgi apparatus membrane|||Highly expressed in neurons and to a lower extent in skin, skeletal muscle and heart (at protein level). Expressed in the epidermis.|||Interacts with RHOA (By similarity). Interacts with IQGAP1, HRAS, RAP1A, RAP2A, RAP2B and RRAS (By similarity). Interacts with IQGAP1 (PubMed:17086182). Interacts with AVIL (By similarity).|||Mice exhibit delayed onset and markedly reduced incidence of chemically induced skin squamous tumors. They also display cardiac malformations which mainly affects aortic and pulmonary valves and enhanced susceptibility to cardiac hypertrophy and fibrosis in response to chronic stress.|||Probable cloning artifact.|||Specifically expressed in cells committed to the neuronal lineage (at protein level). Weakly expressed at 7 dpc, expression strongly increases at later embryonic stages. Expressed abundantly in almost all neural tissues at 12.5 dpc and also detected in tongue muscles, genital tubercle and hand plate. At 15.5 dpc a strong expression in skeletal muscles is detected together with the strong expression in neural tissues.|||The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway (By similarity).|||The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell membrane (By similarity).|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (By similarity).|||Up-regulated during the differentiation of neural precursor cells into neurons but not glial cells. Up-regulated in heart upon induced hypertrophy.|||cytosol|||lamellipodium http://togogenome.org/gene/10090:Tsnaxip1 ^@ http://purl.uniprot.org/uniprot/Q99P25 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with TSNAX.|||Possible role in spermatogenesis.|||Specifically expressed in testes. Predominantly detected in the post-meiotic stages of germ cells.|||perinuclear region http://togogenome.org/gene/10090:Or5b104 ^@ http://purl.uniprot.org/uniprot/Q8VFK3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp20a1 ^@ http://purl.uniprot.org/uniprot/Q80Y48|||http://purl.uniprot.org/uniprot/Q8BKE6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Membrane http://togogenome.org/gene/10090:Acad9 ^@ http://purl.uniprot.org/uniprot/Q8JZN5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the MCIA complex, primarily participates in the assembly of the mitochondrial complex I and therefore plays a role in oxidative phosphorylation. This moonlighting protein has also a dehydrogenase activity toward a broad range of substrates with greater specificity for long-chain unsaturated acyl-CoAs. However, in vivo, it does not seem to play a primary role in fatty acid oxidation. In addition, the function in complex I assembly is independent of the dehydrogenase activity of the protein.|||Belongs to the acyl-CoA dehydrogenase family.|||Homodimer (By similarity). Interacts with NDUFAF1 and ECSIT (By similarity). Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 (By similarity). Interacts with TMEM70 and TMEM242 (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Vmn1r75 ^@ http://purl.uniprot.org/uniprot/Q8R289 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Rhbdf1 ^@ http://purl.uniprot.org/uniprot/Q6PIX5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S54 family.|||Endoplasmic reticulum membrane|||Expressed in the duodenum, as well as in fetal liver and head.|||Golgi apparatus membrane|||Homodimer, or homooligomer. Interacts with TGFA and HBEGF (By similarity). Interacts with EGF; may retain EGF in the endoplasmic reticulum and regulates its degradation through the endoplasmic reticulum-associated degradation (ERAD) (PubMed:21439629). Interacts (via cytoplasmic N-terminus) with FRMD8/iTAP; this interaction leads to mutual protein stabilization (By similarity). Interacts with ADAM17/TACE (By similarity).|||Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. http://togogenome.org/gene/10090:Dmrtc1b ^@ http://purl.uniprot.org/uniprot/A2AI93|||http://purl.uniprot.org/uniprot/Q2PMX6|||http://purl.uniprot.org/uniprot/Q2PMX7 ^@ Similarity ^@ Belongs to the DMRT family. http://togogenome.org/gene/10090:Kalrn ^@ http://purl.uniprot.org/uniprot/A2CG49|||http://purl.uniprot.org/uniprot/D3Z4R2 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Interacts with the C-terminal of peptidylglycine alpha-amidating monooxygenase (PAM) and with the huntingtin-associated protein 1 (HAP1). Interacts with FASLG (By similarity).|||Produced by alternative initiation at Met-624 of isoform 1. Inferred by similarity.|||Produced by alternative splicing.|||Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity (By similarity).|||The two GEF domains catalyze nucleotide exchange for RAC1 and RhoA which are bound by DH1 and DH2 respectively. The two GEF domains appear to play differing roles in neuronal development and axonal outgrowth. SH3 1 binds to the first GEF domain inhibiting GEF activity only when in the presence of a PXXP peptide, suggesting that the SH3 domain/peptide interaction mediates binding to GEF1. CRK1 SH3 domain binds to and inhibits GEF1 activity (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Ipo5 ^@ http://purl.uniprot.org/uniprot/Q8BKC5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the importin beta family. Importin beta-3 subfamily.|||Cytoplasm|||Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. Binds to CPEB3 and mediates its nuclear import following neuronal stimulation (PubMed:22730302).|||Interacts with RPS7 and RPL5 (By similarity). Directly interacts with RPL23A (via BIB domain) (By similarity). Interacts with H2A, H2B, H3 and H4 histones (PubMed:11493596). Interacts with CPEB3; this mediates CPEB3 nuclear import following neuronal stimulation which enhances the interaction in a RAN-regulated manner (By similarity). Interacts with AIFM2; this interaction likely mediates the translocation of AIFM2 into the nucleus upon oxidative stress (By similarity). Interacts with STX3 (isoform 3) (PubMed:26689472). Interacts with SRP19 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Hck ^@ http://purl.uniprot.org/uniprot/P08103 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Expressed predominantly in cells of the myeloid and B-lymphoid lineages.|||Golgi apparatus|||Initiates from a CTG codon.|||Interacts with ADAM15. Interacts with FASLG. Interacts with ARRB1 and ARRB2. Interacts with FCGR1A; the interaction may be indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1. Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1 (By similarity). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1. Interacts (via SH3 domain) with WDCP (By similarity).|||Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.|||Lysosome|||Membrane|||No visible phenotype, but macrophages have impaired phagocytosis. Mice lacking both HCK and FGR are extremely sensitive to infections by L.monocytogenes.|||Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS (By similarity).|||Nucleus|||Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-409 increases kinase activity. Phosphorylation at Tyr-520 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-520, suggesting that this site may be a target of other kinases.|||Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity. Inhibited by PP1.|||Ubiquitinated by CBL, leading to its degradation via the proteasome.|||Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.|||caveola|||cytoskeleton|||cytosol|||focal adhesion|||podosome membrane|||secretory vesicle http://togogenome.org/gene/10090:Cyp7a1 ^@ http://purl.uniprot.org/uniprot/Q64505 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols) (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (By similarity). Functions as a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis. Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol, a rate-limiting step in cholesterol catabolism and bile acid biosynthesis (Probable). 7-alpha hydroxylates several oxysterols, including 4beta-hydroxycholesterol and 24-hydroxycholesterol. Catalyzes the oxidation of the 7,8 double bond of 7-dehydrocholesterol and lathosterol with direct and predominant formation of the 7-keto derivatives (By similarity).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane|||Up-regulated by fasting, returns to ground state upon feeding. Up-regulated by experimentally induced diabetes. Down-regulated by insulin treatment. http://togogenome.org/gene/10090:Cttnbp2nl ^@ http://purl.uniprot.org/uniprot/Q99LJ0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ May form homomers (By similarity). May interact with MOB4, PPP2R1A, PPP2CB, STK24, STK25, STK26, STRN4, STRIP1 and STRIP2 (By similarity). Interacts with CTTN/cortactin; this interaction may redistribute CTTN to stress fibers.|||Predominantly expressed in skin, also detectable in spleen and lung (at protein level). Very low levels, if any, in brain (at protein level).|||Regulates lamellipodial actin dynamics in a CTTN-dependent manner.|||lamellipodium|||stress fiber http://togogenome.org/gene/10090:Trex2 ^@ http://purl.uniprot.org/uniprot/Q3SXB3|||http://purl.uniprot.org/uniprot/Q9R1A9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the exonuclease superfamily. TREX family.|||Binds 2 Mg(2+) per subunit. The second magnesium ion interacts with only one residue. Substitution with Mn(2+) results in partial activity.|||Exonuclease with a preference for double-stranded DNA with mismatched 3' termini. May play a role in DNA repair.|||Homodimer.|||Nucleus http://togogenome.org/gene/10090:Cfi ^@ http://purl.uniprot.org/uniprot/Q61129 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||CFI-deficient mice are viable and fertile under specific pathogen-free conditions. In the absence of factor I/CFI, physiological cleavage of the alpha-chain of C3b is prevented, and reduced plasma C3, factor B, and factor H levels are observed.|||Expressed in the liver by hepatocytes. Also present in other cells such as monocytes, fibroblasts or keratinocytes.|||Heterodimer of a light and heavy chains; disulfide-linked. The fully processed and mature protein circulates as a zymogen, and is allosterically activated by substrate-induced remodeling of the active site. Interacts with C3b. Interacts with complement factor H.|||Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 on cell surfaces. The presence of these cofactors on healthy cells allows degradation of deposited C3b by CFI in order to prevent undesired complement activation, while in apoptotic cells or microbes, the absence of such cofactors leads to C3b-mediated complement activation and subsequent opsonization.|||extracellular space http://togogenome.org/gene/10090:Gdap2 ^@ http://purl.uniprot.org/uniprot/Q9DBL2 ^@ Developmental Stage|||Induction|||Similarity|||Tissue Specificity ^@ Belongs to the GDAP2 family.|||By differentiation in neurons.|||Expressed at high levels in brain and testis, and at low levels in liver and kidney.|||In the brain, expression starts at 12 dpc and increases until adulthood. http://togogenome.org/gene/10090:Tmprss11g ^@ http://purl.uniprot.org/uniprot/Q8BZ10 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Membrane http://togogenome.org/gene/10090:Sin3a ^@ http://purl.uniprot.org/uniprot/Q60520 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (PubMed:22476904). Required for cortical neuron differentiation and callosal axon elongation (PubMed:27399968).|||Contaminating sequence. Potential poly-A sequence.|||Interacts with ARID4B, BRMS1L, HCFC1, HDAC1, HDAC2, MXI1, SAP30L, SAP130, SFPQ and TOPORS (PubMed:8649810). Interacts with OGT (via TPRs 1-6); the interaction mediates transcriptional repression in parallel with histone deacetylase (By similarity). Interacts with BAZ2A, MXD1, MXD3, MXD4, MBD2, DACH1, NCOR1, NR4A2, REST, RLIM, SAP30, SETDB1, SMYD2, and SUDS3 (PubMed:7889570, PubMed:8521822, PubMed:9139820, PubMed:9702189, PubMed:10734093, PubMed:10950960, PubMed:11106735, PubMed:11882901, PubMed:11909966, PubMed:12130660, PubMed:12198165, PubMed:12398767, PubMed:16805913, PubMed:19144721). Interacts with PHF12 in a complex composed of HDAC1, PHF12 and SAP30 (PubMed:11390640). Interacts with TET1; the interaction recruits SIN3A to gene promoters (PubMed:21490601). The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A (PubMed:21680841). Interacts with KLF11 (PubMed:15774581). Interacts with PPHLN1 (By similarity). Found in a complex with YY1, GON4L and HDAC1 (PubMed:21454521). Interacts (via PAH2) with FOXK1 (PubMed:22476904, PubMed:25402684). Interacts with FOXK2 (PubMed:25402684). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (PubMed:28554894). Interacts with SINHCAF (PubMed:28554894). Interacts with SPHK2 (By similarity).|||Nucleus|||Probable cloning artifact leading to an internal deletion.|||SIN3A knockdown causes a significant decrease in the amount of cortical progenitors in the proliferative zone at the peak of neurogenesis, and results in altered neuronal identity and aberrant corticocortical projections.|||SUMO1 sumoylated by TOPORS. Probably desumoylated by SENP2.|||The cDNA contains an internal 15bp tandem duplication.|||Widely expressed. Highest levels in testis, lung and thymus. Expressed at relatively high levels throughout brain development. In adult mice, expression is high in neurogenic regions such as the subventricular zone, rostral migratory stream, olfactory bulb and dentate gyrus (PubMed:27399968).|||nucleolus http://togogenome.org/gene/10090:Pabpc1 ^@ http://purl.uniprot.org/uniprot/P29341 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the polyadenylate-binding protein type-1 family.|||Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability. Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs. Involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability.|||Cytoplasm|||May form homodimers. Component of a multisubunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Directly interacts with IGF2BP1. Part of a complex associated with the FOS mCRD domain and consisting of HNRPD, SYNCRIP, PAIP1 and CSDE1/UNR. Interacts with PAIP1 and PAIP2 (via the PABPC1-interacting motifs PAM1 and PAM2). Interacts with PAIP1 with a 1:1 stoichiometry and with PAIP2 with a 1:2 stoichiometry (By similarity). The interaction with CSDE1 is direct and RNA-independent (PubMed:15314026). Found in a mRNP complex with YBX2 (PubMed:10076007). Interacts with TENT2/GLD2 (PubMed:17927953). Identified in the spliceosome C complex. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. The interaction with DDX3X is direct and RNA-independent. This interaction increases in stressed cells and decreases during cell recovery. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with NXF1/TAP (By similarity). Interacts with PIWIL1 (PubMed:19020299). Interacts with AGO1, AGO2, GSPT1 and GSPT2. Interacts with LARP4B. Interacts (via the second and third RRM domains and the C-terminus) with PAIP2B (via central acidic portion and C-terminus). Forms a complex with LARP1 and SHFL. Interacts with LARP4. Interacts with ZFC3H1 in a RNase-sensitive manner. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner. Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function. Interacts with G3BP1 and G3BP2 (By similarity). Interacts with ENDOV; the interaction is RNA-dependent and stimulates ENDOV activity (By similarity). Interacts with UPF1; the interaction is RNA-dependent (By similarity). Interacts with IGF2BP2 and IGF2BP3. May interact with SETX. Interacts with RBM46 (PubMed:36001654). Interacts with PAN3 isoform 1/Pan3L and isoform 3/Pan3S (via N-terminus); interaction with isoform 1 is less efficient than with isoform 3 (By similarity).|||Methylated by CARM1. Arg-493 is dimethylated, probably to asymmetric dimethylarginine (By similarity).|||Nucleus|||Phosphorylated by MAPKAPK2.|||Stress granule|||The RNA-binding domains RRM1 and RRM2 and the C-terminus (last 138 amino acids) regions interact respectively with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP1, respectively.|||The RNA-binding domains RRM2 and RRM3 and the C-terminus (last 138 amino acids) regions interact with the PABPC1-interacting motif-1 (PAM1) and -2 (PAM2) of PAIP2, respectively.|||lamellipodium http://togogenome.org/gene/10090:Lypd4 ^@ http://purl.uniprot.org/uniprot/Q8BVP6 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Or2n1c ^@ http://purl.uniprot.org/uniprot/Q8VEY4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp786 ^@ http://purl.uniprot.org/uniprot/Q8BV42 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Idh3a ^@ http://purl.uniprot.org/uniprot/Q9D6R2 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the isocitrate and isopropylmalate dehydrogenases family.|||Catalytic subunit of the enzyme which catalyzes the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal activity but the full activity of the heterotetramer (containing two subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly and cooperative function of both heterodimers.|||Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) ion per subunit.|||Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.|||IDH3A-null homozygous mice do not survive early embryogenesis (PubMed:30478029). Compound heterozygous mice for the IDH3A-null allele and mutant p.E229K are viable and exhibit rapid retinal degeneration (PubMed:30478029).|||Mitochondrion|||The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits. http://togogenome.org/gene/10090:Slc35b1 ^@ http://purl.uniprot.org/uniprot/P97858 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ ATP:ADP antiporter that catalyzes the exchange of ATP and ADP across the endoplasmic reticulum (ER) membrane. Imports ATP from the cytosol to the ER lumen and exports ADP in the opposite direction. Regulates ER energy metabolism and protein biogenesis. Appears to be part of a calcium-dependent ER to cytosol low energy response axis, where calcium efflux from ER to the cytosol triggers ATP import into the ER lumen to maintain sufficient ATP supply. Provides ATP to ER chaperone HSPA5 that drives protein folding and trafficking in the ER. Can transport dATP, UTP or UDP in exchange for ATP, but the physiological relevance of this process remains to be established.|||Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.|||Endoplasmic reticulum membrane|||The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins. http://togogenome.org/gene/10090:Fam20b ^@ http://purl.uniprot.org/uniprot/Q8VCS3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAM20 family.|||Embryos show severe stunting and increased mortality at 13.5 dpc.|||Golgi apparatus membrane|||Little expression detected in the secretory stage enamel. Weak to moderate expression is observed in the gingivae and odontoblasts. Strong expression in maturation stage ameloblasts.|||Responsible for the 2-O-phosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature GAG chains. Sulfated glycosaminoglycans (GAGs), including heparan sulfate and chondroitin sulfate, are synthesized on the so-called common GAG-protein linkage region (GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser) of core proteins, which is formed by the stepwise addition of monosaccharide residues by the respective specific glycosyltransferases. Xylose 2-O-phosphorylation may influence the catalytic activity of B3GAT3 (GlcAT-I) which completes the precursor tetrasaccharide of GAG-protein linkage regions on which the repeating disaccharide region is synthesized. http://togogenome.org/gene/10090:Fam117a ^@ http://purl.uniprot.org/uniprot/Q7TNF9 ^@ Similarity ^@ Belongs to the FAM117 family. http://togogenome.org/gene/10090:Mrc1 ^@ http://purl.uniprot.org/uniprot/Q61830 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Detected in macrophages.|||Down-regulated by interferon gamma.|||Endosome membrane|||Mediates the endocytosis of glycoproteins by macrophages. Binds both sulfated and non-sulfated polysaccharide chains. Acts as phagocytic receptor for bacteria, fungi and other pathogens. http://togogenome.org/gene/10090:Tas2r118 ^@ http://purl.uniprot.org/uniprot/P59529 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor T2R family.|||Cell membrane|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5 (By similarity).|||Interacts with RTP3 and RTP4.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Ski ^@ http://purl.uniprot.org/uniprot/B1AUF1 ^@ Similarity ^@ Belongs to the SKI family. http://togogenome.org/gene/10090:Ccnb2 ^@ http://purl.uniprot.org/uniprot/P30276 ^@ Developmental Stage|||Function|||Similarity|||Subunit ^@ Accumulates steadily during G2 and is abruptly destroyed at mitosis.|||Belongs to the cyclin family. Cyclin AB subfamily.|||Essential for the control of the cell cycle at the G2/M (mitosis) transition.|||Interacts with the CDK1 protein kinase to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. http://togogenome.org/gene/10090:Plg ^@ http://purl.uniprot.org/uniprot/P20918|||http://purl.uniprot.org/uniprot/Q3V1T9 ^@ Activity Regulation|||Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.|||Belongs to the peptidase S1 family. Plasminogen subfamily.|||Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin.|||Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Cannot be activated with streptokinase.|||In the presence of the inhibitor, the activation involves only cleavage after Arg-581, resulting in 2 chains held together by 2 disulfide bonds. Without the inhibitor, the activation involves also removal of the activation peptide.|||In the presence of the inhibitor, the activation involves only cleavage after Arg-581, yielding two chains held together by two disulfide bonds. In the absence of the inhibitor, the activation involves additionally the removal of the activation peptide (By similarity).|||Interacts (both mature PLG and the angiostatin peptide) with AMOT and CSPG4. Interacts (via the Kringle domains) with HRG; the interaction tethers PLG to the cell surface and enhances its activation. Interacts (via Kringle 4 domain) with ADA; the interaction stimulates PLG activation when in complex with DPP4. Angiostatin: Interacts with ATP5F1A; the interaction inhibits most of the angiogenic effects of angiostatin.|||Kringle domains mediate interaction with CSPG4.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells (By similarity).|||Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.|||Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot.|||Secreted http://togogenome.org/gene/10090:Pop5 ^@ http://purl.uniprot.org/uniprot/Q9DB28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic/archaeal RNase P protein component 2 family.|||Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.|||Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.|||nucleolus http://togogenome.org/gene/10090:Svop ^@ http://purl.uniprot.org/uniprot/Q8BFT9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Trappc6b ^@ http://purl.uniprot.org/uniprot/A0A1W2P7S5|||http://purl.uniprot.org/uniprot/Q9D289 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAPP small subunits family. BET3 subfamily.|||Component of a transport protein particle (TRAPP) complex that may function in specific stages of inter-organelle traffic (By similarity). Specifically involved in the early development of neural circuitry, likely by controlling the frequency and amplitude of intracellular calcium transients implicated in the regulation of neuron differentiation and survival (By similarity).|||Endoplasmic reticulum|||Homodimer (By similarity). Part of a TRAPP complex. Heterodimer with TRAPPC3 (By similarity). The heterodimer TRAPPC6B-TRAPPC3 interacts with TRAPPC1 likely providing a core for TRAPP complex formation (By similarity).|||Widely expressed. Expressed in lung, heart, liver, spleen, brain and kidney.|||cis-Golgi network http://togogenome.org/gene/10090:Ugt1a10 ^@ http://purl.uniprot.org/uniprot/E9PXN7|||http://purl.uniprot.org/uniprot/Q5FW80|||http://purl.uniprot.org/uniprot/Q6XL43 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Ctf1 ^@ http://purl.uniprot.org/uniprot/A0A0U1RNJ2|||http://purl.uniprot.org/uniprot/Q541U3|||http://purl.uniprot.org/uniprot/Q60753 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the IL-6 superfamily.|||Highly expressed in heart, skeletal muscle, liver, lung and kidney. Lower levels in testis and brain. No expression in spleen.|||Induces cardiac myocyte hypertrophy in vitro. Binds to and activates the ILST/gp130 receptor.|||Secreted http://togogenome.org/gene/10090:Cd101 ^@ http://purl.uniprot.org/uniprot/A8E0Y8 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Membrane|||N-glycosylated.|||Plays a role as inhibitor of T-cells proliferation induced by CD3. Inhibits expression of IL2RA on activated T-cells and secretion of IL2. Inhibits tyrosine kinases that are required for IL2 production and cellular proliferation. Inhibits phospholipase C-gamma-1/PLCG1 phosphorylation and subsequent CD3-induced changes in intracellular free calcium. Prevents nuclear translocation of nuclear factor of activated T-cell to the nucleus. Plays a role in the inhibition of T-cell proliferation via IL10 secretion by cutaneous dendritic cells (By similarity). http://togogenome.org/gene/10090:Hsd3b9 ^@ http://purl.uniprot.org/uniprot/E9Q007 ^@ Similarity ^@ Belongs to the 3-beta-HSD family. http://togogenome.org/gene/10090:Slc39a12 ^@ http://purl.uniprot.org/uniprot/Q5FWH7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ZIP transporter (TC 2.A.5) family.|||Highly expressed in brain, namely in the hippocampus, frontal cortex, striatum, hypothalamus, and cerebellum (at protein level) (PubMed:23716681, PubMed:35065654). Also expressed in neurons in the Purkinje cell layer of the cerebellum, medulla oblongata, and the frontal cortex (PubMed:23716681). Abundantly expressed in the testis, namely in the spermatogonia and spermatids within the seminiferous tubules (PubMed:35065654).|||Membrane|||Uniporter that promotes Zn(2+) import from the extracellular space to the cytoplasm across the cell membrane (PubMed:23716681, PubMed:35065654). The transport activity is temperature dependent (PubMed:23716681). May play a role in neurulation and neurite extension (PubMed:23716681). May play a key role in maintaining intracellular zinc content at levels that reduce the inhibitory effects of rises in oxidative stress on spermatogonia and spermatozoa viability during spermatogenesis (PubMed:35065654). http://togogenome.org/gene/10090:Cyrib ^@ http://purl.uniprot.org/uniprot/Q921M7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CYRI family.|||Expressed in pancreatic ducts (at protein level).|||Interacts with RAC1 (GTP-bound form preferentially).|||Membrane|||Mitochondrion|||Myeloid-specific conditional knockout mice have a reduced survival following Salmonella systemic infection. Upon infection, they show increased levels of several serum pro-inflammatory cytokines and chemokines produced by activated neutrophils and monocytes.|||Negatively regulates RAC1 signaling and RAC1-driven cytoskeletal remodeling (PubMed:31285585). Regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions. Limits Rac1 mediated activation of the Scar/WAVE complex, focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization (By similarity). Protects against Salmonella bacterial infection. Attenuates processes such as macropinocytosis, phagocytosis and cell migration and restrict sopE-mediated bacterial entry (PubMed:31285585). Restricts also infection mediated by Mycobacterium tuberculosis and Listeria monocytogenes (PubMed:31285585). Involved in the regulation of mitochondrial dynamics and oxidative stress (PubMed:29059164).|||Ubiquitinated at Lys-74 upon Salmonella bacterial infection. http://togogenome.org/gene/10090:Stk36 ^@ http://purl.uniprot.org/uniprot/Q69ZM6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 13.5 dpc is widely distributed in the forebrain, midbrain, hindbrain, spinal cord, somites, developing limb buds and skin.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Contaminating sequence. Sequence of unknown origin in the C-terminal part.|||Cytoplasm|||Interacts with SPAG16 and KIF27.|||Mice display profound growth retardation with a communicating form of hydrocephalus, nasal inflammation and early mortality.|||Nucleus|||Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors. Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization. GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur. Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia.|||Weakly expressed in the heart and thymus, present at moderate to high levels in the lungs, pancreas, and kidneys and at higher levels in the brain and cerebellum. Very highly expressed in the testis.|||cilium axoneme http://togogenome.org/gene/10090:Otoa ^@ http://purl.uniprot.org/uniprot/Q8K561 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the stereocilin family.|||Expressed in cochlea on the upper surface of the spiral limbus at 16.5 dpc onwards.|||Expressed in the inner ear and vestibule.|||May act as an adhesion molecule.|||extracellular matrix http://togogenome.org/gene/10090:Snx24 ^@ http://purl.uniprot.org/uniprot/Q9CRB0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||Cytoplasmic vesicle membrane|||May be involved in several stages of intracellular trafficking.|||The PX domain mediates specific binding to membranes enriched in phosphatidylinositol 3-phosphate (PtdIns(P3)). http://togogenome.org/gene/10090:Trat1 ^@ http://purl.uniprot.org/uniprot/Q3UU67 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Homodimer; disulfide-linked. Interacts with CD3Z. When phosphorylated, interacts with PIK3R1 (By similarity).|||Phosphorylated on tyrosines upon TCR activation.|||Present in T-cells (at protein level).|||Present in thymocytes from 16.5 dpc (at protein level).|||Stabilizes the TCR (T-cell antigen receptor)/CD3 complex at the surface of T-cells.|||Strongly expressed at 13.5 dpc, then down-regulated. Marginal in adult. Protein may be unstable. http://togogenome.org/gene/10090:Dip2c ^@ http://purl.uniprot.org/uniprot/B2RQ71 ^@ Similarity ^@ Belongs to the DIP2 family. http://togogenome.org/gene/10090:Slc7a6 ^@ http://purl.uniprot.org/uniprot/Q8BGK6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.|||Cell membrane|||Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.|||Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids such as L-arginine from inside the cells in exchange with neutral amino acids like L-leucine, L-glutamine and isoleucine, plus sodium ions and may participate in nitric oxide synthesis (By similarity). Also exchanges L-arginine with L-lysine in a sodium-independent manner (By similarity). The transport mechanism is electroneutral and operates with a stoichiometry of 1:1 (By similarity). Contributes to ammonia-induced increase of L-arginine uptake in cerebral cortical astrocytes leading to ammonia-dependent increase of nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) induction, and protein nitration (By similarity). May mediate transport of ornithine in retinal pigment epithelial (RPE) cells (By similarity). May also transport glycine betaine in a sodium dependent manner from the cumulus granulosa into the enclosed oocyte (PubMed:24599290).|||Strongest expression in brain but also detected in testis, parotis, small intestine, heart and kidney. Weakly expressed in spleen, lung and liver. http://togogenome.org/gene/10090:Bscl2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J225|||http://purl.uniprot.org/uniprot/Q9Z2E9 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the seipin family.|||Endoplasmic reticulum membrane|||Expressed in the paraventricular nucleus of the hypothalamus (PVN) and brainstem dorsal vagal complex (DVC) in oxytocin and catecholaminergic neurons (at protein level). Highest expression detected in subcutaneous and epididymal white adipose tissue, brown adipose tissue and testis. Also expressed in brain, skeletal muscle and adrenal gland, with lower levels detected in liver, heart, kidney, spleen, lung and small intestine. In brain, detected in piriform cortex, olfactory tubercle, islands of Calleja, lateral septal nucleus, medial septal nucleus, nucleus of the vertical limb of the diagonal band, nucleus of the horizontal limb of the diagonal band, preoptic area, paraventricular thalamic nucleus, lateral globus pallidus, supraoptic nucleus, suprachiasmatic nucleus, subfornical organ, paraventricular nucleus of the hypothalamus, zona incerta, dorsomedial nucleus of the hypothalamus, ventromedial nucleus of the hypothalamus, arcuate nucleus of the hypothalamus, basomedial amygdaloid nucleus, medial amygdaloid nucleus, medial habenular, pyramidal cell layer of the hippocampus, granular layer of the dentate gyrus, posterior hypothalamus, supramammilliary nucleus, premammillary nucleus, nucleus of Darkschewitsch, Edinger-Westphal nucleus, ventral tegmental area, dorsal raphe nucleus, periaqueductal gray, median raphe nucleus, lateral parabrachial nucleus, dorsal tegmental nucleus, laterodorsal tegmental nucleus, locus coeruleus, Barrington's nucleus, medial vestibular nucleus, ambiguous nucleus, dorsal vagal complex and hypoglossal nucleus.|||Lipid droplet|||Membrane|||Mutant mice display increased early postnatal mortality rate, reduction of total body fat mass, nearly total absence of gonadal fat and great reduction in subcutaneous fat. Mice have enlarged visceral organs, markedly steatotic liver, decreased adipocyte size and number, and display decreased levels of plasma adiponectin and leptin, glucose intolerance and insulin resistance but not hypertriglyceridemia.|||Plays a crucial role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis (By similarity).In association with LDAF1, defines the sites of LD formation in the ER (By similarity). Also required for growth and maturation of small nascent LDs into larger mature LDs (By similarity). Mediates the formation and/or stabilization of endoplasmic reticulum-lipid droplets (ER-LD) contacts, facilitating protein and lipid delivery from the ER into growing LDs (By similarity). Regulates the maturation of ZFYVE1-positive nascent LDs and the function of the RAB18-ZFYVE1 complex in mediating the formation of ER-LD contacts (By similarity). Binds anionic phospholipids including phosphatidic acid (By similarity). Plays an important role in the differentiation and development of adipocytes (PubMed:18458148, PubMed:19574402, PubMed:21551454, PubMed:22269949).|||Undecamer (an oligomer having eleven subunits) (By similarity). Oligomerization is important for its function in lipid droplet formation (By similarity). Interacts with LDAF1 to form an oligomeric complex (By similarity). Interacts with RAB18 (By similarity). Interacts with ZFYVE1 in a RAB18-dependent manner (By similarity).|||Up-regulated during in vitro adipocyte differentiation. http://togogenome.org/gene/10090:Rsbn1l ^@ http://purl.uniprot.org/uniprot/D3Z0K6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the round spermatid basic protein 1 family.|||Nucleus http://togogenome.org/gene/10090:Or12e13 ^@ http://purl.uniprot.org/uniprot/Q7TR35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Siglec1 ^@ http://purl.uniprot.org/uniprot/Q62230 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||By interferon-alpha (PubMed:26370074).|||Cell membrane|||Detected in lymph node in the subcapsular sinus, interfollicular regions, and T and B-cell boundary (at protein level). Expressed by macrophages in various tissues (PubMed:26370074). Highest expression in spleen and lymph node with lower amounts in lung, liver, bone marrow, heart and skin. No expression in thymus, kidney, brain or small intestine.|||Interacts with CLEC10A.|||Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells. Plays a crucial role in limiting bacterial dissemination by engaging sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response (PubMed:24788876). Mediates the uptake of various enveloped viruses via sialic acid recognition and subsequently induces the formation of intracellular compartments filled with virions (VCCs)(PubMed:26370074). In turn, enhances macrophage-to-T-cell transmission of several viruses including murine leukemia virus (PubMed:26370074). Acts as an endocytic receptor mediating clathrin dependent endocytosis. Preferentially binds to alpha-2,3-linked sialic acid (By similarity). Binds to SPN/CD43 on T-cells (By similarity). May play a role in hemopoiesis. Plays a role in the inhibition of antiviral innate immune by promoting TBK1 degradation via TYROBP and TRIM27-mediated ubiquitination (By similarity).|||SIGLEC1-deficient mice are viable, display no gross developmental abnormalities, and exhibit only subtle changes in B- and T-cell populations (PubMed:16449664). However, they are significantly more susceptible to bacterial infection than WT (PubMed:24788876). In addition, serum IgM and IgG amounts are greatly reduced in mutant mice (PubMed:16449664, PubMed:24788876).|||Secreted http://togogenome.org/gene/10090:Mmut ^@ http://purl.uniprot.org/uniprot/P16332 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methylmalonyl-CoA mutase family.|||Catalyzes the reversible isomerization of methylmalonyl-CoA (MMCoA) (generated from branched-chain amino acid metabolism and degradation of dietary odd chain fatty acids and cholesterol) to succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the tricarboxylic acid cycle.|||Cytoplasm|||Homodimer. Interacts (the apoenzyme form) with MMAA; the interaction is GTP dependent.|||Inhibited by itaconyl-CoA, a metabolite that inactivates the coenzyme B12 cofactor.|||Mitochondrion|||Mitochondrion matrix http://togogenome.org/gene/10090:Crb3 ^@ http://purl.uniprot.org/uniprot/Q8QZT4 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via C-terminus) with PALS1 (via PDZ domain) (PubMed:12527193). Interacts with PARD6A (By similarity). Interacts (via intracellular domain) with EPB41L5 (By similarity).|||Expressed in the apical renal tubules (at protein level) (PubMed:17920587). Expressed in the retinal pigment epithelium (PubMed:26404741).|||Expressed in the branchial arches, optic vesicle and mesonephric tubules of the kidney at 10.5 dpc (PubMed:17920587). Expressed in the internal endodermal layer and in the nascent bronchial tips of the lung at 11.5 dpc (PubMed:17920587).|||Involved in the establishment of cell polarity in mammalian epithelial cells (By similarity). Regulates the morphogenesis of tight junctions (PubMed:21145499). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (PubMed:21145499).|||The PDZ-binding motif is involved in the interactions with PARD6A and PALS1.|||tight junction http://togogenome.org/gene/10090:Tchhl1 ^@ http://purl.uniprot.org/uniprot/Q9D3P1 ^@ Similarity ^@ Belongs to the S-100 family. http://togogenome.org/gene/10090:Gnat2 ^@ http://purl.uniprot.org/uniprot/A2AE33|||http://purl.uniprot.org/uniprot/P50149 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.|||In the retina, expressed in the rod photoreceptors.|||Photoreceptor inner segment|||photoreceptor outer segment http://togogenome.org/gene/10090:Cd37 ^@ http://purl.uniprot.org/uniprot/Q3U429|||http://purl.uniprot.org/uniprot/Q4FK35|||http://purl.uniprot.org/uniprot/Q61470 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Interacts with SCIMP.|||Membrane http://togogenome.org/gene/10090:Zscan21 ^@ http://purl.uniprot.org/uniprot/Q07231 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed predominantly in the spermatocytes and spermatids of adult testes. It is also present at lower levels in the ovary, brain, spleen, embryo and fetus.|||First detected between 2 and 3 weeks after birth, in parallel with the onset and progression of meiosis. It is expressed during oogenesis from the pachytene stage of meiotic prophase through to postmeiotic cells. Expression in testis starts from postnatal day 7 (PND7) and expression remains constant until PND28 (PubMed:27492080).|||Male germ-cell-specific conditional knockout results in complete male infertility and meiotic arrest in spermatocytes (PubMed:27492080). Spermatocytes show impaired chromosomal synapsis and DNA double-strand breaks (DSB) repair and a significantly reduced expression of DSB repair-associated genes (PubMed:27492080).|||Nucleus|||Strong transcriptional activator (PubMed:1284028). Plays an important role in spermatogenesis; essential for the progression of meiotic prophase I in spermatocytes (PubMed:27492080). http://togogenome.org/gene/10090:Nos1ap ^@ http://purl.uniprot.org/uniprot/Q9D3A8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1. The complex formed with NOS1 and synapsins is necessary for specific NO and synapsin functions at a presynaptic level. Mediates an indirect interaction between NOS1 and RASD1 leading to enhance the ability of NOS1 to activate RASD1. Competes with DLG4 for interaction with NOS1, possibly affecting NOS1 activity by regulating the interaction between NOS1 and DLG4 (By similarity). In kidney podocytes, plays a role in podosomes and filopodia formation through CDC42 activation (PubMed:33523862).|||Interacts with the PDZ domain of NOS1 or the second PDZ domain of DLG4 through its C-terminus. Interacts with RASD1 and SYN1, SYN2 and SYN3 via its PID domain. Forms a ternary complex with NOS1 and SYN1 (By similarity). Forms a ternary complex with NOS1 and RASD1.|||filopodium|||podosome http://togogenome.org/gene/10090:Cd207 ^@ http://purl.uniprot.org/uniprot/Q8VBX4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells.|||Expressed by Langerhans cells. Expressed in dendritic cells and by scattered cells in lymph nodes and spleen. Also detected in some non-lymphoid tissues such as lung, liver and heart.|||Homotrimer.|||Membrane|||The C-type lectin domain mediates dual recognition of both sulfated and mannosylated glycans. http://togogenome.org/gene/10090:Whamm ^@ http://purl.uniprot.org/uniprot/Q571B6 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Aberrant splicing.|||Acts as a nucleation-promoting factor (NPF) that stimulates Arp2/3-mediated actin polymerization both at the Golgi apparatus and along tubular membranes. Involved as a regulator of Golgi positioning and morphology. Its activity in membrane tubulation requires F-actin and interaction with microtubules. Proposed to use coordinated actin-nucleating and microtubule-binding activities of distinct WHAMM molecules to drive membrane tubule elongation; when MT-bound can recruit and remodel membrane vesicles but is prevented to activate the Arp2/3 complex. Required for RhoD-dependent actin reorganization such as in cell adhesion and cell migration (By similarity). Participates in vesicle transport between the reticulum endoplasmic and the Golgi complex.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum-Golgi intermediate compartment|||Interacts with ACTR3; indicative for an association with the ARP2/3 complex. Associates with microtubules; in vitro binds to tubulin heterodimer in a 1:1 stoichiometry; decorates microtubules with a repeat of 80 A along protofilaments. Interacts with RHOD (in GTP-bound form).|||The N-terminal region associates with membranes, the coiled-coil region binds to microtubules and the WH2 domains promotes actin nucleation.|||cis-Golgi network http://togogenome.org/gene/10090:Mrps18a ^@ http://purl.uniprot.org/uniprot/Q5U5I3|||http://purl.uniprot.org/uniprot/Q99N85 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS18 family. Mitochondrion-specific ribosomal protein mL66 subfamily.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Hsp90b1 ^@ http://purl.uniprot.org/uniprot/P08113|||http://purl.uniprot.org/uniprot/Q3UAD6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 90 family.|||Endoplasmic reticulum lumen|||Homodimer; disulfide-linked. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with OS9 (By similarity). Interacts with AIMP1; regulates its retention in the endoplasmic reticulum. Interacts with CNPY3; this interaction is disrupted in the presence of ATP. Interacts with TLR4, TLR9 and TLR11, but not with TLR3. Interacts with MZB1 in a calcium-dependent manner. Interacts with METTL23 (By similarity). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (By similarity).|||Melanosome|||Molecular chaperone that functions in the processing and transport of secreted proteins (PubMed:20865800). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:20865800). Functions in endoplasmic reticulum associated degradation (ERAD) (By similarity). Has ATPase activity (PubMed:20865800). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (By similarity).|||N-glycosylated.|||Sarcoplasmic reticulum lumen http://togogenome.org/gene/10090:Vmn1r248 ^@ http://purl.uniprot.org/uniprot/D3YTX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Timm22 ^@ http://purl.uniprot.org/uniprot/B0QZS8|||http://purl.uniprot.org/uniprot/Q9CQ85 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tim17/Tim22/Tim23 family.|||Component of the TIM22 complex, whose core is composed of TIMM22, associated with peripheral protein FXC1/TIMM10B and the 70 kDa heterohexamer. In most cases, the 70 kDa complex is composed of TIMM9 and TIMM10 (TIMM10A or TIMM10B). A small fraction of the 70 kDa complex is composed of TIMM8 (TIMM8A/DDP1 or TIMM8B/DDP2) and TIMM13. The TIM22 complex also contains AGK and TIMM29. Interacts directly with TIMM9, TIMM10A and FXC1/TIMM10B. Interacts (when oxidized) with TIMM29; interaction is direct.|||Component of the TIM22 complex.|||Disulfide bonds promote efficient assembly of the TIM22 complex.|||Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps (By similarity).|||Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Serpinb6b ^@ http://purl.uniprot.org/uniprot/O08804 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Swsap1 ^@ http://purl.uniprot.org/uniprot/Q8VCI7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ ATPase which is preferentially stimulated by single-stranded DNA and is involved in homologous recombination repair (HRR). Has a DNA-binding activity which is independent of its ATPase activity (By similarity).|||Interacts with ZSWIM7; they form a functional complex involved in homologous recombination repair and stabilize each other. Interacts with RAD51, RAD51B, RAD51C, RAD51D and XRCC3; involved in homologous recombination repair (By similarity).|||Nucleus http://togogenome.org/gene/10090:Usp10 ^@ http://purl.uniprot.org/uniprot/P52479 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. USP10 subfamily.|||Cytoplasm|||Early endosome|||Found in a deubiquitination complex with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta (IL1B)-mediated NF-kappa-B activation by promoting IKBKG or TRAF6 deubiquitination. Interacts with IKBKG; this interaction increases in response to DNA damage. Interacts with TANK; this interaction increases in response to DNA damage. Interacts with TRAF6; this interaction increases in response to DNA damage. Interacts with ZC3H12A; this interaction increases in response to DNA damage. Interacts with G3BP1 (via NTF2 domain) and G3BP2 (via NTF2 domain); inhibiting stress granule formation.|||Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits. Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules. Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome. Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage. Deubiquitinates TBX21 leading to its stabilization.|||Nucleus|||Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus.|||Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes (By similarity).|||Ubiquitinated. Deubiquitinated by USP13 (By similarity). http://togogenome.org/gene/10090:Cryga ^@ http://purl.uniprot.org/uniprot/P04345 ^@ Domain|||Function|||Miscellaneous|||Similarity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||There are six different gamma crystallins identified in mouse lens. http://togogenome.org/gene/10090:Trpv6 ^@ http://purl.uniprot.org/uniprot/Q91WD2 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily.|||Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:12765696, PubMed:12601087, PubMed:12574114, PubMed:14736889, PubMed:15123711, PubMed:17129178). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (PubMed:17129178, PubMed:22878123). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation (PubMed:15123711). In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner (PubMed:12601087). Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (PubMed:12574114).|||Cell membrane|||Detected in intestine (at protein level) (PubMed:17129178). Abundantly expressed in pancreas and placenta, and to a much lesser extent in stomach and kidney (PubMed:12765696). Detected in kidney and duodenum (PubMed:17129178, PubMed:20399919).|||Glycosylated.|||Interacts with TCAF1 and TCAF2 (By similarity). Homotetramer and probably heterotetramer with TRPV5 (PubMed:12574114). Interacts with TRPV5 (PubMed:12574114). Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane (PubMed:12660155). Interacts with calmodulin (PubMed:12765696, PubMed:15123711). Interacts with BSPRY (PubMed:16380433).|||Mutant mice have lower body weight than their littermates throughout their lifespan and low fertility, due to impaired calcium homeostasis. Mutant mice display strongly impaired intestinal Ca(2+) uptake and increased urinary Ca(2+) levels (PubMed:17129178). Still, their serum Ca(2+) levels are normal, probably due to compensation by another calcium channel (PubMed:17129178, PubMed:20399919). In spite of this, mutant mice display decreased femoral mineral density; also when they are fed a high-calcium diet (PubMed:17129178). In contrast, no difference in bone density was observed in another study; mutant and wild-type mice displayed similar values when fed a normal diet, and a similar reduction in bone mass when fed a low-calcium diet (PubMed:20399919). Besides, the majority of mutant mice display alopecia and develop dermatitis (PubMed:17129178).|||Phosphorylation at Tyr-201 and Tyr-202 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at these sites by PTPN1 (By similarity).|||Unusual initiator. The initiator methionine is coded by a non-canonical ACG threonine codon.|||Up-regulated in intestine by exposure to a low-calcium diet (PubMed:17129178, PubMed:22878123). Down-regulated in intestine in response to a high-calcium diet (PubMed:17129178). http://togogenome.org/gene/10090:Fam3c ^@ http://purl.uniprot.org/uniprot/Q91VU0 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAM3 family.|||By TGF-beta in epithelial cells.|||Cytoplasmic vesicle|||Expressed at 15.5 dpc in the nonsensory epithelium of the inner ear and at lower levels in the vestibule of the inner ear, the brain and hair follicles. Expressed in the ganglion cell layer of the retina and in the ciliary body at 15.5 dpc. At later stages, retinal expression becomes restricted to the ganglion cell layer.|||May be involved in retinal laminar formation. Promotes epithelial to mesenchymal transition.|||Secreted|||Ubiquitously expressed, with highest levels in the retina. Up-regulated in mammary epithelial cells and hepatocytes undergoing epithelial to mesenchymal transition (at protein level). http://togogenome.org/gene/10090:Prl8a8 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0I6|||http://purl.uniprot.org/uniprot/Q9DAS4 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed specifically in the placenta. Predominantly expressed in spongiotrophoblast cells.|||Increases in abundance as gestation advanced. Predominandtly expressed in the junctional zone during the latter third of gestation.|||Secreted http://togogenome.org/gene/10090:Pogk ^@ http://purl.uniprot.org/uniprot/Q80TC5 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Lce1j ^@ http://purl.uniprot.org/uniprot/D3YUU5 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Nsmce3 ^@ http://purl.uniprot.org/uniprot/Q9CPR8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. NSMCE1, NSMCE4A or EID3 and NSMCE3 probably form a subcomplex that bridges the head domains of the SMC5:SMC6 heterodimer. Interacts with PJA1 (By similarity). Interacts with E2F1 (via C-terminus) (PubMed:14593116). Interacts with NGFR (via C-terminus) (PubMed:14593116). Interacts with NSMCE1. Interacts with NSMCE4. Interacts with SMC6. Interacts with EID3 (By similarity).|||Component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines and mediates sumoylation of shelterin complex (telosome) components which is proposed to lead to shelterin complex disassembly in ALT-associated PML bodies (APBs). In vitro enhances ubiquitin ligase activity of NSMCE1. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex (By similarity). May be a growth suppressor that facilitates the entry of the cell into cell cycle arrest (PubMed:14593116).|||Cytoplasm|||Nucleus|||Ubiquitous.|||telomere http://togogenome.org/gene/10090:Gjb5 ^@ http://purl.uniprot.org/uniprot/Q02739|||http://purl.uniprot.org/uniprot/Q542M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family.|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Expressed in skin, much lower in testis.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Bmal1 ^@ http://purl.uniprot.org/uniprot/Q9WTL8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated on Lys-544 by CLOCK during the repression phase of the circadian cycle (PubMed:18075593, PubMed:31294688). Acetylation facilitates recruitment of CRY1 protein and initiates the repression phase of the circadian cycle (PubMed:18075593). Acetylated at Lys-544 by KAT5 during the activation phase of the cycle, leading to recruitment of the positive transcription elongation factor b (P-TEFb) and BRD4, followed by productive elongation of circadian transcripts (PubMed:31294688). Deacetylated by SIRT1, which may result in decreased protein stability (PubMed:18662547).|||Component of the circadian clock oscillator which includes the CRY1/2 proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER1/2/3 proteins (PubMed:11779462). Forms a heterodimer with CLOCK (PubMed:9616112, PubMed:16717091, PubMed:16980631, PubMed:18662546, PubMed:19946213, PubMed:19330005, PubMed:21613214, PubMed:23970558, PubMed:22653727). The CLOCK-BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and BMAL1 (PubMed:11779462). Part of a nuclear complex which also includes RACK1 and PRKCA; RACK1 and PRKCA are recruited to the complex in a circadian manner (PubMed:20093473). Interacts with NPAS2 (PubMed:16628007). Interacts with EZH2 (PubMed:16717091, PubMed:23970558). Interacts with SUMO3 (PubMed:18644859). Interacts with SIRT1 (PubMed:18662546, PubMed:18662547, PubMed:19299583). Interacts with AHR (PubMed:20106950). Interacts with ID1, ID2 and ID3 (PubMed:20861012). Interacts with DDX4 (PubMed:22900038). Interacts with OGT (PubMed:23337503). Interacts with EED and SUZ12 (PubMed:23970558). Interacts with MTA1 (PubMed:24089055). Interacts with CIART (PubMed:24385426, PubMed:24736997). Interacts with HSP90 (By similarity). Interacts with KAT2B and EP300 (By similarity). Interacts with BHLHE40/DEC1 and BHLHE41/DEC2 (PubMed:12397359). Interacts with RELB and the interaction is enhanced in the presence of CLOCK (PubMed:22894897). Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a translocation to the nucleus (PubMed:18430226, PubMed:19605937, PubMed:20840750, PubMed:21613214, PubMed:24154698). Interaction of the CLOCK-BMAL1 heterodimer with PER or CRY inhibits transcription activation (PubMed:21613214). Interaction of the CLOCK-BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (PubMed:21613214). The CLOCK-BMAL1 heterodimer interacts with GSK3B (PubMed:19946213, PubMed:20049328). Interacts with KDM5A (PubMed:21960634). Interacts with KMT2A; in a circadian manner (PubMed:21113167). Interacts with UBE3A (By similarity). Interacts with PRKCG (PubMed:23185022). Interacts with MAGEL2 (PubMed:22208286). Interacts with NCOA2 (PubMed:24529706). Interacts with THRAP3 (PubMed:24043798). The CLOCK-BMAL1 heterodimer interacts with PASD1 (By similarity). Interacts with PASD1 (By similarity). Interacts with USP9X (PubMed:29626158). Interacts with PIWIL2 (via PIWI domain) (PubMed:28903391). Interacts with HDAC3 (PubMed:26776516). Interacts with HNF4A (By similarity).|||Cytoplasm|||Expressed in a circadian manner in the liver.|||Expressed in liver and testis (at protein level). Expressed in the suprachiasmatic nucleus (SCN) in a circadian manner (PubMed:29138967).|||Mice are characterized by reduced lifespan, and the presence of a number of pathologies characteristic of pre-mature aging and increased oxidative stress. They show impaired functional connectivity, increased oxidative damage and severe astrogliosis in the brain. They also exhibit accelerated thrombosis with elevated levels of thrombogenic factors, including VWF, SERPINE1/PAI1, and fibrinogen. Both male and female mice are infertile and male mice have low testosterone and high luteinizing hormone serum levels and a significant decrease in sperm count (PubMed:18258755, PubMed:22101268, PubMed:24270424, PubMed:24481314). Conditional knockout in myeloid cells increases the risk of sepsis lethality which is associated with elevated lactate production and CD274 expression in macrophages (PubMed:29996098). Myeloid-cell-specific BMAL1 and PKM2 double knockout reduces the risk of sepsis lethality which is associated with reduced serum lactate levels and reduced CD274 expression in macrophages (PubMed:29996098). Conditional knockout in skeletal muscle leads to impaired skeletal muscle triglyceride biosynthesis, accumulation of bioactive lipids and amino acids and reduced mitochondrial efficiency (PubMed:30096135).|||Nucleus|||O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-BMAL1 heterodimer thereby increasing CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2.|||PML body|||Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-97 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry. Dephosphorylation at Ser-85 is important for dimerization with CLOCK and transcriptional activity (By similarity).|||Sumoylated on Lys-266 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-BMAL1 heterodimer.|||The redox state of the cell can modulate the transcriptional activity of the CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers; NADH and NADPH enhance the DNA-binding activity of the heterodimers.|||Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. May play a role in spermatogenesis; contributes to the chromatoid body assembly and physiology. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (By similarity). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (By similarity). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (By similarity). Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504). Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (PubMed:29996098). Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B) (PubMed:30096135).|||Ubiquitinated, leading to its proteasomal degradation (PubMed:16980631, PubMed:18644859, PubMed:23185022, PubMed:26776516). Deubiquitinated by USP9X (PubMed:29626158).|||Undergoes lysosome-mediated degradation in a time-dependent manner in the liver. http://togogenome.org/gene/10090:Brdt ^@ http://purl.uniprot.org/uniprot/Q91Y44 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brdt is a promising target for male contraception. Inhibition by thienodiazepine inhibitor (+)-JQ1 that binds Asn-108, prevents recognition of acetylated histone H4. Treatment of mice with JQ1 reduces seminiferous tubule area, testis size and spermatozoa number and motility without affecting hormone levels. JQ1 causes a complete and reversible contraceptive effect in male mice (PubMed:22901802).|||Bromo domains mediate interaction with histones that have acetylated lysine residues at specific positions. Bromo domain 1 mediates binding with histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) (PubMed:19794495). The bromo domains also recognize and bind a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (PubMed:27105113).|||First detected when type B spermatogonia give rise to early meiotic cells (preleptotene, leptotene and zygotene) at 10-12 days post partum (dpp), producing a clearly detectable protein at 12 dpp (at protein level).|||Interacts with SMARCE1 (By similarity). Interacts with mRNA splicing machinery proteins SRSF2, DDX5, HNRNPK and TARDBP. Interacts with the acetylated N-terminus of histone H1, H2, H3 and H4. Interacts with P-TEFb components CDK9 and CCNT1/cyclin-T1.|||Mice are viable but males are sterile, producing fewer and morphologically abnormal sperm. Aberrant morphogenesis are first detected in step 9 elongating spermatids, and those elongated spermatids that are formed lack the distinctive foci of heterochromatin at the peri-nuclear envelope. Spermatid nuclei show a fragmented chromocenter.|||Nucleus|||Testis-specific chromatin protein that specifically binds histone H4 acetylated at 'Lys-5' and 'Lys-8' (H4K5ac and H4K8ac, respectively) and plays a key role in spermatogenesis (PubMed:12861021, PubMed:19794495, PubMed:22901802, PubMed:22922464). Required in late pachytene spermatocytes: plays a role in meiotic and post-meiotic cells by binding to acetylated histones at the promoter of specific meiotic and post-meiotic genes, facilitating their activation at the appropriate time. In the post-meiotic phase of spermatogenesis, binds to hyperacetylated histones and participates in their general removal from DNA (PubMed:22901802). Also recognizes and binds a subset of butyrylated histones: able to bind histone H4 butyrylated at 'Lys-8' (H4K8ac), while it is not able to bind H4 butyrylated at 'Lys-5' (H4K5ac) (PubMed:27105113). Also acts as a component of the splicing machinery in pachytene spermatocytes and round spermatids and participates in 3'-UTR truncation of specific mRNAs in post-meiotic spermatids (PubMed:22570411). Required for chromocenter organization, a structure comprised of peri-centromeric heterochromatin (PubMed:22020252).|||Testis-specific. Expressed in germinal cells from the early meiotic (pachytene) spermatocytes and during spermiogenesis in the round and elongating spermatids until the condensed late spermatids. No expression seen in spermatogonia. http://togogenome.org/gene/10090:Sez6l2 ^@ http://purl.uniprot.org/uniprot/Q4V9Z5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SEZ6 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed exclusively in the brain, predominantly in the neurons. Wide expression in the gray matter of the brain with high levels in the olfactory bulb, anterior olfactory nuclei, hippocampal formation and cerebellar cortex. Detected diffusely and weakly in the white matter, such as the corpus callosum and cerebellar medulla. In the cerebellar cortex, intensely expressed in Purkinje cells (PC) and granule cells. Detected also in interneurons in the molecular layer. Up-regulated at two weeks after birth.|||May contribute to specialized endoplasmic reticulum functions in neurons.|||Mice lacking Sez6, Sez6l1, Sez6l2 exhibit motor discordination, and PCs are ofen innervated by multiple climbing fibers with different neuronal origins in the cerebellum. http://togogenome.org/gene/10090:Krtap7-1 ^@ http://purl.uniprot.org/uniprot/Q9D3I6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 7 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Galnt14 ^@ http://purl.uniprot.org/uniprot/Q08EC9|||http://purl.uniprot.org/uniprot/Q8BVG5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Displays activity toward mucin-derived peptide substrates such as Muc2, Muc5AC, Muc7, and Muc13 (-58). May be involved in O-glycosylation in kidney (By similarity).|||Golgi apparatus membrane|||Membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Eef1akmt1 ^@ http://purl.uniprot.org/uniprot/A0A0D2X7Z2|||http://purl.uniprot.org/uniprot/Q9CY45 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM5 family.|||Cytoplasm|||Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-79'.|||Was originally thought to be an N(6)-adenine-specific DNA methyltransferase based on primary sequence and predicted secondary structure. http://togogenome.org/gene/10090:Ftdc2 ^@ http://purl.uniprot.org/uniprot/Q8BU47 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Tmem185b ^@ http://purl.uniprot.org/uniprot/Q8R3R5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM185 family.|||Membrane http://togogenome.org/gene/10090:Il17rb ^@ http://purl.uniprot.org/uniprot/Q543U7|||http://purl.uniprot.org/uniprot/Q9JIP3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Evi27 is a common site of retroviral integration in Bxh2 murine myeloid leukemias, localized near the Il17rb gene. Proviral integrations result in increased expression of Il17rb on the cell surface.|||Interacts with DAZAP2. Interacts with TRAF3IP2.|||Liver and testis. Expressed at lower level in kidney and lung. Expressed in selected T-cell, B-cell and myeloid cell lines.|||Membrane|||Receptor for the pro-inflammatory cytokines IL17B and IL17E. May play a role in controlling the growth and/or differentiation of hematopoietic cells.|||Secreted http://togogenome.org/gene/10090:Nppa ^@ http://purl.uniprot.org/uniprot/P05125 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the natriuretic peptide family.|||Cell projection|||Cleavage by MME initiates degradation of the factor and thereby regulates its activity. Degradation by IDE results in reduced activation of NPR1 (in vitro). During IDE degradation, the resulting products can temporarily stimulate NPR2 to produce cGMP, before the fragments are completely degraded and inactivated by IDE (in vitro).|||Degraded by IDE.|||Homodimer; disulfide-linked antiparallel dimer.|||Hormone produced in the kidneys that appears to be important for maintaining cardio-renal homeostasis. Mediates vasodilation, natriuresis and diuresis primarily in the renal system, in order to maintain the extracellular fluid volume and control the fluid-electrolyte balance. Specifically binds and stimulates cGMP production by renal transmembrane receptors, likely NPR1. Urodilatin not ANP, may be the natriuretic peptide responsible for the regulation of sodium and water homeostasis in the kidney.|||Hormone that plays a key role in mediating cardio-renal homeostasis, and is involved in vascular remodeling and regulating energy metabolism (PubMed:8760210, PubMed:22437503, PubMed:12890708). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins, such as PRKG1, that drive various biological responses (PubMed:12890708). Regulates vasodilation, natriuresis, diuresis and aldosterone synthesis and is therefore essential for regulating blood pressure, controlling the extracellular fluid volume and maintaining the fluid-electrolyte balance (PubMed:8760210, PubMed:22437503). Also involved in inhibiting cardiac remodeling and cardiac hypertrophy by inducing cardiomyocyte apoptosis and attenuating the growth of cardiomyocytes and fibroblasts (By similarity). Plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus, and thus prevents pregnancy-induced hypertension (PubMed:22437503). In adipose tissue, acts in various cGMP- and PKG-dependent pathways to regulate lipid metabolism and energy homeostasis (By similarity). This includes up-regulating lipid metabolism and mitochondrial oxygen utilization by activating the AMP-activated protein kinase (AMPK), and increasing energy expenditure by acting via MAPK11 to promote the UCP1-dependent thermogenesis of brown adipose tissue (By similarity). Binds the clearance receptor NPR3 which removes the hormone from circulation (By similarity).|||May have a role in cardio-renal homeostasis through regulation of diuresis and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. May have a role in potassium excretion but not sodium excretion (natriuresis). Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption.|||May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis and in vitro, vasodilates renal artery strips.|||May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal and vascular smooth muscle strips.|||May have a role in cardio-renal homeostasis through regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, selectively vasodilates intestinal smooth muscle but not vascular smooth muscle strips.|||May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, and vasodilation. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase. However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis. Appears to bind to specific receptors that are distinct from the receptors bound by the atrial natriuretic and long-acting natriuretic peptides. Possibly functions in protein excretion in urine by maintaining the integrity of the proximal tubules and enhancing protein excretion by decreasing proximal tubular protein reabsorption.|||May have a role in cardio-renal homeostasis through regulation of natriuresis, diuresis, vasodilation, and inhibiting aldosterone synthesis. In vitro, promotes the production of cGMP and induces vasodilation. May promote natriuresis, at least in part, by enhancing prostaglandin E2 synthesis resulting in the inhibition of renal Na+-K+-ATPase (By similarity). However reports on the involvement of this peptide in mammal blood volume and blood pressure homeostasis are conflicting; according to a report, in vivo it is not sufficient to activate cGMP and does not inhibit collecting duct transport nor effect diuresis and natriuresis (By similarity). Appears to bind to specific receptors that are distinct from the receptors bound by atrial natriuretic peptide and vessel dilator. Possibly enhances protein excretion in urine by decreasing proximal tubular protein reabsorption (By similarity).|||May have a role in cardio-renal homeostasis through regulation of regulation of natriuresis and vasodilation. In vivo promotes natriuresis. In vitro, vasodilates intestinal smooth muscle but not smooth muscle strips.|||Mice display increased arterial blood pressure which is dietary salt intake independent (PubMed:8760210). During pregnancy, increased blood pressure is observed, leading to late gestational proteinuria and smaller litters (PubMed:22437503). Impaired trophoblast invasion and smaller spiral arteries are also observed in 12.5 dpc embryos (PubMed:22437503). In 18.5 dpc embryos, mice display fewer trophoblasts and smaller arteries in the decidua and myometrium than those in wild-type mice (PubMed:22437503).|||Perikaryon|||Phosphorylation on Ser-128 decreases vasorelaxant activity.|||Results concerning the involvement of this peptide in blood volume and blood pressure homeostasis are conflicting. Several studies utilising in vitro and heterologous expression systems show that it is able to activate cGMP and promote vasodilation and natriuresis (By similarity). However, a heterologous and in vivo expression study in rat found that it is not sufficient to induce any diuretic, natriuretic, nor hypotensive responses, and is unable to bind NPR1 nor increase guanylyl cyclase activity (By similarity).|||Results concerning the involvement of this peptide in blood volume and blood pressure homeostasis are conflicting. Several studies utilising in vitro and heterologous expression systems show that it is able to activate cGMP and promote vasodilation and natriuresis (By similarity). However, an in vivo study in rat found that it is not sufficient to induce any diuretic, natriuretic, nor hypotensive responses, and is unable to bind NPR1 nor increase guanylyl cyclase activity (By similarity).|||Secreted|||The precursor molecule is proteolytically cleaved by CORIN at Arg-122 to produce atrial natriuretic peptide (PubMed:11884416, PubMed:15637153). Undergoes further proteolytic cleavage by unknown proteases to give rise to long-acting natriuretic peptide, vessel dilator and kaliuretic peptide (By similarity). Additional processing gives rise to the auriculin and atriopeptin peptides (By similarity). In the kidneys, alternative processing by an unknown protease results in the peptide urodilatin (By similarity). http://togogenome.org/gene/10090:Cox7a2l ^@ http://purl.uniprot.org/uniprot/E9PZS8|||http://purl.uniprot.org/uniprot/Q3UDK5|||http://purl.uniprot.org/uniprot/Q61387 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIIa family.|||By estrogen and silica.|||Interacts with the mitochondrial respiratory supercomplex.|||Involved in the regulation of oxidative phosphorylation and energy metabolism (PubMed:23857330, PubMed:23812712). Necessary for the assembly of mitochondrial respiratory supercomplex (PubMed:23857330, PubMed:23812712).|||Knockout homozygous mice manifest decreased mitochondrial respiratory activities and impaired formation of mitochondrial supercomplexes in muscles. KO animals have muscle weakness and exhibit heat production failure in the cold.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Usp32 ^@ http://purl.uniprot.org/uniprot/F8VPZ3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C19 family.|||Deubiquitinase that can remove conjugated ubiquitin from target proteins, such as RAB7A and LAMTOR1 (By similarity). Acts as a positive regulator of the mTORC1 signaling by mediating deubiquitination of LAMTOR1, thereby promoting the association between LAMTOR1 and the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (By similarity).|||Golgi apparatus membrane http://togogenome.org/gene/10090:Ins1 ^@ http://purl.uniprot.org/uniprot/P01325 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the insulin family.|||Heterodimer of a B chain and an A chain linked by two disulfide bonds.|||Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.|||Secreted http://togogenome.org/gene/10090:Gpr173 ^@ http://purl.uniprot.org/uniprot/Q6PI62 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level) (PubMed:30933929). Expressed in preadipocytes (PubMed:30251651).|||Is a receptor for the SMIM20 derived peptides Phoenixin-14 and Phoenixin-20 (PubMed:27268078). It mediates the Phoenixin-14 and Phoenixin-20 augmentation of gonadotropin-releasing hormone (GNRH) signaling in the hypothalamus and pituitary gland (PubMed:27268078). In the ovary, it mediates the effects of Phoenixin-14 and Phoenixin-20 induced granulosa cell proliferation during follicular growth (PubMed:30933929). http://togogenome.org/gene/10090:Dynlt3 ^@ http://purl.uniprot.org/uniprot/P56387|||http://purl.uniprot.org/uniprot/Q542J7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Probably binds BUB3 as part of transport cargo. Required for the efficient progression through mitosis.|||Belongs to the dynein light chain Tctex-type family.|||Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. DYNLT1 and DYNLT3 compete for association with dynein IC (DYNC1I1 or DYNC1I2). Self-associates. Interacts with DYNC1I1 and DYNC1I2. Interacts with BUB3. Interacts with SATB1 in nucleus to form complex with matrix attachment regions (MARs) of DNA (By similarity).|||Nucleus|||cytoskeleton|||kinetochore http://togogenome.org/gene/10090:Dok5 ^@ http://purl.uniprot.org/uniprot/Q91ZM9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the DOK family. Type B subfamily.|||DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK5 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway. Putative link with downstream effectors of RET in neuronal differentiation.|||In 12.5 dpc and 13 dpc embryos, it is expressed in the central nervous system, e.g. in the neural tube, the dorsal root and the cranial ganglion.|||Interacts with phosphorylated RET. In contrast to other DOK proteins, it does not interact with RASGAP.|||PTB domain mediates receptor interaction.|||Phosphorylated on tyrosine residues in response to insulin, IGF1 and GDNF.|||Specifically expressed in the brain, with a high specificity for neurons. http://togogenome.org/gene/10090:Or8b38 ^@ http://purl.uniprot.org/uniprot/Q7TRE0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or2y1c ^@ http://purl.uniprot.org/uniprot/Q7TQT0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or52ab4 ^@ http://purl.uniprot.org/uniprot/Q8VG01 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Etfbkmt ^@ http://purl.uniprot.org/uniprot/Q80ZM3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. ETFBKMT family.|||Cytoplasm|||Interacts with HSPD1; this protein may possibly be a methylation substrate.|||Mitochondrion matrix|||Protein-lysine methyltransferase that selectively trimethylates the flavoprotein ETFB in mitochondria. Thereby, may negatively regulate the function of ETFB in electron transfer from Acyl-CoA dehydrogenases. http://togogenome.org/gene/10090:Adcyap1r1 ^@ http://purl.uniprot.org/uniprot/E9Q3E8|||http://purl.uniprot.org/uniprot/E9Q968|||http://purl.uniprot.org/uniprot/P70205|||http://purl.uniprot.org/uniprot/Q6NXJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Interacts (via N-terminal extracellular domain) with ADCYAP1.|||Membrane|||This is a receptor for PACAP-27 and PACAP-38. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. May regulate the release of adrenocorticotropin, luteinizing hormone, growth hormone, prolactin, epinephrine, and catecholamine. May play a role in spermatogenesis and sperm motility. Causes smooth muscle relaxation and secretion in the gastrointestinal tract. http://togogenome.org/gene/10090:Ift88 ^@ http://purl.uniprot.org/uniprot/Q61371 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cilia absent or reduced, virtually no cilia of the normal 5 uM mean length (PubMed:21289087). Conditional knockdown in preadipocytes results in loss of cilia. Mutant mice show a significant reduction of gonadal white adipose tissue and total fat mass associated with reduced serum LEP levels (PubMed:31761534).|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:19253336, PubMed:23810713). Interacts with IFT20, IFT22, IFT25, IFT27, IFT52, TRAF3IP1, IFT74, IFT80 and IFT81 (PubMed:19253336). Interacts with IFT172 (PubMed:11062270). Interacts with IFT57 (PubMed:11062270, PubMed:19253336, PubMed:23810713). Interacts with IFT46 (PubMed:19253336, PubMed:17312020). Interacts with IFT70B (PubMed:23810713). Interacts with C2CD3 (PubMed:24469809). Interacts with ENTR1 (via N-terminus) (By similarity). Interacts with LRRC56 (By similarity). Interacts with DZIP1 (PubMed:23955340).|||Cytoplasm|||Defects in Ift88 are the cause of recessive bilateral polycystic kidney disease (PKD) with collecting duct and tubule ectasia, and a liver lesion involving biliary dysplasia and/or portal fibrosis.|||Positively regulates primary cilium biogenesis (PubMed:31761534, PubMed:11062270, PubMed:21289087). Also involved in autophagy since it is required for trafficking of ATG16L and the expansion of the autophagic compartment.|||Testis.|||centriole|||centrosome|||cilium|||cilium basal body|||flagellum http://togogenome.org/gene/10090:Catsper3 ^@ http://purl.uniprot.org/uniprot/Q80W99 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:17227845, PubMed:21224844, PubMed:34998468). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (PubMed:34998468).|||Contaminating sequence.|||Detected in hte testis during postnatal development at day 15. Restricted to the late-stage germline cells that line the seminiferous tubules.|||In contrast to the human ortholog, not activated by progesterone.|||Mice are normal but males are sterile. Male sterility is due to defects in sperm motility unability to fertilize intact eggs.|||Testis-specific.|||Voltage-gated calcium channel that plays a central role in sperm cell hyperactivation. Controls calcium entry to mediate the hyperactivated motility, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Activated by intracellular alkalinization.|||flagellum membrane http://togogenome.org/gene/10090:Oit3 ^@ http://purl.uniprot.org/uniprot/Q8R4V5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression begins as early as 6.5 dpc and very early in fetal liver (at least from 11.5 dpc). Expression level changes in different developmental stages. Levels decrease to a minimal level at 17.5 dpc and then increase gradually to the maximal level at about 7 days after birth.|||Liver-specific. Expressed only in the hepatocytes.|||May be involved in hepatocellular function and development.|||Nucleus envelope http://togogenome.org/gene/10090:Zdhhc24 ^@ http://purl.uniprot.org/uniprot/Q6IR37 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DHHC palmitoyltransferase family.|||Membrane|||Probable palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Aqp4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Z3|||http://purl.uniprot.org/uniprot/P55088|||http://purl.uniprot.org/uniprot/Q50H70|||http://purl.uniprot.org/uniprot/Q8BR89 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Basolateral cell membrane|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Cell projection|||Detected in brain cortex, especially around cortical blood vessels, and subjacent to pia, with lower levels in parenchymal membranes (PubMed:27751903). Detected in ependymal and astroglial cells in brain (PubMed:8660998, PubMed:9276712, PubMed:22896675, PubMed:27751903). Detected in supporting Hensen's cells, inner sulcus cells and Claudius cells in the inner ear (PubMed:11406631). Detected in skeletal muscle (PubMed:29055082). Detected in gastric parietal cells (PubMed:10915655). Detected in principal cells in collecting ducts in kidney medulla (at protein level) (PubMed:9276712, PubMed:16641094). Detected in brain, heart and skeletal muscle (PubMed:8660998).|||Endosome membrane|||Forms a water-specific channel (PubMed:8660998, PubMed:9276712, PubMed:18286643). Plays an important role in brain water homeostasis and in glymphatic solute transport (PubMed:22896675, PubMed:27751903, PubMed:30561329, PubMed:30557661). Required for a normal rate of water exchange across the blood brain interface (PubMed:30557661). Required for normal levels of cerebrospinal fluid influx into the brain cortex and parenchyma along paravascular spaces that surround penetrating arteries, and for normal drainage of interstitial fluid along paravenous drainage pathways. Thereby, it is required for normal clearance of solutes from the brain interstitial fluid, including soluble beta-amyloid peptides derived from APP (PubMed:22896675, PubMed:27751903, PubMed:30561329). Plays a redundant role in urinary water homeostasis and urinary concentrating ability (PubMed:9276712).|||Homotetramer. The tetramers can form oligomeric arrays in membranes. The size of the oligomers differs between tissues and is smaller in skeletal muscle than in brain. Interaction between AQP4 oligomeric arrays in close-by cells can contribute to cell-cell adhesion (By similarity). Part of a complex containing MLC1, TRPV4, HEPACAM and ATP1B1 (By similarity).|||Isoform 2: Palmitoylated on its N-terminal region. Isoform 1: Not palmitoylated.|||Membrane|||Mice are born at the expected Mendelian rate and display no obvious phenotype (PubMed:9276712, PubMed:10915655). They have normal urine osmolality under standard conditions, but display reduced urine osmolality after 36 hour water deprivation (PubMed:9276712). Adult mice display incereased brain water content (PubMed:27751903). Mutant mice display a reduced rate of water flux across the blood brain interface (PubMed:30557661). Fluid transport from the brain paravascular space into the surrounding interstitium is abolished. Besides, mice display strongly reduced solute clearance from the brain interstitium (PubMed:22896675). Mice display reduced cerebrospinal fluid influx into the brain, and reduced brain solute transport via the cerebrospinal fluid from the cisterna to the brain parenchyma (PubMed:22896675, PubMed:30561329). The organ of Corti in the inner ear appears morphologically normal, but mice have considerably impaired hearing at an age of 4 to 5 weeks (PubMed:11406631). Mice display unchanged gastric acid secretion (PubMed:10915655).|||Phosphorylation by PKC at Ser-180 reduces conductance by 50% (By similarity). Phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40%; this increase is not due to increased presence at the cell membrane (PubMed:18286643).|||sarcolemma http://togogenome.org/gene/10090:Tjp1 ^@ http://purl.uniprot.org/uniprot/B9EHJ3|||http://purl.uniprot.org/uniprot/P39447 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAGUK family.|||Cell membrane|||Homodimer (By similarity). Forms heterodimers TJP3 (By similarity). Forms a heterodimer (via PDZ2 domain) with TJP2/ZO2 (via PDZ2 domain) (PubMed:10026224). Interacts with OCLN, CALM, claudins, CGN/cingulin, CXADR, GJD3 and UBN1 (PubMed:10601346). Interacts (via ZU5 domain) with CDC42BPB (By similarity). Interacts (via PDZ domain) with GJA1 (By similarity). Interacts (via PDZ domains) with ANKRD2 (By similarity). Interacts with BVES (via the C-terminus cytoplasmic tail) (PubMed:16188940). Interacts with GJA12 and KIRREL1 (PubMed:12424224, PubMed:15183511). Interacts with HSPA4 (By similarity). Interacts (via ZU5 domain) with MYZAP (PubMed:20093627). Interacts with DLL1 (PubMed:24715457). Interacts with USP53 (via the C-terminal region) (PubMed:26609154). Interacts with DNMBP (via C-terminal domain); required for the apical cell-cell junction localization of DNMBP (By similarity). Interacts with SPEF1 (By similarity). Interacts (via N-terminus) with CTNNA1 (PubMed:10026224). Interacts with CLDN18 (PubMed:29400695).|||I band|||Membrane|||Phosphorylated at tyrosine redidues in response to epidermal growth factor (EGF) (By similarity). This response is dependent on an intact actin microfilament system (By similarity). Dephosphorylated by PTPRJ (By similarity).|||The 244-aa domain between residues 633 and 876 is the primary occludin (Ocln)-binding site and is required for stable association with the tight junction (By similarity).|||The C-terminal region (residues 1151-1372) is an actin-binding region (ABR) that interacts directly with F-actin and plays an important role in the localization of Tjp1 at junctions (By similarity). The ABR is also required for the localization to puncta at the free edge of cells before initiation of cell-cell contact (By similarity). The ABR is also necessary for Tjp1 recruitment to podosomes (By similarity).|||The second PDZ domain (PDZ2) mediates homodimerization and heterodimerization with Tjp2 and Tjp3 (By similarity). PDZ2 domain also mediates interaction with Gja12 (PubMed:15183511).|||Tjp1, TjpP2, and Tjp3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting Cdc42bpb to the leading edge of migrating cells (By similarity). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (By similarity). With Tjp2 and TJjp3, participates in the junctional retention and stability of the transcription factor Dbpa, but is not involved in its shuttling to the nucleus (By similarity).|||gap junction|||tight junction http://togogenome.org/gene/10090:Prkg2 ^@ http://purl.uniprot.org/uniprot/Q8C4R2|||http://purl.uniprot.org/uniprot/Q8CAH8 ^@ Similarity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily. http://togogenome.org/gene/10090:Khdc1b ^@ http://purl.uniprot.org/uniprot/P0C7A0 ^@ Similarity ^@ Belongs to the KHDC1 family. http://togogenome.org/gene/10090:Ovch2 ^@ http://purl.uniprot.org/uniprot/Q7M761 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Knockout male mice lacking OVCH2 are sterile.|||May be required for sperm ADAM3 processing and consequential sperm fertilizing ability (PubMed:32499443). In vitro, has an endopeptidase activity (By similarity).|||Only expressed in uterus tissue (PubMed:20810007). Expressed in the initial segment (IS) of the caput epididymis, the region most proximal to the testis (PubMed:32499443).|||Secreted http://togogenome.org/gene/10090:Setd1b ^@ http://purl.uniprot.org/uniprot/Q3URP1|||http://purl.uniprot.org/uniprot/Q8CFT2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Chromosome|||Component of the SET1B/COMPASS complex composed of the catalytic subunit SETD1A, WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1, DPY30 homotrimer and BOD1. Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity. Interacts with HCFC1 and ASH2L/ASH2. Interacts (via the RRM domain) with WDR82. Interacts (via the RRM domain) with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) only in the presence of WDR82. Binds specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each heptad. Interacts with RBM15. Interacts (via WIN motif) with WDR5.|||During preimplantation development expressed through all stages from oocyte to blastocyst. High expression is detected in oocyte that declines to a stable level from the 8-cell stage until 8.5 dpc. Expressed in the blastocyst in both the inner cell mass and the trophectoderm.|||Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place (By similarity). Plays an essential role in regulating the transcriptional programming of multipotent hematopoietic progenitor cells and lymphoid lineage specification during hematopoiesis (PubMed:29916805).|||Mutant embryos show growth retardation from 7.5 dpc and die before 11.5 dpc.|||Nucleus|||Nucleus speckle|||Widely expressed. http://togogenome.org/gene/10090:Tmem229a ^@ http://purl.uniprot.org/uniprot/B9EJI9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM229 family.|||Membrane http://togogenome.org/gene/10090:Ikbip ^@ http://purl.uniprot.org/uniprot/Q9DBZ1 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation ^@ Endoplasmic reticulum membrane|||N-glycosylated at Asn-151.|||Shares a common promoter with APAF1 from which the 2 genes are transcribed in opposite directions.|||Target of p53/TP53 with pro-apoptotic function. http://togogenome.org/gene/10090:Cryaa ^@ http://purl.uniprot.org/uniprot/A0A494B9Q6|||http://purl.uniprot.org/uniprot/P24622|||http://purl.uniprot.org/uniprot/Q546L9|||http://purl.uniprot.org/uniprot/Q569M7 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-93 may increase chaperone activity.|||Belongs to the small heat shock protein (HSP20) family.|||Constitutes approximately 10% of the total alpha-A-crystallin in the lens.|||Contributes to the transparency and refractive index of the lens. Acts as a chaperone, preventing aggregation of various proteins under a wide range of stress conditions. Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA.|||Cytoplasm|||Heteropolymer composed of three CRYAA and one CRYAB subunits. Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens. Can also form homodimers and homotetramers (dimers of dimers) which serve as the building blocks of homooligomers (By similarity). Within homooligomers, the zinc-binding motif is created from residues of 3 different molecules. His-123 and Glu-125 from one molecule are ligands of the zinc ion, and His-130 and His-177 residues from additional molecules complete the site with tetrahedral coordination geometry (By similarity). Part of a complex required for lens intermediate filament formation composed of BFSP1, BFSP2 and CRYAA (By similarity).|||May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions.|||Nucleus|||Undergoes age-dependent proteolytical cleavage at the C-terminus. http://togogenome.org/gene/10090:Or2m12 ^@ http://purl.uniprot.org/uniprot/Q8VF87 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhox2a ^@ http://purl.uniprot.org/uniprot/G3UYY0|||http://purl.uniprot.org/uniprot/Q9D4Y3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Cr1l ^@ http://purl.uniprot.org/uniprot/Q64735 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. Also acts as a decay-accelerating factor, preventing the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade. Plays a crucial role in early embryonic development by maintaining fetomaternal tolerance. Also acts as a costimulatory factor for T-cells which favors IL-4 secretion.|||Belongs to the receptors of complement activation (RCA) family.|||Death between 9.5 and 13.5 dpc from developmental arrest.|||Highly expressed in trophoblasts at 7.5 dpc, and in the maternally derived decidual tissues until 16 dpc. Expressed only at low levels in the embryo itself.|||Interacts with C3b.|||Membrane|||Ubiquitously expressed (at protein level). http://togogenome.org/gene/10090:Hnf1b ^@ http://purl.uniprot.org/uniprot/P27889 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HNF1 homeobox family.|||Binds DNA as a dimer. Can form homodimer or heterodimer with HNF1-alpha (By similarity). Interacts (via HNF-p1 domain) with PCBD1; the interaction increases its transactivation activity (By similarity).|||Nucleus|||Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (By similarity). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity). Transcriptional activity is increased by coactivator PCBD1 (By similarity). http://togogenome.org/gene/10090:Zfp110 ^@ http://purl.uniprot.org/uniprot/A0A0R4J249|||http://purl.uniprot.org/uniprot/Q923B3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Interacts with NGFR/p75(NTR). Interacts (via KRAB 1 domain) with TRAF6. Interacts (when ubiquitinated at Lys-15) with SQSTM1/p62.|||Lethal in a C57BL/6 background, while mice in a 129/Sv background are viable and healthy to adulthood. Mice in a C57BL/6 background do not survive beyond 12 dpc. Mice in a 129/Sv background may survive due to the presence of Nrif2/Zfp369, which is up-regulated in Nrif1 mutant mice in the 129/Sv background.|||Nucleus|||Transcription regulator involved in NGFR/p75(NTR)-mediated apoptosis. Essential component of the NGFR/p75(NTR) apoptotic pathway: upon ligand-binding and subsequent cleavage of NGFR/p75(NTR), binds to the intracellular domain (ICD) cleavage product of NGFR/p75(NTR), translocates to the nucleus and induces apoptosis, possibly by regulating expression of key regulators of apoptosis. Induces NGFR/p75(NTR)-mediated apoptosis in retina and sympathetic neurons. May also regulate expression of neuronal cholesterol biosynthesis genes. Probably acts as a transcription repressor: specifically binds to the 3'-end of zinc-finger coding genes and recruiting chromatin-modifying proteins such as SETDB1 and TRIM28/KAP1, leading to transcription repression.|||Ubiquitinated by TRAF6 at Lys-15 through 'Lys-63'-linked polyubiquitination. 'Lys-63'-linked polyubiquitination occurs in response to NGFR/p75(NTR) cleavage by gamma-secretase and promotes binding with the ICD cleavage product of NGFR/p75(NTR), followed by translocation into the nucleus and subsequent apoptosis.|||Ubiquitously expressed at low level. Expressed at higher level in testis. http://togogenome.org/gene/10090:Hycc2 ^@ http://purl.uniprot.org/uniprot/Q8C729 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Hyccin family.|||Cell membrane|||Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2).|||Expressed in the central nervous system. Expressed at much lower level in oligodendrocytes than in neurons.|||cytosol http://togogenome.org/gene/10090:Sdha ^@ http://purl.uniprot.org/uniprot/Q8K2B3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-498 and Lys-538 is observed in liver mitochondria from fasted mice but not from fed mice. Deacetylated by SIRT3.|||Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.|||Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD (By similarity). Interacts with SDHAF2/SDH5; interaction is required for FAD attachment (By similarity). Interacts with TRAP1 (By similarity). Interacts with LACC1 (By similarity).|||Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Can act as a tumor suppressor.|||Mitochondrion inner membrane|||Phosphorylation at Tyr-215 is important for efficient electron transfer in complex II and the prevention of ROS generation. http://togogenome.org/gene/10090:Pth2r ^@ http://purl.uniprot.org/uniprot/Q91V95 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 2 family.|||Binds to TIPF39/TIP39.|||Cell membrane|||This is a specific receptor for parathyroid hormone. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. PTH2R may be responsible for PTH effects in a number of physiological systems. It may play a significant role in pancreatic function. PTH2R presence in neurons indicates that it may function as a neurotransmitter receptor (By similarity). http://togogenome.org/gene/10090:Mug2 ^@ http://purl.uniprot.org/uniprot/P28666 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A proteinase activates the inhibitor by specific proteolysis in the bait region, which, by an unknown mechanism leads to reaction at the cysteinyl-glutamyl internal thiol ester site and to a conformational change, whereby the proteinase is trapped and/or covalently bound to the inhibitor. While in the tetrameric proteinase inhibitors steric inhibition is sufficiently strong, monomeric forms need a covalent linkage between the activated glutamyl residue of the original thiol ester and a terminal amino group of a lysine or another nucleophilic group on the proteinase, for inhibition to be effective.|||Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.|||Monomer.|||Plasma.|||Secreted http://togogenome.org/gene/10090:Zfyve19 ^@ http://purl.uniprot.org/uniprot/Q9DAZ9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cleavage furrow|||Interacts (via MIM1-B) with VPS4A; interaction takes place at the midbody ring following cytokinesis checkpoint activation.|||Key regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. Together with CHMP4C, required to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ZFYVE19/ANCHR and VPS4 and subsequent abscission (By similarity).|||Midbody ring|||The FYVE-type zinc finger mediates binding to phosphatidylinositol-3-phosphate (PtdIns(3)P).|||The MIM1-B motif mediates interaction with VPS4A.|||centrosome http://togogenome.org/gene/10090:Or7e169 ^@ http://purl.uniprot.org/uniprot/Q8VFF7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ggt5 ^@ http://purl.uniprot.org/uniprot/Q9Z2A9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A previous study reported that GSH and oxidized glutathione (GSSG) are not substrates for murine GGT5 (PubMed:9774450). However, this result contrasts with two studies reported that GSH is indeed a substrate for GGT5 (By similarity).|||Belongs to the gamma-glutamyltransferase family.|||Cleaved by autocatalysis into a large and a small subunit.|||Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione-S-conjugate (By similarity). Converts leukotriene C4 (LTC4), a glutathione-S-conjugate, to leukotriene D4 (LTD4) (PubMed:9774450, PubMed:11463821, PubMed:12163373). Does not cleaves gamma-glutamyl compounds such as gamma-glutamyl leucine. May also catalyze a transpeptidation reaction in addition to the hydrolysis reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Acts as a negative regulator of geranylgeranyl glutathione bioactivity by cleaving off its gamma-glutamyl group, playing a role in adaptive immune responses (By similarity).|||Deficient mice shown no obvious phenotype but in most organs they have only 10% of the wild-type levels of gamma-glutamyl leukotrienase activity (PubMed:11463821). Mice deficient in GGT5 have significantly more airway hyper-reactivity in a model of experimental asthma (PubMed:12163373).|||Glycosylated.|||Heterodimer composed of the light and heavy chains (PubMed:12163373). The active site is located in the light chain (By similarity).|||Inhibited by serine-borate.|||Membrane|||Very low expression.|||Very low level of expression. Detected in spleen lymphocytes, medullary and paracortical thymic lymphocytes, lung interstitial cells, bronchial epithelium, proximal tubules in kidney, crypt cells in small intestine, neurons in brain stem and cerebral cortex and in Purkinje cells. http://togogenome.org/gene/10090:Itgbl1 ^@ http://purl.uniprot.org/uniprot/Q8VDV0 ^@ Domain|||Subcellular Location Annotation ^@ Contains ten tandem EGF-like repeats strikingly similar to those found in the cysteine rich 'stalk-like' structure of integrin beta-subunits.|||Secreted http://togogenome.org/gene/10090:Ahsp ^@ http://purl.uniprot.org/uniprot/Q9CY02 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation.|||Belongs to the AHSP family.|||By GATA-1 during erythroid maturation.|||Cytoplasm|||Expressed in spleen, bone marrow, and blood, with highest levels in bone marrow.|||Monomer. Forms a heterodimer with free alpha-hemoglobin. Does not bind beta-hemoglobin nor alpha(2)beta(2) hemoglobin A. http://togogenome.org/gene/10090:Dnajc21 ^@ http://purl.uniprot.org/uniprot/E9Q8D0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with HSPA8, PA2G4 and ZNF622.|||May act as a co-chaperone for HSP70. May play a role in ribosomal RNA (rRNA) biogenesis, possibly in the maturation of the 60S subunit. Binds the precursor 45S rRNA.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Ddx55 ^@ http://purl.uniprot.org/uniprot/E9Q9T6|||http://purl.uniprot.org/uniprot/Q6ZPL9|||http://purl.uniprot.org/uniprot/Q810A4 ^@ Domain|||Function|||Similarity ^@ Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX55/SPB4 subfamily.|||Probable ATP-binding RNA helicase.|||RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis. http://togogenome.org/gene/10090:Pisd ^@ http://purl.uniprot.org/uniprot/E9PX91|||http://purl.uniprot.org/uniprot/Q505E1|||http://purl.uniprot.org/uniprot/Q8BSF4 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphatidylserine decarboxylase family. PSD-B subfamily. Eukaryotic type I sub-subfamily.|||Binds 1 pyruvoyl group covalently per subunit.|||Catalyzes the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer). Plays a central role in phospholipid metabolism and in the interorganelle trafficking of phosphatidylserine.|||Catalyzes the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer). Plays a central role in phospholipid metabolism and in the interorganelle trafficking of phosphatidylserine. May be involved in lipid droplet biogenesis at the endoplasmic reticulum membrane (By similarity).|||Cytoplasm|||Expressed during development in tissues rich in mitochondria, such as heart. In liver, low expression level observed in embryos and newborn animals increases 10-fold in adult.|||Heterodimer of a large membrane-associated beta subunit and a small pyruvoyl-containing alpha subunit.|||Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The autoendoproteolytic cleavage occurs by a canonical serine protease mechanism, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl prosthetic group on the alpha chain. During this reaction, the Ser that is part of the protease active site of the proenzyme becomes the pyruvoyl prosthetic group, which constitutes an essential element of the active site of the mature decarboxylase.|||Lipid droplet|||Mitochondrion inner membrane|||Mutant embryos die in utero between 8 and 10 dpc. They exhibit large numbers of aberrantly shaped mitochondria. In mutant embryonic fibroblasts, fragmented, rounded mitochondria of irregular diameter are widely dispersed throughout the cell rather than being concentrated around the nucleus.|||Widely expressed, with highest levels in testis, including Sertoli cells, followed by liver. http://togogenome.org/gene/10090:Zfp524 ^@ http://purl.uniprot.org/uniprot/Q9D0B1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Arhgap5 ^@ http://purl.uniprot.org/uniprot/P97393 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in spinal cord, cerebellum, kidney, testis and lung.|||GTPase-activating protein for Rho family members.|||May interact with RASA1/p120GAP.|||The pG1 pseudoGTPase domain does not bind GTP. http://togogenome.org/gene/10090:Mmrn1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SVL8|||http://purl.uniprot.org/uniprot/B2RPV6|||http://purl.uniprot.org/uniprot/G3UVV6 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Carrier protein for platelet (but not plasma) factor V/Va. Plays a role in the storage and stabilization of factor V in platelets. Upon release following platelet activation, may limit platelet and plasma factor Va-dependent thrombin generation. Ligand for integrin alpha-IIb/beta-3 and integrin alpha-V/beta-3 on activated platelets, and may function as an extracellular matrix or adhesive protein (By similarity).|||Extensively N-glycosylated.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Multimeric. Composed of varying sized, disulfide-linked multimers, the smallest of which is a homotrimer. Proteolysis of the promultimerin in the N-terminal region, leads to the mature p155 form that is stored in platelets. Interacts with factor V/Va (By similarity).|||Secreted http://togogenome.org/gene/10090:Cdkl2 ^@ http://purl.uniprot.org/uniprot/Q9QUK0 ^@ Domain|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Expressed in testis, kidney, lung and brain.|||Nucleus|||The [NKR]KIAxRE motif seems to be a cyclin-binding region. http://togogenome.org/gene/10090:Garin1b ^@ http://purl.uniprot.org/uniprot/Q3UZD7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GARIN family.|||Expressed from day 21, around when spermiogenesis occurs (PubMed:34714330). Expression dramatically increases at the mid-round spermatid stage (steps 4-6) (PubMed:34714330).|||Expressed in testis (at protein level).|||Golgi apparatus|||Mutant males are sterile (PubMed:34714330). Spermatozoa from mutant mice showed abnormal head shapes with an abnormal swollen acrosome morphology and impaired acrosome reaction (PubMed:34714330).|||RAB2B effector protein required for accurate acrosome formation and normal male fertility (PubMed:34714330). In complex with RAB2A/RAB2B, seems to suppress excessive vesicle trafficking during acrosome formation (PubMed:34714330). http://togogenome.org/gene/10090:Or4d2 ^@ http://purl.uniprot.org/uniprot/Q5SW49 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dnmbp ^@ http://purl.uniprot.org/uniprot/A0A0R4J055|||http://purl.uniprot.org/uniprot/A0A1D5RLL6|||http://purl.uniprot.org/uniprot/Q6TXD4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds DNM1 via its N-terminal SH3 domains (PubMed:14506234). The C-terminal SH3 domain binds a complex containing actin, tubulin, Hsp70 and actin-regulatory proteins, such as ENAH, EVL, WIRE, CR16, WAVE1 and NAP1L1 (PubMed:14506234). Interacts with FASLG (By similarity). Interacts (via SH3 domain 6) with WASL (By similarity). Interacts (via SH3 domain 6) interacts with ENAH (By similarity). Interacts (via C-terminal domain) with TJP1; required for the apical cell-cell junction localization of DNMBP (By similarity).|||Cell junction|||Cytoplasm|||Golgi stack|||Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions in epithelial cells (By similarity). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (By similarity). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (PubMed:14506234).|||Synapse|||cytoskeleton http://togogenome.org/gene/10090:Clrn2 ^@ http://purl.uniprot.org/uniprot/B2RVW2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the clarin family.|||Detected in inner ear, particularly in hair bundles of auditory hair cells and is enriched in apical stereocilia. Detected in eye, but not in brain or muscle.|||Expression in the cochlea is stable from late embryonic stages to P12 (the onset of hearing in mice), but thereafter increases.|||Mice homozygous for an ENU-induced allele exhibit an early-onset, progressive hearing loss, with a lack of fast-graded voltage responses. These mice harbor an early truncating nonsense variant (Trp4Ter). By postnatal days 6 (P6), mutants do not exhibit any gross patterning defects, or differences in the overall number of outer hair cells (OHC) and inner hair cells (IHC) bundles compared to controls. However, despite normal shape organization, these mice shown a progressive reduction in height of the middle and shortest row stereocilia, which is evident first in OHCs by P8, and then later in IHCs at P16.|||Plays a key role to hearing function. Required for normal organization and maintenance of the stereocilia bundle and for mechano-electrical transduction.|||stereocilium membrane http://togogenome.org/gene/10090:Spin4 ^@ http://purl.uniprot.org/uniprot/Q8K1L2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the SPIN/STSY family.|||Exhibits H3K4me3-binding activity.|||Interacts with C11orf84/SPINDOC. http://togogenome.org/gene/10090:Or51f23 ^@ http://purl.uniprot.org/uniprot/E9PWA8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd68 ^@ http://purl.uniprot.org/uniprot/P31996 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LAMP family.|||CD68 is a commonly used marker for macrophages. However, a number of studies in human have shown that CD68 antibodies react with other hematopoietic and non-hematopoietic cell types, suggesting that CD68 may not be a macrophage-specific antigen.|||Cell membrane|||Could play a role in phagocytic activities of tissue macrophages, both in intracellular lysosomal metabolism and extracellular cell-cell and cell-pathogen interactions. Binds to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular sites. Rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane may allow macrophages to crawl over selectin-bearing substrates or other cells.|||Endosome membrane|||Expressed in tissue macrophages and to a lesser extent in dendritic cells.|||Lysosome membrane|||N- and O-glycosylated. http://togogenome.org/gene/10090:Traf6 ^@ http://purl.uniprot.org/uniprot/P70196 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abrogation of IL-1-induced activation of NF-kappa-B, MAPK8/JNK and MAPK14/p38. Animals appear normal at birth but become smaller after one week. Show runting, failure of tooth eruption and die after three weeks. Exhibit severe osteopetrosis, thymic atrophy, lymph node deficiency, splenomegaly, and have alopecia and lack sweat glands.|||Belongs to the TNF receptor-associated factor family. A subfamily.|||Cytoplasm|||E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 (PubMed:15322147, PubMed:17633018). Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation (By similarity). Leads to the activation of NF-kappa-B and JUN. Seems to also play a role in dendritic cells (DCs) maturation and/or activation (PubMed:14499111). Represses c-Myb-mediated transactivation, in B-lymphocytes (By similarity). Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor (PubMed:10421844, PubMed:10215628). Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation (PubMed:10421844, PubMed:17092936). Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production (PubMed:12881420). Participates also in the TCR signaling by ubiquitinating LAT (By similarity).|||Highly expressed in brain, lung, liver, skeletal muscle, and kidney; lower expression in heart, spleen, and testis.|||Homotrimer (By similarity). Homooligomer (By similarity). N-terminal region is dimeric while C-terminal region is trimeric; maybe providing a mode of oligomerization. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Binds to TNFRSF5/CD40 and TNFRSF11A/RANK (By similarity). Associates with NGFR, TNFRSF17, IRAK2, IRAK3, PELI2, PELI3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting protein TRIP and TNF receptor associated protein TDP2. Binds UBE2V1. Interacts with MAVS/IPS1. Interacts with TAX1BP1; this interaction mediates deubiquitination of TRAF6 and inhibition of NF-kappa-B activation (By similarity). Interacts with IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary complex with SQSTM1 and PRKCZ. Interacts with IL1RL1. Interacts with AJUBA (By similarity). Interacts with TRAFD1. Interacts with TICAM2. Interacts with ZFAND5. Interacts with ARRB1 and ARRB2 (By similarity). Interacts with MAP3K7 and TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and AKT3. Interacts (via TRAF domains) with NUMBL (via C-terminal) (By similarity). Interacts (via TRAF domains) with DYNC2I2 (via WD domains). Interacts with RBCK1 (By similarity). Interacts with LIMD1 (via LIM domains). Interacts with RSAD2/viperin. Interacts with IFIT3 (via N-terminus) (By similarity). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain). Interacts with CARD14 (By similarity). Interacts with CD40 and MAP3K8; the interaction is required for ERK activation. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (By similarity). Interacts with TANK; this interaction increases in response to DNA damage (By similarity). Interacts with USP10; this interaction increases in response to DNA damage (By similarity). Interacts with ZC3H12A; this interaction increases in response to DNA damage and is stimulated by TANK (By similarity). Interacts with WDFY3 (PubMed:27330028). Interacts with TRIM13 (By similarity). Interacts with GPS2 (PubMed:22424771). Interacts (via C-terminus) with SASH1 (By similarity). Interacts with LRRC19 (By similarity). Interacts with IL17RA and TRAF3IP2. Interacts with TOMM70 (By similarity). Interacts with AMBRA1; interaction is required to mediate 'Lys-63'-linked ubiquitination of ULK1 (By similarity). Interacts with CRBN; this interaction inhibits TLR4-mediated signaling by preventing TRAF6-mediated ubiquitination of ECSIT (By similarity).|||Lipid droplet|||Nucleus|||Polyubiquitinated on Lys-124 by TRAF3IP2; after cell stimulation with IL17A (By similarity). Polyubiquitinated; after cell stimulation with IL1B or TGFB. This ligand-induced cell stimulation leads to dimerization/oligomerization of TRAF6 molecules, followed by auto-ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 activation. This 'Lys-63' site-specific poly-ubiquitination appears to be associated with the activation of signaling molecules. Endogenous autoubiquitination occurs only for the cytoplasmic form. Deubiquitinated by USP10 in a TANK-dependent manner, leading to the negative regulation of NF-kappa-B signaling upon DNA damage. LRRC19 induces 'Lys-63' ubiquitination (PubMed:25026888). Ubiquitinated at Lys-327 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:23542741).|||Sumoylated on Lys-124, Lys-142 and Lys-461 with SUMO1.|||The MATH/TRAF domain binds to receptor cytoplasmic domains.|||The coiled coil domain mediates homo- and hetero-oligomerization.|||cell cortex http://togogenome.org/gene/10090:Or7a36 ^@ http://purl.uniprot.org/uniprot/Q8VGX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnfrsf11b ^@ http://purl.uniprot.org/uniprot/O08712|||http://purl.uniprot.org/uniprot/Q3UK97 ^@ Caution|||Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis.|||Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.|||Detected in embryo at high levels on day 7, whereas expression decreases at day 11 and increases from day 15 to 17. On day 15 found in developing bone primordia, brachiocephalic artery and ductus arteriosus, left main bronchus, abdominal aorta and midgut.|||Highly expressed in liver, lung, stomach, intestines and calvaria. Highly expressed in decidua and placenta, and in embryo.|||Homodimer.|||Homodimer. Interacts with TNFSF10 and TNFSF11.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||Up-regulated by TGF-beta and estrogens. Down-regulated by 1,25-dihdroxyvitamin D3 and parathyroid hormone. http://togogenome.org/gene/10090:Atp5pb ^@ http://purl.uniprot.org/uniprot/Q5I0W0|||http://purl.uniprot.org/uniprot/Q9CQQ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ATPase B chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) has three main subunits: a, b and c.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Hspa12a ^@ http://purl.uniprot.org/uniprot/Q8K0U4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein for SORL1, but not SORT1. Delays SORL1 internalization and affects SORL1 subcellular localization.|||Belongs to the heat shock protein 70 family.|||Cytoplasm|||Expressed most strongly in brain, kidney and heart with little or no expression in other tissues (PubMed:12552099). In the brain, expressed in glial cells, including astrocytes (at protein level) (PubMed:30679749). In the aorta, preferentially expressed in lesions (PubMed:12552099).|||Interacts with SORL1 (via cytosolic C-terminus); this interaction affects SORL1 internalization and subcellular localization.|||Nucleus http://togogenome.org/gene/10090:Neurl4 ^@ http://purl.uniprot.org/uniprot/Q5NCX5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with CCP110; this interaction propmotes CCP110 ubiquitination and degradation via the proteasome pathway. Via its interaction with CCP110, may indirectly interact with CEP97. Interacts with the E3 ubiquitin-protein ligase HERC2 and UBE3A. May interact with MAPK6 and hence mediate MAPK6 interaction with UBE3A. Interaction with UBE3A may be indirect and mediated by HERC2 (By similarity).|||Promotes CCP110 ubiquitination and proteasome-dependent degradation. By counteracting accumulation of CP110, maintains normal centriolar homeostasis and preventing formation of ectopic microtubular organizing centers (By similarity).|||Ubiquitinated; undergoes HERC2-dependent 'Lys-48' ubiquitination. This ubiquitination leads to proteasomal degradation (By similarity).|||centriole http://togogenome.org/gene/10090:Rfk ^@ http://purl.uniprot.org/uniprot/Q8CFV9 ^@ Cofactor|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the phosphorylation of riboflavin (vitamin B2) to form flavin-mononucleotide (FMN), hence rate-limiting enzyme in the synthesis of FAD. Essential for TNF-induced reactive oxygen species (ROS) production. Through its interaction with both TNFRSF1A and CYBA, physically and functionally couples TNFRSF1A to NADPH oxidase. TNF-activation of RFK may enhance the incorporation of FAD in NADPH oxidase, a critical step for the assembly and activation of NADPH oxidase (By similarity).|||Cytoplasm|||Monomer (By similarity). Directly interacts with TNFRSF1A death domain; this interaction may be supported by TRADD (PubMed:19641494). In the absence of TNFRSF1A, interacts with TRADD (PubMed:19641494). Independently of TNFRSF1A, interacts with the NADPH oxidase subunit CYBA (PubMed:19641494).|||Mutant embryos die in utero before 7.5 dpc.|||Zinc or magnesium. http://togogenome.org/gene/10090:Raly ^@ http://purl.uniprot.org/uniprot/Q3U3F6|||http://purl.uniprot.org/uniprot/Q64012 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM HNRPC family. RALY subfamily.|||Defects in Raly are the cause of lethal yellow mutation (A(y)), a dominant allele that cause embryonic lethality when homozygous, and pleiotropic effects when heterozygous, including yellow pelage, obesity, non-insulin dependent diabetes and increased tumor susceptibility. A(y) is due to a 170 kb deletion that removes all but the promoter and non-coding first exon of Raly and links them to the ASIP/Agouti gene.|||Expressed in the unfertilized egg, in the blastocyst, as well as in the developing embryo and fetus. Expressed in developing skin.|||Identified in the spliceosome C complex. Interacts (through its RNA-binding domain) with FUS (through its RNA-binding domain); both are components of the same RNPs.|||Nucleus|||RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver (PubMed:27251289). Binds the lipid-responsive non-coding RNA LeXis and is required for LeXis-mediated effect on cholesterogenesis (PubMed:27251289). May be a heterogeneous nuclear ribonucleoprotein (hnRNP) (By similarity).|||Widely expressed. Expressed in brain, testis, lung, spleen and kidney. Weakly expressed in liver. http://togogenome.org/gene/10090:Pcnp ^@ http://purl.uniprot.org/uniprot/Q3KQH9|||http://purl.uniprot.org/uniprot/Q3UCC5|||http://purl.uniprot.org/uniprot/Q6P8I4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with UHRF2/NIRF.|||May be involved in cell cycle regulation.|||N-terminally acetylated in a HYPK-dependent manner by the NatA acetyltransferase complex which is composed of NAA10 and NAA15.|||Nucleus|||Ubiquitinated; mediated by UHRF2 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Snrnp70 ^@ http://purl.uniprot.org/uniprot/Q62376 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (By similarity). Interacts with SCNM1 (PubMed:17656373). Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2. Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRNP70, SNRPA1, SRRM1 and TRA2B/SFRS10. Interacts with dephosphorylated SFRS13A and SFPQ. Interacts with NUDT21/CPSF5, CPSF6, SCAF11, and ZRANB2. Interacts with GEMIN5 (By similarity). Interacts with FUS (By similarity).|||Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. SNRNP70 binds to the loop I region of U1-snRNA.|||Extensively phosphorylated on serine residues in the C-terminal region.|||Nucleus speckle|||The RRM domain mediates interaction with U1 RNA.|||Truncated isoforms that lack the RRM domain cannot bind U1-snRNA.|||nucleoplasm http://togogenome.org/gene/10090:Gtpbp8 ^@ http://purl.uniprot.org/uniprot/Q9CY28 ^@ Similarity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngB GTPase family. http://togogenome.org/gene/10090:Ppp1r10 ^@ http://purl.uniprot.org/uniprot/Q80W00 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1CC (By similarity). Interacts with PPP1CA, WDR82 and TOX4.|||Nucleus|||Phosphorylated on Thr-398 by PKA within the region necessary for interaction with PPP1CA.|||Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers. http://togogenome.org/gene/10090:Cckbr ^@ http://purl.uniprot.org/uniprot/P56481|||http://purl.uniprot.org/uniprot/Q3ZB46 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for gastrin and cholecystokinin. The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity).|||Receptor for gastrin and cholecystokinin. The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Echdc1 ^@ http://purl.uniprot.org/uniprot/Q9D9V3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||Decarboxylates ethylmalonyl-CoA, a potentially toxic metabolite, to form butyryl-CoA, suggesting it might be involved in metabolite proofreading. Acts preferentially on (S)-ethylmalonyl-CoA but has also some activity on the (R)-isomer. Also has methylmalonyl-CoA decarboxylase activity at lower level.|||cytosol http://togogenome.org/gene/10090:Thsd7a ^@ http://purl.uniprot.org/uniprot/Q69ZU6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Cell projection|||Detected on kidney podocytes along the glomerular capillary wall (at protein level).|||Extensively N-glycosylated.|||Plays a role in actin cytoskeleton rearrangement.|||Proteolytic cleavage in the extracellular region generates a 210 kDa soluble form.|||Secreted|||Sequence analysis combined with the expression of constructs corresponding each to two or three adjacent TSP type-1 domains suggests the presence of 21 TSP type-1 domains; not all of these are detected by standard bioinformatic tools.|||The soluble form promotes endothelial cell migration and filopodia formation during sprouting angiogenesis via a FAK-dependent mechanism. http://togogenome.org/gene/10090:Tas2r119 ^@ http://purl.uniprot.org/uniprot/A2VCK4|||http://purl.uniprot.org/uniprot/Q9JKT2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in 15% taste bud cells in circumvallate and foliate papillae but only in 2% in fungiform papillae. Expressed in the gastro and duodenal tissue. Not expressed in colon, liver, heart and kidney.|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Mycn ^@ http://purl.uniprot.org/uniprot/P03966|||http://purl.uniprot.org/uniprot/Q3UII1 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with KDM5A, KDM5B and HUWE1. Interacts with MYCNOS. Interacts with AURKA; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to unphosphorylated MYCN. Interacts with FBXW7; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN.|||Expressed in the proliferating cells of the developing CNS and the epidermis. In the spinal cord at embryonic days 10.5, 11.5 and 12.5 dpc, expressed in the proliferating cells of the ventricular zone of the neural tube and is expressed at reduced levels in the intermediate zone. At 14.5 dpc, found in regions containing differentiating post-mitotic neurons. In the developing epidermis at 17 dpc, expression is restricted to primary hair germ cells only.|||Nucleus|||Phosphorylated by GSK3-beta which may promote its degradation. Phosphorylated by AURKA.|||Positively regulates the transcription of MYCNOS in neuroblastoma cells.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Klra1 ^@ http://purl.uniprot.org/uniprot/Q8MHR8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ehf ^@ http://purl.uniprot.org/uniprot/O70273 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ETS family.|||Highly expressed in kidney and lung, weakly in skeletal muscle, heart, and liver, and not detected in brain, spleen or testis.|||Nucleus|||The PNT domain acts as a transcriptional activator.|||Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes, and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter (By similarity). http://togogenome.org/gene/10090:Prdx4 ^@ http://purl.uniprot.org/uniprot/O08807 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.|||Cytoplasm|||Endoplasmic reticulum|||Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer.|||The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.|||The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) and sulphonic acid (C(P)-SO3H) instead of its condensation to a disulfide bond.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events (PubMed:11229364). Regulates the activation of NF-kappa-B in the cytosol by a modulation of I-kappa-B-alpha phosphorylation (By similarity). http://togogenome.org/gene/10090:H2ac13 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Eid3 ^@ http://purl.uniprot.org/uniprot/Q3V124 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a repressor of nuclear receptor-dependent transcription possibly by interfering with CREBBP-dependent coactivation. May function as a coinhibitor of other CREBBP/EP300-dependent transcription factors (By similarity).|||Belongs to the NSE4 family.|||Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3; EID3 seems to be a testis-specific subunit. NSMCE1, NSMCE4A or EID3 and NSMCE3 probably form a subcomplex that bridges the head domains of the SMC5:SMC6 heterodimer. Homodimer, and heterodimer with EID2. Interacts with the C-terminal region of CREBBP (By similarity).|||Cytoplasm|||Nucleus|||Tissue-specific component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components (By similarity).|||telomere http://togogenome.org/gene/10090:Asic5 ^@ http://purl.uniprot.org/uniprot/D3Z0S5|||http://purl.uniprot.org/uniprot/Q9R0Y1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family.|||Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC5 subfamily.|||Cation channel that gives rise to very low constitutive currents in the absence of activation. The activated channel exhibits selectivity for sodium and lithium, and is inhibited by amiloride (By similarity).|||Cell membrane|||Detected in cerebellum, brainstem, kidney, liver, hepatocytes, lung, intestine and embryo. In the cerebellum. restricted to interneurons in the granular layer, specifically in GRM1-expressing unipolar brush cells of the vestibulocerebellum.|||Homotrimer or heterotrimer with other ASIC proteins.|||Membrane http://togogenome.org/gene/10090:Ezr ^@ http://purl.uniprot.org/uniprot/P26040|||http://purl.uniprot.org/uniprot/Q3UL48|||http://purl.uniprot.org/uniprot/Q4KML7|||http://purl.uniprot.org/uniprot/Q8CBU4 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding.|||Apical cell membrane|||Cell membrane|||Cell projection|||Detected in eye lens fiber cells (PubMed:21745462). Expressed in cerebrum and cerebellum (at protein level) (PubMed:15797715). Component of the microvilli of intestinal epithelial cells.|||Detected in whole embryo from 5 dpc with highest expression at 8, 11, 12, and 18 dpc. Expressed at 18 dpc in brain, a clear reduction occurs after birth followed by a transient increase around 2 weeks to 1 month. Hardly detected in adult brain.|||Has three main structural domains: an N-terminal FERM domain, a central alpha-helical domain and a C-terminal actin-binding domain.|||Interacts with PALS1 and NHERF2. Found in a complex with EZR, PODXL and NHERF2 (By similarity). Interacts with MCC, PLEKHG6, PODXL, SCYL3/PACE1, NHERF1 and TMEM8B. Interacts (when phosphorylated) with FES/FPS. Interacts with dimeric S100P, the interaction may be activating through unmasking of F-actin binding sites (By similarity). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (PubMed:21745462). Detected in a complex composed of at least EZR, AHNAK, PPL and PRX (By similarity). Interacts with PDPN (via cytoplasmic domain); activates RHOA and promotes epithelial-mesenchymal transition (By similarity). Interacts with SPN/CD43 cytoplasmic tail (PubMed:9472040, PubMed:21289089). Interacts with CD44 and ICAM2 (PubMed:9472040). Interacts with SLC9A3; interaction targets SLC9A3 to the apical membrane (By similarity). Interacts with SLC9A1; regulates interactions of SLC9A1 with cytoskeletal and promotes stress fiber formation (By similarity).|||Membrane|||Phosphorylated by tyrosine-protein kinases. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding.|||Probably involved in connections of major cytoskeletal structures to the plasma membrane. In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis (By similarity).|||S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.|||The FERM domain is organized in a clover-shaped structure that comprises three subdomains identified as F1 (residues 2-82), F2 (residues 96-198), and F3 (residues 204-296). In the active form, the subdomain F3 adopts two mutually exclusive conformational isomers where a row of four phenylalanine side chains (Phe250, Phe255, Phe267 and Phe269) must point in the same direction. In the autoinhibited form, the F3 subdomain interacts with the C-terminal domain (residues 516-586) and stabilizes the structure, selecting only one possible arrangement of phenylalanine side chains. The FERM domain mediates binding to membrane lipids and signaling molecules.|||The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.|||The central alpha-helical domain is composed of two alpha helices (residues 326-406 and 417-466) connected by a linker. It protrudes from the FERM domain forming a coiled coil structure where the linker can have either a loop or a helix conformation. The monomer is predicted to form an intra-molecular helix-loop-helix coiled coil structure. Whereas the dimer adopts an elongated dumbbell-shaped configuration where continuous alpha helices from each protomer are organized in a antiparallel coiled coil structure that connect FERM:C-terminal domain swapped complex at each end. The dimer is predicted to link actin filaments parallel to the plasma membrane.|||cell cortex|||cytoskeleton|||microvillus|||microvillus membrane|||ruffle membrane http://togogenome.org/gene/10090:Ahsa2 ^@ http://purl.uniprot.org/uniprot/Q8N9S3 ^@ Function|||Similarity ^@ Belongs to the AHA1 family.|||Co-chaperone that stimulates HSP90 ATPase activity. http://togogenome.org/gene/10090:Ggact ^@ http://purl.uniprot.org/uniprot/Q923B0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the gamma-glutamylcyclotransferase family.|||Contributes to degradation of proteins cross-linked by transglutaminases by degrading the cross-link between a lysine and a glutamic acid residue. Catalyzes the formation of 5-oxo-L-proline from L-gamma-glutamyl-L-epsilon-lysine. Inactive with L-gamma-glutamyl-alpha-amino acid substrates such as L-gamma-glutamyl-L-alpha-cysteine and L-gamma-glutamyl-L-alpha-alanine.|||Monomer. http://togogenome.org/gene/10090:Tmeff1 ^@ http://purl.uniprot.org/uniprot/Q6PFE7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc, highly expressed in the first branchial arch, somites, splanchnic mesoderm and ventral foregut epithelium. At 9.5 dpc, highly expressed in motor neurons and superficial neurons from the neural tube, and in the dorsal part of diencephalon and mesencephalon. At 11.5 dpc and 12.5 dpc, expressed in limbs. At 15.5 dpc, highly expressed in brain and spinal cord.|||Belongs to the tomoregulin family.|||Cell membrane|||Expressed in brain, neurointermediate lobe, pars distalis, pancreas, ovary and testis.|||May inhibit NODAL and BMP signaling during neural patterning.|||May interact with ST14. http://togogenome.org/gene/10090:Ppp3cb ^@ http://purl.uniprot.org/uniprot/A0A6B9EQU3|||http://purl.uniprot.org/uniprot/E0CZ78|||http://purl.uniprot.org/uniprot/G3X8U7|||http://purl.uniprot.org/uniprot/P48453 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A.|||Belongs to the PPP phosphatase family. PP-2B subfamily.|||Binds 1 Fe(3+) ion per subunit.|||Binds 1 zinc ion per subunit.|||Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (By similarity). Dephosphorylates TFEB in response to lysosomal Ca(2+) release, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (By similarity). Dephosphorylates and activates transcription factor NFATC1 (By similarity). Dephosphorylates and inactivates transcription factor ELK1 (By similarity). Dephosphorylates DARPP32 (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (PubMed:26029823). May play a role in skeletal muscle fiber type specification (PubMed:12773574).|||Cytoplasm|||Expressed in kidney, in the thick ascending limb epithelium and in the collecting duct, but not in the distal convoluted tubule (at protein level) (PubMed:25967121, PubMed:15509543). Expressed in the brain and the bicep, tricep, soleus and gastrocnemius muscles (at protein level) (PubMed:12773574). Expressed in the salivary gland (at protein level) (PubMed:21435446). Expressed in hippocampal neuron nuclei and adjacent white matter tracts in the CA1 region of the hippocampus (at protein level) (PubMed:10200317).|||Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CB/calcineurin A, calcineurin B and calmodulin. Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B. Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+). Interacts with SLC12A1 (By similarity). Interacts with SORL1 (PubMed:25967121). Interacts with UNC119 (PubMed:31696965). Interacts with MAP3K14/NIK (via C-terminus and kinase domain) (PubMed:26029823). Interacts with TRAF3 (PubMed:26029823). Interacts with SPATA33 (via PQIIIT motif) (By similarity). Interacts with Irgm1; promoting its association with TFEB and TFEB dephosphorylation (By similarity).|||Knockout mice show reduced body weight, independent of changes in muscle weight (PubMed:12773574). Reduced slow and intermediate program type muscle fibers in the biceps, triceps and soleus (PubMed:12773574). Increased expression of fast program type muscle fibers in the soleus muscle (PubMed:12773574).|||Possible isomerization of Pro-318 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.|||The autoinhibitory domain prevents access to the catalytic site.|||The autoinhibitory segment prevents access to the substrate binding site.|||The poly-Pro domain may confer substrate specificity.|||Unlike for protein substrates, PPP3CB activity towards synthetic phosphatase substrate p-nitrophenyl phosphate (pNPP) is increased in presence of the immunosuppressant complex FKBP12-FK506. http://togogenome.org/gene/10090:Ddx41 ^@ http://purl.uniprot.org/uniprot/Q3UAC4|||http://purl.uniprot.org/uniprot/Q91VN6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX41 subfamily.|||Identified in the spliceosome C complex (By similarity). Interacts with ERCC6 (By similarity). Interacts with FAM50A (By similarity).|||Nucleus|||Probable ATP-dependent RNA helicase. Is required during post-transcriptional gene expression. May be involved in pre-mRNA splicing. http://togogenome.org/gene/10090:Gtf2ird2 ^@ http://purl.uniprot.org/uniprot/Q99NI3 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TFII-I family.|||No expression in embryo at 9.5 dpc and 10.5 dpc. Expressed in tooth epithelium at 13.5 dpc. At the early bell stage, Expression in preameloblasts and preodontoblasts.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Camkk1 ^@ http://purl.uniprot.org/uniprot/Q8VBY2 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Partially inhibited upon phosphorylation by PRCAKA/PKA (By similarity). May be regulated through phosphorylation by CAMK1 and CAMK4.|||Appears to be autophosphorylated in a Ca(2+)/calmodulin-dependent manner. Phosphorylated at multiple sites by PRCAKA/PKA. Phosphorylation of Ser-458 is blocked upon binding to Ca(2+)/calmodulin. In vitro, phosphorylated by CAMK1 and CAMK4 (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death.|||Cytoplasm|||Interacts with CAMK4 and calmodulin.|||Nucleus|||The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates.|||The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.|||Widely expressed. Differentially expressed in various brain regions. http://togogenome.org/gene/10090:Itpripl2 ^@ http://purl.uniprot.org/uniprot/Q3UV16 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ITPRIP family.|||Membrane http://togogenome.org/gene/10090:Ctps2 ^@ http://purl.uniprot.org/uniprot/P70303 ^@ Function|||Similarity ^@ Belongs to the CTP synthase family.|||Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides (By similarity). http://togogenome.org/gene/10090:Dnase1l3 ^@ http://purl.uniprot.org/uniprot/O55070 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DNase I family.|||Endoplasmic reticulum|||Expressed at high levels in liver, spleen and testes. Expressed at lower levels in heart, lungs, skeletal muscle and kidney. Not expressed in brain. Predominantly expressed in macrophages; at protein level. Secreted by mononuclear phagocytes.|||Expression is first detected at embryonic day 11, and higher amounts were detected at days 15 and 17.|||Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:15796714, PubMed:19154352, PubMed:12095301). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis. The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (PubMed:12050166, PubMed:15167901, PubMed:17218958, PubMed:24312463). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:15796714, PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (PubMed:29191910). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:29191910). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (PubMed:29191910).|||Inhibited by zinc. Inhibited by heparin and proteolysis by plasmin.|||Mice develop symptoms of the autoimmune disease systemic lupus erythematosus, characterized by high titers of anti-nuclear autoantibodies (ANA) directed against nucleosomes and double-stranded DNA, the deposition of immune complexes in glomeruli and full-blown glomerulonephritis (PubMed:27293190). Mice lacking both Dnase1 and Dnase1l3 show vascular occlusions following bacterial infection: defects are caused by the formation of intravascular neutrophil extracellular traps (NETs) clots that obstruct blood vessels and cause organ damage (PubMed:29191910).|||Nucleus|||Poly-ADP-ribosylated by PARP1. ADP-ribosylation negatively regulates enzymatic activity during apoptosis.|||Secreted http://togogenome.org/gene/10090:Gtf2e2 ^@ http://purl.uniprot.org/uniprot/Q3UIR2|||http://purl.uniprot.org/uniprot/Q9D902 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIE beta subunit family.|||Nucleus|||Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase (By similarity).|||Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase.|||Tetramer of two alpha and two beta chains.|||Tetramer of two alpha and two beta chains. Interacts with FACT subunit SUPT16H. Interacts with ATF7IP. Interacts with SND1. http://togogenome.org/gene/10090:Dnajc17 ^@ http://purl.uniprot.org/uniprot/Q91WT4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Embryonic lethal after the morula stage.|||Expressed in the thyroid gland.|||May negatively affect PAX8-induced thyroglobulin/TG transcription.|||Nucleus http://togogenome.org/gene/10090:Serpina3n ^@ http://purl.uniprot.org/uniprot/G3X8T9 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Rims4 ^@ http://purl.uniprot.org/uniprot/P60191 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds PPFIA3 (By similarity). Does not bind RAB3.|||Regulates synaptic membrane exocytosis.|||Synapse http://togogenome.org/gene/10090:Defb11 ^@ http://purl.uniprot.org/uniprot/Q8R2I7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Expressed in both adult and neonate brain, and very weakly in kidneys, epididymis, and testis.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Gm13278 ^@ http://purl.uniprot.org/uniprot/Q8CD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Atxn10 ^@ http://purl.uniprot.org/uniprot/P28658 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ataxin-10 family.|||Homooligomer (By similarity). Interacts with GNB2 (By similarity). Interacts with OGT. Interacts with IQCB1 (By similarity).|||In high cell density areas; cerebellar cortex, dentate gyrus, hippocampus, anterior olfactory nucleus, primary olfactory cortex.|||Necessary for the survival of cerebellar neurons. Induces neuritogenesis by activating the Ras-MAP kinase pathway. May play a role in the maintenance of a critical intracellular glycosylation level and homeostasis.|||perinuclear region http://togogenome.org/gene/10090:Elob ^@ http://purl.uniprot.org/uniprot/P62869 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. This includes the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. As part of a multisubunit ubiquitin ligase complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (By similarity). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (PubMed:33590678).|||Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit (PubMed:16498413). The elongin BC complex interacts with EPOP; leading to recruit the elongin BC complex to Polycomb group (PcG) target genes, thereby restricting excessive activity of the PRC2/EED-EZH2 complex (PubMed:27863225, PubMed:27863226). Part of E3 ubiquitin ligase complexes with CUL5 or CUL2, RBX1 and a substrate adapter protein that can be either ASB2, KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B, FEM1C, LRR1, SOCS1, SOCS5, ELOA, VHL or WSB1. Interacts with VHL. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with SPSB1. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component. May also interact with DCUN1D1, DCUN1D2, DCUN1D3 and DCUN1D5 (By similarity). As part of the Elongin BC E3 ubiquitin ligase complex; interacts with NRBP1 (By similarity). Component of the ECS(PCMTD1) complex with the substrate recognition subunit PCMTD1. Interacts with PCMTD1 (via the BC-box); the interaction is direct and stabilizes PCMTD1 (By similarity).|||Nucleus|||SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex) (By similarity). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells (PubMed:27863225, PubMed:27863226). http://togogenome.org/gene/10090:Abcc6 ^@ http://purl.uniprot.org/uniprot/Q9R1S7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of glutathione conjugates such as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS) (in vitro), and an anionic cyclopentapeptide endothelin antagonist, BQ-123. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (By similarity).|||Basal cell membrane|||Basolateral cell membrane|||Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Deficient mice spontaneously develop calcification and elastic fiber abnormalities in blood vessels and Bruch's membrane in the eye, whereas no clear changes were seen in the extracellular matrix of the skin. Calcification of blood vessels is most prominent in small arteries in the cortex of the kidney, but in old mice, it occurrs also in other organs and in the aorta and vena cava (PubMed:15888484). Mice have reduced inorganic pyrophosphate (PPi) plasma levels, a strong inhibitor of mineralization (PubMed:24277820).|||Glycosylated.|||Mediates the release of nucleoside triphosphates, predominantly ATP, into the circulation, where it is rapidly converted into AMP and the mineralization inhibitor inorganic pyrophosphate (PPi) by the ecto-enzyme ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), therefore playing a role in PPi homeostasis. http://togogenome.org/gene/10090:Sbp ^@ http://purl.uniprot.org/uniprot/P15501 ^@ Function|||Induction|||Similarity|||Tissue Specificity ^@ By androgens.|||Prostate.|||This protein seems to be functional equivalent to rat prostatic spermine-binding protein, which is involved in polyamine binding.|||To rat SBP. http://togogenome.org/gene/10090:Taok3 ^@ http://purl.uniprot.org/uniprot/Q8BYC6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Phosphorylation at Ser-324 by ATM following DNA damage is required for activation of the p38/MAPK14 stress-activated MAPK cascade. Phosphorylated by LRRK2 (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Self-associates. Interacts with ERN1 and TRAF2. Interaction with TRAF2 is facilitated under ER stress conditions, such as treatment with tunicamycin, and may promote TRAF2 phosphorylation (By similarity).|||Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of MAPK8/JNK cascade and diminishes its activation in response epidermal growth factor (EGF) (By similarity). http://togogenome.org/gene/10090:Trpm4 ^@ http://purl.uniprot.org/uniprot/A0A1B0GS49|||http://purl.uniprot.org/uniprot/Q7TN37 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM4 sub-subfamily.|||Calcium-activated non selective (CAN) cation channel that mediates membrane depolarization. While it is activated by increase in intracellular Ca(2+), it is impermeable to it (PubMed:17188667, PubMed:29211714). Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane. It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway (By similarity). Essential for the migration but not the maturation of dendritic cells (PubMed:18758465). Plays a role in keratinocyte differentiation (By similarity).|||Cell membrane|||Endoplasmic reticulum|||Gating is voltage-dependent and repressed by decavanadate. Calmodulin-binding confers the Ca(2+) sensitivity. ATP is able to restore Ca(2+) sensitivity after desensitization. Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding strongly enhances activity, by increasing the channel's Ca(2+) sensitivity and shifting its voltage dependence of activation towards negative potentials. Activity is also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2) (By similarity). Inhibited by flufenamic acid and glibenclamide (PubMed:17188667).|||Golgi apparatus|||Homotetramer.|||Membrane|||Mice have fewer dendritic cells in lymphoid organs and impaired migration of dendritic cells is seen.|||Phosphorylation by PKC leads to increase the sensitivity to Ca(2+).|||Sino-atrial nodes (at protein level). Widely expressed.|||Sumoylated. Desumoylated by SENP1. http://togogenome.org/gene/10090:Il25 ^@ http://purl.uniprot.org/uniprot/Q8VHH8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-17 family.|||Cytokine produced by various cells such as eosinophils, T-helper type 2 (Th2) cells or epithelial cells that plays a role in internal safety of adaptive immune responses by regulating cytokine production (PubMed:35615348, PubMed:11754819). Promotes and augments T-helper type 2 responses locally or systemically (PubMed:35615348). Exerts its activity via its receptor composed of IL17RA and IL17RB for signal transduction (PubMed:18768888). In turn, stimulates the JAK2-STAT5A pathway and promotes the secretion of type-2 associated cytokines including IL4, IL9 and IL13. Induces also the release of IL8, and IL6 from eosinophils through the combined activation of MAPK and NF-kappa-B pathways. Inhibits the differentiation of T-helper (Th17) cells via the production of IL4, IL5 and IL13.|||Mice display mitigated inflammatory responses and Th2 responses in house dust mite/HDM-induced asthma model.|||Secreted http://togogenome.org/gene/10090:Krtap6-5 ^@ http://purl.uniprot.org/uniprot/Q925H3 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 6 family.|||Expression in skin and hair follicle is regulated by HOXC13 and by GATA3.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins.|||Strong expression in narrowly defined pattern restricted to the lower and middle cortical regions of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). http://togogenome.org/gene/10090:Mtfp1 ^@ http://purl.uniprot.org/uniprot/Q9CRB8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MTFP1 family.|||Involved in the mitochondrial division probably by regulating membrane fission. Loss-of-function leads to apoptosis (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Grm2 ^@ http://purl.uniprot.org/uniprot/Q14BI2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Detected in neurons in brain cortex (at protein level).|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.|||Interacts with TAMALIN (By similarity). Interacts with HTR2A.|||Synapse|||dendrite http://togogenome.org/gene/10090:Srgn ^@ http://purl.uniprot.org/uniprot/P13609 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the serglycin family.|||Binds to activated CD44 and to GZMB.|||By phorbol myristate acetate in T-lymphocytes. This induction is not inhibited by cyclosporine.|||Cytolytic granule|||Cytoplasmic granule|||Golgi apparatus|||Mice develop normally and are fertile but display mast cell granule and T-lymphocyte secretory granule defects. Granules are more amorphous than in the wild-type and show a less defined dense core formation. There is a lack of mast cell-specific protease activity although mRNAs for a variety of proteases are detected and storage of granzyme B is affected in T-lymphocytes. Neutrophil granules display a lack of neutrophil elastase and processing of MMP2 is abrogated. Macrophages show no major morphological defects.|||O-glycosylated; contains chondroitin sulfate and heparan sulfate.|||Plays a role in formation of mast cell secretory granules and mediates storage of various compounds in secretory vesicles. Required for storage of some proteases in both connective tissue and mucosal mast cells and for storage of granzyme B in T-lymphocytes. Plays a role in localizing neutrophil elastase in azurophil granules of neutrophils. Mediates processing of MMP2. Plays a role in cytotoxic cell granule-mediated apoptosis by forming a complex with granzyme B which is delivered to cells by perforin to induce apoptosis. Regulates the secretion of TNF-alpha and may also regulate protease secretion. Inhibits bone mineralization.|||extracellular space http://togogenome.org/gene/10090:Dph6 ^@ http://purl.uniprot.org/uniprot/Q9CQ28 ^@ Function|||Similarity ^@ Amidase that catalyzes the last step of diphthamide biosynthesis using ammonium and ATP. Diphthamide biosynthesis consists in the conversion of an L-histidine residue in the translation elongation factor 2 (EEF2) to diphthamide (By similarity).|||Belongs to the Diphthine--ammonia ligase family. http://togogenome.org/gene/10090:Ift81 ^@ http://purl.uniprot.org/uniprot/O35594 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT81 family.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT81, and IFT88 (PubMed:19253336, PubMed:23810713). Interacts with IFT74; the interaction is direct: within the IFT complex B, IFT74 and IFT81 mediate the transport of tubulin within the cilium. Interacts with tubulin; the interaction is direct (By similarity). Interacts with IFT57 and IFT70B (PubMed:23810713). Interacts with RABL2/RABL2A; binding is equal in the presence of GTP or GDP (PubMed:23055941). Interacts with IFT88 (PubMed:19253336). Interacts (via the IFT74/IFT81 heterodimer) with RABL2B (By similarity).|||Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds tubulin via its CH (calponin-homology)-like region. Required for ciliogenesis. Required for proper regulation of SHH signaling (By similarity). Plays an important role during spermatogenesis by modulating the assembly and elongation of the sperm flagella (PubMed:32233951).|||Cytoplasm|||Expressed predominantly in the testis.|||Expressed specifically in heart and suppressed specifically in ventricles, but not in auricles, of carnitine-deficient juvenile visceral steatosis (JVS) mice.|||First detected at postnatal day (PND) 8, its level increased dramatically from PND 16 to 42 (at protein level).|||Highly expressed in the testis (at protein level) (PubMed:32233951). Co-localizes with RABL2/RABL2A in the midpiece of elongated spermatids within the testis (at protein level) (PubMed:23055941).|||May be involved in cardiac hypertrophy caused by carnitine deficiency.|||May play a role in development of the testis and spermatogenesis.|||Mice show impaired spermiogenesis, abnormal sperm morphology and significantly reduced sperm number and motility (PubMed:32233951). In addition to oligozoospermia, spermatozoa show dysmorphic and non-functional flagella (PubMed:32233951).|||Poorly expressed in the testis 15 days after birth. Levels increase sharply between days 15 and 30 reaching a maximum by day 45 and the onset of spermatogenesis.|||The CH (calponin-homology)-like region shows high similarity to a CH (calponin-homology) domain and mediated binding to the globular domain of tubulin.|||cilium http://togogenome.org/gene/10090:Sem1 ^@ http://purl.uniprot.org/uniprot/P60897|||http://purl.uniprot.org/uniprot/Q3TV35 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DSS1/SEM1 family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including SEM1, a base containing 6 ATPases and few additional components. Belongs to the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (By similarity). Interacts with the C-terminal of BRCA2.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Component of the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3. The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and thus transcription-associated genomic instability. R-loop accumulation increases in SEM1-depleted cells.|||Nucleus http://togogenome.org/gene/10090:Gm6882 ^@ http://purl.uniprot.org/uniprot/J3KMT3 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Ankle1 ^@ http://purl.uniprot.org/uniprot/A8VU90 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endonuclease that probably plays a role in the DNA damage response and DNA repair.|||Interacts (via LEM domain) with BANF1; the interaction may favor BANF1 dimerization.|||Intron retention.|||No visible phenotype. No defect in T cell, B cell and erythrocyte development. Normal percentage of common myeloid precursors (CMP) and common lymphoid precursors (CLP) in the bone marrow.|||Nucleus|||Predominantly expressed in bone marrow, spleen, thymus, colon and ovary. Expressed also to a lesser extent in lymph nodes, liver and testis.|||The LEM domain is required for GIY-YIG domain-mediated DNA cleavage and induction of DNA damage response. http://togogenome.org/gene/10090:Ltf ^@ http://purl.uniprot.org/uniprot/P08071 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transferrin family.|||Cytoplasmic granule|||Lactotransferrin is a major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions. Has antimicrobial activity. Antimicrobial properties may include bacteriostasis, which is related to its ability to sequester free iron and thus inhibit microbial growth, as well as direct bactericidal properties leading to the release of lipopolysaccharides from the bacterial outer membrane. May have anabolic, differentiating and anti-apoptotic effects on osteoblasts and may also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth. May interfere with the lipopolysaccharide (LPS)-stimulated TLR4 signaling (By similarity).|||Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1 (By similarity).|||Secreted|||The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity. Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites.|||Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. http://togogenome.org/gene/10090:Phf6 ^@ http://purl.uniprot.org/uniprot/Q9D4J7 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc it is highly expressed in the embryonic central nervous system and at lower levels in other tissues. Very low levels present throughout the adult brain.|||Expression is high in the embryonic and early postnatal stages.|||Interacts with UBTF. Interacts with the NuRD complex component RBBP4 (via the nucleolar localization motif), the interaction mediates transcriptional repression activity (By similarity).|||Nucleus|||The PHD-type zinc finger 1 mediates both nucleolar localization and interaction with UBTF.|||The ePHD2 domain folds as an integrated structural module comprizing the C2HC pre-PHD-type 2 zinc finger and the PHD-type 2 zinc finger. It mediates non-specific binding to dsDNA, but doesn't bind histones in contrast to many PHD-type zinc fingers.|||Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription.|||kinetochore|||nucleolus http://togogenome.org/gene/10090:Prtg ^@ http://purl.uniprot.org/uniprot/Q2EY15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. DCC family.|||From mid-gastrulation to early somite stages, restricted to posterior neural plate and mesoderm with an anterior limit at the level of the rhombencephalon. Posterior restriction is progressively lost during somitogenesis. Expression is maintained in the neural tube and paraxial mesoderm during this process. As development proceeds, further restricted to the dorsal parts of the spinal cord and somites. In parallel, expression progresses caudally during axis elongation.|||May play a role in anteroposterior axis elongation.|||Membrane http://togogenome.org/gene/10090:Rbm27 ^@ http://purl.uniprot.org/uniprot/Q5SFM8 ^@ Domain|||Subcellular Location Annotation ^@ Cytoplasm|||Nucleus speckle|||The RRM domain mediates integration into cytospeckles. http://togogenome.org/gene/10090:Serpina3i ^@ http://purl.uniprot.org/uniprot/D3Z450 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Grm1 ^@ http://purl.uniprot.org/uniprot/P97772|||http://purl.uniprot.org/uniprot/Q3V0U2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Expressed in the striatum (at protein level).|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum (By. similarity). May function in the light response in the retina (PubMed:26427409).|||Homodimer; disulfide-linked (By similarity). The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with TAMALIN (By similarity). Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with SHIA1 (By similarity).|||Membrane http://togogenome.org/gene/10090:Cebpe ^@ http://purl.uniprot.org/uniprot/Q6PZD9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. C/EBP subfamily.|||Binds DNA as a homodimer and as a heterodimer. Can form stable heterodimers with CEBPA, CEBPB and CEBPD (By similarity). Interacts with GATA1 and SPI1 (By similarity). Interacts with SMARCD2 (By similarity).|||Nucleus|||Phosphorylated.|||Transcriptional activator. C/EBP are DNA-binding proteins that recognize two different motifs: the CCAAT homology common to many promoters and the enhanced core homology common to many enhancers. Required for the promyelocyte-myelocyte transition in myeloid differentiation. http://togogenome.org/gene/10090:Slc38a9 ^@ http://purl.uniprot.org/uniprot/Q8BGD6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated component of the Ragulator complex (composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5). Associated component of the Rag GTPases heterodimers (composed of RRAGA, RRAGB, RRAGC and RRAGD); this interaction is independent of the Ragulator complex but depends on the nucleotide loading state of the Rag GTPase heterodimer. Interacts with TM4SF5. Interacts with NPC1; this interaction inhibits cholesterol-mediated mTORC1 activation via its sterol transport activity.|||Belongs to the amino acid/polyamine transporter 2 family. SLC38A9 subfamily.|||Glycosylated.|||Late endosome membrane|||Lysosomal amino acid transporter involved in the activation of mTORC1 in response to amino acid levels. Probably acts as an amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. SLC38A9 mediates transport of amino acids with low capacity and specificity with a slight preference for polar amino acids. Acts as an arginine sensor. Following activation by arginine binding, mediates transport of L-glutamine, leucine and tyrosine with high efficiency, and is required for the efficient utilization of these amino acids after lysosomal protein degradation. However, the transport mechanism is not well defined and the role of sodium is not clear. Can disassemble the lysosomal folliculin complex (LFC), and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC. Acts as an cholesterol sensor that conveys increases in lysosomal cholesterol, leading to lysosomal recruitment and activation of mTORC1 via the Rag GTPases. Guanine exchange factor (GEF) that, upon arginine binding, stimulates GDP release from RRAGA and therefore activates the Rag GTPase heterodimer and the mTORC1 pathway in response to nutrient sufficiency.|||Lysosome membrane|||The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex. The cytosolic N-terminus part of the protein destabilizes the LFC and thereby triggers GAP activity of FLCN:FNIP2 toward RRAGC. The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer (By similarity). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (By similarity).|||the CARC and CRAC motifs mediate binding to cholesterol. http://togogenome.org/gene/10090:Or7a37 ^@ http://purl.uniprot.org/uniprot/Q8VGU8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Acsl1 ^@ http://purl.uniprot.org/uniprot/P41216 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (By similarity). Preferentially uses palmitoleate, oleate and linoleate (By similarity). Preferentially activates arachidonate than epoxyeicosatrienoic acids (EETs) or hydroxyeicosatrienoic acids (HETEs).|||Endoplasmic reticulum membrane|||Inhibited at high temperature and by arachidonate.|||Microsome membrane|||Mitochondrion outer membrane|||Peroxisome membrane http://togogenome.org/gene/10090:E2f3 ^@ http://purl.uniprot.org/uniprot/O35261|||http://purl.uniprot.org/uniprot/Q3TMJ9|||http://purl.uniprot.org/uniprot/Q3UZJ0|||http://purl.uniprot.org/uniprot/Q6PCM3|||http://purl.uniprot.org/uniprot/Q6ZQJ8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E2F/DP family.|||Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with TFDP1/Dp-1 to E2F sites. Interacts with retinoblastoma protein RB1 and related proteins (such as RBL1) that inhibit the E2F transactivation domain. Binds EAPP.|||In the developing nervous system, high levels expressed in both ventral and dorsal regions of the spinal cord from 13.5 dpc. Also expressed in dorsal root and cranial ganglia in 11.5-18.5 dpc embryos. Only low levels of expression in developing brain. In the developing retina (15.5 dpc), expression of E2F3 is localized to the ganglion cell layer. In other developing tissues, expressed in liver, lung and heart. Weak expression in developing kidney and skeletal muscle. Absent from the developing choroid plexus, thymus and developing skin. Low levels of expression in the developing intestinal epithelium and mesenchyme in 12.5-18.5 dpc embryos.|||Nucleus|||Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F3 binds specifically to RB1 in a cell-cycle dependent manner. Inhibits adipogenesis, probably through the repression of CEBPA binding to its target gene promoters (PubMed:20176812). http://togogenome.org/gene/10090:Lce1d ^@ http://purl.uniprot.org/uniprot/Q9D731 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Egflam ^@ http://purl.uniprot.org/uniprot/Q4VBE4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the apical side of the neuroblastic layer (NBL) of the retina at 14.5 dpc and 17.5 dpc. At 16.5 dpc, present in rib cartilage and hair follicle (at protein level).|||Expressed in the outer plexiform layer (first synaptic region) but not in the inner plexiform layer (second synaptic region) of the retina (at protein level). Strongly expressed in the photoreceptor layer of the retina. Moderately expressed in pineal gland and brain. Weakly expressed in lung and ovary.|||Interacts with DAG1 alpha-dystroglycan (PubMed:18641643). Interacts with GPR158 and GPR179; transsynaptic interaction is required for synaptic organization of photoreceptor cells (PubMed:30282023).|||Involved in both the retinal photoreceptor ribbon synapse formation and physiological functions of visual perception (PubMed:18641643, PubMed:18757743, PubMed:30282023). Plays a key role in the synaptic organization of photoreceptors by mediating transsynaptic interaction between alpha-dystroglycan and GPR179 on the postsynaptic membrane (PubMed:30282023). Necessary for proper bipolar dendritic tip apposition to the photoreceptor ribbon synapse (PubMed:18641643, PubMed:18757743, PubMed:30282023). Promotes matrix assembly and cell adhesiveness (PubMed:18641643, PubMed:18757743).|||No morphological abnormalities (PubMed:18641643). Knockout mice are viable and fertile (PubMed:18641643). However, the terminal of bipolar cells do not appose to the synapse terminals in the rod photoreceptor ribbon synapses (PubMed:18641643). The signal transmission from the rod photoreceptor to the rod bipolar cells is less sensitive and is delayed compared to the wild type mouse (PubMed:18641643). The signal transmission from cone photoreceptors to the cone bipolar cells is also impaired (PubMed:18641643). These mice show reduced visual function (PubMed:18641643). Impaired stability and postsynaptic targeting of GPR179 (PubMed:30282023).|||O-glycosylated; contains chondroitin sulfate and heparan sulfate.|||Presynaptic active zone|||Synaptic cleft|||extracellular matrix http://togogenome.org/gene/10090:Rbm34 ^@ http://purl.uniprot.org/uniprot/Q8C5L7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the RRM RBM34 family.|||nucleolus http://togogenome.org/gene/10090:Dock7 ^@ http://purl.uniprot.org/uniprot/A0A0U1RNK7|||http://purl.uniprot.org/uniprot/A2A9M5|||http://purl.uniprot.org/uniprot/E9PX48 ^@ Similarity ^@ Belongs to the DOCK family. http://togogenome.org/gene/10090:Chaf1b ^@ http://purl.uniprot.org/uniprot/Q9D0N7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat HIR1 family.|||Complex that is thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer (By similarity).|||Cytoplasm|||Nucleus|||Subunit of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A. CHAF1A binds directly to CHAF1B (By similarity). Interacts with histones H3.1, H3.2 and H3.1t (By similarity). http://togogenome.org/gene/10090:Baiap2l2 ^@ http://purl.uniprot.org/uniprot/Q80Y61 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell junction|||Cell membrane|||Cytoplasmic vesicle membrane|||Expressed in the epithelial layer of the intestine and in the kidney.|||Phosphoinositides-binding protein that induces the formation of planar or gently curved membrane structures. Binds to phosphoinositides, including to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) headgroups. There seems to be no clear preference for a specific phosphoinositide.|||The IMD domain consisting of an antiparallel dimer of three-helix bundles, featuring on one side a positively charged. The N-terminal alpha-helix inserts into the lipid bilayer. Also forms homodimers and homooligomers. The residue Trp-141 is essential for oligomer formation. http://togogenome.org/gene/10090:Kcne3 ^@ http://purl.uniprot.org/uniprot/Q545H9|||http://purl.uniprot.org/uniprot/Q9WTW2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Associated with KCNC4/Kv3.4 is proposed to form the subthreshold voltage-gated potassium channel in skeletal muscle and to establish the resting membrane potential (RMP) in muscle cells. Associated with KCNQ1/KCLQT1 may form the intestinal cAMP-stimulated potassium channel involved in chloride secretion that produces a current with nearly instantaneous activation with a linear current-voltage relationship.|||Belongs to the potassium channel KCNE family.|||Cell membrane|||Cytoplasm|||Interacts with KCNB1. Interacts with KCNC2 (By similarity). Associates with KCNC4/Kv3.4 (By similarity). Interacts with KCNQ1; produces a current with nearly instantaneous activation with a linear current-voltage relationship and alters membrane raft localization (By similarity).|||Membrane raft|||Perikaryon|||dendrite http://togogenome.org/gene/10090:Flnc ^@ http://purl.uniprot.org/uniprot/Q8VHX6 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the filamin family.|||Cytoplasm|||During myogenesis, isoform 1 is expressed the first day, then is replaced by isoform 2.|||Homodimer; the filamin repeat 24 and the second hinge domain are important for dimer formation (By similarity). Interacts with FLNB, INPPL1, ITGB1A, KCND2, MYOT, MYOZ1 and MYOZ3. Interacts with sarcoglycans SGCD and SGCG. Interacts (via filament repeats 17-18, 20-21 and 24) with USP25 (isoform USP25m only). Interacts with FBLIM1 (By similarity). Interacts with XIRP1; this interaction is mediated by filamin 20 repeat (By similarity). Interacts with KY. Interacts with IGFN1. Interacts with MICALL2. Interacts with ANK3. Interacts with MICALL2 (By similarity). Interacts with ANK3. Interacts with SYNPO2 (By similarity).|||Membrane|||Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (By similarity). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (PubMed:16914736).|||Ubiquitinated by FBXL22, leading to proteasomal degradation.|||Z line|||cytoskeleton http://togogenome.org/gene/10090:Trappc2l ^@ http://purl.uniprot.org/uniprot/Q9JME7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAPP small subunits family. Sedlin subfamily.|||Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12. Interacts with the heterodimer TRAPPC3-TRAPPC6A (By similarity).|||Endoplasmic reticulum|||Golgi apparatus|||May play a role in vesicular transport from endoplasmic reticulum to Golgi.|||perinuclear region http://togogenome.org/gene/10090:Gm45935 ^@ http://purl.uniprot.org/uniprot/B4XVP7 ^@ Subcellular Location Annotation ^@ Chromosome http://togogenome.org/gene/10090:Krt36 ^@ http://purl.uniprot.org/uniprot/B1AQ75 ^@ Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||In skin, only expressed in the suprabasal cells of tail scale epidermis. Suprabasally expressed in stratified squamous epithelia and also in the posterior unit of the complex filiform papillae of tongue. Expressed in rare anatomical sites in which an orthokeratinized stratum corneum would be too soft and a hard keratinized structure would be too rigid to meet the functional requirement of the respective epithelia.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).|||mRNA synthesis is suppressed during retinoic acid-mediated orthokeratotic conversion of tail scale epidermis. http://togogenome.org/gene/10090:Lamp1 ^@ http://purl.uniprot.org/uniprot/P11438|||http://purl.uniprot.org/uniprot/Q3TA96|||http://purl.uniprot.org/uniprot/Q3TX84|||http://purl.uniprot.org/uniprot/Q9DC13 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LAMP family.|||Cell membrane|||Cytolytic granule membrane|||Deficient mice are viable and fertile (PubMed:10212251). However, mice deficient in both Lamp1 and Lamp2 are embryonic lethal, with the accumulation of autophagic vacuoles in many tissues (PubMed:15121881). In addition, LAMP1 deletion results in increased NK-cell apoptosis upon target cell-induced degranulation (PubMed:23847195).|||Endosome membrane|||Interacts with ABCB9; this interaction strongly stabilizes ABCB9 and protects ABCB9 against lysosomal degradation (PubMed:22641697). Interacts with FURIN (By similarity). Interacts with TMEM175; inhibiting the proton channel activity of TMEM175 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Late endosome membrane|||Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation, autophagy and cholesterol homeostasis (PubMed:15121881). Acts as an important regulator of lysosomal lumen pH regulation by acting as a direct inhibitor of the proton channel TMEM175, facilitating lysosomal acidification for optimal hydrolase activity (By similarity). Also plays an important role in NK-cells cytotoxicity (PubMed:23847195). Mechanistically, participates in cytotoxic granule movement to the cell surface and perforin trafficking to the lytic granule (By similarity). In addition, protects NK-cells from degranulation-associated damage induced by their own cytotoxic granule content (PubMed:23847195). Presents carbohydrate ligands to selectins (By similarity). Also implicated in tumor cell metastasis (PubMed:2676155).|||Lysosome membrane|||Membrane|||O- and N-glycosylated; some of the N-glycans attached to LAMP-1 are polylactosaminoglycans. http://togogenome.org/gene/10090:Per1 ^@ http://purl.uniprot.org/uniprot/O35973 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals show disrupted circadian behavior. The prolongation of light exposure produces larger phase delay of behavioral rhythm compared to wild-types. Double knocknouts for PER2 and PER1 show an abrupt loss of rhythmicity immediately upon transfer to exprosure to constant darkness. Animals have largely affected the water intake (polydipsia) and urine volume (polyuria).|||Cytoplasm|||Expressed in the suprachiasmatic nucleus (SCN) during late fetal and early neonatal life.|||Homodimer (PubMed:22331899). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:11779462). Interacts directly with TIMELESS (PubMed:10231394, PubMed:9856465). Interacts directly with PER2, PER3, CRY1 and CRY2 (PubMed:10428031, PubMed:10848614, PubMed:11875063, PubMed:14701732, PubMed:16478995, PubMed:24154698). Interacts with BMAL1 and CLOCK (PubMed:16717091, PubMed:24154698). Interacts with GPRASP1 (By similarity). Interacts (phosphorylated) with BTRC and FBXW11; the interactions trigger proteasomal degradation (By similarity). Interacts with NONO and SFPQ (PubMed:22966205). Interacts with WDR5 (By similarity). Interacts with U2AF1L4 (Isoform 3) (PubMed:24837677). Interacts with USP2 (PubMed:23213472). Interacts with HNF4A (By similarity).|||In brain, highest expression is observed in the SCN. Highly expressed in the pyramidal cell layer of the piriform cortex, the periventricular part of the caudate-putamen, many thalamic nuclei, and the granular layer of the cerebellar cortex. Weaker expression is detected in most area of the brain, including cortical and non cortical structures. Expression but no oscillations occurs in the glomerular and mitral cell layers of the olfactory bulb, the internal granular layer of the cerebellum, the cornu ammonis and dentate gyrus of the hippocampus, the cerebral and piriform cortices. Expressed in the renal cortex (at protein level). Also found in heart, brain, bladder, lumbar spinal cord, spleen, lung, liver, skeletal muscle and testis.|||In the suprachiasmatic nucleus (SCN), behaves like a day-type oscillator, with maximum expression during the light period. Oscillations are maintained under constant darkness and are responsive to changes of the light/dark cycles. There is a 4 hour time delay between PER1 and PER2 oscillations. The expression rhythms appear to originate from retina. In liver, peak levels at CT9. In the SCN, levels increase by light exposure during subjective night. Circadian oscillations also observed in skeletal muscle, bladder, lumbar spinal cord and liver but not in testis.|||Nucleus|||Phosphorylated on serine residues by CSNK1D, CSNK1E and probably also by CSNK1G2. Phosphorylation by CSNK1D or CSNK1E promotes nuclear location of PER proteins as well as ubiquitination and subsequent degradation. May be dephosphorylated by PP1.|||Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by BMAL1:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1.|||Ubiquitinated; requires phosphorylation by CSNK1E and interaction with BTRC and FBXW11. Deubiquitinated by USP2. http://togogenome.org/gene/10090:Cdc45 ^@ http://purl.uniprot.org/uniprot/F8WJ72|||http://purl.uniprot.org/uniprot/Q3UI99|||http://purl.uniprot.org/uniprot/Q9Z1X9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated with ORC2. Interacts with HELB (By similarity). Component of the CMG helicase complex, composed of the MCM2-7 complex, the GINS complex and CDC45 (By similarity).|||Belongs to the CDC45 family.|||Nucleus|||Required for initiation of chromosomal DNA replication.|||Widely expressed. http://togogenome.org/gene/10090:Golm2 ^@ http://purl.uniprot.org/uniprot/E9PZJ6|||http://purl.uniprot.org/uniprot/Q6P2L7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the GOLM family.|||Membrane http://togogenome.org/gene/10090:Nacad ^@ http://purl.uniprot.org/uniprot/Q5SWP3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NAC-alpha family.|||Cytoplasm|||May prevent inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). May bind to nascent polypeptide chains as they emerge from the ribosome and block their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. May also reduce the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Bicdl2 ^@ http://purl.uniprot.org/uniprot/Q8CHW5 ^@ Similarity|||Subunit ^@ Belongs to the BICDR family.|||Interacts with RAB13. http://togogenome.org/gene/10090:Frk ^@ http://purl.uniprot.org/uniprot/Q922K9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cytoplasm|||Expressed in intestinal tract, fetal and adult islets of Langerhans, kidney, liver and lung.|||Interacts (via the SH3-domain) with PTEN. Interacts with RB1 (By similarity).|||Mice are viable and do not show any histological abnormalities in epithelial tissues or develop any pathological and/or metabolic disorders associated with the failure of epithelial organs.|||Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm20828 ^@ http://purl.uniprot.org/uniprot/J3KMI7 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Map1lc3b ^@ http://purl.uniprot.org/uniprot/Q9CQV6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3 different light chains, LC1, LC2 and LC3, can associate with MAP1A and MAP1B proteins (By similarity). Interacts at microtubules with CABP1 (via EF-hands 1 and 2) but not with calmodulin. Interacts with FYCO1 (via C-terminus). Interacts with TP53INP1 and TP53INP2 (By similarity). Interacts with TBC1D25 (PubMed:21383079). Directly interacts with SQSTM1; this interaction leads to MAP1LC3B recruitment to inclusion bodies containing polyubiquitinated protein aggregates and to inclusion body degradation by autophagy. Interacts with ATG4B, MAPK15 and BNIP3. Interacts with MAPB1, KEAP1, PCM1, OFD1, CEP131, and TECPR2. Interacts with TBC1D5. Found in a complex with UBQLN1 and UBQLN2. Interacts with UBQLN4 (via STI1 1 and 2 domains). Interacts with UBQLN1 in the presence of UBQLN4. Interacts with ATG13. Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3 (PubMed:34338405). Interacts with PLCL1; the interaction inhibits autophagosome formation (PubMed:23399561). Interacts with TRIM16. Interacts with CRY1 and PER2 (PubMed:29937374). Interacts with the reticulophagy receptor TEX264 (By similarity). Membrane-bound form LC3-II interacts with PHB1 and PHB2; the interaction takes place upon Parkin-mediated mitochondrial damage (By similarity). Interacts with PJVK; the interaction is direct (PubMed:30936319). Interacts with KBTBD6 and KBTBD7; the interaction is direct (By similarity). Interacts with AMBRA1 (via LIR motif) (By similarity). Interacts with JMY; the interaction results in the activation of JYM's nucleation activity in the cytoplasm (By similarity). Interacts with MOAP1 (via LIR motif) (By similarity). Interacts with TAX1BP1 (By similarity). Interacts with Irgm1 (By similarity). Interacts with STX17 (By similarity).|||Belongs to the ATG8 family.|||Cytoplasmic vesicle|||Endomembrane system|||Mitochondrion membrane|||Phosphorylation by PKA inhibits conjugation of phosphatidylethanolamine (PE). Interaction with MAPK15 reduces the inhibitory phosphorylation and increases autophagy activity.|||The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, LC3-I (PubMed:12207896, PubMed:14530254). The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, LC3-II (By similarity). During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid (By similarity). ATG4 proteins also mediate the delipidation of PE-conjugated forms (PubMed:33795848). In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy (By similarity). ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (PubMed:33795848).|||Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. In response to cellular stress and upon mitochondria fission, binds C-18 ceramides and anchors autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. Upon nutrient stress, directly recruits cofactor JMY to the phagophore membrane surfaces and promotes JMY's actin nucleation activity and autophagosome biogenesis during autophagy.|||autophagosome membrane|||cytoskeleton http://togogenome.org/gene/10090:Hnrnpu ^@ http://purl.uniprot.org/uniprot/Q8VEK3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Arg-709 and Arg-715 are dimethylated, probably to asymmetric dimethylarginine.|||Cell surface|||Chromosome|||Citrullinated by PADI4.|||Cleaved at Asp-94 by CASP3 during T-cell apoptosis, resulting in a loss of DNA- and chromatin-binding activities.|||Cytoplasm|||Cytoplasmic granule|||DNA- and RNA-binding protein involved in several cellular processes such as nuclear chromatin organization, telomere-length regulation, transcription, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing and mitotic cell progression (PubMed:20833368, PubMed:21235343, PubMed:22162999, PubMed:26244333). Plays a role in the regulation of interphase large-scale gene-rich chromatin organization through chromatin-associated RNAs (caRNAs) in a transcription-dependent manner, and thereby maintains genomic stability (By similarity). Required for the localization of the long non-coding Xist RNA on the inactive chromosome X (Xi) and the subsequent initiation and maintenance of X-linked transcriptional gene silencing during X-inactivation (PubMed:20833368, PubMed:26244333). Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator (PubMed:21235343, PubMed:22162999). Promotes transcription initiation by direct association with the core-TFIIH basal transcription factor complex for the assembly of a functional pre-initiation complex with Pol II in a actin-dependent manner. Blocks Pol II transcription elongation activity by inhibiting the C-terminal domain (CTD) phosphorylation of Pol II and dissociates from Pol II pre-initiation complex prior to productive transcription elongation. Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus. Negatively regulates glucocorticoid-mediated transcriptional activation (By similarity). Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling (PubMed:21235343). Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression (By similarity). Participates in the circadian regulation of the core clock component BMAL1 transcription (PubMed:18332112). Plays a role in the regulation of telomere length. Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis. Plays a role in mRNA stability. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Enhances the expression of specific genes, such as tumor necrosis factor TNFA, by regulating mRNA stability, possibly through binding to the 3'-untranslated region (UTR). Plays a role in mitotic cell cycle regulation. Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression. Phosphorylation at Ser-58 by PLK1 is required for chromosome alignement and segregation and progression through mitosis. Contributes also to the targeting of AURKA to mitotic spindle MTs. Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides. Binds to chromatin-associated RNAs (caRNAs). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner (By similarity). Binds (via RNA-binding RGG-box region) to the long non-coding Xist RNA; this binding is direct and bridges the Xist RNA and the inactive chromosome X (Xi) (PubMed:20833368, PubMed:26244333). Binds the long non-coding H19 RNA. Binds to SMN1/2 pre-mRNAs at G/U-rich regions. Binds to small nuclear RNAs (snRNAs). Binds to the 3'-UTR of TNFA mRNA (By similarity). Also negatively regulates embryonic stem cell differentiation upon LIF signaling (PubMed:21235343). Required for embryonic development (PubMed:16022389). Binds to brown fat long non-coding RNA 1 (Blnc1); facilitates the recruitment of Blnc1 by ZBTB7B required to drive brown and beige fat development and thermogenesis (PubMed:28784777).|||Extensively phosphorylated. Phosphorylated on Ser-58 by PLK1 and dephosphorylated by protein phosphatase 2A (PP2A) in mitosis.|||Mice exhibit early embryonic lethality between 9.5 and 11.5 dpc (PubMed:16022389). Mice show retarded development of embryonic ectoderm at 6.5 dpc and growth retardation beginning at 7.5 dpc (PubMed:16022389).|||Midbody|||Nucleus|||Nucleus matrix|||Nucleus speckle|||Oligomer (via ATPase domain and RNA-binding RGG-box region); oligomerization occurs upon ATP-binding in a chromatin-associated RNAs (caRNAs)- and transcription-dependent manner and is required for chromatin decompaction. ATP hydrolysis is required to cycle from an oligomeric to monomeric state to compact chromatin. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Associates with heterogeneous nuclear ribonucleoprotein (hnRNP) particles (By similarity). Associates (via middle region) with the C-terminal domain (CTD) RNA polymerase II (Pol II) holoenzyme; this association occurs in a RNA-independent manner (PubMed:21235343). Associates (via middle region) with the core-TFIIH basal transcription factor complex; this association inhibits the CTD phosphorylation of RNA polymerase II holoenzyme by down-regulating TFIIH kinase activity. Associates with the telomerase holoenzyme complex. Associates with spindle microtubules (MTs) in a TPX2-dependent manner. Interacts (via C-terminus) with actin; this interaction is direct and mediates association with the phosphorylated CTD of RNA polymerase II and is disrupted in presence of the long non-coding H19 RNA. Interacts with AURKA. Interacts (via C-terminus) with CBX5; this interaction is, at least in part, RNA-dependent. Interacts with CR2 (By similarity). Interacts with CRY1 (PubMed:19129230). Interacts (via C-terminus) with EP300; this interaction enhances DNA-binding to nuclear scaffold/matrix attachment region (S/MAR) elements. Interacts with ERBB4. Interacts with GEMIN5. Interacts with IGF2BP1. Interacts with IGF2BP2 and IGF2BP3. Interacts with NCL; this interaction occurs during mitosis. Interacts (via C-terminus) with NR3C1 (via C-terminus). Interacts with PLK1; this interaction induces phosphorylation of HNRNPU at Ser-58 in mitosis. Interacts with POU3F4 (By similarity). Interacts with SMARCA4; this interaction occurs in embryonic stem cells and stimulates global Pol II-mediated transcription (PubMed:22162999). Interacts (via C-terminus) with TOP2A; this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA by TOP2A in a RNA-dependent manner. Interacts with TPX2; this interaction recruits HNRNPU to spindle microtubules (MTs). Interacts with UBQLN2 (By similarity). Interacts (via RNA-binding RGG-box region) with ZBTB7B; the interaction facilitates the recruitment of long non-coding RNA Blnc1 by ZBTB7B (PubMed:28784777). Interacts with ERCC6 (By similarity).|||The SAP domain is necessary for specific binding to nuclear scaffold/matrix attachment region (S/MAR) elements in DNA. The RNA-binding RGG-box region is necessary for its association with inactive X chromosome (Xi) regions and to chromatin-associated RNAs (caRNAs) (By similarity). Both the DNA-binding domain SAP and the RNA-binding RGG-box region are necessary for the localization of Xist RNA on the Xi (PubMed:20833368). The ATPase and RNA-binding RGG-box regions are necessary for oligomerization (By similarity).|||centrosome|||kinetochore|||spindle|||spindle pole http://togogenome.org/gene/10090:Fbxl3 ^@ http://purl.uniprot.org/uniprot/Q8C4V4 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Mice show defects in behavioral rhythms with an extremely long-period activity phenotype. The onset of active phase is abnormally delayed from the light-to-dark transition: in constant darkness (DD), mice show significantly longer rhythmic activities. Mice lacking both Fbxl3 and Fbxl21 show an attenuated phenotype in behavioral rhythm compared to Fbxl3-deficient mice; however, they exhibit unstable behavioral rhythms, sometimes eliciting arrhythmicity.|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL3) composed of CUL1, SKP1, RBX1 and FBXL3. Interacts with HDAC3 (PubMed:26776516). Interacts with CRY1 and CRY2 (phosphorylated) (PubMed:23452856, PubMed:30500822). Interacts with KDM8 (PubMed:30500822).|||Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2. Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex.|||Ubiquitously expressed but enriched in brain. Diffusely expressed in the suprachiasmatic nucleus, SCN.|||Undergoes autophagy-mediated degradation in the liver in a time-dependent manner. http://togogenome.org/gene/10090:Rdh19 ^@ http://purl.uniprot.org/uniprot/G5E8H9 ^@ Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. http://togogenome.org/gene/10090:Vmn1r83 ^@ http://purl.uniprot.org/uniprot/Q8R287 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dhx34 ^@ http://purl.uniprot.org/uniprot/Q9DBV3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Forms a complex with RUVBL1 and RUVBL2 (By similarity). Part of a complex composed of SMG1, DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein to facilitate SMG1 phosphorylation of UPF1 (By similarity). Interacts with UPF1, MOV10, EIF4A3, XRN2, SMG6, SMG7, SMG9, UPF3A, UPF3B, CASC3/MLN51, XRN1, DIS3 and DCP1A; the interactions are RNA-independent (By similarity). Interacts with NCBP1/CPB80; the interaction is RNA-dependent (By similarity). Interacts (via C-terminus) with SMG1; the interaction is RNA-independent (By similarity).|||Probable ATP-binding RNA helicase (By similarity). Required for nonsense-mediated decay (NMD) degradation of mRNA transcripts containing premature stop codons (By similarity). Promotes the phosphorylation of UPF1 along with its interaction with key NMD pathway proteins UPF2 and EIF4A3 (By similarity). Negatively regulates the nucleotide binding ability and ATP hydrolysis of the RUVBL1-RUVBL2 complex via induction of N-terminus conformation changes of the RUVBL2 subunits (By similarity). http://togogenome.org/gene/10090:Mast4 ^@ http://purl.uniprot.org/uniprot/E9PWX8|||http://purl.uniprot.org/uniprot/E9QPR4|||http://purl.uniprot.org/uniprot/Q811L6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm http://togogenome.org/gene/10090:Slc46a3 ^@ http://purl.uniprot.org/uniprot/Q9DC26 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. SLC46A family.|||Expressed in liver, kidney, small intestine and colon.|||In liver, expression gradually increases up to 8 weeks of age.|||In liver, expression is induced by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); the induction is mediated by AHR.|||Knockout mice have liver copper levels increased by around 30%, with no differences in iron contents. Mutants are resistant to TCDD and high-fat diet-induced hepatic triglyceride accumlation and after 3 of high-fat diet feeding, body weight changes, liver mass and epididymal fat mass are reduced compared to wild-type mice.|||Lysosomal proton-coupled steroid conjugate and bile acid transporter. Preferentially recognizes lipophilic steroid conjugates or bile acis as endogenous substrates and seems to mediate escape from lysosomes to the cytoplasm (By similarity). Modulates hepatic cytosolic copper homeostasis, maybe acting as a lysosomal copper transporter and sequestering copper ions in the lysosome (PubMed:33436590). Delivers pathogen-associated molecular patterns to cytosolic pattern recognition receptors as part of the innate immune response to microbes. Selectively transports bacterial muramyl dipeptide (MDP) into the cytosol for recognition by NOD2, triggering inflammatory responses (PubMed:28539433, PubMed:37116499). Likely acts as a redundant importer of cyclic GMP-AMP dinucleotides (cGAMPs) in monocyte and macrophage cell lineages (PubMed:34235268). The transport mechanism, its electrogenicity and stoichiometry remain to be elucidated (Probable).|||Lysosome membrane http://togogenome.org/gene/10090:Snx12 ^@ http://purl.uniprot.org/uniprot/O70493 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||May be involved in several stages of intracellular trafficking.|||Membrane|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate. http://togogenome.org/gene/10090:Cela2a ^@ http://purl.uniprot.org/uniprot/P05208 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Elastase subfamily.|||Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism. Circulates in plasma and reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity.|||Highly expressed in pancreas (at mRNA and protein levels). Also expressed in adrenal gland and small intestine.|||Interacts with CPA1. Interacts with SERPINA1.|||Secreted http://togogenome.org/gene/10090:Wrap53 ^@ http://purl.uniprot.org/uniprot/Q8VC51 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCAB1 family.|||Cajal body|||Chromosome|||Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. Interacts with the chaperonin-containing T-complex (TRiC) complex; which mediates the folding of WRAP53/TCAB1. Interacts with COIL. Interacts with SMN1. Interacts with RNF8. Interacts with histone H2AX.|||Phosphorylated at Ser-61 by ATM in response to DNA damage, promoting its interaction with histone H2AX and localization to sites of DNA double-strand breaks.|||RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies (PubMed:29804836). Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC) (PubMed:29804836). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes (By similarity). In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex (PubMed:29804836). Acts by specifically binding the CAB box of the TERC RNA and controlling the folding of the CR4/CR5 region of the TERC RNA, a critical step for telomerase activity (By similarity). In addition, also controls telomerase holoenzyme complex localization to Cajal body (By similarity). During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity (By similarity). In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies (By similarity). Also plays a role in DNA repair: phosphorylated by ATM in response to DNA damage and relocalizes to sites of DNA double-strand breaks to promote the repair of DNA double-strand breaks (By similarity). Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non-homologous end joining (NHEJ) (By similarity).|||telomere http://togogenome.org/gene/10090:Rdh8 ^@ http://purl.uniprot.org/uniprot/D3Z6W3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Membrane|||Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinal to all-trans-retinol. May play a role in the regeneration of visual pigment at high light intensity. http://togogenome.org/gene/10090:Eef1akmt2 ^@ http://purl.uniprot.org/uniprot/Q9D853 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM4 family.|||Cytoplasm|||Nucleus|||Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-318'. http://togogenome.org/gene/10090:Tnpo3 ^@ http://purl.uniprot.org/uniprot/Q6P2B1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Importin, which transports target proteins into the nucleus. Specifically mediates the nuclear import of splicing factor serine/arginine (SR) proteins, such as RBM4, SFRS1 and SFRS2, by recognizing phosphorylated SR domains. Also mediates the nuclear import of serine/arginine (SR) protein CPSF6, independently of CPSF6 phosphorylation. The nuclear import process is regulated by the small GTPase Ran that partitions between cytoplasm and nucleus in the predominantly GDP- and GTP-bound form, respectively. Importin associates with target cargo proteins in the cytoplasm, and the competitive binding of GTP-bound Ran induces the release of cargos in the nucleus.|||Interacts with (GTP-bound) Ran. Interacts with (phosphorylated) SFRS1 and SFRS2; leading to their nuclear import. Interacts with NUP62. Interacts with RBM4. Interacts with CPSF6, promoting its nuclear import.|||Nucleus envelope http://togogenome.org/gene/10090:Cyp2b19 ^@ http://purl.uniprot.org/uniprot/O55071 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Expressed only in differentiated keratinocytes in skin.|||Microsome membrane http://togogenome.org/gene/10090:Dpyd ^@ http://purl.uniprot.org/uniprot/Q8CHR6 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dihydropyrimidine dehydrogenase family.|||Binds 2 FAD.|||Binds 2 FMN.|||Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms per subunit.|||Cytoplasm|||Homodimer.|||Inactivated by 5-iodouracil.|||Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil. http://togogenome.org/gene/10090:Dppa2 ^@ http://purl.uniprot.org/uniprot/B2RQ54|||http://purl.uniprot.org/uniprot/Q9CWH0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to target gene promoters, including NKX2-5 and SYCE1, but not GATA4, and may be involved in the maintenance of the active epigenetic status of these genes.|||Expressed in 4-cell embryo, morula and blastocyst. At 7.5 dpc, detected in the epiblast. At 10.0 dpc, expressed in the primordial germ cells. Expression decreases at 12.0 dpc in the embryonic gonads. At 14.5 dpc, expression is restricted to testis. 6 days after birth, still detected in primitive type A spermatogonia. Expressed in undifferentiated embryonic stem cells, but expression rapidly decreases upon differentiation.|||Interacts with DPPA4.|||Mutant animals show survival rates similar to wild-type until 16.5 dpc. Then mortality increases and no animals survive beyond weaning age. At 18.5 dpc, the lungs of mutants mice show a thicker mesenchyme and smaller alveolar space than those of wild-type animals.|||Not detected in adult tissues.|||Nucleus http://togogenome.org/gene/10090:Amigo1 ^@ http://purl.uniprot.org/uniprot/Q80ZD8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. AMIGO family.|||Cell membrane|||Expressed in hippocampal and cortical neurons (at protein level) (PubMed:22056818). High levels in cerebellum, cerebrum, and retina. Low levels in liver, kidney, small intestine, spleen, lung and heart.|||Homodimer, and heterodimer with AMIGO2 and AMIGO3 (PubMed:21983541). Interacts with KCNB1 (PubMed:22056818).|||Perikaryon|||Promotes growth and fasciculation of neurites from cultured hippocampal neurons. May be involved in fasciculation as well as myelination of developing neural axons. May have a role in regeneration as well as neural plasticity in the adult nervous system. May mediate homophilic as well as heterophilic cell-cell interaction and contribute to signal transduction through its intracellular domain (By similarity). Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:22056818).|||The LRR repeat region mediates homodimerization.|||dendrite http://togogenome.org/gene/10090:Gm21127 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Prkar1a ^@ http://purl.uniprot.org/uniprot/Q9DBC7 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cAMP-dependent kinase regulatory chain family.|||Cell membrane|||Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.|||The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. Interacts with PRKACA and PRKACB (By similarity). PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4 (PubMed:9852104). Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with PRKX; regulates this cAMP-dependent protein kinase (By similarity). Interacts with CBFA2T3 (PubMed:20138877). Interacts with smAKAP; this interaction may target PRKAR1A to the plasma membrane. Interacts with AICDA (By similarity).|||The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.|||Two types of regulatory chains are found: type I, which predominates in skeletal muscle, and type II, which predominates in cardiac muscle. http://togogenome.org/gene/10090:Tbx6 ^@ http://purl.uniprot.org/uniprot/P70327 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Defects in the differentiation of paraxial mesoderm. Irregular somites formed in the neck region of mutant embryos, whereas more posterior paraxial tissue did not form somites but instead differentiated along a neural pathway, forming neural-tube-like structures that flanked the axial neural tube. These paraxial tubes showed dorsal/ventral patterning that is characteristic of the neural tube and had differentiated motor neurons. Embryos lacking TBX6 show also randomization of the direction of heart looping and independent alterations in the direction of embryo turning.|||Nucleus|||T-box transcription factor that plays an essential role in the determination of the fate of axial stem cells: neural vs mesodermal. Acts in part by down-regulating, a specific enhancer (N1) of SOX2, to inhibit neural development. Seems to play also an essential role in left/right axis determination and acts through effects on Notch signaling around the node as well as through an effect on the morphology and motility of the nodal cilia.|||TBX6 is first detected in the gastrulation stage in the primitive streak and newly recruited paraxial mesoderm. Later in development it is restricted to presomitic, paraxial mesoderm and to the tail bud, which replaces the streak as the source of mesoderm. http://togogenome.org/gene/10090:Aagab ^@ http://purl.uniprot.org/uniprot/Q8R2R3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associated with AP-1 and AP-2 complexes.|||May be involved in endocytic recycling of growth factor receptors such as EGFR.|||cytosol http://togogenome.org/gene/10090:Lmnb2 ^@ http://purl.uniprot.org/uniprot/P21619|||http://purl.uniprot.org/uniprot/Q3V159 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ B-type lamins undergo a series of modifications, such as farnesylation and phosphorylation. Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations.|||Belongs to the intermediate filament family.|||Interacts with TMEM43.|||Isoform B3 is germ cell specific.|||Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin.|||Nucleus lamina|||The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively. http://togogenome.org/gene/10090:Haus7 ^@ http://purl.uniprot.org/uniprot/Q8BKT8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS7 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (By similarity). Interacts with UCHL5 (PubMed:11163772). Interacts with EML3 (phosphorylated at 'Thr-882') (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||centrosome|||spindle http://togogenome.org/gene/10090:Cks1b ^@ http://purl.uniprot.org/uniprot/P61025 ^@ Function|||Similarity|||Subunit ^@ Belongs to the CKS family.|||Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.|||Forms a homohexamer that can probably bind six kinase subunits. http://togogenome.org/gene/10090:B4galt1 ^@ http://purl.uniprot.org/uniprot/P15535|||http://purl.uniprot.org/uniprot/Q3U478 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 7 family.|||Cell membrane|||Cell surface|||Golgi apparatus membrane|||Golgi stack membrane|||Homodimer; and heterodimer with alpha-lactalbumin to form lactose synthase (By similarity). Interacts (via N-terminal cytoplasmic domain) with UBE2Q1 (via N-terminus); the interaction is direct (PubMed:18511602).|||In the brain, highest levels of expression are found at 11.5 dpc with decreased expression thereafter.|||Membrane|||Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.|||Secreted|||The Golgi complex form catalyzes the production of lactose in the lactating mammary gland and could also be responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.|||The cell surface form functions as a recognition molecule during a variety of cell to cell and cell to matrix interactions, as those occurring during development and egg fertilization, by binding to specific oligosaccharide ligands on opposing cells or in the extracellular matrix. The secreted form is responsible for the synthesis of complex-type to N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.|||The soluble form derives from the membrane forms by proteolytic processing.|||filopodium http://togogenome.org/gene/10090:Iars2 ^@ http://purl.uniprot.org/uniprot/E9PWN3|||http://purl.uniprot.org/uniprot/Q8BIJ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Mitochondrion matrix http://togogenome.org/gene/10090:Unc80 ^@ http://purl.uniprot.org/uniprot/Q8BLN6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary subunit of the NALCN sodium channel complex (PubMed:32620897, PubMed:19092807, PubMed:21040849). The NALCN sodium channel complex is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability (PubMed:32620897). This complex is activated by neuropeptides substance P, neurotensin. In addition, the channel is inhibited by extracellular Ca(2+) through the Ca(2+)-sensing receptor. UNC80 is essential for NALCN sensitivity to extracellular calcium.|||Belongs to the unc-80 family.|||Cell membrane|||Expressed almost exclusively in the brain (PubMed:26708753). Expressed in hippocampus and ventral tegmental area neurons (PubMed:19092807).|||Knockout leads to severe apnea and neonatal lethality. No mice pups survive beyond 24 hours of birth. Hippocampal neurons show decreased NALCN-dependent sodium leak current.|||NALCN complex consists of NALCN and auxiliary subunits, UNC79, UNC80 and NACL1 (PubMed:32620897, PubMed:19092807, PubMed:21040849, PubMed:26708751). These auxiliary subunits are essential for the NALCN complex function (PubMed:32620897). Interacts (via N-terminus half) with NALCN; this interaction facilitates NALCN surface localization (PubMed:19092807, PubMed:21040849, PubMed:32620897). Interacts (via C-terminus) with UNC79 (PubMed:19092807, PubMed:21040849, PubMed:32620897, PubMed:26708751). UNC80 bridges NALCN to UNC79 (PubMed:21040849, PubMed:32620897).|||Phosphorylated on tyrosine residues.|||dendrite http://togogenome.org/gene/10090:Syngr3 ^@ http://purl.uniprot.org/uniprot/Q8R191 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptogyrin family.|||Expression increases during brain development from P2 to adult (at protein level).|||Interacts (via N-terminus) with SLC6A3 (via N-terminus) (PubMed:19357284). May interact with VMAT2 (PubMed:19357284).|||May play a role in regulated exocytosis (PubMed:10383386). May indirectly regulate the activity of the plasma membrane dopamine transporter SLC6A3 and thereby regulate dopamine transport back from the synaptic cleft into the presynaptic terminal (PubMed:19357284).|||Specifically expressed in brain. Found in the brain across the dorsal and ventral corpus striatum as well as in the cortex.|||Synapse|||synaptic vesicle membrane http://togogenome.org/gene/10090:Stk33 ^@ http://purl.uniprot.org/uniprot/Q924X7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Highly expressed in testis, particularly in cells from the spermatogenic epithelia. Significant expression is detected in lung epithelia, alveolar macrophages, horizontal cells in the retina and in embryonic organs such as heart, brain and spinal cord. Also expressed in pituitary gland, kidney, pancreas, trachea and thyroid gland.|||Interacts with VIME.|||Serine/threonine protein kinase which phosphorylates VIME. May play a specific role in the dynamic behavior of the intermediate filament cytoskeleton by phosphorylation of VIME.|||perinuclear region http://togogenome.org/gene/10090:Hyal3 ^@ http://purl.uniprot.org/uniprot/Q8VEI3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 56 family.|||Cell membrane|||Early endosome|||Endoplasmic reticulum|||Expressed in testis, epididymal tissue, epididymal luminal fluid (ELF), acrosome-intact (AI) sperm and caput (CAP), corpus (COR) and caudal (CAU) sperm. Higher expression in sperm than testis (at protein level) (PubMed:20586096). Liver, kidney, skin, brain, stomach and testis (PubMed:11929860). Expressed mainly in granulosa cells of the ovaries. Expressed in small and large antral follicles. Not present in theca or stroma cells (PubMed:18653706). Expressed in testis and liver (PubMed:18762256). Expressed in testis and CAP, COR, and CAU epididymis tissue (PubMed:20586096).|||Facilitates sperm penetration into the layer of cumulus cells surrounding the egg by digesting hyaluronic acid. Involved in induction of the acrosome reaction in the sperm (PubMed:20586096). Involved in follicular atresia, the breakdown of immature ovarian follicles that are not selected to ovulate. Induces ovarian granulosa cell apoptosis, possibly via apoptotic signaling pathway involving CASP8 and CASP3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage (PubMed:18653706). Has no hyaluronidase activity in embryonic fibroblasts in vitro (PubMed:18234732). Has no hyaluronidase activity in granulosa cells in vitro (PubMed:18653706).|||N-glycosylated.|||No visible phenotype. Both male and female mice are viable. Skeletal features, joints, whole-body weights, organ weights, organ morphologies and the serum hyaluronic acid (HA) levels are normal. No evidence of glycosaminoglycan accumulation, including vacuolization, in tissues analyzed including liver, lung, kidney, spleen, skin, fat, testes and seminal vesicles at 12-14 months of age. No difference in tissue organization or connective tissue thickness. Only a subtle change in the alveolar structure and extracellular matrix thickness in lung tissue sections at 12-14 months of age. Lungs have larger alveoli and more areas of thickened interstitium. Lung tissues from 6 months old mice show more immature alveoli compared to wild-type (PubMed:18762256). Mice are fully fertile (PubMed:18762256, PubMed:20586096). Sperm show delayed cumulus penetration and reduced acrosomal exocytosis (PubMed:20586096).|||Secreted|||Up-regulated expression in apoptotic granulosa cells and in atretic follicles of the ovaries (PubMed:18653706).|||acrosome http://togogenome.org/gene/10090:Vmn1r66 ^@ http://purl.uniprot.org/uniprot/Q8K4I0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Scgb1b20 ^@ http://purl.uniprot.org/uniprot/E9PWZ2 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Vmn1r67 ^@ http://purl.uniprot.org/uniprot/A6H640|||http://purl.uniprot.org/uniprot/G5E8C1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Uts2 ^@ http://purl.uniprot.org/uniprot/Q541G7|||http://purl.uniprot.org/uniprot/Q9QZQ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the urotensin-2 family.|||Brain specific. Predominantly expressed in motoneurons of the brainstem and spinal cord.|||Highly potent vasoconstrictor.|||Secreted http://togogenome.org/gene/10090:Metap2 ^@ http://purl.uniprot.org/uniprot/O08663|||http://purl.uniprot.org/uniprot/Q58E65 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.|||Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.|||Binds EIF2S1 at low magnesium concentrations. Interacts strongly with the eIF-2 gamma-subunit EIF2S3.|||Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.|||Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).|||Cytoplasm|||Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis. http://togogenome.org/gene/10090:Tut1 ^@ http://purl.uniprot.org/uniprot/Q8R3F9 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adenylyltransferase activity is specifically phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).|||Associates with the cleavage and polyadenylation specificity factor (CPSF) complex. Interacts with CPSF1 and CPSF3; the interaction is direct. Interacts with PIP5K1A.|||Belongs to the DNA polymerase type-B-like family.|||Binds 1 divalent cation per subunit.|||Nucleus speckle|||Phosphorylated by CK1 in the proline-rich (Pro-rich) region.|||Poly(A) polymerase that creates the 3'-poly(A) tail of specific pre-mRNAs. Localizes to nuclear speckles together with PIP5K1A and mediates polyadenylation of a select set of mRNAs, such as HMOX1. In addition to polyadenylation, it is also required for the 3'-end cleavage of pre-mRNAs: binds to the 3'UTR of targeted pre-mRNAs and promotes the recruitment and assembly of the CPSF complex on the 3'UTR of pre-mRNAs. In addition to adenylyltransferase activity, also has uridylyltransferase activity. However, the ATP ratio is higher than UTP in cells, suggesting that it functions primarily as a poly(A) polymerase. Acts as a specific terminal uridylyltransferase for U6 snRNA in vitro: responsible for a controlled elongation reaction that results in the restoration of the four 3'-terminal UMP-residues found in newly transcribed U6 snRNA. Not involved in replication-dependent histone mRNA degradation.|||The RRM domain is required for terminal uridylyltransferase activity. Together with the zinc-finger domain, binds the 5'-area of U6 snRNA.|||The proline-rich region is dispensable for terminal uridylyltransferase activity.|||The zinc-finger domain is required for terminal uridylyltransferase activity. Together with the RRM domain, binds the 5'-area of U6 snRNA.|||nucleolus http://togogenome.org/gene/10090:Kif20a ^@ http://purl.uniprot.org/uniprot/P97329 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Golgi apparatus|||Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle (By similarity). Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility.|||Phosphorylated by PLK1 at Ser-527 during mitosis, creating a docking site for PLK1 and recruiting PLK1 at central spindle.|||Ubiquitously expressed, with highest levels in spleen and testis.|||spindle http://togogenome.org/gene/10090:Galnt5 ^@ http://purl.uniprot.org/uniprot/Q14B51|||http://purl.uniprot.org/uniprot/Q8C102 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward EA2 peptide substrate, but has a weak activity toward Muc2 or Muc1b substrates (By similarity).|||Expressed at low level. Not expressed before E7.5 during embryogenesis. Expressed in dental mesenchyme and tongue. Accumulates in a subset of mesenchymal cells at the ventral-most portions of the 12.5 dpc maxilla and mandible underlying the dental lamina.|||Golgi apparatus membrane|||Interacts with EXT2. Does not interact with EXT1, EXTL1 or EXTL3 (By similarity).|||Membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Vmn1r45 ^@ http://purl.uniprot.org/uniprot/Q8VIC7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in a subset of sensory neurons located in the apical layer of the vomeronasal organ.|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Aspscr1 ^@ http://purl.uniprot.org/uniprot/Q8VBT9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endomembrane system|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Enhances VCP methylation catalyzed by VCPKMT (By similarity). Tethering protein that sequesters GLUT4-containing vesicles in the cytoplasm in the absence of insulin. Modulates the amount of GLUT4 that is available at the cell surface.|||Interacts with VCP. Interacts with VCPKMT (By similarity). Interacts with GLUT4.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Myh13 ^@ http://purl.uniprot.org/uniprot/B1AR69 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Utp14b ^@ http://purl.uniprot.org/uniprot/E9Q9S3|||http://purl.uniprot.org/uniprot/Q6EJB6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apparently encoded by an autosomal retrotransposed copy of the X-linked gene Utp14a. Evolution of autosomal retrogenes from X-linked progenitors compensates for X-chromosome silencing during male meiosis.|||Belongs to the UTP14 family.|||Essential for spermatogenesis. May be required specifically for ribosome biogenesis and hence protein synthesis during male meiosis.|||Expressed predominantly in germ cells of the testis; weakly expressed in brain.|||nucleolus http://togogenome.org/gene/10090:Phykpl ^@ http://purl.uniprot.org/uniprot/Q8R1K4 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the pyridoxal-phosphate-dependent breakdown of 5-phosphohydroxy-L-lysine, converting it to ammonia, inorganic phosphate and 2-aminoadipate semialdehyde.|||Does not seem to possess aminotransferase activity.|||Homotetramer.|||Mitochondrion http://togogenome.org/gene/10090:Prcd ^@ http://purl.uniprot.org/uniprot/Q00LT2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRCD family.|||Endoplasmic reticulum|||Expressed in retina, where it localizes to both rod and cone photoreceptors (at protein level).|||Golgi apparatus|||Interacts with RHO/rhodopsin; the interaction promotes PRCD stability.|||Involved in vision.|||Membrane|||Palmitoylated at Cys-2 (PubMed:27509380). Palmitoylation is essential for protein stability and trafficking to the photoreceptor outer segment, but does not appear to be essential for membrane localization (PubMed:27509380). Probably palmitoylated by ZDHHC3 (By similarity).|||Phosphorylated.|||photoreceptor outer segment http://togogenome.org/gene/10090:Cry2 ^@ http://purl.uniprot.org/uniprot/Q9R194 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals show longer circadian periods. Double knockouts of CRY1 and CRY2 show slightly decrease body weight and lose the cycling rhythmicity of feeding behavior, energy expenditure and glucocorticorids expression. Glucose homeostasis is severely disrupted and animals exhibit elevated blood glucose in response to acute feeding after an overnight fast as well as severely impaired glucose clearance in a glucose tolerance test. When challenged with high-fat diet, animals rapidly gain weight and surpass that of wild-type mice, despite displaying hypophagia. They exhibit hyperinsulinemia and selective insulin resistance in the liver and muscle but show high insulin sensitivity in adipose tissue and consequent increased lipid uptake. Mice display enlarged gonadal, subcutaneous and perirenal fat deposits with adipocyte hypertrophy and increased lipied accumulation in liver. Mice show attentuated circadian rhythms in photopic ERG b-wave amplitudes (PubMed:29561690). Both single CRY1 knockout and double CRY1 and CRY2 knockout mice show increased exercise performance and increased mitochondrial reserve capacity in primary myotubes (PubMed:28683290).|||Belongs to the DNA photolyase class-1 family.|||Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per subunit.|||Binds 1 FAD per subunit. Only a minority of the protein molecules contain bound FAD. Contrary to the situation in photolyases, the FAD is bound in a shallow, surface-exposed pocket.|||Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:11779462). Interacts with TIMELESS (PubMed:10428031). Interacts directly with PER1, PER2 and PER3; interaction with PER2 inhibits its ubiquitination and vice versa (PubMed:10428031, PubMed:11875063, PubMed:14701732, PubMed:20840750, PubMed:24154698). Interacts with CLOCK-BMAL1 (PubMed:16628007). Interacts with BMAL1 (PubMed:16717091, PubMed:19917250, PubMed:20840750). Interacts with CLOCK (PubMed:16717091, PubMed:19917250). Interacts with NFIL3 (PubMed:17274955). Interacts with FBXL3 and FBXL21 (PubMed:17462724, PubMed:23452855, PubMed:23452856). FBXL3, PER2 and the cofactor FAD compete for overlapping binding sites (PubMed:24080726, PubMed:23503662). FBXL3 cannot bind CRY2 that interacts already with PER2 or that contains bound FAD (PubMed:23503662). Interacts with PPP5C (via TPR repeats); the interaction down-regulates the PPP5C phosphatase activity on CSNK1E (By similarity). Interacts with nuclear receptors AR and NR3C1/GR; the interaction is ligand dependent (PubMed:22170608, PubMed:28751364). Interacts with PRKDC (PubMed:24158435). Interacts with CIART (PubMed:24736997). Interacts with DDB1, USP7 and TARDBP (PubMed:27123980). Interacts with HNF4A (PubMed:28751364). Interacts with PPARA (PubMed:28683290). Interacts with PPARG in a ligand-dependent manner (PubMed:28683290). Interacts with PPARD (via domain NR LBD) in a ligand-dependent manner (PubMed:28683290, PubMed:28751364). Interacts with NR1I2 (via domain NR LBD) in a ligand-dependent manner (PubMed:28751364). Interacts with NR1I3 and VDR in a ligand-dependent manner (PubMed:28751364).|||Cytoplasm|||Expression in the retina is restricted to the photoreceptor layer (at protein level) (PubMed:29561690). Expressed in all tissues examined including heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Weak expression in spleen.|||KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1 resulting in lengthening of the circadian periods. KL001-mediated CRY1 stabilization can inhibit glucagon-induced gluconeogenesis in primary hepatocytes.|||Nucleus|||Phosphorylation on Ser-265 by MAPK is important for the inhibition of CLOCK-BMAL1-mediated transcriptional activity. Phosphorylation by CSKNE requires interaction with PER1 or PER2. Phosphorylated in a circadian manner at Ser-553 and Ser-557 in the suprachiasmatic nucleus (SCN) and liver. Phosphorylation at Ser-557 by DYRK1A promotes subsequent phosphorylation at Ser-553 by GSK3-beta: the two-step phosphorylation at the neighboring Ser residues leads to its proteasomal degradation.|||Shows no clear circadian oscillation pattern in testis, cerebellum nor liver. In skeletal muscle, under constant darkness and 12 hours light:12 hours dark conditions, levels peak between ZT6 and ZT9.|||Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. May mediate circadian regulation of cAMP signaling and gluconeogenesis by blocking glucagon-mediated increases in intracellular cAMP concentrations and in CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1 and NAMPT. Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity (PubMed:28683290). Represses the transcriptional activity of NR1I2 (PubMed:28751364).|||Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complexes, regulating the balance between degradation and stabilization. The SCF(FBXL3) complex is mainly nuclear and mediates ubiquitination and subsequent degradation of CRY2. In contrast, cytoplasmic SCF(FBXL21) complex-mediated ubiquitination leads to stabilize CRY2 and counteract the activity of the SCF(FBXL3) complex. The SCF(FBXL3) and SCF(FBXL21) complexes probably mediate ubiquitination at different Lys residues. The SCF(FBXL3) complex recognizes and binds CRY2 phosphorylated at Ser-553 and Ser-557. Ubiquitination may be inhibited by PER2. Deubiquitinated by USP7 (PubMed:27123980). http://togogenome.org/gene/10090:Slx4 ^@ http://purl.uniprot.org/uniprot/Q6P1D7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLX4 family.|||Forms a heterodimer with SLX1A/GIYD1. Interacts with ERCC4/XPF; catalytic subunit of the ERCC4-ERCC1 endonuclease. Interacts with MUS81; catalytic subunit of the MUS81-EME1 endonuclease. Interacts with MSH2; component of the MSH2-MSH3 mismatch repair complex. Interacts with TERF2-TERF2IP. Interacts with PLK1 and SLX4IP (By similarity).|||Highly expressed in testis. Expressed in bone marrow, brain, thymus and weakly in heart, kidney and spleen.|||Nucleus|||Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks (By similarity). http://togogenome.org/gene/10090:Ccdc103 ^@ http://purl.uniprot.org/uniprot/Q9D9P2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC103/PR46b family.|||Cytoplasm|||Dynein-attachment factor required for cilia motility.|||Homodimer.|||flagellum http://togogenome.org/gene/10090:Itgb2 ^@ http://purl.uniprot.org/uniprot/P11835|||http://purl.uniprot.org/uniprot/Q542I8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin beta chain family.|||Both Ser-747 and Ser-758 become phosphorylated when T-cells are exposed to phorbol esters. Phosphorylation on Thr-760 (but not on Ser-758) allows interaction with 14-3-3 proteins.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. The ITGB2 beta subunit associates with the ITGAL, ITGAM, ITGAX or ITGAD alpha subunits. Found in a complex with CD177 and ITGAM/CD11b (By similarity). Interacts with FGR (PubMed:19903482). Interacts with COPS5 and RANBP9 (By similarity). Interacts with FLNA (via filamin repeats 4, 9, 12, 17, 19, 21, and 23) (By similarity). Interacts with THBD (By similarity).|||Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL (By similarity). Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity (By similarity). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (By similarity). Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation (PubMed:18587400). Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (By similarity). In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (By similarity). Integrin ITGAM/ITGB2 plays a critical role in mast cell development and in immune complex-mediated glomerulonephritis. Mice expressing a null mutation of the ITGAM subunit gene demonstrate increase in neutrophil accumulation, in response to a impaired degranulation and phagocytosis, events that apparently accelerate apoptosis in neutrophils. These mice develop obesity.|||Membrane|||Membrane raft|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site. http://togogenome.org/gene/10090:Ccsap ^@ http://purl.uniprot.org/uniprot/Q8QZT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with microtubules; the association occurs on polyglutamylated tubulin.|||Belongs to the CCSAP family.|||Plays a role in microtubule (MT) stabilization and this stabilization involves the maintenance of NUMA1 at the spindle poles. Colocalizes with polyglutamylated MTs to promote MT stabilization and regulate bipolar spindle formation in mitosis. Binding of CCSAP to centrosomes and the spindle around centrosomes during mitosis inhibits MT depolymerization, thereby stabilizing the mitotic spindle. May play a role in embryonic development. May be required for proper cilia beating (By similarity).|||axon|||centriole|||centrosome|||cilium|||cilium axoneme|||cilium basal body|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Dnajc6 ^@ http://purl.uniprot.org/uniprot/Q80TZ3 ^@ Disruption Phenotype|||Function|||Subunit ^@ Interacts with HSPA8/HSC70. Interacts with CLTC. Interacts with AP2A2 (By similarity).|||Mice have a high rate of early postnatal mortality, although surviving pups have a normal life span despite decreased body weight. Knockout animals have impaired synaptic vesicle recycling, with an increased number of clathrin-coated vesicles, and impaired clathrin-mediated endocytosis of synaptic vesicles in neuronal culture. There is an up-regulation of Gak, but this does not fully compensate for the lack of the protein. The brains from mutant mice do not display alterations in substantia nigra morphology or dopamine transporter abundance or distribution, in agreement with the lack of gait or movement abnormalities in the mutant animals.|||Recruits HSPA8/HSC70 to clathrin-coated vesicles and promotes uncoating of clathrin-coated vesicles. Plays a role in clathrin-mediated endocytosis in neurons. http://togogenome.org/gene/10090:Rpe ^@ http://purl.uniprot.org/uniprot/B2KGF0|||http://purl.uniprot.org/uniprot/Q8VEE0 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the ribulose-phosphate 3-epimerase family.|||Binds 1 divalent metal cation per subunit.|||Binds 1 divalent metal cation per subunit. Active with Fe(2+), and probably also with Mn(2+), Zn(2+) and Co(2+).|||Catalyzes the reversible epimerization of D-ribulose 5-phosphate to D-xylulose 5-phosphate.|||Homodimer. http://togogenome.org/gene/10090:Rps6ka4 ^@ http://purl.uniprot.org/uniprot/Q9Z2B9 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by further autophosphorylation of Ser-196, Ser-360 and Ser-365 by the activated C-terminal kinase domain.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Enzyme activity requires the presence of both kinase domains.|||Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells which transiently dissociates following mitogenic stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA4 associates with and phosphorylates the NF-kappa-B p65 subunit RELA (By similarity).|||Nucleus|||Ser-343 and Thr-568 phosphorylation is required for kinase activity. Ser-343 and Ser-196 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-343, Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase domain (By similarity).|||Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). http://togogenome.org/gene/10090:Gm5935 ^@ http://purl.uniprot.org/uniprot/Q497S0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Hmx2 ^@ http://purl.uniprot.org/uniprot/P43687 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HMX homeobox family.|||Expressed in the developing CNS, including a specific expression in vestibular structures throughout inner ear development.|||It is expressed in neuronal and neuroepithelial cells during development of the CNS and PNS.|||Mice display a perturbation in cell fate determination in the lateral aspect of the otic epithelium results in reduced cell proliferation in epithelial cells, which includes the vestibular sensory patches and semicircular duct fusion plates, as well as in the adjacent mesenchyme. Consequently, enlargement and morphogenesis of the pars superior of the otocyst to form a complex labyrinth of cavities and ducts is blocked, as indicated by the lack of any distinguishable semicircular ducts, persistence of the primordial vestibular diverticula, significant loss in the 3 cristae and the macula utriculus, and a fused utriculosaccular chamber. Mice lacking both Hmx2 and Hmx3 show a complete loss of balance, postnatal dwarfism, defects in neuroendocrine system, disturbed hypothalamic-pituitary axis and subsequent die. Defects caused in mice lacking both Hmx2 and Hmx3 can be rescued by expressing the Drosophila Hmx protein.|||Nucleus|||Transcription factor involved in specification of neuronal cell types and which is required for inner ear and hypothalamus development. http://togogenome.org/gene/10090:Zfp42 ^@ http://purl.uniprot.org/uniprot/P22227 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in the inner cell mass of 4.5 dpc blastocysts, as well as in the polar trophoblast. At 6 dpc, abundant in the extraembryonic ectoderm and the ectoplacental cone. At this stage, not detected in the embryonic ectoderm. At 7 dpc, restricted to the extraembryonic ectoderm and the ectoplacental cone. Also expressed in the placenta. Expressed in male germ cells undergoing meiosis.|||Involved in the reprogramming of X-chromosome inactivation during the acquisition of pluripotency. Required for efficient elongation of TSIX, a non-coding RNA antisense to XIST. Binds DXPas34 enhancer within the TSIX promoter. Involved in ES cell self-renewal.|||Nucleus|||Polyubiquitinated by RNF12, leading to proteasomal degradation.|||Restricted to testis, to germ cells in the early stages of spermatogenesis. Not expressed in spermatids, nor spermatozoa. Expressed in embryonic stem (ES) cells.|||Up-regulated by NANOG, up-regulation which is increased by SOX2 and POU5F1. Up-regulated by nicotine; up-regulation which is prevented with tubocurarine, a nicotinic acetylcholine receptor antagonist. Down-regulated by sodium vanadate and retinoic acid (RA). In ES cells, down-regulation correlates with differentiation. http://togogenome.org/gene/10090:Traf3ip2 ^@ http://purl.uniprot.org/uniprot/Q8N7N6 ^@ Function|||Subunit ^@ E3 ubiquitin ligase that catalyzes 'Lys63'-linked polyubiquitination of target protein, enhancing protein-protein interaction and cell signaling (By similarity). Transfers ubiquitin from E2 ubiquitin-conjugating enzyme UBE2V1-UBE2N to substrate protein (By similarity). Essential adapter molecule in IL17A-mediated signaling (PubMed:19825828). Upon IL17A stimulation, interacts with IL17RA and IL17RC receptor chains through SEFIR domains and catalyzes 'Lys63'-linked polyubiquitination of TRAF6, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways (PubMed:19825828).|||Interacts with IKBKG/NF-kappa B essential modulator, with CHUK/IKK-alpha and with IKBKB/IKK-beta (By similarity). Interacts with TRAF6; this interaction is direct (PubMed:19825828). Interacts with IL17RA and IL17RC (PubMed:19825828, PubMed:33723527). Interacts with IL17RB (By similarity). http://togogenome.org/gene/10090:Nav3 ^@ http://purl.uniprot.org/uniprot/A0A668KM70|||http://purl.uniprot.org/uniprot/E9QMF5 ^@ Similarity ^@ Belongs to the Nav/unc-53 family. http://togogenome.org/gene/10090:Hs3st4 ^@ http://purl.uniprot.org/uniprot/D3YVV6 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Atic ^@ http://purl.uniprot.org/uniprot/Q9CWJ9 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AMP and XMP inhibit AICAR formyltransferase activity (By similarity). AICAR formyltransferase activity is inhibited by N-(6-fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5- [(3R)-3-hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), which acts as a tumor suppression in cancer cell lines (PubMed:29072452).|||Belongs to the PurH family.|||Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:29072452). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:29072452). Also displays cyclohydrolase activity involving the cyclization of FAICAR to IMP. Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction. Also catalyzes the cyclization of FAICAR to IMP. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (By similarity).|||Homodimer. Associates with internalized INSR complexes on Golgi/endosomal membranes. Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis.|||The IMP cyclohydrolase activity resides in the N-terminal region.|||The de novo purine synthesis pathway includes 10 sequential steps, beginning with phosphoribosyl pyrophosphate and ending with inositol monophosphate (IMP), the first purin compound of the pathway.|||cytosol http://togogenome.org/gene/10090:Ctcf ^@ http://purl.uniprot.org/uniprot/Q61164 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTCF zinc-finger protein family.|||Chromatin binding factor that binds to DNA sequence specific sites. Involved in transcriptional regulation by binding to chromatin insulators and preventing interaction between promoter and nearby enhancers and silencers. Acts as transcriptional repressor binding to promoters of vertebrate MYC gene and BAG1 gene. Also binds to the PLK and PIM1 promoters. Acts as a transcriptional activator of APP. Regulates APOA1/C3/A4/A5 gene cluster and controls MHC class II gene expression. Plays an essential role in oocyte and preimplantation embryo development by activating or repressing transcription. Seems to act as tumor suppressor. Plays a critical role in the epigenetic regulation. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, binding within the H19 imprinting control region (ICR) mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to IGF2. Plays a critical role in gene silencing over considerable distances in the genome. Preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation and maintaining methylation-free zones. Inversely, binding to target sites is prevented by CpG methylation. Plays an important role in chromatin remodeling. Can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping (By similarity). Mediates interchromosomal association between IGF2/H19 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory. Causes local loss of histone acetylation and gain of histone methylation in the beta-globin locus, without affecting transcription. When bound to chromatin, it provides an anchor point for nucleosomes positioning. Seems to be essential for homologous X-chromosome pairing. May participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation. May play a role in preventing the propagation of stable methylation at the escape genes from X-inactivation. Involved in sister chromatid cohesion. Associates with both centromeres and chromosomal arms during metaphase and required for cohesin localization to CTCF sites. Regulates asynchronous replication of IGF2/H19. Plays a role in the recruitment of CENPE to the pericentromeric/centromeric regions of the chromosome during mitosis (By similarity).|||Chromosome|||Interacts with CHD8 (PubMed:16949368). Interacts with LLPH (PubMed:26961175). Interacts with CENPE (By similarity).|||Sumoylated on Lys-74 and Lys-698; sumoylation of CTCF contributes to the repressive function of CTCF on the MYC P2 promoter.|||centromere|||nucleoplasm http://togogenome.org/gene/10090:Slc39a3 ^@ http://purl.uniprot.org/uniprot/A0A452J893|||http://purl.uniprot.org/uniprot/Q99K24 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Expressed very early during development of the mouse embryo. Expression is higher in testes, ovary, and the developing nervous system relative to other tissues.|||Highly expressed in the testes (PubMed:14525987). Highly expressed in dentate gyrus granule cells of the hippocampus (PubMed:35169020). Expressed in the mammary gland (PubMed:19458277).|||Knockout mice are viable and fertile and under normal growth conditions exhibit no obvious phenotypic abnormalities, and are only slightly more susceptible to the effects of dietary zinc deficiency.|||Membrane|||Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space (PubMed:14525987, PubMed:15634741, PubMed:35169020). Controls Zn(2+) accumulation into dentate gyrus granule cells in the hippocampus (PubMed:35169020). Mediates Zn(2+) reuptake from the secreted milk within the alveolar lumen (PubMed:19458277). http://togogenome.org/gene/10090:Mfsd6 ^@ http://purl.uniprot.org/uniprot/D3Z183|||http://purl.uniprot.org/uniprot/Q8CBH5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. MFSD6 family.|||MHC class I receptor. Binds only to H-2 class I histocompatibility antigen, K-D alpha chain (H-2K(D)).|||Membrane http://togogenome.org/gene/10090:Ndc80 ^@ http://purl.uniprot.org/uniprot/Q9D0F1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-53 and Lys-59 by KAT5 during mitosis, promoting robust kinetochore-microtubule attachment. Deacetylated by SIRT1.|||Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules.|||Belongs to the NDC80/HEC1 family.|||Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end. Interacts with NEK2 and ZWINT specifically during mitosis. Interacts with CENPH and MIS12. May interact with AURKB, PSMC2, PSMC5 and SMC1A. May interact with RB1 during G2 phase and mitosis. Interacts with CKAP5 (By similarity). Interacts with CDT1; leading to kinetochore localization of CDT1 (By similarity).|||Expressed in spleen, testis and thymus.|||Nucleus|||Phosphorylation begins in S phase of the cell cycle and peaks in mitosis. Phosphorylated by NEK2. Also phosphorylated by AURKA and AURKB.|||kinetochore http://togogenome.org/gene/10090:Lmbrd1 ^@ http://purl.uniprot.org/uniprot/Q8K0B2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LIMR family. LMBRD1 subfamily.|||Cell membrane|||Early embryonic lethality (PubMed:27061115). Embryos show an impaired initiation of gastrulation (PubMed:27061115).|||Endoplasmic reticulum membrane|||Interacts with ABCD4; this interaction induces the translocation of ABCD4 from the endoplasmic reticulum to the lysosome. Interacts with ABCD4 and MMACHC; this interaction ensures the transport of cobalamin from the lysosome to the cytoplasm (By similarity). Interacts with INSR, adapter protein complex 2 and clathrin heavy chain (PubMed:24078630).|||Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors. Targets ABCD4 transporter from the endoplasmic reticulum to the lysosome. Then forms a complex with lysosomal ABCD4 and cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane (By similarity). Acts as an adapter protein which plays an important role in mediating and regulating the internalization of the insulin receptor (INSR) (PubMed:24078630). Involved in clathrin-mediated endocytosis of INSR via its interaction with adapter protein complex 2 (PubMed:24078630). Essential for the initiation of gastrulation and early formation of mesoderm structures during embryogenesis (PubMed:27061115).|||Lysosome membrane|||N-glycosylated.|||Ubiquitously expressed with strong signals in the primitive streak and in extraembryonic tissues at 7.5 dpc (PubMed:27061115). During further development, expression is strongest in the neuronal fold at 8.5 dpc (PubMed:27061115).|||clathrin-coated vesicle http://togogenome.org/gene/10090:Mthfd1 ^@ http://purl.uniprot.org/uniprot/Q3TW74|||http://purl.uniprot.org/uniprot/Q8BXX7|||http://purl.uniprot.org/uniprot/Q922D8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer.|||In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.|||In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.|||The N-terminal methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase (D/C) domain carries both the methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities.|||The larger C-terminal formyltetrahydrofolate synthetase domain carries a third formyltetrahydrofolate synthetase activity.|||Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate. These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance. http://togogenome.org/gene/10090:Wfdc11 ^@ http://purl.uniprot.org/uniprot/A2A5H7 ^@ Miscellaneous|||Subcellular Location Annotation ^@ Although this protein was isolated in a region containing several WAP proteins and was defined as a WAP protein, it does not contain a classical WAP domain.|||Secreted http://togogenome.org/gene/10090:Gsg1l ^@ http://purl.uniprot.org/uniprot/D3Z7H4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the inner core of AMPAR complexes, modifies AMPA receptor (AMPAR) gating.|||Belongs to the GSG1 family.|||Cell membrane|||Component of the inner core of AMPAR complexes. AMPAR complexes consist of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complexes is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complexes and profoundly impact their biogenesis and protein processing.|||Expressed in the brain, including hippocampus (at protein level).|||Synapse http://togogenome.org/gene/10090:Lhfpl1 ^@ http://purl.uniprot.org/uniprot/Q80SV1 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LHFP family.|||Membrane|||Widely expressed (PubMed:26964900). Strongly expressed in vagina and ovary. Weakly expressed in spleen, kidney, thymus, testis, brain, lung, intestine and uterus (PubMed:26964900). http://togogenome.org/gene/10090:Kank3 ^@ http://purl.uniprot.org/uniprot/Q9Z1P7 ^@ Function ^@ May be involved in the control of cytoskeleton formation by regulating actin polymerization. http://togogenome.org/gene/10090:Atg3 ^@ http://purl.uniprot.org/uniprot/Q9CPX6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATG3 family.|||Cleaved by CASP8 upon death ligand binding such as tumor necrosis factor-alpha. CASP8 cleavage blocks survival-related autophagy and favors apoptosis (By similarity).|||Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a role in regulation of mitochondrial homeostasis and cell death, while it is not involved in PE-conjugation to ATG8-like proteins and autophagy.|||Cytoplasm|||E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3. ATG12-ATG3 conjugate is also formed upon viccina virus infection, leading to the disruption the cellular autophagy which is not necessary for vaccinia survival and proliferation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.|||Interacts with ATG7 and ATG12. The complex composed of ATG3 and ATG7 plays a role in the conjugation of ATG12 to ATG5. Interacts with FNBP1L (By similarity). http://togogenome.org/gene/10090:Sprr3 ^@ http://purl.uniprot.org/uniprot/O09116 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes.|||Cytoplasm http://togogenome.org/gene/10090:Dda1 ^@ http://purl.uniprot.org/uniprot/D3YXY5|||http://purl.uniprot.org/uniprot/Q9D9Z5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DDA1 family.|||Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1. Component of the DCX(DCAF15) complex, also named CLR4(DCAF15) complex, composed of DCAF15, DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1. Part of the DDD core complex containing DET1, DDA1 and DDB1; the DDD core complex recruits a specific UBE2E enzyme, such as UBE2E1, UBE2E2 UBE2E3, to form specific DDD-E2 complexes.|||Functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. In the DCX complexes, acts as a scaffolding subunit required to stabilize the complex. http://togogenome.org/gene/10090:Cldn34d ^@ http://purl.uniprot.org/uniprot/A2AGU5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Rhox3h ^@ http://purl.uniprot.org/uniprot/L7MU37 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Enpp1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Q7|||http://purl.uniprot.org/uniprot/G3X9S2|||http://purl.uniprot.org/uniprot/P06802 ^@ Activity Regulation|||Caution|||Cofactor|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At low concentrations of ATP, a phosphorylated intermediate is formed which inhibits further hydrolysis.|||Basolateral cell membrane|||Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||Defects in Enpp1 are the cause of spontaneous asj-2J mutant characterized by gait due to stiffening of the joints (PubMed:25479107). Defects are caused by a significant reduction in the plasma diphosphate (PPi) concentration, leading to extensive aberrant mineralization affecting the arterial vasculature, a number of internal organs and the dermal sheath of vibrissae (PubMed:25479107). Asj-2J mice are used as a model for arterial calcification of infancy disorder (GACI1) (PubMed:25479107). Mice also show ectopic mineralization of cartilage and collagen-rich tendons and ligaments (PubMed:26910915).|||Defects in Enpp1 are the cause of the tiptoe walking (ttw) phenotype. Ttw mice exhibit ossification of the spinal ligaments (PubMed:9662402). Mice display increased bone formation process in joints and develop spontaneous osteoarthritis-like changes (PubMed:22510396).|||Ectonucleotide pyrophosphatase/phosphodiesterase family member 1: Homodimer (PubMed:23027977, PubMed:23041369). Ectonucleotide pyrophosphatase/phosphodiesterase family member 1: Interacts with INSR; leading to inhibit INSR autophosphorylation and subsequent activation of INSR kinase activity (By similarity). Ectonucleotide pyrophosphatase/phosphodiesterase family member 1, secreted form: Monomeric (PubMed:23041369).|||It is uncertain whether Met-1 or Met-35 is the initiator.|||Mice show ectopic calcification of articular cartilage, the joint capsule and certain tendons (PubMed:25260930). Mice also display calcification of the joints and vertebrae as well as soft tissues including the whisker follicles, ear pinna and trachea (PubMed:25260930). This calcification worsened as the animals aged (PubMed:25260930). Bone mineralization in mice lacking both Enpp1 and Alpl is essentially normal, demonstrating that Enpp1 and Alpl are antagonist key regulators of bone mineralization by determining the normal steady-state levels of diphosphate (PPi) (PubMed:12082181). Bones and plasma of deficient mice are almost devoid of PPi.|||N-glycosylated.|||Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels (PubMed:9662402, PubMed:10352096, PubMed:11004006, PubMed:12082181, PubMed:22510396, PubMed:25260930). PPi inhibits bone mineralization and soft tissue calcification by binding to nascent hydroxyapatite crystals, thereby preventing further growth of these crystals (PubMed:9662402, PubMed:10352096, PubMed:11004006, PubMed:12082181, PubMed:19419305, PubMed:22510396, PubMed:25260930, PubMed:25479107, PubMed:26910915, PubMed:30111653, PubMed:35147247). Preferentially hydrolyzes ATP, but can also hydrolyze other nucleoside 5' triphosphates such as GTP, CTP and UTP to their corresponding monophosphates with release of pyrophosphate, as well as diadenosine polyphosphates, and also 3',5'-cAMP to AMP (PubMed:11027689, PubMed:1647027, PubMed:23027977, PubMed:8223581). May also be involved in the regulation of the availability of nucleotide sugars in the endoplasmic reticulum and Golgi, and the regulation of purinergic signaling (PubMed:1647027). Inhibits ectopic joint calcification and maintains articular chondrocytes by repressing hedgehog signaling; it is however unclear whether hedgehog inhibition is direct or indirect (PubMed:30111653). Appears to modulate insulin sensitivity (By similarity). Also involved in melanogenesis (By similarity). Also able to hydrolyze 2',3'-cGAMP (cyclic GMP-AMP), a second messenger that activates TMEM173/STING and triggers type-I interferon production (PubMed:25344812). 2',3'-cGAMP degradation takes place in the lumen or extracellular space, and not in the cytosol where it is produced; the role of 2',3'-cGAMP hydrolysis is therefore unclear (By similarity). Not able to hydrolyze the 2',3'-cGAMP linkage isomer 3',3'-cGAMP (By similarity).|||Secreted|||Selectively expressed on the surface of antibody-secreting cells (PubMed:3104326). Expressed in osteocytes and osteoclasts (PubMed:25260930).|||The di-leucine motif is required for basolateral targeting in polarized epithelial cells, and for targeting to matrix vesicles derived from mineralizing cells.|||The secreted form is produced through cleavage at Lys-85 by intracellular processing. http://togogenome.org/gene/10090:Sorcs3 ^@ http://purl.uniprot.org/uniprot/Q1HL22|||http://purl.uniprot.org/uniprot/Q8VI51 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the VPS10-related sortilin family. SORCS subfamily.|||Membrane http://togogenome.org/gene/10090:Slc10a5 ^@ http://purl.uniprot.org/uniprot/Q5PT54 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Membrane http://togogenome.org/gene/10090:Cirbp ^@ http://purl.uniprot.org/uniprot/P60824 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both the RRM domain and the arginine, glycine (RGG) rich domain are necessary for binding to the TXN 3'-untranslated region (By similarity). Both the RRM domain and the arginine, glycine (RGG) rich domain (RGG repeats) are necessary for optimal recruitment into SGs upon cellular stress. The C-terminal domain containing RGG repeats is necessary for translational repression.|||Cold-inducible mRNA binding protein that plays a protective role in the genotoxic stress response by stabilizing transcripts of genes involved in cell survival. Promotes assembly of stress granules (SGs), when overexpressed. Seems to play an essential role in cold-induced suppression of cell proliferation. Acts as a translational repressor. Acts as a translational activator. Binds specifically to the 3'-untranslated regions (3'-UTRs) of stress-responsive transcripts RPA2 and TXN.|||Cytoplasm|||Interacts with EIF4G1. Associates with ribosomes (By similarity).|||Methylated on arginine residues. Methylation of the RGG motifs is a prerequisite for recruitment into SGs.|||Phosphorylated by CK2, GSK3A and GSK3B. Phosphorylation by GSK3B increases RNA-binding activity to the TXN 3'-UTR transcript upon exposure to UV radiation (By similarity).|||Ubiquitous.|||Up-regulated upon mild cold-shock and hypoxia.|||nucleoplasm http://togogenome.org/gene/10090:Tesl1 ^@ http://purl.uniprot.org/uniprot/B1AXB9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the prickle / espinas / testin family.|||Cytoplasm|||focal adhesion http://togogenome.org/gene/10090:Med8 ^@ http://purl.uniprot.org/uniprot/Q9CY05|||http://purl.uniprot.org/uniprot/Q9D7W5|||http://purl.uniprot.org/uniprot/Q9DAY7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 8 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May play a role as a target recruitment subunit in E3 ubiquitin-protein ligase complexes and thus in ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May play a role as a target recruitment subunit in E3 ubiquitin-protein ligase complexes and thus in ubiquitination and subsequent proteasomal degradation of target proteins.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. May be part of a multisubunit E3 ubiquitin-protein ligase complex with the Elongin BC complex (ELOB and ELOC), CUL2 and RBX1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Taf7l ^@ http://purl.uniprot.org/uniprot/B1AV36|||http://purl.uniprot.org/uniprot/Q9D3R9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TAF7 family.|||Cytoplasm|||Nucleus|||Probably functions as a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. May play a role in spermatogenesis.|||Reduced sperm count and motility.|||TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TAF7L may replace TAF7 in a spermatogenesis-specific form of TFIID. Interacts with TBP; the interaction occurs in a sub-population of cells (pachytene and haploid round spermatids) and is developmentally regulated through differential intracellular localization of the two proteins. Interacts with TAF1.|||Testis-specific (at protein level). Expressed during spermatogenesis from spermatogonia stage up to the stage of round spermatids. http://togogenome.org/gene/10090:St3gal1 ^@ http://purl.uniprot.org/uniprot/P54751|||http://purl.uniprot.org/uniprot/Q544T4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A beta-galactoside alpha2-3 sialyltransferase involved in terminal sialylation of glycoproteins and glycolipids (PubMed:8375377, PubMed:9184827). Catalyzes the transfer of sialic acid (N-acetyl-neuraminic acid; Neu5Ac) from the nucleotide sugar donor CMP-Neu5Ac onto acceptor Galbeta-(1->3)-GalNAc-terminated glycoconjugates through an alpha2-3 linkage (PubMed:8144500, PubMed:8375377, PubMed:9184827, PubMed:10755614). Adds sialic acid to the core 1 O-glycan, Galbeta-(1->3)-GalNAc-O-Ser/Thr, which is a major structure of mucin-type O-glycans. As part of a homeostatic mechanism that regulates CD8-positive T cell numbers, sialylates core 1 O-glycans of T cell glycoproteins, SPN/CD43 and PTPRC/CD45. Prevents premature apoptosis of thymic CD8-positive T cells prior to peripheral emigration, whereas in the secondary lymphoid organs controls the survival of CD8-positive memory T cells generated following a successful immune response (PubMed:10755614). Transfers sialic acid to asialofetuin, presumably onto Galbeta-(1->3)-GalNAc-O-Ser (PubMed:8375377). Sialylates GM1a, GA1 and GD1b gangliosides to form GD1a, GM1b and GT1b, respectively (PubMed:8144500, PubMed:8375377, PubMed:9184827).|||Belongs to the glycosyltransferase 29 family.|||Golgi stack membrane|||Highly expressed in submaxillary gland and to a much lesser extent in liver, lung, kidney, heart and brain.|||Knockout mice are deficient in CD8-positive T cells due to increased apoptosis. This is associated with a reduction of naive to memory T cells ratio in blood and peripheral lymphoid organs.|||Membrane|||Secreted|||The soluble form derives from the membrane form by proteolytic processing.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gm14692 ^@ http://purl.uniprot.org/uniprot/A2BH01 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Pcdha2 ^@ http://purl.uniprot.org/uniprot/Q05C01|||http://purl.uniprot.org/uniprot/Q91Y17 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Trim72 ^@ http://purl.uniprot.org/uniprot/Q1XH17 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasmic vesicle membrane|||Disulfide bond formation at Cys-242 occurs in case of membrane damage that cause the entry of the oxidized milieu of the extracellular space, resulting in homooligomerization.|||Homooligomer; disulfide-linked. Interacts with DYSF and CAV3.|||Muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Specifically binds phosphatidylserine. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)-dependent membrane resealing process. Required for transport of DYSF to sites of cell injury during repair patch formation. Regulates membrane budding and exocytosis. May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles.|||Muscle-specific. Exclusively expressed in cardiac and skeletal muscle.|||S-nitrosylation at Cys-144 stabilizes TRIM72 and protects against oxidation-induced protein degradation and cell death.|||Viable until at least 11 months of age under unstressed conditions, and develop progressive muscle pathology with age. Mice show progressive myopathy and reduced exercise capability, associated with defective membrane-repair capacity.|||sarcolemma http://togogenome.org/gene/10090:Zfp575 ^@ http://purl.uniprot.org/uniprot/Q3TXZ1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Or4p18 ^@ http://purl.uniprot.org/uniprot/A2AUS6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Igfl3 ^@ http://purl.uniprot.org/uniprot/Q6B9Z0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IGFL family.|||Highly expressed in skin. Also detected in colon, thymus, mammary gland, lymph node and lung.|||Homodimer; disulfide-linked.|||Probable ligand of the IGFLR1 cell membrane receptor.|||Secreted|||Up-regulated by Imiquimod. Up-regulated in skin upon tissue inflammation and injury. http://togogenome.org/gene/10090:Enkur ^@ http://purl.uniprot.org/uniprot/Q4KL11|||http://purl.uniprot.org/uniprot/Q6SP97 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter that functions to localize a calcium-sensitive signal transduction machinery in sperm to a calcium-permeable ion channel (PubMed:15385169). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity).|||Binds calmodulin via its IQ domain. Interacts with TRPC1, TRPC2, TRPC5, but not TRPC3 (PubMed:15385169). Interacts with CFAP45 (By similarity).|||High expression in testis and vomeronasal organ and lower expression in ovary, heart, lung, and brain. Not expressed in other tissues.|||The IQ motif is involved in calmodulin binding.|||cilium axoneme|||flagellum http://togogenome.org/gene/10090:Sox2 ^@ http://purl.uniprot.org/uniprot/P48432|||http://purl.uniprot.org/uniprot/Q60I23 ^@ Biotechnology|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By SRRT.|||Cytoplasm|||Embryonically lethal.|||Expressed in the basal cells of the tongue epithelium at birth until P20 (PubMed:32758484). Expressed in the suprabasal cells of the buccal mucosa and esophagus at P20 (PubMed:32758484).|||Expressed in the cochlea (at protein level) (PubMed:32127020). Expressed in the brain and retina (PubMed:7590241, PubMed:15863505). A very low level of expression is seen in the stomach and lung (PubMed:7590241, PubMed:15863505). Expressed in the kidney (PubMed:15863505).|||Interacts with ZSCAN10 (PubMed:19740739). Interacts with SOX3 and FGFR1 (PubMed:17728342). Interacts with GLIS1 (By similarity). Interacts with POU5F1; binds synergistically with POU5F1 to DNA (PubMed:15863505). Interacts with DDX56 (PubMed:32703285). Interacts with L3MBTL3 and DCAF5 (PubMed:30442713). The interaction with L3MBTL3 and DCAF5 requires methylation at Lys-44 and is necessary to target SOX2 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex (By similarity). Interacts with RCOR1/CoREST (PubMed:30442713). Interacts with PHF20L1 (PubMed:29358331). The interaction with PHF20L1 requires methylation at Lys-44 and Lys-119 and protects SOX2 from degradation (By similarity). Interacts with TRIM26; this interaction prevents ubiquitination by WWP2 (By similarity).|||Methylation at Lys-44 and Lys-119 is necessary for the regulation of SOX2 proteasomal degradation.|||Nucleus|||POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.|||Sumoylation inhibits binding on DNA and negatively regulates the FGF4 transactivation.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor that forms a trimeric complex with POU5F1 (OCT3/4) on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (PubMed:15863505, PubMed:17097055, PubMed:19740739, PubMed:32703285). Binds to the proximal enhancer region of NANOG (PubMed:15863505). Critical for early embryogenesis and for embryonic stem cell pluripotency (By similarity). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (PubMed:22198669). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). May function as a switch in neuronal development (By similarity).|||Ubiquitinated by WWP2, leading to proteasomal degradation. http://togogenome.org/gene/10090:Mllt3 ^@ http://purl.uniprot.org/uniprot/A2AM29 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Specifically recognizes and binds acylated histone H3, with a preference for histone H3 that is crotonylated. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. Recognizes and binds histone H3 crotonylated at 'Lys-9' (H3K9cr), and with slightly lower affinity histone H3 crotonylated at 'Lys-18' (H3K18cr). Also recognizes and binds histone H3 acetylated and butyrylated at 'Lys-9' (H3K9ac and H3K9bu, respectively), but with lower affinity than crotonylated histone H3. In the SEC complex, MLLT3 is required to recruit the complex to crotonylated histones. Recruitment of the SEC complex to crotonylated histones promotes recruitment of DOT1L on active chromatin to deposit histone H3 'Lys-79' methylation (H3K79me). Plays a key role in hematopoietic stem cell (HSC) maintenance by preserving, rather than confering, HSC stemness. Acts by binding to the transcription start site of active genes in HSCs and sustaining level of H3K79me2, probably by recruiting DOT1L.|||Chromosome|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3) (By similarity). Interacts with BCOR (By similarity). Interacts with CBX8 (PubMed:11439343). Interacts with ALKBH4 (By similarity).|||Nucleus|||The YEATS domain specifically recognizes and binds acylated histones, with a marked preference for histones that are crotonylated. Also binds histone H3 acetylated at 'Lys-9' (H3K9ac), but with lower affinity. Binds crotonylated lysine through a non-canonical pi-pi-pi stacking mechanism. The YEATS domain also binds DNA.|||Ubiquitously expressed. Strong expression in the spleen. http://togogenome.org/gene/10090:Grm5 ^@ http://purl.uniprot.org/uniprot/B2BH30|||http://purl.uniprot.org/uniprot/B7ZMP7|||http://purl.uniprot.org/uniprot/E9QMC2|||http://purl.uniprot.org/uniprot/Q3UVX5|||http://purl.uniprot.org/uniprot/Q4VA56 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity (By similarity).|||Membrane|||The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3 (By similarity). Interacts with SIAH1 and TAMALIN. Interacts with NCDN. Interacts with NECAB2 (By similarity). Interacts with CAMK2A (By similarity). http://togogenome.org/gene/10090:Smtnl2 ^@ http://purl.uniprot.org/uniprot/Q8CI12 ^@ Similarity ^@ Belongs to the smoothelin family. http://togogenome.org/gene/10090:Pglyrp4 ^@ http://purl.uniprot.org/uniprot/B7ZMZ4|||http://purl.uniprot.org/uniprot/Q0VB07 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.|||Homodimer; disulfide-linked. Heterodimer with PGLYRP3; disulfide-linked (By similarity).|||Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Binds also to Gram-negative bacteria, and has bacteriostatic activity towards Gram-negative bacteria. Plays a role in innate immunity (By similarity).|||Secreted|||Ubiquitous. http://togogenome.org/gene/10090:Slc25a45 ^@ http://purl.uniprot.org/uniprot/A0A494BAQ4|||http://purl.uniprot.org/uniprot/Q8CFJ7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Membrane|||Mitochondrion inner membrane|||Widely expressed, with highest levels in testis, liver and kidney and low levels in brain, including cortex, cerebellum, hippocampus and hypothalamus, and heart. http://togogenome.org/gene/10090:Dlc1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J171|||http://purl.uniprot.org/uniprot/D5M8I5|||http://purl.uniprot.org/uniprot/E9PXD2|||http://purl.uniprot.org/uniprot/E9QKB1|||http://purl.uniprot.org/uniprot/Q9R0Z9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality (By similarity). Required for growth factor-induced epithelial cell migration; in resting cells, interacts with TNS3 while PTEN interacts with the p85 regulatory subunit of the PI3K kinase complex but growth factor stimulation induces phosphorylation of TNS3 and PTEN, causing them to change their binding preference so that PTEN interacts with DLC1 and TNS3 interacts with p85 (By similarity). The PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA while the TNS3-p85 complex translocates to the leading edge of migrating cells to promote RAC1 activation (By similarity).|||Interacts with EF1A1, facilitates EF1A1 distribution to the membrane periphery and ruffles upon growth factor stimulation and suppresses cell migration. Interacts with tensin TNS1 (via N-terminus); the interaction is decreased by phosphorylation of TNS1. Interacts with TNS3 and PTEN; in resting cells, interacts with TNS3 (via C2 tensin-type domain) but, following growth factor stimulation, TNS3 and PTEN are phosphorylated which leads to weakened interaction with TNS3 and enhanced interaction with PTEN. Interacts (via C-terminus) with tensin TNS4 (via SH2 domain); the interaction is independent of tyrosine phosphorylation of DLC1.|||Membrane|||The SAM domain mediates interaction with EF1A1, and functions as an autoinhibitory regulator of RhoGAP Activity.|||The polybasic cluster is required for activation and mediates binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) containing membranes.|||Widely expressed with the highest levels in heart, liver and lung.|||focal adhesion http://togogenome.org/gene/10090:Crygd ^@ http://purl.uniprot.org/uniprot/P04342 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Detected in the superior olivary complex of the auditory hindbrain.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||There are six different gamma crystallins identified in mouse lens. http://togogenome.org/gene/10090:Slc8a1 ^@ http://purl.uniprot.org/uniprot/A0A3Q4EBU5|||http://purl.uniprot.org/uniprot/G3X9J1|||http://purl.uniprot.org/uniprot/P70414|||http://purl.uniprot.org/uniprot/Q27PY9|||http://purl.uniprot.org/uniprot/Q68FL0 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by micromolar levels of Ca(2+).|||At 9.5 dpc, expression is restricted to the embryonic heart, and is not detectable in any other part of the body.|||Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.|||Cell membrane|||Complete embryonic lethality at about 9.5 dpc. At 9.5 dpc, mutant embryos display strongly decreased body size, an absence of blood vessels in the vitelline sac, and defective heart beat. Contrary to wild type hearts that show regular contractions, about 70% of the mutants have no spontaneous contractions of the heart, and the remainder show only very slow and arrhythmic heart contractions. Mutant hearts have thinner ventricles, contain fewer cardiac myocytes, and display an increased number of apoptotic cells. Mutant hearts do not show fast Ca(2+) transients and display lack of sodium/calcium exchange activity. In mutant hearts, caffeine stimulates normal release of intracellular Ca(2+) stores from the endoplasmic reticulum into the cytoplasm, but the subsequent decrease of the high cytoplasmic Ca(2+) levels is impaired (PubMed:10967099). At 9.5 dpc, embryonic cardiomyocytes show severe disorganization of the myofibrils and swollen mitochondria (PubMed:12781968).|||Detected in heart, kidney and brain (at protein level).|||Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:8659820). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle (PubMed:8659820). In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum (PubMed:8659820). SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline (PubMed:10967099). Required for normal embryonic heart development and the onset of heart contractions (PubMed:10967099).|||Membrane|||The cytoplasmic Calx-beta domains bind the regulatory Ca(2+). The first Calx-beta domain can bind up to four Ca(2+) ions. The second domain can bind another two Ca(2+) ions that are essential for calcium-regulated ion exchange. http://togogenome.org/gene/10090:Ccdc18 ^@ http://purl.uniprot.org/uniprot/Q640L5 ^@ Subcellular Location Annotation ^@ centriolar satellite http://togogenome.org/gene/10090:Stk24 ^@ http://purl.uniprot.org/uniprot/Q99KH8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Membrane|||Monomer. Interacts with CTTNBP2NL. Interacts with RIPOR1 (via C-terminus); this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts with PDCD10; this interaction is required for the association of STK24 with RIPOR1.|||Nucleus|||Oxidative stress induces phosphorylation. Activated by autophosphorylation at Thr-178 and phosphorylation at this site is essential for its function. Manganese, magnesium and cobalt-dependent autophosphorylation is mainly on threonine residues while zinc-dependent autophosphorylation is on both serine and threonine residues (By similarity).|||Proteolytically processed by caspases during apoptosis. Proteolytic cleavage results in kinase activation, nuclear translocation of the truncated form (MST3/N) and the induction of apoptosis (By similarity).|||Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation. Regulates also cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. Acts as a key regulator of axon regeneration in the optic nerve and radial nerve (By similarity). http://togogenome.org/gene/10090:Sec14l1 ^@ http://purl.uniprot.org/uniprot/A8Y5H7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Golgi apparatus|||Interacts with RIGI (via tandem CARD domain); the interaction is direct. Interacts (via GOLD domain) with SLC18A3; the interaction is direct. Interacts with SLC5A7 (via GOLD domain); the interaction is direct.|||May play a role in innate immunity by inhibiting the antiviral RIG-I signaling pathway. In this pathway, functions as a negative regulator of RIGI, the cytoplasmic sensor of viral nucleic acids. Prevents the interaction of RIGI with MAVS/IPS1, an important step in signal propagation. May also regulate the SLC18A3 and SLC5A7 cholinergic transporters. http://togogenome.org/gene/10090:Ccdc154 ^@ http://purl.uniprot.org/uniprot/Q6RUT8 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Early endosome|||Expressed in brain, heart, lung, liver, spleen, kidney, testis, muscle, intestine and thymus. http://togogenome.org/gene/10090:Trip13 ^@ http://purl.uniprot.org/uniprot/Q3UA06 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family. PCH2 subfamily.|||Mice develop normally without obvious somatic defects but males and females are sterile due to meiotic disruption in meiocytes. Homozygous mutants display small gonads and females have few or no follicles, due to oocyte elimination between pachynema and dictyate. Mutant testes display reduced populated tubules and spermatogenesis is mainly arrested at spermatocyte stages of epithelial stage IV, corresponding to pachynema. Different phenotypes are observed in the different knockout experiments tested. In Trip13(RRB047) mutant mice, also named Trip13(mod) allele for moderate, the number of crossovers are not affected and meiocytes undergo homologous chromosome synapsis despide the presence of unrepaired DSBs in pachynema. Using a more severe mutant allele, named Trip13(sev) for severe, additional defects are observed: the numbers of crossovers and chiasmata are reduced in the absence of TRIP13, and their distribution along the chromosomes is altered (PubMed:20711356). Autosomal bivalents in meiocytes frequently display pericentric synaptic forks and other defects (PubMed:20711356). Recombination defects are evident very early in meiotic prophase, soon after DSB formation (PubMed:20711356). These results suggest that the absence of defects in the number of crossovers observed in Trip13(RRB047) mutant is due to the use of a weak hypomorphic mutant allele.|||Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways. Also required for development of higher-order chromosome structures and is needed for synaptonemal-complex formation. In males, required for efficient synapsis of the sex chromosomes and for sex body formation. Promotes early steps of the DNA double-strand breaks (DSBs) repair process upstream of the assembly of RAD51 complexes. Required for depletion of HORMAD1 and HORMAD2 from synapsed chromosomes (PubMed:17696610, PubMed:19851446, PubMed:20711356). Plays a role in mitotic spindle assembly checkpoint (SAC) activation (By similarity).|||Specifically interacts with the ligand binding domain of the thyroid receptor (TR). This interaction does not require the presence of thyroid hormone for its interaction (By similarity). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (PubMed:31437213).|||Widely expressed, including in testis. http://togogenome.org/gene/10090:Pafah1b2 ^@ http://purl.uniprot.org/uniprot/Q61206 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha2 catalytic subunit of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and modulates the action of PAF. The activity and substrate specificity of PAF-AH (I) are affected by its subunit composition. The alpha2/alpha2 homodimer (PAFAH1B2/PAFAH1B2 homodimer) hydrolyzes PAF and 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE) more efficiently than 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA). In contrast, the alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B3 heterodimer) hydrolyzes AAGPA more efficiently than PAF, but has little hydrolytic activity towards AAGPE (By similarity). May play a role in male germ cell meiosis during the late pachytenestage and meiotic divisions as well as early spermiogenesis (PubMed:12775763).|||Belongs to the 'GDSL' lipolytic enzyme family. Platelet-activating factor acetylhydrolase IB beta/gamma subunits subfamily.|||Beta subunit (PAFAH1B1) stimulates the acetylhydrolase activity of the alpha2/alpha2 catalytic homodimer.|||Cytoplasm|||Expressed already by the time of neurulation. By 10.5 dpc, expression is abundant in the developing central and peripheral nervous systems. Major sites include the neuroepithelium of the fore-, mid-, and hindbrain, the spinal cord, the dorsal root, and cranial ganglia.|||Forms a catalytic dimer which is either homodimer (alpha2/alpha2 homodimer) or heterodimer with PAFAH1B3 (alpha2/alpha1 heterodimer). Component of the cytosolic (PAF-AH (I)) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity (By similarity). Interacts (homodimer form) with PAFAH1B1 (homodimer form); PAFAH1B2 competes with NDEL1 for PAFAH1B1 binding (By similarity). Interacts with VLDLR; this interaction may modulate the Reelin pathway (PubMed:17330141).|||Knockout mice which are homozygous for the PAFAH1B2 gene appear developmentally normal, and are born at the expected Mendelian rate (PubMed:12775763). Females bred normally, whereas male are infertile, and spermatogenesis is disrupted at mid- or late pachytene stages of meiosis or early spermiogenesis (PubMed:12775763). Double mutant female mice which are homozygous for PAFAH1B2 and PAFAH1B3 are grossly normal and fertile, whereas double-mutant males are infertile. Double mutan mice manifest an earlier disturbance of spermatogenesis with an onset at preleptotene or leptotene stages of meiosis (PubMed:12775763).|||Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity). http://togogenome.org/gene/10090:Dmrt3 ^@ http://purl.uniprot.org/uniprot/Q80WT2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DMRT family.|||DMA domain interacts with ubiquitin.|||DMRT3 is a marker for a subset of spinal cord neurons (dI6).|||Expressed at 14.5 dpc in testis, kidney and bladder. Expression drops at 13.5 dpc in female gonads and is not detected at 15.5 dpc while it is expressed by Sertoli cells in testis.|||Expressed in the ventral spinal cord, in a restrical population of neurons migrating ventrically in the developing spinal cord at 11.5 dpc.|||Nucleus|||Probable transcription factor that plays a role in configuring the spinal circuits controlling stride in vertebrates. Involved in neuronal specification within specific subdivision of spinal cord neurons and in the development of a coordinated locomotor network controlling limb movements. May regulate transcription during sexual development.|||Significantly increase of stride length and extension movements in all limbs. Mice have major difficulties running at higher velocities. In water, mice spend less time swimming and showed frequent twitching limb movements. http://togogenome.org/gene/10090:Stox1 ^@ http://purl.uniprot.org/uniprot/B2RQL2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Detected in sensory epithelial cells of the inner ear but not in adjacent surrounding tissue (at protein level).|||Highly expressed at 14 dpc with lower levels at 18 dpc and P3.|||Involved in regulating the levels of reactive oxidative species and reactive nitrogen species and in mitochondrial homeostasis in the placenta (By similarity). Required for regulation of inner ear epithelial cell proliferation via the AKT signaling pathway (PubMed:25677106). Involved in cell cycle regulation by binding to the CCNB1 promoter, up-regulating its expression and promoting mitotic entry (By similarity). Induces phosphorylation of MAPT/tau (By similarity).|||Nucleus|||centrosome http://togogenome.org/gene/10090:Apex2 ^@ http://purl.uniprot.org/uniprot/A2AFM3|||http://purl.uniprot.org/uniprot/Q68G58 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3'-5' exonuclease activity is activated by sodium and manganese (By similarity). 3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA (By similarity).|||Belongs to the DNA repair enzymes AP/ExoA family.|||Cytoplasm|||Expressed in lymphocytes, thymocytes and splenocytes (at protein level). Highly expressed in the thymus and weakly expressed in the bone marrow, spleen, eye, kidney, lung, brain and uterus.|||Functions as a weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents (By similarity). Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends (By similarity). Also displays double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities. Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially (By similarity). Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents. In the nucleus functions in the PCNA-dependent BER pathway (By similarity). Plays a role in reversing blocked 3' DNA ends, problematic lesions that preclude DNA synthesis (By similarity). Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes (PubMed:18025127, PubMed:19556307). Required for proper cell cycle progression during proliferation of peripheral lymphocytes (PubMed:15319281).|||Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends.|||Interacts with PCNA (PubMed:12573260). This interaction is increased by misincorporation of uracil in nuclear DNA (By similarity).|||Mice show abnormalities in proliferating haemopoietic organs, such as dyshematopoiesis, defect in lymphopoiesis, and delayed S-phase and G2/M-phase arrest.|||Mitochondrion|||Nucleus|||Probably binds two magnesium or manganese ions per subunit.|||The PCNA interacting protein (PIP) box mediates interaction with PCNA and recruitment to DNA single-strand breaks.|||Up-regulated in both the nucleus and the cytosol of B cells stimulated to switch. http://togogenome.org/gene/10090:Or6a2 ^@ http://purl.uniprot.org/uniprot/Q9QWU6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tgfb1i1 ^@ http://purl.uniprot.org/uniprot/Q62219 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paxillin family.|||First detected in the developing heart tube at 8.0 dpc and then in cardiac, skeletal and smooth muscle during early stages of development. Highly expressed in differentiating gut epithelial cells.|||Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity.|||Homooligomer (PubMed:16737959). Interacts with PPARG (PubMed:15687259). Interacts with TRAF4 (By similarity). Interacts with CRIP2 (PubMed:15713747). Interacts with HSPB1 (PubMed:11546764). Interacts with ILK (PubMed:16737959). Interacts with LIMS1 and LIMS2 (PubMed:16737959). Interacts with NCK2 (PubMed:10330411). Interacts with NUDT16L1 (PubMed:11805099). Interacts with PAK (PubMed:10330411). Interacts with PTPN12 (PubMed:10092676). Interacts with TCF3 (PubMed:16291758). Interacts with TCF7L2 (PubMed:16291758). Interacts with VCL (PubMed:9858471). Interacts (via LD motif 3) with GIT1 (PubMed:12153727). Also interacts with GIT2 (PubMed:10330411). Forms a complex with ARHGEF7 (PubMed:10330411, PubMed:12153727). Interacts with AR/androgen receptor in a ligand-dependent manner (PubMed:11779876). Interacts with CSK (PubMed:9858471, PubMed:17233630). Interacts with PTK2/FAK1 and PTK2B/PYK2 (PubMed:9422762, PubMed:9756887, PubMed:10330411, PubMed:9858471, PubMed:10649439). Interacts with SLC6A3 (PubMed:12177201). Interacts with SLC6A4 (By similarity). Interacts with NR3C1 (PubMed:10848625). Interacts with SMAD3 (PubMed:14755691). Interacts with MAPK15 (PubMed:16624805). Interacts with SRC (By similarity). Interacts with LYN (By similarity). Interacts with talin (By similarity). Interacts (via LIM zinc-binding domain 2) with CBLC (via RING-type zinc finger); the interaction is direct and enhances CBLC E3 ubiquitin-protein ligase activity (By similarity). Interacts with PARVA (PubMed:11134073). Interacts with PXN (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus matrix|||Phosphorylated by gonadotropin-releasing hormone-activated SRC.|||The LD (leucine and aspartate-rich) motif 3 mediates interaction with GIT1 and functions as a nuclear export signal.|||The LIM zinc-binding domains mediate glucocorticoid receptor coactivation and interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG, TCF3, TCF7L2, SLC6A3 and SMAD3. The LIM zinc-binding 2 and LIM zinc-binding 3 domains mediate targeting to focal adhesions and actin stress fibers. The LIM zinc-binding 3 and LIM zinc-binding 4 domains mediate interaction with TRAF4 and MAPK15. The LIM zinc-binding 4 domain mediates interaction with HSPB1, homooligomerization and targeting to the nuclear matrix. The LIM zinc-binding 3 domain mediates interaction with PTPN12.|||Transcripts of the alpha group are more abundantly expressed.|||Transcripts of the alpha group are more abundantly expressed. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Ubiquitously expressed. Higher expression is detected in lung and spleen. Expression decreases during pregnancy in mammary glands. Expressed in all brain areas, with higher levels in cerebellum, prefrontal cortex and hypothalamus. Expressed in smooth muscle, myoepithelial cells and platelets (at protein level). Preferentially expressed in mesenchymal versus epithelial cells (at protein level).|||Up-regulated during epithelial to mesenchymal transformation. Up-regulated by TGFB1 and hydrogen peroxide.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Rhox4f ^@ http://purl.uniprot.org/uniprot/Q2MDF8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Tcaf1 ^@ http://purl.uniprot.org/uniprot/Q8BNE1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCAF family.|||Cell membrane|||Interacts with TRPM8 (via N-terminus and C-terminus domains); the interaction inhibits TRPM8 channel activity. Interacts with TRPV6.|||Positively regulates the plasma membrane cation channel TRPM8 activity. Involved in the recruitment of TRPM8 to the cell surface. Promotes prostate cancer cell migration inhibition in a TRPM8-dependent manner.|||The C-terminal region is necessary for the channel activity stimulation. http://togogenome.org/gene/10090:Ndufb10 ^@ http://purl.uniprot.org/uniprot/Q9DCS9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. Complex I has an NADH dehydrogenase activity with ubiquinone as an immediate electron acceptor and mediates the transfer of electrons from NADH to the respiratory chain.|||Belongs to the complex I NDUFB10 subunit family.|||Complex I is composed of 45 different subunits. Interacts with CHCHD4.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:H2ac18 ^@ http://purl.uniprot.org/uniprot/B2RWH3|||http://purl.uniprot.org/uniprot/Q6GSS7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Ergic3 ^@ http://purl.uniprot.org/uniprot/Q9CQE7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ERGIC family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Expression is particularly strong in liver, kidney and brain but is almost undetectable in heart.|||Forms homodimers (By similarity). May form a heteromeric complex composed of ERGIC1, ERGIC2 and ERGIC3 (By similarity). Within the complex, the interaction with ERGIC1 is direct (By similarity). Interacts with ERGIC1/ERGIC32 (By similarity). Interacts with ERGIC2, the interaction is required for the stable expression of both proteins (By similarity). Interacts with MARCHF2 (By similarity). Interacts with SERPINA1/alpha1-antitrypsin and HP/haptoglobin (By similarity).|||Possible role in transport between endoplasmic reticulum and Golgi. Positively regulates trafficking of the secretory proteins alpha1-antitrypsin/SERPINA1 and HP/haptoglobin (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Katnal2 ^@ http://purl.uniprot.org/uniprot/Q9D3R6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily. A-like 2 sub-subfamily.|||Cytoplasm|||Severs microtubules in vitro in an ATP-dependent manner. This activity may promote rapid reorganization of cellular microtubule arrays.|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Kif26a ^@ http://purl.uniprot.org/uniprot/Q52KG5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical kinesin that plays a key role in enteric neuron development. Acts by repressing a cell growth signaling pathway in the enteric nervous system development, possibly via its interaction with GRB2 that prevents GRB2-binding to SHC, thereby attenating the GDNF-Ret signaling. Binds to microtubules but lacks microtubule-based motility due to the absence of ATPase activity (PubMed:19914172). Plays a critical role in cerebral cortical development. It probably acts as a microtubule stabilizer that regulates neurite growth and radial migration of cortical excitatory neurons (PubMed:36228617).|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIF26 subfamily.|||Expressed in several neuronal populations.|||In contrast to other kinesin-like proteins, residues required for ATPase activity are missing.|||Interacts with GRB2 (via SH2 domain).|||Mice exhibit growth retardation, become emaciated, and die within 5 weeks of birth. The median and mean life span is 15 and 16 days. Macroscopic dissection reveal that mice suffered from megacolon, with dilation from the distal small intestine to the proximal colon and display enteric nerve hyperplasia. Severe occlusion are observed in the distal colon, because the colon motility is not coordinated. Defects are due to abnormal enteric nervous system (ENS) proliferation.|||Strong expression is detected in substantia nigra in brain and enteric nervous system in colon at P12. In colon sections at 12.5 dpc, 14.5 dpc, and P12, it is exclusively expressed in enteric nervous system (ENS). Also detected in dorsal root ganglion and spinal cord gray matter at 14.5 dpc.|||cytoskeleton http://togogenome.org/gene/10090:Krtap22-2 ^@ http://purl.uniprot.org/uniprot/J3QNX6 ^@ Function|||Subunit ^@ In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:H2-M9 ^@ http://purl.uniprot.org/uniprot/O19442 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Or4c12 ^@ http://purl.uniprot.org/uniprot/Q8VEZ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Crybg2 ^@ http://purl.uniprot.org/uniprot/A0A2I3BQG2|||http://purl.uniprot.org/uniprot/B7ZCC2 ^@ Similarity ^@ Belongs to the beta/gamma-crystallin family. http://togogenome.org/gene/10090:Msln ^@ http://purl.uniprot.org/uniprot/Q61468 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mesothelin family.|||By WNT1 but not by WNT5A in mammary epithelial cells.|||Cell membrane|||Expressed at 7 dpc, down-regulated at 11 dpc, re-expressed at 15 dpc and peaks at 17 dpc. Present in embryonic diaphragm (at protein level).|||Golgi apparatus|||Highly expressed in lung and heart. Expressed at low levels in spleen, liver, kidney and testis. Present in lung (at protein level).|||Interacts with MUC16.|||Megakaryocyte-potentiating factor (MPF) may potentiate megakaryocyte colony formation.|||Membrane-anchored forms may play a role in cellular adhesion.|||Mice have normal growth and reproductive function, and normal platelet counts.|||Proteolytically cleaved by a furin-like convertase to generate megakaryocyte-potentiating factor (MPF), and the cleaved form of mesothelin.|||Secreted http://togogenome.org/gene/10090:Fkbp15 ^@ http://purl.uniprot.org/uniprot/Q6P9Q6 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FKBP-type PPIase family.|||Cytoplasm|||Early endosome|||Expressed in brain, with highest levels in the granular cell layer of cerebellum and in the granule cell layer of dentate gyrus.|||Interacts with WIP and actin (By similarity). Interacts with TBC1D23 (PubMed:29084197).|||Involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement (By similarity). May be involved in the cytoskeletal organization of neuronal growth cones. Seems to be inactive as a PPIase.|||Strongly expressed in the developing nervous system at 18.5 dpc. Present in brain, heart, lung, kidney and thymus at 18.5 dpc (at protein level).|||The PPIase FKBP-type domain seems to be inactive both for FK506-binding and enzymatic activity.|||The central coiled-coil region is responsible for association with early endosomes.|||axon http://togogenome.org/gene/10090:Syce1l ^@ http://purl.uniprot.org/uniprot/Q5D525 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the SYCE family.|||Isoform 1 is abundantly expressed in testis and weakly in ovary, it is not found in other tissues. Isoform 2 is expressed in testis and poorly in brain, heart, lung and other examined tissues.|||May be involved in meiosis. Isoform 1 may be involved in meiosis during spermatogenesis while isoform 2 is probably related to a later stage of meiosis, in the development stage of secondary spermatocytes and spermatids.|||Not detected in embryo. Isoform 1 is detected in testis at day 8 after birth while isoform 2 at day 17. http://togogenome.org/gene/10090:Slc15a4 ^@ http://purl.uniprot.org/uniprot/Q91W98 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.|||Early endosome membrane|||Endosome membrane|||Interacts with TASL; leading to TASL recruitment to endolysosome.|||Lysosome membrane|||Mice are fertile and look healthy but display impaired cytokine production in dendritic cells (PubMed:21277849). Reduced uptake of L-histidine in brain (PubMed:27845049).|||Preferentially expressed in immune tissues, including B-cells and dendritic cells (PubMed:21277849). Highly expressed in macrophages (PubMed:29784761).|||Proton-coupled amino-acid transporter that mediates the transmembrane transport of L-histidine and some di- and tripeptides from inside the lysosome to the cytosol, and plays a key role in innate immune response (PubMed:19570976, PubMed:21277849, PubMed:25238095, PubMed:27845049, PubMed:29305823). Able to transport a variety of di- and tripeptides, including carnosine and some peptidoglycans (PubMed:29784761). Transporter activity is pH-dependent and maximized in the acidic lysosomal environment (By similarity). Involved in the detection of microbial pathogens by toll-like receptors (TLRs) and NOD-like receptors (NLRs), probably by mediating transport of bacterial peptidoglycans across the endolysosomal membrane: catalyzes the transport of certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand, and L-alanyl-gamma-D-glutamyl-meso-2,6-diaminoheptanedioate (tri-DAP), the NOD1 ligand (PubMed:19570976, PubMed:23028315, PubMed:25238095, PubMed:24695226, PubMed:29784761). Required for TLR7, TLR8 and TLR9-mediated type I interferon (IFN-I) productions in plasmacytoid dendritic cells (pDCs) (PubMed:21045126, PubMed:23382217, PubMed:25238095, PubMed:30262916). Independently of its transporter activity, also promotes the recruitment of innate immune adapter TASL to endolysosome downstream of TLR7, TLR8 and TLR9: TASL recruitment leads to the specific recruitment and activation of IRF5 (By similarity). Required for isotype class switch recombination to IgG2c isotype in response to TLR9 stimulation (PubMed:25310967). Required for mast cell secretory-granule homeostasis by limiting mast cell functions and inflammatory responses (PubMed:29155995). http://togogenome.org/gene/10090:Parvg ^@ http://purl.uniprot.org/uniprot/E9PYG5|||http://purl.uniprot.org/uniprot/Q8CEF2|||http://purl.uniprot.org/uniprot/Q9ERD8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the parvin family.|||Cell membrane|||Expressed strongly in spleen and testis, moderately in lung and weakly in brain and heart.|||Interacts with integrin-linked protein kinase and actin.|||Membrane|||Probably plays a role in the regulation of cell adhesion and cytoskeleton organization.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Cadps ^@ http://purl.uniprot.org/uniprot/Q80TJ1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates catecholamine loading of DCVs. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles by acting as a PtdIns(4,5)P2-binding protein that acts at prefusion step following ATP-dependent priming and participates in DCVs-membrane fusion. However, it may also participate in small clear synaptic vesicles (SVs) exocytosis and it is unclear whether its function is related to Ca(2+) triggering (By similarity).|||During brain development, its expression is similar to that of synaptic markers. Expression is first detectable late in embryogenesis (14 dpc) and increases to reach a plateau about 20 days after birth, when most synapses have been formed (at protein level).|||Homodimer. Interacts with the dopamine receptor DRD2 (By similarity). Interacts with RASL10B.|||In the heart, up-regulated by hypertrophic stimuli.|||Mice die within 30 minutes after birth but do not display obvious developmental or biochemical abnormalities. They show a strong reduction in the frequency of amperometrically detectable release events of transmitter-filled vesicles, while the total number of fusing vesicles, as judged by capacitance recordings or total internal reflection microscopy, remains unchanged.|||Present in brain and adrenal glands (at protein level). Specifically expressed in neural and endocrine secretory tissues. Strongly expressed in almost all nerve cells of the brain, although it is absent from glial cells. Expressed in the cardiac atria, but not ventricles.|||Synapse|||The PH domain is essential for regulated exocytosis and binds phospholipids and plasma membrane. It however does not mediate binding to DCVs (By similarity).|||The sequence differs from that shown due to a duplication of 90 bp after position 107.|||neuronal dense core vesicle membrane http://togogenome.org/gene/10090:Slc26a6 ^@ http://purl.uniprot.org/uniprot/Q8CIW6 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Apical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Functions in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride-formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Its association with carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence maximizes the local concentration of bicarbonate at the transporter site. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride-oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH.|||Apical membrane chloride-bicarbonate exchange activity of the pancreatic duct is inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Oxalate secretion in the duodenum and chloride-formate exchange activity is inhibited by DIDS.|||Cell membrane|||Chloride-formate exchange activity and transcellular sulfate absorption is inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS).|||Cytoplasmic vesicle membrane|||Expressed in kidney (at protein level). Expressed in spermatogenic cells. Expressed in intestine, kidney, testis, brain, muscle, heart, and stomach. Expressed in the submandibular and sublingual salivary glands.|||Expressed in the heart.|||Highly expressed in stomach, kidney, heart and small intestine, low in the lung, liver, testis, brain, skeletal muscle and colon.|||Interacts (via C-terminal domain) with PDZK1 (via C-terminal PDZ domain); the interaction induces chloride and oxalate exchange transport (PubMed:16141316). Interacts with CFTR, SLC26A3 and NHERF1 (PubMed:21976599). Interacts with AHCYL1; the interaction increases SLC26A6 activity (PubMed:23542070).|||Mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2 (PubMed:12217875, PubMed:23933580). Also mediates exchange of chloride-formate and chloride-oxalate ions (PubMed:11459928, PubMed:12217875, PubMed:15203903, PubMed:17151144, PubMed:23933580). Mediates transcellular sulfate absorption (PubMed:12217875).|||Mice show an important decrease in salt absorption in the intestine and failed to develop hypertension on a high-fructose diet. Show a reduction in pancreatic duct fluid and bicarbonate secretion. Show enhanced oxalate absorption in the intestine leading to hyperoxalemia and hyperoxaluria with high incidence of calcium-oxalate stones formation.|||Microsome|||N-glycosylated (PubMed:27681177). Glycosylation at Asn-174 positively regulates its chloride oxalate exchanger activity (By similarity).|||Up-regulated by dietary fructose intake (at protein level). http://togogenome.org/gene/10090:Commd1 ^@ http://purl.uniprot.org/uniprot/Q8K4M5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Endosome membrane|||Monomer, homodimer. Can form heterodimers with other COMM domain-containing proteins but only certain combinations may exist in vivo. Interacts (via COMM domain) with COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 (via COMM domain). Identified in a complex with an E3 ubiquitin ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1; in the complex interacts directly with SOCS1 and CUL2. Interacts directly with ATP7B (via the N-terminal region). Interacts with CCS, CDKN2A, RELA, REL, RELB, NFKB1/p105, NFKB2/p100, NFKBIB, SCNN1D, SCNN1B, CFTR, CLU, SGK1, AKT1, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, HIF1A. Identified in a complex with NF-kappa-B. Interacts directly with SLC12A2. Interacts with CCDC22 and CCDC93; proposed to be a component of the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22, CCDC93. Interacts with VPS35L; the interaction associates CCC complex with retriever complex. Interacts with ATP7A. Interacts with FAM107A; this interaction stabilizes COMMD1 in the nucleus.|||Nucleus|||Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2. Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity. Involved in the regulation of membrane expression and ubiquitination of SLC12A2. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes. Promotes CFTR cell surface expression through regulation of its ubiquitination. Down-regulates SOD1 activity by interfering with its homodimerization. Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes. Can bind one copper ion per monomer. May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1. Negatively regulates neuroblastoma G1/S phase cell cycle progression and cell proliferation by stimulating ubiquitination of NF-kappa-B subunit RELA and NF-kappa-B degradation in a FAM107A- and actin-dependent manner.|||Recycling endosome|||Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Gpr153 ^@ http://purl.uniprot.org/uniprot/Q8K0Z9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Fjx1 ^@ http://purl.uniprot.org/uniprot/Q8BQB4 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an inhibitor of dendrite extension and branching.|||Belongs to the FJX1/FJ family.|||Expressed in brain, kidney and lung. In the telencephalon, expressed in the piriform cortex, hippocampus and olfactory bulb. In the diencephalon, expressed in the dorsal thalamus. Expressed in Purkinje cells of the cerebellum and in numerous medullary nuclei.|||Expressed in embryo at 8.5 dpc onward. In the neural plate, expressed in the presumptive forebrain and midbrain and in rhombomere at 4 and 8.5 dpc. Expressed in the limb buds and in the ectoderm of the first branchial arches at 9.5 dpc. In the brain, expressed in the dorsal mesencephalon (tectum) and prosencephalon (presumptive isocortex) at 9.5, 10.5 and 11.5 dpc. In the cortex, expressed in dorsolateral patch of the neuroepithelium at 10.5 dpc. Expressed in the ectoderm of the branchial arch and the oral ectoderm at 10.5 dpc. In the limbs, expressed in the apical ectodermal ridge at 11.5 dpc. Expressed in the telecephalon, ventricles, diencephalon and medulla oblongata at 12.5 dpc. Expressed in the neural tube, cochlear ganglion and olfactory bulb at 14.5 dpc. In the kidney, lung and intestine, expressed in epithelial cells at 14.5 dpc.|||Glycosylated.|||Knockout mice for this gene exhibited an increase in dendrite extension and branching of pyramidal neurons in the CA1 region of the hippocampus.|||Secreted|||Undergoes proteolytic cleavage.|||Up-regulated by Notch. http://togogenome.org/gene/10090:Slc17a4 ^@ http://purl.uniprot.org/uniprot/A0A2C9F2D4|||http://purl.uniprot.org/uniprot/Q5NCM1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions (PubMed:22460716). Mediates chloride-dependent transport of urate (PubMed:22460716). Mediates sodium-independent high affinity transport of thyroid hormones including L-thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3) (By similarity). Can actively transport inorganic phosphate into cells via Na(+) cotransport (By similarity).|||Apical cell membrane|||Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.|||Expressed in the small intestine (at protein level).|||Membrane http://togogenome.org/gene/10090:Ppm1g ^@ http://purl.uniprot.org/uniprot/Q61074 ^@ Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||By FGF-4 and serum.|||Highly expressed in testis. Low level of expression in kidney. Also expressed in a number of tissues undergoing proliferation including embryo, uterus at pregnancy, placenta, and ovaries.|||Interacts with NOL3; may dephosphorylate NOL3.|||May be involved in regulation of cell cycle.|||Membrane|||Nucleus http://togogenome.org/gene/10090:Poli ^@ http://purl.uniprot.org/uniprot/Q6R3M4 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-Y family.|||Binds nucleotide much more tightly and catalyzes nucleotide insertion much more efficiently in the presence of Mg(2+) than in the presence of Mn(2+).|||Detected in testis, and at very low levels in spleen, lung and brain. Detected in round spermatids, but not in prophase spermatocytes.|||Error-prone DNA polymerase specifically involved in DNA repair (PubMed:15026325, PubMed:16357261). Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls (PubMed:15026325, PubMed:16357261). Favors Hoogsteen base-pairing in the active site. Inserts the correct base with high-fidelity opposite an adenosine template (By similarity). Exhibits low fidelity and efficiency opposite a thymidine template, where it will preferentially insert guanosine (By similarity). May play a role in hypermutation of immunoglobulin genes (By similarity). Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but may not have lyase activity (By similarity).|||Interacts with POLH (By similarity). Interacts with REV1 (PubMed:14657033). Interacts with ubiquitin (PubMed:16357261).|||Monoubiquitinated (PubMed:16357261). Protein monoubiquitination prevents POLI binding to ubiquitin via the ubiquitin-binding motif 1 and ubiquitin-binding motif 2 (PubMed:16357261).|||Nucleus|||The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity.|||Ubiquitin-binding motif 1 and ubiquitin-binding motif 2 regulate POLI protein monoubiquitination and localization to nuclear foci after UV-induced DNA damage. http://togogenome.org/gene/10090:Dalrd3 ^@ http://purl.uniprot.org/uniprot/Q6PJN8 ^@ Function|||Subunit ^@ Involved in tRNA methylation. Facilitates the recognition and targeting of tRNA(Arg)(CCU) and tRNA(Arg)(UCU) substrates for N(3)-methylcytidine modification by METTL2.|||Part of a complex containing tRNA(Arg) and METTL2. Interacts with tRNA(Arg)(CCU) and tRNA(Arg)(UCU). Interacts with METTL2. http://togogenome.org/gene/10090:Zp2 ^@ http://purl.uniprot.org/uniprot/P20239 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZP domain family. ZPA subfamily.|||Can form homopolymers that assemble into long fibers (in vitro) (PubMed:17559063). Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers (PubMed:3845123). Interacts with ZP3 (By similarity).|||Cell membrane|||Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP2 may act as a secondary sperm receptor.|||Expressed during the 2-week growth phase of oogenesis, prior to ovulation.|||Expressed in oocytes (at protein level).|||N-glycosylated.|||O-glycosylated; contains sulfate-substituted glycans.|||Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida.|||Proteolytically cleaved in the N-terminal part by the metalloendopeptidase ASTL exocytosed from cortical granules after fertilization, yielding a N-terminal peptide of about 30 kDa which remains covalently attached to the C-terminal peptide via disulfide bond(s). This cleavage may play an important role in the post-fertilization block to polyspermy. Additional proteolytically cleavage of the N-terminal peptide of 30 kDa occurs in one-cell and two-cell embryos.|||The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.|||Zona pellucida http://togogenome.org/gene/10090:Gm1110 ^@ http://purl.uniprot.org/uniprot/F6Y113 ^@ Similarity ^@ Belongs to the glycosyl hydrolase 35 family. http://togogenome.org/gene/10090:Kcnh8 ^@ http://purl.uniprot.org/uniprot/F6TUN6|||http://purl.uniprot.org/uniprot/P59111 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.1/KCNH8 sub-subfamily.|||Membrane|||Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, outward rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly (By similarity).|||The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||There seems to be a problem in the assembly of the Mouse genome in the region covered by contigs AC125051 and AC131674. http://togogenome.org/gene/10090:Kcne2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1J2|||http://purl.uniprot.org/uniprot/Q9D808 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Associated with KCNH2/HERG is proposed to form the rapidly activating component of the delayed rectifying potassium current in heart (IKr). May associate with KCNQ2 and/or KCNQ3 and modulate the native M-type current. May associate with HCN1 and HCN2 and increase potassium current (By similarity). Interacts with KCNQ1; forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (By similarity). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability.|||Apical cell membrane|||Belongs to the potassium channel KCNE family.|||Cell membrane|||Interacts with KCNB1. Associates with KCNH2/ERG1. May associate with KCNQ2 and KCNQ3. Associates with HCN1 and probably HCN2. Heteromultimer with KCNC2. Interacts with KCNC2 (By similarity). Interacts with KCNQ1 (PubMed:24595108). Forms a heterooligomer complex with KCNQ1 that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (By similarity).|||Mutant mice show increased pentylenetetrazole-induced seizure susceptibility and mortality associated with a reduction of myo-inositol concentration in cerebrospinal fluid. http://togogenome.org/gene/10090:Fzd5 ^@ http://purl.uniprot.org/uniprot/Q9EQD0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Binding of unsaturated fatty acid molecules (via FZ domain) promotes homodimerization (via FZ domain). Interacts with WNT2B (By similarity). Interacts with WNT7A (PubMed:18230341, PubMed:20530549). Interacts with GOPC (PubMed:11520064).|||Cell membrane|||Detected at low levels in neonate brain; expression levels increase steadily during the first four weeks after birth and show a further increase in adults (at protein level) (PubMed:20530549). Expressed in the yolk sac, placenta, eye and lung bud at 9.5 dpc. At 10.5 dpc, also expressed in the placental blood vessel of embryonic origin (PubMed:11092808).|||Detected in hippocampus (at protein level) (PubMed:20530549). Expressed in eye, kidney, lung, chondrocytes, epithelial cells of the small intestine and gobelet cells of the colon (PubMed:8626800).|||Full embryonic lethality around 12.5 dpc, due to defects in yolk sac and placenta vascularization.|||Golgi apparatus membrane|||Perikaryon|||Receptor for Wnt proteins (PubMed:11092808, PubMed:18230341). Can activate WNT2, WNT10B, WNT5A, but not WNT2B or WNT4 (in vitro); the in vivo situation may be different since not all of these are known to be coexpressed (PubMed:11092808). In neurons, activation of WNT7A promotes formation of synapses (By similarity). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:18230341). The canonical Wnt/beta-catenin signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (PubMed:18230341). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (Probable). Plays a role in yolk sac angiogenesis and in placental vascularization (PubMed:11092808).|||Synapse|||The FZ domain is involved in binding with Wnt ligands.|||The PDZ-binding motif mediates interaction with GOPC.|||Ubiquitinated by RNF43 and ZNRF3, leading to its degradation by the proteasome.|||axon|||dendrite http://togogenome.org/gene/10090:Syna ^@ http://purl.uniprot.org/uniprot/Q5G5D5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gamma type-C retroviral envelope protein family.|||Cell membrane|||Embryonic lethal with no survival beyond stage 14.5 dpc (PubMed:19564597). Embryos show retarded growth but otherwise have no significant morphological defects (PubMed:19564597). Placental development is abnormal with significantly reduced vascularization of extraembryonic tissues (PubMed:19564597). In the placental labyrinth, there is an expansion of trophoblast cells which reduces available space for fetal blood vessels (PubMed:19564597). Trophoblast cells fail to fuse and form syncytiotrophoblast layer I (SynT-I), however development of syncytiotrophoblast layer II (SynT-II) is not significantly affected (PubMed:19564597). Double knockouts of Syna and Synb are embryonic lethal at stage 9.5 dpc to 10.5 dpc, indicating a more severe phenotype than the Syna single knockout (PubMed:22032925).|||Expressed in the placental labyrinth from stage 8.5 dpc onwards.|||Highly expressed in placenta where it localizes to syncytiotrophoblasts of the labyrinthine zona (PubMed:15644441). Specifically localizes to syncytiotrophoblast layer I (SynT-I) (PubMed:18448564). Also detected at very low levels in hippocampus, brain, testis and ovary (PubMed:15644441).|||Synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R.|||The CXXC motif is highly conserved across a broad range of retroviral envelope proteins. It is thought to participate in the formation of a labile disulfide bond possibly with the CX6CC motif present in the transmembrane protein. Isomerization of the intersubunit disulfide bond to an SU intrachain disulfide bond is thought to occur upon receptor recognition in order to allow membrane fusion.|||The mature protein consists of a trimer of SU-TM heterodimers (Probable). The SU-TM heterodimers are attached by a labile interchain disulfide bond (By similarity).|||The mouse genome contains a high percentage of proviral-like elements, also called endogenous retroviruses (ERVs) that are the genomic traces of ancient infections of the germline by exogenous retroviruses. Although most of these elements are defective, some have conserved a functional envelope (env) gene, most probably diverted by the host for its benefit.|||This endogenous retroviral envelope protein has retained its original fusogenic properties (PubMed:15644441, PubMed:17762178, PubMed:18077339, PubMed:19564597, PubMed:27589388). Together with Synb, participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis (PubMed:19564597). Syna is essential for placental development and is specifically required for formation of syncytiotrophoblast layer I (SynT-I) (PubMed:19564597). Promotes muscle myoblast fusion (PubMed:27589388). Does not have immunosuppressive activity (PubMed:18077339). http://togogenome.org/gene/10090:Mtmr11 ^@ http://purl.uniprot.org/uniprot/Q3V1L6 ^@ Caution|||Similarity ^@ Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 380 in the dsPTPase catalytic loop, suggesting that it has no phosphatase activity.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily. http://togogenome.org/gene/10090:Rasgrp3 ^@ http://purl.uniprot.org/uniprot/Q6NZH9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the RASGRP family.|||cytosol http://togogenome.org/gene/10090:Galc ^@ http://purl.uniprot.org/uniprot/P54818 ^@ Caution|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 59 family.|||Defects in Galc are the cause of the 'twitcher' phenotype; an autosomal recessive leukodystrophy similar to the human disease (Krabbe disease). This deficiency results in the insufficient catabolism of several galactolipids that are important in the production of normal myelin.|||Detected in brain and kidney.|||Hydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine (PubMed:8769874, PubMed:10861297). Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon (By similarity).|||It is uncertain whether Met-1 or Met-17 is the initiator.|||Lysosome http://togogenome.org/gene/10090:Uba6 ^@ http://purl.uniprot.org/uniprot/Q8C7R4 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34 (By similarity). Essential for embryonic development. Required for UBD/FAT10 conjugation.|||Belongs to the ubiquitin-activating E1 family.|||Embryonic lethality at early stage.|||Forms a thioester with UBD in cells stimulated with tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg) (PubMed:17889673). http://togogenome.org/gene/10090:Atp11c ^@ http://purl.uniprot.org/uniprot/E9QKK8|||http://purl.uniprot.org/uniprot/Q9QZW0 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane (PubMed:24904167, PubMed:26799398, PubMed:30018401, PubMed:24898253). Major PS-flippase in immune cell subsets (PubMed:30018401). In erythrocyte plasma membrane, it is required to maintain PS in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for erythrocyte clearance by splenic macrophages (PubMed:24898253). Required for B cell differentiation past the pro-B cell stage (PubMed:21423173). Seems to mediate PS flipping in pro-B cells (PubMed:21423172, PubMed:26799398). May be involved in the transport of cholestatic bile acids (PubMed:21518881).|||Cell membrane|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP11C and an accessory beta subunit TMEM30A.|||Early endosome membrane|||Endoplasmic reticulum membrane|||Membrane|||Mice defective in Atp11c show defective B lymphopoiesis, specifically in mature bone marrow, pronounced stomatocytosis associated with anemia, hyperbilirubinemia linked to mild cholestasis and hepatocellular carcinoma.|||Phosphorylated at Ser-1113 likely by PRKCA; this creates a functional di-leucine motif that is sufficient for endocytosis.|||Proteolytically cleaved by CASP3, CASP6 and CASP7.|||Recycling endosome membrane|||The di-leucine motif is required for sorting to clathrin-coated endosomes upon ca(2+)-dependent PRKCA activation.|||Widely expressed. Expressed in retina, brain, liver and testes (at protein level) (PubMed:30018401). Expressed in lung, bone marrow, lymph nodes, prostate, ovary and uterus (PubMed:24904167). Expressed in fetus (PubMed:24904167). http://togogenome.org/gene/10090:Upf3b ^@ http://purl.uniprot.org/uniprot/Q3ULL6|||http://purl.uniprot.org/uniprot/Q80UI8 ^@ Similarity ^@ Belongs to the RENT3 family. http://togogenome.org/gene/10090:Ndel1 ^@ http://purl.uniprot.org/uniprot/Q9ERR1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nudE family.|||Expressed in brain, liver, lung and testis (at protein level). Expressed in brain, epididymis, eye, heart, kidney, large intestine, liver, ovary, pancreas, prostate, skeletal muscle, smooth muscle, spleen, submaxillary gland, testis, thymus and thyroid. Within the brain expression is pronounced in the cortex, hippocampus, olfactory bulb, striatum, thalamic and hypothalamic structures and in the molecular layer of the cerebellum. Largely excluded from cortical progenitor cells which express NDE1.|||Expression in the brain is detectable from 7 dpc, rises at 15 dpc and 17 dpc and peaks at P5. Enriched in the developing cortex, particularly in neuroblasts of the ventricular zone and postmitotic migrating cortical plate neurons. Interaction with DISC1 in the brain is developmentally regulated, peaking at 17 dpc and decreasing at P16 so as to be undetectable in the adult brain. Expressed in the testis from P12, when zygotene spermatocytes first appear, and expression subsequently rises at P27.|||Interacts with PLEKHM1 (via N- and C-terminus) (PubMed:27777970). Interacts with dynactin, PCM1 and PCNT. Interacts (via C-terminus) with CENPF (By similarity). Self-associates. Interacts with DISC1, dynein, tubulin gamma, KATNA1, KATNB1, microtubules, PAFAHB1 and YWHAE. Interacts directly with NEFL and indirectly with NEFH. Interacts with ZNF365 (By similarity).|||Palmitoylation at Cys-273 reduces affinity for dynein.|||Phosphorylated by CDK1 and MAPK1 (By similarity). Phosphorylated in mitosis. Phosphorylated by CDK5. Phosphorylation by CDK5 promotes interaction with KATNA1 and YWHAE.|||Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (PubMed:27777970).|||centrosome|||cytoskeleton|||kinetochore|||spindle http://togogenome.org/gene/10090:Or6c207 ^@ http://purl.uniprot.org/uniprot/Q8VFH3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gfm2 ^@ http://purl.uniprot.org/uniprot/E9Q7N5|||http://purl.uniprot.org/uniprot/Q3TSU6|||http://purl.uniprot.org/uniprot/Q8R2Q4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.|||Mitochondrial GTPase that mediates the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with MRRF. GTP hydrolysis follows the ribosome disassembly and probably occurs on the ribosome large subunit. Not involved in the GTP-dependent ribosomal translocation step during translation elongation.|||Mitochondrion|||This protein may be expected to contain an N-terminal transit peptide but none has been predicted. http://togogenome.org/gene/10090:Fbxo16 ^@ http://purl.uniprot.org/uniprot/Q9QZM9 ^@ Function|||Subunit ^@ Part of a SCF (SKP1-cullin-F-box) protein ligase complex.|||Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation. http://togogenome.org/gene/10090:Gpr87 ^@ http://purl.uniprot.org/uniprot/Q99MT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed at high levels in testis and brain and to a lesser extent placenta, ovary, prostate, and skeletal muscle but not in heart, lung, kidney, liver or intestine.|||Receptor for lysophosphatidic acid (LPA). Necessary for p53/TP53-dependent survival in response to DNA damage (By similarity). http://togogenome.org/gene/10090:Arfgef3 ^@ http://purl.uniprot.org/uniprot/Q3UGY8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in pancreatic islet (insulin granules of islet alpha and beta cells) and brain (at protein level).|||Interacts with PHB2 (By similarity).|||Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (PubMed:24711543). Also regulates glucagon granule production in pancreatic alpha cells (PubMed:25737957). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (By similarity).|||Viable and fertile with normal body weight gain. Mice exhibit postprandial hyperinsulinemia and hyperglycemia, and impaired glucose tolerance. Three month old animals show severe insulin resistance in liver and muscle tissue, probably due to chronic insulin exposure.|||secretory vesicle|||secretory vesicle membrane http://togogenome.org/gene/10090:Hnrnpul2 ^@ http://purl.uniprot.org/uniprot/Q00PI9 ^@ Subcellular Location Annotation|||Subunit ^@ Binds to MLF1 and retains it in the nucleus.|||Nucleus http://togogenome.org/gene/10090:Kcna3 ^@ http://purl.uniprot.org/uniprot/P16390 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.3/KCNA3 sub-subfamily.|||Cell membrane|||Heterotetramer of potassium channel proteins. Binds PDZ domains of DLG4 (By similarity).|||Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.|||N-glycosylation promotes the cell surface expression.|||The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Gzf1 ^@ http://purl.uniprot.org/uniprot/Q4VBD9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 13.5-14.5 dpc, strong expression in ureteric buds (at protein level). Expression decreases in the kidney after birth (at protein level). Expressed in the eyes and limbs during development (at protein level).|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Expressed in several tissues, with highest levels in liver. Also expressed in embryos from 7 to 17 dpc.|||Interacts with NCL.|||Nucleus|||Transcriptional repressor that binds the GZF1 responsive element (GRE) (consensus: 5'-TGCGCN[TG][CA]TATA-3'). May be regulating VSX2/HOX10 expression.|||nucleolus http://togogenome.org/gene/10090:Hsdl2 ^@ http://purl.uniprot.org/uniprot/B1AX78|||http://purl.uniprot.org/uniprot/Q2TPA8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Has apparently no steroid dehydrogenase activity.|||Peroxisome|||Up-regulated by cholesterol-rich food.|||Widely expressed. http://togogenome.org/gene/10090:Pde4dip ^@ http://purl.uniprot.org/uniprot/Q80YT7 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes (By similarity).|||Golgi apparatus|||Interacts with PDE4D (By similarity). Isoform 2 interacts with MAPRE1 and MAPRE3. Isoform 2 forms a pericentrosomal complex with AKAP9, CDK5RAP2 and EB1/MAPRE1; within this complex, may mediate MAPRE1-binding to CDK5RAP2. Interaction with AKAP9 stabilizes both proteins. Isoform 2 interacts (via N-terminus) with CAMSAP2; this interaction is much stronger in the presence of AKAP9. In complex with AKAP9, Isoform 2 recruits CAMSAP2 to the Golgi apparatus. Isoform 2 interacts with unglycosylated LGALS3BP; this interaction may connect the pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) to promote microtubule assembly and acetylation (By similarity).|||Participates in microtubule dynamics, promoting microtubule assembly. Depending upon the cell context, may act at the level of the Golgi apparatus or that of the centrosome. In complex with AKAP9, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. In complex with AKAP9, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension from the centrosome to the cell periphery, a crucial process for directed cell migration, mitotic spindle orientation and cell-cycle progression.|||Residues 1-150 are involved in AKAP9-binding.|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Vmn1r258 ^@ http://purl.uniprot.org/uniprot/D3YTW8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rrbp1 ^@ http://purl.uniprot.org/uniprot/Q99PL5 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane.|||Endoplasmic reticulum membrane|||Widely expressed. http://togogenome.org/gene/10090:Rrp36 ^@ http://purl.uniprot.org/uniprot/A0A0R4J045|||http://purl.uniprot.org/uniprot/Q3UFY0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with 90S and pre-40S pre-ribosomal particles.|||Belongs to the RRP36 family.|||Component of the 90S pre-ribosome involved in the maturation of rRNAs. Required for early cleavages of the pre-RNAs in the 40S ribosomal subunit maturation pathway.|||Involved in the early processing steps of the pre-rRNA in the maturation pathway leading to the 18S rRNA.|||nucleolus http://togogenome.org/gene/10090:Kcnc3 ^@ http://purl.uniprot.org/uniprot/A0A140LIW8|||http://purl.uniprot.org/uniprot/Q63959 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. C (Shaw) (TC 1.A.1.2) subfamily. Kv3.3/KCNC3 sub-subfamily.|||Cell membrane|||Detected on Purkinje cells in the dentate, interposed and medial nucleus in cerebellum (PubMed:15217387, PubMed:18448641). Detected in brainstem (PubMed:18539595). Detected at calyces of Held in the auditory brain stem (at protein level) (PubMed:26997484). Isoform KV3.3B is highly enriched in the brain, particularly in the cerebellum, where its expression is confined to Purkinje cells and deep cerebellar nuclei. Isoform KV3.3A is not expressed in cerebellum.|||Expression begins in cerebellar Purkinje cells between postnatal day 8 (P8) and P10 and continues through adulthood.|||Homotetramer. Heterotetramer with KCNC1 (By similarity). Interacts (via C-terminus) with HAX1. Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1. Interaction with HAX1 modulates channel gating (PubMed:26997484).|||Membrane|||Mice lacking both Kcnc3 and Kcnc1 are born at the expected Mendelian rate, but the pups do not thrive and all die about 26 days after birth when kept together with other littermates. Their failure to thrive may be due to motor problems; mutant pups survive when fed separately, but 45 days after birth their body weight is only 50 to 60 % of that of wild-type (PubMed:11517255). They appear uncoordinated and display severe ataxia, myoclonus and spontaneous whole-body muscle jerks, but display no obvious alterations in brain morphology (PubMed:11517255, PubMed:15217387, PubMed:16923152). Mice lacking only Kcnc3 still display ataxic gait and decreased motor skill, but to a lesser degree than mice lacking both Kcnc3 and Kcnc1 (PubMed:16923152, PubMed:18448641). Purkinje cell-specific expression of Kcnc3 restores normal motor skills (PubMed:18448641). Mutant mice are also much more sensitive to ethanol and fall sideways at ethanol concentrations that have no effect on wild-type mice (PubMed:11517255). They display increased locomotor and exploratory activity (PubMed:11517255, PubMed:15217387). Mice lacking Kcnc3 or both Kcnc3 and Kcnc1 are resistant to the tremorogenic agent harmaline (PubMed:15217387).|||N-glycosylated.|||Perikaryon|||Presynaptic cell membrane|||Probable cloning artifact. Incorrect C-terminus.|||The C-terminal cytoplasmic tail contributes to the regulation of channel inactivation and to the interaction with HAX1 and the Arp2/3 complex.|||The cytoplasmic N-terminus mediates N-type inactivation.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:18539595, PubMed:26997484, PubMed:24218544). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells (PubMed:15217387, PubMed:18448641, PubMed:24218544). Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (PubMed:24218544). Required for normal motor function (PubMed:16923152, PubMed:18448641). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).|||axon|||cell cortex|||cytoskeleton|||dendrite|||dendritic spine membrane http://togogenome.org/gene/10090:Slco1c1 ^@ http://purl.uniprot.org/uniprot/Q9ERB5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Knockout mice present a general hypothyroidal state of the CNS, with reduced levels of both T3 and T4, and increased activity of the iodothyronine-deiodinase D2.|||Mediates the Na(+)-independent high affinity transport of thyroid hormones at the plasma membrane of brain capillary endothelial cells (PubMed:15166123, PubMed:24691440, PubMed:22294745). The transport activity of substrates L-thyroxine (T4) and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) is much greater than that of 3,3',5-triiodo-L-thyronine (T3) (PubMed:15166123). The prehormone, T4, is the major form in the circulating blood and is converted to the active form, T3, by the iodothyronine-deiodinase in peripheral organs (PubMed:15166123). T3 plays an essential role in brain development via binding to specific nuclear receptors (thyroid hormone receptor) (PubMed:15166123, PubMed:22294745). Also transports organic anions such as the conjugated steroid 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)) (PubMed:15166123). Transports T4 and estrone-3-sulfate in a pH-insensitive manner (By similarity). May serve as a drug efflux system at the blood brain barrier (By similarity).|||Widely expressed throughout the brain except in the cerebellum (PubMed:15166123). Not detected in kidney, heart, lung, skeletal muscle, spleen, liver, nor testis (PubMed:15166123). Highly expressed in cerebral microvessels throughout the brain and in the choroid plexus (at mRNA and protein level) (PubMed:15166123, PubMed:18687783, PubMed:22294745). http://togogenome.org/gene/10090:Rasl10a ^@ http://purl.uniprot.org/uniprot/Q8K5A4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Isoprenylation is essential for nucleolar localization, and the proliferation-inhibiting activity of RASL10A.|||Potent inhibitor of cellular proliferation.|||nucleolus http://togogenome.org/gene/10090:Lage3 ^@ http://purl.uniprot.org/uniprot/A0A158SIT5|||http://purl.uniprot.org/uniprot/Q9CR70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTAG/PCC1 family.|||Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.|||Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. LAGE3 functions as a dimerization module for the complex.|||Cytoplasm|||Mouse embryos display primary microcephaly characterized by significantly shorter cortex lengths, cortex-midbrain midline lengths and cortex widths. Mice do not show a renal phenotype.|||Nucleus http://togogenome.org/gene/10090:Or8j3 ^@ http://purl.uniprot.org/uniprot/Q7TR80 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Apool ^@ http://purl.uniprot.org/uniprot/B1AV14|||http://purl.uniprot.org/uniprot/Q78IK4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the apolipoprotein O/MICOS complex subunit Mic27 family.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Specifically binds to cardiolipin (in vitro) but not to the precursor lipid phosphatidylglycerol. Plays a crucial role in crista junction formation and mitochondrial function.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with MICOS10/MIC10, IMMT/MIC60 and APOO/MIC23/MIC26.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Rtn4rl2 ^@ http://purl.uniprot.org/uniprot/Q7M6Z0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 13.5 dpc, strongly expressed in PNS ganglia and developing heart, and weakly expressed in brain and spinal cord. By postnatal day 1, strongly expressed in dorsal root ganglia and in dorsal and gray matter areas of spinal cord. Expressed in various adult brain structures including the amygdala, cerebral cortex, cerebellum, hippocampus and olfactory bulb.|||Belongs to the Nogo receptor family.|||Cell membrane|||Cell surface receptor that plays a functionally redundant role in the inhibition of neurite outgrowth mediated by MAG (By similarity). Plays a functionally redundant role in postnatal brain development (PubMed:27339102). Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Does not seem to play a significant role in regulating axon regeneration in the adult central nervous system (PubMed:22406547). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG (PubMed:26335717). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200).|||Detected in brain (PubMed:22406547). Detected in hippocampus neurons (at protein level) (PubMed:22325200).|||Interaction with MAG is controversial, and may be indirect (Probable). Interacts with MAG. Does not interact with OMG and RTN4 (By similarity).|||Membrane raft|||N-glycosylated.|||No visible phenotype (PubMed:19367338). Mutant sensory neurons show no decrease of the inhibition of neurite outgrowth by MAG (PubMed:19367338). Compared to wild-type littermates, cultured hippocampus neurons from mutant mice display an increased number of excitatory synapses (PubMed:22325200). Likewise, mice lacking both Rtn4r and Rtn4rl2 display no visible phenotype (PubMed:19367338). Sensory neurons from mice lacking both Rtn4r and Rtn4rl2 show moderately decreased inhibition of neurite outgrowth by MAG (PubMed:19367338). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have no visible phenotype, are healthy and viable (PubMed:22406547, PubMed:22325200). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have normal brain size and grossly normal brain anatomy, but display disruption of medial brain structures, including an absence of the fasciola cinereum, corpus callosum agenesis and formation of bilateral Probst bundles indicative of the failure of callosally projecting neurons to extend across the midline (PubMed:27339102). Mice with a triple gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 display impaired ability to stay on a rotarod and increased spontaneous locomotion (PubMed:27339102). These mice display an increased number of excitatory synapses in the apical dendritic regions of hippocampus neurons, an increase in the complexity of dendrite structure and increased total dendrite length (PubMed:22325200). One month after birth, mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a significant reduction in the survival of motoneurons (PubMed:26335717). Compared to wild-type or single mutants, cerebellar granule cells from mice lacking Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated inhibition of neurite outgrowth, an inhibition that is strongly decreased on myelin deficient in Mag, Rtn4 and Omg (PubMed:22406547). Mice lacking both Rtn4r and Rtn4rl1 show increased axon regeneration after injury; the same effect is observed when Rtn4r, Rtn4rl1 and Rtn4rl2 are disrupted (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs further increases axon regeneration after injury (PubMed:22406547). Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 and combined disruption of Rtn4r and Rtn4rl2 have no effect on axon regeneration (PubMed:22406547).|||Perikaryon|||Undergoes zinc metalloproteinase-mediated ectodomain shedding in neuroblastoma cells; is released both as a full-length ectodomain and an N-terminal fragment containing the leucine-rich repeat (LRR) region of the protein.|||axon|||dendrite http://togogenome.org/gene/10090:Yy2 ^@ http://purl.uniprot.org/uniprot/Q3TTC2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the YY transcription factor family.|||Functions as a multifunctional transcription factor that may exhibit positive and negative control on a large number of genes. May antagonize YY1 and function in development and differentiation.|||Nucleus|||The gene encoding this protein appears to have arisen by retrotransposition of the YY1 gene in placental mammals. It is encoded by a single exon found in an intron of the gene Mbtps2.|||Weakly expressed by neuronal and glial cells in the cerebral cortex. Expressed by Purkinje cells and in the granular layers of the cerebellum. Expressed in all layers of spermatocytes in testis but not detected in sperm cells. http://togogenome.org/gene/10090:Rxfp3 ^@ http://purl.uniprot.org/uniprot/Q5Y988|||http://purl.uniprot.org/uniprot/Q8BGE9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for RNL3/relaxin-3. Binding of the ligand inhibit cAMP accumulation (By similarity). http://togogenome.org/gene/10090:Or2aj6 ^@ http://purl.uniprot.org/uniprot/G5E8J1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Clec4d ^@ http://purl.uniprot.org/uniprot/Q9Z2H6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of pathogen-associated molecular patterns (PAMPs) of bacteria and fungi. The PAMPs include alpha-mannans on C.albicans hypheas and mycobacterial trehalose 6,6'-dimycolate (TDM) (PubMed:23602766, PubMed:23911656). Interacts with signaling adapter Fc receptor gamma chain/FCER1G, likely via CLEC4E, to form a functional complex in myeloid cells (By similarity). Binding of mycobacterial TDM or C.albicans alpha-mannans to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes (PubMed:23602766, PubMed:23911656). The heterodimer formed with CLEC6A is active against fungal infection (By similarity). Functions as an endocytic receptor (By similarity). May be involved in antigen uptake at the site of infection, either for clearance of the antigen, or for processing and further presentation to T-cells (By similarity).|||Cell membrane|||Constitutively expressed in myeloid cells including dendritic cells (at protein level) (PubMed:23602766). Expressed in the macrophage populations of bone marrow, spleen, lung and lymph nodes (PubMed:9660840).|||Heterodimer with CLEC4E; disulfide-linked. CLEC4E acts as a bridge for interaction between CLEC4D and FCER1G to form a functional complex (By similarity). Heterodimer with CLEC6A; this heterodimer forms a pattern recognition receptor (PRR) against fungal infection (By similarity).|||Knockout mice are born at the expected Mendelian rate (PubMed:23602766). When compared to wild-type littermates, deficient mice show resistance to lethal systemic inflammation caused by exposure to mycobacterial cord factor/trehalose 6,6'-dimycolate (TDM) (PubMed:23602766). Mice are also susceptibility to C.albicans infections (PubMed:23911656). http://togogenome.org/gene/10090:Opa1 ^@ http://purl.uniprot.org/uniprot/H7BX01|||http://purl.uniprot.org/uniprot/P58281 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by guanine nucleotide exchange factor RCC1L.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.|||Cleavage at position S2 is mediated by YME1L (PubMed:24616225, PubMed:26785494). Cleavage may occur in the sequence motif Leu-Gln-Gln-Gln-Ile-Gln (LQQQIQ) (By similarity).|||Detected in brain (at protein level) (PubMed:11847212). Detected in brain, brain stem, heart, kidney, liver and skeletal muscle (PubMed:11847212).|||Dynamin-related GTPase that is essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission (PubMed:11847212, PubMed:24616225, PubMed:26785494, PubMed:28746876). Coexpression of isoform 1 with shorter alternative products is required for optimal activity in promoting mitochondrial fusion (By similarity). Binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation. The intrinsic GTPase activity is low, and is strongly increased by interaction with lipid membranes (By similarity). Plays a role in remodeling cristae and the release of cytochrome c during apoptosis (PubMed:16839884, PubMed:16839885). Proteolytic processing in response to intrinsic apoptotic signals may lead to disassembly of OPA1 oligomers and release of the caspase activator cytochrome C (CYCS) into the mitochondrial intermembrane space (PubMed:16839884, PubMed:16839885). Plays a role in mitochondrial genome maintenance (By similarity).|||Embryonic fibroblasts that lack Opa1 show a defect in apoptosis in response to intrinsic signals. This defect can be complemented by a soluble form of Opa1 targeted to the mitochondrial intermembrane space.|||Isoforms that contain the alternative exon 4b (present in isoform 2, but not in isoform 1) are required for mitochondrial genome maintenance, possibly by anchoring the mitochondrial nucleoids to the inner mitochondrial membrane.|||Membrane|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion membrane|||Oligomeric complex consisting of membrane-bound and soluble forms of OPA1 (PubMed:16839885). Interacts with CHCHD3 and IMMT; these interactions occur preferentially with soluble OPA1 forms (PubMed:21081504). Interacts with RCC1L; this interaction is direct (PubMed:28746876). Binds PARL (PubMed:16839884). Interacts with PRELID1 (By similarity).|||PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion (PubMed:20038678, PubMed:24550258, PubMed:22433842). Cleaved by OMA1 at position S1 following stress conditions (PubMed:20038678, PubMed:24550258, PubMed:22433842).|||Produced by cleavage at position S1 by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion. http://togogenome.org/gene/10090:Tmem14c ^@ http://purl.uniprot.org/uniprot/Q8C297|||http://purl.uniprot.org/uniprot/Q9CQN6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM14 family.|||Mitochondrion membrane|||Required for normal heme biosynthesis. http://togogenome.org/gene/10090:Sf3b5 ^@ http://purl.uniprot.org/uniprot/Q923D4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SF3B5 family.|||Component of the spliceosome B complex. Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42. SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Within the SF3B complex interacts directly with SF3B1 (via HEAT domain) and SF3B3. The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2. Component of the minor spliceosome, which splices U12-type introns (By similarity).|||Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex, a constituent of the spliceosome. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus http://togogenome.org/gene/10090:Creb5 ^@ http://purl.uniprot.org/uniprot/A0A0N4SUK5|||http://purl.uniprot.org/uniprot/A0A0N4SV71|||http://purl.uniprot.org/uniprot/Q8K1L0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family.|||Binds DNA as a homodimer or as a heterodimer with JUN or ATF2/CREBP1.|||Binds to the cAMP response element and activates transcription.|||Nucleus http://togogenome.org/gene/10090:Ssx9 ^@ http://purl.uniprot.org/uniprot/Q6XAS3 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:E130311K13Rik ^@ http://purl.uniprot.org/uniprot/Q8BN57 ^@ Function|||Subcellular Location Annotation ^@ May play a role in transcription regulation.|||Membrane http://togogenome.org/gene/10090:Btnl9 ^@ http://purl.uniprot.org/uniprot/Q8BJE2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Membrane http://togogenome.org/gene/10090:Tmem132e ^@ http://purl.uniprot.org/uniprot/Q6IEE6 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Artifactual sequence.|||Belongs to the TMEM132 family.|||Membrane|||Required for normal inner ear hair cell function and hearing.|||Widely expressed, with highest levels in the cochlea. In the cochlea, detected in spiral ganglion, the organ of Corti and stria vascularis. In the organ of Corti, prominently expressed in the outer and inner hair cells, especially at the apical and basal region of the outer hair cell body (at protein level). http://togogenome.org/gene/10090:Slco1a5 ^@ http://purl.uniprot.org/uniprot/A0A0G2JDD1|||http://purl.uniprot.org/uniprot/Q91YY5 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A conserved histidine residue in the third TMD (His-107) may play an essential role in the pH sensitivity of SLCO1A5/OATP1A5-mediated substrate transport.|||Basal cell membrane|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Expressed in brain, choroid plexus and lung, but not in liver or kidney.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), estrone 3-sulfate and prostaglandin E2, at the plasma membrane. Responsible for intestinal absorption of bile acids. Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (By similarity). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (PubMed:15255953). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (By similarity). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment. Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (By similarity). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity). http://togogenome.org/gene/10090:Pkp1 ^@ http://purl.uniprot.org/uniprot/P97350 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the beta-catenin family.|||Interacts (via N-terminus) with KRT5/CK5, KRT8/CK8 (via rod domain), KRT15/CK15 and KRT18/CK18 (via rod domain) as part of intermediate filaments (By similarity). Interacts with VIM (via rod domain) (By similarity). Interacts with DSP (By similarity). Interacts with DES (PubMed:10852826).|||Nucleus|||Seems to play a role in junctional plaques (By similarity). May facilitate the formation of intermediate filaments (By similarity). http://togogenome.org/gene/10090:Nsun4 ^@ http://purl.uniprot.org/uniprot/Q9CZ57 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.|||Embryonic lethal.|||Heterodimer with MTERFD2/MTERF4; this interaction seems to be required for NSUN4 recruitment to the mitochondrial large ribosomal subunit.|||Involved in mitochondrial ribosome assembly. 5-methylcytosine rRNA methyltransferase that probably is involved in mitochondrial ribosome small subunit (SSU) maturation by methylation of mitochondrial 12S rRNA at position 911; the function is independent of MTERFD2/MTERF4 and assembled mitochondrial ribosome large subunit (LSU). Targeted to LSU by MTERFD2/MTERF4 and probably is involved in a final step in ribosome biogenesis to ensure that SSU and LSU are assembled. In vitro can methylate 16S rRNA of the LSU; the methylation is enhanced by MTERFD/MTERF4.|||Mitochondrion http://togogenome.org/gene/10090:Ogfrl1 ^@ http://purl.uniprot.org/uniprot/Q8VE52 ^@ Similarity ^@ Belongs to the opioid growth factor receptor family. http://togogenome.org/gene/10090:Hadh ^@ http://purl.uniprot.org/uniprot/Q61425 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.|||Deficient mice display reduced levels of plasma glucose, elevated plasma insulin levels, increased plasma 3-hydroxybutyrylcarnitine and increased urinary 3-hydroxyglutarate. Islets isolated from knockout mice have increased amino acid-stimulated insulin secretion and higher sensitivity to leucine-stimulated insulin secretion.|||Expressed in liver, kidney, brain, and pancreatic islets.|||Homodimer (By similarity). Interacts with GLUD1; this interaction inhibits the activation of glutamate dehydrogenase 1 (GLUD1) (PubMed:20670938).|||Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) (By similarity). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion (PubMed:20670938).|||Mitochondrion matrix|||Succinylation at Lys-81, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5. http://togogenome.org/gene/10090:COX3 ^@ http://purl.uniprot.org/uniprot/P00416|||http://purl.uniprot.org/uniprot/Q7JCX7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 3 family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Fam151b ^@ http://purl.uniprot.org/uniprot/D3YUE4 ^@ Disruption Phenotype|||Function|||Similarity ^@ Belongs to the FAM151 family.|||Essential for survival of retinal photoreceptor cells.|||Mice show a degenerative retinal phenotype at week 15, characterized by patchy pigmentation of the retina. They have no photoreceptor function from eye opening. During development of the eye the correct number of cells are produced and the layers of the retina differentiate normally. However, after eye opening at P14, eyes exhibit signs of retinal stress and rapidly lose photoreceptor cells. http://togogenome.org/gene/10090:Nek8 ^@ http://purl.uniprot.org/uniprot/Q91ZR4 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Cytoplasm|||Defects in Nek8 are the cause of autosomal recessive juvenile polycystic kidney disease (ARJPKD).|||Interacts with PKD2; may regulate PKD2 targeting to the cilium (PubMed:18235101). Component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3 (By similarity). ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (By similarity). Interacts with ANKS3 (PubMed:25671767).|||Kidney, liver, and testis.|||Required for renal tubular integrity. May regulate local cytoskeletal structure in kidney tubule epithelial cells. May regulate ciliary biogenesis through targeting of proteins to the cilia. Plays a role in organogenesis and is involved in the regulation of the Hippo signaling pathway.|||centrosome|||cilium|||cytoskeleton http://togogenome.org/gene/10090:Ndufs4 ^@ http://purl.uniprot.org/uniprot/E9QPX3|||http://purl.uniprot.org/uniprot/Q9CXZ1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFS4 subunit family.|||Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme.|||Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme. Interacts with BCAP31 and TOMM40; the interaction mediates its translocation to the mitochondria; the interaction with BCAP31 is direct.|||Mitochondrion inner membrane|||Reduces the levels of assembled mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) and the rate of Complex I-driven oxygen consumption (PubMed:18396137, PubMed:25594180). Growth is retarded although activity and behavior are not affected during the first 4 weeks (PubMed:18396137). With aging, results in increasing lethargy, rapid deterioration of motor ability, weight loss followed by death (PubMed:18396137). Mitochondrial ultrastructure is normal, although large subsarcolemmal clusters of mitochondria are present in the soleus (PubMed:25594180). Exhibits glial lipid droplets accumulation in the olfactory bulb and vestibular nucleus prior to the onset of the physical signs of neurodegeneration (PubMed:25594180). Treatment with anti-oxidant treatment ameliorates the phenotype (PubMed:25594180). Conditional knockout in Vglut2-expressing glutamatergic neurons leads to decreased neuronal firing, brainstem inflammation, motor and respiratory deficits, and early death (PubMed:31403401). Conditional knockout in GABAergic neurons causes basal ganglia inflammation without motor or respiratory involvement, but accompanied by hypothermia and severe epileptic seizures preceding death (PubMed:31403401). Conditional knockout in cholinergic neurons has no effect on survival, body weight, or motor function (PubMed:31403401). http://togogenome.org/gene/10090:Vmn1r137 ^@ http://purl.uniprot.org/uniprot/D3YTY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Itm2a ^@ http://purl.uniprot.org/uniprot/Q61500 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ITM2 family.|||Expressed in mandibular condyles, in bone and in hair follicles. Strong expression in osteogenic tissues, such as neonatal calvaria, paws, tail and skin.|||Membrane http://togogenome.org/gene/10090:Itga7 ^@ http://purl.uniprot.org/uniprot/G3X9Q1|||http://purl.uniprot.org/uniprot/Q3TZS3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the integrin alpha chain family.|||Membrane http://togogenome.org/gene/10090:Mfsd14b ^@ http://purl.uniprot.org/uniprot/Q8CIA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Membrane http://togogenome.org/gene/10090:Prok2 ^@ http://purl.uniprot.org/uniprot/G3X8R6|||http://purl.uniprot.org/uniprot/Q14AB2|||http://purl.uniprot.org/uniprot/Q9QXU7 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by CLOCK and BMAL1 heterodimers and light; inhibited by period genes (PER1, PER2 and PER3) and cryptochrome genes (CRY1 and CRY2).|||Belongs to the AVIT (prokineticin) family.|||Expressed in mid-late pachytene spermatocytes at the stages VII, VIII and IX of the semiferous epithelial cycle.|||Expressed in the SCN and among a few other discrete brain areas, including the islands of Calleja, media l preoptic area of the hypothalamus and the shell of the nucleus accumbens. Highly expressed in testis. In the SCN, expression subjected to high amplitude of circadian oscillation.|||May function as an output molecule from the suprachiasmatic nucleus (SCN) that transmits behavioral circadian rhythm. May also function locally within the SCN to synchronize output. Potently contracts gastrointestinal (GI) smooth muscle (By similarity).|||Secreted http://togogenome.org/gene/10090:Apoc2 ^@ http://purl.uniprot.org/uniprot/Q05020|||http://purl.uniprot.org/uniprot/Q3UJG0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adult and fetal liver, intestine and peritoneal macrophages.|||Belongs to the apolipoprotein C2 family.|||Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase.|||Secreted http://togogenome.org/gene/10090:Ldlrap1 ^@ http://purl.uniprot.org/uniprot/Q8C142 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytosis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).|||Cytoplasm|||Interacts (via PID domain) with LDLR (via NPXY motif). Binds to soluble clathrin trimers. Interacts with AP2B1; the interaction mediates the association with the AP-2 complex (By similarity). Interacts with VLDLR (PubMed:12746448). Interacts with LRP2 (By similarity).|||Mice are extremely sensitive to cholesterol intake. LDLR are expressed at normal levels, but are sequestered at the hepatocyte surface. LDL internalization defect is caused by the inability of the LDLR to enter the endocytic cycle.|||The PID domain mediates interaction with the NPXY internalization motif of LDLR.|||The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1. http://togogenome.org/gene/10090:Or10ak16 ^@ http://purl.uniprot.org/uniprot/Q8VEY6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5ac16 ^@ http://purl.uniprot.org/uniprot/Q7TS40 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mboat2 ^@ http://purl.uniprot.org/uniprot/Q8R3I2 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophospholipid leading to the production of a phospholipid and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:18287005, PubMed:29196633). Catalyzes the acylation of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) and to a lesser extend lysophosphatidylethanolamine (1-acyl-sn-glycero-3-phosphoethanolamine or LPE) (PubMed:18287005, PubMed:29196633). Does not acylates lysophosphatidic acid (LPA) and lysophosphatidylserine (PubMed:18287005). Prefers oleoyl-CoA as the acyl donor (PubMed:18287005, PubMed:29196633). May be involved in chondrocyte differentiation (PubMed:29196633).|||Belongs to the membrane-bound acyltransferase family.|||Endoplasmic reticulum|||Highly expressed in epididymis, brain, testis, and ovary.|||Increased during chondrogenic differentiation.|||Membrane|||Partially inhibited by thimerosal. http://togogenome.org/gene/10090:Gjb2 ^@ http://purl.uniprot.org/uniprot/Q00977|||http://purl.uniprot.org/uniprot/Q3UJE9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels (By similarity). Forms heteromeric channels with GJB4 (PubMed:15692151). Interacts with CNST (PubMed:19864490).|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Detected in cochlea (at protein level) (PubMed:15692151). Detected in cochlea (PubMed:15692151). Liver, kidney, intestine, lung, spleen, stomach, testis and brain, but not heart and adult skeletal muscle.|||Detected in cochlea after 14.5 dpc. Detected in the spiral limbus in neoneates at 2, 8 and 12 days after birth, before the onset of hearing.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||Structural component of gap junctions (PubMed:15692151). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (By similarity). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:15692151).|||gap junction http://togogenome.org/gene/10090:Nrn1 ^@ http://purl.uniprot.org/uniprot/Q8CFV4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neuritin family.|||By synaptic activity through NMDA receptors and L-type voltage-sensitive calcium channels. By cAMP in active neurons.|||Cell membrane|||Component of the outer core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.|||Expressed in the brain (at protein level).|||Promotes neurite outgrowth and especially branching of neuritic processes in primary hippocampal and cortical cells.|||Synapse http://togogenome.org/gene/10090:Simc1 ^@ http://purl.uniprot.org/uniprot/E9Q6E9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Forms a heterodimer with SLF2. Interacts (via SIM domains) with SUMO1 and SUMO2. Interacts with CAPN3 and CTBP1. Interacts with SMC6 and ZNF451.|||Inhibits the protease activity of CAPN3. May play a role in SMC5-SMC6 complex recruitment for viral restriction. Forms a complex with SLF2 and this complex is required to recruit SMC5-SMC6 complex to PML nuclear bodies and sites of viral replication.|||PML body|||Skeletal muscle. http://togogenome.org/gene/10090:Uts2b ^@ http://purl.uniprot.org/uniprot/Q3V249|||http://purl.uniprot.org/uniprot/Q765I1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the urotensin-2 family.|||Potent vasoconstrictor.|||Secreted http://togogenome.org/gene/10090:Ublcp1 ^@ http://purl.uniprot.org/uniprot/Q8BGR9 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity. Recruited to the 19S regulatory particle of the 26S proteasome through its interaction with 19S component PSMD2/RPN1. Once recruited, dephosphorylates 19S component PSMC2/RPT1 which impairs PSMC2 ATPase activity and disrupts 26S proteasome assembly. Has also been reported to stimulate the proteolytic activity of the 26S proteasome.|||Nucleus|||The Ubiquitin-like domain mediates interaction with proteasomes. http://togogenome.org/gene/10090:Phtf2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Q1|||http://purl.uniprot.org/uniprot/Q8C9D2|||http://purl.uniprot.org/uniprot/Q8CB19 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Klra2 ^@ http://purl.uniprot.org/uniprot/A0FK58|||http://purl.uniprot.org/uniprot/E9Q433|||http://purl.uniprot.org/uniprot/Q9D3R1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Nbea ^@ http://purl.uniprot.org/uniprot/Q9EPN1 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat neurobeachin family.|||Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins. May have a role in membrane trafficking.|||Endomembrane system|||Forebrain, brainstem and cerebellum.|||Highly expressed in neonatal brain, levels decline in adults.|||Interacts with RII subunit of PKA.|||Membrane|||Postsynaptic cell membrane|||RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer. http://togogenome.org/gene/10090:Erp27 ^@ http://purl.uniprot.org/uniprot/Q9D8U3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein disulfide isomerase family.|||Does not contain a CXXC active site motif indicating that it is a catalytically redox-inactive member of the protein disulfide isomerase family.|||Endoplasmic reticulum lumen|||Interacts with PDIA3.|||Specifically binds unfolded proteins and may recruit protein disulfide isomerase PDIA3 to unfolded substrates. Binds protein substrates via a hydrophobic pocket in the C-terminal domain. May play a role in the unfolded stress response. http://togogenome.org/gene/10090:Mgat5b ^@ http://purl.uniprot.org/uniprot/Q765H6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 18 family.|||Brains from mutant mice display defective biosynthesis of O-mannosyl glycans (PubMed:22715095). Mutant mice that lack both Mgat5 and Mgat5b display no visible changes in brain anatomy, but their brains display defective biosynthesis of both O-mannosyl glycans and N-linked glycans (PubMed:22715095).|||Glycosyltransferase that acts on alpha-linked mannose of N-glycans and O-mannosyl glycans. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to the beta 1-6 linkage of the mannose residue of GlcNAc-beta1,2-Man-alpha on both the alpha1,3- and alpha1,6-linked mannose arms in the core structure of N-glycan (By similarity). Also acts on the GlcNAc-beta1,2-Man-alpha1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan (PubMed:22715095). Plays an active role in modulating integrin and laminin-dependent adhesion and migration of neuronal cells via its activity in the O-mannosyl glycan pathway.|||Golgi apparatus membrane|||Present in brain (at protein level) (PubMed:16413118). Predominantly expressed in hippocampus, superficial layers of the brain cortex, striatum, nucleus accumbens, a subset of nuclei in the thalamus, inferior colliculus, brain stem and cerebellum (PubMed:16413118, PubMed:22715095). http://togogenome.org/gene/10090:Trp53i11 ^@ http://purl.uniprot.org/uniprot/Q4QQM4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Entpd4 ^@ http://purl.uniprot.org/uniprot/Q8BSQ5|||http://purl.uniprot.org/uniprot/Q9DBT4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GDA1/CD39 NTPase family.|||Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner, with a preference for pyrimidines. Preferentially hydrolyzes UTP and TTP on UTP and TTP. AMP, ADP, ATP and UMP are not substrates. Preferentially activated by Ca(2+) over Mg(2+).|||Golgi apparatus membrane|||Has a broad substrate specificity with the ability of cleaving all nucleotide di- and triphosphates with the exception of adenosine di- and triphosphate (ADP and ATP). Preferentially hydrolyzes CTP, UDP, CDP, GTP and GDP. Can use either Ca(2+) or Mg(2+) equally.|||Lysosome membrane|||Ubiquitous.|||autophagosome membrane http://togogenome.org/gene/10090:Clca2 ^@ http://purl.uniprot.org/uniprot/Q8BG22 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basal cell membrane|||Belongs to the CLCR family.|||By 30-fold when cells are deprived of growth factors or anchorage in mammary epithelial cell. Down-regulated in metastatic mammary tumor cell lines.|||Cell junction|||Cell membrane|||Highly expressed in eye, spleen, lung, kidney, uterus, and endothelial cells. Weakly expressed in heart and throughout the gastrointestinal tract. Highly expressed in mammary cell lines. Its expression in immortalized cell line HC11 correlates with slow or arrested growth. Re-expression in mammary tumor cells reduces colony survival.|||N-glycosylated.|||Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4.|||The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.|||The translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a N-terminal and a C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity. http://togogenome.org/gene/10090:Nradd ^@ http://purl.uniprot.org/uniprot/Q8CJ26 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in lung and testis.|||Interacts with NGFR. Interacts with NTRK1. Interacts with SORT1.|||Modulates NTRK1 signaling. Can activate several intracellular signaling pathways, leading to activation of JUN. Promotes apoptosis. Promotes translocation of SORT1 to the cell membrane, and thereby hinders lysosomal degradation of SOTR1 and promotes its interaction with NGFR.|||Nucleus http://togogenome.org/gene/10090:Rhox4a2 ^@ http://purl.uniprot.org/uniprot/Q9D3I8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Spg7 ^@ http://purl.uniprot.org/uniprot/Q3ULF4 ^@ Caution|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent zinc metalloprotease. Plays a role in the formation and regulation of the mitochondrial permeability transition pore (mPTP) and its proteolytic activity is dispensable for this function (By similarity).|||According to PubMed:22563492, alternative splicing gives rise to an isoform (Paraplegin-2) which is identical to the sequence of the mature protein and localizes to the endoplasmic reticulum.|||Binds 1 zinc ion per subunit.|||Expressed in the brain and retina (at protein level).|||Forms heterooligomers with AFG3L1 and AFG3L2 (PubMed:22563492, PubMed:17101804, PubMed:19656850). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (By similarity). Interacts with AFG3L2; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:22563492, PubMed:19656850). Interacts with AFG3L1 (PubMed:19656850). Interacts with MAIP1. Interacts with VDAC1 and PPIF (By similarity).|||In the C-terminal section; belongs to the peptidase M41 family.|||In the N-terminal section; belongs to the AAA ATPase family.|||Mice are affected by a distal axonopathy of spinal and peripheral axons, characterized by axonal swelling and degeneration. Mitochondrial morphological abnormalities occur in synaptic terminals and in distal regions of axons long before the first signs of swelling and degeneration and correlate with onset of motor impairment during a rotarod test.|||Mitochondrion inner membrane|||Upon import into the mitochondrion, the N-terminal transit peptide is cleaved by the mitochondrial-processing peptidase (MPP) to generate an intermediate form which undergoes a second proteolytic cleavage mediated by proteases AFG3L1 and/or AFG3L2 removing an additional N-terminal fragment to generate the proteolytically active mature form. http://togogenome.org/gene/10090:Or51ai2 ^@ http://purl.uniprot.org/uniprot/Q9EPN9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mast1 ^@ http://purl.uniprot.org/uniprot/Q9R1L5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cell membrane|||Expressed in the brain (PubMed:30449657). Expressed in the developing cortical plate, the intermediate zone and corpus callosal fibers that cross the midline (PubMed:30449657). Detected at low levels in the testis, liver and spleen (PubMed:30449657). Expressed in proximity to neuronal nuclei throughout the cortex and cerebellum, and in the vascular endothelium. Also detected in ependymal cells, the choroid plexus, and in developing spermatid acrosomes.|||Expression in the brain begins at 12.5 dpc, peaks at 16.5 dpc, and decreases postnatally.|||Interacts with the microtubules (PubMed:30449657). Part of a low affinity complex that associates with, but is distinct from, the postsynaptic density. Interacts with SNTB2.|||Knockout mice do not show morphological defects.|||Microtubule-associated protein essential for correct brain development (PubMed:30449657). Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||axon|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Prm1 ^@ http://purl.uniprot.org/uniprot/A3KMD0|||http://purl.uniprot.org/uniprot/P02319 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protamine P1 family.|||Chromosome|||Cross-linked by interchain disulfide bonds around the DNA-helix.|||Nucleus|||Phosphorylated by SRPK1.|||Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.|||Testis. http://togogenome.org/gene/10090:Pigg ^@ http://purl.uniprot.org/uniprot/D3Z3Y1|||http://purl.uniprot.org/uniprot/D3Z4I0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGG/PIGN/PIGO family. PIGG subfamily.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:H2-Eb2 ^@ http://purl.uniprot.org/uniprot/Q3UUV9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Foxb2 ^@ http://purl.uniprot.org/uniprot/B9EII5|||http://purl.uniprot.org/uniprot/Q64733 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Expressed during embryogenesis.|||Nucleus|||Transcription factor. http://togogenome.org/gene/10090:Lpin1 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VLN4|||http://purl.uniprot.org/uniprot/A0A5F8MQ53|||http://purl.uniprot.org/uniprot/E9QKQ5|||http://purl.uniprot.org/uniprot/Q8CD95|||http://purl.uniprot.org/uniprot/Q91ZP3 ^@ Activity Regulation|||Disease Annotation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-459 and Lys-629 by KAT5 in response to fatty acids promotes translocation to the endoplasmic reticulum and synthesis of diacylglycerol.|||Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis and therefore controls the metabolism of fatty acids at different levels (PubMed:17158099). Acts also as nuclear transcriptional coactivator for PPARGC1A/PPARA regulatory pathway to modulate lipid metabolism gene expression (PubMed:16950137). Is involved in adipocyte differentiation (PubMed:16049017).|||Belongs to the lipin family.|||By fasting, glucocorticoids and diabetes in the liver in a PPARGC1A-dependent manner. Up-regulated during differentiation of 3T3-L1 pre-adipocytes.|||Contains one Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif essential for phosphatidate phosphatase activity.|||Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL), a transcriptional binding motif, which mediates interaction with PPARA.|||Cytoplasm|||Defects in Lpin1 are the cause of the fatty liver dystrophy phenotype (fld). Fld mutant mice are characterized by neonatal fatty liver and hypertriglyceridemia that resolve at weaning, and neuropathy affecting peripheral nerve in adulthood. Adipose tissue deficiency, glucose intolerance and increased susceptibility to atherosclerosis are associated with this mutation too. Two independent mutant alleles are characterized in this phenotype, fld and fld2j.|||Endoplasmic reticulum membrane|||Inhibited by N-ethylmaleimide treatment.|||Interacts (via LXXIL motif) with PPARA (PubMed:16950137). Interacts with PPARGC1A (PubMed:16950137). Interaction with PPARA and PPARGC1A leads to the formation of a complex that modulates gene transcription (PubMed:16950137). Interacts with MEF2C (PubMed:19753306).|||Mitochondrion outer membrane|||Nucleus|||Nucleus membrane|||Phosphorylated at multiple sites in response to insulin. Phosphorylation is controlled by the mTOR signaling pathway. Phosphorylation is decreased by epinephrine. Phosphorylation may not directly affect the catalytic activity but may regulate the localization. Dephosphorylated by the CTDNEP1-CNEP1R1 complex.|||Predominant isoform in the brain.|||Predominant isoform in the liver.|||Recruited at the mitochondrion outer membrane and is involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol.|||Specifically expressed in skeletal muscle. Also expressed prominently in adipose tissue, and testis. Lower expression also detected in kidney, lung, brain and liver.|||Sumoylation is important in brain and is marginal in other tissues. Sumoylation facilitates nuclear localization of isoform 2 in neuronals cells and its transcriptional coactivator activity. http://togogenome.org/gene/10090:Tent5d ^@ http://purl.uniprot.org/uniprot/B1ATX6 ^@ Similarity ^@ Belongs to the TENT family. http://togogenome.org/gene/10090:Acp6 ^@ http://purl.uniprot.org/uniprot/Q8BP40 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histidine acid phosphatase family.|||Hydrolyzes lysophosphatidic acid (LPA) containing a medium length fatty acid chain to the corresponding monoacylglycerol. Has highest activity with lysophosphatidic acid containing myristate (C14:0), monounsaturated oleate (C18:1) or palmitate (C16:0), and lower activity with C18:0 and C6:0 lysophosphatidic acid.|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Or51ac3 ^@ http://purl.uniprot.org/uniprot/Q3KPB0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Coa3 ^@ http://purl.uniprot.org/uniprot/Q9D2R6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Along with COX14, core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex. Interacts with MT-CO1/COX1, SMIM20, SURF1 and TIMM21.|||Belongs to the COA3 family.|||Core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. MITRAC complexes regulate both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. Required for efficient translation of MT-CO1 and mitochondrial respiratory chain complex IV assembly.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Zfp12 ^@ http://purl.uniprot.org/uniprot/Q7TSI0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Transcriptional repressor which suppresses activation protein 1 (AP-1)- and serum response element (SRE)-mediated transcriptional activity. http://togogenome.org/gene/10090:Vwa5b1 ^@ http://purl.uniprot.org/uniprot/A9Z1V5 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Ptprn ^@ http://purl.uniprot.org/uniprot/A6MDD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily.|||Membrane|||secretory vesicle membrane http://togogenome.org/gene/10090:Lzts2 ^@ http://purl.uniprot.org/uniprot/Q91YU6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LZTS2 family.|||Cytoplasm|||Interacts with KATNB1. Also interacts with CTNNB1, gamma-tubulin and KIF23.|||Negative regulator of katanin-mediated microtubule severing and release from the centrosome. Required for central spindle formation and the completion of cytokinesis. May negatively regulate axonal outgrowth by preventing the formation of microtubule bundles that are necessary for transport within the elongating axon. Negative regulator of the Wnt signaling pathway. Represses beta-catenin-mediated transcriptional activation by promoting the nuclear exclusion of beta-catenin.|||centrosome http://togogenome.org/gene/10090:Serping1 ^@ http://purl.uniprot.org/uniprot/P97290 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activation of the C1 complex is under control of the C1-inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. May inhibit chymotrypsin and kallikrein.|||Belongs to the serpin family.|||Interacts with MASP1.|||Secreted http://togogenome.org/gene/10090:Zbtb32 ^@ http://purl.uniprot.org/uniprot/Q9JKD9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||DNA-binding protein that binds to the to a 5'-TGTACAGTGT-3' core sequence. May function as a transcriptional transactivator and transcriptional repressor (By similarity). Probably exerts its repressor effect by preventing GATA3 from binding to DNA. May play a role in regulating the differentiation and activation of helper T-cells.|||Homodimer (via PTB domain). Interacts with the N-terminal of FANCC. Interacts with ZBTB16 (By similarity). Interacts with GATA3.|||Isoform 1 is testis-specific and is not expressed in lymphoid organs such as thymus or spleen. Isoform 2 is expressed in both B- and T-lymphoid cells.|||Nucleus|||The BTB (POZ) domain possesses repressor activity.|||The C-terminal zinc finger domain functions as a transcriptional transactivator. http://togogenome.org/gene/10090:Glra4 ^@ http://purl.uniprot.org/uniprot/Q2TB05|||http://purl.uniprot.org/uniprot/Q61603 ^@ Activity Regulation|||Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA4 sub-subfamily.|||Cell membrane|||Detected in the retina inner plexiform layer, especially at the border between layer three and four (at protein level) (PubMed:17154252).|||Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine. Channel opening is also triggered by taurine and beta-alanine (PubMed:10762330). Plays a role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents (Probable).|||Homopentamer (in vitro). Heteropentamer composed of GLRA4 and GLRB.|||Inhibited by strychnine (PubMed:10762330).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Perikaryon|||Postsynaptic cell membrane|||Synapse|||Synaptic cell membrane|||The alpha subunit binds strychnine.|||dendrite http://togogenome.org/gene/10090:Vmn1r213 ^@ http://purl.uniprot.org/uniprot/Q8R278 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Gm21943 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Gsto2 ^@ http://purl.uniprot.org/uniprot/Q8BW12|||http://purl.uniprot.org/uniprot/Q8K2Q2|||http://purl.uniprot.org/uniprot/Q9D2S1 ^@ Function|||Similarity ^@ Belongs to the GST superfamily. Omega family.|||Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA). http://togogenome.org/gene/10090:Cabs1 ^@ http://purl.uniprot.org/uniprot/Q8C633 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium-binding protein (PubMed:19208547). Essential for maintaining the structural integrity of the sperm flagella (PubMed:33440775).|||Cytoplasm|||Detected only in testis. Expressed from stages X to VIII of the seminiferous epithelial cycle. Expressed from step 13 to step 16 of spermatid development (at protein level).|||Down-regulated by Busulfan.|||Males exhibit significantly impaired sperm tail structure and subfertility (PubMed:33440775). Defects in sperm flagellar differentiation leads to an abnormal annulus and disorganization of the midpiece-principal piece junction (PubMed:33440775).|||Mitochondrion inner membrane|||acrosome|||flagellum http://togogenome.org/gene/10090:Fxyd5 ^@ http://purl.uniprot.org/uniprot/F8WJA1|||http://purl.uniprot.org/uniprot/P97808|||http://purl.uniprot.org/uniprot/Q3TDW1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FXYD family.|||Exhibits biphasic expression during development.|||Glycosylated.|||Involved in down-regulation of E-cadherin which results in reduced cell adhesion. Promotes metastasis (By similarity).|||Membrane|||Spleen, lung, skeletal muscle, and testis. http://togogenome.org/gene/10090:Or51h1 ^@ http://purl.uniprot.org/uniprot/E9Q547 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or6b2 ^@ http://purl.uniprot.org/uniprot/Q8VGU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ttbk1 ^@ http://purl.uniprot.org/uniprot/Q6PCN3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family.|||Cytoplasm|||Divalent metal cations. Mg(2+) or, to a lesser extent, Mn(2+), but not Ca(2+) or Zn(2+).|||Expressed in the brain. Strong expression in the cortical layers, the CA1 layers of the hippocampus and the granular layer of the cerebellum. Also expressed in the large cortical pyramidal cells in the temporal cortex, the CA1 pyramidal neurons and the cerebellum granular neurons.|||Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU (By similarity). http://togogenome.org/gene/10090:Ell ^@ http://purl.uniprot.org/uniprot/O08856 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ELL/occludin family.|||Cajal body|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts with ICE1 (via N-terminus domain). Interacts with ICE2. Interacts with AFF4; the interaction is direct. Interacts with EAF1 and EAF2 (By similarity). Interacts with USPL1 (By similarity).|||Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Specifically required for stimulating the elongation step of RNA polymerase II- and III-dependent snRNA gene transcription. ELL also plays an early role before its assembly into in the SEC complex by stabilizing RNA polymerase II recruitment/initiation and entry into the pause site. Required to stabilize the pre-initiation complex and early elongation. Specifically required for stimulating the elongation step of RNA polymerase II- and III-dependent snRNA gene transcription (By similarity). Elongation factor component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968).|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Iqch ^@ http://purl.uniprot.org/uniprot/Q9D2K4 ^@ Function|||Tissue Specificity ^@ Expressed in fetal and adult testis, in the spermatocytes and spermatids but not in somatic cells.|||May play a regulatory role in spermatogenesis. http://togogenome.org/gene/10090:Ccdc141 ^@ http://purl.uniprot.org/uniprot/E9Q8Q6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Between 11.5 and 15.5 dpc, CCDC141 is robustly expressed in migrating GnRH neurons, cells in the developing vomeronasal organ and olfactory axons. Detected also in sensory neurons, cell bodies and axons, in the dorsal root and trigeminal ganglia and within cortical structures within the CNS between 11.5 and 15.5 dpc.|||Cytoplasm|||Interacts with DISC1. Interacts preferentially with phosphorylated forms of myosin regulatory light chain (MRLC) (PubMed:20956536). Interacts (via the N-terminal region) with HDAC6; inhibits the deacetylase activity of HDAC6 (By similarity). Interacts with KIBRA (via the C-terminal region); retains AMPAR in the cytosol after internalization (PubMed:31730661).|||Knockout mice are born at the expected Mendelian frequency and are viable and fertile; they have normal body weight at birth and during the juvenile stage. Adult knockout mice have a normal appearance and exhibited no obvious changes in overall brain weight or morphology. However deficient mice show delayed cortical migration and abnormal behaviors associated with psychiatric disorders (PubMed:27737934). Deficient mice exhibit impaired recognition memory and spatial reference memory (PubMed:31730661).|||Phosphorylation at Thr-91 by PLK1 affects CCDC141 degradation.|||Plays a critical role in cortical radial and GnRH neurons migration during brain development (PubMed:20956536, PubMed:27014940). Regulates cortical radial migration by negatively controlling the activity of histone deacetylase 6 (HDAC6) and promotes centrosome maturation (PubMed:27737934). CAMDI is required for dilation formation of cortical neurons during radial migration (PubMed:34298015). Plays a critical role in learning and memory performance through regulation of AMPA-selective glutamate receptors (AMPARs) cell surface expression in competition with KIBRA (PubMed:27014940).|||Ubiquitinated and degradated by the CDC20-APC/C pathway. During brain development, CDC20-APC/C complex degrades CCDC141 after centrosome translocation into the dilated area. CCDC141 is restabilized in the dilation until the centrosome enters the dilation, at which point it is once again immediately destabilized by CDC20-APC/C complex. The oscillatory regulation of CCDC141 protein is needed for proper cortical migration.|||centrosome http://togogenome.org/gene/10090:Or8b43 ^@ http://purl.uniprot.org/uniprot/E9Q6Z7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hspa1b ^@ http://purl.uniprot.org/uniprot/P17879 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||Cytoplasm|||In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress.|||May be an auxiliary component of the CatSper complex (PubMed:17478420, PubMed:19516020). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2 (By similarity). Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed (By similarity). Interacts with TRIM5 (via B30.2/SPRY domain) (By similarity). Interacts with METTL21A (By similarity). Interacts with PRKN (By similarity). Interacts with FOXP3 (PubMed:23973223). Interacts with NOD2; the interaction enhances NOD2 stability (By similarity). Interacts with DNAJC9 (via J domain) (By similarity). Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes. Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively. Interacts with NEDD1 and SMAD3. Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105. Interacts with DNAJC8 (By similarity).|||Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation. Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle. Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation.|||Testis-specific.|||The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.|||centrosome http://togogenome.org/gene/10090:Ddn ^@ http://purl.uniprot.org/uniprot/Q80TS7 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in the developing podocytes during glomerulogenesis.|||Forms a ternary complex with MAGI2 and SH3KBP1; recruits DDN to the cytoplasm (By similarity). Interacts with MAGI1 (By similarity). Interacts with ACTN1 and may interact with WWC1 (By similarity). Interacts with the podocyte slit diaphragm proteins CD2AP, NPHS1 and NPHS2; the interaction with CD2AP and NPHS1 is direct.|||Nucleus|||Perikaryon|||Promotes apoptosis of kidney glomerular podocytes. Podocytes are highly specialized cells essential to the ultrafiltration of blood, resulting in the extraction of urine and the retention of protein.|||The 81 and 89 kDa forms are detected by an antibody raised against a C-terminal peptide arguing for alternative N-terminal sequences.|||Two forms of 81 kDa and 89 kDa are expressed in brain. The 81 kDa form is the only one found in kidney podocytes.|||dendritic spine membrane http://togogenome.org/gene/10090:Ramp3 ^@ http://purl.uniprot.org/uniprot/Q9WUP1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RAMP family.|||Cell membrane|||Expressed predominantly in the testis, embryonic and adult brain and in kidney.|||Interacts with GPER1 (By similarity). Heterodimer of CALCRL and RAMP3.|||Membrane|||Plays a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a GPER1-dependent manner. Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for adrenomedullin (AM) together with CALCRL. http://togogenome.org/gene/10090:Khk ^@ http://purl.uniprot.org/uniprot/P97328 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Belongs to the carbohydrate kinase PfkB family.|||Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate.|||Homodimer.|||Requires potassium. Inhibition by ADP (By similarity). http://togogenome.org/gene/10090:Tigd2 ^@ http://purl.uniprot.org/uniprot/Q0VBL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tigger transposable element derived protein family.|||Nucleus http://togogenome.org/gene/10090:Dnase2a ^@ http://purl.uniprot.org/uniprot/P56542|||http://purl.uniprot.org/uniprot/Q3UM14 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Absence of Dnase2 is a cause of severe fetal anemia and of perinatal lethality due to malformation of the diaphragm.|||Belongs to the DNase II family.|||Highly expressed in fetal liver macrophages.|||Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the clearance of nucleic acids generated through apoptosis, hence preventing autoinflammation. Necessary for proper fetal development and for definitive erythropoiesis in fetal liver and bone marrow, where it degrades nuclear DNA expelled from erythroid precursor cells.|||Lysosome http://togogenome.org/gene/10090:Slc6a15 ^@ http://purl.uniprot.org/uniprot/Q8BG16 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A15 subfamily.|||Detected throughout development, starting with the pre-implantation embryo.|||Functions as a sodium-dependent neutral amino acid transporter. Exhibits preference for methionine and for the branched-chain amino acids, particularly leucine, valine and isoleucine. Can also transport low-affinity substrates such as alanine, phenylalanine, glutamine and pipecolic acid (PubMed:16185194). Mediates the saturable, pH-sensitive and electrogenic cotransport of proline and sodium ions with a stoichiometry of 1:1. May have a role as transporter for neurotransmitter precursors into neurons. In contrast to other members of the neurotransmitter transporter family, does not appear to be chloride-dependent (By similarity).|||Membrane|||Mice are viable and fertile and fail to demonstrate any striking abnormality in motor and sensory functions. Other transporters could help to compensate for lost of SLC6A15.|||Significant expressed in brain, lung and kidney. In brain, mainly expressed int the cortex, the cerebellum and the brain stem. http://togogenome.org/gene/10090:Atxn2l ^@ http://purl.uniprot.org/uniprot/A0A0U1RPL0|||http://purl.uniprot.org/uniprot/Q3TGG2|||http://purl.uniprot.org/uniprot/Q7TQH0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Asymmetrically dimethylated. Probably methylated by PRMT1.|||Belongs to the ataxin-2 family.|||Cytoplasm|||Cytoplasmic granule|||Expressed in cerebellum.|||Interacts with MPL/TPOR and EPOR and dissociates after ligand stimulation. Interacts with DDX6, G3BP, and ATXN2. Interacts with PRMT1 (By similarity). Interacts with CIC and ATXN1 (PubMed:17322884).|||Involved in the regulation of stress granule and P-body formation.|||Membrane|||Nucleus speckle|||Thrombopoietin triggers the phosphorylation on tyrosine residues in a way that is dependent on MPL C-terminal domain. http://togogenome.org/gene/10090:Hirip3 ^@ http://purl.uniprot.org/uniprot/Q8BLH7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with HIRA. Weak interaction with histones H2B and H3. Interacts with CK2 (By similarity).|||May play a role in chromatin function and histone metabolism via its interaction with HIRA and histones.|||Nucleus|||Phosphorylated by CK2. http://togogenome.org/gene/10090:Ubqln1 ^@ http://purl.uniprot.org/uniprot/Q8R317 ^@ Domain|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Degraded during both macroautophagy and during chaperone-mediated autophagy (CMA).|||Dimerization is dependent upon the central region of the protein containing the STI1 domains and is independent of its ubiquitin-like and UBA domains.|||Endoplasmic reticulum|||Highly expressed in heart, brain, liver, smooth muscle and kidney.|||Monomer and homodimer. Heterodimer with UBQLN2 (By similarity). Binds CD47 (PubMed:10549293). Binds NBL1, GABRA1, GABRA2, GABRA3, GABRA6, GABRB1, GABRB2 and GABRB3. Binds UBE3A, BTRC, P4HB and MTOR. Interacts with the proteasome 19S subunit. Interacts (via ubiquitin-like domain) with TREX1; the interaction is direct and may control TREX1 subcellular location. Forms a complex with UBXN4 and VCP. Interacts (via UBA domain) with UBQLN4 (via ubiquitin-like domain). Found in a complex with UBQLN2 and MAP1LC3A/B/C. The monomeric form interacts with PSEN1 and PSEN2. Interacts with ORAI1. Interacts (via UBA domain) with TICAM1. Interacts with EPS15. Interacts (via UBA domain) with UBA52 and (via ubiquitin-like domain) with PSMD3 and PSMD4. Interacts with HERPUD1. Interacts with MAP1LC3A/B/C in the presence of UBQLN4. Interacts (via ubiquitin-like domain) with EPS15 (via UIM domains) and both the ubiquitinated and non-ubiquitinated forms can interact with EPS15. Interacts (via ubiquitin-like domain) with EPS15L1, HGS (via UIM domain) and STAM2 (via UIM domain) (By similarity). Interacts with BCL2L10/BCL-B; in the cytoplasm (By similarity).|||Nucleus|||Phosphorylated.|||Plays a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress (By similarity). Plays a key role in the regulation of the levels of PSEN1 by targeting its accumulation to aggresomes which may then be removed from cells by autophagocytosis (By similarity).|||Plays a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress.|||Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome. Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome. Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion. Negatively regulates the TICAM1/TRIF-dependent toll-like receptor signaling pathway by decreasing the abundance of TICAM1 via the autophagic pathway. Promotes the ubiquitination and lysosomal degradation of ORAI1, consequently down-regulating the ORAI1-mediated Ca2+ mobilization. Suppresses the maturation and proteasomal degradation of amyloid beta A4 protein (A4) by stimulating the lysine 63 (K63)-linked polyubiquitination. Delays the maturation of A4 by sequestering it in the Golgi apparatus and preventing its transport to the cell surface for subsequent processing (By similarity). Links CD47 to the cytoskeleton (PubMed:10549293). Ubiquitinates BCL2L10 and thereby stabilizes protein abundance (By similarity).|||Several sequencing errors.|||The UBA domain mediates binding to PSEN1 and PSEN2. It also binds ubiquitin with micromolar affinity, independently of polyubiquitin linkage type. Essential for its association with microtubule-associated protein 1 light chain 3 (MAP1LC3).|||The ubiquitin-like domain mediates its association with the subunits of the proteasome.|||Ubiquitinated.|||autophagosome http://togogenome.org/gene/10090:Or8b53 ^@ http://purl.uniprot.org/uniprot/E9Q413 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myh6 ^@ http://purl.uniprot.org/uniprot/B2RQQ1|||http://purl.uniprot.org/uniprot/Q02566 ^@ Caution|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).|||Muscle contraction.|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||Represents a conventional myosin. This protein should not be confused with the unconventional myosin-6 (MYO6).|||The cardiac alpha isoform is a 'fast' ATPase myosin, while the beta isoform is a 'slow' ATPase.|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||myofibril http://togogenome.org/gene/10090:Mrps18b ^@ http://purl.uniprot.org/uniprot/Q542W5|||http://purl.uniprot.org/uniprot/Q99N84 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS18 family. Mitochondrion-specific ribosomal protein mS40 subfamily.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Trim9 ^@ http://purl.uniprot.org/uniprot/E9Q524|||http://purl.uniprot.org/uniprot/E9QLH4|||http://purl.uniprot.org/uniprot/Q3TR28|||http://purl.uniprot.org/uniprot/Q8C7M3 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated.|||Belongs to the TRIM/RBCC family.|||Brain. Expression is higher in the cerebral cortex and hippocampus (at protein level). Its expression is mainly confined to the central nervous system. The developing neocortex, the dorsal thalamus, the midbrain, the basal area of the hindbrain and spinal cord show high level of expression during embryogenesis. In adult brain, it is detected in the Purkinje cells of the cerebellum, in the hippocampus, and in the cortex.|||Cytoplasm|||E3 ubiquitin-protein ligase which ubiquitinates itself in cooperation with an E2 enzyme UBE2D2/UBC4 and serves as a targeting signal for proteasomal degradation. May play a role in regulation of neuronal functions. May act as a regulator of synaptic vesicle exocytosis by controlling the availability of SNAP25 for the SNARE complex formation.|||First seen at 9.5 dpc. From 9.5 dpc to 11.5 dpc, it remains uniformly present in the ventral part of the entire neuroepithelium and in the dorsal root ganglia. A more restricted central nervous system (CNS) expression is observed at 13.5 dpc and 15.5 dpc when it is present in specific regions of the forebrain, midbrain, hindbrain and spinal cord.|||Interacts with SNAP25.|||May be due to a competing acceptor splice site and to an exon skipping.|||May be due to a competing donor splice site and ?.|||May be due to an exon inclusion.|||May be due to an intron retention.|||May be due to exon skipping.|||Synapse|||The coiled coil domain mediates the interaction with the N-terminal t-SNARE domain of SNAP25.|||cytoskeleton|||dendrite|||synaptic vesicle http://togogenome.org/gene/10090:Cdx4 ^@ http://purl.uniprot.org/uniprot/Q07424|||http://purl.uniprot.org/uniprot/Q78Z64 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Caudal homeobox family.|||Nucleus http://togogenome.org/gene/10090:Sox7 ^@ http://purl.uniprot.org/uniprot/P40646 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors. May be required for the survival of both hematopoietic and endothelial precursors during specification. May play a role in skeletal myogenesis and up-regulate the expression of muscle markers, such as PAX3/PAX7 and Meox1. Competes with GATA4 for binding and activation of the FGF3 promoter. Represses Wnt/beta-catenin-stimulated transcription. Probably acts by targeting CTNNB1 to proteasomal degradation. Binds the DNA sequence 5'-AACAAT-3'.|||Cytoplasm|||Expressed at least from 7.6 until 17.5 dpc. At 7.5 dpc, expressed in the yolk sac, as well as in the parietal and visceral endoderm and the embryonic mesoderm. At 8 dpc, expressed in somites and head region. At 9.5 dpc, expressed throughout vasculature. At 11.5 dpc, primarily expressed in the intersomitic vasculature. At 17.5 dpc, predominant expression in heart and lung. At that stage, also expressed in brain, cochlea, tongue, cartilage, lung, liver and vertebrae. During hemangioblast differentiation, transiently expressed in hemogenic endothelium cells and down-regulated in nascent blood precursors. May be expressed during the precursor stage of myogenic differentiation.|||Interacts with CTNNB1/beta-catenin; this interaction may lead to the proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription.|||Nucleus|||Predominantly expressed in ovary, lung and heart. In the ovary, restricted to oocytes (at protein level). Present both in mesenchymal and epithelial cells in some adult tissues, including ear.|||Up-regulated by VEGFA. http://togogenome.org/gene/10090:Lalba ^@ http://purl.uniprot.org/uniprot/A0A077S9Z6|||http://purl.uniprot.org/uniprot/P29752 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 22 family.|||Lactose synthase (LS) is heterodimer of a catalytic component, beta1,4-galactosyltransferase (beta4Gal-T1) and a regulatory component, alpha-lactalbumin (LA).|||Mammary gland specific. Secreted in milk.|||Regulatory subunit of lactose synthase, changes the substrate specificity of galactosyltransferase in the mammary gland making glucose a good acceptor substrate for this enzyme. This enables LS to synthesize lactose, the major carbohydrate component of milk. In other tissues, galactosyltransferase transfers galactose onto the N-acetylglucosamine of the oligosaccharide chains in glycoproteins.|||Secreted http://togogenome.org/gene/10090:Dffb ^@ http://purl.uniprot.org/uniprot/O54788 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Heterodimer of DFFA and DFFB (By similarity). Interacts with H1-1 (By similarity).|||Inhibited by DFFA (DFF45).|||Nuclease that induces DNA fragmentation and chromatin condensation during apoptosis. Degrades naked DNA and induces apoptotic morphology.|||Nucleus http://togogenome.org/gene/10090:Il22 ^@ http://purl.uniprot.org/uniprot/Q9JJY9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-10 family.|||Cytokine that plays a critical role in modulating tissue responses during inflammation (PubMed:35525330, PubMed:33852830). Plays an essential role in the regeneration of epithelial cells to maintain barrier function after injury and for the prevention of further tissue damage (PubMed:33912578). Unlike most of the cytokines, has no effect on immune cells. Signals through a heterodimeric receptor composed of two subunits, the specific receptor IL22RA1 which is present on non-immune cells in many organs and the shared subunit IL10RB. Ligation of IL22RA1 with IL22 induces activation of the tyrosine kinases JAK1 and TYK2, which in turn activates STAT3. In turn, promotes cell survival and proliferation through STAT3, ERK1/2 and PI3K/AKT pathways. Promotes phosphorylation of GSK3B at 'Ser-9' and CTTN (PubMed:24742671). Promotes epithelial cell spreading (PubMed:24742671).|||Deletion mice have an enhanced response to agricultural dust as evidenced by an exacerbated increase in infiltrating immune cells and lung pathology as compared to wild-type controls (PubMed:35525330). In addition, T-gondii-infected mice display a significant defect of the epithelial barrier and an increase in macromolecular permeability when compared to wild-type mice (PubMed:33912578).|||Secreted http://togogenome.org/gene/10090:Svep1 ^@ http://purl.uniprot.org/uniprot/A2AVA0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed from 11 dpc to 17 dpc in embryos.|||May play a role in the cell attachment process.|||Membrane|||Present in stromal osteogenic cells. Expressed at much higher level in stromal osteogenic cells at low density compared to cells grown at higher densities (at protein level). Highly expressed in lung and placenta. Also expressed in bone and periosteum, but not in cartilage and skeletal muscle. Weakly or not expressed in other tissues.|||Secreted http://togogenome.org/gene/10090:Cyp26b1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SUV4|||http://purl.uniprot.org/uniprot/Q811W2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (Probable). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (By similarity). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling (Probable). Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (By similarity). Involved in the convertion of atRA to all-trans-4-oxo-RA (Probable). Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (Probable). Shows preference for the following substrates: atRA > 9-cis-RA > 13-cis-RA (By similarity). Plays a central role in germ cell development: acts by degrading RAs in the developing testis, preventing STRA8 expression, thereby leading to delay of meiosis (PubMed:16461896, PubMed:16574820, PubMed:19838304). Required for the maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells, inducing arrest in G0 phase of the cell cycle and preventing meiotic entry (PubMed:16574820, PubMed:16461896, PubMed:19838304). Plays a role in skeletal development, both at the level of patterning and in the ossification of bone and the establishment of some synovial joints (PubMed:22019272). Essential for postnatal survival (PubMed:16461896, PubMed:16574820, PubMed:19838304).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Germ cells enter meiosis precociously in embryonic testes, due to strong-up-regulation of Stra8.|||Has also a significant activity in oxidation of tazarotenic acid and may therefore metabolize that xenobiotic in vivo.|||In the embryonic male gonad, expressed in somatic cells as early as 11.5 dpc and persist throughout development. Expression is detected in peritubular myoepithelial cells in the postnatal testis, while expression is absent in developing and adult ovaries.|||Microsome membrane http://togogenome.org/gene/10090:Btbd35f21 ^@ http://purl.uniprot.org/uniprot/Q99N64 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CUL3.|||Nucleus matrix|||Possible function in spermatogenesis. Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. http://togogenome.org/gene/10090:Slc25a47 ^@ http://purl.uniprot.org/uniprot/Q6IS41 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial NAD(+) transporter that acts as a 'metabolic gate' in hepatic lipogenesis. Provides NAD(+) substrate to mitochondrial SIRT3 deacetylase and enables its NAD(+)-dependent activities in mitochondrial energy metabolism. This triggers downstream activation of PRKAA1/AMPK-alpha signaling cascade that negatively regulates sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. May transport other mitochondrial metabolites having an aromatic nucleotide and phosphate groups, such as acetyl-CoA. Does not transport amino acids. The transport mechanism remains to be elucidated.|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Mutant mice show increased hepatic steatosis upon methionine- and choline-deficient or high-fat diet associated with increased hepatic lipid droplets and triglycerides and cholesterol levels. They spontaneously develop hepatocellular carcinomas.|||SLC25A47 is transcriptionally up-regulated in response to antihyperglycemic drug metformin. Promotes metformin pharmacological effects.|||Specifically expressed in liver (at protein level). http://togogenome.org/gene/10090:Or4d11 ^@ http://purl.uniprot.org/uniprot/Q8VFV0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ttc8 ^@ http://purl.uniprot.org/uniprot/Q8VD72 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed at 12 dpc in ciliated structures, including maturing (stages X and XI) spermatids, the connecting cilium of the retina and bronchial epithelial cells. At 14 and 16 dpc, detected in the telencephalon, with prominent expression at the developing ependymal cell layer and the olfactory epithelium.|||Isoform 1 is retina-specific whereas isoform 2 is ubiquitously expressed.|||Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1. Interacts with CCDC28B. Interacts with PKD1.|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization (By similarity).|||centriolar satellite|||centriole|||cilium|||cilium membrane http://togogenome.org/gene/10090:Serpina11 ^@ http://purl.uniprot.org/uniprot/E9QK54|||http://purl.uniprot.org/uniprot/E9QLL8|||http://purl.uniprot.org/uniprot/Q3UEP8|||http://purl.uniprot.org/uniprot/Q8CIE0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Secreted http://togogenome.org/gene/10090:Or6b9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0M0|||http://purl.uniprot.org/uniprot/P34986 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor.|||Olfactory epithelium. http://togogenome.org/gene/10090:Gm21184 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Slc5a7 ^@ http://purl.uniprot.org/uniprot/Q8BGY9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although morphologically normal at birth, knockout mice become immobile, breathe irregularly, appear cyanotic, and die within an hour. Mice had developmental changes in neuromuscular junction morphology reminiscent of changes in mutant mice lacking ACh synthesis.|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Choline uptake activity is regulated by SLC5A7/CHT1 internalization (inactive form) from the cell surface and recycling of internalized SLC5A7/CHT1 into the cell surface (active form) (By similarity). Activated by extracellular chloride ion (By similarity). Specifically inhibited by nanomolar concentrations of hemicholinium 3 (PubMed:11709061, PubMed:15173594).|||Early endosome membrane|||Found in spinal cord, brain-stem, mid-brain and striatum (PubMed:11709061). Specific for cholinergic neurons (PubMed:11709061).|||High-affinity Na(+)-coupled choline transmembrane symporter (PubMed:11709061, PubMed:15173594). Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry (By similarity). Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion (By similarity). Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release (By similarity). SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials (PubMed:11709061, PubMed:15173594). Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity (By similarity).|||Homooligomerizes at cell surface. Interacts with SEC14L1; may regulate SLC5A7.|||Phosphorylated by PKC and dephosphorylated by PP1/PP2A.|||Presynaptic cell membrane|||The C-terminal dileucine-like motif (DKTILV) controls SLC5A7/CHT1 internalization in clathrin-coated vesicles to early endosomes as well as choline transporter activity.|||axon|||synaptic vesicle membrane http://togogenome.org/gene/10090:Cdk16 ^@ http://purl.uniprot.org/uniprot/Q04735|||http://purl.uniprot.org/uniprot/Q3TM24|||http://purl.uniprot.org/uniprot/Q543G3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Found in a complex containing CABLES1, CDK17 and TDRD7. Interacts with BRSK2. Identified in a complex with NSF, syntaxin-1, synaptotagmin, SYN1, SYP and CDK5R1 (By similarity). Interacts with YWHAH, YWHAQ and YWHAZ. Interacts with CCNY; this increases the CDK16 kinase activity. Interacts with NSF.|||Highly expressed in testis and brain, and detected at lower levels in heart, skeletal muscle, adipose tissue, lung, spleen and pancreas (at protein level). Ubiquitous with highest levels in testis and brain, with longer form predominant in all tissues except the testis.|||No visible phenotype in females; they are viable and fertile. Male mice are infertile, due to a defect in late stages of spermatogenesis.|||Phosphorylation at Ser-153 inhibits kinase activity.|||Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Can phosphorylate CCNY at 'Ser-336' (in vitro) (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development.|||secretory vesicle|||synaptosome http://togogenome.org/gene/10090:Lilrb4b ^@ http://purl.uniprot.org/uniprot/Q61450 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed on mast cells (at protein level) (PubMed:10630292, PubMed:10982834). Also expressed at much lower levels on natural killer cells (at protein level) (PubMed:10982834).|||In contrast to the related Lilrb4a protein, does not contain any copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM).|||Monomer and homodimer.|||Plays a role in mast cell activation. http://togogenome.org/gene/10090:Or8k38 ^@ http://purl.uniprot.org/uniprot/Q7TR64 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ethe1 ^@ http://purl.uniprot.org/uniprot/Q9DCM0 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||First described as a protein that can shuttle between the nucleus and the cytoplasm and suppress p53-induced apoptosis by sequestering the transcription factor RELA/NFKB3 in the cytoplasm and preventing its accumulation in the nucleus (By similarity). Sulfur dioxygenase that plays an essential role in hydrogen sulfide catabolism in the mitochondrial matrix. Hydrogen sulfide (H(2)S) is first oxidized by SQRDL, giving rise to cysteine persulfide residues. ETHE1 consumes molecular oxygen to catalyze the oxidation of the persulfide, once it has been transferred to a thiophilic acceptor, such as glutathione (R-SSH). Plays an important role in metabolic homeostasis in mitochondria by metabolizing hydrogen sulfide and preventing the accumulation of supraphysiological H(2)S levels that have toxic effects, due to the inhibition of cytochrome c oxidase.|||Homodimer. Monomer. Interacts with TST. May interact with RELA.|||Mice are born at slightly less than the expected Mendelian rate. Pups display growth arrest at about 15 days after birth and die five to six weeks after birth. Mice exhibit elevated levels of hydrogen sulfide (H(2)S) in liver, muscle and brain, together with increased urinary levels of ethylmalonic acid and thiosulfate. Their mitochondria show decreased cytochrome c oxidase activity, probably due to the toxic effects of supraphysiological levels of hydrogen sulfide.|||Mitochondrion matrix|||Nucleus http://togogenome.org/gene/10090:Krtap19-2 ^@ http://purl.uniprot.org/uniprot/Q925I0 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 19 family.|||Expression in skin and hair follicle is regulated by HOXC13 and by GATA3.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins.|||Strong expression in narrowly defined pattern restricted to the lower and middle cortical regions of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). http://togogenome.org/gene/10090:Runx3 ^@ http://purl.uniprot.org/uniprot/Q3U1Q3 ^@ Function|||Subcellular Location Annotation ^@ Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX.|||Nucleus http://togogenome.org/gene/10090:Ppp1r14d ^@ http://purl.uniprot.org/uniprot/Q7TT52 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PP1 inhibitor family.|||Cytoplasm|||Inhibitor of PPP1CA. Has inhibitory activity only when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction (By similarity).|||Isoform 1 is detected in intestine, kidney, lung, spleen, stomach and brain. Isoform 2 is detected in testis.|||Phosphorylated on several residues. http://togogenome.org/gene/10090:Or8b8 ^@ http://purl.uniprot.org/uniprot/B2RQ58|||http://purl.uniprot.org/uniprot/Q60882 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Tle1 ^@ http://purl.uniprot.org/uniprot/Q5SQA2|||http://purl.uniprot.org/uniprot/Q5SQA3|||http://purl.uniprot.org/uniprot/Q5SQA4|||http://purl.uniprot.org/uniprot/Q62440|||http://purl.uniprot.org/uniprot/Q6PFG2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat Groucho/TLE family.|||Cytoplasm|||Highly expressed in liver and lung. Detected at slightly lower levels in heart, brain, kidney and testis. Detected in fetal and adult stomach and small intestine, in adult ileum, duodenum and colon. Expressed in bone marrow-derived macrophages (PubMed:23990468).|||Homooligomer and heterooligomer with other family members. Binds RUNX1, RUNX3, FOXA2, KDM6A, UTY, histone H3, HESX1, ESRRG and the NF-kappa-B subunit RELA. Interacts with HES1 (via WRPW motif) (By similarity). Binds TCF7, LEF1, TCF7L1 and TCF7L2 (PubMed:11266540). Interacts with SIX3 (By similarity). Interacts with EFNB1. Interacts with TLE4 (PubMed:16314515). Interacts with FOXG1/BF-1; the interaction is inhibited by TLE6/GRG6 (PubMed:16314515).|||Most abundant at the base of the crypts of Lieberkuhn in the small intestine.|||Nucleus|||Phosphorylated, probably by CDK1. The degree of phosphorylation varies throughout the cell cycle, and is highest at the G2/M transition. Becomes hyperphosphorylated in response to cell differentiation and interaction with HES1 or RUNX1.|||Transcriptional corepressor that binds to a number of transcription factors. Inhibits NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, and by CTNNB1 and TCF family members in Wnt signaling. Enhances FOXG1/BF-1- and HES1-mediated transcriptional repression (PubMed:16314515). The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Unusual function as coactivator for ESRRG (By similarity).|||Ubiquitinated by XIAP/BIRC4.|||WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain. http://togogenome.org/gene/10090:Ripor2 ^@ http://purl.uniprot.org/uniprot/A6PW28|||http://purl.uniprot.org/uniprot/Q80U16 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization (PubMed:25588844, PubMed:27269051). Plays a role in fetal mononuclear myoblast differentiation by promoting filopodia and myotube formation (PubMed:17150207). Maintains naive T lymphocytes in a quiescent state and prevents chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration (By similarity). Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion (PubMed:25588844). Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear (PubMed:27269051). Plays a role for maintaining the structural organization of the basal domain of stereocilia (PubMed:27269051). Involved in mechanosensory hair cell function (PubMed:27269051). Required for normal hearing (PubMed:27269051).|||Apical cell membrane|||Belongs to the RIPOR family.|||Cytoplasm|||Expressed in the cochlea (PubMed:24958875, PubMed:32631815). Expressed in inner hair cells and outer hair cells and Hensen's cells (at protein level) (PubMed:27269051, PubMed:32631815). Expressed in the brain, cerebellum, spinal cord, retina, heart, spleen liver, kidney, bladder, muscle and lung (PubMed:24958875, PubMed:27269051). Expressed in the cochlea of the inner ear (PubMed:24958875, PubMed:27269051).|||Homooligomer; homooligomerization is regulated by RHOC and leads to the formation of concatemers through the association of N- and C-termini (PubMed:27269051, PubMed:32631815). Interacts (phosphorylated form) with 14-3-3 proteins; these interactions occur during myogenic cell differentiation and also induces T cell proliferation arrest (By similarity). Interacts (phosphorylated form) with HDAC6; this interaction occurs during early myogenic differentiation, prevents HDAC6 to deacetylate tubulin and also induces T cell proliferation arrest (By similarity). Interacts with DYSF; this interaction occurs during early myogenic differentiation (PubMed:24687993). Interacts with MYOF (By similarity). Interacts (via active GTP- or inactive GDP-bound forms) with RHOA; this interaction is direct, blocks the loading of GTP to RHOA and decreases upon chemokine CCL19 stimulation in primary T lymphocytes (PubMed:27269051). Interacts with RHOC (PubMed:27269051, PubMed:32631815). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a chemokine-dependent manner and does not compete for binding of RIPOR2 with RHOA nor blocks inhibition of RIPOR2-mediated RHOA activity (By similarity). Interacts with YWHAE (By similarity). Interacts with YWHAQ (By similarity).|||Mice are deaf at 4 weeks of age (PubMed:27269051). Show abnormal hair bundle morphology and polarity and stereociliary growth in the cochlea of the inner ear (PubMed:27269051). Display mislocalization of protein TPRN to the base of stereocilia (PubMed:27269051). Show reduced mechanotransduction currents in hair bundles of outer hair cells (PubMed:27269051). Mice show impaired neutrophil chemotaxis, increased neutrophil adhesion to endothelial cell and reduced neutrophil infiltration into inflamed peritonea (PubMed:25588844). Display increased chemokine-induced RHOA activity and mislocalization of myosin light chain MYL2 in neutrophils (PubMed:25588844).|||Phosphorylated. Chemokine-induced phosphorylation in neutrophils occurs in a PKC- and AKT-dependent manner, resulting in RIPOR2 interaction with YWHAB and stabilization. Phosphorylated by PKCA, AKT1 and MAPKAPK1A; in vitro.|||Up-regulated during regenerating muscle tissue.|||cytoskeleton|||filopodium|||stereocilium|||stereocilium membrane http://togogenome.org/gene/10090:Thegl ^@ http://purl.uniprot.org/uniprot/Q9DA15 ^@ Disruption Phenotype ^@ Deficient mice are viable and have normal fertility. http://togogenome.org/gene/10090:Arhgap21 ^@ http://purl.uniprot.org/uniprot/Q6DFV3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell junction|||Cytoplasmic vesicle membrane|||Functions as a GTPase-activating protein (GAP) for RHOA and CDC42. Downstream partner of ARF1 which may control Golgi apparatus structure and function. Also required for CTNNA1 recruitment to adherens junctions (By similarity).|||Golgi apparatus membrane|||Interacts with CTNNA1 (By similarity). Interacts with GTP-bound ARF1 and probably ARF6.|||Sumoylated with SUMO2 and SUMO3 in proliferating lymphocytes.|||cytoskeleton http://togogenome.org/gene/10090:Dpf2 ^@ http://purl.uniprot.org/uniprot/Q61103 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Already detected at embryonic day 8.5. Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5 dpc-16.5 dpc.|||Belongs to the requiem/DPF family.|||Cytoplasm|||In embryo, highest levels are seen in brain, eyes, thymus and olfactory epithelium in nose, whereas several other tissues, including the musculoskeletal system, show moderate expression. In adult, higher expression in testis, medium in thymus and spleen, lower in certain parts of the brain as the hippocampus. No expression in adult heart, lung, liver, duodenum and kidney.|||Interacts with the nucleosomes, in particular nucleosomes bearing histone H3 crotonylated at 'Lys-14' (H3K14cr) for which DPF2 has high affinity. Also interacts (via PHD-type zinc finger domains) with histone H3 butyrylated at 'Lys-14' (H3K14bu), histone H3 propionylated at 'Lys-14' (H3K14pr), and histone H3 acetylated at 'Lys-14' (H3K14ac). Interacts with histone H3 acetylated at 'Lys-9' (H3K9ac), histone H3 di-methylated at 'Lys-9' (H3K9me2), and histone H3 tri-methylated at 'Lys-9' (H3K9me3). Interacts with histone H4 acetylated at 'Lys-12' (H4K12ac). Interacts with histone H4 acetylated at 'Lys-16' (H4K16ac). Interacts with SWI/SNF complex components. Interacts with SMARCA2, SMARCA4, SMARCB1 and SMARCD1. Interacts with SMARCC1, SMARCC2 and ACTL6A. Interacts with RUNX1.|||Nucleus|||Plays an active role in transcriptional regulation by binding modified histones H3 and H4. Is a negative regulator of myeloid differentiation of hematopoietic progenitor cells (By similarity). Might also have a role in the development and maturation of lymphoid cells (PubMed:7961935). Involved in the regulation of non-canonical NF-kappa-B pathway (By similarity). http://togogenome.org/gene/10090:Or2y16 ^@ http://purl.uniprot.org/uniprot/Q8VFA3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ilrun ^@ http://purl.uniprot.org/uniprot/Q3TT38 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with IRF3; the interaction inhibits IRF3 binding to its DNA consensus sequence.|||Negative regulator of innate antiviral response. Blocks IRF3-dependent cytokine production such as IFNA, IFNB and TNF. Interacts with IRF3 and inhibits IRF3 recruitment to type I IFN promoter sequences while also reducing nuclear levels of the coactivators EP300 and CREBBP.|||Nucleus http://togogenome.org/gene/10090:Or1aa2 ^@ http://purl.uniprot.org/uniprot/Q8VEU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:P4ha2 ^@ http://purl.uniprot.org/uniprot/Q5SX74|||http://purl.uniprot.org/uniprot/Q5SX75|||http://purl.uniprot.org/uniprot/Q60716 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the P4HA family.|||Binds 1 Fe(2+) ion per subunit.|||Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.|||Endoplasmic reticulum lumen|||Expressed at least in brain, heart and lung.|||Heterotetramer of two alpha-2 chains and two beta chains (P4HB) (the beta chain is the multi-functional PDI), where P4HB plays the role of a structural subunit; this tetramer catalyzes the formation of 4-hydroxyproline in collagen.|||Inhibited by poly(L-proline) only at very high concentrations. http://togogenome.org/gene/10090:Aoc2 ^@ http://purl.uniprot.org/uniprot/Q812C9 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the copper/topaquinone oxidase family.|||Binds 1 copper ion per subunit.|||Binds 2 calcium ions per subunit.|||Contains 1 topaquinone per subunit.|||Has a monoamine oxidase activity with substrate specificity for 2-phenylethylamine and tryptamine. May play a role in adipogenesis. May be a critical modulator of signal transmission in retina (By similarity).|||Homodimer; disulfide-linked (By similarity). Forms a heterodimer with AOC3 (By similarity).|||Significantly much highly expressed in retina.|||Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. http://togogenome.org/gene/10090:Mr1 ^@ http://purl.uniprot.org/uniprot/Q8HWB0 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antigen-presenting molecule specialized in displaying microbial pyrimidine-based metabolites to alpha-beta T cell receptors (TCR) on innate-type mucosal-associated invariant T (MAIT) cells. In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TRAV1 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (PubMed:20581831, PubMed:15802267). Signature pyrimidine-based microbial antigens are generated via non-enzymatic condensation of metabolite intermediates of the riboflavin pathway with by-products arising from other metabolic pathways such as glycolysis. Typical potent antigenic metabolites are 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or methylglyoxal by-products, respectively. May present microbial antigens to various TRAV1-negative MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin. Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (By similarity). During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora (PubMed:12634786, PubMed:31113973). Acts as an immune sensor of cancer cell metabolome. May present a tumor-specific or -associated metabolite essential for cancer cell survival to a pan-cancer TCR on a non-MAIT CD8-positive T cell clone, triggering T cell-mediated killing of a wide range of cancer cell types (By similarity).|||Belongs to the MHC class I family.|||Cell membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Heterotrimer that consists of MR1, B2M and metabolite antigen (By similarity). Forms reversible covalent Schiff base complexes with the microbial metabolite, which serve as a molecular switch triggering complete folding, stable association with B2M and translocation of the ternary complex from endoplasmic reticulum to the plasma membrane (By similarity). On antigen-presenting cells, the ternary complex interacts with TCR on CD8-positive T cells (By similarity). The molecular machinery involved in antigen processing remains unknown, but appears to be TAP1-TAP2 and proteasome-independent. Structurally, MR1-B2M heterodimer adopts a topology similar to classical MHC class I molecules, with alpha-1 and alpha-2 domains of MR1 forming the antigen-binding cleft composed of two alpha-helices resting on a floor of 7-stranded anti-parallel beta-pleated sheet (By similarity).|||Highly expressed thymus. Expressed in liver, kidney, spleen, heart, brain, lung, skeletal muscle and testis.|||Late endosome membrane|||MR1 is detected in an open versus folded conformation. Only the folded MR1 conformer activates MAIT cells.|||Mutant mice lack invariant MAIT cells due to impaired thymic selection. They show normal development of T, B and NK cells.|||N-glycosylated.|||Reported to be associated with components of the peptide-loading complex, TAPBP, CALR, CANX and PDIA3 (PubMed:12794138). This association in primary cells and its functional relevance is disputable, given that antigen presentation and MAIT cell activation is shown to be TAP1-TAP2 and proteasome-independent.|||The alpha-1 domain is a structural part of antigen-binding cleft.|||The alpha-2 domain is a structural part of antigen-binding cleft. http://togogenome.org/gene/10090:Plppr1 ^@ http://purl.uniprot.org/uniprot/Q8BFZ2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Cell membrane|||Has no 2-lysophosphatidate/LPA phosphatase activity. This is supported by the fact that the phosphatase sequence motifs as well as the His residue acting as a nucleophile in active phosphatases of the PA-phosphatase related phosphoesterase family are not conserved.|||May play a role in neurite outgrowth and neurogenesis.|||neuron projection http://togogenome.org/gene/10090:Pcdh19 ^@ http://purl.uniprot.org/uniprot/Q80TF3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Calcium-dependent cell-adhesion protein.|||Cell membrane|||Homodimer; antiparallel. http://togogenome.org/gene/10090:Eif4ebp3 ^@ http://purl.uniprot.org/uniprot/Q80VV3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF4E-binding protein family.|||Cytoplasm|||Interacts with EIF4E (By similarity). Interacts with RPA2 (via N-terminus); the interaction enhances EIF4EBP3-mediated inhibition of EIF4E-mediated mRNA nuclear export (By similarity).|||Nucleus|||Phosphorylated.|||Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: the hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repression of translation. In contrast, the hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Inhibits EIF4E-mediated mRNA nuclear export (By similarity). http://togogenome.org/gene/10090:Snrpa1 ^@ http://purl.uniprot.org/uniprot/P57784 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the U2 small nuclear ribonucleoprotein A family.|||Identified in the spliceosome B complex. Identified in the spliceosome C complex. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2. Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRNP70, SNRPA1, SRRM1 and TRA2B. Contributes to the binding of stem loop IV of U2 snRNA with SNRPB2.|||Involved in pre-mRNA splicing as component of the spliceosome. Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA.|||Nucleus http://togogenome.org/gene/10090:Zfp821 ^@ http://purl.uniprot.org/uniprot/Q6PD05 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Gata5 ^@ http://purl.uniprot.org/uniprot/P97489 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Transcription factor required during cardiovascular development (By similarity). Plays an important role in the transcriptional program(s) that underlies smooth muscle cell diversity (PubMed:9119112). Binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C transcriptional enhancer (By similarity). http://togogenome.org/gene/10090:Aqp6 ^@ http://purl.uniprot.org/uniprot/Q8C4A0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cytoplasmic vesicle membrane|||Forms a water-specific channel that participates in distinct physiological functions such as glomerular filtration, tubular endocytosis and acid-base metabolism. http://togogenome.org/gene/10090:Cxcl9 ^@ http://purl.uniprot.org/uniprot/P18340 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||By interferon gamma.|||May be a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response.|||Secreted http://togogenome.org/gene/10090:Kcnma1 ^@ http://purl.uniprot.org/uniprot/A0A087WQ41|||http://purl.uniprot.org/uniprot/A0A087WQN5|||http://purl.uniprot.org/uniprot/A0A087WRS4|||http://purl.uniprot.org/uniprot/A0A286YD35|||http://purl.uniprot.org/uniprot/A0A286YDM6|||http://purl.uniprot.org/uniprot/Q08460 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily.|||Cell membrane|||Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation (By similarity).|||Homotetramer; which constitutes the calcium-activated potassium channel. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Interacts with gamma subunits LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma subunits are accessory, and modulate its activity (By similarity). Interacts with RAB11B.|||Membrane|||Palmitoylation by ZDHHC22 and ZDHHC23 within the intracellular linker between the S0 and S1 transmembrane domains regulates localization to the plasma membrane. Depalmitoylated by LYPLA1 and LYPLAL1, leading to retard exit from the trans-Golgi network (By similarity).|||Phosphorylated (Probable). Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity.|||Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).|||The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+).|||The S0 segment is essential for the modulation by the accessory beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4.|||The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor.|||The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensors regions required for activation of the channel.|||The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation (By similarity).|||The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium.|||The protein was initially thought to contain two functionally distinct parts: The core channel (from the N-terminus to the S9 segment) that mediates the channel activity, and the cytoplasmic tail (from the S9 segment to the C-terminus) that mediates the calcium sensing. The situation is however more complex, since the core channel contains binding sites for Ca(2+) and Mg(2+). http://togogenome.org/gene/10090:Slc44a1 ^@ http://purl.uniprot.org/uniprot/A2AMH3|||http://purl.uniprot.org/uniprot/A2AMH4|||http://purl.uniprot.org/uniprot/Q6X893 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CTL (choline transporter-like) family.|||Cell membrane|||Choline transporter.|||Choline/H+ antiporter (PubMed:15474312, PubMed:19357133). Also acts as a high-affinity ethanolamine/H+ antiporter, regulating the supply of extracellular ethanolamine (Etn) for the CDP-Etn pathway, redistribute intracellular Etn and balance the CDP-Cho and CDP-Etn arms of the Kennedy pathway (By similarity). Involved in membrane synthesis and myelin production (PubMed:15474312, PubMed:19357133).|||Membrane|||Mitochondrion outer membrane|||Specifically abundant in skeletal muscle (at protein level). http://togogenome.org/gene/10090:Myl10 ^@ http://purl.uniprot.org/uniprot/Q62082 ^@ Induction|||Miscellaneous|||Subunit|||Tissue Specificity ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains.|||Specifically expressed in precursor B- and T-lymphocytes.|||This chain binds calcium.|||Up-regulated by interleukin-7. http://togogenome.org/gene/10090:Cyp2c65 ^@ http://purl.uniprot.org/uniprot/Q148B1|||http://purl.uniprot.org/uniprot/Q9CVC8 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Rrm1 ^@ http://purl.uniprot.org/uniprot/P07742 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ribonucleoside diphosphate reductase large chain family.|||Cytoplasm|||Heterodimer of a large and a small subunit. Interacts with RRM2B. Interacts with AHCYL1 which inhibits its activity (By similarity).|||Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.|||The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.|||Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2.|||Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site, the dATP inhibition is mediated by AHCYL1 which stabilizes dATP in the site (By similarity). http://togogenome.org/gene/10090:Ak2 ^@ http://purl.uniprot.org/uniprot/Q9WTP6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adenylate kinase family. AK2 subfamily.|||Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.|||Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis.|||Mitochondrion intermembrane space|||Monomer.|||Present in the inner ear. Not detected in the vestibule at any developmental stage. Present at high level in the cochlea uniquely in the stria vascularis at postnatal day 7 but not at birth. Present within the lumen of the stria vascularis capillaries. Not detected in the capillaries or vessels of the adjacent connective tissue (at protein level). http://togogenome.org/gene/10090:Ccl22 ^@ http://purl.uniprot.org/uniprot/O88430|||http://purl.uniprot.org/uniprot/Q546S6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic for activated T-lymphocytes. May play an important role in the collaboration of dendritic cells and B-lymphocytes with T-cells in immune responses.|||Expressed by activated splenic B-lymphocytes and dendritic cells. Low expression in lung, thymocytes, lymph node, and unstimulated splenic cells.|||Secreted http://togogenome.org/gene/10090:Kif18a ^@ http://purl.uniprot.org/uniprot/Q91WD7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Cytoplasm|||Glycosylated.|||Interacts with CENPE and ESR1.|||Microtubule-depolymerizing kinesin which plays a role in chromosome congression by reducing the amplitude of preanaphase oscillations and slowing poleward movement during anaphase, thus suppressing chromosome movements. May stabilize the CENPE-BUB1B complex at the kinetochores during early mitosis and maintains CENPE levels at kinetochores during chromosome congression (By similarity).|||Nucleus|||Ubiquitinated.|||centrosome|||ruffle http://togogenome.org/gene/10090:Eci3 ^@ http://purl.uniprot.org/uniprot/Q78JN3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||Catalyzes the isomerization of trans-3-nonenoyl-CoA into trans-2-nonenoyl-CoA (PubMed:24344334). May also have activity towards other enoyl-CoA species (Probable).|||Expressed at high levels in the kidney. Also detected at very low levels in the duodenum, jejunum, ileum, heart, liver, lung, and brown adipose tissue (at protein level). In the kidney, expression seems to be localized mainly to the proximal tubule.|||Peroxisome|||The ACB (acyl-CoA-binding) domain is truncated and may be non-functional. http://togogenome.org/gene/10090:Polq ^@ http://purl.uniprot.org/uniprot/Q8CGS6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-A family.|||Chromosome|||DNA polymerase that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery triggered in response to double-strand breaks in DNA. MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation (PubMed:25275444, PubMed:25642963). POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). POLQ-mediated MMEJ may be required to promote the survival of cells with a compromised HR repair pathway, thereby preventing genomic havoc by resolving unrepaired lesions (PubMed:25642963). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs. It then extends each strand from the base-paired region using the opposing overhang as a template. Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ. The polymerase activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates. Also exhibits low-fidelity DNA synthesis, translesion synthesis and lyase activity, and it is implicated in interstrand-cross-link repair, base excision repair and DNA end-joining (By similarity). Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs (PubMed:16222339, PubMed:16172387, PubMed:16890500, PubMed:17449470). However, POLQ does not play a major role in somatic hypermutation (PubMed:18485835).|||Homomultimer; forms dimers and multimers. Interacts with RAD51. Interacts with ORC2 and ORC4.|||Mice develop normally, but show elevated frequencies of spontaneous and radiation-induced micronuclei, due to an increased frequency of chromosomal breakage (PubMed:12663541, PubMed:15542845, PubMed:19630521). Mice display a 20% reduction of both A/T and C/G mutations during somatic hypermutation of immunoglobulin genes (PubMed:17449470). Mice lacking both Polh and Polq do not show a further decrease of A/T mutations as compared with mice lacking only Polh (PubMed:17449470). Mice lacking both Fancd2 and Polq die during embryogenesis (PubMed:25642960).|||Nucleus|||The loop 2 region is involved in the binding of the 2 ends of resected double-strand breaks and homomultimerization. http://togogenome.org/gene/10090:Prl7d1 ^@ http://purl.uniprot.org/uniprot/P04769|||http://purl.uniprot.org/uniprot/Q5SVM4|||http://purl.uniprot.org/uniprot/Q9DAY8 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||PRP mRNA levels are highest in the fetal part of the placenta and peak at day 12 of gestation, decreasing gradually until term.|||Secreted http://togogenome.org/gene/10090:Nrxn1 ^@ http://purl.uniprot.org/uniprot/A0A0H2UH29|||http://purl.uniprot.org/uniprot/E0CY11|||http://purl.uniprot.org/uniprot/E0CZA5|||http://purl.uniprot.org/uniprot/G3UWQ9|||http://purl.uniprot.org/uniprot/P0DI97|||http://purl.uniprot.org/uniprot/Q9CS84 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the neurexin family.|||Cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N-terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)-triggered exocytosis of secretory granules in pituitary gland. They may affect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latrotoxin from spider venom.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN1 forming a heterotetramer, where one NLGN1 dimer interacts with one NRXN1 dimer (PubMed:18334216, PubMed:20624592). Also interacts (via laminin G-like domain 2 and/or laminin G-like domain 6) with NLGN2, NLGN3 and NLGN4L; interactions with NLGN1, NLGN2, NLGN3 and NLGN4L are calcium-dependent (PubMed:18434543, PubMed:20624592). Interacts (via cytoplasmic C-terminal region) with CASK (via the PDZ, SH3 and guanylate kinase-like domains) (PubMed:25385611). Interacts (via cytoplasmic C-terminus) with CASKIN1 and APBA1 (By similarity). Interacts (via laminin G-like domain 2) with NXPH1 and NXPH3 (By similarity). Alpha-type isoforms (neurexin-1-alpha) interact (via laminin G-like domain 2 and/or laminin G-like domain 6) with DAG1 (via alpha-dystroglycan chain) (By similarity). Interacts with LRRTM1, LRRTM2, LRRTM3 and LRRTM4 (By similarity). Interacts with SYT13 and SYTL1 (PubMed:11243866, PubMed:11171101). Interacts with CBLN1, CBLN2 and, less avidly, with CBLN4 (PubMed:21410790). Interacts with CLSTN3 (PubMed:24094106, PubMed:24613359, PubMed:32434929).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Neuronal cell surface protein involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins (By similarity). Plays a role in formation of synaptic junctions (PubMed:30100184).|||No visible phenotype, but mice display subtle behavorial deficits. Females show deficits in nest building and taking care of pups. Mice lacking the alpha-type isoforms of NRXN1, NRXN2 and NRXN3 are born at the expected Mendelian rate, but die during the first day after birth, probably due to neurological defects in the brainstem that impair normal breathing. These mice express normal levels of the beta-type isoforms of NRXN1, NRXN2 and NRXN3. Mice show reduced density of synapses in the brainstem, especially a reduction in the numbers of GABA-releasing synapses. Their brains display a reduced frequency of spontaneous neurotransmitter release, and decreased neurotransmitter release in response to an action potential. Likewise, the activity of voltage-gated calcium channels is strongly decreased. A small proportion (5-10%) of mice lacking the alpha-type isoforms of both NRXN1 and NRXN2 survive to adulthood; these mice do not show any gross anatomical defects in their brains or changes in the distribution of synaptic proteins, but they have fewer synapses in the neocortex and show defects in neurotransmitter release at neuromuscular junctions.|||O-glycosylated; contains heparan sulfate. Heparan sulfate attachment is required for synapse development by mediating interactions with neuroligins and LRRTM2.|||O-glycosylated; contains heparan sulfate. Heparan sulfate attachment is required for synapse development by mediating interactions with neuroligins.|||Presynaptic cell membrane|||Produced by alternative promoter usage and alternative splicing.|||The cytoplasmic C-terminal region binds to CASK. Binds NLGN1, NLGN2 and NLGN3, DAG1 (alpha-dystroglycan) and alpha-latrotoxin. Binding to neuroligins is calcium-dependent, and the binding preference ranks as follow: NLGN1 > NLGN4 >> NLGN3 > NLGN2 (By similarity). Interacts with CBLN2 and more weakly with CBLN4 (PubMed:22220752, PubMed:29782851). Interacts with CBLN1; interaction is CBLN1 hexamer form-dependent; CBLN1-binding is calcium-independent; isoform 1b does not interact with CBLN1 (PubMed:21410790, PubMed:22220752, PubMed:29782851). Interacts with CLSTN3 (PubMed:24613359, PubMed:32434929). http://togogenome.org/gene/10090:Ppm1h ^@ http://purl.uniprot.org/uniprot/Q3UYC0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PP2C family.|||Cytoplasm|||Dephosphorylates CDKN1B at 'Thr-187', thus removing a signal for proteasomal degradation.|||Nucleus http://togogenome.org/gene/10090:Fzd6 ^@ http://purl.uniprot.org/uniprot/Q3UTZ0|||http://purl.uniprot.org/uniprot/Q542J1|||http://purl.uniprot.org/uniprot/Q61089 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Cell surface|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Expressed in both hair cells and supporting cells in the utricle, saccule, cristae and the organ of Corti in the inner ear (at protein level).|||Half of the males without the gene, but not females, display abnormal claw morphology or absent claws compared to wild-type; at the age of 2 to 3 months, the claws disappear or become rudimentary on the hind limbs (PubMed:21665003). FZD3 and FZD6 double knockout embryos have a curled tail, exhibit defects in neural tube and eyelids closure, in the orientation of hair bundles on inner-ear sensory cells and die at birth (PubMed:16495441).|||Interacts with LMBR1L.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (By similarity). Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear.|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Amy2a4 ^@ http://purl.uniprot.org/uniprot/P00688 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 13 family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 1 Cl(-) ion per subunit.|||Monomer.|||extracellular space http://togogenome.org/gene/10090:Sik1 ^@ http://purl.uniprot.org/uniprot/Q60670 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-182. Also activated by phosphorylation on Thr-322 in response to increases in intracellular sodium in parallel with elevations in intracellular calcium through the reversible sodium/calcium exchanger.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily.|||Cytoplasm|||Expressed in lung, skin, ovary, heart and stomach. No expression in brain, liver or adult skeletal muscle but is present in skeletal muscle progenitor cells of the somite beginning at 9.5 dpc. Present at 8.0 dpc in the monolayer of presumptive myocardial cells but rapidly down-regulated at 8.5 dpc upon primitive ventricle formation, although still present in myocardial cells that will populate the primitive atrium and bulbus cordis. At 9.5 dpc expression is down-regulated in the primitive atrium but observed in the sinus venosus and truncus arteriosus.|||Expression is stimulated by CREB1 in myocytes; direct target of CREB1.|||Interacts (when phosphorylated on Thr-182 and Ser-186) with YWHAZ. Interacts with ATP1A1 (By similarity).|||Nucleus|||Phosphorylated at Thr-182 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39, leading to its activation. Phosphorylation at Thr-182 promotes autophosphorylation at Ser-186, which is required for sustained activity. Autophosphorylation at Ser-186 is maintained by sequential phosphorylation at Thr-182 by GSK3-beta. GSK3-beta cannot initiate phosphorylation at Thr-182, it can only maintain it. Phosphorylation at Ser-577 by PKA promotes translocation to the cytoplasm. Phosphorylation at Thr-322 by CaMK1 following intracellular sodium concentration leads to activation.|||Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1 and CRTC2/TORC2. Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1.|||The RK-rich region determines the subcellular location. http://togogenome.org/gene/10090:Setdb2 ^@ http://purl.uniprot.org/uniprot/B2RXP3 ^@ Subcellular Location Annotation ^@ Chromosome http://togogenome.org/gene/10090:Tpmt ^@ http://purl.uniprot.org/uniprot/A0A0R4J018|||http://purl.uniprot.org/uniprot/O55060 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.|||Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) using S-adenosyl-L-methionine as the methyl donor (PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Nek9 ^@ http://purl.uniprot.org/uniprot/Q69Z43|||http://purl.uniprot.org/uniprot/Q8K1R7 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated during mitosis by intramolecular autophosphorylation. Activity and autophosphorylation is activated by manganese >> magnesium ions. It is not cell-cycle regulated but activity is higher in G0-arrested cells.|||Autophosphorylated on serine and threonine residues. When complexed with FACT, exhibits markedly elevated phosphorylation on Thr-210. During mitosis, not phosphorylated on Thr-210. Phosphorylated by CDK1 in vitro.|||Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Cytoplasm|||Dimerizes through its coiled-coil domain.|||Homodimer; homodimerization is required to activate NEK7. Binds to Ran GTPase. Has a greater affinity for Ran-GDP over Ran-GTP. Interacts with SSRP1 and SUPT16H, the 2 subunits of the FACT complex. Interacts with DYNLL1; phosphorylation at Ser-949 strongly reduces DYNLL1 binding.|||Nucleus|||Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation. Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2. Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues. Important for G1/S transition and S phase progression. Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively. http://togogenome.org/gene/10090:Zbtb5 ^@ http://purl.uniprot.org/uniprot/Q7TQG0 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Lrrc17 ^@ http://purl.uniprot.org/uniprot/Q9CXD9 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Down-regulated in osteoblasts in response to pro-osteoclastogenic factors.|||Expressed in osteoblasts, spleen, lung and heart.|||Involved in bone homeostasis. Acts as a negative regulator of RANKL-induced osteoclast precursor differentiation from bone marrow precursors.|||extracellular space http://togogenome.org/gene/10090:Gadd45gip1 ^@ http://purl.uniprot.org/uniprot/Q9CR59 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occurs also in the absence of GADD45 proteins. Acts as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity. May be involved in the hormone-mediated regulation of NR4A1 transcriptional activity. May play a role in mitochondrial protein synthesis.|||Belongs to the mitochondrion-specific ribosomal protein mL64 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Interacts with GADD45A, GADD45B and GADD45G. Interacts with NR4A1 via the NR4A1 AB domain. Interacts with ATAD3A and ATAD3B.|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Acad12 ^@ http://purl.uniprot.org/uniprot/D3Z7X0 ^@ Similarity ^@ Belongs to the acyl-CoA dehydrogenase family. http://togogenome.org/gene/10090:Mepe ^@ http://purl.uniprot.org/uniprot/Q8K4L6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PF07175/osteoregulin family.|||Cleaved by CTSB/cathepsin B; the cleavage is blocked by metalloprotease PHEX.|||Detected at 16 days post coitum (dpc) in both epithelial and mesenchymal components of the tooth organ (PubMed:26927967). Also detected at 16 dpc and 18 dpc in mandibular bone osteocytes (PubMed:26428891). Detected at 15 dpc in the bone collar (PubMed:26428891). Detected at 13 dpc in the cartilage matrix (PubMed:26428891). Detected at postnatal day 3 in odontoblasts and ameloblasts (PubMed:22042093). At postnatal day 5, expression is decreased in dental papilla cells, but increased in the predentin (PubMed:22042093). By postnatal day 9, is only detected in the predentin (PubMed:22042093). Detected at postnatal day 2 in osteoblasts, the calcified cartilage cores in primary metaphyseal bone and in osterocytes embedded in cortical bone matrix (PubMed:15221418). At postnatal day 84 expression is detected in the osteocytes of cortical and trabecular bone (PubMed:15221418).|||Expressed in osteocytes (at protein level) (PubMed:12421822, PubMed:15221418). Expressed by chondrocytes, specifically in the hypertrophic zone of the bone growth plate (at protein level) (PubMed:22766095). Expressed in osteoblasts in bone (at protein level) (PubMed:11414762, PubMed:15221418, PubMed:18597632). Expressed by osteoblasts within the metaphysis (at protein level) (PubMed:15221418, PubMed:22766095). Expressed at low levels in white fat, brown fat, testes, brain and aorta (PubMed:12421822). Expressed in the craniofacial complex (at protein level) (PubMed:26927967). Expressed in odontoblasts, ameloblasts and in predentin during tooth development (at protein level) (PubMed:22042093). Expressed in the kidney (at protein level) (PubMed:26051469). Expressed in osteocytes in mandibular condylar cartilage and tibial cartilage (at protein level) (PubMed:26428891). Expressed in salivary glands (PubMed:15329369).|||Induced by ascorbate and beta-glycerophosphate (PubMed:11414762, PubMed:12421822). Induced expression during bone fracture healing, with low levels of expression being detected in fibroblast-like cells at 6 days post-fracture, and increased expression at 10 days post-fracture in late hypertrophic chondrocytes. At 14 days post-fracture, expression is detected in osteocytes, osteoblasts, and hypertrophic chondrocytes. By 28 days post-fracture, expression was highest in osteocytes and lower in osteoblasts (PubMed:15221418). Down-regulated by 1-alpha-25-dihydroxyvitamin D3 (calcitriol) (PubMed:11414762).|||Interacts (via ASARM motif) with PHEX; the interaction is zinc-dependent.|||It has been proposed that MEPE is cleaved and generate 2 peptides dentonin and ASARM peptide.|||Mutant mice exhibit increased cancellous bone mass and no loss of trabecular bone characteristics (PubMed:12421822, PubMed:26051469). They also exhibit decreased biomechanical strength in their bones and increased skeletal mineralization (PubMed:15843468). In craniofacial complex development, mutant mice also exhibit hypermineralization in predentin, dentin and enamel of teeth and decreased expression of AMBN, ENAM, IBSP, DMP1, DSPP and SPP1 (PubMed:26927967). Mutant mice also exhibit hyperphostatemia and increased expression of SLC34A1/NPT2a, SLC34A3/NPT2c and VEGF in the kidney (PubMed:26051469). Hyperuricemia and reduced fractional excretion of uric acid was also exhibited (PubMed:26051469). As mutant mice age, bone mineral density and content is increased (PubMed:26051469).|||Phosphorylated on serine residues in the ASARM motif; the phosphorylation is important for the inhibition of bone mineralization.|||Regulates renal phosphate and uric acid excretion (PubMed:26051469). Regulates bone mineralization by osteoblasts and cartilage mineralization by chondrocytes (PubMed:11414762, PubMed:12421822, PubMed:15843468, PubMed:22766095). Regulates the mineralization of the extracellular matrix of the craniofacial complex, such as teeth, bone and cartilage (PubMed:26927967). Increases dental pulp stem cell proliferation (By similarity).|||The acidic serine aspartate-rich MEPE-associated (ASARM) motif is sufficient when phosphorylated to inhibit bone mineralization by osteoblasts and cartilage mineralization by chondrocytes by binding hydroxyapatite crystals during the mineralization stage (PubMed:15843468, PubMed:22766095, PubMed:26051469). It can also inhibit dentin mineralization (By similarity).|||The dentonin region is sufficient to promote dental pulp stem cell proliferation. It can also stimulate bone formation, osteoblast differentiation, and activate integrin signaling pathways.|||extracellular matrix http://togogenome.org/gene/10090:Epx ^@ http://purl.uniprot.org/uniprot/P49290 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxidase family. XPO subfamily.|||Binds 1 Ca(2+) ion per heterodimer.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.|||Cytoplasmic granule|||Mediates tyrosine nitration of secondary granule proteins in mature resting eosinophils.|||Tetramer of two light chains and two heavy chains. http://togogenome.org/gene/10090:Pkd2l2 ^@ http://purl.uniprot.org/uniprot/Q3V056|||http://purl.uniprot.org/uniprot/Q9JLG4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the polycystin family.|||Expressed only in testis and heart.|||May function as a subunit of a cation channel and play a role in fertilization.|||Membrane http://togogenome.org/gene/10090:Rgs9 ^@ http://purl.uniprot.org/uniprot/O54828|||http://purl.uniprot.org/uniprot/Q3UUR0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Heterodimer with GNB5. Interacts with RGS7BP, leading to regulate the subcellular location of the heterodimer formed with GNB5 (PubMed:15632198, PubMed:15897264). Component of the RGS9-1-Gbeta5 complex composed of RGS9 (RGS9-1), Gbeta5 (GNB5) and RGS9BP (PubMed:12119397, PubMed:12499365, PubMed:14614075, PubMed:16908407). Interacts with PDE6G and GNAT1 (By similarity).|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to GNAT1. Involved in phototransduction; key element in the recovery phase of visual transduction.|||Isoform 1 is expressed in photoreceptor outer segments. Isoform 2 is expressed in brain striatum.|||Membrane|||Retinal isoform 1 is light-dependent phosphorylated at 'Ser-475'. Phosphorylation is decreased by light exposition. Interaction with RGS9BP is decreased when isoform 1 is phosphorylated at 'Ser-475'. http://togogenome.org/gene/10090:Mss51 ^@ http://purl.uniprot.org/uniprot/Q9D5Z5 ^@ Caution ^@ Although no clear MSS51 ortholog is encoded in mammalian genomes, the mammalian MSS51/ZMYND17 protein is significantly similar. Considered by a number of resources to be the ortholog of yeast MSS51. http://togogenome.org/gene/10090:Garin3 ^@ http://purl.uniprot.org/uniprot/Q5STT6 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GARIN family.|||Cajal body|||Expressed in adult spermatocytes and spermatids.|||Golgi apparatus|||Interacts (via N-terminus) with RAB2B (in GTP-bound form) (PubMed:18256213). Interacts with FRG1.|||It is uncertain whether Met-1 or Met-8 is the initiator.|||May be involved in RNA biogenesis. http://togogenome.org/gene/10090:Igf1 ^@ http://purl.uniprot.org/uniprot/E9PU89|||http://purl.uniprot.org/uniprot/E9Q138|||http://purl.uniprot.org/uniprot/P05017|||http://purl.uniprot.org/uniprot/Q4VJB9|||http://purl.uniprot.org/uniprot/Q4VJC0|||http://purl.uniprot.org/uniprot/Q8CAR0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the insulin family.|||Expression in the bone oscillates in a circadian manner and its expression is negatively regulated by CCRN4L/NOC.|||Forms a ternary complex with IGFR1 and ITGAV:ITGB3. Forms a ternary complex with IGFR1 and ITGA6:ITGB4. Interacts with SH2D3C isoform 2 (PubMed:20881139).|||Secreted|||The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (By similarity). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (PubMed:21496647). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiatiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (By similarity). http://togogenome.org/gene/10090:Utp14a ^@ http://purl.uniprot.org/uniprot/Q640M1 ^@ Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UTP14 family.|||Citrullinated by PADI4.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with DHX37.|||May be required for ribosome biogenesis.|||The mouse genome also contains the Utp14b gene, an autosomal retrotransposed copy of this X-linked gene. Evolution of autosomal retrogenes from X-linked progenitors compensates for X-chromosome silencing during male meiosis.|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Creb1 ^@ http://purl.uniprot.org/uniprot/Q01147|||http://purl.uniprot.org/uniprot/Q543W0|||http://purl.uniprot.org/uniprot/Q547S9|||http://purl.uniprot.org/uniprot/Q62347 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family.|||Expressed in the heart (at protein level).|||Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3. Interacts (phosphorylated form) with TOX3 (By similarity). When phosphorylated on Ser-119, binds CREBBP. Interacts with ARRB1. Binds to HIPK2 (By similarity). Interacts with SGK1 (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119 (By similarity). Forms a complex with KMT2A and CREBBP (By similarity). Interacts with TOX4; CREB1 is required for full induction of TOX4-dependent activity and the interaction is increased by cAMP and inhibited by insulin (PubMed:34914893).|||Nucleus|||Phosphorylation of Ser-119 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylated Ser-128 can be detected in the suprachiasmatic nucleus (SCN), the amygdala, the cortex, and the hippocampus but not in the striatum nor in the cerebellum. In the SCN, phosphorylation of Ser-128 and Ser-119 are stimulated by light exposure and submitted to circadian oscillations. In the retina, only phosphorylation of Ser-119 can be detected upon light exposure. Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119. CaMK4 is much more potent than CAMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-128. Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP (By similarity). Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. Phosphorylated by TSSK4 on Ser-119 (By similarity).|||Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity). Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (By similarity). Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (PubMed:11970866, PubMed:21728997). Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (PubMed:30566056).|||Sumoylated with SUMO1. Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization (By similarity). http://togogenome.org/gene/10090:Amh ^@ http://purl.uniprot.org/uniprot/A0A8Q0P8A2|||http://purl.uniprot.org/uniprot/P27106 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Expressed in Sertoli cells of fetal testes, and in testes just after birth, but absent in adult testes. In female, AMH is expressed after birth in the granulosa cells of the follicle.|||Homodimer; disulfide-linked.|||Homozygous null mutant males have a complete male reproductive tract and functional sperm, but also uterus and oviducts (PubMed:7954809). Most are infertile due to female organs blocking sperm transfer. Females are fertile with enlarged ovaries and atypical follicles (PubMed:7954809). Furthemore in the absence of AMH, follicle growth is more sensitive to stimulation by FSH (PubMed:11606457).|||Plays an important role in several reproductive functions, including Muellerian duct regression during male fetal sexua,l differentiation and in the adult plays a role in Leydig cell differentiation and function (PubMed:1782869, PubMed:9435237). In female acts as a negative regulator of the primordial to primary follicle transition and decreases FSH sensitivity of growing follicles (PubMed:11861535, PubMed:11606457). Binds to its sole type II receptor, AMHR2 that recruits type I receptors ACVR1 and BMPR1A which subsequently activates the Smad pathway (By similarity).|||Plays an important role in several reproductive functions. Induces Muellerian duct regression during male fetal sexual differentiation and plays a role in Leydig cell differentiation and function. In female acts as a negative regulator of the primordial to primary follicle transition and decreases FSH sensitivity of growing follicles. AMH signals by binding to a specific type-II receptor, AMHR2, that heterodimerizes with type-I receptors (ACVR1 and BMPR1A), and recruiting SMAD proteins that are translocated to the nucleus to regulate target gene expression.|||Preproprotein is proteolytically processed to generate N- and C-terminal cleavage products that homodimerize and associate to form a biologically active non-covalent complex. Binding of the non-covalent complex to AMHRII induces dissociation of the pro-region from the mature C-terminal dimer. The N-terminal portion of the protein, despite having no intrinsic activity, has the role of amplifying the activity of the C-terminus.|||Secreted http://togogenome.org/gene/10090:Cldn17 ^@ http://purl.uniprot.org/uniprot/Q8BXA6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Cell membrane|||Channel-forming tight junction protein with selectivity for anions, including chloride and bicarbonate, and for solutes smaller than 9 Angstrom in diameter. In the kidney proximal tubule, may be involved in quantitative reabsorption of filtered anions. Does not affect water permeability.|||Expressed at high levels in the kidney and at mucher lower levels in the brain. In the kidney, expression gradually decreases from the proximal tubule downstream to the distal convoluted tubule. Expressed in the thin ascending limb of Henle's loop, as well as in the thick ascending limb of Henle's loop. In the distal convoluted tubules, expressed only in a few tubules. Not detected in the collecting duct. In the brain, expressed in blood vessels (at protein level).|||Interacts with OCLN.|||tight junction http://togogenome.org/gene/10090:Ptcd2 ^@ http://purl.uniprot.org/uniprot/Q8R3K3 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PTCD2 family.|||Contaminating sequence. Potential vector sequence.|||Deficient mice shown deficiency of the third complex of the respiratory chain that caused profound ultrastructural changes in the heart. The outer layers of ventricular cardiomyocytes appeared to be infiltrated with macrovesicular fat deposits, having the appearance of adipocytes.|||High expression in heart and liver and low expression in kidney, brain and testis.|||Involved in mitochondrial RNA maturation and mitochondrial respiratory chain function.|||Mitochondrion http://togogenome.org/gene/10090:Col1a2 ^@ http://purl.uniprot.org/uniprot/Q01149 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibrillar collagen family.|||Expressed in kidney glomeruli.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function.|||Trimers of one alpha 2(I) and two alpha 1(I) chains.|||Type I collagen is a member of group I collagen (fibrillar forming collagen).|||extracellular matrix http://togogenome.org/gene/10090:Layn ^@ http://purl.uniprot.org/uniprot/Q8C351 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with TLN1 (By similarity). Interacts with NF2 and RDX.|||Membrane|||Receptor for hyaluronate.|||The C-terminal domain interacts with the N-terminal domain of RDX. http://togogenome.org/gene/10090:Mgst3 ^@ http://purl.uniprot.org/uniprot/Q9CPU4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MAPEG family.|||Displays both glutathione S-transferase and glutathione peroxidase activities toward oxyeicosanoids. Catalyzes the Michael addition reaction of reduced glutathione (GSH) to electrophilic eicosanoids to form GSH adducts, as part of detoxification or metabolic shunt processes. Mediates GSH conjugation to leukotriene A4 to form the sulfidopeptide leukotriene C4. Metabolizes cyclopentenone prostanoids, specifically mediates GSH addition at C9 within the cyclopentenone ring of 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2) to form 15dPGJ2-glutathione. L-cysteine can not substitute for GSH. Catalyzes the reduction of eicosanoid peroxides to yield eicosanoid hydroxides.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Or2v1 ^@ http://purl.uniprot.org/uniprot/Q8VGD6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. Activated by (+) and (-)-limonene. http://togogenome.org/gene/10090:Srd5a2 ^@ http://purl.uniprot.org/uniprot/Q99N99 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the steroid 5-alpha reductase family.|||Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Pmel ^@ http://purl.uniprot.org/uniprot/Q60696 ^@ Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMEL/NMB family.|||Defects in Silver mutants are the cause of the silver coat color which seems to be due to premature death of pigment cells during the hair cycle.|||Endoplasmic reticulum membrane|||Expressed in skin melanocytes, choroid melanocytes, and retinal pigmented cells.|||Extracellular vesicle|||Forms physiological amyloids that play a central role in melanosome morphogenesis and pigmentation. The maturation of unpigmented premelanosomes from stage I to II is marked by assembly of processed amyloidogenic fragments into parallel fibrillar sheets, which elongate the vesicle into a striated ellipsoidal shape. In pigmented stage III and IV melanosomes, the amyloid matrix serves as a platform where eumelanin precursors accumulate at high local concentrations for pigment formation. May prevent pigmentation-associated toxicity by sequestering toxic reaction intermediates of eumelanin biosynthesis pathway.|||Homodimer; disulfide-linked. Dimerization in the endoplasmic reticulum and early Golgi prevents premature fibril formation. The dimers are resolved to monomers in late- or post-Golgi compartments. Heterooligomer; amyloid-type. Processed amyloidogenic fragments assemble into fibrils that further organize into beta-sheet quaternary amyloid structures. Interacts (via luminal C-terminal fragment) with CD63; this is important for sorting of the luminal fragment in tetraspanin rich microdomains in stage I melanosomes to prevent premature lysosomal degradation. Interacts with APOE; this allows the loading of the luminal fragment on ILVs to induce fibril nucleation. Interacts with MLANA.|||Melanosome|||Mutant mice are fertile and have normal development. They display coat color dilution phenotype especially in the brown background. This is associated with abnormal melanogenesis characterized by spherical melanosomes and substantial reduction in eumelanin content in hair.|||N- and O-glycosylated. A small amount of P1/P100 (major form) undergoes glycosylation in ER and Golgi compartments to yield P2/P120 (minor form). The mature P2 form leaves the trans-Golgi network and is mainly targeted to stage I melanosomes via the plasma membrane and clathrin-mediated endocytosis. Stage II melanosomes harbor only Golgi-modified fragments that are derived from M-alpha and that bear sialylated O-linked oligosaccharides. O-glycosylation of the RPT region is a conserved feature likely involved in amyloid sheet separation via electrostatic repulsion.|||Secreted|||The Kringle-like domain (KLD) contains six highly conserved cysteine residues that are critical for dimer formation.|||The core amyloid fragment (CAF) represents the amyloidogenic unit of melanosomal fibrils.|||The highly O-glycosylated repeat (RPT) domain drives the generation of the fibrillar amyloid sheet structures within melanosomes. The O-glycosylation sites rather than its primary amino acid sequence are conserved across species.|||Undergoes multiple proteolytic processing. In a post-Golgi prelysosomal compartment, P2 is cleaved by a furin-like proprotein convertase (PC) into two disulfide-linked subunits: a large lumenal subunit, M-alpha/ME20-S, and an integral membrane subunit, M-beta. Despite cleavage, only a small fraction of M-alpha is secreted, as most M-alpha and M-beta remain associated with each other intracellularly via a disulfide bond. Once targeted to stage I melanosomes, beta-secretase BACE2 cleaves the M-beta fragment to release the amyloidogenic luminal fragment containing M-alpha and a small portion of M-beta N-terminus. M-alpha is further cleaved by metalloproteases and still unknown proteases to yield subfragments that ultimately assemble into amyloid fibrils. The C-terminal fragment of M-beta is processed by the gamma-secretase complex to release a short intracytoplasmic domain.|||cis-Golgi network membrane|||multivesicular body http://togogenome.org/gene/10090:Kdm2b ^@ http://purl.uniprot.org/uniprot/Q6P1G2 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JHDM1 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Chromosome|||Histone demethylase activity is inhibited by fumarate.|||Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (By similarity). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (By similarity).|||Interacts with SKP1, forming heterodimers (By similarity). The KDM2B-SKP1 heterodimeric complex interacts with the PCGF1-BCORL heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (By similarity). Directly interacts with CUL1. The SKP1-KDM2B interacts with UBB (By similarity).|||Nucleus|||The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides.|||The F-box domain mediates interaction with UBB.|||The JmjC domain mediates demethylation activity (By similarity). It is also required for repression of ribosomal RNA genes (By similarity).|||The LRR repeats are required for the interaction with the PCGF1-BCORL1 heterodimeric complex.|||nucleolus http://togogenome.org/gene/10090:Hbb-bs ^@ http://purl.uniprot.org/uniprot/A8DUK4|||http://purl.uniprot.org/uniprot/P02088 ^@ Function|||Miscellaneous|||Polymorphism|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the globin family.|||Heterotetramer of two alpha chains and two beta chains.|||Inbred mouse strains possess 1 of 4 alleles at the HBB locus: D (diffuse), S (single), P and W1. The D and P alleles are actually closely linked doublets that coordinately express a major and a minor chain, the minor chain being slightly different in the two alleles. The S allele produces only 1 chain, it is characteristic of North American wild mice. The W1 allele is observed mainly in Northwestern China.|||Involved in oxygen transport from the lung to the various peripheral tissues.|||Red blood cells.|||The D-major sequence is shown. See also the entry for the beta D and P-minor chain. http://togogenome.org/gene/10090:Arhgap30 ^@ http://purl.uniprot.org/uniprot/Q640N3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle|||GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42.|||Interacts with RHOU in a GTP-independent manner. http://togogenome.org/gene/10090:Lipo2 ^@ http://purl.uniprot.org/uniprot/D3YY49 ^@ Similarity ^@ Belongs to the AB hydrolase superfamily. Lipase family. http://togogenome.org/gene/10090:Casp8 ^@ http://purl.uniprot.org/uniprot/A0A087WQT6|||http://purl.uniprot.org/uniprot/O89110|||http://purl.uniprot.org/uniprot/Q3U607 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Inhibited by baculovirus p35 protein P35.|||(Microbial infection) Proteolytically cleaved by the cowpox virus CRMA death inhibitory protein.|||Belongs to the peptidase C14A family.|||CASP8 activity is restricted by RIPK1.|||Cytoplasm|||Embryonic lethality at lethality at 10.5 dpc (PubMed:9729047). Embryos display impaired heart muscle development and congested accumulation of erythrocytes (PubMed:9729047). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Casp8; mice however die the first days of postnatal life (PubMed:24813849). Only mice lacking Ripk1, Ripk3 and Casp8 survive past weaning and rescue lethality caused by the absence of Ripk1 (PubMed:24813849, PubMed:24813850).|||Expressed in a wide variety of tissues. Highest expression in spleen, thymus, lung, liver and kidney. Lower expression in heart, brain, testis and skeletal muscle.|||Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease (PubMed:31511692). GZMB and CASP10 can be involved in these processing events (By similarity).|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit (By similarity). Interacts with CFLAR and PEA15 (By similarity). Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (By similarity). Interacts with TNFAIP8L2 (PubMed:18455983). Interacts with CASP8AP2 (PubMed:17245429). Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15383280). Interacts with UBR2 (By similarity). Interacts with RIPK1 (PubMed:31519887). Interacts with FADD (PubMed:29440439). Interacts with stimulated TNFRSF10B; this interaction is followed by CASP8 proteolytic cleavage and activation (By similarity). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287).|||In the embryo, highest expression occurs at day 7.|||Nucleus|||Phosphorylation on Ser-389 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (By similarity).|||Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:12065591, PubMed:18455983, PubMed:30361383, PubMed:30381458, PubMed:31511692, PubMed:31748744, PubMed:33397971). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed:9654089, PubMed:9837723, PubMed:24813849, PubMed:24813850). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (By similarity). Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A (PubMed:29440439). The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (By similarity). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (By similarity). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (By similarity). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-325', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31511692). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:30361383, PubMed:30381458). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (PubMed:30361383, PubMed:30381458). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (PubMed:32971525). May participate in the Granzyme B (GZMB) cell death pathways (By similarity). Cleaves PARP1 and PARP2 (PubMed:12065591). http://togogenome.org/gene/10090:Fbxw11 ^@ http://purl.uniprot.org/uniprot/Q5SRY7 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expression is negatively regulated by Wnt/beta-catenin pathway.|||Nucleus|||Self-associates (By similarity). Component of the SCF(FBXW11) complex formed of CUL1, SKP1, RBX1 and a FBXW11 dimer (PubMed:11896578). Interacts with BST2 and USP47 (By similarity). Interacts with TRIM21 (By similarity). Interacts with PER3 (PubMed:15917222). Interacts with INAVA (By similarity). Interacts with REST (By similarity).|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11896578). Probably recognizes and binds to phosphorylated target proteins: the interaction with substrates requires the phosphorylation of the two serine residues in the substrates' destruction motif D-S-G-X(2,3,4)-S (By similarity). SCF(FBXW11) mediates the ubiquitination of phosphorylated CTNNB1 and participates in Wnt signaling regulation (By similarity). SCF(FBXW11) plays a key role in NF-kappa-B activation by mediating ubiquitination of phosphorylated NFKBIA, leading to its degradation by the proteasome, thereby allowing the associated NF-kappa-B complex to translocate into the nucleus and to activate transcription (PubMed:11896578). The SCF(FBXW11) complex also regulates NF-kappa-B by mediating ubiquitination of phosphorylated NFKB1: specifically ubiquitinates the p105 form of NFKB1, leading to its degradation (By similarity). SCF(FBXW11) mediates the ubiquitination of IFNAR1 (By similarity). SCF(FBXW11) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (By similarity). Involved in the oxidative stress-induced a ubiquitin-mediated decrease in RCAN1 (By similarity). Mediates the degradation of CDC25A induced by ionizing radiation in cells progressing through S phase and thus may function in the intra-S-phase checkpoint (By similarity). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and phosphorylated PER2 (PubMed:18782782). SCF(FBXW11) mediates the ubiquitination of CYTH1, and probably CYTH2 (By similarity). SCF(FBXW11) acts as a regulator of mTORC1 signaling pathway by catalyzing ubiquitination and subsequent proteasomal degradation of phosphorylated DEPTOR, TFE3 and MITF (By similarity).|||The N-terminal D domain mediates homodimerization. http://togogenome.org/gene/10090:Proz ^@ http://purl.uniprot.org/uniprot/Q9CQW3 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although homologous with the vitamin K-dependent clotting factors, it has lost two of the essential catalytic residues and has no enzymatic activity.|||Appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. Inhibits activity of the coagulation protease factor Xa in the presence of SERPINA10, calcium and phospholipids (By similarity).|||Belongs to the peptidase S1 family.|||Plasma.|||Secreted|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Apbb1ip ^@ http://purl.uniprot.org/uniprot/Q8R5A3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Appears to function in the signal transduction from Ras activation to actin cytoskeletal remodeling. Suppresses insulin-induced promoter activities through AP1 and SRE. Mediates Rap1-induced adhesion (By similarity).|||Belongs to the MRL family.|||Cell membrane|||Interacts, through the N-terminal Pro-rich region, with the WW domain of APBB1. Interacts with RAP1A, PFN1, VASP and ENAH.|||Ubiquitously expressed with high expression in the hematopoietic system.|||cytoskeleton|||focal adhesion|||lamellipodium http://togogenome.org/gene/10090:Stxbp5l ^@ http://purl.uniprot.org/uniprot/Q5DQR4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat L(2)GL family.|||Cell membrane|||Cytoplasm|||Detected in hippocampus and cerebellum (PubMed:15659226). Expressed in pancreatic beta-cells where it modulates insulin secretion (PubMed:21998599).|||Interacts with STX1A and STX4.|||Membrane|||Mutant mice are born at the expected Mendelian rate and show normal body weight development. However, they display reduced sensorimotor gating and impaired motor performance.|||Phosphorylated, leading to STXBP5L increased turnover and subsequent de-repression of insulin secretion (PubMed:25002582). Phosphorylated on serine residues in response to glucose or phorbol esters (PubMed:25002582).|||Plays a role in vesicle trafficking and exocytosis inhibition (PubMed:25002582). In pancreatic beta-cells, inhibits insulin secretion probably by interacting with and regulating STX1A and STX4, key t-SNARE proteins involved in the fusion of insulin granules to the plasma membrane (PubMed:21998599). Also plays a role in neurotransmitter release by inhibiting basal acetylcholine release from axon terminals and by preventing synaptic fatigue upon repetitive stimulation (PubMed:24744148). Promotes as well axonal outgrowth (By similarity).|||Ubiquitinated by the E3 ligase SYVN1, leading to STXBP5L proteasomal degradation. http://togogenome.org/gene/10090:Krt8 ^@ http://purl.uniprot.org/uniprot/P11679 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Expressed in abundance in the epithelia of colon, bladder, ileum, and stomach, with lower expression observed in earskin (at protein level). Also expressed in pancreas, liver, dudenum and jejunum.|||Heterotetramer of two type I and two type II keratins (PubMed:24940650). Forms a heterodimer with KRT18 (PubMed:24940650). Associates with KRT20 (PubMed:12857878). Interacts with PLEC isoform 1C, when in a heterodimer with KRT18 (PubMed:24940650). Interacts with PNN (By similarity). When associated with KRT19, interacts with DMD. Interacts with TCHP (By similarity). Interacts with APEX1 (By similarity). Interacts with GPER1 (By similarity). Interacts with EPPK1 (PubMed:25617501). Interacts with PKP1 and PKP2 (By similarity).|||Nucleus matrix|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.|||O-glycosylated. O-GlcNAcylation at multiple sites increases solubility, and decreases stability by inducing proteasomal degradation (By similarity).|||Phosphorylation on serine residues is enhanced during EGF stimulation and mitosis. Ser-80 phosphorylation plays an important role in keratin filament reorganization (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.|||nucleoplasm http://togogenome.org/gene/10090:Tmprss15 ^@ http://purl.uniprot.org/uniprot/E9Q6Y6|||http://purl.uniprot.org/uniprot/P97435|||http://purl.uniprot.org/uniprot/Q8CC97 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DMBT1 family.|||Belongs to the peptidase S1 family.|||Heterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases (By similarity).|||Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.|||The chains are derived from a single precursor that is cleaved by a trypsin-like protease. http://togogenome.org/gene/10090:D630045J12Rik ^@ http://purl.uniprot.org/uniprot/Q68FD9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UPF0606 family.|||Expressed in retina photoreceptor cells (at protein level).|||May play a role in photoreceptor function.|||Membrane|||O-glycosylated. O-mannosylated by POMT1 and POMT2 and elongated by POMGNT1.|||Probable cloning artifact.|||cilium http://togogenome.org/gene/10090:Aig1 ^@ http://purl.uniprot.org/uniprot/Q3TS32|||http://purl.uniprot.org/uniprot/Q9D8B1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AIG1 family.|||By dihydrotestosterone (DHT).|||Cell membrane|||Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids (By similarity). Shows a preference for FAHFAs with branching distal from the carboxylate head group of the lipids (By similarity).|||Membrane http://togogenome.org/gene/10090:Rps27rt ^@ http://purl.uniprot.org/uniprot/Q6ZWU9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS27 family.|||Binds 1 zinc ion per subunit.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Required for proper rRNA processing and maturation of 18S rRNAs (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Sulf1 ^@ http://purl.uniprot.org/uniprot/Q8K007 ^@ Cofactor|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Cell surface|||Endoplasmic reticulum|||Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity (By similarity). It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin (By similarity). Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation (By similarity).|||Golgi stack|||Intron retention.|||Intron retention. The sequence is a pre-RNA and intronic sequences remain.|||Processing by furin produces a secreted form.|||Secreted|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Rfng ^@ http://purl.uniprot.org/uniprot/O09009 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Detected in all the examined tissues (12.5 dpc). High expression found in adult brain.|||Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in enhancement of NOTCH1 activation by DLL1 and JAG1 (PubMed:28089369). May be involved in limb formation and in neurogenesis (By similarity).|||Golgi apparatus membrane http://togogenome.org/gene/10090:Tbc1d12 ^@ http://purl.uniprot.org/uniprot/Q6A039 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endosome|||Interacts with RAB11A; this interaction recruits TBC1D12 to RAB11A-positive recycling endosomes.|||RAB11A-binding protein that plays a role in neurite outgrowth. http://togogenome.org/gene/10090:Prok1 ^@ http://purl.uniprot.org/uniprot/Q14A28 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AVIT (prokineticin) family.|||Highly expressed in liver and ovary and weakly expressed in testis and placenta. Expressed in mucosa and mesenchyme of embryonic gut during enteric nervous system development (at protein level). Predominantly expressed in kidney and liver. Also expressed in lung, ovary, placenta and testis. In fetal liver, is restricted to and highly expressed in hepatocytes. In adult kidney, expression is restricted to the endothelial tubule cells. In placenta, expressed throughout gestation.|||In placenta, at 7.5 dpc highly expressed in ectoplacental cone, endoderm and in giant cells, and at 9.5 dpc restricted mainly to the labyrinth layer (at protein level). In placenta, most highly expressed during early gestation (between 9.5 and 10.5 dpc).|||Potently contracts gastrointestinal (GI) smooth muscle. Induces proliferation, migration and fenestration (the formation of membrane discontinuities) in capillary endothelial cells. Induces proliferation and differentiation, but not migration, of enteric neural crest cells. Directly influences neuroblastoma progression by promoting the proliferation and migration of neuroblastoma cells. Positively regulates PTGS2 expression and prostaglandin synthesis. May play a role in placentation. May play a role in normal and pathological testis angiogenesis.|||Secreted http://togogenome.org/gene/10090:Mrpl17 ^@ http://purl.uniprot.org/uniprot/Q9D8P4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL17 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Cd6 ^@ http://purl.uniprot.org/uniprot/Q61003 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ After T-cell activation, becomes hyperphosphorylated on Ser and Thr residues (By similarity). Phosphorylated on tyrosine residues in response to stimulation of the TCR complex (PubMed:24584089).|||Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166. Contributes to signaling cascades triggered by activation of the TCR/CD3 complex (PubMed:24584089). Functions as costimulatory molecule; promotes T-cell activation and proliferation. Contributes to the formation and maturation of the immunological synapse. Functions as calcium-dependent pattern receptor that binds and aggregates both Gram-positive and Gram-negative bacteria. Binds both lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteichoic acid from Gram-positive bacteria. LPS binding leads to the activation of signaling cascades and down-stream MAP kinases. Mediates activation of the inflammatory response and the secretion of pro-inflammatory cytokines in response to LPS.|||Cell membrane|||Expressed predominantly in thymus, lymph node and spleen.|||Glycosylated.|||Interacts (via extracellular domain) with ALCAM/CD166 (via extracellular domain) (PubMed:16914752). Interacts with the TCR/CD3 complex subunit CD3E. Interacts (via tyrosine phosphorylated C-terminus) with LCP2 (via SH2 domain) (PubMed:24584089). Interacts (via glycosylated extracellular domain) with LGALS1 and LGALS3. Interaction with LGALS1 or LGALS3 inhibits interaction with ALCAM (By similarity). Interacts with VAV1 (PubMed:24584089). http://togogenome.org/gene/10090:Dus1l ^@ http://purl.uniprot.org/uniprot/Q8C2P3 ^@ Function|||Similarity ^@ Belongs to the Dus family. Dus1 subfamily.|||Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. http://togogenome.org/gene/10090:Ywhah ^@ http://purl.uniprot.org/uniprot/P68510 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1 (By similarity).|||Belongs to the 14-3-3 family.|||Cytoplasm|||Homodimer (By similarity). Interacts with many nuclear hormone receptors and cofactors including AR, ESR1, ESR2, MC2R, NR3C1, NRIP1, PPARBP and THRA. Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm. Weakly interacts with CDKN1B (By similarity). Interacts with ARHGEF28 and CDK16. Interacts with KCNK18 in a phosphorylation-dependent manner. Interacts with SAMSN1. Interacts with the 'Ser-241' phosphorylated form of PDPK1 (By similarity). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (By similarity). Interacts with SLITRK1 (By similarity). Interacts with MEFV (By similarity).|||Phosphorylated on Ser-59 by protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion. http://togogenome.org/gene/10090:Stk38l ^@ http://purl.uniprot.org/uniprot/Q7TSE6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by binding of S100B which releases autoinhibitory N-lobe interactions, enabling ATP to bind and the autophosphorylation of Ser-282. Thr-442 then undergoes calcium-dependent phosphorylation by STK24/MST3. Interactions between phosphorylated Thr-442 and the N-lobe promote additional structural changes that complete the activation of the kinase. Autoinhibition is also released by the binding of MOB1/MOBKL1A and MOB2 to the N-terminal of STK38L (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm|||Highly expressed in the large and small intestine, stomach and testis. High levels also present in the brain, in particular the neurocortex, basal forebrain, hippocampus, the amygdala, cerebellum and brainstem.|||Homodimeric S100B binds two molecules of STK38L. Interacts with MOB1 and MOB2 (By similarity). Interacts with MICAL1; leading to inhibit the protein kinase activity by antagonizing activation by MST1/STK4.|||Involved in the regulation of structural processes in differentiating and mature neuronal cells.|||Membrane|||cytoskeleton http://togogenome.org/gene/10090:Pdcd2l ^@ http://purl.uniprot.org/uniprot/Q8C5N5 ^@ Function ^@ Over-expression suppresses AP1, CREB, NFAT, and NF-kB transcriptional activation, and delays cell cycle progression at S phase. http://togogenome.org/gene/10090:Or7g29 ^@ http://purl.uniprot.org/uniprot/Q8VFF4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aox3 ^@ http://purl.uniprot.org/uniprot/G3X982|||http://purl.uniprot.org/uniprot/Q9CW59 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:23263164).|||Belongs to the xanthine dehydrogenase family.|||Binds 1 FAD per subunit.|||Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Binds 2 [2Fe-2S] clusters per subunit.|||Cytoplasm|||Highly expressed in liver (at protein level). In liver, the expression is greater in males than females.|||Homodimer.|||Induced by testosterone.|||Inhibited by potassium cyanide, menadione, benzamidine, raloxifene and norharmane.|||Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and phthalazine, as well as aldehydes, such as benzaldehyde, retinal and pyridoxal. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. http://togogenome.org/gene/10090:Cpsf2 ^@ http://purl.uniprot.org/uniprot/O35218|||http://purl.uniprot.org/uniprot/Q3UGU6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Involved in the histone 3' end pre-mRNA processing (By similarity).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with CPSF3, CSTF2 and SYMPK (By similarity). Interacts with ZC3H3 (PubMed:16115198).|||Nucleus http://togogenome.org/gene/10090:Igfbp5 ^@ http://purl.uniprot.org/uniprot/Q07079|||http://purl.uniprot.org/uniprot/Q3UQV0 ^@ Caution|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Most abundant in kidney, uterus and gastrocnemius muscle.|||Secreted http://togogenome.org/gene/10090:Defb50 ^@ http://purl.uniprot.org/uniprot/Q6TU36 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has bactericidal activity.|||Highly expressed in prostate. Not expressed in uterus, epididymis, ovary, testis, spleen, submaxillary gland, thymus, thyroid, pancreas, smooth muscle, skeletal muscle, heart, kidney, lung, liver, eye and brain.|||Secreted http://togogenome.org/gene/10090:Plscr1 ^@ http://purl.uniprot.org/uniprot/Q9JJ00 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholipid scramblase family.|||Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific distribution of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatidylserine externalization on the cell surface (PubMed:32110987). Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with TRPC5 (PubMed:32110987). Also exhibits magnesium-dependent nuclease activity against double-stranded DNA and RNA but not single-stranded DNA and can enhance DNA decatenation mediated by TOP2A (By similarity). Negatively regulates FcR-mediated phagocytosis in differentiated macrophages (PubMed:26745724). May contribute to cytokine-regulated cell proliferation and differentiation (PubMed:12010804).|||Cell membrane|||Cytoplasm|||Forms homooligomers in the presence of calcium (By similarity). Interacts with ABL (By similarity). Interacts with RELT, RELL1 and RELL2 (By similarity). Interacts with OXSR1 in the presence of RELT (By similarity). Interacts with OCLN, TOP2A and TOP2B (By similarity). Interacts with TRPC1, TRPC4 and TRPC5 (PubMed:32110987). Interacts with ILDR1 (By similarity).|||Highly expressed in kidney, lung, liver and bone marrow, slightly in spleen, heart and macrophage.|||Knockout newborn mice display a reduced granulocyte production (PubMed:12010804). Hematopoietic precursor cell from knockout mice display defective colony formation and impaired differentiation to mature granulocytes as stimulated by SCF/KITL and GCSF/CSF3 (PubMed:12010804). Deletion mutant mice start to die at 3 days post-infection after influenza H1N1 challenge, and the survival rate drops to 50% at 28 days post-infection showing lower survival rate than WT mice.|||Magnesium. Can also use zinc with lower efficiency.|||Nucleus|||Palmitoylation is required for its phospholipid scramblase activity (By similarity). Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus (By similarity).|||Participates in a chromosomal translocation that produces MMTRA1A which is leukemogenic to syngenic SL mice and athymic nude mice.|||Phosphorylation at Thr-170 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis (By similarity). Phosphorylated by OXSR1 in the presence of RELT (By similarity).|||The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity.|||The transmembrane domain is essential for membrane insertion, phospholipid scramblase activity and proper calcium-binding.|||Up-regulated by SCF/KITL and GCSF/CSF3.|||perinuclear region http://togogenome.org/gene/10090:Styxl2 ^@ http://purl.uniprot.org/uniprot/Q148W8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||May be required for myofiber maturation.|||Ser-225 is present instead of the conserved Cys which is expected to be an active site residue suggesting that this protein has lost its phosphatase activity.|||sarcomere http://togogenome.org/gene/10090:Bop1 ^@ http://purl.uniprot.org/uniprot/P97452 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat BOP1/ERB1 family.|||Component of the PeBoW complex, composed of BOP1, PES1 and WDR12 (PubMed:15225545, PubMed:17353269). The complex is held together by BOP1, which interacts with PES1 via its N-terminal domain and with WDR12 via a high-affinity interaction between the seven-bladed beta-propeller domains of the 2 proteins. The NOP7 complex associates with the 66S pre-ribosome. The PeBoW complex associates with DDX27, BOP1 interacts directly with DDX27 (By similarity).|||Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.|||Expressed in brain, gut, heart, kidney, liver, lung, muscle, ovary, skin, spleen and testis.|||Expression in quiescent fibroblasts is induced by serum stimulation.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Crls1 ^@ http://purl.uniprot.org/uniprot/A0A0C3SFZ5|||http://purl.uniprot.org/uniprot/Q80ZM8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CDP-alcohol phosphatidyltransferase class-I family.|||Catalyzes the synthesis of cardiolipin (CL) (diphosphatidylglycerol) by specifically transferring a phosphatidyl group from CDP-diacylglycerol to phosphatidylglycerol (PG). CL is a key phospholipid in mitochondrial membranes and plays important roles in maintaining the functional integrity and dynamics of mitochondria under both optimal and stress conditions.|||Knockout mice have severely reduced cardiolipin (CL) (diphosphatidylglycerol) in mitochondrial membranes.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Mcm8 ^@ http://purl.uniprot.org/uniprot/Q9CWV1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MCM family.|||Chromosome|||Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity. Probably by regulating the localization of the MNR complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs. The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression. However, may play a non-essential for DNA replication: may be involved in the activation of the prereplicative complex (pre-RC) during G(1) phase by recruiting CDC6 to the origin recognition complex (ORC) (By similarity). Probably by regulating HR, plays a key role during gametogenesis (PubMed:22771120). Stabilizes MCM9 protein (By similarity).|||Component of the MCM8-MCM9 complex, which forms a hexamer composed of MCM8 and MCM9. Interacts with the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Interacts with RAD51; the interaction recruits RAD51 to DNA damage sites. Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1. Interacts with CDC6 and ORC2. Interacts with HROB; the interaction recruits the MCM8-MCM9 complex to DNA damage sites (By similarity).|||Mice are viable but are sterile due to defects in double-strand break repair during gametogenesis. Testes are apoptotic and contain spermatocytes that have persistent DNA damage and unsynapsed chromosomes due to defective homologous recombinatio. Ovaries are characterized by an early block of follicle development, and they later develop tumors.|||Nucleus http://togogenome.org/gene/10090:Prkch ^@ http://purl.uniprot.org/uniprot/P23298|||http://purl.uniprot.org/uniprot/Q3UKY1 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis.|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.|||Cytoplasm|||Interacts with FYN (PubMed:11106751). Interacts with RALA (PubMed:21346190). Interacts with DGKQ (By similarity).|||Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation.|||Predominantly expressed in lung and skin.|||The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain. http://togogenome.org/gene/10090:Gip ^@ http://purl.uniprot.org/uniprot/P48756 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glucagon family.|||Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion.|||Secreted http://togogenome.org/gene/10090:Tafa4 ^@ http://purl.uniprot.org/uniprot/Q7TPG5 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TAFA family.|||Expressed in a descrete subset of dorsal root ganglia neurons called C-low-threshold mechanoreceptors (at protein level) (PubMed:24139797). Expressed in LPS-stimulated monocytes and macrophages, especially in polarized M1 (PubMed:25109685).|||Modulates injury-induced and chemical pain hypersensitivity (PubMed:24139797). Ligand of FPR1, can chemoattract macrophages, promote phagocytosis and increase ROS release (PubMed:25109685).|||Mutant mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury.|||Secreted|||Up-regulated in LPS-stimulated monocytes and macrophages, especially in polarized M1. http://togogenome.org/gene/10090:Stau2 ^@ http://purl.uniprot.org/uniprot/Q8CJ67 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum|||Expressed in brain and neurons, where isoform 2 and isoform 3 appear to be the most abundant. Expressed at the neuromuscular junction of the extensor digitorum longus, tibialis anterior and soleus muscles. Expression at neuromuscular junctions is most pronounced in slow-twitch muscle. Also weakly expressed in heart, kidney, ovary and testis.|||Expression in extrasynaptic regions of muscle is induced by denervation. Expression in myoblasts is induced during differentiation into myotubes and by treatment with nerve derived trophic factors such as AGRN (agrin) and NRG1 (neuregulin).|||Interacts with microtubules. Isoform 2 and isoform 3 may also interact with ribosomes, and this association is independent of translation (By similarity). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Interacts with the exportin XPO5. This requires RNA and RAN bound to GTP. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (By similarity).|||Nucleus|||RNA-binding protein required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite. As protein synthesis occurs within the dendrite, the localization of specific mRNAs to dendrites may be a prerequisite for neurite outgrowth and plasticity at sites distant from the cell body (By similarity).|||The DRBM 3 domain appears to be the major RNA-binding determinant. This domain also mediates interaction with XPO5 and is required for XPO1/CRM1-independent nuclear export.|||nucleolus http://togogenome.org/gene/10090:Cyp4a31 ^@ http://purl.uniprot.org/uniprot/F8WGU9|||http://purl.uniprot.org/uniprot/Q91WU1 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Rbm14 ^@ http://purl.uniprot.org/uniprot/Q8C2Q3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with NCOA6, CITED1 and XRCC5/KU86. Interacts with SS18. Interacts with STIL and interferes with its interaction with CENPJ. Interacts with gamma-tubulin. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA.|||May function as a nuclear receptor coactivator, enhancing transcription through other coactivators such as NCOA6 and CITED1 (By similarity). Regulates centriole biogenesis by suppressing the formation of aberrant centriolar protein complexes in the cytoplasm and thus preserving mitotic spindle integrity (PubMed:25385835). Prevents the formation of the STIL-CENPJ complex (which can induce the formation of aberrant centriolar protein complexes) by interfering with the interaction of STIL with CENPJ (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Cmc2 ^@ http://purl.uniprot.org/uniprot/Q8K199 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CMC family.|||May be involved in cytochrome c oxidase biogenesis.|||Mitochondrion http://togogenome.org/gene/10090:Xk ^@ http://purl.uniprot.org/uniprot/Q059K7|||http://purl.uniprot.org/uniprot/Q9QXY7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the XK family.|||Endoplasmic reticulum membrane|||Heterodimer with Kell; disulfide-linked. Interacts with VPS13A.|||Membrane|||Recruits the lipid transfer protein VPS13A from lipid droplets to the endoplasmic reticulum (ER) membrane. http://togogenome.org/gene/10090:Cdk13 ^@ http://purl.uniprot.org/uniprot/Q69ZA1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis.|||Interacts with C1QBP (By similarity). Interacts with CCNK, CCNL1 and CCNL2.|||Nucleus speckle http://togogenome.org/gene/10090:Prkaca ^@ http://purl.uniprot.org/uniprot/P05132 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. Protein kinase A holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits which keep the enzyme in an inhibited state before activation by cyclic-AMP. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with PRKAR1A and PRKAR2B (By similarity). Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes. Interacts with APOBEC3G and AICDA (By similarity). Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly (By similarity). Found in a complex at least composed of MROH2B isoform 2, PRKACA isoform 2 and TCP11 (PubMed:27105888). Interacts with MROH2B isoform 2 (PubMed:27105888). Interacts with HSF1 (By similarity). Isoform 2 interacts with TCP11 (PubMed:27105888). Interacts with TBC1D31; in the regulation of OFD1 (By similarity). Interacts in free form with SMO (via C-terminus); the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors (PubMed:33886552).|||Accumulates in oocytes before fertilization but fades out after fertilization.|||Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis.|||Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively.|||Autophosphorylated; phosphorylation is enhanced by vitamin K(2) (By similarity). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (PubMed:8395513, PubMed:9707564). Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (PubMed:21866565).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.|||Cell membrane|||Cytoplasm|||Frequent early postnatal lethality. Survivals are runted accompanied with mature sperm exhibiting defective forward motility.|||Membrane|||Mitochondrion|||Nucleus|||Phosphorylates a large number of substrates in the cytoplasm and the nucleus (By similarity). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:10805756, PubMed:19223768). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (By similarity). RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (By similarity). Involved in chondrogenesis by mediating phosphorylation of SOX9 (PubMed:10805756). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (PubMed:33886552). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (PubMed:33886552). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (By similarity). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (PubMed:19223768). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (By similarity). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (By similarity).|||Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.|||Sperm-specific.|||When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3.|||acrosome|||flagellum http://togogenome.org/gene/10090:Msc ^@ http://purl.uniprot.org/uniprot/O88940 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer. Forms a heterodimer with TCF3.|||Expression in embryos is largely restricted to embryonic skeletal muscle lineage. First detected at 9.5 dpc in cells within the first and second branchial arches. At 10.5 dpc, expression was also observed in the myotomal compartment of rostral somites and by 11.5 dpc in myotomes along the whole anterio-posterior axis, as well as in cells within the developing forelimbs and hindlimbs. At 12.5-14.5 dpc, expression was confined to the skeletal muscle lineage (head, neck, trunk, limbs and diaphragm but not cardiac and smooth muscle). At 15 dpc, a peak expression was seen in neonatal limbs.|||Nucleus|||Transcription repressor that blocks myogenesis and activation of E-box dependent muscle genes. http://togogenome.org/gene/10090:Or2a54 ^@ http://purl.uniprot.org/uniprot/Q8VFS5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Usp46 ^@ http://purl.uniprot.org/uniprot/P62069 ^@ Function|||Similarity|||Subunit ^@ Belongs to the peptidase C19 family. USP12/USP46 subfamily.|||Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67 (PubMed:19465912). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity. Not involved in deubiquitination of monoubiquitinated FANCD2 (By similarity).|||Interacts with WDR48. Interacts with WDR20. http://togogenome.org/gene/10090:Apol11b ^@ http://purl.uniprot.org/uniprot/E9PUZ0 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Igfbp6 ^@ http://purl.uniprot.org/uniprot/P47880 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Activates the MAPK signaling pathway and induces cell migration.|||Interacts (via C-terminal domain) with PHB2.|||O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Gm20816 ^@ http://purl.uniprot.org/uniprot/Q5FWD4 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Fxyd3 ^@ http://purl.uniprot.org/uniprot/Q3TLM3|||http://purl.uniprot.org/uniprot/Q61835 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell (PubMed:15743908). Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1 (By similarity). Induces a hyperpolarization-activated chloride current when expressed in Xenopus oocytes (By similarity).|||Belongs to the FXYD family.|||Cell membrane|||Expressed at high levels in heart, skeletal muscle and liver with low levels of expression in breast, brain, lung, stomach and colon (PubMed:7836447). In the gastric gland, mainly expressed in the mucus cells forming the upper part of the gland and is absent from the parietal cells (PubMed:15743908).|||Glutathionylated.|||Marker of a cell type preferentially transformed by neu or ras oncoprotein.|||Regulatory subunit of the sodium/potassium-transporting ATPase which is composed of a catalytic alpha subunit, a non-catalytic beta subunit and an additional regulatory subunit (PubMed:15743908). Interacts with catalytic alpha subunit ATP1A1 (PubMed:15743908). Also interacts with non-catalytic beta subunit ATP1B1 (PubMed:15743908). Interacts with the ATP1A1-ATP1B1, ATP1A2-ATP1B1 and ATP1A3-ATP1B1 NKA isozymes (By similarity). http://togogenome.org/gene/10090:Adcy8 ^@ http://purl.uniprot.org/uniprot/A0A2I3BQ46|||http://purl.uniprot.org/uniprot/P97490|||http://purl.uniprot.org/uniprot/Q3UUN2 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed within the olfactory bulb, thalamus, habenula, CA1 region of the hippocampus, and hypothalamus (PubMed:10864938). Strongly expressed in pyramidal cells of CA1 and weakly in CA3 and the dentate gyrus. Strongly and homogeneously expressed in all cell layers of the anterior cingulate cortex (ACC). Widely expressed in the insular cortex. Weakly expressed in the spinal dorsal horn (PubMed:12441059). Abundantly present in the CA1/CA2 region in the hippocampus neonatal and intensifies by adulthood. Weakly expressed in the cerebellum at postnatal day 7 and decreased further by postnatal day 14 (PubMed:17335981).|||Adcy8 knockout mice are fertile and seem normal. However mice reveal a tendency for both male and female to be somewhat smaller from day of life 45 and 30 respectively while food intake is normal. From there, females remain 10-15% smaller. In contrast, male transiently grew more slowly between day of life 45 and 92, after which point differences are not significant. Mice are less nervous.|||Apical cell membrane|||At rest, the N- and C-terminal domains interact, as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain. Upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain. Fully calcium-saturated calmodulin then leaves the N-terminal domain, binding solely to the C-terminal domain, and the whole autoinhibitory complex dissociates, resulting in activation of adenylate cyclase. As local calcium concentrations decrease, the calmodulin becomes calcium free and binds once more to the N-terminal domain, whereupon the whole system returns to rest with the re-association of the autoinhibitory complex (PubMed:14585998). In non-excitable cells, activated by capacitative calcium entry (CCE) through store-operated channels, namely through interaction with ORAI1 and STIM1; membrane raft and caveolae localization and membrane integrity are indispensable. CCE-mediated adenylate cyclase activity is decreased by AKAP5 and AKAP7. CCE-mediated adenylate cyclase activity is up-regulated by AKAP9 and the mitochondrially targeted AKAP1. In excitable cells, activated during membrane depolarization through L-type voltage-gated calcium channels (VGCC), leading to calcium entry; the L-type alpha subunit is sufficient. Activated via stimulation of the GLP1R. Synergistically activated by calcium/calmodulin and GNAS. Stimulated by forskolin. Inhibited by PKA directly bound to AKAP5 at membrane raft. Inhibition by acute activation of OPRM1 and activation by chronic activation of OPRM1 is mediated by pertussis toxin-sensitive G(i) and G(o) G alpha proteins and G beta-gamma dimer. Activity is inhibited by G beta-gamma dimer (By similarity).|||Basolateral cell membrane|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of cAMP in response to calcium entry leadings to cAMP signaling activation that affect processes suche as synaptic plasticity and insulin secretion (PubMed:10864938, PubMed:25403481, PubMed:10482244, PubMed:14585998, PubMed:18448650). Plays a role in many brain functions, such as learning, memory, drug addiction, and anxiety modulation through regulation of synaptic plasticity by modulating long-term memory and long-term potentiation (LTP) through CREB transcription factor activity modulation (PubMed:10482244, PubMed:14585998, PubMed:18448650, PubMed:10864938, PubMed:12441059, PubMed:20638449, PubMed:27234425, PubMed:18222416). Plays a central role in insulin secretion by controlling glucose homeostasis through glucagon-like peptide 1 and glucose signaling pathway and maintains insulin secretion through calcium-dependent PKA activation leading to vesicle pool replenishment (PubMed:25403481). Also, allows PTGER3 to induce potentiation of PTGER4-mediated PLA2 secretion by switching from a negative to a positive regulation, during the IL1B induced-dedifferentiation of smooth muscle cells (By similarity).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.|||Cell membrane|||Homodimer; via transmembrane domain (PubMed:19158400). Monomer (PubMed:19158400). Heterodimer. Oligemer; via transmembrane domain. Interacts with PRKAR2A and AKAP5; inhibits adenylate cyclase activity through PKA phosphorylation. Interacts with PPP2CA and PPP2R1A; does not mediate the inhibitory effects of PKA on adenylate cyclase activity; interaction is dependent of catalytically active PPP2CA; antagonizes interaction with calmodulin. Interacts with AKAP5 (palmitoylated form); promotes the phosphorylation of ADCY8 after store-operated calcium entry (SOCE) stimulation at membrane raft. Interacts with ORAI1; interaction is calcium store depletion independent; interaction occurs in membrane raft; interaction increases markedly after store depletion; positively regulates SOCE-induced adenylate cyclase activity; contributes to the targeting of ADCY8 to discrete regions of the plasma membrane that are shielded from other calcium events. Interacts with STIM1. Interacts with actin; interaction is calcium independent; interaction is affected by calcium-calmodulin; interaction controls the distribution and regulation of ADCY8. Interacts with calmodulin; at rest, interacts via N-terminal domain; upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain forming an autoinhibitory complex; fully calcium-saturated calmodulin leaves the N-terminal domain, binding solely to the C-terminal domain leading to dissociation of autoinhibitory complex and resulting in activation of adenylate cyclase; antagonizes interaction with PPP2CA; interaction is calcium dependent. Interacts with PPP2R5D (By similarity).|||Membrane|||Membrane raft|||N-glycosylated; N-glycosylation is responsible for raft-targeting; is not necessary for CCE-stimulated adenylate cyclase activity.|||Phosphorylated by PKA; mediates inhibition of adenylate cyclase activity at membrane raft; does not influence either CALM1 or PPP2CA interaction with ADCY8.|||Postsynaptic density|||Presynaptic cell membrane|||Synapse|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. The two transmembrane clusters are necessary and suficient for the plasma membrane targeting and oligomers assembly. The N-terminal and C-terminal domains interact at rest as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain; the binding is specifically inhibited by fully calcium-saturated calmodulin, resulting in activation of AC8.|||axon|||caveola|||clathrin-coated vesicle membrane|||coated pit|||dendrite http://togogenome.org/gene/10090:Or10p1 ^@ http://purl.uniprot.org/uniprot/Q8VGJ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Eme1 ^@ http://purl.uniprot.org/uniprot/Q8BJW7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EME1/MMS4 family.|||Interacts with MUS81 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks.|||May self-associate (By similarity). Interacts with MUS81.|||Weakly expressed in brain, heart, kidney, liver, lung, muscle, skin, small intestine, spleen, stomach, testis and thymus (PubMed:14609959, PubMed:27010503). Expressed in bone marrow (PubMed:27010503). Also expressed in embryonic stem cells (ES cells) (PubMed:14609959).|||nucleolus http://togogenome.org/gene/10090:Kap ^@ http://purl.uniprot.org/uniprot/P61110 ^@ Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By androgens.|||Kidney, submaxillary gland, urine.|||Secreted http://togogenome.org/gene/10090:Mpv17 ^@ http://purl.uniprot.org/uniprot/E9Q1I6|||http://purl.uniprot.org/uniprot/G3UVW1|||http://purl.uniprot.org/uniprot/P19258 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peroxisomal membrane protein PXMP2/4 family.|||High levels in heart, kidney, and brain, intermediate levels in testis, and low levels in liver and spleen.|||Membrane|||Mice lack expression of this protein resulting in the development of adult onset nephrotic syndrome and chronic renal failure. They also develop severe morphological degeneration of the inner ear. In the inner ear, mice lacking Mpv17 display degenerative changes of the cochlear structures already at the age of 2 months. The degenerative changes are patchy arranged throughout the entire length of the cochlea and involved the organ of Corti as well as the stria vascularis epithelia with alterations of the basement membrane of the capillaries.|||Mitochondrion inner membrane|||Non-selective channel that modulates the membrane potential under normal conditions and oxidative stress, and is involved in mitochondrial homeostasis (By similarity). Involved in mitochondrial deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial DNA (mtDNA) maintenance (PubMed:26760297). May be involved in the regulation of reactive oxygen species metabolism and the control of oxidative phosphorylation (Probable).|||Was initially thought to be a peroxisomal protein (PubMed:7957077). However, it was later shown in human that it is a mitochondrial protein (PubMed:16582907, PubMed:16582910). http://togogenome.org/gene/10090:Fam118a ^@ http://purl.uniprot.org/uniprot/Q91YN1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM118 family.|||Membrane http://togogenome.org/gene/10090:Zc3h12c ^@ http://purl.uniprot.org/uniprot/E9Q1I3|||http://purl.uniprot.org/uniprot/Q5DTV4 ^@ Function|||Induction|||Similarity ^@ Belongs to the ZC3H12 family.|||By bacterial lipopolysaccharides (LPS) in macrophage cell line RAW 264.7.|||May function as RNase and regulate the levels of target RNA species. http://togogenome.org/gene/10090:Gpd2 ^@ http://purl.uniprot.org/uniprot/Q64521 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAD-dependent glycerol-3-phosphate dehydrogenase family.|||Calcium-binding enhance the activity of the enzyme.|||Calcium-responsive mitochondrial glycerol-3-phosphate dehydrogenase which seems to be a key component of the pancreatic beta-cell glucose-sensing device.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pgam1 ^@ http://purl.uniprot.org/uniprot/Q3U7Z6|||http://purl.uniprot.org/uniprot/Q9DBJ1 ^@ Function|||PTM|||Similarity|||Subunit ^@ Acetylated at Lys-253, Lys-253 and Lys-254 under high glucose condition. Acetylation increases catalytic activity. Under glucose restriction SIRT1 levels dramatically increase and it deacetylates the enzyme (By similarity).|||Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.|||Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate. Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate.|||Homodimer. http://togogenome.org/gene/10090:Siglecf ^@ http://purl.uniprot.org/uniprot/Q920G3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Membrane|||Predominantly expressed by immature monocytic/myeloid lineage cells in bone marrow. Also found at lower levels in mature neutrophils and monocytes.|||Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. http://togogenome.org/gene/10090:Ush1g ^@ http://purl.uniprot.org/uniprot/Q80T11 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cajal body|||Cell membrane|||Defects in Ush1g are the cause of the Jackson shaker phenotypes (js). Jackson shaker mice carry recessive mutations predicted to inactivate Ush1g by frameshift resulting in a truncated protein lacking the C-terminal SAM domain. The js phenotype is characterized by deafness, abnormal behavior (circling and/or head-tossing) and degeneration of inner ear neuroepithelia. Defects in the formation of protein complex including Ush1g may disrupt stereocilia bundle in js mice.|||Detected in stereocilia from cochlear hair cells (at protein level). Detected in retinal photoreceptor cell cilia (at protein level) (PubMed:31637240). Highly expressed in the cochlea, testis, cerebellum and eye, and low levels in brain, thymus and spleen. Significant signals detected in the neurosensory epithelium of inner ear cochlea and saccule, especially in inner and outer hair cells.|||Low-level expression detected in 17.5 dpc embryos but not in embryos earlier than 15.5 dpc.|||Mice are deaf, due to defects in hair cell bundles in the cochlea (PubMed:21436032). They develop circling behavior, probably due to balance problems (PubMed:21436032). Reduced expression of Ift20, Ift52 and Ift57 in the ciliary region of photoreceptor cells (PubMed:31637240).|||Nucleus speckle|||Part of a complex composed of USH1C, USH1G and MYO7A (By similarity). Interacts with USH1C (via the first PDZ domain) (PubMed:12588794). Interacts with PDZD7 (By similarity). Interacts with CDH23 and PCDH15; these interactions may recruit USH1G to the plasma membrane (PubMed:21436032). Interacts with intraflagellar transport proteins IFT20, IFT52 and IFT57 (By similarity). Interacts with splicing factors SF3B1, PRPF6, PRPF31 and SON (By similarity). Interacts with the U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complex in the presence of pre-mRNAs (By similarity). Interacts (via SAM domain) with MAGI2 (via PDZ 6 domain); the interaction is triggered by phosphorylation of USH1G by CK2 and negatively regulates MAGI2-mediated endocytosis (PubMed:24608321).|||Photoreceptor inner segment|||Plays a role in pre-mRNA splicing by regulating the release and transfer of U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complexes from their assembly site in Cajal bodies to nuclear speckles, thereby contributing to the assembly of the pre-catalytic spliceosome on target pre-mRNAs (By similarity). May also participate in recycling of snRNPs back to Cajal bodies during splicing (By similarity). Plays a role in regulating MAGI2-mediated endocytosis (By similarity). Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles. Required for normal hearing.|||centrosome|||cilium|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Spata46 ^@ http://purl.uniprot.org/uniprot/Q4FZF2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Deficient mice develop and grow normally. Knockout males, but not females, exhibit subfertile capacity. Deficient mice are characterized by abnormal sperm head shape and a failure of sperm-egg fusion (PubMed:27488028).|||Increases in the third week postnatal and gradually increased until the adult stage (PubMed:27488028).|||Nucleus membrane|||Plays a role in spermiogenesis and fertilization.|||Testis-specific (PubMed:27488028). http://togogenome.org/gene/10090:Ppm1e ^@ http://purl.uniprot.org/uniprot/B2KGP3|||http://purl.uniprot.org/uniprot/Q80TL0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Cytoplasm|||Heterotrimer. Interacts with PAX1 and ARHGEF6 (or ARHGEF7) (By similarity).|||Nucleus|||Protein phosphatase that inactivates multifunctional CaM kinases such as CAMK4 and CAMK2. Dephosphorylates and inactivates PAK. May play a role in the inhibition of actin fiber stress breakdown and in morphological changes driven by TNK2/CDC42 (By similarity). Dephosphorylates PRKAA2. http://togogenome.org/gene/10090:Mef2d ^@ http://purl.uniprot.org/uniprot/E9QKT0|||http://purl.uniprot.org/uniprot/Q63943|||http://purl.uniprot.org/uniprot/Q921S6 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated on Lys-432 by CREBBP. Acetylated by EP300. Deacetylated by SIRT1 and HDAC3 (By similarity).|||Belongs to the MEF2 family.|||Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation, HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with HDAC4 (in undifferentiating cells); the interaction translocates MEF2D to nuclear dots. Forms a heterodimer with MEF2A (By similarity). Interacts with MAPK7; the interaction phosphorylates but does not activate MEF2D (By similarity). Interacts with MYOG. Interacts with CCAR2 and HDAC3 (By similarity).|||In the developing cerebellum, increasing levels after birth. The majority of this increase occurs around postnataL day 9 reaching a peak at postnatal day 15-18 which is maintained in adults.|||Nucleus|||Phosphorylated on Ser-437 is which is required for Lys-432 sumoylation and inhibits transcriptional activity. Phosphorylation on this residue by CDK5 is dependent on p35 and calpains. Phosphorylated by PKA at Ser-121 and Ser-190 represses transcriptional activity in embryonic and postnatal skeletal muscle, and stabilizes protein levels. No in vitro phosphorylation by PKA on Thr-20. Phosphorylated and activated by CaMK4 (By similarity).|||Proteolytically cleaved in cerebellar granule neurons by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation.|||Sumoylated on Lys-432 with SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3 (By similarity).|||Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis.|||Widely expressed though mainly restricted to skeletal and cardiac muscle, brain, neurons and lymphocytes. Differentially expressed depending on if isoforms contain the beta domain or not, with the total expression of the beta domain-lacking isoforms vastly exceding that of the beta domain-containing isoforms. Isoforms containing the beta domain are expressed primarily in skeletal and cardiac muscle and in brain. Also present in lung and testis. Splicing to include the beta domain is induced in differentiating myocytes. Isoforms lacking the beta domain are expressed less abundantly in skeletal muscle, brain and lymphocytes, and are uniquely found in ovary, liver, spleen and kidney. In embryos, the beta domain-containing and beta domain-lacking isoforms are equally expressed. Also expressed cerebellar granule neurons and other regions of the CNS. Highest levels in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum. http://togogenome.org/gene/10090:Suv39h1 ^@ http://purl.uniprot.org/uniprot/A2AC19|||http://purl.uniprot.org/uniprot/O54864 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-266, leading to inhibition of enzyme activity. SIRT1-mediated deacetylation relieves this inhibition (By similarity).|||Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin.|||Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.|||Expression present throughout embryogenesis. Higher expression between 9.5 dpc and 13 dpc.|||Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.|||In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.|||Incomplete sequence.|||Interacts with CCAR2 and GFI1B. Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8 (By similarity). Interacts with H3 and H4 histones. Interacts with DNMT3B, CBX1, CBX4, MBD1, RUNX1, RUNX3, MYOD1, SMAD5 and RB1. Interacts with SBF1 through the SET domain. Interacts with HDAC1 and HDAC2 through the N-terminus and associates with the core histone deacetylase complex composed of HDAC1, HDAC2, RBBP4 and RBBP7. Interacts (via SET domain) with MECOM; enhances MECOM transcriptional repression activity. Interacts with LMNA; the interaction increases stability of SUV39H1. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex.|||Mice lacking Suv39h1 and Suv39h2 display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. They also show a higher level of histone H3 with phosphorylated 'Ser-10' and a reduced number of cells in G1 phase and an increased portion of cells with aberrant nuclear morphologies.|||Negatively regulated by CCAR2.|||Nucleus|||Nucleus lamina|||Phosphorylated on serine residues, and to a lesser degree, on threonine residues.|||Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.|||Widely expressed.|||centromere|||nucleoplasm http://togogenome.org/gene/10090:Or4c118 ^@ http://purl.uniprot.org/uniprot/A0A1L1SU13 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nlrp2 ^@ http://purl.uniprot.org/uniprot/Q4PLS0 ^@ Similarity ^@ Belongs to the NLRP family. http://togogenome.org/gene/10090:Hspa13 ^@ http://purl.uniprot.org/uniprot/D3Z0Y0|||http://purl.uniprot.org/uniprot/Q8BM72 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 70 family.|||Binds UBQLN2.|||Endoplasmic reticulum|||Has peptide-independent ATPase activity.|||Microsome http://togogenome.org/gene/10090:Hoxb6 ^@ http://purl.uniprot.org/uniprot/P09023 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Fam222b ^@ http://purl.uniprot.org/uniprot/Q6P539 ^@ Similarity ^@ Belongs to the FAM222 family. http://togogenome.org/gene/10090:Axl ^@ http://purl.uniprot.org/uniprot/Q00993|||http://purl.uniprot.org/uniprot/Q6PE80|||http://purl.uniprot.org/uniprot/Q8CCF8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by GAS6-binding and subsequent autophosphorylation.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.|||Cell membrane|||Heterodimer and heterotetramer with ligand GAS6 (By similarity). Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2 (By similarity).|||In distinct substructures of a broad spectrum of developing tissues (in the late embryogenesis). In cells forming organ capsules as well as in connective tissue structures (in adult).|||Membrane|||Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion (By similarity).|||Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.|||Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. http://togogenome.org/gene/10090:Klra9 ^@ http://purl.uniprot.org/uniprot/Q2TJJ8|||http://purl.uniprot.org/uniprot/Q64329 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked.|||Membrane|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Cdh26 ^@ http://purl.uniprot.org/uniprot/P59862 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Ligand for integrins alpha-E/beta-7, ITGAE:ITGAB7, alpha-4/beta-7, ITGA4:ITGAB7 and alpha-4/beta-1, ITGA4:ITGAB1 through which modulates CD4(+) T cells activation.|||Cell membrane|||Homodimer. Component of a cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1.|||N-glycosylated.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Keap1 ^@ http://purl.uniprot.org/uniprot/Q9Z2X8 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ According to a report, not degraded in response to autophagy (PubMed:20495340). However, publications have shown that KEAP1 is degraded via a proteasomal-independent process during selective autophagy (PubMed:22872865, PubMed:24011591).|||Auto-ubiquitinated by the BCR(KEAP1) complex. Quinone-induced oxidative stress, but not sulforaphane, increases its ubiquitination. Ubiquitination and subsequent degradation is most pronounced following prolonged exposure of cells to oxidative stress, particularly in glutathione-deficient cells that are highly susceptible to oxidative stress.|||Belongs to the KEAP1 family.|||Component of the BCR(KEAP1) E3 ubiquitin ligase complex, at least composed of 2 molecules of CUL3, 2 molecules of KEAP1, and RBX1 (PubMed:15282312, PubMed:16790436, PubMed:27697860). Interacts with NFE2L2/NRF2; the interaction is direct (PubMed:15282312, PubMed:15367669, PubMed:15581590, PubMed:16790436, PubMed:16581765, PubMed:27697860, PubMed:16507366). Forms a ternary complex with NFE2L2/NRF2 and PGAM5 (By similarity). Interacts with (phosphorylated) SQSTM1/p62; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering it in inclusion bodies, promoting its degradation (PubMed:20495340, PubMed:20421418, PubMed:20173742, PubMed:24011591). Interacts with NFE2L1 (By similarity). Interacts with BPTF and PTMA (By similarity). Interacts with MAP1LC3B (By similarity). Interacts indirectly with ENC1 (By similarity). Interacts with SESN1 and SESN2 (By similarity). Interacts with HSP90AA1 and HSP90AB1 (By similarity).|||Cytoplasm|||Degraded via a proteasomal-independent process during selective autophagy: interaction with phosphorylated SQSTM1/p62 sequesters KEAP1 in inclusion bodies, leading to its degradation.|||Early postnatal lethality caused by abnormal cornification (PubMed:14517554). Mice survive until weaning and probably die from malnutrition resulting from hyperkeratosis in the esophagus and forestomach that cause gastric obstruction (PubMed:14517554). Defects are caused by constitutive activation Nfe2l2/Nrf2, leading to constitutive expression of phase 2 detoxifying enzymes (PubMed:14517554). Mice lacking both Nfe2l2/Nrf2 and Keap1 reverse the hyperkeratosis phenotype and are healthy and viable in normal conditions (PubMed:14517554).|||KEAP1 contains reactive cysteine residues that act as sensors for endogenously produced and exogenously encountered small molecules, which react with sulfhydryl groups and modify the cysteine sensors, leading to impair ability of the BCR(KEAP1) complex to ubiquitinate target proteins.|||Non-enzymatic covalent modifications of reactive cysteines by electrophile metabolites inactivate the BCR(KEAP1) complex (PubMed:12193649, PubMed:20498371, PubMed:22014577). Accumulation of fumarate promotes the formation of cysteine S-succination (S-(2-succinyl)cysteine), leading to inactivate the BCR(KEAP1) complex and promote NFE2L2/NRF2 nuclear accumulation and activation (PubMed:22014577). Nitric oxide-dependent 8-Nitro-cGMP formation promotes cysteine guanylation (S-cGMP-cysteine), leading to NFE2L2/NRF2 nuclear accumulation and activation (PubMed:17906641, PubMed:20498371). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates cysteines, activating NFE2L2/NRF2 (PubMed:29590092). Methylglyoxal, a reactive metabolite that accumulates when the glycolytic enzyme PGK1 is inhibited, promotes formation of a methylimidazole cross-link between proximal Cys-151 and Arg-135 on another KEAP1 molecule, resulting in an inactive dimer that inactivates the BCR(KEAP1) complex (By similarity).|||Nucleus|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:9887101, PubMed:12682069, PubMed:15282312, PubMed:15367669, PubMed:15581590). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:9887101, PubMed:12193649, PubMed:14764894). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:12193649, PubMed:20498371, PubMed:22014577, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20421418, PubMed:20173742, PubMed:24011591). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (By similarity).|||The Kelch repeats mediate interaction with NFE2L2/NRF2, BPTF and PGAM5.|||The mechanism of inactivation of the BCR(KEAP1) complex by covalent modifications of reactive cysteines is unclear. Covalent modifications were initially thought to disrupt interaction between KEAP1 and NFE2L2/NRF2 (PubMed:12193649). Recent publications suggest that cysteine modifications disrupt the interaction between KEAP1 and CUL3 without affecting the interaction between KEAP1 and NFE2L2/NRF2 (By similarity).|||Ubiquitin ligase activity of the BCR(KEAP1) complex is inhibited by oxidative stress and electrophile metabolites such as sulforaphane (PubMed:12193649, PubMed:14764894, PubMed:22014577). Electrophile metabolites react with reactive cysteine residues in KEAP1 and trigger non-enzymatic covalent modifications of these cysteine residues, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex (PubMed:20498371, PubMed:22014577). Selective autophagy also inactivates the BCR(KEAP1) complex via interaction between KEAP1 and SQSTM1/p62, which sequesters the complex in inclusion bodies and promotes its degradation (PubMed:20421418, PubMed:20173742, PubMed:24011591). http://togogenome.org/gene/10090:Tor1aip1 ^@ http://purl.uniprot.org/uniprot/E9PWW2|||http://purl.uniprot.org/uniprot/Q921T2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16 dpc, widely expressed with high expression levels in hippocampus and low levels in heart. In the spinal cord, expressed as early as 12 dpc until p21, the expression levels decrease in the adulthood (at protein level).|||Belongs to the TOR1AIP family.|||Expressed in the spinal cord and liver (at protein level).|||Interacts with ATP1B4. Interacts with TOR1A (ATP-bound). Interacts with TOR1B, TOR2A and TOR3A. Interacts with VIM.|||Membrane|||Mutant mice exhibit perinatal mortality, typically dying on the last prenatal or first postnatal day. All tissues tested exhibit nuclear membrane abnormalities with membranous vesicle-appearing structures observed in the perinuclear space of neurons.|||Nucleus inner membrane|||Required for nuclear membrane integrity. Induces TOR1A and TOR1B ATPase activity and is required for their location on the nuclear membrane. Binds to A- and B-type lamins. Possible role in membrane attachment and assembly of the nuclear lamina. http://togogenome.org/gene/10090:Bnip3l ^@ http://purl.uniprot.org/uniprot/Q9Z2F7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NIP3 family.|||Endoplasmic reticulum|||Induces apoptosis. Interacts with viral and cellular anti-apoptosis proteins. Can overcome the suppressors BCL-2 and BCL-XL, although high levels of BCL-XL expression will inhibit apoptosis. Inhibits apoptosis induced by BNIP3. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix (By similarity). May function as a tumor suppressor (By similarity).|||Membrane|||Mitochondrion outer membrane|||Nucleus envelope|||Self-associates. Interacts with BNIP3 and STEAP3. Interacts (via BH3 domain) with SPATA18 (via coiled-coil domains) (By similarity).|||Undergoes progressive proteolysis to an 11 kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin. http://togogenome.org/gene/10090:Or7a41 ^@ http://purl.uniprot.org/uniprot/Q8VGU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Id4 ^@ http://purl.uniprot.org/uniprot/P41139|||http://purl.uniprot.org/uniprot/Q544D2 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain with peak levels between CT16 and CT20.|||Heterodimer with other HLH proteins.|||Mice do not exhibit a noticeable circadian phenotype.|||Nucleus|||Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. http://togogenome.org/gene/10090:Frs2 ^@ http://purl.uniprot.org/uniprot/Q8C180 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1.|||Membrane|||Part of a complex containing FRS2, GRB2, GAB1, PIK3R1 and SOS1. Part of a complex containing GRB2 and CBL. Binds ALK, CKS2, FGFR1, RET, MAPK1/ERK2, MAPK3/ERK1 and SRC. The tyrosine-phosphorylated protein binds the SH2 domains of GRB2 and PTPN11. Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated upon ligand-binding) (By similarity). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN.|||Phosphorylated on tyrosine residues upon stimulation by FGF2 or NGFB. Phosphorylated by ULK2 (in vitro). Phosphorylated on tyrosine residues by activated ALK and FGFR1. Phosphorylated on tyrosine residues upon activation of FGFR2 and FGFR3. Phosphorylated on threonine residues by MAP kinases; this inhibits tyrosine phosphorylation, and thereby down-regulates FRS2-mediated activation of MAP kinases.|||Ubiquitinated when tyrosine phosphorylated and in a complex with GRB2. The unphosphorylated form is not subject to ubiquitination.|||Ubiquitous. Expression is highest in brain, kidney, lung and testis. http://togogenome.org/gene/10090:Pdlim5 ^@ http://purl.uniprot.org/uniprot/Q8CI51 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with various PKC isoforms through the LIM domains. Interacts with actin and alpha-actinin through the PDZ domain. Interacts (via LIM domains) with SIPA1L1/SPAR; this interaction may occur preferentially with isoform 1.|||May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation.|||Postsynapse|||Postsynaptic density|||Presynapse|||cytosol http://togogenome.org/gene/10090:Gm3376 ^@ http://purl.uniprot.org/uniprot/Q60990 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with splicing factor proteins SFRS3/SRP20, TRA2B/SFRS10, KHDRBS1/SAM68 and KHDRBS3.|||Nucleus|||Only expressed in spermatogonia and early spermatocytes, suggesting that expression is inactivated in the XY body during meiosis.|||Overexpression of Rbmy proteins in mice carrying the Y(d1) deletion that removes most of the multi-copy Rbmy gene cluster does not have any effect and fails to reduce the frequency of abnormal sperm. These results raize the question of the role of Rbmy proteins in sperm development.|||RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis.|||Testis-specific.|||The RBMY1 proteins are encoded by repeated regions of the Y chromosome. The exact number of functional copies is unclear and may vary between individuals, and some of them may represent pseudogenes. http://togogenome.org/gene/10090:Myo1e ^@ http://purl.uniprot.org/uniprot/E9Q634|||http://purl.uniprot.org/uniprot/Q8C123 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cell junction|||Cytoplasm|||Cytoplasmic vesicle|||Detected in kidney glomeruli (at protein level). Detected in utricle.|||Interacts with CALM and F-actin. Interacts (via SH3 domain) with SYNJ1, DNM1 and DNM2. Interacts with ARL14EP. Interacts with CARMIL1.|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. Binds to membranes containing anionic phospholipids via its tail domain (By similarity). Involved in clathrin-mediated endocytosis and intracellular movement of clathrin-coated ve (By similarity)sicles. Required for normal morphology of the glomerular basement membrane, normal development of foot processes by kidney podocytes and normal kidney function. In dendritic cells, may control the movement of class II-containing cytoplasmic vesicles along the actin cytoskeleton by connecting them with the actin network via ARL14EP and ARL14 (By similarity).|||No visible phenotype at birth. Mice exhibit massive proteinuria, combined with the presence of leukocytes and hemoglobin in the urine. They develop enlarged kidneys, present damage to the glomeruli, renal inflammation and fibrosis. In the glomeruli, the thickness of the basement membrane is increased, and podocytes fail to develop normal foot processes.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).|||clathrin-coated vesicle|||cytoskeleton http://togogenome.org/gene/10090:C1qa ^@ http://purl.uniprot.org/uniprot/P98086 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ C1 is a calcium-dependent trimolecular complex of C1q, R and S in the molar ration of 1:2:2. C1q subcomponent is composed of nine subunits, six of which are disulfide-linked dimers of the A and B chains, and three of which are disulfide-linked dimers of the C chain. Interacts (via C-terminus) with CD33; this interaction activates CD33 inhibitory motifs.|||C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.|||O-linked glycans are Glc-Gal disaccharides typically found as secondary modifications of hydroxylated lysines in collagen-like domains.|||Proline residues in the collagen-like domain motif, GXPG, are typically 4-hydroxylated.|||Secreted http://togogenome.org/gene/10090:Nudt9 ^@ http://purl.uniprot.org/uniprot/Q8BVU5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Nudix hydrolase family. NudF subfamily.|||Hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate.|||Mitochondrion|||Monomer. Interacts with GLOD4. http://togogenome.org/gene/10090:Afap1l2 ^@ http://purl.uniprot.org/uniprot/Q5DTU0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with SRC. Interacts with LCK when tyrosine phosphorylated (By similarity).|||May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation (By similarity).|||Tyrosine phosphorylated (by SRC). http://togogenome.org/gene/10090:Klk1b9 ^@ http://purl.uniprot.org/uniprot/P15949 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Sun2 ^@ http://purl.uniprot.org/uniprot/Q8BJS4 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for Rab5-GDP and participate in the activation of Rab5.|||Core component of the LINC complex which is composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents is giving rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. Interacts with SYNE2; the SUN2:SYNE2/KASH2 LINC complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE2/KASH2 peptides bind at the interface of adjacent SUN domains. Component of a probable SUN2:KASH5 LINC complex. Interacts with SYNE1 and SYNE3; probably forming respective LINC complexes. Interacts with A-type lamin. Interaction with lamins B1 and C is hardly detectable. Interacts with EMD. Interacts with RAB5A. Interacts with TMEM43 and TMEM201. Interacts with IRAG2 (PubMed:29878215).|||Endosome membrane|||Highly expressed in heart, placenta and muscle.|||Nucleus envelope|||Nucleus inner membrane|||The SUN domain may play a role in nuclear anchoring and/or migration.|||The disulfide bond with SYNE2 is required for stability of the SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required for the interaction. The disulfide bond is proposed to be conserved in LINC complexes involved in force transmission.|||The proximal coiled coil domain mediates trimerization required for binding to nesprins. The distal coiled coil domain is proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation (PubMed:26688217). The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton (By similarity). http://togogenome.org/gene/10090:Hoxd8 ^@ http://purl.uniprot.org/uniprot/A2ASN1|||http://purl.uniprot.org/uniprot/F6W963|||http://purl.uniprot.org/uniprot/P23463|||http://purl.uniprot.org/uniprot/Q9CUH8|||http://purl.uniprot.org/uniprot/Q9CUQ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Sel1l2 ^@ http://purl.uniprot.org/uniprot/Q3V172 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sel-1 family.|||Membrane http://togogenome.org/gene/10090:Or2a51 ^@ http://purl.uniprot.org/uniprot/Q8VFS3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vamp4 ^@ http://purl.uniprot.org/uniprot/O70480|||http://purl.uniprot.org/uniprot/Q8BSN6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type X (BoNT/X) which hydrolyzes the 87-Arg-|-Ser-88 bond and probably inhibits neurotransmitter release (PubMed:28770820). It remains unknown whether BoNT/X is ever produced, or what organisms it targets.|||Belongs to the synaptobrevin family.|||Identified in a complex containing STX6, STX12, VAMP4 and VTI1A (PubMed:17159904). Interacts with BAIAP3; this interaction is increased in the presence of calcium (By similarity).|||Involved in the pathway that functions to remove an inhibitor (probably synaptotagmin-4) of calcium-triggered exocytosis during the maturation of secretory granules. May be a marker for this sorting pathway that is critical for remodeling the secretory response of granule (By similarity).|||Membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Asxl1 ^@ http://purl.uniprot.org/uniprot/P59598|||http://purl.uniprot.org/uniprot/Q24JP2 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Asx family.|||Component of the PR-DUB complex, at least composed of BAP1 and ASXL1 (By similarity). Interacts with RARA, RXRA (PubMed:16606617). Interacts with NCOA1 (By similarity). Interacts with PPARA and PPARG (PubMed:21047783).|||Contains two Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which may be required for an association with nuclear receptors.|||Nucleus|||Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG) (PubMed:16606617). Acts as a coactivator of RARA and RXRA through association with NCOA1 (PubMed:16606617). Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity (PubMed:21047783). Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (By similarity). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing (By similarity).|||The HARE HTH-type domain recognizes and binds N(6)-methyladenosine methylated DNA (m6A).|||Ubiquitinated by TRIP12, leading to its subsequent degradation following binding N(6)-methyladenosine methylated DNA (m6A).|||Was reported to act as a corepressor through recruitment of KDM1A and CBX; this publication has been retracted. http://togogenome.org/gene/10090:Msl2 ^@ http://purl.uniprot.org/uniprot/Q69ZF8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the MSL2 family.|||Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the KAT8/MOF/MYST1, MSL1/hampin, MSL2 and MSL3. Forms a MSL heterotetrameric core with MSL1.|||Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure (By similarity). Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histone H3 methylation at 'Lys-5' (H3K4me) and 'Lys-80' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (By similarity). http://togogenome.org/gene/10090:Ggta1 ^@ http://purl.uniprot.org/uniprot/P23336|||http://purl.uniprot.org/uniprot/Q3TXW0|||http://purl.uniprot.org/uniprot/Q8C2H7|||http://purl.uniprot.org/uniprot/Q91W00|||http://purl.uniprot.org/uniprot/Q9DBU1 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Golgi stack membrane|||Membrane|||Synthesizes the galactose-alpha(1,3)-galactose group by catalyzing the transfer of a galactose residue, with an alpha-1,3 linkage, on terminal lactosaminide (Gal-beta-1,4-GlcNAc-R) disaccharide borne by a glycoprotein or a glycolipid. Preferentially glycosylates proteins, can synthesize galactose-alpha(1,3)-galactose on glycoproteins but cannot synthesize the glycolipid called isoglobotrihexosylceramide or isogloboside 3 (iGb3).|||The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis. http://togogenome.org/gene/10090:Or2h2c ^@ http://purl.uniprot.org/uniprot/L7N475 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zcchc9 ^@ http://purl.uniprot.org/uniprot/Q8R1J3 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in brain cortex and in testis.|||May down-regulate transcription mediated by NF-kappa-B and the serum response element.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Rps27a ^@ http://purl.uniprot.org/uniprot/P62983|||http://purl.uniprot.org/uniprot/Q642L7 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Component of the 40S subunit of the ribosome (PubMed:19754430). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.|||In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.|||In the N-terminal section; belongs to the ubiquitin family.|||Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.|||Monoubiquitinated at Lys-107 and Lys-113 by RNF25 in response to ribosome collisions (ribosome stalling): ubiquitination promotes subsequent activation of RNF14, leading to EEF1A1 ubiquitination and degradation and rescue of stalled ribosomes. Deubiquitination at Lys-113 by USP16 is required for maturation of the 40S ribosomal complex.|||Nucleus|||Part of the 40S ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30.|||Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.|||nucleolus http://togogenome.org/gene/10090:Pramel36 ^@ http://purl.uniprot.org/uniprot/J3QMM8 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Actr2 ^@ http://purl.uniprot.org/uniprot/P61161|||http://purl.uniprot.org/uniprot/Q5SW83 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with bacterium B.thailandensis BimA.|||ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. Seems to contact the pointed end of the daughter actin filament. In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Belongs to the actin family.|||Belongs to the actin family. ARP2 subfamily.|||Cell projection|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. Interacts with AVIL.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Kcnk10 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VJZ9|||http://purl.uniprot.org/uniprot/F6YU65|||http://purl.uniprot.org/uniprot/Q3LS20|||http://purl.uniprot.org/uniprot/Q8BUW1|||http://purl.uniprot.org/uniprot/Q8BZB0|||http://purl.uniprot.org/uniprot/Q9CX88 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Membrane http://togogenome.org/gene/10090:Sry ^@ http://purl.uniprot.org/uniprot/Q05738 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-81 contributes to its nuclear localization and enhances its interaction with KPNB1.|||Belongs to the SRY family.|||Constitutes a minor isoform, which is unstable due to the presence of a degron at the C-terminus that promotes its degradation (PubMed:33004521). Not necessary and sufficient for initiating male sex determination (PubMed:33004521).|||Constitutes the major isoform, which is necessary and sufficient for initiating male sex determination.|||Cytoplasm|||DNA binding and bending properties of the HMG domains of mouse and human SRY differ form each other. Mouse SRY shows less extensive minor groove contacts with DNA and a higher specificity of sequence recognition than human SRY.|||Degraded due to the presence of a degron at the C-terminus that promotes its degradation.|||Different alleles occur in strains of Mus musculus (molossinus or domesticus). In particular the poly-Gln region in 167-177 is polymorphic with either 11, 12 or 13 Gln. The nature of this poly-Gln tract could affect the protein's function by disturbing its secondary structure, perhaps by preventing efficient contact with another protein.|||Expressed in gonadal somatic pre-Sertoli cells (PubMed:11784049, PubMed:16904257, PubMed:7600978, PubMed:7670499). Expressed in the substantia nigra of the brain (at protein level). Expressed in diencephalon, cortex, the substantia nigra of the midbrain and the medial mammillary bodies of the hypothalamus of male, but not female.|||Expressed in gonadal somatic pre-Sertoli cells (PubMed:33004521). While it is expressed at lower level compared to isoform Sry-S, this form is more stable and constitutes the predominant protein product of the Sry locus in XY gonads (at protein level) (PubMed:33004521).|||Expressed in gonadal somatic pre-Sertoli cells from 10.5 to 11.5 dpc. Expressed in pre-Sertoli cells located centrally in the genital ridge and then later in cells located at the cranial and caudal poles (at protein level).|||Interacts with KPNB1, ZNF208 isoform KRAB-O, PARP1 and SLC9A3R2 (PubMed:11535586, PubMed:15469996, PubMed:16166090, PubMed:16904257). The interaction with KPNB1 is sensitive to dissociation by Ran in the GTP-bound form (PubMed:11535586). Interaction with PARP1 impaired its DNA-binding activity (PubMed:16904257). Interacts with CALM, EP300, HDAC3 and WT1 (By similarity). The interaction with EP300 modulates its DNA-binding activity (By similarity).|||Nucleus|||Nucleus speckle|||Phosphorylated on serine residues by PKA (By similarity). Phosphorylation by PKA enhances its DNA-binding activity and stimulates transcription repression (By similarity).|||Poly-ADP-ribosylated by PARP1 (PubMed:16904257). ADP-ribosylation reduces its DNA-binding activity (PubMed:16904257).|||SRY protein has long been thought to be encoded by a single exon, coding for Sry-S (PubMed:33004521). However, in addition to the isoform coded by a single exon, Sry-S, an isoform harboring an additional exon, isoform Sry-T, was identified (PubMed:33004521). Isoform Sry-T constitues the major isoform, as isoform Sry-S is unstable due to the presence of the degron at the C-terminus (PubMed:33004521).|||Specific deletion of isoform Sry-T in XY mice results in complete male-to-female sex reversal.|||Transcriptional regulator that controls a genetic switch in male development (PubMed:33004521). It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (PubMed:33004521). Involved in different aspects of gene regulation including promoter activation or repression (PubMed:8190643, PubMed:8159753, PubMed:15170344). Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3' (PubMed:8190643, PubMed:8159753, PubMed:15170344). SRY HMG box recognizes DNA by partial intercalation in the minor groove and promotes DNA bending (PubMed:8190643, PubMed:8159753, PubMed:15170344). Also involved in pre-mRNA splicing (By similarity). In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity). http://togogenome.org/gene/10090:Or1j15 ^@ http://purl.uniprot.org/uniprot/Q8VFP9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Garin5a ^@ http://purl.uniprot.org/uniprot/A1L3C1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GARIN family.|||Detected in testis at 28 days after birth and expression is maintained (PubMed:28742876). Expressed by testicular cells and testicular sperm but not mature sperm (PubMed:28742876).|||Expressed in testis (at protein level).|||Golgi apparatus|||Interacts (via N-terminus) with RAB2B (in GTP-bound form).|||RAB2B effector protein which promotes cytosolic DNA-induced innate immune responses. Regulates IFN responses against DNA viruses by regulating the CGAS-STING signaling axis. http://togogenome.org/gene/10090:Rad23a ^@ http://purl.uniprot.org/uniprot/P54726|||http://purl.uniprot.org/uniprot/Q3TN85|||http://purl.uniprot.org/uniprot/Q8CAP3 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAD23 family.|||Cytoplasm|||Interacts with XPC; the interaction is suggesting the existence of a functional equivalent variant XPC complex. Interacts with PSMD4 and PSMC5. Interacts with ATXN3. Interacts with UBQLN2 (By similarity).|||Involved in nucleotide excision repair and is thought to be functional equivalent for Rad23b in global genome nucleotide excision repair (GG-NER) by association with Xpc. In vitro, the XPC:RAD23A dimer has NER activity. Can stabilize Xpc. Reported differences to Rad23b in regard to NER activity and Xpc stabilization are probably due to differences in expression levels with Rad23a being much less expressed than Rad23b.|||Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin chains in a length-dependent manner and with a lower affinity to 'Lys-63'-linked polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome (By similarity).|||Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Involved in nucleotide excision repair.|||No visible phenotype. Rad23a and Rad23b double knockout is embryonic lethal. Cells show reduced cell survival upopn UV radiation and reduced steady-state level of Xpc indicating a reduced NER capacity.|||Nucleus|||The ubiquitin-like (UBL) and the UBA (ubiquitin-associated) domains interact intramolecularly in a highly dynamic manner, as each UBA domain competes for an overlapping UBL domain surface. Binding of ubiquitin or proteasome subunit Psmd4 disrupt the UBL-UBA domain interactions and drive Rad23a in to an open conformation (By similarity). http://togogenome.org/gene/10090:Rpl5 ^@ http://purl.uniprot.org/uniprot/P47962|||http://purl.uniprot.org/uniprot/Q3TKR5|||http://purl.uniprot.org/uniprot/Q58EU6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL18 family.|||Component of the large ribosomal subunit (LSU) (PubMed:36517592). Part of a LSU subcomplex, the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11 (By similarity). Interacts with NVL in an ATP-dependent manner (By similarity). Interacts with RRP1B (By similarity). Interacts with IPO5, IPO7 and KPNB1; these interactions may be involved in RPL5 nuclear import for the assembly of ribosomal subunits (By similarity). Interacts with RRP1B (By similarity).|||Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (By similarity). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (By similarity). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (By similarity). As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (By similarity). It also couples ribosome biogenesis to p53/TP53 activation (By similarity). As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Mettl14 ^@ http://purl.uniprot.org/uniprot/Q3UIK4 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MT-A70-like family.|||Conditional knockout mice lacking Mettl3 and Mettl14 in germ cells show impaired spermatogenesis, leading to male infertility (PubMed:28914256). Conditional knockout mice lacking Mettl14 in the developing nervous system die by postnatal day 25 due to protracted cell-cycle progression of cortical neural progenitor cells and reduced differentiation of radial glial cells during embryonic cortical neurogenesis (PubMed:28965759).|||Expressed in testis (PubMed:28914256). Highly expressed in radial glial cells during embryonic cortical neurogenesis (PubMed:28965759).|||Heterodimer; heterodimerizes with METTL3 to form an antiparallel heterodimer that constitutes an active methyltransferase (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716).|||Nucleus|||The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis (PubMed:24394384, PubMed:28965759). In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core (By similarity). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing (By similarity). M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (PubMed:24394384). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (PubMed:24394384). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (PubMed:28914256). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (PubMed:28965759).|||The ability of METTL14 to have catalytic activity is unclear and a number of experimental evidence suggests that it has no methyltransferase activity by itself. According to some reports, has some methyltransferase activity in vitro (PubMed:24394384). However, other studies showed that METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. 3D-structure studies showed that METTL14 contains a degenerate active site that is unable to accommodate donor and acceptor substrates. http://togogenome.org/gene/10090:Ptpn14 ^@ http://purl.uniprot.org/uniprot/Q62130 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cytoplasm|||Interacts with FLT4; the interaction is enhanced by stimulation with VEGFC. Interacts (via PPxY motifs) with YAP1 (via WW domains); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional coactivator activity.|||Nucleus|||PTPN14 deficient mice have swelling of the limbs or periorbital edema. These mice also show hyperplasia of lymphatic capillaries of the ears. There is no evidence of choanal atresia or any overtly dysmorphic features.|||Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor.|||Thymus; in cells of both hematopoietic and non-hematopoietic origins.|||Ubiquitinated by the ECS (Elongin BC-CUL2/5-SOCS-box protein)/LRR1 E3 ligase complex and subsequently targeted to proteasomal degradation.|||cytoskeleton http://togogenome.org/gene/10090:Cyb5r1 ^@ http://purl.uniprot.org/uniprot/Q9DB73 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||Membrane|||NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction. http://togogenome.org/gene/10090:Pcsk4 ^@ http://purl.uniprot.org/uniprot/P29121 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S8 family. Furin subfamily.|||Detected only after the 20th day of postnatal development. Mainly expressed in the round spermatids. Expressed mainly in the early stages of spermiogenesis.|||Expressed abundantly in the testis since postnatal Day 16 (PubMed:1372895, PubMed:16371590, PubMed:21302280). In testis, strongly detected in round and elongated spermatids as well as spermatocytes. Also observed in residual bodies engulfed by Sertoli cells at spermatogenic stages VIII and IX (PubMed:16371590). In ovaries, expressed in macrophage-like cells of the ovarian theca, interstitium and corpora lutea (PubMed:11164898).|||Knockout males show impaired fertility (PubMed:9192653). Sperm from mutants exhibit accelerated capacitation, precocious acrosome reaction, reduced binding to egg zona pellucida, and impaired fertilizing ability (PubMed:16371590). They have abnormal acrosome formation during spermatogenesis (PubMed:22357636). Sperm proteins are hyper-tyrosine phosphorylated during capacitation (PubMed:19342015). In females, the percent of successful mating is comparable to that of their PCSK4 +/- female littermates, however the average litter size of the former is half that of the latter. Knockout ovaries treated with gonatropin are generally smaller, less hyperemic and with fewer corpora lutea than wild type. This difference is associated with a 20-fold lower level of circulating progesterone (PubMed:9192653).|||N-glycosylated.|||Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (PubMed:9192653, PubMed:16371590, PubMed:19342015, PubMed:21302280). Also plays a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (By similarity). May also participate in folliculogenesis in the ovaries (PubMed:11164898).|||Synthesized in the endoplasmic reticulum as a zymogen, is matured by autocatalytic cleavage between the prodomain and the catalytic domain.|||The proPCSK4 form interacts with HSPA5; the interaction takes place at the endoplasmic reticulum.|||acrosome membrane http://togogenome.org/gene/10090:Slc25a41 ^@ http://purl.uniprot.org/uniprot/Q8BVN7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Calcium-independent ATP-Mg/Pi exchanger that catalyzes the electroneutral exchange of Mg-ATP or free ADP against an hydrogenphosphate and participates in the net transport of adenine nucleotides across the mitochondria inner membrane.|||Mainly expressed in testis and at lesser levels in brain.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Katna1 ^@ http://purl.uniprot.org/uniprot/E9PZI6 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with KATNB1.|||Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily.|||Can homooligomerize into hexameric rings, which may be promoted by interaction with microtubules. Interacts with KATNB1, which may serve as a targeting subunit. Interacts with ASPM; the katanin complex formation KATNA1:KATNB1 is required for the association of ASPM. Interacts with dynein and NDEL1. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Interacts with KLHL42 (via the kelch domains). Interacts with CUL3; the interaction is enhanced by KLHL42. Interacts with KATNB1 and KATNBL1. Interacts with CAMSAP2 and CAMSAP3; leading to regulate the length of CAMSAP-decorated microtubule stretches.|||Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth.|||Cytoplasm|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Midbody|||Phosphorylation by DYRK2 triggers ubiquitination and subsequent degradation.|||The N-terminus is sufficient for interaction with microtubules, although high affinity binding to microtubules also requires an intact C-terminal domain and ATP, which promotes oligomerization.|||Ubiquitinated by the BCR(KLHL42) E3 ubiquitin ligase complex, leading to its proteasomal degradation. Ubiquitinated by the EDVP E3 ligase complex and subsequently targeted for proteasomal degradation.|||centrosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Klhl7 ^@ http://purl.uniprot.org/uniprot/Q8BUL5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Component of the BCR(KLHL7) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL7 and RBX1 (By similarity).|||Nucleus|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. The BCR(KLHL7) complex acts by mediating ubiquitination and subsequent degradation of substrate proteins. Probably mediates 'Lys-48'-linked ubiquitination (By similarity). http://togogenome.org/gene/10090:Btg3 ^@ http://purl.uniprot.org/uniprot/P50615|||http://purl.uniprot.org/uniprot/Q52L83 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the BTG family.|||Overexpression impairs serum-induced cell cycle progression from the G0/G1 to S phase.|||Ubiquitous. http://togogenome.org/gene/10090:Rev1 ^@ http://purl.uniprot.org/uniprot/Q920Q2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-Y family.|||Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.|||Interacts with FAAP20 (By similarity). Monomer. Interacts with the DNA polymerase zeta which is composed of REV3L and MAD2L2; the interaction with MAD2L2 is direct and requires that REV3L is in its closed conformation. Interacts with POLH, POLI and POLK.|||Nucleus|||The C-terminal domain is necessary for protein interactions.|||Ubiquitous. http://togogenome.org/gene/10090:Cgref1 ^@ http://purl.uniprot.org/uniprot/Q8R1U2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation ^@ Both EF-hands are required for function.|||Mediates cell-cell adhesion in a calcium-dependent manner. Able to inhibit growth in several cell lines (By similarity).|||Probably digested extracellularly by an unknown serine protease generating extremely hydrophobic bioactive peptides.|||Secreted http://togogenome.org/gene/10090:Tbx5 ^@ http://purl.uniprot.org/uniprot/P70326|||http://purl.uniprot.org/uniprot/Q5CZX7 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-339 by KAT2A and KAT2B promotes nuclear retention.|||Cytoplasm|||DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation. Binds to the core DNA motif of NPPA promoter.|||First expressed at day 7.5, exclusively in the allantois. At day 8.5, expressed only in the sinous venosus of the developing heart. At day 9.5, expression observed in the forelimb bud, optic vesicle and sinous venosus. By day 12.5, expression is limited to the retina, the body wall and the mesenchyme of the lung, of the mandible and of that surrounding the trachea.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Monomer. Homodimer (via the T-box); binds DNA as homodimer. Interacts (via the T-box) with NKX2-5 (via the homeobox); this complex binds DNA. Interacts with GATA4. Interacts with KAT2A and KAT2B.|||Nucleus|||The T-Box domain binds to double-stranded DNA. http://togogenome.org/gene/10090:Nupl2 ^@ http://purl.uniprot.org/uniprot/Q8CIC2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Nucleus membrane|||O-glycosylated.|||Probable component of the nuclear pore complex (NPC). Interacts with nuclear export protein NXF1. Interacts with GLE1. Able to form a heterotrimer with NUP155 and GLE1 in vitro (By similarity). Interacts with XPO1 (By similarity).|||Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm.|||The FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC.|||nuclear pore complex http://togogenome.org/gene/10090:Galk2 ^@ http://purl.uniprot.org/uniprot/Q3U3H5|||http://purl.uniprot.org/uniprot/Q68FH4|||http://purl.uniprot.org/uniprot/Q8BUU7 ^@ Function|||Similarity|||Subunit ^@ Acts on GalNAc (By similarity). Also acts as a galactokinase when galactose is present at high concentrations (By similarity).|||Belongs to the GHMP kinase family. GalK subfamily.|||Monomer. http://togogenome.org/gene/10090:Nnmt ^@ http://purl.uniprot.org/uniprot/D3YX59|||http://purl.uniprot.org/uniprot/O55239|||http://purl.uniprot.org/uniprot/Q9D9X3 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.|||Catalyzes the N-methylation of nicotinamide using the universal methyl donor S-adenosyl-L-methionine to form N1-methylnicotinamide and S-adenosyl-L-homocysteine, a predominant nicotinamide/vitamin B3 clearance pathway (PubMed:26168293, PubMed:29483571). Plays a central role in regulating cellular methylation potential, by consuming S-adenosyl-L-methionine and limiting its availability for other methyltransferases (By similarity). Actively mediates genome-wide epigenetic and transcriptional changes through hypomethylation of repressive chromatin marks, such as H3K27me3. In a developmental context, contributes to low levels of the repressive histone marks that characterize pluripotent embryonic stem cell pre-implantation state (By similarity). Acts as a metabolic regulator primarily on white adipose tissue energy expenditure as well as hepatic gluconeogenesis and cholesterol biosynthesis (PubMed:24717514, PubMed:26168293). In white adipocytes, regulates polyamine flux by consuming S-adenosyl-L-methionine which provides for propylamine group in polyamine biosynthesis, whereas by consuming nicotinamide controls NAD(+) levels through the salvage pathway (PubMed:24717514). Via its product N1-methylnicotinamide regulates protein acetylation in hepatocytes, by repressing the ubiquitination and increasing the stability of SIRT1 deacetylase (PubMed:26168293). Can also N-methylate other pyridines structurally related to nicotinamide and play a role in xenobiotic detoxification (By similarity).|||Cytoplasm|||Deiminated by PADI1 and PADI2.|||Expressed in white adipose tissue and liver (at protein level).|||Inhibited by 6-methoxynicotinamide (JBSNF-000088).|||Monomer.|||Up-regulated in white adipose tissue and liver in response to high-fat diet. http://togogenome.org/gene/10090:Rabif ^@ http://purl.uniprot.org/uniprot/Q91X96 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DSS4/MSS4 family.|||Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1, RAB3A and RAB10, but is less active on these proteins than on the SEC4 protein. Might play a general role in vesicular transport (By similarity).|||Interacts with RAB8A. http://togogenome.org/gene/10090:S100a10 ^@ http://purl.uniprot.org/uniprot/P08207 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.|||Belongs to the S-100 family.|||Does not appear to bind calcium. Contains 2 ancestral calcium site related to EF-hand domains that have lost their ability to bind calcium.|||Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36 (By similarity). Interacts with SCN10A (By similarity). Interacts with TASOR (PubMed:31112734). http://togogenome.org/gene/10090:Chd7 ^@ http://purl.uniprot.org/uniprot/A2AJK6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||Expressed in the outflow tract of the heart, optic vesicle, facio-acoustic preganglion complex, brain, olfactory pit, and mandibular component of the first branchial arch.|||May be due to an intron retention.|||May interact with CTCF (By similarity). Interacts with CHD8 (By similarity). Interacts with FAM124B. Found in a complex composed of AGO2, CHD7 and FAM172A (PubMed:29311329). Interacts with TLK2 (By similarity).|||Nucleus|||Probable transcription regulator. Maybe involved in the in 45S precursor rRNA production (By similarity). http://togogenome.org/gene/10090:Ptbp2 ^@ http://purl.uniprot.org/uniprot/Q91Z31 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in whole brain tissues from 11.5 dpc to adulthood.|||Mainly expressed in brain, including cerebellum, brainstem, spinal cord, and hypothalamus. Also expressed in the peripheral nervous system and neural crest derivatives, including the dorsal root and trigeminal ganglia, the cochlear spiral and intestinal ganglion cells, and the adrenal medulla. Also detected to a lower extent in testis, heart, liver, lung, skeletal muscle and thymus (at protein level).|||Monomer. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Part of a ternary complex containing KHSRP and HNRPH1 (By similarity). Interacts with NOVA1; the interaction is direct (PubMed:10829067). Interacts with NOVA2; the interaction is direct (PubMed:10829067).|||Nucleus|||RNA-binding protein which binds to intronic polypyrimidine tracts and mediates negative regulation of exons splicing (PubMed:10829067, PubMed:30638744). May antagonize in a tissue-specific manner the ability of NOVA1 to activate exon selection (PubMed:10829067). In addition to its function in pre-mRNA splicing, also plays a role in the regulation of translation (PubMed:11726525). http://togogenome.org/gene/10090:Hmgn1 ^@ http://purl.uniprot.org/uniprot/P18608|||http://purl.uniprot.org/uniprot/Q8CEW1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HMGN family.|||Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation. Inhibits the phosphorylation of nucleosomal histones H3 and H2A by RPS6KA5/MSK1 and RPS6KA3/RSK2.|||Cytoplasm|||Interacts with transcriptional regulator SEHBP.|||Nucleus|||Phosphorylation favors cytoplasmic localization (By similarity). Phosphorylation on Ser-20 and Ser-24 weakens binding to nucleosomes and increases the rate of H3 phosphorylation. http://togogenome.org/gene/10090:Qsox1 ^@ http://purl.uniprot.org/uniprot/Q8BND5 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the quiescin-sulfhydryl oxidase (QSOX) family.|||Binds 1 FAD per subunit.|||Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide (PubMed:26819240). Plays a role in disulfide bond formation in a variety of extracellular proteins (PubMed:26819240). In fibroblasts, required for normal incorporation of laminin into the extracellular matrix, and thereby for normal cell-cell adhesion and cell migration (PubMed:26819240).|||Detected in skin (at protein level) (PubMed:12354420). Expressed in the seminal vesicles and skin.|||Golgi apparatus membrane|||Monomer.|||N-glycosylated. O-glycosylated on Thr and Ser residues.|||Secreted http://togogenome.org/gene/10090:Rab33b ^@ http://purl.uniprot.org/uniprot/O35963|||http://purl.uniprot.org/uniprot/Q0PD21 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Golgi apparatus membrane|||Interacts with RIC1 (via C-terminus domain); the interaction is direct with a preference for RAB33B-GTP. Interacts with RGP1 (By similarity). Interacts with ATG16L1; the interaction is important for autophagosome formation (PubMed:18448665). Interacts with ATG16L2; however interaction is approximately hundred times lower than for ATG16L1 (PubMed:22082872).|||Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking (By similarity). It is involved in autophagy, acting as a modulator of autophagosome formation.|||Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. In vitro, SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity.|||Ubiquitous.|||cis-Golgi network http://togogenome.org/gene/10090:Syne3 ^@ http://purl.uniprot.org/uniprot/Q4FZC9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Probable anchoring protein which tethers the nucleus to the cytoskeleton by binding PLEC which can associate with the intermediate filament system. Plays a role in the regulation of aortic epithelial cell morphology, and is required for flow-induced centrosome polarization and directional migration in aortic endothelial cells (By similarity).|||Belongs to the nesprin family.|||Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies. Interacts with SUN1 and SUN2; probably forming respective LINC complexes. Interacts with PLEC (via actin-binding domain). Interacts with DST. Interacts with SYNE1. Interacts (via KASH domain) with TOR1A (ATP-bound); the interaction is required for SYNE3 nuclear envelope localization.|||Nucleus envelope|||Nucleus outer membrane|||Rough endoplasmic reticulum|||The KASH domain is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.|||The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.|||Ubiquitous. http://togogenome.org/gene/10090:Or51i1 ^@ http://purl.uniprot.org/uniprot/E9Q7P5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc3a2 ^@ http://purl.uniprot.org/uniprot/P10852 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:9915839, PubMed:10574970, PubMed:11011012, PubMed:10734121). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids. Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (By similarity). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA. SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8. When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation. Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (By similarity).|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the SLC3A transporter family.|||Cell junction|||Cell membrane|||Detected on the surface of embryonic epithelial cells in the epidermis, thymus, kidney, intestine, brain choroid plexus, and in retina. Detected in adult and embryonic brain, spleen, kidney, intestine and liver, and in adult testis (at protein level) (PubMed:9915839). Observed in all adult tissues tested with strongest expression in kidney, small intestine, spleen, thymus and liver (PubMed:9915839). Moderate expression in brain, stomach, heart, testis, lung, skin, pancreas and skeletal muscle. In brain expressed on capillary endothelia in cerebral cortex.|||Disulfide-linked heterodimer with a non-glycosylated light chain (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 or SLC7A11) (PubMed:9915839, PubMed:10574970, PubMed:11011012, PubMed:10734121). Interacts with TLCD3A/CT120 and ICAM1. Constitutively and specifically associates with beta-1 integrins (alpha-2/beta-1, alpha-3/beta-1, alpha-5/beta-1 and alpha-6/beta-1), but minimally with alpha-4/beta-1. Interacts with LAPTM4B; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (By similarity).|||Embryonically lethal between 3.5 and 9.5 dpc.|||Expression induced by concanavalin-A stimulation. Induced during cell activation but is subsequently maintained at constant levels throughout the cell cycle in exponentially growing cells.|||Lysosome membrane|||Melanosome|||N-glycosylated; N-glycosylation is crucial for trafficking and stability of SLC3A2 to the plasma membrane.|||Phosphorylation on Ser-300 or Ser-302 and on Ser-420 by ecto-protein kinases favors heterotypic cell-cell interactions.|||Strong expression in the liver of 14 dpc embryo and in brain, spleen, liver, kidney and intestine of an 18 dpc embryo. http://togogenome.org/gene/10090:Arhgap44 ^@ http://purl.uniprot.org/uniprot/Q5SSM3 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains a PDZ-binding motif at positions 761-764.|||Contains a PDZ-binding motif at positions 767-770.|||GTPase-activating protein (GAP) that stimulates the GTPase activity of Rho-type GTPases. Thereby, controls Rho-type GTPases cycling between their active GTP-bound and inactive GDP-bound states. Acts as a GAP at least for CDC42 and RAC1 (PubMed:24352656, PubMed:26969129). In neurons, is involved in dendritic spine formation and synaptic plasticity in a specific RAC1-GAP activity (PubMed:23739967, PubMed:24352656, PubMed:26969129). Limits the initiation of exploratory dendritic filopodia. Recruited to actin-patches that seed filopodia, binds specifically to plasma membrane sections that are deformed inward by acto-myosin mediated contractile forces. Acts through GAP activity on RAC1 to reduce actin polymerization necessary for filopodia formation (By similarity). In association with SHANK3, promotes GRIA1 exocytosis from recycling endosomes and spine morphological changes associated to long-term potentiation (PubMed:23739967).|||Interacts with BST2 (via cytoplasmic domain).Interacts (probably via PDZ-binding motif) with SHANK3 (via PDZ domain); the interaction takes place in dendritic spines and promotes GRIA1 exocytosis.|||Mutants display a selective and highly significant fear of novel objects and increased stereotypic behavior as well as impairment of motor learning (PubMed:26969129). They show a nicrease in multiple synapses in the hippocampus and cerebellum (PubMed:26969129).|||Presynapse|||Recycling endosome|||Rho-GAP domain is required to promote GRIA1 exocytosis from recycling endosomes. Rho-GAP and BAR domains are necessary for the control of long-term potentiation in hippocampal neurons (PubMed:23739967). In dendrites, BAR domain mediates the recruitment to patches where plasma membrane is deformed by acto-myosin mediated contractile forces (By similarity).|||Specifically expressed in brain (at protein level) (PubMed:26969129). Detected in olfactory bulb, cortex, hippocampus, diencephalon and cerebellum (at protein level) (PubMed:26969129). Expressed in hippocampal neurons (at protein level).|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Ybey ^@ http://purl.uniprot.org/uniprot/Q8CAV0 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the endoribonuclease YbeY family.|||Binds 1 zinc ion.|||Single strand-specific metallo-endoribonuclease involved in rRNA maturation. http://togogenome.org/gene/10090:Cinp ^@ http://purl.uniprot.org/uniprot/Q9D0V8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CINP family.|||Component of the DNA replication complex, which interacts with two kinases, CDK2 and CDC7, thereby providing a functional and physical link between CDK2 and CDC7 during firing of the origins of replication. Regulates ATR-mediated checkpoint signaling in response to DNA damage. Also involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Promotes maturation of pre-60S ribosome together with AFG2A, AFG2B and AIRIM.|||Homodimer. Interacts with CDK2 and CDC7. Interacts with the components of the replication complex, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7 and with ORC2-containing complexes. Interacts with ATRIP. Interacts with CEP152. Associates with pre-60S ribosomal particles. Interacts with AIRIM.|||Nucleus|||Phosphorylated by CDC7 but not by CDK2. http://togogenome.org/gene/10090:Acaa1b ^@ http://purl.uniprot.org/uniprot/Q3UKM0|||http://purl.uniprot.org/uniprot/Q8VCH0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the thiolase-like superfamily. Thiolase family.|||Homodimer. Interacts (via PTS2-type peroxisomal targeting signal region) with PEX7; leading to its translocation into peroxisomes.|||Mainly expressed in liver; weaker levels in kidney, intestine and white adipose tissue.|||Peroxisome|||Responsible for the thiolytic cleavage of straight chain 3-keto fatty acyl-CoAs (3-oxoacyl-CoAs) (Probable). Plays an important role in fatty acid peroxisomal beta-oxidation (Probable). Catalyzes the cleavage of short, medium, long, and very long straight chain 3-oxoacyl-CoAs (By similarity).|||The PTS2-type peroxisomal targeting signal, which mediates interaction with PEX7 and localization to peroxisomes, is cleaved following import into peroxisomes. http://togogenome.org/gene/10090:Or4f15 ^@ http://purl.uniprot.org/uniprot/Q8VF83 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Islr2 ^@ http://purl.uniprot.org/uniprot/Q5RKR3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 11.5 dpc, expressed in spinal nerves, their roots and the ventral spinal cord. At 12.5 dpc, detected in the ventral spinal cord, dorsal root ganglia (DRG), dorsal and ventral roots and sympathetic chain ganglia. At 12.5 dpc, expressed in almost all motor neurons which also express RET and in almost all DRG sensory neurons which also express NTRK1. At 18.5 dpc, expressed only in a subset of NTRK1-expressing neurons but still expressed in nearly all RET-expressing neurons.|||Cell membrane|||Homomultimer. Interacts with NTRK1/TrkA.|||Required for axon extension during neural development.|||Sensory and motor neuron axonal projection defects. http://togogenome.org/gene/10090:Ier5l ^@ http://purl.uniprot.org/uniprot/Q99J55 ^@ Similarity ^@ Belongs to the IER family. http://togogenome.org/gene/10090:Ip6k1 ^@ http://purl.uniprot.org/uniprot/Q6PD10 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the inositol phosphokinase (IPK) family.|||Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.|||Cytoplasm|||Highly expressed in brain and testis. Detected at much lower levels in heart, kidney, liver, lung and spleen.|||Nucleus http://togogenome.org/gene/10090:Nedd4 ^@ http://purl.uniprot.org/uniprot/P46935 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cysteine residue is required for ubiquitin-thioester formation.|||Activated by NDFIP1- and NDFIP2-binding.|||Binds SCNN1A, SCNN1B and SCNN1G. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes. Interacts with UBE2D2 (PubMed:9182527). Binds, in vitro, through the WW2 and WW3 domains, to neural isoforms of ENAH that contain the PPSY motif (PubMed:9407065). Interacts with BEAN1, LITAF, RNF11, WBP1, WBP2, PMEPAI and PRRG2 (PubMed:11042109). Interacts with murine leukemia virus Gag polyprotein (via PPXY motif) (PubMed:15908698). Interacts (via C2 domain) with GRB10 (via SH2 domain) (PubMed:12697834, PubMed:15060076, PubMed:18286479, PubMed:20980250). Interacts with ERBB4 (PubMed:19193720, PubMed:19047365). Interacts with TNIK; the interaction is direct, allows the TNIK-dependent recruitment of RAP2A and its ubiquitination by NEDD4 (PubMed:20159449). Interacts (via WW3 domain) with TNK2; EGF promotes this interaction. Interacts (via WW3 domain) with FGFR1 (via C-terminus). Interacts with OTUD7B (By similarity). Interacts with ISG15 (By similarity). Interacts (via WW domain) with RAPGEF2; this interaction leads to ubiquitination and degradation via the proteasome pathway. Interacts (via WW domains) with ARRDC3 (via PPXY motifs) (By similarity). Interacts with LAPTM4B; may play a role in the lysosomal sorting of LAPTM4B (By similarity). Interacts with ZBTB7B (PubMed:28784777). Interacts with PRRG4 (via cytoplasmic domain) (By similarity). Interacts directly with LDLRAD3; this interaction promotes NEDD4 auto-ubiquitination (By similarity). Interacts with ADRB2 (By similarity). Interacts (via WW domains) with DAZAP2 (via PPAY motif) (By similarity).|||Brain.|||Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Specifically ubiquitinates 'Lys-63' in target proteins (By similarity). Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes (PubMed:18286479). Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19193720). Predominantly involved in ubiquitination of membrane bound forms of ERBB4 rather than processed precursors and intermediate membrane-anchored 80 kDa fragments (m80HER4), with a lesser role in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19047365). Promotes ubiquitination of RAPGEF2. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development (PubMed:20159449). Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (By similarity). Ubiquitinates DAZAP2, leading to its proteasomal degradation (By similarity). Ubiquitinates POLR2A (By similarity). Functions as a platform to recruit USP13 to form an NEDD4-USP13 deubiquitination complex that plays a critical role in cleaving the 'Lys-48'-linked ubiquitin chains of VPS34 and then stabilizing VPS34, thus promoting the formation of autophagosomes (By similarity).|||Lethal during late gestation. Embryos show a retarded development and defects in vasculogenesis and angiogenesis.|||Nucleus|||The WW domains mediate interaction with PPxY motif-containing proteins (By similarity). The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, PMEPAI, NDFIP1 and PRRG2 (PubMed:11042109).|||Undergoes 'Lys-29'-linked auto-ubiquitination at Lys-847 and serves as a scaffold for recruiting USP13 to form an NEDD4-USP13 deubiquitination complex. http://togogenome.org/gene/10090:Otos ^@ http://purl.uniprot.org/uniprot/Q8R448 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the otospiralin family.|||Ear specific.|||May be essential for the survival of the neurosensory epithelium of the inner ear.|||Secreted http://togogenome.org/gene/10090:Epcam ^@ http://purl.uniprot.org/uniprot/Q99JW5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EPCAM family.|||Glycosylation at Asn-198 is crucial for protein stability.|||Lateral cell membrane|||May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E (By similarity).|||Monomer. Interacts with phosphorylated CLDN7 (By similarity).|||tight junction http://togogenome.org/gene/10090:Adra1d ^@ http://purl.uniprot.org/uniprot/A2ANQ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.|||Membrane|||This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium. http://togogenome.org/gene/10090:Cnga3 ^@ http://purl.uniprot.org/uniprot/Q9JJZ8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA3 subfamily.|||Membrane|||Prominently expressed in retina.|||Tetramer formed of three CNGA3 and one CNGB3 modulatory subunits.|||The C-terminal coiled-coil domain mediates homotrimerization of CNGA subunits.|||Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors. Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones (By similarity). Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3. http://togogenome.org/gene/10090:Taf9b ^@ http://purl.uniprot.org/uniprot/A2AP82|||http://purl.uniprot.org/uniprot/Q6NZA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF9 family.|||Binds TAF5 and TAF6. Component of TFIID and the TATA-binding protein-free TAF complex (TFTC). TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Binds N-terminal domain of p53/TP53 which is essential for transcription (By similarity).|||Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or8b1b ^@ http://purl.uniprot.org/uniprot/Q7TRC9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4f47 ^@ http://purl.uniprot.org/uniprot/Q8VF84 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nup214 ^@ http://purl.uniprot.org/uniprot/Q80U93 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited.|||Homodimer. Part of the nuclear pore complex (NPC). Interacts with NUP88. Interacts with ZFP36; this interaction increases upon lipopolysaccharide (LPS) stimulation. Interacts with DDX19. Interacts with XPO1. Interacts with XPO5.|||Part of the nuclear pore complex. Has a critical role in nucleocytoplasmic transport. May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex.|||Probably glycosylated as it reacts with wheat germ agglutinin (WGA).|||The beta-propeller contains long interblade connector loops, and mediates interaction with DDX19B.|||nuclear pore complex http://togogenome.org/gene/10090:Nptx1 ^@ http://purl.uniprot.org/uniprot/A2ACL9|||http://purl.uniprot.org/uniprot/Q3UST4|||http://purl.uniprot.org/uniprot/Q62443 ^@ Caution|||Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 2 calcium ions per subunit.|||Endoplasmic reticulum|||Expressed in brain and kidney.|||Homooligomer or heterooligomer (probably pentamer) with neuronal pentraxin receptor (NPTXR).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be involved in mediating uptake of synaptic material during synapse remodeling or in mediating the synaptic clustering of AMPA glutamate receptors at a subset of excitatory synapses.|||Secreted|||secretory vesicle http://togogenome.org/gene/10090:Gm20902 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Pdcd1lg2 ^@ http://purl.uniprot.org/uniprot/Q9WUL5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Cell membrane|||Expressed in immature and mature bone marrow-derived dendritic cells and splenic dendritic cells. Highly expressed in placenta, liver and weakly expressed in heart, spleen, lymph nodes and thymus. Also expressed in some tumor cell lines of lymphoid origin.|||Interacts with PDCD1.|||Involved in the costimulatory signal essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle progression and cytokine production. http://togogenome.org/gene/10090:Or4f53 ^@ http://purl.uniprot.org/uniprot/Q8VF40 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Emc2 ^@ http://purl.uniprot.org/uniprot/Q6A0D1|||http://purl.uniprot.org/uniprot/Q9CRD2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC2 family.|||Component of the ER membrane protein complex (EMC).|||Component of the ER membrane protein complex (EMC). Interacts with WNK1 (via amphipathic alpha-helix region); promoting the ER membrane protein complex assembly by preventing EMC2 ubiquitination.|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins.|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes.|||Ubiquitinated when soluble in the cytoplasm, leading to its degradation by the proteasome. Interaction with EMC2 prevents its ubiquitination and degradation. http://togogenome.org/gene/10090:Itgb3bp ^@ http://purl.uniprot.org/uniprot/Q9CQ82 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, which is essential for the association with nuclear receptors.|||Expressed in the spermatogonia and spermatocytes.|||Homodimer; mediated by the coiled coil domain. Interacts with CCNA2 and MTA1. Interacts with NFKB1 NF-kappa-B subunit. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (By similarity). Interacts with TASOR (PubMed:31112734).|||Nucleus|||The DD1 domain (also called RepD1 domain) mediates the corepressor function and is essential in the triggering of apoptosis.|||Transcription coregulator that can have both coactivator and corepressor functions. Involved in the coactivation of nuclear receptors for retinoid X (RXRs) and thyroid hormone (TRs) in a ligand-dependent fashion. In contrast, it does not coactivate nuclear receptors for retinoic acid, vitamin D, progesterone receptor, nor glucocorticoid. Acts as a coactivator for estrogen receptor alpha. Acts as a transcriptional corepressor via its interaction with the NFKB1 NF-kappa-B subunit, possibly by interfering with the transactivation domain of NFKB1. Induces apoptosis in breast cancer cells, but not in other cancer cells, via a caspase-2 mediated pathway that involves mitochondrial membrane permeabilization but does not require other caspases. May also act as an inhibitor of cyclin A-associated kinase. Also acts a component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex (By similarity).|||centromere|||kinetochore http://togogenome.org/gene/10090:Ifi44l ^@ http://purl.uniprot.org/uniprot/Q9BDB7 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFI44 family.|||By respiratory syncytial virus/RSV (PubMed:32611756). HA-28 antigen is expressed after induction by inflammatory cytokines.|||Cytoplasm|||Deletion mutants result in elevated respiratory syncycial virus/RSV infection in vitro.|||Expressed on cells of the hematopoietic lineage. Detected in transformed cell lines of the macrophage and B-cell lineage. Expressed in spleen and bone marrow.|||HA-28 antigen forms a complex with Kb MHC in BALB.B donor cells. Interacts with FKBP5; this interaction modulates IKBKB and IKBKE kinase activities (By similarity).|||Precursor of the histocompatibility antigen HA-28 in BALB.B mice. More generally, minor histocompatibility antigens refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD). More specifically, HA-28 minor antigen is transcribed in the BALB.B donor but not in host C57BL/6 cells. HA-28 is presented to the donor BALB.B cell surface by Kb MHC. This complex HA-28/Kb MHC elicits cytotoxic T-cell response in C57BL/6 mice immunized with BALB.B spleen cells. It induces C57BL/6 mice cells recognition and lysis by CD8 T-cell from BALB.B mice.|||Type I interferon-stimulated gene (ISG) that plays a critical role in antiviral and antibacterial activity. During bacterial infection, promotes macrophage differentiation and facilitates inflammatory cytokine secretion (By similarity). Plays a role in the control of respiratory syncycial virus/RSV infection, reducing the ability of the virus to replicate (PubMed:32611756). Acts as a feedback regulator of IFN responses by negatively regulating IKBKB kinase activity through interaction with FKBP5 (By similarity). http://togogenome.org/gene/10090:Fermt2 ^@ http://purl.uniprot.org/uniprot/Q3TLE2|||http://purl.uniprot.org/uniprot/Q8CIB5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the kindlin family.|||Cell surface|||Complete embryonic lethality at peri-implantation stage, due to severe detachment of the endoderm and epiblast from the basement membrane. Heterozygous mice lacking one copy of Fermt2 show no visible phenotype, but show decreased tumor angiogenesis upon transplantation of tumor cells, and their blood vessels are abnormally leaky.|||Cytoplasm|||Detected in adult heart muscle (at protein level). Detected in heart, skeletal muscle and testis.|||I band|||Interacts with ITGB1; the interaction is inhibited in presence of ITGB1BP1. Interacts with FBLIM1. Interacts with active, unphosphorylated CTNNB1. Identified in a complex with CTNNB1 and TCF7L2/TCF4 (By similarity). Interacts with ILK, ITGB1 and ITGB3.|||Membrane|||Nucleus|||Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling.|||The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain.|||The N-terminal region displays a ubiquitin-type fold and mediates interaction with membranes containing negatively charged phosphatidylinositol phosphate via a surface enriched in positively charged residues.|||The PH domain binds phospholipids. Binds preferentially phosphatidylinositol-3,4,5-trisphosphate, and has lower affinity for phosphatidylinositol-4,5-bisphosphate (By similarity).|||cell cortex|||cytoskeleton|||focal adhesion|||lamellipodium membrane|||stress fiber http://togogenome.org/gene/10090:Rab11fip2 ^@ http://purl.uniprot.org/uniprot/G3XA57 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ A Rab11 effector binding preferentially phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and phosphatidic acid (PA) and acting in the regulation of the transport of vesicles from the endosomal recycling compartment (ERC) to the plasma membrane. Involved in insulin granule exocytosis. Also involved in receptor-mediated endocytosis and membrane trafficking of recycling endosomes, probably originating from clathrin-coated vesicles. Required in a complex with MYO5B and RAB11 for the transport of NPC1L1 to the plasma membrane. Also acts as a regulator of cell polarity. Plays an essential role in phagocytosis through a mechanism involving TICAM2, RAC1 and CDC42 Rho GTPases for controlling actin-dynamics.|||Cell membrane|||Homooligomerizes in a Rab11-independent manner. Forms a heterooligomeric complex with RAB11FIP4. Interacts with AP2A1, MYO5B, RAB25 and REPS1. Interacts with RAB11A and RAB11B (activated GTP-bound form). Interacts with NPC1L1. Interacts (via NPF motifs) with EHD1 and EHD3. Interacts with TICAM2; this interaction directs RAB11FIP2 to the phagosome.|||Phosphorylation at Ser-227 by MARK2 regulates epithelial cell polarity.|||Recycling endosome membrane http://togogenome.org/gene/10090:Slc47a2 ^@ http://purl.uniprot.org/uniprot/Q3V050 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.|||Cell membrane|||Expressed in testis; especially in testicular Leydig cells.|||Human SLC47A2/MATE2 and rodent SLC47A2/MATE2 exhibit only low mutual sequence identity (38.1%) and different expression patterns. In fact, the counterparts of human SLC47A2/MATE2 have not been identified in rats and mice, and the counterpart of rodent SLC47A2/MATE2 has not been found in humans. The phylogenetic tree of mammalian MATE-type transporters clearly suggested that rodent SLC47A2/MATE2 would be classified into an new subgroup:SLC47A3/MATE3 family but not SLC47A2/MATE2 family. As the nomenclature and classification are confusing, PubMed:17715386 suggested to rename mouse and rat SLC47A2/MATE2 to SLC47A3/MATE3.|||Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:17715386). May mediate testosterone efflux from the Leydig cells in the testes (PubMed:17715386). http://togogenome.org/gene/10090:Eea1 ^@ http://purl.uniprot.org/uniprot/Q8BL66 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in endosomal trafficking.|||Cytoplasm|||Early endosome membrane|||Homodimer. Binds STX6. Binds RAB5A, RAB5B, RAB5C and RAB22A that have been activated by GTP-binding. Interacts with ERBB2 (By similarity). Interacts with RAB31. Interacts with SAMD9 and SAMD9L (By similarity). May interact with PLEKHF2 (By similarity).|||The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions (By similarity). http://togogenome.org/gene/10090:Pdia4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Z1|||http://purl.uniprot.org/uniprot/P08003 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum lumen|||Melanosome|||Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Component of a complex containing at least CRELD2, MANF, MATN3 and PDIA4 (PubMed:23956175).|||Part of a large chaperone multiprotein complex. http://togogenome.org/gene/10090:Cyp7b1 ^@ http://purl.uniprot.org/uniprot/Q3USU4|||http://purl.uniprot.org/uniprot/Q60991 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of endogenous oxysterols and steroid hormones, including neurosteroids (PubMed:9295351, PubMed:9144166, PubMed:10748047, PubMed:11067870). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of steroids with a preference for 7-alpha position. Usually metabolizes steroids carrying a hydroxy group at position 3, functioning as a 3-hydroxy steroid 7-alpha hydroxylase (PubMed:9295351, PubMed:9144166, PubMed:10748047, PubMed:11067870). Hydroxylates oxysterols, including 25-hydroxycholesterol and (25R)-cholest-5-ene-3beta,26-diol toward 7-alpha hydroxy derivatives, which may be transported to the liver and converted to bile acids (PubMed:9295351, PubMed:9144166, PubMed:10748047, PubMed:11067870). Via its product 7-alpha,25-dihydroxycholesterol, a ligand for the chemotactic G protein-coupled receptor GPR183/EBI2, regulates B cell migration in germinal centers of lymphoid organs, thus guiding efficient maturation of plasma B cells and overall antigen-specific humoral immune response (PubMed:22999953). 7-alpha hydroxylates neurosteroids, including 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) and pregnenolone, both involved in hippocampus-associated memory and learning (PubMed:9144166). Metabolizes androstanoids toward 6- or 7-alpha hydroxy derivatives (By similarity).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highly expressed in brain structures including the corpus callosum, the anterior commissure and fornix (PubMed:8530364). The hippocampal expression is particularly prominent in the dentate gyrus (PubMed:8530364). Expressed in liver and kidney. The hepatic expression is sexually dimorphic, predominantly detected in male liver while barely detectable in females (PubMed:8530364). Expressed in lymph nodes and spleens, in both lymphoid and stromal compartments (PubMed:22999953). Higher expression is detected in fibroblastic reticular cells, a type of stromal cells in the lymph nodes (PubMed:22999953). Also expressed at high levels in the outer follicle and at the B cell-T cell boundary of splenic germinal centers (PubMed:22999953). Expressed in dendritic cells (DCs) subpopulations being most abundant in CD8-positive DCs (PubMed:22999953).|||Inhibited by drugs voriconazole and metyrapone.|||Knockout mice exhibit impaired generation of plasma cells and overall deficient antigen-specific humoral immune response.|||Microsome membrane http://togogenome.org/gene/10090:Pithd1 ^@ http://purl.uniprot.org/uniprot/Q8BWR2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PITHD1 family.|||Cytoplasm|||Promotes megakaryocyte differentiation by up-regulating RUNX1 expression (PubMed:25134913). Regulates RUNX1 expression by activating the proximal promoter of the RUNX1 gene and by enhancing the translation activity of an internal ribosome entry site (IRES) element in the RUNX1 gene (By similarity). http://togogenome.org/gene/10090:Suox ^@ http://purl.uniprot.org/uniprot/Q8R086 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group non-covalently per subunit.|||Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.|||Homodimer.|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Tm9sf3 ^@ http://purl.uniprot.org/uniprot/Q9ET30 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.|||Membrane http://togogenome.org/gene/10090:Pwwp3a ^@ http://purl.uniprot.org/uniprot/Q6DID5 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PWWP3A family.|||Interacts with TP53BP1 (via BRCT domain); the interaction is not dependent on its phosphorylation status. Binds nucleosomes. Interacts with trimethylated 'Lys-36' of histone H3 (H3K36me3) (in vitro) (By similarity).|||Intron retention. This sequence is incomplete at the 5'-end.|||Involved in the DNA damage response pathway by contributing to the maintenance of chromatin architecture. Recruited to the vicinity of DNA breaks by TP53BP1 and plays an accessory role to facilitate damage-induced chromatin changes and promoting chromatin relaxation. Required for efficient DNA repair and cell survival following DNA damage (By similarity).|||Nucleus|||The PWWP domain mediates the interaction with nucleosomes. http://togogenome.org/gene/10090:Usp54 ^@ http://purl.uniprot.org/uniprot/Q8BL06 ^@ Caution|||Function|||Similarity ^@ Although the active site residues are conserved, lacks the conserved His residue which is normally found 9 residues before the catalytic His.|||Belongs to the peptidase C19 family.|||Has no peptidase activity. http://togogenome.org/gene/10090:Tmed10 ^@ http://purl.uniprot.org/uniprot/Q9D1D4 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMP24/GP25L family.|||Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi. The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes. Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side. Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles. In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (By similarity). Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment. Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (By similarity). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (By similarity). On Golgi membranes, acts as primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation. Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus. Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization. In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC. Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9. Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (By similarity).|||Cell membrane|||Early embryonic lethal. Decreases the protein but not the mRNA level of Tmed3 and Tmed9. Heterozygous Tmed10 +/- mice are viable but show structural deficits in the Golgi morphology, such as the formation of dilated saccules (PubMed:10660306). Conditional knockout mice show a increase in serum interleukin-1 beta (IL1B) and inflammation levels (PubMed:32272059).|||Ectopic expression of TMED10 alone does not result in its proper cis-Golgi network localization. Interaction of TMED10 with TMED2 is both necessary and sufficient for transport of the couple to the cis-Golgi network, and TMED3 and/or TMED9 contribute to facilitating the process.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||Melanosome|||Predominantly dimeric and to a lesser extent monomeric in the ER. Monomer and dimer in ERGIC and cis-Golgi network. Forms homooligomer (via GOLD domain); the assembly is promoted by direct binding with leaderless cargos and may form a protein channel that facilitates cargo entry into the ERGIC. Forms heterooligomeric complexes with other members of the p24 family such as TMED2, TMED7 and TMED9. Interacts (via GOLD domain) with TMED2 (via GOLD domain); the complex is required for export of TMED10 from the ER to the cis-Golgi network; the complex is proposed to be involved in cis-Golgi network dynamics and / or biogenesis. Associates with the COPI vesicle coat subunits (coatomer) (By similarity). Tetramerization of the cytoplasmic domain at the Golgi membrane in vitro; the complex is proposed to interact with COPI coatomer and induce budding of the vesicles (By similarity). Interacts with COPG1; the interaction involves TMED10 homodimer. Interacts with ARF1 (GDP-bound); the interaction probably involves a TMED10 oligomer. Interacts with SEC23A, SEC24B, SEC24C and SEC24D components of the coat protein complex II/COPII, indicative of an association of TMED10 with the COPII vesicle coat. Interacts with CD59. Interacts with MPPE1/PGAP5; the complex might recruit and sort GPI-anchored proteins to the ER-exit site, or the interaction might lead to recycling of PGAP5 between the ER and the Golgi. Interacts with F2LR1/PAR2 (By similarity). Interacts with KDELR2/ERD2; the interaction is disrupted by KDELR2 ligand (By similarity). Found in a complex composed at least of SURF4, TMED2 and TMED10. Associates with the presenilin-dependent gamma-secretase complex. Interacts with STX17; the interaction is direct. Interacts with IL-1; the interaction is direct. Interacts with RAB21 (active GTP-bound form); the interaction is indirect and regulates TMED10 abundance and localization at the Golgi (By similarity).|||The GOLD domain is required for proper p24 heterooligomeric complex formation and efficient transport of GPI-anchored proteins.|||The lumenal domain mediates localization to the plasma membrane by partially overriding the ER retention by the cytoplasmic domain.|||cis-Golgi network membrane|||secretory vesicle membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Vmn1r183 ^@ http://purl.uniprot.org/uniprot/Q8K3N5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tfap2b ^@ http://purl.uniprot.org/uniprot/E9Q5N4|||http://purl.uniprot.org/uniprot/Q61313|||http://purl.uniprot.org/uniprot/Q8CCV4|||http://purl.uniprot.org/uniprot/Q8CE69 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AP-2 family.|||Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with CITED4. Interacts with UBE2I. Interacts with KCTD1; this interaction represses transcription activation. Interacts with CITED2 (via C-terminus); the interaction stimulates TFAP2B-transcriptional activity (By similarity).|||During retinoic acid-mediated differentiation. Up-regulated by starvation and a high fat diet (PubMed:25187989).|||Expressed from embryo day 9.5 to birth. In day 13.5 embryo, expressed abundantly in cells coating the neural tube. Expression continues posteriorly in the spinal cord, the dorsal root ganglia, in the prevertebal sympathic ganglia and the ganglion nodosum. High expression found in the dorsal and anteriolateral primordium of the midbrain. Expression also found in skin, kidneys and in many areas of the facial mesenchyme. In adults, expressed in the eye, skin, kidney, prostate, thymus, skeletal muscle and, very weakly in the brain. Highest levels found in kidney.|||Localizes to neurons in areas of the cerebral cortex, cerebellum and hypothalamus (at protein level).|||Nucleus|||Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-beta appears to be required for normal face and limb development and for proper terminal differentiation and function of renal tubular epithelia.|||Sumoylated (PubMed:25187989). Sumoylated on Lys-21; which inhibits transcriptional activity (By similarity). http://togogenome.org/gene/10090:Umod ^@ http://purl.uniprot.org/uniprot/Q91X17 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Detected in urine (secreted form). Detected in kidney thick ascending limb epithelial cells (at protein level).|||Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure that may play a role in the water barrier permeability. May serve as a receptor for binding and endocytosis of cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across renal epithelia.|||Homodimer that then polymerizes into long filaments (PubMed:26673890). The filaments can additionally assemble laterally to form a sheet (By similarity). The filaments consist of a zigzag-shaped backbone with laterally protruding arms which interact with bacterial adhesin fimH (By similarity). Two fimH molecules can bind to a single UMOD monomer (By similarity).|||In the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes and inhibits formation of liquid containing supersaturated salts and subsequent formation of salt crystals (PubMed:14871399, PubMed:15327412). Protects against urinary tract infections by binding to type 1 fimbriated E.coli (PubMed:11134021). Binds to the bacterial adhesin fimH which mediates the stable formation of bacterial aggregates, prevents the binding of E.coli to uroplakins UPK1A and UPK1B which act as urothelial receptors for type I fimbriae, and allows for pathogen clearance through micturation (By similarity). Also promotes aggregation of other bacteria including K.pneumoniae, P.aeruginosa and S.mitis and so may also protect against other uropathogens (By similarity).|||Mice suffer significantly more frequently from urinary tract infections. They shown also spontaneous formation of calcium crystals in adult kidneys, and excessive intake of calcium and oxalate dramatically increases both the frequency and the severity of renal calcium crystal formation in mutant mice, but not in wild-type mice.|||N-glycosylated.|||Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found in urine (PubMed:18375198). This cleavage is catalyzed by HPN (PubMed:26673890).|||Secreted|||The ZP domain mediates polymerization, leading to the formation of long filaments (PubMed:12021773, PubMed:26673890). The core of the filament consists of interlocked ZP domains which assemble into a helical structure. Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit. The heavily glycosylated N-terminal part of the protein (containing several EGF-like domains) forms branches which protrude from the core and are be involved in pathogen capture (By similarity).|||cilium membrane http://togogenome.org/gene/10090:Znrf2 ^@ http://purl.uniprot.org/uniprot/Q71FD5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that plays a role in the establishment and maintenance of neuronal transmission and plasticity. Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation. Acts also as a positive regulator of mTORC1 activation by amino acids, which functions upstream of the V-ATPase and of Rag-GTPases. In turn, phosphorylation by mTOR leads to its inhibition via targeting to the cytosol allowing a self-regulating feedback mechanism.|||Endosome membrane|||Expressed primarily in the nervous system. Expression is more intense in the granular cell layer of hippocampus, Purkinje cell layer of the cerebellum and the granular cell layer of the olfactory bulb. Detected in sensory neurons but not expressed in sympatic or enteric neurons. Expressed in testis, adipose tissue, columnar epithelial cells of the gut.|||Interacts with UBE2N. Interacts with ZNRF1. Interacts (when phosphorylated) with YWHAE.|||Lysosome membrane|||Phosphorylated; leading to binding to YWHAE. Phosphorylated by MTOR at Ser-147 and dephosphorylated by PP6C. Ser-147 phosphorylation stimulates vesicle-to-cytosol translocation.|||Presynaptic cell membrane|||The RING-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Dnmt3l ^@ http://purl.uniprot.org/uniprot/A3EWM2|||http://purl.uniprot.org/uniprot/Q9CWR8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Catalytically inactive regulatory factor of DNA methyltransferases that can either promote or inhibit DNA methylation depending on the context (PubMed:11719692, PubMed:15318244, PubMed:15671018, PubMed:24074865). Essential for the function of DNMT3A and DNMT3B: activates DNMT3A and DNMT3B by binding to their catalytic domain (PubMed:15671018). Acts by accelerating the binding of DNA and S-adenosyl-L-methionine (AdoMet) to the methyltransferases and dissociates from the complex after DNA binding to the methyltransferases (PubMed:15671018). Recognizes unmethylated histone H3 lysine 4 (H3K4me0) and induces de novo DNA methylation by recruitment or activation of DNMT3 (By similarity). Plays a key role in embryonic stem cells and germ cells (PubMed:11719692, PubMed:15318244, PubMed:24074865). In germ cells, required for the methylation of imprinted loci together with DNMT3A (PubMed:11719692). In male germ cells, specifically required to methylate retrotransposons, preventing their mobilization (PubMed:15318244). Plays a key role in embryonic stem cells (ESCs) by acting both as an positive and negative regulator of DNA methylation (PubMed:24074865). While it promotes DNA methylation of housekeeping genes together with DNMT3A and DNMT3B, it also acts as an inhibitor of DNA methylation at the promoter of bivalent genes (PubMed:24074865). Interacts with the EZH2 component of the PRC2/EED-EZH2 complex, preventing interaction of DNMT3A and DNMT3B with the PRC2/EED-EZH2 complex, leading to maintain low methylation levels at the promoters of bivalent genes (PubMed:24074865). Promotes differentiation of ESCs into primordial germ cells by inhibiting DNA methylation at the promoter of RHOX5, thereby activating its expression (PubMed:24074865).|||Expressed in testis, thymus, ovary, and heart (PubMed:11306809).|||Homodimer (By similarity). Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (By similarity). Interacts with histone H3 (via N-terminus); interaction is strongly inhibited by methylation at lysine 4 (H3K4me) (By similarity). Interacts with EZH2; the interaction is direct (PubMed:24074865). Interacts with SPOCD1 (PubMed:32674113).|||In testis, first observed in non-dividing prospermatogonia after 12.5 dpc and is highest at about the time of birth; expression declines rapidly after birth and is extinguished by 6 days post partum, when most prospermatogonia have differentiated into dividing spermatogonial stem cells (PubMed:15318244).|||Nucleus|||Oogenesis in female mice takes place normally, but the heterozygous offspring of homozygous mutant females die before mid-gestation due to biallelic expression of imprinted genes normally methylated and silenced on the allele of maternal origin (PubMed:11719692). Male mice are viable but sterile, with a complete absence of germ cells in adult males (PubMed:11719692). Spermatocytes show asynapsis or abnormal synapsis, and do not progress to the full pachytene stage due to demethylation of methylation of both long-terminal-repeat (LTR) and non-LTR retrotransposons (PubMed:15318244). http://togogenome.org/gene/10090:Cir1 ^@ http://purl.uniprot.org/uniprot/Q9DA19 ^@ Function|||Miscellaneous|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Interacts with RP9, SNW1, SFRS1, SFRS2,U2AF1, RBPJ, SAP30, HDAC2 NKAP and NEK6. Interacts with Epstein-Barr virus RPMS1. Component of the histone deacetylase complex. Component of the Notch corepressor complex. Interacts with NKAPL (PubMed:25875095).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus speckle|||Phosphorylated by NEK6.|||Regulates transcription and acts as corepressor for RBPJ. Recruits RBPJ to the Sin3-histone deacetylase complex (HDAC). Required for RBPJ-mediated repression of transcription (By similarity). May modulate splice site selection during alternative splicing of pre-mRNAs.|||centrosome http://togogenome.org/gene/10090:Msto1 ^@ http://purl.uniprot.org/uniprot/E9PUB7|||http://purl.uniprot.org/uniprot/Q2YDW2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the misato family.|||Cytoplasm|||Involved in the regulation of mitochondrial distribution and morphology. Required for mitochondrial fusion and mitochondrial network formation.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Cachd1 ^@ http://purl.uniprot.org/uniprot/Q6PDJ1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calcium channel subunit alpha-2/delta family.|||May regulate voltage-dependent calcium channels.|||Membrane http://togogenome.org/gene/10090:Foxc1 ^@ http://purl.uniprot.org/uniprot/Q61572 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development (PubMed:9635428, PubMed:9106663, PubMed:10479458, PubMed:10395790, PubMed:11562355, PubMed:18187037, PubMed:19668217, PubMed:22493429, PubMed:24590069, PubMed:25808752, PubMed:28223138). Acts either as a transcriptional activator or repressor (PubMed:28223138). Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes (PubMed:25808752). Upon DNA-binding, promotes DNA bending. Acts as a transcriptional coactivator (PubMed:25808752). Stimulates Indian hedgehog (Ihh)-induced target gene expression mediated by the transcription factor GLI2, and hence regulates endochondral ossification (PubMed:25808752). Acts also as a transcriptional coregulator by increasing DNA-binding capacity of GLI2 in breast cancer cells. Regulates FOXO1 through binding to a conserved element, 5'-GTAAACAAA-3' in its promoter region, implicating FOXC1 as an important regulator of cell viability and resistance to oxidative stress in the eye (By similarity). Cooperates with transcription factor FOXC2 in regulating expression of genes that maintain podocyte integrity (PubMed:28223138). Promotes cell growth inhibition by stopping the cell cycle in the G1 phase through TGFB1-mediated signals. Involved in epithelial-mesenchymal transition (EMT) induction by increasing cell proliferation, migration and invasion (By similarity). Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (PubMed:18187037). Plays a role in the gene regulatory network essential for epidermal keratinocyte terminal differentiation (By similarity). Essential developmental transcriptional factor required for mesoderm-derived tissues formation, such as the somites, skin, bone and cartilage (PubMed:9106663, PubMed:10479458, PubMed:10395790, PubMed:10704385, PubMed:11562355, PubMed:15196959). Positively regulates CXCL12 and stem cell factor expression in bone marrow mesenchymal progenitor cells, and hence plays a role in the development and maintenance of mesenchymal niches for haematopoietic stem and progenitor cells (HSPC) (PubMed:24590069). Plays a role in corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner (PubMed:22171010). May function as a tumor suppressor (By similarity).|||Embryos die pre- and perinatally with haemorrhagic hydrocephalus and calvarial defects, beginning at 13.5 dpc (PubMed:9635428, PubMed:10479458, PubMed:19668217). Mutants that survive to later stages exhibit multiple craniofacial and vertebral defects characterized by disorganized rib fusion, absence of chondrocytes proliferation and ossification (PubMed:9106663, PubMed:25808752). Show abnormal cerebellar development with an enlarged fourth ventricle roof plate at 12.5 dpc and a disorganized cerebellar rhombic lip (PubMed:19668217). Show eye formation abnormalities: the lens remains attached to the cornea, both the anterior chamber and the corneal endothelium are absent, the corneal stroma is thicker, the arrangement of mesenchyme cells are disorganized and the corneal endothelial cells do not differentiate (PubMed:10395790). Show cardiovascular defects including persistent truncus arteriosus, ventricular septal defect, coarctation of the aortic arch, and aortic and pulmonary valve dysplasia (PubMed:10479458). Show abnormal kidney and ureter development, including duplex kidneys connecting to double ureters (PubMed:10704385). Show a decrease in hedgehog-induced genes expression levels involved in endochondral ossification (PubMed:25808752). Double knockout of FOXC1 and FOXC2 genes in mice embryos die around 8-9.5 dpc and show profound abnormalities in the first and second branchial arches, the early remodeling of blood vessels, a complete absence of segmented paraxial mesoderm, and the presence of ectopic and disorganized mesonephric kidney tubules (PubMed:11562355, PubMed:15196959). Mice with conditional knockout of both FOXC1 and FOXC2 genes in adult mice show renal tubular damage with protein reabsorption droplets, tubular dilation and proteinaceous casts and show also altered expression levels for several genes involved in the differentiation of podocytes (PubMed:28223138). Display also podocyte degeneration characterized with microvillous transformation, podocyte foot process effacement and irregular thickness of the glomerular basement membrane (PubMed:28223138). Podocyte-cell-specific conditional knockout of both FOXC1 and FOXC2 genes in adult mice show reabsorption droplets, tubular dilation and proteinaceous casts (PubMed:28223138). Endothelial-specific conditional knockout mice show a significant reduction in CXCR4 expression as well as in chemokine CXCL12-induced endothelial cell migration (PubMed:18187037). Limb bud mesenchymal-specific conditional knockout mice display strong reduction in haematopoietic stem and progenitor cells, the presence of adipocytes in marrow cavities (yellow adipose marrow) instead of CXCL12-abundant reticular (CAR) cells and die around 6 weeks of age with haemorrhagic hydrocephalus and calvarial defects (PubMed:24590069). CAR cell-specific conditional knockout mice are viable and die without hydrocephalus defects, but show a reduction in haematopoietic stem and progenitor cells (HSPCs) and most marrow cavities are filled with adipocytes (PubMed:24590069). Adult widespread cell-specific conditional knockout mice show a reduction in haematopoietic stem and progenitor cells (HSPCs), with only occasional adipocytes present in marrow cavities (PubMed:24590069). Neural crest (NC)-specific conditional knockout mice die postnatally with hydrocephalus and craniofacial abnormalities comparable to those seen in conventional knockout mice; embryos display pupillary abnormalities, with impaired collagen formation in the corneal stroma and aberrant vessel growth in the normally avascular corneas (PubMed:22171010).|||Expressed in glomerular epithelial cells, the podocytes (PubMed:28223138). Expressed in a population of adipo-osteogenic progenitor cells, termed CXCL12-abundant reticular (CAR) cells (at protein level) (PubMed:24590069). Expressed in many embryonic tissues, including prechondrogenic mesenchyme, periocular mesenchyme, meninges, endothelial cells and kidney (PubMed:9767123). Detected in adult brain, heart, kidney, adrenal gland, lung and testis, with lower levels in stomach, spleen and thymus (PubMed:9767123). Expressed in endothelial cells (PubMed:18187037). Expressed in the mesenchyme adjacent to the developing cerebellum (PubMed:19668217). Expressed in the sternum and rib cartilage (PubMed:25808752). Expressed in growth plate chondrocytes (PubMed:25808752).|||Expressed in the anterior presomitic mesoderm (PSM) and somites at 9.5 dpc. Expressed in endothelial and smooth muscle cells of blood vessels at 9.5 dpc (PubMed:11562355). Expressed in growth plate chondrocytes and perichondrial cells at 13.5 dpc (at protein level) (PubMed:25808752). Expressed in non-notochordal mesoderm surrounding the node and notochord at 7.5 dpc (PubMed:9106663). Expressed in anterior presomitic mesoderm adjacent to somites, in the somites, and in the cephalic mesoderm at 8.5 and 9.5 dpc (PubMed:9106663). Detected weakly in yolk sac at 9.5 dpc (PubMed:11562355). Expressed in presumptive intermediate mesoderm, as well as in the presomitic mesoderm and somites at 8.5 and 9.5 dpc (PubMed:10704385). Expressed in the metanephric mesenchyme of the kidney at 10.5 and 12.5 dpc (PubMed:10704385). Expressed during the developing cardiovascular system (PubMed:10479458). Expressed in the branchial arches and mesenchymal cells surrounding the eye at 10.5 dpc (PubMed:9106663). Expressed in nasal processes, corneal mesenchyme cells, branchial arches, blood vessels and endocardium at 11.5 dpc (PubMed:9106663, PubMed:10395790). Expressed in cells located in the presumptive anterior segment that are fated to contribute to the corneal endothelium or stroma, as well as within cells located at the periphery of the optic cup at 11.5 dpc (PubMed:16449236). Expressed in periocular mesenchyme cells at 11.5, 12.5 and 16.5 dpc (PubMed:10395790, PubMed:16449236). Expressed in developing limb buds at 12.5 dpc (PubMed:25808752). Expressed in chondrocytes at 15 dpc (PubMed:25808752). Expressed in the trabecular meshwork cells, the sclera, the conjunctival epithelium and the corneal epithelium at 16.5 dpc (PubMed:10395790). Strongly expressed in adipo-osteogenic progenitor cells (CXCL12-abundant reticular (CAR) cells) at 16.5 dpc and at birth (PubMed:24590069).|||Monomer. Interacts with C1QBP (By similarity). Interacts (via N-terminus) with GLI2 (via C-terminal internal region); this interaction is direct and increases GLI2 DNA-binding and transcriptional activity through a smoothened (SMO)-independent Hedgehog (Hh) signaling pathway (PubMed:26565916, PubMed:25808752). Interacts (via C-terminus domain) with PITX2 (via homeobox domain) (By similarity). Interacts with FLNA and PBX1 (By similarity).|||Nucleus|||Phosphorylated (PubMed:22493429). Phosphorylated on Ser-274 in response to epidermal growth factor (EGF) in a ERK1/2 MAPK-dependent signaling pathway; phosphorylation contributes to its protein stability and transcriptional regulatory activity (By similarity).|||Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP2.|||Ubiquitinated, leading to its proteasomal degradation. http://togogenome.org/gene/10090:Or2y1b ^@ http://purl.uniprot.org/uniprot/Q60883 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Rpl37rt ^@ http://purl.uniprot.org/uniprot/Q9D823 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL37 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Ccdc78 ^@ http://purl.uniprot.org/uniprot/D3Z5T1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CCDC78 family.|||Component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells that can generate more than 100 centrioles. Deuterosome-mediated centriole amplification occurs in terminally differentiated multiciliated cells (G1/0) and not in S phase. Essential for centriole amplification and is required for CEP152 localization to the deuterosome (By similarity).|||Sarcoplasmic reticulum|||centriole|||perinuclear region|||sarcolemma http://togogenome.org/gene/10090:Nr1h3 ^@ http://purl.uniprot.org/uniprot/Q91X41|||http://purl.uniprot.org/uniprot/Q9Z0Y9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Cytoplasm|||Heterodimer of NR1H3 and RXR (retinoic acid receptor). Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with SIRT1 and this interaction is inhibited by CCAR2 (By similarity).|||Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:18055760, PubMed:19520913, PubMed:20427281). Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (PubMed:28846071, PubMed:25806685). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (PubMed:25806685). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (PubMed:24206663).|||Nucleus|||Ubiquitinated leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Or52e19 ^@ http://purl.uniprot.org/uniprot/F8VQ26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Polb ^@ http://purl.uniprot.org/uniprot/Q8K409 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-X family.|||Binds 2 magnesium ions per subunit.|||Cytoplasm|||Methylation by PRMT6 stimulates the polymerase activity by enhancing DNA binding and processivity.|||Monomer (By similarity). Binds single-stranded DNA (ssDNA) (By similarity). Interacts with APEX1, LIG1, LIG3, FEN1, PCNA and XRCC1 (By similarity). Interacts with HUWE1/ARF-BP1, STUB1/CHIP and USP47 (By similarity). Interacts with FAM168A (By similarity).|||Nucleus|||Repair polymerase that plays a key role in base-excision repair. During this process, the damaged base is excised by specific DNA glycosylases, the DNA backbone is nicked at the abasic site by an apurinic/apyrimidic (AP) endonuclease, and POLB removes 5'-deoxyribose-phosphate from the preincised AP site acting as a 5'-deoxyribose-phosphate lyase (5'-dRP lyase); through its DNA polymerase activity, it adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases. It is also able to cleave sugar-phosphate bonds 3' to an intact AP site, acting as an AP lyase.|||Residues 239-252 form a flexible loop which appears to affect the polymerase fidelity.|||Ubiquitinated at Lys-41, Lys-61 and Lys-81: monoubiquitinated by HUWE1/ARF-BP1. Monoubiquitinated protein is then the target of STUB1/CHIP, which catalyzes polyubiquitination from monoubiquitin, leading to degradation by the proteasome. USP47 mediates the deubiquitination of monoubiquitinated protein, preventing polyubiquitination by STUB1/CHIP and its subsequent degradation (By similarity). http://togogenome.org/gene/10090:Trafd1 ^@ http://purl.uniprot.org/uniprot/Q3UDK1 ^@ Disruption Phenotype|||Function|||Induction|||Subunit|||Tissue Specificity ^@ By lipopolysaccharide (LPS), IFNB1 and IFNG, IFNB1 being most rapid and potent inducer (at protein level). Not induced by anti-inflammatory cytokines, such as IL4 and IL10, which also inhibit LPS induction of TRAFD1.|||Expressed in skeletal muscle, brain, liver, kidney, spleen and bone marrow. Expression depends on STAT1.|||Interacts with MAVS, TICAM1, TRAF1, TRAF2, TRAF3 and TRAF6.|||Mice show no gross developmental abnormalities, but exhibit an increased susceptibility to LPS-induced septic shock and are more sensitive to poly(I:C) shock, suffering more severe hepatic damage than wild-type animals. In response to LPS-stimulation, bone marrow-derived dendritic cells display an increased production of pro-inflammatory cytokines, such as IL6, TNF and IL12, as well as elevated IKK and JNK activation, compared to wild-type mice. Mutant embryonic fibroblasts are more resistant to vesicular stomatitis virus (VSV)-induced cytopathic effect.|||Negative feedback regulator that controls excessive innate immune responses. Regulates both Toll-like receptor 4 (TLR4) and DDX58/RIG1-like helicases (RLH) pathways. May inhibit the LTR pathway by direct interaction with TRAF6 and attenuation of NF-kappa-B activation. May negatively regulate the RLH pathway downstream from MAVS and upstream of NF-kappa-B and IRF3. http://togogenome.org/gene/10090:Zfp202 ^@ http://purl.uniprot.org/uniprot/Q8C879 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Mtf1 ^@ http://purl.uniprot.org/uniprot/Q07243 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Nucleus|||Ubiquitously expressed.|||Zinc-dependent transcriptional regulator of cellular adaption to conditions of exposure to heavy metals (PubMed:24529376). Binds to metal responsive elements (MRE) in promoters and activates the transcription of metallothionein genes like metallothionein-2/MT2A (By similarity). Also regulates the expression of metalloproteases in response to intracellular zinc and functions as a catabolic regulator of cartilages (PubMed:24529376). http://togogenome.org/gene/10090:Rtca ^@ http://purl.uniprot.org/uniprot/Q9D7H3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RNA 3'-terminal cyclase family. Type 1 subfamily.|||Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA (By similarity). The mechanism of action of the enzyme occurs in 3 steps: (A) adenylation of the enzyme by ATP; (B) transfer of adenylate to an RNA-N3'P to produce RNA-N3'PP5'A; (C) and attack of the adjacent 2'-hydroxyl on the 3'-phosphorus in the diester linkage to produce the cyclic end product (By similarity). Likely functions in some aspects of cellular RNA processing (PubMed:25961792). Function plays an important role in regulating axon regeneration by inhibiting central nervous system (CNS) axon regeneration following optic nerve injury (PubMed:25961792).|||Detected in retinal ganglion cells (RGCs) (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Tulp2 ^@ http://purl.uniprot.org/uniprot/A0A1B0GRN6|||http://purl.uniprot.org/uniprot/D3Z0R4|||http://purl.uniprot.org/uniprot/P46686 ^@ Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TUB family.|||Cytoplasm|||Expressed in retina and testis.|||Secreted|||Was originally thought to be a phosphodiesterase on the basis of spurious sequence similarities. http://togogenome.org/gene/10090:Grk5 ^@ http://purl.uniprot.org/uniprot/Q3TST4|||http://purl.uniprot.org/uniprot/Q8VEB1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.|||Cell membrane|||Cytoplasm|||Inhibited by calmodulin with an IC(50) of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid (By similarity).|||Interacts with ST13 (via the C-terminus 303-319 AA) (By similarity). Interacts with TP53/p53 (By similarity). Interacts with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT (serotonin) (PubMed:18711143). Interacts with HDAC5 (By similarity). Interacts with GIT1 (By similarity).|||No obvious phenotype due to the redundancy of GRK subtypes in the regulation of GPCR signaling. Deficient mice are viable and showed no anatomic or behavioral abnormalities, only a slight decrease in body temperature. However deficient mice shown altered central and lung M2 muscarinic receptor regulation, with normal heart M2 receptor regulation. GRK5 deficiency leads to a reduced hippocampal acetylcholine release and cholinergic hypofunction by selective impairment of desensitization of presynaptic M2/M4 autoreceptors and promotes amyloid-beta accumulation.|||Nucleus|||Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro). http://togogenome.org/gene/10090:Slc16a6 ^@ http://purl.uniprot.org/uniprot/B1AT66 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Forms functional complexes with BSG/CD147 or EMB/GP70 ancillary proteins.|||Monocarboxylate transporter selective for taurine. May associate with BSG/CD147 or EMB/GP70 ancillary proteins to mediate facilitative efflux or influx of taurine across the plasma membrane. The transport is pH- and sodium-independent. Rather low-affinity, is likely effective for taurine transport in tissues where taurine is present at high concentrations. http://togogenome.org/gene/10090:Cep89 ^@ http://purl.uniprot.org/uniprot/Q9CZX2 ^@ Function|||Subcellular Location Annotation ^@ Mitochondrion intermembrane space|||Required for ciliogenesis. Also plays a role in mitochondrial metabolism where it may modulate complex IV activity (By similarity).|||centriole|||centrosome|||cytosol|||spindle pole http://togogenome.org/gene/10090:Qrich1 ^@ http://purl.uniprot.org/uniprot/Q3UA37 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed highly in prefrontal cortex, craniofacial area and near the limbs of mouse embryos. Expressed in heart, skeletal muscle, liver, kidney, lung, brain, spleen, intestine and growth plate in mice.|||Nucleus|||The CARD domain may be involved in the regulation of caspase activity in the context of programmed cell death.|||Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress (PubMed:33384352). Controls the outcome of the unfolded protein response (UPR), an ER-stress response pathway that either promotes recovery of ER homeostasis and cell survival, or triggers the terminal UPR which elicits programmed cell death when ER stress is prolonged and unresolved (PubMed:33384352). ER stress induces QRICH1 translation by a ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced QRICH1 regulates a transcriptional program associated with protein translation, protein secretion-mediated proteotoxicity and cell death during the terminal UPR (By similarity). May cooperate with ATF4 transcription factor signaling to regulate ER homeostasis which is critical for cell viability (By similarity). Up-regulates CASP3/caspase-3 activity in epithelial cells under ER stress. Central regulator of proteotoxicity associated with ER stress-mediated inflammatory diseases in the intestines and liver (PubMed:33384352). Involved in chondrocyte hypertrophy, a process required for normal longitudinal bone growth (PubMed:30281152). http://togogenome.org/gene/10090:Pagr1a ^@ http://purl.uniprot.org/uniprot/Q99L02 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the KMT2 family MLL2/MLL3 complex, at least composed of the histone methyltransferases KMT2D and/or KMT2C, the common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; PAXIP1 is required for the association with the MLL2/MLL3 complex (By similarity). Forms a constitutive complex with PAXIP1/PTIP independently of the MLL2/MLL3 complex (PubMed:19124460, PubMed:26744420). Interacts with NCOA1, ESR1, NR3C1, AR (By similarity).|||Expression first detected at 5.0-6.0 dpc in the extraembryonic region, at 7.5 dpc detected within the chorion; later the expression is expanding to the entire embryo.|||Its association with the histone methyltransferase MLL2/MLL3 complex is suggesting a role in epigenetic transcriptional activation. However, in association with PAXIP1/PTIP is proposed to function at least in part independently of the MLL2/MLL3 complex. Proposed to be recruited by PAXIP1 to sites of DNA damage where the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage independently of the MLL2/MLL3 complex (PubMed:19124460). However, its function in DNA damage has been questioned (PubMed:26744420). During immunoglobulin class switching in activated B-cells is involved in transcription regulation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus independently of the MLL2/MLL3 complex (PubMed:26744420). Involved in both estrogen receptor-regulated gene transcription and estrogen-stimulated G1/S cell-cycle transition (By similarity). Acts as transcriptional cofactor for nuclear hormone receptors. Inhibits the induction properties of several steroid receptors such as NR3C1, AR and PPARG; the mechanism of inhibition appears to be gene-dependent (By similarity). May be involved in the regulation of the BMP pathway in extraembryonic development (PubMed:24633704).|||Normal germ layer specification and developmental patterning but limited anterior development and arrest by 8.5 dpc, likely due at least in part to defects in extraembryonic tissue.|||Nucleus|||The terminology of MLL proteins in mammalia is not consistent also concerning the terminology of MLL protein-containing complexes. The decribed MLL2/MLL3 complex is commonly described as MLL3/MLL4 complex in literature. http://togogenome.org/gene/10090:Ntn3 ^@ http://purl.uniprot.org/uniprot/Q9R1A3 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Netrins control guidance of CNS commissural axons and peripheral motor axons.|||Very low levels at 10.5 to 12.5 dpc in dorsal root ganglia. High levels in motor neurons at 13.5, 14.5 and 15.5 dpc. At 11.5 dpc also expressed in the developing limb buds.|||extracellular matrix http://togogenome.org/gene/10090:Rsad1 ^@ http://purl.uniprot.org/uniprot/Q5SUV1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the anaerobic coproporphyrinogen-III oxidase family. HemW subfamily.|||May be a heme chaperone, appears to bind heme. Homologous bacterial proteins do not have oxygen-independent coproporphyrinogen-III oxidase activity (By similarity). Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine (By similarity).|||Might carry two S-adenosyl-L-methionine binding sites with only one binding to the iron-sulfur cluster.|||Mitochondrion http://togogenome.org/gene/10090:Nde1 ^@ http://purl.uniprot.org/uniprot/Q9CZA6 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nudE family.|||Cleavage furrow|||Highly expressed in ovary. Also expressed in brain, heart, kidney, large intestine, liver, lung, small intestine and testis.|||Homozygous loss of this protein results in microcephaly that preferentially affects the cerebral cortex. Affected animals have a smaller cortex with reduced superficial cortical layers, although cortical lamination is mostly preserved. The smaller cortex size seems to reflect both reduced progenitor cell division and altered specification of cell fates following progenitor cell division.|||Interacts with dynactin and PCM1 (By similarity). Self-associates. Interacts with CENPF, LIS1, CNTRL, dynein, tubulin gamma, PAFAH1B1, PCNT, SLMAP and TCP1. Interacts with ZNF365 (By similarity).|||Phosphorylated in mitosis (By similarity). Phosphorylation at Thr-246 is essential for the G2/M transition.|||Required for centrosome duplication and formation and function of the mitotic spindle. Essential for the development of the cerebral cortex. May regulate the production of neurons by controlling the orientation of the mitotic spindle during division of cortical neuronal progenitors of the proliferative ventricular zone of the brain. Orientation of the division plane perpendicular to the layers of the cortex gives rise to two proliferative neuronal progenitors whereas parallel orientation of the division plane yields one proliferative neuronal progenitor and a post-mitotic neuron. A premature shift towards a neuronal fate within the progenitor population may result in an overall reduction in the final number of neurons and an increase in the number of neurons in the deeper layers of the cortex.|||Widely expressed in the developing brain, particularly in the neural progenitor cells of ventricular zone and the intermediate zone of the cerebral cortex. Expression peaks at 11 dpc and declines at 15 dpc and 17 dpc. After completion of neuronal migration expression is reduced in the cortex.|||centrosome|||cytoskeleton|||kinetochore|||spindle http://togogenome.org/gene/10090:Ifih1 ^@ http://purl.uniprot.org/uniprot/D2CGM4|||http://purl.uniprot.org/uniprot/Q8R5F7 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the helicase family. RLR subfamily.|||By interferon (IFN).|||Cytoplasm|||During apoptosis, processed into 3 cleavage products. The helicase-containing fragment, once liberated from the CARD domains, translocate from the cytoplasm to the nucleus. The processed protein significantly sensitizes cells to DNA degradation.|||Expression is prominent in lung, liver, kidney, heart and spleen (at protein level). Widely expressed at low level.|||ISGylated by ISG15. ISGylation increases upon infection with viruses. ISGylation at Lys-23 and Lys-43 is dependent of dephosphorylation, regulates mitochondrial translocation and oligomerization. Essential for IFIH1/MDA5-mediated cytokine responses and restriction of virus replication.|||Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines. Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and theiler's murine encephalomyelitis virus (TMEV). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.|||Mitochondrion|||Monomer in the absence of ligands and homodimerizes in the presence of dsRNA ligands. Can assemble into helical or linear polymeric filaments on long dsRNA. Interacts with MAVS/IPS1. Interacts (via the CARD domains) with TKFC, the interaction is inhibited by viral infection. Interacts with PCBP2. Interacts with NLRC5. Interacts with PIAS2-beta. Interacts with DDX60. Interacts with ANKRD17. Interacts with IKBKE. Interacts with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates. Interacts with ZCCHC3; leading to activate IFIH1/MDA5. Interacts with RNF123. Interacts with DDX3X. Interacts with NOD1; this interaction promotes transcription of antiviral genes and inhibition of viral replication. Interacts with ECSIT; this interaction bridges IFIH1 to the MAVS complex at the mitochondrion.|||Nucleus|||Phosphorylated. Dephosphorylated by phsophatases PP1; dephosphorylation precedes and is required for ISGylation.|||Sumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta.|||Ubiquitinated by RNF125, leading to its degradation by the proteasome. USP17/UPS17L2-dependent deubiquitination positively regulates the receptor. Ubiquitinated by TRIM25 via 'Lys-63'-linked ubiquitination, promoting activation of IFIH1/MDA5. Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal degradation. Ubiquitinated by TRIM65 via 'Lys-63'-linked ubiquitination, promoting activation of IFIH1/MDA5. http://togogenome.org/gene/10090:4921507P07Rik ^@ http://purl.uniprot.org/uniprot/Q9D5Y0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme. May serve to reinforce and thus stabilize the microtubule structure in the sperm flagella.|||Predominantly expressed in the testes.|||The testis size, weight and histology, spermatogenesis, and sperm morphology and motility are normal in homozygous knockout males.|||centrosome|||flagellum axoneme http://togogenome.org/gene/10090:Clic5 ^@ http://purl.uniprot.org/uniprot/A0A668KLB7|||http://purl.uniprot.org/uniprot/Q8BXK9 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the chloride channel CLIC family.|||Component of a multimeric complex consisting of several cytoskeletal proteins, including actin, ezrin, alpha-actinin, gelsolin, and IQGAP1. Interacts with AKAP9 (By similarity).|||Cytoplasm|||Defects in Clic5 are a cause of the jitterbug (jbg) phenotype. Jbg is the result of a spontaneous mutation that leads to severe degeneration of the organ of Corti in the inner ear. Jbg leads to progressive degeneration of inner ear hair cells. Affected mice are identified by head bobbing, circling behavior and their inability to swim. They cannot hear well when young, and become completely deaf after 5 months (PubMed:17021174). In addition, there are eye defects with aberrant development of the lens suture and formation of lens opacities (PubMed:29425878).|||Detected in lung and inner ear. Detected in embryonic cochlea, on microvilli-covered apical surfaces of interdental cells, columnar cells of Kolliker's organ, and on stereocilia of inner and outer hair cells (at protein level) (PubMed:17021174). Also detected in the eye, where it localizes to lens fiber cells in the lens epithelium (at protein level) (PubMed:29425878).|||Golgi apparatus|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity).|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.|||Membrane|||Mitochondrion|||Required for normal hearing (By similarity). It is necessary for the formation of stereocilia in the inner ear and normal development of the organ of Corti. Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. May play a role in the regulation of transepithelial ion absorption and secretion. Is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture (PubMed:17021174). Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens (PubMed:29425878).|||cell cortex|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Nkx1-2 ^@ http://purl.uniprot.org/uniprot/P42580 ^@ Developmental Stage|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aberrant splicing.|||Belongs to the NK-1 homeobox family.|||Expression detected in adult brain, testis and spleen. In the testis, expressed in the germ cells of the seminiferous epithelium, in elongating spermatids and in spermatozoa. Expressed throughout the brain with highest levels in regions of the cerebral cortex, hippocampus, diencephalon, pons, medulla and cerebellum. In the embryo, expressed in the developing posterior central nervous system. First seen in the ectoderm lateral to the primitive streak, later it encompasses the neural plate. Starting at day 9.5 pc, expressed in distinct areas of spinal cord, hindbrain, midbrain and forebrain.|||In the embryo, expressed at highest levels at day 10 with levels decreasing during further development.|||Interacts with HIPK1, HIPK2, and HIPK3.|||May function in cell specification, particularly in the CNS.|||Nucleus|||Phosphorylated by HIPK2 in vitro.|||Probable cloning artifact. http://togogenome.org/gene/10090:Pparg ^@ http://purl.uniprot.org/uniprot/M1VPI1|||http://purl.uniprot.org/uniprot/P37238|||http://purl.uniprot.org/uniprot/Q6GU14 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Cytoplasm|||Expressed in a circadian manner in the aorta.|||Heterodimer with other nuclear receptors, such as RXRA. The heterodimer with the retinoic acid receptor RXRA is called adipocyte-specific transcription factor ARF6. Interacts with NCOA6 coactivator, leading to a strong increase in transcription of target genes. Interacts with coactivator PPARBP, leading to a mild increase in transcription of target genes. Interacts with NOCA7 in a ligand-inducible manner. Interacts with NCOA1 and NCOA2 LXXLL motifs. Interacts with ASXL1, ASXL2, DNTTIP2, FAM120B, MAP2K1/MEK1, NR0B2, PDPK1, PRDM16, PRMT2 and TGFB1I1. Interacts (when activated by agonist) with PPP5C. Interacts with HELZ2 and THRAP3; the interaction stimulates the transcriptional activity of PPARG. Interacts with PER2, the interaction is ligand dependent and blocks PPARG recruitment to target promoters. Interacts with NOCT. Interacts with FOXO1 (acetylated form). Interacts with ACTN4 (By similarity). Interacts (when in the liganded conformation) with GPS2 (PubMed:25519902). Interacts with CRY1 and CRY2 in a ligand-dependent manner (PubMed:28683290). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).|||Heterodimer with other nuclear receptors.|||Highest expression in white and brown adipose tissue. Also found in liver, skeletal muscle, heart, adrenal gland, spleen, kidney and intestine. Isoform 2 is more abundant than isoform 1 in adipose tissue.|||It appears first at 13.5 dpc and increases until birth.|||Mice develop abnormalities in circadian variations in blood pressure and heart rate, in parallel with a reduction of diurnal variations in the sympathetic nerve activity, and impaired rhythmicity of BMAL1 in the blood vessels.|||Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (PubMed:19041764).|||Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. May play a role in the regulation of circadian rhythm.|||Nucleus|||O-GlcNAcylation at Thr-84 reduces transcriptional activity in adipocytes.|||PDPK1 activates its transcriptional activity independently of its kinase activity.|||Phosphorylated in basal conditions and dephosphorylated when treated with the ligand. May be dephosphorylated by PPP5C. The phosphorylated Ser-112 form is recognized by PER2 and repressed, dephosphorylation at Ser-112 induces adipogenic activity. Ser-112 phosphorylation levels are reduced by 65% in brown adipose tissue compared to white adipose tissue.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO9; leading to proteasomal degradation. http://togogenome.org/gene/10090:Rerg ^@ http://purl.uniprot.org/uniprot/Q8R367 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Ras family.|||Binds GDP/GTP and possesses intrinsic GTPase activity. Has higher affinity for GDP than for GTP (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:4930590J08Rik ^@ http://purl.uniprot.org/uniprot/Q8CDN1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Il22b ^@ http://purl.uniprot.org/uniprot/Q9JJY8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-10 family.|||Cytokine that contributes to the inflammatory response in vivo.|||Secreted http://togogenome.org/gene/10090:Rgs7 ^@ http://purl.uniprot.org/uniprot/O54829 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Detected in brain (at protein level).|||GTPase activator component of the RGS7-GNB5 complex that regulates G protein-coupled receptor signaling cascades (PubMed:25792749). The RGS7-GNB5 complex acts as an inhibitor signal transduction by promoting the GTPase activity of G protein alpha subunits, such as GNAO1, thereby driving them into their inactive GDP-bound form (By similarity). May play a role in synaptic vesicle exocytosis (By similarity). Glycine-dependent regulation of the RGS7-GNB5 complex by GPR158 affects mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (PubMed:31311860, PubMed:30546127). Modulates the activity of potassium channels that are activated by GNAO1 in response to muscarinic acetylcholine receptor M2/CHRM2 signaling (By similarity).|||Interacts with GNB5, forming the RGS7-GNB5 complex (By similarity). Interacts with GPR158; promotes the GTPase activator activity of the RGS7-GNB5 complex in absence of glycine, in contrast GTPase activator activity of the RGS7-GNB5 complex is inhibited in presence of glycine (PubMed:22689652, PubMed:25792749, PubMed:31311860). Interacts with GPR179 (PubMed:22689652). Interacts with PKD1; this prevents rapid proteasomal degradation (By similarity). Interacts with RGS7BP, leading to regulate the subcellular location of the heterodimer formed with GNB5 (PubMed:15632198, PubMed:15897264). Interacts (phosphorylated form) with 14-3-3 protein YWHAQ (PubMed:10862767). Interacts with SNAPIN (By similarity). Interacts with GNAI1 (By similarity). Interacts with GNAO1, GNAI3 and GNAZ (By similarity).|||Membrane|||Palmitoylated.|||Phosphorylation and subsequent interaction with 14-3-3 proteins inhibits GAP activity.|||Ubiquitinated, leading to rapid proteasomal degradation.|||cytosol http://togogenome.org/gene/10090:Hsd17b6 ^@ http://purl.uniprot.org/uniprot/Q9R092 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Detected in liver.|||Early endosome membrane|||Inhibited by carbenoxolone and phenyl arsenoxide.|||Microsome membrane|||NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). http://togogenome.org/gene/10090:Clcn6 ^@ http://purl.uniprot.org/uniprot/O35454|||http://purl.uniprot.org/uniprot/Q3UM91 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family.|||Belongs to the chloride channel (TC 2.A.49) family. ClC-6/CLCN6 subfamily.|||Detected in whole brain and in hippocampus neurons (at protein level). Detected in brain, trigeminus, dorsal root ganglion, spinal cord, eye, kidney, testis, skeletal muscle, thymus and pancreas. Isoform ClC-6c is expressed only in kidney.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Late endosome membrane|||Membrane|||N-glycosylated on several asparagine residues.|||Reduced pain sensitivity and moderate behavioral abnormalities, but have normal fertility and are generally not very different from wild-type.|||Voltage-gated channel mediating the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the late endosome lumen. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The presence of conserved gating glutamate residues is typical for family members that function as antiporters. http://togogenome.org/gene/10090:Cdnf ^@ http://purl.uniprot.org/uniprot/Q8CC36 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At postnatal stage P1 and P10, expressed in the brain, including the hippocampus, thalamus, striatum and substantia nigra. Highest levels in the hippocampus and thalamus.|||Belongs to the ARMET family.|||Expressed at high levels in the heart, skeletal muscle, testis and brain (at protein level). In the brain, detected in the cerebral cortex neurons through layers II to VI. In the hippocampus, detected in the CA1 to CA3 pyramidal regions and in the granule and polymorph layers of dentate gyrus. Weak expression in the striatum. In substantia nigra, detected in solitary cells that did not express tyrosine hydroxylase, a marker for dopaminergic neurons. Relatively high expression in the Purkinje cells of the cerebellum and in regions of the brain stem, including the locus coeruleus.|||Secreted|||Trophic factor for dopamine neurons. Prevents the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When administered after 6-OHDA-lesioning, restores the dopaminergic function and prevents the degeneration of dopaminergic neurons in substantia nigra (By similarity). http://togogenome.org/gene/10090:H3c2 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Lor ^@ http://purl.uniprot.org/uniprot/P18165 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Tissue Specificity ^@ Contains inter- or intramolecular disulfide-bonds.|||Expressed in the epidermis of the ear (at protein level).|||Expressed in the spinous and granular layers of the tongue at P20.|||Major keratinocyte cell envelope protein.|||Substrate of transglutaminases. Some glutamines and lysines are cross-linked to other loricrin molecules and to SPRRs proteins.|||Transgenic mice expressing a C-terminal truncated form of loricrin exhibited, at birth, erythrokeratoderma with an epidermal barrier dysfunction. 4 days after birth, high-expressing transgenic animals showed a generalized scaling of the skin, as well as a constricting band encircling the tail and, by day 7, a thickening of the footpads. Transgenic mice also showed retention of nuclei in the stratum corneum. The mutant loricrin protein is found in the nucleus and cytoplasm of epidermal keratinocytes, but is not detect in the cornified cell envelope. The C-terminal domain of the mutant loricrin contains a nuclear localization signal. http://togogenome.org/gene/10090:Fbxl13 ^@ http://purl.uniprot.org/uniprot/Q8CDU4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DRC6 family.|||Component of the nexin-dynein regulatory complex (N-DRC). Directly interacts with SKP1 and CUL1 (By similarity). Interacts with TCTE1/DRC5 (PubMed:28630322).|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Specifically targets CEP192 isoform 3 for ubiquitin-mediated proteolysis and thereby acts as a regulator of microtubule nucleation activity.|||centrosome|||flagellum axoneme http://togogenome.org/gene/10090:Krt33b ^@ http://purl.uniprot.org/uniprot/Q61897 ^@ Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed strongly in cortex cells in newborn back skin and in the central unit of the lingual filiform papillae.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Gngt1 ^@ http://purl.uniprot.org/uniprot/Q61012 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||Retinal rod outer segment. http://togogenome.org/gene/10090:Fank1 ^@ http://purl.uniprot.org/uniprot/Q9DAM9 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expression is activated by FOXJ1.|||In the developing testis, first detected at postnatal day 14 (P14) and levels increase after P20 (at protein level). At P20, detected in pachytene spermatocytes and round spermatids, but not in preleptotene and leptotene spermatocytes. Not detected in testis at P10. Detected in germinal vesicle (GV) stage oocytes and in embryos up to the 2-cell stage, but not in morula or blastocysts.|||Interacts with COPS5; regulates the phosphorylation of JUN and the transcriptional activity of AP-1. Interacts with RYBP; may prevent the ubiquitin-mediated proteasomal degradation of FANK1.|||Mostly restricted to testis (at protein level), including mid to late pachytene spermatocytes (stages VI-X), diplotene spermatocytes (stage XI), meiotically dividing spermatocytes (stage XII) and spermatids in steps 1-14. Highest levels in late pachytene spermatocytes and spermatids in steps 1-9.|||Nucleus|||Polyubiquitinated. Polyubiquitination leads to proteasomal degradation.|||The fibronectin type-III domain mediates interaction with COPS5 and RYBP.|||Through the activation of JUN and AP-1-mediated transcription, may regulate apoptosis.|||cilium|||cilium basal body|||cytosol http://togogenome.org/gene/10090:Or5t17 ^@ http://purl.uniprot.org/uniprot/Q8VES2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Or1j19 ^@ http://purl.uniprot.org/uniprot/Q8VGK3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mfn1 ^@ http://purl.uniprot.org/uniprot/Q811U4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A helix bundle is formed by helices from the N-terminal and the C-terminal part of the protein. The GTPase domain cannot be expressed by itself, without the helix bundle. Rearrangement of the helix bundle and/or of the coiled coil domains may bring membranes from adjacent mitochondria into close contact, and thereby play a role in mitochondrial fusion.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. Mitofusin subfamily.|||Detected in adult heart (PubMed:12759376). Detected in embryos (at protein level) (PubMed:12527753). Widely expressed (PubMed:11950885).|||Expressed in 8.5 dpc, 9.5 dpc, 10.5 dpc and 11.5 dpc embryos.|||Full embryonic lethality; nearly 90% of the mutant embryos have been resorbed at 11.5 dpc (PubMed:12527753). Contrary to wild-type embryonic fibroblasts that have elongated, tubular mitochondria, mutant embryonic fibroblasts contain only fragmented mitochondria (PubMed:12527753). In cultured cells, mutant mitochondria show a strongly decreased frequency of mitochondrial fusion events (PubMed:12527753). In spite of the aberrant mitochondrial morphology, there seem to be no gross defects in respiration (PubMed:12527753). Heart-specific disruption of Mfn1 does not impair heart function and has no effect on cardiomyocyte mitochondrial morphometry or respiratory function (PubMed:23620051).|||Homodimer, also in the absence of bound GTP (By similarity). Forms higher oligomers in the presence of a transition state GTP analog (By similarity). Forms homomultimers and heteromultimers with MFN2 (PubMed:12527753). Oligomerization is essential for mitochondrion fusion (PubMed:15297672). Component of a high molecular weight multiprotein complex (By similarity). Interacts with VAT1 (By similarity). Interacts with THG1L; THG1L probably functions as a guanyl-nucleotide exchange factor/GEF, activating MFN1.|||Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:12527753, PubMed:23921378, PubMed:24513856, PubMed:15297672). Membrane clustering requires GTPase activity (By similarity). It may involve a major rearrangement of the coiled coil domains (PubMed:15297672). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:12527753). Overexpression induces the formation of mitochondrial networks (in vitro). Has low GTPase activity (By similarity).|||Mitochondrion outer membrane|||Ubiquitinated by MARCHF5 (By similarity). When mitochondria are depolarized and dysfunctional, it is ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that contains FBXO7 and PRKN. Ubiquitinated by non-degradative ubiquitin by PRKN, promoting mitochondrial fusion; deubiquitination by USP30 inhibits mitochondrial fusion (PubMed:24513856). http://togogenome.org/gene/10090:Ddah1 ^@ http://purl.uniprot.org/uniprot/D3YU15|||http://purl.uniprot.org/uniprot/Q3UF01|||http://purl.uniprot.org/uniprot/Q9CWS0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the DDAH family.|||Death at embryonic stages. Heterozygous mice show no visible phenotype, but have higher than normal tissue and plasma levels of asymmetric dimethylarginine (ADMA). They have increased mean arterial blood pressure and systemic vascular resistance, and decreased cardiac output and heart rate, probably due to reduced levels of nitric oxide (NO).|||Detected in skeletal muscle, lung, heart and brain (at protein level). Detected in liver, kidney and lung.|||Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.|||Inhibited by zinc ions.|||Monomer. http://togogenome.org/gene/10090:Ganab ^@ http://purl.uniprot.org/uniprot/A1A4T2|||http://purl.uniprot.org/uniprot/Q8BHN3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 31 family.|||Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:27462106). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:28375157).|||Endoplasmic reticulum|||Golgi apparatus|||Heterodimer of a catalytic alpha subunit (GANAB) and a beta subunit (PRKCSH) (PubMed:9148925, PubMed:10921916, PubMed:27462106). Binds glycosylated PTPRC (PubMed:9148925, PubMed:10921916).|||May be due to an intron retention.|||Melanosome http://togogenome.org/gene/10090:Vmn2r34 ^@ http://purl.uniprot.org/uniprot/E9PVI0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Negr1 ^@ http://purl.uniprot.org/uniprot/Q80Z24 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. IgLON family.|||Cell membrane|||Expressed in brain.|||May be involved in cell-adhesion. May function as a trans-neural growth-promoting factor in regenerative axon sprouting in the mammalian brain. http://togogenome.org/gene/10090:Hnrnpr ^@ http://purl.uniprot.org/uniprot/F7B5B5|||http://purl.uniprot.org/uniprot/Q3U8W9|||http://purl.uniprot.org/uniprot/Q3UKV5|||http://purl.uniprot.org/uniprot/Q3UZI0|||http://purl.uniprot.org/uniprot/Q8VHM5 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Ctsk ^@ http://purl.uniprot.org/uniprot/P55097|||http://purl.uniprot.org/uniprot/Q545T0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the peptidase C1 family.|||Enlarged thyroid follicles, reduced extension of the thyroid epithelium, and slight increase in the levels of Tg/thyroglobulin in the thyroid follicles. Loss of localization of CTSB/cathepsin B and L to the apical membrane of thyroid epithelial cells. Serum levels of thyroid hormone thyroxine (T4) are normal. However, reduction in T4 levels is more severe in CTSK and CTSL double knockout mice compared to CTSL double knockout mice.|||Expressed in new born and adults.|||Lysosome|||Predominantly expressed in bones (PubMed:8814310). Expressed in thyroid epithelial cells (PubMed:12782676).|||Secreted|||Thiol protease involved in osteoclastic bone resorption. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation (By similarity). Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:12782676). http://togogenome.org/gene/10090:Smyd1 ^@ http://purl.uniprot.org/uniprot/P97443 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Cytoplasm|||Expressed in cardiac and skeletal muscle, lymphocytes and thymus.|||Interacts with HDAC1, HDAC2 and HDAC3. Interacts (via MYND-type zinc finger) with NACA isoform skNAC.|||Methylates histone H3 at 'Lys-4' (H3K4me). Acts as a transcriptional repressor. Essential for cardiomyocyte differentiation and cardiac morphogenesis.|||Nucleus|||The SET domain is split between the S-sequence (residues 1-49) and the core SET domain (residues 181-258), however the two segments still come together to form a conserved SET domain fold. http://togogenome.org/gene/10090:Chst2 ^@ http://purl.uniprot.org/uniprot/Q80WV3 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.|||Homodimer; disulfide-linked. Homodimerization is not essential for enzyme activity (By similarity).|||In brain, it is expressed in pyramidal cells in the CA3 subregion of the hippocampus, cerebellar nucleus and Purkinje cells. Expressed in peripheral lymph nodes.|||It is uncertain whether Met-1 or Met-48 is the initiator.|||Mice are impaired in the elaboration of sialyl 6-sulfo Lewis X in HEV. Lymphocyte homing to peripheral lymph nodes, mesenteric lymph nodes, and Peyer patches are significantly reduced. Simultaneous knockdown of CHST4 and CHST2 results in lower contact hypersensitivity response when compared to wild-type littermates.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues within keratan-like structures on N-linked glycans and within mucin-associated glycans that can ultimately serve as SELL ligands. SELL ligands are present in high endothelial cells (HEVs) and play a central role in lymphocyte homing at sites of inflammation. Participates in biosynthesis of the SELL ligand sialyl 6-sulfo Lewis X and in lymphocyte homing to Peyer patches. Has no activity toward O-linked sugars. Its substrate specificity may be influenced by its subcellular location. Sulfates GlcNAc residues at terminal, non-reducing ends of oligosaccharide chains.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Clvs2 ^@ http://purl.uniprot.org/uniprot/Q8BG92 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Binding to PtdIns(3,5)P2 is not required for localization.|||Early endosome membrane|||Forms a complex with clathrin heavy chain and gamma-adaptin.|||Required for normal morphology of late endosomes and/or lysosomes in neurons. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (By similarity).|||The CRAL-TRIO domain is required for targeting to the membrane and for binding PtdIns(3,5)P2.|||clathrin-coated vesicle|||trans-Golgi network membrane http://togogenome.org/gene/10090:Or4c123 ^@ http://purl.uniprot.org/uniprot/Q8VG58 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or52n2 ^@ http://purl.uniprot.org/uniprot/Q8VH00 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc27a3 ^@ http://purl.uniprot.org/uniprot/G3X8Y7|||http://purl.uniprot.org/uniprot/O88561 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Expressed at high levels in adrenal gland, testis and ovary. Expressed at lower levels in adult brain. Found in adrenal cortical cells, spermatocytes and interstitial cells of the testis, theca cells of the ovary, cerebral cortical neurons, and cerebellar Purkinje cells (at protein level).|||Expressed at higher levels in embryonic brain (embryonic days 12-14) than in newborn or adult.|||Mainly functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates (PubMed:15469937, PubMed:15699031). Can mediate the levels of long-chain fatty acids (LCFA) in the cell by facilitating their transport across membranes (PubMed:15699031).|||Mitochondrion membrane http://togogenome.org/gene/10090:Atp8a2 ^@ http://purl.uniprot.org/uniprot/P98200 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atp8a2 and Atp8a1 double mutant mice die soon after birth.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:22912588). Able to translocate phosphatidylserine, but not phosphatidylcholine (By similarity). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE) (PubMed:22912588). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP (By similarity). ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth (PubMed:22641037). Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes. May be involved in vesicle trafficking in neuronal cells. Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival (PubMed:24413176).|||Cell membrane|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit. Interacts with TMEM30A to form a flippase complex.|||Defects in Atp8a2 are the cause of Wabbler-lethal (wl) phenotype. Homozygotes show severe neurological annormalities that include ataxia and body tremors linked to progressive axonal degeneration in several areas of the nervous system.|||Endosome membrane|||Found in testis, heart and brain. Most abundant in testis. Also detected in fetal tissues. Expressed in retinal photoreceptor cells; detected in retina outer nuclear layer and inner segment (at protein level).|||Golgi apparatus membrane|||Membrane|||Photoreceptor inner segment membrane|||Photoreceptor outer segment membrane http://togogenome.org/gene/10090:Nup205 ^@ http://purl.uniprot.org/uniprot/B9EJ54|||http://purl.uniprot.org/uniprot/Q6P9L5|||http://purl.uniprot.org/uniprot/Q6PDG0 ^@ Similarity ^@ Belongs to the NUP186/NUP192/NUP205 family. http://togogenome.org/gene/10090:Mdm4 ^@ http://purl.uniprot.org/uniprot/O35618|||http://purl.uniprot.org/uniprot/Q3UTC9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MDM2/MDM4 family.|||Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts with USP2. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53 (By similarity). Interacts with MDM2, TP53 and TP73.|||In all tissues tested. The short isoform is expressed in a variety of transformed cell lines.|||Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain.|||Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions. The short isoform is a more potent inhibitor of TP53 activity than the long isoform.|||Nucleus|||Phosphorylated. Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation. Phosphorylation at Ser-341 also induces ubiquitination and degradation but to a lower extent (By similarity).|||Region I is sufficient for binding TP53 and inhibiting its G1 arrest and apoptosis functions. It also binds TP73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2.|||Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein (By similarity). http://togogenome.org/gene/10090:Ostc ^@ http://purl.uniprot.org/uniprot/Q78XF5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OSTC family.|||Endoplasmic reticulum|||Membrane|||Specific component of the STT3A-containing form of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. May be involved in N-glycosylation of APP (amyloid-beta precursor protein). Can modulate gamma-secretase cleavage of APP by enhancing endoprotelysis of PSEN1.|||Specific component of the STT3A-containing form of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (By similarity). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity). Interacts with PSEN1 and NCSTN; indicative for an association with the gamma-secretase complex (By similarity). http://togogenome.org/gene/10090:Tab1 ^@ http://purl.uniprot.org/uniprot/Q8CF89 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subunit ^@ Interacts with XIAP and BIRC7. Interacts with TRAF6 and MAP3K7; during IL-1 signaling. Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2. Interacts with TRAF6 and MAPK14; these interactions allow MAPK14 autophosphorylation.|||Key adapter protein that plays an essential role in JNK and NF-kappa-B activation and proinflammatory cytokines production in response to stimulation with TLRs and cytokines (PubMed:12464436, PubMed:28073917). Mechanistically, associates with the catalytic domain of MAP3K7/TAK1 to trigger MAP3K7/TAK1 autophosphorylation leading to its full activation. Similarly, associates with MAPK14 and triggers its autophosphorylation and subsequent activation (PubMed:24037507). In turn, MAPK14 phosphorylates TAB1 and inhibits MAP3K7/TAK1 activation in a feedback control mechanism. Plays also a role in recruiting MAPK14 to the TAK1 complex for the phosphorylation of the TAB2 and TAB3 regulatory subunits (By similarity).|||Lacks several key residues involved in metal-binding and catalytic activity, therefore has lost phosphatase activity.|||Mutant mice die in the late stages of gestation, exhibiting edema and severe embryonic hemorrhage.|||O-GlcNAcylated at Ser-393 is required for full MAP3K7/TAK1 activation upon stimulation with IL-1 or osmotic stress.|||Phosphorylated at all three sites Ser-421, Thr-429 and Ser-436 by MAPK14 when cells were exposed to cellular stresses, or stimulated with TNF-alpha, IL1 or LPS. These phosphorylations inhibit TAK1 activation by a feedback control mechanism. Dephosphorylated by DUSP14 at Ser-436, leading to TAB1-MAP3K7/TAK1 complex inactivation in T-cells.|||Ubiquitinated by MAP3K1 with 'Lys-63'-linked polyubiquitin; leading to activation of TAK1 and of JNK and p38 MAP kinases following EGF and TGF-beta stimulation. Ubiquitinated by ITCH with 'Lys-48'-linked polyubiquitin; leading to proteasomal degradation (By similarity). Ubiquitinated by RNF114 during maternal-to-zygotic transition; leading to degradation (PubMed:28073917). http://togogenome.org/gene/10090:Emid1 ^@ http://purl.uniprot.org/uniprot/Q91VF5 ^@ Developmental Stage|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ At 9.5 dpc it is expressed in the nephric duct, the dorsal neural tube, the epithelia of the branchial arches, and the optic vesicle. In 14.5 dpc embryos, like in earlier ones, it is expressed in the dorsal spinal cord and the brain, where it is restricted to the proliferating ependymal and cortical cell layers. Expression is also detected in smooth muscles of the digestive tract as well as in the epithelia of the salivary gland, the inner ear, and the developing nephrons of kidney. In early embryos, it is expressed in the epithelium of the branchial arches. At 14.5 dpc, Emu1 is restricted to the epithelium in the advanced developing kidney (at 15.5 dpc and later), transcripts are detected in the epithelium of the developing nephrons and in the collecting duct epithelium.|||Homo- or heteromers.|||May be due to a competing acceptor splice site.|||extracellular matrix http://togogenome.org/gene/10090:Cfap53 ^@ http://purl.uniprot.org/uniprot/Q9D439 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CFAP53 family.|||Interacts with PIERCE1 and PIERCE2; the interactions link outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). May play a role in the beating of primary cilia and thereby be involved in the establishment of organ laterality during embryogenesis (By similarity).|||cilium axoneme http://togogenome.org/gene/10090:Gpnmb ^@ http://purl.uniprot.org/uniprot/Q99P91 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 9.5-10.5 dpc, highly expressed in the developing eye, restricted to the outer layer of the retina. At midgestation development, expression gets restricted to the forming retinal pigment layer. At 18.5 dpc, expression remains high in the retinal pigment epithelium and is also observed at the forming iris.|||Belongs to the PMEL/NMB family.|||Cell membrane|||Could be a melanogenic enzyme.|||Early endosome membrane|||May be up-regulated in bone metastatic breast cancer cells.|||Melanosome membrane http://togogenome.org/gene/10090:Rpl32 ^@ http://purl.uniprot.org/uniprot/P62911 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL32 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Pdp1 ^@ http://purl.uniprot.org/uniprot/A2AJP9|||http://purl.uniprot.org/uniprot/A8Y5Q0|||http://purl.uniprot.org/uniprot/A8Y5Q1|||http://purl.uniprot.org/uniprot/Q3UV70 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PP2C family.|||Binds 2 magnesium ions per subunit.|||Catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex.|||Heterodimer of a catalytic (PDP1) and a regulatory (PDPR) subunit.|||Mitochondrion matrix http://togogenome.org/gene/10090:Cd82 ^@ http://purl.uniprot.org/uniprot/P40237|||http://purl.uniprot.org/uniprot/Q3UII2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway.|||Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Highest expression in the spleen and the kidney. Low expression in skeletal muscle and in the heart.|||Interacts directly with IGSF8.|||Membrane http://togogenome.org/gene/10090:Pold4 ^@ http://purl.uniprot.org/uniprot/Q9CWP8 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity. Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb. Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites. Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival.|||Belongs to the DNA polymerase delta subunit 4 family.|||Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities. Within this complex, directly interacts with POLD1 and POLD2. Directly interacts with PCNA, as do POLD1 and POLD3; this interaction stimulates Pol-delta4 polymerase activity. As POLD1 and POLD2, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA, possibly by increasing initiation frequency. Upon genotoxic stress induced by DNA damaging agents or by replication stress, POLD4 is proteolytically degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) that has an increased proofreading activity. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2.|||In response to DNA damage or genotoxic stress, such as UV irradiation or treatment with an alkylating agent, protein expression drastically drops.|||Nucleus|||Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination in response to UV irradiation or treatment with an alkylating agent, leading to proteasomal degradation. This modification is mediated, at least in part, by RNF8.|||Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in response to UV irradiation, leading to proteasomal degradation. This modification is partly mediated by RNF8 and by the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)). Efficient degradation requires the presence of PCNA and is required for the inhibition of fork progression after DNA damage. http://togogenome.org/gene/10090:Mrgprd ^@ http://purl.uniprot.org/uniprot/Q5UCB4|||http://purl.uniprot.org/uniprot/Q91ZB8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed in a subset of sensory neurons that includes nociceptors. Expressed in the subclass of non-peptidergic sensory neurons that are IB4(+) and VR1(-).|||May regulate nociceptor function and/or development, including the sensation or modulation of pain. Functions as a specific membrane receptor for beta-alanine. The receptor couples with G-protein G(q) and G(i) (By similarity).|||Membrane http://togogenome.org/gene/10090:Lyl1 ^@ http://purl.uniprot.org/uniprot/P27792 ^@ Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Nucleus http://togogenome.org/gene/10090:Pax3 ^@ http://purl.uniprot.org/uniprot/P24610|||http://purl.uniprot.org/uniprot/Q3TZM4|||http://purl.uniprot.org/uniprot/Q3UGH9|||http://purl.uniprot.org/uniprot/Q8BRF1 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the paired homeobox family.|||Can bind to DNA as homodimer or a heterodimer with PAX7. Interacts with DAXX. Interacts with PAXBP1; the interaction links PAX3 to a WDR5-containing histone methyltransferase complex. Interacts with TBX18. Interacts with SOX10 (By similarity).|||Expressed during early neurogenesis.|||Nucleus|||The Splotch (Sp) mouse mutant displays defects in neural tube closure in the form of exencephaly and spina bifida. The splotch-delayed (Spd) phenotype is less severe than the other Sp alleles.|||Transcription factor that may regulate cell proliferation, migration and apoptosis. Involved in neural development and myogenesis. Transcriptional activator of MITF, acting synergistically with SOX10 (By similarity). http://togogenome.org/gene/10090:Cyp2g1 ^@ http://purl.uniprot.org/uniprot/Q9WV19 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Or13c7b ^@ http://purl.uniprot.org/uniprot/Q8VGA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pkhd1l1 ^@ http://purl.uniprot.org/uniprot/Q80ZA4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Adipoq ^@ http://purl.uniprot.org/uniprot/Q60994 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During hormone-induced adipose differentiation and activated by insulin.|||HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagen-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes.|||HMW-complex blood contents are higher in females than in males, are increased in males by castration and decreased again upon subsequent testosterone treatment, which blocks HMW-complex secretion.|||Homomultimer (PubMed:23209641). Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW) (PubMed:23209641). The HMW-complex assembly is also modulated by the degree of lysine hydroxylation and glycosylation (PubMed:23209641). LMW, MMW and HMW complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW complex binds to FGF2. Interacts with CTRP9 via the C1q domain (heterotrimeric complex) (PubMed:18787108).|||Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW.|||O-glycosylated. Not N-glycosylated (By similarity) O-linked glycans on hydroxylysine residues consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups (By similarity). O-linked glycosylation in the N-terminal is disialylated with the structure Neu5Acalpha2->8Neu5Acalpha2->3Gal. Sialylated by alpha 2,8-sialyltransferase III.|||Polymerization and secretion of adiponectin is inhibited by succination of cysteine residues by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues.|||Secreted|||Succination of Cys-39 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits polymerization and secretion of adiponectin. Adiponectin is a major target for succination in both adipocytes and adipose tissue of diabetic mice. It was proposed that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes.|||Synthesized exclusively by adipocytes and secreted into plasma. http://togogenome.org/gene/10090:Nfasc ^@ http://purl.uniprot.org/uniprot/E9PW06|||http://purl.uniprot.org/uniprot/E9Q171|||http://purl.uniprot.org/uniprot/Q6P6Q1|||http://purl.uniprot.org/uniprot/Q6ZQ54|||http://purl.uniprot.org/uniprot/Q810U3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.|||Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions.|||Cell membrane|||Homophilic adhesion is primarily mediated by the interaction of the second Ig-like domains.|||Horseshoe-shaped homodimer. Probable constituent of a NFASC/NRCAM/ankyrin-G complex. Associates with the sodium channel beta-1 (SCN1B) and beta-3 (SCN3B) subunits. Interacts with GLDN/gliomedin (By similarity). Interacts with MYOC. http://togogenome.org/gene/10090:Hltf ^@ http://purl.uniprot.org/uniprot/Q6PCN7 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family. RAD16 subfamily.|||Cytoplasm|||Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle.|||Expressed in the heart from 11.5 dpc. Gradually increases in skeletal muscle to 18.5 dpc.|||Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity. This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA (By similarity).|||Interacts with SP1 and SP3 independently of DNA; the interaction with these transcriptional factors may be required for basal transcription of target genes. Interacts with EGR1; the interaction requires prior binding to DNA and represses c-Rel via a DNA looping mechanism. Interacts with GATA4. Interacts with PCNA; the interaction promotes polyubiquitination of PCNA through association with the UBE2B-RAD18 and UBE2V2-UBE2N ubiquitin ligase complexes. Interacts with RAD18, SHPRH, UBE2V2 and UBE2N (By similarity).|||Intron retention.|||Nucleus|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Tctn2 ^@ http://purl.uniprot.org/uniprot/Q2MV57 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc, expressed in the neural tube, most notably in the rhombomere of the future hindbrain. By 10.5 dpc, expressed throughout the brain, the length of the neural tube, the growing edge of the limb buds, heart, and eyes. Strong expression is observed in the kidney at 14.5 dpc.|||Belongs to the tectonic family.|||Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for hedgehog signaling transduction.|||Membrane|||Mice have ventricular septal defects and can display right-sided stomach. The embryos exhibit microphthalmia, cleft palate and polydactyly. Embryos lack also nodal cilia. Cilia in neural tubes are scarce and morphologically defective, and failed to elongate axonemes. Basal bodies dock to the plasma membrane in Tctn2 null neural epithelium. No Arl13b ciliary staining in defective Tctn2 embryos perineural mesenchyme suggesting that, as in Tctn1 null mutants, defective Tctn2 cilia lack Arl13b. Tctn1 and Tctn2 share a common function, with both affecting ciliogenesis in a tissue-specific manner.|||Part of the tectonic-like complex (also named B9 complex).|||Significant expression is observed in brain, kidney and eye.|||cilium basal body http://togogenome.org/gene/10090:Rhbdd3 ^@ http://purl.uniprot.org/uniprot/B7ZNJ8|||http://purl.uniprot.org/uniprot/Q8BP97 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Uvssa ^@ http://purl.uniprot.org/uniprot/Q9D479 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UVSSA family.|||Chromosome|||Factor involved in transcription-coupled nucleotide excision repair (TC-NER), a mechanism that rapidly removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. Facilitates the ubiquitination of the elongating form of RNA polymerase II (RNA pol IIo) at DNA damage sites, thereby promoting RNA pol IIo backtracking and access by the TC-NER machinery to lesion sites. Acts by promoting stabilization of ERCC6 by recruiting deubiquitinating enzyme USP7 to TC-NER complexes, preventing UV-induced degradation of ERCC6 by the proteasome. Also facilitates transfer of TFIIH to RNA polymerase II. Not involved in processing oxidative damage.|||Interacts with the elongating form of RNA polymerase II (RNA pol IIo) during transcription stress. Interacts with the TFIIH complex during transcription stress. Interacts with ERCC6. Interacts with ERCC8. Interacts with USP7.|||Monoubiquitinated at Lys-416 in response to transcription stress; this promotes efficient transfer of TFIIH to stalled RNA polymerase II. http://togogenome.org/gene/10090:Pierce1 ^@ http://purl.uniprot.org/uniprot/Q5BN45 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8 dpc, strongly expressed in the node area (PubMed:27305836). May be up-regulated during progression from G1 to S phase of the cell cycle. Maximal expression in S or G2 phase.|||Belongs to the PIERCE1 family.|||By p53/TP53. Protein levels are stabilized following gamma-irradiation.|||Expressed in brain, lung, kidney and testis.|||Interacts with CFAP53, ODAD1 and ODAD3; the interactions link the outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.|||Microtubule inner protein involved in the attachment of outer dynein arms (ODAs) to dynein-decorated doublet microtubules (DMTs) in cilia axoneme (PubMed:34715025). Functions at the initial step of left-right asymmetry specification of the visceral organs (PubMed:27305836).|||Mutant mice exhibit severe laterality defects, including situs inversus totalis and heterotaxy with randomized situs and left and right isomerisms (PubMed:27305836, PubMed:34715025). They show partial embryonic lethality associated with heterotaxia (PubMed:27305836, PubMed:34715025). The motility of tracheal cilia in adult mice is also affected (PubMed:34715025). At 8 dpc, they have a reduced beat frequency of nodal cilia (PubMed:34715025). 50% of tracheal cilia axonemes have missing dynein arms (PubMed:34715025). Double PIERCE1 and PIERCE2 mutants show high levels of embryonic and pre-weaning lethality. The few mice that survive birth display hydrocephalus and laterality abnormalities, dying by 20 days of age (PubMed:34715025).|||cilium axoneme http://togogenome.org/gene/10090:Ndufa1 ^@ http://purl.uniprot.org/uniprot/O35683|||http://purl.uniprot.org/uniprot/Q545K0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA1 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Vmn2r99 ^@ http://purl.uniprot.org/uniprot/H3BK37 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Phlda3 ^@ http://purl.uniprot.org/uniprot/Q9WV95 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PHLDA3 family.|||Cytoplasm|||Expressed in extraembryonic tissues and placenta at 11.5 and 18.5 dpc (at protein level). Expression continues throughout gestation and is strong in adult lung (at protein level).|||Membrane|||Mice are viable and fertile, and show normal placenta and embryonic weights.|||The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling (By similarity).|||Widely expressed in fetal tissues, with the exception of liver. Strongly expressed in adult skeletal muscle and lung. Widely expressed at lower levels in other adult tissues, with weakest expression in liver and spleen.|||p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting AKT1 translocation to the cellular membrane and activation. Contributes to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May act as a tumor suppressor (By similarity). http://togogenome.org/gene/10090:Snapc2 ^@ http://purl.uniprot.org/uniprot/Q91XA5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC2 interacts with TBP and SNAPC4 (By similarity).|||Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box (By similarity). http://togogenome.org/gene/10090:Capn5 ^@ http://purl.uniprot.org/uniprot/O08688|||http://purl.uniprot.org/uniprot/Q3TPL4 ^@ Function|||Similarity ^@ Belongs to the peptidase C2 family.|||Calcium-regulated non-lysosomal thiol-protease. http://togogenome.org/gene/10090:Or4f57 ^@ http://purl.uniprot.org/uniprot/Q7TQX0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gja1 ^@ http://purl.uniprot.org/uniprot/A0A654ICD2|||http://purl.uniprot.org/uniprot/P23242 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||A connexon is composed of a hexamer of connexins. Interacts with CSNK1D (By similarity). Interacts with RIC1/CIP150 (By similarity). Interacts (via C-terminus) with TJP1 (By similarity). Interacts (via C-terminus) with SRC (via SH3 domain) (By similarity). Interacts (not ubiquitinated) with UBQLN4 (via UBA domain). Interacts with CNST. Interacts with SGSM3. Interacts with NOV (By similarity). Interacts with TMEM65 (PubMed:26403541).|||Acetylated in the developing cortex; leading to delocalization from the cell membrane.|||At 7.5 dpc, expressed in the embryo, but not in the extraembryonic region containing the ectoplacental cone.|||Belongs to the connexin family. Alpha-type (group II) subfamily.|||Cell membrane|||Connexin 43 is possibly the ATP-induced pore of mouse macrophages.|||Endoplasmic reticulum|||Expressed in heart, non-sensory epithelial cells, and in fibrocytes of the spiral ligament and the spiral limbus. Expressed in bladder smooth muscle cells (at protein level). Expressed in astrocytes (at protein level) (PubMed:15213231).|||Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract. May play a role in cell growth inhibition through the regulation of NOV expression and localization (PubMed:15181016). Plays an essential role in gap junction communication in the ventricles (PubMed:26403541).|||In bladder smooth muscle cells, exhibits night/day variations with low levels during the sleep phase, at circadian time (CT) 4-12 (at protein level). Down-regulation during the night allows increase in bladder capacity, avoiding disturbance of sleep by micturition. Expression starts to increase around CT12 and forms a plateau during the active phase (CT16-24) (at protein level). Circadian transcription is activated by NR1D1. Up-regulated by SP1 and SP3.|||Membrane|||Mutant mice die shortly after birth.|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity. Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).|||S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication.|||Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the plasma membrane. May be desumoylated by SENP1 or SENP2 (By similarity).|||gap junction http://togogenome.org/gene/10090:Mstn ^@ http://purl.uniprot.org/uniprot/O08689|||http://purl.uniprot.org/uniprot/Q540E2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts specifically as a negative regulator of skeletal muscle growth.|||Belongs to the TGF-beta family.|||Expressed specifically in developing and adult skeletal muscle. Weak expression in adipose tissue.|||First detected 9.5 dpc in one-third of developing somites. At 10.5 dpc, expressed in the myotome compartment of somites. At later stages of development, detected in a wide range of developing muscles. Expression continues in adulthood.|||Homodimer; disulfide-linked (PubMed:19644449). Interacts with WFIKKN2, leading to inhibit its activity (PubMed:12595574). Interacts with FSTL3 (PubMed:22052913).|||Homodimer; disulfide-linked. Interacts with WFIKKN2, leading to inhibit its activity. Interacts with FSTL3.|||Mutant animals exhibit muscle hypertrophy.|||Secreted|||Synthesized as large precursor molecule that undergoes proteolytic cleavage to generate an N-terminal propeptide and a disulfide linked C-terminal dimer, which is the biologically active molecule. The circulating form consists of a latent complex of the C-terminal dimer and other proteins, including its propeptide, which maintain the C-terminal dimer in a latent, inactive state. Ligand activation requires additional cleavage of the prodomain by a tolloid-like metalloproteinase (PubMed:14671324). http://togogenome.org/gene/10090:Sprr2e ^@ http://purl.uniprot.org/uniprot/O70556 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane (By similarity).|||Cytoplasm|||During early pregnancy, uterine expression is markedly increased at 1 dpc and 2 dpc, with levels decreasing from 3 dpc onwards.|||Expressed in uterus.|||Up-regulated by estrogen in the uterus of ovariectomized animals, with strongly increased expression detected in luminal epithelial cells at 6 and 12 hours after hormone injection. http://togogenome.org/gene/10090:4933405O20Rik ^@ http://purl.uniprot.org/uniprot/Q8BPC6 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the isocitrate and isopropylmalate dehydrogenases family.|||Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) ion per subunit.|||Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.|||Mitochondrion|||Regulatory subunit which plays a role in the allosteric regulation of the enzyme catalyzing the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal activity but the full activity of the heterotetramer (containing two subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly and cooperative function of both heterodimers.|||The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits. http://togogenome.org/gene/10090:Ces2e ^@ http://purl.uniprot.org/uniprot/Q8BK48 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Carboxylesterase that catalyzes the hydrolysis of pyrethroids pesticides. Hydrolyzes trans-permethrin at a rate about 22-fold higher than cis-permethrin. Also hydrolyzes trans-cypermethrin. Hydrolyzes retinyl esters (By similarity).|||Glycosylated.|||Microsome http://togogenome.org/gene/10090:Or51l4 ^@ http://purl.uniprot.org/uniprot/Q9EQQ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myoc ^@ http://purl.uniprot.org/uniprot/O70624|||http://purl.uniprot.org/uniprot/Q05AC1 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell projection|||Cytoplasmic vesicle|||Endoplasmic reticulum|||Expressed in ciliary body, iris, retina, trabecular network and sclera but not in lens or cornea. Also expressed strongly in skeletal muscle and weakly in heart, brain, testis, liver, kidney, thyroid and epididymis. No expression detected in embryo. Expressed in sciatic nerve.|||Glycosylated.|||Golgi apparatus|||Homodimer (via N-terminus). Interacts with OLFM3, FN1, NRCAM, GLDN and NFASC. Interacts (via N-terminus) with MYL2. Interacts with SFRP1, FRZB, FZD7, FZD10, FZD1 and WIF1; regulates Wnt signaling. Interacts with SNTA1; regulates muscle hypertrophy (PubMed:22371502). Interacts with ERBB2 and ERBB3; activates ERBB2-ERBB3 signaling pathway (PubMed:23897819). Interacts with SNCG; affects its secretion and its aggregation (PubMed:16392033).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice lacking Myoc are viable, fertile and show no significant differences in intraocular pressure or clinical signs of glaucoma. They also show a reduction in cortical bone thickness as well as trabecular volume.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||Mitochondrion outer membrane|||Palmitoylated.|||Rough endoplasmic reticulum|||Secreted|||Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling (By similarity). Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling (PubMed:23629661). Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling (PubMed:23897819). Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex (PubMed:22371502). Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork (By similarity).|||Undergoes a calcium-dependent proteolytic cleavage at Gln-212 by CAPN2 in the endoplasmic reticulum. The result is the production of two fragments, one of 35 kDa containing the C-terminal olfactomedin-like domain, and another of 20 kDa containing the N-terminal leucine zipper-like domain (By similarity).|||Variant Ala-164 is found in strain BALB/cJ which has a low intraocular pressure (PubMed:9588210, PubMed:9675094). Variant Thr-164 is found in strains C3H/HeJ and C57BL/6J, two strains which have a relatively high intraocular pressure (PubMed:9588210, PubMed:9548973, PubMed:9680392).|||cilium|||extracellular exosome|||extracellular matrix|||extracellular space http://togogenome.org/gene/10090:Rnd3 ^@ http://purl.uniprot.org/uniprot/P61588 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.|||Golgi apparatus membrane|||Interacts with UBXD5 (By similarity). Binds ROCK1.|||Ubiquitous. http://togogenome.org/gene/10090:Dusp23 ^@ http://purl.uniprot.org/uniprot/Q6NT99 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Nucleus|||Protein phosphatase that mediates dephosphorylation of proteins phosphorylated on Tyr and Ser/Thr residues. In vitro, it can dephosphorylate p44-ERK1 (MAPK3) but not p54 SAPK-beta (MAPK10) in vitro. Able to enhance activation of JNK and p38 (MAPK14).|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Or52ac1 ^@ http://purl.uniprot.org/uniprot/E9Q252 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or7a38 ^@ http://purl.uniprot.org/uniprot/E9Q5G9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Robo1 ^@ http://purl.uniprot.org/uniprot/O89026 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. ROBO family.|||Cell membrane|||Detected in embryonic thalamus neurons (at protein level) (PubMed:24560577). Expressed in embryonal spinal chord. Expressed in embryonal lung, and in adult lung bronchial epithelial cells of large proximal airways.|||Earliest and highest expression at 11 dpc. Expression is detected in developing somits, brain, neural tube, and pericardiac mesenchyme. By in situ hybridization is detected in marginal zones bordering the mitotically active periventricular region, weakly extending to the ventral aspect impinging on motor neuron columns. Also detected in the ventral third of the developing neural tube, and in spinal cord throughout the full length of the neural tube. Also detected at 17.5 dpc in lung mesenchyme. Expressed at 11.5 dpc in spinal cord, predominantly localized to postcrossing commissural axons.|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Homodimer. Dimerization is mediated by the extracellular domain and is independent of SLIT liganding (By similarity). Interacts with SLIT1 (PubMed:10433822) Interacts with SLIT2 (By similarity). Interacts with FLRT3 (PubMed:24560577). Interacts with MYO9B (via Rho-GAP domain) (By similarity).|||Mice show defects in commissural axon guidance in spinal cord including midline recrossing and an altered lateral and ventral funiculi projection. The phenotype resembles that of a SLIT1;SLIT2;SLIT3 triple mutant. They also mimick a naturally occurring human homozygous deletion mutant detected in a small lung cancer cell line, frequently die at birth by respiratory failure with accompanying abnormal lung histology. Surviving mice develop bronchial hyperplasia.|||Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development (PubMed:10433822, PubMed:24560577). Interaction with the intracellular domain of FLRT3 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex (By similarity). Plays a role in the regulation of cell migration via its interaction with MYO9B; inhibits MYO9B-mediated stimulation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (By similarity). May be required for lung development (PubMed:11734623).|||Ubiquitinated. May be deubiquitinated by USP33.|||axon http://togogenome.org/gene/10090:Rmdn1 ^@ http://purl.uniprot.org/uniprot/Q9DCV4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RMDN family.|||Cytoplasm|||Interacts with microtubules.|||spindle|||spindle pole http://togogenome.org/gene/10090:Kat6b ^@ http://purl.uniprot.org/uniprot/A0A5F8MQ39|||http://purl.uniprot.org/uniprot/Q3UH94|||http://purl.uniprot.org/uniprot/Q501M5|||http://purl.uniprot.org/uniprot/Q8BRB7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoacetylation at Lys-633 is required for proper function.|||Belongs to the MYST (SAS/MOZ) family.|||Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with RUNX1 and RUNX2.|||Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (By similarity). Involved in cerebral cortex development.|||Mice have a low body weight, craniofacial abnormalities, and defects in cortex development. Mice carrying a gene trap insertion in the gene, produces approximately 5% of the normal amount of mRNA. The hypomorphic mutant displays a number of defects that mirror SBBYSS syndrome, although the phenotype is milder. Mice are of normal size at birth but fail to thrive and have brain developmental defects as well as craniofacial defects. Observed abnormalities include short and narrow palpebral fissures, low set ears, and malocclusion. Similar to individuals with SBBYSS, mice carrying the gene trap insertion have long, slender feet and disproportionally long first digits.|||Nucleus|||Probable intron retention.|||Strongly expressed in the ventricular zone of the developing cerebral cortex.|||The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Sdr9c7 ^@ http://purl.uniprot.org/uniprot/Q8K3P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Cytoplasm|||Displays weak conversion of all-trans-retinal to all-trans-retinol in the presence of NADH. Has apparently no steroid dehydrogenase activity (By similarity).|||Highly expressed in liver. http://togogenome.org/gene/10090:Spinkl ^@ http://purl.uniprot.org/uniprot/Q8CEK3 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By testosterone.|||Does not function as an inhibitor of trypsin, chymotrypsin, subtilisin or elastase. Binds sperm and enhances sperm motility. May act as a decapacitation factor, suppresses BSA-stimulated sperm capacitation and blocks sperm-oocyte interactions in vitro.|||First appears at low levels in 3 week old mice. Levels increase rapidly after 4 weeks, highest levels are reached in 8 week old mice.|||Luminal fluid and mucosal folds of the seminal vesicles (at protein level). Not detected in brain, heart, lung, liver, kidney, stomach, small intestine, muscle, skin, thymus, placenta or bladder.|||Secreted http://togogenome.org/gene/10090:Hdac9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1F3|||http://purl.uniprot.org/uniprot/A0A1B0GR65|||http://purl.uniprot.org/uniprot/A0A1B0GRH0|||http://purl.uniprot.org/uniprot/A0A1B0GSQ5|||http://purl.uniprot.org/uniprot/A0A668KM95|||http://purl.uniprot.org/uniprot/Q99N13 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, expressed in heart, skeletal muscle and neural lineages. At 11.5d pc, expressed in heart, dorsal root ganglia and neural tube. At 12.5 dpc, expressed in heart, skeletal muscle, dorsal root ganglia, neural tube and retina. Strongly up-regulated in muscle between 14 and 19 dpc as a result of motor innervation.|||Belongs to the histone deacetylase family. HD type 2 subfamily.|||By MEF2 during muscle differentiation. Down-regulated by muscle denervation. Down-regulated by trichostatin A or sodium butyrate, and during neuronal apoptosis (at protein level).|||Devoided of intrinsic deacetylase activity, promotes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) by recruiting HDAC1 and HDAC3. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription, inhibits skeletal myogenesis and may be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.|||Expressed at high levels in heart, brain and spleen. Expressed in skeletal muscle.|||Homodimer. Interacts with ETV6 (By similarity). Interacts with MEF2, HDAC1, HDAC3, HDAC4, HDAC5, CTBP1 and MAPK10. The phosphorylated form interacts with 14-3-3. Interacts with FOXP3 in the absence of T-cell stimulation (By similarity).|||Mice do not present any abnormality at early age but develop cardiac hypertrophy by eight months of age.|||Nucleus|||Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-binding, impairs interaction with MEF2, and antagonizes antimyogenic activity. Phosphorylated on Ser-240 by DYRK1B; which impairs nuclear accumulation. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import.|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events.|||Sumoylated. http://togogenome.org/gene/10090:Socs6 ^@ http://purl.uniprot.org/uniprot/Q9JLY0 ^@ Domain|||Function|||Subunit ^@ Interacts with KIT (phosphorylated) (By similarity). Interacts with RBCK1. Interacts with phosphorylated IRS4. Interacts with PIM3.|||SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Regulates KIT degradation by ubiquitination of the tyrosine-phosphorylated receptor (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Gigyf1 ^@ http://purl.uniprot.org/uniprot/Q99MR1 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GIGYF family.|||Interacts with GRB10 (PubMed:12771153). This transient binding is increased under IGF1 stimulation and leads to recruitment of GIGYF1/GRB10 complex to IGF1 receptor (PubMed:12771153). Interacts with DDX6 (By similarity).|||May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1.|||Ubiquitous. Lower expression in skeletal muscle, liver and testis. http://togogenome.org/gene/10090:Elp6 ^@ http://purl.uniprot.org/uniprot/Q8BK75 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the ELP6 family.|||Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6.|||Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (By similarity). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity). Involved in cell migration (PubMed:22854966).|||Early embryonic lethality.|||Expressed throughout the cerebellum.|||The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification. http://togogenome.org/gene/10090:Mrps7 ^@ http://purl.uniprot.org/uniprot/Q80X85 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS7 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Or4f14b ^@ http://purl.uniprot.org/uniprot/Q7TQX1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam167b ^@ http://purl.uniprot.org/uniprot/P17257 ^@ Caution|||Similarity ^@ Belongs to the FAM167 (SEC) family.|||Was originally thought to originate from human. http://togogenome.org/gene/10090:Sprr2b ^@ http://purl.uniprot.org/uniprot/A9JTY7 ^@ Similarity ^@ Belongs to the cornifin (SPRR) family. http://togogenome.org/gene/10090:Synpr ^@ http://purl.uniprot.org/uniprot/Q8BGN8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptophysin/synaptobrevin family.|||Intrinsic membrane protein of small synaptic vesicles. Probable vesicular channel protein (By similarity).|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Fhip2b ^@ http://purl.uniprot.org/uniprot/Q80YR2 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Able to activate MAPK/ERK and TGFB signaling pathways (By similarity). May regulate the activity of genes involved in intestinal barrier function and immunoprotective inflammation (PubMed:31862898). May play a role in cell proliferation (By similarity).|||Belongs to the FHIP family.|||Expressed in colon.|||Mutants are viable, fertile with no apparent defects. Mice are more susceptibility to colitis induced by dextran sodium sulfate (DSS) than wild type littermates (PubMed:31862898). They display significantly increased tumor burden compared with WT mice assessed in colitis-associated colorectal cancer model induced by azoxymethane (AOM)-DSS (PubMed:31862898). http://togogenome.org/gene/10090:Tmem107 ^@ http://purl.uniprot.org/uniprot/Q9CPV0 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit ^@ Defect in TMEM107 is the cause of the schlei phenotype. Schlei mice display Shh-related defects including, preaxial polydactyly, exencephaly, and disrupted ventral neural tube patterning. Mice shown decreased numbers of cilia in several developing tissues and organs. However, nodal cilia appear normal in schlei mutants and subsequently, no left-right defects are observed.|||Membrane|||Part of the tectonic-like complex (also named B9 complex). Interacts with TMEM237, TMEM231, MKS1 and TMEM216.|||Plays a role in cilia formation and embryonic patterning. Requires for normal Sonic hedgehog (Shh) signaling in the neural tube and acts in combination with GLI2 and GLI3 to pattern ventral and intermediate neuronal cell types. During ciliogenesis regulates the ciliary transition zone localization of some MKS complex proteins (PubMed:26595381, PubMed:26518474).|||cilium http://togogenome.org/gene/10090:Fkbp3 ^@ http://purl.uniprot.org/uniprot/Q62446 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FKBP-type PPIase family.|||FK506- and rapamycin-binding proteins (FKBPs) constitute a family of receptors for the two immunosuppressants which inhibit T-cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. PPIases accelerate the folding of proteins (By similarity).|||Inhibited preferentially by rapamycin over FK506.|||Nucleus http://togogenome.org/gene/10090:Or5b112 ^@ http://purl.uniprot.org/uniprot/Q8VFW4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccdc8 ^@ http://purl.uniprot.org/uniprot/D3YZV8 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Component of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats); may link the 3M complex to histone deacetylases including HDAC4 and HDAC5.|||Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer. Required for localization of CUL7 to the centrosome.|||Cytoplasm|||Despite its name, does not contain a coiled coil domain.|||The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2.|||centrosome http://togogenome.org/gene/10090:Gm21683 ^@ http://purl.uniprot.org/uniprot/Q5FWB5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Acp7 ^@ http://purl.uniprot.org/uniprot/B2RRA7|||http://purl.uniprot.org/uniprot/Q8BX37 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the metallophosphoesterase superfamily. Purple acid phosphatase family.|||Binds 1 Fe cation per subunit.|||Binds 1 zinc ion per subunit.|||Secreted http://togogenome.org/gene/10090:Tagap1 ^@ http://purl.uniprot.org/uniprot/P0CAX8 ^@ Caution ^@ Previously thought to be the same gene as Tagap. These are distinct loci that encode proteins with identical C-termini but each with a unique N-terminus. http://togogenome.org/gene/10090:Ascc3 ^@ http://purl.uniprot.org/uniprot/E9PZJ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATPase involved both in DNA repair and rescue of stalled ribosomes. 3'-5' DNA helicase involved in repair of alkylated DNA: promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3-methylcytosine (3mC) within double-stranded regions. Also involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation. Drives the splitting of stalled ribosomes that are ubiquitinated in a ZNF598-dependent manner, as part of the ribosome quality control trigger (RQT) complex. Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation.|||Belongs to the helicase family.|||Identified in the ASCC complex that contains ASCC1, ASCC2 and ASCC3. Functions as scaffolding subunit that interacts directly with both ASCC1 and ASCC2. Interacts directly with ALKBH3, and thereby recruits ALKBH3 to the ASCC complex. Part of the ASC-1/TRIP4 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3. Part of the RQT (ribosome quality control trigger) complex, that contains ASCC2, ASCC3 and TRIP4. Associates with ribosomes; recruited to collided ribosomes. Interacts with ZCCHC4. Interacts with ZNF598. Interacts with RPS3.|||Nucleus|||Nucleus speckle|||cytosol http://togogenome.org/gene/10090:Mrpl3 ^@ http://purl.uniprot.org/uniprot/Q99N95 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL3 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Tagln ^@ http://purl.uniprot.org/uniprot/P37804 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Actin cross-linking/gelling protein.|||Belongs to the calponin family.|||By growth factors.|||Cytoplasm http://togogenome.org/gene/10090:Or6c66b ^@ http://purl.uniprot.org/uniprot/Q7TRH9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rtl5 ^@ http://purl.uniprot.org/uniprot/Q5DTT4 ^@ Miscellaneous ^@ RTL5 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes. http://togogenome.org/gene/10090:Ocln ^@ http://purl.uniprot.org/uniprot/B2RS24|||http://purl.uniprot.org/uniprot/Q61146 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELL/occludin family.|||Cell membrane|||Dephosphorylated by PTPRJ (By similarity). May be phosphorylated by PKC during translocation to cell-cell contacts.|||Found diffusely on the lateral membranes of Sertoli cells in the early prepubertal period. With development, became gradually concentrated at the most basal regions of Sertoli cells.|||Interacts with TJP1/ZO1. Interacts with VAPA. Interacts with CLDN1, CLDN6, CLDN9, CLDN11, CLDN12 and CLDN17. Interacts with PLSCR1. Interacts with LSR, ILDR1 and ILDR2. Interacts with TJP2/ZO2 (PubMed:10026224).|||Localized at tight junctions of both epithelial and endothelial cells. Highly expressed in the testis, kidney, lung, liver and brain. Not detected in skeletal muscle, spleen and heart.|||May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.|||Membrane|||Mice have a complex phenotype including abnormalities of salivary gland, gastric epithelium, bone, testis and intracranial calcification.|||The C-terminal is cytoplasmic and is important for interaction with ZO-1. Necessary for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction (By similarity).|||tight junction http://togogenome.org/gene/10090:Nab1 ^@ http://purl.uniprot.org/uniprot/A0A087WSU4|||http://purl.uniprot.org/uniprot/Q61122 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2.|||Belongs to the NAB family.|||Homomultimers may associate with EGR1 bound to DNA.|||In day 16 embryo highest levels in forebrain, thymus, salivary gland and cartilage.|||Nucleus|||The NAB conserved domain 1 (NCD1) interacts with EGR1 inhibitory domain and mediates multimerization.|||The NAB conserved domain 2 (NCD2) is necessary for transcriptional repression.|||Widely expressed in adult. In day 16 embryo highest levels in forebrain, thymus, salivary gland and cartilage. http://togogenome.org/gene/10090:Ctdspl ^@ http://purl.uniprot.org/uniprot/P58465 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds 1 Mg(2+) ion per monomer.|||Monomer. Interacts with REST.|||Nucleus|||Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells (By similarity). http://togogenome.org/gene/10090:Hsp90ab1 ^@ http://purl.uniprot.org/uniprot/P11499|||http://purl.uniprot.org/uniprot/Q71LX8 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 90 family.|||Cell membrane|||Cleaved following oxidative stress resulting in HSP90AB1 protein radicals formation; disrupts the chaperoning function and the degradation of its client proteins.|||Cytoplasm|||Dynein axonemal particle|||ISGylated.|||In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state.|||Melanosome|||Methylated by SMYD2; facilitates dimerization and chaperone complex formation; promotes cancer cell proliferation.|||Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery. Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription. Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10.|||Monomer (By similarity). Homodimer (PubMed:8289821). Forms a complex with CDK6 and CDC37. Interacts with UNC45A; binding to UNC45A involves 2 UNC45A monomers per HSP90AB1 dimer (By similarity). Interacts with CHORDC1 (PubMed:15642353). Interacts with DNAJC7. Interacts with FKBP4. May interact with NWD1. Interacts with SGTA. Interacts with HSF1 in an ATP-dependent manner. Interacts with MET; the interaction suppresses MET kinase activity. Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2. Interacts with STUB1 and SMAD3. Interacts with XPO1 and AHSA1. Interacts with BIRC2. Interacts with KCNQ4; promotes cell surface expression of KCNQ4. Interacts with BIRC2; prevents auto-ubiquitination and degradation of its client protein BIRC2. Interacts with NOS3. Interacts with AHR; interaction is inhibited by HSP90AB1 phosphorylation on Ser-226 and Ser-255. Interacts with STIP1 and CDC37; upon SMYD2-dependent methylation. Interacts with JAK2 and PRKCE; promotes functional activation in a heat shock-dependent manner. Interacts with HSP90AA1; interaction is constitutive. HSP90AB1-CDC37 chaperone complex interacts with inactive MAPK7 (via N-terminal half) in resting cells; the interaction is MAP2K5-independent and prevents from ubiquitination and proteasomal degradation. Interacts with CDC25A; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression. Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation. Interacts with TGFB1 processed form (LAP); inhibits latent TGFB1 activation (By similarity). Interacts with TRIM8; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1 (PubMed:21689689). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (PubMed:27686098). Interacts with PDCL3 (PubMed:27496612). Interacts with TTC4 (via TPR repeats) (By similarity). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (By similarity).|||Nucleus|||Phosphorylation at Tyr-301 by SRC is induced by lipopolysaccharide. Phosphorylation at Ser-226 and Ser-255 inhibits AHR interaction.|||S-nitrosylated; negatively regulates the ATPase activity.|||Secreted|||The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.|||Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro). http://togogenome.org/gene/10090:Fam205c ^@ http://purl.uniprot.org/uniprot/Q80YD3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Ccp110 ^@ http://purl.uniprot.org/uniprot/Q7TSH4 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with CALM1, CETN2, CEP76, CEP104, CEP290 and TALPID3 (By similarity). Interacts with CEP97 (PubMed:35301795). Seems to associate with discrete CETN2, CEP97 and CEP290-containing complexes (By similarity). Interacts with NEURL4 and CCNF; these interactions are not mutually exclusive and both lead to CCP110 ubiquitination and proteasome-dependent degradation (By similarity). Via its interaction with NEURL4, may indirectly interact with HERC2 (By similarity). Interacts with KIF24, leading to its recruitment to centrioles (By similarity). Interacts with USP20 and USP33 (By similarity). Interacts with MPHOSPH9 (By similarity). Interacts (via N-terminal region) with ENKD1 (via central region); ENKD1 competes with CEP97 for binding to CCP110, destabilizing the interaction between CP110 and CEP97 which promotes the removal of CCP110 and CEP97 from the mother centriole and allows the initiation of ciliogenesis (PubMed:35301795).|||Lethal within a few hours after birth with multiple defects in organogenesis. Mice show an early block in cilia formation and a phenotype reminiscent of human short rib-polydactyly syndrome.|||Necessary for centrosome duplication at different stages of procentriole formation. Acts as a key negative regulator of ciliogenesis in collaboration with CEP97 by capping the mother centriole thereby preventing cilia formation (PubMed:23141541). Also involved in promoting ciliogenesis. May play a role in the assembly of the mother centriole subdistal appendages (SDA) thereby effecting the fusion of recycling endosomes to basal bodies during cilia formation (PubMed:26965371). Required for correct spindle formation and has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CETN2 (By similarity).|||Phosphorylated by CDKs.|||Ubiquitinated by the SCF(CCNF) during G2 phase, leading to its degradation by the proteasome and preventing centrosome reduplication. Deubiquitinated by USP33 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate (By similarity).|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Tmsb15l ^@ http://purl.uniprot.org/uniprot/Q8C0W0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the thymosin beta family.|||cytoskeleton http://togogenome.org/gene/10090:Ecel1 ^@ http://purl.uniprot.org/uniprot/Q3TX93|||http://purl.uniprot.org/uniprot/Q9JMI0 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ According to a report, mice die of respiratory failure shortly after birth (PubMed:10400672). According to a second report, mice exhibit perturbed terminal branching of motor neurons to the endplate of skeletal muscles, resulting in poor formation of the neuromuscular junction (PubMed:23261301).|||Belongs to the peptidase M13 family.|||Binds 1 zinc ion.|||May contribute to the degradation of peptide hormones and be involved in the inactivation of neuronal peptides.|||Membrane http://togogenome.org/gene/10090:Ppp2r5a ^@ http://purl.uniprot.org/uniprot/Q6PD03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphatase 2A regulatory subunit B56 family.|||Cytoplasm|||Nucleus|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1 (By similarity).|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.|||Widely expressed with highest levels in thymus and ovary.|||centromere http://togogenome.org/gene/10090:Rgs14 ^@ http://purl.uniprot.org/uniprot/P97492 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in germinal vesicle oocytes, not in metaphase II oocytes. Expressed in embryo from 8.5 through 16.5 dpc (at protein level). Expressed in the zygote through to the blastocyst stage. Expressed in area lateral to the rhombencephalic floor plate at 12 dpc. Expressed in the anterior region of the brain, including the telencephalic olfactive nuclei and the hippocampus anlage at 17 dpc.|||Expressed in pyramidal neurons of the CA1, CA2 and fasciola cinerea (FC) subregions of the hippocampus and in the olfactory cortex (at protein level). Expressed in brain, spleen, heart, liver, lung, kidney, skin and thymus (at protein level). Expressed in granular layer of the cerebellum, forbrain, striatum, layer V of the cortex, olfactory cortex, tubercules, subthalamic and hippocampus, particularly in the CA2 region, to a lesser extent in the CA1 region and the external layer of the dentate gyrus. Expressed in neurons.|||Interacts with GNAI1 and GNAI2 (PubMed:15112653, PubMed:17635935). Interacts with GNAI3 (By similarity). Interacts with GNAO1 (PubMed:10926822). Interacts (via RGS and GoLoco domains) with GNAI1; the interaction occurs in the centrosomes. Interaction with GNAI1 or GNAI3 (via active GTP- or inactive GDP-bound forms) prevents association of RGS14 with centrosomes or nuclear localization (By similarity). Interacts with RABGEF1; the interactions is GTP-dependent (PubMed:10926822, PubMed:15112653). Interacts with RAP2A; the interactions is GTP-dependent and does not alter its function on G(i) alpha subunits either as GAP or as GDI (PubMed:10926822, PubMed:15112653). Associates with microtubules (By similarity). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIC8A (via C-terminus). Interacts (via RBD 1 domain) with HRAS (active GTP-bound form preferentially). Interacts (via RBD domains) with BRAF (via N-terminus); the interaction mediates the formation of a ternary complex with RAF1. Interacts (via RBD domains) with RAF1 (via N-terminus); the interaction mediates the formation of a ternary complex with BRAF. Interacts with KRAS (active GTP-bound form preferentially), MRAS (active GTP-bound form preferentially), NRAS (active GTP-bound form preferentially) and RRAS (active GTP-bound form preferentially) (By similarity).|||Membrane|||No visible phenotype. Mice show an enhancement of postsynaptic long-term potentiation (LTP) responses in the CA2 neurons of the hippocampus that is correlated with an increase of spatial learning and object recognition memory (OMR).|||Nucleus|||PML body|||Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1 (By similarity).|||Postsynaptic density|||Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o)-alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)-stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division; required for completion of the first mitotic division of the embryo. Involved in visual memory processing capacity; when overexpressed in the V2 secondary visual cortex area. Involved in hippocampal-based learning and memory; acts as a suppressor of synaptic plasticity in CA2 neurons. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance.|||The GoLoco domain is necessary for GDP-dissociation inhibitor (GDI) activity, translocation out of the nucleus and interaction with G(i) alpha subunits GNAI1, GNAI2 and GNAI3.|||The RBD domains are necessary for localization to the nucleus and centrosomes.|||The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes.|||centrosome|||dendrite|||dendritic spine|||spindle|||spindle pole http://togogenome.org/gene/10090:Alx1 ^@ http://purl.uniprot.org/uniprot/Q8C8B0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated at Lys-131 by EP300; increases interaction with EP300 and stimulates ALX1 transcriptional activity.|||At 8.5 dpc and 9.5 dpc expression is restricted to forebrain mesenchymal cells.|||Belongs to the paired homeobox family.|||Binds DNA as a homodimer; required for transcriptional activation (By similarity). Interacts (via homeobox domain) with EP300; acetylates ALX1 and stimulates its transcriptional activity (PubMed:12929931).|||Mice lacking Alx1 die within 24 hours of birth. The overt phenotype is acrania and degeneration of unprotected brain tissues. This is most probably the cause of the death since no other abnormality in limbs and visceral tissues is observed. The defect in cranial bone formation may be a consequence of extensive loss of forebrain head mesenchyme due to cell death and neural tube closure defects earlier during development. The penetrance of the acrania/meroanencephaly phenotype is variable between mice strains. Heterozygous mice appear normal and fertile.|||Nucleus|||Sequence-specific DNA-binding transcription factor that binds palindromic sequences within promoters and may activate or repress the transcription of a subset of genes (PubMed:12929931). Most probably regulates the expression of genes involved in the development of mesenchyme-derived craniofacial structures. Early on in development, it plays a role in forebrain mesenchyme survival (PubMed:8673125). May also induce epithelial to mesenchymal transition (EMT) through the expression of SNAI1 (By similarity).|||The OAR motif may negatively regulate DNA-binding and therefore transcriptional activity. It is found in the C-terminal transactivation domain that stimulates transcription. http://togogenome.org/gene/10090:Frem3 ^@ http://purl.uniprot.org/uniprot/F8WHZ0 ^@ Similarity ^@ Belongs to the FRAS1 family. http://togogenome.org/gene/10090:Fpgs ^@ http://purl.uniprot.org/uniprot/P48760 ^@ Activity Regulation|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A monovalent cation.|||Belongs to the folylpolyglutamate synthase family.|||Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Dihydrofolate, tetrahydrofolate, 5,10-methylenetetrahydrofolate, 10-formyltetrahydrofolate and 5-formyltetrahydrofolate are the best substrates. Folic acid and 5-methyltetrahydrofolate can also act as substrates.|||Cytoplasm|||Inhibited by ammonium sulfate. Inhibited by pentaglutamate derivative of DDATHF, but isoform 2 is inhibited to a greater extent at lower concentrations of the compound that is isoform 5. Isoform 5 is virtually unaffected by H(4)PteGlu(5) and 5,10-CH(2)-H(4)PteGlu(5) at concentrations that substantially inhibits the activity of isoform 2. Isoform 2 and 5 are equally sensitive to polyglutamates of 10-CHO-H(4)-PteGlu.|||Mitochondrion inner membrane|||Mitochondrion matrix|||Monomer.|||Produced by alternative initiation at Met-24 of isoform 4.|||Produced by alternative initiation at Met-43 of isoform 1.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||With non-specific probe, highest content in kidney and liver and lowest in spleen, lung and small intestine, and readily detectable in all of the tumors except hepatoma. Isoform 1 and isoform 2 expressed in leukemic cells and isoform 4 and isoform 5 in liver cells. Isoform 1 and isoform 2 exclusively expressed in hepatoma and Lewis lung carcinoma. Isoform 1 and isoform 2 also expressed in bone marrow, small intestine and spleen. Kidney expresses isoform 1, isoform 2, isoform 4 and isoform 5. http://togogenome.org/gene/10090:Tcl1b3 ^@ http://purl.uniprot.org/uniprot/P56842|||http://purl.uniprot.org/uniprot/Q0VBM6 ^@ Similarity ^@ Belongs to the TCL1 family. http://togogenome.org/gene/10090:Tcf19 ^@ http://purl.uniprot.org/uniprot/Q99KJ5 ^@ Miscellaneous|||Subcellular Location Annotation ^@ Nucleus|||This sequence is very similar to other orthologs but it lacks the PHD-type zinc finger domain which may be important for the trans-activation function. http://togogenome.org/gene/10090:Mapk12 ^@ http://purl.uniprot.org/uniprot/O08911 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-alpha.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Binds 2 magnesium ions.|||Cytoplasm|||Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3 and MAP2K6/MKK6, which activates the enzyme.|||Highly expressed in skeletal muscle. Also expressed in the heart, particularly in cardiac myocytes, lung, thymus and testes.|||Mitochondrion|||Monomer. Interacts with the PDZ domain of the syntrophin SNTA1 (By similarity). Interacts with SH3BP5, LIN7C, SCRIB and SYNJ2BP (By similarity). Interacts with PTPN4; this interaction induces the activation of PTPN4 phosphatase activity.|||Nucleus|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration.|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.|||Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway (By similarity). http://togogenome.org/gene/10090:Prss53 ^@ http://purl.uniprot.org/uniprot/Q571E5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||In vitro can degrade the fibrinogen alpha chain of as well as pro-urokinase-type plasminogen activator.|||Secreted http://togogenome.org/gene/10090:Vmn1r77 ^@ http://purl.uniprot.org/uniprot/E9PY60 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrpl19 ^@ http://purl.uniprot.org/uniprot/Q9D338 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL19 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ano7 ^@ http://purl.uniprot.org/uniprot/Q14AT5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Endoplasmic reticulum|||Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (PubMed:23532839). Does not exhibit calcium-activated chloride channel (CaCC) activity (PubMed:23532839). May play a role in cell-cell interactions (By similarity).|||Highly expressed in the stomach. Expressed at low levels in small intestine and large intestine.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Lama2 ^@ http://purl.uniprot.org/uniprot/Q5DTP0|||http://purl.uniprot.org/uniprot/Q60675 ^@ Caution|||Disease Annotation|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Defects in Lama2 are a cause of murine muscular dystrophy (dy2J).|||Domains VI, IV and G are globular.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-2 is a subunit of laminin-2 (laminin-211 or merosin), laminin-4 (laminin-221 or S-merosin) and laminin-12 (laminin-213). Interacts with FBLN1, FBLN2 and NID2.|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Or1e21 ^@ http://purl.uniprot.org/uniprot/Q8VGT3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dcaf12 ^@ http://purl.uniprot.org/uniprot/Q8BGZ3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat DCAF12 family.|||Component of the DCX(DCAF12) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF12 and RBX1.|||Cytoplasm|||Knockout mice are born at expected Mendelian ratios and manifest no apparent physical abnormalities. Mutants have testes that produce fewer mature sperms, an altered percentage of CD4(+) T-cells and natural killer (NK) cells as well as increased splenocyte apoptosis after T cell activation.|||Nucleus|||Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:34065512). The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading to their ubiquitination and degradation. Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12) complex is required for starvation-induced autophagy (By similarity). Also directly recognizes the C-terminal glutamate-leucine (Glu-Leu) degron as an alternative degron in proteins such as MOV10, leading to their ubiquitination and degradation. Controls the protein level of MOV10 during spermatogenesis and in T cells, especially after their activation (PubMed:34065512).|||centrosome http://togogenome.org/gene/10090:Ogfod1 ^@ http://purl.uniprot.org/uniprot/Q3U0K8 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TPA1 family.|||Binds 1 Fe(2+) ion per subunit.|||Contains Thr-228 instead of the expected predicted active site Lys.|||Cytoplasm|||Monomer.|||Nucleus|||Prolyl 3-hydroxylase that catalyzes 3-hydroxylation of 'Pro-62' of small ribosomal subunit uS12 (RPS23), thereby regulating protein translation termination efficiency. Involved in stress granule formation. http://togogenome.org/gene/10090:Lhx4 ^@ http://purl.uniprot.org/uniprot/P53776 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ May play a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung. Binds preferentially to methylated DNA (By similarity).|||Nucleus|||Transient expression in ventrolateral regions of the developing neural tube and hindbrain. http://togogenome.org/gene/10090:Flrt1 ^@ http://purl.uniprot.org/uniprot/Q6RKD8 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Cell membrane|||Cytoplasmic vesicle membrane|||Detected at comparable levels in embryonic brain and in brain from ten day old animals (at protein level) (PubMed:16872596). Detected in neuroectoderm at 7.5 dpc. Detected in midbrain between 8.5 and 9 dpc (PubMed:18448090). Detected at 9.5 dpc in embryonic midbrain adjacent to the boundary between midbrain and forebrain (PubMed:16872596). At 10.5 dpc, expression is also detected in the eye, throughout the brain, the dorsal root ganglia and trigeminal ganglia, and in cells adjacent to the urogenital ridge in the torso (PubMed:16872596, PubMed:18448090). At 11 dpc, expression in midbrain is tightly restricted to the boundary between midbrain and hindbrain (PubMed:16872596).|||Detected in brain (at protein level).|||Endoplasmic reticulum membrane|||Interacts with FGFR1 (PubMed:16872596). Interacts (via extracellular domain) with ADGRL1/LPHN1 and ADGRL3 (via olfactomedin-like domain) (PubMed:22405201).|||N-glycosylated.|||Phosphorylated in response to FGFR1 signaling, but is not a direct substrate of FGFR1 or SRC. A mutant where the Tyr phosphorylation sites have been replaced by Phe displays constitutive FGFR1-dependent activation of downstream MAP kinases.|||Plays a role in fibroblast growth factor-mediated signaling cascades that lead to the activation of MAP kinases (PubMed:16872596, PubMed:20421966). Promotes neurite outgrowth via FGFR1-mediated activation of downstream MAP kinases. Promotes an increase both in neurite number and in neurite length (PubMed:20421966). May play a role in cell-cell adhesion and cell guidance via its interaction with ADGRL1/LPHN1 and ADGRL3 (PubMed:22405201).|||Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain.|||Secreted|||Up-regulated by FGF2.|||focal adhesion|||neuron projection|||perinuclear region http://togogenome.org/gene/10090:Ei24 ^@ http://purl.uniprot.org/uniprot/Q61070 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative growth regulator via p53-mediated apoptosis pathway. Regulates formation of degradative autolysosomes during autophagy (By similarity).|||Belongs to the EI24 family.|||By etoposide treatment, induction requires p53. Etoposide induces DNA damage in cells by inhibiting DNA topoisomerase II, and ultimately causes apoptotic cell death.|||Cytoplasm|||Endoplasmic reticulum membrane|||Found in all the examined tissues. High expression was found in liver, skeletal muscle, pancreas, kidney heart and to a lesser extent in brain, placenta and lung.|||Interacts with BCL2.|||Nucleus membrane http://togogenome.org/gene/10090:Lrrc49 ^@ http://purl.uniprot.org/uniprot/Q91YK0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1 (PubMed:15890843). Interacts with PCM1; TTLL1, TPGS1, TPGS2 and LRRC49 (By similarity).|||Subunit of the tubulin polyglutamylase complex (TPGC). The complex mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility.|||centriolar satellite|||cytoskeleton http://togogenome.org/gene/10090:Pgam5 ^@ http://purl.uniprot.org/uniprot/Q8BX10 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.|||Dimer. Forms a ternary complex with NFE2L2 and KEAP1. Interacts with BCL2L1 and MAP3K5 (By similarity). Upon TNF-induced necrosis, forms in complex with RIPK1, RIPK3 and MLKL; the formation of this complex leads to PGAM5 phosphorylation (By similarity). Interacts with DNM1L; this interaction leads to DNM1L dephosphorylation and activation and eventually to mitochondria fragmentation (By similarity).|||Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression (By similarity). Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Phosphorylated by the RIPK1/RIPK3 complex under necrotic conditions. This phosphorylation increases PGAM5 phosphatase activity (By similarity).|||Proteolytically cleaved by PARL in response to loss of mitochondrial membrane potential.|||The N-terminal 35 amino acids, including the potential transmembrane alpha-helix, function as a non-cleaved mitochondrial targeting sequence that targets the protein to the cytosolic side of the outer mitochondrial membrane. http://togogenome.org/gene/10090:Bmp15 ^@ http://purl.uniprot.org/uniprot/Q9Z0L4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Homodimer (By similarity). But, in contrast to other members of this family, cannot be disulfide-linked.|||May be involved in follicular development. Oocyte-specific growth/differentiation factor that stimulates folliculogenesis and granulosa cell (GC) growth (By similarity).|||Ovary specific.|||Secreted http://togogenome.org/gene/10090:Ago1 ^@ http://purl.uniprot.org/uniprot/A0A6I8MX18|||http://purl.uniprot.org/uniprot/Q8BJP2|||http://purl.uniprot.org/uniprot/Q8CJG1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the argonaute family.|||Belongs to the argonaute family. Ago subfamily.|||Interacts with DDB1, DDX5, DDX6, DHX30, DHX36, DDX47, DICER1, AGO2, ELAVL1, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, RBM4, SART3, TNRC6B, UPF1 and YBX1. Associates with polysomes and messenger ribonucleoproteins (mNRPs) (By similarity). Interacts with LIMD1, WTIP and AJUBA (By similarity). Interacts with APOBEC3F, APOBEC3G and APOBEC3H (By similarity).|||P-body|||Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. May also be required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).|||Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO1 when it is engaged with a TDMD target. http://togogenome.org/gene/10090:Mical2 ^@ http://purl.uniprot.org/uniprot/Q8BML1 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mical family.|||Cytoplasm|||During spermatogenesis, first expressed after meiosis, gradually increases to a maximum at Oakberg's stage 9 and then decreases until it is undetectable when spermatozoa begin to generate flagella (at protein level).|||Expressed only in testis (at protein level).|||Interacts with PLXNA4 (PubMed:12110185). Interacts with RAB1B (By similarity). Interacts with MAPK1/ERK2 (PubMed:18241670, PubMed:18590835). Interacts with RAB1B, RAB35, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B and RAB35 is of low affinity compared to other Rab proteins; binding to RAB1B and RAB35 is of low affinity compared to other Rab proteins; at least in case of RAB8A may bind 2 molecules of RAB8A simultaneously through a high and a low affinity binding site, respectively (By similarity).|||Methionine monooxygenase that promotes depolymerization of F-actin by mediating oxidation of residues 'Met-44' and 'Met-47' on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (PubMed:23911929, PubMed:23927065). Regulates the disassembly of branched actin networks also by oxidizing ARP3B-containing ARP2/3 complexes leading to ARP3B dissociation from the network. Acts as a key regulator of the SRF signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A through RhoA (By similarity).|||Nucleus|||The C-terminal RAB-binding domain (RBD)(1796-1945), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms). http://togogenome.org/gene/10090:Spata6l ^@ http://purl.uniprot.org/uniprot/B2RV46|||http://purl.uniprot.org/uniprot/Q8BI12 ^@ Similarity ^@ Belongs to the SPATA6 family. http://togogenome.org/gene/10090:Meox2 ^@ http://purl.uniprot.org/uniprot/P32443 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with RNF10 (By similarity). Interacts with TCF15 (PubMed:25561514).|||It is not expressed before 8-8.5 dpc (PubMed:1363541). At 8-8.5 dpc it is found on the entire epithelium of the somite (PubMed:1363541). At 9.5 dpc its expression is restricted to the sclerotome (PubMed:1363541). At 10.5 dpc it is found in sclerotomally derived cells including the vertebral and costal precursors (PubMed:1363541).|||Mesodermal transcription factor that plays a key role in somitogenesis and somitogenesis and limb muscle differentiation (PubMed:12925591, PubMed:10403250, PubMed:1363541). Required during limb development for normal appendicular muscle formation and for the normal regulation of myogenic genes (PubMed:10403250). May have a regulatory role when quiescent vascular smooth muscle cells reenter the cell cycle (By similarity). Also acts as a negative regulator of angiogenesis (PubMed:16116430). Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation (By similarity). While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner (By similarity). Together with TCF15, regulates transcription in heart endothelial cells to regulate fatty acid transport across heart endothelial cells (PubMed:25561514).|||Mice display defective differentiation and morphogenesis of the limb muscles, characterized by an overall reduction in muscle mass and elimination of specific muscles (PubMed:10403250, PubMed:12925591). Embryos also display a cleft palate phenotype at 15.5 dpc (PubMed:16284941). Mice lacking Meox1 and Meox2 show extremely disrupted somite morphogenesis, patterning and differentiation (PubMed:12925591). They lack an axial skeleton and skeletal muscles are severely deficient (PubMed:12925591).|||Nucleus|||Nucleus speckle|||The polyhistidine repeat may act as a targeting signal to nuclear speckles. http://togogenome.org/gene/10090:Cyp2c66 ^@ http://purl.uniprot.org/uniprot/Q5GLZ0 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Dcdc2a ^@ http://purl.uniprot.org/uniprot/Q5DU00 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals develop periportal hepatic fibrosis with biliary duct proliferation at age 11 months.|||Expressed in hair cells of the inner ear.|||Interacts with DVL1, DVL2 and DVL3.|||Protein that plays a role in the inhibition of canonical Wnt signaling pathway (By similarity). May be involved in neuronal migration during development of the cerebral neocortex (By similarity). Involved in the control of ciliogenesis and ciliary length (By similarity).|||cilium|||cilium axoneme|||cytoskeleton|||kinocilium http://togogenome.org/gene/10090:St13 ^@ http://purl.uniprot.org/uniprot/Q99L47 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM10 family.|||Cytoplasm|||Homotetramer. Interacts with HSC70 as well as DNAJ homologs and HSP90 (By similarity). Interacts (via the C-terminus 302- 318 AA) with GRK5 (By similarity).|||One HIP oligomer binds the ATPase domains of at least two HSC70 molecules dependent on activation of the HSC70 ATPase by HSP40. Stabilizes the ADP state of HSC70 that has a high affinity for substrate protein. Through its own chaperone activity, it may contribute to the interaction of HSC70 with various target proteins (By similarity). http://togogenome.org/gene/10090:Aldh1a3 ^@ http://purl.uniprot.org/uniprot/Q3UIA4|||http://purl.uniprot.org/uniprot/Q9JHW9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively (PubMed:11013254, PubMed:11044606, PubMed:14623956, PubMed:15911617). High specificity for all-trans-retinal as substrate, can also accept acetaldehyde as substrate in vitro but with lower affinity (By similarity). Required for the biosynthesis of normal levels of retinoate in the embryonic ocular and nasal regions; a critical lipid in the embryonic development of the eye and the nasal region (PubMed:14623956).|||Cytoplasm|||Detected in embryonic head (at protein level) (PubMed:14623956). Ventral retina.|||Homotetramer.|||In mouse embryos, RALDH3 expression is first noticed in the ventral optic eminence at 8.75 dpc, then in the optic vesicle/cup, otic vesicle and olfactory placode/pit from 9.5 dpc to 11.5 dpc.|||Mutant mice are born at the expected Mendelian rate, but all die within 10 hours after birth (PubMed:14623956, PubMed:23536097). Lethality is due to respiratory distress, caused by choanal atresia, i.e. the lack of communication between the nasal and oral cavities. Mutant embryos at 11.5 dpc lack detectable retinoic acid in the ventral retina, nasal epithelium and in the nasolacrimal groove. At 14.5 dpc mutant embryos display shortening of the ventral retina associated with lens rotation and persistence of the retrolenticular membrane, indicative of retinoic acid deficiency. Still, at 18.5 dpc the ventral retina appears normal. Embryos at 18.5 dpc lack Harderian glands, and display multiple malformations in the nasal region, including choanal atresia, lack of maxillary sinuses and nasolacrimal ducts (PubMed:14623956). Oral gavage of pregnant females with retinoic acid prevents choanal atresia and other malformations of the nasal region (PubMed:14623956, PubMed:23536097). Females that were fed retinoic acid give birth to pups with malformations of the inner ear vestibular organ, causing repetitive circling behavior with head tilting (PubMed:23536097). Likewise, mice display impaired ability in crossing a beam without slipping and an impaired ability to swim (PubMed:23536097). http://togogenome.org/gene/10090:Elmod1 ^@ http://purl.uniprot.org/uniprot/Q3V1U8 ^@ Function ^@ Acts as a GTPase-activating protein (GAP) toward guanine nucleotide exchange factors like ARL2, ARL3, ARF1 and ARF6, but not for GTPases outside the Arf family. http://togogenome.org/gene/10090:Gpr17 ^@ http://purl.uniprot.org/uniprot/Q6NS65 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Dual specificity receptor for uracil nucleotides and cysteinyl leukotrienes (CysLTs). Signals through G(i) and inhibition of adenylyl cyclase. May mediate brain damage by nucleotides and CysLTs following ischemia (By similarity). http://togogenome.org/gene/10090:Kif1c ^@ http://purl.uniprot.org/uniprot/O35071|||http://purl.uniprot.org/uniprot/Q3V3Y9|||http://purl.uniprot.org/uniprot/Q8VI89 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Unc-104 subfamily.|||Monomer.|||Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum. Has a microtubule plus end-directed motility (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Eif1ad19 ^@ http://purl.uniprot.org/uniprot/F6YNI8 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Usp37 ^@ http://purl.uniprot.org/uniprot/A0A0R4J2D0|||http://purl.uniprot.org/uniprot/Q8C0R0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Chromosome|||Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response. Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1. Plays also an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability. Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM. Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM. Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI. Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Interacts with FZR1/CDH1. Interacts with CDT1.|||Nucleus|||Phosphorylated at Ser-628 by CDK2 during G1/S phase but not during mitosis; phosphorylation at Ser-628 is required for deubiquitinase activity. Also polyubiquitinated during early G1 phase, without leading to degradation. Phosphorylated at Ser-114 by ATM following DNA damage, which in turn increases its deubiquitination activity towards BLM.|||Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination.|||The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination. http://togogenome.org/gene/10090:Ugt2b37 ^@ http://purl.uniprot.org/uniprot/Q8VCN3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Slc7a11 ^@ http://purl.uniprot.org/uniprot/Q542C8|||http://purl.uniprot.org/uniprot/Q9WTR6 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.|||Cell membrane|||Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc; this interaction mediates cell membrane localization.|||Expressed in cornea, lens, and retina (at protein level), namely in the corneal epithelium, lens epithelium and cortical fiber cells.|||Heterodimer with SLC3A2, that functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:10206947, PubMed:12235164, PubMed:16144837, PubMed:16037214, PubMed:17035536) (Probable). Provides L-cystine for the maintenance of the redox balance between extracellular L-cystine and L-cysteine and for the maintenance of the intracellular levels of glutathione that is essential for protection of cells from oxidative stress (PubMed:31396687, PubMed:16144837, PubMed:16037214, PubMed:17035536). The transport is sodium-independent, electroneutral with a stoichiometry of 1:1, and is drove by the high intracellular concentration of L-glutamate and the intracellular reduction of L-cystine (PubMed:10206947). In addition, mediates the import of L-kynurenine leading to anti-ferroptotic signaling propagation required to maintain L-cystine and glutathione homeostasis (By similarity). Moreover, mediates N-acetyl-L-cysteine uptake into the placenta leading to subsequently down-regulation of pathways associated with oxidative stress, inflammation and apoptosis (By similarity). In vitro can also transport L-aspartate (By similarity). May participate in astrocyte and meningeal cell proliferation during development and can provide neuroprotection by promoting glutathione synthesis and delivery from non-neuronal cells such as astrocytes and meningeal cells to immature neurons (PubMed:17035536). Controls the production of pheomelanin pigment directly (PubMed:16037214).|||Homozygous mice lacking SLC7A11 are healthy in appearance at the age of 6 months, develop normally and both males and females are fertile (PubMed:16144837). Mice contain approximately the double of plasma L-cystine concentration and approximately the half of glutathione concentration compare to the wild-type mice (PubMed:16144837). Subtle gray (sut) homozygous mice have reduced yellow hair pigment but the black pigment seems unaffected (PubMed:16037214). Sut mice exhibit a normal body weight but brain size is significantly reduced indicating an atrophy in certain brain tissues. Indeed, sut/sut mice exhibit pronounced enlargement of the ventricles, accompanied by thinning of the cortex and shrinkage of the striatum (PubMed:17035536).|||Induced by diethyl maleate (PubMed:12235164). Up-regulated by lipopolysaccharide (LPS) and oxygen (PubMed:11136724).|||Membrane|||Ubiquitinated by TRIM26; leading to proteasomal degradation.|||microvillus membrane http://togogenome.org/gene/10090:Snupn ^@ http://purl.uniprot.org/uniprot/Q80W37 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snurportin family.|||Component of an import snRNP complex composed of KPNB1, SNUPN, SMN1 and ZNF259. Component of a nuclear export receptor complex composed of KPNB1, Ran, SNUPN and XPO1. Found in a trimeric export complex with SNUPN, Ran and XPO1. Interacts (via IBB domain) with KPNB1; the interaction is direct. Interacts with DDX20, IPO7, SMN1, SNRPB and XPO1. Interacts directly with XPO1. Its interaction with XPO1 and binding to m3G-cap U snRNPs appears to be mutually exclusive.|||Cytoplasm|||Functions as an U snRNP-specific nuclear import adapter. Involved in the trimethylguanosine (m3G)-cap-dependent nuclear import of U snRNPs. Binds specifically to the terminal m3G-cap U snRNAs.|||Nucleus http://togogenome.org/gene/10090:Macir ^@ http://purl.uniprot.org/uniprot/Q8VEB3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UNC119-binding protein family.|||Cytoplasm|||Highly expressed in photoreceptors.|||Interacts with UNC119 and UNC119B; interaction preferentially takes place when UNC119 and UNC119B are unliganded with myristoylated proteins.|||Regulates the macrophage function, by enhancing the resolution of inflammation and wound repair functions mediated by M2 macrophages. The regulation of macrophage function is, due at least in part, to its ability to inhibit glycolysis. May also play a role in trafficking of proteins via its interaction with UNC119 and UNC119B cargo adapters: may help the release of UNC119 and UNC119B cargo or the recycling of UNC119 and UNC119B. May play a role in ciliary membrane localization via its interaction with UNC119B and protein transport into photoreceptor cells.|||cilium http://togogenome.org/gene/10090:Ddx59 ^@ http://purl.uniprot.org/uniprot/Q9DBN9 ^@ Developmental Stage|||Domain|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AT 11.5 dpc, expressed in the developing snout region, eye and limb buds. At 13.5 dpc, highly enriched in the lips, palatal shelves (secondary palate), and developing limb buds.|||Belongs to the DEAD box helicase family. DDX59 subfamily.|||Cytoplasm|||Interacts (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the presence of ADP.|||Nucleus|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis. http://togogenome.org/gene/10090:Tsks ^@ http://purl.uniprot.org/uniprot/O54887 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ May play a role in testicular physiology, most probably in the process of spermatogenesis or spermatid development.|||Phosphorylated on serine residue(s) by STK22A/TSSK1 and STK22B/TSSK2.|||Testis specific.|||acrosome|||centriole http://togogenome.org/gene/10090:Or8k41 ^@ http://purl.uniprot.org/uniprot/A0A1L1SR98 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hsd17b12 ^@ http://purl.uniprot.org/uniprot/O70503|||http://purl.uniprot.org/uniprot/Q0VGQ1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.|||Catalyzes the second of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation.|||Endoplasmic reticulum membrane|||Expressed in most tissues tested.|||The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins. http://togogenome.org/gene/10090:Ntpcr ^@ http://purl.uniprot.org/uniprot/Q9CQA9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the THEP1 NTPase family.|||Has nucleotide phosphatase activity towards ATP, GTP, CTP, TTP and UTP. Hydrolyzes nucleoside diphosphates with lower efficiency.|||Monomer. http://togogenome.org/gene/10090:Htr1a ^@ http://purl.uniprot.org/uniprot/Q64264 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. 5-hydroxytryptamine receptor subfamily. HTR1A sub-subfamily.|||Cell membrane|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.|||Heterodimer; heterodimerizes with GPER1 (By similarity). Interacts with YIF1B (By similarity).|||Most abundantly expressed in midbrain, in dorsal raphe and hippocampus. Detected at lower levels in amygdala and brain cortex.|||Mutant mice display decreased exploratory behavior and increased fear-related behavior in anxiogenic environments. Mutant mice display altered monoamine metabolism in specific parts of the brain, especially in dorsal and medial raphe nuclei, thalamus and hypothalamus, leading to altered levels of 5-hydroxytryptamine, dopamine and their metabolites, as well as altered noradrenaline levels.|||dendrite http://togogenome.org/gene/10090:Ms4a7 ^@ http://purl.uniprot.org/uniprot/E9Q9V5|||http://purl.uniprot.org/uniprot/Q3UAR5|||http://purl.uniprot.org/uniprot/Q8BV59|||http://purl.uniprot.org/uniprot/Q99N04|||http://purl.uniprot.org/uniprot/Q9D2W6 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Bcam ^@ http://purl.uniprot.org/uniprot/Q9R069 ^@ Function|||Subcellular Location Annotation ^@ Laminin alpha-5 receptor. May mediate intracellular signaling (By similarity).|||Membrane http://togogenome.org/gene/10090:Dlg5 ^@ http://purl.uniprot.org/uniprot/E9Q9R9|||http://purl.uniprot.org/uniprot/Q6NXJ3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a regulator of the Hippo signaling pathway. Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial-mesenchymal transition (EMT), cell migration and invasion (By similarity). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N-cadherin (PubMed:25232112). Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (PubMed:25644602).|||Belongs to the MAGUK family.|||Belongs to the SHANK family.|||Brain (at protein level).|||Cell junction|||Cell membrane|||Cytoplasm|||Interacts with MPP1. Interacts with CTNNB1 and with the third SH3 domain of SORBS3 to form a ternary complex (By similarity). Interacts (via coiled-coil domain) with MARK3. Interacts (via PDZ domain 3) with STK3/MST2 and STK4/MST1 (PubMed:28087714). Interacts with SCRIB (By similarity). Interacts with CTNB1 (PubMed:25232112). Interacts with SMO and (via PDZ4 or guanylate kinase-like domain) with KIF7 (PubMed:25644602).|||Postsynaptic density|||The guanylate kinase-like domain interacts with the SH3 domain.|||cilium basal body http://togogenome.org/gene/10090:Ctsa ^@ http://purl.uniprot.org/uniprot/G3X8T3|||http://purl.uniprot.org/uniprot/P16675|||http://purl.uniprot.org/uniprot/Q544R6|||http://purl.uniprot.org/uniprot/Q9D2D1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S10 family.|||Heterodimer of a 32 kDa chain and a 20 kDa chain; disulfide-linked.|||Lysosome|||Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins. http://togogenome.org/gene/10090:Vwa2 ^@ http://purl.uniprot.org/uniprot/Q70UZ7|||http://purl.uniprot.org/uniprot/Q8CE01 ^@ Caution|||Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in uterus, kidney, and skin. Also detected in intestine and lung of adult mice, and in calvaria, femur, brain, heart, intestine, skeletal muscle, and lung of newborn mice.|||First detected at days 7.5-8 dpc, when it is weakly expressed around the developing mesodermal cells. At day 10.5 dpc it is detected in the heart and the condensing somites, and at day 14.5 dpc it is present in the choroid plexus, the cochlea, the terminal bronchii of the lung, the heart, the skin, and in the cartilage primordium of the developing skeleton as well as in the interdigital spaces. Strong staining is seen in the condensed mesenchyme forming the edge of the developing teeth budding into the branchial arch and coinciding with the basement membrane that underlies the stratified squamous epithelia in the oral cavity.|||Forms monomers and multimers.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Nsmf ^@ http://purl.uniprot.org/uniprot/Q99NF2 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc embryo found at high levels within the forebrain, olfactory epithelium and olfactory pit. At 12.5 dpc embryo detected on olfactory axons including olfactory pathway on which the LHRH neurons move. From 11.5 dpc to 17.5 dpc embryos expressed in LHRH (luteinizing hormone-releasing hormone) neurons as they migrate from the olfactory pit into the developing forebrain.|||Belongs to the NSMF family.|||Cell membrane|||Couples NMDA-sensitive glutamate receptor signaling to the nucleus and triggers long-lasting changes in the cytoarchitecture of dendrites and spine synapse processes. Part of the cAMP response element-binding protein (CREB) shut-off signaling pathway. Stimulates outgrowth of olfactory axons and migration of gonadotropin-releasing hormone (GnRH) and luteinizing-hormone-releasing hormone (LHRH) neuronal cells.|||Cytoplasm|||Interacts with KPNA1; the interaction occurs in a calcium-independent manner after synaptic NMDA receptor stimulation and is required for nuclear import of NSMF but is competed by CABP1. Interacts (via the central NLS-containing motif region) with CABP1 (via EF-hands 1 and 2); the interaction occurs in a calcium-dependent manner after synaptic NMDA receptor stimulation and prevents the nuclear import of NSMF. Cannot be competed by calmodulin (By similarity).|||Membrane|||Nucleus|||Nucleus envelope|||Nucleus matrix|||Nucleus membrane|||Postsynaptic density|||Preferentially expressed in immature migratory, in comparison to postmigrating, gonadotropin-releasing hormone (GnRH) neuronal cell lines (at protein level). Expressed in adult brain and liver. In the brain, expressed in the primary pituitary gland, cortex, hippocampus, olfactory bulb and thalamus.|||Proteolytically processed after NMDA receptor activation. Cleaved in a calcium-dependent and calpain-sensitive manner. Calpain cleavage is essential for the translocation process from dendrites to the nucleus (By similarity).|||Synapse|||Transport from dendrites to the nucleus is induced by NMDA receptor activation and results in a rapid stripping of synaptic contacts and a reduction of dendritic complexity (By similarity). KIF5C associates to its 3'-UTR mRNA in granules along dendritic shafts, suggesting that this protein may regulate its dendritic trafficking and local translation at postsynaptic sites.|||Up-regulated by gonadotropin releasing hormone (GnRH).|||cell cortex|||cytoskeleton|||dendrite|||synaptosome http://togogenome.org/gene/10090:Pcdha3 ^@ http://purl.uniprot.org/uniprot/Q91Y16 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Unc13a ^@ http://purl.uniprot.org/uniprot/H3BJZ7|||http://purl.uniprot.org/uniprot/Q4KUS2 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts with the N-termini of STX1A and/or STX1B1 and DOC2A. Interacts with BSN. Interacts with RIMS1 which recruits UNC13A to the active zone. Forms homodimers via its first C2 domain. Also interacts via this domain with the zinc finger domain of RIMS2. Part of a complex consisting of ERC2, RIMS1 and UNC13A. Also part of a complex consisting of UNC13A, RIMS2 and RAB3A (By similarity). Interacts with FBXO45 (via SRY domain); leading to the degradation of UNC13A by the proteasome (PubMed:19996097).|||Membrane|||Mice display normal synapse formation but abnormal synaptic vesicle maturation and die shortly after birth. Heterozygotes exhibit impaired insulin secretion and abnormal glucose tolerance.|||Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896). Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (By similarity).|||Presynaptic active zone|||Presynaptic cell membrane|||The C-terminal region containing both MHD domains and the third C2 domain is required for synaptic vesicle priming activity.|||The C2 domains are not involved in calcium-dependent phospholipid binding. http://togogenome.org/gene/10090:Taar7b ^@ http://purl.uniprot.org/uniprot/Q5QD11 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Herc6 ^@ http://purl.uniprot.org/uniprot/F2Z461 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation ^@ Abolishes global ISGylation.|||By type I interferons.|||Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon.|||cytosol http://togogenome.org/gene/10090:Ube3c ^@ http://purl.uniprot.org/uniprot/Q80U95 ^@ Function|||PTM|||Similarity|||Subunit ^@ Autoubiquitinated; promoting its own degradation.|||Belongs to the UBE3C family.|||E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-29'- and 'Lys-48'-linked polyubiquitin chains (By similarity). Accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (By similarity). Associates with the proteasome and promotes elongation of ubiquitin chains on substrates bound to the 26S proteasome (By similarity). Also catalyzes 'Lys-29'- and 'Lys-48'-linked ubiquitination of 26S proteasome subunit ADRM1/RPN13 in response to proteotoxic stress, impairing the ability of the proteasome to bind and degrade ubiquitin-conjugated proteins (By similarity). Acts as a negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-linked ubiquitination of PIK3C3/VPS34, promoting its degradation (By similarity). Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some preference for 'Lys-48' linkages (By similarity). Acts as a negative regulator of type I interferon by mediating 'Lys-48'-linked ubiquitination of IRF3 and IRF7, leading to their degradation by the proteasome (PubMed:21167755). Catalyzes ubiquitination and degradation of CAND2 (By similarity).|||Interacts with 26S proteasomes. Interacts (via the HECT domain) with UBE2D1 and, less efficiently, with UBE2L3. http://togogenome.org/gene/10090:Wdr41 ^@ http://purl.uniprot.org/uniprot/Q3UDP0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41. The complex is formed of two protomers, each individually consisting of one molecule each of C9orf72, SMCR8 and WDR41 (By similarity). The protomers homodimerize via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-terminus) (By similarity). Within each protomer SMCR8 (via DENN domain) acts as a bridging protein between WDR41 (via C-terminus and N-terminus) and C9orf72 (via C-terminus) (By similarity). The C9orf72-SMCR8 complex associates with the ULK1/ATG1 kinase complex.|||Cytoplasm|||Non-catalytic component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. The C9orf72-SMCR8 complex promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation. As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro, however WDR42 is shown not be an essential complex component for this function (By similarity). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity. http://togogenome.org/gene/10090:1190005I06Rik ^@ http://purl.uniprot.org/uniprot/Q8K1L6 ^@ Subunit ^@ Interacts (via PxIxIT motif, when phosphorylated on Thr-79) with PPP3CA. http://togogenome.org/gene/10090:Rac1 ^@ http://purl.uniprot.org/uniprot/P63001 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Conditional knockout of Rac1 in the telencephalic ventricular zone of embryos leads to primary microcephaly. Self-renewal, survival, and differentiation of telencephalic neural progenitor cells is affected.|||Cytoplasm|||Expressed in the neocortical neurons in the developing brain.|||GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome.|||Interacts with the GEF proteins PREX1, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with BAIAP2, BAIAP2L1, PLXNB1, CYFIP1/SRA-1 and DEF6. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ITGB4. Interacts with the GTP-bound form of RAB7A. Interacts with ARHGEF2. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with NOXA1. Interacts with S100A8 and calprotectin (S100A8/9). Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts with PACSIN2. Interacts with ITGB1BP1 (By similarity). Interacts with the GEF protein RASGRF2, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a complex with MAP2K3, MAP3K3 and CCM2. Interacts with NISCH. Interacts with PIP5K1A. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with SRGAP2. Interacts with PLXNB3. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RAPH1 (via Ras associating and PH domains) (By similarity). Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation. Interacts (GTP-bound form) with SH3RF3. Interacts with PAK2 (By similarity). Interacts (GTP-bound form) with SH3RF1 (PubMed:22959435). Found in a complex with SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1 (PubMed:23963642). Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2 (By similarity). Interacts (GTP-bound form preferentially) with CYRIB (By similarity). Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (By similarity). Interacts with GARRE1 (By similarity). Interacts with RAP1GDS1 (By similarity). Interacts with TNFAIP8L2 (By similarity).|||Melanosome|||Nucleus|||Phosphorylated by AKT at Ser-71.|||Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states (PubMed:24352656). In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. In neurons, is involved in dendritic spine formation and synaptic plasticity (PubMed:24352656, PubMed:26969129). In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity).|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44.|||Synapse|||The effector region mediates interaction with DEF6.|||Ubiquitinated at Lys-166 in a FBXL19-mediated manner; leading to proteasomal degradation.|||Widely expressed.|||dendrite|||lamellipodium http://togogenome.org/gene/10090:Togaram2 ^@ http://purl.uniprot.org/uniprot/Q3TYG6 ^@ Similarity ^@ Belongs to the Crescerin family. http://togogenome.org/gene/10090:Havcr1 ^@ http://purl.uniprot.org/uniprot/Q5QNS5 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.|||Belongs to the immunoglobulin superfamily. TIM family.|||Cell membrane|||Expressed by stimulated T-cells. Expressed during primary antigen stimulation (PubMed:11725301). Expressed at higher levels on B rather than T-cells, both constitutively and after activation (PubMed:21821911).|||Highly polymorphic. Depending on the alleles, expression is associated with an increase and early (BALB/c allele) or decrease (HBA allele) of T-helper type 2 cytokine expression. Associated with asthma susceptibility.|||Interacts with STAM (By similarity). Interacts with SELPLG (PubMed:24703780).|||Mutant show progressive loss of IL10 production in B-cells and with age develop severe multiorgan tissue inflammation (PubMed:25582854). Mucin-domain deletion mice exhibit decreased phosphatidylserine binding and are also unable to produce IL10 in response to apoptotic cells (PubMed:25645598). Specific deletion on B-cells results in spontaneous systemic autoimmunity (PubMed:32668241).|||Phosphatidylserine receptor that plays an important functional role in regulatory B-cells homeostasis including generation, expansion and suppressor functions (PubMed:21821911, PubMed:25645598, PubMed:32668241). As P-selectin/SELPLG ligand, plays a specialized role in activated but not naive T-cell trafficking during inflammatory responses (PubMed:24703780). Controls thereby T-cell accumulation in the inflamed central nervous system (CNS) and the induction of autoimmune disease (PubMed:24703780). Regulates also expression of various anti-inflammatory cytokines and co-inhibitory ligands including IL10 (PubMed:25582854, PubMed:25645598). Acts as regulator of T-cell proliferation (PubMed:15793576). May play a role in kidney injury and repair (By similarity).|||Possesses an immunoglobulin V-like domxain, a mucin domain, a single transmembrane region, and a cytoplasmic tail containing a tyrosine phosphorylation motif. http://togogenome.org/gene/10090:Mars1 ^@ http://purl.uniprot.org/uniprot/E9QB02|||http://purl.uniprot.org/uniprot/Q68FL6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. Plays a role in the synthesis of ribosomal RNA in the nucleolus.|||Monomer. Part of a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18. Forms a linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit complex.|||cytosol|||nucleolus http://togogenome.org/gene/10090:Lipt2 ^@ http://purl.uniprot.org/uniprot/Q9D009 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LipB family.|||Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-dependent enzymes, which catalyze essential redox reactions (By similarity). Lipoyl-ACP can also act as a substrate although octanoyl-ACP is likely to be the physiological substrate (By similarity).|||In the reaction, the free carboxyl group of octanoic acid is attached via an amide linkage to the epsilon-amino group of a specific lysine residue of lipoyl domains of lipoate-dependent enzymes.|||Mitochondrion http://togogenome.org/gene/10090:H1f8 ^@ http://purl.uniprot.org/uniprot/Q8VIK3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the histone H1/H5 family.|||Chromosome|||Cytoplasm|||Expressed as early as the germinal vesicle (GV) stage oocyte, and persists into the metaphase II stage oocyte, the oocytic polar bodies, and the 2-cell embryo, and disappears at the 4- to 8-cell embryonic stage.|||May play a key role in the control of gene expression during oogenesis and early embryogenesis, presumably through the perturbation of chromatin structure. Essential for meiotic maturation of germinal vesicle-stage oocytes. The somatic type linker histone H1c is rapidly replaced by H1oo in a donor nucleus transplanted into an oocyte. The greater mobility of H1oo as compared to H1c may contribute to this rapid replacement and increased instability of the embryonic chromatin structure. The rapid replacement of H1c with H1oo may play an important role in nuclear remodeling.|||Nucleus|||Oocyte-specific. http://togogenome.org/gene/10090:Selenos ^@ http://purl.uniprot.org/uniprot/Q9BCZ4 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the selenoprotein S family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Interacts with DERL1 and (via VIM motif) with VCP, suggesting that it forms a membrane complex with DERL1 that serves as a receptor for VCP. Also interacts with DERL2, DERL3 and SELENOK. The SELENOK-SELENOS complex interacts with VCP (By similarity). Interacts with CCDC47 (PubMed:25009997).|||Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Probably acts by serving as a linker between DERL1, which mediates the retrotranslocation of misfolded proteins into the cytosol, and the ATPase complex VCP, which mediates the translocation and ubiquitination (By similarity).|||One of the histocompatibility antigen responsible for chronic graft rejection.|||Truncated SELENOS proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(KLHDC2) and CRL2(KLHDC3) complexes, which recognizes the glycine (Gly) at the C-terminus of truncated SELENOS proteins. Truncated SELENOS proteins produced by failed UGA/Sec decoding are also ubiquitinated by the CRL5(KLHDC1) complex. http://togogenome.org/gene/10090:Stra6l ^@ http://purl.uniprot.org/uniprot/Q9DBN1 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a high-affinity cell-surface receptor for retinol-binding protein RBP4 and mediates RBP4-dependent retinol uptake in the liver.|||Cell membrane|||Glycosylated.|||Highly expressed in liver and small intestine. Also expressed in spleen, kidney, colon, stomach, placenta, adipose tissue and isolated adipocytes.|||Induced in adipose tissue after high fat diet. Down-regulated by holo-RBP4, retinol and retinoic acid. http://togogenome.org/gene/10090:Or1b1 ^@ http://purl.uniprot.org/uniprot/Q8VGV7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ube4a ^@ http://purl.uniprot.org/uniprot/E9Q735|||http://purl.uniprot.org/uniprot/G3X9Y5|||http://purl.uniprot.org/uniprot/Q6A0C5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ubiquitin conjugation factor E4 family.|||Cytoplasm|||Expressed in liver, heart, brain, kidney and testis.|||The U-box domain is required for the ubiquitin protein ligase activity.|||Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. Also functions as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates.|||Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates. http://togogenome.org/gene/10090:Nalcn ^@ http://purl.uniprot.org/uniprot/Q8BXR5 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NALCN family.|||Cell membrane|||Contains 24 transmembrane helices (TM) that form four homologous functional repeats connected by intracellular linkers. Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments represent the voltage-sensor. S4 transmembrane segments lack some of the charged residues (K and R) found at every third position in the S4s of the NaV, CaV, and KV channels. Pore-forming loops (P loops) between S5 and S6 of each domain form an EEKE sodium- ion selectivity filter a mixture between the EEEE found in the CaVs and the DEKA of NaVs. Voltage-sensing domains (VSDs), formed by S1 to S4 of each domain, detect changes in membrane potential and induce the opening or closing of the ion-conducting pore domain, formed by S5 and S6.|||Deficient mice exhibit abnormal breathing at birth and die within 24 hours.|||Found in a complex with NALCN, UNC79, UNC80 and NACL1; these auxiliary subunits are indispensable for the function of the NALCN channel (By similarity). Interacts with UNC80; required for the NALCN activation/inhibition by GPCRs in neurons (PubMed:19092807, PubMed:21040849). Found in a complex with NALCN, UNC79 and UNC80; UNC80 bridges NALCN to UNC79 (PubMed:21040849). Interacts with CHRM3 (PubMed:19575010).|||Inhibited by low micromolar concentrations of Gd(3+) and high micromolar concentrations of verapamil. Insensitive to tetrodotoxin (TTX) and potentiated by low external Ca(2+) concentration.|||NALCN was also originally reported to be a voltage-independent, cation-nonselective channel which is permeable to sodium, potassium and calcium ions (PubMed:17448995). However, NALCN is recently reported to be selective only for monovalent cations and to be blocked by extracellular divalent cations (By similarity). Futhemore, coexpression of NALCN, UNC79, UNC80, and NALF1 results in voltage-dependent NALCN currents (By similarity).|||Phosphorylated on tyrosine residues.|||Voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability. NALCN channel functions as a multi-protein complex, which consists at least of NALCN, NALF1, UNC79 and UNC80. NALCN is the voltage-sensing, pore-forming subunit of the NALCN channel complex. NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations (By similarity). In addition to its role in regulating neuronal excitability, is required for normal respiratory rhythm, systemic osmoregulation by controlling the serum sodium concentration and in the regulation of the intestinal pace-making activity in the interstitial cells of Cajal (PubMed:21177381, PubMed:22508057). Plays a critical role in both maintenance of spontaneous firing of substantia nigra pars reticulata (SNr) neurons and physiological modulation of SNr neuron excitability (PubMed:27177420). NALCN channel is also activated by neuropeptides such as neurotensin and substance P (SP) through a SRC family kinases-dependent pathway (PubMed:19092807). In addition, NALCN activity is enhanced/modulated by several GPCRs, such as CHRM3 (PubMed:19092807, PubMed:19575010, PubMed:21040849).|||Widely expressed in the brain and spinal cord neurons (PubMed:17448995). Expressed also in pancreatic islet cells (PubMed:19575010). http://togogenome.org/gene/10090:Robo4 ^@ http://purl.uniprot.org/uniprot/Q8C310 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. ROBO family.|||Expressed specifically in embryo and adult vascular endothelium.|||Homozygous knockout mice exhibit a complex cardiovascular phenotype that includes a combination of aortic valve thickening with or without bicuspid aortic valve, aortic valve stenosis, regurgitation and/or ascending aortic aneurysm. In general, these phenotypes are observed with low penetrance and male predominance.|||In embryonic development of vascular endothelium, it shows a dynamic expression pattern within vessels, with expression starting in the larger axial vessels and intersomitic vessels at earlier ages, and changing to intersomitic vessel and capillary expression at later stages. At 9.0 dpc, is expressed in the central vessels, the dorsal aorta, and intersomitic vessels. At 9.5 dpc, is highly expressed in intersomitic vessels with little expression remaining in dorsal aortae. By 10.0 dpc, is detected in capillary vessels, the capillary plexus of the limb buds, and throughout the endothelium as microvessels sprout from the dorsal aortae. No expression was detected in the neural tube at 9.0 dpc and 9.5 dpc. However, it is detected within the capillaries sprouting into the neural tube, as well as in the adjacent perineural capillary plexus at 10.0 dpc. At 11.5 dpc, it is expressed in the endocardial layer of the cushions and delamination zones. By 17 dpc, it is detected in both the endothelial and interstitial cells of the developing aortic valve and endothelial cells of the proximal aorta. At 5 weeks after birth, it is localized to the endothelial layer of the ascending aorta and persists throughout postnatal development (PubMed:30455415).|||Interacts with SLIT2 and ENAH.|||Receptor for Slit proteins, at least for SLIT2, and seems to be involved in angiogenesis and vascular patterning. May mediate the inhibition of primary endothelial cell migration by Slit proteins. Involved in the maintenance of endothelial barrier organization and function (By similarity). http://togogenome.org/gene/10090:Gdi1 ^@ http://purl.uniprot.org/uniprot/P50396 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Rab GDI family.|||Cytoplasm|||High expression in brain, lower in other tissues.|||Interacts with RHOH (By similarity). Interacts with the non-phosphorylated forms of RAB1A, RAB3A, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB12, RAB35, and RAB43 (By similarity). Interacts with RAB10 (PubMed:19570034).|||Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Promotes the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Promotes the dissociation of RAB1A, RAB3A, RAB5A and RAB10 from membranes.|||trans-Golgi network http://togogenome.org/gene/10090:Or52u1 ^@ http://purl.uniprot.org/uniprot/Q8VF27 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Alad ^@ http://purl.uniprot.org/uniprot/P10518|||http://purl.uniprot.org/uniprot/Q9DD05 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the ALAD family.|||Binds 8 zinc ions per octamer. Requires four zinc ions per octamer for full catalytic activity. Can bind up to 2 zinc ions per subunit.|||Can alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor (By similarity).|||Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen (By similarity).|||Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.|||Homooctamer; active form. Homohexamer; low activity form (By similarity).|||Homooctamer; active form. Homohexamer; low activity form. http://togogenome.org/gene/10090:Mill1 ^@ http://purl.uniprot.org/uniprot/Q8HWE7 ^@ Caution|||Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MHC class I family.|||Cell membrane|||Expressed in stomach, intestine, uterus, skeletal muscle and heart.|||Heterodimer with B2M.|||In neonatal animals, highly expressed in skin where it localizes to a region of the inner root sheath of hair follicles (at protein level) (PubMed:12370446, PubMed:16920948). Also expressed in thymic medullary epithelial cells (at protein level) (PubMed:12370446, PubMed:16920948). Detected in skeletal muscle, eyes, and submandibular glands (PubMed:12370446).|||Lacks key residues involved in peptide docking and also does not require TAP (transporter involved in antigen processing) for cell surface expression, suggesting that this is a non-classical MHC class I protein which does not play a role in antigen presentation.|||N-glycosylated. http://togogenome.org/gene/10090:Xkr5 ^@ http://purl.uniprot.org/uniprot/Q5GH66|||http://purl.uniprot.org/uniprot/Q8BG78 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the XK family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxo7 ^@ http://purl.uniprot.org/uniprot/Q3U7U3 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||FBXO7-deletion mice expired without exception at the beginning of the fourth postnatal week, independently of gender. Before the fourth week, mice displayed significantly lower body and brain weights.|||Mitochondrion|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO7) formed of CUL1, SKP1, RBX1 and FBXO7. Interacts via its C-terminal proline-rich region with DLGAP5. Interacts with BIRC2. Interacts with CDK6 and promotes its interaction with D-type cyclin. Interacts (via the N-terminal Ubl domain) with PRKN. Interacts (via N-terminal region) with PINK1. Interacts with PSMF1 (By similarity).|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins and plays a role in several biological processes such as cell cycle, cell proliferation, or maintenance of chromosome stability. Recognizes and ubiquitinates BIRC2 and the cell cycle regulator DLGAP5. Plays a role downstream of PINK1 in the clearance of damaged mitochondria via selective autophagy (mitophagy) by targeting PRKN to dysfunctional depolarized mitochondria. Promotes MFN1 ubiquitination. Mediates the ubiquitination and proteasomal degradation of UXT isoform 2, thereby impairing the NF-kappa-B signaling pathway. Inhibits NF-kappa-B pathway also by promoting the ubiquitinatioin of TRAF2 (By similarity). Affects the assembly state and activity of the proteasome in the cells including neurons by ubiquitinating the proteasomal subunit PSMA2 via 'Lys-63'-linked polyubiquitin chains (PubMed:27497298). Promotes 'Lys-48'-linked polyubiquitination SIRT7, leading to the hydrogen peroxide-induced cell death (By similarity).|||The proline-rich region is important for protein-protein interactions.|||The ubiquitin-like region mediates interaction with PRKN.|||cytosol http://togogenome.org/gene/10090:Dnajc1 ^@ http://purl.uniprot.org/uniprot/Q61712 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Interacts (via J domain) with HSPA5. Interacts (via cytosolic domain) with ribosomes. Interacts (via SANT 2 domain) with SERPINA3; the interaction delays the formation of the covalent inhibitory complex SERPINA3-chymotrypsin, but does not alter the catalytic activity of SERPINA3. Interacts (via SANT 2 domain) with ITIH4 (via C-terminus); the interaction protects ITIH4 against in vitro cleavage by kallikrein (By similarity).|||May modulate protein synthesis.|||Microsome membrane|||Nucleus membrane|||Widely expressed. http://togogenome.org/gene/10090:Kdm6a ^@ http://purl.uniprot.org/uniprot/O70546|||http://purl.uniprot.org/uniprot/Q3TPN3 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UTX family.|||Component of the MLL2/3 complex (also named ASCOM complex), at least composed of KMT2D/MLL2 or KMT2C/MLL3, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A (or KDM6B), PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (By similarity). Interacts with TLE1 (PubMed:9854018). Interacts with SUPT6H (PubMed:23503590). Interacts with SMARCA4 (PubMed:21095589). Interacts with PROSER1 (By similarity).|||Escapes X chromosome inactivation.|||Expressed in brain, heart and spleen.|||Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (By similarity). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (PubMed:21095589).|||Nucleus|||Widely expressed at 13.5 dpc. http://togogenome.org/gene/10090:Snrpe ^@ http://purl.uniprot.org/uniprot/P62305 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2. Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts with SMN1; the interaction is direct. Interacts with GEMIN2 (via N-terminus); the interaction is direct. Interacts with SNRPF; the interaction is direct. Interacts with SNRPG; the interaction is direct.|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. As part of the U7 snRNP it is involved in histone 3'-end processing.|||cytosol http://togogenome.org/gene/10090:Aptx ^@ http://purl.uniprot.org/uniprot/Q7TQC5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined (PubMed:16964241). Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (By similarity). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity).|||Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT/PARP1 and p53/TP53. Interacts with NCL. Interacts (via FHA-like domain) with MDC1 (phosphorylated).|||The C2H2-type zinc finger mediates DNA-binding.|||The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4.|||The HIT domain is required for enzymatic activity.|||The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide.|||Widely expressed. Expressed in heart, liver, kidney, spleen, lung, muscle, brain stem, spinal cord, cerebellum and brain.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Efhc2 ^@ http://purl.uniprot.org/uniprot/Q059K2|||http://purl.uniprot.org/uniprot/Q9D485 ^@ Function|||Subcellular Location Annotation ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Epha6 ^@ http://purl.uniprot.org/uniprot/G1K381 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tm9sf5 ^@ http://purl.uniprot.org/uniprot/A2AFI6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.|||Membrane http://togogenome.org/gene/10090:Dpy19l1 ^@ http://purl.uniprot.org/uniprot/A6X919 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the dpy-19 family.|||Membrane|||Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins. http://togogenome.org/gene/10090:Ppl ^@ http://purl.uniprot.org/uniprot/G5E898|||http://purl.uniprot.org/uniprot/Q9R269 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plakin or cytolinker family.|||Cell membrane|||Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. May act as a localization signal in PKB/AKT-mediated signaling.|||Cytoplasm|||Expressed in the retinal lens (at protein level).|||Expressed in the upper granular cell layer of dorsal lip and tongue, palate and dorsal epidermis of newborns (PubMed:15226441). Expressed in the corneal epithelium and conjunctiva, with expression prevalent in the cytoplasm of anterior lens epithelial cells, becoming predominantly membrane expressed in epithelial cells as they elongate into fiber cells at 3 weeks of age (PubMed:19029034).|||Homodimer or a heterodimer with EVPL (By similarity). Found in a complex composed of PPL (via C-terminal linker domain), BFSP1 and BFSP2 in the retinal lens (PubMed:19029034). Within the complex interacts (via C-terminal linker domain) with BFSP2 (PubMed:19029034). Interacts with VIM (PubMed:12244133, PubMed:19029034). Binds to the PH domain of AKT1 (PubMed:12244133). Interacts with FCGR1A (By similarity). May interact with PPHLN1 (By similarity).|||cytoskeleton|||desmosome http://togogenome.org/gene/10090:Nucb2 ^@ http://purl.uniprot.org/uniprot/P81117 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance.|||Belongs to the nucleobindin family.|||Calcium-binding protein which may have a role in calcium homeostasis (PubMed:10915798). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3 (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Found in liver, heart, thymus, muscle, intestine, kidney, lung, spleen and throughout the brain, in cerebral cortex, hippocampus, hypothalamus and medulla oblongata. Nucb2 and necdin levels were higher in postmitotic neurons.|||Golgi apparatus|||Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (By similarity). Preferentially interacts with inactive rather than active GNAI3 (By similarity). Interaction with GNAI3 is inhibited when NUCB2 binds calcium, probably due to a conformational change which renders the GBA motif inaccessible (By similarity). Binds to the postmitotic growth suppressor NDN; coexpression abolishes NUCB2 secretion (PubMed:10915798).|||Membrane|||Nucleus envelope|||Perikaryon|||Secreted|||The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins). http://togogenome.org/gene/10090:Pomt1 ^@ http://purl.uniprot.org/uniprot/Q8R2R1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 39 family.|||Endoplasmic reticulum membrane|||Expressed ubiquitously at low level after 7.5 dpc. At 8.5 dpc high levels of expression are detected throughout the neural tube, and in the dorsal aspects of the neural folds of the future midbrain region and the somites. At 9.0 dpc high levels of expression are detected in the ventral domain of the neural tube, developing eye, floor plate, notochord, and gut endothelium. At 10.5 dpc expression high levels of expression are detected in the dermomyotome of the somites, limb-bud mesenchyme, mantle layer of the dorsal neural tube, and developing trigeminal ganglion.|||Mice suffer of developmental arrest around 7.5 dpc and die between 7.5 dpc and 9.5 dpc. Defects are observed in the formation of Reichert's membrane that are probably due to abnormal glycosylation and maturation of dystroglycan and impaired recruitment of laminin.|||Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient. Essentially dedicated to O-mannosylation of alpha-DAG1 and few other proteins but not of cadherins and protocaherins. http://togogenome.org/gene/10090:Abhd2 ^@ http://purl.uniprot.org/uniprot/Q9QXM0 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acylglycerol lipase activity is activated upon binding to progesterone.|||Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.|||Cell membrane|||Detected in embryos from 7 dpc to 17 dpc. Weakly expressed in heart at 9.5 dpc. Expression is detected in endothelial cells of the dorsal aorta at 10.5 dpc and disappear at 12.5 dpc. Expression in smooth muscle cells is first detected at 11.5 dpc. Strongly expressed in vitelline vessels at 12.5 dpc. Expressed in all smooth muscle cells at 16.5 dpc.|||Neointimal hyperplasia (PubMed:15721306). In lungs, decreased level of phosphatidylcholine in the bronchoalveolar lavage is observed (PubMed:19250629). Mice develop spontaneous gradual progression of emphysema (PubMed:19250629).|||Progesterone-dependent acylglycerol lipase that catalyzes hydrolysis of endocannabinoid arachidonoylglycerol (AG) from cell membrane. Acts as a progesterone receptor: progesterone-binding activates the acylglycerol lipase activity, mediating degradation of 1-arachidonoylglycerol (1AG) and 2-arachidonoylglycerol (2AG) to glycerol and arachidonic acid (AA). Also displays an ester hydrolase activity against acetyl ester, butanoate ester and hexadecanoate ester. Plays a key role in sperm capacitation in response to progesterone by mediating degradation of 2AG, an inhibitor of the sperm calcium channel CatSper, leading to calcium influx via CatSper and sperm activation (By similarity). Involved in acrosomal reaction (Probable). May also play a role in smooth muscle cells migration (PubMed:15721306).|||Widely expressed with higher expression in testis. Expressed by vascular smooth muscle cells, non vascular smooth muscle cells and heart.|||acrosome membrane http://togogenome.org/gene/10090:Rit2 ^@ http://purl.uniprot.org/uniprot/P70425 ^@ Activity Regulation|||Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alternates between an inactive form bound to GDP and an active form bound to GTP.|||Belongs to the small GTPase superfamily. Ras family.|||Binds and exchanges GTP and GDP. Binds and modulates the activation of POU4F1 as gene expression regulator.|||Cell membrane|||Expressed in ganglion cell layer (GCL), inner plexiform layer (IPL) and inner nuclear layer (INL) of the retina. Expressed in retinal ganglion cells (RGCs). Expressed in horizontal, bipolar and amacrine cells, but not Mueller glia, of the INL (at protein level). Neuron-specific (PubMed:8824319). Expressed in ganglion cell layer (GCL) and inner plexiform layer (IPL) (PubMed:23805044).|||Expressed weakly in ganglion cell layer (GCL) and inner neuroblastic layer (NBL) of the embryonic retina at 15.5 dpc. Expression increases progressively in the retina from new borns at postnatal day 2 (P2), P5, P15 to 8 week-old adult (at protein level).|||Interacts with PLXNB3 (By similarity). Interacts with AFDN, the C-terminal domain of RALGDS and RLF, but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-bound form. Binds calmodulin. Interacts with POU4F1 (via N-terminus); the interaction controls POU4F1 transactivation activity on some neuronal target genes (PubMed:12934100).|||Nucleus|||Shows rapid uncatalyzed guanine nucleotide dissociation rates, which are much faster than those of most Ras subfamily members. http://togogenome.org/gene/10090:Dnaja4 ^@ http://purl.uniprot.org/uniprot/Q9JMC3 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Membrane|||Specifically expressed in testis and heart. http://togogenome.org/gene/10090:Pld2 ^@ http://purl.uniprot.org/uniprot/P97813|||http://purl.uniprot.org/uniprot/Q3UNY4|||http://purl.uniprot.org/uniprot/Q5SXG5|||http://purl.uniprot.org/uniprot/Q6NV49 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholipase D family.|||Cell membrane|||Expressed at high levels in the hippocampus at the earliest time at which it is defined as a structure and also in ventricular neural cells as well as differentiating neurons outside of the ventricular region. Expressed during development in lower levels in mesenchymal cells derived from the neural crest that are destined to form bones of the skull.|||Function as phospholipase selective for phosphatidylcholine (PubMed:21085684). May have a role in signal-induced cytoskeletal regulation and/or endocytosis (PubMed:9395408).|||Interacts with PIP5K1B (By similarity). Interacts with EGFR (PubMed:9837959).|||Phosphorylated by FGR (By similarity). Phosphorylated on Tyr-11; most likely by EGFR (PubMed:9837959).|||Stimulated by phosphatidylinositol 4,5-bisphosphate. Is not responsive to either ADP-ribosylation factor-1 (ARF-1) or GTP-binding proteins such as RHOA.|||Ubiquitous. Highest levels in brain and lung. http://togogenome.org/gene/10090:Cep20 ^@ http://purl.uniprot.org/uniprot/Q9CZS3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP43 family.|||Cytoplasmic granule|||Homooligomer; probably required for localization to centrosomes (By similarity). Forms a complex with KIAA0753/OFIP and OFD1; within this complex may stabilize the interaction between OFD1 and KIAA0753/OFIP (PubMed:26643951). Interacts with PCM1; this interaction may be mediated by KIAA0753/OFIP (PubMed:26643951).|||Involved in the biogenesis of cilia (By similarity). Required for the recruitment of PLK1 to centrosomes and S phase progression (By similarity).|||centriolar satellite|||centriole|||centrosome|||cilium|||cilium basal body http://togogenome.org/gene/10090:Vamp3 ^@ http://purl.uniprot.org/uniprot/P63024 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type X (BoNT/X) which hydrolyzes the 53-Arg-|-Ala-54 bond and probably inhibits neurotransmitter release (PubMed:28770820). It remains unknown whether BoNT/X is ever produced, or what organisms it targets.|||Belongs to the synaptobrevin family.|||Early endosome membrane|||Interacts with BVES (via the C-terminus cytoplasmic tail). Interacts with BCAP31; involved in VAMP3 export from the endoplasmic reticulum. Interacts with BAIAP3; this interaction is increased in the presence of calcium (By similarity). Interacts with PICALM (By similarity).|||Recycling endosome membrane|||SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.|||Ubiquitinated by RNF167 at Lys-70, Lys-72 and Lys-81, regulating the recycling endosome pathway.|||synaptosome http://togogenome.org/gene/10090:Apol10a ^@ http://purl.uniprot.org/uniprot/Q8CCA5 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Pon1 ^@ http://purl.uniprot.org/uniprot/P52430 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paraoxonase family.|||Binds 2 calcium ions per subunit.|||Homodimer. Interacts with CLU.|||Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification.|||Plasma, liver, kidney, heart, brain, small intestine and lung. In the plasma, associated with HDL.|||The preferential association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo AI. The retained signal peptide may allow transfer of the protein between phospholipid surfaces.|||The signal sequence is not cleaved.|||extracellular space http://togogenome.org/gene/10090:Tead3 ^@ http://purl.uniprot.org/uniprot/F8VPU0|||http://purl.uniprot.org/uniprot/P70210 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in embryos as well as in many adult tissues.|||Interacts with YAP1 and WWTR1/TAZ.|||Nucleus|||Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.|||Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction (By similarity).|||Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon. http://togogenome.org/gene/10090:Cep57l1 ^@ http://purl.uniprot.org/uniprot/B2RR53|||http://purl.uniprot.org/uniprot/G5E828|||http://purl.uniprot.org/uniprot/Q8VDS7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the translokin family.|||Centrosomal protein which may be required for microtubule attachment to centrosomes.|||centrosome http://togogenome.org/gene/10090:Spatc1 ^@ http://purl.uniprot.org/uniprot/Q148B6 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the speriolin family.|||Cytoplasm|||Expressed in testis. Expressed in pachyten spermatocytes, spermatids and epididymal sperm (at protein level).|||Found in a complex with CDC20, CDC27 and TUBG1. Interacts with CDC20.|||centrosome http://togogenome.org/gene/10090:Trim71 ^@ http://purl.uniprot.org/uniprot/Q1PSW8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Belongs to the TRIM/RBCC family.|||E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance (PubMed:19898466). Binds to miRNAs and associates with AGO2, participating in post-transcriptional repression of transcripts such as CDKN1A. Facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal by repressing CDKN1A expression (PubMed:22735451). In addition, participates in post-transcriptional mRNA repression in a miRNA independent mechanism (PubMed:23125361). Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development: positively regulates FGF signaling by controlling the stability of SHCBP1 (PubMed:22735451). Specific regulator of miRNA biogenesis. miRNA Binds MIR29A hairpin and postranscriptionally modulates MIR29A levels, which indirectly regulates TET proteins expression (By similarity).|||Embryonic lethality at 9.5 dpc, due to a neural tube closure defect in the anterior craniofacial region of the neural tube, corresponding to the forebrain/midbrain boundary. Reduced cell proliferation in the neuroepithelium.|||Expression is first detected at 8.5 dpc, increases to highest levels at 14.5 dpc and remains elevated through the newborn stage. Expressed in developing limb buds and tail buds starting from 9.5 dpc. At 9.5 dpc, expression is prominent in the entire embryo, with the exception of the primordial cardiac sac. At 10.5 dpc, expression reduces to the neuroepithelium, branchial arches, spinal cord, somites, limb, and tail buds. At the onset of central nervous system development, the neuroepithelium shows a prominent staining between 9.5 dpc and 10.5 dpc. Thereafter, expression is unevenly distributed in a progressively thinner layer along the inner surface of the ventricle. Expression is intense at the bumps corresponding to the nascent limb buds around 10.5 dpc. Shortly thereafter, as the limb buds emerge from the body and expand, expression declines and is limited to the most distal surface at 12.5 dpc. At 13.5 dpc it is no longer possible to identify expression in either the developing nervous system, the limb or the tail buds. From postnatal day 10 (P10) to the adulthood, expressed in cells lining the wall of the four ventricles of the postnatal brain (PubMed:25883935).|||Highly expressed in undifferentiated embryonic stem cells (ESCs). Expressed in the epiblast and in interfollicular epidermal stem cells during early development. Also expressed in male germ cells and in the reproductive tract. Highly expressed in neuroepithelial cells, and its expression declines as neurogenesis proceeds (at protein level). Expressed in ependymal cells of the brain (PubMed:25883935).|||Interacts (via NHL repeats) with AGO2; the interaction increases in presence of RNA (PubMed:19898466, PubMed:22508726, PubMed:22735451). Interacts with HSP90AA1. Interacts (via NHL repeats) with MOV10, PABPC1, PUM1, PUM2, STAU2, XRN1 and XRN2 in an RNA-dependent manner (By similarity). Interacts with SHCBP1; leading to enhance its stability (PubMed:22508726).|||Negatively regulated by the microRNA (miRNA) let-7 which causes degradation of the mRNA encoding this protein. This requires a let-7 complementary site (LCS) in the 3'-UTR of the mRNA encoding this protein.|||P-body|||Reported to mediate ubiquitination and subsequent degradation of AGO2 (PubMed:19898466). However, this result is subject to discussion and later reports suggest that, while it interacts with AGO2, it is not involved in AGO2 ubiquitination (PubMed:22508726, PubMed:22735451).|||The NHL domain, containing the 6 NHL repeats, is necessary and sufficient to target RNA but not to repress mRNA. The minimal region needed to execute repression consists of the coiled coil domain and the Filamin repeat. The RING-type domain is dispensable for mRNA repression. http://togogenome.org/gene/10090:Riok1 ^@ http://purl.uniprot.org/uniprot/Q922Q2 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the precursor of the 40S ribosome subunit. Interacts (via its N-terminus) with PRMT5 (via its N-terminus). Interacts with WDR77 (By similarity). Found in a PRMT5 complex composed of PRMT5, WDR77 and RIOK1 (By similarity). Interacts (via its C-terminus) with NCL; this interaction targets NCL for PRTM5 methylation (By similarity).|||Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.|||Intron retention.|||Involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in processing of 18S-E pre-rRNA to the mature 18S rRNA. Required for the recycling of NOB1 and PNO1 from the late 40S precursor (By similarity). The association with the very late 40S subunit intermediate may involve a translation-like checkpoint point cycle preceeding the binding to the 60S ribosomal subunit (By similarity). Despite the protein kinase domain is proposed to act predominantly as an ATPase (By similarity). The catalytic activity regulates its dynamic association with the 40S subunit (By similarity). In addition to its role in ribosomal biogenesis acts as an adapter protein by recruiting NCL/nucleolin the to PRMT5 complex for its symmetrical methylation (By similarity).|||cytosol http://togogenome.org/gene/10090:Spata9 ^@ http://purl.uniprot.org/uniprot/Q9D9R3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ In the 7-week-old, expressed in spermatogenic cells at every stage, (spermatogonium, primary spermatocyte, spermatid, and mature sperm). Expression levels increased during spermatogenesis. No expression in Leydig cells.|||May play at role in testicular development/spermatogenesis and may be an important factor in male infertility.|||Membrane http://togogenome.org/gene/10090:Zfp366 ^@ http://purl.uniprot.org/uniprot/Q6NS86 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in immature and mature dendritic cells (DCs).|||Has transcriptional repression activity. Acts as corepressor of ESR1; the function seems to involve CTBP1 and histone deacetylases.|||Interacts with ESR1 and NRIP1. Interacts (via PXDLS motif) with CTBP1.|||Nucleus http://togogenome.org/gene/10090:St6gal2 ^@ http://purl.uniprot.org/uniprot/Q76K27 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Golgi stack membrane|||Mainly expressed in brain and embryo. Very low expression is also detected in spleen, oviduct, lung and skeletal muscle.|||Transfers sialic acid from the donor of substrate CMP-sialic acid to galactose containing acceptor substrates. Has alpha-2,6-sialyltransferase activity toward oligosaccharides that have the Gal-beta-1,4-GlcNAc sequence at the non-reducing end of their carbohydrate groups, but it has weak or no activities toward glycoproteins and glycolipids. http://togogenome.org/gene/10090:Klhl20 ^@ http://purl.uniprot.org/uniprot/Q8VCK5 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Approximately 50% of mice die until day 28 of postnatal development (P28). Mice that survive beyond P28 are indistinguishable at birth, but show a progressive corneal dystrophy, associated with an epithelial hyperplasia and an altered corneal epithelial cell differentiation.|||Component of the BCR(KLHL20) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL20 and RBX1. Interacts with PDZ-RhoGEF/ARHGEF11, DAPK1, PML and CORO7. Interacts with F-actin. Interacts with IFN-gamma (IFNG) (By similarity). Interacts (via kelch repeats) with IVNS1ABP (via kelch repeats); this interaction blocks the assembly of CUL3-KLHL20 complex (By similarity).|||Nucleus|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of DAPK1, leading to its degradation by the proteasome, thereby acting as a negative regulator of apoptosis. The BCR(KLHL20) E3 ubiquitin ligase complex also specifically mediates 'Lys-33'-linked ubiquitination. Involved in anterograde Golgi to endosome transport by mediating 'Lys-33'-linked ubiquitination of CORO7, promoting interaction between CORO7 and EPS15, thereby facilitating actin polymerization and post-Golgi trafficking. Also acts as a regulator of endothelial migration during angiogenesis by controlling the activation of Rho GTPases. The BCR(KLHL20) E3 ubiquitin ligase complex acts as a regulator of neurite outgrowth by mediating ubiquitination and degradation of PDZ-RhoGEF/ARHGEF11 (By similarity).|||axon|||dendrite|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Vmn1r232 ^@ http://purl.uniprot.org/uniprot/A2RTT5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ttc1 ^@ http://purl.uniprot.org/uniprot/Q91Z38 ^@ Subunit ^@ Interacts with the GAP domain of NF1. Interacts (via TPR repeats) with HSP90AA1 and HSPA8. http://togogenome.org/gene/10090:Rrp8 ^@ http://purl.uniprot.org/uniprot/E9PVA2|||http://purl.uniprot.org/uniprot/Q9DB85 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. RRP8 family.|||Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8.|||Component of the eNoSC complex.|||Essential component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the complex, RRP8 binds to H3K9me2 and probably acts as a methyltransferase.|||Essential component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the complex, RRP8 binds to H3K9me2 and probably acts as a methyltransferase. Its substrates are however unknown (By similarity).|||nucleolus http://togogenome.org/gene/10090:Kcnk18 ^@ http://purl.uniprot.org/uniprot/Q6VV64 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Cell membrane|||Detected in brain cortex, cerebellum, dorsal root ganglion, spinal cord and testis. High expression in trigeminal ganglion, also expressed in autonomic nervous system ganglia such as the stellate ganglion and paravertebral sympathetic ganglia. Expressed in all adult spinal cord and brain regions, with slightly higher expression in thalamus, hypothalamus, hippocampus and posterior corte (at protein level). In non-neuronal tissues, substantial expression found in lung and heart and weal expression in liver, testis, kidney, small intestine and spleen.|||Expression appears in trigeminal ganglion and dorsal root ganglia from 15.5 dpc and increased through 18 dpc to reach a peak in newborn mouse postnatal day 1.|||Interacts with calcineurin. Interacts with YWHAH, in a phosphorylation-dependent manner.|||N-glycosylated.|||Outward rectifying potassium channel. Produces rapidly activating outward rectifier K(+) currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation.|||Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances channel activity.|||Regulated by extracellular protons whereas human ortholog is not. His-132 is responsible for proton-dependent specific activity. http://togogenome.org/gene/10090:Rpl11 ^@ http://purl.uniprot.org/uniprot/Q9CXW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL5 family.|||Component of the large ribosomal subunit (LSU) (PubMed:36517592). Part of a LSU subcomplex, the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11 (By similarity). Interacts with PML (PubMed:15195100). Interacts with MDM2; negatively regulates MDM2-mediated TP53 ubiquitination and degradation (PubMed:15195100, PubMed:21804542). Interacts with NOP53; retains RPL11 into the nucleolus (PubMed:21804542).|||Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:36517592). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:36517592). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:36517592). As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs (PubMed:36517592). It also couples ribosome biogenesis to p53/TP53 activation (PubMed:21804542). As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53 (PubMed:21804542). Promotes nucleolar location of PML (PubMed:15195100).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Rab11fip1 ^@ http://purl.uniprot.org/uniprot/Q9D620 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and phagocytosis (By similarity).|||Homooligomer. Interacts with RAB4A, RAB11A, RAB11B and RAB25 (By similarity).|||Recycling endosome|||phagosome membrane http://togogenome.org/gene/10090:Rpp25l ^@ http://purl.uniprot.org/uniprot/Q99JH1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the histone-like Alba family.|||May be a component of ribonuclease P or MRP.|||Nucleus http://togogenome.org/gene/10090:Ppef1 ^@ http://purl.uniprot.org/uniprot/O35655 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Activated by calcium.|||Belongs to the PPP phosphatase family.|||Binds 2 manganese ions per subunit.|||In the embryo it is almost exclusively expressed in the peripheral nervous system, within sensory neurons of cranial and dorsal root ganglia. Otherwise found in fetal inner ear and a small group of neurons in the midbrain/pons junction.|||May have a role in the recovery or adaptation response of photoreceptors. May have a role in diverse sensory neurons and in development.|||Up-regulated at 12.3 dpc in dorsal root ganglia (DRG) and in some sensory cranial ganglia. A slightly decreased expression could still be detected in sensory ganglia at 16.5 dpc. It is not known if expression in sensory neurons persists in adult life. http://togogenome.org/gene/10090:Cep97 ^@ http://purl.uniprot.org/uniprot/Q9CZ62 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a key negative regulator of ciliogenesis in collaboration with CCP110 by capping the mother centriole thereby preventing cilia formation. Required for recruitment of CCP110 to the centrosome (By similarity).|||Interacts with CALM1, CEP76, KIF24 and TALPID3 (By similarity). Interacts with CCP110 (PubMed:35301795). ENKD1 competes with CEP97 for binding to CCP110, destabilizing the interaction between CP110 and CEP97 which promotes the removal of CCP110 and CEP97 from the mother centriole and allows the initiation of ciliogenesis (PubMed:35301795). Via its interaction with CCP110, may indirectly interact with HERC2 and NEURL4 (By similarity). Interacts with MPHOSPH9 (By similarity).|||centriole|||centrosome http://togogenome.org/gene/10090:Mtrr ^@ http://purl.uniprot.org/uniprot/Q8C1A3 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Female mice have more resorptions and more delayed embryos per litter as well as embryonic delays and defects: placentae of mothers are smaller and their embryos are smaller and display myocardial hypoplasia and a higher incidence of ventricular septal defects per litter (PubMed:18413293). Epigenetic transmission of developmental disorders between generations: a hypomorphic mutation disrupts folate metabolism and is associated with effects on offspring development that are transmitted transgenerationally. The epigenetic influences caused by Mtrr hypomorphic deficiency in mice leads to 2 distinctive phenotypes: (1) an atypical uterine environment in their wild-type daughters that causes growth defects in their wild-type grandprogeny and (2) congenital malformations in their wild-type grandprogeny due to epigenetic inheritance via the germline, the effects of which persist for at least up to 4 wild-type generations after an Mtrr-deficient maternal ancestor. These effects are associated with altered DNA methylation patterns (PubMed:24074862).|||Forms a multiprotein complex with MMACHC, MMADHC and MTR.|||It is debated whether the reduction of free aquacob(II)alamin occurs spontaneously or is enzyme catalyzed.|||Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin. Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (By similarity). Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (PubMed:24074862). Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme. Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (By similarity). http://togogenome.org/gene/10090:Cmtm5 ^@ http://purl.uniprot.org/uniprot/Q9D6G9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chemokine-like factor family.|||Membrane http://togogenome.org/gene/10090:Armh3 ^@ http://purl.uniprot.org/uniprot/Q6PD19 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ARMH3 family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||Golgi apparatus membrane|||Interacts with PI4KB. Interacts with GBF1.|||Involved in GBF1 recruitment, Golgi maintenance and protein secretion. http://togogenome.org/gene/10090:Vgll4 ^@ http://purl.uniprot.org/uniprot/Q80V24 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the vestigial family.|||Interacts with TEFs. Interacts with IRF2BP2 (By similarity).|||May act as a specific coactivator for the mammalian TEFs.|||Nucleus http://togogenome.org/gene/10090:Nkx1-1 ^@ http://purl.uniprot.org/uniprot/G3UXB3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Autoregulated by a negative-feedback mechanism in the ventral midbrain and a positive-feedback mechanism in the midbrain-hindbrain boundary region and the eyes.|||Belongs to the NK-1 homeobox family.|||Detected as early as embryonic stage 10.5 dpc in the ventral mesencephalon, metencephalon, and ventral neural tube and continues to be expressed from this embryonic stage onward, predominantly in the ventral neural tube and the mid/hindbrain boundary region. In the later stages, 12.5 to 16.5 dpc, expression in the brain is detected more specifically in the pons and medulla oblongata.|||Homozygous knockout mice for Sax2 exhibit growth retardation starting immediately after birth and leading to premature death within the first 3 weeks postnatal. Mice do not exhibit any obvious abnormal behavior or motor skills. All mice show normal suckling behavior, but at 2 or 3 days prior to their death, they become lethargic and show signs of wasting. The few homozygous animals surviving to adulthood are fertile, but all the offspring from homozygous intermatings die within 4 days postnatally (PubMed:14645517, PubMed:17879320). At 2 weeks postnatal days, mice lack subcutaneous fat and intra-abdominal epididymal and mesenteric white adipose tissue (WAT) (PubMed:17879320).|||May be required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis, possibly by regulating the transcription of specific factors involved in energy balance.|||Nucleus http://togogenome.org/gene/10090:Krt87 ^@ http://purl.uniprot.org/uniprot/Q6IMF0 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Selenof ^@ http://purl.uniprot.org/uniprot/Q9ERR7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the selenoprotein M/F family.|||Endoplasmic reticulum lumen|||Forms a tight complex with UGGT1/UGCGL1 (PubMed:11278576). Interacts with UGGT2/UGCGL2 (By similarity). Interacts with RDH11 (By similarity).|||May be involved in redox reactions associated with the formation of disulfide bonds (By similarity). May contribute to the quality control of protein folding in the endoplasmic reticulum. May regulate protein folding by enhancing the catalytic activity of UGGT1/UGCGL1 and UGGT2/UGCGL2 (By similarity). http://togogenome.org/gene/10090:Syndig1 ^@ http://purl.uniprot.org/uniprot/A2ANU3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||Brain-specific. Expressed in Purkinje neurons in cerebellum. Also detected in the hippocampus. Found at excitatory synapses and postsynaptic cells.|||Cell membrane|||Early endosome membrane|||Expressed during synaptogenesis. Found at the cell surface of excitatory synapses.|||Homodimer. Interacts with GRIA1 and GRIA2.|||May regulate AMPA receptor content at nascent synapses, and have a role in postsynaptic development and maturation.|||Postsynaptic density membrane|||Synapse|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Mmp2 ^@ http://purl.uniprot.org/uniprot/P33434|||http://purl.uniprot.org/uniprot/Q3UG07 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 4 Ca(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||Cytoplasm|||Induced by oxidative stress.|||Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B (By similarity).|||Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.|||Membrane|||Mitochondrion|||Nucleus|||PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrin alpha-v/beta-3 on the surface of blood vessels (By similarity).|||Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro (By similarity).|||Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3) (By similarity). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3 (By similarity).|||Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Gusb ^@ http://purl.uniprot.org/uniprot/P12265 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 2 family.|||Endoplasmic reticulum|||Homotetramer.|||Inhibited by L-aspartic acid.|||Lysosome|||Plays an important role in the degradation of dermatan and keratan sulfates. http://togogenome.org/gene/10090:Trf ^@ http://purl.uniprot.org/uniprot/Q921I1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transferrin family.|||Expressed by the liver and secreted in plasma.|||Monomer.|||Secreted|||Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. http://togogenome.org/gene/10090:Fgfr4 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZY3|||http://purl.uniprot.org/uniprot/Q03142 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.|||Cell membrane|||Endoplasmic reticulum|||Endosome|||Expressed in the developing gut endoderm, in myotomally derived skeletal muscle, the adrenal cortex, kidney and condensing cartilage.|||Isoform 1 and isoform 2 are expressed in lung and proliferating myoblasts and myotubes of primary myogenic cells (at protein level). Isoform 1 and isoform 2 are expressed in liver, muscle, spleen, heart, lung, kidney and in primary myogenic cells.|||Isoform 1 and isoform 2 are up-regulated by estradiol during myogenic differentiation and down-regulated in fully developed myotubes.|||Membrane|||Monomer. Homodimer after ligand binding. Interacts with FGF1, FGF2, FGF4, FGF6, FGF8, FGF9, FGF16, FGF17, FGF18, FGF19, FGF21 and FGF23 (in vitro). Binding affinity for FGF family members is enhanced by interactions between FGFs and heparan sulfate proteoglycans. Interacts with KLB; this strongly increases the affinity for FGF19 and FGF23. Affinity for FGF19 is strongly increased by KLB and sulfated glycosaminoglycans. KLB and KL both interact with the core-glycosylated FGFR4 in the endoplasmic reticulum and promote its degradation, so that only FGFR4 with fully mature N-glycans is expressed at the cell surface. Identified in a complex with NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with MMP14 and HIP1. Interacts with STAT3 (By similarity).|||N-glycosylated. Isoform 1 and isoform 2 are glycosylated. Full maturation of the glycan chains in the Golgi is essential for high affinity interaction with FGF19 (By similarity).|||No visible phenotype. Mice display an elevated bile acid pool and elevated excretion of bile acids, due to loss of normal regulation of CYP7A1, the rate-limiting enzyme in bile acid synthesis. When on a normal diet, mice are prone to develop increased levels of white adipose tissue, hyperlipidemia, hypercholesterolemia, glucose intolerance and insulin resistance. Mice lacking both FGFR3 and FGFR4 display pronounced dwarfism, and while their lungs appear normal at birth, they are completely blocked in alveogenesis and do not form secondary septae to delimit alveoli. These mice also show elevated serum levels of 1,25-dihydroxyvitamin D3 and reduced serum phosphorus levels.|||Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).|||Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Plays a role in postnatal lung development. May be involved in the development of skeletal muscle cell lineages.|||Ubiquitinated. Subject to proteasomal degradation when not fully glycosylated (By similarity). http://togogenome.org/gene/10090:Ralgds ^@ http://purl.uniprot.org/uniprot/Q03385 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expressed in the ovarian oocytes from the primary follicle stage to the antral follicle stage (at protein level). Expressed in preimplantation embryos until the early 2-cell stage, decreasing thereafter.|||Functions as a guanine nucleotide exchange factor (GEF) activating either RalA or RalB GTPases and plays an important role in intracellular transport. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap (PubMed:27773821). During bacterial clearance, recognizes 'Lys-33'-linked polyubiquitinated TRAF3 and subsequently mediates assembly of the exocyst complex (By similarity).|||Interacts with RIT1 and RIT2 (By similarity). Interacts with OOG1 (PubMed:16580637). Interacts with TRAF3 (By similarity). Interacts with HRAS (PubMed:27773821).|||Nucleus|||Phosphorylation of Tyr-752 by MET blocks HRAS binding.|||The Ras-associating domain interacts with Ras. http://togogenome.org/gene/10090:Or4a15 ^@ http://purl.uniprot.org/uniprot/A2AVK5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atxn7l3b ^@ http://purl.uniprot.org/uniprot/Q3UD01 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SGF11 family.|||By binding to ENY2, interferes with the nuclear functions of the deubiquitinase (DUB) module of the SAGA complex which consists of ENY2, ATXN7, ATXN7L3 and the histone deubiquitinating component USP22. Affects USP22 DUB activity toward histones indirectly by changing the subcellular distribution of ENY2 and altering ENY2 availability for ATXN7L3 interaction. Regulates H2B monoubiquitination (H2Bub1) levels through cytoplasmic sequestration of ENY2 resulting in loss of nuclear ENY2-ATXN7L3 association which destabilizes ATXN7L3. Affects protein expression levels of ENY2 and ATXN7L3.|||Cytoplasm|||Encoded by an expressed retrotransposed copy of the Atxn7l3 locus that emerged prior to the speciation event separating primates and rodents.|||Interacts strongly with ENY2. Interacts weakly with USP22. http://togogenome.org/gene/10090:Capza2 ^@ http://purl.uniprot.org/uniprot/P47754|||http://purl.uniprot.org/uniprot/Q5DQJ3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the F-actin-capping protein alpha subunit family.|||F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.|||Heterodimer of an alpha and a beta subunit.|||Heterodimer of an alpha and a beta subunit. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5. Interacts with RCSD1/CAPZIP (By similarity). Directly interacts with CRACD; this interaction decreases binding to actin (By similarity). http://togogenome.org/gene/10090:Dek ^@ http://purl.uniprot.org/uniprot/Q7TNV0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Found in a mRNA splicing-dependent exon junction complex (EJC) with DEK, RBM8A, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with histones H2A, H2B, H3, H4, acetylated histone H4, non-phosphorylated DAXX and HDAC2. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Binds DNA (By similarity).|||Involved in chromatin organization.|||Nucleus|||Phosphorylated by CK2. Phosphorylation fluctuates during the cell cycle with a moderate peak during G(1) phase, and weakens the binding of DEK to DNA (By similarity). http://togogenome.org/gene/10090:Rbmx2 ^@ http://purl.uniprot.org/uniprot/Q8R0F5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IST3 family.|||Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus|||Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed of at least 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Component of the minor spliceosome, which splices U12-type introns (By similarity). http://togogenome.org/gene/10090:Slc43a1 ^@ http://purl.uniprot.org/uniprot/A2ATS4|||http://purl.uniprot.org/uniprot/G3X8X3|||http://purl.uniprot.org/uniprot/Q8BSM7 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC43A transporter (TC 2.A.1.44) family.|||By nutrient starvation.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in the kidney cortex as well as liver, pancreas, and skeletal muscle (PubMed:19443642). In kidney expressed in the glomerular tuft (at protein level) (PubMed:19443642). Expressed in liver, skeletal muscle and pancreas (at protein level) (PubMed:17322374).|||Membrane|||Uniport that mediates the transport of neutral amino acids such as L-leucine, L-isoleucine, L-valine, and L-phenylalanine (PubMed:17322374). The transport activity is sodium ions-independent, electroneutral and mediated by a facilitated diffusion (PubMed:17322374). http://togogenome.org/gene/10090:Isyna1 ^@ http://purl.uniprot.org/uniprot/Q9JHU9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the myo-inositol 1-phosphate synthase family.|||Cytoplasm|||In testis, it is expressed in Sertoli cells. Highly expressed in 2 types of germ cells, pachytene spermatocytes and round spermatids.|||Key enzyme in myo-inositol biosynthesis pathway that catalyzes the conversion of glucose 6-phosphate to 1-myo-inositol 1-phosphate in a NAD-dependent manner. Rate-limiting enzyme in the synthesis of all inositol-containing compounds (By similarity). http://togogenome.org/gene/10090:Dut ^@ http://purl.uniprot.org/uniprot/Q9CQ43 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dUTPase family.|||Catalyzes the cleavage of 2'-deoxyuridine 5'-triphosphate (dUTP) into 2'-deoxyuridine 5'-monophosphate (dUMP) and inorganic pyrophosphate and through its action efficiently prevents uracil misincorporation into DNA and at the same time provides dUMP, the substrate for de novo thymidylate biosynthesis (By similarity). Inhibits peroxisome proliferator-activated receptor (PPAR) activity by binding of its N-terminal to PPAR, preventing the latter's dimerization with retinoid X receptor (By similarity). Essential for embryonic development (PubMed:30987342).|||Embryos reach the blastocyst stage, however, they die shortly after implantation and analysis of pre-implantation embryos indicates perturbed growth of both inner cell mass and trophectoderm.|||Homotrimer.|||Nucleus|||Phosphorylated in vivo on Ser-11, a reaction that can be catalyzed in vitro by CDC2. http://togogenome.org/gene/10090:Gfpt2 ^@ http://purl.uniprot.org/uniprot/Q9Z2Z9 ^@ Function ^@ Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. http://togogenome.org/gene/10090:Hp ^@ http://purl.uniprot.org/uniprot/Q3UBS3|||http://purl.uniprot.org/uniprot/Q61646 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although homologous to serine proteases, it has lost all essential catalytic residues and has no enzymatic activity.|||As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway (By similarity).|||As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.|||Belongs to the peptidase S1 family.|||Expressed by the liver and secreted in plasma.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||Tetramer of two alpha and two beta chains; disulfide-linked (By similarity). The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers (By similarity). Interacts with CD163 (By similarity). Interacts with ERGIC3 (By similarity).|||Tetramer of two alpha and two beta chains; disulfide-linked (By similarity). The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers (By similarity). Interacts with CD163 (By similarity). Interacts with ERGIC3.|||The beta chain mediates most of the interactions with both subunits of hemoglobin, while the alpha chain forms the homodimeric interface. http://togogenome.org/gene/10090:Ccnq ^@ http://purl.uniprot.org/uniprot/Q8QZR8 ^@ Function|||Similarity|||Subunit ^@ Activating cyclin for the cyclin-associated kinase CDK10.|||Associates with CDK10 to promote its kinase activity.|||Belongs to the cyclin family. Cyclin-like FAM58 subfamily. http://togogenome.org/gene/10090:Spi1 ^@ http://purl.uniprot.org/uniprot/P17433|||http://purl.uniprot.org/uniprot/Q3U5L4 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Binds DNA as a monomer. Can form homomers (By similarity). Directly interacts with CEBPD/NF-IL6-beta; this interaction does not affect DNA-binding properties of each partner (PubMed:7594592). Interacts with NONO/p54(nrb) (PubMed:8626664). Interacts with RUNX1/AML1 (By similarity). Interacts with GFI1; the interaction represses SPI1 transcriptional activity, hence blocks SPI1-induced macrophage differentiation of myeloid progenitor cells (PubMed:17197705). Interacts with CEBPE (By similarity). Interacts with IRF4/Pip and IRF8 (By similarity). Interacts with JUN (By similarity). Interacts with RB1 (By similarity). Interacts with TBP (By similarity).|||Expressed in spleen, thymus and bone-marrow macrophages.|||Knockout embryos die at a late gestational stage, with no viable embryo after day 18 of gestation. Mutant embryos produce normal numbers of megakaryocytes and erythroid progenitors, but some show an impairment of erythroblast maturation. They exhibit a multilineage defect in the generation of progenitors for B and T lymphocytes, monocytes and granulocytes.|||May be involved in murine acute Friend erythroleukemia. It is a target region for SFFV proviral insertion.|||Nucleus|||Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites (PubMed:8079170). Once in open chromatin, can directly control gene expression by binding genetic regulatory elements and can also more broadly influence transcription by recruiting transcription factors, such as interferon regulatory factors (IRFs), to otherwise inaccessible genomic regions (By similarity). Transcriptionally activates genes important for myeloid and lymphoid lineages, such as CSF1R (By similarity). Transcriptional activation from certain promoters, possibly containing low affinity binding sites, is achieved cooperatively with other transcription factors. FCER1A transactivation is achieved in cooperation with GATA1 (By similarity). May be particularly important for the pro- to pre-B cell transition (PubMed:8079170). Binds (via the ETS domain) onto the purine-rich DNA core sequence 5'-GAGGAA-3', also known as the PU-box (PubMed:2180582). In vitro can bind RNA and interfere with pre-mRNA splicing (PubMed:8626664).|||Transcriptional activity at macrophage-specific genes is inhibited by interaction with GFI1, which results in inhibition of SPI1-induced macrophage differentiation of myeloid progenitor cells, but not that of the granulocyte lineage. http://togogenome.org/gene/10090:Vmn1r74 ^@ http://purl.uniprot.org/uniprot/Q8R290 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rpl23 ^@ http://purl.uniprot.org/uniprot/P62830 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL14 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Ssxa1 ^@ http://purl.uniprot.org/uniprot/B1AUS7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SSX family.|||Could act as a modulator of transcription.|||Nucleus|||Specifically expressed in testis (at protein level). Not detected in other tissues tested (at protein level). http://togogenome.org/gene/10090:Or5ac19 ^@ http://purl.uniprot.org/uniprot/Q7TS38 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fpr-rs4 ^@ http://purl.uniprot.org/uniprot/A4FUQ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in 0.6 % of a subset of sensory neurons located in the apical layer of the vomeronasal organ. Each neuron appears to express only one receptor gene.|||May have an olfactory function associated with the identification of pathogens or of pathogenic states. http://togogenome.org/gene/10090:Usp28 ^@ http://purl.uniprot.org/uniprot/Q5I043 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. USP28 subfamily.|||Degraded upon nickel ion level or hypoxia exposure.|||Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBXW7) complex. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells.|||Interacts with ZNF304. Interacts with PRKD1. Interacts with TP53BP1. Interacts with FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC.|||Phosphorylated upon DNA damage at Ser-67 and Ser-720, by ATM or ATR. Phosphorylated by PRKD1.|||nucleoplasm http://togogenome.org/gene/10090:Ormdl1 ^@ http://purl.uniprot.org/uniprot/Q921I0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORM family.|||Ceramide-sensitive subunit of the serine palmitoyltransferase (SPT) complex, which is also composed of SPTLC1, SPTLC2/3 and SPTSSA/B.|||Ceramides bind to ORMDL3 N-terminus and stabilize it in a conformation that physically restricts the accessibility of the substrates to their binding sites in the serine palmitoyltransferase (SPT) complex, hence inhibiting SPT catalytic activity. In the absence of ceramides, the N-terminus is flexible and permits substrate binding, thus liberating SPT from inhibition.|||Endoplasmic reticulum membrane|||No overt phenotype; due to the redundancy with other ORMDL proteins (PubMed:31880535). Simultaneous knockdown of ORMDL1 and ORMDL2 do not exhibit any visible phenotype; they remain fertile and show no sign of neurodegeneration (PubMed:31880535). Double knockdown of ORMDL1 and ORMDL3 show elevated brain levels of sphingolipids, compared with single ORMDL3 knockout and wild-type animals (PubMed:31880535). At 8 weeks of age, both male and female ORMDL1/3 double knockout mice weigh significantly less than wild-type mice and exhibit impaired myelination and motor-function abnormalities (PubMed:31880535). The triple knockout ORMDL1, ORMDL2 and ORMDL3 is not viable (PubMed:31880535).|||Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:31880535). When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (By similarity). http://togogenome.org/gene/10090:Scgn ^@ http://purl.uniprot.org/uniprot/Q91WD9 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Secreted|||secretory vesicle membrane http://togogenome.org/gene/10090:Rps29 ^@ http://purl.uniprot.org/uniprot/P62274 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS14 family.|||Binds 1 zinc ion per subunit.|||Component of the 40S small ribosomal subunit.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm|||Rough endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Dnajb9 ^@ http://purl.uniprot.org/uniprot/Q9QYI6 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Co-chaperone for Hsp70 protein HSPA5/BiP that acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). J domain-containing co-chaperones stimulate the ATPase activity of Hsp70 proteins and are required for efficient substrate recognition by Hsp70 proteins (PubMed:11836248). In the unstressed endoplasmic reticulum, interacts with the luminal region of ERN1/IRE1 and selectively recruits HSPA5/BiP: HSPA5/BiP disrupts the dimerization of the active ERN1/IRE1 luminal region, thereby inactivating ERN1/IRE1 (By similarity). Also involved in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins (PubMed:22267725). Required for survival of B-cell progenitors and normal antibody production (PubMed:25222125).|||Endoplasmic reticulum lumen|||Interacts with HSPA5/BiP; interaction is direct (PubMed:11836248). Interacts with ERN1/IRE1 (via the luminal region) (By similarity). Interacts with DERL1 (PubMed:22267725).|||Not N-glycosylated.|||Perinatal death in approximately half of knockout mice (PubMed:24336520). Death is caused by fetal growth restriction, reduced hepatic glycogen stores and hypoglycemia (PubMed:24336520). Surviving adult mice display constitutive endoplasmic reticulum stress in multiple cells and tissues (PubMed:24336520). Elevated endoplasmic reticulum stress in pancreatic beta cells is associated with beta cell loss, hypoinsulinemia and glucose intolerance (PubMed:24336520) Conditional knockout mice lacking Dnajb9 in bone marrow show impaired hematopoiesis: the number of myeloid cells is increased, while the number of erythroid and B lymphoid cells is reduced (PubMed:25222125). B-cell defects cause decreased survival of B-cell precursors, including large and small pre-B, and immature B-cells (PubMed:25222125).|||The J domain stimulates the ATPase activity of HSPA5/BiP, while the divergent targeting domain is required for efficient substrate recognition by HSPA5/BiP. The divergent targeting domain specifically recognizes and binds to aggregation-prone sequences.|||Was initially thought to be an integral membrane protein (PubMed:11836248). However, it was later shown that it is a soluble luminal protein localized in the endoplasmic reticulum lumen. http://togogenome.org/gene/10090:Ecd ^@ http://purl.uniprot.org/uniprot/Q9CS74 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ECD family.|||Cytoplasm|||Embryonic lethal.|||Interacts with TP53, MDM2, TXNIP. Interacts (phosphorylated) with PIH1D1. Interacts with RUVBL1 mediating the PIH1D1-independent association with the R2TP complex. Interacts with RB1, RBL1 and RBL2; ECD competes with E2F1 for binding to hypophospshorylated RB1. Interacts with EP300.|||Nucleus|||Phosphorylated predominantly by CK2 on two serine-containing clusters; involved in cell cycle regulation activity.|||Regulator of p53/TP53 stability and function. Inhibits MDM2-mediated degradation of p53/TP53 possibly by cooperating in part with TXNIP. May be involved transcriptional regulation. In vitro has intrinsic transactivation activity enhanced by EP300. May be a transcriptional activator required for the expression of glycolytic genes (By similarity). Involved in regulation of cell cycle progression (PubMed:26711270). Proposed to disrupt Rb-E2F binding leading to transcriptional activation of E2F proteins (PubMed:19640839). The cell cycle -regulating function may depend on its RUVBL1-mediated association with the R2TP complex. May play a role in regulation of pre-mRNA splicing (By similarity). http://togogenome.org/gene/10090:Or8b41 ^@ http://purl.uniprot.org/uniprot/Q7TRD9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Spon1 ^@ http://purl.uniprot.org/uniprot/Q8VCC9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds to the central extracellular domain of APP and inhibits beta-secretase cleavage of APP.|||Cell adhesion protein that promotes the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro. May contribute to the growth and guidance of axons in both the spinal cord and the PNS (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Or7e174 ^@ http://purl.uniprot.org/uniprot/Q8VFI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bloc1s1 ^@ http://purl.uniprot.org/uniprot/O55102 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BLOC1S1 family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension (PubMed:16760431, PubMed:19546860, PubMed:21998198). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. The BORC complex is most probably associated with the cytosolic face of lysosomes, may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (By similarity).|||Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8 (PubMed:15102850). The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos (PubMed:21998198). Interacts with ATP5F1A and NDUFA9; involved in their acetylation on lysine residues (By similarity). Interacts with KXD1 (PubMed:22554196).|||Lysosome membrane|||May negatively regulate aerobic respiration through mitochondrial protein lysine-acetylation. May counteract the action of the deacetylase SIRT3 by acetylating and regulating proteins of the mitochondrial respiratory chain including ATP5F1A and NDUFA9.|||Mitochondrion intermembrane space|||Mitochondrion matrix|||cytosol http://togogenome.org/gene/10090:Hcn2 ^@ http://purl.uniprot.org/uniprot/O88703 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.|||Belongs to the potassium channel HCN family.|||Cell membrane|||Highly expressed in brain. Detected at low levels in heart, in ventricle, atrium and in sinoatrial node (SAN).|||Homotetramer. Heterotetramer with HCN1. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Forms an obligate 4:4 complex with accessory subunit PEX5L. Interacts with KCNE2.|||Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current.|||Phosphorylation at Ser-641 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Itih5 ^@ http://purl.uniprot.org/uniprot/Q8BJD1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ITIH family.|||May act as a tumor suppressor.|||Secreted http://togogenome.org/gene/10090:Sgk3 ^@ http://purl.uniprot.org/uniprot/Q9ERE3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Ser-486 by an unknown kinase (may be mTORC2 but not confirmed), transforming it into a substrate for PDPK1 which then phosphorylates it on Thr-320.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasmic vesicle|||Early endosome|||Interacts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner.|||Recycling endosome|||Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.|||Two specific sites, one in the kinase domain (Thr-320) and the other in the C-terminal regulatory region (Ser-486), need to be phosphorylated for its full activation.|||Widely expressed, predominantly in the heart, spleen and 7-day embryo. http://togogenome.org/gene/10090:Rab40c ^@ http://purl.uniprot.org/uniprot/Q8VHQ4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Component of the probable SCF-like ECS(RAB40C) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and RAB40C. Interacts with CUL5, RNF7, ELOB and ELOC (By similarity).|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Stmn1 ^@ http://purl.uniprot.org/uniprot/P54227|||http://purl.uniprot.org/uniprot/Q545B6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the stathmin family.|||Binds to two alpha/beta-tubulin heterodimers. Interacts with KIST.|||Highly expressed in the lateral nucleus of the amygdala.|||Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Phosphorylation at Ser-16 may be required for axon formation during neurogenesis (By similarity). Involved in the control of the learned and innate fear.|||Many different phosphorylated forms are observed depending on specific combinations among the sites which can be phosphorylated. MAPK is responsible for the phosphorylation of stathmin in response to NGF (Probable). Phosphorylation at Ser-16 seems to be required for neuron polarization (By similarity).|||Mice show deficits in spike-timing-dependent long-term potentiation, exhibit decreased memory in amygdala-dependent fear conditioning and fail to recognize danger in innately aversive environments.|||cytoskeleton http://togogenome.org/gene/10090:Prkcq ^@ http://purl.uniprot.org/uniprot/A6H667|||http://purl.uniprot.org/uniprot/Q02111 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylation at Thr-219 is required for targeting to the TCR and cellular function of PRKCQ upon antigen receptor ligation. Following TCR stimulation, phosphorylated at Tyr-90 and Ser-685 (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (By similarity).|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates to the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1.|||Cell membrane|||Cytoplasm|||Interacts with GLRX3 (via N-terminus). Interacts with ECT2.|||Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation (By similarity).|||Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation.|||Part of a membrane raft complex composed at least of BCL10, CARD11, MALT1 and IKBKB (By similarity). Interacts with GLRX3 (via N-terminus) (By similarity). Interacts with ECT2 (By similarity). Interacts with CCDC88A/GIV; the interaction leads to phosphorylation of CCDC88A and inhibition of its guanine nucleotide exchange factor activity (By similarity).|||T-lymphocytes and skeletal muscle.|||The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain. http://togogenome.org/gene/10090:Lamtor4 ^@ http://purl.uniprot.org/uniprot/Q8CF66 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated.|||Belongs to the LAMTOR4 family.|||Lysosome|||Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer. The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability. The Ragulator complex interacts with SLC38A9; the probable amino acid sensor. Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator.|||Phosphorylation at Ser-67 by PKA inhibits Ragulator complex assembly. http://togogenome.org/gene/10090:Adh1 ^@ http://purl.uniprot.org/uniprot/P00329|||http://purl.uniprot.org/uniprot/Q3UKA4 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family.|||Belongs to the zinc-containing alcohol dehydrogenase family. Class-I subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Cytoplasm|||Dimer of identical or non-identical chains of three types (A, B, C), which are coded by 3 separate genes at different loci.|||Expressed at high levels in the liver, small intestine and eye, at moderate levels in kidney, ovary and uterus, and at low levels in the spinal cord, thymus, heart, stomach mucosa, skin and testis. http://togogenome.org/gene/10090:Gpr176 ^@ http://purl.uniprot.org/uniprot/Q80WT4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice exhibit a significantly shorter circadian period.|||Expressed mainly in the brain, with prominent expression in the SCN (at protein level) (PubMed:26882873).|||Fluctuates in a circadian fashion, with highest level in night and lowest in the morning (at protein level).|||Orphan receptor involved in normal circadian rhythm behavior (PubMed:26882873). Acts through the G-protein subclass G(z)-alpha and has an agonist-independent basal activity to repress cAMP production (PubMed:26882873). http://togogenome.org/gene/10090:Ccdc68 ^@ http://purl.uniprot.org/uniprot/Q8BVC4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells (PubMed:28422092). Together with CCDC120, cooperate with subdistal appendage components ODF2, NIN and CEP170 for hierarchical subdistal appendage assembly (PubMed:28422092).|||Interacts with CEP170.|||centriole http://togogenome.org/gene/10090:Tmem252 ^@ http://purl.uniprot.org/uniprot/Q8C353 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ncl ^@ http://purl.uniprot.org/uniprot/P09405 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in B-cells that have been induced to switch to various Ig isotypes.|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Component of the SWAP complex that consists of NPM1, NCL/nucleolin, PARP1 and SWAP70 (PubMed:9642267). Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin (By similarity). Interacts with AICDA (PubMed:21518874). Interacts with APTX (By similarity). Interacts with C1QBP (By similarity). Interacts with ERBB4 (By similarity). Interacts (via C-terminus) with FMR1 isoform 6 (via N-terminus) (By similarity). Interacts with GZF1; this interaction is important for nucleolar localization of GZF1 (By similarity). Interacts with NSUN2 (By similarity). Interacts with NVL (PubMed:21474449). Interacts (via N-terminus domain) with SETX (By similarity). Interacts (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains) with TERT; the interaction is important for nucleolar localization of TERT (By similarity). Interacts with WDR46 (By similarity). Interacts with ZFP36 (By similarity). Interacts with LRRC34 (PubMed:24991885). Interacts with RRP1B (By similarity). Interacts with HNRNPU; this interaction occurs during mitosis (By similarity). Interacts with RIOK1; RIOK1 recruits NCL to PRMT5 for symmetrically methylation (By similarity). Interacts with ZBTB7B (PubMed:28784777). Interacts with MDK; this interaction promotes NCL clustering and lateral movements of this complex into lipid rafts leading to MDK internalization (By similarity). Interacts with HDGF (By similarity). Interacts with ALKBH2.|||Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats (By similarity).|||Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group.|||Symmetrically methylated by PRMT5.|||nucleolus http://togogenome.org/gene/10090:Dguok ^@ http://purl.uniprot.org/uniprot/Q504N4|||http://purl.uniprot.org/uniprot/Q9QX60 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DCK/DGK family.|||Cytoplasm|||Homodimer.|||Mitochondrion|||Phosphorylates deoxyguanosine and deoxyadenosine in the mitochondrial matrix, with the highest efficiency for deoxyguanosine (PubMed:10455141). In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on DGUOK and TK2. Phosphorylates certain nucleoside analogs (PubMed:10455141). Widely used as target of antiviral and chemotherapeutic agents.|||Spleen and thymus. Expressed at much lower levels in the brain and liver. http://togogenome.org/gene/10090:Or51k2 ^@ http://purl.uniprot.org/uniprot/Q8VF02 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tas2r143 ^@ http://purl.uniprot.org/uniprot/Q7TQB9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Ttc38 ^@ http://purl.uniprot.org/uniprot/A3KMP2 ^@ Similarity ^@ Belongs to the TTC38 family. http://togogenome.org/gene/10090:Klri1 ^@ http://purl.uniprot.org/uniprot/B2KG20 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases leading to down-regulation of cell activation.|||Expressed in natural killer (NK) cells.|||Heterodimer with KLRE1. Interacts with PTPN6.|||Lectin-like receptor for natural killer (NK) cells. Heterodimer formation with KLRE1 mediates inhibition of NK cell cytolytic activity. http://togogenome.org/gene/10090:Mcm10 ^@ http://purl.uniprot.org/uniprot/Q0VBD2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. Additionally, plays a role in preventing DNA damage during replication. Key effector of the RBBP6 and ZBTB38-mediated regulation of DNA-replication and common fragile sites stability; acts as a direct target of transcriptional repression by ZBTB38 (By similarity).|||Belongs to the MCM10 family.|||Each zinc finger-like domain binds a zinc ion and is involved in both ssDNA and dsDNA binding, as is the OB-fold domain.|||Nucleus|||Self-associates (By similarity). Interacts with ORC2. May interact with MCM2 and MCM6. Interacts with the DNA polymerase alpha subunit POLA1. Interacts with RECQL4; this interaction regulates RECQL4 unwinding activity. Interacts with WDHD1 (By similarity).|||The N-terminal domain mediates homodimerization. http://togogenome.org/gene/10090:Mapk1ip1l ^@ http://purl.uniprot.org/uniprot/Q8BH93 ^@ Similarity ^@ Belongs to the MISS family. http://togogenome.org/gene/10090:Sdcbp ^@ http://purl.uniprot.org/uniprot/O08992 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Endoplasmic reticulum membrane|||Melanosome|||Membrane raft|||Monomer and homodimer. Interacts with SDC1, SDC2, SDC3, SDC4, NRXN2, EPHA7, EPHB1, NF2 isoform 1, TGFA, IL5RA, NFASC, SDCBP2 and PTPRJ (By similarity). Interacts with PDCD6IP (PubMed:22660413). Forms a complex with PDCD6IP and SDC2 (By similarity). Interacts (via C-terminus) with TGFBR1 (By similarity). Binds to FZD7; this interaction is increased by inositol trisphosphate (IP3) (By similarity). Interacts with SMO (PubMed:25644602).|||Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis. Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1. In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (By similarity). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA). May also play a role in vesicular trafficking. Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (By similarity).|||Nucleus|||Phosphorylated on tyrosine residues.|||adherens junction|||cytoskeleton|||cytosol|||extracellular exosome|||focal adhesion http://togogenome.org/gene/10090:Cnksr1 ^@ http://purl.uniprot.org/uniprot/A2A9K7 ^@ Similarity ^@ Belongs to the CNKSR family. http://togogenome.org/gene/10090:Fabp3 ^@ http://purl.uniprot.org/uniprot/P11404|||http://purl.uniprot.org/uniprot/Q5EBJ0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters.|||Forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior. http://togogenome.org/gene/10090:Lyset ^@ http://purl.uniprot.org/uniprot/Q8BH26 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LYSET family.|||Golgi apparatus membrane|||Interacts with GNPTAB; this interaction is important for proper localization of GNPTAB in Golgi stacks. Interacts with MBTPS1.|||LYSET knockout mice display increased lysosomal enzyme serum levels and storage materials in lysosomes. In addition, LYSET KO embryonic fibroblasts are resistant to infection by EBOV glycoprotein (VSV-EBOV).|||Required for mannose-6-phosphate-dependent trafficking of lysosomal enzymes. LYSET bridges GlcNAc-1-phosphate transferase (GNPTAB), to the membrane-bound transcription factor site-1 protease (MBTPS1), thus allowing proteolytic activation of the GNPTAB. GNPTAB is involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. LYSET is thus an essential factor for maturation and delivery of lysosomal hydrolases (By similarity). Plays an essential function for cells that depend on lysosomal catabolism to generate nutrients (PubMed:36074821). http://togogenome.org/gene/10090:Ces2g ^@ http://purl.uniprot.org/uniprot/E9PV38 ^@ Similarity ^@ Belongs to the type-B carboxylesterase/lipase family. http://togogenome.org/gene/10090:Ccdc87 ^@ http://purl.uniprot.org/uniprot/Q8CDL9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the CCDC87 family.|||Detected from postnatal day 14 onwards. Maintained at high levels through to adulthood.|||No gross phenotype. Males have significantly reduced fertility. Testis weight, testis histology and sperm counts are normal. Approximately 25% of sperm have morphological defects in the sperm head and sperm nucleus, while morphology of the sperm flagellum appears normal. Capacitation-induced sperm motility is initially slightly reduced but then recovers. Frequency of both spontaenous and P4-induced acrosome reactions are significantly reduced. In an in-vitro fertilization assay, spermatozoa are able to bind and penetrate the oocyte perivitelline space but fertilizing capacity is severely impaired.|||Plays a role in spermatogenesis, where it is important for normal sperm head morphology. Also required for the acrosome reaction and thus normal male fertility.|||Specifically expressed in testis (at protein level). Not detected in other tissues tested (at protein level). In the testis, localizes to pachytene spermatocytes and spermatids. http://togogenome.org/gene/10090:Dcaf13 ^@ http://purl.uniprot.org/uniprot/Q6PAC3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat DCAF13/WDSOF1 family.|||Component of the DCX(DCAF13) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF13 and RBX1. Interacts (via WD40 domain) with DDB1 (PubMed:30111536, PubMed:31492966, PubMed:35178836). Interacts with ESR1 and LATS1 (By similarity).|||In embryo, expressed as early as the four-cell stage and continue to accumulate in morulae and blastocysts (at protein level) (PubMed:30111536). Expressed in growing oocytes with the nonsurrounded nucleolus configuration, reaches a peak in oocytes within pre-antral and early antral follicles and nearly disappears in the fully grown oocyte with the surrounded nucleolus configuration (PubMed:30283081).|||Knockout embryos are arrested at the eight- to sixteen-cell stage before compaction causing preimplantation-stage mortality (PubMed:30111536). Mutant embryos are morphologically normal up to the eight-cell stage but they do not compact, fail to develop into blastocysts and die at the morula stage (PubMed:30111536). Oocyte-specific knockout females are infertile (PubMed:30283081, PubMed:31000741). The ovaries of 8-week-old females are significantly smaller than those of wild-type females and are devoid of follicles containing more than two layers of granulosa cells and corpora lutea. The ovaries are deficient in follicles beyond the secondary follicle stage and contained fewer primordial follicles than the control ovaries. At 5 months of age, oocytes disappear in the ovaries and only primordial and primary follicles are seen in the mutant ovaries (PubMed:30283081). Oocyte-specific maternal knockout embryos display arrest at the two-cell stage (PubMed:31000741). Conditional knockout females under the control of progesterone receptor fail to undergo decidualization (PubMed:35932979).|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity). Participates in the 18S rRNA processing in growing oocytes, being essential for oocyte nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) transition (PubMed:30283081).|||Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that plays a key role in embryo preimplantation and is required for normal meiotic cycle progression in oocytes (PubMed:30111536, PubMed:31492966). Acts as a maternal factor that regulates oocyte and zygotic chromatin tightness during maternal to zygotic transition (PubMed:31000741). Also involved in the transformation of the endometrium into the decidua, known as decidualization, providing a solid foundation for implantation of blastocysts (PubMed:35932979). Recognizes the histone methyltransferases SUV39H1 and SUV39H2 and directs them to polyubiquitination and proteasomal degradation, which facilitates the H3K9me3 removal and early zygotic gene expression, essential steps for progressive genome reprogramming and the establishment of pluripotency during preimplantation embryonic development (PubMed:30111536). Supports the spindle assembly and chromosome condensation during oocyte meiotic division by targeting the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation (PubMed:31492966). Targets PMP22 for polyubiquitination and proteasomal degradation (PubMed:35178836).|||Uniformly distributed in trophectoderm cells and inner cells mass in blastocyst embryos (PubMed:30111536). Expressed in oocytes as early as the primordial follicle stage (PubMed:30283081). Endometrial expression increases during decidualization and is highly expressed in decidua (PubMed:35932979).|||nucleolus http://togogenome.org/gene/10090:Rfc4 ^@ http://purl.uniprot.org/uniprot/Q99J62 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the activator 1 small subunits family.|||Despite of the presence of a putative ATP-binding motif, this protein does not bind ATP.|||Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA (By similarity). Interacts with CNTD1; this interaction facilitates crossover formation (PubMed:32640224).|||Nucleus|||The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. This subunit may be involved in the elongation of the multiprimed DNA template (By similarity). http://togogenome.org/gene/10090:Prr16 ^@ http://purl.uniprot.org/uniprot/A3KMN5 ^@ Function|||Miscellaneous ^@ Overexpression causes embryonic lethality. Conditional overexpression leads to increased cell size (PubMed:24656129).|||Regulator of cell size that promotes cell size increase independently of mTOR and Hippo signaling pathways. Acts by stimulating the translation of specific mRNAs, including those encoding proteins affecting mitochondrial functions. Increases mitochondrial mass and respiration (Probable). http://togogenome.org/gene/10090:Or51b6 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSF4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Susd2 ^@ http://purl.uniprot.org/uniprot/Q9DBX3 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||May be a cytokine receptor for GPR15LG. May be a tumor suppressor; together with GPR15LG has a growth inhibitory effect on colon cancer cells which includes G1 cell cycle arrest (By similarity). May play a role in breast tumorigenesis (PubMed:23131994). http://togogenome.org/gene/10090:Clpb ^@ http://purl.uniprot.org/uniprot/Q60649 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ClpA/ClpB family.|||Despite its gene name, this protein differs in domain structure from bacterial clpB. Bacterial clpB contains two AAA modules, one in the N-terminal part of the protein and one in the C-terminal part, separated by a coiled coil, while vertebrate CLPB contains a single C-terminal AAA region and an N-terminal ANK repeat region which is absent from bacterial clpB.|||Disaggregase activity is inhibited by ADP.|||Functions as a regulatory ATPase and participates in secretion/protein trafficking process. Has ATP-dependent protein disaggregase activity and is required to maintain the solubility of key mitochondrial proteins. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6. Plays a role in granulocyte differentiation.|||Homododecamer when substrate-bound; the homododecamer consists of 2 homohexamers stacked head-to-head via ANK repeat-mediated interactions. The active substrate-bound form is likely to exist in a dynamic equilibrium between homohexamers and homododecamers. Homotetradecamer in the unbound state which is remodeled upon substrate binding into the homododecamer. Interacts with PHB and PHB2. Interacts with MAVS; the interaction is enhanced by Sendai virus infection.|||Mitochondrion intermembrane space|||Proteolytically cleaved by protease PARL. ATP-dependent protein disaggregase activity is stimulated by PARL-mediated cleavage of the N-terminal autoinhibitory peptide.|||The ankyrin-repeat region is necessary for ATP-dependent protein disaggregase activity. It plays an important role in stabilizing the substrate-bound homododecamer by mediating contacts between the two homohexamers.|||Widely expressed, with highest levels in testis. Also expressed in heart, skeletal muscle and kidney. http://togogenome.org/gene/10090:Ahcyl ^@ http://purl.uniprot.org/uniprot/P50247|||http://purl.uniprot.org/uniprot/Q3TF14 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenosylhomocysteinase family.|||Binds 1 NAD(+) per subunit.|||Catalyzes the hydrolysis of S-adenosyl-L-homocysteine to form adenosine and homocysteine (PubMed:7657650). Binds copper ions (PubMed:7657650).|||Cytoplasm|||Endoplasmic reticulum|||Homotetramer. Interaction with AHCYL1 (By similarity).|||Melanosome|||Nucleus http://togogenome.org/gene/10090:Tmem63b ^@ http://purl.uniprot.org/uniprot/Q3TWI9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as an osmosensitive calcium-permeable cation channel (PubMed:27045885, PubMed:31243992). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938).|||Belongs to the CSC1 (TC 1.A.17) family.|||Cell membrane http://togogenome.org/gene/10090:Zfp418 ^@ http://purl.uniprot.org/uniprot/Q8BFS8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Transcriptional repressor (By similarity). May play a role as regulator of the ubiquitin-proteasome system and autophagy-lysosomal pathway (PubMed:33249983). http://togogenome.org/gene/10090:Pheta2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Z2|||http://purl.uniprot.org/uniprot/Q14B98 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sesquipedalian family.|||Early endosome|||Forms homodimers and heterodimers with PHETA. Interacts with OCRL and INPP5B.|||Forms homodimers and heterodimers with PHETA1. Interacts with OCRL and INPP5B.|||Plays a role in endocytic trafficking. Required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane.|||Recycling endosome|||The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B.|||Was named after 'sesquipedalian', an unnecessarily long description of a simple thing.|||clathrin-coated vesicle|||trans-Golgi network http://togogenome.org/gene/10090:Svs5 ^@ http://purl.uniprot.org/uniprot/P30933|||http://purl.uniprot.org/uniprot/Q545K7 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SVP2/SVP5/SVP6 family.|||By testosterone.|||Testis.|||extracellular space http://togogenome.org/gene/10090:Or1e32 ^@ http://purl.uniprot.org/uniprot/Q7TRX6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adam9 ^@ http://purl.uniprot.org/uniprot/A0A140LHU0|||http://purl.uniprot.org/uniprot/Q3U1W3|||http://purl.uniprot.org/uniprot/Q3UG15|||http://purl.uniprot.org/uniprot/Q61072 ^@ Activity Regulation|||Caution|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Cell membrane|||Deficient mice appear to develop normally, are viable and fertile, and do not have any major pathological phenotypes (PubMed:11839819). In adulthood, 20 months after birth, mice display progressive retinal degeneration, disorganized retinal layers and a degenerate retinal pigment epithelium (PubMed:19409519).|||Interacts with SH3GL2 and SNX9 through its cytoplasmic tail (PubMed:10531379). Interacts with ITGA6 (PubMed:10825303).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Metalloprotease that cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5 (PubMed:9920899, PubMed:19273593). May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins (PubMed:10825303).|||Phosphorylation is induced in vitro by phorbol-12-myristate-13-acetate (PMA) (PubMed:9920899).|||Proteolytically cleaved in the trans-Golgi network before it reaches the plasma membrane to generate a mature protein. The removal of the pro-domain occurs via cleavage at two different sites. Processed most likely by a pro-protein convertase such as furin, at the boundary between the pro-domain and the catalytic domain. An additional upstream cleavage pro-protein convertase site (Arg-56/Glu-57) has an important role in the activation of ADAM9.|||Synthesized as an inactive form which is proteolytically cleaved to generate an active enzyme. Processing at the upstream site is particularly important for activation of the proenzyme, whereas processing at the boundary between the pro-domain and the catalytic domain does not appear to be essential (PubMed:25795784). Inhibited by hydroxamic acid-based inhibitors (PubMed:9920899). http://togogenome.org/gene/10090:Aoc1 ^@ http://purl.uniprot.org/uniprot/E9PYN9|||http://purl.uniprot.org/uniprot/Q3UKB9 ^@ Cofactor|||PTM|||Similarity ^@ Belongs to the copper/topaquinone oxidase family.|||Contains 1 topaquinone per subunit.|||Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. http://togogenome.org/gene/10090:Galnt18 ^@ http://purl.uniprot.org/uniprot/Q8K1B9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor.|||Golgi apparatus membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Rhox11 ^@ http://purl.uniprot.org/uniprot/Q810N8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Fcrl5 ^@ http://purl.uniprot.org/uniprot/Q68SN8 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with PTPN6, PTPN11, SYK and ZAP70.|||It is uncertain whether Met-1 or Met-14 is the initiator.|||Mating of knockout (KO) female and wild-type (WT) male results in 30% KO/WT pairs without fertilization output.|||May play a role in fertilization.|||Phosphorylated on cytoplasmic tyrosines; required for interaction with protein tyrosine phosphatases and protein tyrosine kinases.|||Preferentially expressed in marginal zone B cells. http://togogenome.org/gene/10090:Shisa2 ^@ http://purl.uniprot.org/uniprot/Q8QZV2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the shisa family.|||Endoplasmic reticulum membrane|||Expressed at 5.5 dpc in the distal visceral endoderm. Expression increases at 6.5 dpc in the most anterior part of the visceral endoderm. At 7.0 dpc expression spreads over the anterior visceral endoderm and occurs in the anterior ectoderm. At 7.75 dpc expressed in the definitive anterior endoderm, anterior mesoderm and anterior neuroectoderm. At 8.25 dpc, when the headfold is formed, expressed in the forebrain, foregut and in segmented somites. At 12.5 dpc, expressed in cerebrum cortex, lateral ganglionic eminences, preoptic area neuroepithelium, hypothalamus, ventral part of otic placode including adjacent mesenchyme, a part of the tongue, endocardial cushion around aortic valve, myotome and muscle primordia.|||Mice exhibit no defects in head development. Mice are live-born. About one-third of the homozygous mutants were normal and fertile and about two-thirds were dwarf. Reduction in weight gain became apparent at the postnatal third week; about half of the dwarf mice subsequently resumed the weight increase, although they remained dwarf; the other died within a month after birth.|||Plays an essential role in the maturation of presomitic mesoderm cells by individual attenuation of both FGF and WNT signaling. http://togogenome.org/gene/10090:Meis2 ^@ http://purl.uniprot.org/uniprot/A0A0A7EPH8|||http://purl.uniprot.org/uniprot/B1AWK4|||http://purl.uniprot.org/uniprot/P97367|||http://purl.uniprot.org/uniprot/Q3TY73|||http://purl.uniprot.org/uniprot/Q3TYM2|||http://purl.uniprot.org/uniprot/Q3UJ35|||http://purl.uniprot.org/uniprot/Q6GU28 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TALE/MEIS homeobox family.|||By retinoic acid.|||Displays spatially restricted expression patterns in the developing nervous system, limbs, face, and in various viscera. In adult, it is mainly expressed in the brain and female genital tract, with a different distribution of the alternative splice forms in these organs. Lower expression in lung and only basal level in heart, liver, kidney, spleen, and testis. Expressed in pancreatic islets (beta-cells only) (PubMed:21059917).|||Expressed at high levels in all stages of embryonic development analyzed (7 days to 17 days). First detected around 10.5 dpc in the developing ventrolateral telencephalon. Is found at moderate levels throughout the ventricle zone (VZ) of the entire telencephalon with the exception of the ventro- and dorso-medial regions. The highest expression is detected in the subventricular zone (SVZ) of the lateral ganglionic eminence (LGE) and developing striatum. By 16.5 dpc, also found in the cortical plate. Also expressed at high levels in the caudal ganglionic eminence (CGE) and amygdala. Expression in the telencephalon remains unchanged at birth and into adulthood.|||Involved in transcriptional regulation. Binds to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of PBX and HOX proteins and thought to have a role in stabilization of the homeoprotein-DNA complex. Isoform Meis2B is required for the activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element; MEIS2 is not involved in complex DNA-binding. Probably in complex with PBX1, is involved in transcriptional regulation by KLF4. Isoforms Meis2B and Meis2D can bind to a EPHA8 promoter sequence containing the DNA motif 5'-CGGTCA-3'; in cooperation with a PBX protein (such as PBX2) is proposed to be involved in the transcriptional activation of EPHA8 in the developing midbrain. May be involved in regulation of myeloid differentiation. Can bind to the DNA sequence 5'-TGACAG-3'in the activator ACT sequence of the D(1A) dopamine receptor (DRD1) promoter and activate DRD1 transcription.|||Monomer and homodimer. Heterodimer with HOXB13 (By similarity). Isoform Meis2A interacts with TLX1. Isoform Meis2B interacts with HOXA13 and PBX1 isoform PBX1b. Isoform Meis2D interacts with SP1, SP3 and KLF4. Isoform Meis2D interacts with PBX1 isoform PBX1a; the interaction partially relieves MEIS2 autoinhibition. Isoform Meis2B is part of a PDX1:PBX1b:MEIS2b complex; Meis2B is recruited by PBX1b and can be replaced by isoform Meis2D in a small fraction of complexes. Can form trimeric complexes including HOXB8 and PBX2 or PBX3.|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Ap1g2 ^@ http://purl.uniprot.org/uniprot/O88512|||http://purl.uniprot.org/uniprot/Q3U9D1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adaptor complexes large subunit family.|||Cytoplasmic vesicle membrane|||Endosome membrane|||Golgi apparatus membrane|||May function in protein sorting in late endosomes or multivesucular bodies (MVBs). Involved in MVB-assisted maturation of hepatitis B virus (HBV).|||May interact with AP1S1/Sigma1A-adaptin and AP1S2/Sigma1B-adaptin (By similarity). Probably does not interact with APB1 (By similarity). Interacts (via GAE domain) with RABEP1, NECAP1, CLINT1 and AFTPH/aftiphilin (By similarity). Interacts with HBV major surface antigen L. Interacts with HBV core protein C in a ubiquitin-dependent manner. Binds ubiquitin.|||Widely expressed. http://togogenome.org/gene/10090:Arl4a ^@ http://purl.uniprot.org/uniprot/P61213 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Arf family.|||Cell membrane|||Cytoplasm|||Expressed strongly in embryo at 7 dpc. Expressed slightly in embryo at 11, 15 and 17 dpc.|||Expressed strongly in testis and liver. Expressed slightly in heart, spleen, lung and kidney.|||Interacts with CYTH2. Interacts with KPNA2; the interaction is direct. Does not interact with ARL4A (By similarity).|||Myristoylated.|||Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Recruits CYTH1, CYTH2, CYTH3 and CYTH4 to the plasma membrane in GDP-bound form (By similarity).|||nucleolus http://togogenome.org/gene/10090:Hoxc12 ^@ http://purl.uniprot.org/uniprot/Q8K5B8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Odf2 ^@ http://purl.uniprot.org/uniprot/A3KGV1|||http://purl.uniprot.org/uniprot/A3KGW0|||http://purl.uniprot.org/uniprot/Q3UFG2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ODF2 family.|||Null mutations in F9 embryonic carcinoma cells eliminated distal/subdistal appendages and prevented primary cilium formation. Loss of ODF2 also disrupted two mother centriole-specific NIN dots, while leaving one dot on the proximal end of mother and daughter centrioles.|||Seems to be a major component of sperm tail outer dense fibers (ODF). ODFs are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. May have a modulating influence on sperm motility. Functions as a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles. Component of the centrosome matrix required for the localization of PLK1 and NIN to the centrosomes. Required for the formation and/or maintenance of normal CETN1 assembly (By similarity).|||Self-associates. Associates with microtubules and forms a fibrillar structure partially linked to the microtubule network. Interacts via its C-terminus with PLK1 (By similarity). Interacts with ODF1 (PubMed:9045620). Interacts with MARK4; the interaction is required for localization of ODF2 to centrioles (By similarity). Interacts with TSSK4 (PubMed:25361759, PubMed:26961893). Interacts with AKNA (PubMed:30787442). Interacts with CFAP58 (PubMed:31904090).|||Testis-specific (at protein level) (PubMed:9045620, PubMed:27682589, PubMed:31904090). Expressed in spermatids at tubular stage V of the spermatogenic cycle (PubMed:9740324). Highly expressed in the cytoplasm of elongating spermatids (tubular stages X/XI) (PubMed:9740324). In step 14/15 spermatids of tubular stage III/IV low expression detected (PubMed:9740324). No expression detected in other testicular cells as well as the early round of spermatids (PubMed:9740324).|||Tyrosine phosphorylated (By similarity). Phosphorylated on Ser-95 by TSSK4 (PubMed:26961893).|||centriole|||centrosome|||cilium|||flagellum|||spindle pole http://togogenome.org/gene/10090:Ahdc1 ^@ http://purl.uniprot.org/uniprot/Q6PAL7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Chromosome|||Lethality; mice do not survive past birth (PubMed:35585237). Mutant mice show developmental patterning defects affecting craniofacial structure, abdominal wall closure and epidermal stratification (PubMed:35585237).|||Nucleus|||Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis (PubMed:35585237). Directly binds promoter and enhancer regions and acts by maintaining local enhancer-promoter chromatin architecture (By similarity). Interacts with many sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes that wire surface ectoderm stratification (By similarity). http://togogenome.org/gene/10090:Defa40 ^@ http://purl.uniprot.org/uniprot/L7N231 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Cts6 ^@ http://purl.uniprot.org/uniprot/Q9ET52 ^@ Similarity ^@ Belongs to the peptidase C1 family. http://togogenome.org/gene/10090:Dlk2 ^@ http://purl.uniprot.org/uniprot/Q8K1E3 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Absent from liver after birth, but increases around postnatal day 16.|||Detected in a number of tissues including lung, brain, adrenal gland, testis, adult liver, placenta, ovary and thymus. Not detected in fetal liver or in adult spleen, muscle and heart.|||Membrane|||Regulates adipogenesis.|||Splice sites are non-canonical. http://togogenome.org/gene/10090:Ino80d ^@ http://purl.uniprot.org/uniprot/B1AT32|||http://purl.uniprot.org/uniprot/Q66JY2 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the INO80D family.|||Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80.|||Contaminating sequence. Potential poly-A sequence.|||Nucleus|||Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. http://togogenome.org/gene/10090:Il12b ^@ http://purl.uniprot.org/uniprot/P43432|||http://purl.uniprot.org/uniprot/Q3ZAX5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of pro-inflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.|||Belongs to the IL-12B family.|||Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.|||Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12.|||Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12. Heterodimer with IL23A; disulfide-linked. The heterodimer is known as interleukin IL-23. Also secreted as a monomer. Interacts with NBR1; this interaction promotes IL-12 secretion (PubMed:34374750).|||Secreted http://togogenome.org/gene/10090:Cfap54 ^@ http://purl.uniprot.org/uniprot/Q8C6S9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CFAP54 family.|||Deficient mice shown hydrocephalus, male infertility, and accumulation of mucus in the sinus cavity. The male infertility is due to severe defects in spermatid flagellar formation.|||Expressed at high level in the testis and at a low level in the lung and brain.|||Required for assembly and function of cilia and flagella (PubMed:26224312).|||cilium axoneme http://togogenome.org/gene/10090:Mpp7 ^@ http://purl.uniprot.org/uniprot/G5E8S8|||http://purl.uniprot.org/uniprot/Q8BVD5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an important adapter that promotes epithelial cell polarity and tight junction formation via its interaction with DLG1. Involved in the assembly of protein complexes at sites of cell-cell contact (By similarity).|||Belongs to the MAGUK family.|||Cytoplasm|||Heterodimer; able to heterodimerize via its C-terminal L27 domain with LIN7A, LIN7B and LIN7C. Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C). Interacts with DLG1 via its N-terminal L27 domain. Interacts with PALS1 and PATJ (By similarity).|||Lateral cell membrane|||Membrane|||Phosphorylated by aPKC which promotes dissociation from the cell cortex.|||The phospho-regulated basic and hydrophobic (PRBH) motif is sufficient and important for interaction with phospholipids permitting cortical localization (By similarity). Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane (By similarity).|||adherens junction|||cell cortex|||tight junction http://togogenome.org/gene/10090:Clec4f ^@ http://purl.uniprot.org/uniprot/P70194 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Kupffer cells.|||Membrane|||Receptor with an affinity for galactose and fucose. Could be involved in endocytosis. http://togogenome.org/gene/10090:H2al1a ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:Asphd1 ^@ http://purl.uniprot.org/uniprot/Q2TA57 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the aspartyl/asparaginyl beta-hydroxylase family.|||Membrane http://togogenome.org/gene/10090:Anapc15 ^@ http://purl.uniprot.org/uniprot/G5E8M3|||http://purl.uniprot.org/uniprot/H3BIU1|||http://purl.uniprot.org/uniprot/P60007|||http://purl.uniprot.org/uniprot/Q9D3A0 ^@ Caution|||Function|||Similarity|||Subunit ^@ Belongs to the APC15 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. In the complex, plays a role in the release of the mitotic checkpoint complex (MCC) from the APC/C: not required for APC/C activity itself, but promotes the turnover of CDC20 and MCC on the APC/C, thereby participating in the responsiveness of the spindle assembly checkpoint. Also required for degradation of CDC20 (By similarity).|||It is uncertain whether Met-1 or Met-12 is the initiator.|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. http://togogenome.org/gene/10090:F11 ^@ http://purl.uniprot.org/uniprot/Q91Y47 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by factor XIIa (or XII), which cleaves each polypeptide after Arg-389 into the light chain, which contains the active site, and the heavy chain, which associates with high molecular weight (HMW) kininogen.|||Belongs to the peptidase S1 family. Plasma kallikrein subfamily.|||Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.|||Homodimer; disulfide-linked. Forms a heterodimer with SERPINA5. After activation the heavy and light chains are also linked by a disulfide bond (By similarity).|||Inhibited by SERPINA5.|||N-glycosylated on both chains. N-glycosylated sites mainly consist of nonfucosylated sialylated biantennary (in high abundance) and/or triantennary (in low abundance) complex structures.|||Secreted http://togogenome.org/gene/10090:Shroom2 ^@ http://purl.uniprot.org/uniprot/A2ALU4|||http://purl.uniprot.org/uniprot/A7TU71|||http://purl.uniprot.org/uniprot/Q8C7N5 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the shroom family.|||Interacts with F-actin.|||May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution.|||Present in kidney tubules and in the vasculature of many tissues (at protein level).|||Present in the vasculature and in multiple epithelial populations at 10.5 dpc. Present in the cell junctions of the retinal pigmented epithelium at 15.5 dpc (at protein level).|||The ASD1 domain mediates F-actin binding.|||cytoskeleton|||tight junction http://togogenome.org/gene/10090:Tbl1x ^@ http://purl.uniprot.org/uniprot/Q9QXE7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat EBI family.|||Expressed in the cochlea.|||F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (By similarity).|||Homotetramer; dimer of dimers (By similarity). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with GPS2 (when sumoylated); leading to protect GPS2 against degradation by the proteasome (PubMed:26070566). Probably part of other corepressor complexes, that do not contain NCOR1 and NCOR2. Interacts with histones H2B, H3a and H4 (By similarity). Interacts with MECP2; recruits TBL1X to the heterochromatin foci (PubMed:28348241). Interacts with USP44 (By similarity).|||Nucleus|||The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes. http://togogenome.org/gene/10090:Ubac1 ^@ http://purl.uniprot.org/uniprot/Q8VDI7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the KPC complex composed of RNF123/KPC1 and UBAC1/KPC2. Interacts (via ubiquitin-like domain) with RNF123. Interacts (via ubiquitin-like and UBA domains) with the proteasome via its N-terminal domain.|||Cytoplasm|||Non-catalytic component of the KPC complex, a E3 ubiquitin-protein ligase complex that mediates polyubiquitination of target proteins, such as CDKN1B and NFKB1. The KPC complex catalyzes polyubiquitination and proteasome-mediated degradation of CDKN1B during G1 phase of the cell cycle. The KPC complex also acts as a key regulator of the NF-kappa-B signaling by promoting maturation of the NFKB1 component of NF-kappa-B by catalyzing ubiquitination of the NFKB1 p105 precursor. Within the KPC complex, UBAC1 acts as an adapter that promotes the transfer of target proteins that have been polyubiquitinated by RNF123/KPC1 to the 26S proteasome.|||The UBA domains recognize and bind polyubiquitinated proteins. http://togogenome.org/gene/10090:Shisa8 ^@ http://purl.uniprot.org/uniprot/J3QNX5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shisa family.|||Brain-specific. Highly expressed in cerebellum and olfactory bulb.|||Interacts with AMPAR subunits GRIA1 and GRIA2.|||May regulate trafficking and current kinetics of AMPA-type glutamate receptor (AMPAR) at synapses.|||Membrane|||Undetectable in the brain of 17 dpc embryos. Expressed in olfactory bulb from postnatal day 1 (P1) and then in cerebellum from postnatal day 14 (P14). http://togogenome.org/gene/10090:Prox1 ^@ http://purl.uniprot.org/uniprot/P48437 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Prospero homeodomain family.|||Expressed in a circadian manner in the liver with a peak at ZT4.|||Expressed in the young neurons of the subventricular region of the CNS, developing eye lens and pancreas. It is also found in the developing liver, heart and skeletal muscle. In the eye, expressed in the lens and retina at postnatal day 10. In the retina, localized to the inner nuclear layer. In the lens, localized to epithelial and fiber cells.|||Interacts with RORA and RORG (via AF-2 motif).|||Nucleus|||The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain (Potential). The Prospero-type homeodomain is essential for repression of RORG transcriptional activator activity (PubMed:23723244).|||Transcription factor involved in developmental processes such as cell fate determination, gene transcriptional regulation and progenitor cell regulation in a number of organs. Plays a critical role in embryonic development and functions as a key regulatory protein in neurogenesis and the development of the heart, eye lens, liver, pancreas and the lymphatic system. Involved in the regulation of the circadian rhythm. Represses: transcription of the retinoid-related orphan receptor RORG, transcriptional activator activity of RORA and RORG and the expression of RORA/G-target genes including core clock components: BMAL1, NPAS2 and CRY1 and metabolic genes: AVPR1A and ELOVL3. http://togogenome.org/gene/10090:Spesp1 ^@ http://purl.uniprot.org/uniprot/Q9D5A0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SPESP1 family.|||Glycosylated. In testis there are two predominant forms of 77- and 67-kDa and a form of 47-kDa, whereas in epididymal sperm from caput, corpus, and cauda there are two forms of 47- and 43-kDa. Testis forms contain complex carbohydrate residues. Epididymal sperm forms are N-glycosylated. Then undergoes significant glycosylation in the testis and that the majority of these glycoconjugates are removed by the time sperm reach the caput epididymis.|||Involved in fertilization ability of sperm.|||Knockout female mice are fertile, while the average number of pups that are fathered by knockout males is significantly lower than that of wild-type fathers.|||Testis specific.|||acrosome http://togogenome.org/gene/10090:Lvrn ^@ http://purl.uniprot.org/uniprot/E9QJR0 ^@ Cofactor|||Similarity ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit. http://togogenome.org/gene/10090:Ldoc1 ^@ http://purl.uniprot.org/uniprot/Q7TPY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LDOC1 family.|||Interacts with NOD2.|||May have an important role in the development and/or progression of some cancers.|||Nucleus http://togogenome.org/gene/10090:Or2ag12 ^@ http://purl.uniprot.org/uniprot/Q8VF89 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Acot8 ^@ http://purl.uniprot.org/uniprot/P58137|||http://purl.uniprot.org/uniprot/Q3U965 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:11673457). Displays no strong substrate specificity with respect to the carboxylic acid moiety of Acyl-CoAs (PubMed:11673457). Hydrolyzes medium length (C2 to C20) straight-chain, saturated and unsaturated acyl-CoAS but is inactive towards substrates with longer aliphatic chains (PubMed:11673457). Moreover, it catalyzes the hydrolysis of CoA esters of bile acids, such as choloyl-CoA and chenodeoxycholoyl-CoA and competes with bile acid CoA:amino acid N-acyltransferase (BAAT) (PubMed:11673457). Is also able to hydrolyze CoA esters of dicarboxylic acids (PubMed:16141203). It is involved in the metabolic regulation of peroxisome proliferation (By similarity).|||Constitutes about 1% of total peroxisomal protein.|||Induced in the liver, by peroxisome proliferator or fasting via the peroxisome proliferator-activated receptors (PPARs). Diurnal regulation of its expression.|||Inhibited by CoASH (IC(50)=10-15 uM). Also inhibited by cysteine-reactive agents.|||Peroxisome matrix|||Ubiquitous.|||homodimer. http://togogenome.org/gene/10090:Serhl ^@ http://purl.uniprot.org/uniprot/Q9EPB5 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily.|||Induced by passive stretch of skeletal muscle.|||Peroxisome|||Present in both unfused and recently fused myotubes, but not thereafter.|||Probable serine hydrolase. May be related to cell muscle hypertrophy.|||Ubiquitous. High protein expression in skeletal and cardiac muscle.|||perinuclear region http://togogenome.org/gene/10090:Ftmt ^@ http://purl.uniprot.org/uniprot/Q9D5H4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ferritin family.|||Catalyzes the oxidation of ferrous iron(II) to ferric iron(III) and stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation.|||Homooligomer of 24 subunits. The functional molecule is roughly spherical and contains a central cavity into which the polymeric mineral iron core is deposited (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Thbs4 ^@ http://purl.uniprot.org/uniprot/B2RTL6|||http://purl.uniprot.org/uniprot/Q9Z1T2 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of vascular inflammation and adaptive responses of the heart to pressure overload and in myocardial function and remodeling. Binds to structural extracellular matrix (ECM) proteins and modulates the ECM in response to tissue damage, contributing to cardioprotective and adaptive ECM remodeling. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors and protects myocardium from pressure overload. May contribute to spinal presynaptic hypersensitivity and neuropathic pain states after peripheral nerve injury. May play a role in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury in a NOTCH1-dependent manner.|||Belongs to the thrombospondin family.|||Endoplasmic reticulum|||Heart. Up-regulated in the heart in response to ischemic injury and pathology (at protein level). Astrocytes; expressed at high levels in subventricular zone (SVZ)-derived astrocytes and at low levels in cortical astrocytes. In response to peripheral nerve injury, significantly up-regulated in the dorsal spinal cord (at protein level).|||Homopentamer; disulfide-linked. Interacts with PTBP3 (By similarity). Interacts (via EGF-like 3; calcium-binding domain) with ATF6 and facilitates its processing, activation and nuclear translocation. Interacts with NOTCH1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||On exposure to acute pressure overload, mice exhibit a marked increase in: heart weight and fibrosis, cardiomyocyte size and number of apoptotic cells in the myocardium, deposition of extracellular matrix (ECM) and levels of interstitial collagens. The increased ECM deposition is accompanied by changes in functional parameters of the heart and decreased vessel density. Mice also show defective induction of the ER stress response in the heart. Do not exhibit peripheral nerve injury-induced behavioral hypersensitivities such as thermal/mechanical hyperalgesia and tactile allodynia but show severe defects in cortical-injury-induced subventricular zone astrogenesis.|||Sarcoplasmic reticulum|||Secreted|||extracellular matrix|||extracellular space http://togogenome.org/gene/10090:2810004N23Rik ^@ http://purl.uniprot.org/uniprot/Q8CIL4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Prevents helicase DHX37 to be recruited before post-A1 state.|||nucleolus http://togogenome.org/gene/10090:Sat2 ^@ http://purl.uniprot.org/uniprot/Q6P8J2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family.|||Catalyzes the N-acetylation of the amino acid thialysine (S-(2-aminoethyl)-L-cysteine), a L-lysine analog with the 4-methylene group substituted with a sulfur. May also catalyze acetylation of polyamines, such as norspermidine, spermidine or spermine. However, ability to acetylate polyamines is weak, suggesting that it does not act as a diamine acetyltransferase in vivo.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Acsl3 ^@ http://purl.uniprot.org/uniprot/Q9CZW4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (By similarity). ACSL3 is required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins) (By similarity). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity (By similarity).|||Belongs to the ATP-dependent AMP-binding enzyme family.|||Endoplasmic reticulum membrane|||High expression in ob/ob mice (obese) and mice fed at high sucrose diet.|||Microsome membrane|||Mitochondrion outer membrane|||Peroxisome membrane http://togogenome.org/gene/10090:Mtmr14 ^@ http://purl.uniprot.org/uniprot/Q8VEL2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||In C2C12 cell line, increased expression during myotube formation and differentiation in culture.|||Lipid phosphatase which efficiently dephosphorylates phosphatidylinositol 3-phosphate (PtdIns3P) and PtdIns(3,5)P2; inactive toward PtdIns4P, PtdIns(3,4)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P3. http://togogenome.org/gene/10090:Glmn ^@ http://purl.uniprot.org/uniprot/Q8BZM1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Complete embryonic lethality. Embryos are present at the expected Mendelian rate at 10.5 dpc, but all are dead by 12.5 dpc. Mutant embryos display decreased growth, delayed neural tube closure, incomplete axial turning, pericardial effusion and a failure to form an organized, functional vascular network. Mutant embryos have reduced protein levels of FBXW7, RBX1, CUL1, CUL2, CUL3 and CUL4A, due to increased proteasome-mediated degradation, and increased levels of CCNE1 and MYC.|||Interacts with FKBP4 and FKBP1A. Interacts with RBX1 (via RING domain). Identified in complexes that contain RBX1 plus one of the cullins CUL1, CUL2, CUL3, and CUL4A. Identified in a SCF complex composed of CUL1, RBX1, SKP1, FBXW7 and GLMN. Component of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN. Interacts with unphosphorylated MET and is released upon MET phosphorylation.|||Phosphorylated on tyrosine residues.|||Regulatory component of cullin-RING-based SCF (SKP1-Cullin-F-box protein) E3 ubiquitin-protein ligase complexes. Inhibits E3 ubiquitin ligase activity by binding to the RING domain of RBX1 and inhibiting its interaction with the E2 ubiquitin-conjugating enzyme CDC34. Inhibits RBX1-mediated neddylation of CUL1 (By similarity). Required for normal stability and normal cellular levels of key components of SCF ubiquitin ligase complexes, including FBXW7, RBX1, CUL1, CUL2, CUL3, CUL4A, and thereby contributes to the regulation of CCNE1 and MYC levels (PubMed:22405651). Essential for normal development of the vasculature (PubMed:22405651). Contributes to the regulation of RPS6KB1 phosphorylation (By similarity).|||The C-terminal half of the protein is important for interaction with RBX1.|||Ubiquitous. Detected in embryonic vasculature and embryonic perichondrium, and in adult eye, brain, heart, testis, kidney, smooth muscle and skeletal muscle. http://togogenome.org/gene/10090:Lama1 ^@ http://purl.uniprot.org/uniprot/P19137 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Domains VI, IV and G are globular.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-1 is a subunit of laminin-1 (laminin-111 or EHS laminin) and laminin-3 (laminin-121 or S-laminin).|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||Tyrosine phosphorylated by PKDCC/VLK.|||basement membrane http://togogenome.org/gene/10090:Hspb1 ^@ http://purl.uniprot.org/uniprot/P14602|||http://purl.uniprot.org/uniprot/Q545F4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small heat shock protein (HSP20) family.|||Cytoplasm|||Homooligomer. Homodimer; becomes monomeric upon activation. Heterooligomer; with HSPB6. Associates with alpha- and beta-tubulin (By similarity). Interacts with TGFB1I1 (PubMed:11546764). Interacts with CRYAB (By similarity). Interacts with HSPB8 (PubMed:11342557). Interacts with HSPBAP1 (PubMed:10751411).|||Mice are viable and fertile with no apparent morphological abnormalities in tissues under physiological conditions.|||Nucleus|||Phosphorylated upon exposure to protein kinase C activators and heat shock (By similarity). Phosphorylation by MAPKAPK2 and MAPKAPK3 in response to stress dissociates HSPB1 from large small heat-shock protein (sHsps) oligomers and impairs its chaperone activity and ability to protect against oxidative stress effectively. Phosphorylation by MAPKAPK5 in response to PKA stimulation induces F-actin rearrangement (PubMed:1332886, PubMed:1860870, PubMed:21575178, PubMed:8093612).|||Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Plays a role in stress resistance and actin organization (PubMed:17661394). Through its molecular chaperone activity may regulate numerous biological processes including the phosphorylation and the axonal transport of neurofilament proteins (By similarity).|||spindle http://togogenome.org/gene/10090:Nus1 ^@ http://purl.uniprot.org/uniprot/Q99LJ8 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UPP synthase family.|||Contains the RXG motif, which is important for substrate binding and prenyltransferase activity. The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs.|||Endoplasmic reticulum membrane|||Forms an active dehydrodolichyl diphosphate synthase complex with DHDDS. Interacts with NPC2.|||Highly expressed in heart, liver, kidney and pancreas.|||Leads to early embryonic lethality in vivo and defective cis-prenyltransferase activity and cholesterol levels in isolated fibroblasts.|||NUS1 seems to exist in two topological orientations, a minor glycosylated species with its C-terminus oriented towards the lumen regulating NPC2 stability, and a major fraction oriented with its C-terminus directed towards the cytosol where it regulates cis-IPTase activity.|||With DHDDS, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length. Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol. Acts as a specific receptor for the N-terminus of Nogo-B, a neural and cardiovascular regulator. http://togogenome.org/gene/10090:Klf13 ^@ http://purl.uniprot.org/uniprot/Q9JJZ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Nucleus|||Transcription factor that activates expression from GC-rich minimal promoter regions, including genes in the cells of the erythroid lineage.|||Ubiquitous. http://togogenome.org/gene/10090:Far1 ^@ http://purl.uniprot.org/uniprot/Q922J9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fatty acyl-CoA reductase family.|||Catalyzes the reduction of saturated and unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols (PubMed:15220348, PubMed:15220349). It plays an essential role in the production of ether lipids/plasmalogens which synthesis requires fatty alcohols (By similarity). In parallel, it is also required for wax monoesters production since fatty alcohols also constitute a substrate for their synthesis (PubMed:15220349).|||Interacts with PEX19; PEX19 mediates the targeting of FAR1 to peroxisomes.|||Peroxisome membrane|||Widely expressed. Expressed in all tissues examined. Highest expression seen in preputial gland. Expressed in the brain where large quantities of ether lipids are synthesized. http://togogenome.org/gene/10090:Trim13 ^@ http://purl.uniprot.org/uniprot/Q9CYB0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated; requires the RING-type zinc finger. Auto-polyubiquitination leads to proteasomal degradation.|||Belongs to the TRIM/RBCC family.|||Endoplasmic reticulum (ER) membrane anchored E3 ligase involved in the retrotranslocation and turnover of membrane and secretory proteins from the ER through a set of processes named ER-associated degradation (ERAD). This process acts on misfolded proteins as well as in the regulated degradation of correctly folded proteins. Enhances ionizing radiation-induced p53/TP53 stability and apoptosis via ubiquitinating MDM2 and AKT1 and decreasing AKT1 kinase activity through MDM2 and AKT1 proteasomal degradation. Regulates ER stress-induced autophagy, and may act as a tumor suppressor. Also plays a role in innate immune response by stimulating NF-kappa-B activity in the TLR2 signaling pathway. Ubiquitinates TRAF6 via the 'Lys-29'-linked polyubiquitination chain resulting in NF-kappa-B activation. Participates as well in T-cell receptor-mediated NF-kappa-B activation. In the presence of TNF, modulates the IKK complex by regulating IKBKG/NEMO ubiquitination leading to the repression of NF-kappa-B.|||Endoplasmic reticulum membrane|||Interacts (via C-terminal domain) with VCP. Interacts with AKT1; the interaction ubiquitinates AKT1 and leads to its proteasomal degradation. Interacts with MDM2; the interaction ubiquitinates AKT1 and leads to its proteasomal degradation. Interacts with p62/SQSTM1. Interacts with TRAF6. Interacts with IKBKG/NEMO.|||The C-terminal transmembrane domain is indispensable for the localization to the ER.|||The RING-type zinc finger is required for auto-polyubiquitination.|||The coiled-coil domain is required for the induction of autophagy during endoplasmic reticulum (ER) stress. http://togogenome.org/gene/10090:Brd8 ^@ http://purl.uniprot.org/uniprot/Q8R3B7 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. BRD8 isoform 2 interacts with RXRA/NR2B1 and THRB/ERBA2. Component of a SWR1-like complex (By similarity).|||Intron retention.|||May act as a coactivator during transcriptional activation by hormone-activated nuclear receptors (NR). Stimulates transcriptional activation by AR/DHTR, ESR1/NR3A1, RXRA/NR2B1 and THRB/ERBA2. Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome.|||Nucleus http://togogenome.org/gene/10090:Ubox5 ^@ http://purl.uniprot.org/uniprot/Q925F4 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in embryos at 14.5 dpc.|||Expressed in testis and placenta.|||Interacts with UBE2L3. Interacts with VCP.|||May have a ubiquitin-protein ligase activity acting as an E3 ubiquitin-protein ligase or as a ubiquitin-ubiquitin ligase promoting elongation of ubiquitin chains on substrates.|||Nucleus|||The U-box domain mediates interaction with E2 ubiquitin ligases and is required for the ubiquitin-protein ligase activity. http://togogenome.org/gene/10090:Thsd7b ^@ http://purl.uniprot.org/uniprot/Q6P4U0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Polr1e ^@ http://purl.uniprot.org/uniprot/Q3V1B9|||http://purl.uniprot.org/uniprot/Q8K202 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated at Lys-436 by CREBBP/CBP, leading to decreased RNA polymerase I transcription. In normal conditions, deacetylated by SIRT7, promoting the association of RNA polymerase I with the rDNA promoter region and coding region. In response to stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased association of RNA polymerase I with the rDNA promoter region.|||Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (PubMed:9254723). Interacts with POLR1G (PubMed:15226435). Also binds UBTF/UBF (PubMed:8641287). Interacts with PWP1 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors (PubMed:8641287, PubMed:9254723). Appears to be involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBTF/UBF (PubMed:8641287).|||nucleolus http://togogenome.org/gene/10090:Sh3rf3 ^@ http://purl.uniprot.org/uniprot/Q8C120 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ Autoubiquitinated.|||Belongs to the SH3RF family.|||Has E3 ubiquitin-protein ligase activity.|||Interacts (via SH3 domain 3) with PAK2. Interacts with RAC1 (GTP-bound form).|||The RING finger domain is required for ubiquitin ligase activity and autoubiquitination. http://togogenome.org/gene/10090:Kcnd3 ^@ http://purl.uniprot.org/uniprot/B2RUE0|||http://purl.uniprot.org/uniprot/Q3UH54|||http://purl.uniprot.org/uniprot/Q9Z0V1 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.3/KCND3 sub-subfamily.|||Cell membrane|||Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DLG1, KCNE1, KCNE2, SCN1B and KCNAB1 (By similarity).|||May be due to intron retention.|||Membrane|||Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.|||Regulated through phosphorylation at Ser-569 by CaMK2D.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||dendrite|||sarcolemma http://togogenome.org/gene/10090:Or56b1 ^@ http://purl.uniprot.org/uniprot/Q7TRP7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Thoc3 ^@ http://purl.uniprot.org/uniprot/Q8VE80 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling.|||Nucleus|||Nucleus speckle|||Required for efficient export of polyadenylated RNA and spliced mRNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway (By similarity). http://togogenome.org/gene/10090:Vmn1r170 ^@ http://purl.uniprot.org/uniprot/K7N6W9 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Ptges3 ^@ http://purl.uniprot.org/uniprot/Q9R0Q7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the p23/wos2 family.|||Cytoplasm|||Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes. Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway.|||Expressed in testis, kidney, bladder and ovary.|||Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2. Binds to the progesterone receptor. Interacts with TERT; the interaction, together with HSP90AA1, is required for correct assembly and stabilization of the telomerase holoenzyme complex. Interacts (via PXLE motif) with EGLN1/PHD2, recruiting EGLN1/PHD2 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with HSP90AA1, FLCN, FNIP1 and FNIP2.|||Proteolytically cleaved by caspase-7 (CASP7) in response to apoptosis, leading to its inactivation. http://togogenome.org/gene/10090:Ptchd3 ^@ http://purl.uniprot.org/uniprot/Q0EEE2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the patched family.|||Endoplasmic reticulum membrane|||Expressed in germ cells of the testis (at protein level).|||Expression begins around the pachytene stage of spermatogenesis.|||May play a role in sperm development or sperm function (PubMed:17904097). However, does not appear to have an essential role in spermatogenesis or male fertility (PubMed:34493359).|||flagellum membrane http://togogenome.org/gene/10090:Usp51 ^@ http://purl.uniprot.org/uniprot/B1AY15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Chromosome|||Deubiquitinates histone H2A at 'Lys-13' and 'Lys-15' and regulates DNA damage response. USP51 is recruited to chromatin after DNA damage and regulates the dynamic assembly/disassembly of TP53BP1 and BRCA1 foci.|||Interacts with H2A. http://togogenome.org/gene/10090:Snrnp200 ^@ http://purl.uniprot.org/uniprot/Q6P4T2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. SKI2 subfamily.|||Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome. Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome.|||Component of a core complex containing at least PRPF8, SNRNP200, EFTUD2 and SNRNP40. Component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes, building blocks of the spliceosome. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Component of precatalytic, catalytic and postcatalytic spliceosomal complexes. Component of the minor spliceosome, which splices U12-type introns (By similarity). Interacts with C9orf78; the interaction is direct and mutually exclusive with its interaction with WBP4. Interacts with WBP4; the interaction is mutually exclusive with its interaction with C9orf78. Interacts with PRPF8. Interacts with TSSC4; the interaction is direct, excludes recruitment of C9ORF78 and WBP4 to SNRNP200 and negatively regulates its RNA helicase activity (By similarity).|||Contains two helicase domains. The N-terminal helicase domain has catalytic activity by itself, contrary to C-terminal helicase domain that may have a regulatory role and enhance the activity of the first helicase domain.|||Nucleus http://togogenome.org/gene/10090:Vmn2r113 ^@ http://purl.uniprot.org/uniprot/E9PZA6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or10q1b ^@ http://purl.uniprot.org/uniprot/Q8VEZ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cdh9 ^@ http://purl.uniprot.org/uniprot/F8WHU6 ^@ Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cct3 ^@ http://purl.uniprot.org/uniprot/P80318|||http://purl.uniprot.org/uniprot/Q3U4U6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG (By similarity). Interacts with DNAAF4 (PubMed:23872636). Interacts with DLEC1 (By similarity).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||The N-terminus is blocked. http://togogenome.org/gene/10090:Ptchd1 ^@ http://purl.uniprot.org/uniprot/Q14B62 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the patched family.|||Broadly expressed in the brain (PubMed:20844286). Selectively expressed in the thalamic reticular nucleus (TRN) in early development and continues to be enriched in this structure throughout adult life (PubMed:27007844).|||Cell membrane|||Mice show decreased spindles and sleep fragmentation, learning defects, hyper-aggressive behavior and motor defects. Selective deletion in the thalamic reticular nucleus (TRN) leads to attention deficits and hyperactivity. Defects are probably due to dcreased TRN activity through mechanisms involving small conductance calcium-dependent potassium currents (SK).|||Required for the development and function of the thalamic reticular nucleus (TRN), a part of the thalamus that is critical for thalamocortical transmission, generation of sleep rhythms, sensorimotor processing and attention.|||Widely expressed in the developing brain from 9.5 day post coitum (dpc) to postnatal day 1 (P1) (PubMed:20844286). Specifically expressed in the thalamic reticular nucleus (TRN) at birth. Expressed in the striatum, cortex and cerebellum by P15 onwards (PubMed:27007844). http://togogenome.org/gene/10090:Sqle ^@ http://purl.uniprot.org/uniprot/P52019|||http://purl.uniprot.org/uniprot/Q3TQK8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the squalene monooxygenase family.|||Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.|||Detected in liver.|||Endoplasmic reticulum membrane|||Interacts (via N-terminal domain) with MARCHF6. Interacts with SMIM22; this interaction modulates lipid droplet formation.|||Microsome membrane|||The C-terminal hydrophobic region contains two helices that mediate interaction with membranes. Contrary to predictions, this region does not contain transmembrane helices.|||The N-terminal region mediates interaction with MARCHF6, leading to SQLE ubiquitination and proteasomal degradation when cholosterol levels are high. The first part of the N-terminal region contains a hydrophobic region that inserts into the membrane; contrary to predictions, there are no transmembrane helices. The second part contains a region that can form an amphipathic region that associates with membranes. This region is ejected from the membrane by high cholesterol levels and becomes disordered in an aqueous environment. This is critical for cholesterol-dependent proteasomal degradation. Additional parts of the N-terminal region are predicted to be disordered and contribute to flagging the protein for proteasomal degradation already under basal conditions.|||Ubiquitinated by MARCHF6 in response to high cholesterol levels in intracellular membranes, leading to proteasomal degradation. http://togogenome.org/gene/10090:Cend1 ^@ http://purl.uniprot.org/uniprot/Q9JKC6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CEND1 family.|||Expressed in the brain, including hypothalamus, brainstem, and hippocampus. Expression is high in 1-month-old mouse brain and then declines in mature mouse brains at the age of 3 and 7 months.|||Homodimer (By similarity). Interacts with AHI1 (PubMed:23658157).|||Involved in neuronal differentiation.|||Membrane http://togogenome.org/gene/10090:Or12e1 ^@ http://purl.uniprot.org/uniprot/A2ATA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4z4 ^@ http://purl.uniprot.org/uniprot/Q8VFU9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd81 ^@ http://purl.uniprot.org/uniprot/P35762 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Mutant mice are refractory to Plasmodium yoelii sporozoite infection.|||(Microbial infection) Specifically required for Plasmodium yoelii infectivity of hepatocytes, controlling sporozoite entry in hepatocytes via the parasitophorous vacuole and subsequent parasite differentiation to exoerythrocytic forms.|||Basolateral cell membrane|||Belongs to the tetraspanin (TM4SF) family.|||Binds cholesterol in a cavity lined by the transmembrane spans.|||Cell membrane|||Expressed in oocytes (at protein level) (PubMed:16380109, PubMed:17290409, PubMed:23213457). Highly expressed in granulosa cells (PubMed:16380109). Expressed in skeletal muscle mainly in endothelial cells of endomysial capillaries, in satellite cells and myoblasts (at protein level) (PubMed:23575678). Expressed in hepatocytes (at protein level) (PubMed:12483205).|||Homodimer (By similarity). Part of a complex composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of mature B cells. Interacts (via the second extracellular domain) with CD19; this interaction is initiated early during biosynthesis in the ER and enables trafficking of only properly folded CD19 (By similarity). Part of a complex that includes MHC class II/HLA-DR molecules and IFITM1. Interacts with IFITM1 (By similarity). Interacts with IFITM2 and IFITM3 (PubMed:16395393). Part of integrin-tetraspanin complex composed of CD9, CD81, beta-1 and beta-2 integrins in the membrane of monocyte/macrophages (By similarity). Interacts (via the second extracellular domain) with integrin ITGAV:ITGB3 (By similarity). Interacts with CD247/CD3 zeta, ICAM1 and CD9 at the immune synapse on T cell membrane (By similarity). Part of a GPCR-tetraspanin complex consisting at least of ADGRG1, CD81, possibly CD9, and GNA11 in which CD81 enhances the association of ADGRG1 with GNA11 (By similarity). Part of a complex composed of CD9, CD81, PTGFRN and IGSF8 (PubMed:23575678). Interacts directly with IGSF8 (PubMed:11673522). Interacts with CD53 and SCIMP (By similarity). Interacts with SAMHD1 (via its C-terminus) (By similarity). Interacts with glypican GPC3 and with the transcriptional repressor HHEX; binding to GPC3 decreases the availability of free CD81 for binding to HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (PubMed:23665349). Interacts with CLDN1 (By similarity). Interacts with CLDN6 and CLDN9 (By similarity).|||Knockout mice exhibit reduced female fertitily and impaired egg-sperm fusion (PubMed:16380109, PubMed:17290409). In response to notexin-induced acute myoinjury, mutant mice display abnormal muscle regeneration characterized by typical giant distrophic myofibres (PubMed:23575678). Mutant mice show reduced allergen-induced lung inflammation, eosinophilia and mucin production (PubMed:11046035). These mice spontaneously develop multinucleated giant cells (MGCs) and show enhanced osteoclastogenesis when compared to wild-type littermates (PubMed:12796480). CD81 and CD9 double knockout mice develop pulmonary emphysema, reminiscent of chronic obstructive pulmonary disease in human (PubMed:18662991).|||Likely constitutively palmitoylated at low levels. Protein palmitoylation is up-regulated upon coligation of BCR and CD9-C2R-CD81 complexes in lipid rafts.|||Not glycosylated.|||Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking and compartmentalization of CD19 receptor on the cell surface of activated B cells (PubMed:23499492). Upon initial encounter with a microbial pathogen, enables the assembly of CD19-CR2 and B cell receptor complexes at signaling TERMs, lowering the threshold dose of antigen required to trigger B cell clonal expansion and humoral immune response (By similarity). In T cells, associates with CD4 or CD8 coreceptors and defines the maturation state of antigen-induced synapses with B cells (By similarity). Facilitates localization of CD3 in these immune synapses, required for costimulation and sustained activation of T cells, preferentially triggering T helper type 2 immune response (PubMed:11046035). Can act both as positive and negative regulator of homotypic or heterotypic cell-cell fusion processes. In myoblasts, associates with another tetraspanin CD9 in complex with PTGFRN and inhibits myotube fusion during muscle regeneration (PubMed:23575678). In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles. Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption. Positively regulates sperm-egg fusion and may be involved in the acrosome reaction (PubMed:16380109, PubMed:17290409). Regulates protein trafficking in intracellular compartments. In T cells, associates with dNTPase SAMHD1 and defines its subcellular location, enabling its degradation by the proteasome and thereby controlling intracellular dNTP levels (By similarity). Also regulates integrin-dependent migration of macrophages, particularly relevant for inflammatory response in the lung (PubMed:18662991).|||Up-regulated in response to notexin-induced acute myoinjury. http://togogenome.org/gene/10090:Akr1b8 ^@ http://purl.uniprot.org/uniprot/P45377 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldo/keto reductase family.|||By FGF-1.|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Sntg2 ^@ http://purl.uniprot.org/uniprot/Q8BZG8|||http://purl.uniprot.org/uniprot/Q925E0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that binds to and probably organizes the subcellular localization of a variety of proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex (By similarity).|||Belongs to the syntrophin family.|||Interacts with the dystrophin protein DMD and related proteins DTNA and DTNB.|||The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Pde6a ^@ http://purl.uniprot.org/uniprot/Q8K0A8 ^@ Cofactor|||Similarity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. http://togogenome.org/gene/10090:Sema6a ^@ http://purl.uniprot.org/uniprot/D3YWM8|||http://purl.uniprot.org/uniprot/O35464|||http://purl.uniprot.org/uniprot/Q8BUT0|||http://purl.uniprot.org/uniprot/Q8BXZ7 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Active as a homodimer or oligomer. The SEMA6A homodimer interacts with a PLXNA2 homodimer, giving rise to a heterotetramer. Interacts with EVL.|||Belongs to the semaphorin family.|||Cell membrane|||Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||No visible phenotype. Mice are viable and fertile, and do not show any major behavioral defects. In developing cerebellum, migration of granule cells is impaired. Granule cells can form normal cell processes, but the movement of the nucleus seems to be impaired.|||Particularly high levels in spinal cord, cerebellum, metencephalon, superior and inferior colliculus, diencephalon, olfactory bulb and eye.|||Temporally and spatially regulated during development. http://togogenome.org/gene/10090:Ttc19 ^@ http://purl.uniprot.org/uniprot/Q8CC21 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TTC19 family.|||Binds to the mature mitochondrial complex III dimer, after the incorporation of the Rieske protein UQCRFS1 (PubMed:28673544, PubMed:21278747). Interacts with UQCRC1 and UQCRFS1 (PubMed:21278747). Interacts with ZFYVE26 and CHMP4B (By similarity).|||Mitochondrion inner membrane|||Mutant mice show progressive neurological and energy metabolic decline, decrease complex III activity, increased production of reactive oxygen species, extensive astrogliosis and accumulation of ubiquitinated proteins in neurons of the thalamus. Compatible with a Mendelian autosomal recessive trait. No evidence of embryonic lethality nor evidence of obvious neuronal loss.|||Proteolytically cleaved by PARL.|||Required for the preservation of the structural and functional integrity of mitochondrial respiratory complex III by allowing the physiological turnover of the Rieske protein UQCRFS1 (PubMed:21278747, PubMed:28673544). Involved in the clearance of UQCRFS1 N-terminal fragments, which are produced upon incorporation into the complex III and whose presence is detrimental for its catalytic activity (PubMed:28673544). http://togogenome.org/gene/10090:Tmem231 ^@ http://purl.uniprot.org/uniprot/Q3U284 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM231 family.|||Embryos die around 15.5 dpc with severe vascular defects. 10.5 dpc mutant embryos have defects in patterning of the ventral spinal cord that are characteristic of defects in Shh signaling. 14.5 dpc embryos exhibit microphthalmia and polydactyly, consistent with disruptions in Shh signaling.|||Part of the tectonic-like complex (also named B9 complex) (PubMed:22179047). Interacts with TMEM107 (By similarity).|||Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling.|||cilium membrane http://togogenome.org/gene/10090:Zfp39 ^@ http://purl.uniprot.org/uniprot/Q02525 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ A putative DNA-binding regulatory protein associated with meiosis in spermatogenesis.|||First detected between 2 and 3 weeks after birth, in parallel with the onset and progression of meiosis.|||Nucleus|||Predominantly in the spermatocytes and spermatids of testes. http://togogenome.org/gene/10090:Or10ag53 ^@ http://purl.uniprot.org/uniprot/Q7TR53 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adar ^@ http://purl.uniprot.org/uniprot/Q99MU3 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By inflammation. Under normal conditions, long forms starting at Met-1 are dominant. Inflammation causes selective induction of short forms starting at Met-519.|||Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Does not affect polyomavirus replication but provides protection against virus-induced cytopathic effects. Essential for embryonic development and cell survival and plays a critical role in the maintenance of hematopoietic stem cells.|||Cytoplasm|||Highest levels in brain and spleen. Lowest levels in liver.|||Homodimer. Homodimerization is essential for its catalytic activity (PubMed:12618436). Isoform 5 can form heterodimers with ADARB1/ADAR2. Isoform 1 and isoform 5 (via DRBM 3 domain) interact with TNPO1. Isoform 5 (via DRBM domains) interacts with XPO5. Isoform 1 and isoform 5 can interact with UPF1 (By similarity). Isoform 1 interacts with ILF2/NF45 and ILF3/NF90 (PubMed:16055709). Binding to ILF3/NF90 up-regulates ILF3-mediated gene expression. Isoform 1 and isoform 5 interact with EIF2AK2/PKR (PubMed:17079286).|||Mice do not survive past 11.0-12.5 dpc, and embryos display widespread apoptosis, a rapidly disintegrating liver structure and severe defects in hematopoiesis.|||Sumoylation reduces RNA-editing activity.|||The first Z-binding domain binds Z-DNA.|||The third dsRNA-binding domain (DRBM 3) contains an additional N-terminal alpha-helix that is part of a bi-partite nuclear localization signal, together with the sequence immediately C-terminal to DRBM 3. The presence of DRBM 3 is important to bring together the N-terminal and the C-terminal part of the bi-partite nuclear localization signal for import mediated by TNPO1. RNA binding interferes with nuclear import.|||nucleolus http://togogenome.org/gene/10090:Cdh10 ^@ http://purl.uniprot.org/uniprot/P70408 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.|||Cell membrane|||Expressed at all stages of testicular development with highest levels found in fetal gonad.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Atp5k ^@ http://purl.uniprot.org/uniprot/Q06185 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATPase e subunit family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mammary gland, liver, kidney, heart, spleen, brain and lung.|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Strn4 ^@ http://purl.uniprot.org/uniprot/P58404 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat striatin family.|||Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein.|||Cytoplasm|||Interacts with CTTNBP2; this interaction may regulate dendritic spine distribution of STRN4. Activation of glutamate receptors weakens the interaction with CTTNBP2 (By similarity). Interacts with CTTNBP2NL (By similarity).|||Mainly expressed in brain but is also expressed at low levels in the kidney.|||Membrane|||The name 'Zinedin' probably originates from the name of the famous soccer player from Marseille (Zinedine Zidane).|||dendritic spine http://togogenome.org/gene/10090:Skint6 ^@ http://purl.uniprot.org/uniprot/A7XUZ6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Trim29 ^@ http://purl.uniprot.org/uniprot/Q8R2Q0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Absence of TRIM29 enhances macrophage production of type I interferons and protects mice from infection with influenza virus.|||Cytoplasm|||Interacts with VIM and HINT1. Interacts with IKBKG/NEMO. Interacts with STING1.|||Lysosome|||Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. Mechanistically, TRIM29 interacts with IKBKG/NEMO in the lysosome where it induces its 'Lys-48' ubiquitination and subsequent degradation. In turn, the expression of type I interferons and the production of pro-inflammatory cytokines are inhibited. Additionally, induces the 'Lys-48' ubiquitination of STING1 in a similar way, leading to its degradation. http://togogenome.org/gene/10090:Marcks ^@ http://purl.uniprot.org/uniprot/P26645 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MARCKS family.|||Brain, spleen, less in kidney and heart, and very low levels in liver.|||By lipopolysaccharides (LPS).|||MARCKS is the most prominent cellular substrate for protein kinase C. This protein binds calmodulin, actin, and synapsin. MARCKS is a filamentous (F) actin cross-linking protein.|||Membrane|||Phosphorylation by PKC displaces MARCKS from the membrane. It also inhibits the F-actin cross-linking activity.|||cytoskeleton http://togogenome.org/gene/10090:Hoxd13 ^@ http://purl.uniprot.org/uniprot/P70217 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||It is uncertain whether Met-1 or Met-9 is the initiator.|||Nucleus|||Sequence-specific transcription factor that binds gene promoters and activates their transcription (PubMed:23995701). Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis (By similarity). http://togogenome.org/gene/10090:Slitrk1 ^@ http://purl.uniprot.org/uniprot/Q810C1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLITRK family.|||Can form homodimers; homodimerization requires repeat LRR 2 (By similarity). Interacts with YWHAB, YWHAE, YWHAG, YWHAH, SFN, YWHAQ and YWHAZ (By similarity).|||In the adult, significant expression is detected only in the brain. Broadly expressed in embryonic brain with highest expression in subventricular zone, subplate, cortical plate, pyramidal cell layer of hippocampus, thalamus and hypothalamus where levels are highest in ventromedial hypothalamus and medial part of periaqueductal gray matter. Also expressed in mantle layer of spinal cord and in lateral and medial motor columns.|||In the embryo, expressed from day 10-12 and continues through later gestational development and into adulthood.|||It is involved in synaptogenesis and promotes excitatory synapse differentiation (By similarity). Enhances neuronal dendrite outgrowth (PubMed:14550773).|||Membrane|||Secreted|||Synapse|||Undergoes proteolytic cleavage that results in shedding of the ectodomain and cleavage of the C-terminal cytoplasmic tail. Glycosylated. Phosphorylation at Ser-695 is necessary for proper function in promoting neurite outgrowth. http://togogenome.org/gene/10090:Arpc5 ^@ http://purl.uniprot.org/uniprot/Q9CPW4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ARPC5 family.|||Cell projection|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC.|||Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Nucleus|||Polyubiquitinated by RNF128 with 'Lys-63'-linked chains, leading to proteasomal degradation.|||cytoskeleton http://togogenome.org/gene/10090:Tle6 ^@ http://purl.uniprot.org/uniprot/D3Z5E1|||http://purl.uniprot.org/uniprot/Q9WVB3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:18804437, PubMed:25208553). Required for the formation of F-actin cytoplasmic lattices in oocytes which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning (PubMed:31575650). Regulates spermatogonia proliferation and cell cycle progression, potentially via regulation of cell cycle regulatory genes such as; CEBPB, CEBPA, CSF3, PCNA, and CDK4 (PubMed:32823735). Suppresses FOXG1/BF-1-mediated transcriptional repression by inhibiting interaction of the transcriptional corepressor TLE1 with FOXG1 which promotes cortical neuron differentiation (PubMed:16314515). Acts as a transcriptional corepressor of NFATC1-mediated gene expression by contributing to PAX6-mediated repression (PubMed:23990468).|||Belongs to the WD repeat Groucho/TLE family.|||Contrary to other WD repeat Groucho/TLE family members, does not contain any identifiable Q, GP, CcN or SP domains. Only the C-terminal WD-repeat domain is conserved.|||Cytoplasm|||Expressed in spermatogonia (at protein level) (PubMed:32823735). Expressed predominantly in ovaries, where it is restricted to growing oocytes, with greatest levels in fully grown oocytes (PubMed:18804437, PubMed:25208553). Expressed predominantly in testis, heart, lung, liver and muscle, and at very low levels in the brain, spleen and kidney (PubMed:11486032). Expressed in bone marrow-derived macrophages and osteoclasts (PubMed:23990468).|||Females show normal ovarian histology, ovulation and egg morphology, however fail to produce offspring following successful mating (PubMed:25208553). Progression from one- to two-cell embryos is delayed by 4-6 hours and embryos failed to develop into morulae and blastocysts (PubMed:25208553). Embryos form unequal sized blastomeres due to smaller, dysmorphic, and displaced mitotic spindles resulting to asymmetric division (PubMed:25208553). Loss of FMN2-expressing endoplasmic reticulum localization to the mitotic spindle periphery, and incorrect localization of mitochondria to the subcortical region prior to nuclear envelope breakdown in zygotes and oocytes (PubMed:28992324). Extension of the alpha-tubulin pool into the subcortical region following microtubule-organizing center congression in oocytes (PubMed:28992324). Decrease in expression of the SCMC components ZBED3, NLRP5/MATER, KHDC3/FILIA and OOEP/FLOPED in oocytes (PubMed:25208553, PubMed:28992324). Loss of F-actin cytoplasmic lattices in oocytes, zygotes and embryos (PubMed:25208553, PubMed:31575650). Decrease in thickness of subcortical F-actin in zygotes and thickening of F-actin bundles in the cytoplasm is evident (PubMed:25208553). Decrease in CFL1/Cofilin-1 expression in the subcortex, diffused distribution in the cytoplasm of zygotes and decrease in phosphorylated CFL1/Cofilin-1 expression in oocytes and zygotes (PubMed:25208553).|||Homodimers (PubMed:16314515). Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and TLE6 (PubMed:18804437, PubMed:28992324). Within the complex, interacts with NLRP5, KHDC3 and OOEP (PubMed:28992324, PubMed:31575650). The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments (By similarity). As part of the SCMC interacts with the SCMC-associated protein ZBED3 (PubMed:31575650). As part of the SCMC interacts with the SCMC-associated protein NLRP4F (PubMed:31575650). As part of the SCMC interacts with the SCMC-associated protein CFL1/Cofilin-1 (PubMed:25208553). Interacts with FOXG1/BF-1; the interaction inhibits TLE1 interaction with FOXG1/BF-1 (PubMed:16314515). Interacts with NFATC1 (PubMed:23990468). Interacts with PAX6 (PubMed:23990468).|||Induced by E2A-HLF, a chimeric transcription factor containing the transactivation domain of E2A linked to the DNA-binding and dimerization domain of HLF (PubMed:11486032). Induced during TNFSF11/RANKL-induced osteoclast differentiation (PubMed:23990468).|||Nucleus|||Transcripts first detected at 15.5 dpc and peak 1 week after birth. Transcripts accumulate during oogenesis (PubMed:18804437). During meiotic maturation, the vast majority of the transcripts are degraded and virtually none is detected by 2-cell stage embryogenesis (PubMed:18804437). The protein however persists during preimplantation up to the blastocyst stage (PubMed:18804437). At 2-cell stage, excluded from cell-cell contact regions. Continuous exclusion from these regions during preimplantation development leads to the absence of the protein from the inner cells of the morula and the inner cell mass of the blastocyst (PubMed:18804437). Expressed in the forebrain, midbrain, ventricular zone and superficial cortical plate at 14.5 dpc (PubMed:16314515). Expressed in cortical progenitors in the forebrain dorsal telencephalon and the midbrain at 15.5 dpc (PubMed:16314515). Expressed in ovaries at postnatal day 2 (P2), expression peaks at P10, expression is then decreased at P17 and further decreased at P21 (PubMed:31575650). http://togogenome.org/gene/10090:Hoxb1 ^@ http://purl.uniprot.org/uniprot/P17919 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family. Labial subfamily.|||Expressed along the entire length of the primitive streak. In early neurogenesis it is expressed in lateral and paraxial mesoderm, endoderm and superficial ectoderm or in the neural tube. From late neurogenesis to mid-embryogenesis, it presents similar spatial domains in the lateral mesoderm, endoderm and superficial ectoderm but is not detectable in the posterior hindbrain and has increased dramatically in rhombomere 4.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. http://togogenome.org/gene/10090:Or2t44 ^@ http://purl.uniprot.org/uniprot/Q7TRZ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ttyh2 ^@ http://purl.uniprot.org/uniprot/Q3TH73 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tweety family.|||Cell membrane|||Probable large-conductance Ca(2+)-activated chloride channel. May play a role in Ca(2+) signal transduction. May be involved in cell proliferation and cell aggregation (By similarity). http://togogenome.org/gene/10090:Gata1 ^@ http://purl.uniprot.org/uniprot/P17679 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated on Lys-233, Lys-245 Lys-246 by EP300 (By similarity). Acetylated on Lys-246, Lys-252 and Lys-312 by CREBBP in vitro. Acetylation does not affect DNA-binding in vitro but is essential to induce erythroid differentiation and for binding chromatin in vivo.|||Detected at 11.5-day fetal livers (at protein level). Isoform 2 detected earlier at 8.5-day embryo.|||Erythrocytes. Expressed (at protein level) in liver.|||Highly phosphorylated on serine residues. Phosphorylation on Ser-310 is enhanced on erythroid differentiation. Phosphorylation on Ser-142 promotes sumoylation on Lys-137 (By similarity).|||May form homodimers or heterodimers with other isoforms. Interacts (via the N-terminal zinc finger) with ZFPM1 (By similarity). Interacts with GFI1B. Interacts with PIAS4; the interaction enhances sumoylation and represses the transactivational activity in a sumoylation-independent manner. Interacts with LMCD1. Interacts with CREBBP; the interaction stimulates acetylation and transcriptional activity in vivo. Interacts with BRD3. Interacts with MED1, CCAR1 and CALCOCO1. Interacts with EP300 (By similarity). Interacts with CEBPE (By similarity).|||Nucleus|||Produced by alternative initiation at Met-84 of isoform 1. Less effective than isoform 1 in its ability to transactivate target genes.|||Sumoylation on Lys-137 is enhanced by phosphorylation on Ser-142 and by interaction with PIAS4. Sumoylation with SUMO1 has no effect on transcriptional activity.|||The two fingers are functionally distinct and cooperate to achieve specific, stable DNA binding. The first finger is necessary only for full specificity and stability of binding, whereas the second one is required for binding.|||Transcriptional activator or repressor which probably serves as a general switch factor for erythroid development. It binds to DNA sites with the consensus sequence 5'-[AT]GATA[AG]-3' within regulatory regions of globin genes and of other genes expressed in erythroid cells. Activates the transcription of genes involved in erythroid differentiation of K562 erythroleukemia cells, including HBB, HBG1/2, ALAS2 and HMBS (By similarity). http://togogenome.org/gene/10090:Slc25a43 ^@ http://purl.uniprot.org/uniprot/A2A3V2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Becn2 ^@ http://purl.uniprot.org/uniprot/P0DM65 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the beclin family.|||Cytoplasm|||Decreased embryonic viability: embryonic and postnatal survival rates of homozygous mutant mice are markedly lower. Heterozygous knockout mice show defects in autophagy, increased levels of Cnr1 receptor, elevated food intake, and obesity and insulin resistance.|||Expressed in brain, skeletal muscle, placenta, thymus and uterus. Expressed at a lower level in liver, testis, stomach, and 17-day-old embryos.|||Homodimer (via coiled-coil domain) (By similarity). Interacts (via coiled-coil domain) with ATG14 (via coiled-coil domain); this interaction is tighter than BECN2 self-association (PubMed:23954414). Interacts with AMBRA1, UVRAG and PIK3C3/VPS34; these interactions are not disrupted by starvation (PubMed:23954414). Does not interact with RUBCN. Interacts (via N-terminus) with GPRASP1/GASP1; the interaction is direct (PubMed:23954414).|||Involved in 2 distinct lysosomal degradation pathways: acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover. Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1. http://togogenome.org/gene/10090:Lmbr1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFX9|||http://purl.uniprot.org/uniprot/Q9JIT0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LIMR family.|||Membrane|||Putative membrane receptor. http://togogenome.org/gene/10090:Usp49 ^@ http://purl.uniprot.org/uniprot/Q6P9L4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Component of a complex with RUVBL1 and PSMC5.|||Nucleus|||Specifically deubiquitinates histone H2B at 'Lys-120' (H2BK120Ub). H2BK120Ub is a specific tag for epigenetic transcriptional activation and acts as a regulator of mRNA splicing. Deubiquitination is required for efficient cotranscriptional splicing of a large set of exons (By similarity). http://togogenome.org/gene/10090:H2ac1 ^@ http://purl.uniprot.org/uniprot/Q8CGP4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Coa4 ^@ http://purl.uniprot.org/uniprot/Q8BT51 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the COA4 family.|||Mitochondrion|||Putative COX assembly factor. http://togogenome.org/gene/10090:Kdm5d ^@ http://purl.uniprot.org/uniprot/Q62240 ^@ Cofactor|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JARID1 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May play a role in spermatogenesis. Involved in transcriptional repression of diverse metastasis-associated genes; in this function seems to cooperate with ZMYND8. Suppresses prostate cancer cell invasion. Regulates androgen receptor (AR) transcriptional activity by demethylating H3K4me3 active transcription marks (By similarity).|||Interacts withPCGF6, MSH5, ZMYND8, AR.|||KDM5D encodes an H-Y epitope that is defined by the octamer peptide TENSGKDI; since no similar peptide was found in KDM5C, it is presumably the genetic basis for the antigenic difference between males and females that contributes toward a tissue transplant rejection response.|||May be due to an intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||The JmjC domain is required for enzymatic activity. http://togogenome.org/gene/10090:Dhodh ^@ http://purl.uniprot.org/uniprot/O35435 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily.|||Binds 1 FMN per subunit.|||Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Required for UMP biosynthesis via de novo pathway.|||Mitochondrion inner membrane|||Monomer.|||The uncleaved transit peptide is required for mitochondrial targeting and proper membrane integration. http://togogenome.org/gene/10090:Plxna2 ^@ http://purl.uniprot.org/uniprot/P70207 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the plexin family.|||Cell membrane|||Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.|||Homodimer. Interacts with RND1 (By similarity). Interacts directly with NRP1 and NRP2. The PLXNA2 homodimer interacts with a SEMA6A homodimer, giving rise to a heterotetramer. http://togogenome.org/gene/10090:Mrgprb2 ^@ http://purl.uniprot.org/uniprot/Q3KNA1|||http://purl.uniprot.org/uniprot/W8W3G3 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||In spite of its official gene name, this protein may be the functional ortholog of human MRGPRX2, in terms of expression pattern and pharmacology.|||Mast cell-specific receptor for basic secretagogues, i.e. cationic amphiphilic drugs, as well as endo- or exogenous peptides, consisting of a basic head group and a hydrophobic core. Recognizes and binds small molecules containing a cyclized tetrahydroisoquinoline (THIQ), such as non-steroidal neuromuscular blocking drugs (NMBDs), including tubocurarine and atracurium. In response to these compounds, mediates pseudo-allergic reactions characterized by histamine release, inflammation and airway contraction (PubMed:25517090).|||Mast cell-specific.|||Membrane|||No visible phenotype in normal conditions. Absence of pseudo-allergic reactions in response to small-molecule therapeutic drugs: secretagogue-induced histamine release, inflammation and airway contraction are abolished. http://togogenome.org/gene/10090:Zfp473 ^@ http://purl.uniprot.org/uniprot/Q8BI67 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with the SLBP/pre-mRNA complex but not with SLBP alone. Interacts with LSM11 in a U7 snRNP-dependent manner (By similarity).|||Involved in histone 3'-end pre-mRNA processing by associating with U7 snRNP and interacting with SLBP/pre-mRNA complex. Increases histone 3'-end pre-mRNA processing but has no effect on U7 snRNP levels, when overexpressed. Required for cell cycle progression from G1 to S phases (By similarity).|||Nucleus|||The C2H2-type zinc fingers are involved in discrete Cajal bodies localization, interaction with LSM11 and the SLBP/RNA complex and histone pre-mRNA processing. http://togogenome.org/gene/10090:F10 ^@ http://purl.uniprot.org/uniprot/O88947|||http://purl.uniprot.org/uniprot/Q3TBR2|||http://purl.uniprot.org/uniprot/Q3U3V1|||http://purl.uniprot.org/uniprot/Q80Y26 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.|||Inhibited by SERPINA5.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N- and O-glycosylated.|||Plasma; synthesized in the liver.|||Proteolytically cleaved and activated by cathepsin CTSG (By similarity). The activation peptide is cleaved by factor IXa (in the intrinsic pathway), or by factor VIIa (in the extrinsic pathway) (By similarity).|||Secreted|||The two chains are formed from a single-chain precursor by the excision of two Arg residues and are held together by 1 or more disulfide bonds. Forms a heterodimer with SERPINA5 (By similarity).|||The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium. http://togogenome.org/gene/10090:Sv2a ^@ http://purl.uniprot.org/uniprot/Q9JIS5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with C.botulinum neurotoxin type A (BoNT/A, botA).|||(Microbial infection) Possible receptor for C.botulinum neurotoxin type D (BoNT/D, botD); BoNT/D does not bind to extracellular loop 4 as do BoNT/A and BoNT/E (PubMed:21483489).|||(Microbial infection) Receptor for C.botulinum neurotoxin type A (BoNT/A, botA); the toxin probably binds via extracellular loop 4 (PubMed:16543415).|||(Microbial infection) Receptor for C.botulinum neurotoxin type E (BoNT/E); the toxin probably binds via extracellular loop 4 (PubMed:18815274). It probably requires glycosylation of Asn-573 (PubMed:18815274).|||Belongs to the major facilitator superfamily.|||Expressed during synaptogenesis in the retina (at protein level).|||Expressed in conventional synapses and cone ribbon synapses in the retina (at protein level) (PubMed:12687700). Expressed in diaphragm motor nerve terminals (at protein level) (PubMed:16543415). Expressed in hippocampus neurons (at protein level) (PubMed:18815274).|||Interacts with SYT1/synaptotagmin-1 in a calcium-dependent manner. Binds the adapter protein complex AP-2 (By similarity).|||Mice fail to grow, experience severe epileptic seizures and die immediately or shortly after birth probably due to multiple neural and endocrine deficits (PubMed:10624962). Mice lacking both Sv2a and Sv2b display a similar phenotype (PubMed:10624962). Diaphragm motor nerve terminals from mice with only a single copy of this gene and no Sv2b have decreased binding of C.botulinum neurotoxin type A (BoNT/A, botA) and are less sensitive to the toxin (PubMed:16543415). Hippocampal neurons from young mice lacking both Sv2a and Sv2b do not bind BoNT/A, nor do they take it up (PubMed:16543415, PubMed:18815274). Hippocampal neurons from young mice lacking both Sv2a and Sv2b do not bind C.botulinum neurotoxin type E (BoNT/E), nor do they take it up (PubMed:18815274). Hippocampal neurons from young mice lacking both Sv2a and Sv2b do not bind C.botulinum neurotoxin type BoNT/D (BoNT/D, botD), nor do they take it up (PubMed:21483489). Hippocampal neurons from young mice lacking both Sv2a and Sv2b take up C.botulinum neurotoxin type C (BoNT/C) and C.botulinum neurotoxin type F (BonT/F, botF) normally (PubMed:21483489).|||N-glycosylated.|||Phosphorylation by CK1 of the N-terminal cytoplasmic domain regulates interaction with SYT1.|||Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles.|||Presynapse|||synaptic vesicle membrane http://togogenome.org/gene/10090:Lman1 ^@ http://purl.uniprot.org/uniprot/Q9D0F3 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Exists both as a covalent disulfide-linked homohexamer, and a complex of three disulfide-linked dimers non-covalently kept together. Interacts with MCFD2. May interact with TMEM115. Interacts with RAB3GAP1 and RAB3GAP2. Interacts with UBXN6. Interacts with SERPINA1/alpha1-antitrypsin (By similarity).|||Golgi apparatus membrane|||Mannose-specific lectin. May recognize sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors and may be involved in the sorting or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins (By similarity).|||The FF ER export motif at the C-terminus is not sufficient to support endoplasmic reticulum exit, and needs assistance of Gln-508 for proper recognition of COPII coat components. http://togogenome.org/gene/10090:Rsph3a ^@ http://purl.uniprot.org/uniprot/Q3UFY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the flagellar radial spoke RSP3 family.|||May be a component of axonemal radial spokes (By similarity). Interacts with IQUB (By similarity). Interacts with phosphorylated MAPK1. Interacts with MEK1. Interacts with PKA regulatory subunits PRKAR1A and PRKAR1B (By similarity). Interacts with RSPH1. Interacts with RSPH4A. Interacts with RSPH6A. Interacts with RSPH9 (By similarity).|||May function as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (By similarity). Functions as a protein kinase A-anchoring protein that scaffolds the cAMP-dependent protein kinase holoenzyme. May serve as a point of convergence for MAPK and PKA signaling in cilia (By similarity).|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Coro2a ^@ http://purl.uniprot.org/uniprot/B1AVH4|||http://purl.uniprot.org/uniprot/B1AVH5|||http://purl.uniprot.org/uniprot/Q8C0P5 ^@ Similarity|||Subunit ^@ Belongs to the WD repeat coronin family.|||Binds actin. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. http://togogenome.org/gene/10090:Polr2f ^@ http://purl.uniprot.org/uniprot/P61219 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo6/eukaryotic RPB6 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.|||DNA-dependent RNA polymerases catalyze the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2F/RPB6 is part of the clamp element and together with parts of RPB1 and RPB2 forms a pocket to which the RPB4-RPB7 subcomplex binds (By similarity).|||Nucleus http://togogenome.org/gene/10090:Mfsd9 ^@ http://purl.uniprot.org/uniprot/Q8C0T7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Membrane http://togogenome.org/gene/10090:Cyp17a1 ^@ http://purl.uniprot.org/uniprot/P27786|||http://purl.uniprot.org/uniprot/Q3UYU1|||http://purl.uniprot.org/uniprot/Q53YJ1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis. Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol. Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:36640554). Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (By similarity).|||Belongs to the cytochrome P450 family.|||Both 17alpha-hydroxylation and 17,20 lyase activities are significantly stimulated by the presence of cytochrome b5.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Tasp1 ^@ http://purl.uniprot.org/uniprot/Q3UJT0|||http://purl.uniprot.org/uniprot/Q8R1G1 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the Ntn-hydrolase family.|||Intramolecular proteolysis generates 2 subunits, alpha and beta, which reassemble through a non-covalent association to form the fully active enzyme.|||Protease responsible for KMT2A/MLL1 and KMT2D/MLL2 processing and activation (PubMed:16951254). Through substrate activation, it controls the expression of HOXA genes, and the expression of key cell cycle regulators including CCNA1, CCNB1, CCNE1 and CDKN2A (PubMed:16951254).|||Tasp1-null mice are born with no apparent respiratory distress, but the majority dies at postpartum day 1 or 2 with no obvious milk spots, suggesting a feeding defect. Newborns are smaller in size compared to their wild-type littermates. This phenotype appears in utero. Animals that survive the newborn period are markedly smaller through adulthood, and display skeletal abnormalities. http://togogenome.org/gene/10090:Taar7f ^@ http://purl.uniprot.org/uniprot/Q5QD08 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Olfactory receptor activated by trace amine N-methylpiperidine. This receptor is probably mediated by the G(s)-class of G-proteins which activate adenylate cyclase.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Shisa7 ^@ http://purl.uniprot.org/uniprot/Q8C3Q5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shisa family.|||Expressed in the cerebral cortex on 17 dpc and in olfactory bulb and hippocampus on postnatal day 1 (P1) (PubMed:26623514). Expression in hippocampus increases during postnatal development and reaches a plateau after 3 weeks (PubMed:29199957). Expression is high during prenatal development and decreases in the thalamus and brainstem during postnatal development (PubMed:26623514).|||Interacts with GABA(A)R (GABA type A receptor) subunits GABRA1, GABRA2 and GABRG2; the interaction is direct (PubMed:31601770). Does not interact with GABRB2 and GABRB3 subunits (PubMed:31601770). Interacts with AMPAR subunits GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and SHISA7 in heterologous cells (PubMed:26623514, PubMed:29199957). Interacts (via PDZ-binding motif) with DLG4/PSD-95 (via PDZ domain)in heterologous cells; the interaction is direct (PubMed:29199957).|||Knockout mice show a decrease in miniature inhibitory postsynaptic currents frequency, but not amplitude, in CA1 pyramidal neurons (PubMed:31601770). Mice show impaired acquisition of contextual fear memory without affecting auditory fear learning or anxiety (PubMed:29199957). Decreased long-term potentiation of hippocampal glutamatergic synapses (PubMed:29199957).|||Mainly expressed in neurons (PubMed:26623514, PubMed:29199957, PubMed:31601770). Highly expressed in brain structures including cortex, striatum, olfactory bulb, amygdala hippocampus CA1-3 and dentate gyrus (at protein level) (PubMed:26623514, PubMed:29199957, PubMed:31601770).|||N-glycosylated.|||Postsynaptic density membrane|||SHISA7 has been reported to interact with AMPAR subunit GRIA1 in heterologous conditions and in the brain (PubMed:26623514, PubMed:29199957). However, it was later demonstrated that SHISA7 does not colocalize neither interact with AMPAR, but with GABA(A)R (PubMed:31601770). Therefore additional experiments are needed to understand the discrepancy for SHISA7 function.|||The GRID (GABA(A)R-interacting domain) is critical for its subcellular localization and interaction with GABA(A)R.|||The PDZ-binding motif interacts with PDZ-domain of scaffolding protein DLG4 in heterologous cells.|||Transmembrane protein that regulates gamma-aminobutyric acid type A receptor (GABA(A)R) trafficking, channel deactivation kinetics and pharmacology, necessary for fast inhibitory transmission in the brain (PubMed:31601770). Enhances the action of benzodiazepine, a primary GABA(A)Rs target drug, in the brain (PubMed:31601770). May affect channel kinetics of AMPA-type glutamate receptors (AMPAR), the brain's main excitatory neurotransmitter, necessary for synaptic hippocampal plasticity, and memory recall (Probable). May regulate the induction and maintenance of long-term potentiation at Schaffer collaterals/CA3-CA1 excitatory synapses (Probable). http://togogenome.org/gene/10090:Mrpl51 ^@ http://purl.uniprot.org/uniprot/Q9CPY1 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL51 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity). Interacts with OXA1L (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Fhod1 ^@ http://purl.uniprot.org/uniprot/Q6P9Q4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the formin homology family.|||Cytoplasm|||Phosphorylated by ROCK1.|||Regulated by intramolecular binding to a C-terminal auto-inhibitory domain. Effector binding abolishes this interaction and activates the protein (By similarity).|||Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing (By similarity).|||Self-associates via the FH2 domain. Binds to F-actin via its N-terminus. Binds to the cytoplasmic domain of CD21 via its C-terminus (By similarity). Interacts with ROCK1 in a Src-dependent manner (By similarity).|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).|||bleb|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Nudt2 ^@ http://purl.uniprot.org/uniprot/P56380|||http://purl.uniprot.org/uniprot/Q3V1C8 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the Nudix hydrolase family.|||Catalyzes the asymmetric hydrolysis of diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) to yield AMP and ATP (By similarity). Exhibits decapping activity towards FAD-capped RNAs and dpCoA-capped RNAs in vitro (PubMed:32432673).|||Divalent metal ions. http://togogenome.org/gene/10090:Or6n1 ^@ http://purl.uniprot.org/uniprot/Q7TRW1|||http://purl.uniprot.org/uniprot/Q8VFZ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem72 ^@ http://purl.uniprot.org/uniprot/Q8C3K5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pi4ka ^@ http://purl.uniprot.org/uniprot/A0A140T8I9|||http://purl.uniprot.org/uniprot/E9Q3L2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin (By similarity). The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. Interaction with TMEM150A regulates PtdIns(4)P synthesis (By similarity).|||Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate.|||Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.|||Cell membrane|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2). Interacts with TMEM150A; regulating recruitment to the plasma membrane. Interacts with TTC7A.|||Cytoplasm|||Early embryonic lethality. Conditional knockout mice show a dramatic depletion of cellular phosphatidylinositol 4-phosphate (PtdIns(4)P). http://togogenome.org/gene/10090:Ms4a6b ^@ http://purl.uniprot.org/uniprot/Q99N09 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed at high levels in thymus, spleen, and peripheral lymph nodes, with less abundant levels in non-lymphoid tissues.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Tnfsf10 ^@ http://purl.uniprot.org/uniprot/P50592|||http://purl.uniprot.org/uniprot/Q3U5H0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG. Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis.|||Homotrimer.|||Homotrimer. One TNFSF10 homotrimer interacts with three TNFSF10A mononers. One TNFSF10 homotrimer interacts with three TNFSF10B mononers.|||Membrane|||Secreted|||Tyrosine phosphorylated by PKDCC/VLK.|||Widespread. http://togogenome.org/gene/10090:Akip1 ^@ http://purl.uniprot.org/uniprot/Q9JJR5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Enhances NF-kappa-B transcriptional activity by regulating the nuclear localization of the NF-kappa-B subunit RELA and promoting the phosphorylation of RELA by PRKACA. Regulates the effect of the cAMP-dependent protein kinase signaling pathway on the NF-kappa-B activation cascade (By similarity).|||Interacts with PRKACA and RELA.|||Nucleus http://togogenome.org/gene/10090:Dcaf15 ^@ http://purl.uniprot.org/uniprot/Q6PFH3 ^@ Function|||Subunit ^@ Component of the DCX(DCAF15) complex, also named CLR4(DCAF15) complex, composed of DCAF15, DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1.|||Substrate-recognition component of the DCX(DCAF15) complex, a cullin-4-RING E3 ubiquitin-protein ligase complex that mediates ubiquitination and degradation of target proteins. The DCX(DCAF15) complex acts as a regulator of the natural killer (NK) cells effector functions, possibly by mediating ubiquitination and degradation of cohesin subunits SMC1A and SMC3. May play a role in the activation of antigen-presenting cells (APC) and their interaction with NK cells. http://togogenome.org/gene/10090:Cib2 ^@ http://purl.uniprot.org/uniprot/Q9Z309 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis (PubMed:23023331, PubMed:29084757, PubMed:29255404, PubMed:28663585, PubMed:34089643). Acts as a auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells (PubMed:34089643). Essential for mechanoelectrical transduction (MET) currents in auditory hair cells and thereby required for hearing (PubMed:29084757, PubMed:29255404, PubMed:28663585). Regulates the function of hair cell mechanotransduction by controlling the distribution of transmembrane channel-like proteins TMC1 and TMC2, and by regulating the function of the MET channels in hair cells (PubMed:34089643). Required for the maintenance of auditory hair cell stereocilia bundle morphology and function and for hair-cell survival in the cochlea (PubMed:29084757, PubMed:29255404, PubMed:28663585). Critical for proper photoreceptor cell maintenance and function (PubMed:23023331). Plays a role in intracellular calcium homeostasis by decreasing ATP-induced calcium release (PubMed:23023331). Seems to be dispensable for vestibular functions (PubMed:29084757).|||Causes profound hearing loss, whereas balance and retinal functions appear normal (PubMed:29255404, PubMed:29084757). Impaired stereocilia development in hair cells (PubMed:29255404). Abolished mechanoelectrical transduction (MET) currents in auditory hair cells; while unchanged in vestibular hair cells (PubMed:29255404). Hair bundle morphological abnormalities begin after birth, with regression of the stereocilia and rapid hair-cell death (PubMed:29084757). At P6-P7, the rounded horseshoe-shape bundles at the base of the cochlea lack their typical V-shape (PubMed:29084757). At P7, disorganization of stereocilia in outer hair cells (OHC), with fragmentation in some stereocilia bundles and stereocilia in the shortest row are heterogeneous in length (PubMed:29255404, PubMed:29084757). The inner hair cell (IHC) hair bundles at the cochlear base exhibit an abnormal wavy shape, but, unlike OHCs, all the stereocilia within the same row are of the same length (PubMed:29084757). At P8, the second row of OHC stereocilia are over-grown to the height close to the first row, whereas the third row are largely retracted, resulting in the loss of their staircase architecture (PubMed:29255404). In IHC, the kinocilium is not retracted properly at P8 (PubMed:29255404). On P9, most OHCs have discontinuous horseshoe-like shaped hair bundles, due to the loss of the centrally located stereocilia at the vertex of the bundle (PubMed:29084757). Many IHC bundles at this terminal mature stage still retain their kinocilia, whereas the wild-type IHCs loose this structure at post-hearing onset (beyond P14) stages (PubMed:29084757). On P18, the short row stereocilia have almost entirely disappeared in both IHC and OHC hair bundles, whereas those in the middle row are much shorter than usual, with some missing entirely (PubMed:29084757). At P20, apoptotic hair cells in the cochlea are detected (PubMed:29084757). At P30, disorganization of stereocilia is increased, with complete loss of stereocilia in some animals and other morphological abnormalities, such as stereocilia fusion (PubMed:29255404). On P90 and P120, only sporadic fused stereocilia or residual knoblike protrusions are observed on some of the remaining IHC stereociliary bundles of the mid-basal cochlea (PubMed:29084757). Near-complete loss of IHC and OHC bundles on P120 (PubMed:29084757).|||Cytoplasm|||Expressed in inner and outer segments of photoreceptor cells, as well as in the pigmented epithelium. Also observed in the inner and outer plexiform layers and in the ganglion cell layer (at protein level) (PubMed:23023331). Expressed in sensory hair cell stereocilia, with expression mainly at the basal body of the kinocilium and in the hair bundle stereocilia; and the apical surface of hair cells (at protein level) (PubMed:29084757). Located in the tip region of the stereocilia and at the apical surface of hair cells around the cuticular plate (at protein level) (PubMed:29084757). Not expressed in the hair bundles of the vestibular hair cells (PubMed:29084757). Strongly expressed in skeletal muscles, brain, kidney and liver (PubMed:23023331, PubMed:29255404). Expressed in the skeletal muscle, retina and cochlea (PubMed:18611855, PubMed:23023331). Expressed in megakaryocytes and endothelial cells (PubMed:18989529). Expressed in heart, spleen, lung, and inner ear (PubMed:29255404). In the inner ear, expressed in the vestibule, basilar membrane and spiral ganglion cells (PubMed:29255404). Expressed in the supporting cells in both the organ of Corti and the vestibular sensory epithelia (PubMed:23023331).|||Expressed in the central nervous system and in muscle at 16 dpc and onward (PubMed:18611855). Expressed in the inner ear and retina at 15.5 and 17.5 dpc (PubMed:23023331). Detected in stereocilia of cochlear hair cells at P12 and as early as P5 (at protein level) (PubMed:28663585). At P12, expressed in stereocilia and at the tips of surrounding microvilli of the auditory hair cells (at protein level) (PubMed:28663585). At P12 in the inner hair cells, distributed along the length of stereocilia and accumulated at the tips of the shortest, but still mechanotransducing, stereocili (at protein level) (PubMed:28663585). At P12 in the outer hair cells (OHCs), punctate labeling along the length of stereocilia, including labeling at the very tips of OHC stereocilia (at protein level) (PubMed:28663585).|||Monomer (By similarity). Homodimer (By similarity). Interacts with WHRN and MYO7A (By similarity). Interacts with ITGA2B (via C-terminus cytoplasmic tail region); this interaction is stabilized/increased in a calcium and magnesium-dependent manner (PubMed:18611855). Interacts with ITGA7 (via C-terminus cytoplasmic tail region); this interaction is stabilized/increased in a calcium and magnesium-dependent manner (PubMed:18989529). Interacts with TMC1 (PubMed:28663585, PubMed:34089643). Interacts with TMC2 (PubMed:28663585).|||Photoreceptor inner segment|||The binding of either calcium or magnesium significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form).|||photoreceptor outer segment|||sarcolemma|||stereocilium http://togogenome.org/gene/10090:Ifi44 ^@ http://purl.uniprot.org/uniprot/Q8BV66 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IFI44 family.|||Cytoplasm|||This protein aggregates to form microtubular structures. http://togogenome.org/gene/10090:Npsr1 ^@ http://purl.uniprot.org/uniprot/A1KXK3|||http://purl.uniprot.org/uniprot/Q8BZP8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.|||Cell membrane|||G-protein coupled receptor for neuropeptide S (NPS). Promotes mobilization of intracellular Ca(2+) stores. Inhibits cell growth in response to NPS binding. Involved in pathogenesis of asthma and other IgE-mediated diseases.|||Increased expression in lung after ovalbumin induction in a mouse model of ovalbumin-induced lung inflammation.|||Membrane http://togogenome.org/gene/10090:Lcorl ^@ http://purl.uniprot.org/uniprot/Q3U285 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed predominantly in the spermatocytes of the testis. Also found in the kidney, liver and heart.|||May act as transcription activator that binds DNA elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'. May play a role in spermatogenesis.|||Nucleus http://togogenome.org/gene/10090:Thsd1 ^@ http://purl.uniprot.org/uniprot/Q9JM61 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endosome membrane|||Expressed in cerebral vascular endothelium.|||Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.|||Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL. Interacts with TLN1.|||Some animals develop hydrocephalus as early as 8 weeks after birth. A few die spontaneously at 9 weeks and have diffuse cerebral hemorrhage not seen in wild-type littermates.|||focal adhesion http://togogenome.org/gene/10090:Tmem230 ^@ http://purl.uniprot.org/uniprot/Q8CIB6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM134/TMEM230 family.|||Early endosome|||Involved in trafficking and recycling of synaptic vesicles.|||Late endosome|||Membrane|||Recycling endosome|||Widely expressed, including dopaminergic neurons in the substantia nigra.|||autophagosome|||synaptic vesicle|||trans-Golgi network http://togogenome.org/gene/10090:Trim25 ^@ http://purl.uniprot.org/uniprot/Q3TU94|||http://purl.uniprot.org/uniprot/Q61510 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ISGylated.|||Cytoplasm|||Forms homodimers (By similarity). Interacts (via SPRY domain) with RIGI (via CARD domain). Interacts with ZFHX3. Interacts with NLRP12; this interaction reduces the E3 ubiquitin ligase TRIM25-mediated 'Lys-63'-linked RIGI activation. Interacts with the KHDC3L/FILIA-OOEP/FLOPED scaffold complex and BLM at DNA replication forks (PubMed:29125140). Interacts with RTN3; this interaction prevents RIGI ubiquitination (By similarity).|||Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of RIGI and IFIH1. Mediates 'Lys-63'-linked polyubiquitination of the RIGI N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection. Mediates 'Lys-63'-linked polyubiquitination of IFIH1. Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs. Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (By similarity). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (PubMed:29125140). Plays an essential role in the antiviral activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the replication of certain viruses. Mechanistically, mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1 that is required for its optimal binding to target mRNA. Mediates also the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (By similarity).|||Nucleus|||Stress granule|||The C-terminal B30.2/SPRY domain interacts with the first N-terminal CARD domain of RIGI.|||The RING-type zinc finger is important for ISG15 E3 ligase activity and autoISGylation. AutoISGylation negatively regulates ISG15 E3 ligase activity.|||Ubiquitous. http://togogenome.org/gene/10090:Rgl2 ^@ http://purl.uniprot.org/uniprot/Q61193 ^@ Function|||Subunit ^@ Interacts with SAMD9.|||Probable guanine nucleotide exchange factor. Putative effector of Ras and/or Rap. Associates with the GTP-bound form of Rap 1A and H-Ras in vitro. http://togogenome.org/gene/10090:Cfap97d2 ^@ http://purl.uniprot.org/uniprot/G3UW36 ^@ Similarity|||Tissue Specificity ^@ Belongs to the CFAP97 family.|||Expressed in a number of tissues including brain, thymus, lung, heart, liver, spleen, kidney and testis. http://togogenome.org/gene/10090:Zfpm1 ^@ http://purl.uniprot.org/uniprot/O35615 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FOG (Friend of GATA) family.|||First expressed in two extraembryonic mesodermal derivatives, the yolk sac and the allantois in 8.5 dpc embryos. Localized to the embryonic red blood cells within the yolk sac blood islands.|||Interacts with the N-terminal zinc-finger of GATA1, GATA2 and GATA3. Interacts with corepressor CTBP2; this interaction is however not essential for corepressor activity in erythropoiesis. Interacts with TACC3.|||Mainly expressed in hematopoietic tissues. Expressed in the spleen, a primary site of hematopoiesis in the adult mouse, as well as in the liver and testis, but not in the heart, brain, lung, kidney, or skeletal muscle. Among hematopoietic cell lines, it is strongly expressed in erythroid and megakaryocytic cell lines. Expressed at low level in several lymphoid and early myeloid cell lines. Not expressed in mast cell and macrophage lines. Expressed in the heart, where it colocalizes with GATA4, GATA5 and GATA6.|||Nucleus|||The CCHC FOG-type zinc fingers 1, 2, 3 and 5 bind directly to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is essential for the interaction with GATA-type zinc fingers.|||Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA1, GATA2 and GATA3. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. The heterodimer formed with GATA proteins is essential to activate expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, while it represses expression of KLF1. May be involved in regulation of some genes in gonads. May also be involved in cardiac development, in a non-redundant way with ZFPM2/FOG2. http://togogenome.org/gene/10090:Dynlt5 ^@ http://purl.uniprot.org/uniprot/A2AIZ4|||http://purl.uniprot.org/uniprot/B7ZNE0|||http://purl.uniprot.org/uniprot/Q9D5I4 ^@ Similarity|||Subunit ^@ Belongs to the dynein light chain Tctex-type family.|||Interacts with ZMYND10. http://togogenome.org/gene/10090:Ank3 ^@ http://purl.uniprot.org/uniprot/G3X971|||http://purl.uniprot.org/uniprot/G5E8K2|||http://purl.uniprot.org/uniprot/G5E8K3|||http://purl.uniprot.org/uniprot/G5E8K5|||http://purl.uniprot.org/uniprot/S4R2K9 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in many epithelial tissues, muscles and axons. Expressed in kidney, brain, skin, lung, liver, intestine, pancreas, heart and testis (at protein level). In testis, expressed in Leydig cells, but very weakly or not at all in Sertoli cells or seminiferous tubules. Expressed in macrophages (at protein level).|||In an in vitro model of myogenesis, not detected in proliferating myoblasts. Hardly detectable during the first days of differentiation. Expression greatly increases in mature myotubes.|||Lysosome|||May be a constituent of a NFASC/NRCAM/ankyrin G complex. Interacts with RHBG (By similarity). Directly interacts with DMD and betaDAG1; this interaction does not interfere with DMD-binding and is required for DMD and betaDAG1 retention at costameres. Interacts (via N-terminal ANK repeats) with SCHIP1 isoform 7 (via C-terminus); this interaction is required for the localization at axon initial segments (AISs) and nodes of Ranvier (NRs). Interacts with PLEC and FLNC (By similarity). Interacts with KCNA1; this inhibits channel activity (PubMed:23903368). Interacts with SCN5A (By similarity).|||Membrane|||Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (By similarity). In skeletal muscle, required for costamere localization of DMD and betaDAG1. Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368).|||Postsynaptic cell membrane|||T-tubule|||Up-regulated by high dietary Mg(2+) levels.|||axon|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Sco2 ^@ http://purl.uniprot.org/uniprot/Q8VCL2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCO1/2 family.|||Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). Involved in transporting copper to the Cu(A) site on MT-CO2/COX2. Also acts as a thiol-disulfide oxidoreductase to regulate the redox state of the cysteines in SCO1 during maturation of MT-CO2/COX2.|||Expressed in retina, retinal pigment epithelium, and sclera.|||Homodimer. Interacts with COA6. Found in a complex with TMEM177, COX20, COA6, MT-CO2/COX2, COX18 and SCO1. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20 in a MT-CO2/COX2- and COX18-dependent manner. Interacts with COX16.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Calml3 ^@ http://purl.uniprot.org/uniprot/Q9D6P8 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the calmodulin family.|||Binds four calcium ions.|||Interacts with MYO10, the interaction is calcium-dependent and essential for MYO10 function in filopodial extension.|||May function as a specific light chain of unconventional myosin-10 (MYO10), also enhances MYO10 translation, possibly by acting as a chaperone for the emerging MYO10 heavy chain protein. May compete with calmodulin by binding, with different affinities, to cellular substrates (By similarity). http://togogenome.org/gene/10090:Lrrc32 ^@ http://purl.uniprot.org/uniprot/G3XA59 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRC32/LRRC33 family.|||Cell membrane|||Cell surface|||Interacts with TGFB1; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1 (By similarity). Interacts with TGFB2 (By similarity). Interacts with TGFB3; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB3, leading to regulate activation of TGF-beta-3 (PubMed:28912269). Interacts with LAPTM4B; decreases TGFB1 production in regulatory T-cells (By similarity).|||Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space (PubMed:25127859). Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (PubMed:25127859, PubMed:28912269). Able to outcompete LTBP1 for binding to LAP regulatory chain of TGF-beta (By similarity). Controls activation of TGF-beta-1 (TGFB1) on the surface of activated regulatory T-cells (Tregs) (PubMed:25127859). Required for epithelial fusion during palate development by regulating activation of TGF-beta-3 (TGFB3) (PubMed:28912269).|||Lethality within 24 hours after birth (PubMed:28912269). Mice display defective palatogenesis without apparent abnormalities in other major organs (PubMed:28912269).|||Present in medial edge epithelial cells at 14.5 dpc (at protein level). http://togogenome.org/gene/10090:H2bl1 ^@ http://purl.uniprot.org/uniprot/Q9D9Z7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the histone H2B family.|||Cytoplasm|||Highly expressed during late spermiogenesis, in condensing spermatids (at protein level). Expression persists in mature spermatozoa (at protein level). Expression is first detected from the round spermatid stage and increases thereafter.|||May act as an acrosome-nuclear docking protein in sperm.|||Present in testis (at protein level) (PubMed:11784042, PubMed:17261847). Not detected in other tissues tested (PubMed:17261847). http://togogenome.org/gene/10090:Ctsf ^@ http://purl.uniprot.org/uniprot/Q9R013 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C1 family.|||Lysosome|||Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis. http://togogenome.org/gene/10090:Adap2 ^@ http://purl.uniprot.org/uniprot/Q8R2V5 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Cytoplasm|||GTPase-activating protein for the ADP ribosylation factor family (Potential). Binds phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4). Possesses a stoichiometry of two binding sites for InsP4 with identical affinity (By similarity). http://togogenome.org/gene/10090:Pigt ^@ http://purl.uniprot.org/uniprot/Q8BXQ2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGT family.|||Component of the GPI transamidase complex. Essential for transfer of GPI to proteins, particularly for formation of carbonyl intermediates (By similarity).|||Endoplasmic reticulum membrane|||Forms a complex with PIGK/GPI8, PIGS, PIGU and GPAA1/GAA1. Has a critical role in maintaining the complex by stabilizing the expression of GPAA1 and GPI8 and linking them to PIGS (By similarity).|||The disulfide bond between PIGK/GPI8 and PIGT is important for normal enzyme activity. http://togogenome.org/gene/10090:Adam20 ^@ http://purl.uniprot.org/uniprot/Q7M763 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Decr2 ^@ http://purl.uniprot.org/uniprot/Q3UVJ7|||http://purl.uniprot.org/uniprot/Q9WV68 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxiliary enzyme of beta-oxidation. Participates in the degradation of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in peroxisome. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA. Has activity towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA, suggesting that it does not constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.|||Monomer, dimer and oligomer.|||Peroxisome http://togogenome.org/gene/10090:Hmgcr ^@ http://purl.uniprot.org/uniprot/Q01237|||http://purl.uniprot.org/uniprot/Q8BV96 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HMG-CoA reductase family.|||Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis.|||Endoplasmic reticulum membrane|||Homotetramer. Homodimer. Interacts (via its SSD) with INSIG1; the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with UBIAD1.|||Homozygous knockout mice show early embryonic lethality.|||N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner.|||Peroxisome membrane|||Phosphorylated. Phosphorylation at Ser-871 reduces the catalytic activity.|||Regulated by a negative feedback mechanism through sterols and non-sterol metabolites derived from mevalonate (By similarity). Phosphorylation at Ser-871 down-regulates the catalytic activity (By similarity).|||Undergoes sterol-mediated ubiquitination and ER-associated degradation (ERAD). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1 or INSIG2. The INSIG1 binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78, RNF139 or RNF145, initiating ubiquitination of the reductase. The ubiquitinated reductase is then extracted from the ER membrane and delivered to cytosolic 26S proteosomes by a mechanism probably mediated by the ATPase Valosin-containing protein VCP/p97. The INSIG2-binding leads to the recruitment of the ubiquitin ligase RNF139, initiating ubiquitination of the reductase. Lys-248 is the main site of ubiquitination. Ubiquitination is enhanced by the presence of a geranylgeranylated protein. http://togogenome.org/gene/10090:Mib1 ^@ http://purl.uniprot.org/uniprot/Q80SY4 ^@ Developmental Stage|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Chimeric cDNA.|||Contaminating sequence. Sequence of unknown origin in the C-terminal part.|||Cytoplasm|||Detected in all tissues tested. Present in embryo, embryonic stem cells, bladder, skeletal muscle, bladder, uterus, testis, stomach, colon, ileum, trachea, lung, aorta, kidney, spleen, liver and vas deferens (at protein level). Highly expressed in testis.|||E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation (By similarity). Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis.|||Highly expressed both in embryos and adult tissues. In 9.5 dpc and 10.5 dpc embryos, it is expressed in the tail bud, limb buds and somites. Expressed in the same pattern than MIB2 in the skin and intestine at postnatal day 1 (P1) and in the hair follicle in the skin in the adult.|||Interacts with CEP131 and PCM1.|||Ubiquitinated; this modification is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock (By similarity). Ubiquitinated; possibly via autoubiquitination.|||centriolar satellite http://togogenome.org/gene/10090:Atp1a3 ^@ http://purl.uniprot.org/uniprot/Q6PIC6|||http://purl.uniprot.org/uniprot/Q8R0E8|||http://purl.uniprot.org/uniprot/Q8VCE0 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with regulatory subunit FXYD1.|||This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (By similarity). http://togogenome.org/gene/10090:Tmem255a ^@ http://purl.uniprot.org/uniprot/Q8BHS0|||http://purl.uniprot.org/uniprot/Q8BHW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM255 family.|||Membrane http://togogenome.org/gene/10090:Jmy ^@ http://purl.uniprot.org/uniprot/A0A0R4J0V4|||http://purl.uniprot.org/uniprot/Q9QXM1 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates in DNA-damaged cells (at protein level).|||Acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions. In nucleus, acts as a cofactor that increases p53/TP53 response via its interaction with p300/EP300. Increases p53/TP53-dependent transcription and apoptosis, suggesting an important role in p53/TP53 stress response such as DNA damage. In cytoplasm, acts as a nucleation-promoting factor for both branched and unbranched actin filaments. Activates the Arp2/3 complex to induce branched actin filament networks. Also catalyzes actin polymerization in the absence of Arp2/3, creating unbranched filaments. Contributes to cell motility by controlling actin dynamics. May promote the rapid formation of a branched actin network by first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments. Upon nutrient stress, directly recruited by MAP1LC3B to the phagophore membrane surfaces to promote actin assembly during autophagy (By similarity). The p53/TP53-cofactor and actin activator activities are regulated via its subcellular location.|||Alters the p53/TP53 response.|||Belongs to the JMY family.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasmic vesicle|||Endomembrane system|||Interacts with p300/EP300, the complex activates p53/TP53 transcriptional activity (PubMed:11511361, PubMed:10518217). Interacts with TTC5/STRAP; the interaction takes place in the nucleus and facilitates the association between JMY and p300/EP300 (PubMed:11511361). Interacts with TTC5/STRAP; the interaction takes place in the cytoplasm and results in the inhibition of JYM's nucleation activity (By similarity). Interacts with MAP1LC3B; the interaction results in the activation of JYM's nucleation activity in the cytoplasm (By similarity).|||Membrane|||Nucleus|||The N-terminal region is involved in actin binding and actin nucleation activity.|||Ubiquitinated by MDM2, leading to its subsequent degradation by the proteasome. In case of DNA damage, the interaction with MDM2 is altered, preventing degradation and allowing interaction with p300/EP300 and its function in p53/TP53 stress response.|||Widely expressed, except in testis where it is expressed at low level.|||autophagosome membrane|||cytoskeleton http://togogenome.org/gene/10090:Gpr119 ^@ http://purl.uniprot.org/uniprot/Q7TQP3 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expression restricted to the beta-cells of pancreatic islets.|||Receptor for the endogenous fatty-acid ethanolamide oleoylethanolamide (OEA) and lysophosphatidylcholine (LPC). Functions as a glucose-dependent insulinotropic receptor. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Seems to act through a G(s) mediated pathway.|||Up-regulated in islets of obese hyperglycemic db/db mice. http://togogenome.org/gene/10090:Prkaa2 ^@ http://purl.uniprot.org/uniprot/Q8BRK8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity). Interacts with DUSP29 (PubMed:30201684).|||Activated by phosphorylation on Thr-172. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172. ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-172, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (By similarity). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (By similarity). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (By similarity). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:15331533, PubMed:15561936). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (PubMed:16804075, PubMed:16804077). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:21454484, PubMed:20647423, PubMed:21459323, PubMed:17609368). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (PubMed:16148943, PubMed:16308421). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (PubMed:20647423). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:18439900, PubMed:21258367, PubMed:21205641, PubMed:32912901). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (By similarity). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (By similarity). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21258367, PubMed:21205641). In that process also activates WDR45/WIPI4 (By similarity). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (PubMed:19833968). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (PubMed:20361929). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (By similarity). Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (PubMed:23332761). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (PubMed:23332761).|||Cytoplasm|||Mice develop obesity when animals are fed a high-fat diet, as a result of an enhanced lipid accumulation in pre-existing adipocytes but not in other tissues.|||Nucleus|||Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1) (By similarity).|||The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity.|||Ubiquitinated. http://togogenome.org/gene/10090:Cycs ^@ http://purl.uniprot.org/uniprot/P62897|||http://purl.uniprot.org/uniprot/Q56A15 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome c family.|||Binds 1 heme c group covalently per subunit.|||Binds 1 heme group per subunit.|||Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.|||Found in embryos and in adult liver and heart.|||Mitochondrion intermembrane space|||Phosphorylation at Tyr-49 and Tyr-98 both reduce by half the turnover in the reaction with cytochrome c oxidase, down-regulating mitochondrial respiration.|||Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases. http://togogenome.org/gene/10090:Krt1 ^@ http://purl.uniprot.org/uniprot/P04104 ^@ Developmental Stage|||Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cell membrane|||Cytoplasm|||Defects in Krt1 are a cause of epidermolytic hyperkeratosis (EHK); also known as bullous congenital ichthyosiform erythroderma (BIE). EHK is a hereditary skin disorder characterized by intraepidermal blistering, a marked thickening of the stratum corneum, pigmentation of the skin and erosions at sites of trauma which are all present from birth.|||Expressed in the infundibular regions of the ear, the interfollicular epidermis of the back, in the interscale regions containing hair follicles in the tail, and in the soles of the footpads (at protein level).|||Expressed in the skin at birth.|||Heterotetramer of two type I and two type II keratins (PubMed:24940650, PubMed:11408584). Heterodimer with KRT10 (PubMed:24940650). Two heterodimers of KRT1 and KRT10 form a heterotetramer (By similarity). Forms a heterodimer with KRT14; the interaction is more abundant in the absence of KRT5 (PubMed:11408584). Interacts with PLEC isoform 1C, when in a heterodimer with KRT10 (PubMed:24940650). Interacts with ITGB1 in the presence of RACK1 and SRC, and with RACK1 (By similarity). Interacts with C1QBP; the association represents a cell surface kininogen receptor (By similarity). Interacts with EPPK1; interaction is dependent of higher-order structure of intermediate filament (By similarity).|||May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||Undergoes deimination of some arginine residues (citrullination). http://togogenome.org/gene/10090:Calr ^@ http://purl.uniprot.org/uniprot/B2MWM9|||http://purl.uniprot.org/uniprot/P14211 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with PDIA3 through the tip of the extended arm formed by the P-domain.|||Belongs to the calreticulin family.|||Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (PubMed:20880849, PubMed:21652723). Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export (By similarity). Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity). Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and might participate in the block to polyspermy (By similarity).|||Can be divided into a N-terminal globular domain, a proline-rich P-domain forming an elongated arm-like structure and a C-terminal acidic domain. The P-domain binds one molecule of calcium with high affinity, whereas the acidic C-domain binds multiple calcium ions with low affinity (By similarity).|||Cell surface|||Cortical granule|||Cytolytic granule|||Endoplasmic reticulum lumen|||Monomer. Interacts with GABARAP, NR3C1, PDIA3/ERp57 and TRIM21. Interacts (via P-domain) with PDIA5 (By similarity). Interacts with PPIB (PubMed:20801878). Interacts with SPACA9 (PubMed:24256100). Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (PubMed:16931514). Interacts with CLCC1 (By similarity).|||Sarcoplasmic reticulum lumen|||The interaction with glycans occurs through a binding site in the globular lectin domain.|||The zinc binding sites are localized to the N-domain.|||cytosol|||extracellular matrix http://togogenome.org/gene/10090:Cox19 ^@ http://purl.uniprot.org/uniprot/Q8K0C8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COX19 family.|||Interacts with CHCHD4/MIA40 forming transient intermolecular disulfide bridges.|||Mitochondrion|||Mitochondrion intermembrane space|||Required for the transduction of an SCO1-dependent redox signal from the mitochondrion to ATP7A to regulate cellular copper homeostasis. May be required for the assembly of mitochondrial cytochrome c oxidase.|||cytosol http://togogenome.org/gene/10090:Homer1 ^@ http://purl.uniprot.org/uniprot/Q3UVL6|||http://purl.uniprot.org/uniprot/Q5D052|||http://purl.uniprot.org/uniprot/Q9Z2Y3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Homer family.|||Cytoplasm|||Isoform 1, isoform 3 and isoform 5 are expressed in skeletal muscle at the level of the Z line, in heart, forebrain and cerebellum. Isoform 2, is a minor isoform and is expressed in cardiac and skeletal muscle. Isoform 5 is expressed in the postsynaptic region of neurons.|||Postsynaptic density|||Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Isoform 1 regulates the trafficking and surface expression of GRM5. Differentially regulates the functions of the calcium activated channel ryanodine receptors RYR1 and RYR2. Isoform 1 decreases the activity of RYR2, and increases the activity of RYR1, whereas isoform 5 counteracts the effects by competing for binding sites. Isoform 3 regulates the trafficking and surface expression of GRM5. Isoform 5 acts as a natural dominant negative, in dynamic competition with constitutively expressed isoform 1, isoform 2 and isoform 3 to regulate synaptic metabotropic glutamate function. Isoform 5, may be involved in the structural changes that occur at synapses during long-lasting neuronal plasticity and development (By similarity). Forms a high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (By similarity).|||Synapse|||Tetramer; this tetrameric structure is critical for forming the high-order complex with SHANK1, which in turn is necessary for the structural and functional integrity of dendritic spines (By similarity). Isoform 1, isoform 2 and isoform 3 encode a coiled-coil structure that mediates homo- and heteromultimerization (By similarity). Interacts with GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2 and SHANK3 (PubMed:12379179, PubMed:21558424, PubMed:24153177). Interacts with IFT57 and OPHN1 (PubMed:17107665). Interacts with SHANK1; forms high-order polymerized complex with a mesh-like network structure, at least composed of SHANK1, HOMER1 and DLGAP1; the complex formation is SHANK1 multimerization dependent (By similarity). Interacts with NFATC4 (By similarity). Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA (By similarity). Interacts with SRGAP2 (PubMed:27373832).|||The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. The coiled-Coil domain forms an antiparallel tetrameric arrangement (By similarity).|||dendritic spine http://togogenome.org/gene/10090:Thnsl1 ^@ http://purl.uniprot.org/uniprot/Q149D1|||http://purl.uniprot.org/uniprot/Q8BH55 ^@ Similarity ^@ Belongs to the threonine synthase family. http://togogenome.org/gene/10090:Lrp11 ^@ http://purl.uniprot.org/uniprot/Q8CB67 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the LDLR family.|||Membrane http://togogenome.org/gene/10090:Ociad1 ^@ http://purl.uniprot.org/uniprot/Q9CRD0 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Asrij' stands for 'blood' in Sanskrit as this protein is strongly expressed in blood vessels.|||Belongs to the OCIAD1 family.|||Endosome|||Expressed at high levels in the brain and at lower levels in the heart, ovary, testis and kidney. Expression is strongest in embryonic stem cells and in the blood vessels.|||Expression is down-regulated as differentiation proceeds in stem cells.|||First detected at 6.5 dpc in the primitive streak region of the epiblast and extraembryonic vasculature. Expression in the 8.5 dpc yolk sac is seen within blood islands and the capillary plexus. As embryogenesis proceeds, expression becomes prominent in the blood islands and the primitive blood vessels of the yolk sac. By 8-8.5 dpc, a more generalized expression pattern is seen in the neural folds and caudally in the presomitic mesoderm and primitive streak regions. A definite increase in vascular expression is seen in the embryo by 9.5 dpc. Tissue-specific expression is initially seen from early 9.5 dpc in the anterior-most regions of the head, mainly in the optic vesicle and branchial arches. At 11.5 dpc and 13.5 dpc, strong expression is seen in the embryonic stem cells of the blood vessels, especially in the capillaries of the brain and in the hyaline vasculature of the eye. Weak expression is also seen in the lingual vessels and in the neural crest-derived regions of the jaw. A rapid increase in expression in the trunk is seen between 9.5 dpc and 10.5 dpc and by 13.5 dpc, expression is more localized. Expression is not detected in the embryonic heart at early 9.5 dpc and from 11.5 dpc onward, increasing expression is seen in the atrium, ventricle, and outflow tracts of the heart.|||Interacts with STAT3.|||Maintains stem cell potency (PubMed:23972987). Increases STAT3 phosphorylation and controls ERK phosphorylation (PubMed:23972987). May act as a scaffold, increasing STAT3 recruitment onto endosomes (PubMed:23972987).|||The OCIA domain is necessary and sufficient for endosomal localization (PubMed:23972987). http://togogenome.org/gene/10090:Ergic2 ^@ http://purl.uniprot.org/uniprot/Q9CR89 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ERGIC family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||May form a heteromeric complex composed of ERGIC1, ERGIC2 and ERGIC3 (By similarity). Interacts with ERGIC3, the interaction is required for the stable expression of both proteins (By similarity). May interact with EEF1A1 (By similarity).|||Nucleus|||Possible role in transport between endoplasmic reticulum and Golgi.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Fxn ^@ http://purl.uniprot.org/uniprot/O35943|||http://purl.uniprot.org/uniprot/Q3TV21 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the frataxin family.|||Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer (By similarity). Homodimer. Monomer (probable predominant form). Oligomer (PubMed:11823441). Monomers and polymeric aggregates of >1 MDa have been isolated from mitochondria. A small fraction of heterologous overexpressed recombinant frataxin forms high-molecular weight aggregates that incorporate iron. Interacts with LYRM4. Interacts (via ferrous form) with ISCU; the interaction is possible when both are bound to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) and the interaction enhances FXN interaction to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) (By similarity). Interacts with FECH; one iron-bound FXN monomer seems to interact with a FECH homodimer. Interacts with SDHA and SDHB (By similarity). Interacts with ACO2; the interaction is dependent on citrate (By similarity). Interacts with HSPA9 (By similarity). Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (PubMed:21298097, PubMed:25597503).|||Expression in the ventricular zone which corresponds to dividing neuronal precursors begins at day 12.5, increases during embryonic development and persists at postnatal day 7 (P7) in the ependymal layer, which is the remnant of the ventricular zone. Weak expression seen in the spinal cord and medulla oblongata, starting at 14.5 dpc and expression also observed in dorsal root ganglia, starting at 14.5 dpc. At P14, expression in the dorsal root ganglia is restricted to the cortical region where the sensory neuron cell bodies are located. In non-neural tissues strong expression seen in the developing liver from 10.5 dpc. Expression detected in the heart and in the cortex of the developing kidney at 12.5 dpc and later. Very high expression observed in the brown adipose tissue. Expression seen in small islands around the neck and back at 14.5 dpc, then in large masses at 16.5 dpc and 18.5 dpc and at P14 is absent in brown adipose tissue. Expression also seen in the thymus and developing gut at 14.5 dpc and until postnatal life. At P14, expression in thymus is restricted to the proliferating cells in the cortical zone and is also prominent in the spleen. Found in the lung at 14.5 dpc.|||Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:25597503, PubMed:19805308). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:25597503). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity. May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems. May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation. May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (By similarity).|||Heart, liver, skeletal muscle, kidney, spleen and thymus. Weakly expressed in the brain and lung.|||Interacts with ACO1. Interacts with ISCU (cytoplasmic form).|||Loss of cell division and lethal in fibroblasts.|||Mitochondrion|||Modulates the RNA-binding activity of ACO1. May be involved in the cytoplasmic iron-sulfur protein biogenesis. May contribute to oxidative stress resistance and overall cell survival.|||Processed in two steps by mitochondrial processing peptidase (MPP). MPP first cleaves the precursor to intermediate form and subsequently converts the intermediate to yield frataxin mature form (frataxin(81-210)) which is the predominant form. The additional forms, frataxin(56-210) and frataxin(78-210), seem to be produced when the normal maturation process is impaired; their physiological relevance is unsure.|||cytosol http://togogenome.org/gene/10090:Fiz1 ^@ http://purl.uniprot.org/uniprot/Q9WTJ4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in the retina at 14.5 dpc.|||Interacts with FLT3 cytoplasmic catalytic domain, following receptor stimulation, in a kinase-independent manner. Does not interact with other structurally related receptor tyrosine kinases, including KIT, CSF1R and PDGFR. Interacts with NRL (By similarity).|||May be a transcriptional repressor of NRL function in photoreceptors. Does not repress CRX-mediated transactivation (By similarity).|||Nucleus|||Widely expressed. In the retina, highest expression in the ganglion cell layer. http://togogenome.org/gene/10090:Or52e2 ^@ http://purl.uniprot.org/uniprot/Q8VGV8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Myom1 ^@ http://purl.uniprot.org/uniprot/Q62234 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer. Interacts with TTN/titin and PNKD (By similarity).|||M line|||May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle. May also contact myosin filaments. Also binds beta-integrins.|||Ubiquitously expressed in all striated muscles. Expressed in all fiber types. http://togogenome.org/gene/10090:Tas2r114 ^@ http://purl.uniprot.org/uniprot/Q7M722 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Lhx1 ^@ http://purl.uniprot.org/uniprot/P63006|||http://purl.uniprot.org/uniprot/Q569N5 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in both embryos and adults.|||In mid to late stage embryos, expressed in a restricted region of mesoderm in the primitive streak. At 7.5 days, expressed in a horseshoe shape at the periphery of the node, as well as along both sides of the adjacent notochord. Also present in presumptive lateral and intermediate mesoderm. Later, expression become progressively restricted to intermediate mesoderm, and the developing excretory system including the pronephric region, mesonephros, nephric duct and metanephros. In the metanephros, strongly expressed in renal vesicles and S-shaped and coma-shaped bodies, as well as in the ureteric bud and its derivatives. Also expressed in the dorsal root ganglia. By stage 10.5, also expressed in regions of the central nervous system in the telencephalon through to the spinal cord. In adults, expressed in the cerebellum/medulla and kidney, and at very low levels in the cerebrum.|||Interacts with LDB1 via the tandem LIM domains.|||Nucleus|||Potential transcription factor. May play a role in early mesoderm formation and later in lateral mesoderm differentiation and neurogenesis.|||The LIM domains exert a negative regulatory function and disruption of the LIM domains produces an activated form. In addition, two activation domains and a negative regulatory domain exist C-terminally to the homeobox (By similarity). http://togogenome.org/gene/10090:Slc29a2 ^@ http://purl.uniprot.org/uniprot/Q61672 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.|||Bidirectional uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:11085929). Functions as a Na(+)-independent, passive transporter (By similarity). Involved in the transport of nucleosides such as inosine, adenosine, uridine, thymidine, cytidine and guanosine (PubMed:11085929). Also able to transport purine nucleobases (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil) (By similarity). Involved in nucleoside transport at basolateral membrane of kidney cells, allowing liver absorption of nucleoside metabolites (By similarity). Mediates apical nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis-barrier (By similarity). Mediates both the influx and efflux of hypoxanthine in skeletal muscle microvascular endothelial cells to control the amount of intracellular hypoxanthine available for xanthine oxidase-mediated ROS production (By similarity).|||By platelet derived growth factor (PDGF) and fibroblast growth factor (FGF).|||Nucleus membrane|||Transport activity is insensitive to nanomolar concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR). http://togogenome.org/gene/10090:Trib2 ^@ http://purl.uniprot.org/uniprot/Q8K4K3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.|||Cytoplasm|||Interacts with MAPK kinases and regulates activation of MAP kinases. Does not display kinase activity (By similarity).|||The protein kinase domain is predicted to be catalytically inactive.|||cytoskeleton http://togogenome.org/gene/10090:Gpld1 ^@ http://purl.uniprot.org/uniprot/Q8R432|||http://purl.uniprot.org/uniprot/Q8VCU2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the GPLD1 family.|||Secreted http://togogenome.org/gene/10090:Idh1 ^@ http://purl.uniprot.org/uniprot/O88844 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-374 dramatically reduces catalytic activity.|||Belongs to the isocitrate and isopropylmalate dehydrogenases family.|||Binds 1 Mg(2+) or Mn(2+) ion per subunit.|||Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase (PubMed:12031902, PubMed:29923039). Plays a critical role in the generation of NADPH, an important cofactor in many biosynthesis pathways (PubMed:12031902). May act as a corneal epithelial crystallin and may be involved in maintaining corneal epithelial transparency (By similarity).|||Highly expressed in the liver followed by kidney, lower expression in spleen, brain and lung.|||Homodimer.|||Irreversibly inhibited by Cd(2+) concentrations above 50 uM.|||cytosol http://togogenome.org/gene/10090:Prss28 ^@ http://purl.uniprot.org/uniprot/Q924N9 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||By progesterone.|||Expressed in embryos throughout the preimplantation period, during blastocyst hatching and embryo outgrowth. Found in uterus especially in glandular epithelium.|||Highly expressed from 6.5 dpc in embryo plus deciduum. Faintly detectable at 11.5 dpc and 13.5 dpc in placenta. Not detected at 8.5 dpc, 11.5 dpc and 13.5 dpc in embryo proper. Expressed at 4.0 dpc in uterus.|||Homooligomer, heterodimer and heterotetramer. Able to form homo- and hetero- tetrameric structures. Heterotetramer is far more stable than the homotetramer.|||Inhibited by benzamidine, (4-amidino-phenyl)-methane-sulfonyl (APMSF), N-p-tosyl-L-lysine chloromethylketone (TLCK), gabexate, mesylate, BABIM and trypsin soybean inhibitor (TSI).|||Involved in embryo hatching and implantation.|||Secreted http://togogenome.org/gene/10090:Gatd1 ^@ http://purl.uniprot.org/uniprot/Q8BFQ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C56 family.|||Secreted http://togogenome.org/gene/10090:Eif4h ^@ http://purl.uniprot.org/uniprot/Q3TG58|||http://purl.uniprot.org/uniprot/Q564E5|||http://purl.uniprot.org/uniprot/Q9WUK2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at high levels in heart, liver and testis and at lower levels in brain, spleen, lung, skeletal muscle, kidney and embryonic tissues. Both isoforms are expressed at similar levels.|||Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA (By similarity).|||Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA.|||perinuclear region http://togogenome.org/gene/10090:Mppe1 ^@ http://purl.uniprot.org/uniprot/Q80XL7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallophosphoesterase superfamily. MPPE1 family.|||Binds 2 manganese ions per subunit.|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Interacts with GPI-anchor proteins. Interacts with TMED10 (By similarity).|||Metallophosphoesterase required for transport of GPI-anchor proteins from the endoplasmic reticulum to the Golgi. Acts in lipid remodeling steps of GPI-anchor maturation by mediating the removal of a side-chain ethanolamine-phosphate (EtNP) from the second Man (Man2) of the GPI intermediate, an essential step for efficient transport of GPI-anchor proteins (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Ptgds ^@ http://purl.uniprot.org/uniprot/O09114 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in the brain and CNS, where it is expressed in tissues of the blood-brain barrier and secreted into the cerebro-spinal fluid. In the male reproductive system, it is expressed in the testis, efferent ducts and epididymis, and is secreted into the seminal fluid. In the eye, it is expressed in the pigmented epithelium of the retina and the nonpigmented epithelium of the ciliary body, and secreted into the aqueous humor. Low levels detected in various tissue fluids such as serum, normal urine, ascitic fluid and tear fluid. Also found in a number of other organs including the ear, heart and lung.|||Belongs to the calycin superfamily. Lipocalin family.|||By IL-1 beta and thyroid hormone. Probably induced by dexamethasone, dihydrotestosterone, progesterone, retinoic acid and retinal. Repressed by the Notch-Hes signaling pathway.|||Catalyzes the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation. Involved in a variety of CNS functions, such as sedation, NREM sleep and PGE2-induced allodynia, and may have an anti-apoptotic role in oligodendrocytes. Binds small non-substrate lipophilic molecules, including biliverdin, bilirubin, retinal, retinoic acid and thyroid hormone, and may act as a scavenger for harmful hydrophobic molecules and as a secretory retinoid and thyroid hormone transporter. Possibly involved in development and maintenance of the blood-brain, blood-retina, blood-aqueous humor and blood-testis barrier. It is likely to play important roles in both maturation and maintenance of the central nervous system and male reproductive system (PubMed:10781097, PubMed:11751991, PubMed:12077186, PubMed:17715133, PubMed:19546224, PubMed:19833210, PubMed:8922532, PubMed:9892701). Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by immature mast cells and acts on nearby fibroblasts upstream to PTDGS to synthesize PGD2, which in turn promotes mast cell maturation and degranulation via PTGDR (PubMed:23624557).|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Golgi apparatus|||Initially detected at 14.5 dpc in the mesenchymal cells of the brain. Later in development, observed in the choroid plexus and within single cells in the brain.|||Monomer.|||Mutant mice show decreased susceptibility to passive cutaneous anaphylaxis associated with decreased mast cell degranulation.|||Nucleus membrane|||Rough endoplasmic reticulum|||Secreted|||perinuclear region http://togogenome.org/gene/10090:Hook2 ^@ http://purl.uniprot.org/uniprot/Q3TKK8|||http://purl.uniprot.org/uniprot/Q7TMK6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hook family.|||Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Contributes to the establishment and maintenance of centrosome function. May function in the positioning or formation of aggresomes, which are pericentriolar accumulations of misfolded proteins, proteasomes and chaperones. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.|||Cytoplasm|||Expressed in brain, cerebellum, kidney, liver and heart, with highest levels in heart and kidney (at protein level).|||Self-associates (By similarity). Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3 (By similarity). May interact directly with AKTIP/FTS, HOOK1 and HOOK3 (By similarity). Associates with several subunits of the homotypic vesicular sorting complex (the HOPS complex) including VPS16 and VPS41; these interactions may be indirect (By similarity). Interacts with CNTRL (By similarity). Interacts with microtubules (By similarity). Interacts with ZC3H14 (By similarity). Interacts with LRGUK (via guanylate kinase-like domain) (PubMed:25781171, PubMed:28003339). Interacts with CCDC181 (PubMed:28283191). Interacts with AP4M1; the interaction is direct, mediates the interaction between FTS-Hook-FHIP (FHF) complex and AP-4 and the perinuclear distribution of AP-4 (By similarity).|||centrosome|||cytoskeleton|||trans-Golgi network http://togogenome.org/gene/10090:Pla2g4a ^@ http://purl.uniprot.org/uniprot/P47713|||http://purl.uniprot.org/uniprot/Q3UMQ1|||http://purl.uniprot.org/uniprot/Q9DBX5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by cytosolic calcium, which is necessary for binding to membrane lipids (PubMed:1904318). Activated by phosphorylation in response to mitogenic stimuli (PubMed:10978317). Stimulated by agonists such as ATP and thrombin (PubMed:10978317).|||Cytoplasm|||Expressed in various organs including uterus, kidney, spleen, liver, heart, lung and brain (at protein level).|||Golgi apparatus membrane|||Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:1904318, PubMed:9403692, PubMed:9403693). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (PubMed:9403692, PubMed:9403693). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway. In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific. Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides. Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (By similarity).|||Interacts with KAT5.|||Mutant female mice have reduced fertility and produce small litters that most commonly result in dead pups. The pregnancy failure is likely due to a deficient implantation and parturition (PubMed:9403693, PubMed:9403692). In an inflammatory setting, mutant mice are protected against various pathological changes (PubMed:9403692, PubMed:9403693, PubMed:11984592, PubMed:16172261). In a bleomycin-induced model of pulmonary fibrosis, mutant mice show an attenuated lung inflammation characterized by impaired induction of eicosanoid synthesis and impaired inflammatory leukocyte migration to the lung (PubMed:11984592). Mutant mice are resistant to experimental autoimmune encephalomyelitis due to impaired T helper 1 type immune response (PubMed:16172261). They are also partially protected against cerebral ischaemia and reperfusion (PubMed:9403693). In a systemic anaphylaxis model, mutant mice show reduced allergen-induced bronchial hyperactivity (PubMed:9403692).|||Nucleus envelope|||Phosphorylated at both Ser-505 and Ser-726 in response to mitogenic stimuli.|||The N-terminal C2 domain associates with lipid membranes upon calcium binding.|||The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic calcium. In the presence of phosphoinositides, regulates phospholipase A2 and lysophospholipase activities in a calcium-independent way. http://togogenome.org/gene/10090:Exoc5 ^@ http://purl.uniprot.org/uniprot/Q3TPX4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC10 family.|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Cytoplasm|||Midbody|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8 (By similarity). Interacts with EXOC3L1 (PubMed:18480549). http://togogenome.org/gene/10090:Plk4 ^@ http://purl.uniprot.org/uniprot/Q64702 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.|||Cleavage furrow|||Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains can simultaneously bind to both TENT5C and CEP192.|||Death during embryogenesis. Embryos arrest after gastrulation at E7.5, with a marked increase in mitotic and apoptotic cells. Heterozygous mice are viable but show increased liver and lung cancers in elderly mice. Defects in heterozygous mice are associated with progressive cell cycle delays, increased spindle irregularities and accelerated hepatocellular carcinogenesis, probably due to increased centrosomal amplification, multipolar spindle formation and aneuploidy. The incidence of spontaneous.|||Homodimer (PubMed:12352953). Interacts with CEP152 (via N-terminus) (By similarity). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles (By similarity). Interacts with CEP131 (By similarity). Interacts simultaneously with TENT5C and CEP192. Interacts with TENT5C; this interaction leads to the TENT5C recruitment in the centrosome (By similarity).|||Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Phosphorylates CDC25C and CHEK2. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (By similarity). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (By similarity).|||Tyrosine-phosphorylated by TEC.|||Ubiquitinated; leading to its degradation by the proteasome.|||centriole|||centrosome|||expressed in tissues associated with mitotic and meiotic cell division. Highly expressed in testis.|||nucleolus http://togogenome.org/gene/10090:Cx3cr1 ^@ http://purl.uniprot.org/uniprot/Q543X3|||http://purl.uniprot.org/uniprot/Q9Z0D9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Found in a ternary complex with CX3CL1 and ITGAV:ITGB3 or ITGA4:ITGB1.|||Membrane|||No visible phenotype in normal conditions; mice develop normally and are fertile (PubMed:10805752). Mice lacking both Cx3cr1 and Apoe show decreased atherogenesis (PubMed:12569158). In experimental autoimmune encephalomyelitis (EAE) model mice, recruitment of natural killer (NK) cells in the inflamed central nervous system (CNS) is impaired, leading to increased EAE-related mortality, nonremitting spastic paraplegia and hemorrhagic inflammatory lesions (PubMed:16675847). Mice show an increased microglial inflammatory response and neuronal death in several models of CNS insult (PubMed:16732273). Mice display reduced airway inflammation in lung after allergen sensitization (PubMed:21037587). Mice display a transient decrease in microglia density, leading to synaptic deficits characterized by an excess of weak excitatory synapses: defects are caused by a failure to eliminate immature synaptic connections during the second and third postnatal weeks (PubMed:21778362). Deficient synaptic pruning is associated with weak synaptic transmission, decreased functional brain connectivity, deficits in social interaction and increased repetitive-behavior phenotypes (PubMed:24487234). Defects of lamina propria dendritic cells are observed, leading to impair the sampling of bacteria from the intestinal lumen and affect their ability to take up invasive pathogens (PubMed:15653504). Mice are more susceptible to severe colitis that is rescued by antifungal treatment and display changes in gut fungal communities (PubMed:29326275).|||Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chemotaxis (PubMed:9918795, PubMed:10187784). CX3CR1-CX3CL1 signaling mediates cell migratory functions (PubMed:11544273, PubMed:12871640, PubMed:16675847, PubMed:18322241). Responsible for the recruitment of natural killer (NK) cells to inflamed tissues (PubMed:11544273, PubMed:16675847). Acts as a regulator of inflammation process leading to atherogenesis by mediating macrophage and monocyte recruitment to inflamed atherosclerotic plaques, promoting cell survival (PubMed:12569158, PubMed:18971423). Involved in airway inflammation by promoting interleukin 2-producing T helper (Th2) cell survival in inflamed lung (PubMed:21037587). Involved in the migration of circulating monocytes to non-inflamed tissues, where they differentiate into macrophages and dendritic cells (PubMed:12871640). Acts as a negative regulator of angiogenesis, probably by promoting macrophage chemotaxis (PubMed:18322241). Plays a key role in brain microglia by regulating inflammatory response in the central nervous system (CNS) and regulating synapse maturation (PubMed:16732273, PubMed:21778362, PubMed:24487234). Required to restrain the microglial inflammatory response in the CNS and the resulting parenchymal damage in response to pathological stimuli (PubMed:16732273). Involved in brain development by participating in synaptic pruning, a natural process during which brain microglia eliminates extra synapses during postnatal development (PubMed:21778362). Synaptic pruning by microglia is required to promote the maturation of circuit connectivity during brain development (PubMed:24487234). Acts as an important regulator of the gut microbiota by controlling immunity to intestinal bacteria and fungi (PubMed:15653504, PubMed:29326275). Expressed in lamina propria dendritic cells in the small intestine, which form transepithelial dendrites capable of taking up bacteria in order to provide defense against pathogenic bacteria (PubMed:15653504). Required to initiate innate and adaptive immune responses against dissemination of commensal fungi (mycobiota) component of the gut: expressed in mononuclear phagocytes (MNPs) and acts by promoting induction of antifungal IgG antibodies response to confer protection against disseminated C.albicans or C.auris infection (PubMed:29326275, PubMed:33548172). Also acts as a receptor for C-C motif chemokine CCL26, inducing cell chemotaxis (By similarity).|||Specifically expressed in subsets of leukocytes: expressed in monocytes, subsets of T-cells and natural killer (NK) cells in the circulation, dendritic cells, as well as in microglia in the central nervous system (CNS) (PubMed:10805752, PubMed:12871640, PubMed:16732273). Expression level subdivides blood monocytes into two major functional subsets; CD14(+)CD16(-)-CX3CR1(low) inflammatory monocytes and CD14(low)CD16(+)CX3CR1(high) homeostatic monocytes (PubMed:12871640). Expressed in myeloid-derived mucosal dendritic cells, which populate the entire lamina propria of the small intestine (PubMed:15653504).|||This protein is not N-glycosylated which is unusual for G-protein-coupled receptors. http://togogenome.org/gene/10090:Prmt5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J049|||http://purl.uniprot.org/uniprot/Q8CIG8 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment.|||Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:15485929, PubMed:19584108, PubMed:19858291, PubMed:21917714, PubMed:23133559, PubMed:28263986). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Methylates SUPT5H and may regulate its transcriptional elongation properties (By similarity). May methylate the N-terminal region of MBD2 (By similarity). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation (By similarity). Methylates histone H2A and H4 'Arg-3' during germ cell development (PubMed:16699504). Methylates histone H3 'Arg-8', which may repress transcription (PubMed:15485929). Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (PubMed:19584108). Methylates RPS10 (By similarity). Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (By similarity). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (PubMed:23133559). Methylates GM130/GOLGA2, regulating Golgi ribbon formation. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression. Symmetrically methylates NCL. Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (By similarity). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (PubMed:28263986).|||Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).|||Belongs to the class I-like SAM-binding methyltransferase superfamily.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.|||Cytoplasm|||Forms, at least, homodimers and homotetramers. Component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A. Found in a complex composed of PRMT5, WDR77 and RIOK1. RIOK1 and CLNS1A associate with PRMT5 in a mutually exclusive fashion, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively (By similarity). Interacts with PRDM1 (PubMed:16699504). Identified in a complex composed of methylosome and PRMT1 and ERH. Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2 (By similarity). Found in a complex with COPRS, RUNX1 and CBFB (PubMed:22193545). Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1 (PubMed:19858291, PubMed:22872859). Interacts with EPB41L3; this modulates methylation of target proteins. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1. Interacts with LSM11, PRMT7 and SNRPD3. Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln. Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10. Interacts with WDR77 (By similarity). Interacts with IWS1. Interacts with CRY1 (PubMed:23133559). Interacts with POLR2A. Interacts with SMN1/SMN2. Interacts with LYAR; this interaction is direct. Interacts with TTC5/STRAP; this interaction is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53. Interacts with p53/TP53 in response to DNA damage; the interaction is TTC5/STRAP dependent. Interacts with FAM47E; the interaction is direct, promotes PRMT5 localization to chromatin, and does not disrupt its association with WDR77 or STUB1 (By similarity). Interacts with TDRD6 (PubMed:28263986). Interacts with STUB1 (By similarity). Interacts with MBD2 (By similarity). Does not interact with MBD3 (By similarity).|||Golgi apparatus|||Nucleus http://togogenome.org/gene/10090:Hes3 ^@ http://purl.uniprot.org/uniprot/Q61657 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).|||Nucleus|||The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.|||Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.|||Transcriptional repressor of genes that require a bHLH protein for their transcription. http://togogenome.org/gene/10090:Dync2i2 ^@ http://purl.uniprot.org/uniprot/Q5U4F6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Inhibits the MAP3K7-induced NF-kappa-B activation pathway. Inhibits MAP3K7 phosphorylation at 'Thr-184' and 'Thr-187' upon Il-1 beta stimulation.|||Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system. DYNC2I2 plays a major role in retrograde ciliary protein trafficking and in ciliogenesis (PubMed:28379358). Required also to maintain a functional transition zone (By similarity).|||Belongs to the dynein light intermediate chain family.|||Cytoplasm|||Expressed in brain, thymus, heart, lung, liver, spleen, kidney, testis and intestine.|||The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the cytoplasmic dynein complex 2, but a subset of the light chains are also shared by dynein-1 and dynein-2 complexes. Interacts with DYNC2I1; their C-terminal domains each bind a copy of the heavy chain, and their extended N-terminal regions are held together by an array of light chain dimers. Interacts with DYNLL2; this interaction is essential for dynein-2-mediated retrograde trafficking of ciliary proteins. Interacts with DYNLRB1; this interaction is essential for dynein-2-mediated retrograde trafficking of ciliary proteins. Interacts (via the WD domains) with MAP3K7 and TAB3. Interacts (via WD domains) with TAB2 (via C-terminus). Interacts (via WD domains) with TRAF6 (via TRAF-type domains).|||The majority of deficient mice die in midgestation from 10.5 dpc to 12.5 dpc. The mutant embryos exhibit open brain, spinal bifida, microphthalmia, and polydactyly. Inactivation of the protein results also in short and stumpy cilia with an abnormal accumulation of ciliary proteins and defects in Sonic hedgehog signaling.|||centrosome|||cilium|||cilium axoneme|||cilium basal body|||filopodium http://togogenome.org/gene/10090:Gdpd5 ^@ http://purl.uniprot.org/uniprot/A0A1L1STK0|||http://purl.uniprot.org/uniprot/Q640M6 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Detected in brain, lung, heart, kidney and testis.|||Endomembrane system|||Glycerophosphodiester phosphodiesterase that promotes neurite formation and drives spinal motor neuron differentiation (PubMed:17275818, PubMed:18667693). Mediates the cleavage of glycosylphosphatidylinositol (GPI) anchor of target proteins: removes the GPI-anchor of RECK, leading to release RECK from the plasma membrane (By similarity). May contribute to the osmotic regulation of cellular glycerophosphocholine (PubMed:18667693).|||Inhibited by high level of NaCl or urea.|||Interacts with PRDX1; forms a mixed-disulfide with PRDX1, leading to disrupt intramolecular disulfide bond between Cys-25 and Cys-571.|||Intramolecular disulfide bond between Cys-25 and Cys-571 is reduced by PRDX1.|||Up-regulated during neuronal differentiation by retinoic acid. Down regulated by high NaCl or urea (PubMed:18667693).|||growth cone|||perinuclear region http://togogenome.org/gene/10090:Zscan29 ^@ http://purl.uniprot.org/uniprot/A2ARU5 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Tph1 ^@ http://purl.uniprot.org/uniprot/P17532|||http://purl.uniprot.org/uniprot/Q3TZH2|||http://purl.uniprot.org/uniprot/Q3UK52|||http://purl.uniprot.org/uniprot/Q9JHZ8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.|||Homotetramer.|||Mice display impaired hemostasis, resulting in a reduced risk of thrombosis and thromboembolism, although the ultrastructure of the platelets is not affected (PubMed:14697203). Blood platelet counts are normal (PubMed:14697203). Defects are caused by inability to inability to mediate protein serotonylation of small GTPases during activation and aggregation of platelets (PubMed:14697203).|||Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-determining step of serotonin biosynthesis.|||Phosphorylated; triggering degradation by the proteasome.|||Ubiquitinated, leading to its degradation by the proteasome. Ubiquitinated is triggered by phosphorylation. http://togogenome.org/gene/10090:Faap24 ^@ http://purl.uniprot.org/uniprot/Q8BHL6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9, FANCM and FAAP24. Interacts with FANCM (By similarity).|||Nucleus|||Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA (By similarity).|||The C-terminal region is distantly related to RuvA domain 2, a DNA-binding domain. http://togogenome.org/gene/10090:Sp9 ^@ http://purl.uniprot.org/uniprot/Q64HY3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Detected in the apical ectodermal ridge (AER) during limb development as well as in the distal region of the ectoderm.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP9, the motif is inactive.|||Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos. http://togogenome.org/gene/10090:Ids ^@ http://purl.uniprot.org/uniprot/Q08890 ^@ Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||By glucose, in a dose dependent manner.|||Found to be expressed in alpha and beta pancreatic cells.|||Lysosomal enzyme involved in the degradation pathway of dermatan sulfate and heparan sulfate.|||Lysosome|||Monomer. The 58-kDa mature form is composed of two chains resulting from proteolitic processing, the 42-kDa chain and the 14-kDa chain that remain stably associated and form the 58-kDa intermediate form which is enzymatically active.|||Synthesized as a 75-kDa precursor form in the endoplasmic reticulum (ER), and then processed by proteolytic cleavage through various intermediates to yield a 55-kDa mature form, with the release of an 18 kDa polypeptide.|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:St14 ^@ http://purl.uniprot.org/uniprot/P56677|||http://purl.uniprot.org/uniprot/Q543E3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site (By similarity). Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing (By similarity). Proteolytically cleaves and therefore activates TMPRSS13 (By similarity).|||Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site.|||Highly expressed in intestine, kidney, lung, and thymus. Not expressed in skeletal muscle, liver, heart, testis and brain.|||Interacts with CDCP1. May interact with TMEFF1 (By similarity).|||Interacts with CDCP1. May interact with TMEFF1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Osm ^@ http://purl.uniprot.org/uniprot/P53347 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LIF/OSM family.|||Growth regulator. Inhibits the proliferation of a number of tumor cell lines. It regulates cytokine production, including IL-6, G-CSF and GM-CSF from endothelial cells (By similarity). Uses only type II OSM receptor (heterodimers composed of OSMR and IL6ST). Involved in the maturation of fetal hepatocytes, thereby promoting liver development and regeneration (By similarity).|||Propeptide processing is not important for receptor binding activity but may be important growth-inhibitory activity.|||Secreted http://togogenome.org/gene/10090:Ppp1r12a ^@ http://purl.uniprot.org/uniprot/Q9DBR7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in striated and vascular smooth muscle, specificcally in type 2a fibers (at protein level). Expression levels are 20-30% higher in developed males than females (at protein level).|||Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.|||In neonates, expressed at low levels in striated and smooth muscles. As the animals mature sexually, expression increases 10-20-fold. Pregnancy promotes a 2-3-fold increase in expression in striated, vascular and uterine muscle (at protein level). Expressed in the prosencephalic neural folds at 8.5 dpc. Expressed in the lower urinary tract, specifically in epitheliumof the bladder, urethra, and genital tubercle at 13.5 dpc (PubMed:31883643).|||Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity (By similarity).|||PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, and one or several targeting or regulatory subunits. PPP1R12A mediates binding to myosin. Interacts with ARHA and CIT (By similarity). Binds PPP1R12B, ROCK1 and IL16. Interacts directly with PRKG1. Non-covalent dimer of 2 dimers; PRKG1-PRKG1 and PPP1R12A-PPP1R12A. Interacts with SMTNL1 (By similarity). Interacts with PPP1CB; the interaction is direct. Interacts (when phosphorylated at Ser-445, Ser-472 and Ser-910) with 14-3-3. Interacts with ROCK1 and ROCK2. Interacts with isoform 1 and isoform 2 of ZIPK/DAPK3. Interacts with RAF1. Interacts with HIF1AN (By similarity). Interacts with NCKAP1L (By similarity).|||Phosphorylated by CIT (Rho-associated kinase) (By similarity). Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-694 (By similarity). Phosphorylated on upon DNA damage, probably by ATM or ATR. In vitro, phosphorylation of Ser-693 by PKA and PKG appears to prevent phosphorylation of the inhibitory site Thr-694, probably mediated by PRKG1. Phosphorylation at Ser-445, Ser-472 and Ser-909 by NUAK1 promotes interaction with 14-3-3, leading to inhibit interaction with myosin light chain MLC2, preventing dephosphorylation of MLC2. May be phosphorylated at Thr-694 by DMPK; may inhibit the myosin phosphatase activity (By similarity). Phosphorylated at Ser-473 by CDK1 during mitosis, creating docking sites for the POLO box domains of PLK1. Subsequently, PLK1 binds and phosphorylates PPP1R12A (By similarity).|||The KVKF motif mediates interaction with PPP1CB.|||stress fiber http://togogenome.org/gene/10090:Leprotl1 ^@ http://purl.uniprot.org/uniprot/Q9CQ74 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OB-RGRP/VPS55 family.|||Interacts with RAB13.|||Membrane|||Negatively regulates growth hormone (GH) receptor cell surface expression in liver. May play a role in liver resistance to GH during periods of reduced nutrient availability.|||Up-regulated in the liver of fasting animals. http://togogenome.org/gene/10090:Mrpl32 ^@ http://purl.uniprot.org/uniprot/Q9DCI9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL32 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Patl1 ^@ http://purl.uniprot.org/uniprot/Q3TC46 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PAT1 family.|||Interacts (via region A) with DDX6/RCK. Interacts (via region H and region C) with LSM1 and LSM4. Interacts (via region N) with DCP1A, DCP2, EDC3, EDC4 and XRN1. Interacts with the CCR4-NOT complex. Interacts with the Lsm-containing SMN-Sm protein complex. Interacts with EIF4ENIF1/4E-T.|||Nucleus|||Nucleus speckle|||P-body|||PML body|||RNA-binding protein involved in deadenylation-dependent decapping of mRNAs, leading to the degradation of mRNAs. Acts as a scaffold protein that connects deadenylation and decapping machinery. Required for cytoplasmic mRNA processing body (P-body) assembly.|||The region C, also named Pat-C, is required for RNA-binding and mediates the binding with the Lsm-containing SMN-Sm protein complex and the decapping machinery. It folds into an alpha-alpha superhelix, exposing conserved and basic residues on one side of the domain. http://togogenome.org/gene/10090:Dtd1 ^@ http://purl.uniprot.org/uniprot/Q9DD18 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A Gly-cisPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of L-amino acids.|||ATPase involved in DNA replication, may facilitate loading of CDC45 onto pre-replication complexes.|||An aminoacyl-tRNA editing enzyme that deacylates mischarged D-aminoacyl-tRNAs. Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS. Acts via tRNA-based rather than protein-based catalysis; rejects L-amino acids rather than detecting D-amino acids in the active site. By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality.|||Belongs to the DTD family.|||Cytoplasm|||Homodimer. Interacts with CDC45 and TOPBP1 (By similarity).|||Nucleus|||Preferentially phosphorylated in cells arrested early in S phase. Phosphorylation in the C-terminus weakens the interaction with CDC45 (By similarity). http://togogenome.org/gene/10090:Retreg1 ^@ http://purl.uniprot.org/uniprot/Q8VE91 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RETREG family.|||Endoplasmic reticulum (ER)-anchored autophagy regulator which mediates ER delivery into lysosomes through sequestration into autophagosomes (PubMed:26040720, PubMed:34338405). Promotes membrane remodeling and ER scission via its membrane bending capacity and targets the fragments into autophagosomes via interaction with ATG8 family proteins (PubMed:26040720, PubMed:34338405). Active under basal conditions (By similarity). Required for collagen quality control in a LIR motif-dependent manner (PubMed:34338405). Required for long-term survival of nociceptive and autonomic ganglion neurons (PubMed:19838196, PubMed:26040720).|||Endoplasmic reticulum membrane|||Homooligomer; oligomerization is enhanced following endoplasmic reticulum stress and is mediated by the reticulon homology domain (By similarity). Interacts with ATG8 family modifier proteins MAP1LC3A, MAP1LC3B, GABARAPL1 and GABARAPL2 (PubMed:34338405). Also interacts with ATG8 family modifier protein GABARAP (By similarity).|||Leads to an expanded endoplasmic reticulum.|||Phosphorylation at Thr-134 by CAMK2B enhances oligomerization and membrane scission and reticulophagy activity.|||Predicted by similarity to human,.|||The LIR motif interacts with ATG8 family proteins and is necessary to target the ER fragments to autophagosomes for lysosomal degradation.|||The reticulon homology domain provides capacity to bend the membrane and promotes ER scission (PubMed:26040720). It is required for homooligomerization (By similarity). This domain does not show relevant similarities with reticulon domains, preventing any domain predictions within the protein sequence.|||Widely expressed with highest levels in brain, lung, liver, muscle and spleen (at protein level) (PubMed:34338405). Detected specifically in organelle-like intracellular structures of the small and large neurons of dorsal root ganglia (DRG) (at protein level) (PubMed:19838196, PubMed:31930741). Predominantly expressed in sensory and autonomic ganglia at embryonic day 14.5 (PubMed:19838196).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Angpt4 ^@ http://purl.uniprot.org/uniprot/Q9WVH6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to TEK/TIE2, modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2. Promotes endothelial cell survival, migration and angiogenesis.|||Homodimer; disulfide-linked. Interacts with TEK/TIE2.|||Secreted|||Widely expressed. http://togogenome.org/gene/10090:Apc2 ^@ http://purl.uniprot.org/uniprot/G5E832 ^@ Similarity ^@ Belongs to the adenomatous polyposis coli (APC) family. http://togogenome.org/gene/10090:Hebp1 ^@ http://purl.uniprot.org/uniprot/A0A140T8J4|||http://purl.uniprot.org/uniprot/Q9R257 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HEBP family.|||Cytoplasm|||Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure.|||May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities.|||Monomer.|||Ubiquitously expressed. Extremely abundant in liver. http://togogenome.org/gene/10090:Saa2 ^@ http://purl.uniprot.org/uniprot/P05367 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apolipoprotein of the HDL complex.|||Belongs to the SAA family.|||Expressed by the liver; secreted in plasma.|||Major acute phase reactant.|||Secreted http://togogenome.org/gene/10090:Optn ^@ http://purl.uniprot.org/uniprot/Q8K3K8 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic vesicle|||Expressed from 7-day-old embryos.|||Golgi apparatus|||In eye, it is expressed in anterior segment, retina, and optic nerve blood vessels (at protein level). Highly expressed in adult liver, heart and testis.|||OPTN E59K transgenic mice exhibit profound gliosis in the retina.|||OPTN-deficient cells display reduced TBK1 activation, IRF3 phosphorylation, and expression of type I IFNs in response to TLR3 and TLR4 stimulation, indicating a role for OPTN in the innate immune response.|||Phosphorylated by TBK1, leading to restrict bacterial proliferation in case of infection.|||Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8. Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation. Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation. In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment. Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52.|||Recycling endosome|||Self-associates (By similarity). Interacts with HD, GTF3A, TRAF3, TBK1 and MYO6. Interacts (via UBAN) with ubiquitinated TFRC. Interacts with active GTP-bound Rab8 (RAB8A and/or RAB8B). Interacts with TBC1D17. Binds to linear ubiquitin chains. Interacts with LC3 family members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN phosphorylation increases the association (at least with MAP1LC3B). Interacts with RAB12; the interaction may be indirect. Interacts with TBK1; this interaction leads to the Golgi localization of TBK1 and its subsequent activation. Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction does not lead to palmitoylation of OPTN (By similarity). Interacts with CYLD (By similarity). Interacts with TOM1; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and OPTN (By similarity).|||The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.|||Ubiquitin-binding motif (UBAN) is essential for its inhibitory function, subcellular localization and interaction with TBK1.|||autophagosome|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Jrkl ^@ http://purl.uniprot.org/uniprot/B2RRL2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tigger transposable element derived protein family.|||Nucleus http://togogenome.org/gene/10090:Mapre3 ^@ http://purl.uniprot.org/uniprot/D3Z6G3|||http://purl.uniprot.org/uniprot/Q2UZW7|||http://purl.uniprot.org/uniprot/Q6PER3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAPRE family.|||Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1.|||Homodimer (By similarity). Heterodimer with MAPRE1 (By similarity). Binds monomeric and polymerized GTP-bound tubulin. Interacts with DCTN1 and SRCIN1 (By similarity). Binds to the C-terminal domain of APC (By similarity). Interacts (via C-terminus) with CLIP1 (By similarity). Interacts with SLAIN2 (By similarity). Interacts with SLAIN1 (PubMed:21646404). Interacts with APC2 (PubMed:17310996). Interacts with AKAP9 (By similarity). Interacts with PDE4DIP isoform 2/MMG8/SMYLE; this interaction is required for its recruitment to the Golgi apparatus (By similarity).|||Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Eif1ad8 ^@ http://purl.uniprot.org/uniprot/Q3UTA4 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Gm4836 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Lrrc39 ^@ http://purl.uniprot.org/uniprot/Q8BGI7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress. May regulate expression of other M-band proteins via an SRF-dependent pathway. Important for normal contractile function in heart.|||Expressed in heart and skeletal muscle.|||Interacts with MYH7 (via C-terminus).|||M line http://togogenome.org/gene/10090:Faah ^@ http://purl.uniprot.org/uniprot/O08914 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the amidase family.|||Catalyzes the hydrolysis of endogenous amidated lipids like the endocannabinoid anandamide (N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine), as well as other fatty amides such as the taurine-conjugated fatty acids (a structural class of central nervous system (CNS) metabolites), to their corresponding fatty acids, thereby regulating the signaling functions of these molecules (PubMed:15533037, PubMed:32271712). FAAH cooperates with PM20D1 in the hydrolysis of amino acid-conjugated fatty acids such as N-fatty acyl glycine and N-fatty acyl-L-serine, thereby acting as a physiological regulator of specific subsets of intracellular, but not of extracellular, N-fatty acyl amino acids (PubMed:32271712). It can also catalyze the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol) (By similarity).|||Endoplasmic reticulum membrane|||Genetic ablation of FAAH bidirectionally dysregulates a subset of intracellular, but not circulating, N-fatty acyl amino acids.|||Golgi apparatus membrane|||Homodimer.|||Inhibited the trifluoromethyl compound PF-3845. http://togogenome.org/gene/10090:Nectin2 ^@ http://purl.uniprot.org/uniprot/P32507 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nectin family.|||Brain, spinal cord, spleen, kidney, heart and liver.|||Can form trans-heterodimers with NECTIN3 (PubMed:10744716, PubMed:22902367). Interacts with CD226 or with PVRIG; these interactions are competitive and have a differential functional outcome on T-cell activation, either positive or negative, respectively. Binds with low affinity to TIGIT (By similarity).|||Cell membrane|||Modulator of T-cell signaling. Can be either a costimulator of T-cell function, or a coinhibitor, depending on the receptor it binds to. Upon binding to CD226, stimulates T-cell proliferation and cytokine production, including that of IL2, IL5, IL10, IL13, and IFNG. Upon interaction with PVRIG, inhibits T-cell proliferation. These interactions are competitive. Probable cell adhesion protein. http://togogenome.org/gene/10090:Cdk2 ^@ http://purl.uniprot.org/uniprot/P97377|||http://purl.uniprot.org/uniprot/Q3U6X7|||http://purl.uniprot.org/uniprot/Q3UGB9 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Binds 2 Mg(2+) ions.|||Cajal body|||Cytoplasm|||Endosome|||Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1 (PubMed:11585773). Interacts with UHRF2. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo proteins SPDYA and SPDYC. Interaction with SPDYA promotes kinase activation via a conformation change that alleviates obstruction of the substrate-binding cleft by the T-loop. Found in a complex with both SPDYA and CDKN1B/KIP1. Binds to RB1 and CDK7. Binding to CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Associated with PTPN6 and beta-catenin/CTNNB1. Interacts with CACUL1. May interact with CEP63. Interacts with ANKRD17 (By similarity). Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Forms a ternary complex with CCNA2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements. Interacts with cyclins A, B1, B3, D, or E. Interacts with CDK2AP2 (By similarity).|||Nitrosylated after treatment with nitric oxide (DETA-NO).|||Phosphorylated at Thr-160 by CDK7 in a CAK complex. Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A.|||Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it. Stimulated by MYC. Inactivated by CDKN1A (p21) (By similarity).|||Reduced body size and impaired neural progenitor cell proliferation. Sterility due to defective meiosis; no effect on mitotic cells. Premature translocation of CDK1 from the cytoplasm to the nucleus compensating CDK2 loss. Prolonged and impaired DNA repair activity upon DNA damage by gamma-irradiation.|||Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (PubMed:23853094). Phosphorylates CDK2AP2 (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (By similarity).|||centrosome http://togogenome.org/gene/10090:Chd9 ^@ http://purl.uniprot.org/uniprot/Q8BYH8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional coactivator for PPARA and possibly other nuclear receptors. Proposed to be a ATP-dependent chromatin remodeling protein. Has DNA-dependent ATPase activity and binds to A/T-rich DNA (By similarity). Associates with A/T-rich regulatory regions in promoters of genes that participate in the differentiation of progenitors during osteogenesis.|||Belongs to the SNF2/RAD54 helicase family.|||Cytoplasm|||Expressed from embryonic day 16.5 dpc in mesenchymal cartilage surrounding bone cartilage and newly formed bone trabecular spicules. Detected in bone sections of 4-day-old newborn and 3-week-old mice.|||Expressed in osteoprogenitor cells during development and in mature bone (at protein level).|||Interacts with PPARA. Probably interacts with ESR1 and NR1I3 (By similarity).|||Nucleus|||Phosphorylated on serine and tyrosine residues. http://togogenome.org/gene/10090:Cyp2f2 ^@ http://purl.uniprot.org/uniprot/P33267 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Club cells in lung and liver.|||Endoplasmic reticulum membrane|||Involved in the regio- and stereoselective transformation of naphthalene to trans-1R-hydroxy-2R-glutathionyl-1,2-dihydronaphthalene in the presence of glutathione and glutathione S-transferases. It specifically catalyzes the production of a very reactive and potentially toxic intermediate, the 2R,2S arene oxide, that is associated with necrosis of the unciliated bronchiolar epithelial cells or club cells in lung.|||Microsome membrane http://togogenome.org/gene/10090:COX2 ^@ http://purl.uniprot.org/uniprot/P00405|||http://purl.uniprot.org/uniprot/Q7JCZ1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 2 family.|||Binds a copper A center.|||Binds a dinuclear copper A center per subunit.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20. Interacts with COX16 (By similarity).|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20. Interacts with COX16.|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Slc17a1 ^@ http://purl.uniprot.org/uniprot/Q61983 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.|||Important for the resorption of phosphate by the kidney. May be involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. Plays a role in urate transport in the kidney.|||Interacts with PDZK1.|||Kidney. http://togogenome.org/gene/10090:Tamm41 ^@ http://purl.uniprot.org/uniprot/G5E881 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TAM41 family.|||Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or10j3 ^@ http://purl.uniprot.org/uniprot/E9PWV2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mup17 ^@ http://purl.uniprot.org/uniprot/B5X0G2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Because of their involvement in the coordination of social behavior, Mup proteins are thought to exhibit variable expression depending upon gender, age and status of the studied individuals. Expression may also be strain-specific: in strains C57BL/6J and 129S7, transcriptional support is lacking for Mup17.|||Belongs to the calycin superfamily. Lipocalin family.|||Major urinary proteins (Mups) bind pheromones, thus stabilize them and allow slow release into the air from urine marks. May protect pheromones from oxidation. May also act as pheromones themselves. In this context, they play a role in the regulation of social behaviors, such as aggression, mating, pup-suckling, territory establishment and dominance (By similarity).|||Mups are encoded by multiple paralogous genes which are very similar to each other, making accurate identification difficult. The recommended nomenclature used in this entry is based on that provided by the MGI database.|||Secreted http://togogenome.org/gene/10090:Or1m1 ^@ http://purl.uniprot.org/uniprot/Q8VFM9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in testis.|||Odorant receptor. http://togogenome.org/gene/10090:Or51q1 ^@ http://purl.uniprot.org/uniprot/K7N6B1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dhx40 ^@ http://purl.uniprot.org/uniprot/Q6PE54 ^@ Function|||Similarity ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Probable ATP-dependent RNA helicase. http://togogenome.org/gene/10090:Nt5c1a ^@ http://purl.uniprot.org/uniprot/A3KFX0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by ADP.|||Belongs to the 5'-nucleotidase type 3 family.|||Catalyzes the hydrolysis of ribonucleotide and deoxyribonucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside (By similarity). AMP is the major substrate but can also hydrolyze dCMP and IMP (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Cdh4 ^@ http://purl.uniprot.org/uniprot/P39038 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. May play an important role in retinal development.|||Cell membrane|||Distributed widely in mouse tissues with high levels present in brain, skeletal muscle and thymus.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Klrb1c ^@ http://purl.uniprot.org/uniprot/P27814 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in natural killer cells.|||Homodimer; disulfide-linked. Interacts with tyrosine kinase LCK.|||Membrane|||Plays a stimulatory role on natural killer (NK) cells cytotoxicity. Activation by cross-linking of the receptor induces Ca(2+) mobilization and interferon-gamma production.|||The anti-NK1.1 monoclonal antibody (PK136), recognizing Klrb1b and Klrb1c genes, is known to identify NK cells from B6 and SLJ mice, but not from BALB/c ones. A single mutation Thr-191 present in Klrb1b and Klrb1c genes of BALB/c mice may be responsible for lack of NK1.1 reactivity in these mice. Indeed, when Lys-217 of BALB/c mice Klrb1c is mutated to Glu-217 present in B6 and SLJ mice, it does not confer NK1.1 reactivity. http://togogenome.org/gene/10090:Kcnn2 ^@ http://purl.uniprot.org/uniprot/A0A1B0GT12|||http://purl.uniprot.org/uniprot/B4YDY0|||http://purl.uniprot.org/uniprot/P58390|||http://purl.uniprot.org/uniprot/Q8C7F3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel KCNN family. KCa2.2/KCNN2 subfamily.|||Expressed in atrial and ventricular myocytes with higher levels in atrial myocytes (at protein level). Highly expressed in brain, liver and colon with low levels in kidney and testis. In colon, detected in smooth muscle cells.|||Forms a voltage-independent potassium channel activated by intracellular calcium (PubMed:11557517, PubMed:13679367, PubMed:14657188). Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization.|||Heterooligomer. The complex is composed of 4 channel subunits each of which binds to a calmodulin subunit which regulates the channel activity through calcium-binding (By similarity). Interacts (via N-terminal domain) with MPP2 (PubMed:26880549).|||Inhibited by bee venom neurotoxin apamin (PubMed:11557517, PubMed:13679367, PubMed:14657188). Inhibited by UCL 1684 and tetraethylammonium (TEA) (By similarity).|||Membrane http://togogenome.org/gene/10090:Smyd4 ^@ http://purl.uniprot.org/uniprot/Q8BTK5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Cytoplasm|||Interacts (via MYND-type zinc finger) with HDAC1.|||Nucleus|||Plays a critical role in cardiac development (By similarity). Acts as a key epigenetic regulator of gene expression during cardiac development via its dual activities as a methyltransferase and negative regulator of HDAC1 (By similarity). http://togogenome.org/gene/10090:Champ1 ^@ http://purl.uniprot.org/uniprot/Q8K327 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Interacts with MAD2L2. Interacts with POGZ, CBX1, CBX3 and CBX5 (By similarity).|||Nucleus|||Phosphorylated by CDK1. Mitotic phosphorylation is required for the attachment of spindle microtubules to the kinetochore (By similarity).|||Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore (By similarity).|||kinetochore|||spindle http://togogenome.org/gene/10090:Palm ^@ http://purl.uniprot.org/uniprot/Q3TRX4|||http://purl.uniprot.org/uniprot/Q542N8|||http://purl.uniprot.org/uniprot/Q8CB16|||http://purl.uniprot.org/uniprot/Q9Z0P4 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apicolateral cell membrane|||Basolateral cell membrane|||Belongs to the paralemmin family.|||Cell membrane|||Expression is highest in brain, intermediate in adrenal gland and kidney, and much lower or undetectable in other tissues. Isoform 1 is the predominant isoform in most tissues except brain and kidney where isoform 2 predominates.|||In brain, expression is highest in neonates and declines to approximately 50% in adults. Isoform 2 is the predominant isoform in neonates with isoform 1 being barely detectable at this stage. Levels of isoform 1 increase with age, with the most pronounced increase between postnatal days 10 and 20.|||Interacts with dopamine receptor DRD3.|||Involved in plasma membrane dynamics and cell process formation. Isoform 1 and isoform 2 are necessary for axonal and dendritic filopodia induction, for dendritic spine maturation and synapse formation in a palmitoylation-dependent manner.|||Mutagenesis of Cys-333, Cys-335 and Cys-336 to Ser inhibit filopodia and spines induction and synapse maturation.|||axon|||dendrite|||dendritic spine|||filopodium membrane http://togogenome.org/gene/10090:Fah ^@ http://purl.uniprot.org/uniprot/P35505 ^@ Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the FAH family.|||Homodimer.|||Mainly in liver and kidney. http://togogenome.org/gene/10090:Mcts2 ^@ http://purl.uniprot.org/uniprot/Q9CQ21 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MCTS1 family.|||Cytoplasm|||Imprinted gene expressed from the paternal allele in blastocysts. http://togogenome.org/gene/10090:Shank2 ^@ http://purl.uniprot.org/uniprot/D3Z5K8|||http://purl.uniprot.org/uniprot/Q80Z38 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SHANK family.|||Cytoplasm|||Detected in brain (at protein level), where it is highly expressed in Purkinje cells.|||Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts with CTTN/cortactin SH3 domain, DLGAP1/GKAP and alpha-latrotoxin receptor 1. Interacts with DNM2, DBNL, GRID2, BAIAP2, SLC9A3, PLCB3 and CFTR. Interacts (via proline-rich region) with PDE4D. Interacts with ABI1 (via SH3 domain).|||Mutants are viable, but with reduced body weight and a lower survival rate compared to their wild-type littermates. They are extremely hiperactive and display profound autistic-like behavioral alterations including repetitive grooming as well as abnormalities in vocal and social behaviors. Mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced NMDA receptor-mediated excitatory currents at the physiological level. They also show a brain-region-specific up-regulation of ionotropic glutamate receptors and increased levels of SHANK3.|||Postsynaptic density|||Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction (By similarity).|||Synapse|||The PDZ domain is required for interaction with GRID2, PLCB3, SLC9A3 and CFTR.|||dendritic spine|||growth cone http://togogenome.org/gene/10090:Trem3 ^@ http://purl.uniprot.org/uniprot/Q9JKE1 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in macrophages and in T-cells.|||Forms a receptor signaling complex with TYROBP/DAP12 which mediates activation of macrophages as part of the innate immune response.|||Induced by lipopolysaccharide (LPS). Interferon gamma (IFNG) decreases expression.|||Interacts with TYROBP/DAP12. http://togogenome.org/gene/10090:Orc1 ^@ http://purl.uniprot.org/uniprot/Q3TPY7|||http://purl.uniprot.org/uniprot/Q3UR71|||http://purl.uniprot.org/uniprot/Q9Z1N2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORC1 family.|||Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase (By similarity). Interacts with CDC6 and KAT7/HBO1 (By similarity). Interacts with LRWD1 predominantly during the G1 phase and with less affinity during mitosis, when phosphorylated (By similarity).|||Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase. Interacts with CDC6 and KAT7/HBO1. Interacts with LRWD1 predominantly during the G1 phase and with less affinity during mitosis, when phosphorylated.|||Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.|||Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication (By similarity).|||Nucleus|||Phosphorylated during mitosis.|||The BAH domain mediates binding to dimethylated histone H4 'Lys-20' (H4K20me2), which is enriched at replication origins. http://togogenome.org/gene/10090:Or8g4 ^@ http://purl.uniprot.org/uniprot/Q7TRA6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm20804 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Mas1 ^@ http://purl.uniprot.org/uniprot/P30554|||http://purl.uniprot.org/uniprot/Q0VB49 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts specifically as a functional antagonist of AGTR1 (angiotensin-2 type 1 receptor), although it up-regulates AGTR1 receptor levels. Positive regulation of AGTR1 levels occurs through activation of the G-proteins GNA11 and GNAQ, and stimulation of the protein kinase C signaling cascade. The antagonist effect on AGTR1 function is probably due to AGTR1 being physically altered by MAS1 (By similarity). Receptor for angiotensin 1-7.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with AGTR1. Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.|||Membrane http://togogenome.org/gene/10090:Cd59a ^@ http://purl.uniprot.org/uniprot/O55186 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in all tissues examined (liver, kidney, spleen, thymus, brain and heart). Low levels in thymus. Also expressed in mononuclear cells, erythrocytes and platelets. Barely detected in neutrophils.|||Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore (By similarity). http://togogenome.org/gene/10090:Naa10 ^@ http://purl.uniprot.org/uniprot/B1AUY9|||http://purl.uniprot.org/uniprot/Q3V4D5|||http://purl.uniprot.org/uniprot/Q540H0|||http://purl.uniprot.org/uniprot/Q9QY36 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoacetylated at Lys-136 which stimulates its catalytic activity.|||Belongs to the acetyltransferase family. ARD1 subfamily.|||Catalytic subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity (PubMed:12888564). Acetylates amino termini that are devoid of initiator methionine (By similarity). The alpha (N-terminal) acetyltransferase activity may be important for vascular, hematopoietic and neuronal growth and development (By similarity). Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation (PubMed:12464182). Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration (By similarity). Acetylates, and stabilizes TSC2, thereby repressing mTOR activity and suppressing cancer development (By similarity). Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX (By similarity). Acetylates HIST1H4A (By similarity). Acts as a negative regulator of sister chromatid cohesion during mitosis (By similarity).|||Cleaved by caspases during apoptosis.|||Component of the N-terminal acetyltransferase A complex (also called the NatA complex) composed of NAA10 and NAA15 (By similarity). Interacts with NAA15 (PubMed:12888564). Component of the N-terminal acetyltransferase A (NatA)/HYPK complex at least composed of NAA10, NAA15 and HYPK, which has N-terminal acetyltransferase activity (By similarity). In complex with NAA15, interacts with HYPK (By similarity). Component of the N-terminal acetyltransferase E (NatE) complex at least composed of NAA10, NAA15 and NAA50 (By similarity). Within the complex interacts with NAA15; the interaction is required for binding to NAAT50 (By similarity). Interacts with NAAT50 (By similarity). The interaction of the NatA complex with NAA50 reduces the acetylation activity of the NatA complex (By similarity). Component of the N-terminal acetyltransferase E (NatE)/HYPK complex at least composed of NAA10, NAA15, NAA50 and HYPK (By similarity). In complex with NAA15, interacts with HYPK; the interaction with HYPK reduces the capacity of the NatA complex to interact with NAA50 (By similarity). Interacts with HIF1A (via its ODD domain); the interaction increases HIF1A protein stability during normoxia, an down-regulates it when induced by hypoxia (PubMed:12464182). Interacts with the ribosome (By similarity). Binds to MYLK (By similarity). Interacts with NAA16 (By similarity). Interacts (via its C-terminal domain) with TSC2, leading to its acetylation (By similarity). Interacts with IKBKB (By similarity). Interacts with HSPA1A and HSPA1B leading to its acetylation (By similarity).|||Cytoplasm|||Expressed throughout the developing brain from 11.5 dpc through 17 dpc, continues to be expressed at P0, but then is down-regulated.|||Nucleus|||Phosphorylation by IKBKB/IKKB at Ser-209 destabilises NAA10 and promotes its proteasome-mediated degradation.|||Ubiquitous. http://togogenome.org/gene/10090:Tmem30b ^@ http://purl.uniprot.org/uniprot/Q0VEI2|||http://purl.uniprot.org/uniprot/Q8BHG3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate (Probable). Can mediate the export of alpha subunits ATP8A1, ATP8B1, ATP8B2 and ATP8B4 from the ER to the plasma membrane (By similarity).|||Belongs to the CDC50/LEM3 family.|||Cell membrane|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit (Probable). Interacts with alpha subunits ATP8A1, ATP8B1, ATP8B2 and ATP8B4 (By similarity). http://togogenome.org/gene/10090:Lrrtm4 ^@ http://purl.uniprot.org/uniprot/Q80XG9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRTM family.|||Cell membrane|||May play a role in the development and maintenance of the vertebrate nervous system. Exhibits strong synaptogenic activity, restricted to excitatory presynaptic differentiation (By similarity).|||Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including LRRTM4. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.|||Postsynaptic cell membrane|||Predominantly in the brain (at protein level). Also expressed in the cerebellum and other tissues. http://togogenome.org/gene/10090:Agtr2 ^@ http://purl.uniprot.org/uniprot/P35374|||http://purl.uniprot.org/uniprot/Q3US12 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed at highest levels in adrenal gland and uterus.|||Helix VIII may act as a gatekeeper for either suppression or activation of the receptor, depending on post-translational modifications and interactions with various receptor partners. Helix VIII is found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G-proteins or beta-arrestins. Upon switching to a membrane-bound conformation, helix VIII can support the recruitment of G proteins and beta-arrestins.|||Interacts with MTUS1.|||Membrane|||Receptor for angiotensin II, a vasoconstricting peptide (PubMed:8726696). Signals primarily via a non-canonical G-protein- and beta-arrestin independent pathways (By similarity). Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation (PubMed:15539617). http://togogenome.org/gene/10090:Or8j3c ^@ http://purl.uniprot.org/uniprot/Q7TR71 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd55b ^@ http://purl.uniprot.org/uniprot/E9Q731|||http://purl.uniprot.org/uniprot/E9QAP4|||http://purl.uniprot.org/uniprot/Q61476 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the receptors of complement activation (RCA) family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Testis, spleen and lymph node.|||The first Sushi domain (SCR1) is not necessary for function. SCR2 and SCR4 provide the proper conformation for the active site on SCR3 (By similarity).|||This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade. Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage. http://togogenome.org/gene/10090:Slc22a6 ^@ http://purl.uniprot.org/uniprot/Q8VC69 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basal cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Developmentally regulated with significant expression beginning at 18 dpc and rising just before birth.|||Expressed in kidney (PubMed:9045672, PubMed:9880528, PubMed:15944205). In kidney, restricted to the proximal convoluted tubule (representing S1 and S2 segments) (PubMed:9045672, PubMed:15944205). In brain, expressed in neurons of the cortex cerebri and hippocampus as well as in the ependymal cell layer of the choroid plexus (PubMed:9045672, PubMed:15944205).|||Glycosylated. Glycosylation is necessary for proper targeting of the transporter to the plasma membrane.|||Involved in the renal transport of a variety of drugs with well-known nephrotoxic potential, therefore may play a role in the etiology of the drug-associated nephrotoxicity (By similarity). Uptakes the diagnostic agent PAH/para-aminohippurate and clinically used drugs (PubMed:9045672, PubMed:9880528, PubMed:10744714, PubMed:14979872, PubMed:14749323). Mediates the bidirectional transport of PAH/para-aminohippurate (By similarity).|||Multiple cysteine residues are necessary for proper targeting to the plasma membrane.|||Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:15944205). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (By similarity). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (By similarity). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (By similarity). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) (PubMed:15944205). May transport glutamate. Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (By similarity). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA) and 3-carboxy-4- methyl-5-propyl-2-furanpropionate(CMPF) and urate (By similarity). Xenobiotics include the mycotoxin ochratoxin (OTA) (By similarity). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (By similarity). http://togogenome.org/gene/10090:Mro ^@ http://purl.uniprot.org/uniprot/Q7TNB4 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ First detected in the developing male gonad before overt testis differentiation. By 12.5 dpc, expression is restricted to the developing testis cords and its expression is not germ cell-dependent. No expression seen in female gonads between 10.5 and 14.5 dpc.|||Prominent expression seen in testis, brain, liver and heart. Weakly expressed in the kidney.|||nucleolus http://togogenome.org/gene/10090:Bcor ^@ http://purl.uniprot.org/uniprot/Q8CGN4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BCOR family.|||Expressed in heart, liver, lung, skeletal muscle, spleen and testis.|||Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Isoform 1 may interact with MLLT3/AF9 (PubMed:12776190). Interacts with BCL6; the interaction is direct. Forms ternary complexes with BCL6 and SMRT/NCOR2 on selected target genes promoters; potently repress expression. Can interact with HDAC1, HDAC3 and HDAC5. Interacts with PCGF1; the interaction is direct. Interacts with KDM2B. Component of an approximately 800 kDa repressive BCOR complex at least composed of BCOR, RYBP, PCGF1, RING1, RNF2/RING2, KDM2B and SKP1 (By similarity).|||Nucleus|||Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as BCL6 and MLLT3. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor. Involved in the repression of TFAP2A; impairs binding of BCL6 and KDM2B to TFAP2A promoter regions. Via repression of TFAP2A acts as a negative regulator of osteo-dentiogenic capacity in adult stem cells; the function implies inhibition of methylation on histone H3 'Lys-4' (H3K4me3) and 'Lys-36' (H3K36me2) (By similarity). http://togogenome.org/gene/10090:Ttyh1 ^@ http://purl.uniprot.org/uniprot/Q9D3A9 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Aberrant splicing.|||Belongs to the tweety family.|||Cell membrane|||Probable chloride channel. May be involved in cell adhesion (By similarity).|||Restricted mainly to neural tissues. Strongly expressed in brain and eye. http://togogenome.org/gene/10090:Aph1c ^@ http://purl.uniprot.org/uniprot/Q9DCZ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APH-1 family.|||Membrane|||Potential component of the gamma-secretase complex.|||Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). http://togogenome.org/gene/10090:Sec22b ^@ http://purl.uniprot.org/uniprot/O08547 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synaptobrevin family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Interacts with STX17. Component of two distinct SNARE complexes consisting of STX5, GOSR2/BOS1, BET1 and SEC22B or STX18, USE1L, BNIP1/SEC20L and SEC22B. YKT6 can probably replace SEC22B as subunit of either complex (By similarity). Interacts with the COPII Sec23/24 complex composed of SEC23A and SEC24A; recruits SEC22B into COPII-coated vesicles to allow its transport from the endoplasmic reticulum to the Golgi (By similarity).|||Melanosome|||SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER.|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Atp2b2 ^@ http://purl.uniprot.org/uniprot/F8WHB1|||http://purl.uniprot.org/uniprot/Q3UHH0|||http://purl.uniprot.org/uniprot/Q3UHJ3|||http://purl.uniprot.org/uniprot/Q9R0K7 ^@ Caution|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-driven Ca(2+) ion pump involved in the maintenance of basal intracellular Ca(2+) levels in specialized cells of cerebellar circuit and vestibular and cochlear systems (PubMed:17234811, PubMed:9668038). Uses ATP as an energy source to transport cytosolic Ca(2+) ions across the plasma membrane to the extracellular compartment. Has fast activation and Ca(2+) clearance rate suited to control fast neuronal Ca(2+) dynamics (PubMed:17409239, PubMed:20083513). At parallel fiber to Purkinje neuron synapse, mediates presynaptic Ca(2+) efflux in response to climbing fiber-induced Ca(2+) rise. Provides for fast return of Ca(2+) concentrations back to their resting levels, ultimately contributing to long-term depression induction and motor learning (PubMed:17409239, PubMed:20083513). Plays an essential role in hearing and balance. In cochlear hair cells, shuttles Ca(2+) ions from stereocilia to the endolymph and dissipates Ca(2+) transients generated by the opening of the mechanoelectrical transduction channels. Regulates Ca(2+) levels in the vestibular system, where it contributes to the formation of otoconia (PubMed:9668038) (By similarity). Regulates Ca(2+) signaling through dissipation of Ca(2+) transients generated by store-operated channels (By similarity). In lactating mammary gland, allows for the high content of Ca(2+) ions in the milk (PubMed:15302868).|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.|||Catalyzes the hydrolysis of ATP coupled with the transport of calcium.|||Cell membrane|||Defects in Atp2b2 are associated with early onset profound hearing loss and severe vestibular dysfunction.|||Expressed in the retina, with strongest levels in the inner plexiform layer, weaker levels in the outer plexiform layer, and very low levels in the proximal inner nuclear layer (PubMed:12209837). Specifically expressed in the following retinal cell types: rod bipolar cells, horizontal cells, amacrine cells and ganglion cells (PubMed:12209837). Also found in the cochlea (stereocilia and outer wall of hair cells) (at protein level) (PubMed:9697703). Strongly expressed in brain cortex and cerebellum. Found at low levels in heart, liver, lung and testis during late gestation (PubMed:9697703, PubMed:20083513). Expressed in lactating mammary gland (at protein level).|||Interacts with PDZD11.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mutant mice, born at the expected Mendelian rate, show balance impairment and hearing loss. They develop severe ataxia before 2 weeks of age associated with the absence of otoconia in the vestibular inner ear.|||Synapse http://togogenome.org/gene/10090:Tmem276-zftraf1 ^@ http://purl.uniprot.org/uniprot/P0DW86|||http://purl.uniprot.org/uniprot/P0DW87 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZFTRAF1 family.|||Cytoplasm|||Expressed in heart, brain, liver, testis and kidney.|||Interacts with LGALS3.|||Membrane|||perinuclear region http://togogenome.org/gene/10090:Phax ^@ http://purl.uniprot.org/uniprot/G5E8V8|||http://purl.uniprot.org/uniprot/Q9JJT9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus. Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner. Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Binds also to telomerase RNA (By similarity).|||Belongs to the PHAX family.|||Cajal body|||Cytoplasm|||Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Part of a precomplex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20 and m7G-capped RNA. Interacts with NCBP1/CBP80. Found in a complex with snoRNA. Interacts with NCBP2/CBP20 (By similarity).|||Nucleus|||Phosphorylated in the nucleus. Dephosphorylated in the cytoplasm.|||nucleoplasm http://togogenome.org/gene/10090:Wdr26 ^@ http://purl.uniprot.org/uniprot/Q8C6G8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Forms homooligomers. Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with DDB1-CUL4A/B E3 ligase complexes. Forms a complex composed of at least WDR26, a G-beta:gamma unit, and PLCB2. Interacts with AXIN1.|||G-beta-like protein involved in cell signal transduction. Acts as a negative regulator in MAPK signaling pathway. Functions as a scaffolding protein to promote G beta:gamma-mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes. Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (By similarity). Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta-catenin destruction complex, thus negatively regulating CTNNB1 degradation. Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration. Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria (By similarity). Protects also cells by promoting hypoxia-mediated autophagy and mitophagy (By similarity).|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Nxn ^@ http://purl.uniprot.org/uniprot/P97346 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the phosphatase 2A holoenzyme. Interacts with PPP2CA; the interaction is direct. Interacts with DVL1 (via PDZ domain); the interaction is direct and regulated by oxidative stress.|||Belongs to the nucleoredoxin family.|||Functions as a redox-dependent negative regulator of the Wnt signaling pathway, possibly by preventing ubiquitination of DVL3 by the BCR(KLHL12) complex. May also function as a transcriptional regulator act as a regulator of protein phosphatase 2A (PP2A).|||Nucleus|||Perinatal lethality, possibly due abnormal cardiovascular development. Osteoblasts show an aberrant activation of the Wnt signaling pathway.|||Specifically expressed form 9.5 dpc to 12.5 dpc in limb buds.|||Widely expressed with higher expression in testis and skin.|||cytosol http://togogenome.org/gene/10090:Igfbp7 ^@ http://purl.uniprot.org/uniprot/Q61581 ^@ Function|||Induction|||RNA Editing|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds IGF-I and IGF-II with a relatively low affinity Stimulates prostacyclin (PGI2) production. Stimulates cell adhesion (By similarity).|||By retinoic acid.|||Expressed at high levels in lung, kidney, small intestine, testis and uterus and at moderate levels in liver.|||Partially edited. Position 77 seems to be edited at about 56% and position 94 at about 58%.|||Secreted http://togogenome.org/gene/10090:Ces2h ^@ http://purl.uniprot.org/uniprot/F6Z9B9 ^@ Similarity ^@ Belongs to the type-B carboxylesterase/lipase family. http://togogenome.org/gene/10090:Ckmt1 ^@ http://purl.uniprot.org/uniprot/P30275|||http://purl.uniprot.org/uniprot/Q545N7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP:guanido phosphotransferase family.|||Exists as an octamer composed of four MTCK homodimers.|||Mitochondrial creatine kinase binds cardiolipin.|||Mitochondrion inner membrane|||Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. http://togogenome.org/gene/10090:Hoxa2 ^@ http://purl.uniprot.org/uniprot/P31245 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family. Proboscipedia subfamily.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:H2ac21 ^@ http://purl.uniprot.org/uniprot/Q64522 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Ptpru ^@ http://purl.uniprot.org/uniprot/B1AUH1 ^@ Developmental Stage|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.|||Cell junction|||Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Expressed throughout embryonic development. First detected at 7 dpc.|||Forms homooligomeric complexes which mediate cell homotypic adhesion (Probable). Interacts (via the cytoplasmic juxtamembrane domain) with CTNNB1; may mediate interaction with the cadherin/catenin adhesion complex. Interacts with KIT (By similarity). May interact with AP3B1 (By similarity).|||Intron retention.|||N-glycosylated.|||Phosphorylated on tyrosine residues upon activation of KIT with stem cell factor (SCF). The 73 kDa proteolytic product is not phosphorylated (By similarity).|||The extracellular domain is proteolytically processed through cleavage within the fibronectin type-III 4 domain. In addition to the 190 kDa full-length protein, proteolytic products of 100 kDa, 80 kDa and 73 kDa are observed (By similarity).|||Transcripts of different sizes are differentially expressed in a subset of tissues. Detected in brain, lung, skeletal muscle, heart, kidney and placenta. In brain; expressed in olfactory bulb, cerebral cortex, hippocampus and cerebellum.|||Tyrosine-protein phosphatase which dephosphorylates CTNNB1. Regulates CTNNB1 function both in cell adhesion and signaling. May function in cell proliferation and migration and play a role in the maintenance of epithelial integrity. May play a role in megakaryocytopoiesis (By similarity). http://togogenome.org/gene/10090:Tia1 ^@ http://purl.uniprot.org/uniprot/P52912 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ 50% lethality between embryonic day 16.5 and 3 weeks of age (PubMed:10921895). Surviving mice appear normal and live for around 2 years (PubMed:10921895). Increased production of TNF in macrophages after stimulation with lipopolysaccharides (LPS) (PubMed:10921895). Increased susceptibility to LPS-induced endotoxic shock (PubMed:10921895).|||Cytoplasm|||Homooligomer; homooligomerization is induced by Zn(2+) (PubMed:29298433). Interacts with FASTK; the interactions leads to its phosphorylation (By similarity). Interacts (via RRM1 and the C-terminal glutamine-rich (Q) sequence) with SNRPC/U1-C (via N-terminus); thereby facilitating spliceosomal U1 snRNP recruitment to 5' splice sites (By similarity).|||Nucleus|||Phosphorylatedby FASTK; phosphorylation occurs after FAS ligation in FAS-mediated apoptosis and before DNA fragmentation.|||RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences (PubMed:10938105, PubMed:16227602). Binds to U-rich sequences immediately downstream from a 5' splice sites in a uridine-rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion, thereby modulating alternative pre-RNA splicing (PubMed:10938105). Preferably binds to the U-rich IAS1 sequence in a U1 snRNP-dependent manner; this binding is optimal if a 5' splice site is adjacent to IAS1 (PubMed:10938105). Activates the use of heterologous 5' splice sites; the activation depends on the intron sequence downstream from the 5' splice site, with a preference for a downstream U-rich sequence (PubMed:10938105). By interacting with SNRPC/U1-C, promotes recruitment and binding of spliceosomal U1 snRNP to 5' splice sites followed by U-rich sequences, thereby facilitating atypical 5' splice site recognition by U1 snRNP (By similarity). Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIAR mRNA (PubMed:11514562). Acts as a modulator of alternative splicing for the apoptotic FAS receptor, thereby promoting apoptosis (By similarity). Binds to the 5' splice site region of FAS intron 5 to promote accumulation of transcripts that include exon 6 at the expense of transcripts in which exon 6 is skipped, thereby leading to the transcription of a membrane-bound apoptotic FAS receptor, which promotes apoptosis (By similarity). Binds to a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of COL2A1 exon 2 (By similarity). Also binds to the equivalent AT-rich element in COL2A1 genomic DNA, and may thereby be involved in the regulation of transcription (By similarity). Involved in the repression of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs), including target ARE-bearing mRNAs encoding TNF and PTGS2 (PubMed:16227602, PubMed:10921895). Also participates in the cellular response to environmental stress, by acting downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SGs), leading to stress-induced translational arrest (By similarity). Formation and recruitment to SGs is regulated by Zn(2+) (PubMed:29298433). Possesses nucleolytic activity against cytotoxic lymphocyte target cells (By similarity).|||Stress granule|||The C-terminal glutamine-rich (Q) sequence in combination with the RRM 1 domain is required for the interaction with SNRPC/U1-C and to facilitate recruitment of spliceosomal U1 snRNP to 5' splice sites.|||The RNA recognition motif domains RRM 2 and RRM 3 are necessary and sufficient for binding to uridine-rich target pre-mRNA.|||The RRM 1 and RRM 2 domains are required for the localization to stress granules (SGs) and for the recruitment of TIAR1 and poly(A) RNA to SGs in response to stress.|||The RRM2 domain and the C-terminal residues 287-340 contribute to nuclear localization.|||The RRM3 domain mediates nuclear export. http://togogenome.org/gene/10090:Plpp6 ^@ http://purl.uniprot.org/uniprot/Q9D4F2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Endoplasmic reticulum membrane|||Magnesium-independent polyisoprenoid diphosphatase that catalyzes the sequential dephosphorylation of presqualene, farnesyl, geranyl and geranylgeranyl diphosphates. Functions in the innate immune response through the dephosphorylation of presqualene diphosphate which acts as a potent inhibitor of the signaling pathways contributing to polymorphonuclear neutrophils activation. May regulate the biosynthesis of cholesterol and related sterols by dephosphorylating presqualene and farnesyl diphosphate, two key intermediates in this biosynthetic pathway. May also play a role in protein prenylation by acting on farnesyl diphosphate and its derivative geranylgeranyl diphosphate, two precursors for the addition of isoprenoid anchors to membrane proteins. Has a lower activity towards phosphatidic acid (PA), but through phosphatidic acid dephosphorylation may participate in the biosynthesis of phospholipids and triacylglycerols. May also act on ceramide-1-P, lysophosphatidic acid (LPA) and sphing-4-enine 1-phosphate/sphingosine-1-phosphate.|||Nucleus envelope|||Nucleus inner membrane|||Phosphorylation by PKC activates the phosphatase activity towards presqualene diphosphate. http://togogenome.org/gene/10090:Serpine2 ^@ http://purl.uniprot.org/uniprot/Q07235|||http://purl.uniprot.org/uniprot/Q543R5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Most abundant in seminal vesicles.|||Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin.|||extracellular space http://togogenome.org/gene/10090:Clec2h ^@ http://purl.uniprot.org/uniprot/Q8C1T8 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Detected in ileum, liver, kidney and in IL2-activated natural killer cells.|||Lectin-type cell surface receptor. http://togogenome.org/gene/10090:Muc19 ^@ http://purl.uniprot.org/uniprot/Q6PZE0 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||May function in ocular mucus homeostasis.|||Secreted|||Specifically expressed in sublingual salivary glands. Expressed by mucous cells of the submandibular gland and submucosal gland of the trachea. Expression is altered in sld (sublingual gland differentiation arrest) mutants. http://togogenome.org/gene/10090:Ang5 ^@ http://purl.uniprot.org/uniprot/Q5GAN1 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Shfl ^@ http://purl.uniprot.org/uniprot/Q3U076|||http://purl.uniprot.org/uniprot/Q8CAK3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SHFL family.|||Cytoplasm|||Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses and cellular genes. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site. May exhibit antiviral activity.|||Interacts with PABPC1. Found in a complex with PABPC1 and LARP1. Interacts with ELAV1, MOV10 and UPF1; the interactions increase in presence of RNA. Binds to ribosomes. Interacts with GSPT1.|||Nucleus|||P-body http://togogenome.org/gene/10090:Or6d14 ^@ http://purl.uniprot.org/uniprot/Q8VG27 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cblc ^@ http://purl.uniprot.org/uniprot/G3X9U0|||http://purl.uniprot.org/uniprot/Q80XL1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subunit|||Tissue Specificity ^@ Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-424', has the highest ubiquitin ligase activity among CBL family proteins. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival.|||Autoubiquitinated, when phosphorylated at Tyr-340.|||E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.|||EF-hand-like and Sh2-like domains are required for N-terminal inhibition of E3 activity.|||Expressed at 14.5 dpc in liver, lung and brain.|||Interacts with Ubiquitin-conjugating enzyme E2 UBE2D2 and UBE2D3. Isoform 1 interacts with EGFR (tyrosine phosphorylated). Interacts with the SH3 domain proteins LYN and CRK. Interacts (via RING-type zinc finger) with TGFB1I1 (via LIM zinc-binding domain 2); the interaction is direct and enhances the E3 activity. Interacts directly with RET (inactive) and CD2AP; dissociates from RET upon RET activation by GDNF which also increases the interaction with CD2AP suggesting dissociation as CBLC:CD2AP complex. Interacts with SRC; the interaction is enhanced when SRC is phosphorylated at 'Tyr-419'.|||No visible phenotype.|||Phosphorylated on multiple tyrosine residues by SRC. Isoform 1, but not isoform 2, is phosphorylated on tyrosines by EGFR.|||Phosphorylated on tyrosines by EGFR.|||Phosphorylation at Tyr-340 is necessary and sufficient for the activation of E3 activity.|||The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.|||The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.|||This protein has one functional calcium-binding site.|||Widely expressed in tissues, where the expression is restricted to epithelial cells (at protein level). http://togogenome.org/gene/10090:Clk1 ^@ http://purl.uniprot.org/uniprot/P22518 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylates on all three types of residues.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.|||Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates (PubMed:1825055, PubMed:1986248, PubMed:9307018). Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1 (PubMed:8617202, PubMed:9307018). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (By similarity).|||Interacts with PPIG and UBL5.|||Lacks the kinase domain.|||Nucleus|||Regulates splicing of its own pre-mRNA according to its kinase activity; increased expression of the catalytically active form influences splicing to generate the catalytically inactive splicing variant lacking the kinase domain. Leucettine L41 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins. http://togogenome.org/gene/10090:Lrrc75b ^@ http://purl.uniprot.org/uniprot/Q7TPD7 ^@ Function|||Induction|||Similarity ^@ Belongs to the LRRC75 family.|||Markedly decreased during differentiation.|||May suppress myogenic differentiation by modulating MYOG expression and Erk1/2 signaling. http://togogenome.org/gene/10090:Or14j9 ^@ http://purl.uniprot.org/uniprot/Q8C0S2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem115 ^@ http://purl.uniprot.org/uniprot/Q543Y8|||http://purl.uniprot.org/uniprot/Q9WUH1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM115 family.|||Golgi stack membrane|||Homooligomer. Interacts with COPB1. May interact with LMAN1. Interacts with the COG complex; probably through COG3.|||May play a role in retrograde transport of proteins from the Golgi to the endoplasmic reticulum. May indirectly play a role in protein glycosylation in the Golgi.|||Membrane http://togogenome.org/gene/10090:Tmem17 ^@ http://purl.uniprot.org/uniprot/Q8K0U3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM17 family.|||Part of the tectonic-like complex (also named B9 complex).|||Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling.|||cilium membrane http://togogenome.org/gene/10090:Steap3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1G9|||http://purl.uniprot.org/uniprot/E9QN92|||http://purl.uniprot.org/uniprot/Q8CI59 ^@ Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STEAP family.|||Defects in Steap3 are the cause of fragile-red phenotype characterized by hypochromic microcytic anemia.|||Endosome membrane|||Glycosylated.|||Highly expressed in fetal liver (the site of midgestational hematopoiesis).|||Homodimer. Interacts with BNIP3L, MYT1, RHBDL4/RHBDD1 and TCTP (By similarity).|||Integral membrane protein that functions as NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane (PubMed:16227996, PubMed:16609065, PubMed:18955558). Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (By similarity). Can also reduce Cu(2+) to Cu(1+) (PubMed:16609065). Mediates efficient transferrin-dependent iron uptake in erythroid cells (PubMed:16227996). May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression (By similarity). Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP (By similarity).|||Membrane|||Mice display iron deficiency anemia, due to a defect in iron release through the transferrin cycle.|||Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage occurs at multiple sites in a glycosylation-independent manner (By similarity). http://togogenome.org/gene/10090:Mrgpra9 ^@ http://purl.uniprot.org/uniprot/A0A140T8U8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane http://togogenome.org/gene/10090:Ctnna3 ^@ http://purl.uniprot.org/uniprot/Q65CL1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the vinculin/alpha-catenin family.|||Expressed in heart (at protein level).|||Interacts with CTNNB1 (PubMed:11590244). Interacts with PKP2 (By similarity).|||May be involved in formation of stretch-resistant cell-cell adhesion complexes.|||cytoskeleton|||desmosome http://togogenome.org/gene/10090:Zfp629 ^@ http://purl.uniprot.org/uniprot/Q6A085 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Pea15a ^@ http://purl.uniprot.org/uniprot/Q62048 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds RPS6KA3, MAPK3 and MAPK1. Interacts with CASP8 and FADD (By similarity). Transient interaction with PLD1 and PLD2.|||Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm. Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface (By similarity).|||Cytoplasm|||Increases PLD1 and PLD2 levels, possibly by stabilizing the protein.|||Phosphorylated by protein kinase C and calcium-calmodulin-dependent protein kinase. These phosphorylation events are modulated by neurotransmitters or hormones.|||Predominantly expressed in the brain. Low levels in some peripheral organs. http://togogenome.org/gene/10090:Colec11 ^@ http://purl.uniprot.org/uniprot/Q3SXB8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the COLEC10/COLEC11 family.|||Highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies.|||Homotrimer; disulfide-linked. Interacts with MASP1; probably triggers the lectin pathway of complement.|||Lectin that plays a role in innate immunity, apoptosis and embryogenesis. Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope. Primarily recognizes the terminal disaccharide of the glycan. Also recognizes a subset of fucosylated glycans and lipopolysaccharides. Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1. Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding. Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis.|||Secreted http://togogenome.org/gene/10090:Aqp3 ^@ http://purl.uniprot.org/uniprot/Q8R2N1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Basolateral cell membrane|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Detected in principal cells in collecting ducts in kidney medulla (at protein level) (PubMed:16641094). Renal medulla and colon. Predominantly in the inner medulla. Expressed in basal layer of epidermal keratinocytes.|||Mice have dry skin with reduced SC (stratum corneum) hydration, decreased elasticity and impaired biosynthesis. The glycerol content of SC and epidermis is reduced, whereas that of dermis and serum is normal. The dry, relatively inelastic skin is probably related to the humectant properties of glycerol, and the impaired SC repair to impaired epidermal biosynthetic function.|||Water channel required to promote glycerol permeability and water transport across cell membranes. Acts as a glycerol transporter in skin and plays an important role in regulating SC (stratum corneum) and epidermal glycerol content. Involved in skin hydration, wound healing, and tumorigenesis. Provides kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Slightly permeable to urea and may function as a water and urea exit mechanism in antidiuresis in collecting duct cells. It may play an important role in gastrointestinal tract water transport and in glycerol metabolism. http://togogenome.org/gene/10090:Cldn6 ^@ http://purl.uniprot.org/uniprot/Q0GH64|||http://purl.uniprot.org/uniprot/Q9Z262 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Cell membrane|||Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3 (PubMed:10601346). Interacts with CLDN1, CD81 and OCLN (By similarity).|||Expressed mostly in embryonic tissues.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Ntrk1 ^@ http://purl.uniprot.org/uniprot/Q3UFB7 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Early endosome membrane|||Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Homodimerization is induced by binding of a NGF dimer (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a nerve growth factor (NGF)-dependent manner. Interacts with RAPGEF2; the interaction is strengthened after NGF stimulation. Interacts with SQSTM1; bridges NTRK1 to NGFR. Forms a ternary complex with NGFR and KIDINS220; this complex is affected by the expression levels of KIDINS220 and an increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1. Interacts (phosphorylated upon activation by NGF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by NGF) with PLCG1; mediates PLCG1 phosphorylation and activation. Interacts (phosphorylated) with SH2B1 and SH2B2. Interacts with GRB2. Interacts with PIK3R1. Interacts with FRS2. Interacts with SORT1; may regulate NTRK1 anterograde axonal transport (By similarity). Interacts with SH2D1A; regulates NTRK1 (PubMed:16223723). Interacts with NRADD. Interacts with RAB7A. Interacts with PTPRS (By similarity). Interacts with USP36; USP36 does not deubiquitinate NTRK1 (By similarity). Interacts with GGA3 (By similarity).|||Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain.|||First detected at 13.5 dpc, a time coinciding with the requirement of sympathetic neurons for NGF.|||Late endosome membrane|||Ligand-mediated autophosphorylation. Interaction with SQSTM1 is phosphotyrosine-dependent. Autophosphorylation at Tyr-499 mediates interaction and phosphorylation of SHC1.|||Mice die early after birth due to severe sensory and sympathetic neuropathies characterized by extensive neuronal cell loss in trigeminal, sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic basal forebrain projections to the hippocampus and cortex. There are for instance 35% fewer cells by 17.5 dpc in the superior cervical ganglion, a major component of the sympathetic system.|||N-glycosylated.|||Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.|||Recycling endosome membrane|||The extracellular domain mediates interaction with NGFR.|||The pro-survival signaling effect of NTRK1 in neurons requires its endocytosis into signaling early endosomes and its retrograde axonal transport. This is regulated by different proteins including CFL1, RAC1 and SORT1. NTF3 is unable to induce this signaling probably due to the lability of the NTF3-NTRK1 complex in endosomes. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. Regulated by NGFR.|||The transmembrane domain mediates interaction with KIDINS220.|||Ubiquitinated (PubMed:16113645). Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination by NEDD4L leads to degradation (By similarity). Ubiquitination regulates the internalization of the receptor (PubMed:16113645). http://togogenome.org/gene/10090:Or5m3 ^@ http://purl.uniprot.org/uniprot/A2ATE5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vma21 ^@ http://purl.uniprot.org/uniprot/F2Z446|||http://purl.uniprot.org/uniprot/F2Z447|||http://purl.uniprot.org/uniprot/Q78T54 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the V0 complex of the vacuolar ATPase (V-ATPase) (By similarity). Interacts with ATP6AP2 (By similarity).|||Associates with the V0 complex of the vacuolar ATPase (V-ATPase).|||Belongs to the VMA21 family.|||COPII-coated vesicle membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum. http://togogenome.org/gene/10090:Mmp12 ^@ http://purl.uniprot.org/uniprot/P34960|||http://purl.uniprot.org/uniprot/Q3TCW6 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 4 Ca(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3 (By similarity).|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix http://togogenome.org/gene/10090:Lyrm2 ^@ http://purl.uniprot.org/uniprot/Q8R033 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the complex I LYR family.|||Involved in effecient integration of the N-module into mitochondrial respiratory chain complex I.|||Mitochondrion http://togogenome.org/gene/10090:Foxd2 ^@ http://purl.uniprot.org/uniprot/O35392 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at high levels in the ventral region of newly formed somites, in sclerotomal derivatives, in lateral plate and cephalic mesoderm and in the first and second branchial arches. Other regions of mesodermal expression include the developing tongue, meninges, nose, whiskers, kidney, genital tubercule and limb joints. In the nervous system it is transcribed in restricted regions of the mid- and forebrain.|||Nucleus|||Probable transcription factor involved in embryogenesis and somatogenesis. http://togogenome.org/gene/10090:Klk4 ^@ http://purl.uniprot.org/uniprot/Q9Z0M1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Has a major role in enamel formation. Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix.|||In developing teeth, expressed in ameloblasts during transition and maturation stages (PubMed:10863090, PubMed:10690663, PubMed:19578120). Expressed weakly in odontoblasts (PubMed:10863090). Not detected in odontoblasts (PubMed:19578120). Detected in the epithelium surrounding the erupted first molar (PubMed:10690663).|||N-glycosylated. The N-glycan structures are of complex diantennary or triantennary type, which may be further modified with up to 2 sialic acid residues.|||Secreted|||Viable and fertile, when reared on a soft diet. Tooth morphology is grossly normal but the enamel surface is fragile and rapidly abraded. Although formation of the enamel layer is initially normal, the crystallites fail to thicken and interlock. The enamel proteins enamelin and amelogenin are not cleared and persist in the matrix during the maturation stage. http://togogenome.org/gene/10090:Or4p21 ^@ http://purl.uniprot.org/uniprot/Q7TR17 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp451 ^@ http://purl.uniprot.org/uniprot/Q8C0P7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds UBE2I/UBC9 and two SUMO2 molecules via its N-terminus. The most N-terminal region interacts with the SUMO2 chain that is covalently bound to the UBE2I/UBC9 active site, while the second region interacts with another SUMO2 that is non-covalently associated with the same UBE2I/UBC9 chain.|||E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins. Plays a role in protein SUMO2 modification in response to stress caused by DNA damage and by proteasome inhibitors (in vitro). Required for MCM4 sumoylation. Has no activity with SUMO1 (PubMed:26524493). Preferentially transfers an additional SUMO2 chain onto the SUMO2 consensus site 'Lys-11'. Negatively regulates transcriptional activation mediated by the SMAD4 complex in response to TGF-beta signaling. Inhibits EP300-mediated acetylation of histone H3 at 'Lys-9'. Plays a role in regulating the transcription of AR targets (By similarity).|||Homooligomer. Interacts (via N-terminal region) with SUMO1. Interacts (via N-terminal region) with SUMO2. Interacts simultaneously with two SUMO2 chains. Identified in a complex with SUMO2 and UBE2I/UBC9, where one ZNF451 interacts with one UBE2I/UBC9 and two SUMO2 chains, one bound to the UBE2I/UBC9 active site and the other to another region of the same UBE2I/UBC9 molecule. Interacts (via C-terminus) with ubiquitin. Interacts (via N-terminal zinc-finger domains) with SMAD4 (via MH2 domain). Interacts with SMAD2 and SMAD3. Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4. Interacts with EP300. Inhibits interaction between EP300 and the SMAD4 complex. Interacts with SIMC1.|||Nucleus|||PML body|||Sumoylated. Predominantly sumoylated on the N-terminal region that is important for interaction with SUMO1 and SUMO2. Sumoylation is important for localization in nuclear granules; desumoylation leads to diffuse nucleoplasmic location. Autosumoylated (in vitro). Sumoylation enhances E3 SUMO-protein ligase activity.|||nucleoplasm http://togogenome.org/gene/10090:Hax1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JE46|||http://purl.uniprot.org/uniprot/A0A0G2JFF9|||http://purl.uniprot.org/uniprot/B9EJR4|||http://purl.uniprot.org/uniprot/O35387|||http://purl.uniprot.org/uniprot/Q3UXX9|||http://purl.uniprot.org/uniprot/Q8R5I5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HAX1 family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Endoplasmic reticulum|||Interacts with ABCB1, ABCB4 and ABCB11 (By similarity). Directly associates with HCLS1/HS1, through binding to its N-terminal region (By similarity). Interacts with CTTN (PubMed:10760273). Interacts with PKD2(PubMed:10760273). Interacts with GNA13. Interacts with CASP9. Interacts with ITGB6. Interacts with PLN and ATP2A2; these interactions are inhibited by calcium. Interacts with GRB7. Interacts (via C-terminus) with XIAP/BIRC4 (via BIR 2 domain and BIR 3 domain) and this interaction blocks ubiquitination of XIAP/BIRC4. Interacts with TPC2. Interacts with KCNC3 (PubMed:26997484). Interacts with XPO1 (By similarity). Interacts with RNF217 (By similarity). Interacts with UCP3; the interaction is direct and calcium-dependent (PubMed:26915802).|||Mice lacking Hax1 fail to survive longer than 14 weeks, due to a loss of motor coordination and activity, leading to failure to eat and drink. They display extensive apoptosis of neurons in the striatum and cerebellum, and a loss of lymphocytes in spleen, bone marrow and thymus.|||Mitochondrion matrix|||Nucleus|||Nucleus membrane|||P-body|||Recruits the Arp2/3 complex to the cell cortex and regulates reorganization of the cortical actin cytoskeleton via its interaction with KCNC3 and the Arp2/3 complex. Slows down the rate of inactivation of KCNC3 channels. Promotes GNA13-mediated cell migration. Involved in the clathrin-mediated endocytosis pathway. May be involved in internalization of ABC transporters such as ABCB11. May inhibit CASP9 and CASP3. Promotes cell survival. May regulate intracellular calcium pools.|||Sarcoplasmic reticulum|||Ubiquitous, with highest levels in kidney and liver (at protein level).|||cell cortex http://togogenome.org/gene/10090:Sirt4 ^@ http://purl.uniprot.org/uniprot/Q8R216 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to some authors, ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant.|||Acts as NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:19220062). Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner (PubMed:25525879). Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest (PubMed:16959573). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation (PubMed:23663782). Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis (PubMed:23746352). Does not seem to deacetylate PC (PubMed:23438705). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1-PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310, PubMed:20685656). Down-regulates insulin secretion (By similarity).|||Belongs to the sirtuin family. Class II subfamily.|||Binds 1 zinc ion per subunit.|||Detected in kidney, heart, brain, liver and pancreatic islets (at protein level).|||Expression is directly activated by ATF4/CREB2. In response to mTORC1 signal, expression is down-regulated due to degradation of ATF4/CREB2 (PubMed:23663782). Induced following DNA damage (PubMed:23562301). The expression is strongly inhibited by fasting (PubMed:24043310).|||Interacts with IDE and SLC25A5 (By similarity). Interacts with GLUD1 (PubMed:16959573). Interacts with DLAT and PDHX (By similarity). Interacts with MCCC1 (via the biotin carboxylation domain) (PubMed:23438705). Interacts with PCCA and PC (PubMed:23438705).|||Mitochondrion matrix|||No visible phenotype. Decreased mitochondrial protein ADP-ribosylation. Increased plasma insulin levels. Mice develop lung tumors more frequently. Defects in lipid metabolism, leading to increased protection against diet-induced obesity. Animals show higher levels of NAD(+) in liver (PubMed:24043310). In the hepatic periportal zone, decreased number of mitochondria with an increase in their length (PubMed:24043310). http://togogenome.org/gene/10090:Col6a2 ^@ http://purl.uniprot.org/uniprot/Q02788 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type VI collagen family.|||Collagen VI acts as a cell-binding protein.|||Highly expressed in adipose tissue, lung, adrenal glands and ovary. Lower levels in testis, tongue, skin, kidney, heart, intestine and spleen. No expression in skeletal muscle or liver.|||Membrane|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-4(VI) or alpha-5(VI) or alpha-6(VI). Interacts with CSPG4 (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Shisa9 ^@ http://purl.uniprot.org/uniprot/Q9CZN4 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shisa family. SHISA9 subfamily.|||Brain-specific. Mainly expressed in neurons, including in hippocampus, cerebral cortex, striatum, thalamus, olfactory bulb and cerebellum. Expressed in most brain structures during embryonic and postnatal development.|||Component of some AMPA receptors (ionotropic glutamate receptors) complex, at least composed of some AMPA receptor (GRIA1, GRIA2 and/or GRIA3), CACNG2 and SHISA9, as well as low level of DLG4.|||Induces an increase in the paired-pulse ratio of AMPA currents in lateral and medial perforant path-granule cell synapses.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Produced by aberrant splicing sites.|||Regulator of short-term neuronal synaptic plasticity in the dentate gyrus. Associates with AMPA receptors (ionotropic glutamate receptors) in synaptic spines and promotes AMPA receptor desensitization at excitatory synapses.|||Synapse|||The extracellular domain contains a pattern of cysteine similar to the snail conotoxin Con-ikot-ikot (AC P0CB20), a toxin known to disrupt AMPA receptors (ionotropic glutamate receptor) desensitization.|||dendritic spine membrane http://togogenome.org/gene/10090:Zfp512 ^@ http://purl.uniprot.org/uniprot/Q69Z99 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Scgb1c1 ^@ http://purl.uniprot.org/uniprot/G5E8B5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Mindy3 ^@ http://purl.uniprot.org/uniprot/Q9CV28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MINDY deubiquitinase family. FAM188 subfamily.|||Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.|||Interacts with COPS5.|||Nucleus http://togogenome.org/gene/10090:Nek7 ^@ http://purl.uniprot.org/uniprot/Q3TN15|||http://purl.uniprot.org/uniprot/Q9ES74 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-97.|||Cytoplasm|||Displays an autoinhibited conformation: Tyr-97 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9.|||Monomer (By similarity). Interacts with NEK9; interaction takes place during mitosis; it relieves NEK7 autoinhibition and prevents interaction with NLRP3 (By similarity). Interacts with ANKS3; this interaction alters the subcellular distribution of NEK7 by preventing its nuclear translocation (PubMed:26188091). Interacts (via N-terminus) with NLRP3 (via LRR repeat domain); the interaction is required for the formation of the complex NLRP3:PYCARD, oligomerization of PYCARD and activation of CASP1 (PubMed:26553871, PubMed:26814970, PubMed:26642356).|||Mutant mice are viable but are born at sub-Mendelian ratios. They further suffer from severe growth retardation, infertility, abnormal gait and slight paralysis of the limbs. In an experimental autoimmune encephalitis (EAE) model, mutant mice exhibited reduced disease severity relative to wild-type mice, as well as reduced recruitment of lymphocytes, monocytes/microglia, and NK cells to the spinal cord.|||Nucleus|||Phosphorylation at Ser-195 required for its activation.|||Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:20473324). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:20473324). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (By similarity). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:26814970). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26553871, PubMed:26642356, PubMed:26814970). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:26814970).|||The NTE (N-terminal extension) motif is a structural component of the catalytic domain and thus contributes to activity.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Or10d1c ^@ http://purl.uniprot.org/uniprot/Q9EQ87 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppp4r3a ^@ http://purl.uniprot.org/uniprot/E9Q481|||http://purl.uniprot.org/uniprot/Q6P2K6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMEK family.|||Cytoplasm|||Nucleus|||Regulatory subunit of serine/threonine-protein phosphatase 4. May regulate the activity of PPP4C at centrosomal microtubule organizing centers. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on 'Ser-140' (gamma-H2AX) generated during DNA replication and required for DNA DSB repair (By similarity).|||Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complex PPP4C-PPP4R2-PPP4R3A. Interacts with PPP4C; the interaction requires PPP4R2 (By similarity).|||centrosome http://togogenome.org/gene/10090:Dock2 ^@ http://purl.uniprot.org/uniprot/Q6A0A3|||http://purl.uniprot.org/uniprot/Q8C3J5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DOCK family.|||Endomembrane system|||Homodimer (Probable). Interacts with RAC1 and RAC2. Interacts with CRKL and VAV. Interacts with CD3Z (By similarity).|||Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2.|||Specifically expressed in hematopoietic cells.|||The DOCKER domain probably mediates the GEF activity.|||cytoskeleton http://togogenome.org/gene/10090:Zic1 ^@ http://purl.uniprot.org/uniprot/P46684 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator. Involved in neurogenesis. Plays important roles in the early stage of organogenesis of the CNS, as well as during dorsal spinal cord development and maturation of the cerebellum. Involved in the spatial distribution of mossy fiber (MF) neurons within the pontine gray nucleus (PGN). Plays a role in the regulation of MF axon pathway choice. Promotes MF migration towards ipsilaterally-located cerebellar territories. May have a role in shear flow mechanotransduction in osteocytes. Retains nuclear GLI1 and GLI3 in the cytoplasm. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'.|||Belongs to the GLI C2H2-type zinc-finger protein family.|||Cytoplasm|||Expressed in osteoblasts (at protein level). Expressed in the CNS. A high level expression is seen in the cerebellum, while a low level expression is seen in the olfactory bulb, diencephalon, and brainstem. Expressed in lumbar spine and iliac crest.|||Expressed in progenitor cells in the dorsal third of the ventricular zone at 12.5 dpc. Expressed in newly emerging pontine gray nucleus (PGN) precursor cells of the extramural migratory stream (ems) between 12.5 and 14.5 dpc. Expressed in precerebellar mossy fiber (MF) neurons of the PGN (located either rostromedially or caudolaterally) persisted through at least P8 after birth (at protein level). In the early embryonic stage, it is expressed in the dorsal half of the neural tube and adjacent mesenchyme, and in the developing cerebellum it is expressed persistently in the granule cell lineage throughout the prenatal and postnatal periods.|||Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5). Interacts with GLI1; the interaction enhances transcription activation. Interacts with GLI2. Interacts with GLI3; the interaction enhances transcription activation.|||Mice show a cell mass decrease of the spinal dorsal horn, hypoplasia and abnormal foliation patterns in the cerebellum.|||Nucleus|||The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation. http://togogenome.org/gene/10090:Asprv1 ^@ http://purl.uniprot.org/uniprot/Q09PK2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By 12-O-tetradecanoylphorbol-13-acetate (TPA). No TPA-induced expression is seen in mice lacking Fos.|||Expression is first detected at embryonic day 15.5.|||Highly expressed in stratified epithelia in skin, tongue, esophagus, forestomach and vagina. Also expressed in trachea, urinary bladder and thymus. Undetectable in simple epithelia. Within the epidermis, expressed exclusively in the granular layer (at protein level). Levels are elevated in benign skin tumors but are down-regulated in squamous cell carcinomas.|||Homodimer.|||Membrane|||Mice display fine wrinkles on the lateral trunk which start to form 5 weeks after birth. There are no apparent epidermal differentiation defects.|||Protease responsible for filaggrin processing, essential for the maintenance of a proper epidermis organization.|||Undergoes autocleavage which is necessary for activation of the protein. http://togogenome.org/gene/10090:Numbl ^@ http://purl.uniprot.org/uniprot/O08919|||http://purl.uniprot.org/uniprot/Q3UH86 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in neural progenitor and neuron cells throughout the developing nervous system. Expressed in somites and throughout the neural tube from 8.5 dpc, onward.|||Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-terminal) with TRAF6 (via TRAF domains) (By similarity). Associates with EPS15 and NOTCH1.|||No visible phenotype. Mutants are viable and fertile. Mice lacking both Numb and Numbl genes die around 9.5 dpc, with severe defects in somite and vasculature formation, neuronal tube closure and axial turning. Conditional double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated in neural progenitor cells from 8.5 dpc (just before the onset of neurogenesis), display a loss of neural progenitor cells formation and an overexpression of neurons as neurogenesis progresses; cdKO mutants become necrotic at 12.5 dpc and die around this stage. Conditional double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated in neural progenitor cells from 10.5 dpc (just after the onset of neurogenesis), display a premature depletion of neural progenitor cells in the dorsal forebrain ventrical zone of the neocortex and in the hippocampal CA fields as neurogenesis progresses; cdKO mutants are viable and fertile, but showed a reduction in the thickness of the neocortex and the hippocampus and an enlargement of the lateral ventricles. Tamoxifen-inducible double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated postnatally in the subventricular zone (SVZ) neuroprogenitors and in ependymal cells, display a loss of SVZ neuroblasts and show a disorganized ependyma lacking both interdigitation junction between neighboring cells and increasing number of separated cells.|||Plays a role in the process of neurogenesis.|||Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF-kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and degradation of TRAF6 in cortical neurons.|||Preferentially expressed in the nervous system. In the developing neocortex, expressed in postmitotic neurons in the cortical plate but not in progenitors within the ventricular zone.|||The PTB domain is necessary for the inhibition of MAP3K7IP2-mediated activation of NF-kappa-B. http://togogenome.org/gene/10090:Nipsnap1 ^@ http://purl.uniprot.org/uniprot/O55125|||http://purl.uniprot.org/uniprot/Q5SVF7 ^@ Similarity ^@ Belongs to the NipSnap family. http://togogenome.org/gene/10090:Cdca4 ^@ http://purl.uniprot.org/uniprot/Q9CWM2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Developmentally regulated. Preferential expression in both fetal and adult hematopoietic progenitors and mature blood cells during embryonic and adult hematopoiesis.|||Expressed preferentially in hematopoietic progenitors and mature blood cells. Expressed at low levels in the heart, lung, spleen, and thymus and at a higher level in muscle.|||May participate in the regulation of cell proliferation through the E2F/RB pathway (By similarity). May be involved in molecular regulation of hematopoietic stem cells and progenitor cell lineage commitment and differentiation.|||Nucleus http://togogenome.org/gene/10090:Ddx49 ^@ http://purl.uniprot.org/uniprot/Q4FZF3 ^@ Similarity ^@ Belongs to the DEAD box helicase family. DDX49/DBP8 subfamily. http://togogenome.org/gene/10090:Otub1 ^@ http://purl.uniprot.org/uniprot/Q7TQI3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C65 family.|||By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1.|||Cytoplasm|||Hydrolase that can specifically remove compared to 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation (By similarity). Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen (PubMed:14661020). Acts via its interaction with RNF128/GRAIL (PubMed:14661020). Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128 (PubMed:14661020). Deubiquitinates estrogen receptor alpha (ESR1) (By similarity). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains (By similarity). Not able to cleave di-ubiquitin (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin (By similarity).|||Interacts with RNF128. Forms a ternary complex with RNF128 and USP8. Interacts with FUS and RACK1. Interacts with UBE2D1/UBCH5A, UBE2W/UBC16 and UBE2N/UBC13.|||Phosphorylation at Tyr-26 by SRC and SRMS promotes deubiquitination of RPTOR via a non-catalytic process.|||Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain. Acts as a regulator of mTORC1 and mTORC2 complexes. When phosphorylated at Tyr-26, acts as an activator of the mTORC1 complex by mediating deubiquitination of RPTOR via a non-catalytic process: acts by binding and inhibiting the activity of the ubiquitin-conjugating enzyme E2 (UBE2D1/UBCH5A, UBE2W/UBC16 and UBE2N/UBC13), thereby preventing ubiquitination of RPTOR. Can also act as an inhibitor of the mTORC1 and mTORC2 complexes in response to amino acids by mediating non-catalytic deubiquitination of DEPTOR. http://togogenome.org/gene/10090:Telo2 ^@ http://purl.uniprot.org/uniprot/Q9DC40 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TEL2 family.|||Component of the TTT complex composed of TELO2, TTI1 and TTI2. Interacts with ATM, ATR, MTOR, PRKDC, RUVBL2, TTI1, TTI2, SMG1 and TRRAP. Component of the mTORC1 and mTORC2 complexes. Interacts (phosphorylated form) with PIH1D1 (PubMed:24794838). Interaction with PIH1D1 mediates interaction of TELO2 with the R2TP complex composed of RUVBL1, RUVBL2, PIH1D1, and RPAP3 (By similarity).|||Cytoplasm|||Hydroxylation by PHD3 is required for a proper interaction with ATR, and activation of the ATR/CHK1/p53 pathway following DNA damage.|||Membrane|||Nucleus|||Phosphorylated at Ser-486 by CK2 following growth factor deprivation, leading to its subsequent ubiquitination by the SCF(FBXO9) complex. Phosphorylation by CK2 only takes place when TELO2 is bound to mTORC1, not mTORC2; leading to selective ubiquitination of mTORC1-associated protein (By similarity).|||Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. May be involved in telomere length regulation (By similarity).|||Ubiquitinated by the SCF(FBXO9) complex following phosphorylation by CK2 in response to growth factor deprivation, leading to its degradation by the proteasome. Only mTORC1-associated protein is ubiquitinated and degraded, leading to selective inactivation of mTORC1 to restrain cell growth and protein translation, while mTORC2 is activated due to the relief of feedback inhibition by mTORC1 (By similarity).|||telomere http://togogenome.org/gene/10090:Slc37a3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J133|||http://purl.uniprot.org/uniprot/Q3TIT8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.|||Endoplasmic reticulum membrane|||Glycosylated.|||Interacts with ATRAID; the interaction is direct and both proteins are mutually dependent for their stability.|||Lysosome membrane|||Membrane|||Unlike the other SLC37 members, lacks glucose-6-phosphate antiporter activity (By similarity). In osteoclasts, forms a transporter complex with ATRAID for nitrogen-containing-bisphophonates (N-BPs) required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol (PubMed:29745899). http://togogenome.org/gene/10090:Kcnh4 ^@ http://purl.uniprot.org/uniprot/A2A5F7 ^@ Subcellular Location Annotation|||Subunit ^@ Membrane|||The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits. http://togogenome.org/gene/10090:Rpl10l ^@ http://purl.uniprot.org/uniprot/P86048 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the universal ribosomal protein uL16 family.|||Component of a male germ cell-specific 60S large ribosomal subunit (LSU), which contains RPL10L and RPL39L, instead of RPL10 and RPL39 paralogs (PubMed:28502657, PubMed:36517592). The composition of the rest of the complex is similar to classical ribosomes (PubMed:36517592).|||Cytoplasm|||Spermatogenic failure and male infertility (PubMed:28502657). Spermatocytes show defects in the transition from prophase to metaphase of meiosis I due to impaired ribosome biogenesis in late prophase spermatocytes (PubMed:28502657).|||Testis-specific component of the ribosome, which is required for the transition from prophase to metaphase in male meiosis I (PubMed:28502657). Compensates for the inactivated X-linked RPL10 paralog during spermatogenesis (PubMed:28502657). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:28502657). The male germ cell-specific ribosome displays a ribosomal polypeptide exit tunnel of distinct size and charge states compared with the classical ribosome (PubMed:36517592). It is responsible for regulating the biosynthesis and folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm (PubMed:36517592).|||Testis-specific. http://togogenome.org/gene/10090:Tmeff2 ^@ http://purl.uniprot.org/uniprot/Q9QYM9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A soluble form (TMEFF2-ECD) is produced by proteolytic shedding. This shedding can be induced by phorbol ester or pro-inflammatory cytokines such as TNFalpha, and is mediated by a metalloproteinase ADAM (By similarity).|||Belongs to the tomoregulin family.|||First detected at 11 dpc, reaches a maximum at 15 dpc, and remains constant through 17 dpc.|||May be a survival factor for hippocampal and mesencephalic neurons. The shedded form may up-regulate cell proliferation (By similarity).|||Membrane|||O-glycosylated; contains chondroitin sulfate glycosaminoglycans.|||Widely expressed in the brain. In the olfactory bulb expressed in mitral cell, granule, and glomerular layers. In the hippocampus expressed in hippocampal cornu ammonis, pyramidal layer, dentate gyrus, and substantia nigra pars compacta. http://togogenome.org/gene/10090:Xpa ^@ http://purl.uniprot.org/uniprot/Q64267 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the XPA family.|||Deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. They develop stronger longer-lasting acute inflammation, they show a more severe UV-induced damage of keratinocytes and Langerhans cells as well as the enhancement of local and systemic immunosuppression. PGE2 and COX2 expression is greatly increased after UVB irradiation, this causes the enhancement of inflammation and immunosuppression. Natural killer cell activity is also significantly decreased (PubMed:11764287). Knockout in a Polr2a 'R-1268' knockin mouse leads to growth retardation, skeletal abnormalities, cataracts, progressive motor neuron degeneration and death at 5-6 months (PubMed:32142649).|||Exhibits a circadian pattern with zenith at around 5 pm and nadir at around 5 am in liver but not in testis, this oscillation is dependent on the circadian clock and on HERC2 regulation.|||Interacts with GPN1. Interacts with RPA1 and RPA2; the interaction is direct and associates XPA with the RPA complex. Interacts (via N-terminus) with CEP164 upon UV irradiation. Interacts with HERC2 (By similarity).|||Involved in DNA excision repair. Initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. Required for UV-induced CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation (By similarity).|||Nucleus|||Plays an essential role in the repair of cisplatin induced damage by nucleotide excision repair. Cisplatin is one of the most commnly used anticancer drugs.|||Ubiquitinated by HERC2 leading to degradation by the proteasome. http://togogenome.org/gene/10090:Mc1r ^@ http://purl.uniprot.org/uniprot/A0A0B6VTJ4|||http://purl.uniprot.org/uniprot/Q01727 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production. Interacts with OPN3; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes.|||Membrane|||Receptor for MSH (alpha, beta and gamma) and ACTH (PubMed:1325670). The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:1325670). Mediates melanogenesis, the production of eumelanin (black/brown) and phaeomelanin (red/yellow), via regulation of cAMP signaling in melanocytes (By similarity).|||Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. http://togogenome.org/gene/10090:Cdk5rap3 ^@ http://purl.uniprot.org/uniprot/Q99LM2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDK5RAP3 family.|||Cleaved by caspases early during apoptosis, the resulting peptides may play a role in rupture of the nuclear envelope.|||Cytoplasm|||Interacts with CDK5R1; competes with CDK5RAP1 and CDK5RAP2 (By similarity). Interacts with RELA (By similarity). Interacts with CHEK1; may negatively regulate CHEK1 and thereby stimulate entry into mitosis (By similarity). Interacts with CDKN2A/ARF and MDM2; forms a ternary complex involved in regulation of p53/TP53 (By similarity). Interacts with UFL1; the interaction is direct (PubMed:21494687, PubMed:30635284). Interaction with UFL1 anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition (By similarity). Interacts with DDRGK1 (By similarity). Interacts with MAPK14 (By similarity). Interacts with CCNB1 (By similarity). Interacts with TUBG1; may regulate CDK5RAP3 in mitotic G2/M transition checkpoint (By similarity).|||May be phosphorylated by CDK5.|||May be ufmylated.|||Nucleus|||Predominantly expressed in hepatocytes during liver development.|||Prenatal lethality, probably caused by severe liver hypoplasia (PubMed:30635284). 16.5 dpc mutant embryos also show defects in definitive erythropoiesis (PubMed:30635284). Conditional knockout mice lacking Cdk5rap3 in hepatocytes causes lethality after weaning -specific Cdk5rap3 display liver hypoplasia and die after weaning (PubMed:30635284).|||Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, in response to endoplasmic reticulum stress (PubMed:30635284). Negatively regulates NF-kappa-B-mediated gene transcription through the control of RELA phosphorylation (By similarity). Probable tumor suppressor initially identified as a CDK5R1 interactor controlling cell proliferation (By similarity). Also regulates mitotic G2/M transition checkpoint and mitotic G2 DNA damage checkpoint (By similarity). Through its interaction with CDKN2A/ARF and MDM2 may induce MDM2-dependent p53/TP53 ubiquitination, stabilization and activation in the nucleus, thereby promoting G1 cell cycle arrest and inhibition of cell proliferation (By similarity). May also play a role in the rupture of the nuclear envelope during apoptosis (By similarity). May regulate MAPK14 activity by regulating its dephosphorylation by PPM1D/WIP1 (By similarity). Required for liver development (PubMed:30635284).|||Ubiquitinated. Probably triggers proteasomal degradation and is negatively regulated by UFL1.|||Widely expressed with higher expression in secretory tissues.|||centrosome http://togogenome.org/gene/10090:Slc1a2 ^@ http://purl.uniprot.org/uniprot/A2APL7|||http://purl.uniprot.org/uniprot/A2APL8|||http://purl.uniprot.org/uniprot/P43006|||http://purl.uniprot.org/uniprot/Q3UYK6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.|||Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A2 subfamily.|||Cell membrane|||Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.|||Detected in brain (PubMed:9180080). Detected in embryonic forebrain, especially in globus pallidus, perirhinal cortex, lateral hypothalamus, hippocampus, and on fimbria and axonal pathways connecting the neocortex, basal ganglia and thalamus (at protein level) (PubMed:16880397). Isoform GLT1 is expressed in the brain (PubMed:7698742, PubMed:7557442, PubMed:9373176, PubMed:9180080). Isoforms GLT-1A and GLT-1B are expressed in the liver (PubMed:9373176).|||Glycosylated.|||Homotrimer (By similarity). Interacts with AJUBA (By similarity).|||Membrane|||No visible phenotype at birth (PubMed:9180080, PubMed:16880397). Mice are born at the expected Mendelian rate, but gain weight more slowly, especially after the first 30 days after birth (PubMed:9180080). Only half of them are still alive 60 days after birth (PubMed:9180080). Death is due to spontaneous epileptic seizures (PubMed:9180080). Besides, mutant mice display neuronal degeneration in the hippocampus CA1 field, probably due to impaired glutamate removal from the synaptic cleft (PubMed:9180080). Glutamate uptake by synaptosomes from mutant mouse brain cortex is reduced by 94% (PubMed:9180080). Mice deficient in both Slc1a2 and Slc1a3 die at about 17 dpc; they display defects in the brain structure that affects the brain cortex, hippocampus and olfactory bulb, due to impaired radial migration of neurons into the cortical plate and disorganization of the radial glial cell arrangement (PubMed:16880397).|||Palmitoylation at Cys-38 is not required for correct subcellular localization, but is important for glutamate uptake activity.|||Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7698742, PubMed:7557442, PubMed:9373176). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (By similarity). Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (PubMed:9180080). http://togogenome.org/gene/10090:Luc7l ^@ http://purl.uniprot.org/uniprot/A0A0R4J047|||http://purl.uniprot.org/uniprot/Q3TV90|||http://purl.uniprot.org/uniprot/Q9CYI4 ^@ Function|||Similarity ^@ Belongs to the Luc7 family.|||May bind to RNA via its Arg/Ser-rich domain. http://togogenome.org/gene/10090:L3mbtl1 ^@ http://purl.uniprot.org/uniprot/A2A5N8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in brain, testis, eyes, and ES cells.|||Homodimer. Interacts with RB1/RB (when monomethylated at 'Lys-860'). Interacts with p53/TP53 (when monomethylated at 'Lys-382'). Interacts with CBX3, ETV6, KMT5A and VCP/p97 (By similarity).|||No visible phenotype. Mice develop and reproduc normally. Mice were followed for more than 2 years, without any alteration in normal lifespan or survival with or without sublethal irradiation.|||Nucleus|||Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/H1-4 at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis (By similarity).|||The MBT repeat 2 specifically recognizes and binds monomethylated and dimethylated proteins. In contrast, it does not bind trimethylated proteins. The MBT repeat 1 does not bind methylated peptides but inserts a proline ring in a Pro-Ser-Ser/Thr sequence context (By similarity).|||Ubiquitinated in a VCP/p97-dependent way following DNA damage, leading to its removal from DNA damage sites, promoting accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited to DNA damage sites. http://togogenome.org/gene/10090:Tnfaip8l1 ^@ http://purl.uniprot.org/uniprot/Q8K288 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of mTOR activity.|||Belongs to the TNFAIP8 family.|||Cytoplasm|||Detected in wide variety tissues, such as neurons in brain, hepatocytes, germ cells of female and male reproductive organs, muscular tissues and variety types of cells of the epithelial origin (at protein level).|||Interacts with FBXW5; TNFAIP8L1 competes with TSC2 to bind FBXW5 increasing TSC2 stability by preventing its ubiquitination.|||Up-regulated by oxidative stress and by 6-hydroxydopamine (6-OHDA) in dopaminergic neurons. http://togogenome.org/gene/10090:Rps21 ^@ http://purl.uniprot.org/uniprot/Q9CQR2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS21 family.|||Component of the 40S small ribosomal subunit.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm|||Rough endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Chil3 ^@ http://purl.uniprot.org/uniprot/O35744 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.|||Cytoplasm|||Cytoplasmic granule|||Expressed in peritoneal cavity macrophages and in peritoneal and bone marrow-derived neutrophils. Abundantly expressed in bone marrow, with moderate levels detected in gastric antrum, spleen and in alveolar macrophages in lung. Not detected in brain, heart, liver, kidney, stomach, intestine, skeletal muscle, ovary, testis, thymus and lymph nodes (at protein level). Detected at low levels in bone marrow, spleen, thymus and lung. Barely detectable in intestine, kidney and coecum.|||In yolk sac, first detected at low levels at 8.5 dpc, with significant expression detected at 10.5 dpc in myeloid precursor cells. In liver, expressed from 16.5 dpc to P7.5 with highest levels detected from 18.5 dpc to P0.5. In spleen, first detected at 16.5 dpc, with peak levels detected at 18.5 dpc and P0.5 and expression persisting through the spleen maturation to the adult stage. In bone marrow, high expression levels detected from 16.5 dpc until adulthood. In lung, first detected around the time of birth, with levels increasing significantly from P14.5 towards adulthood.|||Lectin that binds saccharides with a free amino group, such as glucosamine or galactosamine. Binding to oligomeric saccharides is much stronger than binding to mono- or disaccharides. Also binds chitin and heparin. Has weak hexosaminidase activity but no chitinase activity. Has chemotactic activity for T-lymphocytes, bone marrow cells and eosinophils. May play a role in inflammation and allergy.|||Nucleus envelope|||Rough endoplasmic reticulum lumen|||Secreted|||Up-regulated in response to IL3 and IL4, during the inflammatory response and upon parasitic infection. http://togogenome.org/gene/10090:Dram1 ^@ http://purl.uniprot.org/uniprot/Q9DC58 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DRAM/TMEM150 family.|||Lysosomal modulator of autophagy that plays a central role in p53/TP53-mediated apoptosis. Not involved in p73/TP73-mediated autophagy (By similarity).|||Lysosome membrane http://togogenome.org/gene/10090:Fcgr2b ^@ http://purl.uniprot.org/uniprot/P08101 ^@ Domain|||Function|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Another tyrosine-containing sequence, more C-terminal, accounts for the ability of isoform IIB2 to trigger the phagocytosis of particulate immuno complexes.|||Glycosylated.|||Interacts with FGR (By similarity). Interacts with LYN.|||Ly-17 alloantigenic system involves residues 116 and 161. Ly-17.1 mice are Pro-116 and Glu-161; Ly-17.2 mice are Leu-116 and Leu-161. These polymorphisms do not affect IgG binding.|||Receptor for the Fc region of complexed immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of antigen-antibody complexes from the circulation and modulation of antibody production by B-cells. Isoform IIB1 and isoform IIB1' form caps but fail to mediate endocytosis or phagocytosis. Isoform IIB2 can mediate the endocytosis of soluble immune complexes via clathrin-coated pits. Isoform IIB1 and isoform IIB2 can down-regulate B-cell, T-cell, and mast cell activation when coaggregated to B-cell receptors for AG (BCR), T-cell receptors for AG (TCR), and Fc receptors, respectively.|||Secreted|||When coaggregated to BCR, isoform IIB1 and isoform IIB1' become tyrosine phosphorylated and bind to the SH2 domains of the protein tyrosine phosphatase PTPC1. Phosphorylated by SRC-type Tyr-kinases such as LYN, BLK, FYN and SYK (By similarity).|||Widely expressed by cells of hemopoietic origin. The isoforms are differentially expressed. Isoform IIB1 is preferentially expressed by cells of the lymphoid lineage, isoform IIB2 by cells of the myeloid lineage, and isoform IIB3 is released by macrophages and is present in the serum. Isoform IIB1' is expressed in myeloid and lymphoid cell lines, in normal spleen cells, and in resting or LPS-activated B-cells but is not detected in mesenteric lymph node cells.|||cytoskeleton http://togogenome.org/gene/10090:Ankrd33 ^@ http://purl.uniprot.org/uniprot/Q8BXP5 ^@ Developmental Stage|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a transcriptional repressor for CRX-activated photoreceptor gene regulation.|||Expression is up-regulated by the CRX transcription factor.|||Isoform 1: Expressed predominantly in the retina. Isoform 2: Expressed in the pineal gland.|||Nucleus|||Predominantly expressed in developing and mature photoreceptors (at protein level).|||Unlikely isoform. Aberrant splice sites.|||cytosol http://togogenome.org/gene/10090:Nectin3 ^@ http://purl.uniprot.org/uniprot/Q9JLB9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nectin family.|||Cell membrane|||Cis- and trans-homodimer. Can form trans-heterodimers with NECTIN1, NECTIN2, PVR, IGSF4B/Necl-1 and with IGSF4. Interaction between NECTIN1 and NECTIN3 on the pre- and postsynaptic sites, respectively, initiates the formation of puncta adherentia junctions between axons and dendrites. Interacts (via Cytoplasmic domain) with AFDN, providing a connection with the actin cytoskeleton. Binds with low affinity to TIGIT.|||Mice show an ocular phenotype, microphthalmia, accompanied by a separation of the contact between the pigment and non-pigment cell layers of the ciliary epithelia. Male mice exhibits infertility, suggesting a role in spermatogenesis. In the hippocampus, the formation and the number of adherens junctions at the synapses is impaired, and the trajectory of mossy fiber is abnormal.|||Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectins-like or other nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions. Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body.|||Postsynaptic cell membrane|||Ubiquitous with high expression in testes. Localized in spermatids at Sertoli-spermatid junctions. Expressed in ovarian granulosa cells, but only faintly expressed after ovulation. http://togogenome.org/gene/10090:Cldn12 ^@ http://purl.uniprot.org/uniprot/Q9ET43 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the claudin family.|||Cell membrane|||Interacts with OCLN.|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Gm5157 ^@ http://purl.uniprot.org/uniprot/A0A087WRH8 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Sox18 ^@ http://purl.uniprot.org/uniprot/P43680 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds target DNA via the HMG box domain.|||Defects in this protein are the cause of the ragged, ragged-like and opossum phenotypes (PubMed:10742113, PubMed:12748961, PubMed:18931657, PubMed:19429912). In all these, missense mutations give rise to a truncated protein that retains DNA-binding ability, but lacks regions required for transcription activation (PubMed:10742113, PubMed:12748961). Homozygous ragged and ragged-like mice are almost completely naked, display prenatal edema and frequently die in utero or shortly after birth. Heterozygous ragged and ragged-like mice are mostly viable, but have a thin, ragged coat (PubMed:12748961). Homozygous opossum mice display no visible phenotype up to 11.5 dpc (PubMed:19429912). From 12.5 dpc onwards, mutant embryos display enlarged surface microvasculature and severe subcutaneaous edema, followed by vascular rupture and hemorrhage beginning at 13.5 dpc (PubMed:18931657, PubMed:19429912). All die shortly after 14.5 dpc (PubMed:12748961, PubMed:18931657, PubMed:19429912). Heterozygous opossum mice are almost completely naked, display prenatal edema and frequently die in utero or shortly after birth (PubMed:12748961). Heterozygous opossum mice display defects in development and patterning of the lymph vessels (PubMed:18931657).|||Deletion of the DNA-binding and the C-terminal transcription activation domains causes no visible phenotype, excepting slightly darker coat pigmentation and a decreased proportion of auchene and zigzag hairs (PubMed:11094083). The mild phenotype is due to functional redundancy with other Sox genes (PubMed:11094083, PubMed:16895970). The phenotype apparently depends on the genetic context: backcrossing the mutant into a pure C57BL/6 background leads to defective lymphangiogenesis and the same embryonic lethality as observed for opossum mutants (PubMed:18931657).|||Detected at 7.5 and 8.0 dpc in the allantois and blood islands of the yolk sac, and in cells fated to become the endocardium. At 8.5 dpc, detected in the allantois and the nascent vasculature of the yolk sac, the paired dorsal aortae and heart (PubMed:10742113). At 9.5 to 11.0 dpc, detected in endothelial cells of the paired dorsal aortae, in intersomitic vessels and in a network of smaller vessels in head and trunc mesenchyme, and in endothelial cells lining the dorsolateral sector of the cardinal vein (PubMed:10742113, PubMed:18931657). At 10.5 dpc, detected inprecursors of the lymphatic vasculature (PubMed:18931657). At 12.5 dpc, detected in branching vessels and in nascent vibrissae follicles. Detected in vibrissae follicles and pelage follicles at 14.0 dpc (PubMed:10742113). Detected in primary lymph sacs at 13.5 dpc, but is not detected in embryonic or adult lymph vessels (PubMed:18931657).|||Detected in adult lung, heart and skeletal muscles.|||Interacts (via C-terminus) with MEF2C (via MADS box).|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional activator that binds to the consensus sequence 5'-AACAAAG-3' in the promoter of target genes and plays an essential role in embryonic cardiovascular development and lymphangiogenesis (PubMed:7651823, PubMed:10742113, PubMed:12748961, PubMed:18931657, PubMed:19429912, PubMed:26939885). Activates transcription of PROX1 and other genes coding for lymphatic endothelial markers (PubMed:18931657, PubMed:26939885). Plays an essential role in triggering the differentiation of lymph vessels, but is not required for the maintenance of differentiated lymphatic endothelial cells (PubMed:18931657). Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX17 (PubMed:16895970). Interaction with MEF2C enhances transcriptional activation (PubMed:11554755). Besides, required for normal hair development (PubMed:11094083, PubMed:12748961). http://togogenome.org/gene/10090:Hmgn5 ^@ http://purl.uniprot.org/uniprot/Q9JL35 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 7.5 dpc, expression is detected in the ectoplacental cone but not in embryonic tissues. By 9.5 dpc and 12.5 dpc, strongly expressed in the giant trophoblast, spongiotrophoblast and decidual cells of the placenta (at protein level). At 9.5 dpc and 11.5 dpc, weakly expressed in the developing embryo.|||Belongs to the HMGN family.|||Expressed in liver, spleen, lung, heart, kidney, muscle and brain (at protein level). Widely expressed with highest levels in submaxillary gland, thymus, kidney and liver and lowest levels in brain, lung, pancreas and eye.|||Nucleus|||Preferentially binds to euchromatin and modulates cellular transcription by counteracting linker histone-mediated chromatin compaction.|||Specifically targeted by its C-terminus to nucleosomes in euchromatin. http://togogenome.org/gene/10090:Dpp4 ^@ http://purl.uniprot.org/uniprot/P28843|||http://purl.uniprot.org/uniprot/Q3TR43 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the peptidase S9B family. DPPIV subfamily.|||Cell junction|||Cell membrane|||Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.|||Inhibited by GPC3 and diprotin A.|||Membrane raft|||Monomer. Homodimer. Heterodimer with Seprase (FAP). Requires homodimerization for optimal dipeptidyl peptidase activity and T-cell costimulation. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Associates with collagen. Interacts with PTPRC; the interaction is enhanced in an interleukin-12-dependent manner in activated lymphocytes. Interacts (via extracellular domain) with ADA; does not inhibit its dipeptidyl peptidase activity. Interacts with CAV1 (via the N-terminus); the interaction is direct. Interacts (via cytoplasmic tail) with CARD11 (via PDZ domain); its homodimerization is necessary for interaction with CARD11. Interacts with IGF2R; the interaction is direct. Interacts with GPC3.|||N- and O-Glycosylated.|||Phosphorylated. Mannose 6-phosphate residues in the carbohydrate moiety are necessary for interaction with IGF2R in activated T-cells. Mannose 6-phosphorylation is induced during T-cell activation (By similarity).|||Secreted|||The soluble form (Dipeptidyl peptidase 4 soluble form also named SDPP) derives from the membrane form (Dipeptidyl peptidase 4 membrane form also named MDPP) by proteolytic processing.|||invadopodium membrane|||lamellipodium membrane http://togogenome.org/gene/10090:Adh7 ^@ http://purl.uniprot.org/uniprot/Q64437|||http://purl.uniprot.org/uniprot/Q9D748 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family.|||Belongs to the zinc-containing alcohol dehydrogenase family. Class-IV subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Catalyzes the NAD-dependent oxidation of all-trans-retinol, alcohol, aldehyde and omega-hydroxy fatty acids and their derivatives. Oxidizes preferentially all trans-retinol, all-trans-4-hydroxyretinol, 9-cis-retinol, 2-hexenol, and long chain omega-hydroxy fatty acids such as juniperic acid. In vitro can also catalyzes the NADH-dependent reduction of all-trans-retinal and aldehydes and their derivatives. Reduces preferentially all trans-retinal, all-trans-4-oxoretinal and hexanal. Catalyzes in the oxidative direction with higher efficiency. Therefore may participate in retinoid metabolism, fatty acid omega-oxidation, and elimination of cytotoxic aldehydes produced by lipid peroxidation.|||Cytoplasm|||High expression in the stomach mucosa. Lower expression in eye, thymus, skin and ovary. Very low expression in small intestine, liver and uterus.|||Homodimer.|||Retinol oxidation is inhibited by the detergent Tween 80. Ethanol inhibits both all-trans-retinol and 9-cis-retinol oxidation. 13-cis-retinol is an effective competitive inhibitor of the 9-cis-retinol oxidation. All-trans-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. 13-cis-retinoic acid is a powerful inhibitor of all-trans-retinol oxidation. Cimetidine competitively inhibited ethanol oxidation. http://togogenome.org/gene/10090:Coq9 ^@ http://purl.uniprot.org/uniprot/Q8K1Z0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COQ9 family.|||Encephalomyopathy due to a widespread coenzyme Q deficiency and accumulation of demethoxyubiquinone. Lethality between 3 and 6 months of age, due to neuronal death and demyelinization with severe vacuolization and astrogliosis in the brain.|||Homodimer. Interacts with COQ7.|||Lipid-binding protein involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:25339443). Binds a phospholipid of at least 10 carbons in each acyl group. May be required to present its bound-lipid to COQ7 (By similarity).|||Mitochondrion|||Structurally similar to the bacterial FadR protein (fatty acid metabolism regulator protein). http://togogenome.org/gene/10090:Ptpdc1 ^@ http://purl.uniprot.org/uniprot/Q6NZK8 ^@ Disruption Phenotype|||Function|||Similarity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class PTPDC1 subfamily.|||Elongated cilia.|||May play roles in cilia formation and/or maintenance. http://togogenome.org/gene/10090:Ube2dnl2 ^@ http://purl.uniprot.org/uniprot/A2AFH2 ^@ Similarity ^@ Belongs to the ubiquitin-conjugating enzyme family. http://togogenome.org/gene/10090:Wdr13 ^@ http://purl.uniprot.org/uniprot/Q91V09 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Plcb1 ^@ http://purl.uniprot.org/uniprot/Q9Z1B3 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors (PubMed:27653213). Regulates the function of the endothelial barrier (PubMed:27653213).|||Cytoplasm|||Interacts with DGKQ.|||Nucleus membrane|||Palmitoylated (PubMed:27653213). Palmitoylation at Cys-17 by ZDHHC21 regulates the signaling activity of PLCB1 and the function of the endothelial barrier (Probable). Palmitoylation by ZDHHC21 is stimulated by inflammation (PubMed:27653213).|||The receptor-mediated activation of PLC-beta-1 is mediated by two G-protein alpha subunits, alpha-Q and alpha-11. http://togogenome.org/gene/10090:Fig4 ^@ http://purl.uniprot.org/uniprot/Q91WF7 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14 (By similarity) (PubMed:19037259). VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities (By similarity).|||Defects in Fig4 are the cause of the pale tremor phenotype which is a multi-organ disorder with neuronal degeneration in the central nervous system, peripheral neuronopathy and diluted pigmentation. At postnatal day three (P3), affected homozygotes have diluted pigmentation and reduced size. Intentional tremor develops during the second week after birth, and abnormal limb postures are evident by the third week. There is impaired motor coordination, muscle weakness and 'swimming' gait. There is progressive loss of mobility, reduction in body weight and juvenile lethality.|||Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the dephosphorylation of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) to form phosphatidylinositol 3-phosphate. Has serine-protein phosphatase activity acting on PIKfyve to stimulate its lipid kinase activity, its catalytically activity being required for maximal PI(3,5)P2 production. In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide and although displaying preferences for PtdIns(3,5)P2, it is capable of hydrolyzing PtdIns(3,4,5)P3 and PtdIns(4,5)P2, at least in vitro.|||Endosome membrane|||The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide substrates in the order PtdIns(4,5)P2 > PtdIns(3,5)P2 > PtdIns(3,4,5)P3. Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.|||Wide-spread. http://togogenome.org/gene/10090:Rflnb ^@ http://purl.uniprot.org/uniprot/Q5SVD0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15.5 dpc, expressed in developing ribs and nucleus pulposus in intervertebral disks. At 18.5 dpc, expression is detected in proliferating and prehypertrophic chondrocytes.|||Belongs to the Refilin family.|||Detected in various tissues, with highest expression in lung, followed by spleen.|||Interacts with FLNA and FLNB.|||Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in the formation of cartilaginous skeletal elements.|||No visible phenotype; probably due to redundancy with RFLN. RFLNA and RFLNB double mutant mice exhibit severe skeletal malformations, as characterized by scoliosis, kyphosis, intervertebral disks defects, vertebral fusion in the spine and longitudinal bone growth retardation. Chondrocyte maturation is accelerated in double mutant mice.|||cytoskeleton http://togogenome.org/gene/10090:Prr15 ^@ http://purl.uniprot.org/uniprot/A2RT92|||http://purl.uniprot.org/uniprot/Q9D1T5 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the PRR15 family.|||Exhibits a cell type specific expression pattern only in the small and large intestine and in the testis. Along the intestinal tract expression is restricted to the non-proliferating epithelial cells surrounding the villi and no expression is found in the intestinal crypts, where proliferation occurs. In the testis, it is detected only in post-mitotic secondary spermatocytes.|||Expressed in specific structures of the developing head, namely the brain, inner and middle ear, olfactory epithelium, vomeronasal organ, nasopharynx, oropharynx, papillae of the tongue and oral cavity, pituitary gland and epiglottis.|||May have a role in proliferation and/or differentiation. http://togogenome.org/gene/10090:Gcc1 ^@ http://purl.uniprot.org/uniprot/Q9D4H2 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Cytoplasm|||Extended rod-like protein with coiled-coil domains.|||Golgi apparatus membrane|||Probably involved in maintaining Golgi structure. http://togogenome.org/gene/10090:Odam ^@ http://purl.uniprot.org/uniprot/A1E960 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ODAM family.|||Cytoplasm|||Highly expressed in tooth-associated epithelia. Predominantly expressed in mandible.|||Interacts (via C-terminus) with ARHGEF5.|||Nucleus|||O-glycosylated.|||Secreted|||Tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth. May be incorporated in the enamel matrix at the end of mineralization process. Involved in the induction of RHOA activity via interaction with ARHGEF and expression of downstream factors such as ROCK. Plays a role in attachment of the junctional epithelium to the tooth surface. http://togogenome.org/gene/10090:Tas2r138 ^@ http://purl.uniprot.org/uniprot/Q7TQA6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Low levels in tongue, stomach and duodenum.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Cga ^@ http://purl.uniprot.org/uniprot/A0A0F7RQH1|||http://purl.uniprot.org/uniprot/P01216 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycoprotein hormones subunit alpha family.|||Expressed in the ventral area of the anterior pituitary gland from 13.5 dpc onwards, expression remains at 18.5 dpc.|||Heterodimer. The active hormones thyrotropin, lutropin and follitropin are heterodimers composed of CGA, a common alpha chain described here and a unique beta chain which confers their biological specificity to the hormones: TSHB for thyrotropin, LHB for lutropin and FSHB for follitropin.|||PubMed:6177696 sequence was originally thought to originate from rat.|||Secreted|||Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH and follitropin/follicle stimulating hormone/FSH. These hormones bind specific receptors on target cells that in turn activate downstream signaling pathways. http://togogenome.org/gene/10090:Rin2 ^@ http://purl.uniprot.org/uniprot/F8WGD2|||http://purl.uniprot.org/uniprot/Q9D684 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RIN (Ras interaction/interference) family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||Homotetramer; probably composed of anti-parallel linkage of two parallel dimers. Interacts with Ras. Interacts with RAB5B, with a much higher affinity for GTP-bound activated RAB5B. Does not interact with other members of the Rab family (By similarity).|||Ras effector protein. May function as an upstream activator and/or downstream effector for RAB5B in endocytic pathway. May function as a guanine nucleotide exchange (GEF) of RAB5B, required for activating the RAB5 proteins by exchanging bound GDP for free GTP (By similarity). http://togogenome.org/gene/10090:Zbp1 ^@ http://purl.uniprot.org/uniprot/Q9QY24 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts (via RIP homotypic interaction motif) with murid herpesvirus protein RIR1 (via RIP homotypic interaction motif); leading to inhibition of ZBP1-dependent necroptosis.|||(Microbial infection) Interacts with vaccinia virus E3 protein; leading to inhibit ZBP1-dependent necroptosis.|||According to a report, mice lacking Zbp1 display reductions in respiratory epithelial damage and lung inflammation (PubMed:27917412). However, the virus persists and replicates in the infected cells leading to a delay in recovery from infection, but the animals are protected from mortality (PubMed:27917412). In contrast, another article reported increased mortality in knockout mice, probably caused by increased virus burden (PubMed:27746097). However, as this study did not assess the inflammatory response in the lungs, it is difficult to compare ZBP1 regulation of lung inflammation between these two studies (PubMed:27746097).|||Cytoplasm|||Expressed in lung, spleen and liver. Lower levels were seen in heart, kidney and testis. Expression is greatly up-regulated in tumor stromal cells and activated macrophages.|||Expression is activated by IRF1 (PubMed:29321274). Up-regulated following interferon treatment (PubMed:10564822, PubMed:29073079). By lipopolysaccharides (LPS) (PubMed:10564822).|||Homodimer (PubMed:18375758). Interacts (via RIP homotypic interaction motif) with RIPK3; leading to RIPK3 activation and necroptosis; interaction is enhanced by CASP6 (PubMed:19590578, PubMed:22423968, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:28607035, PubMed:32200799, PubMed:32298652). Interacts (via RIP homotypic interaction motif) with RIPK1 (PubMed:19590578, PubMed:23283962, PubMed:33397971). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287).|||Key innate sensor that recognizes and binds Z-RNA structures, which are produced by a number of viruses, such as herpesvirus, orthomyxovirus or flavivirus, and triggers different forms of cell death (PubMed:17618271, PubMed:18375758, PubMed:19590578, PubMed:23283962, PubMed:27746097, PubMed:27917412, PubMed:27819681, PubMed:28716805, PubMed:28607035, PubMed:30050136, PubMed:31358656, PubMed:32200799, PubMed:32296175, PubMed:30498077, PubMed:29073079). ZBP1 acts as an essential mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, by activating RIPK3, caspase-8 (CASP8), and the NLRP3 inflammasome (PubMed:27746097, PubMed:27917412, PubMed:28607035, PubMed:32200799, PubMed:32298652, PubMed:32350114, PubMed:32296175). Key activator of necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, via its ability to bind Z-RNA: once activated upon Z-RNA-binding, ZBP1 interacts and stimulates RIPK3 kinase, which phosphorylates and activates MLKL, triggering execution of programmed necrosis (PubMed:22423968, PubMed:27746097, PubMed:27819681, PubMed:27819682, PubMed:28716805, PubMed:32200799, PubMed:32350114, PubMed:32315377, PubMed:32296175). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: ZBP1 recognizes and binds Z-RNA structures that are produced in infected nuclei by orthomyxoviruses, such as the influenza A virus (IAV), leading to ZBP1 activation, RIPK3 stimulation and subsequent MLKL phosphorylation, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (PubMed:32200799, PubMed:32296175). ZBP1-dependent cell death in response to IAV infection promotes interleukin-1 alpha (IL1A) induction in an NLRP3-inflammasome-independent manner: IL1A expression is required for the optimal interleukin-1 beta (IL1B) production, and together, these cytokines promote infiltration of inflammatory neutrophils to the lung, leading to the formation of neutrophil extracellular traps (PubMed:31630209). In addition to its direct role in driving necroptosis via its ability to sense Z-RNAs, also involved in PANoptosis triggered in response to bacterial infection: component of the AIM2 PANoptosome complex, a multiprotein complex that triggers PANoptosis (PubMed:34471287). Also acts as the apical sensor of fungal infection responsible for activating PANoptosis (PubMed:33109609). Involved in CASP8-mediated cell death via its interaction with RIPK1 but independently of its ability to sense Z-RNAs (PubMed:33397971). In some cell types, also able to restrict viral replication by promoting cell death-independent responses (PubMed:30635240). In response to flavivirus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with RIPK3, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate (PubMed:30635240). Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed:30635240).|||Mice are resistant to necroptosis, characterized by a decrease in epithelial cell death and an increase in virus replication (PubMed:22423968, PubMed:27746097, PubMed:27917412). At a modestly lethal dose of influenza A virus (IAV), mice display significantly increased rates of mortality, probably caused by a failure to eliminate infected cells and limit virus spread in pulmonary tissue (PubMed:32200799). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Zbp1 (PubMed:27819681, PubMed:27819682). Skin inflammation observed in Ripk1(mRHIM) mutant mice is abrogated in Ripk1(mRHIM) mutant mice that also lack Zbp1 (PubMed:27819681).|||Nucleus|||Phosphorylated.|||The Z-binding domains recognize and bind left-handed double-stranded Z-RNA structures, but not A-RNA, the right-handed double-stranded RNAs that are structurally very different from Z-RNAs (PubMed:32200799). The second Z-binding domain (also named Zalpha2) acts as a molecular switch regulating pyroptosis, necroptosis and apoptosis (PANoptosis) (PubMed:32350114, PubMed:33109609). The second Z-binding domain is essential for sensing influenza A virus (IAV) Z-RNAs (PubMed:28607035, PubMed:28716805, PubMed:32350114).|||Ubiquitinated; polyubiquitinated following influenza A virus (IAV) infection.|||ZBP1-dependent necroptosis is normally inhibited by RIPK1: RIPK1 inhibits the ZBP1-induced activation of RIPK3 via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis. http://togogenome.org/gene/10090:Zftraf1 ^@ http://purl.uniprot.org/uniprot/P0DW87 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZFTRAF1 family.|||Cytoplasm|||Expressed in heart, brain, liver, testis and kidney.|||Interacts with LGALS3.|||perinuclear region http://togogenome.org/gene/10090:Lsm10 ^@ http://purl.uniprot.org/uniprot/Q8QZX5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to function in the U7 snRNP complex that is involved in histone 3'-end processing (By similarity). Increases U7 snRNA levels but not histone 3'-end pre-mRNA processing activity, when overexpressed (By similarity). Required for cell cycle progression from G1 to S phases (By similarity). Binds specifically to U7 snRNA (By similarity). Binds specifically to U7 snRNA (By similarity). Binds to the downstream cleavage product (DCP) of histone pre-mRNA.|||Belongs to the snRNP Sm proteins family.|||Component of the heptameric ring U7 snRNP complex, or U7 Sm protein core complex, at least composed of LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF, SNRPG and U7 snRNA. Formation of the U7 snRNP is an ATP-dependent process mediated by a specialized SMN complex containing at least the Sm protein core complex and additionally, the U7-specific LSM10 and LSM11 proteins. Interacts with CLNS1A and SMN (By similarity).|||Not methylated. Methylation is not necessary for interaction with SMN (By similarity).|||Nucleus http://togogenome.org/gene/10090:Zhx1 ^@ http://purl.uniprot.org/uniprot/P70121|||http://purl.uniprot.org/uniprot/Q5DTL2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. Increases DNMT3B-mediated repressive transcriptional activity when DNMT3B is tethered to DNA. May link molecule between DNMT3B and other co-repressor proteins (By similarity).|||Belongs to the ZHX family.|||By interleukin-2.|||Forms homodimers. Heterodimer (via HD1 domain) with ZHX2 (via HD1 domain). Also forms a heterodimer with ZHX3 which is a prerequisite for repressor activity. Interacts with ATF7IP and NFYA. Interacts (via homeobox domains) with DNMT3B (via PWWP domain) (By similarity).|||Nucleus|||Widely expressed with highest levels in brain. http://togogenome.org/gene/10090:Or5j3 ^@ http://purl.uniprot.org/uniprot/Q8VGR8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Aste1 ^@ http://purl.uniprot.org/uniprot/Q8BIR2 ^@ Function|||Similarity ^@ Belongs to the asteroid family.|||Possible role in EGF receptor signaling. http://togogenome.org/gene/10090:Notch2 ^@ http://purl.uniprot.org/uniprot/O35516 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOTCH family.|||Can be either O-glucosylated or O-xylosylated at Ser-613 by POGLUT1.|||Cell membrane|||Cytoplasm|||Expressed in the brain, liver, kidney, neuroepithelia, somites, optic vesicles and branchial arches, but not heart.|||Expressed in the embryonic ventricular zone, the postnatal ependymal cells, and the choroid plexus throughout embryonic and postnatal development.|||Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination (PubMed:10393120). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus (PubMed:10393120, PubMed:18710934). Affects the implementation of differentiation, proliferation and apoptotic programs (PubMed:10393120, PubMed:18710934). May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation (By similarity). In collaboration with RELA/p65 enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation (PubMed:18710934). Positively regulates self-renewal of liver cancer cells (By similarity).|||Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH2. Interacts with RELA/p65. Interacts with HIF1AN. Interacts (via ANK repeats) with TCIM, the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (By similarity). Interacts with CUL1, RBX1, SKP1 and FBXW7 that are SCF(FBXW7) E3 ubiquitin-protein ligase complex components. Interacts with MINAR1; this interaction increases MINAR1 stability and function (By similarity). Interacts with MDK; this interaction mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3 (By similarity). Interacts with MINAR2 (By similarity).|||Hydroxylated by HIF1AN.|||Nucleus|||Phosphorylated by GSK3. GSK3-mediated phosphorylation is necessary for NOTCH2 recognition by FBXW7, ubiquitination and degradation via the ubiquitin proteasome pathway.|||Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form (PubMed:11459941, PubMed:11518718). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC) (PubMed:11459941, PubMed:11518718). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (By similarity). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (PubMed:11459941, PubMed:11518718). http://togogenome.org/gene/10090:E2f6 ^@ http://purl.uniprot.org/uniprot/O54917|||http://purl.uniprot.org/uniprot/Q8VHT4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E2F/DP family.|||Forms heterodimers with DP family members TFDP1 or TFDP2. Component of the DRTF1/E2F transcription factor complex. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10.|||Inhibitor of E2F-dependent transcription (PubMed:9403682). Binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' (PubMed:9403682, PubMed:18667754). Has a preference for the 5'-TTTCCCGC-3' E2F recognition site (PubMed:9403682). E2F6 lacks the transcriptional activation and pocket protein binding domains (PubMed:9403682). Appears to regulate a subset of E2F-dependent genes whose products are required for entry into the cell cycle but not for normal cell cycle progression (By similarity). Represses expression of some meiosis-specific genes, including SLC25A31/ANT4 (PubMed:18667754). May silence expression via the recruitment of a chromatin remodeling complex containing histone H3-K9 methyltransferase activity. Overexpression delays the exit of cells from the S-phase (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm14525 ^@ http://purl.uniprot.org/uniprot/B1AZA0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Adh4 ^@ http://purl.uniprot.org/uniprot/Q9QYY9 ^@ Activity Regulation|||Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Class-II subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Catalyzes the NAD-dependent oxidation of either all-trans-retinol or 9-cis-retinol (PubMed:17279314). Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate (PubMed:16081420). Also catalyzes the reduction of benzoquinones (By similarity).|||Cytoplasm|||Dimer.|||Has a much lower NAD-retinol dehydrogenase activity compared to the human ortholog.|||Liver specific.|||Oxidation of 20-HETE is inhibited by low concentrations of N-heptylformamide (PubMed:16081420). Oxidation of 20-HETE is a decreased by 55-65% by either all-trans-retinol or all-trans-retinoic acid (PubMed:16081420). Strongly inhibited by omega-hydroxy fatty acids (PubMed:10514444). http://togogenome.org/gene/10090:Gnai3 ^@ http://purl.uniprot.org/uniprot/Q9DC51 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||Cell membrane|||Cytoplasm|||Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha subunit contains the guanine nucleotide binding site. GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins (By similarity). Forms a complex with CCDC88A/GIV and EGFR which leads to enhanced EGFR signaling and triggering of cell migration; ligand stimulation is required for recruitment of GNAI3 to the complex (By similarity). Interacts (inactive GDP-bound form) with CCDC88A/GIV (via GBA motif); the interaction leads to activation of GNAI3 (By similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of GNAI3 (By similarity). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif) and NUCB2 (via GBA motif); the interaction leads to activation of GNAI3 (By similarity). Interacts (inactive GDP-bound form) with PLCD4 (via GBA motif); the interaction leads to activation of GNAI3 (By similarity). Interacts with INSR; the interaction is probably mediated by CCDC88A/GIV (By similarity). Interacts with GPSM1 (PubMed:16009138). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains). Does not interact with RGS2. Interacts with RGS8 and RGS10; this strongly enhances the intrinsic GTPase activity. Interacts with RGS16; this strongly enhances the intrinsic GTPase activity (By similarity). Interacts with RGS12 (By similarity). Interacts (via active GTP- or inactive GDP-bound form) with RGS14 (By similarity).|||Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins. Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels. Stimulates the activity of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.|||centrosome http://togogenome.org/gene/10090:Slu7 ^@ http://purl.uniprot.org/uniprot/Q8BHJ9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SLU7 family.|||Component of pre-catalytic, catalytic and post-catalytic spliceosomes. Associates with the spliceosome prior to recognition of the 3'-splice site for step II, probably during catalysis of step I.|||Cytoplasm|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the spliceosome. Participates in the second catalytic step of pre-mRNA splicing, when the free hydroxyl group of exon I attacks the 3'-splice site to generate spliced mRNA and the excised lariat intron. Required for holding exon 1 properly in the spliceosome and for correct AG identification when more than one possible AG exists in 3'-splicing site region. May be involved in the activation of proximal AG. Probably also involved in alternative splicing regulation.|||The CCHC-type zinc finger is required to retain the protein within the nucleus and prevent its shuttle back to the cytoplasm via the CRM1 pathway. http://togogenome.org/gene/10090:Prss37 ^@ http://purl.uniprot.org/uniprot/Q9DAA4 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although related to peptidase S1 family, lacks the conserved active Ser residue in position 192 which is replaced by an Ala, suggesting that it has no protease activity. Lacks also metal binding sites Glu in position 67 which is replaced by Asn and Asn in position 69 which is replaced by Lys.|||Belongs to the peptidase S1 family.|||Expressed exclusively in the spermatids at steps 9-14 of spermiogenesis (PubMed:23553430).|||Mice exhibit male infertility, but their mating behavior, spermatogenesis, sperm morphology and motility remain unaffected (PubMed:23553430). Male sperm migration from uterus into oviduct and zona-intact oocyte binding are impaired; however, sperm is still able to fertilize cumulus-intact oocytes (PubMed:23553430). Male show an absence of mature ADAM3 in sperm (PubMed:23553430).|||Plays a role in male fertility (PubMed:23553430). May have a role in sperm migration or binding to zona-intact eggs (PubMed:23553430). Involved in the activation of the proacrosin/acrosin system (By similarity).|||Secreted|||Testis-specific (PubMed:23553430). Expressed in spermatids (PubMed:23553430). Weakly expressed in mature sperm (at protein level) (PubMed:23553430).|||acrosome http://togogenome.org/gene/10090:Dcun1d2 ^@ http://purl.uniprot.org/uniprot/Q8BZJ7 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes and plays an essential role in the regulation of SCF (SKP1-CUL1-F-box protein)-type complexes activity.|||Cytoplasm|||Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. May also interact with regulators or subunits of cullin-RING ligases such as RBX1, RNF7, ELOB and DDB1; these interactions are bridged by cullins. Interacts with CAND1; this interaction is bridged by cullins such as CUL3 and strongly inhibits the neddylation of CUL3. These CAND-cullin-DCNL complexes can only be neddylated in the presence of a substrate adapter. Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F.|||Nucleus|||Splicing donor and acceptor site not canonical.|||The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities. http://togogenome.org/gene/10090:Cenpc1 ^@ http://purl.uniprot.org/uniprot/P49452|||http://purl.uniprot.org/uniprot/Q3UPF6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-C/MIF2 family.|||Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions.|||Nucleus|||Oligomer. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. Binds to DAXX. Interacts with DNMT3B. Interacts directly with CENPA. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1 (By similarity). Interacts with MEIKIN (PubMed:25533956).|||The MIF2 homology domain II targets centromeres and binds the alpha satellite DNA in vivo. The MIF2 homology domain III can induce CENPC dimerization/oligomerization.|||centromere|||kinetochore http://togogenome.org/gene/10090:Or4a68 ^@ http://purl.uniprot.org/uniprot/Q8VG73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pomp ^@ http://purl.uniprot.org/uniprot/Q9CQT5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POMP/UMP1 family.|||By interferon gamma.|||Constituent of preproteasomes, but not of mature 20S proteasomes. Within the preproteasome, may directly interact with PSMB1/beta6, PSMB4/beta7, PSMB5/beta5, PSMB6/beta1 and PSMB9/beta1i. Interaction with PSMB8/beta5i is controversial. Forms tetramers (By similarity).|||Microsome membrane|||Molecular chaperone essential for the assembly of standard proteasomes and immunoproteasomes. Degraded after completion of proteasome maturation (By similarity). Mediates the association of 20S preproteasome with the endoplasmic reticulum (By similarity).|||Nucleus|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Wdr74 ^@ http://purl.uniprot.org/uniprot/Q8VCG3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Expressed at low levels in MII oocytes and 1-cell embryos and increases through subsequent cleavage stage divisions. The peak of mRNA expression occurs at the morula stage, with a slight decrease in blastocyst embryos.|||Isoform 1 interacts (through WDR repeats) with NVL; the interaction is independent of RNA or pre-60S ribosome particles. Isoform 2 does not interact with NVL. Interacts with MTREX; the interaction dissociation in a late stage of rRNA synthesis is required for appropriate maturation of pre-60S particles and depends on the ATPase activity of NVL.|||Nucleus|||Regulatory protein of the MTREX-exosome complex involved in the synthesis of the 60S ribosomal subunit. Participates in an early cleavage of the pre-rRNA processing pathway in cooperation with NVL (By similarity). Required for blastocyst formation, is necessary for RNA transcription, processing and/or stability during preimplantation development (PubMed:21799883).|||nucleolus http://togogenome.org/gene/10090:Tardbp ^@ http://purl.uniprot.org/uniprot/Q544R5|||http://purl.uniprot.org/uniprot/Q6VYI4|||http://purl.uniprot.org/uniprot/Q6VYI5|||http://purl.uniprot.org/uniprot/Q8BLD4|||http://purl.uniprot.org/uniprot/Q8BUM1|||http://purl.uniprot.org/uniprot/Q8R0B4|||http://purl.uniprot.org/uniprot/Q921F2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Homooligomer (via its N-terminal domain) (By similarity). Interacts with BRDT (PubMed:22570411). Binds specifically to pyrimidine-rich motifs of TAR DNA and to single stranded TG repeated sequences. Binds to RNA, specifically to UG repeated sequences with a minimum of six contiguous repeats. Interacts with ATXN2; the interaction is RNA-dependent. Interacts with MATR3. Interacts with UBQLN2. Interacts with HNRNPA2B1 (By similarity). Interacts with ZNF106 (PubMed:28072389). Interacts with CNOT7/CAF1 (By similarity). Interacts with CRY2 (PubMed:27123980). Interacts with PPIA/CYPA; the interaction is dependent on RNA-binding activity of TARDBP and PPIase activity of PPIA/CYPA (PubMed:25678563). Acetylation of PPIA/CYPA at 'Lys-125' favors the interaction of TARDBP with PPIA/CYPA (By similarity).|||Hyperphosphorylated.|||Mitochondrion|||Nucleus|||RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs. In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases. Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts. Regulates also mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening. In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (By similarity). Participates also in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (By similarity). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563).|||Stress granule|||TARDBP depletion leads to atrophy of spinal motor neurons. Affects motor axon, neuromuscular junction and skeletal muscle.|||The RRM domains can bind to both DNA and RNA.|||Ubiquitinated. http://togogenome.org/gene/10090:Or5m13b ^@ http://purl.uniprot.org/uniprot/Q7TR90 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp2c69 ^@ http://purl.uniprot.org/uniprot/E9PXC3 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Slc49a3 ^@ http://purl.uniprot.org/uniprot/Q8CE47 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Membrane http://togogenome.org/gene/10090:Marco ^@ http://purl.uniprot.org/uniprot/A2RT24|||http://purl.uniprot.org/uniprot/Q60754 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in subpopulations of macrophages in the spleen and the medullary cord of lymph nodes (at protein level).|||Homotrimer; disulfide-linked (PubMed:7867067). Trimers may assemble in larger oligomers thus resulting in the creation of a large surface capable of interacting with very large ligands (PubMed:17405873).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||N-glycosylated.|||Pattern recognition receptor (PRR) which binds Gram-positive and Gram-negative bacteria (PubMed:7867067). Also plays a role in binding of unopsonized particles by alveolar macrophages (By similarity). Binds to the secretoglobin SCGB3A2 (By similarity). http://togogenome.org/gene/10090:Vmn1r205 ^@ http://purl.uniprot.org/uniprot/Q8R276 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hs6st1 ^@ http://purl.uniprot.org/uniprot/Q9QYK5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate. Critical for normal neuronal development where it may play a role in neuron branching. May also play a role in limb development. May prefer iduronic acid.|||According to PubMed:17405882 most mice die between embryonic day 15.5 and the perinatal stage. Those that survive are considerably smaller than their wild-type littermates and exhibit development abnormalities including a reduction in the number of fetal microvessels in the labyrinthine zone of the placenta. However, according to PubMed:18196599, pups are viable and grossly normal at birth. During early adulthood, however, mice fail to thrive and exhibit growth retardation, bodyweight loss, enlargement of airspaces in the lung and, in some cases, lethality.|||Belongs to the sulfotransferase 6 family.|||Expressed in fetal brain and liver.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Klk8 ^@ http://purl.uniprot.org/uniprot/Q61955 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||By chemical/incision-induced brain injury which leads to increased expression in axon fiber bundles of the peri-lesioned region, by electrically-induced seizure (kindling) in brain, by UV irradiation in skin and by incisional and chemically-induced skin wounding which causes epidermal proliferation and hyperkeratosis. Induced by chemically-induced oxidative stress which leads to increased expression in the hippocampal pyramidal neurons 2 hours after treatment. Levels then decrease, drop to 60% of pretreated control levels at day 7 when avoidance learning is impaired and return to control levels at day 30. Also induced by spinal crush injury which leads to increased expression in spinal cord white matter adjacent to the lesion. Expression increases between days 1-14 post-injury with a peak at day 4.|||Cytoplasm|||Expressed in the limbic system of mouse brain and is localized at highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields. Also detected in spinal cord gray matter and in keratinized stratified epithelia of epidermis, hair, tongue, palate, nasal cavity, pharynges, esophagus and forestomach. In skin and mucus membranes, expressed in stratum spinosum and stratum granulosum. Expressed during estrus in vaginal epithelial cells but not stromal cells. Within the vaginal epithelium, expressed in prickle cells, granular cells and parakeratotic cells but not in basal cells. Not expressed in uterus. Expressed in the keratinocytes.|||Expression is detected in the brain from embryonic day 12 and continues into adulthood.|||Interacts with SPINK9.|||Mice display marked abnormalities of synapses and neurons in the CA1 subfield of the hippocampus with enlarged and elongated pyramidal cell soma and reduced asymmetrical synapse numbers. Mutants also display impaired spatial memory acquisition, increased hippocampal susceptibility to hyperexcitability in response to repetitive afferent stimulation and prolonged recovery of UV-irradiated skin. Following spinal cord injury, mutants display reduced demyelination, oligodendrocyte death and axonal degeneration, and inproved hind limb recovery, suggesting that attenuation of neuropsin activity may be beneficial in the treatment of spinal cord injury. Blocking of Klk8 activity by intraventricular injection with monoclonal antibodies reduces or eliminates epileptic seizures in kindled mice.|||Secreted|||Serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. Also cleaves L1CAM in response to increased neural activity. Induces neurite outgrowth and fasciculation of cultured hippocampal neurons. Plays a role in the formation and maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway, regulates Schaffer-collateral long-term potentiation in the hippocampus and is required for memory acquisition and synaptic plasticity. Involved in skin desquamation and keratinocyte proliferation. Plays a role in the secondary phase of pathogenesis following spinal cord injury.|||Strongly inhibited by diisopropyl fluorophosphate, leupeptin and (4-amidinophenyl)methanesulfonyl 1-fluoride. http://togogenome.org/gene/10090:Cenpx ^@ http://purl.uniprot.org/uniprot/A2AC07|||http://purl.uniprot.org/uniprot/Q8C4X1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-X/MHF2 family.|||By retinoic acid.|||DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage. In complex with CENPS (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM. In complex with CENPS and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks. In complex with CENPS, CENPT and CENPW (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression. As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure. DNA-binding function is fulfilled in the presence of CENPS, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own.|||Heterodimer with CENPX, sometimes called MHF; this interaction stabilizes both partners. MHF heterodimers can assemble to form tetrameric structures. MHF also coassemble with CENPT-CENPW heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex. Forms a discrete complex with FANCM and CENPX, called FANCM-MHF; this interaction, probably mediated by direct binding between CENPS and FANCM, leads to synergistic activation of double-stranded DNA binding and strongly stimulates FANCM-mediated DNA remodeling. Recruited by FANCM to the Fanconi anemia (FA) core complex, which consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FAAP24 and FAAP100. The FA core complex associates with Bloom syndrome (BLM) complex, which consists of at least BLM, DNA topoisomerase 3-alpha (TOP3A), RMI1/BLAP75, RPA1/RPA70 and RPA2/RPA32. The super complex between FA and BLM is called BRAFT.|||Nucleus|||centromere|||kinetochore http://togogenome.org/gene/10090:Dcun1d4 ^@ http://purl.uniprot.org/uniprot/Q8CCA0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which are necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).|||Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Interacts with RBX1 and RNF7. Interacts with CAND1; this interaction is bridged by cullins such as CUL3 and strongly inhibits the neddylation of CUL3. These CAND-cullin-DCNL complexes can only be neddylated in the presence of a substrate adapter. Interacts (via DCUN1 domain) with UBE2M (N-terminally acetylated form) and probably with UBE2F (N-terminally acetylated form).|||Nucleus|||The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities. http://togogenome.org/gene/10090:Syk ^@ http://purl.uniprot.org/uniprot/P48025|||http://purl.uniprot.org/uniprot/Q3UPF7|||http://purl.uniprot.org/uniprot/Q6P1E0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation (By similarity). Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity).|||Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-317 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-342 creates a binding site for VAV1 (By similarity). Phosphorylation on Tyr-342 and Tyr-346 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway (By similarity). Phosphorylated on tyrosine residues in response to IL15 (By similarity). Phosphorylation on Ser-291 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG (By similarity). Phosphorylation at Tyr-624 creates a binding site for BLNK (By similarity). Dephosphorylated by PTPN6 (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.|||Cell membrane|||Embryos display severe systemic hemorrhage and mice are not viable dying perinatally. While T-cells development is not affected, the development of B-cells is impaired most probably at the pro-B to pre-B transition and mice lack mature B-cells.|||Interacts with LYN; phosphorylates SYK. Interacts with RHOH (phosphorylated); regulates mast cells activation. Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling. Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation (By similarity). Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling. Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation. Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation. Interaction with FCER1G in basophils triggers IL3-induced IL4 production (PubMed:19098920). Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling. Interacts with ITGB3; upon activation by ITGB3 promotes platelet adhesion (By similarity). Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in neutrophils and macrophages integrin-mediated activation. Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG (By similarity). Interacts with BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels (By similarity). Interacts (via SH2 domains) with CLEC1B (dimer) (By similarity). Interacts with CLEC7A; participates in leukocyte activation in presence of fungal pathogens. Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment (By similarity). Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK (By similarity). Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity (By similarity). Interacts with TNS2; leading to the phosphorylation of SYK (By similarity). Interacts with FLNA (via filamin repeat 5); docks SYK to the plasma membrane (By similarity). Interacts with CEACAM1; lipopolysaccharide activated neutrophils induce phosphorylation of SYK resulting in the formation of a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity (PubMed:22496641). Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); the interaction further enhances CEACAM20 phosphorylation (PubMed:26195794). Interacts with IL15RA (By similarity).|||Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Required for the stimulation of neutrophil phagocytosis by IL15 (By similarity). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (PubMed:19098920). Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (PubMed:26195794).|||The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization (By similarity).|||Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.|||cytosol|||phagosome http://togogenome.org/gene/10090:Slc15a3 ^@ http://purl.uniprot.org/uniprot/Q8BPX9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.|||Endosome membrane|||Expressed highly in bone marrow derived macrophages, and weakly in spleen and lung (PubMed:11004510). Expressed in plasmacytoid dendritic cells (pDCs) in response to toll-like receptors (TLR) stimulation (PubMed:24695226).|||Lysosome membrane|||Proton-coupled amino-acid transporter that transports free histidine and certain di- and tripeptides, and is involved in innate immune response (PubMed:24695226). Also able to transport carnosine (By similarity). Involved in the detection of microbial pathogens by toll-like receptors (TLRs) and NOD-like receptors (NLRs), probably by mediating transport of bacterial peptidoglycans across the endolysosomal membrane: catalyzes the transport of certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand (PubMed:24695226). http://togogenome.org/gene/10090:Dnajc19 ^@ http://purl.uniprot.org/uniprot/Q9CQV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TIM14 family.|||Interacts with PHB2; the interaction associates DNAJC19 with the prohibitin complex (PubMed:24856930). Interacts with TIMM16/PAM16 (PubMed:24856930). May be a component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19 (By similarity).|||Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling (PubMed:24856930). May be a component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Zfp697 ^@ http://purl.uniprot.org/uniprot/Q569E7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Hapln2 ^@ http://purl.uniprot.org/uniprot/B2RRU7|||http://purl.uniprot.org/uniprot/Q9ESM3 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HAPLN family.|||Brain. Predominantly expressed by neurons. Colocalizes with versican V2 in developing and adult cerebellar white matter and at the nodes of Ranvier.|||Expression starts at postnatal day 20 and increases thereafter.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates a firm binding of versican V2 to hyaluronic acid. May play a pivotal role in the formation of the hyaluronan-associated matrix in the central nervous system (CNS) which facilitates neuronal conduction and general structural stabilization. Binds to hyaluronic acid.|||extracellular matrix http://togogenome.org/gene/10090:Ltb4r1 ^@ http://purl.uniprot.org/uniprot/A7VJD3|||http://purl.uniprot.org/uniprot/O88855 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the chemokine-like receptor (CMKLR) family.|||Cell membrane|||Highly expressed on activated leukocytes, including eosinophils.|||Membrane|||Phosphorylated by GRK6 upon leukotriene B4 binding; which promotes desensitization.|||Receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response. http://togogenome.org/gene/10090:Kitl ^@ http://purl.uniprot.org/uniprot/P20826 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble form is produced by proteolytic processing of isoform 1 in the extracellular domain.|||Acts in the early stages of hematopoiesis.|||Belongs to the SCF family.|||Cell membrane|||Cytoplasm|||Expressed in the cochlea.|||Homodimer, non-covalently linked (Probable). Heterotetramer with KIT, binding two KIT molecules; thereby mediates KIT dimerization and subsequent activation by autophosphorylation.|||Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.|||Secreted|||cytoskeleton|||filopodium|||lamellipodium http://togogenome.org/gene/10090:Rpl28 ^@ http://purl.uniprot.org/uniprot/P41105|||http://purl.uniprot.org/uniprot/Q5M9J8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL28 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Pik3c2g ^@ http://purl.uniprot.org/uniprot/O70167 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PI3/PI4-kinase family.|||Expressed predominantly in liver. Also found in kidney, lung and lymphoid tissue. Down-regulated in BeF3 cells expressing the BCR-ABL oncogene p185.|||Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers (PubMed:9514948). May play a role in SDF1A-stimulated chemotaxis.|||Membrane http://togogenome.org/gene/10090:Pitrm1 ^@ http://purl.uniprot.org/uniprot/Q8K411 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A disulfide bond locks the enzyme in the closed conformation preventing substrate entry into the catalytic chamber.|||Belongs to the peptidase M16 family. PreP subfamily.|||Binds 1 zinc ion per subunit.|||Mainly exists in a closed and catalytically competent conformation but a closed-to-open switch allows substrate entry into the catalytic chamber. Substrate binding induces closure and dimerization. A disulfide bond may lock the enzyme in a closed conformation preventing substrate entry into the catalytic chamber, participating in redox regulation of the enzyme. Inhibited by metal-chelating agents. Inhibited by nickel and zinc excess, and slightly activated by manganese.|||Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing. Has an ATP-independent activity. Specifically cleaves peptides in the range of 5 to 65 residues. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference. Degrades the transit peptides of mitochondrial proteins after their cleavage. Also degrades other unstructured peptides. It is also able to degrade amyloid-beta protein 40, one of the peptides produced by APP processing, when it accumulates in mitochondrion. It is a highly efficient protease, at least toward amyloid-beta protein 40. Cleaves that peptide at a specific position and is probably not processive, releasing digested peptides intermediates that can be further cleaved subsequently. It is also able to degrade amyloid-beta protein 42.|||Mitochondrion matrix|||Monomer and homodimer; homodimerization is induced by binding of the substrate.|||Up-regulated transplantes nuclei derived from embryonic stem (ES) cells. http://togogenome.org/gene/10090:Htr4 ^@ http://purl.uniprot.org/uniprot/A0A494BA82|||http://purl.uniprot.org/uniprot/P97288 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Endosome|||Isoform 5-HT4(A) interacts with MAGI2, MPP3, NHERF1 and SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with PATJ, NOS1 and SEC23A. Isoform 5-HT4(A) forms a complex including NHERF1 and EZR. Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin) (By similarity).|||Membrane|||This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase (By similarity).|||This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. http://togogenome.org/gene/10090:Cst8 ^@ http://purl.uniprot.org/uniprot/P32766 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Performs a specialized role during sperm development and maturation.|||Proximal caput region of the epididymis. Lower expression in the testis. Within the testis it is localized to the elongating spermatids, whereas within the epididymis it is exclusively synthesized by the proximal caput epithelium.|||Secreted|||Testicular factors or hormones other than androgens present in the testicular fluid may be involved in the regulation of CRES gene expression. http://togogenome.org/gene/10090:Krt88 ^@ http://purl.uniprot.org/uniprot/Q9CPR6 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:H2-Eb1 ^@ http://purl.uniprot.org/uniprot/O78196 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Ranbp3l ^@ http://purl.uniprot.org/uniprot/Q6PDH4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with SMAD1, SMAD5 and SMAD8.|||Nuclear export factor for BMP-specific SMAD1/5/8 that plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation by blocking osteoblast differentiation to promote myogenic differention. Directly recognizes dephosphorylated SMAD1/5/8 and mediates their nuclear export in a Ran-dependent manner.|||Nucleus http://togogenome.org/gene/10090:Tfpt ^@ http://purl.uniprot.org/uniprot/Q3U1J1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Appears to promote apoptosis in a p53/TP53-independent manner.|||Interacts with NOL3; translocates NOL3 into the nucleus and negatively regulated TFPT-induced cell death. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80 (By similarity).|||Nucleus|||Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. http://togogenome.org/gene/10090:Ing5 ^@ http://purl.uniprot.org/uniprot/Q9D8Y8 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ING family.|||Chromosome|||Component of the HBO1 complex composed of KAT7/HBO1, MEAF6, ING5, and one scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE scaffold (JADE1, JADE2 and JADE3) mediate acetylation of histone H4. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with H3K4me3 and to a lesser extent with H3K4me2. Interacts with EP300 and p53/TP53. Interacts with INCA1.|||Component of the HBO1 complex, which specifically mediates acetylation of histone H3 at 'Lys-14' (H3K14ac) and, to a lower extent, acetylation of histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. Through chromatin acetylation it may regulate DNA replication and may function as a transcriptional coactivator. Inhibits cell growth, induces a delay in S-phase progression and enhances Fas-induced apoptosis in an INCA1-dependent manner.|||May be due to a competing acceptor splice site.|||Nucleus|||The PHD-type zinc finger mediates the binding to H3K4me3. http://togogenome.org/gene/10090:Wfikkn2 ^@ http://purl.uniprot.org/uniprot/Q7TQN3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WFIKKN family.|||Interacts with both mature and propeptide myostatin/MSTN.|||Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease- and metalloprotease-inhibitor activity (By similarity). Inhibits the biological activity of mature myostatin, but not activin.|||Secreted|||Widely expressed, with high expression in skeletal muscle and heart. Also expressed in brain, lung and testis. Weakly expressed in liver and kidney. http://togogenome.org/gene/10090:Krtap19-1 ^@ http://purl.uniprot.org/uniprot/G3XA43 ^@ Function|||Subunit ^@ In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Hoxa10 ^@ http://purl.uniprot.org/uniprot/P31310 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Abd-B homeobox family.|||Embryonic expression increases from day 9 to day 12 and then declines to day 15.|||Expressed in the developing limb bud where it is restricted to the mesenchyme along the proximal-distal axis. Also found in developing gut and urogenital tract. In adult tissue, both forms found in kidney but only isoform 1 is expressed in skeletal muscle.|||Interacts with SIRT2; the interaction is direct.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to the DNA sequence 5'-AA[AT]TTTTATTAC-3'. http://togogenome.org/gene/10090:Ephb1 ^@ http://purl.uniprot.org/uniprot/Q8CBF3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Early endosome membrane|||Expressed in growth cones of ventrotemporal (uncrossed) retinal ganglion cells that give rise to ipsilateral projections (at protein level) (PubMed:12971893, PubMed:18524895). In myogenic progenitor cells, initially expressed early during myogenic development (11.5 dpc), down-regulated during the fetal stage (lower levels at 17.5 dpc) to be re-expressed in postnatal satellite cells (PubMed:27446912).|||Expressed in neural stem and progenitor cells in the dentate gyrus (PubMed:18057206). Expressed in myogenic progenitor cells (PubMed:27446912).|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts with EPHB6; transphosphorylates EPHB6 to form an active signaling complex (By similarity). Interacts with PICK1. Interacts (through Tyr-594) with NCK1 (via SH2 domain); activates the JUN cascade to regulate cell adhesion. The ligand-activated form interacts (through Tyr-928) with GRB7 and GRB10 (via SH2 domains). The ligand-activated form interacts (residues within the catalytic domain) with GRB2 (via SH2 domain). Interacts with GRB2, SHC1 and SRC; activates the MAPK/ERK cascade to regulate cell migration. Interacts with CBL; regulates receptor degradation through ubiquitination. Interacts with ACP1.|||Mice development is apparently normal. However, they display a dramatic reduction of ipsilateral retinal projection. Mice do not develop neuropathic algesia and physical dependence to morphine.|||Phosphorylated. Autophosphorylation is stimulated by the ligand EFNB1. Required for interaction with SH2 domain-containing interactors, for activation of the MAPK/ERK and JUN signaling cascades and for ubiquitination by CBL (By similarity).|||Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (PubMed:27446912).|||Ubiquitinated; (EFNB1)ligand-induced poly- and/or multi-ubiquitination by CBL is regulated by SRC and leads to lysosomal degradation.|||dendrite http://togogenome.org/gene/10090:Stfa1 ^@ http://purl.uniprot.org/uniprot/P35175 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cystatin family.|||Cytoplasm|||This is an intracellular thiol proteinase inhibitor. http://togogenome.org/gene/10090:Tuba3a ^@ http://purl.uniprot.org/uniprot/P05214|||http://purl.uniprot.org/uniprot/Q5FW91 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.|||Alpha-3 and alpha-7 are identical but coded by two different genes, they are testis-specific.|||Belongs to the tubulin family.|||Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488).|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.|||Nitration of Tyr-450 is irreversible and interferes with normal dynein intracellular distribution.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREC motif may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).|||Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.|||cytoskeleton http://togogenome.org/gene/10090:Igfn1 ^@ http://purl.uniprot.org/uniprot/Q3KNY0 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with FLNC. Interacts with KY.|||Isoform 1, isoform 3 and isoform 4 are expressed in skeletal muscle while isoform 2 is detected in both skeletal muscle and heart (at protein level).|||Nucleus|||Z line http://togogenome.org/gene/10090:Cstdc1 ^@ http://purl.uniprot.org/uniprot/Q8VII3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Located only in seminiferous tubules (at protein level). Expressed in testis and Sertoli cells.|||May play a specialized role in spermatogenesis.|||Secreted http://togogenome.org/gene/10090:Gm5934 ^@ http://purl.uniprot.org/uniprot/D3Z4U6 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Slc25a5 ^@ http://purl.uniprot.org/uniprot/P51881|||http://purl.uniprot.org/uniprot/Q545A2 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:31341297). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31489369, PubMed:31341297). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (PubMed:31341297). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A5/ANT2 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (PubMed:31341297). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (PubMed:31341297). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (PubMed:31341297). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31489369). It is however unclear if SLC25A5/ANT2 constitutes a pore-forming component of mPTP or regulates it (PubMed:31489369). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756). As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (By similarity).|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Catalyzes the exchange of ADP and ATP across the membrane.|||It is unclear if SLC25A4/ANT1 constitutes a pore-forming component of mitochondrial permeability transition pore (mPTP) (PubMed:14749836, PubMed:31489369). Initial reports, based on deletion of Slc25a4/Ant1 and Slc25a5/Ant2, suggested that ADP/ATP translocase rather acts as a regulator of mPTP (PubMed:14749836). However, deletion of all ADP/ATP translocase components (Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4) completely inhibits mPTP, suggesting that ADP/ATP translocase constitutes a pore-forming component of mPTP (PubMed:31489369). Discrepancy between reports may be caused by overexpression of Slc25a31/Ant4 in mice lacking Slc25a4/Ant1 and Slc25a5/Ant2, which compensates for the loss of Slc25a4/Ant1 and Slc25a5/Ant2 (PubMed:31489369).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mice show an apparently normal embryonic development except pale phenotype, but show a reduced birth rate (PubMed:25613378). Postnatal growth is severely retarded with macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, causing lethality within 4 weeks (PubMed:25613378). Mice develop anemia in a cell-autonomous manner by maturation arrest of erythroid precursors with increased reactive oxygen species and premature deaths (PubMed:25613378). B-lymphocyte development is also affected: splenocytes show a reduction in maximal respiration capacity and cellular ATP levels as well as an increase in cell death accompanying mitochondrial permeability transition pore opening (PubMed:25613378). Cells display impaired mitochondrial uncoupling (PubMed:31341297). Cells show impaired autophagy, leading to accumulation of aberrant mitochondria (PubMed:31618756). Mice lacking Slc25a4/Ant1 and Slc25a5/Ant2 in liver still have mitochondrial permeability transition pore (mPTP) activity, although more Ca(2+) is required to activate the mPTP (PubMed:14749836). Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mPTP (PubMed:31489369). Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca(2+)-induced mPTP formation (PubMed:31489369).|||Mitochondrion inner membrane|||Monomer (By similarity). Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5/ANT2. Interacts with AK4 (By similarity). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756).|||Monomer.|||The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297).|||The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.|||Trimethylated by ANTKMT at Lys-52.|||Widely expressed. http://togogenome.org/gene/10090:Lin7c ^@ http://purl.uniprot.org/uniprot/O88952 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the lin-7 family.|||Cell junction|||Cell membrane|||Expressed in the kidney; particularly in the outer medullary collecting duct.|||Forms a complex with CASK and CASKIN1 (By similarity). Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (PubMed:10846156). Can also interact with other modular proteins containing protein-protein interaction domains like PALS1, PALS2, MPP7, DLG1, DLG2 and DLG3 through its L27 domain. Interacts with DLG4 and GRIN2B as well as CDH1 and CTNNB1, the channels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably KCNJ2/Kir2.1 and SLC6A12/BGT-1 via its PDZ domain. The association of LIN7A with cadherin and beta-catenin is calcium-dependent, occurs at synaptic junctions and requires the actin cytoskeleton. Interacts with EGFR, ERBB2, ERBB3 and ERBB4 with both PDZ and KID domains. Associates with KIF17 via APBA1. Interacts with HTR4. Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C) (By similarity). Interacts with MAPK12.|||Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (PubMed:10846156). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells.|||Postsynaptic density membrane|||The L27 domain mediates interaction with CASK and is involved in the formation of multimeric complexes and the association of LIN7 to membranes.|||The PDZ domain regulates endocytosis and recycling of the receptor at the membrane.|||The kinase interacting site is required for proper delivery of ERBB2 to the basolateral membrane.|||tight junction http://togogenome.org/gene/10090:Atp1a2 ^@ http://purl.uniprot.org/uniprot/Q3UHK5|||http://purl.uniprot.org/uniprot/Q6PIE5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with regulatory subunit FXYD1.|||This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (By similarity). http://togogenome.org/gene/10090:ATP8 ^@ http://purl.uniprot.org/uniprot/P03930|||http://purl.uniprot.org/uniprot/Q7JCZ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase protein 8 family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). Interacts with PRICKLE3 (By similarity).|||Membrane|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.|||Mitochondrion membrane http://togogenome.org/gene/10090:Cryba4 ^@ http://purl.uniprot.org/uniprot/E9QAS6|||http://purl.uniprot.org/uniprot/Q3V1A0|||http://purl.uniprot.org/uniprot/Q9JJV0 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms (By similarity). http://togogenome.org/gene/10090:Dpysl5 ^@ http://purl.uniprot.org/uniprot/Q9EQF6 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.|||Cytoplasm|||Detected in brain.|||Detected in whole embryos after 11 days of development. Detected in embryonic head. Highly expressed in newborns and up to 7 days after birth. Expression is decreased after 14 days.|||Homotetramer, and heterotetramer with other DPYS-like proteins. Interacts with DPYSL2, DPYSL3 and DPYSL4. Interacts with SEPTIN4 isoform 4. Interacts with MAP2 and TUBB3 (By similarity).|||Involved in the negative regulation of dendrite outgrowth.|||Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure. http://togogenome.org/gene/10090:Cmc1 ^@ http://purl.uniprot.org/uniprot/Q9CPZ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CMC family.|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14.|||Mitochondrion http://togogenome.org/gene/10090:Esyt3 ^@ http://purl.uniprot.org/uniprot/Q5DTI8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the extended synaptotagmin family.|||Cell membrane|||Endoplasmic reticulum membrane|||Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity).|||The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior (By similarity). http://togogenome.org/gene/10090:Cad ^@ http://purl.uniprot.org/uniprot/B2RQC6 ^@ Activity Regulation|||Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by MAP kinase (Erk1/2) phosphorylation just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. Phosphorylation at Ser-1859 by RPS6KB1 downstream of MTOR promotes oligomerization and stimulates dihydroorotase activity. Phosphorylation at Ser-1406 reduces sensitivity to feedback inhibition by UTP (By similarity).|||Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction (By similarity).|||Binds 3 Zn(2+) ions per subunit (for dihydroorotase activity).|||Binds 4 magnesium or manganese ions per subunit.|||Cytoplasm|||GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC 6.3.5.5).|||Homohexamer. Interacts with CIPC.|||In the central section; belongs to the metallo-dependent hydrolases superfamily. DHOase family. CAD subfamily.|||Nucleus|||This protein is a 'fusion' protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). http://togogenome.org/gene/10090:Rps7 ^@ http://purl.uniprot.org/uniprot/P62082|||http://purl.uniprot.org/uniprot/Q4FZE6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS7 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity). Binds IPO9 with high affinity (By similarity). Interacts with NEK6 (By similarity). Interacts with DESI2 (By similarity). Interacts with IPO5, IPO7 and KPNB1; these interactions may be involved in RPS7 nuclear import for the assembly of ribosomal subunits (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Required for rRNA maturation (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Phosphorylated by NEK6.|||Ubiquitinated. Deubiquitinated by DESI2, leading to its stabilization.|||centrosome|||nucleolus http://togogenome.org/gene/10090:Nsfl1c ^@ http://purl.uniprot.org/uniprot/Q3UVN5|||http://purl.uniprot.org/uniprot/Q9CZ44 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NSFL1C family.|||Chromosome|||Golgi stack|||Nucleus|||Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Binds ubiquitin and mono-ubiquitinated proteins via its N-terminal UBA-like domain when bound to VCP (By similarity).|||Part of a ternary complex containing STX5A, NSFL1C and VCP. NSFL1C forms a homotrimer that binds to one end of a VCP homohexamer. The complex binds to membranes enriched in phosphatidylethanolamine-containing lipids and promotes Golgi membrane fusion. Interaction with VCIP135 leads to dissociation of the complex via ATP hydrolysis by VCP. Binds ubiquitin and mono-ubiquitinated proteins via its N-terminal UBA-like domain when bound to VCP.|||Phosphorylated during mitosis. Phosphorylation inhibits interaction with Golgi membranes and is required for the fragmentation of the Golgi stacks during mitosis (By similarity).|||Reduces the ATPase activity of VCP. Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis. May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER). Inhibits the activity of CTSL (in vitro). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase. Also, regulates spindle orientation during mitosis.|||centrosome http://togogenome.org/gene/10090:Vmn1r18 ^@ http://purl.uniprot.org/uniprot/Q8R2C8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aco2 ^@ http://purl.uniprot.org/uniprot/Q99KI0 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aconitase/IPM isomerase family.|||Binds 1 [4Fe-4S] cluster per subunit. Binding of a [3Fe-4S] cluster leads to an inactive enzyme.|||Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.|||Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers.|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Spocd1 ^@ http://purl.uniprot.org/uniprot/B1ASB6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Detected in embryonic testis at 14.5 dpc and decreases by postnatal day 5.|||Essential excecutor of PIWIL4-piRNA pathway directed transposon DNA methylation and silencing in the male embryonic germ cells (PubMed:32674113). Associates with the de novo DNA methylation machinery and repressive chromatin remodeling complexes (PubMed:32674113). Tethering of PIWIL4 to a nascent transposable element transcript recruits repressive chromatin remodeling activities and the de novo methylation apparatus through SPOCD1 (PubMed:32674113). Not required for piRNA biosynthesis (PubMed:32674113).|||Interacts with DNMT3A, DNMT3C and DNMT3L.|||Male mice are infertile with spermatozoa completely absent in the epididymis (PubMed:32674113). Male germ cells show derepression of transposable elements (TEs) and DNA hypomethylation of TEs (PubMed:32674113).|||Nucleus http://togogenome.org/gene/10090:Plekhm3 ^@ http://purl.uniprot.org/uniprot/Q8BM47 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Golgi apparatus|||Interacts with AKT1.|||Involved in skeletal muscle differentiation (PubMed:19028694). May act as a scaffold protein for AKT1 during muscle differentiation (PubMed:19028694).|||Widely expressed (PubMed:19028694). Expressed in C2C12 cells (at protein level) (PubMed:19028694). http://togogenome.org/gene/10090:Elk1 ^@ http://purl.uniprot.org/uniprot/P41969 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Interacts in its sumoylated form with PIAS2/PIASX which enhances its transcriptional activator activity. Interacts with MAD2L2; the interaction is direct and promotes phosphorylation by the kinases MAPK8 and/or MAPK9. Interacts with POU1F1.|||Nucleus|||On mitogenic stimulation, phosphorylated on C-terminal serine and threonine residues by MAPK1 but also MAPK8 and/or MAPK9. Phosphorylation leads to loss of sumoylation and restores transcriptional activator activity. Phosphorylated and activated by CaMK4, MAPK11, MAPK12 and MAPK14 (By similarity). Upon bFGF stimulus, phosphorylated by PAK1 (By similarity).|||Predominantly expressed in the brain, and to a lesser extent in the heart, liver and muscle.|||Sumoylation represses transcriptional activator activity as it results in recruitment of HDAC2 to target gene promoters which leads to decreased histone acetylation and reduced transactivator activity. It also regulates nuclear retention (By similarity).|||Transcription factor that binds to purine-rich DNA sequences. Forms a ternary complex with SRF and the ETS and SRF motifs of the serum response element (SRE) on the promoter region of immediate early genes such as FOS and IER2 (By similarity). Induces target gene transcription upon JNK-signaling pathway stimulation (By similarity). http://togogenome.org/gene/10090:Pou5f2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J273|||http://purl.uniprot.org/uniprot/Q9DAC9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the POU transcription factor family.|||Belongs to the POU transcription factor family. Class-5 subfamily.|||In adult brain, expressed in the olfactory bulb, becoming specifically concentrated in the mitral cell layer. Also found in the pyramidal cell layer of the hippocampus, in the granule cell layer of the cerebellum and in the cortex.|||Low expression levels observed at 12 dpc in neural tube and brain. On days 15.5 and 16.5, expression levels increased and became localized specifically to the forebrain, with highest levels found in the laminar region of the forebrain cortex. Also expressed in the mitral region of the olfactory bulb.|||Nucleus|||Transcription factor that binds preferentially to the octamer motif (5'-ATGTTAAT-3'). May exert a regulatory function in meiotic events that are required for terminal differentiation of male germ cell (By similarity). http://togogenome.org/gene/10090:Rbm3 ^@ http://purl.uniprot.org/uniprot/O89086|||http://purl.uniprot.org/uniprot/Q545K5|||http://purl.uniprot.org/uniprot/Q5RJV3|||http://purl.uniprot.org/uniprot/Q8BG13 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Arg-103 is dimethylated, probably to asymmetric dimethylarginine.|||Cold-inducible mRNA binding protein that enhances global protein synthesis at both physiological and mild hypothermic temperatures. Reduces the relative abundance of microRNAs, when overexpressed. Enhances phosphorylation of translation initiation factors and active polysome formation.|||Cytoplasm|||Interacts with RPL4. Associates with the 60S ribosomal subunits in an RNA-independent manner.|||Nucleus|||Phosphorylated.|||dendrite http://togogenome.org/gene/10090:Tex35 ^@ http://purl.uniprot.org/uniprot/Q14BK3 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Testis-specific. Expressed during spermatogenesis. http://togogenome.org/gene/10090:Gdpd4 ^@ http://purl.uniprot.org/uniprot/Q3TT99 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Cytoplasm|||Detected in testis, in particular in spermatocytes.|||Membrane http://togogenome.org/gene/10090:Lrpap1 ^@ http://purl.uniprot.org/uniprot/P55302 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the alpha-2-MRAP family.|||Cell surface|||Endoplasmic reticulum-Golgi intermediate compartment lumen|||Endosome lumen|||Golgi apparatus lumen|||Highly expressed in PYS-2 parietal endoderm cells and in the kidney. The RNA level increased about 10-fold during differentiation of F9 embryonal carcinoma cells to parietal endoderm cells.|||Interacts with the LRP1/alpha-2-macroglobulin receptor heavy and light chains; the interaction is transient and coincides with a reduction of ligand binding by the receptor. Interacts with LRP2/glycoprotein 330. Interacts with LRP1B; binding is followed by internalization and degradation. Interacts with LDLR. Interacts with SORL1 (By similarity). Interacts with LRP1; this interaction is followed by rapid internalization (By similarity).|||Molecular chaperone for LDL receptor-related proteins that may regulate their ligand binding activity along the secretory pathway.|||N-glycosylated.|||Rough endoplasmic reticulum lumen|||cis-Golgi network http://togogenome.org/gene/10090:Cd93 ^@ http://purl.uniprot.org/uniprot/O89103 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in lung, heart and bone marrow. Expressed at lower level in ovary, whole embryo and fetal liver. Not detected in brain, adult liver or thymus. Highly expressed in peritoneal cavity and bone marrow macrophages. Not detected in epithelial cells.|||First detectable in day 9 embryos, in the endocardium and vascular endothelium in the anterior part of the embryo. Expression in endothelial cells, initially restricted to aorta, omphalomesenteric and umbilical arteries, later extends to subcardinal veins, intersomitic arteries and perineural vessels. On day 10, detectable in the entire embryo.|||Interacts with C1QBP; the association may represent a cell surface C1q receptor.|||Membrane|||N- and O-glycosylated.|||Receptor (or element of a larger receptor complex) for C1q, mannose-binding lectin (MBL2) and pulmonary surfactant protein A (SPA). May mediate the enhancement of phagocytosis in monocytes and macrophages upon interaction with soluble defense collagens. May play a role in intercellular adhesion. Marker for early multipotent hematopoietic precursor cells. May play a role in cell-cell interactions during hematopoietic and vascular development. http://togogenome.org/gene/10090:Adam1a ^@ http://purl.uniprot.org/uniprot/Q3V0H1|||http://purl.uniprot.org/uniprot/Q60813 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expression is low at 20, 22 and 24 days after birth but has increased by day 60.|||Heterodimer with ADAM2/fertilin subunit beta.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be involved in sperm-egg fusion.|||Membrane|||Testis. http://togogenome.org/gene/10090:Bora ^@ http://purl.uniprot.org/uniprot/Q8BS90 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the BORA family.|||Interacts with AURKA.|||Phosphorylated by AURKA.|||Required for the activation of AURKA at the onset of mitosis. http://togogenome.org/gene/10090:Or13d1 ^@ http://purl.uniprot.org/uniprot/Q8VFN0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrrfip2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J169|||http://purl.uniprot.org/uniprot/E9QN52|||http://purl.uniprot.org/uniprot/Q91WK0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the LRRFIP family.|||Interacts with DVL3 and FLII (By similarity). Weakly interacts with MYD88 in resting cells. Following LPS-stimulation, the interaction with MYD88 is rapidly enhanced; the complex gradually dissociates to basal levels after 6 hours of stimulation. Interaction with MYD88 is regulated by LPS-induced phosphorylation. In the presence of LPS, competes with FLII for MYD88-binding (By similarity).|||May function as activator of the canonical Wnt signaling pathway, in association with DVL3, upstream of CTNNB1/beta-catenin. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding (By similarity). http://togogenome.org/gene/10090:Utp15 ^@ http://purl.uniprot.org/uniprot/Q8C7V3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. May be a component of the proposed t-UTP subcomplex of the ribosomal small subunit (SSU) processome containing at least UTP4, WDR43, HEATR1, UTP15, WDR75. Interacts directly with UTP4 and WDR43.|||Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Tekt5 ^@ http://purl.uniprot.org/uniprot/G5E8A8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tektin family.|||In germ cells, has highest expression levels during late spermiogenesis (in round spermatids and condensing spermatids).|||Interacts with TEKT3.|||May be a structural component of the sperm flagellum.|||Strongly expressed in germ cells of the testis (at protein level) (PubMed:20378928). Expressed in spermatozoa (PubMed:36708031). Also detected in brain (PubMed:20378928).|||flagellum http://togogenome.org/gene/10090:Cyp2d11 ^@ http://purl.uniprot.org/uniprot/P24457 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Tpbgl ^@ http://purl.uniprot.org/uniprot/Q8C013 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Adra2c ^@ http://purl.uniprot.org/uniprot/Q01337 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.|||Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2C sub-subfamily.|||Cell membrane http://togogenome.org/gene/10090:Amdhd1 ^@ http://purl.uniprot.org/uniprot/Q9DBA8 ^@ Cofactor|||Similarity ^@ Belongs to the metallo-dependent hydrolases superfamily. HutI family.|||Binds 1 zinc or iron ion per subunit. http://togogenome.org/gene/10090:Isoc2a ^@ http://purl.uniprot.org/uniprot/B2RY90|||http://purl.uniprot.org/uniprot/P85094 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the isochorismatase family.|||Cytoplasm|||Interacts with CDKN2A.|||Nucleus|||Ubiquitous. Expressed predominantly in uterus, stomach and urinary tract. http://togogenome.org/gene/10090:Crx ^@ http://purl.uniprot.org/uniprot/A0A0A0MQN6|||http://purl.uniprot.org/uniprot/O54751|||http://purl.uniprot.org/uniprot/Q543C9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 17.5 dpc, expressed in a narrow zone in the peripheral outer nuclear layer of the retina. At P12, expressed over the entire photoreceptor layer.|||Belongs to the paired homeobox family.|||Interacts (via the homeobox) with NRL (via the leucine-zipper domain). Interacts with PDC, RAX2, RORB and SCA7.|||Nucleus|||Retina.|||Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors. http://togogenome.org/gene/10090:Tmco3 ^@ http://purl.uniprot.org/uniprot/Q8BH01 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the monovalent cation:proton antiporter 2 (CPA2) transporter (TC 2.A.37) family.|||Membrane|||Probable Na(+)/H(+) antiporter. http://togogenome.org/gene/10090:Or4c35 ^@ http://purl.uniprot.org/uniprot/Q8VGN9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Enpp4 ^@ http://purl.uniprot.org/uniprot/Q8BTJ4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors (By similarity). http://togogenome.org/gene/10090:Scgb3a2 ^@ http://purl.uniprot.org/uniprot/Q920H1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the secretoglobin family. UGRP subfamily.|||Detected in the pituitary gland from postnatal day 1 onwards (at protein level) (PubMed:24514953). Weakly expressed in embryonic lung at stages 11.5 dpc and 12.5 dpc (PubMed:11682631, PubMed:18535256). Seems to localize most strongly to the growing tips of bronchi at stage 13.5 dpc (PubMed:18535256). Highly expressed in developing lung at stages 16.5 dpc and 18.5 dpc, where it localizes to airway epithelia (PubMed:11682631, PubMed:12406855, PubMed:12175512, PubMed:24514953). During gestation, detected in the mammary gland at 6.5 days post coitum (dpc), but expression declines at 8.5 dpc and is absent at later stages (PubMed:12175512).|||Highly expressed in lung where it localizes to epithelial cells of the trachea, bronchus and bronchioles (at protein level) (PubMed:11682631, PubMed:12406855, PubMed:12175512, PubMed:25242865). Expressed in club cells of the bronchioles (PubMed:12406855). Also detected in the anterior and posterior lobes of the pituitary gland where it may localize to gonadotropic cells (at protein level) (PubMed:24514953). Not detected in other tissues tested (PubMed:11682631, PubMed:12175512).|||Homodimer; disulfide-linked (PubMed:11682631, PubMed:24213919). Monomer (PubMed:11682631, PubMed:24213919). Interacts with APOA1 (By similarity).|||Major isoform.|||Secreted|||Secreted cytokine-like protein (By similarity). Binds to the scavenger receptor MARCO (By similarity). Can also bind to pathogens including the Gram-positive bacterium L.monocytogenes, the Gram-negative bacterium P.aeruginosa, and yeast (By similarity). Strongly inhibits phospholipase A2 (PLA2G1B) activity (PubMed:24213919). Seems to have anti-inflammatory effects in respiratory epithelium (PubMed:16456148, PubMed:25242865). Also has anti-fibrotic activity in lung (PubMed:24213919, PubMed:26559674). May play a role in fetal lung development and maturation (PubMed:18535256). Promotes branching morphogenesis during early stages of lung development (PubMed:18535256). In the pituitary, may inhibit production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (PubMed:24514953).|||Viable and fertile, with no gross abnormalities. Lung tissue appears normal (PubMed:25242865). In a C57BL/6NCr strain background, animals show a mild increase in ovalbumin-induced inflammatory response in lung (PubMed:25242865). However, in a mixed genetic background, there is a reduced ovalbumin-induced inflammatory response, possibly due to the presence of modifier genes (PubMed:25242865). Animals have a more severe response to bleomycin-induced pulmonary fibrosis characterized by increased weight loss, more extensive fibrosis in lung tissue, increased expression of collagen genes, higher numbers of lymphocyte, monocyte and neutrophil cells in bronchoalveolar lavage fluid, and increased cytokine levels (PubMed:26559674). http://togogenome.org/gene/10090:Hmgcs2 ^@ http://purl.uniprot.org/uniprot/P54869 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-427 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the thiolase-like superfamily. HMG-CoA synthase family.|||Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate.|||Homodimer.|||Liver and kidney.|||Mitochondrion|||Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-83 and Lys-310, inhibits the enzymatic activity. http://togogenome.org/gene/10090:Tnks ^@ http://purl.uniprot.org/uniprot/Q6PFX9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.|||Belongs to the ARTD/PARP family.|||Cytoplasm|||Golgi apparatus membrane|||Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2. Interacts with AXIN1. Interacts with AXIN2. Interacts with BLZF1 and CASC3. Interacts with NUMA1.|||Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis.|||Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1. Stimulates 26S proteasome activity.|||Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation.|||centrosome|||nuclear pore complex|||spindle pole|||telomere http://togogenome.org/gene/10090:Fgf21 ^@ http://purl.uniprot.org/uniprot/A0A7U3L6A3|||http://purl.uniprot.org/uniprot/Q9JJN1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||In the liver, down-regulated in postprandial conditions (PubMed:30389664). Up-regulated at the transcriptional level by CREB3L3 (PubMed:30389664).|||Interacts (via C-terminus) with KLB; this interaction is direct. Interacts with FGFR4 (By similarity).|||Most abundantly expressed in the liver, also expressed in the thymus at lower levels (PubMed:10858549, PubMed:30389664). Expressed in skeletal muscle (at protein level). Secreted in plasma (at protein level) (PubMed:30605666).|||Secreted|||Stimulates glucose uptake in differentiated adipocytes via the induction of glucose transporter SLC2A1/GLUT1 expression (but not SLC2A4/GLUT4 expression). Activity probably requires the presence of KLB. Regulates systemic glucose homeostasis and insulin sensitivity. http://togogenome.org/gene/10090:Slit3 ^@ http://purl.uniprot.org/uniprot/B2RX06|||http://purl.uniprot.org/uniprot/Q3UHN1|||http://purl.uniprot.org/uniprot/Q9WVB4|||http://purl.uniprot.org/uniprot/Q9Z0Y6 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation ^@ Detected as early as 8.25 dpc in the ventral neural tube. From 9.5 dpc to 11.5 dpc is expressed in the floor plate and motor columns. This pattern of expression continued until at least 17.5 dpc and remained weak. Rostrally, at 8.25 dpc is expressed in the ventral midline of the neural groove and in the neural fold prior to closure of the neural tube. Between 8.5 dpc and 9.5 dpc, expression is observed in the ventral side of the mesencephalon and metencephalon and in the commissural plate after closure of the neural tube. After 13.5 dpc, the expression of SLIT3 is weak in the developing CNS. At 9.5 dpc, SLIT3 is detected in the otic vesicle and in the clefts between the first and the second branchial arches. Between 10.5 dpc and 11.5 dpc is prominently expressed in the otic vesicle but decreased in the branchial clefts. From 13.5 dpc to 17.5 dpc, expression is observed in the cochlea, in the pigment layer of the retina, and in the olfactory epithelium. At 13.5 dpc expression is observed in the whisker follicle surrounding the bulb and shaft. In the developing limb is first detected at 10.5 dpc in distal limb bud mesenchyme. At this stage, is also observed in lateral ridge tissue flanking the limb bud. This pattern persisted through 11.5 dpc but unlike with SLIT2, expression is not observed in the inter-limb bud lateral ridge tissue. At 11.5 dpc, expression in both the fore- and the hindlimb is most intense in the distal anterior mesenchyme and in the proximal posterior cleft between the limb bud and the lateral ridge. At 13.5 dpc could be detected in the wrist and weakly in palm and proximal part of the digits excluding the tips of the digits.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May act as molecular guidance cue in cellular migration, and function may be mediated by interaction with roundabout homolog receptors.|||Secreted http://togogenome.org/gene/10090:Tmem202 ^@ http://purl.uniprot.org/uniprot/Q80W35 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dmrtb1 ^@ http://purl.uniprot.org/uniprot/A2A9I7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DMRT family.|||Brain.|||Nucleus http://togogenome.org/gene/10090:C1qtnf5 ^@ http://purl.uniprot.org/uniprot/Q8K479|||http://purl.uniprot.org/uniprot/Q8K480 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Defects in Mfrp are the cause of retinal degeneration 6 (RD6). RD6 is an autosomal recessive degeneration of the photoreceptors causing dysfunction of both rods and cones.|||Expressed in retinal pigment epithelium and ciliary epithelium of the eye.|||Homotrimer (via collagen-like domain). May form higher order oligomers by supercoiling of the trimers (By similarity). May interact with ERFE.|||Interacts with C1QTNF5.|||May play a role in eye development.|||Secreted http://togogenome.org/gene/10090:Sesn1 ^@ http://purl.uniprot.org/uniprot/E9PXR3|||http://purl.uniprot.org/uniprot/P58006|||http://purl.uniprot.org/uniprot/Q497S6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sestrin family.|||Cytoplasm|||Functions as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway through the GATOR complex. In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents TORC1 signaling. Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:25259925). This stress-inducible metabolic regulator may also play a role in protection against oxidative and genotoxic stresses. May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1. Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein. Was originally reported to contribute to oxidative stress resistance by reducing PRDX1. However, this could not be confirmed (By similarity).|||Highly expressed in heart and also detected in liver and skeletal muscles (at protein level).|||Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (By similarity). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). Interacts with KEAP1, RBX1 and SQSTM1; in the SQSTM1-dependent autophagic degradation of KEAP1. May interact with PRDX1 (By similarity).|||Nucleus|||The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.|||The N-terminal domain may have an alkylhydroperoxide reductase activity.|||Triple knockout mice lacking Sesn1, Sesn2 and Sesn3 do not display an embryonic lethal phenotype since they are born at an expected Mendelian ratio. Moreover, they are not distinguishable from their wild-type littermates. However, their survival at 10 days is dramatically affected. This is associated with a constitutive activation of TORC1 signaling in the liver, heart and skeletal muscle during postnatal fasting, that occurs between birth and suckling. http://togogenome.org/gene/10090:Csrnp1 ^@ http://purl.uniprot.org/uniprot/P59054 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AXUD1 family.|||Binds to the consensus sequence 5'-AGAGTG-3' and has transcriptional activator activity. May have a tumor-suppressor function. May play a role in apoptosis.|||By interleukin-2.|||Mice display no obvious defects in development, hematopoiesis or T-cell function. Deletion of Csrnp1, Csrnp2 and Csrnp3 together causes partial neonatal lethality, suggesting that they have redundant functions.|||Nucleus|||Widely expressed with highest levels in thymus and lung. Low levels detected in naive T-cells. http://togogenome.org/gene/10090:Bpnt1 ^@ http://purl.uniprot.org/uniprot/A0A1B0GRV0|||http://purl.uniprot.org/uniprot/D3Z0E6|||http://purl.uniprot.org/uniprot/Q9Z0S1 ^@ Activity Regulation|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the inositol monophosphatase superfamily.|||Converts adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to adenosine 5'-phosphosulfate (APS) and 3'(2')-phosphoadenosine 5'- phosphate (PAP) to AMP. Has 1000-fold lower activity towards inositol 1,4-bisphosphate (Ins(1,4)P2) and inositol 1,3,4-trisphosphate (Ins(1,3,4)P3), but does not hydrolyze Ins(1)P, Ins(3,4)P2, Ins(1,3,4,5)P4 or InsP6.|||Uncompetitive inhibition by micromolar concentrations of lithium. Competitive inhibition by inositol 1,4-bisphosphate.|||Widely expressed. Highly expressed in kidney. http://togogenome.org/gene/10090:Armc10 ^@ http://purl.uniprot.org/uniprot/Q9D0L7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with the DNA-binding domain of p53/TP53.|||May play a role in cell survival and cell growth. May suppress the transcriptional activity of p53/TP53 (By similarity).|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Rhbdl2 ^@ http://purl.uniprot.org/uniprot/A2AGA4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S54 family.|||Cell membrane|||Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Known substrate: EFNB3 (By similarity).|||Proteolytic processing of the proenzyme produces an N- and a C-terminal fragment. The processing is required for activation of the protease (By similarity). http://togogenome.org/gene/10090:Npnt ^@ http://purl.uniprot.org/uniprot/D3YTX1|||http://purl.uniprot.org/uniprot/Q3TYB4|||http://purl.uniprot.org/uniprot/Q91V88 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nephronectin family.|||Expressed from 10.5 dpc onward mainly at epithelial-mesenchymal interfaces in kidney and other tissues undergoing morphogenesis (at protein level).|||Expressed in kidney (at protein level).|||Functional ligand of integrin alpha-8/beta-1 in kidney development. Regulates the expression of GDNF with integrin alpha-8/beta-1 which is essential for kidney development. May also play a role in the development and function of various tissues, regulating cell adhesion, spreading and survival through the binding of several integrins.|||Homodimer and homotrimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice display renal agenesis at birth due to a developmental delay. This delay is associated with a reduced expression of Gdnf and is similar to the one found in mice lacking Itga8.|||The MAM domain is required for localization at the cell surface.|||Was named nephronectin based on its potential role in kidney development.|||extracellular matrix http://togogenome.org/gene/10090:Gabra4 ^@ http://purl.uniprot.org/uniprot/Q543Z0|||http://purl.uniprot.org/uniprot/Q9D6F4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA4 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Cntd1 ^@ http://purl.uniprot.org/uniprot/Q9D995 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Cytoplasm|||Homozygous knockout mice for CNTD1 are grossly similar to wild-type, surviving into adulthood and exhibiting appropriate mating behavior. Males are sterile with a decreased testis size. Females are also sterile.|||Interacts with PRR19; this interaction promotes crossover formation (PubMed:32555348). Interacts with RFC3 and RFC4; these interactions facilitate crossover formation (PubMed:32640224). Interacts with CDC34; this interaction regulates the cell-cycle progression (PubMed:32640224).|||Isoform 2 is expressed in spermatocyte.|||Nucleus|||Plays a role in the different steps of crossover formation during meiotic recombination (PubMed:24891606, PubMed:32640224, PubMed:32555348). Participates in the crossover differentiation step of crossover-specific recombination intermediates through its interaction with PRR19 (PubMed:32555348). In addition, stimulates crossover formation through the interactions with RFC3 and RFC4 and simultaneously regulates cell-cycle progression through interactions with CDC34 and subsequent ubiquitination of WEE1 (PubMed:32640224). May also participates in an active deselection process that destabilizes or removes excess pre-CO intermediates (PubMed:24891606).|||Probable cloning artifact. http://togogenome.org/gene/10090:Entpd8 ^@ http://purl.uniprot.org/uniprot/Q8K0L2 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GDA1/CD39 NTPase family.|||Ca(2+) or Mg(2+). Has lower efficiency with Mg(2+).|||Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity. Ectonucleoside NTPDases catalyze the hydrolysis of gamma- and beta-phosphate residues of nucleotides, playing a central role in concentration of extracellular nucleotides. Has activity toward ATP, ADP, UTP and UDP, but not toward AMP.|||Cell membrane|||Expressed in liver, jejunum and kidney.|||N-glycosylated.|||The transmembranous domains are involved in regulation of enzyme activity. http://togogenome.org/gene/10090:Aarsd1 ^@ http://purl.uniprot.org/uniprot/Q3THG9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Functions in trans to edit the amino acid moiety from incorrectly charged Ser-tRNA(Ala). http://togogenome.org/gene/10090:Scgb2b12 ^@ http://purl.uniprot.org/uniprot/S4R2L0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Ccdc106 ^@ http://purl.uniprot.org/uniprot/Q3ULM0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with p53/TP53.|||Nucleus|||Promotes the degradation of p53/TP53 protein and inhibits its transactivity. http://togogenome.org/gene/10090:Astn1 ^@ http://purl.uniprot.org/uniprot/Q61137 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the astrotactin family.|||Cell membrane|||Detected in brain (at protein level) (PubMed:11861479). Expressed specifically in the brain. Expressed in the cerebellum, hippocampus, cerebrum and olfactory bulb (PubMed:8602532).|||Endosome|||First detected in embryonic brain at 12 dpc. Expression increases thereafter, is highest in brain from pups 4 days after birth, and then decreases again. Expression is decreased 14 days after birth, and not detectable in adult brain.|||Interacts with ASTN2; the interaction is not calcium-dependent.|||Neuronal adhesion molecule that is required for normal migration of young postmitotic neuroblasts along glial fibers, especially in the cerebellum. Required for normal rate of migration of granule cells during brain development and for normal cerebellum development.|||Perikaryon|||Slower than normal migration of granule cells in the developing cerebellum, leading to a decreased cerebellum size in adult mice and impaired skills in tasks that require coordinated movement and balance. Granule cells from mutant mice have a rounded shape and lack the elongated shape seen in wild-type. At 6 days after birth, increased granule cell apoptosis is observed, contrary to the situation in wild-type.|||clathrin-coated vesicle http://togogenome.org/gene/10090:Foxl2 ^@ http://purl.uniprot.org/uniprot/O88470|||http://purl.uniprot.org/uniprot/Q2TVT7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the mesenchyme of developing eyelids. Expressed in ovaries throughout development and adulthood, localized to the undifferentiated granulosa cells in small and medium follicles as well as cumulus cells of preovulatory follicles. Expressed in the pituitary.|||Interacts with ESR1. Interacts with UBE2I/UBC9 (By similarity). Interacts with SMAD3. Interacts with DDX20.|||Nucleus|||Sumoylated with SUMO1; sumoylation is required for transcriptional repression activity.|||Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9. Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2. Is a regulator of CYP19 expression. Is a transcriptional repressor of STAR. Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element. http://togogenome.org/gene/10090:Lyn ^@ http://purl.uniprot.org/uniprot/P25911|||http://purl.uniprot.org/uniprot/Q3TCS3|||http://purl.uniprot.org/uniprot/Q3U6Q5|||http://purl.uniprot.org/uniprot/Q8CEI0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated (By similarity). Phosphorylated on tyrosine residues in response to KIT signaling (By similarity). Phosphorylation at Tyr-397 is required for optimal activity (PubMed:16272347). Phosphorylation at Tyr-508 inhibits kinase activity (By similarity). Phosphorylated at Tyr-508 by CSK (By similarity). Dephosphorylated by PTPRC/CD45 (PubMed:10415030). Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A (PubMed:9252121). Phosphorylated in response to ITGB1 in B-cells (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Cytoplasm|||Detected in bone marrow-derived monocytes and macrophages (at protein level) (PubMed:28098138, PubMed:2017160). Expressed predominantly in B-lymphoid and myeloid cells (PubMed:2017160).|||Golgi apparatus|||Interacts with TEC. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC, PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via proline-rich region) (PubMed:28098138). This interaction facilitates the phosphorylation of SCIMP on 'Tyr-96', which enhances binding of SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response to stimulation by lipopolysaccharide in macrophages (PubMed:28098138). Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via ankyrin repeat region) in an activation-independent status of LYN. Forms a multiprotein complex with ANKRD54 and HCLS1. Interacts (via SH2 and SH3 domains) with UNC119; leading to LYN activation (By similarity). Interacts with CD36. Interacts with LYN (PubMed:22496641). Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK (PubMed:12681493). Interacts with BCAR1/CAS and NEDD9/HEF1 (By similarity).|||Membrane|||No visible phenotype at birth. B-cell development in the bone marrow proceeds normally, but mice have reduced numbers of peripheral B-cells, with a greater proportion of immature cells and an increased turnover rate. Dendritic cells also have a more immature phenotype. Mice develop severe asthma upon exposure to airborne antigen. Mice display elevated levels of serum IgM. Aging mice display strongly increased levels of myeloid cells, severe extramedullary hematoipoiesis and tend to develop monocyte/macrophage tumors. After about 16 weeks, mice begin to develop splenomegaly and glomerulonephritis, and display autoimmune antibodies. Their B-cells are hypersensitive to stimulation of the B-cell receptor, and display enhanced activation of the MAP kinase signaling pathway. Mice do not display an allergic response upon IgE receptor engagement.|||Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-96'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (PubMed:28098138). Phosphorylates CLNK (PubMed:12681493). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (By similarity).|||Nucleus|||Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by dasatinib, PP2, and SU6656.|||The protein kinase domain plays an important role in its localization in the cell membrane.|||Ubiquitinated by CBL, leading to its degradation.|||perinuclear region http://togogenome.org/gene/10090:Marveld2 ^@ http://purl.uniprot.org/uniprot/A1BQX3|||http://purl.uniprot.org/uniprot/E9Q1T5|||http://purl.uniprot.org/uniprot/Q3UZP0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELL/occludin family.|||Cell membrane|||Detected in small intestine, stomach and kidney, in epithelial cells (PubMed:16365161). Detected in pancreas, retina and lung, and in stria vascularis, utricle and the organ of Conti in the inner ear (at protein level) (PubMed:26677943, PubMed:17186462). Predominantly detected in small intestine, lung and kidney, with lower levels in liver, testis and brain (PubMed:16365161). In colon, expressed in the entire crypts (PubMed:23239027).|||Interacts with TJP1. Interacts with the ubiquitin ligase ITCH. Interacts (via C-terminal cytoplasmic domain) with LSR (via the cytoplasmic domain), ILDR1 and ILDR2; the interaction is required to recruit MARVELD2 to tricellular contacts (PubMed:21245199, PubMed:23239027).|||Membrane|||No visible phenotype at birth. Mutant mice have normal gait and equilibrium and are fertile. They display severe and rapidly progressing hearing loss already 14 days after birth, and completely lack response to a 90 dB sound 21 days after birth. Endocochlear potential and paracellular permeability in the stria vascularis are not affected. The arrangement of inner and outer hair cells in the organ of Corti appears normal at 12 days after birth, but outer hair cells and inner hair cells have disappeared by 21 days after birth. Hair cells survive on cochlear explants (in vitro), suggesting that hair cell degeneration is due to K(+) leakage from the endolymph to the perilymph.|||Phosphorylated.|||Plays a role in the formation of tricellular tight junctions and of epithelial barriers (PubMed:16365161, PubMed:21245199). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:26677943).|||Ubiquitinated by ITCH; but this ubiquitination does not lead to proteasomal degradation.|||tight junction http://togogenome.org/gene/10090:Mdn1 ^@ http://purl.uniprot.org/uniprot/A2ANY6|||http://purl.uniprot.org/uniprot/J3QMC5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the midasin family.|||Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Il12rb2 ^@ http://purl.uniprot.org/uniprot/D3Z6H5|||http://purl.uniprot.org/uniprot/P97378 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Expressed at high levels in Th1 cells on day 3, 5 and 7 after primary activation. Very low expression in Th2 cells on day 3 and not detectable on day 5 nor day 7 after activation.|||Expressed in developing T-helper (TH) cells.|||Following T-cell activation, expression inhibited by IL4 and induced by IFN gamma.|||Heterodimer/heterooligomer; disulfide-linked. The functional high affinity IL12 receptor is composed of I12RB1 and IL12RB2. Il12RB2 binds JAK2 (via its N-terminal) through a membrane-proximal region of the cytoplasmic domain (By similarity).|||Lps-defective mice C57BL/10ScCr (Cr) mice carry a mutation in the IL12RB2 gene leading to the production of a truncated IL12 receptor beta 2 chain resulting in malfunction of the IL12-mediated IFN-gamma response.|||Membrane|||On IL12 stimulation, phosphorylated on C-terminal tyrosine residues. Phosphorylation of any one of Tyr-757, Tyr-804 or Tyr-811 can activate STAT4, IFN-gamma production, and T-cell proliferation. Tyr-811 is the dominant site of cell proliferation.|||Receptor for interleukin-12. This subunit is the signaling component coupling to the JAK2/STAT4 pathway. Promotes the proliferation of T-cells as well as NK cells. Induces the promotion of T-cells towards the Th1 phenotype by strongly enhancing IFN-gamma production. Can also activate STAT3.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Kif18b ^@ http://purl.uniprot.org/uniprot/Q6PFD6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Cytoplasm|||In complex with KIF2C, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells. Its major role may be to transport KIF2C and/or MAPRE1 along microtubules (By similarity).|||Interacts with MAPRE1; this interaction is required for efficient accumulation at microtubule plus ends. Interacts with KIF2C at microtubule tips; this interaction increases the affinity of both partners for microtubule plus ends and is required for robust microtubule depolymerization. KIF2C phosphorylation by AURKA or AURKB strongly reduces KIF18B-binding.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Ost4 ^@ http://purl.uniprot.org/uniprot/Q99LX8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OST4 family.|||Component of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (By similarity). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity).|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. Specifically involved in maintaining stability of STT3A-containing OST complexes. http://togogenome.org/gene/10090:Dcaf17 ^@ http://purl.uniprot.org/uniprot/Q3TUL7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with DDB1, CUL4A and CUL4B.|||May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.|||Membrane|||Ubiquitously expressed in the embryo, with higher expression in brain, liver and skin tissues.|||nucleolus http://togogenome.org/gene/10090:Med30 ^@ http://purl.uniprot.org/uniprot/Q9CQI9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 30 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Sall4 ^@ http://purl.uniprot.org/uniprot/Q8BX22 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sal C2H2-type zinc-finger protein family.|||Cytoplasm|||Expressed in the embryonic heart (at protein level).|||Interacts with POU5F1/OCT4 (By similarity). Interacts with NANOG (PubMed:16840789). Interacts with BEND3 (By similarity). Interacts with NSD2 (via PHD-type zinc fingers 1, 2 and 3) (PubMed:19483677). Interacts with NRBP1 (PubMed:22510880).|||Nucleus|||Sumoylation with both SUMO1 and SUMO2 regulates the stability, subcellular localization, transcriptional activity, and may reduce interaction with POU5F1/OCT4.|||Transcription factor with a key role in the maintenance and self-renewal of embryonic and hematopoietic stem cells. http://togogenome.org/gene/10090:Pp2d1 ^@ http://purl.uniprot.org/uniprot/Q8BVT6 ^@ Caution|||Similarity ^@ Although it belongs to the protein phosphatase 2C family, it lacks some of the conserved residues that bind manganese, suggesting it has no phosphatase activity.|||Belongs to the PP2C family. http://togogenome.org/gene/10090:Skint9 ^@ http://purl.uniprot.org/uniprot/A7TZG3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin, thymus and testis.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Pbld2 ^@ http://purl.uniprot.org/uniprot/Q9CXN7 ^@ Similarity ^@ Belongs to the PhzF family. http://togogenome.org/gene/10090:Liat1 ^@ http://purl.uniprot.org/uniprot/Q810M6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in spleen, thymus, liver and brown adipose tissue. Moderately expressed in liver, testis and lung.|||LIAT1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas LIAT1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in LIAT1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human LIAT1, respectively.|||Participates in nucleolar liquid-liquid phase separation (LLPS) through its N-terminal intrinsically disordered region (IDR) (PubMed:33443146). May be involved in ATE1-mediated N-terminal arginylation (PubMed:25369936).|||Post-translationally modified by JMJD6 lysyl-hydroxylase activity at its Lys-rich domain, which inhibits its self-association and nucleolar localization.|||Self-associates (via Lys-rich domain); targets LIAT1 to the nucleolus (PubMed:33443146). Interacts with ATE1; it is not a substrate of ATE1, the interaction takes place in the cytoplasm and seems to increase ATE1 arginyltransferase activity (PubMed:25369936, PubMed:33443146). Interacts with JMJD6 and MRPS14 (PubMed:25369936).|||The N-terminal intrinsically disordered region (IDR) facilitates its liquid-liquid phase separation (LLPS) in the nucleolus (PubMed:33443146). In the IDR, the lysine-rich domain mediates self-association and targeting to the nucleolus (PubMed:33443146).|||nucleolus http://togogenome.org/gene/10090:Ino80b ^@ http://purl.uniprot.org/uniprot/Q99PT3 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80 (By similarity). Interacts with RP9.|||Expressed strongly in the testis and moderately in the kidney, skeletal muscle, liver and lung.|||It is uncertain whether Met-1 or Met-18 is the initiator.|||Nucleus|||Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.|||nucleolus http://togogenome.org/gene/10090:Dmap1 ^@ http://purl.uniprot.org/uniprot/Q9JI44 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. DMAP1 also forms a complex with DNMT1 and HDAC2. Throughout S phase it interacts directly with the N-terminus of DNMT1, which serves to recruit DMAP1 to replication foci. DMAP1 interacts with ING1, a component of the mSIN3A transcription repressor complex, although this interaction is not required for recruitment of ING1 to heterochromatin. Interacts directly with the transcriptional corepressor TSG101. Interacts with URI1 (By similarity). Interacts with the pro-apoptotic protein DAXX.|||Cytoplasm|||Involved in transcription repression and activation. Its interaction with HDAC2 may provide a mechanism for histone deacetylation in heterochromatin following replication of DNA at late firing origins. Can also repress transcription independently of histone deacetylase activity. May specifically potentiate DAXX-mediated repression of glucocorticoid receptor-dependent transcription. Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Participates in the nuclear localization of URI1 and increases its transcriptional corepressor activity (By similarity).|||May be due to intron retention.|||Nucleus http://togogenome.org/gene/10090:Mgat2 ^@ http://purl.uniprot.org/uniprot/Q921V5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 16 (GT16) protein family.|||Decreased embryonic survival between 9 and 15 dpc. Surviving embryos are about 20% smaller than their littermates by 15 dpc. Most of the newborn pups die during the first week after birth, and none live longer than 4 weeks. Pups are about half the size of their littermates 8 days after birth, have dismorphic facial features and severe locomotor deficits. Pups display impaired muscle development and defects in bone development including a hunched spinal column, plus poorly calcified and brittle bones in vertebrae, ribs, femur and skull. Mutant mice have also mild anemia and impaired mucus production in the gastrointestinal system. Outcrossing increases the length of the lifespan, but does not increase the number of pups that survive after the fist week. Surviving males display testicular atrophy and are infertile. About one third of the surviving females produce offspring, but do not nurture their pups.|||Detected in liver, lung, testis, kidney, brain, spleen, thymus, uterus and intestine.|||Golgi apparatus membrane|||Homodimer.|||Plays an essential role in protein N-glycosylation. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) onto the free terminal mannose moiety in the core structure of the nascent N-linked glycan chain, giving rise to the second branch in complex glycans. http://togogenome.org/gene/10090:Erbin ^@ http://purl.uniprot.org/uniprot/B2RUJ2|||http://purl.uniprot.org/uniprot/B2RUK2|||http://purl.uniprot.org/uniprot/B7ZNX6|||http://purl.uniprot.org/uniprot/Q80TH2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated ERBB2 'Tyr-1248' receptor, it may contribute to stabilize this unphosphorylated state (By similarity). Inhibits NOD2-dependent NF-kappa-B signaling and pro-inflammatory cytokine secretion (PubMed:16203728).|||Basolateral cell membrane|||Belongs to the LAP (LRR and PDZ) protein family.|||Interacts with ERBB2, BPAG1 and ITGB4. May favor the localization of ERBB2, by restricting its presence to the basolateral membrane of epithelial cells. Also found to interact with ARVCF and delta catenin. Interacts (via C-terminus) with DST (via N-terminus) (By similarity). Interacts with NOD2 (via CARD domain) (PubMed:16203728).|||Isoform 2 is phosphorylated on Ser-1231 and Ser-1234.|||Nucleus membrane|||hemidesmosome http://togogenome.org/gene/10090:Faap20 ^@ http://purl.uniprot.org/uniprot/Q3UN58 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Component of the Fanconi anemia (FA) complex required to recruit the FA complex to DNA interstrand cross-links (ICLs) and promote ICLs repair. Following DNA damage recognizes and binds 'Lys-63'-linked ubiquitin generated by RNF8 at ICLs and recruits other components of the FA complex. Promotes translesion synthesis via interaction with REV1 (By similarity).|||Component of the Fanconi anemia (FA) complex. Interacts with FANCA; interaction is direct. Interacts with REV1 (By similarity).|||Nucleus|||The UBZ2-type zinc finger binds both 'Lys-48'- and 'Lys-63'-linked polyubiquitin with preference for 'Lys-63'-linked polyubiquitin. http://togogenome.org/gene/10090:Vhl ^@ http://purl.uniprot.org/uniprot/P40338|||http://purl.uniprot.org/uniprot/Q3TTE7 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VHL family.|||Cell membrane|||Component of the VBC (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins. Interacts with CUL2; this interaction is dependent on the integrity of the trimeric VBC complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiquitination and degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal. Interacts with ADRB2; the interaction, in normoxia, is dependent on hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically decreased. Interacts with RNF139, USP33 and JADE1 (By similarity). Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with LIMD1 (via LIM zinc-binding 2). Interacts with AJUBA (via LIM domains) and WTIP (via LIM domains) (By similarity). Interacts with EPAS1. Interacts with CARD9 (By similarity). Interacts with DCUN1D1 independently of CUL2; this interaction engages DCUN1D1 in the VCB complex and triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (By similarity). Interacts with ALAS1 (hydroxylated form) (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Expressed throughout fetal nephrogenesis, abdominal and thoracic organogenesis, and nervous system development between day 10.5 and day 16.5. In the developing lung, differential expression within the endodermally derived cuboidal epithelial lining of the terminal and respiratory bronchioles. In the developing eye, high expression in both the inner and outer neuroblastic layers of the retina and lens.|||Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2. Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR.|||Nucleus|||The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]. http://togogenome.org/gene/10090:Pcnx4 ^@ http://purl.uniprot.org/uniprot/E9QN69|||http://purl.uniprot.org/uniprot/Q3UVY5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the pecanex family.|||Membrane http://togogenome.org/gene/10090:Tnfrsf19 ^@ http://purl.uniprot.org/uniprot/Q8BUM7|||http://purl.uniprot.org/uniprot/Q9JLL3 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with TRAF1, TRAF2, TRAF3 and TRAF5. Interacts with LINGO1.|||Can mediate activation of c-Jun and NF-kappa-B. May promote caspase-independent cell death (By similarity). Isoform 2 and isoform 3 may act as decoy receptors.|||Cell membrane|||Highly expressed in adult brain, and in embryos from day 11-17, but not earlier. Detected in embryonic brain and epithelium, and at lower levels in adult heart, lung and liver. In neonatal mice, mainly in hair follicles and neuron-like cells in the cerebellum, but not in the skin epidermis. Isoform 3 was found in embryonic day 17.5 skin but not in brain and liver.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Acoxl ^@ http://purl.uniprot.org/uniprot/Q9DBS4 ^@ Similarity ^@ Belongs to the acyl-CoA oxidase family. http://togogenome.org/gene/10090:Yars2 ^@ http://purl.uniprot.org/uniprot/Q8BJJ2|||http://purl.uniprot.org/uniprot/Q8BYL4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr).|||Homodimer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Psma8 ^@ http://purl.uniprot.org/uniprot/B7ZMS3|||http://purl.uniprot.org/uniprot/Q9CWH6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase T1A family.|||Component of the outer alpha-ring of the 20S proteasome core which is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure (PubMed:23706739, PubMed:31358751). The catalytic chamber with the active sites is on the inside of the barrel (Probable). Interacts with canonical subunits of the spermatoproteasome, including proteasome activators PSME4 (also called PA200) and PSME3 (also called PA28-gamma) (PubMed:31437213). Interacts with proteasome-interacting proteins chaperones including CCT6B and CCT2, ubiquitin ligases (TRIP12, NEDD4, TRIM36 and RAD18), and ubiquitin specific proteases such as USP9X, USP34, USP5 and USP47 (PubMed:31437213). Interacts with meiotic proteins cyclin dependent kinase CDK1 and the ATPase TRIP13 as well as proteins of the synaptonemal complex SIX6OS1 and SYCE3 (PubMed:31437213).|||Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis (PubMed:23706739, PubMed:31358751, PubMed:31437213). The proteasome is a protein complex that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds (Probable). Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis (PubMed:31358751). Localizes to the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I (PubMed:31437213).|||In testes, expressed in spermatocytes at the pachytene stage (weakly in early pachynema and strongly in late pachynema), and its expression persisted thereafter throughout spermatogenesis.|||Knockout mice were obtained according to the expected Mendelian ratios and showed no obvious phenotypes with respect to viability and development; however males show infertility (PubMed:31358751, PubMed:31437213). PSMA8-null spermatocytes exhibit delayed M-phase entry and are finally arrested at this stage, resulting in male infertility (PubMed:31358751, PubMed:31437213).|||Nucleus|||Predicted to have endopeptidase activity (By similarity). However, as it is located in the outer alpha-ring, it is suggested to lack catalytic activity and preferentially interact with regulatory complexes such as PSME4/PA200. http://togogenome.org/gene/10090:Rimkla ^@ http://purl.uniprot.org/uniprot/Q6PFX8 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RimK family.|||Binds 2 magnesium or manganese ions per subunit.|||Catalyzes the synthesis of N-acetyl-L-aspartyl-L-glutamate (NAAG) and N-acetyl-L-aspartyl-L-glutamyl-L-glutamate.|||Cytoplasm|||Highly expressed in spinal cord and brain.|||N-acetyl-L-aspartyl-L-glutamate (NAAG) is the most abundant dipeptide present in vertebrate central nervous system (CNS). http://togogenome.org/gene/10090:Rasgrp1 ^@ http://purl.uniprot.org/uniprot/Q9Z1S3 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoinhibited. Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state. Regulated by DGKA. Regulated by DGKZ. Regulated by PLC gamma and F-actin polymerization (By similarity).|||Belongs to the RASGRP family.|||Cell membrane|||Detected in spleen and thymus. Expressed by mature thymocytes and to a lower extent by bone marrow-derived mast cells (at protein level). Detected in B-cells and keratinocytes (at protein level).|||Endoplasmic reticulum membrane|||Functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. Regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways (By similarity). Functions in mast cell degranulation and cytokine secretion, regulating FcERI-evoked allergic responses (PubMed:17190838). May also function in differentiation of other cell types. Proto-oncogene, which promotes T-cell lymphomagenesis when its expression is deregulated (PubMed:15829980, PubMed:17210708).|||Golgi apparatus membrane|||Homodimer. Forms a signaling complex with DGKZ and HRAS. Interacts with F-actin. Interacts with SKAP1 (By similarity).|||Mice fail to mount anaphylactic allergic reactions and display chronic T-cell immunodeficiencies. Lag (lymphoproliferation-autoimmunity-glomerulonephritis) mice do not express Rasgrp1 and display a systemic lupus erythematosus-like phenotype.|||The phorbol-ester/DAG-type zinc finger is the principal mediator of the targeting to membranes and is required for functional activation through DAG-binding.|||Two EF-hand domains are present. However, only EF-hand 1 (and not EF-hand 2) binds calcium.|||Up-regulated at the double-negative to double-positive transition during thymocyte development. Down-regulated by 12-O-tetradecanoylphorbol-13-acetate (TPA).|||Was reported that thymocytes isolated from a RasGRP1 mutant mouse strain show a defect in Ras activation following T-cell-receptor (TCR) engagement (PubMed:12932358). However, this paper has been retracted because the data in one figure was falsified by one of the authors (PubMed:22808526). The authors stand by the validity of the other figures, results and interpretation in this paper (PubMed:22808526). Furthermore, evidence supporting function is derived by similarity with the human ortholog, so may be true.|||cytosol http://togogenome.org/gene/10090:Sbk3 ^@ http://purl.uniprot.org/uniprot/P0C5K0 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily. http://togogenome.org/gene/10090:Igf1r ^@ http://purl.uniprot.org/uniprot/E9QNX9|||http://purl.uniprot.org/uniprot/Q3U1L4|||http://purl.uniprot.org/uniprot/Q60751 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by autophosphorylation at Tyr-1163, Tyr-1167 and Tyr-1168 on the kinase activation loop; phosphorylation at all three tyrosine residues is required for optimal kinase activity. Inhibited by MSC1609119A-1, BMS-754807, PQIP, benzimidazole pyridinone, isoquinolinedione, bis-azaindole, 3-cyanoquinoline, 2,4-bis-arylamino-1,3-pyrimidine, pyrrolopyrimidine, pyrrole-5-carboxaldehyde, picropodophyllin (PPP), tyrphostin derivatives. While most inhibitors bind to the ATP binding pocket, MSC1609119A-1 functions as allosteric inhibitor and binds close to the DFG motif and the activation loop (By similarity).|||Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner; Tyr-1167 is predominantly phosphorylated first, followed by phosphorylation of Tyr-1163 and Tyr-1168. While every single phosphorylation increases kinase activity, all three tyrosine residues in the kinase activation loop (Tyr-1163, Tyr-1167 and Tyr-1168) have to be phosphorylated for optimal activity. Can be autophosphorylated at additional tyrosine residues (in vitro). Autophosphorylated is followed by phosphorylation of juxtamembrane tyrosines and C-terminal serines. Phosphorylation of Tyr-981 is required for IRS1- and SHC1-binding (By similarity). Phosphorylation of Ser-1280 by GSK-3beta restrains kinase activity and promotes cell surface expression, it requires a priming phosphorylation at Ser-1284. Dephosphorylated by PTPN1.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Controlled by regulated intramembrane proteolysis (RIP). Undergoes metalloprotease-dependent constitutive ectodomain shedding to produce a membrane-anchored 52 kDa C-Terminal fragment which is further processed by presenilin gamma-secretase to yield an intracellular 50 kDa fragment (By similarity).|||Deficient mice are 45% of the size of wild-type littermates at birth, and die shortly due to severe organ hypoplasia.|||Membrane|||Polyubiquitinated at Lys-1170 and Lys-1173 through both 'Lys-48' and 'Lys-29' linkages, promoting receptor endocytosis and subsequent degradation by the proteasome. Ubiquitination is facilitated by pre-existing phosphorylation (By similarity).|||Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R (By similarity). When present in a hybrid receptor with INSR, binds IGF1 (By similarity).|||Sumoylated with SUMO1.|||Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chain carries the kinase domain. Interacts with PIK3R1 and with the PTB/PID domains of IRS1 and SHC1 in vitro when autophosphorylated on tyrosine residues. Forms a hybrid receptor with INSR, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with ARRB1 and ARRB2. Interacts with GRB10. Interacts with RACK1. Interacts with SOCS1, SOCS2 and SOCS3. Interacts with 14-3-3 proteins. Interacts with NMD2. Interacts with MAP3K5. Interacts with STAT3. Found in a ternary complex with IGF1 and ITGAV:ITGB3 or ITGA6:ITGB4 (By similarity). Interacts (nascent precursor form) with ZFAND2B (PubMed:26692333). http://togogenome.org/gene/10090:Nr3c1 ^@ http://purl.uniprot.org/uniprot/P06537 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity.|||Acts as a dominant negative inhibitor of isoform 1 (PubMed:20660300). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (By similarity). Loses this transcription modulator function on its own (By similarity). Has no hormone-binding activity (PubMed:20660300). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (PubMed:20660300). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (By similarity). Directly regulates STAT1 expression in isoform Alpha-independent manner (By similarity).|||Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required.|||Cytoplasm|||Down-regulated by glucocorticoids.|||Expressed at highest level in spleen with lesser amounts in kidney and liver.|||Expressed in spleen, kidney and liver (PubMed:20660300). Expressed in a circadian manner in the liver (PubMed:27686098).|||Has transcriptional activation and repression activity (By similarity). Mediates glucocorticoid-induced apoptosis (By similarity). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (PubMed:21994940).|||Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:9195923, PubMed:21994940). Upon ligand binding FKBP5 dissociates from the complex and FKBP4 takes its place, thereby linking the complex to dynein and mediating transport to the nucleus, where the complex dissociates (PubMed:9195923, PubMed:11278753). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Directly interacts with UNC45A (By similarity). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers (PubMed:9528750). Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (PubMed:9742105). Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (By similarity). Interaction with BAG1 inhibits transactivation (By similarity). Interacts with HEXIM1 and TGFB1I1 (PubMed:10848625). Interacts with NCOA1 (By similarity). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (PubMed:22170608, PubMed:28751364). Interacts with CIART (PubMed:24736997). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with GRIP1 (By similarity). Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (By similarity). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (By similarity). Interacts with GSK3B (By similarity). Interacts with FNIP1 and FNIP2 (By similarity). Interacts (via C-terminus) with HNRNPU (via C-terminus) (By similarity). Interacts with MCM3AP (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (PubMed:27686098). In the absence of hormonal ligand, interacts with TACC1 (By similarity). Interacts (via NR LBD domain) with ZNF764 (via KRAB domain); the interaction regulates transcription factor activity of NR3C1 by directing its actions toward certain biologic pathways (By similarity).|||Increased proteasome-mediated degradation in response to glucocorticoids.|||Mitochondrion|||Nucleus|||Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoids. Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoid. The Ser-221, Ser-243 and Ser-421-phosphorylated forms are mainly cytoplasmic, and the Ser-229-phosphorylated form is nuclear (By similarity). Phosphorylation at Ser-229 increases transcriptional activity (By similarity). Phosphorylation at Ser-221, Ser-243 and Ser-421 decreases signaling capacity (By similarity). Phosphorylation at Ser-421 may protect from glucocorticoid-induced apoptosis (By similarity). Phosphorylation at Ser-221 and Ser-229 is not required in regulation of chromosome segregation (By similarity). May be dephosphorylated by PPP5C, attenuates NR3C1 action (PubMed:21994940).|||Produced by alternative initiation at Met-28 of isoform 1.|||Produced by alternative initiation at Met-28 of isoform 2.|||Produced by alternative splicing.|||Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:10678832). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (By similarity). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (PubMed:15037546).|||Sumoylation at Lys-294 and Lys-310 negatively regulates its transcriptional activity. Sumoylation at Lys-718 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-294 and Lys-310 is dispensable whereas sumoylation at Lys-718 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWDD3-dependent manner.|||T-cell is a critical cellular target of GR, as immune activation in mice lacking GR resulted in significant mortality. This lethal activation is rescued by PTGS2 inhibition but not steroid administration or cytokine neutralization.|||The poly-Gln region in 78-91 is polymorphic (PubMed:3780669, PubMed:17012242, PubMed:20660300, PubMed:16141072, PubMed:15489334). Polymorphism plays a role in complex mechanisms leading to lower corticosterone response to stress, and may also be associated with decreased locomotive and increased anxiety-type behaviors (PubMed:17012242).|||Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling.|||Up-regulated by glucocorticoids and insulin.|||centrosome|||spindle http://togogenome.org/gene/10090:Or1j10 ^@ http://purl.uniprot.org/uniprot/Q8VGK6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tex37 ^@ http://purl.uniprot.org/uniprot/Q9DAG4 ^@ Disruption Phenotype|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Deficeint mice are fertile and have no detectable defects in the testis/body weight ratio, epididymal sperm count, and testicular and epididymal histology.|||Nucleus|||Only detected after the mouse is 35 days old. Expression increases gradually from day 35 to 6 months, and remains stable after 54 days (PubMed:17091336, PubMed:29563520). Exclusively expressed in the epididymis and testis (PubMed:17091336, PubMed:29563520). http://togogenome.org/gene/10090:Hspe1 ^@ http://purl.uniprot.org/uniprot/Q4KL76|||http://purl.uniprot.org/uniprot/Q64433 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GroES chaperonin family.|||By stress.|||Co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp60, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein.|||Homoheptamer arranged in a ring structure. 2 heptameric Hsp10 rings interact with a Hsp60 tetradecamer in the structure of a back-to-back double heptameric ring to form the symmetrical football complex.|||Mitochondrion matrix http://togogenome.org/gene/10090:Nphs2 ^@ http://purl.uniprot.org/uniprot/C0LL94|||http://purl.uniprot.org/uniprot/Q91X05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the band 7/mec-2 family.|||Interacts with nephrin/NPHS1, KIRRL1 and CD2AP. Interacts with DDN.|||Membrane|||Plays a role in the regulation of glomerular permeability, acting probably as a linker between the plasma membrane and the cytoskeleton. http://togogenome.org/gene/10090:Galnt9 ^@ http://purl.uniprot.org/uniprot/G3X942 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Obox6 ^@ http://purl.uniprot.org/uniprot/G3X9U1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:A3galt2 ^@ http://purl.uniprot.org/uniprot/Q3V1N9 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Golgi stack membrane|||Mice are fertile, develop normally and exhibit no overt behavioral abnormalities. However, compared to heterozygous mice they lack expression of the glycosphingolipid isoglobotrihexosylceramide (iGb3) in the dorsal root ganglion.|||Synthesizes the galactose-alpha(1,3)-galactose group on the glycosphingolipid isoglobotrihexosylceramide or isogloboside 3 (iGb3) by catalyzing the transfer of galactose from UDP-Galactose to its acceptor molecule Gal-beta-1,4-Glc-ceramide. Can also catalyze the addition of galactose to iGb3 itself to form polygalactose structures. Synthesis of iGb3 is the initial step in the formation of the isoglobo-series glycolipid pathway and is the precursor to isogloboside 4 (iGb4) and isoForssman glycolipids. Can glycosylate only lipids and not proteins and is solely responsible for initiating the synthesis of isoglobo-series glycosphingolipids.|||The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis (By similarity).|||Thymus and lung. http://togogenome.org/gene/10090:Myzap ^@ http://purl.uniprot.org/uniprot/Q3UIJ9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MYZAP family.|||Cell junction|||Cell membrane|||Detected in embryonic vasculature at 8 dpc. Detected in endocardium and the primitive ventricle at 9 dpc. First detected in myocardium at 11.5 dpc. Highly expressed in heart and lung at 15.5 dpc and in neonates, wherease expression in vasculature is no longer detectable.|||Detected in heart myocardium and lung.|||I band|||Interacts with DSP, MPRIP and TJP1/ZO1. Interaction with MPRIP inhibits the activation of transcription factor SRF. Interacts with GRIN1. Interacts with DYNLL1 (By similarity).|||Plays a role in cellular signaling via Rho-related GTP-binding proteins and activation of transcription factor SRF. Targets TJP1 to cell junctions (By similarity). In cortical neurons, may play a role in glutaminergic signal transduction through interaction with the NMDA receptor subunit GRIN1 (By similarity).|||Z line|||cytoskeleton http://togogenome.org/gene/10090:Map2k4 ^@ http://purl.uniprot.org/uniprot/P47809|||http://purl.uniprot.org/uniprot/Q543X6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Ser-255 and Thr-259 by MAP kinase kinase kinases (MAP3Ks).|||Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Causes irregular alignment of Purkinje cells in the cerebellum and delayed radial migration in the cortex during brain development. The cardiac-specific deletion prevents pathological cardiac hypertrophy.|||Cytoplasm|||Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.|||Interacts with SPAG9. Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3 (By similarity).|||Nucleus|||Strong expression is detected in most of the central nervous system and in liver and thymus during early stages of development. While expression in nervous system increases over time, expression in fetal liver and thymus gradually decreases as embryogenesis proceeds. High level of expression in the central nervous system persists throughout postnatal development and remained at a stable level in adult brain.|||The D domain (residues 35-50) contains a conserved docking site and is required for the binding to MAPk substrates.|||The DVD domain (residues 362-385) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation (By similarity). http://togogenome.org/gene/10090:Cdadc1 ^@ http://purl.uniprot.org/uniprot/G3UW39|||http://purl.uniprot.org/uniprot/Q8BMD5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytidine and deoxycytidylate deaminase family.|||Catalyzes the deamination of cytidine and deoxycytidine into uridine and deoxyuridine, respectively. May play an important role in testicular development and spermatogenesis.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Siglecg ^@ http://purl.uniprot.org/uniprot/Q80ZE3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) During infection by RNA viruses inhibits RIG-I signaling in macrophages by promoting its CBL-dependent ubiquitination and degradation via PTPN11/SHP-2.|||Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||Cd22/Siglec10 double-deficient mice develop autoimmune disease, which is not observed in single-deficient mice.|||Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Expressed in B cells with high levels in pre-B cells and B1a cells of the peritoneal cavity.|||Interacts with PTPN6/SHP-1 upon phosphorylation. Interacts with NCF1 (PubMed:27548433). Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response. Interacts with HMGB1; the interaction is dependent on CD24 (PubMed:19264983). Associates with membrane IgM on the B cell surface (PubMed:24790146). Interacts with RIGI, CBL and PTPN11 (PubMed:23374343).|||Phosphorylation of Tyr-659 is involved in binding to PTPN6.|||Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid (PubMed:20038598). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, seems to act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules (By similarity). Involved in negative regulation of B-cell antigen receptor signaling and specifically acts on B1 cells to inhibit Ca(2+) signaling, cellular expansion and antibody secretion (PubMed:17572677). The inhibition of B cell activation is dependent on PTPN6/SHP-1 (PubMed:23836061). In association with CD24 may be involved in the selective suppression of the immune response to danger-associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90 (PubMed:19264983). In association with CD24 may regulate the immune repsonse of natural killer (NK) cells (By similarity). Plays a role in the control of autoimmunity (PubMed:20200274). During initiation of adaptive immune responses by CD8-alpha(+) dendritic cells inhibits cross-presentation by impairing the formation of MHC class I-peptide complexes. The function seems to implicate recruitment of PTPN6/SHP-1, which dephosphorylates NCF1 of the NADPH oxidase complex consequently promoting phagosomal acidification (PubMed:27548433). http://togogenome.org/gene/10090:Gpr83 ^@ http://purl.uniprot.org/uniprot/P30731 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By glucocorticoids and cAMP in T-cells.|||Cell membrane|||Deficient mice have normal body weight and glucose tolerance when fed a regular chow diet, but are protected from obesity and glucose intolerance when challenged with a high-fat diet (PubMed:23744028). Knockdown of GPR83 has minimal impact on anxiety-like behaviors in female mice and a decrease in anxiety-related behaviors in male mice. In contrast, a local GPR83 knockdown in the basolateral amygdala leads to more anxiety-related behaviors in female mice (PubMed:34512237).|||G-protein coupled receptor for PEN, a neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N). Acts through a G(i)- and G(q)-alpha-alpha-mediated pathway in response to PEN (PubMed:27117253). Plays a role in food intake and body weight regulation (PubMed:23744028). May contribute to the regulation of anxiety-related behaviors (PubMed:34512237).|||NPY has been reported to be a ligand for GPR83 (By similarity). However, a more recent study found that radiolabeled PEN binding to GPR83 is not affected by NPY concentrations below 1 mM, only very high, non-physiological concentrations causes a partial, displacement of PEN binding (PubMed:27117253).|||Predominantly expressed in the brain, with moderate expression in the hypothalamus (PubMed:23744028). Expressed in the thymus (PubMed:16141072). http://togogenome.org/gene/10090:Abca12 ^@ http://purl.uniprot.org/uniprot/E9Q876 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 18.5 dpc highly expressed in the epidermis, and weakly in the stomach.|||Belongs to the ABC transporter superfamily. ABCA family.|||Expressed in a number of other tissues besides skin, including heart, intestine, stomach, and kidney (PubMed:24293640). Expressed mainly in the granular layer of the skin (PubMed:18632686). Expressed in lung (PubMed:18632686). Expressed in alpha and beta cells of pancreatic islets (PubMed:32072744).|||Golgi apparatus membrane|||Homozygous knockout mice for Abca12 are born with a thickened epidermis and die shortly after birth, as water rapidly evaporates from their skin (PubMed:18957418). In a mouse model for harlequin ichthyosis (HI), homozygous knockout mice are smaller and die within a few hours and their entire body are covered of erythematous skin, making their skin less flexible. The entire skin surface is covered with thick scales and some mice develop skin fissures and eversions of the lips (eclabium). At 18.5 dpc, fetuses develop taut and shiny skin without normal skin folds and show contractures of the limbs. The lungs of the present model mice show signs of alveolar collapse (PubMed:18632686).|||Interacts with NR1H2 and ABCA1; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability.|||Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.|||Transports lipids such as glucosylceramides from the outer to the inner leaflet of lamellar granules (LGs) membrane, whereby the lipids are finally transported to the keratinocyte periphery via the trans-Golgi network and LGs and released to the apical surface of the granular keratinocytes to form lipid lamellae in the stratum corneum of the epidermis, which is essential for skin barrier function (PubMed:18957418, PubMed:27551807, PubMed:24293640, PubMed:20489143, PubMed:18802465). In the meantime, participates in the transport of the lamellar granules-associated proteolytic enzymes, in turn regulates desquamation and keratinocyte differentiation (PubMed:27551807, PubMed:20489143). Furthermore, is essential for the regulation of cellular cholesterol homeostasis by regulating ABCA1-dependent cholesterol efflux from macrophages through interaction with NR1H2 and ABCA1 (PubMed:18802465, PubMed:23931754). Plays pleiotropic roles in regulating glucose stimulated insulin secretion from beta cells, regulating the morphology and fusion of insulin granules, lipid raft abundance and the actin cytoskeleton (PubMed:32072744). Also involved in lung surfactant biogenesis (PubMed:18632686).|||Up-regulated during barrier recovery.|||secretory vesicle membrane http://togogenome.org/gene/10090:Vmn1r40 ^@ http://purl.uniprot.org/uniprot/Q9EQ46 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Asb4 ^@ http://purl.uniprot.org/uniprot/Q9WV71 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Differentially expressed in the vascular lineage during embryonic stem (ES) cell differentiation, with expression increasing when the cells differentiate. At 7.5 dpc, no remarkable expression is detected. At 9.5 dpc, expressed in intersomitic vessels, dorsal aorta, forelimb buds, allantois/umbilical vessels, vitelline vessels, septum transversum, proepicardium, capillary plexi of the head and branchial arches, endocardium, yolk sac vasculature and placenta. At 10.5 dpc, expressed in forelimb and hind limb buds, intersomitic vessels, peripheral liver cells and umbilical vessels, with expression in the capillary plexi of the head and branchial arches no longer detected. At 11.5 dpc, high expression levels are limited to forelimbs and hind limbs and the most caudal intersomitic vessels.|||Highest expression detected in testis, with some expression detected in ovary and heart. Not detected in lung, kidney, liver, spleen and bone marrow.|||Hydroxylation at Asn-246 by HIF1AN may provide an oxygen-dependent regulation mechanism for the function of ASB4 in promoting vascular differentiation.|||Interacts with HIF1AN. Component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex formed of CUL2 or CUL5, Elongin BC (ELOB and ELOC), RBX1 and ASB4.|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes differentiation and maturation of the vascular lineage by an oxygen-dependent mechanism.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Rdh1 ^@ http://purl.uniprot.org/uniprot/Q8CGV4|||http://purl.uniprot.org/uniprot/Q8VIJ7 ^@ Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. http://togogenome.org/gene/10090:Trank1 ^@ http://purl.uniprot.org/uniprot/Q8BV79 ^@ Tissue Specificity ^@ Expressed only in the brain. Detected in the hippocampus, hypothalamus and cingulate gyrus. http://togogenome.org/gene/10090:Vmn1r90 ^@ http://purl.uniprot.org/uniprot/A0A087WR36 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp6v1c1 ^@ http://purl.uniprot.org/uniprot/Q9Z1G3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase C subunit family.|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity (By similarity).|||Ubiquitous. Abundant in brain, liver, kidney and testis.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity).|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Vmn1r55 ^@ http://purl.uniprot.org/uniprot/E9Q8I6 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Tspan7 ^@ http://purl.uniprot.org/uniprot/Q62283 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||May be involved in cell proliferation and cell motility.|||Membrane http://togogenome.org/gene/10090:Nat2 ^@ http://purl.uniprot.org/uniprot/P50295|||http://purl.uniprot.org/uniprot/Q78ZC4 ^@ Function|||Polymorphism|||Similarity|||Subcellular Location Annotation ^@ Belongs to the arylamine N-acetyltransferase family.|||Cytoplasm|||Participates in the detoxification of a plethora of hydrazine and arylamine drugs. 2-aminofluorene and p-aminobenzoic acid (PABA) are preferred substrates for NAT-2. Less activity with anisidine and barely detectable with SMZ.|||There are two forms of NAT2: a rapid/stable isoform (Asn-99) and a slow/unstable isoform (Ile-99). http://togogenome.org/gene/10090:Plcz1 ^@ http://purl.uniprot.org/uniprot/Q8K4D7 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in postpuberal testis, where expression is sperm cell-specific. Also expressed in brain of both sexes.|||Interacts via its C2 domain with PtdIns(3)P and, to a lesser extent, PtdIns(5)P in vitro.|||Nucleus|||The EF-hand and C2 domains are essential for triggering Ca(2+) oscillating activity and the regulation of PLCZ1 enzyme activity.|||The X-Y linker region between PI-PLC X-box and Y-box domains may be a target for proteolysis and may play an important regulatory role during fertilization.|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. In vitro, hydrolyzes PtdIns(4,5)P2 in a Ca(2+)-dependent manner. Triggers intracellular Ca(2+) oscillations in oocytes solely during M phase and is involved in inducing oocyte activation and initiating embryonic development up to the blastocyst stage. Is therefore a strong candidate for the egg-activating soluble sperm factor that is transferred from the sperm into the egg cytoplasm following gamete membrane fusion. May exert an inhibitory effect on phospholipase-C-coupled processes that depend on calcium ions and protein kinase C, including CFTR trafficking and function.|||Transgenic mice, where broad ectopic expression is forced, initially appear healthy and their oocytes undergo unperturbed meiotic maturation to metaphase II but subsequently exhibit autonomous intracellular free calcium oscillations, second polar body extrusion, pronucleus formation and parthenogenetic development. Transgenic males remained largely asymptomatic, whereas transgenic females develop abdominal swellings caused by benign ovarian teratomas.|||perinuclear region http://togogenome.org/gene/10090:Gadl1 ^@ http://purl.uniprot.org/uniprot/A0A8Q0QWL6|||http://purl.uniprot.org/uniprot/Q80WP8 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Activated weakly by 0.2-0.4 mM Li(+). Inhibited by bis-carboxymethyl-trithiocarbonate, ethylxanthogenacetic acid and 2,5-disulfoaniline.|||Belongs to the group II decarboxylase family.|||Catalyzes the decarboxylation of L-aspartate, 3-sulfino-L-alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine, hypotaurine and taurine, respectively. The preferred substrate is L-aspartate. Does not exhibit any decarboxylation activity toward glutamate.|||Expressed in skeletal muscles and kidney (at protein level). Expressed in skeletal muscle and weakly in brain. Not expressed in liver or kidney. Expressed in brain, olfactory bulb, liver, muscle and kidney with the highest expression in olfactory bulb and almost not detected in liver (at protein level) (PubMed:26327310).|||Expression in total brain lysate is weak but seems to decrease with age as detected from 17 dpc to 12 months.|||Homodimer. http://togogenome.org/gene/10090:Crk ^@ http://purl.uniprot.org/uniprot/Q5ND51|||http://purl.uniprot.org/uniprot/Q64010 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRK family.|||Cell membrane|||Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK (By similarity). Within the complex, interacts with SH2D3C (via C-terminus), and BCAR1/CAS (By similarity). Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity). Interacts with ABL1, C3G, DOCK3, DOCK5, MAP4K1, MAPK8 and SOS via its first SH3 domain. Interacts (via SH2 domain) with BCAR1, CBL, CBLB, PXN, IRS4 and GAB1 upon stimulus-induced tyrosine phosphorylation. Interacts (via SH2 domain) with several tyrosine-phosphorylated growth factor receptors such as EGFR and INSR. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with DOCK1 and DOCK4. Interacts with SHB. Interacts with PEAK1. Interacts with FASLG. Interacts with FLT4 (tyrosine-phosphorylated). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and p130cas/BCAR1. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with CBLC (By similarity).|||Cytoplasm|||Interacts (via SH2 domain) with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated) (By similarity). Interacts with EPHA3 (phosphorylated); upon activation of EPHA3 by the ligand EFNA5 and EPHA3 tyrosine kinase activity-dependent and mediates EFNA5-EPHA3 signaling through RHOA GTPase activation (PubMed:11870224). Interacts with KIT (PubMed:12878163). Interacts with PEAK3; the interaction requires PEAK3 homodimerization (By similarity).|||Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1.|||Isoform CRK-II: Regulates cell adhesion, spreading and migration. Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4 (By similarity). May regulate the EFNA5-EPHA3 signaling (PubMed:11870224).|||Phosphorylated on Tyr-221 upon cell adhesion. Results in the negative regulation of the association with SH2- and SH3-binding partners, possibly by the formation of an intramolecular interaction of phosphorylated Tyr-221 with the SH2 domain. This leads finally to the down-regulation of the Crk signaling pathway (PubMed:8194526, PubMed:12878163). Isoform Crk-II: Phosphorylated by KIT (By similarity).|||Proline isomerization at Pro-237 by PPIA acts as a switch between two conformations: an autoinhibitory conformation in the cis form, where the tandem SH3 domains interact intramolecularly, and an activated conformation in the trans form.|||The C-terminal SH3 domain function as a negative modulator for transformation and the N-terminal SH3 domain appears to function as a positive regulator for transformation.|||The SH2 domain mediates interaction with tyrosine phosphorylated proteins. Mediates interaction with SHB.|||Ubiquitous. http://togogenome.org/gene/10090:Mob2 ^@ http://purl.uniprot.org/uniprot/Q8VI63 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MOB1/phocein family.|||Binds STK38 and STK38L.|||Nucleus|||Phosphorylated.|||Stimulates the autophosphorylation and kinase activity of STK38 and STK38L.|||perinuclear region http://togogenome.org/gene/10090:Snx29 ^@ http://purl.uniprot.org/uniprot/Q9D3S3 ^@ Sequence Caution|||Similarity ^@ Belongs to the sorting nexin family.|||Probable cloning artifact. http://togogenome.org/gene/10090:Slc39a2 ^@ http://purl.uniprot.org/uniprot/G3X943 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Deficient mice do not reveal any specific phenotype, however these mice are more susceptible to abnormal embryonic development because of zinc deficiency during pregnancy.|||High expression in the liver, skin and ovary.|||It was previously proposed that SLC39A2 operates as a Zn2(+)/HCO3(-) symport mechanism (By similarity). However in more recent studies, SLC39A2-mediated transport is independent of both HCO3(-) and H(+)-driving forces, but modulated by extracellular pH and voltage (By similarity).|||Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space (PubMed:14525987). The Zn(2+) uniporter activity is independent of H(+)-driving force, but is modulated by extracellular pH and membrane potential. Transports also other divalent cations Zn(2+), Cd2(+), Cu2(+), Co2(+) in the order of decreasing affinity, respectively (By similarity). In the skin, aids in the differentiation of keratinocytes in the epidermis (PubMed:24936057).|||Up-regulated upon the induction of differentiation in cultured keratinocytes. http://togogenome.org/gene/10090:Abcc10 ^@ http://purl.uniprot.org/uniprot/Q8R4P9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent transport of glucuronide conjugates such as estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4). Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (By similarity).|||Basal cell membrane|||Basolateral cell membrane|||Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Cell membrane|||Deficient mice exhibit increased sensitivity to paclitaxel-induced mortality associated with weight loss, decreased white blood cell, and small spleen and thymus cortex due to apoptosis and/or depopulation of lymphoid cells.|||Expressed in all tissues tested including liver, brain, heart, skeletal muscle, kidney and spleen.|||Expressed in embryo. http://togogenome.org/gene/10090:Nlrc3 ^@ http://purl.uniprot.org/uniprot/Q5DU56 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NLRP family.|||Cytoplasm|||Directly interacts (via CARD) with TMEM173/STING; this interaction reduces TMEM173 trafficking to the perinuclear region in response to interferon stimulatory DNA. Also interacts, but to a lesser extent, with TBK1 (PubMed:24560620). Interacts with TRAF6; this interaction results in decreased TRAF6 'Lys-63'-linked polyubiquitination, but leaves 'Lys-48'-linked chains unchanged, promoting TRAF6 protein degradation (By similarity). Interacts with PIK3R1/PIK3R2; this interaction disrupts the association between PIK3R1/PIK3R2 and the p110 catalytic subunit PIK3CA/PIK3CB/PIK3CD and reduces PIK3R1/PIK3R2 activation (PubMed:27951586). Weakly interacts with PYCARD/ASC. Interacts with CASP1 and CASP5 (By similarity).|||Expressed in bone marrow-derived macrophages.|||Negative regulator of the innate immune response. Attenuates signaling pathways activated by Toll-like receptors (TLRs) and the DNA sensor STING/TMEM173 in response to pathogen-associated molecular patterns, such as intracellular poly(dA:dT), but not poly(I:C), or in response to DNA virus infection, including that of Herpes simplex virus 1 (HSV1) (PubMed:22863753, PubMed:24560620). May affect TLR4 signaling by acting at the level of TRAF6 ubiquitination, decreasing the activating 'Lys-63'-linked ubiquitination and leaving unchanged the degradative 'Lys-48'-linked ubiquitination (PubMed:22863753). Inhibits the PI3K-AKT-mTOR pathway possibly by directly interacting with the posphatidylinositol 3-kinase regulatory subunit p85 (PIK3R1/PIK3R2) and disrupting the association between PIK3R1/PIK3R2 and the catalytic subunit p110 (PIK3CA/PIK3CB/PIK3CD) and reducing PIK3R1/PIK3R2 activation. Via its regulation of the PI3K-AKT-mTOR pathway, controls cell proliferation, predominantly in intestinal epithelial cells (PubMed:27951586). May also affect NOD1- or NOD2-mediated NF-kappa-B activation (By similarity). Might also affect the inflammatory response by preventing NLRP3 inflammasome formation, CASP1 cleavage and IL1B maturation (By similarity).|||No visible phenotype under basal conditions (PubMed:22863753). Mutant mice show an enhanced response to lipopolysaccharide (LPS)-induced endotoxic shock (PubMed:22863753). Herpes simplex virus 1-infected knockout mice exhibit enhanced innate immunity and reduced morbidity and viral load compared to wild-type animals (PubMed:24560620). Mutant mice are hyper-susceptible to colitis-associated colorectal tumorigenesis (PubMed:27951586).|||The leucine-rich repeat domain may reduce the interaction with TMEM173/STING. http://togogenome.org/gene/10090:Slc34a3 ^@ http://purl.uniprot.org/uniprot/Q80SU6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC34A transporter family.|||Expressed only in the kidney.|||Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane (PubMed:12690469, PubMed:16113079). The cotransport has a Na(+):Pi stoichiometry of 2:1 and is electroneutral (PubMed:16113079). http://togogenome.org/gene/10090:Khdrbs2 ^@ http://purl.uniprot.org/uniprot/Q9WU01 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the KHDRBS family.|||Expressed in heart, skin, brain, colon, spleen, kidney, cervix and testis. In adult cerebellum expressed predominantly in Purkinje cells and in the hippocampus is abundantly expressed in glutamatergic dentate granule cells and in specific inhibitory Schaffer collateral-associated and path-associated interneurons; expression is restricted to neuronal subpopulations largely non-overlapping with expression of KHDRBS3/SLM-2 (at protein level).|||In the developing cerebellum expression is increasing in the first 3 postnatal weeks.|||Methylated.|||Nucleus|||RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion (By similarity). Binds both poly(A) and poly(U) homopolymers. Phosphorylation by PTK6 inhibits its RNA-binding ability. Induces an increased concentration-dependent incorporation of exon in CD44 pre-mRNA by direct binding to purine-rich exonic enhancer (By similarity). Can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners. Regulates cell-type specific alternative splicing of NRXN1 at AS4 and acts synergystically with SAM68 in exon skipping. In contrast acts antagonistically with SAM68 in NRXN3 exon skipping at AS4 (PubMed:22196734, PubMed:24469635). Its phosphorylation by FYN inhibits its ability to regulate splice site selection (By similarity). May function as an adapter protein for Src kinases during mitosis (PubMed:10077576).|||Self-associates to form homooligomers (By similarity). Interacts with KHDRBS1/SAM68; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity (PubMed:10077576). Interacts with RBMX, SAFB, SFRS9 and YTHDC1 (By similarity). Interacts with FYN and PLCG1 (via SH3 domain). Interacts (phosphorylated) with FYN, GRB2, PLCG1 and RASA1 (via SH2 domain) (PubMed:10077576).|||Tyrosine phosphorylated by FYN, PTK6 and SRC. Tyrosine phosphorylated by SRC during mitosis. http://togogenome.org/gene/10090:Iba57 ^@ http://purl.uniprot.org/uniprot/Q8CAK1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GcvT family. CAF17 subfamily.|||Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway.|||Mitochondrion http://togogenome.org/gene/10090:Or13j1 ^@ http://purl.uniprot.org/uniprot/Q9QZ18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Matcap2 ^@ http://purl.uniprot.org/uniprot/Q7TQE7 ^@ Cofactor|||Domain|||Function ^@ Binds 1 zinc ion per subunit.|||Putative metalloprotease with an atypical HExxxH zinc-binding motif instead of HExxH, which interrupts the active site-containing helix without affecting the integrity of the catalytic site arrangement.|||Putative tyrosine carboxypeptidase. http://togogenome.org/gene/10090:Hrh1 ^@ http://purl.uniprot.org/uniprot/B3Y5T0|||http://purl.uniprot.org/uniprot/P70174 ^@ Function|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system. Involved in circadian rhythm of locomotor activity and exploratory behavior. Also involved in responsiveness to pertussis toxin through its control of susceptibility to histamine hypersensitivity and enhancement of antigen-specific delayed-type hypersensitivity responses.|||Membrane|||Phosphorylation at sites in the second and third cytoplasmic loops independently contribute to agonist-induced receptor down-regulation.|||Strains C3H/HeJ and CBA/J are resistant to vasoactive amine sensitization elicited by histamine (VAASH) which is induced by pertussis toxin. http://togogenome.org/gene/10090:Htra3 ^@ http://purl.uniprot.org/uniprot/Q9D236 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1C family.|||First expressed at 9.5 dpc. Levels then increase until 14.5 dpc after which they remain high until newborn. First detected in the eye at 10.5 dpc and then expressed in tissues associated with skeletal tissue. At 12.5 dpc expressed in the vertebral rudiments in the tail region and, in the developing eye, in lens epithelium. At adulthood, expression found in the ganglion cell layer and the inner nuclear layer of the retina. In the developing heart at 16.5 dpc, expressed in the endocardial cushion. In the trachea at this stage, in outer layers and in the aorta, in adventitia.|||Highest level of isoform 1 in maternal part of the placenta, moderate level in heart, testis and ovary, low level in muscle and lung. High expression found in granulosa cells of the ovary. Expressed in bone matrix, particularly in articular chondrocytes. Very low level of isoform 2 expressed in placenta. Expressed in the bone matrix, particularly in articular chondrocytes.|||Homotrimer (By similarity). Interacts with MYH9 (By similarity). Interacts with TGFB1; the interaction inhibits TGFB-mediated signaling. Interacts with BMP4; the interaction inhibits BMP4-mediated signaling. Interacts with TGFB2 and GDF5.|||Secreted|||Serine protease that cleaves beta-casein/CSN2 as well as several extracellular matrix (ECM) proteoglycans such as decorin/DCN, biglycan/BGN and fibronectin/FN1. Inhibits signaling mediated by TGF-beta family proteins possibly indirectly by degradation of these ECM proteoglycans (PubMed:15206957). May act as a tumor suppressor. Negatively regulates, in vitro, trophoblast invasion during placental development and may be involved in the development of the placenta in vivo. May also have a role in ovarian development, granulosa cell differentiation and luteinization (By similarity).|||Up-regulated during early pregnancy coinciding with placentation. Also up-regulated in joint cartilage affected by arthritis. http://togogenome.org/gene/10090:Cryl1 ^@ http://purl.uniprot.org/uniprot/A7VMV2|||http://purl.uniprot.org/uniprot/Q99KP3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.|||Cytoplasm|||Has high L-gulonate 3-dehydrogenase activity. It also exhibits low dehydrogenase activity toward L-3-hydroxybutyrate (HBA) and L-threonate.|||Homodimer.|||Inhibited by malonate.|||Widely expressed, with highest levels in liver. Undetectable in skeletal muscle. http://togogenome.org/gene/10090:Nkx2-3 ^@ http://purl.uniprot.org/uniprot/P97334 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NK-2 homeobox family.|||Expressed in gut mesenchyme during pre- and postnatal development. Expressed as well in the pharyngeal floor and pouches, and in the oral and branchial arch ectoderm. Expression persisted in the developing thyroid until birth, in mucous forming cells of salivary glands and in odontogenic epithelium of the mandible.|||Expressed in spleen and intestine. Also expressed in salivary gland and tongue.|||Nucleus|||Transcriptional regulator essential for normal development and functions of the small intestine and spleen. Activates directly MADCAM1 expression. Required for homing of lymphocytes in spleen and mucosa-associated lymphoid tissue. May have a role during pharyngeal organogenesis. http://togogenome.org/gene/10090:AA986860 ^@ http://purl.uniprot.org/uniprot/Q8BI29 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SARG family.|||Cytoplasm|||Putative androgen-specific receptor. http://togogenome.org/gene/10090:Kcne1l ^@ http://purl.uniprot.org/uniprot/Q9QZ26 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel KCNE family.|||Detected in embryonal dorsal root and nerve ganglia, in the somites and in myoepicardial layer of the developing heart wall. Detected at lower levels in the central nervous system (CNS) and in developing limb.|||Interacts with KCNQ1; impairs KCNQ1 localization in lipid rafts and only conducts current upon strong and continued depolarization.|||Membrane|||Potassium channel ancillary subunit that is essential for generation of some native K(+) currents by virtue of formation of heteromeric ion channel complex with voltage-gated potassium (Kv) channel pore-forming alpha subunits. Functions as an inhibitory beta-subunit of the repolarizing cardiac potassium ion channel KCNQ1. http://togogenome.org/gene/10090:Or56b1b ^@ http://purl.uniprot.org/uniprot/Q7TRU7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gca ^@ http://purl.uniprot.org/uniprot/Q8VC88 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Calcium-binding protein that may play a role in the adhesion of neutrophils to fibronectin. May play a role in the formation of focal adhesions.|||Cytoplasm|||Cytoplasmic granule membrane|||Homodimer. Interacts with SRI and LCP1 (By similarity).|||No visible phenotype. Not essential for normal resistance to microbial infections. Grancalcin-deficient neutrophils exhibit decreased adhesion to fibronectin, and a strongly reduced number of focal adhesion complexes.|||This protein has been shown to bind calcium with high affinity. http://togogenome.org/gene/10090:Vmn2r32 ^@ http://purl.uniprot.org/uniprot/K7N686 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem14a ^@ http://purl.uniprot.org/uniprot/D3YV08|||http://purl.uniprot.org/uniprot/P56983|||http://purl.uniprot.org/uniprot/Q9CYF4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM14 family.|||Endoplasmic reticulum membrane|||Inhibits apoptosis via negative regulation of the mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway.|||Mitochondrion membrane http://togogenome.org/gene/10090:Hoxa6 ^@ http://purl.uniprot.org/uniprot/P09092|||http://purl.uniprot.org/uniprot/Q0VEU7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Tub ^@ http://purl.uniprot.org/uniprot/P50586|||http://purl.uniprot.org/uniprot/Q4VA41 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TUB family.|||Cell membrane|||Cytoplasm|||Defects in Tub are the cause of maturity-onset obesity, insulin resistance and sensory deficits.|||Functions in signal transduction from heterotrimeric G protein-coupled receptors. Binds to membranes containing phosphatidylinositol 4,5-bisphosphate. Can bind DNA (in vitro). May contribute to the regulation of transcription in the nucleus. Could be involved in the hypothalamic regulation of body weight. Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages (By similarity).|||Interacts with GNAQ. Interacts with TULP1.|||Nucleus|||Secreted http://togogenome.org/gene/10090:Slc1a6 ^@ http://purl.uniprot.org/uniprot/B2RQX4|||http://purl.uniprot.org/uniprot/O35544|||http://purl.uniprot.org/uniprot/Q3TXM3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.|||Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A6 subfamily.|||Brain specific.|||Cell membrane|||Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.|||Homotrimer.|||Membrane|||Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:9379843). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport (By similarity). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (Probable). http://togogenome.org/gene/10090:Cmtr1 ^@ http://purl.uniprot.org/uniprot/Q9DBC3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with POLR2A (via C-terminus).|||Nucleus|||S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway. http://togogenome.org/gene/10090:Prrg2 ^@ http://purl.uniprot.org/uniprot/Q8R182 ^@ PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.|||Interacts with NEDD4 (PubMed:11042109). Interacts with transcriptional coactivator YAP1 (By similarity). http://togogenome.org/gene/10090:Gpr4 ^@ http://purl.uniprot.org/uniprot/Q8BUD0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice display partial neonatal and postnatal lethality, hemorrhages, impaired association of vascular smooth muscle cells with capillaries and small arteries and veins, and impaired contact between mesangial cells and renal glomerular capillaries (PubMed:17145776). The inflammatory response is reduced in an inflammatory hindlimb ischemia-reperfusion model (PubMed:26068853). Deficient mice display reduced central respiratory chemoreflex, increased apnea frequency, and blunted ventilatory responses to CO2 (PubMed:32058960).|||Detected in neurons of the brain-stem retrotrapezoid nucleus (RTN).|||Proton-sensing G-protein coupled receptor couples to multiple intracellular signaling pathways, including GNAS/cAMP, GNAQ/phospholipase C (PLC), and GNA12/GNA13/Rho pathways (PubMed:17145776). Acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells through the GNA12/GNA13/Rho GTPase signaling pathway (PubMed:32058960). In the brain may mediate central respiratory sensitivity to CO(2)/H(+) (PubMed:26068853). http://togogenome.org/gene/10090:Mark2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B1|||http://purl.uniprot.org/uniprot/A0A0R4J227|||http://purl.uniprot.org/uniprot/E9QMP6|||http://purl.uniprot.org/uniprot/Q05512|||http://purl.uniprot.org/uniprot/Q3T9A3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-208 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-212 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation by CaMK1 promotes activity and is required to promote neurite outgrowth. Phosphorylation at Thr-593 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity and promotes binding to 14-3-3 protein YWHAZ, leading to relocation from cell membrane to cytoplasm (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cell membrane|||Cytoplasm|||Highly expressed in adult kidney and testis, lower levels in heart, brain, spleen, lung and liver. Expressed in the head and neural fold in 8 dpc embryos, the limb buds, telencephalic vesicles, eyes, branchial archs and heart at 11.5 dpc, the ectoderm at 13 dpc and epiderm, hair and whisker follicles at 15 dpc.|||Homodimer. Interacts with PAK5; leading to inhibit the protein kinase activity (By similarity). Interacts with MAPT/TAU. Interacts with MTCL1; the interaction is direct and increases MARK2 microtubule-binding ability. Interacts (when phosphorylated at Thr-593) with YWHAZ (By similarity). Interacts with YWHAB, YWHAG and YWHAQ (By similarity).|||Inhibited by PAK5; inhibition is independent of the kinase activity of PAK5. Activated by phosphorylation on Thr-208. Inhibited by phosphorylation at Ser-212 and Thr-593. Inhibited by hymenialdisine (By similarity).|||Lateral cell membrane|||Mice have no embryonic defect and are viable. They do not display obvious neuronal phenotype, possibly due to genetic redundancy with Mark1, Mark3 and Mark4. They however show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. They also show immune-cell dysfunction. As mice age, they develop splenomegaly, lymphadenopathy, membranoproliferative glomerulonephritis, and lymphocytic infiltrates in the lungs, parotid glands and kidneys. Moreover, mice are lean, insulin hypersensitive, resistant to high-fat-diet-induced weight gain, and hypermetabolic.|||Serine/threonine-protein kinase. Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU. Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells.|||The KA1 domain mediates binding to phospholipids and targeting to membranes.|||The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain (By similarity).|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:H3c7 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Polr2b ^@ http://purl.uniprot.org/uniprot/Q8CFI7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNA polymerase beta chain family.|||Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with WDR82 (By similarity). Interacts with MEN1 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB2 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template (By similarity).|||Nucleus|||The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits (By similarity). http://togogenome.org/gene/10090:Tspan32 ^@ http://purl.uniprot.org/uniprot/Q3U3L6|||http://purl.uniprot.org/uniprot/Q7TNQ7|||http://purl.uniprot.org/uniprot/Q9JHH2 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Expressed exclusively in hematopoietic tissues. Expression detected in spleen, thymus, bone marrow and peripheral blood leukocytes but not in heart, brain, lung, liver, kidney or testis.|||Expressed from early embryogenesis through to adulthood.|||Membrane http://togogenome.org/gene/10090:Tnrc18 ^@ http://purl.uniprot.org/uniprot/Q80WC3 ^@ Caution|||Miscellaneous ^@ Gene prediction inferred by homology with the human sequence. First thought to be the product of 2 distinct genes Tnrc18 and Zfp469.|||Incomplete sequence. http://togogenome.org/gene/10090:Ankrd6 ^@ http://purl.uniprot.org/uniprot/Q69ZU8 ^@ Function|||Subunit ^@ Interacts with AXN1, AXN2 and CSNK1E/CKI-epsilon.|||Recruits CKI-epsilon to the beta-catenin degradation complex that consists of AXN1 or AXN2 and GSK3-beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals. http://togogenome.org/gene/10090:Osbpl8 ^@ http://purl.uniprot.org/uniprot/A0A0R4J150|||http://purl.uniprot.org/uniprot/B9EJ86 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OSBP family.|||Endoplasmic reticulum membrane|||Interacts with SPAG5. Interacts with NUP62.|||Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner. Binds oxysterol, 25-hydroxycholesterol and cholesterol.|||Mice are apparently healthy and show no developmental defects nor gross abnormality of glucose or lipid metabolism. However, they display a significant elevation of plasma HDL cholesterol and phospholipid levels. They also show a modest increase of APOA1, plus a number of mild gender- or diet-specific lipid metabolism phenotypes (PubMed:23554939). Deletion in bone marrow-derived cells, including macrophages, reduces atherosclerotic lesion progression (PubMed:25347070).|||Nucleus membrane|||Widely expressed. Most abundant in liver, spleen, kidney, brain and adipose tissue. http://togogenome.org/gene/10090:Ezh1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1C0|||http://purl.uniprot.org/uniprot/P70351 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. EZ subfamily.|||Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2/EED-EZH1 is less abundant than the PRC2/EED-EZH2 complex, has weak methyltransferase activity and compacts chromatin in the absence of the methyltransferase cofactor S-adenosyl-L-methionine (SAM). Interacts with EZHIP; the interaction blocks EZH1 methyltransferase activity (PubMed:31451685).|||Expressed at high levels in kidney, adrenal gland, testis and brain.|||Nucleus|||Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Required for embryonic stem cell derivation and self-renewal, suggesting that it is involved in safeguarding embryonic stem cell identity. Compared to EZH2-containing complexes, it is less abundant in embryonic stem cells, has weak methyltransferase activity and plays a less critical role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation. http://togogenome.org/gene/10090:Or6f2 ^@ http://purl.uniprot.org/uniprot/Q8VFE7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pidd1 ^@ http://purl.uniprot.org/uniprot/Q9ERV7 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the DNA damage/stress response pathway that functions downstream of p53/TP53 and can either promote cell survival or apoptosis (PubMed:10973264). Associated with CRADD and the CASP2 caspase, it forms the PIDDosome a complex that activates CASP2 and triggers apoptosis. Associated with IKBKG and RIPK1, it enhances sumoylation and ubiquitination of IKBKG which is important for activation of the transcription factor NF-kappa-B (By similarity).|||Cytoplasm|||Forms a complex named the PIDDosome with CASP2 and CRADD (PubMed:22279524). Forms a complex with IKBKG and RIPK1. Interacts with FADD and MADD (By similarity).|||Induced by TP53/tumor suppressor p53 and gamma-irradiation.|||Nucleus|||The Death domain mediates the interaction with CRADD and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn recruit 7 CASP2 to form the PIDDosome.|||The LRR repeat-containing domain has a regulatory activity, being autoinhibitory for the activation of NF-kappa-B.|||Ubiquitous.|||Undergoes autoproteolytic processing whose extent either directs cells towards survival or apoptotic pathways. Autoproteolytically cleaved into two main fragments PIDD-N and PIDD-C. PIDD-C can be further processed into PIDD-CC, a processing which is enhanced by DNA damage. The cleavage producing PIDD-C is required for translocation of PIDD1 to the nucleus upon DNA damage and activation of NF-kappa-B. PIDD-CC mediates the interaction with CRADD and the cleavage producing PIDD-CC is required for the activation of CASP2. PIDD-N remains associated with PIDD-C and PIDD-CC after cleavage. http://togogenome.org/gene/10090:Spink6 ^@ http://purl.uniprot.org/uniprot/Q8BT20 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the upper epidermis and in skin appendages.|||Release of soluble SPINK6 is down-regulated by TNF-alpha. IFN-gamma and retinoic acid. Expression is reduced after mechanical and metabolic injury to the skin barrier.|||Secreted|||Serine protease inhibitor selective for kallikreins. Efficiently inhibits KLK5 and human KLK2, KLK4, KLK5, KLK6, KLK7, KLK12, KLK13 and KLK14. Doesn't inhibit human KLK1 and KLK8. http://togogenome.org/gene/10090:Cacng7 ^@ http://purl.uniprot.org/uniprot/B9EJ14|||http://purl.uniprot.org/uniprot/P62956 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Cell membrane|||Interacts with CACNA1C. Identified in a complex with the L-type calcium channel subunits CACNA1C, CACNA2D1 and either CACNB1 or CACNB2 (By similarity). Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs), such as GRIA1 and GRIA2 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization (By similarity). Shows specificity only for GRIA1 and GRIA2 (By similarity).|||Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Shows specificity only for GRIA1 and GRIA2. http://togogenome.org/gene/10090:Ncor1 ^@ http://purl.uniprot.org/uniprot/Q5PRE9|||http://purl.uniprot.org/uniprot/Q5RIM6|||http://purl.uniprot.org/uniprot/Q8BK32 ^@ Similarity ^@ Belongs to the N-CoR nuclear receptor corepressors family. http://togogenome.org/gene/10090:Or1n1 ^@ http://purl.uniprot.org/uniprot/Q8VGK1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbm28 ^@ http://purl.uniprot.org/uniprot/Q8CGC6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with U1, U2, U4, U5, and U6 spliceosomal small nuclear RNAs (snRNAs).|||Nucleolar component of the spliceosomal ribonucleoprotein complexes.|||nucleolus http://togogenome.org/gene/10090:Supt5 ^@ http://purl.uniprot.org/uniprot/O55201 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPT5 family.|||Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (By similarity).|||Interacts with SUPT4H1 to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of NELFA, NELFB, NELFD and NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. Also interacts with PRMT1/HRMT1L2, HTATSF1/TATSF1, RNGTT/CAP1A, PRMT5/SKB1, SUPT6H, and can interact with PIN1. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin (By similarity). Interacts with MCM3AP (By similarity).|||Methylated by PRMT1/HRMT1L2 and PRMT5/SKB1. Methylation negatively regulates interaction with P-TEFb and RNA polymerase II (By similarity).|||Nucleus|||Phosphorylated by CDK7 and CDK9. Phosphorylation by P-TEFb alleviates transcriptional pausing. Phosphorylation may also stimulate interaction with PIN1. Bulk phosphorylation occurs predominantly in mitosis (By similarity). http://togogenome.org/gene/10090:Plaat1 ^@ http://purl.uniprot.org/uniprot/Q9QZU4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in brain, heart, and skeletal muscle.|||Belongs to the H-rev107 family.|||Cytoplasm|||Exhibits both phospholipase A1/2 and acyltransferase activities (By similarity). Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (PubMed:21880860). Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid (By similarity). Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (By similarity).|||Expressed in skeletal muscle, heart, brain, bone marrow and testis.|||Membrane|||Nucleus http://togogenome.org/gene/10090:Sox30 ^@ http://purl.uniprot.org/uniprot/Q8CGW4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as both a transcriptional activator and repressor (PubMed:29866902, PubMed:29848638). Binds to the DNA sequence 5'-ACAAT-3' and shows a preference for guanine residues surrounding this core motif (PubMed:29866902). Binds to its own promoter and activates its own transcription (PubMed:29866902, PubMed:29848638). Required to activate the expression of postmeiotic genes involved in spermiogenesis (PubMed:29866902, PubMed:29848638). Binds to the promoter region of CTNNB1 and represses its transcription which leads to inhibition of Wnt signaling (PubMed:29739711). Also inhibits Wnt signaling by binding to the CTNNB1 protein, preventing interaction of CTNNB1 with TCF7L2/TCF4 (By similarity).|||Cytoplasm|||Expressed in the lung (at protein level) (PubMed:29739711). Expressed in testes (at protein level) (PubMed:10359848, PubMed:29848638, PubMed:25609838). Expressed in preleptotene spermatocytes, round spermatids, and elongated spermatids in the testis (at protein level) (PubMed:29866902, PubMed:25609838). Expressed in pachytene spermatocytes during stages 3 to 8 of spermatogenesis (at protein level) (PubMed:29866902, PubMed:29848638, PubMed:25609838). Increased expression in diplotene spermatocytes at stage 9-11 and in metaphase spermatocytes or secondary spermatocytes at stage 12 (PubMed:29848638, PubMed:25609838). Expressed in ovaries (PubMed:29848638).|||Expressed in the testes at 13.5 dpc (PubMed:10359848, PubMed:29848638). Also expressed in the mesonephros, metanephros, brain, lung, heart and stomach at 13.5 dpc (PubMed:10359848). Expressed in the testes at 14.5 dpc (PubMed:29848638). Expressed in the ovary at 13.5 and 14.5 dpc (PubMed:29848638). Expressed weakly in the testes at postnatal day 14 (P14), strongly expressed from P21 onwards (PubMed:29866902). Expressed in the nucleus of pachytene spermatocytes in stages 5 to 6 of spermatogenesis (PubMed:29866902). Expressed in round spermatids and increased expression in pachytene spermatocytes in stages 7 to 8 of spermatogenesis (PubMed:29866902). Expressed in the nucleus of diplotene spermatocytes in stages 11 to 12 of spermatogenesis, however expression in the nuclei of spermatids is lost (PubMed:29866902).|||Induced in germline stem cells by retinoic acid.|||Interacts with CTNNB1, competitively inhibiting CTNNB1-TCF7L2/TCF4 interaction.|||Knockout mice are viable, morphologically normal, but males are sterile (PubMed:29866902, PubMed:29848638). Male mice exhibit small testes and epididymis (PubMed:29848638). Multinuclear syncytia present in the seminiferous tubules, with degenerated multi-chromocenter round spermatids and multinucleated giant cells in the epididymis lumen (PubMed:29848638). Increased numbers of apoptotic cells in the testes and epididymis (PubMed:29848638). Increased expression of CTNNB1, MYC, CCND1, and MMP7 in lung cells (PubMed:29739711). Increase in diplotene spermatocytes in the testes, indicative of defects in the later stages of meiosis (PubMed:29866902). Developmental failure of the large nuclear docking acrosome to develop during the cap phase of spermiogenesis (PubMed:29866902, PubMed:29848638). In addition disruption of proacrosomic vesicle translocation during spermatid differentiation results in the absence of elongating spermatids and therefore viable sperm (PubMed:29866902). No effect on transcription or processing of piRNA precursors (PubMed:29866902).|||Nucleus http://togogenome.org/gene/10090:Sptssb ^@ http://purl.uniprot.org/uniprot/Q925E8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPTSS family. SPTSSB subfamily.|||Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity (By similarity). SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides (By similarity).|||Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. Within the SPT complex, SPTSSB stimulates the catalytic activity and plays a role in substrate specificity. SPT complexes with this subunit showing a preference for longer acyl-CoAs. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.|||Endoplasmic reticulum membrane|||Expression is strong in hypogonadal (hpg) mouse prostate, weak in mature castrated mouse prostate and absent in normal intact or androgen-replaced hpg mouse prostates.|||While expression is androgen independent in the hpg mouse prostate, it appears to be androgen-dependent in the kidney and brain of normal intact mouse suggesting tissue specific regulation by androgens. http://togogenome.org/gene/10090:Nsmce2 ^@ http://purl.uniprot.org/uniprot/Q91VT1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NSE2 family.|||Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3.|||E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination. Is not be required for the stability of the complex. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. Acts as an E3 ligase mediating SUMO attachment to various proteins such as SMC6L1 and TSNAX, the shelterin complex subunits TERF1, TERF2, TINF2 and TERF2IP, RAD51AP1, and maybe the cohesin components RAD21 and STAG2. Required for recruitment of telomeres to PML nuclear bodies. Required for sister chromatid cohesion during prometaphase and mitotic progression.|||Nucleus|||PML body|||Sumoylated, possibly via autosumoylation.|||telomere http://togogenome.org/gene/10090:Gnb5 ^@ http://purl.uniprot.org/uniprot/P62881|||http://purl.uniprot.org/uniprot/Q3UG14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat G protein beta family.|||Component of a complex composed of RGS9 (isoform RGS9-1), GNB5 and RGS9BP; within this complex, the presence of GNB5 stabilizes both itself and RGS9 and increases RGS9 GTPase-activating protein (GAP) activity (PubMed:12119397, PubMed:16908407, PubMed:18204463). Interacts with RGS7, forming the RGS7-GNB5 complex; within this complex, the presence of GNB5 increases RGS7 GTPase-activating protein (GAP) activity (PubMed:31311860, PubMed:34793198). Interacts with GPR158; promotes the GTPase activator activity of the RGS7-GNB5 complex in absence of glycine, in contrast GTPase activator activity of the RGS7-GNB5 complex is inhibited in presence of glycine (PubMed:31311860, PubMed:34793198). Interacts with RGS6 (By similarity).|||Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, such as RGS7 and RGS9, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha subunits, thereby promoting their inactivation (By similarity). Increases RGS7 GTPase-activating protein (GAP) activity, thereby regulating mood and cognition (By similarity). Increases RGS9 GTPase-activating protein (GAP) activity, hence contributes to the deactivation of G protein signaling initiated by D(2) dopamine receptors (By similarity). May play an important role in neuronal signaling, including in the parasympathetic, but not sympathetic, control of heart rate (By similarity).|||Isoform 1 is only detected in retina (PubMed:8910430). Isoform 2 is detected in brain (at protein level) (PubMed:8071339). Isoform 2 is detected in brain (PubMed:8071339).|||Membrane http://togogenome.org/gene/10090:Svs3a ^@ http://purl.uniprot.org/uniprot/F2Z472 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Component of the copulatory plug.|||Covalently cross-linked by transglutaminase, which is important for the formation of the gelatinous copulatory plug. Five repeats of Q-X-K-(S/T) in the central region of the protein serve as the transglutaminase substrate site(s).|||First detected at 3 weeks of age. Expression increases through to 6 weeks of age and remains high thereafter.|||Glycosylated.|||Highly expressed in the seminal vesicle where it is detected in luminal epithelium of the mucosa folds, and also in luminal fluid (at protein level). Not detected in other tissues tested.|||May be due to competing acceptor splice site.|||Secreted|||Up-regulated in response to androgens. http://togogenome.org/gene/10090:Nynrin ^@ http://purl.uniprot.org/uniprot/Q5DTZ0 ^@ Miscellaneous|||Subcellular Location Annotation ^@ Membrane|||The gene encoding this protein may have arisen from the fusion of a cellular gene with retroviral sequences prior to the marsupial-eutherian split. Sequence and structural analyses suggest that the integrase catalytic domain is inactive. http://togogenome.org/gene/10090:Plxna1 ^@ http://purl.uniprot.org/uniprot/P70206 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.|||Interacts directly with NRP1 and NRP2. Interacts with FARP2, RND1 and KDR/VEGFR2. Binding of SEMA3A leads to dissociation of FARP2. Interacts with CRMP1, DPYSL2/CRMP2, DPYSL3/CRMP3 and DPYSL4/CRMP4.|||Ubiquitous. http://togogenome.org/gene/10090:Pcsk5 ^@ http://purl.uniprot.org/uniprot/Q04592|||http://purl.uniprot.org/uniprot/Q91VK0 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ AC 1 and AC 2 (clusters of acidic amino acids) contain sorting information. AC 1 directs TGN localization and interacts with the TGN sorting protein PACS-1.|||Belongs to the peptidase S8 family.|||Endomembrane system|||PC5A is expressed in most tissues but is most abundant in the intestine and adrenals. PC5B is expressed in the intestine, adrenals and lung but not in the brain.|||Secreted|||Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive and regulated secretory pathways. Plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and alpha-integrins. May be responsible for the maturation of gastrointestinal peptides. May be involved in the cellular proliferation of adrenal cortex via the activation of growth factors.|||The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum.|||Weakly expressed throughout the embryo, except in the developing nervous system, the ribs and the liver, but markedly up-regulated at discrete sites during development. At 6.5 dpc, prominent expression observed in differentiated decidua. At 7.5 dpc, intense expression in extraembryonic endoderm, amnion and nascent mesoderm. At 8.5 dpc, abundant expression in somites and yolk sac followed by a confinement to dermamyotome compartment. Between 9.5 dpc and 11.5 dpc, abundant expression in AER (thickened ectodermal cells of limb buds). At 12.5 dpc, expression in the limbs is confined to the condensing mesenchyme surrounding the cartilage. At this stage, strong expression also detected in vertebral and facial cartilage primordia and in the muscle of the tongue. At 16.5 dpc, abundant expression in epithelial cells of the intestinal villi. Isoform A is most abundant at all stages but significant levels of isoform B occur at 12.5 dpc. http://togogenome.org/gene/10090:Ankrd13c ^@ http://purl.uniprot.org/uniprot/Q3UX43 ^@ Function|||Subcellular Location Annotation ^@ Acts as a molecular chaperone for G protein-coupled receptors, regulating their biogenesis and exit from the ER.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:4930568D16Rik ^@ http://purl.uniprot.org/uniprot/A2AUQ7 ^@ Cofactor|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Golgi stack membrane|||Synthesizes the galactose-alpha(1,3)-galactose group by catalyzing the transfer of a galactose residue, with an alpha-1,3 linkage, on terminal lactosaminide (Gal-beta-1,4-GlcNAc-R) disaccharide borne by a glycoprotein or a glycolipid.|||The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis (By similarity).|||This gene is not expressed in humans. http://togogenome.org/gene/10090:Vmn1r38 ^@ http://purl.uniprot.org/uniprot/Q8R2E1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Htr2c ^@ http://purl.uniprot.org/uniprot/P34968|||http://purl.uniprot.org/uniprot/Q8BZI5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in brain cortex, hypothalamus, brainstem and arcuate nucleus. Detected in the paraventricular nucleus of the hypothalamus.|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and feeding behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.|||Interacts with MPDZ. Interacts with ARRB2 (By similarity). Interacts with MPP3; this interaction stabilizes the receptor at the plasma membrane and prevents the desensitization of the HTR2C receptor-mediated calcium response (PubMed:16914526).|||Membrane|||N-glycosylated.|||No obvious phenotype at birth, but mutant mice are prone to sudden death from seizures. When fed ad libitum, adult mice display higher body weight and increased adiposity compared to wild-type littermates. No difference in body weight is found when they receive the same amount of food as their wild-type littermates, indicating that the increased body weight is due to altered feeding behavior. Overweight older mice develop insulin resistance and impaired glucose tolerance. Young mice exhibit insulin resistance, but normal glucose tolerance, due to increased insulin levels in the blood. Insulin resistance is reversed when Htr2c expression is restored in pro-opiomelacortin neurons. Mutant mice display impaired activation of pro-opiomelacortin neurons in the paraventricular nucleus of the hypothalamus, leading to decreased release of CRH and corticosterone. Likewise, they exhibit blunted behavorial responses to anxiogenic environments and stress.|||The PDZ domain-binding motif is involved in the interaction with MPDZ. http://togogenome.org/gene/10090:Ubtd1 ^@ http://purl.uniprot.org/uniprot/Q91WB7 ^@ Function|||Subunit ^@ Interacts with UBTD1.|||May be involved in the regulation of cellular senescence through a positive feedback loop with TP53. Is a TP53 downstream target gene that increases the stability of TP53 protein by promoting the ubiquitination and degradation of MDM2. http://togogenome.org/gene/10090:Or9m2 ^@ http://purl.uniprot.org/uniprot/A2BHP7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pno1 ^@ http://purl.uniprot.org/uniprot/Q9CPS7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PNO1 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA.|||nucleolus http://togogenome.org/gene/10090:Piezo2 ^@ http://purl.uniprot.org/uniprot/E9QNW4|||http://purl.uniprot.org/uniprot/Q8CD54|||http://purl.uniprot.org/uniprot/S4R2S0 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIEZO (TC 1.A.75) family.|||Component of a mechanosensitive channel required for rapidly adapting mechanically activated (MA) currents (PubMed:20813920, PubMed:24717433). Required for Merkel-cell mechanotransduction (PubMed:24717433). Plays a major role in light-touch mechanosensation (PubMed:25471886).|||Due to intron retention.|||Expressed in bladder, colon, and lung, but less abundant in kidney or skin (PubMed:20813920). Strong expression is observed in dorsal root ganglia (DRG) sensory neurons (PubMed:20813920). Expressed in a wide range of cutaneous low-threshold mechanoreceptors (LTMRs), including Merkel cells and Meissner's corpuscles (PubMed:24717433, PubMed:25471886).|||Homooligomer, most likely homotetramer. Interacts with STOML3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Perinatal lethality. Conditional knockout in sensory neurons and Merkel cells causes severe defects in light-touch sensation, although detection of pain (nociception) is unaffected.|||Piezo comes from the Greek 'piesi' meaning pressure. http://togogenome.org/gene/10090:Zscan4b ^@ http://purl.uniprot.org/uniprot/E9Q3G0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Psma7 ^@ http://purl.uniprot.org/uniprot/Q3THL2|||http://purl.uniprot.org/uniprot/Q3UIT9|||http://purl.uniprot.org/uniprot/Q542H2|||http://purl.uniprot.org/uniprot/Q9Z2U0 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||Phosphorylation by ABL1 or ABL2 leads to an inhibition of proteasomal activity and cell cycle transition blocks.|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). PSMA7 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly (By similarity). Interacts with HIF1A (By similarity). Interacts with RAB7A (By similarity). Interacts with PRKN (By similarity). Interacts with ABL1 and ABL2 (By similarity). Interacts with EMAP2 (By similarity). Interacts with MAVS (By similarity).|||Up-regulated in liver tumor tissues. http://togogenome.org/gene/10090:Or4c110 ^@ http://purl.uniprot.org/uniprot/A3KGY3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defb1 ^@ http://purl.uniprot.org/uniprot/P56386 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Detected in kidney.|||Has bactericidal activity. May act as a ligand for C-C chemokine receptor CCR6. Positively regulates the sperm motility and bactericidal activity in a CCR6-dependent manner. Binds to CCR6 and triggers Ca2+ mobilization in the sperm which is important for its motility.|||Membrane|||Monomer. Homodimer.|||Secreted http://togogenome.org/gene/10090:Themis2 ^@ http://purl.uniprot.org/uniprot/Q91YX0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the themis family.|||Cytoplasm|||Expressed in both developing and mature B-cells with high expression in immature, follicular and B1 B cells (PubMed:27992403, PubMed:19597499, PubMed:24907343). Also expressed in macrophages and dendritic cells (PubMed:19597499). Down-regulated in splenocytes of mice developing arthritis in a collagen-induced model, not in those of mice failing to develop the disease. Transiently down-regulated in splenocytes of mice infected with influenza virus (PubMed:19597499).|||Homozygous knockout mice for Themis2 are viable and produced at the expected ratio (PubMed:24907343). Mice show normal B cell development, activation, or Ab responses (PubMed:24907343).|||Interacts with VAV1 (PubMed:20644716, PubMed:22732588). Interacts with LAT (PubMed:22732588). Interacts constitutively with GRB2, LYN and PLCG2; these interactions increase the activation of PLCG2 and its downstream pathways following B cell receptor stimulation (PubMed:27992403, PubMed:20644716, PubMed:22732588).|||May constitute a control point in macrophage inflammatory response, promoting LPS-induced TLR4-mediated TNF production (PubMed:20644716). Determines the threshold for activation of B cells by low-affinity and low-avidity ligands via PLCG2 activation and its downstream pathways (PubMed:27992403).|||Nucleus|||Phosphorylation at Tyr-660 is induced by LPS (PubMed:20644716). Phosphorylated by Src kinases (Lck or Fyn) following BCR engagement (PubMed:20644716).|||Up-regulated by pro-inflammatory stimuli, such as IFNG (at protein level). Down-regulated by anti-inflammatory stimuli, such as TGFB1 and dexamethasone (at protein level).|||Up-regulated during the differentiation of bone marrow precursors into macrophages. http://togogenome.org/gene/10090:Nefl ^@ http://purl.uniprot.org/uniprot/P08551 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the sciatic nerve (at protein level).|||Forms homodimers (in vitro) (By similarity). Forms heterodimers with NEFH or NEFM; which can further hetero-oligomerize (in vitro) (By similarity). Forms heterodimers with INA (in vitro) (By similarity). Interacts with ARHGEF28. Interacts with TRIM2.|||NF-L is the most abundant of the three neurofilament proteins and, like the other nonepithelial intermediate filament proteins, it can form homomeric 10-nm filaments.|||Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks (PubMed:22723690).|||O-glycosylated.|||Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization.|||Reduced levels of Nefm, Nefh and Prph in the sciatic nerve and reduced numbers of neurofilaments in sciatic axons.|||The extra mass and high charge density that distinguish the neurofilament proteins from all other intermediate filament proteins are due to the tailpiece extensions. This region may form a charged scaffolding structure suitable for interaction with other neuronal components or ions.|||Ubiquitinated in the presence of TRIM2 and UBE2D1.|||axon|||cytoskeleton http://togogenome.org/gene/10090:Or5p61 ^@ http://purl.uniprot.org/uniprot/A0A140LJF5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pirb ^@ http://purl.uniprot.org/uniprot/P97484 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the leukocyte receptor cluster (LRC) present on chromosome 7.|||Cell membrane|||Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases, including PTPN6/SHP-1, resulting in the dephosphorylation of the downstream protein kinases SYK and BTK.|||Detected in macrophages, splenocytes and B lymphocytes (at protein level). Detected in macrophages, mast cells, splenocytes, peritoneal cells and natural killer cells.|||Interacts with LYN, PTPN6/SHP-1 and PTPN11/SHP-2.|||May act as receptor for class I MHC antigens. Becomes activated upon coligation of LILRB3 and immune receptors, such as FCGR2B and the B-cell receptor. Down-regulates antigen-induced B-cell activation by recruiting phosphatases to its immunoreceptor tyrosine-based inhibitor motifs (ITIM).|||Phosphorylated on tyrosine residues by LYN. Phosphorylation at Tyr-794 and Tyr-824 is important for interaction with PTPN6/SHP-1 and PTPN11/SHP-2. http://togogenome.org/gene/10090:Nkiras2 ^@ http://purl.uniprot.org/uniprot/Q9CR56 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation. May act by blocking phosphorylation of NFKBIB and nuclear localization of p65/RELA NF-kappa-B subunit. It is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB (By similarity).|||Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily.|||Cytoplasm|||In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Ala and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins.|||Interacts with both NF-kappa-B inhibitor alpha (NFKBIA) and beta (NFKBIB) in vitro. However, it probably only interacts with NFKBIB in vivo (By similarity). http://togogenome.org/gene/10090:Rhou ^@ http://purl.uniprot.org/uniprot/Q9EQT3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts upstream of PAK1 to regulate the actin cytoskeleton, adhesion turnover and increase cell migration. Stimulates quiescent cells to reenter the cell cycle. Has no detectable GTPase activity but its high intrinsic guanine nucleotide exchange activity suggests it is constitutively GTP-bound. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity).|||Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Golgi apparatus membrane|||Interacts with PAK3 (By similarity). Interacts with ARHGAP30 in a GTP-independent manner. In its GTP-loaded conformation, interacts with ARHGAP31. Interacts with PTK2B/PYK2 (By similarity).|||Tyrosine phosphorylated by SRC in response to PTK2B/PYK2 activation.|||focal adhesion|||podosome http://togogenome.org/gene/10090:Vps28 ^@ http://purl.uniprot.org/uniprot/A0A2R8VKS6|||http://purl.uniprot.org/uniprot/Q8BMZ7|||http://purl.uniprot.org/uniprot/Q9D1C8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS28 family.|||Cell membrane|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101, VPS37B, VPS37C, MVB12A and MVB12B. Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with VPS36; the interaction mediates the association with the ESCRT-II complex. Interacts with SNF8 and VPS25. Interacts with CEP55 (By similarity).|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I), a regulator of vesicular trafficking process.|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process.|||Late endosome membrane http://togogenome.org/gene/10090:Ccdc117 ^@ http://purl.uniprot.org/uniprot/Q6PB51 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Facilitates DNA repair, cell cycle progression, and cell proliferation through its interaction with CIAO2B.|||Firstly detected at 8.5 dpc in pharyngeal arch regions, particularly in the first arch, and in developing outflow tract (OFT) regions. Expression continued through 9.5 dpc in the cardiac outflow tract and atria, and in second heart field (SHF)-containing pharyngeal arch with additional expression in lower craniofacial regions. Also expressed in the developing outflow tract and SHF-associated pharyngeal mesoderm, with additional expression observed in pharyngeal endoderm, outflow tract endocardium and ventral neural tube populations.|||Interacts with CIAO2B; the interaction is direct. Interacts with MMS19; the interaction is indirect.|||Nucleus|||spindle http://togogenome.org/gene/10090:Etv2 ^@ http://purl.uniprot.org/uniprot/P41163|||http://purl.uniprot.org/uniprot/Q5EP41 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ETS family.|||Binds to DNA sequences containing the consensus pentanucleotide 5'-CGGA[AT]-3'.|||Nucleus|||Testis. http://togogenome.org/gene/10090:Helq ^@ http://purl.uniprot.org/uniprot/Q2VPA6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. SKI2 subfamily.|||Chromosome|||Hexamer (By similarity). Interacts with POLN (By similarity). Interacts with RAD51B (By similarity). Interacts with RAD51C; promoting association with the BCDX2 complex (PubMed:24005329). Interacts with the replication protein A (RPA/RP-A) complex (By similarity). Interacts with RAD51; stimulating HELQ DNA helicase activity and ability to unwing DNA (By similarity).|||Mice display Fanconi anemia-like phenotypes, characterized by subfertility, germ cell attrition, interstrand cross-links (ICLs) sensitivity and cancer susceptibility.|||Nucleus|||Single-stranded 3'-5' DNA helicase that plays a key role in homology-driven double-strand break (DSB) repair (PubMed:24005329, PubMed:24005041). Involved in different DSB repair mechanisms that are guided by annealing of extensive stretches of complementary bases at break ends, such as microhomology-mediated end-joining (MMEJ), single-strand annealing (SSA) or synthesis-dependent strand annealing (SDSA) (By similarity). Possesses both DNA unwinding and annealing activities (By similarity). Forms a complex with RAD51, stimulating HELQ DNA helicase activity and ability to unwing DNA (By similarity). Efficiently unwinds substrates containing 3' overhangs or a D-loop (By similarity). In contrast, interaction with the replication protein A (RPA/RP-A) complex inhibits DNA unwinding by HELQ but strongly stimulates DNA strand annealing (By similarity). Triggers displacement of RPA from single-stranded DNA to facilitate annealing of complementary sequences (By similarity). http://togogenome.org/gene/10090:Ormdl2 ^@ http://purl.uniprot.org/uniprot/Q9CQZ0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORM family.|||Ceramide-sensitive subunit of the serine palmitoyltransferase (SPT) complex, which is also composed of SPTLC1, SPTLC2/3 and SPTSSA/B.|||Ceramides bind to ORMDL3 N-terminus and stabilize it in a conformation that physically restricts the accessibility of the substrates to their binding sites in the serine palmitoyltransferase (SPT) complex, hence inhibiting SPT catalytic activity. In the absence of ceramides, the N-terminus is flexible and permits substrate binding, thus liberating SPT from inhibition.|||Endoplasmic reticulum membrane|||No overt phenotype (PubMed:31880535). Simultaneous knockdown of ORMDL1 and ORMDL2 do not exhibit any visible phenotype (PubMed:31880535). Simultaneous knockdown of ORMDL2 and ORMDL3 show elevated brain levels of sphingolipids, compared with wild-type animals, but remain fertile and show no sign of neurodegeneration (PubMed:31880535). The triple knockout ORMDL1, ORMDL2 and ORMDL3 is not viable (PubMed:31880535).|||Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:31880535). When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (By similarity). http://togogenome.org/gene/10090:Spock3 ^@ http://purl.uniprot.org/uniprot/Q571A9|||http://purl.uniprot.org/uniprot/Q8BKV0 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Contains chondroitin sulfate and heparan sulfate O-linked oligosaccharides.|||Expressed in brain.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May participate in diverse steps of neurogenesis. Inhibits the processing of pro-matrix metalloproteinase 2 (MMP-2) by MT1-MMP and MT3-MMP. May interfere with tumor invasion (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Cnih4 ^@ http://purl.uniprot.org/uniprot/Q9CX13 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cornichon family.|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Interacts with Sec23/24 complex components SEC24B and SEC24D (By similarity). Interacts with CCR5 (By similarity). Interacts with ADRB2 in the early secretory pathway (By similarity).|||Involved in G protein-coupled receptors (GPCRs) trafficking from the endoplasmic reticulum to the cell surface; it promotes the exit of GPCRs from the early secretory pathway, likely through interaction with the COPII machinery.|||Membrane http://togogenome.org/gene/10090:Gstp2 ^@ http://purl.uniprot.org/uniprot/P46425 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Pi family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Cannot metabolize 1-chloro-2,4-dinitrobenzene.|||Homodimer.|||Selectively expressed in gall bladder, colon, heart, and skeletal muscle. http://togogenome.org/gene/10090:Ankzf1 ^@ http://purl.uniprot.org/uniprot/J3QM81|||http://purl.uniprot.org/uniprot/Q80UU1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ANKZF1/VMS1 family.|||Cytoplasm|||Endonuclease that cleaves polypeptidyl-tRNAs downstream of the ribosome-associated quality control (RQC) pathway to release incompletely synthesized polypeptides for degradation. The RQC pathway disassembles aberrantly stalled translation complexes to recycle or degrade the constituent parts. ANKZF1 acts downstream disassembly of stalled ribosomes and specifically cleaves off the terminal 3'-CCA nucleotides universal to all tRNAs from polypeptidyl-tRNAs, releasing (1) ubiquitinated polypeptides from 60S ribosomal subunit for degradation and (2) cleaved tRNAs. ANKZF1-cleaved tRNAs are then repaired and recycled by ELAC1 and TRNT1. Also plays a role in the cellular response to hydrogen peroxide and in the maintenance of mitochondrial integrity under conditions of cellular stress.|||Interacts (via VIM motif) with VCP.|||The VLRF1 domain mediates binding to the 60S ribosomal subunit. http://togogenome.org/gene/10090:Cpb2 ^@ http://purl.uniprot.org/uniprot/Q9JHH6 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.|||Plasma; synthesized in the liver.|||Secreted|||TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-323 (By similarity). http://togogenome.org/gene/10090:Hsdl1 ^@ http://purl.uniprot.org/uniprot/Q8BTX9 ^@ Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although it belongs to the SDR family, Phe-218 is present instead of the conserved Tyr which is an active site residue. It is therefore expected that this protein lacks oxidoreductase activity.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.|||Interacts with STYXL1.|||Mitochondrion http://togogenome.org/gene/10090:Ifi205 ^@ http://purl.uniprot.org/uniprot/Q8CGE8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HIN-200 family.|||May act as a transcriptional regulator in the myeloid lineage. Inhibits cell growth via p53/TP53 and RB1-dependent and independent pathways (By similarity).|||Nucleus http://togogenome.org/gene/10090:S100a16 ^@ http://purl.uniprot.org/uniprot/Q9D708 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the S-100 family.|||Calcium-binding protein. Binds one calcium ion per monomer (PubMed:17030513). Can promote differentiation of adipocytes (in vitro). Overexpression in 3T3-L1 preadipocytes increases their proliferation, enhances adipogenesis and reduces insulin-stimulated glucose uptake (PubMed:21266506, PubMed:23526364).|||Cytoplasm|||Homodimer (PubMed:17030513). Interacts with TP53 (PubMed:21266506).|||S100A16 proteins, but not other S100 proteins, have only one functional Ca(2+) binding site per monomer (PubMed:14684152, PubMed:17030513). Upon Ca(2+) binding, undergoes conformational changes leading to the exposure of hydrophobic patches which could be implicated in the Ca(2+)-dependent nuclear export. Binds Zn(2+) (PubMed:17030513). Ca(2+) and Zn(2+) do not bind to the same site (PubMed:17030513). Does not bind Cu(2+) (PubMed:17030513).|||Ubiquitous (PubMed:17030513). Widely distributed throughout the adult brain and predominantly expressed within specific astrocyte populations (PubMed:17030513). Expressed at high level in adipose tissues of obese animals (PubMed:21266506).|||nucleolus http://togogenome.org/gene/10090:Sema3e ^@ http://purl.uniprot.org/uniprot/P70275 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Detected in neurons in the thalamus. Detected in embryonic vasculature. Developing lungs, developing skeletal elements and ventral horns of the developing neural tube. Correlates positively with tumor progression.|||Embryos present defects in the patterning of intersomitic vasculature.|||Interacts with PLXND1.|||Plays an important role in signaling via the cell surface receptor PLXND1. Mediates reorganization of the actin cytoskeleton, leading to the retraction of cell projections. Promotes focal adhesion disassembly and inhibits adhesion of endothelial cells to the extracellular matrix. Regulates angiogenesis, both during embryogenesis and after birth. Can down-regulate sprouting angiogenesis. Required for normal vascular patterning during embryogenesis. Plays an important role in ensuring the specificity of synapse formation.|||Secreted http://togogenome.org/gene/10090:Ppwd1 ^@ http://purl.uniprot.org/uniprot/Q8CEC6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclophilin-type PPIase family. PPIL1 subfamily.|||Identified in the spliceosome C complex.|||Inhibited by cyclosporin A (CsA).|||Nucleus|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. May be involved in pre-mRNA splicing. http://togogenome.org/gene/10090:Necab2 ^@ http://purl.uniprot.org/uniprot/Q91ZP9 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in retina, retinal pigmented epithelium, Rathke's pouch, corneal epithelium, the infundibulum and olfactory placodes at 10.5 dpc (at protein level). Expressed in the inner region of the neural retina, including the ganglion cell layer at 17.5 dpc (at protein level). Expressed in the optic sulcus and in the pre-tectum at 8.5 dpc. Expressed in the optic vesicle, in the midline position in the roof of the midbrain and in the pre-tectum at 9.0-9.5 dpc. Expressed in the olfactory placodes at 10.5 dpc. Expressed in retinal-pigmented epithelium and in the neural retina, with strong expression in the ciliary margin at 12.5-13.5 dpc.|||Expressed in the iris, in the ciliary margin of the retina and in the inner portion of the neural retina. Expressed in the spinal dorsal horn with especially strong expression in lamina IIi; found in excitory synaptic boutons (at protein level).|||Interacts (calcium-dependent) with ADORA2A and GRM5.|||May act as a signaling scaffold protein that senses intracellular calcium. Can modulate ligand-induced internalization of ADORA2A and coupling efficiency of mGluR5/GRM5; for both receptors may regulate signaling activity such as promoting MAPK1/3 (ERK1/2) activation.|||Up-regulated by PAX6.|||axon|||dendrite http://togogenome.org/gene/10090:Mrtfa ^@ http://purl.uniprot.org/uniprot/Q8K4J6 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected throughout the embryo at 10.5 dpc; higher expression is found at 13.5 dpc in neural mesenchymal cells, skeletal muscle of the tongue, and epithelial cells of the colon and small intestine; at 15.5 dpc, expression in epithelial cells of lung, kidney, bladder, and colon is also detected.|||Expressed in heart, brain, spleen, lung, liver, muscle, kidney and testis.|||Interacts with SRF, forming the SRF-MRTFA nuclear complex which binds the 5'-CArG-3' consensus motif (CArG box) on DNA via SRF (PubMed:12732141, PubMed:19350017). Interacts (via RPEL repeats) with globular actin (G-actin), thereby regulating its subcellular location and activity of the complex formed with SRF (PubMed:12732141, PubMed:17588931, PubMed:19350017, PubMed:19008859, PubMed:27304076, PubMed:21673315). Either forms a trivalent (by binding three G-actin monomers) or pentavalent (by binding five G-actin monomers) complex with G-actin (PubMed:21673315). Forms a nuclear ternary complex with SCAI and SRF, leading to suppress MRTFA-induced SRF transcriptional activity (PubMed:19350017). Interacts with beta-actin (ACTB); interaction with ACTB prevents interaction with SCAI (PubMed:19350017). Interacts with MRTFB (By similarity).|||Nucleus|||Phosphorylation at Ser-41 by Erk inhibits binding of globular actin (G-actin), unmasking the nuclear localization signal (NLS) and promoting nuclear import.|||Some publications use a protein sequence that is longer at the N-terminus and is based on an artificial construct (PubMed:12732141, PubMed:27304076). The sequence used in these publications modifies a non-canonical CTG leucine codon upstream of the initiator codon into ATG, generating a protein of 1021 residues (PubMed:12732141, PubMed:27304076). The existence of this form has not been confirmed in vivo and is therefore unsure (PubMed:12732141, PubMed:27304076). Similarly, the existence of the S33 ('Ser-33') phosphorylation site described in Panayiotou et al. is unsure (PubMed:27304076).|||The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity.|||The RPEL repeats mediate binding to globular actin (G-actin); each RPEL repeat-binding to one G-actin monomer (PubMed:19008859, PubMed:21673315). In addition, each intervening spacer sequence region can bind one G-actin monomer, to reach a pentavalent complex (PubMed:21673315).|||Transcription coactivator that associates with the serum response factor (SRF) transcription factor to control expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration (PubMed:12019265, PubMed:12732141, PubMed:17588931, PubMed:19350017, PubMed:24732378). The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics (PubMed:24732378). MRTFA binds G-actin via its RPEL repeats, regulating activity of the MRTFA-SRF complex (PubMed:12732141, PubMed:17588931). Activity is also regulated by filamentous actin (F-actin) in the nucleus (PubMed:23558171, PubMed:25759381). http://togogenome.org/gene/10090:Cmtm8 ^@ http://purl.uniprot.org/uniprot/Q9CZR4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chemokine-like factor family.|||Membrane http://togogenome.org/gene/10090:Ier5 ^@ http://purl.uniprot.org/uniprot/O89113|||http://purl.uniprot.org/uniprot/Q3UJ54 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IER family.|||By serum and growth factors.|||Cytoplasm|||Monomer. Homodimer. Associates with the catalytic subunit of protein phosphatase PP2A. Interacts (via N- and C-terminal regions) with PPP2R2B. Interacts with PPP2R2A, PPP2R2C and PPP2R2D. Interacts (via N-terminus) with RPS6KB1. Interacts (via central region) with HSF1; this interaction promotes PPP2CA-induced HSF1 dephosphorylation, leading to enhanced HSF1 transcriptional activity.|||Nucleus|||Plays a role as a transcription factor. Mediates positive transcriptional regulation of several chaperone gene during the heat shock response in a HSF1-dependent manner. Mediates negative transcriptional regulation of CDC25B expression. Plays a role in the dephosphorylation of the heat shock factor HSF1 and ribosomal protein S6 kinase (S6K) by the protein phosphatase PP2A. Involved in the regulation of cell proliferation and resistance to thermal stress. Involved in the cell cycle checkpoint and survival in response to ionizing radiation. Associates with chromatin to the CDC25B promoter. http://togogenome.org/gene/10090:Ngp ^@ http://purl.uniprot.org/uniprot/O08692 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an inhibitor of cathepsin B (CTSB) activity. Plays a role as a negative regulator of tumor vascular development, cell invasion and metastasis.|||Belongs to the cathelicidin family.|||Cytoplasmic granule|||Expressed in myeloid bone marrow cells. Expressed in neutrophilic precursors (at protein level) (PubMed:8749713). Expressed in myeloid bone marrow cells (PubMed:21518852).|||Monomer. Homodimer; disulfide-linked.|||Secreted|||Up-regulated by CCAAT/enhancer-binding proteins CEBPA and CEBPE and transcription factor SPI1 (at protein level) (PubMed:12515729). Down-regulated in malignant tumor conditioned medium (PubMed:21518852). Up-regulated during early bone marrow differentiation by the granulocyte-macrophage colony-stimulating factor CSF2 and down-regulated during granulocytic maturation (PubMed:8749713). http://togogenome.org/gene/10090:Mzf1 ^@ http://purl.uniprot.org/uniprot/A1L358|||http://purl.uniprot.org/uniprot/S4R1L6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Snx1 ^@ http://purl.uniprot.org/uniprot/Q6NZD2|||http://purl.uniprot.org/uniprot/Q9WV80 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Binds phosphatidylinositol 3-phosphate (PtdIns-(3)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2) in liposome-based assays. Can bind PtdIns(3,4,5)P3 in protein:lipid overlay assays, but not in liposome-based assays (By similarity).|||Early endosome membrane|||Endosome membrane|||Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity. Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1). Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi. Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R. Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN. Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking (By similarity).|||Membrane|||No visible phenotype. Mice are born at the expected Mendelian ratio and are fertile. Mice lacking both Snx1 and Snx2 die during embryonic development, around 9.5 and 11.5 dpc.|||Predominantly forms heterodimers with BAR domain-containing sorting nexins SNX5, SNX6 and SNX32 (By similarity). Can self-associate to form homodimers (PubMed:11726276). The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS) and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. Interacts with SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35, DRD5, DENND5A, KALRN, RHOG (GDP-bound form). The interaction with SNX2 is reported controversially. Interacts with DNAJC13; prevented by presence of HGS. Interacts with HGS (By similarity).|||The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of a N-terminal amphipathic helix (AH) in the membrane (By similarity).|||lamellipodium|||trans-Golgi network membrane http://togogenome.org/gene/10090:Tor2a ^@ http://purl.uniprot.org/uniprot/Q8R1J9 ^@ Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16 dpc, widely expressed in all tissues tested.|||Belongs to the ClpA/ClpB family. Torsin subfamily.|||Endoplasmic reticulum lumen|||Expressed at similar levels in liver, muscle and brain (at protein level).|||Homohexamer. Interacts with TOR1AIP1.|||N-glycosylated. http://togogenome.org/gene/10090:Camk1g ^@ http://purl.uniprot.org/uniprot/Q91VB2 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin is thought to result in a conformational change and leads to activation through phosphorylation by CAMKK1.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates transcription factor CREB1.|||Cell membrane|||Cytoplasm|||Expression starts at 11 dpc in parallel with the onset of development of the central nervous system.|||Golgi apparatus membrane|||Highly expressed in brain, in neuronal cell bodies of the central nucleus of amygdala and ventromedial hypothalamic nucleus. Also detected in heart, testis, and kidney.|||May be prenylated on Cys-474.|||The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate. http://togogenome.org/gene/10090:Pdk4 ^@ http://purl.uniprot.org/uniprot/O70571|||http://purl.uniprot.org/uniprot/Q544J2 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PDK/BCKDK protein kinase family.|||Homodimer. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (By similarity).|||Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.|||Mitochondrion matrix|||No visible phenotype at birth. Mice have lower blood glucose and pyruvate levels after overnight fasting than normal, while the levels of ketone bodies are increased. After 48 hours of starving, their rate of glucose oxidation is increased, and glycolysis decreased, compared to wild type mice. Likewise, their rate of fatty acid oxidation is lower than normal in response to starvation. In contrast, there are no differences in blood glucose levels between fed mutant and wild type mice. In response to a high-fat diet, mutant mice have lower de novo fatty acid biosynthesis, and lower liver steatosis than wild-type. Mutant mice show normal bone formation and normal bone metabolism, excepting reduced bone loss when suspended to induce disuse osteoporosis.|||Up-regulated by PPARD. http://togogenome.org/gene/10090:Ankdd1b ^@ http://purl.uniprot.org/uniprot/Q14DN9 ^@ Miscellaneous ^@ Sequence identified by Havana. http://togogenome.org/gene/10090:Or8k25 ^@ http://purl.uniprot.org/uniprot/Q7TR72 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Or51a42 ^@ http://purl.uniprot.org/uniprot/Q8VGY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hormad1 ^@ http://purl.uniprot.org/uniprot/Q9D5T7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Cytoplasm|||Expressed in spermatocytes from P10 to adulthood. Expressed in oocytes from 12.5 dpc to P9. Primarily detected in spermatocytes and less in spermatids or spermatogonia. Abundant in the nuclei of pachytene and zygotene cells. Also detected in nuclei of diplotene cells (at protein level).|||Interacts with HORMAD2 (PubMed:22549958). Interacts with IHO1 (PubMed:27723721).|||Mice develop normally without obvious somatic defects but males and females are sterile. Although spermatocytes are present in testis tubules at epithelial cycle stage III-IV, they undergo apoptosis by the end of stage IV, and post-meiotic cells are not found in testes, suggesting that spermatocytes are eliminated at a stage equivalent to mid-pachytene. In females, ovarian development is grossly normal, eggs fertilize and embryonic development arrests at blastocyst stage due to aneuploidy.|||Nucleus|||Phosphorylated at Ser-375 in a SPO11-dependent manner.|||Plays a key role in meiotic progression (PubMed:19686734, PubMed:21079677, PubMed:21478856). Regulates 3 different functions during meiosis: ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends (PubMed:19686734, PubMed:21079677). Promotes synaptonemal-complex formation independently of its role in homology search (PubMed:19686734, PubMed:21079677). Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes (PubMed:21478856).|||Specifically expressed in meiotic germ cells. http://togogenome.org/gene/10090:Calhm5 ^@ http://purl.uniprot.org/uniprot/Q8R100 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CALHM family.|||Membrane|||Pore-forming subunit of a voltage-gated ion channel. http://togogenome.org/gene/10090:Akap7 ^@ http://purl.uniprot.org/uniprot/O55074|||http://purl.uniprot.org/uniprot/Q7TN79 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds cAMP-dependent protein kinase (PKA). Interacts with PRKCA; only the cytoplasmic form is capable of interacting with PRKCA (By similarity).|||Cytoplasm|||Expressed in oocytes.|||Lateral cell membrane|||Nucleus|||Probably targets cAMP-dependent protein kinase (PKA) to the cellular membrane or cytoskeletal structures. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium (By similarity).|||Targets the cAMP-dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L-type calcium channel. The membrane-associated form reduces epithelial sodium channel (ENaC) activity, whereas the free cytoplasmic form may negatively regulate ENaC channel feedback inhibition by intracellular sodium (By similarity). http://togogenome.org/gene/10090:Mrps36 ^@ http://purl.uniprot.org/uniprot/Q9CQX8|||http://purl.uniprot.org/uniprot/Q9D6T9 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-ketoglutarate dehydrogenase component 4 family.|||May be necessary to recruit DLD/E3 to the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDC) core composed of OGDH/E1-DLST/E2, hence stabilizes the complex.|||Mitochondrion|||Probable component of the 2-oxoglutarate dehydrogenase complex (OGDC), composed of OGDH (2-oxoglutarate dehydrogenase; also called E1 subunit), DLST (dihydrolipoamide succinyltransferase; also called E2 subunit) and DLD (dihydrolipoamide dehydrogenase; also called E3 subunit) (Probable). Within OGDC, may interact (via N-terminus) with E3 subunit and (via C-terminus) with the complex core formed by E1 and E2 subunits (Probable).|||Was originally identified in the small subunit (28S) of mitochondrial ribosomes that were purified on sucrose gradients (By similarity). This observation has been challenged by experiments showing MRPS36 copurification with the oxoglutarate dehydrogenase complex (OGDC), also called alpha-ketoglutarate dehydrogenase complex (KGDH). Both mitochondrial ribosome 28S subunit and OGDC have a similar size and OGDC is highly abundant, therefore OGDC has been found to contaminate ribosomal preparations performed by sequential centrifugation steps (PubMed:25165143). In addition, MRPS36 could not be located in the structure of the human mitochondrial ribosome, supporting the hypothesis that it is not a mitoribosomal protein (By similarity). http://togogenome.org/gene/10090:Pax6 ^@ http://purl.uniprot.org/uniprot/P63015|||http://purl.uniprot.org/uniprot/Q8VBX9 ^@ Developmental Stage|||Disease Annotation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the newborn eye.|||Belongs to the paired homeobox family.|||Cytoplasm|||Defects in Pax6 are the cause of a condition known as small eye (Sey) which results in the complete lack of eyes and nasal primordia.|||Dominant isoform expressed in the eye, including in the retina and cornea (PubMed:21084637). Abundantly expressed in the lens epithelium (PubMed:21084637).|||Dominant isoform expressed in the eye, including in the retina and cornea (PubMed:21084637). Weakly expressed in the lens epithelium (PubMed:21084637).|||Expressed in osteoclasts.|||Expressed in the developing eye at 9.5 dpc, the expression becomes much stronger and additionally expressed in the neural tube and optic and lens vesicles at 11.5 dpc. Expression is then reduced by 12.5 dpc and becomes significantly decreased from 14.5 dpc to 18.5 dpc of embryonic development.|||Expressed in the developing eye, nose, brain and pancreas (PubMed:21084637). At 9 dpc, expressed in the telencephalon, diencephalon, neural tube, optic vesicle and pancreas. Throughout development, expression continues in the dorsal and ventral pancreas. Expressed during cortical neurogenesis from 11 to 18 dpc. High levels in the early radial glial progenitors from 11 to 14 dpc and gradually decrease thereafter (at protein level). During corticogenesis, the protein level declines faster than that of the mRNA, due to proteasomal degradation (PubMed:18628401).|||Induced by TNFSF11/RANKL-induced osteoclastogenesis.|||Interacts with MAF and MAFB (PubMed:17901057). Interacts with TRIM11; this interaction leads to ubiquitination and proteasomal degradation, as well as inhibition of transactivation, possibly in part by preventing PAX6 binding to consensus DNA sequences (PubMed:18628401). Interacts with TLE6/GRG6 (PubMed:23990468).|||Nucleus|||Significantly expressed in the newborn eye.|||Sumoylated by SUMO1 at 'Lys-91'.|||Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (PubMed:9163426). Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains (By similarity). Acts as a transcriptional repressor of NFATC1-mediated gene expression (PubMed:23990468).|||Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal degradation. http://togogenome.org/gene/10090:Ccdc124 ^@ http://purl.uniprot.org/uniprot/Q9D8X2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with translationally inactive ribosomes in the nonrotated state. Interacts with RASGEF1B.|||Belongs to the CCDC124 family.|||Midbody|||Ribosome-binding protein involved in ribosome hibernation: associates with translationally inactive ribosomes and stabilizes the nonrotated conformation of the 80S ribosome, thereby promoting ribosome preservation and storage. Also required for proper progression of late cytokinetic stages.|||centrosome http://togogenome.org/gene/10090:Mid1ip1 ^@ http://purl.uniprot.org/uniprot/Q4FK31|||http://purl.uniprot.org/uniprot/Q9CQ20 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPOT14 family.|||Cytoplasm|||Down-regulated by fasting. Up-regulated by a carbohydrate-rich diet.|||During embryonic development, expressed mainly in the neuroepithelial midline, urogenital apparatus and digits. Detected in adult white fat, liver, heart, brain and kidney. Expressed at very low levels in lactating mammary gland.|||Homodimer in the absence of THRSP. Heterodimer with THRSP. The homodimer interacts with ACACA and ACACB. Promotes polymerization of Acetyl-CoA carboxylase to form complexes that contain MID1IP1 and ACACA and/or ACACB. Interaction with THRSP interferes with ACACA binding.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Nucleus|||Plays a role in the regulation of lipogenesis in liver. Up-regulates ACACA enzyme activity. Required for efficient lipid biosynthesis, including triacylglycerol, diacylglycerol and phospholipid. Involved in stabilization of microtubules.|||cytoskeleton http://togogenome.org/gene/10090:Pou3f2 ^@ http://purl.uniprot.org/uniprot/P31360 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family. Class-3 subfamily.|||Expressed specifically in the neuroectodermal cell lineage.|||Interacts with PQBP1 (By similarity). Interaction with ISL1 (PubMed:24643061).|||Nucleus|||Transcription factor that plays a key role in neuronal differentiation (PubMed:24243019). Binds preferentially to the recognition sequence which consists of two distinct half-sites, ('GCAT') and ('TAAT'), separated by a non-conserved spacer region of 0, 2, or 3 nucleotides (By similarity). Acts as a transcriptional activator when binding cooperatively with SOX4, SOX11, or SOX12 to gene promoters (PubMed:18505825, PubMed:18403418). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (PubMed:20107439, PubMed:24243019, PubMed:27281220). Acts downstream of ASCL1, accessing chromatin that has been opened by ASCL1, and promotes transcription of neuronal genes (PubMed:24243019). http://togogenome.org/gene/10090:Cdk7 ^@ http://purl.uniprot.org/uniprot/Q03147|||http://purl.uniprot.org/uniprot/Q3THG5 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor; this complex is sensitive to UV light. The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI (By similarity). Interacts with HINT1 (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Nucleus|||Phosphorylation at Thr-170 is required for enzymatic activity. The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminal domain (CTD), thus stopping cell cycle progression (By similarity).|||Phosphorylation of Ser-164 during mitosis inactivates the enzyme. Phosphorylation of Thr-170 is required for activity. Phosphorylated at Ser-164 and Thr-170 by CDK2 (By similarity).|||Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.|||perinuclear region http://togogenome.org/gene/10090:Slc25a1 ^@ http://purl.uniprot.org/uniprot/Q8JZU2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Expressed minimally but ubiquitously throughout the adult brain. Detected at higher levels in the olfactory bulb, neocortex and cerebellum. Also expressed in a subset of large cells in the globus pallidus.|||Expression reaches a maximum between 16 dpc and P0 and then declines in adulthood.|||Mitochondrial electroneutral antiporter that exports citrate from the mitochondria into the cytosol in exchange for malate. Also able to mediate the exchange of citrate for isocitrate, phosphoenolpyruvate, cis-aconitate and to a lesser extend cis-aconitate, maleate and succinate. In the cytoplasm citrate is important in the regulation of glycolysis through a feedback mechanism and in the production of acetyl-CoA which is needed for the synthesis of fatty acids, sterols, prostaglandins, dolichol and coenzyme Q (CoQ). Required for proper neuromuscular junction formation.|||Mitochondrion inner membrane|||Mitochondrion membrane|||Possesses a short cleavable presequence, which, however, is found to be dispensable both for targeting to mitochondria and insertion into the inner membrane. However, the presequence is required to keep SLC25A1 in a soluble state and thus in an import-competent state. Mature SLC25A1 lacking the presequence is prone to aggregation. http://togogenome.org/gene/10090:Arhgef4 ^@ http://purl.uniprot.org/uniprot/Q7TNR9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion (By similarity). Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.|||Cytoplasm|||Expressed in colon epithelial cells. Highly expressed in CNS, including hippocampus, olfactory bulb and cerebellum. Expression is aberrantly enhanced in most colorectal tumors.|||In an autoinhibited form the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site.|||Interacts with RHOA and RAC1, and APC. Found in a complex consisting of ARHGEF4, APC and CTNNB1 (By similarity). http://togogenome.org/gene/10090:Dach1 ^@ http://purl.uniprot.org/uniprot/Q9QYB2 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DACH/dachshund family.|||Expressed at higher levels in adult kidney and lung, and at lower levels in brain and testis. Expressed in embryonal kidneys, eyes, cochleae and limb buds.|||Highest expression was found at 11.5 dpc, and expression rapidly declines at later stages of the development. Between 8.0 and 13.5 dpc is found in neural crest cells during their pre-migratory, migratory, and, in some cases post-migratory phase throughout the body axis. Also found in lateral mesenchyme of trunk and head. At 10 and 12 dpc found in mesonephric tubules. At 16 dpc found in epithalial cells of metanephric 'comma' and 'S'-shaped bodies, in mesenchymal cells of the medulla and the cortex. Colocalized to the nucleus of glomerular podocytes and epithelial cells lining many of the convoluted tubes. At 10.5 dpc found in both the anterior and posterior of the limb bud. At 11.5 dpc expression becomes increasingly peripheral, extending around the entire handplate in the mesenchymal cells underlying the apical ectodermal ridge. At 12.5 dpc expression is entirely peripheral an by 13.5 dpc is localized to the mesenchyme at the distal tips of the digits. At 10 dpc found in cells of the optic cup and in some cells surrounding the eye. At 12 dpc found in developing lens fibers, the ectoderm overlaying the developing eye and less intensely in the retina. At 12 dpc found in cells of the dorsomedial and dorsolateral epithelium of the otic vesicle. At later stages expressed in only a few specialized cell types of the cochlear duct, including the inner and outer hair cells, stria vascularis, and the mesenchymal cells directly underlying the organ of Corti. From 10.5 to 12.5 dpc expressed in the telencephalon including the olfactory bulbs, throughout the length of the neural tube and within the dorsal root ganglia, in cranial ganglia in the trigeminal ganglion and the glossopharyngeal-vagal ganglion complex. At 10.5 and 11.5 dpc expressed in punctate pattern on the ventral side of the embryo between the fore and hind limbs, the rib primordia; this expression disappears by 12.5 dpc. At 11.5 and 12.5 dpc found in genital eminence.|||Interacts with SIX1, SIX6 and EYA3. Interacts with NCOR1 and HDAC3 through its N-terminus. Interacts with SIN3A through its C-terminus. Interacts with SMAD3 and SMAD4 (By similarity).|||Nucleus|||The DACHbox-N/DD1 domain forms a structure containing a DNA binding motif similar to that of the forkhead/winged helix domain.|||Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator of SIX1, SIX6 and probably SIX5. Corepression of precursor cell proliferation in myoblasts by SIX1 is switched to coactivation through recruitment of EYA3 to the SIX1-DACH1 complex. Transcriptional activation seems also to involve association of CREBBP. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. Inhibits TGF-beta signaling through interaction with SMAD4 and NCOR1 (By similarity). Binds to chromatin DNA via its DACHbox-N domain. http://togogenome.org/gene/10090:Cfap45 ^@ http://purl.uniprot.org/uniprot/Q9D9U9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CFAP45 family.|||Expressed in respiratory cells and in sperm (at protein level).|||Interacts with AK8; dimerization with AK8 may create a cavity at the interface of the dimer that can accommodate AMP (By similarity). Interacts with CFAP52 (By similarity). Interacts with ENKUR (By similarity). Directly interacts with DNALI1 (By similarity). Interacts with DNAH11 (By similarity). Interacts with DNAI1 (By similarity).|||Knockout animals display left-right asymmetry abnormalities, including situs inversus totalis. Nodal cilia rotational speed is reduced compared to heterozyous littermates. Mutant males also exhibit asthenospermia and are infertile.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). It is an AMP-binding protein that may facilitate dynein ATPase-dependent ciliary and flagellar beating via adenine nucleotide homeostasis. May function as a donor of AMP to AK8 and hence promote ADP production (PubMed:33139725).|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Scel ^@ http://purl.uniprot.org/uniprot/Q9EQG3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in the upper layers of stratified epithelia, including, ependyma and choroid plexus of the brain ventricles.|||May function in the assembly or regulation of proteins in the cornified envelope. The LIM domain may be involved in homotypic or heterotypic associations and may function to localize sciellin to the cornified envelope (By similarity).|||Membrane|||Strong expression was seen in 17-17.5 day-old embryos. Expression was also detected in the amnion of 17.5 day-old embryo. http://togogenome.org/gene/10090:Slbp ^@ http://purl.uniprot.org/uniprot/P97440|||http://purl.uniprot.org/uniprot/Q3TSD8|||http://purl.uniprot.org/uniprot/Q3U4T7|||http://purl.uniprot.org/uniprot/Q8K2W7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Amino acids 31-34, 96-99 and 246-249 are necessary for interaction with the Importin alpha/Importin beta receptor. The first 18 amino acids, amino acids 69-76 and 179-182 are necessary for interaction with TNPO3. Amino acids 31-34, 96-99 and 246-249 are necessary for nuclear localization (By similarity).|||Belongs to the SLBP family.|||Cytoplasm|||Females show no impaired oogenesis but display a defect in the formation of primordial follicles leading to infertility. Most embryos arrested at the 2-cell stage and fail to complete the second round of DNA replication due to an insufficient supply of histone H3 and H4. Accumulation of histone H2A and H2B is not affected.|||Monomer. SLBP/pre-mRNA complex interacts with ZNF473 (By similarity). Interacts with the Importin alpha/Importin beta receptor, LSM1, MIF4GD, TNPO3 and UPF1 (By similarity). Interaction with LSM1 occurs when histone mRNA is being rapidly degraded during the S phase (By similarity). Found in a ternary complex with ERI1 and the stem-loop structure of the 3' end of histone mRNA. Associates with polyribosomes (By similarity). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (PubMed:19470752). Binds in a cooperative manner with ERI1 to the mature 3'-end of histone mRNAs (PubMed:19470752).|||Nucleus|||Phosphorylated on Thr-61 and Thr-62 in the S-phase. Phosphorylation of Thr-62 by CDK1 primes phosphorylation of Thr-61 by CK2. Phosphorylation of Thr-62 is required for its degradation at the end of the S phase. Its degradation is not required for histone mRNA degradation at the end of the S phase. All the phosphorylated forms detected are present in the cytoplasm. Both unphosphorylated and phosphorylated forms bind the stem-loop structure of histone mRNAs. Phosphorylation at Thr-171 increases affinity for histone mRNAs (By similarity).|||RNA-binding protein involved in the histone pre-mRNA processing (PubMed:18036581). Binds the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilizing the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) (PubMed:18036581). Plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery (By similarity). Stabilizes mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression (By similarity). Involved in the mechanism by which growing oocytes accumulate histone proteins that support early embryogenesis (PubMed:18036581). Binds to the 5' side of the stem-loop structure of histone pre-mRNAs (PubMed:19470752).|||Ubiquitinated by the CRL2(FEM1A), CRL2(FEM1B) and CRL2(FEM1C) complexes, leading to its degradation.|||Widely expressed. Expressed in growing primary but not non-growing oocytes, within the primordial follicles. Also detected in fully-grown oocytes in antral follicles (at protein level). http://togogenome.org/gene/10090:Lrrc7 ^@ http://purl.uniprot.org/uniprot/A0A0G2JDT9|||http://purl.uniprot.org/uniprot/A0A571BEA5|||http://purl.uniprot.org/uniprot/E9Q6L9|||http://purl.uniprot.org/uniprot/Q80TE7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LAP (LRR and PDZ) protein family.|||Cytoplasm|||Expressed in brain (at protein level).|||Interacts with CNKSR2 and DLG4 (By similarity). Interacts with CTNND2/Catenin delta-2. Forms a complex with N-cadherin through CTNND2. Interacts with CAMK2A (By similarity).|||Mutant mice are viable and were born at the expected Mendelian ratio, but they have a mortality rate of about 20%. They show early growth retardation. Mutant animals exhibit behavioral abnormalities, including clasping when suspended by the tail, impaired both hippocampus-dependent and hippocampus-independent short-term memories and absence of acoustic prepulse inhibition. They also exhibit significantly higher levels of anxiety. They become hyperactive in response to stress or novelty, but are more sedentary than wild-type in a familiar environment. Males have a profound deficit in nest-making behavior and were aggressive when group-housed, even with littermates.|||Postsynaptic density|||Required for normal synaptic spine architecture and function. Necessary for DISC1 and GRM5 localization to postsynaptic density complexes and for both N-methyl D-aspartate receptor-dependent and metabotropic glutamate receptor-dependent long term depression. http://togogenome.org/gene/10090:Commd5 ^@ http://purl.uniprot.org/uniprot/Q8R395 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL2, CUL3, CUL4A, CUL4B, CUL7.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Negatively regulates cell proliferation. Negatively regulates cell cycle G2/M phase transition probably by transactivating p21/CDKN1A through the p53/TP53-independent signaling pathway. Involved in kidney proximal tubule morphogenesis. Down-regulates activation of NF-kappa-B.|||Nucleus http://togogenome.org/gene/10090:Dnajc12 ^@ http://purl.uniprot.org/uniprot/Q9R022 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with HSPA8.|||Ubiquitous. Highest levels of expression in kidney. http://togogenome.org/gene/10090:Entpd2 ^@ http://purl.uniprot.org/uniprot/O55026|||http://purl.uniprot.org/uniprot/Q921R1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GDA1/CD39 NTPase family.|||By dioxin.|||Cell membrane|||In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Hydrolyzes ADP only to a marginal extent (By similarity). http://togogenome.org/gene/10090:Asrgl1 ^@ http://purl.uniprot.org/uniprot/Q8C0M9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Ntn-hydrolase family.|||Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme. The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.|||Cytoplasm|||Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.|||Heterodimer of an alpha and beta chain produced by autocleavage. This heterodimer may then dimerize in turn, giving rise to a heterotetramer.|||High expression in the heart and brain while low to minimal expression in the other tissues. In ocular tissues, high levels is observed in the optic nerve and retina while relatively low levels of expression are detected in the iris-ciliary body, lens or retinal pigment epithelium. http://togogenome.org/gene/10090:Rp9 ^@ http://purl.uniprot.org/uniprot/P97762 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to PIM1. Binds to ZNHIT4.|||Highly expressed in the testis, moderately in the kidney, liver and spleen, and weakly in the skeletal muscle and heart.|||Is thought to be a target protein for the PIM1 kinase. May play some roles in B-cell proliferation in association with PIM1.|||Nucleus http://togogenome.org/gene/10090:Atrx ^@ http://purl.uniprot.org/uniprot/Q61687 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Citrullinated by PADI4.|||Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.|||Interacts with DAXX to form the chromatin remodeling complex ATRX:DAXX. Probably binds EZH2. Binds annexin V in a calcium and phosphatidylcholine/phosphatidylserine-dependent manner. Interacts directly with CBX5 via the PxVxL motif. Interacts with RAD50, MRE11 and NBN; indicative for an association with the MRN complex. Interacts with histone MACROH2A1. Interacts with histone H3 peptides methylated at 'Lys-10' with preferences H3K9me3 > H3K9me2 > H3K9me1. Interacts with histone H3 peptides unmethylated at 'Lys-5' (H3K4me0). Interacts with MECP2, SMC1 and SMC3. Interacts with SETDB1, TRIM28 and ZNF274 (By similarity).|||Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3-containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells probably implying recruitment of CBX5 to telomeres. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according (PubMed:20211137) is required for its transcriptional repression in embryonic stem cells. Acts as negative regulator of chromatin incorporation of transcriptionally repressive histone MACROH2A1, particularily at telomeres. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc-finger genes (By similarity).|||Nucleus|||PML body|||The ADD domain predominantly interacts with histone H3 trimethylated at 'Lys-10'(H3K9me3) (and to a lesser extent H3 mono- or dimethylated at 'Lys-10') and simultanously to histone H3 unmethylated at 'Lys-5' (H3K4me0). The interaction with H3K9me3 is disrupted by the presence of H3K4me3 suggesting a readout of the combined histone H3 methylation state (By similarity).|||telomere http://togogenome.org/gene/10090:Pxdn ^@ http://purl.uniprot.org/uniprot/Q3UQ28 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxidase family. XPO subfamily.|||Binds 1 Ca(2+) ion per subunit.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per subunit.|||Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncross-linked collagen IV/COL4A1 NC1 hexamer (PubMed:31817535, PubMed:22842973, PubMed:29626421, PubMed:25708780, PubMed:28424209). In turns, directly contributes to the collagen IV network-dependent fibronectin/FN and laminin assembly, which is required for full extracellular matrix (ECM)-mediated signaling (By similarity). Thus, sulfilimine cross-links are essential for growth factor-induced cell proliferation and survival in endothelial cells, an event essential to basement membrane integrity (By similarity). In addition, through the bromide oxidation, may promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and FAK pathways (By similarity). Moreover brominates alpha2 collagen IV chain/COL4A2 at 'Tyr-1480' and leads to bromine enrichment of the basement membranes (PubMed:32675287, PubMed:32571911). In vitro, can also catalyze the two-electron oxidation of thiocyanate and iodide and these two substrates could effectively compete with bromide and thus inhibit the formation of sulfilimine bonds (By similarity). Binds laminins (By similarity). May play a role in the organization of eyeball structure and lens development during eye development (PubMed:31817535, PubMed:24895407).|||Cell surface|||Endoplasmic reticulum|||Expressed in all embryonic tissues at 10 dpc. Detected at 7 dpc (PubMed:18848646, PubMed:18929642). At 11.5 dpc, faintly expressed in the lens epithelium cells and in the anterior part of primary fiber cells. At 13.5 dpc, strongly expressed in the developing lens especially the lens epithelium cells and in the inner limiting membrane. Additionally, it is also expressed in ocular mesenchymal cells in the vitreous. At 17.5 dpc, expressed not only in the whole lens, but also in the inner neuroblast layer. In the lens, appears to be strongly expressed in the lens epithelial and at the posterior pole of the lens (PubMed:18929642).|||Highly expressed in the cardiovascular system. In the embryo, expressed in the corneal epithelial layer. In the adult eyes, expressed in the corneal and lens epithelium. Expressed in lung (PubMed:31817535).|||Homotrimer; disulfide-linked. The homotrimer form is predominant. Homooligomer; disulfide-linked. Oligomerization occurs intracellularly before C-terminal proteolytic cleavage (By similarity). Interacts with PXDNL; this interaction inhibits the peroxidase activity of PXDN (By similarity).|||Homozygous mice for the PXDN gene show completely or almost closed eyelids with small eyes, having no apparent external morphological defects in other organs (PubMed:31817535). In addition, mice show hair color change and the tail color is white and also have a white spot at the ventral and dorsal region at a frequency of about 94.1%. Some of mutants have severe cataracts in the eyes (PubMed:31817535).|||Processed by FURIN and the proteolytic processing largely depends on the peroxidase activity of PXDN (PubMed:34679700). The proteolytic cleavage occurs after intracellular homotrimerization and releases into the extracellular matrix a large, catalytically active fragment and a smaller fragment consisting primarily of the C-terminal VWFC domain. The processing enhances both peroxidase activity and sulfilimine cross-links formation (By similarity).|||The VWFC domain mediates the covalent links between monomers throught disulfide bridges. Ig-like C2-type domains are required to sulfilimine bond formation. The VWFC domain is not required for trimerization. The LRR domain mediates high affinity binding to laminin-1.|||Thiocyanate inhibits the formation of 3-bromotyrosine.|||basement membrane|||extracellular matrix http://togogenome.org/gene/10090:Asic4 ^@ http://purl.uniprot.org/uniprot/Q7TNS7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC4 subfamily.|||Homotrimer or heterotrimer with other ASIC proteins.|||In vitro, has no proton-gated channel activity.|||Membrane|||Probable cation channel with high affinity for sodium. http://togogenome.org/gene/10090:Emp3 ^@ http://purl.uniprot.org/uniprot/O35912 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family.|||Membrane|||Probably involved in cell proliferation and cell-cell interactions. http://togogenome.org/gene/10090:Or4b1 ^@ http://purl.uniprot.org/uniprot/Q8VGP3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Epha2 ^@ http://purl.uniprot.org/uniprot/Q03145 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylates. Phosphorylated at Ser-898 by PKB; serum-induced phosphorylation which targets EPHA2 to the cell leading edge and stimulates cell migration. Phosphorylation by PKB is inhibited by EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal regulatory loop. Phosphorylated on tyrosine upon binding and activation by EFNA1. Phosphorylated residues Tyr-589 and Tyr-595 are required for binding VAV2 and VAV3 while phosphorylated residues Tyr-736 and Tyr-931 are required for binding PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3). These phosphorylated residues are critical for recruitment of VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream signaling to activate RAC1 GTPase and cell migration. Dephosphorylation of Tyr-931 by PTPRF prevents the interaction of EPHA2 with NCK1. Phosphorylated at Ser-898 in response to TNF by RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell migration. Phosphorylated at Ser-898 by PKA; blocks cell retraction induced by EPHA2 kinase activity. Dephosphorylated by ACP1.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Expressed in the lung, intestine and liver (PubMed:11287184). Expressed in myogenic progenitor cells (PubMed:27446912).|||First detected in gastrulation stage embryos (6.5-7.5 dpc) in ectodermal cells adjacent to the distal region of the primitive streak. By the neural plate stage (approximately 7.5 dpc), EPHA2 expression becomes restricted to the extreme distal end or node of the primitive streak. After the beginning of somitogenesis (approximately 8.0 dpc), expression persists in the node as this structure regresses toward the caudal end of the embryo. In addition, beginning at the mid head fold stage (approximately 7.75 dpc), we observe that EPHA2 exhibits a dynamic and spatially restricted expression pattern in the prospective hindbrain region. EPHA2 transcripts are initially detected in a 5-cell wide strip of mesodermal cells underlying prospective rhombomere 4 (R4). Subsequently at the beginning of somitogenesis, expression is observed in prospective R4. At the 4-8-somite stage, EPHA2 transcripts are observed in R4, mesenchymal cells underlying R4, and surface ectoderm in the vicinity of the developing second branchial arch. By the 10-somite stage, expression in these cells is down-regulated. Additionally, at the 5-8-somite stage, EPHA2 transcripts are detected initially in the lateral mesenchyme immediately underlying the surface ectoderm adjacent to R5 and R6, and subsequently in surface ectoderm overlying the developing third branchial arch. In myogenic progenitor cells, expressed during the acquisition of muscle stem cell properties, from 18.5 dpc to adulthood (PubMed:27446912).|||Homodimer. Interacts with INPPL1; regulates activated EPHA2 endocytosis and degradation (PubMed:29749928). Interacts (inactivated form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16, DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4 and may regulate tight junctions. Interacts with ACP1. Interacts with CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell migration and adhesion. Interacts with SLA. Interacts (phosphorylated form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3); critical for the EFNA1-induced activation of RAC1 which stimulates cell migration. Interacts with ANKS1A. Interacts with TIMD4 (By similarity).|||Mice are viable, fertile but exhibit aberrant development of tail vertebra and susceptibility to carcinogenesis.|||Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells (PubMed:29749928). Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.|||Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the HSP90 chaperone and regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation.|||focal adhesion|||lamellipodium membrane|||ruffle membrane http://togogenome.org/gene/10090:Vmn1r82 ^@ http://purl.uniprot.org/uniprot/Q8R283 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Drap1 ^@ http://purl.uniprot.org/uniprot/Q9D6N5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NC2 alpha/DRAP1 family.|||Heterodimer with DR1. Binds BTAF1 (By similarity).|||Nucleus|||Phosphorylation reduces DNA binding, but has no effect on heterodimerization and TBP binding.|||The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own (By similarity). http://togogenome.org/gene/10090:Cyp2c23 ^@ http://purl.uniprot.org/uniprot/E9Q5K4|||http://purl.uniprot.org/uniprot/Q3UEM4 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in polyunsaturated fatty acids (PUFAs) metabolism and signaling (PubMed:15084647). Catalyzes preferentially the epoxidation of double bonds of PUFAs (PubMed:15084647). Converts arachidonic acid (ARA, C20:4(n-6)) primarily to stereospecific products 8R,9S-epoxyeicosatrienoate (EET) and 11R,12S-EET (PubMed:15084647). Plays a major role in the formation of EETs and hydroxy-EETs (HEETs) in kidney. Via EETs may inhibit the epithelial sodium channels (ENaCs) in nephron segments, preventing excessive sodium absorption during high dietary salt intake (PubMed:24966089, PubMed:24368771). Participates in the formation of anti-inflammatory hydroxyepoxyeicosatrienoic acids (HEETs) by converting 20-hydroxyeicosatetraenoic acid (20-HETE) to 20,8,9-HEET, an activator of PPARA (By similarity). Metabolizes eicosapentaenoic acid (EPA, C20:5(n-3)) to epoxyeicosatetraenoic acid (EETeTr) regioisomers, 8,9-, 11,12-, 14,15-, and 17,18- EETeTr, preferentially producing 17R,18S enantiomer (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:15084647).|||Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases.|||Endoplasmic reticulum membrane|||Highly expressed in liver, particularly in hepatocytes and bile duct epithelial cells (at protein level) (PubMed:24966089). Expressed in nephron segments (PubMed:24966089, PubMed:15084647). Prominent expression is detected in proximal tubules at the corticomedullary junction (at protein level) (PubMed:15084647). Also expressed in renal cortical collecting duct (PubMed:15084647). Lower expression levels are detected in adrenal glands (PubMed:15084647).|||Microsome membrane|||Mutant mice have normal development and lack symptoms of disease or organ malformation (PubMed:24368771). Become hypertensive in response to high sodium or high potassium diets (PubMed:24368771, PubMed:24966089).|||Up-regulated by high sodium or high potassium diets. High sodium intake increases expression in thick ascending limb and distal convoluted tubule. An increase in dietary potassium intake induces expression in distal convoluted tubule and cortical collecting duct. http://togogenome.org/gene/10090:Noc2l ^@ http://purl.uniprot.org/uniprot/J3QK52|||http://purl.uniprot.org/uniprot/Q3UZI6 ^@ Similarity ^@ Belongs to the NOC2 family. http://togogenome.org/gene/10090:Sp2 ^@ http://purl.uniprot.org/uniprot/Q9D2H6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Binds to GC box promoters elements and selectively activates mRNA synthesis from genes that contain functional recognition sites.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP2, the motif is inactive. http://togogenome.org/gene/10090:Mrgprh ^@ http://purl.uniprot.org/uniprot/Q99MT8|||http://purl.uniprot.org/uniprot/W8W3M0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Membrane|||Orphan receptor. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Slc16a4 ^@ http://purl.uniprot.org/uniprot/Q8R0M8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate (By similarity). http://togogenome.org/gene/10090:Toe1 ^@ http://purl.uniprot.org/uniprot/Q9D2E2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAF1 family.|||Inhibits cell growth rate and cell cycle. Induces CDKN1A expression as well as TGF-beta expression. Mediates the inhibitory growth effect of EGR1. Involved in the maturation of snRNAs and snRNA 3'-tail processing.|||Interacts with U1, U2, U4, U5 and U6 snRNAs.|||Nucleus speckle|||nucleolus http://togogenome.org/gene/10090:Taar7e ^@ http://purl.uniprot.org/uniprot/A6H6B4|||http://purl.uniprot.org/uniprot/Q5QD09 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Spred3 ^@ http://purl.uniprot.org/uniprot/Q6P6N5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain specific.|||Cell membrane|||Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction leads to palmitoylation of SPRED3.|||Palmitoylated by ZDHHC17/HIP14.|||Phosphorylated on tyrosine.|||Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase (PubMed:12646235). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (PubMed:29501879). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (PubMed:25576668).|||Ubiquitinated. http://togogenome.org/gene/10090:Map1lc3a ^@ http://purl.uniprot.org/uniprot/Q91VR7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3 different light chains, LC1, LC2 and LC3, can associate with MAP1A and MAP1B proteins (By similarity). Interacts with TP53INP1 and TP53INP2 (By similarity). Directly interacts with SQSTM1; this interaction leads to MAP1LC3A recruitment to inclusion bodies containing polyubiquitinated protein aggregates and to inclusion body degradation by autophagy (By similarity). Interacts with ATG13 (By similarity). Interacts with ULK1 (By similarity). Interacts with TBC1D5 (By similarity). Found in a complex with UBQLN1 and UBQLN2 (By similarity). Interacts with UBQLN4 (via STI1 1 and 2 domains) (By similarity). Interacts with UBQLN1 in the presence of UBQLN4 (By similarity). Interacts with TRIM5 (By similarity). Interacts with MEFV (By similarity). Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3 (PubMed:34338405). Interacts with PICALM (By similarity). Interacts with the reticulophagy receptor TEX264 (By similarity). Interacts with MOAP1 (via LIR motif) (By similarity). Interacts with Irgm1 (By similarity).|||Belongs to the ATG8 family.|||Endomembrane system|||Phosphorylation at Ser-12 by PKA inhibits conjugation to phosphatidylethanolamine (PE).|||The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, LC3-I (PubMed:12207896, PubMed:14530254). The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, LC3-II (By similarity). During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid (By similarity). ATG4 proteins also mediate the delipidation of PE-conjugated forms (PubMed:33795848). In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy (By similarity). ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (PubMed:33795848).|||Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover.|||autophagosome|||autophagosome membrane|||cytoskeleton http://togogenome.org/gene/10090:Spns2 ^@ http://purl.uniprot.org/uniprot/Q91VM4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.|||Cell membrane|||Deficient mice are viable, do not exhibit cardiac defects or embryonic lethality, and are generally normal and fertile (PubMed:22664872, PubMed:22406534). Deficient mice have decreased levels of sphingosine 1-phosphate (S1P) and dihydro-S1P in blood, accompanied by increases in very long chain ceramide species, and have defective lymphocyte trafficking (PubMed:22664872, PubMed:22406534, PubMed:23180825). S1P levels are increased in lymph from deficient mice as well as in specific tissues, including lymph nodes, and interstitial fluid (PubMed:23180825). Moreover, these mice have aberrant lymphatic sinus that appeared collapsed, with reduced numbers of lymphocytes (PubMed:23180825). Mice display marked accumulation of mature T-cells in thymus and decreased numbers of peripheral T-cells in blood and secondary lymphoid organs (PubMed:22406534, PubMed:34260944). Mature recirculating B-cells are reduced in frequency in the bone marrow as well as in blood and secondary lymphoid organs (PubMed:22406534). Mice do not show defects in S1P release from blood cells (PubMed:22406534). Knockout mice are protected against experimental autoimmune encephalomyelitis (PubMed:34260944). Mutants also show a profound hearing impairment, characterized by a progressive degeneration of sensory hair cells in the organ of Corti (PubMed:25356849, PubMed:30973865). Hearing loss is caused by a decline in the endocochlear potential (PubMed:25356849). Conditional deletion in the cochlea causes early onset progressive hearing loss (PubMed:25356849). In contrast, hearing impairment is not observed in mice with targeted deletion in red blood cells, platelets, lymphatic or vascular endothelial cells (PubMed:25356849).|||Endosome membrane|||Expression is high in the lungs and liver, low in the lymph nodes, spleen and bone marrow, and very low but detectable in the thymus (PubMed:22664872). Not expressed in red blood cells (PubMed:23103166). Also expressed in the inner ear: expressed in the cochlea, both in the lateral wall and organ of Corti (PubMed:25356849).|||Lipid transporter that specifically mediates export of sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and sphinganine-1-phosphate in the lymph, thereby playing a role in lymphocyte trafficking (PubMed:22664872, PubMed:23103166, PubMed:22406534, PubMed:23180825, PubMed:34260944). S1P is a bioactive signaling molecule that regulates many physiological processes important for the development and for the immune system (PubMed:22664872, PubMed:23103166, PubMed:22406534, PubMed:23180825, PubMed:34260944). Regulates levels of S1P and the S1P gradient that exists between the high circulating concentrations of S1P and low tissue levels that control lymphocyte trafficking (PubMed:22664872, PubMed:22406534, PubMed:23180825, PubMed:34260944). Required for the egress of T-cells from lymph nodes during an immune response by mediating S1P secretion, which generates a gradient that enables activated T-cells to access lymph (PubMed:22406534, PubMed:34260944). Also required for the egress of immature B-cells from the bone marrow (PubMed:22406534). In contrast, it does not mediate S1P release from red blood cells (PubMed:23103166, PubMed:22406534). Involved in auditory function: S1P release in the inner ear is required for maintenance of the endocochlear potential in the cochlea (PubMed:25356849). In addition to export, also able to mediate S1P import (PubMed:33785361). http://togogenome.org/gene/10090:Whrn ^@ http://purl.uniprot.org/uniprot/Q80VW5 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, expressed in the basal plate of the spinal cord, in the ventralneural epithelium of the developing brain and in the region of the lung bud. At 12.5 dpc, expressed in the complete neuroepithelium except for the neocortex. In the developing eye, expressed in the inner neuroblastic layer. At 14.5 dpc, detected in the intervertebral cartilage, the cortex of the developing kidney, the tongue, the region of the urethra and strongly in specific regions of the brain, e.g. striatum, optic recess, ventral tegmental area, roof of the midbrain, choroid plexus of the lateral ventricles and the fourth ventricle. The developing neocortex is devoid of expression. At this timepoint, expression is first notable in the inner ear in the developing maculae of the saccule and the utricle, in the cristae of the semicircular canals and in the vestibulocochlear ganglion. In the developing neural retina, a strong signal is present in the inner neuroblastic layer. At 16.5 dpc, expression is very similar to that at 14.5 dpc. At 18.5 dpc, expression is mainly as in 16.5 dpc. Expression in the ganglion layers of the retina decreases and is no longer detected in the innermost region of these layers. From postnatal day 7 (P7) onwards, also the developing photoreceptor cells express whirlin (PubMed:16434480). Expression decreases by 11 days after birth in inner ear hair cells and by 14 days after birth in outer ear hair cells. Expressed in vestibular hair cells at high levels through to adulthood.|||Cytoplasm|||Defects in Whrn are the cause of the phenotype whirler (wi). Mutants are characterized by deafness due to malformation of the cochlear inner and outer hair cells and by circling behavior. Stereocilia are shorter and wider than in wild-type animals and there is a decrease in the number of actin filaments in inner and outer hair cells. The number of outer hair cell stereocilia is reduced with increased spacing between them.|||Expressed in the retina. Colocalizes with RPGR in the photoreceptor connecting cilium, a thin bridge linking the cell body and the light-sensing outer segment (at protein level). Detected in the inner ear throughout development from embryonic day 12 to 20 days after birth. Displays a dynamic pattern of expression after birth, demonstrating an ordered appearance and fade-out across stereocilia rows. Isoforms 5, 6, 7 and 8 are not detected in the retina (PubMed:20502675).|||Forms homooligomers (PubMed:15590698, PubMed:25406310). Interacts (via C-terminal PDZ domain) with MYO15A; this interaction is necessary for localization of WHRN to stereocilia tips (PubMed:15654330, PubMed:15590698). Interacts (via C-terminal PDZ domain) with MPP1/p55 (PubMed:16829577, PubMed:17584769). Interacts with LRRC4C/NGL1 (PubMed:15590698). Interacts with MYO7A (PubMed:15590698). Interacts with RPGR (PubMed:22323458). Interacts with EPS8 (PubMed:21236676). Interacts with CASK. Interacts with CIB2 (By similarity). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN (PubMed:20502675, PubMed:25406310). Interacts (via PDZ domains) with PDZD7; the interaction is direct (PubMed:25406310). Interacts (via N-terminal PDZ domain) with USH2A (via cytoplasmic region) (PubMed:16301217, PubMed:20502675, PubMed:23055499). Interacts with ADGRV1/MASS1 (via cytoplasmic region) (PubMed:20502675, PubMed:23055499).|||Involved in hearing and vision as member of the USH2 complex (PubMed:20502675). Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear (PubMed:15590699). Involved in the maintenance of the hair bundle ankle region, which connects stereocilia in cochlear hair cells of the inner ear (PubMed:20502675, PubMed:24334608). In retina photoreceptors, required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport (PubMed:20502675).|||Major isoform.|||May be due to intron retention.|||Mutant mice for isoform 1 appear viable and comparable to their wild-type littermates in growth characteristics, reproductive performance and general health (PubMed:20502675). At 2 and 9 months of age, knockouts show a profound hearing loss across all cochlear frequencies (PubMed:20502675). At 28 to 33 months, they show signs for retinal degeneration such as a thinner photoreceptor nuclear layer and outer segments shortened (PubMed:20502675).|||Photoreceptor inner segment|||Synapse|||growth cone|||stereocilium http://togogenome.org/gene/10090:Enoph1 ^@ http://purl.uniprot.org/uniprot/Q8BGB7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAD-like hydrolase superfamily. MasA/MtnC family.|||Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), which is then dephosphorylated to form the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene).|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Monomer.|||Nucleus http://togogenome.org/gene/10090:Brix1 ^@ http://purl.uniprot.org/uniprot/Q9DCA5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BRX1 family.|||Required for biogenesis of the 60S ribosomal subunit.|||nucleolus http://togogenome.org/gene/10090:Dtx2 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZY1|||http://purl.uniprot.org/uniprot/Q8R3P2 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Deltex family.|||Cytoplasm|||Expressed in testis and the CNS.|||Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1.|||In the CNS, it is expressed in the developing neural tube starting from 10.5 dpc in the spinal cord and around 11.5 dpc in the telencephalon. Expressed ubiquitously throughout the spinal cord and telencephalon during neurogenesis. Expressed throughout the developing retina at 15.5 dpc. Not expressed in the somite or presomite during somitogenesis. Expressed slightly earlier that Dtx1 and Dtx3.|||Nucleus|||Recurrent site of retroviral integration in murine B-cell lymphomas.|||Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity (By similarity).|||Splicing donor site not canonical.|||The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases. http://togogenome.org/gene/10090:Aldh2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JEU1|||http://purl.uniprot.org/uniprot/P47738|||http://purl.uniprot.org/uniprot/Q544B1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldehyde dehydrogenase family.|||By retinoic acid; 3-5 fold increase.|||Homotetramer.|||Mitochondrion matrix|||Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage. http://togogenome.org/gene/10090:Mettl25 ^@ http://purl.uniprot.org/uniprot/Q6NXH8 ^@ Function ^@ Probable methyltransferase. http://togogenome.org/gene/10090:Ubald1 ^@ http://purl.uniprot.org/uniprot/Q6P3B2 ^@ Similarity ^@ Belongs to the UBALD family. http://togogenome.org/gene/10090:Nuggc ^@ http://purl.uniprot.org/uniprot/D3YWJ0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ B-cell and T-cell development is unaffected, and germinal centers form normally. Class-switch recombination in B-cells is not affected. B-cells in older mice (3 months onwards) show significantly increased somatic hypermutation near the immunoglobulin heavy chain locus, mainly at G:C base pairs. Other loci also show increased rates of somatic hypermutation.|||Nuclear GTPase found in germinal center B-cells, where it may inhibit function of the activation-induced cytidine deaminase AICDA (By similarity). Reduces somatic hypermutation in B-cells which may enhance genome stability (PubMed:22833677).|||Nucleus speckle http://togogenome.org/gene/10090:Psmd3 ^@ http://purl.uniprot.org/uniprot/P14685 ^@ Function|||Similarity|||Subunit ^@ Belongs to the proteasome subunit S3 family.|||Component of the 19S proteasome regulatory particle complex (PubMed:16857966). The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (By similarity). The regulatory particle is made of a lid composed of 9 subunits including PSMD3, a base containing 6 ATPases and few additional components (By similarity). Interacts with UBQLN1 (via ubiquitin-like domain) (By similarity). Interacts with ERCC6 (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. http://togogenome.org/gene/10090:Or2t43 ^@ http://purl.uniprot.org/uniprot/M9MMJ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppp1r15b ^@ http://purl.uniprot.org/uniprot/Q8BFW3 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the PPP1R15 family.|||Interacts with PP1. Part of a complex containing PPP1R15B, PP1 and NCK1/2.|||Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1.|||Mice are born at the expected Mendelian ratio, but exhibit severe growth retardation and impaired erythropoiesis. None survive the first day of postnatal life. PPP1R15A-PPP1R15B double-knockout embryos do not develop past the preimplantation period. http://togogenome.org/gene/10090:Gpr158 ^@ http://purl.uniprot.org/uniprot/Q8C419 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Expression in the dentate gyrus is regulated by RBBP4 (PubMed:30355501). Strongly up-regulated in the prefrontal cortex in response to stress (PubMed:29419376). Down-regulated in the hippocampus in response to hyperglycemia (PubMed:36634900).|||Highly expressed in brain (PubMed:29419376, PubMed:36979415). Expressed in several brain regions including the cerebral cortex, hippocampus, cerebellum and caudate putamen (PubMed:36979415). Only expressed in neurons, and not in microglia, oligodendrocytes or astrocytes (PubMed:36979415). Expressed in the visual center of the cerebral cortex (PubMed:30855200). Also expressed in the eye, including photoreceptors, ganglion cells and trabecular meshwork (PubMed:30855200).|||Homodimer (By similarity). Associates with the RGS7-GNB5 complex, promoting its localization to the cell membrane and regulating its GTPase activator activity (PubMed:22689652, PubMed:25792749, PubMed:31311860). Interacts (via VCPWE motifs) with GNAO1 (PubMed:25792749). Interacts with GPC4 (By similarity). Interacts with EGFLAM (PubMed:30282023).|||Metabotropic receptor for glycine that controls synapse formation and function in the brain (PubMed:29419376, PubMed:31749686, PubMed:31311860, PubMed:36996198). Acts as an atypical G-protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins (PubMed:22689652, PubMed:25792749, PubMed:31311860, PubMed:30546127). In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (By similarity). Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels (By similarity). Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity (By similarity). Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (PubMed:31311860, PubMed:36996198). Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (PubMed:28851741, PubMed:29419376, PubMed:31749686, PubMed:31311860, PubMed:30546127). Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability (PubMed:31749686). Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4 (PubMed:30290982). In addition to glycine, may also act as a receptor for osteocalcin (Bglap or Bglap2) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (PubMed:28851741, PubMed:30355501).|||Mice show prominent antidepressant-like phenotype and stress resilience, characterized by attenuated response to stress-induced hyperthermia (PubMed:29419376). Mice also display defects in spatial learning and decreased acquisition of safety learning (PubMed:31749686). Mice show a short-term protection against the intraocular pressure increase that occurred with aging; however this protection is reversed over time (PubMed:30855200).|||Nucleus|||Postsynaptic cell membrane|||Presynaptic cell membrane|||The Cache-like region shares similarity with the Cache domain, a well-known receptor for amino acids (By similarity). It acts as a ligand-binding module that recognizes and binds glycine and taurine (By similarity). http://togogenome.org/gene/10090:Fastkd1 ^@ http://purl.uniprot.org/uniprot/Q6DI86 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAST kinase family.|||Expression detected in spleen, testis, colon, heart, smooth muscle, kidney, brain, lung, liver, brown and white adipose tissue with highest expression in heart and brown adipose tissue.|||Involved in the down-regulation of mitochondrial MT-ND3 mRNA levels which leads to decreased respiratory complex I abundance and activity.|||Mitochondrion|||The RAP domain is essential to regulate MT-ND3 mRNA levels. http://togogenome.org/gene/10090:Pkp3 ^@ http://purl.uniprot.org/uniprot/Q9QY23 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-catenin family.|||May play a role in junctional plaques.|||Nucleus|||desmosome http://togogenome.org/gene/10090:Slc35e3 ^@ http://purl.uniprot.org/uniprot/Q6PGC7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPT transporter family. SLC35E subfamily.|||Membrane|||Putative transporter. http://togogenome.org/gene/10090:Gsta5 ^@ http://purl.uniprot.org/uniprot/E9Q6L7 ^@ Similarity ^@ Belongs to the GST superfamily. Alpha family. http://togogenome.org/gene/10090:Gfi1 ^@ http://purl.uniprot.org/uniprot/P70338 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ By IL2 and CSF3. Induced by the endotoxin bacterial lipopolysaccharide (LPS) in primary bone marrow macrophages (BMDMs).|||Interacts (via the zinc-finger domain) with ARIH2; the interaction prevents GFI1 ubiquitination and proteasomal degradation. Forms a complex with EHMT2 and HDAC1 to promote 'Lys-9' dimethylation of H3 (H3K9Me2) and repress expression of target genes. Interacts directly with EHMT2. Interacts with RUNX1T1; the interaction represses HDAC-mediated transcriptional activity. Interacts (via the C-terminal zinc fingers) with ZBTB17; the interaction results in the recruitment of GFI1 to the CDKN1A/p21 and CDKNIB promoters and repression of transcription (By similarity). Interacts with U2AF1L4. Component of RCOR-GFI-KDM1A-HDAC complexes. Interacts directly with RCOR1, KDM1A and HDAC2. Also interacts with HDAC1. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly with AJUBA (via its LIM domains); the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes and, occurs independently of the SNAG domain. Interacts with SPI1; the interaction inhibits SPI1 transcriptional activity targeted at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (PubMed:17197705). Interacts with PIAS3; the interaction relieves the inhibitory effect of PIAS3 on STAT3-mediated transcriptional activity. Interacts with RELA; the interaction occurs on liposaccharide (LPS) stimulation and controls RELA DNA binding activity and regulates endotoxin-mediated TOLL-like receptor inflammatory response.|||Nucleus|||Null mice exhibit neutropenia, characterized by absence of neutrophils. This results in growth retardation, susceptibility to bacterial infection and early lethality. Immature granulocytes and macrophage precursors accumulate in bone marrow. Mice have inner ear anomalies, as they are ataxic, circle, display head tilting behavior and do not respond to noise. In the inner ear, hair cells are disorganized in both vestibule and cochlea. Outer hair cells of the cochlea are initially improperly innervated, and just before birth, mice lose all cochlear hair cells due to apoptosis. By 5 months there is a dramatic reduction in the number of cochlear neurons.|||The SNAG domain of GFIs is required for nuclear location and for interaction with some corepressors.|||Transcription repressor essential for hematopoiesis. Functions in a cell-context and development-specific manner. Binds to 5'-TAAATCAC[AT]GCA-3' in the promoter region of a large number of genes. Component of several complexes, including the EHMT2-GFI1-HDAC1, AJUBA-GFI1-HDAC1 and RCOR-GFI-KDM1A-HDAC complexes, that suppress, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Regulates neutrophil differentiation, promotes proliferation of lymphoid cells, and is required for granulocyte development (PubMed:17197705). Inhibits SPI1 transcriptional activity at macrophage-specific genes, repressing macrophage differentiation of myeloid progenitor cells and promoting granulocyte commitment (PubMed:17197705). Mediates, together with U2AF1L4, the alternative splicing of CD45 and controls T-cell receptor signaling. Regulates the endotoxin-mediated Toll-like receptor (TLR) inflammatory response by antagonizing RELA (PubMed:20547752). Cooperates with CBFA2T2 to regulate ITGB1-dependent neurite growth. Controls cell-cycle progression by repressing CDKNIA/p21 transcription in response to TGFB1 via recruitment of GFI1 by ZBTB17 to the CDKNIA/p21 and CDKNIB promoters. Required for the maintenance of inner ear hair cells (PubMed:12441305).|||Ubiquitinated.|||Zinc fingers 3,4 and 5 are required for DNA binding and for interaction with SPI1. http://togogenome.org/gene/10090:Nepro ^@ http://purl.uniprot.org/uniprot/Q8R2U2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the nepro family.|||Expressed in all blastomeres at the 8-cell stage (PubMed:26178919). Detected in the ventricular zone (VZ) of the forebrain at 9.5 dpc. Clearly detected until 12.5 dpc, the expression decreases and disappears by 15.5 dpc (PubMed:19906856).|||Knockout embryos die before preimplantation.|||May play a role in cortex development as part of the Notch signaling pathway. Downstream of Notch may repress the expression of proneural genes and inhibit neuronal differentiation thereby maintaining neural progenitors (PubMed:19906856). May also play a role in preimplentation embryo development (PubMed:26178919).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Gpsm2 ^@ http://purl.uniprot.org/uniprot/Q3UPG3|||http://purl.uniprot.org/uniprot/Q8VDU0 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GPSM family.|||Cytoplasm|||Detected in brain and liver (at protein level). Detected in brain, spleen, liver and testis, and at lower levels in heart, lung and kidney. Enriched in the ventricular zone of the developing central nervous systems (PubMed:12571286). Expressed in proximal colon, ileum, ovary, Sertoli cells of the testis and granular cells within the cerebellum (PubMed:31112734).|||Each GoLoco domain can bind one GNAI3 (PubMed:22952234). In the auto-inhibited conformation, the GoLoco domains interact with the TPR repeat region (PubMed:23665171).|||Interacts with the dynein-dynactin complex; this interaction is inhibited in a PLK1-dependent manner (By similarity). Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (By similarity). Interacts with LLGL2 (By similarity). Interacts (via TPR repeat region) with INSC/inscuteable (PubMed:16094321, PubMed:21816348). Interacts (via TPR repeat region) with NUMA1 (via C-terminus); this interaction is direct, inhibited in a PLK1-dependent manner and promotes spindle pole organization (PubMed:21816348, PubMed:23318951, PubMed:23665171). INSC and NUMA1 compete for the same binding site, but INSC has higher affinity and can displace NUMA1 (in vitro) (PubMed:21816348). Interacts with GNAI2 (By similarity). Interacts (via GoLoco domains) with the GDP-bound form of GNAI1 and GNAI3; has much lower affinity for the GTP-bound form (PubMed:22952234, PubMed:23665171). Interaction with GDP-bound GNAI3 strongly enhances the affinity for NUMA1 (PubMed:23665171). Interacts (via TPR repeat region) with FRMPD1 (PubMed:23318951). INSC and FRMPD1 compete for the same binding site, but INSC has higher affinity and can displace FRMPD1 (in vitro) (PubMed:23318951). Interacts (via TPR repeat region) with FRMPD4. Identified in a complex with INSC and F2RL2/Par3 (By similarity). Interacts with TASOR (PubMed:31112734).|||It is uncertain whether Met-1 or Met-8 is the initiator.|||Lateral cell membrane|||Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:21816348). Required for cortical dynein-dynactin complex recruitment during metaphase (By similarity). Plays a role in metaphase spindle orientation (By similarity). Plays an important role in asymmetric cell divisions (PubMed:12571286, PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their activity (PubMed:22952234).|||cell cortex|||spindle pole http://togogenome.org/gene/10090:Zc3h12d ^@ http://purl.uniprot.org/uniprot/E9QNR7|||http://purl.uniprot.org/uniprot/Q8BIY3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZC3H12 family.|||Cytoplasm|||Expressed at low levels in bone marrow derived macrophages.|||Interacts with ZC3H12A.|||May regulate cell growth likely by suppressing RB1 phosphorylation (By similarity). May function as RNase and regulate the levels of target RNA species (Potential). In association with ZC3H12A enhances the degradation of interleukin IL-6 mRNA level in activated macrophages (PubMed:26134560). Serve as a tumor suppressor in certain leukemia cells (By similarity). Overexpression inhibits the G1 to S phase progression through suppression of RB1 phosphorylation (By similarity).|||P-body http://togogenome.org/gene/10090:Fmn1 ^@ http://purl.uniprot.org/uniprot/A0A5F8MPL0|||http://purl.uniprot.org/uniprot/E9Q7P6|||http://purl.uniprot.org/uniprot/Q05860 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the formin homology family. Cappuccino subfamily.|||Cell membrane|||Cytoplasm|||Interacts with alpha-catenin and may interact with tubulin.|||It is present in the adult kidney, testis, limb, ovary, brain, small intestine, salivary gland and harderian gland. Isoforms 1, 2 and 5 are detected in skin and keratinocytes. Isoform 5 is found throughout the embryo.|||It is present throughout the embryo. In the developing limb bud, the protein is expressed in the apical ectodermal ridge and the mesenchymal compartment, predominantly in the posterior region. During kidney morphogenesis, expression is initially restricted to the epithelial compartment of the pronephros and mesonephros. Isoform 5 is found in the apical ectodermal ridge and the mesenchymal compartment of the developing limb bud.|||Nucleus|||Phosphorylated on serine and possibly threonine residues.|||Plays a role in the formation of adherens junction and the polymerization of linear actin cables.|||Was originally thought to play a role in limb bud development based on the fact that limb deformity (ld) mutants are associated with Fmn1 gene disruption. However, PubMed:15198975 shows that limb deformity mutations rather affects Grem1 cis-regulatory regions localized in Fmn1 gene and that loss of Grem1 (gremlin-1) expression is the cause of limb malformations.|||adherens junction|||cytoskeleton http://togogenome.org/gene/10090:P2rx4 ^@ http://purl.uniprot.org/uniprot/D3YYR5|||http://purl.uniprot.org/uniprot/D3Z5U5|||http://purl.uniprot.org/uniprot/Q9Z256|||http://purl.uniprot.org/uniprot/Q9Z257 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the P2X receptor family.|||Functional P2XRs are organized as homomeric and heteromeric trimers.|||Membrane|||Receptor for ATP that acts as a ligand-gated ion channel. http://togogenome.org/gene/10090:Bpifb4 ^@ http://purl.uniprot.org/uniprot/A2BGH0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||Cytoplasm|||May have the capacity to recognize and bind specific classes of odorants. May act as a carrier molecule, transporting odorants across the mucus layer to access receptor sites. May serve as a primary defense mechanism by recognizing and removing potentially harmful odorants or pathogenic microorganisms from the mucosa or clearing excess odorant from mucus to enable new odorant stimuli to be received (By similarity).|||Secreted http://togogenome.org/gene/10090:Lrmda ^@ http://purl.uniprot.org/uniprot/Q9D9B4 ^@ Function ^@ Required for melanocyte differentiation. http://togogenome.org/gene/10090:Tdgf1 ^@ http://purl.uniprot.org/uniprot/P51865|||http://purl.uniprot.org/uniprot/Q3UZP8 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.|||Cell membrane|||Expressed at low level in specific organs of the adult animal such as spleen, heart, lung and brain. During gastrulation, expressed in the forming mesoderm. In later stages of the developing heart, expression is restricted to the truncus arteriosus.|||First expressed prior to the onset of gastrulation (early streak stage), then continues throughout embryonic development.|||GPI-anchored cell membrane protein involved in Nodal signaling. Cell-associated CRIPTO acts as a Nodal coreceptor in cis. Shedding of CRIPTO by Tmem8a modulates Nodal signaling by allowing soluble CRIPTO to act as a Nodal coreceptor on other cells. Could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm.|||Interacts with the activin type-1 receptor ACVR1B.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||The GPI-anchor is attached to the protein in the endoplasmic reticulum and serves to target the protein to the cell surface. There, it is processed by GPI processing phospholipase A2 (Tmem8a), removing an acyl-chain at the sn-2 position of GPI and releasing CRIPTO as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D (Gpld1) into a soluble form. http://togogenome.org/gene/10090:Slc6a20b ^@ http://purl.uniprot.org/uniprot/A0A803YV45|||http://purl.uniprot.org/uniprot/O88575 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A20 subfamily.|||Detected only in kidney and lung.|||Does not show transporter activity with a range of tested amino acids including proline, glutamine, glutamic acid, leucine, alanine, histidine, glycine and arginine.|||Interacts with CLTRN.|||Membrane http://togogenome.org/gene/10090:Mlxip ^@ http://purl.uniprot.org/uniprot/Q2VPU4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds DNA as a heterodimer with MLX and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation.|||Broadly expressed from 9.5 dpc to at least 15 dpc, with slightly elevated levels in the developing nervous system.|||Cytoplasm|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer with MLX.|||Mitochondrion outer membrane|||Nucleus http://togogenome.org/gene/10090:Alkal2 ^@ http://purl.uniprot.org/uniprot/Q80UG6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ALKAL family.|||Cell membrane|||Cytokine that acts as a physiological ligand for receptor tyrosine kinases LTK and ALK, leading to their activation. Cytokine-binding is sufficient to activate LTK. In contrast, ALKAL2-driven activation of ALK is coupled with heparin-binding to ALK. Stimulation of ALK signaling is involved in neural development and regulation of energy expenditure.|||Homodimer.|||Secreted http://togogenome.org/gene/10090:Ythdf3 ^@ http://purl.uniprot.org/uniprot/Q8BYK6 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the YTHDF family. YTHDF3 subfamily.|||Interacts with CNOT1; promoting recruitment of the CCR4-NOT complex (By similarity). Interacts with YTHDF1 (By similarity). Interacts with YTHDF2 (By similarity). Interacts with PAN3 (PubMed:32905781).|||Mice are viable and normal in size but display increased interferon-stimulated genes (ISGs) levels and are resistant to several viral infections (PubMed:30591559). Mice lacking Ythdf1, Ythdf2 and Ythdf3 display early embryonic lethality and show defects in embryonic stem cell differentiation (PubMed:32943573).|||P-body|||Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:32905781, PubMed:32943573). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:32943573). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT complex or PAN3 (PubMed:32943573, PubMed:32905781). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:32943573). Acts as a negative regulator of type I interferon response by down-regulating interferon-stimulated genes (ISGs) expression: acts by binding to FOXO3 mRNAs (PubMed:30591559). Binds to FOXO3 mRNAs independently of METTL3-mediated m6A modification (PubMed:30591559). Can also act as a regulator of mRNA stability in cooperation with YTHDF2 by binding to m6A-containing mRNA and promoting their degradation (By similarity). Recognizes and binds m6A-containing circular RNAs (circRNAs); circRNAs are generated through back-splicing of pre-mRNAs, a non-canonical splicing process promoted by dsRNA structures across circularizing exons (By similarity). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (By similarity). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (By similarity). May also recognize and bind N1-methyladenosine (m1A)-containing mRNAs: inhibits trophoblast invasion by binding to m1A-methylated transcripts of IGF1R, promoting their degradation (By similarity).|||Stress granule|||The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues. This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons.|||Was initially reported to act as a regulator of mRNA translation efficiency by binding to m6A-containing mRNAs (PubMed:30591559). This study suggested that the 3 different paralogs (YTHDF1, YTHDF2 and YTHDF3) have unique functions with limited redundancy (PubMed:32943573). However, later studies showed that YTHDF1, YTHDF2 and YTHDF3 paralogs have redundant functions to a profound extent and directly promote degradation of m6A-containing mRNAs (PubMed:32943573). The effect on translation efficiency observed earlier is probably indirect (PubMed:32943573).|||cytosol http://togogenome.org/gene/10090:Col13a1 ^@ http://purl.uniprot.org/uniprot/Q9R1N9 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Expression levels remain fairly constant during early fetal development. This is followed by a marked increase of expression levels during the final stages of organogenesis, with initiation of the rapid fetal growth phase before birth. At mid-gestation, strongly expressed in the central and peripheral nervous systems. Also strongly expressed in developing heart, with localization to cell-cell contacts and accentuated in intercalated disks perinatally. During late fetal development, expressed in many tissues including cartilage, bone, skeletal muscle, lung, intestine and skin. Not detected in endothelia of most blood vessels or the endocardium of the heart.|||Homotrimer; disulfide-linked. Nucleation of the type XIII collagen triple helix is likely to occur at the N-terminal region with triple helix formation proceeding from the N- to the C-terminus. Interacts with FN1, perlecan/HSPG2 and NID2 (By similarity).|||Involved in cell-matrix and cell-cell adhesion interactions that are required for normal development. May participate in the linkage between muscle fiber and basement membrane. May play a role in endochondral ossification of bone and branching morphogenesis of lung. Binds heparin. At neuromuscular junctions, may play a role in acetylcholine receptor clustering (PubMed:26626625).|||Postsynaptic cell membrane|||Transgenic mice overexpressing COL13A1 with a 90 amino acid in-frame deletion of the COL2 sequence show embryonic lethality due either to a lack of placental formation or to cardiovascular defects in offspring from heterozygous mating. In contrast, transgenic mice expressing an N-terminally altered COL13A1 lacking both cytosolic and transmembrane domains while retaining the collagenous ectodomain are viable and fertile, but display progressive muscular myopathy. http://togogenome.org/gene/10090:Caskin1 ^@ http://purl.uniprot.org/uniprot/Q6P9K8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds the CaM kinase domain of CASK. Forms a ternary complex with CASK and LIN7A, LIN7B or LIN7C. Competes with APBA1 that forms a similar complex with CASK and LIN7 proteins. The tripartite complex CASKIN1/CASK/LIN7(A/B/C) binds the cytoplasmic tail of NRXN1. Polymerizes, via the tandem SAM domains, to form long, 8 nM wide fibers, upon which other proteins can assemble (By similarity).|||Cytoplasm|||May link the scaffolding protein CASK to downstream intracellular effectors. http://togogenome.org/gene/10090:Timmdc1 ^@ http://purl.uniprot.org/uniprot/Q8BUY5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the intermediate 315 kDa subcomplex of incompletely assembled complex I. Interacts with TMEM70 (By similarity).|||Belongs to the Tim17/Tim22/Tim23 family.|||Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Participates in constructing the membrane arm of complex I (By similarity).|||Mitochondrion membrane http://togogenome.org/gene/10090:Lrfn1 ^@ http://purl.uniprot.org/uniprot/Q2WF71 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRFN family.|||Can form heteromeric complexes with LRFN2, LRFN3, LRFN4 and LRFN5. Forms homomeric complexes, but not across cell junctions. Interacts with DLG4. Interacts also with DLG1, DLG2, and DLG3 (By similarity). Interacts with 2 AMPA receptor subunits GRIA1 and GRIA2 and NMDA receptor subunit GRIN1.|||Expression starts around 10.5 dpc. At 11.5 dpc, broadly expressed in the telencephalic and diencephalic vesicles. This pattern of expression continues until 17.5 dpc.|||Glycosylated.|||Membrane|||Postsynaptic density membrane|||Predominantly expressed in the brain, with a weak, but broad expression in the cerebral cortex and diencephalic nuclei. Also detected in other parts of the central nervous system, including the olfactory bulb, pons, cerebellum, and medulla oblongata, as well as in the peripheral nervous system, such as the ganglia of cranial nerves and the dorsal root ganglion during gestation.|||Promotes neurite outgrowth in hippocampal neurons. Involved in the regulation and maintenance of excitatory synapses. Induces the clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1, GRIA1 and GRIN1.|||Synapse|||The PDZ-binding motif is required for neurite outgrowth promotion. This motif is also involved in DLG1-, DLG3- and DLG4-binding (By similarity). http://togogenome.org/gene/10090:Ticrr ^@ http://purl.uniprot.org/uniprot/Q8BQ33 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the treslin family.|||Interacts with TOPBP1 (via BRCT domains); interaction takes place in a CDK2-dependent manner (By similarity). Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR (By similarity).|||Nucleus|||Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation (By similarity). http://togogenome.org/gene/10090:Bcl10 ^@ http://purl.uniprot.org/uniprot/Q9Z0H7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Detected in developing brain, olfactory epithelium, tongue, whisker follicles, salivary gland, heart, lung, liver and intestinal epithelia of stage 15 embryos.|||Homomultimer; homooligomerized following recruitment by CARD domain-containing proteins that form a nucleating helical template that recruits BCL10 via CARD-CARD interaction (By similarity). Self-associates by CARD-CARD interaction and interacts with other CARD-proteins such as CARD9, CARD10, CARD11 and CARD14 (PubMed:22265677, PubMed:22880103). Forms a complex with CARD14 and MALT1; resulting in the formation of a CBM (CARD14-BCL10-MALT1) complex (By similarity). Forms a complex with CARD11 and MALT1; resulting in the formation of a CBM (CARD11-BCL10-MALT1) complex (By similarity). Forms a complex with CARD9 and MALT1; resulting in the formation of a CBM (CARD9-BCL10-MALT1) complex (PubMed:22265677). Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (By similarity). Binds caspase-9 with its C-terminal domain (By similarity). Interacts with TRAF2 and BIRC2/c-IAP2 (By similarity). Interacts with PELI2 and SOCS3; these interactions may be mutually exclusive (PubMed:15213237).|||Membrane raft|||Phosphorylated by IKBKB/IKKB.|||Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation (PubMed:22265677). Acts by channeling adaptive and innate immune signaling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:22265677). Recruited by activated CARD domain-containing proteins: homooligomerized CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex (By similarity). This leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (By similarity). Activated by CARD9 downstream of C-type lectin receptors; CARD9-mediated signals are essential for antifungal immunity (PubMed:22265677). Activated by CARD11 downstream of T-cell receptor (TCR) and B-cell receptor (BCR) (By similarity). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK (By similarity).|||Proteolytically cleaved by MALT1; required for T-cell activation.|||Ubiquitinated via both 'Lys-63'-linked and linear ('Met-1'-linked) polyubiquitin chains in response to T-cell receptor (TCR) activation. Ubiquitination is recognized by IKBKG/NEMO, the regulatory subunit of I-kappa-B kinase (IKK), and is required for TCR-induced NF-kappa-B activation. Linear ubiquitination at Lys-17, Lys-31 and Lys-63 is mediated by RNF31/HOIP; linear ubiquitination is recognized with much higher affinity than 'Lys-63'-linked ubiquitin by IKBKG/NEMO. CARD11 is required for linear ubiquitination by HOIP by promoting the targeting of BCL10 to RNF31/HOIP. http://togogenome.org/gene/10090:Or4k6 ^@ http://purl.uniprot.org/uniprot/F8VQB9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Msx2 ^@ http://purl.uniprot.org/uniprot/Q03358|||http://purl.uniprot.org/uniprot/Q3UZH5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator in bone development. Represses the ALPL promoter activity and antagonizes the stimulatory effect of DLX5 on ALPL expression during osteoblast differentiation. Probable morphogenetic role. May play a role in limb-pattern formation. In osteoblasts, suppresses transcription driven by the osteocalcin FGF response element (OCFRE). Binds to the homeodomain-response element of the ALPL promoter.|||Belongs to the Msh homeobox family.|||Expressed in mesenchymal tissue in the developing spinal cord and limbs.|||Interacts with MINT. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80) (By similarity).|||Nucleus|||Up-regulated by BMP2. http://togogenome.org/gene/10090:Ivd ^@ http://purl.uniprot.org/uniprot/Q9JHI5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-76 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the acyl-CoA dehydrogenase family.|||Catalyzes the conversion of isovaleryl-CoA/3-methylbutanoyl-CoA to 3-methylbut-2-enoyl-CoA as an intermediate step in the leucine (Leu) catabolic pathway. To a lesser extent, is also able to catalyze the oxidation of other saturated short-chain acyl-CoA thioesters as pentanoyl-CoA, hexenoyl-CoA and butenoyl-CoA.|||Homotetramer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Pitx1 ^@ http://purl.uniprot.org/uniprot/P70314|||http://purl.uniprot.org/uniprot/Q3UQH0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Expressed in primordial Rathke pouch, oral epithelium, first branchial arch, duodenum, and hindlimb.|||Expressed throughout pituitary development. Not found in 8 dpc embryos but seen in embryos at 8.5 dpc in the region of the first branchial arch and ventral portion of the caudal-most region of the embryo. At 9.5 dpc observed in the hindlimb buds, maxillary and mandibular components of the first branchial arch and Rathke pouch and the pattern of expression continues through 10.5 dpc at 11.5 dpc also found in ventral mesenchyme covering the abdominal cavity and in the nasal epithelium. At 17.5 dpc expressed in derivatives of the first branchial arch, including tongue and mandible as well as duodenum, salivary glands, nasal epithelium and condensing cartilage in the hindlimbs.|||Interacts with POU1F1.|||Nucleus|||Sequence-specific transcription factor that binds gene promoters and activates their transcription. May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb. Can independently activate and synergize with PIT-1 on pituitary-specific target gene promoters, thus may subserve functions in generating both precursor and specific cell phenotypes in the anterior pituitary gland and in several other organs. Can activate pituitary transcription of the proopiomelanocortin gene. http://togogenome.org/gene/10090:Shc1 ^@ http://purl.uniprot.org/uniprot/P98083 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||In response to a variety of growth factors, isoform p47Shc and isoform p52 bind to phosphorylated receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif. Isoform p47Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation.|||Interacts with CPNE3; this interaction may mediate the binding of CPNE3 with ERBB2 (By similarity). Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain. Once activated, binds to GRB2. Interacts with tyrosine-phosphorylated DDR2 and CD3T. Interacts with the N-terminal region of APS. Interacts with GRB7 and KIT (By similarity). Interacts with PTK2/FAK1 (By similarity). Interacts with phosphorylated LRP1 and IRS4. Interacts with FLT4 (tyrosine-phosphorylated) (By similarity). Interacts with PDGFRB (tyrosine-phosphorylated). Interacts with ERBB4 (By similarity). Interacts with TEK/TIE2 (tyrosine-phosphorylated) (By similarity). Interacts with ALK, GAB2, TRIM31, INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with PTPN6/SHP (tyrosine phosphorylated). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with EPHB1 and GRB2; activates the MAPK/ERK cascade to regulate cell migration. Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. Interacts with CEACAM1; this interaction is CEACAM1-phosphorylation-dependent and mediates interaction with EGFR or INSR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity) (PubMed:15467833). Interacts (via PID domain) with PEAK1 (when phosphorylated at 'Tyr-1177') (By similarity). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity).|||Mitochondrion|||Mitochondrion matrix|||Phosphorylated in response to FLT4 signaling (By similarity). Tyrosine phosphorylated by ligand-activated PDGFRB (By similarity). May be tyrosine phosphorylated by activated PTK2/FAK1 (By similarity). Tyrosine phosphorylated by TEK/TIE2 (By similarity). Tyrosine phosphorylated by activated PTK2B/PYK2 (By similarity). Dephosphorylation by PTPN2 may regulate interaction with GRB2 (By similarity). Phosphorylated by activated epidermal growth factor receptor. Phosphorylated in response to KIT signaling. Isoform p47Shc and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-rich domain. Isoform p66Shc is phosphorylated on Ser-36 by PRKCB upon treatment with insulin, hydrogen peroxide or irradiation with ultraviolet light. FLT3 signaling promotes tyrosine phosphorylation of isoform p47Shc and isoform p52Shc. Also tyrosine phosphorylated by ligand-activated ALK.|||Produced by alternative initiation at Met-46 of isoform p52.|||Produced by alternative splicing.|||Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis (By similarity). Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p47Shc and isoform p52Shc, once phosphorylated, couple activated receptor kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p47Shc and isoform p52 may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span.|||Widely expressed. Expressed in neural stem cells but absent in mature neurons.|||focal adhesion http://togogenome.org/gene/10090:Elmod3 ^@ http://purl.uniprot.org/uniprot/Q91YP6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a GTPase-activating protein (GAP) for ARL2 with low specific activity.|||Both isoform 1 and isoform 2 are expressed postnatally in the inner ear. Expression increases from P0 to P30 in both cochlear and vestibular tissues; at all time points, isoform 2 is expressed at several-fold higher levels than isoform 1. At P14, in the organ of Corti, detected along the length of stereocilia of hair cells, particularly in the upper half. Also observed in the microvilli on the apical surface of the hair cells. More abundant in the stereocilia of inner hair cells than in those of outer hair cells (at protein level). In the vestibular sensory epithelium, localizes within the hair cell and supporting cell bodies in the saccule and utricule. Not detected in vestibular hair bundles (at protein level).|||Both isoform 1 and isoform 2 are widely expressed.|||cytoskeleton|||kinocilium|||stereocilium http://togogenome.org/gene/10090:Pdcd6ip ^@ http://purl.uniprot.org/uniprot/Q9WU78 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Deficient mice are viable and have a normal lifespan, although they are smaller in size. Mutant mice develop progressive and severe bilateral hydrocephalus (PubMed:27336173).|||Does not interact with ALG-2.|||May be phosphorylated on tyrosine residues by activated PDGFRB.|||Melanosome|||Midbody ring|||Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (By similarity). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (PubMed:27336173).|||Self-associates (By similarity). Interacts with SH3KBP1 (By similarity). Interacts with PDCD6 in a calcium-dependent manner (By similarity). Interacts with TSG101 in a calcium-dependent manner; PDCD6IP homooligomerization may be required for TSG101-binding (By similarity). Interacts with SGSM3 (By similarity). Directly interacts with CHMP4A, CHMP4B and CHMP4C (By similarity). Directly interacts with CEP55 in a 1:2 stoechiometry; this interaction is required for PDCD6IP targeting to the midbody (By similarity). May interact with PDGFRB (By similarity). Interacts with SH3GL1 and SH3GL2/endophilin-1 (By similarity). Forms a complex with SDCBP and SDC2 (PubMed:22660413). Found in a complex with F-actin, TJP1/ZO-1 and PARD3 (PubMed:27336173). Interacts with CD2AP (By similarity). Interacts with ARRDC1 (By similarity).|||Ubiquitously expressed (PubMed:27336173). High expression in choroid plexus and low expression in cerebral cortex (at protein level) (PubMed:27336173).|||centrosome|||cytosol|||extracellular exosome|||tight junction http://togogenome.org/gene/10090:Adss ^@ http://purl.uniprot.org/uniprot/B9EIE9|||http://purl.uniprot.org/uniprot/P46664 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylosuccinate synthetase family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Homodimer.|||Inhibited competitively by AMP and IMP and non-competitively by fructose 1,6-bisphosphate.|||Mitochondrion|||Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.|||Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.|||Plays an important role in the de novo pathway of purine nucleotide biosynthesis. http://togogenome.org/gene/10090:Slc26a8 ^@ http://purl.uniprot.org/uniprot/Q8R0C3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiporter that mediates the exchange of sulfate and oxalate against chloride ions across a membrane. Stimulates anion transport activity of CFTR (By similarity). May cooperate with CFTR in the regulation of chloride and bicarbonate ions fluxes required for activation of the ADCY10/PKA pathway during sperm motility and sperm capacitation (PubMed:22121115). May play a role in sperm tail differentiation and motility and hence male fertility (PubMed:17517695).|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Expressed in testis and epididymis. Located at the end of the midpiece of the flagella, known as the annulus, in spermatozoa.|||Homozygous knockout mice lacking Tat1 are viable and indistinguishable from their wild-type littermates in survival rate, general appearance, and gross behavior (i.e. size, weight, fur, and activity) (PubMed:17517695). However, over a period of two months, males becames infertile despite normal sexual behavior (PubMed:17517695). Sperm lacks motility and displayed a capacitation defect (PubMed:17517695).|||Interacts with RACGAP1. Interacts with CFTR; stimulates anion transport activity of CFTR.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Timm21 ^@ http://purl.uniprot.org/uniprot/Q8CCM6 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TIM21 family.|||Component of the TIM23 complex. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14. Interacts with COA3 and MT-CO1/COX1.|||Mitochondrion membrane|||Participates in the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Also required for assembly of mitochondrial respiratory chain complex I and complex IV as component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex. Probably shuttles between the presequence translocase and respiratory-chain assembly intermediates in a process that promotes incorporation of early nuclear-encoded subunits into these complexes.|||Probable cloning artifact. http://togogenome.org/gene/10090:Nagk ^@ http://purl.uniprot.org/uniprot/Q3U2G9|||http://purl.uniprot.org/uniprot/Q9D997|||http://purl.uniprot.org/uniprot/Q9QZ08 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic-type N-acetylglucosamine kinase family.|||Converts endogenous N-acetylglucosamine (GlcNAc), a major component of complex carbohydrates, from lysosomal degradation or nutritional sources into GlcNAc 6-phosphate (PubMed:10824116). Also has N-acetylmannosamine (ManNAc) kinase activity (PubMed:10824116). Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway (PubMed:22692205). Also involved in innate immunity by promoting detection of bacterial peptidoglycan by NOD2: acts by catalyzing phosphorylation of muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, to generate 6-O-phospho-muramyl dipeptide, which acts as a direct ligand for NOD2 (PubMed:36002575).|||Homodimer.|||No visible phenotype in absence of infection (PubMed:36002575). Macrophages are completely deficient in muramyl dipeptide (MDP) sensing (PubMed:36002575).|||Ubiquitous. http://togogenome.org/gene/10090:Prl8a1 ^@ http://purl.uniprot.org/uniprot/Q9DAV8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Or8k39 ^@ http://purl.uniprot.org/uniprot/A0A1L1SRK6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cpne9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J1|||http://purl.uniprot.org/uniprot/Q1RLL3|||http://purl.uniprot.org/uniprot/Q8BRJ6 ^@ Function|||Similarity ^@ Belongs to the copine family.|||Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes. Plays a role in dendrite formation by melanocytes. http://togogenome.org/gene/10090:Gda ^@ http://purl.uniprot.org/uniprot/D3YU09|||http://purl.uniprot.org/uniprot/Q548F2|||http://purl.uniprot.org/uniprot/Q9R111 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the metallo-dependent hydrolases superfamily. ATZ/TRZ family.|||Binds 1 zinc ion per subunit.|||Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.|||Homodimer. http://togogenome.org/gene/10090:Gpr82 ^@ http://purl.uniprot.org/uniprot/Q8BZR0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Exosc7 ^@ http://purl.uniprot.org/uniprot/Q9D0M0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase PH family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts with EXOSC1 (By similarity). Interacts with ZC3HAV1 (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Kctd13 ^@ http://purl.uniprot.org/uniprot/Q8BGV7 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BACURD family.|||By TNF-alpha.|||Down-regulation of Kctd13 was initially reported to cause macrocephaly due to increased proliferation (PubMed:22596160). However, it was later shown that deletion of Kctd13 does not cause any change in brain size, embryonic cell proliferation, neurogenesis, or cortical layering/migration (PubMed:29088697). Experimental conditions used may explain discrepancies. A possible explanation being that shRNAs used in the first study, may have affected off-targets.|||Homotetramer; forms a two-fold symmetric tetramer in solution. Interacts with CUL3; interaction is direct and forms a 5:5 heterodecamer. Component of the BCR(KCTD13) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD13/BACURD1 and RBX1. Interacts with RHOA; with a preference for RhoA-GDP. Interacts with POLD2 and PCNA. Interacts with SPRTN.|||Nucleus|||Reduced synaptic transmission in area CA1 of the hippocampus caused by increased levels of RHOA. Brain size or neural progenitor cell proliferation are not affected.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for synaptic transmission (PubMed:29088697). The BCR(KCTD13) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and promoting synaptic transmission (PubMed:29088697). http://togogenome.org/gene/10090:Cavin4 ^@ http://purl.uniprot.org/uniprot/A2AMM0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in cardiac and skeletal muscle (at protein level). Weaker expression in aorta and lung. In heart, expressed in cardiomyocytes and vascular smooth muscle cells but not in other surrounding cells including vascular endothelial cells.|||Belongs to the CAVIN family.|||Cell membrane|||Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4. Interacts with CAVIN1 (PubMed:19546242). Interacts with CAVIN2; this augments the transactivation of NPPA. Interacts with CAV3, ADRA1A, ADRA1B, MAPK1 and MAPK3 (By similarity).|||Cytoplasm|||Expression increases during development from embryo to adult.|||Mice exhibit normal caveolar morphology and cardiac function under physiological conditions, whereas upon alpha-1 adrenergic receptor stimulation, show attenuation of cardiac hypertrophy accompanied by suppressed MAPK1/2 activation.|||Modulates the morphology of formed caveolae in cardiomyocytes, but is not required for caveolar formation. Facilitates the recruitment of MAPK1/3 to caveolae within cardiomyocytes and regulates alpha-1 adrenergic receptor-induced hypertrophic responses in cardiomyocytes through MAPK1/3 activation (PubMed:24567387). Contributes to proper membrane localization and stabilization of caveolin-3 (CAV3) in cardiomyocytes (PubMed:26497963). Induces RHOA activation and activates NPPA transcription and myofibrillar organization through the Rho/ROCK signaling pathway (PubMed:18332105).|||The coiled coil domain (residues 44-77) is essential for membrane-targeting in cardiomyocytes.|||Up-regulated in response to cardiac hypertrophy.|||caveola|||cytosol|||sarcolemma|||sarcomere http://togogenome.org/gene/10090:Fhod3 ^@ http://purl.uniprot.org/uniprot/Q76LL6 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the formin homology family.|||Expressed in the heart, including left ventricle, kidney, brain and skeletal muscle, including soleus and tibialis anterior (at protein level).|||Interacts with nestin/NES-based interfilament (IF). Interacts with SQSTM1.|||Major form in heart.|||Major form in kidney and brain.|||May play a role in actin filament polymerization in cardiomyocytes (By similarity). Actin-organizing protein that may cause stress fiber formation together with cell elongation.|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).|||Z line|||cytoskeleton http://togogenome.org/gene/10090:Tmem223 ^@ http://purl.uniprot.org/uniprot/Q9CQE2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial ribosome.|||Belongs to the TMEM223 family.|||Mitochondrial ribosome-associated protein involved in the first steps of cytochrome c oxidase complex (complex IV) biogenesis. Stimulates the translation of MT-CO1 mRNA and is a constituent of early MT-CO1 assembly intermediates.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Flt3 ^@ http://purl.uniprot.org/uniprot/Q00342|||http://purl.uniprot.org/uniprot/Q3UEW6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on several tyrosine residues in response to FLT3LG binding. FLT3LG binding also increases phosphorylation of mutant kinases that are constitutively activated. Dephosphorylated by PTPRJ/DEP-1, PTPN1, PTPN6/SHP-1, and to a lesser degree by PTPN12. Dephosphorylation is important for export from the endoplasmic reticulum and location at the cell membrane (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Endoplasmic reticulum lumen|||Hematopoietic stem and progenitor cell-enriched populations. Found in brain, placenta and testis.|||Membrane|||Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation. Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2 (By similarity). Interacts with RNF115 and RNF126.|||N-glycosylated, contains complex N-glycans with sialic acid.|||No visible phenotype. Mice are born at the expected Mendelian rate, develop normally and are fertile. They show normal blood cell counts, excepting reduced levels of primitive B-cell progenitors. Mice lacking both Flt3 and Kit show a reduction in both lymphoid and myeloid cell lineages. They appear normal, but are born at a lower frequency than expected and exhibit severely reduced viability after 3 weeks, none surviving more than six weeks.|||Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.|||Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.|||The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated further by FLT3LG binding (By similarity).|||Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. http://togogenome.org/gene/10090:Or4m1 ^@ http://purl.uniprot.org/uniprot/Q8VFT4 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Compared to wild-type mice, mutant mice fed on a regular diet show a remarkable decrease in body weight, food intake, fat mass and plasma lipids (PubMed:31230984). Blunted response to Asprosin, including attenuated cAMP levels and hepatic glucose production, as well as improved insulin sensitivity (PubMed:31230984). Mutant mice show significantly reduced food intake in overnight-fasted mice compared with wild-type mice (PubMed:32337066). Male mice display decreased fertility caused by impaired sperm motility (PubMed:31798959).|||Highly expressed in liver but not in adipose tissue (PubMed:31230984). Also expressed at high level in testis (PubMed:31798959).|||Olfactory receptor that acts as a receptor of Asprosin hormone at the surface of hepatocytes to promote hepatocyte glucose release (PubMed:31230984). Also binds Asprosin in the arcuate nucleus of the hypothalamus, thereby stimulating appetite by promoting orexigenic AgRP neuronal activity (PubMed:32337066). In testis, Asprosin-binding promotes sperm progressive motility and enhances male fertility (PubMed:31798959). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase, resulting in an elevation of intracellular cAMP (PubMed:31230984).|||The mouse olfactory receptor 4M1 (Q8VFT4) is not the one to one ortholog of human OR4M1 (Q8NGD0). http://togogenome.org/gene/10090:Or11g26 ^@ http://purl.uniprot.org/uniprot/A2RTP5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mtmr4 ^@ http://purl.uniprot.org/uniprot/Q91XS1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr residues and low molecular weight phosphatase substrate para-nitrophenylphosphate. Phosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity).|||Membrane http://togogenome.org/gene/10090:Sigirr ^@ http://purl.uniprot.org/uniprot/Q3UKS3|||http://purl.uniprot.org/uniprot/Q9JLZ8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP (By similarity).|||Belongs to the interleukin-1 receptor family.|||Down-regulated by LPS. Down-regulated during inflammation by inhibition of an SP1-mediated pathway.|||Expressed at high levels in kidney, and at moderate levels in colon, small intestine, lung, spleen and liver. Not expressed in brain and muscle. Expressed at high levels in epithelial cells, at moderate levels in splenocytes, and at low or undetectable levels in fibroblasts or endothelial cells. Expressed in mucosal and dendritic cells.|||Interacts with IL1R1, IRAK1, TLR4, TLR5, TLR9 and TRAF6. Upon IL-1 stimulation found in a complex at least composed of IL1R1, SIGIRR, MYD88, IRAK1 and TRAF6. Upon stimulation with LPC found in a complex at least composed of TLR4, SIG1IR, MYD88, IRAK1 and TRAF6. Interacts with PALM3 (By similarity).|||Membrane http://togogenome.org/gene/10090:Ube2t ^@ http://purl.uniprot.org/uniprot/Q9CQ37 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair: acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCL and FANCI. May contribute to ubiquitination and degradation of BRCA1. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination.|||Auto-ubiquitinated. Effects of auto-monoubiquitination at Lys-91 and Lys-181 are unclear.|||Belongs to the ubiquitin-conjugating enzyme family.|||Interacts with FANCL and BRCA1.|||Nucleus http://togogenome.org/gene/10090:Gm21396 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Spdya ^@ http://purl.uniprot.org/uniprot/B2RWC8|||http://purl.uniprot.org/uniprot/Q5IBH7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Speedy/Ringo family.|||Expressed at a high level in testis. Also expressed in the adult ovary and in immature oocytes.|||Interacts with CDK1, CDK2 and CDKN1B/KIP1 (PubMed:15611625). Identified in a complex with CDK2 and CDKN1B/KIP1, where it interacts primarily with CDK2 (By similarity).|||Nucleus|||Regulates the G1/S phase transition of the cell cycle by binding and activating CDK1 and CDK2 (PubMed:15611625). Contributes to CDK2 activation without promoting CDK2 phosphorylation, by inducing a conformation change of the CDK2 T-loop that obstructs the substrate-binding cleft prior to kinase activation. Interferes with CDKN1B-mediated inhibition of CDK2. Mediates cell survival during the DNA damage process through activation of CDK2 (By similarity).|||The C-terminus is required for CDK2-activation, but not CDK2-binding. http://togogenome.org/gene/10090:Usf1 ^@ http://purl.uniprot.org/uniprot/Q61069 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer (USF1/USF2).|||Nucleus|||Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. http://togogenome.org/gene/10090:Tnfsf14 ^@ http://purl.uniprot.org/uniprot/A0A0U5JAA8|||http://purl.uniprot.org/uniprot/Q9QYH9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF3/LTBR. Binding to the decoy receptor TNFRSF6B modulates its effects. Activates NFKB and stimulates the proliferation of T-cells. Acts as a ligand for TNFRSF14/HVEM. Upon binding to TNFRSF14/HVEM, delivers costimulatory signals to T cells, leading to T cell proliferation and IFNG production (By similarity).|||Homotrimer. Interacts with TNFRSF14.|||Secreted|||The soluble form derives from the membrane form by proteolytic processing. http://togogenome.org/gene/10090:Or5w16 ^@ http://purl.uniprot.org/uniprot/Q7TR39 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Smoc2 ^@ http://purl.uniprot.org/uniprot/A0A3B2WCK7|||http://purl.uniprot.org/uniprot/Q8CD91 ^@ Caution|||Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16.5 dpc, present in rib cartilage, choroid plexus epithelium and associated blood vessels, and developing oral and tooth germ epithelia (at protein level).|||Binds various proteins from the extracellular matrix.|||Can stimulate endothelial cell proliferation, migration, as well as angiogenesis (By similarity). Promotes matrix assembly and cell adhesiveness.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Strongly expressed in ovary, followed by heart, muscle, spleen, brain, thymus, lung, liver, kidney, spleen, testis, ovary and skeletal muscle.|||basement membrane http://togogenome.org/gene/10090:Gm6176 ^@ http://purl.uniprot.org/uniprot/J3QK59 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Srek1 ^@ http://purl.uniprot.org/uniprot/Q8BZX4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Homodimer. Binds SFRS1, SFRS2, SFRS3 and SFRS6. Interacts with the spliceosome. Interacts with SREK1IP1 (By similarity).|||Nucleus|||Participates in the regulation of alternative splicing by modulating the activity of other splice facors. Inhibits the splicing activity of SFRS1, SFRS2 and SFRS6. Augments the splicing activity of SFRS3 (By similarity). http://togogenome.org/gene/10090:Gja3 ^@ http://purl.uniprot.org/uniprot/A0A654ICY8|||http://purl.uniprot.org/uniprot/Q64448 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins.|||A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels. Forms heteromeric channels with GJA8.|||Belongs to the connexin family. Alpha-type (group II) subfamily.|||Cell membrane|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||Structural component of lens fiber gap junctions. Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane. Small molecules and ions diffuse from one cell to a neighboring cell via the central pore.|||gap junction http://togogenome.org/gene/10090:Kpna4 ^@ http://purl.uniprot.org/uniprot/O35343|||http://purl.uniprot.org/uniprot/Q4FJX1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the importin alpha family.|||Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.|||Cytoplasm|||Detected more or less in all tissues examined (Ehrlich ascites tumor cells, testis, kidney, spleen, liver, heart, lung, thymus, skeletal muscle, cerebellum and brain (without cerebellum)). Multiple-sized transcripts were highly expressed, especially in testis.|||Forms a complex with importin subunit beta-1. Interacts with SNAI1 (By similarity). Interacts with TALDO1 isoform 1 (PubMed:27703206).|||Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.|||Functions in nuclear protein import.|||Nucleus|||The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity).|||The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity). http://togogenome.org/gene/10090:Cpn1 ^@ http://purl.uniprot.org/uniprot/Q9JJN5 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Mainly expressed in liver. Also detected in lung, stomach, intestine, spleen and kidney.|||Protects the body from potent vasoactive and inflammatory peptides containing C-terminal Arg or Lys (such as kinins or anaphylatoxins) which are released into the circulation.|||Tetramer of two catalytic chains and two glycosylated inactive chains.|||extracellular space http://togogenome.org/gene/10090:Ranbp6 ^@ http://purl.uniprot.org/uniprot/A3KMD2|||http://purl.uniprot.org/uniprot/Q8BIV3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the importin beta family.|||Cytoplasm|||May function in nuclear protein import as nuclear transport receptor.|||Nucleus http://togogenome.org/gene/10090:Ppp1r14b ^@ http://purl.uniprot.org/uniprot/Q62084 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PP1 inhibitor family.|||Cytoplasm|||Inhibitor of PPP1CA. Has over 50-fold higher inhibitory activity when phosphorylated.|||Phosphorylated primarily on Thr-57 by PKC (in vitro). An unknown Ser is also phosphorylated by PKC (in vitro).|||Ubiquitous. Highly expressed in testis. Detected at low levels in the other tissues tested. Highly expressed in cardiac muscle, bladder and aorta (at protein level). http://togogenome.org/gene/10090:Gm20883 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1|||http://purl.uniprot.org/uniprot/A0A087WSR0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Itgad ^@ http://purl.uniprot.org/uniprot/E9PXZ7|||http://purl.uniprot.org/uniprot/H3BKX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the integrin alpha chain family.|||Membrane http://togogenome.org/gene/10090:Niban1 ^@ http://purl.uniprot.org/uniprot/Q3UW53 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ 'Niban' means 'second' in Japanese.|||Belongs to the Niban family.|||By endoplasmic reticulum stress-inducing agents such as tunicamycin and thapsigargin in liver, kidney and cerebrum.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Intron retention.|||Membrane|||No obvious phenotypic abnormalities but mice show increased phosphorylation of Eif2a and decreased phosphorylation of Eif4ebp1 and Rps6kb1.|||Regulates phosphorylation of a number of proteins involved in translation regulation including EIF2A, EIF4EBP1 and RPS6KB1. May be involved in the endoplasmic reticulum stress response. http://togogenome.org/gene/10090:Mrgprb1 ^@ http://purl.uniprot.org/uniprot/Q3UG61 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Membrane|||Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Mef2a ^@ http://purl.uniprot.org/uniprot/Q60929 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation on Lys-401 activates transcriptional activity. Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation. Hyperacetylation by p300 leads to enhanced cardiac myocyte growth and heart failure (By similarity).|||Belongs to the MEF2 family.|||Binds DNA as a homo- or heterodimer. Dimerizes with MEF2D. Interacts with HDAC7. Interacts with PIAS1; the interaction enhances sumoylation. Interacts with HDAC4, HDAC9 and SLC2A4RG. Interacts (via the N-terminal) with MAPK7; the interaction results in the phosphorylation and transcriptional activity of MEF2A (By similarity).|||Constitutive phosphorylation on Ser-406 promotes Lys-401 sumoylation thus preventing acetylation at this site. Dephosphorylation on Ser-406 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation. Phosphorylation on Thr-312 and Thr-319 are the main sites involved in p38 MAPK signaling and activate transcription. Phosphorylated on these sites by MAPK14/p38alpha and MAPK11/p38beta, but not by MAPK13/p38delta nor by MAPK12/p38gamma. Phosphorylation on Ser-408 by CDK5 induced by neurotoxicity inhibits MEF2A transcriptional activation leading to apoptosis of cortical neurons. Phosphorylation on Thr-312, Thr-319 and Ser-355 can be induced by EGF (By similarity). Isoform 3 is phosphorylated on Ser-98 and Thr-108.|||In the developing cerebellum, increasing levels after birth. The majority of this increase occurs around postnataL day 9 reaching a peak at postnatal day 15-18 which is maintained in adults.|||Nucleus|||Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 3 and caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity).|||Sumoylation on Lys-401 is enhanced by PIAS1 and represses transcriptional activity. Phosphorylation on Ser-406 is required for sumoylation. Has no effect on nuclear location nor on DNA binding. Sumoylated with SUMO1 and, to a lesser extent with SUMO2 and SUMO3. PIASx facilitates sumoylation in postsynaptic dendrites in the cerebellar cortex and promotes their morphogenesis (By similarity).|||The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.|||Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter (By similarity).|||Widely expressed though mainly restricted to skeletal and cardiac muscle, brain, neurons and lymphocytes. Differentially expressed depending on if isoforms contain the beta domain or not, with the total expression of the beta domain-lacking isoforms vastly exceding that of the beta domain-containing isoforms. Isoforms containing the beta domain are expressed primarily in skeletal and cardiac muscle and in brain. Also present in lung and testis. Splicing to include the beta domain is induced in differentiating myocytes. Isoforms lacking the beta domain are expressed less abundantly in skeletal muscle, brain and lymphocytes, and are uniquely found in ovary, liver, spleen and kidney. In embryos, the beta domain-containing and beta domain-lacking isoforms are equally expressed. Also expressed cerebellar granule neurons and other regions of the CNS. Highest levels in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum. http://togogenome.org/gene/10090:Exosc1 ^@ http://purl.uniprot.org/uniprot/Q9DAA6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CSL4 family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts with EXOSC5, EXOSC7 and EXOSC10 (By similarity). Interacts with DDX60 (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC1 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC6 and EXOSC8 (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Pakap ^@ http://purl.uniprot.org/uniprot/O54931 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Binds to regulatory subunit (RII) of protein kinase A (PubMed:9497389). May be involved in establishing polarity in signaling systems or in integrating PKA-RII isoforms with downstream effectors to capture, amplify and focus diffuse, trans-cellular signals carried by cAMP (PubMed:9497389). Binds tp and modulates the structure of the actin cytoskeleton (PubMed:9497389).|||Highly expressed in lung and weakly in thymus and cerebellum (PubMed:9497389). Little or no expression in liver, heart and cerebral cortex (PubMed:9497389). All isoforms are expressed in lung, but KL2A and KL2B isoforms are the principal isoforms in cerebellum (PubMed:9497389).|||Produced by alternative initiation at Met-321 of isoform KL1A.|||Produced by alternative initiation at Met-321 of isoform KL2A.|||Produced by alternative splicing.|||The RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer. http://togogenome.org/gene/10090:Map3k20 ^@ http://purl.uniprot.org/uniprot/Q9ESL4 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation by PKN1, followed by autophosphorylation on Thr-161 and Ser-165 (By similarity). Autophosphorylation in response to ribotoxic stress promotes dissociation from colliding ribosomes and activation (By similarity).|||Activated in response to stress, such as ribosomal stress, osmotic shock and ionizing radiation. Activated by phosphorylation by PKN1, followed by autophosphorylation on Thr-161 and Ser-165.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cytoplasm|||Homodimer (PubMed:11042189). Interacts with ZNF33A (By similarity). Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, MAP3K20 and MAP2K3 (By similarity). Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and MAP3K20 (By similarity). Interacts with EIF2AK4/GCN2; promoting EIF2AK4/GCN2 kinase activity (By similarity).|||Interacts with isoform ZAKalpha.|||Interacts with isoform ZAKbeta.|||Isoform that lacks the C-terminal region that mediates ribosome-binding: does not act as a sensor of ribosome collisions in response to ribotoxic stress. May act as an antagonist of isoform ZAKalpha: interacts with isoform ZAKalpha, leading to decrease the expression of isoform ZAKalpha.|||Key component of the stress-activated protein kinase signaling cascade in response to ribotoxic stress or UV-B irradiation (PubMed:32289254). Acts as the proximal sensor of ribosome collisions during the ribotoxic stress response (RSR) (PubMed:32289254). Directly binds to the ribosome by inserting its flexible C-terminus into the ribosomal intersubunit space, thereby acting as a sentinel for colliding ribosomes (By similarity). Upon ribosome collisions, activates either the stress-activated protein kinase signal transduction cascade or the integrated stress response (ISR), leading to programmed cell death or cell survival, respectively (By similarity). Dangerous levels of ribosome collisions trigger the autophosphorylation and activation of MAP3K20, which dissociates from colliding ribosomes and phosphorylates MAP kinase kinases, leading to activation of the JNK and MAP kinase p38 pathways that promote programmed cell death (By similarity). Less dangerous levels of ribosome collisions trigger the integrated stress response (ISR): MAP3K20 activates EIF2AK4/GCN2 independently of its protein-kinase activity, promoting EIF2AK4/GCN2-mediated phosphorylation of EIF2S1/eIF-2-alpha (By similarity). Also acts as a histone kinase by phosphorylating histone H3 at 'Ser-28' (H3S28ph) (By similarity).|||Knockout results in fully penetrant lethality at 9.5 dpc due to severe cardiac edema and growth retardation (PubMed:26755636). Embryos show polydactyly of the feet (PubMed:26755636). Defects in stress-activated protein kinase signaling cascade in response to ribotoxic stress, leading to impaired activation of the JNK and MAP kinase p38 pathways (PubMed:27598200).|||Mainly expressed in heart and developing limbs.|||Nucleus|||Recognizes stalled ribosomes via two separate and partially redundant sensor domains: the C-terminal domain (CTD) that binds the 18S ribosomal RNA (18S rRNA) and the sensing domain (S).|||Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation (PubMed:11042189, PubMed:27598200). Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JNK (MAPK8/JNK1, MAPK9/JNK2 and/or MAPK10/JNK3) and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11042189). Activates JNK through phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7, and MAP kinase p38 gamma (MAPK12) via phosphorylation of MAP2K3/MKK3 and MAP2K6/MKK6 (PubMed:11042189). Involved in stress associated with adrenergic stimulation: contributes to cardiac decompensation during periods of acute cardiac stress (By similarity). May be involved in regulation of S and G2 cell cycle checkpoint by mediating phosphorylation of CHEK2 (By similarity). http://togogenome.org/gene/10090:Slc26a11 ^@ http://purl.uniprot.org/uniprot/Q80ZD3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in the cerebellum, with a predominant expression in Purkinje cells (at protein level).|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Cell membrane|||Conditional knockout from Purkinje cells (PCs) induces a negative shift in the reversal potential of chloride as reflected in the GABAA-receptor evoked currents, indicating a decrease in intracellular chloride concentration. Both in vitro and in vivo, PCs show a significantly increased action potential firing frequency of simple spikes. At the behavioral level, mice show deficits in locomotor activity.|||Lysosome membrane|||Predominantly expressed in the brain with lower levels in the kidney.|||Predominantly expressed in the kidney and brain (PubMed:21716257). In the kidney localizes in collecting duct intercalated cells (at protein level) (PubMed:21716257).|||Sodium-independent anion exchanger mediating bicarbonate, chloride, sulfate and oxalate transport (By similarity). Exhibits sodium-independent sulfate anion transporter activity that may cooperate with SLC26A2 to mediate DIDS-sensitive sulfate uptake into high endothelial venules endothelial cells (HEVEC) (By similarity). In the kidney, mediates chloride-bicarbonate exchange, facilitating V-ATPase-mediated acid secretion (PubMed:21716257). May function as a chloride channel, playing an important role in moderating chloride homeostasis and neuronal activity in the cerebellum (PubMed:23733100, PubMed:27390771). http://togogenome.org/gene/10090:Cstb ^@ http://purl.uniprot.org/uniprot/Q62426 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Cytoplasm|||This is an intracellular thiol proteinase inhibitor.|||Widely expressed. Highest expression in heart, liver and kidney. Lower levels in brain, lung and skeletal muscle. Lowest levels in spleen and testis. http://togogenome.org/gene/10090:Aldh3b2 ^@ http://purl.uniprot.org/uniprot/E9Q3E1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Expressed in testis, white adipose tissue, lung, small intestine, kidney, spleen and liver.|||Geranylgeranylation is important for localization to lipid droplets and enzyme activity.|||Lipid droplet|||Oxidizes medium and long chain aldehydes into non-toxic fatty acids. http://togogenome.org/gene/10090:Tnfrsf18 ^@ http://purl.uniprot.org/uniprot/O35714 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6 (By similarity). Binds through its C-terminus to SIVA1/SIVA.|||Cell membrane|||Preferentially expressed in activated T lymphocytes.|||Receptor for TNFSF18. Seems to be involved in interactions between activated T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death. Mediated NF-kappa-B activation via the TRAF2/NIK pathway (By similarity).|||Secreted|||Up-regulated in peripherical mononuclear cells after antigen stimulation/lymphocyte activation. http://togogenome.org/gene/10090:Nipal3 ^@ http://purl.uniprot.org/uniprot/A2A987|||http://purl.uniprot.org/uniprot/Q8BGN5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NIPA family.|||Membrane http://togogenome.org/gene/10090:Nkd2 ^@ http://purl.uniprot.org/uniprot/Q8VE28 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKD family.|||Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity. Required for processing of TGFA and for targeting of TGFA to the basolateral membrane of polarized epithelial cells (By similarity).|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Expressed in the cecum, colon, esophagus, ileum, jejunum, skin and stomach.|||Expressed in the forelimb buds, the branchial arches, the caudal presomitic mesoderm (PSM) and at the anterior and posterior of each somite boundary at 9.5 days postcoitum (dpc). Also expressed in the tailbud.|||Interacts with RNF25, TGFA (via cytoplasmic domain), and PPP2R3A (By similarity). Interacts with DVL1, DVL2 and DVL3.|||The N-terminal domain comprising the first 224 amino acid residues is mostly unstructured.|||Ubiquitinated, leading to rapid proteasomal degradation. Interaction with TGFA interferes with RNF25 binding and protects against ubiquitination mediated by RNF25 (By similarity). http://togogenome.org/gene/10090:Gpr85 ^@ http://purl.uniprot.org/uniprot/P60894|||http://purl.uniprot.org/uniprot/Q6ZWR2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Endoplasmic reticulum|||Exclusively expressed in brain.|||Interacts with DLG4 and DLG3.|||Membrane|||Orphan receptor. http://togogenome.org/gene/10090:Lmbr1l ^@ http://purl.uniprot.org/uniprot/Q9D1E5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LIMR family.|||Cell membrane|||Dimer (By similarity). Can also form higher oligomers (By similarity). Interacts with LCN1; this interaction mediates the endocytosis of LCN1 (By similarity). Interacts with UBAC2, FAF2, VCP, AMFR, ZNRF3, CTNNB1, LRP6, GSK3B, FZD6, DVL2 and RNF43 (PubMed:31073040). Interacts with GSK3A (By similarity). Interaction with LGB and SCGB1A1 is controversial (By similarity).|||Endoplasmic reticulum membrane|||Highly expressed in the bone marrow, thymus, spleen and lymphocytes.|||Mice exhibit severely impaired development of all lymphoid lineages, compromised antibody responses to immunization, reduced cytotoxic T-cell killing activity and natural killer (NK) cell function, and resistance to cytomegalovirus infection (PubMed:31073040). T-cells are predisposed to apoptosis and die in response to antigen-specific or homeostatic expansion signals (PubMed:31073040). Impaired differentiation of hematopoietic stem cells into the lymphoid primed multipotent progenitor (LMPP) and common lymphoid progenitor populations that give rise to T-cells, B-cells, and NK cells (PubMed:31073040).|||Plays an essential role in lymphocyte development by negatively regulating the canonical Wnt signaling pathway (PubMed:31073040). In association with UBAC2 and E3 ubiquitin-protein ligase AMFR, promotes the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (PubMed:31073040). LMBR1L stabilizes the beta-catenin destruction complex that is required for regulating CTNNB1 levels (PubMed:31073040). Acts as a LCN1 receptor and can mediate its endocytosis (By similarity). http://togogenome.org/gene/10090:Dtymk ^@ http://purl.uniprot.org/uniprot/P97930|||http://purl.uniprot.org/uniprot/Q6GRA7 ^@ Developmental Stage|||Function|||Similarity|||Subunit ^@ Belongs to the thymidylate kinase family.|||Catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), the immediate precursor for the DNA building block dTTP, with ATP as the preferred phosphoryl donor in the presence of Mg(2+).|||Homodimer.|||Very low mRNA levels in the quiescent cells. As cells exit from G0 to G1 phase, the expression levels gradually increase. http://togogenome.org/gene/10090:Uhmk1 ^@ http://purl.uniprot.org/uniprot/P97343 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||By serum growth factors.|||Interacts with PAM and CDKN1B/p27Kip1 (By similarity). Interacts with stathmin.|||Nucleus|||Upon serum stimulation, phosphorylates CDKN1B/p27Kip1, thus controlling CDKN1B subcellular location and cell cycle progression in G1 phase. May be involved in trafficking and/or processing of RNA (By similarity). http://togogenome.org/gene/10090:Klrb1b ^@ http://purl.uniprot.org/uniprot/Q99JB4 ^@ Domain|||Function|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases leading to down-regulation of cell activation.|||Expressed in NK cells and a subset of T-cells.|||Homodimer; disulfide-linked. Interacts with tyrosine kinase LCK. Binds PTPN6/SHP-1 in a phosphorylation-dependent manner.|||Membrane|||Receptor for CLEC2D/OCIL. Ligand-binding contributes to inhibition of cytotoxic natural killer (NK) cells. May mediate MHC class I-independent 'missing-self' recognition of allografts, tumor cells and virus-infected cells.|||Variants Thr-191 and Ala-191 interfere with binding of the anti-NK1.1 monoclonal antibody PK136 which identifies NK cells from C57BL/6 and SJL but not BALB/c mice by binding Klrb1b and Klrb1c in an allele-dependent manner. Mutagenesis of Thr-191 to Ser-191 restores NK1.1 reactivity to Klrb1b from BALB/c mice. http://togogenome.org/gene/10090:Evi2b ^@ http://purl.uniprot.org/uniprot/Q8VD58 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in myeloid and lymphoid progenitors and increased in mature hematopoietic populations with the highest levels in granulocytes.|||Membrane|||Required for granulocyte differentiation and functionality of hematopoietic progenitor cells through the control of cell cycle progression and survival of hematopoietic progenitor cells. http://togogenome.org/gene/10090:Unc119 ^@ http://purl.uniprot.org/uniprot/B1AQD7|||http://purl.uniprot.org/uniprot/B1AQD9|||http://purl.uniprot.org/uniprot/Q3V299|||http://purl.uniprot.org/uniprot/Q9Z2R6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that captures N-terminally myristoylated target peptides. Phe residues within the hydrophobic beta sandwich are required for myristate binding (By similarity).|||Belongs to the PDE6D/unc-119 family.|||Involved in synaptic functions in photoreceptor cells, the signal transduction in immune cells as a Src family kinase activator, endosome recycling, the uptake of bacteria and endocytosis, protein trafficking in sensory neurons and as lipid-binding chaperone with specificity for a diverse subset of myristoylated proteins. Specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons (PubMed:21642972). Probably plays a role in trafficking proteins in photoreceptor cells (PubMed:17174953). Plays important roles in mediating Src family kinase signals for the completion of cytokinesis via RAB11A.|||Localized in photoreceptor synapses in the outer plexiform layer of the retina.|||May interact with GTP-bound ARL1. Interacts with ARL2 and ARL3 (GTP-bound forms); this promotes the release of myristoylated cargo proteins (By similarity). Found in a complex with ARL3, RP2 and UNC119; RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119. Interacts with NPHP3 (when myristoylated). Interacts with CYS1 (when myristoylated). Interacts with MACIR; interaction only takes place when UNC119 is not liganded with myristoylated proteins (By similarity). Interacts with CABP4; in the absence of calcium. Interacts with DNM1; leading to a decrease of DNM1 GTPase activity. Interacts with LCK; this interaction plays a crucial role in activation of LCK (By similarity). Interacts with FYN (By similarity). Interacts with RAB11A; in a cell cycle-dependent manner (By similarity). Interacts with LYN (via SH2 and SH3 domains); leading to LYN activation (By similarity). Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases. Interacts with CD44 (By similarity). Interacts with KLHL18 (via kelch repeats). Interacts with PPP3CA, PPP3CB and PPP3CC (PubMed:31696965).|||Mice develop a slowly progressive retinal degeneration, characterized by mottling in the fundus, mild thinning of the photoreceptor layer, and increase in apoptosis as early as 6 months, dramatic acceleration at approximately 17 months, and virtual obliteration of the photoreceptors by 20 months. Phenotypes are due to defects in protein trafficking, such as Gnat1 mislocalization.|||Phosphorylation suppresses its interaction with KLHL18 and down-regulates its KLHL18-mediated degradation (PubMed:31696965). Phosphorylated more under light conditions than dark conditions (PubMed:31696965). Dephosphorylated by calcineurin (PubMed:31696965).|||centrosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Vmn1r10 ^@ http://purl.uniprot.org/uniprot/W4VSP8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrrc14 ^@ http://purl.uniprot.org/uniprot/Q8VC16 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRAME family. LRRC14 subfamily.|||Cytoplasm|||Interacts with IKBKB; disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core complex formation and leading to a decrease of IKBKB phosphorylation and NF-kappaB activation. Interacts with CHUK.|||Intron retention.|||Negatively regulates Toll-like receptor-mediated NF-kappa-B signaling by disrupting IKK core complex formation through interaction with IKBKB. http://togogenome.org/gene/10090:Grp ^@ http://purl.uniprot.org/uniprot/Q8R1I2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the bombesin/neuromedin-B/ranatensin family.|||Contrary to wild-type, mutant mice do not display imitative scratching after observing spontaneous scratching behavior in another mouse (PubMed:28280205).|||Detected in peptidergic dorsal root ganglion neurons (at protein level) (PubMed:17653196). Expressed in several dozen neurons throughout the dorsal retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) as well as in scattered cells in the nucleus tractus solitarius and parabrachial nucleus (at protein level) (PubMed:26855425). Within the RTN/pFRG, expressed in neuronal subpopulations distinct from those expressing Nmb (at protein level) (PubMed:26855425). Expressed in L6 corticothalamic neurons (at protein level) (PubMed:34610277). Strongly expressed in several input areas of the auditory cortex including the lateral amygdala, contralateral auditory cortex, temporal association area, perirhinal cortex and auditory thalamic nuclei (at protein level) (PubMed:34610277). Detected in the suprachiasmatic nucleus in the hypothalamus (PubMed:28280205). Detected in a subset of glutamatergic cells in the cortex (PubMed:34610277). Highly expressed both in the lateral nucleus of the amygdala, and in regions sending synaptic projections to the lateral nucleus (PubMed:12526815).|||Induces an itch response through activation of receptors present on mast cells, triggering mast cell degranulation.|||Secreted|||Stimulates the release of gastrin and other gastrointestinal hormones (By similarity). Contributes to the perception of prurient stimuli and to the transmission of itch signals in the spinal cord that promote scratching behavior (PubMed:28280205, PubMed:17653196, PubMed:26658875). Contributes primarily to nonhistaminergic itch sensation (PubMed:28280205). In one study, shown to act in the amygdala as part of an inhibitory network which inhibits memory specifically related to learned fear (PubMed:12526815). In another study, shown to act on vasoactive intestinal peptide (VIP)-expressing cells in the auditory cortex, most likely via extrasynaptic diffusion from local and long-range sources, to mediate disinhibition of glutamatergic cells via VIP cell-specific GRPR signaling which leads to enhanced auditory fear memories (PubMed:34610277). Contributes to the regulation of food intake (PubMed:12176666). Inhibits voltage-gated sodium channels but enhances voltage-gated potassium channels in hippocampal neurons (By similarity). Contributes to the induction of sighing by acting directly on the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity (PubMed:26855425).|||neuron projection|||secretory vesicle lumen http://togogenome.org/gene/10090:Fezf1 ^@ http://purl.uniprot.org/uniprot/Q0VDQ9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ At 8.0 dpc expressed in prospective forebrain region. At 12.5 dpc, detected in the olfactory epithelium, septum, roof of the telencephalon, amygdala, prethalamus and hypothalamus. Expression was barely detected in the vomeronasal organs at 12.5 dpc. At 15.5 dpc, detected weakly in the olfactory epithelium, amygdala and hypothalamusat 15.5 dpc. Expression was not detected in the olfactory bulb or in the ganglionic eminences, where the interneuron progenitors of the olfactory bulb are generated.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Null mutants were born alive but most of them died within one day. The olfactory bulbs were smaller than those of their wild-type at 18.5 dpc and at postnatal day 1. At 14.5 dpc and 18 dpc no abnormalities in the morphology of the telencephalon or diencephalon were detected. There seems to be a redundant role for FEZF1 and FEZF2 in diencephalon development.|||Transcription repressor. Involved in the axonal projection and proper termination of olfactory sensory neurons (OSN). Plays a role in rostro-caudal patterning of the diencephalon and in prethalamic formation. Expression is required in OSN to cell-autonomously regulate OSN axon projections. Regulates non-cell-autonomously the layer formation of the olfactory bulb development and the interneurons. May be required for correct rostral migration of the interneuron progenitors. http://togogenome.org/gene/10090:Fam210b ^@ http://purl.uniprot.org/uniprot/Q9D8B6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAM210 family.|||Expressed in late erythroblast differentiation stages (PubMed:26968549).|||Mitochondrion|||Mitochondrion outer membrane|||Plays a role in erythroid differentiation. Involved in cell proliferation and tumor cell growth suppression. Involved in the metabolic reprogramming of cancer cells in a PDK4-dependent manner.|||Up-regulated by the erythroid transcription factor GATA1 (PubMed:26968549). http://togogenome.org/gene/10090:Ngly1 ^@ http://purl.uniprot.org/uniprot/Q9JI78 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transglutaminase-like superfamily. PNGase family.|||Binds 1 zinc ion per subunit.|||Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Interacts with the proteasome components RAD23B and PSMC1. Interacts with directly with VCP. Interacts with DERL1, bringing it close to the endoplasmic reticulum membrane. Interacts with SAKS1.|||Cytoplasm|||Inhibited by Z-VAD-fmk, a well-known caspase inhibitor, which inhibits enzyme activity through covalent binding of the carbohydrate to the single Cys-306 residue.|||Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.|||The PUB domain mediates the interaction with VCP.|||Ubiquitously expressed with highest level in testis. http://togogenome.org/gene/10090:Or11l3 ^@ http://purl.uniprot.org/uniprot/Q5NCD0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or1e17 ^@ http://purl.uniprot.org/uniprot/Q7TRX4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5au1 ^@ http://purl.uniprot.org/uniprot/B2RVX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Psd ^@ http://purl.uniprot.org/uniprot/Q5DTT2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PSD family.|||Cell membrane|||Cell projection|||Cleavage furrow|||Expressed in embryonic, early postnatal and adult brain, with expression up-regulated at postnatal day 4-8 and down-regulated in adults. Isoform 2 expression is up-regulated in adults.|||Guanine nucleotide exchange factor for ARF6 (By similarity). Isoform 2 and isoform 3 induce cytoskeletal remodeling, but lead to distinct morphological changes in HeLa cells: isoform 2 induces cell elongation and formation of actin-rich protrusions, whereas isoform 3 promotes the formation of membrane ruffles and loss of stress fibers (PubMed:19494129).|||Highest expression detected in brain and some expression detected also in uterus, stomach, ovary and intestine, with isoform 2 being expressed at the highest levels. In the brain, isoform 1 is highly expressed in the strata oriens, radiatum, lacunosum-moleculare of the hippocampal CA1-3 regions and the dentate molecular layer of the hippocampal formation, with lower levels detected in the neuronal cell layers and the stratum lucidum (at protein level). Not detected in tongue, thymus, spleen, lung, heart, liver and kidney.|||Interacts with ACTN1 (PubMed:17298598). Interacts (ARF6-bound form) with KCNK1; does not interact with KCNK1 in the absence of ARF6 (PubMed:15540117).|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||ruffle|||ruffle membrane http://togogenome.org/gene/10090:Mtmr12 ^@ http://purl.uniprot.org/uniprot/Q80TA6 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an adapter for the myotubularin-related phosphatases (PubMed:23818870). Regulates phosphatase MTM1 protein stability and possibly its intracellular location (PubMed:23818870). By stabilizing MTM1 protein levels, required for skeletal muscle maintenance but not for myogenesis (PubMed:23818870).|||Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 391 in the dsPTPase catalytic loop and does not have phosphatase activity.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Expressed in skeletal muscles (at protein level).|||Expression increases during skeletal muscle cell differentiation followed by a decrease at later stages of differentiation.|||Heterodimer with lipid phosphatase MTM1 (PubMed:23818870). Heterodimer with lipid phosphatase MTMR2 (By similarity).|||Sarcoplasmic reticulum|||sarcomere http://togogenome.org/gene/10090:Ppp2r2a ^@ http://purl.uniprot.org/uniprot/Q3TT94|||http://purl.uniprot.org/uniprot/Q6P1F6|||http://purl.uniprot.org/uniprot/Q9CWU3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the phosphatase 2A regulatory subunit B family.|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with TP53 (By similarity). Interacts with IER5 (By similarity). Interacts with MFHAS1; the interaction is direct (By similarity). Interacts with PABIR1/FAM122A (By similarity). Interacts with CRTC3 (PubMed:30611118).|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Essential for serine/threonine-protein phosphatase 2A-mediated dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint. http://togogenome.org/gene/10090:Ttc21a ^@ http://purl.uniprot.org/uniprot/Q8C0S4 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the TTC21 family.|||Interacts with IFT20. Interacts with IFT52. Interacts with IFT140.|||Intraflagellar transport (IFT)-associated protein required for spermatogenesis (PubMed:30929735). Required for sperm flagellar formation and intraflagellar transport (PubMed:30929735).|||Male mice display strongly reduced fertility (PubMed:30929735). Spermatozoa show significantly reduced motility and morphologic abnormalities are observed, such as primarily tailless spermatozoa with an abnormal head-tail junction, as well as short and coiled flagella (PubMed:30929735). Structural abnormalities of the connecting piece are observed during spermiogenesis and multiple structural defects of the flagella, with a greatly increased percentage of flagella exhibiting abnormal principal pieces and end pieces (PubMed:30929735). Axonemal structural abnormalities, such as abnormal bulges, extra peripheral microtubule doublets, lack of central-pair microtubules, absent dynein arms, and abnormal arrangement of the 9 peripheral microtubule doubles, are also frequently observed (PubMed:30929735). http://togogenome.org/gene/10090:Tvp23b ^@ http://purl.uniprot.org/uniprot/Q9D8T4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TVP23 family.|||Membrane http://togogenome.org/gene/10090:Islr ^@ http://purl.uniprot.org/uniprot/Q6GU68 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected at all stages of development and more abundant in the latter period.|||Detected in thyroid, heart, retina and spinal cord.|||Secreted http://togogenome.org/gene/10090:Mrgpra4 ^@ http://purl.uniprot.org/uniprot/Q91WW2|||http://purl.uniprot.org/uniprot/W8W3F5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed in a subset of sensory neurons that includes nociceptors. Expressed in the subclass of non-peptidergic sensory neurons that are IB4(+) and VR1(-).|||Membrane|||Orphan receptor. May be a receptor for RFamide-family neuropeptides such as NPFF and NPAF, which are analgesic in vivo. May regulate nociceptor function and/or development, including the sensation or modulation of pain. http://togogenome.org/gene/10090:Zpbp ^@ http://purl.uniprot.org/uniprot/B7ZP49|||http://purl.uniprot.org/uniprot/Q5NC84|||http://purl.uniprot.org/uniprot/Q62522 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Barely detectable at 11 days postpartum (dpp), very strong signal from 20 dpp until adulthood (PubMed:19204925). Expressed from the mid-pachytene spermatocyte stage to the early elongating spermatid stage (PubMed:17664285, PubMed:19204925).|||Belongs to the zona pellucida-binding protein Sp38 family.|||Expressed in testis (at protein level) (PubMed:19204925). Expressed in male germ cells (PubMed:17664285).|||Male mice are infertile with abnormal round-headed sperm morphology and no forward sperm motility.|||N-glycosylated.|||Plays a role in acrosome compaction and sperm morphogenesis. Is implicated in sperm-oocyte interaction during fertilization.|||Secreted|||acrosome|||acrosome membrane http://togogenome.org/gene/10090:Tmed4 ^@ http://purl.uniprot.org/uniprot/Q8R1V4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the EMP24/GP25L family.|||By brefeldin A, oxidative stress and heat shock, but not by tunicamycin, hypersomotic stress or serum starvation.|||Endoplasmic reticulum membrane|||Involved in vesicular protein trafficking, mainly in the early secretory pathway. Involved in the maintenance of the Golgi apparatus. Appears to play a role in the biosynthesis of secreted cargo including processing. Involved in endoplasmic reticulum stress response. May play a role in the regulation of heat-shock response and apoptosis (By similarity). http://togogenome.org/gene/10090:Rab40b ^@ http://purl.uniprot.org/uniprot/Q8VHP8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Fam186a ^@ http://purl.uniprot.org/uniprot/Q9D9R9 ^@ Similarity ^@ Belongs to the FAM186 family. http://togogenome.org/gene/10090:Cetn4 ^@ http://purl.uniprot.org/uniprot/Q8K4K1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the centrin family.|||Ca(2+)-binding protein that may be involved in basal body assembly or in a subsequent step of ciliogenesis.|||Cytoplasm|||In brain, specifically expressed in ciliated cells. In retina, expression is localized to the connecting cilium and basal body of photoreceptors (at protein level). Highly expressed in brain, kidney, lung, retina and ovary, and weakly expressed in spleen. Not detected in testis, colon, stomach, thymus, skeletal muscle, heart, intestine or liver.|||Interacts with G-protein beta-gamma dimers in a calcium-dependent manner.|||Phosphorylated on Thr-134 by casein kinase II (CK2) in a light-dependent manner.|||The fourth EF-hand domain has been proven to bind calcium.|||centriole http://togogenome.org/gene/10090:Or2g7 ^@ http://purl.uniprot.org/uniprot/Q8VFC1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hexim1 ^@ http://purl.uniprot.org/uniprot/Q8R409 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HEXIM family.|||Cytoplasm|||Homooligomer and heterooligomer with HEXIM2; probably dimeric. Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1). Interacts with the N-CoR complex through NCOR1. Interacts with ESR1 and NR3C1. May interact with NF-kappa-B through RELA. Interacts with CCNT2; mediates formation of a tripartite complex with KPNA2. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 non-coding RNA.|||Nucleus|||The coiled-coil domain mediates oligomerization.|||Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. May also regulate NF-kappa-B, ESR1, NR3C1 and CIITA-dependent transcriptional activity. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.|||Up-regulated by HMBA (hexamethylene bisacetamide).|||Widely expressed with higher expression in heart, skeletal muscle and brain (at protein level). http://togogenome.org/gene/10090:Or5aq7 ^@ http://purl.uniprot.org/uniprot/Q7TS20 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arglu1 ^@ http://purl.uniprot.org/uniprot/Q3UL36 ^@ Sequence Caution|||Similarity ^@ Belongs to the UPF0430 family.|||Chimeric cDNA. http://togogenome.org/gene/10090:Galnt10 ^@ http://purl.uniprot.org/uniprot/Q5SQF9|||http://purl.uniprot.org/uniprot/Q6P9S7 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ According to experiments made in rat, this enzyme is unable to transfer GalNAc onto serine or threonine residue on the protein receptor, but instead requires the prior addition of a GalNAc on a peptide before adding additional GalNAc moieties, thereby acting as a glycopeptide transferase.|||Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward Muc5Ac and EA2 peptide substrates (By similarity).|||Expressed at higher level than GALNT9. In the developing hindbrain region of 14.5 dpc embryos it accumulates in the rapidly dividing, undifferentiated ventricular zone adjacent to the pons. It also accumulates in the regions immediately rostral and caudal to the dorsal rhombic lips differentiating into the cerebellum. Not expressed in the developing choroid plexus.|||Golgi apparatus membrane|||Membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Espnl ^@ http://purl.uniprot.org/uniprot/Q3UYR4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to but does not cross-link actin. Required for the formation and maintenance of inner ear hair cell stereocilia and staircase formation. Essential for normal hearing.|||Expressed in inner ear hair cells (PubMed:25582750). Expressed in utricle hair bundles (at protein level). Expressed in choclea (at protein level) (PubMed:26926603).|||Interacts with MYO3A (via C-terminus). Interacts with MYO3B (via C-terminus).|||stereocilium http://togogenome.org/gene/10090:B3galt2 ^@ http://purl.uniprot.org/uniprot/O54905 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-galactosyltransferase that transfers galactose from UDP-galactose to substrates with a terminal beta-N-acetylglucosamine (beta-GlcNAc) residue. Can also utilize substrates with a terminal galactose residue, albeit with lower efficiency. Involved in the biosynthesis of the carbohydrate moieties of glycolipids and glycoproteins.|||Detected in brain and heart.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Prss35 ^@ http://purl.uniprot.org/uniprot/Q8C0F9 ^@ Caution|||Developmental Stage|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although related to peptidase S1 family, lacks the conserved active Ser residue in position 342 which is replaced by a Thr, suggesting that it has no protease activity.|||Belongs to the peptidase S1 family.|||Expression is progesterone-dependent regulation prior to follicle rupture.|||In ovary, it localizes to the theca cells of pre-antral follicles, the theca and granulosa cells of pre-ovulatory and ovulatory follicles, as well as to the developing corpus luteum.|||Increases around the time of ovulation and remained elevated in the developing corpus luteum.|||Secreted http://togogenome.org/gene/10090:Cdk9 ^@ http://purl.uniprot.org/uniprot/Q99J95 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation by Thr-186 phosphorylation is calcium Ca(2+) signaling pathway-dependent; actively inactivated by dephosphorylation mediated by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-44 and Lys-48 (By similarity).|||Autophosphorylation at Thr-186, Ser-347, Thr-350, Ser-353, Thr-354 and Ser-357 triggers kinase activity by promoting cyclin and substrate binding upon conformational changes. Thr-186 phosphorylation requires the calcium Ca(2+) signaling pathway, including CaMK1D and calmodulin. This inhibition is relieved by Thr-29 dephosphorylation. Phosphorylation at Ser-175 inhibits kinase activity. Can be phosphorylated on either Thr-362 or Thr-363 but not on both simultaneously (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Associates with CCNT1/cyclin-T1, CCNT2/cyclin-T2 (isoform A and isoform B) or CCNK/cyclin-K to form active P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31 and is part of the super elongation complex (SEC). Component of a complex which is composed of at least 5 members: HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H, and NCL/nucleolin. Associates with UBR5 and forms a transcription regulatory complex composed of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma fibrinogen/FGG) by recruiting their promoters. Component of the 7SK snRNP inactive complex which is composed of at least 8 members: P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, LARP7, BCDIN3, SART3 proteins and 7SK and U6 snRNAs. This inactive 7SK snRNP complex can also interact with NCOR1 and HDAC3, probably to regulate CDK9 acetylation. Release of P-TEFb from P-TEFb/7SK snRNP complex requires both PP2B to transduce calcium Ca(2+) signaling in response to stimuli (e.g. UV or hexamethylene bisacetamide (HMBA)), and PPP1CA to dephosphorylate Thr-186. This released P-TEFb remains inactive in the pre-initiation complex with BRD4 until new Thr-186 phosphorylation occurs after the synthesis of a short RNA. Interacts with BRD4; to target chromatin binding. Interacts with JMJD6. Interacts with activated nuclear STAT3 and RELA/p65. Binds to AR and MYOD1. Forms a complex composed of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes (By similarity). The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active) (PubMed:22767893). Interacts with HSF1 (By similarity). Interacts with TBX21 (PubMed:27292648). Interacts with WDR43 (PubMed:31128943). Interacts with ZMYND8; the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (By similarity).|||Cytoplasm|||Dephosphorylation of Thr-186 by PPM1A and PPM1B blocks CDK9 activity and may lead to CDK9 proteasomal degradation. However, PPP1CA-mediated Thr-186 dephosphorylation is required to release P-TEFb from its inactive P-TEFb/7SK snRNP complex. Dephosphorylation of C-terminus Thr and Ser residues by protein phosphatase-1 (PP1) triggers CDK9 activity (By similarity).|||Expressed at high levels in brain and kidney.|||N6-acetylation of Lys-44 promotes kinase activity, whereas acetylation of both Lys-44 and Lys-48 mediated by PCAF/KAT2B and GCN5/KAT2A reduces kinase activity. The acetylated form associates with PML bodies in the nuclear matrix and with the transcriptionally silent HIV-1 genome; deacetylated upon transcription stimulation. Deacetylated by SIRT7, promoting the kinase activity and subsequent 'Ser-2' phosphorylation of the C-terminal domain (CTD) of RNA polymerase II.|||Nucleus|||PML body|||Polyubiquitinated and thus activated by UBR5. This ubiquitination is promoted by TFIIS/TCEA1 and favors 'Ser-2' phosphorylation of RPB1/POLR2A CTD (By similarity).|||Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation. Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity. http://togogenome.org/gene/10090:Hs6st3 ^@ http://purl.uniprot.org/uniprot/Q149R8|||http://purl.uniprot.org/uniprot/Q3UTM4|||http://purl.uniprot.org/uniprot/Q9QYK4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.|||Belongs to the sulfotransferase 6 family.|||Membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Tnr ^@ http://purl.uniprot.org/uniprot/Q8BYI9 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tenascin family.|||Brain-specific.|||Contains N-linked oligosaccharides with a sulfated carbohydrate structures (By similarity). Contains N-linked oligosaccharides, O-linked sialylated structures and O-linked chondroitin sulfate glycosaminoglycans.|||Interacts with BCAN and ACAN in a calcium-dependent manner. Interacts with SCN2B, PTPRZ1, and CSPG3 (By similarity). Forms oligomers. Isoforms 1 and 2 form respectively trimeric (tribrachion) and dimeric kink-armed rodlike structures, which are linked by disulfide bridges. Interacts with CNTN1, TNC and FN1.|||Isoform 1 is barely detectable at 17 dpc and increases in intensity until postnatal day 15, when it reaches adult levels. Isoform 2 is detectable from postnatal day 5 and reaches adult levels also at postnatal day 15.|||Knockout mice display alterations of the extracellular matrix, and decreased axonal conduction velocities in the CNS.|||Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. Theses interactions can influence cellular behavior by either evoking a stable adhesion and differentiation, or repulsion and inhibition of neurite growth. Binding to cell surface gangliosides inhibits RGD-dependent integrin-mediated cell adhesion and results in an inhibition of PTK2/FAK1 (FAK) phosphorylation and cell detachment. Binding to membrane surface sulfatides results in a oligodendrocyte adhesion and differentiation. Interaction with CNTN1 induces a repulsion of neurons and an inhibition of neurite outgrowth. Interacts with SCN2B may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier. TNR-linked chondroitin sulfate glycosaminoglycans are involved in the interaction with FN1 and mediates inhibition of cell adhesion and neurite outgrowth. The highly regulated addition of sulfated carbohydrate structure may modulate the adhesive properties of TNR over the course of development and during synapse maintenance (By similarity).|||The EGF-like domains mediate interaction with CNTN1. The fibronectin type-III domains 3-5 mediate interaction with BCAN. The fibronectin type-III domains 1-2 and 7-9 mediate interaction with SCN2B (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Btbd18 ^@ http://purl.uniprot.org/uniprot/A0A0A6YY25 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed during pachytene in testis: accumulates in early pachytene cells (stages I-VII), declines in late pachytene cells (stages VIII-X) and disappears in diplotene cells (stage XI) (at protein level). Expressed from spermatogonia to spermatids, with trace expression in mature spermatozoa and somatic Sertoli cells.|||Expressed in testis.|||Mice are viable but show male sterility due to defects in spermatogenesis. Retrotransposons are derepressed due to DNA demethylation. Defects are caused by impaired piRNA biogenesis.|||Nucleus|||Specifically required during spermatogenesis to promote expression of piRNA precursors. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons, which is essential for the germline integrity. Acts by facilitating transcription elongation at piRNA loci during pachytene. http://togogenome.org/gene/10090:Nlrp14 ^@ http://purl.uniprot.org/uniprot/Q6B966 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NLRP family.|||Cytoplasm|||Detected in adult ovary and testis. Detected in oocytes and in germ cell elements in seminiferous tubules in adult testis (at protein level).|||May be involved in inflammation and spermatogenesis.|||Not detected in ovaries from neonates. First detected in ovaries three days after birth, and expression in ovaries increases dramatically to reach a much higher level eight days after birth. http://togogenome.org/gene/10090:Sumo3 ^@ http://purl.uniprot.org/uniprot/G3UZA7|||http://purl.uniprot.org/uniprot/Q9Z172 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin family. SUMO subfamily.|||Cleavage of precursor form by SENP1, SENP2 or SENP5 is necessary for function.|||Cytoplasm|||Interacts with SAE2 and UBE2I. Covalently attached to a number of proteins. Interacts with USP25 (via ts SIM domain); the interaction sumoylates USP25 and inhibits its ubiquitin hydrolyzing activity (By similarity). Interacts with BMAL1.|||Nucleus|||PML body|||Polymeric chains can be formed through Lys-11 cross-linking.|||Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4. Plays a role in the regulation of sumoylation status of SETX (By similarity). http://togogenome.org/gene/10090:Crisp2 ^@ http://purl.uniprot.org/uniprot/P16563 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRISP family.|||Interacts with NSUN4 isoform 3.|||May regulate some ion channels' activity and therebye regulate calcium fluxes during sperm capacitation.|||Secreted|||Testis. http://togogenome.org/gene/10090:Insyn1 ^@ http://purl.uniprot.org/uniprot/Q8CD60 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the INSYN1 family.|||Component of the protein machinery at the inhibitory synapses, probably acting as a scaffold. Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization. This synaptic inhibition is fundamental for the functioning of the central nervous system, shaping and orchestrating the flow of information through neuronal networks to generate a precise neural code.|||Interacts with GPHN.|||Postsynaptic density http://togogenome.org/gene/10090:Or2a7 ^@ http://purl.uniprot.org/uniprot/P34984|||http://purl.uniprot.org/uniprot/Q0VAZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor.|||Olfactory epithelium. http://togogenome.org/gene/10090:Sycp2 ^@ http://purl.uniprot.org/uniprot/Q9CUU3 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SYCP2 family.|||Chromosome|||Component of the lateral elements of synaptonemal complexes (PubMed:16717126). Heterodimer with SYCP3 (PubMed:16717126). Interacts with SMC1A and SMC3 (By similarity). Interacts with TEX11 (PubMed:18316482).|||Detected in testis and spermatocytes (at protein level).|||Intron retention.|||Major component of the axial/lateral elements of synaptonemal complexes (SCS) during meiotic prophase. Plays a role in the assembly of synaptonemal complexes (PubMed:16717126). Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility (PubMed:16717126). Required for insertion of SYCP3 into synaptonemal complexes (PubMed:16717126). May be involved in the organization of chromatin by temporarily binding to DNA scaffold attachment regions. Requires SYCP3, but not SYCP1, in order to be incorporated into the axial/lateral elements.|||Mice appear healthy, but males are completely sterile, due to defective meiotic chromosome synapsis during spermatocyte development. Testes weight is much reduced in mutant mice. Females display reduced fertility.|||Nucleus|||Phosphorylated. http://togogenome.org/gene/10090:Alox12e ^@ http://purl.uniprot.org/uniprot/P55249|||http://purl.uniprot.org/uniprot/Q5F2E4 ^@ Activity Regulation|||Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Arachidonate 12-lipoxygenase activity is decreased when the pH decreases from 7.4 to 6.0.|||Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:8798535, PubMed:9037187, PubMed:11256953). Shows increasing catalytic activity within the series arachidonic acid < 5,8,11-eicosatrienoic acid < linoleic acid < 8,11,14-eicosatrienoic acid (PubMed:11256953).|||Cytoplasm|||Expressed in epidermis.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Was originally thought to be an arachidonate 8-lipoxygenase and was called LOX8. http://togogenome.org/gene/10090:Zcchc18 ^@ http://purl.uniprot.org/uniprot/Q8VD24 ^@ Similarity ^@ Belongs to the ZCCHC12 family. http://togogenome.org/gene/10090:Crip1 ^@ http://purl.uniprot.org/uniprot/P63254 ^@ Function ^@ Seems to have a role in zinc absorption and may function as an intracellular zinc transport protein. http://togogenome.org/gene/10090:2300009A05Rik ^@ http://purl.uniprot.org/uniprot/Q0VG49 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:P2rx2 ^@ http://purl.uniprot.org/uniprot/Q8K3P1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the P2X receptor family.|||Cell membrane|||Homotrimer and heterotrimer; functional P2XRs are organized as homomeric and heteromeric trimers.|||In skeletal muscle, strongly expressed in postnatal day 3 (P3), P7 and P15 muscles. Expression is not maintained in P21 in adult skeletal muscle (at protein level).|||Ion channel gated by extracellular ATP involved in a variety of cellular responses, such as excitatory postsynaptic responses in sensory neurons, neuromuscular junctions (NMJ) formation, hearing, perception of taste and peristalsis. In the inner ear, regulates sound transduction and auditory neurotransmission, outer hair cell electromotility, inner ear gap junctions, and K(+) recycling. Mediates synaptic transmission between neurons and from neurons to smooth muscle.|||Mice show small differences in body weight, but are visibly and histopathologically normal for up to 1 year of age. Simultaneous knockout of P2rx2 and P2rx3 results in reduced pain-related behaviors in response to intraplantar injection of formalin and reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension. Neurons have minimal to no response to ATP (PubMed:15961431). P2rx2 null mice show impaired peristalsis in ileal segments of small intestine (PubMed:12937291). P2rx2 null mice show disorganized neuromuscular junctions (NMJ) with misapposition of nerve terminals and post-synaptic AChR expression localization, reduction of the density of post-synaptic and increased end-plate fragmentation. These changes in NMJ structure are associated with muscle fiber atrophy and an increase in the proportion of fast type muscle fibers (PubMed:17706883). P2rx2 null mice display age-related hearing loss: in the absence of exposure to noise, auditory thresholds are normal until at least age 19-23 week. Then, mice develop severe progressive hearing loss, and their early exposure to continuous moderate noise leads to high-frequency hearing loss as young adults (PubMed:23345450). Simultaneous knockout of P2rx2 and P2rx3 results in defects in taste responses in the taste nerves and reduced behavioral responses to sweeteners, glutamate and bitter substances (PubMed:16322458). http://togogenome.org/gene/10090:Klhdc1 ^@ http://purl.uniprot.org/uniprot/Q80YG3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of a CRL5 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL5, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter KLHDC1.|||Substrate-recognition component of a Cul5-RING (CRL5) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL5(KLHDC1) complex mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine.|||cytosol http://togogenome.org/gene/10090:Commd7 ^@ http://purl.uniprot.org/uniprot/Q8BG94 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA. Interacts with CCDC22, CCDC93, SCNN1B, CUL7.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Associates with the NF-kappa-B complex and suppresses its transcriptional activity. http://togogenome.org/gene/10090:Ankrd39 ^@ http://purl.uniprot.org/uniprot/Q9D2X0 ^@ Similarity ^@ Belongs to the ANKRD39 family. http://togogenome.org/gene/10090:Tgfb2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXU9|||http://purl.uniprot.org/uniprot/P27090|||http://purl.uniprot.org/uniprot/Q3TWH5|||http://purl.uniprot.org/uniprot/Q8CDZ9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Homodimer; disulfide-linked.|||Interacts with Transforming growth factor beta-2 (TGF-beta-2) chain; interaction is non-covalent and maintains (TGF-beta-2) in a latent state (By similarity). Interacts with LRRC32/GARP; leading to regulate activation of TGF-beta-2 (By similarity). Interacts with NREP; the interaction results in a decrease in TGFB2 autoinduction (PubMed:14985127).|||Interacts with the serine proteases, HTRA1 and HTRA3 (PubMed:15206957, PubMed:14973287). Interacts with ASPN (By similarity). Interacts with MFAP5 (PubMed:23963447).|||Multifunctional protein that regulates various processes such as angiogenesis and heart development (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains remain non-covalently linked rendering TGF-beta-2 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2 and maintain it in a latent state during storage in extracellular milieus (By similarity). Once activated following release of LAP, TGF-beta-2 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).|||Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.|||Required to maintain the Transforming growth factor beta-2 (TGF-beta-2) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-2 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-2.|||Secreted|||The precursor proprotein is cleaved in the Golgi apparatus to form Transforming growth factor beta-2 (TGF-beta-2) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-2 inactive.|||Transforming growth factor beta-2: Homodimer; disulfide-linked (By similarity). Transforming growth factor beta-2: Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Lmnb1 ^@ http://purl.uniprot.org/uniprot/P14733 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ B-type lamins undergo a series of modifications, such as farnesylation and phosphorylation. Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations.|||Belongs to the intermediate filament family.|||Homodimer. Interacts with lamin-associated polypeptides IA, IB and 2. Interacts with SPAG4 and SEPT12 (By similarity).|||Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin.|||Nucleus lamina|||The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively. http://togogenome.org/gene/10090:ND6 ^@ http://purl.uniprot.org/uniprot/P03925|||http://purl.uniprot.org/uniprot/Q7JCY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 6 family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:9707444). Essential for the catalytic activity and assembly of complex I (PubMed:9707444).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.|||Mitochondrion inner membrane|||Mitochondrion membrane http://togogenome.org/gene/10090:Mnat1 ^@ http://purl.uniprot.org/uniprot/P51949 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates primarily with CDK7 and cyclin H to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.|||Nucleus|||Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. http://togogenome.org/gene/10090:C3ar1 ^@ http://purl.uniprot.org/uniprot/O09047|||http://purl.uniprot.org/uniprot/Q5U7A4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the chemokine-like receptor (CMKLR) family.|||Cell membrane|||Detected in varying levels in all tissues examined except the spleen. Especially abundant in heart and lung.|||Interacts with VGF-derived peptide TLQP-21.|||Membrane|||Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production. http://togogenome.org/gene/10090:Lyg1 ^@ http://purl.uniprot.org/uniprot/Q0VE18|||http://purl.uniprot.org/uniprot/Q9D7Q0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 23 family.|||Secreted http://togogenome.org/gene/10090:Zbtb7c ^@ http://purl.uniprot.org/uniprot/Q8VCZ7 ^@ Function ^@ May be a tumor suppressor gene. http://togogenome.org/gene/10090:Or7d9 ^@ http://purl.uniprot.org/uniprot/E9PVX1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H3c8 ^@ http://purl.uniprot.org/uniprot/P68433 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (By similarity).|||This histone is only present in mammals.|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Pik3c2a ^@ http://purl.uniprot.org/uniprot/F8VPL2|||http://purl.uniprot.org/uniprot/Q61194 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by clathrin (By similarity). Only slightly inhibited by wortmannin and LY294002. Activated by insulin.|||Belongs to the PI3/PI4-kinase family.|||Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.|||Ca(2+) or Mg(2+). Mn(2+) cannot be used.|||Cell membrane|||Chronic renal failure and kidney lesions. Affects podocyte morphology and function.|||Cytoplasm|||Expressed in brain (at protein level) (PubMed:22648168). Detected in podocytes (PubMed:20974805).|||Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (By similarity).|||Interacts with ERBB2 and EGFR (By similarity). Interacts with clathrin trimers (By similarity). Interacts with SBF2/MTMR13 (PubMed:22648168).|||Nucleus|||Phosphorylated on Ser-261 during mitosis and upon UV irradiation; which does not change enzymatic activity but leads to proteasomal degradation (By similarity). Phosphorylated upon insulin stimulation; which may lead to enzyme activation.|||clathrin-coated vesicle|||trans-Golgi network http://togogenome.org/gene/10090:Rbbp5 ^@ http://purl.uniprot.org/uniprot/Q8BX09 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (By similarity). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (By similarity). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (By similarity). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (By similarity). Interacts with ZNF335 (PubMed:23178126). Interacts with ASH2L; the interaction is direct (By similarity). Interacts with WDR5; the interaction is direct (By similarity). Components of the ZNF335-RBBP5-ASH2L-WDR5 histone methylation complex may associate with components of a nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (By similarity). Within this complex interacts with EMSY (By similarity). Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5 (PubMed:21335234). Interacts with SETD1A (By similarity). Interacts with WDR82 (By similarity).|||In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (PubMed:21335234). Does not affect ES cell self-renewal (PubMed:21335234). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (By similarity). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (By similarity). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (By similarity).|||Nucleus http://togogenome.org/gene/10090:Isoc1 ^@ http://purl.uniprot.org/uniprot/Q91V64 ^@ Similarity ^@ Belongs to the isochorismatase family. http://togogenome.org/gene/10090:Rora ^@ http://purl.uniprot.org/uniprot/P51448|||http://purl.uniprot.org/uniprot/Q3U1P4 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Defects in Rora are the cause of the staggerer (SG) mutant phenotype which is characterized by disturbance of Purkinje cell development and immune system functioning. This phenotype exhibits lower body weight, reduced adiposity, decreased plasma cholesterol, triglyceride and apolipoprotein CIII levels, and is resistant to diet-induced obesity. Also has abnormal circadian rhythms.|||Expressed in cerebellum, heart, liver, lung, kidney, retina and brown and white adipose tissues. Expressed in the subset of mature Th17 cells.|||In T(H) cells, induced upon antigen receptor ligation in the presence of IL6 and TGB1 (via STAT3). Oscillates diurnally in central nervous system. In liver, Isoform 1 oscillates diurnally but not isoform 4.|||In cerebellum, expression begins at 12.5 dpc. In the developing retina, first expressed at 17 dpc in the ganglion cell layer. At P3, expressed in the inner border of the neuroblasitic border (presumptive amacrine cells). By P6, levels increase in developing cones. Expression found in the presumptive bipolar cells by P9. During adipocyte differentiation, expression gradually increases.|||Monomer. Interacts (via the DNA-binding domain) with HIF1A; the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interacts with CEBPB; the interaction disrupts the interaction CEBPB:EP300. Interacts with the coactivators NCOA2, PPARGC1A (via LXXLL motif), EP300 and MED1. Interacts with the corepressor NCOR1. Interacts with MAGED1 and CTNNB1. Interacts with CRY1 and PER2. Interacts (via AF-2 motif) with PROX1. Interacts with NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3 (via LXXLL motif) (By similarity).|||Monomethylated at Lys-38 by EZH2, this creates a degron recognized by a DCX (DDB1-DCAF1/VPRBP-CUL4A-RBX1) E3 ubiquitin ligase complex.|||Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC1 and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.|||Nucleus|||Phosphorylation by conventional PKCs in neurons inhibits transcriptional activity. Phosphorylated on Thr-183 by MAPK1/ERK1 in vitro.|||Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2, PIAS3, PIAS4 but not PIAS1, enhances the transcriptional activity. Desumoylated by SENP1.|||The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs.|||Ubiquitinated, leading to its degradation by the proteasome. Proteasomal degradation is required for efficient transcriptional activity and is prevented by HR. http://togogenome.org/gene/10090:Stx17 ^@ http://purl.uniprot.org/uniprot/Q9D0I4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||COPII-coated vesicle membrane|||Dephosphorylation by PTPN2; regulates exit from the endoplasmic reticulum (By similarity). Phosphorylated at Tyr-156 probably by ABL1 (PubMed:23006999).|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Forms a SNARE complex composed of VAMP8, SNAP29 and STX17 involved in fusion of autophagosome with lysosome (By similarity). May interact with VTI1B (By similarity). Probably interacts with BET1, SCFD1 and SEC22B (By similarity). Interacts with PTPN2 and ABL1; involved in STX17 phosphorylation (By similarity). Interacts with COPB1 (By similarity). Interacts with TMED9 and TMED10; the interaction is direct (By similarity). Interacts with VAMP7 (PubMed:23217709). Interacts with RUBCNL/PACER; promoting targeting of RUBCNL/PACER to autophagosome (By similarity). Interacts with VAMP8, SNAP29, VPS39 and VPS41; these interactions are increased in the absence of TMEM39A (By similarity). Interacts with IRGM; promoting STX17 recruitment to autophagosomes (By similarity). Interacts with ATG8 proteins GABARAP and MAP1LC3B (By similarity).|||Mitochondrion membrane|||SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. STX17 is a SNARE of the autophagosome involved in autophagy through the direct control of autophagosome membrane fusion with the lysosome membrane. May also play a role in the early secretory pathway where it may maintain the architecture of the endoplasmic reticulum-Golgi intermediate compartment/ERGIC and Golgi and/or regulate transport between the endoplasmic reticulum, the ERGIC and the Golgi (By similarity).|||Smooth endoplasmic reticulum membrane|||autophagosome membrane|||cytosol http://togogenome.org/gene/10090:Cacnb3 ^@ http://purl.uniprot.org/uniprot/A0A2U3TZ49|||http://purl.uniprot.org/uniprot/D3Z3Z3|||http://purl.uniprot.org/uniprot/P54285 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel beta subunit family.|||Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1C) and the ancillary subunits CACNB3 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio. Interacts with CACNA2D4. Interacts with FASLG (By similarity). Interacts with CBARP; prevents the interaction of CACNB3 with the alpha subunit CACNA1C thereby negatively regulating the activity of the corresponding calcium channel (PubMed:24751537).|||Cytoplasm|||Detected in the inner plexiform layer in the retina (at protein level).|||Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:24751537). Increases CACNA1B peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity). Increases CACNA1C peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity). http://togogenome.org/gene/10090:ND3 ^@ http://purl.uniprot.org/uniprot/P03899|||http://purl.uniprot.org/uniprot/Q7GIP5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 3 family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Interacts with TMEM186. Interacts with TMEM242 (By similarity).|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Interacts with TMEM186. Interacts with TMEM242.|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity of complex I.|||Mitochondrion inner membrane|||Mitochondrion membrane http://togogenome.org/gene/10090:Bri3bp ^@ http://purl.uniprot.org/uniprot/Q8BXV2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with LETMD1. Interacts with BRI3. Interacts with BRI3; the interaction is weak (By similarity). Interacts with TMEM238L (By similarity).|||Involved in tumorigenesis and may function by stabilizing p53/TP53.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Gripap1 ^@ http://purl.uniprot.org/uniprot/Q8VD04 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early endosome membrane|||Expressed in the central nervous system, including cortex, cerebellum, midbrain and spinal cord, and in primary cultured hippocampal neurons but absent in non-neuronal tissues and cell types with the exception of neuroendocrine insulinoma cells.|||Functions as a scaffold protein to facilitate MAP3K1/MEKK1-mediated activation of the JNK1 kinase by phosphorylation, possibly by bringing MAP3K1/MEKK1 and JNK1 in close proximity (By similarity).|||Interacts with GRIP1, GRIP2 and AMPA receptors. Interacts (via C-terminus) with MAPK8/JNK1 and MAP3K1/MEKK1; the interaction promotes MAP3K1-mediated phosphorylation of MAPK8. Interacts (via N-terminus) with RAB4A (in GTP-bound form) (By similarity). Interacts (via C-terminus) with STX12 (PubMed:20098723).|||Proteolytically cleaved by caspase-3. A minor C-terminal proteolytic fragment of 30 kDa is produced. Proteolytic cleavage is required for JNK signaling activation.|||Recycling endosome membrane|||Regulates the endosomal recycling back to the neuronal plasma membrane, possibly by connecting early and late recycling endosomal domains and promoting segregation of recycling endosomes from early endosomal membranes. Involved in the localization of recycling endosomes to dendritic spines, thereby playing a role in the maintenance of dendritic spine morphology. Required for the activity-induced AMPA receptor recycling to dendrite membranes and for long-term potentiation and synaptic plasticity (By similarity).|||Synapse|||axon|||dendrite http://togogenome.org/gene/10090:Zfp580 ^@ http://purl.uniprot.org/uniprot/Q9DB38 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with SMAD2.|||Involved in the regulation of endothelial cell proliferation and migration. Mediates H(2)O(2)-induced leukocyte chemotaxis by elevating interleukin-8 production and may play a role in inflammation. May be involved in transcriptional regulation (By similarity).|||Nucleus http://togogenome.org/gene/10090:Upf3a ^@ http://purl.uniprot.org/uniprot/Q3ULJ3 ^@ Similarity ^@ Belongs to the RENT3 family. http://togogenome.org/gene/10090:Tmem59 ^@ http://purl.uniprot.org/uniprot/Q9QY73 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a regulator of autophagy in response to S.aureus infection by promoting activation of LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C). Acts by interacting with ATG16L1, leading to promote a functional complex between LC3 and ATG16L1 and promoting LC3 lipidation and subsequent activation of autophagy. Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of several proteins such as APP, BACE1, SEAP or PRNP. Inhibits APP transport to the cell surface and further shedding.|||Belongs to the TMEM59 family.|||Cell membrane|||Golgi apparatus membrane|||Interacts with ATG16L1 (via WD repeats).|||Late endosome membrane|||Lysosome membrane|||N-glycosylated.|||The ATG16L1-binding motif mediates interaction with ATG16L1 and promotes autophagy. http://togogenome.org/gene/10090:Sptb ^@ http://purl.uniprot.org/uniprot/Q3UGX2 ^@ Similarity ^@ Belongs to the spectrin family. http://togogenome.org/gene/10090:Tead1 ^@ http://purl.uniprot.org/uniprot/Q3UFP5|||http://purl.uniprot.org/uniprot/Q3USK5|||http://purl.uniprot.org/uniprot/Q6PAQ8|||http://purl.uniprot.org/uniprot/Q80W05 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ambp ^@ http://purl.uniprot.org/uniprot/Q07456 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3-hydroxykynurenine, an oxidized tryptophan metabolite that is common in biological fluids, reacts with Cys-53, Lys-111, Lys-137, and Lys-149 to form heterogeneous polycyclic chromophores including hydroxanthommatin. The reaction by alpha-1-microglobulin is autocatalytic; the human protein forms chromophore even when expressed in insect and bacterial cells. The chromophore can react with accessible cysteines forming non-reducible thioether cross-links with other molecules of alpha-1-microglobulin or with other proteins such as Ig alpha-1 chain C region 'Cys-352'.|||Antioxidant and tissue repair protein with reductase, heme-binding and radical-scavenging activities. Removes and protects against harmful oxidants and repairs macromolecules in intravascular and extravascular spaces and in intracellular compartments. Intravascularly, plays a regulatory role in red cell homeostasis by preventing heme- and reactive oxygen species-induced cell damage. Binds and degrades free heme to protect fetal and adult red blood cells from hemolysis. Reduces extracellular methemoglobin, a Fe3+ (ferric) form of hemoglobin that cannot bind oxygen, back to the Fe2+ (ferrous) form deoxyhemoglobin, which has oxygen-carrying potential. Upon acute inflammation, inhibits oxidation of low-density lipoprotein particles by MPO and limits vascular damage. Extravascularly, protects from oxidation products formed on extracellular matrix structures and cell membranes. Catalyzes the reduction of carbonyl groups on oxidized collagen fibers and preserves cellular and extracellular matrix ultrastructures. Importantly, counteracts the oxidative damage at blood-placenta interface, preventing leakage of free fetal hemoglobin into the maternal circulation. Intracellularly, has a role in maintaining mitochondrial redox homeostasis. Bound to complex I of the respiratory chain of mitochondria, may scavenge free radicals and preserve mitochondrial ATP synthesis. Protects renal tubule epithelial cells from heme-induced oxidative damage to mitochondria. Reduces cytochrome c from Fe3+ (ferric) to the Fe2+ (ferrous) state through formation of superoxide anion radicals in the presence of ascorbate or NADH/NADPH electron donor cofactors, ascorbate being the preferred cofactor (By similarity). Has a chaperone role in facilitating the correct folding of bikunin in the endoplasmic reticulum compartment (PubMed:32092411).|||Cell membrane|||Endoplasmic reticulum|||Expressed by the liver and secreted in plasma (at protein level).|||Heavy chains are interlinked with bikunin via a chondroitin 4-sulfate bridge to the C-terminal aspartate.|||I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (HC) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of ITIH1/HC1, ITIH2/HC2 and bikunin, and pre-alpha-inhibitor (P-alpha-I) of ITIH3/HC3 and bikunin. Interacts with TNFAIP6 (via Link domain).|||In the N-terminal section; belongs to the calycin superfamily. Lipocalin family.|||Kunitz-type serine protease inhibitor and structural component of extracellular matrix with a role in extracellular space remodeling and cell adhesion. Among others, has antiprotease activity toward kallikrein, a protease involved in airway inflammation; inhibits GZMK/granzyme, a granule-stored serine protease involved in NK and T cell cytotoxic responses; and inhibits PLG/plasmin, a protease required for activation of matrix metalloproteinases. As part of I-alpha-I complex, provides for the heavy chains to be transferred from I-alpha-I complex to hyaluronan in the presence of TNFAIP6, in a dynamic process that releases free bikunin and remodels extracellular matrix proteoglycan structures. Free bikunin, but not its heavy chain-bound form, acts as potent protease inhibitor in airway secretions (By similarity). Part of hyaluronan-rich extracellular matrix that surrounds oocyte during cumulus oophorus expansion, an indispensable process for proper ovulation (PubMed:11145954, PubMed:11243855). Also inhibits calcium oxalate crystallization (By similarity).|||Kunitz-type serine protease inhibitor. Has high catalytic efficiency for F10/blood coagulation factor Xa and may act as an anticoagulant by inhibiting prothrombin activation. Inhibits trypsin and mast cell CMA1/chymase and tryptase proteases.|||Mice are born at the expected Mendelian rate. Mutant female mice show severe infertility due to impaired cumulus oophorus expansion upon gonadotropin surge.|||Mitochondrion inner membrane|||Monomer. Also occurs as a complex with tryptase in mast cells.|||Monomer. Homodimer. In plasma, it occurs as a monomer or dimer and in covalently-linked complexes with immunoglobulin A (IgA), ALB/albumin and F2/prothrombin. Chromophore-bound alpha-1-microglobulin interacts with the constant region of immunoglobulin A. Chromophore-bound alpha-1-microglobulin interacts with ALB with molar ratio 2:1 and 1:1; this interaction does not prevent fatty acid binding to ALB. Interacts with F2/prothrombin (via N-terminus) with molar ratio 2:1 and 1:1; this interaction does not prevent the activation of prothrombin to thrombin. Interacts with NDUFAB1, a subunit of mitochondrial complex I (By similarity). Interacts with FN1 (By similarity).|||Mutant mice has normal litter size. At 12 months of age they show significant increase in body weight, which is partly due to fat accumulation in the liver with a subsequent increase in liver mass (PubMed:32092411). They display an abnormal red blood cell morphology, similar to macrocytic anemia characterized by fewer, larger and heterogeneous red cells (PubMed:32092412).|||Nucleus membrane|||Proteolytically cleaved by PRSS3 at Kunitz domain 2.|||Secreted|||The Kunitz domains 1 and 2 serve as protease inhibitor domains.|||The precursor is proteolytically processed into separately functioning proteins.|||cytosol|||extracellular matrix http://togogenome.org/gene/10090:F3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J088|||http://purl.uniprot.org/uniprot/P20352 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tissue factor family.|||Expression in the liver oscillates in a circadian manner.|||Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited proteolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.|||Interacts with HSPE; the interaction, inhibited by heparin, promotes the generation of activated factor X and activates coagulation in the presence of activated factor VII.|||Membrane http://togogenome.org/gene/10090:Farp1 ^@ http://purl.uniprot.org/uniprot/F8VPU2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in brain cortex, hippocampus, striatum, olfactory bulb, cerebellum and hindbrain (at protein level).|||Functions as guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity).|||Interacts with CADM1. Interacts with RAC1 (By similarity).|||Intramolecular interaction between the DH domain and the PH domains can stabilize the protein in an autoinhibited conformation.|||Synapse|||cytosol|||dendrite|||dendritic spine|||filopodium|||synaptosome http://togogenome.org/gene/10090:Spcs3 ^@ http://purl.uniprot.org/uniprot/Q6ZWQ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPCS3 family.|||Component of the signal peptidase complex paralog A (SPC-A) composed of a catalytic subunit SEC11A and three accessory subunits SPCS1, SPCS2 and SPCS3. Component of the signal peptidase complex paralog C (SPC-C) composed of a catalytic subunit SEC11C and three accessory subunits SPCS1, SPCS2 and SPCS3. Within the complex, interacts with SEC11A or SEC11C and SPCS1. The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids.|||Endoplasmic reticulum membrane|||Essential component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (By similarity). Essential for the SPC catalytic activity, possibly by stabilizing and positioning the active center of the complex close to the lumenal surface (By similarity). http://togogenome.org/gene/10090:Polr1c ^@ http://purl.uniprot.org/uniprot/P52432 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I) and RNA polymerase III (Pol III) complexes consisting of at least 13 and 17 subunits, respectively.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I and III which synthesize ribosomal RNA precursors and small RNAs, such as 5S rRNA and tRNAs, respectively. RPAC1 is part of the Pol core element with the central large cleft and probably a clamp element that moves to open and close the cleft (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or2t26 ^@ http://purl.uniprot.org/uniprot/Q8VGD7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpc5 ^@ http://purl.uniprot.org/uniprot/H3BLN8|||http://purl.uniprot.org/uniprot/Q8CAL5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glypican family.|||Cell membrane|||Cell surface proteoglycan that bears heparan sulfate.|||Cell surface proteoglycan.|||extracellular space http://togogenome.org/gene/10090:Crnkl1 ^@ http://purl.uniprot.org/uniprot/P63154 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the crooked-neck family.|||Identified in the spliceosome C complex. Present in a spliceosome complex assembled in vitro containing CRNKL1, HPRP8BP and SNRPB2 (By similarity). Component of the minor spliceosome, which splices U12-type introns (By similarity). Interacts with PPIL2 (via the PPIase cyclophilin-type domain); they may form a trimeric complex with HSP90 (PubMed:15189447).|||Involved in pre-mRNA splicing process. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Setd2 ^@ http://purl.uniprot.org/uniprot/E9Q5F9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.|||Chromosome|||Embryonic lethality at 10.5-11.5 dpc. Embryos show severe vascular defects in embryo, yolk sac and placenta. Capillaries are abnormally dilated in embryos and yolk sacs and cannot be remodeled into large blood vessels or intricate networks. The embryonic vessels fail to invade the labyrinthine layer of placenta, which impair the embryonic-maternal vascular connection. Defects are not caused by the extraembryonic tissues. Impaired H3K36me3, but not H3K36me2 or H3K36me1.|||Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:18157086, PubMed:20133625). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (By similarity). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (PubMed:18157086, PubMed:20133625). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (By similarity). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (By similarity). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (By similarity). Acts as a tumor suppressor (By similarity). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (By similarity). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (By similarity). Required during angiogenesis (PubMed:20133625). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (PubMed:25242323). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (By similarity).|||May be automethylated.|||Nucleus|||Specifically inhibited by sinefungin derivatives.|||Specifically interacts with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A): binds to CTD heptad repeats doubly phosphorylated on 'Ser-2' and 'Ser-5' of each heptad. Interacts with HTT. Interacts with IWS1. Interacts with p53/TP53; leading to regulate p53/TP53 target genes. Component of a complex with HNRNPL. Interacts with TUBA1A; the interaction is independent on alpha-tubulin acetylation on 'Lys-40'.|||The low charge region mediates the transcriptional activation activity. http://togogenome.org/gene/10090:Setd6 ^@ http://purl.uniprot.org/uniprot/Q9CWY3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Automethylated.|||Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SETD6 subfamily.|||Monomer, homodimer and homotrimer; these structures are stabilized in the presence of S-adenosyl-L-methionine (SAM).|||Nucleus|||Protein-lysine N-methyltransferase. Monomethylates 'Lys-310' of the RELA subunit of NF-kappa-B complex, leading to down-regulation of NF-kappa-B transcription factor activity. Monomethylates 'Lys-8' of H2AZ (H2AZK8me1) (By similarity). Required for the maintenance of embryonic stem cell self-renewal (PubMed:23324626). Methylates PAK4. http://togogenome.org/gene/10090:Pla1a ^@ http://purl.uniprot.org/uniprot/Q8VI78 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Hydrolyzes the ester bond of the acyl group attached at the sn-1 position of phosphatidylserines (phospholipase A1 activity) and 1-acyl-2-lysophosphatidylserines (lysophospholipase activity) in the pathway of phosphatidylserines acyl chain remodeling (By similarity). Cleaves phosphatidylserines exposed on the outer leaflet of the plasma membrane of apoptotic cells producing 2-acyl-1-lysophosphatidylserines, which in turn enhance mast cell activation and histamine production. Has no activity toward other glycerophospholipids including phosphatidylcholines, phosphatidylethanolamines, phosphatidic acids or phosphatidylinositols, or glycerolipids such as triolein (By similarity).|||Secreted http://togogenome.org/gene/10090:Ppme1 ^@ http://purl.uniprot.org/uniprot/Q8BVQ5 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily.|||Binds PPP2CA and PPP2CB.|||Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme (By similarity).|||Phosphorylated by SIK1 following increases in intracellular sodium, leading to dissociation from the protein phosphatase 2A (PP2A) complex and subsequent dephosphorylation of sodium/potassium-transporting ATPase ATP1A1.|||Ubiquitous. Highly expressed in testis and brain. http://togogenome.org/gene/10090:Fam161a ^@ http://purl.uniprot.org/uniprot/B1AVK0|||http://purl.uniprot.org/uniprot/Q8QZV6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM161 family.|||Expressed at low levels from 12.5 to 16.5 dpc in the retinal progenitor cells of the optic cup, as well as in the posterior compartment of the lens. Expression drops in the retina at birth. At P5, highly expressed in the postmigratory photoreceptor precursors at the apical side of the outer nuclear layer. At P10, present in the outer nuclear layer and in the inner segments of photoreceptors and in the outer plexiform layer (at protein level). In adult animals, at P30, reaches a well-defined localization in the inner segment of photoreceptors, as well as in the outer plexiform layer (at protein level). Completely absent from the outer segment of photoreceptors (at protein level).|||Expressed in the retina.|||Interacts (via central region) with CFAP418 (via N-terminus); the interaction is direct (By similarity). Interacts (via C-terminus) with microtubules (By similarity). Interacts with LCA5 (By similarity). Interacts with CEP290 (By similarity). Interacts with SDCCAG8 (By similarity). Interacts with FAM161B (By similarity). Interacts with POC1B (By similarity). Interacts with CEP78 (By similarity).|||Involved in ciliogenesis.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Nlrp4a ^@ http://purl.uniprot.org/uniprot/B2RUQ7|||http://purl.uniprot.org/uniprot/Q8BU40 ^@ Function|||Similarity ^@ Belongs to the NLRP family.|||May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. http://togogenome.org/gene/10090:Vmn1r157 ^@ http://purl.uniprot.org/uniprot/E9Q069 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cpt2 ^@ http://purl.uniprot.org/uniprot/P52825|||http://purl.uniprot.org/uniprot/Q3UN55 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the carnitine/choline acetyltransferase family.|||Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites. Reconverts acylcarnitines back into the respective acyl-CoA esters that can then undergo beta-oxidation, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Tlr12 ^@ http://purl.uniprot.org/uniprot/A2RRZ9|||http://purl.uniprot.org/uniprot/Q6QNU9 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Toll-like receptor family.|||Binds MYD88 via their respective TIR domains.|||Has increased susceptibility to the uropathogenic E.coli strain 8NU. Following infection, kidneys show a significantly increased bacterial load and increased inflammatory response, whereas bladder shows a similar response to wild type.|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||Macrophages, liver, kidney and bladder epithelial cells.|||Membrane|||Participates in the innate immune response to microbial agents. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Plays a role in preventing infection of internal organs of the urogenital system.|||There is some confusion regarding the nomenclature of this gene. In the literature, Tlr12 is frequently referred to as Tlr11 and vice-versa. http://togogenome.org/gene/10090:Or4n4b ^@ http://purl.uniprot.org/uniprot/Q14AK5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gbp5 ^@ http://purl.uniprot.org/uniprot/Q8BMN7|||http://purl.uniprot.org/uniprot/Q8CFB4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Golgi apparatus membrane|||Homodimer; homodimerizes upon GTP-binding, forming a close face-to-face dimer. Heterodimer with other family members, including GBP1, GBP2, GBP3 and GBP4. May also form tetramers (dimer of dimers) in the presence of GTP. Interacts with NLRP3, possibly in its tetrameric form, and promotes PYCARD/ASC polymerization.|||Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:22461501, PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716, PubMed:27693356, PubMed:30589883). Hydrolyzes GTP, but in contrast to other family members, does not produce GMP (By similarity). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis, such as Gm12250/Irgb10: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716, PubMed:27693356, PubMed:30589883). As an activator of NLRP3 inflammasome assembly: promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity by inhibiting FURIN-mediated maturation of viral envelope proteins (By similarity).|||Isoprenylation is required for proper subcellular location.|||Low expression, if any, in many tissues in the absence of stimulation.|||Mutant mice exhibit impaired host defense and NLRP3-dependent inflammatory responses. During LPS-induced sepsis, knockout animals show 60 to 75% reduction in IL1B and IL-18 serum levels compared to wild-type mice. Orogastric challenge with Listeria monocytogenes leads to higher bacterial burdens, discernible weight loss, and 50 to 80% fewer leukocytes expressing active CASP1 in mesenteric lymph nodes compared to wild-type counterparts.|||Strongly up-regulated by IFNG and, at lower levels, by LPS. The LPS-induced increase is attenuated in the presence of dexamethasone (PubMed:12396730, PubMed:18025219). Up-regulated by TNF in certain strains (PubMed:12396730). Up-regulation by a combination of IFNG and TNF is synergistic, even in strains that do not respond to TNF alone (PubMed:12396730). By IRF1 in response to bacterial infection (PubMed:25774715). http://togogenome.org/gene/10090:Elf5 ^@ http://purl.uniprot.org/uniprot/Q3ULZ4|||http://purl.uniprot.org/uniprot/Q3V1F7|||http://purl.uniprot.org/uniprot/Q8VDK3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ETS family.|||Expressed in lung, kidney, stomach, brain, ovaries, tongue, bladder and mammary glands.|||In the neonatal stage, and during embryogenesis on days 16, 17 and 19, an expression pattern similar to the adult was observed. In addition at stage 16, expression was detected in small intestine.|||Nucleus|||The PNT domain acts as a transcriptional activator.|||Transcriptionally activator that may play a role in regulating the later stages of keratinocytes terminal differentiation (By similarity). Binds to DNA sequences containing the consensus nucleotide core sequence GGA[AT]. Transcriptionally activates the TK promoter. http://togogenome.org/gene/10090:Rnf2 ^@ http://purl.uniprot.org/uniprot/Q9CQJ4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of chromatin-associated Polycomb (PcG) complexes (PubMed:22325148). Component of a number of PRC1-like complexes; these complexes contain either the polycomb group ring finger protein PCGF1, or PCGF2, or PCGF3, or BMI1, or PCGF5, or PCGF6 (PubMed:28596365, PubMed:16710298). Distinct PRC1-like complexes are composed of a RING1 subunit (RING1B or RING1A), one of the six PCGF proteins (PCGF1, PCGF2, PCGF3, BMI1, PCGF5 or PCGF6), one PHC protein (PHC1, PHC2 or PHC3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8) (Probable). Part of a complex that contains RNF2, UB2D3 and BMI1; within that complex RNF2 and BMI1 form a tight heterodimer, where UB2D3 interacts only with RNF2. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A (By similarity). Part of a complex that contains PCGF5, RNF2 and UBE2D3. Part of a complex that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP (By similarity). Interacts with CBX6 and CBX8 (By similarity). Interacts with PHC1, PCGF2, RYBP, CBX7, CBX4, CBX2, RNF1/RING1, BMI1 and PHC2 (PubMed:12183370, PubMed:16024804, PubMed:16710298, PubMed:19170609, PubMed:9312051, PubMed:10369680, PubMed:22325148, PubMed:22226355). Interaction with RYBP and CBX7 is mutually exclusive; both compete for the same binding site on RNF2 (PubMed:22325148). Component of repressive BCOR complex containing a Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RING1 (By similarity). Interacts with CBX2 and PHC1 (PubMed:22226355). Interacts with CHTOP (PubMed:22872859). Interacts with AURKB (PubMed:24034696). Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RNF1/RING1, RNF2/RING2, MBLR, L3MBTL2 and YAF2 (By similarity). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with RYBP, HIP2 and TFCP2 (By similarity). Interacts with NUPR1 (By similarity).|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation (PubMed:15525528, PubMed:22325148, PubMed:28596365). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals (PubMed:15525528, PubMed:28596365). May be involved in the initiation of both imprinted and random X inactivation (PubMed:15525528). Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:22325148, PubMed:16710298). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:15525528, PubMed:22325148, PubMed:16710298). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:16710298). Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (PubMed:15525528, PubMed:16710298). Plays a role in the transcriptional repression of genes that are required for pluripotency in embryonic stem cells, thereby contributing to differentiation of the ectodermal and endodermal germ layers (PubMed:22226355). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes (PubMed:24034696). Also acts as a negative regulator of autophagy by mediating ubiquitination of AMBRA1, leading to its subsequent degradation (PubMed:24980959).|||Expressed in embryonic stem cells.|||Monoubiquitinated, by auto-ubiquitination (PubMed:16710298). Polyubiquitinated in the presence of UBE2D3 (in vitro) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Txlnb ^@ http://purl.uniprot.org/uniprot/Q8VBT1 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the taxilin family.|||Binds to the C-terminal coiled coil region of syntaxin family members STX1A, STX3A and STX4A. Has a preference for STX1A (By similarity).|||Promotes motor nerve regeneration. May be involved in intracellular vesicle traffic (By similarity).|||Specifically expressed in skeletal muscle. http://togogenome.org/gene/10090:Prmt8 ^@ http://purl.uniprot.org/uniprot/Q6PAK3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT8 subfamily.|||Brain-specific. Only expressed in neurons, especially in the somatosensory and limbic systems, and a part of motor system. Highly expressed in all of the regions related to general somatosensory system. Expressed in most of the relay nuclei intervening the special somatosensory system, such as the auditory, visual and vestibular systems. Also present in forebrain limbic areas and thalamic nuclei relevant to limbic areas and in areas related to the motor system, such as the caudate putamen, Purkinje cells, inferior olivary nucleus and cerebellar nuclei.|||Cell membrane|||Homodimer. Tetramer; individual homodimers associates to form a homotetramer. Homooctamer; individual homodimers associates to form a homooctamer and homooligomerization is required for proper localization to the cell membrane. Heterodimer with PRMT1; heterodimerization may recruit PRMT1 activity to the plasma membrane. Interacts with PRMT2 (via the SH3 domain). Interacts with FYN (via the SH3 domain). Interacts with EWS; independently of EWS methylation status.|||S-adenosyl-L-methionine-dependent and membrane-associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA) in proteins such as NIFK, myelin basic protein, histone H4, H2A and H2A/H2B dimer. Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS.|||The N-terminal region (1-60) inhibits the arginine N-methyltransferase activity.|||The SH3-binding motifs mediate the interaction with SH3 domain-containing proteins such as PRMT2 and FYN, possibly leading to displace the N-terminal domain and activate the protein. http://togogenome.org/gene/10090:Pak4 ^@ http://purl.uniprot.org/uniprot/Q8BTW9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated on serine residues when activated by CDC42/p21 (By similarity). Phosphorylated on tyrosine residues upon stimulation of FGFR2 (PubMed:12529371). Methylated by SETD6.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Inhibited by INKA1; which inhibits the serine/threonine-protein kinase activity by binding PAK4 in a substrate-like manner.|||Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and weakly with RAC1 (By similarity). Interacts with FGFR2 and GRB2 (PubMed:12529371). Interacts with INKA1. Interacts with SH3RF2 (By similarity).|||Mice die at embryonic day 11.5 probably due to a defect in the fetal heart. They show strong defects in neuronal development and axonal outgrowth. Spinal cord motor neurons and interneurons failed to differentiate and migrate to their proper position. Nervous system-specific conditional PAK4 deletion mice display growth retardation and die prematurely.|||Polyubiquitinated, leading to its proteasomal degradation.|||Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. http://togogenome.org/gene/10090:Sdc1 ^@ http://purl.uniprot.org/uniprot/P18828|||http://purl.uniprot.org/uniprot/Q3V1F2 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syndecan proteoglycan family.|||Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix (PubMed:8163535). Regulates exosome biogenesis in concert with SDCBP and PDCD6IP (By similarity). Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (PubMed:8898217).|||Cell surface proteoglycan.|||Expressed in the dental mesenchyme at 13.5 dpc (at protein level).|||Interacts with CDCP1 (By similarity). Interacts (via C-terminus) with TIAM1 (via PDZ domain) (PubMed:20361982). Interacts with MDK (By similarity).|||Major isoform.|||Membrane|||Minor isoform.|||Secreted|||Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3.|||extracellular exosome http://togogenome.org/gene/10090:Pkd2l1 ^@ http://purl.uniprot.org/uniprot/A2A259 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the polycystin family.|||Cell membrane|||Cytoplasmic vesicle|||Detected in kidney, testis and brain, (PubMed:25820328). Expressed in all 4 taste areas in taste buds. Detected in the taste pore region of circumvallate papillae, foliate papillae, fungiform papillae and palate (PubMed:16891422, PubMed:16929298, PubMed:20538909, PubMed:21625513). Expressed in cells distinct from those mediating sweet, umami and bitter taste (at protein level) (PubMed:16891422). Expressed in type III taste cells (at protein level) (PubMed:18156604). Ubiquitous (PubMed:15548533). Detected in circumvallate, foliate, fungiform and palate taste buds, in cells distinct from those mediating sweet, umami and bitter taste (PubMed:16929298, PubMed:21625513). Detected in taste tissues and testis (PubMed:16891422).|||Homotetramer (PubMed:25820328, PubMed:29567962). Heterotetramer with either PKD1L1, PKD1L3 or PKD1; the heterotetrameric complex probably contains 3 PKD1L2 chains plus one chain from another family member (PubMed:16891422, PubMed:15548533, PubMed:25820328, PubMed:29567962). Interacts with PKD1L1, forming a ciliary calcium channel (PubMed:24336289). Interacts with PKD1L3, forming a cation channel that is activated by low extracellular pH (PubMed:16891422, PubMed:18535624, PubMed:19464260, PubMed:20538909, PubMed:20406802, PubMed:22420714, PubMed:25820328, PubMed:29567962). Interacts with PKD1 (PubMed:15548533). Interacts with RACK1; inhibits the channel activity possibly by impairing localization to the cell membrane (By similarity).|||Interaction of the cytoplasmic N- and C-terminal domains is important for channel activity.|||Intestinal malrotation in 50% of animals, while other organs do not show major organ laterality defects. Intestinal malformations are associated with SHH pathway defects during early development (PubMed:24336288). Partial reduction of chorda tympani nerve response to sour stimuli, without affecting sweet, salty, bitter, and umami perception (PubMed:21625513).|||Palmitoylation is important for expression at the cell membrane and for channel activity.|||Pkd1l3 and Pkd2l1 have been defined as sour taste receptor in gustatory cells based on a number of indirect evidences: Pkd2l1 is expressed in a subset of taste receptor cells distinct from those responsible for sweet, bitter and unami taste and genetic elimination of cells expressing Pkd2l1 reduces gustatory nerve responses to sour taste stimuli (PubMed:16891422, PubMed:16929298). However, a number of experiments have recently shown that the sour taste receptor activity is probably indirect: mice lacking Pkd2l1 only show partial defects in sour taste perception (PubMed:21625513). Moreover, the PKD1L3-PKD2L1 heteromer, when expressed in cells does not respond to acid stimuli used to evoke proton currents in taste cells (PubMed:21098668).|||Pore-forming subunit of a heteromeric, non-selective cation channel that is permeable to Ca(2+) (PubMed:16891422, PubMed:15548533, PubMed:19464260, PubMed:20538909, PubMed:21185261, PubMed:22420714, PubMed:25820328, PubMed:28904867, PubMed:29567962). Pore-forming subunit of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, but does not affect cytoplasmic calcium concentration (PubMed:24336288, PubMed:24336289). The channel formed by PKD1L2 and PKD1L1 in primary cilia regulates sonic hedgehog/SHH signaling and GLI2 transcription (PubMed:24336288). Pore-forming subunit of a channel formed by PKD1L2 and PKD1L3 that contributes to sour taste perception in gustatory cells (PubMed:16891422, PubMed:16929298, PubMed:20406802, PubMed:21098668, PubMed:21625513). The heteromeric channel formed by PKD1L2 and PKD1L3 is activated by low pH, but opens only when the extracellular pH rises again (PubMed:18535624, PubMed:19464260, PubMed:20538909, PubMed:20406802, PubMed:22420714, PubMed:28904867, PubMed:29567962). May play a role in the perception of carbonation taste (PubMed:19833970). May play a role in the sensory perception of water, via a mechanism that activates the channel in response to dilution of salivary bicarbonate and changes in salivary pH (PubMed:28553944).|||The EF-hand domain probably mediates calcium-binding. It is not required for channel activation.|||The active channel complex is an obligate tetramer (PubMed:29567962). In contrast, the isolated cytoplasmic C-terminal domain forms homotrimers in vitro (PubMed:25820328). Likewise, photobleaching experiments suggest formation of homotrimers in the membrane (By similarity).|||The ion channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application (PubMed:18535624, PubMed:19464260, PubMed:20406802, PubMed:22420714, PubMed:28904867, PubMed:29567962). Responses to acid stimulus are inhibited by capsaicin (PubMed:22420714).|||cilium membrane http://togogenome.org/gene/10090:Ints1 ^@ http://purl.uniprot.org/uniprot/Q6P4S8 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12 (By similarity). Interacts with ESRRB, ESRRB is probably not a core component of the multiprotein complex Integrator and this association is a bridge for the interaction with the multiprotein complex Integrator; attracts the transcriptional machinery (PubMed:26206133).|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Could be due to alternative splicing but with non canonical splice junction.|||Nucleus membrane http://togogenome.org/gene/10090:Srp54b ^@ http://purl.uniprot.org/uniprot/P14576 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTP-binding SRP family. SRP54 subfamily.|||Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9 (By similarity). Interacts with RNPS1 (By similarity). Interacts with the SRP receptor subunit SRPRA (By similarity).|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (By similarity). As part of the SRP complex, associates with the SRP receptor (SR) component SRPRA to target secretory proteins to the endoplasmic reticulum membrane (By similarity). Binds to the signal sequence of presecretory proteins when they emerge from the ribosomes (By similarity). Displays basal GTPase activity, and stimulates reciprocal GTPase activation of the SR subunit SRPRA (By similarity). Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SR subunit SRPRA (By similarity). SR compaction and GTPase mediated rearrangement of SR drive SRP-mediated cotranslational protein translocation into the ER (By similarity). Requires the presence of SRP9/SRP14 and/or SRP19 to stably interact with RNA (By similarity). Plays a role in proliferation and differentiation of granulocytic cells, neutrophils migration capacity and exocrine pancreas development (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Nucleus speckle|||The M domain binds the 7SL RNA in presence of SRP19 and binds the signal sequence of presecretory proteins.|||The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA (By similarity). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (By similarity). SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (By similarity). http://togogenome.org/gene/10090:Prrt1 ^@ http://purl.uniprot.org/uniprot/A2CG20|||http://purl.uniprot.org/uniprot/O35449 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||Cell membrane|||Component of the outer core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.|||Decreased Gria1/GluA1 and Gria2/GluA2 density at extrasynaptic sites and increased density of Gria1 at synapses (PubMed:29490264). Reduced cell surface expression of Gria1 and Gria2 (PubMed:31216424). Reduced phosphorylation of Gria1 'Ser-863' and increased phosphorylation of Gria1 'Ser-849' (PubMed:31216424). Reduced synaptic transmission in immature hippocampal neurons (PubMed:29490264). No change in basal synaptic transmission in mature hippocampal neurons (PubMed:31216424). Shown to impair tetanus-induced long-term potentiation (LTP) in 8-12 week old mice in one study (PubMed:29490264). Another study shows no effect on LTP in young mature mice at postnatal days 24-36 (PubMed:31216424). Severely impaired long-term depression (PubMed:31216424). Deficiency in cognitive learning and memory tasks (PubMed:29490264).|||Expressed in the brain (at protein level) (PubMed:22632720). In brain, expressed throughout the hippocampus with weak expression in the olfactory bulb and neocortex (at protein level) (PubMed:29490264).|||Required to maintain a pool of extrasynaptic AMPA-regulated glutamate receptors (AMPAR) which is necessary for synapse development and function (PubMed:29490264). Regulates AMPAR function and synaptic transmission during development but is dispensable at mature hippocampal synapses (PubMed:29490264, PubMed:31216424). Plays a role in regulating basal phosphorylation levels of glutamate receptor GRIA1 and promotes GRIA1 and GRIA2 cell surface expression (PubMed:31216424).|||Synapse http://togogenome.org/gene/10090:Nkpd1 ^@ http://purl.uniprot.org/uniprot/Q0VF94 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ppp1r14bl ^@ http://purl.uniprot.org/uniprot/Q14BX6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PP1 inhibitor family.|||Inhibitor of PPP1CA.|||Membrane http://togogenome.org/gene/10090:Tmx1 ^@ http://purl.uniprot.org/uniprot/Q8VBT0 ^@ Function|||Subcellular Location Annotation ^@ Endoplasmic reticulum membrane|||May participate in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions.|||Membrane http://togogenome.org/gene/10090:Atp5g3 ^@ http://purl.uniprot.org/uniprot/P56384|||http://purl.uniprot.org/uniprot/Q14BC2 ^@ Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase C chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Interacts with TMEM70 and TMEM242 (By similarity).|||Membrane|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. A homomeric c-ring of probably 10 subunits is part of the complex rotary element.|||Mitochondrion membrane|||There are three genes which encode the mitochondrial ATP synthase proteolipid and they specify precursors with different import sequences but identical mature proteins.|||This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).|||Trimethylated by ATPSCKMT at Lys-109. Methylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration. http://togogenome.org/gene/10090:Ccdc85b ^@ http://purl.uniprot.org/uniprot/Q6PDY0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC85 family.|||Expressed in white and brown adipose tissue.|||Functions as a transcriptional repressor. May inhibit the activity of CTNNB1 in a TP53-dependent manner and thus regulate cell growth. May function in adipocyte differentiation, negatively regulating mitotic clonal expansion (PubMed:15644333, PubMed:22666460). Plays a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family (By similarity).|||Interacts with CEBPB (PubMed:15644333). May interact with CEBPD (Probable). Interacts with EURL (PubMed:27404227). Interacts with MCRS1 (By similarity). Interacts with TCF7L2; competes with CTNNB1 (By similarity). Interacts with ANKRD26 (By similarity). Interacts with the beta-catenin family proteins ARVCF, CTNND1, CTNND2 and PKP4 (By similarity).|||Nucleus|||adherens junction|||centrosome http://togogenome.org/gene/10090:Echdc3 ^@ http://purl.uniprot.org/uniprot/Q9D7J9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||May play a role in fatty acid biosynthesis and insulin sensitivity.|||Mitochondrion http://togogenome.org/gene/10090:Actr1b ^@ http://purl.uniprot.org/uniprot/Q8R5C5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the actin family. ARP1 subfamily.|||Component of a multi-subunit complex involved in microtubule based vesicle motility. It is associated with the centrosome (By similarity).|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Spink8 ^@ http://purl.uniprot.org/uniprot/Q09TK9 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in epydiymis, in the cauda, corpus and caput.|||Probable serine protease inhibitor.|||Secreted http://togogenome.org/gene/10090:Znrf4 ^@ http://purl.uniprot.org/uniprot/Q9DAH2 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in the testis from the postpubertal stage (23 days) onwards, with highest expression at 29 days.|||E3 ubiquitin-protein ligase that acts as a negative regulator of NOD2 signaling by mediating ubiquitination and degradation of RIPK2 (By similarity). Also catalyzes ubiquitination and proteasomal degradation of CANX within the endoplasmic reticulum (By similarity). Could have a role in spermatogenesis (PubMed:10191088).|||Endoplasmic reticulum membrane|||Expressed exclusively in spermatids (at protein level).|||Interacts with CANX.|||The RING-type zinc finger is involved in CANX ubiquitination and degradation, but is not required for interaction with CANX. http://togogenome.org/gene/10090:Otx1 ^@ http://purl.uniprot.org/uniprot/P80205|||http://purl.uniprot.org/uniprot/Q5SS54 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Brain: restricted regions of the developing rostral brain including the presumptive cerebral cortex and olfactory bulbs; expressed in the developing olfactory, auricolar and ocular systems, including the covering of the optic nerve.|||Embryo.|||Nucleus|||Probably plays a role in the development of the brain and the sense organs. Can bind to the BCD target sequence (BTS): 5'-TCTAATCCC-3'. http://togogenome.org/gene/10090:Rai14 ^@ http://purl.uniprot.org/uniprot/Q9EP71 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 days, expression is detected in branchial arch mesenchyme, forebrain, hindbrain, midbrain, and neural tube. At 12.5 days, is detected in the hindbrain, forebrain, lung, genital eminence, spinal ligaments around vertebrae and ribs, and around the cartilage of ribs and nasal sinuses. Also detected in frontonasal mass, mandibular arch, optic sulcus, spinal ganglia and hind limb bud. At 15.5 days, expression is detected in the ventricular layer of neurons subjacent to the neocortex, around the nasal sinuses, bronchioles of the lung, kidney, and around the vertebrae of the tail. Also seen in the olfactory bulb.|||Cell junction|||Highly expressed in testis, where it localizes to seminiferous tubules (at protein level) (PubMed:11042181, PubMed:16806700). Expressed in ganglion cell layer and in Muller cell fibers of the retina (at protein level) (PubMed:11042181, PubMed:16806700). In small intestine highly expressed at the apical and lateral borders of absorptive epithelia (at protein level) (PubMed:11168586). In liver highly expressed along the bile canaliculi (at protein level) (PubMed:11168586).|||Interacts with PALLD (By similarity). Associates with actin (PubMed:11168586). However, does not bind F-actin directly (PubMed:11168586).|||Nucleus|||Plays a role in actin regulation at the ectoplasmic specialization, a type of cell junction specific to testis. Important for establishment of sperm polarity and normal spermatid adhesion. May also promote integrity of Sertoli cell tight junctions at the blood-testis barrier.|||cell cortex|||cytoskeleton|||stress fiber http://togogenome.org/gene/10090:Tbc1d13 ^@ http://purl.uniprot.org/uniprot/Q8R3D1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a GTPase-activating protein for RAB35. Together with RAB35 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes.|||Cytoplasm|||Expressed in adipocytes.|||Interacts with RAB1A and RAB10; in a GTP-dependent manner.|||Membrane http://togogenome.org/gene/10090:Tmem201 ^@ http://purl.uniprot.org/uniprot/A2A8U2|||http://purl.uniprot.org/uniprot/Q3TXY3|||http://purl.uniprot.org/uniprot/Q8C397 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM201 family.|||Involved in nuclear movement during fibroblast polarization and migration (PubMed:22349700). May recruit Ran GTPase to the nuclear periphery (By similarity).|||Isoform 2 interacts with EMD (By similarity). Isoform 3 interacts with SUN2 and LMNA (PubMed:22349700). May bind to Ran GTPase; has a greater affinity for Ran-GTP over Ran-GDP (By similarity).|||May define a distinct membrane domain in the vicinity of the mitotic spindle. Involved in the organization of the nuclear envelope implicating EMD, SUN1 and A-type lamina.|||Membrane|||Nucleus inner membrane|||Proposed to be involved in actin-dependent nuclear movement; via SUN2 associates with transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow. http://togogenome.org/gene/10090:Fgf15 ^@ http://purl.uniprot.org/uniprot/O35622|||http://purl.uniprot.org/uniprot/Q790L8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Expressed in the developing brain.|||Interacts with MALRD1.|||Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression.|||Secreted http://togogenome.org/gene/10090:Acads ^@ http://purl.uniprot.org/uniprot/Q07417 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acyl-CoA dehydrogenase family.|||Binds 1 FAD per subunit.|||Homotetramer.|||Mitochondrion matrix|||Short-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats. The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA. Among the different mitochondrial acyl-CoA dehydrogenases, short-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 4 to 6 carbons long primary chains. http://togogenome.org/gene/10090:Ppic ^@ http://purl.uniprot.org/uniprot/P30412|||http://purl.uniprot.org/uniprot/Q3UC73 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cyclophilin-type PPIase family.|||Cytoplasm|||Inhibited by cyclosporin A (CsA).|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.|||Specifically expressed in kidney. http://togogenome.org/gene/10090:Lzts1 ^@ http://purl.uniprot.org/uniprot/P60853 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LZTS family.|||Binds EEF1G, TLK2 and CDK1.|||Cell membrane|||Cytoplasm|||Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as tumor suppressor (By similarity).|||Phosphorylated on serine residues. Hyperphosphorylated by the cAMP-dependent kinase PKA during cell-cycle progression (By similarity).|||Postsynaptic density|||Synapse|||dendritic spine http://togogenome.org/gene/10090:Catsperg1 ^@ http://purl.uniprot.org/uniprot/E9Q355 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CATSPERG family.|||Despite its name, it is unclear whether the protein is part of some Catsper complex: in contrast to Catsperg2, it has not been identified in the Catsper complex and its expression is not restricted to testis tissues.|||Membrane http://togogenome.org/gene/10090:Cyp2c39 ^@ http://purl.uniprot.org/uniprot/P56656 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that primarily catalyzes the epoxidation of 11,12 and 14,15 double bonds of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) forming 11,12- and 14,15-epoxyeicosatrienoic acids (11,12- and 14,15-EET) regioisomers. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Liver.|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Adamts12 ^@ http://purl.uniprot.org/uniprot/Q811B3 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Inhibited by alpha-2 macroglobulin.|||Interacts with COMP.|||Metalloprotease that plays a role in the degradation of COMP (By similarity). Cleaves also alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties (By similarity).|||Subjected to an intracellular maturation process yielding a 120 kDa N-terminal fragment containing the metalloproteinase, disintegrin, one TSP type-1 and the Cys-rich domains and a 83 kDa C-terminal fragment containing the spacer 2 and four TSP type-1 domains.|||The C-terminal four TSP1-like repeats are necessary and sufficient for binding COMP.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Otog ^@ http://purl.uniprot.org/uniprot/O55225 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the otogelin family.|||Expressed in the epithelial cells of the otic vesicle at 10 dpc. Expressed in non-sensory cells of the developing vestibule, in the transitory epithelium of the saccule, utricle and cristae ampullares, in epithelial cells of the roof of the saccule, but not the roof of the utricle nor the cristae ampullares at 13 dpc. Expressed in supporting cells of the vestibular maculae at 13 dpc onward birth. Expressed in non-sensory cells of the emerging cochlear duct at 12 dpc. Expressed in the pluristratified sensory epithelium as well as in the epithelium of the roof at 14 dpc. Expressed in the developing sensory epithelium (the spiral limbus, the greater epithelial ridge and the lesser epithelial ridge) of the cochlear duct, the interdental cells of the spiral limbus and in the columnar cells that form the greater epithelial ridge at 16 and 17 dpc. Expressed in the non-sensory pillar, Deiter's and Hensen's cells of the organ of Corti and Claudius cells at 19 dpc onward birth (at protein level).|||Expressed specifically in neuroepithelial supporting cells of the inner ear. Expressed in the cochlea between postnatal day P0 and P6 in pseudostratified cells of the greater epithelial ridge, in supporting cells of the neuroepithelium comprising Deiter's, Hensen's, pillar and Claudius cells, in epithelial cells of the Reissner's membrane, in a small set of cells comprising the spiral prominence. Expressed in the cochlea at P15 in interdental cells located underneath the limbal part of the tectorial membrane. Expressed in the vestibular apparatus at P0 in supporting cells of the saccular, utricular maculae and cristae ampullares, in the epithelial cells of the roof of the saccule but not in the roof of the utricle and cristae ampullares (at protein level). Expressed in the cochlea and vestibular organ of the inner ear.|||Glycoprotein specific to acellular membranes of the inner ear. May be required for the anchoring of the otoconial membranes and cupulae to the underlying neuroepithelia in the vestibule. May be involved in the organization and/or stabilization of the fibrillar network that compose the tectorial membrane in the cochlea. May play a role in mechanotransduction processes.|||Impaired vestibular and auditory functions.|||N-glycosylated. Not O-glycosylated.|||extracellular space http://togogenome.org/gene/10090:Vwa5a ^@ http://purl.uniprot.org/uniprot/Q99KC8 ^@ Function ^@ May play a role in tumorigenesis as a tumor suppressor. Altered expression of this protein and disruption of the molecular pathway it is involved in may contribute directly to or modify tumorigenesis (By similarity). http://togogenome.org/gene/10090:Fahd2a ^@ http://purl.uniprot.org/uniprot/A0A0R4J094|||http://purl.uniprot.org/uniprot/Q3TC72 ^@ Function|||Similarity ^@ Belongs to the FAH family.|||May have hydrolase activity. http://togogenome.org/gene/10090:Slc25a39 ^@ http://purl.uniprot.org/uniprot/Q14BQ5|||http://purl.uniprot.org/uniprot/Q9D8K8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant expression in bone marrow, spleen, testis and kidney.|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Embryonic lethality at dpc 13.5 (PubMed:34707288). Embryos are pale due to a severely anemic phenotype (PubMed:34707288). Conditional deletion in the erythroid lineage also leads to severe anemia, characterized by a complete absence of Ter119(+) cells, iron overload and increased apoptosis in fetal liver cells (PubMed:34707288). Cells lacking both Slc25a39 and Slc25a40 show defects in the activity and stability of proteins containing iron-sulfur clusters (PubMed:34707288).|||Highly express in primitive erythroblast that fill yorlk sac blood islands at early somite pair stages, and in fetal liver at 12.5 dpc.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mitochondrial transporter required for glutathione import into mitochondria (PubMed:34707288). Glutathione, which plays key roles in oxidative metabolism, is produced exclusively in the cytosol and is imported in many organelles (By similarity). Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters, as well as erythropoiesis (PubMed:34707288).|||Mitochondrial transporter required for glutathione import into mitochondria. Glutathione, which plays key roles in oxidative metabolism, is produced exclusively in the cytosol and is imported in many organelles. Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters, as well as erythropoiesis.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or8h10 ^@ http://purl.uniprot.org/uniprot/Q8VFM1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ss18 ^@ http://purl.uniprot.org/uniprot/Q62280|||http://purl.uniprot.org/uniprot/Q6P1I1|||http://purl.uniprot.org/uniprot/Q8BJJ6|||http://purl.uniprot.org/uniprot/Q8BKL1|||http://purl.uniprot.org/uniprot/Q8VHA8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to function synergistically with RBM14 as a transcriptional coactivator. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.|||Belongs to the SS18 family.|||Interacts with MLLT10 (By similarity). Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, the core BAF subunits, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058).|||Nucleus|||Ubiquitously expressed in early embryogenesis (12.5 days). In later stages (14.5 days), the expression is restricted to cartilage forming cells, to specific neuronal cells and some epithelial derived tissues. In adults, SSXT is expressed in heart, kidney, testis and also in muscle, brain and liver. In mature testis, expression is specifically observed in primary spermatocytes. http://togogenome.org/gene/10090:Adamtsl1 ^@ http://purl.uniprot.org/uniprot/Q8BLI0 ^@ Caution|||PTM|||Subcellular Location Annotation|||Subunit ^@ Although strongly similar to members of the ADAMTS family it lacks the metalloprotease and disintegrin-like domains which are typical of that family.|||Disulfide bonds are present.|||Glycosylated (By similarity). O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Monomer.|||extracellular matrix http://togogenome.org/gene/10090:Zg16 ^@ http://purl.uniprot.org/uniprot/Q8K0C5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the jacalin lectin family.|||Golgi apparatus lumen|||May play a role in protein trafficking. May act as a linker molecule between the submembranous matrix on the luminal side of zymogen granule membrane (ZGM) and aggregated secretory proteins during granule formation in the TGN (By similarity).|||Zymogen granule lumen|||extracellular matrix http://togogenome.org/gene/10090:Duxbl1 ^@ http://purl.uniprot.org/uniprot/Q7TNE6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Impdh1 ^@ http://purl.uniprot.org/uniprot/P50096 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IMPDH/GMPR family.|||Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.|||Cytoplasm|||Homotetramer.|||Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.|||Nucleus http://togogenome.org/gene/10090:Arl3 ^@ http://purl.uniprot.org/uniprot/Q543P7|||http://purl.uniprot.org/uniprot/Q9WUL7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||Cytoplasm|||Found in a complex with ARL3, RP2 and UNC119 (or UNC119B); RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119 (or UNC119B). Interacts with RP2; interaction is direct and stimulated with the activated GTP-bound form of ARL3. Interacts with SYS1. Interacts with ARL2BP; the GTP-bound form interacts with ARL2BP. Microtubule-associated protein. Does not interact with TBCC (By similarity). Interacts with RP2 (PubMed:18376416). Interacts with PDE6D; the interaction occurs specifically with the GTP-bound form of ARL3 (PubMed:10518933, PubMed:15979089). Interacts with GGA1; the interaction recruits PKD1:PKD2 complex to trans-Golgi network and is required for ciliary targeting of PKD1:PKD2 complex (PubMed:25405894). Interacts with DNAAF9 (By similarity).|||Golgi apparatus membrane|||Lethality by 3 weeks of age. Mice exhibit abnormal development of renal, hepatic, and pancreatic epithelial tubule structures. Mice show abnormal epithelial cell proliferation and cyst formation. Moreover, they exhibit photoreceptor degeneration as early as postnatal day 14.|||Nucleus|||Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP) (PubMed:18376416). Required for normal cytokinesis and cilia signaling. Required for targeting proteins to the cilium, including myristoylated NPHP3 and prenylated INPP5E. Targets NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (By similarity). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms (PubMed:15979089). Required for PKD1:PKD2 complex targeting from the trans-Golgi network to the cilium (PubMed:25405894).|||centrosome|||cilium|||spindle http://togogenome.org/gene/10090:Exoc3l4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0W9|||http://purl.uniprot.org/uniprot/Q6DIA2 ^@ Similarity ^@ Belongs to the SEC6 family. http://togogenome.org/gene/10090:Cep68 ^@ http://purl.uniprot.org/uniprot/Q8C0D9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with CNTLN; the interaction recruits CEP68 to the centrosome. Interacts with the SCF(FBXW11) complex which contains SKP1, CUL1 and FBXW11; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT. Also interacts with F-box protein BTRC. Interacts with serine/threonine-protein kinase PLK1; the interaction leads to phosphorylation of CEP68 and its subsequent degradation. Interacts with NEK2; the interaction leads to phosphorylation of CEP68.|||Involved in maintenance of centrosome cohesion, probably as part of a linker structure which prevents centrosome splitting. Required for localization of CDK5RAP2 to the centrosome during interphase. Contributes to CROCC/rootletin filament formation.|||Phosphorylation by PLK1 is required for binding to BTRC in prometaphase. Phosphorylated directly or indirectly by NEK2. NEK2-mediated phosphorylation promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis.|||Ubiquitinated and targeted for proteasomal degradation in early mitosis by the SCF(BTRC) and/or SCF(FBXW11) E3 ubiquitin-protein ligase complexes. Degradation is complete by prometaphase and is required for removal of CDK5RAP2 from the peripheral pericentriolar material and subsequent centriole separation.|||centrosome http://togogenome.org/gene/10090:Intu ^@ http://purl.uniprot.org/uniprot/Q059U7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inturned family.|||Cell surface|||Cytoplasm|||Embryos die at midgestation. Embryos exhibit multiple defects including neural tube closure defects, abnormal dorsal/ventral patterning of the central nervous system and abnormal anterior-posterior patterning of the limbs resulting in severe polydactyly. Fewer and shorter cilia are present in mutant embryos. In mice lacking both Intu and Fuz, the lack of convergent extension and more severe patterning defects in Intu and Fuz mutants does not result from a functional redundancy between these proteins.|||Interacts with CPLANE1. Interacts with FUZ and WDPCP; FUZ, INTU and WDPCP probably form the core CPLANE (ciliogenesis and planar polarity effectors) complex.|||Plays a key role in ciliogenesis and embryonic development. Regulator of cilia formation by controlling the organization of the apical actin cytoskeleton and the positioning of the basal bodies at the apical cell surface, which in turn is essential for the normal orientation of elongating ciliary microtubules. Plays a key role in definition of cell polarity via its role in ciliogenesis but not via conversion extension. Has an indirect effect on hedgehog signaling (PubMed:20067783, PubMed:21761479). Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (By similarity).|||Widely expressed in E8.5 and E9.5 wild type embryos. Present in various adult organs (at protein level).|||cilium basal body http://togogenome.org/gene/10090:Asxl3 ^@ http://purl.uniprot.org/uniprot/Q8C4A5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Asx family.|||Nucleus|||Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility (By similarity). http://togogenome.org/gene/10090:Akr1cl ^@ http://purl.uniprot.org/uniprot/G3XA14|||http://purl.uniprot.org/uniprot/Q3UXL1|||http://purl.uniprot.org/uniprot/Q9D5U2 ^@ Similarity ^@ Belongs to the aldo/keto reductase family. http://togogenome.org/gene/10090:Spem1 ^@ http://purl.uniprot.org/uniprot/Q5F289 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Membrane|||Mice are completely infertile because of deformed sperm characterized by a bent head wrapped around by the neck and the middle piece of the tail. Lack of Spem1 causes failure of the cytoplasm to become loose and detach from the head and the neck region of the developing spermatozoa.|||Required for proper cytoplasm removal during spermatogenesis.|||Testis-specific. Exclusively present in cytoplasm of steps 14-16 elongated spermatids (at protein level). http://togogenome.org/gene/10090:Rnaseh2a ^@ http://purl.uniprot.org/uniprot/Q9CWY8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase HII family. Eukaryotic subfamily.|||Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.|||Manganese or magnesium. Binds 1 divalent metal ion per monomer in the absence of substrate. May bind a second metal ion after substrate binding.|||Nucleus|||The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C. http://togogenome.org/gene/10090:Nmral1 ^@ http://purl.uniprot.org/uniprot/Q8K2T1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NmrA-type oxidoreductase family.|||Cytoplasm|||Homodimer. Interacts with ASS1. Interaction is enhanced by low NADPH/NADP(+) ratios, which results in inhibition of ASS1 activity (By similarity).|||Lacks the conserved Tyr residue in the active site triad of Ser-Tyr-Lys necessary for dehydrogenase activity, suggesting that it has no oxidoreductase activity.|||Nucleus|||Redox sensor protein. Undergoes restructuring and subcellular redistribution in response to changes in intracellular NADPH/NADP(+) levels. At low NADPH concentrations the protein is found mainly as a monomer, and binds argininosuccinate synthase (ASS1), the enzyme involved in nitric oxide synthesis. Association with ASS1 impairs its activity and reduces the production of nitric oxide, which subsecuently prevents apoptosis. Under normal NADPH concentrations, the protein is found as a dimer and hides the binding site for ASS1. The homodimer binds one molecule of NADPH. Has higher affinity for NADPH than for NADP(+). Binding to NADPH is necessary to form a stable dimer (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Gng4 ^@ http://purl.uniprot.org/uniprot/P50153 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G protein gamma family.|||Brain.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma. Interacts with beta-1 and beta-2, but not with beta-3 (By similarity). Interacts with KCNK1.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Hmgb3 ^@ http://purl.uniprot.org/uniprot/O54879|||http://purl.uniprot.org/uniprot/Q544R9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HMGB family.|||Chromosome|||Cytoplasm|||Expressed in bone marrow cells, specifically in primitive Lin-, c-kit+, Sca-1+, IL-7Ralpha- cells, and Ter119+ erythroid cells (PubMed:12714519).|||Highly expressed in the embryo; barely detectable in the adult stage.|||Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. Associates with chromatin and binds DNA with a preference for non-canonical DNA structures such as single-stranded DNA. Can bend DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters (By similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor (PubMed:19890330). Negatively regulates B-cell and myeloid cell differentiation. In hematopoietic stem cells may regulate the balance between self-renewal and differentiation. Involved in negative regulation of canonical Wnt signaling (PubMed:12714519, PubMed:15358624, PubMed:16945912).|||Nucleus|||Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-104 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB3 (HMGB3C23hC45hC104h), 2- disulfide HMGB3 (HMGB3C23-C45C104h) and 3- sulfonyl HMGB3 (HMGB3C23soC45soC104so). http://togogenome.org/gene/10090:Or5p63 ^@ http://purl.uniprot.org/uniprot/Q7TRU9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dxo ^@ http://purl.uniprot.org/uniprot/A0A0R4J288|||http://purl.uniprot.org/uniprot/O70348 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DXO/Dom3Z family.|||Binds 2 magnesium ions.|||Decapping enzyme for NAD-capped RNAs: specifically hydrolyzes the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA (PubMed:28283058, PubMed:32374864). The NAD-cap is present at the 5'-end of some RNAs and snoRNAs (PubMed:28283058). In contrast to the canonical 5'-end N7 methylguanosine (m7G) cap, the NAD cap promotes mRNA decay (PubMed:28283058). Preferentially acts on NAD-capped transcripts in response to environmental stress (By similarity). Also acts as a non-canonical decapping enzyme that removes the entire cap structure of m7G capped or incompletely capped RNAs and mediates their subsequent degradation (PubMed:23523372, PubMed:28283058). Specifically degrades pre-mRNAs with a defective 5'-end m7G cap and is part of a pre-mRNA capping quality control (PubMed:23523372). Has decapping activity toward incomplete 5'-end m7G cap mRNAs such as unmethylated 5'-end-capped RNA (cap0), while it has no activity toward 2'-O-ribose methylated m7G cap (cap1) (PubMed:23523372). In contrast to canonical decapping enzymes DCP2 and NUDT16, which cleave the cap within the triphosphate linkage, the decapping activity releases the entire cap structure GpppN and a 5'-end monophosphate RNA (PubMed:23523372). Also has 5'-3' exoribonuclease activities: The 5'-end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs (PubMed:23523372, PubMed:30180947). Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5'-end triphosphate to release pyrophosphates (PubMed:23523372). Exhibits decapping activity towards FAD-capped RNAs (PubMed:32432673, PubMed:32374864). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (PubMed:32432673, PubMed:32374864).|||Decapping enzyme for NAD-capped RNAs: specifically hydrolyzes the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA.|||Nucleus|||The 5'-3' exoribonuclease activity is inhibited by adenosine 3',5'-bisphosphate. http://togogenome.org/gene/10090:Or9s14 ^@ http://purl.uniprot.org/uniprot/Q8VFC5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Parp6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0T1|||http://purl.uniprot.org/uniprot/G5E856|||http://purl.uniprot.org/uniprot/Q6P6P7 ^@ Function|||PTM|||Similarity ^@ Auto-mono-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. http://togogenome.org/gene/10090:Cadm2 ^@ http://purl.uniprot.org/uniprot/Q8BLQ9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Adhesion molecule that engages in homo- and heterophilic interactions with the other nectin-like family members, leading to cell aggregation. Important for synapse organization, providing regulated trans-synaptic adhesion. Preferentially binds to oligodendrocytes (By similarity).|||Belongs to the nectin family.|||Cell membrane|||Glycosylation at Asn-51 reduces adhesive binding.|||Synapse|||axon http://togogenome.org/gene/10090:Slc5a4b ^@ http://purl.uniprot.org/uniprot/Q2VPB3|||http://purl.uniprot.org/uniprot/Q91ZP4 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Expressed in small intestine (PubMed:22301059). Expressed in kidney (PubMed:12969150).|||Inhibited by phlorizin.|||Low-affinity sodium/D-glucose symporter (Probable) (PubMed:22301059). Generates D-glucose-induced depolarization in a pH-independent manner (PubMed:22301059).|||Membrane|||Significantly increased by cadnium. http://togogenome.org/gene/10090:Azi2 ^@ http://purl.uniprot.org/uniprot/Q9QYP6 ^@ Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein which binds TBK1 and IKBKE playing a role in antiviral innate immunity. Activates serine/threonine-protein kinase TBK1 and facilitates its oligomerization. Enhances the phosphorylation of NF-kappa-B p65 subunit RELA by TBK1. Promotes TBK1-induced as well as TNF-alpha or PMA-induced activation of NF-kappa-B. Participates in IFNB promoter activation via TICAM1.|||By 5-azacytidine.|||Cytoplasm|||Homodimer (PubMed:17568778). Interacts with IKBKE and TBK1 (PubMed:17568778). Interacts with TICAM1 (By similarity). Interacts with TAX1BP1 (By similarity). Interacts with CALCOCO2 (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Testis, ovary, heart, lung, kidney and brain. Expressed mainly in the spermatocytes or spermatids in the testis.|||Ubiquitinated via 'Lys-48'-linked polyubiquitination by TRIM38, leading to its degradation. http://togogenome.org/gene/10090:Ankrd54 ^@ http://purl.uniprot.org/uniprot/Q91WK7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in a variety of hemopoietic cell lines and tissue with high levels in testis. Highly expressed in ciliated cells.|||Expressed in brachial arches, maxillary process, fore and hind limb buds and in the developing gastrointestinal tract of day 10 embryos.|||Interacts (via ankyrin repeat region) with LYN (via SH3-domain) in an activation-independent status of LYN. Forms a multiprotein complex with LYN and HCLS1. Interacts with TSN2, VAV1, DBNL and LASP1.|||Midbody|||Nucleus|||Plays an important role in regulating intracellular signaling events associated with erythroid terminal differentiation. http://togogenome.org/gene/10090:Cxxc5 ^@ http://purl.uniprot.org/uniprot/Q91WA4 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expressed in dorsal pallium and in and around the developing choroid plexus at 10.5 and 12.5 dpc.|||Interacts with DVL1 (By similarity). Interacts with RBPJ (By similarity).|||May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells. Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis (By similarity). Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (By similarity). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By similarity).|||Nucleus|||The CXXC zinc finger mediates binding to CpG-DNA. http://togogenome.org/gene/10090:Mdga1 ^@ http://purl.uniprot.org/uniprot/D3Z499 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5b117 ^@ http://purl.uniprot.org/uniprot/Q7TQQ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prorp ^@ http://purl.uniprot.org/uniprot/Q8JZY4 ^@ Cofactor|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PPR family. P subfamily.|||Binds 2 Mg(2+) or Mg(2+) ions per subunit.|||Catalytic component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3.|||Catalytic ribonuclease component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP, which cleaves tRNA molecules in their 5'-ends. The presence of TRMT10C/MRPP1, HSD17B10/MRPP2 is required to catalyze tRNA molecules in their 5'-ends.|||Degraded by LONP1 following mitochondrial unfolded protein response, probably leading to inhibit translation in mitochondrion.|||Detected, after the onset of hearing, in the organ of Corti around the afferent and efferent synapses of the inner hair cells and the efferent synapses of the outer hair cells.|||Displays a distorted and non-productive active site that probably switches to a fully productive state only upon association with TRMT10C/MRPP1, HSD17B10/MRPP2 and pre-tRNA substrate.|||Mitochondrion|||Partial sequence. http://togogenome.org/gene/10090:Or5v1 ^@ http://purl.uniprot.org/uniprot/A2RT31 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dnai2 ^@ http://purl.uniprot.org/uniprot/A2AC93 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein intermediate chain family.|||Consists of at least two heavy chains and a number of intermediate and light chains (Probable). Interacts with DNAAF2 (PubMed:19052621). Interacts with DNAAF6/PIH1D3 (PubMed:24421334). Interacts with HEATR2; probably involved in outer arm dynein assembly (By similarity).|||Dynein axonemal particle|||In ovaries, it is detected at high levels in vivo on day 10, with a subsequent decrease on days 15 and 20, in adult and old ovaries. Weakly expressed on day 5.|||Part of the dynein complex of respiratory cilia.|||Predominantly expressed in ovary, testis and lung.|||cilium axoneme http://togogenome.org/gene/10090:Dnah11 ^@ http://purl.uniprot.org/uniprot/E9Q7N9 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Epn2 ^@ http://purl.uniprot.org/uniprot/J3QNT7|||http://purl.uniprot.org/uniprot/Q5NCM7|||http://purl.uniprot.org/uniprot/Q8CHU3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the epsin family.|||Binds EPS15, AP-2 and clathrin (By similarity). Interacts with UBQLN2 (By similarity). Interacts with ITSN1.|||Cytoplasm|||Plays a role in the formation of clathrin-coated invaginations and endocytosis.|||The DPW repeat domain is involved in AP-2 and clathrin binding.|||The NPF repeat domain is involved in EPS15 binding.|||Ubiquitinated. http://togogenome.org/gene/10090:Rnf7 ^@ http://purl.uniprot.org/uniprot/D3Z392|||http://purl.uniprot.org/uniprot/Q9WTZ1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RING-box family.|||Cytoplasm|||Nucleus|||Probable component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (By similarity). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (By similarity). Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme to the complex and brings it into close proximity to the substrate. Promotes the neddylation of CUL5 via its interaction with UBE2F. May play a role in protecting cells from apoptosis induced by redox agents (By similarity).|||Probable part of SCF complexes, which consist of SKP1, CUL1, RNF7/RBX2 and a F-box protein. Interacts (preferentially) with CUL5. Also interacts (with lower preference) with CUL1, CUL2, CUL3, CUL4A and CUL4B. Interacts with UBE2F (By similarity). May also interact with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (By similarity).|||The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion. http://togogenome.org/gene/10090:Arhgap11a ^@ http://purl.uniprot.org/uniprot/Q80Y19 ^@ Function|||Subcellular Location Annotation ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.|||Nucleus http://togogenome.org/gene/10090:Tmem143 ^@ http://purl.uniprot.org/uniprot/Q8VD26 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or2h1 ^@ http://purl.uniprot.org/uniprot/Q7TRL3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Guca2a ^@ http://purl.uniprot.org/uniprot/P33680 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the guanylin family.|||Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins.|||Localized in both crypts and villi in the small intestine and to superficial epithelial cells in the colon.|||Secreted http://togogenome.org/gene/10090:Parp10 ^@ http://purl.uniprot.org/uniprot/Q8CIE4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate and aspartate residues on target proteins. In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation. Catalyzes mono-ADP-ribosylation of GSK3B, leading to negatively regulate GSK3B kinase activity. Involved in translesion DNA synthesis in response to DNA damage via its interaction with PCNA.|||Auto-mono-ADP-ribosylated on glutamate and lysine residues.|||Belongs to the ARTD/PARP family.|||Cytoplasm|||Interacts with MYC. Interacts with PARP14. Interacts (via-PIP box and ubiquitin-interacting motifs) with PCNA.|||Nucleus|||Stimulated through its phosphorylation by CDK2. Acquires CDK-dependent phosphorylation through late-G1 to S phase, and from prometaphase to cytokinesis in the nucleolar organizing regions. Phosphorylation is suppressed in growth-arrested cells.|||The PIP-box mediates the interaction with PCNA. http://togogenome.org/gene/10090:Slco1a6 ^@ http://purl.uniprot.org/uniprot/Q99J94 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Kidney specific.|||May mediate the Na(+)-independent transport of organic anions.|||Not detected at birth and up to day 20. Intermediate levels were detected at day 40 and adult levels were reached at day 60. http://togogenome.org/gene/10090:Ppfibp2 ^@ http://purl.uniprot.org/uniprot/G3X957|||http://purl.uniprot.org/uniprot/O35711 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the liprin family. Liprin-beta subfamily.|||Due to intron retention.|||Expressed widely. Strong expression in liver, kidney, intestine, heart, lung and testis. Low expression in brain and thymus.|||Forms homodimers and heterodimers.|||Found at 10.5 dpc through 16.5 dpc.|||May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A (By similarity).|||The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type beta/beta. The C-terminal, non-coiled coil regions mediate heterodimerization type beta/alpha (By similarity). http://togogenome.org/gene/10090:Kcng2 ^@ http://purl.uniprot.org/uniprot/F7A6P6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Inpp5e ^@ http://purl.uniprot.org/uniprot/Q9JII1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inositol polyphosphate 5-phosphatase family.|||Cell membrane|||Cytoplasm|||Deficient mice display signs of ciliopathies including prenatal and perinatal lethality, polycystic kidneys, arrest of eye development, abnormalities in primary cilia, cerebral developmental defects, and skeletal defects.|||Golgi stack membrane|||Highly expressed in testis, in pachytene and diplotene spermatocytes, but not in more mature elongating spermatids. Detected in neurons throughout the brain.|||Interacts (when prenylated) with PDE6D; this is important for normal location in cilia.|||Nucleus|||Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Specific for lipid substrates, inactive towards water soluble inositol phosphates. Specific for lipid substrates, inactive towards water soluble inositol phosphates (By similarity) (PubMed:10806194). Plays an essential role in the primary cilium by controlling ciliary growth and phosphoinositide 3-kinase (PI3K) signaling and stability (PubMed:19668215).|||cilium axoneme|||ruffle http://togogenome.org/gene/10090:Tmprss11c ^@ http://purl.uniprot.org/uniprot/Q1JRP2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Expressed specifically in Purkinje neurons of the cerebellum (at protein level). Also detected in spinal cord.|||Perikaryon|||Proteolytically cleaved via an autocatalytic mechanism.|||Serine protease which has a preference for Arg or Lys in position P1 and uncharged residues in positions P2 and P3. Shows specificity towards FGF2 in vitro.|||dendrite http://togogenome.org/gene/10090:Gas2l3 ^@ http://purl.uniprot.org/uniprot/Q3UWW6 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GAS2 family.|||Cytoplasm|||Cytoskeletal linker protein. May promote and stabilize the formation of the actin and microtubule network (By similarity).|||Interacts (via CH domain) with F-actin (By similarity). Interacts (via C terminus) with microtubules (By similarity). Interacts with MAPRE1 (PubMed:24706950).|||It is uncertain whether Met-1 or Met-3 is the initiator.|||The GAR domain modulates the binding strength to each cytoskeletal network.|||cytoskeleton http://togogenome.org/gene/10090:Smcr8 ^@ http://purl.uniprot.org/uniprot/Q3UMB5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMCR8 family.|||Cells lacking display impaired autophagy induction.|||Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27617292). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (By similarity). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (By similarity). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (By similarity). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (By similarity).|||Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (Probable). The complex is formed of two protomers, each individually consisting of one molecule each of C9orf72, SMCR8 and WDR41 (By similarity). The protomers homodimerize via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-terminus) (By similarity). Within each protomer SMCR8 (via DENN domain) acts as a bridging protein between WDR41 (via C-terminus and N-terminus) and C9orf72 (via C-terminus) (By similarity). The C9orf72-SMCR8 complex associates with the ULK1/ATG1 kinase complex (By similarity). Interacts with C9orf72; the interaction is direct (PubMed:27875531). Interacts with DLG4/PSD-95 (PubMed:31651360).|||Cytoplasm|||Nucleus|||Phosphorylation by TBK1 is required to promote autophagosome maturation. Phosphorylated by ULK1.|||Postsynapse|||Presynapse|||Widely expressed (PubMed:11997338). Expressed in the forebrain and hippocampus (at protein level) (PubMed:31651360). http://togogenome.org/gene/10090:Rab14 ^@ http://purl.uniprot.org/uniprot/Q50HX4|||http://purl.uniprot.org/uniprot/Q91V41 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Early endosome membrane|||Endosome membrane|||Golgi apparatus membrane|||Interacts with ZFYVE20 (By similarity). Interacts with KIF16B.|||Recycling endosome|||Regulates, together with its guanine nucleotide exchange factor, DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion (By similarity). Involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development. Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes (By similarity).|||phagosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Il23r ^@ http://purl.uniprot.org/uniprot/Q8K4B4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with IL12RB1 to form the interleukin-23 receptor. Binds IL23 and mediates T-cells, NK cells and possibly certain macrophage/myeloid cells stimulation probably through activation of the Jak-Stat signaling cascade. IL23 functions in innate and adaptive immunity and may participate in acute response to infection in peripheral tissues. IL23 may be responsible for autoimmune inflammatory diseases and be important for tumorigenesis (By similarity).|||Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Cell membrane|||Expressed by Th1, Th2 and dendritic cells.|||Heterodimer with IL12RB1. In presence of IL23, the heterodimer forms the IL23 receptor. Interacts with JAK2 and in presence of IL23 with STAT3 (By similarity).|||Phosphorylated in response to IL23. http://togogenome.org/gene/10090:Canx ^@ http://purl.uniprot.org/uniprot/P35564|||http://purl.uniprot.org/uniprot/Q5SUC3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calreticulin family.|||Calcium-binding protein that interacts with newly synthesized monoglucosylated glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse.|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Expressed in sperm (at protein level).|||Interacts with MAPK3/ERK1 (By similarity). Interacts with KCNH2 (By similarity). Associates with ribosomes (By similarity). The palmitoylated form interacts with the ribosome-translocon complex component SSR1, promoting efficient folding of glycoproteins (By similarity). Interacts with SERPINA2P/SERPINA2 and with the S and Z variants of SERPINA1 (By similarity). Interacts with SGIP1; involved in negative regulation of endocytosis (PubMed:21747946). Interacts with PPIB (By similarity). Interacts with SMIM22 (By similarity). Interacts with TMX2 (By similarity). Interacts with TMEM35A/NACHO (PubMed:32783947). Interacts with CHRNA7 (By similarity). Interacts with reticulophagy regulators RETREG2 and RETREG3 (By similarity). Interacts with DNM1L; may form part of a larger protein complex at the ER-mitochondrial interface during mitochondrial fission (By similarity). Interacts with ADAM7 (PubMed:20945367).|||Melanosome|||Palmitoylation by DHHC6 leads to the preferential localization to the perinuclear rough ER. It mediates the association of calnexin with the ribosome-translocon complex (RTC) which is required for efficient folding of glycosylated proteins (By similarity).|||Phosphorylated at Ser-563 by MAPK3/ERK1. Phosphorylation by MAPK3/ERK1 increases its association with ribosomes (By similarity).|||Ubiquitinated, leading to proteasomal degradation. Probably ubiquitinated by ZNRF4. http://togogenome.org/gene/10090:Sox10 ^@ http://purl.uniprot.org/uniprot/Q04888 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Defects in Sox10 are the cause of the mouse mutant dominant megacolon (dom). While dom/+ heterozygous mice display regional deficiencies of neural crest-derived enteric ganglia in the distal colon, dom/dom homozygous animals are embryonic lethal.|||Expressed in oligodendroglia of the spinal tube (at protein level).|||Expressed in the motor neuron progenitor domain of the spinal tube from 11.5 dpc to postnatal day 6.|||Mitochondrion outer membrane|||Monomer (PubMed:27532821). Interacts with Armcx3 at the mitochondrial outer membrane surface (PubMed:19304657). Interacts with PAX3 (By similarity).|||Nucleus|||The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.|||Transcription factor that plays a central role in developing and mature glia (PubMed:24204311, PubMed:27532821). Specifically activates expression of myelin genes, during oligodendrocyte (OL) maturation, such as DUSP15 and MYRF, thereby playing a central role in oligodendrocyte maturation and CNS myelination (PubMed:24204311, PubMed:27532821). Once induced, MYRF cooperates with SOX10 to implement the myelination program (PubMed:24204311). Transcriptional activator of MITF, acting synergistically with PAX3 (By similarity). Transcriptional activator of MBP, via binding to the gene promoter (By similarity). http://togogenome.org/gene/10090:Ewsr1 ^@ http://purl.uniprot.org/uniprot/Q5SUT0|||http://purl.uniprot.org/uniprot/Q61545|||http://purl.uniprot.org/uniprot/Q6NVA3 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM TET family.|||Binds RNA, POLR2C, SF1 and calmodulin. Interacts with PTK2B and TDRD3 (By similarity). Forms a complex with REC8, PRDM9, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (PubMed:27932493).|||Binds calmodulin in the presence, but not in the absence, of calcium ion.|||Cell membrane|||Cytoplasm|||Highly methylated on arginine residues. Methylation is mediated by PRMT1 and, at lower level by PRMT8 (By similarity).|||Might function as a transcriptional repressor.|||Nucleus|||Phosphorylated; calmodulin-binding inhibits phosphorylation of Ser-266. http://togogenome.org/gene/10090:Tmem170b ^@ http://purl.uniprot.org/uniprot/P86050 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM170 family.|||Cell membrane|||Interacts with CTNNB1. http://togogenome.org/gene/10090:Eif3h ^@ http://purl.uniprot.org/uniprot/Q5M9L0|||http://purl.uniprot.org/uniprot/Q91WK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit H family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with RNF139; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with RNF139; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner (By similarity). Interacts with DHX33; the interaction is independent of RNA (PubMed:26100019).|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm http://togogenome.org/gene/10090:Spast ^@ http://purl.uniprot.org/uniprot/A0A286YE25|||http://purl.uniprot.org/uniprot/Q9QYY8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:19141076, PubMed:20530212). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Severing activity is not dependent on tubulin acetylation or detyrosination (By similarity). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation (By similarity). It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia (By similarity). SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (By similarity). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (By similarity). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (By similarity). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (By similarity). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (By similarity). Probably plays a role in axon growth and the formation of axonal branches (PubMed:18234839).|||ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Severing activity is not dependent on tubulin acetylation or detyrosination. Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex. Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex. Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling. Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing. Probably plays a role in axon growth and the formation of axonal branches.|||Allosteric enzyme with a cooperative mechanism; at least two neighbor subunits influence each other strongly in spastin hexamers. Microtubule binding promotes cooperative interactions among spastin subunits.|||Belongs to the AAA ATPase family. Spastin subfamily.|||Cytoplasm|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Endosome|||Expressed in brain, heart, liver, lung, skeletal muscle, spinal cord, spleen and testis.|||Expressed is decreased following activation of the Notch pathway by JAG1/Jagged1.|||Homohexamer. Mostly monomeric, but assembles into hexameric structure for short periods of time. Oligomerization seems to be a prerequisite for catalytic activity. Binding to ATP in a cleft between two adjacent subunits stabilizes the homohexameric form. Binds to microtubules at least in part via the alpha-tubulin and beta-tubulin tails. The hexamer adopts a ring conformation through which microtubules pass prior to being severed. Does not interact strongly with tubulin heterodimers. Interacts (via MIT domain) with CHMP1B; the interaction is direct. Interacts with SSNA1. Interacts with ATL1. Interacts with RTN1. Interacts with ZFYVE27. Interacts with REEP1. Interacts (via MIT domain) with IST1.|||Involved in lipid metabolism by regulating the size and distribution of lipid droplets.|||Lipid droplet|||Membrane|||Mice develop gait abnormalities that correlate with phenotypes seen in hereditary spastic paraplegia (HSP) patients (PubMed:19453301). Adults are sterile (PubMed:17101632). Progressive axonal degeneration characterized by focal axonal swellings and the accumulation of organelles and cytoskeletal components, which is suggestive of impaired axonal transport (PubMed:17101632, PubMed:19453301). Primary cortical neurons develop swellings at the border between stable and dynamic microtubules (PubMed:17101632). In neurons with axonal swellings, the mitochondrial axonal transport defects are exacerbated: distal to axonal swellings both anterograde and retrograde transport are severely reduced (PubMed:19453301). In cortical neurons, axonal swellings is probably due to impaired microtubule dynamics all along the axons (PubMed:22773755).|||Midbody|||Nucleus|||Nucleus membrane|||axon|||centrosome|||cytoskeleton|||perinuclear region|||spindle http://togogenome.org/gene/10090:Rhog ^@ http://purl.uniprot.org/uniprot/P84096 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Interacts with ARHGEF26 (By similarity). Interacts with ARHGEF16 (By similarity). Interacts with UNC13D; the interaction increases RhoG affinity to the membrane lipids, targets UNC13D to membrane lipids and facilitates cytotoxic granule (CG) docking to the plasma membrane (By similarity).|||Plays a role in immunological synaptic F-actin density and architecture organization (By similarity). Regulates actin reorganization in lymphocytes, possibly through the modulation of Rac1 activity (By similarity). Required for the formation of membrane ruffles during macropinocytosis (By similarity). Plays a role in cell migration and is required for the formation of cup-like structures during trans-endothelial migration of leukocytes (By similarity). Binds phospholipids in an activation-dependent manner; thereby acting as an anchor for other proteins to the plasma membrane (PM) (By similarity). Plays a role in exocytosis of cytotoxic granules (CG) by lymphocytes/Component of the exocytosis machinery in natural killer (NK) and CD8+ T cells (By similarity). Promotes the docking of cytotoxic granules (CG) to the plasma membrane through the interaction with UNC13D (By similarity). Involved in the cytotoxic activity of lymphocytes/primary CD8+ T cells (By similarity). http://togogenome.org/gene/10090:Yif1a ^@ http://purl.uniprot.org/uniprot/Q91XB7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the YIF1 family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||Interacts with YIPF5.|||Possible role in transport between endoplasmic reticulum and Golgi. http://togogenome.org/gene/10090:H4c2 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Phf12 ^@ http://purl.uniprot.org/uniprot/Q5SPL2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. Involved in recruitment of functional SIN3A complexes to DNA. Represses transcription at least in part through the activity of an associated histone deacetylase (HDAC). May also repress transcription in a SIN3A-independent manner through recruitment of functional TLE5 complexes to DNA (By similarity).|||Expressed mainly in heart, brain, lung, liver and testis.|||Expression is low in day 7 embryos, peaks at day 11 and declines through to day 17.|||Interacts with SIN3A in a complex composed of HDAC1, SAP30 and SIN3A. Interacts with TLE5 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Rbl1 ^@ http://purl.uniprot.org/uniprot/Q64701|||http://purl.uniprot.org/uniprot/Q6PAR4 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the retinoblastoma protein (RB) family.|||Cell-cycle arrest properties are inactivated by phosphorylation on Thr-332, Ser-640, Ser-959 and Ser-970 by CDK4.|||Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2 (By similarity). The complex exists in quiescent cells where it represses cell cycle-dependent genes (By similarity). It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity). Interacts with AATF (By similarity). Interacts with KDM5A (By similarity). Interacts with KMT5B and KMT5C (PubMed:11571651). Interacts with USP4 (PubMed:15750587). Interacts with RBBP9 (By similarity).|||Highly expressed in fetal heart and liver. Expressed at low levels in all other fetal tissues except skeletal muscle. High levels in neonatal spleen and thymus with low levels in other tissues. In adult, highly expressed in testis. Barely detectable in other tissues.|||Highly expressed in fetal tissues. Expression markedly decreased in adult.|||Key regulator of entry into cell division (By similarity). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (PubMed:15750587). Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression (PubMed:15750587). Controls histone H4 'Lys-20' trimethylation (PubMed:15750587). Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters (PubMed:15750587). Potent inhibitor of E2F-mediated trans-activation (By similarity). May act as a tumor suppressor (By similarity).|||Nucleus http://togogenome.org/gene/10090:Mien1 ^@ http://purl.uniprot.org/uniprot/Q9CQ86 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SelWTH family.|||Cell membrane|||Increases cell migration by inducing filopodia formation at the leading edge of migrating cells. Plays a role in regulation of apoptosis, possibly through control of CASP3. May be involved in a redox-related process (By similarity).|||Interacts with GPX1.|||Isoprenylation facilitates association with the plasma membrane and enhances the migratory phenotype of cells by inducing increased filopodia formation.|||Widely expressed with highest levels in kidney followed by brain and testis.|||cytosol http://togogenome.org/gene/10090:Lhfpl3 ^@ http://purl.uniprot.org/uniprot/A0A0G2JGI3|||http://purl.uniprot.org/uniprot/Q9CTN8 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LHFP family.|||Brain-specific.|||Membrane http://togogenome.org/gene/10090:Rarb ^@ http://purl.uniprot.org/uniprot/P22605|||http://purl.uniprot.org/uniprot/Q6DFX0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Homodimer (By similarity). Heterodimer; with a RXR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Heterodimerizes (via NR LBD) with RXRA (By similarity). Interacts weakly with NCOR2 (By similarity).|||Nucleus|||Rarb and Rarg, but not Rarb and Rara, double null mice exhibit growth retardation 3 weeks after birth. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed. Isoform 2 mutants appear normal.|||Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (By similarity). The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element (By similarity). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (PubMed:19389355).|||The DNA-binding nuclear receptor domain and the NR LBD domain are required for binding of the RARB/RXRA heterodimer to both DR1 and DR5 DNA elements. http://togogenome.org/gene/10090:Matk ^@ http://purl.uniprot.org/uniprot/A0A0R4J1N6|||http://purl.uniprot.org/uniprot/A0A0R4J1P8|||http://purl.uniprot.org/uniprot/D3Z4T5|||http://purl.uniprot.org/uniprot/P41242 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.|||Could play a significant role in the signal transduction of hematopoietic cells. May regulate tyrosine kinase activity of SRC-family members in brain by specifically phosphorylating their C-terminal regulatory tyrosine residue which acts as a negative regulatory site. It may play an inhibitory role in the control of T-cell proliferation.|||Cytoplasm|||Interacts with KIT.|||Membrane|||Minor isoform.|||Most abundant in brain, and to a lesser extent in the spleen, the thymus and the liver. Also found in the T-cell lineage. http://togogenome.org/gene/10090:Polrmt ^@ http://purl.uniprot.org/uniprot/Q3U3J3|||http://purl.uniprot.org/uniprot/Q3V3C0|||http://purl.uniprot.org/uniprot/Q8BKF1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phage and mitochondrial RNA polymerase family.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.|||DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA. In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Has DNA primase activity. Catalyzes the synthesis of short RNA primers that are necessary for the initiation of lagging-strand DNA synthesis from the origin of light-strand DNA replication (OriL).|||Homodimer. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (By similarity). Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT. Interacts with TFB1M and TFB2M, leading to the stimulation of transcription. Interacts with TEFM. Interacts with MTRES1 (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:St6gal1 ^@ http://purl.uniprot.org/uniprot/Q64685|||http://purl.uniprot.org/uniprot/Q8BM62 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 29 family.|||Golgi stack membrane|||Membrane|||Monomer and homodimer.|||N-glycosylated.|||Secreted|||The soluble form derives from the membrane form by proteolytic processing.|||Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. http://togogenome.org/gene/10090:Cdc26 ^@ http://purl.uniprot.org/uniprot/Q99JP4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDC26 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex (By similarity).|||Nucleus|||V-shaped homodimer. Interacts with CDC16. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. http://togogenome.org/gene/10090:Snx10 ^@ http://purl.uniprot.org/uniprot/Q3UBN7|||http://purl.uniprot.org/uniprot/Q4FJX6|||http://purl.uniprot.org/uniprot/Q9CWT3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sorting nexin family.|||Cytoplasm|||Endosome membrane|||Expressed in femur, calvariae and teeth.|||Interacts with ATP6V1D; may play a role in ciliogenesis.|||Membrane|||Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption.|||Strongly up-regulated during osteoclastogenesis. Expressed in calvariae and developing teeth as early as 16.5 dpc (at protein level).|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate.|||centrosome http://togogenome.org/gene/10090:Vmn1r32 ^@ http://purl.uniprot.org/uniprot/Q8R2D9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Coq10b ^@ http://purl.uniprot.org/uniprot/A0A0R4J066|||http://purl.uniprot.org/uniprot/G5E8J7|||http://purl.uniprot.org/uniprot/Q3THF9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COQ10 family.|||Interacts with coenzyme Q.|||Mitochondrion inner membrane|||Required for the function of coenzyme Q in the respiratory chain. May serve as a chaperone or may be involved in the transport of Q6 from its site of synthesis to the catalytic sites of the respiratory complexes (By similarity).|||Required for the function of coenzyme Q in the respiratory chain. May serve as a chaperone or may be involved in the transport of Q6 from its site of synthesis to the catalytic sites of the respiratory complexes. http://togogenome.org/gene/10090:Gprc6a ^@ http://purl.uniprot.org/uniprot/Q8K4Z6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Deficient mice shown normal body weight, an increased fat mass, decreased lean body, hyperglycemia and insulin resistance, proteinuria, renal calcium, phosphate wasting, impaired bone mineral density and defective testicular function (PubMed:19050760, PubMed:20947496). Conditional deletion in Leydig cells leads to decreased male fertility (PubMed:21333348).|||Expressed at high level in liver, lung, spleen and heart. Expressed at lower level in kidney, skeletal muscle and brain. Expressed in 7 dpc, 11 dpc, 15 dpc and 17 dpc embryos.|||Homodimer; disulfide-linked.|||N-glycosylated.|||Receptor activated by multiple ligands, including osteocalcin (BGLAP), basic amino acids, and various cations (PubMed:15576628, PubMed:16199532, PubMed:21333348). Activated by amino acids with a preference for basic amino acids such as L-Lys, L-Arg and L-ornithine but also by small and polar amino acids (PubMed:15576628). The L-alpha amino acids respond is augmented by divalent cations Ca(2+) and Mg(2+) (PubMed:16199532). Seems to act through a G(q)/G(11) and G(i)-coupled pathway (PubMed:15576628, PubMed:16199532). Regulates testosterone production by acting as a ligand for uncarboxylated osteocalcin hormone: osteocalcin-binding at the surface of Leydig cells initiates a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner (PubMed:21333348). Mediates the non-genomic effects of androgens in multiple tissue (PubMed:19050760). May coordinate nutritional and hormonal anabolic signals through the sensing of extracellular amino acids, osteocalcin, divalent ions and its responsiveness to anabolic steroids (PubMed:19050760, PubMed:20947496). http://togogenome.org/gene/10090:BC031181 ^@ http://purl.uniprot.org/uniprot/Q91WE4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UPF0729 family.|||Endoplasmic reticulum|||Interacts with DERL1 and AMFR.|||Lipid droplet|||May activate the NF-kappa-B signaling pathway.|||Undergoes ER-associated degradation (ERAD). http://togogenome.org/gene/10090:Samt2b ^@ http://purl.uniprot.org/uniprot/Q9D519 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Slc22a7 ^@ http://purl.uniprot.org/uniprot/Q91WU2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant expression in male and female kidney (PubMed:12065749). In kidney, expressed at the brush border of the proximal tubule S3 segment (S3) in the outer stripe and medullary rays (PubMed:16256982, PubMed:16885152). In kidney, expression is higher in female than male (PubMed:16885152). Also expressed in female liver (PubMed:12065749).|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Functions as a Na(+)-independent bidirectional multispecific transporter (PubMed:12065749). Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively (PubMed:12065749). Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides, and nucleotides with cGMP, 2'deoxyguanosine and GMP being the preferred substrates (By similarity). Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways (By similarity). Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood (By similarity). Involved in renal secretion and possible reabsorption of creatinine (By similarity). Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate (PubMed:12065749). Unlike human hortolog, able to transport glutarate (PubMed:12065749). Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified (By similarity).|||Involved in the uptake of clinically used drugs such as bumetanide, and contributes to renal and hepatic drug elimination. http://togogenome.org/gene/10090:Il1rapl2 ^@ http://purl.uniprot.org/uniprot/Q0VBP3|||http://purl.uniprot.org/uniprot/Q9ERS6 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the interleukin-1 receptor family.|||Detected in fetal brain after day 12.5, in particular in parts of the diencephalon and in the basal plate of the spinal cord. In postnatal brain detected in cerebral cortex, olfactory bulb, in the CA1 region of the hippocampus and in Purkinje cells of the Xth cerebellar lobule.|||May be due to an intron retention.|||Membrane|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. http://togogenome.org/gene/10090:Or2a20 ^@ http://purl.uniprot.org/uniprot/Q8VF17 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or12d2 ^@ http://purl.uniprot.org/uniprot/B2RT33 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trappc12 ^@ http://purl.uniprot.org/uniprot/Q8K2L8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the TRAPP complex, which is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage. Also plays a role in chromosome congression, kinetochore assembly and stability and controls the recruitment of CENPE to the kinetochores.|||Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12. Interacts with CENPE.|||Endoplasmic reticulum-Golgi intermediate compartment|||Nucleus|||Phosphorylated as the cells enter mitosis but is dephosphorylated at or before the onset of anaphase. The phosphorylated form recruits CENPE to kinetochores more efficiently than the non-phosphorylated form. http://togogenome.org/gene/10090:Ly6k ^@ http://purl.uniprot.org/uniprot/Q9CWP4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Interacts with ADAM3 and TEX101.|||Knockout Ly6k mice are viable and show no overt developmental abnormalities. Males are infertile.|||Membrane raft|||Required for sperm migration into the oviduct and male fertility by controlling binding of sperm to zona pellucida (PubMed:24501175). May play a role in cell growth (By similarity).|||Secreted|||Strongly expressed in testes and weakly expressed in the epididymis, ovary, and uterus (PubMed:20920470). Expressed in testicular germ cells (TGCs) (PubMed:24501175). Expressed in the testicular seminiferous tubules, in spermatocytes, spermatids, and testicular spermatozoa (PubMed:27005865).|||Weakly expressed in testes from 18 day postcoitus to 1 day postpartum (dpp), with a plateau starting around 8 dpp; and testicular expression shows two-peak expression at around 14 dpp and 24 dpp, then exhibits stable expression from 6-week after birth onward.|||acrosome http://togogenome.org/gene/10090:Naga ^@ http://purl.uniprot.org/uniprot/Q3U6T2|||http://purl.uniprot.org/uniprot/Q9QWR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 27 family.|||Homodimer.|||Lysosome|||Removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides. Required for the breakdown of glycolipids. http://togogenome.org/gene/10090:Or4x11 ^@ http://purl.uniprot.org/uniprot/Q8VEZ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ap3b2 ^@ http://purl.uniprot.org/uniprot/A0A571BES1|||http://purl.uniprot.org/uniprot/Q9JME5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (By similarity). AP-3 associates with the BLOC-1 complex.|||Belongs to the adaptor complexes large subunit family.|||Golgi apparatus|||Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Slc25a19 ^@ http://purl.uniprot.org/uniprot/A2A9V5|||http://purl.uniprot.org/uniprot/Q80XJ6|||http://purl.uniprot.org/uniprot/Q9DAM5 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Deficient mice are embryonically lethal, with death occurring on or before day 11 of the embryo development. Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations and anemia.|||Membrane|||Mitochondrial transporter mediating uptake of thiamine diphosphate into mitochondria. It is not clear if the antiporter activity is affected by the membrane potential or by the proton electrochemical gradient.|||Mitochondrion membrane|||Previously identified as the mitochondrial deoxyribonucleotide carrier. However other experiments later demonstrated that SLC25A19 is a thiamine diphosphate transporter and not a mitochondrial deoxyribonucleotide carrier. http://togogenome.org/gene/10090:Ucp1 ^@ http://purl.uniprot.org/uniprot/P12242 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Expressed in brown adipose tissue.|||Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it (PubMed:23063128). Activated by noradrenaline and reactive oxygen species (PubMed:27027295). Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-254' (PubMed:32358195). Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS) (PubMed:32358195).|||May undergo ubiquitin-mediated proteasomal degradation.|||Mice lacking Ucp1 display an absence of adaptive thermogenesis in response to cold. Compared to wild-type mice, they are sensitive to cold and consume less oxygen upon treatment with beta-3-adrenergic-receptor agonists that normally activate thermogenesis (PubMed:9139827, PubMed:19187776). They also display impaired adaptive thermogenesis in response to diet variation (PubMed:19187776). If they display lipid accumulation in adipocytes of brown adipose tissues, no overt obesity is observed when mice are housed under classical conditions, i.e. 18 to 20 degrees Celsius (PubMed:9139827). However, when mice are housed at thermoneutrality, i.e. at 30 degrees Celsius, obesity is clearly observed and exacerbated by high fat diet (PubMed:19187776). The brown adipose tissue of mice lacking Ucp1 produce higher levels of reactive oxygen species (PubMed:20416274, PubMed:20466728).|||Mitochondrial transporter that functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP (PubMed:23063128). Responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance (PubMed:9139827, PubMed:19187776, PubMed:23063128, PubMed:27027295). Regulates the production of reactive oxygen species/ROS by mitochondria (PubMed:20416274, PubMed:20466728).|||Mitochondrion inner membrane|||Most probably functions as a monomer. Binds one purine nucleotide per monomer. However, has also been suggested to function as a homodimer or a homotetramer. Tightly associates with cardiolipin in the mitochondrion inner membrane; may stabilize and regulate its activity.|||Sulfenylation at Cys-254 is increased upon cold exposure. It increases the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects.|||Up-regulated in response to cold in brown adipose tissue where it may regulate non-shivering thermogenesis (at protein level) (PubMed:20466728, PubMed:25578880). Up-regulated by high-fat diet (at protein level) (PubMed:19187776). http://togogenome.org/gene/10090:Mau2 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLR7|||http://purl.uniprot.org/uniprot/Q9D2X5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCC4/mau-2 family.|||Chromosome|||Heterodimerizes with MAU2/SCC2 to form the cohesin loading complex. The NIPBL-MAU2 heterodimer interacts with the SMC1A-SMC3 heterodimer and with the cohesin complex composed of SMC1A, SMC3, RAD21 and STAG1.|||Nucleus|||Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodim. eric complex (also known as cohesin loading complex) with NIPBL/SCC2 which mediates the loading of the cohesin complex onto chromatin Plays a role in sister chromatid cohesion and normal progression through prometaphase.|||Spermatocytes and oocytes (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Slc25a32 ^@ http://purl.uniprot.org/uniprot/Q3UM21|||http://purl.uniprot.org/uniprot/Q8BMG8 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Embryonic lethal (PubMed:29666258, PubMed:35727412). At 11.5 dpc, the majority of mutant embryos show neural tube defects with exencephaly or craniorachischisis associated with multiple acyl-CoA dehydrogenase deficiency. Neural tube defects can be prevented by formate supplementation in early embryogenesis.|||Facilitates flavin adenine dinucleotide (FAD) translocation across the mitochondrial inner membrane into the mitochondrial matrix where it acts as a redox cofactor to assist flavoenzyme activities in fundamental metabolic processes including fatty acid beta-oxidation, amino acid and choline metabolism as well as mitochondrial electron transportation. In particular, provides FAD to DLD dehydrogenase of the glycine cleavage system, part of mitochondrial one-carbon metabolic pathway involved in neural tube closure in early embryogenesis.|||Initially postulated to function as a folate transporter based on complementation evidence, but it was latter shown that it rather function as a FAD transporter indirectly affecting folate-mediated one-carbon metabolism in mitochondria.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or1j18 ^@ http://purl.uniprot.org/uniprot/Q8VGK2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem53 ^@ http://purl.uniprot.org/uniprot/Q9D0Z3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM53 family.|||Expressed in calvaria at 16.5 dpc.|||Expressed in liver (at protein level).|||Knockout mice do not display severe skeletal abnormity at birth, but exhibit late-onset short stature. They show craniofacial dysmorphias, including hypertelorism, thickening of the calvaria and minor sclerosis of the skull base. Platyspondyly is also observed, as well as short limbs and underconstriction of the diaphyses.|||Negatively regulates bone morphogenetic protein (BMP) signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of phosphorylated SMAD1/5/9 proteins.|||Nucleus outer membrane http://togogenome.org/gene/10090:Sp8 ^@ http://purl.uniprot.org/uniprot/Q8BMJ8 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Expression is detected in the forebrain, midbrain/hindbrain boundary and neural tube. At the stage of limb bud outgrowth, expressed in a scattered manner in the ventral ectoderm, and is later confined to the apical ectodermal ridge (AER).|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos. http://togogenome.org/gene/10090:Pak6 ^@ http://purl.uniprot.org/uniprot/Q3ULB5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Phosphorylated by MAP2K6/MAPKK6, leading to PAK6 activation (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with the androgen receptor AR. Interacts with IQGAP1 and PPM1B (By similarity).|||Nucleus|||Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD (By similarity). http://togogenome.org/gene/10090:Fam168b ^@ http://purl.uniprot.org/uniprot/E9Q917|||http://purl.uniprot.org/uniprot/G3UWF0|||http://purl.uniprot.org/uniprot/Q80XQ8 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM168 family.|||Cell membrane|||Inhibitor of neuronal axonal outgrowth. Acts as a negative regulator of CDC42 and STAT3 and a positive regulator of STMN2. Positive regulator of CDC27.|||May form homodimers (By similarity). May interact with DAZAP2, FAM168A, PRDX6, RBM6, TMTC1 and YPEL2 (By similarity). Interacts with CDC27 (PubMed:20716133).|||N-glycosylated.|||Predominantly expressed in the brain, including olfactory bulb, cortex and cerebellum (at protein level).|||Specifically expressed in differentiated neurons, but absent from proliferating neural stem cells.|||Up-regulated by different neurotrophins, including NGF and BDNF, but not by growth factors, such as EGF.|||axon|||perinuclear region http://togogenome.org/gene/10090:Lrit3 ^@ http://purl.uniprot.org/uniprot/W8DXL4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in the outer plexiform layer (OPL) of the retina, where it localizes to rod and cone ON-bipolar cells (at protein level). Also detected in bipolar cell bodies in the inner retinal layer (INL) (at protein level).|||Endoplasmic reticulum membrane|||Perikaryon|||Plays a role in the synapse formation and synaptic transmission between cone photoreceptor cells and retinal bipolar cells (PubMed:25997951, PubMed:26427409, PubMed:28334377). Required for normal transmission of a light-evoked stimulus from the cone photoreceptor cells to the ON-bipolar cells and ON-ganglion cells in the inner retina (PubMed:26427409, PubMed:28334377). Required in retinal ON-bipolar cells for normal localization of the cation channel TRPM1 at dendrite tips (PubMed:25997951). Seems to play a specific role in synaptic contacts made by ON-bipolar cells with cone photoreceptor pedicles (PubMed:28334377). May also have a role in cone synapse formation (PubMed:25997951, PubMed:28334377). Might facilitate FGFR1 exit from the endoplasmic reticulum to the Golgi (By similarity). Could be a regulator of the FGFRs (By similarity).|||Viable. Retinal anatomy is grossly normal, although thickness of the INL is reduced. In addition thickness of the innermost region consisting of the inner plexiform layer, ganglion cell layer and optic nerve fiber layer (IPL, GCL, NFL), is reduced. Optomotor responses in dim conditions are impaired. Electroretinography shows completely absent b-wave response under dim conditions, and milder abnormalities under bright conditions (PubMed:24598786). Abolishes ON-responses and delays OFF-responses in retinal ganglion cells (PubMed:28334377). Rod photoreceptors show normal morphology (PubMed:28334377). Cone photoreceptor synapses show morphological abnormalities including a decrease in the number of triad processes in cone pedicles in favor of diad processes, the number of flat contacts at the base of pedicle synapses are increased, deep invaginating contacts made by cone ON-bipolar cells are lost, and vacuole-like structures are present at cone synaptic terminals (PubMed:28334377).|||dendrite http://togogenome.org/gene/10090:Upf2 ^@ http://purl.uniprot.org/uniprot/A2AT37 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Found in a post-splicing messenger ribonucleoprotein (mRNP) complex (By similarity). Associates with the exon junction complex (EJC) (By similarity). Interacts with SMG1, EST1A, UPF3A, UPF3B, EIF4A1 and EIF1 (By similarity). Interacts with UPF1; interaction is promoted by TDRD6 (PubMed:27149095). Interacts with DDX4 (PubMed:27149095).|||Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA.|||Knockout adult liver results in hepatosteatosis and disruption of liver homeostasis.|||Localized in male germ cells.|||Weakly expressed in neonatal testes and expression increases during the development of spermatocytes and spermatids, in the late meiotic and postmeiotic stages of spermatogenesis.|||perinuclear region http://togogenome.org/gene/10090:Cnst ^@ http://purl.uniprot.org/uniprot/Q8CBC4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNST family.|||Cell membrane|||Interacts with connexins GJA1/CX43, GJB1/CX32, GJB2/CX26, GJB3/CX31, GJB6/CX30 and GJC1/CX45. Also interacts with GGA1 and GGA2. Does not interact with PANX1.|||Required for targeting of connexins to the plasma membrane.|||secretory vesicle|||trans-Golgi network membrane http://togogenome.org/gene/10090:Pdlim3 ^@ http://purl.uniprot.org/uniprot/O70209 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ At 15 dpc highly expressed in skeletal muscle and heart.|||Interacts with ACTN2 (By similarity). Forms a heterodimer with PDLIM4 (via LIM domain) (PubMed:15663004).|||May play a role in the organization of actin filament arrays within muscle cells.|||Z line http://togogenome.org/gene/10090:F830016B08Rik ^@ http://purl.uniprot.org/uniprot/G3UWE2 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Rxra ^@ http://purl.uniprot.org/uniprot/A2AJP1|||http://purl.uniprot.org/uniprot/P28700|||http://purl.uniprot.org/uniprot/Q3UMU4|||http://purl.uniprot.org/uniprot/Q6LC96 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Composed of three domains: a modulating N-terminal or AF1 domain, a DNA-binding domain and a C-terminal ligand-binding or AF2 domain.|||Cytoplasm|||Down-regulated by infection with viruses, such as VSV, HSV-1 and MHV68 (PubMed:25417649). Down-regulated by aging (PubMed:26463675).|||Expressed in macrophages (at protein level).|||Homodimer (By similarity). Heterodimer with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity (PubMed:10882070). Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity (By similarity). Heterodimerizes with PPARG (PubMed:7838715). Heterodimerizes (via NR LBD) with RARB (By similarity). Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (By similarity). Interacts with coactivator NCO6 (PubMed:10788465). Interacts with coactivator NCO3 (By similarity). Interacts with coactivator FAM120B (PubMed:17595322). Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8 (By similarity). Interacts with PRMT2 (By similarity). Interacts with ASXL1 (PubMed:16606617). Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2 (By similarity). Interacts in a ligand-dependent fashion with MED1 and NCOA1 (PubMed:15528208, PubMed:16606617). Interacts with VDR (By similarity). Interacts with EP300; the interaction is decreased by 9-cis retinoic acid (By similarity). Heterodimer (via C-terminus) with NR4A1 (via DNA-binding domain); the interaction is enhanced by 9-cis retinoic acid (By similarity). NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).|||Homodimer. Heterodimer; with a rar molecule.|||Mitochondrion|||Nucleus|||Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain (PubMed:10383391, PubMed:12032153). Constitutively phosphorylated on Ser-22 in the presence or absence of ligand (PubMed:10383391, PubMed:12032153). Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265 (PubMed:10383391). Phosphorylated on Ser-28, in vitro, by PKA (By similarity). This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA (By similarity).|||Receptor for retinoic acid that acts as a transcription factor (PubMed:10383391, PubMed:12032153, PubMed:25417649). Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes (PubMed:1310259, PubMed:10383391). The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription (PubMed:1310259). The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid (PubMed:10383391, PubMed:25417649). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation (By similarity). Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA (PubMed:1310259). The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context (By similarity). The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes (By similarity). Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity). Acts as an enhancer of RARA binding to RARE DNA element (By similarity). May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1 (By similarity). Promotes myelin debris phagocytosis and remyelination by macrophages (PubMed:26463675). Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes (PubMed:25417649). Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence (By similarity).|||Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes.|||Reduced myelin debris uptake by bone marrow-derived macrophages (PubMed:26463675). Conditional knockout in myeloid cells results in reduced myelin debris clearing by macrophages, delayed oligodendrocyte progenitor cell differentiation and slowern remyelination after induced focal demyelination (PubMed:26463675).|||Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6. http://togogenome.org/gene/10090:Gm21209 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Tigd5 ^@ http://purl.uniprot.org/uniprot/Q499M4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tigger transposable element derived protein family.|||Nucleus http://togogenome.org/gene/10090:Shprh ^@ http://purl.uniprot.org/uniprot/Q7TPQ3 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||Broadly expressed (at protein level).|||E3 ubiquitin-protein ligase involved in DNA repair. Upon genotoxic stress, accepts ubiquitin from the UBE2N-UBE2V2 E2 complex and transfers it to 'Lys-164' of PCNA which had been monoubiquitinated by UBE2A/B-RAD18, promoting the formation of non-canonical poly-ubiquitin chains linked through 'Lys-63'.|||Homodimer. Interacts with HLTF, PCNA, UBE2N and RAD18.|||Probable cloning artifact.|||The RING finger mediates E3 ubiquitin ligase activity. http://togogenome.org/gene/10090:Or51a7 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFH3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Xrcc5 ^@ http://purl.uniprot.org/uniprot/P27641 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP3.|||Belongs to the ku80 family.|||Chromosome|||Expression increases during promyelocyte differentiation.|||Heterodimer composed of XRCC5/Ku80 and XRCC6/Ku70 (By similarity). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). Additional component of the NHEJ complex includes PAXX (By similarity). Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). The XRCC5-XRCC6 dimer also associates with NAA15, and this complex displays DNA binding activity towards the osteocalcin FGF response element (OCFRE) (By similarity). In addition, XRCC5 binds to the osteoblast-specific transcription factors MSX2 and RUNX2 (By similarity). Interacts with ELF3 (By similarity). Interacts with APLF (via KBM motif) (By similarity). The XRCC5/XRCC6 dimer associates in a DNA-dependent manner with APEX1 (By similarity). Identified in a complex with DEAF1 and XRCC6 (By similarity). Interacts with NR4A3; the DNA-dependent protein kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with RNF138 (By similarity). Interacts with CYREN (via KBM motif) (PubMed:30017584). Interacts with WRN (via KBM motif) (By similarity). Interacts (via N-terminus) with HSF1 (via N-terminus); this interaction is direct and prevents XRCC5/XRCC6 heterodimeric binding and non-homologous end joining (NHEJ) repair activities induced by ionizing radiation (IR) (By similarity). Interacts with DHX9; this interaction occurs in a RNA-dependent manner (By similarity). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA (By similarity). Interacts with ERCC6 (By similarity). Interacts with ATF7 (By similarity). The XRCC5-XRCC6 dimer associates with ALKBH2.|||Nucleus|||Phosphorylated on serine residues. Phosphorylation by PRKDC may enhance helicase activity.|||Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA. Required for double-strand break repair and V(D)J recombination. Also has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection. Binding to DNA may be mediated by XRCC6. The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription. In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome. Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.|||Sumoylated.|||The EEXXXDDL motif is required for the interaction with catalytic subunit PRKDC and its recruitment to sites of DNA damage.|||Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination following DNA damage, leading to its degradation and removal from DNA damage sites. Ubiquitinated by RNF138, leading to remove the Ku complex from DNA breaks.|||Up-regulation during myogenesis is inhibited by cAMP, 3-aminobenzamide and sodium butyrate. Expression in myoblasts is unaffected by X-rays and UV light.|||nucleolus http://togogenome.org/gene/10090:Strn ^@ http://purl.uniprot.org/uniprot/O55106 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat striatin family.|||Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein.|||Cytoplasm|||Interacts with protein phosphatase 2A (PP2A) (Potential). Interacts with CTTNBP2; this interaction may regulate dendritic spine distribution of STRN. Activation of glutamate receptors weakens the interaction with CTTNBP2 (By similarity).|||Mainly expressed in brain but is also expressed at low levels in various tissues such as kidney, spleen, skeletal muscle and lung.|||Membrane|||dendritic spine http://togogenome.org/gene/10090:Impa2 ^@ http://purl.uniprot.org/uniprot/Q3U3B7|||http://purl.uniprot.org/uniprot/Q91UZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inositol monophosphatase superfamily.|||Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain (By similarity).|||Cytoplasm|||Homodimer.|||Mostly expressed in brain, small intestine, heart, kidney, and spleen (at protein level). http://togogenome.org/gene/10090:Cdc25a ^@ http://purl.uniprot.org/uniprot/P48964 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the MPI phosphatase family.|||First detected at the blastocyst stage.|||Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14-3-3 epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage. Interacts with PIM1. Interacts with CHEK2; mediates CDC25A phosphorylation and degradation in response to infrared-induced DNA damages (By similarity). Interacts with HSP90AB1; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression (By similarity).|||Phosphorylated by CHEK1 on Ser-75, Ser-123, Ser-172, Ser-271, Ser-284 and Thr-497 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-123, Ser-271, and Ser-284 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-172 and Thr-497 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-75, Ser-123, Ser-172, Ser-271 and Ser-284 may also promote ubiquitin-dependent proteolysis of CDC25A by the SCF complex. Phosphorylation of CDC25A at Ser-75 by CHEK1 primes it for subsequent phosphorylation at Ser-75, Ser-81 and Ser-87 by NEK11. Phosphorylation by NEK11 is required for BTRC-mediated polyubiquitination and degradation. Phosphorylation by PIM1 leads to an increase in phosphatase activity. Phosphorylated by PLK3 following DNA damage, leading to promote its ubiquitination and degradation (By similarity).|||Stimulated by B-type cyclins. Stimulated by PIM1-mediated phosphorylation (By similarity).|||The phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated. Putative phosphorylation sites at Ser-78 and Ser-81 appear to be essential for this interaction (By similarity).|||Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin E, in vitro (By similarity). Phosphorylation by PIM1 leads to an increase in phosphatase activity (By similarity).|||Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase leading to its degradation by the proteasome. Ubiquitinated by a SCF complex containing BTRC and FBXW11 during S phase leading to its degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads to its stabilization (By similarity).|||Ubiquitously expressed in most developing tissue. High levels in the testis and lower levels in the ovary, particularly in germ cells. Lower levels also in kidney, liver, heart and muscle. http://togogenome.org/gene/10090:3110009E18Rik ^@ http://purl.uniprot.org/uniprot/Q9CRW3 ^@ Similarity ^@ Belongs to the UPF0538 family. http://togogenome.org/gene/10090:Srrd ^@ http://purl.uniprot.org/uniprot/Q8K2M3 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SRR1 family.|||Cytoplasm|||Plays a role in the regulation of heme biosynthesis and in the regulation of the expression of core clock genes.|||Up-regulated by hemin and 5-aminolevulinic acid. http://togogenome.org/gene/10090:Akr1c20 ^@ http://purl.uniprot.org/uniprot/Q8VC77|||http://purl.uniprot.org/uniprot/Q9CZU0 ^@ Similarity ^@ Belongs to the aldo/keto reductase family. http://togogenome.org/gene/10090:Adamts15 ^@ http://purl.uniprot.org/uniprot/P59384 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ At 10.5 dpc, strongly and specifically expressed in the developing heart tubes (PubMed:24220035). By 13.5 dpc, widely expressed including in the perichondrium in the developing autopod, brain, ear, whisker follicles, vertebral column and epidermis (PubMed:24220035). Also localizes to the myocardium of the developing right atrium, the bulbous cordis and the airway epithelia of the main bronchiole in the lung bud at 11.5 dpc, the vertebral column and dorsal root ganglia at 14.5 dpc, and the developing hind limb at 15.5 dpc (PubMed:24220035). In the adult colon, highly expressed in the muscularis externa (inner circular smooth muscle and outer longitudinal smooth muscle), muscularis mucosa, submucosal glands, crypt, villi epithelial cells, goblet cells and lamina propria (PubMed:24220035).|||Binds 1 zinc ion per subunit.|||Cell surface|||Glycosylated (PubMed:24220035). Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively (By similarity). Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL (By similarity). Fucosylation mediates the efficient secretion of ADAMTS family members (By similarity). Can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs (By similarity). Also N-glycosylated (PubMed:24220035). These other glycosylations can also facilitate secretion (By similarity).|||In embryonic skeletal muscle, significantly increased levels between 13.5 dpc and 15.5 dpc with maximal expression observed at 15.5 dpc (PubMed:23233679). Decreased levels in postnatal skeletal muscle (PubMed:23233679). In myoblasts, up-regulated soon after induction of myoblast differentiation (PubMed:23233679).|||Metalloprotease which has proteolytic activity against the proteoglycan VCAN, cleaving it at the 'Glu-1401-|-1402-Ala' site (PubMed:24220035). Cleaves VCAN in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion which is required for skeletal muscle development and regeneration (PubMed:23233679).|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Spin2g ^@ http://purl.uniprot.org/uniprot/A0A0N4SW15 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Cenpj ^@ http://purl.uniprot.org/uniprot/Q569L8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP10 family.|||Forms homodimers. Associates with microtubules plus ends; binds to beta-tubulin subunits exposed on microtubule outer surface at its distal tip; also associates with microtubule lattice. Associated with the gamma-tubulin complex. Interacts with the head domain of EPB41. Interacts with LYST. Interacts with CEP152 (via C-terminus). Interacts with STIL. Forms a complex with STIL and SASS6 (By similarity).|||Phosphorylation at Ser-577 and Ser-583 by PLK2 is required for procentriole formation and centriole elongation. Phosphorylation by PLK2 oscillates during the cell cycle: it increases at G1/S transition and decreases during the exit from mitosis. Phosphorylation at Ser-583 is also mediated by PLK4 but is not a critical step in PLK4 function in procentriole assembly.|||Plays an important role in cell division and centrosome function by participating in centriole duplication. Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles. Required for centriole elongation and for STIL-mediated centriole amplification. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner. May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (By similarity).|||centriole|||centrosome http://togogenome.org/gene/10090:Supt16 ^@ http://purl.uniprot.org/uniprot/G3X956|||http://purl.uniprot.org/uniprot/Q920B9 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated. ADP-ribosylation by PARP1 is induced by genotoxic stress and correlates with dissociation of FACT from chromatin.|||Although related to the peptidase M24 family, this protein lacks conserved active site residues suggesting that it may lack peptidase activity.|||Belongs to the peptidase M24 family. SPT16 subfamily.|||Chromosome|||Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II.|||Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II).|||Component of the FACT complex.|||Interacts with MYOG (via C-terminal region) (PubMed:23364797). Component of the FACT complex, a stable heterodimer of SSRP1 and SUPT16H. Also a component of a CK2-SPT16-SSRP1 complex which forms following UV irradiation, composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B. Interacts with NEK9. Binds to histone H2A-H2B. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Interacts with GTF2E2 (By similarity).|||Nucleus|||The C-terminal Glu-rich acidic region is essential for FACT activity.|||Widely expressed. Expressed in brain, liver, heart, kidneys, lungs, spleen, thymus, ovary, and testes, with highest levels of expression observed in thymus. http://togogenome.org/gene/10090:Flt3l ^@ http://purl.uniprot.org/uniprot/P49772 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Homodimer (soluble isoform).|||Secreted|||Stimulates the proliferation of early hematopoietic cells by activating FLT3. Synergizes well with a number of other colony stimulating factors and interleukins. http://togogenome.org/gene/10090:Or6c214 ^@ http://purl.uniprot.org/uniprot/Q8VGI9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ncf4 ^@ http://purl.uniprot.org/uniprot/P97369 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4 (By similarity). Interacts with NCF2 (PubMed:21551061). Interacts wirh NCF1 (By similarity). The NCF2-NCF4 complex interacts with GBP7 (via GB1/RHD3-type G domain) (PubMed:21551061).|||Component of the NADPH-oxidase, a multicomponent enzyme system responsible for the oxidative burst in which electrons are transported from NADPH to molecular oxygen, generating reactive oxidant intermediates. It may be important for the assembly and/or activation of the NADPH-oxidase complex.|||Endosome membrane|||Membrane|||The PB1 domain mediates the association with NCF2/p67-PHOX.|||The PX domain mediates interaction with membranes enriched in phosphatidylnositol 3-phosphate.|||cytosol http://togogenome.org/gene/10090:Tspan8 ^@ http://purl.uniprot.org/uniprot/Q8R3G9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||Membrane http://togogenome.org/gene/10090:Foxe3 ^@ http://purl.uniprot.org/uniprot/Q9QY14 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Defects in Foxe3 are the cause of the dysgenetic lens (dyl) phenotype. In mouse mutant dyl the lens vesicle fails to separate from the ectoderm, causing a fusion between the lens and the cornea. Lack of a proliferating anterior lens epithelium leads to absence of secondary lens fibers and a dysplastic, cataractous lens.|||Expressed in the developing lens from the start of lens placode induction and becomes restricted to the anterior proliferating cells when lens fiber differentiation begins.|||Expressed in the embryonic lens.|||Head ectoderm expression is induced by RAX and lens expression is induced by PAX6.|||Knockout mice are viable and fertile but show eye abnormalities; in some cases the eyes never open. Eyes are much smaller, the anterior chamber is not formed, and the pupil is markedly smaller. There are no abnormalities in brain development (PubMed:16199865). Mice show reduced smooth muscle cell (SMC) density and impaired SMC differentiation that is limited to the ascending aorta (PubMed:26854927).|||Nucleus|||Transcription factor that controls lens epithelial cell growth through regulation of proliferation, apoptosis and cell cycle (PubMed:10652278, PubMed:10890982). During lens development, controls the ratio of the lens fiber cells to the cells of the anterior lens epithelium by regulating the rate of proliferation and differentiation (PubMed:16199865). Controls lens vesicle closure and subsequent separation of the lens vesicle from ectoderm (PubMed:10652278). Is required for morphogenesis and differentiation of the anterior segment of the eye (PubMed:17064680). Controls the expression of DNAJB1 in a pathway that is crucial for the development of the anterior segment of the eye (By similarity). http://togogenome.org/gene/10090:Acap3 ^@ http://purl.uniprot.org/uniprot/Q6NXL5 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation ^@ Endosome membrane|||GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.|||GTPase-activating protein for the ADP ribosylation factor family.|||PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate protein binding to PIP2 or PIP3 containing membranes.|||The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions. http://togogenome.org/gene/10090:Or2g25 ^@ http://purl.uniprot.org/uniprot/L7N1Z1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ufc1 ^@ http://purl.uniprot.org/uniprot/Q9CR09 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family. UFC1 subfamily.|||E1-like enzyme which specifically catalyzes the second step in ufmylation. Accepts the ubiquitin-like modifier UFM1 from the E1 enzyme UBA5 and forms an intermediate with UFM1 via a thioester linkage. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.|||Interacts with UBA5 (via C-terminus). Interacts with UFL1. Interacts with KIRREL3. Interacts with UFM1. http://togogenome.org/gene/10090:Cav3 ^@ http://purl.uniprot.org/uniprot/P51637 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the caveolin family.|||Cell membrane|||Expressed predominantly in muscle.|||Golgi apparatus membrane|||Homooligomer. Interacts with DYSF. Interacts with DLG1 and KCNA5; forms a ternary complex. Interacts with DAG1 (via its C-terminal); the interaction prevents binding of DAG1 with DMD (By similarity). Interacts with TRIM72 (PubMed:19380584). Interacts with MUSK; may regulate MUSK signaling (PubMed:19940021). Interacts with BVES (PubMed:24066022). Interacts with CAVIN1, CAVIN2 and CAVIN4 (By similarity).|||May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. May also regulate voltage-gated potassium channels. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (PubMed:19380584). Mediates the recruitment of CAVIN2 and CAVIN3 proteins to the caveolae (By similarity).|||Sumoylation with SUMO3 by PIAS4 may reduce agonist-induced internalization and desensitization of adrenergic receptor ABRD2.|||caveola|||sarcolemma http://togogenome.org/gene/10090:Or6f1 ^@ http://purl.uniprot.org/uniprot/Q8VFP2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Btc ^@ http://purl.uniprot.org/uniprot/Q05928|||http://purl.uniprot.org/uniprot/Q3TP84|||http://purl.uniprot.org/uniprot/Q543J8 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Found in several mouse tissues including kidney, uterus and liver, as well as in beta tumor cell line and MCF-7 cells. It is not detected in the brain.|||Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members. Potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Monomer. Interacts with EGFR and ERBB4.|||extracellular space http://togogenome.org/gene/10090:Tspan18 ^@ http://purl.uniprot.org/uniprot/Q80WR1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc embryo expressed in the developing heart (PubMed:32694189). At 13.5 dpc embryo expressed in intersomatic vessel (PubMed:32694189).|||Belongs to the tetraspanin (TM4SF) family.|||Highly expressed in lung (PubMed:15489334). Expressed in adult heart, artery and vein (PubMed:32694189).|||Homozygote knockout mice lacking Tspan18 are viables.|||Interacts with ORAI1; this interaction regulates ORAI1 exit from the endoplasmic (ER), and/or Golgi, and trafficking to the cell surface.|||Membrane|||Plays a role in the cell surface localization of ORAI1 and may participate in the regulation of Ca(2+) signaling and the VWF release in response to inflammatory stimuli. http://togogenome.org/gene/10090:Elk3 ^@ http://purl.uniprot.org/uniprot/G3UVW8|||http://purl.uniprot.org/uniprot/G3UVX2|||http://purl.uniprot.org/uniprot/P41971 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Heart, liver, lung, kidney and muscle.|||Interacts with CTBP1.|||May be a negative regulator of transcription, but can activate transcription when coexpressed with Ras, Src or Mos. Forms a ternary complex with the serum response factor and the ETS and SRF motifs of the Fos serum response element.|||Nucleus http://togogenome.org/gene/10090:Or4a75 ^@ http://purl.uniprot.org/uniprot/A0A1L1SSZ5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r9 ^@ http://purl.uniprot.org/uniprot/K7N6Z8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zc3hav1 ^@ http://purl.uniprot.org/uniprot/D3Z5I1|||http://purl.uniprot.org/uniprot/Q3UPF5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs).|||Belongs to the ARTD/PARP family.|||Cytoplasm|||Homodimer or homooligomer. Homooligomerization is essential for its antiviral activity (By similarity). Interacts with EXOSC5 (By similarity). Interacts (via N-terminal domain) with DDX17 in an RNA-independent manner (By similarity). Interacts with EXOSC3, EXOSC7, DCP2 and DCP1A (By similarity). Interacts with PARN in an RNA-independent manner (By similarity). Interacts with XRN1 in an RNA-dependent manner (By similarity). Interacts (via N-terminal domain) with DHX30 (via N-terminus) in an RNA-independent manner (By similarity). Isoform 2 interacts (via zinc-fingers) with RIGI in an RNA-dependent manner (By similarity).|||Nucleus|||Phosphorylation at Ser-273 is essential for sequential phosphorylation of Ser-269, Ser-265, Ser-262 and Ser-257 by GSK3-beta. Phosphorylation by GSK3-beta enhances its antiviral activity (By similarity).|||The N-terminal domain is sufficient to bind to viral RNAs and promote their degradation. The second and fourth zinc fingers are involved in binding to specific viral RNAs. Contains a divergent PARP homology ADP-ribosyltransferase domain which lacks the structural requirements for NAD[+] binding. It is therefore inactive. http://togogenome.org/gene/10090:Tbce ^@ http://purl.uniprot.org/uniprot/Q8CIV8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBCE family.|||Cytoplasm|||Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state. Cofactors B and E can form a heterodimer which binds to alpha-tubulin and enhances their ability to dissociate tubulin heterodimers. Interacts with TBCD (By similarity).|||Tubulin-folding protein; involved in the second step of the tubulin folding pathway and in the regulation of tubulin heterodimer dissociation (PubMed:12389029, PubMed:17184771). Required for correct organization of microtubule cytoskeleton and mitotic splindle, and maintenance of the neuronal microtubule network (By similarity).|||Ubiquitously expressed.|||cytoskeleton http://togogenome.org/gene/10090:Fasn ^@ http://purl.uniprot.org/uniprot/P19096 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain.|||Homodimer which is arranged in a head to tail fashion (By similarity). Interacts with CEACAM1; this interaction is insulin and phosphorylation-dependent; reduces fatty-acid synthase activity (By similarity).|||Melanosome|||S-nitrosylation of Fatty acid synthase at cysteine residues Cys-1464 or Cys-2084 is important for the enzyme dimerization. In adipocytes, S-nitrosylation of Fatty acid synthase occurs under physiological conditions and gradually increases during adipogenesis.|||Up-regulated by endocannabinoid anandamide/AEA. http://togogenome.org/gene/10090:Or2n1b ^@ http://purl.uniprot.org/uniprot/Q8VG94 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem174 ^@ http://purl.uniprot.org/uniprot/Q9DCX7 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A previous study found the localization of TMEM174 in the endoplasmic reticulum (By similarity). A more recent study detected TMEM174 in cell membrane (By similarity). The difference between these two studies could be due to the use of different cell lines.|||Apical cell membrane|||Endoplasmic reticulum membrane|||Interacts with SLC34A1; regulates SLC34A1 internalization by PTH and FGF23.|||Kidney specific (PubMed:35459732, PubMed:35428804). Expressed in renal primary proximal tubule cells (PubMed:35428804).|||Regulator of plasma phosphate homeostasis. Decreases serum inorganic phosphate (Pi) uptake by regulating the sodium-phosphate cotransporter SLC34A1 trafficking by PTH and FGF23 in the kidney.|||Tmem174-deficient mice show markedly increased serum levels of Pi, FGF23, and PTH, resulting in vascular calcification. In addition, deficient mice exhibit reduced SLC34A1 responsiveness to FGF23 and PTH administration.|||Up-regulated by low-phosphate diet. http://togogenome.org/gene/10090:Edn2 ^@ http://purl.uniprot.org/uniprot/P22389 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the endothelin/sarafotoxin family.|||Secreted|||Vasoconstrictor. http://togogenome.org/gene/10090:Fgf20 ^@ http://purl.uniprot.org/uniprot/A0A7U3L6F4|||http://purl.uniprot.org/uniprot/Q9ESL9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Homodimer. Interacts with FGFR2 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Neurotrophic factor that regulates central nervous development and function.|||Secreted http://togogenome.org/gene/10090:Tas2r139 ^@ http://purl.uniprot.org/uniprot/Q7TQA5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Pex11g ^@ http://purl.uniprot.org/uniprot/Q6P6M5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxin-11 family.|||Expressed in liver and at much lower levels in heart, kidney and testis.|||Homodimer. Heterodimer with either PEX11A or PEX11B. Interacts with FIS1.|||Peroxisome membrane|||Promotes membrane protrusion and elongation on the peroxisomal surface. http://togogenome.org/gene/10090:Ankrd53 ^@ http://purl.uniprot.org/uniprot/Q3V0J4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with PSRC1; recruited by PSRC1 to the spindle during mitosis.|||Phosphorylated during mitosis.|||Required for normal progression through mitosis. Involved in chromosome alignment and cytokinesis via regulation of microtubules polymerization.|||spindle|||spindle pole http://togogenome.org/gene/10090:Pphln1 ^@ http://purl.uniprot.org/uniprot/Q8K2H1 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is probably required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3. In the HUSH complex, contributes to the maintenance of the complex at chromatin. Acts as a transcriptional corepressor and regulates the cell cycle, probably via the HUSH complex. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. May be involved in epithelial differentiation by contributing to epidermal integrity and barrier formation.|||Cytoplasm|||Embryonic lethality. Embryos die during early embryogenesis.|||Homodimer (By similarity). Component of the HUSH complex; at least composed of TASOR, PPHLN1 and MPHOSPH8 (By similarity). Interacts with SIN3A and HDAC1 (By similarity). May interact with PPL (By similarity).|||Nucleus|||Ubiquitously expressed. Strong expression in the developing somites and limbs, the embryonic nervous system and the adult brain. http://togogenome.org/gene/10090:Csn2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JF04|||http://purl.uniprot.org/uniprot/P10598|||http://purl.uniprot.org/uniprot/Q8BGL0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-casein family.|||Important role in determination of the surface properties of the casein micelles.|||Mammary gland specific. Secreted in milk.|||Secreted http://togogenome.org/gene/10090:Ubap2 ^@ http://purl.uniprot.org/uniprot/Q91VX2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Cytoplasm|||May interact with ANXA2.|||Nucleus|||Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage. May promote the degradation of ANXA2. http://togogenome.org/gene/10090:Krt40 ^@ http://purl.uniprot.org/uniprot/E9PV64|||http://purl.uniprot.org/uniprot/Q6IFX3 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||May play a role in late hair differentiation.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Gsk3b ^@ http://purl.uniprot.org/uniprot/E9QAQ5|||http://purl.uniprot.org/uniprot/Q5KU03|||http://purl.uniprot.org/uniprot/Q9WV60 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site (By similarity). Inhibited by IL22 treatment which also triggers phosphorylation at Ser-9, promoting inactivation (PubMed:24742671). Inhibited by lithium (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.|||Cell membrane|||Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:15791206, PubMed:22057101, PubMed:23395175). Requires primed phosphorylation of the majority of its substrates (PubMed:15791206, PubMed:22057101, PubMed:23395175). In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (By similarity). Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (By similarity). In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (By similarity). Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (By similarity). Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (By similarity). Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (By similarity). MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (By similarity). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (By similarity). Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (PubMed:21295697). Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (PubMed:10894547). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (PubMed:18288891). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (PubMed:16543145). Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:17391670). Phosphorylates MARK2, leading to inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (By similarity). Phosphorylates ZC3HAV1 which enhances its antiviral activity (By similarity). Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation (By similarity). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (By similarity). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation (By similarity). Regulates the circadian clock via phosphorylation of the major clock components including BMAL1, CLOCK and PER2 (PubMed:20049328, PubMed:28556462, PubMed:28903391, PubMed:20123978). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (By similarity). Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:20049328, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (PubMed:23542741). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity (By similarity). Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (By similarity). Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression (PubMed:28556462). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:22539723). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors (By similarity). Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B (By similarity). The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity (By similarity). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (PubMed:26240334, PubMed:29142209). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (PubMed:24742671).|||Cytoplasm|||Embryonic lethality at 16 dpc due to hepatocyte apoptosis.|||Expressed in the liver (at protein level).|||Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.|||Monomer (By similarity). Interacts with DAB2IP (via C2 domain); the interaction stimulates GSK3B kinase activation (By similarity). Interacts (via C2 domain) with PPP2CA (By similarity). Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1 (By similarity). Interacts with AXIN1; the interaction mediates hyperphosphorylation of CTNNB1 leading to its ubiquitination and destruction (PubMed:19141611). Interacts with and phosphorylates SNAI1 (By similarity). Interacts with DNM1L (via a C-terminal domain) (By similarity). Interacts with ARRB2 (PubMed:16051150). Interacts with DISC1 (PubMed:19303846). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with SGK3 (By similarity). Interacts with the CLOCK-BMAL1 heterodimer (By similarity). Interacts with ZBED3 (PubMed:19141611). Interacts with the BMAL1 (PubMed:20049328, PubMed:28903391). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (By similarity). Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (By similarity). Interacts with GSKIP (By similarity). Interacts with GID8 (By similarity). Interacts with PIWIL2 (PubMed:28903391). Interacts with LMBR1L (PubMed:31073040). Interacts with DDX3X (By similarity). Interacts with BIRC2 (By similarity). Interacts with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase activity (By similarity). Found in a complex with SLC39A6, SLC39A10 and with GSK3B that controls NCAM1 phosphorylation (PubMed:28098160).|||Nucleus|||Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and deactivates GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216. Phosphorylation of Ser-9 in the hippocampus peaks at CT0, whereas in the liver it peaks at CT12. Inactivated by phosphorylation at Ser-9 (By similarity). Phosphorylated in a circadian manner in the hippocampus (PubMed:28556462). http://togogenome.org/gene/10090:Epyc ^@ http://purl.uniprot.org/uniprot/P70186 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.|||Confined to the middle zone of embryonic epiphyseal cartilage consisting of flattened chondrocytes and the ossifying region in the limb buds of chick embryos. Has also been detected in testis.|||Expression starts at 12.5 dpc and is restricted to developing cartilage.|||May have a role in bone formation and also in establishing the ordered structure of cartilage through matrix organization.|||The O-linked polysaccharide on Ser-96 is probably the mucin type linked to GalNAc. There is one glycosaminoglycan chain, known to be dermatan sulfate, and it is probably the O-glycosylation at Ser-64.|||extracellular matrix http://togogenome.org/gene/10090:Rnf111 ^@ http://purl.uniprot.org/uniprot/Q99ML9 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Arkadia family.|||Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer.|||Cytoplasm|||E3 ubiquitin-protein ligase required for mesoderm patterning during embryonic development (PubMed:11298452). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP (PubMed:14657019). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (PubMed:14657019). In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors 'in use' are degraded (By similarity). Activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL (By similarity). Associates with UBE2D2 as an E2 enzyme (By similarity). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (PubMed:23530056). Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair (By similarity). Mediates ubiquitination and degradation of sumoylated PML (PubMed:23530056). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (PubMed:23530056).|||Mice rarely develop beyond 15 somites, have a reduced head, fail to undergo turning and die at midgestation.|||Monomer (By similarity). Interacts with SMAD6, SMAD7, AXIN1, AXIN2 and SKIL isoform SNON (PubMed:14657019). Interacts with (phosphorylated) SMAD2 and SMAD3 (PubMed:17341133). Part of a complex containing RNF111, AXIN1 and SMAD7 (By similarity). Interacts (via SIM domains) with SUMO1 and SUMO2 (PubMed:23530056).|||Nucleus|||PML body|||The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin. Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer.|||The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate.|||Ubiquitously expressed from ES cells to midgestation.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Lrch1 ^@ http://purl.uniprot.org/uniprot/P62046 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a negative regulator of GTPase CDC42 by sequestering CDC42-guanine exchange factor DOCK8. Probably by preventing CDC42 activation, negatively regulates CD4(+) T-cell migration in response to chemokine stimulation.|||Cytoplasm|||Interacts (via LRR repeats) with unphosphorylated DOCK8 (via DHR-2 domain); the interaction prevents the association between DOCK8 and CDC42.|||No visible phenotype. Mice are viable, fertile and have normal CD4(+) T-cell populations in lymph nodes and spleen. In an experimental autoimmune encephalomyelitis (EAE) disease model, the symptoms, such as paralysis, are more severe. http://togogenome.org/gene/10090:Agpat3 ^@ http://purl.uniprot.org/uniprot/Q9D517 ^@ Activity Regulation|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:15367102). Acts on LPA containing saturated or unsaturated fatty acids C16:0-C20:4 at the sn-1 position using C18:1, C20:4 or C18:2-CoA as the acyl donor (By similarity). Also acts on lysophosphatidylcholine, lysophosphatidylinositol and lysophosphatidylserine using C18:1 or C20:4-CoA (By similarity). Has a preference for arachidonoyl-CoA as a donor (PubMed:19114731). Has also a modest lysophosphatidylinositol acyltransferase (LPIAT) activity, converts lysophosphatidylinositol (LPI) into phosphatidylinositol (PubMed:19114731).|||Endoplasmic reticulum membrane|||In males, activity increases in an age-dependent fashion, maybe derived from the induction by sex-hormones.|||Nucleus envelope|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||Up-regulated in the heart by clofibrate, a PPAR-alpha agonist.|||Widely expressed. Mainly expressed in testis, kidney and liver (at protein level). http://togogenome.org/gene/10090:Tmem38b ^@ http://purl.uniprot.org/uniprot/Q9DAV9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM38 family.|||Endoplasmic reticulum membrane|||Homotrimer; trimerization probably requires binding to phosphatidylinositol 4,5-bisphosphate (PIP2).|||Mice are neonatal lethal. Mice lacking Tmem38a and Tmem38b show a weak heartbeat at E9.5 followed by loss of cardiomyocyte viability and embryonic lethality around 10.5 dpc.|||Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores.|||Widely expressed. http://togogenome.org/gene/10090:Clec1a ^@ http://purl.uniprot.org/uniprot/Q8BWY2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dcst1 ^@ http://purl.uniprot.org/uniprot/Q059Y8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||E3 ubiquitin-protein ligase which mediates 'Lys-48'-linked ubiquitination of STAT2 and induces its proteasomal degradation thereby negatively regulating type-I-interferon signaling.|||Essential sperm cell-surface protein required for sperm-egg fusion and fertilization.|||Expressed in testis.|||In testis, not detected before 3 weeks after birth.|||Interacts with STAT2; the interaction results in STAT2 'Lys-48'-linked ubiquitination leading to its proteasomal degradation. Interacts with DCST2 (PubMed:35393517).|||Knockout males are sterile despite normal mating behavior with ejaculation and vaginal plug formation (PubMed:33871360, PubMed:35393517). DCST1 and DCST2 double knockout males, but not females, are completely infertile. Mutants have no disturbances in sperm migration into the oviduct, acrosome reaction and zona penetration. Mutant spermatozoa are capable of binding to the plasma membranes of oocytes but fail to proceed to membrane fusion with oocytes (PubMed:33871360, PubMed:35393517).|||The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.|||acrosome membrane http://togogenome.org/gene/10090:Vmn1r116 ^@ http://purl.uniprot.org/uniprot/L7N2A6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stam2 ^@ http://purl.uniprot.org/uniprot/O88811|||http://purl.uniprot.org/uniprot/Q3TGH8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adult mice lacking Stam and Stam2 due to inducible gene targeting exhibit significant reduction in T-cell development in the thymus and profound reduction in the peripheral mature T-cells.|||Belongs to the STAM family.|||Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Part of a complex at least composed of HSG, STAM2 and EPS15. Interacts with JAK2 and JAK3. Interacts with ubiquitinated proteins and the deubiquitinating enzyme USP8/UBPY. Interacts (via the via the PxVxL motif) with CBX5; the interaction is direct. Interacts with VPS37C. Interacts with ubiquitin; the interaction is direct (By similarity). Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain).|||Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.|||Cytoplasm|||Early endosome membrane|||Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity).|||Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.|||Phosphorylated in response to IL-2, GM-CSF, EGF and PDGF.|||The SH3 domain mediates the interaction with USP8.|||The VHS and UIM domains mediate the interaction with ubiquitinated proteins.|||Ubiquitously expressed, with highest levels in testis. http://togogenome.org/gene/10090:Lmln ^@ http://purl.uniprot.org/uniprot/Q8BMN4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M8 family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Lipid droplet|||Metalloprotease. http://togogenome.org/gene/10090:Nt5el ^@ http://purl.uniprot.org/uniprot/Q9D3Z8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the 5'-nucleotidase family.|||Membrane http://togogenome.org/gene/10090:Pex3 ^@ http://purl.uniprot.org/uniprot/D3Z6X4|||http://purl.uniprot.org/uniprot/E9QA46|||http://purl.uniprot.org/uniprot/Q3UIG2|||http://purl.uniprot.org/uniprot/Q9QXY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxin-3 family.|||Identified in all tissues analyzed, with the strongest expression in liver and in testis.|||Interacts with PEX19.|||Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.|||Peroxisome membrane http://togogenome.org/gene/10090:Sval2 ^@ http://purl.uniprot.org/uniprot/Q99N75 ^@ Similarity|||Subunit ^@ Belongs to the PIP family.|||Monomer. Interacts with AZGP1. http://togogenome.org/gene/10090:Mrpl35 ^@ http://purl.uniprot.org/uniprot/Q9CQL6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the bacterial ribosomal protein bL35 family.|||Mitochondrion http://togogenome.org/gene/10090:Gm5168 ^@ http://purl.uniprot.org/uniprot/Q4KL04 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Nipal2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0G3|||http://purl.uniprot.org/uniprot/Q91WC7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NIPA family.|||Membrane http://togogenome.org/gene/10090:Wnt9b ^@ http://purl.uniprot.org/uniprot/O35468|||http://purl.uniprot.org/uniprot/Q2TBA6|||http://purl.uniprot.org/uniprot/Q8C718 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Wnt family.|||Complete perinatal lethality. All pups die within the first 24 hours after birth (PubMed:16054034). Mutant pups lack kidneys. In addition, females have normal ovaries, but no uterus. Males have testes, but lack the epididymis (PubMed:16054034). The early stages of the development of the ureteric component of the metanephric kidney appear normal, but branching after the T-stage is disrupted, and mutants lack mesonephric tubules at 11.5 dpc (PubMed:16054034). Mutant embryos have a cleft lip and palate phenotype at 18.5 dpc, plus additional, bilateral defects in upper jaw skeleton development (PubMed:16054034, PubMed:22461561). Embryos appear normal at 10.5 dpc, but display hypoplasia of the lateral and medial nasal process at 11 dpc. At 11.5 dpc, they display a clear bilateral gap between the medial nasal process and the fused medial end of the lateral nasal process and the maxillary process. The palatal shelves display lack of midline contact at 14.5 dpc.|||Detected throughout the Wolffian duct epithelium from 9.5 dpc to 14.5 dpc. Detected in the stalk region of the ureteric bud at 10.5 to 11.0 dpc. Continues to be expressed in the developing collecting duct system throughout nephrogenesis, but is not detected at branching tips. Within the urogenital tract, expression is restricted to the kidney at 15.5 dpc (PubMed:16054034). Detected in embryonic head from early headfold stages to at least 12 dpc.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids. Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly in the complex with LRP6. Interacts with PKD1 (via extracellular domain).|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:22461561, PubMed:16054034, PubMed:17537789). Required for normal embryonic kidney development, and for normal development of the urogenital tract, including uterus and part of the oviduct and the upper vagina in females, and epididymis and vas deferens in males (PubMed:16054034). Activates a signaling cascade in the metanephric mesenchyme that induces tubulogenesis (PubMed:16054034, PubMed:17537789). Acts upstream of WNT4 in the signaling pathways that mediate development of kidney tubules and the Muellerian ducts (PubMed:16054034). Plays a role in cranofacial development and is required for normal fusion of the palate during embryonic development (PubMed:16054034, PubMed:22461561, PubMed:25257647).|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||Spontaneous insertion of a retrotransposon in the Wnt9b promoter region causes reduced Wnt9b expression. Decreased Wnt9b expression is correlated with increased incidence of cleft lip and palate.|||extracellular matrix http://togogenome.org/gene/10090:Snrpd1 ^@ http://purl.uniprot.org/uniprot/P62315 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP core protein family.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts (via C-terminus) with SMN1 (via Tudor domain); the interaction is direct. Interacts with GEMIN2; the interaction is direct. Interacts with SNRPD2; the interaction is direct.|||Methylated on arginine residues by PRMT5 and PRMT7; probable asymmetric dimethylation which is required for assembly and biogenesis of snRNPs.|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through non-specific electrostatic contacts with RNA.|||cytosol http://togogenome.org/gene/10090:Mrpl15 ^@ http://purl.uniprot.org/uniprot/Q9CPR5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL15 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Mup21 ^@ http://purl.uniprot.org/uniprot/Q80YX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Exoc7 ^@ http://purl.uniprot.org/uniprot/A2AAN0|||http://purl.uniprot.org/uniprot/O35250|||http://purl.uniprot.org/uniprot/Q3USE0|||http://purl.uniprot.org/uniprot/Q542L0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EXO70 family.|||Cell membrane|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. In adipocytes, plays a crucial role in targeting SLC2A4 vesicle to the plasma membrane in response to insulin, perhaps directing the vesicle to the precise site of fusion. It is required for neuron survival and plays an essential role in cortical development (By similarity).|||Midbody ring|||The C-terminus is required for translocation to the plasma membrane.|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8. Interacts with RAB11FIP3 (By similarity). Interacts with ARHQ in a GTP-dependent manner.|||cytosol http://togogenome.org/gene/10090:Prpf18 ^@ http://purl.uniprot.org/uniprot/Q8BM39 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRP18 family.|||Heterodimer with PPIH. Interacts with PRPF4 and with the spliceosome. Part of a complex containing U4/U6 snRNPs (By similarity).|||Intron retention.|||May be due to an intron retention.|||Nucleus speckle|||Participates in the second step of pre-mRNA splicing. http://togogenome.org/gene/10090:Adgre4 ^@ http://purl.uniprot.org/uniprot/Q91ZE5 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Forms a heterodimer, consisting of a large extracellular region (alpha subunit) non-covalently linked to a seven-transmembrane moiety (beta subunit).|||Glycosylated.|||May mediate the cellular interaction between myeloid cells and B-cells.|||Predominantly expressed in myeloid cells. Predominantly expressed on resident macrophages.|||Proteolytically cleaved into 2 subunits, an extracellular alpha subunit and a seven-transmembrane subunit.|||The second EGF domain mediates the interaction with the putative ligand.|||Up-regulated following macrophage activation. http://togogenome.org/gene/10090:Insig1 ^@ http://purl.uniprot.org/uniprot/Q8BGI3 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the INSIG family.|||Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4.|||Endoplasmic reticulum membrane|||Interacts with SCAP; interaction is direct and only takes place in the presence of sterols; it prevents interaction between SCAP and the coat protein complex II (COPII). Associates with the SCAP-SREBP complex (composed of SCAP and SREBF1/SREBP1 or SREBF2/SREBP2); association is mediated via its interaction with SCAP and only takes place in the presence of sterols. Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway. Interacts with SOAT2/ACAT2; leading to promote recruitment of AMFR/gp78 and subsequent ubiquitination of SOAT2/ACAT2. Interacts with RNF139. Interacts with RNF145.|||Knockout mice with a conditional deletion of Insig1 in the liver and a germline deletion of Insig2 overaccumulate cholesterol and triglycerides in liver: despite this accumulation, levels of nuclear sterol regulatory element-binding proteins (SREBPs) are not reduced (PubMed:16100574). The amount of HMGCR is also elevated, caused by impaired degradation of the enzyme (PubMed:16100574). Knockout mice with a germline deletion of both Insig1 and Insig2 die within one day of birth (PubMed:16100574, PubMed:16955138). After 18.5 days of development, embryos lacking both Insig1 and Insig2 show defects in midline facial development, ranging from cleft palate to complete cleft face: middle and inner ear structures are abnormal, but teeth and skeletons are normal (PubMed:16955138). The livers and heads of embryos lacking both Insig1 and Insig2 overproduce sterols, causing a marked buildup of sterol intermediates (PubMed:16955138).|||Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:16100574). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (By similarity). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:16100574). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (By similarity). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG1 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (By similarity). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligases AMFR/gp78 and/or RNF139 (By similarity). Also regulates degradation of SOAT2/ACAT2 when the lipid levels are low: initiates the ubiquitin-mediated degradation of SOAT2/ACAT2 via recruitment of the ubiquitin ligases AMFR/gp78 (By similarity).|||Phosphorylation at Ser-189 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG1 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes.|||The KxHxx motif mediates association with the coatomer complex.|||Ubiquitinated by AMFR/gp78 in response to sterol deprivation, leading to its degradation: when the SCAP-SREBP complex becomes dissociated from INSIG1, INSIG1 is then ubiquitinated and degraded in proteasomes. Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex. Ubiquitinated by RNF139.|||Up-regulated progressively in the fat tissue as they develop diet-induced obesity (PubMed:12869692). Up-regulated in differentiating preadipocytes (PubMed:12869692). http://togogenome.org/gene/10090:Zc3h8 ^@ http://purl.uniprot.org/uniprot/Q9JJ48 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. Acts as a transcriptional repressor of the GATA3 promoter. Induces thymocyte apoptosis when overexpressed, which may indicate a role in regulation of thymocyte homeostasis (By similarity). Sequence-specific DNA-binding factor that binds to the 5'-AGGTCTC-3' sequence within the negative cis-acting element intronic regulatory region (IRR) of the GATA3 gene.|||Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts with ICE1 (via C-terminus domain) (By similarity).|||Highly expressed in heart, muscle, testis, kidney, brain, liver, lung and spleen.|||Nucleus|||The N-terminal region and all three C3H1-type zinc fingers are necessary to induce transcriptional repression. http://togogenome.org/gene/10090:Psme2b ^@ http://purl.uniprot.org/uniprot/P97372|||http://purl.uniprot.org/uniprot/Q5SVP3 ^@ Function|||Induction|||Similarity|||Subunit ^@ Belongs to the PA28 family.|||By interferon gamma.|||Heterodimer of PSME1 and PSME2, which forms a hexameric ring.|||Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. http://togogenome.org/gene/10090:Tmco1 ^@ http://purl.uniprot.org/uniprot/Q3V4A0|||http://purl.uniprot.org/uniprot/Q921L3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMCO1 family.|||Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (PubMed:27212239). In response to endoplasmic reticulum (ER) overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (PubMed:27212239). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (By similarity). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity). Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (By similarity).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer and homotetramer. Homodimer under resting conditions; forms homotetramers following and ER calcium overload. Component of the GET- and EMC-like (GEL) complex, composed of RAB5IF/OPTI and TMCO1. The GEL complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.|||Membrane|||Mice are born at a much lower rate than predicted by the Mendelian ratio. Surviving mice show a reduced body size, low survival rate and delayed osteogenesis. Adult mice display craniofacial dysmorphism such as open cranial sutures, flattened faces with shorten nasal bones and skull anomalies. Moreover, magnetic resonance imaging (MRI) of brain shows significantly enlarged brain ventricles. Adult mice show defects in spatial recognition memory in a Y-maze task assay and a significant deficiency in motor coordination in rotarod assessments. Defects are probably due to calcium overload, calcium imaging results revealing a significant overload of endoplasmic reticulum calcium in osteoblasts. http://togogenome.org/gene/10090:Kazald1 ^@ http://purl.uniprot.org/uniprot/Q8BJ66 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ At 15 dpc embryos, weakly expressed in osteoblasts within the distal area of the ossification center of the mid-shaft region of the ulna and the radius. At 16 dpc embryos highly expressed in mandible, maxilla, frontal bone and ossification regions of the nasal septum. At 17 dpc embryos expression is localized to developing mandibular and maxillar bones, the frontal bones and in the nasal capsule surrounding the nasopharynx. Expression throughout the developing mandibular bone is found in 15 dpc-17 dpc embryos. Present in periosteum of the humerus at 16.5 dpc (at protein level).|||Highly expressed in the spleen. Moderately expressed in the skin, lung and urinary bladder. Weakly expressed in the brain, tongue, esophagus, stomach, large intestine, liver and bone. Expressed in osteoblastic cells during bone regeneration. Expressed in secretory osteoblasts in the tooth.|||Involved in the proliferation of osteoblasts during bone formation and bone regeneration. Promotes matrix assembly.|||Up-regulated during the early phase of the bone regeneration. Up-regulated by BMP2 during osteoblast differentiation.|||extracellular matrix http://togogenome.org/gene/10090:Ripor3 ^@ http://purl.uniprot.org/uniprot/A1L3T7 ^@ Similarity ^@ Belongs to the RIPOR family. http://togogenome.org/gene/10090:Polr3d ^@ http://purl.uniprot.org/uniprot/Q91WD1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPC4/POLR3D RNA polymerase subunit family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. Interacts with POLR3E/RPC5 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or8k1 ^@ http://purl.uniprot.org/uniprot/Q7TR79 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam241a ^@ http://purl.uniprot.org/uniprot/Q9CZL2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM241 family.|||Membrane http://togogenome.org/gene/10090:Adad1 ^@ http://purl.uniprot.org/uniprot/Q5SUE7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ADAD family.|||Mice exhibit spermatozoa retention in stage IX tubules and a reduction in the number of sperm in the epididymis, leading to a reduction in fertility (PubMed:15649457). Show defects in germ-cell development (PubMed:32665638).|||Nucleus|||Required for male fertility and normal male germ cell differentiation (PubMed:32665638). Plays a role in spermatogenesis (PubMed:15649457). Binds to RNA but not to DNA (PubMed:15649457).|||Testis-specific. Detected in round spermatid cells from stage II-XI (at protein level). Expressed in germ cells from mid-pachytene spermatocytes to mid-round spermatids. http://togogenome.org/gene/10090:Fbxl19 ^@ http://purl.uniprot.org/uniprot/Q6PB97 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subunit ^@ Acetylated by CREBBP; leading to ubiquitination and subsequent proteasomal degradation.|||Deletion of the CXXC zinc finger domain of FBXL19 leads to mouse embryonic lethality.|||Directly interacts with SKP1 and CUL1. Interacts with RNF20 (PubMed:28453857).|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that plays a role in different processes including cell migration, cell proliferation or cytoskeletal reorganization (PubMed:28453857, PubMed:29809150). Mediates RHOA ubiquitination and degradation in a ERK2-dependent manner. Induces RAC1 and RAC3 degradation by the proteasome system and thereby regulates TGFB1-induced E-cadherin down-regulation and cell migration. Mediates also ubiquitination and degradation of IL-33-induced receptor IL1RL1 and subsequently blocks IL-33-mediated apoptosis (PubMed:22660580). Within the nucleus, binds to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides (PubMed:28453857, PubMed:29809150). Recruits CDK-mediator to chromatin and targets CDK8 to promoters of silent developmental genes leading to induction of these genes during cell differentiation (PubMed:29809150). In addition, plays a critical role in the recruitment of RNF20 to histone H2B leading to H2B mono-ubiquitination (PubMed:28453857).|||The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. http://togogenome.org/gene/10090:Col17a1 ^@ http://purl.uniprot.org/uniprot/Q07563 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homotrimers of alpha 1(XVII)chains. Interacts (via cytoplasmic region) with ITGB4 (via cytoplasmic region). Interacts (via cytoplasmic region) with DST (via N-terminus). Interacts (via N-terminus) with PLEC. Interacts (via cytoplasmic region) with DSP (By similarity).|||May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.|||Membrane|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The 120 kDa linear IgA disease antigen homolog is an anchoring filament component involved in dermal-epidermal cohesion.|||The ectodomain is shedded from the surface of keratinocytes resulting in a 120-kDa soluble form, also named as 120 kDa linear IgA disease antigen homolog. The shedding is mediated by membrane-bound metalloproteases. This cleavage is inhibited by phosphorylation at Ser-551 (By similarity).|||The intracellular/endo domain is disulfide-linked.|||basement membrane|||hemidesmosome http://togogenome.org/gene/10090:Cd274 ^@ http://purl.uniprot.org/uniprot/Q9EP73 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Cell membrane|||Early endosome membrane|||Highly expressed in the heart, thymus, skeletal muscle, and lung. Weakly expressed in the kidney, spleen, thyroid, and liver. Expressed on activated dendritic cells, B-cells and macrophages. Expressed in numerous tumor cells lines of lymphoid origin.|||Interacts with PDCD1 (PubMed:11015443). Interacts with CMTM4 and CMTM6 (By similarity).|||Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11238124). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11238124). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:11015443, PubMed:12719480).|||Recycling endosome membrane|||The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:12218188, PubMed:27281199). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (PubMed:12218188). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (PubMed:12218188).|||Ubiquitinated; STUB1 likely mediates polyubiquitination of PD-L1/CD274 triggering its degradation. Ubiquitinated by MARCHF8; leading to degradation.|||Up-regulated by IFNG treatment in monocytes. Up-regulated on dendritic cells, B-cells and macrophages after activation by LPS and IFNG. http://togogenome.org/gene/10090:Eif3b ^@ http://purl.uniprot.org/uniprot/Q8JZQ9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eIF-3 subunit B family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Also interacts with UPF2 and HNRPD. Interacts with METTL3. Interacts with DDX3X (By similarity).|||Cytoplasm|||Embryonic death.|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation.|||RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Stress granule|||The RRM domain mediates interaction with EIF3J.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Igfbp4 ^@ http://purl.uniprot.org/uniprot/P47879 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds IGF2 more than IGF1.|||IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.|||Secreted http://togogenome.org/gene/10090:Itga2 ^@ http://purl.uniprot.org/uniprot/Q62469 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. Alpha-2 associates with beta-1. Interacts with HPS5 and RAB21.|||Integrin alpha-2/beta-1 is a collagen receptor, being responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. It is also a receptor for laminins, collagen C-propeptides and E-cadherin. Mice homozygous for a null mutation in the alpha-2 die very early in embryogenesis.|||Membrane|||The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. http://togogenome.org/gene/10090:Rab9 ^@ http://purl.uniprot.org/uniprot/Q0PD48|||http://purl.uniprot.org/uniprot/Q9R0M6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts (preferentially in its GTP-bound form) with GCC2 (via its GRIP domain) (By similarity). Interacts (GTP-bound form) with SGSM1; the GDP-bound form has much lower affinity for SGSM1 (PubMed:25220469). Interacts with SGSM2 (PubMed:26620560). The GTP-bound form but not the GDP-bound form interacts with HPS4 (PubMed:26620560, PubMed:20048159). The GTP-bound form but not the GDP-bound form interacts with BLOC-3 complex (heterodimer of HPS1 and HPS4) but does not interact with HPS1 alone (By similarity).|||Involved in the transport of proteins between the endosomes and the trans-Golgi network (By similarity). Involved in the recruitment of SGSM2 to melanosomes and is required for the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (PubMed:26620560).|||Late endosome|||Melanosome|||Membrane|||phagosome|||phagosome membrane http://togogenome.org/gene/10090:Rp2 ^@ http://purl.uniprot.org/uniprot/Q9EPK2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a GTPase-activating protein (GAP) involved in trafficking between the Golgi and the ciliary membrane. Involved in localization of proteins, such as NPHP3, to the cilium membrane by inducing hydrolysis of GTP ARL3, leading to the release of UNC119 (or UNC119B). Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization. Acts as guanine nucleotide dissociation inhibitor towards ADP-ribosylation factor-like proteins.|||Belongs to the TBCC family.|||Cell membrane|||Found in a complex with ARL3, RP2 and UNC119 (or UNC119B); RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119 (or UNC119B). Interacts with ARL3; interaction is direct and stimulated with the activated GTP-bound form of ARL3 (By similarity).|||Myristoylated on Gly-2; which may be required for membrane targeting.|||Palmitoylated on Cys-3; which may be required for plasma membrane targeting.|||Retina (at protein level).|||cilium http://togogenome.org/gene/10090:Dhx57 ^@ http://purl.uniprot.org/uniprot/Q6P5D3 ^@ Function|||Similarity ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Probable ATP-binding RNA helicase. http://togogenome.org/gene/10090:Fam78b ^@ http://purl.uniprot.org/uniprot/Q8BQN5 ^@ Similarity ^@ Belongs to the FAM78 family. http://togogenome.org/gene/10090:Rec114 ^@ http://purl.uniprot.org/uniprot/Q9CWH4 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the REC114 family.|||Expressed in adult testis and embryonic ovary. Also expressed at low levels in liver.|||In the testis, expression is detected at 4 days postpartum (dpp) with a peak at day 10. Levels decrease between 14-18 dpp with an increase in the adult.|||Interacts with MEI4 (PubMed:20551173). Interacts with IHO1 (PubMed:27723721). Part of the MCD recombinosome complex, at least composed of IHO1, REC114 and MEI4 (PubMed:27723721). Interacts with ANKRD31; the interaction is direct (PubMed:31000436, PubMed:31003867).|||Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination (PubMed:20551173, PubMed:27723721). Probably acts by forming a complex with IHO1 and MEI4, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis (PubMed:27723721). http://togogenome.org/gene/10090:Rnf126 ^@ http://purl.uniprot.org/uniprot/Q91YL2 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in B-cells (at protein level).|||E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins (By similarity). Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates (PubMed:23418353). Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome (By similarity). Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome (By similarity). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (By similarity). May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination (PubMed:23418353). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (By similarity). May monoubiquitinate AICDA (By similarity).|||Interacts with CCDC50, EGFR, FLT3 and SCAMP3 (PubMed:23418353). Interacts with BAG6 (via ubiquitin-like domain); required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol (By similarity). Interacts with CDKN1A (By similarity). Interacts with AICDA (By similarity).|||Nucleus|||The C4-type zinc finger is required for interaction with BAG6.|||Ubiquitinated. May undergo autoubiquitination.|||Up-regulated in B-cells that undergo class-switch recombination (at protein level). http://togogenome.org/gene/10090:Rp1 ^@ http://purl.uniprot.org/uniprot/P56716 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As early as postnatal day 7, mice have already undergone significant molecular retinal changes. The molecular responses change dramatically during development and were distinct from responses to the disruption of the photoreceptor transcription factors Crx, Pde6b and Nrl. The JNK signaling cascades are specifically compromised in Rp1 defective retinas. Double heterozygotes of Rp1 and Rp1l1 exhibit abnormal outer segment morphology and reduced single rod photosensitivity and dark currents.|||Expressed in the cell bodies and inner segments of photoreceptors. Not found in liver, spleen, kidney, brain, thymus, muscle, heart, lung and testis.|||Gene expression is stimulated by retinal hypoxia and suppressed by relative retinal hyperoxia.|||Interacts (via the doublecortin domains) with microtubules. Interacts with RP1L1. Interacts with MAK.|||Microtubule-associated protein regulating the stability and length of the microtubule-based axoneme of photoreceptors. Required for the differentiation of photoreceptor cells, it plays a role in the organization of the outer segment of rod and cone photoreceptors ensuring the correct orientation and higher-order stacking of outer segment disks along the photoreceptor axoneme.|||The doublecortin domains, which mediate interaction with microtubules, are required for regulation of microtubule polymerization and function in photoreceptor differentiation.|||cilium axoneme|||photoreceptor outer segment http://togogenome.org/gene/10090:Hgfac ^@ http://purl.uniprot.org/uniprot/Q545J3|||http://purl.uniprot.org/uniprot/Q9R098 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activates hepatocyte growth factor (HGF) by converting it from a single chain to a heterodimeric form.|||Belongs to the peptidase S1 family.|||Heterodimer of a short chain and a long chain linked by a disulfide bond.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Zik1 ^@ http://purl.uniprot.org/uniprot/Q80YP6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in ovary and liver, and at lower levels in brain and muscle.|||Interacts with HNRPK.|||May be a transcriptional repressor.|||Nucleus http://togogenome.org/gene/10090:Tlr5 ^@ http://purl.uniprot.org/uniprot/A0A0A6YVY4|||http://purl.uniprot.org/uniprot/Q05AH3|||http://purl.uniprot.org/uniprot/Q8CB40|||http://purl.uniprot.org/uniprot/Q9JLF7 ^@ Disruption Phenotype|||Function|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Toll-like receptor family.|||Deficient mice exhibit a markedly altered enteric microbiota composition, with increased levels of fecal flagellin.|||Highly expressed in liver (PubMed:30089902). Detected in lung and at very low levels in most other tissues.|||Homodimer. Interacts with MYD88 (via TIR domain). Interacts with TICAM1 (via TIR domain). Interacts with UNC93B1; this interaction is essential for proper TLR5 localization to the plasma membrane.|||Membrane|||Pattern recognition receptor (PRR) located on the cell surface that participates in the activation of innate immunity and inflammatory response. Recognizes small molecular motifs named pathogen-associated molecular pattern (PAMPs) expressed by pathogens and microbe-associated molecular patterns (MAMPs) usually expressed by resident microbiota. Upon ligand binding such as bacterial flagellins, recruits intracellular adapter proteins MYD88 and TRIF leading to NF-kappa-B activation, cytokine secretion and induction of the inflammatory response. Plays thereby an important role in the relationship between the intestinal epithelium and enteric microbes and contributes to the gut microbiota composition throughout life.|||Phosphorylated at Tyr-799 upon flagellin binding; required for signaling.|||The TLR5 gene lies in a locus that is associated with susceptibility to Salmonella. Inbred strains of mice can be classified into 3 categories according to their resistance to infection with S.typhimurium: susceptible (BALB/c, C57BL/6, C3H/He), intermediate (DBA/2, C75L) and resistant (A, CBA). The strain MOLF/Ei is highly susceptible to the infection, has an unique TLR5 haplotype and a lower expression of TRL5. http://togogenome.org/gene/10090:Nsun7 ^@ http://purl.uniprot.org/uniprot/A0A0J9YV71|||http://purl.uniprot.org/uniprot/E9QPI2|||http://purl.uniprot.org/uniprot/Q14AW5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.|||Expressed in testis.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Low expression in 12-day-old testes when the majority of advanced cells are in zygonema, but increased by 14 to 18 days of age when most spermatocytes are in pachynema.|||Male infertility. A mutation which results in the conversion of codon 333, encoding glutamine, into a premature stop codon is detected in chemically-induced mutant Ste5Jcs1 mice; these mice are characterized by sperm motility defects and infertility.|||May have S-adenosyl-L-methionine-dependent methyl-transferase activity. http://togogenome.org/gene/10090:Or6y1 ^@ http://purl.uniprot.org/uniprot/E9Q050 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wdr35 ^@ http://purl.uniprot.org/uniprot/Q8BND3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis and ciliary protein trafficking (PubMed:21473986). May promote CASP3 activation and TNF-stimulated apoptosis (By similarity).|||Component of the IFT complex A (IFT-A) complex. IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts directy with IFT122, ITF43 and TTC21B. Interacts with IFT43.|||centrosome|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Gpbp1 ^@ http://purl.uniprot.org/uniprot/Q6NXH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the vasculin family.|||Functions as a GC-rich promoter-specific transactivating transcription factor.|||Interacts with GTF2B, GTF2F2, RNA polymerase II and TBP.|||Nucleus|||Ubiquitously expressed (at protein level). http://togogenome.org/gene/10090:Osbpl7 ^@ http://purl.uniprot.org/uniprot/Q3TAX1 ^@ Similarity ^@ Belongs to the OSBP family. http://togogenome.org/gene/10090:Or13p10 ^@ http://purl.uniprot.org/uniprot/L7MU75 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Donson ^@ http://purl.uniprot.org/uniprot/Q9QXP4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 14.5 dpc, widely expressed, including in neocortex, cerebellum, lung, liver, hindlimb, intestine, as well as forelimb, kidney and spinal cord vertebrae.|||Belongs to the DONSON family.|||Component of the replisome complex composed of at least MCM2, MCM7, PCNA and TICRR; interaction at least with PCNA occurs during DNA replication.|||Early embryonic lethality. Heterozygous mice show no overt phenotype.|||Nucleus|||Replisome component that maintains genome stability by protecting stalled or damaged replication forks. After the induction of replication stress, required for the stabilization of stalled replication forks, the efficient activation of the intra-S-phase and G/2M cell-cycle checkpoints and the maintenance of genome stability. http://togogenome.org/gene/10090:Cox4i1 ^@ http://purl.uniprot.org/uniprot/A2RSV8|||http://purl.uniprot.org/uniprot/P19783 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase IV family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Interacts with PHB2; the interaction decreases in absence of SPHK2 (PubMed:20959514). Interacts with AFG1L (By similarity). Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding.|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Bcas3 ^@ http://purl.uniprot.org/uniprot/Q8CCN5 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Rudhira' stands for 'blood' in Sanskrit as this protein is strongly expressed in blood vessels.|||Belongs to the BCAS3 family.|||Cytoplasm|||Due to an intron retention.|||Expressed in blood islands and yolk sac blood islands (at protein level). Highly expressed in mammary tumors. Expressed in eostrogen-induced epithelial cells of mammary glands. Expressed in brain, heart, kidney, lung, liver and spleen. Expressed in embryonic stem cells, embryoid bodies, endothelial cells and fibroblasts.|||Expressed in erythroid cells in the vessels at 9.5 and 10.5 dpc (at protein level). Expressed in embryo at 7.5 dpc and in the yolk sac at 10.5 dpc. Expressed in the heart and yolk sac mesoderm at 8.5 dpc. Expressed in the head mesenchyme, somitic mesoderm, otic vesicle, vessels and few blood cells at 9.5 to 11.5 dpc.|||Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin (By similarity). Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy. Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures (By similarity).|||Has been proposed to contain 7 WD repeats. This prediction could not be reproduced.|||Interacts with histone H3, ESR1, KAT2B and PELP1; the interactions occur in a estrogen-dependent manner. Interacts with beta-tubulin and VIM. Interacts (via C-terminal) with PHAF1; the interaction is requrired for the association with the phagophore (By similarity).|||Nucleus|||Preautophagosomal structure|||Up-regulated by PELP1 in response to estrogen.|||cytoskeleton http://togogenome.org/gene/10090:Slc9b2 ^@ http://purl.uniprot.org/uniprot/Q5BKR2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically inhibited by the N-terminal domain. Inhibited by phloretin.|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Electroneutral Na(+) Li(+)/H(+) antiporter that extrudes Na(+) or Li(+) in exchange for external protons across the membrane (PubMed:18508966, PubMed:17988971). Uses the proton gradient/membrane potential to extrude sodium (By similarity). Contributes to the regulation of intracellular pH and sodium homeostasis (PubMed:27909897). Also able to mediate Na(+)/Li(+) antiporter activity in kidney (By similarity). May play a physiological role in renal tubular function and blood pressure homeostasis (PubMed:32956652, PubMed:27909897). Plays an important role for insulin secretion and clathrin-mediated endocytosis in beta-cells (PubMed:23720317). Involved in sperm motility and fertility (PubMed:27010853). It is controversial whether SLC9B2 plays a role in osteoclast differentiation or not (PubMed:20441802, PubMed:17988971).|||Endosome membrane|||Homodimer; dimerization is essential for SLC9B2 activity. Lipids seem to play a role in the stabilization of the dimerization subdomain.|||Inhibited by phloretin but not by the classical SLC9A-inhibitor amiloride.|||Lysosome membrane|||Mitochondrion membrane|||No visible phenotype. However males show reduced fertility caused by diminished sperm motility (PubMed:27010853). Deficient mice display a pathological glucose tolerance with impaired insulin secretion but normal peripheral insulin sensitivity (PubMed:23720317). Mutant have normal bone density and their bones are characterized by normal structural parameters (PubMed:20441802, PubMed:22985540).|||Not detectable during the early stages of osteoclast differentiation induced by TNFSF11/RANKL (PubMed:17698421, PubMed:17988971). Up-regulated during the later stages of osteoclast differentiation (PubMed:20441802, PubMed:18508966, PubMed:17698421, PubMed:17988971). Up-regulated in macrophages and blood mononuclear cells treated with TNFSF11/RANKL.|||Recycling endosome membrane|||The subcellular localization of NHA2 remains controversial. Was initially thought to partially localize to mitochondria (PubMed:17988971). It was later established that its predominant localization is in endosomes and lysosomes (PubMed:20441802). In another recent study, endogenous SLC9B2 in the distal tubular cell line mpkDCT4 is detected in recycling endosomes but absent in plasma membrane (PubMed:32956652).|||Widely expressed (PubMed:18000046, PubMed:18508966, PubMed:17988971). However expression seems to be restricted to specific cell types within individual organs, e.g. osteoclasts in the bone, distal tubules of the kidney or beta-cells of Langerhans islets (PubMed:18508966, PubMed:17988971, PubMed:17698421, PubMed:23720317, PubMed:18269914, PubMed:32956652). In sperm specifically present in the principal piece of sperm tail (at protein level) (PubMed:27010853).|||flagellum membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Cfap43 ^@ http://purl.uniprot.org/uniprot/E9Q7R9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CFAP43 family.|||During embryonic development, detected in the left-right organizer at 8.25 dpc and in 17.5 dpc embryos, detected in epithelial cells lining the respiratory tract, brain ependymal cells and the choroid plexus.|||Expressed in testis (PubMed:28552195). Expressed in the lung, brain, oviduct and nasal cavity (PubMed:31884020).|||Flagellar protein involved in sperm flagellum axoneme organization and function (PubMed:28552195, PubMed:29449551, PubMed:31884020). Involved in the regulation of the beating frequency of motile cilia on the epithelial cells of the respiratory tract (PubMed:31884020).|||Mice are viable and show no malformations. However, homozygous males exhibit complete male sterility due to severe defects in sperm mobility. Sperm from mutant mice exhibits teratozoospermia characterized by short, thick, and coiled flagella and sperm axonemal defects. Females are fertile and give litters of normal size (PubMed:28552195, PubMed:29449551, PubMed:31884020). Mice display early onset hydrocephalus and severe mucus accumulation in the nasal cavity (PubMed:31884020).|||cilium axoneme|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:P2rx5 ^@ http://purl.uniprot.org/uniprot/B9EHM6|||http://purl.uniprot.org/uniprot/Q3UYI1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the P2X receptor family.|||Functional P2XRs are organized as homomeric and heteromeric trimers.|||Membrane|||Receptor for ATP that acts as a ligand-gated ion channel. http://togogenome.org/gene/10090:Gmppb ^@ http://purl.uniprot.org/uniprot/Q8BTZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with GMPPA.|||Belongs to the transferase hexapeptide repeat family.|||Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids.|||Cytoplasm http://togogenome.org/gene/10090:Aldh9a1 ^@ http://purl.uniprot.org/uniprot/Q3TMT4|||http://purl.uniprot.org/uniprot/Q3V1N7|||http://purl.uniprot.org/uniprot/Q9JLJ2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldehyde dehydrogenase family.|||Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine with high efficiency (in vitro). Can catalyze the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction, but with low efficiency.|||Homotetramer.|||Produced by alternative initiation. Contains a predicted signal peptide at positions 1-21.|||cytosol http://togogenome.org/gene/10090:Tacc2 ^@ http://purl.uniprot.org/uniprot/E9Q8T1|||http://purl.uniprot.org/uniprot/E9Q9Z4|||http://purl.uniprot.org/uniprot/E9QL08|||http://purl.uniprot.org/uniprot/Q3UL40|||http://purl.uniprot.org/uniprot/Q9JJG0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TACC family.|||Cytoplasm|||Expressed in brain, kidney, lung, thymus and ovary. Not detectable in normal tissues at protein level.|||Interacts with microtubules. Interacts with YEATS4, GCN5L2 and PCAF (By similarity). Interacts with CCDC100/CEP120.|||Mice develop normally, are fertile, and do not present elevated tumorization rates. Cells deficient in TACC2 divide normally and do not show any change in the frequency of apoptosis induction.|||Nucleus|||Phosphorylated; which is required for localization in centrosome.|||Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors. May play a role in organizing centrosomal microtubules (By similarity).|||centrosome http://togogenome.org/gene/10090:Clns1a ^@ http://purl.uniprot.org/uniprot/Q923F1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the pICln (TC 1.A.47) family.|||Nucleus http://togogenome.org/gene/10090:Nol4 ^@ http://purl.uniprot.org/uniprot/P60954 ^@ Subcellular Location Annotation ^@ nucleolus http://togogenome.org/gene/10090:Nfatc4 ^@ http://purl.uniprot.org/uniprot/Q8K120 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ca(2+)-regulated transcription factor that is involved in several processes, including the development and function of the immune, cardiovascular, musculoskeletal, and nervous systems. Involved in T-cell activation, stimulating the transcription of cytokine genes, including that of IL2 and IL4 (PubMed:17198697). Along with NFATC3, involved in embryonic heart development (PubMed:12750314, PubMed:17198697). Involved in mitochondrial energy metabolism required for cardiac morphogenesis and function (PubMed:12750314). Transactivates many genes involved in heart physiology. Along with GATA4, binds to and activates NPPB/BNP promoter (PubMed:9568714). Activates NPPA/ANP/ANF and MYH7/beta-MHC transcription (By similarity). Binds to and transactivates AGTR2 gene promoter (PubMed:17198697). Involved in the regulation of adult hippocampal neurogenesis. Involved in BDNF-driven pro-survival signaling in hippocampal adult-born neurons. Involved in the formation of long-term spatial memory and long-term potentiation (PubMed:22586092). In cochlear nucleus neurons, may play a role in deafferentation-induced apoptosis during a developmental critical period when auditory neurons depend on afferent input for survival (PubMed:18354019). Binds to and activates the BACE1/Beta-secretase 1 promoter, hence may regulate the proteolytic processing of the amyloid precursor protein (APP). Plays a role in adipocyte differentiation. May be involved in myoblast differentiation into myotubes (By similarity). Binds the consensus DNA sequence 5'-GGAAAAT-3' (Probable). In the presence of CREBBP, activates TNF transcription. Binds to PPARG gene promoter and regulates its activity (By similarity). Binds to PPARG and REG3G gene promoters (PubMed:17198697).|||Cytoplasm|||Expressed at high levels in the embryonic brain at 13.5 dpc (PubMed:18675896, PubMed:22586092). Expression decreases thereafter, reaching the lowest levels at postnatal day 14 and remaining unchanged in adulthood (PubMed:18675896). Expressed in the developing heart at 13.5 and 16.5 dpc, during the transition from spongy to compact myocardium (PubMed:17198697).|||Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other NFAT proteins, such as NFATC3, or members of the activating protein-1 (AP-1) family and MAF can also bind the complex. NFAT proteins can bind DNA as monomers or dimers (Probable). Interacts with CREBBP; this interaction potentiates transcription activation (By similarity). Interacts with MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts with GATA4 (via the second Zn finger) (PubMed:9568714). Interacts (via N-terminus) with IRAK1 (via C-terminus) (By similarity). Interacts with RPS6KA3 (By similarity). Interacts with HOMER1, HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC4 dephosphorylation and activation (By similarity). Interacts with ESR1 and ESR2; this interaction decreases NFATC4 transcriptional activity (By similarity). Interacts with MTOR and MAPK7/ERK5 (By similarity). Interacts with TRIM17; this interaction prevents NFATC3 nuclear localization (PubMed:25215946).|||No visible phenotype (PubMed:12370307). However, adult mutant animals show selective impairment in the formation of spatial long-term memory and long-term potentiation. They exhibit a reduced number of hippocampal adult-born neurons compared to wild-type littermates (PubMed:22586092). Simultaneous knockout of NFATC3 and NFATC4 results in embryonic death soon after 10.5 dpc. Embryos appear normal at 9.5 dpc. At 10.5 dpc, they exhibit defects in cardiac development, including dilated thin translucent hearts, pericardial effusion and anemia. Despite a mild generalized developmental delay, the heads, tails, and limb buds are well developed. By 11.5 dpc, mutant embryos are either necrotic or resorbed (PubMed:12750314).|||Nucleus|||Phosphorylated by NFATC-kinases; dephosphorylated by calcineurin/PPP3CA. Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8 and MAPK9, and on Ser-289 and Ser-344 by RPS6KA3 (PubMed:18691762). Phosphorylated by GSK3B (By similarity). Phosphorylation by GSK3B markedly increases NFATC4 ubiquitination (By similarity). Phosphorylation by MAPK8/JNK1, MAPK9/JNK2 and RPS6KA3 may stimulate NFATC4 transcriptional activity. Phosphorylation at Ser-168 and Ser-170 is stimulated by UV irradiation (By similarity).|||Rel similarity domain (RSD) or Rel homology domain (RHD) allows DNA-binding and cooperative interactions with AP-1 factors.|||Ubiquitinated, leading to degradation by the proteasome. Ubiquitination may be stimulated by GSK3B-dependent phosphorylation. Polyubiquitin linkage mainly occurs through 'Lys-48'.|||Up-regulated by BDNF.|||Widely expressed (PubMed:18675896). In the brain, expressed in neurons (PubMed:18675896, PubMed:25663301). Expressed in the hippocampus (at protein level) (PubMed:25663301). In the hippocampus, expressed in both the CA1-CA3 pyramidal cells and the dentate gyrus granular cells (PubMed:22586092). Expressed in a subset of hippocampal cells representing adult-born neurons (at protein level) (PubMed:22586092). Expressed in the submandibular gland (at protein level) (PubMed:21435446). In the olfactory system, expressed at low levels in the glomerular and granular layers and in the mitral cell layer (PubMed:18675896). In the cerebellum, expressed at moderate levels in granular neurons (PubMed:18675896). Expressed at moderate levels in the choroid plexus and ependymal cells (PubMed:18675896). Expressed in neurons of the cochlear nucleus (at protein level) (PubMed:18354019). Expressed at low levels in the heart (at protein level) (PubMed:12370307). http://togogenome.org/gene/10090:Phf11a ^@ http://purl.uniprot.org/uniprot/Q8BVM9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sh3yl1 ^@ http://purl.uniprot.org/uniprot/O08641 ^@ Developmental Stage|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the SH3YL1 family.|||Expressed in skin, kidney, stomach, small intestine and colon. Highly expressed in the anagen hair follicle. In hair, it is expressed predominantly in the hair bulb, the hair shaft, inner root sheath, and outer root sheath in the lower half of the follicle.|||In skin, expression follows hair-growth cycle, increasing significantly during mid and late anagen phases, and decreases during catagen, telogen and early anagen phases.|||Interacts with SH3D19. http://togogenome.org/gene/10090:Nr4a1 ^@ http://purl.uniprot.org/uniprot/P12813|||http://purl.uniprot.org/uniprot/Q545Q1 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by p300/CBP, acetylation increases stability. Deacetylated by HDAC1 (By similarity).|||Belongs to the nuclear hormone receptor family. NR4 subfamily.|||Binds 2 zinc ions.|||Binds the NGFI-B response element (NBRE) as a monomer (By similarity). Binds the Nur response element (NurRE), consisting of two inverse NBRE-related octanucleotide repeats separated by 6 base-pairs, as a dimer (By similarity). Interacts (via N-terminus) with NLRP3 (via LRR repeat domain); the interaction is direct, requires binding of NR4A1/Nur77 to NBRE-containing dsDNA and lipopolysaccharide, and leads to non-canonical NLRP3 inflammasome activation (PubMed:37001519). Interacts with GADD45GIP1. Interacts with STK11 (By similarity). Interacts with IFI27 (By similarity). Heterodimer (via DNA-binding domain) with RXRA (via C-terminus); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid (By similarity). Competes for the RXRA interaction with EP300 and thereby attenuates EP300 mediated acetylation of RXRA (By similarity). Interacts with NCOA1 (By similarity). Interacts with NCOA2 (By similarity). Interacts with NCOA3 (By similarity).|||By serum growth factors and during liver regeneration.|||Expressed in testis, thymus, brain, and heart, and at lower levels in ovaries and spleen.|||Highest levels are found in the adult with barely detectable levels in pre- and early postnatal tissue.|||Homozygous knockout mice display restenosis, the narrowing of blood vessels upon vascular injury (PubMed:22427340). Mutant mice do not robustly raise blood glucose levels or increase the expression of genes involved in gluconeogenesis in response to injection of cytosporone B (PubMed:18690216). They do not exhibit any increase in serum IL1B after administration of lipopolysaccharide (LPS) (PubMed:37001519). When challenged with LPS, mutant mice are partially resistant to endotoxic shock (PubMed:37001519).|||In the cytosol, upon its detection of both bacterial lipopolysaccharide (LPS) and NBRE-containing mitochondrial DNA released by GSDMD pores during pyroptosis, it promotes non-canonical NLRP3 inflammasome activation by stimulating association of NLRP3 and NEK7.|||Mitochondrion|||Nucleus|||Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5'-AAAGGTCA-3' (PubMed:37001519). Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain (By similarity). Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation (By similarity). Regulates the inflammatory response in macrophages by regulating metabolic adaptations during inflammation, including repressing the transcription of genes involved in the citric acid cycle (TCA) (PubMed:30134173). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter (PubMed:30134173). May act concomitantly with NR4A2 in regulating the expression of delayed-early genes during liver regeneration (By similarity). Plays a role in the vascular response to injury (PubMed:22427340).|||Phosphorylated at Ser-354 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.|||The NR LBD domain binds the lipid A moiety of lipopolysaccharide (LPS) in the cytosol.|||cytosol http://togogenome.org/gene/10090:Tex9 ^@ http://purl.uniprot.org/uniprot/Q9D845 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Testis-specific.|||centriolar satellite http://togogenome.org/gene/10090:Dph1 ^@ http://purl.uniprot.org/uniprot/Q5NCQ5 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DPH1/DPH2 family. DPH1 subfamily.|||Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:15485916, PubMed:24895408). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase (By similarity). Acts as a tumor suppressor (PubMed:14744934, PubMed:15661533, PubMed:24895408).|||Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase (By similarity). Interacts with DPH2 (PubMed:15485916, PubMed:21203470). Interacts with RBM8A (By similarity).|||Cytoplasm|||Expressed in heart, neural tube, forebrain, mandible, tongue and body walls at 10.5 to 14.5 dpc (at protein level) (PubMed:24895408). Expressed in lung, stomach, brain, heart, kidney and gonads at 14.5 dpc (PubMed:11527402).|||Global developmental delay (PubMed:14744934, PubMed:24895408). Abnormal palatogenesis; palatine bone absent, micrognathia, cleft palate and small skull (PubMed:14744934, PubMed:24895408). Results in death during gestation or soon after birth with a small body size (PubMed:14744934). May also result in preaxial polydactyly of the right hindlimb and abnormal hepatic development (PubMed:14744934). Knockout mice leads to an increased frequency of tumor formation (PubMed:14744934, PubMed:24895408).|||Nucleus|||Strongly expressed in kidney and liver. Moderately expressed in brain, skin and testis. Weakly expressed in heart, lung, small intestine, spleen, stomach and thymus. http://togogenome.org/gene/10090:B3gnt5 ^@ http://purl.uniprot.org/uniprot/Q8BGY6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylglucosaminyltransferase that plays a key role in the synthesis of lacto- or neolacto-series carbohydrate chains on glycolipids, notably by participating in biosynthesis of HNK-1 and Lewis X carbohydrate structures. Has strong activity toward lactosylceramide (LacCer) and neolactotetraosylceramide (nLc(4)Cer; paragloboside), resulting in the synthesis of Lc(3)Cer and neolactopentaosylceramide (nLc(5)Cer), respectively. Plays a central role in regulating neolacto-series glycolipid synthesis during embryonic development.|||Golgi apparatus membrane|||Highly expressed in adult spleen, placenta and cerebellar Purkinje cells where it colocalizes with HNK-1. Expressed at lower level in brain, lung, thymus and muscle.|||Mainly expressed during embryonic development. Expressed in most tissues at embryonic day 11 with elevated expression in the developing central nervous system. http://togogenome.org/gene/10090:Adam12 ^@ http://purl.uniprot.org/uniprot/Q61824 ^@ Cofactor|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At the onset of myoblast fusion.|||Binds 1 zinc ion per subunit.|||Expressed during early developing mesenchymal cells that give rise to skeletal muscle, bones and visceral organs. Not expressed in adult normal muscle but expressed in regenerating muscle.|||Interacts with alpha-actinin-2 and with syndecans. Interacts with SH3PXD2A. Interacts with FST3. Interacts with RACK1; the interaction is required for PKC-dependent translocation of ADAM12 to the cell membrane (By similarity).|||Involved in skeletal muscle regeneration, specifically at the onset of cell fusion. Also involved in macrophage-derived giant cells (MGC) and osteoclast formation from mononuclear precursors.|||Marker of skeletal muscle regeneration.|||Membrane|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The cysteine-rich domain supports cell adhesion through syndecans and triggers signaling events that lead to beta-1 integrin-dependent cell spreading. In carcinoma cells the binding of this domain to syndecans does not allow the integrin-mediated cell spreading (By similarity).|||The first 30 amino acids of the cytoplasmic domain contain a major binding site to alpha-actinin-2. This interaction is necessary to promote muscle cell fusion.|||The precursor is cleaved by a furin endopeptidase. http://togogenome.org/gene/10090:Lasp1 ^@ http://purl.uniprot.org/uniprot/Q543N3|||http://purl.uniprot.org/uniprot/Q61792 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with F-actin. Interacts with KBTBD10 (By similarity). Interacts with ANKRD54.|||Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types (By similarity).|||Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Pafah1b1 ^@ http://purl.uniprot.org/uniprot/P63005|||http://purl.uniprot.org/uniprot/Q5SW18 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat LIS1/nudF family.|||Can self-associate. Interacts with DCX, dynein, dynactin, IQGAP1, KATNB1, NDE1, NDEL1, NUDC and RSN. Interacts with DISC1, and this interaction is enhanced by NDEL1. Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling. Component of cytosolic PAF-AH IB, which is composed of PAFAH1B1 (alpha), PAFAH1B2 (beta) and PAFAH1B3 (gamma) subunits. Trimer formation is not essential for the catalytic activity of the enzyme which is contributed solely by the PAFAH1B2 (beta) and PAFAH1B3 (gamma) subunits.|||Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity. Interacts with the catalytic dimer of PAF-AH (I) heterotetrameric enzyme: interacts with PAFAH1B2 homodimer (alpha2/alpha2 homodimer), PAFAH1B3 homodimer (alpha1/alpha1 homodimer) and PAFAH1B2-PAFAH1B3 heterodimer (alpha2/alpha1 heterodimer) (PubMed:11344260, PubMed:12885786, PubMed:16481446). Can self-associate (PubMed:11163259, PubMed:11344260, PubMed:12885786, PubMed:15572112). Interacts with DCX, dynein, dynactin, IQGAP1, KATNB1, NDE1, NDEL1, NUDC, and RSN (PubMed:11001923, PubMed:11056530, PubMed:11163258, PubMed:11163259, PubMed:11163260, PubMed:11231056, PubMed:11940666, PubMed:12885786, PubMed:15173193, PubMed:15473966, PubMed:15473967, PubMed:15572112, PubMed:16203747, PubMed:16291865, PubMed:16481446, PubMed:16369480). Interacts with DAB1 when DAB1 is phosphorylated in response to RELN/reelin signaling (PubMed:14578885). Interacts with INTS13 (PubMed:23097494). Interacts with DCDC1 (By similarity). Interacts with DISC1, and this interaction is enhanced by NDEL1 (By similarity).|||Dimerization mediated by the LisH domain may be required to activate dynein.|||Double heterozygous PAFAH1B1 and homozygous VLDLR knockout mice present no obvious cortical layering defects (PubMed:17330141). Double heterozygous PAFAH1B1 and homozygous LRP8 knockout mice display a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization (PubMed:17330141).|||Embryonic expression begins prior to the blastocyst stage, when maternally expressed protein is depleted. By 10.5 dpc, expression is abundant in the developing central and peripheral nervous systems. Major sites of expression include the neuroepithelium of the fore-, mid-, and hindbrain, the spinal cord, the dorsal root and the cranial ganglia. By 13.5 dpc, highly expressed in neuroblasts as well as postmitotic neurons of the cortical plate. After completion of neuronal migration expression remains high in the cortex. Also expressed in the testis from P8.|||Highly expressed in brain, particularly the hippocampus and the olfactory bulb. Also highly expressed in testis, including all seminiferous tubule cell types, all types of spermatogenic and Sertoli cells, and meiotically dividing and elongating spermatids. Expressed at lower levels in heart, kidney, large intestine, liver, lung, ovary, small intestine and spleen.|||Nucleus membrane|||Originally the subunits of the type I platelet-activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1), beta (PAFAH1B2) and gamma (PAFAH1B3) (By similarity). Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2) and alpha1 (PAFAH1B3) respectively (By similarity).|||Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position.|||Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (By similarity). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (PubMed:17330141).|||centrosome|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Trdn ^@ http://purl.uniprot.org/uniprot/E9Q9K5 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contributes to the regulation of lumenal Ca2+ release via the sarcoplasmic reticulum calcium release channels RYR1 and RYR2, a key step in triggering skeletal and heart muscle contraction. Required for normal organization of the triad junction, where T-tubules and the sarcoplasmic reticulum terminal cisternae are in close contact. Required for normal skeletal muscle strength (PubMed:19843516). Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats.|||Detected in heart (at protein level). Detected in heart.|||Homooligomer of variable subunit number; disulfide-linked. Interacts with CASQ1 and RYR1 in skeletal muscle. Interacts with CASQ2.|||Mice appear normal; they are viable and fertile but have reduced muscular strength, due to defects in the structure of the triad junction, where T-tubules and the sarcoplasmic reticulum terminal cisternae are in close contact. In mutant mice, about 25% of the triads are in oblique or longitudinal orientation, instead of the normal transversal orientation (PubMed:19843516). Similar structural defects are seen in the heart, leading to impaired excitation-contraction coupling. Mutant mice are subject to stress-induced ventricular tachycardia (PubMed:19383796).|||N-glycosylated.|||Phosphorylated by CaMK2.|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Mfap1b ^@ http://purl.uniprot.org/uniprot/C0HKD8|||http://purl.uniprot.org/uniprot/C0HKD9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MFAP1 family.|||Component of the spliceosome B complex. Interacts with PRPF38A (via N-terminal interaction domain).|||Involved in pre-mRNA splicing as a component of the spliceosome.|||Nucleus http://togogenome.org/gene/10090:Dusp22 ^@ http://purl.uniprot.org/uniprot/Q99N11 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activates the Jnk signaling pathway.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Monomer.|||Myristoylation regulates subcellular location, and is necessary for activation of JNK.|||The publication has been retracted as they duplicated images. http://togogenome.org/gene/10090:Liph ^@ http://purl.uniprot.org/uniprot/Q8CIV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Cell membrane|||Expressed in placenta and colon. Weakly expressed in small intestine.|||Hydrolyzes specifically phosphatidic acid (PA) to produce 2-acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and fatty acid (By similarity). Does not hydrolyze other phospholipids, like phosphatidylserine (PS), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) or triacylglycerol (TG) (By similarity).|||Interacts with TTMP/C3orf52.|||Secreted http://togogenome.org/gene/10090:Gpr35 ^@ http://purl.uniprot.org/uniprot/Q3TBY9|||http://purl.uniprot.org/uniprot/Q3TU48|||http://purl.uniprot.org/uniprot/Q8BS98|||http://purl.uniprot.org/uniprot/Q8CB97|||http://purl.uniprot.org/uniprot/Q9ES90 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a receptor for kynurenic acid, an intermediate in the tryptophan metabolic pathway. The activity of this receptor is mediated by G-proteins that elicit calcium mobilization and inositol phosphate production through G(qi/o) proteins.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Predominantly expressed in immune and gastrointestinal tissues. http://togogenome.org/gene/10090:Cdkn2aip ^@ http://purl.uniprot.org/uniprot/Q8BI72 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CARF family.|||Interacts with CDKN2A/p14ARF, p53/TP53 and MDM2. Interacts with CHEK2 and MAPK3. Interacts with XRN2.|||May be ubiquitinated.|||Regulates DNA damage response and cell proliferation in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence.|||nucleoplasm http://togogenome.org/gene/10090:Heatr1 ^@ http://purl.uniprot.org/uniprot/G3X9B1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HEATR1/UTP10 family.|||Involved in nucleolar processing of pre-18S ribosomal RNA.|||nucleolus http://togogenome.org/gene/10090:Pld5 ^@ http://purl.uniprot.org/uniprot/D3YYN6|||http://purl.uniprot.org/uniprot/Q3UNN8 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the phospholipase D family.|||In contrast to other members of the family, it lacks the conserved active sites, suggesting that it has no phospholipase activity.|||Membrane http://togogenome.org/gene/10090:Sh3gl1 ^@ http://purl.uniprot.org/uniprot/Q3TRJ7|||http://purl.uniprot.org/uniprot/Q62419 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes.|||Belongs to the endophilin family.|||Cytoplasm|||Early endosome membrane|||Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity).|||Interacts with ARC, SYNJ1 and DNM1. Interacts with PDCD6IP. Interacts with BIN2 (By similarity).|||Membrane|||podosome http://togogenome.org/gene/10090:Slc36a1 ^@ http://purl.uniprot.org/uniprot/Q8K4D3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Electrogenic proton/amino acid symporter with selectivity for small apolar L-amino acids, their D-enantiomers and selected amino acid derivatives such as 4-aminobutanoate/GABA (PubMed:11959859). May be involved in the efflux from the lysosomal compartment of neutral amino acids resulting from proteolysis (By similarity). May play a role in specifying sites for exocytosis in neurons (By similarity).|||Highly expressed in small intestine, colon, kidney and brain.|||Lysosome membrane http://togogenome.org/gene/10090:Acbd3 ^@ http://purl.uniprot.org/uniprot/Q8BMP6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain (hippocampus, olfactory bulb, neuronal and glial cells of the cortex), eye, submaxillary gland, testis (interstitial and tubular compartments), ovary (granulosa cells, theca cells at late stages and primary follicles), adrenal gland (fasciculata and glomerulosa cells), heart, liver, and steroidogenic cell lines.|||Golgi apparatus membrane|||Homodimer (By similarity). Interacts with the C-terminal cytoplasmic domain of giantin/GOLGB1 (By similarity). Interacts with PBR and PKA regulatory subunit RI-alpha. Does not interact with PKA regulatory subunit RI-beta nor PKA regulatory subunit RII-alpha (PubMed:11731621). Interacts (via Q domain) with PI4KB (via N-terminus) (By similarity). Interacts (via Q domain) with TBC1D22A and TBC1D22B; interactions with PI4KB and with TBC1D22A and TBC1D22B are mutually exclusive (By similarity). Interacts with C10ORF76 and RAB11B (By similarity).|||Involved in the maintenance of Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and Golgi (By similarity). Involved in hormone-induced steroid biosynthesis in testicular Leydig cells (PubMed:12711385). Recruits PI4KB to the Golgi apparatus membrane; enhances the enzyme activity of PI4KB activity via its membrane recruitment thereby increasing the local concentration of the substrate in the vicinity of the kinase (By similarity).|||Mitochondrion|||Present in embryo. Decreases before birth.|||The central Gln-rich region (Q domain) is involved in binding to PI4KB, TBC1D22A and TBC1D22B (By similarity). The C-terminal GOLD domain is essential for giantin binding. The GOLD domain is also involved in homodimerization (By similarity). http://togogenome.org/gene/10090:Btbd35f23 ^@ http://purl.uniprot.org/uniprot/Q99N64 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CUL3.|||Nucleus matrix|||Possible function in spermatogenesis. Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. http://togogenome.org/gene/10090:Epo ^@ http://purl.uniprot.org/uniprot/B7ZMY9|||http://purl.uniprot.org/uniprot/P07321|||http://purl.uniprot.org/uniprot/Q0VED9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the EPO/TPO family.|||Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3.|||Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.|||Secreted http://togogenome.org/gene/10090:Nfix ^@ http://purl.uniprot.org/uniprot/E9PUH7|||http://purl.uniprot.org/uniprot/P70257|||http://purl.uniprot.org/uniprot/Q3TYK3|||http://purl.uniprot.org/uniprot/Q5CZY4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTF/NF-I family.|||Binds DNA as a homodimer.|||Nucleus|||Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.|||Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication. Isoform NFIX1 acts as a transcriptional activator while isoform NFIX3 acts as a repressor.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Prl3d2 ^@ http://purl.uniprot.org/uniprot/Q8CGZ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Sh2b3 ^@ http://purl.uniprot.org/uniprot/D3Z3Y5|||http://purl.uniprot.org/uniprot/O09039 ^@ Function|||PTM|||Similarity ^@ Belongs to the SH2B adapter family.|||Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.|||Tyrosine phosphorylated. http://togogenome.org/gene/10090:Mapk3 ^@ http://purl.uniprot.org/uniprot/Q63844 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14. Interacts with TPR. Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, NISCH, and SGK1 (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with PEA15 (PubMed:11702783). Interacts with isoform 1 of MKNK2 and this binding prevents from dephosphorylation and inactivation (PubMed:16162500). Interacts with CDKN2AIP. Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs upon heat shock. Interacts with CAVIN4 (By similarity). Interacts with GIT1; this interaction is necessary for MAPK3 localization to focal adhesions (PubMed:15923189). Interacts with ZNF263 (By similarity). Interacts with EBF4.|||Cytoplasm|||Dually phosphorylated on Thr-203 and Tyr-205, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-205 (By similarity). Autophosphorylated on threonine and tyrosine residues in vitro. Phosphorylated upon FLT3 and KIT signaling (By similarity).|||Nucleus|||Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-203 and Tyr-205 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.|||Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD.|||caveola|||focal adhesion http://togogenome.org/gene/10090:Vmn1r223 ^@ http://purl.uniprot.org/uniprot/Q5SSA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stra6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J115|||http://purl.uniprot.org/uniprot/O70491 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By retinoic acid. Synergistically up-regulated by Wnt1 and retinoids in mammary epithelial cells.|||Cell membrane|||Contrary to predictions, contains nine transmembrane helices, with an extracellular N-terminus and a cytoplasmic C-terminus (By similarity). Besides, contains one long helix that dips into the membrane and then runs more or less parallel to the membrane surface (By similarity).|||During embryogenesis, strongly expressed in the periocular mesenchyme, in the developing eyes, in respiratory mesenchymes, and in respiratory and bronchial epithelium, as well as in the developing central nervous system and in different embryonic gut derivatives (the epithelium of the pharyngeal pouches, mesenchyme of the esophagus, stomach, intestine, and rectum). In Sertoli cells expression depends on the stage of the spermatogenic cycle. During early placentation, is expressed in the yolk sac membrane and the chorionic plate. Expression was no longer detected in the yolk sac membrane during mid-late gestation, but was found in the labyrinthine zone of the chorioallantoic placenta. Expressed during early dorsoventral limb patterning and during endochondral ossification.|||Functions as retinol transporter (PubMed:23839944, PubMed:24852372). Accepts all-trans retinol from the extracellular retinol-binding protein RBP4, facilitates retinol transport across the cell membrane, and then transfers retinol to the cytoplasmic retinol-binding protein RBP1. Retinol uptake is enhanced by LRAT, an enzyme that converts retinol to all-trans retinyl esters, the storage forms of vitamin A (By similarity). Contributes to the activation of a signaling cascade that depends on retinol transport and LRAT-dependent generation of retinol metabolites that then trigger activation of JAK2 and its target STAT5, and ultimately increase the expression of SOCS3 and inhibit cellular responses to insulin (PubMed:21368206, PubMed:23839944). Important for the homeostasis of vitamin A and its derivatives, such as retinoic acid and 11-cis-retinal (PubMed:22467576, PubMed:24852372). STRA6-mediated transport is particularly important in the eye, and under conditions of dietary vitamin A deficiency (PubMed:22467576, PubMed:23839944, PubMed:24852372). Does not transport retinoic acid (By similarity).|||Homodimer (By similarity). Interacts with JAK2 and STAT5. Interacts (via extracellular domains) with RBP4. Interacts (via cytoplasmic domains) with RBP1 (By similarity).|||Membrane|||No visible phenotype at birth (PubMed:22467576, PubMed:23839944, PubMed:24852372). Measurement of the eye diameter indicates a tendency towards slightly smaller eye diameter 6 weeks after birth, and this difference persists in 5 and 10 month old animals (PubMed:22467576). The retina inner and outer segments are shorter in mutant mice (PubMed:22467576, PubMed:24852372). The number of cone cells in the retina is reduced, giving rise to a reduced cone response to light stimulation (PubMed:22467576). The retinal pigment epithelium displays discolored regions, where cells have large vacuoles and a reduced melanin content (PubMed:24852372). Retina and retinal pigment epithelium from dark-adapted mutant mice display strongly reduced levels of all-trans-retinol, all-trans-retinyl palmitate, 11-cis-retinal, 11-cis-retinyl palmitate and all-trans-retinal (PubMed:22467576, PubMed:24852372). Electroretinograms (ERG) of dark-adapted retinas from mutant mice display reduced a- and b-wave amplitude in response to light (PubMed:22467576). In another knockout model, the electroretinogram shows a complete lack of response to light (PubMed:24852372). Dietary vitamin A supplements can alleviate the ocular retinoid deficiency, and can prevent the altered retinal responses to light observed in mutant mice (PubMed:24852372). Other tissues and organs (brain, heart, kidney, liver, lungs, muscle, pancreas, spleen, testis and white adipose tissue) display grossly normal retinoid levels in 12 week old mice kept on normal chow (PubMed:23839944). Embryonic development appears grossly normal, also when females are fed a vitamin A-deficient diet (PubMed:23839944). Embryonic eye development is altered, leading to persistent hyperplastic primary vitreous that forms a conical mass of cells between the optic nerve exit point and the lens in the eyes of mutant mice (PubMed:22467576). In contrast, persistent hyperplastic primary vitreous was not observed in another knockout experiment (PubMed:24852372).|||Phosphorylated on tyrosine residues in response to RBP4 binding (PubMed:21368206). Phosphorylation requires the presence of LRAT, suggesting it may be triggered by the uptake of retinol that is then metabolized within the cell to retinoids that function as signaling molecules (By similarity).|||The retinoic acid-induced activation is impaired in retinoic acid receptor gamma-null F9 cells.|||Widely expressed in the embryo (PubMed:9203140, PubMed:23839944). Detected in adult in the retinal pigment epithelium in the eye (PubMed:9203140, PubMed:22467576, PubMed:23839944, PubMed:24852372). In the adult, is highly expressed in cells that compose blood-organ barriers in the brain (choroid plexus and the brain microvascular), in testis (the basal layer of the seminiferous epithelium), in the yolk sac, and in the chorioallantoic placenta (PubMed:9203140, PubMed:23839944). Detected in white adipose tissue and skeletal muscle, but not in liver (at protein level) (PubMed:21368206). Widely expressed in adult, with high expression levels in the eye (PubMed:24852372). Detected in brain, cerebellum, testis, pituitary, pancreas, kidney, spleen, and female genital tract; and at very low levels in heart and lung (PubMed:9203140, PubMed:24852372). Not detected in liver (PubMed:9203140). http://togogenome.org/gene/10090:Tafazzin ^@ http://purl.uniprot.org/uniprot/H3BK99|||http://purl.uniprot.org/uniprot/I7HJS2|||http://purl.uniprot.org/uniprot/Q91WF0 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1',3'-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary for adequate mitochondrial function (PubMed:19114128, PubMed:21091282, PubMed:21068380, PubMed:23130124, PubMed:26114544, PubMed:30055293, PubMed:30389594). Its role in cellular physiology is to improve mitochondrial performance (By similarity). CL is critical for the coassembly of lipids and proteins in mitochondrial membranes, for instance, remodeling of the acyl groups of CL in the mitochondrial inner membrane affects the assembly and stability of respiratory chain complex IV and its supercomplex forms (By similarity). Catalyzes the transacylation between phospholipids and lysophospholipids, with the highest rate being between phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) and CL. Catalyzes both 1-acyl-sn-glycero-3-phosphocholine (lysophosphatidylcholine or LPC) reacylation and PC-CL transacylation, that means, it exchanges acyl groups between CL and PC by a combination of forward and reverse transacylations. Also catalyzes transacylations between other phospholipids such as phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine or PE) and CL, between PC and PE, and between PC and phosphatidate (1,2-diacyl-sn-glycero-3-phosphate or PA), although at lower rate. Not regiospecific, it transfers acyl groups into any of the sn-1 and sn-2 positions of the monolysocardiolipin (MLCL), which is an important prerequisite for uniformity and symmetry in CL acyl distribution. Cannot transacylate dilysocardiolipin (DLCL), thus, the role of MLCL is limited to that of an acyl acceptor. CoA-independent, it can reshuffle molecular species within a single phospholipid class. Redistributes fatty acids between MLCL, CL, and other lipids, which prolongs the half-life of CL. Its action is completely reversible, which allows for cyclic changes, such as fission and fusion or bending and flattening of the membrane. Hence, by contributing to the flexibility of the lipid composition, it plays an important role in the dynamics of mitochondria membranes. Essential for the final stage of spermatogenesis, spermatid individualization (By similarity). Required for the initiation of mitophagy (PubMed:25919711). Required to ensure progression of spermatocytes through meiosis (PubMed:26114544).|||Acyltransferase which is required to remodel newly synthesized phospholipid cardiolipin, a key component of the mitochondrial inner membrane. Required for the initiation of mitophagy. Required to ensure progression of spermatocytes through meiosis.|||Associates with multiple protein complexes.|||Belongs to the taffazin family.|||Impaired cardiolipin (CL) metabolism with accumulation of monolysocardiolipin (MLCL) and reduction of mature CL in embryonic stem cells, male sterility, reduced testis size and disruption in progression of spermatocytes through meiosis (PubMed:26114544). Spermatocytes fail to progress past the pachytene stage of meiosis and have higher levels of DNA double strand damage and increased levels of endogenous retrotransposon activity (PubMed:26114544). RNAi-mediated knockdown results in prenatal and perinatal lethality, impaired CL metabolism resulting in absence of tetralineoyl-cardiolipin and accumulation of MLCL in cardiac and skeletal muscle, abnormal ultrastructure of mitochondria and mitochondrial-associated membranes, impaired skeletal muscle contractile properties, early diastolic dysfunction, and cardiac abnormalities such as myocardial thinning, hypertrabeculation, non-compaction, defective ventricular septation and left ventricular dilation (PubMed:21091282, PubMed:21068380, PubMed:23130124, PubMed:30389594). RNAi-mediated knockdown also results in impaired CL metabolism in the brain with reduced total CL levels and significantly increased MLCL levels, impaired brain mitochondrial respiration, elevated brain production of reactive oxygen species, significant memory deficiency, derangement of the hippocampal CA1 neuronal layer and elevated microglia activity (PubMed:30055293). Hepatic CL levels remain normal (PubMed:30055293). RNAi-mediated knockdown does not affect resting metabolic rate but markedly impairs oxygen consumption rates during exercise and diminishes mitochondrial complex III activity (PubMed:23616771).|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||The HXXXXD motif is essential for acyltransferase activity.|||The enzyme was named after a masochistic character Tafazzi, once popular on Italian television, apparently due to the difficulty encountered for its identification and characterization.|||Widely expressed with highest expression in skeletal muscle and kidney. http://togogenome.org/gene/10090:Dlat ^@ http://purl.uniprot.org/uniprot/Q8BMF4 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2-oxoacid dehydrogenase family.|||Binds 1 lipoyl cofactor covalently.|||Delipoylated at Lys-131 and Lys-258 by SIRT4, delipoylation decreases the PHD complex activity.|||Mitochondrion matrix|||Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules. Interacts with PDK2 and PDK3. Interacts with SIRT4. Interacts with PDHB.|||The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. http://togogenome.org/gene/10090:Fetub ^@ http://purl.uniprot.org/uniprot/Q9QXC1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fetuin family.|||Female infertility due to a block early in fertilization. Oocytes undergo premature zona pellucida hardening.|||Liver, lung and tongue.|||Protease inhibitor required for egg fertilization. Required to prevent premature zona pellucida hardening before fertilization, probably by inhibiting the protease activity of ASTL, a protease that mediates the cleavage of ZP2 and triggers zona pellucida hardening.|||Secreted http://togogenome.org/gene/10090:Samd4b ^@ http://purl.uniprot.org/uniprot/G5E8A7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMAUG family.|||Cytoplasm http://togogenome.org/gene/10090:Cemip2 ^@ http://purl.uniprot.org/uniprot/Q5FWI3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CEMIP family.|||Cell membrane|||Cell surface hyaluronidase that mediates the initial cleavage of extracellular high-molecular-weight hyaluronan into intermediate-size hyaluronan of approximately 5 kDa fragments (PubMed:28246172, PubMed:37196767). Is very specific to hyaluronan; not able to cleave chondroitin sulfate or dermatan sulfate (PubMed:28246172). Has an essential function in systemic hyaluronan catabolism and turnover and regulates cell adhesion and migration via hyaluronan degradation at focal adhesion sites (PubMed:34624311, PubMed:33647313). Acts as a regulator of angiogenesis and heart morphogenesis by mediating degradation of extracellular hyaluronan, thereby regulating VEGF signaling (By similarity).|||Expressed ubiquitously at early stages of development. Expressed in the endocardial cells lining the ventricles and atria at 9.5 dpc.|||Widely expressed (PubMed:10767548, PubMed:28246172). Strongly expressed in endothelial cells in the subcapsular sinus of lymph nodes and in the liver sinusoid, two primary sites implicated in systemic hyaluronan turnover (PubMed:34624311). http://togogenome.org/gene/10090:Pi15 ^@ http://purl.uniprot.org/uniprot/Q8BS03 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CRISP family.|||N-glycosylated.|||Secreted|||Serine protease inhibitor which displays weak inhibitory activity against trypsin (By similarity). May play a role in facial patterning during embryonic development (By similarity).|||Weakly expressed. Expressed at low level in prostate, mammary gland, salivary gland and thyroid gland. http://togogenome.org/gene/10090:Odf4 ^@ http://purl.uniprot.org/uniprot/Q8VI88 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Component of the outer dense fibers (ODF) of spermatozoa which could be involved in sperm tail structure, sperm movement and general organization of cellular cytoskeleton.|||Expressed from late pachytene stage and expression persists during embryonic development.|||Expressed in testis.|||Membrane http://togogenome.org/gene/10090:Slc51a ^@ http://purl.uniprot.org/uniprot/Q8R000 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OST-alpha family.|||Cell membrane|||Endoplasmic reticulum membrane|||Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood (PubMed:15563450, PubMed:16317684, PubMed:17650074, PubMed:18292224, PubMed:22535958). Efficiently transports the major species of bile acids (taurocholate) (PubMed:16317684, PubMed:17650074, PubMed:18292224, PubMed:22535958). Taurine conjugates are transported more efficiently across the basolateral membrane than glycine-conjugated bile acids (PubMed:16317684). Can also transport steroids such as estrone 3-sulfate and dehydroepiandrosterone 3-sulfate, therefore playing a role in the enterohepatic circulation of sterols (By similarity). Able to transport eicosanoids such as prostaglandin E2 (By similarity).|||Interacts with SLC51B. The Ost-alpha/Ost-beta complex is a heterodimer composed of alpha (SLC51A) and beta (SLC51B) subunit.|||Mice are physically indistinguishable from wild-type mice but display strongly reduced transileal transport of taurocholate. Moreover, the bile acid pool size is significantly reduced, but fecal bile acid excretion is not elevated.|||N-glycosylated.|||Positively regulated via the bile acid-activated nuclear receptor farnesoid X receptor (NR1H4/FXR). Up-regulated in mice lacking Mrp4, but it is unable to compensate for the absence of Mrp4.|||Present at high levels in ileum. In ileum, it is restricted to the apical domain on the mature villus enterocytes with little detectable expression in the goblet cells or crypt enterocytes (at protein level). Expressed in kidney but not in heart, brain, liver, spleen, embryo, lung, thymus, ovary nor testis. http://togogenome.org/gene/10090:Prkag2 ^@ http://purl.uniprot.org/uniprot/Q91WG5 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive (By similarity).|||AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity).|||Belongs to the 5'-AMP-activated protein kinase gamma subunit family.|||Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.|||The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.|||The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 (By similarity). http://togogenome.org/gene/10090:Map3k5 ^@ http://purl.uniprot.org/uniprot/O35099 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by various stressors, including oxidative stress, endoplasmic reticulum stress, and calcium overload, as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) and lipopolysaccharide (LPS). Homophilic association of MAP3K5/ASK1 through the C-terminal coiled-coil domains and the heteromeric complex formation of MAP3K5/ASK1 with the reduced form of thioredoxin (TXN), constitutes an inactive form of the kinase. Upon ROS-induced dissociation of TXN from MAP3K5/ASK1, TRAF2 and TRAF6 are reciprocally recruited to MAP3K5/ASK1 and form the active MAP3K5/ASK1 signalosome, in which TRAF2 and TRAF6 appear to facilitate the active configuration of MAP3K5/ASK1. MAP3K5/ASK1 activity is also regulated through several phosphorylation and dephosphorylation events. Thr-845 is an activating phosphorylation site that is autophosphorylated and phosphorylated by MAP3K6/ASK2 and dephosphorylated by PPP5C. Ser-90 and Ser-1040 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1. Phosphorylation of Ser-973 induces association of MAP3K5/ASK1 with the 14-3-3 family proteins, which suppresses MAP3K5/ASK1 activity. Calcium/calmodulin-activated protein phosphatase calcineurin (PPP3CA) has been shown to directly dephosphorylate this site. SOCS1 binds to ASK1 by recognizing phosphorylation of Tyr-725 and induces MAP3K5/ASK1 degradation in endothelial cells. Also dephosphorylated and activated by PGAM5. Contains an N-terminal autoinhibitory domain.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in various adult mouse tissues including heart, brain, lung, liver and kidney.|||Homodimer when inactive (By similarity). Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF (By similarity). This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis (By similarity). Interacts with SOCS1 which recognizes phosphorylation of Tyr-725 and induces MAP3K5/ASK1 degradation in endothelial cells (By similarity). Interacts with the 14-3-3 family proteins such as YWHAB, YWHAE, YWHAQ, YWHAH, YWHAZ and SFN (By similarity). Interacts with ARRB2, BIRC2, DAB2IP, IGF1R, MAP3K6/ASK2, PIM1, PGAM5, SOCS1, STUB1, TRAF2 and TXN (By similarity). Interacts with ERN1 in a TRAF2-dependent manner (By similarity). Interacts with calcineurin subunit PPP3R1, PPP5C, PPM1L and TRAF6 (PubMed:15864310, PubMed:16648474, PubMed:17456047, PubMed:22399290). Interacts (via N-terminus) with RAF1 and this interaction inhibits the proapoptotic function of MAP3K5. Interacts with DAB2IP (via N-terminus C2 domain); the interaction occurs in a TNF-alpha-dependent manner (By similarity).Interacts with DUSP13A; may positively regulate apoptosis (By similarity). Interacts with PPIA/CYPA (By similarity). Interacts with PRMT1; the interaction results in MAP3K5 methylation by PRMT1 which inhibits MAP3K5 activation (By similarity). Interacts with TRAF2; the interaction is inhibited by PRMT1 (By similarity). Interacts with TRIM48 (By similarity).|||Methylation at Arg-85 and Arg-87 by PRMT1 promotes association of MAP3K5 with thioredoxin and negatively regulates MAP3K5 association with TRAF2, inhibiting MAP3K5 activation. Methylation is blocked by ubiquitination of PRMT1 by TRIM48.|||Ser-90 and Ser-1040 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 (By similarity). Phosphorylated at Ser-973 which induces association of MAP3K5/ASK1 with the 14-3-3 family proteins and suppresses MAP3K5/ASK1 activity (PubMed:16648474). Calcineurin (CN) dephosphorylates this site. Also dephosphorylated and activated by PGAM5 (By similarity). Phosphorylated at Thr-845 through autophosphorylation and by MAP3K6/ASK2 which leads to activation (PubMed:11920685, PubMed:18948261, PubMed:22399290). Thr-845 is dephosphorylated by PPP5C (PubMed:22399290). Phosphorylation at Ser-973 in response to oxidative stress is negatively regulated by PPIA/CYPA (By similarity).|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).|||Ubiquitinated. Tumor necrosis factor (TNF) induces TNFR2-dependent ubiquitination, leading to proteasomal degradation. Ubiquitinated by RC3H2 in a TRIM48-dependent manner. http://togogenome.org/gene/10090:Rb1 ^@ http://purl.uniprot.org/uniprot/P13405 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with SV40 large T antigen.|||(Microbial infection) Interacts with adenovirus E1a protein.|||Acetylated in the skin (PubMed:20940255). Acetylation at Lys-866 and Lys-867 regulates subcellular localization during keratinocytes differentiation (By similarity).|||Belongs to the retinoblastoma protein (RB) family.|||Expressed in the cell nuclei of renal tubules, hepatocytes and skeletal muscles. Expressed in skin (at protein level) (PubMed:20940255).|||Monomethylation at Lys-803 by SMYD2 enhances phosphorylation at Ser-800 and Ser-804, and promotes cell cycle progression. Monomethylation at Lys-853 by SMYD2 promotes interaction with L3MBTL1 (By similarity). N-terminus is methylated by METTL11A/NTM1.|||Nucleus|||Phosphorylated (PubMed:8336704). Phosphorylated by CDK6 and CDK4, and subsequently by CDK2 at Ser-561 in G1, thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. Phosphorylation of threonine residues in domain C promotes interaction between the C-terminal domain C and the Pocket domain, and thereby inhibits interactions with heterodimeric E2F/DP transcription factor complexes. Dephosphorylated at Ser-788 by calcineruin upon calcium stimulation. CDK3/cyclin-C-mediated phosphorylation at Ser-800 and Ser-804 is required for G0-G1 transition (By similarity). Phosphorylated by CDK1 and CDK2 upon TGFB1-mediated apoptosis (By similarity).|||The hypophosphorylated form interacts with and sequesters the E2F1 transcription factor. Interacts with heterodimeric E2F/DP transcription factor complexes containing TFDP1 and either E2F1/E2F, E2F3, E2F4 or E2F5, or TFDP2 and E2F4 (PubMed:8336704, PubMed:20940255). The unphosphorylated form interacts with EID1, ARID3B, KDM5A, SUV39H1, MJD2A/JHDM3A and THOC1. Interacts with the N-terminal domain of TAF1. Interacts with SNW1, ATAD5, AATF, DNMT1, LIN9, LMNA, KMT5B, KMT5C, PELP1, UHRF2, TMPO-alpha and USP4. May interact with NDC80. Interacts with GRIP1 and UBR4. Interacts with ARID4A and KDM5B. Interacts with E4F1 and LIMD1. Interacts with SMARCA4/BRG1 and HDAC1. Interacts with USP4. Interacts (when methylated at Lys-853) with L3MBTL1. Binds to CDK1 and CDK2. Interacts with CHEK2; phosphorylates RB1 (By similarity). Interacts with PRMT2. Interacts with CEBPA. P-TEFB complex interacts with RB1; promotes phosphorylation of RB1 (By similarity). Interacts with RBBP9; the interaction disrupts RB1 binding to E2F1 (By similarity). Interacts with KAT2B/PCAF and EP300/P300 (PubMed:20940255). Interacts with PAX5 (By similarity).|||Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:8336704). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes. Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription. Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase. RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (PubMed:15750587). Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation (PubMed:16612004). Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity) (PubMed:15750587, PubMed:16612004, PubMed:8336704). http://togogenome.org/gene/10090:Fmc1 ^@ http://purl.uniprot.org/uniprot/Q9CR13 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FMC1 family.|||Interacts with ATPAF2.|||Mitochondrion|||Plays a role in the assembly/stability of the mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V). http://togogenome.org/gene/10090:Btnl2 ^@ http://purl.uniprot.org/uniprot/O70355 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Highly expressed in intestine and at reduced levels in lung and stomach. Also expressed in thymus, spleen, lymph nodes, T-cells, B-cells, and macrophages.|||Membrane|||Negative regulator of T-cell proliferation. http://togogenome.org/gene/10090:H2ac15 ^@ http://purl.uniprot.org/uniprot/Q8CGP7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Gabpb1 ^@ http://purl.uniprot.org/uniprot/Q00420 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylated by EP300/p300 (PubMed:25200183). Deacetylated by SIRT7, promoting heterotetramerization and activity (PubMed:25200183).|||Heterotetramer of two alpha and two beta subunits (PubMed:25200183). Interacts with HCFC1, causing repression of transcriptional activity (By similarity).|||May be due to an intron retention.|||May be due to competing acceptor splice sites.|||Nucleus|||Transcription factor capable of interacting with purine rich repeats (GA repeats) (PubMed:25200183). Acts as a a master regulator of nuclear-encoded mitochondrial genes (PubMed:25200183). http://togogenome.org/gene/10090:Alcam ^@ http://purl.uniprot.org/uniprot/Q61490 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts. Promotes T-cell activation and proliferation via its interactions with CD6 (By similarity). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (By similarity). Mediates homotypic interactions with cells that express ALCAM (PubMed:24740813). Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction. Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions (PubMed:23169771). Required for normal organization of the lymph vessel network (PubMed:23169771). Required for normal hematopoietic stem cell engraftment in the bone marrow (PubMed:24740813). Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow (PubMed:25730656). Promotes in vitro osteoblast proliferation and differentiation (PubMed:25730656). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM (By similarity). Mediates outgrowth and pathfinding for retinal ganglion cell axons (PubMed:15345243).|||Cell membrane|||Detected on brain motor neurons, in differentiating retinal ganglion cells and in adult retina (PubMed:15345243). Detected on leukocytes and on lymphatic endothelial cells (PubMed:23169771). Detected in spleen B cells and T-cells (at protein level) (PubMed:9209500). Detected in adult brain and embryonic spinal cord (PubMed:15345243). Expressed at high levels in the brain, and lung, and at lower levels in the liver, and the kidney, as well as by activated leukocytes (PubMed:9209500).|||Glycosylated.|||Homodimer (By similarity). Interacts (via extracellular domain) with CD6 (via extracellular domain) (PubMed:9209500, PubMed:16914752). Homodimerization and interaction with CD6 involve the same region and cannot occur simultaneously. The affinity for CD6 is much higher than the affinity for self-association. Interacts (via glycosylated extracellular domain) with LGALS1 and LGALS3. Interaction with LGALS1 or LGALS3 inhibits interaction with CD6.|||Mice are born at the expected Mendelian rate, are viable and fertile and display no obvious external phenotype. Unlike wild-type mice, that have tightly fasciculated and smooth nerve bundles, mutant mice have more loosely bundled nerves with many single axons extending out of the main nerve. Eyes from mutant mice display a variable degree of retinal displasia (PubMed:15345243). Besides, lymph nodes from mutant mice display reduced weight and cellularity, but appear otherwise normal (PubMed:23169771). Mutant mice have only half of the normal number of hematopoietic stem cells in their bone marrow (PubMed:24740813, PubMed:25730656). Survival of lethally irradiated mice that receive bone marrow from mutant mice is impaired, due to impaired homotypic cell-cell attachment, impaired engraftment and proliferation of mutant hematopoietic stem cells (PubMed:24740813). Mutant mice are larger and heavier than wild-type and have increased bone mineral density (PubMed:25730656). Mutant spleen has an altered leukocyte composition, with reduced numbers of CD4(+) and CD8(+) T-cells, B-cells, dendritic cells, neutrophils and macrophages, but no change in the total leukocyte number. Their lungs display reduced numbers of lymph vessel and blood vessel endothelial cells, but no difference in lung weight. Lymph vessels in mesentery and diaphragm are more densely interconnected and show a decreased level of hierarchical vascular organization in mutant mice (PubMed:23169771).|||The CD6 binding site is located in the N-terminal Ig-like domain.|||axon|||dendrite http://togogenome.org/gene/10090:Rps12 ^@ http://purl.uniprot.org/uniprot/P63323 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS12 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity). Subunit of the 40S ribosomal complex (By similarity).|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity). Subunit of the 40S ribosomal complex (By similarity).|||nucleolus http://togogenome.org/gene/10090:Rpf1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFR7|||http://purl.uniprot.org/uniprot/Q7TND5 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Intron retention.|||May be required for ribosome biogenesis.|||nucleolus http://togogenome.org/gene/10090:Mdga2 ^@ http://purl.uniprot.org/uniprot/B2RQF5|||http://purl.uniprot.org/uniprot/P60755|||http://purl.uniprot.org/uniprot/Q3UV20 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts (through the Ig-like domains) with NLGN2.|||May be involved in cell-cell interactions.|||Membrane http://togogenome.org/gene/10090:Cdh3 ^@ http://purl.uniprot.org/uniprot/P10287|||http://purl.uniprot.org/uniprot/Q8BRE1 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cadherins are calcium-dependent cell adhesion proteins.|||Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.|||Cell membrane|||Expression is high in both fetal and newborn testis but minimal in testis of 7-day-old animals. Not detected in testis of 21-day-old or adult.|||Interacts with CDCP1 and CTNNB1.|||Membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Ank ^@ http://purl.uniprot.org/uniprot/Q3UG85|||http://purl.uniprot.org/uniprot/Q8C438|||http://purl.uniprot.org/uniprot/Q9JHZ2 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ANKH family.|||Cell membrane|||Defects in Ankh are the cause of a generalized, progressive form of arthritis. In ank mice hydroxyapatite crystals develop in articular surfaces and synovial fluid leading to joint space narrowing, cartilage erosion, and formation of bony outgrowths or osteophytes that cause fusion and joint immobility and destruction.|||Expressed in heart, brain, liver, spleen, lung, muscle, and kidney of adult animals. Strongly expressed in the developing articular cartilage of joints in the shoulder, elbow, wrist, and digits of the embryo.|||Membrane|||Mutant mice develop early-onset osteopenia in long bones associated with diminished bone strength. They show widespread calcification of soft connective tissues due to almost absence of PPi in plasma.|||Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.|||Transports adenosine triphosphate (ATP) and possibly other nucleoside triphosphates (NTPs) from cytosol to the extracellular space. Mainly regulates their levels locally in peripheral tissues while playing a minor systemic role. Prevents abnormal ectopic mineralization of the joints by regulating the extracellular levels of the calcification inhibitor inorganic pyrophosphate (PPi), which originates from the conversion of extracellular NTPs to NMPs and PPis by ENPP1. Regulates the release of the TCA cycle intermediates to the extracellular space, in particular citrate, succinate and malate. Extracellular citrate mostly present in bone tissue is required for osteogenic differentiation of mesenchymal stem cells, stabilization of hydroxyapatite structure and overall bone strength. The transport mechanism remains to be elucidated. http://togogenome.org/gene/10090:Snap23 ^@ http://purl.uniprot.org/uniprot/A2AKH4|||http://purl.uniprot.org/uniprot/O09044|||http://purl.uniprot.org/uniprot/Q9D3L3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type A (BoNT/A, botA) which hydrolyzes the 202-Thr-|-Arg-203 bond; the in vitro reaction is not highly efficient (PubMed:9886085).|||(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type E (BoNT/E) which hydrolyzes the 185-Arg-|-Ile-186 bond; the in vitro reaction is more efficient than that of BoNT/A (PubMed:9886085).|||Belongs to the SNAP-25 family.|||Cell membrane|||Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion.|||Expressed in non-neuronal tissues.|||Homotetramer (via coiled-coil domain), also forms heterotetramers with STX4 and VAMP3 (By similarity). Found in a complex with VAMP8 and STX1A (By similarity). Found in a complex with VAMP8 and STX4 in pancreas (PubMed:15363411). Interacts simultaneously with SNAPIN and SYN4 (By similarity). Interacts with STX1A (PubMed:9507000). Interacts with STX12 (PubMed:9507000). Interacts tightly to multiple syntaxins and synaptobrevins/VAMPs (By similarity). Interacts with ZDHHC13 (via ANK repeats) (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:26198635).|||Membrane|||synaptosome http://togogenome.org/gene/10090:Mrpl23 ^@ http://purl.uniprot.org/uniprot/O35972 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL23 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Chsy3 ^@ http://purl.uniprot.org/uniprot/Q5DTK1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Divalent metal cations. Highest activities are measured with Co(2+), Mn(2+) and Cd(2+).|||Golgi stack membrane|||Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Specific activity is much reduced compared to CHSY1. http://togogenome.org/gene/10090:Nrg4 ^@ http://purl.uniprot.org/uniprot/Q9WTX4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neuregulin family.|||Cell membrane|||ERBB receptor binding is elicited entirely by the EGF-like domain.|||Extensive glycosylation precedes the proteolytic cleavage.|||Highly expressed in pancreas; weakly expressed in muscle.|||Interacts with ERBB4.|||Low affinity ligand for the ERBB4 tyrosine kinase receptor. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. Does not bind to the ERBB1, ERBB2 and ERBB3 receptors.|||Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.|||Secreted|||The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity). http://togogenome.org/gene/10090:Rab2b ^@ http://purl.uniprot.org/uniprot/P59279 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts (in GTP-bound form) with GARIN4 (via N-terminus) (By similarity). Interacts (in GTP-bound form) with GARIN5A (PubMed:28930687). Interacts (in GTP-bound form) with GARIN1B (PubMed:34714330).|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states (PubMed:28930687). In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology (PubMed:28930687). Regulates the compacted morphology of the Golgi (By similarity). Promotes cytosolic DNA-induced innate immune responses. Regulates IFN responses against DNA viruses by regulating the CGAS-STING signaling axis (PubMed:28930687).|||acrosome http://togogenome.org/gene/10090:Zfp296 ^@ http://purl.uniprot.org/uniprot/E9Q6W4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||In testis, detected in condensing spermatids but not at earlier stages of spermatogenesis (PubMed:11063263). In embryonic stem cells, expressed in undifferentiated cells and down-regulated upon differentiation (PubMed:24161396).|||Interacts with KLF4.|||May be a transcriptional corepressor with KLF4.|||Nucleus|||Strongly expressed in testis and embryonic stem cells. http://togogenome.org/gene/10090:Kdm5b ^@ http://purl.uniprot.org/uniprot/Q80Y84 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JARID1 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Both the JmjC domain and the JmjN domain are required for enzymatic activity. However ARID and PHD-type 1 domain are not required for activity per se but contributed to recognition of the H3(1-21)K4me2 substrate peptide.|||Expressed in developing brain, mammary bud, thymus, teeth, whisker follicle, intervertebral disks, olfactory epithelium, eye, stomach and limbs.|||Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2.|||Homozygous KDM5B-null mice are subviable, exhibit vertebral patterning defects, and manifest numerous behavioral abnormalities including increased anxiety, less sociability, and reduced long-term memory compared with that of wild-types. Heterozygous mice appear normal.|||Interacts with FOXG1B, PAX9, MYC, MYCN and RB1. Interacts with HDAC1, HDAC4, HDAC5 and HDAC7. Interacts (via PHD-type 1 zinc finger) with histone H3 unmodified at 'Lys-4'; the interaction is inhibited when histone H3 is methylated at 'Arg-2' or 'Lys-4' (By similarity).|||Nucleus|||Present at highest levels in testis, where it is enriched in spermatogonia and pachytene cells (at protein level).|||The 2 first PHD-type zinc finger domains are required for transcription repression activity. http://togogenome.org/gene/10090:Pla2g15 ^@ http://purl.uniprot.org/uniprot/Q8VEB4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Detected in blood plasma (PubMed:20410020). Detected in alveolar macrophages (at protein level) (PubMed:16106046, PubMed:16880524, PubMed:19017977). Detected in heart, liver, spleen, kidney, thymus, brain and lung (PubMed:16880524).|||Has dual calcium-independent phospholipase and O-acyltransferase activities with a potential role in glycerophospholipid homeostasis and remodeling of acyl groups of lipophilic alcohols present in acidic cellular compartments (PubMed:16837646, PubMed:17626977, PubMed:11790796, PubMed:16106046, PubMed:16880524, PubMed:19017977, PubMed:20410020). Catalyzes hydrolysis of the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 or A2 activity) and transfer it to the hydroxyl group at the first carbon of lipophilic alcohols (O-acyltransferase activity). Among preferred fatty acyl donors are phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols and phosphatidylserines (PubMed:20410020). Favors sn-2 over sn-1 deacylation of unsaturated fatty acyl groups of phosphatidylcholines and phosphatidylethanolamines (PubMed:16837646, PubMed:17626977). Among preferred fatty acyl acceptors are natural lipophilic alcohols including short-chain ceramide N-acetyl-sphingosine (C2 ceramide), alkylacylglycerols, monoacylglycerols, and acylethanolamides such as anandamide and oleoylethanolamide (PubMed:16837646, PubMed:17626977). Selectively hydrolyzes the sn-1 fatty acyl group of truncated oxidized phospholipids and may play a role in detoxification of reactive oxidized phospholipids during oxidative stress (PubMed:27993948). Required for normal phospholipid degradation in alveolar macrophages with potential implications in pulmonary surfactant clearance (PubMed:16880524, PubMed:19017977). At neutral pH, hydrolyzes the sn-1 fatty acyl group of the lysophosphatidylcholines (By similarity).|||Lysosome|||Membrane|||Mice are born at the expected Mendelian rate, are viable and fertile. They display strongly reduced transacylase activity in lung alveolar macrophages and in peritoneal macrophages, leading to the accumulation of pulmonary surfactant phospholipids with phosphatidylethanolamine and phosphatidylcholine headgroups. Mice display higher numers of alveolar macrophages in the lung, together with a mononuclear cell infiltrate in airways and blood vessels. Alveolar nmacrophages are larger than normal and present lamellar inclusion bodies, indicative of cellular phospholipidosis. Besides, mutant mice display splenomegaly.|||N-glycosylated (PubMed:11790796). N-glycosylation is important for maturation of the enzyme and normal subcellular location (By similarity).|||Phospholipase sn-2 versus sn-1 positional specificity is affected by the phospholipid composition of membranes. Phospholipase A2 activity toward 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine (PAPE) is enhanced in the presence of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), which promotes lipid bilayer formation (PubMed:16837646). O-acyltransferase activity is inhibited by antiarrhythmic drug amiodarone (PubMed:27993948).|||Secreted http://togogenome.org/gene/10090:Slc5a6 ^@ http://purl.uniprot.org/uniprot/Q3TY45|||http://purl.uniprot.org/uniprot/Q5U4D8 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Expressed in the intestinal mucosa, liver and kidney (at protein level) (PubMed:23104561). Expressed in the colon (PubMed:28052864).|||Interacts with PDZD11.|||Intestine-specific knockout leads to premature lethality between the age of 6 and 10 weeks in around two-thirds of mice due to acute peritonitis (PubMed:23104561). Growth retardation, decreased bone density of the femoral and humoral head, decreased bone length of the pelvic, tibial, and femoral bones, lethargic behavior, hunched back posture, and decreased biotin status are observed (PubMed:23104561). Abnormalities in the small bowel with shortened villi and dysplasia, chronic active inflammation with focal cryptitis/crypt abscesses in the cecum, an increase in the number of neutrophils in the mucosa and low-grade adenomatous changes and extensive submucosal edema (PubMed:23104561). Impaired carrier-mediated biotin and pantothenate uptake in the jejunum (PubMed:23104561). Reduced biotin levels in the liver (PubMed:23104561). Increase in gut permeability and changes in the level of expression of tight junction proteins in the cecum and colon (PubMed:27492331).|||Membrane|||Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide (PubMed:23104561). Functions as a Na(+)-coupled substrate symporter where the stoichiometry of Na(+):substrate is 2:1, creating an electrochemical Na(+) gradient used as driving force for substrate uptake (By similarity). Required for biotin and pantothenate uptake in the intestine across the brush border membrane (PubMed:23104561). Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (PubMed:27492331). Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (By similarity).|||The C-terminal tail is important for biotin uptake as well as apical localization in polarized cells. http://togogenome.org/gene/10090:Or11h4b ^@ http://purl.uniprot.org/uniprot/E9PXH6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhox12 ^@ http://purl.uniprot.org/uniprot/Q4TU81 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Kmt2c ^@ http://purl.uniprot.org/uniprot/F8WI37 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Gm2a ^@ http://purl.uniprot.org/uniprot/Q60648 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3. The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity. Has cholesterol transfer activity (By similarity).|||Lysosome|||Widely expressed. Most abundant in kidney and testis. http://togogenome.org/gene/10090:Gna13 ^@ http://purl.uniprot.org/uniprot/P27601|||http://purl.uniprot.org/uniprot/Q3UE40|||http://purl.uniprot.org/uniprot/Q9D034 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-alpha family. G(12) subfamily.|||Cytoplasm|||Expressed in brain and testis, as well as in kidney and sperm (at protein level).|||G proteins are composed of 3 units; alpha, beta and gamma (PubMed:16388592). The alpha chain contains the guanine nucleotide binding site (PubMed:16388592). Interacts with UBXD5 (By similarity). Interacts with HAX1 (By similarity). Interacts (in GTP-bound form) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane (By similarity). Interacts with RGS22 (By similarity). Interacts (in GTP-bound form) with ARHGEF1 (PubMed:16388592). Interacts (in GTP-bound form) with ARHGEF11 (via RGS domain) (PubMed:18940608). Interacts (in GTP-bound form) with ARHGEF12 (via RGS domain) (PubMed:16388592). Interacts with CTNND1 (PubMed:15240885). Interacts with GAS2L2 (PubMed:23994616).|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:21212405, PubMed:19151758, PubMed:16388592). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF1/p115RhoGEF, ARHGEF11/PDZ-RhoGEF and ARHGEF12/LARG) (PubMed:16388592). GNA13-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (PubMed:19151758, PubMed:21212405). Promotes tumor cell invasion and metastasis by activating Rho/ROCK signaling pathway (By similarity). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (By similarity).|||Melanosome|||Membrane|||Nucleus|||Phosphorylation on Thr-203 destabilizes the heterotrimer of alpha, beta and gamma, and inhibits Rho activation. http://togogenome.org/gene/10090:Cc2d1b ^@ http://purl.uniprot.org/uniprot/Q8BRN9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CC2D1 family.|||Nucleus|||Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. http://togogenome.org/gene/10090:Dlg2 ^@ http://purl.uniprot.org/uniprot/Q91XM9 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain. Highest levels of isoform 1 in cortex, olfactory bulb, thalamus, hypothalamus, striatum and hippocampus. Highest level of isoform 2 in olfactory bulb. Reduced levels in cortex and hippocampus. Highest level of isoform 4 in spinal cord. Low levels of isoform 4, isoform 6, and isoform 7 in superior cervical ganglion.|||Cell membrane|||Incomplete sequence.|||Interacts with NOS1/nNOS through second PDZ domain. Interacts with KCNJ2/Kir2.1 (via C-terminus) through one of its PDZ domains (By similarity). Interacts with KCNJ4 (PubMed:11997254). Interacts with FRMPD4 (via C-terminus) (By similarity). Interacts through its PDZ domains with NETO1 (PubMed:19243221). Interacts with LRFN1, LRFN2 and LRFN4. Interacts with FASLG (By similarity). Interacts with KCNJ4 (By similarity). Interacts with ADAM22 (PubMed:20089912). Interacts with DGKI (via PDZ-binding motif) (By similarity).|||Isoform 7 has an L27 domain close to N-terminus.|||Membrane|||Mice do not respond to persistent pain. Postsynaptic surface expression of NMDA receptors and NMDA receptor-mediated synaptic function are reduced in dorsal horn neurons of the spinal chord.|||Palmitoylation of isoform 1 and isoform 2 is not required for targeting to postsynaptic density.|||Perikaryon|||Postsynaptic density|||Required for perception of chronic pain through NMDA receptor signaling. Regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord. Interacts with the cytoplasmic tail of NMDA receptor subunits as well as inward rectifying potassium channels. Involved in regulation of synaptic stability at cholinergic synapses. Part of the postsynaptic protein scaffold of excitatory synapses.|||Synapse|||axon http://togogenome.org/gene/10090:Bax ^@ http://purl.uniprot.org/uniprot/Q07813|||http://purl.uniprot.org/uniprot/Q544Z6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with gamma-herpesvirus 68 protein vBCL2.|||Accelerates programmed cell death by binding to, and antagonizing the apoptosis repressor BCL2 or its adenovirus homolog E1B 19k protein. Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis. BAX deficiency leads to lymphoid hyperplasia and male sterility, because of the cessation of sperm production.|||Belongs to the Bcl-2 family.|||Cytoplasm|||Expressed in a wide variety of tissues.|||Homodimer. Forms higher oligomers under stress conditions. Forms heterooligomers with BAK (By similarity). Interacts with BCL2L11. Interaction with BCL2L11 promotes BAX oligomerization and association with mitochondrial membranes, with subsequent release of cytochrome c (PubMed:21060336). Forms heterodimers with BCL2 (PubMed:8358790, PubMed:21060336). Forms heterodimers with BCL2L1 isoform Bcl-X(L), BCL2L2, MCL1 and A1. Interacts with SH3GLB1. Interacts with SFN and YWHAZ; the interaction occurs in the cytoplasm. Under stress conditions, JNK-mediated phosphorylation of SFN and YWHAZ, releases BAX to mitochondria. Interacts with RNF144B, which regulates the ubiquitin-dependent stability of BAX. Interacts with CLU under stress conditions that cause a conformation change leading to BAX oligomerization and association with mitochondria. Does not interact with CLU in unstressed cells (By similarity). Interacts with FAIM2/LFG2 (By similarity). Interacts with BOP (By similarity). Interacts (via a C-terminal 33 residues) with NOL3 (via CARD domain); inhibits BAX activation and translocationand consequently cytochrome c release from mitochondria (PubMed:15383280). Interacts with GIMAP3/IAN4 and GIMAP5/IAN5; this interaction is increased, when cells initiate apoptosis upon IL2 withdrawal (PubMed:16509771). Interacts with IRF3; the interaction is direct and, upon virus infection, mediates the formation of the apoptosis complex TOMM70:HSP90AA1:IRF3:BAX (By similarity). Interacts with MOAP1, facilitating BAX-dependent mitochondrial outer membrane permeabilization and apoptosis (By similarity). Interacts with BCL2L10/BCL-B (By similarity).|||Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.|||Mitochondrion outer membrane|||Nucleus|||Ubiquitinated on Lys-128 and Lys-190. 'Lys-63'-linked polyubiquitin chains on Lys-128 are removed by USP12. http://togogenome.org/gene/10090:Tspan4 ^@ http://purl.uniprot.org/uniprot/Q4FJW7|||http://purl.uniprot.org/uniprot/Q9DCK3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Forms a complex with integrins.|||Membrane http://togogenome.org/gene/10090:Tarm1 ^@ http://purl.uniprot.org/uniprot/B6A8R8 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in lung, uterus, lymph nodes, spleen, thymus and bone marrow. Expressed in bone marrow CD11b(+)Gr-1(+) granulocyte precursors and mature neutrophils.|||Interacts with Fc receptor gamma chain FCER1G.|||May act as receptor. Negatively regulates TCR-mediated CD4(+) T cell proliferation and activation, possibly by binding an unknown ligand on the T cell surface. Enhances Toll-like receptor-mediated production of pro-inflammatory cytokines by macrophages and neutrophils.|||N-glycosylated.|||Up-regulated in CD11b(+)Ly6G(+) and CD11b(+)Ly6C(+) neutrophils upon S.typhimurium bacterial infection. Up-regulated in CD11b(+)Ly6C(intermediate)Ly6G(high)MHCI(-) neutrophils and CD11b(+)Ly6C(high)Ly6G(low)MHCII(+) inflammatory monocytes in response to TLR4 ligand lipopolysaccharide (LPS) stimulation. Up-regulated in cultured macrophages and dendritic cells by TLR4 ligand LPS, TLR2-TLR6 ligand MALP-2 (a bacterial lipopeptide from M.fermentans), TLR1-TLR2 ligand Pam3CSK4 (a synthetic bacterial lipopeptide), TLR3 ligand polyinosinic:polycytidylic acid (poly(I:C), a double-stranded RNA synthetic analog) and TLR7 synthetic ligand imiquimod (R-837). http://togogenome.org/gene/10090:Krt76 ^@ http://purl.uniprot.org/uniprot/Q3UV17 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||Probably contributes to terminal cornification.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:H2bc8 ^@ http://purl.uniprot.org/uniprot/Q6ZWY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Sppl2b ^@ http://purl.uniprot.org/uniprot/Q3TD49 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase A22B family.|||Cell membrane|||Endosome membrane|||Glycosylated.|||Golgi apparatus membrane|||Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in ITM2B and TNF processing. Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus. May play a role in the regulation of innate and adaptive immunity.|||Lysosome membrane|||Membrane|||Monomer. Homodimer. Interacts with ITM2B and TNF.|||The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP. http://togogenome.org/gene/10090:Or51l14 ^@ http://purl.uniprot.org/uniprot/Q8VGZ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tex12 ^@ http://purl.uniprot.org/uniprot/Q9CR81 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase (PubMed:16968740). Requires SYCP1 in order to be incorporated into the central element (PubMed:16968740).|||Interacts with SYCE2.|||Testis (at protein level) (PubMed:11279525, PubMed:16968740). Detected in ovary (PubMed:16968740). Expressed in both male and female germ cells (PubMed:16968740). http://togogenome.org/gene/10090:Npy1r ^@ http://purl.uniprot.org/uniprot/Q04573|||http://purl.uniprot.org/uniprot/Q3V1K5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for neuropeptide Y and peptide YY.|||The alpha form is highly expressed in the brain, heart, kidney, spleen, skeletal muscle, and lung, whereas the beta receptor mRNA was not detected in these tissues. However, the beta form is expressed in mouse embryonic developmental stage (7 and 11 days), bone marrow cells and several hematopoietic cell lines.|||The beta form is expressed in embryonic developmental stage (7 and 11 days). The beta form is an embryonic and a bone marrow form of NPY1-R, which decreases in the expression during development and differentiation. http://togogenome.org/gene/10090:Mpl ^@ http://purl.uniprot.org/uniprot/A2A9D4|||http://purl.uniprot.org/uniprot/Q08351 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an inhibitor of thrombopoietin signaling by promoting protein down-regulation of full-length isoform Mpl-fl.|||Belongs to the type I cytokine receptor family. Type 1 subfamily.|||Cell membrane|||Cell surface|||Expression in the bone marrow displays diurnal rhythmicity (a circadian rhythm that is synchronized with the day/night cycle).|||Golgi apparatus|||Homodimer. Interacts with ATXN2L.|||Rbm15 regulates the production of isoform Mpl-tr.|||Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production. May represent a regulatory molecule specific for TPO-R-dependent immune responses.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||Ubiquitination at Lys-544 and Lys-564 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination (By similarity). http://togogenome.org/gene/10090:Atp5d ^@ http://purl.uniprot.org/uniprot/D3Z7S4|||http://purl.uniprot.org/uniprot/Q4FK74|||http://purl.uniprot.org/uniprot/Q9D3D9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase epsilon chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP turnover in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Eif4g3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J112|||http://purl.uniprot.org/uniprot/A2AMI2|||http://purl.uniprot.org/uniprot/Q80XI3 ^@ Function|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the eukaryotic initiation factor 4G family.|||Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:35951695). Functional homolog of EIF4G1 (PubMed:35951695).|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Interacts with EIF4A, EIF4E, eIF3 and PABPC1 (PubMed:35951695). Part of a complex with EIF4E (PubMed:35951695). eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (PubMed:35951695). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4G1/EIF4G3 interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2 (By similarity). Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate eIF4E (By similarity). Non-phosphorylated EIF4EBP1 competes with EIF4G1/EIFG3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (By similarity). EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA (By similarity). Interacts with FXR1; promoting translation of FXR1 target mRNAs (PubMed:35951695). http://togogenome.org/gene/10090:Pdss1 ^@ http://purl.uniprot.org/uniprot/Q33DR2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FPP/GGPP synthase family.|||Binds 2 Mg(2+) ions per subunit.|||Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1 subunits.|||Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination of the side chain of ubiquinone (PubMed:16262699). Supplies nona and decaprenyl diphosphate, the precursors for the side chain of the isoprenoid quinones ubiquinone-9 (Q9)and ubiquinone-10 (Q10) respectively (PubMed:16262699). The enzyme adds isopentenyl diphosphate molecules sequentially to farnesyl diphosphate with trans stereochemistry (PubMed:16262699).|||Mitochondrion http://togogenome.org/gene/10090:Fabp2 ^@ http://purl.uniprot.org/uniprot/P55050|||http://purl.uniprot.org/uniprot/Q53YP5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Expressed in the small intestine. Highest expression levels in the proximal ileum.|||FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds saturated long-chain fatty acids with a high affinity, but binds with a lower affinity to unsaturated long-chain fatty acids. FABP2 may also help maintain energy homeostasis by functioning as a lipid sensor.|||Forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior. http://togogenome.org/gene/10090:Or9i1 ^@ http://purl.uniprot.org/uniprot/Q8VG66 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Abcc2 ^@ http://purl.uniprot.org/uniprot/Q8VI47 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates. Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification. Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4. Transports sulfated bile salt such as taurolithocholate sulfate. Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors.|||Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Expressed in liver.|||These mice are healthy and show no phenotypic abnormalities. Mice display hyperbilirubinemia and reduced levels of biliary GSH. http://togogenome.org/gene/10090:Ice1 ^@ http://purl.uniprot.org/uniprot/E9Q286 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ICE1 family.|||Cajal body|||Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (By similarity).|||Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts (via N-terminus domain) with ELL. Interacts (via C-terminus domain) with ICE2 and ZC3H8 (By similarity).|||Nucleus|||The N-termimus domain is necessary and sufficient for its targeting to subnuclear cajal and histone locus bodies. http://togogenome.org/gene/10090:Mrgpre ^@ http://purl.uniprot.org/uniprot/Q4V9R2|||http://purl.uniprot.org/uniprot/Q91ZB7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Membrane|||Orphan receptor. May regulate nociceptor function and/or development, including the sensation or modulation of pain. http://togogenome.org/gene/10090:Pars2 ^@ http://purl.uniprot.org/uniprot/Q8CFI5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Mitochondrion matrix http://togogenome.org/gene/10090:Klf14 ^@ http://purl.uniprot.org/uniprot/Q19A41 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Rsl1d1 ^@ http://purl.uniprot.org/uniprot/Q8BVY0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL1 family. Highly divergent.|||Interacts with ING1 (By similarity). Interacts with KPNA7 and KPNA2 (By similarity).|||Regulates cellular senescence through inhibition of PTEN translation. Acts as a pro-apoptotic regulator in response to DNA damage.|||nucleolus http://togogenome.org/gene/10090:Gba ^@ http://purl.uniprot.org/uniprot/P17439 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 30 family.|||Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose (PubMed:24211208). Plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation (By similarity). Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol (PubMed:24211208). GlcCer containing mono-unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose donors for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4-enine) (By similarity). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide (By similarity). Can also hydrolyze cholesteryl 3-beta-D-glucoside producing glucose and cholesterol (By similarity). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the transfer of galactose between GalCers and cholesterol in vitro, but with lower activity than with GlcCers (By similarity). Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate for hydrolysis, however it is a good xylose donor for transxylosylation activity to form cholesteryl 3-beta-D-xyloside (By similarity).|||Homozygous knockout mice die within 24 hours of birth (PubMed:1594045). They are under weight, respire abnormally and show rapidly progressing cyanosis (PubMed:1594045). Feeding and movement are also decreased in these mice (PubMed:1594045). Macrophages accumulating glucosylceramides in tubular lysosomal deposits are found in liver (in Kupffer cells), bone marrow, spleen and brain (PubMed:1594045). Hematopoietic stem cells conditional knockout of GBA1, leads to widespread and organ-specific dysfunction of immune cells. Thymus shows the earliest alteration with features of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes (PubMed:22665763).|||Inhibited by conduritol B epoxide/CBE.|||Interacts with saposin-C. Interacts with SCARB2. Interacts with TCP1 (By similarity). Interacts with GRN; this interaction prevents aggregation of GBA1-SCARB2 complex via interaction with HSPA1A upon stress (PubMed:27789271).|||Lysosome membrane http://togogenome.org/gene/10090:Ubxn1 ^@ http://purl.uniprot.org/uniprot/Q922Y1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with MAVS; this interaction prevents MAVS oligomerization and thus disrupts the RLR signaling pathway. Interacts with CUL1; this interaction inhibits CUL1-mediated degradation of NF-kappa-B inhibitors. Interacts with BIRC2/c-IAP1; this interaction prevents TNFalpha-stimulated RIP1 ubiquitination and subsequent NF-kappa-B activation. Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B (PubMed:11562482). Interacts with HOMER2 (PubMed:16709668). Interacts directly with VCP. Interacts with BRCA1 and BARD1; interaction takes place when BRCA1 is not autoubiquitinated but is strongly enhanced in the presence of autoubiquitinated BRCA1.|||The UBA domain specifically recognizes and binds 'Lys-6'-linked polyubiquitin chains.|||Ubiquitin-binding protein that plays a role in the modulation of innate immune response. Blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, UBXN1 is induced and recruited to the RLR component MAVS. In turn, interferes with MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. This function probably serves as a brake to prevent excessive RLR signaling. Interferes with the TNFalpha-triggered NF-kappa-B pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs) and thereby inhibiting their recruitment to TNFR1. Prevents also the activation of NF-kappa-B by associating with CUL1 and thus inhibiting NF-kappa-B inhibitor alpha/NFKBIA degradation that remains bound to NF-kappa-B. Interacts with the BRCA1-BARD1 heterodimer and regulates its activity. Specifically binds 'Lys-6'-linked polyubiquitin chains. Interaction with autoubiquitinated BRCA1 leads to the inhibition of the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer. Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. http://togogenome.org/gene/10090:Shisa6 ^@ http://purl.uniprot.org/uniprot/Q3UH99 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Barely detectable in the brain of embryonic day 17 (17 dpc). Expressed in hippocampus and septum from postnatal day 1 (P1) and then in cerebellum and olfactory bulb from postnatal day 7 (P7).|||Belongs to the shisa family.|||Component of the postsynaptic hippocampal AMPA-type glutamate receptor (AMPAR) complex, at least composed of pore forming AMPAR subunits GRIA1, GRIA2 and GRIA3 and AMPAR auxiliary proteins SHISA6 and SHISA7 (PubMed:26931375, PubMed:29199957). Interacts (via PDZ-binding motif) with DLG4/PSD-95 (via PDZ domain); the interaction is direct (PubMed:26931375).|||Decreases decay times of miniature excitatory postsynaptic currents (mEPSCs) and light-induced AMPA-type glutamate receptor (AMPAR) currents in CA1 pyramidal cell.|||Highly expressed in cerebellum and hippocampal neurons: CA1 stratum oriens and stratum radiatum, CA3 stratum oriens and stratum lucidum, and the dentate gyrus polymorphic layer (PubMed:26931375). Expressed in other brain structures including olfactory bulb, cortex, amygdala and midbrain (at protein level) (PubMed:26623514, PubMed:26931375). Also expressed in a subset of spermatogonial stem cells (PubMed:28196692). Also expressed in eye, heart, kidney, lung, muscle and spleen. Isoform 2: Specifically expressed in hippocampus (PubMed:26931375).|||Involved in maintenance of high-frequency synaptic transmission at hippocampal CA3-CA1 synapses. Regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (PubMed:26931375). May play a role in self-renewal and differentiation of spermatogonial stem cells by inhibiting canonical Wnt signaling pathway (PubMed:28196692).|||N-glycosylated.|||Postsynaptic density membrane|||The PDZ-binding motif interacts with PDZ-domain of scaffolding protein DLG4. http://togogenome.org/gene/10090:Kcnip3 ^@ http://purl.uniprot.org/uniprot/Q9QXT8 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the recoverin family.|||Binds to DNA as a homomultimer. Dimerization is induced by binding to calcium (PubMed:18201103). Interacts with the C-terminus of PSEN1 and PSEN2 and with PSEN2 CTF subunit. Associates with KCN1. Component of heteromultimeric potassium channels (PubMed:19713751). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). Interacts with KCND2 and KCND3 (PubMed:11598014, PubMed:12451113, PubMed:20943905).|||Calcium-dependent transcriptional repressor that binds to the DRE element of genes including PDYN and FOS. Affinity for DNA is reduced upon binding to calcium and enhanced by binding to magnesium. Seems to be involved in nociception.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||Golgi apparatus|||Highly expressed in brain. Isoform 1 or isoform 4 (T+ forms) are expressed at equal levels with isoform 2 or isoform 3 (T- forms). Primarily detected in the layer V and deep layer VI of the cerebral cortex, the hippocampus, and the entire cerebellum. Expressed at low levels in testis. Also expressed in heart.|||Lacks EF-hand domains.|||May play a role in the regulation of PSEN2 proteolytic processing and apoptosis. Together with PSEN2 involved in modulation of amyloid-beta formation (By similarity).|||Mice deficient for Csen show a significant decrease of amyloid-beta protein 40 and beta-amyloid protein 42, and display markedly reduced responses in models of acute thermal, mechanical, and visceral pain.|||Nucleus|||Palmitoylated. Palmitoylation enhances association with the plasma membrane (By similarity).|||Proteolytically cleaved by caspase-3.|||Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels, such as KCND2/Kv4.2 and KCND3/Kv4.3. Modulates channel expression at the cell membrane, gating characteristics, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner. http://togogenome.org/gene/10090:Batf2 ^@ http://purl.uniprot.org/uniprot/Q8R1H8 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system. Selectively suppresses CCN1 transcription and hence blocks the downstream cell proliferation signals produced by CCN1 and inhibits CCN1-induced anchorage-independent growth and invasion in several cancer types. Possibly acts by interfering with AP-1 binding to CCN1 promoter (By similarity). Following infection, participates in the differentiation of CD8(+) thymic conventional dendritic cells in the immune system. Acts via the formation of a heterodimer with JUN family proteins that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3' and regulates expression of target genes.|||Belongs to the bZIP family.|||By cytokines in response to infection. By IFN-gamma.|||Heterodimer; heterodimerizes with JUN family proteins.|||Mice display normal development of natural killer (NK), T- and B-cells, plasmacytoid dendritic cells (pDCs), neutrophils, resting CD8-alpha(+) classical dendritic cells (cDCs), and peritoneal, liver and lung macrophages. However, they show significantly decreased survival after infection by T.gondii. Notably, mice show significantly decreased numbers of lung-resident CD103(+)CD11b(-) dendritic cells and CD103(+)CD11b(-) macrophages after infection.|||Nucleus http://togogenome.org/gene/10090:Cct6a ^@ http://purl.uniprot.org/uniprot/P80317|||http://purl.uniprot.org/uniprot/Q3TI05|||http://purl.uniprot.org/uniprot/Q52KG9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG.|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||Expressed in all tissues examined.|||The N-terminus is blocked. http://togogenome.org/gene/10090:Gria3 ^@ http://purl.uniprot.org/uniprot/B0QZW1|||http://purl.uniprot.org/uniprot/Q0VGS8|||http://purl.uniprot.org/uniprot/Q9Z2W9 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA3 subfamily.|||Cell membrane|||Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with PRKCABP, GRIP1 and GRIP2 (By similarity). Found in a complex with GRIA1, GRIA2, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 (By similarity).|||Membrane|||Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-615 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-841 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.|||Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (By similarity).|||The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.|||The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate. http://togogenome.org/gene/10090:Rangrf ^@ http://purl.uniprot.org/uniprot/Q9JIB0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MOG1 family.|||Cell membrane|||Cytoplasm|||Down-regulated in mice lacking Ovol1.|||Highgly abundant in cardiac cells. Expressed in testis during prepubertal development.|||May regulate the intracellular trafficking of RAN (PubMed:10811801, PubMed:11733047). Promotes guanine nucleotide release from RAN and inhibits binding of new GTP by preventing the binding of the RAN guanine nucleotide exchange factor RCC1 (PubMed:10811801, PubMed:11733047). Regulates the levels of GTP-bound RAN in the nucleus, and thereby plays a role in the regulation of RAN-dependent mitotic spindle dynamics (By similarity). Enhances the expression of SCN5A at the cell membrane in cardiomyocytes (PubMed:18184654, PubMed:23420830).|||Monomer (Probable). Interacts with RAN, both RAN-GTP and RAN-GDP (PubMed:10811801). Competes with RCC1 for a common binding site on RAN and thereby inhibits RCC1-mediated nucleotide exchange (By similarity). Forms a complex with RAN-GTP and RANBP1 (PubMed:10811801). Interacts with the cytoplasmic loop 2 of SCN5A (PubMed:18184654).|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Anxa2 ^@ http://purl.uniprot.org/uniprot/P07356|||http://purl.uniprot.org/uniprot/Q542G9 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Animals show a 40% increase of LDL-cholesterol levels in plasma.|||Belongs to the annexin family.|||Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response (By similarity). Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:22848640).|||Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36 (By similarity). Interacts with ATP1B1 (By similarity). Interacts with DYSF (PubMed:14506282). Interacts with COCH. Interacts (via repeat Annexin 1) with PCSK9 (via the C-terminal domain); the interaction inhibits the degradation of LDLR. Interacts with CEACAM1 (via the cytoplasmic domain); this interaction is regulated by phosphorylation of CEACAM1 (By similarity). Interacts with APPL2 and APPL1; targets APPL2 to endosomes and acting in parallel to RAB5A (PubMed:21645192). Interacts with S100A4 (By similarity). May interact with UBAP2 (By similarity).|||ISGylated.|||It may cross-link plasma membrane phospholipids with actin and the cytoskeleton and be involved with exocytosis.|||Melanosome|||Membrane|||basement membrane http://togogenome.org/gene/10090:Slc24a3 ^@ http://purl.uniprot.org/uniprot/Q8VD29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.|||Membrane http://togogenome.org/gene/10090:Tsga8 ^@ http://purl.uniprot.org/uniprot/Q9JJL0 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Detected in testis from 18 days onwards. In developing spermatazoa, expressed from the round spermatid stage through to the terminal stages of spermiogenesis, when expression declines.|||Specifically expressed in testis (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Or1a1b ^@ http://purl.uniprot.org/uniprot/Q7TRX1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Insc ^@ http://purl.uniprot.org/uniprot/Q3HNM7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed at 12.5 dpc in dorsal root and cranial glanglia in the developing brain. Detected at 14.5 dpc in skin epidermis (at protein level). First detected at 10.5 dpc in the dorsal root glanglia and cranial glanglia. At 12.5 dpc expression appears in retina, forebrain and outside of the nervous system. At 13.5 dpc a strong expression is detected in the cortex. Expressed in embryonic, newborn and adult skin.|||Expressed in brain, kidney, liver, testis and skin.|||Interacts with ALS2CR19/PAR3B and GPSM1/AGS3 (By similarity). Interacts with F2RL2/PAR3 (PubMed:16094321). Interacts with GPSM2/LGN (via TPR repeat region) (PubMed:16094321, PubMed:21816348).|||May function as an adapter linking the Par3 complex to the GPSM1/GPSM2 complex. Involved in spindle orientation during mitosis (PubMed:16301171, PubMed:21816348). May regulate cell proliferation and differentiation in the developing nervous system (PubMed:16301171). May play a role in the asymmetric division of fibroblasts and participate in the process of stratification of the squamous epithelium (PubMed:16094321).|||cell cortex http://togogenome.org/gene/10090:Idua ^@ http://purl.uniprot.org/uniprot/Q3U1Z0|||http://purl.uniprot.org/uniprot/Q8BLF6|||http://purl.uniprot.org/uniprot/Q8BMG0 ^@ Similarity ^@ Belongs to the glycosyl hydrolase 39 family. http://togogenome.org/gene/10090:Tnfsf8 ^@ http://purl.uniprot.org/uniprot/P32972|||http://purl.uniprot.org/uniprot/Q544U1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cytokine that binds to TNFRSF8/CD30. Induces proliferation of T-cells.|||Homotrimer.|||Membrane http://togogenome.org/gene/10090:Or4k77 ^@ http://purl.uniprot.org/uniprot/Q7TQY4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bhlhe23 ^@ http://purl.uniprot.org/uniprot/Q8BGW3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Disrupted rod signaling and profound retinal dysfunction.|||Expressed in brain and retina.|||Expression is confined to regions of the developing nervous system and pancreas. At 13 dpc expressed at lower levels in the trigeminal ganglion, the ganglionic eminence, the ventral neural tube, and dorsal root ganglia. Expressed at moderate levels in the tectum of the embryonic midbrain. Most prominent expression is in the diencephalon, where it flanks either side of the roof of the third ventricle, dorsal/caudal to the dorsal thalamus. Detected in the pancreas during the time when most of the pancreatic endocrine cell types are beginning to differentiate and endocrine precursor cells remain loosely associated with the duct epithelium until they begin to form aggregates late in development.|||May function as transcriptional repressor. May modulate the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types. May be important for rod bipolar cell maturation.|||Nucleus http://togogenome.org/gene/10090:Thra ^@ http://purl.uniprot.org/uniprot/P63058 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Binds DNA as a dimer; homodimer and heterodimer with RXRB. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Probably interacts with SFPQ. Interacts with AKAP13. Interacts with C1D. Interacts with TP53INP2. Interacts with PER2. Isoform alpha-2 and isoform alpha-1 interact with TACC1, but the interaction with alpha-1 is much weaker. The interaction with isoform alpha-1, but not alpha-2, is decreased in the presence of thyroid hormone T3 (PubMed:20078863).|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. Isoform Alpha-deltaE6 lacks the hinge region that connects the modulating domain and the DNA binding domain.|||Cytoplasm|||Does not bind thyroid hormone T3.|||Due to mismatches with the underlying genomic sequence that lie within a microexon, this isoform has been proposed to undergo RNA editing involving both base insertion and deletion.|||Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Isoform Alpha-deltaE6 does not bind DNA, inhibits the activity of isoform Alpha-1, and stimulates myoblast differentiation.|||Nucleus|||Ubiquitous (Isoform Alpha-deltaE6). http://togogenome.org/gene/10090:Bloc1s5 ^@ http://purl.uniprot.org/uniprot/Q8R015 ^@ Disease Annotation|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the BLOC1S5 family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking.|||Defects in Muted are the cause of the Muted (mu) mutant, which is characterized by light eyes at birth, hypopigmentation of the coat, platelet storage pool deficiency and lysosomal hyposecretion.|||Detected in heart, brain, spleen, lung, kidney and testis.|||Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. Interacts with BLOC1S4, BLOC1S6, DTNBP1/BLOC1S7 and PI4K2A. http://togogenome.org/gene/10090:Lipo4 ^@ http://purl.uniprot.org/uniprot/F6RR30 ^@ Similarity ^@ Belongs to the AB hydrolase superfamily. Lipase family. http://togogenome.org/gene/10090:Or8b37 ^@ http://purl.uniprot.org/uniprot/Q7TRE1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cnot4 ^@ http://purl.uniprot.org/uniprot/Q8BT14 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated.|||Cytoplasm|||Has E3 ubiquitin ligase activity, promoting ubiquitination and degradation of target proteins. Involved in activation of the JAK/STAT pathway. Catalyzes ubiquitination of methylated RBM15. Plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA. As part of the PINK1-regulated signaling, upon mitochondria damage, ubiquitinates ABCE1 and thereby recruits autophagy receptors to the mitochondrial outer membrane to initiate mitophagy.|||Interacts with CNOT1 via its C-terminus but does not stably associate with the CCR4-NOT complex. Interacts (via RING domain) with UBE2D2. Interacts with ABCE1, PINK1 and PELO.|||Nucleus http://togogenome.org/gene/10090:Myl6 ^@ http://purl.uniprot.org/uniprot/Q60605 ^@ Function|||Subunit ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains. Interacts with SPATA6 (PubMed:25605924).|||Regulatory light chain of myosin. Does not bind calcium. http://togogenome.org/gene/10090:Ctbp1 ^@ http://purl.uniprot.org/uniprot/A0A0J9YU62|||http://purl.uniprot.org/uniprot/O88712 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated; when cells are exposed to brefeldin A.|||Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.|||Cofactor binding induces a conformational change.|||Corepressor targeting diverse transcription regulators such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Functions in brown adipose tissue (BAT) differentiation.|||Cytoplasm|||Expressed in a wide range of adult tissues.|||Expressed throughout the developmental stages.|||Homo- or heterodimer. Heterodimer with CTBP2. Interacts with ELK3 (via its PXDLS motif). Interacts with RBBP8 (via its PXDLS motif). Interacts with PNN, MECOM and ZFHX1B. Interacts with ZNF366 (via PXDLS motif) (By similarity). Interaction with SATB1 (non-acetylated form); the interaction stabilizes its attachment to DNA and promotes transcription repression. Interacts with PRDM16; the interaction represses white adipose tissue (WAT)-specific genes expression. Interacts with GLIS2, HIPK2, FOXP1, FOXP2, HDAC4, HDAC5, HDAC9, NRIP1, WIZ and ZNF217. Interacts with BCL6; the interaction is required for BCL6 transcriptional autoinhibition and inhibition of some BCL6 target genes. Interacts with IKZF4. Interacts with MCRIP1 (unphosphorylated form, via the PXDLS motif); competitively inhibiting CTBP-ZEB1 interaction (By similarity). Interacts with Bassoon/BSN; this interaction targets and anchors CTBP1 to presynapses (By similarity). Interacts with SIMC1 (By similarity).|||Nucleus|||Sumoylation on Lys-429 is promoted by the E3 SUMO-protein ligase CBX4.|||The level of phosphorylation appears to be regulated during the cell cycle. Phosphorylation by HIPK2 on Ser-423 induces proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Vps13b ^@ http://purl.uniprot.org/uniprot/Q80TY5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VPS13 family.|||Early endosome membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Interacts with STX6 (PubMed:30962439). Interacts with STX12 (via N-terminus) (PubMed:30962439). Interacts with RAB6A isoform 1 (GTP-bound) and isoform 2 (GTP-bound) (By similarity). Interacts with RAB6B (GTP-bound) (By similarity).|||Lysosome membrane|||Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phosphatidylinositol 3-phosphate (PubMed:30962439). Functions as a tethering factor in the slow endocytic recycling pathway, to assist traffic between early and recycling endosomes (By similarity). Involved in the transport of proacrosomal vesicles to the nuclear dense lamina (NDL) during spermatid development (PubMed:31218450). Plays a role in the assembly of the Golgi apparatus, possibly by mediating trafficking to the Golgi membrane (By similarity). Plays a role in the development of the nervous system, and may be required for neuron projection development (PubMed:31495077). May also play a role during adipose tissue development (By similarity). Required for maintenance of the ocular lens (PubMed:32915983). Required for proper organization of the Golgi (By similarity).|||Recycling endosome membrane|||Ubiquitously expressed in all examined tissues.|||acrosome membrane|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Prmt7 ^@ http://purl.uniprot.org/uniprot/Q922X9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Specifically mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s. Plays a role in gene imprinting by being recruited by CTCFL at the H19 imprinted control region (ICR) and methylating histone H4 to form H4R3me2s, possibly leading to recruit DNA methyltransferases at these sites. May also play a role in embryonic stem cell (ESC) pluripotency. Also able to mediate the arginine methylation of histone H2A and myelin basic protein (MBP) in vitro; the relevance of such results is however unclear in vivo (By similarity).|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT7 subfamily.|||Homodimer and heterodimer. Interacts with PRMT5 and SNRPD3 (By similarity). Interacts with CTCFL.|||Mutants, shortly after birth, display significant reduced body size, reduced weight and shortened fifth metatarsals. They are subviable with about 45% of the expected number of mutant pups at P14. Surviving adult mice exhibit increased fat mass, reduced length and limb abnormalities. They also have reduced bone mineral content and density. Knockout mice show sexually dimorphic phenotypes, including changes in bone mineral content, bone mineral density and fifth metacarpal length that are only significant in females.|||Nucleus|||Present in undifferentiated embryonic stem and germ cells; expression is lost when cells differentiate. In the developing testis, it is expressed at all stages. Present in all cells within the developing tubule, including gonocytes and spermatogonia (at protein level). It the developing kidney, it is confined to the nephrogenic zone in the cortical region, where the tips of the ureteric bud induce de novo formation of epithelia in the metanephric mesenchyme and early glomeruli. Expression is around 8-fold lower in adult kidneys.|||cytosol http://togogenome.org/gene/10090:Ptrhd1 ^@ http://purl.uniprot.org/uniprot/D3Z4S3 ^@ Similarity ^@ Belongs to the PTH2 family. PTRHD1 subfamily. http://togogenome.org/gene/10090:Il17rd ^@ http://purl.uniprot.org/uniprot/Q8JZL1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||During early embryogenesis, predominantly expressed at 6.5 dpc and 9.5 dpc in the forebrain, mid-hindbrain boundary, branchial arches, somites, limb bud and tailbud. At 12.5 dpc additionally expressed in the diencephalon, optic stalk, pituitary, olfactory and oral epithelium, tooth primordia, somites, developing metanephric kidney and stomach. Expressed in the neopallial cortex, rhombic lip and dorsal regions of the myelencephalon and in the frontal nasal process. Expressed in the commissural plate and septal area of the forebrain and in the hippocampus, lens and optic cup. In the oral region, expressed in the tongue and in the mesenchyme of the first branchial arch. Also expressed in the developing inner ear. Expression patterns remain essentially unchanged at 15.5 dpc, with the addition of a strong expression in the submandibular gland.|||Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation (PubMed:12604616). Regulates the nuclear ERK signaling pathway by spatially blocking nuclear translocation of activated ERK (By similarity). Mediates JNK activation and may be involved in apoptosis (PubMed:15277532). May inhibit FGF-induced FGFR1 tyrosine phosphorylation (PubMed:12604616). Might have a role in the early stages of fate specification of GnRH-secreting neurons (PubMed:23643382). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (PubMed:25576668).|||Golgi apparatus membrane|||Self-associates. Interacts with FGFR2 and phosphorylated MAP2K1 or MAP2K2. Associates with a MAP2K1/2-MAPK1/3 complex (By similarity). Interacts with FGFR1 and MAP3K7. http://togogenome.org/gene/10090:Mapk1 ^@ http://purl.uniprot.org/uniprot/P63085 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Binds both upstream activators and downstream substrates in multimolecular complexes. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, NISCH, SGK1, and isoform 1 of NEK2. Interacts (via phosphorylated form) with TPR (via C-terminal region and phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation (By similarity). Interacts with MAP2K1 (By similarity). Interacts with DUSP6 (By similarity). Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with DCC (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with PEA15 (PubMed:16162500). Interacts with MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (PubMed:11702783). The phosphorylated form interacts with PML. Interacts with STYX. Interacts with CDK2AP2. Interacts with CAVIN4 (By similarity). Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity (PubMed:27783954). Interacts with GIT1; this interaction is necessary for MAPK1 localization to focal adhesions (PubMed:15923189). Interacts with ZNF263 (By similarity).|||Cytoplasm|||Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity). Phosphorylated upon FLT3 and KIT signaling (By similarity). Dephosphorylated by DUSP1 and DUSP2 at Thr-183 and Tyr-185 (By similarity) (PubMed:8221888).|||ISGylated.|||Nucleus|||Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.|||Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination; leading to activation. Deubiquitinated by CYLD.|||Widely expressed.|||caveola|||centrosome|||focal adhesion|||spindle http://togogenome.org/gene/10090:Cd8a ^@ http://purl.uniprot.org/uniprot/P01731|||http://purl.uniprot.org/uniprot/Q8CAX3 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cd8a-deficient mice prevent the development of class I MHC restricted cytotoxic T-cells. However, maturation of class II MHC restricted T-helper cells seems to be unaffected by the absence of Cd8a.|||Cell membrane|||Forms disulfide-linked heterodimers with CD8B at the cell surface. Forms also homodimers in several cell types including NK-cells or peripheral blood T-lymphocytes. Interacts with the MHC class I HLA-A/B2M dimer. Interacts with LCK in a zinc-dependent manner.|||Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells.|||Membrane|||Palmitoylated, but association with CD8B seems to be more important for the enrichment of CdD8A in lipid rafts.|||Phosphorylated in cytotoxic T-lymphocytes (CTLs) following activation. http://togogenome.org/gene/10090:Rasgrp2 ^@ http://purl.uniprot.org/uniprot/Q9QUG9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RASGRP family.|||Cell membrane|||Detected in megakaryocytes, platelet and neutrophils but not in lymphocytes (at protein level). Isoform 1 and isoform 3 are detected in brain basal glanglia, heart, lung, spleen, liver and kidney interstitial cells.|||Expressed in embryo with higher expression between 15 dpc and 17 dpc.|||Forms a signaling complex with RAP1 and BRAF. Interacts with F-actin (By similarity). Interacts with RAP1.|||Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activate other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.|||Mice have a combination of defects in leukocytes and platelet functions which are reminiscent of the human leukocyte adhesion deficiency type III syndrome (LAD3). They display bleeding diathesis due to a defect in platelet aggregation and are resistant to collagen-induced thrombosis. In parallel, they also display impaired response to acute inflammation associated with defects in beta-1 and beta-2 integrin-mediated adhesion of neutrophils.|||The N-terminal Ras-GEF domain mediates association with F-actin.|||The corresponding protein is not undetectable.|||cytosol|||ruffle membrane|||synaptosome http://togogenome.org/gene/10090:Tbcd ^@ http://purl.uniprot.org/uniprot/Q8BYA0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TBCD family.|||Cytoplasm|||Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with PPP2CB (By similarity). Part of a supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state. Interacts with ARL2; interaction is enhanced with the GDP-bound form of ARL2. Does not interact with ARL3, ARL4A and ARL4D. Interacts with beta tubulin. Interacts with TBCE (By similarity).|||Lateral cell membrane|||Tubulin-folding protein implicated in the first step of the tubulin folding pathway and required for tubulin complex assembly. Involved in the regulation of microtubule polymerization or depolymerization, it modulates microtubule dynamics by capturing GTP-bound beta-tubulin (TUBB). Its ability to interact with beta tubulin is regulated via its interaction with ARL2. Acts as a GTPase-activating protein (GAP) for ARL2. Induces microtubule disruption in absence of ARL2. Increases degradation of beta tubulin, when overexpressed in polarized cells. Promotes epithelial cell detachment, a process antagonized by ARL2. Induces tight adherens and tight junctions disassembly at the lateral cell membrane. Required for correct assembly and maintenance of the mitotic spindle, and proper progression of mitosis. Involved in neuron morphogenesis.|||adherens junction|||centrosome|||tight junction http://togogenome.org/gene/10090:Ddx11 ^@ http://purl.uniprot.org/uniprot/Q6AXC6 ^@ Cofactor|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Aberrant splicing.|||Associates with the CTF18-RFC complex. Associates with a cohesin complex composed of RAD21, SMC1 proteins and SMC3. Interacts with CHTF18. Interacts with DSCC1. Interacts with FEN1; this interaction is direct and increases flap endonuclease activity of FEN1. Interacts with PCNA. Interacts with POLR1A and UBTF. Interacts with RAD21, SMC1 proteins and SMC3. Interacts with RFC2. Interacts with TIMELESS; this interaction increases recruitment of both proteins onto chromatin in response to replication stress induction by hydroxyurea.|||Belongs to the DEAD box helicase family. DEAH subfamily. DDX11/CHL1 sub-subfamily.|||Binds 1 [4Fe-4S] cluster.|||DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis. Its double-stranded DNA helicase activity requires either a minimal 5'-single-stranded tail length of approximately 15 nt (flap substrates) or 10 nt length single-stranded gapped DNA substrates of a partial duplex DNA structure for helicase loading and translocation along DNA in a 5' to 3' direction. The helicase activity is capable of displacing duplex regions up to 100 bp, which can be extended up to 500 bp by the replication protein A (RPA) or the cohesion CTF18-replication factor C (Ctf18-RFC) complex activities. Shows also ATPase- and helicase activities on substrates that mimic key DNA intermediates of replication, repair and homologous recombination reactions, including forked duplex, anti-parallel G-quadruplex and three-stranded D-loop DNA molecules. Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage. Recruited with TIMELESS factor upon DNA-replication stress response at DNA replication fork to preserve replication fork progression, and hence ensure DNA replication fidelity (By similarity). Cooperates also with TIMELESS factor during DNA replication to regulate proper sister chromatid cohesion and mitotic chromosome segregation (PubMed:17611414). Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner; and hence it may contribute in Okazaki fragment processing at DNA replication fork during lagging strand DNA synthesis. Its ability to function at DNA replication fork is modulated by its binding to long non-coding RNA (lncRNA) cohesion regulator non-coding RNA DDX11-AS1/CONCR, which is able to increase both DDX11 ATPase activity and binding to DNA replicating regions (By similarity). Plays also a role in heterochromatin organization (PubMed:21854770). Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (By similarity). Plays a role in embryonic development and prevention of aneuploidy (PubMed:17611414). Involved in melanoma cell proliferation and survival. Associates with chromatin at DNA replication fork regions. Binds to single- and double-stranded DNAs (By similarity).|||Embryonic death at 10.5 dpc (PubMed:17611414). Embryos are smaller in size, malformed and exhibit sparse cellularity in comparison to normal or heterozygous litter mates (PubMed:17611414). Show inability to form a proper embryonic placenta. Display high incidence of cell aneuploidy due to abnormal chromosomal segregation (PubMed:17611414). Show abnormal formation and localization of heterochromatin (PubMed:21854770).|||Midbody|||Nucleus|||centrosome|||nucleolus|||spindle pole http://togogenome.org/gene/10090:Vmn2r109 ^@ http://purl.uniprot.org/uniprot/K7N747 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mup18 ^@ http://purl.uniprot.org/uniprot/A2BIM8|||http://purl.uniprot.org/uniprot/P04938 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Major urinary proteins (Mups) bind pheromones, and thus stabilize them to allow slow release into the air from urine marks. May protect pheromones from oxidation. May also act as pheromones themselves. In this context, they play a role in the regulation of social behaviors, such as aggression, mating, pup-suckling, territory establishment and dominance (Probable). Binds the pheromone analog 2-sec-butyl-4,5-dihydrothiazole (SBT) in vitro (PubMed:25279835).|||Major urinary proteins (Mups) bind pheromones, and thus stabilize them to allow slow release into the air from urine marks. May protect pheromones from oxidation. May also act as pheromones themselves. In this context, they play a role in the regulation of social behaviors, such as aggression, mating, pup-suckling, territory establishment and dominance.|||Secreted http://togogenome.org/gene/10090:Or4d10b ^@ http://purl.uniprot.org/uniprot/Q8VFV1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tssk6 ^@ http://purl.uniprot.org/uniprot/Q925K9 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Expressed in the testis, localized to the heads of elongating spermatids.|||Interacts with HSP90; this interaction stabilizes and activates TSSK6 (PubMed:23599433). Interacts with the heat shock proteins HSPCB, HSPA8 and HSPA1A. These interactions appear to be required for TSSK6 kinase activity. Interacts with TSACC; this interaction is direct and recruits TSACC to HSP90, which is essential for kinase activity (By similarity).|||Mg(2+) and Mn(2+) were both present in the kinase buffer but Mg(2+) is likely to be the in vivo cofactor.|||Mice are sterile due to profound impairment in motility and morphology of spermatozoa.|||Required for sperm production and function. Plays a role in DNA condensation during postmeiotic chromatin remodeling.|||Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation. http://togogenome.org/gene/10090:Krtap3-2 ^@ http://purl.uniprot.org/uniprot/Q9D638 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 3 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).|||Interacts with hair keratins. http://togogenome.org/gene/10090:Vmn2r107 ^@ http://purl.uniprot.org/uniprot/E9PZJ7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pard3b ^@ http://purl.uniprot.org/uniprot/Q9CSB4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PAR3 family.|||Cell junction|||Endomembrane system|||Interacts with PARD6B. Interacts with INSC/inscuteable (By similarity).|||Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions (By similarity).|||Sequence incomplete.|||tight junction http://togogenome.org/gene/10090:Cd209e ^@ http://purl.uniprot.org/uniprot/Q91ZW7 ^@ Caution|||Function|||Subcellular Location Annotation ^@ In mouse, 5 genes homologous to human CD209/DC-SIGN and CD209L/DC-SIGNR have been identified.|||Membrane|||Putative pathogen-recognition receptor. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. http://togogenome.org/gene/10090:Enpp2 ^@ http://purl.uniprot.org/uniprot/G3UXY9|||http://purl.uniprot.org/uniprot/Q9R1E6 ^@ Activity Regulation|||Cofactor|||Disease Annotation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 2 Zn(2+) ions per subunit.|||Expressed in brain and adipose tissue.|||Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:17208043, PubMed:28414242, PubMed:27780639). Major substrate is lysophosphatidylcholine (PubMed:17208043, PubMed:27780639). Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:18175805). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition (By similarity). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor. Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (By similarity). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (By similarity).|||Inhibited by EDTA and EGTA.|||May contribute to obesity (PubMed:15700135).|||N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity. Secretion requires simultaneous glycosylation on Asn-53 and Asn-410, while probable glycosylation of Asn-410 has a preferential role on lysoPLD activity. Not O-glycosylated.|||Secreted|||The interdomain disulfide bond between Cys-413 and Cys-805 is essential for catalytic activity.|||Up-regulated in adipocytes of obese-diabetic db/db mice. http://togogenome.org/gene/10090:Scgb3a1 ^@ http://purl.uniprot.org/uniprot/Q920D7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the secretoglobin family. UGRP subfamily.|||Detected in lung at embryonic stage 18.5 dpc. During gestation, expressed in the mammary gland from 6.5 dpc with highest expression at 10.5 dpc. Expression then declines, but later increases again during mammary gland involution at 4-21 days post partum.|||Highly expressed in lung, where it localizes to epithelial cells lining the trachea and bronchi (PubMed:12406855, PubMed:12175512). Expression in lung is mainly restricted to bronchi, submucosal glands of the trachea, and tracheal epithelium, with little expression in terminal bronchioles (PubMed:12406855). Expressed in uterus where it localizes to epithelial cells of the uterine glands (PubMed:12175512). Also detected in heart, stomach and small intestine (PubMed:12175512).|||Homodimer; disulfide-linked.|||Secreted|||Secreted cytokine-like protein. Inhibits cell growth in vitro. http://togogenome.org/gene/10090:Cldn34b2 ^@ http://purl.uniprot.org/uniprot/Q9D9N2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Smg6 ^@ http://purl.uniprot.org/uniprot/P61406 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. May have a general role in telomere regulation. Promotes in vitro the ability of TERT to elongate telomeres. Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization. Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER).|||May form homooligomers. Associated component of the telomerase holoenzyme complex. Interacts with TERT, independently of the telomerase RNA. Interacts with SMG1, SMG5, SMG7, UPF1, UPF2, UPF3B and the PP2A catalytic subunits. Also interacts with the exon junction complex (EJC) composed at least of CASC3, EIF4A3, MAGOH and RBM8A; required for the process of nonsense-mediated mRNA decay. Interacts with DHX34; the interaction is RNA-independent (By similarity).|||Plays a role in nonsense-mediated mRNA decay. Is thought to provide a link to the mRNA degradation machinery as it has endonuclease activity required to initiate NMD, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Degrades single-stranded RNA (ssRNA), but not ssDNA or dsRNA.|||The PINc domain confers endonuclease activity and is expected to bind the catalytic metal ion.|||cytosol|||nucleolus|||telomere http://togogenome.org/gene/10090:Uts2r ^@ http://purl.uniprot.org/uniprot/Q05AD1|||http://purl.uniprot.org/uniprot/Q8VIH9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system (By similarity).|||High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system.|||Membrane http://togogenome.org/gene/10090:Stfa3 ^@ http://purl.uniprot.org/uniprot/P35173 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cystatin family.|||Cytoplasm|||This is an intracellular thiol proteinase inhibitor. http://togogenome.org/gene/10090:Adcy9 ^@ http://purl.uniprot.org/uniprot/E9Q706|||http://purl.uniprot.org/uniprot/P51830 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors. Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and by beta-adrenergic receptors.|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Cell membrane|||Detected in brain, spleen, lung, liver and testis (at protein level). Detected in brain, especially in hippocampus, cerebellum and neocortex. Found in decreasing order in skeletal muscle, heart, adrenal gland, ovary and brain; and to a lesser extent, in kidney, liver, testis, lung, thymus and spleen.|||Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation. Activity is down-regulated by calcium/calcineurin.|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. http://togogenome.org/gene/10090:Klk1b5 ^@ http://purl.uniprot.org/uniprot/P15945 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Akap11 ^@ http://purl.uniprot.org/uniprot/Q8BSJ2 ^@ Similarity ^@ Belongs to the AKAP110 family. http://togogenome.org/gene/10090:Gas1 ^@ http://purl.uniprot.org/uniprot/Q01721 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Specific growth arrest protein involved in growth suppression. Blocks entry to S phase. Prevents cycling of normal and transformed cells. http://togogenome.org/gene/10090:Gm20907 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Daxx ^@ http://purl.uniprot.org/uniprot/O35613|||http://purl.uniprot.org/uniprot/Q3UKR0 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DAXX family.|||Cytoplasm|||Expressed as early as 12.5 dpc in the neuroepithelium (ventricular zone). At 17.5 dpc, expression becomes more pronounced in postmitotic cells of the cortical plate (CP). Early postnatally (postnatal day 2 [P2]) and in the adult brain (P30) expressed both in the cortex and in the hippocampus.|||Homomultimer. Interacts (via C-terminus) with TNFRSF6 (via death domain). Interacts with PAX5, SLC2A4/GLUT4, MAP3K5, TGFBR2, phosphorylated dimeric HSPB1/HSP27, CENPC, ETS1, sumoylated PML, UBE2I, MCRS1 and TP53. Interacts (via N-terminus) with HIPK2 and HIPK3. Interacts with HIPK1, which induces translocation from PML/POD/ND10 nuclear bodies to chromatin and enhances association with HDAC1. Interacts (non-phosphorylated) with PAX3, PAX7, DEK, HDAC1, HDAC2, HDAC3, acetylated histone H4 and histones H2A, H2B, H3, H3.3 and H4. Interacts with SPOP; mediating CUL3-dependent proteasomal degradation. Interacts with CBP; the interaction is dependent the sumoylation of CBP and suppresses CBP transcriptional activity via recruitment of HDAC2 directly in the complex with TP53 and HIPK2. Interacts with AXIN1; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 on and induces cell death on UV irradiation. Interacts with MDM2; the interaction is direct. Interacts with USP7; the interaction is direct and independent of MDM2 and TP53. Part of a complex with DAXX, MDM2 and USP7 under non-stress conditions. Interacts (via N-terminus) with RASSF1 (via C-terminus); the interaction is independent of MDM2 and TP53; RASSF1 isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage. Interacts with ATRX to form the chromatin remodeling complex ATRX:DAXX. Interacts with HSF1 (via homotrimeric form preferentially); this interaction relieves homotrimeric HSF1 from repression of its transcriptional activity by HSP90-dependent multichaperone complex upon heat shock (By similarity).|||PML body|||Polyubiquitinated; which is promoted by CUL3 and SPOP and results in proteasomal degradation. Ubiquitinated by MDM2; inducing its degradation. Deubiquitinated by USP7; leading to stabilize it (By similarity).|||Repressor activity is down-regulated upon Ser-669 phosphorylation. Upon neuronal activation dephosphorylated by calcineurin in a Ca2+ dependent manner at Ser-669; dephosphorylation positively affects histone H3.3 loading and transcriptional activation.|||Sumoylated with SUMO1 on multiple lysine residues.|||The Sumo interaction motif mediates Sumo binding, and is required both for sumoylation and binding to sumoylated targets.|||Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as histone chaperone that facilitates deposition of histone H3.3. Acts as targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upon neuronal activation associates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (By similarity).|||centromere|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Cmss1 ^@ http://purl.uniprot.org/uniprot/Q9CZT6 ^@ Similarity ^@ Belongs to the CMS1 family. http://togogenome.org/gene/10090:Or5b95 ^@ http://purl.uniprot.org/uniprot/Q8VFW8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm13288 ^@ http://purl.uniprot.org/uniprot/Q8CD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Cpeb3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J102|||http://purl.uniprot.org/uniprot/D3Z1R6|||http://purl.uniprot.org/uniprot/Q7TN99 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by NEURL1-mediated monoubiquitination, resulting in the growth of new dendritic spines and increased levels of GRIA1 and GRIA2. NEURL1-mediated monoubiquitination facilitates synaptic plasticity and hippocampal-dependent memory storage.|||Belongs to the RRM CPEB family.|||Cytoplasm|||Enhanced thermal sensitivity and increased levels of Trpv1 in lumbar sciatic nerves and spinal cord (PubMed:26915043). Elevated short-term fear response, enhanced long-term spatial memory, dendritic spine enlargement and elevated levels of Dlg4/Psd95, Gria1 and NMDA receptor subunits Grin1, Grin2a and Grin2b (PubMed:26074071). Conditional knockout in the adult forebrain results in viable mice with no gross neurological defects which display normal locomotor, exploratory and anxiety behaviors but have impaired long-term memory, impaired long-term synaptic plasticity and increased levels of Gria1 and Gria2 (PubMed:26074003).|||Following neuronal stimulation, cleaved by CAPN2 which abolishes its translational repressor activity, leading to translation of CPEB3 target mRNAs.|||Following synaptic activity, aggregates to form amyloid-like oligomers (PubMed:26074003, PubMed:26074072). Aggregation requires an intact actin cytoskeleton (PubMed:26074072). Interacts with STAT5B; this inhibits STAT5B-mediated transcriptional activation (PubMed:20639532). Interacts with E3 ubiquitin-protein ligase NEURL1; this leads to monoubiquitination and activation of CPEB3 (PubMed:22153079). Interacts with CAPN2; this leads to cleavage of CPEB3 (PubMed:22711986). Interacts (via C-terminal RNA-binding region) with TOB1; TOB1 also binds CNOT7/CAF1 and recruits it to CPEB3 to form a ternary complex (By similarity). Interacts with SUMO-conjugating enzyme UBC9 (PubMed:26074071). Interacts with IPO5; the interaction is enhanced in a RAN-regulated manner following neuronal stimulation and mediates CPEB3 nuclear import (By similarity). Interacts with exportin XPO1/CRM1 (By similarity).|||Highly expressed in brain (at protein level) (PubMed:17024188). In brain, expressed in the hippocampus, granule cells and interneurons of the cerebellum, and mitral cells of the olfactory bulb (at protein level) (PubMed:17024188). Detected in the spinal cord and in peripheral dorsal root ganglia (at protein level) (PubMed:26915043). In the retina, strongly expressed in the retinal ganglion layer and, to a lesser extent, in the inner margin of the inner nuclear layer with expression also detected in the inner and outer plexiform layers (at protein level) (PubMed:20003455). Highly expressed in brain and heart, less in liver, kidney, embryo, skeletal muscle, lung and ovary (PubMed:12871996). Weakly expressed in granular cells of dentate gyrus and the pyramidal cells of CA3 and CA1 of the hippocampus (PubMed:12871996).|||In the retina, expression increases throughout postnatal development and remains high in the adult (at protein level).|||Nucleus|||Phosphorylation is enhanced by neuronal stimulation.|||Postsynaptic density|||Sequence-specific RNA-binding protein which acts as a translational repressor in the basal unstimulated state but, following neuronal stimulation, acts as a translational activator (PubMed:17024188, PubMed:26074072). In contrast to CPEB1, does not bind to the cytoplasmic polyadenylation element (CPE), a uridine-rich sequence element within the mRNA 3'-UTR, but binds to a U-rich loop within a stem-loop structure (PubMed:17024188). Required for the consolidation and maintenance of hippocampal-based long term memory (PubMed:26074003). In the basal state, binds to the mRNA 3'-UTR of the glutamate receptors GRIA1 and GRIA2 and negatively regulates their translation (PubMed:17024188, PubMed:22153079). Also represses the translation of DLG4, GRIN1 GRIN2A and GRIN2B (PubMed:24155305). When activated, acts as a translational activator of GRIA1 and GRIA2 (PubMed:22153079, PubMed:26074003). In the basal state, suppresses SUMO2 translation but activates it following neuronal stimulation (PubMed:26074071). Binds to the 3'-UTR of TRPV1 mRNA and represses TRPV1 translation which is required to maintain normal thermoception (PubMed:26915043). Binds actin mRNA, leading to actin translational repression in the basal state and to translational activation following neuronal stimulation (PubMed:26074072). Negatively regulates target mRNA levels by binding to TOB1 which recruits CNOT7/CAF1 to a ternary complex and this leads to target mRNA deadenylation and decay (By similarity). In addition to its role in translation, binds to and inhibits the transcriptional activation activity of STAT5B without affecting its dimerization or DNA-binding activity. This, in turn, represses transcription of the STAT5B target gene EGFR which has been shown to play a role in enhancing learning and memory performance (By similarity). In contrast to CPEB1, CPEB2 and CPEB4, not required for cell cycle progression (By similarity).|||Synapse|||The N-terminal Gln-rich region is required for the formation of amyloid-like oligomers and for the stability of long-term potentiation and spatial memory.|||Under basal unstimulated conditions when CPEB3 is mainly unaggregated, sumoylated and acts as a translational repressor. Following neuronal stimulation, becomes desumoylated and aggregated which is required for the translation of mRNA targets and for dendritic filopodia formation.|||Up-regulated following synaptic activity (at protein level) (PubMed:26074003, PubMed:26074072). Up-regulated in granular cells of the dentate gyrus and the pyramidal cells of CA1 and CA3 after kainate-induced seizures (PubMed:12871996).|||dendrite http://togogenome.org/gene/10090:Or7e170 ^@ http://purl.uniprot.org/uniprot/Q8VFJ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pla2g3 ^@ http://purl.uniprot.org/uniprot/Q6AXH0|||http://purl.uniprot.org/uniprot/Q8BZT7 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion.|||Cell membrane|||Expressed in dermal mast cells (at protein level) (PubMed:23624557). Highly expressed in EPCAM-positive colonic epithelial cells throughout the proximal to distal colon (at protein level) (PubMed:28947740). Expressed at lower levels in ileum section of small intestine and immune organs including bone marrow, spleen and lymph nodes (PubMed:28947740, PubMed:20424323). Expressed in stomach and lung (at protein level) (PubMed:17868035). Expressed in testis and epididymis and to a lesser extent in the seminal vesicles and prostate (PubMed:20424323). Detected in ovary, oviduct and uterus (PubMed:20424323). Expressed in Sertoli and Leydig cells as well as in epididymal epithelium particularly in apical border of principal cells in the corpus (at protein level) (PubMed:20424323). Present in cauda epididymal fluid (at protein level) (PubMed:20424323). Expressed in central nervous system, with high levels in spinal cord and at a lesser extent in brain (at protein level) (PubMed:17868035, PubMed:20424323).|||Highly expressed in dorsal root ganglia of the developing brain at 12.5 dpc (at protein level).|||In several cell types, the N- and C-termini are cleaved off.|||Male mutant mice have reduced fertility associated with reduced sperm cell motility, aberrant acrosomes and flagella resulting in poor morula development. The litter size after intercrossing heterozygous mutant male and female mice is significantly smaller when compared to wild-type mice. Nevertheless, mutant offspring are born at approximately Mendelian proportions, have normal survival, appearance and behavior (PubMed:20424323). Mutant mice are resistant to both passive systemic and active cutaneous anaphylaxis (PubMed:23624557). In models of colon carcinogenesis either induced by azoxymethane procarcinogen or upon activation of oncogenic Wnt/beta-catenin signal due to a mutation in the APC gene (model of human familial adenomatous polyposis), mutant mice are resistant to tumorigeneis showing markedly decreased total tumor burden in the colon. In a colitis model induced by toxic dextran sulfate sodium, mutant mice are protected from shortening of the colon length and mucosal inflammation and rapidly recover from epithelial injury (PubMed:28947740).|||N-glycosylation does not affect the catalytic activity, but is required for proper secretion. A nonglycosylated form is observed in several cell types.|||Recycling endosome|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids without apparent head group selectivity (PubMed:20424323). Contributes to phospholipid remodeling of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (By similarity). May act in an autocrine and paracrine manner (PubMed:23624557). Secreted by immature mast cells, acts on nearby fibroblasts upstream to PTDGS to synthesize prostaglandin D2 (PGD2), which in turn promotes mast cell maturation and degranulation via PTGDR (PubMed:23624557). Secreted by epididymal epithelium, acts on immature sperm cells within the duct, modulating the degree of unsaturation of the fatty acyl components of phosphatidylcholines required for acrosome assembly and sperm cell motility (PubMed:20424323). Facilitates the replacement of fatty acyl chains in phosphatidylcholines in sperm membranes from omega-6 and omega-9 to omega-3 polyunsaturated fatty acids (PUFAs) (PubMed:20424323). Coupled to lipoxygenase pathway, may process omega-6 PUFAs to generate oxygenated lipid mediators in the male reproductive tract (PubMed:20424323). At pericentrosomal preciliary compartment, negatively regulates ciliogenesis likely by regulating endocytotic recycling of ciliary membrane protein (By similarity). Coupled to cyclooxygenase pathway provides arachidonate to generate prostaglandin E2 (PGE2), a potent immunomodulatory lipid in inflammation and tumorigenesis (By similarity). At colonic epithelial barrier, preferentially hydrolyzes phospholipids having arachidonate and docosahexaenoate at sn-2 position, contributing to the generation of oxygenated metabolites involved in colonic stem cell homeostasis (PubMed:28947740). Releases C16:0 and C18:0 lysophosphatidylcholine subclasses from neuron plasma membranes and promotes neurite outgrowth and neuron survival (PubMed:17868035).|||The phospholipase A2-like domain represents the fully processed form after N- and C-termini are cleaved off. It is the secreted mature form found in biological fluids.|||centriole http://togogenome.org/gene/10090:Mrpl38 ^@ http://purl.uniprot.org/uniprot/Q8K2M0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphatidylethanolamine-binding protein family. Mitochondrion-specific ribosomal protein mL38 subfamily.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ttll5 ^@ http://purl.uniprot.org/uniprot/Q8CHB8 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arg-186 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Belongs to the tubulin--tyrosine ligase family.|||Cytoplasm|||Highly expressed in brain, kidney, liver, spleen and testis (PubMed:17499049). Expressed in heart, lung, muscle and trachea (PubMed:17499049).|||Interacts with the transcriptional coactivators NCOA1/SRC-1 and NCOA2/TIF2.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Polyglutamylase which modifies tubulin, generating polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin (PubMed:17499049). Preferentially mediates ATP-dependent initiation step of the polyglutamylation reaction over the elongation step (PubMed:17499049). Preferentially modifies the alpha-tubulin tail over a beta-tail (PubMed:17499049). Required for CCSAP localization to both polyglutamylated spindle and cilia microtubules (By similarity). Increases the effects of transcriptional coactivator NCOA2/TIF2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction (By similarity).|||The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Uqcc4 ^@ http://purl.uniprot.org/uniprot/Q6RUT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UQCC4 family.|||Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508). Forms a complex, named COMA, composed of UQCC1, UQCC2 and UQCC4; activates MT-CYB translation (PubMed:35977508). Forms a complex, named COMC, composed of UQCC1, UQCC2; UQCC3 and UQCC4; mediates MT-CYB hemylation and association with the first nuclear-encoded complex III subunit UQCRQ (PubMed:35977508). Complexes COMA and COMB are bound to the mitochondrion inner membrane by UQCC4 (PubMed:35977508).|||Mitochondrion inner membrane|||Required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III (CIII) or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative phosphorylation. http://togogenome.org/gene/10090:Serinc5 ^@ http://purl.uniprot.org/uniprot/Q8BHJ6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TDE1 family.|||Cell membrane|||Restriction factor required to restrict infectivity of gammaretroviruses: acts by inhibiting early step of viral infection and impairing the ability of the viral particle to translocate its content to the cytoplasm (By similarity). Enhances the incorporation of serine into phosphatidylserine and sphingolipids. May play a role in providing serine molecules for the formation of myelin glycosphingolipids in oligodendrocytes (By similarity). http://togogenome.org/gene/10090:Akr1c18 ^@ http://purl.uniprot.org/uniprot/Q3U538|||http://purl.uniprot.org/uniprot/Q8K023 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldo/keto reductase family.|||Catalyzes the conversion of progesterone into 20-alpha-dihydroprogesterone (20 alpha-OHP).|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Cab39l ^@ http://purl.uniprot.org/uniprot/Q9DB16 ^@ Function|||Similarity|||Subunit ^@ Belongs to the Mo25 family.|||Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1 (By similarity).|||Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity. http://togogenome.org/gene/10090:Pate2 ^@ http://purl.uniprot.org/uniprot/Q3UW31 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PATE family.|||Expressed in prostate, testis, brain and lung.|||Secreted http://togogenome.org/gene/10090:Fgf10 ^@ http://purl.uniprot.org/uniprot/O35565 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Expressed abundantly in embryos and the lung, and at much lower levels in brain and heart.|||Interacts with FGFR1 and FGFR2. Interacts with FGFBP1 (By similarity).|||Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. May play a role in wound healing.|||Secreted http://togogenome.org/gene/10090:Gls2 ^@ http://purl.uniprot.org/uniprot/Q571F8 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glutaminase family.|||Enzyme activity is not stimulated by phosphate. Phosphate increases kcat, but decreases substrate affinity, resulting in unchanged enzyme activity.|||Homotetramer, dimer of dimers (By similarity). Does not assemble into higher oligomers (PubMed:23935106). Interacts with the PDZ domain of the syntrophin SNTA1. Interacts with the PDZ domain of TAX1BP3 (By similarity).|||Mitochondrion|||Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation. http://togogenome.org/gene/10090:Klhl14 ^@ http://purl.uniprot.org/uniprot/Q69ZK5 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Expressed in the brain, primarily in neurons. In the cerebral cortex, mostly expressed in layers I and II (at protein level). Also observed in some neurons of the corpus striatum (at protein level). Expressed at high levels in the hippocampus, including in pyramidal cells of the CA1 and CA3 layers (at protein level). In the cerebellum, expression in Purkinje cells is higher than in granular cells (at protein level). Also detected in the medial septum, ventral pallidum, thalamus, hypothalamus, amygdala, inferior colliculi, locus caeruleus, peripyramidal nucleus, raphe nucleus, reticular formation, spinal trigeminal nucleus, and vestibular nuclei (at protein level). Low expression, if any, in glial cells (at protein level). Not observed in the corpus callosum.|||Interacts with TOR1A.|||cytosol http://togogenome.org/gene/10090:Lrrc52 ^@ http://purl.uniprot.org/uniprot/Q5M8M9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium (By similarity). KCNU1 channel auxiliary protein. May modulate KCNU1 gating properties, shifting KCNU1 gating to more negative potentials at a given pH.|||Cell membrane|||Interacts with KCNMA1 (By similarity). May interact with KCNU1; this interaction may be required for LRRC52 stability and may change the channel gating properties.|||N-glycosylated.|||Testis-specific (at protein level). At the mRNA level, also detected in kidney, ventricle, spinal cord and skeletal muscle, although at lower levels compared to testis. Expression in testis at the protein level requires the presence of KCNU1.|||The transmembrane domain is necessary for interaction with KCNMA1.|||Very low expression levels in testis before postnatal day 25 (P25). Levels strongly increase between P25 and P30, and then remain high from P30 through P150. http://togogenome.org/gene/10090:Ctnnd2 ^@ http://purl.uniprot.org/uniprot/E9QKH8|||http://purl.uniprot.org/uniprot/O35927 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the beta-catenin family.|||Binds to E-cadherin at a juxtamembrane site within the cytoplasmic domain. Binds to PSEN1. Interacts with PDZD2 (By similarity). Interacts (via the extreme C-terminus) with FRMPD2 (via the PDZ 2 domain) (By similarity). Interacts with ZBTB33. Interacts with ARHGEF28 (PubMed:17993462). Interacts with CDK5 (By similarity). Interacts with CTNNB1 (By similarity). Interacts with GSK3A and GSK3B (PubMed:20623542) (PubMed:19706605). Interacts with DNM2 (By similarity). Interacts with CCDC85B (By similarity).|||By retinoic acid.|||Expressed in neurons and glial cells. Isoform 2 was found to be the most predominant isoform in various brain regions. Expressed at neuromuscular junctions.|||Has a critical role in neuronal development, particularly in the formation and/or maintenance of dendritic spines and synapses (PubMed:17993462) (PubMed:25807484). Involved in the regulation of canonical Wnt signaling (By similarity). It probably acts on beta-catenin turnover, facilitating beta-catenin interaction with GSK3B, phosphorylation, ubiquitination and degradation (PubMed:20623542). May be involved in neuronal cell adhesion and tissue morphogenesis and integrity by regulating adhesion molecules. Functions as a transcriptional activator when bound to ZBTB33 (PubMed:15282317).|||Increasingly expressed by 10 dpc. Expression peaks at postnatal day P7 and stays at lower levels in adulthood. First expressed within proliferating neuronal progenitor cells of the neuroepithelium, becomes down-regulated during neuronal migration, and is later reexpressed in the dendritic compartment of postmitotic neurons. In the developing neocortex, it is strongly expressed in the proliferative ventricular zone and the developing cortical plate, yet is conspicuously less prominent in the intermediate zone, which contains migrating cortical neurons, it forms a honeycomb pattern in the neuroepithelium by labeling the cell periphery in a typical adherens junction pattern. By 18 dpc, its expression shifts primarily to nascent apical dendrites, a pattern that continues through adulthood.|||Nucleus|||O-glycosylated.|||Perikaryon|||Phosphorylated by CDK5 (By similarity). Phosphorylated by GSK3B (PubMed:19706605).|||adherens junction|||dendrite http://togogenome.org/gene/10090:Grik2 ^@ http://purl.uniprot.org/uniprot/A0A1W2P6S5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. http://togogenome.org/gene/10090:Gsta2 ^@ http://purl.uniprot.org/uniprot/P10648 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Alpha family.|||Catalyzes the conjugation of glutathione to a large variety of electrophilic compounds.|||Expressed in the kidney.|||Homodimer (PubMed:12549910). Heterodimer of GSTA1 and GSTA2 (By similarity). http://togogenome.org/gene/10090:Lrp10 ^@ http://purl.uniprot.org/uniprot/Q7TQH7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LDLR family.|||Highly expressed in heart, lung, liver and liver. Expressed at low level in brain and spleen. Weakly or not expressed in testis and skeletal muscle. In liver, it is expressed in hepatocytes and at higher level in sinusoidal lining. In the kidney, it is expressed in peritubular capillaries. In brain, it is expressed in the epithelium of the choroid plexus ependymal cells of the third ventricle pia matter, and to lesser extent in hippocampal fields CA2 and CA3.|||Membrane|||Probable receptor, which is involved in the internalization of lipophilic molecules and/or signal transduction. May be involved in the uptake of lipoprotein APOE in liver.|||coated pit http://togogenome.org/gene/10090:Rgn ^@ http://purl.uniprot.org/uniprot/Q64374 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMP-30/CGR1 family.|||Binds 1 divalent metal cation per subunit. Most active with Zn(2+) and Mn(2+) ions. The physiological cofactor is most likely Ca(2+) or Mg(2+).|||By calcium.|||Cytoplasm|||Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Catalyzes a key step in ascorbic acid (vitamin C) biosynthesis. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent cellular processes and enzyme activities (By similarity).|||Mainly present in the liver. Weak expression was found in the brain, lung and kidney.|||Mice do not thrive after weaning when kept on a vitamin C-less diet. They develop scurvy, have reduced bone mineral density and brittle bones. Hepatocytes exhibit accumulation of lipid droplets. Mice display increased mortality after about 3 months, and their life span is shorter than normal.|||Monomer.|||Protein amounts in liver decrease significantly with age. http://togogenome.org/gene/10090:Iqcg ^@ http://purl.uniprot.org/uniprot/Q80W32 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DRC9 family.|||Component of the nexin-dynein regulatory complex (N-DRC) (By similarity). Interacts (via IQ domain) with CALM when calcium levels are low. Does not interact with CALM in the presence of Ca(2+) (PubMed:24849454). Interacts with the HSP70 proteins HSPA1L and HSPA8 (By similarity). May form a complex with CAMK4 and HSP70 (Probable).|||Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Binds calmodulin when cellular Ca(2+) levels are low and thereby contributes to the regulation of calcium and calmodulin-dependent protein kinase IV (CAMK4) activity; contributes to the regulation of CAMK4 signaling cascades (By similarity). Required for normal axoneme assembly in sperm flagella, normal sperm tail formation and for male fertility (PubMed:24362311, PubMed:24849454).|||Cytoplasm|||Early spermiogenesis defective 12d (esgd12d) is caused by mutations disrupting this gene. Affected male mice display complete loss of fertility; their sperm cells lack tails and are nonmotile.|||Expressed in the testes (at protein level) (PubMed:24362311, PubMed:24849454, PubMed:35547804). Also detected in oviduct (at protein level) (PubMed:24849454). Also detected in the trachea (PubMed:24849454).|||First detected in testis 17 days after birth when pachytene spermatocytes are seen in testes. Expression remains high during the first three weeks after birth and in adults (at protein level).|||No obvious phenotype, except complete male sterility (PubMed:24362311, PubMed:24849454). Female fertility is not altered (PubMed:24849454).|||The IQ domain mediates interaction with calmodulin when cellular Ca(2+) levels are low.|||cilium|||cytoskeleton|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Epop ^@ http://purl.uniprot.org/uniprot/Q7TNS8 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:21732481, PubMed:27462409, PubMed:27863225, PubMed:27863226). Within the complex, interacts with SUZ12 (via C2H2 zinc finger domain); competes with JARID2 for SUZ12 binding (By similarity). Associates with the elongin BC complex (PubMed:27863225, PubMed:27863226). Interacts with USP7 (PubMed:27863226).|||Chromosome|||Highly expressed in embryonic stem cells (ESCs) during embryogenesis and in the adult brain (PubMed:23180766).|||Highly expressed in embryonic stem cells (ESCs) during embryogenesis: expression starts from 4-cell stage.|||Nucleus|||Scaffold protein that serves as a bridging partner between the PRC2/EZH2 complex and the elongin BC complex: required to fine-tune the transcriptional status of Polycomb group (PcG) target genes in embryonic stem cells (ESCs) (PubMed:27863225, PubMed:27863226). Plays a key role in genomic regions that display both active and repressive chromatin properties in pluripotent stem cells by sustaining low level expression at PcG target genes: acts by recruiting the elongin BC complex, thereby restricting excessive activity of the PRC2/EZH2 complex (PubMed:27863225, PubMed:27863226). Interaction with USP7 promotes deubiquitination of H2B at promoter sites (PubMed:27863226). Acts as a regulator of neuronal differentiation (PubMed:23180766).|||The BC-box, which mediates binding to the elongin BC complex. http://togogenome.org/gene/10090:Or1l8 ^@ http://purl.uniprot.org/uniprot/Q8VFP6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gga1 ^@ http://purl.uniprot.org/uniprot/Q8R0H9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GGA protein family.|||Early endosome membrane|||Endosome membrane|||Monomer. Interacts with GGA2 and GGA3 (By similarity). Binds to clathrin and activated ARFs, including ARF1, ARF5 and ARF6 (PubMed:22522702, PubMed:11950392). Interacts with RABEP1 and RABGEF1 (PubMed:25405894). Interacts with the type-I membrane proteins LRP3, M6PR/CD-MPR and IGF2R/CI-MPR. Interacts (via N-terminal VHS domain) with SORL1/sorLA and SORT1 (via C-terminal cytosolic domain) (By similarity). Interacts with EPN4. Interacts with CCDC91 (By similarity). Interacts with HEATR5B/p200a (By similarity). Interacts with SYNRG/gamma-synergin (By similarity). Interacts (via GAE doamin) with NECAP1 and NECAP2 (By similarity). Interacts (via GAE domain) with AFTPH/aftiphilin (By similarity). Interacts with TSG101 and UBC. Interacts with RNF11. Interacts (via VHS domain) with BACE1 (via DXXLL motif); the interaction highly increases when BACE1 is phosphorylated at 'Ser-498' (By similarity). Interacts with CNST (PubMed:19864490). Interacts with ADRA2B (By similarity). Interacts with ARL3; the interaction recruits, in collaboration with RABEP1, PKD1:PKD2 complex to trans-Golgi network and is required for ciliary targeting (PubMed:25405894).|||Phosphorylated by CK2 and dephosphorylated by PP2A. Phosphorylation of GGA1 allows the internal DXXLL motif to bind the VHS domain and to inhibit the recognition of cargo signals.|||Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes (PubMed:25405894). Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell surface (By similarity). Required for targeting PKD1:PKD2 complex from the trans-Golgi network to the cilium membrane (PubMed:25405894). Regulates retrograde transport of proteins such as phosphorylated form of BACE1 from endosomes to the trans-Golgi network (By similarity).|||The GAE domain binds accessory proteins regulating GGAs function.|||The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis.|||The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif).|||The unstructured hinge region contains clathrin-binding but no autoinhibitory (DXXLL) motifs.|||Ubiquitinated.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Plcd4 ^@ http://purl.uniprot.org/uniprot/Q8K3R3 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.|||By treatment with growth factors such as bradykinin, lysophosphatidic acid, and Ca(2+) ionophore in addition to serum.|||Cytoplasm|||Endoplasmic reticulum|||Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca(2+) mobilization in the zona pellucida-induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation.|||Interacts with GRIP1 (PubMed:16272139). Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (inactive GDP-bound form)l low-affinity interaction (By similarity).|||Membrane|||Mice are either sterile or produce few small litters. In these mice, fewer eggs become activated and the Ca(2+) transients associated with fertilization are absent or delayed. Sperm are unable to initiate the acrosome reaction.|||Nucleus|||The C2 domain mediates pre-localization to the membrane prior to Ca(2+) import and non-selective Ca(2+)-mediated targeting to various cellular membranes.|||The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).|||The PDZ-binding motif mediates the interaction with GRIP1.|||The PH domain is not a critical determinant of the membrane localization. http://togogenome.org/gene/10090:Stx16 ^@ http://purl.uniprot.org/uniprot/Q0VGN4|||http://purl.uniprot.org/uniprot/Q8BVI5|||http://purl.uniprot.org/uniprot/Q8C0W8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Golgi apparatus membrane|||Interacts with GCC2 (By similarity). Interacts with BAIAP3; this interaction is increased in the presence of calcium (By similarity).|||SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network. http://togogenome.org/gene/10090:Hmox1 ^@ http://purl.uniprot.org/uniprot/P14901|||http://purl.uniprot.org/uniprot/Q3U5U6 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A soluble form arises by proteolytic removal of the membrane anchor.|||Belongs to the heme oxygenase family.|||Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron (By similarity) Affords protection against programmed cell death and this cytoprotective effect relies on its ability to catabolize free heme and prevent it from sensitizing cells to undergo apoptosis (By similarity).|||Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.|||Endoplasmic reticulum membrane|||Homodimer and higher order homooligomer. Oligomerization is crucial for its stability and function in the endoplasmic reticulum (By similarity). Interacts with FLVCR2; this interaction is potentiated in the presence of heme.|||Induced by its substrate heme, CdCl2, sodium arsenite and 12-O-tetradecanoyl-phorbol-13-acetate (PubMed:3409220, PubMed:8288554). It is also induced in macrophages, liver and the lungs upon infection with M.tuberculosis (at protein level). Data is conflicting as to whether macrophage induction is independent of the nitric oxide (NO) signaling pathway (PubMed:18400743), or dependent on NO (PubMed:18474359).|||The transmembrane domain is necessary for its oligomerization. http://togogenome.org/gene/10090:Ces1g ^@ http://purl.uniprot.org/uniprot/Q3UW56|||http://purl.uniprot.org/uniprot/Q8VCC2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Cytoplasm|||Detected in kidney, liver and lung.|||Endoplasmic reticulum lumen|||Homotrimer and homohexamer. Binds to beta-glucuronidase (By similarity).|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate. Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins. Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process. First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile.|||Lipid droplet|||Up-regulated in liver upon feeding a diet enriched in cholestyramine or cholate. http://togogenome.org/gene/10090:Tgm5 ^@ http://purl.uniprot.org/uniprot/Q9D7I9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 1 Ca(2+) ion per subunit.|||Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Contributes to the formation of the cornified cell envelope of keratinocytes (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Or2ag15 ^@ http://purl.uniprot.org/uniprot/Q8VFM4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Myl2 ^@ http://purl.uniprot.org/uniprot/P51667 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A band|||Abundantly expressed in both cardiac and slow skeletal muscle (PubMed:1379240). In the adult heart, the phosphorylated form is highly expressed in epicardium and weakly in endocardium (PubMed:22426213).|||At 8 dpc highly expressed in the ventricular portion of the heart tube, with no detectable expression in the atrial or sinus venosus regions; also expressed in the proximal outflow tract of the heart tube at minimally detectable levels. At 9-10 dpc expression is well established in the proximal outflow tract region adjacent to the ventricular segment. At 11 dpc, expression becomes restricted to the ventricular region.|||Contractile protein that plays a role in heart development and function (PubMed:10409661). Following phosphorylation, plays a role in cross-bridge cycling kinetics and cardiac muscle contraction by increasing myosin lever arm stiffness and promoting myosin head diffusion; as a consequence of the increase in maximum contraction force and calcium sensitivity of contraction force. These events altogether slow down myosin kinetics and prolong duty cycle resulting in accumulated myosins being cooperatively recruited to actin binding sites to sustain thin filament activation as a means to fine-tune myofilament calcium sensitivity to force (By similarity) (PubMed:22426213, PubMed:16908724, PubMed:10409661). During cardiogenesis plays an early role in cardiac contractility by promoting cardiac myofibril assembly (PubMed:9422794).|||Myl2 homozygous die at 12.5 dpc, which is associated with ultrastructural defects in ventricular sarcomere assembly, that included disruptions and disorganization of the normal parallel alignment of the thick and thin filaments, narrower fiber widths and larger distances between Z disks and misalignment of Z-band between sarcomeres.|||Myosin is a hexamer of 2 heavy chains and 4 light chains (By similarity). Interacts with MYOC (By similarity).|||N-terminus is methylated by METTL11A/NTM1.|||Phosphorylated by MYLK3 and MYLK2; promotes cardiac muscle contraction and function. Dephosphorylated by PPP1CB complexed to PPP1R12B (By similarity). The phosphorylated form in adult is expressed as gradients across the heart from endocardium (low phosphorylation) to epicardium (high phosphorylation); regulates cardiac torsion and workload distribution (PubMed:22426213).|||This chain binds calcium. http://togogenome.org/gene/10090:Rps3 ^@ http://purl.uniprot.org/uniprot/P62908|||http://purl.uniprot.org/uniprot/Q5YLW3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS3 family.|||Component of the 40S small ribosomal subunit (PubMed:36517592). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with HNRPD. Interacts with PRMT1; the interaction methylates RPS3. Interacts with SUMO1; the interaction sumoylates RPS3. Interacts with UBC9. Interacts with CDK1; the interaction phosphorylates RPS3. Interacts with PRKCD; the interaction phosphorylates RPS3. Interacts with PKB/AKT; the interaction phosphorylates RPS3. Interacts with E2F1; the interaction occurs in the absence of nerve growth factor and increases transcription of pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5. Interacts with the base excision repair proteins APEX1 and OGG1; interaction with OGG1 increases OGG1 N-glycosylase activity. Interacts with UNG; the interaction increases the uracil excision activity of UNG1. Interacts with HSP90; the interaction prevents the ubiquitination and proteasome-dependent degradation of RPS3 and is suppressed by increased ROS levels. Interacts with TOM70; the interaction promotes translocation of RPS3 to the mitochondrion. Interacts (via N-terminus) with RELA (via N-terminus); the interaction enhances the DNA-binding activity of the NF-kappa-B p65-p50 complex. Interacts with NFKBIA; the interaction is direct and may bridge the interaction between RPS3 and RELA. Interacts with IKKB; the interaction phosphorylates RPS3 and enhances its translocation to the nucleus. Interacts (via KH domain) with MDM2 and TP53. Interacts with TRADD. Interacts with CRY1.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (By similarity). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (By similarity). Has also been shown to bind with similar affinity to intact and damaged DNA (By similarity). Stimulates the N-glycosylase activity of the base excision protein OGG1 (By similarity). Enhances the uracil excision activity of UNG1 (By similarity). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (By similarity). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (By similarity). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (By similarity). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (By similarity). Represses its own translation by binding to its cognate mRNA (By similarity). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (By similarity). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (By similarity). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (By similarity). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (By similarity).|||Cytoplasm|||Membrane|||Methylation by PRMT1 is required for import into the nucleolus and for ribosome assembly.|||Mitochondrion inner membrane|||Nucleus|||Phosphorylation at Thr-221 by CDK1 occurs mainly in G2/M phase. Phosphorylation by PRKCD occurs on a non-ribosomal-associated form which results in translocation of RPS3 to the nucleus and enhances its endonuclease activity. Phosphorylated on Ser-209 by IKKB in response to activation of the NF-kappa-B p65-p50 complex which enhances the association of RPS3 with importin-alpha and mediates the nuclear translocation of RPS3. Phosphorylation by MAPK is required for translocation to the nucleus following exposure of cells to DNA damaging agents such as hydrogen peroxide. Phosphorylation by PKB/AKT mediates RPS3 nuclear translocation, enhances RPS3 endonuclease activity and suppresses RPS3-induced neuronal apoptosis.|||Sumoylation by SUMO1 enhances protein stability through increased resistance to proteolysis. Sumoylation occurs at one or more of the three consensus sites, Lys-18, Lys-214 and Lys-230.|||Ubiquitinated; ubiquitination is prevented by interaction with HSP90 which stabilizes the protein. Monoubiquitinated at Lys-214 by RNF10 and ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide. Deubiquitinated at Lys-214 by USP10, preventing degradation by the proteasome and promoting 40S ribosome subunit recycling following ribosome dissociation.|||Ufmylated by UFL1.|||nucleolus|||spindle http://togogenome.org/gene/10090:Rabac1 ^@ http://purl.uniprot.org/uniprot/Q9Z0S9 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRA1 family.|||Cell membrane|||Cytoplasm|||General Rab protein regulator required for vesicle formation from the Golgi complex. May control vesicle docking and fusion by mediating the action of Rab GTPases to the SNARE complexes. In addition it inhibits the removal of Rab GTPases from the membrane by GDI1 (By similarity).|||Golgi apparatus|||Homodimer. Interacts with VAMP2 (synaptobrevin-2), GDI1, NRDG1 and PCLO (By similarity). Interacts with prenylated Rab proteins (including RAB5 and RAB6), and with the members of the Ras superfamily HRAS, RHOA, TC21, and RAP1A.|||Interaction with the Ras-like GTPases failed to be confirmed in other species.|||synaptic vesicle http://togogenome.org/gene/10090:Rhbdl3 ^@ http://purl.uniprot.org/uniprot/P58873 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ At 8 dpc, expression is limited to the developing central nervous system (CNS). From 9 dpc on detected in the ventral forebrain, pretectum, dorsal diencephalon, metencephalon, the ventral spinal neural tube, in the ectoderm of the developing mandibular arches and the developing hindgut.|||Belongs to the peptidase S54 family.|||May be involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors.|||Membrane http://togogenome.org/gene/10090:Spink11 ^@ http://purl.uniprot.org/uniprot/Q09TK7 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in epydiymis, in the caput. Also expressed in seminal vesicles.|||Probable serine protease inhibitor.|||Secreted http://togogenome.org/gene/10090:Arhgef3 ^@ http://purl.uniprot.org/uniprot/A0A286YDE6|||http://purl.uniprot.org/uniprot/A0A2X0SFN9|||http://purl.uniprot.org/uniprot/Q91X46 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.|||Cytoplasm|||Interacts with RHOA and RHOB. http://togogenome.org/gene/10090:S100pbp ^@ http://purl.uniprot.org/uniprot/Q9D5K4 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts with S100P.|||Nucleus http://togogenome.org/gene/10090:Wnt10a ^@ http://purl.uniprot.org/uniprot/P70701 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Wnt family.|||Detected in foot plant epidermis, footpad epidermis, haired skin epidermis. Detected in adult epithelia, including filiform and fungiform papillae and sweat ducts. Detected in sweat gland myoepithelial cells, but not in sweat gland mesenchyme.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids.|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway. Plays a role in normal ectoderm development. Required for normal tooth development. Required for normal postnatal development and maintenance of tongue papillae and sweat ducts. Required for normal proliferation of basal cells in tongue filiform papillae, plantar epithelium and sweat ducts. Required for normal expression of keratins in tongue papillae. Required for normal expression of KRT9 in foot plant epithelium. Required for normal hair follicle function.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Gpr50 ^@ http://purl.uniprot.org/uniprot/O88495 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Does not bind melatonin.|||Homodimer, and heterodimer with MTNR1A and MTNR1B.|||It is uncertain whether Met-1 or Met-9 is the initiator. http://togogenome.org/gene/10090:Ppp1r14c ^@ http://purl.uniprot.org/uniprot/Q8R4S0 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PP1 inhibitor family.|||Detected in heart, muscle, spinal cord, hippocampus, hypothalamus, thalamus, midbrain, brain stem, cerebellum, brain cortex and olfactory bulb.|||Endomembrane system|||Inhibitor of the PP1 regulatory subunit PPP1CA.|||The main inhibitory site appears to be Thr-72 (By similarity). Has over 600-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction.|||Up-regulated by morphine. http://togogenome.org/gene/10090:Tex15 ^@ http://purl.uniprot.org/uniprot/F8VPN2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TEX15 family.|||Cytoplasm|||Detected in testis and ovary, and at lower levels in lung and brain.|||Highly expressed in embryonic male germ cells at embryonic days 16.5 dpc and 18.5 dpc and expression increases at postnatal day 2.5.|||Interacts with PIWIL4 (PubMed:32719317). Interacts with PIWIL2 (PubMed:32381626).|||Nucleus|||Required during spermatogenesis for normal chromosome synapsis and meiotic recombination in germ cells. Necessary for formation of DMC1 and RAD51 foci on meiotic chromosomes, suggesting a specific role in DNA double-stranded break repair (PubMed:18283110). Essential executor of PIWIL4-piRNA pathway directed transposon DNA methylation and silencing in the male embryonic germ cells (PubMed:32381626, PubMed:32719317). PIWIL4-piRNA binds to nascent transposon transcripts and interacts with TEX15, which may in turn recruit the epigenetic silencing machinery to the transposon loci (PubMed:32381626). Not required for piRNA biosynthesis (PubMed:32381626, PubMed:32719317).|||Viable with no gross phenotype. Male mice are infertile with significantly reduced testis size, while females are fertile. Severe depletion of germ cells in seminiferous tubules and epididymal tubules, due to meiotic arrest (PubMed:18283110, PubMed:32381626, PubMed:32719317). Male germ cells show derepression of transposable elements (TEs) and severe DNA hypomethylation of TEs (PubMed:32381626, PubMed:32719317). http://togogenome.org/gene/10090:Cadm1 ^@ http://purl.uniprot.org/uniprot/E9PYN1|||http://purl.uniprot.org/uniprot/Q8R5M8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nectin family.|||Cell membrane|||Expressed dominantly in epithelial cells but not expressed in fibroblast cells (at protein level) (PubMed:12826663). Expressed in the T-cell area of lymph nodes, specifically in CD8+ and CD4- CD8- dendritic cells (at protein level) (PubMed:19752223). Expressed in CD8+ dendritic cells in the spleen (at protein level) (PubMed:19752223). Expressed in CD103+ dendritic cells in the small intestine lamina propria and mesenteric lymph nodes (at protein level) (PubMed:24687959). Expressed in brain, lung, kidney, testis, heart, spleen and liver, but not expressed in skeletal muscle (PubMed:12242005, PubMed:12606335, PubMed:12202822).|||Expressed in spermatogenic cells during early spermatogenesis. Expression increases in intermediate spermatogonia through to zygotene spermatocytes but becomes diminished in the steps from early pachytene spermatocytes through to round spermatids. After meiosis, expression reappears in spermatids and is present in elongating spermatids until spermiation. Not detected in Sertoli cells.|||Glycosylation at Asn-70 and Asn-104 promotes adhesive binding and synapse induction.|||Homodimer (via Ig-like V-type domain) (By similarity). Interacts with FARP1 (PubMed:23209303). Interacts (via Ig-like V-type domain) with CRTAM (via Ig-like V-type domain); the interaction competes with CRTAM homodimerization and CADM1 homodimerization (PubMed:15811952, PubMed:15781451). Interacts (via C-terminus) with EPB41L3/DAL1 (By similarity). The interaction with EPB41L3/DAL1 may act to anchor CADM1 to the actin cytoskeleton (By similarity). Interacts (via C-terminus) with MPP2 (via PDZ domain) (By similarity). Interacts (via C-terminus) with MPP3 (via PDZ domain); this interaction connects CADM1 with DLG1 (By similarity). Interacts (via C-terminus) with PALS2 (via PDZ domain) (PubMed:12826663).|||Male mice are infertile, due to a defect at the spermatid stage of spermatogenesis, and show oligoasthenoteratozoospermia with almost no mature motile spermatozoa in the epididymis (PubMed:16382161, PubMed:16611999, PubMed:16612000). Heterozygous males and females and homozygous null females are fertile and have no overt developmental defects (PubMed:16382161, PubMed:16611999, PubMed:16612000). In the small intestine mucosa and under steady-state conditions, severe reduction in the number of intraepithelial CD4+ CD8+ T-cells and, partial reduction in the number of lamina propria and intraepithelial CD8+ and CD4+ T-cells (PubMed:24687959).|||Mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner (PubMed:12202822, PubMed:12799182, PubMed:12826663). Also mediates heterophilic cell-cell adhesion with CADM3 and NECTIN3 in a Ca(2+)-independent manner (PubMed:12826663). Interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ T-cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM1 in vivo (PubMed:15811952). In mast cells, may mediate attachment to and promote communication with nerves (By similarity). CADM1, together with MITF, is essential for development and survival of mast cells in vivo (PubMed:15158462, PubMed:16605125). By interacting with CRTAM and thus promoting the adhesion between CD8+ T-cells and CD8+ dendritic cells, regulates the retention of activated CD8+ T-cell within the draining lymph node (PubMed:19752223). Required for the intestinal retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent, intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells (PubMed:24687959). Interaction with CRTAM promotes the adhesion to gut-associated CD103+ dendritic cells, which may facilitate the expression of gut-homing and adhesion molecules on T-cells and the conversion of CD4+ T-cells into CD4+ CD8+ T-cells (PubMed:24687959). Acts as a synaptic cell adhesion molecule and plays a role in the formation of dendritic spines and in synapse assembly (PubMed:12202822, PubMed:23209303). May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons (PubMed:15707673). May play diverse roles in the spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa (PubMed:12606335, PubMed:16612000).|||N-glycosylated.|||Synaptic cell membrane|||The cytoplasmic domain appears to play a critical role in proapoptosis and tumor suppressor activity in NSCLC. http://togogenome.org/gene/10090:Nat8l ^@ http://purl.uniprot.org/uniprot/Q3UGX3 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 'Shati' is the name of the symbol at Nagoya castle in Japan.|||Aminooxyacetic acid (AOAA) blocks its activity in both cytoplasm and mitochondria.|||Belongs to the camello family.|||By methamphetamine in brain, via dopamine receptor activation (at protein level).|||Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA (PubMed:19807691, PubMed:20385109, PubMed:20643647). Promotes dopamine uptake by regulating TNF-alpha expression (PubMed:19014384). Attenuates methamphetamine-induced inhibition of dopamine uptake (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in brain, kidney, liver and spleen. In brain, present in neurons but not in astrocytes (at protein level). Expressed in brain, thymus and spleen.|||Microsome membrane|||Mitochondrion membrane|||Seems to modulate behavioral effects induced by methamphetamine in vivo. http://togogenome.org/gene/10090:Or8d1b ^@ http://purl.uniprot.org/uniprot/Q9EQA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chmp4c ^@ http://purl.uniprot.org/uniprot/Q9D7F7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||Late endosome membrane|||Midbody ring|||Phosphorylated at Ser-210 by AURKB during cytokinesis: together with ZFYVE19/ANCHR, phosphorylated CHMP4C retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis.|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: upon phosphorylation by AURKB, together with ZFYVE19/ANCHR, retains abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ANCHR and VPS4 and subsequent abscission. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Self-associates. Interacts with CHMP2A. Interacts with CHMP4A. Interacts with CHMP4B. Interacts with CHMP6. Interacts with VPS4A. Interacts with PDCD6IP; the interaction is direct (By similarity).|||The acidic C-terminus and the basic N-terminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components (By similarity).|||cytosol http://togogenome.org/gene/10090:Rsc1a1 ^@ http://purl.uniprot.org/uniprot/Q9ER99 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in epithelial and subepithelial cells of small intestine.|||Interacts with YRDC.|||Mediates transcriptional and post-transcriptional regulation of SLC5A1. Inhibits a dynamin and PKC-dependent exocytotic pathway of SLC5A1. Also involved in transcriptional regulation of SLC22A2. Exhibits glucose-dependent, short-term inhibition of SLC5A1 and SLC22A2 by inhibiting the release of vesicles from the trans-Golgi network (By similarity). Regulates the expression of SLC5A1 in a tissue-specific manner and is specifically involved in its regulation in the small intestine.|||Mice show a specific phenotype: first, a post-transcriptional up-regulation of SLC5A1 in the small intestine, with an increased d-glucose absorption rate and capacity; second, an increased food intake that results in a visceral type of obesity.|||Nucleus|||trans-Golgi network http://togogenome.org/gene/10090:Tmed1 ^@ http://purl.uniprot.org/uniprot/B2RRM5|||http://purl.uniprot.org/uniprot/Q3V009 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EMP24/GP25L family.|||Cell membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Homodimer in endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and cis-Golgi network. Interacts with IL1RL1. Interacts with RNF26; this interaction is important to modulate innate immune signaling through the cGAS-STING pathway.|||Membrane|||Potential role in vesicular protein trafficking, mainly in the early secretory pathway. May act as a cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and may be involved in vesicle coat formation at the cytoplasmic side. Plays a positive role in IL-33-mediated IL-8 and IL-6 production by interacting with interleukin-33 receptor IL1RL1. Plays also a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26.|||Widely expressed.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Thap4 ^@ http://purl.uniprot.org/uniprot/Q6P3Z3 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Binds 1 heme b group per subunit, that coordinates a highly solvent-exposed Fe(III) atom.|||Cytoplasm|||Heme-binding protein able to scavenge peroxynitrite and to protect free L-tyrosine against peroxynitrite-mediated nitration, by acting as a peroxynitrite isomerase that converts peroxynitrite to nitrate. Therefore, this protein likely plays a role in peroxynitrite sensing and in the detoxification of reactive nitrogen and oxygen species (RNS and ROS, respectively). Is able to bind nitric oxide (NO) in vitro, but may act as a sensor of peroxynitrite levels in vivo, possibly modulating the transcriptional activity residing in the N-terminal region.|||Homodimer.|||In the C-terminal section; belongs to the nitrobindin family.|||Nucleus|||The C-terminal nitrobindin region coordinates a heme and bears the isomerase activity. The N-terminal zinc finger domain likely binds DNA and may be involved in transcriptional regulation. http://togogenome.org/gene/10090:Ffar2 ^@ http://purl.uniprot.org/uniprot/Q8VCK6 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||During differentiation of leukocytes. This induction is STAT3-dependent. Up-regulated in adipose tissues by high-fat diet.|||G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins but also to the Gq family (PubMed:23589301). Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. May play a role in glucose homeostasis by regulating the secretion of GLP-1, in response to short-chain fatty acids accumulating in the intestine (PubMed:22190648, PubMed:23589301). May also regulate the production of LEP/Leptin, a hormone acting on the central nervous system to inhibit food intake (PubMed:20399779). Finally, may also regulate whole-body energy homeostasis through adipogenesis regulating both differentiation and lipid storage of adipocytes (PubMed:16123168, PubMed:23589301). In parallel to its role in energy homeostasis, may also mediate the activation of the inflammatory and immune responses by SCFA in the intestine, regulating the rapid production of chemokines and cytokines (PubMed:23665276). May also play a role in the resolution of the inflammatory response and control chemotaxis in neutrophils (PubMed:19917676, PubMed:19865172). In addition to SCFAs, may also be activated by the extracellular lectin FCN1 in a process leading to activation of monocytes and inducing the secretion of interleukin-8/IL-8 in response to the presence of microbes.|||Highly expressed in hematopoietic tissues, such as spleen and bone marrow, with highest levels in a subset of immune cells, including monocytes or neutrophils. Expressed in adipose tissues with high expression in differentiating adipocytes. Expressed by intestinal endocrine cells.|||Interacts with FCN1 (via Fibrinogen C-terminal domain).|||Knockout mice display altered protective intestinal inflammatory and immune responses but no gross developmental defects. http://togogenome.org/gene/10090:Slc6a14 ^@ http://purl.uniprot.org/uniprot/A1L359|||http://purl.uniprot.org/uniprot/Q9JMA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Amino acid transporter that plays an important role in the absorption of amino acids in the intestinal tract. Mediates the uptake of a broad range of neutral and cationic amino acids (with the exception of proline) in a Na(+)/Cl(-)-dependent manner (PubMed:11306607, PubMed:11447016). Transports non-alpha-amino acids such as beta-alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine (By similarity). Can also transport carnitine, butyrylcarnitine and propionylcarnitine coupled to the transmembrane gradients of Na(+) and Cl(-) (PubMed:11306651).|||Apical cell membrane|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A14 subfamily.|||Expressed in the distal region of the intestinal tract: cecum and colon.|||Membrane http://togogenome.org/gene/10090:Or11h6 ^@ http://purl.uniprot.org/uniprot/Q7TRL9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gtf3c6 ^@ http://purl.uniprot.org/uniprot/Q9D8P7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIIC subunit 6 family.|||Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters (By similarity).|||Nucleus|||Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with GTF3C4 and GTF3C5 (By similarity). http://togogenome.org/gene/10090:Acp1 ^@ http://purl.uniprot.org/uniprot/Q4VAI2|||http://purl.uniprot.org/uniprot/Q561M1|||http://purl.uniprot.org/uniprot/Q9D358 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates with differences in substrate specificity between isoform 1 and isoform 2.|||Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.|||Belongs to the low molecular weight phosphotyrosine protein phosphatase family.|||Cytoplasm|||Inhibited by sulfhydryl reagents.|||Interacts with EPHA2; dephosphorylates EPHA2. Interacts with EPHB1.|||Interacts with the SH3 domain of SPTAN1. There is no interaction observed for isoform 2.|||Phosphorylated by LCK. Phosphorylation at Tyr-132 increases its phosphatase activity.|||Widely expressed with highest levels in brain and liver and lowest levels in muscle. http://togogenome.org/gene/10090:Vegfd ^@ http://purl.uniprot.org/uniprot/P97946 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDGF/VEGF growth factor family.|||By the transcription factor c-fos.|||Expressed in a dynamic pattern in several body structures and organs of the embryo such as limb buds, acoustic ganglion, teeth, heart, anterior pituitary as well as lung and kidney mesenchyme, liver, derma, and periosteum of the vertebral column.|||Growth factor active in angiogenesis, lymphangiogenesis and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in the formation of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates VEGFR-3 (Flt4) receptor.|||Highly expressed in fetal and adult lung.|||Homodimer; non-covalent and antiparallel.|||Secreted|||Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3 and VEGFR-2. VEGF-D first form an antiparallel homodimer linked by disulfide bonds before secretion. The fully processed VEGF-D is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions (By similarity). http://togogenome.org/gene/10090:Nlrp9a ^@ http://purl.uniprot.org/uniprot/D3Z7F5|||http://purl.uniprot.org/uniprot/E9QKM4|||http://purl.uniprot.org/uniprot/Q66X03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NLRP family.|||Cytoplasm|||May be involved in inflammation.|||Oocyte specific. http://togogenome.org/gene/10090:Ppp1r21 ^@ http://purl.uniprot.org/uniprot/Q3TDD9 ^@ Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aberrant splicing.|||Early endosome|||Expressed at 16 dpc in the cortex (at protein level).|||Interacts with PPP1CA.|||May be due to intron retention.|||Putative regulator of protein phosphatase 1 (PP1) activity. May play a role in the endosomal sorting process or in endosome maturation pathway. http://togogenome.org/gene/10090:Atp10b ^@ http://purl.uniprot.org/uniprot/A0A571BEJ2|||http://purl.uniprot.org/uniprot/B1AWN4|||http://purl.uniprot.org/uniprot/Q5DU18 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated at the conserved aspartate of the P-type ATPase signature sequence.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of lysosome membranes (By similarity). Plays an important role in the maintenance of lysosome membrane integrity and function in cortical neurons (PubMed:32172343).|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP10B and an accessory beta subunit TMEM30A.|||Endoplasmic reticulum membrane|||Expressed in cortical neuron (at protein level).|||Late endosome membrane|||Lysosome membrane|||Membrane http://togogenome.org/gene/10090:Ube2m ^@ http://purl.uniprot.org/uniprot/G5E919|||http://purl.uniprot.org/uniprot/P61082 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX1, but not RBX2, suggests that the RBX1-UBE2M complex neddylates specific target proteins, such as CUL1, CUL2, CUL3 and CUL4. Involved in cell proliferation.|||Belongs to the ubiquitin-conjugating enzyme family.|||Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily.|||Both the N-terminal docking peptide and the catalytic core domain must bind the UBA3-NAE1 complex simultaneously for optimal transfer of NEDD8.|||Interacts with UBA3 and RBX1. Interacts (N-terminally acetylated form) with (via DCUN1 domain) DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5.|||The acetylation of Met-1 increases affinity for DCUN1D1 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins. http://togogenome.org/gene/10090:Traf2 ^@ http://purl.uniprot.org/uniprot/P39429|||http://purl.uniprot.org/uniprot/Q3U8L1|||http://purl.uniprot.org/uniprot/Q8C6X9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TNF receptor-associated factor family.|||Belongs to the TNF receptor-associated factor family. A subfamily.|||Cytoplasm|||Has very low E3 ubiquitin ligase activity in the absence of sphingosine-1-phosphate. E3 ubiquitin ligase activity is strongly activated by cytoplasmic sphingosine-1-phosphate.|||Homotrimer (By similarity). Heterotrimer with TRAF1 (PubMed:8069916). Heterotrimer with TRAF3 (via TRAF domain) (By similarity). The domain containing the RING-type and the first TRAF-type zinc finger can also form homodimers (in vitro) (By similarity). Interacts with TNFRSF1B/TNFR2 (PubMed:8069916). Interacts with TNFRSF5/CD40 (PubMed:11909853). Interacts with TNFRSF4, TNFRSF7/CD27, TNFRSF8/CD30, TNFRSF9/CD137, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF16/NGFR, TNFRSF17/BCMA, TNFRSF18/AITR, TNFRSF19/TROY, TNFRSF19L/RELT and EDAR (By similarity). Stimulation of TNF-alpha receptor TNFRSF1A leads to the formation of two distinct signaling complexes. Plasma membrane-bound complex I is composed of TNFRSF1A, TRADD, RIPK1, TRAF2 and BIRC2/c-IAP1 or BIRC3 which interacts with CHUCK/IKK-alpha, IKBKB/IKK-beta and IKBKG/IKK-gamma promoting cell survival (PubMed:19150425, PubMed:19815541). Subsequently, TRADD, RIPK1 and TRAF2 dissociate from TNFRSF1A and form cytoplasmic complex II with FADD and caspase CASP8 promoting cell apoptosis (By similarity). Interacts with TRADD (PubMed:8565075). Identified in a complex with TNFRSF1A, RIPK1 and IKBKB/IKK-beta (By similarity). Interacts with RIPK2 (By similarity). Interacts with BIRC2 and BIRC3 N-terminus; a single BIRC2 or BIRC3 molecule interacts with a heterotrimer formed by TRAF1 and TRAF2, or a TRAF2 homotrimer (By similarity). Identified in a complex composed of TRAF2, TRAF3, BIRC2 and BIRC3 (PubMed:18997794). Interacts with BIRC2; the interaction promotes BIRC2 stability (PubMed:19506082). Interaction with BIRC2 and/or BIRC3 is essential for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B (PubMed:19815541). Within complex I, phosphorylated TRAF2 interacts (via 'Lys-63'-linked polyubiquitin chains) with CHUCK/IKK-alpha, IKBKB/IKK-beta, IKBKG/IKK-gamma TAB2, TAB3 and TAK1 in response to TNF-alpha stimulation (PubMed:19150425). Within complex I, interacts with UXT isoform 1 (via TPQE motif); the interaction prevents the recruitment of FADD and CASP8/caspase 8 to complex I (PubMed:21307340). Forms a complex composed of TNFRSF8/CD30 or TNFRSF1B/TNFR2, and TRAF1, TRAF2 and E3 ligase TRAIP (PubMed:9104814). Within the complex, interacts with TRAIP; the interaction inhibits TRAF2-mediated NF-kappa B activation (PubMed:9104814). Component of a complex composed of TANK and TBK1 (By similarity). Interacts with TRPC4AP (PubMed:16876162). Interacts with MAP3K1/MEKK1, MAP3K5/ASK1 and MAP3K11/MLK3 in response to TNF-alpha stimulation; the interaction leads to JNK activation and interaction with MAP3K5 is inhibited by PRMT1 (By similarity). Component of a complex composed of MAP3K14/NIK BIRC3 and TRAF3; the interaction leads to BIRC2/3-mediated ubiquitination of TRAF3 upon CD40 engagement in a TRAF2-dependent manner (PubMed:18997792). Interacts with MAP3K14/NIK in response to TNF-alpha stimulation; the interaction leads to NF-kappa B activation (By similarity). Interacts with PEG3; the interaction may promote TRAF2-mediated NF-kappa B activation (PubMed:9500555). Interacts with HIVEP3; the interaction may inhibit TNF-alpha-TRAF2-mediated NF-kappa B and JNK activation (PubMed:11804591). Interacts with TANK/ITRAF; the interaction prevents interaction between TNFRSF1B/TNFR2 and TRAF2 (By similarity). Interacts with deubiquitinating enzyme CYLD; the interaction results in the deubiquitination and inactivation of TRAF2 (By similarity). Interacts with SIAH2; the interaction leads to TRAF2 ubiquitination and degradation (By similarity). Interacts with E2 conjugating enzyme UBE2N/Ubc13, E3 ligase ITCH and RNF11 in response to TNF-alpha stimulation (By similarity). Interacts with ubiquitin-editing enzyme TNFAIP3/A20 in response to TNF-alpha stimulation; the interaction promotes TRAF2 dissociation from UBE2N/Ubc13, ITCH, RNF11 and TAX1BP1 and prevents prolonged TRAF-2 ubiquitination (PubMed:8692885, PubMed:20185725). Interacts with TAX1BP1 in response to TNF-alpha stimulation; the interaction promotes TRAF2 dissociation from UBE2N/Ubc13 and TNFAIP3/A20, and prevents prolonged TRAF-2 ubiquitination (PubMed:20185725). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). Interacts with deubiquitinating enzyme USP48 (By similarity). Interacts with PTPN2; probably involved in TNF-mediated signaling (By similarity). Interacts with Toll-like receptor TLR4/3 adapter TICAM1/TRIF; the interaction may promote TICAM1 ubiquitination (By similarity). Interacts with kinase/endoribonuclease ERN1/IRE1 and DAB2IP in response to ER stress; the interaction requires DAB2IP (PubMed:18281285). Interacts with ERN1/IRE1 and TAOK3 in response to ER stress; the interaction may promote TRAF2 phosphorylation (By similarity). Interacts (via zinc fingers) with DAB2IP (via C-terminus PER domain) in response to TNF-alpha stimulation (By similarity). Interacts with CASP8AP2/FLASH (PubMed:11340079). Interacts with NFATC2IP; the interaction may repress IL-4 production in T cells (PubMed:11435475). Interacts with kinase CDK9. Interacts with sphingosine kinase 1 SPHK1 (By similarity). Interacts with kinase TNIK (By similarity). Interacts with TRAFD1 (PubMed:18849341). Interacts with DNA phosphodiesterase TDP2 (By similarity). Interacts with MAVS/IPS1. Interacts with CARD14 (By similarity). Interacts with GPS2 (PubMed:22424771). Interacts with XPNPEP3 (By similarity). Interacts with RIPK3 (By similarity). Interacts with RELL2 (By similarity). Interacts with LRRC19 (By similarity). Interacts with GAPDH; promoting TRAF2 ubiquitination (By similarity).|||Important embryonic and perinatal mortality. Life-born mutants appear normal at birth, but are smaller than their littermates after three days, fail to thrive, and few survive more than three weeks. Thymus and spleen are severely atrophic, and mice display lymphopenia of both T and B lymphocytes, with normal erythrocyte counts. Their thymocytes are abnormally sensitive to TNF-induced cell death and exhibit high levels of spontaneous apoptosis. Macrophages are highly sensitive to TNF and produce high levels of nitric oxide (NO) in response to TNF. Likewise, endogenous TNF production is abnormally increased upon exposure to TNF. Symptoms are much attenuated in mice that are deficient for both Traf2 and Tnfrsf1a/Tnfr1, or Traf2 and Tnf. Likewise, deletion of one Map3k14 allele alleviates symptoms and rescues splenic atrophy and reduction of splenocyte numbers. Mice show normal IgM production in response to viral infection, but lack CD40-mediated proliferation of B-cells. They are deficient in antibody isotype switching and fail to produce IgG.|||Isoform 1 and isoform 2 are expressed in spleen, adipose tissues, skeletal muscles, thymus, testis, heart, lung, brain. Isoform 2 is very weakly expressed in heart, lung and brain.|||On mRNA level, has a significantly shorter half-life than isoform 1.|||Phosphorylated at several serine residues within the first 128 amino acid residues. Phosphorylated at Thr-117 in response to signaling via TNF and TNFRSF1A. Phosphorylation at Thr-117 is required for 'Lys-63'-linked polyubiquitination, but not for 'Lys-48'-linked polyubiquitination. Phosphorylation at Thr-117 is important for interaction with IKKA and IKKB, activation of IKK and subsequent activation of NF-kappa-B.|||Regulates activation of NF-kappa-B and JNK and plays a central role in the regulation of cell survival and apoptosis. Required for normal antibody isotype switching from IgM to IgG. Has E3 ubiquitin-protein ligase activity and promotes 'Lys-63'-linked ubiquitination of target proteins, such as BIRC3, RIPK1 and TICAM1. Is an essential constituent of several E3 ubiquitin-protein ligase complexes, where it promotes the ubiquitination of target proteins by bringing them into contact with other E3 ubiquitin ligases. Regulates BIRC2 and BIRC3 protein levels by inhibiting their autoubiquitination and subsequent degradation; this does not depend on the TRAF2 RING-type zinc finger domain. Isoform 2 does not seem to mediate activation of NF-kappa-B but inhibits isoform 1 activity. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR. In complex with BIRC2 or BIRC3, promotes ubiquitination of IKBKE.|||The MATH/TRAF domain binds to receptor cytoplasmic domains.|||The RING-type zinc finger domain is essential for E3 ubiquitin-protein ligase activity. It is not essential for the stabilization of BIRC2, or for the ubiquitination of RIPK1 in response to TNFR1 signaling.|||The coiled coil domain mediates homo- and hetero-oligomerization.|||Undergoes both 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination. Polyubiquitinated via 'Lys-63'-linked ubiquitin in response to TNF signaling; this requires prior phosphorylation at Thr-117. 'Lys-63'-linked polyubiquitination promotes TRAF2-mediated activation of NF-kappa-B. Can be polyubiquitinated at several Lys residues via 'Lys-48'-linked ubiquitin chains in response to TNF signaling, leading to proteasomal degradation. Autoubiquitinated, leading to its subsequent proteasomal degradation. Polyubiquitinated by BIRC2 and SIAH2, leading to its subsequent proteasomal degradation. Not ubiquitinated by BIRC3 or SIAH1. Deubiquitinated by CYLD, a protease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Ubiquination is inhibited by LRRC19; inhiits proteasomal degradation (PubMed:25026888). Ubiquitinated at Lys-320 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:23542741). Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to repression of NF-kappa-B signaling (By similarity). http://togogenome.org/gene/10090:Vmn1r204 ^@ http://purl.uniprot.org/uniprot/I7HIK1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxo11 ^@ http://purl.uniprot.org/uniprot/Q7TPD1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc and 10.5 dpc, expression is restricted to developing heart tissue. By 11.5 dpc and 12.5 dpc, detected in liver and subsequently in muscle by 13.5 dpc. At 14.5 dpc, still detected in heart, liver and muscle and also in the developing secondary palate including the nasal, medial and oral epithelia of the palatal shelves. At 15.5 dpc and 16.5 dpc, expressed in lung, kidney, heart, liver, muscle and adrenal gland. At this time, fusion of the palate shelves has occurred, with expression confined to the nasal and oral epithelia. At 17.5 dpc, expression in the lung is confined to bronchial epithelial cells and is evident in bone marrow, skin, tissue macrophages, osteoblasts, kidney, liver and spleen. At 18.5 dpc, expressed in bone marrow, liver, kidney and muscle but decreases in heart and lung. At this time, first detected in the middle ear epithelium. At the newborn stage, expression is strong in the middle ear where it is confined to mucin-secreting cells, as well as persisting in bone marrow, kidney and liver. Middle ear expression persists in postnatal head tissue at 4 and 13 days after birth and has declined by 21 days after birth. In the adult, expression is seen in alveolar macrophages of the lung, glomeruli and collecting tubules of the kidney, midbrain, heart and muscle.|||Chromosome|||Component of the SCF(FBXO11) complex consisting of CUL1, RBX1, SKP1 and FBXO11. Interacts with p53/TP53, BCL6 and DTL (when not phosphorylated). Interacts with PRMD1. Interacts with TRAF3. Interacts with CIITA. Interacts with BAHD1.|||Not detected at 8.5 dpc. Expressed from 9.5 dpc throughout development and into adulthood (at protein level).|||Nucleus|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. The SCF(FBXO11) complex mediates ubiquitination and degradation of BCL6, thereby playing a role in the germinal center B-cells terminal differentiation toward memory B-cells and plasma cells. The SCF(FBXO11) complex also mediates ubiquitination and degradation of DTL, an important step for the regulation of TGF-beta signaling, cell migration and the timing of the cell-cycle progression and exit. Binds to and neddylates phosphorylated p53/TP53, inhibiting its transcriptional activity. Plays a role in the regulatiom of erythropoiesis but not myelopoiesis or megakaryopoiesis. Mechanistically, activates erythroid genes by mediating the degradation of BAHD1, a heterochromatin-associated protein that recruits corepressors to H3K27me3 marks. Participates in macrophage cell death and inflammation in response to bacterial toxins by regulating the expression of complement 5a receptor 1/C5AR1 and IL-1beta. Acts as a critical regulator to determine the level of MHC-II by mediating the recognition of degron at the P/S/T domain of CIITA leading to its ubiquitination and subsequent degradation via the proteasome. Participates in the antiviral repsonse by initiating the activation of TBK1-IRF3-IFN-I axis. Mediates the 'Lys-63'-linked ubiquitination of TRAF3 to strengthen the interaction between TRAF3 and TBK1. http://togogenome.org/gene/10090:Tomm5 ^@ http://purl.uniprot.org/uniprot/B1AXP6 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tom5 family.|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70).|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Emx1 ^@ http://purl.uniprot.org/uniprot/Q04742 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EMX homeobox family.|||Cerebral cortex. Expressed in the olfactory bulbs.|||Detectable from 9.5 dpc.|||Interacts with WRD11 (via the N-terminal and the central portion of the protein); the interaction associates EMX1 with GLI3.|||Nucleus|||Transcription factor, which in cooperation with EMX2, acts to generate the boundary between the roof and archipallium in the developing brain. May function in combinations with OTX1/2 to specify cell fates in the developing central nervous system. http://togogenome.org/gene/10090:Or10h1b ^@ http://purl.uniprot.org/uniprot/K7N6Q1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sec24b ^@ http://purl.uniprot.org/uniprot/Q80ZX0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SEC23/SEC24 family. SEC24 subfamily.|||COPII-coated vesicle membrane|||Endoplasmic reticulum membrane|||Membrane|||cytosol http://togogenome.org/gene/10090:B230219D22Rik ^@ http://purl.uniprot.org/uniprot/Q80X32 ^@ Similarity ^@ Belongs to the UPF0461 family. http://togogenome.org/gene/10090:Nisch ^@ http://purl.uniprot.org/uniprot/Q80TM9 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Nischarin' means 'slowness of motion' in classic Sanskrit.|||Acts either as the functional imidazoline-1 receptor (I1R) candidate or as a membrane-associated mediator of the I1R signaling. Binds numerous imidazoline ligands that induces initiation of cell-signaling cascades triggering to cell survival, growth and migration. Its activation by the agonist rilmenidine induces an increase in phosphorylation of mitogen-activated protein kinases MAPK1 and MAPK3 in rostral ventrolateral medulla (RVLM) neurons that exhibited rilmenidine-evoked hypotension (By similarity). Blocking its activation with efaroxan abolished rilmenidine-induced mitogen-activated protein kinase phosphorylation in RVLM neurons (By similarity). Acts as a modulator of Rac-regulated signal transduction pathways. Suppresses Rac1-stimulated cell migration by interacting with PAK1 and inhibiting its kinase activity. Also blocks Pak-independent Rac signaling by interacting with RAC1 and inhibiting Rac1-stimulated NF-kB response element and cyclin D1 promoter activation. Inhibits also LIMK1 kinase activity by reducing LIMK1 'Tyr-508' phosphorylation. Inhibits Rac-induced cell migration and invasion in breast and colon epithelial cells. Inhibits lamellipodia formation, when overexpressed. Plays a role in protection against apoptosis (By similarity). Involved in association with IRS4 in the enhancement of insulin activation of MAPK1 and MAPK3 (By similarity). When overexpressed, induces a redistribution of cell surface ITGA5 integrin to intracellular endosomal structures (By similarity).|||Both the presence of the PX domain and the coiled coil region are necessary for its endosomal targeting.|||Cell membrane|||Cytoplasm|||Early endosome|||Expressed in embryo at 7 day dpc onwards.|||Highly expressed in brain and kidney. Moderately expressed in heart, liver, lung and skeletal muscle. Not detected in spleen and testis.|||Homooligomer (By similarity). Interacts with GRB2 (By similarity). Interacts with PIK3R1; probably associates with the PI3-kinase complex (By similarity). Interacts with IRS4 (By similarity). Found in a complex with ITGA5 and PAK1. Found in a complex with LIMK1 and PAK1. Interacts with ITGA5 (via cytoplasmic domain); this interaction is direct. Interacts with PAK1 (via kinase domain); this interaction is direct and is increased upon activation of PAK1. Interacts with LIMK1 (via PDZ and kinase domain); this interaction is direct. Interacts with LIMK2; this interaction depends on LIMK2 activity. Interacts with RAC1 (activated state). Interacts with STK11; this interaction may increase STK11 activity (By similarity).|||Recycling endosome http://togogenome.org/gene/10090:Slitrk2 ^@ http://purl.uniprot.org/uniprot/Q810C0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLITRK family.|||Cell membrane|||In the adult, significant expression is detected only in the brain. Broadly expressed in embryonic brain with highest expression in ventricular layer, subventricular zone, cortical plate, pyramidal layer of hippocampus, subicular neuroepithelium, thalamus, hypothalamus and spinal cord.|||In the embryo, expressed from day 9-12 and continues through later gestational development and into adulthood.|||Interacts with PTPRD; this interaction is PTPRD splicing-dependent and may induce pre-synaptic differentiation.|||It is involved in synaptogenesis (PubMed:25989451). Promotes excitatory synapse differentiation (By similarity). Suppresses neurite outgrowth (PubMed:14550773).|||Membrane http://togogenome.org/gene/10090:Fbxl4 ^@ http://purl.uniprot.org/uniprot/Q8BH70 ^@ Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Mitochondrion|||Nucleus|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. http://togogenome.org/gene/10090:Uox ^@ http://purl.uniprot.org/uniprot/P25688|||http://purl.uniprot.org/uniprot/Q543J0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Acetylation of Lys-118, Lys-164 and Lys-290 is observed in liver mitochondria from fasted mice but not from fed mice. May be deacetylated by Sirt5; however it is unclear whether Sirt5 mediates deacetylation or desuccinylation of Uox; additional evidence is required to validate these results (PubMed:23085393).|||Belongs to the uricase family.|||Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.|||Mitochondrion|||Peroxisome http://togogenome.org/gene/10090:Ccng2 ^@ http://purl.uniprot.org/uniprot/O08918|||http://purl.uniprot.org/uniprot/Q3TG40|||http://purl.uniprot.org/uniprot/Q5HZK4 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated in B-cells by agents causing growth inhibition or growth arrest.|||Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin G subfamily.|||Cytoplasm|||Expression levels oscillate moderately through the cell cycle.|||Highest levels in intestine. Intermediate levels in spleen, brain and kidney. Low levels in testis, stomach, pancreas, liver, salivary gland and muscle. According to PubMed:9139721 also abundant in thymus.|||May play a role in growth regulation and in negative regulation of cell cycle progression.|||Nucleus http://togogenome.org/gene/10090:Mrrf ^@ http://purl.uniprot.org/uniprot/Q9D6S7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RRF family.|||Mitochondrion|||Responsible for the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with GFM2. Promotes mitochondrial ribosome recycling by dissolution of intersubunit contacts. http://togogenome.org/gene/10090:Tmem51 ^@ http://purl.uniprot.org/uniprot/Q99LG1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Frrs1l ^@ http://purl.uniprot.org/uniprot/B1AXV0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Component of the outer core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.|||Expressed in 12.5 dpc embryos.|||Expressed in the brain (at protein level) (PubMed:22632720). In embryos expression is evident in the ventral forebrain, but a lower level is seen in the remainder of the embryos. In the adult brain, expressed in the cortex, cerebellum, hippocampus and basal ganglia (PubMed:27236917).|||Important modulator of glutamate signaling pathway.|||Synapse http://togogenome.org/gene/10090:Kbtbd8 ^@ http://purl.uniprot.org/uniprot/Q3UQV5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KBTBD8 family.|||Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1.|||Down-regulated in differentiating embryonic stem cells (ESCs).|||Golgi apparatus|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification. The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1: monoubiquitination promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification.|||spindle http://togogenome.org/gene/10090:Nupr1 ^@ http://purl.uniprot.org/uniprot/Q9WTK0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated.|||At 14 dpc, highly expressed in brain and the highest level is detected at 16 dpc and 18 dpc. Following birth, levels are barely detectable and stabilize at low levels starting at 20 pnd through adulthood.|||Belongs to the NUPR family.|||Cytoplasm|||Highly expressed in pancreas and both ovaries and testes.|||Knockout NUPR1 mice are viable and seem normal. Mouse embryonic fibroblast grown more rapidly compared to wild type (PubMed:11896600). Knockout NUPR1 mice are fertile. However female present a delay in female sexual maturation and male develop a phenotype similar to Sertoli-cell-only syndrome (SCOS) (PubMed:18495683).|||Monomer. Directly interacts with MSL1 and binds MORF4L1, two components of histone acetyltransferase complex; the interaction with MORF4L1 may be mediated by MSL1. Interacts with EP300; this interaction enhances the effect of EP300 on PAX2 transcription factor activity. Interacts with PAXIP1; this interaction prevents PAXIP1 inhibition of PAX2 transcription factor activity. Interacts with COPS5; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation. Interacts with RNF2. Interacts with FOXO3; this interaction represses FOXO3 transactivation. Interacts with PTMA; regulates apoptotic process (By similarity). Interacts with MYOD1, EP300 and DDX5; this interaction coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter (PubMed:19723804). Interacts with TP53; interaction is stress-dependent. Forms a complex with EP300 and TP53; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity).|||Nucleus|||Phosphorylated. Phosphorylation promotes DNA-binding activity.|||Transcription regulator that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Thereby participates in regulation of many process namely cell-cycle, apoptosis, autophagy and DNA repair responses (PubMed:11896600, PubMed:19723804, PubMed:23900510, PubMed:27451286, PubMed:22565310, PubMed:20181828). Controls cell cycle progression and protects cells from genotoxic stress induced by doxorubicin through the complex formation with TP53 and EP300 that binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity). Protects pancreatic cancer cells from stress-induced cell death by binding the RELB promoter and activating its transcription, leading to IER3 transactivation (PubMed:22565310). Negatively regulates apoptosis through interaction with PTMA (By similarity). Inhibits autophagy-induced apoptosis in cardiac cells through FOXO3 interaction, inducing cytoplasmic translocation of FOXO3 thereby preventing the FOXO3 association with the pro-autophagic BNIP3 promoter (PubMed:20181828). Inhibits cell growth and facilitates programmed cell death by apoptosis after adriamycin-induced DNA damage through transactivation of TP53 (PubMed:11896600). Regulates methamphetamine-induced apoptosis and autophagy through DDIT3-mediated endoplasmic reticulum stress pathway (By similarity). Participates in DNA repair following gamma-irradiation by facilitating DNA access of the transcription machinery through interaction with MSL1 leading to inhibition of histone H4' Lys-16' acetylation (H4K16ac) (By similarity). Coactivator of PAX2 transcription factor activity, both by recruiting the EP300 cofactor to increase PAX2 transcription factor activity and by binding PAXIP1 to suppress PAXIP1-induced inhibition on PAX2 (By similarity). Positively regulates cell cycle progression through interaction with COPS5 inducing cytoplasmic translocation of CDKN1B leading to the CDKN1B degradation (By similarity). Coordinates, through its interaction with EP300, the assiociation of MYOD1, EP300 and DDX5 to the MYOG promoter, leading to inhibition of cell-cycle progression and myogenic differentiation promotion (PubMed:19723804). Negatively regulates beta cell proliferation via inhibition of cell-cycle regulatory genes expression through the suppression of their promoter activities (PubMed:23900510). Also required for LHB expression and ovarian maturation (PubMed:18495683). Exacerbates CNS inflammation and demyelination upon cuprizone treatment (PubMed:16374777).|||Transiently induced in G1 phase (PubMed:19723804). Activated in fibroblasts during growth arrest. Rapidly induced in response to adriamycin-induced apoptosis. Inhibited by TP53 (PubMed:11896600). Up-regulated during cuprizone-induced inflammation and demyelination (PubMed:16374777).|||perinuclear region http://togogenome.org/gene/10090:Smg9 ^@ http://purl.uniprot.org/uniprot/Q9DB90 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the SMG9 family.|||Embryonic lethal. Homozygous null embryos show a range of abnormalities, including edema, hemorrhage, exencephaly, preaxial polydactyly, decreased size of the mid- and hindbrains, microphthalmia, thin myocardium, and cardiac septal defects. These phenotypes are variable among mutant embryos; there is evidence of incomplete penetrance, but most embryos show clear phenotypic abnormalities.|||Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8 (By similarity). Plays a role in brain, heart, and eye development (PubMed:27018474).|||Phosphorylated by SMG1.|||Self-associates to form homodimers and forms heterodimers with SMG8; these assembly forms may represent SMG1C intermediate forms (By similarity). Component of the SMG1C complex composed of SMG1, SMG8 and SMG9 (By similarity). Interacts with DHX34; the interaction is RNA-independent (By similarity). http://togogenome.org/gene/10090:Vps18 ^@ http://purl.uniprot.org/uniprot/Q8R307 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS18 family.|||Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuole/endosome tethering (CORVET) complex. Their common core is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1. Interacts with RAB5C (PubMed:25266290). Interacts with HOOK1 (PubMed:14668490). Interacts with STX7, MON1B (By similarity). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (PubMed:21411634). Interacts with SYNPO2 (By similarity). Interacts with PLEKHM1 (By similarity).|||Early endosome|||Late endosome membrane|||Lysosome membrane|||Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (By similarity). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:14517315, PubMed:22854957). Involved in dendrite development of Pukinje cells (PubMed:22699122).|||autophagosome|||clathrin-coated vesicle http://togogenome.org/gene/10090:Tubgcp2 ^@ http://purl.uniprot.org/uniprot/Q3UIT6|||http://purl.uniprot.org/uniprot/Q921G8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TUBGCP family.|||Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6. Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome.|||Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.|||Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome. Plays a role in neuronal migration.|||centrosome http://togogenome.org/gene/10090:Smg7 ^@ http://purl.uniprot.org/uniprot/Q5RJH6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Nucleus|||Part of a complex that contains SMG5, SMG7, PPP2CA, a short isoform of UPF3A (isoform UPF3AS, but not isoform UPF3AL) and phosphorylated UPF1 (By similarity). Interacts with DHX34; the interaction is RNA-independent (By similarity).|||Plays a role in nonsense-mediated mRNA decay. Recruits UPF1 to cytoplasmic mRNA decay bodies. Together with SMG5 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation (By similarity). http://togogenome.org/gene/10090:Atp5mpl ^@ http://purl.uniprot.org/uniprot/P56379 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small mitochondrial proteolipid family.|||Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL.|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Minor subunit required to maintain the ATP synthase population in the mitochondria.|||Mitochondrion membrane http://togogenome.org/gene/10090:Adcy2 ^@ http://purl.uniprot.org/uniprot/Q3V1Q3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.|||Membrane http://togogenome.org/gene/10090:Hmox2 ^@ http://purl.uniprot.org/uniprot/O70252|||http://purl.uniprot.org/uniprot/Q544R7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A soluble form arises by proteolytic removal of the membrane anchor.|||Belongs to the heme oxygenase family.|||Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.|||Endoplasmic reticulum membrane|||Microsome membrane|||Ubiquitous. http://togogenome.org/gene/10090:Abca1 ^@ http://purl.uniprot.org/uniprot/P41233|||http://purl.uniprot.org/uniprot/Q8BPY1 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylcholine and to a lesser degree by phosphatidylserine and sphingomyelin. Phospholipid translocase activity is highly reduced by berylium fluoride and aluminum flouride and reduced by N-ethylmaleimide.|||Belongs to the ABC transporter superfamily. ABCA family.|||Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs. Transports preferentially phosphatidylcholine over phosphatidylserine. May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs. Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain.|||Cell membrane|||Down-regulated by endotoxins (LPS) or cytokines (TNF and IL-1) in J774 macrophages. The down-regulation by endotoxin in macrophages is not likely to be mediated by the liver X receptor/retinoic X receptor (LXR/RXR).|||Endosome|||Interacts with MEGF10 (PubMed:17205124). May interact with APOE1; functionally associated with APOE1 in the biogenesis of HDLs (By similarity). Interacts with ABCA8; this interaction potentiates cholesterol efflux (By similarity). Interacts with ABCA12 and NR1H2; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability (By similarity).|||Membrane|||Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.|||Palmitoylated by ZDHHC8. Palmitoylation is essential for localization to the plasma membrane.|||Phosphorylation on Ser-2054 regulates phospholipid efflux.|||Widely expressed in adult tissues. Highest levels are found in pregnant uterus and uterus. http://togogenome.org/gene/10090:Slirp ^@ http://purl.uniprot.org/uniprot/Q9D8T7 ^@ Function|||Subcellular Location Annotation ^@ Mitochondrion|||Nucleus|||RNA-binding protein that acts as a nuclear receptor corepressor. Probably acts by binding the SRA RNA, and repressing the SRA-mediated nuclear receptor coactivation. Binds the STR7 loop of SRA RNA. Also able to repress glucocorticoid (GR), androgen (AR), thyroid (TR) and VDR-mediated transactivation (By similarity). http://togogenome.org/gene/10090:Dmpk ^@ http://purl.uniprot.org/uniprot/E9Q6J9|||http://purl.uniprot.org/uniprot/P54265 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.|||Cell membrane|||Coiled-coil-mediated oligomerization enhances the catalytic activity. Proteolytic processing of the C-terminus may release the protein from membranes and constitute a mean to regulate the enzyme. May be regulated by HSPB2, RAC1, RAF1 and G-protein second messengers (By similarity).|||Endoplasmic reticulum membrane|||Expressed in all tissues tested, with a predominance in brain, skeletal muscle, heart, and other tissues containing smooth muscle. In the heart, expression is restricted to the cardiomyocytes in the ventricle and atrium.|||Homodimer; homodimerization stimulates the kinase activity. Interacts with HSPB2; may enhance DMPK kinase activity. Interacts with PLN; phosphorylates PLN. May interact with RAC1; may regulate DMPK kinase activity. Interacts with LMNA; may regulate nuclear envelope stability (By similarity).|||Mice are fertile and no negative selection against the absence of the protein is apparent. Newborn do not display hypotonia, respiratory distress or gross anatomical abnormalities. However, a progressive muscle weakness a hall mark of myopathies is observed. Muscles from mature mice show variation in fiber size, increase fiber degeneration and fibrosis. They also display age-related progression in atrioventricular conduction defects that are reminiscent of congenital myotonic dystrophy.|||Mitochondrion outer membrane|||Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.|||Nucleus outer membrane|||Phosphorylated. Autophosphorylates. Phosphorylation by RAF1 may result in activation of DMPK (By similarity).|||Primarily detected in striated muscle structures of the 14.5 day embryo, including all major muscles in the skeletal structures, cardiac muscle, diaphragm, and the smooth muscle of the lung and gut.|||Proteolytic processing of the C-terminus may remove the transmembrane domain and release the kinase from membranes stimulating its activity.|||Sarcoplasmic reticulum membrane|||The coiled coil domain is required for homodimerization and regulates the enzymatic activity.|||cytosol http://togogenome.org/gene/10090:Rest ^@ http://purl.uniprot.org/uniprot/Q8VIG1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than isoform 1 (PubMed:11039732). Exhibits weaker repressor activity compared to isoform 1 (By similarity). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11039732, PubMed:10490617). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (By similarity). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 2 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes, maintenance of hair cells and hearing (PubMed:29961578).|||Contaminating sequence. Potential poly-A sequence.|||Controversial data exists concerning the repressor activity of isoform 2. A study in human showed that human isoform 3 exhibits weak repressor activity of a NRSE motif-containing reporter construct (By similarity). Another report, however, does not observe any isoform 3 transcriptional repressor activity of a NRSE motif-containing reporter construct (By similarity). Controversial data also exists regarding the function of isoform 2 on the negative regulation of full-length REST. It was shown that isoform 2 negatively regulates the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:10490617, PubMed:11039732). Another study in human, however, did not observe any inhibitory activity of human isoform 3 on the isoform 1 repressor activity (By similarity).|||Cytoplasm|||Down-regulated in differentiating neurons and mature neurons.|||Embryonic lethality by embryonic day 11.5 dpc (PubMed:9771705). At 9.25 dpc, disorganization of the head mesenchyme in the midbrain region with separation of myotomal cells from the dermomyotome and widespread apoptotic cell death (PubMed:9771705). Forebrain malformation and widening of the mesencephalic flexure at 9.5 dpc and 10.5 dpc, and growth retardation by 10.5 dpc (PubMed:9771705). Conditional knockout in the nervous system results in a progressive age-related neurodegenerative phenotype (PubMed:24670762). At the age of 1 month, no change of neuronal numbers in the cortex and hippocampus, but at the age of 8 months, neuronal degeneration and apoptosis, accompanied by significant neuronal loss in the cerebral cortex and hippocampus, and pronounced gliosis (PubMed:24670762). In primary 16 dpc cortical neurons, increased degeneration and cell death upon oxidative stress or exposure to oligomeric amyloid-beta 42 (PubMed:24670762). Conditional knockout in QNP cells leads to a higher number of proliferating QNP cells, an increased transition to TAP cells and increased differentiation into mature neurons (PubMed:27819263). Conditional knockdout in proliferating cells leads to a decreased number of proliferating TAP cells and an increase in immature and mature neurons (PubMed:27819263).|||Expressed in the hippocampus, including quiescent neuronal progenitor (QNP) cells, transient-amplifying progenitor (TAP) cells, neuroblasts and mature neurons (at protein level) (PubMed:27819263). Expressed in embryonic stem cells (at protein level) (PubMed:15907476). Expressed in many non-neuronal tissues including the heart and liver (PubMed:7871435). Abundantly expressed in osteoblastic lineage cells (PubMed:25727884). Expressed in the spleen, kidney, blood cells, cortex, neocortex and in the utricle, saccule and organ of Corti of the inner ear (PubMed:29961578). Isoform 2: Expressed in the cortex, neocortex and in the utricle, saccule and organ of Corti of the inner ear (PubMed:29961578).|||Isoform 1 and isoform 2 form heterodimers (PubMed:10490617). Isoform 2: Forms homodimers and homooligomers; binds to the neuron-restrictive silencer element (NRSE) as monomer (PubMed:11039732). Interacts with SIN3A, SIN3B and RCOR1 (By similarity). Interacts with CDYL (By similarity). Interacts with EHMT1 and EHMT2 only in the presence of CDYL (By similarity). Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). Interacts (via zinc-finger DNA-binding domain) with ZFP90 (via N- and C-termini); the interaction inhibits REST repressor activity (PubMed:21284946). Interacts (via C2H2-type zinc finger 5) with PRICKLE1 (By similarity). Interacts with FBXW11 and BTRC (By similarity). Interacts with USP7 (By similarity).|||Nucleus|||O-glycosylated.|||Phosphorylated; phosphorylation is required for ubiquitination.|||Produced by SRRM4-dependent alternative splicing in neurons and inner ear hair cells (PubMed:11039732, PubMed:29961578). Lacks the four C-terminal zinc fingers and the RCOR1 corepressor interaction site found in full length REST isoform 1, which are required for full DNA-binding and repressive activity (PubMed:11039732, PubMed:29961578).|||The C2H2-type zinc finger 5 is required for nuclear localization.|||Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:29961578, PubMed:9771705). Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes (By similarity). Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (By similarity). Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 2 (PubMed:21884984). Repressor activity may be inhibited by forming heterodimers with isoform 2, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes (PubMed:10490617, PubMed:11039732). Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes (PubMed:15907476). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:27819263). Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits (By similarity). Acts as a regulator of osteoblast differentiation (PubMed:25727884). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions (By similarity). May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response (PubMed:24670762). Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death (By similarity). After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death (By similarity).|||Ubiquitinated; ubiquitination is mediated by BTRC and leads to proteasomal degradation in G2 phase (By similarity). Ubiquitination increases during neuronal differentiation (By similarity). Deubiquitinated by USP7; leading to its stabilization and promoting the maintenance of neural progenitor cells (By similarity).|||Ubiquitously expressed in 8.5 dpc and 9.5 dpc embryos (PubMed:9771705). During embryogenesis, expressed at high levels in non-neuronal and differentiated peripheral nervous tissues, but is not expressed in differentiating neurons in the CNS (PubMed:7697725, PubMed:7871435). Expressed in the neocortex at embryonic stage 14.5 dpc and 16 dpc and in the utricle at 15.5 dpc (PubMed:29961578). Isoform 2: Expressed in the neocortex at embryonic stage 14.5 dpc and 16 dpc and in the utricle and saccule at 16 dpc (PubMed:29961578). http://togogenome.org/gene/10090:Serbp1 ^@ http://purl.uniprot.org/uniprot/Q3UEI6|||http://purl.uniprot.org/uniprot/Q3UMP4|||http://purl.uniprot.org/uniprot/Q9CY58 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with mature 80S ribosomes (PubMed:34815424). Interacts with EEF2/eEF2; interaction sequesters EEF2/eEF2 at the A-site of the ribosome, thereby blocking the interaction sites of the mRNA-tRNA complex, promoting ribosome stabilization and hibernation (PubMed:34815424). Interacts with SPIN1 (PubMed:23894536). Interacts with CHD3 and TDRD3. Interacts with ZDHHC17 (via ANK repeats) (By similarity).|||Belongs to the SERBP1-HABP4 family.|||Cytoplasm|||May be due to intron retention.|||Nucleus|||Phosphorylation by MTOR inhibits SERBP1 and relieves ribosome hibernation.|||Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:34815424). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (PubMed:34815424). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay (By similarity). Seems to play a role in PML-nuclear bodies formation (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Dusp26 ^@ http://purl.uniprot.org/uniprot/Q9D700 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Brain and skeletal muscle. In the brain it is expressed ubiquitously except in the hippocampus.|||Cytoplasm|||Golgi apparatus|||Inactivates MAPK1 and MAPK3 which leads to dephosphorylation of heat shock factor protein 4 and a reduction in its DNA-binding activity.|||Interacts with HSF4.|||Nucleus http://togogenome.org/gene/10090:Slc9a8 ^@ http://purl.uniprot.org/uniprot/A2A464|||http://purl.uniprot.org/uniprot/Q8R4D1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Expression is much higher in the stomach and jejunum in young mice compared with adult mice.|||Golgi apparatus membrane|||Na(+)/H(+) antiporter. Mediates the electoneutral exchange of intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry. Acts as an Na(+)/H(+) exchanger in the trans-Golgi. Contributes to the regulation of pH regulation of Golgi apparatus, and consequently, in protein trafficking and endosomal morphology (By similarity). Plays a crucial role in germ cells in acrosome biogenesis and sperm development, probably by playing a role in the fusion of the Golgi-derived vesicles that form the acrosomal cap (PubMed:28476888, PubMed:25472965). Can also be active at the cell surface of specialized cells. In the small intestine, plays a major physiological role in transepithelial absorption of Na(+). Regulates intracellular pH homeostasis of intestinal epithelial cells (By similarity). Acts as an important regulator of mucosal integrity in the intestine and in the stomach, could mediate the pH fluctuation necessary for mucin exocytosis or assist membrane trafficking of other proteins (PubMed:26505975, PubMed:23657568, PubMed:23220221). Plays a role in photoreceptor survival and in the maintenance of intracellular pH homeostasis in retinal pigment epithelium (RPE cells) (PubMed:29958869, PubMed:25377091).|||Predominantly expressed in the liver, skeletal muscle, kidney, and testis (PubMed:12409279). Expressed in both renal cortex and medulla (PubMed:12409279). Detected throughout the entire gastrointestinal tract, with high expression detected in stomach, duodenum and ascending colon (PubMed:18209477). In gastric epithelium; expressed in the glands within the fundus and pylorus regions (PubMed:23220221).|||The deficient mice have no obvious intestinal phenotype, show no defect in Na(+)-absorption, have normal serum Na(+) levels and no signs of diarrhea. Apically expressed Slc9a2 and Slc9a3 are increased in the small intestine of the Slc9a8-deficient mice in compensation (PubMed:22575219). Deficient mice have a reduced gastric mucosal surface pH, a higher incidence of developing gastric ulcer, and a decreased of mucin-2 (Muc2) expression (PubMed:23657568, PubMed:23220221). The intestinal mucosa in Slc9a8-deficient mice is prone to bacterial adhesion and penetration, which in turn promotes inflammation (PubMed:26505975, PubMed:23220221). Male knockout mice are infertile, have small testis, low testosterone levels, normal LH and FSH serum levels, however LH receptor (Lhcgr) is approximately 50% reduced. The spermatogenesise is also affected, deficient mice have round-headed spermatozoa and lack acrosomes (PubMed:25472965, PubMed:28476888). Knockout mice exhibit reduced tear production and increased corneal staining (PubMed:25377091). Knockdown Slc9a8 in adult retina leads to photoreceptor cell death (PubMed:25377091, PubMed:29958869).|||acrosome|||multivesicular body membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gm14137 ^@ http://purl.uniprot.org/uniprot/Q8CE97 ^@ Subcellular Location Annotation ^@ Mitochondrion http://togogenome.org/gene/10090:Or4a71 ^@ http://purl.uniprot.org/uniprot/Q8VGM7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Senp6 ^@ http://purl.uniprot.org/uniprot/F6Z9A1|||http://purl.uniprot.org/uniprot/Q6P7W0 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C48 family.|||Interacts with RXRA. Forms a complex with KAT5-TIP60 and UBE2I in response to UV irradiation. Interacts with RPA1 to maintain it in hyposumoylated state during S phase preventing DNA repair initiation (By similarity).|||Nucleus|||Probable cloning artifact.|||Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Desumoylates also RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. http://togogenome.org/gene/10090:Rae1 ^@ http://purl.uniprot.org/uniprot/Q8C570 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat rae1 family.|||Cytoplasm|||Interacts with NUMA1 (via N-terminal end of the coiled-coil domain); this interaction promotes spindle formation in mitosis (By similarity). Interacts with NUP98 (PubMed:10209021). Interacts with MYCBP2 (By similarity). Interacts with USP11 (By similarity).|||Nucleus|||Plays a role in mitotic bipolar spindle formation. Binds mRNA. May function in nucleocytoplasmic transport and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton.|||spindle pole http://togogenome.org/gene/10090:Arhgef38 ^@ http://purl.uniprot.org/uniprot/Q80VK6 ^@ Function ^@ May act as a guanine-nucleotide releasing factor. http://togogenome.org/gene/10090:Or56a3b ^@ http://purl.uniprot.org/uniprot/Q3SXH8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Serpinb11 ^@ http://purl.uniprot.org/uniprot/Q9CQV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Expressed in eye, lung, lymphocytes, thymus, stomach, uterus, heart, brain, liver, skeletal muscle, and in day 7, 15, and 17 embryos.|||Inhibitor of serine proteases. Has moderate inhibitory activity for trypsin-like peptidases, but also some activity with cysteine peptidases, cathepsin L, K, and V, and the serine peptidase, tryptase gamma. http://togogenome.org/gene/10090:Rdm1 ^@ http://purl.uniprot.org/uniprot/Q9CQK3 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ C-terminal half contains cytoplasmic retention domains as well as determinants involved in its stress-induced nucleolar accumulation.|||Cajal body|||Cytoplasm|||Homodimer.|||May confer resistance to the antitumor agent cisplatin. Binds to DNA and RNA (By similarity).|||Nucleus|||PML body|||nucleolus http://togogenome.org/gene/10090:Acot2 ^@ http://purl.uniprot.org/uniprot/Q6P2K2|||http://purl.uniprot.org/uniprot/Q9QYR9 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:25114170). Displays higher activity toward long chain acyl CoAs (C14-C20) (PubMed:25114170). The enzyme is involved in enhancing the hepatic fatty acid oxidation in mitochondria (PubMed:25114170).|||Highly expressed in brown and white adipose tissue, muscle, heart, kidney, lung, adrenal gland and spleen; weakly expressed in intestine, testis and brain.|||In the liver, by peroxisome proliferator (Clofibrate) treatment, via the peroxisome proliferator-activated receptors (PPARs) or fasting for 24 hours.|||Mitochondrion matrix|||Monomer. http://togogenome.org/gene/10090:Uba5 ^@ http://purl.uniprot.org/uniprot/Q8VE47 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin-activating E1 family. UBA5 subfamily.|||Cytoplasm|||Death at embryonic day 12.5 (PubMed:20018847, PubMed:21304510). Embryonic lethality is caused by severe anemia associated with defective differentiation of both megakaryocytes and erythrocytes from common myeloid progenitors (PubMed:21304510).|||E1-like enzyme which specifically catalyzes the first step in ufmylation (PubMed:21304510). Activates UFM1 by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a UFM1-E1 thioester and free AMP (By similarity). Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (By similarity). Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding (By similarity). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism (By similarity). Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (By similarity). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (PubMed:21304510).|||Endoplasmic reticulum membrane|||Golgi apparatus|||Homodimer; homodimerization is required for UFM1 activation (By similarity). Interacts (via UIS motif) with UFM1; binds UFM1 via a trans-binding mechanism in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (PubMed:21304510). Interacts (via UIS motif) with GABARAPL2 and, with lower affinity, with GABARAP and GABARAPL1 (By similarity). Interacts (via C-terminus) with UFC1 (By similarity).|||Nucleus|||The UFM1-interacting sequence (UIS) motif mediates interaction with both UFM1 and LC3/GABARAP proteins (GABARAP, GABARAPL1 and GABARAPL2).|||Was initially reported to mediate activation of SUMO2 in addition to UFM1 (By similarity). However, it was later shown that it is specific for UFM1 (PubMed:21304510). http://togogenome.org/gene/10090:Hmmr ^@ http://purl.uniprot.org/uniprot/Q00547 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell surface|||Cytoplasm|||Interacts with ANKRD26 (By similarity). Interacts with DYNLL1 (By similarity). Interacts with FAM83D/CHICA (By similarity).|||Receptor for hyaluronic acid (HA) (PubMed:1376732). Involved in cell motility (PubMed:1376732). When hyaluronan binds to HMMR, the phosphorylation of a number of proteins, including the PTK2/FAK1 occurs. May also be involved in cellular transformation and metastasis formation, and in regulating extracellular-regulated kinase (ERK) activity. May act as a regulator of adipogenesis (PubMed:22666460).|||Ubiquitously expressed.|||spindle http://togogenome.org/gene/10090:Rnf166 ^@ http://purl.uniprot.org/uniprot/Q3U9F6 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||E3 ubiquitin-protein ligase that promotes the ubiquitination of different substrates. In turn, participates in different biological processes including interferon production or autophagy. Plays a role in the activation of RNA virus-induced interferon-beta production by promoting the ubiquitination of TRAF3 and TRAF6. Also plays a role in the early recruitment of autophagy adapters to bacteria. Mediates 'Lys-29' and 'Lys-33'-linked ubiquitination of SQSTM1 leading to xenophagic targeting of bacteria and inhibition of their replication. http://togogenome.org/gene/10090:Plekhd1 ^@ http://purl.uniprot.org/uniprot/B2RPU2 ^@ Similarity ^@ Belongs to the PLEKHD1 family. http://togogenome.org/gene/10090:Sptbn4 ^@ http://purl.uniprot.org/uniprot/E9PX29|||http://purl.uniprot.org/uniprot/Q8VIE5 ^@ Similarity ^@ Belongs to the spectrin family. http://togogenome.org/gene/10090:Szt2 ^@ http://purl.uniprot.org/uniprot/A2A9C3 ^@ Disruption Phenotype|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids (By similarity). In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose (PubMed:28199306, PubMed:28199315). May play a role in the cellular response to oxidative stress (PubMed:20045724).|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Induced in cells resistant to glutamate toxicity.|||Knockout mice lacking Szt2 are born at an expected Mendelian ratio, but they do not survive weaning or any fasting (PubMed:28199315). They display increased mTORC1 signaling in several tissues (PubMed:28199306, PubMed:28199315). Mutant mice with a gene trap-induced truncating mutation display embryonic lethality and surviving mutants show significantly decreased threshold to minimal forebrain clonic seizures (PubMed:19624305).|||Lysosome membrane|||Mostly expressed in brain, spinal cord and lung.|||Part of the KICSTOR complex composed of KPTN, ITFG2, KICS2 and SZT2. SZT2 probably serves as a link between the other three proteins in the KICSTOR complex and may mediate the direct interaction with the GATOR complex via GATOR1. The KICSTOR complex interacts directly with the GATOR1 complex and most probably indirectly with the GATOR2 complex in an amino acid-independent manner.|||Peroxisome http://togogenome.org/gene/10090:Or5p51 ^@ http://purl.uniprot.org/uniprot/Q8VF65 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Otof ^@ http://purl.uniprot.org/uniprot/Q9ESF1 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the ferlin family.|||Binds Ca(2+). The ions are bound to the C2 1 domain.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in the organ of Corti in the inner hair cells (IHCs), but not in the outer hair cells (OHCs) at 16 dpc. Expressed strongly in the IHCs and faintly in the OHCs at 18 dpc (at protein level).|||Golgi apparatus membrane|||Interacts with SNAP25; the interaction is direct. Interacts with STX1; the interaction is direct. Interacts with RAB8B.|||Isoform 1 is expressed in cochlea and brain. Expressed in the cochlear and vestibular hair cells. Expressed in both inner and outer hair cells (IHCs and OHCs) and cochlear ganglions neurons at postnatal day 2 (P2) and 6 (P6). Expressed only in IHCs at postnatal day 60 (P60) (at protein level). Strongly expressed in brain and inner ear. In the inner ear, it is mainly expressed in the cochlear IHC and vestibular type I sensory hair cells. Weakly expressed in eye, heart, skeletal muscle, liver, kidney, lung and testis.|||Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes.|||Mice lacking Otof display hearing loss (PubMed:17055430, PubMed:17329413). Both outer hair cells (OHCs) and the afferent auditory pathway are functional (PubMed:17055430). Despite normal inner hair cells (IHCs) and ribbon synapse ultrastructures, these mice exhibit an almost complete abolition of IHC synaptic exocytosis in response to cell depolarization (PubMed:17055430).|||Presynaptic cell membrane|||The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding (By similarity).|||synaptic vesicle membrane http://togogenome.org/gene/10090:Pclaf ^@ http://purl.uniprot.org/uniprot/Q9CQX4 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts (when monoubiquitinated at Lys-15 and Lys-24) with PCNA. Interacts with isoform 2/p33ING1b of ING1. Interacts with BRCA1 (By similarity).|||Monoubiquitinated at Lys-15 and Lys-24 during normal S phase, promoting its association with PCNA. Also diubiquitinated at these 2 sites. Following DNA damage, monoubiquitin chains at Lys-15 and Lys-24 are probably extended, leading to disrupt the interaction with PCNA. Polyubiquitinated by the APC/C complex at the mitotic exit, leading to its degradation by the proteasome (By similarity).|||Nucleus|||PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with PCNA is disrupted, facilitating the interaction between monoubiquitinated PCNA and the translesion DNA synthesis DNA polymerase eta (POLH) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number (By similarity).|||The D-box (destruction box) mediates the interaction with APC/C proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.|||The KEN box is required for the association with the APC/C complex.|||The PIP-box mediates the interaction with PCNA.|||The initiation motif is required for efficient chain initiation by the APC/C complex E2 ligase UBE2C. It determines the rate of substrate's degradation without affecting its affinity for the APC/C, a mechanism used by the APC/C to control the timing of substrate proteolysis during the cell cycle (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Pcdhga10 ^@ http://purl.uniprot.org/uniprot/Q91XY9 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Spaca1 ^@ http://purl.uniprot.org/uniprot/Q9DA48 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in testis from 3 weeks of age onwards.|||Males are sterile, while female fertility is not affected. Spermatozoa have significantly impaired swimming ability. The sperm head has a rounded shape instead of the normal hook-shaped morphology. The acrosome membrane does not associate normally with the nuclear envelope or intermediate filament bundles, and fails to expand along the nuclear surface. The sperm nucleus remains globular and mitochondria appear disorganized.|||N-glycosylated.|||Plays a role in acrosome expansion and establishment of normal sperm morphology during spermatogenesis. Important for male fertility.|||Testis specific (at protein level).|||acrosome inner membrane http://togogenome.org/gene/10090:Smagp ^@ http://purl.uniprot.org/uniprot/A0A2R8W734|||http://purl.uniprot.org/uniprot/Q99KC7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SMAGP family.|||Cell membrane|||Cytoplasmic vesicle membrane|||May play a role in epithelial cell-cell contacts. May play a role in tumor invasiveness and metastasis formation (By similarity).|||Membrane|||O-glycosylated. The O-glycan is modified with sialic acid residues (By similarity). http://togogenome.org/gene/10090:Gata3 ^@ http://purl.uniprot.org/uniprot/P23772|||http://purl.uniprot.org/uniprot/Q3U0R5 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA via the 2 GATA-type zinc fingers. Each zinc finger may bind either adjacent sites in a palindromic motif, or a different DNA molecule allowing looping and long-range gene regulation (By similarity).|||Interacts with TBX21 ('Tyr-525' phosphorylated form).|||Nucleus|||T-cell specific.|||The YxKxHxxxRP motif is critical for DNA-binding and function.|||Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation process following immune and inflammatory responses. Positively regulates ASB2 expression (PubMed:31175139). Coordinates macrophage transcriptional activation and UCP2-dependent metabolic reprogramming in response to IL33. Upon tissue injury, acts downstream of IL33 signaling to drive differentiation of inflammation-resolving alternatively activated macrophages.|||Up-regulated during macrophage differentiation in response to IL33. http://togogenome.org/gene/10090:Adrb3 ^@ http://purl.uniprot.org/uniprot/P25962|||http://purl.uniprot.org/uniprot/Q3UP63 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB3 sub-subfamily.|||Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.|||Cell membrane|||Interacts with ARRDC3.|||Membrane|||White and brown adipose tissues, and digestive tract. Isoform B highest in brain. http://togogenome.org/gene/10090:Efnb2 ^@ http://purl.uniprot.org/uniprot/P52800|||http://purl.uniprot.org/uniprot/Q4FJM3 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Cell membrane|||Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.|||Expressed in inner and outer pillar cells of the organ of Corti (at protein level) (PubMed:30639848). Expressed on lateral floor plate cells, specifically on commissural axon segments that have passed through the floor plate. Expressed in cells of the retinal ganglion cell layer during retinal axon guidance to the optic disk (PubMed:7651410, PubMed:10704386). Expressed in myogenic progenitor cells (PubMed:27446912).|||Expressed in the floor plate throughout the period of commissural axon pathfinding (PubMed:7651410, PubMed:10704386). In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912).|||Inducible phosphorylation of tyrosine residues in the cytoplasmic domain.|||Interacts with PDZRN3. Binds to the ephrin receptor EPHA3, EPHA4 and EPHB4 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||adherens junction http://togogenome.org/gene/10090:Wasl ^@ http://purl.uniprot.org/uniprot/Q3TXX8|||http://purl.uniprot.org/uniprot/Q91YD9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds actin and the Arp2/3 complex. Interacts with CDC42 (By similarity). Interacts with FCHSD1 (PubMed:29887380). Interacts with FCHSD2 (PubMed:23437151, PubMed:29887380). Binds to SH3 domains of GRB2. Interacts with the C-terminal SH3 domain of DNMBP (PubMed:14506234). Interacts with SNX9 (By similarity). Interacts with the WW domains of PRPF40A/FBP11 (PubMed:14697212). Interacts with PTK2/FAK1 (PubMed:14676198). Interacts with PACSIN1, PACSIN2 and PACSIN3 (PubMed:11082044). Interacts with NOSTRIN. Binds to TNK2. Interacts with SNX33. Interacts with NONO (via second RRM domain); the interaction is direct. Component of a multiprotein complex with NONO and SFPQ; associates with the complex via direct interaction with NONO (By similarity).|||Cytoplasm|||Nucleus|||Phosphorylation at Ser-239, Tyr-253, Ser-480 and Ser-481 enhances actin polymerization activity.|||Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. Involved in various processes, such as mitosis and cytokinesis, via its role in the regulation of actin polymerization. Together with CDC42, involved in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. In addition to its role in the cytoplasm, also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization (By similarity). Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression (PubMed:12871950). Plays a role in dendrite spine morphogenesis (PubMed:25851601).|||cytoskeleton http://togogenome.org/gene/10090:Hdac5 ^@ http://purl.uniprot.org/uniprot/B7ZDF5|||http://purl.uniprot.org/uniprot/B7ZDF7|||http://purl.uniprot.org/uniprot/Q3UJF1|||http://purl.uniprot.org/uniprot/Q6P9T4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the histone deacetylase family. HD type 2 subfamily.|||Nucleus|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. http://togogenome.org/gene/10090:Sytl4 ^@ http://purl.uniprot.org/uniprot/Q9R0Q1 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in the pancreatic islet, in particular in insulin-positive beta cells, and in pituitary.|||May be due to an intron retention.|||Membrane|||Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner.|||Part of a ternary complex containing STX1A and RAB27A. Can bind both dominant negative and dominant active mutants of RAB27A. Binds STXBP1, RAB3A, RAB8A and RAB27B. Interacts with MYO5A.|||secretory vesicle membrane http://togogenome.org/gene/10090:Arl13b ^@ http://purl.uniprot.org/uniprot/Q640N2|||http://purl.uniprot.org/uniprot/Q9CUD0 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Arf family.|||Cilium-specific protein required to control the microtubule-based, ciliary axoneme structure. May act by maintaining the association between IFT subcomplexes A and B. Binds GTP but is not able to hydrolyze it; the GTPase activity remains unclear. Required to pattern the neural tube. Involved in cerebral cortex development: required for the initial formation of a polarized radial glial scaffold, the first step in the construction of the cerebral cortex, by regulating ciliary signaling (PubMed:23817546). Regulates the migration and placement of postmitotic interneurons in the developing cerebral cortex (PubMed:23153492).|||Cilium-specific protein. Expressed in neuroepithelial cells and developing radial glia of the developing cerebral cortex: present in both neuroepithelial and radial progenitor cells. In radial progenitors, found in the apical, cell soma domains of these cells (at protein level). Expressed in the primary cilia of postmitotic cortical neurons during embryonic and postnatal development.|||Impaired cilium's ability to convey critical extracellular signals such as Shh, without destroying cilia and their downstream pathways. Mice show a constitutive low-level of Shh activity owing to loss of modulation of Gli2 activator, corresponding to the specification of progenitors of motoneurons through most of the neural tube. In contrast to other mouse mutants that disrupt cilia, Gli3 repressor activity is unaffected in mutants (PubMed:17488627). Mutants show abnormal cilia in which components of Shh signaling are not regulated properly: Ptch1 and Smo localize to cilia regardless of Shh stimulation, and there is no Gli enrichment in cilia upon Shh stimulation (PubMed:21976698). Conditional deletion disrupts interneuronal placement, but not postmigratory differentiation in the developing cerebral cortex (PubMed:23153492). Early neuroepithelial-specific deletion in cortical progenitors induces a reversal of the apical-basal polarity of radial progenitors and aberrant neuronal placement (PubMed:23817546).|||Monomer. Interacts with IFT complex B components IFT46 and IFT74 (By similarity). Interacts with CIMAP3 (By similarity) (PubMed:20643351). Interacts with EXOC2; regulates ARL13B localization to the cilium membrane (PubMed:26582389).|||Sumoylation is required for PKD2 entry into cilium.|||Used as a ciliary marker because of its specific localization to microtubule doublets of the ciliary axoneme. Frequently used to study cilium signaling, since in contrast to most cilia null mutants, deletion of Arl13b impairs without destroying cilia and their downstream pathways (PubMed:23817546).|||cilium|||cilium membrane http://togogenome.org/gene/10090:Snrpd3 ^@ http://purl.uniprot.org/uniprot/P62320 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP core protein family.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (By similarity). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:19470752). Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts (via C-terminus) with SMN1 (via Tudor domain); the interaction is direct (By similarity).|||Methylated on arginine residues by PRMT5 and PRMT7; probable asymmetric dimethylation which is required for assembly and biogenesis of snRNPs.|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (PubMed:19470752).|||cytosol http://togogenome.org/gene/10090:Tcp11l1 ^@ http://purl.uniprot.org/uniprot/Q8BTG3 ^@ Similarity ^@ Belongs to the TCP11 family. http://togogenome.org/gene/10090:Sprn ^@ http://purl.uniprot.org/uniprot/Q8BWU1 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Appears at embryonic day 16 and persists in early postnatal life and in the brains of adults (at protein level).|||Belongs to the SPRN family.|||Cell membrane|||Mainly expressed in brain (at protein level). In brain, it is highly expressed in the hippocampus and cerebellum and is also expressed at lower level in other areas of the brain including the cerebral cortex, the thalamus and the medulla. In hippocampus and cerebellum it is highly expressed in the cell bodies of pyramidal cells and Purkinje cells, respectively.|||N-glycosylated.|||Prion-like protein that has PrP(C)-like neuroprotective activity. May act as a modulator for the biological actions of normal and abnormal PrP.|||Strongly down-regulated in prion-infected brains (at protein level).|||This protein is a candidate for 'Pi' factor, a PrP(C)-like protein able to compensate for the absence of PrPC in mice lacking Prnp. http://togogenome.org/gene/10090:Cyp3a13 ^@ http://purl.uniprot.org/uniprot/Q3UW87|||http://purl.uniprot.org/uniprot/Q64464 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Can activate aflatoxin B1 to a genotoxic product.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Gys1 ^@ http://purl.uniprot.org/uniprot/Q9Z1E4 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Allosteric activation by glucose-6-phosphate. Phosphorylation reduces the activity towards UDP-glucose. When in the non-phosphorylated state, glycogen synthase does not require glucose-6-phosphate as an allosteric activator; when phosphorylated it does (By similarity).|||Belongs to the glycosyltransferase 3 family.|||Interacts with GYG1.|||Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CSNK2A2 is required for inhibitory phosphorylation at Ser-641 (site 3a), Ser-645 (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A an GSK3B. Phosphorylated at Ser-641 by PASK, leading to inactivation; phosphorylation by PASK is inhibited by glycogen. Phosphorylated at Ser-641 by DYRK2, leading to inactivation. Dephosphorylation at Ser-641 and Ser-645 by PP1 activates the enzyme (By similarity). Phosphorylation at Ser-8 by AMPK inactivates the enzyme activity.|||Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan. http://togogenome.org/gene/10090:Cfap100 ^@ http://purl.uniprot.org/uniprot/Q80VN0 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CFAP100 family.|||Intron retention, and aberrant splicing.|||Intron retention.|||May play a role in ciliary/flagellar motility by regulating the assembly and the activity of axonemal inner dynein arm.|||cilium axoneme http://togogenome.org/gene/10090:Rps6kc1 ^@ http://purl.uniprot.org/uniprot/Q8BLK9 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. S6 kinase subfamily.|||Cytoplasm|||Due to a partial intron retention.|||Early endosome|||Interacts with SPHK1 and phosphatidylinositol 3-phosphate. Interacts (via PX domain) with PRDX3.|||May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell. Plays a role in the recruitment of PRDX3 to early endosomes.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane|||The PX domain is essential for its localization to the early endosomes.|||The first protein kinase domain appears to be a pseudokinase domain as it does not contain the classical characteristics, such as the ATP-binding motif, ATP-binding site and active site. http://togogenome.org/gene/10090:Srsf6 ^@ http://purl.uniprot.org/uniprot/Q3TWW8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Binds SREK1/SFRS12. Interacts with DYRK1A (By similarity).|||Extensively phosphorylated on serine residues in the RS domain. Phosphorylated by DYRK1A, probably in the RS domain. Phosphorylation by DYRK1A modulates alternative splice site selection and inhibits the expression of MAPT/Tau exon 10 (By similarity).|||Nucleus|||Nucleus speckle|||Plays a role in constitutive splicing and modulates the selection of alternative splice sites. Plays a role in the alternative splicing of MAPT/Tau exon 10. Binds to alternative exons of TNC pre-mRNA and promotes the expression of alternatively spliced TNC. Plays a role in wound healing and in the regulation of keratinocyte differentiation and proliferation via its role in alternative splicing (By similarity). http://togogenome.org/gene/10090:Akr1b10 ^@ http://purl.uniprot.org/uniprot/G5E895|||http://purl.uniprot.org/uniprot/Q8BIV6 ^@ Similarity ^@ Belongs to the aldo/keto reductase family. http://togogenome.org/gene/10090:Aimp2 ^@ http://purl.uniprot.org/uniprot/Q8R010|||http://purl.uniprot.org/uniprot/Q8R3V2 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:12060739). Interacts (via N-terminus) with KARS1. Interacts with EPRS1. Forms a linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit complex. Binds FUBP1 (via C-terminus) (By similarity). Interacts in both its unphosphorylated and phosphorylated forms with p53/TP53 (via N-terminus) in the nucleus following UV irradiation. Interacts (via N-terminus) with PRKN/parkin (via first RING-type domain). Interacts with TARS3.|||Phosphorylated on serine residues in response to UV irradiation.|||Reduced levels of component enzymes and associated factors of the aminoacyl-tRNA synthase complex, lack of complex formation and lethality within two days of birth. Neonates display severe hyperplasia in a number of organs including lung, intestine and liver, lung failure, and disturbed thymocyte proliferation and differentiation. Embryonic fibroblasts deficient in Aimp2 are resistant to apoptosis following UV irradiation.|||Required for assembly and stability of the aminoacyl-tRNA synthase complex (PubMed:12060739). Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation (PubMed:12819782). Blocks MDM2-mediated ubiquitination and degradation of p53/TP53 (PubMed:18695251). Functions as a proapoptotic factor (PubMed:16135753).|||Ubiquitinated by PRKN, leading to its degradation by the proteasome.|||cytosol http://togogenome.org/gene/10090:Pask ^@ http://purl.uniprot.org/uniprot/Q8CEE6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylated on Thr-1221 and Thr-1225. Autophosphorylation is activated by phospholipids (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||No visible phenotype under normal conditions: mice show normal development, growth and reproduction. Fertility and sperm production and motility are not affected in males. Under high-fat diet, mice seem to be protected from deleterious effects, including obesity, liver triglyceride accumulation and insulin resistance (PubMed:17878307). In contrast, the lean phenotype appears only after feeding a high-fat diet: under normal chow diet, body weight, fat composition, oxygen consumption are not distinguishable from wild-type mice (PubMed:17192472). The only difference between these 2 experiments is that mice were backcrossed into C57BL/6 5 times in the first study (PubMed:17878307), while the 10th backcross was used in the second study (PubMed:17192472). Female but not male mice show an increased ventilatory response to acute hypoxia and fail to reach ventilatory acclimatization to chronic hypoxia.|||Nucleus|||Protein kinase activity is inhibited by the first PAS domain: binding of an unidentified ligand desinhibits the protein kinase activity. May be activated by autophosphorylation on Thr-1221 and Thr-1225. Autophosphorylation is enhanced upon phosphatidylinositol monophosphate (phosphatidylinositol 4-phosphate) binding and inhibited upon phosphatidylinositol bi- and tri-phosphate binding. In contrast, phosphorylation of target proteins is inhibited upon all phosphatidylinositol-binding (phosphatidylinositol mono- bi- and tri-phosphate) (By similarity).|||Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation.|||The protein kinase domain mediates binding to phosphatidylinositol.|||Ubiquitously expressed. Strongly up-regulated in postmeiotic germ cells during spermatogenesis. http://togogenome.org/gene/10090:Nrn1l ^@ http://purl.uniprot.org/uniprot/Q8C4W3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the neuritin family.|||Cell membrane http://togogenome.org/gene/10090:Hacd4 ^@ http://purl.uniprot.org/uniprot/A2AKM2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the very long-chain fatty acids dehydratase HACD family.|||Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.|||Endoplasmic reticulum membrane|||May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex.|||Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity. http://togogenome.org/gene/10090:Inpp5a ^@ http://purl.uniprot.org/uniprot/Q7TNC9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type I family.|||Cell membrane|||Expressed at high levels in cerebellar Purkinje cells (at protein level) (PubMed:26051944). Expressed in Sertoli cells of the testis (PubMed:31112734).|||Genetic deletion causes a perinatal lethal phenotype in most mutant mice (PubMed:26051944). A small percentage of mutants thrive and have a phenotype characterized by an ataxic gait and progressive Purkinje cell degeneration (PubMed:26051944). Purkinje cell death is spatially patterned with surviving Purkinje cells appearing normal and maintaining molecular layer morphology (PubMed:26051944). Phosphatase activity toward phosphoinositol substrates is reduced in the mutant relative to wild-type littermates (PubMed:26051944).|||Interacts with TASOR.|||Isoprenylation at Cys-409 is required for localization at the membrane.|||Phosphatase that specifically hydrolyzes the 5-phosphate of inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, and inositol 1,3,4,5-tetrasphosphate to inositol 1,3,4-trisphosphate (PubMed:26051944). Plays a crucial role in the survival of cerebellar Purkinje cells (PubMed:26051944).|||dendrite http://togogenome.org/gene/10090:Myh11 ^@ http://purl.uniprot.org/uniprot/A0A2R8VHF9|||http://purl.uniprot.org/uniprot/E9QPE7 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Serpine3 ^@ http://purl.uniprot.org/uniprot/E9Q6A2 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Fads3 ^@ http://purl.uniprot.org/uniprot/Q3T9H9|||http://purl.uniprot.org/uniprot/Q9JJE7 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family.|||Endoplasmic reticulum membrane|||Highly expressed in liver and kidney (at protein level).|||Mammals have different sphingoid bases that differ in their length and/or pattern of desaturation and hydroxyl groups. The predominant sphingoid base that comprises mammalian ceramides is sphing-4-enine (sphingosine or SPH) which has a trans (E) desaturation at carbon 4. FADS3 is a desaturase that introduces a cis (Z) double bond between carbon 14 and carbon 15 of the sphingoid base (also known as long chain base, LCB), producing LCBs such as sphinga-4,14-dienine (SPD, d18:2(4E,14Z)) from SPH. Prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates. Capable of metabolizing also the SPH in its free form. SPD ceramides occur widely in mammalian tissues and cells. Due to their unusual structure containing a cis double bond, SPD ceramides may have an opposite, negative role in lipid microdomain formation relative to conventional ceramides. Could be involved in the detoxification of 1-deoxy sphingolipids, by desaturating the cytotoxic 1-deoxysphinganine (1-deoxySA, m18:0), produced under pathological conditions, to 1-deoxysphingenine (1-deoxysphingosine, 1-deoxySO, m18:1). Although prefers SPH-containing ceramides (N-acylsphing-4-enines) as substrates, it also exhibits activity toward dihydrosphingosine-containing CERs (N-acylsphinganines) and produces 14Z-SPH-containing sphingolipids. Its desaturase mechanism involves an electron transfer facilitated by cytochrome b5 (By similarity). FADS3 also acts as a methyl-end fatty acyl coenzyme A (CoA) desaturase that introduces a cis double bond between the preexisting double bond and the terminal methyl group of the fatty acyl chain. Desaturates (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 13 to generate (11E,13Z)-octadecadienoate (also known as conjugated linoleic acid 11E,13Z-CLA) (By similarity).|||The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases.|||Two potential isoforms are detected in various tissues. A 75 kDa isoform is expressed in lung. A 37 kDa isoform is expressed in lung, liver and kidney. http://togogenome.org/gene/10090:Cd99l2 ^@ http://purl.uniprot.org/uniprot/Q8BIF0 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 12.5 dpc, expressed in most tissues, especially in the nervous system, including the cerebral cortex, cerebellum, spinal cord and ganglion. There is no change in expression pattern from 12.5 dpc to neonatal day 1. Highly expressed in the subventricular zone and cortical plate of fetal brain and in the dorsal root ganglion of the peripheral nervous system. Except in the nervous system, expression in adult tissues is weaker than in fetal ones.|||Belongs to the CD99 family.|||Cell junction|||Cell membrane|||Highly expressed in the nervous system, including brain, dentate nucleus of hippocampus, granular and Purkinje cells of cerebellum, brain stem nucleus and choroid plexus. Expressed in peripheral blood T- and B-cells and neutrophils (at protein level). Almost undetectable in bone marrow-derived neutrophils (at protein level). Also expressed in thymocytes (at protein level) with higher expression in cortical thymocytes than in medullary thymocytes. Expressed at high levels in testis (mostly in germ cells and Sertoli cells) and ovary (mostly in granulosa cells). Expressed in lung, heart, kidney and liver (at protein level); however, expression in heart, kidney and liver seems restricted to endothelial cells (at protein level). Highly expressed in endothelial cells and to a lower level in vascular smooth muscle cells (at protein level). Low expression in spleen.|||O-glycosylated.|||Plays a role in a late step of leukocyte extravasation helping cells to overcome the endothelial basement membrane. Acts at the same site as, but independently of, PECAM1. Homophilic adhesion molecule, but these interactions may not be required for cell aggregation.|||Secreted|||Seems to be the major transcript. http://togogenome.org/gene/10090:Porcn ^@ http://purl.uniprot.org/uniprot/Q9JJJ7 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the membrane-bound acyltransferase family. Porcupine subfamily.|||Endoplasmic reticulum membrane|||Expressed in brain, heart, kidney, liver, lung, muscle, spleen and testis. Isoform 4 is strongly expressed in kidney, liver, lung, spleen and testis. Isoform 1 is strongly expressed in brain, heart and muscle and poorly in kidney, liver, lung, spleen and testis.|||Interacts with WNT1, WNT3, WNT3A, WNT4, WNT5A, WNT5B, WNT6, WNT7A and WNT7B.|||Isoform 1, isoform 2, isoform 3 and isoform 4 are expressed at different levels in embryo at 9.5, 10.5, 11.5, 12.5, 13.5 and 15.5 dpc.|||Protein-serine O-palmitoleoyltransferase that acts as a key regulator of the Wnt signaling pathway by mediating the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors.|||Was initially thought to mediate palmitoylation of Wnt proteins. It was later shown that instead it acts as a serine O-palmitoleoyltransferase that mediates the attachment of palmitoleate, a 16-carbon monounsaturated fatty acid (C16:1(9Z)), to Wnt proteins (PubMed:17141155, PubMed:24798332). http://togogenome.org/gene/10090:Gm1140 ^@ http://purl.uniprot.org/uniprot/A2BH01 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Cpeb2 ^@ http://purl.uniprot.org/uniprot/A0A0H2UH22|||http://purl.uniprot.org/uniprot/E9Q5X2 ^@ Similarity ^@ Belongs to the RRM CPEB family. http://togogenome.org/gene/10090:H4c6 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Grk4 ^@ http://purl.uniprot.org/uniprot/O70291 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.|||Cytoplasm|||Inhibited by heparin.|||Interacts with DRD3.|||Palmitoylated.|||Specifically phosphorylates the activated forms of G protein-coupled receptors.|||cell cortex http://togogenome.org/gene/10090:Mpzl3 ^@ http://purl.uniprot.org/uniprot/Q3V3F6 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the myelin P0 protein family.|||Defects in Mpzl3 are the cause of rough coat (rc) phenotype, an autosomal-recessive mutation, arose spontaneously in C57BL/6J mice. Rc mice develop severe skin and hair abnormalities, including cyclic and progressive hair loss and sebaceous gland hypertrophy.|||Mediates homophilic cell-cell adhesion.|||Membrane|||Present in all tissues tested, including the skin. Present in the keratinocytes and sebocytes in the skin (at protein level). http://togogenome.org/gene/10090:Vac14 ^@ http://purl.uniprot.org/uniprot/Q80WQ2 ^@ Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VAC14 family.|||Defects in Vac14 are the cause of the infantile gliosis phenotype (ingls). Mice exhibit reduced body size and diluted pigmentation that can be recognized as early as postnatal day 3 (P3). By P14, the mice exhibit a tremor and impaired motor function. Maximal survival of the mice is for 3 weeks. Small areas with the appearance of spongiform degeneration are visible in several brain regions, including the thalamus, brain stem and cerebellar nucleus.|||Endosome membrane|||Forms pentamers. Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities. Interacts with NOS1.|||Mice die perinatally and exhibit profound degeneration in certain regions of the central and peripheral nervous systems. Selected regions in the brain are affected, especially the medulla, the pons and the midbrain and increased cell death occurs in these areas. Affected neurons contain large vacuoles.|||Microsome membrane|||Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes into a star-shaped structure and nucleates the assembly of the complex. The pentamer binds a single copy each of PIKFYVE and FIG4 and coordinates both PIKfyve kinase activity and FIG4 phosphatase activity, being required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.|||The C-terminal domain (residues 523-782) mediates pentameric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex.|||Ubiquitous. http://togogenome.org/gene/10090:Cfap300 ^@ http://purl.uniprot.org/uniprot/Q8CC70 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CFAP300 family.|||Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. May play a role in outer and inner dynein arm assembly.|||Cytoplasm|||Expressed in the left-right organiser (LRO) node at 8.25 dpc.|||Interacts with DNAAF2.|||cilium axoneme http://togogenome.org/gene/10090:Ldha ^@ http://purl.uniprot.org/uniprot/A0A1B0GSX0|||http://purl.uniprot.org/uniprot/P06151|||http://purl.uniprot.org/uniprot/Q564E2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LDH/MDH superfamily. LDH family.|||Cytoplasm|||Homotetramer. Interacts with PTEN upstream reading frame protein MP31.|||ISGylated.|||Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). http://togogenome.org/gene/10090:Wdr70 ^@ http://purl.uniprot.org/uniprot/Q3TWF6 ^@ Similarity ^@ Belongs to the WD repeat GAD-1 family. http://togogenome.org/gene/10090:Fam183b ^@ http://purl.uniprot.org/uniprot/A0A0R4J0N6|||http://purl.uniprot.org/uniprot/D2D553|||http://purl.uniprot.org/uniprot/Q5NC57 ^@ Developmental Stage|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CFAP144 family.|||Expressed in the developing fetal lung epithelium and embryonic ventral node (at protein level).|||Expression is activated by FOXJ1 and NOTO.|||Predominantly expressed in tissues containing motile cilia.|||cilium basal body http://togogenome.org/gene/10090:Osbpl9 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXH3|||http://purl.uniprot.org/uniprot/A2A8Z1|||http://purl.uniprot.org/uniprot/E9PXZ2|||http://purl.uniprot.org/uniprot/Q5FWX7|||http://purl.uniprot.org/uniprot/Q8R0G3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OSBP family.|||Heterodimer with OSBPL11. Interacts with OSBPL10.|||Late endosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Kank2 ^@ http://purl.uniprot.org/uniprot/Q8BX02 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts (non-phosphorylated form) with NCOA1; NCOA2 AND NCOA3 (By similarity). Interacts with AIFM1 (By similarity). Interacts with ARHGDIA; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (By similarity). Interacts (via ANK repeats 1-5) with KIF21A (via residues 1148-1169) (By similarity).|||Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3 (By similarity). Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria (By similarity). Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis (By similarity). Involved in the negative control of vitamin D receptor signaling pathway (By similarity). Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway (PubMed:25961457). May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney (PubMed:25961457). Through the Rho signaling pathway may also regulate cell proliferation (PubMed:16024821).|||Mitochondrion|||Phosphorylated by casein kinase II upon estrogen stimulation (By similarity). Phosphorylation induces the release by KANK2 of NCOA1 and its translocation to the nucleus where NCOA1 can activate gene transcription (By similarity).|||Widely expressed with highest levels in liver and skeletal muscle. http://togogenome.org/gene/10090:Epg5 ^@ http://purl.uniprot.org/uniprot/Q80TA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EPG5 family.|||Interacts with RAN.|||Involved in autophagy. May play a role in a late step of autophagy, such as clearance of autophagosomal cargo. Plays a key role in innate and adaptive immune response triggered by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides from pathogens, and mediated by the nucleotide-sensing receptor TLR9. It is necessary for the translocation of CpG dinucleotides from early endosomes to late endosomes and lysosomes, where TLR9 is located.|||Lysosome|||perinuclear region http://togogenome.org/gene/10090:Slc35a4 ^@ http://purl.uniprot.org/uniprot/Q9D321 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.|||Found in a complex with SLC35A2 and SLC35A3.|||Golgi apparatus membrane|||Mediates the transport of CDP-ribitol (By similarity). Does not exhibit CMP-sialic acid, UDP-galactose and UDP-N-acetylglucosamine transport activity (By similarity). http://togogenome.org/gene/10090:Tut7 ^@ http://purl.uniprot.org/uniprot/E9PUA2|||http://purl.uniprot.org/uniprot/Q5BLK4 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DNA polymerase type-B-like family.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Double conditional knockouts that have deleted both TUT4 and TUT7 at the secondary oocyte stage are infertile. Females ovulate normal numbers of oocytes with normal morphology of antral follicles but with a slight decrease in the frequency of surrounded nucleolus state oocytes. Mutant oocytes are unable to support early embryonic development, they fail to complete meiosis I properly.|||Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:28792939). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (PubMed:28792939). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of miRNA precursors, including that of let-7 (pre-let-7) (PubMed:22898984). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A. Due to functional redundancy between ZCCHC6 and ZCCHC11, the identification of the specific role of each of these proteins is difficult (By similarity) (PubMed:22898984). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (By similarity). Also functions as an integral regulator of microRNA biogenesiS using 3 different uridylation mechanisms (By similarity). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 oligouridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (By similarity). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (By similarity). Does not play a role in replication-dependent histone mRNA degradation (By similarity). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:28792939, PubMed:22898984). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (By similarity).|||Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activities while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation. http://togogenome.org/gene/10090:Spsb4 ^@ http://purl.uniprot.org/uniprot/Q8R5B6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPSB family.|||Component of the probable ECS(SPSB4) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB4 (By similarity). Interacts with CUL5; RNF7; ELOB and ELOC (By similarity). Interacts with MET (PubMed:16369487). Interacts (via B30.2/SPRY domain) with PAWR; this interaction occurs in association with the Elongin BC complex (PubMed:16369487, PubMed:20561531). Interacts with NOS2 (PubMed:20603330). Interacts with EPHB2 (By similarity).|||Cytoplasm|||Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (By similarity). Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By similarity). Diminishes EphB2-dependent cell repulsive responses by mediating the ubiquitination and degradation of the EphB2/CTF2 (By similarity). Regulates cellular clock function by mediating ubiquitination and proteasomal degradation of the circadian transcriptional repressor NR1D1 (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By similarity).|||cytosol http://togogenome.org/gene/10090:Ccm2 ^@ http://purl.uniprot.org/uniprot/F7AVU1|||http://purl.uniprot.org/uniprot/Q8K2Y9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCM2 family.|||Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. May act through the stabilization of endothelial cell junctions. May also function as a scaffold protein for MAP2K3-MAP3K3 signaling. Seems to play a major role in the modulation of MAP3K3-dependent p38 activation induced by hyperosmotic shock.|||Cytoplasm|||Expressed primarily in the developing neural tube at 10.5 dpc.|||Highly expressed in heart, lower expression in kidney, lung and liver (at protein level).|||Part of a complex with MAP2K3, MAP3K3 and RAC1. Binds RAC1 directly and independently of its nucleotide-bound state. Interacts with PDCD10 (By similarity). Interacts with HEG1 and KRIT1; KRIT1 greatly facilitates the interaction with HEG1.|||The C-terminal region constitutes an independently folded domain that has structural similarity with the USH1C (harmonin) N-terminus, despite very low sequence similarity. http://togogenome.org/gene/10090:Cd209b ^@ http://purl.uniprot.org/uniprot/Q8CJ91 ^@ Caution|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in skin, spleen and lung, probably in a subset of dendritic cells. Detected in spleen extrafollicular paracortical areas including the red pulp and marginal zones, and at lower levels, in the follicular area. Detected in skin suprabasal areas adjacent to the epidermis and in epidermal cell layer.|||In mouse, 5 genes homologous to human CD209/DC-SIGN and CD209L/DC-SIGNR have been identified.|||In vitro, is a receptor for HIV-1, HIV-2 and SIV, but does not transmit virus to permissive T-cells under the conditions tested.|||Membrane|||Probable pathogen-recognition receptor. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. May recognize in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens. Is a receptor for ICAM3, probably by binding to mannose-like carbohydrates. http://togogenome.org/gene/10090:Gpr141b ^@ http://purl.uniprot.org/uniprot/B9EKH0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Eif2b2 ^@ http://purl.uniprot.org/uniprot/Q99LD9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the eIF-2B alpha/beta/delta subunits family.|||Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.|||Complex of five different subunits; alpha, beta, gamma, delta and epsilon. http://togogenome.org/gene/10090:Taf7 ^@ http://purl.uniprot.org/uniprot/Q9R1C0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF7 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts with TAF1; the interaction is direct (By similarity). Interacts with TAF1, TAF5, TAF11, TAF12, and TAF13, but not with TAF10 or TBP (PubMed:10438527). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with CIITA and TAF1 and inhibits their acetyltransferase activity, and behaving as a repressor of CIITA- and TAF1-regulated promoters (By similarity).|||Nucleus|||Phosphorylated by CIITA. Phosphorylation at Ser-256 by TAF1 in early G1 phase disrupts binding to TAF1 (By similarity).|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. TAF7 forms a promoter DNA binding subcomplex of TFIID, together with TAF1 and TAF2. Part of a TFIID complex containing TAF10 (TFIID alpha) and a TFIID complex lacking TAF10 (TFIID beta).|||The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase.|||Ubiquitinated by TRIM26; leading to proteasomal degradation. http://togogenome.org/gene/10090:Or51i2 ^@ http://purl.uniprot.org/uniprot/Q8VGX6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defb5 ^@ http://purl.uniprot.org/uniprot/Q9EPV9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Dgcr2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1M6|||http://purl.uniprot.org/uniprot/P98154|||http://purl.uniprot.org/uniprot/Q6P5A9 ^@ Caution|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Probably plays a role in neural crest cell migration. May play a role in delivery of extracellular signals.|||Ubiquitous in various organs with low abundance. http://togogenome.org/gene/10090:Chst13 ^@ http://purl.uniprot.org/uniprot/D3Z6E3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 2 family.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Erc1 ^@ http://purl.uniprot.org/uniprot/F8VPM7|||http://purl.uniprot.org/uniprot/Q99MI1 ^@ Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Artifact. Missing internal sequence that does not correspond to an exon-intron boundary.|||Cytoplasm|||Golgi apparatus membrane|||Interacts with the GTB-bound forms of RAB6A isoform 1 and isoform 2 and with RAB6B. The interaction was strongest with RAB6B, followed by RAB6A isoform 2 and weakest with RAB6A isoform 1. Part of a complex with CHUK, IKBKB and IKBKG. Interacts with CHUK, IKBKB and IKBKG. The interaction with IKBKG is independent of CHUK and IKBKB. Interacts with NFKBIA (By similarity). Isoform 2 interacts through its C-terminus with the PDZ domains of RIMS1 and RIMS2. Interacts with ERC2/CAST1 (By similarity). Interacts with SDCCAG8.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane|||Presynaptic active zone|||Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex (By similarity). May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport.|||Widely expressed.|||centrosome http://togogenome.org/gene/10090:Mcm5 ^@ http://purl.uniprot.org/uniprot/P49718|||http://purl.uniprot.org/uniprot/Q8BQ03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Belongs to the MCM family.|||Chromosome|||Component of the MCM2-7 complex.|||Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex. Interacts with ANKRD17. Interacts with MCMBP. Interacts with TONSL; the interaction is direct.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Dnajc15 ^@ http://purl.uniprot.org/uniprot/Q78YY6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an import component of the TIM23 translocase complex. Stimulates the ATPase activity of HSPA9 (By similarity). Negative regulator of the mitochondrial respiratory chain. Prevents mitochondrial hyperpolarization state and restricts mitochondrial generation of ATP.|||Expressed at high levels in liver, heart, at moderate levels in kidney and, at very low levels, in lung (at protein level). High expression levels in testis. Highly expressed in CD8+ T-cells, but barely detectable in CD4+ T-cells (at protein level). Almost undetectable in B-cells.|||Interacts with the TIM23 complex. Directly interacts with PAM16/MAGMAS; this interaction counteracts DNAJC15-dependent stimulation of HSPA9 ATPase activity (By similarity). Associates with complex I of the mitochondrial electron transfer chain; this interaction may interfere with the formation of supercomplexes that facilitate the transfer of electrons between complexes.|||Mitochondrion inner membrane|||No visible phenotype. Mutant animals are viable. Both male and female are fertile and do not exhibit any obvious malformations or behavioral abnormalities. CD8+ T-cell mitochondria are hyperpolarized, compared to their wild-type counterparts. In fasted mutant animals, livers do not exhibit any signs of steatosis, but accumulate glycogen, possibly due to a sustained mitochondrial oxidation that leads to rapid metabolism of lipids, hence minimizing their accumulation in the liver and favoring glycogenesis. During fasting, loss of white fat is also more prominent than in wild type animals. http://togogenome.org/gene/10090:Pik3ap1 ^@ http://purl.uniprot.org/uniprot/Q9EQ32 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Constitutively phosphorylated. Phosphorylated on tyrosine residues in C-terminal region by ABL1 (By similarity). Phosphorylated on tyrosine residues within the YXXM motifs by BTK and SYK. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues, most likely within the YXXM motifs, via CD19 activation. Toll-like receptor activation induces appearance of a phosphorylated form associated with membranes.|||Cytoplasm|||Homooligomer (Probable). Interacts (phosphorylated on tyrosine residues within YXXM motifs) with PIK3R1 (via SH2 domain); required for BCR- and TLR-mediated activation of phosphoinositide 3-kinase. Interacts (via polyproline C-terminal region) with ABI1 (via SH3 domain); the interaction promotes phosphorylation of PIK3AP1 by ABL1 (By similarity). May interact with MYD88 and TIRAP.|||Mice lacking Pik3ap1 display altered B-cell maturation and impaired immune function. Pik3ap1 depletion has an opposite effect in NK cells by promoting their maturation. Mice lacking Pik3ap1 and Cd19 have severe defects in generation of immature and mature B-cells. Moreover, mice lacking Pik3ap1 display increased IL-10, Il-12 and TNF pro-inflammatory cytokine secretion upon activation of the Toll-like receptors TLR4, TLR7 and TLR9.|||Predominantly expressed in spleen (at protein level). Expressed at lower levels in thymus, liver and lung. Expressed in B-cells, macrophages and natural killer (NK) cells.|||Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL.|||The DBB domain is required for dimerization. http://togogenome.org/gene/10090:Amelx ^@ http://purl.uniprot.org/uniprot/P63277|||http://purl.uniprot.org/uniprot/Q6PCW7|||http://purl.uniprot.org/uniprot/R9W2T8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the amelogenin family.|||Expressed in ameloblasts at the periphery of mandibular molars at P1 (PubMed:12657653). At P3 also expressed at the molar incisal region (PubMed:12657653). Expressed at the terminal of Tomes' processes of ameloblasts at the incisal region at P5 (PubMed:12657653).|||Interacts with KRT5.|||Phosphorylated by FAM20C in vitro.|||Plays a role in the biomineralization of teeth. Seems to regulate the formation of crystallites during the secretory stage of tooth enamel development. Thought to play a major role in the structural organization and mineralization of developing enamel.|||Several forms are produced by C-terminal processing.|||extracellular matrix http://togogenome.org/gene/10090:Gpat2 ^@ http://purl.uniprot.org/uniprot/Q14DK4 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GPAT/DAPAT family.|||Highly expressed in pachytene spermatocytes (at protein level) (PubMed:26268560).|||Highly expressed in the testis (PubMed:26268560). Expressed at lower levels in the heart, liver, kidney, spleen and adipose cells (PubMed:17013544, PubMed:17689486). Only detected in primary spermatocytes (PubMed:22905194).|||Inhibited by N-ethylmaleimide (NEM).|||Interacts with PIWIL2 (PubMed:23611983).|||Mitochondrion outer membrane|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||Transfers an acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate producing a lysophosphatidic acid (LPA), an essential step for the triacylglycerol (TAG) and glycerophospholipids (PubMed:17013544, PubMed:17689486, PubMed:22905194). In vitro also transfers an acyl-group from acyl-ACP to the LPA producing a phosphatidic acid (PA) (PubMed:22905194). Prefers arachidonoyl-CoA as the acyl donor (PubMed:22905194). Required for primary processing step during piRNA biosynthesis (PubMed:23611983). Molecular mechanisms by which it promotes piRNA biosynthesis are unclear and do not involve its acyltransferase activity (PubMed:23611983).|||Up-regulated by retinoic acid (PubMed:26268560). http://togogenome.org/gene/10090:Smim19 ^@ http://purl.uniprot.org/uniprot/E9PUT6|||http://purl.uniprot.org/uniprot/Q80ZU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMIM19 family.|||Membrane http://togogenome.org/gene/10090:Pdzk1 ^@ http://purl.uniprot.org/uniprot/Q9JIL4 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with NHERF1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity (By similarity). Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function.|||Belongs to the NHER family.|||Cell membrane|||Disruption of the gene was not associated with abnormal growth and development or redistribution of interacting proteins. However, a modulation of expression of selective ion channels in the kidney, as well as increased serum cholesterol levels were observed.|||Expressed in kidney, liver, small intestine. brain, lung, and testis (at protein level).|||Interaction with the C-terminus of CFTR could be mediated through independent binding of PDZ 1, 3 and 4 domains.|||Interacts with PDZK1IP1 and ABCC2. Binds to the C-terminal region of SLC26A3. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain) (By similarity). Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons (By similarity). Forms a heterodimeric complex with NHERF1. Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5, SLC26A6, NHERF2 and SLC17A1. Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus). Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Interacts (via PDZ domains 1 and 3) with SLC5A8 (via PDZ-binding motif); interaction increases nicotinate transport activity of SLC5A8 (By similarity).|||Membrane|||The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1.|||The PDZ 1 domain interacts with BCR.|||The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3.|||The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1. http://togogenome.org/gene/10090:Or55b4 ^@ http://purl.uniprot.org/uniprot/E9PX47 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Abhd16b ^@ http://purl.uniprot.org/uniprot/Q80YU0 ^@ Similarity ^@ Belongs to the AB hydrolase superfamily. ABHD16 family. http://togogenome.org/gene/10090:Fez2 ^@ http://purl.uniprot.org/uniprot/A0A3Q4EGS7|||http://purl.uniprot.org/uniprot/D3Z6D5|||http://purl.uniprot.org/uniprot/Q3TN06|||http://purl.uniprot.org/uniprot/Q3U049|||http://purl.uniprot.org/uniprot/Q6TYB5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the zygin family.|||Homodimer; disulfide-linked. May form heterodimers with FEZ1. Interacts with synaptotagmin (By similarity).|||Involved in axonal outgrowth and fasciculation. http://togogenome.org/gene/10090:Gucy2c ^@ http://purl.uniprot.org/uniprot/Q3UWA6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Cell membrane|||Endoplasmic reticulum membrane|||Glycosylation at Asn-75 and/or Asn-79 is required for interaction with VIP36 while glycosylation at Asn-345 and Asn-402 modulates ligand-mediated GC-C activation.|||Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP.|||Homotrimer. Interacts via its C-terminal region with NHERF4. Interacts with the lectin chaperone VIP36.|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Samt3 ^@ http://purl.uniprot.org/uniprot/A2ARK7|||http://purl.uniprot.org/uniprot/Q9D9H1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Gskip ^@ http://purl.uniprot.org/uniprot/Q3TBR1|||http://purl.uniprot.org/uniprot/Q8BGR8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A-kinase anchoring protein for GSK3B and PKA that regulates or facilitates their kinase activity towards their targets. The ternary complex enhances Wnt-induced signaling by facilitating the GSK3B- and PKA-induced phosphorylation of beta-catenin leading to beta-catenin degradation and stabilization respectively. Upon cAMP activation, the ternary complex contributes to neuroprotection against oxidative stress-induced apoptosis by facilitating the PKA-induced phosphorylation of DML1 and PKA-induced inactivation of GSK3B. During neurite outgrowth promotes neuron proliferation; while increases beta-catenin-induced transcriptional activity through GSK3B kinase activity inhibition, reduces N-cadherin level to promote cell cycle progression (By similarity). May play a role in cleft palate formation and is required for postnatal life through modulation of the activity of GSK3B during development (PubMed:26582204).|||Belongs to the GSKIP family.|||Cytoplasm|||Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation of GSK3B leading to GSK3B inactivation; recruits DNM1L through GSK3B for PKA-mediated phosphorylation of DNM1L; promotes beta-catenin degradation through GSK3B-induced phosphorylation of beta-catenin; stabilizes beta-catenin and enhances Wnt-induced signaling through PKA-induced phosphorylation of beta-catenin. Interacts with GSK3B; induces GSK3B-mediated phosphorylation of GSKIP and inhibits GSK3B kinase activity.|||Knockout Gskip mice die at birth. At 18.5 dpc, embryos are still alive but rapidly die within 5 to 30 min after casarean section. Embryos obtained at 18.5 dpc are cyanotic, suffer from respiratory distress, and fail to initiate breathing properly.|||Nucleus|||Phosphorylated by GSK3B. http://togogenome.org/gene/10090:Pdcd11 ^@ http://purl.uniprot.org/uniprot/Q6NS46 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Essential for the generation of mature 18S rRNA, specifically necessary for cleavages at sites A0, 1 and 2 of the 47S precursor. Directly interacts with U3 snoRNA (By similarity).|||Interacts with NF-kappa-B p50/NFKB1 and NF-kappa-B p65/RELA.|||The mRNA 5'- and 3'-ends do not match to the genomic DNA.|||Ubiquitous.|||nucleolus http://togogenome.org/gene/10090:Rtn4r ^@ http://purl.uniprot.org/uniprot/Q99PI8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nogo receptor family.|||Cell membrane|||Detected in embryonic hippocampus neurons (PubMed:22325200). Detected in brain (at protein level) (PubMed:15504325, PubMed:22406547). Detected in neurons in the neocortex, in hippocampus, dorsal thalamus, cerebellum granule cell layer and the mitral cell layer in the olfactory bulb (PubMed:15647357). Detected in brain, dorsal root ganglion and heart.|||Homodimer (PubMed:29095159). Interacts with MAG (PubMed:12089450). Interacts with RTN4 (PubMed:15504325). Interacts with NGFR(PubMed:22923615). Interacts with LINGO1(PubMed:22923615). Interacts with KIAA0319L (By similarity). Interacts with OLFM1; this inhibits interaction with LINGO1 and NGFR (PubMed:22923615). Interacts with OMG (By similarity).|||Membrane raft|||Mice are born at the expected Mendelian rate, are viable and fertile (PubMed:15504325, PubMed:15647357). They display subtle changes in exploratory behavior, manifest deficits in spatial working memory performance, and show impaired ability to stay on a rotarod (PubMed:15504325, PubMed:19052207). Compared to wild-type littermates, cultured hippocampus neurons from mutant mice display an increased number of excitatory synapses (PubMed:22325200). Effects on neurite outgrowth are controversial and may depend on the mouse strain, cell type, and the experimental conditions (PubMed:15504325, PubMed:15647357, PubMed:18411262, PubMed:19367338). Cultured neurons display impaired axon growth cone collapse in response to myelin, MAG and RTN4 (PubMed:15504325). Mutant cerebellar and dorsal root ganglion neurons show no decrease of the inhibition of neurite outgrowth by myelin or RTN4 (PubMed:15647357). Mutant cerebellar neurons display decreased inhibition of neurite outgrowth mediated by MAG and by cross-linking ganglioside GT1b (in vitro) (PubMed:18411262). Likewise, mutant sensory neurons show no decrease of the inhibition of neurite outgrowth by MAG (PubMed:19367338). Mutant mice have improved functional recovery and increased regeneration of rubrospinal and raphespinal fibers after spinal cord transection. Still, there is no regeneration of corticospinal fibers (PubMed:15504325, PubMed:15647357). Mice lacking both Rtn4r and Rtn4rl2 display no visible phenotype (PubMed:19367338). Sensory neurons from mice lacking both Rtn4r and Rtn4rl2 show moderately decreased inhibition of neurite outgrowth by MAG (PubMed:19367338). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have no visible phenotype, are healthy and viable (PubMed:22406547). Mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 have normal brain size and grossly normal brain anatomy, but display disruption of medial brain structures, including an absence of the fasciola cinereum, corpus callosum agenesis and formation of bilateral Probst bundles indicative of the failure of callosally projecting neurons to extend across the midline (PubMed:27339102). Mice with a triple gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 display impaired ability to stay on a rotarod and increased spontaneous locomotion (PubMed:27339102). These mice display an increased number of excitatory synapses in the apical dendritic regions of hippocampus neurons, an increase in the complexity of dendrite structure and increased total dendrite length (PubMed:22325200). One month after birth, mice with a triple gene disruption that lack Rtn4r, Rtn4rl1 and Rtn4rl2 show a significant reduction in the survival of motoneurons (PubMed:26335717). Compared to wild-type or single mutants, cerebellar granule cells from mice lacking Rtn4r, Rtn4rl1 and Rtn4rl2 show decreased myelin-mediated inhibition of neurite outgrowth, an inhibition that is strongly decreased on myelin deficient in Mag, Rtn4 and Omg (PubMed:22406547). Mice lacking both Rtn4r and Rtn4rl1 show increased axon regeneration after injury; the same effect is observed when Rtn4r, Rtn4rl1 and Rtn4rl2 are disrupted (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs further increases axon regeneration after injury (PubMed:22406547). Single gene disruption of Rtn4r, Rtn4rl1 and Rtn4rl2 and combined disruption of Rtn4r and Rtn4rl2 have no effect on axon regeneration (PubMed:22406547).|||N-glycosylated (PubMed:29095159). O-glycosylated. Contains terminal sialic acid groups on its glycan chains (By similarity).|||Perikaryon|||Receptor for RTN4, OMG and MAG (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:18411262, PubMed:22923615). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (PubMed:22406547). Can also bind heparin (PubMed:22406547). Intracellular signaling cascades are triggered via the coreceptor NGFR (By similarity). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200). Mediates axonal growth inhibition (By similarity). Mediates axonal growth inhibition and plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system (PubMed:11201742, PubMed:12089450, PubMed:15504325, PubMed:22923615). Plays a role in postnatal brain development (PubMed:27339102). Required for normal axon migration across the brain midline and normal formation of the corpus callosum (PubMed:27339102). Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG (PubMed:26335717). Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development (PubMed:20093372). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200).|||axon|||dendrite http://togogenome.org/gene/10090:Gm20908 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Csrnp3 ^@ http://purl.uniprot.org/uniprot/P59055|||http://purl.uniprot.org/uniprot/Q7TNU4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AXUD1 family.|||Binds to the consensus sequence 5'-AGAGTG-3' and has transcriptional activator activity. Plays a role in apoptosis.|||Detected only in the brain of 15 dpc, 18 dpc, newborn and P6 mice (at protein level).|||Expressed during embryonic development and also detected a week after birth. Expression decreases by 14 days after birth and is not detected in the adult (at protein level).|||Mice display no obvious defects in development, hematopoiesis or T-cell function. Deletion of Axud1, Csnrp2 and Csnrp3 together causes partial neonatal lethality, suggesting that they have redundant functions.|||Nucleus http://togogenome.org/gene/10090:Vmn1r69 ^@ http://purl.uniprot.org/uniprot/Q8VIC1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fmo2 ^@ http://purl.uniprot.org/uniprot/Q8K2I3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FMO family.|||Catalyzes the oxidative metabolism of numerous xenobiotics, including mainly therapeutic drugs and insecticides that contain a soft nucleophile, most commonly nitrogen and sulfur and participates to their bioactivation (PubMed:18930751). Catalyzes the S-oxygenation of the prodrug ethionamide (ETA) to the S-oxide (ETASO), the first step in its bioactivation following by the second oxygenation to the sulfinic acid but to a lesser extend (PubMed:18930751).|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Flt1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0A4|||http://purl.uniprot.org/uniprot/P35969 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-1169 is important for interaction with PLCG. Phosphorylation at Tyr-1213 is important for interaction with PIK3R1, PTPN11, GRB2, and PLCG. Phosphorylation at Tyr-1328 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Is probably dephosphorylated by PTPRB (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell membrane|||Embryonic lethality at about 9 dpc, due to defects in the formation and organization of the vascular network (PubMed:7596436, PubMed:9689083). Mice display abnormal blood island structures in the yolk sac, leading to defects in the organization of the vascular endothelium, excess growth and disorganization of embryonic and extraembryonic vasculature, including the endocardium and the microvasculature (PubMed:7596436). Reduced vascular sprout formation and migration (PubMed:14982871). Loss of retinal hyaloid vessel regression from postnatal day 3 (P3) to P8 (PubMed:30936473). Mice expressing a mutant protein that lacks the kinase domain survive and have no apparent phenotype (PubMed:9689083).|||Endosome|||Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA, VEGFB and PGF. Can also form a heterodimer with KDR. Interacts (tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1 and PTPN11. Probably interacts with PTPRB. Interacts with RACK1. Identified in a complex with CBL and CD2AP (By similarity).|||Membrane|||N-glycosylated.|||Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).|||The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding.|||Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (PubMed:30936473). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, and proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts. Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to the activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC, YES1 and PLCG, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 and PTK2/FAK1 (By similarity).|||Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation. http://togogenome.org/gene/10090:Eola1 ^@ http://purl.uniprot.org/uniprot/Q9D1F3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the EOLA family.|||Interacts with MT2A.|||May play a role in cell protection during the inflammatory response. In epithelial cells, negatively regulates IL6 production and apoptosis through the regulation of MT2A expression. http://togogenome.org/gene/10090:Pcdha10 ^@ http://purl.uniprot.org/uniprot/Q91Y20 ^@ Function|||Miscellaneous|||Subcellular Location Annotation ^@ Cell membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.|||The protocadherins alpha are expressed from a single gene cluster similarly to immunoglobulin and T-cell receptors. The N-terminal region containing the 6 extracellular cadherin domains, unique to each protocadherin alpha, is encoded by one of the large exons found in tandem array within the gene cluster. The C-terminal region, identical to all protocadherins alpha, is encoded by 3 shared exons. http://togogenome.org/gene/10090:Itgb6 ^@ http://purl.uniprot.org/uniprot/Q9Z0T9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin beta chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit (PubMed:10025398). Interacts with FLNB (By similarity). Interacts with HAX1 (By similarity). ITGAV:ITGB6 interacts with FBN1 (By similarity). ITGAV:ITGB6 interacts with TGFB1 (PubMed:10025398).|||Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for fibronectin and cytotactin (By similarity). It recognizes the sequence R-G-D in its ligands (PubMed:10025398). ITGAV:ITGB6 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (By similarity). Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:10025398).|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site.|||focal adhesion http://togogenome.org/gene/10090:Mst1 ^@ http://purl.uniprot.org/uniprot/P26928|||http://purl.uniprot.org/uniprot/Q3UZ05 ^@ Caution|||Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Plasminogen subfamily.|||Cleaved after Arg-488, probably by HPN/Hepsin, to yield the active form consisting of two disulfide-linked chains.|||Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts (via beta chain) with MST1R (via SEMA domain).|||Is expressed at low levels during gestation. Just before birth the level increases dramatically and remains stable afterwards.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Liver. Lower levels in lung, placenta and adrenal.|||Secreted|||The active site residues characteristic of serine proteases appear to be absent from this protein, which may therefore lack catalytic activity. http://togogenome.org/gene/10090:Mecp2 ^@ http://purl.uniprot.org/uniprot/Q9Z2D6 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).|||Interacts with FNBP3 (PubMed:9171351). Interacts with CDKL5 (By similarity). Interacts with ATRX; MECP2 recruits ATRX to pericentric heterochromatin in neuronal cells (PubMed:17296936). Interacts with NCOR2 (PubMed:23770565). Interacts with TBL1XR1; bridges interaction between MECP2 and NCOR1 (PubMed:28348241). Interacts with TBL1X; recruits TBL1X to the heterochromatin foci (By similarity).|||Nucleus|||Phosphorylated on Ser-421 by CaMK2 in brain upon synaptic activity, which attenuates its repressor activity and seems to regulate dendritic growth and spine maturation. Does not seem to be phosphorylated on Ser-421 in other tissues.|||Ten times higher expression levels than isoform A in brain (at protein level). http://togogenome.org/gene/10090:Fam124a ^@ http://purl.uniprot.org/uniprot/D3Z5V4 ^@ Similarity ^@ Belongs to the FAM124 family. http://togogenome.org/gene/10090:Siae ^@ http://purl.uniprot.org/uniprot/P70665 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Catalyzes the removal of O-acetyl ester groups from position 9 of the parent sialic acid, N-acetylneuraminic acid.|||Cytoplasm|||Disulfide-linked heterodimer of a small subunit and a large subunit.|||Inhibited by diisopropyl fluorophosphate and diethyl-P-nitrophenyl phosphate.|||Isoform 1 is widely expressed. Isoform 2 shows a more restricted distribution with highest expression in brain and ovary and lower levels in liver and thymus.|||Lysosome|||The lysosomal isoform is glycosylated.|||The two subunits are derived from a single precursor by proteolytic cleavage. http://togogenome.org/gene/10090:Epha8 ^@ http://purl.uniprot.org/uniprot/O09127 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Cell projection|||Early endosome membrane|||First detected at 10.5 dpc with high levels near the midline region of the tectum and to a lower extent in discrete regions of hindbrain, the dorsal horn, of the spinal cord and in the naso-lacrimal groove. The expression decreases at 12.5 dpc and is barely detectable at 17.5 dpc. Not detected at postnatal stages.|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). May also form heterodimers with other ephrin receptors. Interacts with FYN; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PIK3CG; regulates integrin-mediated cell adhesion to substrate. Interacts with TIAM1; regulates clathrin-mediated endocytosis of EPHA8. Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-independent but stimulated by EPHA8 ubiquitination.|||Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-615 is critical for association with FYN. Autophosphorylation on Tyr-838 modulates tyrosine kinase activity.|||Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth.|||Specifically expressed in the central nervous system.|||Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation. http://togogenome.org/gene/10090:Tom1l2 ^@ http://purl.uniprot.org/uniprot/Q5SRX1 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Acts as a MYO6/Myosin VI adapter protein that targets myosin VI to endocytic structures (By similarity). May also play a role in recruiting clathrin to endosomes (By similarity). May regulate growth factor-induced mitogenic signaling (By similarity).|||Belongs to the TOM1 family.|||Interacts with clathrin, SRC and TOLLIP (By similarity). Interacts with MYO6 (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||The GAT domain mediates interaction with TOLLIP.|||Ubiquitously expressed. Splicing pattern displays tissue specific variation. http://togogenome.org/gene/10090:Mtmr9 ^@ http://purl.uniprot.org/uniprot/Q9Z2D0 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an adapter for myotubularin-related phosphatases (PubMed:12890864). Increases lipid phosphatase MTMR6 catalytic activity, specifically towards phosphatidylinositol 3,5-bisphosphate, and MTMR6 binding affinity for phosphorylated phosphatidylinositols (By similarity). Positively regulates lipid phosphatase MTMR7 catalytic activity (PubMed:12890864). The formation of the MTMR6-MTMR9 complex, stabilizes both MTMR6 and MTMR9 protein levels (By similarity). Plays a role in the late stages of macropinocytosis possibly by regulating MTMR6-mediated dephosphorylation of phosphatidylinositol 3-phosphate in membrane ruffles (By similarity). Negatively regulates DNA damage-induced apoptosis, in part via its association with MTMR6 (By similarity). Does not bind mono-, di- and tri-phosphorylated phosphatidylinositols, phosphatidic acid and phosphatidylserine (By similarity).|||Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 333 in the dsPTPase catalytic loop, suggesting that it has no carboxypeptidase activity.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Endoplasmic reticulum|||Homodimer (PubMed:12890864). Heterodimer (via C-terminus) with lipid phosphatase MTMR6 (via C-terminus) (PubMed:12890864). Heterodimer (via coiled coil domain) with lipid phosphatase MTMR7 (via C-terminus) (PubMed:12890864).|||The GRAM domain is required for cell membrane localization.|||The coiled coil domain mediates interaction with MTMR9.|||perinuclear region|||ruffle membrane http://togogenome.org/gene/10090:Inpp5j ^@ http://purl.uniprot.org/uniprot/P59644 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.|||Cytoplasm|||Inositol 5-phosphatase, which converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate. Also converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate in vitro. May be involved in modulation of the function of inositol and phosphatidylinositol polyphosphate-binding proteins that are present at membranes ruffles.|||The 5 Arg-Ser-Xaa-Ser-Xaa-Xaa (RSXSXX) motifs may constitute binding sites for the 14-3-3 protein. http://togogenome.org/gene/10090:Ift140 ^@ http://purl.uniprot.org/uniprot/E9PY46 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs) (By similarity). Plays a pivotal role in proper development and function of ciliated cells through its role in ciliogenesis and/or cilium maintenance (PubMed:22282595). Required for the development and maintenance of the outer segments of rod and cone photoreceptor cells. Plays a role in maintenance and the delivery of opsin to the outer segment of photoreceptor cells (PubMed:24619649).|||Component of the IFT complex A (IFT-A). IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts (via C-terminal region) with IFT122 (via C-terminal region). Interacts with TTC25. Interacts with TTC21A.|||Defects in Ift140 are the cause of cauliflower (cauli) phenotype, a mouse model for human asphyxiating thoracic dystrophy (Jeune syndrome). Embryos die at 13.5 dpc and exhibit exencephaly, anophthalmia, severely disorganized ribs with extensive exostoses, vertebral and palatal defects, agenesis/hypoplasia of the craniofacial skeleton, and polydactyly of the hindlimbs. Cilia morphology in limb buds is severely disrupted with a broader and bulbous appearance.|||Mice exhibit pronounced postnatal renal cyst formation and renal failure. Significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis seen in highly cystic, but not precystic kidneys. Disrupted cilia assembly in postnatal day 5 (P5) kidneys (PubMed:22282595). Mice exhibit cone cell degeneration and opsin accumulation in the plasma membrane of the inner segments of photoreceptor cells (PubMed:24619649).|||centrosome|||cilium|||cilium basal body http://togogenome.org/gene/10090:Pou3f4 ^@ http://purl.uniprot.org/uniprot/A6H6L6|||http://purl.uniprot.org/uniprot/P62515 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family. Class-3 subfamily.|||Brain specific.|||Interacts with HNRNPU.|||Nucleus|||Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain. http://togogenome.org/gene/10090:Ndrg3 ^@ http://purl.uniprot.org/uniprot/Q544I1|||http://purl.uniprot.org/uniprot/Q8VCV2|||http://purl.uniprot.org/uniprot/Q9QYF9 ^@ Developmental Stage|||Similarity|||Tissue Specificity ^@ Belongs to the NDRG family.|||Expressed at high levels in brain, followed by small intestine and kidney (at protein level). Also expressed in thymus.|||Its expression is already significant at 9.5 dpc, covering the entire embryo except the heart, and it shows only a slight increase in later developmental stages. http://togogenome.org/gene/10090:Mrpl42 ^@ http://purl.uniprot.org/uniprot/Q9CPV3 ^@ Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL42 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Has been found in the mitochondrial ribosome large and small subunits.|||Mitochondrion http://togogenome.org/gene/10090:Map3k19 ^@ http://purl.uniprot.org/uniprot/E9Q3S4 ^@ Similarity ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. http://togogenome.org/gene/10090:Yju2 ^@ http://purl.uniprot.org/uniprot/Q9D6J3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC16 family. YJU2 subfamily.|||Component of the spliceosome. Present in the activated B complex, the catalytically activated B* complex which catalyzes the branching, the catalytic step 1 C complex catalyzing the exon ligation, and the postcatalytic P complex containing the ligated exons (mRNA) and the excised lariat intron.|||Nucleus|||Part of the spliceosome which catalyzes two sequential transesterification reactions, first the excision of the non-coding intron from pre-mRNA and then the ligation of the coding exons to form the mature mRNA. Plays a role in stabilizing the structure of the spliceosome catalytic core and docking of the branch helix into the active site, producing 5'-exon and lariat intron-3'-intermediates. May protect cells from TP53-dependent apoptosis upon dsDNA break damage through association with PRP19-CD5L complex. http://togogenome.org/gene/10090:Cldn11 ^@ http://purl.uniprot.org/uniprot/Q60771 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the claudin family.|||Cell membrane|||Interacts with tetraspanin-3/TSPAN3 (PubMed:11309411). Interacts with OCLN (By similarity).|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Asphd2 ^@ http://purl.uniprot.org/uniprot/Q80VP9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the aspartyl/asparaginyl beta-hydroxylase family.|||May function as 2-oxoglutarate-dependent dioxygenase.|||Membrane http://togogenome.org/gene/10090:Thoc7 ^@ http://purl.uniprot.org/uniprot/Q7TMY4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the THOC7 family.|||Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling (By similarity). Interacts with NIF3L1 (PubMed:12951069). Interacts with THOC5 (By similarity).|||Cytoplasm|||Expressed at low levels in testis between P3 and P14. Expression in testis increases at P20 and reaches maximum levels in adult.|||Nucleus|||Nucleus speckle|||Required for efficient export of polyadenylated RNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Gng10 ^@ http://purl.uniprot.org/uniprot/Q9CXP8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Interacts with beta-1 and beta-2, but not with beta-3 (By similarity). http://togogenome.org/gene/10090:Pramel48 ^@ http://purl.uniprot.org/uniprot/A6H6A2|||http://purl.uniprot.org/uniprot/Q499F0|||http://purl.uniprot.org/uniprot/Q4VBX3|||http://purl.uniprot.org/uniprot/Q8C6K3 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Rccd1 ^@ http://purl.uniprot.org/uniprot/Q8BTU7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Found in a complex with KDM8. Interacts (via N-terminus) with KDM8 (via N-terminus).|||Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with KDM8. Possibly together with KDM8, is involved in proper mitotic spindle organization and chromosome segregation. Plays a role in regulating alpha-tubulin deacetylation and cytoskeletal microtubule stability, thereby promoting cell migration and TGF-beta-induced epithelial to mesenchymal transition (EMT), potentially through the inhibition of KDM8.|||Specifically hydroxylated (with R stereochemistry) at C-3 of ARG-141 by KDM8. http://togogenome.org/gene/10090:Scgb2b7 ^@ http://purl.uniprot.org/uniprot/D3YYY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Siah1a ^@ http://purl.uniprot.org/uniprot/P61092 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SINA (Seven in absentia) family.|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2 (By similarity). Required for completion of meiosis I in males (PubMed:11884614). Induces apoptosis in cooperation with PEG3 (PubMed:10681424). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (PubMed:24809345). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1.|||Homodimer. Component of some large E3 complex composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit its activity. Interacts with PEG3 (By similarity). Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with SNCAIP. Interacts with KHDRBS3. Interacts with SNCAIP. Interacts with HIPK2; the interaction is promoted by DAZAP2 and results in SIAH1-mediated ubiquitination and subsequent proteasomal degradation of HIPK2 (By similarity). Interacts with DAZAP2; the interaction is decreased following phosphorylation of DAZAP2 by HIPK2 (By similarity). Interacts with GAPDH; leading to stabilize SIAH1. Interacts with Bassoon/BSN and Piccolo/PLCO; these interactions negatively regulate SIAH1 E3 ligase activity. Interacts with DCC (By similarity). Interacts with AXIN1; catalyzes AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin-dependent degradation.|||May be induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response (PubMed:12417719). The relevance of such activity in vivo is however unclear and may not exist (PubMed:12417719). Induced by ATF4 in response to the unfolded protein response (UPR) (PubMed:24809345).|||Nucleus|||Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2 (By similarity).|||The RING-type zinc finger domain is essential for ubiquitin ligase activity.|||The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.|||Widely expressed at low level in embryos and adults. Expressed at higher level in testis. Due to the high similarity between SIAH1A and SIAH1B, it is difficult to distinguish its own tissue specificity. http://togogenome.org/gene/10090:Myo3b ^@ http://purl.uniprot.org/uniprot/F8VQ79|||http://purl.uniprot.org/uniprot/Q1EG27 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Expressed in the cochlear hair cells (at protein level) (PubMed:26754646). Expressed in utricle hair bundles (at protein level) (PubMed:26926603).|||In the C-terminal section; belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||In the N-terminal section; belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family.|||Interacts (via C-terminus) with ESPN (PubMed:26785147, PubMed:26926603). Interacts (via C-terminus) with ESPNL (PubMed:26926603).|||MYO3B single knockout mice do not exhibit early hearing impairment whereas mice with a double knockout of MYO3A and MYO3B are profoundly deaf at 1 month of age. Cochlear hair bundles have abnormally long stereocilia and show dynamic shape defects during development.|||Probable actin-based motor with a protein kinase activity (By similarity). Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern (PubMed:26754646). Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:22264607).|||cytoskeleton|||stereocilium http://togogenome.org/gene/10090:Elac1 ^@ http://purl.uniprot.org/uniprot/Q8VEB6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase Z family.|||Binds 2 Zn(2+) ions.|||Homodimer.|||Nucleus|||Zinc phosphodiesterase, which displays some tRNA 3'-processing endonuclease activity. Specifically involved in tRNA repair: acts downstream of the ribosome-associated quality control (RQC) pathway by removing a 2',3'-cyclic phosphate from tRNAs following cleavage by ANKZF1. tRNAs are then processed by TRNT1.|||cytosol http://togogenome.org/gene/10090:Tubgcp6 ^@ http://purl.uniprot.org/uniprot/G5E8P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TUBGCP family.|||Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6.|||Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.|||centrosome http://togogenome.org/gene/10090:Or55b10 ^@ http://purl.uniprot.org/uniprot/Q9WU94 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gins4 ^@ http://purl.uniprot.org/uniprot/Q99LZ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GINS4/SLD5 family.|||Chromosome|||Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex. Associated with ORC2. Interacts with HELB.|||Cytoplasm|||Highly abundant in testis. Weakly expressed in thymus and bone marrow.|||Nucleus|||Required for initiation of chromosomal DNA replication. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. http://togogenome.org/gene/10090:Ensa ^@ http://purl.uniprot.org/uniprot/P60840 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the endosulfine family.|||Cytoplasm|||Interacts (when phosphorylated at Ser-67) with PPP2R2D. Interacts with ABCC8. Interacts with SNCA; interaction is disrupted when phosphorylated at Ser-109 (By similarity).|||May be due to an intron retention.|||Phosphorylation at Ser-67 by GWL during mitosis is essential for interaction with PPP2R2D (PR55-delta) and subsequent inactivation of PP2A. Phosphorylated by PKA (By similarity).|||Present in striatum (at protein level).|||Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-67 during mitosis, specifically interacts with PPP2R2D (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase. Also acts as a stimulator of insulin secretion by interacting with sulfonylurea receptor (ABCC8), thereby preventing sulfonylurea from binding to its receptor and reducing K(ATP) channel currents (By similarity). http://togogenome.org/gene/10090:Taar2 ^@ http://purl.uniprot.org/uniprot/Q5QD17 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Lsm8 ^@ http://purl.uniprot.org/uniprot/Q6ZWM4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA. http://togogenome.org/gene/10090:Cacna1i ^@ http://purl.uniprot.org/uniprot/E9Q7P2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.|||Membrane|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. http://togogenome.org/gene/10090:Atp5b ^@ http://purl.uniprot.org/uniprot/P56480 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-133 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the ATPase alpha/beta chains family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). Interacts with PPIF (PubMed:21281446). Interacts with BCL2L1 isoform BCL-X(L); the interaction mediates the association of BCL2L1 isoform BCL-X(L) with the mitochondrial membrane F(1)F(0) ATP synthase and enhances neurons metabolic efficiency (By similarity). Interacts with CLN5 and PPT1 (PubMed:19941651). Interacts with S100A1; this interaction increases F1-ATPase activity (PubMed:17438143). Interacts with MTLN (By similarity). Interacts with TTC5/STRAP; the interaction results in decreased mitochondrial ATP production (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Il17rc ^@ http://purl.uniprot.org/uniprot/Q8BPI5|||http://purl.uniprot.org/uniprot/Q8K4C2 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Highly expressed in colonic epithelial cells (PubMed:19144317). Expressed in lung epithelial cells (PubMed:28813677). Expressed in macrophages (PubMed:19144317). Highly expressed in B-1a B cells and at a lower extent in B-1b and B-2 B cells (at protein level) (PubMed:26735852).|||Homodimer; disulfide-linked (By similarity). Heterodimer with IL17RA (PubMed:20554964). Heterodimerization with IL17RA is independent of the cytoplasmic tail. Associates with non-glycosylated IL17RA constitutively. Binding of IL17A and IL17F induces association with glycosylated IL17RA (PubMed:20554964). Forms complexes with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (By similarity). IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer forms predominantly complexes with IL17RC homodimer (By similarity). IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (By similarity). IL17RC chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (By similarity). Interacts (through SEFIR domain and extended downstream region) with TRAF3IP2/ACT1 (phosphorylated) (PubMed:20554964).|||Induced in lung epithelial cells upon bacterial and fungal infection. Up-regulated in lung epithelial cells by IL17F; this might account for a persistent activation via a positive feedback loop.|||Membrane|||Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:27923703, PubMed:19144317). Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:17911633, PubMed:20554964). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (By similarity). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (By similarity). Upon binding of IL17F homodimer triggers downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:28813677). Induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi (PubMed:28813677). Promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (PubMed:32076265). Binding of IL17A-IL17F to IL17RA-IL17RC heterodimeric receptor complex triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:20554964). Primarily induces neutrophil activation and recruitment at infection and inflammatory sites (PubMed:27923703). Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (PubMed:19144317). http://togogenome.org/gene/10090:Nrxn3 ^@ http://purl.uniprot.org/uniprot/Q6P9K9|||http://purl.uniprot.org/uniprot/Q8C985 ^@ Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neurexin family.|||Brain and arteries (at protein level).|||Contains an insert which is not supported by any other transcript and which does not match with the genome.|||Neuronal cell surface protein that may be involved in cell recognition and cell adhesion. May mediate intracellular signaling (By similarity).|||O-glycosylated; contains heparan sulfate. Heparan sulfate attachment is required for synapse development by mediating interactions with neuroligins.|||Presynaptic cell membrane|||Proccessed by alpha-secretase leading to the formation of an extracellular soluble protein as well as a C-terminal membrane-embedded fragment (CTF). Proteolysis of these CTFs by gamma-secretase releases intracellular domains (ICDs) and extracellular peptides (By similarity).|||Produced by alternative splicing.|||The laminin G-like domain 2 binds to NXPH1 (By similarity). Specific isoforms bind to alpha-dystroglycan (By similarity). The cytoplasmic C-terminal region binds to CASK (By similarity). Specific isoforms bind neuroligins NLGN1, NLGN2 and NLGN3 (By similarity). Interacts with CLSTN3 (PubMed:24094106, PubMed:24613359, PubMed:32434929).|||Weakly interacts with CBLN1 and CBLN2 (PubMed:21410790, PubMed:22220752, PubMed:29782851). Very weak binding, if any, to CBLN4 (PubMed:22220752, PubMed:29782851). Specific isoforms bind neuroligins NLGN1, NLGN2 and NLGN3 (By similarity). Interacts with CLSTN3 (PubMed:24613359, PubMed:32434929). http://togogenome.org/gene/10090:Ddx39b ^@ http://purl.uniprot.org/uniprot/Q9Z1N5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DECD subfamily.|||Cytoplasm|||Homodimer, and heterodimer with DDX39A. Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have dynamic structure involving ATP-dependent remodeling; in the complex bridges ALYREF/THOC4 and the THO complex, and, in a ATP-dependent manner, ALYREF/THOC4 and SARNP/CIP29. Component of the spliceosome. Interacts directly with U2AF2. Interacts with RBM8A, RNPS1 and SRRM1, FYTTD1/UIF, THOC1, MX1 and POLDIP3. Interacts with LUZP4.|||Involved in nuclear export of spliced and unspliced mRNA. Assembling component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. May undergo several rounds of ATP hydrolysis during assembly of TREX to drive subsequent loading of components such as ALYREF/THOC and CHTOP onto mRNA. Also associates with pre-mRNA independent of ALYREF/THOC4 and the THO complex. Involved in the nuclear export of intronless mRNA; the ATP-bound form is proposed to recruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPase activity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATP hydrolysis is thought to trigger the dissociation from RNA to allow the association of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved in transcription elongation and genome stability.|||Nucleus|||Nucleus speckle|||Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2; the effect of ALYREF/THOC4 is reported conflictingly with [] reporting a stimulatory effect.|||The helicase C-terminal domain mediates interaction with ALYREF/THOC4. http://togogenome.org/gene/10090:Poc5 ^@ http://purl.uniprot.org/uniprot/Q9DBS8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the POC5 family.|||Essential for the assembly of the distal half of centrioles, required for centriole elongation.|||Hyperphosphorylated during recruitment to procentrioles in G2/M phase.|||Interacts with CETN2 and CETN3.|||centriole http://togogenome.org/gene/10090:Krt33a ^@ http://purl.uniprot.org/uniprot/Q8K0Y2 ^@ Miscellaneous|||Similarity ^@ Belongs to the intermediate filament family.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Med26 ^@ http://purl.uniprot.org/uniprot/Q7TN02 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 26 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity). Interacts with CEBPB (when not methylated)(PubMed:20111005).|||Nucleus http://togogenome.org/gene/10090:Htr5b ^@ http://purl.uniprot.org/uniprot/G3X9C6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Shcbp1 ^@ http://purl.uniprot.org/uniprot/Q9Z179 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated upon growth inhibition.|||Expressed in spleen, lung and heart with higher expression in testis. No expression in brain, liver and skeletal muscle. Elevated expression in actively cycling cells.|||Interacts directly with isoform p52shc of SHC1 via its SH2 domain (PubMed:10086341). Interacts with TRIM71; leading to enhanced SHCBP1 protein stability (PubMed:22508726). Interacts with both members of the centralspindlin complex, KIF23 and RACGAP1 (By similarity).|||May play a role in signaling pathways governing cellular proliferation, cell growth and differentiation. May be a component of a novel signaling pathway downstream of Shc. Acts as a positive regulator of FGF signaling in neural progenitor cells.|||Midbody|||spindle http://togogenome.org/gene/10090:H2bc27 ^@ http://purl.uniprot.org/uniprot/Q9D2U9 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The human orthologous protein seems not to exist.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Selenom ^@ http://purl.uniprot.org/uniprot/Q8VHC3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the selenoprotein M/F family.|||Endoplasmic reticulum|||Golgi apparatus|||May function as a thiol-disulfide oxidoreductase that participates in disulfide bond formation.|||Widely expressed. Highly expressed in brain.|||perinuclear region http://togogenome.org/gene/10090:Gm28553 ^@ http://purl.uniprot.org/uniprot/A0A9L6KDW0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Dcaf7 ^@ http://purl.uniprot.org/uniprot/P61963 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat DCAF7 family.|||Cytoplasm|||Highly expressed in 10.5 dpc embryo limb buds, in an overlapping pattern with PTCH1 and GLI1.|||Interacts with DYRK1A, DYRK1B and DIAPH1. Interacts with DDB1. Interacts with ZNF703 (By similarity).|||Involved in craniofacial development. Acts upstream of the EDN1 pathway and is required for formation of the upper jaw equivalent, the palatoquadrate. The activity required for EDN1 pathway function differs between the first and second arches. Associates with DIAPH1 and controls GLI1 transcriptional activity. Could be involved in skin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or2r2 ^@ http://purl.uniprot.org/uniprot/B2RT27 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ip6k3 ^@ http://purl.uniprot.org/uniprot/Q8BWD2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the inositol phosphokinase (IPK) family.|||Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4 (By similarity).|||Cytoplasm|||Highly expressed in cerebellum, brain cortex, kidney, thymus and lung. Detected at lower levels in hippocampus, testis, heart and olfactory bulb. http://togogenome.org/gene/10090:Akr1a1 ^@ http://purl.uniprot.org/uniprot/Q540D7|||http://purl.uniprot.org/uniprot/Q80XJ7|||http://purl.uniprot.org/uniprot/Q9JII6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the aldo/keto reductase family.|||Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (By similarity) (PubMed:22820017, PubMed:15769935, PubMed:20410296). Plays an important role in ascorbic acid biosynthesis by catalyzing the reduction of D-glucuronic acid and D-glucurono-gamma-lactone (PubMed:20410296, PubMed:15769935, PubMed:22820017). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes. Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). Involved in the detoxification of lipid-derived aldehydes like acrolein (By similarity). Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs (By similarity). Displays no reductase activity towards retinoids (By similarity).|||Cell membrane|||Deficient mice develop and grow normally but suffer severe osteopenia and spontaneous fractures with stresses that increase ascorbic acid requirements, such as pregnancy or castration (PubMed:20410296). Deficient mice exhibit reduced asorbic acid and D,L-glyceraldehyde levels. The activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis, are suppressed in AKR1A knockout mice (PubMed:22820017, PubMed:20410296).|||Detected at high levels in several tissues including neural ectoderm, gut endoderm, somites, branchial arches, otic vesicles, limb buds and tail bud.|||Fear memory increases expression 7-fold.|||Membrane|||Monomer.|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Slc9a6 ^@ http://purl.uniprot.org/uniprot/A1L3P4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Developmentally regulated in area CA1 of the hippocamus, peaking at around postnatal day 50 and declining thereafter.|||Early endosome membrane|||Endosomal Na(+), K(+)/H(+) antiporter. Mediates the electroneutral exchange of endosomal luminal H(+) for a cytosolic Na(+) or K(+). By facilitating proton efflux, SLC9A6 counteracts the acidity generated by vacuolar (V)-ATPase, thereby limiting luminal acidification. Responsible for alkalizing and maintaining the endosomal pH, and consequently in, e.g., endosome maturation and trafficking of recycling endosomal cargo (PubMed:17005858, PubMed:21413028, PubMed:24035762, PubMed:34526390). Plays a critical role during neurodevelopment by regulating synaptic development and plasticity (PubMed:21413028, PubMed:34526390). Implicated in the maintenance of cell polarity in a manner that is dependent on its ability to modulate intravesicular pH (By similarity). Regulates intracelular pH in some specialized cells, osteoclasts and stereocilia where this transporter localizes to the plasma membrane (PubMed:17005858, PubMed:21413028).|||Endosome membrane|||Glycosylated.|||Homodimer. Interacts with RACK1; regulates the distribution of SLC9A6 between endosomes and the plasma membrane.|||Late endosome membrane|||Recycling endosome membrane|||The SLC9A6 null mice show a 10-20% increased mortality after birth, yet the surviving mice do not display any obvious difference. Behavioral tests reveal a modest motor hyperactivity associated with coordination deficits and limited ataxia. Neurons from these deficient mice exhibit endosomal hyperacidification, as well as impoverished neuronal arborization and attendant circuit dysfunction.|||Ubiquitinated (in vitro). http://togogenome.org/gene/10090:Man2b1 ^@ http://purl.uniprot.org/uniprot/O09159 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 38 family.|||Binds 1 zinc ion per subunit.|||Lysosome|||Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. http://togogenome.org/gene/10090:Oxct1 ^@ http://purl.uniprot.org/uniprot/Q9D0K2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 3-oxoacid CoA-transferase family.|||Homodimer. Only one subunit is competent to transfer the CoA moiety to the acceptor carboxylate (3-oxo acid).|||Key enzyme for ketone body catabolism. Catalyzes the first, rate-limiting step of ketone body utilization in extrahepatic tissues, by transferring coenzyme A (CoA) from a donor thiolester species (succinyl-CoA) to an acceptor carboxylate (acetoacetate), and produces acetoacetyl-CoA. Acetoacetyl-CoA is further metabolized by acetoacetyl-CoA thiolase into two acetyl-CoA molecules which enter the citric acid cycle for energy production (By similarity). Forms a dimeric enzyme where both of the subunits are able to form enzyme-CoA thiolester intermediates, but only one subunit is competent to transfer the CoA moiety to the acceptor (3-oxo acid) carboxylate and produce a new acyl-CoA. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Mnx1 ^@ http://purl.uniprot.org/uniprot/A2RSX2 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sppl2c ^@ http://purl.uniprot.org/uniprot/A2A6C4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase A22B family.|||Endoplasmic reticulum membrane|||Glycosylated.|||Highly expressed in testis where it is primarily localised in spermatids (at protein level).|||In round spermatids, acts as a scaffold protein supporting FREY1 in IZUMO1 recruitment at the endoplasmic reticulum membrane and coordination of IZUMO1 complex assembly. Stabilizes FREY1 at the endoplasmic reticulum membrane through interaction. May recruit IZUMO1 interaction partners.|||Interacts (via active sites) with FREY; the interaction stabilizes FREY1 protein and inhibits SPPL2C proteolytic activity.|||Knockout males produce normal-sized litters when bred with wild-type females (PubMed:35960805, PubMed:30733280). Mutants show a partial loss of elongated spermatids and reduced motility of mature spermatozoa, but preserved fertility. Matings of male and female mutant mice exhibit reduced litter sizes (PubMed:30733280). FREY1 and SPPL2C double knockout mice are normozoospermic infertile (PubMed:35960805).|||No difference in cleavage specificity compared to isoform 1.|||Sperm-specific intramembrane-cleaving aspartic protease (I-CLiP) that cleaves distinct tail-anchored proteins and SNARE proteins (PubMed:35960805, PubMed:30733280, PubMed:30733281). In elongated spermatids, modulates intracellular Ca(2+) homeostasis by controlling PLN abundance through proteolytic cleavage (PubMed:30733280). During spermatogenesis, processes SNARE proteins and impacts vesicular trafficking which supports compartmental reorganization in maturating spermatids and may play a role in formation of the acrosome (PubMed:30733281).|||The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP. http://togogenome.org/gene/10090:Oas1g ^@ http://purl.uniprot.org/uniprot/Q8K469 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the 2-5A synthase family.|||Cytoplasm http://togogenome.org/gene/10090:Ada ^@ http://purl.uniprot.org/uniprot/P03958|||http://purl.uniprot.org/uniprot/Q4FK28 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.|||Binds 1 zinc ion per subunit.|||Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:9272950, PubMed:8634299, PubMed:10720488, PubMed:8672487, PubMed:8942668). Plays an important role in purine metabolism and in adenosine homeostasis (PubMed:9272950, PubMed:10720488). Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events (PubMed:11435465). Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (By similarity). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (By similarity). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (By similarity). Stimulates plasminogen activation (By similarity). Plays a role in male fertility (By similarity). Plays a protective role in early postimplantation embryonic development (PubMed:9272950).|||Cell junction|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle lumen|||Detected in brain neurons in the median emninence (at protein level) (PubMed:8783262). Expressed in secondary deciduum (at protein level) (PubMed:9272950). Found in all tissues, occurs in large amounts in T-lymphocytes and, at the time of weaning, in gastrointestinal tissues.|||Expressed in trophoblast at 7.5 dpc and 9.5 dpc.|||Interacts with DPP4 (via extracellular domain). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4.|||Lethal at perinatal stages. Fetuses are viable up to 18 dpc, but after this survival decreases rapidly. Fewer that 10% of mutant pups are born live, and these die within hours after birth. Mutant fetuses display much higher than normal levels of adenosine and dATP, respiratory distress, hepatocellular degeneration and necrosis. Prenatal lethality can be avoided using an ADA expression vector with a trophoblast-specific promoter. Mutant mice die after about three weeks due to immunodeficiency, disturbances in purine metabolism and severe lung inflammation.|||Lysosome http://togogenome.org/gene/10090:Selenbp1 ^@ http://purl.uniprot.org/uniprot/P17563 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the selenium-binding protein family.|||Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria (PubMed:29255262). Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity).|||Highly expressed in liver, kidney and, to a lesser extent, lung.|||Interacts with USP33.|||Membrane|||Nucleus|||SELENBP1 knockout results in accumulation of dimethylsulfoxide in the plasma. Methanethiol oxidase activity measured in tissues from knockout mice is significantly lower that in normal tissues.|||The N-terminus is blocked.|||cytosol http://togogenome.org/gene/10090:Mamstr ^@ http://purl.uniprot.org/uniprot/Q0ZCJ7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in skeletal muscle, brain, placenta and spleen.|||Interacts with MEF2C.|||Nucleus|||Transcriptional coactivator. Stimulates the transcriptional activity of MEF2C. Stimulates MYOD1 activity in part via MEF2, resulting in an enhancement of skeletal muscle differentiation. http://togogenome.org/gene/10090:Or12k7 ^@ http://purl.uniprot.org/uniprot/Q8VFP3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:B3galnt2 ^@ http://purl.uniprot.org/uniprot/Q8BG28 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward any acceptor substrate. Involved in alpha-dystroglycan (DAG1) glycosylation: acts coordinately with GTDC2/POMGnT2 to synthesize a GalNAc-beta3-GlcNAc-beta-terminus at the 4-position of protein O-mannose in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan, which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (By similarity).|||Endoplasmic reticulum|||Golgi apparatus membrane|||N-glycosylated.|||Present in testis (at protein level). In testis, it is mainly detected in the middle layers of seminiferous tubules at stages XII to II. Strongly expressed in primary and secondary spermatocytes and early round spermatids, but not in spermatogonia, elongating or elongated spermatids, or in Leydig or Sertoli cells. http://togogenome.org/gene/10090:Cep43 ^@ http://purl.uniprot.org/uniprot/Q66JX5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP43 family.|||Homodimer. Part of a ternary complex that contains CEP350, CEP43 and MAPRE1. Interacts directly with CEP350 and MAPRE1. Interacts with CEP19. Interacts (via N-terminus) with CEP350 (via C-terminus).|||Required for anchoring microtubules to the centrosomes. Required for ciliation.|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Semp2l1 ^@ http://purl.uniprot.org/uniprot/E9PXF3 ^@ Similarity ^@ Belongs to the peptidase C48 family. http://togogenome.org/gene/10090:Use1 ^@ http://purl.uniprot.org/uniprot/E9Q496|||http://purl.uniprot.org/uniprot/Q9CQ56 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the USE1 family.|||Component of a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L and SEC22B. Interacts directly with STX18 (By similarity).|||Endoplasmic reticulum membrane|||Membrane|||SNARE that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER. http://togogenome.org/gene/10090:Bsx ^@ http://purl.uniprot.org/uniprot/Q810B3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the distal-less homeobox family.|||Cytoplasm|||DNA binding protein that function as transcriptional activator. Is essential for normal postnatal growth and nursing. Is an essential factor for neuronal neuropeptide Y and agouti-related peptide function and locomotory behavior in the control of energy balance.|||Expressed in brain. In brain, it is restricted to a few specific developing brain structures such as pineal gland, telencephalic septum, hypothalamic pre-mammillary body and arcuate nucleus.|||Expressed in early embryonic stages of epiphysis development from 9.5 dpc onwards.|||Nucleus http://togogenome.org/gene/10090:Armc6 ^@ http://purl.uniprot.org/uniprot/Q8BNU0 ^@ PTM|||Similarity ^@ Belongs to the ARMC6 family.|||Methylated at His-238 by METTL9. http://togogenome.org/gene/10090:Pex5 ^@ http://purl.uniprot.org/uniprot/O09012 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxisomal targeting signal receptor family.|||Cys-11 acts as a sensor of redox state. In response to oxidative stress, monoubiquitination at Cys-11 is prevented.|||Does not mediate translocation of peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.|||In addition to promoting peroxisomal translocation of proteins containing a PTS1 peroxisomal targeting signal, mediates peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal via its interaction with PEX7. Interaction with PEX7 only takes place when PEX7 is associated with cargo proteins containing a PTS2 peroxisomal targeting signal. PEX7 along with PTS2-containing cargo proteins are then translocated through the PEX13-PEX14 docking complex together with PEX5.|||Interacts (via WxxxF/Y and LVxEF motifs) with PEX14; promoting translocation through the PEX13-PEX14 docking complex. Interacts with PEX12. Interacts (Cys-linked ubiquitinated) with ZFAND6. Interacts (when ubiquitinated at Lys-210) with p62/SQSTM1.|||Interacts with PEX7, promoting peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal.|||Liver-specific knockout mice display a growth retardation from the third postnatal week resulting in a 30% to 40% lower body weight than control mice at the age of 7 weeks (PubMed:15732085). Thereafter, mice tend to catch up in growth, and by 3 months their weight is not different from control mice (PubMed:15732085). Throughout this period, the mice look healthy, are fertile and liver function is unaffected (PubMed:15732085). However, 10-week-old mutant mice display a severe hepatomegaly due to hypertrophic and hyperplastic hepatocytes (PubMed:15732085). Mutant mice survive but develope extensive liver tumors from 12 months on (PubMed:15732085). Peroxisomes are absent in mutant hepatocytes and multiple ultrastructural alterations are noticed, smooth endoplasmic reticulum proliferation, and accumulation of lipid droplets and lysosomes (PubMed:15732085). Most prominent is the abnormal structure of the inner mitochondrial membrane (PubMed:15732085). This is accompanied by severely reduced activities of complex I, III, and V and a collapse of the mitochondrial inner membrane potential (PubMed:15732085). Liver-specific knockout mice display severely impaired oxidation of 2-methylhexadecanoic acid, the bile acid intermediate trihydroxycholestanoic acid (THCA), and tetradecanedioic acid (PubMed:17442273). In contrast, mitochondrial beta-oxidation rates of palmitate are doubled (PubMed:17442273). Lens-specific knockout mice develop cataracts (PubMed:33389129).|||Monoubiquitinated at Cys-11 by PEX2 during PEX5 passage through the retrotranslocation channel (By similarity). Cys-11 monoubiquitination acts as a recognition signal for the PEX1-PEX6 complex and is required for PEX5 extraction and export from peroxisomes. Monoubiquitination at Cys-11 is removed by USP9X in the cytosol, resetting PEX5 for a subsequent import cycle (By similarity). When PEX5 recycling is compromised, polyubiquitinated by PEX10 during its passage through the retrotranslocation channel, leading to its degradation (By similarity). Monoubiquitination at Lys-472 by TRIM37 promotes its stability by preventing its polyubiquitination and degradation by the proteasome. Ubiquitination at Lys-527 is not mediated by the PEX2-PEX10-PEX12 ligase complex and is not related to PEX5 recycling. Monoubiquitinated at Lys-210 by PEX2 following phosphorylation by ATM in response to starvation or reactive oxygen species (ROS), leading to PEX5 recognition by p62/SQSTM1 and induction of pexophagy (By similarity).|||Peroxisome matrix|||Phosphorylated at Ser-141 by ATM in response to reactive oxygen species (ROS), promoting monoubiquitination at Lys-210 and induction of pexophagy.|||Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type). Binds to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, and translocates them into the peroxisome matrix by passing through the PEX13-PEX14 docking complex along with cargo proteins. PEX5 receptor is then retrotranslocated into the cytosol, leading to release of bound cargo in the peroxisome matrix, and reset for a subsequent peroxisome import cycle.|||The TPR repeats mediate interaction with proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type).|||The WxxxF/Y motifs mediate interaction with PEX14, promoting association with the PEX13-PEX14 docking complex.|||The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are required for PEX5 retrotranslocation and recycling. AH2 mediates interaction with lumenal side of the PEX2-PEX10-PEX12 ligase complex, while AH1 is required for extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex.|||cytosol http://togogenome.org/gene/10090:Or2b28 ^@ http://purl.uniprot.org/uniprot/Q8VFG2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Syngr2 ^@ http://purl.uniprot.org/uniprot/O55101 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptogyrin family.|||Cytoplasmic vesicle membrane|||May be tyrosine phosphorylated by Src.|||May play a role in regulated exocytosis. In neuronal cells, modulates the localization of synaptophysin/SYP into synaptic-like microvesicles and may therefore play a role in the formation and/or the maturation of this vesicles. May also play a role in GLUT4 storage and transport to the plasma membrane.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Akt1s1 ^@ http://purl.uniprot.org/uniprot/Q9D1F4 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Associated component of the mechanistic target of rapamycin complex 1 (mTORC1), which contains core MTOR, MLST8 and RPTOR (By similarity). Dissociates from mTORC1 in response to insulin treatment (By similarity). mTORC1 binds to and is inhibited by FKBP12-rapamycin (By similarity). Interacts (via TOS motif) with RPTOR; interaction is direct (By similarity). The phosphorylated form interacts with 14-3-3 proteins (By similarity).|||Negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (By similarity). In absence of insulin and nutrients, AKT1S1 associates with the mTORC1 complex and directly inhibits mTORC1 activity by blocking the MTOR substrate-recruitment site (By similarity). In response to insulin and nutrients, AKT1S1 dissociates from mTORC1 (By similarity). Its activity is dependent on its phosphorylation state and binding to 14-3-3 (By similarity). May also play a role in nerve growth factor-mediated neuroprotection (PubMed:14973226, PubMed:16397181).|||Phosphorylated by AKT1; phosphorylation takes place in response to insulin treatment and promotes AKT1S1 interaction with 14-3-3 proteins, leading to relieve its inhibitor activity (By similarity). Phosphorylated by MTOR following mTORC1 activation, inhibiting AKT1S1 inhibitor activity: phosphorylation by MTOR probably serves as a feedback loop that relieves inhibition from AKT1S1 in response to mTORC1 inactivation (By similarity). Phosphorylation at Thr-247 by DYRK3 relieves inhibitory function on mTORC1 (By similarity).|||The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.|||cytosol http://togogenome.org/gene/10090:Styx ^@ http://purl.uniprot.org/uniprot/Q60969 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Catalytically inactive phosphatase (PubMed:7592916). Acts as a nuclear anchor for MAPK1/MAPK3 (ERK1/ERK2) (By similarity). Modulates cell-fate decisions and cell migration by spatiotemporal regulation of MAPK1/MAPK3 (ERK1/ERK2) (By similarity). By binding to the F-box of FBXW7, prevents the assembly of FBXW7 into the SCF E3 ubiquitin-protein ligase complex, and thereby inhibits degradation of its substrates (By similarity). Plays a role in spermatogenesis (PubMed:11842224).|||Contains a Gly residue instead of a conserved Cys residue at position 120 in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. The binding pocket is however sufficiently preserved to bind phosphorylated substrates, and may protect them from phosphatases.|||Interacts with MAPK1; independently of MAPK1 phosphorylation status (By similarity). Interacts with CARHSP1/Crhsp-24 (PubMed:11842224). Interacts (via FQQ motif) with FBXW7 (via F-box domain); the interaction is direct and prevents FBXW7 interaction with SKP1, a component of the SCF(FBXW7) complex (By similarity).|||Males are infertile due to a disrupted spermatid development, resulting in a >1000-fold decrease in spermatozoa production.|||Nucleus|||Widely expressed with highest levels in muscle, testis and brain (PubMed:7592916). In testis, expression starts 13-14 days after birth and is limited to the seminiferous tubule and to round and elongating spermatids (PubMed:11842224). Expression is low in condensing spermatids and pachytene spermatocytes, and absent in spermatogonia, spermatozoa and somatic Sertoli cells (PubMed:11842224).|||cytosol http://togogenome.org/gene/10090:Uap1 ^@ http://purl.uniprot.org/uniprot/Q91YN5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UDPGP type 1 family.|||Converts UTP and GlcNAc-1-P into UDP-GlcNAc, and UTP and GalNAc-1-P into UDP-GalNAc. Isoform AGX1 has 2 to 3 times higher activity towards GalNAc-1-P, while isoform AGX2 has 8 times more activity towards GlcNAc-1-P (By similarity).|||Cytoplasm|||Monomer and homodimer. Isoform AGX1 is a homodimer. Isoform AGX2 is a monomer (By similarity). http://togogenome.org/gene/10090:Fhip1a ^@ http://purl.uniprot.org/uniprot/Q505K2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the FHIP family.|||May be a component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3. May interact directly with AKTIP/FTS.|||Probable component of the FTS/Hook/FHIP complex (FHF complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell. http://togogenome.org/gene/10090:Lhx6 ^@ http://purl.uniprot.org/uniprot/E9QN32|||http://purl.uniprot.org/uniprot/H9H9T0|||http://purl.uniprot.org/uniprot/Q9R1R0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain specific. Expressed by neurons in the amygdala that are activated by reproductive olfactory stimuli and project in regions of the hypothalamus involved in reproduction (at protein level).|||Interacts with LDB1 (via the LIM zinc-binding domains).|||Mice lacking Lhx6 fail to thrive, develop general weakness and die within the first 2 weeks after birth.|||Nucleus|||Probable transcription factor required for the expression of a subset of genes involved in interneurons migration and development. Functions in the specification of cortical interneuron subtypes and in the migration of GABAergic interneuron precursors from the subpallium to the cerebral cortex.|||Several sequencing errors.|||Specifically expressed during brain maturation from 14.5 dpc to P2 by a subset of tangentially migrating interneurons. Barely detectable in adult brain. Isoform 1 expression peaks at P2 and remains high in adulthood compared to isoform 2. Expressed in preoptic area, hypothalamic regions and the first branchial arch at 9.5 dpc. Expressed uniformly in the odontogenic mesenchyme of the first branchial arch prior to initiation of tooth development. During odontogenesis expression is restricted to the mesenchyme participating in the formation of individual teeth. Expressed in olfactory bulb, arcuate nucleus, medial glanglionic eminence and preoptic area at 13.5 dpc and 14.5 dpc. Expression spread to the cortex and hippocampus at P1.0. Preferentially expressed in parvalbumin or somatostatin positive cortical interneurons. http://togogenome.org/gene/10090:Tff2 ^@ http://purl.uniprot.org/uniprot/Q9QX97 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Sft2d3 ^@ http://purl.uniprot.org/uniprot/Q9CSV6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SFT2 family.|||May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.|||Membrane http://togogenome.org/gene/10090:Prkrip1 ^@ http://purl.uniprot.org/uniprot/Q9CWV6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRKRIP1 family.|||Broadly expressed, with highest levels in liver, kidney, brain and heart.|||By IL11.|||Component of the pre-catalytic and post-catalytic spliceosome complexes (By similarity). Interacts with EIF2AK2.|||Nucleus|||Required for pre-mRNA splicing as component of the spliceosome (By similarity). Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity.|||nucleolus http://togogenome.org/gene/10090:Glrb ^@ http://purl.uniprot.org/uniprot/A1KR23|||http://purl.uniprot.org/uniprot/P48168 ^@ Caution|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRB sub-subfamily.|||Cell membrane|||Cytoplasm|||Defects in Glrb cause the spastic condition which is characterized by muscle rigidity, tremors, myoclonic jerks, pronounced startle reaction, abnormal gait and impaired righting ability (PubMed:7920630). Neurons from the ventral horn of the spinal cord display reduced inhibitory postsynaptic currents (PubMed:12809985). Likewise, hypoglossal neurons display a dramatic reduction in the frequency and amplitude of postsynaptic inhibitory currents (PubMed:16672662).|||Detected in spinal cord, brain and brain stem, especially in the periolivary region, spinal nuclei, trigeminal nucleus, medulla oblongata, pons and midbrain. Detected in the inner plexiform layer of the retina (at protein level) (PubMed:22592841). High levels of expression in cortex, hippocampus, thalamus and cerebellum (PubMed:7920630). Detected in spinal cord (PubMed:7946325).|||Glycine receptors are ligand-gated chloride channels. GLRB does not form ligand-gated ion channels by itself, but is part of heteromeric ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:12809985). Heteropentameric channels composed of GLRB and GLRA1 are activated by lower glycine levels than homopentameric GLRA1. Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents (PubMed:12809985, PubMed:16672662).|||Heteropentamer composed of GLRB and GLRA1. Heteropentamer composed of GLRB and GLRA2. Heteropentamer composed of GLRB and GLRA3. Heteropentamer composed of two GLRA1 and three GLRB subunits. Heteropentamer composed of three GLRA1 and two GLRB subunits. Interacts with GLRA1 (By similarity). Interacts with GPHN.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Postsynaptic cell membrane|||Synapse|||Synaptic cell membrane|||dendrite http://togogenome.org/gene/10090:Lamb3 ^@ http://purl.uniprot.org/uniprot/Q61087 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Domain VI is globular.|||Found in the basement membranes (major component).|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Beta-3 is a subunit of laminin-5 (laminin-332 or epiligrin/kalinin/nicein). Interacts with ECM1 (By similarity).|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Smc2 ^@ http://purl.uniprot.org/uniprot/Q3ULS2|||http://purl.uniprot.org/uniprot/Q8CG48 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMC family. SMC2 subfamily.|||Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases (By similarity).|||Chromosome|||Cytoplasm|||Forms a heterodimer with SMC4. Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: BRRN1/CAPH, CNAP1/CAPD2 and CAPG (By similarity).|||Nucleus|||The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC4, forming a V-shaped heterodimer. http://togogenome.org/gene/10090:Cd47 ^@ http://purl.uniprot.org/uniprot/Q61735 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Adhesive protein that mediates cell-to-cell interactions (By similarity). Acts as receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation of heterotrimeric G proteins (By similarity). Involved in signal transduction, cardiovascular homeostasis, inflammation, apoptosis, angiogenesis, cellular self-renewal, and immunoregulation (PubMed:27742621, PubMed:20610415, PubMed:23591719). Plays a role in modulating pulmonary endothelin EDN1 signaling (PubMed:27742621). Modulates nitrous oxide (NO) signaling, in response to THBS1, hence playing a role as a pressor agent, supporting blood pressure (PubMed:20610415). Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity). Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells (By similarity). Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation (By similarity). Positively modulates FAS-dependent apoptosis in T-cells, perhaps by enhancing FAS clustering (PubMed:15917238). Plays a role in suppressing angiogenesis and may be involved in metabolic dysregulation during normal aging (PubMed:32679764). In response to THBS1, negatively modulates wound healing (PubMed:18156939). Inhibits stem cell self-renewal, in response to THBS1, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 (PubMed:23591719). May play a role in membrane transport and/or integrin dependent signal transduction (By similarity). May prevent premature elimination of red blood cells (PubMed:10856220).|||Cell membrane|||Expression increases in lungs following chronic hypoxia (PubMed:27742621). Expression in arteries increases in normal aging (PubMed:32679764).|||Knockout endothelial cells have increased basal endothelial NO synthase (eNOS) activity (PubMed:20610415). Abnormally low resting mean arterial pressure (MAP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (PubMed:20610415). Endothelin receptors EDNRA and EDNRB are significantly decreased in blood vessels (PubMed:20610415). Suppresses hypoxia-mediated increase in right-ventricle maximum systolic pressure and pulmonary arterial thickening (PubMed:27742621). Suppresses hypoxia-mediated induction of pulmonary endothelin EDN1 and endothelin receptor EDNRA (PubMed:27742621). Abolishes age-associated induction of arterial THBS1 mRNA (PubMed:32679764). Increased proliferation and migration of arterial endothelial cells and enhanced sprouting angiogenesis (PubMed:32679764). Increased expression of matrix metalloproteinases MMP2 and MMP9 in endothelial cells from aged mice (at protein level) (PubMed:32679764). Improved glucose tolerance and insulin sensitivity in aged individuals by comparison with age-matched controls (PubMed:32679764). Enhanced survival of full-thickness skin grafts, with increased numbers of functional vessels in wound beds (PubMed:18156939). Increased mRNA levels for POU5F1/Oct4, SOX2, MYC/c-Myc, KLF4 and NES/Nestin; significant up-regulation in spleen; moderately increased expression in lung, except for KLF4 (PubMed:23591719).|||Monomer (By similarity). Interacts with THBS1 (via the C-terminal domain) (By similarity). Interacts with SIRPA (PubMed:10856220). Interacts with FAS/CD95; interaction may be enhanced by functional activation (By similarity). Interacts with SIRPG, UBQLN1 and UBQLN2 (By similarity). May interact with fibrinogen (By similarity). http://togogenome.org/gene/10090:Tmem35b ^@ http://purl.uniprot.org/uniprot/Q3U0Y2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the DoxX family.|||Membrane http://togogenome.org/gene/10090:Cxcl5 ^@ http://purl.uniprot.org/uniprot/P50228 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||By lipopolysaccharide (LPS).|||GCP-2(1-78) and GCP-2(9-78) are produced by proteolytic cleavage after secretion from fibroblasts and epithelial cells. GCP-2(9-78) is the most prominent form. A number of additional N-terminal (processed between pos. 41 and 48) and C-terminal (processed between pos. 118 and 132) processed forms have been identified, probably also representing intermediate states.|||May participate in the recruitment of inflammatory cells by injured or infected tissue. GCP-2(1-78) and, more potent, GCP-2(9-78) attract neutrophils and are involved in neutrophil activation.|||Monomer. Homodimer.|||Secreted http://togogenome.org/gene/10090:H60c ^@ http://purl.uniprot.org/uniprot/B1B213 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NKG2D ligand family.|||Cell membrane|||Expressed in skin, and weakly in large intestine.|||Ligand for the KLRK1 immunosurveillance receptor. Binding to KLRK1 stimulates cell lysis in vitro. http://togogenome.org/gene/10090:Xrcc2 ^@ http://purl.uniprot.org/uniprot/Q9CX47 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RecA family. RAD51 subfamily.|||Expressed at low level in somatic tissues and at high level in testis.|||Interacts with RAD51D. Part of the BCDX2 complex consisting of RAD51B, RAD51C, RAD51D and XRCC2; the complex has a ring-like structure arranged into a flat disk around a central channel. In the absence of DNA, the BCDX2 subcomplex XRCC2:RAD51D formed a multimeric ring structure; in the presence of single-stranded DNA it formed a filamentous structure with the ssDNA (By similarity).|||Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA (By similarity).|||Nucleus http://togogenome.org/gene/10090:Eef1akmt3 ^@ http://purl.uniprot.org/uniprot/D3YWP0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METTL21 family.|||Cytoplasm|||Interacts with members of the heat shock protein 70 and 90 families and of the TCP-1 chaperonin family, as well as with HSPD1, STIP1 and tubulin; at least some of these proteins may be methylation substrates.|||Protein-lysine methyltransferase that selectively mono-, di- and trimethylates 'Lys-165' of the translation elongation factors EEF1A1 and EEF1A2 in an aminoacyl-tRNA and GTP-dependent manner (By similarity). EEF1A1 methylation by EEF1AKMT3 is dynamic as well as inducible by stress conditions, such as ER-stress, and plays a regulatory role on mRNA translation (PubMed:28108655).|||centrosome http://togogenome.org/gene/10090:Orai3 ^@ http://purl.uniprot.org/uniprot/A3KCG3|||http://purl.uniprot.org/uniprot/Q6P8G8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Orai family.|||Ca(2+) release-activated Ca(2+)-like (CRAC-like) channel subunit which mediates Ca(2+) influx and increase in Ca(2+)-selective current by synergy with the Ca(2+) sensor, STIM1.|||Cell membrane|||Interacts with CRACR2A/EFCAB4B.|||Membrane http://togogenome.org/gene/10090:Cd44 ^@ http://purl.uniprot.org/uniprot/A2APM1|||http://purl.uniprot.org/uniprot/A2APM2|||http://purl.uniprot.org/uniprot/A2APM3|||http://purl.uniprot.org/uniprot/A2APM4|||http://purl.uniprot.org/uniprot/P15379|||http://purl.uniprot.org/uniprot/Q3U8S1|||http://purl.uniprot.org/uniprot/Q80X37 ^@ Caution|||Domain|||Function|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment. Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection. Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:8343954, PubMed:25065622). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (By similarity).|||Expressed in the intestinal epithelium.|||Interacts with PKN2 (PubMed:17403031). Interacts with TIAM1 and TIAM2 (PubMed:19893486). Interacts with HA, as well as other glycosaminoglycans, collagen, laminin, and fibronectin via its N-terminal segment (PubMed:24606063). Interacts with UNC119. Interacts with PDPN (via extracellular domain); this interaction is required for PDPN-mediated directional migration and regulation of lamellipodia extension/stabilization during cell spreading and migration (By similarity). Interacts with RDX, EZR and MSN (via FERM domain) (PubMed:9472040, PubMed:18753140). Interacts with EGFR (By similarity). Interacts with CD74; this complex is essential for the MIF-induced signaling cascade that results in B cell survival (PubMed:8343954).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||O-glycosylated; contains chondroitin sulfate glycans which can be more or less sulfated.|||Phosphorylated; activation of PKC results in the dephosphorylation of Ser-742 (constitutive phosphorylation site), and the phosphorylation of Ser-708.|||Secreted|||The lectin-like LINK domain is responsible for hyaluronan binding.|||Two allelic forms of this glycoprotein, PGP-1.1 and PGP-1.2, have been reported. The expressed product is PGP-1.1 (Ly-24.1).|||microvillus http://togogenome.org/gene/10090:Terf2ip ^@ http://purl.uniprot.org/uniprot/Q91VL8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes.|||Belongs to the RAP1 family.|||Chromosome|||Cytoplasm|||Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Binds to TERF2 (but not TERF1) with its C-terminus. Interacts with SLX4/BTBD12 (By similarity). Interacts with TERF2; the interaction is direct. Does not interact with TERF1. Associates with the I-kappa-B-kinase (IKK) core complex, composed of CHUK, IKBKB and IKBKG.|||Mice are viable and fertile. No major telomere dysfunction such as telomere fusions are observed. An increased telomere fragility and recombination due to defects in HDR are however present. Mice with conditional deletion in stratified epithelia display shorter telomeres and developed skin hyperpigmentation in adulthood.|||Nucleus|||Shares a bidirectional promoter with KARS1 (PubMed:14659874). This shared promoter with an essential gene complicated the task when generating knockout mice; the problem was overcome by generating conditional knockout strategies (PubMed:20339076, PubMed:20622869).|||telomere http://togogenome.org/gene/10090:Riok3 ^@ http://purl.uniprot.org/uniprot/Q9DBU3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated (in vitro).|||Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.|||Cytoplasm|||Interacts with CASP10. Interacts with IRF3; RIOK3 probably mediates the interaction of TBK1 with IRF3. Associated with 40S pre-ribosomal particles.|||Involved in regulation of type I interferon (IFN)-dependent immune response which plays a critical role in the innate immune response against DNA and RNA viruses. May act as an adapter protein essential for the recruitment of TBK1 to IRF3. Phosphorylates IFIH1 on 'Ser-828' interfering with IFIH1 filament assembly on long dsRNA and resulting in attenuated IFIH1-signaling. Can inhibit CASP10 isoform 7-mediated activation of the NF-kappaB signaling pathway. May play a role in the biogenesis of the 40S ribosomal subunit. Involved in the processing of 21S pre-rRNA to the mature 18S rRNA. http://togogenome.org/gene/10090:Sord ^@ http://purl.uniprot.org/uniprot/Q64442 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family.|||Binds 1 zinc ion per subunit.|||Detected early in spermatogenesis. Detected in condensing spermatids (at protein level) and is up-regulated during late spermatogenesis.|||Homotetramer.|||Inhibited in vitro by p-hydroxymercuribenzoate, EDTA, l,l0-phenanthroline and N-ethylmaleimide.|||Mitochondrion membrane|||Polyol dehydrogenase that catalyzes the reversible NAD(+)-dependent oxidation of various sugar alcohols (By similarity). Is active with D-sorbitol (D-glucitol) leading to the C2-oxidized product D-fructose (PubMed:6852349). Is a key enzyme in the polyol pathway that interconverts glucose and fructose via sorbitol, which constitutes an important alternate route for glucose metabolism (By similarity). May play a role in sperm motility by using sorbitol as an alternative energy source for sperm motility and protein tyrosine phosphorylation (PubMed:18799757). Has no activity on ethanol. Cannot use NADP(+) as the electron acceptor (PubMed:6852349).|||Testis has the highest level of expression, followed by kidney, liver, and lung. Low levels of expression are also observed in lens, brain, and skeletal muscle. Expressed in sperm flagellum and very low expression in the sperm head.|||flagellum http://togogenome.org/gene/10090:Slc25a14 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQJ8|||http://purl.uniprot.org/uniprot/Q9Z2B2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Homotetramer.|||Mainly expressed in brain, particularly abundant in cortex, hippocampus thalamus, amygdala and hypothalamus (PubMed:10928996). Highly expressed in heart and kidney, but not liver or lung (at protein level) (PubMed:11701769). In the nervous system, expressed in cortex, basal ganglia, substantia nigra, cerebellum, and spinal cord (at protein level) (PubMed:11701769).|||Membrane|||Mitochondrion inner membrane|||Transports inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate and glutamate and tricarboxylates. May catalyze the export of sulfite and thiosulfate (the hydrogen sulfide degradation products) from the mitochondria, thereby modulating the level of the hydrogen sulfide. Also can mediate a very low unidirectional transport of anions including sulfate, phosphate, (S)-malate, citrate, L-aspartate and L-glutamate. Maintains oxidative balance (through uncoupling activities) and ATP production (by modifying mitochondrial membrane potential). Is able to transport protons across lipid membranes. Also exhibits transmembrane chloride transport activity to a lesser extent (By similarity). May modify mitochondrial respiratory efficiency and mitochondrial oxidant production (PubMed:11701769). http://togogenome.org/gene/10090:Tssk4 ^@ http://purl.uniprot.org/uniprot/Q9D411 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autophosphorylation on Thr-197.|||Activated by autophosphorylation on Thr-197. ODF2 potentiates the autophosphorylation activity of TSSK4 at Thr-197.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Catalytically inactive.|||Detected throughout spermiogenesis, in round spermatids, elongated spermatids, and mature spermatozoa (PubMed:23054012, PubMed:20729278, PubMed:26940607). Detected at low levels on postnatal day 14, with significantly increased expression on postnatal day 16. Expression levels are unchanged after postnatal day 16 (PubMed:17927909, PubMed:20729278).|||Expressed in spermatocytes and mature sperm (at protein level) (PubMed:20729278, PubMed:23054012, PubMed:25361759, PubMed:26940607). Highly expressed in the spleen, heart and testis (PubMed:17927909, PubMed:20729278, PubMed:23054012). Isoform 2, isoform 3, and isoform 4: Expressed at highest level in testis and heart and at low levels in the liver, spleen, kidney, brain and thymus (PubMed:17927909).|||Homodimer (PubMed:17927909, PubMed:23054012). Interacts with HSP90; this interaction stabilizes and activates TSSK4 (PubMed:23599433). Interacts with ODF2 (via C-terminus); this interaction promotes ODF2 phosphorylation on 'Ser-95' (PubMed:25361759, PubMed:26961893). May interact with CREM (PubMed:26940607). Interacts with CREB1; this interaction facilitates CREB1 phosphorylation on 'Ser-133' (By similarity). Interacts with QRICH2 (By similarity).|||Intron retention.|||Male mice are subfertile due to reduced sperm motility. The reduced motility is due to morphological defects in the sperm flagellum at the midpiece-principal piece junction caused by the disordered arrangement of doublet microtubules and outer dense fibers.|||Mg(2+) and Mn(2+) were both present in the kinase buffer but Mg(2+) is likely to be the in vivo cofactor.|||Serine/threonine kinase which is involved in male germ cell development and in mature sperm function (PubMed:17927909, PubMed:23599433, PubMed:23054012, PubMed:25361759, PubMed:26940607). May be involved in the Cre/Creb signaling pathway (PubMed:26940607). Phosphorylates CREB1 on 'Ser-133' in vitro and can stimulate Cre/Creb pathway in cells (By similarity). Phosphorylates CREM on 'Ser-116' in vitro (PubMed:26940607). Phosphorylates ODF2 on 'Ser-95' (PubMed:26961893).|||Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation.|||acrosome|||flagellum http://togogenome.org/gene/10090:Itga2b ^@ http://purl.uniprot.org/uniprot/Q9QUM0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-IIb associates with beta-3. Directly interacts with RNF181. Interacts (via C-terminus cytoplasmic tail region) with CIB1; the interaction is direct and calcium-dependent. Interacts (via C-terminus cytoplasmic tail region) with CIB2, CIB3 and CIB4; the interactions are stabilized/increased in a calcium and magnesium-dependent manner (By similarity). ITGA2B:ITGB3 interacts with PPIA/CYPA; the interaction is ROS and PPIase activity-dependent and is increased in the presence of thrombin (PubMed:24429998).|||Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface.|||Membrane http://togogenome.org/gene/10090:Nanos3 ^@ http://purl.uniprot.org/uniprot/P60324 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nanos family.|||Binds mRNA from germ cells. Interacts with PUM2.|||Cytoplasm|||Expressed in undifferentiated spermatogonial cells.|||Found in the male and female gonads of early embryo and, after birth, it is found only in the testis. Expressed in primordial germ cells (PGCs) until 14.5 dpc in male gonad and until 13.5 dpc in female gonad; after this age its expression disappears and then it is found after birth only in male germ cells.|||Nucleus|||P-body|||Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase. Affects cell proliferation probably by repressing translation of specific mRNAs. Maintains the germ cell lineage by suppressing both Bax-dependent and -independent apoptotic pathways. Essential in the early stage embryo to protect the migrating primordial germ cells (PGCs) from apoptosis.|||Stress granule|||The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. It is essential for the translation repression activity of the protein. http://togogenome.org/gene/10090:Mfap2 ^@ http://purl.uniprot.org/uniprot/P55002|||http://purl.uniprot.org/uniprot/Q99PM0 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MFAP family.|||Component of the elastin-associated microfibrils.|||Forms a ternary complex with BGN and ELN. Interacts with FBN1 (via N-terminal domain) and FBN2.|||Forms intermolecular disulfide bonds either with other MAGP-1 molecules or with other components of the microfibrils. May form transglutaminase cross-links.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||O-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Cep57 ^@ http://purl.uniprot.org/uniprot/B8JJE7|||http://purl.uniprot.org/uniprot/Q8CEE0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the translokin family.|||Centrosomal protein which may be required for microtubule attachment to centrosomes. May act by forming ring-like structures around microtubules. Mediates nuclear translocation and mitogenic activity of the internalized growth factor FGF2.|||Cytoplasm|||Interacts with FGF2 and RAP80. Does not interact with FGF1 or FGF2 isoform 24 kDa (By similarity). Homodimer and homooligomer. Interacts with microtubules.|||Nucleus|||The C-terminal region mediates the interaction with microtubules and is able to nucleate and bundles microtubules in vitro.|||The centrosome localization domain (CLD) region mediates the localization to centrosomes and homooligomerization.|||Ubiquitous (at protein level). Expressed in testis, predominantly in round spermatids. Low expression is detected in other tissues.|||centrosome http://togogenome.org/gene/10090:Hrk ^@ http://purl.uniprot.org/uniprot/P62816 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with BCL2 and BCL2L1. Interacts with C1QBP (By similarity).|||Membrane|||Mitochondrion|||Promotes apoptosis.|||The BH3 motif is required for the induction of cell death. http://togogenome.org/gene/10090:Tdrd1 ^@ http://purl.uniprot.org/uniprot/Q99MV1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TDRD1 family.|||Cytoplasm|||Found in a mRNP complex, at least composed of TDRD1, TDRD6, TDRD7 and DDX4. Interacts with MAEL. Interacts with PIWIL1, PIWIL2 and PIWIL4 (when methylated on arginine residues). Interacts with TDRD12.|||Male sterility because of postnatal spermatogenic defects due to demethylation and subsequent derepression of transposable elements. Piwi-associated small RNA profiles are altered, piRNPs accepting the entry of abundant cellular transcripts into the piRNA pathway and accumulating piRNAs with a profile that is drastically different from wild-type. Piwi proteins are delocalized from the nucleus to the cytoplasm.|||Plays a central role during spermatogenesis by participating in the repression transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Required for the localization of Piwi proteins to the meiotic nuage. Involved in the piRNA metabolic process by ensuring the entry of correct transcripts into the normal piRNA pool and limiting the entry of cellular transcripts into the piRNA pathway. May act by allowing the recruitment of piRNA biogenesis or loading factors that ensure the correct entry of transcripts and piRNAs into Piwi proteins.|||Testis and ovary specific. Present in germ-line cells and is most abundant in fetal prospermatogonia and postnatal primary spermatocytes (at protein level).|||Tudor domains 2 and 3 have higher affinity for arginine-methylated peptides, tudor domain 1 is a poor binder due to an impaired aromatic cage. http://togogenome.org/gene/10090:Zfp316 ^@ http://purl.uniprot.org/uniprot/Q6PGE4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Metap1 ^@ http://purl.uniprot.org/uniprot/Q4VAA9|||http://purl.uniprot.org/uniprot/Q8BP48 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the 60S ribosomal subunit of the 80S translational complex.|||Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.|||Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.|||Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with zinc, cobalt, manganese or divalent iron ions. Has high activity with zinc; zinc cofactor is transferred into the active site region by the ZNG1 zinc chaperone.|||Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).|||Cytoplasm|||The C6H2-type zinc finger recruits ZNG1, promoting zinc cofactor transfer in the peptidase domain of METAP1. http://togogenome.org/gene/10090:Armcx5 ^@ http://purl.uniprot.org/uniprot/Q3UZB0 ^@ Similarity|||Tissue Specificity ^@ Belongs to the eutherian X-chromosome-specific Armcx family.|||Highly expressed in the developing neural tissues, neural crest derivatives and hind limbs. http://togogenome.org/gene/10090:Orm3 ^@ http://purl.uniprot.org/uniprot/J3JRU4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain (By similarity). Appears to function in modulating the activity of the immune system during the acute-phase reaction.|||Secreted http://togogenome.org/gene/10090:Gja6 ^@ http://purl.uniprot.org/uniprot/A0A654ID52|||http://purl.uniprot.org/uniprot/Q6S5G4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family.|||Belongs to the connexin family. Alpha-type (group II) subfamily.|||Cell membrane|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Gm20814 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Dtwd2 ^@ http://purl.uniprot.org/uniprot/B2RTH8|||http://purl.uniprot.org/uniprot/B7ZP35|||http://purl.uniprot.org/uniprot/Q9D0U1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TDD superfamily. DTWD2 family.|||Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20a in the D-loop of several cytoplasmic tRNAs (acp3U(20a)). Also has a weak activity to form acp3U at position 20 in the D-loop of tRNAs (acp3U(20)).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Selenop ^@ http://purl.uniprot.org/uniprot/P70274 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the selenoprotein P family.|||In the kidney, expressed in the cortex with no expression observed in the medulla (at protein level) (PubMed:18174160). Expressed by the liver and secreted in plasma (PubMed:9687017).|||Might be responsible for some of the extracellular antioxidant defense properties of selenium or might be involved in the transport of selenium (By similarity). May supply selenium to tissues such as brain and testis.|||Phosphorylation sites are present in the extracellular medium.|||Secreted|||The C-terminus is not required for endocytic uptake in the proximal tubule epithelium. http://togogenome.org/gene/10090:H3f3b ^@ http://purl.uniprot.org/uniprot/P84244 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed throughout the cell cycle independently of DNA synthesis.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes. metaphase chromosomes.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains (By similarity). Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).|||Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 and Lys-80. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with HIRA, a chaperone required for its incorporation into nucleosomes. Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3). Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity). Interacts with ASF1A, MCM2, NASP and SPT2 (By similarity).|||Ubiquitinated. Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.|||Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. http://togogenome.org/gene/10090:Itpa ^@ http://purl.uniprot.org/uniprot/Q60I30|||http://purl.uniprot.org/uniprot/Q9D892 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAM1 NTPase family.|||Binds 1 divalent metal cation per subunit; can use either Mg(2+) or Mn(2+).|||Cytoplasm|||Homodimer.|||Pups die about 2 weeks after birth with growth retardation and heart failure. Accumulates ITP in erythrocytes. Accumulates inosine in RNA and deoxyinosine in DNA.|||Pyrophosphatase that hydrolyzes the non-canonical purine (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.|||Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. http://togogenome.org/gene/10090:B3galt5 ^@ http://purl.uniprot.org/uniprot/Q9JI67 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Catalyzes the transfer of Gal to GlcNAc-based acceptors with a preference for the core3 O-linked glycan GlcNAc(beta1,3)GalNAc structure. Can use glycolipid LC3Cer as an efficient acceptor. Also catalyzes the transfer of Gal to the terminal GalNAc unit of the globoside GB4, thereby synthesizing the glycolipid GB5, also known as the stage-specific embryonic antigen-3 (SSEA-3).|||Expressed in brain and kidney.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Slc38a3 ^@ http://purl.uniprot.org/uniprot/Q9DCP2 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Expressed predominantly in liver, moderately expressed in kidney and brain, and barely detectable in heart and muscle (PubMed:10716701). Within liver, expressed in hepatocytes (PubMed:10716701). Not detected in testis (PubMed:10716701). Expressed in cells of the ganglion cell layer, in soma of some cells of the inner nuclear layer (at protein level) (PubMed:18689705). Expressed in the inner segments of photoreceptor cells (PubMed:18689705).|||Fei et al (PMID:10823827) shows that the transport process is electrogenic with a Na(+):L-glutamine stoichiometry of 2:1, contrary to the conclusions of Chaudhry et al (PMID:10619430) who finds that the transport is electroneutral with a Na(+):L-glutamine stoichiometry of 1:1 (By similarity). Chaudhry et al (PMID:11742981) shows that this electrogenic transport describes by Fei et al (PMID:10823827) would correspond to an amino acid-gated H(+) conductance that is not stoichiometrically coupled to the amino acid transport but which influences the ionic gradients that drive the amino acid transport (By similarity).|||Symporter that cotransports specific neutral amino acids and sodium ions, coupled to an H(+) antiporter activity (PubMed:30017230, PubMed:18689705, PubMed:29561757, PubMed:15899884, PubMed:16249471, PubMed:10716701). Mainly participates in the glutamate-GABA-glutamine cycle in brain where it transports L-glutamine from astrocytes in the intercellular space for the replenishment of both neurotransmitters glutamate and gamma-aminobutyric acid (GABA) in neurons and also functions as the major influx transporter in ganglion cells mediating the uptake of glutamine (PubMed:30017230, PubMed:29561757, PubMed:18689705). The transport activity is specific for L-glutamine, L-histidine and L-asparagine (PubMed:16249471, PubMed:10716701, PubMed:15899884, PubMed:18689705, PubMed:29561757, PubMed:30017230). The transport is electroneutral coupled to the cotransport of 1 Na(+) and the antiport of 1 H(+) (By similarity). The transport is pH dependent, saturable, Li(+) tolerant and functions in both direction depending on the concentration gradients of its substrates and cotransported ions (PubMed:16249471, PubMed:10716701, PubMed:18689705). Also mediates an amino acid-gated H(+) conductance that is not stoichiometrically coupled to the amino acid transport but which influences the ionic gradients that drive the amino acid transport (By similarity). In addition, may play a role in nitrogen metabolism, amino acid homeostasis, glucose metabolism and renal ammoniagenesis (PubMed:26490457).|||Up-regulated during renal ammoniagenesis and urinary ammonium excretion (PubMed:19458124). Up-regulated during acute acidosis (PubMed:24854847). Down-regulated by chronic treatment by insulin in hepatocytes (PubMed:15899884). Up-regulated by acute treatment by insulin (PubMed:15899884). http://togogenome.org/gene/10090:Ifna5 ^@ http://purl.uniprot.org/uniprot/Q810G2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Rpl17 ^@ http://purl.uniprot.org/uniprot/Q9CPR4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL22 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Slc30a3 ^@ http://purl.uniprot.org/uniprot/P97441|||http://purl.uniprot.org/uniprot/Q3TMQ7|||http://purl.uniprot.org/uniprot/Q6NZC3|||http://purl.uniprot.org/uniprot/S4R169 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Expression is restricted to brain (at protein level). In the brain, most abundant in hippocampus and cerebral cortex. The mRNA is also detected in testis, expression being restricted to germ cells and highest in pachytene spermatocytes and round spermatids.|||Homodimer. Homodimerization is negligible compared to the human protein. It could explain the lower efficiency of zinc transport. Interacts with TMEM163 (By similarity).|||Homozygous knockout mice lacking Slc30a3 do not display overt phenotype with morphology, body weight, lifespan, fertility, litter size being normal (PubMed:9990090). Zinc ions are eliminated from synaptic vesicles in brain of the knockout mice and the overall levels of zinc in brain is decreased (PubMed:9990090).|||In brain expression is negligible at birth, then increases linearly, reaching a maximum at about 3 weeks postpartum.|||Late endosome membrane|||Lysosome membrane|||Membrane|||Probable proton-coupled zinc ion antiporter mediating the import of zinc from cytoplasm into synaptic vesicles and participating to cellular zinc ion homeostasis in the brain.|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Apbb2 ^@ http://purl.uniprot.org/uniprot/Q9DBR4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early endosome|||Endoplasmic reticulum|||Expressed in the brain, retinal lens and muscle cells (at protein level).|||Golgi apparatus|||Interacts (via C-terminus) with APP (via C-terminus) (PubMed:18650440). Interacts with APLP2 (via cytoplasmic domain) (By similarity).|||Knockout mice develop cataracts from 16 months of age with defects such as ulcer-like anomalies in the cornea, and opacity in the lens cortex or wider lens. Decreased muscle strength, however clasping ability is unaffected (PubMed:25757569). Impaired spatial memory retrieval and learning (PubMed:27734846). Reduced branching of hippocampal neurites and increased fragmentation of neuromuscular junctions (PubMed:27734846). APBB1 and APBB2 double knockout mice show progressive retinal lens disruption from 1 month of age, morphologically lenses show massive vacuolization, lens capsule rupture and disruption of the lens fiber cells organization. Decreased muscle strength, however clasping ability is unaffected (PubMed:25757569, PubMed:27734846). Defects in peripheral motor function including balance and coordination, reduced environmental anxiety, reduced hippocampal basal synaptic transmission and synaptic plasticity (PubMed:27734846).|||Plays a role in the maintenance of lens transparency, and may also play a role in muscle cell strength (PubMed:25757569, PubMed:27734846). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (PubMed:27734846). Activates transcription of APP (By similarity). http://togogenome.org/gene/10090:Ddx3x ^@ http://purl.uniprot.org/uniprot/Q3TQX5|||http://purl.uniprot.org/uniprot/Q62167 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.|||Cell membrane|||Cytoplasm|||Encoded by an chromosome X-linked gene which escapes X chromosome inactivation (XCI) in females, but exhibits developmental- and tissue-specific differences in escape from XCI. DDX3Y, its homolog on chromosome Y, is located in the Y non-recombinant portion (By similarity). In 8 to 16 cell stage embryos, expression from paternal and maternal copies of DDX3X is detected. Paternally derived DDX3X is preferentially inactivated in extraembryonic tissues of embryos from 6.5 dpc (PubMed:27179789).|||Expressed in ovary, including in germinal vesicle immature and metaphase II (MII) stage oocytes (at protein level) (PubMed:8948440, PubMed:25050112). In the brain, expressed in the granule cells of the cerebellum and dentate gyrus, the pyramidal cells of the hippocampus, the ependymal cells lining the ventricles, choroid plexi and olfactory bulb. Also accumulates in the thalamic nuclei, the dorsal region of the colliculi and the pontine nucleus (PubMed:8948440).|||Homodimer; can bind RNA as a monomer and as a dimer/oligomer. Interacts with TDRD3. When phosphorylated, interacts with IRF3; the interaction facilitates the phosphorylation and activation of IRF3 by IKBKE. Directly interacts with XPO1/CRM1. The interaction with XPO1/CMR1 is dependent on the DDX3X nuclear export signal motif and XPO1 interaction with GTPase RAN in its active GTP-bound form. Weakly interacts with TBKBP1/SINTBAD. Directly interacts with TRAF3; this interaction stimulates TRAF3 'Lys-63' ubiquitination. Interacts with CSNK1E in a Wnt-dependent manner; this interaction greatly enhances CSNK1E affinity for ATP, stimulates its kinase activity and promotes CSNK1E-mediated DVL2 phosphorylation. In the presence of RNA, the interaction is decreased. Also interacts with CSNK1D and stimulates its kinase activity. Interacts with TRPV4; this interaction is decreased when the TRPV4 channel is activated, leading to DDX3X relocalization to the nucleus. Interacts with MAP3K14/NIK. Directly interacts with CHUK/IKKA after physiological activation of the TLR7 and TLR8 pathways; this interaction enhances CHUK autophosphorylation. May associate with EIF4F complex, composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. Directly interacts with EIF4E in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability. Directly interacts with EIF4G1 in an RNA-independent manner. DDX3X competes with EIF4G1 for interaction with EIF4E. Interacts with EIF4A1 and EIF2S1 in an RNA-independent manner. Associates with the eukaryotic translation initiation factor 3 (eIF-3) complex, including with EIF3B and EIF3C subunits. Directly interacts with IKBKE/IKKE; this interaction stimulates IKBKE activating autophosphorylation and is induced upon viral infection. Interacts with TBK1. Interacts with SP1; this interaction potentiates SP1-induced CDKN1A/WAF1/CIP1 transcription. Interacts with GSK3A and GSK3B. Interacts with several death receptors, inclusing FAS, TNFRSF10A and TNFRSF10B. Recruited to TNFRSF10B in the absence of receptor stimulation. When TNFRSF10B is stimulated, further recruited to the receptor and cleaved by caspases. A large proteolytic fragment remains associated with TNFRSF10B. Interacts (via C-terminus) with NXF1/TAP; this interaction may be partly involved in DDX3X nuclear export and in NXF1 localization to stress granules. Identified in an mRNP complex, composed of at least DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1/2, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. The interaction with IGF2BP1/2 is RNA-dependent. Directly interacts with PABPC1/PABP1 in an RNA-independent manner. This interaction increases in stressed cells and decreases during cell recovery. Interacts (via C-terminus) with MAVS/IPS-1; this interaction potentiates MAVS-mediated IFNB induction. Interacts with ERCC6/CBS. Interacts with DHX33 in an RNA-independent manner. Interacts with DDX5 in the cytoplasm; this interaction may be more efficient when both proteins are unphosphorylated. Interacts with RIGI. Interacts with IFIH1/MDA5. Interacts with NCAPH; this interaction may be important for the NCAPH localization at condensing chromosomes during mitosis (By similarity). Interacts with NLRP3 (via NACHT domain) under inflammasome-activating conditions (PubMed:31511697). Interacts with CAPRIN1. Interacts with HNF4A and NR0B2/SHP in an RNA-independent manner; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. Interacts with CREBBP/CBP. Interacts with EP300/p300. Interacts with gamma-tubulin. Interacts with phosphorylated TP53. Directly interacts with RELA/p65; this interaction may trap RELA in the cytoplasm, impairing nuclear relocalization upon TNF activating signals (By similarity).|||In mutant males, loss of DDX3X leads to early post-implantation lethality. In mutant females with a maternally inherited Ddx3x null allele, paternal X chromosome inactivation affects trophoblast differentiation, which leads to aberrant placental layers and defective vascularization in placental labyrinth. These placental abnormalities impair maternal blood supply to the embryo and ultimately lead to fetal growth restriction and lethality. Heterozygous females with a paternally inherited null allele are born at the expected Mendelian ratio, develop normally and are indistinguishable from their littermate controls (PubMed:27179789). Epiblast-specific knockout embryos exhibit multiple anomalies, including defective neural tube closure, underdeveloped brain, poorly developed myocardial trabeculae, which ultimately lead to embryonic lethality around 11.5 dpc (PubMed:27179789). DDX3X and DDX3Y double knockout is embryonic lethal (PubMed:30613052). DDX3X and DDX3Y double knockout germ cells can differentiate into spermatozoa (PubMed:30613052). Bone-marrow macrophage-specific knockout leads to a reduction in the expression of several cytokines, including IL1B, IL6, IL12 and IFNB1, in response to Listeria monocytogenes infection and pathogen-associated molecular patterns (PAMPs), including poly (I:C), poly (dA:dT) and LPS. This effect is more prononced in females than in male macrophages, probably due to the functional redundancy with DDX3Y gene located on chromosome Y (PubMed:30475900).|||In oocytes, expression levels increase from germinal vesicle immature oocytes to metaphase II (MII) and decline after fertilization in 1-cell and 2-cell embryos (at protein level) (PubMed:25050112). At 7.5 dpc, highly expressed in all embryonic cells and extraembryonic tissues, including ectoplacental cone, chorion, extraembryonic endoderm and parietal endoderm (at protein level) (PubMed:27179789). At 8.5-9.5 dpc, widely expressed (PubMed:8948440). At 8.5 dpc, levels decrease in extraembryonic tissues (PubMed:27179789). As development proceeds, expression becomes more restricted. At 11.5 dpc, most abundant in the neural tube, but still expressed at moderate levels in a number of other sites, including the mesenchyme of limbs and the face and in liver. At 14.5 dpc, highly expressed in the developing brain and caudal neural tube, but absent from the marginal layer of the neural tube. Also expressed in the developing metanephros and lung. At 15.5 dpc, expressed in the brain and spinal cord, as well as in teeth primordia, the lung and in the developing limb (PubMed:8948440). At 16.5 dpc, moderate, but non-uniform expression levels in the placenta (PubMed:27179789).|||Inflammasome|||Multifunctional ATP-dependent RNA helicase. The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity. In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs. Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA. Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities. Involved in transcription regulation. Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity. CDKN1A up-regulation may be cell-type specific. Binds CDH1/E-cadherin promoter and represses its transcription. Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis. May positively regulate TP53 transcription. Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC). Involved in the regulation of translation initiation. Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR). This function depends on helicase activity. Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning. Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety. Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process. Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle. May activate TP53 translation. Required for endoplasmic reticulum stress-induced ATF4 mRNA translation. Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E. Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E. Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta). Potentiate MAVS/RIGI-mediated induction of IFNB in early stages of infection (By similarity). Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:30475900). Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation. Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7. Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling. Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm. May also bind IFNB promoter; the function is independent of IRF3 (By similarity). Involved in both stress and inflammatory responses (PubMed:31511697). Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (By similarity). Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity. Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (PubMed:31511697). In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation. Cleavage by caspases may inactivate DDX3X and relieve the inhibition. Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant. ATPase and casein kinase-activating functions are mutually exclusive. May be involved in mitotic chromosome segregation (By similarity).|||Nucleus|||Phosphorylated by TBK1; the phosphorylation is required for the synergistic induction of IFNB mediated by TBK1 and DDX3X. Phosphorylated by IKBKE. Also phosphorylated by CSNK1E; this phosphorylation may inhibit RNA-stimulated ATPase activity.|||Stress granule|||The C-terminus (residues 536-662) is dispensable for DDX3X trafficking.|||The role of the nuclear export signal (NES) motif in XPO1-mediated DDX3X export is controversial (By similarity). In one study, NES has been found dispensable for DDX3X export while the helicase domain mediates the interaction with XPO1 (By similarity). However, in two other studies, DDX3X nuclear export is dependent on both NES and Ran in its GTP-bound form while the helicase domain is not required (By similarity).|||Upon stimulation of death receptors, including TNFRSF10B, recruited to receptors and cleaved by caspases. Proteolytic fragments remain associated with the receptors. This cleavage presumably inactivates DDX3X anti-apoptotic function.|||lamellipodium http://togogenome.org/gene/10090:Rtn2 ^@ http://purl.uniprot.org/uniprot/O70622|||http://purl.uniprot.org/uniprot/Q3TUZ6|||http://purl.uniprot.org/uniprot/Q6IM74|||http://purl.uniprot.org/uniprot/Q6IM75 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in skeletal and cardiac muscle (at protein level) (PubMed:19720795). Expressed predominantly in neural and muscular tissues (PubMed:9530622).|||Endoplasmic reticulum membrane|||Impaired exercise-induced SLC2A4/GLUT4 translocation to the cell membrane, impaired exercise-induced glucose uptake in skeletal muscle cells and impaired ability to reduce blood glucose levels on contraction/exercise.|||Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity (By similarity). Enhances trafficking of the glutamate transporter SLC1A1/EAAC1 from the endoplasmic reticulum to the cell surface (By similarity). Plays a role in the translocation of SLC2A4/GLUT4 from intracellular membranes to the cell membrane which facilitates the uptake of glucose into the cell (PubMed:19720795).|||Interacts with SPAST (By similarity). Interacts with BACE1 (By similarity). Interacts (via first transmembrane domain) with ARL6IP5/GTRAP3-18 (By similarity). Interacts (via N-terminus) with SLC1A1/EAAC1; the interaction promotes cell surface expression of SLC1A1 (By similarity).|||Membrane|||Sarcoplasmic reticulum membrane|||T-tubule|||Z line|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Prune2 ^@ http://purl.uniprot.org/uniprot/Q52KR3|||http://purl.uniprot.org/uniprot/Q8CA96 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PPase class C family. Prune subfamily.|||Cytoplasm|||Down-regulated after nerve growth factor (NGF)-induced differentiation, and up-regulated during the NGF-depletion-induced apoptosis.|||In the embryo specifically expressed in neural tube and neural crest-related tissues. At 10.5 dpc, highly expressed in neural tube and pharyngeal arches which are derived from neural crest. Expression is more restricted in the later stages of development. At 12.5 dpc, expressed in spinal cord, hindbrain, midbrain, forebrain and dorsal root ganglia (DRG). Although the expression at 14.5 dpc is similar to those in 12.5 dpc, the regions expressing in hindbrain, spinal cord and forebrain at 14.5 dpc are more dorsally restricted than at 12.5 dpc.|||May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. http://togogenome.org/gene/10090:Klrb1f ^@ http://purl.uniprot.org/uniprot/Q8VD98 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds CLEC2I/Clr-g leading to activation of natural killer cells or costimulation of IL-2 production and proliferation of T-cells in response to antigen stimulation. May contribute to the formation of the immunological synapse between T-cells and antigen-presenting dendritic cells.|||Highly expressed in dendritic cells. Detectable in natural killer cells.|||Membrane http://togogenome.org/gene/10090:Or56b2j ^@ http://purl.uniprot.org/uniprot/Q7TRP6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Patj ^@ http://purl.uniprot.org/uniprot/A2ADL9|||http://purl.uniprot.org/uniprot/Q63ZW7 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cytoplasm|||Expressed apically in the cortical neuroepithelium along the ventricular surface at 14.5 dpc.|||Expressed in the brain, high levels are detected in the cerebellum, inferior colliculus, vestibular nucleus, facial nucleus and thalamus (PubMed:9647694). Also detected in deep cerebellar nuclei, superior colliculus, dorsal transition zone, brain stem, as well as the glomerular and mitral cell layers of the olfactory bulb (PubMed:9647694). Within the cerebellum it is expressed in both Purkinje and granule cell layers (PubMed:9647694).|||Expressed in the kidney.|||Forms a ternary complex with PALS1 and CRB1 (By similarity). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, INADL/PATJ and PARD3/PAR3 (By similarity). Forms a heterotrimeric complex composed of MMP5, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (By similarity). Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via N-terminus) with PALS1/PALS (via PDZ domain) (PubMed:12527193, PubMed:20399730). Interacts with TJP3/ZO-3 and CLDN1/claudin-1 (By similarity). Interacts with ASIC3, KCNJ10, KCNJ15, GRIN2A, GRIN2B, GRIN2C, GRIN2D, NLGN2, and HTR2A (PubMed:9647694, PubMed:11872753, PubMed:14988405). Interacts with MPP7 (By similarity). Directly interacts with HTR4 (PubMed:15466885). Interacts (via PDZ domain 8) with WWC1 (via the ADDV motif) (By similarity). Interacts with SLC6A4 (PubMed:17452640). Interacts (via C-terminus) with ARHGEF18 (By similarity). Interacts with NPHP1 (By similarity). Interacts with PARD3/PAR3 (By similarity).|||Interacts with NRXN2.|||Scaffolding protein that facilitates the localization of proteins to the cell membrane (PubMed:11872753). Required for the correct formation of tight junctions and epithelial apico-basal polarity (By similarity). Positively regulates epithelial cell microtubule elongation and cell migration, possibly via facilitating localization of PRKCI/aPKC and PAR3D/PAR3 at the leading edge of migrating cells (By similarity). Plays a role in the correct reorientation of the microtubule-organizing center during epithelial migration (By similarity). May regulate the surface expression and/or function of ASIC3 in sensory neurons (PubMed:11872753). May recruit ARHGEF18 to apical cell-cell boundaries (By similarity).|||The L27 domain (also called Maguk recruitment domain) is required for interaction with PALS1 and CRB3, and PALS1 localization to tight junctions.|||The PDZ domain 6 mediates interaction with the C-terminus of TJP3 and is crucial for localization to the tight junctions. The PDZ domain 8 interacts with CLDN1 but is not required for proper localization (By similarity). The PDZ domain 2 of isoform 3 mediates interactions with KCNJ10, KCNJ15, GRIN2B and NLGN2. The PDZ domain 3 of isoform 3 mediates interactions with KCNJ15, GRIN2A, GRIN2B, GRIN2C, GRIN2D and NRXN2. The PDZ domain 4 of isoform 3 mediates interaction with ASIC3.|||perinuclear region|||tight junction http://togogenome.org/gene/10090:Sfmbt1 ^@ http://purl.uniprot.org/uniprot/Q3TUT9|||http://purl.uniprot.org/uniprot/Q9JMD1 ^@ Developmental Stage|||Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contaminating sequence. Potential poly-A sequence.|||Highly expressed in the testis, low expression is detected in brain, kidney, heart and lung. Highly expressed in germ cells, where it associates with the synaptic regions of meiotic chromosomes in pachytene stage spermatocytes.|||Highly expressed in undifferentiated myoblasts and expression is reduced during the course of differentiation.|||Histone-binding protein, which is part of various corepressor complexes. Mediates the recruitment of corepressor complexes to target genes, followed by chromatin compaction and repression of transcription. Plays a role during myogenesis: required for the maintenance of undifferentiated states of myogenic progenitor cells via interaction with MYOD1. Interaction with MYOD1 leads to the recruitment of associated corepressors and silencing of MYOD1 target genes. Part of the SLC complex in germ cells, where it may play a role during spermatogenesis.|||Interacts with MYOD1 (By similarity). Component of the SLC (SFMBT1-LSD1-CoREST) corepressor complex, which also contains KDM1A/LSD1 and RCOR1/CoREST. Interacts with KDM1A/LSD1 and RCOR1/CoREST (By similarity). Interacts with MYOD1. Interacts with L3MBTL3 (PubMed:30442713).|||Nucleus|||The MBT repeats mediate binding to histones tails; however, in contrast to other MBT repeats, does not bind specific histone lysine modifications. The MBT repeats lack the conserved Asp and aromatic cage at conserved positions (By similarity). http://togogenome.org/gene/10090:Dcaf6 ^@ http://purl.uniprot.org/uniprot/Q9DC22 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with the nuclear receptors NR3C1 and AR in the presence of ligand. Interacts with DDB1, CUL4A and CUL4B (By similarity).|||Ligand-dependent coactivator of nuclear receptors. Enhance transcriptional activity of the nuclear receptors NR3C1 and AR. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex (By similarity).|||Nucleus http://togogenome.org/gene/10090:Trim17 ^@ http://purl.uniprot.org/uniprot/Q7TPM3 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Almost exclusively in the testis.|||Auto-ubiquitinated.|||Belongs to the TRIM/RBCC family.|||By NFATC3 and JUN cooperation during neuronal apoptosis.|||Cytoplasm|||E3 ubiquitin ligase that plays important roles in the regulation of neuronal apoptosis, selective autophagy or cell proliferation (PubMed:20559321, PubMed:22976837, PubMed:25215946). Stimulates the degradation of kinetochore ZW10 interacting protein ZWINT in a proteasome-dependent manner, leading to negative regulation of cell proliferation. Inhibits autophagic degradation of diverse known targets while contributing to autophagy of midbodies. Autophagy-inhibitory activity involves MCL1, which TRIM17 assembles into complexes with the key autophagy regulator BECN1 (By similarity). Controls neuronal apoptosis by mediating ubiquitination and degradation of MCL1 to initiate neuronal death (PubMed:22976837). In addition, regulates NFAT transcription factors NFATC3 and NFATC4 activities by preventing their nuclear localization, thus inhibiting their transcriptional activities (PubMed:25215946). Decreases TRIM41-mediated degradation of ZSCAN2 thereby stimulating alpha-synuclein/SNCA transcription in neuronal cells (PubMed:30485814). Prevents the E3 ubiquitin-ligase activity of TRIM28 and its interaction with anti-apoptotic BCL2A1, blocking TRIM28 from ubiquitinating BCL2A1 (By similarity).|||Interacts (via coiled coil) with TRIM44 (via coiled coil). Interacts with TRIM28; this interaction prevents TRIM28 activity on BCL2A1 (By similarity). Interacts with TRIM41; this interaction prevents TRIM41 activity on ZSCAN2 (By similarity). Interacts with BECN1 (By similarity). Interacts with NFATC3 and NFATC4; these interactions prevent NFATC3 and NFATC4 nuclear localization (PubMed:25215946).|||Lysosome http://togogenome.org/gene/10090:Myf5 ^@ http://purl.uniprot.org/uniprot/A2RSK4|||http://purl.uniprot.org/uniprot/P24699 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYOG and MYOD1, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.|||Efficient DNA binding requires dimerization with another bHLH protein.|||Induces fibroblasts to differentiate into myoblasts. Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.|||Nucleus http://togogenome.org/gene/10090:Sult2a1 ^@ http://purl.uniprot.org/uniprot/P52843 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Cytoplasm|||Highly expressed in liver.|||Homodimer.|||Not expressed until 19 dpc.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands (PubMed:12639899). Mediates the sulfation of a wide range of steroids and sterols, including pregnenolone, androsterone, DHEA, bile acids, cholesterol and as well many xenobiotics that contain alcohol and phenol functional groups. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Plays an important role in maintening steroid and lipid homeostasis. Plays a key role in bile acid metabolism (By similarity). In addition, catalyzes the metabolic activation of potent carcinogenic polycyclic arylmethanols (By similarity). http://togogenome.org/gene/10090:Pramel1 ^@ http://purl.uniprot.org/uniprot/Q99MW3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PRAME family.|||Cytoplasm|||Expressed in the spermatogenic cells during early spermatogenesis (at protein level). Expressed postnatally from week 1 onwards with a slight increase in expression levels until week 3 (at protein level).|||May play a role in acrosome development and also in sperm maturation and motility.|||Specifically expressed in testis (at protein level).|||acrosome|||flagellum http://togogenome.org/gene/10090:Npas2 ^@ http://purl.uniprot.org/uniprot/P97460 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Carbon monoxide (CO) and the redox state of the cell can modulate the transcriptional activity of the NPAS2-BMAL1 heterodimer. NADH and NADPH enhance the DNA-binding activity of the heterodimer whereas CO binds the heme group in NPAS2 and inhibits the DNA-binding activity of the heterodimer.|||Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with NCOA3, KAT2B and CREBBP (By similarity). Forms a heterodimer with BMAL1 and this heterodimerization is required for E-box-dependent transactivation. Interacts with EP300.|||Expressed in the retinal ganglion cells (at protein level). Expressed in the hypothalamic suprachiasmatic nuclei (SCN) of the brain. Also found in spinal cord, and to a lesser extent in colon, small intestine and uterus. Exhibits a diurnal variation in its expression in the brain (PubMed:29163035).|||Expression in the retinal ganglion cells and heart oscillates in a circadian manner.|||First detected 3 days after birth.|||Mice exhibit altered sleep and locomotor activity. Show alterations in sleep homeostasis, altering the electrophysiological properties of neurons after sleep deprivation. Display normal patterns of sleep throughout the light period, however during the active, nocturnal period, they remain awake nearly continuously for the first 8 to 9 hours of darkness and tend to fast rather than readapt to eating in daylight. Exhibit a dysregulation in the lipid and fatty acid metabolism pathways and a significant reduction in daytime contrast sensitivity. Null mutant mice and the mice with a conditional knockdown in the ventral striatum show a reduced anxiety-like behavior and a reduced sensitivity to diazepam (PubMed:29163035).|||Nucleus|||Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. NPAS2 plays an important role in sleep homeostasis and in maintaining circadian behaviors in normal light/dark and feeding conditions and in the effective synchronization of feeding behavior with scheduled food availability. Regulates the gene transcription of key metabolic pathways in the liver and is involved in DNA damage response by regulating several cell cycle and DNA repair genes. Controls the circadian rhythm of NR0B2 expression by binding rhythmically to its promoter (PubMed:25212631). Mediates the diurnal variation in the expression of GABARA1 receptor in the brain and contributes to the regulation of anxiety-like behaviors and GABAergic neurotransmission in the ventral striatum (PubMed:29163035). http://togogenome.org/gene/10090:Vmn1r81 ^@ http://purl.uniprot.org/uniprot/Q8R286 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Klk1b27 ^@ http://purl.uniprot.org/uniprot/Q9JM71 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Detectable in testis 4 weeks after birth, becoming more prominent thereafter.|||Expressed in testis and submaxillary gland. Not expressed in heart, brain, spleen, lung, liver, muscle, kidney and ovary. In the testis, expression localized specifically to Leydig cells in the interstitial tissues.|||Serine protease with chymotrypsin-like cleavage specificity. Shows activity towards casein, gelatin, IGFBP3 and fibronectin but not towards laminin or collagens I and IV. Does not hydrolyze kininogin to release Lys-bradykinin.|||Strongly inhibited by protease inhibitors diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride and SBTI. http://togogenome.org/gene/10090:Septin4 ^@ http://purl.uniprot.org/uniprot/A0A5F8MP96|||http://purl.uniprot.org/uniprot/P28661 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Expressed in LGR5-positive intestinal stem cells and lysozyme-positive Paneth cells (at protein level) (PubMed:30389919). Expressed in the brain and testis (PubMed:15737931).|||Expressed in the cerebral cortex, striatum, midbrain, cerebellum and spinal cord (at protein level). Expressed in the substantia nigra pars compacta, ventral tegmental area, projection fiber bundles and in axon terminals surrounding striatal neurons (at protein level) (PubMed:17296554). Expressed in hair follicle stem cells (at protein level) (PubMed:23788729). Expressed in small intestinal crypts; abundantly expressed at the crypt base (at protein level) (PubMed:30389919). Widely expressed in the brain and to a lesser extent in the testis, lung and liver (PubMed:21679490, PubMed:17296554).|||Expressed in the intermediate zone and cortical plate of the cortex at 15.5 dpc.|||Filament-forming cytoskeletal GTPase (Probable). Pro-apoptotic protein involved in LGR5-positive intestinal stem cell and Paneth cell expansion in the intestines, via its interaction with XIAP (PubMed:30389919). May also play a role in the regulation of cell fate in the intestine (PubMed:30389919). Positive regulator of apoptosis involved in hematopoietic stem cell homeostasis; via its interaction with XIAP (PubMed:20952537). Negative regulator of repair and hair follicle regeneration in response to injury, due to inhibition of hair follicle stem cell proliferation, potentially via its interaction with XIAP (PubMed:23788729). Plays an important role in male fertility and sperm motility (PubMed:15737930, PubMed:15737931). During spermiogenesis, essential for the establishment of the annulus (a fibrous ring structure connecting the midpiece and the principal piece of the sperm flagellum) which is a requisite for the structural and mechanical integrity of the sperm (PubMed:15737930, PubMed:15737931). Involved in the migration of cortical neurons and the formation of neuron leading processes during embryonic development (PubMed:20181826). Required for dopaminergic metabolism in presynaptic autoreceptors; potentially via activity as a presynaptic scaffold protein (PubMed:17296554).|||Highly expressed in the brain and testis and, to a lesser extent in the heart, lung and kidney (PubMed:12106288, PubMed:12581152, PubMed:15737931). In the brain, abundant in areas of high cell density, particularly in the stria terminalis (PubMed:12106288). Expressed in the entorhinal, temporal and visual cortices and the hippocampus of the brain where is colocalizes with DYRK1A in postnatal day 1 and adult mice. Expressed and extensively colocalizes with DYRK1A in apical dendrites of pyramidal cells (PubMed:18938227).|||Induced by S.japonicum egg-mediated liver fibrosis at the site of egg granulomas; expression peaks at 12 weeks post infection with expression decreasing thereafter.|||Interacts with DPYSL5.|||Knockout mice have a decreased basal prepulse startle response and an enhanced acoustic startle response (PubMed:17296554). Decreased concentration of TH and SLC6A3/DAT in dopaminergic axons and axon terminals, does not affect axon morphology (PubMed:17296554). Male mice are sterile due to immotile and structurally defective sperm (PubMed:15737930, PubMed:15737931). Sperms exhibit defective mitochondrial architecture, bent and nonmotile tails, absence of the annulus (a fibrous ring structure connecting the midpiece and the principal piece of the sperm flagellum), lower ATP consumption, impaired capacitation and defects in the removal of residual cytoplasm (PubMed:15737930, PubMed:15737931). Increased in intestinal crypt diameter, length and cell number (PubMed:30389919). Decreased apoptosis and increased maintenance of colon crypt architecture in response to intestinal barrier damage, as a result of improved Lgr5-positive intestinal stem cell-mediated regeneration (PubMed:30389919). Decrease in differentiated intestinal goblet cells (PubMed:30389919). Increase proliferation of Lgr5-positive intestinal stem cells and lysozyme-positive granular Paneth cells in the crypt base of both the small and large intestines (PubMed:30389919). Increase in Reg4-positive cells in colon epithelium and nuclear localization of CTNNB1 in cells of the intestinal crypt base (PubMed:30389919). Increased incidence of spontaneous hematopoietic malignancies, splenomegaly and a third of mice developed spontaneous neoplasia at 11 to 15 months old (PubMed:20952537). Increased number of B-linage progenitors, immature B cells and increased functional hematopoietic progenitor cells in the bone marrow of 6 to 13 week old mice, increased hematopoietic progenitor cell levels persisted in 11 to 15 month old mice (PubMed:20952537). Normal hair follicle bulge morphology but twice as many epithelial progenitor cells and an elongated tail epithelial strand (PubMed:23788729). Significantly improved dorsal skin wound repair which included an increased amount of proliferating hair follicle stem cells in the wound bed (PubMed:23788729). Decrease in apoptosis of hematopoietic progenitors in response to irradiation (PubMed:20952537). SEPTIN4 and XIAP double knockout mice show no differences in apoptosis or lymphoproliferation in hematopoietic stem and progenitor cells (PubMed:20952537). Delayed dermal wound repair and hair follicle regeneration, via increased apoptosis of hair follicle stem cells (PubMed:23788729).|||May act as a tumor suppressor in both hematopoietic and neoplastic malignancies.|||May be phosphorylated.|||Mitochondrion|||Perikaryon|||Phosphorylated by DYRK1A.|||Predominantly expressed in embryonic brain and dorsal root ganglion neurons.|||Predominantly expressed in the brain at 14 dpc and on postnatal day 1.|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Interacts with SEPTIN8 (By similarity). Component of a septin core octameric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 (By similarity). Interacts with SEPTIN14 (via C-terminus) (PubMed:20181826). Interacts with DYRK1A (PubMed:18938227). Interacts with SLC6A3/DAT and SNCA/alpha-synuclein (PubMed:17296554). Interacts with STX1A; in the striatum (PubMed:17296554). Interacts with XIAP (via BIR3 domain) following the induction of apoptosis (PubMed:30389919). Interacts with AREL1 (via HECT domain); in the cytoplasm following induction of apoptosis (PubMed:23479728).|||Synapse|||Ubiquitinated by AREL1.|||Widely expressed in embryos at 7 dpc.|||axon|||cytosol|||dendrite|||flagellum|||secretory vesicle http://togogenome.org/gene/10090:Pdp2 ^@ http://purl.uniprot.org/uniprot/Q504M2 ^@ Similarity ^@ Belongs to the PP2C family. http://togogenome.org/gene/10090:Snrnp25 ^@ http://purl.uniprot.org/uniprot/Q8VIK1 ^@ Subcellular Location Annotation|||Subunit ^@ Component of the U11/U12 snRNPs that are part of the U12-type spliceosome.|||Nucleus http://togogenome.org/gene/10090:Katnb1 ^@ http://purl.uniprot.org/uniprot/Q8BG40 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat KATNB1 family.|||Cytoplasm|||Homozygous loss of the gene is embryonic lethal. Mutant animals have dramatically reduced body size, reduced limb bud outgrowth, microphthalmia to anophthalmia and forebrain abnormalities ranging from microcephaly to holoprosencephaly. Brains of mutant mice have reduced cycling and proliferating radial neuroepithelial progenitor cells compared to wild-type, with a more profound loss of cells that depend upon asymmetrical cell divisions. These cells also show evidence of increased apoptosis.|||Interacts with KATNA1. This interaction enhances the microtubule binding and severing activity of KATNA1 and also targets this activity to the centrosome (PubMed:16203747). This interaction is weakly competed by KATNBL1 which has a lower affinity for it (By similarity). Interacts with ASPM; the katanin complex formation KATNA1:KATNB1 is required for the association of ASPM (PubMed:28436967). Interacts with dynein, microtubules, NDEL1 and PAFAH1B1 (PubMed:16203747). Interacts with KATNAL1; this interaction is weakly competed by KATNBL1 which has a lower affinity for it (By similarity). Interacts with CAMSAP2 and CAMSAP3; leading to regulate the length of CAMSAP-decorated microtubule stretches (By similarity).|||Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. The function in regulating microtubule dynamics at spindle poles seems to depend on the association of the katanin KATNA1:KATNB1 complex with ASPM which recruits it to microtubules. Reversely KATNA1:KATNB1 can enhance ASPM blocking activity on microtubule minus-end growth. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth.|||centrosome|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Csrp3 ^@ http://purl.uniprot.org/uniprot/P50462 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||LIM zinc-binding domain 1 is required for self-association. LIM zinc-binding domain 1 and LIM zinc-binding domain 2 both are required for optimal actin-bundling activity. LIM zinc-binding domain 1 mediates binding to MYOD1. LIM zinc-binding domain 2 mediates binding to SPTB.|||Mutant mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Ultrastructural analysis revealed a dramatic disruption of cardiomyocyte cytoarchitecture. At birth, these hearts are not hypertrophic, but already abnormally soft, with cell-autonomous and Csrp3-sensitive alterations in cytoarchitecture. The morphological, functional, and molecular features of the cardiac phenotype in mutant adult mice are undistinguishable from those seen in human heart failure resulting from dilated cardiomyopathy of various etiolologies, these mice can thus be used as model. Heterozygous mice display a more pronounced left ventricular dilation and systolic dysfunction and decreased survival after myocardial infarction.|||Nucleus|||Phosphorylated by PKC/PRKCA.|||Positive regulator of myogenesis. Acts as cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (PubMed:9039266, PubMed:15665106). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly. Proposed to contribute to the maintenance of muscle cell integrity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (By similarity). In vitro can inhibit PKC/PRKCA activity. Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (PubMed:27353086).|||Self-associates. Oligomeric in the cytoplasm and monomeric in the nucleus. Homooligomers preferentially form along the actin cytoskeleton (By similarity). Interacts with TCAP (PubMed:20044516). Interacts with LDHD, MYOD1, MYOG, ACTN2, NRAP, MYF6 (By similarity). Interacts (via N-terminus)D with GLRX3 (via C-terminus) and PPP3CA; GLRX3 and calcineurin compete for interaction with CSRP3 (PubMed:18258855). Interacts with CFL2; the stoichiometry influences F-actin depolymerization and possibly two molecules of CFL2 can interact with one molecule of CSRP3 resulting in the highest functional impact; the interaction is stronger with phosphorylated CFL2 (By similarity).|||Z line|||cytoskeleton|||sarcomere http://togogenome.org/gene/10090:Dkkl1 ^@ http://purl.uniprot.org/uniprot/A0A1B0GRV4|||http://purl.uniprot.org/uniprot/Q3V2N2|||http://purl.uniprot.org/uniprot/Q9QZL9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains a N-terminal domain similar to that of the N-terminal section of DKK3.|||Expressed in the embryo only after day 15. In the adult, expressed only in developing spermatocytes. Expressed in the developing cochlea. Detected only in developing spermatocytes and spermatids in seminiferous tubules. Moreover, first appears specifically in zygotene/pachytene spermatocytes. Found in puddles in the pachytene spermatocytes of all stage tubules and then in crescent shaped structures characteristic of acrosomes in early step spermatids. Detected in mature sperm (PubMed:15892050). Expressed strongly in trophoblast stem cells and further up-regulated in trophoblast giant cells. Expression is maintained in post-implantation placental tissues in utero. Highly expressed from 7.5 dpc trophectoderm to 12.5 dpc placenta. Expression remains baseline in postimplantation embryonic tissues (PubMed:19596312).|||Interacts with SLXL1; Co-localize in seminiferous tubules (PubMed:21698294). Interacts with SLY (PubMed:19176879).|||Involved in fertilization by facilitating sperm penetration of the zona pellucida (PubMed:19596312, PubMed:22817830). May promote spermatocyte apoptosis, thereby limiting sperm production. In adults, may reduce testosterone synthesis in Leydig cells (PubMed:18818293). Is not essential either for development or fertility (PubMed:19596310).|||N-glycosylated during spermatogenesis. Not N-glycosylated in mature sperm.|||Nullizygous embryos Dkkl1 mice develop into viable, fertile adults.|||Secreted|||Testis-specific. Abundant in the seminiferous tubules where it is associated with developing spermatocytes. Expressed only in testis (at protein level) (PubMed:15892050, PubMed:19596310). Not detectable on postnatal days 4 and 9 but after day 18 it gradually increased as the development of testes progressed. Expressed at high levels in testis and at weak levels in epididymis (PubMed:22817830).|||acrosome http://togogenome.org/gene/10090:Adamts8 ^@ http://purl.uniprot.org/uniprot/F8VQ15 ^@ Caution|||Cofactor|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular matrix http://togogenome.org/gene/10090:Jtb ^@ http://purl.uniprot.org/uniprot/O88824 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JTB family.|||Cytoplasm|||Interacts with AURKA, AURKB, BIRC5 and INCENP. May be a component of the CPC at least composed of BIRC5/survivin, CDCA8/borealin, INCENP and AURKB/Aurora-B (By similarity).|||Membrane|||Mitochondrion|||Required for normal cytokinesis during mitosis. Plays a role in the regulation of cell proliferation. May be a component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Increases AURKB activity (By similarity). Inhibits apoptosis induced by TGFB1. Overexpression induces swelling of mitochondria and reduces mitochondrial membrane potential.|||Undergoes N-terminal proteolytic processing, removing a peptide of about 1 kDa from the N-terminus of the protein.|||Up-regulated by TGFB1 in mammary epithelial cells.|||centrosome|||spindle http://togogenome.org/gene/10090:Psip1 ^@ http://purl.uniprot.org/uniprot/Q99JF8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HDGF family.|||Citrullinated by PADI4.|||Monomer (By similarity). Interacts with IFRD1/PC4 (By similarity). Interacts (via IBD domain) with POGZ (via IBM motif) and CDCA7L (via IBM motifs) (By similarity). Interacts (via IBD domain) with KMT2A (via IBM motifs) with a moderate affinity whereas interacts with the KMT2A-MEN1 complex with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (By similarity). Interacts (via IBD domain) with IWS1 (via IBM motif), MED1 (via IBM motif) and DBF4 (via IBM motifs) (By similarity).|||Nucleus|||Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis (By similarity). http://togogenome.org/gene/10090:Pip4k2b ^@ http://purl.uniprot.org/uniprot/Q80XI4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Homodimer. Binds TNFRSF1A. Interacts with PIP4K2A; the interaction suppresses ubiquitination by the SPOP/CUL3 complex (By similarity). Probably interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase activity (By similarity).|||Nucleus|||Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration. Its GTP-sensing activity is critical for metabolic adaptation. In collaboration with PIP4K2A, has a role in mediating autophagy in times of nutrient stress (PubMed:29727621). Required for autophagosome-lysosome fusion and the regulation of cellular lipid metabolism (PubMed:29727621). PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (By similarity).|||Phosphorylated on serine residues.|||Ubiquitinated by the SPOP/CUL3 complex. Ubiquitination is stimulated by PtdIns5P levels. http://togogenome.org/gene/10090:Ska2 ^@ http://purl.uniprot.org/uniprot/Q9CR46 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKA2 family.|||Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. In the complex, it is required for SKA1 localization. Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules.|||Component of the SKA1 complex, composed of SKA1, SKA2 and SKA3. Forms a heterodimer with SKA1; the heterodimer interacting with SKA3. The core SKA1 complex is composed of 2 SKA1-SKA2 heterodimers, each heterodimer interacting with a molecule of the SKA3 homodimer. The core SKA1 complex associates with microtubules and forms oligomeric assemblies. Interacts directly with SKA1. Binds directly to microtubules; but with a much lower affinity than SKA1 in vivo (By similarity).|||kinetochore|||spindle http://togogenome.org/gene/10090:Gabrg3 ^@ http://purl.uniprot.org/uniprot/P27681 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG3 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.|||May be palmitoylated.|||Postsynaptic cell membrane|||This subunit carries the benzodiazepine binding site. http://togogenome.org/gene/10090:Vsig2 ^@ http://purl.uniprot.org/uniprot/Q9Z109 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the stomach, colon and prostate.|||Membrane http://togogenome.org/gene/10090:L1td1 ^@ http://purl.uniprot.org/uniprot/Q587J6 ^@ Similarity ^@ Belongs to the transposase 22 family. http://togogenome.org/gene/10090:Dhdh ^@ http://purl.uniprot.org/uniprot/Q9DBB8 ^@ Similarity|||Subunit ^@ Belongs to the Gfo/Idh/MocA family.|||Homodimer. http://togogenome.org/gene/10090:Dusp3 ^@ http://purl.uniprot.org/uniprot/Q9D7X3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Interacts with VRK3, which seems to activate it's phosphatase activity.|||Nucleus|||Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2 (By similarity). http://togogenome.org/gene/10090:Inhca ^@ http://purl.uniprot.org/uniprot/Q9DBD0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transferrin family.|||Detected in blood plasma, heart, kidney, liver, colon, lung, spleen, pancreas and testis (at protein level).|||Inhibitor for carbonic anhydrase 2 (CA2) (By similarity). Does not bind iron ions (PubMed:17511619, PubMed:18712936).|||Monomer (PubMed:20572014). Interacts (via transferrin-like domain 2) with CA2 (PubMed:18712936).|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Or13p8 ^@ http://purl.uniprot.org/uniprot/Q3KPC7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pafah2 ^@ http://purl.uniprot.org/uniprot/Q8VDG7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the serine esterase family.|||Catalyzes the hydrolyze of the acetyl group at the sn-2 position of platelet-activating factor (PAF) and its analogs, leading to their inactivation (By similarity). Hydrolyzes propionyl and butyroyl moieties approximately half as effectively as PAF (By similarity). Also catalyzes transacetylation of the acetyl group from platelet-activating factor (PAF) to lysoplasmalogen and to sphingosine, producing plasmalogen analogs of PAF and N-acetylsphingosine (C2-ceramide) respectively. Has a marked selectivity for phospholipids with short acyl chains at the sn-2 position (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Membrane|||Monomer. http://togogenome.org/gene/10090:Or2a57 ^@ http://purl.uniprot.org/uniprot/Q8VF18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mfap1a ^@ http://purl.uniprot.org/uniprot/C0HKD8|||http://purl.uniprot.org/uniprot/C0HKD9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MFAP1 family.|||Component of the spliceosome B complex. Interacts with PRPF38A (via N-terminal interaction domain).|||Involved in pre-mRNA splicing as a component of the spliceosome.|||Nucleus http://togogenome.org/gene/10090:Zbtb7b ^@ http://purl.uniprot.org/uniprot/Q64321 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated directly and specifically by EP300. EP300-mediated acetylation of Lys-210, Lys-216 and Lys-339 stabilizes the protein by antagonizing ubiquitin conjugation.|||Chimeric cDNA.|||Defects in Zbtb7b are the cause of helper deficient disease (HD) or helpless disease. HD and helpless mice are distinguished by the virtual absence of peripheral T-cells of the CD4(+)CD8(-) major histocompatibility complex (MHC) class II-restricted T-helper subset due to a specific block in thymic development. The developmental defect is selective for CD4(+)CD8(-) cells; the maturation of CD4(-)CD8(+) and gamma delta T-cells is normal indicating that lineage commitment is specifically perturbed without affecting positive selection. In helpless disease, NKT cells are hyperproliferative, most lack CD4 and instead express CD8. The majority of NKT cells in the thymus produce IL17 with high frequency while very few produce IFNG or other cytokines (PubMed:23105140).|||Expressed, beginning at 9.5 days of gestation and at 10.5 days in regions destined to become skin. In adult animals, expression is predominantly in skin (PubMed:7937772). Expression is significantly increased during brown adipocyte differentiation (PubMed:28784777).|||Expression in mammary glands is induced by insulin.|||Homodimerizes (PubMed:22730529). Interacts with NCL, NEDD4 and YBX1 (PubMed:28784777). Interacts with HNRNPU (via RNA-binding RGG-box region); the interaction facilitates the recruitment of long non-coding RNA Blnc1 by ZBTB7B (PubMed:28784777). Interacts with HDAC4 and HDAC5; the interaction allows the recruitment of HDAC4 and HDAC5 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression (PubMed:22730529).|||Mutant females are unable to efficiently secrete milk lipid and to nurse the offspring. They show normal mammary gland morphogenesis in puberty and alveologenesis in pregnancy, but are defective in triggering the onset of lactation upon parturition with large cellular lipid droplets retained within alveolar epithelial cells (PubMed:29420538). Mice are more sensitive to cold temperature, with impaired cold-induced transcriptional remodeling in brown fat and diminished browning of inguinal white fat (PubMed:28784777).|||Nucleus|||Transcription regulator that acts as a key regulator of lineage commitment of immature T-cell precursors. Exerts distinct biological functions in the mammary epithelial cells and T cells in a tissue-specific manner (PubMed:15729333, PubMed:29420538). Necessary and sufficient for commitment of CD4 lineage, while its absence causes CD8 commitment. Development of immature T-cell precursors (thymocytes) to either the CD4 helper or CD8 killer T-cell lineages correlates precisely with their T-cell receptor specificity for major histocompatibility complex class II or class I molecules, respectively. Cross-antagonism between ZBTB7B and CBF complexes are determinative to CD4 versus CD8 cell fate decision (PubMed:15729333, PubMed:24880459, PubMed:18258917, PubMed:23481257). Suppresses RUNX3 expression and imposes CD4+ lineage fate by inducing the SOCS suppressors of cytokine signaling. induces, as a transcriptional activator, SOCS genes expression which represses RUNX3 expression and promotes the CD4+ lineage fate (PubMed:24880459). During CD4 lineage commitment, associates with multiple sites at the CD8 locus, acting as a negative regulator of the CD8 promoter and enhancers by epigenetic silencing through the recruitment of class II histone deacetylases, such as HDAC4 and HDAC5, to these loci (PubMed:22730529). Regulates the development of IL17-producing CD1d-restricted naural killer (NK) T cells (PubMed:23105140). Also functions as an important metabolic regulator in the lactating mammary glands. Critical feed-forward regulator of insulin signaling in mammary gland lactation, directly regulates expression of insulin receptor substrate-1 (IRS-1) and insulin-induced Akt-mTOR-SREBP signaling (PubMed:29420538). Transcriptional repressor of the collagen COL1A1 and COL1A2 genes. May also function as a repressor of fibronectin and possibly other extracellular matrix genes (PubMed:7937772). Potent driver of brown fat development, thermogenesis and cold-induced beige fat formation (PubMed:28784777). Recruits the brown fat lncRNA 1 (Blnc1):HNRNPU ribonucleoprotein complex to activate thermogenic gene expression in brown and beige adipocytes (PubMed:28784777).|||Ubiquitinated, leading to proteasomal degradation. Competes with acetylation on Lys-210, Lys-216 and Lys-339.|||Widely expressed, with a higher level in skin. Expressed in thymus. Restricted to CD4 cells (mature single positive CD4(+) and intermediate CD4(+)CD8(+) cells). Expressed in the luminal epithelial cells in the mammary glands where is up-regulated at late pregnancy and lactation (PubMed:29420538). Expression is enriched in brown fat (PubMed:28784777). http://togogenome.org/gene/10090:St3gal3 ^@ http://purl.uniprot.org/uniprot/P97325|||http://purl.uniprot.org/uniprot/Q3UWD5|||http://purl.uniprot.org/uniprot/Q9CZ48|||http://purl.uniprot.org/uniprot/Q9DBB6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Catalyzes the formation of the NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc-, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc- and NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc- sequences found in terminal carbohydrate groups of glycoproteins and glycolipids. The highest activity is toward Gal-beta-1,3-GlcNAc and the lowest toward Gal-beta-1,3-GalNAc.|||Developmental regulation only occurs in liver, heart, kidney and spleen.|||Found in all tissues tested. High expression found in brain, liver, kidney, colon, heart and spleen.|||Golgi stack membrane|||Membrane http://togogenome.org/gene/10090:Galnt7 ^@ http://purl.uniprot.org/uniprot/Q80VA0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Glycopeptide transferase involved in O-linked oligosaccharide biosynthesis, which catalyzes the transfer of an N-acetyl-D-galactosamine residue to an already glycosylated peptide. In contrast to other proteins of the family, it does not act as a peptide transferase that transfers GalNAc onto serine or threonine residue on the protein receptor, but instead requires the prior addition of a GalNAc on a peptide before adding additional GalNAc moieties. Some peptide transferase activity is however not excluded, considering that its appropriate peptide substrate may remain unidentified (By similarity).|||Golgi apparatus membrane|||Highly expressed in sublingual gland. Expressed at lower level in stomach, small intestiine and colon.|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Slamf8 ^@ http://purl.uniprot.org/uniprot/Q9D3G2 ^@ Function|||Subcellular Location Annotation ^@ May play a role in B-lineage commitment and/or modulation of signaling through the B-cell receptor.|||Membrane http://togogenome.org/gene/10090:Dctn2 ^@ http://purl.uniprot.org/uniprot/Q3TPZ5|||http://purl.uniprot.org/uniprot/Q99KJ8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynactin subunit 2 family.|||Membrane|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (PubMed:14983524).|||Present at high levels in both cytoplasmic and membrane-associated forms in neonates. Levels of membrane-associated form are greatly reduced in the adult.|||Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters and consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with BICD2 and CEP135 (PubMed:11483508, PubMed:14983524, PubMed:22956769). Interacts with DYNAP. Interacts with ECPAS. Interacts with MAPRE1 (By similarity).|||centrosome http://togogenome.org/gene/10090:Zfp354a ^@ http://purl.uniprot.org/uniprot/Q61751 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Highly expressed in eye and kidney. Detected at high levels in adult brain and kidney, and at lower levels in adult liver, lung, skeletal muscle, heart, salivary gland, testis and tongue. Detected in embryonic brain, heart, lung,kidney and gut.|||It may play a role in renal development and may also be involved in the repair of the kidney after ischemia-reperfusion or folic acid administration.|||Nucleus http://togogenome.org/gene/10090:Strbp ^@ http://purl.uniprot.org/uniprot/Q91WM1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain at 13.5 dpc. Expressed in brain, trigeminal ganglia and nasal epithelium at 18.5 dpc.|||Interacts with EIF2AK2 (By similarity). Associates with microtubules; it is unsure whether such interaction is direct or indirect.|||Involved in spermatogenesis and sperm function. Plays a role in regulation of cell growth (By similarity). Binds to double-stranded DNA and RNA (By similarity). Binds most efficiently to poly(I:C) RNA than to poly(dI:dC) DNA (By similarity). Binds also to single-stranded poly(G) RNA (By similarity). Binds non-specifically to the mRNA PRM1 3'-UTR and adenovirus VA RNA.|||Isoform 2 is expressed in spermatocytes (at protein level). Expressed in testis, thymus, ovary, liver, kidney, heart, spleen and brain. Expressed in cortex, dentate gyrus and Purkinje cell layer and granule cells of the cerebellum.|||cytoskeleton http://togogenome.org/gene/10090:Atat1 ^@ http://purl.uniprot.org/uniprot/Q8K341 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoacetylation strongly increases tubulin acetylation.|||Belongs to the acetyltransferase ATAT1 family.|||Component of the BBSome complex (By similarity). Interacts with AP2 alpha-adaptins, including AP2A2, but not with AP1 gamma-adaptin (AP1G1/AP1G2); this interaction is required for efficient alpha-tubulin acetylation, hence clathrin-coated pits are sites of microtubule acetylation.|||Cytoplasm|||Mutant mice are viable and show no overt phenotype. Drastic loss of tubulin acetylation in all tissues anlyzed, including in early embryos. In dorsal hippocampus, but not in ventral hippocampus, the dentate gyrus is slightly deformed, showing a prominent bulge in the lateral blade of the granular cell layers. In addition, the lateral ventricle appears to be dilated (PubMed:23720746). Homozygous mutant males exhibit decreased fertility (PubMed:23748901). Mature spermatozoa from cauda epididymis often show the presence of a cytoplasmic droplet attached to the annulus of the tail, indicative of impaired maturation. The flagella length is also significantly decreased in spermatozoa, especially in those cells with a cytoplasmic droplet. Spermatozoa display significantly lower motility than control sperm. However, sperm flagella display the characteristic 9 + 2 organization of axoneme microtubules (PubMed:23748901).|||Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly.|||Widely expressed in embryos during development with particularly high expression in the spinal cord at 13.5 dpc.|||Widely expressed with highest levels in neuronal tissues. In the brain, expressed in the cortex, cerebellum and hippocampus, including the pyramidal layers in CA1 and CA3, as well as the granular cell layers in the lateral blade (suprapyramidal portion) and the medial blade (infrapyramidal portion) of the dentate gyrus. In testis, mainly expressed in the internal cell layers of seminiferous tubules, where spermatocytes and spermatids are located.|||axon|||clathrin-coated pit|||cytoskeleton|||focal adhesion|||spindle http://togogenome.org/gene/10090:Ephb6 ^@ http://purl.uniprot.org/uniprot/O08644 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||High level in thymus, and brain. Very low levels of expression in kidney, lung, liver, bone marrow, skeletal muscle, spleen from 2 week old and adult mice, heart, testes and embryonic stem cells.|||Interacts with CBL and EPHB1. Interacts with FYN; this interaction takes place in a ligand-independent manner (By similarity).|||Kinase-defective receptor for members of the ephrin-B family. Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration by exerting both positive and negative effects upon stimulation with ephrin-B2. Inhibits JNK activation, T-cell receptor-induced IL-2 secretion and CD25 expression upon stimulation with ephrin-B2 (By similarity).|||Ligand-binding increases phosphorylation on tyrosine residues. Phosphorylation on tyrosine residues is mediated by transphosphorylation by the catalytically active EPHB1 in a ligand-independent manner. Tyrosine phosphorylation of the receptor may act as a switch on the functional transition from cell adhesion/attraction to de-adhesion/repulsion (By similarity).|||Secreted|||The protein kinase domain is predicted to be catalytically inactive. Its extracellular domain is capable of promoting cell adhesion and migration in response to low concentrations of ephrin-B2, but its cytoplasmic domain is essential for cell repulsion and inhibition of migration induced by high concentrations of ephrin-B2 (By similarity). http://togogenome.org/gene/10090:Plk2 ^@ http://purl.uniprot.org/uniprot/P53351|||http://purl.uniprot.org/uniprot/Q548A9 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation of Thr-236. Once activated, activity is stimulated by binding target proteins (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.|||Brain, lung and heart.|||Catalytic activity is enhanced by phosphorylation of Thr-236.|||Directly regulated by p53/TP53. Induced by serum and phorbol ester.|||Embryos display a delay in skeletal development and retarded growth. Embryonic fibroblasts proliferated slowly and displayed a delayed entry into S phase. Mice display loss of dendritic spines and impaired memory formation.|||Expressed in early G1, during G0-G1 transition as well as in cycling cells.|||Interacts with NSF; causing NSF dissociation from GRIA2 (By similarity). Interacts with CIB1.|||The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK2 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them (By similarity).|||Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.|||centriole|||dendrite http://togogenome.org/gene/10090:Or5w15 ^@ http://purl.uniprot.org/uniprot/Q8VFQ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Usp36 ^@ http://purl.uniprot.org/uniprot/B1AQJ2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Cytoplasm|||Deubiquitinase essential for the regulation of nucleolar structure and function. Required for cell and organism viability (PubMed:29273634). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:29273634). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (By similarity). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (By similarity). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (By similarity). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (By similarity). Deubiquitinates SOD2, regulates SOD2 protein stability (By similarity). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (By similarity). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (By similarity).|||Embryonic lethality (PubMed:29273634). Embryos show apoptosis at the morula stage, blocking the transition from morula to blastocysts during embryonic development (PubMed:29273634).|||Interacts with isoform 3 of FBXW7; the interaction inhibits MYC degradation induced by SCF(FBW7) complex. Interacts with NTRK1; USP36 does not deubiquitinate NTRK1. Interacts with NEDD4L (via domains WW1, 3 and 4); the interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and KCNQ3 by NEDD4L.|||Polyubiquitinated by NEDD4L, no effect on USP36 protein levels. Both proteins interact with and regulate each other's ubiquitination levels.|||nucleolus http://togogenome.org/gene/10090:Mmp13 ^@ http://purl.uniprot.org/uniprot/P33435|||http://purl.uniprot.org/uniprot/Q3U9V5 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||Detected in epidermal cells and stromal fibroblasts in wounded skin, but not in normal skin (at protein level). Detected in embryonic hypertrophic chondrocytes and newly recruited bone cells at primary ossification centers. After adult bone fracture, detected in periosteum and in chondrocytes in the cartilage. Detected in immature and mature osteoblasts in the fracture callus. Detected in calvaria from neonates. Detected in wounded skin, but not in normal skin.|||N-glycosylated.|||No visible phenotype. Mice are born at the expected Mendelian rate, are fertile and have a normal life span. Mutant embryos show a delay in the development of the primary ossification centers. Besides, they display an increased length of the growth plates of the long bones from the hind limbs (PubMed:15563592). Three week old mutant mice display an increased trabecular bone volume due to an increase in the length of the hypertrophic chondrocyte zone of the growth plate. This phenotype persists during several months (PubMed:15563592, PubMed:15539485), but one year old mutant mice display no longer any difference relative to wild-type (PubMed:15539485). After bone fractures, mutant mice show delays in carticage remodeling and resorption, as well as an increased volume of spongy bone mass. In addition, mutant mice show delayed healing of cutaneous wounds that is most evident three to seven days after wounding. The delay in wound healing and in re-epithelialization is exacerbated in mice lacking both Mmp13 and Mmp9.|||Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.|||Secreted|||The C-terminal region binds to collagen.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme (By similarity).|||The proenzyme is activated by removal of the propeptide; this cleavage can be effected by other matrix metalloproteinases, such as MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage can also be autocatalytic, after partial maturation by another protease or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro) (By similarity).|||Tyrosine phosphorylated by PKDCC/VLK.|||extracellular matrix http://togogenome.org/gene/10090:Pold3 ^@ http://purl.uniprot.org/uniprot/Q8BH76 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Krtap6-1 ^@ http://purl.uniprot.org/uniprot/O09048 ^@ Similarity|||Subunit ^@ Belongs to the KRTAP type 6 family.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Kcnb2 ^@ http://purl.uniprot.org/uniprot/A6H8H5 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.2/KCNB2 sub-subfamily.|||Cell membrane|||Homotetramer or heterotetramer with KCNB1. Heterotetramer with KCNS1 and KCNS2. Interacts (via phosphorylated FFAT motif) with VAPA and VAPB.|||Inhibited by quinine at micromolar levels. Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP).|||Perikaryon|||Phosphorylated (By similarity). Phosphorylation at Ser-608 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB (By similarity).|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells.|||dendrite http://togogenome.org/gene/10090:Lgals1 ^@ http://purl.uniprot.org/uniprot/P16045 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Binds LGALS3BP. Interacts with CD2, CD3, CD4, CD6, CD7, CD43, ALCAM and CD45. Interacts with laminin (via poly-N-acetyllactosamine). Interacts with SUSD2. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||Lectin that binds beta-galactoside and a wide array of complex carbohydrates. Plays a role in regulating apoptosis, cell proliferation and cell differentiation. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase. Strong inducer of T-cell apoptosis.|||Secreted|||Was originally thought to originate from human.|||extracellular matrix http://togogenome.org/gene/10090:Bin1 ^@ http://purl.uniprot.org/uniprot/O08539 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endosome|||Heterodimer with AMPH (By similarity). Binds SH3GLB1 (PubMed:12456676). Interacts (via SH3 domain) with DNM1. Interacts with SYNJ1 (By similarity). Interacts (via SH3 domain) with DNM2. Interacts with CLTC (By similarity). Interacts with AP2A2. Interacts with AP2B1 (By similarity). Interacts with MYC (via N-terminal transactivation domain); the interaction requires the integrity of the conserved MYC box regions 1 and 2 (PubMed:8782822). Interacts with BIN2 (By similarity). Interacts with SNX4 (PubMed:12668730). Interacts (via BAR domain) with BACE1 (By similarity). Binds (via BAR domain) F-actin (By similarity).|||Is a key player in the control of plasma membrane curvature, and membrane shaping and remodeling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling. Required in muscle cells for the formation of T-tubules, tubular invaginations of the plasma membrane that function in depolarization-contraction coupling (PubMed:12183633). Is a negative regulator of endocytosis (By similarity). Is also involved in the regulation of intracellular vesicles sorting, modulation of BACE1 trafficking and the control of amyloid-beta production (PubMed:12668730, PubMed:27179792). In neuronal circuits, endocytosis regulation may influence the internalization of PHF-tau aggregates (By similarity). May be involved in the regulation of MYC activity and the control cell proliferation (By similarity).|||Isoform 1 is expressed mainly in the brain. Isoform 2 is widely expressed.|||Nucleus|||Phosphorylated by protein kinase C.|||T-tubule http://togogenome.org/gene/10090:Adgrf5 ^@ http://purl.uniprot.org/uniprot/G5E8Q8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Deficient mice exhibit premature death, decreased body weight and respiratory distress associated with pulmonary alveolar proteinosis.|||Highly glycosylated.|||Homodimer; disulfide-linked. Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked. Fragment generates by the processing enzyme furin remains attached to the extracellular N-terminal fragment. Interacts (via N-terminal extracellular domain) with SFTPD (PubMed:23922714).|||Proteolytically cleaved at multiple sites: one in the GPS domain (S1 site) and the other in the SEA domain (S2 site). The proteolytic cleavage at S1 site generates an extracellular subunit and a seven-transmembrane subunit. The proteolytic cleavage at S2 site generates a fragment that undergoes proteolytic cleavage by the processing enzyme furin.|||Receptor that plays a critical role in lung surfactant homeostasis (PubMed:23590306, PubMed:23922714, PubMed:23684610). May play a role in controlling adipocyte function (PubMed:22971422).|||Widely expressed and highly expressed in the lung. In the lung predominantly expressed in the alveolar type II epithelial cells. http://togogenome.org/gene/10090:Trmt10c ^@ http://purl.uniprot.org/uniprot/Q3UFY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily. TRM10 family.|||Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3. Interacts with HSD17B10/MRPP2; forming the MRPP1-MRPP2 subcomplex of the mitochondrial ribonuclease P complex. Interacts with GRSF1.|||Mitochondrial tRNA N(1)-methyltransferase involved in mitochondrial tRNA maturation. Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3, which cleaves tRNA molecules in their 5'-ends. Together with HSD17B10/MRPP2, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity. The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; TRMT10C/MRPP1 acting as the catalytic N(1)-methyltransferase subunit. The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme. In addition to tRNA N(1)-methyltransferase activity, TRMT10C/MRPP1 also acts as a mRNA N(1)-methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA. Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Luc7l3 ^@ http://purl.uniprot.org/uniprot/Q5SUF2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Luc7 family.|||Binds cAMP regulatory element DNA sequence. May play a role in RNA splicing (By similarity).|||May interact with SFRS1 and form homodimers. Interacts with JMJD6. Interacts with RBM25. Interacts with RSRC1 (via Arg/Ser-rich domain). Interacts with RRP1B.|||Nucleus speckle http://togogenome.org/gene/10090:Gstk1 ^@ http://purl.uniprot.org/uniprot/Q9DCM2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-93 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the GST superfamily. Kappa family.|||Glutathione S-transferase that catalyzes the conjugation of glutathione to exogenous and endogenous compounds.|||Homodimer.|||Mitochondrion|||Predominantly expressed in heart, kidney, liver and skeletal muscle. http://togogenome.org/gene/10090:Map2k2 ^@ http://purl.uniprot.org/uniprot/Q63932|||http://purl.uniprot.org/uniprot/Q91YS7 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (PubMed:19219045). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (By similarity).|||Cytoplasm|||Expressed in adult intestine, kidney, liver, lung, pancreas, spleen, thymus, and at high levels in the neonatal brain. Lower expression is found in adult brain and heart.|||Inhibited by serine/threonine phosphatase 2A.|||Interacts with MORG1 (PubMed:15118098). Interacts with SGK1 (By similarity). Interacts with KSR1 (PubMed:10409742). Interacts with KSR1 and BRAF; the interaction with KSR1 mediates KSR1-BRAF dimerization (By similarity). Interacts with GLS (By similarity).|||Membrane|||Phosphorylation on Ser/Thr by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity. Phosphorylated by MAP2K1/MEK1. Low levels of autophosphorylation have been observed. http://togogenome.org/gene/10090:Gm14496 ^@ http://purl.uniprot.org/uniprot/K7N5U4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpr174 ^@ http://purl.uniprot.org/uniprot/Q3U507 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in spleen and, at low levels, in brain.|||Putative receptor for purines coupled to G-proteins. http://togogenome.org/gene/10090:Chil4 ^@ http://purl.uniprot.org/uniprot/Q91Z98 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.|||Cytoplasm|||Detected in stratified squamous epithelium in the junctional region between forestomach and glandular stomach (at protein level). Expression is mainly restricted to stomach.|||Has low chemotactic activity for eosinophils. May play a role in inflammation and allergy. Has no chitinase activity.|||Secreted|||Up-regulated in response to IL4 and IL13 and during the allergic response. http://togogenome.org/gene/10090:Comt ^@ http://purl.uniprot.org/uniprot/O88587 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.|||Cell membrane|||Cytoplasm http://togogenome.org/gene/10090:Blvrb ^@ http://purl.uniprot.org/uniprot/Q923D2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Broad specificity oxidoreductase that catalyzes the NADPH-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to heme catabolism and metabolizes linear tetrapyrroles. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. In the liver, converts biliverdin to bilirubin.|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Slc29a3 ^@ http://purl.uniprot.org/uniprot/Q99P65 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A truncated version of SLC29A3/mENT3 in which the N-terminal 36 amino acids are deleted, enables cell-surface localization of an otherwise intracellular transporter, and is utilized to investigate the transporter activity.|||Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.|||Cell membrane|||Contains a N-terminal dileucine motif (DE)XXXL(LI) important for endosomal/lysosomal and mitochondrial subcellular localization.|||Expressed in macrophages.|||In contrast with human ortholog, adenosine transport may be not pH-dependent.|||Knockout mice show lysosomal nucleoside buildup, elevated intralysosomal pH, altered macrophage function, and develop spontaneous and progressive macrophage-dominated histiocytosis.|||Late endosome membrane|||Lysosome membrane|||Mitochondrion membrane|||Uniporter that mediates the facilitative transport of nucleoside across lysosomal and mitochondrial membranes (PubMed:15701636, PubMed:22174130). Functions as a non-electrogenic Na(+)-independent transporter (PubMed:15701636). Substrate transport is pH-dependent and enhanced under acidic condition, probably reflecting the location of the transporter in acidic intracellular compartments (PubMed:15701636). Proton is not a cotransporting ion but most likely change the ionization state of the transporter which dictates transport-permissible/impermissible conformation for nucleoside translocation (By similarity). May direct the nucleoside transport from lysosomes to cytosol or cytosol to mitochondria to facilitate the fundamental function of salvage synthesis of nucleic acids (PubMed:22174130). Involved in the transport of nucleosides (adenosine, guanosine, uridine, thymidine, cytidine and inosine) and deoxynucleosides (deoxyadenosine, deoxycytidine) (PubMed:15701636, PubMed:22174130). Also mediates transport of purine nucleobases (adenine, guanine), and pyrimidine nucleobases (uracil) (PubMed:15701636). Also able to transport monoamine neurotransmitters dopamine, serotonin, noradrenaline and tyramine (By similarity). Capable of transporting ATP (By similarity). Mediates nucleoside export from lysosomes in macrophages, which regulates macrophage functions and numbers (PubMed:22174130). http://togogenome.org/gene/10090:Hdx ^@ http://purl.uniprot.org/uniprot/Q14B70 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Mcemp1 ^@ http://purl.uniprot.org/uniprot/Q9D8U6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cpa2 ^@ http://purl.uniprot.org/uniprot/Q504N0 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Secreted http://togogenome.org/gene/10090:Map4k2 ^@ http://purl.uniprot.org/uniprot/Q14B83|||http://purl.uniprot.org/uniprot/Q61161 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated in response to tumor necrosis factor (TNF), endotoxins or pro-inflammatory stimuli. Autophosphorylation leads to activation.|||Basolateral cell membrane|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Golgi apparatus membrane|||Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3 (By similarity). Interacts with RAB8A.|||May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.|||Polyubiquitinated through 'Lys-48'-polyubiquitin chains, allowing proteasomal turnover. Ubiquitination requires the kinase activity of MAP4K2/GCK.|||Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:8643544). Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway (By similarity). Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin (By similarity). To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation (By similarity). The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8 (By similarity). Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation (By similarity). Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3 (By similarity). May play a role in the regulation of vesicle targeting or fusion (By similarity).|||The PEST domains are Pro-, Glu-, Ser-, and Thr-rich domains. Proteins with PEST domains are frequently targets of degradation by the ubiquitin proteasome.|||The tumor necrosis factor (TNF), as well as endotoxins and pro-inflammatory stimuli such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation. http://togogenome.org/gene/10090:Or5al6 ^@ http://purl.uniprot.org/uniprot/A2ARY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lcn10 ^@ http://purl.uniprot.org/uniprot/Q0VBF7|||http://purl.uniprot.org/uniprot/Q810Z1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Expressed in epididymis.|||May play a role in male fertility. May act as a retinoid carrier protein within the epididymis.|||Secreted http://togogenome.org/gene/10090:Or3a10 ^@ http://purl.uniprot.org/uniprot/Q60891 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Mcrs1 ^@ http://purl.uniprot.org/uniprot/Q99L90 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts with NOP2. Interacts with PINX1. Interacts with TERT. Interacts with CCDC85B. Interacts with DAXX. Interacts (via N-terminus) with FMR1 (via phosphorylated form). Interacts with FXR1 and FXR2.|||Cytoplasm|||Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. May also be an inhibitor of TERT telomerase activity. Binds to G-quadruplex structures in mRNA. Binds to RNA homomer poly(G) and poly(U).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Six2 ^@ http://purl.uniprot.org/uniprot/Q62232 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SIX/Sine oculis homeobox family.|||Down-regulated by CTNNB1 upon differentiation. Activated by TLX1 in the kidney and repressed by HOXA2 in the branchial arch and facial mesenchyme.|||Expressed in phalangeal tendons, in smooth muscle and in head and body mesenchyme.|||First expressed at 8.5 dpc of embryo development in a restricted mesodermal subpopulation at the anterior hindbrain level. Expression of SIX2 in the developing limb begins at 11 dpc and is more pronounced ventrally. It progresses into the developing phalanges at 12.5 dpc. At 10.5 dpc expressed in the metanephric blastema, which signals the ureteric bud to evaginate from the Wolffian duct. At 11.5 dpc expressed at high levels in the dorsal anephric mesenchyme and is down-regulated where pretubular aggregates will form on the ventral side of the ureteric bud. At 14.5 dpc, expression persists in the peripheral mesenchyme of the renal cortex. At 9.5 dpc, expressed in the splanchnic mesoderm of the stomach anlage. By 10.5 dpc, expressed in the mesoderm of the posterior stomach. Expression is seen in the presumptive glandular stomach primordium at 11.5 dpc. At 12.5 dpc, becomes restricted to the mesenchyme of the antral region of the posterior stomach. At 14.5 dpc, expression remains in the antrum, just anterior to the pyloric sphincter.|||Interacts with TCF7L2; in a canonical Wnt signaling independent manner; prevents transcription of differentiation genes in cap mesenchyme. Interacts with OSR1; form a strong repressor complex with TCF7L2, TLE2 and TLE3 to prevent the activation of Wnt/beta-catenin target genes in the cap mesenchyme. Interacts with HOXA11, EYA1 and EYA3.|||Nucleus|||Six2 knockout heterozygous mice not exhibit any obvious abnormalities. However, Six2 knockout nullizygous mice die soon after birth.|||Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation (PubMed:20515681). During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1 (PubMed:19660448). During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway (PubMed:18321982). May also be involved in limb tendon and ligament development (PubMed:7720577). Plays a role in cell proliferation and migration (By similarity). http://togogenome.org/gene/10090:Morc1 ^@ http://purl.uniprot.org/uniprot/Q9WVL5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in embryonic testis at embryonic days 14.5 dpc and peaks at 16.5 dpc.|||Expressed at very low level in male germ cells.|||Mice show progressive loss of spermatogonia and male infertility (PubMed:10369865, PubMed:25503965). Spermatogenesis is blocked early in meiosis I (PubMed:10369865, PubMed:25503965). Male germ cells show derepression of transposable elements (TEs) and DNA hypomethylation of TEs (PubMed:25503965). Mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior are detectable and BDNF levels in the hippocampus are up-regulated (PubMed:26275923).|||Nucleus|||Required for spermatogenesis (PubMed:10369865, PubMed:25503965). Essential for de novo DNA methylation and silencing of transposable elements in the male embryonic germ cells (PubMed:25503965). Not required for piRNA biosynthesis (PubMed:25503965). http://togogenome.org/gene/10090:Abraxas1 ^@ http://purl.uniprot.org/uniprot/Q8BPZ8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM175 family. Abraxas subfamily.|||Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the complex, interacts directly with UIMC1/RAP80, BRCC3/BRCC36 and BABAM2. Homodimer. Interacts directly (when phosphorylated at Ser-404) with BRCA1. The phosphorylated homodimer can interact directly with two BRCA1 chains, giving rise to a heterotetramer. Binds polyubiquitin.|||Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX.|||Nucleus|||Phosphorylation of Ser-404 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1. http://togogenome.org/gene/10090:Tpp2 ^@ http://purl.uniprot.org/uniprot/Q64514 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S8 family.|||Cytoplasm|||Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway. It plays an important role in intracellular amino acid homeostasis (By similarity). Stimulates adipogenesis (PubMed:17932511).|||Expressed in the brain, skeletal muscle, gonadal and mesenteric white adipose tissue and brown adipose tissues.|||Homozygous mutant mice die in utero before embryonic day 9.0. Heterozygous mice display normal food intake but appear lean with a significant reduction in body fat, smaller adipocytes, decreased plasma insulin levels and less white adipose tissue in the gonad, groin and mesenteric regions.|||Nucleus|||The limitation of proteolytic products to tripeptides is achieved by tailoring the size of the substrate-binding cleft: the two negatively charged residues Glu-305 and Glu-331 that are blocking position P4 limit the number of residues that can be accommodated in the binding cleft and thus create a molecular ruler. At the same time, they orient substrates so that the tripeptides are removed exclusively from the N-terminus (By similarity). http://togogenome.org/gene/10090:Il13ra2 ^@ http://purl.uniprot.org/uniprot/O88786 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type I cytokine receptor family. Type 5 subfamily.|||Binds as a monomer with high affinity to interleukin-13 (IL13).|||Membrane|||Secreted|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. http://togogenome.org/gene/10090:Dcx ^@ http://purl.uniprot.org/uniprot/O88809 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Already expressed by 11 dpc, maximally around birth, expression decreasing gradually during the second postnatal week, with no expression in adult stages.|||Cytoplasm|||In neonatal tissues, highly expressed in brain, but not expressed in heart, liver, kidney and spleen. In adult tissues, faintly expressed in brain but not expressed in muscle, heart, lung, liver, spleen, intestine, kidney, testis and placenta.|||Interacts with tubulin. Interacts with USP9X.|||Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May participate along with PAFAH1B1/LIS-1 in a distinct overlapping signaling pathway that promotes neuronal migration.|||Phosphorylation by MARK1, MARK2 and PKA regulates its ability to bind microtubules (By similarity). Phosphorylation at Ser-265 and Ser-297 seems to occur only in neonatal brain, the levels falling precipitously by postnatal day 21 (PubMed:15099191, PubMed:22807455).|||Ubiquitinated by MDM2, leading to its degradation by the proteasome (PubMed:25088421). Ubiquitinated by MDM2 and subsequent degradation leads to reduce the dendritic spine density of olfactory bulb granule cells (PubMed:25088421).|||neuron projection http://togogenome.org/gene/10090:Tbc1d24 ^@ http://purl.uniprot.org/uniprot/Q3UUG6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Cytoplasmic vesicle membrane|||Expressed in brain, particularly at the level of the cortex and the hippocampus. Expressed in the inner ear in spiral ganglion cells, a collection of neurons critical for hearing and balance.|||Interacts with ARF6.|||May act as a GTPase-activating protein for Rab family protein(s) (PubMed:20727515). Involved in neuronal projections development, probably through a negative modulation of ARF6 function (PubMed:20727515). Involved in the regulation of synaptic vesicle trafficking (By similarity).|||Presynapse|||The Rab-GAP TBC domain is essential for phosphatidylinositol binding. http://togogenome.org/gene/10090:Cdk4 ^@ http://purl.uniprot.org/uniprot/P30285|||http://purl.uniprot.org/uniprot/Q545C3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequent activation.|||Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression (By similarity). Interacts with SEI1 and CCND1. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Interacts with FNIP1 and FNIP2 (By similarity).|||Cytoplasm|||Nucleus|||Nucleus membrane|||Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B (By similarity).|||Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (By similarity). http://togogenome.org/gene/10090:Cwc25 ^@ http://purl.uniprot.org/uniprot/Q9DBF7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC25 family.|||Identified in the spliceosome C complex.|||Involved in pre-mRNA splicing as component of the spliceosome.|||Nucleus http://togogenome.org/gene/10090:Rad21 ^@ http://purl.uniprot.org/uniprot/Q3TG35|||http://purl.uniprot.org/uniprot/Q61550 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a member of the cohesin complex, involved in sister chromatid cohesion from the time of DNA replication in S phase to their segregation in mitosis, a function that is essential for proper chromosome segregation, post-replicative DNA repair, and the prevention of inappropriate recombination between repetitive regions. The cohesin complex may also play a role in spindle pole assembly during mitosis (By similarity). In interphase, cohesins may function in the control of gene expression by binding to numerous sites within the genome (PubMed:18237772). May control RUNX1 gene expression. Binds to and represses APOB gene promoter (By similarity). May play a role in embryonic gut development, possibly through the regulation of enteric neuron development (By similarity).|||Belongs to the rad21 family.|||Chromosome|||Cleaved by separase/ESPL1 at the onset of anaphase; this cleavage is required for sister chromatid separation and cytokinesis. Cleaved by caspase-3/CASP3 or caspase-7/CASP7 at the beginning of apoptosis.|||Component of the cohesin complex, which consists of an SMC1A/B and SMC3 heterodimer core and 2 non-Smc subunits RAD21 and STAG1/SA1, STAG2/SA2 or STAG3/SA3 (PubMed:10375619, PubMed:18237772). Interacts (via C-terminus) with SMC1A and (via N-terminus) with SMC3; these interactions are direct (By similarity). The cohesin complex interacts with NUMA1. The cohesin complex also interacts with CDCA5, PDS5A and PDS5B; this interaction might regulate the ability of the cohesin complex to mediate sister chromatid cohesion. The interaction with PDS5B is direct and is stimulated by STAG1/SA1. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (By similarity). The cohesin complex interacts with DDX11/ChIR1. Directly interacts with WAPL; this interaction is stimulated by STAG1/SA1 (By similarity). Interacts with the ISWI chromatin remodeling complex component SMARCA5; the interaction is direct (By similarity). Interacts with the NuRD complex component CHD4; the interaction is direct (By similarity).|||May promote apoptosis.|||Not regulated during the cell cycle (at protein level).|||Nucleus|||Phosphorylated; becomes hyperphosphorylated in M phase of cell cycle. The large dissociation of cohesin from chromosome arms during prophase may be partly due to its phosphorylation by PLK1.|||Seems to bind calcium.|||The C-terminal part associates with the ATPase head of SMC1A, while the N-terminal part binds to the ATPase head of SMC3.|||Widely expressed with highest levels in testis, brain, kidney, heart and thymus. Lowest levels in skeletal muscle.|||centromere|||cytosol http://togogenome.org/gene/10090:Or8g21 ^@ http://purl.uniprot.org/uniprot/Q8VG16 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r111 ^@ http://purl.uniprot.org/uniprot/K7N674 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sox15 ^@ http://purl.uniprot.org/uniprot/P43267 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in myoblasts (at protein level) (PubMed:15367664). Expressed in embryonic stem cells (at protein level) (PubMed:15367664, PubMed:15863505). Expressed in myogenic progenitor cells (at protein level) (PubMed:17363903). Expressed in the ovary (PubMed:15367664). Expressed in kidney, liver, skeletal muscle, and testes (PubMed:10821863, PubMed:15367664). Expressed in lung and skin (PubMed:15863505). Expressed in the brain, heart, diaphragm, and intestines (PubMed:10821863). Expressed in the conceptus tissues of the placenta (PubMed:16759287).|||Highly expressed in the conceptus ectoplacental cone of the placenta at embryonic day 7.5 dpc (PubMed:16759287). Expressed in the conceptus trophoblast giant cell layer of the placenta (PubMed:16759287). Expressed in the trophoblast giant cells of the placenta from 10 dpc, expression peaks at 14 dpc, then reduces thereafter to 18 dpc (PubMed:16759287). Expression is increased during trophoblast differentiation (PubMed:16759287). Expressed at 8.5 dpc in developing embryos, with increased expression at 9.5 dpc (PubMed:10821863).|||Interacts with HAND1; the interaction enhances HAND1-induced differentiation of trophoblast giant cells (PubMed:16759287). Interacts with POU5F1 (OCT3/4); binds synergistically with POU5F1 to DNA (PubMed:15863505). Interacts with FHL3; the interaction recruits the transcriptional coactivator FHL3 to the FOXK1 promoter (PubMed:17363903).|||Knockout mice are viable, morphologically normal and fertile (PubMed:15367664, PubMed:15863505). Reduced regeneration of damaged skeletal muscle fibers following injury with increased numbers of mononuclear cells and a significant reduction in the number of myofibers (PubMed:15367664, PubMed:17363903). Impaired proliferation of myogenic progenitor cells, reduced number of satellite cells within the tibialis anterior muscles, and a decrease in FOXK1 expression (PubMed:17363903).|||Nucleus|||Transcription factor that binds to DNA at the 5'-AACAATG-3' consensus sequence (PubMed:10821863, PubMed:15863505, PubMed:16759287, PubMed:17363903). Acts as a transcriptional activator and repressor (PubMed:10821863, PubMed:15863505, PubMed:16759287). Binds synergistically with POU5F1 (OCT3/4) to gene promoters (PubMed:15863505). Binds to the FOXK1 promoter and recruits FHL3, resulting in transcriptional activation of FOXK1 which leads to myoblast proliferation (PubMed:17363903). Acts as an inhibitor of myoblast differentiation via transcriptional repression which leads to down-regulation of the muscle-specific genes MYOD and MYOG (PubMed:10821863). Involved in trophoblast giant cell differentiation via enhancement of HAND1 transcriptional activity (PubMed:16759287). Regulates transcription of HRC via binding to its proximal enhancer region (PubMed:15863505). Involved in skeletal muscle regeneration (PubMed:15367664, PubMed:17363903). Also plays a role in the development of myogenic precursor cells (PubMed:15367664). http://togogenome.org/gene/10090:Ppp6r2 ^@ http://purl.uniprot.org/uniprot/A0A5F8MQ25|||http://purl.uniprot.org/uniprot/G3X9K4|||http://purl.uniprot.org/uniprot/Q8C3X1 ^@ Similarity ^@ Belongs to the SAPS family. http://togogenome.org/gene/10090:Ddx20 ^@ http://purl.uniprot.org/uniprot/Q9JJY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX20 subfamily.|||Cytoplasm|||Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (By similarity). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (By similarity). Interacts with SMN1; the interaction is direct (PubMed:10767334). Interacts with GEMIN4; the interaction is direct (By similarity). Interacts with GEMIN5 (By similarity). Interacts with SNUPN; the interaction is direct (By similarity). Interacts with PPP4R2 (By similarity). Interacts with FOXL2 (PubMed:16153597). Interacts with NANOS1 and PUM2 (By similarity).|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs) (By similarity).|||gem http://togogenome.org/gene/10090:Bst2 ^@ http://purl.uniprot.org/uniprot/Q8R2Q8 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||By viral or other interferon-inducing stimulation in most cell types (at protein level). Down-regulated by ebola virus GP protein.|||Cell membrane|||Cytoplasm|||IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells. Acts as a direct physical tether, holding virions to the cell membrane and linking virions to each other. The tethered virions can be internalized by endocytosis and subsequently degraded or they can remain on the cell surface. In either case, their spread as cell-free virions is restricted. Its target viruses belong to diverse families, including retroviridae: human immunodeficiency virus type 1 (HIV-1), mouse mammary tumor virus (MMTV) and murine leukemia virus (MLV), filoviridae: ebola virus (EBOV), arenaviridae: lassa virus (LASV), and rhabdoviridae: vesicular stomatitis virus (VSV). Can inhibit cell surface proteolytic activity of MMP14 causing decreased activation of MMP15 which results in inhibition of cell growth and migration. Can stimulate signaling by LILRA4/ILT7 and consequently provide negative feedback to the production of IFN by plasmacytoid dendritic cells in response to viral infection. Plays a role in the organization of the subapical actin cytoskeleton in polarized epithelial cells.|||In naive mice, specifically expressed on type I interferon-producing cells (at protein level).|||Late endosome|||Membrane raft|||Parallel homodimer; disulfide-linked. May form homotetramers under reducing conditions. Dimerization is essential for its antiviral activity. Interacts (via cytoplasmic domain) with ARHGAP44 (By similarity). Interacts with MMP14 (via C-terminal cytoplasmic tail) (By similarity). Interacts with LILRA4/ILT7 (By similarity).|||The extracellular coiled coil domain forms an extended 170 A long semi-flexible rod-like structure important for virion retention at the cell surface and prevention of virus spreading.|||trans-Golgi network http://togogenome.org/gene/10090:Polr3b ^@ http://purl.uniprot.org/uniprot/P59470 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNA polymerase beta chain family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol III is composed of mobile elements and RPC2 is part of the core element with the central large cleft and probably a clamp element that moves to open and close the cleft. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fam120a ^@ http://purl.uniprot.org/uniprot/Q6A0A9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arg-980 is dimethylated, probably to asymmetric dimethylarginine.|||Belongs to the constitutive coactivator of PPAR-gamma family.|||Cell membrane|||Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases. May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase. Binds IGF2 RNA and promotes the production of IGF2 protein.|||Cytoplasm|||Expressed in the developing brain at 12 dpc. Expression increases postnatally and is maintained at an adult level beyond 4 weeks after birth (at protein level).|||In the brain, predominantly expressed in the hippocampus, caudate putamen, cerebral cortex and cerebellum. Expression is restricted to neurons (at protein level).|||Interacts with PURA (PubMed:18413649). Interacts with SRC family protein kinases YES1, SRC and FYN. Upon tyrosine phosphorylation, interacts with PIK3R1. Interacts with IGF2BP1/IMP-1 in an RNA-dependent manner (By similarity).|||Phosphorylated on tyrosine by src family kinases upon ultraviolet exposure. http://togogenome.org/gene/10090:Cfap119 ^@ http://purl.uniprot.org/uniprot/Q6NZQ0 ^@ Subcellular Location Annotation ^@ Cytoplasm|||acrosome|||flagellum http://togogenome.org/gene/10090:Pcdhb8 ^@ http://purl.uniprot.org/uniprot/Q91XZ2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane (PubMed:27161523). Each cadherin domain binds three calcium ions (PubMed:27161523).|||Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination (Probable). Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain (PubMed:27161523).|||Cell membrane|||Forms homodimers in trans (molecules expressed by two different cells) (PubMed:27161523). Forms promiscuous heterodimers in cis (at the plasma membrane of the same cell) with other protocadherins (PubMed:27161523). http://togogenome.org/gene/10090:Fam32a ^@ http://purl.uniprot.org/uniprot/Q9CR80 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAM32 family.|||May induce G2 arrest and apoptosis (By similarity). May also increase cell sensitivity to apoptotic stimuli (By similarity). In cell lines, may play a role in the inhibition of anchor-independent cell growth.|||Nucleus|||Widely expressed, with highest level in pancreas and lowest in muscle. http://togogenome.org/gene/10090:Csn1s1 ^@ http://purl.uniprot.org/uniprot/P19228|||http://purl.uniprot.org/uniprot/Q91VV1|||http://purl.uniprot.org/uniprot/Q99JM6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-casein family.|||Important role in the capacity of milk to transport calcium phosphate.|||Mammary gland specific. Secreted in milk.|||Secreted http://togogenome.org/gene/10090:Mcoln2 ^@ http://purl.uniprot.org/uniprot/Q8K595 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN2 sub-subfamily.|||Cell membrane|||Channel activity is reduced by low extracellular/lumenal pH level.|||Forms homooligomeric complexes; probably tetrameric. Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific. Interacts with TMEM176A.|||Isoform 1 is widely expressed at very low levels. Isoform 2 is expressed at high levels in lymphoid tissues (thymus and spleen) and kidney, and at moderate levels in heart, lung, liver and stomach. Expressed in activated macrophages and microglia (at protein level).|||Lysosome membrane|||No visible phenotype. The secretion of specific cytokines (CCL3, CCL5 and CXCL2) by macrophages exposed to bacterial lipopolysaccharide (LPS) is decreased. Mutant mice display decreased migration of macrophages into the intraperitoneal space after injection with LPS, or after infection with E.coli O78:H11 (strain H10407).|||Nonselective cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:19763610). May activate ARF6 and be involved in the trafficking of GPI-anchored cargo proteins to the cell surface via the ARF6-regulated recycling pathway (By similarity). May play a role in immune processes. In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (PubMed:17050035). In the innate immune response, may play a role in the regulation of chemokine secretion and macrophage migration (PubMed:26432893). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events.|||Recycling endosome membrane|||The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.|||Up-regulated in microglia cells and macrophages by bacterial lipopolysaccharide (LPS). Up-regulated by infection with M.smegmatis. http://togogenome.org/gene/10090:Hspa1l ^@ http://purl.uniprot.org/uniprot/A1L347|||http://purl.uniprot.org/uniprot/P16627 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||Expressed in spermatids.|||Interacts with PRKN.|||Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. Positive regulator of PRKN translocation to damaged mitochondria.|||Specifically expressed in postmeiotic phases of spermatogenesis.|||The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins. http://togogenome.org/gene/10090:Scart1 ^@ http://purl.uniprot.org/uniprot/Q8CGY7 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Kdm8 ^@ http://purl.uniprot.org/uniprot/Q9CXT6 ^@ Caution|||Cofactor|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bifunctional enzyme that acts both as an endopeptidase and 2-oxoglutarate-dependent monooxygenase. Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation. Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity. Upon DNA damage, cleaves the N-terminal tail of histone H3 at monomethylated lysine residues, preferably at monomethylated 'Lys-9' (H3K9me1). The histone variant H3F3A is the major target for cleavage. Additionnally, acts as Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (R)-stereospecific hydroxylation at C-3 of 'Arg-137' of RPS6 and 'Arg-141' of RCCD1, but the biological significance of this activity remains to be established. Regulates mitosis through different mechanisms: Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with RCCD1. Possibly together with RCCD1, is involved in proper mitotic spindle organization and chromosome segregation. Negatively regulates cell cycle repressor CDKN1A/p21, which controls G1/S phase transition. Required for G2/M phase cell cycle progression. Regulates expression of CCNA1/cyclin-A1, leading to cancer cell proliferation. Also, plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability involved in epithelial to mesenchymal transition (By similarity). Regulates the circadian gene expression in the liver (PubMed:30500822). Represses the transcriptional activator activity of the CLOCK-BMAL1 heterodimer in a catalytically-independent manner (By similarity). Negatively regulates the protein stability and function of CRY1; required for AMPK-FBXL3-induced CRY1 degradation (PubMed:30500822).|||Binds 1 Fe(2+) ion per subunit.|||Can form homodimers (via JmjC domain). Found in a complex with RCCD1. Interacts (via N-terminus) with RCCD1 (via N-terminus); this interaction stimulates H3K36me3 and H3K36me2 demethylation. Interacts (via JmjC domain) with H3C1 (By similarity). Interacts with FBXL3 and PSMD2 (PubMed:30500822). Interacts with CRY1 in a FBXL3-dependent manner (PubMed:30500822).|||Chromosome|||Conditional knockout in liver leads to disruption of circadian gene expression in the liver.|||Expressed in a circadian manner in the liver.|||Nucleus|||The demethylase activity of JMJD5 is controversial. Demethylase activity towards H3K36me2 was observed in vivo and in vitro. In addition, demethylase activity towards H3K36me3 when in a complex with RCCD1 has been observed. In contrast, in other studies, JMJD5 was shown not to display any demethylase activity toward methylated H3K36 nor toward other methyllysines in the N-terminal tails of H3 and H4 in vitro. http://togogenome.org/gene/10090:Ceacam10 ^@ http://purl.uniprot.org/uniprot/Q61400 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in seminal vesicle and traces in epididymis and prostate (at protein level). Highly expressed in seminal vesicle, minor in colon and placenta and, to a lesser extent, in small intestine, caecum, stomach, salivary gland and bone marrow.|||Belongs to the immunoglobulin superfamily. CEA family.|||May interact with other CEACAM proteins on the sperm surface.|||Present in trace amounts on 5.5 dpc, increased remarkably from 6.5 dpc to a maximum on 9.5 dpc and rapidly declined thereafter to an almost undetectable level until delivery. First appeared at a considerable level in 3-week-old mice. Thereafter, the amount of transcript began increasing rapidly at 4-week-old mice and reached a maximum in 7-week-old mice.|||extracellular space http://togogenome.org/gene/10090:Snf8 ^@ http://purl.uniprot.org/uniprot/Q9CZ28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF8 family.|||Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS25 and VPS36. SNF8 is essential for the stability of the ESCRT-II complex. ESCRT-II interacts with ELL. Interacts with TSG101 (via the C-terminal domain). Interacts with RILPL1 (via the N-terminal domain); which recruits ESCRT-II to the endosome membranes. Interacts with 14-3-3 proteins (By similarity).|||Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).|||Cytoplasm|||Endosome membrane|||Late endosome membrane|||Nucleus http://togogenome.org/gene/10090:Ndufb6 ^@ http://purl.uniprot.org/uniprot/A2AP31|||http://purl.uniprot.org/uniprot/Q3UIU2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB6 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Zfp385c ^@ http://purl.uniprot.org/uniprot/A2A5E6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Agfg2 ^@ http://purl.uniprot.org/uniprot/Q80WC7 ^@ Domain|||Subunit ^@ Contains FG repeats and 4 N-P-F repeats.|||Interacts with EPS15R. http://togogenome.org/gene/10090:Mrto4 ^@ http://purl.uniprot.org/uniprot/A2AMU9|||http://purl.uniprot.org/uniprot/A2AMV1|||http://purl.uniprot.org/uniprot/Q9D0I8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the pre-60S ribosomal particle.|||Associates with the pre-60S ribosomal particle. Interacts with MINAS-60 (product of an alternative open reading frame of RBM10).|||Belongs to the universal ribosomal protein uL10 family.|||Component of the ribosome assembly machinery. Nuclear paralog of the ribosomal protein P0, it binds pre-60S subunits at an early stage of assembly in the nucleolus, and is replaced by P0 in cytoplasmic pre-60S subunits and mature 80S ribosomes.|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Oscp1 ^@ http://purl.uniprot.org/uniprot/Q8BHW2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Basal cell membrane|||May be involved in drug clearance in the placenta.|||Predominantly expressed in testis. http://togogenome.org/gene/10090:Cdkn2b ^@ http://purl.uniprot.org/uniprot/P55271 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.|||By TGF-beta.|||Expressed ubiquitously.|||Heterodimer of CDKN2B with CDK4 or CDK6.|||Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest (By similarity). http://togogenome.org/gene/10090:Mael ^@ http://purl.uniprot.org/uniprot/Q8BVN9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the maelstrom family.|||Cytoplasm|||Interacts with SMARCB1, SIN3B and DDX4. Interacts with piRNA-associated proteins TDRD1, PIWIL1 and PIWIL2. Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886).|||Mice are viable but show profound defect in synapsis of homologous chromosomes in male meiosis, piRNA production defects, DNA demethylation of LINE-1 (L1) transposable elements and a 100-fold increase in L1 expression in the adult testis. In the adult testes, L1 transposon derepression occurs at the onset of meiosis. As a result, spermatocytes are flooded with L1 ribonucleoproteins (RNPs) that accumulates in large cytoplasmic enclaves and nuclei. Spermatocytes with nuclear L1 RNPs exhibit massive DNA damage and severe chromosome asynapsis. In gonocytes, PIWIL4, TDRD9, and DDX4 are lost from piP-bodies, whereas no effects on pi-body composition are observed.|||Nucleus|||Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage.|||Present from 12.5 dpc, although at this stage, protein levels are low. In the male, from 12.5 until 14.5 cpc, it localizes to the cytoplasm of germ cells, but from 15.5-16.5 dpc, it localizes to the nucleus as well. In the female, it is cytoplasmic in germ cells throughout embryonic gonad development (at protein level). In testis, low levels are observed in the early stages of meiotic prophase I (leptonema to midpachynema). Starts to accumulate throughout the cytoplasm and in prominent perinuclear nuage in late pachytene and diplotene spermatocytes. Meiotic metaphases and secondary spermatocytes show a high level in the cytoplasm as well as in nuage. Present in the chromatoid body and in a second smaller nuage in round spermatids (at protein level).|||Testis-specific. Present in spermatocytes and round and early elongating spermatids. http://togogenome.org/gene/10090:Trip4 ^@ http://purl.uniprot.org/uniprot/Q9QXN3 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in 17.5-day-old embryos.|||Interacts with the thyroid hormone receptor/TR (via the ligand-binding domain); this interaction requires the presence of thyroid hormone (By similarity). Interacts with the androgen receptor/AR; in an androgen, testosterone and dihydrotestosterone-dependent manner (By similarity). Interacts with ESR1 (estrogen ligand-bound); competes with UFSP2 (By similarity). Interacts with UFSP2; competes with ligand-bound ESR1 (By similarity). Interacts with DDRGK1 and UFL1; the interaction with DDRGK1 is direct (By similarity). Interacts with NCOA1 (By similarity). Interacts with EP300 (By similarity). Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3 (PubMed:12077347). Identified in the RQT (ribosome quality control trigger) complex, that contains ASCC2, ASCC3 and TRIP4 (By similarity). Interacts with NEK6 (By similarity). Interacts with CSRP1 (By similarity). Interacts with ZCCHC4 (By similarity).|||Nucleus|||Phosphorylated by NEK6.|||Polyufmylated by the UFM1-conjugating system composed of the enzymes UBA5, UFC1 and UFL1. Deufmylated by the protease UFSP2. Ufmylation of TRIP4 is promoted by ligand-bound nuclear receptors that compete with UFSP2 for interaction with TRIP4. Nuclear receptors-induced ufmylation promotes the recruitment of additional transcriptional coactivators like EP300 and NCOA1 and therefore the assembly of a coactivator complex facilitating nuclear receptor-mediated transcription.|||The C4-type zinc finger mediates a competitive interaction with UFSP2 and ligand-bound nuclear receptors. It also mediates interaction with the transcriptional coactivators and the basal transcription machinery.|||Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription. May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions. Plays a role in thyroid hormone receptor and estrogen receptor transactivation (By similarity). Also involved in androgen receptor transactivation (PubMed:12077347). Plays a pivotal role in the transactivation of NF-kappa-B, SRF and AP1. Acts as a mediator of transrepression between nuclear receptor and either AP1 or NF-kappa-B. May play a role in the development of neuromuscular junction (By similarity). May play a role in late myogenic differentiation (PubMed:27008887). Also functions as part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (By similarity).|||Ubiquitously expressed (PubMed:12390891). Expressed in the spinal cord, brain, paraspinal ganglia, thyroid, and submandibular glands (PubMed:26924529). Expressed at low level in all the muscles (at protein level) but with higher expression in axial than in limb muscles (PubMed:27008887).|||centrosome|||cytosol http://togogenome.org/gene/10090:Vpreb1a ^@ http://purl.uniprot.org/uniprot/P13372 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the Ig-mu chain to form a molecular complex that is expressed on the surface of pre-B-cells. This complex presumably regulates Ig gene rearrangements in the early steps of B-cell differentiation.|||Belongs to the immunoglobulin superfamily.|||Endoplasmic reticulum|||Interacts with IGLL1 (By similarity). Interacts with SYNV1/HRD1 (via N-terminus); this interaction leads to increased VPREB1 ubiquitination and degradation in pre-B cells, possibly through a lysosomal, not proteasomal, pathway (PubMed:29907570).|||Only expressed by pre-B-cells. http://togogenome.org/gene/10090:Cstf2t ^@ http://purl.uniprot.org/uniprot/Q8C7E9 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in testes, where it is restricted to pachytene spermatocytes and spermatids, and in the brain (at protein level).|||May play a significant role in AAUAAA-independent mRNA polyadenylation in germ cells. Directly involved in the binding to pre-mRNAs.|||Nucleus http://togogenome.org/gene/10090:Larp1 ^@ http://purl.uniprot.org/uniprot/Q6ZQ58 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 10.5 dpc, expressed in dorsal root ganglia, spinal cord, and branchial arches. At 14.5 dpc, expressed in olfactory epithelium and cranial sensory ganglia. Also expressed in salivary glands, lungs, gut, kidney, teeth and vibrissae.|||Belongs to the LARP family.|||Conflicting results are reported regarding the interaction with PABPC1. Some studies found that the interaction depends on the presence of mRNA; others found that the interaction is direct and does not depend on the presence of mRNA.|||Cytoplasm|||Cytoplasmic granule|||Interacts with PABPC1/PABP. Interacts with EIF4A1. Interacts with RPTOR. Recruited to the active mTORC1 complex via interaction with RPTOR. Inhibition of mTORC1 activity strongly reduces interaction with RPTOR and the mTORC1 complex. Identified in a complex with mRNA, PABPC1, EIF4E and EIF4G1. Found in a complex with PABPC1 and SHFL.|||Phosphorylated on multiple Ser and Thr residues in response to active mTORC1. Phosphorylation is important for interaction with RPTOR and the mTORC1 complex. Phosphorylation promotes dissociation from the 5'UTR of mRNA molecules with a 5'TOP motif.|||RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability. Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery. The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1. When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA. Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif. Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes. Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis. Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation. Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis.|||The C-terminal region mediates interaction with the mRNA and polysomes. It is required for translational repression of mRNAs with a 5'TOP motif.|||The N-terminal region mediates interaction with PABPC1. http://togogenome.org/gene/10090:Or8b12b ^@ http://purl.uniprot.org/uniprot/Q7TRE5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fa2h ^@ http://purl.uniprot.org/uniprot/Q5MPP0 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sterol desaturase family. SCS7 subfamily.|||Binds 2 Zn(2+) ions per subunit that likely form a catalytic dimetal center.|||Catalyzes the hydroxylation of free fatty acids at the C-2 position to produce 2-hydroxy fatty acids, which are building blocks of sphingolipids and glycosphingolipids common in neural tissue and epidermis (PubMed:15658937, PubMed:16998236, PubMed:22517924). FA2H is stereospecific for the production of (R)-2-hydroxy fatty acids (PubMed:22517924). Plays an essential role in the synthesis of galactosphingolipids of the myelin sheath (PubMed:15658937, PubMed:18815260). Responsible for the synthesis of sphingolipids and glycosphingolipids involved in the formation of epidermal lamellar bodies critical for skin permeability barrier (By similarity). Participates in the synthesis of glycosphingolipids and a fraction of type II wax diesters in sebaceous gland, specifically regulating hair follicle homeostasis (PubMed:21628453). Involved in the synthesis of sphingolipids of plasma membrane rafts, controlling lipid raft mobility and trafficking of raft-associated proteins (PubMed:22517924).|||Endoplasmic reticulum membrane|||Expressed in brain (at protein level) (PubMed:16998236). Detected in cerebellum and forebrain (PubMed:18815260, PubMed:15658937). Expression in the white matter is mainly restricted in oligodendrocytes (PubMed:15658937). Expressed in stomach, kidney, skin and testis (PubMed:15658937). Expressed in sebaceous gland (PubMed:21628453).|||Knockout mice have normal oligodentrocyte differentiation and develope structural and functional normal myelin up to early adulthood. However, aged knockout mice show a massive axon and myelin sheath degeneration in the spinal cord (PubMed:18815260). Knockout mice show delayed fur development and a cyclic alopecia (PubMed:21628453).|||Levels increase rapidly in brains from newborns, in parallel with myelination in the central nervous system. Present at very low levels in newborns. Levels are highest at 2 to 3 weeks, and then decrease slightly to reach an constant, intermediate level after 4 months. Constitutively expressed at an intermediate level throughout adult life.|||Microsome membrane|||The N-terminal cytochrome b5 heme-binding domain is essential for catalytic activity.|||The histidine box domains may contain the active site and/or be involved in metal ion binding. http://togogenome.org/gene/10090:Apbb3 ^@ http://purl.uniprot.org/uniprot/Q8R1C9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with APP (via intracellular domain) (By similarity). Interacts with APLP1 and APLP2 (via intracellular domain) (By similarity).|||May modulate the internalization of amyloid-beta precursor protein.|||Nucleus http://togogenome.org/gene/10090:Kras ^@ http://purl.uniprot.org/uniprot/P32883 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).|||Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP). Interaction with SOS1 promotes exchange of bound GDP by GTP.|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Cytoplasm|||Endomembrane system|||Interacts (when farnesylated) with GPR31.|||Interacts with PHLPP. Interacts (active GTP-bound form preferentially) with RGS14 (By similarity). Interacts (when farnesylated) with PDE6D; this promotes dissociation from the cell membrane. Interacts with SOS1 (By similarity). Interacts (when farnesylated) with GPR31 (By similarity). Interacts with RAP1GDS1 (By similarity).|||Palmitoylated at Lys-182, Lys-184 and Lys-185. Lysine-depalmitoylation by SIRT2 promotes its localization to endomembranes in endocytic pathways.|||Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (By similarity). Plays an important role in the regulation of cell proliferation (PubMed:6474169, PubMed:1352876). Plays a role in promoting oncogenic events by inducing transcriptional silencing of tumor suppressor genes (TSGs) in colorectal cancer (CRC) cells in a ZNF304-dependent manner (By similarity).|||This gene is amplified in the mouse adrenal tumor Y1 cells, and is also directly linked to lung tumor susceptibility.|||Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes. http://togogenome.org/gene/10090:Gm20863 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Yipf7 ^@ http://purl.uniprot.org/uniprot/Q9JIM5 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the YIP1 family.|||Endoplasmic reticulum membrane|||Specifically expressed in the heart.|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Trim42 ^@ http://purl.uniprot.org/uniprot/Q9D2H5 ^@ Similarity ^@ Belongs to the TRIM/RBCC family. http://togogenome.org/gene/10090:Or5an9 ^@ http://purl.uniprot.org/uniprot/Q8VF59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnpo2 ^@ http://purl.uniprot.org/uniprot/E9PV58|||http://purl.uniprot.org/uniprot/Q3U1S0|||http://purl.uniprot.org/uniprot/Q99LG2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the importin beta family. Importin beta-2 subfamily.|||Cytoplasm|||Nucleus|||Probably functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). http://togogenome.org/gene/10090:Nfrkb ^@ http://purl.uniprot.org/uniprot/Q6PIJ4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NFRKB family.|||Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'.|||Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80. Interacts with UCHL5 (By similarity).|||NFRKB seems to be mostly disordered. The wing-helix like domain doesn't bind DNA (By similarity).|||Nucleus|||Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex (By similarity). http://togogenome.org/gene/10090:Mis18a ^@ http://purl.uniprot.org/uniprot/Q9CZJ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mis18 family.|||Chromosome|||Homodimer, and heterodimer with OIP5/MIS18B. Identified in a complex containing MIS18A, OIP5/MIS18B, MIS18BP1, RBBP7 and RBBP4.|||Nucleus|||Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.|||centromere http://togogenome.org/gene/10090:S100z ^@ http://purl.uniprot.org/uniprot/B9EJL3 ^@ Similarity ^@ Belongs to the S-100 family. http://togogenome.org/gene/10090:Rnaseh1 ^@ http://purl.uniprot.org/uniprot/E9QLN8 ^@ Function|||Similarity ^@ Belongs to the RNase H family.|||Endonuclease that specifically degrades the RNA of RNA-DNA hybrids. http://togogenome.org/gene/10090:Dhrs11 ^@ http://purl.uniprot.org/uniprot/Q3U0B3 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5-alpha-androstanes into their 17-beta-hydroxyl metabolites and the conversion of the 3-keto group of 3-, 3,17- and 3,20- diketosteroids into their 3-hydroxyl metabolites. Exhibits reductive 3-beta-hydroxysteroid dehydrogenase activity toward 5-beta-androstanes, 5-beta-pregnanes, 4-pregnenes and bile acids. May also reduce endogenous and exogenous alpha-dicarbonyl compounds and xenobiotic alicyclic ketones.|||Homotetramer.|||Inhibited by flavonoids including apigenin, luteolin, genistein, kaempferol and quercetin and also by carbenoxolone, zearalenone, glycyrrhetinic, curcumin and flufenamic acid.|||It is uncertain whether Met-1 or Met-6 is the initiator.|||Secreted http://togogenome.org/gene/10090:Cdk5rap2 ^@ http://purl.uniprot.org/uniprot/Q0VGR5|||http://purl.uniprot.org/uniprot/Q8K389 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in the developing cortex at 9.5 dpc. Expression peaks between 10.5 and 13.5 dpc, remains robust at 15.5 dpc and declines thereafter. This peak corresponds to periods of active neurogenesis.|||Expressed in testis, thymus, heart and brain.|||Golgi apparatus|||Interacts with CDK5R1 (p35 form) (By similarity). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. May form a complex with CDK5R1 and CDK5 (By similarity). Interacts (via C-terminus) with PCNT; the interaction is leading to centrosomal localization of CDK5RAP2 and PCNT. Interacts with AKAP9; the interaction is leading to Golgi localization of CDK5RAP2 and AKAP9 (By similarity). Interacts with TUBG1; the interaction is leading to the centrosomal localization of CDK5RAP2 and TUBG1 (By similarity). Interacts with TUBGCP3 (By similarity). Interacts with CALM1 (By similarity). Interacts with CDC20 (By similarity). Interacts with CEP68; degradation of CEP68 in early mitosis leads to removal of CDK5RAP2 from the centrosome which promotes centriole disengagement and subsequent centriole separation (By similarity). Interacts with NCKAP5L (By similarity). Interacts with LGALS3BP; this interaction may connect the pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) to promote microtubule assembly and acetylation (By similarity). Contrary to human, chimpanzee, bovine and dog orthologous proteins, does not interact with EB1/MAPRE1, possibly due to a divergence at the level of the critical residue 940, which is a proline in MAPRE1-binding orthologs and a leucine in mouse and rat (PubMed:19553473).|||Phosphorylated in vitro by CDK5.|||Potential regulator of CDK5 activity via its interaction with CDK5R1. Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion (PubMed:20627074). Involved in regulation of mitotic spindle orientation (PubMed:20460369). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter. Required for the recruitment of AKAP9 to centrosomes (By similarity). Plays a role in neurogenesis (PubMed:20471352). Contrary to higher mammalian orthologs, including human, chimpanzee, bovine and dog, does not interact with EB1/MAPRE1, therefore its function in the regulation of microtubule dynamics is unclear (PubMed:19553473).|||centrosome http://togogenome.org/gene/10090:Ppp1ca ^@ http://purl.uniprot.org/uniprot/P62137 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP phosphatase family. PP-1 subfamily.|||Binds 1 Fe cation per subunit.|||Binds 2 manganese ions per subunit.|||Cytoplasm|||Nucleus|||PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R9A, PPP1R9B and PPP1R7. Interacts with PPP1R15A; the interaction mediates binding to EIF2S1. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B. Interacts. with RPSA only in the presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with PPP1R39. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site (By similarity). Interacts with PPP1R15B; the interaction mediates binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with NEK2. Interacts with FER; this promotes phosphorylation at Thr-320 (By similarity). Interacts with PHACTR4; which acts as an activator of PP1 activity. Interacts with BTBD10 (PubMed:18160256). Interacts with KCTD20 (PubMed:24156551). Interacts with FOXP3 (By similarity). Interacts with CENPA (By similarity). Interacts with ATG16L1 (By similarity). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity). Interacts with tensin TNS1 (By similarity). Interacts with SAXO4, PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and ELFN2 (By similarity).|||Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation (By similarity).|||Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates CENPA (By similarity). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Caprin2 ^@ http://purl.uniprot.org/uniprot/E4NKG5|||http://purl.uniprot.org/uniprot/Q05A80 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the caprin family.|||Cell membrane|||Cytoplasm|||Detected at 17.5 dpc in brain (at protein level).|||Homotrimer; via C1q domain. Found in a complex with LRP6, CCNY and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus. Interacts with LRP5. Interacts with LRP6.|||Promotes phosphorylation of the Wnt coreceptor LRP6, leading to increased activity of the canonical Wnt signaling pathway (By similarity). Facilitates constitutive LRP6 phosphorylation by CDK14/CCNY during G2/M stage of the cell cycle, which may potentiate cells for Wnt signaling (By similarity). May regulate the transport and translation of mRNAs, modulating for instance the expression of proteins involved in synaptic plasticity in neurons (PubMed:20516077). Involved in regulation of growth as erythroblasts shift from a highly proliferative state towards their terminal phase of differentiation (By similarity). May be involved in apoptosis (By similarity).|||Specifically expressed in brain (at protein level).|||The C1q domain is essential for the function in Wnt signaling.|||The sequence shown here is derived from an EMBL/GenBank/DDBJ third party annotation (TPA) entry. http://togogenome.org/gene/10090:Erp29 ^@ http://purl.uniprot.org/uniprot/P57759 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Does not seem to be a disulfide isomerase. Plays an important role in the processing of secretory proteins within the endoplasmic reticulum (ER), possibly by participating in the folding of proteins in the ER.|||Endoplasmic reticulum lumen|||Homodimer. Part of a large chaperone multiprotein complex comprising CABP1, DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX (By similarity).|||Melanosome http://togogenome.org/gene/10090:Diablo ^@ http://purl.uniprot.org/uniprot/Q9JIQ3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highest expression found in heart, liver, kidney and testis.|||Homodimer (By similarity). Interacts with BIRC2/c-IAP1 (By similarity). Interacts with BIRC6/bruce (By similarity). Interacts with BIRC7/livin (By similarity). Interacts with the monomeric and dimeric form of BIRC5/survivin (By similarity). Interacts with XIAP/BIRC4 (via BIR3 domain) (By similarity). Interacts with BEX3 (PubMed:15178455). Interacts with AREL1 (via HECT domain); in the cytoplasm following induction of apoptosis (PubMed:23479728).|||Mitochondrion|||Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases (By similarity).|||The mature N-terminus mediates interaction with XIAP/BIRC4.|||The precursor form is proteolytically cleaved by mitochondrial processing peptidase MPP to remove the transit peptide and produce an intermediate form. This is then processed by PARL to produce the mature cleaved form which is released from mitochondria into the cytosol in apoptotic cells.|||Ubiquitinated by BIRC7/livin.|||cytosol http://togogenome.org/gene/10090:Cyp2t4 ^@ http://purl.uniprot.org/uniprot/E9PWV0 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:H2-M10.3 ^@ http://purl.uniprot.org/uniprot/Q85ZW6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Sox12 ^@ http://purl.uniprot.org/uniprot/Q04890 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in splenic and thymic regulatory T-cells (at protein level) (PubMed:30190287). Expressed in embryonic molar and incisor teeth (PubMed:8921394).|||Induced by T-cell receptor signaling in naive CD4-positive T-cells and in splenic and thymic regulatory T-cells (PubMed:30190287). Up-regulated in splenic T reg cells by dextran sulfate sodium (DSS)-induced colitis (PubMed:30190287).|||Knockout mice are viable, fertile and morphologically normal (PubMed:18505825, PubMed:20596238). Increased expression of Sox11 in brain and cartilage at 14.5 dpc, with increased expression in liver and kidney at 16.5 dpc (PubMed:18505825). Increased expression of Sox4 in spinal cord and cartilage at 14.5 dpc, with increased expression in liver at 16.5 dpc (PubMed:18505825). Sox12 knockout naive CD4-positive T cells fail to differentiate into pT reg cells in mice with dextran sulfate sodium (DSS)-induced colitis (PubMed:30190287). Sox4, Sox11, and Sox12 triple knockout mice are embryonically lethal and show severe thinning and undulation of the neural tube (PubMed:20596238).|||Nucleus|||Transcription factor that binds to DNA at the consensus sequence 5'-ACCAAAG-3' (PubMed:18505825, PubMed:18403418, PubMed:30190287). Acts as a transcriptional activator (PubMed:18505825, PubMed:18403418, PubMed:30190287). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation (PubMed:18505825, PubMed:18403418). Involved in the differentiation of naive CD4-positive T-cells into peripherally induced regulatory T (pT reg) cells under inflammatory conditions (PubMed:30190287). Binds to the promoter region of the FOXP3 gene and promotes its transcription, and might thereby contribute to pT reg cell differentiation in the spleen and lymph nodes during inflammation (PubMed:30190287). Plays a redundant role with SOX4 and SOX11 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis (PubMed:20596238).|||Widely expressed in the developing embryo from 9.5 dpc to 12.5 dpc (PubMed:8441686, PubMed:18505825, PubMed:18403418, PubMed:20596238). Expressed throughout the central and peripheral nervous system, as well as the mesenchyme of many developing organs between 12.5 dpc and 14.5 dpc (PubMed:18403418). Strongly expressed in the lens of the eye, developing cerebral cortex, the dorsal cortical plate, thalamus, hippocampus and cerebellar cortex in the brain at 14.5 dpc (PubMed:18505825). Expressed in skin, spinal cord, lung, liver, intestine, kidney, heart, muscle, cartilage from 14.5 dpc to 18.5 dpc (PubMed:18505825). Abundantly expressed in the brain, heart and lung, with low expression in the liver, pancreas, and small intestine at postnatal day 2 (PubMed:18403418). http://togogenome.org/gene/10090:Alas2 ^@ http://purl.uniprot.org/uniprot/A2AFM0|||http://purl.uniprot.org/uniprot/A2AFM1|||http://purl.uniprot.org/uniprot/P08680 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.|||C-terminus is a mobile self-inhibitory loop which interferes directly with active site.|||Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products (PubMed:3557128, PubMed:8268805). Contributes significantly to heme formation during erythropoiesis (By similarity).|||Homodimer. Interacts with SUCLA2.|||Mitochondrion|||Mitochondrion inner membrane|||Predomnantly expressed in erythroid cells. http://togogenome.org/gene/10090:Slco2a1 ^@ http://purl.uniprot.org/uniprot/Q3TED0|||http://purl.uniprot.org/uniprot/Q9EPT5 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basal cell membrane|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Cytoplasm|||Higher dietary salt intake stimulates transcription (PubMed:18579702). Chorionic gonadotropin stimulates expression in the ovaries (PubMed:27169804).|||Highly expressed in lung and liver (PubMed:10484490). Expressed at lower levels in kidney and skeletal muscle (PubMed:10484490, PubMed:18579702). Expressed in the ovaries (at mRNA and protein levels) (PubMed:27169804). Expressed in peritoneal macrophages (at mRNA and protein levels) (PubMed:26474801).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lysosome|||Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane (PubMed:10484490) (Probable). PGs and thromboxanes play fundamental roles in diverse functions such as intraocular pressure, gastric acid secretion, renal salt and water transport, vascular tone, and fever (By similarity). Plays a role in the clearance of PGs from the circulation through cellular uptake, which allows cytoplasmic oxidation and PG signal termination (PubMed:10484490) (Probable). PG uptake is dependent upon membrane potential and involves exchange of a monovalent anionic substrate (PGs exist physiologically as an anionic monovalent form) with a stoichiometry of 1:1 for divalent anions or of 1:2 for monovalent anions (By similarity). Uses lactate, generated by glycolysis, as a counter-substrate to mediate PG influx and efflux. Under nonglycolytic conditions, metabolites other than lactate might serve as counter-substrates. Although the mechanism is not clear, this transporter can function in bidirectional mode (By similarity). When apically expressed in epithelial cells, it facilitates transcellular transport (also called vectorial release), extracting PG from the apical medium and facilitating transport across the cell toward the basolateral side, whereupon the PG exits the cell by simple diffusion (PubMed:18579702). In the renal collecting duct, regulates renal Na+ balance by removing PGE2 from apical medium (PGE2 EP4 receptor is likely localized to the luminal/apical membrane and stimulates Na+ resorption) and transporting it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors inhibit Na+ resorption) (PubMed:18579702). Plays a role in endometrium during decidualization, increasing uptake of PGs by decidual cells (By similarity). Involved in critical events for ovulation (PubMed:27169804). Regulates extracellular PGE2 concentration for follicular development in the ovaries (PubMed:27169804). When expressed intracellularly, such as in macrophages, contributes to vesicular uptake of newly synthesized intracellular PGs, thereby facilitating exocytotic secretion of PGs without being metabolized (PubMed:26474801). Essential core component of the major type of large-conductance anion channel, Maxi-Cl, which plays essential roles in inorganic anion transport, cell volume regulation and release of ATP and glutamate not only in physiological processes but also in pathological processes (PubMed:29046334, PubMed:32442363). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity).|||Membrane http://togogenome.org/gene/10090:Or5an1c ^@ http://purl.uniprot.org/uniprot/Q8VFV8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pld4 ^@ http://purl.uniprot.org/uniprot/Q8BG07 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (PubMed:30111894). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor (PubMed:30111894). Involved in phagocytosis of activated microglia (PubMed:22102906).|||Belongs to the phospholipase D family.|||Deficient mice exhibit a phenotype of chronic activation of the immune system, with splenomegaly marked by elevated levels of interferon-gamma (IFN-gamma) (PubMed:30111894). PDL3 and PLD4 double-deficient mice are unable to survive beyond the age of 21 days due to severe liver inflammation (PubMed:30111894). Livers from double-knockout mice develop lethal hepatic autoinflammatory disease that could be prevented by a single allele of either PDL3 or PLD4 (PubMed:30111894).|||Early endosome|||Endoplasmic reticulum membrane|||Enriched in the white matter of early postnatal brains, as well as in splenic marginal zone cells (PubMed:21085684). Highly expressed in dendritic cells (DCs) and other myeloid cells, with lower expression in B cell (PubMed:30111894).|||Exhibits no phospholipase activity, despite two HKD motifs.|||First detected in cerebellum at postnatal day 0 (P0), increased with age and peaked at P7, and then rapidly decreased to adult levels by P21.|||Highly N-glycosylated.|||Nucleus|||Up-regulated by lipopolysaccharide (LPS) stimulation in microglia (PubMed:22102906). Increased expression in activated microglia and in the demyelinating lesions of adult brain (PubMed:22102906).|||phagosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Klk1b1 ^@ http://purl.uniprot.org/uniprot/P00755 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Traf3 ^@ http://purl.uniprot.org/uniprot/Q3UHJ1|||http://purl.uniprot.org/uniprot/Q60803 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TNF receptor-associated factor family.|||Belongs to the TNF receptor-associated factor family. A subfamily.|||Cytoplasm|||Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in both immune and non-immune cell types (PubMed:17015635). In TLR and RLR signaling pathways, acts as an E3 ubiquitin ligase promoting the synthesis of 'Lys-63'-linked polyubiquitin chains on several substrates such as ASC that lead to the activation of the type I interferon response or the inflammasome (PubMed:19898473, PubMed:23871208, PubMed:26305951, PubMed:23150880). Following the activation of certain TLRs such as TLR4, acts as a negative NF-kappa-B regulator, possibly to avoid unregulated inflammatory response, and its degradation via 'Lys-48'-linked polyubiquitination is required for MAPK activation and production of inflammatory cytokines (PubMed:16306937). Alternatively, when TLR4 orchestrates bacterial expulsion, TRAF3 undergoes 'Lys-33'-linked polyubiquitination and subsequently binds to RALGDS, mobilizing the exocyst complex to rapidly expel intracellular bacteria back for clearance. Acts also as a constitutive negative regulator of the alternative NF-kappa-B pathway, which controls B-cell survival and lymphoid organ development (PubMed:17723217). Required for normal antibody isotype switching from IgM to IgG (PubMed:19228877). Plays a role T-cell dependent immune responses (PubMed:8934568). Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.|||Detected in bone marrow macrophages and spleen B-cells (at protein level). In adult, highest in brain. Also found in kidney, heart, thymus, spleen, lung, muscle, testis and ovary. Not found in liver.|||Endosome|||Homotrimer. Heterotrimer with TRAF2 and TRAF5. Interacts with LTBR/TNFRSF3, TNFRSF4, TNFRSF5/CD40, TNFRSF8/CD30, TNFRSF13C TNFRSF17/BCMA, TLR4 and EDAR. Interacts with MAP3K5, MAP3K14, TRAIP/TRIP, TDP2/TTRAP, TANK/ITRAF and TRAF3IP1. Interaction with TNFRSF5/CD40 is modulated by TANK/ITRAF, which competes for the same binding site. Interacts with TICAM1. Interacts with TRAFD1. Interacts with OTUB1, OTUB2 and OTUD5. Interacts with RNF216, OPTN and TBK1 (By similarity). Identified in a complex with TRAF2, MAP3K14 and BIRC3. Upon exposure to bacterial lipopolysaccharide (LPS), recruited to a transient complex containing TLR4, TRAF3, TRAF6, IKBKG, MAP3K7, MYD88, TICAM1, BIRC2, BIRC3 and UBE2N. Interacts (via RING-type zinc finger domain) with SRC. Interacts with CARD14 (By similarity). Interacts (via MATH domain) with PTPN22; the interaction promotes TRAF3 polyubiquitination (PubMed:23871208). Interacts with MAVS (PubMed:23150880). Directly interacts with DDX3X; this interaction stimulates TRAF3 'Lys-63' ubiquitination (By similarity). Interacts with IRF3 (By similarity). Interacts with IKBKE in the course of viral infection (By similarity). Interacts with TRIM35 (By similarity). Interacts with GAPDH; promoting TRAF3 ubiquitination (By similarity). Interacts with PPP3CA and PPP3CB (PubMed:26029823). Interacts with RALGDS (By similarity). Interacts with FBXO11 (By similarity).|||In the embryo, expressed from 6.5 dpc with highest levels found between 11.5 dpc and 13.5 dpc. At late stages of gestation, from 14.5 dpc, only low levels are detected.|||Mitochondrion|||Newborns appear normal, but do not thrive. Their blood glucose levels and leukocyte levels decrease steadily, the spleen size is dramatically reduced, and they become progressively runted. They die about ten days after birth. Mice exhibit abnormally high MAP3K14 protein levels and constitutive proteolytic processing of NFKB2/p100, leading to constitutive activation of NF-kappa-B.|||The MATH/TRAF domain binds to receptor cytoplasmic domains.|||The Ring-type zinc finger domain is required for its function in down-regulation of NFKB2 proteolytic processing.|||Undergoes 'Lys-48'-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40 (PubMed:19898473). 'Lys-48'-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (PubMed:23334419). Undergoes 'Lys-63'-linked ubiquitination during early stages of virus infection, and 'Lys-48'-linked ubiquitination during later stages. Undergoes both 'Lys-48'-linked and 'Lys-63'-linked ubiquitination in response to TLR3 and TLR4 signaling. 'Lys-63'-linked ubiquitination can be mediated by TRIM35. Deubiquitinated by OTUB1, OTUB2 and OTUD5. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to terminate the pattern-recognition receptors/PRRs pathways (PubMed:26474655). Ubiquitinated at Lys-328 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:23542741).|||Undergoes 'Lys-48'-linked polyubiquitination, leading to its proteasomal degradation in response to signaling by TNFSF13B, TLR4 or through CD40. 'Lys-48'-linked polyubiquitinated form is deubiquitinated by OTUD7B, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Undergoes 'Lys-63'-linked ubiquitination during early stages of virus infection, and 'Lys-48'-linked ubiquitination during later stages. Undergoes both 'Lys-48'-linked and 'Lys-63'-linked ubiquitination in response to TLR3 and TLR4 signaling. 'Lys-63'-linked ubiquitination can be mediated by TRIM35. Deubiquitinated by OTUB1, OTUB2 and OTUD5. Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to terminate the pattern-recognition receptors/PRRs pathways (By similarity). Undergoes also 'Lys-29'-linked ubiquitination on Cys-55 and Cys-123 by NEDD4L; leading to increased 'Lys-48'- and 'Lys-63'-linked ubiquitination as well as increased binding to TBK1. TLR4 signals emanating from bacteria containing vesicles trigger 'Lys-33'-linked polyubiquitination that promotes the assembly of the exocyst complex thereby connecting innate immune signaling to the cellular trafficking apparatus (By similarity). Deubiquitinated by USP25 during viral infection, leading to TRAF3 stabilization and type I interferon production (PubMed:26305951). 'Lys-63'-linked ubiquitination by FBXO11 in a NEDD8-dependent manner promotes the amplification of IFN-I signaling (By similarity). http://togogenome.org/gene/10090:Vmn1r188 ^@ http://purl.uniprot.org/uniprot/Q8K3N2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sdr42e1 ^@ http://purl.uniprot.org/uniprot/Q9D665 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the 3-beta-HSD family.|||Membrane http://togogenome.org/gene/10090:Bbs5 ^@ http://purl.uniprot.org/uniprot/Q9CZQ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BBS5 family.|||Cytoplasm|||PPart of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Binds to phosphoinositides. Interacts with CCDC28B. Interacts with SMO; the interaction is indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO. Interacts with PKD1 (By similarity). Interacts with DLEC1 (By similarity).|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly (By similarity).|||centriolar satellite|||cilium basal body|||cilium membrane http://togogenome.org/gene/10090:Eif4e ^@ http://purl.uniprot.org/uniprot/A0A0G2JFB4|||http://purl.uniprot.org/uniprot/P63073|||http://purl.uniprot.org/uniprot/Q3TK95|||http://purl.uniprot.org/uniprot/Q8C470 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts in the cytoplasm to initiate and regulate protein synthesis and is required in the nucleus for export of a subset of mRNAs from the nucleus to the cytoplasm which promotes processes such as RNA capping, processing and splicing (PubMed:18805096, PubMed:25456498, PubMed:36843541, PubMed:8577715, PubMed:31042468). Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:18805096). This protein recognizes and binds the 7-methylguanosine (m7G)-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (By similarity). Together with EIF4G1, antagonizes the scanning promoted by EIF1-EIF4G1 and is required for TISU translation, a process where the TISU element recognition makes scanning unnecessary (By similarity). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (PubMed:18805096, PubMed:25456498). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap (PubMed:18805096). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (PubMed:25456498). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (By similarity). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). As well as its roles in translation, also involved in mRNA nucleocytoplasmic transport (PubMed:8577715). Its role in mRNA export from the nucleus to the cytoplasm relies on its ability to bind the m7G cap of RNAs and on the presence of the 50-nucleotide EIF4E sensitivity element (4ESE) in the 3'UTR of sensitive transcripts (PubMed:17074885). Interaction with the 4ESE is mediated by LRPPRC which binds simultaneously to both EIF4E and the 4ESE, thereby acting as a platform for assembly for the RNA export complex (PubMed:19262567, PubMed:28325843). EIF4E-dependent mRNA export is independent of ongoing protein or RNA synthesis and is also NFX1-independent but is XPO1-dependent with LRPPRC interacting with XPO1 to form an EIF4E-dependent mRNA export complex (PubMed:17074885). Alters the composition of the cytoplasmic face of the nuclear pore to promote RNA export by reducing RANBP2 expression, relocalizing nucleoporin NUP214 and increasing expression of RANBP1 and RNA export factors DDX19 and GLE1 (PubMed:22902403). Promotes the nuclear export of cyclin CCND1 mRNA (PubMed:8577715, PubMed:15574771, PubMed:11500381, PubMed:18391071). Promotes the nuclear export of NOS2/iNOS mRNA (By similarity). Promotes the nuclear export of MDM2 mRNA (By similarity). Also promotes the export of additional mRNAs, including others involved in the cell cycle (PubMed:17074885). In the nucleus, binds to capped splice factor-encoding mRNAs and stimulates their nuclear export to enhance splice factor production by increasing their cytoplasmic availability to the translation machinery (PubMed:36843541). May also regulate splicing through interaction with the spliceosome in an RNA and m7G cap-dependent manner (PubMed:36843541). Also binds to some pre-mRNAs and may play a role in their recruitment to the spliceosome (PubMed:36843541). Promotes steady-state capping of a subset of coding and non-coding RNAs by mediating nuclear export of capping machinery mRNAs including RNMT, RNGTT and RAMAC to enhance their translation (PubMed:33055213). Stimulates mRNA 3'-end processing by promoting the expression of several core cleavage complex factors required for mRNA cleavage and polyadenylation, and may also have a direct effect through its interaction with the CPSF3 cleavage enzyme (PubMed:31042468). Rescues cells from apoptosis by promoting activation of serine/threonine-protein kinase AKT1 through mRNA export of NBS1 which potentiates AKT1 phosphorylation and also through mRNA export of AKT1 effectors, allowing for increased production of these proteins (PubMed:18391071).|||Belongs to the eukaryotic initiation factor 4E family.|||Cytoplasm|||Nucleus|||Nucleus speckle|||P-body|||Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex (By similarity). Phosphorylation also enhances its mRNA transport function (PubMed:15574771). Phosphorylation at Ser-209 is not essential for protein synthesis (By similarity).|||Stress granule|||eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (By similarity). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3 (PubMed:9200613). EIF4E is also known to interact with other partners (By similarity). Interacts with EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the nucleus (By similarity). Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:10394359). Interacts mutually exclusive with EIF4A1 or EIF4A2 (By similarity). Interacts with NGDN and PIWIL2 (PubMed:16705177, PubMed:19114715). Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1 (PubMed:18805096). Interacts directly with CYFIP1 (PubMed:18805096). Interacts with CLOCK (PubMed:22900038). Binds to MKNK2 in nucleus (By similarity). Interacts with LIMD1, WTIP and AJUBA (By similarity). Interacts with APOBEC3G in an RNA-dependent manner (By similarity). Interacts with LARP1 (By similarity). Interacts with METTL3 (By similarity). Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (By similarity). Interacts with DDX3X; interaction is direct and in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability and is required for the repression of cap-dependent translation and the increase of IRES-mediated translation (By similarity). DDX3X competes with EIF4G1 for interaction with EIF4E (By similarity). Interacts with EIF4G1; which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site (By similarity). Interacts with BTG4 and CNOT7 (PubMed:27065194). Interacts with LRPPRC (via N-terminus); the interaction promotes association of EIF4E with 4ESE-containing mRNAs (PubMed:19262567, PubMed:28325843). Interacts with mRNA cleavage enzyme CPSF3 and its cofactor CPSF1 (PubMed:31042468). Interacts (via RING-type zinc finger) with PML; the interaction results in conformational changes of both interacting proteins and reduces EIF4E affinity for the 5' m7G cap of mRNA, thus reducing EIF4E-mediated mRNA nuclear export (PubMed:11500381, PubMed:11575918). Interacts with homeobox protein HHEX/PRH; the interaction inhibits EIF4E-mediated mRNA nuclear export (PubMed:12554669). Interacts with homeobox protein HOXA9; the interaction positively regulates EIF4E-mediated mRNA nuclear export (PubMed:15657436). Interacts with homeobox protein EMX2 (PubMed:15247416).|||nuclear body http://togogenome.org/gene/10090:Gm21065 ^@ http://purl.uniprot.org/uniprot/Q149W4 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Cndp1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0V0|||http://purl.uniprot.org/uniprot/Q3TMU4|||http://purl.uniprot.org/uniprot/Q8BUG2 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M20A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 2 manganese ions per subunit.|||Catalyzes the peptide bond hydrolysis in Xaa-His dipeptides, displaying the highest activity toward carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-3-methyl-histidine).|||Detected exclusively in kidney.|||Homodimer.|||In contrast to human counterpart, it lacks a signal sequence.|||Secreted http://togogenome.org/gene/10090:Rbm4 ^@ http://purl.uniprot.org/uniprot/Q8C7Q4 ^@ Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates according to a circadian rhythm in the SCN.|||Cytoplasm|||Cytoplasmic granule|||Expressed in the suprachiasmatic nucleus (SCN). Expressed in myocytes; expression gradually increases during muscle cell differentiation (at protein level). Expressed in the suprachiasmatic nucleus (SCN).|||Interacts with TNPO3; the interaction mediates nuclear import of the protein and is disrupted by nuclear Ran bound to GTP. Interacts with EIF4G1 and WT1. Interacts with EIF4A1; the interaction is modulated under stress-induced conditions. Interacts with AGO1. Interacts with AGO2; the interaction occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with DDX5; the interaction occurs in an RNA-independent manner (By similarity).|||May be due to an intron retention.|||Nucleus|||Nucleus speckle|||Phosphorylated. Phosphorylated in vitro on Ser-306 by SRPK1. Phosphorylation on Ser-306 is induced upon cell stress signaling, which alters its subcellular localization and may modulate its activity on IRES-mediated mRNA translation (By similarity). Phosphorylated. Phosphorylation on Ser-306 is induced upon cell muscle differentiation.|||RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5'-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro.|||nucleolus http://togogenome.org/gene/10090:Or4e1 ^@ http://purl.uniprot.org/uniprot/Q9R0K4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp3 ^@ http://purl.uniprot.org/uniprot/Q8BLB0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Adam32 ^@ http://purl.uniprot.org/uniprot/Q8K410 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in sperm (at protein level) (PubMed:20945367). Highly expressed in the testis and weakly expressed in the epididymis, brain and heart (PubMed:12568724).|||Initially expressed in the testis at day 16 and reaches adult expression levels by day 30 after birth.|||May play a role in sperm development and fertilization This is a non-catalytic metalloprotease-like protein.|||Membrane http://togogenome.org/gene/10090:Fmo3 ^@ http://purl.uniprot.org/uniprot/P97501|||http://purl.uniprot.org/uniprot/Q3UEN4|||http://purl.uniprot.org/uniprot/Q8C7J1 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds. Plays an important role in the metabolism of trimethylamine (TMA), via the production of trimethylamine N-oxide (TMAO) metabolite. TMA is generated by the action of gut microbiota using dietary precursors such as choline, choline containing compounds, betaine or L-carnitine. By regulating TMAO concentration, FMO3 directly impacts both platelet responsiveness and rate of thrombus formation.|||Expression is specifically repressed in male mice after puberty, preventing trimethylamine degradation. Trimethylamine is present at high concentration in the urine of male mice after puberty and acts as an attractant.|||Liver.|||Membrane|||Microsome membrane|||Trimethylamine is a bacterial metabolite found in some animal odors, and is a repulsive odor associated with bad breath and spoiled food for most organisms, except for M.musculus, where it acts as an attractant. http://togogenome.org/gene/10090:Gabrr2 ^@ http://purl.uniprot.org/uniprot/P56476 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRR2 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission (By similarity).|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1 (By similarity).|||Isoform 2 could be translated from an upstream initiator ATG located in frame within the first coding exon. The probability of a signal peptide within this isoform is very low.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Zfp148 ^@ http://purl.uniprot.org/uniprot/Q61624 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Detected in embryos from 7 dpc to 17 dpc. Expression decreases in developing skeletal muscles.|||Interacts with HNRNPDL (By similarity). Interacts with the 5FMC complex; the interaction requires association with CHTOP (PubMed:22872859). Interacts with CAVIN1 (PubMed:10727401).|||Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes.|||Nucleus|||Strong expression detected in brain, lung, liver and kidney, with lower levels detected in spleen, skeletal muscle, testis and heart.|||Sumoylated with SUMO2. Desumoylated by SENP3, resulting in the stimulation of transcription of its target genes. http://togogenome.org/gene/10090:Kntc1 ^@ http://purl.uniprot.org/uniprot/Q8C3Y4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (By similarity).|||Interacts with ZW10. This interaction is required for stable association with the kinetochore. Component of the RZZ complex composed of KNTC1/ROD, ZW10 and ZWILCH (By similarity).|||Nucleus|||kinetochore|||spindle http://togogenome.org/gene/10090:Casp8ap2 ^@ http://purl.uniprot.org/uniprot/Q9WUF3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in heart, brain, thymus, lung, testis and spleen.|||Mitochondrion|||Nucleus|||PML body|||Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation (By similarity). Required for histone gene transcription and progression through S phase (By similarity). Required for histone gene transcription and S phase progression (By similarity). Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis.|||Self-associates. Interacts with NPAT (By similarity). Interacts with SRRT (By similarity). Interacts (via SIM domains) with SUMO1 and SUMO2 (By similarity). Interacts with SP100; may negatively regulate CASP8AP2 export from the nucleus to the cytoplasm (By similarity). Interacts with NCOA2 and NCOA3 (By similarity). Component of the death-inducing signaling complex (DISC) with CASP8, FADD and FAS. Interacts with TRAF2. http://togogenome.org/gene/10090:Fam131c ^@ http://purl.uniprot.org/uniprot/A2ADB2 ^@ Similarity ^@ Belongs to the FAM131 family. http://togogenome.org/gene/10090:Tmem215 ^@ http://purl.uniprot.org/uniprot/A7E1Z1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Asb11 ^@ http://purl.uniprot.org/uniprot/Q9CQ31 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Bend3 ^@ http://purl.uniprot.org/uniprot/Q6PAL0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homooligomer, probably a homooctamer. Interacts with HDAC2 and HDAC3, but not HDAC1. Interacts with SALL4. Interacts with SMARCA5/SNF2H, BAZ2A/TIP5 and USP21 (By similarity). Interacts with the nucleosome remodeling and histone deacetylase (NuRD) repressor complex (PubMed:25457167). Interacts (via BEN domains 1 and 3) with ERCC6L (via N-terminal TPR repeat); the interaction is direct (By similarity).|||Nucleus|||Sumoylated at Lys-20 by SUMO1 and at Lys-509 by SUMO1, SUMO2 and SUMO3. Sumoylation probably occurs sequentially, with that of Lys-20 preceding that of Lys-509. It does not alter association with heterochromatin, but is required for the repression of transcription.|||The BEN domain 4 is necessary and sufficient for the localization of BEND3 to heterochromatic regions.|||Transcriptional repressor which associates with the NoRC (nucleolar remodeling complex) complex and plays a key role in repressing rDNA transcription. The sumoylated form modulates the stability of the NoRC complex component BAZ2A/TIP5 by controlling its USP21-mediated deubiquitination (By similarity). Binds to unmethylated major satellite DNA and is involved in the recruitment of the Polycomb repressive complex 2 (PRC2) to major satellites (PubMed:25457167). Stimulates the ERCC6L translocase and ATPase activities (By similarity).|||nucleolus http://togogenome.org/gene/10090:Gtf2h2 ^@ http://purl.uniprot.org/uniprot/Q7TPV0|||http://purl.uniprot.org/uniprot/Q9JIB4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTF2H2 family.|||Component of the TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2 and ERCC3. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with XPB, XPD, GTF2H1 and GTF2H3.|||Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. The N-terminus of GTF2H2 interacts with and regulates XPD whereas an intact C-terminus is required for a successful escape of RNAP II form the promoter.|||Nucleus http://togogenome.org/gene/10090:Hectd1 ^@ http://purl.uniprot.org/uniprot/F8WIE5 ^@ Function|||Similarity ^@ Belongs to the UPL family. K-HECT subfamily.|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. http://togogenome.org/gene/10090:Mindy1 ^@ http://purl.uniprot.org/uniprot/B7ZMR0|||http://purl.uniprot.org/uniprot/Q76LS9 ^@ Function|||Sequence Caution|||Similarity ^@ Belongs to the MINDY deubiquitinase family. FAM63 subfamily.|||Contaminating sequence. Potential vector sequence.|||Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins. Has exodeubiquitinase activity and has a preference for long polyubiquitin chains. May play a regulatory role at the level of protein turnover. http://togogenome.org/gene/10090:Pabir2 ^@ http://purl.uniprot.org/uniprot/G1UD78|||http://purl.uniprot.org/uniprot/Q6NZE7 ^@ Similarity ^@ Belongs to the FAM122 family. http://togogenome.org/gene/10090:Pcid2 ^@ http://purl.uniprot.org/uniprot/Q8BFV2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CSN12 family.|||Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153 (By similarity). Interacts with BRCA2 (By similarity). Interacts with SRCAP chromatin remodeling complex component ZNHIT1; the interaction results in inhibition of SRCAP complex activity, preventing the deposition of histone variant H2AZ1/H2A.Z to lymphoid fate regulator genes and restricting lymphoid lineage commitment (PubMed:29138493).|||Conditional knockout in bone marrow increases lymphoid cell numbers but decreases the number of myeloid cells (PubMed:29138493). Decreased bone marrow cellularity, enlargement of thymus and cervical lymph nodes with an increased number of lymphocytes, increased lymphocyte numbers in peripheral blood, decreased numbers of granulocytes and monocytes, enrichment of transcription factor Spi1/PU.1 at the promoters of lymphoid fate regulator genes, increased expression of lymphoid fate regulator genes, and enhanced lymphoid differentiation of hematopoietic multipotent progenitor cells (PubMed:29138493). No effect on red blood cell or platelet numbers (PubMed:29138493).|||Cytoplasm|||Highly expressed in bone marrow and haematopoietic progenitor cells but is almost undetectable in mature blood cells.|||In B lineage cells, expressed in a stage-dependent manner at high levels in bone marrow pre-B and immature B-cells, and in spleen transitional 1 and follicular B-cells, but at lower levels in pro-B, transitional 2, and marginal zone B-cells.|||Required for B-cell survival through the regulation of the expression of cell-cycle checkpoint MAD2L1 protein during B cell differentiation (PubMed:20870947). As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (By similarity). Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and transcription-associated genomic instability (By similarity). Blocks the activity of the SRCAP chromatin remodeling complex by interacting with SRCAP complex member ZNHIT1 and inhibiting its interaction with the complex (PubMed:29138493). This prevents the deposition of histone variant H2AZ1/H2A.Z at the nucleosomes of key lymphoid fate regulator genes which suppresses their expression and restricts lymphoid lineage commitment (PubMed:29138493).|||nuclear pore complex http://togogenome.org/gene/10090:Mlxipl ^@ http://purl.uniprot.org/uniprot/Q99MZ3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA as a heterodimer with TCFL4/MLX.|||Expressed in the ventricular and intermediate zones of the developing spinal cord of 12.5 dpc embryos. In later embryos expressed in a variety of tissues.|||Nucleus|||Phosphorylation at Ser-566 by AMPK inactivates the DNA-binding activity.|||Transcriptional repressor. Binds to the canonical and non-canonical E box sequences 5'-CACGTG-3'. http://togogenome.org/gene/10090:Hoxb4 ^@ http://purl.uniprot.org/uniprot/P10284 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family. Deformed subfamily.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Cenpe ^@ http://purl.uniprot.org/uniprot/E9QKK1|||http://purl.uniprot.org/uniprot/Q6RT24 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Contaminating sequence. Potential poly-A sequence.|||Expressed in hippocampus. Also detected in liver and fibroblasts (at protein level).|||Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules. The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated. Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends. Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized (By similarity). Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules (PubMed:12925705). The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC (PubMed:12361599). Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss (PubMed:12925705).|||Monomer. Interacts with CENPF, SEPT7 KIF18A and PRC1 (By similarity). Interacts with BUB1B (PubMed:12925705). Interacts with SKAP; this interaction greatly favors SKAP binding to microtubules. Interacts with TRAPPC12 and CTCF (By similarity).|||Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association to the kinetochore.|||The C-terminal inhibitory domain is phosphorylated. Phosphorylation relieves autoinhibition of the kinetochore motor (By similarity).|||The protein is composed of a N-terminal kinesin-motor domain involved in the chromosome movements, a long coil-coiled region involved in the homodimerization and an inhibitory C-tail involved in autoinhibition of the N-terminal catalytic part.|||centromere|||kinetochore|||spindle http://togogenome.org/gene/10090:Or9g19 ^@ http://purl.uniprot.org/uniprot/Q7TR96 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Spta1 ^@ http://purl.uniprot.org/uniprot/P08032 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the spectrin family.|||Composed of non-homologous chains, alpha and beta, which aggregate to form dimers, tetramers, and higher polymers. Interacts with FASLG (By similarity).|||Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane.|||This complex is anchored to the cytoplasmic face of the plasma membrane via another protein, ankyrin, which binds to beta-spectrin and mediates the binding of the whole complex to a transmembrane protein band 3. The interaction of erythrocyte spectrin with other proteins through specific binding domains lead to the formation of an extensive subplasmalemmal meshwork which is thought to be responsible for the maintenance of the biconcave shape of human erythrocytes, for the regulation of plasma membrane components and for the maintenance of the lipid asymmetry of the plasma membrane.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Or2ak4 ^@ http://purl.uniprot.org/uniprot/A0A0N4SVP2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ica1 ^@ http://purl.uniprot.org/uniprot/P97411 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ 129/SvJ mice lacking Ica1 do not display an obvious phenotype and age normally, while NOD mice without Ica1 develop diabetes and display sudden mid-life lethality but are resistant to cyclophosphamide-induced disease acceleration.|||Golgi apparatus membrane|||May play a role in neurotransmitter secretion.|||Predominantly expressed in brain, pancreas and stomach mucosa. High expression also found in stomach muscle and testis.|||cytosol|||secretory vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Or2z9 ^@ http://purl.uniprot.org/uniprot/E9Q4J3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hsd17b4 ^@ http://purl.uniprot.org/uniprot/P51660 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Bifunctional enzyme acting on the peroxisomal fatty acid beta-oxidation pathway (PubMed:17442273). Catalyzes two of the four reactions in fatty acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3-hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is further metabolized by SCPx. Can use straight-chain and branched-chain fatty acids, as well as bile acid intermediates as substrates (By similarity) (PubMed:17442273).|||Homodimer.|||Peroxisome|||Present in many tissues with highest concentrations in liver and kidney.|||The protein is found both as a full-length peptide and in a cleaved version. http://togogenome.org/gene/10090:Spx ^@ http://purl.uniprot.org/uniprot/A0A1C7CYU9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the spexin family.|||Secreted http://togogenome.org/gene/10090:T ^@ http://purl.uniprot.org/uniprot/P20293|||http://purl.uniprot.org/uniprot/Q78ZW9 ^@ Caution|||Developmental Stage|||Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit ^@ During gastrula and neurula stages in involuting mesoderm and in the notochord.|||Embryo lacking the T gene fail to form the notochord, the entire posterior region and the allantois, and die at about 10 days of gestation.|||Involved in the transcriptional regulation of genes required for mesoderm formation and differentiation (PubMed:7588606). Binds to a palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence and activates gene transcription when bound to such a site (PubMed:8344258, PubMed:7588606).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Monomer. Binds DNA as a monomer.|||Nucleus http://togogenome.org/gene/10090:Gng14 ^@ http://purl.uniprot.org/uniprot/B2RVA4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units; alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||Membrane http://togogenome.org/gene/10090:Actn1 ^@ http://purl.uniprot.org/uniprot/A1BN54|||http://purl.uniprot.org/uniprot/Q7TPR4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-actinin family.|||Cell junction|||Cell membrane|||F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (By similarity).|||Homodimer; antiparallel. Interacts with MYOZ2, TTID and LPP. Interacts with DDN (By similarity). Interacts with PSD (PubMed:17298598). Interacts with MICALL2 (PubMed:23100251). Interacts with DNM2 and CTTN. Interacts with PDLIM1. Interacts with PDLIM2. Interacts with PDLIM4 (via PDZ domain) (By similarity).|||Z line|||cytoskeleton|||ruffle http://togogenome.org/gene/10090:Or4d2b ^@ http://purl.uniprot.org/uniprot/Q5SW50 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Maml3 ^@ http://purl.uniprot.org/uniprot/D4QGC2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mastermind family.|||Nucleus speckle http://togogenome.org/gene/10090:Pdlim2 ^@ http://purl.uniprot.org/uniprot/Q8R1G6 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in lung. Expressed at intermediate level in kidney, testis and spleen. Weakly expressed in heart and brain.|||Interacts with alpha-actinins ACTN1 and ACTN4, FLNA and MYH9 (By similarity). Interacts (via LIM zinc-binding domain) with MKRN2 (PubMed:28378844).|||Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity (By similarity).|||Regulated by IGF-1.|||cytoskeleton http://togogenome.org/gene/10090:Twf1 ^@ http://purl.uniprot.org/uniprot/Q91YR1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles.|||Belongs to the actin-binding proteins ADF family. Twinfilin subfamily.|||Cytoplasm|||Expression was widespread throughout the embryonic stages analyzed; 10.5 dpc, 12.5 dpc, 14.5 dpc and 18.5 dpc. At 14.5 dpc, strongest expression was observed in the developing central and peripheral nervous system (CNS and PNS, respectively) and in the olfactory sensory epithelium. In the CNS, the proliferating neuronal precursors in the ventricular zone expressed it more than the postmitotic neurons. At 18.5 dpc, highest expression levels were detected in the mechanosensory hair cells of the inner ear and in the differentiated keratinocytes of the skin.|||Interacts with G-actin; ADP-actin form and capping protein (CP) (PubMed:12807912, PubMed:15282541, PubMed:16511569). May also be able to interact with TWF2 and phosphoinositides, PI(4,5)P2 (PubMed:12807912). When bound to PI(4,5)P2, it is down-regulated (PubMed:12807912). Interacts with ACTG1 (By similarity).|||Phosphorylated on serine and threonine residues.|||Widely expressed with highest levels in brain, liver and kidney. Also expressed in heart, lung and testis. Not detected in spleen or skeletal muscle.|||cytoskeleton http://togogenome.org/gene/10090:Rab12 ^@ http://purl.uniprot.org/uniprot/P35283 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Golgi apparatus membrane|||Interacts with RABIF and OPTN (PubMed:23357852). Interacts with LRRK2; interaction facilitates phosphorylation of Ser-105 (By similarity). Interacts with GDI1, GDI2, CHM and CHML; these interactions are disrupted by phosphorylation on Ser-105 (By similarity). Interacts with RILPL1 and RILPL2; these interactions are dependent on phosphorylation of Ser-105 (By similarity).|||Lysosome membrane|||Phosphorylation of Ser-105 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). That Rab is activated by DENND3, a guanine exchange factor.|||Recycling endosome membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab may play a role in protein transport from recycling endosomes to lysosomes regulating, for instance, the degradation of the transferrin receptor. Involved in autophagy.|||Ubiquitously expressed.|||autophagosome http://togogenome.org/gene/10090:Pex7 ^@ http://purl.uniprot.org/uniprot/B7ZNK8|||http://purl.uniprot.org/uniprot/P97865 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat peroxin-7 family.|||Interacts with PEX5; interaction only takes place when PEX7 is associated with cargo proteins (By similarity). Interacts with VWA8 (By similarity).|||Mice were born alive, but display a variable degree of dwarfism and hypotonia with decreased motility, hampering their feeding (PubMed:12915479). Perinatal lethality is frequent, although some mice survive beyond 18 months (PubMed:12915479). In the intermediate zone of the developing cerebral cortex, increased neuronal density is observed (PubMed:12915479). Increased neuronal density is caused by defects in neuronal migration (PubMed:12915479). Mice also show defects in ossification of distal bone elements of the limbs as well as parts of the skull and vertebrae (PubMed:12915479). Cells display normal peroxisome assembly, but show impaired peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal (PubMed:12915479). Biochemically, cells show severe depletion of plasmalogens, impaired alpha-oxidation of phytanic acid and impaired beta-oxidation of very-long-chain fatty acids (PubMed:12915479).|||Peroxisome matrix|||Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal (PubMed:9090381, PubMed:12915479). Specifically binds to cargo proteins containing a PTS2 peroxisomal targeting signal in the cytosol (By similarity). Cargo protein-binding triggers interaction with PEX5 and formation of a ternary complex composed of PEX5 and PEX7 along with PTS2-containing cargo proteins, which is tranlocated into peroxisomes by passing through the PEX13-PEX14 docking complex (By similarity).|||cytosol http://togogenome.org/gene/10090:Alg12 ^@ http://purl.uniprot.org/uniprot/Q8VCA2|||http://purl.uniprot.org/uniprot/Q8VDB2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Adds the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation.|||Belongs to the glycosyltransferase 22 family.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Fsd1l ^@ http://purl.uniprot.org/uniprot/Q8BYN5 ^@ Miscellaneous ^@ Due to intron retention. http://togogenome.org/gene/10090:H2ac11 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Shmt2 ^@ http://purl.uniprot.org/uniprot/Q9CZN7 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SHMT family.|||Catalyzes the cleavage of serine to glycine accompanied with the production of 5,10-methylenetetrahydrofolate, an essential intermediate for purine biosynthesis (By similarity). Serine provides the major source of folate one-carbon in cells by catalyzing the transfer of one carbon from serine to tetrahydrofolate (By similarity). Contributes to the de novo mitochondrial thymidylate biosynthesis pathway via its role in glycine and tetrahydrofolate metabolism: thymidylate biosynthesis is required to prevent uracil accumulation in mtDNA (By similarity). Also required for mitochondrial translation by producing 5,10-methylenetetrahydrofolate; 5,10-methylenetetrahydrofolate providing methyl donors to produce the taurinomethyluridine base at the wobble position of some mitochondrial tRNAs (PubMed:29452640). Associates with mitochondrial DNA (By similarity). In addition to its role in mitochondria, also plays a role in the deubiquitination of target proteins as component of the BRISC complex: required for IFNAR1 deubiquitination by the BRISC complex (By similarity).|||Cytoplasm|||Embryonic lethality after 13.5 days post coitum (dpc) due to mitochondrial respiration defects and retardation of cell growth. Mitochondrial respiration defects are due to reduction of mitochondrial translation.|||Homotetramer; in the presence of bound pyridoxal 5'-phosphate. Homodimer; in the absence of bound pyridoxal 5'-phosphate. Pyridoxal 5'-phosphate binding mediates an important conformation change that is required for tetramerization. Interacts with ABRAXAS2; the interaction is direct. Identified in a complex with ABRAXAS2 and the other subunits of the BRISC complex, at least composed of the ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with ABRAXAS2 and IFNAR1. Interacts with KIRREL3.|||Hydroxymethyltransferase is inhibited by succinylation at Lys-280.|||In eukaryotes there are two forms of the enzymes: a cytosolic one and a mitochondrial one.|||Mitochondrion|||Mitochondrion inner membrane|||Nucleus|||Present in the placenta, brain and liver during embryonic development (at protein level).|||Succinylation at Lys-280 inhibits the hydroxymethyltransferase activity. Desuccinylation by SIRT5 restores the activity, leading to promote cell proliferation.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Isl2 ^@ http://purl.uniprot.org/uniprot/Q0VAX2|||http://purl.uniprot.org/uniprot/Q9CXV0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with LHX4.|||Nucleus|||Transcriptional factor that defines subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways. http://togogenome.org/gene/10090:Dennd5a ^@ http://purl.uniprot.org/uniprot/A0A0R4J1B6|||http://purl.uniprot.org/uniprot/Q6PAL8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAB6IP1 family.|||Golgi apparatus membrane|||Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity). Involved in the negative regulation of neurite outgrowth (By similarity).|||Interacts with RAB6A bound to GTP.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Pifo ^@ http://purl.uniprot.org/uniprot/Q9D9W1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 7.75 dpc, expression restricted to the ventral node monociliated pit cells. Not expressed in other tissues at detectable levels until 9.5 dpc. At 10.5 dpc, expressed in motor neurons in the ventral neural tube and in the apical ectodermal ridge of lim buds.|||Cytoplasm|||Cytoplasmic vesicle|||During primary cilia disassembly, involved in cilia disassembly. Required specifically to control cilia retraction as well as the liberation and duplication of the basal body/centrosome. May act by stimulating AURKA activity at the basal body in a cell cycle-dependent manner.|||Expressed in tissues rich in ciliated cells, such as lung, kidney, vas deferens and testis. Both isoforms 1 and 2 are expressed in testis.|||Golgi stack|||Interacts with proteins involved in ciliary transport, including ARL13B, CETN1, KIF3A, RAB6A, RAB8A, TUBB1 and TUBG1. Interacts with AURKA.|||Nucleus|||trans-Golgi network http://togogenome.org/gene/10090:Ntrk3 ^@ http://purl.uniprot.org/uniprot/A0A0A6YWF9|||http://purl.uniprot.org/uniprot/Q6VNS1 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures (By similarity). Binds SH2B2. Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts with PTPRS (PubMed:25385546).Interacts with MAPK8IP3/JIP3 (By similarity).|||Expression oscillates in a circadian manner in the liver.|||Isoform 2 expression is restricted to specific areas in adult brain. Isoform 3 transcripts are readily detected early during embryogenesis and are expressed predominantly in adult brain and gonads.|||Ligand-mediated auto-phosphorylation.|||Membrane|||Non-catalytic.|||Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. http://togogenome.org/gene/10090:Ssxb10 ^@ http://purl.uniprot.org/uniprot/Q6XAR7 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Rbm7 ^@ http://purl.uniprot.org/uniprot/Q9CQT2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the nuclear exosome targeting (NEXT) complex composed of MTREX, ZCCHC8, and RBM7 that directs a subset of non-coding short-lived RNAs for exosomal degradation (PubMed:25525152). Interacts with ZCCHC8 and SF3B2/SAP145. Binds to MTREX through ZCCHC8. Interacts with YWHAE and YWHAZ; these interactions are stress-dependent and RBM7 phosphorylation dependent; release RNA from the NEXT complex and may affect RNA targeting to the nuclear RNA exosomome for degradation. Interacts with MEPCE and LARP7, the core subunits of 7SK snRNP; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core and P-TEFb complex activation (By similarity).|||Nucleus|||Phosphorylated at Ser-136 by MAPK14/p38-alpha-activated MAPKAPK2/MK2; this phosphorylation is stress-dependent; this phosphorylation decreases its RNA-binding capacity therefore affecting RNA nuclear exosome-mediated degradation (PubMed:25525152). This phosphorylation mediates YWHAE and YWHAZ interactions (By similarity).|||RNA-binding subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs. Binds preferentially polyuridine sequences and associates with newly synthesized RNAs, including pre-mRNAs and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from small nuclear RNAs (snRNAs). Participates in several biological processes including DNA damage response (DDR) and stress response. During stress response, activation of the p38MAPK-MK2 pathway decreases RBM7-RNA-binding and subsequently the RNA exosome degradation activities, thereby modulating the turnover of non-coding transcriptome. Participates in DNA damage response (DDR), through its interaction with MEPCE and LARP7, the core subunits of 7SK snRNP complex, that release the positive transcription elongation factor b (P-TEFb) complex from the 7SK snRNP. In turn, activation of P-TEFb complex induces the transcription of P-TEFb-dependent DDR genes to promote cell viability.|||The RRM domain mediates RNA binding; the RNA must have four nucleotides for efficient binding. Mediates the interaction of NEXT complex with promoter upstream transcripts (PROMPTs) and potentially aberrant forms of other non coding RNAs, such as snRNAs. The RRM domain exhibits specificity for polyuridine sequences.|||nucleoplasm http://togogenome.org/gene/10090:Fem1c ^@ http://purl.uniprot.org/uniprot/Q8CEF1 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the fem-1 family.|||Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1C.|||Insertion of the beta Geo promoter trap into the Fem1c gene is the cause of ROSA3 mice (PubMed:15082774). Adult ROSA3 mice exhibit widespread expression of the trap gene in epithelial cells found in most organs (PubMed:15082774). Although normal processing of the Fem1c transcript is disrupted in homozygous ROSA3 mice, some tissues show low levels of a partially processed transcript containing exons 2 and 3, which contain the entire coding region of Fem1c (PubMed:15082774). ROSA3 mice show no adverse effects in their sexual development or fertility or in the attenuation of neuronal cell death (PubMed:15082774).|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(FEM1C) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2, leading to their ubiquitination and degradation. The CRL2(FEM1C) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding.|||The first seven ANK repeats at the N-terminus (1-242) are essnetial for recognition of Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons.|||Widely expressed. Expressed at higher level in testis. http://togogenome.org/gene/10090:Rbm44 ^@ http://purl.uniprot.org/uniprot/Q3V089 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of intercellular bridges during meiosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells. Not required for fertility.|||Cytoplasm|||Highly expressed in testis. Also expressed in other tissues at lower level.|||Homodimer. Interacts with TEX14.|||No visible phenotype. Null male mice produce an increased number of sperm and show enhanced fertility.|||Present in testes beginning at postnatal day 5 (at protein level). http://togogenome.org/gene/10090:Mapk11 ^@ http://purl.uniprot.org/uniprot/Q9WUI1 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation on threonine and tyrosine by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 induced by environmental stress. HDAC3 interacts directly and selectively with MAPK11 to repress ATF2 transcriptional activity, and regulate TNF gene expression in LPS-stimulated cells. Inhibited by SB203580 and pyridinyl-imidazole related compounds.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Cytoplasm|||Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6, which activates the enzyme.|||Interacts with HDAC3 and DUSP16.|||Nucleus|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK11 functions are mostly redundant with those of MAPK14. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment.|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. http://togogenome.org/gene/10090:Hsbp1 ^@ http://purl.uniprot.org/uniprot/Q9CQZ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HSBP1 family.|||Homohexamer. Associates with heptad repeats of HSF1 trimers and probably also HSF1 monomers, and with HSP70. Association with HSF1 trimers and HSP70 coincides with attenuation of heat shock response and the conversion of HSF1 trimer to monomer (By similarity).|||Negative regulator of the heat shock response. Negatively affects HSF1 DNA-binding activity. May have a role in the suppression of the activation of the stress response during the aging process (By similarity).|||Nucleus http://togogenome.org/gene/10090:Sf3a1 ^@ http://purl.uniprot.org/uniprot/Q3TVM1|||http://purl.uniprot.org/uniprot/Q8K4Z5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of splicing factor SF3A which is composed of three subunits; SF3A3/SAP61, SF3A2/SAP62 and SF3A1/SAP114. SF3A1 functions as scaffold that interacts directly with both SF3A2 and SF3A3. SF3A associates with the splicing factor SF3B and a 12S RNA unit to form the mature 17S U2 small nuclear ribonucleoprotein complex (17S U2 snRNP). Identified in the spliceosome 'E' complex, a precursor of the spliceosome 'A' complex. Identified in the spliceosome 'A' and 'B' complexes. Identified in the spliceosome 'C' complex.|||Involved in pre-mRNA splicing as a component of the splicing factor SF3A complex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex. Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes.|||Nucleus|||Nucleus speckle|||SURP motif 2 mediates direct binding to SF3A3. http://togogenome.org/gene/10090:Vmn1r252 ^@ http://purl.uniprot.org/uniprot/K9J7G4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zeb2 ^@ http://purl.uniprot.org/uniprot/Q3URW5|||http://purl.uniprot.org/uniprot/Q9R0G7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family.|||Chromosome|||Interacts with CBX4 and CTBP1 (By similarity). Binds activated SMAD1, activated SMAD2 and activated SMAD3; binding with SMAD4 is not detected (By similarity).|||Nucleus|||Sumoylation on Lys-391 and Lys-866 is promoted by the E3 SUMO-protein ligase CBX4, and impairs interaction with CTBP1 and transcription repression activity.|||Transcriptional inhibitor that binds to DNA sequence 5'-CACCT-3' in different promoters. Represses transcription of E-cadherin. Represses expression of MEOX2. http://togogenome.org/gene/10090:Fbxo41 ^@ http://purl.uniprot.org/uniprot/Q6NS60 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Crisp3 ^@ http://purl.uniprot.org/uniprot/Q03402 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRISP family.|||By androgens.|||Exponential increase between days 25 and 30 after birth.|||Expressed in submandibular gland.|||Interacts with A1BG (By similarity). Interacts with KNG1 isoform LMW.|||This protein is supposed to help spermatozoa undergo functional maturation while they move from the testis to the ductus deferens.|||secretory vesicle http://togogenome.org/gene/10090:Tex54 ^@ http://purl.uniprot.org/uniprot/G3UW99 ^@ Tissue Specificity ^@ Expressed in Testis. http://togogenome.org/gene/10090:Csnk2a1 ^@ http://purl.uniprot.org/uniprot/Q60737 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.|||Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome.|||Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (By similarity). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (By similarity). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (By similarity). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage (By similarity). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation (By similarity). Can also negatively regulate apoptosis (PubMed:18467326). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:18467326). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:18467326). Phosphorylates YY1, protecting YY1 from cleavage by CASP7 during apoptosis (By similarity). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (By similarity). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB (By similarity). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (By similarity). Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90 (By similarity). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:10806215). Acts as an ectokinase that phosphorylates several extracellular proteins (By similarity). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (By similarity). Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (By similarity). Plays an important role in the circadian clock function by phosphorylating BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (By similarity). Phosphorylates FMR1, promoting FMR1-dependent formation of a membraneless compartment (By similarity).|||Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization (By similarity).|||Embryonic lethality at 10.5 dpc.|||Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation (By similarity). Interacts with RNPS1 (By similarity). Interacts with SNAI1 (PubMed:19923321). Interacts with PML and CCAR2 (By similarity).|||Nucleus|||Phosphorylated at Thr-344, Thr-360, Ser-362 and Ser-370 by CDK1 in prophase and metaphase and dephosphorylated during anaphase. Phosphorylation does not directly affect casein kinase 2 activity, but may contribute to its regulation by forming binding sites for interacting proteins and/or targeting it to different compartments (By similarity). http://togogenome.org/gene/10090:Il17b ^@ http://purl.uniprot.org/uniprot/Q9QXT6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-17 family.|||Secreted|||Stimulates the release of tumor necrosis factor alpha and IL-1-beta from the monocytic cell line THP-1. http://togogenome.org/gene/10090:Eid2b ^@ http://purl.uniprot.org/uniprot/E9Q2Y0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ercc1 ^@ http://purl.uniprot.org/uniprot/E9PUM0|||http://purl.uniprot.org/uniprot/P07903 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ERCC1/RAD10/SWI10 family.|||Heterodimer composed of ERCC1 and ERRC4/XPF (By similarity). Interacts with USP4 (By similarity).|||Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5'-incision during DNA repair. Responsible, in conjunction with SLX4, for the first step in the repair of interstrand cross-links (ICL). Participates in the processing of anaphase bridge-generating DNA structures, which consist in incompletely processed DNA lesions arising during S or G2 phase, and can result in cytokinesis failure. Also required for homology-directed repair (HDR) of DNA double-strand breaks, in conjunction with SLX4 (By similarity).|||Nucleus|||Ubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Deubiquitinated by USP45. http://togogenome.org/gene/10090:Cstf1 ^@ http://purl.uniprot.org/uniprot/Q99LC2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer (By similarity). The CSTF complex is composed of CSTF1 (50 kDa subunit), CSTF2 (64 kDa subunit) and CSTF3 (77 kDa subunit) (By similarity). Interacts (via repeats WD) directly with CSTF3 (By similarity). Interacts (via repeat WD6) with BARD1 (By similarity). Interacts with ERCC6 (By similarity).|||N-terminus mediates homodimerization.|||Nucleus|||One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs (By similarity). May be responsible for the interaction of CSTF with other factors to form a stable complex on the pre-mRNA (By similarity). http://togogenome.org/gene/10090:Or9i2 ^@ http://purl.uniprot.org/uniprot/Q8VFQ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bex3 ^@ http://purl.uniprot.org/uniprot/Q9WTZ9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BEX family.|||May be a signaling adapter molecule involved in NGFR/p75NTR-mediated apoptosis induced by NGF (PubMed:10764727). Plays a role in zinc-triggered neuronal death (PubMed:10764727). In absence of reductive stress, acts as a pseudosubstrate for the CRL2(FEM1B) complex: associates with FEM1B via zinc, thereby preventing association between FEM1B and its substrates (PubMed:34562363).|||Nucleus|||Self-associates (PubMed:11830582). Binds to the DEATH domain of p75NTR/NGFR (PubMed:11830582). Interacts with 14-3-3 epsilon (YWHAE) (PubMed:11278287). Interacts with DIABLO/SMAC (PubMed:15178455).|||The histidine cluster (His cluster) and Cys-121 mediate zinc-binding.|||The nuclear export signal is required for export from the nucleus and the interactions with itself and NGFR/p75NTR.|||Ubiquitinated (PubMed:10764727). Degraded by the proteasome (PubMed:10764727).|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Gm16513 ^@ http://purl.uniprot.org/uniprot/D3YUJ6 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Rbm11 ^@ http://purl.uniprot.org/uniprot/Q80YT9 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer.|||Nucleus speckle|||Peaks perinatally in brain and cerebellum, and at puberty in testis, in concomitance with differentiation events occurring in neurons and germ cells.|||Selectively expressed in brain, cerebellum and testis, and to a lower extent in kidney.|||Tissue-specific splicing factor with potential implication in the regulation of alternative splicing during neuron and germ cell differentiation. Antagonizes SRSF1-mediated BCL-X splicing. May affect the choice of alternative 5' splice sites by binding to specific sequences in exons and antagonizing the SR protein SRSF1 (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Rab31 ^@ http://purl.uniprot.org/uniprot/Q921E2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Detected in brain astrocytes (at protein level).|||Early endosome|||Interacts with OCRL. Interacts (in GDP-bound form) with RIN3 and GAPVD1, which function as guanine exchange factors (GEF). Interacts with EGFR (By similarity). Interacts with NGFR. Interacts (in GTP-bound form) with EEA1. Interacts (in GTP-bound form) with APPL2; interaction contributes to or enhances recruitment of APPL2 to the phagosomes; interaction enhances Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (PubMed:25568335).|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Required for the integrity and for normal function of the Golgi apparatus and the trans-Golgi network. Plays a role in insulin-stimulated translocation of GLUT4 to the cell membrane. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and Mycobacterium (By similarity). Plays a role in M6PR transport from the trans-Golgi network to endosomes. Plays a role in the internalization of EGFR from the cell membrane into endosomes.|||phagosome|||phagosome membrane|||trans-Golgi network|||trans-Golgi network membrane http://togogenome.org/gene/10090:H2al2a ^@ http://purl.uniprot.org/uniprot/Q9CQ70 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although related to histone H2AB1 in human (AC P0C5Y9), it is unclear whether human and mouse H2AB1 proteins are involved in similar processes. In mouse, histone H2AB1 is specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells during spermatogenesis (PubMed:28366643). It is however unclear whether human protein, which participates in mRNA processing and is associated with active transcription, is also involved in nucleosomes to protamine replacement.|||Atypical histone H2A which replaces conventional H2A during late spermatogenesis and is involved in the replacement of histones to protamine in male germ cells (PubMed:28366643). Core component of nucleosome: nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template (PubMed:19506029). Nucleosomes containing H2AB1 only wrap 130 bp of DNA, compared to 147 bp for classical nucleosomes (PubMed:19506029). In condensing spermatids, the heterodimer between H2AB1 and H2BC1/TH2B is loaded onto the nucleosomes and promotes loading of transition proteins (TNP1 and TNP2) onto the nucleosomes (PubMed:28366643). Inclusion of the H2AB1-H2BC1/TH2B dimer into chromatin opens the nucleosomes, releasing the nucleosomal DNA ends and allowing the invasion of nucleosomes by transition proteins (TNP1 and TNP2) (PubMed:28366643). Then, transition proteins drive the recruitment and processing of protamines, which are responsible for histone eviction (PubMed:28366643).|||Belongs to the histone H2A family.|||Chromosome|||Expressed since postnatal day (P) 21, peaks at P30, and gradually decreases in the testis of aging mouse (PubMed:20008104, PubMed:20188161). Coexpressed with transition proteins during late spermiogenesis (PubMed:28366643). Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Highly expressed in adult testis, mainly in spermatocytes (PubMed:20008104, PubMed:20188161, PubMed:17261847).|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Male mice are completely sterile due to defects in spermatogenesis. Chromatin in mature spermatozoa shows defects in density, due to impaired histone replacement by protamines. A significant proportion of Prm2 remains unprocessed.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers (PubMed:19506029). Incorporated into nucleosomes during late spermatogenesis (PubMed:19506029). Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847, PubMed:28366643). http://togogenome.org/gene/10090:Or52a20 ^@ http://purl.uniprot.org/uniprot/E9PV96 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hs3st2 ^@ http://purl.uniprot.org/uniprot/Q673U1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 1 family.|||Golgi apparatus membrane|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate (By similarity). Catalyzes the O-sulfation of glucosamine in GlcA2S-GlcNS (By similarity). Unlike HS3ST1/3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate (By similarity). http://togogenome.org/gene/10090:Srrt ^@ http://purl.uniprot.org/uniprot/Q99MR6 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped RNA); however interaction is probably mediated via its interaction with NCBP1/CBP80 component of the CBC complex. Involved in cell cycle progression at S phase. Does not directly confer arsenite resistance but rather modulates arsenic sensitivity. Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription.|||Belongs to the ARS2 family.|||Cytoplasm|||Death around the time of implantation. Deletion in adults leads to proliferative arrest and bone marrow hypoplasia whereas parenchymal organs composed of nonproliferating cells are unaffected.|||Interacts with CASP8AP2 and ERBB4 (By similarity). Interacts with NCBP1/CBP80 and DROSHA (PubMed:19632182). Interacts with LUZP4 (By similarity). Interacts with NCBP2/CBP20 and NCBP3 (By similarity). Interacts with MTREX (By similarity).|||Upon cell proliferation.|||Widely expressed, with a preference for proliferating cells. Highly expressed in hematopoietic tissues and reduced or absent expression in parenchymal organs like liver and kidney. In the brain, expressed in the subventricular zone by niche astrocytes, ependymal cells and neural stem cells. In this cerebral context, expressed in slowly dividing cells.|||nucleoplasm http://togogenome.org/gene/10090:Vmn1r199 ^@ http://purl.uniprot.org/uniprot/Q8R280 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Parp4 ^@ http://purl.uniprot.org/uniprot/E9PYK3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ARTD/PARP family.|||Component of the vault ribonucleoprotein particle, at least composed of MVP, PARP4 and one or more vault RNAs (vRNAs). Interacts with TEP1.|||Cytoplasm|||Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.|||No visible phenotype (PubMed:15169895). Mice are viable and fertile for up to five generations, with no apparent changes in telomerase activity or telomere length (PubMed:15169895).|||Nucleus http://togogenome.org/gene/10090:Sla ^@ http://purl.uniprot.org/uniprot/A0A0R4J247|||http://purl.uniprot.org/uniprot/Q4FJX0|||http://purl.uniprot.org/uniprot/Q60898 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. Involved in the negative regulation of positive selection and mitosis of T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins.|||Cytoplasm|||Endosome|||Expressed during thymocyte maturation. Weakly expressed in CD4(-) CD8(-) thymocytes, strongly expressed in CD4(+) CD8(+) thymocytes, while expression decreases in more mature cells.|||Homodimer. Interacts with phosphorylated CBL, SYK and LAT. Homodimerization and interaction with phosphorylated CBL occurs via its C-terminal domain (By similarity). Interacts with PDGFRB and EPHA2. Interacts with phosphorylated proteins ZAP70; CD3Z; VAV1 and LCP2 via its SH2 domain.|||Predominantly expressed in lymphoid tissues. Highly expressed in spleen, thymus and lymph nodes. Weakly expressed in lung and brain. Expressed in T-cells and at low level in B-cells.|||SLA deficient mice show a strong up-regulation of TCR and CD5 at the CD4(+) CD8(+) stage, and an enhanced positive selection in T-cells.|||The C-terminal domain is essential for the homodimerization and the interaction with CBL. While the interaction with CBL is apparently mediated via the hydrophobic region of this domain, the highly charged region is apparently required for the homodimerization (By similarity). http://togogenome.org/gene/10090:Sec62 ^@ http://purl.uniprot.org/uniprot/Q8BU14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC62 family.|||Endoplasmic reticulum membrane|||Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen.|||The ER translocon complex that consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63. Interacts with SEC61B. http://togogenome.org/gene/10090:Chst12 ^@ http://purl.uniprot.org/uniprot/Q99LL3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 2 family.|||Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin and desulfated dermatan sulfate. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Activity toward partially desulfated dermatan sulfate is however lower. Does not form 4, 6-di-O-sulfated GalNAc when chondroitin sulfate C is used as an acceptor (By similarity).|||Golgi apparatus membrane http://togogenome.org/gene/10090:Ahcy ^@ http://purl.uniprot.org/uniprot/P50247|||http://purl.uniprot.org/uniprot/Q3TF14|||http://purl.uniprot.org/uniprot/Q5M9P0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenosylhomocysteinase family.|||Binds 1 NAD(+) per subunit.|||Catalyzes the hydrolysis of S-adenosyl-L-homocysteine to form adenosine and homocysteine (PubMed:7657650). Binds copper ions (PubMed:7657650).|||Cytoplasm|||Endoplasmic reticulum|||Homotetramer. Interaction with AHCYL1 (By similarity).|||Melanosome|||Nucleus http://togogenome.org/gene/10090:Pla2g6 ^@ http://purl.uniprot.org/uniprot/P97819 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-independent phospholipase involved in phospholipid remodeling with implications in cellular membrane homeostasis, mitochondrial integrity and signal transduction. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 or sn-2 position of phospholipids (phospholipase A1 and A2 activity respectively), producing lysophospholipids that are used in deacylation-reacylation cycles (PubMed:18937505). Hydrolyzes both saturated and unsaturated long fatty acyl chains in various glycerophospholipid classes such as phosphatidylcholines, phosphatidylethanolamines and phosphatidates, with a preference for hydrolysis at sn-2 position. Can further hydrolyze lysophospholipids carrying saturated fatty acyl chains (lysophospholipase activity). Upon oxidative stress, contributes to remodeling of mitochondrial phospholipids in pancreatic beta cells, in a repair mechanism to reduce oxidized lipid content (By similarity). Preferentially hydrolyzes oxidized polyunsaturated fatty acyl chains from cardiolipins, yielding monolysocardiolipins that can be reacylated with unoxidized fatty acyls to regenerate native cardiolipin species. Hydrolyzes oxidized glycerophosphoethanolamines present in pancreatic islets, releasing oxidized polyunsaturated fatty acids such as hydroxyeicosatetraenoates (HETEs) (PubMed:24648512). Has thioesterase activity toward fatty-acyl CoA releasing CoA-SH known to facilitate fatty acid transport and beta-oxidation in mitochondria particularly in skeletal muscle (PubMed:18937505). Plays a role in regulation of membrane dynamics and homeostasis. Selectively hydrolyzes sn-2 arachidonoyl group in plasmalogen phospholipids, structural components of lipid rafts and myelin (By similarity). Regulates F-actin polymerization at the pseudopods, which is required for both speed and directionality of MCP1/CCL2-induced monocyte chemotaxis (By similarity). Targets membrane phospholipids to produce potent lipid signaling messengers. Generates lysophosphatidate (LPA, 1-acyl-glycerol-3-phosphate), which acts via G-protein receptors in various cell types. Has phospholipase A2 activity toward platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), likely playing a role in inactivation of this potent pro-inflammatory signaling lipid (By similarity). In response to glucose, amplifies calcium influx in pancreatic beta cells to promote INS secretion (PubMed:17895289).|||Cell membrane|||Cytoplasm|||Expressed in neurons of central and peripheral nervous system (PubMed:18937505, PubMed:18305254). Highly expressed in Purkinje cells in cerebellum and dorsal and ventral horn neurons in the spinal cord (PubMed:18305254). Expressed in testis (at protein level) (PubMed:18305254). Expressed in skeletal muscle (at protein level) (PubMed:18937505).|||Has two putative calmodulin binding domains, the 1-9-14 and IQ motifs. One calmodulin molecule interacts with PLA2G6 dimer, likely through 1-9-14 motif on each monomer (By similarity). Binds calmodulin in a calcium-dependent way (By similarity).|||Homodimer formed by catalytic domains tightly interacting through a large hydrophobic interface. The contact area involves 3 alpha helices, several loops and a part of the beta sheet from each monomer. Both active sites of the dimer are in close proximity adopting an open conformation that provide sufficient space for phospholipid access and favoring cooperativity in deacylation-reacylation reactions. Each monomer has 9 ankyrin repeats stacked side-by-side in an elongated structure oriented outwards from the catalytic core.|||Inhibited by calcium-activated calmodulin (By similarity). Activated by ATP (PubMed:18937505, PubMed:17895289). Inhibited by bromoenol lactone (BEL) (PubMed:18937505, PubMed:17895289).|||Knockout mice represent an appropriate model for studying the pathogenesis of neuroaxonal dystrophy in human neurodegenerative diseases (PubMed:18305254, PubMed:18937505). Mutant mice show neuroaxonal dystrophy and significant motor dysfunction from the age of 50 weeks that progressed to ataxia by 2 years (PubMed:18305254). At 55 weeks they display numerous spheroids located in the axons and synapses throughout central and peripheral nervous system, mostly prominent in the tegmentum of the medulla, the lower pons, and the dorsal horns of the spinal cord. Sciatic nerves have reduced numbers of myelinated fibers indicative of neural degeneration (PubMed:18305254). The neuroaxonal dystrophy is associated with deficient remodeling of the mitochondrial inner membrane and presynaptic membrane of axon terminals (PubMed:21813701). Mutant mice gradually lose weight and die earlier than wild-type littermates (PubMed:18305254). Mutant male mice show reduced fertility (PubMed:18305254).|||Mitochondrion|||pseudopodium http://togogenome.org/gene/10090:Vcpip1 ^@ http://purl.uniprot.org/uniprot/Q8CDG3 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds VCP and the ternary complex containing STX5A, NSFL1C and VCP.|||Cytoplasm|||Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (By similarity). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis. Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (By similarity).|||Endoplasmic reticulum|||Golgi stack|||May be due to an intron retention.|||Mice were born at nearly Mendelian ratios, although the birth rate was slightly decreased (PubMed:32649882). Mice display genomic instability and premature aging (PubMed:32649882). Cells show an accumulation of DNA-protein cross-links (DPCs) (PubMed:32649882).|||Nucleus|||Phosphorylated at Ser-1205 by ATM or ATR following induction of covalent DNA-protein cross-links (DPCs). http://togogenome.org/gene/10090:Vgll3 ^@ http://purl.uniprot.org/uniprot/E9Q1Y1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the vestigial family.|||May act as a specific coactivator for the mammalian TEFs.|||Nucleus http://togogenome.org/gene/10090:Tox ^@ http://purl.uniprot.org/uniprot/Q66JW3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Up-regulated in LCMV-specific CD8-positive T cells. Expressed at high levels in exhausted T cells during chronic infection.|||Belongs to the high motility group (HMG) box superfamily.|||Expressed in neurons of the subventricular zone (at protein level) (PubMed:25527292). Expressed in distinct subpopulations of thymocytes undergoing positive selection: double CD4-positive CD8-positive (DP) cells, CD4-positive CD8-low transitional cells and in single CD4-positive and CD8-positive cells (at protein level) (PubMed:11850626, PubMed:15078895). Expressed in ILC progenitors and mature ILC subsets: ILC1, ILC2 and ILC3 (at protein level) (PubMed:25915732). Expressed in lymphoid tissue-inducer cells and bone marrow NK cell subsets (PubMed:20818394). Abundant in thymus, liver and brain. Also detected in small intestine, spleen, stomach and testis (PubMed:11850626). Highly expressed in tumor-infiltrating CD8-positive T cells (at protein level) (PubMed:31207604).|||In the developing brain, expressed at embryonic day 9.5 dpc in neuroepithelium, displaying a rostral-high/ caudal-low and lateral-high/medial-low expression pattern. Abundant at 15.5 dpc in progenitors of the ventricular zone and differentiated neurons in the cortical plate. The lateral-medial gradient spread further in all cells of the ventricular zone of the lateral cortex by 18.5 dpc (at protein level).|||Interacts with HBO1 complex composed at least of KAT7/HBO1, ING4, MEAF6, and JADE2; this complex is involved in histone acetylation. Interacts with DNMT1, LEO1, PAF1, SAP130 and SIN3A; these interactors regulate chromatin remodeling. Interacts with an array of proteins involved in RNA processing and translation and DNA replication.|||Mutant mice lack lymph nodes. The development of Peyer's patches is compromised, detectable only in some mutants. Peyer's patches are much smaller in size less abundant when compared to wild-type littermates. T cell lymphopenia is a hallmark phenotype of TOX-deficient mice.|||Nucleus|||The HMG box is critical for TOX-dependent CD4-positive T cell lineage commitment.|||Transcriptional regulator with a major role in neural stem cell commitment and corticogenesis as well as in lymphoid cell development and lymphoid tissue organogenesis (PubMed:25527292, PubMed:20818394, PubMed:11850626, PubMed:18195075, PubMed:15078895, PubMed:25915732). Binds to GC-rich DNA sequences in the proximity of transcription start sites and may alter chromatin structure, modifying access of transcription factors to DNA (PubMed:25527292, PubMed:31207603, PubMed:31207604). During cortical development, controls the neural stem cell pool by inhibiting the switch from proliferative to differentiating progenitors. Beyond progenitor cells, promotes neurite outgrowth in newborn neurons migrating to reach the cortical plate. May activate or repress critical genes for neural stem cell fate such as SOX2, EOMES and ROBO2 (PubMed:25527292). Plays an essential role in the development of lymphoid tissue-inducer (LTi) cells, a subset necessary for the formation of secondary lymphoid organs: peripheral lymph nodes and Peyer's patches (PubMed:20818394). Acts as a developmental checkpoint and regulates thymocyte positive selection toward T cell lineage commitment (PubMed:11850626, PubMed:18195075). Required for the development of various T cell subsets, including CD4-positive helper T cells, CD8-positive cytotoxic T cells, regulatory T cells and CD1D-dependent natural killer T (NKT) cells (PubMed:18195075, PubMed:15078895). Required for the differentiation of common lymphoid progenitors (CMP) to innate lymphoid cells (ILC). May regulate the NOTCH-mediated gene program, promoting differentiation of the ILC lineage (PubMed:25915732). Required at the progenitor phase of NK cell development in the bone marrow to specify NK cell lineage commitment (PubMed:20818394). Upon chronic antigen stimulation, diverts T cell development by promoting the generation of exhaustive T cells, while suppressing effector and memory T cell programming. May regulate the expression of genes encoding inhibitory receptors such as PDCD1 and induce the exhaustion program, to prevent the overstimulation of T cells and activation-induced cell death (PubMed:31207603, PubMed:31207604).|||Transiently up-regulated during key developmental transition of immune cell subsets, likely marking a developmental checkpoint. Up-regulated during beta and positive selection of developing thymocytes, upon activation of pre-T cell receptor or T cell receptor in a calcineurin-dependent manner (PubMed:11850626, PubMed:15078895). Low expression is detected in precursor bone marrow NK cells, then is up-regulated in immature and mature bone marrow NK cells and later down-regulated in splenic mature NK cells (PubMed:20818394). http://togogenome.org/gene/10090:Sap30bp ^@ http://purl.uniprot.org/uniprot/Q02614 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HCNGP family.|||Interacts with histone deacetylase complex subunit SAP30.|||Nucleus|||Plays a role in transcriptional repression by promoting histone deacetylase activity, leading to deacetylation of histone H3 (By similarity). May be involved in the regulation of beta-2-microglobulin genes (PubMed:1459361). http://togogenome.org/gene/10090:Tgs1 ^@ http://purl.uniprot.org/uniprot/Q923W1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily. Trimethylguanosine synthase family.|||Cajal body|||Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation (By similarity).|||Cytoplasm|||May form homooligomers. Interacts with CREBBP/CBP, EED/WAIT1, EP300/P300, NCOA6/PRIP, PPARBP/PBP and SMN (By similarity).|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Defa32 ^@ http://purl.uniprot.org/uniprot/Q45VN2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Slc25a36 ^@ http://purl.uniprot.org/uniprot/Q922G0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial transporter that imports/exports pyrimidine nucleotides into and from mitochondria. Selectively transports cytosine, guanosine, inosine and uridine (deoxy)nucleoside mono-, di-, and triphosphates by antiport mechanism. Catalyzes uniport at much lower rate (By similarity). May import (deoxy)nucleoside triphosphates in exchange for intramitochondrial (deoxy)nucleoside mono- and diphosphates, thus providing precursors necessary for de novo synthesis of mitochondrial DNA and RNA while exporting products of their catabolism (By similarity). Participates in mitochondrial genome maintenance, regulation of mitochondrial membrane potential and mitochondrial respiration (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cep152 ^@ http://purl.uniprot.org/uniprot/A2AUM9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP152 family.|||Interacts (via N-terminus) with PLK4; the interaction is mutally exclusive with a PLK4:CEP192 interaction. Interacts (via C-terminus) with CENPJ (via-N-terminus). Interacts with CINP. Interacts with CDK5RAP2, WDR62, CEP63 and CEP131. CEP63, CDK5RAP2, CEP152, WDR62 are proposed to form a stepwise assembled complex at the centrosome forming a ring near parental centrioles (By similarity). Interacts with DEUP1; this interaction recruits CEP152 to the deuterosome. The interactions with CEP63 and DEUP1 are mutually exclusive (PubMed:24240477).|||Necessary for centrosome duplication; the function seems also to involve CEP63, CDK5RAP2 and WDR62 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (By similarity). Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation (By similarity). Proposed to snatch PLK4 away from PLK4:CEP92 complexes in early G1 daughter centriole and to reposition PLK4 at the outer boundary of a newly forming CEP152 ring structure (By similarity). Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (PubMed:24240477). Overexpression of cep152 can drive amplification of centrioles.|||centriole|||centrosome http://togogenome.org/gene/10090:Mboat7 ^@ http://purl.uniprot.org/uniprot/Q8CHK3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA to a lysophosphatidylinositol (1-acylglycerophosphatidylinositol or LPI) leading to the production of a phosphatidylinositol (1,2-diacyl-sn-glycero-3-phosphoinositol or PI) and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:23097495, PubMed:23472195, PubMed:32253259). Prefers arachidonoyl-CoA as the acyl donor, thus contributing to the regulation of free levels arachidonic acid in cell (PubMed:23097495, PubMed:23472195). In liver, participates in the regulation of triglyceride metabolism through the phosphatidylinositol acyl-chain remodeling regulation (PubMed:32253259).|||Belongs to the membrane-bound acyltransferase family.|||Endoplasmic reticulum membrane|||Interacts with SPTSSA; the interaction facilitates MBOAT7 location to mitochondria-associated membranes (MAMs).|||Knockout mice die within a month and show atrophy of the cerebral cortex and hippocampus. Embryos at 18.5 dpc have a forebrain smaller in size and show disordered cortical lamination and delayed neuronal migration in the cortex (PubMed:23097495, PubMed:23472195). Mice with conditional knockout in hepatocyte develop hepatic steatosis spontaneously, and hepatic fibrosis on high fat diet feeding (PubMed:32253259). http://togogenome.org/gene/10090:Ackr2 ^@ http://purl.uniprot.org/uniprot/O08707 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs.|||Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.|||Cell membrane|||Early endosome|||Expressed on apoptotic neutrophils (at protein level).|||Phosphorylated on serine residues in the C-terminal cytoplasmic tail.|||Recycling endosome|||The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties. http://togogenome.org/gene/10090:Dctn4 ^@ http://purl.uniprot.org/uniprot/Q3TQY2|||http://purl.uniprot.org/uniprot/Q8CBY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynactin subunit 4 family.|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.|||Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with ATP7B, but not ATP7A, in a copper-dependent manner (By similarity). Interacts with ANK2; this interaction is required for localization at costameres (PubMed:19109891).|||cell cortex|||centrosome|||cytoskeleton|||sarcomere|||stress fiber http://togogenome.org/gene/10090:Or55b3 ^@ http://purl.uniprot.org/uniprot/E9PWI5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rps28 ^@ http://purl.uniprot.org/uniprot/P62858|||http://purl.uniprot.org/uniprot/Q059I1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS28 family.|||Component of the 40S small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Rough endoplasmic reticulum|||cytosol|||nucleolus http://togogenome.org/gene/10090:Tmem135 ^@ http://purl.uniprot.org/uniprot/Q9CYV5 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Age-dependent pathologies, characterized by accelerated aging in the retina similar to macular degeneration of the retina (PubMed:27863209). Retina show higher sensitivity to oxidative stress (PubMed:27863209). Defects are caused by impaired balance between mitochondrial fusion and fission (PubMed:27863209).|||Belongs to the TMEM135 family.|||Involved in mitochondrial metabolism by regulating the balance between mitochondrial fusion and fission (PubMed:27863209). May act as a regulator of mitochondrial fission that promotes DNM1L-dependent fission through activation of DNM1L (PubMed:27863209). May be involved in peroxisome organization (By similarity).|||Mitochondrion membrane|||Peroxisome membrane|||Up-regulated following cold exposure and upon fasting. http://togogenome.org/gene/10090:Gfod2 ^@ http://purl.uniprot.org/uniprot/Q9CYH5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Gfo/Idh/MocA family.|||Promotes matrix assembly.|||extracellular matrix http://togogenome.org/gene/10090:Dusp7 ^@ http://purl.uniprot.org/uniprot/Q3TY83|||http://purl.uniprot.org/uniprot/Q91Z46 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Dual specificity protein phosphatase (PubMed:27783954). Shows high activity towards MAPK1/ERK2 (By similarity). Also has lower activity towards MAPK14 and MAPK8 (By similarity). In arrested oocytes, plays a role in meiotic resumption (PubMed:27783954). Promotes nuclear envelope breakdown and activation of the CDK1/Cyclin-B complex in oocytes, probably by dephosphorylating and inactivating the conventional protein kinase C (cPKC) isozyme PRKCB (PubMed:27783954). May also inactivate PRKCA and/or PRKCG (PubMed:27783954). Also important in oocytes for normal chromosome alignment on the metaphase plate and progression to anaphase, where it might regulate activity of the spindle-assembly checkpoint (SAC) complex (PubMed:27783954).|||Interacts with MAPK1/ERK2; the interaction enhances DUSP7 phosphatase activity.|||Strongly inhibited by sodium orthovanadate. http://togogenome.org/gene/10090:Cd38 ^@ http://purl.uniprot.org/uniprot/P56528|||http://purl.uniprot.org/uniprot/Q3UCS6|||http://purl.uniprot.org/uniprot/Q4FJL8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ADP-ribosyl cyclase family.|||Homodimer.|||Loss of cADPR and NAADP synthesis.|||Membrane|||Synthesizes the second messengers cyclic ADP-ribose (cADPR) and nicotinate-adenine dinucleotide phosphate (NAADP), the former a second messenger for glucose-induced insulin secretion, the latter a Ca(2+) mobilizer (PubMed:11829748). Also has cADPR hydrolase activity (By similarity). http://togogenome.org/gene/10090:Doc2b ^@ http://purl.uniprot.org/uniprot/P70169 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ C2 domain 1 is involved in binding calcium and phospholipids. According to PubMed:19033398, the C2 domain 2 may also play a role in the calcium-dependent targeting to membranes.|||Calcium sensor which positively regulates SNARE-dependent fusion of vesicles with membranes. Binds phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes.|||Cell membrane|||Cytoplasm|||Cytoplasmic granule|||Interacts with cytoplasmic dynein light chain DYNLT1. May interact with UNC13A; the interaction mediates targeting to the plasma membrane (By similarity). Probably interacts with the SNARE (soluble N-ethylmaleimide-sensitive factor attached protein receptor) complex composed of SNAP25, STX1A and VAMP2; the interaction is calcium-dependent and competitive with SYT1. Interacts with STX4; the interaction is calcium-dependent, increased by insulin and glucose, and mediates vesicle fusion with plasma membrane in pancreatic cells and adipocytes. Interacts with STXBP3; the interaction is direct, occurs at the cell membrane and regulates glucose-stimulated insulin secretion.|||Mice are viable and fertile without gross abnormalities.|||Widely expressed. Expressed in pancreatic islet cells (at protein level). http://togogenome.org/gene/10090:Gapvd1 ^@ http://purl.uniprot.org/uniprot/Q6PAR5 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts both as a GTPase-activating protein (GAP) and a guanine nucleotide exchange factor (GEF), and participates in various processes such as endocytosis, insulin receptor internalization or LC2A4/GLUT4 trafficking. Acts as a GEF for the Ras-related protein RAB31 by exchanging bound GDP for free GTP, leading to regulate LC2A4/GLUT4 trafficking. In the absence of insulin, it maintains RAB31 in an active state and promotes a futile cycle between LC2A4/GLUT4 storage vesicles and early endosomes, retaining LC2A4/GLUT4 inside the cells. Upon insulin stimulation, it is translocated to the plasma membrane, releasing LC2A4/GLUT4 from intracellular storage vesicles. Also involved in EGFR trafficking and degradation, possibly by promoting EGFR ubiquitination and subsequent degradation by the proteasome. Has GEF activity for Rab5 and GAP activity for Ras.|||Belongs to the GAPVD1 family.|||Contaminating sequence. Potential poly-A sequence.|||Endosome|||Interacts with RAB5A (By similarity). Interacts with TRIP10/CIP4.|||Membrane|||Present in adipocytes and fibroblasts (at protein level). Ubiquitously expressed. http://togogenome.org/gene/10090:Snap47 ^@ http://purl.uniprot.org/uniprot/Q8R570 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the BLOC-1 complex. Interacts with BLOC1S6 (By similarity). Forms a complex containing SNAP47, VAMP2 and STX1A.|||Belongs to the SVAP1 family.|||Endomembrane system|||Expressed as early as 10 dpc in developing brain and reaches maximal levels at 18 dpc.|||May play a role in intracellular membrane fusion.|||Ubiquitously expressed with the most abundant expression in the brain. In brain, most highly expressed in the glomerular layer of the olfactory bulb, the cortex, striatum, hippocampus, and colliculi (at protein level).|||perinuclear region http://togogenome.org/gene/10090:Eppk1 ^@ http://purl.uniprot.org/uniprot/Q8R0W0 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apicolateral cell membrane|||Basolateral cell membrane|||Belongs to the plakin or cytolinker family.|||Cell junction|||Cell projection|||Cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to stress (PubMed:16382146, PubMed:20926261, PubMed:18285451, PubMed:25232867, PubMed:25617501, PubMed:23599337). In response to mechanical stress like wound healing, is associated with the machinery for cellular motility by slowing down keratinocyte migration and proliferation and accelerating keratin bundling in proliferating keratinocytes thus contributing to tissue architecture (PubMed:16382146, PubMed:20926261). However in wound healing in corneal epithelium also positively regulates cell differentiation and proliferation and negatively regulates migration thereby controlling corneal epithelium morphogenesis and integrity (PubMed:23599337). In response to cellular stress, plays a role in keratin filament reorganization, probably by protecting keratin filaments against disruption (PubMed:18285451). During liver and pancreas injuries, plays a protective role by chaperoning disease-induced intermediate filament reorganization (PubMed:25232867, PubMed:25617501).|||High levels in skin, small intestine and salivary gland. Lower levels in lung, uterus and liver. Not detected in brain, kidney, muscle, heart or spleen. In skin, expressed in all epidermal layers but not in the dermis. In intestine, expressed exclusively in the epithelial cell layer of the villi. In liver, expressed at hepatocyte margins. Around the region of the wound, expressed in the upper half of the epidermis. Weakly expressed on the basilar side of the suprabasal layer of the epidermis at the wound's edge. Expressed strongly in the upper layer of the epidermis, especially in larger keratinocytes (PubMed:16382146). Expressed in undifferentiated primary keratinocytes (PubMed:18285451). Strongly expressed in ductal cells, and also expressed in acinar cells (PubMed:25232867). Expressed in hepatocytes and cholangiocytes (PubMed:25617501).|||Homozygous knockout mice develop normally and are healthy and fertile. Skin of homozygous knockout mice reveal no blistering and fragility. Exhibit slightly enhanced wound closure.|||Interacts with KRT5, KRT14 and KRT5/KRT14 heterotetramer; interacts preferentially with assembled filaments rather than keratin monomers (PubMed:18285451). Interacts with KRT8 and KRT18 and KRT8/KRT18 heterotetramer; interacts preferentially with assembled filaments rather than keratin monomers (PubMed:25617501). Interacts with KRT1, VIM and DES; interaction is stronger with KRT1 than with VIM or DES; interaction is dependent of higher-order structure of intermediate filament (By similarity).|||Plectin repeats are important for the binding to keratin and VIM and controls intermediate filament networks organization.|||Up-regulated upon calcium-mediated keratinocyte differentiation (PubMed:18285451). Up-regulated in hepatocytes during liver stress (PubMed:25617501).|||cytoskeleton|||hemidesmosome|||tight junction http://togogenome.org/gene/10090:Krtap13 ^@ http://purl.uniprot.org/uniprot/O88375 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Lyrm9 ^@ http://purl.uniprot.org/uniprot/Q3UN90 ^@ Similarity ^@ Belongs to the complex I LYR family. LYRM9 subfamily. http://togogenome.org/gene/10090:Slc33a1 ^@ http://purl.uniprot.org/uniprot/Q99J27 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetyl-CoA transporter that mediates active acetyl-CoA import through the endoplasmic reticulum (ER) membrane into the ER lumen where specific ER-based acetyl-CoA:lysine acetyltransferases are responsible for the acetylation of ER-based protein substrate, such as BACE1 (PubMed:24828632). Necessary for O-acetylation of gangliosides (PubMed:10570973).|||Belongs to the SLC33A transporter family.|||Endoplasmic reticulum membrane|||Expressed in all adult tissues examined including brain, heart, kidney, liver and spleen, with maximum expression in liver and kidney.|||Expression is induced in presence of ceramide.|||Highly expressed at day 7 of embryonic development. Detected at lower levels throughout the later stages of embryonic development.|||Homodimerizes. http://togogenome.org/gene/10090:Taar9 ^@ http://purl.uniprot.org/uniprot/Q5QD04 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Larp6 ^@ http://purl.uniprot.org/uniprot/Q8BN59 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in numerous tissues. Highest expression in heart and brain, intermediate in kidney, skeletal muscle and testis, lowest expression in testis (at protein level).|||Interacts (via the HTH domain) with VIM/vimentin. Interacts (via C-terminus) with non-muscle myosin MYH10. Interacts (via C-terminus) with DHX9 (By similarity).|||Nucleus|||Regulates the coordinated translation of type I collagen alpha-1 and alpha-2 mRNAs, CO1A1 and CO1A2. Stabilizes mRNAs through high-affinity binding of a stem-loop structure in their 5' UTR. This regulation requires VIM and MYH10 filaments, and the helicase DHX9 (By similarity).|||The RRM domain mediates the association with collagen mRNAs stem-loops. http://togogenome.org/gene/10090:Mex3a ^@ http://purl.uniprot.org/uniprot/G3UYU0 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Slc8b1 ^@ http://purl.uniprot.org/uniprot/Q925Q3 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.|||Cell membrane|||Conditional deletion in adult hearts causes sudden death in 87% of the mice. Hearts show substantial cardiac remodeling, including an increase in heart mass and correlative change in cardiomyocyte cross-sectional area, as well as a significant increase in cardiac fibrosis. Defects are probably due to mitochondrial calcium overload leading to increased generation of superoxide and necrotic cell death.|||Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:28445457). Strongly inhibited by zinc (By similarity).|||Isoform 1 and isoform 2 were reported to localize to the endoplasmic reticulum membrane and cell membrane, respectively (PubMed:14625281). This result is however not supported by other studies that report localization to the mitochondrial membrane (PubMed:20018762, PubMed:24067497).|||Isoform 1 was reported to not have cation exchanger activity (PubMed:12080145). However, such result is unclear.|||Mitochondrial sodium/calcium antiporter that mediates sodium-dependent calcium efflux from mitochondrion, by mediating the exchange of 3 sodium ions per 1 calcium ion (PubMed:20018762, PubMed:28445457). Plays a central role in mitochondrial calcium homeostasis by mediating mitochondrial calcium extrusion: calcium efflux is essential for mitochondrial function and cell survival, notably in cardiomyocytes (PubMed:24067497, PubMed:28445457). Regulates rates of glucose-dependent insulin secretion in pancreatic beta-cells during the first phase of insulin secretion: acts by mediating efflux of calcium from mitochondrion, thereby affecting cytoplasmic calcium responses (By similarity). Required for store-operated Ca(2+) entry (SOCE) and Ca(2+) release-activated Ca(2+) (CRAC) channel regulation: sodium transport by SLC8B1 leads to promote calcium-shuttling that modulates mitochondrial redox status, thereby regulating SOCE activity (By similarity). Involved in B-lymphocyte chemotaxis (PubMed:27328625). Able to transport Ca(2+) in exchange of either Li(+) or Na(+), explaining how Li(+) catalyzes Ca(2+) exchange (By similarity). In contrast to other members of the family its function is independent of K(+) (By similarity).|||Mitochondrion inner membrane|||Phosphorylation at Ser-258 by PKA prevents calcium overload.|||Ubiquitously expressed. Expressed in dental tissues. http://togogenome.org/gene/10090:Eif2ak1 ^@ http://purl.uniprot.org/uniprot/Q9Z2R9 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autophosphorylation; phosphorylated predominantly on serine and threonine residues, but also on tyrosine residues (PubMed:9822714, PubMed:11560503). Autophosphorylation at Thr-485 is required for kinase activation (PubMed:12767237). The active autophosphorylated form apparently is largely refractory to cellular heme fluctuations (PubMed:12767237).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.|||By phenobarbital.|||Cytoplasm|||Expressed predominantly in erythroid cells, mature reticulocytes, as well as fetal liver nucleated erythroid cells (PubMed:11689689). At much lower levels, expressed in hepatocytes and bone marrow-derived macrophages (at protein level) (PubMed:17932563).|||Highly expressed in fetal liver erythroid precursor cells at 14.5 dpc (at protein level).|||In normal conditions, the protein kinase activity is inhibited; inhibition is relieved by various stress conditions (PubMed:12767237, PubMed:14752110). Inhibited by heme: in presence of heme, forms a disulfide-linked inactive homodimer (By similarity). Heme depletion relieves inhibition and stimulates kinase activity by autophosphorylation (PubMed:12767237, PubMed:14752110). Inhibited by the heme metabolites biliverdin and bilirubin (PubMed:16893190). Induced by oxidative stress generated by arsenite treatment (PubMed:12767237). Binding of nitric oxide (NO) to the heme iron in the N-terminal heme-binding domain activates the kinase activity, while binding of carbon monoxide (CO) suppresses kinase activity (PubMed:14752110). Protein kinase activity is also activated upon binding to DELE1 in response to various stress, triggering the integrated stress response (ISR): activated by full-length DELE1 in response to iron deficiency, while it is activated by the processed form of DELE1 (S-DELE1) in response to mitochondrial stress (By similarity).|||Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:11726526, PubMed:12767237, PubMed:16893190). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:11726526, PubMed:16893190). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:11726526, PubMed:16893190). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (PubMed:16893190). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (PubMed:16893190). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (PubMed:16893190). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (PubMed:11726526, PubMed:11050009, PubMed:15931390). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (PubMed:11726526). Iron deficiency also triggers activation by full-length DELE1 (By similarity). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (By similarity).|||Mice are viable and fertile without gross morphological abnormalities but display hyperchromic anemia in animals suffering from iron deficiency (PubMed:11726526). Dramatically altered response to diet-induced iron deficiency shifting from an adaptive decrease in red blood cells (RBCs) volume and intracellular hemoglobin content to an increased production of abnormally dense red blood cells (RBCs) with decreasing red cell counts (PubMed:11726526). The decrease in RBC number is the result of increased apoptosis of erythroid precursors (PubMed:11726526). Diminished levels of phosphorylated EIF2S1 in bone marrow-derived macrophages (BMDMs) (PubMed:17932563). Impaired maturation of BMDMs and blunted inflammatory response to LPS with a reduced cytokine production. Impaired phagocytosis of senescent RBCs by macrophages, resulting in a lower phagocytosis index and lower percentage of macrophages with ingested RBC (PubMed:17932563).|||Synthesized in an inactive form that binds to the N-terminal domain of CDC37 (By similarity). Has to be associated with a multiprotein complex containing Hsp90, CDC37 and PPP5C for maturation and activation by autophosphorylation. The phosphatase PPP5C modulates this activation (By similarity). Homodimer; homodimerizes in presence of heme, forming a disulfide-linked inactive homodimer (By similarity). Interacts with DELE1; binds both to full-length DELE1 and processed form of DELE1 (S-DELE1) in response to stress, leading to activate its protein kinase activity and trigger the integrated stress response (ISR) (By similarity).|||Was reported, in hepatocytes, to be involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. Was reported that it may also regulate endoplasmic reticulum (ER) stress during acute heme-deficient conditions. However, this paper has been retracted because of improper data manipulation, reuse, and analyses. http://togogenome.org/gene/10090:Nt5c ^@ http://purl.uniprot.org/uniprot/Q9JM14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 5'(3')-deoxyribonucleotidase family.|||Cytoplasm|||Dephosphorylates the 5' and 2'(3')-phosphates of deoxyribonucleotides, with a preference for dUMP and dTMP, intermediate activity towards dGMP, and low activity towards dCMP and dAMP.|||Homodimer. http://togogenome.org/gene/10090:Kcnj4 ^@ http://purl.uniprot.org/uniprot/Q8R435|||http://purl.uniprot.org/uniprot/Q9QYK8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Membrane http://togogenome.org/gene/10090:1110025L11Rik ^@ http://purl.uniprot.org/uniprot/O09048 ^@ Similarity|||Subunit ^@ Belongs to the KRTAP type 6 family.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Cldn16 ^@ http://purl.uniprot.org/uniprot/Q14BW2|||http://purl.uniprot.org/uniprot/Q925N4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Involved in paracellular magnesium reabsorption. Required for a selective paracellular conductance. May form, alone or in partnership with other constituents, an intercellular pore permitting paracellular passage of magnesium and calcium ions down their electrochemical gradients. Alternatively, it could be a sensor of magnesium concentration that could alter paracellular permeability mediated by other factors (By similarity).|||tight junction http://togogenome.org/gene/10090:Scgb2b3 ^@ http://purl.uniprot.org/uniprot/D2XZ38 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Palld ^@ http://purl.uniprot.org/uniprot/Q9ET54 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the myotilin/palladin family.|||Cytoskeletal protein required for organization of normal actin cytoskeleton. Roles in establishing cell morphology, motility, cell adhesion and cell-extracellular matrix interactions in a variety of cell types. May function as a scaffolding molecule with the potential to influence both actin polymerization and the assembly of existing actin filaments into higher-order arrays. Binds to proteins that bind to either monomeric or filamentous actin. Localizes at sites where active actin remodeling takes place, such as lamellipodia and membrane ruffles. Different isoforms may have functional differences. Involved in the control of morphological and cytoskeletal changes associated with dendritic cell maturation. Involved in targeting ACTN to specific subcellular locations. May be required for the initiation of neural tube closure.|||Death around 15.5 dpc due to severe neural tube closure defects and herniation of liver and intestine. Palld-deficient mouse embryonic fibroblasts display disorganized actin cytoskeleton, decreased polymerized filament actin, and decreased cell adhesion and compromised cell spreading on various extracellular matrix. Mice embryos lacking Palld exhibit defects in erythropoiesis.|||Detected in both muscle and non-muscle tissues and cells (at protein level). Isoform 3 is widely expressed, isoform 4 is particularly abundant in tissues rich in smooth muscle and in the cardiac muscle and isoform 1 is detected in heart.|||Interacts with EPS8 (PubMed:16868024). Interacts with LASP1 (PubMed:16492705). Interacts with VASP (PubMed:14983521). Interacts with ACTN (By similarity). Interacts with SORBS2 (By similarity). Interacts with PFN1 (By similarity). Interacts with LPP (By similarity). Interacts with SPIN90 (By similarity). Interacts with SRC (By similarity). Interacts with EZR (By similarity). Interacts with RAI14 (By similarity).|||Phosphorylated predominantly on serines and, to a lesser extent, on tyrosines. Phosphorylation at Ser-1143 by PKB/AKT1 modulates cytoskeletal organization and cell motility (By similarity).|||Ubiquitously detected in embryonic tissues, and down-regulated in certain adult tissues (at protein level). Isoform 3 is widely expressed in embryonic tissues (at protein level). In adults is detected in spleen and gut, and is almost undetectable in heart, skeletal muscle, liver, and kidney (at protein level). Isoform 4 is widely expressed in neonatal tissues (brain, heart, lung, stomach, intestine, kidney, bone and skin) (at protein level). Late in development expression is restricted to cardiac muscle and to organs rich in smooth muscle (at protein level). Isoform 1 is detected in neonatal striated muscle and bone, and remains highly expressed in adult skeletal and cardiac muscle (at protein level). Adult brain express an isoform of 80-85 kDa. At 8.5 dpc is mainly expressed the rostral and caudal part of neural plate. No expression is detected in somite. At 9.5 dpc and 10.5 dpc is ubiquitously detected.|||Z line|||axon|||cytoskeleton|||focal adhesion|||growth cone|||lamellipodium|||podosome|||ruffle http://togogenome.org/gene/10090:Celf5 ^@ http://purl.uniprot.org/uniprot/D3Z4T1|||http://purl.uniprot.org/uniprot/D3Z580 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CELF/BRUNOL family.|||Nucleus http://togogenome.org/gene/10090:Chmp6 ^@ http://purl.uniprot.org/uniprot/B1AZ39|||http://purl.uniprot.org/uniprot/P0C0A3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||Endomembrane system|||Endosome membrane|||ISGylated in a CHMP5-dependent manner. Isgylation weakens its interaction with VPS4A (By similarity).|||Late endosome membrane|||Membrane|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes (By similarity).|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with CHMP4A, CHMP4B and CHMP4C. Interacts with SNF8, VPS25 and VPS36 (By similarity).|||The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components (By similarity). http://togogenome.org/gene/10090:Hdac11 ^@ http://purl.uniprot.org/uniprot/Q543U1|||http://purl.uniprot.org/uniprot/Q91WA3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone deacetylase family.|||Interacts with HDAC6.|||Its activity is inhibited by trapoxin, a known histone deacetylase inhibitor.|||Nucleus|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes (By similarity). http://togogenome.org/gene/10090:Stac3 ^@ http://purl.uniprot.org/uniprot/Q8BZ71 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Complete perinatal lethality, due to paralysis and inability to breathe (PubMed:23626854, PubMed:23818578). Embryos have a curved body with abnormal curvature of the vertebral spine and drooping forelimbs (PubMed:23626854, PubMed:23818578). They display multiple skeletal abnormalities involving ribs, sternum and costal cartilage, and strongly reduced formation of bone ridges at major muscle attachment sites (PubMed:23818578). They weigh about 15% less than wild-type at 18.5 dpc (PubMed:23626854). They do not move or respond to touch, but have a beating heart when dissected out of the uterus (PubMed:23626854). Their myofibers have altered morphology with centrally located nuclei, unlike wild-type, where the nuclei are located in the periphery of the myofibers (PubMed:23626854, PubMed:23818578). Sarcomeres have streaming Z-lines (PubMed:23626854). The diaphragm does not contract in response to membrane depolarization or electric stimulation (PubMed:23818578). Myotubes from mutant mice lack voltage-induced calcium release from the sarcoplasmic reticulum (PubMed:23818578).|||Cytoplasm|||Dected in skeletal muscle, including soleus, extensor digitorum longus, tibialis anterior, quadriceps and gastrocnemius. Detected in tongue.|||Detected in somites and limb buds at 9.5 and 13 dpc, in embryonic limb muscle and tongue (PubMed:23626854, PubMed:23818578). Detected in tongue and diaphragm at 14.5 dpc (PubMed:23818578).|||Interacts (via SH3 domains) with the calcium channels CACNA1S and CACNA1C (PubMed:28112192, PubMed:29467163, PubMed:29363593). Component of a calcium channel complex with CACNA1S and CACNB1 (PubMed:28112192). Component of a calcium channel complex with CACNA1C and CACNB1 (PubMed:28112192).|||Required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization (PubMed:23818578, PubMed:27621462, PubMed:29467163). Required for normal Ca(2+) release from the sarcplasmic reticulum, which ultimately leads to muscle contraction (PubMed:23818578). Probably functions via its effects on muscle calcium channels. Increases CACNA1S channel activity, in addition to its role in enhancing the expression of CACNA1S at the cell membrane (PubMed:27621462). Has a redundant role in promoting the expression of the calcium channel CACNA1S at the cell membrane (PubMed:25548159, PubMed:27621462, PubMed:29467163). Slows down the inactivation rate of the calcium channel CACNA1C (PubMed:25548159, PubMed:29363593).|||T-tubule|||sarcolemma http://togogenome.org/gene/10090:Tmem167 ^@ http://purl.uniprot.org/uniprot/Q9CR64 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the KISH family.|||Golgi apparatus membrane|||Involved in the early part of the secretory pathway. http://togogenome.org/gene/10090:Tnfsf15 ^@ http://purl.uniprot.org/uniprot/A0A0U5J7F3|||http://purl.uniprot.org/uniprot/B2RR33|||http://purl.uniprot.org/uniprot/Q5UBV8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Homotrimer.|||Membrane|||Receptor for TNFRSF25 and TNFRSF6B. Mediates activation of NF-kappa-B. Inhibits vascular endothelial growth and angiogenesis (in vitro). Promotes activation of caspases and apoptosis (By similarity). Promotes splenocyte alloactivation.|||Up-regulated by TNF-alpha. http://togogenome.org/gene/10090:Ndufv3 ^@ http://purl.uniprot.org/uniprot/Q3U422|||http://purl.uniprot.org/uniprot/Q8BK30 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. May be the terminally assembled subunit of Complex I.|||Belongs to the complex I NDUFV3 subunit family.|||Complex I is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Rplp2 ^@ http://purl.uniprot.org/uniprot/P99027 ^@ Function|||Similarity|||Subunit ^@ Belongs to the eukaryotic ribosomal protein P1/P2 family.|||Heterodimer with RPLP1 at the lateral ribosomal stalk of the large ribosomal subunit.|||Plays an important role in the elongation step of protein synthesis. http://togogenome.org/gene/10090:Cblif ^@ http://purl.uniprot.org/uniprot/P52787 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic cobalamin transport proteins family.|||Gastric mucosa.|||Interacts with CUBN (via CUB domains).|||Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the CBLIF-cobalamin complex is internalized via receptor-mediated endocytosis (By similarity).|||Secreted http://togogenome.org/gene/10090:Degs1l ^@ http://purl.uniprot.org/uniprot/Q3TS87 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Slc39a14 ^@ http://purl.uniprot.org/uniprot/Q75N73 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Early endosome membrane|||Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15863613, PubMed:16950869, PubMed:18270315, PubMed:19179618, PubMed:21653899, PubMed:28673968). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (PubMed:18270315). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (PubMed:18270315). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (PubMed:25428902). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (PubMed:21445361). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (PubMed:28673968). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (By similarity). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (PubMed:28536273). Also functions in the extracellular uptake of free iron (PubMed:16950869, PubMed:19179618, PubMed:21653899, PubMed:23110240, PubMed:26028554). May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages (By similarity).|||Homotrimer.|||Homozygous knockout mice exhibit growth retardation and dwarfism, visible even in neonates (PubMed:21445361). They exhibit moderate osteoporotic phenotypes associated with decreased bone volume and trabecular number, and increased trabecular separation (PubMed:21445361). The length of the long bones is also significantly reduced (PubMed:21445361). The decrease in bone mass is associated with increased bone resorption (PubMed:29632817). The metabolism of these mice is also affected and they constitute a model of metabolic endotoxemia with high body fat, hypoglycemia and hyperinsulinemia (PubMed:23110240, PubMed:27703010). The knockout of the gene also results in less effective blood manganese elimination and accumulation in the brain where it alters motor functions (PubMed:28536273). Knockout mice also display increased iron absorption and decreased lipopolysaccharide/LPS-induced IL-6 production (PubMed:23110240, PubMed:26028554). The permeability of the intestinal barrier is also compromised (PubMed:25428902). Conditional intestinal-specific knockout of the gene results in increased manganese levels in brain and liver while the liver-specific knockout reduces manganese levels only in liver (PubMed:31028174).|||In the KS483 cell model for osteoblast differentiation, expression levels peaks during the mineralization phase (days 18-21 of differentiation).|||Inhibited by cyanide and therefore dependent of an energy source (PubMed:18270315). Inhibited by DIDS/4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor hydrogencarbonate-dependent transporters (PubMed:18270315).|||Late endosome membrane|||Lysosome membrane|||More strongly expressed in brain.|||More strongly expressed in liver, kidney and duodenum.|||N-glycosylated (PubMed:18270315, PubMed:21445361). N-glycosylation at Asn-100 is required for iron-regulated extraction of the transporter from membranes and subsequent proteasomal degradation (By similarity).|||Probable cloning artifact.|||Ubiquitinated. Ubiquitination occurs upon iron depletion. The ubiquitinated form undergoes proteasomal degradation.|||Up-regulated during the lipopolysaccharide/LPS-induced inflammatory response (at protein level) (PubMed:16950869). Up-regulated by IL6 (PubMed:15863613, PubMed:16950869, PubMed:17065364). Up-regulated by interleukin-1/IL1 via nitric oxide (PubMed:19179618). Up-regulated upon endoplasmic reticulum stress induced by tunicamycin or high-fat diet (at protein level) (PubMed:28673968). Up-regulated into hepatocytes upon glucose uptake (at protein level) (PubMed:27703010). Up-regulated by iron in retina (at protein level) (PubMed:28057442).|||Widely expressed (PubMed:18270315). Highly and transiently expressed during the early stage of adipocyte differentiation. Strongly expressed in liver, preadipocyte, duodenum and jejunum, moderately in brain, heart, skeletal muscle, spleen, pancreas, kidney and white adipose cells. Expression is almost undetectable in lung, testis and brown adipose cells (PubMed:15794747, PubMed:15863613, PubMed:16950869, PubMed:17065364, PubMed:25428902). Expressed by chondrocytes and pituitary cells (PubMed:21445361). http://togogenome.org/gene/10090:Lhfpl5 ^@ http://purl.uniprot.org/uniprot/B2RWL4|||http://purl.uniprot.org/uniprot/Q4KL25 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LHFP family.|||Brain, inner ear hair cells and vestibular neuroepithelia of the inner ear (PubMed:16459341, PubMed:23217710, PubMed:15905332). In inner ear, expressed in stereocilia in a punctate pattern and at the tip-link region (at protein level) (PubMed:16459341, PubMed:23217710, PubMed:15905332). Strongly expressed in brain (PubMed:26964900). Weakly expressed in heart, testis and intestine (PubMed:26964900).|||Cell membrane|||Defects in Lhfpl5 are the cause of the hurry-scurry (hscy) phenotype which is characterized by rapid circling behavior, frequent shaking of head from side to side, deafness and vestibular dysfunction.|||Expressed in inner ear hair cells at 16.5 dpc. Expressed postnatally in inner and outer hair cells of the cochlear, as well as in vestibular hair cells. At the cochlear apex, levels are low at P1 and increased thereafter. After P7, hardly detectable at the protein level, while mRNA levels remains high in adult hair cells.|||Found in a complex with TMIE and PCDH15 (PubMed:25467981). Interacts with PCDH15; this interaction is required for efficient localization to hair bundles (PubMed:23217710). Interacts with TOMT (PubMed:28504928).|||In the inner ear, may be a component of the hair cell's mechanotransduction machinery that functionally couples PCDH15 to the transduction channel. Regulates transducer channel conductance and is required for fast channel adaptation.|||Membrane http://togogenome.org/gene/10090:Slc17a5 ^@ http://purl.uniprot.org/uniprot/Q8BN82 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.|||Expressed in hippocampal neurons (at protein level).|||Lysosome membrane|||Multifunctional anion transporter that operates via two distinct transport mechanisms, namely proton-coupled anion cotransport and membrane potential-dependent anion transport (PubMed:18695252) (By similarity). Electroneutral proton-coupled acidic monosaccharide symporter, with a sugar to proton stoichiometry of 1:1. Exports glucuronic acid and free sialic acid derived from sialoglycoconjugate degradation out of lysosomes, driven by outwardly directed lysosomal pH gradient. May regulate lysosome function and metabolism of sialylated conjugates that impact oligodendrocyte lineage differentiation and myelinogenesis in the central nervous system (By similarity) (PubMed:20007460). Electrogenic proton-coupled nitrate symporter that transports nitrate ions across the basolateral membrane of salivary gland acinar cells, with nitrate to proton stoichiometry of 2:1. May contribute to nitrate clearance from serum by salivary glands, where it is further concentrated and secreted in the saliva (By similarity). Uses membrane potential to drive the uptake of acidic amino acids and peptides into synaptic vesicles. Responsible for synaptic vesicular storage of L-aspartate and L-glutamate in pinealocytes as well as vesicular uptake of N-acetyl-L-aspartyl-L-glutamate neuropeptide, relevant to aspartegic-associated glutamatergic neurotransmission and activation of metabotropic receptors that inhibit subsequent transmitter release (PubMed:18695252, PubMed:23889254).|||Mutant mice have smaller size, develop severe tremor and uncoordinated gait associated with marked central nervous system hypomyelination, and die prematurely during the third postnatal week.|||Receptor for CM101, a polysaccharide produced by group B Streptococcus with antipathoangiogenic properties.|||synaptic vesicle membrane http://togogenome.org/gene/10090:H2ac6 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Cetn2 ^@ http://purl.uniprot.org/uniprot/Q9R1K9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.|||Belongs to the centrin family.|||Binds two moles of calcium per mole of protein.|||Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with Rad23b appears to stabilize Xpc. In vitro, stimulates DNA binding of the Xpc:Rad23b dimer (By similarity).|||Monomer. Homooligomer. Interacts with CCP110, SFI1. Component of the XPC complex composed of XPC, RAD23B and CETN2 (By similarity). Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153 (By similarity).|||Nucleus|||Nucleus envelope|||Plays a fundamental role in microtubule organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CCP110 (By similarity).|||The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, Xpa, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair (By similarity).|||Ubiquitously expressed in all adult tissues tested, with strongest expression in brain, spleen, kidney, small intestine and ovary. Also expressed in the NIH 3T3 fibroblast cell line and peripheral blood lymphocytes.|||centriole|||centrosome|||nuclear pore complex http://togogenome.org/gene/10090:Mcl1 ^@ http://purl.uniprot.org/uniprot/P97287 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Bcl-2 family.|||Cleaved by CASP3 during apoptosis, yielding a pro-apoptotic C-terminal fragment.|||Cytoplasm|||Interacts with HIF3A isoform 2 (via C-terminus domain) (PubMed:21546903). Interacts with BAD, BOK, BIK, BAX, BAK1, and TPT1. Interacts with BBC3, BMF and PMAIP1 (PubMed:15550399, PubMed:18589438). Interacts with BOP. Interacts with BCL2L11; this interaction may sequester BCL2L11 and prevent its pro-apoptotic activity (PubMed:16543145, PubMed:27013495, PubMed:15550399). Interacts with GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and MCL1 is impaired in the absence of GIMAP5 (PubMed:21502331).|||Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 2 has antiapoptotic activity.|||Membrane|||Mitochondrion|||Phosphorylated on Ser-140, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-140 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity. Treatment with taxol or okadaic acid induces phosphorylation on additional sites.|||Rapidly degraded in the absence of phosphorylation in the PEST region.|||This isoform is more stable than isoform 1 in cells undergoing apoptosis.|||Ubiquitinated. Ubiquitination is induced by phosphorylation at Ser-140 (By similarity). Deubiquitinated by USP20; leading to increased stability.|||Up-regulated by IL3 and CSF2. Up-regulated in murine embryonal carcinoma cells in response to retinoic acid treatment. Levels reach a maximum after 4 hours, are decreased after 8 hours and are back to maximum after 12 hours. Levels are decreased after 24 hours and back to basal levels after 48 hours. Expression remains constant in retinoic acid-treated embryonic stem cells.|||nucleoplasm http://togogenome.org/gene/10090:Tfdp2 ^@ http://purl.uniprot.org/uniprot/E9PWL5|||http://purl.uniprot.org/uniprot/F6QG91|||http://purl.uniprot.org/uniprot/J3QK26|||http://purl.uniprot.org/uniprot/Q3TY79|||http://purl.uniprot.org/uniprot/Q56A02|||http://purl.uniprot.org/uniprot/Q8BHD2|||http://purl.uniprot.org/uniprot/Q8C537|||http://purl.uniprot.org/uniprot/Q8C8M7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the E2F/DP family.|||Nucleus http://togogenome.org/gene/10090:Grxcr1 ^@ http://purl.uniprot.org/uniprot/Q50H32 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GRXCR1 family.|||Defects in Grxcr1 are the cause of the pirouette (pi) phenotype which is characterized by vestibular defects and profound deafness with affected mice displaying abnormally thin and slightly shortened sterocilia.|||In the inner ear, expressed predominantly in sensory hair cells and their stereocilia bundles with higher levels in outer hair cells (OHC) at P1 and in inner hair cells (IHC) at P5. At P1, expression is prominent in each row of stereocilia within bundles including immature shorter stereocilia. Expression is also observed in apical microvilli of sensory cells at P1 and in kinocilia at P1 and P5. In the adult, expression is localized throughout the length of the stereocilia of both OHC and IHC (at protein level).|||May play a role in actin filament architecture in developing stereocilia of sensory cells.|||kinocilium|||microvillus|||stereocilium http://togogenome.org/gene/10090:Dppa3 ^@ http://purl.uniprot.org/uniprot/Q8QZY3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Detected at 3.5 dpc (at protein level). Activated during the process of germ cell specification at 7 dpc.25, specifically in the founder population of lineage-restricted primordial germ cells (PGCs). Thereafter, expressed in the germ line until about 15.5 dpc in male and 13.5 dpc in female gonads. Expressed during blastocyst, morula and 4-cell embryo stages.|||Expressed in the immature oocytes and in newborn ovaries. Subsequently detected in maturing oocytes and in preimplantation embryos. Expressed in pluripotent embryonic but not in differentiated somatic cells. Expressed in blastocysts, epiblasts, primordial germ cells, embryonic gonads and primitive spermatogonia. No expression is detected in adult testes.|||Mediates binding to H3K9me2 via N-terminal region, while ability to exclude TET3 from the maternal pronucleus requires the C-terminal part.|||Nucleus|||Null mutation result in apparently normal offspring. No effect on early gonadal PGCs or gross abnormalities in the development of gametes. However, females display severely reduced fertility despite ovulation of normal numbers of oocytes. Null mutation resulted in preimplantation development failure. Embryos rarely reached the blastocyst stage.|||Primordial germ cell (PGCs)-specific protein involved in epigenetic chromatin reprogramming in the zygote following fertilization. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in protection of DNA methylation in the maternal pronucleus by preventing conversion of 5mC to 5hmC: specifically recognizes and binds histone H3 dimethylated at 'Lys-9' (H3K9me2) on maternal genome, and protects maternal genome from TET3-mediated conversion to 5hmC and subsequent DNA demethylation. Does not bind paternal chromatin, which is mainly packed into protamine and does not contain much H3K9me2 mark. Also protects imprinted loci that are marked with H3K9me2 in mature sperm from DNA demethylation in early embryogenesis. May be important for the totipotent/pluripotent states continuing through preimplantation development. Also involved in chromatin condensation in oocytogenesis. http://togogenome.org/gene/10090:Phf5a ^@ http://purl.uniprot.org/uniprot/P83870 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PHF5 family.|||Expressed in primary spermatocytes (at protein level) (PubMed:18758164). Ubiquitously expressed in pre- and postnatal tissues (PubMed:12054543). Highly expressed in pluripotent embryonic stem cells (ESCs) (at protein level) and induced pluripotent stem cells (iPSCs) (PubMed:27749823).|||Expression levels are down-regulated following differentiation in embryonic stem cells (ESCs) and in differentiated mouse embryonic fibroblasts (MEFs).|||Interacts (via N-terminus) with U2AF1 and SRSF5; acts to bridge the two. Interacts (via C-terminus) with EP400 and DDX1; acts to bridge the two (PubMed:18758164). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42. Within the SF3B complex interacts directly with SF3B1 and SF3B3. The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2. SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Component of the minor spliceosome, also called U12-type spliceosome, which splices U12-type introns. Within this complex, interacts with CRIPT (By similarity). Interacts with the PAF1 complex (PAF1C) composed of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. Within the PAF1C interacts directly with CDC73 and SKIC8. Interacts with RNA polymerase II (PubMed:27749823).|||Involved with the PAF1 complex (PAF1C) in transcriptional elongation by RNA polymerase II, and in regulation of development and maintenance of embryonic stem cell (ESC) pluripotency. Required for maintenance of ESCs self-renewal and cellular reprogramming of stem cells. Maintains pluripotency by recruiting and stabilizing PAF1C on pluripotency genes loci, and by regulating the expression of the pluripotency genes. Regulates the deposition of elongation-associated histone modifications, including dimethylated histone H3 'Lys-79' (H3K79me2) and trimethylated histone H3 'Lys-36' (H3K36me3), on PAF1C targets, self-renewal and pluripotency genes. Regulates RNA polymerase II promoter-proximal pause release of the PAF1C targets and self-renewal genes, and the levels of elongating ('Ser-2' phosphorylated) RNA polymerase II in their gene bodies. Regulates muscle specification in adult stem cells by stabilizing PAF1C in chromatin to promote myogenic differentiation (PubMed:27749823). Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (By similarity). Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha (By similarity). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Tomm20l ^@ http://purl.uniprot.org/uniprot/Q9D4V6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Tom20 family.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Psd3 ^@ http://purl.uniprot.org/uniprot/Q2PFD7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed only in spinal cord at 13 dpc. At 18 dpc and P0, appears weakly in forebrain. Expression in brain increases after birth and peaks at P10.|||Guanine nucleotide exchange factor for ARF6.|||Postsynaptic density|||Ubiquitously expressed, with highest levels in liver. Present in brain, with highest levels in olfactory bulb, cortex, hippocampal pyramidal cell layer and cerebellar granule cell layer (at protein level).|||ruffle membrane http://togogenome.org/gene/10090:Scaf4 ^@ http://purl.uniprot.org/uniprot/Q7TSH6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Anti-terminator protein required to prevent early mRNA termination during transcription. Together with SCAF8, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins. Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation. Independently of SCAF8, also acts as a suppressor of transcriptional readthrough.|||Interacts with POLR2A; via C-terminal heptapeptide repeat domain (CTD) phosphorylated at 'Ser-2' and 'Ser-5'.|||Nucleus http://togogenome.org/gene/10090:Degs1 ^@ http://purl.uniprot.org/uniprot/O09005 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.|||Detected in testis. Detected in pachytene spermatocytes and round spermatids. Expressed in retina and retinal pigment epithelium by Mueller cells (at protein level) (PubMed:23143414).|||Endoplasmic reticulum membrane|||Has sphingolipid-delta-4-desaturase activity. Converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine). Catalyzes the equilibrium isomerization of retinols (By similarity).|||Interacts with RLBP1; the interaction increases synthesis of chromophore-precursors by DEGS1.|||Mitochondrion membrane|||Myristoylation can target the enzyme to the mitochondria leading to an increase in ceramide levels. http://togogenome.org/gene/10090:Hoxd4 ^@ http://purl.uniprot.org/uniprot/P10628 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Antp homeobox family. Deformed subfamily.|||Forms a DNA-binding heterodimer with transcription factor PBX1.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Ces2a ^@ http://purl.uniprot.org/uniprot/Q8QZR3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Carboxylesterases that catalyzes the hydrolysis of pyrethroids pesticides. Hydrolyzes permethrin faster than cypermethrin. Hydrolyzes retinyl esters (By similarity).|||Microsome http://togogenome.org/gene/10090:Eloc ^@ http://purl.uniprot.org/uniprot/A0A087WNT1|||http://purl.uniprot.org/uniprot/P83940 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKP1 family.|||Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. This includes the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. As part of a multisubunit ubiquitin ligase complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (By similarity). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (PubMed:33590678).|||Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit (By similarity). The elongin BC complex interacts with EPOP; leading to recruit the elongin BC complex to Polycomb group (PcG) target genes, thereby restricting excessive activity of the PRC2/EED-EZH2 complex (PubMed:27863225, PubMed:27863226). Part of E3 ubiquitin ligase complexes with CUL5 or CUL2, RBX1 and a substrate adapter protein that can be either ASB2, KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B, FEM1C, LRR1, SOCS1, SOCS5, ELOA, VHL or WSB1 (PubMed:10051596, PubMed:11384984, PubMed:9869640, PubMed:33590678). The elongin BC complex is part of a complex with VHL and hydroxylated HIF1A. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC. Interacts with VHL. Interacts with TMF1. Interacts with SPSB1. Interacts with SPSB1. Interacts with KLHDC10; which may be an E3 ubiquitin ligase complex substrate recognition component. Interacts with NOS2 in the presence of SPSB1 or SPSB2 or SPSB4 (By similarity). As part of the Elongin BC E3 ubiquitin ligase complex; interacts with NRBP1 (By similarity). Component of the ECS(PCMTD1) complex with the substrate recognition subunit PCMTD1. Interacts with PCMTD1 (via the BC-box); the interaction is direct and stabilizes PCMTD1 (By similarity).|||Nucleus|||SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex) (By similarity). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells (PubMed:27863225, PubMed:27863226).|||Ubiquitinated by the DCX(AMBRA1) complex, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Mrpl22 ^@ http://purl.uniprot.org/uniprot/Q8BU88 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL22 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Trim30a ^@ http://purl.uniprot.org/uniprot/P15533 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By the TLR ligands lipopolysaccharide, CpG dinucleotide and polyinosinic-polycytidylic acid.|||Cytoplasm|||Highly expressed in spleen and lymph nodes (at protein level).|||Homomultimer. Interacts with NR2C2/TAK1, TAB2 and TAB3. Does not interact with NLRP3, NLRC4 or TAB1.|||Nucleus|||Trans-acting factor that regulates gene expression of interleukin 2 receptor alpha chain. May affect IL2R-alpha expression through cis-acting negative regulatory elements or through competition with proteins that bind to enhancer or activator sequences. Negatively regulates Toll-like receptor (TLR)-mediated activation of NFKB by promoting degradation of TAB2 and TAB3 and preventing TRAF6 autoubiquitination. Negatively regulates production of reactive oxygen species (ROS) which inhibits activation of the NLRP3 inflammasome complex. This, in turn, regulates activation of CASP1 and subsequent cleavage of IL1B and IL18. No activity detected against a range of retroviruses including a number of lentiviruses, gammaretroviruses and betaretroviruses. http://togogenome.org/gene/10090:Psma3 ^@ http://purl.uniprot.org/uniprot/E0CX62|||http://purl.uniprot.org/uniprot/O70435|||http://purl.uniprot.org/uniprot/Q3TEL1|||http://purl.uniprot.org/uniprot/Q58EV4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Binds to the C-terminus of CDKN1A and thereby mediates its degradation. Negatively regulates the membrane trafficking of the cell-surface thromboxane A2 receptor (TBXA2R) isoform 2.|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Interacts with AURKB. Interacts with CDKN1A. Interacts with MDM2 and RB1. Interacts with the C-terminus of TBXA2R isoform 2. Interacts with DNAJB2. http://togogenome.org/gene/10090:Sugct ^@ http://purl.uniprot.org/uniprot/Q3TV98|||http://purl.uniprot.org/uniprot/Q7TNE1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CoA-transferase III family.|||Catalyzes the succinyl-CoA-dependent conversion of glutarate to glutaryl-CoA. Can use different dicarboxylic acids as CoA acceptors, the preferred ones are glutarate, succinate, adipate, and 3-hydroxymethylglutarate (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Or2g1 ^@ http://purl.uniprot.org/uniprot/Q8VFQ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chmp1b ^@ http://purl.uniprot.org/uniprot/Q99LU0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||Endosome|||Late endosome membrane|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B and SPAST to the midbody of dividing cells (By similarity).|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with CHMP1A. Interacts with VTA1; the interaction probably involves the open conformation of CHMP1B. Interacts with CHMP2A. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with SPAST (via MIT domain); the interaction is direct. Interacts with IST1. Interacts with MITD1. Interacts with STAMBP (By similarity).|||cytosol http://togogenome.org/gene/10090:Aanat ^@ http://purl.uniprot.org/uniprot/O88816 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the acetyltransferase family. AANAT subfamily.|||Controls the night/day rhythm of melatonin production in the pineal gland. Catalyzes the N-acetylation of serotonin into N-acetylserotonin, the penultimate step in the synthesis of melatonin.|||Cytoplasm|||Exhibits night/day variations with a drastically increased expression at night in the pineal gland.|||Highly expressed in pineal gland at night. Expression in the retina has not been confirmed. Extrapineal expression could be strain-specific.|||Monomer (By similarity). Interacts with several 14-3-3 proteins, including YWHAB, YWHAE, YWHAG and YWHAZ, preferentially when phosphorylated at Thr-29 (By similarity). Phosphorylation on Ser-203 also allows binding to YWHAZ, but with lower affinity (By similarity). The interaction with YWHAZ considerably increases affinity for arylalkylamines and acetyl-CoA and protects the enzyme from dephosphorylation and proteasomal degradation. It may also prevent thiol-dependent inactivation (By similarity).|||Pineal melatonin synthesis is severely compromised in most inbred strains of mice. In C57BL/6, a polymorphism activates a cryptic splice site causing the production of an alternative form containing a premature stop codon. The predicted resulting protein would lack the putative catalytic and acetyl-CoA binding domains and therefore would be inactive.|||cAMP-dependent phosphorylation on both N-terminal Thr-29 and C-terminal Ser-203 regulates AANAT activity by promoting interaction with 14-3-3 proteins. http://togogenome.org/gene/10090:Spg11 ^@ http://purl.uniprot.org/uniprot/Q3UHA3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in all brain areas analyzed from embryonic (18 dpc) and adult mice.|||Interacts with AP5Z1, AP5B1, AP5S1 and ZFYVE26.|||May play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport.|||Nucleus|||Synapse|||Ubiquitously expressed at low level. Expressed in embryonic and adult cortical projection neurons.|||axon|||cytosol|||dendrite http://togogenome.org/gene/10090:Fbxo5 ^@ http://purl.uniprot.org/uniprot/Q7TSG3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Death at the preimplantation stage. Embryos display normal cell proliferation but mitotic progression is severely defective during embryonic cleavage with multipolar spindles and misaligned chromosomes frequently observed.|||Detected at the germinal vesicle (GV) stage. During maturation, decreases to barely detectable levels in meiosis I- and meiosis II-stage oocytes.|||Expressed in oocytes and granulosa cells (PubMed:15526037, PubMed:17190794). Expressed in proliferating cells compartments in hair follicle and skin epidermis, spermatogonia, and intestinal crypts (PubMed:17875940).|||Nucleus|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with BTRC; mediates proteolysis by the SCF ubiquitin ligase complex leading to activation of APC in late mitosis and subsequent mitotic progression. Interacts with FZR1/CDH1 and the N-terminal substrate-binding domain of CDC20; prevents APC activation. Also interacts with EVI5 which blocks its phosphorylation by PLK1 and prevents its subsequent binding to BTRC and degradation. Interacts simultaneously with anaphase promoting complex (APC), through at least ANAPC2, CDC23, CDC27, the APC substrate GMNN and the APC activator FZR1. Interacts with UBE2S; interferes with the activity of UBE2S mainly by disrupting the dynamic electrostatic association between the C-terminal tail of UBE2S and ANAPC2 (By similarity). Interacts with RPS6KA2; cooperates to induce the metaphase arrest of early blastomeres; increases and stabilizes interaction of FBXO5 with CDC20 (PubMed:15526037).|||Phosphorylation by CDK2 and subsequently by PLK1 triggers degradation during early mitosis through ubiquitin-mediated proteolysis by the SCF ubiquitin ligase complex containing the F-box protein BTRC. This degradation is necessary for the activation of APC in late mitosis and subsequent mitotic progression (By similarity). Phosphorylated by RPS6KA2; increases and stabilizes interaction with CDC20 (PubMed:15526037).|||Regulator of APC activity during mitotic and meiotic cell cycle (PubMed:17190794, PubMed:15526037, PubMed:16809773). During mitotic cell cycle plays a role as both substrate and inhibitor of APC-FZR1 complex (PubMed:16809773). During G1 phase, plays a role as substrate of APC-FZR1 complex E3 ligase. Then switches as an inhibitor of APC-FZR1 complex during S and G2 leading to cell-cycle commitment. As APC inhibitor, prevents the degradation of APC substrates at multiple levels: by interacting with APC and blocking access of APC substrates to the D-box co-receptor, formed by FZR1 and ANAPC10; by suppressing ubiquitin ligation and chain elongation by APC by preventing the UBE2C and UBE2S activities. Plays a role in genome integrity preservation by coordinating DNA replication with mitosis through APC inhibition in interphase to stabilize CCNA2 and GMNN in order to promote mitosis and prevent rereplication and DNA damage-induced cellular senescence (By similarity). During oocyte maturation, plays a role in meiosis through inactivation of APC-FZR1 complex. Inhibits APC through RPS6KA2 interaction that increases FBXO5 affiniy for CDC20 leading to the metaphase arrest of the second meiotic division before fertilization (PubMed:15526037). Controls entry into the first meiotic division through inactivation of APC-FZR1 complex (PubMed:17190794). Promotes migration and osteogenic differentiation of mesenchymal stem cells (By similarity).|||Ubiquitinated by the SCF(BTRC) complex following phosphorylation by PLK1. Undergoes both 'Lys-11' and 'Lys-48'-linked polyubiquitination by APC-FZR1 complex leading to degradation during G1 phase by the proteasome (By similarity). Degraded through the SCF(BTRC) complex; degradation occurs during oocyte maturation, between germinal vesicle breakdown (GVBD) and meiosis I, and is required for the meiosis I-meiosis II transition (PubMed:17190794).|||spindle http://togogenome.org/gene/10090:Cort ^@ http://purl.uniprot.org/uniprot/P56469 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatostatin family.|||Expressed in a subset of GABAergic cells in the cortex and hippocampus.|||Not induced by kainate.|||Secreted http://togogenome.org/gene/10090:Slc22a18 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0P7|||http://purl.uniprot.org/uniprot/Q78KK3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Expressed at high levels in fetal and adult kidney and liver, and extraembryonic membranes (yolk sac). Expressed at moderate levels in intestine, heart, lung and testis.|||Interacts with RNF167.|||May act as a transporter of organic cations based on a proton efflux antiport mechanism. May play a role in the transport of chloroquine and quinidine-related compounds in kidney (By similarity).|||Membrane http://togogenome.org/gene/10090:Stx1a ^@ http://purl.uniprot.org/uniprot/O35526|||http://purl.uniprot.org/uniprot/Q497P1|||http://purl.uniprot.org/uniprot/Q5D0A4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the syntaxin family.|||Cell membrane|||Expressed in the striatum (at protein level) (PubMed:17296554). Expressed in the ileum (PubMed:28596237).|||Mutant mice show impaired glucose tolerance without any marked hyperglycemia.|||Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A; this complex constitutes the basic catalytic machinery of the complex neurotransmitter release apparatus (PubMed:28031464, PubMed:19196426, PubMed:28821673). The SNARE complex interacts with CPLX1 (By similarity). Interacts with STXBP1 (PubMed:28031464, PubMed:21445306, PubMed:28821673). The interaction with STXBP1 promotes assembly of the SNARE complex (PubMed:28821673). Interacts (via C-terminus) with KCNB1 (via C-terminus); the interaction increases in a calcium-dependent manner and induces a pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons (By similarity). Interacts with SYTL4 (PubMed:12101244). Interacts with STXBP6 (By similarity). Interacts with PLCL1 (via C2 domain) (PubMed:23341457). Interacts with OTOF (PubMed:17055430). Interacts with LGI3 (PubMed:18760330). Interacts (via the H3 domain) with SLC6A4 (via the N-terminus); this interaction regulates SLC4A6 channel conductance in thalamocortical neurons (By similarity). Interacts with SYT6 and SYT8; the interaction is Ca(2+)-dependent (PubMed:15774481). Interacts with VAMP8 (PubMed:28031464). Interacts with SNAP23 (PubMed:28031464). Interacts with VAPA and SYBU (By similarity). Interacts with PRRT2 (PubMed:29056747). Interacts with SEPT8 (By similarity). Interacts with STXBP5L (PubMed:21998599). Interacts with synaptotagmin-1/SYT1 (By similarity).Interacts with SEPTIN5; in the cerebellar cortex (PubMed:17296554). Interacts with SEPTIN4; in the striatum (PubMed:17296554).|||Phosphorylated by CK2 (By similarity). Phosphorylation at Ser-188 by DAPK1 significantly decreases its interaction with STXBP1 (By similarity).|||Phosphorylated by CK2. Phosphorylation at Ser-188 by DAPK1 significantly decreases its interaction with STXBP1 (By similarity).|||Plays an essential role in hormone and neurotransmitter calcium-dependent exocytosis and endocytosis (PubMed:17502420, PubMed:28596237, PubMed:28031464). Part of the SNARE (Soluble NSF Attachment Receptor) complex composed of SNAP25, STX1A and VAMP2 which mediates the fusion of synaptic vesicles with the presynaptic plasma membrane. STX1A and SNAP25 are localized on the plasma membrane while VAMP2 resides in synaptic vesicles. The pairing of the three SNAREs from the N-terminal SNARE motifs to the C-terminal anchors leads to the formation of the SNARE complex, which brings membranes into close proximity and results in final fusion. Participates in the calcium-dependent regulation of acrosomal exocytosis in sperm (PubMed:12101244). Also plays an important role in the exocytosis of hormones such as insulin or glucagon-like peptide 1 (GLP-1) (PubMed:17502420, PubMed:28596237, PubMed:28031464).|||Sumoylated, sumoylation is required for regulation of synaptic vesicle endocytosis.|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Zscan5b ^@ http://purl.uniprot.org/uniprot/B2RTN3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rsph1 ^@ http://purl.uniprot.org/uniprot/Q8VIG3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB (PubMed:36417862, PubMed:34871179). Interacts with RSPH3B (PubMed:34871179). Interacts with RSPH4A (PubMed:34871179). Interacts with RSPH6A (PubMed:30185526, PubMed:34871179).|||Cytoplasm|||During male germ cell development it is not detected until 12 days. Significant expression is detected from 14-day-old through to adult testis. Expression is first detected in the pachytene spermatocytes at stage V, becomes stronger from the late pachytene spermatocytes to round spermatid stage, and then gradually decreases as the morphogenesis proceeds further. Not expressed in germ cells located in the first layer of the seminiferous epithelium (spermatogonia, leptotene and zygotene spermatocytes).|||Expressed in the trachea, ependymal cells, oviduct and ependymal cells (at protein level) (PubMed:32203505, PubMed:34871179). Germ cell specific. Specifically expressed in testis, and to a lower extent in ovary. Not expressed in somatic tissues (PubMed:9578619).|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Spon2 ^@ http://purl.uniprot.org/uniprot/Q8BMS2 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell adhesion protein that promotes adhesion and outgrowth of hippocampal embryonic neurons. Binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Binds bacterial lipopolysaccharide. Essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens.|||Detected in heart, lung, thymus, spleen and lymph node.|||Monomer. Interacts with integrin (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Smc5 ^@ http://purl.uniprot.org/uniprot/A0A286YDG5|||http://purl.uniprot.org/uniprot/Q8CG46 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMC family. SMC5 subfamily.|||Chromosome|||Core component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination. The complex may promote sister chromatid homologous recombination by recruiting the SMC1-SMC3 cohesin complex to double-strand breaks. The complex is required for telomere maintenance via recombination and mediates sumoylation of shelterin complex (telosome) components. Required for sister chromatid cohesion during prometaphase and mitotic progression; the function seems to be independent of SMC6 (By similarity).|||Expressed in ovary and testis at 15.5 dpc.|||Expressed in testis but not ovary.|||Forms a heterodimer with SMC6. Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. Interacts with NSMCE2. Interacts with SLF2; this interaction induces an association of the SLF1-SLF2 complex with the SMC5-SMC6 complex. Interacts with RAD18; this interaction is increased in a SLF1 or SLF2-dependent manner.|||Nucleus|||PML body|||Sumoylated.|||The flexible hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC6, forming a V-shaped heterodimer.|||Ubiquitinated.|||telomere http://togogenome.org/gene/10090:Prss50 ^@ http://purl.uniprot.org/uniprot/Q8BLH5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Although related to peptidase S1 family, lacks the conserved active Ser residue in position 364 which is replaced by a Thr.|||Belongs to the peptidase S1 family.|||May be involved in proteolysis through its threonine endopeptidase activity.|||Membrane http://togogenome.org/gene/10090:Scrn3 ^@ http://purl.uniprot.org/uniprot/Q3TMH2 ^@ Similarity ^@ Belongs to the peptidase C69 family. Secernin subfamily. http://togogenome.org/gene/10090:Pgr15l ^@ http://purl.uniprot.org/uniprot/Q80T54 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane http://togogenome.org/gene/10090:Mrpl40 ^@ http://purl.uniprot.org/uniprot/Q3UKS6|||http://purl.uniprot.org/uniprot/Q9Z2Q5 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrion-specific ribosomal protein mL40 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion|||Ubiquitous. http://togogenome.org/gene/10090:Etfa ^@ http://purl.uniprot.org/uniprot/Q99LC5 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETF alpha-subunit/FixB family.|||Binds 1 FAD per dimer.|||Domain I shares an identical polypeptide fold with the beta subunit ETFB though there is no sequence similarity.|||Expressed in the spermatogonia, spermatocytes, ovary and granular cells within the cerebellum.|||Heterodimer composed of ETFA and ETFB. Identified in a complex that contains ETFA, ETFB and ETFRF1. Interaction with ETFRF1 promotes dissociation of the bound FAD and loss of electron transfer activity (By similarity). Interacts with TASOR (PubMed:31112734).|||Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism.|||Mitochondrion matrix http://togogenome.org/gene/10090:Suv39h2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J074|||http://purl.uniprot.org/uniprot/Q9EQQ0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin (By similarity).|||Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.|||Chromosome|||Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as cell cycle regulation, transcriptional repression and regulation of telomere length. May participate in regulation of higher-order chromatin organization during spermatogenesis. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.|||In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.|||Interacts with SMAD5. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex.|||Mice lacking Suv39h1 and Suv39h2 display severely impaired viability and chromosomal instabilities that are associated with an increased tumor risk and perturbed chromosome interactions during male meiosis. They also show a higher level of histone H3 with phosphorylated 'Ser-10' and a reduced number of cells in G1 phase and an increased portion of cells with aberrant nuclear morphologies.|||Nucleus|||Strong expression in early embryos with a peak at 10.5 dpc. Expression is down-regulated at 17.5 dpc, and is nearly absent during postnatal development. In adult testes, prominent expression in late but not early spermatocytes.|||Testis specific; predominant expression in type B spermatogonia and preleptotene spermatocytes.|||Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.|||centromere http://togogenome.org/gene/10090:D130040H23Rik ^@ http://purl.uniprot.org/uniprot/Q8BII3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Tmem101 ^@ http://purl.uniprot.org/uniprot/Q91VP7 ^@ Function|||Subcellular Location Annotation ^@ May activate NF-kappa-B signaling pathways.|||Membrane http://togogenome.org/gene/10090:Atp13a1 ^@ http://purl.uniprot.org/uniprot/Q9EPE9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.|||Contains a large substrate-binding pocket that recognizes alpha-helical transmembranes, which alternately faces the endoplasmic reticulum lumen and cytosol, while remaining accessible to the lipid bilayer through a lateral opening. The translocase alternates between two conformations: inward-open (E1) and outward-open (E2) states. Undergoes a series of conformational changes with ATP-binding, phosphorylation of the Asp active site and subsequent dephosphorylation in a Post-Albers cycle (i.e., E1 -> E1-ATP -> E1P-ADP -> E1P -> E2P -> E2-Pi -> E1). A substrate transmembrane helix with a short, preferentially positively charged lumenal segment binds to the outward-open pocket and the E2P-to-E1 transition flips the transmembrane by a switch from the outward-open to inward-open conformation.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum translocase required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum. Acts as a dislocase that mediates the ATP-dependent extraction of mislocalized mitochondrial transmembrane proteins from the endoplasmic reticulum membrane. Specifically binds mitochondrial tail-anchored transmembrane proteins: has an atypically large substrate-binding pocket that recognizes and binds moderately hydrophobic transmembranes with short hydrophilic lumenal domains. http://togogenome.org/gene/10090:Hoxc6 ^@ http://purl.uniprot.org/uniprot/B2RUB8|||http://purl.uniprot.org/uniprot/P10629|||http://purl.uniprot.org/uniprot/Q543H4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Spry1 ^@ http://purl.uniprot.org/uniprot/Q9QXV9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 8.5 dpc, expressed in the primitive streak, rostral forebrain, cells lateral to the posterior hindbrain, anterior hindbrain and developing midbrain (PubMed:10498682). At 9.5 dpc, continues to be expressed in the rostral forebrain and primitive streak, and is also detected in the branchial arches and the forelimb bud (PubMed:10498682). At 10.5 dpc, expressed in the somites, frontonasal processes, tailbud, and hindlimb bud (PubMed:10498682).|||Belongs to the sprouty family.|||Cytoplasm|||Forms heterodimers with SPRY2 (PubMed:16877379). Interacts with TESK1 (PubMed:17974561). Interacts with CAV1 (via C-terminus) (PubMed:16877379).|||Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (PubMed:29501879). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (PubMed:25576668).|||Membrane|||The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles. http://togogenome.org/gene/10090:Prf1 ^@ http://purl.uniprot.org/uniprot/A2RSY7|||http://purl.uniprot.org/uniprot/P10820 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the complement C6/C7/C8/C9 family.|||Cell membrane|||Cytolytic granule|||Detected in cytotoxic T-lymphocytes and natural killer cells.|||Endosome lumen|||Mice are viable and fertile, but die of virus infections that are normally efficiently dealt with by the immune system (PubMed:7526382, PubMed:8164737, PubMed:7972104, PubMed:7520535). They cannot eliminate lymphocytic choriomeningitis virus, but die of the infection (PubMed:7526382, PubMed:8164737, PubMed:7972104, PubMed:7520535). Young mice are abnormally susceptible to mouse hepatitis virus (PubMed:7526382, PubMed:8164737, PubMed:7972104, PubMed:7520535). Cytolytic activity towards tumor cells and transplants is also severely reduced (PubMed:7526382, PubMed:8164737, PubMed:7972104, PubMed:7520535).|||Monomer, as soluble protein (PubMed:19446473, PubMed:21037563). Homooligomer; homooligomerizes to form a pore-forming ring (PubMed:19446473, PubMed:21037563, PubMed:35148176).|||N-glycosylated. The glycosylation sites are facing the interior of the pore.|||Perforin consists of three domains: (1) the MACPF domain, which includes the central machinery of pore formation, (2) the EGF-like domain, which forms a 'shelf-like' assembly connecting the MACPF and C2 domains, and (3) the C2 domain, which mediates calcium-dependent binding to lipid membranes (PubMed:21037563, PubMed:35148176). The C2 domain is critical for initial calcium-dependent interaction with lipid membranes of the target cell: calcium-binding causes a significant structural rearrangement, leading to oligomerization and deployment of the two transmembrane beta-strands (named CH1/TMH1 and CH2/TMH2) that enter the membrane as amphipathic beta-hairpins (PubMed:21037563, PubMed:26306037, PubMed:35148176). The third calcium-binding site (Ca(2+) 3), which constitutes the weakest affinity site, triggers structural rearrangements in the C2 domain that facilitate its interaction with lipid membranes (PubMed:26306037).|||Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:2783478, PubMed:7520535, PubMed:7972104, PubMed:19446473, PubMed:21037563, PubMed:3261391, PubMed:7526382, PubMed:8164737, PubMed:26306037, PubMed:35148176, PubMed:35705808). Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores (PubMed:19446473, PubMed:21037563, PubMed:3261391, PubMed:7526382, PubMed:8164737, PubMed:26306037, PubMed:35148176, PubMed:35705808). Promotes cytolysis and apoptosis of target cells by mediating the passage and uptake of cytotoxic granzymes (PubMed:19446473, PubMed:21037563, PubMed:3261391, PubMed:7526382, PubMed:8164737, PubMed:26306037, PubMed:35148176). Facilitates the delivery of cationic cargo protein, while anionic or neural proteins are not delivered efficiently (By similarity). Perforin pores allow the release of mature caspase-7 (CASP7) into the extracellular milieu (PubMed:35705808).|||Secreted http://togogenome.org/gene/10090:Or52n2b ^@ http://purl.uniprot.org/uniprot/Q7TRP4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fermt1 ^@ http://purl.uniprot.org/uniprot/P59113 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the kindlin family.|||Interacts with the cytoplasmic domain of integrins ITGB1 and ITGB3.|||Involved in cell adhesion. Contributes to integrin activation. When coexpressed with talin, potentiates activation of ITGA2B. Required for normal keratinocyte proliferation. Required for normal polarization of basal keratinocytes in skin, and for normal cell shape. Required for normal adhesion of keratinocytes to fibronectin and laminin, and for normal keratinocyte migration to wound sites (By similarity).|||Mice are born with the expected Mendelian distribution and appear normal at birth, but fail to thrive, become dehydrated and die after three to five days. They develop skin atrophy and die due to a lethal intestinal epithelial dysfunction. The colon is shortened and swollen and presents signs of acute inflammation. At the time of death, about 80% of the colonic epithelium is detached.|||The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain. The FERM domain contains the subdomains F1, F2 and F3. It is preceded by a F0 domain with a ubiquitin-like fold. The F0 domain is required for integrin activation and for localization at focal adhesions (By similarity).|||cytoskeleton|||focal adhesion|||ruffle membrane http://togogenome.org/gene/10090:Sepsecs ^@ http://purl.uniprot.org/uniprot/Q6P6M7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SepSecS family.|||Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis.|||Cytoplasm|||Homotetramer formed by a catalytic dimer and a non-catalytic dimer serving as a binding platform that orients tRNASec for catalysis. Each tetramer binds the CCA ends of two tRNAs which point to the active sites of the catalytic dimer (By similarity). http://togogenome.org/gene/10090:Cxcl13 ^@ http://purl.uniprot.org/uniprot/O55038|||http://purl.uniprot.org/uniprot/Q3U1E8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Found in spleen (B-cell-rich zone or follicles), Peyer patches (strongest within germinal centers and extending to the mantle zone) and lymph nodes (in reticular pattern in follicles).|||Secreted|||Strongly chemotactic for B-lymphocytes, weakly for spleen monocytes and macrophages but no chemotactic activity for granulocytes. Binds to BLR1/CXCR5. May play a role in directing the migration of B-lymphocytes to follicles in secondary lymphoid organs. http://togogenome.org/gene/10090:Lrrc8a ^@ http://purl.uniprot.org/uniprot/Q80WG5 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRC8 family.|||Cell membrane|||Defects in Lrrc8a are the cause of ebouriffe (ebo), a spontaneous mutation that causes male sterility (PubMed:8828840, PubMed:28192143, PubMed:30135305). Spermatozoa present in the epididymis display severe malformations, mostly of the tail (PubMed:8828840, PubMed:28192143). A drastic decrease of the spermatid population is observed, whereas spermatogonia and spermatocytes seem moderately affected (PubMed:8828840, PubMed:28192143). Defects are caused by decreased volume-regulated anion channel (VRAC) activity in germ cells (PubMed:30135305). Oogenesis is not affected but embryos derived from ebo/ebo females show early developmental failure (PubMed:30135305).|||Essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:30135305, PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (By similarity). In complex with LRRC8C or LRRC8E, acts as a transporter of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol: mediates both import and export of 2'-3'-cGAMP, thereby promoting transfer of 2'-3'-cGAMP to bystander cells (PubMed:32277911). In contrast, complexes containing LRRC8D inhibit transport of 2'-3'-cGAMP (By similarity). Required for in vivo channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (By similarity). Can form functional channels by itself (in vitro) (By similarity). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746, PubMed:24752297). Also required for T-cell development (PubMed:24752297). Required for myoblast differentiation: VRAC activity promotes membrane hyperpolarization and regulates insulin-stimulated glucose metabolism and oxygen consumption (PubMed:31387946, PubMed:32930093). Also acts as a regulator of glucose-sensing in pancreatic beta cells: VRAC currents, generated in response to hypotonicity- or glucose-induced beta cell swelling, depolarize cells, thereby causing electrical excitation, leading to increase glucose sensitivity and insulin secretion (PubMed:29371604, PubMed:29773801). Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis (By similarity).|||Hexamer; forms a trimer of dimers (PubMed:29769723, PubMed:30775971). Heterohexamer; oligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:29769723). Can form homohexamers in vitro, but these have lower conductance than heterohexamers (PubMed:29769723). Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity). In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable). Interact with GRB2 (PubMed:32930093).|||Increased prenatal and postnatal mortality, growth retardation, and multiple tissue abnormalities (PubMed:24752297). B-cell development is slightly impaired, without affecting B-cell function (PubMed:24752297). Mice however show a cell-autonomous early block in thymocyte development and impairs peripheral T-cell expansion and function (PubMed:24752297). Conditional deletion in germ cells leads to abnormal sperm and male infertility: the cytoplasm of late spermatids appears swollen, preventing reduction of the cytoplasm during further development into spermatozoa (PubMed:29880644, PubMed:30135305). Spermatozoa display severely disorganized mitochondrial sheaths in the midpiece region, as well as angulated or coiled flagella, resulting in dramatically reduced sperm motility (PubMed:29880644). Conditional deletion in Sertoli cells does not affect male fertility (PubMed:29880644). Conditional deletion in pancreatic beta cells have normal resting serum glucose levels but impaired glucose tolerance (PubMed:29371604, PubMed:29773801). Conditional deletion in myotubes leads to impaired myoblast differentiation: mice have smaller myofibers, generate less force ex vivo, and display reduced exercise endurance, associated with increased adiposity under basal conditions, and glucose intolerance and insulin resistance when raised on a high-fat diet (PubMed:32930093).|||Inhibited by (4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid), which plugs the channel like a cork in a bottle by binding in the extracellular selectivity filter and sterically occluding ion conduction.|||Lysosome membrane|||N-glycosylated.|||The cytoplasmic N-terminus preceding the first transmembrane (residues 1-22) regulates volume-regulated anion channel (VRAC) conductance, ion permeability and inactivation gating.|||The di-leucine motif is required for lysosomal localization.|||The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins.|||Ubiquitously expressed (PubMed:24725410, PubMed:30135305). High levels detected in the bone marrow; lower levels found in peripheral blood cells (PubMed:14660746, PubMed:15094057, PubMed:24752297). Highly expressed in pancreatic beta cells (PubMed:29773801). http://togogenome.org/gene/10090:Pdpk1 ^@ http://purl.uniprot.org/uniprot/F2Z3X6|||http://purl.uniprot.org/uniprot/Q3TRL2|||http://purl.uniprot.org/uniprot/Q3UGN6|||http://purl.uniprot.org/uniprot/Q3UHZ0|||http://purl.uniprot.org/uniprot/Q9Z2A0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.|||Cell membrane|||Cytoplasm|||Highly expressed in heart, brain, liver and testis, also expressed in embryonic cells.|||Homodimer in its autoinhibited state. Active as monomer. Interacts with NPRL2, PAK1, PTK2B, GRB14, STRAP and IKKB. The Tyr-9 phosphorylated form interacts with SRC, RASA1 and CRK (via their SH2 domains). Interacts with SGK3 in a phosphorylation-dependent manner. The tyrosine-phosphorylated form interacts with PTPN6. The Ser-244 phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and SMAD7. Interacts with PKN2; the interaction stimulates PDPK1 autophosphorylation, its PI(3,4,5)P3-dependent kinase activity toward 'Ser-473' of AKT1 but also activates its kinase activity toward PRKCD and PRKCZ (By similarity). Interacts with PKN1 (via C-terminus) and PPARG.|||Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-376 and Tyr-379 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-244 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-376 and Tyr-379 by INSR in response to insulin (By similarity).|||Mice show severe pancreatic hypoplasia at birth and ensuing hyperglycemia at postnatal stages and die of heart failure by 11 weeks of age.|||Monoubiquitinated in the kinase domain, deubiquitinated by USP4.|||Nucleus|||Phosphorylation on Ser-244 in the activation loop is required for full activity. PDPK1 itself can autophosphorylate Ser-244, leading to its own activation. Autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 (By similarity). Tyr-9 phosphorylation is critical for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90-mediated protection of PDPK1 degradation. Angiotensin II stimulates the tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-376 and Tyr-379 by INSR in response to insulin. Palmitate negatively regulates autophosphorylation at Ser-244 and palmitate-induced phosphorylation at Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylation at Thr-357 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity).|||Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages.|||The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization.|||The PIF-pocket is a small lobe in the catalytic domain required by the enzyme for the binding to the hydrophobic motif of its substrates. It is an allosteric regulatory site that can accommodate small compounds acting as allosteric inhibitors.|||focal adhesion http://togogenome.org/gene/10090:Rhox10 ^@ http://purl.uniprot.org/uniprot/Q4TU83 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Guk1 ^@ http://purl.uniprot.org/uniprot/E9Q7K1|||http://purl.uniprot.org/uniprot/Q64520 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the guanylate kinase family.|||Catalyzes the phosphorylation of GMP to GDP. Essential enzyme for recycling GMP and indirectly, cyclic GMP (cGMP) (PubMed:8663313). Involved in the cGMP metabolism in photoreceptors (By similarity).|||Monomer (By similarity). Interacts with RD3 (By similarity).|||Photoreceptor inner segment|||Widely expressed (PubMed:8663313). In retina is expressed in inner segment, outer nuclear layer, outer plexiform layer, inner plexiform layer, and ganglion cell layer (at protein level) (PubMed:29515371).|||cytosol http://togogenome.org/gene/10090:Fam114a2 ^@ http://purl.uniprot.org/uniprot/Q8VE88 ^@ Similarity ^@ Belongs to the FAM114 family. http://togogenome.org/gene/10090:Rev3l ^@ http://purl.uniprot.org/uniprot/Q61493 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-B family.|||Binds 1 [4Fe-4S] cluster.|||Catalytic subunit of the DNA polymerase zeta complex, an error-prone polymerase specialized in translesion DNA synthesis (TLS). Lacks an intrinsic 3'-5' exonuclease activity and thus has no proofreading function.|||Heterodimer with MAD2L2. This dimer forms the minimal DNA polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase catalytic activity, although its activity is very low in this context. Component of the tetrameric Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is the fully active form of DNA polymerase zeta.|||Nucleus|||The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes. http://togogenome.org/gene/10090:Zcchc3 ^@ http://purl.uniprot.org/uniprot/Q8BPK2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CGAS (By similarity). Interacts with RIGI (By similarity). Interacts with IFIH1/MDA5 (By similarity).|||Mice were born at the Mendelian ratio and do not show defects in development and immune cell differentiation (PubMed:30193849). Mice are however more susceptible to DNA and RNA virus infection (PubMed:30193849, PubMed:30135424).|||Nucleic acid-binding protein involved in innate immune response to DNA and RNA viruses (PubMed:30193849, PubMed:30135424). Binds DNA and RNA in the cytoplasm and acts by promoting recognition of viral nucleic acids by virus sensors, such as RIGI, IFIH1/MDA5 and CGAS (PubMed:30193849, PubMed:30135424). Acts as a co-sensor for recognition of double-stranded DNA (dsDNA) by cGAS in the cytoplasm, thereby playing a role in innate immune response to cytosolic dsDNA and DNA virus (By similarity). Binds dsDNA and probably acts by promoting sensing of dsDNA by CGAS, leading to enhance CGAS oligomerization and activation (By similarity). Promotes sensing of viral RNA by RIG-I-like receptors proteins RIGI and IFIH1/MDA5 via two mechanisms: binds double-stranded RNA (dsRNA), enhancing the binding of RIGI and IFIH1/MDA5 to dsRNA and promotes 'Lys-63'-linked ubiquitination and subsequent activation of RIGI and IFIH1/MDA5 (By similarity). http://togogenome.org/gene/10090:Ybx3 ^@ http://purl.uniprot.org/uniprot/Q9JKB3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the GM-CSF promoter. Seems to act as a repressor (By similarity). Binds also to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression.|||Cytoplasm|||Expressed in oocytes, spermatocytes and spermatids (at protein level). Expressed in skeletal muscle, kidney, brain, spleen, liver, heart and spermatids. Isoform 2 is preferentially expressed in somatic tissues (PubMed:10956549).|||Found in a mRNP complex with YBX2 (PubMed:10772793). Interacts with RRP1B (By similarity).|||Nucleus|||Transgenic mice overexpressing Ybx3 exhibit disruption of the normal completion of spermatogenesis, dominant sterility and abnormal translation activation of repressed mRNA. http://togogenome.org/gene/10090:Man1a ^@ http://purl.uniprot.org/uniprot/P45700|||http://purl.uniprot.org/uniprot/Q544T7 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 47 family.|||Golgi apparatus membrane|||Inhibited by both 1-deoxymannojirimycin and kifunensine.|||Involved in the maturation of Asn-linked oligosaccharides. Progressively trim alpha-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2).|||N-linked glycan at Asn-515 consists of Man(6)-GlcNAc(2). http://togogenome.org/gene/10090:Sncg ^@ http://purl.uniprot.org/uniprot/Q5GQ64|||http://purl.uniprot.org/uniprot/Q9Z0F7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synuclein family.|||Developmentally expressed in primary sensory neurons and motoneurons. In trigeminal ganglia, expression increases between embryonic day 10 and day 12. High levels are maintained here throughout later stages of development and in adulthood.|||Highly expressed in brain, particularly in the substantia nigra. Also expressed in the corpus callosum, heart, skeletal muscle, ovary, testis, colon and spleen. Weak expression in pancreas, kidney and lung. Expressed predominantly in the cell bodies and axons of primary sensory neurons, sympathetic neurons and motoneurons.|||May be a centrosome-associated protein. Interacts with MYOC; affects its secretion and its aggregation.|||Phosphorylated. Phosphorylation by GRK5 appears to occur on residues distinct from the residue phosphorylated by other kinases (By similarity).|||Plays a role in neurofilament network integrity. May be involved in modulating axonal architecture during development and in the adult. In vitro, increases the susceptibility of neurofilament-H to calcium-dependent proteases. May also function in modulating the keratin network in skin. Activates the MAPK and Elk-1 signal transduction pathway (By similarity).|||Simultaneous knockout of SNCA, SNCB and SNCG exhibit an age-dependent decrease in SNARE-complex assembly. Thus, synucleins are required for maintaining normal SNARE-complex assembly during aging in mice.|||centrosome|||perinuclear region|||spindle http://togogenome.org/gene/10090:Emcn ^@ http://purl.uniprot.org/uniprot/Q9R0H2 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Endothelial sialomucin, also called endomucin or mucin-like sialoglycoprotein, which interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix.|||Highly O-glycosylated. Sialic acid-rich glycoprotein.|||Highly expressed in heart and kidney, followed by brain, spleen, thymus, liver and lung. Exclusively expressed in endothelial cells.|||Membrane http://togogenome.org/gene/10090:Ncf1 ^@ http://purl.uniprot.org/uniprot/Q09014 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts (via C-terminus) with NCF2 (via the C-terminal SH3 domain). Interacts with NCF4. Interacts with CYBB. Interacts (via the second SH3 domain) with CYBA. Interacts with NOXA1. Interacts with ADAM15. Interacts with TRAF4. Interacts with FASLG (By similarity). Interacts with PARK7 (via C-terminus); the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (PubMed:26021615).|||Membrane|||NCF2, NCF1, and a membrane bound cytochrome b558 are required for activation of the latent NADPH oxidase (necessary for superoxide production).|||Phosphorylated by PRKCD; phosphorylation induces activation of NCF1 and NADPH oxidase activity.|||The PX domain mediates interaction with phosphatidylinositol 3,4-bisphosphate and other anionic phospholipids. In the autoinhibited, unphosphorylated state an intramolecular interaction with the C-terminal SH3 domain precludes phospholipid binding and interaction with CYBA. Phosphorylation disrupts the autoinhibited state (By similarity).|||cytosol http://togogenome.org/gene/10090:Itih4 ^@ http://purl.uniprot.org/uniprot/A0A2K6EDJ7|||http://purl.uniprot.org/uniprot/A6X935|||http://purl.uniprot.org/uniprot/E9PVD2|||http://purl.uniprot.org/uniprot/E9Q5L2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ITIH family.|||During mid-embryonic gestation, expressed abundantly in liver, less in heart and brain. Highest expression at day 14.5.|||Highly expressed in liver. Weak expression in lung and heart.|||Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain).|||May be O-glycosylated (By similarity). N-glycosylated.|||Secreted|||Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration. http://togogenome.org/gene/10090:Fcrl2 ^@ http://purl.uniprot.org/uniprot/Q9EQY5 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Abhd17b ^@ http://purl.uniprot.org/uniprot/Q7M759 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. ABHD17 family.|||Cell membrane|||Expressed in brain.|||Hydrolyzes fatty acids from S-acylated cysteine residues in proteins (PubMed:27307232). Has depalmitoylating activity towards DLG4/PSD95 (PubMed:27307232). Has depalmitoylating activity towards GAP43 (PubMed:27307232). Has depalmitoylating activity towards MAP6 (PubMed:28521134). Has depalmitoylating activity towards NRAS (By similarity).|||Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization. Palmitoylation is required for post-synaptic localization and for depalmitoylating activity towards DLG4/PSD95.|||Postsynaptic density membrane|||Recycling endosome membrane|||dendritic spine http://togogenome.org/gene/10090:Faap100 ^@ http://purl.uniprot.org/uniprot/A2ACJ2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9, FANCM, FAAP24 and FAAP100. Forms a subcomplex with FANCB and FANCL (By similarity).|||Nucleus|||Plays a role in Fanconi anemia-associated DNA damage response network. Regulates FANCD2 monoubiquitination and the stability of the FA core complex. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed (By similarity). http://togogenome.org/gene/10090:Banf2 ^@ http://purl.uniprot.org/uniprot/Q8BVR0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Heterodimerizes with BANF1 (By similarity).|||May play a role in BANF1 regulation and influence tissue-specific roles of BANF1.|||Nucleus http://togogenome.org/gene/10090:Msh2 ^@ http://purl.uniprot.org/uniprot/P43247|||http://purl.uniprot.org/uniprot/Q3TZI5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA mismatch repair MutS family.|||Chromosome|||Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimers form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with MCM9; the interaction recruits MCM9 to chromatin. Interacts with MCM8. Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases. Interacts with SMARCAD1.|||Component of the post-replicative DNA mismatch repair system (MMR).|||Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containing DNA strand. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis.|||Nucleus http://togogenome.org/gene/10090:Soga3 ^@ http://purl.uniprot.org/uniprot/Q6NZL0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SOGA family.|||Membrane http://togogenome.org/gene/10090:Arpp21 ^@ http://purl.uniprot.org/uniprot/Q9DCB4 ^@ Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Down-regulated in thymocytes upon TCR engagement (at protein level).|||Interacts with CALM1.|||May act as a competitive inhibitor of calmodulin-dependent enzymes such as calcineurin in neurons.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Methylated by CARM1 at Arg-650 in immature thymocytes.|||Phosphorylation of isoform 2 at Ser-55 is enhanced upon dopamine D1 receptor activation and favors interaction with CALM1.|||Present at high levels in thymus and low levels in brain. In thymus, isoform 1 is specifically found in immature thymocytes (at protein level). http://togogenome.org/gene/10090:Spc24 ^@ http://purl.uniprot.org/uniprot/Q9D083 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules.|||Belongs to the SPC24 family.|||Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end (By similarity).|||Nucleus|||kinetochore http://togogenome.org/gene/10090:Rprd1b ^@ http://purl.uniprot.org/uniprot/A0A0R4J195|||http://purl.uniprot.org/uniprot/Q9CSU0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the RNA polymerase II complex.|||Belongs to the UPF0400 (RTT103) family.|||Highly expressed during early embryonic development (at protein level). Low levels detected in the adult.|||Homodimer. May form a heterodimer with RPRD1A. Associates with RPAP2. Associates with the RNA polymerase II complex.|||Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. Transcriptional regulator which enhances expression of CCND1. Promotes binding of RNA polymerase II to the CCDN1 promoter and to the termination region before the poly-A site but decreases its binding after the poly-A site. Prevents RNA polymerase II from reading through the 3' end termination site and may allow it to be recruited back to the promoter through promotion of the formation of a chromatin loop. Also enhances the transcription of a number of other cell cycle-related genes including CDK2, CDK4, CDK6 and cyclin-E but not CDKN1A, CDKN1B or cyclin-A. Promotes cell proliferation.|||Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD.|||Nucleus|||Widely expressed in the adult with highest levels in liver, colon, prostate and uterus and lowest levels in heart and kidney. Not detected in rectum. http://togogenome.org/gene/10090:Hnrnpa0 ^@ http://purl.uniprot.org/uniprot/Q9CX86 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Arg-293 is dimethylated, probably to asymmetric dimethylarginine.|||Nucleus|||Phosphorylated at Ser-84 by MAPKAPK2 in response to LPS treatment, promoting stabilization of GADD45A mRNA.|||mRNA-binding component of ribonucleosomes. Specifically binds AU-rich element (ARE)-containing mRNAs. Involved in post-transcriptional regulation of cytokines mRNAs. http://togogenome.org/gene/10090:Mansc4 ^@ http://purl.uniprot.org/uniprot/Q3UU94 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pprc1 ^@ http://purl.uniprot.org/uniprot/Q6NZN1 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a coactivator during transcriptional activation of nuclear genes related to mitochondrial biogenesis and cell growth. Involved in the transcription coactivation of CREB and NRF1 target genes (By similarity).|||Expressed in liver, heart, skeletal muscle, kidney and white and brown adipose tissues.|||Interacts with CREB1 and NRF1.|||Nucleus|||Up-regulated by serum (at protein level). Up-regulated by serum. Up-regulated weakly in brown adipose tissue by exposure of animals to cold. http://togogenome.org/gene/10090:Usp12 ^@ http://purl.uniprot.org/uniprot/Q9D9M2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by interaction with WDR20 and WDR48 through different allosteric mechanisms.|||Belongs to the peptidase C19 family. USP12/USP46 subfamily.|||Cell membrane|||Cytoplasm|||Deubiquitinating enzyme that plays various roles in the regulation of the immune response and inflammation. In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability. During TCR engagement and activation, translocates into the cytoplasm and deubiquitinates its substrates LAT and TRAT1 and prevents their lysosome-dependent degradation to stabilize the TCR signaling complex at the plasma membrane. Plays an essential role in the selective LPS-induced macrophage response through the activation of NF-kappa-B pathway. In addition, promotes that antiviral immune response through targeting DNA sensor IFI16 to inhibit its proteasome-dependent degradation. Participates in the interferon signaling pathway and antiviral response independently of its deubiquitinase activity by maintaining nuclear phosphorylated STAT1 levels via inhibition of its CREBBP-mediated acetylation and subsequent dephosphorylation (By similarity). Plays an intrinsic role in promoting the differentiation, activation and proliferation of CD4(+) T-cell by activating the NF-kappa-B signaling pathway through deubiquitinating and stabilizing B-cell lymphoma/leukemia 10/BCL10 (PubMed:33941870). In myeloid-derived suppressor cells promotes the activation of the NF-kappa-B via deubiquitination and stabilization of RELA (PubMed:35898171). Regulates the 'Lys-63'-linked polyubiquitin chains of BAX and thereby modulates the mitochondrial apoptotic process (By similarity).|||Interacts with WDR48. Interacts with WDR20; this interaction promotes translocation of the USP12 complex to the plasma membrane. Component of the USP12/WDR20/WDR48 deubiquitinating complex. Interacts with PHLPP1. Interacts with RBPJ. Interacts with CBP; this interaction blocks the acetyltransferase activity of CREBBP.|||Nucleus|||USP12-deficiency attenuates CD4(+) T-cell activation (PubMed:33941870). In addition, USP12 mutant mice show significantly reduced tumor growth when compared to WT mice. Both the frequency and number of CD4(+) or CD8(+) T-cells isolated from the tumor are significantly higher in the USP12-deletion mutant mice (PubMed:35898171). http://togogenome.org/gene/10090:Bst1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J190|||http://purl.uniprot.org/uniprot/Q64277 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ADP-ribosyl cyclase family.|||Catalyzes both the synthesis of cyclic ADP-beta-D-ribose (cADPR) from NAD(+), and its hydrolysis to ADP-D-ribose (ADPR). Cyclic ADPR is known to serve as an endogenous second messenger that elicits calcium release from intracellular stores, and thus regulates the mobilization of intracellular calcium. May be involved in pre-B-cell growth.|||Cell membrane|||Expressed in the bone marrow, spleen and thymus in lymphoid organs, and the lung, kidney and heart in non-lymphoid organs.|||Homodimer. http://togogenome.org/gene/10090:Col28a1 ^@ http://purl.uniprot.org/uniprot/Q2UY11 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VWA-containing collagen family.|||Expressed in skin, intestine, sternum, brain and kidney. Lower expression is also observed in heart, lung, sciatic nerve, dorsal root ganglia, peripheral nerves and calvaria of newborn mice and in intestine and brain of adult mice. Found in basement membrane surrounding a particular subset of Schwann cells in adult sciatic nerve.|||Major expression in dorsal root ganglia and peripheral nerves, with small amounts in connective tissues like calvaria and skin.|||May act as a cell-binding protein.|||Trimer or homomer. Secreted into as a 135 kDa monomer under reducing conditions and as a homotrimer under non-reducing conditions.|||basement membrane http://togogenome.org/gene/10090:Cdc34 ^@ http://purl.uniprot.org/uniprot/Q8CFI2 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin.|||Belongs to the ubiquitin-conjugating enzyme family.|||CDC34-catalyzed polyubiquitin chain assembly activity is stimulated by the conjugation of NEDD8 to the CUL1 SCF E3 ligase complex subunit.|||Cytoplasm|||Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and RBX1. When cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened (By similarity). When phosphorylated, interacts with beta-TrCP (BTRC) (By similarity). Interacts with casein kinase subunit CSNK2B. Interacts with CNTD1; this interaction regulates the cell-cycle progression (PubMed:32640224).|||Nucleus|||Phosphorylated by CK2. Phosphorylation of the C-terminal tail by CK2 controls the nuclear localization.|||The C-terminal acidic tail is required for nuclear localization and is involved in the binding to SCF E3 ligase complexes, and more specifically with the CUL1 subunit. http://togogenome.org/gene/10090:Ctnna2 ^@ http://purl.uniprot.org/uniprot/Q61301 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the vinculin/alpha-catenin family.|||Cell membrane|||Cytoplasm|||Expressed almost exclusively in the nervous system.|||Interacts with CDH1 and CDH2 (By similarity). Interacts with ZNF639; recruits CTNNA2 to the nucleus (By similarity). Interacts with F-actin (By similarity).|||May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (PubMed:12123610, PubMed:15034585). Required for proper regulation of cortical neuronal migration and neurite growth. It acts as negative regulator of Arp2/3 complex activity and Arp2/3-mediated actin polymerization. It thereby suppresses excessive actin branching which would impair neurite growth and stability (By similarity). Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in the control of startle modulation (PubMed:12089526).|||Mice generally die within 24 hours after birth. They display altered Purkinje cells migration, unstable synaptic junctions, defective ventricular architecture, impaired axon migration, reduced number of neurons in specific nuclei, and disordered laminar formation.|||Nucleus|||The cdf (cerebellar deficient folia) mice are viable but are ataxic and have cerebellar hypoplasia associated with abnormal lobulation of the cerebellum. They also display defects in Purkinje cells positioning and in packing density and lamination. Fear conditioning and prepulse inhibition of the startle response are altered in cdf mice. Those phenotypes are associated with alteration of the Ctnna2 gene which results in the C-terminal truncation of the protein and are rescued by expression of a Ctnna2 transgene (isoform 2).|||The ratio of the two isoforms changes during development; isoform 1 is more abundant than isoform 2 in earlier embryonic stages, whereas isoform 2 is predominant in the adult stage. Expressed in the ventricular zone and in neurons of the developing cortical plate (at protein level). Expressed in migrating neurons of the external granule cell layer at 13.5 dpc while expression appears in the Purkinje cell layer at 17.5 dpc (at protein level). Expressed postnatally in Purkinje cells and hippocampus (at protein level).|||adherens junction|||axon|||cytoskeleton http://togogenome.org/gene/10090:Olfm3 ^@ http://purl.uniprot.org/uniprot/P63056|||http://purl.uniprot.org/uniprot/Q3UVC5 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed during embryonic development starting from 7 dpc. Expression increases moderately during embryonic development and remains stable in the postnatal brain.|||Expressed in the brain (at protein level).|||Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including OLFM3. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (PubMed:22632720). Homodimer. Interacts with MYOC (PubMed:12019210). Interacts with OLFM2 (By similarity).|||Secreted|||Synapse http://togogenome.org/gene/10090:Smtnl1 ^@ http://purl.uniprot.org/uniprot/Q99LM3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the smoothelin family.|||I band|||Interacts with PPP1R12A.|||M line|||Male mutant mice perform better than wild type in exercise stress test after endurance training. Females do not differ significantly during these tests. Even in the absence of endurance exercise, mutant mice exhibit muscle fiber adaptation, i.e. more type 2a fibers and lower levels of type 1b fibers. Endothelium-dependent vasorelaxation of the aorta is enhanced and responses to beta-adrenergic constriction are reduced. Expression of PPP1R12A is 30-40-fold higher in mutant mice than in wild-type littermates and exhibits a steady decline as the animals become sexually mature (at protein level). During pregnancy, by day 13, PPP1R12A expression is dramatically increased to 6-14 times over the levels observed in pregnant wild-type littermates (at protein level). PPP1R12B expression levels are unaffected. In vascular smooth muscle, force development in response to phenylephrine is reduced and both the rate and extent of relaxation in response to acetylcholine are promoted. Myosin dephosphorylation is promoted in mutant animals.|||Maximal phosphorylation of Ser-301 correlates with maximal relaxation of aorta in response to acetylcholine.|||Not detected in somites which give rise to skeletal muscle at 10.5 dpc (at protein level). Expressed in skeletal muscle of the tongue, diaphragm and axial muscles from 14.5 through 17.5 dpc (at protein level). Not detected in limb buds (at protein level). Overall increase by up to 10-12-fold in vascular and uterine smooth muscle during pregnancy (at protein level). At day 13 of pregnancy, expression increases in striated muscle by 2.5-fold compared with non-pregnant mice, and by about 2-fold over levels expressed in males (at protein level). At the same time, dramatically increased in myometrial cells of the uterus, in the endometrial layer and in aortal smooth muscle. Steadily declines through parturition and the onset of lactation (at protein level).|||Nucleus|||Plays a role in the regulation of contractile properties of both striated and smooth muscles. When unphosphorylated, may inhibit myosin dephosphorylation. Phosphorylation at Ser-301 reduces this inhibitory activity.|||Significantly reduced by exercise in smooth and in skeletal muscles.|||Widely expressed, with highest expression in skeletal muscles (at protein level). Within striated muscles, significantly more expressed in soleus muscle compared with plantaris muscle or white vastus (at protein level). 30-40% lower expression in females than in males (at protein level). Expressed in type 2a fibers, but not detected in fast twitch type 2b muscle white vastus nor in oxidative type I/b heart muscle (at protein level). Expressed within myometrial cells of the uterus, as well as in the endometrial layer. In the aorta, confined to smooth muscle cells. Not detected in endothelial cells. http://togogenome.org/gene/10090:Sin3b ^@ http://purl.uniprot.org/uniprot/Q3TN09|||http://purl.uniprot.org/uniprot/Q62141 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression (PubMed:22476904).|||Interacts with FOXK1/MNF, MXI, MAD, NCOR1 and SAP30. Interaction with SUDS3 enhances the interaction with HDAC1 to form a complex. Interacts with CRY1, HCFC1, MAD3, MAD4, MAEL, REST, RNF220 and SETDB1. Interacts with MYT1L (PubMed:28379941). Interacts with C6orf89 (By similarity).|||Nucleus|||Ubiquitinated by RNF220 that leads to proteasomal degradation. http://togogenome.org/gene/10090:Car9 ^@ http://purl.uniprot.org/uniprot/Q3UUZ9|||http://purl.uniprot.org/uniprot/Q8VHB5 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Asn-325 bears high-mannose type glycan structures.|||Belongs to the alpha-carbonic anhydrase family.|||Catalyzes the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions).|||Cell membrane|||Forms oligomers linked by disulfide bonds.|||Inhibited by acetazolamide.|||Nucleus|||Reversible hydration of carbon dioxide.|||microvillus membrane|||nucleolus http://togogenome.org/gene/10090:Cd2 ^@ http://purl.uniprot.org/uniprot/P08920|||http://purl.uniprot.org/uniprot/Q549Q4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function.|||Cell membrane|||Detected in thymus and spleen.|||Interacts with CD48 (By similarity). Interacts with CD58 (LFA-3) (By similarity). Interacts with CD2AP (PubMed:9741631). Interacts with PSTPIP1 (PubMed:12530983). Interacts with FCGR3A; this interaction modulates NK cell activation and cytotoxicity.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Magi2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JE00|||http://purl.uniprot.org/uniprot/A0A0G2JEG6|||http://purl.uniprot.org/uniprot/Q9WVQ1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAGUK family.|||Cell membrane|||Cytoplasm|||Expressed throughout the retina except in the nuclear layers and the photoreceptor outer segments (at protein level) (PubMed:24608321). Highest retinal expression is observed in the outer plexiform layer, the outer limiting membrane and the inner segment of photoreceptor cells (at protein level) (PubMed:24608321). Expressed in brain.|||Interacts (via its WW domains) with DRPLA (By similarity). Interacts (via its second PDZ domain) with PTEN (via unphosphorylated C-terminus); this interaction diminishes the degradation rate of PTEN (By similarity). Interacts (via guanylate kinase domain) with DLGAP1 (By similarity). Interacts (via the PDZ domains) with GRIN2A, GRID2 and NLGN1 (By similarity). Interacts with CTNND2, CTNNB1 and MAGUIN-1 (By similarity). Interacts with ACVR2A, SMAD2 and SMAD3 (PubMed:10681527). Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:10681527). May interact with HTR2A (PubMed:14988405). Interacts with RAPGEF2 (By similarity). Identified in a complex with ACTN4, CASK, IQGAP1, NPHS1, SPTAN1 and SPTBN1 (By similarity). Interacts with DDN (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a NGF-dependent manner (By similarity). Interacts with RAPGEF2; the interaction occurs before or after nerve growth factor (NGF) stimulation (By similarity). Interacts (via PDZ domain) with KIDINS220 (via C-terminal domain) (By similarity). Interacts with IGSF9 and HTR4 (PubMed:15466885, PubMed:15340156). Interacts with DLL1 (PubMed:15509766). Found in a complex with IGSF9B and NLGN2; the interaction with IGSF9B is mediated via the PDZ 5 and PDZ 6 domains, while the interaction with NLGN2 is mediated via the WW1, WW2 and PDZ2 domains (PubMed:23751499). Interacts (via PDZ 6 domain) with USH1G (via SAM domain); the interaction is triggered by phosphorylation of USH1G by CK2 and negatively regulates MAGI2-mediated endocytosis (PubMed:24608321).|||Late endosome|||Major.|||May be due to an intron retention.|||Membrane|||Photoreceptor inner segment|||Seems to act as a scaffold molecule at synaptic junctions by assembling neurotransmitter receptors and cell adhesion proteins (By similarity). Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth (By similarity). May play a role in regulating activin-mediated signaling in neuronal cells (PubMed:10681527). Enhances the ability of PTEN to suppress AKT1 activation (By similarity). Plays a role in receptor-mediated clathrin-dependent endocytosis which is required for ciliogenesis (PubMed:24608321).|||centriole|||centrosome|||cilium|||photoreceptor outer segment|||synaptosome http://togogenome.org/gene/10090:Pum2 ^@ http://purl.uniprot.org/uniprot/Q80U58 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic granule|||Homodimer; homodimerizes in vitro. Interacts with DAZ1, DAZL and NANOS1 via its pumilio repeats. Interacts with NANOS3 (By similarity). Interacts with SNAPIN. Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Interacts with DDX20. In case of viral infection, interacts with DHX58 (By similarity).|||Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Also mediates deadenylation-independent repression by promoting accessibility of miRNAs. Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation. Plays a role in cytoplasmic sensing of viral infection. Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm. May regulate DCUN1D3 mRNA levels. May support proliferation and self-renewal of stem cells. Binds specifically to miRNA MIR199A precursor, with PUM1, regulates miRNA MIR199A expression at a postranscriptional level (By similarity).|||The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface (PubMed:19540345). PUM2 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine (By similarity).|||Widely expressed. Expressed in embryonic stem cells, heart, kidney, lung, skin, intestine, spleen and thymus. Expressed at intermediate level in brain and liver. Weakly or not expressed in muscles and stomach. Expressed at various stages of myeloid and lymphoid cell development. In the testis expressed in the spermatogoni, spermatocytes, spermatids and Sertoli cells.|||perinuclear region http://togogenome.org/gene/10090:Smarcad1 ^@ http://purl.uniprot.org/uniprot/Q04692 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Binds to DNA preferentially in the vicinity of transcriptional start sites. Interacts with MSH2 and TRIM28. Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with PCNA (By similarity).|||Chromosome|||DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing (By similarity).|||Deficient mice have reduced viability and show growth retardation, skeletal dysplasia and impaired fertility.|||Detected at low levels in fertilized and unfertilized eggs. Levels increased in two-cell embryos, decreased up to morula stage and were highest in blastocysts. Highly expressed in the inner cell mass of 3.5 day old blastocysts. Highly expressed in ectoderm and visceral endoderm at day 5.5. Detected throughout the brain and spinal cord at day 10 to 15. Detected in the basal layer of the epidermis after day 12.5, in particular on snout and distal on fore- and hindlimbs.|||Nucleus http://togogenome.org/gene/10090:Tmem245 ^@ http://purl.uniprot.org/uniprot/D3YWD3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the autoinducer-2 exporter (AI-2E) (TC 2.A.86) family.|||Membrane http://togogenome.org/gene/10090:Mtx3 ^@ http://purl.uniprot.org/uniprot/D3YTP3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the metaxin family.|||Membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Mrps31 ^@ http://purl.uniprot.org/uniprot/Q61733 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS31 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Actn4 ^@ http://purl.uniprot.org/uniprot/P57780|||http://purl.uniprot.org/uniprot/Q3ULT2 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-actinin family.|||Cell junction|||Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.|||Cytoplasm|||Expressed in early elongating spermatids during spermiogenesis.|||F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (By similarity). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (PubMed:18332111). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (By similarity).|||Homodimer; antiparallel. Interacts with MAGI1 (By similarity). Interacts with PDLIM2 (By similarity). Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (By similarity). Binds TRIM3 at the N-terminus (By similarity). Interacts with MICALL2 (preferentially in opened conformation); stimulated by RAB13 activation (PubMed:18332111). Interacts with PPARG and RARA (By similarity). Binds to VCL; this interaction triggers VCL conformational changes (By similarity). Interacts with SEPTIN14 (PubMed:33228246).|||Nucleus|||perinuclear region|||stress fiber http://togogenome.org/gene/10090:Rab3c ^@ http://purl.uniprot.org/uniprot/P62823|||http://purl.uniprot.org/uniprot/Q542T7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Interacts with RIMS1, RIMS2, RPH3A and RPH3AL (PubMed:12578829). Interacts with GDI2, CHM and CHML; phosphorylation at Thr-86 disrupts these interactions (By similarity). Interacts with MADD (via uDENN domain); the GTP-bound form is preferred for interaction (PubMed:18849981).|||Phosphorylation of Thr-86 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitor GDI2.|||Protein transport. Probably involved in vesicular traffic (By similarity).|||Protein transport. Probably involved in vesicular traffic. http://togogenome.org/gene/10090:Snrpb2 ^@ http://purl.uniprot.org/uniprot/Q9CQI7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM U1 A/B'' family.|||Identified in the spliceosome B complex. Identified in the spliceosome C complex. Present in a spliceosome complex assembled in vitro, and composed of SNRPB2, HPRP8BP and CRNKL1. Contributes to the binding of stem loop IV of U2 snRNA with SNRPP1.|||Involved in pre-mRNA splicing as component of the spliceosome. Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA.|||Nucleus http://togogenome.org/gene/10090:Lsm14a ^@ http://purl.uniprot.org/uniprot/Q8K2F8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LSM14 family.|||Component of a ribonucleoprotein (RNP) complex (By similarity). Interacts with DDX6. Interacts with EIF4ENIF1/4E-T; promoting EIF4ENIF1/4E-T localization to P-bodies. Interacts (via FFD box) with EDC4 (By similarity).|||Essential for formation of P-bodies, cytoplasmic structures that provide storage sites for translationally inactive mRNAs and protect them from degradation. Acts as a repressor of mRNA translation. May play a role in mitotic spindle assembly.|||P-body|||Stress granule|||The LSM14 domain and the RGG repeats are required for accumulation in P-bodies, and the region containing the FDF motif is responsible for cytoplasmic retention.|||spindle http://togogenome.org/gene/10090:Cyp3a11 ^@ http://purl.uniprot.org/uniprot/Q3UEN8|||http://purl.uniprot.org/uniprot/Q64459 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||By dexamethasone.|||Catalyzes erythromycin N-demethylation, nifedipine oxidation and testosterone 6 beta-hydroxylation.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Highly expressed in liver.|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Ppp2r2b ^@ http://purl.uniprot.org/uniprot/Q6ZWR4 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aberrant splicing.|||Belongs to the phosphatase 2A regulatory subunit B family.|||Contains a cryptic mitochondrial transit peptide at positions 1-26.|||Cytoplasm|||Expressed in brain, testis, lung and spleen. In the brain, expressed in the cortex, hippocampus and cerebellum (at protein level).|||Expressed in embryo at 14 and 17 dpc.|||Membrane|||Mitochondrion|||Mitochondrion outer membrane|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with TOMM22 (By similarity). Interacts with IER5 (via N- and C-terminal regions) (By similarity).|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Within the PP2A holoenzyme complex, isoform 2 is required to promote proapoptotic activity. Isoform 2 regulates neuronal survival through the mitochondrial fission and fusion balance.|||The N-terminal 26 residues of isoform 2 constitute a cryptic mitochondrial matrix import signal with critical basic and hydrophobic residues, that is necessary and sufficient for targeting the PP2A holoenzyme to the outer mitochondrial membrane (OMM) and does not affect holoenzyme formation or catalytic activity.|||The last WD repeat of isoform 2 constitutes a mitochondrial stop-transfer domain that confers resistance to the unfolding step process required for import and therefore prevents PPP2R2B matrix translocation and signal sequence cleavage.|||cytoskeleton http://togogenome.org/gene/10090:Ghdc ^@ http://purl.uniprot.org/uniprot/Q99J23 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GH3 family.|||Endoplasmic reticulum|||Highly expressed in mammary tissues from mature virgins and at day 13 of pregnancy, and at lower level during lactation. Expressed at intermediate level in liver. Expressed at lower level in kidney, heart and brain.|||Nucleus envelope http://togogenome.org/gene/10090:Zfp647 ^@ http://purl.uniprot.org/uniprot/Q7TNU6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Tdpoz3 ^@ http://purl.uniprot.org/uniprot/Q717B4 ^@ Developmental Stage|||Similarity ^@ Belongs to the Tdpoz family.|||Strongly expressed in 2-cell embryos with weak expression detected in other embryonic stages. Also weakly expressed in adult testis. http://togogenome.org/gene/10090:Pusl1 ^@ http://purl.uniprot.org/uniprot/A2ADA5 ^@ Similarity ^@ Belongs to the tRNA pseudouridine synthase TruA family. http://togogenome.org/gene/10090:Gabra5 ^@ http://purl.uniprot.org/uniprot/Q8BHJ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA5 sub-subfamily.|||Cell membrane|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho (By similarity).|||Ligand-gated chloride channel subunit which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain. May be involved in GABA-A receptor assembly, and GABA-A receptor immobilization and accumulation by gephyrin at the synapse.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Hal ^@ http://purl.uniprot.org/uniprot/B2RXW1|||http://purl.uniprot.org/uniprot/P35492|||http://purl.uniprot.org/uniprot/Q8CE60 ^@ Disease Annotation|||PTM|||Similarity ^@ Belongs to the PAL/histidase family.|||Contains an active site 4-methylidene-imidazol-5-one (MIO), which is formed autocatalytically by cyclization and dehydration of residues Ala-Ser-Gly.|||Defects in Hal are the cause of histidinemia (His). http://togogenome.org/gene/10090:Rhox2b ^@ http://purl.uniprot.org/uniprot/A2A447 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ccn6 ^@ http://purl.uniprot.org/uniprot/D3Z5L9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CCN family.|||Deficient mice are viable and fertile with no obvious abnormalities in size, weight, skeletal development, ossification, or the occurrence of joint disease.|||Mitochondrion|||Plays a role in mitochondrial electron transport and mitochondrial respiration.|||Secreted http://togogenome.org/gene/10090:Gm4841 ^@ http://purl.uniprot.org/uniprot/E9QAA8 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Btd ^@ http://purl.uniprot.org/uniprot/A0A0R4J131|||http://purl.uniprot.org/uniprot/Q8CIF4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.|||Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.|||extracellular space http://togogenome.org/gene/10090:Adcy7 ^@ http://purl.uniprot.org/uniprot/P51829|||http://purl.uniprot.org/uniprot/Q3U1P1|||http://purl.uniprot.org/uniprot/Q3U1X9|||http://purl.uniprot.org/uniprot/Q3UU15 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by the G protein alpha subunit. Activated by the G protein beta and gamma subunit complex. Activated by GNA13 and GNA12. Ethanol and phorbol 12,13-dibutanoate significantly potentiate adenylate cyclase activity generated in response to the activation of the prostanoid receptor by the agonist prostaglandin E1(1-) in a PKC-dependent manner (By similarity). Inhibited by lithium (PubMed:18205980).|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of cAMP in response to activation of G protein-coupled receptors (Probable). Functions in signaling cascades activated namely by thrombin and sphingosine 1-phosphate and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G alpha protein with GNA13 (PubMed:18541530). Also, during inflammation, mediates zymosan-induced increase intracellular cAMP, leading to protein kinase A pathway activation in order to modulate innate immune responses through heterotrimeric G proteins G(12/13) (PubMed:23178822). Functions in signaling cascades activated namely by dopamine and C5 alpha chain and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G protein with G beta:gamma complex (By similarity). Functions, through cAMP response regulation, to keep inflammation under control during bacterial infection by sensing the presence of serum factors, such as the bioactive lysophospholipid (LPA) that regulate LPS-induced TNF-alpha production. However, it is also required for the optimal functions of B and T cells during adaptive immune responses by regulating cAMP synthesis in both B and T cells (PubMed:20505140).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.|||Knockout Adcy7 homozygous mice die during embryogenesis (more than 93%). To obtain adult animals with Adcy7-deficient immune systems, the hematopoietic stem cells obtained from the rare adult Adcy7 homozygous mice are transplanted into lethally irradiated wild-type animals. All chimeric mice survived the transplant procedure and appeared healthy. Adcy7-deficient mice appear to be hypersensitive to lipopolysaccharide-induced endotoxic shock and display a higher mortality rate.|||Membrane|||Most abundant in heart, spleen and lung.|||Phosphorylated by PRKCD.|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. http://togogenome.org/gene/10090:Abcg3 ^@ http://purl.uniprot.org/uniprot/Q99P81 ^@ Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.|||Highest levels of expression in thymus and spleen. Detected in lung and small intestine.|||May dimerize with another subunit to form a functional transporter.|||Membrane|||Seems to have a defective ATP-binding region. http://togogenome.org/gene/10090:Efna1 ^@ http://purl.uniprot.org/uniprot/D3YTT5|||http://purl.uniprot.org/uniprot/P52793|||http://purl.uniprot.org/uniprot/Q9D7K8 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Cell membrane|||Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Plays an important role in angiogenesis and tumor neovascularization. The recruitment of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Exerts anti-oncogenic effects in tumor cells through activation and down-regulation of EPHA2. Activates EPHA2 by inducing tyrosine phosphorylation which leads to its internalization and degradation. Acts as a negative regulator in the tumorigenesis of gliomas by down-regulating EPHA2 and FAK. Can evoke collapse of embryonic neuronal growth cone and regulates dendritic spine morphogenesis.|||Expressed in myogenic progenitor cells.|||In myogenic progenitor cells, expressed during the acquisition of muscle stem cell properties, from 18.5 dpc to adulthood.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Monomer. Homodimer. Forms heterodimers with EPHA2. Binds to the receptor tyrosine kinases EPHA2, EPHA3, EPHA4, EPHA5, EPHA6 and EPHA7. Also binds with low affinity to EPHA1 (By similarity).|||N-Glycosylation is required for binding to EPHA2 receptor and inducing its internalization.|||Secreted|||Undergoes proteolysis by a metalloprotease to give rise to a soluble monomeric form. http://togogenome.org/gene/10090:Smim3 ^@ http://purl.uniprot.org/uniprot/Q99PE5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or10p22 ^@ http://purl.uniprot.org/uniprot/Q14A42|||http://purl.uniprot.org/uniprot/Q60885 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Herc4 ^@ http://purl.uniprot.org/uniprot/Q6PAV2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Disruption causes defects in spermatozoon maturation and impaired fertility in males; females display normal fertility. Males produce litter sizes some 50% smaller, as well 50% of mature spermatozoa have reduced mobility.|||Highly expressed in testis during spermiogenesis. Expression was almost undetectable in testes at postnatal day 14 (P14). However, by P23, a strong increase in mRNA levels was observed with expression persisting to P40 when spermatozoa were first observed. Up-regulated in the uterine luminal epithelium at the time of embryo implantation.|||Probable E3 ubiquitin-protein ligase involved in either protein trafficking or in the distribution of cellular structures. Required for spermatozoon maturation and fertility, and for the removal of the cytoplasmic droplet of the spermatozoon. E3 ubiquitin-protein ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer it to targeted substrates.|||T.wilfordii induces abnormal expression of spermiogenesis genes including Herc4, the spermatogenic cells in the convoluted seminiferous tubules decrease and the lumen is obstructed by large deciduous spermatogenic cells. T.wilfordii has apparent antifertility effects.|||Ubiquitously expressed, highest expression is found in testis during spermiogenesis. It is specifically found in spermatogonia, spermatocytes, and spermatids with little or no expression detectable in the spermatozoa, or interstitial cells.|||cytosol http://togogenome.org/gene/10090:Vmn1r240 ^@ http://purl.uniprot.org/uniprot/D3YZG3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pygl ^@ http://purl.uniprot.org/uniprot/Q9ET01 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation, which is up-regulated by glucose and insulin and down-regulated by glucagon, inhibits the glycogen phosphorylase activity by promoting PPP1R3B-mediated recruitment of phosphatase PP1 and Ser-15 dephosphorylation.|||Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.|||Allosterically regulated through the non-covalent binding of metabolites, being activated by AMP and inhibited by ATP, ADP, and glucose-6-phosphate. The activity is also controlled by post-translational modifications including phosphorylation and acetylation.|||Belongs to the glycogen phosphorylase family.|||Homodimer; enzymatically active. Interacts with PPP1R3B; recruits the phosphatase PP1 which dephosphorylates and inactivates PYGL/glycogen phosphorylase.|||Phosphorylation at Ser-15 converts inactive phosphorylase b into active phosphorylase a. Dephosphorylation of Ser-15 by phosphatase PP1 inactivates the enzyme.|||cytosol http://togogenome.org/gene/10090:Gm13304 ^@ http://purl.uniprot.org/uniprot/P86792|||http://purl.uniprot.org/uniprot/P86793 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Binds to CCR7 and to CXCR3. Interacts with PDPN; relocalizes PDPN to the basolateral membrane.|||Expressed strongly in lung, spleen, thymus, peripheral and mesentric lymph nodes. Also expressed in the testis, kidney, liver, and heart.|||Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Potent mesangial cell chemoattractant. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs.|||Secreted|||Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c produce identical proteins while the protein produced by Ccl21a differs at only one position. Ccl21b and Ccl21c have Leu-65 (6Ckine-Leu) while Ccl21a has 'Ser-65' (6Ckine-Ser). http://togogenome.org/gene/10090:Stxbp4 ^@ http://purl.uniprot.org/uniprot/Q9WV89 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in skeletal muscle, heart, testis, adipocytes and pancreatic islet cells.|||Interacts with STX4A.|||Phosphorylated on Ser-99 by PKB/AKT2 after insulin treatment. Phosphorylation on Ser-99 abolishes the interaction with STX4A.|||Plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane. Inhibits the translocation of SLC2A4 from intracellular vesicles to the plasma membrane by STX4A binding and preventing the interaction between STX4A and VAMP2. Stimulation with insulin disrupts the interaction with STX4A, leading to increased levels of SLC2A4 at the plasma membrane. May also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose. http://togogenome.org/gene/10090:Or8s8 ^@ http://purl.uniprot.org/uniprot/Q8VET6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mov10 ^@ http://purl.uniprot.org/uniprot/E9PW39|||http://purl.uniprot.org/uniprot/P23249|||http://purl.uniprot.org/uniprot/Q3UD86 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 5' to 3' RNA helicase that is involved in a number of cellular roles ranging from mRNA metabolism and translation, modulation of viral infectivity, inhibition of retrotransposition, or regulation of synaptic transmission. Plays an important role in innate antiviral immunity by promoting type I interferon production. Mechanistically, specifically uses IKKepsilon/IKBKE as the mediator kinase for IRF3 activation. Contributes to UPF1 mRNA target degradation by translocation along 3' UTRs. Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC. In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2. Restricts retrotransposition of long interspersed element-1 (LINE-1) in cooperation with TUT4 and TUT7 counteracting the RNA chaperonne activity of L1RE1. Facilitates LINE-1 uridylation by TUT4 and TUT7 (By similarity). Required for embryonic viability and for normal central nervous system development and function. Plays two critical roles in early brain development: suppresses retroelements in the nucleus by directly inhibiting cDNA synthesis, while regulates cytoskeletal mRNAs to influence neurite outgrowth in the cytosol (PubMed:28662698). May function as a messenger ribonucleoprotein (mRNP) clearance factor (By similarity).|||As early as embryonic day 18, there is a higher level of expression in the whole brain compared to adults. Expression continues to rise at birth (P0) and remains elevated over adult levels until P10-P14, when it begins to decline (PubMed:28662698). Highly expressed throughout the P1 brain, including the cortex, hippocampus, cerebellum, midbrain, and hindbrain, there is very little expression in the adult brain except in the hippocampus (PubMed:28662698).|||Belongs to the DNA2/NAM7 helicase family. SDE3 subfamily.|||Cytoplasm|||Cytoplasmic ribonucleoprotein granule|||Interacts with DICER1, AGO2, TARBP2, EIF6 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with APOBEC3G in an RNA-dependent manner. Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:28662698) (By similarity). Interacts with both protein products of LIRE1, ORF1p and ORF2p (PubMed:28662698). Interacts with TUT4 and, to a lesser extent, TUT7; the interactions are RNA-dependent. Interacts with AGO2, TNRC6B and UPF1; the interactions are direct and RNA-dependent. Interacts with FMR1; this interaction is direct, occurs in an RNA-dependent manner on polysomes and induces association of MOV10 with RNAs (By similarity). Interacts with SHFL; the interaction increases in presence of RNA (By similarity). Interacts with DHX34; the interaction is RNA-independent (By similarity). Interacts with RBM46 (PubMed:36001654).|||Knockout leads to early embryonic lethality.|||Nucleus|||P-body|||Stress granule|||Ubiquitinated by the DCX(DCAF12) complex that specifically recognizes the glutamate-leucine (Glu-Leu) degron at the C-terminus, leading to its degradation. http://togogenome.org/gene/10090:Gabrb2 ^@ http://purl.uniprot.org/uniprot/P63137 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by benzodiazepines and the anesthetic etomidate (By similarity). Inhibited by the antagonist bicuculline (By similarity).|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB2 sub-subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Glycosylated.|||Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (By similarity). Interacts with UBQLN1 (By similarity). Interacts with KCTD8, KCTD12 and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents (PubMed:20400944). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).|||Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:20400944). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta2/gamma2 receptor and the alpha2/beta2/gamma2 receptor exhibit synaptogenic activity (PubMed:27129275). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).|||Postsynaptic cell membrane|||The extracellular domain contributes to synaptic contact formation. http://togogenome.org/gene/10090:Tamalin ^@ http://purl.uniprot.org/uniprot/Q9JJA9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Heteromer. Composed of TAMALIN, CYTH2 and at least one GRM1. Also interacts with GRM2, GRM3 and GRM5 (By similarity). Interacts with CYTH3 (PubMed:10828067).|||Highly expressed in brain, heart and lung, and to a lower extent in embryo, kidney and ovary.|||Plays a role in intracellular trafficking and contributes to the macromolecular organization of group 1 metabotropic glutamate receptors (mGluRs) at synapses.|||Postsynaptic cell membrane|||perinuclear region http://togogenome.org/gene/10090:Egfl8 ^@ http://purl.uniprot.org/uniprot/B9EJ41|||http://purl.uniprot.org/uniprot/Q6GUQ1 ^@ Caution|||Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Not detected before 11.5 dpc and expression levels vary between 11.5 dpc and 15.5 dpc.|||Secreted|||Ubiquitously expressed in brain, kidney, thymus and lung. http://togogenome.org/gene/10090:Gphn ^@ http://purl.uniprot.org/uniprot/A0JNY3|||http://purl.uniprot.org/uniprot/Q8BUV3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MoeA family.|||Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.|||Cell membrane|||Has also a catalytic activity and catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.|||Homotrimer, homodimer and homooligomer (PubMed:25025157). Interacts with SRGAP2 (via SH3 domain) (PubMed:22126966, PubMed:27373832). Interacts with GLRB (By similarity). Interacts with GABARAP (By similarity). Interacts with GABRA3 (By similarity). GABRA3 and GLRB occupy overlapping binding sites (By similarity). Interacts with ARHGAP32; IQSEC3, INSYN1 and INSYN2A (PubMed:27609886).|||In the C-terminal section; belongs to the MoeA family.|||In the N-terminal section; belongs to the MoaB/Mog family.|||Inhibited by copper and tungsten.|||Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Acts as a major instructive molecule at inhibitory synapses, where it also clusters GABA type A receptors (PubMed:25025157).|||Palmitoylated (PubMed:25025157). Palmitoylation is stimulated by GABA type A receptors activity (PubMed:25025157). Palmitoylation by ZDHHC12 regulates clustering at synapses (PubMed:25025157).|||Postsynaptic cell membrane|||Postsynaptic density|||cytoskeleton|||cytosol|||dendrite http://togogenome.org/gene/10090:Tlx3 ^@ http://purl.uniprot.org/uniprot/O55144 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Fev ^@ http://purl.uniprot.org/uniprot/E0CXR7|||http://purl.uniprot.org/uniprot/Q8QZW2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ETS family.|||Expressed in central serotonergic neurons.|||First expressed at 11 dpc in the rostral cluster of serotonergic neurons. During development, expression is restricted to serotonergic neurons located in the raphe nuclei.|||Functions as a transcriptional regulator. May function as a transcriptional repressor. Functions in the differentiation and the maintenance of the central serotonergic neurons. May play a role in cell growth.|||Mice display heightened aggressive and anxiety-like behaviors. They also display an extended and exacerbated period of breathing instability immediately after birth which results in an increased risk of death. This is associated with loss of the differentiation of a large number of the serotonin (5-HT) neurons without major structural abnormalities of the brain.|||Nucleus http://togogenome.org/gene/10090:Ascc2 ^@ http://purl.uniprot.org/uniprot/Q91WR3 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ASCC2 family.|||Identified in the ASCC complex that contains ASCC1, ASCC2 and ASCC3. Interacts directly with ASCC3. The ASCC complex interacts with ALKBH3. Interacts (via CUE domain) with 'Lys-63'-linked polyubiquitin chains, but not with 'Lys-48'-linked polyubiquitin chains. Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3. Component of the RQT (ribosome quality control trigger) complex, that contains ASCC2, ASCC3 and TRIP4. Interacts with CSRP1. Interacts with PRPF8, a component of the spliceosome. Interacts with ZCCHC4.|||Incomplete sequence.|||Nucleus|||Nucleus speckle|||The CUE domain specifically binds RPS20/uS10 ubiquitinated via 'Lys-63'-linked ubiquitin chains by ZNF598.|||Ubiquitin-binding protein involved in DNA repair and rescue of stalled ribosomes. Plays a role in DNA damage repair as component of the ASCC complex. Recruits ASCC3 and ALKBH3 to sites of DNA damage by binding to polyubiquitinated proteins that have 'Lys-63'-linked polyubiquitin chains. Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation. Involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation. Specifically recognizes and binds RPS20/uS10 ubiquitinated by ZNF598, promoting recruitment of the RQT (ribosome quality control trigger) complex on stalled ribosomes, followed by disassembly of stalled ribosomes. http://togogenome.org/gene/10090:Ankrd9 ^@ http://purl.uniprot.org/uniprot/Q8BH83 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle|||Part of an E3 ubiquitin-protein ligase complex with Elongin BC (ELOB and ELOC), CUL5 and ANKRD9. Interacts with IMPDH2; leading to ubiquitination of IMPDH2 and its subsequent proteasomal degradation.|||Substrate receptor subunit of a cullin-RING superfamily E3 ligase complex (CUL5-based E3 ubiquitin ligase complex) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Depending of the metabolic state of the cell, promotes the proteasomal degradation of IMPDH2, the rate-limiting enzyme in GTP biosynthesis or protects IMPDH2 by stabilizing IMPDH2 filaments assembly. Implicated in different cellular processes, like copper homeostasis and cell proliferation.|||cytosol http://togogenome.org/gene/10090:Mccc2 ^@ http://purl.uniprot.org/uniprot/B2RUK5|||http://purl.uniprot.org/uniprot/Q3ULD5|||http://purl.uniprot.org/uniprot/Q6PD20 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AccD/PCCB family.|||Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.|||Mitochondrion matrix|||Probably a dodecamer composed of six biotin-containing alpha subunits (MCCC1) and six beta (MCCC2) subunits. http://togogenome.org/gene/10090:Atg5 ^@ http://purl.uniprot.org/uniprot/Q99J83 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection.|||Acetylated by EP300.|||Belongs to the ATG5 family.|||Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane.|||Cytoplasm|||Forms a conjugate with ATG12 (PubMed:11266458, PubMed:12890687, PubMed:12665549, PubMed:18768753, PubMed:19417210). The ATG5-ATG12 conjugate forms a complex with several units of ATG16L1 (PubMed:12665549). Forms an 800-kDa complex composed of ATG12-ATG5 and ATG16L2 (PubMed:22082872). Interacts with TECPR1; the interaction is direct and does not take place when ATG16L1 is associated with the ATG5-ATG12 conjugate (By similarity). Interacts with DHX58/RIG-1, IFIH1/MDA5 and MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 conjugate form. The interaction with MAVS is further enhanced upon vesicular stomatitis virus (VSV) infection (PubMed:17709747). Interacts with ATG3 (By similarity). Interacts with ATG7 and ATG10 (PubMed:12482611). Interacts with FADD (By similarity). Interacts with Bassoon/BSN; this interaction is important for the regulation of presynaptic autophagy. Interacts with ATG16L2 (PubMed:22082872).|||Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.|||May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD (By similarity).|||Preautophagosomal structure membrane|||Ubiquitous. http://togogenome.org/gene/10090:Os9 ^@ http://purl.uniprot.org/uniprot/Q8K2C7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OS-9 family.|||Endoplasmic reticulum lumen|||Interacts (via C-terminus) with CPNE6 (via second C2 domain); this interaction occurs in a calcium-dependent manner in vitro (PubMed:10403379). Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1. FAM8A1 is stabilized by interaction with SYNV1, which prevents its proteasomal degradation. OS9 and UBE2J1 recruitment to the complex may be mediated by SEL1L (By similarity). Through this complex, may interact with ERLEC1 and HSPA5 (By similarity). Interacts with HSP90B1 (By similarity). Interacts with CREB3 (By similarity).|||Intramolecular disulfide bonds.|||Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4 (By similarity).|||N-glycosylated. http://togogenome.org/gene/10090:Rab10 ^@ http://purl.uniprot.org/uniprot/P61027 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Endosome membrane|||Expressed in the brain, specifically neurons (at protein level).|||Interacts with MYO5A; mediates the transport to the plasma membrane of SLC2A4/GLUT4 storage vesicles (PubMed:22908308). Interacts with GDI1; negatively regulates RAB10 association with membranes and activation (PubMed:19570034). Interacts (GDP-bound form) with LLGL1; the interaction is direct and promotes RAB10 association with membranes and activation through competition with the Rab inhibitor GDI1 (By similarity). Interacts with EXOC4; probably associates with the exocyst (By similarity). Interacts (GTP-bound form) with MICALCL, MICAL1, MICAL3, EHBP1 and EHBP1L1; at least in case of MICAL1 two molecules of RAB10 can bind to one molecule of MICAL1 (By similarity). Interacts with TBC1D13 (PubMed:22762500). Interacts with SEC16A (PubMed:27354378). Interacts with GDI2, CHM and CHML (By similarity). Interacts with LRRK2; interaction facilitates phosphorylation of Thr-73 (By similarity). Interacts with RILPL1 and RILPL2 when phosphorylated on Thr-73 (By similarity). Interacts with TBC1D21 (By similarity).|||Phosphorylation of Thr-73 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). That Rab is activated by the DENND4C guanine exchange factor (GEF) (Probable). That Rab is activated by the DENND4C and RABIF guanine exchange factors (GEF) (By similarity).|||Recycling endosome membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (By similarity). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane (By similarity). Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane (PubMed:17403373, PubMed:22908308, PubMed:27354378). In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response (PubMed:20643919). Also plays a specific role in asymmetric protein transport to the plasma membrane (By similarity). In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane (By similarity). In epithelial cells, it regulates transport from the Golgi to the basolateral membrane (By similarity). May play a role in the basolateral recycling pathway and in phagosome maturation (By similarity). May play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion (By similarity). Together with LRRK2, RAB8A, and RILPL1, it regulates ciliogenesis (By similarity). When phosphorylated by LRRK2 on Thr-73, it binds RILPL1 and inhibits ciliogenesis (By similarity).|||Up-regulated by LPS.|||cilium basal body|||perinuclear region|||phagosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Mapk1ip1 ^@ http://purl.uniprot.org/uniprot/Q9D7G9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MISS family.|||Cytoplasm|||Expressed in ovaries and immature oocytes and two cell stage embryos, then, it disappears. It is unstable during the first meiotic division and accumulates only during the second meiotic division.|||Interacts with MAPK1.|||Involved in the maintenance of the spindle integrity during the cytostatic factor (CSF) arrest of oocytes.|||Phosphorylated in vitro by MAPK1.|||spindle http://togogenome.org/gene/10090:Acot6 ^@ http://purl.uniprot.org/uniprot/B2RTE4|||http://purl.uniprot.org/uniprot/Q32Q92 ^@ Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. Catalyzes the hydrolysis of phytanoyl-CoA and pristanoyl-CoA, two methyl-branched fatty acids derived from phytol, that enter the body via the diet.|||Contaminating sequence. Small insertion of unknown origin.|||Highly expressed in white adipose tissue. Detected at lower levels in kidney, liver, brown adipose tissue and brain.|||Peroxisome|||Up-regulated in liver upon treatment with peroxisome proliferator. http://togogenome.org/gene/10090:Vmn1r112 ^@ http://purl.uniprot.org/uniprot/G3UY48 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd302 ^@ http://purl.uniprot.org/uniprot/Q9DCG2 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Potential multifunctional C-type lectin receptor that may play roles in endocytosis and phagocytosis as well as in cell adhesion and migration.|||cell cortex|||filopodium|||microvillus http://togogenome.org/gene/10090:Dock5 ^@ http://purl.uniprot.org/uniprot/B2RY04 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DOCK family.|||Cell membrane|||Cytoplasm|||Defects in Dock5 are the cause of rupture of lens cataract. It affects both eyes and is inherited as an autosomal recessive trait. Homozygotes spontaneously develop opacity of the lens at 35-60 days of age. The initial pathological changes appear at about 35 days of age in the deep layer of the posterior cortex as irregular swelling, condensation, degeneration and fragmentation of the lens fibers, leading to rupture of the lens capsule at the posterior pole at 45-100 days of age. Following rupture, the lens nucleus becomes dislocated behind the lens or occasionally in the anterior chamber.|||Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF proteins activate small GTPases by exchanging bound GDP for free GTP (PubMed:18396277). Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (By similarity).|||Highly expressed in lens, where it predominantly localizes to anterior epithelial cells, and is weakly expressed in lens fiber (at protein level). Expressed in brain, eye, lung, spleen and kidney, but not in thymus or peripheral blood leukocytes.|||In the lens, expressed from 15.5 dpc to maturity (PubMed:18396277). Expression increases during osteoclast differentiation (PubMed:27505886).|||Interacts with CRK and CRKL (By similarity). Interacts (via N-terminus) with tensin TNS3 (via N-terminus); the interaction increases DOCK5 guanine nucleotide exchange activity towards Rac (PubMed:27505886). Interacts with ELMO1 (PubMed:27505886).|||The DOCKER domain may mediate some GEF activity.|||podosome http://togogenome.org/gene/10090:Or4n5 ^@ http://purl.uniprot.org/uniprot/Q8VFC8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm11127 ^@ http://purl.uniprot.org/uniprot/A7VMS2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Or1x6 ^@ http://purl.uniprot.org/uniprot/A0A0N4SUP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nsd3 ^@ http://purl.uniprot.org/uniprot/Q6P2L6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.|||Chromosome|||Histone methyltransferase. Preferentially dimethylates 'Lys-4' and 'Lys-27' of histone H3 forming H3K2me2 and H3K27me2. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.|||Interacts with BRD4.|||Nucleus http://togogenome.org/gene/10090:Smu1 ^@ http://purl.uniprot.org/uniprot/Q3UKJ7 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 10.5 dpc expressed in otic vesicle.|||Belongs to the WD repeat SMU1 family.|||Component of the spliceosome B complex. Interacts with IK.|||Cytoplasm|||Involved in pre-mRNA splicing as a component of the spliceosome (By similarity). Regulates alternative splicing of the HSPG2 pre-mRNA (By similarity). Required for normal accumulation of IK (By similarity). Required for normal mitotic spindle assembly and normal progress through mitosis (By similarity).|||Nucleus|||Nucleus speckle|||The WD repeats assemble into a seven-bladed WD propeller. http://togogenome.org/gene/10090:Brinp1 ^@ http://purl.uniprot.org/uniprot/Q920P3 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BRINP family.|||Cytoplasm|||Expressed from 9.5 dpc.|||Expressed in brain (PubMed:15193423, PubMed:20025061, PubMed:29960053). Expressed in GABAergic neurons of the pre-frontal cortex (PubMed:29960053). Weakly expressed in embryonic stem (ES) cells and in ES-derived neural stem cells (NSCs) (PubMed:15193423, PubMed:20025061).|||Plays a role in neurogenesis, brain development, and the functioning of GABAergic neurons (PubMed:24528488, PubMed:27042284, PubMed:29960053). May suppress cell cycle progression in postmitotic neurons by inhibiting G1/S transition (PubMed:15193423, PubMed:24528488, PubMed:20025061).|||Up-regulated upon differentiation into neuronal cells in the presence of retinoic acid and BDNF. Up-regulated upon differentiation into astroglial cells. http://togogenome.org/gene/10090:Ank2 ^@ http://purl.uniprot.org/uniprot/Q8C8R3|||http://purl.uniprot.org/uniprot/S4R2R5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in eye lens fiber cells (at protein level) (PubMed:21745462). In the retina, expressed in the inner segments of rod photoreceptors (PubMed:19007774). Expressed in cardiomyocytes, as well as in skeletal muscles (PubMed:17940615, PubMed:27718357, PubMed:12571597). Also detected in brain and pancreas, as well as in kidney and spleen (at protein level) (PubMed:8253844, PubMed:17940615, PubMed:12571597). In the pancreas, highly expressed in islets, predominantly in beta cells, but low expression, if any in acinar cells (at protein level) (PubMed:17940615). In the central nervous system, expressed in the corpus callosum and in cerebellar Purkinje neurons (at protein level) (PubMed:17940615, PubMed:27718357). Expressed in lung and, at low levels, in testes (at protein level) (PubMed:17940615).|||Early endosome|||Expressed in neonatal developing ventricular cardiomyocytes as well as adult cardiomyocytes.|||Heterozygous knockout mice exhibit bradycardia and show a high degree of heart-rate variability associated with multiple episodes of abrupt sinus slowing and show episodes of intermittent isorhythmic atrioventricular dissociation similar to rhythm disturbances. Over half of the mutant animals die after exercise combined with epinephrine (PubMed:12571597). Mutant animals display premature senescence and reduced longevity (PubMed:17940615).|||Incomplete sequence.|||Interacts with RHBG (By similarity). Interacts with SPTBN1 (PubMed:15262991, PubMed:19007774). Colocalizes with Na/Ca exchanger (PubMed:19007774). Interacts with Na/K ATPases ATP1A1 and ATP1A2 (PubMed:19007774, PubMed:12571597). Directly interacts with DMD; this interaction is necessary for DMD localization at the sarcolemma. Interacts with DCTN4; this interaction is required for DCTN4 retention at costameres (PubMed:19109891). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (PubMed:21745462). Interacts (via death domain) with RABGAP1L (via Rab-GAP TBC domain) (PubMed:27718357). Interacts with SLC8A1/NCX1 (PubMed:12571597). May interact with inositol 1,4,5-trisphosphate receptors (PubMed:12571597).|||Lysosome|||M line|||Membrane|||Mitochondrion|||Phosphorylated at multiple sites by different protein kinases and each phosphorylation event regulates the protein's structure and function.|||Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions (PubMed:19109891). In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites (PubMed:12571597). Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:15262991). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (PubMed:19007774). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (PubMed:27718357).|||Postsynaptic cell membrane|||Recycling endosome|||T-tubule|||The tandem configuration of the two ZU5 and the UPA domains forms a structural supramodule termed ZZU. ZU5-1 mediates interaction with beta-spectrin, and the ZU5-1/UPA interface is required for ankyrin's function other than binding to spectrin (By similarity).|||Z line|||cytoskeleton http://togogenome.org/gene/10090:Klk1b8 ^@ http://purl.uniprot.org/uniprot/P07628 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Serpinb1c ^@ http://purl.uniprot.org/uniprot/Q5SV42 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Expressed in heart.|||Monomer. Interacts (via C-terminus) with CASP1 and CASP4 (via CARD domain); these interactions regulate the activity of inflammatory caspases.|||Regulates the activity of the neutrophil proteases. Forms only a stable complex with CTSG/Cathepsin G (By similarity). During inflammation, limits the activity of inflammatory caspases CASP1 and CASP4 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621). http://togogenome.org/gene/10090:Zfp207 ^@ http://purl.uniprot.org/uniprot/Q9JMD0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ In day-13 embryo, strongly expressed in the nervous system (brain, spinal cord and dorsal root ganglia), with strong to weak expression in other regions. Continues to be strongly expressed in the neonatal brain while expression is weak in the brain and spinal cord of adult.|||Interacts (via GLEBS region) with BUB3.|||Kinetochore- and microtubule-binding protein that plays a key role in spindle assembly. ZNF207/BuGZ is mainly composed of disordered low-complexity regions and undergoes phase transition or coacervation to form temperature-dependent liquid droplets. Coacervation promotes microtubule bundling and concentrates tubulin, promoting microtubule polymerization and assembly of spindle and spindle matrix by concentrating its building blocks (PubMed:26388440). Also acts as a regulator of mitotic chromosome alignment by mediating the stability and kinetochore loading of BUB3. Mechanisms by which BUB3 is protected are unclear: according to a first report, ZNF207/BuGZ may act by blocking ubiquitination and proteasomal degradation of BUB3. According to another report, the stabilization is independent of the proteasome (By similarity).|||Mainly composed of disordered low-complexity regions outside of the C2H2-type zinc fingers. Coacervation depends on hydrophobic and aromatic Phe and Tyr in the disordered low-complexity region, that may promote coacervation by forming intermolecular hydrophobic interactions.|||Nucleus|||The GLEBS region mediates interaction with BUB3.|||The microtubule-binding region is required for efficient loading of BUB3 onto kinetochores and proper mitosis.|||kinetochore|||spindle http://togogenome.org/gene/10090:Foxo3 ^@ http://purl.uniprot.org/uniprot/Q9WVH4 ^@ Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contaminating sequence. Potential poly-A sequence.|||Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation (By similarity). Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (PubMed:17521387). Deacetylated by SIRT3 (By similarity). Deacetylation by SIRT3 stimulates FOXO3-mediated mtDNA transcriptional activity in response to metabolic stress (By similarity).|||Expressed in white and brown adipose tissues (at protein level) (PubMed:22510882). Expressed in liver, kidney, lung and colon (at protein level) (PubMed:29445193). Expressed in skeletal muscles (at protein level) (PubMed:23283301).|||Heavily methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-270. Methylation doesn't affect subcellular location.|||In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-252 by AKT1/PKB (Probable). This phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm (Probable). Survival factor withdrawal induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces transcription of target genes and triggers apoptosis (By similarity). Although AKT1/PKB doesn't appear to phosphorylate Ser-314 directly, it may activate other kinases that trigger phosphorylation at this residue (By similarity). Phosphorylated by STK4/MST1 on Ser-208 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation (By similarity). Phosphorylated by PIM1 (By similarity). Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting subcellular localization (By similarity). Phosphorylated by AMPK on Ser-30 in response to metabolic stress which mediates FOXO3 mitochondrial translocation (By similarity). Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (By similarity). Phosphorylated by CHUK/IKKA and IKBKB/IKKB (By similarity). TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-643 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (By similarity). May be dephosphorylated by calcineurin A on Ser-298 which abolishes FOXO3 transcriptional activity (PubMed:23805378). Phosphorylation at Ser-252 promotes its degradation by the proteasome (By similarity). Dephosphorylation at Ser-252 by protein phosphatase 2A (PPP2CA) promotes its stabilization; interaction with PPP2CA is enhanced by AMBRA1 (By similarity).|||Mitochondrion matrix|||Mitochondrion outer membrane|||Nucleus|||Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation.|||The N-terminus is cleaved following import into the mitochondrion.|||Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:18054316, PubMed:18054315, PubMed:23805378). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (PubMed:18054316, PubMed:18054315, PubMed:25402684). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (By similarity). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (By similarity). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (PubMed:32103177). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (By similarity).|||Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (By similarity). Interacts with SIRT2; the interaction occurs independently of SIRT2 deacetylase activity (PubMed:17521387). Interacts with YWHAB/14-3-3-beta and YWHAZ/14-3-3-zeta, which are required for cytosolic sequestration. Upon oxidative stress, interacts with STK4/MST1, which disrupts interaction with YWHAB/14-3-3-beta and leads to nuclear translocation. Interacts with PIM1. Interacts with DDIT3/CHOP. Interacts (deacetylated form) with SKP2. Interacts with CHUK and IKBKB (By similarity). Interacts with CAMK2A, CAMK2B and calcineurin A (PubMed:23805378). Interacts with NUPR1; this interaction represses FOXO3 transactivation (By similarity).|||cytosol http://togogenome.org/gene/10090:Vmn2r35 ^@ http://purl.uniprot.org/uniprot/E9Q7U8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mgst1 ^@ http://purl.uniprot.org/uniprot/E9QJW0|||http://purl.uniprot.org/uniprot/Q53ZD4|||http://purl.uniprot.org/uniprot/Q91VS7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-42 and Lys-55 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the MAPEG family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Endoplasmic reticulum membrane|||Expressed in the testes (at protein level).|||Homotrimer; The trimer binds only one molecule of glutathione.|||Membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Tmem179b ^@ http://purl.uniprot.org/uniprot/Q9CY24 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM179 family.|||Membrane http://togogenome.org/gene/10090:Mpzl1 ^@ http://purl.uniprot.org/uniprot/Q3TEW6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the myelin P0 protein family.|||Cell surface receptor, which is involved in signal transduction processes. Recruits PTPN11/SHP-2 to the cell membrane and is a putative substrate of PTPN11/SHP-2. Is a major receptor for concanavalin-A (ConA) and is involved in cellular signaling induced by ConA, which probably includes Src family tyrosine-protein kinases. Isoform 2 seems to have a dominant negative role; it blocks tyrosine phosphorylation of MPZL1 induced by ConA. Isoform 1, but not isoform 2, may be involved in regulation of integrin-mediated cell motility (By similarity).|||Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Interacts with phosphorylated PTPN11/SHP-2.|||Membrane|||Phosphorylated on tyrosine residues upon stimulation with pervanadate and concanavalin-A (ConA). Phosphorylation at Tyr-242 and Tyr-264 is required for interaction with PTPN11/SHP-2. Dephosphorylated by PTPN11/SHP-2 (in vitro) (By similarity). http://togogenome.org/gene/10090:Tmem109 ^@ http://purl.uniprot.org/uniprot/Q3UBX0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Functions as a voltage-gated monoatomic cation channel permeable to both potassium and calcium (By similarity). Plays a role in the cellular response to DNA damage (PubMed:20060811).|||Homooligomer. Interacts with CRYAB; in the cellular response to DNA damage.|||Nucleus outer membrane|||Sarcoplasmic reticulum membrane|||Viable and normal in appearance. http://togogenome.org/gene/10090:Or5v1b ^@ http://purl.uniprot.org/uniprot/Q7TRK1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4c12b ^@ http://purl.uniprot.org/uniprot/A2AUA4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nsun5 ^@ http://purl.uniprot.org/uniprot/Q8K4F6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.|||Decreased body weight and lean mass without alterations in food intake (PubMed:31722427). Adult mice show spatial cognitive deficits, possibly caused by defects in development and function of oligodendrocyte precursor cells (PubMed:30485550). Mice display a reduction of the corpus callosum with a decline in the number of myelinated axons and loose myelin sheath (PubMed:31174389). They also show impaired development of the cerebral cortex, characterized by impaired growth of radial glial scaffold (PubMed:31462248).|||In the hippocampus, specifically expressed in adult hippocampal NG2-positive oligodendrocyte precursor cells (at protein level).|||Present in the developing cerebral cortex from embryonic day 12.5 dpc, with a peak at 14.5 dpc followed by a decrease from 18.5 dpc (at protein level) (PubMed:31462248). Selectively expressed in radial glial cells of cerebral cortex from 12.5 to 16.5 dpc, but not in intermediate progenitor cells (IPCs) or neocortical neurons (at protein level) (PubMed:31462248). Highly expressed in callosal oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) from postnatal day 7 to postnatal day 28 (PubMed:31174389).|||S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 3438 (m5C3438) in 28S rRNA (PubMed:31722427). m5C3782 promotes protein translation without affecting ribosome biogenesis and fidelity (By similarity). Required for corpus callosum and cerebral cortex development (PubMed:31174389, PubMed:31462248).|||nucleolus http://togogenome.org/gene/10090:Mdh1b ^@ http://purl.uniprot.org/uniprot/Q5F204 ^@ Similarity ^@ Belongs to the LDH/MDH superfamily. MDH type 2 family. http://togogenome.org/gene/10090:Dnph1 ^@ http://purl.uniprot.org/uniprot/Q80VJ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2'-deoxynucleoside 5'-phosphate N-hydrolase 1 family.|||Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.|||Cytoplasm|||Monomer and homodimer.|||Nucleus http://togogenome.org/gene/10090:Hkdc1 ^@ http://purl.uniprot.org/uniprot/Q91W97 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the hexokinase family.|||Catalyzes the phosphorylation of hexose to hexose 6-phosphate, although at very low level compared to other hexokinases (By similarity). Has low glucose phosphorylating activity compared to other hexokinases (By similarity). Involved in glucose homeostasis and hepatic lipid accumulation (PubMed:30543855). Required to maintain whole-body glucose homeostasis during pregnancy; however additional evidences are required to confirm this role (PubMed:25648650, PubMed:27459389).|||Cytoplasm|||Embryonic lethality.|||Mitochondrion membrane|||Photoreceptor inner segment|||Widely expressed. Detected in retina, brain, cerebellum, liver, lung, kidney, spleen, pancreas and intestine (PubMed:30085091). http://togogenome.org/gene/10090:Pttg1ip2 ^@ http://purl.uniprot.org/uniprot/D3YUK8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ocstamp ^@ http://purl.uniprot.org/uniprot/Q9D611 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in osteoclast (at protein level). Ubiquitous. Highly expressed in multi-nuclear osteoclast cells compared to mono-nuclear macrophages. Expressed in foreign body giant cells (FBGCs).|||Membrane|||Mice show a lack of multi-nuclear osteoclast and foreign body giant cell formation and a bone-resorbing efficiency reduction.|||Probable cell surface receptor that plays a role in cellular fusion and cell differentiation. Cooperates with DCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign body giant cells (FBGCs). Involved in osteoclast bone resorption. Promotes osteoclast differentiation and may play a role in the multinucleated osteoclast maturation.|||Up-regulated during osteoclast and foreign body giant cells (FBGCs) differentiation by TNFSF11 and cytokines. Down-regulated by estrogen. http://togogenome.org/gene/10090:Krtdap ^@ http://purl.uniprot.org/uniprot/Q3V2T4 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression restricted to suprabasal keratinocytes of the epidermis.|||May act as a soluble regulator of keratinocyte differentiation. May play an important role in embryonic skin morphogenesis (By similarity).|||Secreted http://togogenome.org/gene/10090:Aldh8a1 ^@ http://purl.uniprot.org/uniprot/Q8BH00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Catalyzes the NAD-dependent oxidation of 2-aminomuconic semialdehyde of the kynurenine metabolic pathway in L-tryptophan degradation.|||Cytoplasm|||Detected in hepatocytes and in proximal and distal convoluted tubules in kidney cortex (at protein level). Highly expressed in adult liver and in kidney cortex. First detected in embryonic liver after 15 days of development. http://togogenome.org/gene/10090:Or5j1 ^@ http://purl.uniprot.org/uniprot/Q7TR57 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bbs4 ^@ http://purl.uniprot.org/uniprot/Q8C1Z7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BBS4 family.|||Cytoplasm|||Expressed in the hippocampus and dentate gyrus, the columnar epithelial cells of bronchioles, the olfactory epithelium and the inner segment and outer nuclear layer of the retina. Expressed in testis.|||Expressed in the pericardium of the developing embryo and in the epidermal layer surrounding the digits.|||Males are sterile due to a loss of sperm flagella. In mice obesity is associated with hyperleptinemia and resistance to the anorectic and weight-reducing effects of leptin. Although mice are resistant to the metabolic actions of leptin, animals remain responsive to the effects of leptin on renal sympathetic nerve activity and arterial pressure and developed hypertension. BBS mice have decreased hypothalamic expression of proopiomelanocortin (POMC). BBS genes play an important role in maintaining leptin sensitivity in POMC neurons.|||Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1 and DCTN1. Interacts with DC28B. Interacts with ALDOB and C2CD3. Interacts with PKD1 (By similarity). Interacts with CEP290 (By similarity). Interacts with DLEC1 (By similarity).|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization. Required for microtubule anchoring at the centrosome but not for microtubule nucleation. May be required for the dynein-mediated transport of pericentriolar proteins to the centrosome (By similarity).|||centriolar satellite|||centrosome|||cilium|||cilium membrane|||flagellum http://togogenome.org/gene/10090:Poc1a ^@ http://purl.uniprot.org/uniprot/Q8JZX3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat POC1 family.|||Interacts with POC1B.|||Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1B to ensure centriole integrity and proper mitotic spindle formation (By similarity).|||Widely expressed in embryonic and adult tissues.|||centriole|||cilium basal body|||spindle pole http://togogenome.org/gene/10090:Vmn2r86 ^@ http://purl.uniprot.org/uniprot/G5E8Y4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Clcnkb ^@ http://purl.uniprot.org/uniprot/Q9WUB6 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family. CLCNKB subfamily.|||Cell membrane|||Due to intron retention.|||Interacts with BSND. Forms heteromers with BSND in the thick ascending limb of Henle and more distal segments.|||Specifically expressed in the kidney. All nephron segments expressing BSND also express CLCNK proreins.|||Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume; membrane potential stabilization, signal transduction and transepithelial transport. May be important in urinary concentrating mechanisms. May be the basolateral chloride channel mediating net chloride absorption in CTAL cells. http://togogenome.org/gene/10090:Chrdl1 ^@ http://purl.uniprot.org/uniprot/Q920C1 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in heart, brain, lung, liver, kidney and testis.|||Expression starts in the neural plate at mid-gastrulation. Later on its expression becomes restricted to discrete regions of the central nervous system and to derivatives of the neural crest cells. Expressed as well in the primordial cells of the skeleton in mice embryos at 13.5 dpc.|||May be glycosylated.|||Secreted|||Seems to antagonize the function of BMP4 by binding to it and preventing its interaction with receptors. Alters the fate commitment of neural stem cells from gliogenesis to neurogenesis. Contributes to neuronal differentiation of neural stem cells in the brain by preventing the adoption of a glial fate. May play a crucial role in dorsoventral axis formation (By similarity). Antagonizes the function of BMP7 and may thus play an important role in the embryonic bone formation. Shows no inhibitory effect on the inducing activity of BMP2. Plays a role during anterior segment eye development (By similarity). http://togogenome.org/gene/10090:Apoa2 ^@ http://purl.uniprot.org/uniprot/P09813 ^@ Disease Annotation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the apolipoprotein A2 family.|||Defects in Apoa2 are the cause of senescence accelerated mouse (SAM), the senile amyloid is a mutated apolipoprotein A-II.|||May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism.|||Monomer. Interacts with NAXE and NDRG1 (By similarity).|||Plasma.|||Secreted|||The apo A-II stoichiometry in HDL molecules varies among inbred mice strains, because of structural polymorphisms affecting the apo A-II gene, which influence its translational efficiency.|||The sequence presented here is that of strain BALB/c and C3H/HeJ. http://togogenome.org/gene/10090:H3f4 ^@ http://purl.uniprot.org/uniprot/A0A8I4SYN6 ^@ Similarity|||Subunit ^@ Belongs to the histone H3 family.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Sdhd ^@ http://purl.uniprot.org/uniprot/Q9CXV1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CybS family.|||Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.|||Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:2310061N02Rik ^@ http://purl.uniprot.org/uniprot/Q9D6S9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Neil1 ^@ http://purl.uniprot.org/uniprot/Q8K4Q6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FPG family.|||Chromosome|||Detected in heart, spleen and lung.|||Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches. Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.|||Nucleus|||Up-regulated during S-phase.|||centrosome http://togogenome.org/gene/10090:Or10a2 ^@ http://purl.uniprot.org/uniprot/Q7TRN0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tex33 ^@ http://purl.uniprot.org/uniprot/Q9D9J2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Initially expressed in the cytoplasm of round spermatids, expression diminishes in elongated spermatid (PubMed:28742876). Detected in testis at 28 days after birth and expression is maintained (PubMed:28742876, PubMed:33760102).|||Mutant adult male are fertile and there is no significant change on litter size compared with male wild-type adult. No differences are found in testis/body weight ratios, testicular/epididymal tissue morphology, sperm counts, sperm morphology and spermatozoa motility.|||Only detected in testis, in the spermatids and sperm within the seminiferous tubules (at protein level).|||Seems to be associated with spermiogenesis but is not essential for sperm development and male fertility.|||acrosome|||flagellum http://togogenome.org/gene/10090:Gm20818 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Sytl5 ^@ http://purl.uniprot.org/uniprot/Q80T23 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds RAB27A that has been activated by GTP-binding.|||May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids (By similarity).|||Membrane http://togogenome.org/gene/10090:2810408A11Rik ^@ http://purl.uniprot.org/uniprot/B1AR39|||http://purl.uniprot.org/uniprot/B1AR42|||http://purl.uniprot.org/uniprot/Q6NSU2 ^@ Similarity ^@ Belongs to the protein phosphatase inhibitor 2 family. http://togogenome.org/gene/10090:Flrt3 ^@ http://purl.uniprot.org/uniprot/Q8BGT1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in adult brain (PubMed:21350012). Detected in embryonic rostral thalamus neurons (at protein level) (PubMed:24560577). Detected in embryonic rostral thalamus neurons (PubMed:24560577). Detected in neonate eye, in the inner plexiform layer and the outer nuclear layer (PubMed:25374360).|||Detected in embryonic brain at 13 dpc. Levels in brain decrease gradually after 15 dpc, but expression continues after birth (PubMed:21673655). Detected in embryonic myocardium, body wall and pro-epicardial organ at 9.5 dpc. Detected throughout the myocardium at 10.5 dpc, but levels in the epicardial cell layer are strongly decreased. Almost exclusively detected in the neural tube at 14.5 dpc (at protein level) (PubMed:21350012). Detected in the chorion and visceral endoderm between 6 and 8 dpc (PubMed:19056886). Detected in the visceral endoderm at 7 dpc, with a gradient from high expression in the anterior part to low expression at the posterior part (PubMed:19056886). At 8 dpc, detected in definitve endoderm, parts of the neuroectoderm, the headfold and posterior mesoderm (PubMed:19056886). Detected in the developing brain, the proepicardial organ and in somites at 8.5 dpc (PubMed:16872596, PubMed:18448090). At 9.5 and 10.5 dpc, detected in telencephalic vesicles, at the midbrain boundaries with forebrain and hindbrain, the hypothalamic region, in the apical ectodermal ridge, pharyngeal arches, the developing eye, the epithelial structures surrounding the lower region of the developing heart, limb buds and somites (PubMed:16872596, PubMed:18448090). At 10.5 dpc, detected at interlimb somites with loss of expression at limb somites and anterior trunk somites. At 11 dpc, detected in mesoderm in head and branchial arches, migrating germ cells and limbs (PubMed:16872596).|||Endoplasmic reticulum membrane|||Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners (PubMed:19056886, PubMed:25374360). Plays a role in the spatial organization of brain neurons (PubMed:25374360). Plays a role in vascular development in the retina (PubMed:25374360). Plays a role in cell-cell adhesion via its interaction with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25374360). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5B, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25374360). Promotes neurite outgrowth (in vitro) (By similarity). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length (By similarity). Plays a role in the regulation of the density of glutamaergic synapses (PubMed:22405201). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning (PubMed:19056886). Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development (PubMed:18448090). Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (PubMed:19056886).|||Heterozygous mice are viable and fertile, but homozygous mice display nearly complete embryonic lethality. Most embryos die at about 10.5 dpc (PubMed:18448090, PubMed:19056886). A majority present disruption of the basement membrane and ruptures of the anterior visceral endoderm (PubMed:19056886). About one third display a pronounced defect in the fusion of the lateral edges of the body wall, resulting in cardia bifida. Mutant mice display also a defect in proepicardial cell migration. About one third of the mutants display abnormal morphogenesis of the neuroepithelium and headfold fusion defects. Besides, mutant embryos display defects in definitive endoderm migration, resulting in anterior axis truncations. Each of these phenotypes has partial penetrance, and many mutant embryos present a spectrum of defects. About 3% of the mutants develop into viable and fertile adults (PubMed:18448090, PubMed:19056886).|||Monomer and homodimer (By similarity). Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:25374360). Interacts with FGFR1 (PubMed:16872596). Interacts (via extracellular domain) with ADGRL1/LPHN1 and LPHN2 (via olfactomedin-like domain) (PubMed:22405201). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain) (PubMed:24739570, PubMed:22405201, PubMed:26235031). Interacts (via extracellular domain) with UNC5B (via Ig domain) (PubMed:19492039, PubMed:21673655, PubMed:22405201, PubMed:25374360). May also interact (via extracellular domain) with UNC5A and UNC5C (PubMed:22405201). Interacts (via extracellular domain) with UNC5D (via extracellular domain) (PubMed:19492039). Identified in complexes composed of FLRT3, ADGRL3 and UNC5B, respectively FLRT3, ADGRL3 and UNC5D (By similarity). Interacts (via cytoplasmic domain) with ROBO1 (PubMed:24560577).|||N-glycosylated.|||Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.|||Secreted|||Up-regulated by FGF2.|||axon|||focal adhesion|||growth cone membrane http://togogenome.org/gene/10090:Zc3h15 ^@ http://purl.uniprot.org/uniprot/Q3TIV5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZC3H15/TMA46 family.|||By erythropoietin.|||Cytoplasm|||Interacts with DRG1; the interaction forms a polysomal DRG1-DFRP1/ZC3H15 complex which provides protein stability to DRG1 possibly by blocking poly-ubiquitination (PubMed:15676025). Associates with microtubules (By similarity).|||Nucleus|||Protects DRG1 from proteolytic degradation (PubMed:15676025). Stimulates DRG1 GTPase activity likely by increasing the affinity for the potassium ions (By similarity). http://togogenome.org/gene/10090:Sod3 ^@ http://purl.uniprot.org/uniprot/O09164|||http://purl.uniprot.org/uniprot/Q542X9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Cu-Zn superoxide dismutase family.|||Binds 1 copper ion per subunit.|||Binds 1 zinc ion per subunit.|||Destroys radicals which are normally produced within the cells and which are toxic to biological systems.|||Homotetramer (By similarity). Directly interacts with ATP7A/MNK; this interaction is copper-dependent and is required for SOD3 activity (By similarity).|||Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen.|||extracellular space|||trans-Golgi network http://togogenome.org/gene/10090:Epgn ^@ http://purl.uniprot.org/uniprot/Q0VEB7|||http://purl.uniprot.org/uniprot/Q924X1 ^@ Caution|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at low levels in testis, heart and liver.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Promotes the growth of epithelial cells. May stimulate the phosphorylation of EGFR and mitogen-activated protein kinases. http://togogenome.org/gene/10090:Usp27x ^@ http://purl.uniprot.org/uniprot/Q8CEG8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although strongly related to USP22, which deubiquitinates histones, lacks the N-terminal UBP-type zinc finger, suggesting it does not have the ability to deubiquitinate histones.|||Belongs to the peptidase C19 family.|||Deubiquitinase involved in innate antiviral immunity by mediating deubiquitination of CGAS and RIGI (PubMed:31534008). Negatively regulates RIGI by mediating 'Lys-63'-linked deubiquitination of RIGI, inhibiting type I interferon signaling (By similarity). Also regulates 'Lys-63'-linked ubiquitination level of MDA5/IFIH1 (By similarity). Acts as a positive regulator of the cGAS-STING pathway by catalyzing 'Lys-48'-linked deubiquitination of CGAS, thereby promoting its stabilization (PubMed:31534008). Can reduce the levels of BCL2L11/BIM ubiquitination and stabilize BCL2L11 in response to the RAF-MAPK-degradation signal (PubMed:27013495). By acting on BCL2L11 levels, may counteract the anti-apoptotic effects of MAPK activity (PubMed:27013495).|||Interacts with phosphorylated BCL2L11 isoform BIMEL; this interaction leads to BCL2L11 deubiquitination and stabilization.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Atp6v0b ^@ http://purl.uniprot.org/uniprot/Q3U889|||http://purl.uniprot.org/uniprot/Q91V37 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase proteolipid subunit family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Proton-conducting pore forming of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.|||Proton-conducting pore forming subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).|||Ubiquitous.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with IFITM3 (PubMed:22467717).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Mydgf ^@ http://purl.uniprot.org/uniprot/Q9CPT4 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MYDGF family.|||Bone marrow-derived monocyte and paracrine-acting protein that promotes cardiac myocyte survival and adaptive angiogenesis for cardiac protection and/or repair after myocardial infarction (MI). Stimulates endothelial cell proliferation through a MAPK1/3-, STAT3- and CCND1-mediated signaling pathway. Inhibits cardiac myocyte apoptosis in a PI3K/AKT-dependent signaling pathway.|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Expressed in prostate, spleen and lung, and weakly expressed in the left ventricle (LF) and liver. Expressed predominantly in inflammatory cells, such as monocytes and macrophages, and weakly expressed in neutrophils, T-cells, B-cells, endothelial cells and cardiac myocytes, after myocardial infarction (MI) (at protein level).|||Golgi apparatus|||It has been reported that MYDGF is secreted into blood plasma (PubMed:15378209, PubMed:25581518). However, another report studying human MYDGF shows resident localization to the endoplasmic reticulum and Golgi apparatus and secretion when the two most C-terminal residues of the RTEL motif are abolished (By similarity).|||Mice show normal postnatal body mass gain, develop normally and are fertile. Show larger infarct collagen-rich scars and more severe heart contractile dysfunction compared to wild-type mice after ischemia and reperfusion (IR) injury.|||Secreted|||Up-regulated by ischemia/hypoxia and reperfusion (IR) injury in the left ventricle (at protein level) (PubMed:25581518). Up-regulated during adipocyte differentiation (at protein level) (PubMed:15378209).|||Was originally thought to signal lymphoid cells to proliferate via thymic shared antigen 1 (PubMed:11714798). This work was later retracted (PubMed:12538725). http://togogenome.org/gene/10090:Gm21518 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Ankfy1 ^@ http://purl.uniprot.org/uniprot/Q810B6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic vesicle|||Endosome membrane|||Expressed in kidney proximal tubule epithelial cells; at protein level.|||Interacts with RAB5A (in GTP-bound form). Interacts with RHOD (independent of GTP-loaded status). Interacts with EHD1. Interacts with VPS26A; the interaction is independent of EHD1 and is indicative for an association with the cargo recognition subcomplex of the retromer complex.|||Proposed effector of Rab5. Binds to phosphatidylinositol 3-phosphate (PI(3)P). Involved in homotypic early endosome fusion and to a lesser extent in heterotypic fusion of chlathrin-coated vesicles with early endosomes. Required for correct endosomal localization. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Regulates the subcellular localization of the retromer complex in a EHD1-dependent manner. Involved in endosome-to-Golgi transport and biosynthetic transport to late endosomes and lysosomes indicative for a regulation of retromer complex-mediated retrograde transport (By similarity). Involved in macropinocytosis; the function is dependent on Rab5-GTP. http://togogenome.org/gene/10090:Pxmp4 ^@ http://purl.uniprot.org/uniprot/Q9JJW0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxisomal membrane protein PXMP2/4 family.|||Interacts with PEX19.|||Peroxisome membrane http://togogenome.org/gene/10090:Vmn1r80 ^@ http://purl.uniprot.org/uniprot/L7N1Z3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc22a12 ^@ http://purl.uniprot.org/uniprot/Q8CFZ5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Detected in kidney (at protein level). Detected in kidney cortex, in proximal tubules.|||Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions (PubMed:14747372). Involved in renal reabsorption of urate and helps maintaining blood levels of uric acid (PubMed:14747372). Mediates urate uptake by an exchange with organic anions such as (S)-lactate and nicotinate, and inorganic anion Cl(-) (PubMed:14747372). Other inorganic anions such as Br(-), I(-) and NO3(-) may also act as counteranions that exchange for urate (By similarity). Also mediates orotate tubular uptake coupled with nicotinate efflux and to a lesser extent with lactate efflux, therefore displaying a potential role in orotate renal reabsorption. Orotate transport is Cl(-)-dependent (By similarity).|||Interacts with PDZK1.|||N-glycosylated. http://togogenome.org/gene/10090:Sgip1 ^@ http://purl.uniprot.org/uniprot/Q8VD37 ^@ Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in brain, spinal cord and cerebellum.|||Interacts with proteins essential or regulating the formation of functional clathrin-coated pits (Probable). Interacts with CANX (PubMed:17626015, PubMed:21747946). Interacts with AP2A1 (PubMed:17626015). Interacts with EPS15 (PubMed:17626015). Interacts with SH3GL3 (By similarity). Interacts with AMPH (By similarity). Interacts with ITSN1 (via SH3 domains) (By similarity). Interacts with and REPS1 (By similarity).|||May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis.|||The N-terminal domain (1-97) of this isoform mediates binding to and tubulation of membranes.|||Up-regulated in the hypothalamus of obese mice.|||clathrin-coated pit http://togogenome.org/gene/10090:Atad2 ^@ http://purl.uniprot.org/uniprot/G3X963|||http://purl.uniprot.org/uniprot/Q6IQY4|||http://purl.uniprot.org/uniprot/Q8CDM1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Interacts with ESR1 and NCOA3 and these interactions are enhanced by estradiol. Interacts with acetylated lysine residues on histone H1.4, H2A, H2B and H3 (in vitro) (By similarity).|||May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation (By similarity).|||Nucleus http://togogenome.org/gene/10090:Folr1 ^@ http://purl.uniprot.org/uniprot/P35846 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the folate receptor family.|||Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:1894617). Has high affinity for folate and folic acid analogs at neutral pH (By similarity). Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release (By similarity). Required for normal embryonic development and normal cell proliferation (PubMed:10508523, PubMed:12854656, PubMed:15259034, PubMed:17286298). Required for renal folate reabsorption (PubMed:15703271).|||Cell membrane|||Cytoplasmic vesicle|||Detected in kidney proximal tubules (at protein level).|||Embryonic lethality at about 10.5 dpc, due to gross developmental defects, including defects of neural tube closure, craniofacial defects and defects in heart development. Embryos can be rescued by maternal folate supplementation.|||Endosome|||Secreted|||The secreted form is derived from the membrane-bound form either by cleavage of the GPI anchor, or/and by proteolysis catalyzed by a metalloprotease.|||clathrin-coated vesicle http://togogenome.org/gene/10090:Ccl2 ^@ http://purl.uniprot.org/uniprot/P10148|||http://purl.uniprot.org/uniprot/Q5SVU3 ^@ Function|||Induction|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (By similarity). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (PubMed:29993042). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (PubMed:29993042).|||Belongs to the intercrine beta (chemokine CC) family.|||By platelet-derived growth factor (PubMed:23233732). Up-regulated upon hypertonic conditions (PubMed:23233732). Up-regulated in the dopamine D1 and D2 receptor-containing neurons of nucleus accumbens shell after spinal nerve ligation (PubMed:29993042).|||Monomer or homodimer; in equilibrium. Is tethered on endothelial cells by glycosaminoglycan (GAG) side chains of proteoglycans. Interacts with TNFAIP6 (via Link domain).|||N-Glycosylated.|||Processing at the N-terminus can regulate receptor and target cell selectivity (By similarity). Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant (By similarity).|||Secreted|||The polymorphisms in strain SJL/J may be associated with severity of clinical symptoms of experimental allergic encephalomyelitis, an animal model of multiple sclerosis, and susceptibility to the monophasic remitting/nonrelapsing form of the disease. http://togogenome.org/gene/10090:Mylpf ^@ http://purl.uniprot.org/uniprot/P97457 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subunit ^@ Deficient mice completely lack skeletal muscle and die immediately after birth because of respiratory failure.|||Myosin is a hexamer of 2 heavy chains and 4 light chains.|||Myosin regulatory subunit that plays an essential role to maintain muscle integrity during early development (PubMed:17356007). Plays a role in regulation of muscle contraction (By similarity).|||This chain binds calcium. http://togogenome.org/gene/10090:Plch1 ^@ http://purl.uniprot.org/uniprot/Q4KWH5 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain and to a lower extent in lung. In brain, it is found in cerebrum, cerebellum and spinal cord.|||Membrane|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes. http://togogenome.org/gene/10090:Net1 ^@ http://purl.uniprot.org/uniprot/Q9Z206 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase. May be involved in activation of the SAPK/JNK pathway. Stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.|||Can be converted to an oncogenic protein by N-terminal deletion that leads to nuclear export and cytoplasmic localization. Transformation seems to require the activity of multiple signaling pathways. The physiological conditions for cytoplasmic relocalization are not known yet.|||Cytoplasm|||Interacts with RHOA in its GTP- and GDP-bound states, and with CDC42 in its GTP-bound state. Interacts with the PDZ 1 domain of BAIAP1.|||Nucleus|||The PH domain is sufficient for the nuclear export of the oncogenic N-terminal truncated form. The relocalization is not affected by the Leu-492 mutation. http://togogenome.org/gene/10090:Gng11 ^@ http://purl.uniprot.org/uniprot/P61953 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma. Interacts with beta-1 and beta-3, but not with beta-2 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity). http://togogenome.org/gene/10090:Or1l4 ^@ http://purl.uniprot.org/uniprot/Q8VFT2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pdc ^@ http://purl.uniprot.org/uniprot/Q9QW08 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosducin family.|||Inhibits the transcriptional activation activity of the cone-rod homeobox CRX (By similarity). May participate in the regulation of visual phototransduction or in the integration of photoreceptor metabolism.|||Interacts with CRX (By similarity). Forms a complex with the beta and gamma subunits of the GTP-binding protein, transducin.|||Light-induced changes in cyclic nucleotide levels modulate the phosphorylation of this protein by cAMP kinase.|||Nucleus|||Photoreceptor inner segment|||cytosol|||photoreceptor outer segment http://togogenome.org/gene/10090:Nf2 ^@ http://purl.uniprot.org/uniprot/P46662|||http://purl.uniprot.org/uniprot/Q3TIW4|||http://purl.uniprot.org/uniprot/Q9D3K3 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cell projection|||Interacts with NHERF1, HGS and AGAP2. Interacts with SGSM3. Interacts (via FERM domain) with MPP1 (By similarity). Interacts with LAYN (PubMed:15913605). Interacts with WWC1. Interacts with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. The unphosphorylated form interacts (via FERM domain) with VPRBP/DCAF1. Interacts (via FERM domain) with NOP53; the interaction is direct (By similarity). Interacts with SCHIP1; the interaction is direct (By similarity).|||Membrane|||Mice are born with abnormally small lenses with serious structural defects. Failure of lens vesicle separation and the resulting changes in cell organization causes lenses to herniate, leading to expulsion of lens fiber cells through a perforation in the cornea. Developing lenses show loss of cell apical-basal polarity, failure of the lens vesicle to separate from the surface ectoderm, failure to properly exit the cell cycle during fiber cell differentiation and incomplete terminal differentiation of fiber cells.|||Nucleus|||Phosphorylation of Ser-518 inhibits nuclear localization by disrupting the intramolecular association of the FERM domain with the C-terminal tail. The dephosphorylation of Ser-518 favors the interaction with NOP53.|||Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex (By similarity). Plays a role in lens development and is required for complete fiber cell terminal differentiation, maintenance of cell polarity and separation of the lens vesicle from the corneal epithelium.|||Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-protein ligase complex for ubiquitination and subsequent proteasome-dependent degradation.|||cytoskeleton http://togogenome.org/gene/10090:Sox21 ^@ http://purl.uniprot.org/uniprot/Q811W0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Expression of ameloblastin AMBN is significantly reduced in the tooth germ of postnatal day 1 (P1) molars, but ASCL5/AmeloD expression is not altered.|||Highly expressed in both pre-secretory and secretory differentiated ameloblasts in molars at postnatal day 1 (P1).|||May play a role as an activator of transcription of OPRM1 (PubMed:12446692). Overexpression of SOX21 can up-regulate the OPRM1 distal promoter activity in mor-expressing neuronal cells (PubMed:12446692). May play a role in ameloblast differentiation (PubMed:34812512).|||Nucleus http://togogenome.org/gene/10090:Ddx24 ^@ http://purl.uniprot.org/uniprot/F8WJA0|||http://purl.uniprot.org/uniprot/Q9ESV0 ^@ Domain|||Function|||Similarity ^@ ATP-dependent RNA helicase.|||Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX24/MAK5 subfamily.|||RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis. http://togogenome.org/gene/10090:Stk39 ^@ http://purl.uniprot.org/uniprot/A2AQL0|||http://purl.uniprot.org/uniprot/Q9Z1W9 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated following phosphorylation at Thr-243 by WNK kinases (WNK1, WNK2, WNK3 or WNK4).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16382158, PubMed:17488636, PubMed:19633012, PubMed:21486947). Specifically recognizes and binds proteins with a RFXV motif (PubMed:14563843). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:14563843, PubMed:16382158, PubMed:17488636, PubMed:19633012, PubMed:21486947). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (By similarity). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (By similarity). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:17488636, PubMed:19633012, PubMed:21486947). Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities (PubMed:21317537, PubMed:23542070). Phosphorylates RELT (PubMed:16530727).|||Expressed in the kidney, including in epithelial cells of the thick ascending limb of Henle's loop and in the distal convoluted tubule (at protein level).|||Nucleus|||PAPA box (proline-alanine repeats) may target the kinase to a specific subcellular location by facilitating interaction with intracellular proteins such as actin or actin-like proteins.|||Phosphorylation at Thr-243 by WNK kinases (WNK1, WNK2, WNK3 or WNK4) is required for activation (PubMed:16382158, PubMed:21486947). Autophosphorylation at Thr-243 positively regulates its activity (PubMed:16530727). Phosphorylated at Ser-321 by PRKCQ (PubMed:21733846).|||The phosphorylated form forms a complex with WNK2 (PubMed:21733846). Interacts with RELT (PubMed:16530727). Interacts with SORL1 (via cytosolic C-terminus) (By similarity). http://togogenome.org/gene/10090:Rdh12 ^@ http://purl.uniprot.org/uniprot/Q8BYK4 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Deficient mice are fertile and developed normally. Deficient mice exhibit normal retinal function at 6 weeks, but they show increased susceptibility to retinal cell apoptosis of both cone and rod photoreceptors induced by high intensity illumination (PubMed:17032653). All- trans-retinol production in inner and outer segments of the photoreceptor is not affected in deficient mice (PubMed:22621924).|||Expressed in the inner segments of the photoreceptor in retina.|||Retinoids dehydrogenase/reductase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinal. Shows very weak activity toward 13-cis-retinol. Also exhibits activity, albeit with lower affinity than for retinaldehydes, towards lipid peroxidation products (C9 aldehydes) such as 4-hydroxynonenal and trans-2-nonenal (By similarity). Plays an important function in photoreceptor cells to detoxify 4-hydroxynonenal and potentially other toxic aldehyde products resulting from lipid peroxidation (PubMed:19686838, PubMed:22621924, PubMed:17032653). Has no dehydrogenase activity towards steroids (By similarity).|||Shows clear specificity for the pro-S hydrogen on C4 of NADPH and the pro-R hydrogen on C15 of retinols. http://togogenome.org/gene/10090:Teddm2 ^@ http://purl.uniprot.org/uniprot/Q208S0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Membrane http://togogenome.org/gene/10090:Dlgap4 ^@ http://purl.uniprot.org/uniprot/B1AZP2|||http://purl.uniprot.org/uniprot/B7ZNS2|||http://purl.uniprot.org/uniprot/E9PUF2|||http://purl.uniprot.org/uniprot/Q3UCF7 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SAPAP family.|||Interacts with DLG1 and DLG4/PSD-95.|||Intron retention.|||May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/SAP90 at the plasma membrane (By similarity).|||Membrane http://togogenome.org/gene/10090:Cabyr ^@ http://purl.uniprot.org/uniprot/Q9D424 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in spermatozoa.|||Interacts with FSCB.|||May function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction. May bind calcium in vitro (By similarity).|||Phosphorylated on tyrosine residues during in vitro capacitation. Dephosphorylation affects its ability to bind calcium (By similarity).|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Pstk ^@ http://purl.uniprot.org/uniprot/Q8BP74 ^@ Function|||Similarity ^@ Belongs to the L-seryl-tRNA(Sec) kinase family.|||Specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis. No activity with other tRNAs has been detected. http://togogenome.org/gene/10090:Utp11 ^@ http://purl.uniprot.org/uniprot/Q9CZJ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UTP11 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA.|||nucleolus http://togogenome.org/gene/10090:Ly6i ^@ http://purl.uniprot.org/uniprot/Q9WU67 ^@ Polymorphism|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in hematopoietic tissue (spleen, thymus, bone marrow). Also found in peritoneal macrophages, peripheral blood leukocytes, liver, heart, brain, kidney and lung.|||Ly-6I.2 and Ly-6I.1 are expressed in bone marrow of strain C57BL/6 and strain NOD, respectively. http://togogenome.org/gene/10090:Ifna13 ^@ http://purl.uniprot.org/uniprot/A0A7R8C3J8|||http://purl.uniprot.org/uniprot/Q80SU4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Exhibits antiviral activity against Theiler's virus, Mengo virus and vesicular stomatitis virus. Interferons alpha stimulate the production of two enzymes: a protein kinase and an oligoadenylate synthetase.|||Secreted|||Transcribed constitutively. Not induces by viral infection. http://togogenome.org/gene/10090:Sfrp4 ^@ http://purl.uniprot.org/uniprot/Q9Z1N6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the secreted frizzled-related protein (sFRP) family.|||Expressed in the ovary. Localized to granulosa cells of periovulatory follicles and corpora lutea. Weakly expressed in adult tissues including kidney, brain and lung.|||Induced in ovaries by chorionic gonadotropin (CG).|||Mice laking Sfrp4 have increased trabecular bone, reduced cortical-bone thickness, and failure of bone modeling during growth, resulting in wider bones with thinner and mechanically inadequate cortexes.|||Only weakly expressed in developing embryo except for developing teeth, eye and salivary gland. In the developing eye, from 12.5 dpc, expressed in the future neural retina, in both the inner and outer cell layers. In the developing teeth, strong expression detected in the developing incisor teeth at 14.5 dpc. Expression localized to the mesenchyme of the dental follicle surrounding the enamel organ only at the early cap stage. Highly expressed in the branching epithelium of the salivary gland.|||Secreted|||Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (PubMed:27355534). SFRP4 plays a role in bone morphogenesis (PubMed:27355534). May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (By similarity).|||The FZ domain is involved in binding with Wnt ligands. http://togogenome.org/gene/10090:Rmi2 ^@ http://purl.uniprot.org/uniprot/Q3UPE3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RMI2 family.|||Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM (By similarity).|||Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates. It is required to regulate sister chromatid segregation and to limit DNA crossover. Essential for the stability, localization, and function of BLM, TOP3A, and complexes containing BLM. In the RMI complex, it is required to target BLM to chromatin and stress-induced nuclear foci and mitotic phosphorylation of BLM.|||Nucleus|||Phosphorylated during mitosis. http://togogenome.org/gene/10090:Dolpp1 ^@ http://purl.uniprot.org/uniprot/A2AWJ3|||http://purl.uniprot.org/uniprot/Q9JMF7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the dolichyldiphosphatase family.|||Endoplasmic reticulum membrane|||Membrane|||Required for efficient N-glycosylation. Necessary for maintaining optimal levels of dolichol-linked oligosaccharides. Hydrolyzes dolichyl pyrophosphate at a very high rate and dolichyl monophosphate at a much lower rate. Does not act on phosphatidate.|||Widely expressed with highest levels in brain, kidney, lung and intestine. http://togogenome.org/gene/10090:Ckap2 ^@ http://purl.uniprot.org/uniprot/Q3V1H1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with alpha- and beta-tubulins.|||Belongs to the CKAP2 family.|||By constitutively activated RET proteins. By p53/TP53.|||Possesses microtubule stabilizing properties. Involved in regulating aneuploidy, cell cycling, and cell death in a p53-dependent manner.|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Arhgef15 ^@ http://purl.uniprot.org/uniprot/Q5FWH6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At P12, expressed is detected in the CA1 region and the dentate gyrus of the hippocampus.|||Highest levels in hippocampus are found at postnatal day 3 prior to maximal synapse formation and decrease as synapse formation peaks in the postnatal period (at protein level).|||In a mouse model of Angelman syndrome where Ube3a levels are reduced, levels of Arhgef15 are significantly increased and ubiquitination is reduced compared to wild-type litter mates.|||Interacts with EPHA4 (By similarity). Interacts with EPHB2.|||Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-dependent phosphorylation at Tyr-361 triggers UBE3A-mediated ubiquitination.|||Significant decrease in RHOA activation in brain extracts.|||Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2.|||Ubiquitinated; UBE3A-mediated ubiquitination and degradation by the proteasome promotes EFNB1-dependent synapse formation.|||dendrite http://togogenome.org/gene/10090:P2ry10b ^@ http://purl.uniprot.org/uniprot/Q8BY68 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cdkl1 ^@ http://purl.uniprot.org/uniprot/Q14BG3|||http://purl.uniprot.org/uniprot/Q8CEQ0 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Nucleus|||The [NKR]KIAxRE motif seems to be a cyclin-binding region. http://togogenome.org/gene/10090:Sart1 ^@ http://purl.uniprot.org/uniprot/Q9Z315 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNU66/SART1 family.|||Expressed at maximal level at 12 dpc. Declines progressively until birth.|||Identified in the spliceosome C complex. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Interacts with UBL5.|||Nucleus|||Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA.|||Sumoylated with SUMO2.|||Ubiquitously expressed. Shows a high expression in fetal liver and a low expression in adult liver. http://togogenome.org/gene/10090:Frat2 ^@ http://purl.uniprot.org/uniprot/Q8K025 ^@ Function|||Similarity|||Subunit ^@ Belongs to the GSK-3-binding protein family.|||Binds GSK-3 and prevents GSK-3-dependent phosphorylation.|||Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. http://togogenome.org/gene/10090:Pou2af2 ^@ http://purl.uniprot.org/uniprot/Q9D8Q6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU2AF family.|||Expressed in tuft cells of the small intestine, trachea, thymus, and colon.|||In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif (5'-ATGAAAT-3').|||Interacts with POU2F3 (via the POU domain) in a DNA-dependent manner; this interaction recruits POU2AF2 to chromatin and increases POU2F3 transactivation activity.|||Mutant mice generated by CRISPR-Cas9-mediated gene editing are born at normal Mendelian ratios, and have indistinguishable weight, morphology, fertility, and organ histology from normal mice. However, tuft cells in the trachea, small intestine, urethra, gall bladder, tongue, and nasal epithelium are indetectable in Pou2af2-/- mice, whereas a partial loss of tuft cells is observed in the colon.|||Nucleus|||Transcriptional coactivator of POU2F3 (By similarity). This complex drives the development of tuft cells, a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues (PubMed:35576971).|||cytosol http://togogenome.org/gene/10090:Ripk1 ^@ http://purl.uniprot.org/uniprot/Q60855 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with Murid herpesvirus 1 protein RIR1.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cell membrane|||Cytoplasm|||Deubiquitinated by USP7; this modification is required for TNF-alpha-induced apoptosis.|||Found at low levels in all tissues.|||Homodimer (PubMed:29440439). Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necroptosis-inducing complex (PubMed:31519887, PubMed:28842570). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity (By similarity). Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain) (By similarity). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process (By similarity). Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3 (By similarity). Interacts with BNLF1 (By similarity). Interacts with SQSTM1 upon TNF-alpha stimulation (By similarity). May interact with MAVS/IPS1 (By similarity). Interacts with ZFAND5 (By similarity). Interacts with RBCK1 (By similarity). Interacts with ZBP1 (PubMed:19590578, PubMed:23283962, PubMed:33397971). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner (By similarity). Interacts with ARHGEF2 (By similarity). Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination (By similarity). Interacts with RNF34; involved in RIPK1 ubiquitination (By similarity). Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (By similarity). Interacts with PELI1 (PubMed:29883609). Interacts (via death domain) with CRADD (via death domain); the interaction is direct (By similarity). Component of complex IIa composed of at least RIPK1, FADD and CASP8 (PubMed:29440439). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287). Interacts with MAP3K7, CFLAR and CASP8 (PubMed:31519887). Interacts with FADD (PubMed:29440439, PubMed:31519887, PubMed:28842570). Interacts with NEMO (PubMed:31519886). Interacts with TAX1BP1; this interaction negatively regulates RIPK1 ubiquitination (PubMed:18239685).|||In concanavalin A-treated splenocytes.|||Mice exhibit severe multi-organ inflammation and systemic cell death, which causes lethality of animals late in gestation or shortly after birth (PubMed:24813849, PubMed:30185824). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Ripk3; mice however die the first days of postnatal life (PubMed:24813849, PubMed:24813850, PubMed:27819681, PubMed:27819682). Perinatal lethality observed in Ripk1 knockout mice is rescued in knockout mice lacking both Ripk1 and Casp8; mice however die the first days of postnatal life (PubMed:24813849). Only mice lacking Ripk1, Ripk3 and Casp8 survive past weaning and rescue lethality caused by the absence of Ripk1 (PubMed:24813849, PubMed:24813850).|||Proteolytically cleaved by CASP8 at Asp-325 (PubMed:30867408, PubMed:31511692, PubMed:31827280). Cleavage is crucial for limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:30867408, PubMed:31511692, PubMed:31827281, PubMed:31827280). Cleavage abolishes NF-kappa-B activation and enhances the interaction of TRADD with FADD (By similarity). Proteolytically cleaved by CASP6 during intrinsic apoptosis (By similarity).|||RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex (By similarity). Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (PubMed:30988283). Phosphorylated at Ser-321 by MAP3K7 which requires prior ubiquitination with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 (PubMed:28842570). This phosphorylation positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (PubMed:28842570).|||Serine-threonine kinase activity is inhibited by linear polyubiquitination ('Met-1'-linked) by the LUBAC complex.|||Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:27819681, PubMed:28842570, PubMed:31511692, PubMed:31827280, PubMed:31827281, PubMed:33397971). Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:24813849, PubMed:24813850, PubMed:24557836, PubMed:28842570, PubMed:31519886, PubMed:31519887). Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (PubMed:31519886, PubMed:31519887). Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (PubMed:28842570, PubMed:27819681, PubMed:27819682, PubMed:29440439, PubMed:30988283, PubMed:31519886, PubMed:31519887). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (PubMed:24813849, PubMed:24813850, PubMed:24557836). In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:24557836, PubMed:27819681, PubMed:27819682, PubMed:31358656). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:31358656). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (PubMed:30867408, PubMed:30185824). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (By similarity). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (By similarity). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (PubMed:12654725, PubMed:19590578).|||The RIP homotypic interaction motif (RHIM) mediates interaction with the RHIM motif of RIPK1. Both motifs form a hetero-amyloid serpentine fold, stabilized by hydrophobic packing and featuring an unusual Cys-Ser ladder of alternating Ser (from RIPK1) and Cys (from RIPK3).|||The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (By similarity).|||Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin (By similarity). Polyubiquitination with 'Lys-63'-linked chains by TRAF2 induces association with the IKK complex (By similarity). Deubiquitination of 'Lys-63'-linked chains and polyubiquitination with 'Lys-48'-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-alpha-induced NF-kappa-B signaling (By similarity). 'Lys-48'-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NF-kappa-B signaling (By similarity). Linear polyubiquitinated; the head-to-tail linear polyubiquitination ('Met-1'-linked) is mediated by the LUBAC complex and decreases protein kinase activity (PubMed:28701375). Deubiquitination of linear polyubiquitin by CYLD promotes the kinase activity (PubMed:28701375). Polyubiquitinated with 'Lys-48' by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B (By similarity). Ubiquitinated with 'Lys-63'-linked chains by PELI1 (By similarity). Ubiquitination at Lys-376 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-321 mediated by MAP3K7 (PubMed:28842570, PubMed:31519887, PubMed:31519886). This ubiquitination is required for NF-kB activation, suppresses RIPK1 kinase activity and plays a critical role in preventing cell death during embryonic development (PubMed:31519887, PubMed:31519886). http://togogenome.org/gene/10090:Emp1 ^@ http://purl.uniprot.org/uniprot/P47801|||http://purl.uniprot.org/uniprot/Q05BR0|||http://purl.uniprot.org/uniprot/Q4FK43 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Mesd ^@ http://purl.uniprot.org/uniprot/Q9ERE7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MESD family.|||Chaperone specifically assisting the folding of beta-propeller/EGF modules within the family of low-density lipoprotein receptors (LDLRs) (PubMed:31564437). Acts as a modulator of the Wnt pathway through chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and LRP6, to the plasma membrane. Essential for specification of embryonic polarity and mesoderm induction (PubMed:12581525, PubMed:21397183). Plays an essential role in neuromuscular junction (NMJ) formation by promoting cell-surface expression of LRP4 (PubMed:24140340). May regulate phagocytosis of apoptotic retinal pigment epithelium (RPE) cells.|||Disruption of embryonic polarity and mesoderm differentiation, likely resulting from a primary defect in Wnt signaling.|||Endoplasmic reticulum|||Expressed in many tissues, but not in skeletal muscles (PubMed:11247670). In the retina expressed in retinal ganglion cells, inner and outer plexiform layers, photoreceptor inner and outer segments and retinal pigment epithelium (at protein level) (PubMed:27184668).|||Monomer. Interacts with LRP5; the interaction prevents LRP5 from forming aggregates and chaperones LRP6 to the plasma membrane. Interacts with LRP6; the interaction prevents LRP6 from forming aggregates and chaperones LRP6 to the plasma membrane. Interacts with LRP4; the interaction promotes glycosylation of LRP4 and its cell-surface expression (PubMed:24140340).|||The chaperone domain provides a folding template for proper folding of the beta-propeller (BP) domains of LRP5/6.|||The escort domain ensures LRP5/6 safe-trafficking from the ER to the Golgi by preventing premature ligand-binding. http://togogenome.org/gene/10090:Phf11d ^@ http://purl.uniprot.org/uniprot/A6H5X4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with BRCA1 and RELA.|||Nucleus|||Positive regulator of Th1-type cytokine gene expression. http://togogenome.org/gene/10090:Cbarp ^@ http://purl.uniprot.org/uniprot/Q66L44 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in brain from 14 dpc until adulthood with higher expression between 18 dpc and P7 (at protein level).|||Expressed by neurons in the cortex, cerebellum and hippocampus and by pancreatic beta cells (at protein level).|||Interacts with voltage-dependent calcium channels CACNB1, CACNB2, CACNB3 and CACNB4 beta subunits; prevents their interaction with the CACNA1C alpha subunit thereby negatively regulating the activity of the corresponding calcium channels.|||Negatively regulates voltage-gated calcium channels by preventing the interaction between their alpha and beta subunits. Thereby, negatively regulates calcium channels activity at the plasma membrane and indirectly inhibits calcium-regulated exocytosis.|||Probable cloning artifact.|||growth cone|||synaptic vesicle membrane http://togogenome.org/gene/10090:Dnah7c ^@ http://purl.uniprot.org/uniprot/A0A087WR13 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:H3c14 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Etf1 ^@ http://purl.uniprot.org/uniprot/Q3TF02|||http://purl.uniprot.org/uniprot/Q8BWY3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with Moloney murine leukemia virus (MoLV) reverse transcriptase/Ribonuclease H p80 (via RT and RNase domains); this interaction is essential for translational readthrough of amber codon between viral gag and pol genes. Interacts with MoLV Gag-Pol precursor.|||Belongs to the eukaryotic release factor 1 family.|||Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons. The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site. ETF1/ERF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA. Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site, followed by hydrolysis of peptidyl-tRNA. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes.|||Component of the eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Interacts with JMJD4. The ETF1-GSPT1 complex interacts with JMJD4.|||Cytoplasm|||Hydroxylation at Lys-63 by JMJD4 promotes its translational termination efficiency.|||Methylated at Gln-185 by N6AMT1.|||Ubiquitinated via 'Lys-6'-linked polyubiquitin chains by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling), leading to its degradation by the proteasome and rescue of stalled ribosomes. http://togogenome.org/gene/10090:Sit1 ^@ http://purl.uniprot.org/uniprot/Q8C503 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in thymus and spleen, with highest levels in immature thymocytes (at protein level).|||Homodimer; disulfide-linked. When phosphorylated, interacts with PTPN11/SHP2, GRB2 and CSK (By similarity).|||Mice are viable and fertile, with normal growth and no obvious abnormalities. They show normal B-cell development and peripheral B-cell functions, but have mildly altered thymic development probably due to enhanced TCR signaling. This results in a greater susceptibility to autoimmune diseases.|||Negatively regulates T-cell antigen receptor (TCR)-mediated signaling. Involved in positive selection of T-cells.|||Phosphorylated on tyrosines upon TCR activation; which leads to the recruitment of PTPN11, GRB2 and CSK. http://togogenome.org/gene/10090:Fyn ^@ http://purl.uniprot.org/uniprot/P39688 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated at Tyr-420 (PubMed:8441403). Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state (PubMed:8441403). PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-15 and kinase activity, and promotes translocation from the cytoplasm to the nucleus. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling (By similarity). Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (PubMed:22685302).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Cytoplasm|||Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site.|||Interacts (via its SH3 domain) with PIK3R1 and PRMT8 (By similarity). Interacts with FYB1, PAG1, and SH2D1A (By similarity). Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity (PubMed:8168489). Interacts with TOM1L1 (phosphorylated form) (PubMed:11711534). Interacts with SH2D1A and SLAMF1 (By similarity). Interacts with and phosphorylates ITCH, down-regulating its activity (By similarity). Interacts with FASLG (By similarity). Interacts with RUNX3 (By similarity). Interacts with KIT (By similarity). Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion (By similarity). Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation (By similarity). Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway (By similarity). Interacts (via SH3 domain) with KLHL2 (via N-terminus) (By similarity). Interacts with KDR (tyrosine phosphorylated) (PubMed:16966330). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:7681396, PubMed:9312046). Interacts with UNC119 (By similarity). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064). Interacts with PTPRO (phosphorylated form) (PubMed:20398064). Interacts with PTPRB (phosphorylated form) (PubMed:20398064). Interacts with FYB2 (By similarity). Interacts with DSCAM (PubMed:22685302). Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK (PubMed:12681493). Interacts with NEDD9; in the presence of PTK2 (By similarity).|||Isoform 1 is highly expressed in the brain, isoform 2 is expressed in cells of hemopoietic lineages, especially T-lymphocytes.|||Mice have various neural defects, including defective long term potentiation, impaired spatial memory, hypomyelination, abnormal dendrite orientation and uncoordinated hippocampal structure.|||Myristoylation is required prior to palmitoylation.|||Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (PubMed:12681493).|||Nucleus|||Palmitoylated (PubMed:19956733, PubMed:7980442, PubMed:8413237, PubMed:9201723). Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location (PubMed:7980442, PubMed:8413237, PubMed:9201723, PubMed:19956733).|||Perikaryon http://togogenome.org/gene/10090:Tceanc2 ^@ http://purl.uniprot.org/uniprot/Q8R2M0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TCEANC2 family.|||Nucleus http://togogenome.org/gene/10090:Mmp16 ^@ http://purl.uniprot.org/uniprot/Q9WTR0 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M10A family.|||Binds 2 zinc ions per subunit.|||Cell membrane|||Endopeptidase that degrades various components of the extracellular matrix, such as collagen type III and fibronectin. Activates progelatinase A. Involved in the matrix remodeling of blood vessels. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells (By similarity).|||Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase. http://togogenome.org/gene/10090:Or8a1b ^@ http://purl.uniprot.org/uniprot/Q8VGE3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Spock2 ^@ http://purl.uniprot.org/uniprot/Q9ER58 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Brain specific.|||May participate in diverse steps of neurogenesis. Binds calcium (By similarity).|||O-glycosylated; contains chondroitin sulfate and heparan sulfate.|||extracellular matrix http://togogenome.org/gene/10090:Abca5 ^@ http://purl.uniprot.org/uniprot/Q8K448 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCA family.|||Cell membrane|||Cholesterol efflux transporter in macrophages that is responsible for APOAI/high-density lipoproteins (HDL) formation at the plasma membrane under high cholesterol levels and participates in reverse cholesterol transport (PubMed:25125465, PubMed:32687853, PubMed:20382126). May play a role in the processing of autolysosomes (PubMed:15870284).|||Down-regulated by digoxin (PubMed:16445568). Up-regulated by an excess cellular cholesterol level (PubMed:32687853). Up-regulated when ABCA1 is down-regulated (PubMed:32687853).|||Expressed during embryogenesis.|||Expressed in cardiomyocytes, oligodendrocytes and astrocytes in brain, alveolar type 2 cells in lung and follicular cells in the thyroid gland (at protein level). Detected in brain, testis, lung, heart, liver, kidney, skeletal muscle and placenta. Strongly expressed in the basal cells of the seminiferous tubules, interstitial cells consisting of Leydig cells, as well as the tunica albuginea (PubMed:24831815). In the epididymis, specificly and very strongly expressed in the connective tissue outlining the cylindrical epithelium in the corpus and cauda regions, including fibrocytes and smooth muscle cells, as well as within the basal and tall columnar cells of the corpus cylindrical epithelium (PubMed:24831815). Highly expressed in the brain with high expression in cortical and hippocampal neurons and moderately in the lung (PubMed:25125465).|||Golgi apparatus membrane|||Late endosome membrane|||Lysosome membrane|||Mice display hypothyroidism and lethal heart abnormalities that may be due to altered autolysosomes processing.|||N-glycosylated. http://togogenome.org/gene/10090:Or6c211 ^@ http://purl.uniprot.org/uniprot/Q8VEU1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hoxc11 ^@ http://purl.uniprot.org/uniprot/P31313 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Capn11 ^@ http://purl.uniprot.org/uniprot/Q6J756 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C2 family.|||Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.|||Expressed exclusively in testis, where it is restricted to spermatocytes and during the later stages of meiosis (at protein level).|||Heterodimer of a large (catalytic) and a small (regulatory) subunit.|||acrosome http://togogenome.org/gene/10090:Tpx2 ^@ http://purl.uniprot.org/uniprot/A2APB8|||http://purl.uniprot.org/uniprot/Q8BTJ3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TPX2 family.|||Expressed during all phases of oocyte maturation; localized at the meiotic spindle and microtubule organizing center during meiosis.|||Interacts with AURKA (PubMed:18663142). Interacts with importin-alpha; leading to inactivate TPX2 (By similarity). Interacts with HNRNPU; this interaction recruits HNRNPU to spindle microtubules (MTs) (By similarity). Interacts with BCL2L10 (PubMed:27753540).|||Nucleus|||Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules. Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation. TPX2 is inactivated upon binding to importin-alpha. At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activates AURKA kinase and stimulates local microtubule nucleation.|||spindle|||spindle pole http://togogenome.org/gene/10090:Bnip3 ^@ http://purl.uniprot.org/uniprot/O55003 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2 (By similarity). Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane may play a critical role in the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix (By similarity). The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix (By similarity). Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway (By similarity).|||Belongs to the NIP3 family.|||Homodimer. Binds to BCL2. Interacts with BNIP3L and ACAA2. Interacts (via BH3 domain) with SPATA18 (via coiled-coil domains). Interacts with BOK; promotes BOK oligomerization.|||Mitochondrion|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Slc52a2 ^@ http://purl.uniprot.org/uniprot/Q9D8F3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the riboflavin transporter family.|||Cell membrane|||Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism. May also act as a receptor for 4-hydroxybutyrate.|||Riboflavin transport is Na(+)-independent but moderately pH-sensitive (By similarity). Activity is strongly inhibited by riboflavin analogs, such as lumiflavin (By similarity). Weakly inhibited by flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) (By similarity). http://togogenome.org/gene/10090:Timm9 ^@ http://purl.uniprot.org/uniprot/Q9WV98 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small Tim family.|||Heterohexamer; composed of 3 copies of TIMM9 and 3 copies of TIMM10/TIM10A, named soluble 70 kDa complex. The complex forms a 6-bladed alpha-propeller structure and associates with the TIMM22 component of the TIM22 complex. Interacts with multi-pass transmembrane proteins in transit. Also forms a complex composed of TIMM9, TIMM10/TIM10A and FXC1/TIM10B (By similarity).|||Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity).|||Mitochondrion inner membrane|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). http://togogenome.org/gene/10090:Or2a56 ^@ http://purl.uniprot.org/uniprot/Q8VFS6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krt27 ^@ http://purl.uniprot.org/uniprot/Q9Z320 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Essential for the proper assembly of type I and type II keratin protein complexes and formation of keratin intermediate filaments in the inner root sheath (irs).|||Expressed in skin. Expressed in the Henle layer and cuticle of the irs in hair follicle bulb. In the hair follicle, expression was observed in all layers of the irs but was stronger in the Henle layer and cuticle than the Huxley layer until the Henle layer differentiated (at protein level).|||Heterotetramer of two type I and two type II keratins. Interacts with KRT6A to form filaments.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Gpr34 ^@ http://purl.uniprot.org/uniprot/Q3YL73|||http://purl.uniprot.org/uniprot/Q9R1K6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Broadly expressed.|||Cell membrane|||Membrane|||Orphan receptor. http://togogenome.org/gene/10090:Or10ag56 ^@ http://purl.uniprot.org/uniprot/A0A0J9YUE7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccz1 ^@ http://purl.uniprot.org/uniprot/Q8C1Y8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts in concert with MON1A, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form.|||Belongs to the CCZ1 family.|||Interacts with MON1A. Found in a complex with RMC1, CCZ1 MON1A and MON1B.|||Lysosome membrane http://togogenome.org/gene/10090:Myh10 ^@ http://purl.uniprot.org/uniprot/Q3UH59|||http://purl.uniprot.org/uniprot/Q5SV64|||http://purl.uniprot.org/uniprot/Q61879 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||In newborn kidney, expressed in the mesenchyme and ureteric buds.|||Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2. During cell spreading, plays an important role in cytoskeleton reorganization, focal contacts formation (in the central part but not the margins of spreading cells), and lamellipodial extension; this function is mechanically antagonized by MYH9 (By similarity). Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.|||Myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2). Interacts with PLEKHG6 (By similarity). Interacts with ECPAS (By similarity). Interacts with LARP6 (By similarity). Interacts with MCC (By similarity). Interacts with KIF26B (PubMed:20439720). Interacts with CFAP95 (By similarity).|||Phosphorylated by ABL2.|||Represents a conventional non-muscle myosin. This protein should not be confused with the unconventional myosin-10 (MYO10).|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||lamellipodium http://togogenome.org/gene/10090:Rnf122 ^@ http://purl.uniprot.org/uniprot/Q8BP31 ^@ Function|||Subcellular Location Annotation ^@ Endoplasmic reticulum|||Golgi apparatus|||May induce necrosis and apoptosis. May play a role in cell viability (By similarity).|||Membrane http://togogenome.org/gene/10090:Padi1 ^@ http://purl.uniprot.org/uniprot/Q544I4|||http://purl.uniprot.org/uniprot/Q9Z185 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein arginine deiminase family.|||By estrogen.|||Catalyzes the deimination of arginine residues of proteins.|||Cytoplasm|||Expressed during the estrus cycle. Expression is maximum at proestrus and moderate at estrus. Not expressed in diestrus and metaestrus phases.|||Expressed only in the epidermis and uterus.|||Monomer. http://togogenome.org/gene/10090:Lmtk2 ^@ http://purl.uniprot.org/uniprot/Q3TYD6 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Expression observed during all tested stages from 18 dpc to postnatal week 6, but it was especially high during the early postnatal stage (postnatal weeks 0-2).|||Interacts with PPP1C and inhibitor-2.|||Mainly expressed in brain, especially in the olfactory bulb, olfactory tubercle, hippocampus, striatum, cerebellum and cerebral cortex. Weakly expressed in skeletal muscle and not expressed in liver.|||Membrane|||Phosphorylates PPP1C, phosphorylase b and CFTR. http://togogenome.org/gene/10090:Spin2f ^@ http://purl.uniprot.org/uniprot/A0A571BGB0 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Neto2 ^@ http://purl.uniprot.org/uniprot/Q8BNJ6 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory subunit of neuronal kainate-sensitive glutamate receptors, GRIK2 and GRIK3. Increases kainate-receptor channel activity, slowing the decay kinetics of the receptors, without affecting their expression at the cell surface, and increasing the open probability of the receptor channels. Modulates the agonist sensitivity of kainate receptors. Slows the decay of kainate receptor-mediated excitatory postsynaptic currents (EPSCs), thus directly influencing synaptic transmission (By similarity).|||Cell membrane|||Expressed in brain tissues, including cerebellar granule cells (at protein level).|||Interacts with GRIK2 and GRIK3, but neither with AMPA-nor with NMDA-sensitive glutamate receptors.|||N-glycosylated.|||Observed restrictively in brain throughout embryonic (E) and postnatal stages (P). Expression pattern in brain slightly changes from 13 dpc to P21. http://togogenome.org/gene/10090:Vsx1 ^@ http://purl.uniprot.org/uniprot/A2AQX5|||http://purl.uniprot.org/uniprot/Q91V10 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At embryonic day 14.5 ocular morphology is normal as is expression and localization of retinal transcription and cell cycle regulatory proteins.|||Belongs to the paired homeobox family.|||Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster (By similarity). May regulate the activity of the LCR and the cone opsin genes at earlier stages of development (By similarity). Dispensable in early retinal development (PubMed:17919464).|||Expressed at P5, solely within the inner nuclear layer (INL) of the central neuroretina. By days P6 and P7, expression expands peripherally during neurogenesis. By P12, expression is restricted to the outer margin of the INL and reaches the outer periphery of the neuroretina.|||Expressed in the postnatal retina (at protein level) (PubMed:17919464). In the adult, expressed exclusively in the cells of the neural retina with expression restricted to postnatal cone bipolar interneurons (PubMed:15838724).|||Nucleus http://togogenome.org/gene/10090:Cpa6 ^@ http://purl.uniprot.org/uniprot/Q5U901 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||In brain, highly expressed in the olfactory bulb with lower levels in other regions including cerebral cortex, hippocampus, hypothalamus, striatum and medulla. Within the olfactory bulb, highest levels occur in the mitral and granular layers with lower levels in the internal and external plexiform layers. Moderate levels are found in the epididymis with low levels in colon and spleen. Not detected in adrenal, liver, lung, ovary or testis. At embryonic day 14.5, enriched in eye, ear, osteoblasts, stomach, skin, dorsal root ganglia and throughout the CNS.|||May be involved in the proteolytic inactivation of enkephalins and neurotensin in some brain areas. May convert inactive angiotensin I into the biologically active angiotensin II. Releases a C-terminal amino acid, with preference for large hydrophobic C-terminal amino acids and shows only very weak activity toward small amino acids and histidine.|||extracellular matrix http://togogenome.org/gene/10090:Msh3 ^@ http://purl.uniprot.org/uniprot/A0A087WQ16|||http://purl.uniprot.org/uniprot/E9QPY6|||http://purl.uniprot.org/uniprot/P13705 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DNA mismatch repair MutS family.|||Belongs to the DNA mismatch repair MutS family. MSH3 subfamily.|||Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer consisting of MSH2-MSH3 (MutS beta). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Interacts with MCM9.|||Component of the post-replicative DNA mismatch repair system (MMR).|||Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis (By similarity). http://togogenome.org/gene/10090:Prickle2 ^@ http://purl.uniprot.org/uniprot/A7YQ68|||http://purl.uniprot.org/uniprot/Q80Y24 ^@ Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the prickle / espinas / testin family.|||Expressed in the hippocampus and cerebral cortex.|||Nucleus membrane|||Null mice are viable, but show an increased seizure rate compared to heterozygous mice, indicating a dosage effect. Heterozygous Prickle2 +/- mice have a decreased seizure threshold compared to wild-type. http://togogenome.org/gene/10090:Ccdc88c ^@ http://purl.uniprot.org/uniprot/Q6VGS5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC88 family.|||Cell junction|||Cytoplasm|||Homooligomer (PubMed:14750955). Interacts with DVL1 (via PDZ domain); dissociates following initiation of non-canonical Wnt signaling (PubMed:14750955). Interacts (via C-terminus) with ligand-activated Wnt receptor FZD7; competes with DVL1 for binding to FZD7 and displaces DVL1 from ligand-activated FZD7 (By similarity). Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunits GNAI1, GNAI2 and GNAI3 (inactive GDP-bound form); interacts with higher affinity with GNAI1 and GNAI3 than with GNAI2 and interaction leads to G(i) alpha subunit activation (By similarity). Does not interact with GNAO1 (By similarity).|||Required for activation of guanine nucleotide-binding proteins (G-proteins) during non-canonical Wnt signaling. Binds to ligand-activated Wnt receptor FZD7, displacing DVL1 from the FZD7 receptor and leading to inhibition of canonical Wnt signaling. Acts as a non-receptor guanine nucleotide exchange factor by also binding to guanine nucleotide-binding protein G(i) alpha (Gi-alpha) subunits, leading to their activation. Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex, triggering non-canonical Wnt responses such as activation of RAC1 and PI3K-AKT signaling. Promotes apical constriction of cells via ARHGEF18.|||The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).|||The PDZ domain is required for localization to apical junctions. http://togogenome.org/gene/10090:Ttc28 ^@ http://purl.uniprot.org/uniprot/Q80XJ3 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During mitosis, may be involved in the condensation of spindle midzone microtubules, leading to the formation of midbody.|||Essential for the formation and integrity of the midbody. Max play a critical role in the progress of mitosis and cytokinesis during cell cycle (By similarity).|||Expressed in embryos at all stages examined. In adult tissues, detected in heart and at low levels in kidney and testis.|||Interacts with AURKB.|||Midbody|||Several sequencing errors and erroneous CDS prediction.|||centrosome|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Nrbp1 ^@ http://purl.uniprot.org/uniprot/Q99J45 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Embryonic lethality by 7.5 dpc.|||Endomembrane system|||Expressed in Paneth, enteroendocrine and precursor goblet cell lineages in the intestine.|||Homodimer (PubMed:12176995). Binds to MLF1, recruiting a serine kinase which phosphorylates both itself and MLF1 (PubMed:12176995). Phosphorylated MLF1 binds to YWHAZ and is retained in the cytoplasm (PubMed:12176995). Interacts with ELOC/TCEB1, ELOB/TCEB2, TSC22D2 and TSC22D4 (By similarity). Interacts with the Elongin BC E3 ubiquitin ligase complex via its interaction with ELOB/TCEB2 and ELOC/TCEB1 (By similarity). Interacts with SALL4 (PubMed:22510880).|||May act as a tumor suppressor to decrease tumor incidence and improve survival.|||Required for embryonic development (PubMed:22510880). Plays a role in intestinal epithelial cell fate and proliferation, thereby involved in the architectural development of the intestine potentially via the regulation of Wnt-responsive genes (PubMed:22510880). May play a role in subcellular trafficking between the endoplasmic reticulum and Golgi apparatus through interactions with the Rho-type GTPases (By similarity).|||The protein kinase domain is predicted to be catalytically inactive.|||cell cortex|||lamellipodium http://togogenome.org/gene/10090:Rgl1 ^@ http://purl.uniprot.org/uniprot/Q60695 ^@ Function|||Subunit ^@ Interacts with Ras.|||Probable guanine nucleotide exchange factor. http://togogenome.org/gene/10090:Or4c101 ^@ http://purl.uniprot.org/uniprot/A2AV10 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bpifb3 ^@ http://purl.uniprot.org/uniprot/Q80ZU7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||May have the capacity to recognize and bind specific classes of odorants. May act as a carrier molecule, transporting odorants across the mucus layer to access receptor sites. May serve as a primary defense mechanism by recognizing and removing potentially harmful odorants or pathogenic microorganisms from the mucosa or clearing excess odorant from mucus to enable new odorant stimuli to be received (By similarity).|||Secreted http://togogenome.org/gene/10090:Cyp2j11 ^@ http://purl.uniprot.org/uniprot/Q3UNV2|||http://purl.uniprot.org/uniprot/Q66JP5 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Zfp146 ^@ http://purl.uniprot.org/uniprot/Q8BQN6 ^@ Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds DNA. Interacts with SUMO conjugating enzyme UBC9/UBE2I. Interacts with the telomeric protein TERF2IP (By similarity).|||Expressed in heart, brain, liver, lung, skeletal muscle and kidney, and at much lower level in spleen and testicle. Expressed in lactating mammary gland.|||Mice lacking Zfp146 in mammary gland display impaired mammary gland development. They cannot sustain full growth of their pups. This phenotype is associated with an impaired mammary gland development noticeable only after mid-gestation.|||Nucleus http://togogenome.org/gene/10090:Megf9 ^@ http://purl.uniprot.org/uniprot/Q0VGR4|||http://purl.uniprot.org/uniprot/Q8BH27 ^@ Caution|||Subcellular Location Annotation ^@ It is uncertain whether Met-1 or Met-9 is the initiator.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Ovgp1 ^@ http://purl.uniprot.org/uniprot/Q62010 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 18 family.|||Binds to oocyte zona pellucida in vivo. May play a role in the fertilization process and/or early embryonic development.|||Epithelial cells of the oviduct.|||secretory vesicle http://togogenome.org/gene/10090:Trim54 ^@ http://purl.uniprot.org/uniprot/Q9ERP3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc expressed in the developing cardiac region. At 10.5 dpc expression is restricted to the cardiac region and myotome of the somites. Pre-natal expression is muscle-specific.|||Homooligomer and heterooligomer. Interacts with TRIM63 and probably with TRIM55 (By similarity). Interacts with tubulin.|||May bind and stabilize microtubules during myotubes formation.|||Selectively expressed in heart and skeletal muscle (at protein level). Also detected in lung and brain at much lower level.|||Z line|||cytoskeleton http://togogenome.org/gene/10090:Sp100 ^@ http://purl.uniprot.org/uniprot/O35892|||http://purl.uniprot.org/uniprot/Q3U876|||http://purl.uniprot.org/uniprot/Q6NTA3|||http://purl.uniprot.org/uniprot/Q8C405 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ By interferon.|||Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.|||Cytoplasm|||Homodimer. Interacts with members of the HP1 family of nonhistone chromosomal protein, such as CBX5 and CBX3 via the PxVxL motif. Interacts with ETS1; the interaction is direct and modulates ETS1 transcriptional activity. Interacts with the MRN complex which is composed of two heterodimers RAD50/MRE11 associated with a single NBN; recruits the complex to PML-related bodies. Interacts with HIPK2; positively regulates TP53-dependent transcription. Interacts with CASP8AP2; may negatively regulate CASP8AP2 export from the nucleus to the cytoplasm (By similarity).|||Nucleus|||PML body|||Sp100 is a single-copy gene. A related gene, D1LUB1/Sp100-rs, occurs in multiple copies and forms a conspicuous cluster in the chromosome 1. Sp100 and D1LUB1/Sp100-rs are homologous from the promoter up to a position in intron 3, but they differ 3' of that position.|||Sumoylated. Sumoylated with SUMO1. Sumoylation depends on a functional nuclear localization signal but is not necessary for nuclear import or nuclear body targeting. Sumoylation may stabilize the interaction with CBX5 (By similarity).|||The HSR domain is important for the nuclear body targeting as well as for the dimerization.|||Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. May also play a role in infection by viruses through mechanisms that may involve chromatin and/or transcriptional regulation (By similarity).|||nuclear body http://togogenome.org/gene/10090:Or5b107 ^@ http://purl.uniprot.org/uniprot/Q8VEV7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Eloa ^@ http://purl.uniprot.org/uniprot/Q8CB77 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A.|||Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit (By similarity). Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (By similarity). Interacts with ERCC6; the interaction is induced by DNA damaging agents or inhibitors of RNA polymerase II elongation (By similarity). Interacts (via BC-box) with CUL5 (By similarity).|||Nucleus|||SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).|||The BC-box, which mediates binding to the elongin BC complex, has the consensus sequence [APST]-L-x(3)-C-x(3)-[AILV]. http://togogenome.org/gene/10090:Vmn1r87 ^@ http://purl.uniprot.org/uniprot/Q8R255 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nom1 ^@ http://purl.uniprot.org/uniprot/Q3UFM5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC22 family.|||May interact with EIF4A1, EIF4A2 and EIF4A3. Interacts with PPP1CA and PPP1CC (By similarity).|||Plays a role in targeting PPP1CA to the nucleolus.|||nucleolus http://togogenome.org/gene/10090:Or4c29 ^@ http://purl.uniprot.org/uniprot/Q3SXJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Abcb6 ^@ http://purl.uniprot.org/uniprot/Q9DC29 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen (PubMed:27507172). May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress (PubMed:22294697, PubMed:17006453). May play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils (By similarity). In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin (By similarity). In addition may play a role in the transition metal homeostasis (By similarity).|||Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.|||Cell membrane|||Contains two independently folding units, the N-terminal transmembrane domain (residues 1-205) and the ABC-core domain (206-842) are respectively responsible for the lysosomal targeting and the ATPase activity.|||Early endosome membrane|||Endoplasmic reticulum membrane|||Endosome membrane|||Golgi apparatus membrane|||Highly expressed in embryonic liver.|||Homodimer.|||Homozygous knockout mice for Abcb6 gene appear phenotypically normal (PubMed:22294697). In a ferrochelatase-deficient mouse model where Abcb6 has been homozygously disrupted, mice exacerbate porphyria phenotypes shown by increased porphyrin accumulation, and marked liver injury (PubMed:27507172).|||Late endosome membrane|||Lysosome membrane|||Melanosome membrane|||Mitochondrion|||Mitochondrion outer membrane|||N-glycosylated.|||To date, the intracellular localization of ABCB6 is a matter of debate, with conflicting reports suggesting mitochondrial or endolysosomal localization, therefore questioning the requirement of ABCB6 in the mitochondrial import of porphyrins.|||Up-regulated during erythroid differentiation and heme biosynthesis (PubMed:17006453, PubMed:22294697). Up-regulated by cellular porphyrins (at protein level) (PubMed:17006453). Up-regulated in red blood cells under anemic condition (PubMed:22655043). Induced by sodium arsenite in a dose-dependent manner (PubMed:21266531).|||extracellular exosome|||multivesicular body membrane http://togogenome.org/gene/10090:Chrna6 ^@ http://purl.uniprot.org/uniprot/Q9R0W9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-6/CHRNA6 sub-subfamily.|||Cell membrane|||Neuronal AChR seems to be composed of two different types of subunits: alpha and non-alpha (beta). Interacts with LYPD6.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Cdyl ^@ http://purl.uniprot.org/uniprot/Q9WTK2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromatin reader protein that recognizes and binds histone H3 trimethylated at 'Lys-9', dimethylated at 'Lys-27' and trimethylated at 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3, respectively) (PubMed:12947414). Part of multimeric repressive chromatin complexes, where it is required for transmission and restoration of repressive histone marks, thereby preserving the epigenetic landscape (PubMed:12947414). Required for chromatin targeting and maximal enzymatic activity of Polycomb repressive complex 2 (PRC2); acts as a positive regulator of PRC2 activity by bridging the pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring nucleosomes (By similarity). Acts as a corepressor for REST by facilitating histone-lysine N-methyltransferase EHMT2 recruitment and H3K9 dimethylation at REST target genes for repression (By similarity). Involved in X chromosome inactivation in females: recruited to Xist RNA-coated X chromosome and facilitates propagation of H3K9me2 by anchoring EHMT2 (PubMed:24144980). Promotes EZH2 accumulation and H3K27me3 methylation at DNA double strand breaks (DSBs), thereby facilitating transcriptional repression at sites of DNA damage and homology-directed repair of DSBs (By similarity). Required for neuronal migration during brain development by repressing expression of RHOA (PubMed:28076783). By repressing the expression of SCN8A, contributes to the inhibition of intrinsic neuronal excitability and epileptogenesis (PubMed:28842554). In addition to acting as a chromatin reader, acts as a hydro-lyase (By similarity). Shows crotonyl-coA hydratase activity by mediating the conversion of crotonyl-CoA ((2E)-butenoyl-CoA) to beta-hydroxybutyryl-CoA (3-hydroxybutanoyl-CoA), thereby acting as a negative regulator of histone crotonylation (By similarity). Histone crotonylation is required during spermatogenesis; down-regulation of histone crotonylation by CDYL regulates the reactivation of sex chromosome-linked genes in round spermatids and histone replacement in elongating spermatids (PubMed:28803779). By regulating histone crotonylation and trimethylation of H3K27, may be involved in stress-induced depression-like behaviors, possibly by regulating VGF expression (PubMed:30665597). May have histone acetyltransferase activity; such activity is however unsure in vivo (PubMed:12072557).|||Chromosome|||Down-regulated upon neuronal activity in the hippocampus (PubMed:28842554). Up-regulated after social defeat stress (PubMed:30665597).|||Forms multimers and multimerization is required for stable binding to chromatin (By similarity). Interacts with HDAC1 and HDAC2 via its C-terminal acetyl-CoA-binding domain (PubMed:12947414). Interacts with EZH2, EED, SUZ12, REST, EHMT1 and EHMT2 (By similarity). Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2 (By similarity). Interacts with CHAF1A and CHAF1B; bridging the CAF-1 complex to the MCM2-7 (MCM) complex (By similarity). Interacts with MCM3 and MCM5; bridging the CAF-1 complex to the MCM2-7 (MCM) complex (By similarity). Interacts with EHMT2 and PRDM9; interaction only takes place when PRDM9 is bound to hotspot DNA (PubMed:27932493).|||Highly expressed in elongating spermatids during histone hyperacetylation.|||Highly expressed in testis (at protein level) (PubMed:10192397). Expressed in the hippocampus (at protein level) (PubMed:28842554). Expressed in the medial prefrontal cortex, prelimbic cortex, intralimbic cortex and cingulate cortex area (at protein level) (PubMed:30665597). Isoform 1: Expressed as 2 transcripts encoding the same protein, a ubiquitous transcript and a highly expressed testis-specific transcript (PubMed:10192397).|||Interaction with HDAC1 or HDAC2 prevents coenzyme A binding.|||Mice show no overt differences in body weight, but males display a substantial decrease in the size and weight of the testis and show reduced fertility. Males show decreased epididymal sperm counts, sperm cell motility, and sperm velocity and a marked increase in cell apoptosis in the testis.|||Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the presence of a N-terminal extension that inactivates the chromo domain.|||Nucleus|||The acetyl-CoA-binding domain mediates crotonyl-coA hydratase activity (By similarity). The acetyl-CoA-binding domain is required for recruitment to sites of DNA double strand breaks and for binding to poly (ADP ribose) moieties (By similarity).|||The chromo domain recognizes and binds histone H3K9me3, histone H3K27me2 and histone H3K27me3.|||Was initially reported to display histone acetyltransferase activity, with a preference for histone H4 (PubMed:12072557). Such activity is however unsure in vivo. Histone acetyltransferase activity would be in contradiction with the function of the protein in corepressor complexes (PubMed:12947414). Moreover, crystallographic studies in human demonstrated that it does not share any similarity with other acetyltransferases and instead forms a crotonase-like fold. http://togogenome.org/gene/10090:Cwc22 ^@ http://purl.uniprot.org/uniprot/Q8C5N3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC22 family.|||Component of the pre-catalytic spliceosome B and the catalytic spliceosome C complexes. Component of the minor spliceosome, which splices U12-type introns (By similarity). Interacts with EIF4A3 and PRPF19 in an RNA-independent manner. Direct interaction with EIF4A3 is mediated by the MIF4G domain. Full interaction with EIF4A3 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA.|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). Promotes exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Cdkn1b ^@ http://purl.uniprot.org/uniprot/P46414 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A peptide sequence containing only AA 28-79 retains substantial Kip1 cyclin A/CDK2 inhibitory activity.|||Belongs to the CDI family.|||Cytoplasm|||Endosome|||Forms a ternary complex composed of CCNE1, CDK2 and CDKN1B. Interacts directly with CCNE1; the interaction is inhibited by CDK2-dependent phosphorylation on Thr-187. Interacts with COPS5, subunit of the COP9 signalosome complex; the interaction leads to CDKN1B degradation. Interacts with NUP50; the interaction leads to nuclear import and degradation of phosphorylated CDKN1B. Interacts with CCND1 and SNX6 (By similarity). Interacts (Thr-197-phosphorylated form) with 14-3-3 proteins, binds strongly YWHAQ, weakly YWHAE and YWHAH, but not YWHAB nor YWHAZ; the interaction with YWHAQ results in translocation to the cytoplasm. Interacts with AKT1 and LYN; the interactions lead to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest. Forms a ternary complex with CCNA2 and CDK2; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements. Interacts (unphosphorylated form) with CDK2. Forms a complex with CDK2 and SPDYA, but does not directly interact with SPDYA. Forms a ternary complex composed of cyclin D, CDK4 and CDKN1B. Interacts (phosphorylated on Tyr-88 and Tyr-89) with CDK4; the interaction is required for cyclin D and CDK4 complex assembly, induces nuclear translocation and activates the CDK4 kinase activity. Interacts with GRB2. Interacts with PIM1. Identified in a complex with SKP1, SKP2 and CKS1B. Interacts with UHMK1; the interaction leads to cytoplasmic mislocation, phosphorylation of CDKN1B and inhibition of cell cycle arrest. Interacts also with CDK1. Dephosphorylated on Thr-187 by PPM1H, leading to CDKN1B stability (By similarity).|||Important regulator of cell cycle progression (PubMed:8033213, PubMed:12972555). Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (By similarity). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes (PubMed:8033213). Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.|||Nucleus|||Phosphorylated; phosphorylation occurs on serine, threonine and tyrosine residues. Phosphorylation on Ser-10 is the major site of phosphorylation in resting cells, takes place at the G(0)-G(1) phase and leads to protein stability. Phosphorylation on other sites is greatly enhanced by mitogens, growth factors, MYC and in certain cancer cell lines. The phosphorylated form found in the cytoplasm is inactivate. Phosphorylation on Thr-197 is required for interaction with 14-3-3 proteins. Phosphorylation on Thr-187, by CDK1 and CDK2 leads to protein ubiquitination and proteasomal degradation. Tyrosine phosphorylation promotes this process. Phosphorylation by PKB/AKT1 can be suppressed by LY294002, an inhibitor of the catalytic subunit of PI3K. Phosphorylation on Tyr-88 and Tyr-89 has no effect on binding CDK2, but is required for binding CDK4. Dephosphorylated on tyrosine residues by G-CSF (By similarity). Dephosphorylated on Thr-187 by PPM1H, leading to CDKN1B stability (By similarity).|||Subject to degradation in the lysosome. Interaction with SNX6 promotes lysosomal degradation.|||Ubiquitinated; in the cytoplasm by the KPC complex (composed of RNF123/KPC1 and UBAC1/KPC2) and, in the nucleus, by SCF(SKP2). The latter requires prior phosphorylation on Thr-187. Ubiquitinated; by a TRIM21-containing SCF(SKP2)-like complex; leads to its degradation (By similarity). http://togogenome.org/gene/10090:Septin7 ^@ http://purl.uniprot.org/uniprot/E9Q1G8|||http://purl.uniprot.org/uniprot/O55131 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cleavage furrow|||Coordinated expression with SEPTIN2 and SEPTIN6.|||Cytoplasm|||Expressed in the cerebral cortex (at protein level).|||Filament-forming cytoskeletal GTPase.|||Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Required for normal progress through mitosis. Involved in cytokinesis. Required for normal association of CENPE with the kinetochore. Plays a role in ciliogenesis and collective cell movements. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (By similarity).|||Midbody|||Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Filaments are assembled from asymmetrical heterotrimers, composed of SEPTIN2, SEPTIN6 and SEPTIN7 that associate head-to-head to form a hexameric unit. Within the trimer, directly interacts with SEPTIN6, while interaction with SEPTIN2 seems indirect. In the absence of SEPTIN6, forms homodimers. Interacts directly with CENPE and links CENPE to septin filaments composed of SEPTIN2, SEPTIN6 and SEPTIN7. Interacts with SEPTIN8, SEPTIN9 and SEPTIN11. Component of a septin core octameric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 and located in the sperm annulus; the SEPTIN12:SEPTIN7 association is mediated by the respective GTP-binding domains (By similarity). Interacts with SEPTIN2 and SEPTIN5 (PubMed:11739749).|||Septins polymerize into heterooligomeric protein complexes that form filaments.|||cilium axoneme|||flagellum|||kinetochore|||spindle http://togogenome.org/gene/10090:Niban2 ^@ http://purl.uniprot.org/uniprot/Q8R1F1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ As apoptosis proceeds, degraded via an proteasome-independent pathway, probably by caspases.|||Belongs to the Niban family.|||May play a role in apoptosis suppression.|||Membrane|||adherens junction|||cytosol http://togogenome.org/gene/10090:Hoxa7 ^@ http://purl.uniprot.org/uniprot/P02830 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Agbl5 ^@ http://purl.uniprot.org/uniprot/Q09M02 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins (PubMed:21074048, PubMed:20519502, PubMed:24022482, PubMed:26829768). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:21074048, PubMed:20519502, PubMed:24022482). Cleaves alpha- and gamma-linked polyglutamate tubulin side-chain, as well as the branching point glutamate (PubMed:21074048, PubMed:24022482). Also catalyzes the removal of alpha-linked glutamate residues from the carboxy-terminus of alpha-tubulin (PubMed:24022482). Mediates deglutamylation of nucleotidyltransferase CGAS, leading to CGAS antiviral defense response activation (PubMed:26829768).|||Mice are more vulnerable to DNA virus infection due to impaired immune response.|||Midbody|||Nucleus|||Widely expressed. Highly expressed in testis, and moderately in pituitary, brain, eye and kidney.|||cytosol|||spindle http://togogenome.org/gene/10090:Or8b12 ^@ http://purl.uniprot.org/uniprot/Q7TRE6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rassf9 ^@ http://purl.uniprot.org/uniprot/Q8K342 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endosome|||Interacts with PAM.|||May play a role in regulating vesicuar trafficking in cells. http://togogenome.org/gene/10090:Ddx46 ^@ http://purl.uniprot.org/uniprot/Q569Z5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX46/PRP5 subfamily.|||Cajal body|||Integral component of the 17S U2 snRNP.|||Membrane|||Nucleus speckle|||Plays an essential role in splicing, either prior to, or during A complex formation. http://togogenome.org/gene/10090:Gstm7 ^@ http://purl.uniprot.org/uniprot/Q80W21 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Cytoplasm|||Gstm7 is the putative homolog of human GSTM2.|||Homodimer. http://togogenome.org/gene/10090:Gm13285 ^@ http://purl.uniprot.org/uniprot/B1AYI3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Map6d1 ^@ http://purl.uniprot.org/uniprot/Q14BB9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STOP family.|||Expressed in brain. Found in neurons in primary cultures, but absent in glial cells.|||Golgi apparatus|||Interacts with calmodulin.|||May have microtubule-stabilizing activity.|||Palmitoylated. Palmitoylation enhances association with microtubules (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:B3gnt2 ^@ http://purl.uniprot.org/uniprot/Q3TVJ9|||http://purl.uniprot.org/uniprot/Q9Z222 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Catalyzes the initiation and elongation of poly-N-acetyllactosamine chains (PubMed:9892646). Probably constitutes the main polylactosamine synthase (PubMed:17890318).|||Expressed in heart, brain, lung, kidney and testis and, to a lesser extent, in liver and skeletal muscle. No expression in spleen.|||Golgi apparatus membrane|||Interacts with B3GNT8; this interaction greatly increases B3GNT2 catalytic activity, independently of B3GNT8 enzymatic activity.|||Membrane|||Strongly reduced number polylactosamine structures on N-glycans in immunological tissues. B-cells and T-cells proliferate show hyperproliferation (PubMed:17890318). Mice also display defective accessory olfactory bulb innervation (PubMed:23006775). Impaired sexual behaviour. While female mice are fertile, males show a reduced rate of reproduction. Defects cannot be attributed to any physical defect in their reproductive organs, suggesting that the phenotype observed may result from an impaired sexual response to female mating partners.|||There is some conflicting nomenclature, as some groups still name this protein B3gnt1 (PubMed:18008318). The correct and official nomenclature is however B3gnt2. http://togogenome.org/gene/10090:Nfx1 ^@ http://purl.uniprot.org/uniprot/B1AY10 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NFX1 family.|||Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Together with PABPC1 or PABPC4, acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination.|||Interacts with PABPC1 and PABPC4.|||Nucleus|||The RING-type zinc finger domain interacts with an ubiquitin-conjugating enzyme (E2) and facilitates ubiquitination.|||Ubiquitously expressed at 12 dpc and 14 dpc.|||Ubiquitously expressed, with highest levels in thymus. http://togogenome.org/gene/10090:Aldh1a2 ^@ http://purl.uniprot.org/uniprot/Q62148 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldehyde dehydrogenase family.|||Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively (PubMed:15911617, PubMed:8797830). Retinoate signaling is critical for the transcriptional control of many genes, for instance it is crucial for initiation of meiosis in both male and female (Probable). Recognizes retinal as substrate, both in its free form and when bound to cellular retinol-binding protein (By similarity). Lacks activity with benzaldehyde, acetaldehyde and octanal (PubMed:8797830). Displays complete lack of activity with citral (By similarity).|||Cytoplasm|||Expressed in the mesoderm adjacent to the node and primitive streak during early gastrulation (PubMed:9106168). At the headfold stage, mesodermal expression is restricted to posterior regions up to the base of the headfolds (PubMed:9106168). From 10.5 dpc onwards expressed within the spinal cord in cervical and lumbar regions adjacent to the developing limbs, as well as in specific regions of the developing head, including the tooth buds, inner ear, meninges and pituitary gland, and in several viscera (PubMed:9106168). Transiently expressed in the undifferentiated somites and the optic vesicles, and more persistently along the lateral walls of the intraembryonic coelom and around the hindgut diverticulum (PubMed:9106168).|||Homotetramer. http://togogenome.org/gene/10090:Gpr26 ^@ http://purl.uniprot.org/uniprot/Q0VBG4|||http://purl.uniprot.org/uniprot/Q8BZA7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 14.5 dpc, expression is limited to the developing nervous system with strong expression in the developing cortex, midbrain, cerebellum and medulla. Weaker expression is also detected in the trigeminal ganglion.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Exclusively expressed in the brain. Prominent expression is detected throughout the entire neocortex at all rostrocaudal and dorsoventral levels. Strong expression is detected in olfactory and auditory sensory areas.|||Membrane|||Orphan receptor. Displays a significant level of constitutive activity. Its effect is mediated by G(s)-alpha protein that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP (By similarity). http://togogenome.org/gene/10090:Usp38 ^@ http://purl.uniprot.org/uniprot/Q8BW70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Cytoplasm|||Deubiquitinating enzyme that plays a role in various cellular processes, including DNA repair, cell cycle regulation, and immune response (PubMed:27692986, PubMed:35238669). Plays a role in the inhibition of type I interferon signaling by mediating the 'Lys-33' to 'Lys-48' ubiquitination transition of TBK1 leading to its degradation. Cleaves the ubiquitin chain from the histone demethylase LSD1/KDM1A and prevents it from degradation by the 26S proteasome, thus maintaining LSD1 protein level in cells. Plays a role in the DNA damage response by regulating the deacetylase activity of HDAC1. Mechanistically, removes the 'Lys-63'-linked ubiquitin chain promoting the deacetylase activity of HDAC1 in response to DNA damage. Acts also as a specific deubiquitinase of histone deacetylase 3/HDAC3 and cleaves its 'Lys-63'-linked ubiquitin chains to lower its histone deacetylase activity. Regulates MYC levels and cell proliferation via antagonizing ubiquitin E3 ligase FBXW7 thereby preventing MYC 'Lys-48'-linked ubiquitination and degradation. Participates in antiviral response by removing both 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of Zika virus envelope protein E. Constitutively associated with IL-33R/IL1RL1, deconjugates its 'Lys-27'-linked polyubiquitination resulting in its autophagic degradation.|||Interacts with isoform 1 of FBXW7; this interaction prevents FBXW7-mediated degradation of MYC.|||Nucleus|||USP38-deletion mice produce higher levels of IFN-beta, TNF-alpha, and IL-6 than WT mice in response to viral infection (PubMed:27692986). They are also more susceptible to inflammatory damage and death and developed more serious pulmonary fibrosis after bleomycin treatment (PubMed:35238669). http://togogenome.org/gene/10090:Gcnt1 ^@ http://purl.uniprot.org/uniprot/Q09324 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 14 family.|||Deficient mice show normal organogenesis and fertility. The loss of core 2 O-glycans on leukocytes is associated with leukocytosis and impaired neutrophil recruitment at the inflammatory site, while lymphocyte homing to peripheral lymphoid organs is not affected.|||Expressed in kidney, liver, stomach, spleen, lung and brain.|||Glycosyltransferase that catalyzes the transfer of an N-acetylglucosamine (GlcNAc) moiety in beta1-6 linkage from UDP-GlcNAc onto mucin-type core 1 O-glycan to form the branched mucin-type core 2 O-glycan. The catalysis is metal ion-independent and occurs with inversion of the anomeric configuration of sugar donor (PubMed:9881978, PubMed:12954635, PubMed:22056345). Selectively involved in synthesis of mucin-type core 2 O-glycans that serve as scaffolds for the display of selectin ligand sialyl Lewis X epitope by myeloid cells, with an impact on homeostasis and recruitment to inflammatory sites (PubMed:9881978). Can also act on glycolipid substrates. Transfers GlcNAc moiety to GalGb4Cer globosides in a reaction step to the synthesis of stage-specific embryonic antigen 1 (SSEA-1) determinant (PubMed:7983056). Can use Galbeta1-3GalNAcalpha1-R and Galbeta1-3GalNAcbeta1-R oligosaccharide derivatives as acceptor substrates (PubMed:7983056).|||Golgi apparatus membrane|||Inactivated by thiol-reactive agents. Inhibited by free UDP.|||Interacts with GOLPH3; may control GCNT1 retention in the Golgi.|||N-glycosylated. http://togogenome.org/gene/10090:Tmem106b ^@ http://purl.uniprot.org/uniprot/Q80X71 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM106 family.|||Can form homomers (By similarity). Interacts (via N-terminus) with MAP6 (via C-terminus) (By similarity). Interacts (via C-terminus) with the vacuolar-type ATPase subunit ATP6AP1 (By similarity). Interacts (via N-terminus) with AP2M1 and CLTC (By similarity). Interacts with TMEM106C (By similarity).|||Cell membrane|||Expressed in the brain, in neurons (at protein level) (PubMed:25066864, PubMed:28728022, PubMed:29855382, PubMed:32160553, PubMed:32761777). Expressed in the spinal cord (at protein level) (PubMed:32160553).|||In neurons, involved in the transport of late endosomes/lysosomes (PubMed:25066864, PubMed:32160553). May be involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking (PubMed:25066864). May act as a molecular brake for retrograde transport of late endosomes/lysosomes, possibly via its interaction with MAP6 (By similarity). In motoneurons, may mediate the axonal transport of lysosomes and axonal sorting at the initial segment (PubMed:32160553). It remains unclear whether TMEM106B affects the transport of moving lysosomes in the anterograde or retrograde direction in neurites and whether it is particularly important in the sorting of lysosomes in axons or in dendrites (Probable). In neurons, may also play a role in the regulation of lysosomal size and responsiveness to stress (PubMed:25066864). Required for proper lysosomal acidification (PubMed:28728022).|||Knockout mice are born at the expected Mendelian ratio and young animals appear phenotypically normal (PubMed:28728022, PubMed:29855382, PubMed:32160553, PubMed:32852886). At 10 weeks of age, knockout mice develop proximal axonal swellings caused by drastically enlarged LAMP1-positive vacuoles (lysosomes/endosomes), increased retrograde axonal transport of lysosomes, and accumulation of lipofuscin and autophagosomes. Giant vacuoles specifically accumulate at the distal end and within the axon initial segment, but not in peripheral nerves or at axon terminals, resulting in an impaired facial-nerve-dependent motor performance (PubMed:32160553, PubMed:32852886). Using a different experimental approach to create the knockout, a more subtle, exclusively lysosomal phenotype is observed. At 2 months of age, numerous lysosomal proteins, including cathepsin B/CTSB, cathepsin L/CTSL, dipeptidyl peptidase 2/DPP7, LAMP1 and vacuolar-type ATPase subunits, are down-regulated and lysosomal acidification is impaired (PubMed:28728022). It has been suggested that these phenotypic differences might be due to incomplete knockout in animals with milder phenotypes (PubMed:32160553). Mice deficient in both PGRN and TMEM106B are born at normal Mendelian frequency and do not show any obvious growth defects or body weight changes. At around 3.5 months of age, the animals develop severe ataxia, hindlimb weakness, reduced motor activity, altered clasping behavior and eventually premature death. Neuronal loss and severe microglia and astrocyte activation are observed in the spinal cord, retina, and brain (PubMed:32761777, PubMed:32852886, PubMed:32929860). Myelin degeneration occurs in the spinal cord (PubMed:32761777). Drastic autophagy and lysosomal abnormalities, as well as other pathological changes related to frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis are observed (PubMed:32761777, PubMed:32852886, PubMed:32929860). Most studies consistently show that loss of TMEM106B exacerbates lysosome abnormalities found in GRN-single knockout animals, likely contributing to neuronal dysfunction and neuronal death (PubMed:32761777, PubMed:32852886, PubMed:32929860). However, one study reports that the expression levels of most lysosomal proteins are normalized in double knockout mice and comparable to those of wild-type animals and some behavioral phenotypes observed in GRN-single knockout mice, such as locomotor hyperactivity and disinhibition, are rescued in double knockout (PubMed:28728022). TMEM106B knockout does not rescue FTLD-like phenotypes in a mouse model mimicking the toxic gain-of-functions associated with overexpression of hexanucleotide repeat (GGGGCC) expansions in C9ORF72 (PubMed:29855382).|||Late endosome membrane|||Lysosome membrane http://togogenome.org/gene/10090:Nop16 ^@ http://purl.uniprot.org/uniprot/Q9CPT5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NOP16 family.|||nucleolus http://togogenome.org/gene/10090:Sap130 ^@ http://purl.uniprot.org/uniprot/A0A0R4J060|||http://purl.uniprot.org/uniprot/Q8BIH0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated.|||Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes (By similarity).|||Belongs to the SAP130 family.|||Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2 (By similarity). Interacts (released by dead or dying cells) with CLEC4E.|||Nucleus|||Sumoylated with SUMO1.|||The C-terminus may interact with HDAC-dependent and HDAC-independent corepressors.|||The N-terminus may interact with a transcriptional coactivator. http://togogenome.org/gene/10090:Or2ak7 ^@ http://purl.uniprot.org/uniprot/Q7TRZ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mapkbp1 ^@ http://purl.uniprot.org/uniprot/Q6NS57 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can form homodimers (via C-terminus). Interacts (via C-terminus) with WDR62 (via C-terminus). Interacts with MAPK9. Interacts (via N-terminus) with NOD2; the interaction is enhanced in presence of muramyl dipeptide (MDP) (By similarity). Interacts with MAPK10 (PubMed:10471813).|||Cytoplasm|||Negative regulator of NOD2 function. It down-regulates NOD2-induced processes such as activation of NF-kappa-B signaling, IL8 secretion and antibacterial response (By similarity). Involved in JNK signaling pathway (PubMed:10471813).|||Nucleus|||The N-terminal WD40 domain is necessary for the interaction with NOD2 and down-regulation of NOD2 function.|||Ubiquitously expressed. Highest expression observed in brain.|||spindle pole http://togogenome.org/gene/10090:Jmjd6 ^@ http://purl.uniprot.org/uniprot/Q9ERI5 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JMJD6 family.|||Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||Dioxygenase that can both act as a arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. Hydroxylates its own N-terminus, which is required for homooligomerization (By similarity). Plays a role in the regulation of nucleolar liquid-liquid phase separation (LLPS) by post-translationally modifying LIAT1 at its lysine-rich domain which inhibits LIAT1 nucleolar targeting (PubMed:33443146, PubMed:25369936). In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which preferentially demethylates asymmetric dimethylation. Demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), including mono-, symmetric di- and asymmetric dimethylated forms, thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. In collaboration with BRD4, interacts with the positive transcription elongation factor b (P-TEFb) complex in its active form to regulate polymerase II promoter-proximal pause release for transcriptional activation of a large cohort of genes. On distal enhancers, so called anti-pause enhancers, demethylates both histone H4R3me2 and the methyl cap of 7SKsnRNA leading to the dismissal of the 7SKsnRNA:HEXIM1 inhibitor complex. After removal of repressive marks, the complex BRD4:JMJD6 attract and retain the P-TEFb complex on chromatin, leading to its activation, promoter-proximal polymerase II pause release, and transcriptional activation. Demethylates other arginine methylated-proteins such as ESR1. Has no histone lysine demethylase activity (By similarity). Required for differentiation of multiple organs during embryogenesis (PubMed:15345036). Acts as a key regulator of hematopoietic differentiation: required for angiogenic sprouting by regulating the pre-mRNA splicing activity of U2AF2/U2AF65 (PubMed:21300889). Seems to be necessary for the regulation of macrophage cytokine responses (By similarity).|||Expressed early in development. Expressed from embryonic stem cells and throughout embryogenesis.|||Homooligomerizes; requires lysyl-hydroxylase activity (By similarity). Interacts with LUC7L2, LUC7L3 and U2AF2/U2AF65 (PubMed:21300889). Interacts with CDK9 and CCNT1; the interaction is direct with CDK9 and associates the P-TEFb complex when active. Interacts (via JmjC and N-terminal domains) with BRD4 (via NET domain); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers (By similarity).|||Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization.|||Mice display perinatal lethality, growth retardation, severe anemia and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. According to PubMed:14645847, mice are defective in removing apoptotic cells, especially in the lung and brain, in which dead cells accumulate, causing abnormal development and leading to neonatal lethality. According to PubMed:14715629, mice lacking Jmjd6 display a reduced number of macrophages and apoptotic cells in fetal liver. In contrast, according to PubMed:15345036, mice show a normal engulfment of apoptotic cells. The contradictory results concerning apoptosis and macrophage function may be explained by the fact that the protein plays a key role in hematopoietic differentiation.|||The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus.|||Was initially thought to constitute the phosphatidylserine receptor, a receptor that mediates recognition of phosphatidylserine, a specific marker only present at the surface of apoptotic cells. Phosphatidylserine receptor probably participates in apoptotic cell phagocytosis. This protein was identified using phage display expressing mAb 217, an antibody that specifically recognizes phosphatidylserine receptor. However, its nuclear localization and the fact that mAb 217 antibody still recognizes the phosphatidylserine receptor in mice lacking Jmjd6, strongly suggest that it does not constitute the receptor for phosphatidylserine and is not involved in apoptotic cell removal.|||Widely expressed. Expressed in brain, eye, spinal chord, thymus, lung, liver, kidney and intestine.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Rrm2b ^@ http://purl.uniprot.org/uniprot/Q6PEE3 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ribonucleoside diphosphate reductase small chain family.|||Binds 2 iron ions per subunit.|||Cytoplasm|||Heterotetramer with large (RRM1) subunit. Interacts with p53/TP53. Interacts with RRM1 in response to DNA damage (By similarity).|||Mice develop normally until they are weaned but from then on exhibit growth retardation and early mortality. Pathological examination indicates that multiple organs fail and that they die from severe renal failure by the age of 14 weeks.|||Nucleus|||Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage. http://togogenome.org/gene/10090:Glo1 ^@ http://purl.uniprot.org/uniprot/A5GZX3|||http://purl.uniprot.org/uniprot/Q9CPU0 ^@ Activity Regulation|||Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subunit ^@ Belongs to the glyoxalase I family.|||Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are bound between subunits.|||Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione (PubMed:18695250). Involved in the regulation of TNF-induced transcriptional activity of NF-kappa-B (By similarity). Required for normal osteoclastogenesis (PubMed:18695250).|||Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.|||Exists in a nitric oxide (NO)-modified form. The exact nature of the modification is unknown, but it suppresses the TNF-induced transcriptional activity of NF-kappa-B (By similarity).|||Expressed at higher levels in CD-1 mice which have been bred for low-anxiety-related behavior than in those which have been bred for high-anxiety-related behavior.|||Glutathionylation at Cys-139 inhibits enzyme activity.|||Homodimer.|||Phosphorylated at Thr-107 in the presence of CaMK2. However, this is a consensus site for phosphorylation by CK2 so phosphorylation may be mediated by CK2 rather than CaMK2. Phosphorylation is induced by TNF and suppresses the TNF-induced transcriptional activity of NF-kappa-B (By similarity).|||Subject to competitive inhibition by methyl-gerfelin. http://togogenome.org/gene/10090:Gfra4 ^@ http://purl.uniprot.org/uniprot/A2AP45|||http://purl.uniprot.org/uniprot/Q9JJT2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alternative N-terminal. Probably non-functional.|||Belongs to the GDNFR family.|||Cell membrane|||Expressed in many tissues including adrenal medulla, brain neurons, with highest levels in the cerebral cortex and hippocampus. Moderate levels found in the gut circular muscle and myenteric ganglia as well as in other peripheral ganglia, including the sensory dorsal root and trigeminal as well as superior cervical and sympathetic chain ganglia. Isoform a1, isoform a2, isoform b1 and isoform b2 are exclusively found in the thyroid, parthyroid and pituitary glands.|||Expressed in several tissues at different embryonic and postnatal stages such as the condensing mesenchyme of developing bones and developing nervous system. Expressed in the developing pituitary gland from 16 dpc and in developing thyroid C-cells from 14 dpc. In the ventral spinal cord, levels decline before birth. In the parathyroid, levels first detected in 3- to 6-week-old mice with high expression. In the adrenal medulla, expressed only in newborn, postnatal (P08) and adult mice. Isoform a1 and isoform b1 are prefentially expressed in 3-week-old thyroid, isoform a2 and isoform b2 in newborn and 6-week-old thyroid glands as well as in postnatal adrenal and pituitary glands.|||Interacts with SORL1.|||Receptor for persephin. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. May be important in C-cell development and, in the postnatal development of the adrenal medulla.|||Secreted http://togogenome.org/gene/10090:Ice2 ^@ http://purl.uniprot.org/uniprot/Q3UZ18 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ICE2 family.|||Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III.|||Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts with ICE1 (via C-terminus domain). Interacts with ELL (By similarity).|||Down-regulated during neuronal differentiation, probably by NMDA receptor.|||Expressed in brain from 13 dpc to P0, and down-regulated after birth.|||Expressed in brain, kidney, liver and testis.|||Nucleus http://togogenome.org/gene/10090:Wdr75 ^@ http://purl.uniprot.org/uniprot/Q3U821 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the proposed t-UTP subcomplex of the ribosomal small subunit (SSU) processome. SSU processome is composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Ribosome biogenesis factor. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I.|||nucleolus http://togogenome.org/gene/10090:Or3a1 ^@ http://purl.uniprot.org/uniprot/Q8VFX7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4a39 ^@ http://purl.uniprot.org/uniprot/Q8VG59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dlgap5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0G7|||http://purl.uniprot.org/uniprot/Q8K4R9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAPAP family.|||Cytoplasm|||Decreased phosphorylation levels are associated with the differentiation of intestinal epithelial cells.|||Expressed at low levels in normal resting liver. Up-regulated in regenerating liver after partial hepatectomy.|||Interacts with CDC2. Interacts with the C-terminal proline-rich region of FBXO7. Recruited by FBXO7 to a SCF (SKP1-CUL1-F-box) protein complex in a CDC2/Cyclin B-phosphorylation dependent manner. Interacts with CDH1 (By similarity).|||Nucleus|||Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells. Mitotic phosphoprotein regulated by the ubiquitin-proteasome pathway. Key regulator of adherens junction integrity and differentiation that may be involved in CDH1-mediated adhesion and signaling in epithelial cells (By similarity).|||Ubiquitinated, leading to its degradation.|||spindle http://togogenome.org/gene/10090:Vmn1r177 ^@ http://purl.uniprot.org/uniprot/E9PXM3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcm1 ^@ http://purl.uniprot.org/uniprot/Q9R0L6 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PCM1 family.|||Cytoplasmic granule|||Expressed in the hippocampus and dentate gyrus, the columnar epithelial cells of bronchioles, the olfactory epithelium, the pericardium and the inner segment of the retina.|||Maternally derived during fertilization. Expressed in the pericardium of the developing embryo and in the epidermal layer surrounding the digits.|||Phosphorylated on multiple serine and threonine residues by DYRK3 during the G2-to-M transition, after the nuclear-envelope breakdown. Phosphorylation by DYRK3 promotes disassembly of pericentriolar material (By similarity). Phosphorylation at Ser-372 mediated by PLK4 is required to maintain the integrity of centriolar satellites (By similarity).|||Required for centrosome assembly and function (PubMed:12112146). Essential for the correct localization of several centrosomal proteins including CEP250, CETN3, PCNT and NEK2 (By similarity). Required to anchor microtubules to the centrosome (By similarity). Also involved in cilium biogenesis by recruiting the BBSome, a ciliary protein complex involved in cilium biogenesis, to the centriolar satellites (PubMed:27979967). Recruits the tubulin polyglutamylase complex (TPGC) to centriolar satellites (By similarity).|||Self-associates. Interacts with BBS4, BBS8, CETN3, HAP1, NDE1, NDEL1, MAP1LC3B, GABARAPAL2, and GABARAP. Interacts with CEP131; the interaction increases in response to ultraviolet light (UV) radiation. Associates with microtubule; association to microtubule is reduced in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, in a process that requires p38 MAP kinase signaling (By similarity). Interacts with C2CD3 (PubMed:24469809). Interacts with CCDC113 (By similarity). Interacts with SSX2IP (PubMed:24356449). Interacts with CCDC13 (By similarity). Interacts with CEP290 (PubMed:17705300). Interacts with PARD6A (By similarity). Interacts with KIAA0753/OFIP, CEP20/FOR20 and OFD1; the interaction with CEP20/FOR20 and OFD1 may be mediated by KIAA0753/OFIP (PubMed:26643951). Interacts with CCDC66 (By similarity). Interacts with CCDC61 (By similarity). Interacts with DZIP1; localizes DZIP1 and the associated BBSome to centriolar satellite (PubMed:27979967). Interacts with CSTPP1, TTLL1, TPGS1 and LRRC49 (By similarity).|||Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3 ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia formation. Monoubiquitination by MIB1 is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, resulting in cilia formation initiation.|||centriolar satellite|||centrosome|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Dclre1c ^@ http://purl.uniprot.org/uniprot/Q32MX8|||http://purl.uniprot.org/uniprot/Q8K4J0 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.|||Interacts with ATM, BRCA1, PRKDC and TP53BP1. Also exhibits ATM- and phosphorylation-dependent interaction with the MRN complex, composed of MRE11, RAD50, and NBN (By similarity).|||May be due to an intron retention.|||Nucleus|||Phosphorylation on undefined residues by PRKDC may stimulate endonucleolytic activity on 5' and 3' hairpins and overhangs. PRKDC must remain present, even after phosphorylation, for efficient hairpin opening. Also phosphorylated by ATM in response to ionizing radiation (IR) and by ATR in response to ultraviolet (UV) radiation (By similarity).|||Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein likely exhibits single-strand specific 5'-3' exonuclease activity in isolation, and may acquire endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity may be required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ. http://togogenome.org/gene/10090:Fbn1 ^@ http://purl.uniprot.org/uniprot/Q61554 ^@ Biotechnology|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adipokine secreted by white adipose tissue that plays an important regulatory role in the glucose metabolism of liver, muscle and pancreas (PubMed:31230984, PubMed:30997682). Hormone that targets the liver in response to fasting to increase plasma glucose levels (PubMed:31230984). Binds the olfactory receptor Olfr734 at the surface of hepatocytes and promotes hepatocyte glucose release by activating the protein kinase A activity in the liver, resulting in rapid glucose release into the circulation (PubMed:31230984). May act as a regulator of adaptive thermogenesis by inhibiting browning and energy consumption, while increasing lipid deposition in white adipose tissue (PubMed:33705351). Also acts as an orexigenic hormone that increases appetite: crosses the blood brain barrier and exerts effects on the hypothalamus (PubMed:29106398). In the arcuate nucleus of the hypothalamus, asprosin directly activates orexigenic AgRP neurons and indirectly inhibits anorexigenic POMC neurons, resulting in appetite stimulation (PubMed:29106398, PubMed:32337066). Activates orexigenic AgRP neurons via binding to the olfactory receptor Olfr734 (PubMed:32337066). May also play a role in sperm motility in testis via interaction with Olfr734 receptor (PubMed:31798959).|||Attractive therapeutic target for type II diabetes and metabolic syndrome (PubMed:33904407). Inactivation by monoclonal antibodies that recognize unique Asprosin epitopes reduces appetite, body weight and blood glucose levels in mice with metabolic syndrome, leading to mitigate metabolic syndrome (PubMed:33904407).|||Belongs to the fibrillin family.|||Cleavage of N- and C-terminus by furin is required for incorporation into the extracellular matrix and assembly into microfibrils. The C-terminus, which corresponds to the Asprosin chain, was initially thought to constitute a propeptide. Fibrillin-1 and Asprosin chains are still linked together during the secretion from cells, but are subsequently separated by furin, an essential step for incorporation of Fibrillin-1 into the nascent microfibrils.|||Displays circadian oscillation with an acute decrease in levels coinciding with the onset of feeding (at protein level) (PubMed:27087445).|||Forms intermolecular disulfide bonds either with other fibrillin-1 molecules or with other components of the microfibrils.|||Interacts with COL16A1. Interacts with integrin alpha-V/beta-3. Interacts with ADAMTS10; this interaction promotes microfibril assembly (By similarity). Interacts with THSD4; this interaction promotes fibril formation (PubMed:19940141). Interacts (via N-terminal domain) with FBLN2 and FBLN5. Interacts with ELN. Forms a ternary complex with ELN and FBLN2 or FBLN5 and a significant interaction with ELN seen only in the presence of FBLN2 or FBLN5. Interacts (via N-terminal domain) with LTBP2 (via C-terminal domain) in a Ca(+2)-dependent manner. Interacts (via N-terminal domain) with LTBP1 (via C-terminal domain). Interacts with integrins ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB6. Interacts (via N-terminal domain) with BMP2, BMP4, BMP7, BMP10 and GDF5. Interacts (via N-terminal domain) with MFAP2 and MFAP5. Interacts with ADAMTSL5. Interacts with MFAP4. Interacts (via N-terminal domain) with TNFSF11 in a Ca(+2)-dependent manner (By similarity). Interacts (via N-terminal domain) with EFEMP2; this interaction inhibits EFEMP2 binding to LOX and ELN (By similarity).|||Mice lacking Asprosin show low appetite, reduced adiposity and protection from diet-induced obesity.|||Neonatal lethality due to ruptured aortic aneurysm, impaired pulmonary function and/or diaphragmatic collapse. Neonatal aorta show a disorganized and poorly developed medial layer but normal levels of elastin cross-links.|||O-glycosylated on serine residues by POGLUT2 and POGLUT3 which is necessary for efficient protein secretion.|||Secreted|||Secreted by white adipose tissue (at protein level).|||Strongly expressed during the first week of osteoblast differentiation.|||Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues. Fibrillin-1-containing microfibrils provide long-term force bearing structural support. In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin. In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus where they provide tensile strength and have anchoring roles. Fibrillin-1 also plays a key role in tissue homeostasis through specific interactions with growth factors, such as the bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and latent transforming growth factor-beta-binding proteins (LTBPs), cell-surface integrins and other extracellular matrix protein and proteoglycan components (By similarity). Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (PubMed:20855508). Negatively regulates osteoclastogenesis by binding and sequestering an osteoclast differentiation and activation factor TNFSF11. This leads to disruption of TNFSF11-induced Ca(2+) signaling and impairment of TNFSF11-mediated nuclear translocation and activation of transcription factor NFATC1 which regulates genes important for osteoclast differentiation and function (PubMed:24039232). Mediates cell adhesion via its binding to cell surface receptors integrins ITGAV:ITGB3 and ITGA5:ITGB1. Binds heparin and this interaction plays an important role in the assembly of microfibrils (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Fam83f ^@ http://purl.uniprot.org/uniprot/A0A0R4J033|||http://purl.uniprot.org/uniprot/Q3UKU4 ^@ Sequence Caution|||Similarity ^@ Belongs to the FAM83 family.|||Probable cloning artifact. http://togogenome.org/gene/10090:Gtf3c2 ^@ http://purl.uniprot.org/uniprot/Q8BL74 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Intron retention.|||Nucleus|||Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6.|||Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. May play a direct role in stabilizing interactions of TFIIIC2 with TFIIIC1 (By similarity). http://togogenome.org/gene/10090:Or11g1 ^@ http://purl.uniprot.org/uniprot/L7N1X7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4d5 ^@ http://purl.uniprot.org/uniprot/Q8VFN1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Isg15 ^@ http://purl.uniprot.org/uniprot/Q64339 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein.|||By type I interferons.|||Cytoplasm|||Homodimer; disulfide-linked (By similarity). Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) (By similarity). Interacts with NEDD4 (By similarity).|||Induced as an inactive, precursor protein that is cleaved by specific proteases to expose the C-terminal diglycine (LRLRGG) motif. This motif is essential not only for its conjugation to substrates but also for its recognition by the relevant processing proteases (By similarity).|||S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins.|||Secreted|||Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, TRIM25, STAT5A, MAPK1/ERK2 and globin. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses. Can also isgylate: RIGI which inhibits its function in antiviral signaling response, IRF3 which inhibits its ubiquitination and degradation as well as EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A and B virus, sindbis virus (SV) and herpes simplex type-1 (HHV-1). Plays a significant role in the control of neonatal Chikungunya virus (CHIKV) infection by acting as a putative immunomodulator of pro-inflammatory cytokines. Protects mice against the consequences of Chikungunya virus infection by down-regulating the pathogenic cytokine response, often denoted as the cytokine storm. Plays a role in erythroid differentiation. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (By similarity). http://togogenome.org/gene/10090:Rcbtb2 ^@ http://purl.uniprot.org/uniprot/Q99LJ7 ^@ Developmental Stage|||Domain|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in testis and heart (at protein level).|||Expressed in testis from postnatal day 12 onwards, reaching maximal levels at postnatal day 30 (at protein level).|||The BTB domain might play a role in targeting to acrosomal vesicles.|||acrosome http://togogenome.org/gene/10090:Eqtn ^@ http://purl.uniprot.org/uniprot/Q9D9V2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acrosomal membrane-anchored protein involved in the process of fertilization and in acrosome biogenesis.|||Cytoplasm|||Highly N- and O-glycosylated; contains sialic acid. MN9 epitope is O-glycosylated.|||Interacts with SNAP25.|||Nucleus|||Sperm specific, including germ cells (at protein level).|||acrosome inner membrane|||acrosome membrane|||acrosome outer membrane http://togogenome.org/gene/10090:Akr1c6 ^@ http://purl.uniprot.org/uniprot/P70694|||http://purl.uniprot.org/uniprot/Q3UEM0 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Active toward androgens, estrogens, and xenobiotic substrates. Also exhibits low 20 alpha-HSD activity. Shows a-stereospecificity in hydrogen transfer between cofactors and substrates (A-specific). Preferentially catalyzes the reduction of 4-androstenedione, 5-alpha-androstane-3,17-dione, androsterone and dehydroepiandrosterone to testosterone, dihydrotestosterone, 5-alpha-androstane-3-alpha,17-beta-diol and 5-androstene-3-beta,17-beta-diol, respectively.|||Belongs to the aldo/keto reductase family.|||Mainly found in liver. Also expressed weakly in kidney.|||Monomer.|||Three forms are detected, probably due to post-translational modifications. http://togogenome.org/gene/10090:Gna15 ^@ http://purl.uniprot.org/uniprot/P30678 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the G-alpha family. G(q) subfamily.|||Expressed primarily in hematopoietic cells. Coexpressed with EDG6 at the same relative levels in all tissues examined, with the highest levels in adult spleen and lung.|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. http://togogenome.org/gene/10090:Or5ac15 ^@ http://purl.uniprot.org/uniprot/L7N1Y8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Syn3 ^@ http://purl.uniprot.org/uniprot/D3Z620|||http://purl.uniprot.org/uniprot/Q3KN99|||http://purl.uniprot.org/uniprot/Q8JZP2 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synapsin family.|||Interacts with CAPON.|||May be involved in the regulation of neurotransmitter release and synaptogenesis. Binds ATP with high affinity and ADP with a lower affinity. This is consistent with a catalytic role of the C-domain in which ADP would be dissociated by cellular ATP after bound ATP was hydrolyzed (By similarity).|||Phosphorylation at Ser-9 dissociates synapsins from synaptic vesicles.|||Regulated by calcium. Calcium inhibits ATP binding to the C-domain (By similarity).|||The A region binds phospholipids with a preference for negatively charged species.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Cul1 ^@ http://purl.uniprot.org/uniprot/Q9WTX6 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ (Microbial infection) Deneddylated by murine cytomegalovirus M48 leading to a S-phase-like environment that is required for efficient replication of the viral genome.|||(Microbial infection) Interacts with murine cytomegalovirus M48.|||Belongs to the cullin family.|||Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit (PubMed:10097128, PubMed:12140560, PubMed:16880526, PubMed:23452855, PubMed:23452856). Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44 (By similarity). Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC (PubMed:10097128, PubMed:11735228). This complex binds phosphorylated NFKBIA (PubMed:10097128). Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF (By similarity). Interacts with CCNF (By similarity). Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate (By similarity). Interacts with FBXW8 (PubMed:16880526). Interacts with RNF7 (By similarity). Interacts with CUL7; the interaction seems to be mediated by FBXW8 (PubMed:16880526). Interacts with TRIM21 (By similarity). Interacts with COPS2 (PubMed:11967155). Interacts with DCUN1D1 and UBE2M. Interacts with DCUN1D3. Interacts with DCUN1D4 (By similarity). Identified in a complex with RBX1 and GLMN (By similarity). Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. Interacts with COPS9. Interacts with UBXN1 (By similarity). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (PubMed:23319590). Interacts with NOTCH2 (By similarity). Part of a complex that contains DCUN1D5, CUL1 and RBX1; this interaction is bridged by CUL1 (By similarity). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (By similarity).|||Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2.|||Embryo fibroblasts and embryo preadipocytes.|||Neddylated; which enhances the ubiquitination activity of SCF. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. http://togogenome.org/gene/10090:Cyp2c54 ^@ http://purl.uniprot.org/uniprot/Q6XVG2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in liver.|||Metabolizes arachidonic acid mainly to 12-hydroxyeicosatetraenoic acid (HETE).|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Gas2l2 ^@ http://purl.uniprot.org/uniprot/Q5SSG4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GAS2 family.|||Cell membrane|||Expressed in tracheal epithelial cells (at protein level).|||Interacts with ADORA2A (via its cytoplasmic C-terminal domain) (PubMed:23994616). Interacts with GNAS, GNAL, GNAQ, and GNA13 (PubMed:23994616). Interacts with MAPRE1 (PubMed:24706950).|||Involved in the cross-linking of microtubules and microfilaments (By similarity). Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers (By similarity). Enhances ADORA2-mediated adenylyl cyclase activation by acting as a scaffold to recruit trimeric G-protein complexes to ADORA2A (PubMed:23994616). Regulates ciliary orientation and performance in cells located in the airway (PubMed:30665704).|||Knockout mice exhibit a high rate of neonatal death (PubMed:30665704). Mice that survive show signs of hydrocephalus at postnatal days 14 and 21, along with mucus accumulation in multiple sinuses, and remodeling of the nasal cavity (PubMed:30665704). Conditional knockout in tracheal cells lead to isolated cases of hydrocephalus, as well as chronic rhinosinusitis and accumulation of mucus in the nasal cavity, which is caused by impaired mucociliary clearance (PubMed:30665704).|||cilium basal body|||cytoskeleton|||stress fiber http://togogenome.org/gene/10090:Or1f12 ^@ http://purl.uniprot.org/uniprot/A0A1W2P740 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnaset2b ^@ http://purl.uniprot.org/uniprot/C0HKG5|||http://purl.uniprot.org/uniprot/C0HKG6|||http://purl.uniprot.org/uniprot/Q5FWA0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RNase T2 family.|||Endoplasmic reticulum lumen|||Inhibited by Zn(2+) and Cu(2+).|||Lysosome lumen|||Mitochondrion intermembrane space|||Ribonuclease that plays an essential role in innate immune response by recognizing and degrading RNAs from microbial pathogens that are subsequently sensed by TLR8. Cleaves preferentially single-stranded RNA molecules between purine and uridine residues, which critically contributes to the supply of catabolic uridine and the generation of purine-2',3'-cyclophosphate-terminated oligoribonucleotides. In turn, RNase T2 degradation products promote the RNA-dependent activation of TLR8. Also plays a key role in degradation of mitochondrial RNA and processing of non-coding RNA imported from the cytosol into mitochondria. Participates as well in degradation of mitochondrion-associated cytosolic rRNAs.|||Secreted http://togogenome.org/gene/10090:Vmn1r185 ^@ http://purl.uniprot.org/uniprot/Q8R299 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Oaf ^@ http://purl.uniprot.org/uniprot/Q8QZR4 ^@ Similarity ^@ Belongs to the OAF family. http://togogenome.org/gene/10090:Nr2e3 ^@ http://purl.uniprot.org/uniprot/Q543C7|||http://purl.uniprot.org/uniprot/Q9QXZ7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Defects in Nr2e3 are the cause of the retinal degeneration type 7 (Rd7) phenotype characterized by excessive blue cones and loss of rods.|||Di- and tri-sumoylated in developing retina. PIAS3-mediated sumoylation promotes repression of cone-specific gene expression and activation of rod-specific genes. Sumoylation on Lys-178 appears to be the main site.|||Expression found as early as 18 dpc in developing retina. From P3 to P6, expression increases in developing rods. Expression, thereafter, in the future inner nuclear layer migrating to the final destination of the outer nuclear layer. In the mature retina, exclusively expressed in rods.|||Homodimer. Interacts with PIAS3; the interaction sumoylates NR2E3 and promotes repression of cone-specific gene transcription and activation of rod-specific genes. Component of a rod photoreceptor complex that includes NR2E3, PIAS3, NRL, CRX and/or NR1D1. Binds directly in the complex with CRX, PIAS3 and NR1D1 (By similarity). Interacts (via the DNA-binding domain) with CRX (via its DNA binding domain); the interaction represses S- and M-cone opsin expression.|||Nucleus|||Orphan nuclear receptor of retinal photoreceptor cells. Transcriptional factor that is an activator of rod development and repressor of cone development. Binds the promoter region of a number of rod- and cone-specific genes, including rhodopsin, M- and S-opsin and rod-specific phosphodiesterase beta subunit. Enhances rhodopsin expression. Represses M- and S-cone opsin expression.|||Retina. Rod-specific. Expressed in the outer nuclear lyer of the mature retina. http://togogenome.org/gene/10090:Ncmap ^@ http://purl.uniprot.org/uniprot/Q99JS0 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in sciatic nerve and placenta at 15.5 dpc.|||Found in the peripheral nervous system (PNS) Schwann cells (at protein level). Expressed in the PNS, primarily limited to Schwann cells.|||Glycosylated.|||Plays a role in myelin formation.|||Up-regulated in Schwann cells by EGR2 during nerve development and after nerve injury. http://togogenome.org/gene/10090:Fcho1 ^@ http://purl.uniprot.org/uniprot/Q8K285 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FCHO family.|||Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. May regulate Bmp signaling by regulating clathrin-mediated endocytosis of Bmp receptors. Involved in the regulation of T-cell poliferation and activation. Affects TCR clustering upon receptor triggering and modulates its internalisation, playing a role in TCR-dependent T-cell activation.|||Mainly detected in brain and spleen.|||May oligomerize and form homotetramer (PubMed:21762413). Interacts with AP2A2 and AP2B1; 2 subunits of the adaptor protein complex AP-2 (PubMed:22484487). Interacts with DAB2. Interacts with clathrin (CLTC or CLTCL1). Interacts with EPS15, EPS15R and ITSN1. Interacts with AGFG1 and CALM. May interact with ACVR1; linking this receptor to clathrin-mediated endocytosis (By similarity).|||clathrin-coated pit http://togogenome.org/gene/10090:Iqsec1 ^@ http://purl.uniprot.org/uniprot/A0A1D5RM83|||http://purl.uniprot.org/uniprot/E9PUA3|||http://purl.uniprot.org/uniprot/Q8R0S2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BRAG family.|||Cytoplasm|||Expressed in hippocampus.|||Expression is first detected at postanatal day P7 and increases until P42 (at protein level).|||Guanine nucleotide exchange factor for ARF1 and ARF6. Guanine nucleotide exchange factor activity is enhanced by lipid binding. Accelerates GTP binding by ARFs of all three classes. Guanine nucleotide exchange protein for ARF6, mediating internalization of beta-1 integrin (By similarity). Involved in neuronal development (PubMed:31607425). In neurons, plays a role in the control of vesicle formation by endocytoc cargo. Upon long term depression, interacts with GRIA2 and mediates the activation of ARF6 to internalize synaptic AMPAR receptors (By similarity).|||Interacts with ARF1 and ARF6. Interacts with GRIA2; the interaction is required for ARF6 activation.|||Mice with a conditional knockout in cortical neurons exhibit an increased density of dendritic spines with an immature morphology.|||Nucleus|||Postsynaptic density|||The PH domain mediates interaction with lipid membranes that contain phosphatidylinositol-4,5-bisphosphate, but does not bind membranes that lack phosphatidylinositol-4,5-bisphosphate.|||synaptic vesicle http://togogenome.org/gene/10090:Igfbp2 ^@ http://purl.uniprot.org/uniprot/D3YU40|||http://purl.uniprot.org/uniprot/P47877 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds IGF2 more than IGF1.|||Expressed embryos at day 11.5. Also expressed in fetal livers with expression increasing dramatically after birth. Expression decreases only slightly after postnatal day 3 and remains abundant thereafter.|||Highly expressed in adult liver, but also in kidney, lung, brain, spleen, testis and ovary.|||Inhibits IGF-mediated growth and developmental rates (By similarity). IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||O-glycosylated.|||Secreted|||The C-terminus is required for IGF-binding and growth inhibition. http://togogenome.org/gene/10090:Slc35d1 ^@ http://purl.uniprot.org/uniprot/A2AKQ0 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Antiporter that transports nucleotide sugars across the endoplasmic reticulum (ER) membrane in exchange for either their cognate nucleoside monophosphate or another nucleotide sugar (By similarity). Transports various UDP-sugars including UDP-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc), UDP-N-acetyl-alpha-D-galactosamine (UDP-GalNAc) and UDP-alpha-D-glucuronate (UDP-GlcA), which are used by ER glucosyltransferases as sugar donors for the synthesis of sugar chains of glycoproteins, glycolipids and oligosaccharides (By similarity). May couple UDP-GlcNAc or UDP-GalNAc efflux to UDP-GlcA influx into the ER lumen that in turn stimulates glucuronidation and subsequent excretion of endobiotics and xenobiotics (By similarity). Plays a role in chondroitin sulfate biosynthesis, which is important for formation of cartilage extracellular matrix and normal skeletal development.|||Belongs to the TPT transporter family. SLC35D subfamily.|||Endoplasmic reticulum membrane|||It is uncertain whether Met-1 or Met-31 is the initiator.|||Neonatal lethality. Skeletal development is severely impaired leading to reduced snout and body length, and extremely short limbs. The proliferating zone of epiphyseal cartilage is disorganized with densely packed round chondrocytes and little extracellular matrix, in contrast to the regular columnar organization of chondrocytes in wild type cartilage. Chondroitin sulfate content of cartilage is significantly reduced, associated with reduced proteoglycan aggregates in the extracellular matrix. http://togogenome.org/gene/10090:Hipk1 ^@ http://purl.uniprot.org/uniprot/O88904 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.|||Cytoplasm|||Highest at 12 dpc, where it is expressed primarily in the central nervous system. Highly induced during primary fetal liver erythropoiesis. Expressed in the inner retina during late embryogenesis, predominantly in cytoplasm.|||Interacts with Nkx1-2, Nkx2-5, MYB, PARK7, DAXX and p53/TP53. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF. This complex formation promotes MAP3K5-JNK activation and subsequent apoptosis.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Nucleus speckle|||Phosphorylated and activated by JNK1 (By similarity). Autophosphorylated.|||Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (By similarity).|||Small eyes with deficient lens, abnormal retinal lamination, and thickened retinas.|||Sumoylated. When conjugated it is directed to nuclear speckles. SENP1-mediated desumoylation is mediated by TNF in response to stress stimuli, triggering transient translocation from nucleus to cytoplasm.|||Ubiquitously expressed, with high levels in reproductive tissues. Expressed in the epithelial layer of mammary gland, uterus and epididymis, in the corpus luteum, and in post-meiotic round spermatids. http://togogenome.org/gene/10090:H3c13 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Or6c210 ^@ http://purl.uniprot.org/uniprot/Q8VFH7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp12a ^@ http://purl.uniprot.org/uniprot/Q9Z1W8 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.|||Found in skin, kidney and distal colon.|||Mice are born at the expected Mendelian rate.|||The ATPase pump is composed of a catalytic alpha subunit and an auxiliary non-catalytic beta subunit. The alpha subunit pairs with the beta subunit of gastric H(+)/K(+) ATPase ATP4B or the beta subunit of Na(+)/K(+) ATPases ATP1B1 and ATP1B3; this interaction is required for the formation of a functionally active pump and its targeting at the plasma membrane.|||The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment (By similarity). Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon (PubMed:9449685). In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance (By similarity).|||Up-regulated in kidney and down-regulated in colon in response to K(+) ion free diet. http://togogenome.org/gene/10090:Or6c204 ^@ http://purl.uniprot.org/uniprot/F6VS78 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem41b ^@ http://purl.uniprot.org/uniprot/Q8K1A5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM41 family.|||Causes early embryonic lethality (PubMed:30352685). Conditional deletion in the liver leads to decreased number of circulating lipoproteins (PubMed:30352685).|||Endomembrane system|||Endoplasmic reticulum membrane|||Expressed in brain, spinal cord, kidney and first lumbar dorsal root ganglia during postnatal development. Expressed in motor neurons and proprioceptive neurons.|||Interacts with VMP1. Interacts with COPA, COPB1, VDAC1 and ERLIN2. Interacts with ATG2A. Interacts with SURF4.|||Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine. Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by ATG2 (ATG2A or ATG2B) to mediate autophagosome assembly. In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required (By similarity). Required for normal motor neuron development (By similarity).|||The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain. http://togogenome.org/gene/10090:Sntb2 ^@ http://purl.uniprot.org/uniprot/Q542S9|||http://purl.uniprot.org/uniprot/Q61235 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex. May play a role in the regulation of secretory granules via its interaction with PTPRN (By similarity).|||Belongs to the syntrophin family.|||Cell junction|||Membrane|||Monomer and homodimer (Probable). Interacts with the dystrophin protein DMD and related protein DTNA; and with the other members of the syntrophin family: SNTA1 and SNTB1. Interacts with the neuroregulin receptor ERBB4. Interacts with PTPRN when phosphorylated, protecting PTPRN from protein cleavage by CAPN1. Dephosphorylation upon insulin stimulation disrupts the interaction with PTPRN and results in the cleavage of PTPRN (By similarity). Interacts with the sodium channel proteins SCN4A and SCN5A. Interacts with SAST, MAST205, microtubules and microtubule-associated proteins. Interacts with the dystrophin related protein UTRN. Interacts with DTNB (PubMed:10893187).|||Phosphorylated. Partially dephosphorylated upon insulin stimulation (By similarity).|||The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity).|||The PH 1 domain mediates the oligomerization in a calcium dependent manner.|||The SU domain binds calmodulin in a calcium-dependent manner.|||Ubiquitous. Expressed at high levels in the testis.|||cytoskeleton|||secretory vesicle membrane http://togogenome.org/gene/10090:Tmem147 ^@ http://purl.uniprot.org/uniprot/B2RVQ1|||http://purl.uniprot.org/uniprot/Q9CQG6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM147 family.|||Cell membrane|||Component of the back of Sec61 (BOS) complex, composed of NCLN/Nicalin, NOMO (NOMO1, NOMO2 or NOMO3) and TMEM147. The BOS complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex. Interacts with CHRM3, CHRM1 and AVPR2. Interacts with LBR; promoting LBR localization to the nucleus inner membrane. Interacts with DHCR7.|||Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions. Also acts as a negative regulator of CHRM3 function, most likely by interfering with its trafficking to the cell membrane. Negatively regulates CHRM3-mediated calcium mobilization and activation of RPS6KA1/p90RSK activity. Regulates LBR localization to the nucleus inner membrane.|||Endoplasmic reticulum membrane|||Expressed in cerebral cortex, submandibular gland, hypothalamus, pancreas, liver, and ileum.|||Membrane|||Nucleus membrane http://togogenome.org/gene/10090:Nup93 ^@ http://purl.uniprot.org/uniprot/Q8BJ71 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleoporin interacting component (NIC) family.|||Nucleus envelope|||Nucleus membrane|||Part of the nuclear pore complex (NPC). Component of the p62 complex, a complex composed of NUP62 and NUP54. Forms a complex with NUP35, NUP155, NUP205 and lamin B; the interaction with NUP35 is direct. Does not interact with TPR. Interacts with SMAD4 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling.|||Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. May anchor nucleoporins, but not NUP153 and TPR, to the NPC (By similarity). During renal development, regulates podocyte migration and proliferation through SMAD4 signaling (By similarity) (PubMed:26878725).|||nuclear pore complex http://togogenome.org/gene/10090:Llgl1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0S4|||http://purl.uniprot.org/uniprot/Q80Y17 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with nonmuscle myosin II heavy chain. Interacts with PRKCI/aPKC, PARD6B/Par-6 and PARD6A (By similarity). Interacts with STX4A. Interacts with RAB10 (GDP-bound form); the interaction is direct and promotes RAB10 association with membranes and activation through competition with the Rab inhibitor GDI1. Interacts with DCAF1 (By similarity).|||Belongs to the WD repeat L(2)GL family.|||Cortical cytoskeleton protein found in a complex involved in maintaining cell polarity and epithelial integrity. Involved in the regulation of mitotic spindle orientation, proliferation, differentiation and tissue organization of neuroepithelial cells. Involved in axonogenesis through RAB10 activation thereby regulating vesicular membrane trafficking toward the axonal plasma membrane.|||Early endosome membrane|||Golgi apparatus membrane|||Mice exhibit disorganization and disruption of the apical junctional complex, resulting in hyper-proliferation of neuroblasts and brain dysplasia. Loss of Lgl1 in mice results in formation of neuroepithelial rosette-like structures, similar to the neuroblastic rosettes in human primitive neuroectodermal tumors. The newborn Lgl1(-/-) pups develop severe hydrocephalus and die neonatally. Due to the loss of mitotic spindle orientation, a large proportion of Lgl1(-/-) neural progenitor cells fails to exit the cell cycle and differentiate, and, instead, continues to proliferate and dies by apoptosis. Dividing Lgl1(-/-) cells are unable to asymmetrically localize the Notch inhibitor Numb, and the resulting failure of asymmetric cell divisions may be responsible for the hyperproliferation and the lack of differentiation.|||Phosphorylated by PRKCI on at least one of the following Ser residues: Ser 654, Ser-658, Ser-662, Ser-669 and Ser-672. Phosphorylation is important for appropriated cell polarization.|||axon|||cytoskeleton|||trans-Golgi network membrane http://togogenome.org/gene/10090:Golph3 ^@ http://purl.uniprot.org/uniprot/Q9CRA5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GOLPH3/VPS74 family.|||Cell membrane|||Endosome|||Expressed in all tissues tested including brain, heart, kidney, liver, lung, salivary gland, skeletal muscle, small intestine, spleen, stomach, skin and testis (at protein level).|||Golgi apparatus|||Golgi stack membrane|||Homodimer. Interacts with the coatomer complex. Interacts with MYO18A; the interaction is direct and may link Golgi membranes to the actin cytoskeleton. Interacts with GCNT1; may control its retention in the Golgi. Interacts with VPS35 (By similarity).|||Mitochondrion intermembrane space|||Phosphatidylinositol-4-phosphate-binding protein that links Golgi membranes to the cytoskeleton and may participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus. May also bind to the coatomer to regulate Golgi membrane trafficking. May play a role in anterograde transport from the Golgi to the plasma membrane and regulate secretion. Has also been involved in the control of the localization of Golgi enzymes through interaction with their cytoplasmic part. May play an indirect role in cell migration. Has also been involved in the modulation of mTOR signaling. May also be involved in the regulation of mitochondrial lipids biosynthesis (By similarity).|||Phosphorylated.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Inpp1 ^@ http://purl.uniprot.org/uniprot/P49442 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Belongs to the inositol monophosphatase superfamily.|||Inhibited by Li(+).|||Mg(2+)-dependent phosphatase that catalyzes the hydrolysis of the 1-position phosphate from inositol 1,4-bisphosphate and inositol 1,3,4-trisphosphate and participates in inositol phosphate metabolism.|||Monomer. http://togogenome.org/gene/10090:Ppox ^@ http://purl.uniprot.org/uniprot/P51175|||http://purl.uniprot.org/uniprot/Q3UQA3 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protoporphyrinogen/coproporphyrinogen oxidase family. Protoporphyrinogen oxidase subfamily.|||Binds 1 FAD per subunit.|||Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.|||During erythroid differentiation.|||Inhibited by acifluorfen.|||Mitochondrion inner membrane|||Monomer. Homodimer (By similarity). http://togogenome.org/gene/10090:Fthl17a ^@ http://purl.uniprot.org/uniprot/Q9DAX0 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Rho ^@ http://purl.uniprot.org/uniprot/P15409 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Contains one covalently linked retinal chromophore. Upon light absorption, the covalently bound 11-cis-retinal is converted to all-trans-retinal. After hydrolysis of the Schiff base and release of the covalently bound all-trans-retinal, active rhodopsin is regenerated by binding of a fresh molecule of 11-cis-retinal.|||Expressed in the outer segment of retinal photoreceptors at postnatal days 11 and 22.|||Homodimer (By similarity). May form a complex composed of RHO, GRK1 and RCVRN in a Ca(2+)-dependent manner; RCVRN prevents the interaction between GRK1 and RHO (By similarity). Interacts with GRK1 (By similarity). Interacts (phosphorylated form) with SAG (By similarity). Interacts with GNAT1 (By similarity). Interacts with GNAT3. SAG and G-proteins compete for a common binding site (By similarity). Interacts with PRCD; the interaction promotes PRCD stability (PubMed:27509380). Forms a complex with ASAP1 and ARF4. Forms a complex with ASAP1, RAB11A, Rabin8/RAB3IP, ARF4 and RAB11FIP3; the complex regulates Golgi-to-cilia rhodopsin/RHO transport in photoreceptors (By similarity).|||Membrane|||Mice show no response in electroretinograms at low light intensity (PubMed:9020854). They fail to form rod outer segments leading to degeneration of photoreceptor cells within 3 months of birth (PubMed:9020854, PubMed:32312889).|||Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.|||Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth (PubMed:9020854). Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change that activates signaling via G-proteins. Subsequent receptor phosphorylation mediates displacement of the bound G-protein alpha subunit by the arrestin SAG and terminates signaling (PubMed:27353443).|||Rod-shaped photoreceptor cells in the retina (at protein level).|||photoreceptor outer segment http://togogenome.org/gene/10090:Wdfy4 ^@ http://purl.uniprot.org/uniprot/E9Q2M9 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early endosome|||Endoplasmic reticulum|||Highly expressed in immune tissues, especially B lymphocytes.|||Interacts with HSP90AB1.|||Mice are unable to cross-present in vivo (PubMed:30409884). In addition, affects the development of B-cells with a block in the transition between the pro- and pre-B cell stages in bone marrow (PubMed:30257884).|||Plays a critical role in the regulation of cDC1-mediated cross-presentation of viral and tumor antigens in dendritic cells (PubMed:30409884). Mechanistically, acts near the plasma membrane and interacts with endosomal membranes to promote endosomal-to-cytosol antigen trafficking (PubMed:30409884). Also plays a role in B-cell survival through regulation of autophagy (PubMed:30257884). http://togogenome.org/gene/10090:Or2t6 ^@ http://purl.uniprot.org/uniprot/Q8VF37 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc26a5 ^@ http://purl.uniprot.org/uniprot/Q32MT6|||http://purl.uniprot.org/uniprot/Q32MT7|||http://purl.uniprot.org/uniprot/Q99NH7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Expressed in the outer hair cells (OHC) of the organ of Corti of the inner ear (PubMed:14553901, PubMed:12584604, PubMed:12782792). Also weak expression in brain and testis (PubMed:12584604). Very weakly expressed in heart, spleen, muscle and lactating mammary glands (PubMed:12584604). Expressed in cardiac myocytes (at protein level), both in the surface sarcolemma and along the t-tubule (PubMed:33951436). Weakly expressed in skeletal muscle cells (at protein level) (PubMed:33951436).|||Homodimer (By similarity). Interacts (via STAS domain) with CALM; this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).|||Homozygous knockout mice lacking Slc26a5 have no obvious developmental or behavioral abnormalities, except that, at one month, mice show small size difference compared to wild-type (PubMed:12239568). Mice show loss of electromotility, shortened outer hair cells (OHCs), and a reduction of hearing sensitivity of 40-60 dB (PubMed:12239568).|||Lateral cell membrane|||Membrane|||The STAS domain mediates dimerization, with both STAS domains latched onto each other in a domain-swapped manner. The N-terminus domain is involved in dimerization such that each N-terminus domain embraces both STAS domains (By similarity). The STAS domain harbors a unique anion-binding site important for the fine regulation of the high-frequency electromotile properties (By similarity). The transmembrane domain consists of 14 transmembrane segments organized in a 7(+)7 inverted repeat architecture that can be divided into two main helix bundles, the ''core'' domain and the ''gate'' domain (By similarity). The transmembrane regions are domain-swapped with the STAS domain containing N- and C-terminal cytoplasmic domains (By similarity). The STAS domain mediates CALM binding CALM (By similarity).|||Voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ (PubMed:12239568). Converts changes in the transmembrane electric potential into mechanical displacements resulting in the coupling of its expansion to movement of a charged voltage sensor across the lipid membrane (PubMed:12239568). The nature of the voltage sensor is not completely clear, and two models compete (By similarity). In the first model, acts as an incomplete transporter where intracellular chloride anion acts as extrinsic voltage sensor that drives conformational change in the protein which is sufficient to produce a length change in the plane of the membrane and hence in the length of the OHC (By similarity). The second model in which multiple charged amino acid residues are distributed at the intracellular and extracellular membrane interfaces that form an intrinsic voltage sensor, whose movement produces the non-linear capacitance (NLC) (By similarity). However, the effective voltage sensor may be the result of a hybrid voltage sensor, assembled from intrinsic charge (charged residues) and extrinsic charge (bound anion) (By similarity). Notably, binding of anions to the anion-binding pocket partially neutralizes the intrinsic positive charge rather than to form an electrically negative sensor, therefore remaining charge may serve as voltage sensor that, after depolarization, moves from down (expanded state) to up (contracted) conformation, which is accompanied by an eccentric contraction of the intermembrane cross-sectional area of the protein as well as a major increase in the hydrophobic thickness of the protein having as consequences the plasma membrane thickening and the cell contraction after membrane depolarization (By similarity). The anion-binding pocket transits from the inward-open (Down) state, where it is exposed toward the intracellular solvent in the absence of anion, to the occluded (Up) state upon anion binding (By similarity). Salicylate competes for the anion-binding site and inhibits the voltage-sensor movement, and therefore inhibits the charge transfer and electromotility by displacing Cl(-) from the anion-binding site and by preventing the structural transitions to the contracted state (By similarity). In addition, can act as a weak Cl(-)/HCO3(-) antiporter across the cell membrane and so regulate the intracellular pH of the outer hair cells (OHCs), while firstly found as being unable to mediate electrogenic anion transport (By similarity). Moreover, supports a role in cardiac mechanical amplification serving as an elastic element to enhance the actomyosin- based sarcomere contraction system (PubMed:33951436).|||Voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ. Converts changes in the transmembrane electric potential into mechanical displacements resulting in the coupling of its expansion to movement of a charged voltage sensor across the lipid membrane. The nature of the voltage sensor is not completely clear, and two models compete. In the first model, acts as an incomplete transporter where intracellular chloride anion acts as extrinsic voltage sensor that drives conformational change in the protein which is sufficient to produce a length change in the plane of the membrane and hence in the length of the OHC. The second model in which multiple charged amino acid residues are distributed at the intracellular and extracellular membrane interfaces that form an intrinsic voltage sensor, whose movement produces the non-linear capacitance (NLC). However, the effective voltage sensor may be the result of a hybrid voltage sensor, assembled from intrinsic charge (charged residues) and extrinsic charge (bound anion). Notably, binding of anions to the anion-binding pocket partially neutralizes the intrinsic positive charge rather than to form an electrically negative sensor, therefore remaining charge may serve as voltage sensor that, after depolarization, moves from down (expanded state) to up (contracted) conformation, which is accompanied by an eccentric contraction of the intermembrane cross-sectional area of the protein as well as a major increase in the hydrophobic thickness of the protein having as consequences the plasma membrane thickening and the cell contraction after membrane depolarization. The anion-binding pocket transits from the inward-open (Down) state, where it is exposed toward the intracellular solvent in the absence of anion, to the occluded (Up) state upon anion binding. Salicylate competes for the anion-binding site and inhibits the voltage-sensor movement, and therefore inhibits the charge transfer and electromotility by displacing Cl(-) from the anion-binding site and by preventing the structural transitions to the contracted state. In addition, can act as a weak Cl(-)/HCO3(-) antiporter across the cell membrane and so regulate the intracellular pH of the outer hair cells (OHCs), while firstly found as being unable to mediate electrogenic anion transport. Moreover, supports a role in cardiac mechanical amplification serving as an elastic element to enhance the actomyosin- based sarcomere contraction system. http://togogenome.org/gene/10090:Fmod ^@ http://purl.uniprot.org/uniprot/P50608 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Affects the rate of fibrils formation. May have a primary role in collagen fibrillogenesis.|||Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.|||Binds keratan sulfate chains.|||Binds to type I and type II collagen.|||Highest levels between 5 days and 1 month of age. Thereafter, the expression of declined to a level of approx. 35% of maximum, and remained constant throughout the rest of the observation period.|||Highest levels observed in knee epiphysis, in calvarial and diaphyseal bone, in nasal and costal cartilage, in the eye, and in bladder. In mature knee joint it is mostly present in the proliferating zone of growth plate. It is also observed in ligaments, especially at insertion sites, in the junction between meniscus and joint capsule, in the perimysium of skeletal muscle and in the periosteum.|||Sulfated on tyrosine residue(s).|||extracellular matrix http://togogenome.org/gene/10090:Glyctk ^@ http://purl.uniprot.org/uniprot/A0A0R4J1H2|||http://purl.uniprot.org/uniprot/Q8QZY2 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycerate kinase type-2 family.|||Cytoplasm|||Expressed in the hippocampus, callus, brain, cerebellum, renal cortex interstitial cells, epithelium of interlobular bile duct and skeletal muscle. http://togogenome.org/gene/10090:Vash1 ^@ http://purl.uniprot.org/uniprot/Q8C1W1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transglutaminase-like superfamily. Vasohibin family.|||Cytoplasm|||Expressed at low level in proliferating endothelial cells at the sprouting front but highly expressed in nonproliferating endothelial cells in the termination zone.|||Interacts with SVBP; interaction enhances VASH1 tyrosine carboxypeptidase activity.|||Secreted|||Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146868). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (By similarity).|||Ubiquitinated in vitro. http://togogenome.org/gene/10090:Hdac8 ^@ http://purl.uniprot.org/uniprot/Q8VH37 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone deacetylase family. HD type 1 subfamily.|||Binds 1 divalent metal cation per subunit.|||Chromosome|||Cytoplasm|||Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones.|||Interacts with CBFA2T3 (PubMed:11533236). Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation (By similarity). Associates with alpha-SMA (smooth muscle alpha-actin) (By similarity).|||Its activity is inhibited by trichostatin A (TSA) and butyrate, 2 well known histone deacetylase inhibitors. histone deacetylase inhibitor.|||Nucleus|||Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4. http://togogenome.org/gene/10090:Coq4 ^@ http://purl.uniprot.org/uniprot/B9EID1|||http://purl.uniprot.org/uniprot/Q8BGB8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COQ4 family.|||Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.|||Component of the coenzyme Q biosynthetic pathway. May play a role in organizing a multi-subunit COQ enzyme complex required for coenzyme Q biosynthesis. Required for steady-state levels of other COQ polypeptides.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Commd2 ^@ http://purl.uniprot.org/uniprot/Q8BXC6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105, NFKB2/p100. Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4B, CUL5, CUL7.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B. http://togogenome.org/gene/10090:Gask1b ^@ http://purl.uniprot.org/uniprot/Q3UPI1 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GASK family.|||Expressed in heart and midgut at 9.5 day post-conception (dpc). Expressed in floor plate, peripheral nervous system, lens epithelium, skin, midline dorsal aorta, lung, kidney and testis from 10 dpc onwards.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Or9r3 ^@ http://purl.uniprot.org/uniprot/Q7TRH2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:S100b ^@ http://purl.uniprot.org/uniprot/P50114|||http://purl.uniprot.org/uniprot/Q3UY00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the S-100 family.|||Cytoplasm|||Dimer of either two alpha chains, or two beta chains, or one alpha and one beta chain (By similarity). The S100B dimer binds two molecules of STK38 (By similarity). Interacts with CACYBP in a calcium-dependent manner (By similarity). Interacts with ATAD3A; this interaction probably occurs in the cytosol prior to ATAD3A mitochondrial targeting (By similarity). Interacts with S100A6 (By similarity). The S100B dimer interacts with two molecules of CAPZA1 (By similarity). Interacts with AGER (By similarity). Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity (By similarity). Interacts with TPPP; this interaction inhibits TPPP dimerization (By similarity). Interacts with isoform CLSTN3beta of CLSTN3; interaction promotes secretion (PubMed:31043739).|||Nucleus|||Secreted|||Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (By similarity). Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer (By similarity). Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites (By similarity). Acts as a neurotrophic factor that promotes astrocytosis and axonal proliferation (PubMed:2592414, PubMed:8202493). Involved in innervation of thermogenic adipose tissue by acting as an adipocyte-derived neurotrophic factor that promotes sympathetic innervation of adipose tissue (PubMed:31043739). Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase (By similarity). Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (By similarity). May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity (By similarity). http://togogenome.org/gene/10090:1600012H06Rik ^@ http://purl.uniprot.org/uniprot/Q9DAY5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UPF0669 family.|||May be involved in induction of apoptosis in CD4(+) T-cells, but not CD8(+) T-cells or hepatocytes.|||Secreted http://togogenome.org/gene/10090:Gpr63 ^@ http://purl.uniprot.org/uniprot/Q9EQQ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Brain specific.|||Cell membrane|||Orphan receptor. May play a role in brain function. http://togogenome.org/gene/10090:Or4f60 ^@ http://purl.uniprot.org/uniprot/Q7TQW8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dvl1 ^@ http://purl.uniprot.org/uniprot/P51141 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DSH family.|||Cell membrane|||Cytoplasmic vesicle|||High levels are seen in the brain, testis and kidney, lower levels in the ovary, breast, muscle, liver and small intestine, and very low levels are seen in the spleen and thymus. A moderate level expression is seen in the heart.|||Interacts with CXXC4 (By similarity). Interacts (via PDZ domain) with TMEM88 (By similarity). Interacts with BRD7 and INVS. Interacts (via PDZ domain) with VANGL1 and VANGL2 (via C-terminus). Interacts (via PDZ domain) with NXN. Interacts with ARRB1; the interaction is enhanced by phosphorylation of DVL1 (By similarity). Interacts with CYLD. Interacts (via PDZ domain) with RYK. Self-associates (via DIX domain) and forms higher homooligomers. Interacts (via PDZ domain) with DACT1 and FZD7, where DACT1 and FZD7 compete for the same binding site. Interacts (via DEP domain) with MUSK; the interaction is direct and mediates the formation a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering. Interacts with DCDC2. Interacts with FOXK2 (By similarity). Interacts with PKD1 (via extracellular domain) (PubMed:27214281). Interacts (via PDZ domain) with CCDC88C/DAPLE; competes with CCDC88C for binding to frizzled receptor FZD7 and dissociates from CCDC88C following initiation of non-canonical Wnt signaling when CCDC88C displaces DVL1 from ligand-activated FZD7 (By similarity).|||Is expressed throughout the embryonic central nervous system from presomite stages and in neuron-rich areas of the brain throughout postnatal development, as well as in many other tissues.|||Mice display abnormalities in social behavior and sensorimotor gating.|||Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ).|||The DEP domain mediates interaction with the cell membrane.|||The DIX domain promotes homooligomerization.|||Ubiquitinated; undergoes both 'Lys-48'-linked ubiquitination, leading to its subsequent degradation by the ubiquitin-proteasome pathway, and 'Lys-63'-linked ubiquitination. The interaction with INVS is required for ubiquitination (By similarity). Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin chains.|||cytosol http://togogenome.org/gene/10090:Zdhhc2 ^@ http://purl.uniprot.org/uniprot/P59267 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autopalmitoylated.|||Belongs to the DHHC palmitoyltransferase family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in all brain regions.|||Golgi apparatus membrane|||Monomer. Homodimer. The monomeric form has a higher catalytic activity.|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (PubMed:15603741). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable). In the nervous system, plays a role in long term synaptic potentiation by palmitoylating AKAP5 through which it regulates protein trafficking from the dendritic recycling endosomes to the plasma membrane and controls both structural and functional plasticity at excitatory synapses (PubMed:25589740). In dendrites, mediates the palmitoylation of DLG4 when synaptic activity decreases and induces synaptic clustering of DLG4 and associated AMPA-type glutamate receptors (PubMed:15603741). Also mediates the de novo and turnover palmitoylation of RGS7BP, a shuttle for Gi/o-specific GTPase-activating proteins/GAPs, promoting its localization to the plasma membrane in response to the activation of G protein-coupled receptors. Through the localization of these GTPase-activating proteins/GAPs, it also probably plays a role in G protein-coupled receptors signaling in neurons (PubMed:21343290). Also probably plays a role in cell adhesion by palmitoylating CD9 and CD151 to regulate their expression and function. Palmitoylates the endoplasmic reticulum protein CKAP4 and regulates its localization to the plasma membrane. Could also palmitoylate LCK and regulate its localization to the plasma membrane (By similarity).|||Postsynaptic density|||Postsynaptic recycling endosome membrane|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Cdc14b ^@ http://purl.uniprot.org/uniprot/Q6PFY9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class CDC14 subfamily.|||Composed of two structurally equivalent A and B domains that adopt a dual specificity protein phosphatase (DSP) fold.|||Dual-specificity phosphatase involved in DNA damage response. Essential regulator of the G2 DNA damage checkpoint: following DNA damage, translocates to the nucleus and dephosphorylates FZR1/CDH1, a key activator of the anaphase promoting complex/cyclosome (APC/C). Dephosphorylates SIRT2 around early anaphase. Dephosphorylation of FZR1/CDH1 activates the APC/C, leading to the ubiquitination of PLK1, preventing entry into mitosis. Preferentially dephosphorylates proteins modified by proline-directed kinases (By similarity).|||Interacts with FZR1/CDH1.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Rbm24 ^@ http://purl.uniprot.org/uniprot/D3Z4I3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in embryonic heart at 11.5 and 13.5 dpc (PubMed:25313962). Expressed in MyoD-expressing myoblasts at 11.5 dpc (at protein level) (PubMed:25217815). Expressed in the early cardiac mesoderm at 7 dpc (PubMed:19658189). Expressed in the cardiac crescent at 8 dpc (PubMed:19658189). Expressed in the developing heart and somites from 9.5 to 12.5 dpc (PubMed:19658189, PubMed:25313962, PubMed:25217815). Expressed in the lens, otic vesicle, heart and weakly in the mesodermal core of the first and second branchial arches at 10.5 dpc (PubMed:25217815). Expressed in all appendicular muscle masses at the forelimb and hindlimb levels and in developing head muscles at 11.5 dpc (PubMed:25217815). Expressed in appendicular muscle masses, diaphragm muscle and developing head muscles at 12.5 dpc (PubMed:25217815).|||Expressed strongly in heart and skeletal muscles (PubMed:25313962). Weakly expressed in intestine, aorta, liver, lung, kidney, uterus and bladder (PubMed:25313962).|||Interacts with EIF4E; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex.|||Mice die in utero between embryonic days 12.5 and 14.5 (PubMed:25313962, PubMed:29358667). Show multiple cardiac malformations, including defective endocardial cushion morphogenesis, ventricular septum defects, reduced trabeculation and compaction and dilated atria (PubMed:25313962, PubMed:29358667). Display loss of sarcomeres in cardiomyocytes (PubMed:25313962). Show aberrant pre-mRNA alternative splicing of key genes necessary for sarcomere formation and cardiogenesis (PubMed:25313962).|||Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation (PubMed:25313962, PubMed:26844700). Plays a major role in pre-mRNA alternative splicing regulation (PubMed:25313962, PubMed:26844700). Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation (PubMed:25313962, PubMed:26844700). Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing (PubMed:25313962). Involved in embryonic stem cell (ESC) transition to cardiac cell differentiation by promoting pre-mRNA alternative splicing events of several pluripotency and/or differentiation genes. Plays a role in the regulation of mRNA stability. Binds to 3'-untranslated region (UTR) AU-rich elements in target transcripts, such as CDKN1A and MYOG, leading to maintain their stabilities. Involved in myogenic differentiation by regulating MYOG levels. Binds to multiple regions in the mRNA 3'-UTR of TP63, hence inducing its destabilization. Promotes also the destabilization of the CHRM2 mRNA via its binding to a region in the coding sequence. Plays a role in the regulation of mRNA translation. Mediates repression of p53/TP53 mRNA translation through its binding to U-rich element in the 3'-UTR, hence preventing EIF4E from binding to p53/TP53 mRNA and translation initiation. Binds to a huge amount of mRNAs (By similarity). Required for embryonic heart development, sarcomer and M-band formation in striated muscles (PubMed:25313962, PubMed:29358667). Together with RBM20, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By similarity).|||Nucleus|||The RRM domain is necessary for mRNA stability and mRNA translation regulation.|||Up-regulated during embryonic stem cell (ESC) differentiation into cardiomyocytes (PubMed:26990106). Down-regulated by microRNA-222 (miR-222) in skeletal muscle cells, leading in inhibition of muscle-specific pre-mRNA alternative splicing events and myoblast fusion (PubMed:26844700). http://togogenome.org/gene/10090:Pfkp ^@ http://purl.uniprot.org/uniprot/Q8C605|||http://purl.uniprot.org/uniprot/Q9WUA3 ^@ Activity Regulation|||Caution|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.|||Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade "E" sub-subfamily.|||Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E' sub-subfamily.|||Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.|||Cytoplasm|||Expression is constant during tumor growth and markedly decreases when cell proliferation stops.|||GlcNAcylation decreases enzyme activity.|||Homo- and heterotetramers (By similarity). Phosphofructokinase (PFK) enzyme functions as a tetramer composed of different combinations of 3 types of subunits, called PFKM (M), PFKL (L) and PFKP (P). The composition of the PFK tetramer differs according to the tissue type it is present in. The kinetic and regulatory properties of the tetrameric enzyme are dependent on the subunit composition, hence can vary across tissues (Probable). Interacts with ATG4B; promoting phosphorylation of ATG4B.|||Homo- and heterotetramers.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be due to intron retention. http://togogenome.org/gene/10090:Acat2 ^@ http://purl.uniprot.org/uniprot/Q8CAY6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thiolase-like superfamily. Thiolase family.|||Homotetramer.|||Involved in the biosynthetic pathway of cholesterol.|||cytosol http://togogenome.org/gene/10090:Ern2 ^@ http://purl.uniprot.org/uniprot/Q32MS5|||http://purl.uniprot.org/uniprot/Q3UTN5|||http://purl.uniprot.org/uniprot/Q9Z2E3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Endoplasmic reticulum membrane|||Membrane|||Role in expression of the DDIT3 transcription factor, required for the unfolded-protein response, growth arrest and apoptosis. Has no effect on 28S ribosomal RNA cleavage, unlike the corresponding human protein.|||The kinase domain is activated by trans-autophosphorylation. Kinase activity is required for activation of the endoribonuclease domain (By similarity). http://togogenome.org/gene/10090:Or5t15 ^@ http://purl.uniprot.org/uniprot/A3KPP7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kirrel ^@ http://purl.uniprot.org/uniprot/Q80W68 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in kidney. Specifically expressed in podocytes of kidney glomeruli.|||Belongs to the immunoglobulin superfamily.|||Cell membrane|||Interacts with TJP1/ZO-1 and with NPHS2/podocin (via the C-terminus). Interacts with NPHS1/nephrin (via the Ig-like domains); this interaction is dependent on KIRREL1 glycosylation. Homodimer (via the Ig-like domains). Interacts when tyrosine-phosphorylated with GRB2 (By similarity).|||Knockout of this gene results in perinatal lethality accompanied by proteinuria, and effacement of glomerular podocytes.|||N-glycosylated.|||Phosphorylation probably regulates the interaction with NPHS2. Phosphorylated at Tyr-637 and Tyr-638 by FYN, leading to GRB2 binding (By similarity).|||Required for proper function of the glomerular filtration barrier. It is involved in the maintenance of a stable podocyte architecture with interdigitating foot processes connected by specialized cell-cell junctions, known as the slit diaphragm (PubMed:11416156). Is a signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1. http://togogenome.org/gene/10090:Ngef ^@ http://purl.uniprot.org/uniprot/Q8CHT1 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role in axon guidance regulating ephrin-induced growth cone collapse and dendritic spine morphogenesis. Upon activation by ephrin through EPHA4, the GEF activity switches toward RHOA resulting in its activation. Activated RHOA promotes cone retraction at the expense of RAC1- and CDC42-stimulated growth cone extension.|||Cytoplasm|||Highly expressed in 7 dpc and to a lower extent in 11 dpc, 15 dpc and 17 dpc embryos. Expressed at 16.5 dpc in the lateral regions of the cortex.|||Highly expressed in brain and to a lower extent in eye.|||Interacts with CDK5R1 and EPHA4; activated by EPHA4 through the CDK5 kinase.|||Membrane|||Src-dependent phosphorylation at Tyr-177 upon EPHA4 activation increases the guanine exchange factor activity toward RHOA. Phosphorylation by CDK5 upon EPHA4 activation by EFNA1 may regulate dendritic spine morphogenesis.|||The DH domain and the PH domain are both required to mediate interaction with EPHA4.|||growth cone http://togogenome.org/gene/10090:Map9 ^@ http://purl.uniprot.org/uniprot/Q3TRR0 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Binds to purified microtubules via its C-terminus.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Involved in organization of the bipolar mitotic spindle. Required for bipolar spindle assembly, mitosis progression and cytokinesis. May act by stabilizing interphase microtubules (By similarity).|||cytoskeleton|||spindle http://togogenome.org/gene/10090:St3gal6 ^@ http://purl.uniprot.org/uniprot/Q8VIB3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||Involved in the synthesis of sialyl-paragloboside, a precursor of sialyl-Lewis X determinant. Has a alpha-2,3-sialyltransferase activity toward Gal-beta1,4-GlcNAc structure on glycoproteins and glycolipids. Has a restricted substrate specificity, it utilizes Gal-beta1,4-GlcNAc on glycoproteins, and neolactotetraosylceramide and neolactohexaosylceramide, but not lactotetraosylceramide, lactosylceramide or asialo-GM1 (By similarity). http://togogenome.org/gene/10090:Tnfrsf23 ^@ http://purl.uniprot.org/uniprot/Q9ER63 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Receptor for the cytotoxic ligand TRAIL. Lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis. May protect cells against TRAIL mediated apoptosis through ligand competition. Cannot induce the NF-kappa-B pathway.|||Ubiquitous. http://togogenome.org/gene/10090:Xylt2 ^@ http://purl.uniprot.org/uniprot/Q3TZ69|||http://purl.uniprot.org/uniprot/Q3UCI0|||http://purl.uniprot.org/uniprot/Q9EPL0 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Active with either Mg(2+) or Mn(2+), but activity is highest when both are present.|||Belongs to the glycosyltransferase 14 family. XylT subfamily.|||Catalyzes the first step in the biosynthesis of chondroitin sulfate, heparan sulfate and dermatan sulfate proteoglycans, such as DCN (PubMed:17517600). Transfers D-xylose from UDP-D-xylose to specific serine residues of the core protein (By similarity).|||Contains disulfide bonds.|||Detected in brain, liver, lung, kidney, heart, spleen and testis, and at lower levels in skeletal muscle.|||Golgi apparatus membrane|||Membrane|||Monomer.|||Mutant mice are born at the expected Mendelian rate. Their livers display strongly reduced levels of heparan sulfate proteoglycan. DCN glycosylation is altered and lacks chondroitin sulfate groups. After 3 to 5 months, all mutant mice display increased liver weight. At an age of 4 to 5 months, about half of them delevop liver cysts, due to biliary epithelial cell hyperplasia. At an age of 3 and 10 months, mutant mice also display increased kidney weight due to hydronephrosis and impaired renal function, but they do not develop cysts.|||Secreted http://togogenome.org/gene/10090:Zfp770 ^@ http://purl.uniprot.org/uniprot/Q8BIQ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Six5 ^@ http://purl.uniprot.org/uniprot/P70178 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SIX/Sine oculis homeobox family.|||Nucleus|||Probably binds DNA dimer. Interacts with EYA3, and probably EYA1 and EYA2.|||Transcription factor that is thought to be involved in regulation of organogenesis. May be involved in determination and maintenance of retina formation. Binds a 5'-GGTGTCAG-3' motif present in the ARE regulatory element of ATP1A1. Binds a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 element in the myogenin promoter, and in the IGFBP5 promoter (By similarity). Thought to be regulated by association with Dach and Eya proteins, and seems to be coactivated by EYA1, EYA2 and EYA3. http://togogenome.org/gene/10090:Dynlt1a ^@ http://purl.uniprot.org/uniprot/P51807 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia (By similarity). May also be a accessory component of axonemal dynein. Plays an important role in male germ cell development and function. Candidate for involvement in male sterility.|||Belongs to the dynein light chain Tctex-type family.|||Cytoplasm|||First abundantly expressed at the pachytene stage of meiosis and persists throughout spermatogenesis.|||Golgi apparatus|||High level in testis (germ cell-specific). Expressed in sperm (at protein level). 200-fold lower in liver, brain, heart, spleen, and kidney. Levels in thymus and two embryonal carcinoma cell lines were several-fold higher than this low constitutive level.|||Homodimer (Probable). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. DYNLT1 and DYNLT3 compete for association with dynein IC (DYNC1I1 or DYNC1I2). Self-associates. Interacts with RHO (By similarity). Interacts with DYNC1I1 and DYNC1I2. Interacts with DOC2A, DOC2B and SCN10A. Interacts with PVR. Interacts with SVIL isoform 2. Interacts with GNB1; the interaction occurs in presence of guanine nucleotide-binding protein G(T) subunit gamma; the interaction diminishes the association of DYNLT1 with dynein IC (DYNC1I1 or DYNC1I2). Interacts with GNB2, GNB3 and GNB5; the interactions occur in presence of guanine nucleotide-binding protein G(T) subunit gamma. Interacts with ACVR2B and ARHGEF2 (By similarity). Interacts with DNAI4 (PubMed:30060180).|||Phosphorylated by BMPR2. The phosphorylation status is proposed to regulate the association with the cytoplasmic dynein complex and may have role in cytoplasmic dynein cargo release (By similarity).|||Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling. Involved in the regulation of mitotic spindle orientation.|||spindle http://togogenome.org/gene/10090:Cmah ^@ http://purl.uniprot.org/uniprot/Q61419 ^@ Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CMP-Neu5Ac hydroxylase family.|||Binds 1 [2Fe-2S] cluster per subunit.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in all tissues tested, except in brain.|||Inactive.|||Mice do not synthesize N-glycolylneuraminic acid (Neu5Gc).|||Sialic acids are components of carbohydrate chains of glycoconjugates and are involved in cell-cell recognition and cell-pathogen interactions. Catalyzes the conversion of CMP-N-acetylneuraminic acid (CMP-Neu5Ac) into its hydroxylated derivative CMP-N-glycolylneuraminic acid (CMP-Neu5Gc), a sialic acid abundantly expressed at the surface of many cells. http://togogenome.org/gene/10090:Taf12 ^@ http://purl.uniprot.org/uniprot/Q3UT56|||http://purl.uniprot.org/uniprot/Q8VE65 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF12 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the TATA-binding protein-free TAF complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. Component of the PCAF complex, at least composed of TADA2L/ADA2, TADA3L/ADA3, TAF5L/PAF65-beta, SUPT3H, TAF6L, TAF9, TAF10, TAF12 and TRRAP. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, STAF65-gamma/SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Interacts with ATF7 (via the transactivation domain); the interaction is prevented by sumoylation of ATF7.|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the TATA-binding protein-free TAF complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. http://togogenome.org/gene/10090:Vps26c ^@ http://purl.uniprot.org/uniprot/O35075 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. In the endosomes, drives the retriever and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling.|||Belongs to the VPS26 family.|||Component of the heterotrimeric retriever complex formed by VPS26C, VPS29 and VPS35L. Interacts with SNX17; the interaction is direct and associates SNX17 with the retriever complex. Interacts with SNX31; the interaction is direct.|||Endosome http://togogenome.org/gene/10090:Tspyl2 ^@ http://purl.uniprot.org/uniprot/Q7TQI8 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleosome assembly protein (NAP) family.|||By TGFB1 or serum in pituitary cell lines (at protein level).|||Cytoplasm|||Interacts with histones. Interacts with CASK. Part of a complex containing CASK, TBR1 and TSPYL2.|||Nucleus|||Part of the CASK/TBR1/TSPYL2 transcriptional complex which modulates gene expression in response to neuronal synaptic activity, probably by facilitating nucleosome assembly. May inhibit cell proliferation by inducing p53-dependent CDKN1A expression.|||Phosphorylation at Thr-333 impairs function on cell proliferation.|||Present at high levels in the pituitary gland and at moderate levels in adrenal gland, brain, testis and ovary. In brain, expressed both in mature neurons and progenitor cells (at protein level).|||Present widely throughout embryogenesis. Present in developing brain from 10.5 dpc to P7 (at protein level).|||Subject to X inactivation.|||Synaptic activity down-regulates TSPYL2 protein levels by inducing rapid proteasomal degradation. http://togogenome.org/gene/10090:Akr1e1 ^@ http://purl.uniprot.org/uniprot/Q9DCT1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldo/keto reductase family.|||Catalyzes the NADPH-dependent reduction of 1,5-anhydro-D-fructose (AF) to 1,5-anhydro-D-glucitol.|||Cytoplasm|||Inhibited by p-chloromercuribenzoic acid and alkyliodines.|||Monomer. http://togogenome.org/gene/10090:Slain1 ^@ http://purl.uniprot.org/uniprot/Q68FF7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLAIN motif-containing family.|||During embryonic stem cell differentiation, expression peaks at d2 and d3 (epiblast stage) (PubMed:16546155). In postimplantation embryos widely expressed throughout 6.5-7.0 dpc, followed by higher levels of expression in the headfold neurectoderm at 7.5 dpc (PubMed:16546155). At 8.5 dpc, observed in the neural tube and optic vesicles (PubMed:16546155). At 9.0-9.5 dpc, expressed at sites of imminent neural tube closure in the midbrain, hindbrain, and tailbud and in the dorsal aspects of the somites (PubMed:16546155). At 9.5 dpc, expressed within the neuroepithelium surrounding the telencephalic, mesencephalic and optic vesicles and in neural crest cells on either side of the mesencephalic vesicles, along the neural tube continuous with the tailbud, in the neural crest-derived dorsal root ganglia, in the surface ectoderm of the branchial arches as well as the primitive gut tube (PubMed:20563991). At 11.5 dpc, predominantly expressed within the forebrain, eye and neural tube, and weaker expression within the optic and oropharyngeal regions, in the epithelium of the olfactory pit, optic stalk and otic vesicle, parts of the gut tube, particularly within the lumen of the midgut loop and the stomach, in branchial arches and in the condensing mesenchyme of the developing limb buds (PubMed:20563991). At 11.5 dpc, also expressed within the neuroepithelium surrounding both the fourth and telencephalic ventricles (PubMed:20563991). At 13.5 dpc, expressed throughout the developing nervous system with most prominent expression in forebrain, midbrain and spinal cord, including the dorsal root ganglia and the olfactory bulb and within the endoderm derived midgut loop in the physiological umbilical hernia, as well as in the eye and in the main bronchi of the lung and within the developing metanephric tubules (PubMed:20563991). At 13.5 dpc, also expressed at the superficial layers of the neuroepithelium and the ependymal layers surrounding the fourth and lateral ventricles and in neurons of the dorsal root ganglia and in dorsal roots between the cartilage primordia as well as in cranial sensory ganglia (PubMed:20563991). Also expressed along the apical epidermal ridge and in the forelimb and hind limb (PubMed:20563991).|||Expressed in embryonic stem cells (PubMed:16546155). Expressed in adult bone marrow, brain, kidney, lung, testis and thymus (PubMed:16546155, PubMed:20563991). Expressed in colon (PubMed:20563991). Isoform 1 is highly expressed in brain (PubMed:20563991). Isoform 2 is more widely expressed in bone marrow, brain, colon, kidney, lung and thymus (PubMed:20563991).|||Interacts with MAPRE1, MAPRE2, MAPRE3 and CKAP5 (PubMed:21646404). Interacts with ZDHHC17 (via ANK repeats) (By similarity).|||Microtubule plus-end tracking protein that might be involved in the regulation of cytoplasmic microtubule dynamics, microtubule organization and microtubule elongation.|||cytoskeleton http://togogenome.org/gene/10090:Rhox2f ^@ http://purl.uniprot.org/uniprot/A2ANE0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Senp5 ^@ http://purl.uniprot.org/uniprot/Q6NXL6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C48 family.|||Interacts with CCAR2.|||Protease that catalyzes two essential functions in the SUMO pathway: processing of full-length SUMO3 to its mature form and deconjugation of SUMO2 and SUMO3 from targeted proteins. Has weak proteolytic activity against full-length SUMO1 or SUMO1 conjugates. Required for cell division.|||nucleolus http://togogenome.org/gene/10090:Atp13a2 ^@ http://purl.uniprot.org/uniprot/E9Q2A4|||http://purl.uniprot.org/uniprot/Q9CTG6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATPase which acts as a lysosomal polyamine exporter with high affinity for spermine (By similarity). Also stimulates cellular uptake of polyamines and protects against polyamine toxicity (By similarity). Plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (By similarity). Contributes to cellular zinc homeostasis (By similarity). Confers cellular protection against Mn(2+) and Zn(2+) toxicity and mitochondrial stress (By similarity). Required for proper lysosomal and mitochondrial maintenance (By similarity). Regulates the autophagy-lysosome pathway through the control of SYT11 expression at both transcriptional and post-translational levels (PubMed:27278822). Facilitates recruitment of deacetylase HDAC6 to lysosomes to deacetylate CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Promotes secretion of exosomes as well as secretion of SCNA via exosomes (By similarity). Plays a role in lipid homeostasis (By similarity).|||Accumulates in an inactive autophosphorylated state. The presence of spermine results in a dose-dependent reduction in autophosphorylation.|||Autophosphorylated. Accumulates in an inactive autophosphorylated state and autophosphorylation is stimulated by phosphatidic acid and phosphatidylinositol 3,5-bisphosphate but not by Mn(2+) or Zn(2+). The presence of spermine results in a dose-dependent reduction in autophosphorylation.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.|||Interacts with MYCBP2; the interaction inhibits the ubiquitination of TSC2 by MYCBP2 (By similarity). Interacts with HDAC6; the interaction results in recruitment of HDAC6 to lysosomes to promote CTTN deacetylation (By similarity).|||Late endosome membrane|||Lysosome membrane|||Membrane|||No visible phenotype at 4 months (PubMed:30538141). At 10 months, gradual loss of body weight, increased liver size and reduced adipose tissue mass (PubMed:30538141). These phenotypes further progress to 18 months with significantly smaller body size, hepatomegaly, increased intracellular vacuolation in liver tissues, markedly reduced adipose tissue with small adipocytes, accumulation of autophagy receptor Sqstm1/p62 and autophagy-related protein LC3 in liver, and accumulation of ubiquitinated insoluble proteins (PubMed:30538141).|||The N-terminal region is required for targeting to late endosomes/lysosomes. It does not traverse the membrane but contains a membrane-embedded intramembrane domain and interacts with the lipids phosphatidic acid (PA) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PA and PI(3,5)P2 are required for the protective effect against mitochondrial stress.|||autophagosome membrane|||multivesicular body membrane http://togogenome.org/gene/10090:Sar1b ^@ http://purl.uniprot.org/uniprot/Q0VGU0|||http://purl.uniprot.org/uniprot/Q9CQC9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. SAR1 family.|||Embryonic lethality during late-gestation (PubMed:33964306). Mice display gastrointestinal abnormalities associated with chylomicron retention disease: they show lower plasma levels of triglycerides, total cholesterol, and HDL-cholesterol, along with reduced chylomicron secretion following gastric lipid gavage (PubMed:33964306). Conditional deletion in the liver depletes plasma lipids (PubMed:33186557).|||Endoplasmic reticulum membrane|||GTP-binding protein involved in transport from the endoplasmic reticulum to the Golgi apparatus. Activated by the guanine nucleotide exchange factor PREB. Involved in the selection of the protein cargo and the assembly of the COPII coat complex (By similarity). Synergizes with the cargo receptor SURF4 to mediate the export of lipoproteins from the endoplasmic reticulum, thereby regulating lipoprotein delivery and the maintenance of lipid homeostasis (By similarity).|||Golgi stack membrane|||Homodimer (By similarity). Binds PREB (PubMed:11422940). Part of the COPII coat complex. Binds to the cytoplasmic tails of target proteins in the endoplasmic reticulum (By similarity). Interacts with SURF4 (By similarity). http://togogenome.org/gene/10090:Nap1l2 ^@ http://purl.uniprot.org/uniprot/P51860 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acidic protein which may be involved in interactions with other proteins or DNA.|||Belongs to the nucleosome assembly protein (NAP) family.|||Brain, specifically expressed in neurons.|||First expressed around the day 7 embryo.|||Nucleus http://togogenome.org/gene/10090:Pou6f2 ^@ http://purl.uniprot.org/uniprot/Q8BJI4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 18 dpc, expressed in kidney, adrenal gland, heart, stomach, muscle and eye, but not in lung and skin.|||Belongs to the POU transcription factor family. Class-6 subfamily.|||Expressed in kidney, heart, muscle, spleen and ovary, but not in lung.|||Nucleus|||Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells. Recognizes and binds to the DNA sequence 5'-ATGCAAAT-3' (By similarity). http://togogenome.org/gene/10090:Fbxo42 ^@ http://purl.uniprot.org/uniprot/Q6PDJ6 ^@ Function|||Subunit ^@ Component of some SCF complex, composed of CUL1, SKP1, RBX1 and FBXO42. Interacts (via the kelch domain) with p53/TP53; interaction is direct (By similarity).|||Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Specifically recognizes p53/TP53, promoting its ubiquitination and degradation (By similarity). http://togogenome.org/gene/10090:Acp5 ^@ http://purl.uniprot.org/uniprot/Q05117 ^@ Cofactor|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 2 iron ions per subunit.|||Characteristic constituent of osteoclasts.|||Exists either as monomer or, after proteolytic processing, as a dimer of two chains linked by disulfide bond(s).|||Induced by TNFSF11/RANKL-stimulation of bone marrow-derived macrophages.|||Lysosome|||May play a role in the process of bone resorption. The osteoclastic trap acts on nucleotide tri- and diphosphates with higher affinity, compared with other substrates. http://togogenome.org/gene/10090:Chmp5 ^@ http://purl.uniprot.org/uniprot/Q9D7S9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||Endosome membrane|||ISGylated. Isgylation inhibits its interaction with VTA1 (By similarity).|||Midbody|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4 (By similarity).|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with VTA1. Interacts with CHMP2A. Interacts with VTA1; the interaction involves soluble CHMP5 (By similarity). Interacts with NOD2 (By similarity). Interacts with BROX (By similarity).|||cytosol http://togogenome.org/gene/10090:Magi3 ^@ http://purl.uniprot.org/uniprot/G5E8T6|||http://purl.uniprot.org/uniprot/Q9EQJ9 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes. Cooperates with PTEN to modulate the kinase activity of AKT1. Its interaction with PTPRB and tyrosine phosphorylated proteins suggests that it may link receptor tyrosine phosphatase with its substrates at the plasma membrane. In polarized epithelial cells, involved in efficient trafficking of TGFA to the cell surface. Regulates the ability of LPAR2 to activate ERK and RhoA pathways. Regulates the JNK signaling cascade via its interaction with FZD4 and VANGL2.|||Belongs to the MAGUK family.|||Cell membrane|||Interacts with ADRB1, ADGRB1, LPAR2/EDG4, GRIN2B, PTEN, and PTPRB. Interacts with unidentified tyrosine phosphorylated proteins (By similarity). Interacts with FZD4, FZD7, TGFA and VANGL2. Interacts with DLL1 (PubMed:15509766). Interacts with PRRG4 (via cytoplasmic domain) (By similarity).|||Membrane|||Nucleus|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||Widely expressed. Colocalizes with TGFA in neurons in the cortex and dentate gyrus, as well as in ependymal cells and some astrocytes (at protein level). Present in lens epithelium.|||tight junction http://togogenome.org/gene/10090:H1f10 ^@ http://purl.uniprot.org/uniprot/Q80ZM5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the histone H1/H5 family.|||Nucleus http://togogenome.org/gene/10090:Cytip ^@ http://purl.uniprot.org/uniprot/Q91VY6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ By its binding to cytohesin-1 (CYTH1), it modifies activation of ARFs by CYTH1 and its precise function may be to sequester CYTH1 in the cytoplasm.|||Cytoplasm|||Early endosome|||Interacts with CYTH1 and SNX27. http://togogenome.org/gene/10090:Oma1 ^@ http://purl.uniprot.org/uniprot/Q9D8H7 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1) (PubMed:24550258, PubMed:24719224). Autocatalytic processing at the C-terminus takes place at residues 443-452 (PubMed:24719224). The S-OMA1 form is unstable (PubMed:24719224). Degradaded by YMEL1 in response to membrane depolarization (By similarity). Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner (PubMed:31819158).|||Belongs to the peptidase M48 family.|||Binds 1 zinc ion per subunit.|||Homooligomer.|||May form a redox-dependent disulfide bond (By similarity). Exists in a semi-oxidized state and is activated by prolonged hypoxia (By similarity).|||Metalloprotease that is part of the quality control system in the inner membrane of mitochondria (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24719224, PubMed:24616225, PubMed:26785494). Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24616225, PubMed:26785494). Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion (PubMed:20038678, PubMed:22433842, PubMed:24550258, PubMed:24616225, PubMed:26785494, PubMed:26783299). Also acts as a regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage of OPA1, leading to the remodeling of mitochondrial cristae and allowing the release of cytochrome c from mitochondrial cristae (By similarity). In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome (By similarity). May also cleave UQCC3 in response to mitochondrial depolarization (By similarity). Also acts as an activator of the integrated stress response (ISR): in response to mitochondrial stress, mediates cleavage of DELE1 to generate the processed form of DELE1 (S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR (By similarity). Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions (PubMed:22433842). Binds cardiolipin, possibly regulating its protein turnover (PubMed:31819158). Required for the stability of the respiratory supercomplexes (PubMed:26365306).|||Mice develop normally with males and females being fertile (PubMed:22433842). They however display transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters (PubMed:22433842). Moreover, mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis (PubMed:22433842). Mice are protected against heart failure by averting cardiomyocyte death in different murine heart failure models (PubMed:29593106). Mice with a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 have normal cardiac function and do not display myocardial fibrosis, contrary to mice with a single, cardiomyocyte-specific disruption of Yme1l (PubMed:26785494). Likewise, cardiomyocyte mitochondria have normal morphology (PubMed:26785494). Mice with a skeletal muscle Yme1l gene disruption plus a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 display normal glucose tolerance (PubMed:26785494).|||Mitochondrion inner membrane|||Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization.|||The stress-sensor region regulates proteolysis and activation. http://togogenome.org/gene/10090:Usp40 ^@ http://purl.uniprot.org/uniprot/Q8BWR4 ^@ Similarity ^@ Belongs to the peptidase C19 family. http://togogenome.org/gene/10090:Or51f1d ^@ http://purl.uniprot.org/uniprot/Q8VG25 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5h23 ^@ http://purl.uniprot.org/uniprot/L7N1Z8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ms4a8a ^@ http://purl.uniprot.org/uniprot/Q99N10 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed strongly in intestine and colon and minimally in lung and ovary.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane|||Not found in strain C57BL/6J but has been identified in strains DBA/2J and FVB/N.|||Probable cloning artifact. http://togogenome.org/gene/10090:Sema6c ^@ http://purl.uniprot.org/uniprot/E9Q613|||http://purl.uniprot.org/uniprot/Q9WTM3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the semaphorin family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be a stop signal for the dorsal root ganglion neurons in their target areas, and possibly also for other neurons. May also be involved in the maintenance and remodeling of neuronal connections (By similarity). http://togogenome.org/gene/10090:Fam83c ^@ http://purl.uniprot.org/uniprot/A2ARK0 ^@ Caution|||Function|||Similarity|||Subunit ^@ Belongs to the FAM83 family.|||It is uncertain whether Met-1 or Met-47 is the initiator.|||May interact with RAF1.|||May play a role in MAPK signaling. http://togogenome.org/gene/10090:Rnf103 ^@ http://purl.uniprot.org/uniprot/Q9R1W3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an E2-dependent E3 ubiquitin-protein ligase, probably involved in the ER-associated protein degradation pathway.|||Endoplasmic reticulum membrane|||Highly expressed in the normal cerebellum but not in the cerebral cortex.|||Interacts with DERL1 and VCP. http://togogenome.org/gene/10090:Dmp1 ^@ http://purl.uniprot.org/uniprot/O55188 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (PubMed:29148101).|||Expressed in tooth particularly in odontoblast, ameloblast and cementoblast. Also expressed in bone particularly in osteoblast.|||Interacts with importin alpha.|||May have a dual function during osteoblast differentiation. In the nucleus of undifferentiated osteoblasts, unphosphorylated form acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the osteoblast to osteocyte transition phase it is phosphorylated and exported into the extracellular matrix, where it regulates nucleation of hydroxyapatite (By similarity).|||Mice display rickets and osteomalacia with isolated renal phosphate wasting associated with elevated FGF23 levels and normocalciuria.|||Nucleus|||Phosphorylated in the cytosol and extracellular matrix and unphosphorylated in the nucleus. Phosphorylation is necessary for nucleocytoplasmic transport and may be catalyzed by a nuclear isoform of CK2 and can be augmented by calcium. Phosphorylated (in vitro) by FAM20C in the extracellular medium at sites within the S-x-E/pS motif (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Myom3 ^@ http://purl.uniprot.org/uniprot/A2ABU4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer.|||M line|||Mainly expressed in slow muscle, extraocular muscle and embryonic/neonatal skeletal muscle (at protein level). Expression in skeletal muscle is fiber type specific, with the highest levels in type IIA fibers (intermediate speed) and lower levels in type I fibers.|||May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle. http://togogenome.org/gene/10090:Ikzf2 ^@ http://purl.uniprot.org/uniprot/P81183 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with Ikaros at centromeric heterochromatin.|||Belongs to the Ikaros C2H2-type zinc-finger protein family.|||Interacts with IKZF4 and IKZF5.|||Nucleus|||Restricted to the T-cell lineage. Abundant in thymus, low expression in bone marrow and brain and no detectable expression in spleen, liver, kidney or muscle. http://togogenome.org/gene/10090:Adgrg3 ^@ http://purl.uniprot.org/uniprot/Q8R0T6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Membrane|||No visible phenotype. Mutant mice show altered follicular-versus-marginal zone B-lymphocyte fate decision in the spleen and decreased numbers of B220+ lymphocytes in the bone marrow.|||Orphan receptor that regulates migration of lymphatic endothelial cells via the small GTPases RhoA and CDC42 (By similarity). Regulates B-cell development (PubMed:24113187). Seems to signal through G-alpha(q)-proteins (By similarity).|||Specifically expressed in intestinal lymphatic endothelium. http://togogenome.org/gene/10090:Or8g2 ^@ http://purl.uniprot.org/uniprot/Q8VFN5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Crp ^@ http://purl.uniprot.org/uniprot/P14847 ^@ Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pentraxin family.|||Binds 2 calcium ions per subunit.|||Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells.|||Found in plasma.|||Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits. Interacts with FCN1; may regulate monocyte activation by FCN1 (By similarity).|||Secreted|||The concentration of CRP in plasma increases greatly during acute phase response to tissue injury, infection or other inflammatory stimuli. http://togogenome.org/gene/10090:Mocs3 ^@ http://purl.uniprot.org/uniprot/A2BDX3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Cytoplasm|||In the N-terminal section; belongs to the HesA/MoeB/ThiF family. UBA4 subfamily.|||Interacts with NFS1.|||Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards URM1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; NFS1 acting as a sulfur donor for thiocarboxylation reactions. http://togogenome.org/gene/10090:Trh ^@ http://purl.uniprot.org/uniprot/Q62361 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRH family.|||Functions as a regulator of the biosynthesis of TSH in the anterior pituitary gland and as a neurotransmitter/ neuromodulator in the central and peripheral nervous systems.|||Secreted|||Specifically expressed in hypothalamus and testis. http://togogenome.org/gene/10090:Riox1 ^@ http://purl.uniprot.org/uniprot/Q9JJF3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ROX family. NO66 subfamily.|||Binds 1 Fe(2+) ion per subunit.|||Interacts with SP7/OSX; the interaction is direct (PubMed:19927124). Interacts with PHF19; leading to its recruitment to H3K36me3 sites (By similarity). Interacts with MYC (By similarity).|||Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase (PubMed:19927124). Specifically demethylates 'Lys-4' (H3K4me) and 'Lys-36' (H3K36me) of histone H3, thereby playing a central role in histone code (PubMed:19927124). Preferentially demethylates trimethylated H3 'Lys-4' (H3K4me3) and monomethylated H3 'Lys-4' (H3K4me1) residues, while it has weaker activity for dimethylated H3 'Lys-36' (H3K36me2) (PubMed:19927124). Acts as a regulator of osteoblast differentiation via its interaction with SP7/OSX by demethylating H3K4me and H3K36me, thereby inhibiting SP7/OSX-mediated promoter activation (PubMed:19927124). Also catalyzes demethylation of non-histone proteins, such as CGAS: demethylation of monomethylated CGAS promotes interaction between CGAS and PARP1, followed by PARP1 inactivation (PubMed:35210392). Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His-216', thereby playing a role in ribosome biogenesis (By similarity). Participates in MYC-induced transcriptional activation (By similarity).|||Present in developing bones (at protein level) (PubMed:19927124). Widely but not ubiquitously expressed (PubMed:19927124).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Slc38a8 ^@ http://purl.uniprot.org/uniprot/Q5HZH7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Electrogenic sodium-dependent amino acid transporter with a preference for L-glutamine, L-alanine, L-histidine, L-aspartate and L-arginine. May facilitate glutamine uptake in both excitatory and inhibitory neurons. The transport mechanism and stoichiometry remain to be elucidated.|||Expressed in neurons located in the gray matter. Highly expressed in thalamus, hypothalamus, amygdala and pons. Expressed in the CA3 area of hippocampus and in the Purkinje layer of the cerebellum (at protein level) (PubMed:25451601). Expressed in the eye.|||Membrane|||axon|||cell cortex http://togogenome.org/gene/10090:Arf4 ^@ http://purl.uniprot.org/uniprot/P61750|||http://purl.uniprot.org/uniprot/Q14BR4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport.|||GTP-binding protein involved in protein trafficking; modulates vesicle budding and uncoating within the Golgi apparatus.|||GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus. Part of the ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which direct preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (By similarity).|||Golgi apparatus|||Membrane http://togogenome.org/gene/10090:Ptpra ^@ http://purl.uniprot.org/uniprot/P18052|||http://purl.uniprot.org/uniprot/Q91V35 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.|||Cell membrane|||Integrin binding to extracellular matrix induces phosphorylation at Tyr-825 which induces PTPRA localization and recruitment of BCAR3, BCAR1 and CRK to focal adhesions.|||Membrane|||Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain), and SRC (PubMed:22801373). Within the complex, interacts (when phosphorylated on Tyr-825) with BCAR3 (via SH2 domain) (PubMed:22801373). Interacts with GRB2 (PubMed:22801373).|||Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation (PubMed:22801373). Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42 (PubMed:22801373).|||Widely expressed. Highest expression in brain and kidney.|||focal adhesion http://togogenome.org/gene/10090:Adam39 ^@ http://purl.uniprot.org/uniprot/Q7M762 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Vmn1r174 ^@ http://purl.uniprot.org/uniprot/E9PYW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zranb3 ^@ http://purl.uniprot.org/uniprot/Q6NZP1 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Chromosome|||DNA annealing helicase and endonuclease required to maintain genome stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events. Recruited to the sites of stalled DNA replication by polyubiquitinated PCNA and acts as a structure-specific endonuclease that cleaves the replication fork D-loop intermediate, generating an accessible 3'-OH group in the template of the leading strand, which is amenable to extension by DNA polymerase. In addition to endonuclease activity, also catalyzes the fork regression via annealing helicase activity in order to prevent disintegration of the replication fork and the formation of double-strand breaks.|||In contrast to classical helicases that unwing DNA, annealing helicases rewind it.|||Interacts (via PIP-box and RanBP2-type zinc finger) with PCNA (when PCNA is polyubiquitinated via 'Lys-63'-linked polyubiquitin).|||Nucleus|||The PIP-box mediates the interaction with PCNA, while the RanBP2-type zinc finger mediates binding to 'Lys-63'-linked polyubiquitin. http://togogenome.org/gene/10090:Foxg1 ^@ http://purl.uniprot.org/uniprot/Q3V1Q8|||http://purl.uniprot.org/uniprot/Q60987 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ CNS, and nasal half of the retina.|||Interacts with KDM5B (By similarity). Interacts with GRG6/TLE6 (PubMed:16314515). Interacts with TLE1; the interaction is inhibited by interaction with TLE6/GRG6 (PubMed:16314515).|||Nucleus|||Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon. http://togogenome.org/gene/10090:Gpr137b ^@ http://purl.uniprot.org/uniprot/A0A0R4J022|||http://purl.uniprot.org/uniprot/A0A1Y7VLJ5|||http://purl.uniprot.org/uniprot/Q8BNQ3 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts also as a negative regulator of osteoclast activity (PubMed:31173907). Involved in interleukin-4-induced M2 macrophage polarization (PubMed:30595385).|||Belongs to the GPR137 family.|||Interaction with RRAGA; increases RRAGA recruitment to lysosomes. Interacts with MTOR; this interaction is amino acid sensitive.|||Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Interacts with Rag GTPases and increases the lysosomial localization and activity of Rag GTPases and thereby regulates mTORC1 translocation and activity in lysosome. Involved in the regulation of lysosomal morphology and autophagy (By similarity). Acts also as a negative regulator of osteoclast activity (PubMed:31173907). Involved in interleukin-4-induced M2 macrophage polarization (PubMed:30595385).|||Lysosome membrane|||Membrane|||Up-regulated during osteoclastogenesis (in vitro).|||Widely expressed with high expression in bone marrow and kidney (PubMed:30595385). Highly expressed in osteoclasts (at protein level) (PubMed:31173907). http://togogenome.org/gene/10090:Pla2g7 ^@ http://purl.uniprot.org/uniprot/Q60963 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response (PubMed:10066756, PubMed:18434304). At the lipid-aqueous interface, hydrolyzes the ester bond of fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10066756, PubMed:18434304). Specifically targets phospholipids with a short-chain fatty acyl group at sn-2 position. Can hydrolyze phospholipids with long fatty acyl chains, only if they carry oxidized functional groups (By similarity). Hydrolyzes and inactivates platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent pro-inflammatory signaling lipid that acts through PTAFR on various innate immune cells (PubMed:10066756, PubMed:18434304). Hydrolyzes oxidatively truncated phospholipids carrying an aldehyde group at omega position, preventing their accumulation in lipoprotein particles and uncontrolled pro-inflammatory effects (By similarity). As part of high-density lipoprotein (HDL) particles, can hydrolyze phospholipids having long-chain fatty acyl hydroperoxides at sn-2 position and protect against potential accumulation of these oxylipins in the vascular wall (By similarity). Catalyzes the release from membrane phospholipids of F2-isoprostanes, lipid biomarkers of cellular oxidative damage (By similarity).|||Mutant mice show increased susceptibility to neonatal necrotizing enterocolitis in response to formula feeding, bacterial colonization, and asphyxia/ cold stress.|||N-glycosylated.|||Plasma.|||extracellular space http://togogenome.org/gene/10090:Akt2 ^@ http://purl.uniprot.org/uniprot/Q3TY95|||http://purl.uniprot.org/uniprot/Q60823|||http://purl.uniprot.org/uniprot/Q8CE74 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinases, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Involved in the inhibition of ciliogenesis associated with RAB8-dependent cilia growth (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.|||Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PIK3CA) results in its targeting to the plasma membrane.|||Cell membrane|||Cytoplasm|||Early endosome|||In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.|||Interacts (via PH domain) with MTCP1, TCL1A and TCL1B. Interacts with CLK2, PBH2 and TRAF6. Interacts (when phosphorylated) with CLIP3, the interaction promotes cell membrane localization (By similarity). Interacts with BTBD10 (PubMed:18160256). Interacts with KCTD20 (PubMed:24156551). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529, PubMed:20189988).|||Nucleus|||O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1.|||One of the few specific substrates of AKT2 identified so far is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Phosphorylates CLK2 on 'Thr-343'.|||Phosphorylation on Thr-309 and Ser-474 is required for full activity.|||Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation.|||Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT2 ubiquitination. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome (By similarity). http://togogenome.org/gene/10090:Crhbp ^@ http://purl.uniprot.org/uniprot/Q3UY07|||http://purl.uniprot.org/uniprot/Q60571 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CRF-binding protein family.|||Binds CRF and inactivates it. May prevent inappropriate pituitary-adrenal stimulation in pregnancy.|||Secreted http://togogenome.org/gene/10090:Scrg1 ^@ http://purl.uniprot.org/uniprot/O88745 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SCRG1 family.|||Expressed at higher levels in the brains of scrapie-infected animals.|||Secreted http://togogenome.org/gene/10090:Ola1 ^@ http://purl.uniprot.org/uniprot/Q9CZ30 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. YchF/OLA1 subfamily.|||Cytoplasm|||Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP.|||Monomer.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Nrcam ^@ http://purl.uniprot.org/uniprot/Q810U4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.|||Cell adhesion protein that is required for normal responses to cell-cell contacts in brain and in the peripheral nervous system. Plays a role in neurite outgrowth in response to contactin binding (PubMed:11564762). Plays a role in mediating cell-cell contacts between Schwann cells and axons (PubMed:20188654). Plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters (PubMed:14602817, PubMed:20188654). Required, together with GLDN, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier (PubMed:24719088).|||Cell membrane|||Constituent of a NFASC/NRCAM/ankyrin-G complex (Probable). Detected in a complex with CNTN1 and PTPRB (PubMed:11564762). Interacts with GLDN/gliomedin and MYOC (PubMed:16039564, PubMed:23897819).|||Detected in sciatic nerve (PubMed:14602817, PubMed:20188654, PubMed:24719088). Detected in brain, especially in the cerebellum Purkinje cell layer, inner granule cell layer and molecular layer (at protein level) (PubMed:11564762). Detected in neurons and Schwann cells (PubMed:20188654).|||Mice are born at the expected Mendelian rate, are viable and fertile. They present no obvious phenotype excepting subtle size differences of cerebellar lobes IV and V. Contrary to wild-type, cerebellar cells do not form neurites when plated on a surface coated with contactin (in vitro) (PubMed:11564762). Neonates present delayed formation of sodium channel clusters at developing nodes of Ranvier, but are indistiguishable from wild-type at 10 days after birth (PubMed:14602817, PubMed:20188654). Mice lacking both Gldn and Nrcam are born at the expected Mendelian rate, but are smaller than control littermates and display important neurological impairments, in spite of seemingly normal nerve myelination. Motor abnormalities vary between individuals, ranging from ataxia, uncoordinated movements and premature death to weakness of the hind limbs, hypomotility, strongly impaired ability to hang from a horizontal bar with their forelimbs and a tendency to stumble. The motor defects correlate with decreased velocity of nerve conduction and slower propagation of action potentials. Most mice die within 60 days after birth, and none are fertile. Mutant mice display delayed formation of mature nodes of Ranvier; 15 days after birth about 20% of the nodes lack detectable sodium channel clusters. Sodium channel clustering and nerve conduction appear normal 60 and 75 days after birth, but subsequently a gradual disintegration of the nodal protein complexes is seen. About 70% of the mutant nodes present high-density sodium channel clustering at 120 days after birth, as opposed to nearly 100% for wild-type. Contrary to wild-type, in adult nodes of Ranvier the sodium channels are often clustered near the paranode border with an empty gap in the middle. At nodes of Ranvier, Schwann cell microvilli are sparse or absent and show defects in their orientation, resulting in various structural abnormalities at the node and the paranode border (PubMed:24719088).|||Secreted|||axon http://togogenome.org/gene/10090:Pfkfb3 ^@ http://purl.uniprot.org/uniprot/A0A0A6YY64|||http://purl.uniprot.org/uniprot/A2AUP1|||http://purl.uniprot.org/uniprot/A2AUP5|||http://purl.uniprot.org/uniprot/A7UAK4|||http://purl.uniprot.org/uniprot/A7UAK5|||http://purl.uniprot.org/uniprot/A7UAK8|||http://purl.uniprot.org/uniprot/Q3U3S6|||http://purl.uniprot.org/uniprot/Q7TS91|||http://purl.uniprot.org/uniprot/Q8BVM1 ^@ Similarity ^@ In the C-terminal section; belongs to the phosphoglycerate mutase family. http://togogenome.org/gene/10090:Ushbp1 ^@ http://purl.uniprot.org/uniprot/Q8R370 ^@ Similarity|||Subunit ^@ Belongs to the MCC family.|||Interacts via its C-terminus with the first PDZ domain of USH1C. http://togogenome.org/gene/10090:Ppp3r2 ^@ http://purl.uniprot.org/uniprot/Q497S1|||http://purl.uniprot.org/uniprot/Q63811 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcineurin regulatory subunit family.|||Expressed in osteoblasts and bone marrow (at protein level) (PubMed:16286645). Expressed in the testis (PubMed:1325794, PubMed:34446558). Expressed in the sperm midpiece in a SPATA33-dependent manner (at protein level) (PubMed:34446558).|||Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2) (By similarity). Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558).|||Mitochondrion|||Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.|||This protein has four functional calcium-binding sites. http://togogenome.org/gene/10090:Aldoart2 ^@ http://purl.uniprot.org/uniprot/A6ZI47 ^@ Similarity ^@ Belongs to the class I fructose-bisphosphate aldolase family. http://togogenome.org/gene/10090:Il22ra1 ^@ http://purl.uniprot.org/uniprot/Q80XZ4 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type II cytokine receptor family.|||By LPS stimulation in the liver.|||Cell membrane|||Component of the receptor for IL20, IL22 and IL24. Component of IL22 receptor formed by IL22RA1 and IL10RB enabling IL22 signaling via JAK/STAT pathways. IL22 also induces activation of MAPK1/MAPK3 and Akt kinases pathways. Component of one of the receptor for IL20 and IL24 formed by IL22RA1 and IL20RB also signaling through STATs activation. Mediates IL24 antiangiogenic activity as well as IL24 inhibitory effect on endothelial cell tube formation and differentiation.|||Expressed in kidney, liver and lung.|||Heterodimer with IL10RB and with IL20RB.|||Phosphorylated by GSK3-BETA and MAPK; phosphorylation by GSK3-BETA stabilizes IL22RA1 by preventing its proteasomal degradation. http://togogenome.org/gene/10090:Or6c76b ^@ http://purl.uniprot.org/uniprot/Q7TRH5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Klrk1 ^@ http://purl.uniprot.org/uniprot/O54709|||http://purl.uniprot.org/uniprot/Q3TCW7|||http://purl.uniprot.org/uniprot/Q4FJM0 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in NK cells from the thymus at 15 dpc (at protein level).|||Expressed in natural killer (NK) cells, activated CD8(+) alpha-beta and gamma-delta T-cells and natural killer T (NKT) cells (at protein level). May be expressed on dendritic cell (DC). Isoform 1 is strongly expressed in natural killer (NK) cells. Isoform 2 is weakly expressed in natural killer (NK) cells. Isoform 1 and isoform 2 are expressed in stimulated, but not in unstimulated, CD8(+) T-cells and macrophages.|||Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including RAET1A, RAET1B, RAET1C, RAET1D, RAET1E, H60 and MULT1.|||Homodimer; disulfide-linked. Heterohexamer composed of two subunits of KLRK1 and four subunits of HCST/DAP10 (By similarity). Isoform 1 (via transmembrane domain) interacts with HCST/DAP10; the interaction is required for KLRK1 cell surface expression on activated CD8(+) T-cells, but is dispensable on activated TYROBP-expressing NK cells. Isoform 2 (via transmembrane domain) interacts with HCST/DAP10 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Isoform 2 (via transmembrane domain) interacts with TYROBP (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induce NK cell-mediated cytotoxicity and cytokine secretion. Isoform 1 does not interact with TYROBP. Interacts with CEACAM1; recruits PTPN6 that dephosphorylates VAV1 (By similarity).|||Involved in autoreactive CD8(+) T-cell-mediated development of autoimmune diabetes.|||Is not capable of signal transduction by itself; isoform 1 operates either through the signaling adapter protein HCST and isoform 2 through both HCST and TYROBP signaling adapter proteins (PubMed:12426564). Some families of ligands for mouse and human KLRK1 receptors have been characterized being very similar in structure and highly likely to be orthologs. In humans, an additional distinct subfamily of ligands (MICA and MICB) differs structurally, having an extra MHC alpha 3-like domain (PubMed:23298206).|||Mice display no visible phenotype. According to PubMed:18394936, show normal development of NK cells, B and T cells but display enhanced formation of aggressive tumors. According to PubMed:19631564, exhibit developmental perturbation in size of NK cell subpopulations, increased proliferation, faster maturation and increased sensitivity to apoptosis of immature NK cells, and lower cytolytic response to KLRK1-sensitive tumor targets.|||Up-regulated in activated CD8(+) T-cells. Up-regulated upon lipopolysaccharide (LPS) and interferon treatments in macrophages. Up-regulated in CD8(+) T-cell infiltring pancreatic islets of prediabetic nonobese diabetic (NOD) mice (at protein level). Isoform 1 and isoform 2 are up-regulated upon T-cell receptor (TCR) stimulation in CD8(+) T-cells. Isoform 1 is modestly up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon lipopolysaccharide (LPS) in macrophages. Isoform 2 is up-regulated upon poly(I:C) and interleukin IL2 in natural killer (NK) cells. http://togogenome.org/gene/10090:Gp1ba ^@ http://purl.uniprot.org/uniprot/O35930 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.|||Glycocalicin is the product of a proteolytic cleavage/shedding, catalyzed by ADAM17, which releases most of the extracellular domain. Binding sites for vWF and thrombin are in this part of the protein.|||Membrane|||O-glycosylated.|||Platelet activation apparently involves disruption of the macromolecular complex of GP-Ib with the platelet glycoprotein IX (GP-IX) and dissociation of GP-Ib from the actin-binding protein.|||Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage. Interacts with FLNB. Interacts with FLNA (via filamin repeats 4, 9, 12, 17, 19, 21, and 23). http://togogenome.org/gene/10090:Cish ^@ http://purl.uniprot.org/uniprot/Q62225 ^@ Developmental Stage|||Function|||Induction|||Subunit|||Tissue Specificity ^@ By a subset of cytokines including interleukins 2, 3 and 6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO).|||Expressed in kidney, lung and liver. Detected to a lower extent in stomach and heart.|||In the developing brain, expressed at low levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8.|||SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).|||Stably associated with the tyrosine-phosphorylated IL3 receptor beta chain and tyrosine-phosphorylated EPO receptor (EPOR). http://togogenome.org/gene/10090:Slc7a5 ^@ http://purl.uniprot.org/uniprot/Q9Z127 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.|||Cell membrane|||Detected in brain, spleen, liver and testis (at protein level) (PubMed:9915839). Predominantly expressed in the microvessels in the brain parenchyma of the central nervous system. Also detected in the subfornical organ, the subcommissural organ, ventromedial nucleus of the hypothalamus, subgranular zone of the dentate gyrus in hippocampus, ependymal layer of the lateral ventricles, and the olfactory bulb. Very strong expression also seen in testis, ovary, and placenta with weaker expression in spleen, skin, brain, thymus, stomach, lung, heart, kidney, small intestine, uterus and skeletal muscle.|||Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc (PubMed:9915839, PubMed:11011012). Interacts with LAPTM4B; this recruits the heterodimer formed by SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (By similarity).|||Expression induced by concanavalin-A stimulation.|||Leucine uptake was inhibited by ileum, valine histidine and phenylalanine as well as by 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylate (BCH) (a specific inhibitor of system L transport).|||Lysosome membrane|||Strong expression in the liver of 14 dpc embryo. In embryo of 18 dpc expressed strongly in brain, moderate expression in spleen and brain and weak expression in liver.|||The heterodimer with SLC3A2 functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, histidine, met hionine, tryptophan, valine, isoleucine and alanine (By similarity). The heterodimer with SLC3A2 mediates the uptake of L-DOPA and leucine (PubMed:9915839, PubMed:11011012). Functions as an amino acid exchanger (By similarity). May play a role in the transport of L-DOPA across the blood-brain barrier (PubMed:11011012). May act as the major transporter of tyrosine in fibroblasts (By similarity). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier (By similarity). Can mediate the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane. When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation. Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane (By similarity). http://togogenome.org/gene/10090:Orc5 ^@ http://purl.uniprot.org/uniprot/Q9WUV0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORC5 family.|||Chromosome|||Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase.|||Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.|||Multi-mono-ubiquitinated by OBI1; ubiquitination is important for efficient DNA replication origin site activation. Ubiquitination levels are low in mitotic and early G1-phAse cells and are induced in late G1-/early S-phase, peaking in S-phase and decrease toward the end of the cell cycle.|||Nucleus http://togogenome.org/gene/10090:Hnrnph1 ^@ http://purl.uniprot.org/uniprot/O35737|||http://purl.uniprot.org/uniprot/Q3TNG9|||http://purl.uniprot.org/uniprot/Q811L7|||http://purl.uniprot.org/uniprot/Q8C2Q7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Each quasi-RRM repeat bound poly(RG), while only the N-terminal QRRM bound poly(RC) and poly(RU). None of the repeats bound detectable amounts of poly(RA).|||Part of a ternary complex containing FUBP2, PTBP1, PTBP2 and HNRNPH1. Identified in the spliceosome C complex. Interacts with IGF2BP1. Interacts with CUGBP1; the interaction is RNA-dependent. Interacts with MBNL1; the interaction in RNA-independent (By similarity).|||This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Mediates pre-mRNA alternative splicing regulation. Inhibits, together with CUGBP1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast. Binds to the IR RNA. Binds poly(RG) (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Arfgap1 ^@ http://purl.uniprot.org/uniprot/Q9EPJ9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1). Involved in membrane trafficking and /or vesicle transport. Promotes hydrolysis of the ARF1-bound GTP and thus, is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles, a prerequisite for vesicle's fusion with target compartment. Probably regulates ARF1-mediated transport via its interaction with the KDELR proteins and TMED2. Overexpression induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, as when ARF1 is deactivated. Its activity is stimulated by phosphoinosides and inhibited by phosphatidylcholine (By similarity).|||Golgi apparatus|||Interacts with ARF1. Interacts with the COPI coat proteins, KDELR1 and TMED2. It is probably a component of the COPI coat protein complex. The interaction with TMED2 inhibits the GAP activity (By similarity).|||The region downstream of Arf-GAP domain is essential to GAP activity in vivo. This region may be required for its targeting to Golgi membranes (By similarity). http://togogenome.org/gene/10090:Fcrlb ^@ http://purl.uniprot.org/uniprot/Q5DRQ8 ^@ Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum|||Expressed at low levels. Expressed in B-lymphocytes. Detected in spleen, lymph node, kidney, lung and brain.|||Up-regulated upon cell cycle arrest. http://togogenome.org/gene/10090:Ddit4l ^@ http://purl.uniprot.org/uniprot/B2RVG4|||http://purl.uniprot.org/uniprot/Q8VHZ5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DDIT4 family.|||Cytoplasm|||Inhibits cell growth by regulating the TOR signaling pathway upstream of the TSC1-TSC2 complex and downstream of AKT1. http://togogenome.org/gene/10090:Mmp20 ^@ http://purl.uniprot.org/uniprot/P57748 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autoactivates at least at the 106-Asn-|-Tyr-107 site.|||Belongs to the peptidase M10A family.|||Binds 2 Calcium ions per subunit.|||Binds 2 Zn(2+) ions per subunit.|||Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP). May play a central role in tooth enamel formation. Cleaves aggrecan at the '360-Asn-|-Phe-361' site.|||Expressed specifically in the enamel organ.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix http://togogenome.org/gene/10090:Cd80 ^@ http://purl.uniprot.org/uniprot/Q00609 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed between 4 and 12 hours post-activation. Protein was detected at cell surface at 24 hours and it's expression was maximal from 48 to 72 hours post-activation.|||Expressed on activated B-cells, gamma interferon stimulated monocytes and non-circulating B-cell malignancies.|||Involved in the costimulatory signal essential for T lymphocytes activation. T-cell proliferation and cytokine production is induced by the binding of CD28 or CTLA-4 to this receptor.|||Membrane http://togogenome.org/gene/10090:Cul9 ^@ http://purl.uniprot.org/uniprot/S4R1Y1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cullin family.|||Cytoplasm http://togogenome.org/gene/10090:Usp15 ^@ http://purl.uniprot.org/uniprot/Q8R5H1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo. Identified in a complex with the COP9 signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct. Forms a complex with SMURF2 and SMAD7. Interacts with TGFBR1. Interacts with SART3; the interaction is direct. May interact with RNF20 and RNF40. May interact with PRKN. Interacts with INCA1.|||Belongs to the peptidase C19 family.|||Cytoplasm|||Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes. According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal. Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B. Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery. Acts as a negative regulator of antifungal immunity by mediating 'Lys-27'-linked deubiquitination of CARD9, thereby inactivating CARD9.|||Mitochondrion|||Nucleus|||Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome.|||Ubiquitinated, leading to degradation by the proteasome.|||Widely expressed with highest levels in the brain and spleen, and lowest levels in the muscles (at protein level) (PubMed:24852371). In the midbrain, strong expression in neurons including the dopaminergic neurons (at protein level) (PubMed:24852371). Widely expressed with highest levels in testis, heart and liver (PubMed:12532266). http://togogenome.org/gene/10090:Chst8 ^@ http://purl.uniprot.org/uniprot/Q8BQ86 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 2 family.|||Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Required for biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Only active against terminal GalNAcbeta1,GalNAcbeta. Not active toward chondroitin.|||Golgi apparatus membrane|||Strongly expressed in brain. Weakly expressed in lung and kidney. Weakly expressed in pituitary. http://togogenome.org/gene/10090:Exosc6 ^@ http://purl.uniprot.org/uniprot/Q8BTW3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase PH family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Eno4 ^@ http://purl.uniprot.org/uniprot/A0A0J9YUP0|||http://purl.uniprot.org/uniprot/Q8C042 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Although it belongs to the enolase family, Leu-362 is present instead of the conserved Glu which is expected to be an active site residue.|||Belongs to the enolase family.|||Expressed at higher levels in late spermatids than in pachytene spermatocytes.|||Expressed at higher levels in pachytene spermatocytes than in late spermatids.|||Interacts with ENO1 (PubMed:23446454). Isoform 1 and isoform 4 interact with AKAP4 (PubMed:23446454).|||Male mice are infertile and the sperm have significantly reduced motility, ATP levels, and enolase enzymatic activity as well as a structurally abnormal sperm fibrous sheath.|||Required for sperm motility, function and male fertility. May be involved in the normal assembly of the sperm fibrous sheath and provides most of the enolase activity in sperm (PubMed:23446454).|||Synthesized as an approximately 70-kDa precursor, which then undergoes proteolytic cleavage to an approximately 60-kDa enzyme; HOATZ associates directly or indirectly with ENO4 to mediate this process before its transport to mature flagella.|||Testis-specific (PubMed:23446454, PubMed:32248064). Expressed in spermatids and ependyma (at protein level) (PubMed:32248064). http://togogenome.org/gene/10090:Apex1 ^@ http://purl.uniprot.org/uniprot/P28352|||http://purl.uniprot.org/uniprot/Q544Z7 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated on Lys-6 and Lys-7. Acetylation is increased by the transcriptional coactivator EP300 acetyltransferase, genotoxic agents like H(2)O(2) and methyl methanesulfonate (MMS). Acetylation increases its binding affinity to the negative calcium response element (nCaRE) DNA promoter. The acetylated form induces a stronger binding of YBX1 to the Y-box sequence in the MDR1 promoter than the unacetylated form. Deacetylated on lysines. Lys-6 and Lys-7 are deacetylated by SIRT1 (By similarity).|||Belongs to the DNA repair enzymes AP/ExoA family.|||Cleaved at Lys-30 by granzyme A to create the mitochondrial form; leading in reduction of binding to DNA, AP endodeoxyribonuclease activity, redox activation of transcription factors and to enhanced cell death. Cleaved by granzyme K; leading to intracellular ROS accumulation and enhanced cell death after oxidative stress (By similarity).|||Cys-64 and Cys-92 are nitrosylated in response to nitric oxide (NO) and lead to the exposure of the nuclear export signal (NES).|||Cytoplasm|||Endoplasmic reticulum|||Expressed in both resting and stimulated B cells stimulated to switch (at protein level).|||Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends.|||Mitochondrion|||Monomer. Homodimer; disulfide-linked. Component of the SET complex, composed of at least APEX1, SET, ANP32A, HMGB2, NME1 and TREX1. Associates with the dimer XRCC5/XRCC6 in a DNA-dependent manner. Interacts with SIRT1; the interaction is increased in the context of genotoxic stress. Interacts with HDAC1, HDAC2 and HDAC3; the interactions are not dependent on the APEX1 acetylation status. Interacts with XRCC1; the interaction is induced by SIRT1 and increased with the APEX1 acetylated form. Interacts with NPM1 (via N-terminal domain); the interaction is RNA-dependent and decreases in hydrogen peroxide-damaged cells. Interacts (via N-terminus) with YBX1 (via C-terminus); the interaction is increased in presence of APEX1 acetylated at Lys-6 and Lys-7. Interacts with HNRNPL; the interaction is DNA-dependent. Interacts (via N-terminus) with KPNA1 and KPNA2. Interacts with TXN; the interaction stimulates the FOS/JUN AP-1 complex DNA-binding activity in a redox-dependent manner. Interacts with GZMA, KRT8, MDM2, POLB, PRDX6, PRPF19, RPLP0, TOMM20 and WDR77. Binds to CDK5.|||Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA.|||NPM1 stimulates endodeoxyribonuclease activity on double-stranded DNA with AP sites, but inhibits endoribonuclease activity on single-stranded RNA containing AP sites.|||Nucleus|||Nucleus speckle|||Phosphorylated. Phosphorylation by kinase PKC or casein kinase CK2 results in enhanced redox activity that stimulates binding of the FOS/JUN AP-1 complex to its cognate binding site. AP-endodeoxyribonuclease activity is not affected by CK2-mediated phosphorylation (By similarity). Phosphorylation of Thr-232 by CDK5 in response to MPP(+)/MPTP (1-methyl-4-phenylpyridinium) reduces AP-endodeoxyribonuclease activity resulting in accumulation of DNA damage and contributing to neuronal death.|||Probably binds two magnesium or manganese ions per subunit.|||The N-terminus contains the redox activity while the C-terminus exerts the DNA AP-endodeoxyribonuclease activity; both function are independent in their actions. An unconventional mitochondrial targeting sequence (MTS) is harbored within the C-terminus, that appears to be masked by the N-terminal sequence containing the nuclear localization signal (NLS), that probably blocks the interaction between the MTS and Tom proteins (By similarity).|||The specific activity of the cleaved mitochondrial endodeoxyribonuclease appeared to be about 3-fold higher than of the full-length form. Extract of mitochondria, but not of nuclei or cytosol, cleaves recombinant APEX1 to generate a mitochondrial APEX1-sized product (By similarity).|||Ubiquitinated by MDM2; leading to translocation to the cytoplasm and proteasomal degradation.|||nucleolus http://togogenome.org/gene/10090:Orm2 ^@ http://purl.uniprot.org/uniprot/P07361 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Contains a beta-barrel that binds various ligands in its interior.|||Expressed by the liver and secreted in plasma.|||Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain (By similarity). Appears to function in modulating the activity of the immune system during the acute-phase reaction.|||Secreted|||Synthesis is controlled by glucocorticoids, interleukin-1 and interleukin-6, It increases 5- to 50-fold upon inflammation. http://togogenome.org/gene/10090:Zfp967 ^@ http://purl.uniprot.org/uniprot/A2ART1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Shh ^@ http://purl.uniprot.org/uniprot/Q62226 ^@ Caution|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hedgehog family.|||Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.|||By retinoic acid.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in a number of embryonic tissues including the notochord, ventral neural tube, floor plate, lung bud, zone of polarizing activity and posterior distal mesenchyme of limbs. In the adult, expressed in lung and neural retina.|||First detectable during gastrulation.|||Golgi apparatus membrane|||Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (PubMed:18081866). Interacts with BOC and CDON (PubMed:18794898). Interacts with HHIP (By similarity). Interacts with DISP1 via its cholesterol anchor (PubMed:22902404, PubMed:22677548). Interacts with SCUBE2 (PubMed:24522195, PubMed:22677548). Interacts with glypican GPC3 (PubMed:18477453).|||Mice overexpressing Shh display digit duplications in both forelimbs and hindlimbs.|||Multimer.|||N-palmitoylation by HHAT of ShhN is required for sonic hedgehog protein N-product multimerization and full activity (PubMed:11486055, PubMed:15075292). It is a prerequisite for the membrane-proximal positioning and the subsequent shedding of this N-terminal peptide (PubMed:24522195).|||The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (PubMed:7891723, PubMed:7736596, PubMed:8824192). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN)(PubMed:7891723, PubMed:7736596, PubMed:8824192). Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (PubMed:24522195, PubMed:8824192). ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the reticulum endoplasmic (PubMed:21357747).|||The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (PubMed:8824192, PubMed:7891723, PubMed:7736596). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (PubMed:8824192). Both activities occur in the reticulum endoplasmic (PubMed:21357747). Once cleaved, ShhC is degraded in the endoplasmic reticulum (PubMed:21357747).|||The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (PubMed:23118222). The N-terminal palmitoylated peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195).|||The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites (PubMed:11430830, PubMed:24863049). Involved in the patterning of the anterior-posterior axis of the developing limb bud (PubMed:15315762). Essential for axon guidance (PubMed:12679031). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (By similarity).|||The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding)(PubMed:24522195). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate (PubMed:23118222). The cleavage is enhanced by SCUBE2.|||The several steps and mechanisms that permit controlled Shh dispersion and gradient formation remain controversial. The ShhNC C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity resulting in the cleavage and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN). The protein is further modified by covalent addition of palmitate at the N-terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp). ShhNp is firmly tethered to the cell membrane where it forms multimers. Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by proteolytic removal of both terminal lipidated peptides. Once released, the fully processed Shh can signal within embryonic tissues both at short and long-range. http://togogenome.org/gene/10090:Gm10662 ^@ http://purl.uniprot.org/uniprot/Q3UT86 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Apol11a ^@ http://purl.uniprot.org/uniprot/E9PZG0 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Mitf ^@ http://purl.uniprot.org/uniprot/Q08874|||http://purl.uniprot.org/uniprot/Q32MU7 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MiT/TFE family.|||Cytoplasm|||Defects in Mitf are the cause of microphthalmia (mi), a condition characterized by loss of pigmentation; reduced eye size; failure of secondary bone resorption; reduced numbers of mast cells; early onset of deafness, and which gives rise to a number of different phenotypes. Among them, microphthalmia-eyeless white (mi-ew) has a normal appearance at the heterozygous state, but shows white coat; eyes almost absent and eyelids never open at homozygosity. Microphthalmia-black and white spot (mi-bws) is normal at heterozygosity, and presents white spots and black eyes at homozygous state. Microphthalmia-white (mi-wh) has reduced coat color and eye pigmentation; spots on toes, tail and belly; inner ear defects at heterozygosity, and at homozygosity shows white coat; eyes small and inner iris slightly pigmented; spinal ganglia, adrenal medulla and dermis smaller than normal, and inner ear defects. Microphthalmia-vitiligo (mi-vi) has normal phenotype at heterozygosity, but shows gradual depigmentation of coat, skin and eyes; and retinal degeneration at homozygosity. Microphthalmia-spotted (mi-sp) shows normal phenotype; at homozygosity, however, tyrosinase activity in skin is reduced. Microphthalmia-defective irism (mi-di) has reduced retinal pigmentation at heterozygosity and shows white coat; eyes of reduced sized and possible mild osteoporosis at homozygosity. Microphthalmia-cloudy eyed (mi-ce) has a normal appearance at the heterozygous state, but shows white coat; eyes of reduced size and unpigmented at homozygosity. Microphthalmia-red-eyed white (mi-rw) has a normal appearance at the homozygous state, but shows white coat with one or more pigmented spots around the head/and or tail; eyes are small and red at heterozygosity. Microphthalmia-black-eyed white (mi-bw) shows a white coat but normal sized eyes which reamin black at homozygosity.|||Homodimer or heterodimer; dimerization is mediated via the coiled coil region (PubMed:23207919). Efficient DNA binding requires dimerization with another bHLH protein (PubMed:23207919). Binds DNA in the form of homodimer or heterodimer with either TFE3, TFEB or TFEC (PubMed:23207919). Interacts with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD); promoting its recruitment to lysosomal membrane in the presence of nutrients (By similarity). Interacts with KARS1 (PubMed:14975237). Identified in a complex with HINT1 and CTNNB1 (By similarity). Interacts with VSX2 (PubMed:23028343).|||In the adult, expressed at high levels in the heart, skin, skeletal muscle, intestine, stomach, kidney, ovary, lung, spleen and brain. In the embryo, expressed in developing eye, ear, skin and heart. Isoform M is expressed in melanocytes and also in the embryonic and adult heart while isoform A and isoform H are more widely expressed.|||Lysosome membrane|||Nucleus|||The leucine zipper region is part of a larger coiled coil.|||Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis (By similarity). Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoter of pigmentation genes, such as tyrosinase (TYR) (By similarity). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, MITF phosphorylation by MTOR promotes its inactivation (By similarity). Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity (By similarity). Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) (By similarity). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium (By similarity).|||Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation ar Ser-5 by MTOR, leading to its degradation by the proteasome (By similarity). Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome (By similarity). Deubiquitinated by USP13, preventing its degradation (By similarity).|||When nutrients are present, phosphorylation by MTOR at Ser-5 via non-canonical mTORC1 pathway promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (By similarity). Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter (By similarity). Phosphorylation by MARK3/cTAK1 at Ser-280 promotes association with 14-3-3/YWHA adapters and retention in the cytosol (By similarity). Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome (By similarity). Phosphorylated in response to blue light (415nm) (By similarity). http://togogenome.org/gene/10090:Kit ^@ http://purl.uniprot.org/uniprot/P05532 ^@ Activity Regulation|||Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation of isoform 1 and isoform 2. Isoform 1 shows low levels of tyrosine phosphorylation in the absence of added KITLG/SCF, while isoform 2 requires stimulation by KITLG/SCF for phosphorylation (in vitro). Phosphorylation of Tyr-573 is required for interaction with PTPN6/SHP-1. Phosphorylation of Tyr-571 is required for interaction with PTPN11/SHP-2. Phosphorylated tyrosine residues are important for interaction with specific binding partners.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell membrane|||Cytoplasm|||Defects in Kit are the cause of the white-spotting phenotype (W). White-spotting variants induces severe effects on pigmentation, gametogenesis and hematopoiesis. Mice homozygous for W42 die perinatally of macrocytic anemia.|||Isoform 1 and isoform 2 are detected in bone marrow cells, spermatogonia and spermatocytes, but not in round spermatids, elongating spermatids and spermatozoa. Isoform 3 is detected in round spermatids, elongating spermatids and spermatozoa, but not in spermatogonia and spermatocytes (at protein level). Isoform 1 is widely expressed and detected in fetal liver and bone marrow. Isoform 3 is detected in bone marrow cells enriched in hematopoietic stem cells.|||Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with DOK1 and TEC (By similarity). Interacts with the protein kinase FES/FPS. Interacts with PLCG1. Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3 catalytic subunit. Interacts (KITLG/SCF-bound) with IL1RL1. Interacts with IL1RAP (independent of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88.|||Numerous proteins are phosphorylated in response to KIT signaling, but it is not evident to determine which are directly phosphorylated by KIT under in vivo conditions.|||Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation.|||Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1.|||Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation (By similarity). http://togogenome.org/gene/10090:Zfp13 ^@ http://purl.uniprot.org/uniprot/P10754 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expression in the kidney decreases steadily from 3 days until 6 months and then increases slightly at 15 months.|||Nucleus|||Repressed by heat.|||The KRAB domain is required for transcriptional repression.|||Transcriptional repressor that binds to the promoter region of Mpv17l isoform M-LP short and regulates its age-dependent and heat-induced expression (PubMed:20231359). By regulating Mpv17l expression, contributes to the regulation of genes involved in H(2)O(2) metabolism and the mitochondrial apoptotic cascade (PubMed:20231359) (By similarity). http://togogenome.org/gene/10090:Elovl5 ^@ http://purl.uniprot.org/uniprot/Q8BHI7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ELO family. ELOVL5 subfamily.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate in the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators (By similarity). In conditions where the essential linoleic and alpha linoleic fatty acids are lacking it is also involved in the synthesis of Mead acid from oleic acid (PubMed:24184513).|||Endoplasmic reticulum membrane|||dendrite http://togogenome.org/gene/10090:Serpinb1b ^@ http://purl.uniprot.org/uniprot/Q8VHP7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Expressed in brain with lower expression in lung, spleen and testis.|||Monomer. Interacts (via C-terminus) with CASP1 and CASP4 (via CARD domain); these interactions regulate the activity of inflammatory caspases.|||Regulates the activity of the neutrophil proteases. Forms only a stable complex with CTSG/Cathepsin G (PubMed:12189154). During inflammation, limits the activity of inflammatory caspases CASP1 and CASP4 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621). http://togogenome.org/gene/10090:Vmn1r46 ^@ http://purl.uniprot.org/uniprot/Q9EQ45 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Myl3 ^@ http://purl.uniprot.org/uniprot/P09542 ^@ Function|||PTM|||Subunit ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains.|||N-terminus is methylated by METTL11A/NTM1.|||Regulatory light chain of myosin. Does not bind calcium. http://togogenome.org/gene/10090:Ntan1 ^@ http://purl.uniprot.org/uniprot/Q64311 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Monomer.|||N-terminal asparagine deamidase that mediates deamidation of N-terminal asparagine residues to aspartate. Required for the ubiquitin-dependent turnover of intracellular proteins that initiate with Met-Asn. These proteins are acetylated on the retained initiator methionine and can subsequently be modified by the removal of N-acetyl methionine by acylaminoacid hydrolase (AAH). Conversion of the resulting N-terminal asparagine to aspartate by NTAN1/PNAD renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. This enzyme does not act on substrates with internal or C-terminal asparagines and does not act on glutamine residues in any position. http://togogenome.org/gene/10090:Vmn1r1 ^@ http://purl.uniprot.org/uniprot/E9PVR6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rps6kb2 ^@ http://purl.uniprot.org/uniprot/Q9Z1M4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Cytoplasm|||Nucleus|||Phosphorylated and activated by MTOR. Phosphorylation by PKC within the NLS in response to mitogenic stimuli causes cytoplasmic retention.|||Phosphorylates specifically ribosomal protein S6. Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7. http://togogenome.org/gene/10090:Prkd1 ^@ http://purl.uniprot.org/uniprot/Q62101 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-748 and phosphorylation of Ser-744 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-469 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.|||Cell membrane|||Cytoplasm|||Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with MAPK13. Interacts with DAPK1 in an oxidative stress-regulated manner. Interacts with USP28; the interaction induces phosphorylation of USP28 and activated KRAS-mediated stabilization of ZNF304 (By similarity). Interacts with AKAP13 (via C-terminal domain) (PubMed:24161911).|||Phosphorylated at Ser-403 and Ser-407 by MAPK13 during regulation of insulin secretion in pancreatic beta cells (By similarity). Phosphorylated by DAPK1 (By similarity). Phosphorylated at Tyr-93 and by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD (By similarity). Phosphorylated at Ser-916 upon S.enterica infection in macrophages (PubMed:27184844).|||Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:12407104, PubMed:14963034, PubMed:15192707, PubMed:20463010, PubMed:24161911, PubMed:28716882). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS) (PubMed:11784866). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane (PubMed:11239398). May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-469 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion (PubMed:15192707). In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:19029091). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway (PubMed:14963034, PubMed:20463010). Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:24161911). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:28716882). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (By similarity). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (PubMed:27184844).|||trans-Golgi network http://togogenome.org/gene/10090:Nanos1 ^@ http://purl.uniprot.org/uniprot/Q80WY3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nanos family.|||Cytoplasm|||Expressed both maternally and zygotically.|||Expressed in the oocyte. Transiently expressed in eight-cell embryos. At 12.5 dpc, it is re-expressed in the central nervous system and the expression continues in the adult brain, in which the hippocampal formation is the predominant region. Expressed in the seminiferous tubules of mature testis, but not in the primordial germ cells.|||Interacts with PUM2, SNAPIN and CTNNB1. Interacts (via N-terminal region) with CTNND1. Interacts with DDX20 (via N-terminal region) (By similarity).|||May act as a translational repressor which regulates translation of specific mRNAs by forming a complex with PUM2 that associates with the 3'-UTR of mRNA targets. Capable of interfering with the proadhesive and anti-invasive functions of E-cadherin. Up-regulates the production of MMP14 to promote tumor cell invasion (By similarity). Not essential for normal development.|||The N-terminal region and C-terminal zinc-finger RNA-binding domain are both necessary for interaction with SNAPIN.|||The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. It is essential for the translation repression activity of the protein.|||perinuclear region http://togogenome.org/gene/10090:Pop7 ^@ http://purl.uniprot.org/uniprot/Q9DCH2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone-like Alba family.|||Component of nuclear RNase P and RNase MRP complexes. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5. Interacts with SMN1. POP7 forms a heterodimer with RPP25 that binds to the P3 stem loop of the catalytic RNA.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.|||Cytoplasm|||Cytoplasmic granule|||nucleolus http://togogenome.org/gene/10090:Abhd18 ^@ http://purl.uniprot.org/uniprot/Q8C1A9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily.|||Secreted http://togogenome.org/gene/10090:Hoxa1 ^@ http://purl.uniprot.org/uniprot/B9EHK7|||http://purl.uniprot.org/uniprot/Q8BNI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family. Labial subfamily.|||Nucleus http://togogenome.org/gene/10090:Elavl4 ^@ http://purl.uniprot.org/uniprot/Q61701|||http://purl.uniprot.org/uniprot/Q80XH9|||http://purl.uniprot.org/uniprot/Q9CXQ0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14 dpc, expressed in the intermediate zone of the cortex (PubMed:9096138). At 15 dpc, high expression in the neocortex, with decreased expression at postnatal day 7 and in adulthood (PubMed:24599466). At 16 dpc and at birth, expressed in the retina, thalamus, hypothalamus, midbrain, pons, dorsal and ventral spinal cord, and the dorsal root ganglia (PubMed:9096138). At birth, expressed in the nasal epithelium, olfactory bulb, trigeminal ganglia, cerebral cortex, the pyramidal cells of the hippocampus and the sympathetic ganglia (PubMed:9096138). Widely expressed in the cerebellum at postnatal day 9 (PubMed:9096138). Isoform 4: Highly expressed in the brain at 10 dpc to 14 dpc, with decreased expression at 16 dpc and at postnatal day 8 (PubMed:9096138). Isoform 5: Highly expressed in the brain at 10 dpc, with decreased expression at 16 dpc and at postnatal day 8 (PubMed:9096138). Isoform 6: Expressed in the brain at 14 dpc (PubMed:22895702). Isoform 7: Expressed in the brain at 14 dpc (PubMed:9096138). Isoform 8: Expressed in the brain at 14 dpc (PubMed:9096138). Isoform 9: Expressed in the brain at 14 dpc (PubMed:9096138). Isoform 10: Expressed in the brain at 14 dpc, including the amygdala, hippocampus and cerebral cortex, and strong expression in the olfactory bulb and retina (PubMed:22895702). Isoform 11: Expressed in the brain at 14 dpc (PubMed:9096138).|||Belongs to the RRM elav family.|||Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP (PubMed:15086518). Associates with the EIF4F cap-binding complex, composed of EIF4G, EIF4A, EIF4E and PABP (PubMed:20064466). Within the EIF4F cap-binding complex, interacts with EIF4A (PubMed:20064466). Interacts with SMN (via Tudor domain) in an RNA-independent manner; the interaction is required for localization of ELAVL4 to RNA granules (By similarity). Interacts with MAP1 light chain LC1 (via C-terminus); the interaction contributes to the association of ELAVL4 with microtubules (PubMed:21288476). Interacts with MAP1 light chain LC2 (PubMed:21288476).|||Cytoplasm|||Expressed in the brain, including the hippocampus, and in pancreatic beta cells (at protein level) (PubMed:22387028, PubMed:18493953, PubMed:15764704, PubMed:24599466). Expressed in pyramidal neurons of the hippocampal CA3 and CA1 region and in the hilus but not in dentate granule cells (at protein level) (PubMed:15519747). Expressed in the dorsal root ganglion and the spinal cord (at protein level) (PubMed:17035636, PubMed:28111162). Expressed in neural stem and progenitor cells (at protein level) (PubMed:16554442). Expressed in radial glia-like cells and in transient amplifying cells in the subventricular zone (SVZ), and in immature neurons both in the SVZ and the rostral migratory stream as well as in mature neurons in the olfactory bulb (at protein level) (PubMed:26305964). Expressed in testis and in the brain, including the hippocampus, the neocortex and the cerebellum (PubMed:8535975, PubMed:11573004, PubMed:24857657). Expressed in lower- but not upper-layer primary neurons of the mature neocortex, in the hippocampal regions CA1-3 and the dentate gyrus (PubMed:24599466, PubMed:9096138). Expressed in the mitral and granule cells of the olfactory bulb, cerebral cortex, entorhinal cortex, thalamus, medial habenula, amygdala, granule cells of the cerebellum, pons, olivary nucleus, dorsal and ventral spinal cord and in dorsal root ganglia (PubMed:9096138). Expressed in motor neurons (PubMed:21389246). Isoform 4: Expressed in the brain (PubMed:9096138, PubMed:22895702). Isoform 5: Expressed in the brain (PubMed:9096138). Isoform 6: Expressed in the brain (PubMed:22895702). Isoform 7: Expressed in the brain (PubMed:22895702). Isoform 8: Expressed in the brain (PubMed:22895702). Isoform 9: Expressed in the brain (PubMed:22895702). Isoform 10: Expressed in the brain (PubMed:22895702). Isoform 11: Expressed in the brain (PubMed:22895702).|||Methylated by CARM1, which leads to reduced RNA-binding activity and enhanced interaction with SMN (By similarity). Methylation at Arg-248 by CARM1 weakens protective binding to the 3'UTR of CDKN1A mRNA and down-regulates CDKN1A protein expression, thereby maintaining cells in a proliferative state (By similarity). Methylation is inhibited by NGF, which facilitates neurite outgrowth (By similarity).|||Perikaryon|||Produced by alternative initiation.|||Produced by alternative splicing of isoform 1.|||Produced by alternative splicing of isoform 4.|||RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs (PubMed:15764704, PubMed:16554442, PubMed:17035636, PubMed:20064466, PubMed:22387028, PubMed:23383270, PubMed:26305964, PubMed:28111162). Plays a role in the regulation of mRNA stability, alternative splicing and translation (PubMed:15764704, PubMed:23383270, PubMed:26305964, PubMed:28111162). Binds to AU-rich element (ARE) sequences in the 3' untranslated region (3'UTR) of target mRNAs, including GAP43, VEGF, FOS, CDKN1A and ACHE mRNA (By similarity). Many of the target mRNAs are coding for RNA-binding proteins, transcription factors and proteins involved in RNA processing and/or neuronal development and function (PubMed:26305964). By binding to the mRNA 3'UTR, decreases mRNA deadenylation and thereby contributes to the stabilization of mRNA molecules and their protection from decay (By similarity). Also binds to the polyadenylated (poly(A)) tail in the 3'UTR of mRNA, thereby increasing its affinity for mRNA binding (PubMed:20064466). Mainly plays a role in neuron-specific RNA processing by stabilization of mRNAs such as GAP43, ACHE and mRNAs of other neuronal proteins, thereby contributing to the differentiation of neural progenitor cells, nervous system development, learning and memory mechanisms (PubMed:15764704, PubMed:16554442, PubMed:18218628, PubMed:23383270, PubMed:24599466, PubMed:25692578, PubMed:26305964, PubMed:28111162). Involved in the negative regulation of the proliferative activity of neuronal stem cells and in the positive regulation of neuronal differentiation of neural progenitor cells (PubMed:15764704). Promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone of the hippocampus by binding to and stabilizing SATB1 mRNA (PubMed:26305964). Binds and stabilizes MSI1 mRNA in neural stem cells (PubMed:16554442). Exhibits increased binding to ACHE mRNA during neuronal differentiation, thereby stabilizing ACHE mRNA and enhancing its expression (By similarity). Protects CDKN1A mRNA from decay by binding to its 3'-UTR (By similarity). May bind to APP and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization (By similarity). Plays a role in neurite outgrowth and in the establishment and maturation of dendritic arbors, thereby contributing to neocortical and hippocampal circuitry function (PubMed:24599466). Stabilizes GAP43 mRNA and protects it from decay during postembryonic development in the brain (PubMed:28111162). By promoting the stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite outgrowth (By similarity). Binds to BDNF long 3'UTR mRNA, thereby leading to its stabilization and increased dendritic translation after activation of PKC (PubMed:23383270, PubMed:25692578). By increasing translation of BDNF after nerve injury, may contribute to nerve regeneration (PubMed:28111162). Acts as a stabilizing factor by binding to the 3'UTR of NOVA1 mRNA, thereby increasing its translation and enhancing its functional activity in neuron-specific splicing (PubMed:18218628). Stimulates translation of mRNA in a poly(A)- and cap-dependent manner, possibly by associating with the EIF4F cap-binding complex (PubMed:20064466). May also negatively regulate translation by binding to the 5'UTR of Ins2 mRNA, thereby repressing its translation (PubMed:22387028). Upon glucose stimulation, Ins2 mRNA is released from ELAVL4 and translational inhibition is abolished (PubMed:22387028). Also plays a role in the regulation of alternative splicing (PubMed:17035636). May regulate alternative splicing of CALCA pre-mRNA into Calcitonin and Calcitonin gene-related peptide 1 (CGRP) by competing with splicing regulator TIAR for binding to U-rich sequences of CALCA pre-mRNA (PubMed:17035636).|||The RRM 3 domain is required for binding to poly(A) RNA, for the association with polysomes and with the EIF4F cap-binding complex and for the stimulation of translation (PubMed:20064466). The RRM 1 and RRM 2 domains may contribute to polysome association and stimulation of translation (PubMed:20064466).|||Transiently impaired neurite extensions of several cranial nerves, including glossopharyngeal nerve, hypoglossal nerve, trigeminal nerve and acousticofacial nerves in the midembryonic nervous system at 10.5 dpc, however no developmental delays of the nervous system in later-stage embryos at 14 dpc are obvious (PubMed:15764704). By postnatal weeks 4 to 8, 70-80% of the mice exhibit an abnormal clasping reflex of the hind limbs upon being suspended by the tail (PubMed:15764704). Decreased motor coordination, as impaired performance on an accelerating rotarod is observed (PubMed:15764704). Embryonic neural stem cells exhibit enhanced cell renewal capacity and decreased ability to differentiate into neurons (PubMed:15764704). Failure of neural progenitor cells to leave the cell cycle, resulting in increased apoptosis and in reduced production of postmitotic neurons (PubMed:15764704). Increased number of slowly dividing cells in the subventricular zone (PubMed:15764704). High insulin levels in pancreatic beta cells (PubMed:22387028). At 28 dpc, a decreased number of lower layer neocortical neurons is observed and lower layer neocortical neurons and CA3 hippocampal neurons exhibit a decreased dendritic complexity with fewer basal and apical branchpoints, fewer branch endings and shorter basal dendrites (PubMed:24599466). Basal branching deficiency in neocortical lower layer neurons and in hippocampal CA3 neurons persists into adulthood at 90 dpc (PubMed:24599466). Increased time spent in low-energy-expending activities and less in the high-energy activity of locomotion, indicating an anxiety response (PubMed:24599466). Decreased performance in finding a hidden platform in a water bath (Morris water maze test), suggesting difficulty in learning, lack of avoidance of the open arm in a elevated plus maze test, suggesting an aberrant response to anxiety-producing environments, and higher susceptibility to auditory-induced seizures (PubMed:24599466). RNAi-mediated knockdown in the neocortex at 13.5 dpc results in reduced neurite outgrowth (PubMed:24599466). RNAi-mediated knockdown in neural stem/progenitor cells in the adult subventricular zone impairs early neuronal differentiation (PubMed:26305964).|||Up-regulated by glucose and by insulin (PubMed:22387028). Up-regulated after memory training in radial arm maze experiments (PubMed:11573004). Up-regulated after sciatic nerve injury (PubMed:28111162). Up-regulated during adult neuronal stem cell differentiation (PubMed:26305964).|||axon|||dendrite|||growth cone http://togogenome.org/gene/10090:Micu2 ^@ http://purl.uniprot.org/uniprot/Q8CD10 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MICU1 family. MICU2 subfamily.|||Heterodimer; disulfide-linked; heterodimerizes with MICU1 (PubMed:23409044, PubMed:24560927). Interacts with MCU (PubMed:23409044). The heterodimer formed with MICU1 associates with MCU at low calcium concentration and dissociates from MCU at high calcium level (By similarity). Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1.|||Key regulator of mitochondrial calcium uniporter (MCU) required to limit calcium uptake by MCU when cytoplasmic calcium is low (PubMed:23409044, PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulate and inhibit MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU2 acts as a gatekeeper of MCU that senses calcium level via its EF-hand domains: prevents channel opening at resting Ca(2+), avoiding energy dissipation and cell-death triggering (PubMed:24560927).|||Mitochondrion intermembrane space|||Predominantly expressed in stomach, intestine, skeletal muscle, kidney, heart, testis, prostate and uterus.|||The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels (PubMed:24560927). It is unclear which EF-hand binds calcium as none of the 4 EF-hand domains seem to contain a canonical calcium-binding site. http://togogenome.org/gene/10090:Hcls1 ^@ http://purl.uniprot.org/uniprot/P49710 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed only in tissues and cells of hematopoietic origin.|||Interacts (via SH2 domain) with FGR (By similarity). Associates with the SH2 and SH3 domains of LCK. Binding to he LCK SH3 domain occurs constitutively, while binding to the LCK SH2 domain occurs only upon TCR stimulation. A similar binding pattern was observed with LYN, but not with FYN in which the FYN SH2 region associates upon TCR stimulation but the FYN SH3 region does not associate regardless of TCR stimulation. Directly associates with HAX1, through binding to its C-terminal region. Interacts with HS1BP3. Interacts with FES/FPS. Forms a multiprotein complex with LYN and ANKRD54.|||Mitochondrion|||Phosphorylated by LYN, FYN and FGR after cross-linking of surface IgM on B-cells. Phosphorylation by LYN, FYN and FGR requires prior phosphorylation by SYK (By similarity). Binds to LCK in vivo, and is tyrosine phosphorylated upon TCR stimulation. Phosphorylated by FES.|||Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression (By similarity). http://togogenome.org/gene/10090:Mmab ^@ http://purl.uniprot.org/uniprot/D3Z1G7|||http://purl.uniprot.org/uniprot/Q9D273 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Cob(I)alamin adenosyltransferase family.|||Converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), a coenzyme for methylmalonyl-CoA mutase, therefore participates in the final step of the vitamin B12 conversion. Generates adenosylcobalamin (AdoCbl) and directly delivers the cofactor to MUT in a transfer that is stimulated by ATP-binding to MMAB and gated by MMAA.|||Due to intron retention.|||Homotrimer.|||Mitochondrion http://togogenome.org/gene/10090:Tas2r104 ^@ http://purl.uniprot.org/uniprot/Q7M723 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Cpm ^@ http://purl.uniprot.org/uniprot/Q80V42 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins (By similarity). http://togogenome.org/gene/10090:Pdcd1 ^@ http://purl.uniprot.org/uniprot/Q02242 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Induced at programmed cell death.|||Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11698646, PubMed:11209085, PubMed:21300912). Delivers inhibitory signals upon binding to ligands, such as CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:11015443, PubMed:11224527, PubMed:22641383, PubMed:18287011, PubMed:18641123). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (PubMed:22641383). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:11698646, PubMed:22641383). The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (By similarity).|||Mice grow and develop normally but exhibit splenomegaly, selective augmentation of IgG3 antibody response to a T-independent type II antigen, and enhanced proliferative responses of B-cells and myeloid cells by anti-IgM and granulocyte colony-stimulating factor stimulation (PubMed:9796923). Mice are prone to development of autoimmune diseases (PubMed:10485649, PubMed:11209085). In a C57BL/6J background, mice spontaneously develop lupus-like autoimmune phenotypes, characterized by proliferative arthritis and glomerulonephritis with predominant IgG3 deposition (PubMed:10485649). In a BALB/c background, mice develop autoimmune dilated cardiomyopathy with severely impaired contraction, and two-third of mice die by congestive heart failure before 30 weeks of age (PubMed:11209085). Mice lacking both Lag3 and Pdcd1/PD-1 die of severe myocarditis before 10 weeks of age in BALB/c mice (PubMed:21300912).|||Monomer (PubMed:15030777, PubMed:18287011, PubMed:18641123). Interacts with CD274/PDCD1L1 (PubMed:18287011). Interacts with CD273/PDCD1LG2 (PubMed:18641123). Interacts with FBXO38; leading to ubiquitination and degradation by the proteasome (By similarity).|||Thymus-specific.|||Tyrosine phosphorylated at Tyr-225 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding (PubMed:11698646, PubMed:22641383). Phosphorylation at Tyr-248 promotes the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:22641383).|||Ubiquitinated at Lys-235 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains. http://togogenome.org/gene/10090:Ywhab ^@ http://purl.uniprot.org/uniprot/A2A5N2|||http://purl.uniprot.org/uniprot/Q9CQV8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13.|||Belongs to the 14-3-3 family.|||Cytoplasm|||Homodimer (By similarity). Interacts with SAMSN1 and PRKCE (PubMed:18604201, PubMed:20478393). Interacts with AKAP13. Interacts with SSH1 and TORC2/CRTC2. Interacts with ABL1; the interaction results in cytoplasmic location of ABL1 and inhibition of cABL-mediated apoptosis. Interacts with ROR2 (dimer); the interaction results in phosphorylation of YWHAB on tyrosine residues. Interacts with GAB2. Interacts with YAP1 (phosphorylated form). Interacts with the phosphorylated (by AKT1) form of SRPK2. Interacts with PKA-phosphorylated AANAT. Interacts with MYO1C. Interacts with SIRT2 (By similarity). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B. Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By similarity). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (By similarity). Interacts with SLITRK1 (By similarity). Interacts with SYNPO2 (phosphorylated form); YWHAB competes with ACTN2 for interaction with SYNPO2 (PubMed:15883195). Interacts with RIPOR2 (via phosphorylated form); this interaction occurs in a chemokine-dependent manner and does not compete for binding of RIPOR2 with RHOA nor blocks inhibition of RIPOR2-mediated RHOA activity (By similarity). Interacts with MARK2 and MARK3 (By similarity). Interacts with TESK1; the interaction is dependent on the phosphorylation of TESK1 'Ser-439' and inhibits TESK1 kinase activity (By similarity). Interacts with MEFV (By similarity). Interacts with HDAC4 (By similarity). Interacts with ADAM22 (via C-terminus) (By similarity).|||Isoform Short contains a N-acetylmethionine at position 1.|||Isoform alpha differs from isoform beta in being phosphorylated (By similarity). Phosphorylated on Ser-60 by protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion.|||Melanosome http://togogenome.org/gene/10090:Lama3 ^@ http://purl.uniprot.org/uniprot/Q61789 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basal membrane of the upper alimentary tract and urinary and nasal epithelia, salivary glands and teeth (both variants). Isoform A is predominantly expressed in skin, hair follicles and developing neurons of the trigeminal ganglion. Isoform B was found in bronchi, alveoli, stomach, intestinal crypts, whisker pads, CNS, telencephalic neuroectoderm, thalamus, Rathke pouch and periventricular subependymal germinal layer.|||Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Domains IV and G are globular.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-3 is a subunit of laminin-5 (laminin-332 or epiligrin/kalinin/nicein), laminin-6 (laminin-311 or K-laminin) and laminin-7 (laminin-321 or KS-laminin).|||Laminin-5 is thought to be involved in (1) cell adhesion via integrin alpha-3/beta-1 in focal adhesion and integrin alpha-6/beta-4 in hemidesmosomes, (2) signal transduction via tyrosine phosphorylation of pp125-FAK and p80, (3) differentiation of keratinocytes.|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Micu3 ^@ http://purl.uniprot.org/uniprot/Q9CTY5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MICU1 family. MICU3 subfamily.|||Binds calcium.|||May play a role in mitochondrial calcium uptake.|||Membrane|||Mitochondrion|||Predominantly expressed in skeletal muscle and central nervous system. http://togogenome.org/gene/10090:Tram1l1 ^@ http://purl.uniprot.org/uniprot/Q8QZR0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAM family.|||Endoplasmic reticulum membrane|||Stimulatory or required for the translocation of secretory proteins across the ER membrane. http://togogenome.org/gene/10090:Fgd1 ^@ http://purl.uniprot.org/uniprot/A2ALP5|||http://purl.uniprot.org/uniprot/P52734|||http://purl.uniprot.org/uniprot/Q3UG32 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape.|||Cytoplasm|||Interacts with DBNL/ABP1 and CTTN. Binds CDC42 (By similarity). May interact with CCPG1.|||The DH domain is involved in interaction with CCPG1.|||cytoskeleton|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Pla2g2d ^@ http://purl.uniprot.org/uniprot/Q3TYT9|||http://purl.uniprot.org/uniprot/Q9WVF6 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Cell membrane|||Cytoplasm|||Highly expressed in secondary lymphoid tissues, spleen and lymph nodes. Expressed at a lesser extent in thymus (PubMed:11196711, PubMed:10455175, PubMed:10531313, PubMed:23690440). Expressed in CD4-positive, IL2RA/CD25-positive, FOXP3-positive Tregs (at protein level) (PubMed:19564598, PubMed:23690440). Expressed in myeloid cell subsets resident in spleen and lymph nodes, ITGAX/CD11C-positive dendritic cells and macrophages (at protein level). Enriched in CD4-positive, ITGAM/CD11B-positive dendritic cell subset (PubMed:19564598, PubMed:23690440). Expressed in pulmonary ITGAX/CD11C-positive dendritic cell subset (at protein level) (PubMed:26392224).|||Knockout mice are born at the expected Mendelian rate and have normal embryonic and postnatal development (PubMed:23690440). They are susceptible to acute and chronic inflammatory reactions and resistant to tumorigenesis. In a model of hapten-induced contact hypersensitivity, mutant mice show an enhanced T-helper 1 immune response in skin lymph nodes at sensitization phase followed by delayed inflammation resolution with more severe ear swelling, epidermal hyperplasia, and inflammatory cell infiltration at elicitation phase (PubMed:23690440, PubMed:27226632). In a psoriasis model, mutant mice show enhanced T-helper 17 immune response and epidermal hyperplasia associated with decreased synthesis of omega-3 PUFAs (PubMed:27226632). In a model of chemically-induced skin carcinogenesis, mutant mice show resistance to cutaneous papilloma formation (PubMed:27226632). In response to SARS-CoV infection, mutant middle-aged (10-13 month old) mice mount a potent antiviral T cell response, resulting in more rapid virus clearance and significantly decreased mortality compared with wild-type ones. This represents a relevant model for SARS-CoV increased susceptibility with aging in human (PubMed:26392224).|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets extracellular lipids, exerting anti-inflammatory and immunosuppressive functions (PubMed:10531313, PubMed:23690440, PubMed:26392224, PubMed:10455175). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (By similarity). In draining lymph nodes, selectively hydrolyzes diacyl and alkenyl forms of phosphatidylethanolamines, releasing omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoate and docosahexaenoate that are precursors of the anti-inflammatory lipid mediators, resolvins (PubMed:23690440). During the resolution phase of acute inflammation drives docosahexaenoate-derived resolvin D1 synthesis, which suppresses dendritic cell activation and T-helper 1 immune response (PubMed:23690440, PubMed:27226632). May act in an autocrine and paracrine manner. Via a mechanism independent of its catalytic activity, promotes differentiation of regulatory T cells (Tregs) and participates in the maintenance of immune tolerance (PubMed:19564598). May contribute to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541).|||Undetectable in embryonic spleens. Weak expression is detected the first week after birth, with further increase to normal levels by 4-6 weeks after birth.|||Up-regulated in thymus upon endotoxin challenge (PubMed:10455175). Up-regulated during Treg differention in response to TGFB1 (PubMed:19564598). Up-regulated in pulmonary ITGAX/CD11C-positive dendritic cell subset upon chronic oxidative stress associated with aging (PubMed:26392224). http://togogenome.org/gene/10090:Btf3 ^@ http://purl.uniprot.org/uniprot/Q3UJR8|||http://purl.uniprot.org/uniprot/Q64152 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAC-beta family.|||Cytoplasm|||Nucleus|||Part of the nascent polypeptide-associated complex (NAC), which is a heterodimer of NACA and BTF3 (via NAC-A/B domains). NAC associates with ribosomes through the BTF3/NACB subunit. Both subunits can contact nascent polypeptide chains (By similarity).|||When associated with NACA, prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. BTF3 is also a general transcription factor that can form a stable complex with RNA polymerase II. Required for the initiation of transcription (By similarity). http://togogenome.org/gene/10090:Mapkapk2 ^@ http://purl.uniprot.org/uniprot/P49138|||http://purl.uniprot.org/uniprot/Q3U2P8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Heterodimer with p38-alpha/MAPK14; this heterodimer forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with PHC2. Interacts with HSF1.|||No visible phenotype. Mice are fertile and do not exhibit behavioral phenotype. Mice show decreased production of inflammatory cytokines such as TNF and IL6 upon LPS-stimulation. Impaired cytokine production make mice less sensitive to LPS-induced endotoxic shock, but more susceptible to bacterial infection. Moreover, the amount of MAP kinase p38 is significantly reduced in cells and tissues. Mice lacking both Mapkapk2 and Mapkapk3 show further reduction of TNF production.|||Nucleus|||Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-208; Ser-258 and Thr-320.|||Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (By similarity). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress following ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (By similarity). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.|||Sumoylation inhibits the protein kinase activity.|||Ubiquitously expressed (at protein level). http://togogenome.org/gene/10090:Ndufv2 ^@ http://purl.uniprot.org/uniprot/Q9D6J6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I 24 kDa subunit family.|||Binds 1 [2Fe-2S] cluster.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme (By similarity).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Msi1 ^@ http://purl.uniprot.org/uniprot/Q61474 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Musashi family.|||Cytoplasm|||Expressed in neural stem and progenitor cells (at protein level) (PubMed:16554442). Detected in olfactory bulb, brain stem, small intestine, and at low levels in brain cortex, hippocampus and ovary (PubMed:8660864). Detected in neural progenitor cells, including neural stem cells (PubMed:8660864).|||Highly expressed in embryonic brain at day 12. Expressed at intermediate levels during the rest of embryonic development and in newborns up to day 3. After this expression decreases and stabilizes at low levels of expression around day 13.|||Nucleus|||RNA binding protein that regulates the expression of target mRNAs at the translation level. Regulates expression of the NOTCH1 antagonist NUMB. Binds RNA containing the sequence 5'-GUUAGUUAGUUAGUU-3' and other sequences containing the pattern 5'-[GA]U(1-3)AGU-3'. May play a role in the proliferation and maintenance of stem cells in the central nervous system.|||The first RNA recognition motif binds more strongly to RNA compared to the second one. http://togogenome.org/gene/10090:Usp24 ^@ http://purl.uniprot.org/uniprot/B1AY13 ^@ Function|||Similarity ^@ Belongs to the peptidase C19 family.|||Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains. Deubiquitinates DDB2, preventing its proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Rims2 ^@ http://purl.uniprot.org/uniprot/Q9EQZ7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in testis, pituitary and an insulinoma cell line. Detected at low levels in cerebellar cortex.|||Interacts with TSPOAP1 and RIMBP2. Interacts with PPFIA3 and PPFIA4. Interacts via its zinc finger with the first C2 domain of UNC13A. Forms a complex consisting of UNC13A, RIMS2 and RAB3A (By similarity). Heterodimer with PCLO. Part of a ternary complex involving PCLO and EPAC2. Interacts with RAB3A and RAB3B that have been activated by GTP-binding. Interacts with RAB3C, RAB3D and RAB26.|||Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (By similarity).|||synaptosome http://togogenome.org/gene/10090:Gpha2 ^@ http://purl.uniprot.org/uniprot/A2RSW3|||http://purl.uniprot.org/uniprot/Q925Q5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycoprotein hormones subunit alpha family.|||Functions as a heterodimeric glycoprotein hormone with GPHB5 able to bind and activate the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production. Plays a central role in controlling thyroid cell metabolism.|||Heterodimer with GPHB5; this heterodimer interacts with thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP production.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:St8sia2 ^@ http://purl.uniprot.org/uniprot/O35696 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||May transfer sialic acid through alpha-2,8-linkages to the alpha-2,3-linked and alpha-2,6-linked sialic acid of N-linked oligosaccharides of glycoproteins and may be involved in PSA (polysialic acid) expression. http://togogenome.org/gene/10090:Wnt3a ^@ http://purl.uniprot.org/uniprot/P27467 ^@ Caution|||Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A palmitoylation site was proposed at Cys-77, but it was later shown that this cysteine is engaged in a disulfide bond.|||Belongs to the Wnt family.|||Detected in the dorsal primitive streak region at 8.5 dpc. Detected in the tailbud region and in the developing central nervous system (CNS) at 9.5 dpc.|||Disulfide bonds have critical and distinct roles in secretion and activity. Loss of each conserved cysteine in WNT3A results in high molecular weight oxidized Wnt oligomers, which are formed through inter-Wnt disulfide bonding.|||Dorsal portion of the neural tube (developing roof plate), and mesenchyme tissue surrounding the umbilical veins.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720). Homooligomer; disulfide-linked, leading to inactivation (PubMed:25771893). Interacts with APCDD1 and WLS. Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly in the complex with LRP6 (By similarity). Interacts with PORCN (PubMed:10866835). Interacts with glypican GPC3 (By similarity). Interacts with PKD1 (via extracellular domain) (By similarity).|||Gene targeting that leads to the production of a truncated mRNA causes full embryonic lethality at 10.5 to 12.5 dpc.|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:26902720). Required for normal embryonic mesoderm development and formation of caudal somites (PubMed:8299937). Required for normal morphogenesis of the developing neural tube (PubMed:8299937). Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro) (PubMed:26902720).|||Palmitoleoylation by PORCN is required for efficient binding to frizzled receptors. Palmitoleoylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoleoylated WNT3A from WLS in secretory vesicles (PubMed:17141155, PubMed:24798332). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway, possibly by promoting disulfide bond formation and oligomerization (PubMed:25771893).|||Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT3A.|||Secreted|||The formation of disulfide-linked oligomers may be an artifact that occurs upon heterologous expression in vitro (PubMed:25771893, PubMed:26902720). Formation of disulfide-linked oligomers is not observed when the protein is coexpressed with AFM (PubMed:26902720).|||extracellular matrix http://togogenome.org/gene/10090:Or4e2 ^@ http://purl.uniprot.org/uniprot/Q7TQQ0 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Copper binding enhances receptor activity in response to odorant binding.|||Detected at very low levels at 18 dpc and increased to its maximum level of expression by 7 days after birth in olfactory sensory neurons of the septal organ.|||Expressed in olfactory epithelium, specifically in the olfactory sensory neurons of the septal organ.|||Olfactory receptor that is activated by the binding of organosulfur odorants with thioether groups such as (methylthio)methanethiol (MTMT) and bis(methylthiomethyl) disulfide (PubMed:22328155, PubMed:25185561, PubMed:25901328, PubMed:29659735). Also binds odorants cis-cyclooctene and tert-butyl mercaptan (PubMed:27019154). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (Potential). http://togogenome.org/gene/10090:Prss22 ^@ http://purl.uniprot.org/uniprot/Q9ER10 ^@ Similarity ^@ Belongs to the peptidase S1 family. http://togogenome.org/gene/10090:Tmem216 ^@ http://purl.uniprot.org/uniprot/Q9CQC4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Membrane|||Part of the tectonic-like complex (also named B9 complex) (PubMed:21725307). Interacts with TMEM107 (By similarity).|||Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition.|||cilium basal body http://togogenome.org/gene/10090:Nrg3 ^@ http://purl.uniprot.org/uniprot/E9Q396|||http://purl.uniprot.org/uniprot/G3V023|||http://purl.uniprot.org/uniprot/O35181 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neuregulin family.|||Cell membrane|||Detected as early as 11 dpc. At 13 dpc detected mainly in the nervous system. At 16 dpc, detected in the brain, spinal cord, trigeminal, vestibular-cochlear, and spinal ganglia. In adults, expressed in spinal cord, and numerous brain regions.|||Direct ligand for the ERBB4 tyrosine kinase receptor. Binding results in ligand-stimulated tyrosine phosphorylation and activation of the receptor. Does not bind to the EGF receptor, ERBB2 or ERBB3 receptors.|||ERBB receptor binding is elicited entirely by the EGF-like domain.|||Expressed in sympathetic, motor, and sensory neurons.|||Extensive glycosylation precedes the proteolytic cleavage.|||Interacts with ERBB4.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.|||Secreted|||The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity). http://togogenome.org/gene/10090:Mettl22 ^@ http://purl.uniprot.org/uniprot/Q8R1C6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METTL22 family.|||Interacts with members of the heat shock protein 90 and 70 families; these proteins probably are methylation substrates.|||Nucleus|||Protein N-lysine methyltransferase. Trimethylates KIN at Lys-135 (in vitro). http://togogenome.org/gene/10090:Ttll3 ^@ http://purl.uniprot.org/uniprot/A4Q9E5 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Arg-482 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in brain and testis (PubMed:17499049, PubMed:25180231). Expressed in heart, kidney, liver, lung, muscle, spleen, trachea and colon (PubMed:17499049, PubMed:25180231, PubMed:33414192). Expressed in sperm flagellum (PubMed:33414192). In the brain, specifically expressed in ependymal cilia (PubMed:23897886).|||In knockout mice, colon epithelium shows absence of glycylation, a reduced number of primary cilia accompanied by an increased rate of cell division (PubMed:25180231). Knockout mice show no visible motile ependymal cilia phenotype (PubMed:23897886). Simultaneous TTLL3 and TTLL8 knockout mice are subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells (PubMed:33414192). Simultaneous TTLL3 and TTLL8 knockout mice show no visible motile ependymal cilia phenotype in brain ventricles (PubMed:33414192).|||Monoglycylase which modifies alpha- and beta-tubulin, adding a single glycine on the gamma-carboxyl groups of specific glutamate residues to generate monoglycine side chains within the C-terminal tail of tubulin (PubMed:19524510). Not involved in elongation step of the polyglycylation reaction (PubMed:19524510). Preferentially glycylates a beta-tail peptide over the alpha-tail, although shifts its preference toward alpha-tail as beta-tail glutamylation increases (By similarity). Competes with polyglutamylases for modification site on beta-tubulin substrate, thereby creating an anticorrelation between glycylation and glutamylation reactions (PubMed:33414192). Together with TTLL8, mediates microtubule glycylation of primary and motile cilia, which is essential for their stability and maintenance (PubMed:23897886, PubMed:25180231). Involved in microtubule glycylation of primary cilia in colon which controls cell proliferation of epithelial cells and plays an essential role in colon cancer development (PubMed:25180231). Together with TTLL8, glycylates sperm flagella which regulates axonemal dynein motor activity, thereby controlling flagellar beat, directional sperm swimming and male fertility (PubMed:33414192).|||TTLL3 and TTLL8 monoglycylase-mediated glycylation of tubulin was initially reported to play a role in ependymal motile ciliary maintenance (PubMed:23897886). However, contradictory results were later observed (PubMed:33414192).|||Two conserved structural elements specific among monoglycylases, IS1 and IS2, are involved in glycyl chains initiation. Two conserved structural interfaces likely constitute the binding platforms for tubulin tail and microtubule.|||cilium|||cilium axoneme|||cytoskeleton|||flagellum axoneme http://togogenome.org/gene/10090:Epb42 ^@ http://purl.uniprot.org/uniprot/P49222 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transglutaminase superfamily. Transglutaminase family.|||Cell membrane|||Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with SLC4A1 (via the cytoplasmic domain); this interaction is mediated by the SLC4A1 Band 3-I dimer. Interacts with ANK1 (via ANK 1-13 repeats). Interacts with AQP1 (via the C-terminal).|||Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.|||The substitution of an Ala for a Cys in the active site may be responsible for the lack of transglutaminase activity of band 4.2.|||Was originally thought to be pallidin.|||cytoskeleton http://togogenome.org/gene/10090:Atpaf2 ^@ http://purl.uniprot.org/uniprot/Q91YY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP12 family.|||Interacts with ATP5F1A. Interacts with FMC1.|||May play a role in the assembly of the F1 component of the mitochondrial ATP synthase (ATPase).|||Mitochondrion http://togogenome.org/gene/10090:Alb ^@ http://purl.uniprot.org/uniprot/P07724|||http://purl.uniprot.org/uniprot/Q546G4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ALB/AFP/VDB family.|||Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (By similarity). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (By similarity). Does not prevent iron uptake by the bacterial siderophore aerobactin (By similarity).|||Interacts with FCGRT; this interaction regulates ALB homeostasis (By similarity). Interacts with TASOR (PubMed:31112734). In plasma, occurs in a covalently-linked complex with chromophore-bound alpha-1-microglobulin; this interaction does not prevent fatty acid binding to ALB.|||Phosphorylated by FAM20C in the extracellular medium.|||Plasma. Expressed in the granular cells within the cerebellum (PubMed:31112734).|||Secreted http://togogenome.org/gene/10090:Pnpo ^@ http://purl.uniprot.org/uniprot/Q91XF0 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the pyridoxamine 5'-phosphate oxidase family.|||Binds 1 FMN per subunit.|||Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP).|||Homodimer. http://togogenome.org/gene/10090:Snip1 ^@ http://purl.uniprot.org/uniprot/Q8BIZ6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of activated spliceosome complexes. Binds SMAD4 and CREBBP/EP300. Component of the minor spliceosome, which splices U12-type introns (By similarity). Binds the SMAD1/OAZ1/PSMB4 complex. Interacts with DROSHA and SMARCA4. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN.|||Degraded by the proteasome upon binding to the SMAD1/OAZ1/PSMB4 complex.|||Nucleus|||Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). Down-regulates NF-kappa-B signaling by competing with RELA for CREBBP/EP300 binding. Involved in the microRNA (miRNA) biogenesis. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. http://togogenome.org/gene/10090:Msra ^@ http://purl.uniprot.org/uniprot/A0A1B0GT40|||http://purl.uniprot.org/uniprot/Q9D6Y7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MsrA Met sulfoxide reductase family.|||Cytoplasm|||Cytoplasmic. Produced by alternative initiation.|||Has an important function as a repair enzyme for proteins that have been inactivated by oxidation. Catalyzes the reversible oxidation-reduction of methionine sulfoxide in proteins to methionine.|||Membrane|||Mitochondrial.|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Hmgn2 ^@ http://purl.uniprot.org/uniprot/P09602|||http://purl.uniprot.org/uniprot/Q5BL14 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HMGN family.|||Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation (By similarity).|||Cytoplasm|||Nucleus|||Phosphorylation favors cytoplasmic localization. http://togogenome.org/gene/10090:Slc36a3 ^@ http://purl.uniprot.org/uniprot/Q811P0 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Membrane|||Specifically expressed in testis. http://togogenome.org/gene/10090:Mbtps2 ^@ http://purl.uniprot.org/uniprot/Q8CHX6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M50A family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Golgi apparatus membrane|||Membrane|||Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2. Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription. Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Involved in intramembrane proteolysis during bone formation. In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the second step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression. http://togogenome.org/gene/10090:Nfkbil1 ^@ http://purl.uniprot.org/uniprot/O88995 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ High expression found in heart muscle, liver, kidney and skin. Not detected in spleen, lung and brain.|||Interacts with CACTIN (via N-terminal domain); the interaction occurs in a pro-inflammatory-independent manner.|||Involved in the regulation of innate immune response. Acts as negative regulator of Toll-like receptor and interferon-regulatory factor (IRF) signaling pathways. Contributes to the negative regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous pro-inflammatory stimuli (By similarity).|||Nucleus http://togogenome.org/gene/10090:Abcb8 ^@ http://purl.uniprot.org/uniprot/Q9CXJ4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-binding subunit of the mitochondrial potassium channel located in the mitochondrial inner membrane (By similarity). Together with CCDC51/MITOK, forms a protein complex localized in the mitochondria that mediates ATP-dependent potassium currents across the inner membrane (that is, mitoK(ATP) channel) (By similarity). Plays a role in mitochondrial iron transport (PubMed:22375032). Required for maintenance of normal cardiac function, possibly by influencing mitochondrial iron export and regulating the maturation of cytosolic iron sulfur cluster-containing enzymes (PubMed:22375032).|||Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.|||Channel activity inhibited by ATP via ABCB8/MITOSUR subunit.|||Conditional knockout in heart results in a severe cardiomyopathy and mitochondrial iron accumulation.|||Mitochondrion inner membrane|||The mitochondrial potassium channel (mitoK(ATP)) is composed of 4 subunits of CCDC51/MITOK and 4 subunits of ABCB8/MITOSUR (By similarity). Interacts with PAAT (By similarity). Interacts with NRP1; NRP1 regulates ABCB8/MITOSUR protein levels in mitochondria (By similarity). http://togogenome.org/gene/10090:Mrpl43 ^@ http://purl.uniprot.org/uniprot/Q5RL20 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrion-specific ribosomal protein mL43 family.|||Mitochondrion http://togogenome.org/gene/10090:Npy ^@ http://purl.uniprot.org/uniprot/P57774 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NPY family.|||NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.|||One of the most abundant peptides in the nervous system. Also found in some chromaffin cells of the adrenal medulla.|||Secreted|||The neuropeptide Y form is cleaved at Pro-30 by the prolyl endopeptidase FAP (seprase) activity (in vitro).|||neuronal dense core vesicle http://togogenome.org/gene/10090:Fgf7 ^@ http://purl.uniprot.org/uniprot/P36363|||http://purl.uniprot.org/uniprot/Q544I6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Interacts with FGFBP1. Interacts with FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. Growth factor active on keratinocytes. Possible major paracrine effector of normal epithelial cell proliferation (By similarity).|||Secreted http://togogenome.org/gene/10090:Slc24a5 ^@ http://purl.uniprot.org/uniprot/A2ATP8|||http://purl.uniprot.org/uniprot/Q8C261 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.|||Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+). Involved in pigmentation, possibly by participating in ion transport in melanosomes. Predominant sodium-calcium exchanger in melanocytes.|||Highly expressed in melanin-producing cells such as skin and eye compared to other tissues. Strongly overexpressed in melanoma cell lines. Expressed in dental tissues.|||Melanosome|||Membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Col15a1 ^@ http://purl.uniprot.org/uniprot/O35206 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the multiplexin collagen family.|||Detected at low levels from day 7 to 11 of embryonic development. Levels are much increased and remain high from day 15 to 17.|||Detected in testis, brain, heart, kidney, skeletal muscle and skin (at protein level). Detected in heart and skeletal muscle.|||Interacts moderately with EFEMP2.|||O-glycosylated; contains chondroitin sulfate.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Restin potently inhibits angiogenesis.|||Secreted|||Structural protein that stabilizes microvessels and muscle cells, both in heart and in skeletal muscle.|||The name Restin has also been used for CAP-Gly domain-containing linker protein 1 the product of the CLIP1 gene.|||Trimer; disulfide-linked.|||extracellular matrix http://togogenome.org/gene/10090:Or1a1 ^@ http://purl.uniprot.org/uniprot/Q7TRX2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Kdelr1 ^@ http://purl.uniprot.org/uniprot/Q99JH8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ERD2 family.|||COPI-coated vesicle membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||Phosphorylation by PKA at Ser-209 is required for endoplasmic reticulum retention function.|||Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum.|||Upon ligand binding the receptor oligomerizes and interacts with components of the transport machinery such as ARFGAP1 and ARF1. http://togogenome.org/gene/10090:Hsbp1l1 ^@ http://purl.uniprot.org/uniprot/B2RXB2 ^@ Similarity ^@ Belongs to the HSBP1 family. http://togogenome.org/gene/10090:H2-M5 ^@ http://purl.uniprot.org/uniprot/A7VMS3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Wdr93 ^@ http://purl.uniprot.org/uniprot/Q402B2 ^@ Tissue Specificity ^@ Testis-specific. Expressed in spermatogonia, spermatocytes and spermatids. http://togogenome.org/gene/10090:Stac2 ^@ http://purl.uniprot.org/uniprot/Q8R1B0 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in cerebellum, forebrain and midbrain, and in the eye.|||Interacts (via SH3 domains) with CACNA1S (PubMed:29467163). Interacts (via SH3 domains) with CACNA1C (PubMed:29363593). Has much lower affinity for CACNA1C than for CACNA1S (By similarity).|||Plays a redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity (PubMed:29467163). Slows down the inactivation rate of the calcium channel CACNA1C (PubMed:25548159, PubMed:29363593).|||Up-regulated in cerebral ischemia.|||cytosol|||sarcolemma http://togogenome.org/gene/10090:Prdm14 ^@ http://purl.uniprot.org/uniprot/E9Q3T6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 3.5 dpc, weak and transient expression in the inner cell mass cells of blastocysts. This expression disappears by 5.5 dpc. Expression starts again in committed PGCs around 6.5 dpc in the extraembryonic mesoderm contiguous from the most proximal epiblast (at protein level). Expression persists specifically in PGCs until about 13.5-14.5 dpc both in females and males.|||Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Interacts with CBFA2T2.|||Mutant mice are born with an expected Mendelian ratio and looked grossly normal. However, both females and males are sterile, ovaries and testes being completely devoid of germ cells.|||Nucleus|||Restricted to embryonic stem cells and primordial germ cells. Not detected in epiblast-derived stem cells.|||Transcription factor that has both positive and negative roles on transcription (By similarity). Plays a role in cellular pluripotency. Essential for germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression. Its association with CBFA2T2 is required for the functions in pluripotency and germ cell formation. http://togogenome.org/gene/10090:Ccdc86 ^@ http://purl.uniprot.org/uniprot/Q9JJ89 ^@ Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ By interleukin-3 (IL3).|||Citrullinated by PADI4.|||Highly expressed in testis. Also expressed in heart, liver, kidney.|||Nucleus http://togogenome.org/gene/10090:Dennd2d ^@ http://purl.uniprot.org/uniprot/Q91VV4 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity). http://togogenome.org/gene/10090:Erp44 ^@ http://purl.uniprot.org/uniprot/Q9D1Q6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum lumen|||Forms mixed disulfides with both ERO1A and ERO1B and cargo folding intermediates; the interactions with ERO1A and ERO1B result in their retention in the endoplasmic reticulum (By similarity). Directly interacts with ITPR1 in a pH-, redox state- and calcium-dependent manner, but not with ITPR2 or ITPR3 (PubMed:15652484). The strength of this interaction inversely correlates with calcium concentration (PubMed:15652484).|||Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1A and ERO1B in the endoplasmic reticulum.|||Widely expressed. http://togogenome.org/gene/10090:Tfcp2l1 ^@ http://purl.uniprot.org/uniprot/Q3UNW5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Approximately half of the mutant mice die before weaning and show growth retardation during early postnatal stages. Mice display defects in the morphology of the submandibular ducts, abnormalities in the maturation of renal tubules and abnormal composition of saliva and urine (PubMed:17079272). Leads to a decrease in the expression of pluripotency genes (Nanog, Oct4, Sox2 and Esrrb), while resulted in up-regulation of some endoderm (Sox17, Gata4 and Gata6), mesoderm (T and Mixl1) and trophectoderm (Cdx2, Eomes, and Elf5) markers (PubMed:28982712).|||Belongs to the grh/CP2 family. CP2 subfamily.|||Expressed at low levels in 10.5- and 11.5-dpc embryos. Expression was not detected at 12.5- and 13.5-dpc. Highly expressed in the epithelial monolayer lining in a subset of tubules of embryonic kidney cortex. Low levels of expression were detected in 16.5-dpc embryonic intestine, limb, lung, and skin. No expression was detected in the brain. Expression is regulated in at least two distinct sites, the pluripotent cells of the developing embryo and the epithelial cells lining the embryonic kidney distal convoluted tubules. Expressed in the ducts of submandibular and sublingual glands, isolated submandibular gland, parotid and lachrymal glands and nasal gland in 16 dpc embryos. At birth, the expression is detected in minor nasal glands in the olfactory epithelium, ducts of the mammary gland, male reproductive system, endolymphatic sac and lung. Expressed during renal development; first detected in the ureteric epithelium, at the distal end of the S-shaped body in nephron and subsequently in all nephric tubule, with expression localizing to more distal regions in the nephron during the maturation of the kidney.|||Forms homohexamers via its SAM-like domain (By similarity). Interacts with Mta1; which is indispensable for Tfcp2l1-mediated self-renewal-promoting effect and endoderm-inhibiting action (PubMed:28982712).|||Highly expressed in placenta, testis, small intestine, kidney and stomach (PubMed:11073954, PubMed:17079272). Low levels of expression in lung, mesenteric lymph nodes, muscle, ovary, and thymus (PubMed:11073954). No expression was detected in brain, heart, liver, and spleen (PubMed:11073954). Expressed in eccrine glands in the palm (PubMed:11073954). Expression is prominent in both kidney collecting ducts intercalated (IC) and principal (PC) cells (PubMed:28577314). Also expressed in the thick limb of Henle and connecting segments of the nephron (PubMed:28577314).|||Nucleus|||The Grh/CP2 DB domain is required for direct DNA-binding (By similarity). The Grh/CP2 DB domain is essential to maintain the undifferentiated state of embryonic stem cells (PubMed:28982712).|||The SAM-like domain is required for homohexamerization (By similarity).|||Transcription factor that facilitates establishment and maintenance of pluripotency in embryonic stem cells (ESCs) (PubMed:23942233, PubMed:26321140). With Klf2, acts as the major effector of self-renewal that mediates induction of pluripotency downstream of LIF/Stat3 and Wnt/beta-catenin signaling (PubMed:23942238, PubMed:23942233, PubMed:26321140). Required for normal duct development in the salivary gland and kidney (PubMed:17079272). Coordinates the development of the kidney collecting ducts intercalated (IC) and principal (PC) cells, which regulate acid-base and salt-water homeostasis, respectively (PubMed:28577314). Regulates the expression of IC genes including subunits B1 and D2 of the V-ATPase complex, Oxgr1, Ca12, Slc4a1, Aqp6 and IC-specific transcription factor Foxi1 (PubMed:28577314). Regulates also the expression of Jag1 and subsequent notch signaling in the collecting duct (PubMed:28577314). Jag1 initiates notch signaling in PCs but inhibits notch signaling in ICs (PubMed:28577314). Acts as a transcriptional suppressor that may suppress UBP1-mediated transcriptional activation (PubMed:11073954). Modulates the placental expression of CYP11A1 (By similarity). http://togogenome.org/gene/10090:Atad5 ^@ http://purl.uniprot.org/uniprot/Q4QY64 ^@ Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATR may stimulate the RAD9A dissociation.|||Belongs to the AAA ATPase family.|||Component of a heteropentameric replication factor ATAD5 RFC-like complex composed of one large subunit (ATAD5) and four small subunits (RFC2, RFC3, RFC4 and RFC5). Within the ATAD5 RFC-like complex, interacts with RFC2, RFC4 and RFC5. Within the ATAD5 RFC-like complex, interacts directly via-N terminal with RAD51; the interactions is enhanced under replication stress (By similarity). Interacts with RB1 predominantly in G1 phase via its LXCXE motif (PubMed:15983387). Interacts with RAD9A in growing cells (PubMed:15983387). The interaction with RAD9A is reduced after exposure to DNA replication-inhibiting agents (PubMed:15983387). Interacts with BRD4. Interacts with PCNA. Interacts with deubiquitinating enzyme USP1, and its associated factor, WDR48 (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Down-regulated by DNA replication-inhibiting agents.|||Expressed ubiquitously in all cell lines like teratocarcinoma, cell lymphoma, lymphoma.|||Has an important role in DNA replication and in maintaining genome integrity during replication stress. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway. As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle. This seems to be dependent on its ATPase activity. Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner. Ultimately this enables replication fork regression, breakage, and eventual fork restart. Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks. Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (By similarity).|||Nucleus http://togogenome.org/gene/10090:Plac8 ^@ http://purl.uniprot.org/uniprot/Q9JI48 ^@ Similarity ^@ Belongs to the cornifelin family. http://togogenome.org/gene/10090:Gja5 ^@ http://purl.uniprot.org/uniprot/A0A654ICB8|||http://purl.uniprot.org/uniprot/Q01231 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family. Alpha-type (group II) subfamily.|||Cell membrane|||Kidney, heart and skin, but most abundant in lung.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Gm21704 ^@ http://purl.uniprot.org/uniprot/O35698 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with splicing factor proteins SFRS3/SRP20, TRA2B/SFRS10, KHDRBS1/SAM68 and KHDRBS3.|||Nucleus|||Only expressed in spermatogonia and early spermatocytes, suggesting that expression is inactivated in the XY body during meiosis.|||Overexpression of Rbmy proteins in mice carrying the Y(d1) deletion that removes most of the multi-copy Rbmy gene cluster does not have any effect and fails to reduce the frequency of abnormal sperm. These results raize the question of the role of Rbmy proteins in sperm development.|||RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs.|||Testis-specific.|||The RBMY1 proteins are encoded by repeated regions of the Y chromosome. The exact number of functional copies is unclear and may vary between individuals, and some of them may represent pseudogenes. http://togogenome.org/gene/10090:Ccdc93 ^@ http://purl.uniprot.org/uniprot/E9QAD4|||http://purl.uniprot.org/uniprot/Q7TQK5|||http://purl.uniprot.org/uniprot/Q8BUE0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC93 family.|||Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes and is dependent on its interaction with WASHC2C.|||Early endosome|||Interacts with COMMD1, COMMD2 COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8, COMMD9, COMMD10, WASHC1. Interacts directly with WASHC2C. Interacts with CCDC93; proposed to be a component of the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22 and CCDC93; in the complex interacts directly with CCDC22. Interacts with VPS35L; associates with the retriever complex. Interacts with SNX17 and SNX31. http://togogenome.org/gene/10090:Olfm2 ^@ http://purl.uniprot.org/uniprot/Q8BM13 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||During embryonic eye development, first detected at 12 dpc with maximum levels at 19.5 dpc and down-regulation of expression postnatally. In brain, levels increase from 13.5 dpc to postnatal day 6 and decrease in the adult.|||Expressed in the brain (at protein level) (PubMed:22632720). In the developing eye, first detected at 12 dpc in the retinal pigmented epithelium and preferentially expressed in differentiating retinal ganglion cells between 15 and 18 dpc (PubMed:21228389). In the brain, expression is detected mainly in the olfactory bulb, cortex, piriform cortex, olfactory trabeculae, and inferior and superior colliculus (PubMed:25218043). In the adult eye, expression is detected mainly in retinal ganglion cells (PubMed:25218043). Expressed in carotid arteries (PubMed:28062493).|||Involved in transforming growth factor beta (TGF-beta)-induced smooth muscle differentiation (By similarity). TGF-beta induces expression and nuclear translocation of OLFM2 where it binds to SRF, causing its dissociation from the transcriptional repressor HEY2/HERP1 and facilitating binding of SRF to target genes (By similarity). Plays a role in AMPAR complex organization (PubMed:25218043). Is a regulator of vascular smooth-muscle cell (SMC) phenotypic switching, that acts by promoting RUNX2 and inhibiting MYOCD binding to SRF. SMC phenotypic switching is the process through which vascular SMCs undergo transition between a quiescent contractile phenotype and a proliferative synthetic phenotype in response to pathological stimuli. SMC phenotypic plasticity is essential for vascular development and remodeling (By similarity).|||Membrane|||No gross abnormalities with normal lifespan but mutants display reduced exploration, locomotion and olfactory sensitivity, reduced amplitude of the first negative wave in the visual evoked potential test, abnormal motor coordination, anxiety-related behavior and changes in AMPAR complex composition.|||Nucleus|||Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including OLFM2. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (PubMed:22632720). Interacts with GRIA2 (PubMed:25218043). Interacts with OLFM1 and OLFM3 (By similarity). Interacts with SRF; the interaction promotes dissociation of SRF from the transcriptional repressor HEY2 (By similarity). Interacts with RUNX2 (By similarity).|||Secreted|||Synapse http://togogenome.org/gene/10090:Spink12 ^@ http://purl.uniprot.org/uniprot/Q9D256 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in epydiymis, in the caput.|||Inhibits trypsin.|||Secreted http://togogenome.org/gene/10090:Aqp8 ^@ http://purl.uniprot.org/uniprot/A0A0X1KG59|||http://purl.uniprot.org/uniprot/P56404|||http://purl.uniprot.org/uniprot/Q3UJ16 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Basolateral cell membrane|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Channel that allows the facilitated permeation of water and uncharged molecules, such as hydrogen peroxide and the neutral form of ammonia (NH3), through cellular membranes such as plasma membrane, inner mitochondrial membrane and endoplasmic reticulum membrane of several tissues (PubMed:27256569, PubMed:9388476, PubMed:15647389, PubMed:15948717, PubMed:16624991, PubMed:21117174). The transport of ammonia neutral form induces a parallel transport of proton, at alkaline pH when the concentration of ammonia is high (By similarity). However, it is unclear whether the transport of proton takes place via the aquaporin or via an endogenous pathway (By similarity). Also, may transport ammonia analogs such as formamide and methylamine, a transport favourited at basic pH due to the increase of unprotonated (neutral) form, which is expected to favor diffusion (By similarity). In vitro, may be also permeable to urea but not to glycerol (PubMed:9388476). Does not transport urea or glycerol (By similarity). The water transport mechanism is mercury- and copper-sensitive and passive in response to osmotic driving forces (PubMed:9388476). At the canicular plasma membrane, mediates the osmotic transport of water toward the bile canaliculus and facilitates the cAMP-induced bile canalicular water secretion, a process involved in bile formation (By similarity). In addition, mediates the hydrogen peroxide release from hepatocyte mitochondria that modulates the SREBF2-mediated cholesterol synthesis and facilitates the mitochondrial ammonia uptake which is metabolized into urea, mainly under glucagon stimulation (By similarity). In B cells, transports the CYBB-generated hydrogen peroxide from the external leaflet of the plasma membrane to the cytosol to promote B cell activation and differentiation for signal amplification (PubMed:27256569). In the small intestine and colon system, mediates water transport through mitochondria and apical membrane of epithelial cells (By similarity). May play an important role in the adaptive response of proximal tubule cells to acidosis possibly facilitating mitochondrial ammonia transport (By similarity).|||Down-regulated by fasting.|||Expressed in placenta (PubMed:9388476). Highly expressed in the epithelial layer of gall-bladders (PubMed:15859952). Expressed in heart, kidney, submandibular gland, liver, small intestine, colon, testes, and epididymis (PubMed:15647389, PubMed:9388476). In testes, expressed in spermatogenic cells (PubMed:15647389).|||Homozygous mice for AQP8 have normal appearance, survival, and growth (PubMed:15647389). Homozygous mice female for AQP8 exhibit increased fertility and numbers of oocytes in ovulation (PubMed:21117174). Homozygous male mice show an unaffected fertility (PubMed:21117174). Homozygous pregnant mice have a significantly higher number of embryos and fetal/neonatal weight is also significantly greater (PubMed:21602842). Exhibit a greater amount of amniotic fluid and placental weight is significantly larger (PubMed:21602842).|||Membrane|||Mitochondrion inner membrane|||N-glycosylated.|||Persulfidation at Cys-53 is required to gate AQP8 channel; under stress condition, hydrogen peroxide accumulates in the cell leading to CBS activation that produces hydrogen sulfide inducing persulfidation of oxidized Cys-53 (C53-SOH).|||Reversibly gated by a two-step sulfenylation-persulfidation process in cells undergoing diverse stresses.|||Smooth endoplasmic reticulum membrane|||Strongly expressed between fetal day 17 and birth as well as at weaning and thereafter.|||Sulfenylation at Cys-53(C53-SOH) when hydrogen peroxide flows through the AQP8 channel, making it susceptible to hydrogen sulfide produced by CBS. http://togogenome.org/gene/10090:Limk1 ^@ http://purl.uniprot.org/uniprot/E9PVB6|||http://purl.uniprot.org/uniprot/P53668|||http://purl.uniprot.org/uniprot/Q3UR47 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated on Thr-508 by ROCK1 and PAK1, resulting in activation. Phosphorylated by PAK4 which increases the ability of LIMK1 to phosphorylate cofilin. Phosphorylated at Ser-323 by MAPKAPK2 during activation of VEGFA-induced signaling, which results in activation of LIMK1 and promotion of actin reorganization, cell migration, and tubule formation of endothelial cells. Dephosphorylated and inactivated by SSH1. Phosphorylated by CDC42BP (By similarity).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cytoplasm|||Expressed in ventral neural tube and axonal projections at 12.5 dpc-13 dpc (at protein level).|||Highest expression in the nervous system, particularly in the spinal cord and the cranial nerve and dorsal root ganglia.|||Nucleus|||Self-associates to form homodimers. Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization and subsequent transphosphorylation. Interacts with CDKN1C (By similarity). Interacts (via LIM domain) with the cytoplasmic domain of NRG1 (By similarity). Interacts with NISCH (PubMed:18332102). Interacts with SSH1 (PubMed:15660133). Interacts with RLIM and RNF6 (PubMed:16204183). Interacts (via LIM zinc-binding domains) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with CDC42BPA, CDC42BPB and FAM89B/LRAP25 (PubMed:25107909).|||Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics (PubMed:15056216, PubMed:16204183). Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:15056216). Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development (By similarity).|||Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF6 leads to proteasomal degradation through the 26S proteasome, modulating LIMK1 levels in the growth cone and its effect on axonal outgrowth. Also polyubiquitinated by RLIM.|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Rdh16f2 ^@ http://purl.uniprot.org/uniprot/Q8K3M0|||http://purl.uniprot.org/uniprot/Q8K3M1 ^@ Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. http://togogenome.org/gene/10090:Tipin ^@ http://purl.uniprot.org/uniprot/Q91WA1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CSM3 family.|||Cytoplasm|||Expressed in brain.|||Expression peaks between 11 dpc and 15 dpc. At 7.5 dpc, expressed in germ cell layers. At 14.5 dpc, expressed at highest levels in thymus, liver, gastrointestinal tract, lung and the rapidly proliferating ventricular zone of the brain.|||Interacts with MCM6 and MCM7 (By similarity). Interacts with TIMELESS (via N-terminus), which impairs TIMELESS self-association. Interacts with RPA2 and PRDX2.|||Nucleus|||Plays an important role in the control of DNA replication and the maintenance of replication fork stability. Important for cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. Forms a complex with TIMELESS and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. http://togogenome.org/gene/10090:Oga ^@ http://purl.uniprot.org/uniprot/Q9EQQ9 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 84 family.|||Cleaves GlcNAc but not GalNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrates but not p-nitrophenyl-beta-GalNAc or p-nitrophenyl-alpha-GlcNAc (in vitro) (PubMed:16517082). Does not bind acetyl-CoA and does not have histone acetyltransferase activity.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Expressed throughout development from blastocyst stage to embryonic day 16.5.|||Expression in the liver oscillates in a circadian manner with peak levels at CT8-CT12.|||Monomer (By similarity). Interacts with CLOCK.|||Nucleus|||Proteolytically cleaved by caspase-3 during apoptosis. The fragments interact with each other; cleavage does not decrease enzyme activity.|||Was initially identified as a bi-functional protein that has an N-terminal domain with O-GlcNAcase activity and a C-terminal domain with histone acetyltransferase activity (PubMed:16356930). The histone acetyltransferase activity was detected only when the protein was expressed in mammalian cells, but not when expressed in bacterial cells, suggesting that the histone acetyltransferase activity might be due to the presence of a contaminant. Characterization of the human protein shows that this protein does not bind acetyl-CoA and therefore cannot have acetyltransferase activity. http://togogenome.org/gene/10090:Rhox2h ^@ http://purl.uniprot.org/uniprot/K7N6P1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Klhdc2 ^@ http://purl.uniprot.org/uniprot/Q4G5Y1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter KLHDC2. Interacts with CREB3; interaction is direct and specific as it does not interact with CREB1, ATF4, ATF6, JUN, FOS, CEBPA or herpes simplex virus transactivator VP16.|||Nucleus|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC2) complex specifically recognizes proteins with a diglycine (Gly-Gly) at the C-terminus, leading to their ubiquitination and degradation. The CRL2(KLHDC2) complex mediates ubiquitination and degradation of truncated SELENOK and SELENOS selenoproteins produced by failed UGA/Sec decoding, which end with a diglycine. The CRL2(KLHDC2) complex also recognizes proteolytically cleaved proteins ending with Gly-Gly, such as the N-terminal fragment of USP1, leading to their degradation. May also act as an indirect repressor of CREB3-mediated transcription by interfering with CREB3-DNA-binding. http://togogenome.org/gene/10090:Tmem269 ^@ http://purl.uniprot.org/uniprot/Q9D4Y8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Abcb9 ^@ http://purl.uniprot.org/uniprot/Q9JJ59 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent low-affinity peptide transporter which translocates a broad spectrum of peptides from the cytosol to the lysosomal lumen for degradation. Displays a broad peptide length specificity from 6-mer up to at least 59-mer peptides with an optimum of 23-mers. Binds and transports smaller and larger peptides with the same affinity. Favors positively charged, aromatic or hydrophobic residues in the N- and C-terminal positions whereas negatively charged residues as well as asparagine and methionine are not favored.|||Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.|||Divided into an N-terminal domain (TMD0) comprising four transmembrane helices and the following core domain (coreABCB9). TMD0 is required for lysosomal localization and LAMP1, LAMP2 and YIF1B interaction. The core domain is required for homodimerization and peptide transport activity.|||Highly expressed in testis, particularly in the Sertoli cells of the seminiferous tubules, and at moderate levels in brain and spinal cord.|||Homodimer. Interacts (via TMD0 region) with LAMP1; this interaction strongly stabilizes ABCB9 and protects ABCB9 against lysosomal degradation. Interacts (via TMD0 region) with LAMP2 (isoform LAMP-2B). Interacts (via TMD0) with YIF1B; this interaction allows (but is not essential) the ER-to-Golgi trafficking and strongly depends on a salt bridge within TMD0.|||Lysosome membrane http://togogenome.org/gene/10090:Zfp654 ^@ http://purl.uniprot.org/uniprot/Q9DAU9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Scn1b ^@ http://purl.uniprot.org/uniprot/P97952 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel auxiliary subunit SCN1B (TC 8.A.17) family.|||Cell membrane|||Cell projection|||Component of a voltage-sensitive sodium channel complex that consists of a pore-forming alpha subunit and one or more regulatory beta subunits. Interacts with SCN4A. Interacts with NFASC. Interacts with SCN10A (By similarity). Interacts with SCN1A. Interacts with SCN3A. Interacts with SCN5A. Interacts with SCN8A (By similarity).|||Detected in hippocampus CA3 bipolar neurons (at protein level) (PubMed:19710327). Detected in skeletal muscle (PubMed:9013777).|||Perikaryon|||Regulatory subunit of multiple voltage-gated sodium channel complexes that play important roles in excitable membranes in brain, heart and skeletal muscle. Enhances the presence of the pore-forming alpha subunit at the cell surface and modulates channel gating characteristics and the rate of channel inactivation. Modulates the activity of a variety of pore-forming alpha subunits, such as SCN1A, SCN2A, SCN3A, SCN4A, SCN5A and SCN10A.|||axon http://togogenome.org/gene/10090:Ube2ql1 ^@ http://purl.uniprot.org/uniprot/A0PJN4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Interacts with FBXW7.|||Nucleus|||Probable E2 ubiquitin-protein ligase that catalyzes the covalent attachment of ubiquitin to target proteins. May facilitate the monoubiquitination and degradation of MTOR and CCNE1 through interaction with FBXW7. http://togogenome.org/gene/10090:Ppp2r1a ^@ http://purl.uniprot.org/uniprot/Q76MZ3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphatase 2A regulatory subunit A family.|||Cytoplasm|||Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.|||Lateral cell membrane|||Nucleus|||PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites (PubMed:22417654). Interacts with IPO9 (By similarity). Interacts with TP53 and SGO1 (By similarity). Interacts with PLA2G16; this interaction might decrease PP2A activity (By similarity). Interacts with CTTNBP2NL (By similarity). Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (By similarity).Interacts with CIP2A; this interaction stabilizes CIP2A (By similarity). Interacts with PABIR1/FAM122A (By similarity). Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin (PubMed:16258073). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2 (By similarity).|||The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit (PubMed:10100624, PubMed:26974206). Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT (By similarity). Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis (By similarity). Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (PubMed:26974206, PubMed:33505023). Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (PubMed:33505023).|||centromere|||dendrite http://togogenome.org/gene/10090:Ccni ^@ http://purl.uniprot.org/uniprot/Q8C7E2|||http://purl.uniprot.org/uniprot/Q9Z2V9 ^@ Similarity ^@ Belongs to the cyclin family. http://togogenome.org/gene/10090:Pxn ^@ http://purl.uniprot.org/uniprot/F8VQ28|||http://purl.uniprot.org/uniprot/Q8VI36 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the paxillin family.|||Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion.|||Interacts in vitro with VCL/vinculin as well as to the SH3 domain of SRC and, when tyrosine phosphorylated, to the SH2 domain of CRK (By similarity). Interacts with GIT1 (By similarity). Interacts with NUDT16L1/SDOS (PubMed:11805099). Interacts with PTK2/FAK1 (PubMed:11799401). Interacts with PTK2B/PYK2 (PubMed:8940124). Interacts with ASAP2 (By similarity). Interacts with unphosphorylated ITGA4 (By similarity). Interacts with RNF5 (By similarity). Interacts with PDCD10 (By similarity). Interacts with NEK3, the interaction is prolactin-dependent (By similarity). Interacts with PTK6 (By similarity). Interacts with TGFB1I1 (By similarity). Interacts with SORBS1 (By similarity). Interacts with PARVB (By similarity). Interacts (via LD motif 4) with PARVA/PARVIN (PubMed:11134073). Interacts (via LD motif 4) with ILK (By similarity). Interacts (via cytoplasmic domain) with CEACAM1; the interaction is phosphotyrosyl-dependent (By similarity). Interacts with LIMA1; this complex stabilizes actin dynamics (By similarity). Interacts with CD36 (via C-terminus) (By similarity). Interacts with TRIM15 (By similarity).|||Phosphorylated by MAPK1/ERK2. Phosphorylated on tyrosine residues during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens. Phosphorylation at Ser-244 by CDK5 reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation (By similarity). Phosphorylation at Tyr-31 and Tyr-118 by PTK6 promote the activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion (By similarity). Phosphorylation at Ser-250 by SLK is required for PXN redistribution and cell motility (By similarity).|||cell cortex|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Phyhd1 ^@ http://purl.uniprot.org/uniprot/Q9DB26 ^@ Function|||Similarity ^@ 2-oxoglutarate(2OG)-dependent dioxygenase that catalyzes the conversion of 2-oxoglutarate to succinate and CO(2) in an iron-dependent manner. However, does not couple 2OG turnover to the hydroxylation of acyl-coenzyme A derivatives, implying that it is not directly involved in phytanoyl coenzyme-A metabolism. Does not show detectable activity towards fatty acid CoA thioesters.|||Belongs to the PhyH family. PHYHD1 subfamily. http://togogenome.org/gene/10090:Vmn2r30 ^@ http://purl.uniprot.org/uniprot/K7N5W1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:AI597479 ^@ http://purl.uniprot.org/uniprot/Q922M7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ashwin family.|||Component of the tRNA-splicing ligase complex.|||Nucleus http://togogenome.org/gene/10090:Dpm2 ^@ http://purl.uniprot.org/uniprot/Q545R7|||http://purl.uniprot.org/uniprot/Q9Z324 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DPM2 family.|||Component of the dolichol-phosphate mannose (DPM) synthase complex composed of DPM1, DPM2 and DPM3; in the complex interacts directly with DPM3. Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts with PIGA, PIGC and PIGQ.|||Component of the dolichol-phosphate mannose (DPM) synthase complex.|||Endoplasmic reticulum membrane|||Membrane|||Regulates the biosynthesis of dolichol phosphate-mannose. Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization and stable expression of DPM1. Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. May act by regulating the GPI-GNT complex.|||Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization. http://togogenome.org/gene/10090:Sertad1 ^@ http://purl.uniprot.org/uniprot/Q9JL10 ^@ Developmental Stage|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. Stimulates E2F1/TFDP1 transcriptional activity. Renders the activity of cyclin D1/CDK4 resistant to the inhibitory effects of CDKN2A/p16INK4A.|||Detected as early as 7 dpc and persist until, at least, 17 dpc.|||Detected at in testis, lung and, at lower levels, in muscle, liver, spleen, brain and heart.|||Interacts with the PHD-bromodomain of TIF1, TRIM28/TIF1B and p300/CBP. Interacts with E2F1 and TFDP1; modulates transactivation activity of TFDP1/E2F complexes. Also interacts with CDK4.|||Polyubiquitinated, which promotes proteasomal degradation. http://togogenome.org/gene/10090:Lrig1 ^@ http://purl.uniprot.org/uniprot/P70193 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation.|||Cell membrane|||Contains LRR and Ig-domains that can mediate low-affinity interaction with EGFR. The LRRs and the Ig-domains are each sufficient for EGFR/ERBB1 binding. This interaction is abolished only when both the LRRs and the Ig-domains are deleted.|||Detected in brain (at protein level) (PubMed:12067728). Predominantly expressed in the brain, restricted to a small subset of glial cells, such as Bergmann glial cells of the cerebellum and glial cells in the nerve fiber layer of the olfactory bulb. Expressed also in the skin. Low expression is detected in the thymus and heart. No expression in the kidney, liver, lung or small intestine.|||Interacts (via extracellular LRR and Ig-like domains) with EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 (via extracellular domain). The physiological relevance of the interaction is controversial; LRIG1 may have low affinity for EGFR, and interaction may occur only when high levels of both proteins are present.|||Mutant mice are born at the expected Mendelian rate and initially display no visible phenotype. One to four months after birth, they develop skin abnormalities including alopecia and epidermal hyperplasia that are reminiscent of psoriasis. http://togogenome.org/gene/10090:Vmn1r255 ^@ http://purl.uniprot.org/uniprot/K9J7G9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gapdhs ^@ http://purl.uniprot.org/uniprot/A0A0R4J0X7|||http://purl.uniprot.org/uniprot/Q64467|||http://purl.uniprot.org/uniprot/S4R2G5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.|||Cytoplasm|||First expressed at day 20 in post-meiotic germ cells. Levels increase until day 24 and then remain constant during maturity.|||Homotetramer.|||May play an important role in regulating the switch between different pathways for energy production during spermiogenesis and in the spermatozoon. Required for sperm motility and male fertility.|||Mice display greatly reduced ATP levels in sperm, severely impaired sperm motility and are infertile.|||Testis specific.|||The testis-specific N-terminal extension mediates tight association with the cytoskeletal fibrous sheath of the spermatozoa flagellum, possibly via interchain disulfide-bonding of Cys-33 with sheath components. http://togogenome.org/gene/10090:Clca4b ^@ http://purl.uniprot.org/uniprot/Q3UW98 ^@ Similarity ^@ Belongs to the CLCR family. http://togogenome.org/gene/10090:Hnf4a ^@ http://purl.uniprot.org/uniprot/B9VVT5|||http://purl.uniprot.org/uniprot/B9VVT6|||http://purl.uniprot.org/uniprot/P49698 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-458 lowers transcriptional activation by about two-fold.|||Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Binds fatty acids.|||Expressed in the liver, pancreas and colon in a circadian manner.|||Homodimerization is required for HNF4-alpha to bind to its recognition site (By similarity). Interacts with CLOCK, BMAL1 and PER1 (By similarity). Interacts with PER2 (PubMed:20159955). Interacts with CRY1 and CRY2 (PubMed:28751364). Interacts with NR0B2/SHP; the resulting heterodimer is transcriptionnally inactive (By similarity). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2 that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (By similarity).|||Nucleus|||Pancreatic beta-cells-specific knockout results in hyperinsulinemia and hypoglycemia.|||Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK reduces the ability to form homodimers and bind DNA (By similarity).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitatating the recruitment of RNA pol II to the promoters of target genes (By similarity). Activates the transcription of CYP2C38 (PubMed:30555544). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698). http://togogenome.org/gene/10090:Afmid ^@ http://purl.uniprot.org/uniprot/Q8K4H1 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the kynurenine formamidase family.|||Catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. Kynurenine may be further oxidized to nicotinic acid, NAD(H) and NADP(H). Required for elimination of toxic metabolites.|||Down-regulated upon IL2-mediated activation. Transcriptional activation correlates with reduced histone acetylation.|||Highly expressed in liver. Expressed in kidney. Weakly or not expressed in other tissues.|||Homodimer.|||Mice display sclerosis of kidney glomeruli, possibly due to failures in the elimination of toxic metabolites.|||Nucleus|||The Afmid gene shares a bidirectional promoter region with Tk1 gene.|||The N-terminus is blocked.|||The main chain amide nitrogen atoms of the second glycine and its adjacent residue in the HGGXW motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage.|||cytosol http://togogenome.org/gene/10090:Or5an1 ^@ http://purl.uniprot.org/uniprot/Q7TQR9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Litaf ^@ http://purl.uniprot.org/uniprot/Q9JLJ0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDIP1/LITAF family.|||Cell membrane|||Cytoplasm|||Detected in brain, heart, lung, liver, spleen and bone marrow (PubMed:22160695). Detected in myelinating Schwann cells in sciatic nerve and in bone marrow-derived macrophages (at protein level) (PubMed:22729949). Widely expressed. Highly expressed in liver.|||Early endosome membrane|||Endosome membrane|||Expression in sciatic nerve is low in neonates, culminates seven days after birth and decreases rapidly thereafter (at protein level) (PubMed:22729949). Strong expression is detected at E.7 and drops at 11 dpc.|||Golgi apparatus membrane|||Late endosome membrane|||Lysosome membrane|||Monomer. Interacts with NEDD4 (PubMed:11042109). Interacts (via PSAP motif) with TSG101, a component of the ESCRT-I complex (endosomal sorting complex required for transport I). Interacts with WWOX. Interacts with STAM, a component of the ESCRT-0 complex; the interaction is direct. Identified in a complex with STAM and HGS; within this complex, interacts directly with STAM, but not with HGS. Interacts with STAT6 (PubMed:15793005).|||No visible phenotype. Mice are born at the expected Mendelian rate and are fertile. Mutant mice display altered responses to nerve crush injury, with higher numbers of macrophages in injured nerves five days after nerve crush injury, but at later time points macrophage numbers in injured nerves are normal. Bone marrow-derived macrophages from mutant mice display increased migration in response to CCL3, but not in the absence of CCL3 (PubMed:22729949). Mutant mice show dramatically increased survival in response to a dose of lipopolysaccharide (LPS) that causes rapid death of 40% of wild-type mice (PubMed:22160695).|||Nucleus|||Phosphorylated on tyrosine residues in response to EGF.|||Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation. Plays a role in targeting endocytosed EGFR and ERGG3 for lysosomal degradation, and thereby helps down-regulate downstream signaling cascades (PubMed:23166352). Helps recruit the ESCRT complex components TSG101, HGS and STAM to cytoplasmic membranes. Probably plays a role in regulating protein degradation via its interaction with NEDD4 (By similarity). May also contribute to the regulation of gene expression in the nucleus. Binds DNA (in vitro) and may play a synergistic role with STAT6 in the nucleus in regulating the expression of various cytokines (PubMed:15793005, PubMed:21980379). May regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10 (PubMed:12355436, PubMed:15025820, PubMed:16954198, PubMed:21980379, PubMed:22160695).|||The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes. It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate.|||The PPxY motif mediates interaction with WWOX and NEDD4.|||Up-regulated in macrophages exposed to lipopolysaccharide (LPS) (at protein level) (PubMed:15793005). By estrogen and lipopolysaccharides (LPS). http://togogenome.org/gene/10090:Icam5 ^@ http://purl.uniprot.org/uniprot/Q60625 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. ICAM family.|||Expressed on neurons in the most rostral segment of the mammalian brain, the telencephalon.|||Glycosylation at Asn-54 is critical for functional folding.|||ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2).|||Membrane http://togogenome.org/gene/10090:Omg ^@ http://purl.uniprot.org/uniprot/Q63912 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to RTN4R.|||Cell adhesion molecule contributing to the interactive process required for myelination in the central nervous system.|||Cell membrane|||Do not confuse oligodendrocyte-myelin glycoprotein (OMG) with myelin-oligodendrocyte glycoprotein (MOG).|||O-glycosylated in its Ser/Thr-rich repeat domain.|||Oligodendrocytes and myelin of the central nervous system. http://togogenome.org/gene/10090:Bmi1 ^@ http://purl.uniprot.org/uniprot/P25916 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a PRC1-like complex (PubMed:16359901). Identified in a PRC1-like HPRC-H complex with CBX2, CBX4, CBX8, PHC1, PHC2, PHC3, RING1 and RNF2 (By similarity). Interacts with RNF2/RING2 (PubMed:16359901, PubMed:16710298). Interacts with RING1 (PubMed:16359901, PubMed:16710298). Part of a complex that contains RNF2, UB2D3 and BMI1, where RNF2 and BMI1 form a tight heterodimer, and UB2D3 interacts only with RNF2. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A. Interacts with CBX7 and CBX8 (PubMed:16359901). Interacts with SPOP. Part of a complex consisting of BMI1, CUL3 and SPOP. Interacts with E4F1 (By similarity). Interacts with PHC2 (PubMed:16359901). Interacts with zinc finger protein ZNF277 (PubMed:20808772). May be part of a complex including at least ZNF277, BMI1 and RNF2/RING2 (PubMed:20808772).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. The complex composed of RNF2, UB2D3 and BMI1 binds nucleosomes, and has activity only with nucleosomal histone H2A. In the PRC1-like complex, regulates the E3 ubiquitin-protein ligase activity of RNF2/RING2 (By similarity).|||Cytoplasm|||Detected in most organs with high expression levels in thymus, heart, brain and testis.|||Down-regulated by oxidative stress.|||May be polyubiquitinated; which does not lead to proteasomal degradation (By similarity). Monoubiquitinated.|||Nucleus http://togogenome.org/gene/10090:Adprhl1 ^@ http://purl.uniprot.org/uniprot/Q8BGK2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although it belongs to the ADP-ribosylglycohydrolase family, lacks the metal-binding and substrate-binding residues, suggesting that it has no hydrolase activity.|||Belongs to the ADP-ribosylglycohydrolase family.|||Expressed in the embryonic heart at E11.5.|||Required for myofibril assembly and outgrowth of the cardiac chambers in the developing heart (By similarity). Appears to be catalytically inactive, showing no activity against O-acetyl-ADP-ribose (PubMed:17075046).|||sarcomere http://togogenome.org/gene/10090:Ces3b ^@ http://purl.uniprot.org/uniprot/Q8VCU1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Endoplasmic reticulum lumen|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. http://togogenome.org/gene/10090:Nadk ^@ http://purl.uniprot.org/uniprot/P58058|||http://purl.uniprot.org/uniprot/Q3UGI1 ^@ Similarity ^@ Belongs to the NAD kinase family. http://togogenome.org/gene/10090:Pacsin2 ^@ http://purl.uniprot.org/uniprot/Q3TDA7|||http://purl.uniprot.org/uniprot/Q9WVE8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PACSIN family.|||Cell membrane|||Cell projection|||Cytoplasm|||Cytoplasmic vesicle membrane|||Early endosome|||Endosome membrane|||Homodimer (PubMed:20471395). May form heterooligomers with other PACSINs (PubMed:11082044). Interacts (via NPF motifs) with EHD1 (via EH domain) (PubMed:15930129). Interacts (via NPF motifs) with EHD2 (via EH domain); this interaction probably stabilizes the caveolae (By similarity). Interacts with EHD3 (PubMed:15930129). Interacts (via the SH3 domain) with MICALL1 (By similarity). Interacts with RAC1 (PubMed:21693584). Interacts (via SH3 domain) with DNM1, SYN1, SYNJ1 and WASL (PubMed:11082044). Interacts (via F-BAR domain) with CAV1; this interaction induces membrane tubulation (PubMed:21610094). Interacts with TRPV4 (PubMed:16627472).|||Membrane|||Phosphorylated by casein kinase 2 (CK2). Phosphorylation by PKC probably decreases the membrane binding and tubulation capacities of PACSIN2, thereby modulating the lifetime of caveolae (PubMed:26092940).|||Recycling endosome membrane|||Regulates the morphogenesis and endocytosis of caveolae (PubMed:21807942). Lipid-binding protein that is able to promote the tubulation of the phosphatidic acid-containing membranes it preferentially binds. Plays a role in intracellular vesicle-mediated transport. Involved in the endocytosis of cell-surface receptors like the EGF receptor, contributing to its internalization in the absence of EGF stimulus.|||Results in loss of morphologically defined caveolae.|||The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation (PubMed:20188097, PubMed:20471395). Autoinhibition of these functions is mediated by an interaction between the SH3 and F-BAR domains (By similarity). The F-Bar domain also mediates the binding to the cell actin cytoskeleton through the interaction with CAV-1 (PubMed:21610094).|||Widely expressed (at protein level).|||caveola|||cytoskeleton|||ruffle membrane http://togogenome.org/gene/10090:Tsn ^@ http://purl.uniprot.org/uniprot/Q545E6|||http://purl.uniprot.org/uniprot/Q62348 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the translin family.|||Cytoplasm|||DNA-binding protein that specifically recognizes consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. Seems to recognize single-stranded DNA ends generated by staggered breaks occurring at recombination hot spots.|||Exhibits both single-stranded and double-stranded endoribonuclease activity. May act as an activator of RNA-induced silencing complex (RISC) by facilitating endonucleolytic cleavage of the siRNA passenger strand.|||Nucleus|||Ring-shaped heterooctamer of six TSN and two TSNAX subunits, DNA/RNA binding occurs inside the ring. http://togogenome.org/gene/10090:Gm715 ^@ http://purl.uniprot.org/uniprot/A0A804C8T0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAPSTR1 family.|||Homooligomer. Heterooligomer with HAPSTR1; the interaction is direct and stabilizes HAPSTR1 independently of HUWE1. Interacts with HUWE1.|||Nucleus|||Together with HAPSTR1 plays a central regulatory role in the cellular response to molecular stressors, such as DNA damage, nutrient scarcity, and protein misfolding. Regulates these multiple stress response signaling pathways by stabilizing HAPSTR1, but also independently of HAPSTR1. http://togogenome.org/gene/10090:Or8d2 ^@ http://purl.uniprot.org/uniprot/Q7TRB8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm20873 ^@ http://purl.uniprot.org/uniprot/J3QMQ9 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Slc10a7 ^@ http://purl.uniprot.org/uniprot/Q5PT53 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Cell membrane|||Embryos at gestational age 12.5 dpc show the weakest SLC10A7 expression, mainly in the heart trabeculae of the developing heart and the cartilage of the vertebrae. From 14.5 dpc onwards, expression becomes more ubiquitous, with the strongest level observed at 16.5 dpc and postnatal day P0. At 14.5 dpc, it is strongly expressed in cartilaginous structures in the mandible, in the epithelial compartment of cap stage teeth, in the digits, in the spine and in the lung. At 16.5 dpc, transcripts are mostly localized in the inner dental epithelium and in the epithelial loop of bell stage teeth. At 18.5 dpc expression is observed in the inner dental epithelium of incisors, and in ameloblasts and odontoblasts of molars. At postnatal day P0 there is strong expression in the papillary layer of the oral mucous membrane underneath the palate, as well as in the ameloblast layer of emerging teeth. At postnatal day P10, it is localized to the growth plate of several long bones, such as the forefoot digits, the hindfoot tarsals and the humerus, and expression is more intense in the chondrocytes of the hypertrophic zone.|||Endoplasmic reticulum membrane|||Expressed in heart, brain, colon, lung, liver, adrenal gland, stomach and ovary. Also expressed weakly in small intestine. Expressed in skeletal tissues (PubMed:30082715).|||Golgi apparatus membrane|||Involved in teeth and skeletal development. Has an essential role in the biosynthesis and trafficking of glycosaminoglycans and glycoproteins to produce a proper functioning extracellular matrix. Required for extracellular matrix mineralization (PubMed:30082715). Also involved in the regulation of cellular calcium homeostasis (By similarity). Does not show transport activity towards bile acids or steroid sulfates (including taurocholate, cholate, chenodeoxycholate, estrone-3-sulfate, dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate).|||Knockout mice present with skeletal dysplasia including growth retardation at birth and at 8 weeks, alteration of long-bone morphology, craniofacial anomalies and advanced tarsal maturation at birth, associated with enamel defects. The proportion of heparan sulfate (HS) in cartilage of knockout mice is significantly reduced compared with wild-type animals. SLC10A7 deficiency has no impact on skeletal muscle heparan sulfate levels. http://togogenome.org/gene/10090:Grk2 ^@ http://purl.uniprot.org/uniprot/Q3U1V3|||http://purl.uniprot.org/uniprot/Q7TS64|||http://purl.uniprot.org/uniprot/Q99MK8 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.|||Cell membrane|||Cytoplasm|||In contrast to other AGC family kinases, the catalytic activity is solely regulated by the binding of substrates and ligands, not by phosphorylation of the kinase domain.|||Interacts with the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts with GIT1 (By similarity). Interacts with, and phosphorylates chemokine-stimulated CCR5 (By similarity). Interacts with ARRB1 (By similarity). Interacts with LPAR1 and LPAR2. Interacts with RALA in response to LPAR1 activation (By similarity). ADRBK1 and RALA mutually inhibit each other's binding to LPAR1 (By similarity). Interacts with ADRB2 (By similarity).|||Postsynapse|||Presynapse|||Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them (By similarity). Key regulator of LPAR1 signaling (By similarity). Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor (By similarity). Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (By similarity). Positively regulates ciliary smoothened (SMO)-dependent Hedgehog (Hh) signaling pathway by facilitating the trafficking of SMO into the cilium and the stimulation of SMO activity (By similarity). Inhibits relaxation of airway smooth muscle in response to blue light (PubMed:30284927).|||The PH domain binds anionic phospholipids and helps recruiting ADRBK1 from the cytoplasm to plasma membrane close to activated receptors. It mediates binding to G protein beta and gamma subunits, competing with G-alpha subunits and other G-betagamma effectors. http://togogenome.org/gene/10090:Trim67 ^@ http://purl.uniprot.org/uniprot/Q505D9 ^@ Subcellular Location Annotation ^@ Cytoplasm|||cytoskeleton http://togogenome.org/gene/10090:Tmprss5 ^@ http://purl.uniprot.org/uniprot/A2RSL0|||http://purl.uniprot.org/uniprot/Q9ER04 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play a role in hearing. http://togogenome.org/gene/10090:Nit2 ^@ http://purl.uniprot.org/uniprot/Q9JHW2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.|||Cytoplasm|||Has omega-amidase activity (PubMed:19596042, PubMed:28373563). The role of omega-amidase is to remove potentially toxic intermediates by converting 2-oxoglutaramate and 2-oxosuccinamate to biologically useful 2-oxoglutarate and oxaloacetate, respectively (PubMed:19596042). Can also hydrolyze gamma-monomethyl-alpha-ketoglutarate in vitro (PubMed:19596042).|||Homodimer. http://togogenome.org/gene/10090:Tns1 ^@ http://purl.uniprot.org/uniprot/A0A087WQS0|||http://purl.uniprot.org/uniprot/E9Q0S6|||http://purl.uniprot.org/uniprot/Q7TSV1|||http://purl.uniprot.org/uniprot/Q9DBT6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PTEN phosphatase protein family.|||Binds to actin filaments and interacts with phosphotyrosine-containing proteins. Interacts with STARD8. Interacts with protein phosphatase PPP1CA. Interacts (via N-terminus) with Rho GTPase-activating protein DLC1; the interaction is decreased by phosphorylation of TNS1. Interacts with tyrosine-phosphorylated proteins BCAR1/p130Cas and PTK2/FAK; the interactions are increased by phosphorylation of TNS1.|||Cell surface|||Extensively phosphorylated on serine and threonine residues in a p38 MAPK-dependent manner which reduces interaction with DLC1 and increases interaction with tyrosine-phosphorylated proteins including BCAR1/p130cas and PTK2/FAK. The majority of the phosphorylated Ser/Thr residues are immediately adjacent to a proline residue. Also phosphorylated on tyrosine residues.|||May act as a protein phosphatase and/or a lipid phosphatase (By similarity). Involved in fibrillar adhesion formation (By similarity). Essential for myofibroblast differentiation and myofibroblast-mediated extracellular matrix deposition (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in cell polarization and migration (By similarity). May be involved in cartilage development and in linking signal transduction pathways to the cytoskeleton (By similarity).|||Rapidly cleaved by calpain II.|||Reduced RHOA activity, reduced endothelial cell proliferation and migration, reduced endothelial cell tube formation and reduced angiogenesis.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Col4a5 ^@ http://purl.uniprot.org/uniprot/Q63ZW6 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.|||basement membrane http://togogenome.org/gene/10090:Itgb1bp1 ^@ http://purl.uniprot.org/uniprot/O35671 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in the brain.|||First expressed in the heart primordium at 8.5 dpc.|||Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminal region) with ITGB1 (via C-terminal cytoplasmic tail); the interaction prevents talin TLN1 binding to ITGB1 and KRIT1 and ITGB1 compete for the same binding site. Interacts with KRIT1 (via N-terminal NPXY motif); the interaction induces the opening conformation of KRIT1 and KRIT1 and ITGB1 compete for the same binding site. Isoform 2 does not interact with ITGB1. Interacts with CDC42 (GTP- or GDP-bound form); the interaction is increased with the CDC42-membrane bound forms and prevents both CDC42 activation and cell spreading. Interacts (via C-terminal domain region) with NME2. Interacts with FERMT2 and RAC1 (By similarity). Interacts (via N-terminus and PTB domain) with ROCK1.|||Key regulator of the integrin-mediated cell-matrix interaction signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. Plays a role in cell proliferation, differentiation, spreading, adhesion and migration in the context of mineralization and bone development and angiogenesis. Stimulates cellular proliferation in a fibronectin-dependent manner. Involved in the regulation of beta-1 integrin-containing focal adhesion (FA) site dynamics by controlling its assembly rate during cell adhesion; inhibits beta-1 integrin clustering within FA by directly competing with talin TLN1, and hence stimulates osteoblast spreading and migration in a fibronectin- and/or collagen-dependent manner. Acts as a guanine nucleotide dissociation inhibitor (GDI) by regulating Rho family GTPases during integrin-mediated cell matrix adhesion; reduces the level of active GTP-bound form of both CDC42 and RAC1 GTPases upon cell adhesion to fibronectin. Stimulates the release of active CDC42 from the membranes to maintain it in an inactive cytoplasmic pool. Participates in the translocation of the Rho-associated protein kinase ROCK1 to membrane ruffles at cell leading edges of the cell membrane, leading to an increase of myoblast cell migration on laminin. Plays a role in bone mineralization at a late stage of osteoblast differentiation; modulates the dynamic formation of focal adhesions into fibrillar adhesions, which are adhesive structures responsible for fibronectin deposition and fibrillogenesis. Plays a role in blood vessel development; acts as a negative regulator of angiogenesis by attenuating endothelial cell proliferation and migration, lumen formation and sprouting angiogenesis by promoting AKT phosphorylation and inhibiting ERK1/2 phosphorylation through activation of the Notch signaling pathway. Promotes transcriptional activity of the MYC promoter.|||Mice show severe defects in osteoblast mesenchymal cells to compaction, proliferation, differentiation, and mineralization and to a delay in bone nodule formation. Suffer also from an excessive microvessel growth.|||Nucleus|||Phosphorylation at Thr-38 seems to enhance integrin alpha5beta1-mediated cell adhesion. The degree of phosphorylation is regulated by integrin-dependent cell-matrix interaction (By similarity).|||cytoskeleton|||lamellipodium|||ruffle http://togogenome.org/gene/10090:H2bc1 ^@ http://purl.uniprot.org/uniprot/P70696 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates at 10 day postpartum (dpp), when pre-leptotene/leptotene spermatocytes first appear and when H2B expression shows a drastic decrease. Replaces H2B by 18 dpp in spermatocytes. Also present in metaphase oocytes and in the female pronucleus at fertilization and is also rapidly incorporated into the male pronucleus.|||Acetylated during spermatogenesis. Acetylated form is most abundant in spermatogonia compared to spermatocytes and round spermatids (By similarity).|||Belongs to the histone H2B family.|||Chromosome|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Mainly expressed in testis, and the corresponding protein is also present in mature sperm. Also present in metaphase oocytes (at protein level).|||Methylated at Lys-118 in spermatogonia, spermatocytes and round spermatids.|||Monoubiquitination at Lys-36 by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination of Lys-122 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated at Thr-117 in spermatogonia, spermatocytes and round spermatids.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers (PubMed:23884607). Interacts with H2AB1; preferentially dimerizes with H2AB1 to form nucleosomes (PubMed:28366643).|||Variant histone specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells (PubMed:23884607, PubMed:28366643). Entirely replaces classical histone H2B prior nucleosome to protamine transition and probably acts as a nucleosome dissociating factor that creates a more dynamic chromatin, facilitating the large-scale exchange of histones (PubMed:23884607). In condensing spermatids, the heterodimer between H2AB1 and H2BC1/TH2B is loaded onto the nucleosomes and promotes loading of transition proteins (TNP1 and TNP2) onto the nucleosomes (PubMed:28366643). Inclusion of the H2AB1-H2BC1/TH2B dimer into chromatin opens the nucleosomes, releasing the nucleosomal DNA ends and allowing the invasion of nucleosomes by transition proteins (TNP1 and TNP2) (PubMed:28366643). Then, transition proteins drive the recruitment and processing of protamines, which are responsible for histone eviction (PubMed:28366643). Also expressed maternally and is present in the female pronucleus, suggesting a similar role in protamine replacement by nucleosomes at fertilization (PubMed:23884607). Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. http://togogenome.org/gene/10090:Gbe1 ^@ http://purl.uniprot.org/uniprot/Q9D6Y9 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the glycosyl hydrolase 13 family. GlgB subfamily.|||Binds its carbohydrate substrate close to the active site, but also via regions close to the N-terminus; this may result in increased affinity and therefore increased catalytic efficiency.|||Monomer.|||Required for normal glycogen accumulation. The alpha 1-6 branches of glycogen play an important role in increasing the solubility of the molecule. http://togogenome.org/gene/10090:Rag2 ^@ http://purl.uniprot.org/uniprot/P21784|||http://purl.uniprot.org/uniprot/Q542D1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RAG2 family.|||Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.|||Core component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3.|||Maturing lymphoid cells.|||Mice are viable but fail to produce mature B or T-lymphocytes. Very immature lymphoid cells are present in primary lymphoid organs. These cells do not rearrange their immunoglobulin or T-cell receptor loci. Double knockout with TREX1 does not show a visible phenotype.|||Nucleus|||The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3). http://togogenome.org/gene/10090:Ly6g ^@ http://purl.uniprot.org/uniprot/P35461 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in bone marrow. http://togogenome.org/gene/10090:Atg4b ^@ http://purl.uniprot.org/uniprot/A0A0R4J065|||http://purl.uniprot.org/uniprot/Q8BGE6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C54 family.|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:14530254, PubMed:20577052, PubMed:29458288). Required for canonical autophagy (macroautophagy), non-canonical autophagy as well as for mitophagy (By similarity). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP, to reveal a C-terminal glycine (PubMed:14530254, PubMed:29458288). Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy (PubMed:14530254, PubMed:29458288). Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3 (By similarity). In addition to the protease activity, also mediates delipidation of ATG8 family proteins (PubMed:29458288). Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (By similarity). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) (By similarity). Compared to other members of the family (ATG4A, ATG4C or ATG4C), constitutes the major protein for proteolytic activation of ATG8 proteins, while it displays weaker delipidation activity than other ATG4 paralogs (PubMed:29458288). Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy (By similarity).|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.|||Cytoplasm|||Endoplasmic reticulum|||Forms reversible intrachain disulfide bonds in response to oxidative stress. Forms interchain disulfide bonds, leading to formation of homooligomers in response to oxidation.|||Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity. The cysteine protease activity compounds is inhibited by styrylquinoline compounds 4-28 and LV-320.|||Interacts with PFKP; promoting phosphorylation of ATG4B at Ser-34 (By similarity). Interacts with GBP7 (PubMed:21551061).|||Mice develop normally but are born at a slightly lower ratio than the expected Mendelian rate (PubMed:20577052, PubMed:20634410). Cells display systemic reduction of autophagic activity, characterized by defective proteolytic processing of ATG8 family proteins, compromising the rate of autophagosome maturation (PubMed:20577052). Mice show severe balance disorders, which are caused by defects in the development of otoconia (PubMed:20577052). The central nervous system (CNS) of mutant mice also displays amorphous globular bodies in the neuropil of the deep cerebellar nuclei and adjacent vestibular nuclei (PubMed:20634410). The spheroid-like bodies in the deep cerebellar and vestibular nuclei show heterogeneous composition, characteristics of proteinaceous material (PubMed:20634410).|||Mitochondrion|||O-glycosylated by OGT, leading to increase protease activity, thereby promoting the proteolytic activation of ATG8 family proteins.|||Phosphorylation at Ser-383 and Ser-392 promotes autophagy by increasing protein delipidation activity without affecting proteolytic activation of ATG8 proteins. Phosphorylation at Ser-316 by ULK1 inhibits autophagy by decreasing both proteolytic activation and delipidation activities. Phosphorylation at Ser-316 is dephosphorylated by protein phosphatase 2A (PP2A). Phosphorylation at Ser-34 by AKT2 promotes its hydrolase activity, leading to increased proteolytic activation and delipidation of ATG8 family proteins. Phosphorylation at Ser-34 by AKT1 promotes mitochondrial localization and inhibition of the F1F0-ATP synthase activity, leading to elevation of mitochondrial reactive oxygen species (ROS).|||S-nitrosylation at Cys-189 and Cys-292 in response to high glucose decreases both proteolytic activation and delipidation activities.|||The LIR motif (LC3-interacting region) is required for the interaction with ATG8 family proteins MAP1LC3A, MAP1LC3B, MAP1LC3C and GABARAPL1. Required for proteolytic activation and delipidation of ATG8 proteins.|||Ubiquitinated by RNF5, leading to its degradation by the proteasome.|||autophagosome|||cytosol http://togogenome.org/gene/10090:Rpl22 ^@ http://purl.uniprot.org/uniprot/P67984|||http://purl.uniprot.org/uniprot/Q4VAG4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL22 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Man2a1 ^@ http://purl.uniprot.org/uniprot/P27046 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All tissues, mostly in adrenal and thymus.|||Belongs to the glycosyl hydrolase 38 family.|||Binds 1 zinc ion per subunit.|||Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway.|||Glycosylated.|||Golgi apparatus membrane|||Homodimer; disulfide-linked. http://togogenome.org/gene/10090:Ccdc125 ^@ http://purl.uniprot.org/uniprot/Q5U465 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in many tissues, with highest levels in spleen, thymus and bone marrow.|||May be involved in the regulation of cell migration. http://togogenome.org/gene/10090:Peak1 ^@ http://purl.uniprot.org/uniprot/Q69Z38 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Has been the subject of controversy surrounding its catalytic capabilities. Early characterization of PEAK1 gave a weak in vitro tyrosine kinase activity. The crystal structure indicates that the kinase-domain contains a closed nucleotide-binding cleft that in this conformation may deleteriously affect nucleotide bindin. Furthermore PEAK1 is devoid of nucleotide binding activity, as detected by a thermal-shift assay. So it seems probable that PEAK1 is an inactive kinase.|||Homodimer (By similarity). Interacts with BCAR1 and CRK (By similarity). Interacts with PRAG1 (By similarity). Interacts (when phosphorylated at Tyr-1177) with SHC1 (via PID domain) (By similarity). Found in a complex with PPP1CA, PPP1CC and SHC1 (By similarity). Interacts (when phosphorylated at Tyr-632) with tensin TNS3 (when phosphorylated on the SH2 domain); TNS3 also interacts with integrins ITGB1, ITGB3 and ITGB5 and mediates their association with PEAK1 (PubMed:35687021).|||Phosphorylated on tyrosine in a CSK-dependent manner in response to adhesion to fibronectin and to EGF stimulation (PubMed:20534451). Phosphorylation at Tyr-662 by a Src family kinase controls subcellular localization to focal adhesion and focal adhesion dynamics. Phosphorylation at Tyr-1177 is essential for binding to SHC1. Phosphorylation at Tyr-632 promotes interaction with tensin TNS3.|||Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics. Acts as a scaffold for mediating EGFR signaling.|||The dimerization region encompasses helices both from the N- and C-terminal of the protein kinase domain.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Aatf ^@ http://purl.uniprot.org/uniprot/Q9JKX4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AATF family.|||Expressed in adrenal gland, brain (Purkinje cells), heart, kidney, liver, lung, muscle, ovary and testis (at the protein level).|||Expressed uniformly throughout the embryo until 10.5 dpc. From 11.5 dpc, the relative expression level increases in the liver, hind brain, spinal cord, dorsal root ganglia, and the posterior commissure.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with POLR2J, RB1/RB, RBL1/P107 and RBL2/P130. Interacts with PAWR and SP1. May also bind MAPT.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. May function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date.|||nucleolus http://togogenome.org/gene/10090:Tnfrsf13b ^@ http://purl.uniprot.org/uniprot/Q9ET35 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds TRAF2, TRAF5 and TRAF6. Binds the NH2-terminal domain of CAMLG with its C-terminus (By similarity).|||Membrane|||Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity. Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and AP-1. Involved in the stimulation of B- and T-cell function and the regulation of humoral immunity (By similarity). http://togogenome.org/gene/10090:Tmem79 ^@ http://purl.uniprot.org/uniprot/Q9D709 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Contributes to the epidermal integrity and skin barrier function. Plays a role in the lamellar granule (LG) secretory system and in the stratum corneum (SC) epithelial cell formation.|||Defects in Tmem79 are the cause of the spontaneous matted (matt) mutant phenotype, a model for human atopic dermatitis. Atopic dermatitis (ma/ma) mice have a matted hair phenotype with progressive dermatitis-like skin inflammation and a scratching behavior. Mice display an altered skin barrier that facilitates allergic sensitization.|||Expressed in the epidermis of the skin. Expressed in epithelial cells of the outermost layer of the stratum granulosum (SG) and in hair follicles (at protein level).|||Lysosome|||Membrane|||trans-Golgi network http://togogenome.org/gene/10090:Mbtps1 ^@ http://purl.uniprot.org/uniprot/Q9WTZ2 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S8 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor.|||Interacts with LYSET; this interaction bridges GNPTAB to MBTPS1.|||Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C. Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Catalyzes the first step regulated intramembrane proteolysis activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Also mediates the first step of the regulated intramembrane proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. Cleaves the propeptide from FAM20C which is required for FAM20C secretion from the Golgi apparatus membrane and for enhancement of FAM20C kinase activity, promoting osteoblast differentiation and biomineralization (PubMed:34349020). Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking. In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the first step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression (By similarity).|||The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates. http://togogenome.org/gene/10090:Gatad1 ^@ http://purl.uniprot.org/uniprot/Q920S3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a chromatin complex, at least composed of KDM5A, GATAD1 and EMSY.|||Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).|||Expressed in embryo at 13 dpc onwards. Expressed in embryonic heart at all stages of development.|||Expressed in the eye (lens, ciliary body, retina, sclera and conjunctiva) at postnatal day 2 and 10. Not detected anywhere at postnatal day 14.|||Nucleus http://togogenome.org/gene/10090:Yes1 ^@ http://purl.uniprot.org/uniprot/Q04736|||http://purl.uniprot.org/uniprot/Q3TJI7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Interacts with YAP1. Interacts with FASLG. Interacts with CTNND1; this interaction allows YES1-mediated activation of FYN and FER and subsequent phosphorylation of CTNND1 (By similarity). Interacts with CSF1R. Interacts with IL6ST/gp130 (By similarity).|||Knouckout mice show reduced OCT2 tyrosine phosphorylation and reduced OCT2-mediated TEA renal secretion (PubMed:26979622). Knouckout mice are protected from oxaliplatin-induced acute sensory neuropathy (PubMed:26979622). Mice are viable, fertile, and display no apparent phenotypes. This lack of phenotype may be attributable to compensatory roles of the other SRC-family members.|||Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis (By similarity). Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity (PubMed:26979622).|||Palmitoylation at Cys-3 promotes membrane localization.|||Phosphorylation by CSK on the C-terminal tail maintains the enzyme in an inactive state. Autophosphorylation at Tyr-424 maintains enzyme activity by blocking CSK-mediated inhibition (By similarity).|||centrosome|||cytosol http://togogenome.org/gene/10090:Arxes1 ^@ http://purl.uniprot.org/uniprot/C0HK79|||http://purl.uniprot.org/uniprot/C0HK80 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Arxes1 and Arxes2 appear to have arisen by retrotransposition of the signal peptidase Spcs3 followed by a segmental duplication event.|||Belongs to the SPCS3 family.|||By the PPARG agonist rosiglitazone.|||Endoplasmic reticulum membrane|||Plays a role in adipogenesis.|||Strongly expressed in epididymal white and brown adipose tissue with low levels in heart.|||Strongly up-regulated during adipogenesis. http://togogenome.org/gene/10090:Or4f52 ^@ http://purl.uniprot.org/uniprot/Q7TQY8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Agrn ^@ http://purl.uniprot.org/uniprot/M0QWP1 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Pja2 ^@ http://purl.uniprot.org/uniprot/Q80U04 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds ubiquitin-conjugating enzymes (E2s). In vitro, interacts with the ubiquitin-conjugating enzyme, UBE2D2. The phosphorylated form interacts with PRKAR1A, PRKAR2A and PRKAR2B. Binds the catalytic subunits of cAMP-dependent protein kinase. Interacts with MFHAS1. Interacts with TBC1D31; the interaction is direct and recruits PJA2 to centrosomes.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Has E2-dependent E3 ubiquitin-protein ligase activity. Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes. Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro-inflammatory M1 phenotype. Plays a role in ciliogenesis by ubiquitinating OFD1.|||Postsynaptic density|||Synapse|||centrosome http://togogenome.org/gene/10090:Sult4a1 ^@ http://purl.uniprot.org/uniprot/P63046 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Atypical sulfotransferase family member with very low affinity for 3'-phospho-5'-adenylyl sulfate (PAPS) and very low catalytic activity towards L-triiodothyronine, thyroxine, estrone, p-nitrophenol, 2-naphthylamine, and 2-beta-naphthol. May have a role in the metabolism of drugs and neurotransmitters in the CNS.|||Belongs to the sulfotransferase 1 family.|||Cytoplasm|||Expressed in brain, cerebellum and hypothalamus. Not detected in pancreas, liver, lung, intestine, kidney, uterus, adrenal gland, thymus, spleen, epididymis, testicle, and heart. http://togogenome.org/gene/10090:Ints11 ^@ http://purl.uniprot.org/uniprot/Q9CWS4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS11 subfamily.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Catalytic component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates the snRNAs 3' cleavage. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Cytoplasm|||Nucleus|||The HXHXDH motif is essential for the endoribonuclease activity of the CPSF complex. http://togogenome.org/gene/10090:Gpr55 ^@ http://purl.uniprot.org/uniprot/Q14BV9|||http://purl.uniprot.org/uniprot/Q3UJF0 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mutant mice are resistant to mechanical hyperalgesia and have increased levels of anti-inflammatory cytokines.|||Receptor for L-alpha-lysophosphatidylinositol (LPI). LPI induces Ca(2+) release from intracellular stores via the heterotrimeric G protein GNA13 and RHOA (By similarity). Putative cannabinoid receptor (By similarity). May play a role in bone physiology by regulating osteoclast number and function (By similarity). May be involved in hyperalgesia associated with inflammatory and neuropathic pain.|||The classification of this protein as a cannabinoid receptor remains a contentious issue due to conflicting pharmacological results. http://togogenome.org/gene/10090:Tmem95 ^@ http://purl.uniprot.org/uniprot/P0DJF3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM95 family.|||Does not interact with sperm-egg fusion proteins IZUMO1 or IZUMO1R/JUNO.|||Expressed exclusively in testis.|||Expression is first detected at postnatal day 21.|||Males are healthy, grossly normal and exhibit normal mating behavior but are infertile (PubMed:32484434, PubMed:32393636). Sperm are morphologically normal, exhibit normal motility and can penetrate the zona pellucida and bind to the oolemma but are unable to fuse with the egg membrane or penetrate into the ooplasm (PubMed:32484434, PubMed:32393636). No effect on location of sperm-egg fusion protein IZUMO1 (PubMed:32393636).|||Sperm protein required for fusion of sperm with the egg membrane during fertilization.|||acrosome membrane http://togogenome.org/gene/10090:Pcdhga7 ^@ http://purl.uniprot.org/uniprot/Q6DD96 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Plekhg2 ^@ http://purl.uniprot.org/uniprot/Q6KAU7 ^@ Function|||Tissue Specificity ^@ Expressed in thymus, skeletal muscle, lung, testis, uterus, pancreas and heart and also expressed during embryogenesis.|||May be a transforming oncogene with exchange activity for CDC42. May be a guanine-nucleotide exchange factor (GEF) for RAC1 and CDC42 (PubMed:11839748). Activated by the binding to subunits beta and gamma of the heterotrimeric guanine nucleotide-binding protein (G protein) (By similarity). Involved in the regulation of actin polymerization (By similarity). http://togogenome.org/gene/10090:Gm4847 ^@ http://purl.uniprot.org/uniprot/G3X946 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Dedd2 ^@ http://purl.uniprot.org/uniprot/Q8QZV0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expression is high in liver, heart, kidney, and testis but low in brain, spleen, lung, and skeleton muscle.|||Interactions with CASP8 and CASP10 are mediated by the DED domain.|||Interacts with CASP8, CASP10 and GTF3C3. Homodimerizes and heterodimerizes with DEDD (By similarity).|||May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the general transcription machinery in the nucleus and might be an important regulator of the activity of GTF3C3.|||nucleolus http://togogenome.org/gene/10090:Kel ^@ http://purl.uniprot.org/uniprot/Q9EQF2 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M13 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Heterodimer with XK; disulfide-linked.|||Highly expressed in spleen. Weaker expression in testis and heart.|||N-glycosylated.|||Zinc endopeptidase with endothelin-3-converting enzyme activity. Cleaves EDN1, EDN2 and EDN3 (By similarity). http://togogenome.org/gene/10090:Entpd1 ^@ http://purl.uniprot.org/uniprot/P55772|||http://purl.uniprot.org/uniprot/Q544U5|||http://purl.uniprot.org/uniprot/Q8CDV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GDA1/CD39 NTPase family.|||Homodimer; disulfide-linked.|||In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission. Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well.|||Membrane http://togogenome.org/gene/10090:Bcl7a ^@ http://purl.uniprot.org/uniprot/Q9CXE2 ^@ Miscellaneous|||Similarity ^@ Belongs to the BCL7 family.|||May be due to an intron retention. http://togogenome.org/gene/10090:Grm6 ^@ http://purl.uniprot.org/uniprot/A7MD55|||http://purl.uniprot.org/uniprot/Q5NCH9|||http://purl.uniprot.org/uniprot/Q8CFQ7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Detected in the outer plexiform layer in retina (at protein level).|||Endoplasmic reticulum membrane|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.|||Golgi apparatus membrane|||Homodimer (By similarity). Interacts with GPR179 (PubMed:24114537).|||Membrane|||Retinal cells from mutant mice display a subtly altered response to cycles of light and darkness, due to a failure of the ON bipolar cells in the retina to become depolarized in response to light. As a consequence, mutant mice display little or no pupillary contraction in adaptation to low light intensity. Besides, they exhibit strongly impaired responses to moving stimuli, and fail to produce a response when the visual constrast is low. Besides, rod bipolar cells from mutant mice lack TRPM1 channel activity.|||dendrite http://togogenome.org/gene/10090:Smad1 ^@ http://purl.uniprot.org/uniprot/P70340 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dwarfin/SMAD family.|||Cytoplasm|||Found in a complex with SMAD4 and YY1. Interacts with HGS, NANOG and ZCCHC12 (PubMed:11094085, PubMed:18160706). Upon C-terminus phosphorylation: forms trimers with another SMAD1 and the co-SMAD SMAD4 (By similarity). Interacts with PEBP2-alpha subunit, CREB-binding protein (CBP), p300, SMURF1, SMURF2, USP15 and HOXC8. Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with SKOR1. Interacts (via MH2 domain) with LEMD3. Binding to LEMD3 results in at least a partial reduction of receptor-mediated phosphorylation. Forms a ternary complex with PSMB4 and OAZ1 before PSMB4 is incorporated into the 20S proteasome. Found in a macromolecular complex with FAM83G. Interacts (via MH2 domain) with FAM83G (via MH2 domain); in a SMAD4-independent manner. Interacts with ZC3H3 (PubMed:16115198). Interacts with TMEM119 (PubMed:21239498). Interacts (via MH1 and MH2 domains) with ZNF8 (PubMed:12370310). Interacts with RANBP3L; the interaction increases when SMAD1 is not phosphorylated and mediates SMAD1 nuclear export (PubMed:25755279). Interacts with EGR1; this interaction inhibits SMAD1 dephosphorylation (PubMed:35594155). Interacts with SMAD6 (By similarity). Interacts with YAP1 (By similarity).|||Nucleus|||Phosphorylation of the C-terminal SVS motif by BMP type 1 receptor kinase activates SMAD1 by promoting dissociation from the receptor and trimerization with SMAD4. Phosphorylation by ERK2 MAP kinase in response to EGF or HGF prevents SMAD1 nuclear accumulation and transcriptional activity in response to BMP (By similarity). Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (PubMed:25755279). Dephosphorylation is inhibited by association with EGR1 (PubMed:35594155). Phosphorylation by CDK8/9 creates binding sites for YAP1, and subsequent phosphorylation by GSK3 switches off YAP1 binding and adds binding sites for SMURF1 (By similarity).|||SMAD1 deletion results in early embryonic lethality due to failure of the allantois to fuse to the chorion (PubMed:11566864). Chondrocyte-specific conditional knockout show a delay in calvarial bone mineralization and reduction of postnatal bone formation (PubMed:21420501).|||The MH2 domain mediates phosphorylation-dependent trimerization through L3 loop binding of phosphoserines in the adjacent subunit.|||Transcriptional modulator that plays a role in various cellular processes, including embryonic development, cell differentiation, and tissue homeostasis (PubMed:11566864, PubMed:15329343, PubMed:21420501, PubMed:35594155). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form an heteromeric complex which translocates into the nucleus acting as transcription factor. In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network. SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1 (By similarity). Positively regulates BMP4-induced expression of odontogenic development regulator MSX1 following IPO7-mediated nuclear import (PubMed:34995814).|||Ubiquitinated by SMAD-specific E3 ubiquitin ligase SMURF1, leading to its degradation. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes. Dephosphorylation, probably by PPM1A, induces its export from the nucleus to the cytoplasm (By similarity). Phospho-SMAD1 is ubiquitinated by CHIP leading to disruption of the SMAD1-SMAD4 complex (By similarity).|||Ubiquitous.|||Ubiquitously expressed during embryogenesis. Expression starts in some seminiferous tubules at 2 weeks of age. After mid-puberty a stage-specific expression is established. During the cycling of the seminiferous epithelium, expression initiates in the pachytene spermatocytes of stage V seminiferous tubules, peaks at stage X, then decreases as pachytene spermatocytes differentiate into secondary spermatocytes and then round spermatids. http://togogenome.org/gene/10090:Dtl ^@ http://purl.uniprot.org/uniprot/Q3TLR7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat cdt2 family.|||Chromosome|||Component of the DCX(DTL) E3 ubiquitin ligase complex (also called CRL4(CDT2)), at least composed of CUL4 (CUL4A or CUL4B), DDB1, DTL/CDT2 and RBX1 (By similarity). Interacts with CDKN1A and DDB1 (By similarity). Interacts with FBXO11; SCF(FBXWO11) controls DTL stability but DCX(DTL) does not control FBXO11 stability (By similarity). Interacts with CRY1 (By similarity).|||Early embryonic lethality due to cell cycle progression failure, termination of cell division, and, eventually, embryonic death during the preimplantation stage.|||Nucleus|||Nucleus membrane|||Phosphorylated at Thr-463 by CDK1/Cyclin B and CDK2/Cycnlin A but not by CDK2/Cyclin E, MAPK1 or PLK1. Phosphorylation at Thr-463 inhibits the interaction with FBXO11 and decreases upon cell cycle exit induced by TGF-beta or serum starvation (By similarity).|||Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis. The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (By similarity).|||Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C). Autoubiquitinated through 'Lys-48'-polyubiquitin chains in a PCNA-independent reaction, allowing proteasomal turnover. Polyubiquitinated by SCF(FBXO11) when not phosphorylated, leading to its degradation. A tight regulation of the polyubiquitination by SCF(FBXO11) is involved in the control of different processes such as TGF-beta signaling, cell cycle progression and exit (By similarity).|||centrosome http://togogenome.org/gene/10090:Fras1 ^@ http://purl.uniprot.org/uniprot/Q80T14 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FRAS1 family.|||Cell membrane|||Defects in Fras1 are the cause of blebbed (bl) phenotype, which is characterized by blister formation, syndactyly, eyelid fusion and renal agenesis. Subepidermal blisters are predominantly formed in the head region around the eyes and at the distal part of the limbs. As development proceeds blisters that are initially transparent gradually become hemorrhagic and embryos die between 14.5 dpc and 16.5 dpc.|||Highly expressed in the apical ectodermal ridge of the limb buds from 10.5-12.5 dpc and expression was also detected in the interdigital spaces at 14.5 dpc. Found in cells just underlying the surface epithelium of the entire embryo and in the linings of the peritoneal cavity and dorsal aorta. At 12 dpc, detected in the mesonephric duct and in the lens (PubMed:12766769). Found in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos (PubMed:12766770). Found in meningeal and choroidal epidermal-basement membranes in embryos and neonates (PubMed:32333816).|||Homozygous adult knockout mice display impaired performance in various types of learning and memory tasks as well as reduced anxiety.|||Involved in extracellular matrix organization (PubMed:32333816). Required for the regulation of epidermal-basement membrane adhesion responsible for proper organogenesis during embryonic development (PubMed:12766769). Involved in brain organization and function (PubMed:32333816).|||The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding. http://togogenome.org/gene/10090:Ovol1 ^@ http://purl.uniprot.org/uniprot/Q9WTJ2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in skin, testis, kidney and weakly in lung. Not detected in heart, brain, spleen, liver and skeletal muscle.|||First expressed at 14.5 dpc in the suprabasal layers of developing epidermis, at 15.5 dpc expression begins in the inner cells of developing hair germs and restricted to inner root sheath and/or precortical cells of developing hair follicles.|||Nucleus|||Putative transcription factor. Involved in hair formation and spermatogenesis. May function in the differentiation and/or maintenance of the urogenital system. http://togogenome.org/gene/10090:Acot11 ^@ http://purl.uniprot.org/uniprot/Q8VHQ9 ^@ Function|||Induction|||Subcellular Location Annotation ^@ By cold exposure and repressed by heat exposure.|||Cytoplasm|||Has an acyl-CoA thioesterase activity with a preference for the long chain fatty acyl-CoA thioesters hexadecanoyl-CoA/palmitoyl-CoA and tetradecanoyl-CoA/myristoyl-CoA which are the main substrates in the mitochondrial beta-oxidation pathway.|||Mitochondrion matrix http://togogenome.org/gene/10090:Map10 ^@ http://purl.uniprot.org/uniprot/Q8BJS7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts (via middle region) with microtubules.|||Microtubule-associated protein (MAP) that plays a role in the regulation of cell division; promotes microtubule stability and participates in the organization of the spindle midzone and normal progress of cytokinesis.|||Midbody|||centrosome|||cytoskeleton|||spindle pole http://togogenome.org/gene/10090:Rtp4 ^@ http://purl.uniprot.org/uniprot/Q9ER80 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM7 family.|||By interferons.|||Expressed at low levels in olfactory neurons.|||Interacts with TASR16 (By similarity). Interacts with OPRD1 and OPRM1; the interaction promotes cell surface localization of the OPDR1-OPRM1 heterodimer (PubMed:18836069).|||Membrane|||Probable chaperone protein which facilitates trafficking and functional cell surface expression of some G-protein coupled receptors (GPCRs). Promotes functional expression of the bitter taste receptor TAS2R16 (By similarity). Also promotes functional expression of the opioid receptor heterodimer OPRD1-OPRM1 (PubMed:18836069). http://togogenome.org/gene/10090:Bmp2 ^@ http://purl.uniprot.org/uniprot/P21274 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (at protein level) (PubMed:29148101).|||Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Also acts to promote expression of HAMP, via the interaction with its receptor BMPR1A/ALK3 (PubMed:31800957). Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation. Also stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (PubMed:29148101).|||Heterozygous BMP2-knockout mice show abnormal numbers of rib pairs, a reduction in overall body length, and less bone mineral content and volume than wild-type mice. Homozygous BMP2-knockout mice die before embryonic day 12.5.|||Homodimer; disulfide-linked. Interacts with SOSTDC1 (By similarity). Interacts with GREM2, RGMA, RGMB and RGMC. Interacts with ASPN (By similarity). Interacts with MAFP5 (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2. Interacts with type I receptor BMPR1A. Interacts with type II receptor BMPR2 (By similarity). Interacts with SCUBE3 (By similarity). Interacts with TNFAIP6 (primarily via Link domain); this interaction is inhibited by hyaluronan. Interacts with ERFE (PubMed:31800957). Interacts with BMPR1A/ALK3; the interaction may induce HAMP expression (PubMed:31800957). Forms heterodimers with BMP6 in vitro; the heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression (PubMed:31800957).|||Secreted http://togogenome.org/gene/10090:Dcn ^@ http://purl.uniprot.org/uniprot/P28654|||http://purl.uniprot.org/uniprot/Q3UKR1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.|||Binds to type I and type II collagen, fibronectin and TGF-beta. Forms a ternary complex with MFAP2 and ELN.|||Binds to type I and type II collagen, fibronectin and TGF-beta. Forms a ternary complex with MFAP2 and ELN. Interacts with DPT (By similarity).|||May affect the rate of fibrils formation.|||Secreted|||The attached glycosaminoglycan chain can be either chondroitin sulfate or dermatan sulfate depending upon the tissue of origin.|||extracellular matrix http://togogenome.org/gene/10090:Cdkn2a ^@ http://purl.uniprot.org/uniprot/P51480|||http://purl.uniprot.org/uniprot/Q64364 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.|||Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.|||By progesterone. Induced by activated Ras, and this requires DMTF1. Repressed by non-classical inhibitors of NF-kappa-B signaling such as doxorubicin, daunorubicin and UVC, and by the NF-kappa-B p65 subunit (RELA).|||Capable of inducing cell cycle arrest in G1 and G2 phases (PubMed:8521522, PubMed:9393858). Acts as a tumor suppressor (PubMed:8521522, PubMed:9393858, PubMed:15601844, PubMed:17936562). Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus (PubMed:9529248, PubMed:10359817). This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis (PubMed:10359817). Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes (PubMed:15361884). Binds to BCL6 and down-regulates BCL6-induced transcriptional repression (PubMed:15567177). Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression (By similarity). Binds to TOP1/TOPOI and stimulates its activity (By similarity). This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation (By similarity). Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing (By similarity). Plays a role in inhibiting ribosome biogenesis, perhaps by binding to the nucleolar localization sequence of transcription termination factor TTF1, and thereby preventing nucleolar localization of TTF1 (PubMed:20513429). Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination (By similarity). Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1 (By similarity). Binds to HUWE1 and represses its ubiquitin ligase activity (By similarity). May play a role in controlling cell proliferation and apoptosis during mammary gland development (By similarity).|||Cytoplasm|||Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or CDK6. Interacts with COMMD1 (By similarity). Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and UBE2I/UBC9. Interacts with TBRG1. Interacts with CDKN2AIP and E4F1. Interacts with CDK5RAP3 and MDM2; form a ternary complex involved in regulation of p53/TP53. Interacts with NOP53; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation (By similarity). Interacts with TTF1 (via the N-terminal region (NRD) and a C-terminal region); the interaction is direct and inhibits the nucleolar localization of TTF1 (PubMed:20513429).|||Heterodimer with CDK4 or CDK6. Predominamt P16 complexes contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity. Interacts with ISCO2 (By similarity).|||Interacts with C1QBP.|||May be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP.|||Mice lacking isoform tumor suppressor ARF of Cdkn2a display delayed mammary gland involution.|||Mitochondrion|||Not detected in 12-week virgin mammary glands. Expression increases (at protein level) six-fold during pregnancy and remains at this level during lactation. During involution, a slight increase is observed at days 2 and 8 followed by a sharp decline at day 15.|||Nucleus|||Phosphorylation seems to increase interaction with CDK4.|||Strain BALB/c displays a significantly reduced ability to inhibit phosphorylation of the retinoblastoma protein.|||The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in terms of sequence and function to cyclin-dependent kinase inhibitor 2A (AC P51480) which is encoded by the same gene.|||The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in terms of sequence and function to tumor suppressor ARF (AC Q64364) which is encoded by the same gene.|||Ubiquitinated in normal cells by TRIP12 via the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination at the N-terminus, regardless of the absence of lysine residues. Ubiquitination leads to its proteasomal degradation. In cancer cells, however, TRIP12 is located in a different cell compartment, preventing ubiquitination and degradation.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Podxl ^@ http://purl.uniprot.org/uniprot/Q791G4|||http://purl.uniprot.org/uniprot/Q9R0M4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the podocalyxin family.|||Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with NHERF1 and for targeting NHERF1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation (By similarity).|||Cell membrane|||Die within the first 24 hours of postnatal life from profound defects in kidney and/or gut formation. They are anuric (no measurable urine in the bladder), and fail to generate the extensive interdigitated foot process and instead retain cell junctions between immature podocytes.|||Expressed in liver cells and hematopoietic cells (at protein level). Glomerular epithelium cell (podocyte).|||Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells.|||Membrane|||Membrane raft|||Monomer; when associated with the membrane raft. Oligomer; when integrated in the apical membrane. Found in a complex with EZR, PODXL and NHERF2. Associates with the actin cytoskeleton through complex formation with EZR and NHERF2. Interacts (via the C-terminal PDZ-binding motif DTHL) with NHERF1 (via the PDZ domains); interaction is not detected in glomerular epithelium cells, take place early in the secretory pathway and is necessary for its apical membrane sorting. Interacts (via the C-terminal PDZ-binding motif DTHL) with NHERF2 (via the PDZ 1 domain); interaction is detected in glomerular epithelium cells. Interacts with EZR (By similarity).|||N- and O-linked glycosylated. Sialoglycoprotein (By similarity).|||filopodium|||lamellipodium|||microvillus|||ruffle http://togogenome.org/gene/10090:Tmprss6 ^@ http://purl.uniprot.org/uniprot/Q9DBI0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s).|||Expressed at higher levels from 12.5 dpc to 15.5 dpc with a peak at 13.5 dpc. Expressed in the developing liver and at lower levels in developing pharyngo-tympanic tubes.|||Expressed at highest levels in adult mice liver, kidney and uterus. Also strongly expressed within the nasal cavity by olfactory epithelial cells. A weak, but detectable, signal in adult mice tissues analyzed including brain, lung, heart, kidney, spleen, muscle, intestine, thymus and pancreas. No signal in residual embryonic yolk sac, developing kidney tubules or in embryonic tissues analyzed including lung, heart, gastrointestinal tract and epithelium of the oral cavity.|||Interacts with HJV.|||Membrane-bound serine protease (PubMed:18451267). Through the cleavage of cell surface HJV, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis (PubMed:18451267).|||Mice display the phenotype named mask, characterized by progressive loss of body (but not facial) hair, microcytic anemia and female infertility, all reversible by dietary iron supplementation. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin.|||The single-chain zymogen undergoes autoproteolytic processing. This results in TMPRSS6 shedding from the cell surface and conversion into an activated two-chains form which is released extracellularly. The process involves a trans-activation mechanism that requires TMPRSS6 oligomerization. http://togogenome.org/gene/10090:Mettl18 ^@ http://purl.uniprot.org/uniprot/Q9CZ09 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METTL18 family.|||Interacts with GRWD1 and members of the heat shock protein 90 and 70 families; these proteins may possibly be methylation substrates for the enzyme.|||Monomethylated at His-144 through automethylation. Automethylation at His-144 positively regulates the methyltransferase activity toward RPL3. Probably methylated on other residues.|||Nucleus|||Protein-L-histidine N-tele-methyltransferase that specifically monomethylates RPL3, thereby regulating translation elongation. Histidine methylation of RPL3 regulates translation elongation by slowing ribosome traversal on tyrosine codons: slower elongation provides enough time for proper folding of synthesized proteins and prevents cellular aggregation of tyrosine-rich proteins.|||cytosol|||nucleolus http://togogenome.org/gene/10090:Aicda ^@ http://purl.uniprot.org/uniprot/Q9WVE0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytidine and deoxycytidylate deaminase family.|||Cytoplasm|||Expressed in germinal center B-cells (at protein level).|||Interacts with CTNNBL1; the interaction is important for the immunoglobulin switch activity of AICDA. Interacts (via its NLS) with KPNA1. Interacts with PKA/PRKACA and PRKAR1A/PKR1 (By similarity). Interacts with SUPT6H, TRIM28 and NCL. Directly interacts with MCM3AP/GANP; this interaction may favor AICDA recruitment to immunoglobulin variable region genes, hence promoting somatic hypermutations (PubMed:20507984).|||Nucleus|||Probably monoubiquitinated on several residues by RNF126.|||Ser-38 is the major site whereas Thr-27 is the minor site of phosphorylation. Phosphorylation regulates its class-switch recombination activity (By similarity).|||Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. http://togogenome.org/gene/10090:Npy2r ^@ http://purl.uniprot.org/uniprot/P97295|||http://purl.uniprot.org/uniprot/Q3SWR9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for neuropeptide Y and peptide YY. http://togogenome.org/gene/10090:Glb1l ^@ http://purl.uniprot.org/uniprot/Q8VC60 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 35 family.|||Probable glycosyl hydrolase.|||Secreted http://togogenome.org/gene/10090:Nox3 ^@ http://purl.uniprot.org/uniprot/Q672J9 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by the ototoxic drug cisplatin. Activated by NOXO1. Cooperatively activated by NCF1 and NCF2 or NOXA1 in a phorbol 12-myristate 13-acetate (PMA)-dependent manner. Inhibited by diphenyleneiodonium chloride.|||Expressed in fetal kidney.|||Interacts with and stabilizes CYBA/p22phox.|||Membrane|||Mice display balance defects, a tilted position of the head and abnormal performances in motor coordination tests. This is associated with the absence of otoconia in both the utricle and saccule of the inner ear.|||NADPH oxidase which constitutively produces superoxide upon formation of a complex with CYBA/p22phox. Plays a role in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity.|||Specifically expressed in inner ear by the spiral glanglion neurons, the vestibular system and the sensory epithelial cell layer of the saccule. Weakly expressed in skull and brain. http://togogenome.org/gene/10090:Nat9 ^@ http://purl.uniprot.org/uniprot/Q3UG98 ^@ Function|||Similarity ^@ Belongs to the acetyltransferase family. GNAT subfamily.|||N-acetyltransferase that mediates the acetylation of the N-terminal residues of alpha- and beta-tubulin. http://togogenome.org/gene/10090:Pou2f1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Z4|||http://purl.uniprot.org/uniprot/E9Q6Z8|||http://purl.uniprot.org/uniprot/F8VQL7|||http://purl.uniprot.org/uniprot/P25425 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family. Class-2 subfamily.|||Interacts with POU2AF1; the interaction increases POU2F1 transactivation activity. Interacts with NR3C1, AR, PGR and HCFC1.|||Nucleus|||Phosphorylated by PRKDC.|||Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR.|||Ubiquitously expressed. However, isoforms 4 and 5 are only expressed in lymphocytes. http://togogenome.org/gene/10090:Psmd10 ^@ http://purl.uniprot.org/uniprot/Q9Z2X2 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module (By similarity). Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.|||Acts as an oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export (By similarity).|||Cytoplasm|||Nucleus|||Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex (By similarity). Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK (By similarity).|||Up-regulated by activated HRAS. http://togogenome.org/gene/10090:Hgd ^@ http://purl.uniprot.org/uniprot/O09173 ^@ Disease Annotation|||Function|||Similarity|||Subunit ^@ Belongs to the homogentisate dioxygenase family.|||Catalyzes the conversion of homogentisate to maleylacetoacetate.|||Defects in Hgd are the cause of alkaptonuria (aku). Aku is an autosomal recessive error of metabolism which is characterized by an increase in the level of homogentisic acid.|||Homohexamer arranged as a dimer of trimers. http://togogenome.org/gene/10090:Bmp1 ^@ http://purl.uniprot.org/uniprot/P98063 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activity is increased by the procollagen C-endopeptidase enhancer protein.|||At high levels in embryonic maternal deciduum and floor plate region of the neural tube. Less in developing membranous and endochondral bone, submucosa of intestine, dermis of skin and the mesenchyme of spleen and lung.|||Binds 1 zinc ion per subunit.|||Deletion mice are perinatally lethal, with the most obvious gross abnormality being failure of ventral body wall closure, and persistent herniation of the gut. This phenotype likely reflects the defective and weakened nature of extracellular matrix (ECM) in these embryos (PubMed:8951074). Double knockout mice (BMP1 and TLL1) display progressive defects in teeth and bone development (PubMed:28068493, PubMed:24419319).|||Interacts with POSTN, the interaction promotes deposition on the extracellular matrix.|||Metalloprotease that plays key roles in regulating the formation of the extracellular matrix (ECM) via processing of various precursor proteins into mature functional enzymes or structural proteins. Thereby participates in several developmental and physiological processes such as cartilage and bone formation, muscle growth and homeostasis, wound healing and tissue repair (PubMed:24419319, PubMed:8951074, PubMed:28068493). Roles in ECM formation include cleavage of the C-terminal propeptides from procollagens such as procollagen I, II and III or the proteolytic activation of the enzyme lysyl oxidase LOX, necessary to formation of covalent cross-links in collagen and elastic fibers (PubMed:20181949). Additional substrates include matricellular thrombospondin-1/THBS1 whose cleavage leads to cell adhesion disruption and TGF-beta activation (By similarity).|||Secreted|||extracellular matrix|||trans-Golgi network http://togogenome.org/gene/10090:Noc3l ^@ http://purl.uniprot.org/uniprot/Q8VI84 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CBF/MAK21 family.|||Induced between 1 and 12 hours following adipogenic stimulus.|||May be required for adipogenesis.|||Nucleus speckle|||nucleolus http://togogenome.org/gene/10090:Zar1 ^@ http://purl.uniprot.org/uniprot/Q80SU3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZAR1 family.|||Cytoplasm|||Cytoplasmic ribonucleoprotein granule|||Disordered region at the N-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes.|||Expressed in zygote at the one-cell embryo, markedly less abundant at the two-cell embryo.|||Interacts with YBX2.|||Mice are viable but females are infertile (PubMed:12539046). Ovarian development and oogenesis through the early stages of fertilization are normal, but most embryos from mutant females arrest at the one-cell stage (PubMed:12539046, PubMed:36264786). Abolished formation of MARDO phase-separated membraneless compartment and mitochondrial clustering in oocytes (PubMed:36264786). Mice lacking Zar1 and Zar1l oocytes display delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy (PubMed:31598710). The grown oocytes of Zar1 and Zar1l mutant mice contain decreased levels of many maternal mRNAs and display a reduced level of protein synthesis (PubMed:31598710).|||Ovary (PubMed:12539046, PubMed:12773403). Expressed in primary oocytes (from primary through antral follicle stages) and during the progression from Meiosis I to Meiosis II (PubMed:12539046, PubMed:12773403, PubMed:31598710). The mRNA is detected in growing oocytes (early primary follicle, type 3a) through fully grown oocytes (antral follicle, type 8) (PubMed:12539046, PubMed:12773403).|||Phosphorylation by CDK1 does not regulate formation of MARDO (mitochondria-associated ribonucleoprotein domain) membraneless compartment.|||The 3CxxC-type mediates binding to the 3'-UTR of mRNAs.|||Ubiquitinated and degradaded by the proteasome during oocyte meiotic maturation, leading to MARDO (mitochondria-associated ribonucleoprotein domain) membraneless compartment dissolution.|||mRNA-binding protein that mediates formation of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes (PubMed:36264786). MARDO assembly around mitochondria is directed by an increase in mitochondrial membrane potential during oocyte growth (PubMed:36264786). Promotes formation of MARDO phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to maternal mRNAs (PubMed:36264786). Binds to the 3'-UTR of maternal mRNAs (PubMed:31598710). Maternal mRNAs stored in the MARDO are translationally repressed (PubMed:36264786). Essential for female fertility and oocyte-to-embryo transition by coordinating maternal mRNA storage, translation and degradation (PubMed:12539046, PubMed:31598710, PubMed:36264786). http://togogenome.org/gene/10090:Foxp3 ^@ http://purl.uniprot.org/uniprot/Q53Z59|||http://purl.uniprot.org/uniprot/Q99JB6 ^@ Disease Annotation|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions (PubMed:22312127). Acetylation is mediated by a coordinated action of KAT5 and EP300/p300 acetyltransferases: EP300/p300 is required to enhance KAT5 autoacetylation, promoting acetylation of FOXP3 by KAT5 (By similarity). Deacetylated by SIRT1 (PubMed:22312127).|||By TGFB1 in T-cells. Down-regulated in regulatory T-cells (Treg) during inflammation.|||Cytoplasm|||Defects in Foxp3 are the cause of the scurfy phenotype (sf). It results in a lethal disorder of immunoregulation, characterized by infections, diarrhea, anemia, thrombocytopenia, hypogonadism, gastrointestinal bleeding, lymphadenopathy and leukocytosis.|||High level of expression in thymus and spleen.|||Homodimer (PubMed:22813742). Dimerization is essential for its transcriptional regulator activity. Interacts with IKZF3 (By similarity). Interacts (via LXXLL motif) with isoform 4 of RORA (via AF-2 motif) (By similarity). Interacts with STUB1 and HSPA1A/B. Interacts with IKZF4, HDAC7 and KAT5. Interacts with RUNX1, RUNX2, RUNX3 and NFATC2. Interacts with RORC. Interacts with HDAC9 in the absence of T-cell stimulation (By similarity). Interacts with RELA, PPP1CA, PPP1CB, PPP1CG, HSPA8 and USP7 (By similarity).|||Nucleus|||Phosphorylation at Ser-418 regulates its transcriptional repressor activity and consequently, regulatory T-cells (Treg) suppressive function (By similarity). Phosphorylation by CDK2 negatively regulates its transcriptional activity and protein stability.|||Polyubiquitinated, leading to its proteasomal degradation in regulatory T-cells (Treg) which is mediated by STUB1 in a HSPA1A/B-dependent manner. Deubiquitinated by USP7 and USP44 leading to increase in protein stability.|||The fork-head DNA-binding domain is essential for its dimerization and interaction with NFATC2.|||Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg) (PubMed:22813742). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (By similarity). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (By similarity). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (PubMed:19696312).|||Undergoes proteolytic cleavage in activated regulatory T-cells (Treg), and can be cleaved at either the N- or C-terminal site, or at both sites. Treg expressing the form cleaved at C-terminal site or both N- and C-terminal sites exhibit an increased induction of IL10 and an increased capacity to suppress proliferation of conventional T-cells in vitro. Treg expressing the form cleaved at only the C-terminal site are highly effective at preventing experimental colitis in an in vivo model of inflammatory bowel disease. http://togogenome.org/gene/10090:Vwde ^@ http://purl.uniprot.org/uniprot/Q6DFV8 ^@ Caution|||Subcellular Location Annotation ^@ Despite its name, this protein does not contain any EGF-like domains. The human ortholog has a much longer C-terminus which contains a number of EGF-like domains but there is currently no evidence for this region in mouse.|||Secreted http://togogenome.org/gene/10090:Wfdc12 ^@ http://purl.uniprot.org/uniprot/Q9JHY3 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Antibacterial protein which inhibits the growth of E.coli and S.aureus. Putative acid-stable proteinase inhibitor.|||Constitutively expressed in tongue.|||Secreted http://togogenome.org/gene/10090:Calcr ^@ http://purl.uniprot.org/uniprot/Q60755 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Interacts with GPRASP2.|||This is a receptor for calcitonin. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The calcitonin receptor is thought to couple to the heterotrimeric guanosine triphosphate-binding protein that is sensitive to cholera toxin. http://togogenome.org/gene/10090:Kcnj15 ^@ http://purl.uniprot.org/uniprot/O88932|||http://purl.uniprot.org/uniprot/Q3TNE6|||http://purl.uniprot.org/uniprot/Q53Z04 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ15 subfamily.|||Expressed in the proximal segment of the nephron.|||Interacts with PATJ.|||Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium.|||Membrane http://togogenome.org/gene/10090:Ankle2 ^@ http://purl.uniprot.org/uniprot/Q6P1H6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ANKLE2 family.|||Endoplasmic reticulum membrane|||Interacts with BAF/BANF1. Interacts with protein phosphatase 2A (PP2A) components PPP2C (PPP2CA or PPP2CB) and PPP2R1A (By similarity).|||Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit. Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly. May regulate nuclear localization of VRK1 in non-dividing cells. It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex. Involved in brain development. http://togogenome.org/gene/10090:Cyp4f18 ^@ http://purl.uniprot.org/uniprot/Q99N16 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of the pro-inflammatory lipid mediator leukotriene B4 (LTB4) (PubMed:16380383, PubMed:24632148). Hydroxylates at the omega-1 and omega-2 positions LTB4. This oxidation step leads to LTB4 inactivation, which is postulated to be a crucial part of the resolution of inflammation (PubMed:16380383, PubMed:24632148). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:16380383, PubMed:24632148).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highest level in polymorphonuclear leukocytes and dendritic cells. Detectable in lymph nodes, spleen, bone marrow and peripheral blood. Highly expressed in ovary. Very low level in liver, kidney, and smooth muscle. Expressed in neutrophils (at protein level).|||Mice are born at the expected Mendelian rate. No visible phenotype.|||Microsome membrane|||Up-regulated in bone marrow-derived dendritic cells by bacterial lipopolysaccharide (LPS), a ligand for toll-like receptor 4 (TLR4), and by poly(I:C), a ligand for TLR3. http://togogenome.org/gene/10090:Or7e173 ^@ http://purl.uniprot.org/uniprot/Q8VFI7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ly96 ^@ http://purl.uniprot.org/uniprot/Q9JHF9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds bacterial lipopolysaccharide (LPS) (PubMed:22532668). Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both LY96 and TLR4, but not TLR4 alone, respond to LPS (PubMed:10725698).|||Heterogeneous homomer formed from homodimers; disulfide-linked (By similarity). Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (PubMed:10725698, PubMed:20133493, PubMed:24380872). Binds to the extracellular domain of TLR4 (PubMed:10725698, PubMed:20133493, PubMed:24380872, PubMed:17803912, PubMed:22532668). Binds to the extracellular domain of TLR2 (By similarity). Ligand binding induces interaction with TLR4 and oligomerization of the complex (PubMed:20133493, PubMed:24380872, PubMed:22532668).|||Highly expressed in spleen, bone marrow, thymus, liver, kidney, ovary and decidua. Detected at lower levels in testis, small intestine and skin.|||N-glycosylated.|||Secreted|||extracellular space http://togogenome.org/gene/10090:Pspn ^@ http://purl.uniprot.org/uniprot/A1L3Q1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TGF-beta family. GDNF subfamily.|||Secreted http://togogenome.org/gene/10090:Mrpl27 ^@ http://purl.uniprot.org/uniprot/Q99N92 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL27 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Tnfsfm13 ^@ http://purl.uniprot.org/uniprot/Q5F2A1|||http://purl.uniprot.org/uniprot/Q8BXS2 ^@ Similarity ^@ Belongs to the tumor necrosis factor family. http://togogenome.org/gene/10090:Acsf2 ^@ http://purl.uniprot.org/uniprot/Q8VCW8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acyl-CoA synthases catalyze the initial reaction in fatty acid metabolism, by forming a thioester with CoA. Has some preference toward medium-chain substrates. Plays a role in adipocyte differentiation.|||Belongs to the ATP-dependent AMP-binding enzyme family.|||Mitochondrion http://togogenome.org/gene/10090:Sox9 ^@ http://purl.uniprot.org/uniprot/Q04887 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated; acetylation impairs nuclear localization and ability to transactivate expression of target genes (PubMed:26910618). Deacetylated by SIRT1 (PubMed:26910618).|||Expressed in the intestinal epithelium (at protein level) (PubMed:22510880). Expressed in progenitor cells in various organs, including chondroprogenitors, osteoprogenitors and preadipocytes, but is not expressed in most differentiated cell types such as osteoblasts and adipocytes, with the exception of chondrocytes (PubMed:16203988). Highly expressed in developing chondrogenic tissues (PubMed:9119111). Also expressed in some non-chondrogenic tissues such as notochord, otic vesicle and neural tube (PubMed:9119111).|||Homodimer; homodimerization is required for activity (PubMed:26146088). Interacts (via C-terminus) with ZNF219; forming a complex that binds to the COL2A1 promoter and activates COL2A1 expression (PubMed:20940257). Interacts with DDRGK1 (By similarity). Interacts with EP300/p300 (By similarity). Interacts with beta-catenin (CTNNB1); inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1 (PubMed:15132997).|||Nucleus|||Perinatal lethality, with cleft palate, as well as hypoplasia and bending of many skeletal structures derived from cartilage precursors (PubMed:11371614). Heterozygous mice die shortly after birth and display skeletal malformations caused by impaired precartilaginous condensations (PubMed:11371614). In embryonic day 12.5 dpc heterozygotes embryos, skeletal elements are smaller (PubMed:11371614, PubMed:11857796). In 14.5 dpc heterozygous embryos, bending of radius, ulna and tibia cartilages is already prominent (PubMed:11371614). Premature mineralization is observed in many bones, including vertebrae and some craniofacial bones in 18.5 dpc heterozygous embryos (PubMed:11371614). Conditional deletion in undifferentiated mesenchymal cells of limb buds before mesenchymal condensations results in a complete absence of both cartilage and bone, while markers for the different axes of limb development show a normal pattern of expression (PubMed:12414734). Conditional deletion in undifferentiated mesenchymal cells of limb buds after chondrogenic mesenchymal condensations causes a severe generalized chondrodysplasia, in which most prechondrocytes are arrested as condensed mesenchymal cells and do not undergo overt differentiation into chondrocytes (PubMed:12414734). Conditional deletion in differentiated growth plate chondrocytes results in severe dwarfism caused by shortened columnar zones in growth plates, leading to an absence of chondrocyte enlargement (PubMed:22421045). Conditional deletion in epithelial cells leads to severe branching defects in the lung (PubMed:24191021).|||Phosphorylation at Ser-64 and Ser-211 by PKA increases transcriptional activity and may help delay chondrocyte maturation downstream of PTHLH/PTHrP signaling (PubMed:10805756, PubMed:11120880). Phosphorylation at either Ser-64 or Ser-211 is required for sumoylation, but phosphorylation is not dependent on sumoylation (PubMed:29644115). Phosphorylated on tyrosine residues; tyrosine dephosphorylation by PTPN11/SHP2 blocks SOX9 phosphorylation by PKA and subsequent SUMOylation (PubMed:29644115).|||Predominantly expressed in mesenchymal condensations throughout the embryo before and during the deposition of cartilage (PubMed:7704017). Expressed in multipotent skeletogenic cells (PubMed:9119111). Continues to be expressed during chondrocyte lineage progression, except in terminally differentiating growth plate chondrocytes (PubMed:9119111). Also expressed in some non-chondrogenic tissues such as notochord, otic vesicle and neural tube (PubMed:9119111). In the developing lung, expressed at the distal tips of the branching epithelium as branching occurs and is down-regulated starting at embryonic day (E)16.5, at the onset of terminal differentiation of type 1 and type 2 alveolar cells (PubMed:24191021).|||Sumoylated; phosphorylation at either Ser-64 or Ser-211 is required for sumoylation (PubMed:29644115). Sumoylation is induced by BMP signaling pathway (PubMed:29644115).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||The PQA region (for proline, glutamine and alanine-rich) helps stabilize SOX9 and facilitates transactivation. It lacks intrinsic transactivation capability.|||The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.|||Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:10319868, PubMed:11371614, PubMed:12414734, PubMed:15132997, PubMed:18415932, PubMed:20940257, PubMed:28263186). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes COL2A1, COL4A2, COL9A1, COL11A2 and ACAN, SOX5 and SOX6 (PubMed:9119111, PubMed:10805756, PubMed:12414734, PubMed:15694126, PubMed:17525254, PubMed:26146088, PubMed:26150426, PubMed:26910618, PubMed:28263186). Also binds to some promoter regions (PubMed:20940257). Plays a central role in successive steps of chondrocyte differentiation (PubMed:11371614, PubMed:12414734, PubMed:22421045). Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes (PubMed:11371614, PubMed:12414734). Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis (PubMed:11371614, PubMed:12414734, PubMed:15529345). Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes by lowering beta-catenin (CTNNB1) signaling and RUNX2 expression (PubMed:22421045, PubMed:31121357). Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells and transactivating COL10A1 along with MEF2C (PubMed:21367821, PubMed:22421045). Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO (FOXO1 and FOXO3) transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (PubMed:32103177). Mechanistically, helps, but is not required, to remove epigenetic signatures of transcriptional repression and deposit active promoter and enhancer marks at chondrocyte-specific genes (PubMed:30021842). Acts in cooperation with the Hedgehog pathway-dependent GLI (GLI1 and GLI3) transcription factors (PubMed:29659575). In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells: involved in the lung epithelium during branching morphogenesis, by balancing proliferation and differentiation and regulating the extracellular matrix (PubMed:24191021). Controls epithelial branching during kidney development (PubMed:21212101).|||Ubiquitinated; ubiquitination leads to proteasomal degradation and is negatively regulated by DDRGK1.|||Upon lipid starvation conditions, expression is activated by FOXO (FOXO1 and FOXO3). http://togogenome.org/gene/10090:Rnf157 ^@ http://purl.uniprot.org/uniprot/A2AAN9 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||E3 ubiquitin ligase. http://togogenome.org/gene/10090:Slc5a8 ^@ http://purl.uniprot.org/uniprot/Q8BYF6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactate, pyruvate, acetate, propionate, valerate and butyrate), mocarboxylate drugs (nicotinate, benzoate, salicylate and 5-aminosalicylate) and ketone bodies (beta-D-hydroxybutyrate, acetoacetate and alpha-ketoisocaproate), with a Na(+):substrate stoichiometry of between 4:1 and 2:1 (PubMed:15322102, PubMed:15651982, PubMed:20211600). Catalyzes passive carrier mediated diffusion of iodide (By similarity). Mediates iodide transport from the thyrocyte into the colloid lumen through the apical membrane (By similarity). May be responsible for the absorption of D-lactate and monocarboxylate drugs from the intestinal tract (By similarity). May play a critical role in the entry of L-lactate and ketone bodies into neurons by a process driven by an electrochemical Na(+) gradient and hence contribute to the maintenance of the energy status and function of neurons (By similarity). Mediates sodium-coupled electrogenic transport of pyroglutamate (5-oxo-L-proline) (PubMed:20211600). Can mediate the transport of chloride, bromide, iodide and nitrate ions when external concentration of sodium ions is reduced (By similarity).|||Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Expressed in brain, colon, kidney and in the ileum and jejunum of small intestine. In the kidney, expression occurred in the proximal tubule and the loop of Henle, being restricted to tubular epithelial cells in both the cortex and the medulla. In the colon, predominantly expressed in the distal half of the large bowel and in the most terminal ileum. Localized selectively in the luminal surface of crypts in the large intestine and to the brush border in the middle parts of crypts in the cecum. In the brain, expression was seen throughout, exclusively in neurons, including the cortex, hippocampus, cerebellum and pituitary gland (at protein level). Expression is reduced in oligodendrogliomas.|||Interacts (via PDZ-binding motif) with PDZK1 (via PDZ domains 1 and 3); interaction increases nicotinate transport activity of SLC5A8.|||Transport of D-lactate and pyruvate stimulated by alpha-cyano-4-hydroxycinnamic acid, but inhibited by the short-chain fatty acids acetate, propionate and butyrate. http://togogenome.org/gene/10090:Slc3a1 ^@ http://purl.uniprot.org/uniprot/Q91WV7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a chaperone that facilitates biogenesis and trafficking of functional transporter heteromers to the plasma membrane (By similarity) (PubMed:26739563). Associates with SLC7A9 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. SLC7A9-SLC3A1 transporter has system b(0,+)-like activity with high affinity for extracellular cationic amino acids and L-cystine and lower affinity for intracellular neutral amino acids. Substrate exchange is driven by high concentration of intracellular neutral amino acids and the intracellular reduction of L-cystine to L-cysteine. SLC7A9-SLC3A1 acts as a major transporter for reabsorption of L-cystine and dibasic amino acids across the brush border membrane in early proximal tubules (By similarity). Associates with SLC7A13 to form a functional complex that transports anionic and neutral amino acids via exchange or facilitated diffusion. SLC7A13-SLC3A1 may act as a major transporter for L-cystine in late proximal tubules, ensuring its reabsorption from the luminal fluid in exchange for cytosolic L-glutamate or L-aspartate (PubMed:26739563).|||Apical cell membrane|||Cell membrane|||Disulfide-linked heterodimer composed of the catalytic light subunit SLC7A9 and the heavy subunit SLC3A1. The heterodimer is the minimal functional unit. Assembles in non-covalently linked heterotetramers (dimers of heterodimers) and higher order oligomers; the oligomerization is mediated by SLC3A1 likely to prevent degradation in the endoplasmic reticulum and facilitate heteromer trafficking to the plasma membrane (By similarity) (PubMed:12167606). Disulfide-linked heterodimer composed of the catalytic light subunit SLC7A13 and the heavy subunit SLC3A1 (PubMed:26739563).|||Expressed in the brush border membrane in the kidney (at protein level). Highly expressed in renal tubules in the outer stripe of the outer medulla and medullary ray (at protein level). Also detected in the renal cortex. More abundant in male than female kidneys. http://togogenome.org/gene/10090:Acot5 ^@ http://purl.uniprot.org/uniprot/Q6Q2Z6|||http://purl.uniprot.org/uniprot/Q91YQ6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16940157). Mainly active on medium-chain acyl-CoAs (PubMed:15007068). Seems to be involved in intraperoxisomal regulation of acyl-CoA levels, but not CoASH levels (PubMed:15007068). May have a function in termination of beta-oxidation of fatty acids (PubMed:15007068).|||Highly expressed in spleen, brain, testis and proximal and distal intestine; expressed at low level in the liver.|||In the liver and kidney, by peroxisome proliferator, via the peroxisome proliferator-activated receptors (PPARs) and by fasting.|||Peroxisome http://togogenome.org/gene/10090:Jakmip3 ^@ http://purl.uniprot.org/uniprot/Q5DTN8 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the JAKMIP family.|||Due to intron retention.|||Golgi apparatus http://togogenome.org/gene/10090:Dscc1 ^@ http://purl.uniprot.org/uniprot/Q14AI0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DCC1 family.|||Component of the CTF18-RFC complex which consists of CTF8, CTF18, DSCC1 and the RFC complex. Interacts with CTF8 and CTF18. Interacts with DDX11.|||Loads PCNA onto primed templates regulating velocity, spacing and restart activity of replication forks. May couple DNA replication to sister chromatid cohesion through regulation of the acetylation of the cohesin subunit SMC3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Haus3 ^@ http://purl.uniprot.org/uniprot/Q8QZX2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS3 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||centrosome|||spindle http://togogenome.org/gene/10090:4932429P05Rik ^@ http://purl.uniprot.org/uniprot/A2ADI4 ^@ Similarity ^@ Belongs to the SMEK family. http://togogenome.org/gene/10090:Plekhg3 ^@ http://purl.uniprot.org/uniprot/Q4VAC9 ^@ Function|||Subcellular Location Annotation ^@ Plays a role in controlling cell polarity and cell motility by selectively binding newly polymerized actin and activating RAC1 and CDC42 to enhance local actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Hmbs ^@ http://purl.uniprot.org/uniprot/P22907|||http://purl.uniprot.org/uniprot/Q3UBC6|||http://purl.uniprot.org/uniprot/Q3UPG1 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ As part of the heme biosynthetic pathway, catalyzes the sequential polymerization of four molecules of porphobilinogen to form hydroxymethylbilane, also known as preuroporphyrinogen. Catalysis begins with the assembly of the dipyrromethane cofactor by the apoenzyme from two molecules of porphobilinogen or from preuroporphyrinogen. The covalently linked cofactor acts as a primer, around which the tetrapyrrole product is assembled. In the last step of catalysis, the product, preuroporphyrinogen, is released, leaving the cofactor bound to the holodeaminase intact.|||Belongs to the HMBS family.|||Binds 1 dipyrromethane group covalently.|||Monomer. http://togogenome.org/gene/10090:Nrm ^@ http://purl.uniprot.org/uniprot/Q8VC65 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the nurim family.|||Nucleus inner membrane http://togogenome.org/gene/10090:Prodh2 ^@ http://purl.uniprot.org/uniprot/Q8VCZ9 ^@ Developmental Stage|||Function|||Induction|||Similarity ^@ Belongs to the proline oxidase family.|||Dehydrogenase that converts trans-4-L-hydroxyproline to delta-1-pyrroline-3-hydroxy-5-carboxylate (Hyp) using ubiquinone-10 as the terminal electron acceptor. Can also use proline as a substrate but with a very much lower efficiency. Does not react with other diastereomers of Hyp: trans-4-D-hydroxyproline and cis-4-L-hydroxyproline. Ubiquininone analogs such as menadione, duroquinone and ubiquinone-1 react more efficiently than oxygen as the terminal electron acceptor during catalysis.|||Expressed in liver at 14 dpc. Expression level increases at P5 and decreases after P21.|||In liver, by TCF1 and HNF4A. http://togogenome.org/gene/10090:Gm6121 ^@ http://purl.uniprot.org/uniprot/L7MUF1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Kif5c ^@ http://purl.uniprot.org/uniprot/P28738 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin subfamily.|||Chimeric cDNA. The C-terminus (up to position 300) corresponds to KIF5C sequence.|||Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.|||Microtubule-associated force-producing protein that may play a role in organelle transport. Has ATPase activity (By similarity). Involved in synaptic transmission (By similarity). Mediates dendritic trafficking of mRNAs (PubMed:19608740). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity).|||Oligomer composed of two heavy chains and two light chains (PubMed:15286375). Interacts with GRIP1 (PubMed:11986669). Interacts with KLC3 and TRAK1 (By similarity). Interacts with ZFYVE27 (PubMed:21976701).|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Mei1 ^@ http://purl.uniprot.org/uniprot/Q9D4I2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Tissue Specificity ^@ Highly expressed in 17 dpc ovaries. Expression is significantly reduced in newborn ovaries, and is undetectable in ovaries from 5 day and 8 week old mice.|||Mice are infertile due to meiotic arrest caused by defects in chromosome synapsis. They lack zygotene Rad51 foci, and are likely to be deficient in meiotic double-strand break (DSB) formation. In addition, mutant spermatocytes exhibit meiotic arrest at entry into pachynema, whereas oocytes progress to an abnormal metaphase I. MEI1-deficient oocytes are capable of fertilization. The zygotes are capable of initiating embryonic development but mostly arrest at the 2-4 cell stage. Among all the zygotes, approximately 5% are androgenetic and do not contain maternal chromosomes (PubMed:30388401).|||Required for normal meiotic chromosome synapsis. May be involved in the formation of meiotic double-strand breaks (DSBs) in spermatocytes.|||Strongly expressed in testis, weakly in brain, and not detected in spleen, liver, kidney, small intestine or colon. http://togogenome.org/gene/10090:ATP6 ^@ http://purl.uniprot.org/uniprot/P00848|||http://purl.uniprot.org/uniprot/Q7JCY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase A chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). Interacts with DNAJC30; interaction is direct (By similarity).|||Membrane|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pdss2 ^@ http://purl.uniprot.org/uniprot/Q33DR3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FPP/GGPP synthase family.|||Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1 subunits.|||Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination of the side chain of ubiquinone (PubMed:16262699). Supplies nona and decaprenyl diphosphate, the precursors for the side chain of the isoprenoid quinones ubiquinone-9 (Q9) and ubiquinone-10 (Q10) respectively (PubMed:16262699). The enzyme adds isopentenyl diphosphate molecules sequentially to farnesyl diphosphate with trans stereochemistry (PubMed:16262699). May play a role during cerebellar development (PubMed:21871565). May regulate mitochondrial respiratory chain function (PubMed:18437205).|||Homozygous mice for PDSS2 are embryonic lethal (PubMed:18437205, PubMed:21871565). The oldest PDSS2 embryo identified is at E9.5, and its morphology resembles normal E6.5 mouse embryo, so the development of mutant embryo may be blocked at late gastrula stage (PubMed:18437205, PubMed:21871565). Conditional knockout mice lacking PDSS2 in cerebellum show severe cerebellum hypoplasia during cerebellum development, whereas conditional knockout mice lacking PDSS2 in Purkinje cells at postnatal stages leads to the development of cerebellar ataxia (PubMed:21871565). Conditional knockout mice lacking PDSS2 in glomeruli show interstitial nephritis characterized by greatly dilated tubules and extensive interstitial infiltration associated with hypercholesterolemia (PubMed:18437205). Liver-conditional knockout mice have no overt disease but their livers have undetectable COQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism (PubMed:18437205).|||Mitochondrion http://togogenome.org/gene/10090:Wdpcp ^@ http://purl.uniprot.org/uniprot/B1ATJ7|||http://purl.uniprot.org/uniprot/Q8C456 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat fritz family.|||Cell membrane|||Interacts with CPLANE1. Interacts with INTU and FUZ; FUZ, INTU and WDPCP probably form the core CPLANE (ciliogenesis and planar polarity effectors) complex.|||Membrane|||Probable effector of the planar cell polarity signaling pathway which regulates the septin cytoskeleton in both ciliogenesis and collective cell movements. Together with FUZ and WDPCP proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (PubMed:27158779).|||Y-shaped metacarpals and defects in palate and tongue morphology characteristic for a PFD syndrome phenotype.|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Slc15a5 ^@ http://purl.uniprot.org/uniprot/Q8CBB2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.|||Membrane|||Proton oligopeptide cotransporter. http://togogenome.org/gene/10090:Tcof1 ^@ http://purl.uniprot.org/uniprot/O08784 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expression elevated at 11 dpc when the branchial arches and facial swellings are present.|||Heterodimer; heterodimerizes with NOLC1 following monoubiquitination. Part of a large pre-ribosomal ribonucleoprotein (RNP) complex, that consists of at least 62 ribosomal proteins, 45 nonribosomal proteins and both pre-rRNA and mature rRNA species. Within this complex directly interacts with NOP56 in an RNA-independent manner.|||Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification. Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification.|||Pyrophosphorylated by 5-diphosphoinositol pentakisphosphate (5-IP7) (PubMed:17873058). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue (PubMed:17873058).|||Ubiquitinated. Monoubiquitination by the BCR(KBTBD8) complex promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification.|||Ubiquitous in adult and embryonic tissues.|||nucleolus http://togogenome.org/gene/10090:Col20a1 ^@ http://purl.uniprot.org/uniprot/Q923P0 ^@ Function|||Subcellular Location Annotation ^@ Probable collagen protein.|||extracellular space http://togogenome.org/gene/10090:Wdr3 ^@ http://purl.uniprot.org/uniprot/Q8BHB4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat WDR3/UTP12 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Or5ae2 ^@ http://purl.uniprot.org/uniprot/Q8VF60 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp6v1f ^@ http://purl.uniprot.org/uniprot/Q9D1K2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase F subunit family.|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity).|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Icos ^@ http://purl.uniprot.org/uniprot/Q3V3X2|||http://purl.uniprot.org/uniprot/Q5SUZ7|||http://purl.uniprot.org/uniprot/Q9WVS0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes (By similarity).|||Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes.|||Expressed on activated T-cells and resting memory T-cells. High expression seen in the thymic medulla and in the germinal centers and T-cell zones of lymph nodes and Peyer patches. Expressed at low levels in the spleen.|||Homodimer; disulfide-linked.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Abca8a ^@ http://purl.uniprot.org/uniprot/A4PBQ7|||http://purl.uniprot.org/uniprot/F8WGE3|||http://purl.uniprot.org/uniprot/Q8K442 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the ABC transporter superfamily. ABCA family.|||Cell membrane|||Cholesterol efflux is increased by extracellularly applied taurocholate.|||Down-regulated by digoxin.|||Expressed in lung, heart, liver, skeletal muscle and testis (PubMed:12532264, PubMed:16445568). Highly expressed in the liver, and is also abundant in heart and skeletal muscle (PubMed:28882873). Highly expressed in heart (PubMed:29300488).|||Expression is first detected at 17 dpc.|||Mediates cholesterol and taurocholate efflux. Through the interaction with ABCA1 potentiates the cholesterol efflux to lipid-free APOA1, in turn regulates high-density lipoprotein cholesterol levels.|||Membrane http://togogenome.org/gene/10090:Ern1 ^@ http://purl.uniprot.org/uniprot/Q9EQY0 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by PARP16 upon ER stress, which increases both kinase and endonuclease activities.|||Autophosphorylated following homodimerization. Autophosphorylation promotes activation of the endoribonuclease domain (PubMed:25164867). In response to ER stress, phosphorylated at Ser-724, Ser-729 and possibly Ser-726; phosphorylation promotes oligomerization and endoribonuclease activity (PubMed:30118681). Dephosphorylated at Ser-724, Ser-729 and possibly Ser-726 by RPAP2 to abort failed ER-stress adaptation and trigger apoptosis (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Endoplasmic reticulum membrane|||Expressed in liver (at protein level) (PubMed:30118681). Ubiquitously expressed (PubMed:11146108). High levels in thymus, liver and lung. In the brain, preferentially expressed in cortical, hippocampal and olfactory neurons (PubMed:11146108).|||Monomer (By similarity). Homodimer; disulfide-linked; homodimerization takes place in response to endoplasmic reticulum stress and promotes activation of the kinase and endoribonuclease activities (PubMed:25164867). Dimer formation is driven by hydrophobic interactions within the N-terminal luminal domains and stabilized by disulfide bridges (PubMed:25164867). Interacts (via the luminal region) with DNAJB9/ERdj4; interaction takes place in unstressed cells and promotes recruitment of HSPA5/BiP (By similarity). Interacts (via the luminal region) with HSPA5/BiP; HSPA5/BiP is a negative regulator of the unfolded protein response (UPR) that prevents homodimerization of ERN1/IRE1 and subsequent activation of the protein (By similarity). Interacts with PDIA6, a negative regulator of the UPR; the interaction is direct and disrupts homodimerization (By similarity). Interacts with DAB2IP (via PH domain); the interaction occurs in a endoplasmic reticulum stress-induced dependent manner and is required for subsequent recruitment of TRAF2 to ERN1/IRE1 (PubMed:18281285). Interacts with TAOK3 and TRAF2 (By similarity). Interacts with RNF13 (By similarity). Interacts with LACC1 (By similarity). Interacts (when unphosphorylated) with DDRGK1; interaction is dependent on UFM1 and takes place in response to endoplasmic reticulum stress, regulating ERN1/IRE1-alpha stability (By similarity). Interacts (via N-terminus) with P4HB/PDIA1; the interaction is enhanced by phosphorylation of P4HB by FAM20C in response to endoplasmic reticulum stress and results in attenuation of ERN1 activity (By similarity).|||Serine/threonine-protein kinase and endoribonuclease that acts as a key sensor for the endoplasmic reticulum unfolded protein response (UPR) (PubMed:11850408, PubMed:25164867). In unstressed cells, the endoplasmic reticulum luminal domain is maintained in its inactive monomeric state by binding to the endoplasmic reticulum chaperone HSPA5/BiP. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP, allowing the luminal domain to homodimerize, promoting autophosphorylation of the kinase domain and subsequent activation of the endoribonuclease activity (PubMed:25164867). The endoribonuclease activity is specific for XBP1 mRNA and excises 26 nucleotides from XBP1 mRNA (PubMed:11850408, PubMed:25164867). The resulting spliced transcript of XBP1 encodes a transcriptional activator protein that up-regulates expression of UPR target genes (PubMed:11850408, PubMed:25164867). Acts as an upstream signal for ER stress-induced GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane by modulating the expression and localization of SEC16A (By similarity).|||The kinase domain is activated by trans-autophosphorylation following homodimerization. Kinase activity is required for activation of the endoribonuclease domain (PubMed:25164867). Endoribonuclease activity is specifically inhibited by hydroxy-aryl-aldehydes (HAA) MKC9989, OICR464 and OICR573 (PubMed:25164867). http://togogenome.org/gene/10090:Slc27a1 ^@ http://purl.uniprot.org/uniprot/Q544D7|||http://purl.uniprot.org/uniprot/Q60714 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Cell membrane|||Cytoplasm|||Endomembrane system|||Expression is down-regulated by insulin.|||Higher expression in differentiated adipocytes compared to preadipocytes.|||Higher expression in white adipose tissue than in heart (PubMed:12556534). Highest expression in skeletal muscle, heart and fat. Lower levels in brain, kidney, lung, liver and testis. No expression in spleen or intestine.|||Inhibited by Triacsin C (PubMed:12235169). Both insulin and muscle contraction stimulate translocation to the plasma membrane in muscle, increasing fatty acid transport activity (PubMed:19527715).|||Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane (PubMed:7954810, PubMed:9786857, PubMed:9671728, PubMed:10471110, PubMed:12235169, PubMed:11970897, PubMed:15699031, PubMed:28178239, PubMed:24858472, PubMed:19527715) (Probable). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (PubMed:10593920, PubMed:12235169, PubMed:12937175). May act directly as a bona fide transporter, or alternatively, in a cytoplasmic or membrane-associated multimeric protein complex to trap and draw fatty acids towards accumulation (PubMed:14991074, PubMed:15897321). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis (PubMed:12235169). May be involved in regulation of cholesterol metabolism (PubMed:12235169). Probably involved in fatty acid transport across the blood barrier (By similarity).|||Mice deficient for Slc27a1 are viable and do not display overt developmental phenotype or alteration in whole-body adiposity. However, they are protected from fat-induced accumulation of intramuscular fatty acyl-CoA and insulin resistance in skeletal muscle.|||Mitochondrion outer membrane|||Self-associates. May function as a homodimer (PubMed:12533547). Interacts with EPRS1; mediates the translocation of SLC27A1 from the cytoplasm to the plasma membrane thereby increasing the uptake of long-chain fatty acids (PubMed:28178239). Interacts with DGAT2 and this interaction is enhanced in the presence of ZFYVE1 (By similarity). http://togogenome.org/gene/10090:Xpo4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J254|||http://purl.uniprot.org/uniprot/Q9ESJ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the exportin family.|||Cytoplasm|||Interacts with Ran and cargo proteins in a GTP-dependent manner.|||Mediates the nuclear export of proteins (cargos), such as EIF5A, SMAD3 and isoform M2 of PKM (PKM2) (By similarity). In the nucleus binds cooperatively to its cargo and to the GTPase Ran in its active GTP-bound form (By similarity). Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins (By similarity). Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor (By similarity). XPO4 then return to the nuclear compartment and mediate another round of transport (By similarity). The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Catalyzes the nuclear export of hypusinated EIF5A; a small cytoplasmic protein that enters nucleus and accumulates within nucleolus if not exported back by XPO4 (PubMed:27306458). Specifically mediates nuclear export of isoform M2 of PKM (PKM2) following PKM2 deacetylation by SIRT6 (By similarity). Also mediates the nuclear import of SOX transcription factors SRY and SOX2 (PubMed:19349578).|||Nucleus http://togogenome.org/gene/10090:Ednrb ^@ http://purl.uniprot.org/uniprot/P48302 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Endothelin receptor subfamily. EDNRB sub-subfamily.|||Cell membrane|||Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Essential component in the normal development of two neuronal crest-derived cell lineages. http://togogenome.org/gene/10090:Rep15 ^@ http://purl.uniprot.org/uniprot/Q9D7T1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Early endosome membrane|||Interacts with the GTP-bound form of RAB15.|||Regulates transferrin receptor recycling from the endocytic recycling compartment. http://togogenome.org/gene/10090:Stard6 ^@ http://purl.uniprot.org/uniprot/P59096|||http://purl.uniprot.org/uniprot/Q8C1R6|||http://purl.uniprot.org/uniprot/Q9CPT8 ^@ Function|||Tissue Specificity ^@ May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols (By similarity).|||May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.|||Testis. http://togogenome.org/gene/10090:Clstn3 ^@ http://purl.uniprot.org/uniprot/D3Z601|||http://purl.uniprot.org/uniprot/Q99JH7 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adipose-specific isoform that plays a key role in adaptive thermogenesis (PubMed:31043739, PubMed:36477540). Facilitates the efficient use of stored triglyceride by promoting multilocular morphology of thermogenic adipocytes: acts by inhibiting the activity of CIDEA and CIDEC on lipid droplets, thereby preventing lipid droplet fusion and facilitating lipid utilization (PubMed:36477540). May also participate in adaptive thermogenesis by promoting sympathetic innervation of thermogenic adipose tissue: acts by driving secretion of neurotrophic factor S100B from brown adipocytes, stimulating neurite outgrowth from sympathetic neurons (PubMed:31043739).|||Belongs to the calsyntenin family.|||Endoplasmic reticulum membrane|||Expression is induced by cold and PPAR-gamma (PPARG).|||Expression is restricted to adipose tissue, with high expression in thermogenic adipocytes (brown adipose tissue).|||Golgi apparatus membrane|||Interacts (via cadherin domains) with both alpha and beta isoforms of neurexins (NRXN1, NRXN2 and NRXN3) (PubMed:24094106, PubMed:24613359, PubMed:32434929). Directly interacts with APBA2 (By similarity). Forms a tripartite complex with APBA2 and APP (By similarity). Interacts with low affinity with KLC1 (PubMed:16760430). Interacts with SLC23A2/SVCT2 (By similarity).|||Interacts with CIDEA; inhibiting the lipid transferase activity of CIDEA (PubMed:36477540). Interacts with CIDEC; inhibiting the lipid transferase activity of CIDEC (PubMed:36477540).|||Lipid droplet|||Mice are defective in both excitatory and inhibitory synapse development (PubMed:24094106). Mice also show reduced body mass and increased energy expenditure (PubMed:32382066). Mice also display reduced marrow volume and cortical bone mass without alteration of trabecular bone microarchitecture (PubMed:32382066). Conditional deletion in neurons leads to a significant reduction in number of excitatory synaptic inputs (PubMed:32434929). Conditional deletion in the cerebellum causes major impairments in motor learning due to a large decrease in inhibitory synapse, associated with a robust increase in excitatory parallel-fiber synapses in Purkinje cells (PubMed:35420982). As a result, inhibitory synaptic transmission is suppressed, whereas parallel-fiber synaptic transmission is enhanced in Purkinje cells (PubMed:35420982). No changes in the dendritic architecture of Purkinje cells or in climbing-fiber synapses is observed (PubMed:35420982). Mice lacking Clstn1, Clstn2 and Clstn3 display behavior disorders, characterized by hyperactivity in normal environment, hypersensitivity to stress, and show tendency to freeze in novel environments (PubMed:35279170).|||Mice are defective in energy expenditure and adaptive thermogenesis: mutant mice are hypothermic at a faster rate than controls during acute cold challenge (PubMed:31043739, PubMed:36477540). Mice show larger and paler brown adipose tissue and display abnormal lipid droplet forms (PubMed:36477540).|||Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation (PubMed:24094106, PubMed:24613359, PubMed:32434929, PubMed:35420982). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with both neurexin-alpha and neurexin-beta proteins at the presynaptic membrane (PubMed:24094106, PubMed:24613359, PubMed:32434929). Regulates the balance between excitatory and inhibitory synapses by inhibiting formation of excitatory parallel-fiber synapses and promoting formation of inhibitory synapses in the same neuron (PubMed:35420982). May also be involved in ascorbate (vitamin C) uptake via its interaction with SLC23A2/SVCT2 (PubMed:33672967). Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation (By similarity).|||Postsynaptic cell membrane|||Proteolytically processed under normal cellular conditions. A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1). A secondary cleavage catalyzed by gamma-secretase within the transmembrane domain releases the beta-Alc-beta chain in the extracellular milieu and produces an intracellular fragment (AlcICD). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with gamma-secretase.|||Restricted to the brain (at protein level) (PubMed:12498782, PubMed:24094106). In the cerebral cortex, found in the somas and neuropil of all layers (PubMed:12498782). Expressed at highest levels in neurons of cortical layer 5 and, at lower levels, in neurons of the upper layers (PubMed:12498782). Highly expressed in Purkinje cells (PubMed:12498782). Also found in a few scattered interneurons throughout the granule cell layer and occasionally in neurons in the molecular layer (at protein level) (PubMed:12498782). In all layers, high levels in a subpopulation of presumptive GABAergic neurons (based on morphology) (PubMed:12498782).|||The cytoplasmic domain binds synaptic Ca(2+).|||Ubiquitinated: endoplasmic reticulum-localized protein is ubiquitinated and degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway.|||dendrite http://togogenome.org/gene/10090:Coq5 ^@ http://purl.uniprot.org/uniprot/Q9CXI0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. MenG/UbiE family.|||Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with PYURF; the interaction is direct, stabilizes COQ5 protein and associates PYURF with COQ enzyme complex (By similarity).|||Methyltransferase required for the conversion of 2-polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gosr1 ^@ http://purl.uniprot.org/uniprot/O88630 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GOSR1 family.|||Component of several multiprotein Golgi SNARE complexes. Identified in a SNARE complex with BET1, STX5 and YKT6, in a SNARE complex with BET1L, STX5 and YKT6, in a SNARE complex with STX5, GOSR2, SEC22B and BET1, and in complex with STX5 and COG3. Interacts with GABARAPL2 (By similarity).|||Decreased levels in 25-hydroxycholesterol treated melanocytes (at protein level).|||Golgi apparatus membrane|||Involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. It belongs to a super-family of proteins called t-SNAREs or soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor. May play a protective role against hydrogen peroxide induced cytotoxicity under glutathione depleted conditions in neuronal cells by regulating the intracellular ROS levels via inhibition of p38 MAPK (MAPK11, MAPK12, MAPK13 and MAPK14). Participates in docking and fusion stage of ER to cis-Golgi transport. Plays an important physiological role in VLDL-transport vesicle-Golgi fusion and thus in VLDL delivery to the hepatic cis-Golgi (By similarity). http://togogenome.org/gene/10090:Sash1 ^@ http://purl.uniprot.org/uniprot/P59808 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in the microvascular endothelium of various organs, as well as in parenchymal cells. Expressed in the endothelium but not lymphoid cells of spleen and thymus.|||Interacts with GNAS. Interacts with IQGAP1. Interacts with TRAF6 (via C-terminus); the interaction is LPS-dependent. Interacts with MAP3K7, CHUK and IKBKB.|||Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation. Regulates TRAF6 and MAP3K7 ubiquitination. Involved in the regulation of cell mobility. Regulates lipolysaccharide (LPS)-induced endothelial cell migration. Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis. http://togogenome.org/gene/10090:Cntnap1 ^@ http://purl.uniprot.org/uniprot/O54991 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neurexin family.|||Expressed in brain. In myelinated nerve fibers predominantly found in paranodal axoglial junctions. In the internodal region of myelinated axons in the CNS and the PNS also found as a thin line apposing the inner mesaxon of the myelin sheath. In PNS neurons this line forms a circumferential ring that apposes the innermost aspect of Schmidt-Lanterman incisures.|||Interacts with CNTN1/contactin in cis form.|||Membrane|||Mutant mice exhibit tremor, ataxia, and significant motor paresis. Normal paranodal junctions fail to form, and the organization of the paranodal loops is disrupted. Contactin is undetectable in the paranodes, and potassium channels are displaced from the juxtaparanodal into the paranodal domains. Also results in a severe decrease in peripheral nerve conduction velocity (PubMed:11395000, PubMed:25378149). Double mutants CNTNAP1 and CNTNAP2 have wider Ranvier nodes compared to wild-type littermates (PubMed:25378149).|||Required, with CNTNAP2, for radial and longitudinal organization of myelinated axons (PubMed:25378149). Plays a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Demarcates the paranodal region of the axo-glial junction. In association with contactin involved in the signaling between axons and myelinating glial cells (PubMed:25378149, PubMed:11395000).|||paranodal septate junction http://togogenome.org/gene/10090:Hectd2 ^@ http://purl.uniprot.org/uniprot/Q8CDU6 ^@ Function ^@ E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. http://togogenome.org/gene/10090:Enho ^@ http://purl.uniprot.org/uniprot/Q8K1D8 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in liver and brain. Expressed in regions of the brain involved in metabolic regulation.|||In liver, up-regulated in mice fed a high-fat diet for 2 days, and down-regulated in obese mice fed a chronic high fat diet. Also down-regulated in liver 4 hours after treatment with LXR agonist GW3965.|||Involved in the regulation of glucose homeostasis and lipid metabolism.|||Secreted http://togogenome.org/gene/10090:Acp4 ^@ http://purl.uniprot.org/uniprot/D3YTS9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histidine acid phosphatase family.|||Glycosylated.|||Homodimer.|||In the developing tooth from 8-day-old mice it is expressed in secretory-stage ameloblasts, follicular cells, odontoblasts, and osteoblasts (at protein level).|||May dephosphorylate receptor tyrosine-protein kinase ERBB4 and inhibits its ligand-induced proteolytic cleavage. May play a role in odontogenesis.|||Membrane http://togogenome.org/gene/10090:Sacm1l ^@ http://purl.uniprot.org/uniprot/Q9EP69 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in brain, lung, liver and kidney, and at lower levels in spleen and skeletal muscle.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with TMEM39A (By similarity). Interacts with SEC23A and SEC24A; this interaction is reduced in the absence of TMEM39A (By similarity). Interacts with PLEKHA3 and VAPA and/or VAPB to form a ternary complex (By similarity).|||Phosphoinositide phosphatase which catalyzes the hydrolysis of phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 3-phosphate (PtdIns(3)P) and has low activity towards phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2) (By similarity). Shows a very robust PtdIns(4)P phosphatase activity when it binds PtdIns(4)P in a 'cis' configuration in the cellular environment, with much less activity seen when it binds PtdIns(4)P in 'trans' configuration (By similarity). PtdIns(4)P phosphatase activity (when it binds PtdIns(4)P in 'trans' configuration) is enhanced in the presence of PLEKHA3 (By similarity). http://togogenome.org/gene/10090:Galr2 ^@ http://purl.uniprot.org/uniprot/O88854|||http://purl.uniprot.org/uniprot/Q8BKB0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for the hormone galanin, GALP and spexin-1. The activity of this receptor is mediated by G proteins that activate the phospholipase C/protein kinase C pathway (via G(q)) and that inhibit adenylyl cyclase (via G(i)). http://togogenome.org/gene/10090:Ces1c ^@ http://purl.uniprot.org/uniprot/P23953 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Endoplasmic reticulum lumen|||Expressed in lung, kidney and liver.|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Involved in the extracellular metabolism of lung surfactant.|||Sequencing errors. http://togogenome.org/gene/10090:Vit ^@ http://purl.uniprot.org/uniprot/Q8VHI5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ At 16.5 dpc, present in skull base cartilage (at protein level) (PubMed:18757743). Expressed in the floor plate as early as 9.5 dpc and shifted to the central canal area from 13.5 dpc. At 15.5 dpc, the expression is restricted to the ventral midline region (PubMed:25331329).|||Binds dermatan sulfate and chondroitin sulfate.|||Embryos show decreased spinal cord size associated with reduced cell proliferation and altered cell differentiation in the central canal of the neural tube.|||Highly up-regulated in the injured spinal cord.|||Promotes matrix assembly and cell adhesiveness (PubMed:18757743). Plays a role in spinal cord formation by regulating the proliferation and differentiation of neural stem cells (PubMed:25331329).|||extracellular matrix http://togogenome.org/gene/10090:Dio1 ^@ http://purl.uniprot.org/uniprot/Q61153 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the iodothyronine deiodinase family.|||Endoplasmic reticulum membrane|||Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2 (3,3'-diiodothyronine). http://togogenome.org/gene/10090:Or4c122 ^@ http://purl.uniprot.org/uniprot/Q8VGM9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mthfsl ^@ http://purl.uniprot.org/uniprot/L7N466 ^@ Similarity ^@ Belongs to the 5-formyltetrahydrofolate cyclo-ligase family. http://togogenome.org/gene/10090:Zmiz1 ^@ http://purl.uniprot.org/uniprot/Q6P1E1 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as transcriptional coactivator. Increases ligand-dependent transcriptional activity of AR and promotes AR sumoylation. The stimulation of AR activity is dependent upon sumoylation (By similarity). Also functions as a transcriptional coactivator in the TGF-beta signaling pathway by increasing the activity of the SMAD3/SMAD4 transcriptional complex (By similarity). Involved in transcriptional activation of a subset of NOTCH1 target genes including MYC. Involved in thymocyte and T cell development (PubMed:26522984). Involved in the regulation of postmitotic positioning of pyramidal neurons in the developing cerebral cortex (By similarity).|||Cytoplasm|||Death between 9.5-10.5 dpc. Mice are approximately half the size of wild-type littermates and display vascular and cell viability defects. Some heterozygotes also do not survive but those that do have no apparent defects.|||Expressed in brain.|||Interacts with AR, but not with ESR1, NR3C1, PGR, THRB nor VDR. Interacts with NOTCH1 and RBPJ (By similarity). Interacts with SMARCA4. Interacts (via SP-RING-type domain) with SMAD3 and SMAD4 (via MH2 domain) (By similarity).|||Intron retention.|||May be due to a competing acceptor splice site.|||The C-terminal proline-rich domain possesses a significant intrinsic transcriptional activity. This activity is inhibited by the N-terminus in the full-length protein.|||The SP-RING-type domain mediates interaction with SMAD3 and SMAD4.|||nucleoplasm http://togogenome.org/gene/10090:Or5p79 ^@ http://purl.uniprot.org/uniprot/Q8VG13 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Dgat1 ^@ http://purl.uniprot.org/uniprot/Q54AA6|||http://purl.uniprot.org/uniprot/Q9Z2A7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.|||Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates (PubMed:15834126, PubMed:19028692, PubMed:20876538, PubMed:22493088, PubMed:28420705). Highly expressed in epithelial cells of the small intestine and its activity is essential for the absorption of dietary fats (By similarity). In liver, plays a role in esterifying exogenous fatty acids to glycerol, and is required to synthesize fat for storage (PubMed:15834126). Also present in female mammary glands, where it produces fat in the milk (By similarity). May be involved in VLDL (very low density lipoprotein) assembly (By similarity). In contrast to DGAT2 it is not essential for survival (PubMed:11959864). Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders (PubMed:19028692). Exhibits additional acyltransferase activities, includin acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases (PubMed:15834126). Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705).|||Endoplasmic reticulum membrane|||Homodimer or homotetramer; both forms have similar enzymatic activities.|||Membrane|||Mice are viable and live well, but show substantially reduced levels of triacylglycerides in all tissues (PubMed:10802663, PubMed:11959864, PubMed:11956242). Mice are resistant to obesity when kept on a high-fat diet due to increased energy expenditure: they display reduced postabsorptive chylomicronemia and accumulate neutral-lipid droplets in the cytoplasm of enterocytes (PubMed:10802663, PubMed:11959864, PubMed:11956242). Mice also show increased sensitivity to insulin and to leptin and are protected against insulin resistance (PubMed:11956242). Mutant mice show reduced levels of monoalkyl-monoacylglycerol (MADAG) in the adrenal gland (PubMed:28420705).|||The MBOAT fold forms a reaction chamber in the endoplasmic reticulum membrane that encloses the active sites. The reaction chamber has a tunnel to the cytosolic side and its entrance recognizes the hydrophilic CoA motif of an acyl-CoA molecule. The chamber has separate entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-glycerol.|||The disordered N-terminal region is required for the diacylglycerol O-acyltransferase activity and may regulate enzymatic function via its interaction with the MBOAT fold. http://togogenome.org/gene/10090:Vps26a ^@ http://purl.uniprot.org/uniprot/P40336 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3.The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC complex seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (By similarity). Required for retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:15078902). Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for the endosomal localization of WASHC2 (indicative for the WASH complex). Required for the endosomal localization of TBC1D5. Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (By similarity). Involved in retromer-independent lysosomal sorting of F2R. Involved in recycling of ADRB2 (By similarity). Acts redundantly with VSP26B in SNX-27 mediated endocytic recycling of SLC2A1/GLUT1. Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (PubMed:25136126).|||Belongs to the VPS26 family.|||Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:18088321, PubMed:20875039). The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (Probable). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (By similarity). Interacts with VPS29, VPS35, SNX27 (PubMed:18088321, PubMed:20875039, PubMed:25136126). Interacts with SNX1, SNX2, SNX5, SNX6, SNX3, RAB7A, ECPAS, EHD1, WASHC5, SORL1 (By similarity).|||Cytoplasm|||Early endosome|||Endosome membrane http://togogenome.org/gene/10090:Pias4 ^@ http://purl.uniprot.org/uniprot/Q3ULQ6|||http://purl.uniprot.org/uniprot/Q9JM05 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts ewith Moloney murine leukemia virus Capsid protein p30.|||At 8.5 dpc, expressed primarily in the anterior part of the neural tube. At 10.5 dpc, expressed in the neuroepithelium of the forebrain and hindbrain. At 11.5 dpc, detected in the neural tube, eye, limb buds and brachial arches. At 12.5 dpc, expressed in the hindlimbs and forelimbs, as well as in the forebrain. At 12.5 and 13.5 dpc, detected in single cells in the marginal zone of the developing cortex, as well as in other developing tissues and organs. At 13.5 dpc, expressed in the developing limb buds, in single cells in the mesenchyme surrounding future digit structures. At 15.5 dpc, detected in the inner root sheath of vibrissa hair follicle. Expression in the inner root sheath of the hair follicle continues later in life as it can also be detected in the back skin of newborn at postnatal day 3. At 16.5 dpc, expressed in the epithelium of olfactory and in the retina.|||Belongs to the PIAS family.|||Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (By similarity). Binds to AT-rich DNA sequences, known as matrix or scaffold attachment regions (MARs/SARs) (PubMed:11731474). Catalyzes conjugation of SUMO2 to KAT5 in response to DNA damage, facilitating repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity). Mediates sumoylation of PARP1 in response to PARP1 trapping to chromatin (By similarity).|||Interacts with AR, AXIN1, GATA2, TP53 and STAT1 (IFNG-induced) (By similarity). Interacts with LEF1 (PubMed:11731474). Interacts with TICAM1 (By similarity). Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase (By similarity). Interacts with MTA1 (By similarity). Interacts with PRDM1/Blimp-1 (By similarity). Interacts with TRIM32 upon treatment with UVB and TNF-alpha (PubMed:16816390).|||PML body|||Sumoylated. Lys-35 is the main site of sumoylation. Sumoylation is required for TCF4 sumoylation and transcriptional activation. Represses LEF1 transcriptional activity. SUMO1 is the preferred conjugate.|||The LXXLL motif is a coregulator signature that is essential for transcriptional corepression.|||Ubiquitinated by TRIM32 upon treatment with UVB and TNF-alpha.|||Widely expressed, with highest levels in testis. Also expressed in vascular endothelial cells, in primary keratinocytes and in the CNS, including cortex, olfactory bulb, spinal cord, thalamus and trigeminal ganglion. Low expression, if any, in liver and lung. http://togogenome.org/gene/10090:Fam47e ^@ http://purl.uniprot.org/uniprot/B2RVF4|||http://purl.uniprot.org/uniprot/E9PYM1|||http://purl.uniprot.org/uniprot/E9Q0Z5|||http://purl.uniprot.org/uniprot/Q3UN37 ^@ Similarity ^@ Belongs to the FAM47 family. http://togogenome.org/gene/10090:Or10d1b ^@ http://purl.uniprot.org/uniprot/Q60888 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Tppp3 ^@ http://purl.uniprot.org/uniprot/Q9CRB6 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPPP family.|||Cytoplasm|||Expressed in the connective tissues of differentiating tendons and synovial joints (PubMed:19235716). Expressed in the uterus during window of implantation and early pregnancy (at protein level) (PubMed:29901777).|||Regulator of microtubule dynamic that has microtubule bundling activity (By similarity). Required for embryo implantation; possibly by regulating beta-catenin (PubMed:29901777). Also required for decidualization via regulation of beta-catenin (PubMed:30667362).|||Up-regulated by estradiol.|||cytoskeleton http://togogenome.org/gene/10090:Srpk1 ^@ http://purl.uniprot.org/uniprot/O70551|||http://purl.uniprot.org/uniprot/Q3URR1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Ser-51 and Ser-548.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.|||Chromosome|||Cytoplasm|||Microsome|||Monomer. Found in a multisubunit complex containing seven proteins, named toposome, which separates entangled circular chromatin DNA during chromosome segregation. Interacts with HHV-1 ICP27 protein. Interacts with DNAJC8 and AHSA1/AHA1 and this mediates formation of a complex with the Hsp70 /Hsp90 machinery. Binds to IGF2BP1, SYNCRIP, HNRNPA2B1 and HNRNPC. Interacts with SAFB/SAFB1 and SAFB2 which inhibits its activity (By similarity).|||Nucleus matrix|||Nucleus speckle|||Predominantly expressed in the testis but is also present at lower levels in heart, spleen, liver, brain, kidney, lung and skeletal muscle. Present in all germinal cells in the seminiferous tubules but not in mature spermatozoa.|||Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Phosphorylates SFRS2, ZRSR2, LBR and PRM1. Phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Can induce splicing of exon 10 in MAPT/TAU (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Snrpc ^@ http://purl.uniprot.org/uniprot/Q569X3|||http://purl.uniprot.org/uniprot/Q62241 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the U1 small nuclear ribonucleoprotein C family.|||Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. SNRPC/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA (By similarity). Interacts (via N-terminus) with TIA1 (via C-terminus); thereby promoting spliceosomal U1 snRNP recruitment to 5' splice sites (By similarity).|||Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. SNRPC/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.|||Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. snrpc/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates E complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.|||First detected in the testis 18 days after birth. Levels increase successively between days 21-28. On day 42, levels decrease.|||Nucleus|||U1 snRNP is composed of the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. SNRPC/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.|||Widely expressed. In the testis, expressed in somatic and germinal testicular cells but not in elongated spermatids. http://togogenome.org/gene/10090:Cog5 ^@ http://purl.uniprot.org/uniprot/Q8C0L8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG5 family.|||Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.|||Golgi apparatus membrane|||Required for normal Golgi function.|||cytosol http://togogenome.org/gene/10090:Ggnbp2 ^@ http://purl.uniprot.org/uniprot/Q5SV77 ^@ Developmental Stage|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed during spermatogenesis. Not detected in newborn animals, in which spermatogenesis has not yet progressed beyond the earliest stages.|||By dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin).|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasmic vesicle|||Interacts with isoform 1 of GGN.|||May be involved in spermatogenesis.|||Testis-specific. http://togogenome.org/gene/10090:Fap ^@ http://purl.uniprot.org/uniprot/P97321 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S9B family.|||Cell membrane|||Cell surface|||Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2. Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vibronectin, tenascin, laminin, fibronectin, fibrin or casein. Also has dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro. Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner.|||Expressed in developing myotubes at 11.5 dpc. Expressed in the dermomyotome component of the somites at 12.5 dpc. Expressed in fibroblasts at 13 dpc. Expressed in the perichondrial mesenchymal cells from the cartilage primordium of the ribs and in the scattered developing intercostal muscle fibs at 16.5 dpc (at protein level). Expressed in the primitive mesenchymal condensation adjacent to the eye and in primitive mesenchymal cells surrounding the cartilaginous primordia of the bones at 13.5 dpc.|||Expressed strongly in uterus, pancreas, submaxillary gland and skin, less in lymph node, ovary, skeletal muscle, adrenal and bone marrow. Expressed in reactive stromal fibroblast in epithelial cancers. Expressed in melanocytes but not melanomas (at protein level). Detected in fibroblasts, in placenta, uterus, embryos from day 7-19 and in newborn mice (P1).|||Gelatinase activity is inhibited by serine-protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF). Dipeptidyl peptidase activity is inhibited by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP). Prolyl endopeptidase activity is inhibited by the boronic acid peptide Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-chloromethyl ketone.|||Homodimer; homodimerization is required for activity of both plasma membrane and soluble forms. The monomer is inactive. Heterodimer with DPP4. Interacts with PLAUR; the interaction occurs at the cell surface of invadopodia membranes. Interacts with ITGB1. Interacts with ITGA3. Associates with integrin alpha-3/beta-1; the association occurs in a collagen-dependent manner at the cell surface of invadopodia membranes.|||Membrane|||N-glycosylated.|||No visible phenotype. Mice are viable and fertile and display no overt developmental defects and no general change in cancer susceptibiliy.|||Secreted|||The N-terminus may be blocked.|||invadopodium membrane|||lamellipodium membrane|||ruffle membrane http://togogenome.org/gene/10090:Myrfl ^@ http://purl.uniprot.org/uniprot/Q3UN70 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MRF family.|||Membrane http://togogenome.org/gene/10090:Zfp354c ^@ http://purl.uniprot.org/uniprot/Q571J5 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in brain. Lower levels in kidney, heart, lung, spleen and eye. Down-regulated during kidney maturation. Expressed in embryonic myogenic progenitor cells, not expressed in adult and aged satellite cells (PubMed:27446912).|||In myogenic progenitor cells, expressed during early myogenic development (11.5 dpc) to be gradually down-regulated during the fetal stages (from 14.5 dpc to adulthood).|||KRAB domain is not required for nuclear targeting or for DNA binding.|||May function as a transcription repressor. Binds to 5'-CCACA-3' core sequence. Suppresses osteogenic effects of RUNX2. May be involved in osteoblastic differentiation (By similarity). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (PubMed:27446912).|||Nucleus|||Zinc finger region is involved in nuclear targeting and DNA-binding. http://togogenome.org/gene/10090:Grxcr2 ^@ http://purl.uniprot.org/uniprot/Q3TYR5 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although it shares high sequence similarity with GRXCR1, it does not contain a canonical glutaredoxin domain.|||Belongs to the GRXCR1 family.|||Could play a role in maintaining cochlear stereocilia bundles that are involved in sound detection.|||Expressed in sensory hair cells in the cochlea and vestibular organ.|||Mice appear normal at postnatal week 2, but develop progressive hearing loss associated with early defects in orientation and organization of cochlear stereocilia bundles. They have normal vestibular function.|||stereocilium http://togogenome.org/gene/10090:Spag4 ^@ http://purl.uniprot.org/uniprot/Q9JJF2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although transmembrane domains are strongly predicted, they may rather represent hydrophobic globular domains associated with microtubules.|||Involved in spermatogenesis. Required for sperm head formation but not required to establish and maintain general polarity of the sperm head. Required for anchoring and organization of the manchette. Required for targeting of SUN3 and probably SYNE1 through a probable SUN1:SYNE3 LINC complex to the nuclear envelope and involved in accurate posterior sperm head localization of the complex. May anchor SUN3 the nuclear envelope. Involved in maintenance of the nuclear envelope integrity. May assist the organization and assembly of outer dense fibers (ODFs), a specific structure of the sperm tail.|||Isoform 1 is testis specific and is exclusively expressed in spermatids.|||Male infertility with severe defects in sperm head formation and globozoospermia-like phenotype.|||Membrane|||Nucleus envelope|||Nucleus inner membrane|||Self-associates. Interacts with ODF1. May associate with microtubules (By similarity). Interacts with SUN3 and SYNE1; suggesting the formation of a spermatogenesis-specific LINC complex; a SUN domain-based heterotrimer of SPAG4 and SUN3 may associate with SYNE1 (PubMed:26621829). Interacts with SEPT12 and LMNB1; during spermatogenesis (By similarity).|||Weakly expressed at day 18 p.p. and increased expression at day 21-25 p.p. with increasing spermatid numbers.|||cytoskeleton|||flagellum axoneme http://togogenome.org/gene/10090:Selenok ^@ http://purl.uniprot.org/uniprot/Q9JLJ1 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the selenoprotein K family.|||By increased dietary selenium. Expression is significantly decreased by a low selenium diet.|||Cell membrane|||Cleaved by CAPN2/m-calpain in resting macrophages but not in activated macrophages. Macrophage activation up-regulates expression of the calpain inhibitor CAST/calpastatin, resulting in inhibition of CAPN2 activity.|||Endoplasmic reticulum membrane|||High expression in spleen and intestine (at protein level). Expressed in a range of immune cells including T and B-cells and also in myeloid cells including macrophages, neutrophils and dendritic cells (at protein level).|||Interacts with DERL1, DERL2, DERL3 and SELENOS (PubMed:22016385). The SELENOK-SELENOS complex interacts with VCP (By similarity). Interacts with ZDHHC6 (PubMed:25368151).|||Normal growth, fertility and immune system development. Reduced receptor-mediated Ca(2+) flux in T-cells, neutrophils and macrophages. Reduced T-cell proliferation and reduced T-cell and neutrophil migration. Decreased viral clearance and increased mortality following infection with West Nile virus. Bone marrow-derived macrophages from knockout mice display decreased uptake of acetylated or oxidized low-density lipoprotein, reduced foam cell formation and decreased palmitoylation and cell surface expression of CD36.|||Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (PubMed:21220695). Involved in endoplasmic reticulum-associated degradation (ERAD) of soluble glycosylated proteins (By similarity). Required for palmitoylation and cell surface expression of CD36 and involved in macrophage uptake of low-density lipoprotein and in foam cell formation (PubMed:23444136). Together with ZDHHC6, required for palmitoylation of ITPR1 in immune cells, leading to regulate ITPR1 stability and function (PubMed:25368151). Plays a role in protection of cells from ER stress-induced apoptosis (By similarity). Protects cells from oxidative stress when overexpressed in cardiomyocytes (By similarity).|||Truncated SELENOK proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(KLHDC2) complex, which recognizes the diglycine (Gly-Gly) at the C-terminus of truncated SELENOK proteins. http://togogenome.org/gene/10090:Vmn1r212 ^@ http://purl.uniprot.org/uniprot/Q8R268 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pbsn ^@ http://purl.uniprot.org/uniprot/O08976|||http://purl.uniprot.org/uniprot/Q3UV89 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Dnajc25 ^@ http://purl.uniprot.org/uniprot/A2ALW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the DNAJC25 family.|||Membrane http://togogenome.org/gene/10090:Ddx4 ^@ http://purl.uniprot.org/uniprot/Q3V086|||http://purl.uniprot.org/uniprot/Q61496 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent RNA helicase required during spermatogenesis to repress transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:20439430, PubMed:28633017). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:20439430, PubMed:28633017). Involved in the secondary piRNAs metabolic process, the production of piRNAs in fetal male germ cells through a ping-pong amplification cycle (PubMed:20439430, PubMed:28633017). Required for PIWIL2 slicing-triggered piRNA biogenesis: helicase activity enables utilization of one of the slice cleavage fragments generated by PIWIL2 and processing these pre-piRNAs into piRNAs (PubMed:28633017).|||Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX4/VASA subfamily.|||Cytoplasm|||Expressed in spermatogenic cells from the spermatocyte stage to the round spermatid stage.|||Found in a mRNP complex, at least composed of TDRD1, TDRD6, TDRD7 and DDX4 (PubMed:17141210). Interacts with RANBP9 (PubMed:14648869, PubMed:27622290). Interacts with RANBP10 (PubMed:27622290). Interacts with PIWIL2 and MAEL (PubMed:14736746, PubMed:16787967). Interacts with BMAL1 and CLOCK (PubMed:22900038). Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886). Interacts with RBM46 (PubMed:36001654).|||Mice are viable but show male sterility due to defects in spermatogenesis. Retrotransposons are derepressed due to DNA demethylation. Defects are caused by impaired piRNA expression.|||Testis-specific.|||perinuclear region http://togogenome.org/gene/10090:Cckar ^@ http://purl.uniprot.org/uniprot/O08786|||http://purl.uniprot.org/uniprot/Q3TPL0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity).|||Receptor for gastrin and cholecystokinin. The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Garem1 ^@ http://purl.uniprot.org/uniprot/Q3UFT3 ^@ Function|||PTM|||Similarity|||Subunit ^@ Acts as an adapter protein that plays a role in intracellular signaling cascades triggered either by the cell surface activated epidermal growth factor receptor and/or cytoplasmic protein tyrosine kinases. Promotes activation of the MAPK/ERK signaling pathway. Plays a role in the regulation of cell proliferation (By similarity).|||Belongs to the GAREM family.|||Interacts with EGFR. Interacts (via proline-rich domain and phosphorylated at Tyr-105 and Tyr-453) with GRB2 (via SH3 domains); the interaction occurs upon EGF stimulation. Interacts (phosphorylated at Tyr-453) with PTPN11; the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation (By similarity).|||On EGF stimulation, phosphorylated on Tyr-105 and Tyr-453. http://togogenome.org/gene/10090:Eif3k ^@ http://purl.uniprot.org/uniprot/Q3TY56|||http://purl.uniprot.org/uniprot/Q9DBZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit K family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Identified in a HCV IRES-mediated translation complex, at least composed of EIF3C, IGF2BP1, RPS3 and HCV RNA-replicon. Interacts with ALKBH4, IFIT1 and IFIT2.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with CCND3, but not with CCND1 and CCND2.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Chst7 ^@ http://purl.uniprot.org/uniprot/Q9EP78 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.|||Golgi apparatus membrane|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues. Preferentially acts on mannose-linked GlcNAc. Also able to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Also acts on core 2 mucin-type oligosaccharide and N-acetyllactosamine oligomer with a lower efficiency. Has weak or no activity toward keratan sulfate and oligosaccharides containing the Galbeta1-4GlcNAc. Catalyzes 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl GalNAc.|||Widely expressed. Highly expressed in kidney. Expressed at lower level in heart, lung and liver. http://togogenome.org/gene/10090:Caly ^@ http://purl.uniprot.org/uniprot/Q9DCA7 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NSG family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Interacts with CLTA.|||Interacts with clathrin light chain A and stimulates clathrin self-assembly and clathrin-mediated endocytosis.|||Mice display impaired clathrin assembly and clathrin-mediated endocytosis. Transgenic mice with up-regulated forebrain expression of Caly display a range of abnormal behaviors including spontaneous hyperactivity, reduced anxiety and/or impaired harm avoidance.|||Most abundant in brain. Also expressed in testis and ovary and, at much lower levels, in kidney and heart.|||The human ortholog was originally thought to interact with the D1 dopamine receptor (DRD1) and to play a role in potentiating calcium ion-dependent signaling but this work was later retracted. http://togogenome.org/gene/10090:Hmgb1 ^@ http://purl.uniprot.org/uniprot/P63158|||http://purl.uniprot.org/uniprot/Q58EV5 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated on multiple sites upon stimulation with LPS (By similarity). Acetylation on lysine residues in the nuclear localization signals (NLS 1 and NLS 2) leads to cytoplasmic localization and subsequent secretion. Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity (By similarity).|||Belongs to the HMGB family.|||Cell membrane|||Chromosome|||Cytoplasm|||Endoplasmic reticulum-Golgi intermediate compartment|||Endosome|||Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers.|||HMG box 2 mediates pro-inflammatory cytokine-stimulating activity and binding to TLR4. However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance.|||In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (PubMed:25642769). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (PubMed:24302768). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (PubMed:17548579).|||In the extracellular compartment (following either active secretion or passive release) involved in regulation of the inflammatory response. Fully reduced HGMB1 (which subsequently gets oxidized after release) in association with CXCL12 mediates the recruitment of inflammatory cells during the initial phase of tissue injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization (PubMed:22370717). Induces the migration of monocyte-derived immature dendritic cells and seems to regulate adhesive and migratory functions of neutrophils implicating AGER/RAGE and ITGAM (PubMed:17268551). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (PubMed:19890330). Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE. Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways (PubMed:17568691, PubMed:19264983, PubMed:21419643). Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12110890, PubMed:17548579). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12. TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2. In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (By similarity). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1R1:IL1RAP receptor complex (By similarity). Binding to class A CpG activates cytokine production in plasmacytoid dendritic cells implicating TLR9, MYD88 and AGER/RAGE and can activate autoreactive B cells. Via HMGB1-containing chromatin immune complexes may also promote B cell responses to endogenous TLR9 ligands through a B-cell receptor (BCR)-dependent and ACER/RAGE-independent mechanism (By similarity). Inhibits phagocytosis of apoptotic cells by macrophages; the function is dependent on poly-ADP-ribosylation and involves binding to phosphatidylserine on the cell surface of apoptotic cells (PubMed:22204001, PubMed:18768881). In adaptive immunity may be involved in enhancing immunity through activation of effector T-cells and suppression of regulatory T (TReg) cells (PubMed:21419643). In contrast, without implicating effector or regulatory T-cells, required for tumor infiltration and activation of T-cells expressing the lymphotoxin LTA:LTB heterotrimer thus promoting tumor malignant progression (PubMed:23108142). Also reported to limit proliferation of T-cells (By similarity). Released HMGB1:nucleosome complexes formed during apoptosis can signal through TLR2 to induce cytokine production (By similarity). Involved in induction of immunological tolerance by apoptotic cells; its pro-inflammatory activities when released by apoptotic cells are neutralized by reactive oxygen species (ROS)-dependent oxidation specifically on Cys-106 (By similarity). During macrophage activation by activated lymphocyte-derived self apoptotic DNA (ALD-DNA) promotes recruitment of ALD-DNA to endosomes (PubMed:25660970).|||In vitro cleavage by CASP1 is liberating a HMG box 1-containing peptide which may mediate immunogenic activity; the peptide antagonizes apoptosis-induced immune tolerance (By similarity). Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and pro-inflammatory activities.|||Interacts (fully reduced HMGB1) with CXCL12; probably in a 1:2 ratio involving two molecules of CXCL12, each interacting with one HMG box of HMGB1; inhibited by glycyrrhizin (PubMed:22370717). Associates with the TLR4:LY96 receptor complex (By similarity). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (PubMed:9184213). Interacts (in cytoplasm upon starvation) with BECN1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with KPNA1; involved in nuclear import (PubMed:17114460). Interacts with SREBF1, TLR2, TLR4, TLR9, APEX1, FEN1, POLB, TERT (PubMed:16040616, PubMed:16267105, PubMed:17548579, PubMed:17803946, PubMed:22544226). Interacts with AGER, PTPRZ1, IL1B, MSH2, XPA, XPC, HNF1A, TP53 (By similarity). Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response (PubMed:19264983). Interacts with THBD; prevents HGMB1 interaction with ACER/RAGE and inhibits HGMB1 pro-inflammatory activity (By similarity). Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (PubMed:22842346). Interacts with XPO1; mediating nuclear export (By similarity). Interacts with receptor RAGE/AGER (By similarity).|||Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability. Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors. In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance (PubMed:23519706, PubMed:23446148, PubMed:23994764, PubMed:25048472). Has proangiogenic activity (PubMed:16365390). May be involved in platelet activation. Binds to phosphatidylserine and phosphatidylethanolamide. Bound to RAGE mediates signaling for neuronal outgrowth. May play a role in accumulation of expanded polyglutamine (polyQ) proteins (By similarity).|||Nuclear functions are attributed to fully reduced HGMB1. Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA, DNA-containing cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity. May be involved in nucleotide excision repair (NER), mismatch repair (MMR) and base excision repair (BER) pathways, and double strand break repair such as non-homologous end joining (NHEJ) (PubMed:17803946, PubMed:18650382). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS). In vitro can displace histone H1 from highly bent DNA. Can restructure the canonical nucleosome leading to relaxation of structural constraints for transcription factor-binding (By similarity). Enhances binding of sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and increases their transcriptional activities (PubMed:16040616). Facilitates binding of TP53 to DNA (By similarity). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (PubMed:21641551, PubMed:24606906). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (PubMed:22544226).|||Nucleus|||Phosphorylated at serine residues (PubMed:17114460). Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (By similarity).|||Plays a role in acute sepsis; administration of antibodies to HMGB1 attenuates endotoxin lethality; administration of HMGB1 itself is lethal (PubMed:10398600). Overexpression in ALD-DNA-immunized mice significantly enhances the severity of modeled SLE (PubMed:26078984).|||Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (PubMed:18768881, PubMed:22204001).|||Rapid death within 24 hours following birth due to hypoglycaemia.|||Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- Fully reduced HGMB1 (HMGB1C23hC45hC106h), 2- Disulfide HMGB1 (HMGB1C23-C45C106h) and 3- Sulfonyl HMGB1 (HMGB1C23soC45soC106so).|||Secreted|||Serum levels are found elevated in mice with modeled systemic lupus erythematosus (SLE) and are correlated with SLE disease activity (PubMed:26078984).|||The acidic C-terminal domain forms a flexible structure which can reversibly interact intramolecularily with the HMG boxes and modulate binding to DNA and other proteins.|||Was reported that reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities. Was reported to be secreted. However, this work was later retracted, although the roles of different redox forms in some functional activities is supported by similarity. http://togogenome.org/gene/10090:Clspn ^@ http://purl.uniprot.org/uniprot/Q80YR7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the claspin family.|||Interacts (phosphorylation-dependent) with CHEK1; regulates CLSPN function in checkpoint for DNA damage and replication. Interacts with ATR and RAD9A and these interactions are slightly reduced during checkpoint activation. Interacts with BRCA1 and this interaction increases during checkpoint activation. Interacts with TIMELESS; the interaction is required for leading-strand replication. Associates with the MCM2-7 complex and other replisome factors. Interacts (via the acidic patch) with CDC7; the interaction is required for phosphorylation of MCM proteins and CLASPIN by CDC7. Interacts with PCNA. Interacts with FZR1.|||Knockout enbryos die by E12.5.|||Nucleus|||Phosphorylated. Undergoes ATR-dependent phosphorylation by CHEK1 during activation of DNA replication or damage checkpoints. Phosphorylation by CSNK1G1/CK1 promotes CHEK1 binding. Phosphorylated by CDC7 during DNA replication, phosphorylation inhibits interaction between the acidic patch and N-terminal segments leading to increased binding to DNA and PCNA.|||Proteolytically cleaved by caspase-7 (CASP7) in response to apoptosis, leading to its inactivation.|||Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:27401717). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (By similarity). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication (PubMed:27401717). Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS. Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (By similarity).|||The C-terminus of the protein contains 3 potential CHEK1-binding motifs (CKB motifs). Potential phosphorylation sites within CKB motif 1 and CKB motif 2 are required for interaction with CHEK1 (By similarity).|||The acidic patch region is required for normal DNA replication. Interacts with the N-terminal segments and inhibits binding to DNA and PCNA. Mediates the interaction with the kinase CDC7 as well as some replisome factors and DNA polymerases.|||Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) during G1 phase, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Following DNA damage, it is deubiquitinated by USP28 in G2 phase, preventing its degradation (By similarity). http://togogenome.org/gene/10090:Or8d6 ^@ http://purl.uniprot.org/uniprot/Q8VH09 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sprr2a2 ^@ http://purl.uniprot.org/uniprot/Q4KL71|||http://purl.uniprot.org/uniprot/Q9CQK8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cornifin (SPRR) family.|||By type-2 cytokines IL4 and IL13 in response to helminth infection.|||Forms five pairs of intrachain disulfide bonds.|||Gut bactericidal protein that selectively kills Gram-positive bacteria by binding to negatively charged lipids on bacterial membranes, leading to bacterial membrane permeabilization and disruption (PubMed:34735226). Specifically binds lipids bearing negatively charged headgroups, such as phosphatidic acid, phosphatidylserine (PS), cardiolipin (CL), and phosphatidylinositol phosphates, but not to zwitterionic or neutral lipids (By similarity). Induced by type-2 cytokines in response to helminth infection and is required to protect against helminth-induced bacterial invasion of intestinal tissue (PubMed:34735226). May also be involved in the development of the cornified envelope of squamous epithelia; however, additional evidences are required to confirm this result in vivo (By similarity).|||Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an expansion of Gram-positive bacteria in the small intestinal lumen and mucus layer (PubMed:34735226). Mice were born in normal Mendelian ratios, are healthy and show normal intestinal morphology with no signs of inflammation in normal conditions (PubMed:34735226). They however show an increased abundance of Gram-positive bacteria in the small intestinal lumen, with a marked increase in the relative abundance of Lactobacillus, Turicibacter, and C.Arthromitus (PubMed:34735226). At the same time, a reduction in the abundance of Bacteroidetes, a class of Gram-negative bacteria is observed (PubMed:34735226). Mice are more susceptible to L. monocytogenes infection (PubMed:34735226).|||Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an expansion of Gram-positive bacteria in the small intestinal lumen and mucus layer (PubMed:34735226). Mice were born in normal Mendelian ratios, are healthy and show normal intestinal morphology with no signs of inflammation in normal conditions (PubMed:34735226). They however show an increased abundance of Gram-positive bacteria in the small intestinal lumen, with a marked increase in the relative abundance of Lactobacillus, Turicibacter, and C.arthromitus (PubMed:34735226). At the same time, a reduction in the abundance of Bacteroidetes, a class of Gram-negative bacteria is observed (PubMed:34735226). Mice are more susceptible to L. monocytogenes infection (PubMed:34735226).|||Secreted|||extracellular space|||secretory vesicle http://togogenome.org/gene/10090:Fbxl5 ^@ http://purl.uniprot.org/uniprot/Q8C2S5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An iron-sulfur cluster promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.|||Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2 (PubMed:21907140, PubMed:23135277). The C-terminal domain of FBXL5 contains a redox-sensitive [2Fe-2S] cluster that, upon oxidation, promotes binding to IRP2 to effect its oxygen-dependent degradation. Under iron deficiency conditions, the N-terminal hemerythrin-like (Hr) region, which contains a diiron metal center, cannot bind iron and undergoes conformational changes that destabilize the FBXL5 protein and cause its ubiquitination and degradation. When intracellular iron levels start rising, the Hr region is stabilized. Additional increases in iron levels facilitate the assembly and incorporation of a redox active [2Fe-2S] cluster in the C-terminal domain. Only when oxygen level is high enough to maintain the cluster in its oxidized state can FBXL5 recruit IRP2 as a substrate for polyubiquination and degradation. Promotes ubiquitination and subsequent degradation of the dynactin complex component DCTN1. Within the nucleus, promotes the ubiquitination of SNAI1; preventing its interaction with DNA and promoting its degradation. Negatively regulates DNA damage response by mediating the ubiquitin-proteasome degradation of the DNA repair protein NABP2 (By similarity).|||FBXL5-deletion mice die during early embryogenesis (PubMed:23135277, PubMed:21907140). FBXL5-null embryos accumulate excess ferrous iron and are exposed to damaging levels of oxidative stress (PubMed:21907140). Simultaneous inactivation of both the FBXL5 and IRP2 genes is sufficient to rescue embryonic lethality (PubMed:21907140).|||Nucleus|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with ACO1/IRP1, IREB2/IRP2; the interaction depends on the [2Fe-2S] cluster. Interacts with DCTN1/p150-glued.|||Polybiquitinated upon iron and oxygen depletion, leading to its degradation by the proteasome. Ubiquitination is regulated by the hemerythrin-like region that acts as an oxygen and iron sensor. Undergoes constitutive ubiquitin-dependent degradation at the steady state by HERC2.|||The hemerythrin-like region acts as an oxygen and iron sensor by binding oxygen through a diiron metal-center. In absence of oxygen and iron, the protein is ubiquitinated and degraded (By similarity).|||Ubiquitously expressed. Highly expressed in early embryogenesis with expression decreasing as the embryo progresses through development (E11 and E15).|||perinuclear region http://togogenome.org/gene/10090:Ddx50 ^@ http://purl.uniprot.org/uniprot/Q99MJ9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.|||Interacts with C1QBP.|||nucleolus http://togogenome.org/gene/10090:Gars ^@ http://purl.uniprot.org/uniprot/Q9CZD3 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis.|||Cytoplasm|||Homodimer.|||Mice (Nmf249) heterozygous for the P278YK variant are used a model for human Charcot-Marie-Tooth 2D (CMT2D), which is caused by dominant GARS mutations. They exhibit reduced amplitudes of muscle compound action potentials and a large reduction in sciatic nerve conduction velocity in the absence of demyelination or remyelination, resulting from an age-related decrease in the number of large myelinated motor and sensory axons. The loss of myelinated axons is length-dependent, and there is a length- and time-dependent decrease in motor innervation of distal versus proximal muscles. Most of the axonal loss occurs by 1 month of age and mice that survive this period can be long-lived. At the molecular level, the P278YK mutation creates a neomorphic binding activity leading to the interaction of the variant with NRP1. This interaction competes out VEGFA binding and inhibits VEGFA-NRP1 signling which is essential for motor neuron survival. VEGFA, but not GDNF treatment significantly ameliorates the loss of motor function in mutant mice.|||Mitochondrion|||Secreted|||axon|||extracellular exosome http://togogenome.org/gene/10090:Lyg2 ^@ http://purl.uniprot.org/uniprot/Q3V1I0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 23 family.|||May act as a potent antibacterial protein that may play a role in the innate immunity.|||Secreted http://togogenome.org/gene/10090:Hs3st5 ^@ http://purl.uniprot.org/uniprot/B2RXW6|||http://purl.uniprot.org/uniprot/Q8BSL4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 1 family.|||Golgi apparatus membrane|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan. Catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact). This modification is a crucial step in the biosynthesis of anticoagulant heparan sulfate as it completes the structure of the antithrombin pentasaccharide binding site. Also generates GlcUA-GlcNS or IdoUA-GlcNS and IdoUA2S-GlcNH2 (By similarity). http://togogenome.org/gene/10090:Slc27a6 ^@ http://purl.uniprot.org/uniprot/E9Q9W4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Cell membrane|||Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane (By similarity). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates (PubMed:15699031). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation such as the heart (By similarity).|||sarcolemma http://togogenome.org/gene/10090:BC004004 ^@ http://purl.uniprot.org/uniprot/Q99KU6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Exhibits histone deacetylase (HDAC) enhancer properties. May play a role in cell cycle progression and wound repair of bronchial epithelial cells.|||Glycosylated.|||Golgi apparatus membrane|||Homodimer (By similarity). Interacts with BRS3. Interacts (via N-terminus) with SIN3B. http://togogenome.org/gene/10090:Tyms ^@ http://purl.uniprot.org/uniprot/P07607|||http://purl.uniprot.org/uniprot/Q544L2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thymidylate synthase family.|||Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway.|||Cytoplasm|||Homodimer.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion matrix|||Nucleus http://togogenome.org/gene/10090:Tas2r134 ^@ http://purl.uniprot.org/uniprot/Q7TQB0 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Or1j11 ^@ http://purl.uniprot.org/uniprot/Q8VGK8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nr2c1 ^@ http://purl.uniprot.org/uniprot/Q505F1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR2 subfamily.|||By ciliary neurotrophic factor (CNTF). Repressed by vitamin A. Induced by retinoic acid.|||Due to intron retention.|||Homodimer. Heterodimer; with NR2C2 which is required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth (By similarity). Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain); the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression.|||Isoform 1 is highly expressed in early to midgestation embryos, with expression leveling off at 15 dpc. Expressed in yolk sac erythrocytes at 9.5 dpc. After birth, expression in the testes remains at a basal level until puberty, begins to increase at postnatal day 16 (P16) and peaks at P20 to P24. Expression is maintained at a high level throughout adulthood. Isoform 2 peaks transiently at P24.|||Isoform 1 is highly expressed in the adlumenal compartment of the seminiferous tubule of adult testes (at protein level) and in the eyes of newborn animals. Weakly expressed in other adult organs including the seminal vesicle, prostate, ovary, adrenal gland, heart, thymus, placenta and brain. Expressed during embryonic stages in developing eyes, brain and cartilage primordia (at protein level). Also expressed in the developing spinal motor neurons and in the sympathetic-, parasympathetic- and sensory ganglia of the embryonic PNS. Expressed in the developing neural epithelia of the inner ear, nasal cavity, tongue and retina. At day 16.5, expressed in various tissues including kidney and intestine. In contrast, isoform 2 is widely expressed at a low level throughout the adult testis.|||No visible phenotype. Mice exhibit normal spermatogenesis and testis development, as well as normal central nervous system development. NR2C1 and NR2C2 double null mutants result in early embryonic lethality and increased apoptosis. Embryos die around 7.5 dpc.|||Nucleus|||Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes including ESR1 and RARB. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences (By similarity). Also activator of OCT4 gene expression. Plays a fundamental role in early embryogenesis and regulates embryonic stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation.|||PML body|||Phosphorylated on several serine and threonine residues. Phosphorylation on Thr-210, stimulated by all-trans retinoic acid (atRA) mediates PML location and sumoylation in proliferating cells which then modulates its association with effector molecules, KAT2B and NRIP1. Phosphorylation on Ser-568 by PKC is important for protein stability and function as activator of RARB.|||Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction with NRIP1 but inhibits interaction with KAT2B. In proliferating cells, stimulation by all-trans retinoic acid, activation of MAPK1-mediated phosphorylation and recruitment to PML bodies with subsequent sumoylation, suppresses OCT4 expression. http://togogenome.org/gene/10090:Spag6l ^@ http://purl.uniprot.org/uniprot/Q9JLI7 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Defects in Spag6 are a cause of hydrocephalus and of male infertility.|||Highly expressed in testis. Not detected in prostate, ovary, spleen, thymus, small intestine, colon and peripheral blood leukocytes.|||Important for structural integrity of the central apparatus in the sperm tail and for flagellar motility.|||In null embryos the central apparatus is unstable leading to a loss, and presumably degradation of proteins to which SPAG6 normally binds, including SPAG16 and SPAG17.|||Interacts with SPAG16 and SPAG17.|||cilium axoneme|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Hdac4 ^@ http://purl.uniprot.org/uniprot/Q6NZM9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone deacetylase family. HD type 2 subfamily.|||Cytoplasm|||Homodimer. Homodimerization via its N-terminal domain (By similarity). Interacts with HDAC7 (PubMed:10984530). Interacts with MEF2A, MEF2C, MEF2D, MORC2 and NR2C1. Interacts with a 14-3-3 chaperone proteins in a phosphorylation dependent manner. Interacts with 14-3-3 protein YWHAB (By similarity). Interacts with BTBD14B. Interacts with KDM5B. Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats). Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2. Interacts with EP300 in the presence of TFAP2C (By similarity). Interacts with AHRR (PubMed:17949687). Interacts with MYOCD (PubMed:15601857). Interacts with HSPA1A and HSPA1B leading to their deacetylation at 'Lys-77' (By similarity). Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression (PubMed:22730529). Interacts with DHX36 (PubMed:21590736). Interacts with SIK3; this interaction leads to HDAC4 retention in the cytoplasm (PubMed:22318228). Interacts with ZNF638 (By similarity).|||Nucleus|||Phosphorylated by CaMK4 at Ser-245, Ser-465 and Ser-629. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-349, within the PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3 (By similarity).|||Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Deacetylates HSPA1A and HSPA1A at 'Lys-77' leading to their preferential binding to co-chaperone STUB1.|||Sumoylation on Lys-556 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.|||The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2.|||The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm. http://togogenome.org/gene/10090:Rgs16 ^@ http://purl.uniprot.org/uniprot/P97428 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with GNAI1 and GNAQ (By similarity). Interacts with GNAI3, GNAI3 and GNAO1 (PubMed:9079700, PubMed:18434540).|||Membrane|||Palmitoylated on Cys-2 and/or Cys-12.|||Phosphorylated. Phosphorylation at Tyr-167 by EGFR enhances GTPase accelerating (GAP) activity toward GNAI1.|||Regulates G protein-coupled receptor signaling cascades (PubMed:9079700). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:10373502). Plays an important role in the phototransduction cascade by regulating the lifetime and effective concentration of activated transducin alpha (PubMed:8917514). May regulate extra and intracellular mitogenic signals.|||Retinal; also predominantly expressed in the liver and pituitary. http://togogenome.org/gene/10090:Cebpg ^@ http://purl.uniprot.org/uniprot/P53568|||http://purl.uniprot.org/uniprot/Q54AJ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. C/EBP subfamily.|||Binds DNA as a dimer and can form stable heterodimers with CEBPA (PubMed:2121606). Can form stable heterodimers with CEBPB (By similarity). Interacts with ZNF638; this interaction increases transcriptional activation (PubMed:21602272).|||Nucleus|||Transcription factor that binds to the promoter and the enhancer regions of target genes (PubMed:21602272). Binds to the promoter and the enhancer of the immunoglobulin heavy chain (PubMed:2121606). Binds to GPE1, a cis-acting element in the G-CSF gene promoter (PubMed:1709121). Binds to the enhancer element PRE-I (positive regulatory element-I) of the IL-4 gene (By similarity). Binds to the promoter and the enhancer of the alpha-1-fetoprotein gene (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Pah ^@ http://purl.uniprot.org/uniprot/P16331|||http://purl.uniprot.org/uniprot/Q3UEH8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.|||Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.|||Homodimer and homotetramer.|||N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an 'inhibitory' domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule.|||Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine. http://togogenome.org/gene/10090:Ces1a ^@ http://purl.uniprot.org/uniprot/E9PYP1|||http://purl.uniprot.org/uniprot/Q5FWH4 ^@ Similarity ^@ Belongs to the type-B carboxylesterase/lipase family. http://togogenome.org/gene/10090:Polr1g ^@ http://purl.uniprot.org/uniprot/Q76KJ5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPA34 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits. Interacts with TAF1A thereby associates with the SL1 complex. Interacts with UBTF (By similarity). Interacts with POLR1E/PRAF1 through its N-terminal region.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors. Involved in UBTF-activated transcription, presumably at a step following PIC formation.|||It is in an antisense orientation to and overlaps the gene of the DNA repair enzyme ERCC1. This gene overlap is conserved in human, suggesting an important biological function.|||nucleolus http://togogenome.org/gene/10090:Ndufb4b ^@ http://purl.uniprot.org/uniprot/Q9CQC7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB4 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nt5dc3 ^@ http://purl.uniprot.org/uniprot/Q3UHB1 ^@ Cofactor|||Similarity ^@ Belongs to the 5'(3')-deoxyribonucleotidase family.|||Binds 1 Mg(2+) ion per subunit. http://togogenome.org/gene/10090:Slc35b4 ^@ http://purl.uniprot.org/uniprot/Q8CIA5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Antiporter that transports nucleotide sugars across the endoplasmic reticulum (ER) membrane in exchange for another nucleotide sugar. May couple UDP-alpha-D-glucuronate (UDP-GlcA) or UDP-alpha-D-xylose (UDP-Xyl) efflux to UDP-alpha-D-glucuronate (UDP-GlcA) influx into the ER lumen, which in turn stimulates glucuronidation and excretion of endobiotics and xenobiotics.|||Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Fam199x ^@ http://purl.uniprot.org/uniprot/Q8K2D0 ^@ Similarity ^@ Belongs to the FAM199 family. http://togogenome.org/gene/10090:Taf15 ^@ http://purl.uniprot.org/uniprot/Q8BQ46 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the RRM TET family.|||Nucleus http://togogenome.org/gene/10090:Nid2 ^@ http://purl.uniprot.org/uniprot/O88322|||http://purl.uniprot.org/uniprot/Q3TPN0|||http://purl.uniprot.org/uniprot/Q8C6Z2|||http://purl.uniprot.org/uniprot/Q8R5G0 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell adhesion glycoprotein. Might be involved in osteoblast differentiation. It probably has a role in cell-extracellular matrix interactions.|||Highly N- and O-glycosylated.|||Interacts with LAMA2. Interacts with COL13A1 (By similarity). Interacts with EFEMP2 (PubMed:17324935).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||basement membrane http://togogenome.org/gene/10090:Phkg2 ^@ http://purl.uniprot.org/uniprot/Q9DB30 ^@ Function|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM (By similarity).|||Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin (By similarity). http://togogenome.org/gene/10090:Or51h5 ^@ http://purl.uniprot.org/uniprot/Q8VGZ3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or2y12 ^@ http://purl.uniprot.org/uniprot/Q7TQT3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ret ^@ http://purl.uniprot.org/uniprot/P35546 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on C-terminal tyrosine residues upon ligand stimulation.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Cell membrane|||Endosome membrane|||Exclusive loss in nociceptors results in a reduction in nociceptor number and size with a reduced epidermal innervation, but increased sensitivity to cold and increased formalin-induced pain.|||Expressed in peripheral nerve cells, hematopoietic cells and podocytes (PubMed:18753381). Expressed in the brainstem, restricted to cells in the area postrema and the immediately adjacent region of the nucleus tractus solitarius (PubMed:28953886).|||Phosphorylated form interacts with the PBT domain of DOK2, DOK4 and DOK5 (PubMed:11470823). The phosphorylated form interacts with PLCG1 and GRB7 (PubMed:8631863). Interacts (not phosphorylated) with PTK2/FAK1 (via FERM domain) (By similarity). Extracellular cell-membrane anchored RET cadherin fragments form complex in neurons with reduced trophic status, preferentially at the contact sites between somas (By similarity). Interacts with AIP in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex (By similarity). Binds to ARTN (PubMed:17322904). Interacts (inactive) with CBLC and CD2AP; dissociates upon activation by GDNF which increases CBLC:CD2AP interaction (PubMed:18753381). Interacts (via the extracellular domain) with GFRAL (via the extracellular domain); the interaction mediates cellular signaling upon interaction of GFRAL with its ligand GDF15 (PubMed:28846099). Interaction with GFRAL requires previous GDF15-binding to GFRAL (PubMed:28846099). Interacts with GFRA1; in the presence of SORL1, the GFRA1/RET complex is targeted to endosomes. Interacts with GDNF (By similarity).|||Proteolytically cleaved by caspase-3. The soluble RET kinase fragment is able to induce cell death. The extracellular cell-membrane anchored RET cadherin fragment accelerates cell adhesion in sympathetic neurons (By similarity).|||Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways (PubMed:28846099).|||Repressed by withaferin A (WA).|||Treatment with withaferin A (WA) leads tumor regression in medullary thyroid carcinomas (MTC). http://togogenome.org/gene/10090:Shroom1 ^@ http://purl.uniprot.org/uniprot/Q5SX79 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the shroom family.|||Interacts with F-actin.|||May be involved in the assembly of microtubule arrays during cell elongation.|||The ASD1 domain mediates F-actin binding.|||cytoskeleton http://togogenome.org/gene/10090:Lrp1b ^@ http://purl.uniprot.org/uniprot/A2API5 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LDLR family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:R3hcc1l ^@ http://purl.uniprot.org/uniprot/Q8BJM3 ^@ Subunit ^@ May interact with the exon junction complex (EJC) composed at least of CASC3, EIF4A3, MAGOH and RBM8A. http://togogenome.org/gene/10090:Vmn1r222 ^@ http://purl.uniprot.org/uniprot/Q8R269 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H2bc15 ^@ http://purl.uniprot.org/uniprot/P10853 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Hsd17b7 ^@ http://purl.uniprot.org/uniprot/O88736 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. ERG27 subfamily.|||Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis (PubMed:9658408, PubMed:12732193, PubMed:12829805, PubMed:20659585). Catalyzes the NADP(H)-dependent reduction of estrogens and androgens and regulates the biological potency of these steroids. Converts estrone (E1)to a more potent estrogen, 17beta-estradiol (E2) (PubMed:9658408, PubMed:12732193). Converts moderately dihydrotestosterone (DHT) to their inactive forms 5a-androstane-3beta,17b-diol and 5alpha-androstane-3alpha,17beta-diol (PubMed:12732193). Does not metabolize progesterone (PubMed:12732193). Additionally, participates in the post-squalene cholesterol biosynthesis, as a 3-ketosteroid reductase (PubMed:12829805, PubMed:20659585).|||Binds to the short form of prolactin receptor.|||Death at embryonic day 10.5. Embryonic lethality is caused by severe brain malformation and heart defect.|||Endoplasmic reticulum membrane|||Most abundant in ovaries of pregnant animals. Present also in nonpregnant animals in ovaries, mammary gland liver, kidney and testis.|||Phosphorylated. http://togogenome.org/gene/10090:Rnase13 ^@ http://purl.uniprot.org/uniprot/Q5GAM7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pancreatic ribonuclease family.|||Does not exhibit any ribonuclease activity.|||Secreted http://togogenome.org/gene/10090:Dmkn ^@ http://purl.uniprot.org/uniprot/Q6P253 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dermokine family.|||Expression begins during the period of stratification at 15.5 dpc, increases up to 17.5 dpc and decreases at 18.5 dpc.|||Highly expressed in stratified epithelia; such as the skin, tongue, esophagus, forestomach and vagina. Also found in lung, trachea and urinary bladder.|||Homooligomer. Seems to be able to homodimerize and homotrimerize (By similarity).|||May act as a soluble regulator of keratinocyte differentiation.|||O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Soat1 ^@ http://purl.uniprot.org/uniprot/Q61263 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.|||Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) preferentially as susbstrate: shows a higher activity towards an acyl-CoA substrate with a double bond at the delta-9 position (9Z) than towards saturated acyl-CoA or an unsaturated acyl-CoA with a double bond at the delta-7 (7Z) or delta-11 (11Z) positions.|||Each protomer consists of 9 transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site: acyl-CoA enters the active site through the cytosolic tunnel, whereas cholesterol enters from the side through the transmembrane tunnel.|||Endoplasmic reticulum membrane|||May form homo- or heterodimers. Interacts with UBIAD1. http://togogenome.org/gene/10090:Zbtb1 ^@ http://purl.uniprot.org/uniprot/Q91VL9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor (By similarity). Represses cAMP-responsive element (CRE)-mediated transcriptional activation (By similarity). In addition, has a role in translesion DNA synthesis. Requires for UV-inducible RAD18 loading, PCNA monoubiquitination, POLH recruitment to replication factories and efficient translesion DNA synthesis (By similarity). Plays a key role in the transcriptional regulation of T lymphocyte development (PubMed:22201126, PubMed:22753936).|||Both the BTB domain and C2H2-type motifs are necessary for transcriptional repression activity. The BTB domain is also necessary for oligomerization and efficient sumoylation. The hydrophobic cluster preceding Lys-328 enhanced sumoylation efficiency (By similarity).|||Expressed strongly in thymus and spleen, less in lymph nodes and peripheral blood mononuclear cells (PBMCs) and weakly in bone marrow. Strongly expressed in immature, but weakly in mature bone marrow-lymphocyte B.|||Homodimer (By similarity). Homodimer (PubMed:22753936). Interacts (via BTB domain) with TRIM28 (unphosphorylated or phosphorylated form) (By similarity).|||Nucleus|||Sumoylated with SUMO2 at Lys-328 and to a lesser extent at Lys-266. Sumoylation inhibits its transcriptional repression activity and regulates its subcellular localization (By similarity).|||The UBZ-type zinc finger domain is required for targeting ZBTB1 to UV damage sites and for PCNA monoubiquitination. UBZ-type zinc finger domain mediates binding to 'Lys-63'-linked polyubiquitin chains (in vitro).|||Thymus of embryos show a small number of T-cell progenitors that are unable to progress through thymic differentiation. Adult mice show vestigial thymus and lymph nodes and a reduced spleen size. In the periphery and in the spleen, display an absence of mature T-cells, a reduced number of NK cells, but a normal number of mature B-cells.|||nucleoplasm http://togogenome.org/gene/10090:Trim47 ^@ http://purl.uniprot.org/uniprot/Q497Z1|||http://purl.uniprot.org/uniprot/Q8C0E3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates the ubiquitination and proteasomal degradation of CYLD.|||Expressed in hepatocytes, expression is increased in fatty livers.|||Nucleus http://togogenome.org/gene/10090:Ror1 ^@ http://purl.uniprot.org/uniprot/Q9Z139 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At postnatal P0, expressed in heart, lung, liver, kidney, spleen and inner ear (PubMed:27162350). In the inner ear, at 14.5 dpc, detected in spiral ganglia, the cochlear epithelium and the vesitbule. At 17.5 dpc, expression increases in spiral ganglion neurons axon terminals adjacent to auditory hair cells. In the differentiating cochlear epithelium, the expression is intense in the stria vascularis. By P0, expression in the stria vascularis is weakened (PubMed:27162350).|||At postnatal P0, expressed in heart, lung, liver, kidney, spleen and inner ear.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.|||Has very low kinase activity in vitro and is unlikely to function as a tyrosine kinase in vivo (By similarity). Receptor for ligand WNT5A which activate downstream NFkB signaling pathway and may result in the inhibition of WNT3A-mediated signaling (By similarity). In inner ear, crucial for spiral ganglion neurons to innervate auditory hair cells (PubMed:27162350).|||Membrane|||Mutant mice are severely deaf, with preserved otoacoustic emissions. They have malformed cochleae with fasciculation defects in axons of spiral ganglion neurons. Type I neurons show impaired synapses with inner hair cells and type II neurons display aberrant projections through the cochlear sensory epithelium.|||axon http://togogenome.org/gene/10090:Tmem138 ^@ http://purl.uniprot.org/uniprot/Q9D6G5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM138 family.|||Required for ciliogenesis.|||Vacuole membrane|||cilium http://togogenome.org/gene/10090:Crkl ^@ http://purl.uniprot.org/uniprot/A2RS58|||http://purl.uniprot.org/uniprot/P47941 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the CRK family.|||Interacts with DOCK2 and EPOR. Interacts with phosphorylated CBLB and IRS4 (By similarity). Interacts with INPP5D/SHIP1 (PubMed:11031258). Interacts with BCAR1/CAS and NEDD9/HEF1 (By similarity).|||May mediate the transduction of intracellular signals.|||Phosphorylated on tyrosine. Phosphorylation is prominent during early development, but decreases at later embryonic stages and in newborn mice. http://togogenome.org/gene/10090:Chd4 ^@ http://purl.uniprot.org/uniprot/Q6PDQ2|||http://purl.uniprot.org/uniprot/Q8BM83 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent helicase that binds and distorts nucleosomal DNA (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:17938210). Localizes to acetylated damaged chromatin in a ZMYND8-dependent manner, to promote transcriptional repression and double-strand break repair by homologous recombination (By similarity). Involved in neurogenesis (PubMed:27806305).|||Belongs to the SNF2/RAD54 helicase family.|||Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:27806305). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:27806305). Interacts with IKFZ1; the interaction is direct and when in part of the NuRD complex (PubMed:11003653). Part of a complex containing ATR and HDAC2 (By similarity). Interacts with HDAC2; the interaction is direct (PubMed:27806305). Interacts with the cohesin complex component RAD21; the interaction is direct (By similarity). Interacts with the ISWI chromatin remodeling complex component SMARCA5; the interaction is direct (By similarity). Interacts with ZGPAT; the interaction is direct (By similarity). Interacts with ZMYND8; the interaction is direct, appears to occur with monomeric ZMYND8, and is increased following DNA damage (By similarity). Interacts with BCL6 (By similarity). Interacts with BRD4 (By similarity). Interacts with CBX1 (By similarity). Interacts with CBX3 (By similarity). Interacts with CBX5 (By similarity). Interacts with GATAD2A (By similarity). Interacts with HDAC1 (By similarity). Interacts with KLF1; the interaction depends on sumoylation of KLF1, and leads to its transcriptional repression (PubMed:17938210). Interacts with MTA1 (By similarity). Interacts with PCNT (By similarity). Interacts with RBBP7 (By similarity). Interacts with SETX (By similarity). Interacts with TRIM27 (By similarity). Interacts with histone H3 (By similarity). Interacts with histone H4 (By similarity). Does not interact with PWWP2A (PubMed:30228260, PubMed:30327463). Does not interact with PWWP2B (PubMed:30228260).|||Expression is constant from 12.5 dpc to 18.5 dpc in the cortex.|||Nucleus|||centrosome http://togogenome.org/gene/10090:Hoxc4 ^@ http://purl.uniprot.org/uniprot/Q08624 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family. Deformed subfamily.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Unk ^@ http://purl.uniprot.org/uniprot/Q3UYU7|||http://purl.uniprot.org/uniprot/Q8BL48 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the unkempt family.|||Cytoplasm|||First expressed at 12 dpc and then expression declines postnatally. Highly expressed in the developing CNS (at protein level).|||Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). http://togogenome.org/gene/10090:Nudt1 ^@ http://purl.uniprot.org/uniprot/P53368 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family.|||Binds 2 Mg(2+) ion per subunit.|||Cytoplasm|||High expression levels detected in thymus, liver, spleen, kidney, testis and large intestine, with lower levels detected in brain, heart, lung and stomach (at protein level). Expressed in kidney, liver and small intestine.|||Monomer.|||Mutant mice appear normal, but have higher incidence of tumors in lung, liver and stomach.|||Nucleus|||Nucleus membrane|||Oxidized purine nucleoside triphosphate hydrolase which is a prominent sanitizer of the oxidized nucleotide pool (PubMed:11572992, PubMed:29281266, PubMed:7592783, PubMed:30304478). Catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP (By similarity). Has also a significant hydrolase activity toward 2-oxo-ATP, 8-oxo-dGTP and 8-oxo-dATP (PubMed:11572992, PubMed:29281266, PubMed:7592783, PubMed:30304478). Through the hydrolysis of oxidized purine nucleoside triphosphates, prevents their incorporation into DNA and the subsequent transversions A:T to C:G and G:C to T:A (PubMed:11572992, PubMed:29281266, PubMed:7592783, PubMed:30304478). Also catalyzes the hydrolysis of methylated purine nucleoside triphosphate preventing their integration into DNA (PubMed:30304478, PubMed:32144205). Through this antimutagenic activity protects cells from oxidative stress (PubMed:11572992, PubMed:29281266, PubMed:7592783, PubMed:30304478, PubMed:32144205).|||acrosome http://togogenome.org/gene/10090:Myg1 ^@ http://purl.uniprot.org/uniprot/Q9JK81 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 3'-5' RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. Involved in regulating spatially segregated organellar RNA processing, acts as a coordinator of nucleo-mitochondrial crosstalk (PubMed:31081026). In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins (PubMed:31081026).|||Belongs to the MYG1 family.|||Mitochondrion matrix|||Mutants are vital, fertile and display no gross abnormalities. They show an inconsistent pattern of altered anxiety-like behavior. Mutant males are significantly less anxious than their wild-type littermates, females show increased anxiety in the locomotor activity arena.|||Strongly up-regulated from 7 dpc to 11 dpc. Widely expressed at 8.5 dpc. At 11.75 dpc, expression is strongest in developing neuroepithelium and eye.|||Ubiquitously expressed, with highest levels in testis.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Or7g18 ^@ http://purl.uniprot.org/uniprot/Q8VFJ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zbtb46 ^@ http://purl.uniprot.org/uniprot/Q8BID6 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Functions as a transcriptional repressor for PRDM1.|||Nucleus|||Sumoylated. Desumoylation by DESI1 reverses transcriptional repression activity. http://togogenome.org/gene/10090:Zfp27 ^@ http://purl.uniprot.org/uniprot/P10077 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Otud4 ^@ http://purl.uniprot.org/uniprot/B2RRE7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein. May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (By similarity).|||Interacts with MYD88; the interaction is direct (PubMed:29395066). Interacts with ALKBH3; the interaction is direct. Interacts with USP7; the interaction is direct. Interacts with USP9X; the interaction is direct (By similarity).|||Mice are born at sub-Mendelian rate.|||Nucleus|||Phosphorylation at Ser-202 and Ser-204 activates 'Lys-63'-specific deubiquitinase activity. Induced upon stimulation with IL1B.|||Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity. http://togogenome.org/gene/10090:Gzmb ^@ http://purl.uniprot.org/uniprot/P04187 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse (PubMed:35705808). It cleaves after Asp (PubMed:35705808). Once delivered into the target cell, acts by catalyzing cleavage of gasdermin-E (GSDME), releasing the pore-forming moiety of GSDME, thereby triggering pyroptosis and target cell death (By similarity). Seems to be linked to an activation cascade of caspases (aspartate-specific cysteine proteases) responsible for apoptosis execution (By similarity). Cleaves caspase-3 and -9 (CASP3 and CASP9, respectively) to give rise to active enzymes mediating apoptosis (PubMed:35705808). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:35705808).|||Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytolytic granule|||Inactivated by the serine protease inhibitor diisopropylfluorophosphate.|||Secreted http://togogenome.org/gene/10090:Or10al5 ^@ http://purl.uniprot.org/uniprot/Q5CZY0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam166c ^@ http://purl.uniprot.org/uniprot/Q9DAS2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CIMIP2 family.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Tram1 ^@ http://purl.uniprot.org/uniprot/Q4FK14|||http://purl.uniprot.org/uniprot/Q91V04 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAM family.|||Endoplasmic reticulum membrane|||Interacts with SEC61B. May interact with Derlin-1/DERL1.|||Involved in the translocation of nascent protein chains into or through the endoplasmic reticulum (ER) membrane by facilitating the proper chain positioning at the SEC61 channel. Regulates the exposure of nascent secretory protein chain to the cytosol during translocation into the ER. May affect the phospholipid bilayer in the vicinity of the lateral gate of the SEC61 channel, thereby facilitating ER protein transport. Intimately associates with transmembrane (TM) domain of nascent membrane proteins during the entire integration process into the ER membrane. Associates with the second TM domain of G-protein-coupled receptor opsin/OPSD nascent chain in the ER membrane, which may facilitate its integration into the membrane. Under conditions of ER stress, participates in the disposal of misfolded ER membrane proteins during the unfolded protein response (UPR), an integrated stress response (ISR) pathway, by selectively retrotranslocating misfolded ER-membrane proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Krt75 ^@ http://purl.uniprot.org/uniprot/Q8BGZ7 ^@ Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the companion layer and upper germinative matrix region of the hair follicle and the medulla of the hair shaft. Also expressed in epithelia of the nail bed and fungiform papillae of dorsal tongue epithelium (at protein level).|||Heterodimer of a type I and a type II keratin (By similarity). May associate with KRT17.|||Its presence in surviving mice lacking Krt6a and Krt6b, may explain the absence of hair and nail defects in such mice.|||Plays a central role in hair and nail formation. Essential component of keratin intermediate filaments in the companion layer of the hair follicle (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Xpo5 ^@ http://purl.uniprot.org/uniprot/Q924C1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the exportin family.|||Component of a nuclear export receptor complex composed of XPO5, RAN, dsRNA-binding proteins and dsRNA. Found in a nuclear export complex with XPO5, RAN, EEF1A1, and aminoacylated tRNA. Found in a nuclear export complex with XPO5, RAN, ILF3 and dsRNA. Found in a nuclear export complex with XPO5, RAN and pre-miRNA. Found in a nuclear export complex with XPO5, RAN, ILF3 and minihelix VA1 dsRNA. Found in a nuclear export complex with XPO5, RAN, ILF3, ZNF346 and dsRNA. Interacts with EEF1A1, ILF3, NUP153, NUP214 and ZNF346. Interacts with RAN and cargo proteins in a GTP-dependent manner. Interacts with ADAR/ADAR1 (via DRBM domains). Interacts with SMAD4; mediates nuclear export of SMAD4. Interacts with RAN (GTP-bound form).|||Cytoplasm|||Mediates the nuclear export of micro-RNA precursors, which form short hairpins. Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference. In some circumstances can also mediate the nuclear export of deacylated and aminoacylated tRNAs. Specifically recognizes dsRNAs that lack a 5'-overhang in a sequence-independent manner, have only a short 3'-overhang, and that have a double-stranded length of at least 15 base-pairs. Binding is dependent on Ran-GTP (By similarity).|||Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and release of the cargo from the export receptor. XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi) (By similarity). Mediates nuclear export of ADAR/ADAR1 in a RanGTP-dependent manner (By similarity).|||Nucleus http://togogenome.org/gene/10090:Polr1a ^@ http://purl.uniprot.org/uniprot/O35134|||http://purl.uniprot.org/uniprot/Q3TU49|||http://purl.uniprot.org/uniprot/Q3UHI3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNA polymerase beta' chain family.|||Chromosome|||Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (By similarity). Interacts with MYO1C (PubMed:16514417). Interacts with ERBB2 (By similarity). Interacts with DDX11 (By similarity). Interacts with RECQL5 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic core component of RNA polymerase I which synthesizes ribosomal RNA precursors. Forms the polymerase active center together with the second largest subunit. A single stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol I. A bridging helix emanates from RPA1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol I by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition (By similarity).|||Phosphorylated.|||nucleolus http://togogenome.org/gene/10090:Extl2 ^@ http://purl.uniprot.org/uniprot/Q3TSR0|||http://purl.uniprot.org/uniprot/Q8C089|||http://purl.uniprot.org/uniprot/Q9ES89 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 47 family.|||Endoplasmic reticulum membrane|||Glycosyltransferase required for the biosynthesis of heparan-sulfate and responsible for the alternating addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine (GlcNAc) units to nascent heparan sulfate chains.|||Membrane http://togogenome.org/gene/10090:Btrc ^@ http://purl.uniprot.org/uniprot/Q3ULA2 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in heart, brain, liver, skeletal muscle and, most strongly, in testis.|||Homodimer. Self-associates. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. Direct interaction with SKP1 with SKP1 occurs via the F-box domain. Interacts with phosphorylated ubiquitination substrates SMAD3 and SMAD4. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A, DLG1, FBXO5 and SNAI1; the interaction requires the phosphorylation of the 2 serine residues in the substrate destruction motif D-S-G-X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts with FBXW11. Interacts with CUL4A and DDB1. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with phosphorylated NKBIA and RELA; RELA interacts directly with NFKBIA. Interacts with the phosphorylated form of GLI3. Interacts with CLU. Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (By similarity). Interacts with ZC3H12A; this interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (PubMed:22037600). Interacts with HSF1; this interaction occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, a process inhibited by CDC20 (By similarity). Interacts with NFE2L1 (PubMed:21911472). Interacts with INAVA (By similarity). Interacts with IL10RA; this interaction leads to IL10RA ubiquitination and subsequent degradation (By similarity). Interacts with REST (By similarity). Interacts with KLF4; this interaction leads to KLF4 ubiquitination and subsequent degradation (PubMed:29593216).|||Mutants have normal circadian behavior with normal PER2 expression in the suprachiasmatic nucleus.|||Nucleus|||PubMed:10531037 wrongly lists the species as human.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:10097128, PubMed:16371461, PubMed:18782782, PubMed:9859996, PubMed:9990853, PubMed:21911472, PubMed:29593216). Recognizes and binds to phosphorylated target proteins (PubMed:10097128, PubMed:16371461, PubMed:18782782, PubMed:9859996, PubMed:9990853, PubMed:21911472). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2. SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (By similarity). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:9859996, PubMed:10097128). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:9859996, PubMed:10097128). The SCF(FBXW11) complex also regulates NF-kappa-B by mediating ubiquitination of phosphorylated NFKB1: specifically ubiquitinates the p105 form of NFKB1, leading to its degradation (By similarity). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (By similarity). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (PubMed:21911472). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:18782782). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase (By similarity). Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF (By similarity). Required for proteolytic processing of GLI3 (PubMed:16371461). Mediates ubiquitination of REST, thereby leading to its proteasomal degradation (By similarity). SCF(BTRC) mediates the ubiquitination and subsequent proteasomal degradation of KLF4; thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216). SCF(BTRC) acts as a regulator of mTORC1 signaling pathway by catalyzing ubiquitination and subsequent proteasomal degradation of phosphorylated DEPTOR, TFE3 and MITF (By similarity).|||The N-terminal D domain mediates homodimerization.|||Ubiquitinated. Deubiquitinated by OTUD5, promoting its stability. http://togogenome.org/gene/10090:Sdhc ^@ http://purl.uniprot.org/uniprot/Q9CZB0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome b560 family.|||Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.|||Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).|||Mitochondrion inner membrane|||The heme b is bound between the two transmembrane subunits SDHC and SDHD. http://togogenome.org/gene/10090:Zfp667 ^@ http://purl.uniprot.org/uniprot/Q2TL60 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Noxo1 ^@ http://purl.uniprot.org/uniprot/Q8VCM2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Constitutively potentiates the superoxide-generating activity of NOX1 and NOX3 and is required for the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. Isoform 3 is more potent than isoform 1 in activating NOX3. Together with NOXA1, may also substitute to NCF1/p47phox and NCF2/p67phox in supporting the phagocyte NOX2/gp91phox superoxide-generating activity.|||Interacts with NOX1, NOXA1, CYBA/p22phox and NCF2/p67phox. Interacts with SH3PXD2A and SH3PXD2B.|||Mice display balance defects being unable to orient themselves with respect to the gravitational force. This is associated with a defect in otoconia biogenesis in the inner ear.|||Strongly expressed by colon epithelial cells and to a lower extent in small intestine, uterus, stomach and testis. Expressed in different parts of the inner ear including sensory and nonsensory cell layers of the saccule, ampullae of the semicircular canals, the stria vascularis and the spiral glanglion neurons.|||Strongly expressed in inner ear during embryogenesis.|||The PX domain mediates lipid-binding, localization to the plasma membrane and is required for NOX1 activation.|||The SH3 domains mediate interaction with CYBA/p22phox. http://togogenome.org/gene/10090:Gm12185 ^@ http://purl.uniprot.org/uniprot/Q5NCB2 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Stpg4 ^@ http://purl.uniprot.org/uniprot/Q9DAG5 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in ovary and testis (PubMed:16571911). Expressed in spermatocytes I in the pachytene stage, round spermatids, and elongated spermatids (PubMed:16571911). Expressed in the germinal vesicle (GV) stage and stage 2 meiosis (MII) oocytes and pre-implantation embryos until blastocyst stage (at protein level) (PubMed:16571911, PubMed:23560077).|||Interacts with histone H3 (PubMed:23560077). Interacts with histone H4 (PubMed:23560077). Interacts with METTL23 (PubMed:28930672).|||Maternal factor that plays a role in epigenetic chromatin reprogramming during early development of the zygote (PubMed:23560077, PubMed:28930672). Involved in the regulation of gametic DNA demethylation by inducing the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) (PubMed:23560077, PubMed:28930672).|||No visible phenotype (PubMed:28930672). Mice were born at the expected Mendelian ratio and show no overt phenotype (PubMed:28930672). Zygotes however display strongly reduced levels of 5-hydroxymethylcytosine (5hmC) (PubMed:28930672).|||Nucleus http://togogenome.org/gene/10090:Pnpla2 ^@ http://purl.uniprot.org/uniprot/Q8BJ56 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15550674, PubMed:23066022, PubMed:15337759, PubMed:16150821, PubMed:16679289, PubMed:17074755, PubMed:16675698, PubMed:17114792). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone and acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (PubMed:23066022). Also possesses acylglycerol transacylase and phospholipase A2 activities (By similarity). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (By similarity). Regulates adiposome size and may be involved in the degradation of adiposomes (By similarity). May play an important role in energy homeostasis (PubMed:16675698). May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion (PubMed:15337759). Catalyzes the formation of an ester bond between hydroxy fatty acids and fatty acids derived from triglycerides or diglycerides to generate fatty acid esters of hydroxy fatty acids (FAHFAs) in adipocytes (PubMed:35676490).|||Cell membrane|||Cytoplasm|||Expressed at high levels in white and brown adipose tissue, and to a lesser degree in testis and cardiac muscle. Barely detected in liver, spleen, thymus, kidney, skeletal muscle, and brain. Among the white adipose depots, gonadal fat showed the highest level of expression compared with inguinal and renal white adipose tissues.|||Increased expression when preadipocytes are induced to differentiate to adipocytes. Not detected in proliferating or confluent preadipocytes.|||Interacts with ABHD5; this association stimulates PNPLA2 triglyceride hydrolase activity (PubMed:16679289, PubMed:17189257). Interacts with SERPINF1; this interaction stimulates the phospholipase A2 activity of PNPLA2 (By similarity). Despite a colocalization in lipid droplets, it probably does not interact with PLIN (PubMed:17189257). Interacts with PLIN5; prevents interaction with ABHD5 (PubMed:21148142, PubMed:21393244). Interacts with FAF2 (By similarity).|||Lipid droplet|||Mice show increased adipose mass and triacylglycerol deposition in multiple tissues. They accumulate large amounts of lipid in the heart, causing cardiac dysfunction and premature death (PubMed:16675698). Conditional knockout in adipose cells results in a marked reduction in the levels and biosynthesis of fatty acid esters of hydroxy fatty acids (FAHFAs) and FAHFA-TGs (PubMed:35676490).|||Phosphorylation at Ser-406 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity.|||Stimulated by PKA-dependent PLIN phosphorylation.|||Transiently induced during fasting. cAMP and glucagon may not be involved in the induction during fasting. Induced by dexamethasone. Down-regulated by insulin, isoprotenerol and TNF-alfa. Expression is not affected by glucose and by growth hormone. Expression is reduced in fasted leptin deficient mouse (ob/ob), an obese mouse model. Expression is not affected in fed ob/ob mouse.|||Ubiquitinated by PEX2 in response to reactive oxygen species (ROS), leading to its degradation. http://togogenome.org/gene/10090:Lce1c ^@ http://purl.uniprot.org/uniprot/Q9D1C5 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Tmem263 ^@ http://purl.uniprot.org/uniprot/Q9DAM7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM263 family.|||May play a role in bone development.|||Membrane http://togogenome.org/gene/10090:Mreg ^@ http://purl.uniprot.org/uniprot/Q6NVG5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the melanoregulin family.|||Cytoplasmic vesicle membrane|||Detected in melanocytes (PubMed:15550542). Expressed in retina, in retinal pigment epithelium (at protein level) (PubMed:17260955, PubMed:19240024). Widely expressed with higher expression in skin, heart, liver, testis and thymus (PubMed:15550542). Detected in retina, in retinal pigment epithelium cells (PubMed:19240024).|||Detected throughout embryogenesis, from 7 dpc to 17 dpc.|||Dilute mice carry a hypomorphic allele of Myo5a, resulting in melanosome clustering in the center of the cell. This causes decreased light absorption and an apparent dilution of coat color. The hair color of mice that are deficient for both Myo5a and Mreg appears nearly normal, but the abnormal clustering of the melanosomes persists (PubMed:15550542, PubMed:3410303, PubMed:22753477). Likewise, mice deficient for Rab27a or Mreg have a gray coat, while mice deficient for Mreg and Rab27a, or Mreg and Mlph, have a hair coat that appears nearly black (PubMed:3410303). In spite of melanosome clustering, shedding of melanosome-containing vesicles and their uptake by adjacent keratinocytes is restored in mice that are deficient for both Myo5a and Mreg (PubMed:22753477). RNAi-mediated knockdown of Mreg in cultured Rab27a-deficient melanocytes restores normal melanosome location at the cell periphery. In cultured wild-type melanocytes melanosomes are dispersed at the cell periphery, and RNAi-mediated knockdown of Mreg has no effect on melanosome location (PubMed:22275436). In mice lacking Mreg, the number of phagosomes in retinal pigment epithelial cells displays a normal, rapid increase after the onset of light, but then decreases much more slowly than in wild-type (PubMed:19240024). Eyecups from 9 and 12 month old mutant mice display increased levels of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2E) (PubMed:19240024).|||Identified in a complex with RILP and DCTN1; interacts directly with RILP, but does not interact directly with DCTN1 (PubMed:22275436). Interacts with PRPH2 (PubMed:17260955).|||Lysosome membrane|||Melanosome membrane|||Palmitoylated. Palmitoylation is required to maintain the protein at the melanosome membrane.|||Probably functions as cargo-recognition protein that couples cytoplasmic vesicles to the transport machinery (PubMed:22940130, PubMed:22275436, PubMed:30174147). Plays a role in hair pigmentation, a process that involves shedding of melanosome-containing vesicles from melanocytes, followed by phagocytosis of the melanosome-containing vesicles by keratinocytes (PubMed:15550542, PubMed:3410303, PubMed:22753477). Functions on melanosomes as receptor for RILP and the complex formed by RILP and DCTN1, and thereby contributes to retrograde melanosome transport from the cell periphery to the center (PubMed:22940130, PubMed:22275436). Overexpression causes accumulation of late endosomes and/or lysosomes at the microtubule organising center (MTOC) at the center of the cell (PubMed:19240024, PubMed:30174147). Probably binds cholesterol and requires the presence of cholesterol in membranes to function in microtubule-mediated retrograde organelle transport (PubMed:30174147). Binds phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate and phosphatidylinositol 3,5-bisphosphate, but not phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 4,5-bisphosphate (PubMed:19240024). Required for normal phagosome clearing and normal activation of lysosomal enzymes in lysosomes from retinal pigment epithelium cells (PubMed:19240024). Required for normal degradation of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2E) in the eye (PubMed:19240024). May function in membrane fusion and regulate the biogenesis of disk membranes of photoreceptor rod cells (Probable). http://togogenome.org/gene/10090:Or1e26 ^@ http://purl.uniprot.org/uniprot/Q8VGT1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppp1r3c ^@ http://purl.uniprot.org/uniprot/Q7TMB3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subunit ^@ Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown. Dramatically increases basal and insulin-stimulated glycogen synthesis upon overexpression in a variety of cell types.|||Interacts with PPP1CC catalytic subunit of PP1 and associates with glycogen. Forms complexes with glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity. Also interacts with EPM2A/laforin.|||Mice display embryonic lethality when homozygous. Heterozygotes display decreased protein levels, decreased glycogen accumulation and glycogen synthase activity, reduced insulin-stimulated glycogen synthesis and progressive age-dependent glucose intolerance. When Ppp1r3c is silenced in adults, they display decreased PP1 activity and glycogen accumulation, increased phosphorylation of glycogen phosphorylase, increased GLUT1 levels, increased glucose uptake and increased glycogen degradation.|||The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase, glycogen synthase and phosphorylase kinase.|||Ubiquitinated by NHLRC1/malin in a EPM2A/laforin-dependent manner. http://togogenome.org/gene/10090:Ssty1 ^@ http://purl.uniprot.org/uniprot/J3QPX2|||http://purl.uniprot.org/uniprot/P13675 ^@ Developmental Stage|||Similarity|||Tissue Specificity ^@ Belongs to the SPIN/STSY family.|||Expressed in testis (at protein level).|||Not detectable at 20 days postpartum (dpp), barely detectable at 22 days postpartum and is strongly detected thereafter (at protein level). Expression is restricted to spermatid stages. http://togogenome.org/gene/10090:4833439L19Rik ^@ http://purl.uniprot.org/uniprot/D3Z1F7|||http://purl.uniprot.org/uniprot/Q9DBN4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the P33MONOX family.|||Cytoplasm|||Expressed in neuronal pyramidal cells of the hippocampus and in the neurons of the cortex.|||Interacts with NELFB, NOL12 and PRNP.|||Potential NADPH-dependent oxidoreductase. May be involved in the regulation of neuronal survival, differentiation and axonal outgrowth (By similarity).|||Potential NADPH-dependent oxidoreductase. May be involved in the regulation of neuronal survival, differentiation and axonal outgrowth. http://togogenome.org/gene/10090:Trappc3l ^@ http://purl.uniprot.org/uniprot/Q4KL14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAPP small subunits family. BET3 subfamily.|||Endoplasmic reticulum|||Homodimer. Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12 (By similarity).|||May play a role in vesicular transport from endoplasmic reticulum to Golgi.|||cis-Golgi network http://togogenome.org/gene/10090:Or2y1f ^@ http://purl.uniprot.org/uniprot/Q8VFA6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Spag8 ^@ http://purl.uniprot.org/uniprot/Q3V0Q6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPAG8 family.|||Cytoplasm|||Expressed in testis (at protein level). Not detected in brain, heart, kidney, spleen, liver, lung, thymus and colon (at protein level).|||In the testis, expressed at low levels at 3 weeks with levels markedly elevated by 4 weeks and into adulthood (at protein level).|||Interacts with FHL5 (via second LIM domain) (PubMed:20488182). Interacts with RANBP9 (By similarity).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). Plays a role in spermatogenesis by enhancing the binding of CREM isoform tau to its coactivator FHL5 and increasing the FHL5-regulated transcriptional activation of CREM isoform tau (PubMed:20488182). Involved in the acrosome reaction and in binding of sperm to the zona pellucida (PubMed:17187156). Plays a role in regulation of the cell cycle by controlling progression through the G2/M phase, possibly by delaying the activation of CDK1 which is required for entry into mitosis (By similarity). May play a role in fertility and microtubule formation through interaction with RANBP9 (By similarity).|||Nucleus|||acrosome|||cilium axoneme|||microtubule organizing center|||spindle http://togogenome.org/gene/10090:Nostrin ^@ http://purl.uniprot.org/uniprot/Q6WKZ7 ^@ Domain|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Homotrimer. Interacts with NOS3, DNM2, WASL and CAV1 (By similarity). Interacts with DAB2.|||In F9 cells, by retinoic acid (at protein level).|||Multivalent adapter protein which may decrease NOS3 activity by inducing its translocation away from the plasma membrane.|||Nucleus|||Seems to repress its own transcription.|||The F-BAR domain is necessary for membrane targeting.|||The SH3 domain mediates interaction with NOS3, DNM2 and WASL.|||cytoskeleton http://togogenome.org/gene/10090:Drd3 ^@ http://purl.uniprot.org/uniprot/A0A2R8VHF0|||http://purl.uniprot.org/uniprot/P30728|||http://purl.uniprot.org/uniprot/Q0VEC4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation (By similarity).|||Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.|||Interacts with CLIC6 (By similarity). Interacts with GRK4. Interacts with PALM. Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA (By similarity).|||Membrane|||Palmitoylated.|||Phosphorylated by GRK4. http://togogenome.org/gene/10090:Ccdc186 ^@ http://purl.uniprot.org/uniprot/Q8C9S4 ^@ Caution|||Sequence Caution|||Tissue Specificity ^@ Contaminating sequence. Potential poly-A sequence.|||Expressed in postnatal germ cells.|||It is uncertain whether Met-1 or Met-19 is the initiator. http://togogenome.org/gene/10090:Fzd4 ^@ http://purl.uniprot.org/uniprot/Q3V1B2|||http://purl.uniprot.org/uniprot/Q61088|||http://purl.uniprot.org/uniprot/Q8BKU9|||http://purl.uniprot.org/uniprot/Q8BLL2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Defects in retinal vascularization.|||Expressed in chondrocytes.|||Interacts with MAGI3 and NDP (PubMed:15035989, PubMed:15195140). Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) (PubMed:19837033). Interacts (via FZ domain) with TSKU; TSKU competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (PubMed:21856951). Interacts with glypican GPC3 (By similarity).|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Receptor for Wnt proteins (PubMed:10097073). Most frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes (PubMed:19837033). Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP) (PubMed:19837033). In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs (PubMed:19837033). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism.|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Rragc ^@ http://purl.uniprot.org/uniprot/Q99K70 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GTR/RAG GTP-binding protein family.|||Cytoplasm|||Expressed most abundantly in kidney. Moderately expressed in brain, ovary, and testis, and detected at lower levels in heart, liver, and muscle. Not detected in lung, spleen, and small intestine. Widely expressed in tumor cells, with expression being specifically up-regulated in highly metastatic cells.|||Forms a heterodimer with RRAGA, in a sequence-independent manner, and RRAGB (By similarity). Heterodimerization stabilizes proteins of the heterodimer (By similarity). The GDP-bound form of RRAGC (in complex with the GTP-bound form of RRAGA or RRAGB), interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (By similarity). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with NOL8 (By similarity). Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGB, is negatively regulated by amino acids and prevents interaction with RPTOR (By similarity). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (By similarity). Interacts with SESN1, SESN2 and SESN3 (PubMed:25259925). Interacts with PIP4P1 (PubMed:29644770). The GDP-bound form interacts with TFEB (By similarity). The GDP-bound form interacts with TFE3 (PubMed:30595499).|||Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagC/RRAGC is in its active form when GDP-bound RagC/RRAGC forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagC/RRAGC heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB). In its GDP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the MTOR signaling cascade by amino acids. Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagC/RRAGC mediates recruitment of MiT/TFE factors TFEB and TFE3.|||Lysosome membrane|||Nucleus|||The activation of RagC/RRAGC is mediated by a GTPase activating protein (GAP) (By similarity). In high-amino acid conditions, activated by GTPase activating protein FLCN that stimulates RRAGC GTPase activity to turn it into its active GDP-bound form (By similarity). In response to amino acid depletion, the GATOR1 complex inactivates RagC/RRAGC by securing the GTP-bound inactive form (By similarity). http://togogenome.org/gene/10090:Pdzd4 ^@ http://purl.uniprot.org/uniprot/Q9QY39 ^@ Subcellular Location Annotation ^@ cell cortex http://togogenome.org/gene/10090:Itga4 ^@ http://purl.uniprot.org/uniprot/Q00651|||http://purl.uniprot.org/uniprot/Q792F9|||http://purl.uniprot.org/uniprot/Q8BQ25 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. The alpha subunit can sometimes be cleaved into two non-covalently associated fragments. Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary complex with CX3CR1 and CX3CL1 (By similarity). Interacts with MDK. ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (By similarity).|||Integrins alpha-4/beta-1 (VLA-4 or LPAM-2) and alpha-4/beta-7 (LPAM-1) are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1.|||Membrane|||Peyer patch homing cells.|||Phosphorylation on Ser-1028 inhibits PXN binding.|||The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion. http://togogenome.org/gene/10090:Rpap2 ^@ http://purl.uniprot.org/uniprot/Q8VC34 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the RNA polymerase II complex. Interacts with transcribing RNA polymerase II phosphorylated on 'Ser-7' on CTD (By similarity).|||Belongs to the RPAP2 family.|||Cytoplasm|||Nucleus|||Protein phosphatase that displays CTD phosphatase activity and regulates transcription of snRNA genes. Recognizes and binds phosphorylated 'Ser-7' of the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and mediates dephosphorylation of 'Ser-5' of the CTD, thereby promoting transcription of snRNA genes (By similarity). Downstream of EIF2AK3/PERK, dephosphorylates ERN1, a sensor for the endoplasmic reticulum unfolded protein response (UPR), to abort failed ER-stress adaptation and trigger apoptosis (PubMed:35975910). http://togogenome.org/gene/10090:Ropn1 ^@ http://purl.uniprot.org/uniprot/Q9ESG2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Ropporin' comes from the Japanese word 'oppo' which means 'tail'.|||Belongs to the ropporin family.|||Expression in testis starts at P21, and increases to reach a plateau at P27 (PubMed:10591629). Expressed in the flagella of sperm at all stages of development in the testis and epididymis (PubMed:23303679).|||Homodimer. Interacts with AKAP3 (By similarity). May interact with SPA17 (By similarity). Interacts with RHPN1 (PubMed:10591629). Interacts with FSCB; the interaction increases upon spermatozoa capacitation conditions (PubMed:27398160).|||Important for male fertility. With ROPN1L, involved in fibrous sheath integrity and sperm motility, plays a role in PKA-dependent signaling processes required for spermatozoa capacitation.|||Mutant mice are subfertile with normal testicular morphology and spermatogenesis but moderately impaired motility and increased levels of ROPN1L (PubMed:23303679). Double knockout animals for ROPN1 and ROPN1L are infertile with normal testicular morphology and spermatogenesis but defects in sperm morphology, thinning and shredding of the principal piece. Sperm is immotile (PubMed:23303679).|||Sumoylated, sumoylation decreases upon spermatozoa capacitation conditions.|||Testis-specific. Present in the most inner parts of seminiferous tubules (at protein level).|||The RIIa domain mediates interaction with AKAP3.|||flagellum http://togogenome.org/gene/10090:Avpi1 ^@ http://purl.uniprot.org/uniprot/Q9D7H4 ^@ Function|||Induction ^@ By vasopressin.|||May be involved in MAP kinase activation, epithelial sodium channel (ENaC) down-regulation and cell cycling. http://togogenome.org/gene/10090:Slc23a1 ^@ http://purl.uniprot.org/uniprot/Q9Z2J0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.|||Cell membrane|||Expressed in kidney (at protein level).|||Phosphorylated.|||Sodium:L-ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each L-ascorbate (PubMed:36749388). Has retained some ancestral activity toward nucleobases such as urate, an oxidized purine. Low-affinity high-capacity sodium:urate cotransporter, may regulate serum urate levels by serving as a renal urate re-absorber (PubMed:36749388) (By similarity). http://togogenome.org/gene/10090:Psen2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1F2|||http://purl.uniprot.org/uniprot/Q3U4P5|||http://purl.uniprot.org/uniprot/Q61144 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase A22A family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer.|||Homodimer. Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist. Interacts with DOCK3. Interacts with HERPUD1, FLNA, FLNB and PARL (By similarity).|||Membrane|||Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins (By similarity). The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is involved in calcium homeostasis (PubMed:16959576). Is a regulator of mitochondrion-endoplasmic reticulum membrane tethering and modulates calcium ions shuttling between ER and mitochondria (By similarity).|||Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors.|||The PAL motif is required for normal active site conformation.|||Ubiquitously expressed. Highly expressed in the liver. http://togogenome.org/gene/10090:Tmed5 ^@ http://purl.uniprot.org/uniprot/A2RS96|||http://purl.uniprot.org/uniprot/Q3V440|||http://purl.uniprot.org/uniprot/Q9CXE7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMP24/GP25L family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Interacts with TMED9 and TMED10.|||Membrane|||Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Required for the maintenance of the Golgi apparatus; involved in protein exchange between Golgi stacks during assembly. Probably not required for COPI-vesicle-mediated retrograde transport (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Galnt16 ^@ http://purl.uniprot.org/uniprot/Q9JJ61 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.|||Golgi apparatus membrane|||In the CNS, it is predominantly expressed in several distinct hypothalamic, thalamic and amygdaloid nuclei. The most abundant level of expression is in the paraventricular, ventromedial and arcuate nuclei of the hypothalamus, the anterodorsal and parafascicular nuclei of the thalamus and the central, basomedial and medial nuclei of the amygdala. Also expressed in cerebral cortex, lateral septum, habenula and hippocampus.|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.|||Was originally termed Galnt10/pp-GaNTase 10. http://togogenome.org/gene/10090:C1d ^@ http://purl.uniprot.org/uniprot/O35473 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the C1D family.|||Cytoplasm|||Kidney, heart, brain, spleen, lung, testis, liver and small intestine.|||Monomer and homodimer. Interacts with EXOSC10; the interaction probably mediates the association with the nuclear form of the RNA exosome. The homodimeric form interacts with TSNAX following gamma-radiation. Interacts with RAC3 (By similarity). Interacts with NR1D1, THRA, THRB, NCOR1 and NCOR2.|||Nucleus|||Phosphorylated by PRKDC.|||Plays a role in the recruitment of the RNA exosome complex to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA; this function may include MPHOSPH6. Can activate PRKDC not only in the presence of linear DNA but also in the presence of supercoiled DNA. Can induce apoptosis in a p53/TP53 dependent manner. May regulate the TRAX/TSN complex formation. Potentiates transcriptional repression by NR1D1 and THRB (By similarity).|||Up-regulated during adipocyte and myogenic differentiation.|||nucleolus http://togogenome.org/gene/10090:Heph ^@ http://purl.uniprot.org/uniprot/A2AI62|||http://purl.uniprot.org/uniprot/Q9Z0Z4 ^@ Cofactor|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the multicopper oxidase family.|||Binds 6 Cu cations per monomer.|||Defects in Heph are a cause of the sex-linked anemia (sla) that is characterized by moderate to severe microcytic hypochronic anemia.|||May function as a ferroxidase for ferrous (II) to ferric ion (III) conversion and may be involved in copper transport and homeostasis. Implicated in iron homeostasis and may mediate iron efflux associated to ferroportin 1.|||Membrane http://togogenome.org/gene/10090:Ankra2 ^@ http://purl.uniprot.org/uniprot/Q99PE2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts (via ANK repeats) with CCDC8 (via PxLPxI/L motif); mediates the interaction with the 3M complex which is composed of CCDC8, CUL7 and OBSL1. Interacts (via ANK repeats) with HDAC4 (via PxLPxI/L motif). Interacts (via ANK repeats) with HDAC5 (via PxLPxI/L motif) (By similarity). Interacts (via ANK repeats) with LRP2/megalin (via PxLPxI/L motif) (PubMed:11095640). Interacts (via ANK repeats) with RFX7 (via PxLPxI/L motif) (By similarity). Interacts with AHRR (PubMed:17949687). Interacts with NEK6 (By similarity).|||May regulate the interaction between the 3M complex and the histone deacetylases HDAC4 and HDAC5 (By similarity). May also regulate LRP2/megalin (PubMed:11095640).|||Membrane|||The ankyrin repeats, mainly ANK 2, ANK 3 and ANK 4, mediate interaction with a wide array of PxLPxI/L motif-containing proteins including HDAC4 and LRP2. The PxLPxI/L motif of interactors can contain a Ser or a Thr residue in position 2, which phosphorylation prevents the interaction with ANKRA2.|||cytoskeleton http://togogenome.org/gene/10090:Rbpms ^@ http://purl.uniprot.org/uniprot/Q9WVB0 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a coactivator of transcriptional activity. Required to increase TGFB1/Smad-mediated transactivation. Acts through SMAD2, SMAD3 and SMAD4 to increase transcriptional activity. Increases phosphorylation of SMAD2 and SMAD3 on their C-terminal SSXS motif, possibly through recruitment of TGFBR1. Promotes the nuclear accumulation of SMAD2, SMAD3 and SMAD4 proteins. Binds to poly(A) RNA.|||Cytoplasm|||Homodimer; each protein chain binds one RNA molecule via the external surface of the homodimer. Interacts with SMAD2, SMAD3 and SMAD4; the interactions are direct.|||Nucleus|||P-body|||The RRM domain is necessary for interaction with SMAD4. Both the RRM domain and the C-terminus are required for TGFB1/Smad-mediated transactivation activity (By similarity).|||mRNA already detected at 9.5 dpc.|||mRNA expressed in developing heart, with significantly higher expression in the atria relative to the ventricles. http://togogenome.org/gene/10090:Il36a ^@ http://purl.uniprot.org/uniprot/Q149U6|||http://purl.uniprot.org/uniprot/Q9JLA2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-1 family.|||By IL-22 in normal and psoriasis-like skin.|||Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. Induces the production of pro-inflammatory cytokines, including IL-12, Il-1 beta, IL-6, TNF-alpha and IL-23 in bone marrow-derived dendritic cells (BMDCs). Involved in dendritic cell maturation by stimulating the surface expression of CD80, CD86 and MHC class II. Induces the production of IFN-gamma, IL-4 and IL-17 by cultured CD4(+) T-cells and splenocytes. May play a role in pro-inflammatory effects in the lung: induces the expression of CXCL1 and CXCL2 in the lung, and the expression of TNF-alpha, IL-36c, IL-1A, IL-1B, CXCL1 and CXCL2 in isolated splenic CD11c(+) alveolar macrophages. May be involved in T-cell maturation by stimulating the surface expression of CD40 and modestly CD80 and CD86 in splenic CD11c(+) cells. May be involved in CD4(+) T-cell proliferation. Induces NF-kappa B activation in macrophages.|||Cytoplasm|||Highly expressed in embryonic tissue and in tissues containing epithelial cells. Elevated expression levels are detected in chronic kidney disease; expressed inepithelia from the distal convoluted tubules (DCTs) to the cortical collecting ducts (CCDs) in single nephrons (at protein level).|||Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||N-terminal truncation leads to a dramatic enhancement of its activity (>1000-fold).|||Secreted http://togogenome.org/gene/10090:H2-Q2 ^@ http://purl.uniprot.org/uniprot/Q4KN81 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Involved in the presentation of foreign antigens to the immune system.|||Membrane http://togogenome.org/gene/10090:Mdk ^@ http://purl.uniprot.org/uniprot/P12025 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pleiotrophin family.|||By retinoic acid (PubMed:2345177). Induced after tissue damage (PubMed:17015789, PubMed:19060126). Induced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions (PubMed:22323540). Induced during the early and intermediate phase of fracture repair (PubMed:25551381).|||Expressed in the follicular epithelium and granulosa cells of the ovary.|||Homodimer. Interacts with ALK. Interacts with LRP1; promotes neuronal survival. Interacts with LRP2. Interacts with NCAM1 (By similarity). Interacts (via C-terminal) with PTPRZ1 (via chondroitin sulfate chains); this interaction is inhibited by PTN; this interaction promotes neuronal migration (PubMed:10212223). Interacts with NCL; this interaction promotes NCL clustering and lateral movements of this complex into lipid rafts leading to MDK internalization. Interacts with LRP6 and LRP8: this interaction is calcium dependent. Interacts with ITGA4. Interacts with ITGA6. Interacts with ITGB1. Interacts with ITGA4:ITGB1 complex; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation. Interacts with ITGA6:ITGB1 complex; this interaction mediates MDK-induced neurite outgrowth. Interacts with NOTCH2; this interactio mediates a nuclear accumulation of NOTCH2 and therefore activation of NOTCH2 signaling leading to interaction between HES1 and STAT3. Interacts with GPC2 (via heparan sulfate chain); this interaction is inhibited by heparin followed by chondroitin sulfate E; this interaction induces GPC2 clustering through heparan sulfate chain; this interaction induces neuronal cell adhesion and neurite outgrowth (By similarity). Interacts with SDC3; this interaction induces SDC3 clustering; this interaction induces neuronal cell adhesion and neurite outgrowth (PubMed:9089390, PubMed:12084985). Interacts with SDC1 (PubMed:9089390). Interacts with CSPG5; this interaction promotes elongation of oligodendroglial precursor-like cells (PubMed:16901907).|||Homozygous knockout MDK mice are viable and reproduce normally. Mice have no apparent abnormalities except that postnatal development of the hippocampus is delayed. However 4 weeks after birth, mice have a deficit in their working memory and have an increased anxiety (PubMed:10096022). Knockout MDK mice exhibit low to moderate levels of auditory deficits and generally respond at around 50 dB. PTN and MDK double knockoutmice have a deficit of auditory response (PubMed:16619002). PTN and MDK double knockout mice are born in only one third the number expected by Mendelian segregation and 4 weeks after birth weigh about half as much as wild-type mice. Most of the female are infertile. Both male and female one-month-old mice show a defect in spontaneous locomotive activity of 50-60% of that of wild-type mice. Although the difference in activity decrease with age, the activity of 3-month-old male double knockout mice is still about 80% of that of the wild-type mice. The diestrus and proestrus periods are long and the estrus period is short. Furthermore, vaginal abnormality is found in about half of the double deficient mice (PubMed:17121547). Homozygous knockout MDK mice display not significant difference from wild-type until the age of 6 month. Mice at 12 and 18 months of age show an increased trabecular bone volume, accompanied by cortical porosity (PubMed:20200993).|||Is expressed temporarily during the early stages of retinoic acid-induced differentiation of embryonal carcinoma cells and during the mid-gestation period of mouse embryogenesis. In late embryos and in adults expression is restricted to the kidney.|||Secreted|||Secreted protein that functions as cytokine and growth factor and mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors (PubMed:16901907). Binds cell-surface proteoglycan receptors via their chondroitin sulfate (CS) groups (PubMed:17230638). Thereby regulates many processes like inflammatory response, cell proliferation, cell adhesion, cell growth, cell survival, tissue regeneration, cell differentiation and cell migration (PubMed:17230638, PubMed:19060126, PubMed:17015789, PubMed:28183532, PubMed:10683378, PubMed:15482347, PubMed:15509530, PubMed:24458438, PubMed:25551381, PubMed:29233575). Participates in inflammatory processes by exerting two different activities. Firstly, mediates neutrophils and macrophages recruitment to the sites of inflammation both by direct action by cooperating namely with ITGB2 via LRP1 and by inducing chemokine expression (PubMed:10683378, PubMed:15509530, PubMed:24458438, PubMed:28183532). This inflammation can be accompanied by epithelial cell survival and smooth muscle cell migration after renal and vessel damage, respectively (PubMed:15509530, PubMed:10683378). Secondly, suppresses the development of tolerogenic dendric cells thereby inhibiting the differentiation of regulatory T cells and also promote T cell expansion through NFAT signaling and Th1 cell differentiation (PubMed:28183532). Promotes tissue regeneration after injury or trauma. After heart damage negatively regulates the recruitment of inflammatory cells and mediates cell survival through activation of anti-apoptotic signaling pathways via MAPKs and AKT pathways through the activation of angiogenesis (PubMed:17015789, PubMed:19060126). Also facilitates liver regeneration as well as bone repair by recruiting macrophage at trauma site and by promoting cartilage development by facilitating chondrocyte differentiation (PubMed:15482347, PubMed:25551381). Plays a role in brain by promoting neural precursor cells survival and growth through interaction with heparan sulfate proteoglycans (PubMed:17230638). Binds PTPRZ1 and promotes neuronal migration and embryonic neurons survival (By similarity). Binds SDC3 or GPC2 and mediates neurite outgrowth and cell adhesion (By similarity). Binds chondroitin sulfate E and heparin leading to inhibition of neuronal cell adhesion induced by binding with GPC2 (PubMed:10978312). Binds CSPG5 and promotes elongation of oligodendroglial precursor-like cells (PubMed:16901907). Also binds ITGA6:ITGB1 complex; this interaction mediates MDK-induced neurite outgrowth (By similarity). Binds LRP1; promotes neuronal survival (By similarity). Binds ITGA4:ITGB1 complex; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (By similarity). Binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase, and the induction of cell proliferation (By similarity). Promotes epithelial to mesenchymal transition through interaction with NOTCH2 (By similarity). During arteriogenesis, plays a role in vascular endothelial cell proliferation by inducing VEGFA expression and release which in turn induces nitric oxide synthase expression. Moreover activates vasodilation through nitric oxide synthase activation (PubMed:29233575). Negatively regulates bone formation in response to mechanical load by inhibiting Wnt/beta-catenin signaling in osteoblasts (PubMed:21185956, PubMed:20200993). In addition plays a role in hippocampal development, working memory, auditory response, early fetal adrenal gland development and the female reproductive system (PubMed:16619002, PubMed:17121547, PubMed:10096022). http://togogenome.org/gene/10090:Gng5 ^@ http://purl.uniprot.org/uniprot/Q3UKC8|||http://purl.uniprot.org/uniprot/Q80SZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||G proteins are composed of 3 units; alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||Membrane http://togogenome.org/gene/10090:Mrpl18 ^@ http://purl.uniprot.org/uniprot/Q9CQL5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL18 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion|||Together with thiosulfate sulfurtransferase (TST), acts as a mitochondrial import factor for the cytosolic 5S rRNA. The precursor form shows RNA chaperone activity; is able to fold the 5S rRNA into an import-competent conformation that is recognized by rhodanese (TST). Both the cytoplasmic and mitochondrial forms are able to bind to the helix IV-loop D in the gamma domain of the 5S rRNA (By similarity). http://togogenome.org/gene/10090:Akirin1 ^@ http://purl.uniprot.org/uniprot/Q99LF1 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 'Akiraka ni suru' means 'making things clear' in Japanese. The name is given based on the presence of the clear nuclear localization signal.|||Belongs to the akirin family.|||Expressed in macrophages and satellite cells.|||Mice grow normally and do not display gross developmental abnormalities (PubMed:18066067). Embryonic fibroblasts obtained from null mutant mice do not express Akirin1 (PubMed:18066067).|||Molecular adapter that acts as a bridge between proteins, and which is involved skeletal muscle development (PubMed:18255059, PubMed:19406121, PubMed:30746755). Functions as signal transducer for MSTN during skeletal muscle regeneration and myogenesis (PubMed:18255059, PubMed:19406121). May regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway (PubMed:19406121). In contrast to AKIRIN2, not involved in nuclear import of proteasomes (By similarity).|||Nucleus|||Up-regulated in activated satellite cells and in the regenerating muscle (PubMed:19406121). Down-regulated by MSTN in skeletal muscle (PubMed:19406121, PubMed:18255059, PubMed:23516508). Down-regulated by dexamethasone by a MSTN (PubMed:23516508). http://togogenome.org/gene/10090:Nat8f1 ^@ http://purl.uniprot.org/uniprot/Q9JIZ0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||May play a role in regulation of gastrulation.|||Membrane http://togogenome.org/gene/10090:Krtap12-1 ^@ http://purl.uniprot.org/uniprot/Q9Z287 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 12 family.|||Expressed only in the head and back skin of a 3 day old mouse. Not expressed in adult skin.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).|||Interacts with hair keratins. http://togogenome.org/gene/10090:Mrpl2 ^@ http://purl.uniprot.org/uniprot/Q9D773 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL2 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Aoc1l2 ^@ http://purl.uniprot.org/uniprot/E9Q745 ^@ Cofactor|||PTM|||Similarity ^@ Belongs to the copper/topaquinone oxidase family.|||Contains 1 topaquinone per subunit.|||Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. http://togogenome.org/gene/10090:Ube2d2a ^@ http://purl.uniprot.org/uniprot/P62838|||http://purl.uniprot.org/uniprot/Q3UT95 ^@ Function|||Similarity|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by RIGI in response to viral infection. Essential for viral activation of IRF3.|||Belongs to the ubiquitin-conjugating enzyme family.|||Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Interacts with CNOT4 (via RING domain). Interacts with E3 ubiquitin-protein ligases CBLC, PJA1 and PJA2. Interacts with PDZRN3. Interacts with PPP1R11 (PubMed:27805901). http://togogenome.org/gene/10090:Coq3 ^@ http://purl.uniprot.org/uniprot/Q8BMS4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. UbiG/COQ3 family.|||Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.|||Mitochondrion inner membrane|||O-methyltransferase that catalyzes the 2 O-methylation steps in the ubiquinone biosynthetic pathway. http://togogenome.org/gene/10090:Tmem240 ^@ http://purl.uniprot.org/uniprot/B2RWJ3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Synapse http://togogenome.org/gene/10090:Rbmxl1 ^@ http://purl.uniprot.org/uniprot/Q91VM5 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||RNA-binding protein which may be involved in pre-mRNA splicing. http://togogenome.org/gene/10090:Scgb2b27 ^@ http://purl.uniprot.org/uniprot/A0A087WRN7|||http://purl.uniprot.org/uniprot/Q8R1E9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Alox12 ^@ http://purl.uniprot.org/uniprot/A2CF85|||http://purl.uniprot.org/uniprot/P39655 ^@ Activity Regulation|||Caution|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by EGF. Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA) (By similarity). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6 (PubMed:11256953).|||Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:8188678, PubMed:11256953, PubMed:25293588). Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE (PubMed:8188678, PubMed:11256953). Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation (PubMed:9501222). It can also catalyze the epoxidation of double bonds of polyunsaturated fatty acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the formation of (13S,14S)-epoxy-DHA. Furthermore, it may participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets (By similarity). An additional function involves a multistep process by which it transforms leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil function via occupancy of specific recognition sites (By similarity). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE) (PubMed:11256953). Due to its role in regulating both the expression of the vascular endothelial growth factor (VEGF, an angiogenic factor involved in the survival and metastasis of solid tumors) and the expression of integrin beta-1 (known to affect tumor cell migration and proliferation), it can be regarded as protumorigenic. Important for cell survival, as it may play a role not only in proliferation but also in the prevention of apoptosis in vascular smooth muscle cells (By similarity).|||Found primarily in platelets and in microsomal and cytosolic fractions of the epidermis (at protein level).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mice are fertile and appear to exhibit no gross abnormalities. However, they display increased aggregation of platelets in response to ADP. They also display a mild basal transepidermal water loss.|||cytosol http://togogenome.org/gene/10090:Cenpa ^@ http://purl.uniprot.org/uniprot/O35216 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H3 family.|||Component of centromeric nucleosomes, where DNA is wrapped around a histone octamer core. The octamer contains two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers. CENPA modulates the DNA-binding characteristics of nucleosomes so that protruding DNA ends have higher flexibility than in nucleosomes containing conventional histone H3. Inhibits binding of histone H1 to nucleosomes, since histone H1 binds preferentially to rigid DNA linkers that protrude from nucleosomes. Nucleosomes containing CENPA also contain histone H2A variants such as MACROH2A and H2A.Z/H2AZ1. The CENPA-H4 heterotetramer is more compact and structurally more rigid than corresponding H3-H4 heterotetramers. Can assemble into nucleosomes that contain both CENPA and histone H3.3; these nucleosomes interact with a single CENPC chain. Heterotrimer composed of HJURP, CENPA and histone H4, where HJURP interacts with the dimer formed by CENPA and histone H4 and prevents tetramerization of CENPA and H4. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Interacts (via CATD domain) with HJURP; the interaction is direct and is required for its localization to centromeres. Interacts with CENPC, CENPN and CENPT; interaction is direct. Part of a centromere complex consisting of CENPA, CENPT and CENPW. Identified in centromere complexes containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Can self-associate. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro). Interacts with CDK1, PPP1CA and RBBP7.|||Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes. Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore. The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3. May serve as an epigenetic mark that propagates centromere identity through replication and cell division (By similarity). Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:27499292).|||Nucleus|||Phosphorylated by CDK1 at Ser-62 during early mitosis; this abolishes association with chromatin and centromeres, prevents interaction with HJURP and thereby prevents premature assembly of CENPA into centromeres. Dephosphorylated at Ser-62 by PPP1CA during late mitosis.|||Poly-ADP-ribosylated by PARP1.|||The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA. It is necessary and sufficient to mediate the localization into centromeres.|||Trimethylated by NTMT1 at the N-terminal glycine after cleavage of Met-1. Methylation is low before incorporation into nucleosomes and increases with cell cycle progression, with the highest levels in mitotic nucleosomes.|||centromere http://togogenome.org/gene/10090:Unc79 ^@ http://purl.uniprot.org/uniprot/Q0KK59 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxiliary subunit of the NALCN sodium channel complex. The NALCN sodium channel complex is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability. Activated by neuropeptides substance P, neurotensin, and extracellular calcium that regulates neuronal excitability by controlling the sizes of NALCN-dependent sodium-leak current.|||Belongs to the unc-79 family.|||Cell membrane|||NALCN complex consists of NALCN and auxiliary subunits, UNC79, UNC80 and NACL1. These auxiliary subunits are essential for the NALCN channel function (By similarity). UNC80 bridges NALCN to UNC79 (PubMed:21040849). Interacts with NALCN (PubMed:21040849). Interacts with UNC80 (PubMed:21040849, PubMed:32620897). http://togogenome.org/gene/10090:Ak1 ^@ http://purl.uniprot.org/uniprot/Q9R0Y5 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylate kinase family. AK1 subfamily.|||Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP (By similarity). Exhibits nucleoside diphosphate kinase activity, catalyzing the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and dTTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donor (By similarity). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (By similarity). May provide a mechanism to buffer the adenylate energy charge for sperm motility (PubMed:16790685).|||Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis.|||Cytoplasm|||Monomer.|||Up-regulated during late spermiogenesis, when the flagellum is being assembled. http://togogenome.org/gene/10090:Slc25a42 ^@ http://purl.uniprot.org/uniprot/Q8R0Y8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial carrier mediating the transport of coenzyme A (CoA) in mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3',5'-diphosphate.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nags ^@ http://purl.uniprot.org/uniprot/Q8R4H7 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the acetyltransferase family.|||Highly expressed in the liver and small intestine. Weakly expressed in the kidney, spleen and testis.|||Homodimer (By similarity). Homotetramer (PubMed:23894642).|||Increased by L-arginine.|||Mitochondrion matrix|||Plays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPS1) activity.|||Probably processed by mitochondrial processing peptidase (MPP). The long form has not yet been isolated.|||The amino-acid kinase (AAK) domain mediates binding of the allosteric activator L-arginine. http://togogenome.org/gene/10090:Dok1 ^@ http://purl.uniprot.org/uniprot/P97465|||http://purl.uniprot.org/uniprot/Q3UWF9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DOK family. Type A subfamily.|||Constitutively tyrosine-phosphorylated. Phosphorylated by TEC. Phosphorylated on tyrosine residues by the insulin receptor kinase. Results in the negative regulation of the insulin signaling pathway (By similarity). Phosphorylated by LYN. Phosphorylated on tyrosine residues by SRMS (By similarity).|||Cytoplasm|||DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK1 appears to be a negative regulator of the insulin signaling pathway. Modulates integrin activation by competing with talin for the same binding site on ITGB3 (By similarity).|||Expressed in lung, spleen, skeletal muscle and kidney.|||Interacts with RasGAP, INPP5D/SHIP1 and ABL1. Interacts directly with phosphorylated ITGB3 (By similarity). Interacts with SRMS (via the SH2 and SH3 domains) (By similarity).|||No visible phenotype. Mice appear healthy and are fertile.|||Nucleus|||PTB domain mediates receptor interaction. http://togogenome.org/gene/10090:Ctc1 ^@ http://purl.uniprot.org/uniprot/E0CXE7|||http://purl.uniprot.org/uniprot/Q5SUQ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTC1 family.|||Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha. The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins. Involved in telomere maintenance. Involved in genome stability (By similarity). May be in involved in telomeric C-strand fill-in during late S/G2 phase (PubMed:22748632).|||Component of the CST complex, composed of TEN1/C17orf106, CTC1/C17orf68 and STN1; in the complex interacts directly with STN1. Interacts with ACD and POT1 (By similarity).|||Nucleus|||telomere http://togogenome.org/gene/10090:Htr2a ^@ http://purl.uniprot.org/uniprot/P35363|||http://purl.uniprot.org/uniprot/Q543D4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasmic vesicle|||Detected in neurons in brain cortex. Detected in adult intestine, especially in mucosal epithelium, longitudinal and circular layers of muscularis externa and myenteric plexuses. Highly expressed in Paneth cells, and detected at lower levels in enterocytes (at protein level). Detected in neurons in the brain cortex.|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin).|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.|||Interacts with MPDZ and PATJ. May interact with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2 (By similarity). Interacts with GRM2 and DRD2; this may affect signaling.|||Membrane|||Mutant mice display increased exploratory behavior in open spaces and reduced anxiety-like behavior (PubMed:16873667). Mutant mice fail to show behavorial responses to psychoactive substances and hallucinogens, such as mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane and lysergic acid diethylamide (LSD) (PubMed:17270739). Besides, the colon from mutant mice does not contract in response to 5-hydroxytryptamine (PubMed:11960784).|||Presynapse|||Synapse|||The PDZ domain-binding motif is involved in the interaction with PATJ, CASK, APBA1, DLG1 and DLG4.|||Vesicle|||axon|||caveola|||dendrite http://togogenome.org/gene/10090:Kcp ^@ http://purl.uniprot.org/uniprot/Q3U492 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By renal stresses.|||Enhances bone morphogenetic protein (BMP) signaling in a paracrine manner. In contrast, it inhibits both the activin-A and TGFB1-mediated signaling pathways.|||Interacts with BMP7 and, by doing so, enhances binding to the type I receptors that contains cytoplasmic serine-/threonine protein kinase domains. Also able to interact with activin-A and TGFB1.|||Prominently expressed in two areas, the limb buds and the developing kidney, with diffuse staining in the central nervous system. At 9.5 dpc the limb bud mesenchyme is positive. Expression in the kidney region could be detected as early as 9 dpc in the intermediate mesoderm. By 10 dpc, the mesonephric tubules and nephric ducts are clearly positive. At later stages, high levels are localized to the developing tubules. At 18.5 dpc, it is localized to more mature renal tubules located in the developing cortex with little expression detected in the nephrogenic zone.|||Secreted|||Weakly expressed in embryonic kidney and brain. Not expressed in adult tissues and several cell lines. http://togogenome.org/gene/10090:Socs4 ^@ http://purl.uniprot.org/uniprot/Q91ZA6 ^@ Domain|||Function ^@ SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits EGF signaling by mediating the degradation of the Tyr-phosphorylated EGF receptor/EGFR (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Cnot11 ^@ http://purl.uniprot.org/uniprot/Q9CWN7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNOT11 family.|||Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is required for the association of CNOT10 with the CCR4-NOT complex. Seems not to be required for complex deadenylase function (By similarity).|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. CNOT10 and CNOT11 form a subcomplex docke to the CNOT1 scaffold (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Bfsp2 ^@ http://purl.uniprot.org/uniprot/Q6NVD9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cell membrane|||Cytoplasm|||Detected in retina lens fiber cells (at protein level) (PubMed:7679620, PubMed:12454043, PubMed:15037121, PubMed:14985306, PubMed:19029034, PubMed:21745462, PubMed:27559293). Also expressed in the lens epithelium, abundantly expressed in the anterior and anterolateral epithelium, less frequently expressed nearer the lens coronal equator (at protein level) (PubMed:27559293).|||Expressed in the retinal lens fiber cells from postnatal day 28 (P28) to P45 (PubMed:27559293). Expressed in retinal lens beaded filament structures from P37 onwards (PubMed:27559293).|||In strains 101, 129/SvJ and CBA, a polymorphism deletes the acceptor site of exon 2 which causes exon 1 to be spliced to exon 3 and generates a frameshift and premature stop codon (PubMed:12573667, PubMed:15037121). The polymorphism leads to retinal lens fiber cell nuclear opacity beginning at 1 month of age, opacity becomes more pronounced with age (PubMed:14985306). Reduced intermediate filaments and loss of the association of the lens fiber cell cytoskeleton with the plasma membrane (PubMed:15037121, PubMed:14985306).|||No overall change in lens fiber cell organization, regularity of hexagonal profiles, or positioning of cell nuclei (PubMed:12454043). Opacification of the retinal lens is evident at 1 month of age, with progressive loss of clarity to 10 months of age (PubMed:12454043). Reduced abundance and loss of distinction of intermediate filaments in retinal lens fiber cells (PubMed:15037121). Decreased protein abundance of BFSP1 in the retinal lens (PubMed:12454043). Complete loss of beaded filament structures in lens epithelial cells (PubMed:27559293). BFSP2 and VIM double knockout mice show a complete loss of the cytoplasmic cytoskeleton in retinal lens fiber cells (PubMed:15037121).|||Part of a complex required for lens intermediate filament formation composed of BFSP1, BFSP2 and CRYAA (By similarity). Found in a complex composed of PPL (via C-terminal linker domain), BFSP1 and BFSP2 in the retinal lens (PubMed:19029034). Within the complex interacts with PPL (via C-terminal linker domain) and with BFSP1 (PubMed:19029034). Identified in a complex that contains VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (PubMed:21745462). Interacts with LGSN (PubMed:18178558). Interacts with VIM (PubMed:19029034).|||Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA (PubMed:15037121, PubMed:27559293). Plays a role in maintenance of retinal lens optical clarity (PubMed:12454043).|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Poglut1 ^@ http://purl.uniprot.org/uniprot/Q8BYB9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 90 family.|||Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C (PubMed:21949356, PubMed:26496195). Specifically targets extracellular EGF repeats of protein such as CRB2, F7, F9 and NOTCH2 (PubMed:21949356, PubMed:26496195). Acts as a positive regulator of Notch signaling by mediating O-glucosylation of Notch, leading to regulate muscle development (By similarity). Notch glucosylation does not affect Notch ligand binding (By similarity). Required during early development to promote gastrulation: acts by mediating O-glucosylation of CRB2, which is required for CRB2 localization to the cell membrane (PubMed:26496195).|||Endoplasmic reticulum lumen|||Mutant embryos die at or before 9.5 dpc. At 7.0 to 7.5 dpc, they cannot be morphologically distinguished from wild-type littermates (PubMed:21490058, PubMed:26496195). At 8.0 dpc, mutant embryos exhibit an abnormally expanded neural plate that does not fold properly, absence of heart rudiments and posterior axis truncation (PubMed:21490058). Defects are caused by a deficit of mesoderm caused by impaired gastrulation.|||Widely expressed in newborn and adult tissues (at protein level). http://togogenome.org/gene/10090:Car4 ^@ http://purl.uniprot.org/uniprot/Q64444 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-carbonic anhydrase family.|||Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.|||Cell membrane|||Inhibited by acetazolamide.|||Interacts with SLC4A4. http://togogenome.org/gene/10090:B9d2 ^@ http://purl.uniprot.org/uniprot/Q3UK10 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the B9D family.|||Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.|||Highest expression in thymus and skeletal muscle. Also expressed in spleen, kidney, lung, heart, microglia and liver. Detected in brain (at protein level).|||Mice expressing reduced levels of the protein in the central nervous system and kidney develop perinatal triventricular hydrocephaly, polycystic kidney disease, lack functional intact cilia and die at the time of weaning.|||Nucleus|||Part of the tectonic-like complex (also named B9 complex). Interacts with TUBG1.|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Shoc2 ^@ http://purl.uniprot.org/uniprot/O88520 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SHOC2 family.|||Cytoplasm|||Interacts with M-Ras/MRAS, and RAF1. Forms a multiprotein complex with Ras (M-Ras/MRAS), Raf (RAF1) and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with ERBIN; disrupts the interaction with RAF1 and Ras, leading to prevent activation of the Ras signaling pathway. Specifically binds K-Ras/KRAS, M-Ras/MRAS and N-Ras/NRAS but not H-Ras/HRAS. Interacts with LZTR1.|||Nucleus|||Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes. http://togogenome.org/gene/10090:Serpinh1 ^@ http://purl.uniprot.org/uniprot/P19324 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.|||By heat shock and retinoic acid.|||Endoplasmic reticulum lumen http://togogenome.org/gene/10090:Slit2 ^@ http://purl.uniprot.org/uniprot/A0A140T8T2|||http://purl.uniprot.org/uniprot/G3UY21|||http://purl.uniprot.org/uniprot/G3UYX7|||http://purl.uniprot.org/uniprot/Q9R1B9 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:10864955 is expressed during retinal development by 14.5 dpc throughout the RGC layer, and is clearly restricted to the inner nuclear layer at 17.5 dpc. In the developing optic chiasm is strongly expressed at 12.5 dpc at the ventral midline of the diencephalon in the region in which the RGC axons enter the brain and turn to grow ventrally, the region expression includes the position of the glial knot. At 14.5 dpc expression is maintained at the ventral midline of the diencephalon, in a region directly dorsal to the site of axon divergence. Outside the developing brain. According to PubMed:10433822 prominently expressed in neural and mesodermally derived tissues. From 8.5 dpc to 9.5 dpc expressed strongly in the roof plate, floor plate, and notochord. Beginning at 10.5 dpc intense expression is also observed in the motor columns. By 13.5 dpc the expression decreased in the roof plate but is still retained in the floor plate and motor columns. In the rostral CNS between 8.5 dpc and 9.5 dpc expressed intensely in the dorsal neuroepithelium overlying the hindbrain, in the dorsal midline of the midbrain and forebrain, and in the ventral midbrain region. By 10.5 dpc to 11.5 dpc, additional intense expression is observed in the rhombic lip and the rostral midline. From 13.5 dpc to 17.5 dpc, the expression decreased dorsally and continued to be detected in the ventral mesencephalon and diencephalon. Outside neuronal development expressed between 8.5 dpc and 9.5 dpc in the clefts between the first, the second, and the third branchial arches. From 10.5 dpc to 11.5 dpc, expression is detected in the nasal pit, the developing eye, the otic vesicle, and the visceral grooves. From 13.5 dpc to 17.5 dpc expressed in the developing cochlea (in a pattern consistent with expression in the organ of Corti), in the olfactory epithelium and in the inner neuronal layer of the retina and in the optic nerve. At this stage also expressed in the tongue, in the tooth primordium, and in the outer root sheath of the whisker follicle in the layer surrounding the bulb. At 11.5 dpc is intensely expressed in the rostral lateral ridge flanking the forelimb buds and in lateral ridge tissue between the fore- and the hindlimb buds. Weak expression is observed in a segmented pattern in the posterior part of the sclerotome. Expression is notably absent in the base of the limb buds and weak expression is observed in the interdigital regions of the distal limb bud beginning at 11.5 dpc. By 13.5 dpc intensely expressed in interdigital mesenchyme.|||Expressed in developing eye, in the optic stalk, and in the ventral diencephalon.|||Homodimer. Interacts with GREM1 (By similarity). Binds ROBO1 and ROBO2 with high affinity.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice show significant axon guidance errors in a variety of pathways, including corticofugal, callosal and thalamocortical tracts. Mice double-deficient in SLIT1 and SLIT2 show retinal axon guidance defects and a disorganized lateral olfactory tract (LOT).|||Secreted|||The leucine-rich repeat domain is sufficient for guiding both axon projection and neuronal migration, in vitro.|||Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal cord development, may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth-stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal cord midline post-crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system, appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration (By similarity). http://togogenome.org/gene/10090:Rusc1 ^@ http://purl.uniprot.org/uniprot/Q8BG26 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated component of the adapter-like complex 4 (AP-4) (By similarity). Interacts with IKBKG and TRAF6 (By similarity). Interacts with F-actin, acetylated actin, TUBB3, STX1A, KIF5B and KLC1 (PubMed:22404429).|||Associates with the adapter-like complex 4 (AP-4) and may therefore play a role in vesicular trafficking of proteins at the trans-Golgi network. Signaling adapter which plays a role in neuronal differentiation. Involved in regulation of NGF-dependent neurite outgrowth (By similarity). May play a role in neuronal vesicular trafficking, specifically involving pre-synaptic membrane proteins (PubMed:22404429). Seems to be involved in signaling pathways that are regulated by the prolonged activation of MAPK. Can regulate the polyubiquitination of IKBKG and thus may be involved in regulation of the NF-kappa-B pathway (By similarity).|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Expressed at 15 dpc in hippocampal, cortical and cerebellar brain, and brain stem and spinal cord. At 18 dpc, expression strongly overlaps with TUBB3 expression in post-mitotic neurons throughout the entire brain. Expression levels increase to 18 dpc/P1 after which the levels decline in the hippocampus, cerebellum and brain stem and spinal cord into adulthood while remaining high in the cortex.|||Expressed in brain, brain stem and spinal cord (at protein level).|||Golgi apparatus|||Nucleus|||Phosphorylated on serine residues following nuclear translocation.|||Polyubiquitinated; polyubiquitination involves TRAF6.|||Postsynaptic density|||The RUN domain is necessary for NGF induced nuclear redistribution.|||cytoskeleton http://togogenome.org/gene/10090:Angpt2 ^@ http://purl.uniprot.org/uniprot/O35608 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal (By similarity). Involved in the regulation of lymphangiogenesis (PubMed:32908006).|||Expressed only at sites of vascular remodeling.|||Interacts with TEK/TIE2, competing for the same binding site as ANGPT1. Interacts with ITGA5.|||Secreted|||The Fibrinogen C-terminal domain mediates interaction with the TEK/TIE2 receptor. http://togogenome.org/gene/10090:Cat ^@ http://purl.uniprot.org/uniprot/P24270 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the catalase family.|||Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide. Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells.|||Homotetramer. Interacts (via microbody targeting signal) with PEX5, monomeric form interacts with PEX5, leading to its translocation into peroxisomes.|||Peroxisome http://togogenome.org/gene/10090:Dynlt2a1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J284|||http://purl.uniprot.org/uniprot/P11985 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein light chain Tctex-type family.|||Could be involved in transmission ratio distortion (trd) in mouse t-haplotype which causes male sterility.|||Cytoplasmic granule|||Expressed in testis (at protein level). Expressed at the pachyten stage of the first meiotic division and in later haploid spermatogenic stages.|||Interacts with CSNK2B.|||May be an accessory component of axonemal dynein and cytoplasmic dynein 1. Candidate for involvement in male sterility.|||Membrane|||cytoskeleton http://togogenome.org/gene/10090:Or52a5b ^@ http://purl.uniprot.org/uniprot/E9Q7C5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sphkap ^@ http://purl.uniprot.org/uniprot/E9PUC4 ^@ Similarity ^@ Belongs to the AKAP110 family. http://togogenome.org/gene/10090:Oplah ^@ http://purl.uniprot.org/uniprot/Q8K010 ^@ Function|||Similarity|||Subunit ^@ Belongs to the oxoprolinase family.|||Catalyzes the cleavage of 5-oxo-L-proline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate.|||Homodimer. http://togogenome.org/gene/10090:Casp3 ^@ http://purl.uniprot.org/uniprot/P70677 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C14A family.|||Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa.|||Cytoplasm|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce.|||Highest expression in spleen, lung, liver, kidney and heart (PubMed:9038361). Lower expression in brain, skeletal muscle and testis (PubMed:9038361).|||Lethality; the majority of mice on the 129/Svj background die in utero or within weeks of birth because of many extra cells within the brains of these animals (PubMed:8934524). Defects are caused by impaired apoptosis (PubMed:8934524). Mice lacking Casp3 on the C57BL/6J background are viable (PubMed:16469926). Mice lacking Casp3 and Casp7 on the C57BL/6J background die immediately after birth because of defective heart development (PubMed:16469926). This suggests that Casp7 can partially rescue Casp3 in certain conditions (PubMed:16469926).|||S-nitrosylated on its catalytic site cysteine in unstimulated cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol.|||Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:8934524, PubMed:16469926). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:8934524, PubMed:16469926). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage (By similarity). Cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes (By similarity). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:12124386). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (By similarity). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:25231987, PubMed:33725486). http://togogenome.org/gene/10090:Nlrc4 ^@ http://purl.uniprot.org/uniprot/Q3UP24 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed by intestinal mononuclear phagocytes.|||Homooligomer; homooligomerizes following activation of Naip proteins by pathogenic proteins such as S.typhimurium (Salmonella) flagellin or PrgJ (PubMed:23765277, PubMed:26449474, PubMed:26585513, PubMed:29146805). Component of the NLRC4 inflammasome, at least composed of NLRC4, caspase-1 (CASP1) and some NAIP protein (Naip, Naip2 or Naip5) (PubMed:21874021, PubMed:21918512, PubMed:26585513). Interacts with Naip5 and Naip6; following Naip5 and Naip6 engagement by Salmonella flagellin (PubMed:21874021, PubMed:21918512, PubMed:29182158, PubMed:29146805). Interacts with Naip2; following Naip2 engagement by Salmonella PrgJ (PubMed:21874021, PubMed:21918512, PubMed:26449474). The inflammasome is a huge complex that contains multiple copies of NLRC4 and a single Naip protein chain (PubMed:26449474, PubMed:29146805). Some NLRC4 inflammasomes contain PYCARD/ASC, while some others directly contact and activate CASP1 (PubMed:21147462). Interacts with EIF2AK2/PKR (By similarity).|||In an autoinhibited form the C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. An ADP-mediated interaction between the NBD and the WHD also contributes to the autoinhibition (PubMed:23765277).|||Inflammasome|||Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. It senses pathogenic proteins of the type III secretion system (T3SS) and type IV secretion system (T4SS) such as flagellin and PrgJ-like rod proteins via the Naip proteins (Naip1, Naip2 or Naip5): specific Naip proteins recognize and bind pathogenic proteins, driving assembly and activation of the NLRC4 inflammasome. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri and fungal pathogen C.albicans. In intestine, the NLRC4 inflammasome is able to discriminate between commensal and pathogenic bacteria and specifically drives production of interleukin-1 beta (IL1B) in response to infection by Salmonella or P.aeruginosa. In case of L.pneumophila infection the inflammasome acts by activating caspase-7.|||Mice show defects in inflammasome function in response to S.typhimurium (Salmonella) infection. Differences are however observed depending on the strain background: in a C57BL/6J strain background, no striking differences are observed compared to wild-type mice following Salmonella infection. While in a BALB/c strain background, mice are highly susceptible to orogastric but not intraperitoneal infection with Salmonella: enhanced lethality is preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment and poor intestinal pathogen clearance.|||Phosphorylated at Ser-533 following infection of macrophages with S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4 inflammasome function to promote caspase-1 activation and pyroptosis. PRKCD phosphorylates Ser-533 in vitro.|||cytosol http://togogenome.org/gene/10090:Vmn1r166 ^@ http://purl.uniprot.org/uniprot/D3YTY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Klhdc10 ^@ http://purl.uniprot.org/uniprot/Q6PAR0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KLHDC10 family.|||Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter KLHDC10 (By similarity). Interacts (via the 6 Kelch repeats) with PPP5C (PubMed:23102700).|||Cytoplasm|||No visible phenotype in normal conditions (PubMed:27631783). Mice are protected against TNF-alpha-induced systemic inflammation: they show a reduction in the inflammatory response, but not in early systemic necroptosis (PubMed:27631783).|||Nucleus|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (By similarity). The CRL2(KLHDC10) complex specifically recognizes proteins with a proline-glycine (Pro-Gly) or an alanine tail (CAT tail) at the C-terminus, leading to their ubiquitination and degradation (By similarity). The CRL2(KLHDC10) complex is involved in the ribosome-associated quality control (RQC) pathway, which mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes: CRL2(KLHDC10) acts downstream of NEMF and recognizes CAT tails associated with stalled nascent chains, leading to their ubiquitination and degradation (By similarity). Participates in the oxidative stress-induced cell death through MAP3K5 activation (By similarity). Inhibits PPP5C phosphatase activity on MAP3K5 (PubMed:23102700). Acts as a regulator of necroptosis (PubMed:27631783). http://togogenome.org/gene/10090:Bcar1 ^@ http://purl.uniprot.org/uniprot/Q3TJP4|||http://purl.uniprot.org/uniprot/Q61140 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A serine-rich region promotes activation of the serum response element (SRE).|||Belongs to the CAS family.|||Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL SH2 domains. The HLH motif is absolutely required for the induction of pseudohyphal growth in yeast and mediates heterodimerization with NEDD9.|||Cytoplasm|||Dephosphorylated by PTPN14 at Tyr-132.|||Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion (By similarity). Implicated in induction of cell migration and cell branching (PubMed:25499443). Involved in the BCAR3-mediated inhibition of TGFB signaling (PubMed:25499443).|||Expressed in olfactory sensory neurons (at protein level) (PubMed:20881139). Expressed abundantly in the liver, lung, brain, and at lower levels in the heart (at protein level) (PubMed:19365570).|||Forms complexes in vivo with PTK2/FAK1, adapter protein CRKL and LYN kinase. Can heterodimerize with NEDD9. Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK (By similarity). Within the complex, interacts with SH2D3C (via C-terminus), and CRK (By similarity). Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on intergrin mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Interacts with BCAR3 (via Ras-GEF domain); the interaction regulates adhesion-dependent serine phosphorylation (PubMed:10896938, PubMed:22801373). Interacts with SMAD2 and SMAD3 (PubMed:25499443). Interacts with NPHP1 (PubMed:10739664). Interacts with PTK2B/PYK2 (By similarity). Interacts (via C-terminus) with SH2D3C/CHAT isoform 2 (via C-terminus) (PubMed:10692442, PubMed:12486027, PubMed:17174122). Interacts with activated CSPG4. Interacts with BMX, INPPL1/SHIP2 and PEAK1 (By similarity). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas (By similarity). Interacts with TNK2 via SH3 domains. Interacts (when tyrosine-phosphorylated) with tensin TNS1; the interaction is increased by phosphorylation of TNS1 (By similarity).|||PTK2/FAK1 activation mediates phosphorylation at the YDYVHL motif; phosphorylation is most likely catalyzed by SRC family members. SRC-family kinases are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues. Tyrosine phosphorylation is triggered by integrin mediated adhesion of cells to the extracellular matrix (By similarity).|||Phosphorylated by SRC kinase in a EDN1- and PTK2B-mediated manner; phosphorylation strengthens its interaction with BCAR3 as part of the PTK2B/BCAR1/BCAR3/RAP1 signaling pathway.|||The SH3 domain is necessary for the localization of the protein to focal adhesions and interacts with one proline-rich region of PTK2/FAK1.|||axon|||focal adhesion http://togogenome.org/gene/10090:Trim60 ^@ http://purl.uniprot.org/uniprot/Q8VI40 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity ^@ Belongs to the TRIM/RBCC family.|||E3 SUMO-protein ligase that mediates SUMOylation of TAB2 leading to inhibition of NF-kappa-B and MAPK pathways by suppressing the TRAF6/TAB2/TAK1 complex.|||Expressed exclusively in embryos before or up to the 8-cell stage.|||TRIM60-deficient mice show an elevated immune response to LPS-induced septic shock and L. monocytogenes infection. http://togogenome.org/gene/10090:Tcf7l2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1G0|||http://purl.uniprot.org/uniprot/D3YWT3|||http://purl.uniprot.org/uniprot/E9Q990|||http://purl.uniprot.org/uniprot/E9QQ90|||http://purl.uniprot.org/uniprot/E9QQ91|||http://purl.uniprot.org/uniprot/F6WBK9|||http://purl.uniprot.org/uniprot/F6WPX2|||http://purl.uniprot.org/uniprot/Q8BS68|||http://purl.uniprot.org/uniprot/Q8CAI6|||http://purl.uniprot.org/uniprot/Q924A0 ^@ Developmental Stage|||Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCF/LEF family.|||Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC).|||Detected in adult brain and liver, and at lower levels in intestine, with a clear increase from the distal colon to the duodenum. Detected at low levels in heart, lung, kidney, pituitary and testis.|||Dominant negative form which cannot bind CTNNB1. Expression is VAX2-dependent.|||First detected at 10.5 dpc. Highly expressed at 13.5 dpc-16.5 dpc in the central nervous system, in particular in the roof of the mesencephalon, at the ditelencephalic junction and in dorsal thalamus. At 13.5 dpc, detected at low levels in gastrointestinal epithelia.|||Interacts with TGFB1I1 (PubMed:16291758). Interacts with SPIN1 (By similarity). Interacts with CTNNB1 (via the armadillo repeat); forms stable transcription complex (PubMed:19816403). Interacts with EP300. Interacts with NLK. Interacts with CCDC85B (probably through the HMG box); prevents interaction with CTNNB1 (By similarity). Interacts with TNIK (PubMed:19816403). Interacts with MAD2L2; prevents TCF7L2/TCF4 binding to promZIPK/DAPK3oters, negatively modulating its transcriptional activity. Interacts with ZIPK/DAPK3. Interacts with XIAP/BIRC4 and TLE3. Interacts with DDIT3/CHOP. The CTNNB1 and TCF7L2/TCF4 complex interacts with PML (isoform PML-4). Identified in a complex with CTNNB1 and FERMT2. Interacts with C11orf84/SPINDOC in a SPIN1-dependent manner (By similarity). Interacts with DAZAP2; the interaction results in localization of DAZAP2 to the nucleus (By similarity).|||May result from the retention of an intron in the cDNA.|||Nucleus|||PML body|||Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif CCTTTGATC in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1 (By similarity). Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.|||Phosphorylated at Thr-178 and/or Thr-189 by NLK. Phosphorylation by NLK at these sites inhibits DNA-binding by TCF7L2/TCF4, thereby preventing transcriptional activation of target genes of the canonical Wnt/beta-catenin signaling pathway (By similarity).|||Polysumoylated. Sumoylation is enhanced by PIAS family members and desumoylation is enhanced by SENP2. Sumoylation/desumoylation regulates TCF7L2/TCF4 transcription activity in the Wnt/beta-catenin signaling pathway without altering interaction with CTNNB1 nor binding to DNA (By similarity). http://togogenome.org/gene/10090:Ift70a2 ^@ http://purl.uniprot.org/uniprot/A2AKQ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TTC30/dfy-1/fleer family.|||Interacts wit the IFT B complex component IFT52.|||Required for polyglutamylation of axonemal tubulin. Plays a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip.|||cilium http://togogenome.org/gene/10090:Has2 ^@ http://purl.uniprot.org/uniprot/P70312 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NodC/HAS family.|||Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation (By similarity). This is one of three isoenzymes responsible for cellular hyaluronan synthesis and it is particularly responsible for the synthesis of high molecular mass hyaluronan (PubMed:10455188).|||Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction and it is particularly responsible for the synthesis of high molecular mass hyaluronan (PubMed:10455188). Required for the transition of endocardial cushion cells into mesenchymal cells, a process crucial for heart development (PubMed:10930438). May also play a role in vasculogenesis. High molecular mass hyaluronan also play a role in early contact inhibition a process which stops cell growth when cells come into contact with each other or the extracellular matrix.|||Cell membrane|||Detected from 7.5 dpc through birth. At 8.5 dpc, predominantly expressed in the epithelium of the foregut diverticulum, the cephalic mesenchyme, the allantois, and in the myocardium and endocardium of the heart. At 9.5 dpc, prominent expression is detected in cephalic, foregut and periaortic mesenchymes, the septum transversum and the cardiovascular system. Also present in the atrial and ventricular endothelium and the myocardium of the atrioventricular canal region. By 10.5 dpc, highly expressed in endothelial cells in the atrioventricular canal and outflow tract that transform into mesenchymal cells and invade the underlying matrix. Later, expressed by mesenchymal cells during elevation of the secondary palate and by hypertrophic chondrocytes within epiphysial growth plates.|||Embryonic lethal. At day 9.5 dpc, the distribution of homozygous embryos approaches Mendelian frequency while only occasional viable embryos were found at 10.5 dpc. Embryos exhibited growth retardation, scant numbers of red blood cells, and lacked vitelline vessels in the yolk sac. The visceral endoderm and mesoderm forming the yolk sac was not fused except at discrete foci. The heart was thinwalled and relatively bloodless, and often exhibited marked pericardial swelling. The heart lacks cardiac jelly, endocardial cushions and trabeculae. A marked reduction in vessels in homozygous embryos is also observed. Somites were present but distorted. Some of the 9.5 dpc embryos had failed to turn, and exhibited posterior defects as well as cephalic mesenchyme abnormalities.|||Endoplasmic reticulum membrane|||Expressed in heart, brain, spleen, lung and skeletal muscle.|||Golgi apparatus membrane|||Homodimer; dimerization promotes enzymatic activity. Forms heterodimer with HAS3. Forms heterodimer with HAS1.|||Lysosome|||O-GlcNAcylation at Ser-221 increases the stability of HAS2 and plasma membrane localization.|||Phosphorylation at Thr-328 is essential for hyaluronan synthase activity.|||Ubiquitination at Lys-190; this ubiquitination is essential for hyaluronan synthase activity and homo- or hetero-oligomerization. Can also be poly-ubiquitinated. Deubiquitinated by USP17L22/USP17 and USP4. USP17L22/USP17 efficiently removes 'Lys-63'- and 'Lys-48'-linked polyubiquitin chains, whereas USP4 preferentially removes monoubiquitination and, partially, both 'Lys-63'- and 'Lys-48'-linked polyubiquitin chain.|||Vesicle http://togogenome.org/gene/10090:Lipa ^@ http://purl.uniprot.org/uniprot/Q3TEL5|||http://purl.uniprot.org/uniprot/Q9Z0M5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Catalyzes the deacylation of triacylglyceryl and cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol.|||Expressed at low levels in most tissues. High level expression is found in hepatocytes and splenic and thymic cells. Very high level expression is observed in cells of the small intestinal villi, the zona fasciculata and reticularis of the adrenal cortex, pancreatic acini, and renal tubular epithelium.|||Glycosylation is not essential for catalytic activity.|||Lysosome|||Monomer. http://togogenome.org/gene/10090:Jchain ^@ http://purl.uniprot.org/uniprot/P01592 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of the secretory IgA (sIgA) complex that consists of two, four or five IgA monomers, and two additional non-Ig polypeptides, namely the JCHAIN and the secretory component (the proteolytic product of PIGR).|||Secreted|||Serves to link two monomer units of either IgM or IgA. In the case of IgM, the J chain-joined dimer is a nucleating unit for the IgM pentamer, and in the case of IgA it induces dimers and/or larger polymers. It also helps to bind these immunoglobulins to secretory component. http://togogenome.org/gene/10090:Usf2 ^@ http://purl.uniprot.org/uniprot/Q64705 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer (USF1/USF2). Interacts with MAF.|||Nucleus|||Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. http://togogenome.org/gene/10090:Chrna10 ^@ http://purl.uniprot.org/uniprot/B2RX82 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Nmnat1 ^@ http://purl.uniprot.org/uniprot/Q3V449|||http://purl.uniprot.org/uniprot/Q9EPA7 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD).|||Belongs to the eukaryotic NMN adenylyltransferase family.|||By neuronal injury.|||Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:15381699, PubMed:27735788). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (By similarity). Can use triazofurin monophosphate (TrMP) as substrate (By similarity). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (By similarity). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively (By similarity). Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5 (By similarity). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (By similarity). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (By similarity). Also acts as a cofactor for glutamate and aspartate ADP-ribosylation by directing PARP1 catalytic activity to glutamate and aspartate residues on histones (PubMed:32822587). Protects against axonal degeneration following mechanical or toxic insults (PubMed:15310905, PubMed:16914673). Delays axonal degeneration after axotomy. Results in a >10-fold increase in intact neurites 72 hours after injury (PubMed:16914673, PubMed:27735788).|||Divalent metal cations. Zn(2+) confers higher activity as compared to Mg(2+).|||Expressed throughout development and in adulthood.|||Homohexamer (By similarity). Interacts with ADPRT/PARP1 (PubMed:32822587).|||In strain C57BL/Ola, an 85 kb region on chromosome 4 containing Nmnat1 and Ube4b is triplicated. The N-terminal 70 residues of Ube4b becomes linked to the complete Nmnat1 protein and encodes a fusion protein located in the nucleus which is responsible for the Wallerian degeneration slow (Wlds) phenotype characterized by delayed Wallerian degeneration of injured axons.|||Nucleus http://togogenome.org/gene/10090:Ppan ^@ http://purl.uniprot.org/uniprot/Q91YU8 ^@ Function|||Subcellular Location Annotation ^@ May have a role in cell growth.|||nucleolus http://togogenome.org/gene/10090:1700102P08Rik ^@ http://purl.uniprot.org/uniprot/Q9D9C7 ^@ Disruption Phenotype|||Function|||Tissue Specificity ^@ Essential for normal spermatogenesis and male fertility.|||Male mice are infertile with smaller testis and epididymis, but female mice retain normal fertility (PubMed:31930642). Spermatogenesis in the male mouse is arrested at the spermatocyte stage, and no sperm is found in the epididymis (PubMed:31930642). Germ cells apoptosis is increased without changes to the serum concentration of testosterone, LH, and FSH or synapsis and recombination during meiosis (PubMed:31930642).|||Testis-specific. Highly expressed in spermatocytes (at protein level). http://togogenome.org/gene/10090:Chrna1 ^@ http://purl.uniprot.org/uniprot/P04756|||http://purl.uniprot.org/uniprot/Q05A24 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-subfamily.|||Cell membrane|||Membrane|||One of the alpha chains that assemble within the acetylcholine receptor, a pentamer of two alpha chains, a beta, a delta, and a gamma (in immature muscle) or epsilon (in mature muscle) chains (PubMed:17643119). The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (By similarity).|||Postsynaptic cell membrane|||Synaptic cell membrane|||Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. http://togogenome.org/gene/10090:Sphk2 ^@ http://purl.uniprot.org/uniprot/Q9JIA7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, expression is relatively ubiquitous with the strongest signals detected in the limb buds, eyes and branchial arches and a weaker expression in the telencephalon and spinal cord.|||Catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions (PubMed:16118219, PubMed:17346996, PubMed:21084291). Also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:16118219, PubMed:10751414). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12. In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (By similarity). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (PubMed:17346996). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (PubMed:25637806). Also involved in the regulation of glucose and lipid metabolism (PubMed:30593892).|||Cell membrane|||Cleaved by CASP1 in apoptotic cells. The truncated form is released from cells.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in heart, brain, liver, kidney and testis (PubMed:10751414). Expressed by mast cells (at protein level) (PubMed:17346996). In the substantia nigra, expressed by dopaminergic neurons (at protein level) (PubMed:25637806).|||Expressopm decreases upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is used to induce Parkinson disease in mouse model.|||Interacts with histone H3. Interacts with HDAC1, HDAC2, MBD2 and SIN3A. Interacts with EEF1A1; the interaction enhances SPHK2 kinase activity (By similarity). Interacts with PHB2 (PubMed:20959514).|||Lysosome membrane|||Mitochondrion inner membrane|||Mutant mice are viable, fertile and have normal longevity. They show reduced SPP levels (PubMed:16314531). Mice have decreased fat mass but increased lean mass, they display increased energy expenditure compared to wild-type. Aging mice are protected from metabolic decline and obesity. 52-week old male mutant mice have decreased weight and fat mass, and increased glucose tolerance and insulin sensitivity compared to control mice (PubMed:30593892). Double knockout for SPHK1 and SPHK2 causes embryonic lethality (PubMed:16314531). Between 11.5 dpc and 12.5 dpc embryos exhibit cranial hemorrhage and die at 13.5 dpc (PubMed:16314531). At 11.5 dpc the wall of the dorsal aorta is poorly developed and endothelial cells are severely defective in all blood vessels in the mesenchymal region of the head (PubMed:16314531). Embryos also show a neural tube defect (PubMed:16314531).|||Nucleus|||Phosphorylated by PKD on Ser-384 and Ser-386 upon PMA treatment. Phosphorylation induces export from the nucleus to the cytoplasm. Phosphorylated by MAPK1 and MAPK2 at Thr-578, phosphorylation is induced by agonists such as EGF and PMA and increases kinase activity. http://togogenome.org/gene/10090:Pcbp4 ^@ http://purl.uniprot.org/uniprot/P57724 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Single-stranded nucleic acid binding protein that binds preferentially to oligo dC.|||Widely expressed, with highest levels in testis and lowest in heart. http://togogenome.org/gene/10090:Ankrd16 ^@ http://purl.uniprot.org/uniprot/A2AS55 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with AARS; the interaction is direct.|||No visible phenotype (PubMed:29769718). Loss of Ankrd16 in mice with a 'sticky' phenotype (mice homozygous for the variant 'Glu-734' in Aars/AlaRS) results in early embryonic lethality (PubMed:29769718). Conditional deletion in postnatal Purkinje cells in mice with a 'sticky' phenotype exacerbates the 'sticky' phenotype and causes widespread protein aggregation and neuron loss (PubMed:29769718).|||Nucleus|||Required to prevent the misactivation of serine (Ser) with tRNA(Ala) by promoting the hydrolysis of Ser-mischarged tRNA(Ala), thereby playing a role in translational fidelity (PubMed:29769718). Binds directly to the catalytic domain of AARS/AlaRS and captures Ser that is misactivated by AARS/AlaRS, preventing the charging of Ser adenylates to tRNA(Ala) and precluding Ser misincorporation in nascent peptides (PubMed:29769718).|||Side chains of Lys-102, Lys-135 and Lys-165 capture Ser that is misactivated by AARS/AlaRS.|||Widely expressed in brain (at protein level). http://togogenome.org/gene/10090:Pskh1 ^@ http://purl.uniprot.org/uniprot/Q91YA2 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity depends on Ca(2+) concentration.|||Autophosphorylated on serine residues.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Golgi apparatus|||Homodimer.|||May be a SFC-associated serine kinase (splicing factor compartment-associated serine kinase) with a role in intranuclear SR protein (non-snRNP splicing factors containing a serine/arginine-rich domain) trafficking and pre-mRNA processing.|||Myristoylated. Required for membrane association. Prerequisite for palmitoylation to occur (By similarity).|||Nucleus speckle|||Palmitoylated.|||centrosome http://togogenome.org/gene/10090:Rpl18a ^@ http://purl.uniprot.org/uniprot/P62717 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL20 family.|||Component of the large ribosomal subunit (PubMed:36517592). Binds IPO9 with high affinity (By similarity).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm http://togogenome.org/gene/10090:Reep3 ^@ http://purl.uniprot.org/uniprot/A0A1W2P8A8|||http://purl.uniprot.org/uniprot/Q99KK1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DP1 family.|||Endoplasmic reticulum membrane|||Membrane|||Microtubule-binding protein required to ensure proper cell division and nuclear envelope reassembly by sequestering the endoplasmic reticulum away from chromosomes during mitosis. Probably acts by clearing the endoplasmic reticulum membrane from metaphase chromosomes (By similarity). http://togogenome.org/gene/10090:Akna ^@ http://purl.uniprot.org/uniprot/Q80VW7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AKNA family.|||Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (PubMed:30787442). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (PubMed:30787442). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (PubMed:30787442). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (PubMed:30787442). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (By similarity). Binds to A/T-rich promoters (By similarity). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable).|||During development, expressed when the subventricular zone (SVZ) is generated (low at 11 dpc, high at 14 dpc and low at 18 dpc).|||Expressed in neural stem cells isolated at the peak of subventricular zone (SVZ): localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells and in almost all basal progenitors.|||Interacts with DCTN1 (PubMed:30787442). Interacts with MAPRE1/EB1 (PubMed:30787442). Interacts with ODF2 (PubMed:30787442). Interacts with CAMSAP3 (PubMed:30787442).|||Neonatal lethality: mice fail to thrive and most of them die by postnatal day 10 (PubMed:21606955). Mice display systemic inflammation, predominantly in the lungs, accompanied by enhanced leukocyte infiltration and alveolar destruction (PubMed:21606955).|||Nucleus|||Phosphorylated; phosphorylation regulates dissociation from and reassembly at the centrosome.|||centriole http://togogenome.org/gene/10090:Spring1 ^@ http://purl.uniprot.org/uniprot/Q8BTG6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPRING family.|||Golgi apparatus membrane|||Interacts with SCAP.|||Knockout leads to early embryonic lethality.|||Positively regulates hepatic SREBP signaling pathway by modulating the proper localization of SCAP (SREBP cleavage-activating protein) to the endoplasmic reticulum, thereby controlling the level of functional SCAP (PubMed:32111832). Plays a crucial role during embyrogenesis (PubMed:32111832).|||Ubiquitously expressed with a slightly higher expression in the liver and kidney. http://togogenome.org/gene/10090:Ckap2l ^@ http://purl.uniprot.org/uniprot/Q7TS74 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 10.5 dpc, strongly expressed in the neural progenitor cells throughout the neural tube and in the myotome. Expression is significantly lower in connective tissues compared to neural tube, but can be detected at the mitotic spindles of dividing mesenchymal cells loosely distributed in the developing limb bud. In an 12.5 dpc forelimb bud, detected in the dividing cells at the boundary region between protruding cartilage and surrounding mesenchyme (at protein level).|||Belongs to the CKAP2 family.|||Highly expressed in regions of active neurogenesis and neural stem/progenitor cells (NSPCs), both embryonic and adult, not detected in lung, liver, kidney, heart, and skeletal muscle.|||Microtubule-associated protein required for mitotic spindle formation and cell-cycle progression in neural progenitor cells.|||The KEN box is required for the association with the APC/C-Cdh1 complex, ubiquitination and degradation.|||Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C).|||spindle pole http://togogenome.org/gene/10090:Plvap ^@ http://purl.uniprot.org/uniprot/Q91VC4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Endothelial cell-specific membrane protein involved in the formation of the diaphragms that bridge endothelial fenestrae. It is also required for the formation of stomata of caveolae and transendothelial channels. Functions in microvascular permeability, endothelial fenestrae contributing to the passage of water and solutes and regulating transcellular versus paracellular flow in different organs. Plays a specific role in embryonic development.|||Expressed in embryo at 7 dpc. Expressed in the brain vasculature at 12 up to 16 dpc, whereupon it disappears.|||Expressed in lung, kidney, spleen, heart, muscle, eye, pancreas, thyroid, thymus, submaxillary gland, prostate, epididymis, uterus and liver.|||Homodimer.|||Mutant animals result in lethality during prenatal development. Examination of the homozygous deficient embryos reveal subcutaneous edema, hemorrhages and defects in the vascular wall of subcutaneous capillaries. Hearts of deficient embryos show ventricular septal defects (VSDs) and thinner ventricular walls, as well as blood abnormalities. Analyses on protein expression and localization in endothelial cells of subcutaneous capillaries and endocardium show that the protein and caveolae with stomatal diaphragm were present in wild-type embryos, whereas the diaphragm is missing in the caveolae of deficient embryos. Deficient mice are viable after birth and survive up to 4 weeks on a mixed C57BL/6N/FVB-N background. Embryos on the mixed background show edema in neck and back, but no visible hemorrhages. Postnatal mutant mice display marked reduction in body size and kinked tails compare with wild-type, but no VSDs are observed in hearts. Detailed examination of the capillaries of kidneys and pancreas reveal that the knockout mice does not form fenestrae with diaphragm.|||caveola|||perinuclear region http://togogenome.org/gene/10090:Hephl1 ^@ http://purl.uniprot.org/uniprot/Q3V1H3 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the multicopper oxidase family.|||Binds 6 Cu cations per monomer.|||Defects in HEPHL1 are the cause of the curly whiskers phenotype (cw). Curly whiskers mice carry a recessive mutation that alters splicing and causes omission of exon 11 from the mature transcript. The cw phenotype is characterized by kinky, brittle vibrissae.|||HEPHL1 knockdown mice exhibit short and curled whiskers.|||Is a copper-binding glycoprotein with ferroxidase activity. It oxidizes Fe(2+) to Fe(3+) without releasing radical oxygen species. May be involved in the regulation of intracellular iron content.|||Membrane http://togogenome.org/gene/10090:Nr1d2 ^@ http://purl.uniprot.org/uniprot/Q4VAB7|||http://purl.uniprot.org/uniprot/Q60674|||http://purl.uniprot.org/uniprot/Q8C598 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by the CLOCK-BMAL1 heterodimer and DBP and repressed by CRY1.|||Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Binds DNA as a monomer or a homodimer (By similarity). Interacts with NCOA5 coactivator, leading to a strong increase of transcription of target genes (By similarity). Interacts (via N-terminus) with KAT5 (By similarity). Interacts (via C-terminus) with HDAC1 (By similarity). Interacts with ZNHIT1 (By similarity). Interacts with SIAH2 (By similarity).|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Deacetylated by HDAC1 (By similarity). Acetylation and deacetylation regulate its transcriptional regulatory activity (By similarity).|||Mice exhibit an altered circadian metabolism and feeding schedule, eating more and utilizing more carbohydrates as fuel during their nocturnal/sleep period (PubMed:29723273). Increased expression of circadian clock core genes and genes involved in lipid metabolism and fatty-acid oxidation in the skeletal muscle (PubMed:29723273). Mice exhibit decreased wakefulness and increased slow-wave sleep and rapid eye movement sleep during the dark phase (active period) (PubMed:29355503). Altered expression in the brain of core circadian clock genes and genes involved in sleep induction and wakefulness (PubMed:29355503). Conditional knockout of both NR1D1 and NR1D2 in bronchiolar epithelial cells abolished diurnal rhythmicity of PER2 in the bronchioles and increased inflammatory responses and chemokine activation (PubMed:29533925).|||Nucleus|||Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization.|||The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity.|||Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle. Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period (PubMed:29355503). Key regulator of skeletal muscle mitochondrial function; negatively regulates the skeletal muscle expression of core clock genes and genes involved in mitochondrial biogenesis, fatty acid beta-oxidation and lipid metabolism (PubMed:29723273). May play a role in the circadian control of neutrophilic inflammation in the lung (PubMed:29533925).|||Ubiquitinated by SIAH2; leading to its proteasomal degradation.|||Ubiquitous. Expressed abundantly in skeletal muscle and brown adipose tissue. Expressed during skeletal muscle myogenesis.|||Under more reducing intracellular redox conditions, Cys-381 is in its heme-bound state, which is optimal for recruitment of the NCOR1/HDAC3 corepressor complex and repression of target genes (By similarity). When subjected to oxidative stress conditions, Cys-381 undergoes oxidation to form a disulfide bridge with Cys-371, also triggering a ligand switch that results in release of bound heme and derepression of target genes (By similarity). http://togogenome.org/gene/10090:Pgp ^@ http://purl.uniprot.org/uniprot/Q8CHP8 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the HAD-like hydrolase superfamily. CbbY/CbbZ/Gph/YieH family.|||Binds 1 Mg(2+) ion per subunit.|||Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. Thereby, regulates the cellular levels of glycerol-3-phosphate a metabolic intermediate of glucose, lipid and energy metabolism (PubMed:26755581). Was also shown to have a 2-phosphoglycolate phosphatase activity and a tyrosine-protein phosphatase activity. However, their physiological relevance is unclear (PubMed:26755581, PubMed:24338473). In vitro, has also a phosphatase activity toward ADP, ATP, GDP and GTP (PubMed:24338473).|||Homodimer.|||Inhibited by orthovanadate, beryllium trifluoride, Ca(2+) and EDTA.|||Ubiquitously expressed with higher expression in testis, heart, skeletal muscle and islet tissue (at protein level).|||Up-regulated in white adipose tissue and down-regulated in brown adipose tissue upon fasting. http://togogenome.org/gene/10090:Mcm4 ^@ http://purl.uniprot.org/uniprot/P49717|||http://purl.uniprot.org/uniprot/Q3UA65|||http://purl.uniprot.org/uniprot/Q542F4 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Belongs to the MCM family.|||Chromosome|||Component of the MCM2-7 complex.|||Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:12207017). Interacts with MCMBP (By similarity).|||Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.|||Nucleus|||Sumoylated; SUMO2 modified in response to stress caused by inhibition of proteasome activity (in vitro). http://togogenome.org/gene/10090:Arhgef28 ^@ http://purl.uniprot.org/uniprot/P97433 ^@ Function|||Induction|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Functions also in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis.|||Highly enriched in the brain (at protein level). Also detected in lung and kidney.|||Homooligomer; forms some cytoplasmic aggregates. Forms a complex with MAPK8 and MAPK8IP1. Interacts with RHOA. Interacts with microtubules. Interacts with YWHAE and YWHAH. Interacts with PTK2/FAK1. Interacts with NEFL. Interacts with CTNND2; prevents interaction with RHOA.|||Phosphorylated on tyrosine upon stimulation of cells by laminin.|||Up-regulated in B-lymphocytes upon CD40 stimulation. Up-regulated by PTK2B/PYK2 (at protein level). http://togogenome.org/gene/10090:Apoc4 ^@ http://purl.uniprot.org/uniprot/Q61268 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the apolipoprotein C4 family.|||Expressed by the liver and secreted in plasma.|||May participate in lipoprotein metabolism.|||Secreted http://togogenome.org/gene/10090:Ghr ^@ http://purl.uniprot.org/uniprot/P16882|||http://purl.uniprot.org/uniprot/Q3UNY8|||http://purl.uniprot.org/uniprot/Q3UP14 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 1 subfamily.|||Cell membrane|||During gestation, both hepatic and serum expression begins at day 9. Levels increased 8-fold in liver and 30-fold in serum by late gestation. Levels of isoform 1 and isoform 2 similarly begin at day 9 with isoform 1 expression reaching maximum levels by day 13, isoform 2 levels continue to increase until the end of pregnancy.|||Expressed in all tissues tested including, liver, heart, adipose tissue, mammary gland, testes, ovary, brain, kidney and muscle. Highest levels in liver.|||On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2.|||On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation.|||On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization (By similarity).|||Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to, and activates the JAK2/STAT5 pathway (By similarity).|||Secreted|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).|||The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.|||The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization. http://togogenome.org/gene/10090:A130010J15Rik ^@ http://purl.uniprot.org/uniprot/Q9DAE8 ^@ Similarity ^@ Belongs to the UPF0739 family. http://togogenome.org/gene/10090:Vmn2r21 ^@ http://purl.uniprot.org/uniprot/K7N6Y7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Med18 ^@ http://purl.uniprot.org/uniprot/Q9CZ82 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 18 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Nthl1 ^@ http://purl.uniprot.org/uniprot/O35980 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nth/MutY family.|||Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines.|||Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand.|||Interacts with YBX1 (By similarity). Interacts with ERCC5/XPG; the interaction stimulates NTHL1 activity and NTHL1 binding to its DNA substrate (By similarity).|||Mitochondrion|||Nucleus|||Ubiquitinated by TRIM26; leading to proteasomal degradation.|||Widely expressed. http://togogenome.org/gene/10090:Kifc3 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLM0|||http://purl.uniprot.org/uniprot/E9PWU7|||http://purl.uniprot.org/uniprot/O35231 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Cytoplasmic vesicle membrane|||Interacts with annexin XIIIB.|||Minus-end microtubule-dependent motor protein. Involved in apically targeted transport. Required for zonula adherens maintenance.|||Predominant expression in the kidney, testis and ovary. Also expressed in brain, heart, liver, lung and uterus.|||adherens junction|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Mfsd12 ^@ http://purl.uniprot.org/uniprot/Q3U481 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Lysosome membrane|||Melanosome membrane|||Mice are darker and display a uniformly gray coat color, rather than the expected agouti coat color (PubMed:29025994). Coat color change is caused by a lack of pheomelanin, resulting in white, rather than yellow, banding of hairs (PubMed:29025994).|||Transporter that mediates the import of cysteine into melanosomes, thereby regulating skin/hair pigmentation (PubMed:33208952). In melanosomes, cysteine import is required both for normal levels of cystine, the oxidized dimer of cysteine, and provide cysteine for the production of the cysteinyldopas used in pheomelanin synthesis, thereby regulating skin/hair pigmentation (PubMed:33208952). Also catalyzes import of cysteine into lysosomes in non-pigmented cells (By similarity). http://togogenome.org/gene/10090:Pnck ^@ http://purl.uniprot.org/uniprot/Q3TYC1|||http://purl.uniprot.org/uniprot/Q3UYI0|||http://purl.uniprot.org/uniprot/Q9QYK9 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates CREB1 and SYN1/synapsin I. Phosphorylates and activates CAMK1 (By similarity).|||Cytoplasm|||During embryogenesis detected at 10 dpc and expression gradually increases thereafter. Expressed mainly in the nervous system, including brain, spinal cord, trigeminal ganglion, and retina. Within the CNS detected in the mantle zone, but not in the ventricular zone. Detected at postnatal day 23 with highest levels in mesencephalon. Also expressed in developing bone and gut.|||Expressed at highest levels in adult brain, and expressed in embryo. In the adult brain detected at high levels in the anterior olfactory nuclei, piriform cortex, septal nuclei, bed nuclei of the stria terminalis, hippocampal pyramidal cells, dentate granule cells, amygdala, hypothalamic nuclei, parabrachial nucleus, and nucleus of the solitary tract. Expressed at lower levels in adult ovary and heart and at very low levels in testis, lung and muscle.|||Nucleus http://togogenome.org/gene/10090:Abce1 ^@ http://purl.uniprot.org/uniprot/P61222 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ABC transporter superfamily. ABCE family.|||Cytoplasm|||Interacts with PINK1. Interacts with CNOT4. Interacts with PELO. Probably heterodimerizes with RNASEL; this interaction inhibits RNASEL.|||Mitochondrion|||Nucleoside-triphosphatase (NTPase) involved in ribosome recycling by mediating ribosome disassembly (By similarity). Able to hydrolyze ATP, GTP, UTP and CTP (By similarity). Splits ribosomes into free 60S subunits and tRNA- and mRNA-bound 40S subunits (By similarity). Acts either after canonical termination facilitated by release factors (ETF1/eRF1) or after recognition of stalled and vacant ribosomes by mRNA surveillance factors (PELO/Pelota) (By similarity). Involved in the No-Go Decay (NGD) pathway: recruited to stalled ribosomes by the Pelota-HBS1L complex, and drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway (By similarity). Also plays a role in quality control of translation of mitochondrial outer membrane-localized mRNA (By similarity). As part of the PINK1-regulated signaling, ubiquitinated by CNOT4 upon mitochondria damage; this modification generates polyubiquitin signals that recruit autophagy receptors to the mitochondrial outer membrane and initiate mitophagy (By similarity). RNASEL-specific protein inhibitor which antagonizes the binding of 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) to RNASEL (PubMed:10866653). Negative regulator of the anti-viral effect of the interferon-regulated 2-5A/RNASEL pathway (By similarity).|||Ubiquitinated by CNOT4 (By similarity). Ubiquitination mediates the recruitment of autophagy receptors to the mitochondrial outer membrane and initiates mitophagy (By similarity). http://togogenome.org/gene/10090:Nxpe3 ^@ http://purl.uniprot.org/uniprot/B9EKK6 ^@ Similarity ^@ Belongs to the NXPE family. http://togogenome.org/gene/10090:Ldhd ^@ http://purl.uniprot.org/uniprot/Q7TNG8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAD-binding oxidoreductase/transferase type 4 family.|||Interacts with CSRP3.|||Involved in D-lactate, but not L-lactate catabolic process.|||Mitochondrion|||Readily detected in liver and kidney, with a weaker signal observed in heart, skeletal muscle, stomach, brain, and lung. http://togogenome.org/gene/10090:Plin5 ^@ http://purl.uniprot.org/uniprot/Q8BVZ1 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the perilipin family.|||Cytoplasm|||Highly expressed in oxidative tissues, including heart, liver, brown adipose tissue (BAT) and slow-twitch fibers of skeletal muscle. Lower expression in epididymal white adipose tissue and anterior tibialis and quadriceps. Expressed in adrenal glands. Isoform 2 has the highest expression in heart.|||Homooligomer. Interacts with PNPLA2; prevents interaction of PNPLA2 with ABHD5. Interacts with ABHD5; targets ABHD5 to lipid droplets and promotes interaction of ABHD5 with PNPLA2. Interacts with LIPE.|||Lipid droplet|||Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE.|||Mitochondrion|||No visible phenotype. Mice lack detectable lipid droplets in heart. The triacylglycerol and fatty acid content in heart is lower.|||Phosphorylated by PKA. Phosphorylated on serine in skeletal muscle at rest or with lipolytic stimulation.|||Up-regulated by fasting, PPARD, PPARA and PLIN4. Increased in muscle of high-fat diet fed mice. Induced by unsaturated long chain fatty acid in muscle. http://togogenome.org/gene/10090:Adora1 ^@ http://purl.uniprot.org/uniprot/Q3UYG0|||http://purl.uniprot.org/uniprot/Q60612|||http://purl.uniprot.org/uniprot/Q6AXD8|||http://purl.uniprot.org/uniprot/Q8CAH1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. http://togogenome.org/gene/10090:Tcim ^@ http://purl.uniprot.org/uniprot/Q9D915 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in liver, expression levels decrease in regenerating liver (PubMed:25985737). In bone marrow, expressed in large progenitor-like cells, cells with ring-shaped nuclei and, at lower, levels in hematopietic stem cell-like cells with round nuclei (at protein level) (PubMed:24937306).|||Mice have increased number of myeloid and lymphoid cells on peripheral blood compared to wild type controls. Red blood cells are small-sized but increased in number. In bone marrow, cells show higher colony forming units.|||Monomer. Interacts with NOTCH2 (via ANK repeats), the interaction inhibits the nuclear translocation of NOTCH2 N2ICD. Interacts (C-terminus) with CBY1 (C-terminus), TCIM competes with CTNNB1 for the interaction with CBY1.|||Nucleus|||Nucleus speckle|||Seems to be involved in the regulation of cell growth an differentiation, may play different and opposite roles depending on the tissue or cell type. May enhance the WNT-CTNNB1 pathway by relieving antagonistic activity of CBY1. Enhances the proliferation of follicular dendritic cells. Plays a role in the mitogen-activated MAPK2/3 signaling pathway, positively regulates G1-to-S-phase transition of the cell cycle. In endothelial cells, enhances key inflammatory mediators and inflammatory response through the modulation of NF-kappaB transcriptional regulatory activity. Involved in the regulation of heat shock response, seems to play a positive feedback with HSF1 to modulate heat-shock downstream gene expression (By similarity). Plays a role in the regulation of hematopoiesis even if the mechanisms are unknown (PubMed:24937306). In cancers such as thyroid or lung cancer, it has been described as promoter of cell proliferation, G1-to-S-phase transition and inhibitor of apoptosis. However, it negatively regulates self-renewal of liver cancer cells via suppresion of NOTCH2 signaling (By similarity).|||nucleolus http://togogenome.org/gene/10090:1700009N14Rik ^@ http://purl.uniprot.org/uniprot/Q14AA6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Ran family.|||GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle.|||Nucleus http://togogenome.org/gene/10090:Lmntd1 ^@ http://purl.uniprot.org/uniprot/Q9D4C1 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Eml3 ^@ http://purl.uniprot.org/uniprot/Q8VC03 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat EMAP family.|||Cytoplasm|||Homotrimer; self-association is mediated by the N-terminal coiled coil (By similarity). Interacts with EML2 but not with EML1 (By similarity). Interacts (phosphorylated at Thr-882) with TUBG1, HAUS1, HAUS2, HAUS3, HAUS4, HAUS5, HAUS6, HAUS7 and HAUS8.|||Midbody|||Nucleus|||Phosphorylation at Thr-882 during mitosis is required for interaction with TUBG1, HAUS1, HAUS2, HAUS3, HAUS4, HAUS5, HAUS6, HAUS7 and HAUS8 and their recruitment to spindle microtubules.|||Regulates mitotic spindle assembly, microtubule (MT)-kinetochore attachment and chromosome separation via recruitment of HAUS augmin-like complex and TUBG1 to the existing MTs and promoting MT-based MT nucleation (By similarity). Required for proper alignnment of chromosomes during metaphase (By similarity).|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Slc6a3 ^@ http://purl.uniprot.org/uniprot/Q61327 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A3 subfamily.|||Cell membrane|||Found in the substantia nigra and ventral tegmental dopamine neurons, in fibers of the medial forebrain bundle ascending into the striatum, and within dense fiber networks and varicosities in the dorsal and ventral striatum (at protein level) (PubMed:19357284, PubMed:17296554). Lower expression in the cortex (at protein level) (PubMed:19357284). Absent from the corpus callosum (PubMed:19357284). Expressed throughout the retina at postnatal day 8 (PubMed:30936473).|||Homooligomer; disulfide-linked (By similarity). Interacts with PRKCABP and TGFB1I1 (PubMed:12177201). Interacts (via N-terminus) with SYNGR3 (via N-terminus) (PubMed:19357284). Interacts with SLC18A2 (PubMed:19357284). Interacts with TOR1A (ATP-bound); TOR1A regulates SLC6A3 subcellular location. Interacts with alpha-synuclein/SNCA (By similarity). Interacts with SEPTIN4 (PubMed:17296554).|||Inhibited by amphetamine, bupropion, cocaine and ritalin.|||Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:12606774). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (PubMed:30936473).|||This protein is the target of psychomotor stimulants such as amphetamines and cocaine.|||axon|||neuron projection http://togogenome.org/gene/10090:Cdhr5 ^@ http://purl.uniprot.org/uniprot/Q8VHF2 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Detected at embryonic day 7. Expression decreases by day 11 and increases again between embryonic days 15 and 17.|||Intermicrovillar adhesion molecule that forms, via its extracellular domain, calcium-dependent heterophilic complexes with CDHR2 on adjacent microvilli. Thereby, controls the packing of microvilli at the apical membrane of epithelial cells. Through its cytoplasmic domain, interacts with microvillus cytoplasmic proteins to form the intermicrovillar adhesion complex/IMAC. This complex plays a central role in microvilli and epithelial brush border differentiation.|||N- and O-glycosylated.|||Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5. Interacts (via cytoplasmic domain) with USH1C and MYO7B; required for proper localization of CDHR5 to microvilli tips and its function in brush border differentiation.|||microvillus membrane http://togogenome.org/gene/10090:Pwp1 ^@ http://purl.uniprot.org/uniprot/Q99LL5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the RNA polymerase (Pol I) complex. Interacts with POLR1E.|||Belongs to the WD repeat PWP1 family.|||Chromatin-associated factor that regulates transcription (By similarity). Regulates Pol I-mediated rRNA biogenesis and, probably, Pol III-mediated transcription (By similarity). Regulates the epigenetic status of rDNA (By similarity).|||Chromosome|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Mfsd5 ^@ http://purl.uniprot.org/uniprot/Q921Y4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Cell membrane|||Mediates high-affinity intracellular uptake of the rare oligo-element molybdenum. http://togogenome.org/gene/10090:Il20ra ^@ http://purl.uniprot.org/uniprot/Q6PHB0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II cytokine receptor family.|||Heterodimer with IL20RB and heterodimer with IL10RB.|||Membrane|||The IL20RA/IL20RB dimer is a receptor for IL19, IL20 and IL24. The IL20RA/IL10RB dimer is a receptor for IL26 (By similarity). http://togogenome.org/gene/10090:Shld2 ^@ http://purl.uniprot.org/uniprot/Q3UEN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SHLD2 family.|||Chromosome|||Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7. Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus. Interacts with TP53BP1. Interacts with RIF1.|||Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres. http://togogenome.org/gene/10090:Or4p7 ^@ http://purl.uniprot.org/uniprot/Q7TR20 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hyal6 ^@ http://purl.uniprot.org/uniprot/Q9D4E9 ^@ Similarity ^@ Belongs to the glycosyl hydrolase 56 family. http://togogenome.org/gene/10090:Ch25h ^@ http://purl.uniprot.org/uniprot/Q9Z0F5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sterol desaturase family.|||Catalyzes the formation of 25-hydroxycholesterol from cholesterol, leading to repress cholesterol biosynthetic enzymes (PubMed:9852097, PubMed:29033131). Plays a key role in cell positioning and movement in lymphoid tissues: 25-hydroxycholesterol is an intermediate in biosynthesis of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC), an oxysterol that acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells (PubMed:22999953). May play an important role in regulating lipid metabolism by synthesizing a corepressor that blocks sterol regulatory element binding protein (SREBP) processing (PubMed:9852097). In testis, production of 25-hydroxycholesterol by macrophages may play a role in Leydig cell differentiation (PubMed:9852097). Required to restrain inflammation in macrophages: production of 25-hydroxycholesterol protects macrophages from cholesterol overload, thereby preventing mitochondrial DNA release and subsequent activation of the AIM2 inflammasome (PubMed:29033131). Interferon-stimulated gene which has broad antiviral activities against a wide range of enveloped viruses (By similarity).|||Endoplasmic reticulum membrane|||Mice do not display any apparent alteration in bile acid synthesis and cholesterol metabolism (PubMed:12543708). Macrophages however display impaired mitochondrial metabolism, due to increased cholesterol that triggers cytosolic mitochondrial DNA release and subsequent activation of the AIM2 inflammasome (PubMed:29033131).|||N-glycosylated.|||Widely expressed at low level and at higher level in the lung. Weakly expressed in the heart, lung and kidney. http://togogenome.org/gene/10090:Plcb4 ^@ http://purl.uniprot.org/uniprot/Q91UZ1 ^@ Cofactor|||Function ^@ Binds 1 Ca(2+) ion per subunit.|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. http://togogenome.org/gene/10090:Rell1 ^@ http://purl.uniprot.org/uniprot/Q8K2J7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RELT family.|||Cell membrane|||Induces activation of MAPK14/p38 cascade, when overexpressed. Induces apoptosis, when overexpressed.|||Interacts with RELT, RELL2, OXSR1 and PLSCR1. http://togogenome.org/gene/10090:Skint4 ^@ http://purl.uniprot.org/uniprot/A7TZF3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin, thymus and, to a lower extent, bladder and testis.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Klf15 ^@ http://purl.uniprot.org/uniprot/Q9EPW2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Expressed in aortic smooth muscle cells.|||In the heart, up-regulated by the CLOCK/BMAL1 heterodimer. In podocytes, up-regulated by retinoic acid.|||Interacts with MYOCD. Interacts with EP300 (By similarity).|||KLF15 null mice are viable, but in response to pressure overload, they develop cardiac hypertrophy and fibrosis.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional regulator that binds to the GA element of the CLCNKA promoter (By similarity). Binds to the KCNIP2 promoter and regulates KCNIP2 circadian expression in the heart. Is a repressor of CCN2 expression, involved in the control of cardiac fibrosis. Is also involved in the control of cardiac hypertrophy acting through the inhibition of MEF2A, GATA4 and MYOCD activity. Is a negative regulator of TP53 acetylation. Inhibits NF-kappa-B activation through repression of EP300-dependent RELA acetylation (By similarity). Involved in podocyte differentiation. http://togogenome.org/gene/10090:Adipor2 ^@ http://purl.uniprot.org/uniprot/Q53YY3|||http://purl.uniprot.org/uniprot/Q8BQS5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ADIPOR family.|||Cell membrane|||Detected in liver and quadriceps muscle (at protein level) (PubMed:17327425). Highly expressed in liver (PubMed:12802337). Highly expressed in white adipose tissue, and at intermediate levels in brown adipose tissue (PubMed:24742672). Expressed at intermediate level in heart, kidney, lung and skeletal muscle. Weakly expressed in brain, spleen and testis.|||May form homooligomers and heterooligomers with ADIPOR1 (By similarity). Interacts with APPL2 (via BAR domain); ADIPOQ dissociates this interaction (PubMed:19661063).|||Membrane|||Mutant mice are viable and fertile, and display increased glucose tolerance (PubMed:17327425, PubMed:17068142, PubMed:17268472, PubMed:24742672). On a high fat diet, they have lower fasting insulin levels than wild-type (PubMed:17327425, PubMed:24742672). Mutant mice have lower plasma cholesterol levels on a high fat diet, and possibly also on normal chow (PubMed:17327425, PubMed:17068142). The precise phenotype may depend on the experimental details and on genotype. Male and female mutant mice are somewhat leaner than wild-type on standard chow and do not display increased weight gain on a high fat diet (PubMed:17327425, PubMed:24742672). Mutant mice have normal body weight on standard chow, but decreased weight gain on a high-fat diet (PubMed:17068142). Female mutant mice display lower total body fat than wild-type on a high fat diet (PubMed:17327425). Both male and female mice have reduced levels of white and brown adipose tissue relative to wild-type (PubMed:17327425). Mutant male mice display decreased testis weight, atrophy of the seminiferous tubules and aspermia (PubMed:17327425). Both male and female mice display increased brain weight relative to wild-type (PubMed:17327425). Mutant mice have increased locomotor activity and increased energy expenditure on a high fat diet (PubMed:17327425). Mutant mice display impaired revascularization, limb retraction, atrophy and necrosis in response to limb ischemia caused by severing the femoral artery (PubMed:24742672). Hepatocytes from mice lacking both Adipor1 and Adipor2 show loss of adiponectin binding and lack of adiponectin-mediated activation of AMPK and Ppara (PubMed:17268472). Mice lacking both Adipor1 and Adipor2 display elevated glucose and insulin levels in blood plasma, indicative of glucose intolerance and insulin resistance (PubMed:17268472).|||Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:17327425, PubMed:17068142, PubMed:17268472, PubMed:24742672). Required for normal body fat and glucose homeostasis (PubMed:17327425, PubMed:17068142, PubMed:17268472, PubMed:24742672). ADIPOQ-binding activates a signaling cascade that leads to increased PPARA activity, and ultimately to increased fatty acid oxidation and glucose uptake (PubMed:12802337, PubMed:17268472, PubMed:24742672). Has intermediate affinity for globular and full-length adiponectin (PubMed:12802337). Required for normal revascularization after chronic ischemia caused by severing of blood vessels (PubMed:24742672).|||The N-terminus is cytoplasmic and the C-terminus is extracellular, contrary to what is observed for G-protein coupled receptors. Unlike G-protein coupled receptors, transmembrane helices are not kinked or tilted relative to the plane of the membrane. http://togogenome.org/gene/10090:Stk32b ^@ http://purl.uniprot.org/uniprot/Q9JJX8 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Tecpr1 ^@ http://purl.uniprot.org/uniprot/Q80VP0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TECPR1 family.|||Interacts with ATG5; the interaction is direct. Interacts with WIPI2. Interacts with the ATG5-ATG12 conjugate, the interaction is however mutually exclusive with ATG16, since it does not interact with ATG12-ATG5-ATG16 complex.|||Lysosome membrane|||Tethering factor involved in autophagy. Involved in autophagosome maturation by promoting the autophagosome fusion with lysosomes: acts by associating with both the ATG5-ATG12 conjugate and phosphatidylinositol-3-phosphate (PtdIns(3)P) present at the surface of autophagosomes. Also involved in selective autophagy against bacterial pathogens, by being required for phagophore/preautophagosomal structure biogenesis and maturation (By similarity).|||The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns(3)P).|||autophagosome membrane http://togogenome.org/gene/10090:Adat1 ^@ http://purl.uniprot.org/uniprot/Q9JHI2 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the ADAT1 family.|||Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.|||Specifically deaminates adenosine-37 to inosine in tRNA-Ala. http://togogenome.org/gene/10090:Drg1 ^@ http://purl.uniprot.org/uniprot/P32233 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.|||Catalyzes the conversion of GTP to GDP through hydrolysis of the gamma-phosphate bond in GTP. Appears to have an intrinsic GTPase activity that is stimulated by ZC3H15/DFRP1 binding likely by increasing the affinity for the potassium ions. When hydroxylated at C-3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation. Binds to microtubules and promotes microtubule polymerization and bundling that are required for mitotic spindle assembly during prophase to anaphase transition. GTPase activity is not necessary for these microtubule-related functions.|||Cytoplasm|||Fairly high levels in liver, heart, kidney, testis and brain. Very low levels in lung, spleen, and skeletal muscle.|||Hydroxylated (with S stereochemistry) at C-3 of Lys-22 by JMJD7.|||Interacts (via its C-terminal) with TAL1 (By similarity). Interacts with DFRP1/ZC3H15; this interaction prevents DRG1 poly-ubiquitination and degradation by proteasome. DRG1-DFRP1/ZC3H15 complex co-sediments with polysomes (By similarity) (PubMed:15676025). Interacts with STK16. Interacts with JMJD7 (By similarity).|||Its C-terminal domain interacts with TAL1.|||Nucleus|||Phosphorylated at Thr-100 by STK16.|||Polyubiquitinated; this modification induces proteolytic degradation and is impaired by interaction with ZC3H15.|||Predominantly expressed in the embryo and down-regulated during development.|||Sumoylated by UBE2I in response to MEKK1-mediated stimuli.|||The GTPase activity is enhanced by potassium ions as well as by DFRP1 binding.|||The ThrRS, GTPase, SpoT (TGS) domain is not necessary for GTP binding nor for the GTPase activity. It appears to play a regulatory role favoring GTP hydrolysis mediated by DFRP1/ZC3H15. http://togogenome.org/gene/10090:Anapc13 ^@ http://purl.uniprot.org/uniprot/Q8R034 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APC13 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Nucleus|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. http://togogenome.org/gene/10090:Plch2 ^@ http://purl.uniprot.org/uniprot/A2AP18 ^@ Activity Regulation|||Developmental Stage|||Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Aberrant splicing.|||Activity is stimulated by GNB1:GNG2.|||Cell membrane|||Cytoplasm|||Expressed at 2 weeks after birth but barely detected 1 week after birth. Increased expression during brain development.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Specifically detected in the brain, with higher level in cerebral cortex, olfactory bulb and hippocampus (at protein level). Expressed in the pyramidal cells of the hippocampus, but also in eye and lung.|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. This phospholipase activity is very sensitive to calcium. May be important for formation and maintenance of the neuronal network in the postnatal brain. http://togogenome.org/gene/10090:Klra8 ^@ http://purl.uniprot.org/uniprot/Q3UPS5|||http://purl.uniprot.org/uniprot/Q60682 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Homodimer; disulfide-linked. Interacts with the adapter protein TYROBP/DAP12; the interaction leads to natural killer cell activation (PubMed:9647200).|||Membrane|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Myo1b ^@ http://purl.uniprot.org/uniprot/E9QNH6|||http://purl.uniprot.org/uniprot/P46735|||http://purl.uniprot.org/uniprot/Q3TTZ3|||http://purl.uniprot.org/uniprot/Q7TQD7 ^@ Caution|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Motor protein that may participate in process critical to neuronal development and function such as cell migration, neurite outgrowth and vesicular transport.|||Prominent expression is seen in the brain, lung and liver. It is also expressed in the heart and testis. A high level expression is seen in virtually all neurons (but not glia) in the postnatal and adult mouse brain and in neuroblasts of the cerebellar external granular layer.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1). http://togogenome.org/gene/10090:Col5a2 ^@ http://purl.uniprot.org/uniprot/Q3U962 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibrillar collagen family.|||Expressed in embryos from 9 days of gestation onward. In 12.5 dpc embryos, low and diffuse level of expression was observed in the peritoneal membranes and intestinal and craniofacial mesenchymes. By 16.5 dpc, expression is higher and exhibits a more restricted accumulation in primary ossified regions, perichondrium, joints, tendon, atrioventricular valve of heart, and in selected portions of the head.|||Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.|||Mice homozygous for the targeted deletion of the N-terminal telopeptide segment of the COL5A2 chain show poor survival rates, possibly because of complications from spinal deformities, and exhibit skin and eye abnormalities caused by disorganized type I collagen fibrils.|||Prolines at the third position of the tripeptide repeating unit (G-X-P) are hydroxylated in some or all of the chains. Probably 3-hydroxylated on prolines by LEPREL1.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||The alpha 1(V)-alpha 1(V)-alpha 2(V) heterotrimer makes a critical contribution to fibrillogenesis, basement membrane organization, and cell viability, and may play a possible role in the development of a functional skin matrix.|||Trimers of two alpha 1(V) and one alpha 2(V) chains expressed in most tissues and trimers of one alpha 1(V), one alpha 2(V), and one alpha 3(V) chains with a more limited distribution of expression.|||Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin. Type V collagen is a key determinant in the assembly of tissue-specific matrices.|||extracellular matrix http://togogenome.org/gene/10090:Pdcd4 ^@ http://purl.uniprot.org/uniprot/Q61823 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDCD4 family.|||Binds EIF4A1 via both MI domains.|||Cytoplasm|||Decreases benign tumor development and malignant progression.|||Expressed ubiquitously. Highyly expressed in thymus and liver. Moderately expressed in brain, kidney and spleen; weakly in lung and heart. Expression is up- or down-regulated in response to apoptosis inducers. Regulated by many programmed cell death-inducing stimuli.|||Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA.|||Interacts (via MI domains) with EIF4A1 and EIF4A2 (via N-terminal domain). Heterotrimer with EIF4A1; one molecule of PDCD4 binds two molecules of EIF4A1. Interacts with EIF4G1. May form a complex with EIF4A1 and EIF4G1. The interaction between PDCD4 and EIF4A1 interferes with the interaction between EIF4A1 and EIF4G. When phosphorylated, interacts with BTRC and FBXW11 (By similarity).|||Nucleus|||Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4.|||Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Pglyrp2 ^@ http://purl.uniprot.org/uniprot/A0A498WFR9|||http://purl.uniprot.org/uniprot/Q8VCS0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.|||May play a scavenger role by digesting biologically active peptidoglycan (PGN) into biologically inactive fragments. Has no direct bacteriolytic activity.|||Membrane|||Secreted|||Strongly expressed in liver and fetal liver. http://togogenome.org/gene/10090:Kcnj3 ^@ http://purl.uniprot.org/uniprot/B1AYE4|||http://purl.uniprot.org/uniprot/P63250|||http://purl.uniprot.org/uniprot/Q3ZAT1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein activated heteromultimer pore-forming unit. The resulting inward current is much larger (By similarity).|||Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein activated heteromultimer pore-forming unit. The resulting inward current is much larger.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ3 subfamily.|||Membrane|||This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This receptor plays a crucial role in regulating the heartbeat. http://togogenome.org/gene/10090:Scube3 ^@ http://purl.uniprot.org/uniprot/A0A3B2WCG9|||http://purl.uniprot.org/uniprot/Q66PY1 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell surface|||Forms homooligomers. Forms heterooligomers with SCUBE1 and SCUBE2. Interacts with TGFBR2 through the CUB domain; this interaction does not affect TGFB1-binding to TGFBR2. Interacts with BMP2, BMP4 and BMP7; the interaction is mediated by the CUB domain. Interacts with BMPR1A, BMPR1B and BMPR2; the interaction with BMPR1A and BMPR1B is BMP2- and BMP4-dependent.|||Highly expressed in femur and humerus with little or no expression in non-bone tissues.|||Is a positive regulator of the BMP signaling pathway, required for proper chondrogenesis, osteogenesis and skeletal development (PubMed:33308444). It acts as coreceptor for BMP ligands, particularly BMP2 and BMP4, facilitating their interactions with BMP type I receptors (By similarity). It is required for ligand-induced recruitment of BMP receptors to lipid rafts (PubMed:33308444). Binds to TGFBR2 and activates TGFB signaling (By similarity).|||Knockout mice are viable and do not show any macroscopically visible abnormality at birth. At day P1, however, knockout mice are shorter than their control littermates, and show misaligned upper/lower incisors and altered craniofacial development. All appendicular (forelimbs and hindlimbs) and axial (skull, vertebral column, and rib cage) skeletal elements are smaller than in control animals. The defective skeletal growth persists up to adulthood.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Proteolytic cleavage produces a CUB-containing C-terminal fragment that retains the ability to bind to TGFBR2. This reaction is catalyzed in vitro by MMP2 and, to a lesser extent, by MMP9 (By similarity).|||Secreted http://togogenome.org/gene/10090:Cldn4 ^@ http://purl.uniprot.org/uniprot/O35054|||http://purl.uniprot.org/uniprot/Q3UM35 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Cell membrane|||Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney (PubMed:20921420). Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts (PubMed:20921420). Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||Expressed primarily in lung and kidney (PubMed:9892664). Present in both cortical and medullar collecting ducts (at protein level) (PubMed:20921420).|||Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions (By similarity). Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3 (PubMed:10601346, PubMed:16236711). Interacts with CLDN1 (By similarity). Interacts with CLDN8 (PubMed:20921420).|||Membrane|||Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1 (By similarity).|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Tmem258 ^@ http://purl.uniprot.org/uniprot/E9Q853|||http://purl.uniprot.org/uniprot/P61166|||http://purl.uniprot.org/uniprot/Q60FD1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OST5 family.|||Component of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (Probable). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity).|||Component of the oligosaccharyltransferase (OST) complex.|||Cytoplasm|||Endoplasmic reticulum|||Membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (By similarity). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. Involved in ER homeostasis in the colonic epithelium.|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. http://togogenome.org/gene/10090:Efna4 ^@ http://purl.uniprot.org/uniprot/O08542|||http://purl.uniprot.org/uniprot/Q3UQB5|||http://purl.uniprot.org/uniprot/Q9CZS8 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ephrin family.|||Cell membrane|||Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. May play a role in the interaction between activated B-lymphocytes and dendritic cells in tonsils (By similarity).|||Expressed in myogenic progenitor cells.|||In myogenic progenitor cells, highly expressed at 11.5 dpc and ceases its expression at the late fetal stage (17.5 dpc).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Zbtb45 ^@ http://purl.uniprot.org/uniprot/Q52KG4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Detected in embryonic forebrain at stages 12.5 dpc and 14.5 dpc where it is ubiquitously expressed.|||May be involved in transcriptional regulation (Probable). In the central nervous system, may play a role in glial cell differentiation (PubMed:21131782).|||Nucleus http://togogenome.org/gene/10090:Or51g1 ^@ http://purl.uniprot.org/uniprot/Q8VH17 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:G3bp1 ^@ http://purl.uniprot.org/uniprot/P97855 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arg-435 is dimethylated, probably to asymmetric dimethylarginine.|||Can mediate both protein-protein and protein-RNA interactions via the NTF2 domain and RNA-binding domain RRM; protein-protein and protein-RNA interactions are essential for undergoing liquid-liquid phase separation (LLPS).|||Homodimer and oligomer (By similarity). Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP1 (PubMed:15086518). Binds to the SH3 domain of Ras GTPase-activating protein (RASA1) in proliferating cells (PubMed:8649363). No interaction in quiescent cells (PubMed:8649363). Interacts (via NTF2 domain) with USP10; inhibiting stress granule formation by lowering G3BP1 valence (By similarity). Interacts (via NTF2 domain) with CAPRIN1; promoting stress granule formation by lowering the saturation-concentration of G3BP1 (By similarity). Interacts (via NTF2 domain) with UBAP2L; promoting stress granule formation (By similarity). Associates (via RG-rich region) with 40S ribosome subunits (By similarity). Interacts with RPTOR and SPAG5; this complex is increased by oxidative stress (By similarity). Interacts with ATXN2L (By similarity). Interacts with STYXL1 (By similarity). Interacts with CGAS (via N-terminus); this interaction promotes the DNA-binding and activation of CGAS (By similarity). Interacts (via C-terminus) with RIGI (By similarity). Interacts with PABPC1 (By similarity). Interacts with QKI (isoforms QKI6 and QKI7); directing N(7)-methylguanine-containing mRNAs to stress granules (By similarity).|||Mg(2+) is required for helicase activity.|||Nucleus|||Perikaryon|||Phosphorylation of the acidic disordered region regulates stress granule assembly. RASA1-dependent phosphorylation of Ser-149 induces a conformational change that prevents self-association. Dephosphorylation after HRAS activation is required for stress granule assembly. Ser-149 phosphorylation induces partial nuclear localization.|||Protein involved in various processes, such as stress granule formation and innate immunity (By similarity). Plays an essential role in stress granule formation (By similarity). Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress (By similarity). Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations (By similarity). Also acts as an ATP- and magnesium-dependent helicase: unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency (By similarity). Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA (By similarity). Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends (By similarity). Plays an essential role in innate immunity by promoting CGAS and RIGI activity (By similarity). Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS (By similarity). Triggers the condensation of cGAS, a process probably linked to the formation of membrane-less organelles. Enhances also RIGI-induced type I interferon production probably by helping RIGI at sensing pathogenic RNA (By similarity). May also act as a phosphorylation-dependent sequence-specific endoribonuclease in vitro: Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510).|||Stress granule|||The NTF2 domain mediates interaction with CAPRIN1 and USP10 regulators, thereby regulating assembly of stress granules.|||The acidic disordered region acts as a negative regulator of phase separation.|||Ubiquitinated by TRIM21 via 'Lys-63'-linked polyubiquitination in the NTF2 domain in response to heat shock, leading to stress granule disassembly: ubiquitination promotes interaction with the FAF2 adapter, followed by interaction with VCP, which extracts G3BP1 from stress granules, leading to stress granule disassembly. In case of prolonged stress, ubiquitination by TRIM21 leads to autophagy-dependent degradation of G3BP1 via recruitment of ubiquitinated G3BP1 by SQSTM1 and/or CALCOCO2 to autophagosomes.|||Ubiquitous.|||Under physiological conditions, G3BP1 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation. Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state. Binding of unfolded mRNA to G3BP1 outcompetes the intramolecular interactions and RNA-bound G3BP1 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS).|||cytosol http://togogenome.org/gene/10090:Stoml2 ^@ http://purl.uniprot.org/uniprot/Q99JB2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the band 7/mec-2 family.|||Cell membrane|||Embryonic lethal at the preimplantation stage. T-cell-specific conditional knockout does not alter the normal development of those cells but decreases their responses to stimulation through the T-cell receptor.|||Forms homooligomers (By similarity). Interacts with MFN2; may form heterooligomers (By similarity). Interacts with PHB1 and PHB2; recruits them to cardiolipin-enriched mitochondrial membranes and stabilizes them (By similarity). Interacts with CACNA2D2.|||Membrane raft|||Mitochondrial protein that probably regulates the biogenesis and the activity of mitochondria. Stimulates cardiolipin biosynthesis, binds cardiolipin-enriched membranes where it recruits and stabilizes some proteins including prohibitin and may therefore act in the organization of functional microdomains in mitochondrial membranes. Through regulation of the mitochondrial function may play a role into several biological processes including cell migration, cell proliferation, T-cell activation, calcium homeostasis and cellular response to stress. May play a role in calcium homeostasis through negative regulation of calcium efflux from mitochondria. Required for mitochondrial hyperfusion a pro-survival cellular response to stress which results in increased ATP production by mitochondria. May also regulate the organization of functional domains at the plasma membrane and play a role in T-cell activation through association with the T-cell receptor signaling complex and its regulation.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||cytoskeleton http://togogenome.org/gene/10090:Gucy1b1 ^@ http://purl.uniprot.org/uniprot/O54865|||http://purl.uniprot.org/uniprot/Q3UTI4|||http://purl.uniprot.org/uniprot/Q80YP4 ^@ Activity Regulation|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by nitric oxide in the presence of magnesium or manganese ions.|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 1 or 2 heme groups per heterodimer. Heme is required for responding to nitric oxide, but not for catalytic activity.|||Cytoplasm|||Mediates responses to nitric oxide (NO) by catalyzing the biosynthesis of the signaling molecule cGMP.|||The active enzyme is formed by a heterodimer of an alpha and a beta subunit. Heterodimer with GUCY1A1. Can also form inactive homodimers in vitro.|||There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. http://togogenome.org/gene/10090:Lhcgr ^@ http://purl.uniprot.org/uniprot/P30730 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.|||Cell membrane|||Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.|||Sulfated. http://togogenome.org/gene/10090:Bsph1 ^@ http://purl.uniprot.org/uniprot/B7ZWD1|||http://purl.uniprot.org/uniprot/Q3UW26 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the seminal plasma protein family.|||Binds sperm in vitro and promotes sperm capacitation (PubMed:22539676, PubMed:24307707). Specifically promotes capacitation induced by high density lipoproteins (HDLs) (PubMed:25602034). Also binds heparin, phospholipid liposomes, and weakly to gelatin (PubMed:22539676). Does not bind chondroitin sulfate B (PubMed:22539676).|||Expressed only in the epididymis.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Ldb2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFS7|||http://purl.uniprot.org/uniprot/O55203 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LDB family.|||Expressed in multiple tissues including heart, brain, liver, kidney, testis, lung and muscle, with expression highest in the brain, trigeminal ganglia, and lung.|||Expression in the embryo overlaps that of LIM domain-containing proteins (PubMed:9192866). Expressed widely in the embryo with highest expression in several regions of the brain, and the central nervous system ganglia (PubMed:9192866).|||Interacts with LHX9 (PubMed:10330499). Interacts with SLK; leading to negatively regulate SLK kinase activity (PubMed:19675209). Interacts with LMO4 (PubMed:9860983).|||Interacts with PITX1 (PubMed:9192866). Interacts with LHX3 (PubMed:9192866).|||Lacks LIM-binding domain.|||Nucleus|||Regulates the transcriptional activity of LIM-containing proteins such as LHX3 or PITX1.|||Transcription cofactor (PubMed:9192866). Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors (PubMed:9192866).|||Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Dusp8 ^@ http://purl.uniprot.org/uniprot/O09112|||http://purl.uniprot.org/uniprot/Q7TSZ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Expressed predominantly in brain and lung.|||Has phosphatase activity with synthetic phosphatase substrates and negatively regulates mitogen-activated protein kinase activity, presumably by catalysing their dephosphorylation (PubMed:7561881). Expected to display protein phosphatase activity toward phosphotyrosine, phosphoserine and phosphothreonine residues (Probable).|||Monomer.|||Nucleus http://togogenome.org/gene/10090:4933427D14Rik ^@ http://purl.uniprot.org/uniprot/Q6A000 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CEP63 and WDR62 (By similarity). Forms a complex with OFD1 and CEP20/FOR20 (PubMed:26643951). Interacts with PCM1 (PubMed:26643951).|||Involved in centriole duplication. Positively regulates CEP63 centrosomal localization. Required for WDR62 centrosomal localization and promotes the centrosomal localization of CDK2. May play a role in cilium assembly.|||centriolar satellite http://togogenome.org/gene/10090:Lcp2 ^@ http://purl.uniprot.org/uniprot/Q60787 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in spleen, thymus, and peripheral blood leukocytes.|||Interacts with SHB. Interacts with PRAM1 (By similarity). Interacts with SLA (PubMed:10662792). Interacts with GRB2 (PubMed:7706237). Interacts with CBLB (PubMed:10646608). Interacts (via SH2 domain) with CD6 (via tyrosine phosphorylated C-terminus) (PubMed:16914752, PubMed:24584089). Interacts with FYB1 and the phosphorylated form of FYB2 (By similarity).|||Involved in T-cell antigen receptor mediated signaling.|||Phosphorylated after T-cell receptor activation by ZAP70, ITK and TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2. SYK-dependent phosphorylation is required for recruitment of PI3K signaling components (By similarity).|||The SH2 domain mediates interaction with SHB. http://togogenome.org/gene/10090:Apol7b ^@ http://purl.uniprot.org/uniprot/B1AQP7 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Or4a69 ^@ http://purl.uniprot.org/uniprot/Q8VF91 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Syndig1l ^@ http://purl.uniprot.org/uniprot/B2RRM8|||http://purl.uniprot.org/uniprot/Q3USQ7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||Expression is restricted to the caudate-putamen. Down-regulated in R6/2 transgenic mice, a model for Huntington disease.|||Membrane|||cis-Golgi network http://togogenome.org/gene/10090:Foxo1 ^@ http://purl.uniprot.org/uniprot/Q9R1E0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-259 and Lys-271 are necessary for autophagic cell death induction (By similarity). Deacetylated by SIRT2 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagic cell death (By similarity). Once in the nucleus, acetylated by CREBBP/EP300 (By similarity). Acetylation diminishes the interaction with target DNA and attenuates the transcriptional activity. It increases the phosphorylation at Ser-253, and is required for the transcriptional inhibition by FCOR (By similarity). Deacetylation by SIRT1 results in reactivation of the transcriptional activity (PubMed:15220471, PubMed:16076959, PubMed:17090532). Acetylation of FOXO1 diminishes its binding to PPARG in adipocytes. Deacetylated by SIRT2; deacetylation of FOXO1 directly increases its repressive binding to PPARG and inhibits adipocyte differentiation (PubMed:17681146, PubMed:19037106, PubMed:20519497, PubMed:21196578). Oxidative stress by hydrogen peroxide treatment appears to promote deacetylation and uncoupling of insulin-induced phosphorylation (By similarity). By contrast, resveratrol acts independently of acetylation (By similarity). Acetylated at Lys-420, promoting its localization to the nucleus and transcription factor activity (PubMed:25009184). Deacetylation at Lys-420 by SIRT6, promotes its translocation into the cytoplasm, preventing its transcription factor activity (PubMed:25009184, PubMed:27457971). Deacetylation and subsequent inhibition by SIRT6 has different effects depending on cell types: it inhibits gluconeogenesis in hepatocytes, promotes glucose sensing in pancreatic beta-cells and regulates lipid catabolism in brown adipocytes (PubMed:25009184, PubMed:27457971, PubMed:31442424).|||Cytoplasm|||Expressed in liver, white and brown adipose tissues (at protein level).|||Expression is regulated by KRIT1 (PubMed:20668652). Transiently up-regulated during adipogenesis (at protein level) (PubMed:18388859).|||In an animal model of diabetes mellitus type 2 (db/db mice), beta-cell islets exhibit increased levels of PPP2R1A leading to increased dephosphorylation at Thr-24 and Ser-253 and nuclear retention of FOXO1.|||In liver, barely expressed at 14.5 dpc, expression dramatically increases at 18.5 dpc. Abundantly expressed in neonate liver but levels strongly decrease in adult liver (at protein level).|||Interacts with EP300 and CREBBP; the interactions acetylate FOXO1. Interacts with the 14-3-3 proteins, YWHAG and YWHAZ; the interactions require insulin-stimulated phosphorylation on Thr-24, promote nuclear exit and loss of transcriptional activity. Interacts with SKP2; the interaction ubiquitinates FOXO1 leading to its proteasomal degradation. Interacts with PMRT1; methylates FOXO1, prevents PKB/AKT1 phosphorylation and retains FOXO1 in the nucleus (By similarity). Interacts (via an N-terminal domain) with FCOR; the interaction is direct, occurs in a forskolin-independent manner and prevents SIRT1 binding to FOXO1. Interacts (via the C-terminal half) with ATF4 (via its DNA-binding domain); the interaction occurs in osteoblasts, regulates glucose homeostasis via suppression of beta-cell proliferation and subsequent decrease in insulin production. Interacts with RUNX2; the interaction inhibits RUNX2 transcriptional activity and mediates the IGF1/insulin-dependent BGLAP expression in osteoblasts. Interacts with PPP2R1A; the interaction regulates the dephosphorylation of FOXO1 at Thr-24 and Ser-253 leading to its nuclear import. Binds to CDK1. Interacts with LRPPRC. Interacts with RUNX2; the interaction inhibits RUNX2 transcriptional activity and mediates the IGF1/insulin-dependent BGLAP expression in osteoblasts. Interacts with NLK. Interacts with SIRT1; the interaction results in the deacetylation of FOXO1 leading to activation of FOXO1-mediated transcription of genes involved in DNA repair and stress resistance. The interaction requires the presence of KRIT1 and is inhibited by FCOR. Interacts with SIRT2; the interaction is disrupted in response to oxidative stress or serum deprivation, leading to increased level of acetylated FOXO1, which promotes stress-induced autophagy by stimulating E1-like activating enzyme ATG7. Interacts (acetylated form) with ATG7; the interaction is increased in response to oxidative stress or serum deprivation and promotes the autophagic process leading to cell death. Interacts (acetylated form) with PPARG (PubMed:12754525, PubMed:15220471, PubMed:16917544, PubMed:17050673, PubMed:17681146, PubMed:19037106, PubMed:20061393, PubMed:20668652, PubMed:21471200, PubMed:22298775, PubMed:22417654, PubMed:22510882). Interacts with XBP1 isoform 2; this interaction is direct and leads to FOXO1 ubiquitination and degradation via the proteasome pathway (PubMed:21317886). Interacts (via the Fork-head domain) with CEBPA; the interaction increases when FOXO1 is deacetylated (PubMed:17090532, PubMed:17627282). Interacts with WDFY2 (PubMed:18388859). Forms a complex with WDFY2 and AKT1 (PubMed:18388859). Interacts with CRY1 (PubMed:28790135). Interacts with PPIA/CYPA; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (By similarity). Interacts with TOX4; FOXO1 is required for full induction of TOX4-dependent activity and the interaction is inhibited by insulin (PubMed:34914893).|||Methylation inhibits PKB/AKT1-mediated phosphorylation at Ser-253, promoting nuclear retention and increasing the transcriptional activity and cell death. Methylation increased by oxidative stress.|||Nucleus|||Null mice die around embryonic day 11 and exhibit abnormal angiogenesis. Defects are observed in branchial arches and there is remarkably impaired vascular development of embryos and yolk sacs. Exogeneous VEGF on FOX1-deficient endothelial cells show markedly different morphological response. Active osteocalcin/BGLAP as well as serum insulin and beta-cell and gonadal fat levels were increased, but there is no change in total fat content, lean mass, and body weight. Effect on RUNX2 activity was inhibited. FOXO1 and ATF4 double happlo-insufficient mice exhibit also an increase in insulin levels and beta cell proliferation, but there is an increase in insulin sensitivity demonstrated by an increase in expression of insulin-sensitizing hormone adiponectin. Gonadal fat levels and adipocyte numbers were decreased. Osteocalcin/BGLAP levels were unchanged.|||Phosphorylation by NLK promotes nuclear export and inhibits the transcriptional activity. In response to growth factors, phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1 promotes nuclear export and inactivation of transactivational activity. Phosphorylation on Thr-24 is required for binding 14-3-3 proteins. Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function. Stress signals, such as response to oxygen or nitric oxide, attenuate the PKB/AKT1-mediated phosphorylation leading to nuclear retention. Phosphorylation of Ser-326 is independent of IGF1 and leads to reduced function. Dephosphorylated on Thr-24 and Ser-253 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity). Phosphorylation of Ser-246 by CDK1 disrupts binding of 14-3-3 proteins leading to nuclear accumulation and has no effect on DNA-binding nor transcriptional activity. Phosphorylation by STK4/MST1 on Ser-209, upon oxidative stress, inhibits binding to 14-3-3 proteins and nuclear export (By similarity). PPIA/CYPA promotes its dephosphorylation on Ser-253 (By similarity).|||Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:12219087, PubMed:12754525, PubMed:15184386, PubMed:15220471, PubMed:16917544, PubMed:17090532, PubMed:17627282, PubMed:17681146, PubMed:20519497, PubMed:20668652, PubMed:21196578, PubMed:21335550, PubMed:21471200, PubMed:22298775, PubMed:22417654, PubMed:22510882, PubMed:27457971, PubMed:34914893). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:17090532, PubMed:21335550). Activity suppressed by insulin (PubMed:12754525, PubMed:17627282). Main regulator of redox balance and osteoblast numbers and controls bone mass (PubMed:21471200, PubMed:22298775). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (PubMed:21471200, PubMed:22298775). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (PubMed:32103177). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (PubMed:22298775). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (PubMed:21471200). Acts as an inhibitor of glucose sensing in pancreatic beta cells by acting as a transcription repressor and suppressing expression of PDX1 (PubMed:12219087, PubMed:27457971). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (PubMed:12754525, PubMed:25009184). Also promotes gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1 (By similarity). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (By similarity). Promotes neural cell death (By similarity). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (PubMed:21196578). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (By similarity). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity).|||Ubiquitinated, leading to proteasomal degradation (PubMed:28790135). Ubiquitinated by SKP2 (By similarity). http://togogenome.org/gene/10090:Psca ^@ http://purl.uniprot.org/uniprot/P57096 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with CHRNA4.|||May act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits nicotine-induced signaling probably implicating alpha-3:beta-2- or alpha-7-containing nAChRs.|||May be involved in the regulation of cell proliferation.|||Predominantly expressed in prostate. Also found in spleen, liver, lung, prostate, kidney and testis. Expressed in brain cortex; expression is increased in transgenic mouse model of Alzheimer disease (at protein level). http://togogenome.org/gene/10090:Mtnr1a ^@ http://purl.uniprot.org/uniprot/Q14AC3|||http://purl.uniprot.org/uniprot/Q61184 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity (By similarity).|||High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.|||Membrane http://togogenome.org/gene/10090:Ip6k2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXT7|||http://purl.uniprot.org/uniprot/Q80V72 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the inositol phosphokinase (IPK) family.|||Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5) (By similarity). May play a role in the regulation of Na(+)-dependent phosphate cotransport, possibly via its role in diphosphoinositol pentakisphosphate (InsP7/PP-InsP5) biosynthesis (By similarity).|||Highly expressed in brain and lung, and at slightly lower levels in liver, kidney and testis.|||Nucleus http://togogenome.org/gene/10090:Gm4787 ^@ http://purl.uniprot.org/uniprot/B2RUD9 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Or8b54 ^@ http://purl.uniprot.org/uniprot/Q7TRC0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tgm7 ^@ http://purl.uniprot.org/uniprot/A2ART8 ^@ Cofactor|||Similarity ^@ Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 1 Ca(2+) ion per subunit. http://togogenome.org/gene/10090:Sobp ^@ http://purl.uniprot.org/uniprot/Q0P5V2 ^@ Developmental Stage|||Function|||Similarity|||Subunit ^@ Belongs to the SOBP family.|||Implicated in development of the cochlea.|||Interacts (via SIM domains) with SUMO1 and SUMO2.|||Present at 14.5 dpc throughout the developing brain, with high expression in the cortical plate. During postnatal development, detected in all neurons, with an intense expression in the limbic system, with highest levels throughout layer V neurons in the cortex, the hippocampus, the pyriform cortex, the dorsomedial nucleus of the thalamus, the amygdala, and the hypothalamus. Cortical expression is strong throughout development, with no clear dorsoventral or rostrocaudal gradient, highest levels at P10 in layers II/III and V and in the subplate. Relatively strong expression in the mitral cells layer and anterior olfactory bulb, as well as in the Purkinje cell layer in the cerebellum. Expression in the limbic system postnatally corresponds to the time window of active synaptogenesis. http://togogenome.org/gene/10090:Stip1 ^@ http://purl.uniprot.org/uniprot/Q60864 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a co-chaperone for HSP90AA1. Mediates the association of the molecular chaperones HSPA8/HSC70 and HSP90.|||Cytoplasm|||Dynein axonemal particle|||In vitro kinase assay failed to detect phosphorylation by MAPKAPK2.|||Nucleus|||Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2 (By similarity). Forms a complex with HSPA8/HSC70, HSPCA/HSP-86 and HSPCB/HSP-84 (PubMed:8999875). Interacts with PACRG. Interacts with EEF1AKMT3 (By similarity). Interacts with HSP90/HSP90AA1; the interaction dissociates the PPP5C:HSP90AA1 interaction. Interacts with FLCN, FNIP1 and FNIP2. Interacts with HSPA8/HSC70 (By similarity). Interacts with HSP90AB1; upon SMYD2-dependent HSP90AB1 methylation (By similarity).|||The TPR 1 repeat interacts with the C-terminal of HSC70. The TPR 4, 5 and 6 repeats (also called TPR2A domain) and TPR 7, 8 and 9 repeats (also called TPR2B domain) interact with HSP90 (By similarity). http://togogenome.org/gene/10090:Or13a21 ^@ http://purl.uniprot.org/uniprot/Q8VGT4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or11m3 ^@ http://purl.uniprot.org/uniprot/Q8VFD8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nrbf2 ^@ http://purl.uniprot.org/uniprot/Q8VCQ3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||During embryonic brain development detected in the cerebral cortex at 14 dpc; expressed in the walls of the third and fourth ventricles, and in the hippocampus. In the adult brain, predominantly expressed in Purkinje cells of the cerebellum and neurons in the CA3 region of the hippocampus (PubMed:18619852).|||Interacts with RRARA, PPARD and PPARG. Interacts with THRB, RARA, RARG and RXRA in the presence of bound ligand (By similarity). Interacts with SCOC (By similarity). Associates with the PI3K complex I (PI3KC3-C1); the direct binding partner in the complex is reported variably as PIK3R4 or ATG14 (PubMed:24849286).|||Involved in starvation-induced autophagy probably by its association with PI3K complex I (PI3KC3-C1). However, effects has been described variably. Involved in the induction of starvation-induced autophagy (By similarity). Stabilzes PI3KC3-C1 assembly and enhances ATG14-linked lipid kinase activity of PIK3C3 (PubMed:24849286). Proposed to negatively regulate basal and starvation-induced autophagy and to inhibit PIK3C3 activity by modulating interactions in PI3KC3-C1 (By similarity). May be involved in autophagosome biogenesis (By similarity). May play a role in neural progenitor cell survival during differentiation (PubMed:18619852).|||Involved in the induction of starvation-induced autophagy. Modulates ATG14-linked lipid kinase activity of PIK3C3 and stabilzes PI3K complex I (PI3KC3-C1) assembly (PubMed:24849286). May play a role in neural progenitor cell survival during differentiation (PubMed:18619852).|||May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro) (By similarity).|||Nucleus|||autophagosome http://togogenome.org/gene/10090:Phf20l1 ^@ http://purl.uniprot.org/uniprot/A0A5S8DHC4|||http://purl.uniprot.org/uniprot/Q8CCJ9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with methylated DNMT1 (DNMT1K142me1). Interacts with SOX2.|||Is a negative regulator of proteasomal degradation of a set of methylated proteins, including DNMT1 and SOX2 (By similarity). Involved in the maintainance of embryonic stem cells pluripotency, through the regulation of SOX2 levels (PubMed:29358331).|||Nucleus http://togogenome.org/gene/10090:Spaca5 ^@ http://purl.uniprot.org/uniprot/A0A077S1H9|||http://purl.uniprot.org/uniprot/A2AE20 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 22 family.|||Secreted http://togogenome.org/gene/10090:Pak1ip1 ^@ http://purl.uniprot.org/uniprot/Q9DCE5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with PAK1.|||Negatively regulates the PAK1 kinase. PAK1 is a member of the PAK kinase family, which has been shown to play a positive role in the regulation of signaling pathways involving MAPK8 and RELA. PAK1 exists as an inactive homodimer, which is activated by binding of small GTPases such as CDC42 to an N-terminal regulatory domain. PAK1IP1 also binds to the N-terminus of PAK1, and inhibits the specific activation of PAK1 by CDC42. May be involved in ribosomal large subunit assembly.|||nucleolus http://togogenome.org/gene/10090:Mt4 ^@ http://purl.uniprot.org/uniprot/P47945|||http://purl.uniprot.org/uniprot/Q3V2E2 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the metallothionein superfamily. Type 1 family.|||Expressed exclusively in stratified squamous epithelia associated with oral epithelia, esophagus, upper stomach, tail, footpads and neonatal skin.|||Metallothioneins have a high content of cysteine residues that bind various heavy metals.|||Seems to bind zinc and copper. Could play a special role in regulating zinc metabolism during the differentiation of stratified epithelia. http://togogenome.org/gene/10090:Ptrh2 ^@ http://purl.uniprot.org/uniprot/Q8R2Y8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PTH2 family.|||Mitochondrion outer membrane|||Monomer.|||The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis.|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Vmn2r53 ^@ http://purl.uniprot.org/uniprot/L7N473 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Opn3 ^@ http://purl.uniprot.org/uniprot/Q9WUK7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Cell membrane|||Cytoplasm|||Expressed at substantial levels in the dorsal pons at 18.5 dpc (PubMed:10234000). Expressed in Purkinje cells at P4, with expression becoming striped at P20 (PubMed:10234000). Expressed in the cerebral cortex from 18.5 dpc with a rostrocaudal gradient of expression becoming evident at P20 (PubMed:10234000).|||Expressed in the eye (at protein level) (PubMed:30284927). Expressed in tracheal airway smooth muscle (PubMed:30284927). Expressed in brown adipocyte tissue; expression becomes more abundant during differentiation (PubMed:32040503). Strongly expressed in brain (PubMed:10234000). Highly expressed in the preoptic area and paraventricular nucleus of the hypothalamus (PubMed:10234000). Shows highly patterned expression in other regions of the brain, being enriched in selected regions of the cerebral cortex, cerebellar Purkinje cells, a subset of striatal neurons, selected thalamic nuclei, and a subset of interneurons in the ventral horn of the spinal cord (PubMed:10234000).|||G-protein coupled receptor which selectively activates G proteins via ultraviolet A (UVA) light-mediated activation in the skin (PubMed:30284927). Binds both 11-cis retinal and all-trans retinal (By similarity). Regulates melanogenesis in melanocytes via inhibition of alpha-MSH-induced MC1R-mediated cAMP signaling, modulation of calcium flux, regulation of CAMK2 phosphorylation, and subsequently phosphorylation of CREB, p38, ERK and MITF in response to blue light (By similarity). Plays a role in melanocyte survival through regulation of intracellular calcium levels and subsequent BCL2/RAF1 signaling (By similarity). Additionally regulates apoptosis via cytochrome c release and subsequent activation of the caspase cascade (By similarity). Required for TYR and DCT blue light-induced complex formation in melanocytes (By similarity). Involved in keratinocyte differentiation in response to blue-light (By similarity). Required for the UVA-mediated induction of calcium and mitogen-activated protein kinase signaling resulting in the expression of MMP1, MMP2, MMP3, MMP9 and TIMP1 in dermal fibroblasts (By similarity). Plays a role in light-mediated glucose uptake, mitochondrial respiration and fatty acid metabolism in brown adipocyte tissues (PubMed:32040503). May be involved in photorelaxation of airway smooth muscle cells, via blue-light dependent GPCR signaling pathways (PubMed:30284927).|||Interacts with MC1R; the interaction results in a decrease in MC1R-mediated cAMP signaling and ultimately a decrease in melanin production in melanocytes.|||No visible phenotype (PubMed:32040503). Increased weight gain on a high fat diet, as a result of increased fat mass and increased insulin resistance (PubMed:32040503). Increased basal glucose uptake in brown adipocytes, potentially as a result of decreased GLUT1 expression (PubMed:32040503). Significantly reduced lipocytic rate, mitochondrial DNA expression and cytochrome C oxidase activity in brown adipocyte tissues (PubMed:32040503). Loss of light-mediated increase in glucose uptake, mitochondrial respiration, thermogenic capacity and lipid metabolism-related gene expression in brown adipocyte tissues (PubMed:32040503). Impaired maximum thermogenic capacity with reduced heat production and reduced oxygen consumption in response to norepinephrine treatment in brown adipocytes (PubMed:32040503). http://togogenome.org/gene/10090:Actg2 ^@ http://purl.uniprot.org/uniprot/P63268|||http://purl.uniprot.org/uniprot/Q3UJ36 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.|||Belongs to the actin family.|||Expressed in tissues containing smooth muscle particularly the intestines and bladder.|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Methylated at His-74 by SETD3.|||Monomethylation at Lys-85 (K85me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.|||N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.|||Oxidation of Met-45 and Met-48 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.|||cytoskeleton http://togogenome.org/gene/10090:Stoml3 ^@ http://purl.uniprot.org/uniprot/B2RS16|||http://purl.uniprot.org/uniprot/Q6PE84 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the band 7/mec-2 family.|||Cell membrane|||Expressed by all dorsal root ganglion neurons and is selectively expressed in neuronal tissues. Detected in olfactory epithelium.|||Homodimer. Interacts with PIEZO1 and PIEZO2.|||In deficient mice 35% of skin mechanoreceptors do not respond to mechanical stimuli. In addition, mechanosensitive ion channels find in many sensory neurons do not function. Tactile-driven behaviors are also impaired in mutant mice, including touch-evoked pain caused by neuropathic injury.|||Required for the function of many mechanoreceptors. Modulate mechanotransduction channels and acid-sensing ion channels (ASIC) proteins. Potentiates PIEZO1 and PIEZO2 function by increasing their sensitivity to mechanical stimulations. http://togogenome.org/gene/10090:Ubxn11 ^@ http://purl.uniprot.org/uniprot/Q9D572 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with GNA12, GNA13, RND1, RND2 and RND3.|||May be involved in the reorganization of actin cytoskeleton mediated by RND1, RND2 and RND3. Promotes RHOA activation mediated by GNA12 and GNA13 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Nbr1 ^@ http://purl.uniprot.org/uniprot/A1L329|||http://purl.uniprot.org/uniprot/A2A4N5|||http://purl.uniprot.org/uniprot/A2A4N8|||http://purl.uniprot.org/uniprot/P97432|||http://purl.uniprot.org/uniprot/Q05BC8|||http://purl.uniprot.org/uniprot/Q6ZQK3 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain.|||Homooligomer and heterooligomer. Interacts with TRIM55 (By similarity). Interacts with titin/TTN (By similarity). Interacts with RNF29, USP8, MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1 and GABARAPL2. Binds to ubiquitin and ubiquitinated proteins. Interacts with SQSTM1. Interacts with TAX1BP1. Interacts with IRF3; this interaction mediates autophagic degradation of IRF3 (By similarity). Interacts with IL12A and IL12B (PubMed:34374750).|||In response to oxidative stress.|||Lysosome|||M line|||NBR1-conditional knockout mice are not affected concerning general autophagy. However, the deletion results in a slight but significant reduction on the number and size of SQSTM1 liquid droplets.|||Phosphorylated by GSK3A; this phosphorylation inhibits NBR1 involvement in the formation of ubiquitinated protein aggregates.|||The PB1 domain mediates interaction with SQSTM1.|||Ubiquitin-binding autophagy adapter that participates in different processes including host defense or intracellular homeostasis (PubMed:31916398, PubMed:34374750). Possesses a double function during the selective autophagy by acting as a shuttle bringing ubiquitinated proteins to autophagosomes and also by participating in the formation of protein aggregates. Plays a role in the regulation of the innate immune response by modulating type I interferon production and targeting ubiquitinated IRF3 for autophagic degradation (By similarity). In response to oxidative stress, promotes an increase in SQSTM1 levels, phosphorylation, and body formation by preventing its autophagic degradation (PubMed:31916398). In turn, activates the KEAP1-NRF2/NFE2L2 antioxidant pathway (PubMed:31916398). Plays also non-autophagy role by mediating the shuttle of IL-12 to late endosome for subsequent secretion (PubMed:34374750).|||autophagosome http://togogenome.org/gene/10090:Ift22 ^@ http://purl.uniprot.org/uniprot/Q9DAI2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88. Interacts with IFT88.|||Small GTPase-like component of the intraflagellar transport (IFT) complex B.|||cilium http://togogenome.org/gene/10090:Or2b6 ^@ http://purl.uniprot.org/uniprot/Q60890 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Trim12a ^@ http://purl.uniprot.org/uniprot/Q99PQ1 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||Expressed in embryonic CNS, liver, kidney, olfactory epithelium. http://togogenome.org/gene/10090:Ppp4r1 ^@ http://purl.uniprot.org/uniprot/Q8K2V1 ^@ Function|||Subunit ^@ Regulatory subunit of serine/threonine-protein phosphatase 4. May play a role in regulation of cell division in renal glomeruli. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3 (By similarity).|||Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complex PPP4C-PPP4R1. Interacts with HDAC3 (By similarity). http://togogenome.org/gene/10090:H2bc11 ^@ http://purl.uniprot.org/uniprot/P10853 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Hsf5 ^@ http://purl.uniprot.org/uniprot/Q5ND04 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HSF family.|||Expressed in adult but not fetal testis. Not expressed in ovary.|||May act as a transcriptional factor.|||Nucleus http://togogenome.org/gene/10090:Pus10 ^@ http://purl.uniprot.org/uniprot/Q9D3U0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pseudouridine synthase Pus10 family.|||Cytoplasm|||Interacts with components of the microprocessor complex DROSHA and DGCR8.|||Mitochondrion|||Nucleus|||Protein with different functions depending on its subcellular location: involved in miRNA processing in the nucleus and acts as a tRNA pseudouridylate synthase in the cytoplasm. In the cytoplasm, acts as a pseudouridylate synthase by catalyzing synthesis of pseudouridine(54) and pseudouridine(55) from uracil-54 and uracil-55, respectively, in the psi GC loop of a subset of tRNAs. tRNA pseudouridylate synthase activity is enhanced by the presence of 1-methyladenosine at position 53-61 of tRNAs. Does not show tRNA pseudouridylate synthase activity in the nucleus. In the nucleus, promotes primary microRNAs (pri-miRNAs) processing independently of its RNA pseudouridylate synthase activity. Binds pri-miRNAs. Modulator of TRAIL/TNFSF10-induced cell death via activation of procaspase-8 and BID cleavage. Required for the progression of the apoptotic signal through intrinsic mitochondrial cell death.|||Proteolytically cleaved during TRAIL-induced cell death. Cleaved, in vitro, either by caspase-3 (CASP3) or caspase-8 (CASP8). http://togogenome.org/gene/10090:Junb ^@ http://purl.uniprot.org/uniprot/P09450|||http://purl.uniprot.org/uniprot/Q569U6 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. Jun subfamily.|||Binds DNA as a homodimer or as a heterodimer with another member of the Jun/Fos family (By similarity). Component of an AP-1 transcription factor complex composed of JUN-FOS heterodimers (PubMed:2498083). As part of the AP-1 transcription factor complex, forms heterodimers with FOSB, thereby binding to the AP-1 consensus sequence and stimulating transcription (PubMed:2498083). Interacts with NFE2 (via its WW domains) (By similarity).|||By growth factors.|||Nucleus|||Transcription factor involved in regulating gene activity following the primary growth factor response. Binds to the DNA sequence 5'-TGA[GC]TCA-3'. Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to an AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity (PubMed:2498083).|||Ubiquitinated by ITCH, leading to its degradation. http://togogenome.org/gene/10090:Lsm7 ^@ http://purl.uniprot.org/uniprot/Q9CQQ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome. Interacts with TACC1.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA. http://togogenome.org/gene/10090:Slc12a7 ^@ http://purl.uniprot.org/uniprot/B9EIV8|||http://purl.uniprot.org/uniprot/Q9WVL3 ^@ Activity Regulation|||Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by N-ethylmaleimide (NEM). Inhibited by furosemide, DIDS and bumetanide. The inhibition is much stronger in the presence of 50 mM K(+) in the uptake medium. Inhibited by DIOA. Inhibited by WNK3.|||Belongs to the SLC12A transporter family.|||Cell membrane|||Defects in Slc12a7 are a cause of deafness due to the progressive degeneration of outer and inner hair cells in the cochlea and of neurons in the cochlear ganglion, leading to the loss of the organ of Corti.|||Detected in proximal tubules in the kidney, in particular in basolateral membranes of intercalated cells in the cortical collecting duct.|||Glycosylation at Asn-331 and Asn-344 is required for proper trafficking to the cell surface, and augments protein stability.|||Homomultimer and heteromultimer with other K-Cl cotransporters.|||In 8 day old mice, before the onset of hearing, detected in membranes of the stria vascularis and in most cells of the organ of Corti. At P14, when the organ of Corti has matured, expression is no longer detected in hair cells and the stria, but is restricted to Deiters' cells that are supporting outer hair cells and to phalangeal cells enveloping the inner hair cells.|||Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:11551954, PubMed:12106695). May mediate K(+) uptake into Deiters' cells in the cochlea and contribute to K(+) recycling in the inner ear. Important for the survival of cochlear outer and inner hair cells and the maintenance of the organ of Corti (PubMed:11976689). May be required for basolateral Cl(-) extrusion in the kidney and contribute to renal acidification (Probable).|||Membrane http://togogenome.org/gene/10090:Hagh ^@ http://purl.uniprot.org/uniprot/A0A0R4J052|||http://purl.uniprot.org/uniprot/G5E8T9|||http://purl.uniprot.org/uniprot/Q99KB8 ^@ Caution|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||Binds 2 Zn(2+) ions per subunit.|||Cytoplasm|||Mitochondrion matrix|||Monomer.|||Only one single gene encoding glyoxalase II has been identified in vertebrates. In yeast and higher plants, separate genes encode the cytosolic and mitochondrial forms of glyoxalase II.|||Produced by alternative splicing. Also produced by alternative initiation at Met-50 of isoform 1. Alternative initiation has been proven in human.|||Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid. http://togogenome.org/gene/10090:Mto1 ^@ http://purl.uniprot.org/uniprot/G5E889|||http://purl.uniprot.org/uniprot/Q923Z3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MnmG family.|||Involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.|||Mitochondrion|||Ubiquitously expressed in various tissues, but with markedly elevated expression in tissues of high metabolic rates. http://togogenome.org/gene/10090:Gatb ^@ http://purl.uniprot.org/uniprot/Q99JT1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).|||Belongs to the GatB/GatE family. GatB subfamily.|||Mitochondrion|||Subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (GATB) and C (GATC) subunits. http://togogenome.org/gene/10090:Atp6v1e1 ^@ http://purl.uniprot.org/uniprot/P50518 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the V-ATPase E subunit family.|||Expressed within the midpiece of sperm tail (at protein level) (PubMed:11872743, PubMed:23055941). Kidney; localizes to early distal nephron, encompassing thick ascending limbs and distal convoluted tubules (at protein level) (PubMed:29993276).|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941). Interacts with ALDOC (By similarity). Interacts with RAB11B (By similarity).|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Sdccag8 ^@ http://purl.uniprot.org/uniprot/Q80UF4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell junction|||Expressed in liver, kidney, spleen, brain, heart and muscle. Expressed in photoreceptor cells of the retina.|||Homodimer (PubMed:12559564). Interacts with OFD1; the interaction is direct (By similarity). Interacts with FAM161A (By similarity). Interacts with RABEP2, ERC1 and CEP131 (By similarity).|||In renal epithelial cells gene knockdown results in the formation of spheroids with architectural defects characterized by disturbed localization of beta-catenin (CTNNB1) at the basolateral membrane, fewer tight junctions and an irregular lumen (PubMed:20835237). SDCCAG8-deficient mice display developmental bone malformations with rib cage abnormalities.|||Plays a role in the establishment of cell polarity and epithelial lumen formation (PubMed:20835237). Also plays an essential role in ciliogenesis and subsequent Hedgehog signaling pathway that requires the presence of intact primary cilia for pathway activation. Mechanistically, interacts with and mediates RABEP2 centrosomal localization which is critical for ciliogenesis (PubMed:27224062).|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Med10 ^@ http://purl.uniprot.org/uniprot/Q9CXU0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 10 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ophn1 ^@ http://purl.uniprot.org/uniprot/Q99J31 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with HOMER1. Interacts with AMPA receptor complexes. Interacts with SH3GL2 (endophilin-A1) (By similarity). Interacts (via C-terminus) with NR1D1.|||Postsynapse|||Presynapse|||Stimulates GTP hydrolysis of members of the Rho family. Its action on RHOA activity and signaling is implicated in growth and stabilization of dendritic spines, and therefore in synaptic function. Critical for the stabilization of AMPA receptors at postsynaptic sites. Critical for the regulation of synaptic vesicle endocytosis at presynaptic terminals (By similarity). Required for the localization of NR1D1 to dendrites, can suppress its repressor activity and protect it from proteasomal degradation.|||axon|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Psapl1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1A5|||http://purl.uniprot.org/uniprot/Q8C1C1 ^@ Function|||Subcellular Location Annotation ^@ May activate the lysosomal degradation of sphingolipids.|||Secreted http://togogenome.org/gene/10090:Fancg ^@ http://purl.uniprot.org/uniprot/Q9EQR6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. In complex with FANCF, FANCA and FANCL, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins. The complex with FANCC and FANCG may also include EIF2AK2 and HSP70.|||DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Candidate tumor suppressor gene (By similarity).|||Highest expression levels in spleen, thymus and testis.|||Nucleus http://togogenome.org/gene/10090:Or5ar1 ^@ http://purl.uniprot.org/uniprot/Q149M3|||http://purl.uniprot.org/uniprot/Q8VGS3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Copper binding enhances receptor activity in response to odorant binding.|||Membrane|||Olfactory receptor that is activated by the binding of organosulfur odorants with thioether groups such as (methylthio)methanethiol (MTMT). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (Probable). http://togogenome.org/gene/10090:Vax2 ^@ http://purl.uniprot.org/uniprot/Q14B19|||http://purl.uniprot.org/uniprot/Q9WTP9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 9.5 dpc, expressed solely in the ventral halves of the optic stalks and vesicles without proximo-distal restriction. Expression in the optic stalk diminishes after 11.5 dpc and becomes restricted to the inner layer of optic cup in its ventral half. Expression persists in the ventral halves of all neural retina layers (inner and outer nuclear layer) at 14.5 dpc and 16.5 dpc, and the ganglion cell layer, inner nuclear layer and photoreceptor layer in the adult.|||Belongs to the EMX homeobox family.|||Expressed in the developing and mature retina.|||Nucleus|||Transcription factor that may function in dorsoventral specification of the forebrain. Regulates the expression of Wnt signaling antagonists including the expression of a truncated TCF7L2 isoform that cannot bind CTNNB1 and acts therefore as a potent dominant-negative Wnt antagonist. Plays a crucial role in eye development and, in particular, in the specification of the ventral optic vesicle. May be a regulator of axial polarization in the retina. http://togogenome.org/gene/10090:Dab2ip ^@ http://purl.uniprot.org/uniprot/Q3UHC7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Down-regulated in prostate cancer and medulloblastoma.|||Exists in a closed inactive form by an intramolecular interaction between the N- and the C-terminal domains. The proline-rich motif is critical both for PI3K-AKT activity inhibition and MAP3K5 activation. The PH and C2 domains are necessary for the binding to phosphatidylinositol phosphate. The Ras-GAP domain is necessary for its tumor-suppressive function (By similarity). The C2 and GAP domains constitutively bind to MAP3K5 and facilitate the release of 14-3-3 proteins from MAP3K5. The PH and Ras-GAP domains, but not the NPXY motif, are crucial for its cell membrane localization and neuronal migration function. The PH domain is necessary but not sufficient to activate the JNK signaling pathway through ERN1.|||Expressed in cortical plate neurons at 16 dpc. Expressed in the neocortex, including the cortical plate (CP) at 16.5 dpc, onward (at protein level). Expressed in brain at 13.5 dpc, onward. Expressed during embryogenesis in the vasculature.|||Expressed in vascular endothelium of muscle and aorta, in smooth muscle cells of aorta and epithelial cells of lung. Expressed throughout the brain, including olfactory bulb, hypothalamus, cerebellum and cerebral cortex. Expressed in the soma and processes of neurons in a variety of brain structures, including the developing cerebral cortex, CA1 pyramidal neurons and Purkinje cells. Poorly expressed in medulloblastoma cells compared to cerebellar precursor proliferating progenitor cells (at protein level). Highly expressed in the brain, salivary gland, and testis; moderate expression in kidney and heart. Low expression in the lung, seminal vesicle, ventral prostate, epididymis, liver, and bladder. Very low expression in the coagulation gland and skeleton muscles. Lowest expression seen in spleen.|||Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Involved in several processes such as innate immune response, inflammation and cell growth inhibition, apoptosis, cell survival, angiogenesis, cell migration and maturation. Also plays a role in cell cycle checkpoint control; reduces G1 phase cyclin levels resulting in G0/G1 cell cycle arrest. Mediates signal transduction by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF), interferon (IFN) or lipopolysaccharide (LPS). Modulates the balance between phosphatidylinositol 3-kinase (PI3K)-AKT-mediated cell survival and apoptosis stimulated kinase (MAP3K5)-JNK signaling pathways; sequesters both AKT1 and MAP3K5 and counterbalances the activity of each kinase by modulating their phosphorylation status in response to pro-inflammatory stimuli. Acts as a regulator of the endoplasmic reticulum (ER) unfolded protein response (UPR) pathway; specifically involved in transduction of the ER stress-response to the JNK cascade through ERN1. Mediates TNF-alpha-induced apoptosis activation by facilitating dissociation of inhibitor 14-3-3 from MAP3K5; recruits the PP2A phosphatase complex which dephosphorylates MAP3K5 on 'Ser-966', leading to the dissociation of 13-3-3 proteins and activation of the MAP3K5-JNK signaling pathway in endothelial cells. Mediates also TNF/TRAF2-induced MAP3K5-JNK activation, while it inhibits CHUK-NF-kappa-B signaling. Acts a negative regulator in the IFN-gamma-mediated JAK-STAT signaling cascade by inhibiting smooth muscle cell (VSMCs) proliferation and intimal expansion, and thus, prevents graft arteriosclerosis (GA). Acts as a GTPase-activating protein (GAP) for the ADP ribosylation factor 6 (ARF6) and Ras. Promotes hydrolysis of the ARF6-bound GTP and thus, negatively regulates phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent TLR4-TIRAP-MyD88 and NF-kappa-B signaling pathways in endothelial cells in response to lipopolysaccharides (LPS). Binds specifically to phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 3-phosphate (PtdIns3P). In response to vascular endothelial growth factor (VEGFA), acts as a negative regulator of the VEGFR2-PI3K-mediated angiogenic signaling pathway by inhibiting endothelial cell migration and tube formation. In the developing brain, promotes both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex in a glial-dependent locomotion process. Probable downstream effector of the Reelin signaling pathway; promotes Purkinje cell (PC) dendrites development and formation of cerebellar synapses. Functions also as a tumor suppressor protein in prostate cancer progression; prevents cell proliferation and epithelial-to-mesenchymal transition (EMT) through activation of the glycogen synthase kinase-3 beta (GSK3B)-induced beta-catenin and inhibition of PI3K-AKT and Ras-MAPK survival downstream signaling cascades, respectively.|||In response to TNF-alpha-induction, phosphorylated at Ser-728; phosphorylation leads to a conformational change, and thus, increases its association with 14-3-3 proteins, MAP3K5, RIPK1 and TRAF2 in endothelial cells; also stimulates regulatory p85 subunit sequestring and PI3K-p85 complex activity inhibition.|||Mice are viable and fertile but show a number of cerebellar abnormalities such as a delay in the Purkinje cell (PC) dendrites development and a disruption of late-born cortical neurons migration. Develope a prostate hyperplasia in epithelial compartment at 6 months of age. Show normal vasculature development but enhanced inflammatory angiogenesis.|||On plasma membrane, exists in an inactive form complexed with TNFR1; in response to TNF-alpha, dissociates from TNFR1 complex, translocates to cytoplasm and forms part of an intracellular signaling complex comprising TRADD, RIPK1, TRAF2 and MAP3K5. Interacts with DAB1. Part of a cytoplasmic complex made of HIPK1, DAB2IP and MAP3K5 in response to TNF-alpha; this complex formation promotes MAP3K5-JNK activation and subsequent apoptosis. Interacts (via N-terminal domain) with JAK2; the interaction occurs in a IFNG/IFN-gamma-dependent manner and inhibits JAK2 autophosphorylation activity. Interacts (via C2 domain) with GSK3B; the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts (via proline-rich motif) with a regulatory p85 subunit (via SH3 domain) of the PI3K complex; the interaction inhibits the PI3K-AKT complex activity in a TNF-alpha-dependent manner in prostate cancer (PCa) cells. Interacts with AKT1; the interaction is increased in a TNF-alpha-induced manner. Interacts (via C2 domain and active form preferentially) with KDR/VEGFR2 (tyrosine-phosphorylated active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts (via N-terminus C2 domain) with MAP3K5 ('Ser-966' dephosphorylated form preferentially); the interaction occurs in a TNF-alpha-induced manner. Interacts (via Ras-GAP domain) with the catalytic subunit of protein phosphatase PP2A; the interaction occurs in resting endothelial cells, is further enhanced by TNF-alpha stimulation and is required to bridge PP2A to MAP3K5. Interacts (via C-terminus PER domain) with TRAF2 (via zinc fingers); the interaction occurs in a TNF-alpha-dependent manner. Interacts with 14-3-3 proteins; the interaction occurs in a TNF-alpha-dependent manner. Interacts (via Ras-GAP domain) with RIPK1 (via kinase domain); the interaction occurs in a TNF-alpha-dependent manner (By similarity). Interacts (via PH domain) with ERN1. Interacts with TRAF2. Interacts (via NPXY motif) with DAB2 (via PID domain).|||dendrite http://togogenome.org/gene/10090:Dnajc22 ^@ http://purl.uniprot.org/uniprot/Q8CHS2 ^@ Function|||Subcellular Location Annotation ^@ May function as a co-chaperone.|||Membrane http://togogenome.org/gene/10090:Gpat3 ^@ http://purl.uniprot.org/uniprot/Q8C0N2 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) by incorporating an acyl moiety at the sn-1 position of the glycerol backbone (PubMed:17170135). Also converts LPA into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Protects cells against lipotoxicity (By similarity).|||During adipocyte differentiation.|||Endoplasmic reticulum membrane|||Most abundant in epididymal fat, followed by small intestine, brown adipose tissue, kidney, heart and colon.|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate. http://togogenome.org/gene/10090:Tspan10 ^@ http://purl.uniprot.org/uniprot/Q3UFS7|||http://purl.uniprot.org/uniprot/Q3UGA5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Spata48 ^@ http://purl.uniprot.org/uniprot/Q5NC83 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Tissue Specificity ^@ Essential for normal spermatogenesis.|||Mice have smaller testis and show impaired spermatogenesis.|||Testis specific. Expressed at the spermatid stage.|||Undetectable until 20 days post partum (dpp), and becomes detectable only after 22-30 dpp (PubMed:22110678). Expressed after postnatal day 15 and expression gradually increases with age (PubMed:29700843). http://togogenome.org/gene/10090:Gnpat ^@ http://purl.uniprot.org/uniprot/P98192|||http://purl.uniprot.org/uniprot/Q545P6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GPAT/DAPAT family.|||Dihydroxyacetonephosphate acyltransferase involved in plasmalogen biosynthesis.|||Highly expressed in liver and testis. Lower levels in heart, brain, lung and kidney. Detected in spleen.|||May be part of a heterotrimeric complex composed of DAP-AT, ADAP-S and a modified form of DAP-AT.|||Peroxisome membrane|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate. http://togogenome.org/gene/10090:Ubqln4 ^@ http://purl.uniprot.org/uniprot/Q99NB8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Cytoplasm|||Detected in testis, ovary, thyroid, kidney, thymus, heart, liver, lung and spleen (at protein level). Highly expressed in heart, skeletal muscle, kidney, liver and brain. Detected at lower levels in testis, lung and spleen.|||Endoplasmic reticulum|||Homooligomer (By similarity). Binds signal sequences of proteins that are targeted to the endoplasmic reticulum (PubMed:11162551). Interacts (via UBA domain) with GJA1 (not ubiquitinated) and with ubiquitin; both compete for the same binding site (PubMed:18079109, PubMed:20127391, PubMed:20940304). Interacts (via UBA domain) with ubiquitin and with polyubiquitin chains (PubMed:20940304). Interacts (via ubiquitin-like domain) with PSMD2 and PSMD4, regulatory subunits of the 26S proteasome (PubMed:18079109). Interacts with ATXN1/SCA1; interaction with ATXN1 inhibits polyubiquitination of UBQLN4 and interferes with PSMD4 binding (By similarity). Interacts with HERPUD1 (By similarity). Interacts (via ubiquitin-like domain) with UBQLN1 (via UBA domain) (By similarity). Interacts with UBQLN2 (By similarity). Interacts (via STI1 1 and 2 domains) with MAP1LC3A/B/C (By similarity). Interacts with BAG6 (By similarity). Interacts with MRE11 (when ubiquitinated); interaction with ubiquitinated MRE11 leads to MRE11 removal from chromatin (By similarity). Interacts with DESI1/POST; leading to nuclear export (By similarity). Interacts with BCL2A1 and BCL2L10 (By similarity).|||Nucleus|||Phosphorylated by ATM at Ser-313 in response to DNA damage, leading to localization in the nucleus and recruitment to sites of DNA damage.|||Regulator of protein degradation that mediates the proteasomal targeting of misfolded, mislocalized or accumulated proteins (By similarity). Acts by binding polyubiquitin chains of target proteins via its UBA domain and by interacting with subunits of the proteasome via its ubiquitin-like domain (By similarity). Key regulator of DNA repair that represses homologous recombination repair: in response to DNA damage, recruited to sites of DNA damage following phosphorylation by ATM and acts by binding and removing ubiquitinated MRE11 from damaged chromatin, leading to MRE11 degradation by the proteasome (By similarity). MRE11 degradation prevents homologous recombination repair, redirecting double-strand break repair toward non-homologous end joining (NHEJ) (By similarity). Specifically recognizes and binds mislocalized transmembrane-containing proteins and targets them to proteasomal degradation (By similarity). Collaborates with DESI1/POST in the export of ubiquitinated proteins from the nucleus to the cytoplasm (By similarity). Plays a role in the regulation of the proteasomal degradation of non-ubiquitinated GJA1 (PubMed:18079109, PubMed:20940304). Acts as an adapter protein that recruits UBQLN1 to the autophagy machinery (By similarity). Mediates the association of UBQLN1 with autophagosomes and the autophagy-related protein LC3 (MAP1LC3A/B/C) and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion (By similarity).|||Ubiquitinated; this does not lead to proteasomal degradation. May undergo both 'Lys-48'- and 'Lys-63'-linked polyubiquitination.|||autophagosome|||perinuclear region http://togogenome.org/gene/10090:Nedd1 ^@ http://purl.uniprot.org/uniprot/P33215 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Down-regulated during the development of brain.|||During mitosis, prior phosphorylation on Thr-550 by CDK1 promotes subsequent phosphorylation by PLK1 on Ser-397, Ser-426 and Ser-637. Phosphorylated NEDD1 can interact with gamma-tubulin for targeting the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation.|||Interacts with FAM29A. Interacts with HSPA1A and HSPA1B. Interacts with gamma-tubulin in a HSPA1A/B-dependent manner.|||May be due to intron retention.|||Required for mitosis progression. Promotes the nucleation of microtubules from the spindle (By similarity). May play an important role during the embryonic development and differentiation of the central nervous system (PubMed:1378265).|||centrosome http://togogenome.org/gene/10090:Camsap2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YY67|||http://purl.uniprot.org/uniprot/Q8C1B1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAMSAP1 family.|||Cytoplasm|||Golgi apparatus|||Interacts with CAMSAP3 (PubMed:23169647). Interacts with KATNA1 and KATNB1; leading to regulate the length of CAMSAP2-decorated microtubule stretches (By similarity). Interacts with a complex formed by AKAP9 and PDE4DIP isoform 2/MMG8/SMYLE, which recruits CAMSAP2 to the Golgi (By similarity). Interacts with MAPRE1/EB1 (By similarity).|||Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (By similarity). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (By similarity). In addition, it also reduces the velocity of microtubule polymerization (By similarity). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (By similarity). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (By similarity). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (By similarity). Through the microtubule cytoskeleton, regulates the autophagosome transport (By similarity).|||The CKK domain binds microtubules and specifically recognizes the minus-end of microtubules.|||The CKK domain binds microtubules.|||The MBD (microtubule-binding domain) region can recognize some features of the microtubule lattice, which might contribute to the specific decoration of growing microtubule minus-ends by CAMSAP2.|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Or6b2b ^@ http://purl.uniprot.org/uniprot/Q7TQS4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Evpl ^@ http://purl.uniprot.org/uniprot/Q9D952 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the plakin or cytolinker family.|||Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments.|||Cornified envelope|||May form a homodimer or a heterodimer with PPL.|||cytoskeleton|||desmosome http://togogenome.org/gene/10090:Lrrk1 ^@ http://purl.uniprot.org/uniprot/Q3UHC2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. ROCO subfamily.|||Binding of GTP stimulates kinase activity.|||Cytoplasm|||Expressed in osteoclasts and bone marrow stromal cells.|||Homodimer (By similarity). Interacts with CSK (PubMed:23526378).|||Knockout mice are born at the expected Mendelian ratio. At 4 weeks of age, their body length is slightly shorter than that of wild-type littermates. They progressively develop severe osteopetrosis, reduced bone resorption in endocortical and trabecular regions, and increased bone mineralization. Knockout animals have lifelong accumulation of bone, and females are resistant to ovariectomy-induced bone loss. Osteoclasts derived from mutant mice form a reduced area of resorption pits compared to controls, suggesting dysfunction of multinucleated osteoclasts. Osteoclast precursors differentiate into multinucleated cells, but fail to form peripheral sealing zones and ruffled borders, and do not resorb bone (PubMed:23526378, PubMed:27055475). These abnormalities are associated with changes in the SRC signaling pathway. This phenotype may be specific LRRK1 ablation, as knockout of the paralogous gene LRRK2 does not show any obvious bone phenotype (PubMed:23526378).|||Plays a role in the negative regulation of bone mass, acting through the maturation of osteoclasts. http://togogenome.org/gene/10090:Foxl3 ^@ http://purl.uniprot.org/uniprot/J3QP53 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Insl3 ^@ http://purl.uniprot.org/uniprot/Q5RL10 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the insulin family.|||Heterodimer of a B chain and an A chain linked by two disulfide bonds.|||Secreted|||Seems to play a role in testicular function. May be a trophic hormone with a role in testicular descent in fetal life. Is a ligand for LGR8 receptor. http://togogenome.org/gene/10090:Gm10228 ^@ http://purl.uniprot.org/uniprot/O09048 ^@ Similarity|||Subunit ^@ Belongs to the KRTAP type 6 family.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Slc2a7 ^@ http://purl.uniprot.org/uniprot/B1ARZ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.|||Cell membrane http://togogenome.org/gene/10090:Frg1 ^@ http://purl.uniprot.org/uniprot/P97376|||http://purl.uniprot.org/uniprot/Q78P92 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FRG1 family.|||Binds to mRNA in a sequence-independent manner. May play a role in regulation of pre-mRNA splicing or in the assembly of rRNA into ribosomal subunits. May be involved in mRNA transport. May be involved in epigenetic regulation of muscle differentiation through regulation of activity of the histone-lysine N-methyltransferase KMT5B.|||Cajal body|||Cytoplasm|||Homodimer and homotetramer in solution. Identified in the spliceosome C complex. Interacts (via N-terminus) with KPNA2 and NXF1/TAP. Interacts with F-actin with a stoichiometry of 2:1 (By similarity). Interacts with KMT5B (via C-terminus). Interacts with GARIN3, SMN1 and PABPN1 (By similarity).|||Overexpression of Frg1 leads to development of facioscapulohumeral muscular dystrophy (FSHD1)-like symptoms such as kyphosis, progressive muscle dystrophy and skeletal muscle atrophy. It also causes aberrant pre-mRNA splicing of Tnnt3 and Mtmr1, affects the localization and activity of KMT5B, and leads to increased levels of Eid3, resulting in inhibited muscle differentiation. These results suggest that human FSHD1 results from inappropriate overexpression of FRG1 which leads to abnormal alternative splicing of specific pre-mRNAs (PubMed:16341202, PubMed:23720823).|||Z line|||nucleolus http://togogenome.org/gene/10090:Arsb ^@ http://purl.uniprot.org/uniprot/A0A0R4J138|||http://purl.uniprot.org/uniprot/P50429 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Cell surface|||Homodimer.|||Inhibited by ethanol (By similarity).|||Lysosome|||Removes sulfate groups from chondroitin-4-sulfate (C4S) and regulates its degradation (By similarity). Involved in the regulation of cell adhesion, cell migration and invasion in colonic epithelium (By similarity). In the central nervous system, is a regulator of neurite outgrowth and neuronal plasticity, acting through the control of sulfate glycosaminoglycans and neurocan levels (By similarity).|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:C1ql3 ^@ http://purl.uniprot.org/uniprot/Q9ESN4 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Forms homooligomers. Interacts with ADGRB3 (PubMed:21262840). Forms heterooligomers with C1QL2 and C1QL4, when proteins are coexpressed; this interaction does not occur after secretion.|||Highly expressed in brain and white adipose tissue. In gonadal fat pad, expressed at lower levels in adipocytes than in the stromal vascular fraction (VSP), which contains preadipocytes, fibroblasts, endothelial cells and occasional immune cells. Expression exhibits sexually dimorphism, with higher levels in females than in males (at protein level). Tends to be up-regulated in adipose tissue from obese males, but not females. Expressed in glial cells.|||In adipocytes, up-regulated by rosiglitazone, an insulin-sensitizing drug.|||May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses. Plays a role in glucose homeostasis. Via AMPK signaling pathway, stimulates glucose uptake in adipocytes, myotubes and hepatocytes and enhances insulin-stimulated glucose uptake. In a hepatoma cell line, reduces the expression of gluconeogenic enzymes G6PC1 and PCK1 and hence decreases de novo glucose production.|||Secreted http://togogenome.org/gene/10090:Vmn1r117 ^@ http://purl.uniprot.org/uniprot/L7N2C9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dct ^@ http://purl.uniprot.org/uniprot/P29812 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tyrosinase family.|||Binds 2 Zn(2+) ions per subunit.|||Forms an OPN3-dependent complex with TYR in response to blue light in melanocytes.|||Glycosylated.|||Melanocytes and retinal pigmented epithelium (at protein level).|||Melanosome|||Melanosome membrane|||Mutant mice show an hypopigmentation of the coat and have the retinal pigmented epithelium significantly less pigmented than wild-type retinas.|||Plays a role in melanin biosynthesis (PubMed:33100333). Catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid (DHICA) (PubMed:1537333, PubMed:1537334).|||The slaty mutation in Tyrp2 leads to a decrease of DT activity and a consequent change in the pigmentation of the mice to a dark gray/brown eumelanin. The slaty-2j mutation has a similar phenotype, the slaty-lt (light) mutation has a more severe effect and is semidominant; its phenotype may be a result of the failure of the enzyme to be correctly targeted to its normal location on the inner face of the melanosomal membrane. http://togogenome.org/gene/10090:Bmp8a ^@ http://purl.uniprot.org/uniprot/P34821|||http://purl.uniprot.org/uniprot/Q3TZB2|||http://purl.uniprot.org/uniprot/Q80VZ0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||By dexamethasone in calvarial osteoblasts.|||Deletion mutant mice show normal embryonic and postnatal development. Homozygous mutant females have normal fertility. Males do not show germ cell defects during the initiation of spermatogenesis. However, germ cell degeneration is observed in about half of adult males.|||Expressed in testis. expressed in trophoblast cells of the labyrinthine region of the placenta and in the inner root sheath of hair follicles of early postnatal skin (PubMed:8843393). Expressed predominantly in the neonatal mouse spermatogonia (PubMed:28465413).|||Extensive expression found in 8-day embryos, fell drastically in 10-day embryos and virtually absent in 17-day embryos. Expressed during specific stages of spermatogenesis, with the highest levels in stage 6-8 round spermatids after 3 weeks of age.|||Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including spermatogenesis, osteogenesis, steroidogenesis as well as regulation of energy balance (PubMed:9463357, PubMed:12925636, PubMed:28465413). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A (By similarity). In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. In addition, activates the SMAD2/3 pathway (PubMed:28465413).|||Homodimer; disulfide-linked.|||Secreted http://togogenome.org/gene/10090:Vipas39 ^@ http://purl.uniprot.org/uniprot/Q8BGQ1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPE39 family.|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Interacts with VPS33B (By similarity). Associates with the homotypic fusion and vacuole protein sorting (HOPS) complex; impaired by VPS33B (By similarity). Interacts with RAB11A (PubMed:20190753).|||Late endosome|||Proposed to be involved in endosomal maturation implicating in part VPS33B. In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical RAB11A-dependent recycling pathway and in the maintenance of the apical-basolateral polarity (PubMed:20190753). May play a role in lysosomal trafficking, probably via association with the core HOPS complex in a discrete population of endosomes; the functions seems to be independent of VPS33B (By similarity). May play a role in vesicular trafficking during spermatogenesis (By similarity). May be involved in direct or indirect transcriptional regulation of E-cadherin.|||Recycling endosome|||Vipar-deficient inner medullary collecting duct cells display abnormal expression of membrane proteins such as Ceacam5, structural and functional tight junction defects and reduced E-cadherin expression. http://togogenome.org/gene/10090:Slco1b2 ^@ http://purl.uniprot.org/uniprot/Q9JJL3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A conserved histidine residue in the third TMD (His-113) may play an essential role in the pH sensitivity of SLCO1B2/OATP1B2-mediated substrate transport.|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Liver specific.|||Mediates the Na(+)-independent uptake of organic anions such as taurochlate, bromosulfophthalein and steroid conjugates (estrone 3-sulfate, 17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate). Also transports prostaglandin E2 and L-thyroxine (T4). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment. Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions. http://togogenome.org/gene/10090:Ces1d ^@ http://purl.uniprot.org/uniprot/Q8VCT4 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||By di-(2-ethylhexyl) phthalate.|||Endoplasmic reticulum lumen|||Highest expression occurs in liver with lower levels in adipose tissue, kidney, heart, intestine, lung, testis and thymus.|||Homotrimer.|||Lipid droplet|||Major lipase in white adipose tissue. Involved in the metabolism of xenobiotics and of natural substrates. Hydrolyzes triacylglycerols and monoacylglycerols, with a preference for monoacylglycerols. The susceptibility of the substrate increases with decreasing acyl chain length of the fatty acid moiety. Catalyzes the synthesis of fatty acid ethyl esters (PubMed:15220344). Hydrolyzes retinyl esters (By similarity).|||Microsome|||Was originally thought to originate from human.|||cytosol http://togogenome.org/gene/10090:Sod1 ^@ http://purl.uniprot.org/uniprot/P08228 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 40% reduction in hepatic GPX1 activity.|||Belongs to the Cu-Zn superoxide dismutase family.|||Binds 1 copper ion per subunit.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Destroys radicals which are normally produced within the cells and which are toxic to biological systems.|||Homodimer; non-disulfide-linked (PubMed:20727846). Heterodimer with SOD1. The heterodimer CCS:SOD1 interacts with SLC31A1; this heterotrimer is Cu(1+)-mediated and its maintenance is regulated through SOD1 activation (By similarity).|||Nucleus|||Palmitoylation helps nuclear targeting and decreases catalytic activity.|||Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity. http://togogenome.org/gene/10090:Dbnl ^@ http://purl.uniprot.org/uniprot/Q62418 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis. Plays a role in the reorganization of the actin cytoskeleton, formation of cell projections, such as neurites, in neuron morphogenesis and synapse formation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for the formation of organized podosome rosettes. May act as a common effector of antigen receptor-signaling pathways in leukocytes. Acts as a key component of the immunological synapse that regulates T-cell activation by bridging TCRs and the actin cytoskeleton to gene activation and endocytic processes.|||Belongs to the ABP1 family.|||Cell membrane|||Detected in hippocampus neurons and in the Purkinje cell layer in cerebellum (at protein level). Predominantly expressed in brain, thymus and spleen. Also found in testis, heart and lung. Little or no expression detected in ovary or muscle.|||Early endosome|||Golgi apparatus membrane|||In the embryo, expression is high during early development but drops during later development.|||Interacts with SHANK3, SYN1 and PRAM1 (By similarity). Interacts with SHANK2. Interacts with FGD1, DNM1 and MAP4K1. Interacts with ANKRD54. Interacts with COBL. Interacts with WASL and WIPF1.|||Perikaryon|||Postsynaptic density|||Synapse|||The SH3 domain mediates interaction with SHANK2, SHANK3 and PRAM1.|||cell cortex|||clathrin-coated vesicle membrane|||cytoskeleton|||cytosol|||dendrite|||lamellipodium|||neuron projection|||podosome|||ruffle http://togogenome.org/gene/10090:Maip1 ^@ http://purl.uniprot.org/uniprot/Q8BHE8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with AFG3L2 (PubMed:27642048). Interacts with SPG7 (By similarity). Interacts with SMDT1/EMRE (via the N-terminal transit peptide); interaction is direct and takes place before maturation of SMDT1/EMRE (By similarity).|||Mitochondrion matrix|||Promotes sorting of SMDT1/EMRE in mitochondria by ensuring its maturation. Interacts with the transit peptide region of SMDT1/EMRE precursor protein in the mitochondrial matrix, leading to protect it against protein degradation by YME1L1, thereby ensuring SMDT1/EMRE maturation by the mitochondrial processing peptidase (PMPCA and PMPCB). http://togogenome.org/gene/10090:Prdm5 ^@ http://purl.uniprot.org/uniprot/E9Q707|||http://purl.uniprot.org/uniprot/Q9CXE0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Interacts with EHMT2/G9A, GFI1 and HDAC1.|||Nucleus|||Sequence-specific DNA-binding transcription factor. Represses transcription at least in part by recruitment of the histone methyltransferase EHMT2/G9A and histone deacetylases such as HDAC1. Regulates hematopoiesis-associated protein-coding and microRNA (miRNA) genes (By similarity). May regulate the expression of proteins involved in extracellular matrix development and maintenance, connective tissue components and molecules regulating cell migration and adhesion. May cause G2/M arrest and apoptosis in cancer cells (By similarity). http://togogenome.org/gene/10090:Srpr ^@ http://purl.uniprot.org/uniprot/Q9DBG7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTP-binding SRP family.|||Component of the SRP (signal recognition particle) receptor (By similarity). Ensures, in conjunction with the signal recognition particle, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (By similarity). Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SRP subunit SRP54 (By similarity). SRP receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (By similarity).|||Endoplasmic reticulum membrane|||Heterodimer with SRPRB (By similarity). Interacts with the signal recognition particle (SRP) complex subunit SRP54 (By similarity).|||The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the signal recognition particle (SRP) complex subunit SRP54 (By similarity). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (By similarity). GTPase induced rearrangement of SR drives SRP-mediated cotranslational protein translocation into the ER (By similarity). http://togogenome.org/gene/10090:Higd2a ^@ http://purl.uniprot.org/uniprot/Q9CQJ1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with cytochrome c oxidase (COX, complex IV); proposed complex component.|||Mitochondrion inner membrane|||Mitochondrion membrane|||Proposed subunit of cytochrome c oxidase (COX, complex IV), which is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. May be involved in cytochrome c oxidase activity. May play a role in the assembly of respiratory supercomplexes (By similarity). http://togogenome.org/gene/10090:Ncald ^@ http://purl.uniprot.org/uniprot/Q91X97 ^@ Function|||Similarity|||Subunit ^@ Belongs to the recoverin family.|||Interacts with GUCY2D.|||May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions (By similarity). http://togogenome.org/gene/10090:Chmp1a ^@ http://purl.uniprot.org/uniprot/Q921W0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF7 family.|||Cytoplasm|||Endosome membrane|||Highly expressed in adult heart, kidney and liver. Expressed at lower levels in adult colon, spleen, lung, brain, testis and muscle. Also expressed in myoblasts and embryo fibroblasts.|||Nucleus matrix|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing (By similarity).|||Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Self-associates. Interacts with CHMP1B. Interacts with VPS4A. Interacts with VPS4B. Interacts with PHF1. Interacts with IST1. Interacts with MITD1 (By similarity). http://togogenome.org/gene/10090:Vmn1r65 ^@ http://purl.uniprot.org/uniprot/Q9EPS7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H2al1j ^@ http://purl.uniprot.org/uniprot/A2BFR3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Tmprss9 ^@ http://purl.uniprot.org/uniprot/D3YTR8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Serase-1 and serase-2 are serine proteases that hydrolyze the peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln-Gly-Arg-AMC. In contrast, N-t-Boc-Ala-Phe-Lys-AMC and N-t-Boc-Ala-Pro-Ala-AMC are not significantly hydrolyzed. http://togogenome.org/gene/10090:Stom ^@ http://purl.uniprot.org/uniprot/P54116 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the band 7/mec-2 family.|||Cell membrane|||Cytoplasmic vesicle|||Expressed in all sensory neurons of the dorsal root ganglia. In the CNS, expressed in many neurons of the spinal cord, medulla and pons. Expressed only in scattered neurons in the cortex, hippocampus, thalamus and basal ganglia. In the cerebellum, expressed in all Purkinje cells (at protein level). Widely expressed with high levels in heart, liver, skeletal muscle and testis and low levels in lung, brain and spleen.|||First expressed in the developing embryo at 11.5 dpc when target innervation is complete. Expression continues into adulthood.|||Interacts with LANCL1 (By similarity). Interacts with SLC2A1 (By similarity). Interacts with SLC4A1; this interaction positively regulates SLC4A1 activity (By similarity). Identified in large complexes with SLC40A1, SLC14A1, SLC29A1 and AQP1 (By similarity). Homodimer and higher order homooligomers (By similarity). The homodimer is banana-shaped (By similarity). Interacts with ASIC1, ASIC2 and ASIC3 (PubMed:15471860, PubMed:22850675). Interacts with STOML1; may redistribute STOM from the plasma membrane to late endosomes (By similarity).|||Melanosome|||Membrane raft|||Regulates ion channel activity and transmembrane ion transport. Regulates ASIC2 and ASIC3 channel activity.|||cytoskeleton http://togogenome.org/gene/10090:Ckm ^@ http://purl.uniprot.org/uniprot/A2RTA0|||http://purl.uniprot.org/uniprot/P07310 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP:guanido phosphotransferase family.|||Cytoplasm|||Dimer of identical or non-identical chains, which can be either B (brain type) or M (muscle type). With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain.|||Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. http://togogenome.org/gene/10090:Rnf128 ^@ http://purl.uniprot.org/uniprot/Q9D304 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ At 6.0 dpc, expressed in both the extraembryonic endoderm and extraembryonic ectoderm. After the beginning of gastrulation, expression remains extraembryonic, and is mostly confined to the visceral endoderm. At 8.5 dpc, expression appears within the mesodermally derived allantois, and is highly expressed in the epithelial layer of the yolk sac. At 9.5 dpc, expressed in the hindgut and adjoining yolk sac. At stage 10 dpc, appears to be widely expressed throughout the embryo with higher expression within the branchial arches and within intersomitic endothelial cells.|||Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination.|||Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain.|||E3 ubiquitin-protein ligase that catalyzes 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains formation. Functions as an inhibitor of cytokine gene transcription. Inhibits IL2 and IL4 transcription, thereby playing an important role in the induction of the anergic phenotype, a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of interleukin production. Ubiquitinates ARPC5 with 'Lys-48' linkages and COR1A with 'Lys-63' linkages leading to their degradation, down-regulation of these cytosleletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals (By similarity).|||Endomembrane system|||Expressed in brain, kidney, heart, liver, ovary, testis and thymus. Expression increased as early as 4 hours by 5- to 7-fold in anergized cultures as compared to resting or activated cells.|||Induced under anergic conditions. Up-regulated during T-cell anergy induction following signaling through the T-cell antigen receptor.|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Clec10a ^@ http://purl.uniprot.org/uniprot/P49300 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in 7 dpc, 11 dpc, 15 dpc and 17 dpc embryo.|||Detected in lymph node in the subcapsular sinus, interfollicular regions, T and B-cell boundary and in the areas surrounding high endothelial venules (at protein level). Expressed on the surface of activated macrophages. Expressed in heart, lung, testis, skeletal muscle, spleen, brain, kidney and thymus. Expressed in P388, RAW 264.7 and M1 cell lines.|||Homooligomer. Interacts with SIGLEC1, which may act as a counter-receptor for CLEC10A in lymph node.|||Membrane|||Recognizes terminal galactose and N-acetylgalactosamine units. May participate in the interaction between tumoricidal macrophages and tumor cells. Plays a role in the recruitment of inflammatory monocytes to adipose tissue in diet-induced obesity. http://togogenome.org/gene/10090:Tmem97 ^@ http://purl.uniprot.org/uniprot/Q8VD00 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM97/sigma-2 receptor family.|||Interacts with NPC1.|||Intracellular orphan receptor that binds numerous drugs and which is highly expressed in various proliferating cells. Corresponds to the sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation. May play a role as a regulator of cellular cholesterol homeostasis. May function as sterol isomerase. May alter the activity of some cytochrome P450 proteins.|||Nucleus membrane|||Rough endoplasmic reticulum membrane|||Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile. Sigma-2 receptors are identified by radioligand-binding studies as a binding site with high affinity for di-o-tolylguanidine (DTG) and haloperidol. http://togogenome.org/gene/10090:Zic5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0E2|||http://purl.uniprot.org/uniprot/Q7TQ40 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GLI C2H2-type zinc-finger protein family.|||Essential for neural crest development, converting cells from an epidermal fate to a neural crest cell fate. Binds to DNA.|||Expressed in the embryonic ectoderm before gastrulation, and gradually restricted to the anterior part from the mid to late streak stage. Becomes restricted to the dorsal side of the neural tube at 8 dpc. After neural tube closure, is expressed in the dorsal midline of the entire neural tube and in the roof plate. Also expressed in the developing limb buds.|||Mice exhibited insufficient neural tube closure at the rostral end and malformation of neural-crest-derived facial bones especially the mandible. After birth, mice were significantly smaller than their littermates and most of them died within 2 months.|||Nucleus http://togogenome.org/gene/10090:Rtf1 ^@ http://purl.uniprot.org/uniprot/A2AQ19 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. Binds single-stranded DNA (By similarity). Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex.|||Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and WDR61. The PAF1 complex interacts with PHF5A (PubMed:27749823).|||It is uncertain whether Met-1 or Met-46 is the initiator.|||The Plus3 domain mediates single-stranded DNA-binding.|||nucleoplasm http://togogenome.org/gene/10090:Or10ab5 ^@ http://purl.uniprot.org/uniprot/Q8VF20 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nudt8 ^@ http://purl.uniprot.org/uniprot/Q9CR24 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acyl-CoA diphosphatase that mediates the hydrolysis of a wide range of CoA and CoA esters yielding 3',5'-ADP and the corresponding 4'-phosphopantetheine derivative as products (PubMed:31004344). Hydrolyzes short- and medium-chain acyl-CoAs, exhibiting the highest activity toward free CoA, hexanoyl-CoA, and octanoyl-CoA and the lowest activity against acetyl-CoA (PubMed:31004344). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (PubMed:32432673).|||Belongs to the Nudix hydrolase family.|||Expressed at the highest levels in the kidneys, heart, brown adipose tissue and liver (at protein level) (PubMed:31004344). Expressed at lower levels in the brain, skeletal muscle, and white adipose tissue (at protein level) (PubMed:31004344).|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Or1s2 ^@ http://purl.uniprot.org/uniprot/B9EHG2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Olfm1 ^@ http://purl.uniprot.org/uniprot/G3X9Q7|||http://purl.uniprot.org/uniprot/O88998|||http://purl.uniprot.org/uniprot/Q8R357 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contributes to the regulation of axonal growth in the embryonic and adult central nervous system by inhibiting interactions between RTN4R and LINGO1. Inhibits RTN4R-mediated axon growth cone collapse (PubMed:22923615). May play an important role in regulating the production of neural crest cells by the neural tube (By similarity). May be required for normal responses to olfactory stimuli (PubMed:26107991).|||Endoplasmic reticulum|||Expressed in the brain cortex, olfactory bulb and vomeronasal neuroepithelium (at protein level) (PubMed:9473566, PubMed:26107991, PubMed:22923615, PubMed:22632720). Detected in brain cortex, hippocampus, dorsal root ganglion and olfactory bulb (PubMed:9473566, PubMed:22923615).|||Expression increases moderately during embryonic development and remains stable in the postnatal brain (PubMed:21228389). Highly expressed in uterus luminal epithelium after embryo implantation (PubMed:26107991).|||Females have slightly lower body weight than wild-type at birth, but strongly reduced body weight one to eight weeks after birth. Mutant females do not display normal estrus cycle responses to male odor, and have very low fertility due to a strongly decreased rate of ovulation and a low mating rate.|||Homotetramer; disulfide-linked. Dimer of dimers, giving rise to a V-shaped homotretramer (PubMed:25903135). Isoform 1 and isoform 3 interact with RTN4R (PubMed:22923615). Identified in a complex with RTN4R and LINGO1 (PubMed:22923615). Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including OLFM1. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (PubMed:22632720). Interacts with OLFM2 (By similarity). Interacts with DTNB (PubMed:17265465).|||Perikaryon|||Secreted|||Synapse|||The protein contains a globular N-terminal tetramerization domain, a long stalk formed by the coiled coil region and a C-terminal olfactomedin-like domain. Interactions between dimers are mediated by the coiled coil region. The dimers interact mostly via the N-terminal tetramerization domain, giving rise to a V-shaped overall architecture of the tetramer.|||The protein structure is stabilized by calcium ions.|||axon http://togogenome.org/gene/10090:Fmo4 ^@ http://purl.uniprot.org/uniprot/Q8VHG0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Microsome membrane|||This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. http://togogenome.org/gene/10090:Grik4 ^@ http://purl.uniprot.org/uniprot/Q8BMF5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK4 subfamily.|||Cell membrane|||Forms a heteromeric channel with GRIK1 or GRIK3.|||Postsynaptic cell membrane|||Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > glutamate >> AMPA (By similarity). http://togogenome.org/gene/10090:Trappc10 ^@ http://purl.uniprot.org/uniprot/Q3TLI0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAPPC10 family.|||Gene-null mice have smaller total brain area compared to wild-type animals, with specific reductions in the size of the corpus callosum, regions of the hippocampus, anterior commissure, and internal capsule. Only white matter structures are affected in mutant mice. There is a loss of myelination in these regions, but oligodendrocyte numbers are normal.|||Specific component of the multisubunit TRAPP II complex, which includes at least TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, TRAPPC6A/B, TRAPPC9, TRAPPC10 and TRAPPC14. TRAPPC9, TRAPPC10 and TRAPPC14 are specific subunits of the TRAPP II complex (PubMed:19656848). Interacts with TRAPPC14 (By similarity).|||Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether.|||cis-Golgi network http://togogenome.org/gene/10090:Sf3a3 ^@ http://purl.uniprot.org/uniprot/Q58E59|||http://purl.uniprot.org/uniprot/Q9D554 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SF3A3 family.|||Component of splicing factor SF3A which is composed of three subunits; SF3A3/SAP61, SF3A2/SAP62 and SF3A1/SAP114. SF3A1 functions as scaffold that interacts directly with both SF3A2 and SF3A3. SF3A associates with the splicing factor SF3B and a 12S RNA unit to form the mature 17S U2 small nuclear ribonucleoprotein complex (17S U2 snRNP). Identified in the spliceosome 'E' complex, a precursor of the spliceosome 'A' complex. Identified in the spliceosome 'A' and 'B' complexes. Identified in the spliceosome 'C' complex.|||Involved in pre-mRNA splicing as a component of the splicing factor SF3A complex that contributes to the assembly of the 17S U2 snRNP, and the subsequent assembly of the pre-spliceosome 'E' complex and the pre-catalytic spliceosome 'A' complex. Involved in pre-mRNA splicing as a component of pre-catalytic spliceosome 'B' complexes.|||Nucleus http://togogenome.org/gene/10090:Nme2 ^@ http://purl.uniprot.org/uniprot/Q01768|||http://purl.uniprot.org/uniprot/Q5NC82 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NDK family.|||Cytoplasm|||Expressed in the base region of the oxyntic and pyloric mucosae.|||Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6) (By similarity). Interacts with CAPN8 (PubMed:16476741). Interacts with AKAP13 (By similarity). Interacts with ITGB1BP1 (via C-terminal domain region) (By similarity). Interacts with BCL2L10 (PubMed:17532299).|||Impaired activation of the K(+) channel Kcnn4, resulting in defective T-cell activation.|||Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically. Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not. Exhibits histidine protein kinase activity (By similarity).|||Nucleus|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Sdad1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B7|||http://purl.uniprot.org/uniprot/Q80UZ2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SDA1 family.|||Required for 60S pre-ribosomal subunits export to the cytoplasm.|||nucleolus http://togogenome.org/gene/10090:Lrp4 ^@ http://purl.uniprot.org/uniprot/Q8VI56 ^@ Disease Annotation|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LDLR family.|||Cell membrane|||Defects in Lrp4 are the cause of digitation anormale (dan) phenotype, this mutation is the consequence of a retroviral insertion. Dan mice shown growth retardation in 10-day-old mice dan/dan and polysyndactyly (PubMed:16517118). Defects in Lrp4 are the cause of malformed digits (mdig) phenotype. It is a spontaneous, autosomal recessive mutation resulting in polysyndactyly (PubMed:16517118).|||Homooligomer. Interacts with MUSK; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK. Interacts (via the extracellular domain) with SOST; the interaction facilitates the inhibition of Wnt signaling (By similarity). Interacts with MESD; the interaction promotes glycosylation of LRP4 and its cell-surface expression (PubMed:24140340).|||Intron retention.|||Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Alternatively, may be involved in the negative regulation of the canonical Wnt signaling pathway, being able to antagonize the LRP6-mediated activation of this pathway. More generally, has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes. Plays an essential role in the process of digit differentiation (PubMed:16517118).|||N-glycosylation is required for cell surface location. http://togogenome.org/gene/10090:Amy1 ^@ http://purl.uniprot.org/uniprot/P00687 ^@ Cofactor|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 13 family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 1 Cl(-) ion per subunit.|||Expressed in liver and saliva.|||Hepatic and salivary alpha-amylases are encoded by the same gene; however, their mRNAs have different 5'-UTR sequences.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Prl3a1 ^@ http://purl.uniprot.org/uniprot/Q78Y73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Rigi ^@ http://purl.uniprot.org/uniprot/A1L0V6|||http://purl.uniprot.org/uniprot/Q6Q899 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. RLR subfamily.|||By interferon (IFN).|||Cytoplasm|||Death between 12.5 dpc and 14 dpc due to liver apoptosis. Those who are born alive show growth retardation and die within 3 weeks.|||Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes RIGI recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagic degradation.|||ISGylated. Conjugated to ubiquitin-like protein ISG15 upon IFN-beta stimulation. ISGylation negatively regulates its function in antiviral signaling response.|||Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons. Ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Sendai virus (SeV), Rhabdoviridae and Flaviviridae. It also detects rotavirus and orthoreovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome. Detects dsRNA produced from non-self dsDNA by RNA polymerase III. May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.|||Monomer; maintained as a monomer in an autoinhibited state. Upon binding of viral RNAs and conformational shift, homooligomerizes and forms filaments on these molecules. Interacts (via tandem CARD domain) with MAVS/IPS1 promoting its filamentation. Interacts with DHX58/LGP2, IKBKE, TBK1 and STING1. Interacts (via CARD domain) with TRIM25 (via SPRY domain). Interacts (double-stranded RNA-bound oligomeric form) with RNF135 (homodimer); involved in RNA length-dependent activation of the RIG-I signaling pathway. Interacts with CYLD. Interacts with NLRC5; blocks the interaction of MAVS/IPS1 to RIGI. Interacts with SRC. Interacts with DDX60. Interacts with ZC3HAV1 (via zinc-fingers) in an RNA-dependent manner. Interacts (via tandem CARD domain) with SEC14L1; the interaction is direct and impairs the interaction of RIGI with MAVS/IPS1. Interacts with VCP/p97; interaction is direct and allows the recruitment of RNF125 and subsequent ubiquitination and degradation. Interacts with NOP53; may regulate RIGI through USP15-mediated 'Lys-63'-linked deubiquitination (By similarity). Interacts with SIGLEC10, CBL and PTPN11; within a negative feedback loop leading to RIGI degradation (PubMed:23374343). Interacts with LRRC25. Interacts with ZCCHC3; leading to activation of RIGI. Interacts with RNF123 (By similarity). Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated ubiquitination of RIGI and activation of the RIG-I signaling pathway (By similarity). Interacts with IFIT3 (By similarity). Interacts with DDX3X (By similarity). Interacts with RTN3 (By similarity). Interacts with ARL16; this interaction is GTP-dependent and induced upon viral infection; this interaction suppresses the RNA sensing activity of RIGI (By similarity). Interacts with DHX16; this interaction enhances RIGI-mediated antiviral response (By similarity). Interacts with Irgm1; promoting RIGI degradation (By similarity). Interacts with IFI6; this interaction inhibits RIGI activation (By similarity).Interacts with ECSIT; this interaction bridges RIGI to the MAVS complex at the mitochondrion (By similarity).|||Phosphorylated in resting cells and dephosphorylated in RNA virus-infected cells. Phosphorylation at Thr-771 results in inhibition of its activity while dephosphorylation at these sites results in its activation.|||Sumoylated, probably by MUL1; inhibiting its polyubiquitination.|||The 2 CARD domains are responsible for interaction with and signaling through MAVS/IPS1 and for association with the actin cytoskeleton.|||The RLR CTR domain controls homooligomerization and interaction with MAVS/IPS1. In the absence of viral infection, the protein is maintained as a monomer in an autoinhibited state with the CARD domains masked through intramolecular interactions with the RLR CTR domain. Upon binding to viral RNA and ubiquitination by RNF135, a conformational change releases the autoinhibition promoting further homooligomerization, interaction of the CARD domains with the adapter protein MAVS/IPS1 and activation of the downstream RIG-I signaling pathway.|||The helicase domain is responsible for dsRNA recognition.|||The second CARD domain is the primary site for 'Lys-63'-linked ubiquitination.|||Ubiquitinated. 'Lys-63' ubiquitination by RNF135, which occurs after RNA-binding and homodimerization, releases the autoinhibition of the CARD domains by the RLR CTR domain, an essential step in the activation of the RIG-I signaling pathway. Also ubiquitinated by TRIM4. Also undergoes 'Lys-48' ubiquitination by RNF125 that leads to proteasomal degradation. 'Lys-48' ubiquitination follows viral infection and is enhanced by 'Lys-63'-linked ubiquitination of the CARD domains that promotes interaction with VCP/p97 and subsequent recruitment of RNF125 (By similarity). Within a negative feedback loop involving SIGLEC10 and PTPN11, 'Lys-48' ubiquitination at Lys-813 by CBL also elicits the proteasomal degradation of RIGI (PubMed:23374343). Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains. Also probably deubiquitinated by USP17L2/USP17 that cleaves 'Lys-48'- and 'Lys-63'-linked ubiquitin chains and positively regulates the receptor (By similarity). Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal degradation (By similarity). Deubiquitinated by USP27X that cleaves 'Lys-63'-linked ubiquitin chains and inhibits the innate immune receptor activity (By similarity).|||cytoskeleton|||ruffle membrane|||tight junction http://togogenome.org/gene/10090:Lyplal1 ^@ http://purl.uniprot.org/uniprot/E9QLB2|||http://purl.uniprot.org/uniprot/Q3UFF7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.|||Cytoplasm|||Has depalmitoylating activity toward KCNMA1. Does not exhibit phospholipase nor triacylglycerol lipase activity, able to hydrolyze only short chain substrates due to its shallow active site (By similarity). http://togogenome.org/gene/10090:Ccny ^@ http://purl.uniprot.org/uniprot/Q8BGU5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family. Cyclin Y subfamily.|||Cell membrane|||Detected in brain, heart, lung, skeletal muscle, ovary, thymus and testis (at protein level).|||Found in a complex with CAPRIN2, LRP6 and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus (By similarity). Interacts with CDK14 (By similarity). Interacts with CDK16 (PubMed:22184064). Interacts with LRP6 (By similarity).|||Heavily phosphorylated. Phosphorylation at Ser-71 and Ser-73 by CDK14 is enhanced during the G2 and M cell cycle phases, and creates a phosphodegron triggering SCF-dependent ubiquitination.|||Positive regulatory subunit of the cyclin-dependent kinase CDK14/PFTK1. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6, leading to the activation of the Wnt signaling pathway (By similarity). Recruits CDK16 to the plasma membrane (By similarity). Positive regulatory subunit of the cyclin-dependent kinase CDK16.|||Ubiquitinated; leading to its degradation. http://togogenome.org/gene/10090:Lamc1 ^@ http://purl.uniprot.org/uniprot/F8VQJ3 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||basement membrane http://togogenome.org/gene/10090:Gm4567 ^@ http://purl.uniprot.org/uniprot/Q3UTA8 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Pimreg ^@ http://purl.uniprot.org/uniprot/Q8BFY7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During mitosis, may play a role in the metaphase-to-anaphase transition.|||Interacts with PICALM; this interaction may target PICALM to the nucleus. During mitosis, associates with HDAC2 and MTA2 subunits of the chromatin-remodeling NuRD complex; this association is strongest at prometaphase and decreases as the cell progresses through metaphase and anaphase.|||Mainly expressed in thymus and ovary. Expressed in all T-cell subpopulations isolated from the thymus, macrophages, pro-erythrocytes, granulocytes, mast cells and progenitor cells.|||Nucleus|||The N-terminal destruction box 2 (D-box 2) is required for APC/C ubiquitination and proteasomal degradation.|||Ubiquitinated by the anaphase-promoting complex/cyclosome (APC/C) complex in the presence of FZR1, leading to its degradation by the proteasome during mitotic exit. However, degradation is not essential for normal mitotic progression within a single cell cycle (By similarity).|||Widely expressed at 9.5 dpc, including high levels in the neural tube, somites, the posterior region of the midbrain, olfactory placode and the branchial arches. At 10.5 dpc, reduction of the widespread expression and stronger expression in the neural tube, branchial arches, developing limbs, telencephalon, nasal process, lense vesicle, anterior and posterior regions of the mid- and hindbrain. From 11.5 dpc on, strongly expressed in the genital tubercle and hair and vibrissae follicles. From 12.5 dpc onwards, expression decreases, with a complete lack of expression in the cephalic region and the neural tube at 14.5 dpc. Strongly expressed during limb development, with higher levels in hindlimbs compared to forelimbs and expression slightly more marked in the posterior region of the limb buds. At 11.5 and 12.5 dpc, detected at the distal domain and the underlying mesenchyme, but not in the apical ectodermal ridge. Distally, becomes confined to the digits at 13.5 and 14.5 dpc.|||nucleolus http://togogenome.org/gene/10090:Abcb5 ^@ http://purl.uniprot.org/uniprot/B5X0E4|||http://purl.uniprot.org/uniprot/Q3UT27 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.|||Cell membrane|||Defects in corneal development. While eyes contain all anterior and posterior segment components, corneas show developmental abnormalities characterized by decreased cellularity of the apical epithelial layer and disorganized basal and wing cell layers. Defects are due to depletion of quiescent limbal stem cells, leading to enhanced proliferation and apoptosis, and resulting in defective corneal differentiation and wound healing.|||Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (By similarity). Specifically present in limbal stem cells, where it plays a key role in corneal development and repair (PubMed:25030174).|||In developing eye, expressed in basal limbal epithelium but not in central cornea. Acts as a marker of limbal stem cells.|||Membrane http://togogenome.org/gene/10090:Or5k16 ^@ http://purl.uniprot.org/uniprot/F8VQ90 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Morn5 ^@ http://purl.uniprot.org/uniprot/Q9DAI9 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in testis at 21 days after birth and expression is maintained (PubMed:28742876). Expressed in mature sperm (PubMed:28742876).|||Only detected in testis (at protein level).|||flagellum http://togogenome.org/gene/10090:Nkain4 ^@ http://purl.uniprot.org/uniprot/Q9JMG4 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKAIN family.|||Cell membrane|||Interacts with ATP1B1.|||Ubiquitous. Expressed in multiple regions of the brain such as cerebral cortex, thalamus, hippocampus, olfactory bulb and brainstem as well as in cerebellum with low expression in granular cell layer. http://togogenome.org/gene/10090:Nkx2-5 ^@ http://purl.uniprot.org/uniprot/P42582|||http://purl.uniprot.org/uniprot/Q3UQU2 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NK-2 homeobox family.|||Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, fetal and adult hearts. It is also expressed laterally in future pharyngeal endoderm which is believed to produce the heart inducer. After foregut closure expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium a derivative of the pharyngeal floor continues to express the protein after its levels diminish in the rest of the pharynx.|||Homodimer (via the homeobox); binds DNA as homodimer. Interacts (via the homeobox) with TBX5 (via the T-box); this complex binds DNA (By similarity). Interacts with HIPK1 and HIPK2, but not HIPK3 (PubMed:9748262). Interacts with the C-terminal zinc finger of GATA4 through its homeobox domain (PubMed:9584153). Also interacts with JARID2 which represses its ability to activate transcription of ANF (PubMed:15542826). Interacts with FBLIM1 (PubMed:14757752). Interacts with TBX18 (PubMed:17584735). Interacts with histone methyltransferase NSD2 (via HMG box) (PubMed:19483677). Interacts with NEDD9 (By similarity). Interacts with TBX1 (PubMed:16556915).|||Nucleus|||Predominantly in the adult and embryonic heart, and to a lesser extent in lingual muscle, spleen and stomach.|||The homeobox domain binds to double-stranded DNA.|||Transcription factor required for the development of the heart and the spleen (PubMed:9584153, PubMed:16556915, PubMed:19483677, PubMed:22560297). During heart development, acts as a transcriptional activator of NPPA/ANF in cooperation with GATA4 (PubMed:9584153). May cooperate with TBX2 to negatively modulate expression of NPPA/ANF in the atrioventricular canal (PubMed:12023302). Binds to the core DNA motif of NPPA promoter (PubMed:19483677). Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression (PubMed:22560297). Positively regulates transcription of genes such as COL3A1 and MMP2, resulting in increased pulmonary endothelial fibrosis in response to hypoxia (By similarity). http://togogenome.org/gene/10090:Fads6 ^@ http://purl.uniprot.org/uniprot/Q80UG1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the fatty acid desaturase type 1 family.|||Membrane http://togogenome.org/gene/10090:Ermp1 ^@ http://purl.uniprot.org/uniprot/Q3UVK0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M28 family.|||Binds 2 Zn(2+) ions per subunit.|||Endoplasmic reticulum membrane|||Within the ovary, required for the organization of somatic cells and oocytes into discrete follicular structures. http://togogenome.org/gene/10090:Or8h7 ^@ http://purl.uniprot.org/uniprot/A2AVA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cldn22 ^@ http://purl.uniprot.org/uniprot/Q9D7U6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Eefsec ^@ http://purl.uniprot.org/uniprot/Q9JHW4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. SelB subfamily.|||Cytoplasm|||Nucleus|||Translation factor necessary for the incorporation of selenocysteine into proteins. It probably replaces EF-Tu for the insertion of selenocysteine directed by the UGA codon. SelB binds GTP and GDP. http://togogenome.org/gene/10090:Cyp3a57 ^@ http://purl.uniprot.org/uniprot/D3YYZ0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Ccdc113 ^@ http://purl.uniprot.org/uniprot/Q8C5T8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of centriolar satellites contributing to primary cilium formation.|||Interacts with HAP1 and PCM1.|||centriolar satellite http://togogenome.org/gene/10090:Rwdd1 ^@ http://purl.uniprot.org/uniprot/Q9CQK7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the RWDD1/GIR2 family.|||Interacts with androgen receptor (By similarity). Interacts with DRG2.|||Protects DRG2 from proteolytic degradation. http://togogenome.org/gene/10090:Dtd2 ^@ http://purl.uniprot.org/uniprot/Q8BHA3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-151.|||Belongs to the DTD family.|||Cytoplasm|||Deacylates mischarged D-aminoacyl-tRNAs. Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS. Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids. Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr). By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality. In contrast to DTD1, deacylates L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase AARS. Can deacylate L-Ala due to a relaxed specificity for substrate chirality caused by the trans conformation of the Gly-Pro motif in the active site. Also hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) in vitro, although in vivo EEF1A1/EF-Tu may protect cognate achiral glycyl-tRNA(Gly) from DTD2-mediated deacetylation.|||Homodimer. http://togogenome.org/gene/10090:Mdh2 ^@ http://purl.uniprot.org/uniprot/P08249 ^@ Activity Regulation|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is enhanced after treatment either with trichostin A (TCA) or with nicotinamide (NAM) with the appearance of tri- and tetraacetylations. Glucose also increases acetylation (By similarity). Acetylation of Lys-239 and Lys-314 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the LDH/MDH superfamily. MDH type 1 family.|||Enzyme activity is enhanced by acetylation.|||Homodimer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Epb41l4a ^@ http://purl.uniprot.org/uniprot/P52963 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Brain, heart, lung, liver and spleen. Not detected in thymus and kidney.|||cytoskeleton http://togogenome.org/gene/10090:Phlpp2 ^@ http://purl.uniprot.org/uniprot/Q8BXA7 ^@ Activity Regulation|||Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 2 manganese ions per subunit. Mn(2+) is inhibitory below pH 8 and activating above pH 8 (By similarity).|||Cytoplasm|||Expressed in the retina.|||Inhibited by AKT1, AKT2 and AKT3. Activated by oleic acid and arachidonic acid.|||Interacts with AKT1, AKT3 and PRKCB. Interacts with STK4, RPS6KB1, RAF1. Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP2 and Akt. Interacts with NHERF1; NHERF1 scaffolds a heterotrimeric complex with PTEN (By similarity).|||Membrane|||Nucleus|||Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (By similarity). http://togogenome.org/gene/10090:Atp11a ^@ http://purl.uniprot.org/uniprot/E9Q3G7|||http://purl.uniprot.org/uniprot/P98197 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane (By similarity). Does not show flippase activity toward phosphatidylcholine (PC) (By similarity). Contributes to the maintenance of membrane lipid asymmetry with a specific role in morphogenesis of muscle cells. In myoblasts, mediates PS enrichment at the inner leaflet of plasma membrane, triggering PIEZO1-dependent Ca2+ influx and Rho GTPases signal transduction, subsequently leading to the assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007).|||Cell membrane|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP11A and an accessory beta subunit TMEM30A.|||Early endosome|||Endoplasmic reticulum membrane|||Membrane|||Proteolytically cleaved by CASP3.|||Recycling endosome|||Widely expressed. Expressed in myoblasts (PubMed:29799007). Expressed in retina, brain, liver, testes and kidney (at protein level) (PubMed:30018401). http://togogenome.org/gene/10090:Cd3d ^@ http://purl.uniprot.org/uniprot/P04235|||http://purl.uniprot.org/uniprot/Q3U4T1|||http://purl.uniprot.org/uniprot/Q3V3B4|||http://purl.uniprot.org/uniprot/Q6P5P1 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Membrane|||Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition of this role of signal transduction in T-cell activation, CD3D plays an essential role in thymocyte differentiation. Indeed, participates in correct intracellular TCR-CD3 complex assembly and surface expression. In absence of a functional TCR-CD3 complex, thymocytes are unable to differentiate properly (PubMed:10935641). Interacts with CD4 and CD8 and thus serves to establish a functional link between the TCR and coreceptors CD4 and CD8, which is needed for activation and positive selection of CD4 or CD8 T-cells.|||Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.|||The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with coreceptors CD4 and CD8.|||Thymocyte development in mice lacking CD3D is arrested at the double-positive stage with markedly diminished TCR expression. Thymocytes are defective in the induction of ERK pathway upon TCR engagement, whereas activation of other MAP kinases is unaffected. http://togogenome.org/gene/10090:Kif17 ^@ http://purl.uniprot.org/uniprot/A2AM72|||http://purl.uniprot.org/uniprot/Q99PW8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Dendrite-specific motor protein which, in association with the Apba1-containing complex (LIN-10-LIN-2-LIN-7 complex), transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules.|||Expressed from embryonic day 16, and expression increases to postnatal week 3.|||Highly expressed in the gray matter of the brain, especially in the hippocampus.|||Homodimer (PubMed:10846156). Interacts with APBA1 (via PDZ domain); the interaction is direct and is required for association of KIF17 with the cargo that is to be transported (PubMed:10846156). Interacts with IFT B complex components IFT52 and IFT57 (PubMed:23810713). Interacts with IFT70B (PubMed:23810713). Interacts with PIWIL1 (PubMed:16787948). Interacts with TBATA (PubMed:17196196).|||cilium|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Sim1 ^@ http://purl.uniprot.org/uniprot/Q61045 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in lung, skeletal muscle and kidney. During fetal development it is found in the CNS, developing kidney, mesodermal and endodermal tissues, including developing somites, mesonephric duct, and foregut.|||Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer; forms a heterodimer with ARNT, ARNT2.|||Nucleus|||Transcriptional factor that may have pleiotropic effects during embryogenesis and in the adult. http://togogenome.org/gene/10090:Lynx1 ^@ http://purl.uniprot.org/uniprot/P0DP60 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts in different tissues through interaction to nicotinic acetylcholine receptors (nAChRs) (PubMed:10402197). The proposed role as modulator of nAChR activity seems to be dependent on the nAChR subtype and stoichiometry, and to involve an effect on nAChR trafficking and its cell surface expression, and on single channel properties of the nAChR inserted in the plasma membrane.Modulates functional properties of nicotinic acetylcholine receptors (nAChRs) to prevent excessive excitation, and hence neurodegeneration. Enhances desensitization by increasing both the rate and extent of desensitization of alpha-4:beta-2-containing nAChRs and slowing recovery from desensitization. Promotes large amplitude ACh-evoked currents through alpha-4:beta-2 nAChRs (PubMed:10402197, PubMed:11906696). Is involved in regulation of the nAChR pentameric assembly in the endoplasmic reticulum. Shifts stoichiometry from high sensitivity alpha-4(2):beta-2(3) to low sensitivity alpha-4(3):beta-2(2) nAChR (PubMed:25193667). In vitro modulates alpha-3:beta-4-containing nAChRs. Reduces cell surface expression of (alpha-3:beta-4)(2):beta-4 and (alpha-3:beta-4)(2):alpha-5 nAChRs suggesting an interaction with nAChR alpha-3(-):(+)beta-4 subunit interfaces and an allosteric mode. Corresponding single channel effects characterized by decreased unitary conductance, altered burst proportions and enhanced desensitization/inactivation seem to depend on nAChR alpha:alpha subunit interfaces and are greater in (alpha-3:beta-2)(2):alpha-3 when compared to (alpha-3:beta-2)(2):alpha-5 nAChRs (By similarity). Prevents plasticity in the primary visual cortex late in life (PubMed:21071629).|||Cell membrane|||Endoplasmic reticulum|||Expressed at very low levels at birth and undergoes a marked up-regulation between postnatal days 10 and 20 (PubMed:10402197). Up-regulated in the visual cortex between postnatal day 28 (P28) and P60, when experience-dependent brain plasticity declines (PubMed:21071629).|||Expressed in neurons of multiple regions in the CNS, including the cerebral cortex, thalamus, substantia nigra, cerebellum, amygdala and hippocampus (PubMed:10402197, PubMed:11906696). Also expressed in kidney, heart and thymus, but at lower levels than in the brain (PubMed:10402197). Expressed in the primary visual cortex (V1) and the lateral geniculate nucleus (at protein level) (PubMed:21071629).|||Interacts with nAChRs containing alpha-4:beta-2 (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits (PubMed:11906696). Interacts with CHRNA4 probably in the endoplasmic reticulum prior to nAChR pentameric assembly (PubMed:19468303).|||Mutant mice show no gross abnormalities in size, viability, CNS morphology or longevity, but demonstrate enhanced performance in learning ability and memory and are more responsive to nicotine. Aging mutant mice exhibit a vacuolating neurodegeneration that is exacerbated by nicotine.|||dendrite http://togogenome.org/gene/10090:Cfap97 ^@ http://purl.uniprot.org/uniprot/Q6ZPR1 ^@ Similarity|||Tissue Specificity ^@ Belongs to the CFAP97 family.|||Highly expressed in testis with lower levels detected in other tissues including lung, heart and kidney. http://togogenome.org/gene/10090:Trim62 ^@ http://purl.uniprot.org/uniprot/Q80V85 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays a role in antifungal immunity by mediating 'Lys-27'-linked ubiquitination of CARD9 downstream of C-type lectin receptors; leading to CARD9 activation, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). E3 ubiquitin ligase activity is dependent on E2 ubiquitin-conjugating enzyme UBE2D2 (By similarity).|||Increased susceptibility to fungal infection.|||Interacts with the ubiquitin-conjugating enzyme, UBE2D2.|||Polyubiquitinated, autoubiquitinated in the presence of UBE2D2.|||The RING finger is required for ubiquitin ligase activity. http://togogenome.org/gene/10090:Mtmr10 ^@ http://purl.uniprot.org/uniprot/Q7TPM9 ^@ Caution|||Sequence Caution|||Similarity ^@ Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 399 in the dsPTPase catalytic loop, suggesting that it has no phosphatase activity.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Sequence of unknown origin in the N-terminal part. http://togogenome.org/gene/10090:Dhrs13 ^@ http://purl.uniprot.org/uniprot/Q5SS80 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Putative oxidoreductase.|||Secreted http://togogenome.org/gene/10090:Or5b99 ^@ http://purl.uniprot.org/uniprot/Q8VFX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vwc2 ^@ http://purl.uniprot.org/uniprot/Q8C8N3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, predominantly expressed in the developing diencephalon. At 16.5 dpc and 18.5 dpc, expressed in the brain, spinal cord, developing neural tubes and tongue but not in the cerebral cortex. At 16.5 dpc, present in developing oral and tooth germ epithelia (at protein level).|||BMP antagonist which may play a role in neural development. Promotes cell adhesion.|||Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including VWC2. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.|||Predominantly expressed in the brain (at protein level). It is expressed in the neurons but not the glial cells.|||Synapse|||basement membrane http://togogenome.org/gene/10090:Apoe ^@ http://purl.uniprot.org/uniprot/P08226|||http://purl.uniprot.org/uniprot/Q3TXU4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma. The extent of glycosylation and sialylation are tissue and context specific.|||APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (By similarity). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:23676495).|||APOE knockout mice display severe hypercholesterolemia associated with impaired clearance of dietary fats (PubMed:1423598). Excess cholesterol is more particularly associated with the atherogenic very low and intermediate density lipoproteins in the plasma (PubMed:1423598). These mice are therefore prone to atherosclerosis (PubMed:1423598). Mice lacking both Cx3cr1 and Apoe show decreased atherogenesis (PubMed:12569158). Animals with a double knockout of APOE and CD36, fed a Western diet for 12 weeks, exhibit much lower levels of CXCL1, CXCL2 and CCL5 mRNA expression in the descending aorta and a corresponding decrease in atherosclerotic lesion formation, compared to APOE single knockout mice (PubMed:23812099). Animals with a double knockout of APOE and TLR4 or TLR6 also have less aortic plaque formation than single knockout mice. All 3 double knockout show lower serum concentrations of IL1A, ILB and IL18 (PubMed:20037584). The melanosomes of APOE knockout mice lack the ellipsoidal shape indicative of deficient PMEL amyloidogenesis.|||Belongs to the apolipoprotein A1/A4/E family.|||Extracellular vesicle|||Glycated in plasma VLDL.|||Homotetramer. May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs. May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear. May interact with MAPT. May interact with MAP2. In the cerebrospinal fluid, interacts with secreted SORL1. Interacts with PMEL; this allows the loading of PMEL luminal fragment on ILVs to induce fibril nucleation.|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted|||extracellular matrix|||extracellular space|||multivesicular body http://togogenome.org/gene/10090:Pcp2 ^@ http://purl.uniprot.org/uniprot/P12660 ^@ Function|||Tissue Specificity ^@ Cerebellum (Purkinje cells) and retinal bipolar neurons.|||May function as a cell-type specific modulator for G protein-mediated cell signaling. http://togogenome.org/gene/10090:Creb3l1 ^@ http://purl.uniprot.org/uniprot/Q9Z125 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. ATF subfamily.|||Endoplasmic reticulum membrane|||Expressed in cortical and trabecular bones. Highly expressed in osteoblasts, but not detected in osteoclasts, nor in macrophages (PubMed:19767743). Expressed at relatively low levels in lung and kidney. Weakly expressed in brain and spleen. Expressed in astrocytes (PubMed:37178686).|||In the embryo, primarily expressed in the cartilage, tooth germs and salivary gland. Expressed in the inner enamel epithelium during the cap and bell stages (14.5 dpc - 18.5 dpc), in the preodontoblasts during differentiation stage (18.5 dpc - P0) and in the differentiating odontoblasts during the early secretory stage (P2.5-P4.5). After birth, at P14, detected at low levels in the cerebral cortex, hippocampus and thalamus. In the adult brain, expression becomes weaker.|||Interacts with SMAD4, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in assembly of collagen extracellular matrix.|||Mutant mice are born at the expected Mendelian rate, but show growth retardation. They exhibit severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts. Osteoblasts show abnormally expanded rough endoplasmic reticulum, containing of a large amount of bone matrix proteins, including COL1A1 and osteocalcin/BGLAP.|||N-glycosylated.|||Nucleus|||Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress or DNA damage, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus where it activates transcription of specific target genes involved in the cell-cycle progression inhibition.|||Transcription factor involved in cell type specific DNA damage and unfolded protein response (UPR) (PubMed:19767743, PubMed:37178686). Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (By similarity). Plays a critical role in bone formation through the transcription of COL1A1, and possibly COL1A2, and the secretion of bone matrix proteins. Directly binds to the UPR element (UPRE)-like sequence in an osteoblast-specific COL1A1 promoter region and induces its transcription. Does not regulate COL1A1 in other tissues, such as skin (PubMed:19767743). Required to protect astrocytes from ER stress-induced cell death. In astrocytes, binds to the cAMP response element (CRE) of the BiP/HSPA5 promoter and participate in its transcriptional activation (PubMed:15665855, PubMed:12480185). In astrocytes and osteoblasts, upon DNA damage, inhibits cell-cycle progression after G2/M phase by binding to promoters and activating transcription of genes encoding cell-cycle inhibitors, such as p21/CDKN1A (PubMed:37178686). Required for TGFB1 to activate genes involved in the assembly of collagen extracellular matrix (By similarity).|||Ubiquitinated by HRD1/SYVN1; undergoes 'Lys-48'-linked ubiquitination, followed by rapid proteasomal degradation under normal conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase dissociates from its substrate, ubiquitination does not occur and CREB3L1 is stabilized.|||Up-regulated in astrocytes residing in or close to CNS lesions, such as cryo-injured cerebral cortex and stab-injured spinal cord (PubMed:12480185, PubMed:15665855). Up-regulated by ER stress in astrocytes (at protein level). This induction is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain (PubMed:15665855). Induced in astrocytes upon DNA damage (PubMed:37178686). Up-regulated by BMP2 and RUNX2 in calvaria osteoblasts. This induction at the transcript and protein levels is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain, possibly through mild ER stress (PubMed:19767743). Also induced by BMP2 in bone marrow stromal cells.|||Upon ER stress or DNA damage, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain (PubMed:19767743, PubMed:37178686). The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2). RIP is induced by TGFB1 and ceramide. http://togogenome.org/gene/10090:Ssxb6 ^@ http://purl.uniprot.org/uniprot/A2BI74|||http://purl.uniprot.org/uniprot/Q6XAS1 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Ccdc28b ^@ http://purl.uniprot.org/uniprot/Q8CEG5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the retina, pericardium and limb epithelium.|||Interacts with BBS1, BBS2, BBS4, BBS5, BBS6, BBS7 and TTC8/BBS8. Interacts with MAPKAP1/SIN1 isoform 1 and RICTOR (By similarity).|||Involved in ciliogenesis. Regulates cilia length through its interaction with MAPKAP1/SIN1 but independently of mTORC2 complex. Modulates mTORC2 complex assembly and function, possibly enhances AKT1 phosphorylation. Does not seem to modulate assembly and function of mTORC1 complex.|||centrosome http://togogenome.org/gene/10090:Mlph ^@ http://purl.uniprot.org/uniprot/Q91V27 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds RAB27A that has been activated by GTP-binding via its N-terminus. Binds MYO5A via its C-terminal coiled coil domain.|||Highly expressed in embryos at day 7; not detectable at day 11. Highly expressed in adult stomach; detected at lower levels in kidney, lung, skin and small intestine. Detected in melanocytes.|||Melanosome|||Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A. http://togogenome.org/gene/10090:Clp1 ^@ http://purl.uniprot.org/uniprot/Q99LI9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Clp1 family. Clp1 subfamily.|||Component of the tRNA splicing endonuclease complex, composed of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54. Component of pre-mRNA cleavage complex II (CF-II). Also associates with numerous components of the pre-mRNA cleavage complex I (CF-I/CFIm), including NUDT21, CPSF2, CPSF3, CPSF6 and CPSF7. Interacts with CSTF2 and SYMPK.|||Early embryonic lethality.|||Nucleus|||Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double-stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Plays a key role in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex: phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA (PubMed:23474986, PubMed:24766809). Its role in tRNA splicing and maturation is required for cerebellar development (PubMed:24766809). Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing. http://togogenome.org/gene/10090:Mdfic2 ^@ http://purl.uniprot.org/uniprot/B2RVL9 ^@ Similarity ^@ Belongs to the MDFI family. http://togogenome.org/gene/10090:Tdrd5 ^@ http://purl.uniprot.org/uniprot/J3QPB7|||http://purl.uniprot.org/uniprot/Q5VCS6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TDRD5 family.|||Cytoplasm|||Gonad-specific. Mainly expressed in testis. Present at low level in ovary (at protein level).|||Male sterility because of spermiogenic arrest at the round spermatid stage, with occasional failure in meiotic prophase. Effects are due to demethylation and subsequent derepression of transposable elements: germ cells fail to repress LINE-1 (L1) retrotransposons with DNA-demethylated promoters. Defects in chromatoid body (CB) and pi-body assembly are also observed. Interestingly, Tdrd5-deficient round spermatids injected into oocytes contribute to fertile offspring, showing that acquisition of a functional haploid genome may be uncoupled from Tdrd5 function.|||Required during spermiogenesis to participate in the repression transposable elements and prevent their mobilization, which is essential for the germline integrity. Probably acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Required for chromatoid body (CB) assembly.|||Specifically expressed in germ cells of the developing testis, starting from 12.5 dpc. The protein is detected as early as 13.5 dpc in embryonic testes, but expression declines around the perinatal period and then is restored at around 2 weeks after birth. Also detected in the embryonic ovary at a low level. In adult testis, mainly present in the spermatocytes from the pachytene stage onward (at protein level). http://togogenome.org/gene/10090:Panx2 ^@ http://purl.uniprot.org/uniprot/Q6IMP4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pannexin family.|||Cell membrane|||Forms PANX1/PANX2-heteromeric intercellular channels on coexpression in paired Xenopus oocytes. Does not form homomeric channels (By similarity).|||Structural component of the gap junctions and the hemichannels.|||gap junction http://togogenome.org/gene/10090:Phospho2 ^@ http://purl.uniprot.org/uniprot/Q9D9M5 ^@ Function|||Similarity ^@ Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.|||Phosphatase that has high activity toward pyridoxal 5'-phosphate (PLP). Also active at much lower level toward pyrophosphate, phosphoethanolamine (PEA), phosphocholine (PCho), phospho-l-tyrosine, fructose-6-phosphate, p-nitrophenyl phosphate, and h-glycerophosphate. http://togogenome.org/gene/10090:Aff1 ^@ http://purl.uniprot.org/uniprot/A3KMF4|||http://purl.uniprot.org/uniprot/E9Q921 ^@ Similarity ^@ Belongs to the AF4 family. http://togogenome.org/gene/10090:Tm9sf2 ^@ http://purl.uniprot.org/uniprot/P58021|||http://purl.uniprot.org/uniprot/Q542E4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.|||Endosome membrane|||Golgi outpost|||In the intracellular compartments, may function as a channel or small molecule transporter.|||Membrane|||microtubule organizing center http://togogenome.org/gene/10090:Mpp4 ^@ http://purl.uniprot.org/uniprot/D3Z0G8|||http://purl.uniprot.org/uniprot/Q6P7F1 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAGUK family.|||Cytoplasm|||Detected in the retina (at protein level). Highly enriched in the retina where it is mainly expressed by rod photoreceptors; detected in the inner segment of the photoreceptor layer and in the outer nuclear layer. Also detected at much lower levels in pineal gland, cerebellum, cortex, hippocampus, olfactory bulb, heart, liver and spleen. Expressed in the CA1-CA3 regions of pyramidal cell layers and in the granule cell layer of dentate gyrus in the hippocampus. In the cerebellum, expressed in Purkinje cells and throughout the granule cell layer. In the olfactory bulb, expressed in mitral cells.|||Expressed postnatally in the retina. The expression in the retina coincides with one of the photoreceptor specific genes. Expressed in forebrain of 9.5 dpc embryos and in whole brain of 11.5 dpc embryos.|||Frameshifts and sequencing errors.|||May interact with GRIA2 (By similarity). Interacts with MPDZ. Forms a complex with CRB1 and PALS1. Interacts with FASLG (By similarity).|||May play a role in retinal photoreceptors development. http://togogenome.org/gene/10090:Erbb3 ^@ http://purl.uniprot.org/uniprot/Q61526 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.|||In the muscle, expression localizes to the synaptic sites of muscle fibers.|||Membrane|||Monomer and homodimer. Heterodimer with each of the other ERBB receptors (Potential). Interacts with CSPG5, PA2G4, GRB7 and MUC1 (By similarity). Interacts with MYOC (PubMed:23897819). Found in a ternary complex with NRG1 and ITGAV:ITGB3 or ITGA6:ITGB4 (By similarity).|||The cytoplasmic part of the receptor may interact with the SH2 or SH3 domains of many signal-transducing proteins.|||Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase. May also be activated by CSPG5. Involved in the regulation of myeloid cell differentiation. http://togogenome.org/gene/10090:Letmd1 ^@ http://purl.uniprot.org/uniprot/Q924L1 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in brown adipose tissue (BAT) (PubMed:34669999, PubMed:34910916, PubMed:36334589). Also detected at low levels in white adipose tissue (PubMed:34910916).|||Homozygous mice for Letmd1 gene are born at normal Mendelian ratios, with normal morphology, bodyweight and body composition at 2-months old (PubMed:34669999). Mice could not tolerate cold exposure without food (PubMed:34669999). Mutants exhibit impaired thermogenesis and are prone to diet-induced obesity and defective glucose disposal (PubMed:34910916).|||Interacts with BRI3BP. Interacts (via C-terminal) with SMARCA4; the interaction regulates transcriptional expression of thermogenic genes in brown adipose tissue (PubMed:34910916).|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Nucleus|||Plays an essential role for mitochondrial structure and function, as well as thermogenesis of brown adipocytes (PubMed:34669999, PubMed:34910916, PubMed:36334589). In brown adipose tissue also localizes in the nucleus where it interacts with the chromatin remodeler SMARCA4 to regulate thermogenic genes expression, such as UCP1 (PubMed:34910916). May regulate phagocytosis and inflammatory responses to lipopolysaccharide in macrophages (By similarity). Involved in tumorigenesis and may function as a negative regulator of the p53/TP53 (PubMed:12879013).|||Up-regulated in white and brown adipose tissues upon cold exposure and beta-adrenergic signaling. http://togogenome.org/gene/10090:Rbm20 ^@ http://purl.uniprot.org/uniprot/Q3UQS8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with components of the U1 and U2 U1 small nuclear ribonucleoprotein complexes.|||Cytoplasmic ribonucleoprotein granule|||During early embryonic cardiogenesis.|||Mice were born in normal Mendelian ratios, are viable, and do not exhibit any visible phenotype (PubMed:29650543). They however develop cardiomyopathy and display splicing defects in genes related to calcium handling such as CAMK2D or RYR2 (PubMed:29650543).|||Nucleus|||Phosphorylation regulates the subcellular localization. Phosphorylation of Ser-637 and Ser-639 in the RS (arginine/serine-rich) region promotes nuclear localization of the protein (PubMed:29895960, PubMed:35394688). In contrast, phosphorylation of the C-terminal disordered region promotes localization to cytoplasmic ribonucleoprotein granules (By similarity).|||Predominantly expressed in striated muscle, with highest expression in the heart (PubMed:22466703, PubMed:23886709). In differentiating myoblasts, expression correlates with sarcomere assembly: expression peaks when alpha-actinin is localized mainly in mature Z bodies within the nascent myofiber and expression declines as the sarcomeres continue to mature (PubMed:22466703). Also expressed in kidney (PubMed:23886709).|||RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH (PubMed:22466703, PubMed:24584570, PubMed:27630136, PubMed:29650543, PubMed:29895960, PubMed:33110103, PubMed:35394688, PubMed:35041844). Acts as a repressor of mRNA splicing: specifically binds the 5'UCUU-3' motif that is predominantly found within intronic sequences of pre-mRNAs, leading to the exclusion of specific exons in target transcripts (PubMed:32187365). RBM20-mediated exon skipping is hormone-dependent and is essential for TTN isoform transition in both cardiac and skeletal muscles (PubMed:27630136, PubMed:29895960, PubMed:33110103, PubMed:35041844). RBM20-mediated exon skipping of TTN provides substrates for the formation of circular RNA (circRNAs) from the TTN transcripts (PubMed:37272356). Together with RBM24, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes (By similarity). http://togogenome.org/gene/10090:Eif2b5 ^@ http://purl.uniprot.org/uniprot/Q8CHW4 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the eIF-2B gamma/epsilon subunits family.|||Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.|||Complex of five different subunits; alpha, beta, gamma, delta and epsilon. Interacts with RGS2 (By similarity).|||Phosphorylated at Ser-540 by DYRK2; this is required for subsequent phosphorylation by GSK3B. Phosphorylated on serine and threonine residues by GSK3B; phosphorylation inhibits its function (By similarity).|||Polyubiquitinated, probably by NEDD4. http://togogenome.org/gene/10090:Dbil5 ^@ http://purl.uniprot.org/uniprot/O09035 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ACBP family.|||Cytoplasm|||Exclusively expressed in late spermatids and spermatozoa. Not found in epididymis, spleen, bone marrow, skin, liver, brain, heart, kidney, muscle.|||Expression is seen first at day 45 of post-natal development (post-meiotic transcription).|||May be involved in the energy metabolism of the mature sperm. http://togogenome.org/gene/10090:Pcdhga12 ^@ http://purl.uniprot.org/uniprot/Q91XY7 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Tbc1d23 ^@ http://purl.uniprot.org/uniprot/Q8K0F1 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle|||Directly interacts with GOLGA1 and GOLGA4 (PubMed:29084197). Interacts with FAM91A1, C17ORF75 and WDR11; the interaction recruits TBC1D23 to AP-1-derived vesicles (PubMed:29084197). Directly interacts with WASHC1 and WASHC2/FAM21 (PubMed:29084197). Interacts with FKBP15 (PubMed:29084197).|||Mutant mice exhibit increased inflammatory cytokine production and recruit more inflammatory cells to the peritoneum, when challenged with different pathogen-associated molecular patterns (PAMPs), including LPS.|||Putative Rab GTPase-activating protein which plays a role in vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (PubMed:29084197). Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1 (By similarity). Plays a role in brain development, including in cortical neuron positioning. May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes which are essential for axonal and dendritic growth (PubMed:28823707). May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge (PubMed:22312129).|||trans-Golgi network http://togogenome.org/gene/10090:Nxf3 ^@ http://purl.uniprot.org/uniprot/Q4ZGD9 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Rax ^@ http://purl.uniprot.org/uniprot/O35602 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Expressed in the photoreceptor and inner nuclear layers.|||Nucleus|||Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation. Binds to the photoreceptor conserved element-I (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter (By similarity).|||Strongly expressed in anterior neural plate at 8.5 dpc, followed in optic sulci and ventral forebrain at 9.0 dpc, and in eye at 10.5 dpc uniformly expressed in neuroretina at 15.5 dpc, and at later stages, expression decreases. http://togogenome.org/gene/10090:She ^@ http://purl.uniprot.org/uniprot/Q8BSD5 ^@ Tissue Specificity ^@ Expressed in heart, brain, lung and skeletal muscle. http://togogenome.org/gene/10090:Syt7 ^@ http://purl.uniprot.org/uniprot/Q9R0N7 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per C2 domain.|||Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain. Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis. SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (PubMed:26738595). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (By similarity). Ca(2+)-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (PubMed:16982801, PubMed:21041449). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (PubMed:18539119). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes (PubMed:25860611). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (PubMed:24569478, PubMed:26738595). Probably mediates synaptic facilitation by directly increasing the probability of release (PubMed:26738595). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (PubMed:24569478). Also acts as a regulator of Ca(2+)-dependent insulin and glucagon secretion in beta-cells (PubMed:18308938, PubMed:19171650). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (PubMed:20956309). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity).|||Cell membrane|||Homodimer (PubMed:10871604). Can also form heterodimers with SYT6, SYT9 and SYT10 (PubMed:10871604). Interacts with calmodulin (CALM1, CALM2 or CALM3) (PubMed:24569478). Interacts with CD63; required for localization to lysosomes (PubMed:21041449). Interacts with APP (PubMed:30429473).|||Lysosome membrane|||Major isoform.|||No visible phenotype. Mice were born at the expected Mendelian ratio and do not show gross abnormalities and/or obvious neurological defects. Mice have a normal life span and are fertile, although reproductive capacity is declining faster with age (PubMed:12925704). Embryonic fibroblasts from Syt7 deficient mice are less susceptible to Trypanosoma cruzi invasion, and display impaired lysosomal exocytosis and resealing after wounding (PubMed:12925704). Mutant mice display impaired insulin secretion: they exhibit normal insulin sensitivity and normal metabolic and Ca(2+) responses but impaired insulin release, due to Ca(2+)-sensing defects (PubMed:18308938). Impaired glucagon secretion (PubMed:19171650). Neurons show enhanced synaptic depression: spontaneous synaptic vesicle release is unaffected, while replenishment is impaired (PubMed:24569478). Abolished synaptic facilitation at all synapses except for mossy fiber synapses, where the remaining enhancement is consistent with use-dependent spike broadening that occurs at this synapse (PubMed:26738595). The loss of facilitation is not due to slowed recovery from depression. The initial probability of release and the presynaptic residual Ca(2+) signals are not affected (PubMed:26738595).|||Palmitoylated at its vesicular N-terminus; palmitoylation is required for localization to lysosome and phagocytosis in macrophages.|||Peroxisome membrane|||Presynaptic cell membrane|||The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins. The two C2 domains bind independently to planar membranes, without interdomain cooperativity. Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins.|||Widely expressed. Expressed in insulin-secreting cells (PubMed:18308938). Present in glucagon-secreting cells (at protein level) (PubMed:19171650).|||phagosome membrane|||secretory vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:H13 ^@ http://purl.uniprot.org/uniprot/Q9D8V0 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase A22B family.|||Catalyzes intramembrane proteolysis of some signal peptides after they have been cleaved from a preprotein, resulting in the release of the fragment from the ER membrane into the cytoplasm. Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides. Involved in the intramembrane cleavage of the integral membrane protein PSEN1. Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner (By similarity). May play a role in graft rejection (PubMed:9354467).|||Cell membrane|||Endoplasmic reticulum membrane|||In the embryo, expression starts at day 6.5.|||Membrane|||Monomer. Homodimer (By similarity). Interacts with RNF139 (PubMed:19720873). Interacts with DERL1 and XBP1 isoform 1 (By similarity).|||The first transmembrane domain may act as a type I signal anchor. The PAL motif is required for normal active site conformation.|||Widely expressed with highest levels in liver and kidney. In the brain, expressed predominantly in hippocampus, amygdala, piriform cortex, choroid plexus and arcuate nucleus of the hypothalamic area. Isoform 1 is more strongly expressed than isoform 4 in most tissues except brain and skeletal muscle where isoform 4 is the dominant isoform and in testis where isoform 1 and isoform 4 are expressed at similar levels. In the brain, isoform 4 is not detected in the choroid plexus. http://togogenome.org/gene/10090:Lctl ^@ http://purl.uniprot.org/uniprot/Q8K1F9 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the glycosyl hydrolase 1 family, Asp-200 is present instead of the conserved Glu which is an active site residue. It is therefore expected that this protein lacks glycosidase activity.|||Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.|||Endoplasmic reticulum membrane|||May form dimers.|||No visible phenotype. The lens of the eye appears normal in young animals. However, formation of the lens suture is abnormal with an X-shaped or double-Y shaped morphology instead of a tight Y-shaped pattern. Optics of the lens are distorted and cortical cataracts develop; the phenotype progressively worsens with age. Expression of CLIC5 in the lens epithelium is almost completely absent.|||Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens.|||Strongly expressed in the lens of the eye, where it localizes to the equatorial epithelium and outer layers of newly extending fiber cells (at protein level) (PubMed:29425878). May also be expressed in kidney and skin (PubMed:12084582). However, another study suggests that expression is specific to eye and is minimal in other tissues (PubMed:29425878). http://togogenome.org/gene/10090:Or10a4 ^@ http://purl.uniprot.org/uniprot/Q7TRM9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrps5 ^@ http://purl.uniprot.org/uniprot/Q99N87 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS5 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Spag17 ^@ http://purl.uniprot.org/uniprot/Q5S003 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the central pair apparatus of ciliary axonemes. Plays a critical role in the function and structure of motile cilia (PubMed:23418344, PubMed:15827353). May play a role in endochondral bone formation, most likely because of a function in primary cilia of chondrocytes and osteoblasts (PubMed:26017218). Essential for normal spermatogenesis and male fertility (PubMed:29690537). Required for normal manchette structure, transport of proteins along the manchette microtubules and formation of the sperm head and flagellum (PubMed:29690537). Essential for sperm flagellum development and proper assembly of the respiratory motile cilia central pair apparatus, but not the brain ependymal cilia (PubMed:32988999).|||Cytoplasm|||Defects in Spag17 are the cause of primary ciliary dyskinesia only (Pcdo) phenotype. Mice are generally viable to adulthood but have a significantly shortened lifespan, with chronic morbidity. Show neonatal progressive hydrocephalus, accumulation of mucus in the respiratory passages and male infertility.|||Deficient mice die within 12 hours of birth with severe defects in motile cilia (PubMed:23418344). Mice also have skeletal malformations (PubMed:26017218). Male mice are infertile because of a severe defect in spermatogenesis (PubMed:29690537). Spermatids display abnormally long manchette structures and defects in the morphology of the sperm head, acrosome, and tail (PubMed:29690537). Additionally, the transport of proteins along the manchette microtubules is disrupted in the elongating spermatids (PubMed:29690537).|||Expressed from day 16 when pachytene spermatocytes are present.|||Golgi apparatus|||Highly expressed in testis, round spermatids, testicular sperm, epididymal sperm and in condensing spermatids (at protein level) (PubMed:15827353, PubMed:29690537, PubMed:32988999). Expressed in organs that contain cilia-bearing cells including brain, oviduct, lung, and uterus (PubMed:15827353, PubMed:32988999). Expressed in articular cartilage and bone (PubMed:26017218).|||Interacts (via the C-terminus) with SPAG6; the interaction probably occurs on polymerized microtubules.|||Missing sequence in a highly repetitive region between exons 21 and 22.|||acrosome|||cytoskeleton|||flagellum axoneme http://togogenome.org/gene/10090:Park7 ^@ http://purl.uniprot.org/uniprot/Q99LX0 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C56 family.|||By hydrogen peroxide.|||Cell membrane|||Cytoplasm|||Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.|||Endoplasmic reticulum|||Expressed in erythroblasts and in mature red blood cells from peripheral blood (at protein level) (PubMed:20800516). In pancreas, expression is higher in islets than surrounding exocrine tissues (PubMed:22611253).|||Expression increases during erythroid development (at protein level) (PubMed:20800516). In pancreatic islets, expression increases during aging (PubMed:22611253).|||Glyoxalase activity has been reported (PubMed:22523093). It may however reflect its deglycase activity.|||Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Binds to HIPK1 (By similarity). Interacts (via N-terminus) with OTUD7B (PubMed:21097510). Interacts with BBS1, CLCF1 and MTERF (PubMed:21097510). Interacts (via C-terminus) with NCF1; the interaction is enhanced by LPS and modulates NCF1 phosphorylation and membrane translocation (PubMed:26021615). Interacts with NENF (PubMed:31536960).|||Increased sensitivity of embryonic cortical neurons to oxidative stress. Age-dependent increase in mitochondrial hydrogen peroxide production and reduced mitochondrial aconitase activity. Down-regulation of Slc25a14 and Slc25a27, compromised calcium-induced uncoupling and increased oxidation of mitochondrial matrix proteins specifically in the dopaminergic neurons of the substantia nigra pars compacta. Reduced N2el2 protein expression. Impaired mitochondrial function and morphology with reduced autophagy leading to accumulation of defective mitochondria. Targeted knockouts in astrocytes exhibit augmented LPS-induced CRK/p38 phosphorylation and signaling, they don't stimulate TLR4 endocytosis upon LPS stimulation. Knockout animals present increased bacterial burdens, reduced local and systemic inflammation, macrophage paralysis and impaired induction of pro-inflammatory cytokines, such as IL6 and TNF, under the condition of sepsis (PubMed:26021615). Mutants from 12 weeks old, but not younger, show higher levels of reactive oxygen species (ROS) and mitochondrial fragmentation in pancreatic islets. They have lower levels of plasma insulin after glucose challenge, display glucose intolerance and have reduced beta-cell area. Younger mutants kept on a high fat diet also show lower levels of plasma insulin, display glucose intolerance and have reduced beta-cell area (PubMed:22611253). Animals become diabetic upon multiple low doses of streptozotocin with reduced insulin concentrations, higher fasting blood glucose concentrations and higher rates of beta cell apoptosis compared to wild type (PubMed:26422139).|||Membrane raft|||Mitochondrion|||Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease (PubMed:15784737, PubMed:17015834, PubMed:20800516, PubMed:21068725). It is involved in neuroprotective mechanisms like the stabilization of NFE2L2 and PINK1 proteins, male fertility as a positive regulator of androgen signaling pathway as well as cell growth and transformation through, for instance, the modulation of NF-kappa-B signaling pathway (PubMed:17015834, PubMed:21097510). Has been described as a protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. But this function is rebuted by other works. As a protein deglycase, repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage. Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair. Protects histones from adduction by methylglyoxal, controls the levels of methylglyoxal-derived argininine modifications on chromatin. Able to remove the glycations and restore histone 3, histone glycation disrupts both local and global chromatin architecture by altering histone-DNA interactions as well as histone acetylation and ubiquitination levels. Displays a very low glyoxalase activity that may reflect its deglycase activity (PubMed:22523093). Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death (PubMed:17766438). Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria (PubMed:20186336). Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking (PubMed:21068725). Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells (PubMed:23847046, PubMed:19276172). In pancreatic islets, involved in the maintenance of mitochondrial reactive oxygen species (ROS) levels and glucose homeostasis in an age- and diet dependent manner. Protects pancreatic beta cells from cell death induced by inflammatory and cytotoxic setting (PubMed:26422139). Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress (By similarity). Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (PubMed:23792957). In macrophages, interacts with the NADPH oxidase subunit NCF1 to direct NADPH oxidase-dependent ROS production, and protects against sepsis (PubMed:26021615).|||Nucleus|||Sumoylated on Lys-130 by PIAS2 or PIAS4; which is essential for cell-growth promoting activity and transforming activity.|||The protein deglycation activity is controversial. It has been ascribed to a TRIS buffer artifact by a publication and as a result of the removal of methylglyoxal by glyoxalase activity that leads to a subsequent decomposition of hemithioacetals and hemianimals due to the shift in equilibrium position by another one. However, biochemical experiments showing that PARK7 is a bona fide deglycase have been performed.|||Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress. http://togogenome.org/gene/10090:Galnt1 ^@ http://purl.uniprot.org/uniprot/O08912 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor (PubMed:9153242, PubMed:10037781). Has a broad spectrum of substrates such as apomucin-, MUC5AC-, MUC1- and MUC2-derived peptides (By similarity).|||Golgi stack membrane|||Secreted|||The ricin B-type lectin domain directs the glycopeptide specificity. It is required in the glycopeptide specificity of enzyme activity but not for activity with naked peptide substrates, suggesting that it triggers the catalytic domain to act on GalNAc-glycopeptide substrates (By similarity).|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.|||Widely expressed at high level. Higher expression in kidney, heart, small intestine and cervix and to a lesser extent in all the other tissues tested. http://togogenome.org/gene/10090:Syt15 ^@ http://purl.uniprot.org/uniprot/Q8C6N3 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Detected from 7 dpc.|||Homodimer.|||Isoform 1 and isoform 2 are expressed in heart, lung, skeletal muscle and testis; not detected in brain, liver and kidney. Isoform 1 is expressed in spleen.|||May be due to intron retention.|||May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues.|||Membrane|||Neither C2 domains mediates Ca(2+)-dependent or Ca(2+)-independent phospholipid binding. http://togogenome.org/gene/10090:Arhgap45 ^@ http://purl.uniprot.org/uniprot/Q3TBD2 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity.|||Cytoplasm|||Rho-GAP domain is able to regulate RhoGTPase activity, actin cytoskeleton and cell spreading. However N-terminally BAR domain plays an autoinhibitory role.|||ruffle membrane http://togogenome.org/gene/10090:Znfx1 ^@ http://purl.uniprot.org/uniprot/Q8R151 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZNFX1 family.|||By interferons (IFNs) (PubMed:31685995). Expression is induced upon viral infection (PubMed:31685995).|||Interacts with MAVS.|||Mice are viable without obvious physiological or behavioral abnormalities (PubMed:31685995). They however display impaired innate immune responses against RNA virus infection by producing less type I interferons (IFNs) (PubMed:31685995).|||Mitochondrion outer membrane|||RNA-binding protein that initiates the antiviral response and is required to restrict the replication of RNA viruses (PubMed:31685995). Acts as a double-stranded RNA (dsRNA) sensor that recognizes viral RNA and then interacts with MAVS to initiate the type I interferon response (PubMed:31685995). Also required for immunity against some bacteria, such as mycobacteria (By similarity).|||Stress granule http://togogenome.org/gene/10090:Cdr2l ^@ http://purl.uniprot.org/uniprot/A2A6T1 ^@ Similarity ^@ Belongs to the CDR2 family. http://togogenome.org/gene/10090:Bcl2l11 ^@ http://purl.uniprot.org/uniprot/O54918|||http://purl.uniprot.org/uniprot/Q542N5 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Bcl-2 family.|||By ER stress.|||Expressed in a number of B- and T-lymphoid cell lines.|||Forms heterodimers with a number of antiapoptotic Bcl-2 proteins including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1.|||Forms heterodimers with a number of antiapoptotic Bcl-2 proteins, including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1, and BCL2L2/BCLW (PubMed:16543145, PubMed:27013495, PubMed:14499110). Interacts with BAX (in vitro); this interaction may induce the conformationally active form of BAX (PubMed:14499110). Does not heterodimerize with proapoptotic proteins such as BAD, BOK or BAK. Identified in a complex containing BCL2L11, DYNLL1 and BCL2L1 isoform Bcl-X(L); BH3 integrity is required for BCL2L1-binding (PubMed:21478148, PubMed:27013495, PubMed:14499110). Interacts with YWHAZ. When phosphorylated, interacts with TRIM2; this interaction is associated with ubiquitination and degradation (PubMed:21478148). Interacts (via BH3) with MCL1; this interaction may sequester BCL2L11 and prevent its pro-apoptotic activity (PubMed:16543145, PubMed:27013495). When phosphorylated, isoform BimEL interacts with USP27X; this interaction leads to BCL2L11 deubiquitination and stabilization (PubMed:27013495). Interacts with GIMAP5 (PubMed:16509771). Interacts with BCL2L10/BCL-B (By similarity).|||Induces apoptosis and anoikis.|||Induces apoptosis and anoikis. The isoforms vary in cytotoxicity with isoform BimS being the most potent and isoform BimEL being the least potent.|||Membrane|||Mitochondrion|||Phosphorylation at Ser-65 by MAPK1/MAPK3 leads interaction with TRIM2 and ubiquitination, followed by proteasomal degradation (PubMed:21478148). Deubiquitination catalyzed by USP27X stabilizes the protein (PubMed:27013495).|||The BH3 motif is required for the interaction with Bcl-2 proteins and cytotoxicity.|||Ubiquitination by TRIM2 following phosphorylation by MAPK1/MAPK3 leads to proteasomal degradation. Conversely, deubiquitination catalyzed by USP27X stabilizes the protein. http://togogenome.org/gene/10090:Spata25 ^@ http://purl.uniprot.org/uniprot/Q9DA57 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SPATA25 family.|||Expressed strongly in testis, weakly in epididymis and not detected in other tissues.|||Expression is detected at day 15 after birth and gradually increases from day 15 to 5 months. Expression is found in round spermatids with little expression in spermatogonia.|||May play a role in spermatogenesis.|||Membrane http://togogenome.org/gene/10090:Ppfia2 ^@ http://purl.uniprot.org/uniprot/B8QI34|||http://purl.uniprot.org/uniprot/F7CYX4|||http://purl.uniprot.org/uniprot/Q8BSS9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alters PTPRF cellular localization and induces PTPRF clustering. May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. In neuronal cells, is a scaffolding protein in the dendritic spines which acts as immobile postsynaptic post able to recruit KIF1A-driven dense core vesicles to dendritic spines.|||Belongs to the liprin family. Liprin-alpha subfamily.|||Cell surface|||Cytoplasm|||Forms homodimers and heterodimers with liprins-alpha and liprins-beta. Interacts with the second PTPase domain of PTPRD, PTPRF and PTPRS. Interacts with KIF1A; the interaction decreases in presence of calcium.|||The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type alpha/alpha. The C-terminal, non-coiled coil regions mediate heterodimerization type alpha/beta and interaction with PTPRD, PTPRF and PTPRS (By similarity).|||dendritic spine http://togogenome.org/gene/10090:Pm20d2 ^@ http://purl.uniprot.org/uniprot/A3KG59 ^@ Function|||Similarity ^@ Belongs to the peptidase M20A family.|||Catalyzes the peptide bond hydrolysis in dipeptides having basic amino acids lysine, ornithine or arginine at C-terminus. Postulated to function in a metabolite repair mechanism by eliminating alternate dipeptide by-products formed during carnosine synthesis. http://togogenome.org/gene/10090:Lhpp ^@ http://purl.uniprot.org/uniprot/Q9D7I5 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAD-like hydrolase superfamily.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Homodimer.|||Nucleus|||Phosphatase that hydrolyzes imidodiphosphate, 3-phosphohistidine and 6-phospholysine. Has broad substrate specificity and can also hydrolyze inorganic diphosphate, but with lower efficiency (By similarity). http://togogenome.org/gene/10090:Hoxa5 ^@ http://purl.uniprot.org/uniprot/P09021 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Antp homeobox family.|||Expressed during embryogenesis and in adult kidney.|||Forms a DNA-binding heterodimer with transcription factor PBX1.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Also binds to its own promoter. Binds specifically to the motif 5'-CYYNATTA[TG]Y-3'. http://togogenome.org/gene/10090:Meiob ^@ http://purl.uniprot.org/uniprot/Q9D513 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MEIOB family.|||Chromosome|||Component of a multiprotein complex with RPA2 and SPATA22. Interacts with the complex BRME1:HSF2BP:BRCA2 (PubMed:32345962).|||Cytoplasm|||Detected only during early meiosis prophase I (early 4N-fraction containing leptotene, zygotene and few pachytenes spermatocytes) and not during later stages of meiosis (at protein level).|||Mice develop and grow normally but show infertility in both sexes. Infertility is due to a meiotic arrest at a zygotene/pachytene-like stage. DNA double strand break repair and homologous chromosome synapsis are impaired in meiocytes.|||Nucleus|||Single-stranded DNA-binding protein required for homologous recombination in meiosis I. Required for double strand breaks (DSBs) repair and crossover formation and promotion of faithful and complete synapsis. Not required for the initial loading of recombinases but required to maintain a proper number of RAD51 and DMC1 foci after the zygotene stage. May act by ensuring the stabilization of recombinases, which is required for successful homology search and meiotic recombination. Displays Single-stranded DNA 3'-5' exonuclease activity in vitro.|||Sprecifically expressed in early meiotic germ cells: in adult and fetal tissues, detected in fetal ovary, postnatal testis and liver. In the ovary, expression starts at 12.5 dpc, reaches a maximum at 15.5 dpc and decreases to become undetectable in post natal life. In testis, expression starts at 10 days post partum (dpp), reaches a maximum at 20 dpp and is maintained throughout adult life. http://togogenome.org/gene/10090:Pdpn ^@ http://purl.uniprot.org/uniprot/Q62011 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||At 12.5 dpc and 13.5 dpc is expressed in the endothelial cells of forming lymph sacs.|||Basolateral cell membrane|||Belongs to the podoplanin family.|||Detected at high levels in lung and brain, at lower levels in kidney, stomach, liver, spleen and esophagus, and not detected in skin and small intestine. Expressed in epithelial cells of choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells and in endothelia of lymphatic vessels. Also expressed in stromal cells of peripheral lymphoid tissue and thymic epithelial cells. Detected in carcinoma cell lines and cultured fibroblasts. Expressed at higher levels in colon carcinomas than in normal colon tissue.|||Down-regulated by treatment with puromycin aminonucleoside (PubMed:12032185). Up-regulated during progression to highly aggressive tumors and during epithelial-mesenchymal transition (EMT) (PubMed:20962267).|||Extensively O-glycosylated. Contains sialic acid residues. O-glycosylation is necessary for platelet aggregation activity. Disialylated at Thr-52; sialic acid is critical for platelet-aggregating activity and for CLEC1B interaction (By similarity).|||Homodimer. Interacts with CLEC1B; the interaction is independent of CLEC1B glycosylation and activates CLEC1B; the interaction is dependent of sialic acid on O-glycans (PubMed:17616532). Interacts with CD9; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Interacts with LGALS8; the interaction is glycosylation-dependent; may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix. Interacts with HSPA9. Interacts (via extracellular domain) with CD44; this interaction is required for PDPN-mediated directional migration and regulation of lamellipodia extension/stabilization during cell spreading and migration. Interacts (via cytoplasmic domain) with MSN and EZR; activates RHOA and promotes epithelial-mesenchymal transition. Interacts with CCL21; relocalized PDPN to the basolateral membrane (By similarity).|||Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation (PubMed:14522983, PubMed:15231832, PubMed:20110424, PubMed:17616532). Interaction with CD9, on the contrary, attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Mediates effects on cell migration and adhesion through its different partners. Through MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness. Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (By similarity). In lymph nodes (LNs), controls fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR; MSN and RDX) and MYL9 activation through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation (PubMed:25347465). Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix (By similarity). In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion (PubMed:10574709). Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1 (By similarity). Required for normal lung cell proliferation and alveolus formation at birth (PubMed:12654292). Does not function as a water channel or as a regulator of aquaporin-type water channels (By similarity). Does not have any effect on folic acid or amino acid transport (PubMed:12032185).|||Membrane|||Membrane raft|||Mice die at birth of respiratory failure due to a low number of attenuated type I cells, narrow and irregular air spaces, and defective formation of alveolar saccules (PubMed:12654292). Knockout Pdpn mice neonates are smaller, and approximately 55% died during the first postnatal week. However, approximately 20% survived, had normal weights and life spans, and are fertile (PubMed:20110424).|||Phosphorylated by PKA; decreases cell migration.|||The N-terminus is blocked.|||The cytoplasmic domain controls FRC elongation but is dispensable for contraction (PubMed:25347465). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (By similarity).|||filopodium membrane|||invadopodium|||lamellipodium membrane|||microvillus membrane|||ruffle membrane http://togogenome.org/gene/10090:Iqcb1 ^@ http://purl.uniprot.org/uniprot/Q8BP00 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with calmodulin (PubMed:15723066). Interacts with CEP290/NPHP6; IQCB1/NPHP5 and CEP290/NPHP6; are proposed to form a functional NPHP5-6 module localized to the centrosome. Interacts with ATXN10. Interacts with NPHP1, INVS, NPHP4 and RPGRIP1L; these interactions likely require additional interactors (PubMed:21565611). Associates with the BBSome complex; interacts with BBS1, BBS2, BBS4, BBS5, BBS7, BBS8 and BBS9 (By similarity).|||Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6 (By similarity). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2 and BBS5 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating CEP290/NPHP6 (By similarity).|||Localized to the outer segment and connecting cilia of photoreceptor cells.|||The IQ domains mediate the interaction with calmodulin.|||centrosome http://togogenome.org/gene/10090:Vmn2r80 ^@ http://purl.uniprot.org/uniprot/E9Q1L0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Trmt6 ^@ http://purl.uniprot.org/uniprot/Q8CE96 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRM6/GCD10 family.|||Heterotetramer; composed of two copies of TRMT6 and two copies of TRMT61A.|||Nucleus|||Substrate-binding subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA. Together with the TRMT61A catalytic subunit, part of a mRNA N(1)-methyltransferase complex that mediates methylation of adenosine residues at the N(1) position of a small subset of mRNAs: N(1) methylation takes place in tRNA T-loop-like structures of mRNAs and is only present at low stoichiometries. http://togogenome.org/gene/10090:M1ap ^@ http://purl.uniprot.org/uniprot/Q9Z0E1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in germ cells of the testis. Expressed from spermatogonia to spermatids. Expressed at very low levels in lung, stomach, thymus. Not detected in Sertoli cells.|||Germ cell-specific, but may also be expressed in cells that require the presence of germ cells. Cranial to caudal punctate expression is seen in the developing ovary starting at 13.5 dpc. At 13.5 dpc. expressed in the cranial part of the XX gonad. At 14.5 dpc, expression extends to almost two-thirds of the XX gonad, and by 15.5 dpc expression is seen throughout the entire organ. By 16.5 dpc, expression is only detected in the most caudal tip of the XX gonad. Expression switches from the embryonic ovary to the postnatal testis.|||Males show reduced testicular size and a tubular defects, which led to severe oligozoospermia and infertility. Spermatocytes are eliminated via apoptosis either at the pachytene checkpoint, or later at the spindle checkpoint during metaphase I.|||Required for meiosis I progression during spermatogenesis.|||Seems to synergize with Cbfb and Myh11 during the onset of acute myeloid leukemia. http://togogenome.org/gene/10090:Gng8 ^@ http://purl.uniprot.org/uniprot/P63078|||http://purl.uniprot.org/uniprot/Q3UMY0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||G proteins are composed of 3 units; alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. This subunit may have a very specific role in the development and turnover of olfactory and vomeronasal neurons.|||Membrane http://togogenome.org/gene/10090:Arx ^@ http://purl.uniprot.org/uniprot/O35085 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Expressed in the developing forebrain and also in the floor plate (PubMed:9256348). Expressed in the interstitium of the male gonad at 14.5 dpc, but only weakly in a region of the female gonad proximal to the mesonephros (PubMed:12379852).|||Hemizygous knockout males were born at 19.5 dpc and died within a half day (PubMed:12379852). Neonatal males have small brains, small olfactory bulbs, small testes, hypoplasia of the seminal vesicle and abnormally enlarged seminiferous tubules (PubMed:12379852). Abnormal morphology in each of the developing brain regions in which ARX is normally expressed (PubMed:12379852). Suppressed proliferation and nearly normal migration of neuroepithelial cells in the neocortex (PubMed:12379852). Aberrant formation of many nerve fiber tracts at 19.5 dpc (PubMed:12379852). Abnormal primary migration of GABAergic interneurons from the ganglionic eminence (PubMed:12379852). Abolished expression of wingless-related WNT8B and LIM homeobox protein LHX9 in the thalamic eminence at 12.5 dpc, and decreased expression of DLX1 in the ventral thalamus at 12.5 dpc (PubMed:12379852). Testes have a dysplastic interstitium, probably owing to a considerable decrease in cells containing an abundant cytoplasm as the interstitium is occupied predominantly by fibroblast-like cells (PubMed:12379852). Expression of Leydig cell marker HSD3B1 is severely diminished in the interstitial region of testes, suggesting that Leydig cell differentiation is blocked (PubMed:12379852). Expression of KDM5C is reduced at both mRNA and protein levels (PubMed:31691806). Increased expression of SYN1, SCN2A and some isoforms of BDNF (PubMed:31691806).|||Nucleus|||Transcription factor (By similarity). Binds to specific sequence motif 5'-TAATTA-3' in regulatory elements of target genes, such as histone demethylase KDM5C (By similarity). Positively modulates transcription of KDM5C (PubMed:31691806). Activates expression of KDM5C synergistically with histone lysine demethylase PHF8 and perhaps in competition with transcription regulator ZNF711; synergy may be related to enrichment of histone H3K4me3 in regulatory elements (By similarity). Required for normal brain development (PubMed:12379852). Plays a role in neuronal proliferation, interneuronal migration and differentiation in the embryonic forebrain (PubMed:12379852, PubMed:31691806). May also be involved in axonal guidance in the floor plate (PubMed:9256348). http://togogenome.org/gene/10090:Htra4 ^@ http://purl.uniprot.org/uniprot/A2RT60 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1C family.|||Secreted|||Serine protease. http://togogenome.org/gene/10090:Meiosin ^@ http://purl.uniprot.org/uniprot/A0A5K7RLP0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Gatekeeper of meiotic initiation in both male and female germ cells (PubMed:32032549). In complex with STRA8, directly activates the transcription of a subset of critical meiotic genes playing a central role in cell-cycle switching from mitosis to meiosis. Temporal expression of MEIOSIN is required for meiotic entry decision (PubMed:32032549).|||Induced in 13.5 dpc in the embryonic ovary, expression persists at least until 18.5 dpc (PubMed:32032549). In testes, expressed in spermatocytes during the preleptotene stage in the stage VII-VIII seminiferous tubules (at protein level) (PubMed:32032549).|||Interacts with STRA8.|||Mutant mice develop normally. Males show defects in reproductive organs with smaller-than-normal testes (PubMed:32032549). They have severely impaired spermatogenesis and the absence of postmeiotic spermatids or sperm in testes and epididymis (PubMed:32032549). Female ovaries are degenerated with apparently fewer mature follicles at the age of 4 weeks old (PubMed:32032549).|||Nucleus|||Specifically expressed in adult testis and embryonic ovary. http://togogenome.org/gene/10090:Mfsd4b5 ^@ http://purl.uniprot.org/uniprot/E9PYY6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or2ag19 ^@ http://purl.uniprot.org/uniprot/Q9EPF5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Stab1 ^@ http://purl.uniprot.org/uniprot/G3X973 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Irf2 ^@ http://purl.uniprot.org/uniprot/P23906|||http://purl.uniprot.org/uniprot/Q3U2Z2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by CBP/ p300 during cell-growth. Acetylation on Lys-75 is required for stimulation of H4 promoter activity (By similarity).|||Belongs to the IRF family.|||By viruses and IFN.|||Interacts with BRD7, IRF2BP1 and IRF2BP2. Interacts with CREBBP in growing cells; the interaction acetylates IRF2 and regulates IRF2-dependent H4 promoter activity (By similarity).|||Nucleus|||Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) and represses those genes. Also acts as an activator for several genes including H4 and IL7. Constitutively binds to the ISRE promoter to activate IL7. Involved in cell cycle regulation through binding the site II (HiNF-M) promoter region of H4 and activating transcription during cell growth. Antagonizes IRF1 transcriptional activation.|||The major sites of sumoylation are Lys-137 and Lys-293. Sumoylation with SUMO1 increases its transcriptional repressor activity on IRF1 and diminishes its ability to activate ISRE and H4 promoter (By similarity). http://togogenome.org/gene/10090:Mfng ^@ http://purl.uniprot.org/uniprot/O09008|||http://purl.uniprot.org/uniprot/Q3UPI0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in inhibition of NOTCH1 activation by JAG1 and enhancement of NOTCH1 activation by DLL1 via an increase in its binding to DLL1.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Ift172 ^@ http://purl.uniprot.org/uniprot/Q6VH22 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT172 family.|||Co-localizes with RABL2/RABL2A in the midpiece of elongated spermatids within the testis (at protein level). Expressed in the flagellum of elongated spermatids and sperm in the testis lumen (at protein level) (PubMed:24339785).|||Interacts with IFT88 (PubMed:11062270). Interacts with IFT57 (PubMed:23810713). Interacts with RABL2/RABL2A; binds preferentially to GDP-bound RABL2 (PubMed:23055941).|||Intron retention. The sequence is a pre-RNA and intronic sequences remain.|||Required for the maintenance and formation of cilia. Plays an indirect role in hedgehog (Hh) signaling, cilia being required for all activity of the hedgehog pathway.|||cilium http://togogenome.org/gene/10090:Mefv ^@ http://purl.uniprot.org/uniprot/Q9JJ26 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals are grossly normal, with no obvious changes in thymus, spleen or lymph nodes. In vitro, resident peritoneal macrophage cells show enhanced IL1B and IL18 release in response to inflammatory stimuli.|||Cytoplasm|||Degraded along with the delivery of its substrates to autolysosomal compartments (at protein level).|||Expressed in spleen peripheral blood granulocytes. Not expressed in lymphocytes, thymus, testis, ovary, heart, brain, lung, liver, kidney and muscle.|||Homotrimer. Interacts (via the B box-type zinc finger) with PSTPIP1 (By similarity). Interacts (via the B30.2/SPRY domain) with several components of the inflammasome complex, including CASP1 p20 and p10 subunits, CASP5, PYCARD, NLRP1, NLRP2 and NLRP3, as well as with unprocessed IL1B; this interaction may lead to autophagic degradation of these proteins (By similarity). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287). Interacts with NFKBIA and RELA (By similarity). Interacts weakly with VASP and ACTR3 (By similarity). Interacts with active ULK1 (phosphorylated on 'Ser-317') and BECN1 simultaneously (By similarity). Also interacts with ATG16L1 (via WD repeats), and with ATG8 family members, including GABARAP, GABARAPL1 and, to a lesser extent, GABARAPL2, MAP1LC3A/LC3A and MAP1LC3C/LC3C (By similarity). Interacts with TRIM21 (By similarity). Interacts with TRIM21 (By similarity). Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; the interaction is required for the down-regulation of pyrin pro-inflammatory activity (By similarity).|||Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (PubMed:34471287). Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy (By similarity). Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity). However, it can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production (By similarity). Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (PubMed:34471287). It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation (By similarity). Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization (By similarity).|||Lacks the B30.2/SPRY domain found in the human ortholog, thus may have divergent function(s).|||Nucleus|||Phosphorylation at Ser-241 is required for the interaction with 14-3-3 proteins and down-regulation of pyrin pro-inflammatory activity.|||The B box-type zinc finger interacts, possibly intramolecularly, with the pyrin domain; this may be an autoinhibitory mechanism released by PSTPIP1 binding.|||autophagosome|||cytoskeleton|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Egfr ^@ http://purl.uniprot.org/uniprot/Q01279|||http://purl.uniprot.org/uniprot/Q9EP98 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.|||Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. Heterodimer with ERBB2. Forms a complex with CCDC88A/GIV (via SH2-like region) and GNAI3 which leads to enhanced EGFR signaling and triggering of cell migration; binding of CCDC88A requires autophosphorylation of the EGFR C-terminal region, and ligand stimulation is required for recruitment of GNAI3 to the complex (By similarity). Interacts with ERRFI1; inhibits dimerization of the kinase domain and autophosphorylation. Part of a complex with ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter protein coupling the receptor to downstream signaling pathways. Interacts with GAB2; involved in signaling downstream of EGFR. Interacts with STAT3; mediates EGFR downstream signaling in cell proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. Interacts (autophosphorylated) with CBL, CBLB and CBLC; involved in EGFR ubiquitination and regulation; interaction with CBL is reduced in the presence of tensin TNS4. Interacts with SOCS5; regulates EGFR degradation through ELOC- and ELOB-mediated ubiquitination and proteasomal degradation. Interacts with PRMT5; methylates EGFR and enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG1; essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with TNK2; this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. Interacts (via SH2 domains) with GRB2, NCK1 and NCK2. Interacts with EPS8; mediates EPS8 phosphorylation. Interacts with ATXN2. Interacts with GAREM1. Interacts (ubiquitinated) with ANKRD13A/B/D; the interaction is direct and may regulate EGFR internalization after EGF stimulation. Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts (via C-terminal cytoplasmic kinase domain) with ZPR1 (via zinc fingers). Interacts with RNF115 and RNF126. Interacts with GPRC5A (via its transmembrane domain) (PubMed:25744720). Interacts with FAM83B; positively regulates EGFR inducing its autophosphorylation in absence of stimulation by EGF (By similarity). Interacts with LAPTM4B; positively correlates with EGFR activation (By similarity). Interacts with STX19 (PubMed:16420529). Interacts with CD44 (By similarity). Interacts with PGRMC1; the interaction requires PGRMC1 homodimerization (By similarity). Interacts with PIKFYVE (PubMed:17909029). Interacts with NEU3. Interacts with TRAF4. Interacts with the ant venom OMEGA-myrmeciitoxin(02)-Mg1a (PubMed:35131940).|||Cell membrane|||Endocytosis and inhibition of the activated EGFR by phosphatases like PTPRJ and PTPRK constitute immediate regulatory mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR endocytosis and activity. Moreover, inducible feedback inhibitors including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative regulatory mechanisms for the EGFR signaling.|||Endoplasmic reticulum membrane|||Endosome|||Endosome membrane|||Golgi apparatus membrane|||Membrane|||Methylated. Methylation at Arg-1199 by PRMT5 stimulates phosphorylation at Tyr-1197.|||Mice are growth retarded and die at different stages of development depending on their genetic background. Embryonic death is due to placental defects. Mice surviving until birth or later display brain, bone, heart and various epithelial development defects in several organs, including skin, lung and gastrointestinal tract.|||Monoubiquitinated and polyubiquitinated upon EGF stimulation; which does not affect tyrosine kinase activity or signaling capacity but may play a role in lysosomal targeting. Polyubiquitin linkage is mainly through 'Lys-63', but linkage through 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitinated by OTUD7B, preventing degradation (By similarity). Ubiquitinated by RNF115 and RNF126. Ubiquitinated by ZNRF1 or CBL at different lysines in response to EGF stimulation; leading to recruitment of the ESCRT machinery and subsequent degradation in the lysosomes (By similarity). Deubiquitinated by UCHL1 leading to the inhibition of its degradation (PubMed:32494592).|||Nucleus|||Nucleus membrane|||Palmitoylated on Cys residues by ZDHHC20. Palmitoylation inhibits internalization after ligand binding, and increases the persistence of tyrosine-phosphorylated EGFR at the cell membrane. Palmitoylation increases the amplitude and duration of EGFR signaling.|||Phosphorylated on Tyr residues in response to EGF. Phosphorylation at Ser-697 is partial and occurs only if Thr-695 is phosphorylated. Phosphorylation at Thr-680 and Thr-695 by PRKD1 inhibits EGF-induced MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis and stabilizes the receptor at the plasma membrane. Autophosphorylation at Tyr-1199 is stimulated by methylation at Arg-1199 and enhances interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 recruits STAT3. Dephosphorylated by PTPN1 and PTPN2.|||Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:8404850). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (By similarity). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (By similarity). Plays a role in enhancing learning and memory performance (PubMed:20639532). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (PubMed:35131940). http://togogenome.org/gene/10090:Or5as1 ^@ http://purl.uniprot.org/uniprot/Q7TR55 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rassf2 ^@ http://purl.uniprot.org/uniprot/Q8BMS9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts directly with activated KRAS in a GTP-dependent manner. Interacts (via SARAH domain) with STK3/MST2 and STK4/MST1.|||Nucleus|||Phosphorylated by STK3/MST2 and STK4/MST1.|||Potential tumor suppressor. Acts as a KRAS-specific effector protein. May promote apoptosis and cell cycle arrest. Stabilizes STK3/MST2 by protecting it from proteasomal degradation (By similarity).|||kinetochore http://togogenome.org/gene/10090:Cthrc1 ^@ http://purl.uniprot.org/uniprot/Q9D1D6 ^@ Function|||PTM|||Subcellular Location Annotation ^@ May act as a negative regulator of collagen matrix deposition.|||N-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Brd2 ^@ http://purl.uniprot.org/uniprot/Q7JJ13 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly (By similarity). May play a role in spermatogenesis or folliculogenesis.|||Homodimer. Interacts with E2F1 and with histone H4 acetylated at 'Lys-13' (By similarity).|||Nucleus|||One bromodomain is sufficient for a partial interaction with histone H4 acetylated at 'Lys-13'.|||Predominantly expressed in the testis, followed by ovary, placenta, embryo and to a lower extent in somatic tissues. http://togogenome.org/gene/10090:Art4 ^@ http://purl.uniprot.org/uniprot/Q9CRA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the Arg-specific ADP-ribosyltransferase family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prkar2a ^@ http://purl.uniprot.org/uniprot/Q8K1M3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cAMP-dependent kinase regulatory chain family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Oxr1 ^@ http://purl.uniprot.org/uniprot/E9Q0A7|||http://purl.uniprot.org/uniprot/Q4KMM3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the OXR1 family.|||Highly expressed in brain and testis.|||May be involved in protection from oxidative damage.|||Mitochondrion|||nucleolus http://togogenome.org/gene/10090:Ttc36 ^@ http://purl.uniprot.org/uniprot/Q8VBW8 ^@ Similarity ^@ Belongs to the TTC36 family. http://togogenome.org/gene/10090:Vapb ^@ http://purl.uniprot.org/uniprot/Q8BH80 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Ugt1a2 ^@ http://purl.uniprot.org/uniprot/P70691 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||Endoplasmic reticulum membrane|||Expressed in kidney.|||Microsome|||UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. http://togogenome.org/gene/10090:Zfp740 ^@ http://purl.uniprot.org/uniprot/Q6NZQ6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Psmb7 ^@ http://purl.uniprot.org/uniprot/P70195 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase T1B family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.|||Cytoplasm|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.|||Up-regulated by the antioxidant dithiolethione (D3T) in colon (at protein level). http://togogenome.org/gene/10090:Tmem265 ^@ http://purl.uniprot.org/uniprot/E9Q8G3 ^@ Similarity ^@ Belongs to the CD225/Dispanin family. http://togogenome.org/gene/10090:Ss18l1 ^@ http://purl.uniprot.org/uniprot/Q8BW22 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SS18 family.|||Homodimer. Dimerization may be necessary for its function in neuronal dendritic development. Interacts (via C-terminus) with CREBBP (via N-terminus), EP300 and SMARCA4/BRG1. Interacts with the nBAF complex. Association with CREBBP facilitates transcription while the association with SMARCA4/BRG1 suppresses CREST-mediated transcription in resting neurons (By similarity).|||Mice are smaller than littermates and show coordination defects. There is increased mortality in beginning at about P14, and about 80% die by P28. Less than 20% survive to adulthood, and they are infertile.|||Nucleus|||The MFD (multi-functional domain) domain is involved in transcription transactivation, nuclear body targeting and dimerization.|||Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP.|||kinetochore http://togogenome.org/gene/10090:Naca ^@ http://purl.uniprot.org/uniprot/P70670|||http://purl.uniprot.org/uniprot/Q60817 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NAC-alpha family.|||Cardiac- and muscle-specific transcription factor. May act to regulate the expression of genes involved in the development of myotubes. Plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. Involved in the organized assembly of thick and thin filaments of myofibril sarcomeres.|||Cytoplasm|||Expressed concomitant with the onset of mineralization in ossification centers of developing bone.|||Induced in muscle by wounding.|||Interacts (via PXLXP motif) with the muscle-restricted histone methyltransferase SMYD1 (via MYND-type zinc finger).|||Isoform 1 appears to be ubiquitously expressed.|||Nucleus|||Part of the nascent polypeptide-associated complex (NAC), which is a heterodimer of NACA and BTF3 (via NAC-A/B domains). NAC associates with ribosomes through the BTF3/NACB subunit and contacts the ribosomal protein L23, which is positioned near the exiting site. Both subunits can contact nascent polypeptide chains. NACA may also form homodimers, and only this form binds DNA (By similarity). Interacts with TBP and JUN.|||Partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation. Viable skNAC(-/-) adult mice have reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells have impaired survival compared with wild-type.|||Phosphorylation of Ser-2015 by ILK during cell adhesion may promote nuclear localization. Phosphorylation of Thr-2131 by GSK3B may promote proteasome mediated degradation.|||Phosphorylation of Ser-43 by ILK during cell adhesion may promote nuclear localization. Phosphorylation of Thr-159 by GSK3B may promote proteasome mediated degradation.|||Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites) (By similarity). Isoform 1 and isoform 2 appear to bind DNA and play roles in transcription. Isoform 1 may function as a specific coactivator for JUN, acting to stabilize the interaction of JUN homodimers with promoter elements.|||Specifically expressed in heart and skeletal muscle: it is present in differentiated myotubes but not in myoblasts.|||The positively charged inner surface of the NAC-A/B domain is crucial for NACA localization in the nucleus and DNA-binding. This region is blocked from binding nucleic acids in the heterodimeric complex by a helix region in the beta-subunit, it also displays much higher affinity for RNA than DNA (By similarity). http://togogenome.org/gene/10090:Cd33 ^@ http://purl.uniprot.org/uniprot/Q63994 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||CD33-deficient mice are viable and fertile in a pathogen-free environment without any obvious deficiency in overall organ development and growth.|||Cell membrane|||Expressed on myeloid precursors in the bone marrow. In the peripheral blood, mostly expressed on granulocytes.|||Glycosylated.|||Homodimer; disulfide-linked. Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation. Interacts with C1QA (via C-terminus); this interaction activates CD33 inhibitory motifs.|||Phosphorylation is involved in binding to PTPN6 and PTPN11.|||Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state (By similarity). Preferentially binds sialic acid to the short O-linked glycans of certain mucins (PubMed:12773563). http://togogenome.org/gene/10090:Slco2b1 ^@ http://purl.uniprot.org/uniprot/Q3TQJ3|||http://purl.uniprot.org/uniprot/Q3V1K7|||http://purl.uniprot.org/uniprot/Q8BXB6 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A conserved histidine residue in the third transmembrane domain (His-128) might play an essential role in the pH sensitivity of SLCO2B1/OATP2B1-mediated substrate transport. Transmembrane domain 1 (TM1) may be localized within the substrate binding pocket.|||Apical cell membrane|||Basal cell membrane|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Expressed in liver, kidney, small intestine mucosa, large intestine, brain, lung, spleen, stomach and heart.|||Knockout mice show no difference in growth rate, viability, fertility, progeny, life span, weight, organs, tissues and serum biochemistry (PubMed:31123035). Knockout females exhibit an increased in Cyp2c65 and Cyp2c66 gene expression, but not males (PubMed:32114507). Knockout mice exhibit a decreased plasma concentration of certain drugs administered orally such as fexofenadine and fluvastatin, whereas no difference were observed after intravenous administration (PubMed:31123035, PubMed:32114507). Also exhibit a decreased in the hepatic uptake of drugs erlotinib and mebrofenin after intravenous injection (PubMed:34205780). Don't show any difference in fluvastatin liver concentration after oral injection (PubMed:32114507).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the Na(+)-independent transport of steroid sulfate conjugates such as estrone 3-sulfate (E1S), dehydroepiandrosterone sulfate (DHEA-S) and pregnenolone sulfate (PregS) and other specific organic anions (PubMed:31123035). Responsible for the transport of E1S through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including DHEA-S (By similarity). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver. Mediates the intestinal uptake of sulfated steroids. Mediates the uptake of the neurosteroids DHEA-S and PregS into the endothelial cells of the blood-brain barrier as the first step to enter the brain. Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons. May act as a heme transporter that promotes cellular iron availability. Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (By similarity). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:31123035). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment. The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound. Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions. Cytoplasmic glutamate may also act as counteranion in the placenta. An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (By similarity).|||Membrane|||Most likely contributes to the absorption and the disposition of a wide range of drugs in the intestine and the liver. http://togogenome.org/gene/10090:Vstm2b ^@ http://purl.uniprot.org/uniprot/Q9JME9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Gm14632 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Uqcrfs1 ^@ http://purl.uniprot.org/uniprot/Q9CR68 ^@ Caution|||Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Rieske iron-sulfur protein family.|||Binds 1 [2Fe-2S] cluster per subunit. Fe-S cluster delivery to the Rieske protein is mediated by components of the iron sulfur (Fe-S) cluster assembly machinery that reside in the mitochondrial matrix (including HSC20 and LYRM7) (By similarity).|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783). Incorporation of the Rieske protein UQCRFS1 is the penultimate step in complex III assembly (By similarity). Interacts with TTC19, which is involved in the clearance of UQCRFS1 fragments (PubMed:28673544).|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII). Subunit 9 corresponds to the mitochondrial targeting sequence (MTS) of Rieske protein UQCRFS1. It is retained after processing and incorporated inside complex III, where it remains bound to the complex and localizes between the 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII). UQCRFS1 undergoes proteolytic processing once it is incorporated in the complex III dimer. One of the fragments, called subunit 9, corresponds to its mitochondrial targeting sequence (MTS). The proteolytic processing is necessary for the correct insertion of UQCRFS1 in the complex III dimer, but the persistence of UQCRFS1-derived fragments may prevent newly imported UQCRFS1 to be processed and assembled into complex III and is detrimental for the complex III structure and function.|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. The Rieske protein is a catalytic core subunit containing a [2Fe-2S] iron-sulfur cluster. It cycles between 2 conformational states during catalysis to transfer electrons from the quinol bound in the Q(0) site in cytochrome b to cytochrome c1 (By similarity). Incorporation of UQCRFS1 is the penultimate step in complex III assembly (By similarity).|||Mitochondrion inner membrane|||Proteolytic processing is necessary for the correct insertion of UQCRFS1 in the complex III dimer. Several fragments are generated during UQCRFS1 insertion, most probably due to the endogenous matrix-processing peptidase (MPP) activity of the 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, which are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively. The action of the protease is also necessary for the clearance of the UQCRFS1 fragments.|||Several peptides are generated during UQCRFS1 insertion (PubMed:28673544). According to some authors, the identification of the transit peptide as the subunit 9, does not necessary imply that it must be considered as a structural subunit of the complex III dimer as additional fragments from UQCRFS1 are also present (PubMed:28673544).|||The Rieske protein is a high potential 2Fe-2S protein. http://togogenome.org/gene/10090:Rbm17 ^@ http://purl.uniprot.org/uniprot/Q8JZX4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds SXL. Associates with the spliceosome. Interacts with SF3B1, SF1 and U2AF2 (By similarity).|||Nucleus|||Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites (By similarity). http://togogenome.org/gene/10090:Zwint ^@ http://purl.uniprot.org/uniprot/Q9CQU5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with ZW10 and MIS12. Interacts with the NDC80 subunit of the NDC80 complex specifically during mitosis. Also interacts with KNL1, CETN3, DSN1 and PMF1 (By similarity).|||Nucleus|||Part of the MIS12 complex, which is required for kinetochore formation and spindle checkpoint activity. Required to target ZW10 to the kinetochore at prometaphase (By similarity).|||kinetochore http://togogenome.org/gene/10090:Or5p64 ^@ http://purl.uniprot.org/uniprot/Q8VG02 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Topbp1 ^@ http://purl.uniprot.org/uniprot/Q6ZQF0 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Deubiquitinated by USP13; leading to TOPBP1 stabilizion and activation of the ATR-TOPBP1 axis pathway.|||Highly expressed in testis.|||Interacts with POLE. Interacts with RAD9A. Interacts with UBR5. Interacts with E2F1. Interacts with PML. Interacts with SMARCA2. Interacts with SMARCA4. Interacts with RHNO1. May interact with TOP2B. Interacts with TICRR. Interacts with HELB.|||Levels increase during the first 3 weeks after birth and remain high in the fourth week.|||Nucleus|||Phosphorylated on serine and threonine residues in response to X-ray irradiation.|||Required for DNA replication (By similarity). Plays a role in the rescue of stalled replication forks and checkpoint control (PubMed:14718568). Binds double-stranded DNA breaks and nicks as well as single-stranded DNA (By similarity). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters. Down-regulates E2F1 activity and inhibits E2F1-dependent apoptosis during G1/S transition and after DNA damage (By similarity). Induces a large increase in the kinase activity of ATR (By similarity).|||Ubiquitinated and degraded by the proteasome. X-ray irradiation reduces ubiquitination.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Arl8a ^@ http://purl.uniprot.org/uniprot/Q8VEH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||Interacts with PLEKHM1.|||Late endosome membrane|||Lysosome membrane|||Plays a role in lysosomes motility (PubMed:30174114). In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function (PubMed:30174114). May play a role in chromosome segregation (By similarity).|||Synapse|||axon|||spindle http://togogenome.org/gene/10090:Tnip1 ^@ http://purl.uniprot.org/uniprot/Q9WUU8 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Embryonic lethal. Mice develop an inflammatory disease with characteristics of human systemic lupus erythematosus (SLE), including the appearance of immature granulocytes in the peripheral blood and development of autoreactive antibodies and glomerulonephrititis.|||Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG (By similarity). Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases.|||Interacts with TNFAIP3 and IKBKG (polyubiquitinated); facilitates TNFAIP3-mediated de-ubiquitination of NEMO/IKBKG. Interacts with polyubiquitin. Interacts with MAPK1, SELPLG and PIK3CD. Interacts with IRAK1 (polyubiquitinated). Interacts with MYD88; the interaction is indicative for participation in an activated TLR-signaling complex. Interacts with TAX1BP1 (By similarity).|||Nucleus|||Phosphorylation at Tyr-565 by SRC-family kinases recruits phosphoinositide-3-kinase (PI3K) PIK3CD:p85 heterodimer which results in integrin activation and leukocyte adhesion to activated endothelium during inflammation.|||Ubiquitous. Abundant in heart and skeletal muscle and expressed at lower levels in thymus, liver, kidney, brain and intestinal tract. http://togogenome.org/gene/10090:Mucl3 ^@ http://purl.uniprot.org/uniprot/Q3TNW5 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Cytoplasm|||May modulate NF-kappaB signaling and play a role in cell growth. http://togogenome.org/gene/10090:Eprs ^@ http://purl.uniprot.org/uniprot/Q8CGC7 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Homodimer. Part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that is composed of the tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18. Forms a linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit complex (PubMed:12060739). Interacts with TARS3 (By similarity). Interacts with DUS2L (By similarity). Component of the GAIT complex which is composed of EPRS1, RPL13A and GAPDH (PubMed:23071094). Interacts (phosphorylated at Ser-999) with SLC27A1; mediates the translocation of SLC27A1 from the cytoplasm to the plasma membrane thereby increasing the uptake of long-chain fatty acids (PubMed:28178239).|||In the C-terminal section; belongs to the class-II aminoacyl-tRNA synthetase family.|||In the N-terminal section; belongs to the class-I aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 2 subfamily.|||Membrane|||Multifunctional protein which is primarily part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (By similarity). The phosphorylation of EPRS1, induced by interferon-gamma, dissociates the protein from the aminoacyl-tRNA synthetase multienzyme complex and recruits it to the GAIT complex that binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing their translation. Interferon-gamma can therefore redirect, in specific cells, the EPRS1 function from protein synthesis to translation inhibition (PubMed:23071094). Also functions as an effector of the mTORC1 signaling pathway by promoting, through SLC27A1, the uptake of long-chain fatty acid by adipocytes. Thereby, it also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239).|||Phosphorylated at Ser-999 by RPS6KB1; triggers EPRS1 release from the aminoacyl-tRNA synthetase multienzyme complex. In monocytes, the IFN-gamma-induced phosphorylation at Ser-999 releases EPRS1 from the aminoacyl-tRNA synthetase multienzyme complex, allowing its association with the GAIT complex. Phosphorylation at Ser-999 is specifically required for the RPL13A-mediated interaction of the GAIT complex with eIF4G (By similarity). Phosphorylation at Ser-999 by RPS6KB1, is also induced by insulin through activation of the mTORC1 signaling pathway and promotes the interaction of EPRS1 with SLC27A1 (PubMed:28178239).|||The WHEP-TRS domains are involved in RNA binding.|||cytosol http://togogenome.org/gene/10090:Or2ag18 ^@ http://purl.uniprot.org/uniprot/Q8VFM5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Serpinb6e ^@ http://purl.uniprot.org/uniprot/I7HJI3 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Or8b9 ^@ http://purl.uniprot.org/uniprot/Q8VF62 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cemip ^@ http://purl.uniprot.org/uniprot/Q8BI06 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activity is up-regulated by histamine.|||Belongs to the CEMIP family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||Expressed in Deiters' cells and various supporting cells in the organ of Corti including inner phalangeal, border, inner and outer pillar cells (at protein level). Weakly expressed in brain and testis. In ear, it is specifically expressed in inner ear. Expressed in Deiters' cells in the organ of Corti at P0 (postnatal day zero) before the onset of hearing, but disappears by day P7. Also expressed in fibrocytes of the spiral ligament and the spiral limbus through to P21, when the cochlea matures.|||Expressed throughout development.|||Interacts with EPHA2 and ITPR3. Interacts with HSPA5/BIP; the interaction induces calcium leakage from the endoplasmic reticulum and cell migration. Interacts with clathrin heavy chain/CLTC (By similarity).|||Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.|||N-glycosylated; glycosylation is not necessary for HA-binding.|||Nucleus|||Secreted|||The signal sequence is essential in mediating its proper translocation, hyaluronic acid (HA) degradation activity and secretion.|||clathrin-coated pit http://togogenome.org/gene/10090:Fam174a ^@ http://purl.uniprot.org/uniprot/Q9D3L0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM174 family.|||Membrane http://togogenome.org/gene/10090:Atp2b1 ^@ http://purl.uniprot.org/uniprot/G5E829 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.|||Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis (PubMed:22311909, PubMed:16956963, PubMed:28827723, PubMed:26392310, PubMed:29950683, PubMed:24805951, PubMed:23266958). Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction (PubMed:24805951, PubMed:29950683, PubMed:22311909). Positively regulates bone mineralization through absorption of calcium from the intestine (PubMed:23266958, PubMed:26392310). Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts (PubMed:23266958). Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells (By similarity). May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles.|||Cell membrane|||Complete embryonic lethality (PubMed:15178683). Mice with conditional knockout of ATP2B1 in enterocytes, are born at a lower frequency and are smaller at birth and into adulthood than wild-type. At two months of age, mice have a decreased bone mineral density (PubMed:26392310). Mice with conditional knockout of ATP2B1 in vascular smooth muscle cells (VSMCs) are born at the expected Mendelian ratio and grow normaly but have a higher blood pressure than wild-type under resting conditions (PubMed:22311909). Heterozygous ATP2B1 mice are hypertensive and exhibit hypocalcemia and a higher bone mineral density (PubMed:29950683).|||Expressed in the retina, with strongest expression in the outer plexiform layer and lower expression levels in the inner nuclear layer and the inner plexiform layer (PubMed:12209837). Specifically expressed in the following retinal cell types: photoreceptor cells, cone bipolar cells and horizontal cells (PubMed:12209837). Expressed in osteoclasts (at protein level) (PubMed:23266958). Expressed at highest levels in brain, intestine, kidney, and stomach, and at lower levels in liver, lung, aorta, portal vein, urinary bladder, diaphragm, seminal vesicles and testes (PubMed:15178683). Expressed in small intestinal epithelium (PubMed:23460639).|||Monomer. Dimer. Oligomer. Calmodulin binding. Interacts with PDZD11. Interacts with SLC35G1 and STIM1. Interacts with YWHAE; interacts with the monomeric and dimeric forms of the YWHAE but prefer the monomer form; this interaction inhibits calcium-transporting ATPase activity (By similarity). Interacts with NPTN; this interaction stabilizes ATP2B1 and increases ATPase activity; this interaction controls T cell calcium homeostasis following T cell activation (PubMed:28827723). Interacts with EPB41; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1 (PubMed:23460639).|||Presynaptic cell membrane|||Synapse|||Up-regulated following T cell activation.|||Up-regulated in differentiating osteoclasts.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Afg3l2 ^@ http://purl.uniprot.org/uniprot/Q8JZQ2 ^@ Cofactor|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent protease which is essential for axonal and neuron development (PubMed:18337413, PubMed:27642048). In neurons, mediates degradation of SMDT1/EMRE before its assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU (By similarity). Required for the maturation of paraplegin (SPG7) after its cleavage by mitochondrial-processing peptidase (MPP), converting it into a proteolytically active mature form. Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (By similarity). Involved in the regulation of OMA1-dependent processing of OPA1 (By similarity). Contributes to the proteolytic degradation of GHITM upon hyperpolarization of mitochondria (By similarity). Progressive GHITM degradation upon persistent hyperpolarization leads to respiratory complex I degradation and broad reshaping of the mitochondrial proteome by AFG3L2 (By similarity).|||Binds 1 zinc ion per subunit.|||Defects in Afg3l2 are the cause of the paralyze (par) phenotype, a spontaneous mutant strain. Par mice have a normal appearance and fertility but are significantly smaller than their littermates at 1 week of age and display a rapidly progressive loss of motor function in all limbs by 12-14 days. As the disease progresses, they lose the ability to support their own weight or turn themselves over when placed on their back and exhibit a typical posture with over extension of all limbs and uncoordinated movements. They rarely survive beyond 16 days of age, when they are completely paralyzed.|||Highly expressed in the cerebellar Purkinje cells.|||Homooligomer (PubMed:17101804). Forms heterooligomers with SPG7 and AFG3L1 (PubMed:17101804, PubMed:19656850). Interacts with SPG7; the interaction is required for the efficient assembly of mitochondrial complex I (PubMed:22563492, PubMed:19656850). Interacts with AFG3L1 (PubMed:19656850). Interacts with MAIP1 (PubMed:27642048). Interacts with DNAJC19 and PHB2 (PubMed:24856930). Interacts with GHITM (By similarity).|||In the C-terminal section; belongs to the peptidase M41 family.|||In the N-terminal section; belongs to the AAA ATPase family.|||Mitochondrion inner membrane|||Upon import into the mitochondrion, the N-terminal transit peptide is cleaved to generate an intermediate form which undergoes autocatalytic proteolytic processing to generate the proteolytically active mature form. http://togogenome.org/gene/10090:Or8i2 ^@ http://purl.uniprot.org/uniprot/A2AVB5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or8g37 ^@ http://purl.uniprot.org/uniprot/Q8VFN3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r95 ^@ http://purl.uniprot.org/uniprot/E9PUW9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cip2a ^@ http://purl.uniprot.org/uniprot/Q8BWY9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in 17.5 and 18.5 dpc liver but not expressed in adult liver. Expressed at moderate level in embryonic brain, muscle and epidermal layers.|||Homodimer. Interacts with MYC. Interacts with PPP2R5C; this interaction stabilizes CIP2A. Interacts with PPP2R1A; this interaction stabilizes CIP2A.|||Membrane|||Promotes anchorage-independent cell growth and tumor formation. http://togogenome.org/gene/10090:Slc35a2 ^@ http://purl.uniprot.org/uniprot/A2AER4|||http://purl.uniprot.org/uniprot/Q3UIP1|||http://purl.uniprot.org/uniprot/Q9JIH0|||http://purl.uniprot.org/uniprot/Q9R0M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.|||Golgi apparatus membrane|||Interacts with SLC35A3; the interaction is reduced in the presence of SLC35A4 (By similarity). Found in a complex with SLC35A3 and SLC35A4 (By similarity).|||Membrane|||Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus (PubMed:10578063). It functions as an antiporter that exchanges UDP-galactose for UMP (By similarity). It is also able to exchange UDP-galactose for AMP and CMP, and to transport UDP-N-acetylgalactosamine (UDP-GalNAc) and other nucleotide sugars (By similarity). As a provider of UDP-galactose to galactosyltransferases present in the Golgi apparatus, it is necessary for globotriaosylceramide/globoside (Gb3Cer) synthesis from lactosylceramide (By similarity). http://togogenome.org/gene/10090:Fam135a ^@ http://purl.uniprot.org/uniprot/Q6NS59 ^@ Similarity ^@ Belongs to the FAM135 family. http://togogenome.org/gene/10090:Vangl1 ^@ http://purl.uniprot.org/uniprot/Q80Z96 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Vang family.|||Cell membrane|||Heterodimer with Vangl2. Interacts through its C-terminal region with the N-terminal half of DVL1, DVL2 and DVL3. The PDZ domain of DVL1, DVL2 and DVL3 is required for the interaction. http://togogenome.org/gene/10090:Pes1 ^@ http://purl.uniprot.org/uniprot/Q9EQ61 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pescadillo family.|||Chromosome|||Component of the PeBoW complex, composed of BOP1, PES1 and WDR12 (PubMed:15225545). The complex is held together by BOP1, which interacts with PES1 via its N-terminal domain and with WDR12 via a high-affinity interaction between the seven-bladed beta-propeller domains of the 2 proteins. The PeBoW complex associates with the 66S pre-ribosome (By similarity). The PeBoW complex also associates with DDX27, PES1 interacts directly with DDX27 (By similarity). Interacts with IRS1 and UBTF (PubMed:15169904). May interact with MAP1B (PubMed:17308336).|||Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.|||Embryos die during preimplantation stages of development, with blastomeres failing to progress past morula stages. Within blastocysts the nucleoli fail to form correctly and the number of ribosomes appears dramatically reduced.|||In 2-cell and 4-cell stage interphase blastomeres expression is restricted to a sub-nuclear band that encircles one or more large vacuoles within the nucleus. These vacuoles may give rise to the mature nucleolus. Later in embryogenesis high levels are detected in developing liver. Is also widely and highly expressed throughout the developing brain and spinal cord at embryonic day 13.|||Induced in malignant astrocytes following the loss of p53. Induced in hepatocytes following partial hepatectomy.|||Sumoylated.|||Ubiquitous. Highest levels appear to be found in tissues that contain a population of proliferating cells, such as ovary and testis. Also appears to be highly expressed in kidney and liver. In the brain expression is restricted to neural progenitor cells and postmitotic neurons. Highly expressed in malignant astrocytes.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Chst15 ^@ http://purl.uniprot.org/uniprot/Q91XQ5 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sulfotransferase 1 family.|||Glycosylated.|||Golgi apparatus membrane|||Homodimer; disulfide-linked (Potential). The relevance of homodimerization is however unsure. May interact with phosphorylated proteins in resting B-cells, including HCK (By similarity).|||Inhibited by phenyl beta-GalNAc(4,6-SO(4)).|||Sulfotransferase that transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the C-6 hydroxyl group of the GalNAc 4-sulfate residue of chondroitin sulfate A and forms chondroitin sulfate E containing GlcA-GalNAc(4,6-SO(4)) repeating units. It also transfers sulfate to a unique non-reducing terminal sequence, GalNAc(4SO4)-GlcA(2SO4)-GalNAc(6SO4), to yield a highly sulfated structure similar to the structure found in thrombomodulin chondroitin sulfate. May also act as a B-cell receptor involved in BCR ligation-mediated early activation that mediate regulatory signals key to B-cell development and/or regulation of B-cell-specific RAG expression; however such results are unclear in vivo (By similarity). http://togogenome.org/gene/10090:Slc43a2 ^@ http://purl.uniprot.org/uniprot/Q8CGA3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Affinity and transport activity are regulated by a phosphorylation switch state at Ser-274 and Ser-297; increasing of affinity and amino acid transport activity via dephosphorylation at Ser-274 and phosphorylation at Ser-297.|||Basolateral cell membrane|||Belongs to the SLC43A transporter (TC 2.A.1.44) family.|||Cell membrane|||Dephosphorylation at Ser-274 and phosphorylation at Ser-297 increase affinity and amino acid transport activity (PubMed:30379325). Phosphorylation-dephosphorylation cycle is regulated by food-entrained diurnal rhythm and dietary proteins (PubMed:32470053).|||Expressed in intestine, kidney, brain and adipose tissue, heart and testis (PubMed:15659399). In the kidney, is detected in epithelial cells of the distal tubule and collecting duct (PubMed:15659399). In the intestine, is expressed mainly in crypt cells of the intestinal microvilli and epithelial cells in the base of the villus (PubMed:15659399). Expressed in small intestine enterocytes, the kidney proximal tubule, thick ascending limb and, to a minor extent, of distal convoluted tubule epithelial cells (PubMed:25480797).|||Glycosylated.|||Homozygous knockout fetuses mice for SLC43A2 display a reduced intrauterine growth not leading to a prenatal lethality. In addition, fetuses mice show a marked reduction in the concentration of almost all amino acids in the amniotic fluid (PubMed:25480797). Pups show growth defect, metabolic alterations and early postnatal lethality (PubMed:25480797).|||Regulated by protein diet.|||Uniporter that mediates the transport of the stereospecific L-phenylalanine, L-methionine and L-branched-chain amino acids, between the extracellular space and the cytoplasm and may control the transepithelial (re)absorption of neutral amino acid in kidney and small intestine (PubMed:25480797, PubMed:15659399). Transport activity is mediated through facilitated diffusion and is sodium ions-, chloride ions- and pH-independent (PubMed:25480797). http://togogenome.org/gene/10090:Cnot10 ^@ http://purl.uniprot.org/uniprot/Q8BH15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNOT10 family.|||Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is not required for association of CNOT7 to the CCR4-NOT complex (By similarity).|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. CNOT10 and CNOT11 form a subcomplex docked to the CNOT1 scaffold (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Zcchc7 ^@ http://purl.uniprot.org/uniprot/B1AX39 ^@ Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Component of a nucleolar TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes (By similarity).|||Probable cloning artifact.|||nucleolus http://togogenome.org/gene/10090:Ifna1 ^@ http://purl.uniprot.org/uniprot/A0A7R8GV68|||http://purl.uniprot.org/uniprot/P01572 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Glycosylated.|||Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.|||Secreted|||Was named interferon alpha-E (embryonic) based on peptide sequencing (PubMed:9244179). The differences found may be sequencing erros and have not been confirmed by other studies. http://togogenome.org/gene/10090:Actc1 ^@ http://purl.uniprot.org/uniprot/P68033|||http://purl.uniprot.org/uniprot/Q497E4 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.|||Belongs to the actin family.|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Methylated at His-75 by SETD3.|||Monomethylation at Lys-86 (K86me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.|||N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.|||Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.|||cytoskeleton http://togogenome.org/gene/10090:Mbd6 ^@ http://purl.uniprot.org/uniprot/Q3TY92 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds to heterochromatin. Does not interact with either methylated or unmethylated DNA (in vitro) (By similarity).|||Chromosome|||Detected in embryo from 7 to 17 dpc.|||Nucleus|||The MBD domain is necessary for chromocentric localization.|||Ubiquitous. Expressed at highest levels in adult testis and brain. http://togogenome.org/gene/10090:Gatd3a ^@ http://purl.uniprot.org/uniprot/Q9D172 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the GATD3 family.|||Mitochondrion http://togogenome.org/gene/10090:Taar8c ^@ http://purl.uniprot.org/uniprot/Q5QD05 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Cetn1 ^@ http://purl.uniprot.org/uniprot/P41209 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the centrin family.|||Binds two moles of calcium per mole of protein.|||Expressed in testis. Localizes to the caudal portion of spermatozoa in seminiferous tubule and epididymis (PubMed:10486202). Expressed in retina photoreceptor cells (at protein level) (PubMed:30120214).|||First expressed at 14 days postpartum (dpp). Levels increase dramatically between 14 dpp and 17 dpp.|||Monomer (By similarity). Interacts with CIMAP3 (PubMed:20643351).|||Plays a fundamental role in microtubule-organizing center structure and function (By similarity). Plays a role in sperm cilia formation (PubMed:27530713).|||centrosome|||cilium http://togogenome.org/gene/10090:Aim2 ^@ http://purl.uniprot.org/uniprot/Q91VJ1 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Also acts as a tumor suppressor independently of its role in inflammatory response (PubMed:26095253). Able to suppress overt cell proliferation in enterocytes: restricts stem cell proliferation in the intestinal mucosa in an inflammasome-independent manner, contributing to a decrease in the likelihood of colorectal cancer development (PubMed:26095253, PubMed:26107252). AIM2 suppresses cell proliferation by inhibiting phosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (PubMed:26095253, PubMed:26107252). Inhibits AKT1 phosphorylation both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (PubMed:26107252, PubMed:33505023). Also acts as a key regulator of regulatory T-cells (Treg) homeostasis by promoting their stability: acts by preventing AKT1 activation (PubMed:33505023). Its role in Treg homeostasis is important to restain autoimmune diseases (PubMed:33505023).|||Belongs to the HIN-200 family.|||By TGF-beta.|||Cytoplasm|||Degraded via selective autophagy following interaction with TRIM11.|||Expressed in developing neurons (PubMed:27561456). Highly expressed in regulatory T-cells (Treg) (PubMed:33505023).|||Inactive in absence of double-stranded DNA (dsDNA) (By similarity). Homooligomerizes upon binding to dsDNA, dsDNA serving as an oligomerization platform (By similarity). AIM2 requires large dsDNA to generate a structural template that couples dsDNA ligand-binding and homooligomerization (By similarity). Homooligomerization is followed by recruitment of PYCARD/ASC to initiate speck formation (nucleation) (By similarity). AIM2 and PYCARD/ASC homooligomer filaments assemble bidirectionally and the recognition between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner (By similarity). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (By similarity). Active CASP1 then specifically processes protein precursors, such as gasdermin-D (GSDMD), IL1B and IL18, leading to the release of mature cytokines in the extracellular milieu or pyroptosis, depending on cell type (PubMed:27846608, PubMed:32350463). AIM2 can be activated in response to events that cause genomic DNA (HIV protease inhibitor nelfinavir) or mitochondrial DNA release in the cytoplasm (such as Perfluoroalkyl substance pollutants or cholesterol overload) (PubMed:27462105, PubMed:29033131, PubMed:34006824). Activation of the AIM2 inflammasome is inhibited by IFI202 (PubMed:19131592, PubMed:23850291). Activation of the AIM2 inflammasome is inhibited by TRIM11, which promotes autophagy-dependent degradation of AIM2 (By similarity).|||Inflammasome|||Mice display defects in neuronal morphology and changes in behavior, characterized by lower locomotor activity, anxiety and reduced auditory fear memory (PubMed:27561456, PubMed:32350463). Mice are protected from pyroptosis of intestinal epithelial cells caused by acute ionizing and subsequent intestinal damage: in contrast to wild-type mice, crypts of Aim2-deficient mice maintain their integrity (PubMed:27846608). Mice develop more tumors in the colon in the azoxymethane and dextran sulfate sodium model of colorectal cancer (PubMed:26095253, PubMed:26107252).|||Nucleus|||Self-associates; forms homooligomers in response to cytosolic double-stranded DNA (dsDNA) and the dsDNA seems to serve as oligomerization platform (By similarity). Component of AIM2 inflammasome, which consists of a signal sensor component (AIM2), an adapter (PYCARD/ASC), which recruits an effector pro-inflammatory caspase (CASP1) (By similarity). Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction is direct (By similarity). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287). Interacts with EIF2AK2/PKR (By similarity). Interacts with MAPRE1 (By similarity). Interacts (via HIN-200 domain) with IFI202 (via HIN-200 domain 2); preventing activation of the AIM2 inflammasome (PubMed:19131592, PubMed:23850291). Interacts with RACK1; promoting association with PP2A phosphatase and dephosphorylation of AKT1 (PubMed:33505023). Interacts with TRIM11; promoting AIM2 recruitment to autophagosomes and autophagy-dependent degradation (By similarity).|||Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:19158679, PubMed:19131592, PubMed:20351692, PubMed:19158675, PubMed:19158676, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:32350463, PubMed:34006824, PubMed:23567559). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:19131592, PubMed:20351692, PubMed:19158675, PubMed:19158676, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559, PubMed:32350463). Acts as a recognition receptor (PRR): specifically recognizes and binds dsDNA in the cytosol, and mediates the formation of the inflammasome polymeric complex composed of AIM2, CASP1 and PYCARD/ASC (PubMed:19131592, PubMed:20351692, PubMed:19158675, PubMed:19158676, PubMed:20351693, PubMed:20417169, PubMed:20457908, PubMed:21902795, PubMed:23567559). Recruitment of pro-caspase-1 (proCASP1) to the AIM2 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion (PubMed:19158676). In some cells, CASP1 activation mediates cleavage and activation of GSDMD, triggering pyroptosis without promoting cytokine secretion (PubMed:27846608, PubMed:32350463). Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner (PubMed:19131592, PubMed:19158675, PubMed:20351692, PubMed:23567559). Involved in the DNA damage response caused by acute ionizing radiation by mediating pyroptosis of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks (PubMed:27846608). Mechanistically, AIM2 senses DNA damage in the nucleus to mediate inflammasome assembly and inflammatory cell death (PubMed:27846608). Also acts as a regulator of neurodevelopment via its role in the DNA damage response: acts by promoting neural cell death in response to DNA damage in the developing brain, thereby purging genetically compromised cells of the central nervous system (PubMed:32350463). Pyroptosis mediated by the AIM2 inflammasome in response to DNA damage is dependent on GSDMD without involving IL1B and IL18 cytokine secretion (PubMed:27846608, PubMed:32350463). Also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (PubMed:34471287). Can also trigger PYCARD/ASC-dependent, caspase-1-independent cell death that involves caspase-8 (CASP8) (PubMed:22555457).|||The HIN-200 domain mediates dsDNA binding via electrostatic interactions.|||The pyrin domain mediates homotypic interaction with PYCARD/ASC. http://togogenome.org/gene/10090:H2-K1 ^@ http://purl.uniprot.org/uniprot/P01901|||http://purl.uniprot.org/uniprot/Q3TH01|||http://purl.uniprot.org/uniprot/Q7JJ15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin).|||Involved in the presentation of foreign antigens to the immune system.|||Membrane http://togogenome.org/gene/10090:Hibch ^@ http://purl.uniprot.org/uniprot/Q8QZS1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Epc2 ^@ http://purl.uniprot.org/uniprot/Q8C0I4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the enhancer of polycomb family.|||May play a role in transcription or DNA repair.|||Nucleus http://togogenome.org/gene/10090:Or52l1 ^@ http://purl.uniprot.org/uniprot/Q7TRN7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Safb ^@ http://purl.uniprot.org/uniprot/D3YXK2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (By similarity). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (By similarity). Thereby acts as a negative regulator of cell proliferation (By similarity). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (PubMed:19403048).|||Monomer and homodimer (By similarity). Forms heterodimers with SAFB2 (By similarity). Interacts with KHDRBS3 (By similarity). Interacts with CLK2 (PubMed:11118435). Interacts with POLR2A, ASF/SRSF1, SRp30c/SRFS9 and TRA2B/SFRS10 (By similarity). Interacts with SRPK1 and inhibits its activity (By similarity). Interacts with RBMX (PubMed:19403048). Interacts with FUS (By similarity). Interacts with ZBED4 (By similarity).|||Nucleus|||Sumoylated by PIAS1 with SUMO1 and SUMO2/3, desumoylated by SENP1. Sumoylation is required for transcriptional repressor activity. http://togogenome.org/gene/10090:Or8g2b ^@ http://purl.uniprot.org/uniprot/Q9EQ96 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atraid ^@ http://purl.uniprot.org/uniprot/A8C1S6|||http://purl.uniprot.org/uniprot/Q6PGD0 ^@ Caution|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with NELL1; the interaction promotes osteoblastic differentiation and mineralization (By similarity). Interacts with SLC37A3; the interaction is direct and both proteins are mutually dependent for their stability (PubMed:29745899).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lysosome membrane|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus envelope|||Promotes osteoblast cell differentiation and terminal mineralization. Plays a role in inducing the cell cycle arrest via inhibiting CCND1 expression in all-trans-retinoic acid (ATRA) signal pathway (By similarity). In osteoclasts, forms a transporter complex with ATRAID for nitrogen-containing-bisphophonates (N-BPs) required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol (PubMed:29745899). http://togogenome.org/gene/10090:Dtx4 ^@ http://purl.uniprot.org/uniprot/Q6PDK8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Deltex family.|||Cytoplasm|||Expressed in brain, testis, embryonic fibroblasts and thymocytes.|||Functions as a ubiquitin ligase protein in vivo, mediating 'Lys48'-linked polyubiquitination and promoting degradation of TBK1, targeting to TBK1 requires interaction with NLRP4 (By similarity). Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations.|||Interacts with NLRP4.|||The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases. http://togogenome.org/gene/10090:Lcat ^@ http://purl.uniprot.org/uniprot/P16301 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4.|||Belongs to the AB hydrolase superfamily. Lipase family.|||Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs) (PubMed:19065001). The cholesterol ester is then transported back to the liver. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels (PubMed:19065001). Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins (PubMed:19065001). Required for remodeling high-density lipoprotein particles into their spherical forms (PubMed:19065001). Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines (PubMed:8820107). Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:10393212). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF (By similarity). Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters (By similarity).|||Detected in blood plasma (PubMed:8820107). Produced and secreted by astrocytes (at protein level) (PubMed:19065001). Abundantly expressed in liver, brain and testis with highest levels in liver. In the brain, found in cerebellum, cerebral cortex, hippocampus and brain stem. Located to neurons and neuroglia.|||In the testis, expressed days 4,8, 14, and 35 of postnatal life with highest levels at day 35. In the brain, expressed in fetal stages and levels begin to rise after day 4 after birth and continue to increase through suckling and weaning reaching a peak at postnatal day 24. In the liver, expressed in fetal life from day 16-21 of gestation with a 3-fold increase in the four final days of gestation.|||Null mice exhibit a 7-fold increase in the cholesteryl ester fatty acid CEFA ratio of APOB lipoprotein CEs. There is also a 3.6 increase in vascular ring O(2) production and plasma phospholipid (PL)-bound-F2-isoprostane levels. This effect is paradoxically reversed in the APOE knockout background (PubMed:11809774, PubMed:11893779). Mice show a significant reduction in total cholesterol, HDL-cholesterol, apoA-I, serum paraoxonase and PAF acetylhydrolase enzyme activities and show a modest (36%) but significant increase in apoJ levels (PubMed:10393212).|||Secreted http://togogenome.org/gene/10090:Slc7a10 ^@ http://purl.uniprot.org/uniprot/P63115 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with SLC3A2/4F2hc to form a functional heterodimeric complex that translocates small neutral L- and D-amino acids across the plasma membrane. Preferentially mediates exchange transport, but can also operate via facilitated diffusion (PubMed:10734121) (By similarity). Acts as a major transporter for glycine, L- and D-serine in the central nervous system. At the spinal cord and brainstem regulates glycine metabolism and glycinergic inhibitory neurotransmission by providing for glycine de novo synthesis from L-serine and glycine recycling from astrocytes to glycinergic motor neurons (PubMed:25755256, PubMed:27759100). At Schaffer collateral-CA1 synapses mediates D-serine and glycine release that modulates post-synaptic activation of NMDA receptors and excitatory glutamatergic transmission (By similarity). May regulate D-serine release from mesenchymal progenitors located in developing subcutaneous adipose tissue, favoring white adipocyte over thermogenic beige adipocyte lineage commitment (PubMed:33707431).|||Belongs to the amino acid-polyamine-organocation (APC) superfamily.|||Cell membrane|||Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.|||Highly expressed in brain and lung, and to a lesser extent in placenta and small intestine (PubMed:10734121). Expressed in a subpopulation of astrocytes enriched at glycinergic synapses in the spinal cord and brainstem (at protein level). Expressed in OLIG2-positive astrocytes of the lateral globus pallidus (at protein level) (PubMed:27759100, PubMed:34749773). Expressed in CD34-positive, DPP4-positive mesenchymal progenitors in developing subcutaneous adipose tissue (PubMed:33707431).|||Mutant mice develop hyperekplexia-like phenotype due to impaired glycinergic inhibitory transmission. Administration of glycine and L-serine reverses the phenotype.|||Up-regulated upon adipocyte differentiation in response to INS. Down-regulated by treatment with rosiglitazone. http://togogenome.org/gene/10090:Recql5 ^@ http://purl.uniprot.org/uniprot/Q8VID5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. RecQ subfamily.|||DNA helicase that plays an important role in DNA replication, transcription and repair. Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability. Associates also with POLR1A and enforces the stability of ribosomal DNA arrays. Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress. Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis. Required for efficient DNA repair, including repair of inter-strand cross-links. Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination.|||Monomer. Interacts with TOP2A, TOP3A and TOP3B. Interacts with RNA polymerase II subunit POLR2A. Identified in a complex with the RNA polymerase II core bound to DNA. Interacts with RAD51 (By similarity). Interacts with WRN; this interaction stimulates WRN helicase activity on DNA fork duplexes (By similarity). Interacts with MUS1; this interaction promotes MUS81-dependent mitotic DNA synthesis (By similarity).|||Phosphorylated by CDK1 at Ser-728; this phosphorylation is required for RECQL5-mediated disruption of RAD51 filaments on stalled replication forks.|||nucleoplasm http://togogenome.org/gene/10090:Baiap2l1 ^@ http://purl.uniprot.org/uniprot/Q9DBJ3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in bladder, liver, testes, heart, lung, spleen, brain and skeletal muscle (at protein level).|||Interacts with RAC1. Binds to F-actin. Interacts with FASLG (By similarity).|||May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection (By similarity).|||Phosphorylated on tyrosine in response to insulin.|||The IMD domain is predicted to have a helical structure. It may induce actin bundling and filopodia formation (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Cers5 ^@ http://purl.uniprot.org/uniprot/Q9D6K9 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ According to a report, deletion of Cers5 protects from obesity: knockout mice are associated with reduced weight gain and improved systemic health after high fat diet challenge (PubMed:26853464). This result was however not confirmed by another study, which did not observe any protection from diet-induced obesity in knockout mice (PubMed:31150623). Effects observed in the first study might be indirect and caused by a large deletion that affects neighboring genes and/or deletes non-coding RNAs (PubMed:26853464, PubMed:31150623).|||Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) (PubMed:12912983, PubMed:15823095, PubMed:16100120, PubMed:17977534, PubMed:17609214, PubMed:26853464). Can use other acyl donors, but with less efficiency (PubMed:15823095). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:12912983, PubMed:15823095, PubMed:15772421, PubMed:17977534). Plays a role in de novo ceramide synthesis and surfactant homeostasis in pulmonary epithelia (PubMed:15772421).|||Endoplasmic reticulum membrane|||Expressed in lungs of 15 days old fetuses followed by a modest peak at day 17, thereafter decreasing in adult lungs.|||Inhibited by fumonisin B1.|||Mice are viable and show no apparent morphological alterations in normal conditions (PubMed:26853464). Decreased palmitoyl (C16:0) ceramide pools (PubMed:26853464).|||Phosphorylated at the C-terminus by CK2.|||Some prediction bioinformatics tools predict the presence of a homeobox domain (By similarity). However, the domain is degenerate and residues that are important for DNA-binding are absent (By similarity). Moreover, the protein localizes in the endoplasmic reticulum and not in the nucleus, strongly suggesting that it does not constitute a canonical homeobox domain (PubMed:12912983).|||The last loop motif confers selectivity toward palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA) as acyl donor.|||Ubiquitously expressed, with highest levels in testis and kidney (PubMed:12912983, PubMed:15823095). Expressed in pulmonary epithelia (PubMed:15772421). http://togogenome.org/gene/10090:Cd300ld ^@ http://purl.uniprot.org/uniprot/Q8VCH2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Acts as a functional murine norovirus (MNV) receptor. Primary determinant of MNV species tropism and is sufficient to render cells permissive to infection by MNV. Can render nonmurine mammalian cells susceptible to MNV infection (PubMed:27681626, PubMed:27540007).|||Acts as an activating receptor in myeloid cells and mast cells.|||Belongs to the CD300 family.|||Cell membrane|||Expressed in dendritic cells, macrophages and granulocytes. Present on the surface of granulocytes and monocytes/macrophages (at protein level).|||Interacts with FCER1G.|||O-glycosylated. http://togogenome.org/gene/10090:Vmn1r233 ^@ http://purl.uniprot.org/uniprot/Q8R294 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pnma3 ^@ http://purl.uniprot.org/uniprot/Q8JZW8 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PNMA family.|||Expressed in the cerebrum and cerebellum.|||nucleolus http://togogenome.org/gene/10090:Madd ^@ http://purl.uniprot.org/uniprot/A0A0R4J1F4|||http://purl.uniprot.org/uniprot/A2AGR0|||http://purl.uniprot.org/uniprot/E9QN47|||http://purl.uniprot.org/uniprot/Q80U28 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apparently normal in utero development but immediate death after birth, probably due acute respiratory failure (PubMed:11359932). Absent GDP/GTP exchange activity of Rab3A (PubMed:11359932). Apparently normal development of the central nervous system during embryonic stages (PubMed:11359932). At 18.5 dpc, no evoked action potentials of the diaphragm and gastrocnemius muscles in response to electrical stimulation of the phrenic and sciatic nerves, respectively. In contrast, axonal conduction of the spinal cord and the phrenic nerve are not impaired. Reduced total numbers of synaptic vesicles at the neuromuscular junction, especially those docked at the presynaptic plasma membrane, whereas postsynaptic structures and functions appear normal (PubMed:11359932). Reduction of excitatory postsynaptic current amplitude in neurons (PubMed:12388783). Synaptic vesicles locate remote from the presynaptic membrane in the central region instead of at the active zones of the presynaptic terminal (PubMed:12388783). RNAi-mediated knockdown results in reduced levels of Rab27a in the activated GTP-bound form (PubMed:18559336). In melanocytes, results in aggregation and perinuclear clustering of melanosomes (PubMed:18559336). RNAi-mediated knockdown in hippocampal neurons leads reduced interaction between Kif1b and Rab3 and to reduced axonal transport of Rab3 (PubMed:18849981).|||Belongs to the MADD family.|||Cell membrane|||Cytoplasm|||Expressed in the brain.|||Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:11359932). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (PubMed:11359932, PubMed:12388783, PubMed:18849981). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (PubMed:12388783). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (PubMed:18849981). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (By similarity). May link TNFRSF1A with MAP kinase activation (By similarity). May be involved in the regulation of TNFA-induced apoptosis (By similarity).|||Interacts (via death domain) with TNFRSF1A (via death domain) (By similarity). Interacts with PIDD1 (By similarity). Interacts with YWHAZ (By similarity). Interacts (via death domain) with KIF1B (PubMed:18849981). Interacts with KIF1A (PubMed:18849981). Interacts (via uDENN domain) with RAB3A, RAB3B, RAB3C and RAB3D; the GTP-bound form of the Rab proteins is preferred for interaction (PubMed:18849981).|||Membrane|||axon http://togogenome.org/gene/10090:Trpc2 ^@ http://purl.uniprot.org/uniprot/Q9R244 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC2 sub-subfamily.|||Isoform 3 is ubiquitously expressed at low levels. Isoform 4 is expressed exclusively in vomeronasal organ.|||Membrane|||Reduced electrophysiological response to pheromone mixtures in the vomeronasal organ. Mutant males and nursing females are docile and fail to initiate aggressive attacks on intruder males. Males display normal mating behavior towards females but display increased sexual behavior towards prepubescent females even when presented simultaneously with adult estrus females and also show increased sexual behavior towards juvenile and adult males. Lack of response to Esp1.|||Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. May also be activated by intracellular calcium store depletion. Plays a role in mediating responsivity to pheromones that elicit aggressive and mating behaviors. Required for response to the Esp1 pheromone which enhances female sexual receptive behavior and to the Esp22 pheromone which inhibits adult male mating behavior. http://togogenome.org/gene/10090:Ifi27 ^@ http://purl.uniprot.org/uniprot/E9Q1C5|||http://purl.uniprot.org/uniprot/Q70LM9|||http://purl.uniprot.org/uniprot/Q70LN0|||http://purl.uniprot.org/uniprot/Q8C6G0|||http://purl.uniprot.org/uniprot/Q9D1E1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the IFI6/IFI27 family.|||Membrane http://togogenome.org/gene/10090:Or52e8b ^@ http://purl.uniprot.org/uniprot/Q7TRP1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mmp9 ^@ http://purl.uniprot.org/uniprot/P41245 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Induced in macrophages as well as in whole animals (spleen, lung and liver) by incubation or infection with M.bovis BCG and M.tuberculosis H37Rv (at protein level) (PubMed:11500442).|||Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 3 Ca(2+) ions per subunit.|||Exists as monomer or homodimer; disulfide-linked. Exists also as heterodimer with LCN2. Macrophages and transformed cell lines produce only the monomeric form. Interacts with ECM1.|||Inhibited by histatin-3 1/24 (histatin-5). Inhibited by ECM1.|||Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (PubMed:8132709). Cleaves KiSS1 at a Gly-|-Leu bond (By similarity). Cleaves NINJ1 to generate the Secreted ninjurin-1 form (PubMed:23142597, PubMed:32883094). Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide (By similarity).|||N- and O-glycosylated.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||Up-regulated by ARHGEF4, SPATA13 and APC via the JNK signaling pathway in colorectal tumor cells.|||extracellular matrix http://togogenome.org/gene/10090:Peg10 ^@ http://purl.uniprot.org/uniprot/Q7TN75 ^@ Biotechnology|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can be reprogrammed to form virion-like capsids that deliver engineered cargo mRNAs bearing RNA signals from PEG10 5'- and 3'-UTR into target cells.|||Cytoplasm|||Embryonic lethality resulting from placental defects.|||Expressed in a subset of adult tissues, including brain and testis (PubMed:11574691, PubMed:30951545). Expressed during the early process of adipocyte differentiation (PubMed:17707377). Expressed weakly in mammary gland but strongly in breast carcinomas of a c-MYC-driven transgenic model (PubMed:16423995).|||Expressed in adrenal gland, testis and placenta (PubMed:30951545). Present at lower level in pituitary, ovary, uterus, white adipose, brain and lung (PubMed:30951545).|||Expressed in embryo, placenta and amniotic membrane at 10.5 dpc (PubMed:17942406, PubMed:25888968). Expressed in placenta at 9.5 dpc and appeared to increase as gestation progresses peaking around 12.5 and 15.5 dpc (at protein level) (PubMed:16341224, PubMed:25888968). Expressed in embryo at 9.5, 12.5 and 16.5 dpc (PubMed:11574691). Expressed in developing musculo-skeletal system, during skeletal myogenesis and also in precartilage primordia and derivative chondrogenic cells of the developing skeleton (PubMed:11574691). Expressed in mesenchymal tissues of developing lung, kidney, gonad, gut and placenta (PubMed:11574691). Not expressed at stages of chondrocyte hypertrophy and ossification of bones (PubMed:11574691). Expressed in all extraembryonic tissues at 9.5 and 12.5 dpc and low-level expression in the embryonic brain and vertebral cartilage at 12.5 dpc (PubMed:11574691).|||Extracellular vesicle membrane|||Homooligomer; homooligomerizes into virion-like capsids (PubMed:34413232). Interacts with ACVRL1 (By similarity). Interacts with SIAH1 and SIAH2 (By similarity).|||In addition to the capsid (CA) and nucleocapsid (NC) subdomains of gag proteins, this isoform contains subdomains of pol, namely a protease (PRO) domain and a predicted reverse transcriptase (RT)-like domain.|||Nucleus|||Produced by a -1 ribosomal frameshifting due to a slippery site occurring between the codons for Gly-370 and Lys-371.|||Produced by conventional translation.|||Retrotransposon-derived protein that binds its own mRNA and self-assembles into virion-like capsids (PubMed:30951545, PubMed:34413232). Forms virion-like extracellular vesicles that encapsulate their own mRNA and are released from cells, enabling intercellular transfer of PEG10 mRNA (PubMed:34413232). Binds its own mRNA in the 5'-UTR region, in the region near the boundary between the nucleocapsid (NC) and protease (PRO) coding sequences and in the beginning of the 3'-UTR region (PubMed:34413232). Involved in placenta formation: required for trophoblast stem cells differentiation (PubMed:16341224, PubMed:30951545). Involved at the immediate early stage of adipocyte differentiation (PubMed:17707377). Overexpressed in many cancers and enhances tumor progression: promotes cell proliferation by driving cell cycle progression from G0/G1 (By similarity). Enhances cancer progression by inhibiting the TGF-beta signaling, possibly via interaction with the TGF-beta receptor ACVRL1 (By similarity). May bind to the 5'-GCCTGTCTTT-3' DNA sequence of the MB1 domain in the myelin basic protein (MBP) promoter; additional evidences are however required to confirm this result (PubMed:9473521).|||The PEG10 locus is imprinted, giving rise to paternally expressed proteins.|||The protein is evolutionarily related to retrotransposon Gag proteins: it contains the capsid (CA) and nucleocapsid (NC) subdomains of gag.|||Ubiquitinated (PubMed:30951545). Deubiquitinated at Lys-362 and Lys-365 by USP9X (PubMed:30951545).|||Undergoes proteolytic cleavage.|||Up-regulated by MYC and during adipocyte differentiation. http://togogenome.org/gene/10090:Zfp57 ^@ http://purl.uniprot.org/uniprot/Q8C6P8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Affects the maintenance of DNA methylation imprints. The absence of just the zygotic function causes partial neonatal lethality, whereas eliminating both the maternal and zygotic functions results in a highly penetrant embryonic lethality. In oocytes, its absence results in failure to establish maternal methylation imprints at the Snrpn imprinted region. Intriguingly, methylation imprints are reacquired specifically at the maternally derived Snrpn imprinted region when the zygotic Zfp57 is present in embryos (PubMed:18854139, PubMed:30602440). Double zygotic mutations of ZFP57 and ZNF445 are embryonically lethal and embryos show no gross morphological abnormalities but significant reduction in size and weight at 11.5 dpc, a phenotype more pronounced than in ZFP57 mutant mice with a more severe loss of impinting (PubMed:30602440).|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in oocytes and in a subset of adult tissues. Expressed at high levels in testis, and at low levels in cerebellum. Present in sciatic nerve and spinal cord (at protein level).|||Expression peaks between 11 dpc and 17 dpc, and decreases from P0 to P28. Expressed in lung throughout embryonic development. At 12 dpc, expressed in spinal cord, dorsal root ganglia and sciatic nerve. At 15 dpc, highly expressed in all neural tissues. At P0, expressed in brain and spinal cord. Present in Schwann cells at 16 dpc and P0 (at protein level). Maternal product is present in preimplantation embryos. Expressed in pluripotent embryonic stem cells. Down-regulated when embryonic stem cells differentiate.|||Nucleus|||Numerous sequencing errors.|||The KRAB domain is required for function as transcriptional repressor.|||Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions (ICRs) (PubMed:15070898, PubMed:18854139, PubMed:23059534, PubMed:30602440). Acts together with ZNF445, but ZFP57 plays the predominant role in imprinting maintenance. In contrast, in humans, ZNF445 seems to be the major factor early embryonic imprinting maintenance (PubMed:30602440). Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element (PubMed:15070898, PubMed:18854139, PubMed:23059534).|||Up-regulated by LIF. Down-regulated during differentiation of embryonic stem cells, or during retinoic acid-induced differentiation of F9 cells (at protein level). Regulated by JMJD1A, which mediates histone H3K9Me2 demethylation at its promoter, thereby activating expression.|||Zinc fingers 2 and 3 mediate recognition of the target element, ZF2 interacting with the 5' half (TGC) and ZF3 interacting with the 3' half (CGC). http://togogenome.org/gene/10090:Csf1 ^@ http://purl.uniprot.org/uniprot/P07141 ^@ Caution|||Disease Annotation|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ A defect in Csf1 is the cause of osteopetrosis. Osteopetrotic mice (op/op) are severely deficient in mature macrophages and osteoclasts, display failed tooth eruption, and have a restricted capacity for bone remodeling.|||Cell membrane|||Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.|||Homodimer or heterodimer; disulfide-linked (PubMed:19017797). Likely to exist in multiple forms: homodimer consisting of 2 identical 150-200 kDa proteoglycan subunits, heterodimer consisting of a 150-200 kDa proteoglycan subunit and a truncated 43 kDa subunit, and homodimer consisting of 2 identical 43 kDa subunits (By similarity). Interacts with CSF1R (PubMed:19017797).|||N-glycosylated.|||O-glycosylated; contains chondroitin sulfate.|||The sequence reported in PubMed:8357831 was thought to originate from rat, but was later shown (PubMed:12074592, PubMed:12379742) to be derived from mouse.|||extracellular space http://togogenome.org/gene/10090:Immp1l ^@ http://purl.uniprot.org/uniprot/Q9CQU8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S26 family. IMP1 subfamily.|||Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO (By similarity).|||Heterodimer of 2 subunits, IMMPL1 and IMMPL2.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:2310057N15Rik ^@ http://purl.uniprot.org/uniprot/Q9D6T8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Apoa5 ^@ http://purl.uniprot.org/uniprot/Q8C7G5 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the apolipoprotein A1/A4/E family.|||Early endosome|||Induced in early phase of liver regeneration.|||Interacts with GPIHBP1 (By similarity). Interacts with SORL1; this interaction leads to APOA5 internalization and sorting either to lysosomes and degradation, or to the trans-Golgi network (By similarity).|||Late endosome|||Liver.|||Mice expressing the human APOAV transgene show a decrease in plasma TG by one third. Conversely, knockout mice lacking APOAV have a four time increase in plasma TG.|||Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL. May also be associated with chylomicrons. Important determinant of plasma triglyceride (TG) levels by both being a potent stimulator of apo-CII lipoprotein lipase (LPL) TG hydrolysis and an inhibitor of the hepatic VLDL-TG production rate (without affecting the VLDL-apoB production rate). Activates poorly lecithin:cholesterol acyltransferase (LCAT) and does not enhance efflux of cholesterol from macrophages (By similarity). Binds heparin (By similarity).|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted|||trans-Golgi network http://togogenome.org/gene/10090:Zmynd11 ^@ http://purl.uniprot.org/uniprot/Q8R5C8 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromatin reader that specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and regulates RNA polymerase II elongation. Does not bind other histone H3 subtypes (H3.1 or H3.2). Colocalizes with highly expressed genes and functions as a transcription corepressor by modulating RNA polymerase II at the elongation stage (PubMed:24590075). Binds non-specifically to dsDNA (By similarity). Acts as a tumor-suppressor by repressing a transcriptional program essential for tumor cell growth (PubMed:24590075).|||Chromosome|||Homooligomer; forms homooligomers via its C-terminus. Interacts with histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3). Interacts (via MYND-type zinc finger) with NCOR1. Interacts (via MYND-type zinc finger) with MGA protein (via PXLXP motif). Interacts (via MYND-type zinc finger) with EZH2. Interacts with EMSY and E2F6. Interacts with PIAS1 and UBE2I (By similarity).|||Nucleus|||Sumoylated following its interaction with PIAS1 and UBE2I.|||The PWWP domain specifically recognizes and binds histone H3.3 trimethylated at 'Lys-36' (H3.3K36me3) and adopts a five-bladed beta-barrel fold with an extended C-terminal alpha-helix, with a conserved H3.3K36me3-binding aromatic cage formed by Phe-291 and Trp-294 of the beta1-beta2 loop and Phe-310 of the beta3-beta4 loop. Specific recognition of H3.3 histone is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains (PubMed:24590075).|||Ubiquitinated, leading to proteasomal degradation. http://togogenome.org/gene/10090:Polr3gl ^@ http://purl.uniprot.org/uniprot/D3YXS1|||http://purl.uniprot.org/uniprot/Q8R0C0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic RPC7 RNA polymerase subunit family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits (By similarity). Found a trimeric complex with POLR3C and POLR3G. Directly interacts with POLR3C (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.|||Expressed in the liver.|||Nucleus http://togogenome.org/gene/10090:Tbc1d17 ^@ http://purl.uniprot.org/uniprot/Q8BYH7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with OPTN; this interaction mediates TBC1D17 transient association with Rab8.|||Probable GTPase-activating protein that inhibits RAB8A/B function. Reduces Rab8 recruitment to tubules emanating from the endocytic recycling compartment (ERC) and inhibits Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TfR). Involved in regulation of autophagy.|||Recycling endosome|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.|||autophagosome http://togogenome.org/gene/10090:Ooep ^@ http://purl.uniprot.org/uniprot/Q9CWE6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25 to DNA replication forks, thereby promoting the ubiquitination of BLM by TRIM25, enhancing BLM retainment at replication forks and therefore promoting stalled replication fork restart (PubMed:29125140). Positively regulates the homologous recombination-mediated DNA double-strand break (DSB) repair pathway by regulating ATM activation and RAD51 recruitment to DSBs in oocytes (PubMed:29955025). Thereby contributes to oocyte survival and the resumption and completion of meiosis (PubMed:29955025). As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:18804437, PubMed:25208553). Required for the formation of F-actin cytoplasmic lattices in oocytes which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning (PubMed:25208553).|||Belongs to the KHDC1 family.|||Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and TLE6 (PubMed:18804437, PubMed:28992324). Within the complex, interacts with NLRP5, KHDC3 and TLE6 (PubMed:18804437, PubMed:31575650). The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments (By similarity). As part of the SCMC interacts with the SCMC-associated protein NLRP4F (PubMed:31575650). Forms a scaffold complex with KHDC3/FILIA, and interacts with BLM and TRIM25 at DNA replication forks (PubMed:29125140).|||Contains an atypical KH domain with amino acid changes at critical sites, suggesting that it may not bind RNA.|||Cytoplasm|||Embryonic death at 2.5 dpc (PubMed:18804437). Progression from embryonic 1- to 2-cell stage delayed 6-8 hours. Less than 20% of the embryos progress beyond 2-cell stage (PubMed:18804437). Embryos form unequal sized blastomeres due to smaller, dysmorphic, and displaced mitotic spindles resulting in asymmetric division (PubMed:25208553). Decrease in thickness of subcortical F-actin in zygotes, thickening of F-actin bundles in the cytoplasm and loss of F-actin cytoplasmic lattices (PubMed:25208553). Decrease in CFL1/Cofilin-1 expression in the subcortex and diffused distribution in the cytoplasm of zygotes (PubMed:25208553). Decrease in expression of the SCMC component ZBED3 in oocytes (PubMed:28992324). Oocytes exhibit greater amounts of DNA damage and show an inability to repair DNA double strand breaks (PubMed:29955025). Increase in oocyte apoptosis upon treatment with the DNA cross-linking agent cisplatin (PubMed:29955025). Increased number of oocytes in primordial and primary follicles in 4 week old mice, however this number is decreased in 16 week old mice (PubMed:29955025). 4 hour delay in reaching 50% germinal vesicle breakdown (GVB) with a 20% decrease in the number of oocytes that complete GVB. 2 hour delay in reaching 50% polar body extrusion (PBE) with a decrease of 20% in the number of oocytes that complete PBE (PubMed:29955025).|||Expressed in ovaries, where it is restricted to growing oocytes, with greatest levels in fully grown oocytes.|||Induced by etoposide.|||Nucleus|||Transcripts first detected at 15.5 dpc and peak 1 week after birth (PubMed:18804437). Transcripts accumulate during oogenesis (PubMed:18804437). During meiotic maturation, the vast majority of the transcripts are degraded and virtually none is detected by 2-cell stage embryogenesis (PubMed:18804437). The protein however persists during preimplantation up to the blastocyst stage (PubMed:18804437). At 2-cell stage, excluded from cell-cell contact regions (PubMed:18804437). Continuous exclusion from these regions during preimplantation development leads to the absence of the protein from the inner cells of the morula and the inner cell mass of the blastocyst (PubMed:18804437). Expressed in ovaries at postnatal day 2 (P2), expression peaks at P10, expression is then slightly decreased at P17 and further decreased at P21 (PubMed:31575650). http://togogenome.org/gene/10090:Cep63 ^@ http://purl.uniprot.org/uniprot/F8VPJ7|||http://purl.uniprot.org/uniprot/U5KVR9 ^@ Similarity ^@ Belongs to the CEP63 family. http://togogenome.org/gene/10090:Cep170b ^@ http://purl.uniprot.org/uniprot/Q80U49 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CEP170 family.|||Plays a role in microtubule organization.|||cytoskeleton http://togogenome.org/gene/10090:Cplx2 ^@ http://purl.uniprot.org/uniprot/P84086 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the complexin/synaphin family.|||Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.|||In the brain, expression starts at P6 and increases to reach a plateau at P20.|||Mice show no obvious phenotypic changes and no significant motor deficiencies. However, they show abnormalities in a number of complex behaviors including exploration, socialization, motor coordination, learning and reversal learning.|||Negatively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles (PubMed:11163241, PubMed:23345244). Also involved in mast cell exocytosis (PubMed:11163241). Although not essential for development, seems critical for the acquisition of higher cognitive functions in the adult brain (PubMed:12915444).|||Nervous system. Expressed predominantly in brain, where it is present in many regions, including hippocampus and cerebellum. In the retina, present at conventional amacrine cell synapses (at protein level).|||Nucleus|||Perikaryon|||Presynapse|||cytosol http://togogenome.org/gene/10090:Nudt19 ^@ http://purl.uniprot.org/uniprot/P11930 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family.|||By testosterone.|||Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate (PubMed:16185196, PubMed:29378847). Mediates the hydrolysis of a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters and at low substrate concentrations medium and long-chain fatty-acyl-CoA esters are the primary substrates (PubMed:16185196, PubMed:29378847). Highest activity seen with medium-chain acyl-CoA esters and higher rates of activity seen with the unsaturated acyl-CoA esters compared with the saturated esters (PubMed:16185196). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (PubMed:32432673).|||Highly expressed in the kidneys, with lower levels in skeletal muscle and brain (at protein level).|||Inhibited by chenodeoxycholic acid (CDCA) and its conjugated derivatives, taurochenodeoxycholic acid and glycochenodeoxycholic acid (PubMed:29378847). Inhibited by fluoride (PubMed:16185196).|||Mice exhibit a significant 20% increase in total CoA levels in kidney.|||Monomer.|||Peroxisome http://togogenome.org/gene/10090:Dazap2 ^@ http://purl.uniprot.org/uniprot/Q9DCP9 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Between 11.5 dpc and 12.5 dpc it is specifically expressed in the developing heart. From 13.5 dpc, expression in the heart disappears, while it becomes strongly expressed in the brain. Up-regulated during adhesion and differentiation to beating cardiomyocytes.|||By serum stimulation.|||Cytoplasm|||Following DNA damage, phosphorylated by HIPK2 which promotes DAZAP2 localization to the nucleus, reduces interaction of DAZAP2 with HIPK2 and SIAH1, and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent HIPK2 proteasomal degradation.|||In unstressed cells, promotes SIAH1-mediated polyubiquitination and degradation of the serine/threonine-protein kinase HIPK2, probably by acting as a loading factor that potentiates complex formation between HIPK2 and ubiquitin ligase SIAH1 (By similarity). In response to DNA damage, localizes to the nucleus following phosphorylation by HIPK2 and modulates the expression of a subset of TP53/p53 target genes by binding to TP53 at target gene promoters (By similarity). This limits the expression of a number of cell death-mediating TP53 target genes, reducing DNA damage-induced cell death (By similarity). Enhances the binding of transcription factor TCF7L2/TCF4, a Wnt signaling pathway effector, to the promoters of target genes (PubMed:19304756). Plays a role in stress granule formation (By similarity).|||Interacts with SOX6 (PubMed:14530442). Interacts with DAZ1 and DAZL (By similarity). Interacts with IL17RB (By similarity). May interact with FAM168B (By similarity). Interacts with INCA1 (By similarity). Interacts with EIF4G1 and EIF4G2 (By similarity). Interacts (via PPAY motif) with NEDD4 (via WW domains) (By similarity). Interacts with transcription factor TCF4; the interaction results in localization of DAZAP2 to the nucleus (By similarity). Interacts with transcription factors TCF7 and TCF7L1 (By similarity). Interacts with transcription factor LEF1 (PubMed:19304756). Interacts with serine/threonine-protein kinase HIPK2; the interaction results in phosphorylation of DAZAP2 which causes localization of DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent degradation of HIPK2 (By similarity). Interacts with ubiquitin ligase SIAH1; the interaction is decreased following phosphorylation of DAZAP2 by HIPK2 (By similarity). Interacts with TP53; the interaction is triggered by DNA damage (By similarity).|||Nucleus|||Nucleus speckle|||Stress granule|||Ubiquitinated by SMURF2, leading to proteasomal degradation. Ubiquitinated by NEDD4, leading to proteasomal degradation.|||Widely expressed (PubMed:14530442, PubMed:19304756). Highly expressed in brain (PubMed:10373015).|||nuclear body http://togogenome.org/gene/10090:Appl1 ^@ http://purl.uniprot.org/uniprot/Q8K3H0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Early endosome membrane|||Endosome|||Expressed in insulin-target tissues including skeletal muscle, liver, fat, and brain.|||Homodimer. Binds RAB5A/Rab5 through an N-terminal domain. This interaction is essential for its recruitment to endosomal membranes as well as its role in cell proliferation. Binds DCC and the catalytic domain of the inactive form of AKT2 through its PID domain. Binds PIK3CA and subunits of the NuRD/MeCP1 complex (By similarity). Interacts with OCRL and INPP5B (PubMed:20133602) (By similarity). Interacts with NTRK2 (PubMed:21849472). Interacts with APPL2; interaction is independent of follicle stimulating hormone stimulation; interaction is decreased by adiponectin in a time-dependent manner (PubMed:25328665). Forms a complex with APPL2 and RUVBL2. Forms a complex comprising APPL2, RUVBL2, CTNNB1, HDAC1 and HDAC2; interaction reduces interaction between CTNNB1, HDAC1, HDAC2 and RUVBL2 leading to the decrease of deacetylase activity of this complex; affects the recruitment of repressive complexes to the Wnt target genes. Interacts with ANXA2. Interacts with TGFBR1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner. Interacts with PRKCZ (By similarity). Interacts with PIK3R1 and APPL2 (PubMed:25328665). Interacts with ADIPOR1; ADIPOQ enhances this interaction; inhibites adiponectin-stimulated binding of APPL2 to ADIPOR1 (PubMed:19661063).|||Multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism (By similarity) (PubMed:25328665, PubMed:25568335, PubMed:27219021). Regulates signaling pathway leading to cell proliferation through interaction with RAB5A and subunits of the NuRD/MeCP1 complex (By similarity). Functions as a positive regulator of innate immune response via activation of AKT1 signaling pathway by forming a complex with APPL1 and PIK3R1 (PubMed:25328665). Inhibits Fc-gamma receptor-mediated phagocytosis through PI3K/Akt signaling in macrophages (PubMed:25568335). Regulates TLR4 signaling in activated macrophages (PubMed:27219021). Involved in trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner. Plays a role in cell metabolism by regulating adiponecting and insulin signaling pathways (By similarity). Required for fibroblast migration through HGF cell signaling (PubMed:26445298). Positive regulator of beta-catenin/TCF-dependent transcription through direct interaction with RUVBL2/reptin resulting in the relief of RUVBL2-mediated repression of beta-catenin/TCF target genes by modulating the interactions within the beta-catenin-reptin-HDAC complex (By similarity).|||Nucleus|||Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-707) has a proapoptotic effect.|||Phosphorylation at Ser-410 by PKA severely impairs binding to OCRL.|||Reduced survival rate after injection of LPS (PubMed:25328665). Appl1 and Appl2 double knockout mice are viable and grossly normal with regard to reproductive potential and postnatal growth (PubMed:26445298).|||The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B.|||phagosome|||ruffle http://togogenome.org/gene/10090:Spem2 ^@ http://purl.uniprot.org/uniprot/Q8C5U4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or5t9 ^@ http://purl.uniprot.org/uniprot/Q0VAY0|||http://purl.uniprot.org/uniprot/Q8VF13 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Stard10 ^@ http://purl.uniprot.org/uniprot/Q9JMD3 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||During male germ cell development, it was detected first in the 23-day-old mouse testis, and the signal increased with age.|||Membrane|||Phospholipid transfer protein that preferentially selects lipid species containing a palmitoyl or stearoyl chain on the sn-1 and an unsaturated fatty acyl chain (18:1 or 18:2) on the sn-2 position. Able to transfer phosphatidylcholine (PC) and phosphatidyetanolamline (PE) between membranes (By similarity). May play metabolic roles in sperm maturation or fertilization.|||Phosphorylation at Ser-284 by CK2 negatively regulates lipid transfer activity, possibly by decreasing membrane association.|||Testis, kidney, liver, and intestine with the highest level in the testis.|||flagellum http://togogenome.org/gene/10090:Elfn2 ^@ http://purl.uniprot.org/uniprot/Q68FM6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.|||Interacts with PPP1CA.|||Membrane http://togogenome.org/gene/10090:F9 ^@ http://purl.uniprot.org/uniprot/P16294 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by factor XIa, which excises the activation peptide. The propeptide can also be removed by snake venom protease.|||Belongs to the peptidase S1 family.|||Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain. Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein.|||Detected in liver.|||Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.|||Heterodimer of a light chain and a heavy chain; disulfide-linked. Interacts with SERPINC1.|||Predominantly O-glucosylated at Ser-99 by POGLUT1 in vitro.|||Secreted|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Usp53 ^@ http://purl.uniprot.org/uniprot/P15975 ^@ Caution|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although the active site residues are conserved, lacks the conserved His residue which is normally found 9 residues before the catalytic His.|||Belongs to the peptidase C19 family.|||Chimeric cDNA.|||Expressed in the cochlea. Isoform 1 expression levels are 10-fold higher than isoform 2 expression levels. Expressed in the liver.|||Interacts (via the C-terminal region) with the heterodimer TJP1:TJP2.|||Tight junction-associated protein that is involved in the survival of auditory hair cells and hearing. Maybe by modulating the barrier properties and mechanical stability of tight junctions (PubMed:26609154). Has no peptidase activity (PubMed:26609154).|||tight junction http://togogenome.org/gene/10090:Ccdc174 ^@ http://purl.uniprot.org/uniprot/Q3U155 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Probably involved in neuronal development. http://togogenome.org/gene/10090:Pcdha7 ^@ http://purl.uniprot.org/uniprot/Q91Y13 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane. Each cadherin domain binds three calcium ions (PubMed:27161523).|||Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination (PubMed:27161523). Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain (PubMed:27161523).|||Cell membrane|||Forms homodimers in trans (molecules expressed by two different cells) (PubMed:27161523). Forms promiscuous heterodimers in cis (at the plasma membrane of the same cell) with other protocadherins (PubMed:27161523). http://togogenome.org/gene/10090:Rab20 ^@ http://purl.uniprot.org/uniprot/P35295 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Golgi apparatus|||Plays a role in apical endocytosis/recycling. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and Mycobacterium. Plays a role in the fusion of phagosomes with lysosomes (By similarity).|||Present in a variety of tissues, but not in brain.|||phagosome|||phagosome membrane http://togogenome.org/gene/10090:Skint7 ^@ http://purl.uniprot.org/uniprot/A7XV04 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin, thymus, testis and, to a lower extent, bladder.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Ap1b1 ^@ http://purl.uniprot.org/uniprot/O35643|||http://purl.uniprot.org/uniprot/Q8CC13 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).|||Belongs to the adaptor complexes large subunit family.|||Golgi apparatus|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.|||Widely expressed.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Tprg ^@ http://purl.uniprot.org/uniprot/Q8CB49 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TPRG1 family.|||Cytoplasm|||Detected from embryonic stage 15.5 onwards. At stage 17.5 dpc, detected in epidermis and developing hair follicles. Expression levels in skin increase 4 days after birth and are mainly restricted to differentiated layers of the epidermis.|||Highly expressed in skin. Also detected at low levels in tongue and esophagus. http://togogenome.org/gene/10090:Gm6358 ^@ http://purl.uniprot.org/uniprot/D3YWL8 ^@ Function|||Subunit ^@ In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Lima1 ^@ http://purl.uniprot.org/uniprot/Q9ERG0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein involved in actin cytoskeleton regulation and dynamics. Increases the number and size of actin stress fibers and inhibits membrane ruffling. Inhibits actin filament depolymerization. Bundles actin filaments, delays filament nucleation and reduces formation of branched filaments (By similarity). Plays a role in cholesterol homeostasis. Influences plasma cholesterol levels through regulation of intestinal cholesterol absorption. May act as a scaffold protein by regulating NPC1L1 transportation, an essential protein for cholesterol absorption, to the plasma membrane by recruiting MYO5B to NPC1L1, and thus facilitates cholesterol uptake (PubMed:29880681).|||Cell membrane|||Contains at least 2 actin-binding domains, one on each side of the LIM domain. Both domains bind actin monomers and filaments. The C-terminal domain binds filaments more efficiently than the N-terminus (By similarity).|||Cytoplasm|||Deficient mice display reduced dietary cholesterol absorption.|||Highly expressed in the small intestine, including the duodenum, jejunum, and ileum. Low expression in the liver and very low expressed in the heart, spleen, lung, brain, and pancreas (PubMed:29880681). Isoform Alpha is highly expressed in embryos from day 7-11 and in adult spleen and lung. Isoform Beta expression is highest in adult kidney, testis, lung and liver, intermediate in heart, brain, spleen, skeletal muscle and low in embryos.|||Interacts with NPC1L1; bridges NPC1L1 with MYO5B (PubMed:29880681). Interacts with MYO5B; bridges MYO5B with NPC1L1 (PubMed:29880681). Interacts with PXN; this complex stabilizes actin dynamics (By similarity). Binds to G-actin and F-actin (PubMed:17875928) (By similarity).|||Phosphorylation of the C-terminal region by MAPK1/MAPK3 reduces its association with F-actin and contributes to actin filament reorganization and enhances cell motility.|||cytoskeleton|||ruffle|||stress fiber http://togogenome.org/gene/10090:Zfp750 ^@ http://purl.uniprot.org/uniprot/Q8BH05 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Transcription factor involved in epidermis differentiation. Required for terminal epidermal differentiation: acts downstream of p63/TP63 and activates expression of late epidermal differentiation genes. Specifically binds to the promoter of KLF4 and promotes its expression (By similarity). http://togogenome.org/gene/10090:Cox7b2 ^@ http://purl.uniprot.org/uniprot/Q9D2H1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome c oxidase VIIb family.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cbr3 ^@ http://purl.uniprot.org/uniprot/Q8K354 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the NADPH-dependent reduction of carbonyl compounds to their corresponding alcohols. Has low NADPH-dependent oxidoreductase activity. Acts on several orthoquinones, acts as well on non-quinone compounds, such as isatin or on the anticancer drug oracin. Best substrates for CBR3 is 1,2- naphthoquinone, hence could play a role in protection against cytotoxicity of exogenous quinones. Exerts activity toward ortho-quinones but not paraquinones. No endogenous substrate for CBR3 except isatin has been identified.|||Cytoplasm http://togogenome.org/gene/10090:Letm2 ^@ http://purl.uniprot.org/uniprot/Q7TNU7 ^@ Caution|||Subcellular Location Annotation ^@ Despite its name, it does not contain any EF-hand domains.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Meaf6 ^@ http://purl.uniprot.org/uniprot/Q2VPQ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EAF6 family.|||Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5 and the subunits EP400, TRRAP, BRD8, EPC1, DMAP1, RUVBL1, RUVBL2, ING3, actin, ACTL6A, MORF4L1, MORF4L2, MRGBP, YEATS4, VPS72 and MEAF6. Component of the HBO1 complex composed of KAT7/HBO1, MEAF6, ING4 or ING5, and one scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE scaffold (JADE1, JADE2 and JADE3) mediate acetylation of histone H4. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3.|||Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.|||kinetochore|||nucleolus http://togogenome.org/gene/10090:Trim8 ^@ http://purl.uniprot.org/uniprot/Q99PJ2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ At 10.5 and 12.5 dpc, expressed in the central nervous system. At 14.5 dpc, expressed in the eye (lens and inner neural layer of the retina), in the primitive glomeruli of the developing kidney, in the villi of the gut and in the dorsal root ganglia.|||Belongs to the TRIM/RBCC family.|||E3 ubiquitin-protein ligase that participates in multiple biological processes including cell survival, differentiation, apoptosis, and in particular, the innate immune response (PubMed:28747347, PubMed:31360105). Participates in the activation of interferon-gamma signaling by promoting proteasomal degradation of the repressor SOCS1 (PubMed:12163497). Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the 'Lys-63'-linked polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B (By similarity). Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus (By similarity). Negatively regulates TLR3/4-mediated innate immune response by catalyzing 'Lys-6'- and 'Lys-33'-linked polyubiquitination of TICAM1 and thereby disrupting the TICAM1-TBK1 interaction (PubMed:28747347).|||High expression in heart, liver, and thymus. Expressed in embryonic CNS, kidney, lens and gut.|||Homodimer. Interacts with SOCS1 (via) SH2 domain and SOCS box. Interacts with HSP90AB1; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1 (PubMed:21689689). Interacts with MAP3K7/TAK1 (By similarity). Interacts with PIAS3 (By similarity). Interacts with TICAM1 (PubMed:28747347). Interacts with TRIM15; this interaction prevents TRIM8 cytoplasmic translocation (By similarity).|||Mice are more susceptible to LPS and bacterial-induced death (PubMed:28747347). In addition, TRIM8 deletion plays a protective role in hepatocyte injury triggered by hepatic ischaemia/reperfusion (I/R) injury (PubMed:31360105).|||The coiled coil domain is required for homodimerization.|||The region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1. http://togogenome.org/gene/10090:Ap2a2 ^@ http://purl.uniprot.org/uniprot/P17427|||http://purl.uniprot.org/uniprot/Q69ZW4|||http://purl.uniprot.org/uniprot/Q6PEE6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1) (PubMed:19140243). Binds EPN1, EPS15, AMPH, SNAP91 and BIN1 (PubMed:10380931, PubMed:10430869, PubMed:12057195). Interacts with clathrin (PubMed:10459011). Interacts with HIP1 (By similarity). Interacts with DGKD (PubMed:17880279). Interacts with DENND1A, DENND1B and DENND1C (PubMed:20154091). Interacts with FCHO1 and DAB2 (PubMed:11247302, PubMed:22484487). Interacts with ATAT1; this interaction is required for efficient alpha-tubulin acetylation by ATAT1 (PubMed:24097348). Interacts with KIAA1107 (PubMed:29262337). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts with CLN3 (via dileucine motif) (By similarity). Interacts with ABCB11; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (By similarity).|||Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1).|||Belongs to the adaptor complexes large subunit family.|||Cell membrane|||Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif.|||Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif.|||Expressed in the brain (at protein level).|||coated pit http://togogenome.org/gene/10090:Dlx1 ^@ http://purl.uniprot.org/uniprot/Q64317 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the distal-less homeobox family.|||Expressed in a restricted region of the developing brain, within the diencephalon and the adjacent telencephalic regions.|||Expressed in developing retinal progenitor cells at 12 dpc (PubMed:21875655). Has a segmental expression in the developing forebrain (PubMed:1676488).|||Interacts with SMAD4 (via homeobox DNA-binding domain) (By similarity). Interacts (via homeobox DNA-binding domain) with POU4F2; this interaction suppresses DLX1-mediated transcriptional activity in postnatal retina and enhances retinal ganglion cell (RGC) differentiation (PubMed:21875655).|||Nucleus|||Plays a role as a transcriptional activator or repressor (PubMed:21875655). Inhibits several cytokine signaling pathways, such as TGFB1, activin-A/INHBA and BMP4 by interfering with the transcriptional stimulatory activity of transcription factors, such as MSX2, FAST2, SMAD2 and SMAD3 during hematopoietic cell differentiation (By similarity). Plays a role in terminal differentiation of interneurons, such as amacrine and bipolar cells in the developing retina (PubMed:21875655). Likely to play a regulatory role in the development of the ventral forebrain (PubMed:1676488). May play a role in craniofacial patterning and morphogenesis and may be involved in the early development of diencephalic subdivisions (PubMed:1676488).|||The homeobox DNA-binding domain is necessary for its nuclear localization, transcriptional and erythroid differentiation activities. http://togogenome.org/gene/10090:ccdc198 ^@ http://purl.uniprot.org/uniprot/Q9CPZ1 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Cytoplasmic vesicle|||Deficient mice are viable without major developmental, morphological or behavioral defects. However, body weight and mean lean body mass are significantly altered in knockout mice. Mice display significant decrease in serum ferritin and high amount of albumin in the urine. Pregnant knockout females subjected to iron deficit diet, result in developing embryos with altered sizes of inner organs and interscapular brown adipose tissue.|||Expressed in proximal tubules of the kidney.|||May be involved in tuning the metabolism, energy expenditure, and excretion processes. http://togogenome.org/gene/10090:Thy1 ^@ http://purl.uniprot.org/uniprot/P01831 ^@ Function|||Polymorphism|||Subcellular Location Annotation ^@ Cell membrane|||May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain.|||There are two major alleles; Thy-1.1 (CD90.1) and Thy-1.2 (CD90.2). http://togogenome.org/gene/10090:Ssbp4 ^@ http://purl.uniprot.org/uniprot/Q3U4B1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Nab2 ^@ http://purl.uniprot.org/uniprot/Q3TYF1|||http://purl.uniprot.org/uniprot/Q61127 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2. Isoform 2 lacks repression ability.|||Belongs to the NAB family.|||By serum stimulation.|||Highly expressed in brain and thymus, and at lower levels in spleen, kidney, heart and testis. Isoform 1 is predominantly expressed in testis, whereas isoform 3 is more abundant in thymus.|||Homomultimers may associate with EGR1 bound to DNA.|||Nucleus|||Sumoylation by EGR2 represses EGR2 transcriptional activity in hindbrain.|||The NAB conserved domain 1 (NCD1) interacts with EGR1 inhibitory domain and mediates multimerization.|||The NAB conserved domain 2 (NCD2) is necessary for transcriptional repression. http://togogenome.org/gene/10090:Kif19a ^@ http://purl.uniprot.org/uniprot/A9XMT8|||http://purl.uniprot.org/uniprot/Q99PT9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Mice show growth retardation, higher mortality (4 weeks after birth) and display hydrocephalus as well as female infertility. Female infertility is probably caused by fallopian tube obstruction. Phenotypes are due to abnormally elongated cilia that cannot generate proper fluid flow.|||Plus end-directed microtubule-dependent motor protein that regulates the length of motile cilia by mediating depolymerization of microtubules at ciliary tips.|||Strongly expressed in the oviduct and trachea. Expressed in testis, lung, ovary and brain.|||cilium|||cytoskeleton http://togogenome.org/gene/10090:Phf1 ^@ http://purl.uniprot.org/uniprot/A0A494BBE6|||http://purl.uniprot.org/uniprot/Q9Z1B8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated component of the PRC2 complex. Interacts with p53/TP53 (By similarity). Interacts with CHMP1.|||Belongs to the Polycomblike family.|||Nucleus|||Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Involved in DNA damage response and is recruited at double-strand breaks (DSBs). Acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting the PRC2 complex: it is however unclear whether recruitment of the PRC2 complex to H3K36me3 leads to enhance or inhibit H3K27me3 methylation mediated by the PRC2 complex. According to some reports, PRC2 recruitment by PHF1 promotes H3K27me3 and subsequent gene silencing by inducing spreading of PRC2 and H3K27me3 into H3K36me3 loci (PubMed:18086877). According to other reports, PHF1 recruits the PRC2 complex at double-strand breaks (DSBs) and inhibits the activity of PRC2. Regulates p53/TP53 stability and prolonges its turnover: may act by specifically binding to a methylated from of p53/TP53.|||Testis-specific.|||The Tudor domain recognizes and binds H3K36me3.|||centrosome http://togogenome.org/gene/10090:Gm7735 ^@ http://purl.uniprot.org/uniprot/D3YX18 ^@ Function|||Subunit ^@ In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Fbxo40 ^@ http://purl.uniprot.org/uniprot/P62932 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Directly interacts with SKP1 and CUL1.|||During the development of skeletal muscle, can only be detected 2 weeks after birth.|||Expressed only in heart and skeletal muscle.|||Probable substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that may function in myogenesis. http://togogenome.org/gene/10090:Cmtm2b ^@ http://purl.uniprot.org/uniprot/Q9DAC0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chemokine-like factor family.|||Membrane http://togogenome.org/gene/10090:Npy4r ^@ http://purl.uniprot.org/uniprot/Q61041 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||G protein-coupled receptor for PPY/pancreatic polypeptide/PP that is negatively coupled to cAMP (PubMed:8641440). Has much lower affinity for the NPY/neuropeptide Y and PYY/peptide YY (PubMed:8641440).|||Heart, detected in small intestine. http://togogenome.org/gene/10090:C9orf72 ^@ http://purl.uniprot.org/uniprot/Q6DFW0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27193190, PubMed:27617292). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (By similarity). The C9orf72-SMCR8 complex also acts as a regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and modulating its protein kinase activity (PubMed:27193190, PubMed:27617292). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (By similarity). Positively regulates initiation of autophagy by regulating the RAB1A-dependent trafficking of the ULK1/ATG1 kinase complex to the phagophore which leads to autophagosome formation (By similarity). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27875531). Plays a role in endosomal trafficking (PubMed:26989253). May be involved in regulating the maturation of phagosomes to lysosomes (PubMed:26989253). Promotes the lysosomal localization and lysosome-mediated degradation of CARM1 which leads to inhibition of starvation-induced lipid metabolism (PubMed:30366907). Regulates actin dynamics in motor neurons by inhibiting the GTP-binding activity of ARF6, leading to ARF6 inactivation (PubMed:27723745). This reduces the activity of the LIMK1 and LIMK2 kinases which are responsible for phosphorylation and inactivation of CFL1/cofilin, leading to cofilin activation (PubMed:27723745). Positively regulates axon extension and axon growth cone size in spinal motor neurons (PubMed:27723745). Required for SMCR8 protein expression and localization at pre- and post-synaptic compartments in the forebrain, also regulates protein abundance of RAB3A and GRIA1/GLUR1 in post-synaptic compartments in the forebrain and hippocampus (PubMed:31651360). Plays a role within the hematopoietic system in restricting inflammation and the development of autoimmunity (PubMed:27412785).|||Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (Probable). The complex is formed of two protomers, each individually consisting of one molecule each of C9orf72, SMCR8 and WDR41 (By similarity). The protomers homodimerize via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-terminus) (By similarity). Within each protomer SMCR8 (via DENN domain) acts as a bridging protein between WDR41 (via C-terminus and N-terminus) and C9orf72 (via C-terminus) (By similarity). The C9orf72-SMCR8 complex associates with the ULK1/ATG1 kinase complex (By similarity). Interacts with ULK1/ATG1 kinase complex members ULK1, ATG13 and RB1CC1 (By similarity). Interacts with SMCR8; the interaction is direct (PubMed:27875531). Interacts with HNRNPA1, HNRNPA2B1 and UBQLN2 (By similarity). Interacts with small Rab GTPase RAB1A; the interaction mediates recruitment of RAB1A to the ULK1/ATG1 kinase complex (PubMed:24549040). Also interacts with small Rab GTPase RAB7A (PubMed:24549040). Interacts with cofilin (PubMed:27723745). Interacts with GTP-binding proteins ARF1 and ARF6 (PubMed:27723745). Interacts with the DLG4/PSD-95 (PubMed:31651360). Interacts with CARM1 (via PH domain-like fold) (PubMed:30366907).|||Cytoplasm|||Decreased life span (PubMed:27875531, PubMed:27412785). However, another report did not observe any effect on life span (PubMed:26989253). Lymph node and spleen enlargement phenotype accompanied by macrophage infiltration (PubMed:27193190, PubMed:27875531, PubMed:26989253, PubMed:27412785). Severe inflammation also observed in liver (PubMed:27193190, PubMed:27412785). Increased total white blood cell count due to a significant increase in the number of circulating neutrophils (PubMed:27412785). Significantly reduced platelet and red blood cell count (PubMed:27412785). Increased levels of autophagy and lysosomal proteins and autophagy defects in the spleen and liver (PubMed:27193190). Impaired activation of MTOR/mTOR (PubMed:27875531). Massive up-regulation of the cell surface receptor Trem2 (PubMed:26989253). Significantly increased levels of a number of inflammatory chemokines and cytokines (PubMed:26989253, PubMed:27412785). Increased levels of autoantibodies indicative of an autoimmune phenotype (PubMed:27412785). Normal weight gain, sensorimotor coordination, limb strength, femoral motor and sensory axon counts, and muscle electrophysiology (PubMed:26989253). Conditional knockout in neurons and glial cells results in significantly reduced body weight but does not induce motor neuron degeneration, defects in motor function or altered survival (PubMed:26044557). SMCR8 protein expression is abolished in pre- and post-synaptic compartments in forebrain synapses (PubMed:31651360). RAB3A expression levels are increased in synaptosomes, however are decreased in post-synaptic compartments of the forebrain and in the hippocampus (PubMed:31651360). GRIA1/GLUR1 protein levels are increased in forebrain post-synaptic compartments and in the hippocampus (PubMed:31651360).|||Endosome|||Expressed in cerebral cortex and hippocampus at embryonic day 18 and postnatal days 1, 7, 14, 28 and 56.|||Expressed in postnatal cerebellum and cortex (at protein level). Neuronal expression is detected in several regions of the adult brain and spinal cord (PubMed:26044557). Prominent expression also observed in embryonic and early postnatal neurons including retinal ganglion cells, sensory neurons in the olfactory epithelium and in dorsal root ganglia, and spinal motor neurons (PubMed:26044557). Expressed in the developing cerebral cortex, cerebellum, olfactory bulb, hippocampus and spinal cord in the embryo and in P0 cortical neurons and astrocytes (PubMed:27476503). Also expressed in non-neuronal tissues such as kidney and tooth (PubMed:26044557). In the spleen, highly expressed in myeloid cells compared to B cell and T cell populations where expression is much lower (PubMed:26989253). In the brain, highly expressed in microglia (PubMed:26989253).|||Expressed in the forebrain, including in the glomerular layer of the olfactory bulb (at protein level).|||Lysosome|||Nucleus|||P-body|||Perikaryon|||Postsynapse|||Presynapse|||Secreted|||Stress granule|||autophagosome|||axon|||dendrite|||growth cone http://togogenome.org/gene/10090:Ociad2 ^@ http://purl.uniprot.org/uniprot/Q9D8W7 ^@ Subcellular Location Annotation ^@ Endosome http://togogenome.org/gene/10090:Vmn1r238 ^@ http://purl.uniprot.org/uniprot/E9Q373 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Adgrf3 ^@ http://purl.uniprot.org/uniprot/Q58Y75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Expression is restricted to testis and circumvallate papillae.|||Membrane|||Orphan receptor. http://togogenome.org/gene/10090:Ccnd2 ^@ http://purl.uniprot.org/uniprot/P30280|||http://purl.uniprot.org/uniprot/Q4FK45 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin D subfamily.|||Cytoplasm|||Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex.|||Nucleus|||Nucleus membrane|||Phosphorylation at Thr-280 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.|||Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals.|||Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-280 phosphorylation (PubMed:33854232, PubMed:33854235). The DCX(AMBRA1) complex represents the major regulator of CCND2 stability during the G1/S transition (PubMed:33854232, PubMed:33854235). Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Slc16a2 ^@ http://purl.uniprot.org/uniprot/O70324|||http://purl.uniprot.org/uniprot/Q05BA2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Deficient mice display abnormal thyroid hormone metabolism with no apparent neurological phenotype.|||Expressed in cerebral microvessels.|||Membrane|||Monomer (By similarity). Homodimer (By similarity). Homooligomer (By similarity).|||Specific thyroid hormone transmembrane transporter, that mediates both uptake and efflux of thyroid hormones across the cell membrane independently of pH or a Na(+) gradient (PubMed:31436139). Major substrates are the iodothyronines T3 and T4 and to a lesser extent rT3 and 3,3-diiodothyronine (3,3'-T2). Acts as an important mediator of thyroid hormone transport, especially T3, through the blood-brain barrier (PubMed:19147674).|||Strong expression in the brain barriers and many subpopulations of neurons, including cortical and cerebellar neurons at postnatal day 6. Decrease expression in neurons upon aging, whereas expression in the blood-brain barrier and blood-cerebrospinal fluid barrier do not change upon aging (at protein level). http://togogenome.org/gene/10090:Ippk ^@ http://purl.uniprot.org/uniprot/A0A217FL54|||http://purl.uniprot.org/uniprot/Q6P1C1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the IPK1 type 2 family.|||Cytoplasm|||Death during ermbryogenesis before 8.5 dpc, suggesting that InsP6 is required for yolk sac function and development.|||In 9 dpc embryos it is expressed in regions corresponding to the neural tube, notochord and somites. Through the neural tube, it is expressed in the ventricular zone and in migrating neuroblasts. Also expressed in the notochord and specific regions of the somite. Strongly expressed in the myotome (future skeletal muscle) of the somite. In addition to the neural tube, it is also expressed in the ventricular zone and migrating neuroblasts throughout the embryonic brain. Prominent expression is detected in the yolk sac and embryonic heart. Within the yolk sac, it is expressed in both the epithelial and endothelial layers (blood vessels) but absent from the blood islands. In the heart, it is detected in both the atrial and ventricular chambers. In the ventricular myocardium it is present in both the endocardium and myocardium. Also expressed in the cardinal vein, aorta, digestive tract, and pharyngeal arches.|||In brain, it is expressed throughout the hippocampus (CA1, CA2, CA3 and dentate gyrus), inner layers of the cerebral cortex, and Purkinje cells of the cerebellum. In heart, it is expressed in cardiomyocytes but not in interstitial cells, blood vessels, or valves. Also expressed in testis.|||Nucleus|||Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate).|||Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, non-homologous end-joining, endocytosis, ion channel regulation. It also protects cells from TNF-alpha-induced apoptosis.|||The EXKPK motif is conserved in inositol-pentakisphosphate 2-kinases of both family 1 and 2. http://togogenome.org/gene/10090:Trpc6 ^@ http://purl.uniprot.org/uniprot/Q3UZG1|||http://purl.uniprot.org/uniprot/Q61143|||http://purl.uniprot.org/uniprot/Q6NV56 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC6 sub-subfamily.|||Cell membrane|||Homodimer; forms channel complex. Interacts with MX1 and RNF24.|||Lung and brain.|||Membrane|||N-glycosylated.|||Phosphorylated by FYN, leading to an increase of TRPC6 channel activity.|||Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C. Seems not to be activated by intracellular calcium store depletion. http://togogenome.org/gene/10090:Copg1 ^@ http://purl.uniprot.org/uniprot/Q9QZE5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COPG family.|||COPI-coated vesicle membrane|||Golgi apparatus membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits. Interacts with ZNF289/ARFGAP2 through its C-terminal appendage domain (By similarity). Interacts with EGFR upon EGF treatment; interaction is essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER (By similarity). Interacts with COPB1 (By similarity). Interacts with TMED10 (via C-terminus). Interacts with TMED2, TMED3, TMED7 and TMED9 (By similarity).|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte triglyceride lipase (PNPLA2) with the lipid droplet surface to mediate lipolysis.|||cytosol http://togogenome.org/gene/10090:Slc40a1 ^@ http://purl.uniprot.org/uniprot/Q9JHI9 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.|||Cell membrane|||Deficient mice exhibit embryonic lethality. These mice cannot transfer iron from the extraembryonic visceral endoderm into the embryo proper, leading to a defect in embryonic growth and consequent death (PubMed:16054062). Erythroid-specific deletion reduces serum iron but increased tissue iron contents (PubMed:30213870).|||During elevated serum iron levels, liver-derived hepcidin/HAMP negatively regulates cell surface ferroportin/SLC40A1 by inducing its ubiquitination, internalization, and degradation. Indeed, hepcidin/HAMP affinity towards ferroportin/SLC40A1 increases by 80-fold in the presence of iron.|||High expression in spleen, liver, kidney, heart and duodenum.|||Identified in a complex with STOM. Interacts with HAMP; this interaction promotes SLC40A1 rapid ubiquitination.|||Manganese (Mn) transport by SLC40A1 remains controversial. Some in vitro studies have suggested that SLC40A1 transports minimal amounts of Mn(2+) (By similarity). Other groups have suggested that it does not (By similarity). The predicted apparent affinity of SLC40A1 for manganese is extremely low compared with iron, implying that any SLC40A1-mediated Mn transport in vivo would likely be trivial (By similarity). A recent study examined the role of SLC40A1 in Mn homeostasis by using Tmprss6-O mice, which express high levels of hepcidin/HAMP and therefore have very low SLC40A1 levels in their tissues. These mice show frank iron deficiency and reduced iron levels in most tissues, but manganese levels are largely unaffected (PubMed:30888356). These studies suggest that manganese is propably not the physiological substrate of SLC40A1.|||Polyubiquitinated by RNF217; leading to proteasomal degradation (PubMed:33895792). Ubiquitination is necessary for its internalization by hepcidin/HAMP (By similarity).|||Transports Fe(2+) from the inside of a cell to the outside of the cell, playing a key role for maintaining systemic iron homeostasis (PubMed:16054062, PubMed:30213870). Transports iron from intestinal, splenic, hepatic cells, macrophages and erythrocytes into the blood to provide iron to other tissues. Controls therefore dietary iron uptake, iron recycling by macrophages and erythrocytes, and release of iron stores in hepatocytes (PubMed:16054062, PubMed:30213870). When iron is in excess in serum, circulating HAMP/hepcidin levels increase resulting in a degradation of SLC40A1, thus limiting the iron efflux to plasma (By similarity). http://togogenome.org/gene/10090:Nfia ^@ http://purl.uniprot.org/uniprot/B1AUC0|||http://purl.uniprot.org/uniprot/Q02780|||http://purl.uniprot.org/uniprot/Q05B39|||http://purl.uniprot.org/uniprot/Q3UTK6 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CTF/NF-I family.|||Binds DNA as a homodimer.|||Incomplete sequence.|||Nucleus|||Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Ndufa5 ^@ http://purl.uniprot.org/uniprot/D3YTQ8|||http://purl.uniprot.org/uniprot/Q9CPP6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Acetylation of Lys-98 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the complex I NDUFA5 subunit family.|||Complex I is composed of 45 different subunits.|||Lethality around embryonic day 9 (E9). Conditional knockout in the central nervous system does not lead to any visible phenotype until mice reach 10-11 months of age: then mice become lethargic, lose motor control and have difficulty maintaining balance. Defects cause loss of other complex I subunits and reduced NADH dehydrogenase activity.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Tmem94 ^@ http://purl.uniprot.org/uniprot/A0A668KL57|||http://purl.uniprot.org/uniprot/Q7TSH8 ^@ Disruption Phenotype|||Subcellular Location Annotation ^@ Deficient mice are embryonic lethal and exhibit craniofacial defects, cardiac abnormalities, and abnormal neuronal migration in the central nervous system.|||Membrane http://togogenome.org/gene/10090:Uqcrq ^@ http://purl.uniprot.org/uniprot/Q9CQ69 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UQCRQ/QCR8 family.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783). Interacts with UQCC6 (PubMed:32161263).|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lsg1 ^@ http://purl.uniprot.org/uniprot/Q3UM18 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class YlqF/YawG GTPase family. LSG1 subfamily.|||Cytoplasm|||Endoplasmic reticulum|||GTPase required for the XPO1/CRM1-mediated nuclear export of the 60S ribosomal subunit. Probably acts by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm (By similarity).|||In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.|||Nucleus http://togogenome.org/gene/10090:Serp1 ^@ http://purl.uniprot.org/uniprot/Q9Z1W5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAMP4 family.|||Endoplasmic reticulum membrane|||Interacts with SEC61B, SEC61A1 and the SEC61 complex. Interacts with CANX (By similarity).|||Interacts with target proteins during their translocation into the lumen of the endoplasmic reticulum. Protects unfolded target proteins against degradation during ER stress. May facilitate glycosylation of target proteins after termination of ER stress. May modulate the use of N-glycosylation sites on target proteins (By similarity).|||Membrane http://togogenome.org/gene/10090:Gins2 ^@ http://purl.uniprot.org/uniprot/Q9D600 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GINS2/PSF2 family.|||Chromosome|||Component of the GINS complex which is a heterotetramer of GINS1, GINS2, GINS3 and GINS4. Forms a stable subcomplex with GINS3. GINS complex interacts with DNA primase in vitro. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex.|||Nucleus|||Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. http://togogenome.org/gene/10090:Camk4 ^@ http://purl.uniprot.org/uniprot/Q8BGR3 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Lsmem1 ^@ http://purl.uniprot.org/uniprot/Q3UQS2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Trmt11 ^@ http://purl.uniprot.org/uniprot/E9QKG3 ^@ Function|||Subunit ^@ Catalytic subunit of an S-adenosyl-L-methionine-dependent tRNA methyltransferase complex that mediates the methylation of the guanosine nucleotide at position 10 (m2G10) in tRNAs.|||Interacts with TRMT112. http://togogenome.org/gene/10090:Rtraf ^@ http://purl.uniprot.org/uniprot/Q4VA29|||http://purl.uniprot.org/uniprot/Q9CQE8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RTRAF family.|||Homodimer. Interacts with FAM98A (via N- and C-terminus). Interacts with NIN; which may prevent phosphorylation of NIN. Interacts with POLR2A. Component of a tRNA-splicing ligase complex.|||Nucleus|||RNA-binding protein involved in modulation of mRNA transcription by Polymerase II. Component of the tRNA-splicing ligase complex and is required for tRNA ligation. May be required for RNA transport.|||centrosome|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Zfp112 ^@ http://purl.uniprot.org/uniprot/Q0VAW7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Cic ^@ http://purl.uniprot.org/uniprot/Q924A2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the cortex and hypothalamus (at protein level). Isoform 1: Present in cerebellum (at protein level) (PubMed:17190598). Isoform 2: Present in cerebellum (at protein level) (PubMed:17190598).|||Expressed postnatally in the hippocampus, neocortex, olfactory bulb and cerebellum. Expressed in the hippocampus from P0 to P15. Expressed in the posterior region of the neocortex at P4, the anterior region at P9, and is then lost by P15. Expressed in the cerebellum from P0, specifically within the external granule layer (EGL) which contains granule cell precursors. By P7 expression is distributed throughout the EGL and is reduced in the inner granule cell layer (IGL) where granule cells finally differentiate. Expression in the IGL continues to diminish up to P15, when granule cell neurogenesis is complete.|||Intron retention.|||Isoform 1: Interacts with ATXN1 (PubMed:17190598). Isoform 2: Interacts with ATXN1 (PubMed:17190598). Interacts with ATXN1L (PubMed:17322884). Found in a complex with ATXN1 and ATXN1L (PubMed:28288114).|||Mice with conditional knockouts of either ATXN1-ATXN1L or CIC in the developing forebrain exhibit intellectual disability, hyperactivity, social-behavioral deficits and reduced thickness of upper cortical layers.|||Nucleus|||Transcriptional repressor which plays a role in development of the central nervous system (CNS) (PubMed:17190598). In concert with ATXN1 and ATXN1L, involved in brain development (PubMed:28288114). http://togogenome.org/gene/10090:Fam89a ^@ http://purl.uniprot.org/uniprot/Q14BJ1 ^@ Similarity ^@ Belongs to the FAM89 family. http://togogenome.org/gene/10090:Ccl20 ^@ http://purl.uniprot.org/uniprot/O89093|||http://purl.uniprot.org/uniprot/Q54AI7|||http://purl.uniprot.org/uniprot/Q642U4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a ligand for C-C chemokine receptor CCR6. Signals through binding and activation of CCR6 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:9862452, PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and autoimmune diseases (PubMed:21376174). CCL20 acts as a chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes (By similarity). Involved in the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation (PubMed:19050256). Required for optimal migration of thymic natural regulatory T cells (nTregs) and DN1 early thymocyte progenitor cells (PubMed:24638065). Positively regulates sperm motility and chemotaxis via its binding to CCR6 which triggers Ca2+ mobilization in the sperm which is important for its motility (PubMed:25122636). May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells (PubMed:10064080).|||Belongs to the intercrine beta (chemokine CC) family.|||By lipopolysaccharide (LPS), TNF-alpha and interleukin-1. IFN-gamma alone showed no effect, but potentiated the effect of TNF. Induced synergistically by TGFB1 and IL6, which requires STAT3, RORC and IL21.|||Secreted|||Thymic medulla (at protein level). Prominently expressed in the small intestine, colon and appendix. Also found in thymus, spleen, lymph node and lung. The long form might be dominant in intestinal, and the short form in lymphoid tissues. Expressed by IL17 producing helper T-cells (Th17). http://togogenome.org/gene/10090:Mpi ^@ http://purl.uniprot.org/uniprot/Q3V100|||http://purl.uniprot.org/uniprot/Q924M7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mannose-6-phosphate isomerase type 1 family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. http://togogenome.org/gene/10090:Zfpm2 ^@ http://purl.uniprot.org/uniprot/Q8CCH7 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FOG (Friend of GATA) family.|||Expressed in heart, brain and testis. Weakly expressed in lung and liver. First expressed at approximately E8.5 in the developing ventral heart tube and septum transversum. Cardiac expression persists throughout the remainder of embryonic development in the atria as well as in all layers of the ventricles (endocardium, myocardium, and pericardium). Expressed in the neuroepithelium of the developing midbrain and hindbrain from 11.5 dpc and increased in intensity between 12 dpc and 16.5 dpc. Also expressed in the urogenital ridge beginning at 11.5 dpc and subsequently localized to the gonads by 16.5 dpc. Colocalizes with GATA4 GATA5 and GATA6 in the developing heart, GATA3 in the brain, and GATA4 in the gonads.|||Interacts with the N-terminal zinc-finger of GATA4, GATA5 and probably GATA6. Interacts with retinoid nuclear receptor RXRA when ligand bound. Interacts with corepressor CTBP2; this interaction is however not essential for corepressor activity. Interacts with NR2F2 and NR2F6. Interacts with ATOH8; mediates indirect interaction with GATA4.|||Mice die of congestive heart failure at 13 dpc with a syndrome of tricuspid atresia that includes an absent tricuspid valve, a large atrial and ventricular spetal defects, an elongated left ventricular outflow tract, rightward displacement of the aortic valve and pulmonic stenosis. These mice also display hypoplasia of the compact zone of the left ventricle.|||Nucleus|||Splicing donor site between exon 3 and 4 is not canonical.|||Sumoylation reduces transcriptional repression activity.|||The CCHC FOG-type zinc fingers 1, 2, 3 and 5 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC FOG-type zinc finger is probably essential for the interaction with GATA-type zinc fingers.|||Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA4, GATA5 and GATA6. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. Also required in gonadal differentiation, possibly be regulating expression of SRY. Probably acts a corepressor of NR2F2. http://togogenome.org/gene/10090:Bcl9l ^@ http://purl.uniprot.org/uniprot/Q67FY2 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BCL9 family.|||Expressed in embryo.|||Expressed in kidney, liver, lung, testis, brain, spleen, heart and skeletal muscle. Highly expressed in numerous colorectal tumors compared to corresponding non-cancerous tissues.|||Found in a complex with CDC73; CTNNB1 and PYGO1 (By similarity). Interacts with CTNNB1.|||Nucleus|||Tne C-terminal domain is important for its transactivation activity.|||Transcriptional regulator that acts as an activator. Promotes beta-catenin transcriptional activity. Plays a role in tumorigenesis. Enhances the neoplastic transforming activity of CTNNB1. http://togogenome.org/gene/10090:Cbfa2t3 ^@ http://purl.uniprot.org/uniprot/B7ZP57|||http://purl.uniprot.org/uniprot/E9QM80|||http://purl.uniprot.org/uniprot/O54972 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CBFA2T family.|||Expressed during embryogenesis from 7 to 17 dpc.|||Golgi apparatus membrane|||Heterodimer with RUNX1T1 and CBFA2T2. Interacts with ZNF652 and ERBB4. May interact with PRKAR2A, PDE7A and probably PDE4A. Interacts with PLXNA1, PLXNA3 and PRKAR1A (By similarity). Interacts with HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, NCOR1 and NCOR2. Component of a TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3. Interacts with ZBTB4, ZBTB38 and ZBTB33. Interacts with HIF1A and EGLN1 (By similarity).|||Nervy homology region 2 (NHR2) mediates homo- and possibly heterotypic oligomerization by forming a four-helix bundle tetrameric structure.|||Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes. Can repress the expression of MMP7 in a ZBTB33-dependent manner. Reduces the protein levels and stability of the transcriptinal regulator HIF1A; interacts with EGLN1 and promotes the HIF1A prolyl hydroxylation-dependent ubiquitination and proteasomal degradation pathway. Contributes to inhibition of glycolysis and stimulation of mitochondrial respiration by down-regulating the expression of glycolytic genes including PFKFB3, PFKFB4, PDK1, PFKP, LDHA and HK1 which are direct targets of HIF1A (By similarity). Regulates the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes (PubMed:16407974). Plays a role in granulocyte differentiation (PubMed:15231665).|||Up-regulated during hematopoietic differentiation.|||Widely expressed with higher expression in heart, brain, lung and spleen. Expressed in hematopoietic cells (at protein level).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Prdm1 ^@ http://purl.uniprot.org/uniprot/Q60636 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Up-regulated in response to Herpes simplex virus (HSV) infection in skin and spleen memory CD8(+) T cells.|||(Microbial infection) Up-regulated in response to Lymphocytic choriomeningitis virus (LCMV) in memory CD8(+) T cells.|||Belongs to the class V-like SAM-binding methyltransferase superfamily.|||By lymphokines, specifically IL-2 and IL-5. Up-regulated during dendritic cell maturation.|||Cytoplasm|||Early embryonic lethality (PubMed:19737919). Compound heterozygotes display germ cell defects and a rudimentary or missing fifth digit of the forelimb (PubMed:19737919). Conditional knockout in lymphocyte T cells show a weak reduction in tissue-resident memory T (Trm) cell population maintenance in the skin, gut, liver and kidney but not of splenic T cells (PubMed:27102484). Double knockouts for PRDM1/BLIMP1 and ZNF683 result in a strong inhibition of Trm cell population maintenance but not of circulating memory cells (PubMed:27102484). Display an enhancement of natural killer T (NKT) cells migration preferentially to the white pulp of the spleen in response to chemotactic stimuli (PubMed:27102484).|||Expressed in bone marrow macrophages (at protein level) (PubMed:32741026). Expressed in innate lymphocytes, including tissue-resident conventional natural killer (cNK) cells in liver (PubMed:27102484). Expressed also weakly in tissue-resident natural killer (trNK) and natural killer T (NKT) cells in liver (PubMed:27102484).|||Expressed in bone marrow, spleen and lymph node but not in brain, heart, kidney, liver, ovary or muscle. Weak expression detected in the lung.|||Expressed in embryo, yolk sac, placenta, splenocytes, and activated T-cells.|||Expressed only in the yolk sac.|||Interacts with PRMT5 (PubMed:16699504). Interacts with FBXO10 (By similarity). Interacts with FBXO11 (By similarity). Interacts with multiple nuclear sumoylation E3 ligases, including CBX4, PIAS1, PIAS2, PIAS3, PIAS4, PML and RNF4, but not RANBP2 (By similarity). Interacts with LDB1, SMARCD3 and SMARCC1 (By similarity). Interacts with EEIG1; following TNFSF11/RANKL stimulation in bone marrow-derived macrophages, the interaction promotes the binding of PRDM1/BLIMP1 to the gene promoter of IRF8 (PubMed:32741026).|||Nucleus|||Produced by alternative promoter usage of isoform 2.|||Produced by alternative splicing of isoform 1.|||Produced by alternative splicing of isoform 1. Does not bind DNA.|||Produced by alternative splicing.|||Sumoylation at Lys-847 by PIAS1 increases transcriptional repressor activity, and is critical for plasma cell differentiation (By similarity). Can be sumoylated with SUMO1 and SUMO2 by PML. Degradation of the wild-type protein mostly depends upon sumoylation, rather than ubiquitination (By similarity). Desumoylated by SENP1 and SENP6 (By similarity).|||Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs (PubMed:27102484). Plays a role in the development, retention and long-term establishment of adaptive and innate tissue-resident lymphocyte T cell types in non-lymphoid organs, such as the skin and gut, but also in other nonbarrier tissues like liver and kidney, and therefore may provide immediate immunological protection against reactivating infections or viral reinfection (PubMed:27102484). Binds specifically to the PRDI element in the promoter of the beta-interferon gene (By similarity). Drives the maturation of B-lymphocytes into Ig secreting cells (By similarity). Associates with the transcriptional repressor ZNF683 to chromatin at gene promoter regions (PubMed:27102484). Binds to the promoter and acts as a transcriptional repressor of IRF8, thereby promotes transcription of osteoclast differentiation factors such as NFATC1 and EEIG1 (PubMed:32741026).|||Ubiquitinated by SCF(FBXO11), leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Tcf7l1 ^@ http://purl.uniprot.org/uniprot/A1A549|||http://purl.uniprot.org/uniprot/A1A550|||http://purl.uniprot.org/uniprot/Q9Z1J1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCF/LEF family.|||Binds the armadillo repeat of CTNNB1 and forms a stable complex (PubMed:9488439). Interacts with DAZAP2 (By similarity).|||Detected in the basal layer of epidermis and in outer root sheath and bulge of hair follicles.|||Nucleus|||Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis.|||The putative Groucho interaction domain between the N-terminal CTNNB1 binding domain and the HMG-box is necessary for repression of the transactivation mediated by TCF7L1 and CTNNB1. http://togogenome.org/gene/10090:Shox2 ^@ http://purl.uniprot.org/uniprot/A0A140T8S9|||http://purl.uniprot.org/uniprot/P70390 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Expressed from 9 dpc to 16 dpc in the heart, otic region, maxillary and mandibular components of the first branchial arch, nasal processes, eyelid, midbrain, medulla oblongata, limbs, dorsal root ganglia and genital tubercle. Also expressed in non-neuronal structures around the oral cavity and in hip and shoulder regions and in mesenchyme surrounding the vertebrae.|||Highly expressed in striated muscle followed by liver, kidney, testis, brain, heart, lung and spleen.|||May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation. May also have a role in heart development.|||Nucleus http://togogenome.org/gene/10090:Or5w13 ^@ http://purl.uniprot.org/uniprot/Q0VBI4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lhfpl2 ^@ http://purl.uniprot.org/uniprot/Q8BGA2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LHFP family.|||Expressed in the epithelium of the vas deferens (at protein level). Widely expressed (PubMed:26964900). Strongly expressed in heart, spleen, liver, kidney, thymus, testis, brain, lung, intestine, vagina, ovary and uterus (PubMed:26964900). Expressed in follicle cells of the ovary, epithelial cells of the oviduct, both luminal and glandular epithelial cells of the uterus, and epithelial cells of the vagina (PubMed:26964900).|||Membrane|||Plays a role in female and male fertility. Involved in distal reproductive tract development (PubMed:26964900). http://togogenome.org/gene/10090:Or10al3 ^@ http://purl.uniprot.org/uniprot/Q7TRJ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myl7 ^@ http://purl.uniprot.org/uniprot/Q9QVP4 ^@ Miscellaneous|||Subunit|||Tissue Specificity ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains.|||Predominantly expressed in adult atrial muscle.|||This chain binds calcium. http://togogenome.org/gene/10090:Map3k15 ^@ http://purl.uniprot.org/uniprot/A2AQW0 ^@ Activity Regulation|||Function|||Similarity ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Contains an N-terminal autoinhibitory domain. Activated by phosphorylation at Thr-816, inhibited by phosphorylation at Ser-928 (By similarity).|||Serine/threonine kinase which acts as a component of the MAP kinase signal transduction pathway. Once activated, acts as an upstream activator of the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases. May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis. Involved in phosphorylation of WNK4 in response to osmotic stress or hypotonic low-chloride stimulation via the p38 MAPK signal transduction cascade. http://togogenome.org/gene/10090:Bcat1 ^@ http://purl.uniprot.org/uniprot/P24288|||http://purl.uniprot.org/uniprot/Q3TJN1|||http://purl.uniprot.org/uniprot/Q8CBC8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.|||Cytoplasm|||Expressed in brain and kidney. Overexpressed in MYC-induced brain tumors, lymphomas, as well as in a teratocarcinoma cell line.|||Highly expressed at day 9 of embryogenesis. Expression decreases to moderate levels through day 13. In the developing embryo, expressed in the brain, somites and mesenophric tubules.|||Homodimer. http://togogenome.org/gene/10090:Blvra ^@ http://purl.uniprot.org/uniprot/Q9CY64 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Gfo/Idh/MocA family. Biliverdin reductase subfamily.|||Binds 1 zinc ion per subunit.|||Monomer.|||Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IX alpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor. Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7). NADPH, however, is the probable reactant in biological systems.|||cytosol http://togogenome.org/gene/10090:Adra2b ^@ http://purl.uniprot.org/uniprot/P30545|||http://purl.uniprot.org/uniprot/Q925K6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.|||Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.|||Cell membrane|||Interacts with RAB26. Interacts with PPP1R9B. Interacts with GGA1, GGA2 and GGA3.|||Membrane http://togogenome.org/gene/10090:Or4c103 ^@ http://purl.uniprot.org/uniprot/Q8VG21 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gabpb2 ^@ http://purl.uniprot.org/uniprot/P81069 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Heterotetramer of two alpha and two beta subunits. The C-terminal is necessary for the formation of a heterotetrameric GABP-alpha-2/beta-2 complex, and also facilitates homotypic dimerization. Interacts with ADGRB2 (PubMed:16412436).|||High levels in thymus, spleen, kidney and intestine.|||Nucleus|||Transcription factor capable of interacting with purine rich repeats (GA repeats). Must associate with GABP-alpha to bind DNA. http://togogenome.org/gene/10090:Map4k5 ^@ http://purl.uniprot.org/uniprot/Q05BG3|||http://purl.uniprot.org/uniprot/Q8BPM2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Interacts with both SH3 domains of the adapter proteins CRK and CRKL.|||May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway (By similarity).|||May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. http://togogenome.org/gene/10090:Cd72 ^@ http://purl.uniprot.org/uniprot/P21855 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homodimer; disulfide-linked. Associates with CD5. Interacts (tyrosine phosphorylated) with PTPN6/SHP-1.|||Membrane|||Phosphorylated upon engagement of the B-cell receptor, probably by LYN or SYK. Phosphorylation at Tyr-7 is important for interaction with PTPN6/SHP-1.|||Plays a role in B-cell proliferation and differentiation.|||Pre-B-cells and B-cells but not terminally differentiated plasma cells. http://togogenome.org/gene/10090:Ostf1 ^@ http://purl.uniprot.org/uniprot/Q62422 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity.|||Interacts with C-SRC and SMN1. Interacts with FASLG (By similarity).|||The SH3 domain mediates interaction with SMN1. http://togogenome.org/gene/10090:Or8g33 ^@ http://purl.uniprot.org/uniprot/Q8VFD7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Eaf2 ^@ http://purl.uniprot.org/uniprot/K4DI60|||http://purl.uniprot.org/uniprot/Q91ZD6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional transactivator of ELL and ELL2 elongation activities (By similarity). Acts as a transcriptional transactivator of TCEA1 elongation activity.|||Belongs to the EAF family.|||Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with ELL and ELL2 (By similarity). Isoform 1 and isoform 2 interact with TCEA1.|||Expressed in brain and spinal cord at 10 dpc. Expressed in brain, spinal cord, cranial and spinal ganglia, lens, retina, cochlea, olfactory epithelium and pituitary at 12 dpc. Expressed in intestine, bladder endothelium, retinal ganglion cells, nephrons, bronchial epithelium, secretory epithelium of submandibular glands, tubular epithelium of the epididymis, ectodermal invaginations of mammary buds and vibrissae follicles, incisors and molars at 15 dpc.|||Isoform 1 is expressed in ovary, uterus, mammary glands, brain, spleen, liver, lung, thymus, kidney, skeletal muscle, skin and testis. Isoform 2 is expressed in kidney.|||Nucleus speckle http://togogenome.org/gene/10090:Peds1 ^@ http://purl.uniprot.org/uniprot/Q99LQ7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the fatty acid desaturase CarF family.|||Body weight is reduced in homozygous deficient male and female. Deficient mice lack plasmanylethanolamine desaturase activity and have dramatically lowered plasmalogen levels in their tissues.|||Endoplasmic reticulum membrane|||Histidine box-1 and -2 together with other histidine residues are essential for catalytic activity.|||Plasmanylethanolamine desaturase involved in plasmalogen biogenesis in the endoplasmic reticulum membrane. Plasmalogens are glycerophospholipids with a hydrocarbon chain linked by a vinyl ether bond at the glycerol sn-1 position, and are involved in antioxidative and signaling mechanisms. http://togogenome.org/gene/10090:Cdipt ^@ http://purl.uniprot.org/uniprot/A0A0U1RPV3|||http://purl.uniprot.org/uniprot/Q8VDP6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CDP-alcohol phosphatidyltransferase class-I family.|||Catalytic activity is higher with Mg(2+).|||Catalyzes the biosynthesis of phosphatidylinositol (PtdIns) as well as PtdIns:inositol exchange reaction. May thus act to reduce an excessive cellular PtdIns content. The exchange activity is due to the reverse reaction of PtdIns synthase and is dependent on CMP, which is tightly bound to the enzyme.|||Cell membrane|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Nudt13 ^@ http://purl.uniprot.org/uniprot/Q8JZU0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Nudix hydrolase family.|||Divalent metal cations. Mg(2+) or Mn(2+).|||Mitochondrion|||NAD(P)H pyrophosphatase that hydrolyzes NADH into NMNH and AMP, and NADPH into NMNH and 2',5'-ADP (PubMed:28755312). Has a marked preference for the reduced pyridine nucleotides (PubMed:28755312). Does not show activity toward NAD-capped RNAs; the NAD-cap is an atypical cap present at the 5'-end of some RNAs (PubMed:31101919). http://togogenome.org/gene/10090:Ell3 ^@ http://purl.uniprot.org/uniprot/Q80VR2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actively expressed in embryonic stem cells (ES cells), while it is weakly expressed in differentiated cells.|||Belongs to the ELL/occludin family.|||Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2 (By similarity). Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with AFF4.|||Enhancer-binding elongation factor that specifically binds enhancers in embryonic stem cells (ES cells), marks them, and is required for their future activation during stem cell specification. Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. Does not only bind to enhancer regions of active genes, but also marks the enhancers that are in a poised or inactive state in ES cells and is required for establishing proper RNA polymerase II occupancy at developmentally regulated genes in a cohesin-dependent manner. Probably required for priming developmentally regulated genes for later recruitment of the super elongation complex (SEC), for transcriptional activation during differentiation. Required for recruitment of P-TEFb within SEC during differentiation. Probably preloaded on germ cell chromatin, suggesting that it may prime gene activation by marking enhancers as early as in the germ cells. Promoting epithelial-mesenchymal transition (EMT).|||Nucleus http://togogenome.org/gene/10090:Or9q1 ^@ http://purl.uniprot.org/uniprot/Q7TQQ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fabp6 ^@ http://purl.uniprot.org/uniprot/P51162 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Binds to bile acids and is involved in enterohepatic bile acid metabolism. Required for efficient apical to basolateral transport of conjugated bile acids in ileal enterocytes (PubMed:23251388). Stimulates gastric acid and pepsinogen secretion (By similarity).|||Cytoplasm|||Expressed in ovary granulosa and luteal cells.|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. Can bind at least two ligands per molecule, however, the stoichiometry is debated.|||Membrane http://togogenome.org/gene/10090:Foxo6 ^@ http://purl.uniprot.org/uniprot/Q70KY4 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain in areas of the nucleus accumbens, cingulate cortex, parts of the amygdala and in the hippocampus.|||Expressed in developing brain in a specific temporal and spatial pattern.|||Nucleus|||Phosphorylation of Ser-184 is be important in regulating the transacriptional activity.|||Transcriptional activator. http://togogenome.org/gene/10090:Adrm1 ^@ http://purl.uniprot.org/uniprot/Q9JKV1 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although initially described as a cell membrane glycoprotein, ADRM1 is intracellular and non-glycosylated, and has probably no direct role in cell adhesion.|||Belongs to the ADRM1 family.|||Component of the 19S proteasome regulatory particle complex (By similarity). The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (By similarity). Interacts with the proteasomal scaffolding protein PSMD1 (PubMed:18497827). Interacts with deubiquitinase UCHL5; this interaction activates the auto-inhibited UCHL5 by deoligomerizing it (PubMed:18497827). Interacts with UBQLN2 and ubiquitin (PubMed:18497827).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins (PubMed:18497827). This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required (PubMed:18497827). Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair (PubMed:18497827). Within the complex, functions as a proteasomal ubiquitin receptor (PubMed:18497827). Engages and thus activates 19S-associated deubiquitinases UCHL5 and PSMD14 during protein degradation (By similarity). UCHL5 reversibly associate with the 19S regulatory particle whereas PSMD14 is an intrinsic subunit of the proteasome lid subcomplex (By similarity).|||Cytoplasm|||Not N-glycosylated.|||Not O-glycosylated.|||Nucleus|||Present in all tissues examined (at protein level).|||The Pru (pleckstrin-like receptor for ubiquitin) domain mediates interactions with PSMD1 and ubiquitin. Preferential binding to the proximal subunit of 'Lys-48'-linked diubiquitin allows UCHL5 access to the distal subunit.|||Ubiquitinated by UBE3C in response to proteotoxic stress. http://togogenome.org/gene/10090:Hook1 ^@ http://purl.uniprot.org/uniprot/Q8BIL5 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hook family.|||Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (By similarity). Required for spermatid differentiation. Probably involved in the positioning of the microtubules of the manchette and the flagellum in relation to the membrane skeleton (PubMed:12075009).|||Cytoplasm|||Defects in Hook1 are the cause of the azh (abnormal spermatozoon head shape) mutant phenotype, which induces spermatozoa with highly abnormal head morphology that differs drastically from the compact and hook-shaped head of the normal sperm, leading to a strong decrease of fertility.|||Mainly expressed in testis.|||Self-associates (By similarity). Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3 (By similarity). Interacts directly with AKTIP/FTS, HOOK2 and HOOK3 (By similarity). Associates with several subunits of the homotypic vesicular sorting complex (the HOPS complex) including VPS16, VPS18, VPS39 and VPS41; these interactions may be indirect (By similarity). Interacts with CCDC181 (PubMed:28283191). Interacts (via coiled-coil region) with RIMBP3 (via C-terminus) (PubMed:19091768). Interacts with LRGUK (via guanylate kinase-like domain) (PubMed:28003339). Interacts with microtubules (By similarity). May interacts with CLN3 (By similarity). Interacts with AP4M1; the interaction is direct, mediates the interaction between FTS-Hook-FHIP (FHF) complex and AP-4 and the perinuclear distribution of AP-4 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Prss41 ^@ http://purl.uniprot.org/uniprot/Q920S2 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||N-glycosylated.|||Testis-specific. Expressed in spermatogonia and spermatocytes. Expressed in Leydig and Sertoli cells (at protein level). Expressed 2 weeks after birth and remains highly expressed in the sexually mature testis. Expressed in the seminiferous tubules but not in the interstitial tissues. Expressed in type B spermatogonia and spermatocytes at stages between preleptotene and pachytene during the spermatogenesis cycle. http://togogenome.org/gene/10090:Ebf3 ^@ http://purl.uniprot.org/uniprot/O08791|||http://purl.uniprot.org/uniprot/Q5DTH8|||http://purl.uniprot.org/uniprot/Q6NXL3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the COE family.|||First detected at 9.5 dpc.|||Forms either a homodimer or a heterodimer with a related family member.|||Highly expressed in adult olfactory epithelium. In embryo, expressed in epithalamus, hypothalamus, throughout the brainstem and near the ventricular zones of mesencephalon, in rostral rhombencephalon, in vomeronasal organ, at high level in developing retina, developing spinal cord, at low level in dorsal root ganglia, trigeminal ganglia, glossopharyngeal nerve ganglia. Not expressed in developing inner eat.|||Nucleus|||Transcriptional activator (PubMed:9151732). Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3' (By similarity). http://togogenome.org/gene/10090:Nup62cl ^@ http://purl.uniprot.org/uniprot/A2AG10|||http://purl.uniprot.org/uniprot/Q497V0 ^@ Similarity ^@ Belongs to the nucleoporin NSP1/NUP62 family. http://togogenome.org/gene/10090:Scgb1b29 ^@ http://purl.uniprot.org/uniprot/D2XZ31 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Mad2l2 ^@ http://purl.uniprot.org/uniprot/Q9D752 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres. May also regulate another aspect of cellular response to DNA damage through regulation of the JNK-mediated phosphorylation and activation of the transcriptional activator ELK1. Inhibits the FZR1- and probably CDC20-mediated activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Regulates TCF7L2-mediated gene transcription and may play a role in epithelial-mesenchymal transdifferentiation.|||Chromosome|||Cytoplasm|||Homooligomer (By similarity). Heterodimer with REV3L (By similarity). This dimer forms the minimal DNA polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase catalytic activity, although its activity is very low in this context (By similarity). Component of the tetrameric Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is the fully active form of DNA polymerase zeta (By similarity). Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7. Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus (By similarity). Interacts with REV1 (PubMed:14657033). Interacts with ADAM9 (By similarity). Interacts with CHAMP1 (By similarity). Interacts with FZR1 (in complex with the anaphase promoting complex APC) (By similarity). May interact with CDC20 (By similarity). Interacts with RAN (By similarity). Interacts with ELK1; the interaction is direct and recruits MAD2L2 to ELK1-specific promoters (By similarity). May interact with the JNK kinases MAPK8 and/or MAPK9 to stimulate ELK1 phosphorylation and transcriptional activity upon DNA damage (By similarity). Interacts with TCF7L2; prevents its binding to promoters and negatively modulates its transcriptional activity (By similarity). Interacts with YY1AP1 (By similarity). Interacts with PRCC; the interaction is direct (By similarity). Interacts with POGZ (By similarity).|||Nucleus|||spindle http://togogenome.org/gene/10090:Gm6614 ^@ http://purl.uniprot.org/uniprot/L7N251 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Mogs ^@ http://purl.uniprot.org/uniprot/Q80UM7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 63 family.|||Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Lpcat4 ^@ http://purl.uniprot.org/uniprot/Q6NVG1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Displays acyl-CoA-dependent lysophospholipid acyltransferase activity with a subset of lysophospholipids as substrates; converts lysophosphatidylethanolamine to phosphatidylethanolamine, 1-alkenyl-lysophatidylethanolamine to 1-alkenyl-phosphatidylethanolamine, lysophosphatidylglycerol and alkyl-lysophosphatidylcholine to phosphatidylglycerol and alkyl-phosphatidylcholine, respectively. In contrast, has no lysophosphatidylinositol, glycerol-3-phosphate, diacylglycerol or lysophosphatidic acid acyltransferase activity. Prefers long chain acyl-CoAs (C16, C18) as acyl donors (By similarity). Converts lysophosphatidylcholine to phosphatidycholine (PubMed:18156367).|||Endoplasmic reticulum membrane|||Widely expressed with much higher level in brain. Expressed in erythroleukemic cells but not in reticulocytes. http://togogenome.org/gene/10090:Fubp3 ^@ http://purl.uniprot.org/uniprot/Q8BYI4 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Mcoln1 ^@ http://purl.uniprot.org/uniprot/Q99J21 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN1 sub-subfamily.|||Cell membrane|||Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments (By similarity). Channel function is transiently modulated by changes in Ca(2+), and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca(2+) and H(+) is suggested (PubMed:29019981). Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) (PubMed:29019981).|||Cytoplasmic vesicle membrane|||Homotetramer (PubMed:29019981). Homooligomer. Can heterooligomerize with MCOLN2 or MCOLN3; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific. Interacts with PDCD6. Interacts with TMEM163. Interacts with LAPTM4B (By similarity).|||Late endosome membrane|||Lysosome membrane|||May contribute to cellular lipase activity within the late endosomal pathway or at the cell surface which may be involved in processes of membrane reshaping and vesiculation, especially the growth of tubular structures. However, it is not known, whether it conveys the enzymatic activity directly, or merely facilitates the activity of an associated phospholipase.|||Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis (PubMed:29019981). Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy. Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (PubMed:23993788, PubMed:27623384). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events. By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (By similarity). Functions as a Fe(2+) permeable channel in late endosomes and lysosomes. Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (By similarity). In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (PubMed:17050035).|||Palmitoylated; involved in association with membranes.|||Phosphorylation by PKA inhibits channel activity. Dephosphorylation increases activity.|||Proteolytically cleaved probably involving multiple lysosomal proteases including cathepsin B; inhibits lysosomal channel activity.|||The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.|||Up-regulated by nutrient starvation.|||Widely expressed, with the highest expression in brain, liver and kidney.|||phagocytic cup|||phagosome membrane http://togogenome.org/gene/10090:Epha3 ^@ http://purl.uniprot.org/uniprot/Q8BRB1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Arl6ip1 ^@ http://purl.uniprot.org/uniprot/Q9JKW0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ARL6ip family.|||Endomembrane system|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Expressed in the cerebral cortex, cerebellum, hippocampus, olfactory bulbs, medulla oblongate and limbic system (at protein level). Ubiquitous (PubMed:18684713). Expressed in all hematopoietic cell lineages, with highest levels in early myeloid progenitor cells.|||Homooligomer (By similarity). Heterodimer with ARL6IP5 (PubMed:18684713). Interacts with ARL6 (PubMed:10508919). Interacts with TMEM33. Interacts with ATL1 (By similarity).|||Positively regulates SLC1A1/EAAC1-mediated glutamate transport by increasing its affinity for glutamate in a PKC activity-dependent manner. Promotes the catalytic efficiency of SLC1A1/EAAC1 probably by reducing its interaction with ARL6IP5, a negative regulator of SLC1A1/EAAC1-mediated glutamate transport (PubMed:18684713). Plays a role in the formation and stabilization of endoplasmic reticulum tubules. Negatively regulates apoptosis, possibly by modulating the activity of caspase-9 (CASP9). Inhibits cleavage of CASP9-dependent substrates and downstream markers of apoptosis but not CASP9 itself. May be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation (By similarity).|||The transmembrane domains are required for its ability to shape the endoplasmic reticulum membrane into tubules. http://togogenome.org/gene/10090:Gna11 ^@ http://purl.uniprot.org/uniprot/P21278|||http://purl.uniprot.org/uniprot/Q3UPA1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(q) subfamily.|||Cell membrane|||Cytoplasm|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with RGS22. Interacts with NTSR1.|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:9687499). Acts as an activator of phospholipase C (PubMed:9687499). Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs) (By similarity). Together with GNAQ, required for heart development (PubMed:9687499).|||No visible phenoptype (PubMed:9687499). Mice lacking Gnaq and Gna11 are embryonic lethal due to cardiomyocyte hypoplasia (PubMed:9687499). Mice lacking Gnaq and with one single intact copy of Gna11, as well as mice lacking Gna11 and with one single intact copy of Gnaq die shortly after birth; lethality is caused by heart malformations (PubMed:9687499). Newborns display craniofacial defects (PubMed:9687499). http://togogenome.org/gene/10090:Mycbp2 ^@ http://purl.uniprot.org/uniprot/Q7TPH6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (By similarity). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (By similarity). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (By similarity). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (By similarity). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration (PubMed:14729956, PubMed:17901218, PubMed:18031680). Required for the formation of major central nervous system axon tracts (PubMed:17901218, PubMed:18031680). Required for proper axon growth by regulating axon navigation and axon branching: acts by regulating the subcellular location and stability of MAP3K12/DLK (PubMed:18031680). Required for proper localization of retinogeniculate projections but not for eye-specific segregation (PubMed:19371781, PubMed:21324225). Regulates axon guidance in the olfactory system (PubMed:23525682). Involved in Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons: acts by promoting destabilization of NMNAT2, probably via ubiquitination of NMNAT2 (PubMed:23665224). Catalyzes ubiquitination of threonine and/or serine residues on NMNAT2, consequences of threonine and/or serine ubiquitination are however unknown (By similarity). Regulates the internalization of TRPV1 in peripheral sensory neurons (PubMed:21098484). May mediate ubiquitination and subsequent proteasomal degradation of TSC2/tuberin (By similarity). Independently of the E3 ubiquitin-protein ligase activity, also acts as a guanosine exchange factor (GEF) for RAN in neurons of dorsal root ganglia (PubMed:26304119). May function as a facilitator or regulator of transcriptional activation by MYC (By similarity). Acts in concert with HUWE1 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529).|||Autoubiquitinated.|||Belongs to the RING-Cys relay (RCR) family.|||Dynamically expressed in embryonic nervous system from 8.5 dpc through 18.5 dpc (PubMed:14729956, PubMed:18031680). At 10.5 dpc, shortly after the birth of the first motor neurons, highly expressed in the developing motor columns, dorsal root ganglion and newly formed neurons within the dorsal neural tube (PubMed:18031680). As embryos develop to 11.5 dpc, expression levels increase in the dorsal root ganglion and expression in the spinal cord expandes as the number of postmitotic neurons increase (PubMed:18031680). By 12.5 dpc expression is widespread within the spinal cord (PubMed:18031680).|||Expression is mostly restricted to the nervous system, including expression in motor and sensory axons (PubMed:18031680). During postnatal development, expression is particularly strong in the cerebellum, hippocampus and retina (PubMed:14729956). Lower levels of expression are observed throughout the cerebral cortex (PubMed:14729956).|||Interacts with MYC (By similarity). Interacts with TSC2 (tuberin) when TSC2 is in complex with TSC1 (hamartin) (By similarity). Interacts with FBXO45 (PubMed:19398581). Interacts with RAE1 (By similarity). Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with (sumoylated) RANGAP1; interaction with sumoylated RANGAP1 inhibits E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119). Interacts with RAN (PubMed:26304119). Interacts with ATP13A2; the interaction inhibits the ubiquitination of TSC2 by MYCBP2 (By similarity). Interacts with USP11 (By similarity).|||Lethality caused by defects in neuromuscular development (PubMed:17901218). Mice die at birth without taking a breath: phrenic nerves are markedly narrower and contain fewer axons than controls (PubMed:17901218). Mice display incomplete innervation of the diaphragm by the phrenic nerve (PubMed:14729956, PubMed:17901218). Intercostal muscles are completely innervated, but show dysmorphic nerve terminals (PubMed:14729956, PubMed:17901218). Sensory neuron terminals in the diaphragm are abnormal and neuromuscular junctions show excessive sprouting of nerve terminals, consistent with inadequate presynaptic stimulation of the muscle (PubMed:14729956). Embryos display motor axon misprojections and stalling: motor axons are error-prone and wander inefficiently at choice points within embryos (PubMed:18031680). Conditional knockout mice lacking Mycbp2 in the retina, exhibit no gross retinal developmental defects; mutants retain normal retinal lamination, monocular segregation and spontaneous retinal wave activity, but mutant retinal ganglion cells exhibit ipsilateral projection to an improper region of the dorsal lateral geniculate nucleus (dLGN) (PubMed:19371781, PubMed:21324225). Conditional knockout mice lacking Mycbp2 in peripheral sensory neurons display prolonged thermal hyperalgesia: defects are caused by constitutive activation of MAP kinase p38 (Mapk11, Mapk12, Mapk13 and/or Mapk14), leading to inhibit internalization of Trpv1 (PubMed:21098484).|||Nucleus|||The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners.|||The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.|||axon|||cytoskeleton http://togogenome.org/gene/10090:Fam177a ^@ http://purl.uniprot.org/uniprot/Q8BR63 ^@ Similarity ^@ Belongs to the FAM177 family. http://togogenome.org/gene/10090:Plpp7 ^@ http://purl.uniprot.org/uniprot/Q91WB2 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Endoplasmic reticulum membrane|||Highly expressed in heart and muscle.|||Homo- and heterooligomer. Interacts with MTOR; controls MTOR-dependent IGF2 expression during myoblast differentiation.|||Membrane|||Nucleus envelope|||Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling. Has no detectable enzymatic activity. Knockdown in myoblasts strongly promotes differentiation, whereas overexpression represses myogenesis.|||Up-regulated during myoblast differentiation. http://togogenome.org/gene/10090:Cdkl4 ^@ http://purl.uniprot.org/uniprot/Q3TZA2 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||The [NKR]KIAxRE motif seems to be a cyclin-binding region. http://togogenome.org/gene/10090:Slc22a23 ^@ http://purl.uniprot.org/uniprot/Q3UHH2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Membrane http://togogenome.org/gene/10090:Or2y6 ^@ http://purl.uniprot.org/uniprot/Q7TQT7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbm15 ^@ http://purl.uniprot.org/uniprot/Q0VBL3 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM Spen family.|||Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (By similarity). Interacts with RBPJ (PubMed:17283045). Interacts (via SPOC domain) with SETD1B (By similarity). Interacts with NXF1, the interaction is required to promote mRNA export (By similarity). Interacts with SF3B1 (By similarity).|||Contaminating sequence.|||Embryonic lethality around E9.5 (PubMed:17376872, PubMed:18981216). Early embryos show growth retardation and incomplete closure of the notochord, as well as placental defects in the spongiotrophoblast and syncytiotrophoblast layers, resulting in an arrest of vascular branching morphogenesis (PubMed:18981216). Conditional knockout mice lacking Rbm15 within the hematopoietic compartment display a loss of peripheral B-cells due to a block in pro/pre-B differentiation, as well as a myeloid and megakaryocytic expansion in spleen and bone marrow (PubMed:17376872).|||Methylated at Arg-577 by PRMT1, leading to promote ubiquitination by CNOT4 and subsequent degradation by the proteasome.|||Nucleus envelope|||Nucleus membrane|||Nucleus speckle|||RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as hematopoietic cell homeostasis, alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA (PubMed:29535189). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29535189). Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex (PubMed:29535189). Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist (By similarity). Required for the development of multiple tissues, such as the maintenance of the homeostasis of long-term hematopoietic stem cells and for megakaryocyte (MK) and B-cell differentiation (PubMed:17283045, PubMed:17376872, PubMed:18981216, PubMed:25468569). Regulates megakaryocyte differentiation by regulating alternative splicing of genes important for megakaryocyte differentiation; probably regulates alternative splicing via m6A regulation (By similarity). Required for placental vascular branching morphogenesis and embryonic development of the heart and spleen (PubMed:18981216). Acts as a regulator of thrombopoietin response in hematopoietic stem cells by regulating alternative splicing of MPL (PubMed:25468569). May also function as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs which are present in many retrotransposons that require to be exported prior to splicing (By similarity). High affinity binding of pre-mRNA to RBM15 may allow targeting of the mRNP to the export helicase DBP5 in a manner that is independent of splicing-mediated NXF1 deposition, resulting in export prior to splicing (By similarity). May be implicated in HOX gene regulation (By similarity).|||Ubiquitinated by CNOT4 following methylation at Arg-577 by PRMT1.|||nucleoplasm http://togogenome.org/gene/10090:Bbs10 ^@ http://purl.uniprot.org/uniprot/Q9DBI2 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of a complex composed at least of MKKS, BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 and CCT8.|||Intron retention. Several introns.|||Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis. Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation.|||cilium http://togogenome.org/gene/10090:Slco4c1 ^@ http://purl.uniprot.org/uniprot/Q8BGD4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Dramatically down-regulated 1 day after gonadectomy.|||Mediates the transport of organic anions such as steroids (estrone 3-sulfate, chenodeoxycholate, glycocholate) and thyroid hormones (3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4)), in the kidney. Capable of transporting cAMP and pharmacological substances such as digoxin, ouabain and methotrexate. Transport is independent of sodium, chloride ion, and ATP. Transport activity is stimulated by an acidic extracellular environment due to increased substrate affinity to the transporter (By similarity). The driving force for this transport activity is currently not known (By similarity). The role of hydrogencarbonate (HCO3(-), bicarbonate) as the probable counteranion that exchanges for organic anions is still not well defined (By similarity). Functions as an uptake transporter at the apical membrane, suggesting a role in renal reabsorption (By similarity). Involved in the renal secretion of the uremic toxin ADMA (N(omega),N(omega)-dimethyl-L-arginine or asymmetrical dimethylarginine), which is associated to cardiovascular events and mortality, and the structurally related amino acids L-arginine and L-homoarginine (a cardioprotective biomarker). Can act bidirectionally, suggesting a dual protective role of this transport protein; exporting L-homoarginine after being synthesized in proximal tubule cells, and mediating uptake of ADMA from the blood into proximal tubule cells where it is degraded by the enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) (By similarity). May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells (PubMed:16641146). This ion-transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation (PubMed:16641146). May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg (PubMed:16641146).|||Strongly expressed in initial segment of epididymis and seminal vesicles. http://togogenome.org/gene/10090:Mterf3 ^@ http://purl.uniprot.org/uniprot/Q8R3J4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mTERF family.|||Binds promoter DNA and regulates initiation of transcription (By similarity). Required for normal mitochondrial transcription and translation, and for normal assembly of mitochondrial respiratory complexes (PubMed:17662942, PubMed:23300484). Required for normal mitochondrial function (PubMed:17662942, PubMed:23300484). Maintains 16S rRNA levels and functions in mitochondrial ribosome assembly by regulating the biogenesis of the 39S ribosomal subunit (PubMed:17662942, PubMed:23300484).|||Contains seven structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a superhelical structure with a solenoid shape.|||Embryonic lethality, due to severe mitochondrial dysfunction. Embryos are much smaller than normal and none survive past 10.5 dpc.|||Mitochondrion http://togogenome.org/gene/10090:Gm20827 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXW2 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Gvin1 ^@ http://purl.uniprot.org/uniprot/L7N451 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.|||Nucleus http://togogenome.org/gene/10090:Gramd2a ^@ http://purl.uniprot.org/uniprot/Q3V3G7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation ^@ Cell membrane|||Endoplasmic reticulum membrane|||GRAM domain is required for specific location to endoplasmic reticulum-plasma membrane contact sites (EPCS). Mediates interaction to phosphatidylinositol lipids and binding to plasma membrane.|||Participates in the organization ofendoplasmic reticulum-plasma membrane contact sites (EPCS) with pleiotropic functions including STIM1 recruitment and calcium homeostasis. Constitutive tether that co-localize with ESYT2/3 tethers at endoplasmic reticulum-plasma membrane contact sites in a phosphatidylinositol lipid-dependent manner. Pre-marks the subset of phosphtidylinositol 4,5-biphosphate (PI(4,5)P2)-enriched EPCS destined for the store operated calcium entry pathway (SOCE).|||Phosphorylated. http://togogenome.org/gene/10090:Pramel37 ^@ http://purl.uniprot.org/uniprot/Q6P8K3 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Spsb2 ^@ http://purl.uniprot.org/uniprot/O88838 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPSB family.|||Component of the probable ECS(SPSB2) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB2 (By similarity). Interacts with CUL5, RNF7, ELOB and ELOC (By similarity). Interacts with MET (PubMed:16369487). Interacts (via B30.2/SPRY domain) with PAWR; this interaction occurs in association with the Elongin BC complex (PubMed:16369487, PubMed:20561531). Interacts with NOS2.|||Cytoplasm|||Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20603330). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (PubMed:20603330). Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By similarity).|||cytosol http://togogenome.org/gene/10090:Cyria ^@ http://purl.uniprot.org/uniprot/Q8BHZ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CYRI family.|||Interacts with RAC1 (GTP-bound form preferentially).|||May negatively regulate RAC1 signaling and RAC1-driven cytoskeletal remodeling. May regulate chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions.|||Membrane http://togogenome.org/gene/10090:Parp11 ^@ http://purl.uniprot.org/uniprot/Q8BML7|||http://purl.uniprot.org/uniprot/Q8CFF0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Auto-mono-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Knockout mice are viable and are born in normal Mendelian ratios. Knockout males, but not females, exhibit a striking fertility defect, with the majority of males being sterile and a minority producing infrequent and small litters. Sperm from mutant mice exhibits mild to severe teratozoospermia, with structural defects in elongating spermatid nuclear envelope and chromatin detachment associated with abnormal nuclear shaping.|||Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins (By similarity). Plays a role in nuclear envelope stability and nuclear remodeling during spermiogenesis (PubMed:25673562).|||Predominantly expressed in testis, preferentially in postmeiotic germ cells. Also detectable in other tissues, including liver, lung, spleen, thymus and brain.|||Undetectable in testis until postnatal day 18. Sharply up-regulated from postnatal days 18 to 21. This timeframe corresponds to the appearance of the first spermatids of the first wave of spermatogenesis just before initiation of elongation. Remains elevated in adult animals.|||nuclear pore complex http://togogenome.org/gene/10090:Snap91 ^@ http://purl.uniprot.org/uniprot/E9Q9A3|||http://purl.uniprot.org/uniprot/Q3TWS4|||http://purl.uniprot.org/uniprot/Q61548 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptins are components of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Binding of AP180 to clathrin triskelia induces their assembly into 60-70 nm coats.|||Belongs to the PICALM/SNAP91 family.|||Binds AP2A2. Interacts with AP2B1; clathrin competes with SNAP91 (By similarity).|||Brain. Associated with the synapses.|||Cell membrane|||Developmentally regulated in a pattern coincident with active synaptogenesis and synaptic maturation.|||Membrane|||Possesses a three domain structure: the N-terminal 300 residues harbor a clathrin binding site, an acidic middle domain 450 residues, interrupted by an Ala-rich segment, and the C-terminal domain (166 residues).|||Thr-310 can be modified by the addition of N-acetylglucosamine which can be further phosphorylated. There is no evidence for direct Thr-310 phosphorylation (By similarity).|||coated pit http://togogenome.org/gene/10090:Rfpl4 ^@ http://purl.uniprot.org/uniprot/Q8VH31 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in growing oocytes and early embryos.|||Expressed in the ovaries and oocytes (at protein level) (PubMed:12525704, PubMed:11850190). Expression restricted to gonads. In testis, present at later stages of spermatogeneis and abundant in elongating spermatids.|||Interacts with PSMB1, UBE2A and CCNB1.|||Nucleus http://togogenome.org/gene/10090:Or8b42 ^@ http://purl.uniprot.org/uniprot/Q7TRD1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ankib1 ^@ http://purl.uniprot.org/uniprot/Q6ZPS6 ^@ Caution|||Domain|||Function|||Similarity ^@ Belongs to the RBR family.|||Lacks one Cys residue in the IBR-type zinc finger domain that is one of the conserved features of the family.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.|||Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes and then transfers it to substrates. http://togogenome.org/gene/10090:Phf21a ^@ http://purl.uniprot.org/uniprot/Q6ZPK0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. In the complex, it interacts directly with HDAC1, HDAC2, HMG20B/BRAF35, KDM1A and RCOR1/CoREST (By similarity).|||Component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it may act as a scaffold. Inhibits KDM1A-mediated demethylation of 'Lys-4' of histone H3 in vitro, suggesting a role in demethylation regulation (By similarity).|||Expressed in the brain and testis. Weakly or not expressed in other tissues tested. Localized throughout the central nervous system (CNS) in brain, including the cerebellum, hippocampus, and cortex. Notably present in neuronal cells of granular cell layer and dentate gyrus in cerebellum and hippocampus, respectively. In the seminiferous tubules, the signals it is present strongly in spermatocytes, and weakly in spermatogonia and round spermatids. In some cases, it is also observed solely in spermatocytes (at protein level).|||Nucleus http://togogenome.org/gene/10090:Wdr33 ^@ http://purl.uniprot.org/uniprot/Q8K4P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat WDR33 family.|||Component of the cleavage and polyadenylation specificity factor (CPSF) module of the pre-mRNA 3'-end processing complex. Interacts with CPSF3/CPSF73 (By similarity).|||Essential for both cleavage and polyadenylation of pre-mRNA 3' ends.|||Most highly expressed in testis.|||Nucleus http://togogenome.org/gene/10090:Smim24 ^@ http://purl.uniprot.org/uniprot/Q0VG18 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rab34 ^@ http://purl.uniprot.org/uniprot/Q64008 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasm|||Golgi apparatus|||Interacts with RILP.|||Transport protein involved in the redistribution of lysosomes to the peri-Golgi region (PubMed:12475955). Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis (By similarity). Plays a role in the fusion of phagosomes with lysosomes (By similarity). Acts also as a positive regulator of hedgehog signaling and regulates ciliary function (PubMed:29290584).|||cilium|||phagosome|||phagosome membrane http://togogenome.org/gene/10090:Pml ^@ http://purl.uniprot.org/uniprot/A0A068EW80|||http://purl.uniprot.org/uniprot/D3Z3A6|||http://purl.uniprot.org/uniprot/Q60953 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-497 is essential for its nuclear localization. Deacetylated at Lys-497 by SIRT1 and this deacetylation promotes PML control of PER2 nuclear localization (By similarity).|||Binds arsenic via the RING-type zinc finger.|||Cytoplasm|||Early endosome membrane|||Endoplasmic reticulum membrane|||Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (By similarity). Positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts as both a negative regulator of PPARGC1A acetylation and a potent activator of PPAR signaling and fatty acid oxidation. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates PER2 nuclear localization and circadian function. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. Required for normal development of the brain cortex during embryogenesis. Plays a role in granulopoiesis or monopoiesis of myeloid progenitor cells. May play a role regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Shows antiviral activity towards lymphocytic choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV).|||Key component of PML bodies. PML bodies are formed by the interaction of PML homodimers (via SUMO-binding motif) with sumoylated PML, leading to the assembly of higher oligomers. Several types of PML bodies have been observed. PML bodies can form hollow spheres that can sequester target proteins inside. Interacts (via SUMO-binding motif) with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 phosphorylation at 'Ser-20' and prevents its proteasomal degradation. Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby preventing ubiquitination of p53/TP53. Interaction with PML-RARA oncoprotein and certain viral proteins causes disassembly of PML bodies and abolishes the normal PML function. Interacts with TERT, SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). Interacts with Lassa virus Z protein and rabies virus phosphoprotein. Interacts (in the cytoplasm) with TGFBR1, TGFBR2 and PKM. Interacts (via the coiled-coil domain and when sumoylated) with SATB1. Interacts with UBE2I; the interaction is enhanced by arsenic binding. Interacts with SMAD2, SMAD3, DAXX, RPL11, HIPK2 and MTOR. Interacts with ITPR3, PPP1A and RB1. Interacts with RNF4, NLRP3, MAGEA2, RBL2, PER2, E2F4 and MAPK7/BMK1. Interacts with CSNK2A1 and CSNK2A3. Interacts with ANKRD2; the interaction is direct. Interacts with PPARGC1A and KAT2A. Interacts (via SUMO-interacting motif) with sumoylated MORC3 (By similarity). Interacts with TRIM16. Interacts with PRDM1 (By similarity). Interacts (via RING-type zinc finger) with EIF4E; the interaction reduces EIF4E affinity for the 5' m7G cap of mRNA, thus reducing nuclear export of cyclin CCND1 (PubMed:11500381, PubMed:11575918).|||Mice are born at the expected Mendelian rate and are fertile. They show leukopenia with reduced levels of circulating granulocytes and myeloid cells. They are highly susceptible to infections, causing a reduced life span. Mice do not exhibit normal apoptosis of hematopoietic stem cells after DNA damage due to irradiation. They do not exhibit normal apoptosis in response to FAS, TNF, TGFB1, interferons and ceramide, and show impaired activation of caspases in response to pro-apoptotic stimuli. Mice are highly susceptible to chemical carcinogens. Mice display accelerated revascularization after ischemia. Newborns have smaller brains with a reduced size of the brain cortex. Mice display aberrant learning and memory, lower levels of anxiety-like behavior and specific deficits in long-term plasticity. Mice display a compromised endogenous circadian clock with reduced precision and stability of the period length.|||Nucleus|||PML body|||Phosphorylation is a major regulatory mechanism that controls PML protein abundance and the number and size of PML nuclear bodies (PML-NBs). Phosphorylated in response to DNA damage, probably by ATR. HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage. MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation. CK2-mediated phosphorylation at Ser-575 primes PML ubiquitination via an unidentified ubiquitin ligase (By similarity).|||Sumoylation regulates PML's: stability in response to extracellular or intracellular stimuli, transcription directly and indirectly, through sequestration of or dissociation of the transcription factors from PML-NBs, ability to regulate apoptosis and its anti-viral activities. It is also essential for: maintaining proper PML nuclear bodies (PML-NBs) structure and normal function, recruitment of components of PML-NBs, the turnover and retention of PML in PML-NBs and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation. Sumoylation on Lys-165 is a prerequisite for sumoylation on Lys-70. Lys-70 and Lys-165 are sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation. Sumoylation at Lys-500 by RANBP2 is essential for the proper assembly of PML-NBs. Desumoylated by SENP1, SENP2, SENP3, SENP5 and SENP6 (By similarity).|||The Sumo interaction motif (SIM) is required for efficient ubiquitination, recruitment of proteasome components within PML-NBs and PML degradation in response to arsenic trioxide.|||The coiled-coil domain mediates a strong homo/multidimerization activity essential for core assembly of PML-NBs.|||Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP, BCR(KLHL20) E3 ubiquitin ligase complex, SIAH1 or SIAH2 and leading to subsequent proteasomal degradation. 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity). Ubiquitination by RNF111 is polysumoylation-dependent (PubMed:23530056). Ubiquitination by BCR(KLHL20) E3 ubiquitin ligase complex requires CDK1/2-mediated phosphorylation at Ser-528 which in turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further potentiates PML interaction with KLHL20 (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Abcc3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J015|||http://purl.uniprot.org/uniprot/B2RX12 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (By similarity). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (PubMed:15814571, PubMed:16225954). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (By similarity).|||Basal cell membrane|||Basolateral cell membrane|||Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Cell membrane|||Deficient mice do not exhibit any overt phenotype under normal conditions. However when challenged with cholestasis induced by bile duct ligation, increased levels of hepatic bile salts and lower serum levels of bilirubin glucuronide are observed, suggesting that Abcc3 provides an alternative route for removal from the liver of these substrates under cholestatic conditions.|||Detected throughout the gastrointestinal tract, liver, lung, pancreas, bladder, gall bladder and at low levels in the adrenal gland.|||Membrane http://togogenome.org/gene/10090:Tmem59l ^@ http://purl.uniprot.org/uniprot/Q7TNI2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM59 family.|||Golgi apparatus membrane|||Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of APP. Inhibits APP transport to the cell surface and further shedding (By similarity). http://togogenome.org/gene/10090:Aasdh ^@ http://purl.uniprot.org/uniprot/Q80WC9 ^@ Caution|||Function|||Induction|||Similarity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Covalently binds beta-alanine in an ATP-dependent manner to form a thioester bond with its phosphopantetheine group and transfers it to an as yet unknown acceptor via an amide bond. May be required for a post-translational protein modification or for post-transcriptional modification of an RNA.|||Has been shown to be up-regulated by a lysine-rich diet (PubMed:12712191). However, levels of expression have also been shown not to be significantly changed even when diets differ markedly in PQQ and lysine content (PubMed:17029795).|||In invertebrates, the aminoadipate-semialdehyde dehydrogenase reaction is a key step of the L-lysine biosynthesis pathway which is not fully conserved in vertebrates and it has been suggested that this protein participates in the reverse reaction i.e. in lysine catabolism (PubMed:12712191). However, this is unlikely to be the case as no dehydrogenase activity has been detected and the authentic mammalian 2-aminoadipate semialdehyde dehydrogenase has been identified as ALDH7A1 (PubMed:24467666).|||Was suggested to bind pyrroloquinoline quinone (PQQ) based on prediction tools and indirect results (PubMed:12712191). However, this has not been confirmed in other publications (PubMed:15689995, PubMed:15689994). http://togogenome.org/gene/10090:Acaa1a ^@ http://purl.uniprot.org/uniprot/Q921H8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the thiolase-like superfamily. Thiolase family.|||Homodimer. Interacts (via PTS2-type peroxisomal targeting signal region) with PEX7; leading to its translocation into peroxisomes.|||Mainly expressed in liver and intestine.|||Peroxisome|||Responsible for the thiolytic cleavage of straight chain 3-keto fatty acyl-CoAs (3-oxoacyl-CoAs) (Probable). Plays an important role in fatty acid peroxisomal beta-oxidation (Probable). Catalyzes the cleavage of short, medium, long, and very long straight chain 3-oxoacyl-CoAs (By similarity).|||The PTS2-type peroxisomal targeting signal, which mediates interaction with PEX7 and localization to peroxisomes, is cleaved following import into peroxisomes. http://togogenome.org/gene/10090:Frs3 ^@ http://purl.uniprot.org/uniprot/Q91WJ0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that links FGF and NGF receptors to downstream signaling pathways. Involved in the activation of MAP kinases. Down-regulates ERK2 signaling by interfering with the phosphorylation and nuclear translocation of ERK2.|||Binds NGFR, GRB2, PTPN11 and ERK2 (By similarity). Binds FGFR1 and NTRK1.|||Membrane|||Phosphorylated on tyrosine residues upon stimulation by BFGF or NGFB. Phosphorylated by ULK2 in vitro. http://togogenome.org/gene/10090:Eif1ad7 ^@ http://purl.uniprot.org/uniprot/Q8BX20 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Esrrb ^@ http://purl.uniprot.org/uniprot/E9QKA2|||http://purl.uniprot.org/uniprot/G5E8P8|||http://purl.uniprot.org/uniprot/Q61539|||http://purl.uniprot.org/uniprot/Q80VS1|||http://purl.uniprot.org/uniprot/Q8CCV5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by PCAF/KAT2 (in vitro).|||Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Binds DNA as a monomer (By similarity). Interacts with NR0B1; represses ESRRB activity at the GATA6 promoter (PubMed:27601327, PubMed:23508100). Interacts with NANOG; reciprocally modulates their transcriptional activities and activates POU5F1 expression (PubMed:18957414). Interacts with NCOA3; mediates the interaction between ESRRB and RNA polymerase II complexes and allows NCOA3 corecruitment to ESRRB, KLF4, NANOG, and SOX2 enhancer regions to trigger ESRRB-dependent gene activation involved in self-renewal and pluripotency (PubMed:23019124). Interacts with KDM1A; co-occupes the core set of ESRRB targets including ELF5 and EOMES (PubMed:26206133). Interacts with the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12; ESRRB is probably not a core component of the integrator complex and associates to integrator via its interaction with INTS1 and INTS9; attracts the transcriptional machinery (PubMed:26206133). Interacts with JARID2 (PubMed:26523946). Interacts with POU5F1; recruits ESRRB near the POU5F1-SOX2 element in the NANOG proximal promoter leading to activation of NANOG expression; the interaction is DNA independent (PubMed:18662995).|||Chromosome|||Cytoplasm|||Found in the extra-embryonic ectoderm at 5.5 dpc, 6 dpc and 6.5 dpc. At 7.5 dpc, is exclusively detected in chorion, and at 8.5 dpc is present only at its free margin. Expression is not detected in the ectoplacental cone at any stage of development, nor is placental expression detected after 8.5 dpc.|||Highly expressed in undifferentiated ESCs (PubMed:23508100). Expressed in immature horizontal cells and in rod photoreceptors at intermediate and late stages of differentiation (PubMed:20534447). Expressed in endolymph-producing epithelial cells (PubMed:17765677).|||Homozygote Esrrb mutant embryos die at 10.5 dpc. They have severely impaired placental formation. The mutants display abnormal chorion development associated with an overabundance of trophoblast giant cells and a severe deficiency of diploid trophoblast (PubMed:9285590). Conditional knockdown mice exhibit head bobbing and spinning and running in circles and have hearing impairment (PubMed:17765677).|||Induced by NANOG (PubMed:23040477). Induced by GSK3 inhibition through inhibition of TCF3 repression. Repressed by TCF3 (PubMed:23040478). Reduced upon differentiation induced by LIF depletion (PubMed:23508100).|||Nucleus|||Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcriptional activity (PubMed:27601327, PubMed:23169531, PubMed:23508100, PubMed:26206133, PubMed:20534447, PubMed:18662995, PubMed:18957414, PubMed:27723719, PubMed:23019124). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways (PubMed:18957414, PubMed:26206133, PubMed:20534447, PubMed:23040478, PubMed:23040477, PubMed:23019124, PubMed:23169531). Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells (PubMed:26206133). Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (PubMed:20534447). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:18662995, PubMed:23508100, PubMed:18957414). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (By similarity). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase (PubMed:27723719). Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation (PubMed:23019124, PubMed:23169531, PubMed:18662995, PubMed:26206133). This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program (PubMed:23169531). Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (PubMed:9285590, PubMed:17765677). http://togogenome.org/gene/10090:Mrpl21 ^@ http://purl.uniprot.org/uniprot/Q9D1N9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL21 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Wdr18 ^@ http://purl.uniprot.org/uniprot/Q4VBE8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat IPI3/WDR18 family.|||Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9 (PubMed:22872859). Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts with pre-60S ribosome particles (By similarity).|||Cytoplasm|||Dynein axonemal particle|||Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (By similarity). May play a role during development (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Slc35e1 ^@ http://purl.uniprot.org/uniprot/Q8CD26 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPT transporter family. SLC35E subfamily.|||Membrane|||Putative transporter. http://togogenome.org/gene/10090:Barhl2 ^@ http://purl.uniprot.org/uniprot/Q7TNS3|||http://purl.uniprot.org/uniprot/Q8VIB5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BAR homeobox family.|||Nucleus|||Potential regulator of neural basic helix-loop-helix genes. It may down-regulate expression of ASCL1 and, within the thalamus, up-regulate NGN2, thereby regulating distinct patterns of neuronal differentiation (By similarity). http://togogenome.org/gene/10090:Nfic ^@ http://purl.uniprot.org/uniprot/P70255|||http://purl.uniprot.org/uniprot/Q3UHA6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CTF/NF-I family.|||Binds DNA as a homodimer.|||Highest levels in skeletal muscle. Lower levels in heart, liver, kidney, lung and brain. Very low levels in testis and spleen.|||Nucleus|||Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Aldh3b1 ^@ http://purl.uniprot.org/uniprot/Q3TX25|||http://purl.uniprot.org/uniprot/Q80VQ0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Cell membrane|||Dually lipidated in the C-terminus; prenylation occurs prior to, and is a prerequisite for palmitoylation. It is also required for activity towards long-chain substrates.|||Highly expressed in kidney and liver. In brain is expressed at moderate levels in cortex, striatum and hippocampus, and at lower levels in brainstem and cerebellum.|||Oxidizes medium and long chain saturated and unsaturated aldehydes (PubMed:25286108). Metabolizes also benzaldehyde (By similarity). Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde (By similarity). May not metabolize short chain aldehydes. Can use both NADP(+) and NAD(+) as electron acceptor (By similarity). May have a protective role against the cytotoxicity induced by lipid peroxidation (By similarity). http://togogenome.org/gene/10090:Ehd4 ^@ http://purl.uniprot.org/uniprot/Q3TM70|||http://purl.uniprot.org/uniprot/Q9EQP2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP- and membrane-binding protein that probably controls membrane reorganization/tubulation upon ATP hydrolysis. Plays a role in early endosomal transport.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.|||Cell membrane|||Early endosome membrane|||Endosome membrane|||Homooligomer, and heterooligomer with EHD1, EHD2 and EHD3.|||Membrane|||Recycling endosome membrane|||The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins. http://togogenome.org/gene/10090:Cadm4 ^@ http://purl.uniprot.org/uniprot/Q8R464 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nectin family.|||Expressed in the brain and several organs including the kidney and liver.|||Involved in the cell-cell adhesion. Has calcium- and magnesium-independent cell-cell adhesion activity. May have tumor-suppressor activity.|||Membrane|||Monomer and homodimer.|||N-glycosylated. http://togogenome.org/gene/10090:Man1c1 ^@ http://purl.uniprot.org/uniprot/Q6NXK9 ^@ Similarity ^@ Belongs to the glycosyl hydrolase 47 family. http://togogenome.org/gene/10090:Znrf1 ^@ http://purl.uniprot.org/uniprot/Q91V17 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin-protein ligase that plays a role in different processes including cell differentiation, receptor recycling or regulation of inflammation (PubMed:28593998, PubMed:37158982). Mediates the ubiquitination of AKT1 and GLUL, thereby playing a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity. Regulates Schwann cells differentiation by mediating ubiquitination of GLUL (PubMed:20107048). Promotes neurodegeneration by mediating 'Lys-48'-linked polyubiquitination and subsequent degradation of AKT1 in axons: degradation of AKT1 prevents AKT1-mediated phosphorylation of GSK3B, leading to GSK3B activation and phosphorylation of DPYSL2/CRMP2 followed by destabilization of microtubule assembly in axons (PubMed:22057101). Ubiquitinates the Na(+)/K(+) ATPase alpha-1 subunit/ATP1A1 and thereby influences its endocytosis and/or degradation. Controls ligand-induced EGFR signaling via mediating receptor ubiquitination and recruitment of the ESCRT machinery. Acts as a negative feedback mechanism controlling TLR3 trafficking by mediating TLR3 'Lys-63'-linked polyubiquitination to reduce type I IFN production. Modulates inflammation by promoting caveolin-1/CAV1 ubiquitination and degradation to regulate TLR4-activated immune response.|||Endosome|||Interacts with AKT1, GLUL and TUBB2A (PubMed:19737534, PubMed:20107048, PubMed:22057101). Interacts with ZNRF2. Interacts (via its RING domain) with UBE2N. Interacts (when phosphorylated) with YWHAE (By similarity).|||Lysosome|||Membrane|||N-myristoylation targets ZNRF1 to intracellular membranes.|||Phosophorylated by SRC at Tyr-103; leading to 'Lys-63'-linked ubiquitination of TLR3, lysosomal trafficking and degradation.|||The RING-type zinc finger domain is required for E3 ligase activity.|||ZNRF1-deficient mice are more resistant to infection by encephalomyocarditis virus (ECMV) and SARS-CoV-2 with enhanced type I interferon production (PubMed:37158982). However, the display exacerbated lung barrier damage triggered by antiviral immunity, leading to enhanced susceptibility to respiratory bacterial superinfections. Mice are also are more resistant to LPS and CLP-induced sepsis (PubMed:28593998).|||synaptic vesicle membrane http://togogenome.org/gene/10090:Hdgfl2 ^@ http://purl.uniprot.org/uniprot/Q3UMU9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (By similarity). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (By similarity). Involved in cellular growth control, through the regulation of cyclin D1 expression (By similarity). Associates with chromatin (PubMed:22212508).|||Belongs to the HDGF family.|||Binds to condensed chromatin in mitotic cells.|||Binds to non-condensed chromatin in the presence of HDGF.|||Cytoplasm|||Interacts with HDGF.|||Interacts with trimethylated 'Lys-36' of histone H3 (H3K36me3). Interacts with trimethylated 'Lys-79' of histone H3 (H3K79me3), but has higher affinity for H3K36me3 (By similarity). Interacts with IWS1 (By similarity). Interacts with H2AX, POGZ, RBBP8 and CBX1 (By similarity). Interacts with histones H3K9me3, H3K27me3 and H3K36me2 (By similarity). Interacts with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Interacts with SMARCA4/BRG1/BAF190A, in a DPF3a-dependent manner (PubMed:32459350). Interacts with SMARCC1/BAF155 and SMARCD1/BAF60A in a DPF3a-dependent manner (By similarity).|||Mice show severely impaired post-injury muscle regeneration.|||Nucleus|||Selectively interacts with HDGF (N-terminally processed form).|||Ubiquitously expressed. http://togogenome.org/gene/10090:Krt6a ^@ http://purl.uniprot.org/uniprot/P50446 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Epidermis-specific type I keratin involved in wound healing (PubMed:10866680). Involved in the activation of follicular keratinocytes after wounding, while it does not play a major role in keratinocyte proliferation or migration (PubMed:10866680). Participates in the regulation of epithelial migration by inhibiting the activity of SRC during wound repair (PubMed:22529101).|||Heterodimer of a type I and a type II keratin. KRT6 isomers associate with KRT16 and/or KRT17 (PubMed:8636216). Interacts with TCHP (By similarity).|||Predominates in the adult trunk skin, tongue, trachea/esophagus and eye. In adult skin, localization is restricted to hair follicles, where it is localized predominantly in the outer root sheath.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).|||With the exception of specific body sites, expression is induced under conditions of epithelial hyperproliferation such as wound healing, certain skin diseases, cancer, and by treatment of the skin with the phorbol ester PMA. Upon wounding, induced in the outer root sheath and the interfollicular epidermis including the basal cell layer (PubMed:10866680).|||Wound healing defects. Delay in reepithelialization from the hair follicle while the healing of full-thickness skin wounds is not impaired. http://togogenome.org/gene/10090:Hmbox1 ^@ http://purl.uniprot.org/uniprot/H3BKM3|||http://purl.uniprot.org/uniprot/Q8BJA3 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Associates with the telomerase holoenzyme complex. Interacts with DKC1, XRCC6 and COIL.|||Binds directly to 5'-TTAGGG-3' repeats in telomeric DNA (By similarity). Associates with the telomerase complex at sites of active telomere processing and positively regulates telomere elongation (By similarity). Important for TERT binding to chromatin, indicating a role in recruitment of the telomerase complex to telomeres (PubMed:23685356). Also plays a role in the alternative lengthening of telomeres (ALT) pathway in telomerase-negative cells where it promotes formation and/or maintenance of ALT-associated promyelocytic leukemia bodies (APBs) (By similarity). Enhances formation of telomere C-circles in ALT cells, suggesting a possible role in telomere recombination (By similarity). Might also be involved in the DNA damage response at telomeres (By similarity).|||Cajal body|||Cytoplasm|||Nucleus|||PML body|||Reported to have transcriptional repression activity in vitro. However, it is unclear whether this protein has any function in transcription in vivo.|||The homeobox domain is required for binding to 5'-TTAGGG-3' repeats in telomeres, and for telomere localization.|||telomere http://togogenome.org/gene/10090:Slc38a11 ^@ http://purl.uniprot.org/uniprot/Q3USY0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Membrane|||Putative sodium-dependent amino acid/proton antiporter. http://togogenome.org/gene/10090:Kmt2d ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ73 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Hhipl1 ^@ http://purl.uniprot.org/uniprot/Q14DK5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the HHIP family.|||Secreted http://togogenome.org/gene/10090:Atp6v0a2 ^@ http://purl.uniprot.org/uniprot/P15920 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase 116 kDa subunit family.|||Cell membrane|||Endosome membrane|||Relatively high expression in kidney and liver. Lower levels in the spleen, testis, and skeletal muscle. Also expressed in the thymus.|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Essential component of the endosomal pH-sensing machinery (PubMed:16415858). May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH (By similarity). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Directly interacts with PSCD2 through its N-terminal cytosolic tail in an intra-endosomal acidification-dependent manner (PubMed:16415858). Disruption of this interaction results in the inhibition of endocytosis (PubMed:16415858). Interacts with SPAAR (By similarity). http://togogenome.org/gene/10090:Ndufa12 ^@ http://purl.uniprot.org/uniprot/A0A0R4J275|||http://purl.uniprot.org/uniprot/Q7TMF3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA12 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lypd8 ^@ http://purl.uniprot.org/uniprot/Q9D7S0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CNF-like-inhibitor family.|||Cell membrane|||GPI-anchored. The GPI-anchor is cleaved, leading to secretion into the colonic lumen.|||Highly N-glycosylated. Not O-glycosylated.|||Mice are highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS), due to the presence of bacteria in the inner mucus layer. Mice are healthy when raised in a specific-pathogen-free environment, in which bacterial contamination was strictly controlled.|||Secreted|||Secreted protein specifically required to prevent invasion of Gram-negative bacteria in the inner mucus layer of the colon epithelium, a portion of the large intestine which is free of commensal microbiota. Prevents invasion of flagellated microbiota by binding to the flagellum of bacteria, such as P.mirabilis, thereby inhibiting bacterial motility in the intestinal lumen. Segregation of intestinal bacteria and epithelial cells in the colon is required to preserve intestinal homeostasis.|||Specifically present in enterocytes located at the uppermost epithelial layer of the colon (at protein level). Exclusively expressed in the large intestine: specifically expressed on the apical surface of epithelial cells located at the uppermost layer of the colonic gland. http://togogenome.org/gene/10090:Ssu72 ^@ http://purl.uniprot.org/uniprot/Q9CY97 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, low level expression detected throughout the embryo with relative accumulation in spinal cord and brain folds. At 13.5 dpc, highly expressed in the CNS both in the ventricular (mitotic) and marginal (post mitotic) zones, in the PNS in dorsal root and trigeminal ganglia, and the developing gut. During development, expression in the central nervous system and peripheral nervous system persists, and expression in the intestine is further induced. Expression in the intestine is observed throughout the mucosal villi, which contains epithelial cells and other cell types. High expression is also detected in the lens. No expression is seen in other tissues such as liver, lung, bone, cardiac and skeletal muscles.|||Belongs to the SSU72 phosphatase family.|||Cytoplasm|||Highly expressed in the brain. Expressed at low level in most tissues.|||Interacts with GTF2B (via C-terminus); this interaction is inhibited by SYMPK. Interacts with RB1. Interacts with CD226. Interacts with SYMPK.|||Nucleus|||Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination. Plays a role in pre-mRNA polyadenylation via its interaction with SYMPK. http://togogenome.org/gene/10090:Skic2 ^@ http://purl.uniprot.org/uniprot/Q6NZR5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. SKI2 subfamily.|||Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8. Interacts with HBS1L isoform 2.|||Cytoplasm|||Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways. The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation. SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling. In the nucleus, the SKI complex associates with transcriptionally active genes in a manner dependent on PAF1 complex (PAF1C).|||Nucleus http://togogenome.org/gene/10090:Disc1 ^@ http://purl.uniprot.org/uniprot/Q811T9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in granule cell precursors within the dentate migratory stream during the first week of postnatal life and in differentiated granule cells of the hippocampus (at protein level). Detected in heart, brain, kidney, and testis (PubMed:12504857). Expressed in dentate gyrus, hippocampus and in the olfactory bulb.|||Expressed in neuronal progenitors residing in the ventricular and subventriculare zones and in postmitotic neurons in the cortical plate of the cerebral cortex at 15 dpc. Expressed in granule cell precursors within the dentate migratory stream of the hippocampus at 19 dpc (at protein level).|||Interacts with NDEL1 (PubMed:14962739). Interacts with CCDC88A (via C-terminus); the interaction is direct (PubMed:19778506). Interacts with GSK3B (PubMed:19303846). Interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 and TRAF3IP1 (By similarity). Interaction with microtubules may be mediated in part by TRAF3IP1. Interacts (via C-terminal) with PCNT (By similarity). Interacts with CHCHD6 (By similarity). Interacts with CCDC141 (PubMed:20956536). Interacts with FBXW7, the substrate-recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex; the interaction targets DISC1 for proteasomal degradation (By similarity). Interacts with ZNF365 (By similarity). Interacts with ATF4; inhibiting ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). Interacts with PDE4B (By similarity).|||Involved in the regulation of multiple aspects of embryonic and adult neurogenesis (PubMed:17825401, PubMed:19502360, PubMed:31444471). Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus (PubMed:17825401, PubMed:19502360). Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance (PubMed:19303846). Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation (PubMed:19778506). Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A (PubMed:19778506). Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development (PubMed:19502360). Inhibits ATF4 transcription factor activity in neurons by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471). Plays a role, together with PCNT, in the microtubule network formation (By similarity).|||Loss of function of DISC1 in the dentate gyrus of adult mice results in reduced neural progenitor cell proliferation and the appearance of schizophrenic and depressive-like behaviors.|||Mitochondrion|||Postsynaptic density|||Ubiquitinated. Ubiquitination with 'Lys-48'-linked polyubiquitin chains leads to its proteasomal degradation.|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Scgb1b10 ^@ http://purl.uniprot.org/uniprot/A0A087WPW0 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Gdf7 ^@ http://purl.uniprot.org/uniprot/P43029 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Homodimer; disulfide-linked.|||Secreted http://togogenome.org/gene/10090:Ptgr1 ^@ http://purl.uniprot.org/uniprot/Q91YR9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NADP-dependent oxidoreductase L4BD family.|||Cytoplasm|||Monomer or homodimer.|||NAD(P)H-dependent oxidoreductase involved in metabolic inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins (PG), leukotrienes (LT) and lipoxins (LX). Catalyzes with high efficiency the reduction of the 13,14 double bond of 15-oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-oxo-PGF2-alpha (By similarity). Catalyzes with lower efficiency the oxidation of the hydroxyl group at C12 of LTB4 and its derivatives, converting them into biologically less active 12-oxo-LTB4 metabolites (By similarity). Reduces 15-oxo-LXA4 to 13,14 dihydro-15-oxo-LXA4, enhancing neutrophil recruitment at the inflammatory site (By similarity). Plays a role in metabolic detoxification of alkenals and ketones. Reduces alpha,beta-unsaturated alkenals and ketones, particularly those with medium-chain length, showing highest affinity toward (2E)-decenal and (3E)-3-nonen-2-one (By similarity). May inactivate 4-hydroxy-2-nonenal, a cytotoxic lipid constituent of oxidized low-density lipoprotein particles (By similarity). http://togogenome.org/gene/10090:Clca3b ^@ http://purl.uniprot.org/uniprot/E9PUL3|||http://purl.uniprot.org/uniprot/Q91ZF5 ^@ Similarity ^@ Belongs to the CLCR family. http://togogenome.org/gene/10090:Malrd1 ^@ http://purl.uniprot.org/uniprot/A2AJX4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic vesicle membrane|||Enhances production and/or transport of FGF15 and thus has a role in regulation of bile acid synthesis.|||Interacts with FGF15.|||Strongly expressed in epithelial cells of the small intestine. Also detected in kidney cortex, and testis.|||Viable, with enhanced resistance to diet-induced hypercholesterolemia and atherosclerosis (PubMed:10744778). Increased bile acid levels in blood, liver and gastrointestinal tract, associated with significantly reduced levels of FGF15 in the ileum (PubMed:23747249). http://togogenome.org/gene/10090:Sbf1 ^@ http://purl.uniprot.org/uniprot/Q6ZPE2 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an adapter for the phosphatase MTMR2 to regulate MTMR2 catalytic activity and subcellular location. May function as a guanine nucleotide exchange factor (GEF) activating RAB28. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Inhibits myoblast differentiation in vitro and induces oncogenic transformation in fibroblasts.|||Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 1422 in the dsPTPase catalytic loop and does not have phosphatase activity (By similarity). The pocket is however sufficiently preserved to bind phosphorylated substrates, and maybe protect them from phosphatases.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Heterodimer with lipid phosphatase MTMR2. Interacts with KMT2A/MLL1 (via SET domain). Interacts with SUV39H1.|||The C-terminal domain mediates interaction with MTMR2.|||perinuclear region http://togogenome.org/gene/10090:Kctd21 ^@ http://purl.uniprot.org/uniprot/Q3URF8 ^@ Function|||Subunit|||Tissue Specificity ^@ Highly expressed in cerebellum and brain. Expressed in adult cerebellum (at protein level).|||Homopentamer. Interacts with KCTD11; KCTD21 and KCTD11 may associate in pentameric assemblies. Interacts (via BTB domain) with CUL3; indicative for a participation in a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex (PubMed:21472142).|||Probable substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes the ubiquitination of HDAC1. Can function as antagonist of the Hedgehog pathway by affecting the nuclear transfer of transcription factor GLI1; the function probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. Inhibits cell growth and tumorigenicity of medulloblastoma (MDB). http://togogenome.org/gene/10090:ND5 ^@ http://purl.uniprot.org/uniprot/P03921|||http://purl.uniprot.org/uniprot/Q9MD82 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 5 family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ubl7 ^@ http://purl.uniprot.org/uniprot/Q91W67 ^@ Function|||PTM|||Subunit ^@ Binds ubiquitin. Interacts with MAVS; this interaction enhances TRIM21-dependent 'Lys-27'-linked polyubiquitination of MAVS.|||Deubiquitinated by OTUD4 which stabilizes UBL7 expression.|||Interferon-stimulated protein that positively regulates RNA virus-triggered innate immune signaling. Mechanistically, promotes 'Lys-27'-linked polyubiquitination of MAVS through TRIM21 leading to enhanced the IFN signaling pathway. http://togogenome.org/gene/10090:Vmn1r4 ^@ http://purl.uniprot.org/uniprot/Q8R2D3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Surf2 ^@ http://purl.uniprot.org/uniprot/P09926 ^@ Similarity ^@ Belongs to the SURF2 family. http://togogenome.org/gene/10090:Slc22a21 ^@ http://purl.uniprot.org/uniprot/A2RSK7|||http://purl.uniprot.org/uniprot/Q9WTN6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Peroxisome membrane|||Predominantly expressed in testis.|||Sodium-ion independent, medium affinity carnitine transporter. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 746. http://togogenome.org/gene/10090:Copz1 ^@ http://purl.uniprot.org/uniprot/P61924|||http://purl.uniprot.org/uniprot/Q542M2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adaptor complexes small subunit family.|||COPI-coated vesicle membrane|||Cytoplasm|||Golgi apparatus membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins (By similarity). The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex (By similarity).|||The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex. http://togogenome.org/gene/10090:Nhlrc1 ^@ http://purl.uniprot.org/uniprot/Q8BR37 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway.|||Endoplasmic reticulum|||Interacts with AGL. Interacts (via the NHL repeats) with EPM2A/laforin (By similarity). Forms a complex with EPM2A/laforin and HSP70. Interacts with PRDM8 (By similarity).|||Nucleus|||Significant impairment of motor activity, coordination and balance; spontaneous myoclonic seizures; and decreases in episodic memory. 3- and 6-month old mice contain numerous large insoluble aggregates composed mainly of polyglucosans called Lafora bodies (LBs) in skeletal muscle, liver, heart and brain. Glycogen levels are increased 1.6-fold and 1.2-fold respectively in skeletal muscle and liver of 6-month old mice. Glycogen phosphate levels are increased 1.5-fold in skeletal muscle and liver of 6-month old mice. In brain extracts from 1-, 3- and 12-month old mice, total amounts of Epm2b/laforin protein (but not mRNA) are increased. In brain and embryonic fibroblast cells, levels of the autophagy marker Map1lc3b/LC3-II are reduced. In the brain, levels of the autophagy dysfunction marker Sqstm1/p62 are increased.|||The RING domain is essential for ubiquitin E3 ligase activity. http://togogenome.org/gene/10090:Cyb5d2 ^@ http://purl.uniprot.org/uniprot/Q5SSH8 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in the developing brain, in subventricular and ventricular zones of the cerebrum, where neural stem cells and neural precursor cells primarily exist. Expression levels gradually increase during brain development, between 14.5 dpc and P49.|||Belongs to the cytochrome b5 family. MAPR subfamily.|||Expressed in various tissues including brain, heart, adrenal gland, and kidney. In the brain, mainly expressed in pyramidal cells around the CA3 region of Ammon horn in hippocampus. Present in brain (at protein level).|||Heme-binding protein which promotes neuronal but not astrocyte differentiation.|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Probable cloning artifact.|||Secreted|||The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 73 and 106. http://togogenome.org/gene/10090:Nkg7 ^@ http://purl.uniprot.org/uniprot/Q9CY55 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family.|||Membrane http://togogenome.org/gene/10090:Gm21617 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Cdh19 ^@ http://purl.uniprot.org/uniprot/E9Q3A7 ^@ Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Padi3 ^@ http://purl.uniprot.org/uniprot/Q5DTJ8|||http://purl.uniprot.org/uniprot/Q9Z184 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein arginine deiminase family.|||Catalyzes the deimination of arginine residues of proteins.|||Cytoplasm|||Epidermis and hair follicles.|||No visible phenotype. The skin of 7-week-old null mice appeared normal, but scanning electron microscopy revealed structural alterations in the whiskers and hair coat morphology (PubMed:27866708). http://togogenome.org/gene/10090:Pcna ^@ http://purl.uniprot.org/uniprot/P17918|||http://purl.uniprot.org/uniprot/Q542J9 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by CREBBP and p300/EP300; preferentially acetylated by CREBBP on Lys-80, Lys-13 and Lys-14 and on Lys-77 by p300/EP300 upon loading on chromatin in response to UV irradiation. Lysine acetylation disrupts association with chromatin, hence promoting PCNA ubiquitination and proteasomal degradation in response to UV damage in a CREBBP- and EP300-dependent manner. Acetylation disrupts interaction with NUDT15 and promotes degradation (By similarity).|||Auxiliary protein of DNA polymerase delta and epsilon, is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion (By similarity).|||Belongs to the PCNA family.|||Homotrimer. Interacts with p300/EP300; the interaction occurs on chromatin in UV-irradiated damaged cells. Interacts with CREBBP (via transactivation domain and C-terminus); the interaction occurs on chromatin in UV-irradiated damaged cells. Directly interacts with POLD1, POLD3 and POLD4 subunits of the DNA polymerase delta complex, POLD3 being the major interacting partner; the interaction with POLD3 is inhibited by CDKN1A/p21(CIP1). Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with EXO1, POLH, POLK, DNMT1, ERCC5, FEN1, CDC6 and POLDIP2 (By similarity). Interacts with POLB (By similarity). Interacts with APEX2; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA (PubMed:12573260). Forms a ternary complex with DNTTIP2 and core histone (By similarity). Interacts with KCTD10 (By similarity). Interacts with PPP1R15A (PubMed:9371605). Interacts with SMARCA5/SNF2H (By similarity). Interacts with BAZ1B/WSTF; the interaction is direct and is required for BAZ1B/WSTF binding to replication foci during S phase (By similarity). Interacts with HLTF and SHPRH. Interacts with NUDT15; this interaction is disrupted in response to UV irradiation and acetylation. Interacts with CDKN1A/p21(CIP1) and CDT1; interacts via their PIP-box which also recruits the DCX(DTL) complex. The interaction with CDKN1A inhibits POLD3 binding. Interacts with DDX11. Interacts with EGFR; positively regulates PCNA. Interacts with PARPBP. Interacts (when ubiquitinated) with SPRTN; leading to enhance RAD18-mediated PCNA ubiquitination. Interacts (when polyubiquitinated) with ZRANB3. Interacts with SMARCAD1. Interacts with CDKN1C. Interacts with PCLAF (via PIP-box) (By similarity). Interacts with RTEL1 (via PIP-box); the interaction is direct and essential for the suppression of telomere fragility (PubMed:24115439). Interacts with FAM111A (via PIP-box); the interaction is direct and required for PCNA loading on chromatin binding. Interacts with LIG1. Interacts with SETMAR. Interacts with ANKRD17. Interacts with FBXO18/FBH1 (via PIP-box); the interaction recruits the DCX(DTL) complex and promotes ubiquitination and degradation of FBXO18/FBH1. Interacts with POLN (By similarity). Interacts with SDE2 (via PIP-box); the interaction is direct and prevents ultraviolet light induced monoubiquitination (By similarity). Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR; interaction at least with PCNA occurs during DNA replication (By similarity). Interacts with MAPK15; the interaction is chromatin binding dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2. Interacts with PARP10 (via PIP-box) (By similarity). Interacts with DDI2 (By similarity). Interacts with HMCES (via PIP-box) (By similarity). Interacts with TRAIP (via PIP-box) (By similarity). Interacts with UHRF2 (By similarity). Interacts with ALKBH2; this interaction is enhanced during the S-phase of the cell cycle. Interacts with ATAD5; the interaction promotes USP1-mediated PCNA deubiquitination (By similarity).|||Induced in IL2-stimulated proliferating T-lymphocytes.|||Methylated on glutamate residues by ARMT1.|||Nucleus|||Phosphorylated. Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA (By similarity).|||This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand.|||Ubiquitinated. Following DNA damage, can be either monoubiquitinated to stimulate direct bypass of DNA lesions by specialized DNA polymerases or polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Following induction of replication stress, monoubiquitinated by the UBE2B-RAD18 complex on Lys-164, leading to recruit translesion (TLS) polymerases, which are able to synthesize across DNA lesions in a potentially error-prone manner. An error-free pathway also exists and requires non-canonical polyubiquitination on Lys-164 through 'Lys-63' linkage of ubiquitin moieties by the E2 complex UBE2N-UBE2V2 and the E3 ligases, HLTF, RNF8 and SHPRH. This error-free pathway, also known as template switching, employs recombination mechanisms to synthesize across the lesion, using as a template the undamaged, newly synthesized strand of the sister chromatid. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis. Sumoylated during S phase (By similarity). http://togogenome.org/gene/10090:Syt2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J2C2|||http://purl.uniprot.org/uniprot/P46097 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Binding to BoNT/B induces formation of an alpha-helix in the membrane-proximal extracytoplasmic domain (PubMed:17167418, PubMed:23807078).|||(Microbial infection) Interacts with C.botulinum neurotoxin type B (BoNT/B, botB).|||(Microbial infection) Interacts with C.botulinum neurotoxin type G (BoNT/G, botG).|||(Microbial infection) Receptor for C.botulinum neurotoxin type B (BoNT/B, botB); interaction is improved in the presence of gangliosides (PubMed:14504267). The toxin binds via the vesicular domain (residues 47-60) (PubMed:14504267, PubMed:17167418, PubMed:23807078).|||(Microbial infection) Receptor for C.botulinum neurotoxin type G (BoNT/G, botG); gangliosides are not required for (or only very slightly improve) binding to a membrane-anchored receptor fragment (PubMed:20219474). The toxin binds via the vesicular domain (residues 47-55) (PubMed:20219474).|||Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.|||Cytoplasm|||Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties (PubMed:7961887). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (PubMed:7961887). Plays a role in dendrite formation by melanocytes (By similarity).|||Homotetramer (Probable). Heterodimer; heterodimerizes with SYT1 in presence of calcium (By similarity). Interacts with SCAMP5 (By similarity). Interacts with STON2 (By similarity). Interacts with PRRT2 (PubMed:27052163).|||May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone.|||Phosphorylation at Thr-202 by WNK1, changes the calcium requirement for SYT2-binding to phospholipid membranes.|||The first C2 domain mediates Ca(2+)-dependent phospholipid binding (PubMed:7961887).|||The second C2 domain mediates interaction with Stonin 2. The second C2 domain mediates phospholipid and inositol polyphosphate binding in a calcium-independent manner (PubMed:7961887).|||chromaffin granule membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Osgin1 ^@ http://purl.uniprot.org/uniprot/Q8VC10 ^@ Function|||Similarity ^@ Belongs to the OKL38 family.|||Regulates the differentiation and proliferation through the regulation of cell death. http://togogenome.org/gene/10090:Ncapd3 ^@ http://purl.uniprot.org/uniprot/K4DI67|||http://purl.uniprot.org/uniprot/Q3UTU7|||http://purl.uniprot.org/uniprot/Q6ZQK0|||http://purl.uniprot.org/uniprot/Q80W41 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the condensin-2 complex, which contains the SMC2 and SMC4 heterodimer, and 3 non SMC subunits that probably regulate the complex: NCAPH2, NCAPD3 and NCAPG2.|||Component of the condensin-2 complex.|||Nucleus|||Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis.|||Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis. May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Specifically required for decatenation of centromeric ultrafine DNA bridges during anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size. http://togogenome.org/gene/10090:Ndufa11 ^@ http://purl.uniprot.org/uniprot/G5E814 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA11 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Aco1 ^@ http://purl.uniprot.org/uniprot/P28271 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aconitase/IPM isomerase family.|||Bifunctional iron sensor that switches between 2 activities depending on iron availability (By similarity). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization. Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA (PubMed:1956798).|||Binds 1 [4Fe-4S] cluster per subunit.|||Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.|||Interacts (when associated with the 4Fe-4S) with FBXL5. Interacts with frataxin(81-210).|||cytosol http://togogenome.org/gene/10090:Psmc2 ^@ http://purl.uniprot.org/uniprot/P46471|||http://purl.uniprot.org/uniprot/Q8BVQ9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC2 and few additional components. Interacts with NDC80 and SQSTM1. Interacts with PAAF1. Interacts with TRIM5.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC2 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.|||Cytoplasm|||Monoubiquitinated by RNF181.|||Phosphorylated. Dephosphorylated by UBLCP1 which impairs PSMC2 ATPase activity and disrupts 26S proteasome assembly. http://togogenome.org/gene/10090:Haus2 ^@ http://purl.uniprot.org/uniprot/Q9CQS9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS2 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||centrosome|||spindle http://togogenome.org/gene/10090:Atp6v1a ^@ http://purl.uniprot.org/uniprot/P50516 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP hydrolysis occurs at the interface between the nucleotide-binding domains of subunits A and B (By similarity). ATP hydrolysis triggers a conformational change in the subunits D and F, which induces a shift of subunit d (By similarity). The c-ring is subsequently rotated and results in a continuous proton translocation across the membrane (By similarity).|||Belongs to the ATPase alpha/beta chains family.|||Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:23863464). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (By similarity). May play a role in neurite development and synaptic connectivity (By similarity).|||Cytoplasm|||Lysosome|||Phosphorylation at Ser-384 by AMPK down-regulates its enzyme activity.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with the V0 complex V-ATPase subunit a4 ATP6V0A4 (PubMed:11495928). Interacts with WFS1 (By similarity). Interacts with alpha-crystallin B chain/CRYAB and with MTOR, forming a ternary complex (PubMed:31786107).|||clathrin-coated vesicle membrane|||cytosol|||secretory vesicle http://togogenome.org/gene/10090:Or56b2 ^@ http://purl.uniprot.org/uniprot/Q99NH4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4c117 ^@ http://purl.uniprot.org/uniprot/Q7TR02 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r56 ^@ http://purl.uniprot.org/uniprot/E9Q4U5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mc3r ^@ http://purl.uniprot.org/uniprot/P33033|||http://purl.uniprot.org/uniprot/Q544G7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Brain.|||Cell membrane|||Membrane|||Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain (PubMed:19036988). http://togogenome.org/gene/10090:Haus1 ^@ http://purl.uniprot.org/uniprot/Q8BHX1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS1 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Associates with microtubules. The interaction with microtubules is strong during mitosis, while it is weak or absent during interphase. It is unclear whether this interaction is direct or indirect (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||Cytoplasm|||centrosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Man2a2 ^@ http://purl.uniprot.org/uniprot/Q197W7|||http://purl.uniprot.org/uniprot/Q8BRK9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 38 family.|||Binds 1 zinc ion per subunit.|||Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway (By similarity).|||Golgi apparatus membrane|||Homodimer; disulfide-linked (By similarity). Interacts with MGAT4D. http://togogenome.org/gene/10090:Anks4b ^@ http://purl.uniprot.org/uniprot/Q8K3X6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. Plays a role in assembly of the complex (By similarity). May play a role in cellular response to endoplasmic reticulum stress (PubMed:22589549).|||Cochlea, kidney, lung, liver, pancreas, salivary gland and small intestine (at protein level). Expressed in kidney, small intestine, pancreas, liver and colon. Not detected in heart, spleen and brain.|||Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5 (By similarity). Interacts with USH1C; the interaction is direct and is required for ANKS4B localization to the tip of microvilli (PubMed:15461667, PubMed:26812017). Interacts with MYO7B; the interaction is direct (PubMed:26812017). May interact with HSPA5 (PubMed:22589549).|||microvillus http://togogenome.org/gene/10090:Or51e1 ^@ http://purl.uniprot.org/uniprot/Q8VGZ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Otud7b ^@ http://purl.uniprot.org/uniprot/B2RUR8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C64 family.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Deubiquitinase activity is inhibited following interaction with PARK7.|||Interacts with TRAF6. Interacts with PARK7, leading to inhibit deubiquitinase activity. Interacts with EGFR, ITCH and NEDD4 (By similarity). Interacts with TRAF3 (PubMed:23334419). Interacts with ZAP70 in activated T cells, but not in resting T cells (PubMed:26903241).|||Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (PubMed:23334419). Negatively regulates mucosal immunity against infections (PubMed:23334419). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (PubMed:26903241). Mediates deubiquitination of EGFR (By similarity). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains. Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure. Hydrolyzes both linear and branched forms of polyubiquitin (By similarity).|||No visible phenotype in neonates (PubMed:26903241). Mice do not show obvious defects in survival, except a moderately reduced body weight (PubMed:23334419). They however display hyperactivation of non-canonical NF-kappa-B without affecting canonical NF-kappa-B activation. Mice show B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa and elevated host-defense ability against an intestinal bacterial pathogen, Citrobacter rodentium (PubMed:23334419). At 12 months after birth, mutant mice display impaired T cell homeostasis with increased numbers of naive T cells and reduced numbers of Th1 memory-like T cells (PubMed:26903241). Young adults that have no overt change in T cell homeostasis still show impaired production of effector T cells in response to repeated stimulation with an antigen and an impaired defense against infection by L.monocytogenes (PubMed:26903241). Conversely, mutant mice are less susceptible to experimentally induced autoimmune encephalitis (PubMed:26903241).|||Nucleus|||Phosphorylated by EGFR.|||The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate. http://togogenome.org/gene/10090:Or10d3 ^@ http://purl.uniprot.org/uniprot/Q8VEY3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Pdcd5 ^@ http://purl.uniprot.org/uniprot/P56812|||http://purl.uniprot.org/uniprot/Q564F6 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the PDCD5 family.|||May function in the process of apoptosis.|||Widely expressed. http://togogenome.org/gene/10090:Tlcd3b ^@ http://purl.uniprot.org/uniprot/Q7TNV1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Each isoform has a distinct expression pattern. Isoform 1 is highly expressed in brain. Isoform 2 is expressed at low levels, if any, in all analyzed tissues, with slightly higher levels in testis. Isoform 3 is expressed at very high levels in testis and, at lower levels, in white adipose tissue. In epididymal fat, isoform 3 is expressed at higher levels in obese mice compared with lean mice. By contrast, isoform 1 and 2 levels are significantly lower in obese mice compared with lean mice.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Involved in ceramide synthesis. In vitro, isoform 3 stimulates the production of C16-, C18- and C20-ceramides, isoform 1 slightly increases the levels of C18- and C20-ceramides, while isoform 2 exhibits only minimal activity. May interfere with adipogenesis by stimulating ceramide synthesis.|||Knockout mice exhibit a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina compared with wild-type animals (PubMed:33077892). Knockout male mice are fertile (PubMed:33077892).|||Strongly up-regulated by PPARG.|||Up-regulated during adipogenesis. http://togogenome.org/gene/10090:Synrg ^@ http://purl.uniprot.org/uniprot/Q5SV85 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (By similarity). May act by linking the adapter protein complex AP-1 to other proteins (By similarity). Component of clathrin-coated vesicles (By similarity). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (By similarity).|||Self-associates (By similarity). Interacts with GGA1 (via GAE domain) (By similarity). Interacts with GGA2 and GGA3 (By similarity). Interacts with AP1G1 (via GAE domain), a subunit of adapter protein complex AP-1 (By similarity). Interacts with AP1G2 (via GAE domain) a subunit of adapter protein complex AP-1 (By similarity). Component of the aftiphilin/p200/gamma-synergin complex, at least composed of AFTPH/aftiphilin, HEATR5B/p200a and SYNRG/gamma-synergin, which plays a role in the AP1G1/AP-1-mediated trafficking of transferrin from early to recycling endosomes (By similarity). Within the complex interacts with AFTPH/aftiphilin and HEATR5B/p200a; the interactions are direct (By similarity). Interacts (via EH domain) with SCAMP1 (By similarity).|||The DFXDF motifs mediate the interaction with gamma-appendage subunits AP1G1 and AP1G2.|||clathrin-coated vesicle|||cytosol|||perinuclear region|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gm8978 ^@ http://purl.uniprot.org/uniprot/A0A494BBH0 ^@ Similarity ^@ Belongs to the AB hydrolase superfamily. Lipase family. http://togogenome.org/gene/10090:Arl10 ^@ http://purl.uniprot.org/uniprot/Q9QXJ4 ^@ Similarity ^@ Belongs to the small GTPase superfamily. Arf family. http://togogenome.org/gene/10090:Rlbp1 ^@ http://purl.uniprot.org/uniprot/Q9Z275 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with DEGS1; the interaction increases synthesis of chromophore-precursors by DEGS1.|||Retina and pineal gland. Expressed in Mueller cells (at protein level) (PubMed:23143414).|||Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'. http://togogenome.org/gene/10090:Cbx7 ^@ http://purl.uniprot.org/uniprot/Q8VDS3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of a PRC1-like complex (PubMed:22226355). Distinct PRC1-like core complexes are composed of a RING1 subunit (RING1B or RING1A), one of the six PCGF proteins (PCGF1-6), one PHC protein (PHC1-3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8) (PubMed:22226355). The composition of the PRC1 complex may differ between the PRC1 complex in pluripotent embryonic stem cells containing RNF2, CBX7 and PCGF2, and the PRC1 complex in differentiating cells containing RNF2, CBX2, CBX4 and BMI1 (PubMed:22226355). Interacts with RING1 (PubMed:14647293). Interacts with RNF2, PHC1 and PCGF2 (PubMed:22226355). Interacts (via chromodomain) with histone H3K9Me3 and H3K27me3 (PubMed:16537902). Interacts with H3K9Me2 and H4K20Me1 (PubMed:16537902). Interacts (via chromodomain) with single-stranded and double-stranded RNA; RNA binding seems to be required for the localization to chromatin (PubMed:16537902). Interacts with PCGF1, PCGF3, PCGF5 and PCGF6 (By similarity).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:16537902, PubMed:22226355). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3) (By similarity). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) or at 'Lys-27' (H3K27me3) (PubMed:16537902, PubMed:22226355). Trimethylation at 'Lys-27' (H3K27me3) is important for chromatin recruitment (PubMed:22226355, PubMed:16537902). May possibly also bind trimethylated lysine residues in other proteins (in vitro) (PubMed:16537902). Binds non-coding, single-stranded RNA and double-stranded RNA (PubMed:20541999, PubMed:16537902). Plays a role in the timely repression of differentiation-specific genes in pluripotent embryonic stem cells to maintain the undifferentiated state (PubMed:22226355). Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity (PubMed:14647293).|||Expressed in embryonic stem cells.|||In embryonic fibroblast cultured in vitro, expression gradually decreases with passage number and totally disappears in senescent cells.|||Nucleus http://togogenome.org/gene/10090:Eif4e2 ^@ http://purl.uniprot.org/uniprot/D3YUV9|||http://purl.uniprot.org/uniprot/D3Z729|||http://purl.uniprot.org/uniprot/G3X9H1|||http://purl.uniprot.org/uniprot/Q0P688|||http://purl.uniprot.org/uniprot/Q8BMB3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic initiation factor 4E family.|||Component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation. In association with GIGYF2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide. GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist.|||Cytoplasm|||ISGylation enhances its cap structure-binding activity and translation-inhibition activity.|||Interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 (PubMed:15153109). Does not interact with eIF4G (EIF4G1, EIF4G2 or EIF4G3) (PubMed:15153109). Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (By similarity). Interacts with GIGYF2 (via the 4EHP-binding motif); the interaction is direct (By similarity). Interacts with EIF4ENIF1/4E-T (via YXXXXLphi motif); increasing affinity for the 7-methylguanosine-containing mRNA cap (By similarity).|||Lethality; mice die just before birth.|||P-body|||Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation (PubMed:15153109). Acts as a repressor of translation initiation (By similarity). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (PubMed:15153109). In P-bodies, component of a complex that promotes miRNA-mediated translational repression (By similarity). Involved in virus-induced host response by mediating miRNA MIR34A-induced translational silencing which controls IFNB1 production by a negative feedback mechanism (By similarity).|||Ubiquitinated by ARIH1. The consequences of ubiquitination are however unclear: according to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest. According to another report ubiquitination leads to its subsequent degradation.|||Widely expressed with highest levels in testis, kidney and liver. http://togogenome.org/gene/10090:Washc5 ^@ http://purl.uniprot.org/uniprot/Q8C2E7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. May be involved in axonal outgrowth. Involved in cellular localization of ADRB2. Involved in cellular trafficking of BLOC-1 complex cargos such as ATP7A and VAMP7 (By similarity). Involved in cytokinesis and following polar body extrusion during oocyte meiotic maturation (PubMed:24998208).|||Belongs to the strumpellin family.|||Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. The WASH core complex associates via WASHC2 with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex. Interacts with VCP, PI4K2A (By similarity).|||Early endosome|||Endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Mbl2 ^@ http://purl.uniprot.org/uniprot/P41317 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Calcium-dependent lectin involved in innate immune defense. Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway. Binds to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells, facilitating their uptake by macrophages (By similarity).|||Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.|||Oligomeric complex of 3 or more homotrimers. Interacts with MASP1 and MASP2 (By similarity). Interacts with MEP1A and MEP1B and may inhibit their catalytic activity (By similarity).|||Secreted|||The coiled-coil domain mediates trimerization. http://togogenome.org/gene/10090:Rnf4 ^@ http://purl.uniprot.org/uniprot/Q9QZS2 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Cytoplasm|||E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation (PubMed:20681948). Regulates the degradation of several proteins including PML and the transcriptional activator PEA3 (By similarity). Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation (By similarity). Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1 (By similarity). Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation (By similarity). Catalyzes ubiquitination of sumoylated PARP1 in response to PARP1 trapping to chromatin, leading to PARP1 removal from chromatin by VCP/p97 (By similarity).|||Expression is detected from embryonic day 7 and continues throughout development and into adulthood.|||Homodimer (via RING-type zinc finger domain) (PubMed:20681948). Interacts with GSC2 (PubMed:10822263). Interacts with AR/the androgen receptor and TBP (By similarity). Interacts with TCF20 (PubMed:10849425). Interacts with PATZ1 (By similarity). Interacts with TRPS1; negatively regulates TRPS1 transcriptional repressor activity (PubMed:12885770). Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6). Interacts with PRDM1/Blimp-1 (By similarity).|||In the embryo, expressed primarily in the developing nervous system with strong expression in the dorsal root ganglia and gonads (PubMed:10822263, PubMed:9479498). Ubiquitously expressed in the adult (PubMed:10822263, PubMed:9479498).|||Nucleus|||PML body|||Sumoylated; conjugated by one or two SUMO1 moieties.|||The RING-type zinc finger domain is required for the ubiquitination of polysumoylated substrates.|||The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate. http://togogenome.org/gene/10090:Dhx36 ^@ http://purl.uniprot.org/uniprot/Q8VHK9 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATPase activity is enhanced in the presence of homomeric poly(U) RNAs, but not by double-stranded DNA (dsDNA), double-stranded RNA (dsRNA) and tRNA.|||Belongs to the DEAD box helicase family. DEAH subfamily.|||Cytoplasm|||Expressed in spermatogonia stem cells and primary spermatocytes (at protein level) (PubMed:25611385). Expressed strongly in testis. Weakly expressed in heart, lung, liver, kidney, small intestine, spleen, lymphe node and thymus (PubMed:25611385).|||Expressed in the embryonic heart at 10.5 and increases from 14.5 to 16.5 dpc, and then gradually decreases until postnal day 7 (PubMed:26489465). Expressed during the testicular development from embryonic day 18.5 to postnatal day 35 (PubMed:25611385).|||Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without dsRNA poly(I:C) ligand stimulation (PubMed:21703541). Interacts (via C-terminus) with TICAM1 (via TIR domain) (PubMed:21703541). Interacts (via C-terminus) with DDX21; this interaction serves as bridges to TICAM1 (PubMed:21703541). Interacts with TERT; this interaction is dependent on the ability of DHX36 to bind to the G-quadruplex RNA (G4-RNA) structure present in the telomerase RNA template component (TERC). Interacts with DKC1; this interaction is dependent on the ability of DHX36 to bind to the G4-RNA structure present in TERC. Interacts with PARN; this interaction stimulates PARN to enhance uPA mRNA decay. Interacts with EXOSC3; this interaction occurs in a RNase-insensitive manner. Interacts with EXOSC10; this interaction occurs in a RNase-insensitive manner. Interacts with ILF3; this interaction occurs in a RNA-dependent manner. Interacts with ELAVL1; this interaction occurs in an RNA-dependent manner. Interacts with DDX5; this interaction occurs in a RNA-dependent manner. Interacts with DDX17; this interaction occurs in a RNA-dependent manner. Interacts with HDAC1; this interaction occurs in a RNA-dependent manner (By similarity) (PubMed:21590736). Interacts with HDAC3; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with HDAC4 (PubMed:21590736). Interacts with AGO1. Interacts with AGO2 (By similarity). Interacts with ERCC6 (By similarity).|||Mice die at around embryonic 7 days post-coitum (dpc). Conditional knockout mice in the hematopoeitic system leads to hemolytic anemia, a reduction in blood platelet and erythroblast development (PubMed:22422825). Cardiac progenitor-cell-specific knockout mice die around 12.5 dpc and lead to abnormal cardiovascular development with a reduction in cardiomyocyte proliferation. Mice display increased NKX2-5 mRNA but decreased NKX2-5 protein levels, respectively, in the heart at 12.5 dpc compared to wild-type mice (PubMed:26489465). Male germ-cell-specific knockout mice lead to testicular hypoplasia development, due to spermatogonia differentiation block, meiosis initiation arrest as early as meiosis I stage and an absence of mature sperm in the epididymis (PubMed:25611385). Mice show several alteration in meiosis-related gene expression such as the differentiating spermatogonia markers KIT/c-kit (PubMed:25611385).|||Mitochondrion|||Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:25611385). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:21703541, PubMed:21590736). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-ADN and G4-RNA) (By similarity). Plays a role in genomic integrity (By similarity). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (By similarity). Plays a role in transcriptional regulation. Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:25611385) (By similarity). Plays a role in post-transcriptional regulation (By similarity). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (By similarity). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (By similarity). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (By similarity). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (By similarity). Binds also to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (By similarity). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (PubMed:21703541). Required for the early embryonic development and hematopoiesis (PubMed:22422825). Involved in the regulation of cardioblast differentiation and proliferation during heart development (PubMed:26489465). Involved in spermatogonia differentiation (PubMed:25611385). May play a role in ossification (PubMed:21590736).|||Nucleus|||Nucleus speckle|||Perikaryon|||Stress granule|||The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are propbably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (By similarity).|||axon|||cytosol|||dendrite|||telomere http://togogenome.org/gene/10090:Or1x2 ^@ http://purl.uniprot.org/uniprot/Q8VFE6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ofd1 ^@ http://purl.uniprot.org/uniprot/Q80Z25 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OFD1 family.|||Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164. Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis. Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation.|||Females die at birth and display severe craniofacial and limb abnormalities associated with disorganization of the brain, reduction of the lungs, defects in the great vessels and cystic kidney. Primary cilia are absent on the luminal surface of glomerular and tubular cells of kidneys. Males die earlier during development of the embryo, display failure of left right axis specification associated with a lack of cilia in the embryonic node.|||Homooligomer. Interacts with LCA5. Interacts with RUVBL1; the interaction is direct and may mediate interaction with the NuA4 histone acetyltransferase complex. Interacts with SDCCAG8; the interaction is direct. Interacts with MAP1LC3B. Interacts with C2CD3; OFD1 may act as a negative regulator of C2CD3. Forms a complex with KIAA0753/OFIP and CEP20/FOR20; the interaction with CEP20 is detected only in the presence of KIAA0753. Interacts with PCM1; this interaction may be mediated by KIAA0753/OFIP (PubMed:26643951). Interacts with TBC1D31; regulates OFD1 activity in cilium assembly (By similarity).|||Nucleus|||Phosphorylated. Phosphorylation at Ser-737, by the cAMP-dependent protein kinase PKA, triggers ubiquitination and proteasomal degradation of OFD1. Also increases its interaction with TBC1D31 and regulates its function in ciliogenesis.|||Ubiquitinated by PJA2, upon phosphorylation at Ser-737 by PKA, leads to the proteasomal degradation of OFD1.|||centriolar satellite|||centriole|||cilium basal body http://togogenome.org/gene/10090:Ppp1r14a ^@ http://purl.uniprot.org/uniprot/Q91VC7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PP1 inhibitor family.|||Cytoplasm|||Inhibitor of PPP1CA. Has over 1000-fold higher inhibitory activity when phosphorylated, creating a molecular switch for regulating the phosphorylation status of PPP1CA substrates and smooth muscle contraction (By similarity). http://togogenome.org/gene/10090:Slc35a5 ^@ http://purl.uniprot.org/uniprot/Q921R7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.|||Golgi apparatus membrane|||It is uncertain whether Met-1 or Met-14 is the initiator.|||Probable UDP-sugar:UMP transmembrane antiporter involved in UDP-alpha-D-glucuronate/UDP-GlcA, UDP-GlcNAc/UDP-N-acetyl-alpha-D-glucosamine and UDP-N-acetyl-alpha-D-galactosamine/UDP-GalNAc transport from the cytosol to the lumen of the Golgi.|||Probably forms homooligomers and heterooligomers with SLC35A1, SLC35A2, SLC35A3 and SLC35A4. http://togogenome.org/gene/10090:Ehmt2 ^@ http://purl.uniprot.org/uniprot/Q9Z148 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.|||Chromosome|||Expressed in the developing limb bud at 11.5 dpc (at protein level).|||Heterodimer; heterodimerizes with EHMT1/GLP (PubMed:15774718, PubMed:16702210). Interacts with GFI1B and WIZ (PubMed:16702210). Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2 (By similarity). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2. Interacts with UHRF1 (PubMed:19056828). Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). Interacts with PRDM9 and CDYL; interaction only takes place when PRDM9 is bound to hotspot DNA (PubMed:27932493). Interacts with SMYD5 (PubMed:28250819). Interacts with MSX1 (via homeobox domain) (PubMed:22629437).|||Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. Recruited to the promoters of target genes through interaction with transcriptional repressor MSX1, leading to the inhibition of myoblast differentiation via transcriptional repression of differentiation factors (PubMed:22629437).|||In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.|||Methylated at Lys-239; automethylated.|||Mice show a higher level of histone H3 with acetylated 'Lys-9' (H3K9ac) and/or methylated 'Lys-4' (H3K4me), display severe developmental defects and die within E9.5-E12.5 stages.|||NG36 and G9a were originally thought to derive from two separate genes.|||Nucleus|||The ANK repeats bind H3K9me1 and H3K9me2.|||The SET domain mediates interaction with WIZ.|||Ubiquitous. http://togogenome.org/gene/10090:Or4a27 ^@ http://purl.uniprot.org/uniprot/Q7TR13 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rc3h1 ^@ http://purl.uniprot.org/uniprot/Q4VGL6 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic granule|||HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence.|||Interacts with DDX6 and EDC4 (PubMed:20639877, PubMed:23583643). Interacts with CCR4-NOT deadenylase complex (PubMed:23663784). Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406).|||Mutant animals are born at Mendelian ratio, but die within 6 hours after birth. They displayed a curly tail and malformations of the caudal spinal column. Lethality can be rescued by changing the genetic background from C57BL/6 to outbred CD1, which allows about 4% of the animals to survive to adulthood. These animals display enlarged spleens with a trend toward increased numbers of eosinophils and monocytic/macrophage populations, dramatic and selective expansion of CD8(+) effector-like T-cells. Splenic follicular organization is normal, and the numbers of CD4(+) T-cell subtypes and B-cells are not significantly altered. No spontaneous germinal center formation, autoantibody production, nor autoimmune tissue damage. Ablation of Rc3h1 gene in the T lineage leads to elevated ICOS levels and expansion of effector CD8(+) T-cells, but not autoimmunity (PubMed:21844204). Mice lacking both Rc3h1 and Rc3h2 genes in CD4(+) T-cells develop lymphadenopathy and splenomegaly with increased spleen weight and cellularity, already at young age. They show a prominent lung pathology with a progressive reduction in the alveolar space concomitant with inflammation. They show an average survival of 130 days. CD4(+) T-cells of these mutants show a pronounced bias toward Th17 differentiation (PubMed:21844204, PubMed:23583643).|||P-body|||Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:23663784, PubMed:25026077, PubMed:18172933). Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (PubMed:26000482). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (PubMed:20412057, PubMed:20639877). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4/Ox40 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation (PubMed:23583642, PubMed:23583643, PubMed:15917799). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (PubMed:25282160). Recognizes and binds mRNAs containing a hexaloop stem-loop motif, called alternative decay element (ADE) (PubMed:27010430). Together with ZC3H12A, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (PubMed:29244194). Able to interact with double-stranded RNA (By similarity). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains. Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (By similarity).|||Proteolytically cleaved after Arg-510 and Arg-579 by MALT1 in activated CD4(+) T cells; cleavage at Arg-510 and Arg-579 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation.|||The RING-type zinc finger may be required for proper localization to stress granules, but not to P-bodies.|||The ROQ region is required for CDE RNA-binding (PubMed:27010430, PubMed:25026077, PubMed:23663784). Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA, both sites are important for mRNA decay (By similarity). ADE RNA-binding involves an extended binding surface on the ROQ region with a number of additional residues compared with the CDE RNA (PubMed:27010430). It may also be involved in localization to stress granules (PubMed:20412057, PubMed:23583642).|||Treatment of C57BL/6 males with ethylnitrosourea led to the identification of the sanroque mouse strain. The causative mutation in sanroque appears to be RC3H1 Arg-199. Homozygous sanroque mice develop high titers of autoantibodies and display excessive numbers of follicular helper T-cells and germinal centers with pattern of pathology consistent with lupus (PubMed:15917799). Sanroque mice reproducibly develop intestinal inflammation in the small intestine but not the colon. Extensive cytokine dysregulation resulting in both over-expression and under-expression of chemotactic cytokines occurs in the ileum, the region most prone to the development of inflammation in sanroque mice (PubMed:23451046). They show up-regulation of expression of at least 15 miRNAs in T cells (PubMed:25697406). The lack of compensation of RC3H1 defects by the RC3H2 paralog in sanroque mice may be due to the fact that the mutated protein may retain its scaffolding position within RNA granules, preventing RC3H2 to access mRNAs to be regulated (PubMed:23583642).|||Widely expressed, with highest levels in lymph node and thymus and slightly lesser amounts in brain, lung, and spleen (at protein level) (PubMed:23583643). Very weak expression in heart, muscle, and kidney (at protein level) (PubMed:23583643). Expressed in CD4(+) helper T-cells (at protein level) (PubMed:29244194, PubMed:15917799, PubMed:23583643). http://togogenome.org/gene/10090:Slc2a1 ^@ http://purl.uniprot.org/uniprot/P17809 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Cell membrane|||Early embryonic lethality.|||Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:17320047, PubMed:35810171). Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses (By similarity). Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative transport of glucose into the brain (By similarity). In association with BSG and NXNL1, promotes retinal cone survival by increasing glucose uptake into photoreceptors (By similarity). Required for mesendoderm differentiation (PubMed:35810171).|||Found in a complex with ADD2, DMTN and SLC2A1. Interacts (via C-terminus cytoplasmic region) with DMTN isoform 2. Interacts with SNX27; the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. Interacts with GIPC (via PDZ domain). Interacts with STOM. Interacts with SGTA (via Gln-rich region) (By similarity). Interacts with isoform 1 of BSG (By similarity). Interacts with SMIM43; the interaction may promote SLC2A1-mediated glucose transport to meet the energy needs of mesendoderm differentiation (PubMed:35810171).|||Levels decline 3-fold between days 7.5 and 12.5 of gestation. At 7.5 dpc, expressed more strongly in extraembryonic tissues than in the embryo proper. Expressed in amnion, chorion, and ectoplacental cone. In the yolk sac, expressed more strongly in the mesoderm layer than the ectoderm. Expression fairly widespread in the embryo at 8.5 dpc, but by 10.5 dpc, expression is down-regulated and observed in the eye and the spinal cord.|||Phosphorylation at Ser-226 by PKC promotes glucose uptake by increasing cell membrane localization.|||Photoreceptor inner segment|||Retina (at protein level).|||The uptake of glucose is inhibited by cytochalasin B. Glucose uptake is increased in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment: TPA-induced glucose uptake requires phosphorylation at Ser-226. http://togogenome.org/gene/10090:Hoxd1 ^@ http://purl.uniprot.org/uniprot/Q01822 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family. Labial subfamily.|||Is first detected at the end of the late streak stage in presumptive lateral and extraembryonic mesoderm. During early neurogenesis, it is detected solely in lateral mesoderm. By late neurogenesis and through mid-gestation, it is found in a restricted region of presumed trunk neural crest and the dermatome.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. http://togogenome.org/gene/10090:Dsc2 ^@ http://purl.uniprot.org/uniprot/P55292 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium may be bound by the cadherin-like repeats.|||Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.|||In all epithelia tested and heart.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Gm13102 ^@ http://purl.uniprot.org/uniprot/Q3ULC4 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Nop53 ^@ http://purl.uniprot.org/uniprot/Q8BK35 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOP53 family.|||Homooligomer. Interacts with PTEN; regulates PTEN phosphorylation and increases its stability (By similarity). Interacts with RPL11; retains RPL11 into the nucleolus (PubMed:21804542). Interacts with CDKN2A/isoform tumor suppressor ARF; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation. Interacts with NPM1; the interaction is direct and competitive with MYC. Interacts with NF2 (via FERM domain); the interaction is direct. Interacts with p53/TP53 (via the oligomerization region); the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of p53/TP53. Interacts with RIGI; may regulate RIGI through USP15-mediated 'Lys-63'-linked deubiquitination. Interacts with UBTF (By similarity).|||Knockout embryos are not able to form viable blastocysts. Transgenic mice lacking the expression of Nop53 in the thymus display a dramatic reduction of the number of thymic cells and of the size of the thymus.|||Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis. In ribosome biogenesis, may also play a role in rRNA transcription (By similarity). Also functions as a nucleolar sensor that regulates the activation of p53/TP53 in response to ribosome biogenesis perturbation, DNA damage and other stress conditions. DNA damage or perturbation of ribosome biogenesis disrupt the interaction between NOP53 and RPL11 allowing RPL11 transport to the nucleoplasm where it can inhibit MDM2 and allow p53/TP53 activation (PubMed:21804542). It may also positively regulate the function of p53/TP53 in cell cycle arrest and apoptosis through direct interaction, preventing its MDM2-dependent ubiquitin-mediated proteasomal degradation. Originally identified as a tumor suppressor, it may also play a role in cell proliferation and apoptosis by positively regulating the stability of PTEN, thereby antagonizing the PI3K-AKT/PKB signaling pathway. May also inhibit cell proliferation and increase apoptosis through its interaction with NF2. May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation. Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex. May also regulate cellular aerobic respiration. In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of RIGI (By similarity).|||Phosphorylated upon DNA damage probably by ATM and DNA-PK; may regulate NOP53 degradation.|||Ubiquitin-mediated proteasomal degradation is regulated by c-JUN. It is associated with relocalization to the nucleoplasm and decreased homooligomerization.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Slc30a10 ^@ http://purl.uniprot.org/uniprot/Q3UVU3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange. Required for intracellular manganese homeostasis, an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. Manganese can also be cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis (PubMed:28461334). Could also have an intracellular zinc ion transporter activity, directly regulating intracellular zinc ion homeostasis and more indirectly various signaling pathway and biological processes (By similarity).|||Cell membrane|||Early endosome membrane|||Forms homodimers. Forms heterodimers and high-molecular weight oligomers with SLC30A3, SLC30A2 and SLC30A4; heterodimerization is mediated by covalent-bound tyrosine residues, occurs probably in a tissue-specific manner and could mediate the intracellular zinc transport activity into early endosomes and recycling endosomes.|||Golgi apparatus membrane|||Homozygous knockout mice lacking Slc30a10 are born at expected Mendelian ratios and do not display overt phenotype until postnatal day 16 to 18 (PubMed:28461334). After weaning they fail to gain weight, are smaller, and die prematurely (PubMed:28461334). Manganese levels are elevated in the tested tissues including brain, liver, blood and thyroid and manganese toxicity induces an hypothyroidism phenotype (PubMed:28461334).|||Recycling endosome membrane|||Specifically expressed in fetal liver and fetal brain. http://togogenome.org/gene/10090:Itgb1 ^@ http://purl.uniprot.org/uniprot/P09055 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin beta chain family.|||Cell junction|||Cell membrane|||Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (PubMed:10634791, PubMed:36812915). Integrin alpha-4/beta-1 is a receptor for VCAM1 and recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7/beta-1 integrin, regulates cell adhesion and laminin matrix deposition (PubMed:12941630). Involved in promoting endothelial cell motility and angiogenesis (PubMed:15181153). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules (PubMed:21768292). May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis (PubMed:18804435). ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (By similarity). ITGA4:ITGB1 and ITGA5:ITGB1 bind to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (By similarity). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (By similarity). ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1 (By similarity). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (By similarity). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (By similarity). Plays an important role in myoblast differentiation and fusion during skeletal myogenesis (By similarity).|||Interacts with seprase FAP (seprase); the interaction occurs at the cell surface of invadopodia membrane in a collagen-dependent manner (By similarity). Heterodimer of an alpha and a beta subunit. Beta-1 associates with either alpha-1, alpha-2, alpha-3, alpha-4, alpha-5, alpha-6, alpha-7, alpha-8, alpha-9, alpha-10, alpha-11 or alpha-V. ITGA6:ITGB1 is found in a complex with CD9; interaction takes place in oocytes and is involved in sperm-egg fusion (PubMed:10634791). Binds LGALS3BP and NMRK2, when associated with alpha-7, but not with alpha-5. Interacts with FLNA, FLNB, FLNC and RANBP9. Interacts with KRT1 in the presence of RACK1 and SRC. Interacts with JAML; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization. Interacts with RAB21. Interacts (via the cytoplasmic region) with RAB25 (via the hypervariable C-terminal region). Interacts with MYO10. Interacts with ITGB1BP1 (via C-terminal region); the interaction is a prerequisite for focal adhesion disassembly. Interacts with TLN1; the interaction is prevented by competitive binding of ITGB1BP1. Interacts with ACAP1; required for ITGB1 recycling. Interacts with ASAP3. Interacts with FERMT2; the interaction is inhibited in presence of ITGB1BP1. Interacts with DAB2. Interacts with FGR and HCK. Isoform 2 interacts with alpha-7A and alpha-7B in adult skeletal muscle. Isoform 2 interacts with alpha-7B in cardiomyocytes of adult heart. Interacts with EMP2; the interaction may be direct or indirect and ITGB1 has a heterodimer form (PubMed:12189152). ITGA5:ITGB1 interacts with CCN3 (By similarity). ITGA4:ITGB1 is found in a ternary complex with CX3CR1 and CX3CL1 (By similarity). ITGA5:ITGB1 interacts with FBN1 (By similarity). ITGA5:ITGB1 interacts with IL1B. Interacts with MDK (PubMed:15466886). ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation (PubMed:15466886). ITGA6:ITGB1 interacts with MDK; this interaction mediates MDK-induced neurite-outgrowth (PubMed:15466886). ITGA5:ITGB1 interacts with ACE2 (By similarity). Interacts with TMEM182 (By similarity). Interacts with LAMB1 (PubMed:34427057). Interacts with tensin TNS3; TNS3 also interacts with PEAK1, thus acting as an adapter molecule to bridge the association of PEAK1 with ITGB1 (PubMed:35687021). Interacts with tensin TNS4; the interaction displaces tensin TNS3 from the ITGB1 cytoplasmic tail and promotes ITGB1 stability (By similarity).|||Isoform 2 displaces isoform 1 in striated muscles.|||Isoform 2 is expressed in skeletal and cardiac muscles only (at protein level). Isoform 1 is very weakly expressed in striated muscles and not detected in adult skeletal muscle fibers and cardiomyocytes.|||Isoform 2 is not detected in proliferating myoblasts, but it appears immediately after myoblast fusion and its amount continues to rise during myotube growth and maturation reaching its highest level at day 9 through day 10, when mature differentiated myotubes appear in cell culture. Isoform 1 expression is down-regulated during myodifferentiation in culture and it is completely displaced by isoform 2 in mature differentiated myotubes.|||Isoform 2 knockout mice are viable and fertile, but male mice display a mild abnormality of cardiac function reflected by an increased expression of atrial natriuretic peptide and beta myosin heavy chain. Muscles do not show any histological or ultrastructural alterations. Replacement of isoform 1 by isoform 2 results in embryonic lethality before 16.5 dpc with a plethora of developmental defects including open neural tube, which is abnormally waved both rostrally and caudally. Some embryos lack part of the hindbrain and in most embryos the first branchial arch is shortened, which in some of the embryos leaves the tongue exposed. Abnormally strong fibronectin staining is seen in the mesenchyme under the open neural tube. Extravasation of red blood cells is evident in various tissues and they are also found in the pericardial cavity. Choroid plexus is virtually absent correlating with the presence of an abnormally smooth head and small brain cavities. At later developmental stages, a striking feature is the lack of a lower jaw and a dysmorphic lower face. These defects are in part caused by the abnormal migration of neuroepithelial cells.|||Melanosome|||Recycling endosome|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site.|||focal adhesion|||invadopodium membrane|||lamellipodium|||ruffle|||ruffle membrane|||sarcolemma http://togogenome.org/gene/10090:Lce1e ^@ http://purl.uniprot.org/uniprot/Q9D139 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Gabpa ^@ http://purl.uniprot.org/uniprot/Q00422 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Heterotetramer of two alpha and two beta subunits.|||Nucleus|||Transcription factor capable of interacting with purine rich repeats (GA repeats). Positively regulates transcription of transcriptional repressor Rhit/Zpf13.|||Ubiquitous. http://togogenome.org/gene/10090:Jup ^@ http://purl.uniprot.org/uniprot/Q02257 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the beta-catenin family.|||Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton.|||Homodimer. Component of an E-cadherin/catenin adhesion complex composed of at least E-cadherin/CDH1 and gamma-catenin/JUP, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Interacts with MUC1. Interacts with CAV1. Interacts with PTPRJ. Interacts with DSG1. Interacts with DSC1 and DSC2. Interacts with PKP2 (By similarity).|||May be phosphorylated by FER.|||Membrane|||The entire ARM repeats region mediates binding to CDH1/E-cadherin. The N-terminus and first three ARM repeats are sufficient for binding to DSG1. The N-terminus and first ARM repeat are sufficient for association with CTNNA1. DSC1 association requires both ends of the ARM repeat region (By similarity).|||adherens junction|||cytoskeleton|||desmosome http://togogenome.org/gene/10090:Tlcd2 ^@ http://purl.uniprot.org/uniprot/Q8VC26 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TLCD family.|||Cell membrane|||Regulates the composition and fluidity of the plasma membrane (By similarity). Inhibits the incorporation of membrane-fluidizing phospholipids containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA) and thereby promotes membrane rigidity (By similarity). Does not appear to have any effect on LCPUFA synthesis (By similarity). http://togogenome.org/gene/10090:Pramel43 ^@ http://purl.uniprot.org/uniprot/A0A0J9YU88 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Acap2 ^@ http://purl.uniprot.org/uniprot/A0A338P6P6|||http://purl.uniprot.org/uniprot/D4AFX6|||http://purl.uniprot.org/uniprot/Q6ZQK5 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endosome membrane|||GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.|||GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).|||GTPase-activating protein for the ADP ribosylation factor family.|||Interacts with RAB35 (GTP-bound form); the interaction is direct and probably recruits ACAP2 to membranes. Interacts with MICALL1; the interaction is indirect through RAB35.|||PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate protein binding to PIP2 or PIP3 containing membranes.|||The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions. http://togogenome.org/gene/10090:Gm5414 ^@ http://purl.uniprot.org/uniprot/Q6IFZ8 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Cdh24 ^@ http://purl.uniprot.org/uniprot/Q6PFX6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Associates with alpha-, beta- and delta-catenins.|||Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Cadherin-24 mediate strong cell-cell adhesion (By similarity).|||Cell membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Zfhx4 ^@ http://purl.uniprot.org/uniprot/E9Q5A7 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pex1 ^@ http://purl.uniprot.org/uniprot/Q5BL07 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling. Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel. Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5.|||Homooligomer; homooligomerizes in the cytosol, interaction with PEX6 promotes dissociation of the homooligomer. Interacts with PEX6; forming the PEX1-PEX6 AAA ATPase complex, which is composed of a heterohexamer formed by a trimer of PEX1-PEX6 dimers. Interacts indirectly with PEX26, via its interaction with PEX6.|||Peroxisome membrane|||The N-terminal domain shows evolutionary conservation with that of VCP, and is able to bind phospholipids with a preference for phosphatidylinositol monophosphates.|||cytosol http://togogenome.org/gene/10090:Or2ag16 ^@ http://purl.uniprot.org/uniprot/Q7TRN4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4k48 ^@ http://purl.uniprot.org/uniprot/Q8VGE6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cacng3 ^@ http://purl.uniprot.org/uniprot/Q9JJV5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Membrane|||Regulates the trafficking to the somatodendritic compartment and gating properties of AMPA-selective glutamate receptors (AMPARs) (PubMed:18341993). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).|||The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma. Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity). Interacts with AP4M1 and GRIA1; associates GRIA1 with the adaptor protein complex 4 (AP-4) to target GRIA1 to the somatodendritic compartment of neurons (PubMed:18341993). http://togogenome.org/gene/10090:Coro1c ^@ http://purl.uniprot.org/uniprot/Q9WUM4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat coronin family.|||Cell membrane|||Detected in skeletal muscle (at protein level) (PubMed:19651142). Detected in fibroblasts (at protein level) (PubMed:27178841). Ubiquitous (PubMed:9778037).|||Endosome membrane|||Homotrimer (By similarity). Binds F-actin (PubMed:22364218). Interacts with RCC2 (PubMed:25074804). Interacts preferentially with nucleotide-free and GDP-bound RAC1 (PubMed:25074804). Interacts with VIM (via head domain) (PubMed:27178841). Interacts with MICAL2; this interaction recruits MICAL2 to the actin filaments (By similarity).|||No visible phenotype (PubMed:27178841). Fibroblasts from mutant mice display a disordered actin cytoskeleton with a reduced width of the actin stress fibers. Likewise, these cells have several microtubule-organizing centers (MTOCs) and a disordered microbutule network (PubMed:27178841).|||Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1 (PubMed:25074804, PubMed:25925950). Increases the presence of activated RAC1 at the leading edge of migrating cells (PubMed:25074804, PubMed:25925950). Required for normal organization of the cytoskeleton, including the actin cytoskeleton, microtubules and the vimentin intermediate filaments (PubMed:27178841). Required for normal cell proliferation, cell migration, and normal formation of lamellipodia (PubMed:27178841). Plays a role in endoplasmic reticulum-associated endosome fission: localizes to endosome membrane tubules and promotes recruitment of TMCC1, leading to recruitment of the endoplasmic reticulum to endosome tubules for fission. Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane (By similarity). Required for normal distribution of mitochondria within cells (PubMed:27178841).|||The C-terminal coiled-coil domain is essential for cortical membrane localization and oligomerization.|||cell cortex|||cytoskeleton|||lamellipodium|||ruffle membrane http://togogenome.org/gene/10090:Ctsj ^@ http://purl.uniprot.org/uniprot/A0A0R4J0V8|||http://purl.uniprot.org/uniprot/Q9R014 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Expressed specifically in placenta.|||Lysosome http://togogenome.org/gene/10090:Atp6v0a4 ^@ http://purl.uniprot.org/uniprot/Q3UP55|||http://purl.uniprot.org/uniprot/Q920R6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the V-ATPase 116 kDa subunit family.|||Essential component of the vacuolar proton pump (V-ATPase), a multimeric enzyme that catalyzes the translocation of protons across the membranes. Required for assembly and activity of the V-ATPase.|||Membrane|||Specifically expressed in kidney, but not in the heart, brain, spleen, lung, liver, muscle, or testis. Distribution within the kidney appears more widespread than that seen in man. High intensity staining at the surface of intercalated cells, with additional expression in the proximal tubule.|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Involved in normal vectorial acid transport into the urine by the kidney (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with the V1 complex V-ATPase subunit A ATP6V1A (PubMed:11498539). Interacts with the V0 complex V-ATPase subunit c ATP6V0C (PubMed:11498539). http://togogenome.org/gene/10090:Defb8 ^@ http://purl.uniprot.org/uniprot/Q91V82 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A synthetic peptide displays antimicrobial activities against S.aureus, P.aeruginosa, E.coli and B.cepacia. The antimicrobial activity against S.aureus, E.coli and B.cepacia is reduced in raised concentration of NaCl, but its action against P.aeruginosa is independent of NaCl concentration.|||Belongs to the beta-defensin family.|||Most highly expressed in testis and heart.|||Secreted http://togogenome.org/gene/10090:Guca1b ^@ http://purl.uniprot.org/uniprot/Q8VBV8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds three calcium ions.|||Cell membrane|||Expressed in rod photoreceptors in the retina (at protein level). Expressed in cone photoreceptor cells (PubMed:9620085).|||Guca1a and Guca1b double knockout mice show an increase in response to light in dark-adapted cone photoreceptors (PubMed:25673692). Dark-adapted cone photoreceptors show a delayed response time and a delayed recovery time in response to light (PubMed:25673692). Guca1a, Guca1b and Rcvrn triple knockout mice show rod photoreceptors have a reduced current decay during light response (PubMed:29435986).|||Photoreceptor inner segment|||Stimulates two retinal guanylyl cyclase (GCs) GUCY2E and GUCY2F when free calcium ions concentration is low, and inhibits GUCY2E and GUCY2F when free calcium ions concentration is elevated (By similarity). This Ca(2+)-sensitive regulation of GCs is a key event in recovery of the dark state of rod photoreceptors following light exposure (By similarity). May be involved in cone photoreceptor response and recovery of response in bright light (PubMed:25673692).|||The N-terminus is blocked.|||photoreceptor outer segment http://togogenome.org/gene/10090:Cyp4a29 ^@ http://purl.uniprot.org/uniprot/A0A087WPC3 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Rmdn3 ^@ http://purl.uniprot.org/uniprot/Q3UJU9 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RMDN family.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Interacts with PTPN2. Interacts with microtubules. Interacts with VAPB. Interacts (via FFAT motif) with MOSPD2 (via MSP domain). Interacts (via phosphorylated FFAT motif) with MOSPD2, VAPA and VAPB.|||Involved in cellular calcium homeostasis regulation (By similarity). May participate in differentiation and apoptosis of keratinocytes. Overexpression induces apoptosis (By similarity).|||Mitochondrion outer membrane|||Nucleus|||Phosphorylation at Thr-160 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB.|||The FFAT motif is required for interaction with MOSPD2. The FFAT motif is involved in the interaction with VAPA and VAPB and its phosphorylation regulates these interactions.|||The transmembrane region is required for mitochondrial localization.|||spindle|||spindle pole http://togogenome.org/gene/10090:Lrtm1 ^@ http://purl.uniprot.org/uniprot/Q8BXQ3 ^@ Caution|||Subcellular Location Annotation ^@ It is uncertain whether Met-1 or Met-13 is the initiator.|||Membrane http://togogenome.org/gene/10090:Bik ^@ http://purl.uniprot.org/uniprot/O70337 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accelerates programmed cell death. Binding to the apoptosis repressors Bcl-X(L), BHRF1 or Bcl-2 suppresses this death-promoting activity.|||Endomembrane system|||Expressed in testis, kidney, liver, lung and heart.|||Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.|||Interacts with RHBDL4/RHBDD1 (By similarity). Interacts with BCL2L10/BCL-B (By similarity).|||Mitochondrion membrane|||Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage is a necessary step prior its degradation by the proteosome-dependent mechanism (By similarity). http://togogenome.org/gene/10090:Med7 ^@ http://purl.uniprot.org/uniprot/Q9CZB6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 7 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Chrac1 ^@ http://purl.uniprot.org/uniprot/Q9JKP8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Forms a complex with DNA polymerase epsilon subunit POLE3 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome remodeling activity of ISWI/SNF2H and ACF1. Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex (By similarity).|||Heterodimer with POLE3; binds to DNA (By similarity). Component of the CHRAC ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H, BAZ1A/ACF1, CHRAC1 and POLE3; the complex preferentially binds DNA through the CHRAC1-POLE3 heterodimer and possesses ATP-dependent nucleosome-remodeling activity (By similarity). Within the complex, the heterodimer with POLE3 interacts with SMARCA5/SNF2H; the interaction is direct and enhances nucleosome sliding activity by the SMARCA5/SNF2H and BAZ1A/ACF1 interaction (By similarity). Within the complex, the heterodimer with POLE3 interacts with BAZ1A/ACF1; the interactions are direct (By similarity).|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Fam161b ^@ http://purl.uniprot.org/uniprot/Q8CB59 ^@ Similarity|||Subunit ^@ Belongs to the FAM161 family.|||Interacts with FAM161A. http://togogenome.org/gene/10090:Stk32a ^@ http://purl.uniprot.org/uniprot/Q8BGW6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cell membrane http://togogenome.org/gene/10090:Polh ^@ http://purl.uniprot.org/uniprot/Q9JJN0 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-Y family.|||Binds 2 Mg(2+). Prefers Mg(2+), but can also use Mn(2+). In vitro, can also utilize other divalent cations such as Ca(2+).|||DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS) (PubMed:10871396). Due to low processivity on both damaged and normal DNA, cooperates with the heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer is further extended by the tetrameric POLZ complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine (By similarity). Particularly important for the repair of UV-induced pyrimidine dimers (PubMed:10871396). Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have any lyase activity, preventing the release of the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity during base excision repair, thereby avoiding high incidence of mutagenesis. Targets POLI to replication foci (By similarity).|||Interacts with REV1 (PubMed:14657033). Interacts with monoubiquitinated PCNA, but not unmodified PCNA (By similarity). Interacts with POLI; this interaction targets POLI to the replication machinery (By similarity). Interacts with PALB2 and BRCA2; the interactions are direct and are required to sustain the recruitment of POLH at blocked replication forks and to stimulate POLH-dependent DNA synthesis on D loop substrates (By similarity). Interacts (via C-terminus) with TRAIP. Interacts with ubiquitin (By similarity). Interacts with POLDIP2.|||Monoubiquitinated by RCHY1/PIRH2. Ubiquitination depends on integrity of the UBZ3-type zinc finger domain and is enhanced by TRAIP. Ubiquitination inhibits the ability of PolH to interact with PCNA and to bypass UV-induced lesions.|||Nucleus|||The UBZ3-type zinc finger domain and the PIP-box mediate the interaction with ubiquitinated PCNA and are both necessary for the enzymatic activity in translesion synthesis.|||The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity.|||The enzyme in complex with the DNA substrate binds a third divalent metal cation. The binding of this third divalent cation, which is coordinated by water molecules and two oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA synthesis.|||Ubiquitous.|||Up-regulated in proliferating cultured fibroblasts. http://togogenome.org/gene/10090:Pex6 ^@ http://purl.uniprot.org/uniprot/Q99LC9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family.|||Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling. Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel. Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5.|||In the teeth, expressed in ameloblasts and odontoblasts (PubMed:26593283). Expressed in the retina, at higher levels in the ganglion cell layer and photoreceptor layer at the joint between the outer and inner segments (PubMed:26593283, PubMed:27302843).|||Interacts with PEX1; forming the PEX1-PEX6 AAA ATPase complex, which is composed of a heterohexamer formed by a trimer of PEX1-PEX6 dimers. Interacts with PEX26; interaction is direct and promotes recruitment to peroxisomal membranes. Interacts with ZFAND6.|||Peroxisome membrane|||cytosol|||photoreceptor outer segment http://togogenome.org/gene/10090:Glmp ^@ http://purl.uniprot.org/uniprot/Q9JHJ3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GLMP family.|||Detected in brain, heart, liver, kidney, lung, intestine, testis and spleen (PubMed:11444019, PubMed:19489740, PubMed:24487409). Expressed at highest levels in kidney cortex (PubMed:11444019, PubMed:19489740). However, another study reports highest expression levels in lung (PubMed:24487409). Expressed in myoblasts with expression increasing during differentiation into myotubes (PubMed:26707125).|||Expressed throughout embryogenesis (PubMed:11444019). After birth, there is a rapid increase in expression within the first week of life, reaching adult levels by week 2 (PubMed:27141234).|||Highly N-glycosylated (PubMed:19489740, PubMed:19349973). N-glycosylation is essential for GLMP stability and for MFSD1 lysosomal localization (PubMed:32959924).|||Interacts (via lumenal domain) with lysosomal protein MFSD1; the interaction starts while both proteins are still in the endoplasmic reticulum and is required for stability and lysosomal localization of MFSD1.|||Lysosome membrane|||Required to protect lysosomal transporter MFSD1 from lysosomal proteolysis and for MFSD1 lysosomal localization.|||Viable and fertile (PubMed:24487409). Significantly reduced levels of Mfsd1 (PubMed:31661432). Splenomegaly (PubMed:24487409, PubMed:26047317). Reduced size of epididymal fat pads (PubMed:26047317). Enlargement of liver and spontaneous development of liver fibrosis which is not present at birth but develops shortly after and reaches a peak at 4 months of age (PubMed:24487409, PubMed:26047317, PubMed:27141234). The liver phenotype is associated with increased expression of markers for inflammatory responses, apoptosis and oxidative stress (PubMed:24487409, PubMed:27141234). Livers show local foci where hepatocytes are lost and liver sinusoidal endothelial cells are replaced by ordinary capillary endothelium (PubMed:31661432). Reduced liver function (PubMed:27141234). Kupffer cells have increased accumulation of iron and lipofuscin (PubMed:24487409). Decreased blood glucose and serum lipids and increased liver triacylglycerol (PubMed:26047317). Altered liver expression of genes involved in metabolism including decreased expression of Acox1, Angptl4, Fabp1, Slc2a2/Glut2, Ppara, Plin2 and Plin5 and increased expression of Apoc3, Cd36, Fasn, Pdk4, Ppard, Pparg, Scd1 and Scd2 (PubMed:26047317). Increased liver expression of Pecam31/Cd31 and Vwf (PubMed:31661432). Increased glucose and fatty acid uptake in hepatocytes and increased glucose oxidation (PubMed:26047317). Increased de novo lipogenesis in hepatocytes (PubMed:26047317). Increased hepatocyte proliferation and oval cell mobilization up to 6 months of age (PubMed:27141234). Increased frequency of liver tumors after 12 months of age (PubMed:27141234). Anemia, thrombocytopenia, and reduced levels of white blood cells (PubMed:27141234). No effect on composition of muscle fibers but myotubes metabolize glucose faster and have a larger pool of intracellular glycogen while oleic acid uptake, storage and oxidation are significantly reduced (PubMed:26707125). Increased myotube expression of Myh2, Myh4 and Scd1 and decreased expression of Cd36, Myh7, Plin2, Ppara, Ppard, Pparg, Pgc1a and Scd2 (PubMed:26707125). http://togogenome.org/gene/10090:Lclat1 ^@ http://purl.uniprot.org/uniprot/B0V2Q7|||http://purl.uniprot.org/uniprot/Q3UN02 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Endoplasmic reticulum membrane|||Exhibits acyl-CoA:lysocardiolipin acyltransferase (ALCAT) activity; catalyzes the reacylation of lyso-cardiolipin to cardiolipin (CL), a key step in CL remodeling (PubMed:15152008). Recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors (PubMed:15152008). Also exhibits 1-acyl-sn-glycerol-3-phosphate acyltransferase activity (AGPAT) activity; converts 1-acyl-sn-glycerol-3- phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3- phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Possesses lysophosphatidylinositol acyltransferase (LPIAT) activity (PubMed:20668164). Possesses lysophosphatidylglycerol acyltransferase (LPGAT) activity (By similarity). Required for establishment of the hematopoietic and endothelial lineages (PubMed:17675553).|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||Widely expressed with highest expression in heart, liver and 12.5 dpc aorta-gonad-mesonephros and lower levels in the 16 dpc fetal liver and adult bone marrow. In bone marrow, highest levels are found in B-cells compared with whole bone marrow, T-cells, erythrocytes, and granulocytes. http://togogenome.org/gene/10090:Arhgef6 ^@ http://purl.uniprot.org/uniprot/F6WMJ3|||http://purl.uniprot.org/uniprot/Q8K4I3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a RAC1 guanine nucleotide exchange factor (GEF).|||Detected in adult heart, spleen, lung, skeletal muscle, kidney and testis. Detected throughout embryogenesis.|||Interacts with PAK kinases through the SH3 domain. Interacts with GIT1. Component of cytoplasmic complexes, which also contain PXN, GIT1 and PAK1. Interacts with BIN2. Identified in a complex with BIN2 and GIT2 (By similarity). Interacts with PARVB.|||lamellipodium http://togogenome.org/gene/10090:Gpatch3 ^@ http://purl.uniprot.org/uniprot/Q8BIY1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with mitochondrial MAVS; the interaction is markedly increased upon viral infection.|||Involved in transcriptional regulation. It is able to activate transcription from CXCR4 promoter and therefore it might control neural crest cell migration involved in ocular and craniofacial development. Is a negative regulator of immune antiviral response, acting via down-regulation of RIG-I-like receptors signaling and inhibition of type I interferon production. The control mechanism involves interaction with mitochondrial MAVS and inhibition of MAVS assembly with downstream proteins implicated in antiviral response, such as TBK1 and TRAF6.|||Nucleus http://togogenome.org/gene/10090:Cox6a1 ^@ http://purl.uniprot.org/uniprot/P43024|||http://purl.uniprot.org/uniprot/Q9DCW5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 6A family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Membrane|||Mice have walking difficulties. Histologic examination shows thinned sciatic nerves and neurogenic muscular changes, including small angular fibers and small group atrophy. Electrophysiologic studies show delayed motor nerve conduction velocities compared to controls. COX activity and ATP contents in liver cells are decreased.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Aadacl2fm2 ^@ http://purl.uniprot.org/uniprot/W4VSP6 ^@ Similarity ^@ Belongs to the 'GDXG' lipolytic enzyme family. http://togogenome.org/gene/10090:Add2 ^@ http://purl.uniprot.org/uniprot/Q8C0Y2|||http://purl.uniprot.org/uniprot/Q9QYB8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldolase class II family. Adducin subfamily.|||Cell membrane|||Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.|||Found in a complex with ADD2, DMTN and SLC2A1. Interacts with SLC2A1 (By similarity). Heterodimer of an alpha and a beta subunit.|||Membrane|||Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to the erythrocyte membrane receptor SLC2A1/GLUT1 and may therefore provide a link between the spectrin cytoskeleton to the plasma membrane. Binds to calmodulin. Calmodulin binds preferentially to the beta subunit (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Myadml2 ^@ http://purl.uniprot.org/uniprot/Q08AU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MAL family.|||Membrane http://togogenome.org/gene/10090:Gpr15lg ^@ http://purl.uniprot.org/uniprot/A0A0B4J1N3 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Gpr15lg deficient mice in an imiquimod-induced psoriasiform dermatitis model develop less intense itch phenotype than wild type 1 day after imiquimod treatment and afterward, and display less severe capillary leakage and less skin hyperplasia after 5-day imiquimod treatment.|||Has antimicrobial activity against Gram-positive bacteria, including Staphylococcus aureus and Actinomyces spec., and Mycoplasma hominis and lentivirus.|||Highly abundant in the testis, colon, eye, and tongue. Detected in the epithelial layer of the colon, but not the small intestine.|||Highly cationic protein that has multiple functions. Acts as a chemotactic factor that mediates lymphocytes recruitment to epithelia through binding and activation of the G-protein coupled receptor GPR15 (PubMed:28900043, PubMed:28936214). May be a tumor suppressor; together with SUSD2 has a growth inhibitory effect on colon cancer cells which includes G1 cell cycle arrest (By similarity). May regulate keratinocyte proliferation. In addition, through activation of Mas-related G protein-coupled receptors (MRGPRs) contributes to pruritogenesis by activating itch-selective sensory neurons and mast cells degranulation (PubMed:35704588).|||Interacts with SUSD2; the interaction is direct.|||Secreted|||Up-regulated by Imiquimod in the skin. http://togogenome.org/gene/10090:Igtp ^@ http://purl.uniprot.org/uniprot/Q9DCE9 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum|||Expression is induced in response to IFNG/IFN-gamma (PubMed:8702776, PubMed:11500431, PubMed:12438372). Expressed in response to Toxoplasma gondii infection (PubMed:12438372).|||Immunity-related GTPase that plays important roles in host resistance to acute infection by protozoan, such as Toxoplasma gondii and Leishmania major (PubMed:10639151, PubMed:11500431, PubMed:12438372, PubMed:16940170, PubMed:18765738). Acts as a dynamin-like protein that binds to intracellular membranes and promotes remodeling and trafficking of those membranes (By similarity). Acts predominantly to restrict acute protozoan infection: expression is required in both hematopoietic and non-hematopoietic cellular compartments and is dependent on Stat1 (PubMed:12438372). Only plays a partial role in the control of latent Toxoplasma infection (PubMed:12438372). Involved in the clearance of acute protozoan infections by regulating autophagy, possibly by promoting the fusion of phagosomes with lysosomes for efficient degradation of vacuoles containing parasites (PubMed:16940170). Probably involved in membrane disruption of parasite-containing vacuoles (PubMed:18765738). In addition to its role in resistance to acute infection by protozoan, also acts as a negative regulator of the integrated stress response (ISR) following coxsackievirus B3 infection (PubMed:21981022). Promotes differentiation of activated CD8(+) T-cells (PubMed:25644000).|||Lipid droplet|||Mice do not show obvious abnormalities, but are more susceptible to infection by Toxoplasma gondii (PubMed:10639151, PubMed:11500431). In contrast, normal clearance of Listeria monocytogenes and cytomegalovirus infections is observed (PubMed:10639151). Macrophages from knockout mice show impaired envelopment of parasites in autophagosome-like vacuoles (PubMed:16940170). Mice lacking both Irgm1 and Igtp/Irgm3 display resistance to Mycobacterium tuberculosis infection compared to Irgm1 mice that are highly susceptible to infection (PubMed:36629440). Mice lacking Irgm1, Irgm2 and Igtp/Irgm3 (panIrgm mice) show resistance against M.tuberculosis one month post-infection; then, panIrgm mice display higher bacterial burden and altered cytokine during late stage of infection, leading to increased mortality (PubMed:36629440). http://togogenome.org/gene/10090:Zc3h4 ^@ http://purl.uniprot.org/uniprot/Q6ZPZ3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the suppressor of sable family.|||Chromosome|||Early embryonic lethality: embryos do not survive beyond bastocyst stage due to defective epiblast and primitive endoderm lineages formation.|||Interacts with WDR82.|||RNA-binding protein that suppresses transcription of long non-coding RNAs (lncRNAs) (PubMed:33767452). LncRNAs are defined as transcripts more than 200 nucleotides that are not translated into protein (PubMed:33767452). Together with WDR82, part of a transcription termination checkpoint that promotes transcription termination of lncRNAs and their subsequent degradation by the exosome (PubMed:33767452). The transcription termination checkpoint is activated by the inefficiently spliced first exon of lncRNAs (PubMed:33767452). http://togogenome.org/gene/10090:Il15ra ^@ http://purl.uniprot.org/uniprot/Q60819 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble form (sIL-15RA) arises from proteolytic shedding of the membrane-anchored receptor (By similarity). It also binds IL15 and thus interferes with IL15 binding to the membrane receptor (By similarity).|||Cell surface|||High-affinity receptor for interleukin-15 (PubMed:17947230). Can signal both in cis and trans where IL15R from one subset of cells presents IL15 to neighboring IL2RG-expressing cells (PubMed:17947230). In neutrophils, binds and activates kinase SYK in response to IL15 stimulation (By similarity). In neutrophils, required for IL15-induced phagocytosis in a SYK-dependent manner (By similarity).|||It was shown that proteolytic cleavage of Il15ra involves ADAM17/TACE; this publication has later been retracted.|||Membrane|||N-glycosylated and O-glycosylated.|||Nucleus membrane|||The interleukin-15 receptor IL15R is a heterotrimer of IL15RA, IL2RB and IL2RG. IL15RA also self-associates (By similarity). Interacts with SYK (By similarity).|||Widely expressed.|||extracellular space http://togogenome.org/gene/10090:Ndufab1 ^@ http://purl.uniprot.org/uniprot/Q569N0|||http://purl.uniprot.org/uniprot/Q9CR21 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acyl carrier protein (ACP) family.|||Carrier of the growing fatty acid chain in fatty acid biosynthesis (By similarity). Accessory and non-catalytic subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), which functions in the transfer of electrons from NADH to the respiratory chain. Accessory protein, of the core iron-sulfur cluster (ISC) assembly complex, that regulates, in association with LYRM4, the stability and the cysteine desulfurase activity of NFS1 and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity).|||Carrier of the growing fatty acid chain in fatty acid biosynthesis.|||Mammalian complex I is composed of 45 different subunits. Interacts with ETFRF1. Identified in a complex composed of MALSU1, MIEF1 upstream open reading frame protein and NDUFAB1; within the trimeric complex, MIEF1 upstream open reading frame protein functions as a bridging scaffold that interacts with MALSU1 on one side, and with NDUFAB1 on the other side. The complex interacts with the mitochondrial large ribosomal subunit. Interacts with alpha-1-microglobulin chain; this interaction is required for the maintenance of mitochondrial redox homeostasis. Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer. Component of the cyteine desulfurase complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes to the stability and cysteine desulfurase activity of NFS1.|||Mitochondrion|||Phosphopantetheinylation at Ser-112 is essential for interactions with LYR motif-containing proteins. http://togogenome.org/gene/10090:Bbs9 ^@ http://purl.uniprot.org/uniprot/Q811G0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with LZTL1; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking.|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. Required for proper BBSome complex assembly and its ciliary localization (By similarity).|||centriolar satellite|||cilium membrane http://togogenome.org/gene/10090:Acrv1 ^@ http://purl.uniprot.org/uniprot/P50289 ^@ PTM|||Tissue Specificity ^@ Testis.|||The N-terminus is blocked. http://togogenome.org/gene/10090:Lims1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J005|||http://purl.uniprot.org/uniprot/A0A5F8MPJ3|||http://purl.uniprot.org/uniprot/E9QP62|||http://purl.uniprot.org/uniprot/Q99JW4|||http://purl.uniprot.org/uniprot/Q9D7B2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors.|||Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Involved in the regulation of cell survival, cell proliferation and cell differentiation.|||Cell membrane|||Interacts with integrin-linked protein kinase 1 (ILK) via the first LIM domain, and in competition with LIMS2. Part of the heterotrimeric IPP complex composed of integrin-linked kinase (ILK), LIMS1 or LIMS2, and PARVA. Interacts with SH3/SH2 adapter NCK2, thereby linking the complex to cell surface receptors (By similarity). Interacts (via LIM zinc-binding 5) with TGFB1I1.|||Part of the heterotrimeric IPP complex composed of integrin-linked kinase (ILK), LIMS1 or LIMS2, and PARVA.|||focal adhesion http://togogenome.org/gene/10090:Atp6v1g3 ^@ http://purl.uniprot.org/uniprot/Q8BMC1 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase G subunit family.|||Kidney.|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR. http://togogenome.org/gene/10090:Haghl ^@ http://purl.uniprot.org/uniprot/D3YZU6|||http://purl.uniprot.org/uniprot/Q9DB32 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||Binds 2 Zn(2+) ions per subunit.|||Hydrolase acting on ester bonds. http://togogenome.org/gene/10090:Pfdn4 ^@ http://purl.uniprot.org/uniprot/E9Q6U4|||http://purl.uniprot.org/uniprot/Q3UWL8|||http://purl.uniprot.org/uniprot/Q6P0X1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the prefoldin subunit beta family.|||Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.|||Heterohexamer of two PFD-alpha type and four PFD-beta type subunits. http://togogenome.org/gene/10090:Gucy2f ^@ http://purl.uniprot.org/uniprot/Q5SDA5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by GUCA1B when free calcium ions concentration is low, and inhibited by GUCA1B when free calcium ions concentration is high (By similarity). Inhibited by RD3 (By similarity).|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Deficient mice exhibit normal retinal morphology. Electroretinography shows slower recovery of rod from intense illumination. GUCY2F and GUCY2E double knockout mice does not show any photoresponse at 4 weeks of age, rods and cones degenerate at about 2 month of age and the intracellular transport of some phototransduction proteins is impaired.|||Homodimer (By similarity). Interacts with RD3; promotes the exit of GUCY2F from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments (PubMed:21078983).|||Membrane|||Photoreceptor outer segment membrane|||Responsible for the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors (By similarity). Plays an essential role in phototransduction, by mediating cGMP replenishment. May also participate in the trafficking of membrane-asociated proteins to the photoreceptor outer segment membrane (PubMed:17255100).|||Retina.|||The protein kinase domain is predicted to be catalytically inactive.|||There are 9 conserved cysteine residues in sensory guanylate cyclases, 6 in the extracellular domain, which may be involved in intra- or interchain disulfide bonds. http://togogenome.org/gene/10090:Cyp2c29 ^@ http://purl.uniprot.org/uniprot/Q3UEF2|||http://purl.uniprot.org/uniprot/Q64458 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that selectively catalyzes the epoxidation of 14,15 double bond of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) forming 14,15-epoxyeicosatrienoic acid (14,15-EET) regioisomer. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in liver as well as in extrahepatic tissues including brain, kidney, lung, heart, and intestine.|||Microsome membrane http://togogenome.org/gene/10090:Cldn18 ^@ http://purl.uniprot.org/uniprot/P56857|||http://purl.uniprot.org/uniprot/Q8BZS5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 100% incidence of chronic gastritis with atypical distribution of cells in the gastric gland, including fewer parietal and chief cells that are replaced by metaplastic cells with dilated gland lumina (PubMed:22079592). Lack of increase in stomach lumen acidification with age (PubMed:22079592). Lack of sensitivity to gastric acidity and an increase in ion permeability of the gastric paracellular barrier (PubMed:22079592). Spasmolytic polypeptide-expressing metaplasia cells are dominant in the stomach in place of well-differentiated parietal cells and chief cells (PubMed:22079592). Abundant inflammatory cells in the submucosal region (PubMed:22079592). Slight decrease in the localization of Cldn18 isoform A1.1 at tight junctions in the gastric superficial mucous epithelial cells (PubMed:22079592). Upper apical layer of tight junctions in the stomach missing resulting in a decrease in tight junction width (PubMed:22079592). Increase in proinflammatory markers Il1a and Tnf/Tnf-a, the chemoattractant Cxcl1/Kc and prostaglandin E2 inflammatory marker Ptgs2/Cox2 in gastric tissue (PubMed:22079592).|||Belongs to the claudin family.|||Cell membrane|||Defective alveolar formation and increased alveolar macrophage counts evident at 6 weeks of age (PubMed:34702961). Increase in C. neoformans fungal burdens in bronchoalveolar lavage fluids (BALF), lung tissue and alveolar space from 1 day post-infection to 14 days post-infection (PubMed:34702961). Increase in multiplication of C. neoformans and poor granulomatous responses in the lung at 14 days post-infection with overall higher infection burdens in the brain and lungs to 28 days post-infection (PubMed:34702961). Increase in neutrophils, alveolar macrophages, inflammatory monocytes, natural killer cells, CD4-positive T-cells, CD8-positive T-cells and natural killer T-cells in BALF 3 days post-C. neoformans infection (PubMed:34702961). Decrease in IFNG in BALF on days 3 and 7 post-infection, similarly a decrease in Il4 and Il13 in BALF on day 14 and in the lungs on day 3 and day 14 post-infection (PubMed:34702961). Decrease in Il17a in BALF on day 7 and in the lungs on day 14 post-infection (PubMed:34702961). Increase in K(+) ion concentration in BALF, with a decrease in pH which persists 7 days post-infection, resulting in the increased replication of C. neoformans (PubMed:34702961).|||Expressed in lung (PubMed:11585919, PubMed:22437732). Expressed in the stomach (PubMed:22079592).|||Expressed in lung.|||Expressed in stomach (PubMed:11585919, PubMed:22079592, PubMed:22437732). Expressed in bone (PubMed:22437732).|||Expressed in stomach.|||Expressed in the lung (at protein level).|||Expressed in the lungs from 19 dpc, expression is increased at birth and at four weeks of age.|||Induced by 17-beta-estradiol in bone marrow stromal cells, osteoblasts and osteoclasts.|||Interacts with TJP2/ZO-2 (PubMed:22437732). Interacts with TJP1/ZO-1 (PubMed:29400695). Interacts with YAP1 (phosphorylated); the interaction sequesters YAP1 away from the nucleus and thereby restricts transcription of YAP1 target genes (PubMed:29400695).|||Involved in alveolar fluid homeostasis via regulation of alveolar epithelial tight junction composition and therefore ion transport and solute permeability, potentially via downstream regulation of the actin cytoskeleton organization and beta-2-adrenergic signaling (PubMed:24588076). Required for lung alveolarization and maintenance of the paracellular alveolar epithelial barrier (PubMed:24787463). Acts to maintain epithelial progenitor cell proliferation and organ size, via regulation of YAP1 localization away from the nucleus and thereby restriction of YAP1 target gene transcription (PubMed:29400695). Acts as a negative regulator of RANKL-induced osteoclast differentiation, potentially via relocation of TJP2/ZO-2 away from the nucleus, subsequently involved in bone resorption in response to calcium deficiency (PubMed:22437732). Mediates the osteoprotective effects of estrogen, potentially via acting downstream of estrogen signaling independently of RANKL signaling pathways (PubMed:23299504).|||Involved in the maintenance of homeostasis of the alveolar microenvironment via regulation of pH and subsequent T-cell activation in the alveolar space, is therefore indirectly involved in limiting C. neoformans infection.|||Lateral cell membrane|||May act as a tumor suppressor, inhibiting the development of AT2 cell-derived lung tumors.|||Membrane|||Parenchymal expansion phenotype and overall lung enlargement evident from 18 days post-conception (dpc), as a result of increased lung cellularity, airspace enlargement and increase in the number of AT2 cells in the lung alveolar compartments (PubMed:29400695). Increase in AT2 cells in S and G2/M phase of the cell cycle with no change in low levels of apoptosis in the lungs (PubMed:29400695). Increase in bronchoalveolar lavage fluid leakage as a result of alveolar epithelial cell injury at P3 and four weeks of age, resulting in an increase in AT2 cells in the lungs by four weeks of age (PubMed:24787463). Increase in expression of Cldn3 and Cldn4 in lungs at P7 (PubMed:24787463). Fixed alveolar permeability defect and dysregulation of genes involved in lung development in lung tissue, including Areg, Shh, Eln, Vegfa, Fgfr4, and Adm from 4 weeks of age (PubMed:24787463). Impaired alveolarization and decreased lung surface area at four weeks of age (PubMed:24787463). Membrane ruffling and splaying is evident at AT1-AT1 cell junctions at 8 weeks of age (PubMed:24787463). Increase in alveolar fluid clearance and lung permeability (PubMed:24588076). Increase in sodium/potassium-transporting ATPase activity in lungs, accompanied by an increase in Atp1b1 subunit expression, and decreases in Atp1a2, Atp1b3 and Atp1b2 subunit expression (PubMed:24588076). Increase in expression of Cldn3 and Cldn4 in lung tissues with a decrease in Ocln and Egr1 expression in lung tissues (PubMed:24588076). Increase in separation distance between Tjp1/Zo-1 in adjacent cells suggesting tight junction separation (PubMed:24588076). Cytoskeleton rearrangements as evidenced by increased F-actin localization to the plasma membrane and perinuclear actin aggregates with projected radial fibers to the plasma membrane (PubMed:24588076). Decrease in sensitivity to lung injury in response to ventilator-induced lung injury (PubMed:24588076). Increased nuclear localization and protein mobility of Yap1 while phosphorylated Yap1 abundance is decreased in AT2 cells, this results in an increase in Yap1-target genes such as Ccnd1, Areg, Cdk6 and Ccn2/Ctgf at two months of age (PubMed:29400695). Enlargement of the stomach due to increase in gastric mucosal thickness from 2 months of age (PubMed:29400695). Enlargement of the duodenum and kidney from 2 months of age (PubMed:29400695). Histological abnormalities in the gastric mucosa including inflammatory infiltrates and a decrease in the number of well-differentiated gastric chief cells and parietal cells (PubMed:22437732). Reduced total body bone mineral content, total body bone mineral density (BMD), cortical bone thickness, vertebra BMD and femur BMD by 20-25% from 4 to 26 weeks of age (PubMed:22437732, PubMed:23299504). Reduced trabecular bone, trabecular thickness and trabecular number decreased by 50%, whereas trabecular spacing is increased by 50% from 4 to 26 weeks of age (PubMed:22437732). Significant increase in osteoclastogenesis, osteoclast number and number of nuclei in osteoclasts on the surface of the trabecular bone of the proximal tibia (PubMed:22437732). Decrease in bone mass density in the femur, lumbar and whole body (PubMed:22437732). Skeletal defects and osteoclast levels were exacerbated significantly by a calcium depleted diet (PubMed:22437732). Reduction in bone volume to total volume ratio and osteoclast surface to bone surface ratio at 14 weeks of age (PubMed:23299504). Protection against ovariectomy-induced loss of total body, femur and lumbar bone mass density (PubMed:23299504). A 68% increase in incidence of tumors in lungs between 18 and 20 months of age, tumors develop after 10 months of age (PubMed:29400695). Tumors are of a AT2 cell-derived lineage, typically adenocarcinomas with associated alveolar mononuclear cells (PubMed:29400695).|||Required for the formation of the gastric paracellular barrier via its role in tight junction formation, thereby involved in the response to gastric acidification.|||tight junction http://togogenome.org/gene/10090:Or4c100 ^@ http://purl.uniprot.org/uniprot/Q7TR16 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mmp1a ^@ http://purl.uniprot.org/uniprot/Q9EPL5 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 4 Ca(2+) ions per subunit.|||Can be activated without removal of the activation peptide.|||Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (By similarity). Able to degrade synthetic peptides and type I and II fibrillar collagen.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix http://togogenome.org/gene/10090:Hjurp ^@ http://purl.uniprot.org/uniprot/Q6PG16 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres. Acts as a specific chaperone for CENPA and is required for the incorporation of newly synthesized CENPA molecules into nucleosomes at replicated centromeres. Prevents CENPA-H4 tetramerization and prevents premature DNA binding by the CENPA-H4 tetramer. Directly binds Holliday junctions.|||Interacts with CENPA (via CATD domain); the interaction is direct and specific for CENPA since it does not interact with H3.1- or H3.3-containing nucleosomes. Heterotrimer composed of HJURP, CENPA and histone H4, where HJURP interacts with the dimer formed by CENPA and histone H4 and prevents tetramerization of CENPA and H4. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Interacts with 14-3-3 family members in a phosphorylation-dependent manner. Interacts with MSH5 and NBN.|||centromere|||nucleolus http://togogenome.org/gene/10090:Glyat ^@ http://purl.uniprot.org/uniprot/Q91XE0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycine N-acyltransferase family.|||Mitochondrial acyltransferase which transfers an acyl group to the N-terminus of glycine and glutamine, although much less efficiently. Can conjugate a multitude of substrates to form a variety of N-acylglycines, thereby detoxify xenobiotics, such as benzoic acid or salicylic acid, and endogenous organic acids, such as isovaleric acid.|||Mitochondrion http://togogenome.org/gene/10090:Bicra ^@ http://purl.uniprot.org/uniprot/F8VPZ9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:29374058). May play a role in BRD4-mediated gene transcription (By similarity).|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, the core BAF subunits, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). Interacts with BRD4; the interaction bridges BRD4 to the GBAF complex (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or4g7 ^@ http://purl.uniprot.org/uniprot/Q7TQY0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrfn5 ^@ http://purl.uniprot.org/uniprot/Q8BXA0 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRFN family.|||Can form heteromeric complexes with LRFN1, LRFN2, LRFN3 and LFRN4 (By similarity). Able to form homomeric complexes across cell junctions, between adjacent cells (By similarity). Does not interact with DLG1, DLG2 or DLG3 (By similarity). Does not interact with DLG4.|||Cell adhesion molecule that mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Promotes neurite outgrowth in hippocampal neurons (By similarity).|||Due to intron retention.|||Expression starts around 11.5-12.5 dpc. At 11.5 dpc, detected in the outer layer of the telencephalic vesicles. This pattern of expression continues until 17.5 dpc with expression in the cortical plate, but not in the inner layer of the cerebral cortex, including subplate, ventricular zone, and subventricular zone. As also detected in the hippocampus, amygdala and widely in diencephalic nuclei.|||Glycosylated.|||Lacks a cytoplasmic PDZ-binding motif, which has been implicated in function of related LRFN proteins.|||Membrane|||Predominantly expressed in the brain, with a weak, but broad expression in the cerebral cortex and diencephalic nuclei. Strongly expressed in both the pyramidal layer and the dentate gyrus of the hippocampus. Also detected in other parts of the central nervous system, including the olfactory bulb, pons, cerebellum, and medulla oblongata, as well as in the peripheral nervous system, such as the ganglia of cranial nerves and the dorsal root ganglion during gestation. http://togogenome.org/gene/10090:Tas2r102 ^@ http://purl.uniprot.org/uniprot/F8VPL4|||http://purl.uniprot.org/uniprot/Q0VFY9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane http://togogenome.org/gene/10090:Pear1 ^@ http://purl.uniprot.org/uniprot/Q8VIK5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MEGF family.|||Cell membrane|||Expressed in thymocytes, bone marrow stromal and osteogenic cells (at protein level). Strongly expressed in kidney and heart. Moderately expressed in lung, spleen, thymus, liver, brain, testis, skin and stomach. Expressed in hematopoietic stem progenitor cells.|||Interacts with SHC2 upon its aggregation-induced tyrosine phosphorylation.|||Phosphorylated on tyrosine residues by SRC. Tyrosine phosphorylation is detected upon platelet aggregation stimulated by collagen, TRAP and thrombin and platelet-platelet contacts but not after platelet activation. Tyrosine phosphorylation enhanced its association with SHC1 and SHC2 (By similarity). Phosphorylated in the intracellular domain on tyrosine residues.|||When overexpressed, reduces the number of both early and late non-adherent myeloid progenitor cells. http://togogenome.org/gene/10090:Slc7a2 ^@ http://purl.uniprot.org/uniprot/P18581 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Affinity of isoform 2 for arginine uptake is 70-fold higher than for isoform 1.|||Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.|||By macrophage activation.|||Cell membrane|||Detected in liver (at protein level) (PubMed:8385111). Highest expression in liver and T-cells. Also expressed in brain and lung.|||Functions as low-affinity, high capacity permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine).|||Functions as permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine); the affinity for its substrates differs between isoforms created by alternative splicing (PubMed:8195186, PubMed:8385111, PubMed:9174363). May play a role in classical or alternative activation of macrophages via its role in arginine transport (PubMed:16670299).|||Functions as permease that mediates the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine). Shows a much higher affinity for L-arginine than isoform 1.|||Intracellular polyamine levels are reduced in hepatocytes. Infection of knockout mice with parasite P.berghei (ANKA strain) sporozoites results in a reduction in the parasite load in the liver compared to wild type mice.|||N-glycosylated. http://togogenome.org/gene/10090:Adgrb3 ^@ http://purl.uniprot.org/uniprot/Q6ZQ96|||http://purl.uniprot.org/uniprot/Q80ZF8|||http://purl.uniprot.org/uniprot/Q8BJ13|||http://purl.uniprot.org/uniprot/Q8K0A3 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Brain-specific expression.|||Cell membrane|||Forms a heterodimer, consisting of a large extracellular region non-covalently linked to a seven-transmembrane moiety. Interacts (via its TSRs) with C1QL1, C1QL2, C1QL3 and C1QL4. Interacts via (C-terminus) with ELMO1 (PubMed:23628982), ELMO2 and ELMO3.|||Limited to the central nervous system (CNS) at all developmental stages. Peaks 1 day after birth.|||Membrane|||Receptor that plays a role in the regulation of synaptogenesis and dendritic spine formation at least partly via interaction with ELMO1 and RAC1 activity (PubMed:23628982). Promotes myoblast fusion through ELMO/DOCK1 (By similarity).|||The endogenous protein is proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit. http://togogenome.org/gene/10090:Nphp1 ^@ http://purl.uniprot.org/uniprot/Q9QY53 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nephrocystin-1 family.|||Cell junction|||Expressed in the retina (at protein level) (PubMed:16885411, PubMed:19208653, PubMed:29899041). Expressed in the testis (at protein level) (PubMed:10665934). Widespread expression, with weak expression in skeletal muscle, kidney, thyroid, ovary, lung, prostate, thymus, uterus, heart, and liver (PubMed:10665934). Lowest levels in brain and spleen (PubMed:10665934).|||Interacts with INVS and NPHP3 (By similarity). Interacts with Crk-associated substrate BCAR1 (PubMed:10739664, PubMed:11493697). Interacts with NPHP4 (By similarity). Interacts with PTK2B/PYK2 and tensin (PubMed:11493697). Interacts with AHI1 and TNK2 (By similarity). Interacts with NPHP4 in a complex containing NPHP1, NPHP4 and RPGRIP1L/NPHP8 (By similarity). Interacts with IQCB1; the interaction likely requires additional interactors (By similarity). Interacts (via SH3 domain) with PKD1 (PubMed:20856870). Interacts with KIF7 (By similarity). Interacts with ANKS3 (PubMed:25671767). Interacts with SPATA7 (PubMed:29899041). Interacts with FLNA (PubMed:12006559).|||Mice are viable without renal manifestations of nephronophthisis (PubMed:18684731). Male mice are infertile with oligoteratozoospermia (PubMed:18684731). Spermatogenesis is blocked at the early stages of spermatid elongation, with degenerating spermatids sloughing off into the lumen (PubMed:18684731). Early elongating spermatids are detached from Sertoli cells and show a failure of sperm head and tail morphogenesis and an abnormal F-actin distribution (PubMed:18684731). Severe retinal degradation with mislocalized rhodopsin, disorganized outer segments, restricted expression of transducin to the inner segment and abnormal intraflagellar transport (IFT) of IFT57 (PubMed:19208653).|||The SH3 domain mediates the stable interaction with Cas and is involved in establishing tight junctions in epithelial cells.|||Together with BCAR1 it may play a role in the control of epithelial cell polarity. Involved in the organization of apical junctions in kidney cells, together with NPHP4 and RPGRIP1L/NPHP8 (PubMed:21565611). Does not seem to be strictly required for ciliogenesis (PubMed:19208653). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling (PubMed:11493697). May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly (PubMed:19208653). Required for normal retina development (PubMed:19208653). In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19 (PubMed:19208653). Involved in spermatogenesis; required for the differentiation of early elongating spermatids into spermatozoa (PubMed:18684731).|||Widespread and uniform expression in whole embryo at all development stages (PubMed:10665934). Expressed in cell stages of the first meiotic division and thereafter (PubMed:10665934). Initially expressed at day 14 with consistent expression thereafter to day 365 (PubMed:18684731).|||adherens junction|||cilium|||cilium axoneme|||tight junction http://togogenome.org/gene/10090:Fbxo27 ^@ http://purl.uniprot.org/uniprot/Q6DIA9 ^@ Function|||Miscellaneous|||Subunit|||Tissue Specificity ^@ Detected in brain, heart and muscle.|||May be due to a competing acceptor splice site.|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with SKP1 and CUL1 (By similarity).|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Able to recognize and bind complex-type oligosaccharides. http://togogenome.org/gene/10090:Dph5 ^@ http://purl.uniprot.org/uniprot/Q9CWQ0 ^@ Developmental Stage|||Function|||Similarity ^@ Belongs to the diphthine synthase family.|||S-adenosyl-L-methionine-dependent methyltransferase that catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester. The four successive methylation reactions represent the second step of diphthamide biosynthesis.|||The protein is expressed in embryos at 18.5 dpc. http://togogenome.org/gene/10090:Rock1 ^@ http://purl.uniprot.org/uniprot/P70335|||http://purl.uniprot.org/uniprot/Q3UE22 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by RHOA binding. Inhibited by Y-27632 (By similarity).|||Autophosphorylated on serine and threonine residues.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cell membrane|||Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Golgi apparatus membrane|||Highly expressed in brain, heart, lung, liver, stomach, spleen, kidney, testis, muscle, embryo and placenta.|||Homodimer (By similarity). Interacts with RHOA (activated by GTP), RHOB, RHOC, GEM, MYLC2B, RHOE, PPP1R12A, LIMK1, LIMK2, TSG101, CHORDC1, DAPK3, PFN1 and JIP3 (By similarity). Interacts with FHOD1 in a Src-dependent manner (By similarity). Interacts with PTEN. Interacts with ITGB1BP1 (via N-terminus and PTB domain). Interacts with SHROOM3 (PubMed:22493320).|||May be due to a competing donor splice site.|||Mice exhibit both EOB (eyes open at birth) and omphalocele phenotypes as a result of disorganization of actomyosin cables in the eyelid epithelium and defective actin assembly in the umbilical ring.|||Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:19036714, PubMed:19181962). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (PubMed:19036714, PubMed:19181962). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (By similarity). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (PubMed:20008297). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (PubMed:30115939). Promotes keratinocyte terminal differentiation (By similarity). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (PubMed:21768292). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (PubMed:15753128).|||The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated.|||bleb|||centriole|||cytoskeleton|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Wfdc9 ^@ http://purl.uniprot.org/uniprot/Q3UW41 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Oprd1 ^@ http://purl.uniprot.org/uniprot/A2AD37|||http://purl.uniprot.org/uniprot/P32300|||http://purl.uniprot.org/uniprot/Q8BLP9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Brain, with high concentrations in the basal ganglia and limbic regions.|||Cell membrane|||G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.|||May form homooligomers. Forms a heterodimer with OPRM1 (PubMed:18836069). Interacts with GPRASP1 (By similarity). Interacts with RTP4; the interaction promotes cell surface localization of the OPRD1-OPRM1 heterodimer (PubMed:18836069).|||Membrane|||Mice are born at the expected Mendelian rate; they show no obvious phenotype and are fertile. Mutant mice show decreased analgesia in response to opioids, such as deltorphin-2. They do not develop analgesic tolerance to morphine.|||Ubiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4. http://togogenome.org/gene/10090:Creld2 ^@ http://purl.uniprot.org/uniprot/Q9CYA0 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRELD family.|||Endoplasmic reticulum|||Expressed from birth.|||Expressed in chondrocytes (at protein level).|||Interacts with CHRNA4 (By similarity). Component of a complex containing at least CRELD2, MANF, MATN3 and PDIA4 (PubMed:23956175).|||Protein disulfide isomerase (Probable). Might play a role in the unfolded protein response (Probable). May regulate transport of alpha4-beta2 neuronal acetylcholine receptor (By similarity).|||Secreted under some pathological conditions such as skeletal diseases. http://togogenome.org/gene/10090:Ruvbl1 ^@ http://purl.uniprot.org/uniprot/P60122|||http://purl.uniprot.org/uniprot/Q3U1C2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RuvB family.|||Cytoplasm|||Dynein axonemal particle|||Forms homohexameric rings. Can form a dodecamer with RUVBL2 made of two stacked hexameric rings; however, even though RUVBL1 and RUVBL2 are present in equimolar ratio, the oligomeric status of each hexamer is not known. Oligomerization may regulate binding to nucleic acids and conversely, binding to nucleic acids may affect the dodecameric assembly. Interaction of the complex with DHX34 results in conformational changes of the N-terminus of the RUVBL2 subunits, resulting in loss of nucleotide binding ability and ATP hydrolysis of the complex (By similarity). Interacts with the transcriptional activation domain of MYC. Component of the RNA polymerase II holoenzyme complex. May also act to bridge the LEF1/TCF1-CTNNB1 complex and TBP. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. RUVBL1 interacts with EP400. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Component of the BAF53 complex, at least composed of ACTL6A/BAF53A, RUVBL1/TIP49, SMARCA2/BRM, and TRRAP/PAF400. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Associates with alpha and gamma tubulins, particularly during metaphase and early anaphase. Interacts with NPAT. Component of the chromatin-remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Interacts with IGHMBP2. Interacts with OFD1. Interacts with HINT1. Component of a complex with USP49 and PSMC5. Component of a SWR1-like complex. Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with PIH1D1. Interacts with ITFG1. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation (By similarity). The RUVBL1/RUVBL2 complex interacts with ZNHIT1 (via HIT-type zinc finger), ZNHIT3 (via HIT-type zinc finger), ZNHIT6 (via HIT-type zinc finger) and DDX59/ZNHIT5 (via HIT-type zinc finger) in the presence of ADP (By similarity). Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding (By similarity). Interacts with SMG1 (By similarity).|||Membrane|||Nucleus|||Nucleus matrix|||Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (By similarity). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (By similarity). This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (By similarity). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (By similarity). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (By similarity). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (By similarity). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (By similarity). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (By similarity). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (By similarity). Essential for cell proliferation (By similarity). May be able to bind plasminogen at cell surface and enhance plasminogen activation (By similarity).|||Proposed core component of the chromatin remodeling Ino80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding.|||centrosome|||nucleoplasm http://togogenome.org/gene/10090:Ccdc62 ^@ http://purl.uniprot.org/uniprot/E9PVD1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains 2 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The first one is essential for the association with ESR1 and ESR2 (By similarity).|||Cytoplasm|||Highly expressed in testis, not detected in other tissues (at protein level). Expressed at low levels in the epididymis, lung, spleen, bladder, kidney, liver, muscle.|||Interacts with ESR1 and ESR2 in the presence of estradiol/E2. The interaction with ESR2 recruits CCDC62 to ER target genes, including cyclin-D1/CCND1 AP-1 promoter (By similarity). Interacts with GOPC (PubMed:28339613).|||Nuclear receptor coactivator that can enhance preferentially estrogen receptors ESR1 and ESR2 transactivation. Modulates also progesterone/PGR, glucocorticoid/NR3C1 and androgen/AR receptors transactivation, although at lower level; little effect on vitamin D receptor/VDR (By similarity). Required for normal spermiogenesis (PubMed:28339613). It probably plays a role in acrosome formation (PubMed:28339613).|||Nucleus|||acrosome http://togogenome.org/gene/10090:Lipg ^@ http://purl.uniprot.org/uniprot/C0LQ91|||http://purl.uniprot.org/uniprot/Q3U5K0|||http://purl.uniprot.org/uniprot/Q3U713|||http://purl.uniprot.org/uniprot/Q3U807|||http://purl.uniprot.org/uniprot/Q9WVG5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Exerts both phospholipase and triglyceride lipase activities (By similarity). More active as a phospholipase than a triglyceride lipase (By similarity). Hydrolyzes triglycerides, both with short-chain fatty acyl groups (tributyrin) and long-chain fatty acyl groups (triolein) with similar levels of activity toward both types of substrates (By similarity). Hydrolyzes high density lipoproteins (HDL) more efficiently than other lipoproteins (By similarity).|||Expressed in placenta, lung, liver, testis and spleen.|||Head to tail homodimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Vdac3 ^@ http://purl.uniprot.org/uniprot/Q3TX38|||http://purl.uniprot.org/uniprot/Q5EBQ0|||http://purl.uniprot.org/uniprot/Q60931 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic mitochondrial porin family.|||Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands.|||Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules (By similarity). Involved in male fertility and sperm mitochondrial sheath formation (PubMed:35228556).|||Highest levels of expression detected in testis, less but still abundant expression in heart, kidney, brain, and skeletal muscle.|||Interacts with ARMC12 in a TBC1D21-dependent manner. Interacts with MISFA (PubMed:35228556).|||Male Vdac3-deficient mice are infertile as a result of reduced sperm mobility due to an abnormal mitochondrial sheat in spermatozoa.|||Membrane|||Mitochondrion outer membrane|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Srsf1 ^@ http://purl.uniprot.org/uniprot/Q6PDM2 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Asymmetrically dimethylated at arginines, probably by PRMT1, methylation promotes localization to nuclear speckles.|||Belongs to the splicing factor SR family.|||Consists of two polypeptides of p32 and p33. Identified in the spliceosome C complex. Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF (By similarity). In vitro, self-associates and binds SRSF2, SNRNP70 and U2AF1 but not U2AF2. Binds SREK1/SFRS12. Interacts with SAFB/SAFB1. Interacts with PSIP1/LEDGF. Interacts with RSRC1 (via Arg/Ser-rich domain). Interacts with ZRSR2/U2AF1-RS2. Interacts with CCDC55 (via C-terminus). Interacts with SRPK1 and a sliding docking interaction is essential for its sequential and processive phosphorylation by SRPK1. Interacts with NXF1. Interacts with CCNL1, CCNL2 and CDK11B. Interacts with RRP1B. Interacts (when phosphorylated in its RS domain) with TNPO3; promoting nuclear import. Interacts with ILDR1 (via C-terminus) and ILDR2 (PubMed:28785060).|||Cytoplasm|||Expressed in inner ear.|||May be due to intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus speckle|||Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Phosphorylated by SRPK1 at multiple serines in its RS domain via a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds to a docking groove in the large lobe of the kinase domain of SRPK1 and this induces certain structural changes in SRPK1 and/or RRM 2 domain of SRSF1, allowing RRM 2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM 2, which then docks at the docking groove of SRPK1. This also signals RRM 2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed (By similarity).|||Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing (PubMed:28785060). Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing (By similarity). Specifically regulates alternative splicing of cardiac isoforms of CAMK2D, LDB3/CYPHER and TNNT2/CTNT during heart remodeling at the juvenile to adult transition. The inappropriate accumulation of a neonatal and neuronal isoform of CAMKD2 in the adult heart results in aberrant calcium handling and defective excitation-contraction coupling in cardiomyocytes. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway (PubMed:15652482).|||The RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling (By similarity). http://togogenome.org/gene/10090:Gm20823 ^@ http://purl.uniprot.org/uniprot/Q810R8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Morn4 ^@ http://purl.uniprot.org/uniprot/Q6PGF2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with MYO3A.|||Plays a role in promoting axonal degeneration following neuronal injury by toxic insult or trauma.|||Severed Morn4 null axons show significantly reduced and delayed axonal degeneration following axotomy and protection is evident for at least 72 hrs, whereas wild-type axons degenerate within the first 12 hrs.|||filopodium tip|||stereocilium http://togogenome.org/gene/10090:Naip1 ^@ http://purl.uniprot.org/uniprot/Q9QWK5 ^@ Domain|||Function|||Subunit ^@ Anti-apoptotic protein which acts by inhibiting the activities of CASP3, CASP7 and CASP9. Can inhibit the autocleavage of pro-CASP9 and cleavage of pro-CASP3 by CASP9. Capable of inhibiting CASP9 autoproteolysis at 'Asp-315' and decreasing the rate of auto proteolysis at 'Asp-330'. Acts as a mediator of neuronal survival in pathological conditions. Prevents motor-neuron apoptosis induced by a variety of signals (By similarity).|||Both the BIR and NACHT domains are essential for effective inhibition of pro-CASP9 cleavage. BIR3 domain binds to procaspase-9 and the NACHT domain interacts with the NACHT domain of APAF1 forming a bridge between pro-CASP9 and APAF1 (By similarity).|||Interacts (via NACHT domain) with APAF1 (via CARD and NACHT domains). http://togogenome.org/gene/10090:Mfsd8 ^@ http://purl.uniprot.org/uniprot/Q8BH31 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Endosome membrane|||Lysosome membrane|||Outward-rectifying chloride channel involved in endolysosomal chloride homeostasis, membrane fusion and function. Conducts chloride currents up to hundreds of picoamperes. Regulates lysosomal calcium content by reducing the lysosomal membrane potential, thereby activating TRPML1 channel and further release of lysosomal calcium ions. Regulates the pH in endolysosomal compartments and may contribute to progressive acidification from endosome to lysosome. Permeable to other halides such as iodide and fluoride ions.|||Retinal degeneration associated with blindness. http://togogenome.org/gene/10090:Slc26a1 ^@ http://purl.uniprot.org/uniprot/G5E8U1|||http://purl.uniprot.org/uniprot/P58735|||http://purl.uniprot.org/uniprot/Q3UPH6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Cell membrane|||Expressed in the heart, cecum, calvaria, brain, liver, skeletal muscle and kidney.|||Membrane|||Mice exhibit hyperoxaluria with hyperoxalemia, nephrocalcinosis and calcium oxalate stones in their renal tubules and bladder (PubMed:20160351). They also display hypersulfaturia, hyposulfatemia and enhanced acetaminophen-induced liver toxicity (PubMed:20160351).|||Sodium-independent sulfate anion transporter (PubMed:12590734, PubMed:12217875, PubMed:20160351, PubMed:27210743). Can transport other anions including bicarbonate, thiosulfate and oxalate by mediating sulfate-hydrogencarbonate, sulfate-oxalate and oxalate-hydrogencarbonate anion exchange (PubMed:12590734, PubMed:12217875, PubMed:20160351, PubMed:27210743). Mediates sulfate-thiosulfate anion exchange (By similarity).|||Sodium-independent sulfate anion transporter. Can transport other anions including bicarbonate, thiosulfate and oxalate. http://togogenome.org/gene/10090:Zc3h10 ^@ http://purl.uniprot.org/uniprot/Q8R205 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Specific regulator of miRNA biogenesis. Binds, via the C3H1-type zinc finger domains, to the binding motif 5'-GCAGCGC-3' on microRNA pri-MIR143 and negatively regulates the processing to mature microRNA. http://togogenome.org/gene/10090:Dkk2 ^@ http://purl.uniprot.org/uniprot/Q9QYZ8 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease.|||Belongs to the dickkopf family.|||Expressed in the oral mesenchyme lingual to the developing mandibular tooth buds at 13.5 dpc (PubMed:27713059). Expressed in the developing cochlea at 12.5 and 15.5 dpc (PubMed:27550540). Expressed in the forelimb at 13.5 dpc (PubMed:27550540).|||Interacts with LRP5 and LRP6.|||May be proteolytically processed by a furin-like protease.|||Secreted|||The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6. http://togogenome.org/gene/10090:Pigv ^@ http://purl.uniprot.org/uniprot/Q7TPN3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Alpha-1,6-mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the second mannose to the glycosylphosphatidylinositol during GPI precursor assembly (By similarity).|||Belongs to the PIGV family.|||Endoplasmic reticulum membrane|||Not N-glycosylated. http://togogenome.org/gene/10090:Wnt10b ^@ http://purl.uniprot.org/uniprot/P48614|||http://purl.uniprot.org/uniprot/Q1RME7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Wnt family.|||Expressed in embryos and in the mammary gland of non-pregnant mice.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Specifically activates canonical Wnt/beta-catenin signaling and thus triggers beta-catenin/LEF/TCF-mediated transcriptional programs. Involved in signaling networks controlling stemness, pluripotency and cell fate decisions. Acts in the immune system, mammary gland, adipose tissue, bone and skin.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Or56a5 ^@ http://purl.uniprot.org/uniprot/Q8VGV1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dcc ^@ http://purl.uniprot.org/uniprot/P70211 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. DCC family.|||In the embryo, expressed at high levels in the developing brain and neural tube. In the embryo, expressed in developing neurons of the telencephalic cortical plate and in developing brainstem nuclei (PubMed:28250456). In adult, highly expressed in brain with very low levels found in testis, heart and thymus. Isoform C is expressed only in the embryo.|||Interacts with the cytoplasmic part of UNC5A, UNC5B, UNC5C and probably UNC5D (By similarity). Interacts with MAPK1 (By similarity). Interacts with NTN1 (By similarity). Interacts with DSCAM (PubMed:18585357). Interacts with PTK2/FAK1 (PubMed:15494734). Interacts with MYO10 (PubMed:21321230). Interacts with CBLN4; this interaction can be competed by NTN1 (PubMed:22220752, PubMed:29782851). Interacts with SIAH1 and SIAH2 (By similarity).|||Low levels in early gestation. Highest levels expressed during mid gestation. Levels decrease in late gestation and remain at this level in the adult.|||Membrane|||Produced by alternative initiation at Met-85 of isoform A.|||Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene.|||Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Endod1 ^@ http://purl.uniprot.org/uniprot/Q8C522 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA/RNA non-specific endonuclease family.|||Interacts with RNF26; this interaction is important to modulate innate immune signaling through the cGAS-STING pathway.|||May act as a DNase and a RNase. Plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26.|||Secreted http://togogenome.org/gene/10090:Slc11a2 ^@ http://purl.uniprot.org/uniprot/P49282 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in erythroid precursor cells (at protein level).|||Apical cell membrane|||Belongs to the NRAMP family.|||Cell membrane|||Defects in Slc11a2 are the cause of microcytic anemia (mk). Homozygous mk/mk mice have hypochromic microcytic anemia due to severe defects in intestinal iron absorption and erythroid iron utilization.|||Early endosome membrane|||Expressed in duodenum (at protein level).|||Extracellular vesicle membrane|||Forms a complex with NDFIP1 and NEDD4L, in cortical neurons, in response to iron and cobalt exposure; this interaction leads to SLC11A2 ubiquitination by NEDD4L and proteasome-dependent degradation (By similarity). Interacts with NDFIP1, NDFIP2 and WWP2; this interaction leads to SLC11A2 ubiquitination by WWP2 and subsequent proteasome-dependent degradation (PubMed:18776082). Interacts with COX2 and TOM6 at the outer mitochondrion membrane (By similarity). Interacts with ARRDC1; this interaction regulates the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity). Interacts with ARRDC4; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism (By similarity).|||Late endosome membrane|||Lysosome membrane|||Mice display no apparent anatomical abnormalities. They are however anemic, show progressive postnatal growth retardation, and at birth have elevated liver iron stores compared with wild-type littermates. None survive for more than 7 days. Heterozygotes appear normal, showing no significant hematological abnormalities. However, by 8 weeks, their liver iron content is lower than in wild-type littermates.|||Mitochondrion outer membrane|||N-glycosylated.|||Nifedipine induces duodenal iron accumulation and mobilizes iron from the liver of iron-overloaded mice.|||Proton-coupled metal ion symporter operating with a proton to metal ion stoichiometry of 1:1 (PubMed:16475818). Selectively transports various divalent metal cations, in decreasing affinity: Cd(2+) > Fe(2+) > Co(2+), Mn(2+) >> Zn(2+), Ni(2+), VO(2+) (By similarity) (PubMed:16475818). Essential for maintenance of iron homeostasis by modulating intestinal absorption of dietary Fe(2+) and TF-associated endosomal Fe(2+) transport in erythroid precursors and other cells (PubMed:11739192). Enables Fe(2+) and Mn(2+) ion entry into mitochondria, and is thus expected to promote mitochondrial heme synthesis, iron-sulfur cluster biogenesis and antioxidant defense (By similarity). Can mediate uncoupled fluxes of either protons or metal ions.|||Recycling endosome membrane|||Ubiquitinated by WWP2.|||Up-regulated under iron-depletion conditions in the proximal portion of the duodenum where it is abundantly expressed in the brush border of absorptive epithelial cells (at protein level).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Rph3al ^@ http://purl.uniprot.org/uniprot/Q768S4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in pancreatic islets. High to moderate expression in adrenal gland, pituitary gland and ovary.|||Rab GTPase effector involved in the late steps of regulated exocytosis, both in endocrine and exocrine cells. Regulates the exocytosis of dense-core vesicles in neuroendocrine cells through interaction with RAB27A. Acts as a potential RAB3B effector protein in epithelial cells.|||Recruited to dense-core vesicles through specific interaction with RAB27A in endocrine cells. Interacts with RAB3A, RAB3B, RAB3C and RAB3D. Interacts with ZYX (By similarity).|||The N-terminus of the RabBD domain is necessary and sufficient for interaction with RAB27A.|||secretory vesicle membrane http://togogenome.org/gene/10090:Fkbp1b ^@ http://purl.uniprot.org/uniprot/Q9Z2I2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FKBP-type PPIase family. FKBP1 subfamily.|||Cytoplasm|||Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity).|||Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with RYR2 (By similarity).|||Inhibited by both FK506 and rapamycin.|||Sarcoplasmic reticulum http://togogenome.org/gene/10090:Eif4ebp2 ^@ http://purl.uniprot.org/uniprot/P70445|||http://purl.uniprot.org/uniprot/Q3UFP6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eIF4E-binding protein family.|||Cytoplasm|||Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain. Deamidation promotes interaction with RPTOR, subsequent phosphorylation by mTORC1 and increased translation, leading to impair kinetics of excitatory synaptic transmission. Deamidation takes place during postnatal development, when the PI3K-Akt-mTOR signaling is reduced, suggesting it acts as a compensatory mechanism to promote translation despite attenuated PI3K-Akt-mTOR signaling in neuron development (PubMed:20347422). Deamidation converts Asn residues into a mixture of Asp and isoaspartate; interactions with PCMT1 is required to prevent isoaspartate accumulation and convert isoaspartate to Asp (PubMed:20424163).|||Enriched in brain.|||Hypophosphorylated EIF4EBP2 interacts with EIF4E; phosphorylation of EIF4EBP2 by mTORC1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:20347422, PubMed:23184952). Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp (PubMed:20424163).|||Intrinsically disordered protein that undergoes folding upon phosphorylation. Hypophosphorylated form interacts strongly with EIF4E using (1) the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and (2) the secondary EIF4E binding sites (residues 78-82). Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.|||Mice develop normally and are fertile. They however show defects in synaptic plasticity, impaired spatial learning and memory and conditioned fear-associative memory deficits (PubMed:16237163). Mice show behavior defects and autistic-like phenotype, characterized by social interaction deficits, altered communication and repetitive/stereotyped behaviors: they show an increased ratio of excitatory to inhibitory synaptic inputs possibly due to increased translation of neuroligin family proteins (PubMed:17029989, PubMed:23172145). Mice lacking both Eif4ebp1 and Eif4ebp2 display increased their sensitivity to diet-induced obesity (PubMed:17273556). Mice lacking both Eif4ebp1 and Eif4ebp2 show defects in myelopoiesis: mice display an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements (PubMed:19175792).|||Nucleus|||Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions. First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000. Phosphorylated in response to insulin, EGF and PDGF.|||Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:16237163, PubMed:17029989). Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:17029989, PubMed:20347422, PubMed:23172145). EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (PubMed:20347422, PubMed:24139800, PubMed:23172145). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (PubMed:8939971).|||The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex. http://togogenome.org/gene/10090:Ube2q2 ^@ http://purl.uniprot.org/uniprot/Q8K2Z8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination.|||Auto-ubiquitinated in vitro.|||Belongs to the ubiquitin-conjugating enzyme family.|||Cytoplasm http://togogenome.org/gene/10090:Fpr-rs3 ^@ http://purl.uniprot.org/uniprot/O88537 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed exclusively in vomeronasal neurons (PubMed:19387439, PubMed:19497865). Expressed in 0.8 % of a subset of sensory neurons located in the apical layer of the vomeronasal organ. Localized in sensory somata as well as dendritic cells. Each neuron appears to express only one receptor gene.|||May have an olfactory function associated with the identification of pathogens or of pathogenic states. http://togogenome.org/gene/10090:Cdc14a ^@ http://purl.uniprot.org/uniprot/Q6GQT0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class CDC14 subfamily.|||Composed of two structurally equivalent A and B domains that adopt a dual specificity protein phosphatase (DSP) fold.|||Dual-specificity phosphatase. Required for centrosome separation and productive cytokinesis during cell division. Dephosphorylates SIRT2 around early anaphase. May dephosphorylate the APC subunit FZR1/CDH1, thereby promoting APC-FZR1 dependent degradation of mitotic cyclins and subsequent exit from mitosis (By similarity). Required for normal hearing (PubMed:29293958).|||Expressed in the inner ear.|||Interacts with KIF20A. Interaction is required to localize CDC14 to the midzone of the mitotic spindle (By similarity).|||Nucleus|||centrosome|||kinocilium|||spindle|||spindle pole|||stereocilium http://togogenome.org/gene/10090:Tpm1 ^@ http://purl.uniprot.org/uniprot/A0A2R2Y2P8|||http://purl.uniprot.org/uniprot/B7ZNL3|||http://purl.uniprot.org/uniprot/E9Q448|||http://purl.uniprot.org/uniprot/E9Q450|||http://purl.uniprot.org/uniprot/E9Q452|||http://purl.uniprot.org/uniprot/E9Q453|||http://purl.uniprot.org/uniprot/E9Q454|||http://purl.uniprot.org/uniprot/E9Q455|||http://purl.uniprot.org/uniprot/G5E8R0|||http://purl.uniprot.org/uniprot/G5E8R1|||http://purl.uniprot.org/uniprot/G5E8R2|||http://purl.uniprot.org/uniprot/P58771|||http://purl.uniprot.org/uniprot/Q545Y3|||http://purl.uniprot.org/uniprot/Q564G1|||http://purl.uniprot.org/uniprot/Q8BP43 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tropomyosin family.|||Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.|||Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain. Interacts with HRG (via the HRR domain); the interaction contributes to the antiangiogenic properties of the histidine/proline-rich region (HRR) of HRG. Interacts (via N-terminus) with LMOD2 (via N-terminus) and TMOD1 (via N-terminus).|||Induced in stimulated quiescent cells.|||Phosphorylated at Ser-283 by DAPK1 in response to oxidative stress and this phosphorylation enhances stress fiber formation in endothelial cells.|||The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.|||The sequences of cardiac and skeletal muscles are identical.|||cytoskeleton http://togogenome.org/gene/10090:Smpd3 ^@ http://purl.uniprot.org/uniprot/Q9JJY3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neutral sphingomyelinase family.|||Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization (PubMed:15051724, PubMed:15764706, PubMed:15929065, PubMed:16025116). Binds to anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) that modulate enzymatic activity and subcellular location (PubMed:21550973). May be involved in IL-1-beta-induced JNK activation in hepatocytes (By similarity). May act as a mediator in transcriptional regulation of NOS2/iNOS via the NF-kappa-B activation under inflammatory conditions (By similarity).|||Cell membrane|||Defects in smpd3 are the cause of fragilitas ossium (fro) mutation characterized by severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Mice lacking Smpd2 and Smpd3 are completely devoid of neutral SMase activity but do not developed sphingomyelin storage abnormalities. Mice lacking Smpd3 develop a form of dwarfism and delayed puberty as part of a hypothalamus-induced combined pituitary hormone deficiency (CPHD). Growth retardation is probably due to delayed ossification of long bones.|||Golgi apparatus membrane|||Inhibited by nSMase inhibitor GW4869. Binding of anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) increases enzymatic activity (PubMed:21550973).|||Palmitoylated, palmitoylation-deficient proteins are targeted for lysosomal degradation.|||Predominantly expressed in brain (at protein level). http://togogenome.org/gene/10090:Timm17b ^@ http://purl.uniprot.org/uniprot/Q545H3|||http://purl.uniprot.org/uniprot/Q9Z0V7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tim17/Tim22/Tim23 family.|||Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50.|||Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50. The complex interacts with the TIMM44 component of the PAM complex. The complex also interacts with DNAJC15 (By similarity).|||Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Rnf150 ^@ http://purl.uniprot.org/uniprot/Q5DTZ6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Klk14 ^@ http://purl.uniprot.org/uniprot/Q8CGR5 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Inhibited by SERPINA1, SERPINC1, SERPINE1, SERPINF2, aprotinin, soybean, trypsin inhibitor and leupeptin. Inhibited by serine protease inhibitor SPINK5. Has an autoproteolytic activity which may have a regulatory effect. Activated by citrate and inhibited by zinc and to a lower extent by manganese (By similarity).|||Proteolytic cleavage of the activation peptide produces the active enzyme.|||Serine-type endopeptidase with a dual trypsin-like and chymotrypsin-like substrate specificity. May activate/inactivate the proteinase-activated receptors F2R, F2RL1 and F2RL3 and other kallikreins including KLK1, KLK3, KLK5 and KLK11. May function in seminal clot liquefaction through direct cleavage of the semenogelin SEMG1 and SEMG2 and activation of KLK3. May function through desmoglein DSG1 cleavage in epidermal desquamation a process by which the most superficial corneocytes are shed from the skin surface. May be involved in several aspects of tumor progression including growth, invasion and angiogenesis (By similarity).|||extracellular space http://togogenome.org/gene/10090:Igsf3 ^@ http://purl.uniprot.org/uniprot/Q6ZQA6 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the lacrimal duct and lacrimal gland.|||Expressed in the lacrimal duct at embryonic day (E)19 and in both the lacrimal duct and lacrimal gland at post natal day (P)30.|||Membrane http://togogenome.org/gene/10090:Osr2 ^@ http://purl.uniprot.org/uniprot/Q91ZD1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Odd C2H2-type zinc-finger protein family.|||Decrease in expression of the Wnt signaling genes Dkk2, Sfrp1 and Sfrp2 and an increase in Lef1 and Tcf7 in the mandibular molar tooth mesenchyme at 13.5 dpc.|||First detected at 9.25 dpc, specifically in the mesonephric vesicles. By 10.0 dpc expression is also observed in the rostro-lateral mandibular mesenchyme immediately adjacent to the maxillary processes. In the developing limb buds it is expressed in a unique mesenchymal domain and the onset of the expression follows a distinct dorsal to ventral developmental time sequence beginning in the forelimb and then in the hindlimb. It exhibits a dynamic expression pattern during craniofacial development, in the mandibular and maxillary processes as well as the developing palate. It is also expressed at sites of epithelial-mesenchymal interactions during tooth and kidney development.|||May be involved in the development of the mandibular molar tooth germ at the bud stage.|||Nucleus http://togogenome.org/gene/10090:Bhlha15 ^@ http://purl.uniprot.org/uniprot/Q9QYC3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in pancreatic tissue only in acinar cells. There is a complete absence of expression in intra- or interlobular pancreatic ducts and in all islet cells.|||First observed at 10.5 dpc in the primitive gut and in the developing lung bud. Expression in the gut persists through 16.5 dpc and remains restricted primarily to the epithelial lining of the esophagus, stomach and intestine. Expression in the lung is detected in the bronchial epithelium at 14.5 dpc and at 15.5 dpc. Expressed specifically in acinar cells during pancreatic development. Detected in skeletal muscle tissues beginning at 12.5 dpc, persisting throughout all embryonic stages examined although, in older embryos expression becomes severely reduced.|||Forms homodimers or heterodimers with TCF3 gene products E12 and E47. These dimers bind to the E-box site, however, heterodimer with MYOD1 does not bind target DNA.|||Lacks a classic transcription activation domain and instead possesses an N-terminal region capable of inhibiting heterologous activators.|||Mice display incorrect granule organization in pancreatic acinar cells and other serous exocrine cells such as parotid acini and gastric chief cells. They also display mislocalization of mitochondria and Golgi apparatus and reduced Ca(2+) uptake by mitochondria.|||Nucleus|||Plays a role in controlling the transcriptional activity of MyoD, ensuring that expanding myoblast populations remain undifferentiated (PubMed:17612490). Repression may occur through muscle-specific E-box occupancy by homodimers. May also negatively regulate bHLH-mediated transcription through an N-terminal repressor domain. Serves as a key regulator of acinar cell function, stability, and identity. Also required for normal organelle localization in exocrine cells and for mitochondrial calcium ion transport. May function as a unique regulator of gene expression in several different embryonic and postnatal cell lineages. Binds to the E-box consensus sequence 5'-CANNTG-3'.|||Up-regulated by XBP1. Induced by chemical activators of the unfolded protein response (UPR) such as tunicamycin and thapsigargin, and also by glucose starvation (PubMed:17612490). http://togogenome.org/gene/10090:Mga ^@ http://purl.uniprot.org/uniprot/A2AWL7|||http://purl.uniprot.org/uniprot/E9QLG3|||http://purl.uniprot.org/uniprot/H7BX50 ^@ Caution|||Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with ZMYND11 (By similarity). Interacts with MAX. Requires heterodimerization with MAX for E-box binding.|||Expressed at 9.5 dpc, 10 dpc and 10.5 dpc in the limb buds, branchial arches and the tail region.|||Functions as a dual-specificity transcription factor, regulating the expression of both MAX-network and T-box family target genes. Functions as a repressor or an activator. Binds to 5'-AATTTCACACCTAGGTGTGAAATT-3' core sequence and seems to regulate MYC-MAX target genes. Suppresses transcriptional activation by MYC and inhibits MYC-dependent cell transformation. Function activated by heterodimerization with MAX. This heterodimerization serves the dual function of both generating an E-box-binding heterodimer and simultaneously blocking interaction of a corepressor.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Transcription repression is enhanced or dependent on the presence of the T-box DNA-binding domain. http://togogenome.org/gene/10090:Gm20772 ^@ http://purl.uniprot.org/uniprot/Q3TTD8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Arl5b ^@ http://purl.uniprot.org/uniprot/Q6NXZ5|||http://purl.uniprot.org/uniprot/Q9D4P0 ^@ Function|||Similarity ^@ Belongs to the small GTPase superfamily. Arf family.|||Binds and exchanges GTP and GDP. http://togogenome.org/gene/10090:Wdr4 ^@ http://purl.uniprot.org/uniprot/E9Q156|||http://purl.uniprot.org/uniprot/Q9EP82 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat TRM82 family.|||Chromosome|||Embryonic lethality at E9.5-10.5, possibly caused by DNA damage.|||Non-catalytic component of the METTL1-WDR4 complex, composed of METTL1 and WDR4. Interacts with FEN1; the interaction is direct.|||Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:29983320). In the METTL1-WDR4 methyltransferase complex, WDR4 acts as a scaffold for tRNA-binding (By similarity). Required for the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:29983320). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (By similarity). Also required for the formation of N(7)-methylguanine at internal sites in a subset of mRNAs (By similarity). Also required for methylation of a specific subset of miRNAs, such as let-7 (By similarity). Acts as a regulator of embryonic stem cell self-renewal and differentiation (PubMed:29983320). Independently of METTL1, also plays a role in genome stability: localizes at the DNA replication site and regulates endonucleolytic activities of FEN1 (PubMed:29574139).|||Nucleus|||Required for the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. In the complex, it is required to stabilize and induce conformational changes of the catalytic subunit. http://togogenome.org/gene/10090:Tmc8 ^@ http://purl.uniprot.org/uniprot/B0QZP6|||http://purl.uniprot.org/uniprot/B0QZP7|||http://purl.uniprot.org/uniprot/B1ATC0|||http://purl.uniprot.org/uniprot/Q7TN58 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMC family.|||Endoplasmic reticulum membrane|||Expressed in thymus, lung, prostate, placenta, testis and spleen.|||Interacts with CIB1.|||Membrane|||Probable ion channel. http://togogenome.org/gene/10090:Atp1b2 ^@ http://purl.uniprot.org/uniprot/P14231|||http://purl.uniprot.org/uniprot/Q3UR55 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the X(+)/potassium ATPases subunit beta family.|||Cell membrane|||Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.|||Membrane|||The C-terminal lobe folds into an immunoglobulin-like domain and mediates cell adhesion properties.|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with isoform 2 of BSG (PubMed:12558975).|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane.|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known. http://togogenome.org/gene/10090:Serpina6 ^@ http://purl.uniprot.org/uniprot/Q06770|||http://purl.uniprot.org/uniprot/Q3UKW1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Expressed by the liver; secreted in plasma.|||Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.|||Proteolytic cleavage leads to an important conformation change. This reduces the affinity for steroids (By similarity).|||Secreted http://togogenome.org/gene/10090:Msrb2 ^@ http://purl.uniprot.org/uniprot/Q78J03 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MsrB Met sulfoxide reductase family.|||Binds 1 zinc ion per subunit.|||Inhibited by high concentrations of substrate.|||Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine. While in many cases, methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residue. Upon oxidative stress, may play a role in the preservation of mitochondrial integrity by decreasing the intracellular reactive oxygen species build-up through its scavenging role, hence contributing to cell survival and protein maintenance.|||Mitochondrion http://togogenome.org/gene/10090:Krt71 ^@ http://purl.uniprot.org/uniprot/Q9R0H5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed exclusively in the inner root sheath (IRS) of anagen hair follicles, where expression is predominantly in the hair cone during anagen III and in the Huxley and Henle layers of the inner root sheath during anagen VI.|||Heterodimer of a type I and a type II keratin. Associates with KRT16 and/or KRT17.|||Mice exhibit defects in hair structure and progressive alopecia. Missense mutations cause milder phenotypes such as caracul, characterized by rough and greasy fur, and wavy hair that is pointed in different directions.|||Plays a central role in hair formation. Essential component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle.|||Specifically expressed in the inner root sheath (IRS) of the hair follicle. Present in Henle and the Huxley layers of the IRS, while expression in the cuticle is unsure (at protein level).|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).|||cytoskeleton http://togogenome.org/gene/10090:Mcpt9 ^@ http://purl.uniprot.org/uniprot/O35164 ^@ Similarity|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Selectively expressed in uterine mast cells. http://togogenome.org/gene/10090:Klf4 ^@ http://purl.uniprot.org/uniprot/Q60793 ^@ Biotechnology|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||By interferon-gamma in Stat1-dependent manner.|||Cytoplasm|||Death shortly after birth due to loss of epidermal barrier function resulting from perturbation of late-stage epidermal differentiation structures including the cornified envelope. When selectively deleted in the surface ectoderm-derived structures of the eye, embryos develop normally and adults are viable and fertile but mutants display down-regulation of Krt12 and Aqp5 and multiple ocular defects including corneal epithelial fragility, stromal edema, defective lens and loss of conjunctival goblet cells.|||Highest expression in the colon. Lower levels in testis, lung and small intestine.|||Interacts with MUC1 (via the C-terminal domain) (By similarity). Interacts with POU5F1/OCT4 and SOX2 (PubMed:19816951). Interacts with MEIS2 isoform MeisD and PBX1 isoform PBX1a (By similarity). Interacts with ZNF296 (PubMed:24161396). Interacts with GLIS1 (By similarity). Interacts with BTRC; this interaction leads to KLF4 ubiquitination and subsequent degradation (PubMed:29593216). Interacts with IPO7; the interaction facilitates nuclear translocation of KLF4 in dental papilla cells (PubMed:35922041).|||Nucleus|||POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.|||Polyglutamylated by TTLL1 and TTLL4 at Glu-381, which inhibits KLF4 binding with E3 ligase component BTRC, thereby impeding ubiquitination (PubMed:29593216). Deglutamylated by CCP1 and CCP6; deglutamylation promotes KLF4 ubiquitination (PubMed:29593216). KLF4 glutamylation state plays a critical role in the regulation of its function in cell reprogramming, pluripotency maintenance and embryogenesis (PubMed:29593216).|||Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216). Binds to the promoter region of its own gene and can activate its own transcription (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216). Regulates the expression of key transcription factors during embryonic development (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216). Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216). Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription (By similarity).|||Ubiquitinated. 'Lys-48'-linked ubiquitinated and targeted for proteasomal degradation by the SCF(BTRC) E3 ubiquitin-protein ligase complex, thereby negatively regulating cell pluripotency maintenance and embryogenesis.|||the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Csmd2 ^@ http://purl.uniprot.org/uniprot/V9GX34 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Gm5891 ^@ http://purl.uniprot.org/uniprot/Q3UT86 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:St3gal4 ^@ http://purl.uniprot.org/uniprot/Q91Y74 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A beta-galactoside alpha2-3 sialyltransferase involved in terminal sialylation of glycoproteins and glycolipids (PubMed:12097641) (By similarity). Catalyzes the transfer of sialic acid (N-acetyl-neuraminic acid; Neu5Ac) from the nucleotide sugar donor CMP-Neu5Ac onto acceptor Galbeta-(1->3)-GalNAc- and Galbeta-(1->4)-GlcNAc-terminated glycoconjugates through an alpha2-3 linkage (PubMed:9184827) (By similarity). Plays a major role in hemostasis. Responsible for sialylation of plasma VWF/von Willebrand factor, preventing its recognition by asialoglycoprotein receptors (ASGPR) and subsequent clearance. Regulates ASGPR-mediated clearance of platelets (PubMed:12097641). Participates in the biosynthesis of the sialyl Lewis X epitopes, both on O- and N-glycans, which are recognized by SELE/E-selectin, SELP/P-selectin and SELL/L-selectin. Essential for selectin-mediated rolling and adhesion of leukocytes during extravasation (PubMed:25498912). Contributes to adhesion and transendothelial migration of neutrophils likely through terminal sialylation of CXCR2 (PubMed:18519646). In glycosphingolipid biosynthesis, sialylates GM1 and GA1 gangliosides to form GD1a and GM1b, respectively (By similarity). Metabolizes brain c-series ganglioside GT1c forming GQ1c (By similarity). Synthesizes ganglioside LM1 (IV3Neu5Ac-nLc4Cer), a major structural component of peripheral nerve myelin (By similarity).|||Belongs to the glycosyltransferase 29 family.|||Broadly expressed among tissues with highest levels in the small intestine and colon.|||Golgi stack membrane|||Knockout mice suffer from bleeding disorders and thrombocytopenia due to deficient ASGPR-mediated clearance of plasma VWF/von Willebrand factor. http://togogenome.org/gene/10090:Zfp932 ^@ http://purl.uniprot.org/uniprot/E9QAG8 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain, heart, lung, thymus, spleen, lymph node, liver, kidney, muscle, testis, ovary, skin and uterus.|||Expressed in limb mesenchyme at 10.5 dpc. Expressed in tooth, submandibular glands, thymus, thyroid, vibrissa follicles at 14.5 dpc.|||Interacts (via KRAB domain) with HDAC2; the interaction is direct. Interacts (via KRAB domain) with HDAC1.|||Nucleus|||Sequence-specific DNA binding transcriptional repressor. Represses target gene transcription by recruiting HDAC1 and HDAC2 histone deacetylases. Acts as a specific transcriptional repressor for PTCH1 during embryonic development. Required for osteoblast differentiation and sonic hedgehog/SHH signaling response. Binds to the consensus site 5'-GCGCCC-3' in the promoter of PTCH1.|||The KRAB domain is necessary for its repressive activity. http://togogenome.org/gene/10090:Pmf1 ^@ http://purl.uniprot.org/uniprot/Q9CPV5 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By polyamine analogs in M1 myeloid leukemia cells.|||Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Interacts with COPS7A (By similarity). Interacts via its coiled-coil domain with the leucine-zipper domain of NFE2L2. The interaction with NFE2L2 is required for the transcriptional regulation of SSAT.|||Nucleus|||Part of the MIS12 complex which is required for normal chromosome alignment and segregation and for kinetochore formation during mitosis (By similarity). May act as a cotranscription partner of NFE2L2 involved in regulation of polyamine-induced transcription of SSAT.|||kinetochore http://togogenome.org/gene/10090:Mcu ^@ http://purl.uniprot.org/uniprot/Q3UMR5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MCU (TC 1.A.77) family.|||Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (By similarity). Heterooligomer with CCDC109B/MCUB; this inhibits channel activity (PubMed:23900286). Homooligomer. Homotetramer (PubMed:23900286). Interacts with MICU1; MICU1 acts as an essential regulator for MCU. Interacts with MCUR1. Interactions with MICU1 and MCUR1 are mutually exclusive. Interacts with MICU2 (By similarity). Interacts with SLC25A23 (By similarity).|||Detected in heart muscle (at protein level) (PubMed:26057074). Expressed in skeletal muscle, heart, kidney, liver, brain, lung, white fat and spleen.|||Forms a well-packed pentamer with an overall cylindrical shape. The inner core of the pentamer is formed with the second transmembrane region and the second coiled-coil region: while the transmembrane regions pack into a five-helix bundle having a largely polar pore across the membrane, the coiled-coil outside the membrane forms a pentamer with a hydrophobic core. The inner core is wrapped by the first transmembrane region through contacts between the first and the second transmembrane regions. The second transmembrane is followed by the inner juxtamembrane region (IJMH) that orients at a wide angle relative to the second transmembrane. The two core domains are held together on the periphery by the outer juxtamembrane helix (OJMH).|||Inhibited by ruthenium red or its derivative Ru360.|||Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria (PubMed:21685886, PubMed:23900286, PubMed:24212091). Constitutes the pore-forming and calcium-conducting subunit of the uniporter complex (uniplex) (By similarity). Activity is regulated by MICU1 and MICU2 (By similarity). At low Ca(2+) levels MCU activity is down-regulated by MICU1 and MICU2; at higher Ca(2+) levels MICU1 increases MCU activity (By similarity). Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways (By similarity). Involved in buffering the amplitude of systolic calcium rises in cardiomyocytes (By similarity). While dispensable for baseline homeostatic cardiac function, acts as a key regulator of short-term mitochondrial calcium loading underlying a 'fight-or-flight' response during acute stress: acts by mediating a rapid increase of mitochondrial calcium in pacemaker cells (PubMed:26119742, PubMed:26119731, PubMed:25603276). Participates in mitochondrial permeability transition during ischemia-reperfusion injury (PubMed:26119731). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (By similarity). Mitochondrial calcium uptake in skeletal muscle cells is involved in muscle size in adults (PubMed:25732818). Regulates synaptic vesicle endocytosis kinetics in central nerve terminal (PubMed:26644474). Involved in antigen processing and presentation (PubMed:25251370).|||Mitochondrion inner membrane|||No visible phenotype (PubMed:24212091, PubMed:26057074). Although slightly smaller, mice are grossly normal. Only minor alterations in basal energetics are observed. Cells show a strong reduction, but not a complete absence, of mitochondrial matrix calcium. The skeletal muscles exhibit alterations in the phosphorylation and activity of pyruvate dehydrogenase and mice show defects in ability to perform strenuous work. Mitochondria lack evidence for calcium-induced permeability transition pore (PTP) opening (PubMed:24212091). Mitochondria from mutant mouse heart muscle have impaired Ca(2+) uptake and reduced Ca(2+) levels in the mitochondrial matrix; still, mutant mice have apparently normal heart function and display no cardiac defects (PubMed:26057074). Conditional mutant mice with cardiomyocyte-specific deletion of Mcu in adults display no overt baseline phenotype and are protected against mitochondrial calcium overload by preventing the activation of the mitochondrial permeability transition pore (PubMed:26119742, PubMed:26119731). Mice however lack contractile responsiveness to acute stress and 'fight-or-flight' response: they produce mitochondria refractory to acute calcium uptake, with impaired ATP production and inhibited mitochondrial permeability transition pore opening upon acute calcium challenge (PubMed:26119742, PubMed:26119731).|||Phosphorylation by CaMK2 in heart leads to increased MCU current. The regulation of MCU by CaMK2 is however subject to discussion: another group was unable to reproduce these results. Phosphorylated on tyrosines by PTK2B/PYK2, promoting oligomerization.|||The N-terminal domain is required for efficient Ca(2+) uptake and for interaction with MCUR1. It is not required for targeting to the mitochondria, oligomerization, interaction with MICU1 and MICU2, or assembly of the uniplex complex.|||The critical DXXE motif connecting the transmembrane regions forms a pentameric barrel that constitutes the mouth of the pore. Inside the barrel, two acidic residues are in position to form two carboxylate rings. In absence of SMDT1/EMRE regulator, the calcium ions cannot exit the channel, suggesting that SMDT1/EMRE-binding induces conformational rearrangements to allow calcium to exit. http://togogenome.org/gene/10090:Syt13 ^@ http://purl.uniprot.org/uniprot/Q9EQT6 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Cytoplasmic vesicle membrane|||Expressed in brain, heart, spleen, lung and testis.|||Expressed in embryo at 7 dpc onwards.|||Interacts with NRXN1.|||May be involved in transport vesicle docking to the plasma membrane.|||The first C2 domain/C2A does not mediate Ca(2+)-dependent phospholipid binding.|||The second C2 domain/C2B domain binds phospholipids regardless of whether calcium is present. http://togogenome.org/gene/10090:Btg4 ^@ http://purl.uniprot.org/uniprot/O70552 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Adapter protein that bridges CNOT7, a catalytic subunit of the CCR4-NOT complex, to EIF4E, and facilitates maternal mRNAs decay during the maturation of oocytes and in the fertilized egg (PubMed:27065194). It is therefore required for the maternal-zygotic transition (MZT), zygotic cleavage and initiation of embryonic development (PubMed:27065194).|||BTG4-null mice are viable, have body sizes similar to those of their wild type littermates, are healthy up to 1 year of age, and do not spontaneously develop tumors. Females are sterile and their embryos are arrested at the one- or two-cells stage.|||Belongs to the BTG family.|||Expressed in oocytes (PubMed:27065194). Expressed in testis and in olfactory epithelium.|||Interacts with CNOT7 and EIF4E (PubMed:27065194). Interacts with CNOT8 (PubMed:27065194). http://togogenome.org/gene/10090:Thg1l ^@ http://purl.uniprot.org/uniprot/Q9CQT0|||http://purl.uniprot.org/uniprot/Q9CY52 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage.|||Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage. This step is essential for proper recognition of the tRNA and for the fidelity of protein synthesis. Also functions as a guanyl-nucleotide exchange factor/GEF for the MFN1 and MFN2 mitofusins thereby regulating mitochondrial fusion. By regulating both mitochondrial dynamics and bioenergetic function, it contributes to cell survival following oxidative stress.|||Belongs to the tRNA(His) guanylyltransferase family.|||Binds 2 magnesium ions per subunit.|||Cytoplasm|||Homotetramer. Interacts with MFN1 and MFN2; functions as a guanyl-nucleotide exchange factor/GEF for MFN2 and also probably MFN1.|||Mitochondrion http://togogenome.org/gene/10090:Minpp1 ^@ http://purl.uniprot.org/uniprot/Q9Z2L6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to produce phospho-D-glycerate without formation of 3-phosphoglycerate (By similarity). Acts as a phosphoinositide 5- and phosphoinositide 6-phosphatase and regulates cellular levels of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). May play a role in bone development (endochondral ossification). May play a role in the transition of chondrocytes from proliferation to hypertrophy (By similarity). Through the regulation of intracellular inositol polyphosphates, may control intracellular cation homeostasis, including that of calcium and iron, hence affecting free cation availability required for neural cell signaling (PubMed:33257696).|||Belongs to the histidine acid phosphatase family. MINPP1 subfamily.|||Cell membrane|||Endoplasmic reticulum lumen|||Expressed in different stages of embryogenesis, from 7.5 dpc through 14.5 dpc. The highest levels of expression is found in the visceral endoderm at 7.5 dpc and 8.5 dpc and in the fetal liver at 12.5 dpc and 14.5 dpc.|||Knockout mice are born at Mendelian ratio and are fertile. Although brain histology does not identify major differences in cerebellar or cerebral cortex architecture, a mild, but significant 10% decrease in the brain weight was identified associated with a reduced cortical thickness in homozygous mutant mice at postnatal day 21 (PubMed:33257696). At 14.5 dpc, neural progenitors show a decrease of about one third in intracellular free Ca(2+) levels compared to wild-type progenitors (PubMed:33257696).|||Widely expressed with highest levels in kidney, intestine, thymus and liver. http://togogenome.org/gene/10090:Tcf4 ^@ http://purl.uniprot.org/uniprot/Q60722 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Isoform 2 seems to form inactive heterodimers with MYOD1. Interacts with HIVEP2. Interacts with NEUROD2. Interacts with AGBL1 (By similarity). Interacts with BHLHA9.|||Expressed in proliferative zones during development and in the adult in areas of neuronal plasticity. At 12 dpc, expression is localized in the cortex, cerebellum, pons, medulla and spinal cord. From 18 dpc to adulthood, high levels of expression are found in the pyramidal cells of hippocampal layers CA1-CA4, and in the granular cells of the dentate gyrus. At postnatal day 7, expression is high in the visual cortex and in the subependymal region extending from the anterior lateral ventricle into the olfactory bulb.|||Expressed in the cerebral cortex, Purkinje and granule cell layers of the cerebellum, olfactory neuroepithelium, pyramidal cells of hippocampal layers CA1-CA4, and in the granular cells of the dentate gyrus.|||Nucleus|||Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Isoform 2 inhibits MYOD1 activation of the cardiac alpha-actin promoter. Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription. May have a regulatory function in developmental processes as well as during neuronal plasticity. http://togogenome.org/gene/10090:Taar5 ^@ http://purl.uniprot.org/uniprot/B2RTA0|||http://purl.uniprot.org/uniprot/Q5QD14 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Olfactory receptor specific for trimethylamine, a trace amine enriched in the urine of male mice, playing a role in social behavior. Trimethylamine is present at high concentration in the urine of male mice after puberty and acts as an attractant. This receptor is probably mediated by the G(s)-class of G-proteins which activate adenylate cyclase.|||Specifically expressed in neurons of the olfactory epithelium, to discrete glomeruli predominantly localized to a confined bulb region. Present in the dorsal area of the main olfactory epithelium.|||Trimethylamine is a bacterial metabolite found in some animal odors, and is a repulsive odor associated with bad breath and spoiled food for most organisms, except for M.musculus, where it acts as an attractant (PubMed:16878137, PubMed:23177478). http://togogenome.org/gene/10090:Cd55 ^@ http://purl.uniprot.org/uniprot/Q61475 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the receptors of complement activation (RCA) family.|||Brain, secretory epithelia, skeletal muscle, liver, testes, thymus, spleen and lymph node.|||Cell membrane|||The first Sushi domain (SCR1) is not necessary for function. SCR2 and SCR4 provide the proper conformation for the active site on SCR3 (By similarity).|||This protein recognizes C4b and C3b fragments that condense with cell-surface hydroxyl or amino groups when nascent C4b and C3b are locally generated during C4 and c3 activation. Interaction of daf with cell-associated C4b and C3b polypeptides interferes with their ability to catalyze the conversion of C2 and factor B to enzymatically active C2a and Bb and thereby prevents the formation of C4b2a and C3bBb, the amplification convertases of the complement cascade. Inhibits complement activation by destabilizing and preventing the formation of C3 and C5 convertases, which prevents complement damage. http://togogenome.org/gene/10090:Zfp280d ^@ http://purl.uniprot.org/uniprot/Q68FE8|||http://purl.uniprot.org/uniprot/V9GWW1|||http://purl.uniprot.org/uniprot/V9GXP2 ^@ Function|||Subcellular Location Annotation ^@ May function as a transcription factor.|||Nucleus http://togogenome.org/gene/10090:Cop1 ^@ http://purl.uniprot.org/uniprot/Q9R1A8 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COP1 family.|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in JUN ubiquitination and degradation. Directly involved in p53 (TP53) ubiquitination and degradation, thereby abolishing p53-dependent transcription and apoptosis. Ubiquitinates p53 independently of MDM2 or RCHY1. Probably mediates E3 ubiquitin ligase activity by functioning as the essential RING domain subunit of larger E3 complexes. In contrast, it does not constitute the catalytic RING subunit in the DCX DET1-COP1 complex that negatively regulates JUN, the ubiquitin ligase activity being mediated by RBX1. Involved in 14-3-3 protein sigma/SFN ubiquitination and proteasomal degradation, leading to AKT activation and promotion of cell survival. Ubiquitinates MTA1 leading to its proteasomal degradation. Upon binding to TRIB1, ubiquitinates CEBPA, which lacks a canonical COP1-binding motif.|||Homodimer. Homodimerization is mediated by the coiled coil domain. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Isoform 2 does not interact with CUL4A but still binds to RBX1, suggesting that the interaction may be mediated by another cullin protein. Isoform 1 and isoform 2 interact with CUL5 but not with CUL1, CUL2 not CUL3. Interacts with bZIP transcription factors JUN, JUNB and JUND but not with FOS, ATF2 nor XBP1. Interacts with p53 (TP53). Interacts with COPS6; this interaction stabilizes RFWD2 through reducing its auto-ubiquitination and decelerating its turnover rate. Interacts with SFN; this interaction leads to SFN degradation. Interacts with p53/TP53 and MTA1. Interacts with TRIB1 (via C-terminus) and TRIB2.|||Nucleus speckle|||TRIB1 competes with substrates for RFWD2 binding.|||The RING finger domain, in addition to its role in ubiquitination, functions as a structural scaffold to bring two clusters of positive-charged residues within spatial proximity to mimic a bipartite nuclear localization signal (NLS).|||The WD40 domain (386-731) is necessary and sufficient for TRIB1 binding. http://togogenome.org/gene/10090:Cstf3 ^@ http://purl.uniprot.org/uniprot/Q99LI7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. The CSTF complex is composed of CSTF1 (50 kDa subunit), CSTF2 (64 kDa subunit) and CSTF3 (77 kDa subunit). CSTF3 directly interacts with CSTF1 and CSTF2. Interacts with FIP1L1 (By similarity).|||Nucleus|||One of the multiple factors required for polyadenylation and 3'-end cleavage of mammalian pre-mRNAs. http://togogenome.org/gene/10090:Or4c116 ^@ http://purl.uniprot.org/uniprot/L7MU53 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krt6b ^@ http://purl.uniprot.org/uniprot/Q3UV11 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Shf ^@ http://purl.uniprot.org/uniprot/Q8CG80 ^@ Function|||PTM|||Subunit ^@ Adapter protein which may play a role in the regulation of apoptosis in response to PDGF.|||Interacts with phosphorylated 'Tyr-720' of PDGFRA via its SH2 domain.|||May become phosphorylated upon binding to PDGFRA. http://togogenome.org/gene/10090:Or51q1c ^@ http://purl.uniprot.org/uniprot/Q8VH20 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnni3k ^@ http://purl.uniprot.org/uniprot/Q5GIG6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cytoplasm|||Interacts with TNNI3, ACTC, ACTA1, MYBPC3, AIP, FABP3 and HADHB.|||May play a role in cardiac physiology.|||Nucleus http://togogenome.org/gene/10090:Gpr157 ^@ http://purl.uniprot.org/uniprot/Q148S2|||http://purl.uniprot.org/uniprot/Q8C206 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Expressed in the primary cilia of radial glial progenitors (RGPs) in the developing neocortex (PubMed:27142930).|||Membrane|||Orphan receptor that promotes neuronal differentiation of radial glial progenitors (RGPs) (PubMed:27142930). The activity of this receptor is mediated by a G(q)-protein that activates a phosphatidylinositol-calcium second messenger (PubMed:27142930).|||Preferential expression during the early to mid stages of corticogenesis. High levels in the early radial glial progenitors from 10 to 17 dpc and gradually decrease thereafter (at protein level) (PubMed:27142930).|||cilium membrane http://togogenome.org/gene/10090:Fam13a ^@ http://purl.uniprot.org/uniprot/Q8BGI4 ^@ Similarity|||Tissue Specificity ^@ Belongs to the FAM13 family.|||Expressed in the mammary gland, with similar levels at all stages of development, including pregnancy, lactation and involution. http://togogenome.org/gene/10090:Tasor2 ^@ http://purl.uniprot.org/uniprot/Q5DTT3 ^@ Sequence Caution|||Similarity ^@ Belongs to the TASOR family.|||Contaminating sequence. Potential poly-A sequence. http://togogenome.org/gene/10090:Tmem233 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQE1|||http://purl.uniprot.org/uniprot/D3Z1U7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CD225/Dispanin family.|||Membrane http://togogenome.org/gene/10090:Tacstd2 ^@ http://purl.uniprot.org/uniprot/Q8BGV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the EPCAM family.|||Expressed in kidney, lung, ovary and testis. High levels of expression in immortalized keratinocytes.|||May function as a growth factor receptor.|||Membrane http://togogenome.org/gene/10090:Dis3l ^@ http://purl.uniprot.org/uniprot/Q8C0S1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNR ribonuclease family.|||Component of the RNA exosome complex. The catalytically inactive RNA exosome core (Exo-9) complex is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms (By similarity).|||Cytoplasm|||Putative cytoplasm-specific catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. http://togogenome.org/gene/10090:Ficd ^@ http://purl.uniprot.org/uniprot/Q8BIX9 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-AMPylated in vitro.|||Belongs to the fic family.|||Divalent metal cation. Prefers Mn(2+) over Mg(2+).|||Endoplasmic reticulum membrane|||Homodimer. Interacts with HD.|||Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (By similarity). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates (By similarity).|||The fido domain mediates the adenylyltransferase activity.|||The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity). http://togogenome.org/gene/10090:Art2b ^@ http://purl.uniprot.org/uniprot/O35975 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Arg-specific ADP-ribosyltransferase family.|||Cell membrane|||Expressed in spleen, intestine and thymus.|||Has both NAD(+) glycohydrolase and ADP-ribosyltransferase activity. http://togogenome.org/gene/10090:Or2h1b ^@ http://purl.uniprot.org/uniprot/Q6UAH1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Usp2 ^@ http://purl.uniprot.org/uniprot/O88623 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family. USP2 subfamily.|||Circadian clock output effector that regulates Ca(2+) absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine.|||Cleavage is inhibited by ubiquitin in a dosage-dependent manner. Cleavage is blocked by ubiquitin aldehyde.|||Cytoplasm|||Expressed in a circadian manner in the intestine.|||Found in trimeric complex with MDM2 and MDM4 and USP2. Interacts with CCND1; the interaction is direct and promotes its stabilization by antagonizing ubiquitin-dependent degradation. Interacts (via N-terminus and C-terminus) with MDM2. Interacts with MDM4 and PER1 (By similarity). Homooligomer. Interacts with KCNQ1; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores plasma membrane localization of KCNQ1 (By similarity). Isoform 2: Interacts with NHERF4 and CLTC (PubMed:26756164).|||Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (By similarity). Isoform 1 and isoform 2 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (By similarity). Has no deubiquitinase activity against p53/TP53 (By similarity). Prevents MDM2-mediated degradation of MDM4 (By similarity). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (PubMed:23213472, PubMed:25238854, PubMed:26756164). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (PubMed:23213472). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and BMAL1 (PubMed:25238854).|||Isoform 1: Expressed in heart, liver, kidney, pancreas and to a lower extent in skeletal muscle, brain and testis (at protein level) (PubMed:14686789). Expressed in testis, brain, heart and skeletal muscle (PubMed:14686789, PubMed:26756164). Not detected in the small intestine (PubMed:26756164). Isoform 2: Expressed in the small intestine (PubMed:26756164).|||Membrane|||No stage-dependent developmental pattern of expression is detected. First detected throughout 7.5 dpc embryos.|||Nucleus|||The different N-terminus extensions of isoform 1 and isoform 2 determine their respective subcellular localization and differentiel effect on myoblast fusion and accumulation of muscle-specific proteins. The different N-terminus extensions of isoform 1 and isoform 4 are not essential for their catalytic activity.|||perinuclear region http://togogenome.org/gene/10090:Defb42 ^@ http://purl.uniprot.org/uniprot/Q8BVB5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||By androgens.|||Epididymis-specific, with highest levels in the initial segment and distal caput.|||Has bactericidal activity (By similarity). May play a role in the antimicrobial protection of sperm and urogenital tract epithelia (PubMed:16023745).|||Secreted http://togogenome.org/gene/10090:Rpe65 ^@ http://purl.uniprot.org/uniprot/Q91ZQ5 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the carotenoid oxygenase family.|||Binds 1 Fe(2+) ion per subunit.|||Cell membrane|||Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore (PubMed:15765048, PubMed:9843205, PubMed:23407971, PubMed:28500718). Essential for the production of 11-cis retinal for both rod and cone photoreceptors (PubMed:17251447). Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid. The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT (By similarity).|||Cytoplasm|||Defects in Rpe65 are the cause of light damage susceptibility (LDS) of the retina.|||Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.|||Mice exhibit changes in retinal physiology and biochemistry. Outer segment disks of rod photoreceptors are disorganized, rod function is abolished although cone function remains. Mice lack rhodopsin, but not opsin apoprotein. Furthermore, all-trans-retinyl esters over-accumulate in the retinal pigment epithelium, whereas 11-cis-retinyl esters are absent.|||Microsome membrane|||Palmitoylation by LRAT regulates ligand binding specificity; the palmitoylated form (membrane form) specifically binds all-trans-retinyl-palmitate, while the soluble unpalmitoylated form binds all-trans-retinol (vitamin A).|||Retinal pigment epithelium specific. http://togogenome.org/gene/10090:Gal3st2b ^@ http://purl.uniprot.org/uniprot/J3QMJ1|||http://purl.uniprot.org/uniprot/Q6XQH0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the galactose-3-O-sulfotransferase family.|||Golgi stack membrane|||Strongly inhibited by Cu(2+) and Zn(2+).|||Transfers a sulfate group to the hydroxyl group at C3 of non-reducing beta-galactosyl residues. Acts both on type 1 (Gal-beta-1,3-GlcNAc) and type 2 (Gal-beta-1,4-GlcNAc) chains with similar efficiency (By similarity). http://togogenome.org/gene/10090:Elp1 ^@ http://purl.uniprot.org/uniprot/Q7TT37 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELP1/IKA1 family.|||Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (By similarity). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:23717213). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (PubMed:22854966). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (By similarity).|||Conditional knockout in male germ cells results in defects in wobble uridine tRNA modification and defects in synapsis and meiotic recombination which result in increased apoptosis and complete arrest of gametogenesis, leading to male infertility (PubMed:23717213). Conditional knockout in female germ cells results in female subfertility with reduced litter size although ovaries are morphologically and histologically indistinguishable from those of controls (PubMed:31827135). Oocytes show aneuploidy, reduced alpha-tubulin acetylation and are unable to complete meiosis with defects in meiotic spindle organization, chromosome alignment and kinetochore function (PubMed:31827135). Embryos derived from Elp1-deficient oocytes exhibit digyny, progressive delays in preimplantation development and severe degeneration before reaching the blastocyst stage (PubMed:31827135).|||Cytoplasm|||During spermatogenesis, expressed in the testis in all male germ cell stages except elongated spermatids (at protein level) (PubMed:23717213). Highly expressed in fully-grown germinal vesicle oocytes and modest expression throughout the preimplantation stage with a slight down-regulation at the 2-cell stage (PubMed:31827135). In the embryo, expressed at embryonic days 7, 11, 15 and 17 with the highest expression at embryonic day 11 (PubMed:11747609).|||Homodimer; dimerization promotes ELP1 stability and elongator complex formation. Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6. Interacts preferentially with MAP3K14/NIK followed by IKK-alpha and IKK-beta.|||In the testis, expression is restricted to germ cells during spermatogenesis with no expression detected in somatic cells such as Sertoli cells or Leydig cells (at protein level) (PubMed:23717213). In the ovary, expressed in oocytes of primary, secondary and antral follicles (at protein level) (PubMed:31827135). Widely expressed in adult tissues with highest levels in brain and also expressed at all embryonic stages (PubMed:11747609).|||Nucleus|||Phosphorylated.|||The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification. http://togogenome.org/gene/10090:Casc3 ^@ http://purl.uniprot.org/uniprot/Q8K3W3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination (By similarity).|||Belongs to the CASC3 family.|||Cytoplasm|||Cytoplasmic ribonucleoprotein granule|||High levels in heart, brain, including hippocampus and cerebellum, liver, kidney and testis; lower levels in muscle, lung and spleen.|||Identified in the spliceosome C complex. Component of the mRNA splicing-dependent exon junction complex (EJC), which contains at least CASC3, EIF4A3, MAGOH, NXF1 and RBM8A/Y14. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro) (By similarity). Forms homooligomers (By similarity). Interacts with STAU in an RNA-dependent manner (PubMed:12843282). Interacts with DHX34; the interaction is RNA-independent (By similarity).|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homomer.|||Stress granule|||The coiled coil domain may be involved in oligomerization.|||Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation.|||dendrite|||perinuclear region http://togogenome.org/gene/10090:Rnf40 ^@ http://purl.uniprot.org/uniprot/Q3U319 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BRE1 family.|||Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively). It thereby plays a central role in histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes.|||Component of the RNF20/40 complex (also known as BRE1 complex) probably composed of 2 copies of RNF20/BRE1A and 2 copies of RNF40/BRE1B. Interacts with UBE2E1/UBCH6. Interacts with RB1 and WAC.|||Nucleus http://togogenome.org/gene/10090:Nipa2 ^@ http://purl.uniprot.org/uniprot/Q9JJC8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a selective Mg(2+) transporter.|||Belongs to the NIPA family.|||Cell membrane|||Early endosome|||Up-regulated by low magnesium ion levels.|||Widely expressed. Expressed at high levels in the kidney. http://togogenome.org/gene/10090:Plbd1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B2|||http://purl.uniprot.org/uniprot/Q8VCI0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phospholipase B-like family.|||Exhibits weak phospholipase activity, acting on various phospholipids, including phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and lysophospholipids. However, in view of the small size of the putative binding pocket, it has been proposed that it may act rather as an amidase or a peptidase (By similarity).|||Lysosome|||May form a homodimer, each monomer is composed of a chain A and a chain B.|||Putative phospholipase.|||The maturation cleavages that produces chains A and B are required to open the putative substrate binding pocket. Both chains A and B remain associated in the mature protein (By similarity). http://togogenome.org/gene/10090:Timp2 ^@ http://purl.uniprot.org/uniprot/Q6PI17|||http://purl.uniprot.org/uniprot/Q8BSJ3 ^@ Similarity ^@ Belongs to the protease inhibitor I35 (TIMP) family. http://togogenome.org/gene/10090:Try4 ^@ http://purl.uniprot.org/uniprot/Q9R0T7 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by autocatalytic cleavage (PubMed:23814066). Cleavage by CTRC inhibits autoactivation (PubMed:23814066).|||Belongs to the peptidase S1 family.|||Binds 1 Ca(2+) ion per subunit.|||Expressed in the pancreas, lung and kidney.|||Proteolytically cleaved and activated by an autocatalytic mechanism (PubMed:23814066). Cleavage by CTRC inhibits autoactivation (PubMed:23814066).|||Serine protease capable of autoactivation.|||extracellular space http://togogenome.org/gene/10090:Antxr2 ^@ http://purl.uniprot.org/uniprot/Q3TCL6|||http://purl.uniprot.org/uniprot/Q6DFX2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATR family.|||Binds laminin, and possibly also collagen type IV.|||Membrane|||Necessary for cellular interactions with laminin and the extracellular matrix. http://togogenome.org/gene/10090:Clasp1 ^@ http://purl.uniprot.org/uniprot/A0A087WQ31|||http://purl.uniprot.org/uniprot/A0A087WQF1|||http://purl.uniprot.org/uniprot/A0A087WS18|||http://purl.uniprot.org/uniprot/A5D6Q8|||http://purl.uniprot.org/uniprot/E9Q6L0|||http://purl.uniprot.org/uniprot/E9QKH0|||http://purl.uniprot.org/uniprot/Q80TV8 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CLASP family.|||Highly expressed in brain and heart and at lower levels in kidney, lung, skeletal muscle and testis.|||Interacts with ERC1, MAPRE1, MAPRE3, microtubules, and PHLDB2. The interaction with ERC1 may be mediated by PHLDB2. Interacts with GCC2; recruits CLASP1 to Golgi membranes (By similarity). Interacts with CLIP2 and RSN. Interacts with MACF1.|||Intron retention.|||Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules. Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2. This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (By similarity).|||centrosome|||cytoskeleton|||kinetochore|||spindle|||trans-Golgi network http://togogenome.org/gene/10090:Ceacam18 ^@ http://purl.uniprot.org/uniprot/Q9D871 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. CEA family.|||Membrane|||Mostly expressed in the small and large intestine and at lower levels also in other organs. http://togogenome.org/gene/10090:Polg ^@ http://purl.uniprot.org/uniprot/Q3UG70|||http://purl.uniprot.org/uniprot/Q3UZX3|||http://purl.uniprot.org/uniprot/Q75WC0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-A family.|||Heterotrimer composed of a catalytic subunit and a homodimer of accessory subunits.|||Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Grm8 ^@ http://purl.uniprot.org/uniprot/B7ZMR4|||http://purl.uniprot.org/uniprot/P47743|||http://purl.uniprot.org/uniprot/Q05BD6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.|||Interacts with PICK1.|||Membrane|||Strongly expressed in olfactory bulb, accessory olfactory bulb, and mammillary body. Weaker expression in the retina, and in scattered cells in the cortex and hindbrain. http://togogenome.org/gene/10090:Chst11 ^@ http://purl.uniprot.org/uniprot/B7ZMT9|||http://purl.uniprot.org/uniprot/B9EHC3|||http://purl.uniprot.org/uniprot/Q9JME2 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 2 family.|||By BMP2, suggesting it is a target of BMP signaling.|||Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Can also sulfate Gal residues in desulfated dermatan sulfate. Preferentially sulfates in GlcA->GalNAc unit than in IdoA->GalNAc unit. Does not form 4, 6-di-O-sulfated GalNAc when chondroitin sulfate C is used as an acceptor.|||First expressed at day 9.75 of embryogenesis in the apical ectodermal ridge (AER) of the developing limb buds and at the edges of branchial arches 1 and 2. Also expressed in the ventral neural tube, notochord and sympathetic ganglia and the mesonephric tubules of the developing kidneys. In the heart, it is expressed in the myocardium of the atrium and in the endocardial cushions of both the developing inflow tract and the atrioventricular valves. At day 15, it is expressed in the cartilage of developing bones, in vertebrae and cartilage of the trachea as well as in the thymus. In the forelimb, it is expressed in all developing bones, but absent from developing joint regions and was down-regulated in chondrocytes beginning to undergo mineralization, such as in the center of the ulna. At day 15, no expression in the neural tube is observed. In the heart at day 15, it is still expressed in the atrial valve, the atrioventricular valves and in the myocardium of the atrium, while in the kidney, it is expressed in the collecting tubules as well as in Bowman capsule. Interestingly, the liver displays a punctate expression at day 15. Also expressed in tooth primordia, hair follicles and mammary glands.|||Golgi apparatus membrane|||Membrane|||N-glycosylated; required for activity and stability.|||Predominantly expressed in brain and kidney. Also expressed at weaker level in heart, spleen and lung. Expressed in developing chondrocytes. http://togogenome.org/gene/10090:Pigyl ^@ http://purl.uniprot.org/uniprot/P0C1P0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts directly with PIGA; this interaction regulates glycosylphosphatidylinositol-N-acetylglucosaminyltransferase activity. Does not interact with Ras proteins.|||Endoplasmic reticulum membrane|||Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. May act by regulating the catalytic subunit PIGA. http://togogenome.org/gene/10090:Ces3a ^@ http://purl.uniprot.org/uniprot/Q63880 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Endoplasmic reticulum lumen|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. http://togogenome.org/gene/10090:Dnajc18 ^@ http://purl.uniprot.org/uniprot/Q9CZJ9 ^@ Subcellular Location Annotation ^@ Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Mak ^@ http://purl.uniprot.org/uniprot/Q04859 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated on serine and threonine residues (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors. Could have an important function in sensory cells and in spermatogenesis. May participate in signaling pathways used in visual and olfactory sensory transduction. Phosphorylates FZR1 in a cell cycle-dependent manner. Plays a role in the transcriptional coactivation of AR (By similarity).|||In pre- and postmeiotic male germ cells in testis. In photoreceptor cells of the retina and in the olfactory receptors, and in certain epithelia of the respiratory tract and choroid plexus (brain).|||Interacts with AR and CDK20. Found in a complex containing MAK, AR and NCOA3. Interacts with FZR1 (via WD repeats) (By similarity). Interacts with RP1.|||Mice are mostly fertile, develop normally, and exhibit no gross abnormalities and spermatogenesis is intact. However, both sperm motility and litter size is reduced.|||Midbody|||Nucleus|||On day 14 or 17 of embryonic development. Expression is observed in germ cells at the stages of late pachytene spermatocytes through to early round spermatids.|||Photoreceptor inner segment|||centrosome|||photoreceptor outer segment|||spindle http://togogenome.org/gene/10090:Gm20807 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXX7 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Fst ^@ http://purl.uniprot.org/uniprot/P47931 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Binds directly to activin and functions as an activin antagonist. Specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (FSH).|||Embryonic expression first occurs in the primitive streak, followed by expression in head mesoderm, somites, and specific rhombomeres of the hindbrain, and later in midbrain and diencephalon. No expression is seen in the node or notochord.|||Induces muscle hypertrophy when injected into the tibialis anterior muscle with reduced response in older mice.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Rbm12b1 ^@ http://purl.uniprot.org/uniprot/Q80YR9 ^@ Sequence Caution ^@ Possible contaminating sequence. The N-terminal 4 residues do not match the underlying genomic sequence. http://togogenome.org/gene/10090:Dsel ^@ http://purl.uniprot.org/uniprot/Q0VBN2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the dermatan-sulfate isomerase family.|||Membrane http://togogenome.org/gene/10090:Plekhf1 ^@ http://purl.uniprot.org/uniprot/Q3TB82 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Lysosome|||May induce apoptosis through the lysosomal-mitochondrial pathway. Translocates to the lysosome initiating the permeabilization of lysosomal membrane (LMP) and resulting in the release of CTSD and CTSL to the cytoplasm. Triggers the caspase-independent apoptosis by altering mitochondrial membrane permeabilization (MMP) resulting in the release of PDCD8 (By similarity).|||Nucleus|||PH and FYVE-type zinc finger domains are required for lysosomal location.|||Widely expressed.|||perinuclear region http://togogenome.org/gene/10090:Dand5 ^@ http://purl.uniprot.org/uniprot/Q3UPN3|||http://purl.uniprot.org/uniprot/Q76LW6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ At 7.0 dpc (early head-fold stage) expressed in perinodal region. At 7.5 dpc (late head-fold stage) expression begins to decrease in intensity on the left side and starts to be asymmetrically up-regulated on the right side of the node. By early 8.0 dpc (somitogenesis), highly expressed in the right side of the node. No expression seen in later stages of development.|||Belongs to the DAN family.|||Mice display multiple laterality defects including randomization of the L/R axis, left pulmonary isomerism thoracic situs inversus and cardiovascular malformations.|||Secreted|||Seems to play a role in the correct specification of the left-right axis. May antagonize NODAL and BMP4 signaling. Cystine knot-containing proteins play important roles during development, organogenesis, and tissue growth and differentiation. http://togogenome.org/gene/10090:Gen1 ^@ http://purl.uniprot.org/uniprot/Q8BMI4 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the XPG/RAD2 endonuclease family. GEN subfamily.|||Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.|||Endonuclease which resolves Holliday junctions (HJs) by the introduction of symmetrically related cuts across the junction point, to produce nicked duplex products in which the nicks can be readily ligated. Four-way DNA intermediates, also known as Holliday junctions, are formed during homologous recombination and DNA repair, and their resolution is necessary for proper chromosome segregation. Cleaves HJs by a nick and counter-nick mechanism involving dual coordinated incisions that lead to the formation of ligatable nicked duplex products. Cleavage of the first strand is rate limiting, while second strand cleavage is rapid. Largely monomeric, dimerizes on the HJ and the first nick occurs upon dimerization at the junction. Efficiently cleaves both single and double HJs contained within large recombination intermediates. Exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA. Has also endonuclease activity on 5'-flap and replication fork (RF) DNA substrates.|||Expressed in bone marrow and testis and to a lesser extent in thymus, spleen, brain and colon.|||Largely monomeric, dimerizes on the Holliday junction and the first nick occurs upon dimerization at the junction.|||Nucleus|||XPG-N, XPG-I,5'-3' exonuclease domains interact with DNA. Contains a chromodomain that acts as additional DNA interaction site and is required for efficient DNA recognition and cleavage. http://togogenome.org/gene/10090:Antkmt ^@ http://purl.uniprot.org/uniprot/Q501J2|||http://purl.uniprot.org/uniprot/Q91VW0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ANT/ATPSC lysine N-methyltransferase family.|||Mitochondrial protein-lysine N-methyltransferase that trimethylates adenine nucleotide translocases ANT2/SLC25A5 and ANT3/SLC25A6, thereby regulating mitochondrial respiration. Probably also trimethylates ANT1/SLC25A4.|||Mitochondrion membrane|||The pre-methyltransferase (preMT) region is responsible for mitochondrial localization. http://togogenome.org/gene/10090:Vmn1r52 ^@ http://purl.uniprot.org/uniprot/Q9EP79 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Czib ^@ http://purl.uniprot.org/uniprot/Q8BHG2 ^@ Domain|||Similarity|||Subunit ^@ Belongs to the UPF0587 family.|||Monomer.|||The N-terminal and the C-terminal half of the protein have a very similar 3D-structure, suggesting they arose from duplication. Requires a bound zinc ion for normal folding and solubility. http://togogenome.org/gene/10090:Tbc1d2 ^@ http://purl.uniprot.org/uniprot/B1AVH7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as GTPase-activating protein for RAB7A. Signal effector acting as a linker between RAC1 and RAB7A, leading to RAB7A inactivation and subsequent inhibition of cadherin degradation and reduced cell-cell adhesion (By similarity).|||Cell junction|||Cytoplasm|||Cytoplasmic vesicle|||Interacts with activated RAC1 and CDH1. http://togogenome.org/gene/10090:H2bc23 ^@ http://purl.uniprot.org/uniprot/P10853|||http://purl.uniprot.org/uniprot/Q8CBB6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Dram2 ^@ http://purl.uniprot.org/uniprot/Q9CR48|||http://purl.uniprot.org/uniprot/Q9D835 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the DRAM/TMEM150 family.|||Expressed in the retina.|||Lysosome membrane|||Membrane|||Photoreceptor inner segment|||Plays a role in the initiation of autophagy. In the retina, might be involved in the process of photoreceptor cells renewal and recycling to preserve visual function. Induces apoptotic cell death when coexpressed with DRAM1. http://togogenome.org/gene/10090:Bbof1 ^@ http://purl.uniprot.org/uniprot/Q3V079 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Basal body protein required in multiciliate cells to align and maintain cilia orientation in response to flow. May act by mediating a maturation step that stabilizes and aligns cilia orientation. Not required to respond to planar cell polarity (PCP) or flow-based orientation cues (By similarity).|||Belongs to the BBOF1 family.|||cilium basal body http://togogenome.org/gene/10090:Siah1b ^@ http://purl.uniprot.org/uniprot/A2AHZ2|||http://purl.uniprot.org/uniprot/Q06985 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SINA (Seven in absentia) family.|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes.|||Homodimer.|||Induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response.|||Nucleus|||Phosphorylated on Ser-19 by ATM and ATR.|||The RING-type zinc finger domain is essential for ubiquitin ligase activity.|||The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.|||The SBD domain (substrate-binding domain) mediates the interaction with substrate proteins. It is related to the TRAF family.|||Widely expressed at low level in embryos and adults. Due to the high similarity between SIAH1A and SIAH1B, it is difficult to distinguish its own tissue specificity. Overexpressed in endothelial cells of adult lung. http://togogenome.org/gene/10090:Prom2 ^@ http://purl.uniprot.org/uniprot/Q3UUY6 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the prominin family.|||Binds cholesterol.|||Expressed in kidney and testis. Present in urine within small membrane particles (at protein level). In the submandibular gland, expressed in seromucous acini. In the parotid gland, expressed in the serous acini and in all segments of the duct system. In the sublingual gland, expressed in large excretory ducts, but absent in intercalated ducts. In the extraorbital lacrimal gland, expressed in the serous acini. In the eyelid, expressed in the acini of the meibomian gland.|||Glycosylated.|||cilium membrane|||microvillus membrane http://togogenome.org/gene/10090:Vtn ^@ http://purl.uniprot.org/uniprot/P29788 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with SERPINE1/PAI1, insulin and C1QBP.|||It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.|||N- and O-glycosylated.|||Plasma.|||Sulfated on tyrosine residues.|||The SMB domain mediates interaction with SERPINE1/PAI1. The heparin-binding domain mediates interaction with insulin (By similarity).|||Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway.|||extracellular space http://togogenome.org/gene/10090:Ranbp10 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0G4|||http://purl.uniprot.org/uniprot/A9UGK3|||http://purl.uniprot.org/uniprot/Q6VN19 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RANBP9/10 family.|||Cytoplasm|||Expressed at highest levels in spleen and liver. Expressed in megakaryocytes and platelets (at protein level).|||May act as an adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (By similarity). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for RAN GTPase (PubMed:18347012). May play an essential role in hemostasis and in maintaining microtubule dynamics with respect to both platelet shape and function (PubMed:19801445).|||May form homodimers. Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with RAN and RANBP9. Interacts with the HGF receptor MET. Interacts with AR (By similarity). Interacts with TUBB1 (PubMed:18347012). Interacts with YPEL5 (By similarity). May interact with TUBB5 (PubMed:18347012). Interacts with DDX4 (PubMed:27622290).|||Mutant mice are viable and show no conspicuous phenotype. They have normal platelet counts and only slightly reduced proplatelet formation. Resting platelets tend to have a more spherical shape. Many platelets exhibit disorders in microtubule filament numbers and localization. The animals show a markedly prolonged bleeding time. Granule release is also reduced.|||Nucleus|||The SPRY domain mediates the interaction with MET. http://togogenome.org/gene/10090:Gpr132 ^@ http://purl.uniprot.org/uniprot/Q9Z282 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By DNA-damaging agents.|||Cell membrane|||Highly expressed in hematopoietic tissues rich in lymphocytes like spleen and thymus. Weakly expressed in heart and lung. Highly expressed in infiltrating macrophages within atherosclerotic lesions.|||May be a receptor for oxidized free fatty acids derived from linoleic and arachidonic acids such as 9-hydroxyoctadecadienoic acid (9-HODE). Activates a G alpha protein, most likely G alpha(q). May be involved in apoptosis. Functions at the G2/M checkpoint to delay mitosis. May function as a sensor that monitors the oxidative states and mediates appropriate cellular responses such as secretion of paracrine signals and attenuation of proliferation. May mediate ths accumulation of intracellular inositol phosphates at acidic pH through proton-sensing activity (By similarity). http://togogenome.org/gene/10090:B3gnt4 ^@ http://purl.uniprot.org/uniprot/Q1RLK6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Has activity for type 2 oligosaccharides.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Lce3c ^@ http://purl.uniprot.org/uniprot/Q91V05 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Aifm3 ^@ http://purl.uniprot.org/uniprot/Q3TY86 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAD-dependent oxidoreductase family.|||Induces apoptosis through a caspase dependent pathway. Reduces mitochondrial membrane potential (By similarity).|||May be due to intron retention.|||Mitochondrion|||The Rieske domain induces apoptosis. http://togogenome.org/gene/10090:Bpgm ^@ http://purl.uniprot.org/uniprot/P15327 ^@ Activity Regulation|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ At alkaline pH BPGM favors the synthase reaction; however, at lower pH the phosphatase reaction is dominant. Inhibited by citrate.|||Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.|||Expressed in red blood cells. Expressed in placenta (labyrinthine trophoblasts).|||Homodimer.|||Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.11) activity. http://togogenome.org/gene/10090:Avpr1a ^@ http://purl.uniprot.org/uniprot/Q3U1H9|||http://purl.uniprot.org/uniprot/Q62463 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.|||Cell membrane|||Knockout mice display deficits in individual discrimination. Male mice lacking functional AVPR1A (V1aRKO) exhibit markedly reduced anxiety-like behavior and a profound impairment in social recognition. V1aRKO performed normally on spatial and non-social olfactory learning and memory tasks.|||Membrane|||Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system.|||Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system. Involved in social memory formation. http://togogenome.org/gene/10090:Serpinb5 ^@ http://purl.uniprot.org/uniprot/P70124 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Interacts with IRF6.|||Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity (By similarity).|||extracellular space http://togogenome.org/gene/10090:Itgav ^@ http://purl.uniprot.org/uniprot/P43406 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-V (ITGAV) associates with either beta-1 (ITGB1), beta-3 (ITGB3), beta-5 (ITGB5), beta-6 (ITGB6) or beta-8 (ITGB8) (Probable). Interacts with RAB25. Interacts with CIB1 (By similarity). Integrins ITGAV:ITGB3 and ITGAV:ITGB5 interact with FBLN5 (via N-terminus) (PubMed:11805835). ITGAV:ITGB3 and ITGAV:ITGB5 interact with CCN3 (By similarity). ITGAV:ITGB3 interacts with ADGRA2 (By similarity). ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors (By similarity). ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1. ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3. ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1. ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R (By similarity). ITGAV:ITGB3 interacts with IGF2 (By similarity). ITGAV:ITGB3 and ITGAV:ITGB6 interact with FBN1 (By similarity). ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain) (By similarity). ITGAV:ITGB6 interacts with TGFB1 (PubMed:10025398). ITGAV:ITGB3 interacts with PTN. Forms a complex with PTPRZ1 and PTN that stimulates endothelial cell migration through ITGB3 'Tyr-773' phosphorylation (By similarity).|||Mice expressing a null mutation of the alpha-V subunit gene survive until late in embryonic development and occasionally even to birth. They demonstrate cleft palate, and defective development of CNS and gastrointestinal blood vessels.|||The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, TGFB1 and vWF (PubMed:9827803, PubMed:10025398). They recognize the sequence R-G-D in a wide array of ligands. Alpha-V integrins may play a role in embryo implantation, angiogenesis and wound healing (PubMed:9827803). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (By similarity). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (By similarity). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (By similarity). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (By similarity). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (By similarity). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (By similarity). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (By similarity). ITGAV:ITGB3 and ITGAV:ITGB6 act as a receptor for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1 (By similarity). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:10025398, PubMed:25127859). ITGAV:ITGB3 acts as a receptor for CD40LG (By similarity). ITGAV:ITGB3 binds to the Lilrb4a/Gp49b receptor and enhances the Lilrb4a-mediated inhibition of mast cell activation (PubMed:11323698). ITGAV:ITGB3 also suppresses marginal zone B cell antibody production through its interaction with Lilrb4a (PubMed:24935931).|||focal adhesion http://togogenome.org/gene/10090:Or1e1f ^@ http://purl.uniprot.org/uniprot/Q8VEZ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Taf6l ^@ http://purl.uniprot.org/uniprot/H3BJR2|||http://purl.uniprot.org/uniprot/H3BK01|||http://purl.uniprot.org/uniprot/Q8R2K4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF6 family.|||Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex (By similarity). With TAF5L, acts as an epigenetic regulator essential for somatic reprogramming. Regulates target genes through H3K9ac deposition and MYC recruitment which trigger MYC regulatory network to orchestrate gene expression programs to control embryonic stem cell state (PubMed:31005419). Functions with MYC to activate target gene expression through RNA polymerase II pause release (PubMed:31005419).|||Nucleus|||The PCAF complex is composed of a number of TBP-associated factors (TAFS), such as TAF5, TAF5L, TAF6, TAF6L, TAF9, TAF10 and TAF12, PCAF, and also PCAF-associated factors (PAFs), such as TADA2L/ADA2, TADA3L/ADA3 and SPT3 (By similarity). Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. http://togogenome.org/gene/10090:Mos ^@ http://purl.uniprot.org/uniprot/P00536 ^@ Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Expressed specifically in testis during spermatogenesis. http://togogenome.org/gene/10090:Sertad2 ^@ http://purl.uniprot.org/uniprot/Q9JJG5 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. May act as coactivator as well as corepressor of E2F1-TFDP1 and E2F4-TFDP1 complexes on E2F consensus binding sites, which would activate or inhibit E2F-target genes expression. Modulates fat storage by down-regulating the expression of key genes involved in adipocyte lipolysis, thermogenesis and oxidative metabolism.|||Cytoplasm|||Expressed in white and brown adipose tissue.|||Interacts with XPO1; which mediates nuclear export. Interacts with TFDP1; modulates transactivation activity of TFDP1/E2F complexes (By similarity).|||Nucleus|||Polyubiquitinated, which promotes proteasomal degradation.|||Resist development of obesity because of enhanced lipolysis and thermogenesis due, in part, to an increase in brown adipocytes number. On high fat diet (HFD), show reduced white adipose tissue (WAT) weight with smaller adipocyte size, improved glucose tolerance and insulin sensitivity with lower fasting glucose and insulin concentrations. Animals on HFD have higher and lower concentrations of adiponectin and leptin, respectively, compared to wild-type. They don't develop liver steatosis and have 57% less adipose tissue macrophage infiltration.|||Up-regulated by high fat diet in adipose tissue. http://togogenome.org/gene/10090:Evi2a ^@ http://purl.uniprot.org/uniprot/P20934 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the EVI2A family.|||Expression of this gene is altered by viral integration and this altered expression may predispose cells to myeloid disease (PubMed:2167436).|||May complex with itself or/and other proteins within the membrane, to function as part of a cell-surface receptor.|||Membrane http://togogenome.org/gene/10090:Fbxo17 ^@ http://purl.uniprot.org/uniprot/Q9QZM8 ^@ Function|||Subunit|||Tissue Specificity ^@ Expressed primarily in the brain.|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with SKP1 and CUL1 (By similarity).|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Able to recognize and bind denatured glycoproteins, which are modified with complex-type oligosaccharides. Also recognizes sulfated glycans. Does not bind high-mannose glycoproteins (By similarity). http://togogenome.org/gene/10090:Arhgap6 ^@ http://purl.uniprot.org/uniprot/O54834 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in retina and lung.|||GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Could regulate the interactions of signaling molecules with the actin cytoskeleton. Promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology (By similarity). http://togogenome.org/gene/10090:Triqk ^@ http://purl.uniprot.org/uniprot/B2B9E1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRIQK family.|||Endoplasmic reticulum membrane|||Expressed in embryo from 7 to 17 dpc.|||Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||May play a role in cell growth and maintenance of cell morphology. http://togogenome.org/gene/10090:Vwa8 ^@ http://purl.uniprot.org/uniprot/Q8CC88 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Exhibits ATPase activity in vitro.|||Isoform 1 is predominantly expressed in liver, kidney, pancreas, heart, and skeletal muscle (at protein level).|||Mitochondrion|||Monomer (By similarity). Interacts with PEX7. Interacts with PEX5 in a PEX7-dependent manner (By similarity).|||Up-regulated by high fat diet (at protein level). http://togogenome.org/gene/10090:Igflr1 ^@ http://purl.uniprot.org/uniprot/Q3U4N7 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Probable cell membrane receptor for the IGF-like family protein IGFL.|||Ubiquitously expressed with higher expression in lymph node. Highly expressed in T-cells and monocytes. http://togogenome.org/gene/10090:Pank1 ^@ http://purl.uniprot.org/uniprot/Q8K4K6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type II pantothenate kinase family.|||Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis (PubMed:20559429, PubMed:22815849). Required for the hepatic CoA increase during the switch from glucose to fatty acid oxidation that occurs in the fasting state (PubMed:20559429).|||Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.|||Cytoplasm|||Highly expressed in the liver (PubMed:10625688, PubMed:20559429, PubMed:16040613). Expressed at lower levels in the kidney (PubMed:10625688).|||Highly expressed in the liver, heart and kidney.|||Homodimer.|||Nucleus|||Pank1 single knockout mice exhibit reduced hepatic CoA levels, a reduced rate of CoA-dependent fatty acid oxidation in the fasting state, impaired gluconeogenesis, and mild hypoglycemia in the fasting state (PubMed:20559429). Show a reduction in pantothenate kinase (PANK) activity of about 50% and 40% in the liver and brain respectively (PubMed:22815849). Pank1 and Pank2 double knockout mice develop progressively severe hypoglycemia and hyperketonemia by postnatal day 10 leading to their death by day 17 (PubMed:22815849). A reduction in PANK activity of about 90-95% seen in the liver and brain and hepatocytes show reduced levels of NADH (PubMed:22815849).|||Recycling endosome|||Strongly inhibited by acetyl-CoA and modestly by malonyl-CoA (PubMed:16040613, PubMed:10625688, PubMed:12095677). Refractory to inhibition by both CoA and palmitoyl-CoA (PubMed:16040613). Inhibited by calcium hopantenate (PubMed:17379144).|||Strongly inhibited by non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA (PubMed:12095677). Also inhibited by palmitoyl CoA (PubMed:12095677). Inhibited by calcium hopantenate (PubMed:17379144).|||The N-terminal extension, may be the regulatory domain.|||clathrin-coated vesicle|||nucleolus http://togogenome.org/gene/10090:Rrm2 ^@ http://purl.uniprot.org/uniprot/P11157 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ribonucleoside diphosphate reductase small chain family.|||Binds 2 iron ions per subunit.|||Cytoplasm|||Heterodimer of a large and a small subunit. Interacts (via Cy motif and when phosphorylated at Thr-33) with CCNF; the interaction occurs exclusively in G2 and early M (By similarity).|||Nucleus|||Phosphorylation on Ser-20 relieves the inhibitory effect on Wnt signaling (By similarity). Phosphorylated on Thr-33 by CDK1 and CDK2; predominantly in G2 and M phase (By similarity).|||Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling (By similarity).|||Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2.|||Ubiquitinated by the SCF(CCNF) E3 ubiquitin-protein ligase complex; leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Ndufa7 ^@ http://purl.uniprot.org/uniprot/Q9Z1P6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA7 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Suclg1 ^@ http://purl.uniprot.org/uniprot/Q9WUM5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the succinate/malate CoA ligase alpha subunit family.|||Heterodimer of an alpha and a beta subunit. Different beta subunits determine nucleotide specificity. Together with the ATP-specific beta subunit SUCLA2, forms an ADP-forming succinyl-CoA synthetase (A-SCS). Together with the GTP-specific beta subunit SUCLG2 forms a GDP-forming succinyl-CoA synthetase (G-SCS).|||Mitochondrion|||Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and specificity for either ATP or GTP is provided by different beta subunits. http://togogenome.org/gene/10090:Hnrnpa3 ^@ http://purl.uniprot.org/uniprot/Q0VG47|||http://purl.uniprot.org/uniprot/Q3UZG3|||http://purl.uniprot.org/uniprot/Q5FB19|||http://purl.uniprot.org/uniprot/Q5U3M2|||http://purl.uniprot.org/uniprot/Q8BG05 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Identified in the spliceosome C complex.|||Nucleus|||Plays a role in cytoplasmic trafficking of RNA. Binds to the cis-acting response element, A2RE. May be involved in pre-mRNA splicing (By similarity). http://togogenome.org/gene/10090:Dyrk1b ^@ http://purl.uniprot.org/uniprot/Q9Z188 ^@ Activity Regulation|||Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.|||Chromosome|||Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and TCF1/HNF1A. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interacts with DCAF7. Interacts with RNF169.|||Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:12633499). Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenance. During DNA damage, mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2. Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase catalytic subunit 1 (G6PC1).|||Inactive.|||Inhibited by RANBP9.|||Isoform 1 and isoform 2 are broadly expressed. Isoform 3 seems specific for skeletal muscle (at protein level).|||Isoform 1 is present from 14 dpc. Isoform 3 is present from 18 dpc (at protein level).|||Nucleus|||Phosphorylated by MAP kinase. Tyrosine phosphorylation may be required for dimerization (By similarity).|||nucleolus http://togogenome.org/gene/10090:Phf10 ^@ http://purl.uniprot.org/uniprot/K4DI61|||http://purl.uniprot.org/uniprot/Q9D8M7 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAYP family.|||Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Interacts with ACTL6A/BAF53A, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A and PBRM1/BAF180.|||Expressed in neural cells at 10.5-11.5 dpc. At 10.5 to 16.5 dpc, in the developing spinal cord, specifically expressed in proliferating neural progenitors of the ventricular zone. In the developing forebrain and cerebellar primordium, expression is restricted to proliferating neuroepithelial progenitors and cerebellar granule precursors.|||Involved in transcription activity regulation by chromatin remodeling. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.|||It is uncertain whether Met-1 or Met-88 is the initiator.|||Nucleus|||Widely expressed. Expressed selectively in neural stem and progenitor cells (at protein level). http://togogenome.org/gene/10090:Cttn ^@ http://purl.uniprot.org/uniprot/Q60598 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated.|||Cell junction|||Cell membrane|||Cell projection|||Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:17403031). Plays a role in the formation of lamellipodia and in cell migration (By similarity). Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (PubMed:22262902). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (By similarity). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (By similarity).|||Endoplasmic reticulum|||Expressed in most tissues, except in B-lymphocytes or plasma cells.|||Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (By similarity). Interacts (via N-terminus) with NEDD9 (PubMed:24574519). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Forms a complex with ABL1 and MYLK (By similarity). Interacts with SHANK2 and SHANK3 (via its SH3 domain). Interacts with PLXDC2 and SRCIN1. Interacts with SAMSN1 (via SH3 domain). Interacts (via SH3 domain) with ASAP1 (via Pro-rich region). Interacts (via SH3 domain) with DNM2. Interacts with ACTN1 (By similarity). Interacts with FER. Interacts with KCNA2 (via non-phosphorylated C-terminus). Interacts with FGD1. Interacts with ABL2 (PubMed:22297987). Interacts with CTTNBP2NL; this interaction may target CTTN to stress fibers. Interacts with CTTNBP2; this interaction may target CTTN at the cell cortex or dendritic spines. Interacts with KCNH1 (By similarity). Interacts (via SH3 domain) with DIP2A (via N-terminus); the interaction enhances CTTN acetylation and is required for proper synaptic transmission (PubMed:31600191).|||Phosphorylated by FER. Phosphorylated in response to FGR activation (PubMed:7693700). Phosphorylation by SRC promotes MYLK binding (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation (By similarity). Phosphorylated by PTK2/FAK1 in response to cell adhesion (By similarity). Tyrosine phosphorylation in transformed cells may contribute to cellular growth regulation and transformation. Phosphorylated by PKN2 at both serine and threonine residues in a GTP-bound Rac1-dependent manner in hyaluronan-induced astrocytes and hence down-regulated CTTN ability to associate with filamentous actin.|||The SH3 motif may mediate binding to the cytoskeleton.|||cell cortex|||clathrin-coated pit|||cytoskeleton|||dendrite|||dendritic spine|||focal adhesion|||lamellipodium|||podosome|||ruffle http://togogenome.org/gene/10090:Cnih2 ^@ http://purl.uniprot.org/uniprot/O35089|||http://purl.uniprot.org/uniprot/Q3SYI8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with GRIA1 (By similarity). Interacts with CACGN8.|||Belongs to the cornichon family.|||Brain. Highest levels seen in the hippocampus, intermediate levels in the cerebral cortex, striatum olfactory bulb, and thalamus and lower levels in the cerebellum (at protein level). Also expressed in the lung.|||Endoplasmic reticulum membrane|||First detected at the eight-cell stage. Expressed in eight-cell embryo, blastocyst, 6.5-day whole embryo, 7.5-day primitive streak, 11.5-day limb bud and in 13.5-day whole embryo.|||Membrane|||Postsynaptic cell membrane|||Postsynaptic density|||Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by regulating their rates of activation, deactivation and desensitization. Blocks CACNG8-mediated resensitization of AMPA receptors.|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Dip2b ^@ http://purl.uniprot.org/uniprot/Q3UH60 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DIP2 family.|||Excessive axonal outgrowth and branching with decreased dendritic outgrowth (PubMed:32153366). Reduced acetylation of alpha-tubulin (PubMed:32153366).|||Highly expressed in brain and spinal cord (at protein level) (PubMed:32153366). In brain, expression is detected in the main olfactory bulb, cortex, lateral ventricle, cornu ammonis 1, cornu ammonis 3, dentate gyrus, striatum, cerebellar cortex and medial habenula (PubMed:32153366). Expressed primarily in neurons including excitatory pyramidal neurons and inhibitory interneurons (PubMed:32153366).|||In the embryo, expression initiates at 15.5 dpc in both the neocortex and hippocampus.|||Interacts with alpha-tubulin.|||Negatively regulates axonal outgrowth and is essential for normal synaptic transmission (PubMed:32153366). Not required for regulation of axon polarity (PubMed:32153366). Promotes acetylation of alpha-tubulin (PubMed:32153366).|||Perikaryon|||axon|||dendrite http://togogenome.org/gene/10090:Fabp7 ^@ http://purl.uniprot.org/uniprot/P51880 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ B-FABP could be involved in the transport of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development. It is required for the establishment of the radial glial fiber system in developing brain, a system that is necessary for the migration of immature neurons to establish cortical layers.|||Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Expressed in brain and other neural tissues.|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. http://togogenome.org/gene/10090:Dcakd ^@ http://purl.uniprot.org/uniprot/Q8BHC4 ^@ Similarity ^@ Belongs to the CoaE family. http://togogenome.org/gene/10090:H2ac19 ^@ http://purl.uniprot.org/uniprot/B2RWH3|||http://purl.uniprot.org/uniprot/Q6GSS7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Tnfrsf17 ^@ http://purl.uniprot.org/uniprot/O88472 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6.|||Detected in spleen, thymus, bone marrow and heart, and at lower levels in kidney and lung.|||Membrane|||Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK (By similarity). http://togogenome.org/gene/10090:Cd52 ^@ http://purl.uniprot.org/uniprot/Q3U1T8|||http://purl.uniprot.org/uniprot/Q64389 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed on lymphohematopoietic tissues, including thymus, spleen, and bone marrow, but not in liver, kidney, and brain.|||May play a role in carrying and orienting carbohydrate, as well as having a more specific role.|||Membrane http://togogenome.org/gene/10090:Ppp1r27 ^@ http://purl.uniprot.org/uniprot/Q9D119 ^@ Function|||Subunit ^@ Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.|||Interacts with DYSF and PPP1CA. http://togogenome.org/gene/10090:Lifr ^@ http://purl.uniprot.org/uniprot/P42703|||http://purl.uniprot.org/uniprot/Q3UKU5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Cell membrane|||Heterodimer composed of LIFR and IL6ST. The heterodimer formed by LIFR and IL6ST interacts with the complex formed by CNTF and CNTFR (By similarity).|||Membrane|||Placenta, liver, kidney, heart, lung, brain, and embryos. The liver may be the primary site of synthesis of the secreted form.|||Secreted|||Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Iftap ^@ http://purl.uniprot.org/uniprot/Q9CQI4 ^@ Disruption Phenotype|||Function|||Subunit|||Tissue Specificity ^@ Interacts with IFT122; the interaction associates IFTAP with IFT-A complex.|||Mutant mice show no obvious anatomical abnormalities associated with ciliary dysfunction.|||Seems to play a role in ciliary BBSome localization, maybe through interaction with IFT-A complex.|||Ubiquitous. http://togogenome.org/gene/10090:Esm1 ^@ http://purl.uniprot.org/uniprot/Q9QYY7 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Involved in angiogenesis; promotes angiogenic sprouting. May have potent implications in lung endothelial cell-leukocyte interactions (By similarity).|||O-glycosylated; contains chondroitin sulfate and dermatan sulfate.|||Secreted http://togogenome.org/gene/10090:Arg2 ^@ http://purl.uniprot.org/uniprot/O08691 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the arginase family.|||Binds 2 manganese ions per subunit.|||Homotrimer.|||May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated CD4(+) and CD8(+) T cells (PubMed:27745970, PubMed:25009204). May suppress inflammation-related signaling in asthmatic airway epithelium (PubMed:27214549). May contribute to the immune evasion of H.pylori by restricting M1 macrophage activation and polyamine metabolism (PubMed:27074721). May play a role in promoting prenatal immune suppression (By similarity). Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction (PubMed:22928666). Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling (PubMed:25484082). Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Pms2 ^@ http://purl.uniprot.org/uniprot/P54279 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA mismatch repair MutL/HexB family.|||Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Possesses an ATPase activity, but in the absence of gross structural changes, ATP hydrolysis may not be necessary for proficient mismatch repair (By similarity).|||Heterodimer of PMS2 and MLH1 (MutL alpha); this interaction is required for the stability of both partners. Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MTMR15/FAN1.|||Nucleus http://togogenome.org/gene/10090:Mef2bl ^@ http://purl.uniprot.org/uniprot/K7N7F1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Disp2 ^@ http://purl.uniprot.org/uniprot/Q8CIP5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the dispatched family.|||Membrane http://togogenome.org/gene/10090:Kctd20 ^@ http://purl.uniprot.org/uniprot/Q8CDD8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with AKT1; AKT2 and AKT3 (PubMed:24156551). Interacts with PPP2CA and PPP1CA (PubMed:24156551). Part of a complex containing MARK4 (By similarity).|||Promotes the phosphorylation of AKT family members.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Ptpn7 ^@ http://purl.uniprot.org/uniprot/Q8BUM3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cytoplasm|||Expressed in bone marrow-derived mast cells.|||Inhibited upon FCER1A triggering.|||May play a role in the regulation of T and B-lymphocyte development and signal transduction.|||Oxidized at active site cysteine. Treatment with pervanadate (vanadate and H(2)O(2)) or with antigen enhanced oxidation of active site cysteine.|||cytoskeleton http://togogenome.org/gene/10090:Ist1 ^@ http://purl.uniprot.org/uniprot/Q9CX00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IST1 family.|||Cytoplasmic vesicle|||ESCRT-III-like protein involved in cytokinesis, nuclear envelope reassembly and endosomal tubulation (By similarity). Is required for efficient abscission during cytokinesis (By similarity). Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells (By similarity). During late anaphase, involved in nuclear envelope reassembly and mitotic spindle disassembly together with the ESCRT-III complex: IST1 acts by mediating the recruitment of SPAST to the nuclear membrane, leading to microtubule severing (By similarity). Recruited to the reforming nuclear envelope (NE) during anaphase by LEMD2 (By similarity). Regulates early endosomal tubulation together with the ESCRT-III complex by mediating the recruitment of SPAST (By similarity).|||Interacts with CHMP1A, CHMP1B, VPS4A and VTA1. Interacts with SPAST, STAMBP, and USP8. May interact with VPS37B. May associate with the ESCRT-I complex. Interacts with MITD1, in competition with VSP4. Interacts with SPART (via MIT domain); leading to the recruitment of SPART to midbodies. Interacts with SPAST.|||Midbody|||Nucleus envelope|||centrosome http://togogenome.org/gene/10090:Snrpf ^@ http://purl.uniprot.org/uniprot/P62307|||http://purl.uniprot.org/uniprot/Q497K3|||http://purl.uniprot.org/uniprot/Q6NZQ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2. Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP. Interacts with GEMIN2 (via N-terminus); the interaction is direct. Interacts with SNRPD2; the interaction is direct. Interacts with SNRPE; the interaction is direct.|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. As part of the U7 snRNP it is involved in histone 3'-end processing.|||cytosol http://togogenome.org/gene/10090:Shc2 ^@ http://purl.uniprot.org/uniprot/Q8BMC3 ^@ Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Expressed in brain. Expressed at high level in the hypothalamus and at low level in the caudate nucleus.|||Interacts with the Trk receptors in a phosphotyrosine-dependent manner and MEGF12. Once activated, binds to GRB2 (By similarity).|||Phosphorylated on tyrosine by the Trk receptors.|||Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons.|||The PID domain mediates binding to the TrkA receptor. http://togogenome.org/gene/10090:Eef2 ^@ http://purl.uniprot.org/uniprot/P58252 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.|||Binds to 80S ribosomes (PubMed:34815424). Actively translating ribosomes show mutually exclusive binding of eIF5a (EIF5A or EIF5A2) and EEF2/eEF2 (By similarity). Interacts with SERBP1; interaction sequesters EEF2/eEF2 at the A-site of the ribosome, thereby blocking the interaction sites of the mRNA-tRNA complex, promoting ribosome stabilization and hibernation (PubMed:34815424). Interacts with HABP4; interaction takes place at the A-site of hibernating ribosomes and promotes ribosome stabilization (By similarity). Component of the mRNA surveillance SURF complex, at least composed of ERF1, ERF3 (ERF3A or ERF3B), EEF2, UPF1/RENT1, SMG1, SMG8 and SMG9. Interacts with RBPMS2 (By similarity).|||Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome.|||Cytoplasm|||Diphthamide is 2-[3-carboxyamido-3-(trimethyl-ammonio)propyl]histidine (By similarity).|||ISGylated.|||Nucleus|||Phosphorylation by EF-2 kinase completely inactivates EF-2; it requires prior phosphorylation by CDK2 at Ser-595 during mitotic prometaphase (PubMed:34815424). Phosphorylation by CSK promotes SUMOylation, proteolytic cleavage, and nuclear translocation if the C-terminal fragment (By similarity).|||Proteolytically processed at two sites following phosphorylation by CSK.|||SUMOylated following phosphorylation by CSK, promotes proteolytic cleavage. http://togogenome.org/gene/10090:Zfp865 ^@ http://purl.uniprot.org/uniprot/Q3U3I9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Rab13 ^@ http://purl.uniprot.org/uniprot/Q9DD03 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Interacts (GTP-bound form) with MICALL2; competes with RAB8A and is involved in tight junctions assembly. Interacts (GTP-bound form) with MICALL1. Interacts (GTP-bound form) with MICAL1, MICAL3, MICALCL, EHBP1 and EHBP1L1; ternary complexes of RAB8A, RAB13 and either MICAL1 or EHBP1L1 are possible. Interacts with PRKACA; downstream effector of RAB13 involved in tight junction assembly. Interacts with GRB2; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts (isoprenylated form) with PDE6D; dissociates RAB13 from membranes. Interacts with BICDL2/BICDR2. Interacts with LEPROT and LEPROTL1.|||Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP). That Rab may be activated by DENND1C, a guanine exchange factor. Activated in response to insulin (By similarity).|||Recycling endosome membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in endocytic recycling and regulates the transport to the plasma membrane of transmembrane proteins like the tight junction protein OCLN/occludin. Thereby, it regulates the assembly and the activity of tight junctions. Moreover, it may also regulate tight junction assembly by activating the PKA signaling pathway and by reorganizing the actin cytoskeleton through the activation of the downstream effectors PRKACA and MICALL2 respectively. Through its role in tight junction assembly, may play a role in the establishment of Sertoli cell barrier. Plays also a role in angiogenesis through regulation of endothelial cells chemotaxis. Also involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore may play a role in glucose homeostasis.|||lamellipodium|||tight junction|||trans-Golgi network membrane http://togogenome.org/gene/10090:Mfge8 ^@ http://purl.uniprot.org/uniprot/P21956|||http://purl.uniprot.org/uniprot/Q3TDU5 ^@ Caution|||Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Contributes to phagocytic removal of apoptotic cells in many tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5 receptors. Also binds to phosphatidylserine-enriched cell surfaces in a receptor-independent manner. Zona pellucida-binding protein which may play a role in gamete interaction (By similarity). Plays an important role in the maintenance of intestinal epithelial homeostasis and the promotion of mucosal healing. Promotes VEGF-dependent neovascularization.|||Isoform 1 and isoform 2 are detectable in mammary tissue from non-pregnant animals, with isoform 2 being predominant. Levels of isoform 1 increase during gestation and lactation while levels of isoform 2 decrease.|||Isoform 1 is induced by insulin, prolactin and hydrocortisone in mammary epithelial cells. Expression of isoform 2 is repressed by the same treatment.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mammary epithelial cell surfaces and spermatozoan. Isoform 2 is present in brain, heart, kidney and spleen and at low levels in lung, liver, small intestine and testis.|||Membrane|||N-glycosylated. Isoform 1 also exists in both an O-glycosylated and a non-O-glycosylated form.|||Secreted|||The F5/8 type C 2 domain mediates high-affinity binding to phosphatidylserine-containing membranes.|||acrosome membrane http://togogenome.org/gene/10090:Foxc2 ^@ http://purl.uniprot.org/uniprot/B9EI61|||http://purl.uniprot.org/uniprot/Q61850 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation ^@ Expressed temporally in developing embryos, first in the non-notochordal mesoderm and later in areas of mesenchymal condensation in the trunk, head and limbs.|||Nucleus|||Phosphorylation regulates FOXC2 transcriptional activity by promoting its recruitment to chromatin.|||Transcriptional activator. Might be involved in the formation of special mesenchymal tissues. http://togogenome.org/gene/10090:Gm20805 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Mtx1 ^@ http://purl.uniprot.org/uniprot/A0A6I8MWZ8|||http://purl.uniprot.org/uniprot/Q8R5C0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the metaxin family.|||Membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Hyal5 ^@ http://purl.uniprot.org/uniprot/Q812F3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 56 family.|||Catalyzes the hydrolysis of hyaluronan into smaller oligosaccharide fragments (PubMed:16330764, PubMed:16925524, PubMed:19605784). Does not appear to be essential for fertilization (PubMed:19605784).|||Cell membrane|||Detected in the developing testis at postnatal day 20, with increasing levels through development.|||Expressed in testis, epididymal sperm and epididymides (at protein level) (PubMed:16330764, PubMed:19605784). Expressed at highest levels in testis with lesser amounts in epididymal sperm (PubMed:16925524, PubMed:16330764, PubMed:19605784).|||No visible phenotype. Viable and fertile.|||Secreted|||acrosome membrane http://togogenome.org/gene/10090:Slc7a1 ^@ http://purl.uniprot.org/uniprot/Q09143|||http://purl.uniprot.org/uniprot/Q3TQZ8|||http://purl.uniprot.org/uniprot/Q3UGD6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Acts as a receptor for the ecotropic murine retroviral leukemia virus.|||Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.|||Cell membrane|||High-affinity, low capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues.|||Highest levels found in the testis and bone marrow. Not found in the liver.|||Interacts with TM4SF5; the interaction is negatively regulated by arginine (By similarity). Forms tissue-specific complexes with ASL, ASS1 and nitric oxide synthase NOS1 or NOS3; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway (PubMed:22081021).|||Membrane http://togogenome.org/gene/10090:Hlcs ^@ http://purl.uniprot.org/uniprot/Q3TZ03|||http://purl.uniprot.org/uniprot/Q920N2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the biotin--protein ligase family.|||Biotin--protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase.|||Cytoplasm|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Nrf1 ^@ http://purl.uniprot.org/uniprot/E9Q7X0|||http://purl.uniprot.org/uniprot/G3XA39|||http://purl.uniprot.org/uniprot/Q3UXF4|||http://purl.uniprot.org/uniprot/Q3UYQ3|||http://purl.uniprot.org/uniprot/Q8C4C0|||http://purl.uniprot.org/uniprot/Q8CAV3|||http://purl.uniprot.org/uniprot/Q99K73|||http://purl.uniprot.org/uniprot/Q9WU00 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NRF1/Ewg family.|||Homodimer. Binds DNA as a dimer. Interacts with PPRC1 (By similarity).|||Nucleus|||Phosphorylation enhances DNA binding.|||Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication (By similarity).|||Widely expressed in embryonic, fetal, and adult tissues. http://togogenome.org/gene/10090:Brd9 ^@ http://purl.uniprot.org/uniprot/Q3UQU0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds acetylated histones H3 and H4. Binds butyrylated histone H4 (By similarity). Component of the multiprotein chromatin-remodeling subcomplex SWI/SNF called GBAF, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, the core BAF subunits, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). Interacts (via N-terminal bromodomain) with acteylated RAD54. Interacts (via C-terminus) with RAD51 (By similarity).|||Nucleus|||Plays a role in chromatin remodeling and regulation of transcription. Acts as a chromatin reader that recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Orchestrates also the RAD51-RAD54 complex formation and thereby plays a role in homologous recombination (HR).|||The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions. Also recognizes and binds histones that are butyrylated. http://togogenome.org/gene/10090:Klrb1 ^@ http://purl.uniprot.org/uniprot/Q0ZUP1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fundc2 ^@ http://purl.uniprot.org/uniprot/Q9D6K8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FUN14 family.|||Binds directly and specifically 1,2-Diacyl-sn-glycero-3-phospho-(1'-myo-inositol-3',4',5'-bisphosphate) (PIP3) leading to the recruitment of PIP3 to mitochondria and may play a role in the regulation of the platelet activation via AKT/GSK3B/cGMP signaling pathways (PubMed:30576423, PubMed:29786068). May act as transcription factor that regulates SREBP1 (isoform SREBP-1C) expression in order to modulate triglyceride (TG) homeostasis in hepatocytes (By similarity).|||Highly expressed in platelet (at protein level) (PubMed:29786068, PubMed:30576423). Expressed in liver, brain, heart and muscle (PubMed:29786068).|||Mitochondrion outer membrane|||Nucleus http://togogenome.org/gene/10090:Smc4 ^@ http://purl.uniprot.org/uniprot/Q8CG47 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMC family. SMC4 subfamily.|||Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases (By similarity).|||Chromosome|||Cytoplasm|||Forms a heterodimer with SMC2. Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: BRRN1/CAPH, CNAP1/CAPD2 and CAPG (By similarity).|||Nucleus|||The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC2, forming a V-shaped heterodimer. http://togogenome.org/gene/10090:Exosc9 ^@ http://purl.uniprot.org/uniprot/Q9JHI7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase PH family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts (via C-terminus region) with SETX (via N-terminus domain); the interaction enhances SETX sumoylation (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC9 binds to ARE-containing RNAs (By similarity).|||Nucleus|||The six exosome core subunits containing a RNase PH-domain are not phosphorolytically active.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Slc41a3 ^@ http://purl.uniprot.org/uniprot/G3X937|||http://purl.uniprot.org/uniprot/Q921R8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a magnesium transporter.|||Belongs to the SLC41A transporter family.|||Membrane|||Mitochondrion inner membrane|||Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the mitochondrial inner membrane. http://togogenome.org/gene/10090:Nrip2 ^@ http://purl.uniprot.org/uniprot/Q9JHR9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulates transcriptional activation by nuclear receptors, such as NR1F2.|||Expression is restricted to the central nervous system (neurons in the dentate gyrus of the hippocampus, the amygdala, thalamic and hypothalamic regions).|||Interacts with NR1F2, RARA and THRB in a ligand-dependent manner.|||Nucleus http://togogenome.org/gene/10090:Spef2 ^@ http://purl.uniprot.org/uniprot/Q8C9J3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Golgi apparatus|||Highly expressed in testis, where it primarily localizes to late spermatocytes, round spermatids and elongating spermatids (at protein level) (PubMed:19889948, PubMed:29339787). Found in Sertoli cells of the testis (at protein level) (PubMed:19889948). Expressed at lower levels in epididymis (at protein level) (PubMed:19889948, PubMed:29339787). Detected in lung, brain, liver and kidney (PubMed:19889948, PubMed:29339787). Also detected in bone, cartilage, trachea, pituitary gland and eye (PubMed:29339787). Expressed in osteoblasts and chondrocytes (PubMed:29339787).|||Interacts (via C-terminus) with IFT20 (PubMed:19889948). Interacts with DYNC1I2 (PubMed:28619825).|||Lethality occurs at approximately 3 weeks of age, accompanied by severe hydrocephaly. Weight at birth is similar to wild type but subsequently there is significant growth retardation. Bone mineralization is reduced in the vertebral column and hindlimbs, associated with decreased bone strength. Bone length and skull thickness is also slightly reduced. Trabecular bone density is reduced, along with reduced trabecular number and increased open porosity. Expression of the osteoblast marker genes RUNX2, BGLAP/OCN and COL1A1/COL1 is reduced in bone tissue. Expression of SP7/OSX and ALPL is also reduced in cultured calvarial osteoblasts. Osteoclast differentiation does not appear to be affected. No obvious effects on cilia length or axonemal structure.|||Required for correct axoneme development in spermatozoa (PubMed:21715716, PubMed:28619825). Important for normal development of the manchette and sperm head morphology (PubMed:28619825). Essential for male fertility (PubMed:21715716, PubMed:28619825). Plays a role in localization of the intraflagellar transport protein IFT20 to the manchette, suggesting function as an adapter for dynein-mediated protein transport during spermatogenesis. Also plays a role in bone growth where it seems to be required for normal osteoblast differentiation (PubMed:28619825).|||Shows increasing expression levels in testis during postnatal stages, reaching highest levels by postnatal day 50. In testis, first detected in pachytene spermatocytes (stage VII), reaching peak expression in meitotically dividing spermatocytes (stage XII).|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Rps14 ^@ http://purl.uniprot.org/uniprot/P62264 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS11 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Dnmt1 ^@ http://purl.uniprot.org/uniprot/J3QNW0|||http://purl.uniprot.org/uniprot/P13864|||http://purl.uniprot.org/uniprot/Q3UHZ3|||http://purl.uniprot.org/uniprot/Q7TSJ0 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G(2)/M transition. Deacetylation of Lys-1352 and Lys-1418 by SIRT1 increases methyltransferase activity.|||Allosterically regulated. The binding of 5-methylcytosine-containing DNA to the N-terminal parts of DNMT1 causes an allosteric activation of the catalytic domain by a direct interaction of its Zn-binding domain with the catalytic domain.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.|||Cytoplasm|||Homodimer (By similarity). Forms a stable complex with E2F1, BB1 and HDAC1 (By similarity). Forms a complex with DMAP1 and HDAC2, with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (By similarity). Interacts with UHRF1; promoting its recruitment to hemimethylated DNA (PubMed:21268065). Interacts with USP7, promoting its deubiquitination (PubMed:21268065). Interacts with BAZ2A/TIP5 (PubMed:16085498). Interacts with PCNA (By similarity). Interacts with MBD2 and MBD3 (By similarity). Interacts with DNMT3A and DNMT3B (By similarity). Interacts with UBC9 (By similarity). Interacts with HDAC1 (PubMed:10615135). Interacts with CSNK1D (PubMed:20192920). Interacts with SIRT7 (PubMed:28842251). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity). Interacts with L3MBTL3 and DCAF5; the interaction requires DNMT1 methylation at Lys-139 and is necessary to target DNMT1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex and proteasomal degradation (By similarity). Interacts with PHF20L1; the interaction requires DNMT1 methylation at Lys-139 and protects DNMT1 from ubiquitination and proteasomal degradation (By similarity).|||In germ cells, it is present at high levels in spermatogonia and spermatocytes until the pachytene stage, where it falls to undetectable levels. The transient drop at the pachytene stage coincides with the disappearance of the 5.2 kb mRNA and the accumulation of a larger 6.0 kb mRNA. Oocytes accumulate very large amounts of Dnmt1 protein during the growth phase.|||Isoform 1 is expressed in embryonic stem cells and in somatic tissues. Isoform 2 is expressed in oocytes, preimplantation embryos, testis and in skeletal muscle during myogenesis.|||Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (By similarity). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (By similarity). Promotes tumor growth (By similarity).|||Methylation at Lys-139 by SETD7 is necessary for the regulation of DNMT1 proteasomal degradation.|||Nucleus|||Phosphorylation at Ser-146 by CK1 reduces DNA-binding activity.|||Phosphorylation of Ser-152 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-140 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability.|||Sumoylated; sumoylation increases activity.|||The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation.|||The N-terminal part is required for homodimerization and acts as a regulatory domain.|||There are three 5' exons, one specific to the oocyte (1c), one specific to the pachytene spermatocyte and also found in skeletal muscle (1b) and one found in somatic cells (1a). Three different mRNAs can be produced which give rise to two different translation products: isoform 1 (mRNAs-1a) and isoform 2 (mRNA-1b or -1c). Association of DNMT1 with the replication machinery is not strictly required for maintaining global methylation but still enhances methylation efficiency by 2-fold. Pre-existing cytosine methylation at CpG and non-CpG sites enhances methylation activity.|||Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome. http://togogenome.org/gene/10090:Abcf1 ^@ http://purl.uniprot.org/uniprot/Q6P542 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.|||Cytoplasm|||Interacts (via N-terminus) with EIF2S1; the interaction is independent of its phosphorylated status. Associates (via both ABC transporter domains) with the ribosomes (By similarity).|||Nucleus envelope|||Phosphorylated at phosphoserine and phosphothreonine. Phosphorylation on Ser-107 and Ser-138 by CK2; inhibits association of EIF2 with ribosomes (By similarity).|||Required for efficient Cap- and IRES-mediated mRNA translation initiation. Not involved in the ribosome biogenesis (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Gabra3 ^@ http://purl.uniprot.org/uniprot/P26049|||http://purl.uniprot.org/uniprot/Q8CAB3 ^@ Function|||RNA Editing|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA3 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Binds UBQLN1 (PubMed:11528422). Interacts with GPHN (By similarity).|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane|||The extent of editing is low at birth but increases with age, reaching close to 100% in the adult brain. http://togogenome.org/gene/10090:Gm13271 ^@ http://purl.uniprot.org/uniprot/B1AYH9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Klhl24 ^@ http://purl.uniprot.org/uniprot/Q8BRG6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated. Autoubiquitination leads to proteasomal degradation and is necessary to control KLHL24 levels.|||Controls KRT14 levels during keratinocytes differentiation (PubMed:27798626). As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 (By similarity). Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity). Has a crucial role in cardiac development and function (By similarity).|||Cytoplasm|||Expressed in the brain.|||Forms homodimers. Interacts with GRIK2 (By similarity). Component of the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24. Interacts with CUL3. Interacts with KRT14 (By similarity).|||Perikaryon|||adherens junction|||axon|||desmosome http://togogenome.org/gene/10090:Btf3l4 ^@ http://purl.uniprot.org/uniprot/A2A7Z4|||http://purl.uniprot.org/uniprot/Q9CQH7 ^@ Similarity ^@ Belongs to the NAC-beta family. http://togogenome.org/gene/10090:Tnfsf11 ^@ http://purl.uniprot.org/uniprot/O35235 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor (PubMed:22437732). Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (By similarity). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts (PubMed:18586671, PubMed:24039232, PubMed:27336669). During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (PubMed:23395171, PubMed:26644563).|||Cytoplasm|||Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.|||Highly expressed in thymus and lymph nodes, but not in non-lymphoid tissues and is abundantly expressed in T-cells but not in B-cells. A high level expression is also seen in the trabecular bone and lung.|||Homotrimer (PubMed:11581298, PubMed:11733492, PubMed:20483727). Interacts with TNFRSF11A and TNFRSF11B (PubMed:20483727, PubMed:23039992). Interacts with FBN1 (via N-terminal domain) in a Ca(+2)-dependent manner (PubMed:24039232). Interacts with TNFAIP6 (via both Link and CUB domains).|||N-glycosylated.|||Secreted|||The soluble form of isoform 1 derives from the membrane form by proteolytic processing. The cleavage may be catalyzed by ADAM17. A further shorter soluble form was observed. http://togogenome.org/gene/10090:Or7e177 ^@ http://purl.uniprot.org/uniprot/Q8VFJ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ap1s3 ^@ http://purl.uniprot.org/uniprot/Q7TN05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).|||Belongs to the adaptor complexes small subunit family.|||Cytoplasmic vesicle membrane|||Golgi apparatus|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules (By similarity). Involved in TLR3 trafficking (By similarity).|||clathrin-coated pit http://togogenome.org/gene/10090:Capn12 ^@ http://purl.uniprot.org/uniprot/E9QL26 ^@ Similarity ^@ Belongs to the peptidase C2 family. http://togogenome.org/gene/10090:Gm20920 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Mab21l3 ^@ http://purl.uniprot.org/uniprot/Q8CI17 ^@ Caution|||Similarity ^@ Belongs to the mab-21 family.|||It is uncertain whether Met-1 or Met-68 is the initiator. http://togogenome.org/gene/10090:Phf8 ^@ http://purl.uniprot.org/uniprot/Q80TJ7 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.|||Binds 1 Fe(2+) ion per subunit.|||Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements.|||Interacts with POLR1B, UBTF, SETD1A, HCFC1, E2F1 and ZNF711 (By similarity). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity).|||Nucleus|||Phosphorylation at Ser-33 and Ser-84 are required for dissociation from chromatin and accumulation of H4K20Me1 levels during prophase.|||The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2 (By similarity).|||The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3 (By similarity).|||nucleolus http://togogenome.org/gene/10090:Scamp4 ^@ http://purl.uniprot.org/uniprot/Q3TGX0|||http://purl.uniprot.org/uniprot/Q9JKV5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SCAMP family.|||Membrane|||Probably involved in membrane protein trafficking. http://togogenome.org/gene/10090:Elovl3 ^@ http://purl.uniprot.org/uniprot/O35949 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ELO family. ELOVL3 subfamily.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward saturated and unsaturated acyl-CoA substrates with higher activity toward C18 acyl-CoAs, especially C18:0 acyl-CoAs. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Participates in the formation of certain VLCFA and triglycerides in certain cells of the hair follicles and the sebaceous glands, required for skin barrier function. Critical enzyme for lipid accumulation and metabolic activity in brown adipocytes during the early phase of the tissue recruitment. Plays a role in lipid storage and in resistance to diet-induced obesity.|||Endoplasmic reticulum membrane|||Expressed in brown adipose tissue and liver. In the skin, strong expressed in the cells of the inner layer of the outer root sheath of the hair follicles and in the sebocytes of the sebaceous glands. Hardly detectable in the epidermis and not at all in fibroblasts.|||Mutant mice grow normally and are fertile. They display a sparse hair coat, a hyperplastic pilosebaceous system and their hair lipid content is disturbed with exceptionally high levels of eicosenoic acid (20:1). In the triglyceride fraction, fatty acids longer than 20 carbon atoms are almost undetectable. As a result, mice exhibited a severe defect in water repulsion and increased trans-epidermal water loss. When exposed to cold stress, mutants exhibit a significantly reduced VLCFA elongation activity in brown adipose tissue, but only during the initial phase. Cold-acclimated mutants are equally efficient as normal mice at elongating fatty acids. Mutant mice are lean and resistant to diet-induced weight gain, they show normal food intake but increased metabolic rate, and show reduced hepatic lipogenesis and triglycerides synthesis.|||N-Glycosylated.|||Strongly up-regulated in brown adipose tissue in conditions of brown fat recruitment, such as cold stress, perinatal development and after diet-induced thermogenesis. A synergistic action of both catecholamines and glucocorticoids is required for the induction. http://togogenome.org/gene/10090:H2-DMa ^@ http://purl.uniprot.org/uniprot/Q31621 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Sap30l ^@ http://purl.uniprot.org/uniprot/Q5SQF8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SAP30 family.|||Functions as transcription repressor, probably via its interaction with histone deacetylase complexes. Involved in the functional recruitment of the class 1 Sin3-histone deacetylase complex (HDAC) to the nucleolus. Binds DNA, apparently without sequence-specificity, and bends bound double-stranded DNA. Binds phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate) via the same basic sequence motif that mediates DNA binding and nuclear import.|||Interacts with components of the histone deacetylase complex SIN3A, HDAC1 and HDAC2. Binds histones and nucleosomes. Interacts with FEZ1.|||The zinc-finger domain mediates direct interaction with DNA and phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate). In vitro oxydation causes reversible disulfide bond formation between Cys residues in the zinc-finger domain and reversible loss of zinc ion binding.|||nucleolus http://togogenome.org/gene/10090:Lyst ^@ http://purl.uniprot.org/uniprot/P97412 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes (By similarity). Might regulate trafficking of effectors involved in exocytosis (By similarity). In cytotoxic T-cells and natural killer (NK) cells, has role in the regulation of size, number and exocytosis of lytic granules (By similarity). In macrophages and dendritic cells, regulates phagosome maturation by controlling the conversion of early phagosomal compartments into late phagosomes (PubMed:27881733). In macrophages and dendritic cells, specifically involved in TLR3- and TLR4-induced production of pro-inflammatory cytokines by regulating the endosomal TLR3- TICAM1/TRIF and TLR4- TICAM1/TRIF signaling pathways (PubMed:27881733).|||Cytoplasm|||Defects in Lyst are the cause of beige (bg), an autosomal recessive disorder characterized by hypopigmentation, bleeding, immune cell dysfunction, abnormal intracellular transport to and from the lysosome, and giant inclusion bodies in a variety of cell types.|||Expressed in the heart, lung, liver, spleen, brain and in different immune cell types (purified B and T lymphocytes, bone marrow-derived macrophages and dendritic cells).|||Interacts with CENPJ, LIP8 and ZNF521. http://togogenome.org/gene/10090:Ifi208 ^@ http://purl.uniprot.org/uniprot/Q3V3Q4 ^@ Similarity ^@ Belongs to the HIN-200 family. http://togogenome.org/gene/10090:Pnoc ^@ http://purl.uniprot.org/uniprot/B7ZMX9|||http://purl.uniprot.org/uniprot/Q543U6|||http://purl.uniprot.org/uniprot/Q64387 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the opioid neuropeptide precursor family.|||Blocks nociceptin action in pain transmission by inhibiting nociceptin-induced hyperalgesia and allodynia.|||Brain and spinal cord. Low levels in kidney and spleen.|||Has potent analgesic activity.|||In embryonic brain, first detected at day 14 and in postnatal brain, levels increase in day 1 and day 18. Levels decrease significantly in adults.|||Ligand of the opioid receptor-like receptor OPRL1. It may act as a transmitter in the brain by modulating nociceptive and locomotor behavior. May be involved in neuronal differentiation and development. When administered intracerebroventricularly, nociceptin induces hyperalgesia and decreases locomotor activity.|||Secreted|||Specific enzymatic cleavages at paired basic residues probably yield other active peptides besides nociceptin.|||The N-terminal domain contains 6 conserved cysteines thought to be involved in disulfide bonding and/or processing. http://togogenome.org/gene/10090:C1qtnf1 ^@ http://purl.uniprot.org/uniprot/Q9QXP7 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Mmp8 ^@ http://purl.uniprot.org/uniprot/O70138 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 3 Ca(2+) ions per subunit.|||Can degrade fibrillar type I, II, and III collagens. May play a role in the degradation of collagen fibers during uterine involution.|||Cannot be activated without removal of the activation peptide. Activated by matrilysin.|||Cytoplasmic granule|||Expressed in late embryogenesis and in the involuting postpartum uterus.|||Neutrophils. Expressed in uterus. Low levels in kidney and muscle.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix http://togogenome.org/gene/10090:Gar1 ^@ http://purl.uniprot.org/uniprot/Q9CY66 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GAR1 family.|||Cajal body|||Interaction with SMN1 requires at least one of the RGG-box regions.|||Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. The complex also interacts with TERC, which contains a 3'-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1.|||Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (By similarity).|||nucleolus http://togogenome.org/gene/10090:Mia ^@ http://purl.uniprot.org/uniprot/Q61865 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All malignant melanoma cell lines tested and infrequently in glioma cell lines.|||Belongs to the MIA/OTOR family.|||Elicits growth inhibition on melanoma cells in vitro as well as some other neuroectodermal tumors, including gliomas.|||Interacts with FASLG.|||May possess two intramolecular disulfide bonds.|||Secreted http://togogenome.org/gene/10090:Pkdrej ^@ http://purl.uniprot.org/uniprot/F8VQF3 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the polycystin family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Rmnd5b ^@ http://purl.uniprot.org/uniprot/Q91YQ7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. Catalytic activity of the complex is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1.|||Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles.|||cytosol http://togogenome.org/gene/10090:Tfam ^@ http://purl.uniprot.org/uniprot/P40630 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA via its HMG boxes. When bound to the mitochondrial light strand promoter, bends DNA into a U-turn shape, each HMG box bending the DNA by 90 degrees (By similarity).|||Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (By similarity). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (By similarity). In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (By similarity). Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase (By similarity). Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites (By similarity). Is able to unwind DNA (By similarity). Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes (By similarity). Required for maintenance of normal levels of mitochondrial DNA (PubMed:9500544). May play a role in organizing and compacting mitochondrial DNA (PubMed:17581862).|||Embryonic lethal, due to absence of mitochondrial DNA. Mutant embryos die before 10.5 dpc.|||May also function as a transcriptional activator or may have a structural role in the compaction of nuclear DNA during spermatogenesis.|||Mitochondrion|||Monomer; binds DNA as a monomer. Homodimer. Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT. In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand. Upon metabolic stress, forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT. Interacts with TFB1M and TFB2M. Interacts with CLPX; this enhances DNA-binding.|||Nucleus|||Phosphorylation by PKA within the HMG box 1 impairs DNA binding and promotes degradation by the AAA+ Lon protease.|||The mitochondrial isoform is widely expressed while the nuclear isoform is testis-specific.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Pex11a ^@ http://purl.uniprot.org/uniprot/Q9Z211 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxin-11 family.|||By ciprofibrate.|||Homodimer. Heterodimer with PEX11G. Probably interacts with COPB2 and COPA. Interacts with PEX19. Interacts with FIS1.|||May be involved in peroxisomal proliferation and may regulate peroxisomes division. May mediate binding of coatomer proteins to the peroxisomal membrane (By similarity). Promotes membrane protrusion and elongation on the peroxisomal surface.|||Mice have no detectable defect in constitutive peroxisome division and display a normal peroxisome proliferation response when exposed to PPARalpha-activating drugs. However, they are defective in peroxisome proliferation induced by 4-phenylbutyrate (4-PBA).|||Peroxisome membrane|||Strongly expressed in liver and at lower levels in heart, brain, kidney and testis. http://togogenome.org/gene/10090:Srrm1 ^@ http://purl.uniprot.org/uniprot/Q52KI8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Citrullinated by PADI4.|||Identified in the spliceosome C complex. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRP70, SNRPA1, SRRM1 and SRRM2. Component of the minor spliceosome, which splices U12-type introns (By similarity). Found in a pre-mRNA exonic splicing enhancer (ESE) complex with SNRP70, SNRPA1, SRRM1 and TRA2B/SFRS10. Found in a mRNA splicing-dependent exon junction complex (EJC) with DEK, PRPF8, NCBP1, RBM8A, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with DDX39B, CPSF1, RBM8A, RNPS1, and ALYREF/THOC4. Seems to be a compound of RNA export complexes that are released from speckles in a ATP-dependent manner.|||Nucleus matrix|||Nucleus speckle|||Part of pre- and post-splicing multiprotein mRNP complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). Involved in numerous pre-mRNA processing events. Promotes constitutive and exonic splicing enhancer (ESE)-dependent splicing activation by bridging together sequence-specific (SR family proteins, SFRS4, SFRS5 and TRA2B/SFRS10) and basal snRNP (SNRP70 and SNRPA1) factors of the spliceosome. Stimulates mRNA 3'-end cleavage independently of the formation of an exon junction complex. Binds both pre-mRNA and spliced mRNA 20-25 nt upstream of exon-exon junctions. Binds RNA and DNA with low sequence specificity and has similar preference for either double- or single-stranded nucleic acid substrates.|||Phosphorylated on multiple serine and threonine residues by DYRK3 during the G2-to-M transition, after the nuclear-envelope breakdown. Phosphorylation by DYRK3 promotes disassembly of nuclear speckles. http://togogenome.org/gene/10090:Zfyve9 ^@ http://purl.uniprot.org/uniprot/A2A8R0|||http://purl.uniprot.org/uniprot/A8Y5G5 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Early endosome membrane http://togogenome.org/gene/10090:Sox8 ^@ http://purl.uniprot.org/uniprot/Q04886 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Brain, gut, limb, and testes. Slightly in liver, ovaries, spinal cord, lung and heart.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.|||Transcription factor that may play a role in central nervous system, limb and facial development. May be involved in male sex determination. Binds the consensus motif 5'-[AT][AT]CAA[AT]G-3'. http://togogenome.org/gene/10090:Dmbx1 ^@ http://purl.uniprot.org/uniprot/Q91ZK4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||Detected in embryo from 10.5 to 13.5 dpc. Strongly expressed from 9.5 to 11.5 dpc in the diencephalon, mesencephalon, metencephalon, myeloencephalon, and the developing eye.|||Expressed in adult brain, stomach, and testis. Expressed in the developing diencephalon, midbrain and hindbrain. During limb development, expressed in a temporal pattern with expression being first restricted to the forelimbs and then subsequently to the hindlimbs.|||Functions as a transcriptional repressor. May repress OTX2-mediated transactivation by forming a heterodimer with OTX2 on the P3C (5'-TAATCCGATTA-3') sequence. Required for brain development, neonatal survival, postnatal growth, and nursing ability.|||Homodimer or heterodimer. Forms heterodimers with OTX2.|||Nucleus http://togogenome.org/gene/10090:Ccdc9 ^@ http://purl.uniprot.org/uniprot/Q8VC31 ^@ Function|||Subunit ^@ Probable component of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation.|||Probable component of the exon junction complex (EJC); the association is RNA-dependent. http://togogenome.org/gene/10090:Becn1 ^@ http://purl.uniprot.org/uniprot/O88597 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with murine gammaherpesvirus 68 M11; the viral protein binds BECN1 with higher affinity than cellular BCL2.|||A homodimeric form is proposed to exist; this metastable form readily transits to ATG14- or UVRAG-containing complexes with BECN1:UVRAG being more stable than BECN1:ATG14 (By similarity). Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex whose core is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1, and associates with additional regulatory/auxilliary subunits to form alternative complex forms. Accepted alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are PI3K complex I (PI3KC3-C1) containing ATG14, and PI3K complex II (PI3KC3-C2) containing UVRAG (PubMed:19270693, PubMed:23332761). PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (By similarity). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits, such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:19270693). PI3KC3-C1 probably associates with PIK3CB (PubMed:21059846). Interacts with AMBRA1, GOPC, GRID2 and PIK3CB (PubMed:12372286, PubMed:17589504). Forms a complex with PPP2CA and AMBRA1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (By similarity). Interacts with BCL2 and BCL2L1 isoform Bcl-X(L); the interaction inhibits BECN1 function in promoting autophagy by interfering with the formation of the PI3K complex (By similarity). Interacts with cytosolic HMGB1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with USP10, USP13, VMP1, DAPK1 (By similarity). Interacts with the poly-Gln domain of ATXN3; the interaction causes deubiquitination at Lys-400 and stabilizes BECN1 (PubMed:28445460). Interacts with SLAMF1 (PubMed:22493499). Interacts with TRIM5; the interaction causes activation of BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (By similarity). Interacts with active ULK1 (phosphorylated on 'Ser-317') and MEFV simultaneously (By similarity). Interacts with TRIM50 (PubMed:29604308). Interacts with TRIM16 (By similarity). Interacts with WDR81 and WDR91; negatively regulates the PI3 kinase/PI3K activity associated with endosomal membranes (By similarity). Interacts with LAPTM4B; competes with EGFR for LAPTM4B binding; regulates EGFR activity (By similarity). Interacts with ATG14; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with WASHC1; preventing interaction with AMBRA1 and the DCX(AMBRA1) complex and subsequent ubiquitination (By similarity). Interacts with TRIM17 (By similarity). Interacts with BCL2L10/BCL-B (via BH1 domain) (By similarity). Interacts with SH3BGRL (By similarity). Interacts with Irgm1; enhancing BECN1-interacting partners and influencing the composition of the BECN1 complex (By similarity).|||Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors (By similarity).|||Belongs to the beclin family.|||Cytoplasm|||Death early in embryogenesis. Embryos show a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal (PubMed:14657337). Accelerated neurodegeneration (conditional knockout in cerebellar Purkinje cells).|||Endoplasmic reticulum membrane|||Endosome|||Endosome membrane|||Expanded poly-Gln tracts inhibit ATXN3-BECN1 interaction, decrease BECN1 levels and impair starvation-induced autophagy (PubMed:28445460).|||Mitochondrion|||Mitochondrion membrane|||Nucleus|||Phosphorylation at Thr-117 by DAPK1 reduces its interaction with BCL2 and BCL2L1 and promotes induction of autophagy (By similarity). In response to autophagic stimuli, phosphorylated at serine residues by AMPK in an ATG14-dependent manner, and this phosphorylation is critical for maximally efficient autophagy.|||Plays a central role in autophagy (PubMed:10604474, PubMed:12372286, PubMed:19270693, PubMed:28445460). Acts as core subunit of different PI3K complex forms that mediate formation of phosphatidylinositol 3-phosphate and are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis (PubMed:19270693, PubMed:25275521). Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (By similarity). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms (PubMed:25275521). Involved in endocytosis including endosome formation in neuronal cells (PubMed:25275521). May play a role in antiviral host defense (By similarity).|||Polyubiquitinated by NEDD4, both with 'Lys-11'- and 'Lys-63'-linkages (By similarity). 'Lys-11'-linked poyubiquitination leads to degradation and is enhanced when the stabilizing interaction partner VPS34 is depleted (By similarity). Deubiquitinated by USP10 and USP13, leading to stabilize the PIK3C3/VPS34-containing complexes (By similarity). Polyubiquitinated at Lys-400 with 'Lys-48'-linkages (PubMed:28445460). 'Lys-48'-linked poyubiquitination of Lys-400 leads to degradation (PubMed:28445460). Deubiquitinated by ATXN3, leading to stabilization (PubMed:28445460). Ubiquitinated at Lys-435 via 'Lys-63'-linkage by the DCX(AMBRA1) complex, thereby increasing the association between BECN1 and PIK3C3 to promote PIK3C3 activity (By similarity). 'Lys-48'-linked ubiquitination by RNF216 leads to proteasomal degradation and autophagy inhibition (By similarity).|||Proteolytically processed by caspases including CASP8 and CASP3; the C-terminal fragments lack autophagy-inducing capacity and are proposed to induce apoptosis. Thus the cleavage is proposed to be an determinant to switch from autophagy to apoptosis pathways affecting cellular homeostasis including viral infections and survival of tumor cells.|||The C-terminal evolutionary conserved domain (ECD) contains poly-Gln-binding domains such as the ATXN3 poly-Gln motif, consistent with structural docking models revealing two highly scored poly-Gln-binding pockets in the ECD. As some binding is observed with BECN1 lacking the ECD, other domains of BECN1 may also interact with ATXN3.|||The coiled coil domain can form antiparallel homodimers and mediates dimerization with the coiled coil domains of ATG14 or UVRAG involved in the formation of PI3K complexes.|||autophagosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gm20836 ^@ http://purl.uniprot.org/uniprot/J3QP49 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Edn3 ^@ http://purl.uniprot.org/uniprot/A2APU5|||http://purl.uniprot.org/uniprot/P48299 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the endothelin/sarafotoxin family.|||Endothelins are endothelium-derived vasoconstrictor peptides.|||Secreted http://togogenome.org/gene/10090:Sgcb ^@ http://purl.uniprot.org/uniprot/P82349 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sarcoglycan beta/delta/gamma/zeta family.|||Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.|||Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans.|||Disulfide bonds are present.|||Most strongly expressed in skeletal and heart muscle. Also detected in proliferating myoblasts.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Bhmt2 ^@ http://purl.uniprot.org/uniprot/Q91WS4 ^@ Cofactor|||Function|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Expressed in fetal heart, lung, liver, kidney and eye.|||Homotetramer.|||Involved in the regulation of homocysteine metabolism. Converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor. http://togogenome.org/gene/10090:Sim2 ^@ http://purl.uniprot.org/uniprot/Q61079 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Heterodimer of SIM2 and ARNT.|||Nucleus|||Transcription factor that may be a master gene of CNS development in cooperation with Arnt. It may have pleiotropic effects in the tissues expressed during development.|||Transcripts were detected in high levels in kidney followed by skeletal muscle and lung. Low levels were found in testis, brain and heart. In early fetal development it is found in CNS, developing kidney, tongue epithelium and cartilage primordia. http://togogenome.org/gene/10090:Wdtc1 ^@ http://purl.uniprot.org/uniprot/Q80ZK9 ^@ Function ^@ May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. http://togogenome.org/gene/10090:Dmac1 ^@ http://purl.uniprot.org/uniprot/Q9CQ00 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with incompletely assembled mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).|||Mitochondrion inner membrane|||Required for the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Involved in the assembly of the distal region of complex I. http://togogenome.org/gene/10090:Vmn1r79 ^@ http://purl.uniprot.org/uniprot/Q8R285 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Uimc1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J073|||http://purl.uniprot.org/uniprot/A0A0R4J183|||http://purl.uniprot.org/uniprot/Q5U5Q9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RAP80 family.|||Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (By similarity). Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (By similarity). In the BRCA1-A complex, interacts directly with ABRAXAS1 (By similarity). Interacts with ESR1 (By similarity). Interacts with UBE2I (By similarity). Interacts with NR6A1 (PubMed:7760852). Interacts with TSP57 (PubMed:12954732). Interacts with TRAIP (By similarity).|||Nucleus|||Phosphorylated upon DNA damage by ATM or ATR.|||Sumoylated.|||The Abraxas-interacting region (AIR) mediates the interaction with ABRAXAS1.|||The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity.|||Ubiquitin-binding protein. Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19536136). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1 (By similarity). http://togogenome.org/gene/10090:Trip10 ^@ http://purl.uniprot.org/uniprot/Q8CJ53 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FNBP1 family.|||Cell membrane|||Golgi apparatus|||Homodimerizes, the dimers can polymerize end-to-end to form filamentous structures (By similarity). Interacts with AKAP9, ARHGAP17, DAAM1, DIAPH1, DIAPH2, DNM1, FASLG/FASL, GAPVD1, LYN, microtubules, PDE6G, SRC and WAS/WASP. Interacts with the ligand binding domain of the thyroid receptor (TR) in the presence of thyroid hormone. May interact with CTNNB1 and HD/HTT (By similarity). Interacts specifically with GTP-bound CDC42 and RHOQ. Interacts with DNM2 and WASL.|||Lysosome|||Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Binds to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promotes membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by recruiting WASL/N-WASP which in turn activates the Arp2/3 complex. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Required for the formation of podosomes, actin-rich adhesion structures specific to monocyte-derived cells. May be required for the lysosomal retention of FASLG/FASL (By similarity). Required for translocation of GLUT4 to the plasma membrane in response to insulin signaling.|||The F-BAR domain binds the phospholipid membrane with its concave surface. The end-to-end polymerization of dimers of these domains provides a curved surface that fits best membranes with around 600 A diameter, and may drive tubulation (By similarity).|||Tyrosine phosphorylated. Also phosphorylated by PKA (By similarity).|||cell cortex|||cytoskeleton|||phagocytic cup http://togogenome.org/gene/10090:Gm5134 ^@ http://purl.uniprot.org/uniprot/E9QAB5|||http://purl.uniprot.org/uniprot/Q3V0B7|||http://purl.uniprot.org/uniprot/Q8BIM1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc6a6 ^@ http://purl.uniprot.org/uniprot/O35316|||http://purl.uniprot.org/uniprot/Q3UPI8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A6 subfamily.|||Cell membrane|||Mediates sodium- and chloride-dependent transport of taurine (PubMed:1465453, PubMed:9375654, PubMed:30270321). Can also mediate transport of hypotaurine, beta-alanine and gamma-aminobutyric acid (GABA) (PubMed:1465453, PubMed:9375654, PubMed:30270321).|||Membrane|||Taurine tranport activity is inhibited by phorbol 12-myristate 13-acetate, 3-guanidinopropionic acid, L-2,3- diaminopropionic acid, beta-alanine and hypotaurine.|||Taurine transport activity is down-regulated upon Ser-322 phosphorylation.|||Widely expressed (PubMed:1465453, PubMed:22896705). Highly expressed in the ciliary body of the eye (PubMed:9375654). http://togogenome.org/gene/10090:Serpinb9 ^@ http://purl.uniprot.org/uniprot/O08797 ^@ Similarity ^@ Belongs to the serpin family. Ov-serpin subfamily. http://togogenome.org/gene/10090:Capns2 ^@ http://purl.uniprot.org/uniprot/Q9D7J7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. This small subunit may act as a tissue-specific chaperone of the large subunit, possibly by helping it fold into its correct conformation for activity (By similarity).|||Cell membrane|||Cytoplasm|||Heterodimer of a large (catalytic) and a small (regulatory) subunit. http://togogenome.org/gene/10090:Senp2 ^@ http://purl.uniprot.org/uniprot/Q91ZX6 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates transcription.|||Belongs to the peptidase C48 family.|||Binds to SUMO2 and SUMO3 (By similarity). Interacts with the C-terminal domain of NUP153 via its N-terminus (By similarity). Interacts with MTA1 (By similarity).|||Cytoplasm|||Cytoplasmic vesicle|||Highly expressed in testis. Detected in brain, heart and thymus.|||In 3T3-L1 cells, expression is transiently induced during early adipocyte differentiation (PubMed:20194620).|||Nucleus membrane|||PML body|||Polyubiquitinated; which leads to proteasomal degradation.|||Protease that catalyzes two essential functions in the SUMO pathway (PubMed:11489887, PubMed:20194620). The first is the hydrolysis of an alpha-linked peptide bond at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3 leading to the mature form of the proteins (By similarity). The second is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins, by cleaving an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein (PubMed:11489887, PubMed:20194620, PubMed:27637147). May down-regulate CTNNB1 levels and thereby modulate the Wnt pathway (PubMed:11489887). Deconjugates SUMO2 from MTA1 (By similarity). Plays a dynamic role in adipogenesis by desumoylating and promoting the stabilization of CEBPB (PubMed:20194620). Acts as a regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS and STING1 during the late phase of viral infection (PubMed:27637147).|||The N-terminus is necessary and sufficient for nuclear envelope targeting.|||nuclear pore complex http://togogenome.org/gene/10090:Ripor1 ^@ http://purl.uniprot.org/uniprot/Q68FE6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RIPOR family.|||Cytoplasm|||Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration. Acts as an adapter protein, linking active Rho proteins to STK24 and STK26 kinases, and hence positively regulates Golgi reorientation in polarized cell migration upon Rho activation. Involved in the subcellular relocation of STK26 from the Golgi to cytoplasm punctae in a Rho- and PDCD10-dependent manner upon serum stimulation.|||Expressed in the kidney exclusively by glomerular podocytes.|||Golgi apparatus|||Interacts (via N-terminus) with RHOA (GTP-bound form); this interaction links active RHOA to STK24 and STK26 kinases. Interacts with RHOB. Interacts with RHOC. Interacts (via C-terminus) with PDCD10; this interaction occurs in a Rho-independent manner. Interacts (via C-terminus) with STK24; this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts (via C-terminus) with STK26; this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts (via N-terminus) with 14-3-3 proteins; these interactions occur in a Rho-dependent manner. http://togogenome.org/gene/10090:Tmem125 ^@ http://purl.uniprot.org/uniprot/Q8CHQ6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Hilpda ^@ http://purl.uniprot.org/uniprot/Q9JLS0 ^@ Function|||Induction|||Subcellular Location Annotation ^@ By hypoxia (at protein level).|||Increases intracellular lipid accumulation. Stimulates expression of cytokines including IL6, MIF and VEGFA. Enhances cell growth and proliferation (By similarity).|||Lipid droplet|||Membrane|||Secreted http://togogenome.org/gene/10090:B3gnt3 ^@ http://purl.uniprot.org/uniprot/Q5JCS9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine. Has activity for type 2 oligosaccharides. Also acts as a core1-1,3-N-acetylglucosaminyltransferase (Core1-beta3GlcNAcT) to form the 6-sulfo sialyl Lewis x on extended core1 O-glycans.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Rab7b ^@ http://purl.uniprot.org/uniprot/Q8VEA8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Controls vesicular trafficking from endosomes to the trans-Golgi network (TGN). Acts as a negative regulator of TLR9 signaling and can suppress TLR9-triggered TNFA, IL6, and IFNB production in macrophages by promoting TLR9 lysosomal degradation. Also negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Promotes megakaryocytic differentiation by increasing NF-kappa-B-dependent IL6 production and subsequently enhancing the association of STAT3 with GATA1. Not involved in the regulation of the EGF- and EGFR degradation pathway.|||Golgi apparatus|||Late endosome|||Lysosome|||phagosome|||phagosome membrane|||trans-Golgi network http://togogenome.org/gene/10090:Parp9 ^@ http://purl.uniprot.org/uniprot/Q8CAS9 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by PARP14.|||ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses (PubMed:27796300). Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) (By similarity). In addition, positively regulates DTXL3 protein levels (By similarity). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones (By similarity). During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (By similarity). Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (By similarity). In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ) but the complex function is restrained by PARP9 activity (By similarity). Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (PubMed:28105679). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation (PubMed:27796300). Also suppresses PARP14-mediated STAT6 ADP-ribosylation (By similarity).|||Belongs to the ARTD/PARP family.|||Binding to poly(ADP-ribose) does not affect its activity.|||Developmentally regulated. Expressed prominently in the developing thymus and the gut, and also weakly expressed in specific regions of the developing brain.|||Forms a stable complex with E3 ligase DTX3L; the interaction is required for PARP9 mediated ADP-ribosylation of ubiquitin. Interacts (via PARP catalytic domain) with DTX3L (via N-terminus). Forms a complex with STAT1 and DTX3L independently of IFNB1 or IFNG-mediated STAT1 'Tyr-701' phosphorylation. Forms a complex with STAT1, DTX3L and histone H2B H2BC9/H2BJ; the interaction is likely to induce H2BC9/H2BJ ubiquitination. Interacts (via N-terminus) with STAT1. Interacts with PARP14 in IFNG-stimulated macrophages; the interaction prevents PARP14-mediated STAT1 and STAT6 ADP-riboslylation. Interacts with PARP1 (when poly-ADP-ribosylated).|||Highly expressed in the thymus and intestine (PubMed:18069692). Expressed in macrophages (PubMed:27796300).|||Macro domains 1 and 2 may be involved in the binding to poly(ADP-ribose). Macro domain 2 is required for recruitment to DNA damage sites. Macro domains 1 and 2 are probably dispensable for the interaction with STAT1 and DTX3L and for STAT1 phosphorylation.|||No visible phenotype. Mice are viable, fertile and are born at the expected Mendelian rate with a slight decrease in male frequency. No defect in B-cell development, maturation and maintenance in periphery. Slight decrease in the number of follicular B-cell associated with an increase in the number of marginal zone B-cells.|||Nucleus|||Up-regulated by IFNG in macrophages. Down-regulated by IL4 in macrophages.|||cytosol http://togogenome.org/gene/10090:Or5p70 ^@ http://purl.uniprot.org/uniprot/Q8VF12 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Raf1 ^@ http://purl.uniprot.org/uniprot/Q99N57 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||Cytoplasm|||Methylated at Arg-563 in response to EGF treatment. This modification leads to destabilization of the protein, possibly through proteasomal degradation.|||Mitochondrion|||Monomer (By similarity). Homodimer (By similarity). Heterodimerizes with BRAF and this heterodimer possesses a highly increased kinase activity compared to the respective homodimers or monomers (By similarity). Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins (By similarity). MAPK1/ERK2 activation can induce a negative feedback that promotes the dissociation of the heterodimer (By similarity). Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC) (By similarity). Interacts with LZTR1 (By similarity). Interacts with Ras proteins; the interaction is antagonized by RIN1 (By similarity). Weakly interacts with RIT1 (By similarity). Interacts (via N-terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with BRAF, a ternary complex inhibited by GNAI1 (By similarity). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Interacts with STK3/MST2; the interaction inhibits its pro-apoptotic activity (By similarity). Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr-232') (By similarity). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (By similarity). Interacts with MAP3K5/ASF1 (via N-terminus) and this interaction inhibits the proapoptotic function of MAP3K5/ASK1 (By similarity). Interacts with PAK1 (via kinase domain) (By similarity). The Ser-338 and Ser-339 phosphorylated form (by PAK1) interacts with BCL2 (By similarity). Interacts with PEBP1/RKIP and this interaction is enhanced if RAF1 is phosphorylated on residues Ser-338, Ser-339, Tyr-340 and Tyr-341 (By similarity). Interacts with ADCY2, ADCY5, ADCY6, DGKH, RCAN1/DSCR1, PPP1R12A, PKB/AKT1, SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and PHB/prohibitin (By similarity). The phosphorylated form interacts with PIN1 (PubMed:15664191). Interacts with PPP2CA, PPP2R1B and ROCK2 (PubMed:15753127, PubMed:15664191). In its active form, interacts with PRMT5 (By similarity). Interacts with FAM83B; displaces 14-3-3 proteins from RAF1 and activates RAF1 (By similarity). Interacts with PDE8A; the interaction promotes RAF1 activity (By similarity). Interacts with MFHAS1 (By similarity). Interacts with GLS (By similarity). Interacts with NEK10 and MAP2K1; the interaction is direct with NEK10 and required for ERK1/2-signaling pathway activation in response to UV irradiation (By similarity).|||Nucleus|||Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. Phosphorylation at Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization (By similarity). Phosphorylation at Ser-621 in response to growth factor treatment stabilizes the protein, possibly by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells. Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338. Dephosphorylation at Ser-338 by PPP5C results in a decreased of activity (By similarity).|||Present in all tissues tested: testis, ovary, small intestine, colon, peripheral blood leukocytes, fetal liver, bone marrow, thymus, lymph node and spleen, and the cell lines melanoma G-361, lung carcinoma A-549, colorectal adenocarcinoma SW480, Burkitt's lymphoma Raji and lymphoblastic leukemia MOLT-4. In skeletal muscle, isoform 1 is more abundant than isoform 2.|||Regulation is a highly complex process involving membrane recruitment, protein-protein interactions, dimerization, and phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the membrane, thereby promoting its activation. The inactive conformation of RAF1 is maintained by autoinhibitory interactions occurring between the N-terminal regulatory and the C-terminal catalytic domains and by the binding of a 14-3-3 protein that contacts two phosphorylation sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a fully active kinase. Through a negative feedback mechanism involving MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, desensitized kinase. The signaling-competent conformation of RAF1 is finally re-established by the coordinated action of PIN1, a prolyl isomerase that converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A. Activated by homodimerization and heterodimerization (with BRAF). Also regulated through association with other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting cell membrane localization and phosphorylation of RAF1 at the activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 activation (By similarity).|||Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation (By similarity). Regulates Rho signaling and migration, and is required for normal wound healing. http://togogenome.org/gene/10090:Or5w14 ^@ http://purl.uniprot.org/uniprot/Q7TR40 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myc ^@ http://purl.uniprot.org/uniprot/P01108 ^@ Biotechnology|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alternative translation initiation from an upstream, in-frame non-ATG (CTG) codon or a downstream ATG start site results in the production of 2 isoforms with distinct N-termini, shown in this entry as isoforms 2/3 and isoform 1, respectively.|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX (By similarity). Interacts with TAF1C and SPAG9. Interacts with PARP10. Interacts with KDM5A and KDM5B. Interacts (when phosphorylated at Thr-73 and Ser-77) with FBXW7. Interacts with PIM2 (PubMed:18438430). Interacts with RIOX1. The heterodimer MYC:MAX interacts with ABI1; the interaction may enhance MYC:MAX transcriptional activity (By similarity). Interacts with TRIM6 (PubMed:22328504). Interacts with NPM1; the binary complex is recruited to the promoter of MYC target genes and enhances their transcription (By similarity). Interacts with CIP2A; leading to the stabilization of MYC (By similarity).|||Expressed in the intestinal epithelium (at protein level).|||Expressed in the proliferating cells of the developing CNS and the epidermis. At 10.5, 11.5 and 12.5 dpc, expressed in the spinal cord, within a subset of cells in the proliferative ventricular zone, as well as in the differentiating cells at the ventral portion of the intermediate zone. Also detected in the roof plate and in the neural crest. At 14.5 dpc, found in regions containing differentiating postmitotic neurons. In the developing epidermis at 14.5 dpc, found in the dorsal lateral epidermis. At 17 dpc, expression is confined primarily to the proliferative malphigian layer of the epidermis and to the dermal papilla and primary germ cells in the dermis.|||Expression levels are unaffected by cell density.|||POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.|||Phosphorylated by PRKDC (By similarity). Phosphorylation at Ser-344 by PIM2 leads to the stabilization of MYC (PubMed:18438430). Phosphorylation at Ser-77 by CDK2 prevents Ras-induced senescence. Phosphorylated at Ser-77 by DYRK2; this primes the protein for subsequent phosphorylation by GSK3B at Thr-73. Phosphorylation at Thr-73 and Ser-77 by GSK3 is required for ubiquitination and degradation by the proteasome. Dephosphorylation at Ser-77 by protein phosphatase 2A (PPP2CA) promotes its degradation; interaction with PPP2CA is enhanced by AMBRA1 (By similarity).|||Produced by alternative translation initiation from a CTG codon, which is translated as Met, and alternative splicing.|||Produced by alternative translation initiation from a CTG codon, which is translated as Met.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (PubMed:31005419). Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (By similarity).|||Ubiquitinated by the SCF(FBXW7) complex when phosphorylated at Thr-73 and Ser-77, leading to its degradation by the proteasome. Ubiquitination is counteracted by USP28 in the nucleoplasm and USP36 in the nucleolus, both interacting with of FBXW7, leading to its deubiquitination and preventing degradation. Also polyubiquitinated by the DCX(TRPC4AP) complex (By similarity). Ubiquitinated by TRIM6 in a phosphorylation-independent manner (PubMed:22328504).|||Up-regulated in cultured cells as they reach high density (at protein level).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Or10ag57 ^@ http://purl.uniprot.org/uniprot/Q8VGT9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hpd ^@ http://purl.uniprot.org/uniprot/P49429 ^@ Cofactor|||Disease Annotation|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 4HPPD family.|||Binds 1 Fe cation per subunit.|||Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, one of the steps in tyrosine catabolism.|||Cytoplasm|||Defects in Hpd are the cause of tyrosinemia type III.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer.|||There are two alleles (F1 and F2), F2 has Asp-104 and F1 has Asn-104. Mice are completely tolerant to the self form of the protein, but make a good antibody response to immunization with the non-self form. http://togogenome.org/gene/10090:Adnp ^@ http://purl.uniprot.org/uniprot/Q3UYC8|||http://purl.uniprot.org/uniprot/Q5BL11|||http://purl.uniprot.org/uniprot/Q9Z103 ^@ Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By the neuroprotective peptide VIP.|||Chromosome|||Expressed in the brain, with a higher expression in cerebellum and hippocampus. Weakly expressed in lung, kidney and intestine, and expressed at intermediate level in testis.|||Interacts (via N-terminal region) with beta-catenin/CTNNB1 (via the central armadillo domains); interaction is direct and stabilizes CTNNB1 by modulating its phosphorylation by glycogen synthase kinase-3 beta GSK3B.|||May be involved in transcriptional regulation (PubMed:23071114, PubMed:32533114). May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. Positively modulates WNT-beta-catenin/CTNN1B signaling, acting by regulating phosphorylation of, and thereby stabilizing, CTNNB1 (PubMed:32533114). May be required for neural induction and neuronal differentiation (PubMed:32533114). May be involved in erythroid differentiation (PubMed:23071114).|||Nucleus|||When isolated from the sequence, the neuroprotective peptide provides neuroprotection at subfemtomolar concentrations against toxicity associated with tetrodoxin (electrical blockade), the amyloid-beta peptide (the Alzheimer disease neurotoxin), N-methyl-aspartate (excitotoxicity), and the human immunideficiency virus (HIV) envelope protein. http://togogenome.org/gene/10090:Pcdhgb4 ^@ http://purl.uniprot.org/uniprot/Q91XX6 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Ednra ^@ http://purl.uniprot.org/uniprot/Q61614 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family. Endothelin receptor subfamily. EDNRA sub-subfamily.|||Cell membrane|||Interacts with HDAC7 and KAT5.|||Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3 (By similarity). http://togogenome.org/gene/10090:Ntng2 ^@ http://purl.uniprot.org/uniprot/A2AKW8|||http://purl.uniprot.org/uniprot/Q8R4F1 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expression is detected from embryonic day 9. Strong expression is maintained from embryonic day 14 well into adulthood.|||Expression is restricted primarily to neurons of the CNS, particularly in the cerebral cortex, habenular nucleus and superior colliculus. Low levels in lung, kidney, heart and spleen.|||Interacts with LRRC4.|||Involved in controlling patterning and neuronal circuit formation at the laminar, cellular, subcellular and synaptic levels. Promotes neurite outgrowth of both axons and dendrites.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||The laminin N-terminal domain mediates 1:1 binding to NGL ligand with sub-micromolar affinity. Three NGL-binding loops mediate discrimination for LRRC4/NGL2 among other NGLs by binding specifically to its LRR repeats. This specificity drives the sorting of a mixed population of molecules into discrete cell surface subdomains (By similarity). http://togogenome.org/gene/10090:Rpl35a ^@ http://purl.uniprot.org/uniprot/O55142|||http://purl.uniprot.org/uniprot/Q6ZWX1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL33 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Required for the proliferation and viability of hematopoietic cells (By similarity).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Tor1b ^@ http://purl.uniprot.org/uniprot/Q9ER41 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16 dpc and 18 dpc, widely expressed with higher expression levels in non-neural cells and hippocampus (at protein level).|||Belongs to the ClpA/ClpB family. Torsin subfamily.|||Endoplasmic reticulum lumen|||Highly expressed in liver and muscle; lower expression levels are observed in brain (at protein level).|||Homohexamer. Interacts with TOR1A; the interaction may be specific of neural tissues. Interacts with TOR1AIP1; TOR1AIP1 is required for TOR1B location on the nuclear membrane. Interacts (ATP-bound) with TOR1AIP2; important for endoplasmic reticulum integrity.|||May serve as a molecular chaperone assisting in the proper folding of secreted and/or membrane proteins. Plays a role in non-neural cells nuclear envelope and endoplasmic reticulum integrity. May have a redundant function with TOR1A in non-neural tissues.|||N-glycosylated.|||Nucleus membrane http://togogenome.org/gene/10090:Lins1 ^@ http://purl.uniprot.org/uniprot/Q3U1D0 ^@ Sequence Caution|||Similarity ^@ Belongs to the protein lines family.|||Probable intron retention. http://togogenome.org/gene/10090:Or5al5 ^@ http://purl.uniprot.org/uniprot/A2ARY0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gtf2h1 ^@ http://purl.uniprot.org/uniprot/E9QKD9|||http://purl.uniprot.org/uniprot/G3X8R4|||http://purl.uniprot.org/uniprot/Q7TPY0|||http://purl.uniprot.org/uniprot/Q9DBA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFB1 family.|||Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with PUF60.|||Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.|||Nucleus http://togogenome.org/gene/10090:Prxl2c ^@ http://purl.uniprot.org/uniprot/Q9D1A0 ^@ Function|||Similarity ^@ Belongs to the peroxiredoxin-like PRXL2 family. PRXL2C subfamily.|||May regulate positively ERK1/2 signaling and AKT1 activation leading to HIF1A up-regulation with an increased expression of glycolysis genes and enhanced glycolysis. http://togogenome.org/gene/10090:Nfatc2ip ^@ http://purl.uniprot.org/uniprot/O09130 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highest level detected in spleen, thymus and testis.|||In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression. Down-regulates formation of poly-SUMO chains by UBE2I/UBC9.|||Interacts with NFATC2, TRAF1, TRAF2 and PRMT1. Interacts with UBE2I/UBC9.|||Methylation at the N-terminus by PRMT1 modulates interaction with the NFAT complex and results in augmented cytokine production.|||Mutant mice are born at the expected Mendelian ratio and appear healthy and viable. No alteration in thymic T-cell populations, T-cell proliferation, or peripheral lymphocyte development. Inefficient type-2 antiparasitic immune response to the intestinal nematode Trichinella spiralis due to impaired IL4 and IL13 cytokine production by Th2 cells.|||Nucleus http://togogenome.org/gene/10090:Dab2 ^@ http://purl.uniprot.org/uniprot/P98078 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. Can bind and assemble clathrin, and binds simultaneously to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and cargos containing non-phosphorylated NPXY internalization motifs, such as the LDL receptor, to recruit them to clathrin-coated pits. Can function in clathrin-mediated endocytosis independently of the AP-2 complex. Involved in endocytosis of integrin beta-1; this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. Involved in endocytosis of cystic fibrosis transmembrane conductance regulator/CFTR. Isoform p96 is involved in endocytosis of megalin/LRP2 lipoprotein receptor during embryonal development. Required for recycling of the TGF-beta receptor. Isoform p67 is not involved in LDL receptor endocytosis. Involved in CFTR trafficking to the late endosome. Involved in several receptor-mediated signaling pathways. Involved in TGF-beta receptor signaling and facilitates phosphorylation of the signal transducer SMAD2. Mediates TFG-beta-stimulated JNK activation. May inhibit the canoniocal Wnt/beta-catenin signaling pathway by stabilizing the beta-catenin destruction complex through a competing association with axin preventing its dephosphorylation through protein phosphatase 1 (PP1). Sequesters LRP6 towards clathrin-mediated endocytosis, leading to inhibition of Wnt/beta-catenin signaling. May activate non-canonical Wnt signaling. In cell surface growth factor/Ras signaling pathways proposed to inhibit ERK activation by interrupting the binding of GRB2 to SOS1 and to inhibit SRC by preventing its activating phosphorylation at 'Tyr-419'. Proposed to be involved in modulation of androgen receptor (AR) signaling mediated by SRC activation; seems to compete with AR for interaction with SRC. Plays a role in the CSF-1 signal transduction pathway. Plays a role in cellular differentiation. Involved in cell positioning and formation of visceral endoderm (VE) during embryogenesis and proposed to be required in the VE to respond to Nodal signaling coming from the epiblast. Required for the epithelial to mesenchymal transition, a process necessary for proper embryonic development. May be involved in myeloid cell differentiation and can induce macrophage adhesion and spreading. Isoform p67 may be involved in transcriptional regulation. May act as a tumor suppressor.|||At 6.5 dpc specifically expressed in the cells of the visceral endoderm.|||Cytoplasm|||Embryonic lethal; embryos arrest prior to gastrulation and show lack of endodermal organization, failure to thin the distal tip visceral endoderm (VE), elongate the extra-embryonic portion of the egg cylinder and properly organize the epiblast. Loss of the specific megalin/LRP2 lipoprotein receptor distribution at the brush border at the apical cell edge in presumptive VE cells. Conditionally mutant mice are overtly normal, but have reduced clathrin-coated pits in kidney proximal tubule cells and excrete specific plasma proteins in the urine, consistent with reduced transport by LRP2 in the proximal tubule.|||Interacts (via NPXY motif) with DAB2 (via PID domain). Can interact (via PID domain) with LDLR, APP, APLP1 and APLP2, and weakly with INPP5D (via NPXY motifs); the interaction is impaired by tyrosine phosphorylation of the respective NPXY motifs. Can weakly interact (via PID domain) with LRP1 (via NPXY motif); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif. Interacts with LRP2 (via NPXY motif); the interaction is not affected by tyrosine phosphorylation of the NPXY motif. Interacts with clathrin; in vitro can assemble clathrin triskelia into polyhedral coats. Interacts with AP2A2, ITGB1, ITGB3, ITGB5, PIAS2, DAB2IP, NOSTRIN, FCHO1, DVL3 and EPS15L1. Interacts with SH3KBP1 (via SH3 domains). Interacts with GRB2; competes with SOS1 for binding to GRB2 and the interaction is enhanced by EGF and NT-3 stimulation. Isoform p96 interacts with EPS15 and ITSN1; isoform p67 does not interact with EPS15 and only weakly interacts with ITSN1. Interacts with MAP3K7; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation. Interacts with AXIN1 and PPP1CA; the interactions are mutually exclusive. Interacts with the globular tail of MYO6. Interacts (via DPF motifs) with FCHO2; the interaction is direct and required for DAB2-mediated LDLR endocytosis. Interacts with LRP6; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Associates with the TGF-beta receptor complex (Probable). Interacts with SMAD2 and SMAD3; the interactions are enhanced upon TGF-beta stimulation. Interacts with GRB2; the interaction is enhanced by EGF and NT-3 stimulation. Interacts with SRC; the interaction is enhanced by EGF stimulation.|||Isoform p96 and isoform p67 are expressed in adult kidney and fibroblasts with isoform p96 being the predominant form. Isoform p67 is the predominant isoform expressed in embryonic visceral endoderm.|||Nucleus|||Phosphorylated on serine residues in response to mitogenic growth-factor stimulation. Phosphorylation during mitosis is leading to membrane displacement (By similarity).|||The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of EPS15, EPS15R and ITSN1.|||The PID domain binds to predominantly non-phosphorylated NPXY internalization motifs present in members of the LDLR and APP family; it also mediates simultaneous binding to phosphatidylinositol 4,5-bisphosphate (PubMed:11247302, PubMed:12234931).|||clathrin-coated pit|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Gm20914 ^@ http://purl.uniprot.org/uniprot/J3QME2 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Togaram1 ^@ http://purl.uniprot.org/uniprot/Q6A070 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Crescerin family.|||Interacts with ARMC9. Interacts with CCDC66, CEP104 and CSPP1.|||Involved in ciliogenesis. It is required for appropriate acetylation and polyglutamylation of ciliary microtubules, and regulation of cilium length (By similarity). Interacts with microtubules and promotes microtubule polymerization via its HEAT repeat domains, especially those in TOG region 2 and 4 (PubMed:26378256, PubMed:32747439).|||The TOG regions are composed of HEAT-type repeats that assemble into a solenoid structure. They mediate interaction with microtubules.|||cilium|||cilium axoneme|||cytoskeleton http://togogenome.org/gene/10090:Or5p69 ^@ http://purl.uniprot.org/uniprot/Q8VG07 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:H4c12 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Tmbim6 ^@ http://purl.uniprot.org/uniprot/Q9D2C7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BI1 family.|||Endoplasmic reticulum membrane|||Highly abundant in adult testis.|||Interacts with BCL2 (By similarity). Interacts with BCL2L1 (PubMed:21926971).|||Suppressor of apoptosis (By similarity). Modulates unfolded protein response signaling (By similarity). Modulates ER calcium homeostasis by acting as a calcium-leak channel (By similarity). Negatively regulates autophagy and autophagosome formation, especially during periods of nutrient deprivation, and reduces cell survival during starvation (PubMed:21926971).|||The intra-membrane loop at the C-terminus acts as a calcium pore, mediating calcium leak from the ER into the cytosol. http://togogenome.org/gene/10090:Tmem209 ^@ http://purl.uniprot.org/uniprot/Q8BRG8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Kcne4 ^@ http://purl.uniprot.org/uniprot/Q9WTW3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Associated with KCNQ1/KVLTQ1 inhibits potassium current (By similarity).|||Belongs to the potassium channel KCNE family.|||Interacts with KCNQ1; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity.|||Membrane http://togogenome.org/gene/10090:Il2rg ^@ http://purl.uniprot.org/uniprot/P34902|||http://purl.uniprot.org/uniprot/Q3UPA9|||http://purl.uniprot.org/uniprot/V5SIM2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 5 subfamily.|||Cell membrane|||Cell surface|||Common subunit for the receptors for a variety of interleukins (PubMed:7718508). Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (By similarity).|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||The gamma subunit is common to the IL2, IL4, IL7, IL15, IL21 and probably also the IL13 receptors. Interacts with SHB upon interleukin stimulation (By similarity). Interacts with IL9 (PubMed:7718508). http://togogenome.org/gene/10090:Angptl8 ^@ http://purl.uniprot.org/uniprot/Q8R1L8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ANGPTL8 family.|||Expressed during adipogenesis.|||Expressed in liver and fat. Enriched in white and brown adipose tissues.|||Highly up-regulated following high-fat diet treatment. Down-regulated upon fasting. Strongly induced in the cold environment (4 Degrees Celsius for 4 hours).|||Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels (PubMed:22569073, PubMed:22809513, PubMed:23150577, PubMed:24043787). May be involved in the metabolic transition between fasting and refeeding: required to direct fatty acids to adipose tissue for storage in the fed state (PubMed:24043787). According to a report, may act by promoting ANGPTL3 cleavage (PubMed:23150577). According to another study, not required for cleavage of ANGPTL3 (PubMed:24043787).|||Initially reported to specifically promote pancreatic beta cell proliferation without insulin resistance and to promote beta cell mass expansion, thereby improving glucose tolerance (PubMed:23623304). However, this result could not be confirmed by further studies and the original paper was later retracted (PubMed:28038792). The lack of a role in beta cell proliferation was also confirmed in another study (PubMed:25417115).|||Interacts with ANGPTL3.|||Proteolytically cleaved at the N-terminus.|||Reduced levels of serum triglyceride (PubMed:20562862, PubMed:24043787). Mice gain weight more slowly than wild-type littermates due to a reduction in adipose tissue accretion. Plasma levels of triglycerides are similar to wild-type animals in the fasted state but decreased after refeeding. The lower triglyceride levels are associated with a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity (PubMed:24043787). Glucose and insulin tolerance are not affected and no alterations in glucose homeostasis are observed in mice fed either a chow or high fat diet (PubMed:24043787). Moreover, deletion does not affect the compensatory proliferation of pancreatic beta cells in response to insulin resistance induced by a high-fat diet or treatment with the insulin antagonist S961 (PubMed:25417115).|||Secreted http://togogenome.org/gene/10090:Polr2d ^@ http://purl.uniprot.org/uniprot/Q9D7M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPB4 RNA polymerase subunit family.|||Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB4 is part of a subcomplex with RPB7 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RPB4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).|||Nucleus http://togogenome.org/gene/10090:Grsf1 ^@ http://purl.uniprot.org/uniprot/Q8C5Q4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Mitochondrion matrix|||Monomer. Found in a complex with DDX28, DHX30, FASTKD2 and FASTKD5. Interacts with the mitochondrial RNase P complex subunit TRMT10C/MRPP1. Interacts with the 2 components of the mitochondrial degradosome complex, PNPT1 and SUPV3L1, in an RNA-dependent manner.|||Regulator of post-transcriptional mitochondrial gene expression, required for assembly of the mitochondrial ribosome and for recruitment of mRNA and lncRNA. Binds RNAs containing the 14 base G-rich element. Preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long non-coding RNAs for MT-CYB and MT-ND5, each of which contains multiple consensus binding sequences. Involved in the degradosome-mediated decay of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules. Acts by unwinding G-quadruplex RNA structures in MT-ncRNA, thus facilitating their degradation by the degradosome. G-quadruplexes (G4) are non-canonical 4 stranded structures formed by transcripts from the light strand of mtDNA.|||The RRM domains mediate RNA-binding. http://togogenome.org/gene/10090:Pole3 ^@ http://purl.uniprot.org/uniprot/Q9JKP7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory component of the DNA polymerase epsilon complex (By similarity). Participates in DNA repair and in chromosomal DNA replication (By similarity). Forms a complex with CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1 (By similarity). Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex (By similarity).|||Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interaction with POLE4 is a prerequisite for further binding with POLE and POLE2. Heterodimer with CHRAC1; binds to DNA (By similarity). Component of the CHRAC ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H, BAZ1A/ACF1, CHRAC1 and POLE3; the complex preferentially binds DNA through the CHRAC1-POLE3 heterodimer and possesses ATP-dependent nucleosome-remodeling activity (By similarity). Within the complex, the heterodimer with CHRAC1 interacts with SMARCA5/SNF2H; the interaction is direct and enhances nucleosome sliding activity by the SMARCA5/SNF2H and BAZ1A/ACF1 interaction (By similarity). Within the complex, the heterodimer with CHRAC1 interacts with BAZ1A/ACF1; the interactions are direct (By similarity).|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Hcar2 ^@ http://purl.uniprot.org/uniprot/Q0VBA6|||http://purl.uniprot.org/uniprot/Q9EP66 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis.|||Belongs to the G-protein coupled receptor 1 family.|||By interferon-gamma in macrophages.|||Cell membrane|||Expressed in lungs, spleen, heart, skeletal muscle and adipose tissue.|||Membrane|||Niacin administration has no effect on serum adiponectin levels in contrast to wild-type mice where levels are decreased. http://togogenome.org/gene/10090:Sac3d1 ^@ http://purl.uniprot.org/uniprot/A6H687 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAC3 family.|||Involved in centrosome duplication and mitotic progression.|||May be part of a SEM1-containing complex.|||Present in spleen cells (at protein level).|||centrosome|||spindle http://togogenome.org/gene/10090:Polr2a ^@ http://purl.uniprot.org/uniprot/P08775 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated and dimethylated. EP300 is one of the enzyme able to acetylate 'Lys-7'. Acetylation at 'Lys-7' of non-consensus heptapeptide repeats is associated with 'Ser-2' phosphorylation and active transcription. It may regulate initiation or early elongation steps of transcription specially for inducible genes.|||Belongs to the RNA polymerase beta' chain family.|||Chromosome|||Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits (By similarity). Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin (PubMed:19141475). The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active) (PubMed:22767893). Interacts (via the C-terminal domain (CTD)) with U2AF2; recruits PRPF19 and the Prp19 complex to the pre-mRNA and may couple transcription to pre-mRNA splicing. Interacts (via the C-terminal domain (CTD)) with SMN1/SMN2; recruits SMN1/SMN2 to RNA Pol II elongation complexes. Interacts via the phosphorylated C-terminal domain with WDR82 and with SETD1A and SETD1B only in the presence of WDR82. When phosphorylated at 'Ser-5', interacts with MEN1; the unphosphorylated form, or phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-5', interacts with ZMYND8; the form phosphorylated at 'Ser-2' does not interact. When phosphorylated at 'Ser-2', interacts with SUPT6H (via SH2 domain). Interacts with RECQL5 and TCEA1; binding of RECQL5 prevents TCEA1 binding. The phosphorylated C-terminal domain interacts with FNBP3 and SYNCRIP. Interacts with ATF7IP. Interacts with DDX5 (By similarity). Interacts with WWP2 (PubMed:17526739). Interacts with SETX. Interacts (phosphorylated) with PIH1D1. Interacts (via the C-terminal domain (CTD)) with TDRD3. Interacts with PRMT5. Interacts with XRN2. Interacts with SAFB/SAFB1 (By similarity). Interacts with CCNL1 (Probable). Interacts with CCNL2 (By similarity). Interacts with MYO1C (PubMed:11030652). Interacts with PAF1 (By similarity). Interacts with SFRS19 (By similarity). Interacts (via C-terminus) with CMTR1 (By similarity). Interacts (via C-terminus) with CTDSP1 (By similarity). Interacts (via C-terminus) with SCAF8 (PubMed:8692929). Interacts (via the C-terminal domain (CTD)) with CCNT2. Interacts with FUS (By similarity). Interacts with MCM3AP. Interacts with kinase SRPK2; the interaction occurs during the co-transcriptional formation of inappropriate R-loops (By similarity). Interacts with SETD2 (By similarity). Interacts with UVSSA (By similarity). Interacts with ERCC6 (By similarity). Interacts with the TFIIH complex (By similarity).|||Cytoplasm|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB1 is part of the core element with the central large cleft, the clamp element that moves to open and close the cleft and the jaws that are thought to grab the incoming DNA template. At the start of transcription, a single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol II. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. During transcription elongation, Pol II moves on the template as the transcript elongates (By similarity). Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing (By similarity). Regulation of gene expression levels depends on the balance between methylation and acetylation levels of tha CTD-lysines (PubMed:26687004). Initiation or early elongation steps of transcription of growth-factors-induced immediate early genes are regulated by the acetylation status of the CTD (PubMed:24207025). Methylation and dimethylation have a repressive effect on target genes expression (PubMed:26687004).|||Methylated at Arg-1810 prior to transcription initiation when the CTD is hypophosphorylated, phosphorylation at Ser-1805 and Ser-1808 preventing this methylation. Symmetrically or asymmetrically dimethylated at Arg-1810 by PRMT5 and CARM1 respectively. Symmetric or asymmetric dimethylation modulates interactions with CTD-binding proteins like SMN1/SMN2 and TDRD3. SMN1/SMN2 interacts preferentially with the symmetrically dimethylated form while TDRD3 interacts with the asymmetric form. Through the recruitment of SMN1/SMN2, symmetric dimethylation is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. CTD dimethylation may also facilitate the expression of select RNAs. Among tandem heptapeptide repeats of the C-terminal domain (CTD) some do not match the Y-S-P-T-S-P-S consensus, the seventh serine residue 'Ser-7' being replaced by a lysine. 'Lys-7' in these non-consensus heptapeptide repeats can be alternatively acetylated, methylated, dimethylated and trimethylated. Methylation occurs in the earliest transcription stages and precedes or is concomitant to 'Ser-5' and 'Ser-7' phosphorylation. Dimethylation and trimehtylation at 'Lys-7' of non-consensus heptapeptide repeats are exclusively associated with phosphorylated CTD.|||Nucleus|||The C-terminal domain (CTD) serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing.|||The binding of ribonucleoside triphosphate to the RNA polymerase II transcribing complex probably involves a two-step mechanism. The initial binding seems to occur at the entry (E) site and involves a magnesium ion temporarily coordinated by three conserved aspartate residues of the two largest RNA Pol II subunits. The ribonucleoside triphosphate is transferred by a rotation to the nucleotide addition (A) site for pairing with the template DNA. The catalytic A site involves three conserved aspartate residues of the RNA Pol II largest subunit which permanently coordinate a second magnesium ion.|||The tandem heptapeptide repeats in the C-terminal domain (CTD) can be highly phosphorylated. The phosphorylation activates Pol II. Phosphorylation occurs mainly at residues 'Ser-2' and 'Ser-5' of the heptapeptide repeat and is mediated, at least, by CDK7 and CDK9. CDK7 phosphorylation of POLR2A associated with DNA promotes transcription initiation by triggering dissociation from DNA. Phosphorylation also takes place at 'Ser-7' of the heptapeptide repeat, which is required for efficient transcription of snRNA genes and processing of the transcripts. The phosphorylation state is believed to result from the balanced action of site-specific CTD kinases and phosphatases, and a 'CTD code' that specifies the position of Pol II within the transcription cycle has been proposed. Dephosphorylated by the protein phosphatase CTDSP1. Dephosphorylated at 'Ser-2' following UV irradiation.|||Ubiquitinated by WWP2 leading to proteasomal degradation (PubMed:17526739). Following transcription stress, the elongating form of RNA polymerase II (RNA pol IIo) is ubiquitinated by NEDD4 on Lys-1268 at DNA damage sites without leading to degradation: ubiquitination promotes RNA pol IIo backtracking to allow access by the transcription-coupled nucleotide excision repair (TC-NER) machinery (By similarity). At stalled RNA pol II where TC-NER has failed, RBX1-mediated polybiquitination at Lys-1268 may lead to proteasome-mediated degradation in a UBAP2- and UBAP2L-dependent manner; presumably to halt global transcription and enable 'last resort' DNA repair pathways (By similarity). http://togogenome.org/gene/10090:Dnajc10 ^@ http://purl.uniprot.org/uniprot/Q9DC23 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum disulfide reductase involved both in the correct folding of proteins and degradation of misfolded proteins. Required for efficient folding of proteins in the endoplasmic reticulum by catalyzing the removal of non-native disulfide bonds formed during the folding of proteins, such as LDLR. Also involved in endoplasmic reticulum-associated degradation (ERAD) by reducing incorrect disulfide bonds in misfolded glycoproteins recognized by EDEM1. Interaction with HSPA5 is required its activity, not for the disulfide reductase activity, but to facilitate the release of DNAJC10 from its substrate. Promotes apoptotic signaling pathway in response to endoplasmic reticulum stress.|||Endoplasmic reticulum lumen|||Interacts with HSPA5 (via its J domain). Interacts with EDEM1.|||Mice are viable and healthy but show enhanced endoplasmic reticulum stress response in the salivary gland.|||The thioredoxin-like regions Trxb 1 and 2 lack a redox-active CXXC motif.|||Thioredoxin domains 3 and 4 are the primary reductase domains.|||Ubiquitous. Particularly abundant in secretory tissues. Ubiquitous in fetal tissues and tumor tissues. Higher expression in fetal tissues than in adult tissues. Expressed in testis, pancreas, fetal thymus and fetal kidney. High expression in heart, liver, kidney, and testis. Low expression in spleen and skeletal muscle. http://togogenome.org/gene/10090:Rpl38 ^@ http://purl.uniprot.org/uniprot/Q52KP0|||http://purl.uniprot.org/uniprot/Q9JJI8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL38 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Arhgdig ^@ http://purl.uniprot.org/uniprot/Q3UNB6|||http://purl.uniprot.org/uniprot/Q62160 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Rho GDI family.|||Cytoplasm|||Detected only in brain, lung, kidney and testis.|||Inhibits GDP/GTP exchange reaction of RhoB. Interacts specifically with the GDP- and GTP-bound forms of post-translationally processed Rhob and Rhog proteins, both of which show a growth-regulated expression in mammalian cells. Stimulates the release of the GDP-bound but not the GTP-bound RhoB protein. Also inhibits the GDP/GTP exchange of RhoB but shows less ability to inhibit the dissociation of prebound GTP. http://togogenome.org/gene/10090:Cfap58 ^@ http://purl.uniprot.org/uniprot/B2RW38 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CFAP58 family.|||Has an essential role in the assembly and organization of the sperm flagellar axoneme (PubMed:32791035). Required for the elongation of the primary cilium and sperm flagellar midpiece via modulation of the Notch signaling pathway (PubMed:31904090).|||Interacts with ODFP2.|||Male mice are infertile with severely decreased sperm motility and abnormal sperm flagellar morphology.|||Predominantly expressed in the testis (PubMed:32791035, PubMed:31904090). Also found at lower levels in ciliated cells and tissues such as neural progenitor cells and oviducts (PubMed:31904090).|||centrosome|||cilium|||flagellum http://togogenome.org/gene/10090:Or6c203 ^@ http://purl.uniprot.org/uniprot/Q8VGC5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chrd ^@ http://purl.uniprot.org/uniprot/A6H5Z6|||http://purl.uniprot.org/uniprot/Q9Z0E2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chordin family.|||Cleaved by tolloid proteases; cleavage participates in dorsoventral patterning during early development.|||Detected at high levels in 7 dpc mouse embryos; its level decreases at later developmental stages and in adult tissues.|||Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes.|||Interacts with TWSG1 and/or BMP4.|||Secreted http://togogenome.org/gene/10090:Slc6a2 ^@ http://purl.uniprot.org/uniprot/O55192|||http://purl.uniprot.org/uniprot/Q8R2I2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A2 subfamily.|||Cell membrane|||Interacts with PRKCABP.|||Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:16269905). Can also mediate sodium- and chloride-dependent transport of dopamine (By similarity).|||Membrane|||This protein is the target of psychomotor stimulants such as amphetamines or cocaine. http://togogenome.org/gene/10090:Krt79 ^@ http://purl.uniprot.org/uniprot/Q8VED5 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Phldb2 ^@ http://purl.uniprot.org/uniprot/Q8K1N2 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed at postsynaptic membranes of skeletal neuromuscular junctions (at protein level).|||In synapses, is expressed at embryonic day 15 and colocalizes with acetyl-choline receptor at prenatal day 4. Expression decreases in adult.|||Interacts with FLNC.|||Membrane|||Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane.|||The PH domain mediates the binding to phosphoinositides. http://togogenome.org/gene/10090:Dnase1 ^@ http://purl.uniprot.org/uniprot/P49183|||http://purl.uniprot.org/uniprot/Q14BW6 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DNase I family.|||Divalent metal cations. Prefers Ca(2+) or Mg(2+).|||Highly expressed in the parotid and submandibular gland as well as in the kidney and duodenum (at protein level) (PubMed:15015938). Expressed at intermediate level in the ileum, mesenterial lymph nodes, liver, ventral prostate, epididymis, ovary and stomach (at protein level) (PubMed:15015938). Expressed at low level in the sublingual, preputial, coagulation and pituitary gland (at protein level) (PubMed:15015938). Also present in the lachrymal and thyroid glands, striated muscle, intestine, the urinary bladder and the eye (PubMed:7857306, PubMed:9192086, PubMed:15015938).|||Mice develop symptoms of the autoimmune disease systemic lupus erythematosus, characterized by high titers of anti-nuclear autoantibodies (ANA) directed against nucleosomes and double-stranded DNA, the deposition of immune complexes in glomeruli and full-blown glomerulonephritis (PubMed:10835632). Mice lacking both Dnase1 and Dnase1l3 show vascular occlusions following bacterial infection: defects are caused by the formation of intravascular neutrophil extracellular traps (NETs) clots that obstruct blood vessels and cause organ damage (PubMed:29191910).|||N-glycosylated.|||Nucleus envelope|||Secreted|||Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PubMed:29191910). Expressed by non-hematopoietic tissues and preferentially cleaves protein-free DNA. Among other functions, seems to be involved in cell death by apoptosis. Binds specifically to G-actin and blocks actin polymerization (By similarity). Together with DNASE1L3, plays a key role in degrading neutrophil extracellular traps (NETs) (PubMed:29191910). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:29191910). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (PubMed:29191910).|||Zymogen granule http://togogenome.org/gene/10090:Mettl15 ^@ http://purl.uniprot.org/uniprot/Q9DCL4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methyltransferase superfamily. RsmH family.|||Mitochondrion matrix|||N4-methylcytidine (m4C) methyltransferase responsible for the methylation of position C839 in mitochondrial 12S rRNA. Involved in the stabilization of 12S rRNA folding, therefore facilitating the assembly of the mitochondrial small ribosomal subunits. http://togogenome.org/gene/10090:Tbx4 ^@ http://purl.uniprot.org/uniprot/P70325|||http://purl.uniprot.org/uniprot/Q8BSY3 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation ^@ First expressed at day 7.5, exclusively in the allantois where expression continues through day 8.5. At day 9.5, expression is found in the genital papilla, body wall and limb buds (higher levels in hindlimb). At day 12.5, expressed in the mesenchyme of the mandibular arch, of the lung and of that surrounding the trachea. Also found in the sinus venosus/common atrium of the developing heart.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Transcriptional regulator that has an essential role in the organogenesis of lungs, pelvis, and hindlimbs. http://togogenome.org/gene/10090:Rnpc3 ^@ http://purl.uniprot.org/uniprot/Q3UZ01 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Found in a complex with m(7)G-capped U12 snRNA. Interacts with PDCD7 (By similarity).|||Nucleus|||Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'-stem-loop of m(7)G-capped U12 snRNA (By similarity). http://togogenome.org/gene/10090:Psmb4 ^@ http://purl.uniprot.org/uniprot/P99026 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1B family.|||Cytoplasm|||Detected in liver (at protein level).|||Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Forms a ternary complex with SMAD1 and OAZ1 before PSMB4 is incorporated into the 20S proteasome (By similarity). Interacts with PRPF19 (By similarity).|||Up-regulated in liver tumor tissues (at protein level). http://togogenome.org/gene/10090:Sptssa ^@ http://purl.uniprot.org/uniprot/Q8R207 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPTSS family. SPTSSA subfamily.|||Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides. Interacts with MBOAT7; the interaction plays a role in MBOAT7 localization to mitochondria-associated membranes.|||Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. Within the SPT complex, SPTSSA stimulates the catalytic activity and plays a role in substrate specificity, which depends upon the overall complex composition. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. Independently of its action as a SPT component, may be involved in MBOAT7 localization to mitochondria-associated membranes, a membrane bridge between the endoplasmic reticulum and mitochondria, may hence affect MBOAT7-catalyzed incorporation of arachidonic acid into phosphatidylinositol.|||Endoplasmic reticulum membrane|||It is uncertain whether Met-1 or Met-4 is the initiator. http://togogenome.org/gene/10090:Apoc2l ^@ http://purl.uniprot.org/uniprot/Q05020|||http://purl.uniprot.org/uniprot/Q3UJG0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adult and fetal liver, intestine and peritoneal macrophages.|||Belongs to the apolipoprotein C2 family.|||Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase.|||Secreted http://togogenome.org/gene/10090:Defa33 ^@ http://purl.uniprot.org/uniprot/Q8C1N9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Cyp2j5 ^@ http://purl.uniprot.org/uniprot/O54749|||http://purl.uniprot.org/uniprot/Q3TNC5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Syngap1 ^@ http://purl.uniprot.org/uniprot/F6SEU4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with KLHL17, CAMK2A and CAMK2B. Interacts with MPDZ (By similarity).|||Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. Exhibits dual GTPase-activating specificity for Ras and Rap. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits (By similarity).|||Membrane|||Synapse|||The C2 domain is required for RapGAP activity. http://togogenome.org/gene/10090:Med13 ^@ http://purl.uniprot.org/uniprot/Q5SWW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 13 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gnao1 ^@ http://purl.uniprot.org/uniprot/P18872|||http://purl.uniprot.org/uniprot/Q543S2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||Cell membrane|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Forms a complex with GNB1 and GNG3 (By similarity). Interacts with RGS14. Interacts with RGS19 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Stimulated by RGS14. The G(o) protein function is not clear.|||Histaminylated at Gln-205 residues by TGM2.|||Membrane http://togogenome.org/gene/10090:Tmbim4 ^@ http://purl.uniprot.org/uniprot/Q9DA39 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release (By similarity).|||Belongs to the BI1 family. LFG subfamily.|||Golgi apparatus membrane|||Interacts with ITPR3. http://togogenome.org/gene/10090:Rbm5 ^@ http://purl.uniprot.org/uniprot/Q91YE7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RBM5/RBM10 family.|||Component of the spliceosome A complex (also known as the prespliceosome). Appears to dissociate from the spliceosome upon formation of the spliceosome B complex (also known as the precatalytic spliceosome), in which the heterotrimeric U4/U6.U5 snRNPs are bound. Interacts with U2AF2; this interaction is direct. Also interacts with ACIN1, PRPF8, SFRS3, SNRPB, SNRPN, SNRNP70 and SNRNP200; these interactions may be indirect (By similarity).|||Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate apoptosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes production of a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes production of a catalytically active form of CASP2/Caspase-2 that induces apoptosis (By similarity).|||Nucleus http://togogenome.org/gene/10090:Atp11b ^@ http://purl.uniprot.org/uniprot/Q6DFW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of intracellular membranes. May contribute to the maintenance of membrane lipid asymmetry in endosome compartment.|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP11B and an accessory beta subunit TMEM30A.|||Early endosome|||Endoplasmic reticulum|||Expressed in retina, brain, liver, testes and kidney (at protein level).|||Recycling endosome membrane|||trans-Golgi network http://togogenome.org/gene/10090:Brcc3 ^@ http://purl.uniprot.org/uniprot/P46737 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M67A family. BRCC36 subfamily.|||Binds 1 zinc ion per subunit.|||Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1 and BABAM2. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. In the BRISC complex, interacts directly with ABRAXAS2. Identified in a complex with ABRAXAS2 and NUMA1. The BRISC complex interacts with the CSN complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BABAM2 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. Interacts with BRCA1. Binds polyubiquitin (By similarity). Interacts with PWWP2B (PubMed:34180153). Interacts with HDAC1; this interaction is enhanced in the presence of PWWP2B (PubMed:34180153).|||Cytoplasm|||Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:23246432, PubMed:34180153). Does not have activity toward 'Lys-48'-linked polyubiquitin chains (By similarity). Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs) (By similarity). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs) (By similarity). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (By similarity). Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex (By similarity). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (By similarity). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (By similarity). Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly (PubMed:23246432, PubMed:28943315). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (By similarity). Deubiquitinates HDAC1 and PWWP2B leading to their stabilization (PubMed:34180153).|||Nucleus|||spindle pole http://togogenome.org/gene/10090:Cog7 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Q9|||http://purl.uniprot.org/uniprot/Q3UM29 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG7 family.|||Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.|||Golgi apparatus membrane|||Membrane|||Required for normal Golgi function. http://togogenome.org/gene/10090:Krt7 ^@ http://purl.uniprot.org/uniprot/Q9DCV7 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Arg-15 is dimethylated, probably to asymmetric dimethylarginine.|||Belongs to the intermediate filament family.|||Blocks interferon-dependent interphase and stimulates DNA synthesis in cells.|||Expressed in most simple epithelia tested including liver, lactating mammary gland, lung, kidney, stomach, duodenum, colon, oviduct, uterus, pancreas, epididymis, prostate, preputial gland and mesothelium, and in most stratified epithelia tested including dorsal skin, paw/toe, tail, tongue, cervix, forestomach, and bladder. Also expressed in Henle layer of the inner root sheath of whisker follicle.|||Heterotetramer of two type I and two type II keratins. Interacts with eukaryotic translation initiator factor 3 (eIF3) subunit EIF3S10. Interacts with GPER1 (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Nacc1 ^@ http://purl.uniprot.org/uniprot/Q7TSZ8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Functions as a transcriptional repressor. Seems to function as a transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell proliferation and survival. This may be mediated at least in part through repressing transcriptional activity of GADD45GIP1. Required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines. Involved in the acute behavioral and neurological responses to cocaine and amphetamines.|||Homooligomer; mediated by the BTB domain. Interacts with HDAC3 and HDAC4. Interacts (via BTB domain) with CUL3, PSMD7 and RCOR1 (By similarity).|||Mice are viable with no obvious developmental or physiological impairments. In addition, they do not display alterations in chronic responses to cocaine and amphetamine administration, but do however display significantly diminished acute behavioral and neurochemical responses to these drugs.|||Nucleus|||Ubiquitously expressed with higher expression in the brain, kidney and liver, and at lower levels in heart, lung and testes. http://togogenome.org/gene/10090:Apmap ^@ http://purl.uniprot.org/uniprot/Q9D7N9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the strictosidine synthase family.|||Exhibits strong arylesterase activity with beta-naphthyl acetate and phenyl acetate (By similarity). May play a role in adipocyte differentiation.|||Expressed during adipocyte differentiation. Expression appears 3 days following induction of adipose conversion.|||Glycosylated in vitro.|||Membrane|||Strongly expressed in adipose tissue. Highly expressed in liver, heart, and kidney. Expressed at intermediate level in brain and lung. Weakly expressed in spleen, skeletal muscle and testis. http://togogenome.org/gene/10090:Ahctf1 ^@ http://purl.uniprot.org/uniprot/Q8CJF7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the Nup107-160 subcomplex of the NPC.|||Belongs to the ELYS family.|||Cytoplasm|||Embryonic lethality before 7.5 dpc. Impaired proliferation of the inner cells of the blastocyst due at least in part to increased apoptosis.|||Expressed throughout the embryo at 3.5 dpc and 6.5 dpc. Higher expression is detected at 10.5 dpc nad then progressively decreases. Highly expressed in fetal hematopoietic tissues including liver, spleen and thymus. Expressed in the endothelium lining the dorsal aorta of 11.5 dpc embryos (at protein level).|||Nucleus matrix|||Required for the assembly of a functional nuclear pore complex (NPC) on the surface of chromosomes as nuclei form at the end of mitosis. May initiate NPC assembly by binding to chromatin and recruiting the Nup107-160 subcomplex of the NPC. Also required for the localization of the Nup107-160 subcomplex of the NPC to the kinetochore during mitosis and for the completion of cytokinesis (By similarity). Has also been proposed to function as a transcription factor which may play a specific role in hematopoietic tissues (PubMed:11952839).|||The N-terminus forms a highly conserved seven-bladed beta propeller decorated with long loops and mediates anchorage to the Nup107-160 subcomplex of the nuclear pore, synergistically with the central alpha domain. The disordered C-terminus is responsible for the interactions with chromatin (PubMed:23499022).|||Widely expressed with higher expression in testis, lung and kidney. Expressed in T-cells, B-cells and granulocytes in bone marrow.|||kinetochore|||nuclear pore complex|||nucleoplasm http://togogenome.org/gene/10090:Exoc6b ^@ http://purl.uniprot.org/uniprot/A6H5Z3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the SEC15 family.|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||The exocyst complex is composed of SEC3, SEC5, SEC6, SEC8, SEC10, SEC15, EXO70 and EXO84. http://togogenome.org/gene/10090:Cyp2a22 ^@ http://purl.uniprot.org/uniprot/B2RXZ2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Gm30302 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VN40 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Psmd6 ^@ http://purl.uniprot.org/uniprot/Q99JI4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the proteasome subunit S10 family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD6, a base containing 6 ATPases and few additional components.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. http://togogenome.org/gene/10090:Cwc27 ^@ http://purl.uniprot.org/uniprot/Q3TKY6 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the spliceosome, plays a role in pre-mRNA splicing. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Belongs to the cyclophilin-type PPIase family.|||Despite the fact that it belongs to the cyclophilin-type PPIase family, it has probably no peptidyl-prolyl cis-trans isomerase activity.|||Knockout mice manifest significant embryonic lethality. Growth retardation, lack of neural tube closure, and absence of limb buds are observed at embryonic day 12.5. Surviving mice show growth retardation and retinal dystrophic changes.|||Nucleus|||Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed at least of 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Recruited during early steps of activated spliceosome B maturation, it is probably one of the first proteins released from this complex as he matures to the spliceosome C complex. Component of the minor spliceosome, which splices U12-type introns (By similarity). http://togogenome.org/gene/10090:Rhbg ^@ http://purl.uniprot.org/uniprot/Q8BUX5 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ammonium transporter involved in the maintenance of acid-base homeostasis. Transports ammonium and its related derivative methylammonium across the basolateral plasma membrane of epithelial cells likely contributing to renal transepithelial ammonia transport and ammonia metabolism. May transport either NH4(+) or NH3 ammonia species predominantly mediating an electrogenic NH4(+) transport (PubMed:15353405, PubMed:16131648, PubMed:20592240, PubMed:27681563) (By similarity). May act as a CO2 channel providing for renal acid secretion (By similarity).|||Basolateral cell membrane|||Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.|||Cell membrane|||Detected in embryos at 15 dpc and 17 dpc. Expressed in kidney, skin and liver of 16.5 dpc embryos.|||Expressed in kidney by connecting segments and collecting tubules. Also expressed in liver by perivenous hepatocytes. Expressed in the forestomach and the fundus of the stomach. Expressed in duodenum, jejunum, ileum and colon at the level of villous (at protein level). Specifically expressed in kidney where it is restricted to the epithelial linings of the convoluted tubules and the loop of Henle. Also detected in ovary. Expressed by hepatocytes and dermal hair follicles and papillae.|||Inhibited by amiloride.|||Interacts (via C-terminus) with ANK2 and ANK3; required for targeting to the basolateral membrane.|||N-glycosylated. http://togogenome.org/gene/10090:Ccnd1 ^@ http://purl.uniprot.org/uniprot/P25322|||http://purl.uniprot.org/uniprot/Q790L7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin D subfamily.|||Cytoplasm|||Expressed in the intestinal epithelium.|||Interacts with either CDK4 or CDK6 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Component of the ternary complex CCND1/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity (By similarity). Interacts directly with CDKN1B (PubMed:8534916, PubMed:19767775). Can form similar complexes with either CDKN1A or CDKN2A (PubMed:8534916). Interacts with FBXO4 (PubMed:17081987). Interacts with UHRF2; the interaction ubiquitinates CCND1 and appears to occur independently of phosphorylation. Interacts with USP2. Interacts (via cyclin N-terminal domain) with INSM1 (via N-terminal region); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and inhibits CDK4 activity. Interacts with CDK4; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression (By similarity).|||Nucleus|||Nucleus membrane|||Phosphorylation at Thr-286 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex (By similarity). It also plays an essential role for recognition by the FBXO31 component of SCF (SKP1-cullin-F-box) protein ligase complex following DNA damage (By similarity).|||Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.|||Ubiquitinated at Lys-269 by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-286 phosphorylation (PubMed:33854232). The DCX(AMBRA1) complex represents the major regulator of CCND1 stability during the G1/S transition (PubMed:33854232). Also ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex containing FBXO4 and CRYAB (PubMed:17081987, PubMed:19767775). Following DNA damage it is ubiquitinated by some SCF (SKP1-cullin-F-box) protein ligase complex containing FBXO31. SCF-type ubiquitination is dependent on Thr-286 phosphorylation. Ubiquitinated also by UHRF2 apparently in a phosphorylation-independent manner. Ubiquitination leads to its degradation and G1 arrest. Deubiquitinated by USP2; leading to its stabilization (By similarity). http://togogenome.org/gene/10090:Sympk ^@ http://purl.uniprot.org/uniprot/Q80X82 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Symplekin family.|||Cell junction|||Cell membrane|||Found in a heat-sensitive complex at least composed of several cleavage and polyadenylation specific and cleavage stimulation factors. Interacts with CPSF2, CPSF3 and CSTF2. Interacts (via N-terminus) with HSF1; this interaction is direct and occurs upon heat shock. Interacts with SSU72.|||Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3'-end processing. Specific component of the tight junction (TJ) plaque, but might not be an exclusively junctional component. May have a house-keeping rule. Is involved in pre-mRNA polyadenylation. Enhances SSU72 phosphatase activity (By similarity).|||The HEAT repeats have been determined based on 3D-structure analysis of the D.melanogaster ortholog and are not detected by sequence-based prediction programs.|||cytoskeleton|||nucleoplasm|||tight junction http://togogenome.org/gene/10090:Med12 ^@ http://purl.uniprot.org/uniprot/A2AGH6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 12 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Also interacts with CTNNB1 and GLI3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ugt3a2 ^@ http://purl.uniprot.org/uniprot/Q8JZZ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||Highly expressed in kidney, while it is expressed at low levels in liver. Not detected in other tissues examined.|||Membrane|||UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity). http://togogenome.org/gene/10090:Myo6 ^@ http://purl.uniprot.org/uniprot/Q64331|||http://purl.uniprot.org/uniprot/Q8BK95 ^@ Caution|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Defects in Myo6 are the cause of Snell's waltzer, a condition characterized by circling, head-tossing, deafness and hyperactivity.|||Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding.|||Golgi apparatus|||Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding (By similarity). Able to function as a monomer under specific conditions in vitro (By similarity). Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells (By similarity). Component of the DISP/DOCK7-induced septin displacement complex, at least composed of DOCK7, LRCH3 and MYO6 (By similarity). Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal (By similarity). This interaction occurs only if the C-terminal lobe of calmodulin is occupied by calcium (By similarity). Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (By similarity). Interacts with DAB2 (PubMed:11906161). In vitro, the C-terminal globular tail binds a C-terminal region of DAB2 (PubMed:11906161). Interacts with CFTR (By similarity). Interacts with CABP5 (By similarity). Interacts (via residues 1128-1256) with TOM1 (via residues 392-463) (By similarity). Interacts (via residues 1060-1285) with OPTN (By similarity). Interacts (via residues 1060-1285) with TAX1BP1 and CALCOCO2/NDP52 (By similarity). Interacts with TOM1L2 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice display hearing loss, hyperactivity and circling behavior, suggesting vestibular defects. Higher steady state levels of LC3-II, indicating defciciency in autophagy (PubMed:23023224).|||Myosins are actin-based motor molecules with ATPase activity (PubMed:11906161). Unconventional myosins serve in intracellular movements (PubMed:11906161). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (By similarity). Has slow rate of actin-activated ADP release due to weak ATP binding (By similarity). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (By similarity). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (By similarity). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (By similarity). Together with TOM1, mediates delivery of endocytic cargo to autophagosomes thereby promoting autophagosome maturation and driving fusion with lysosomes (By similarity). Links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (By similarity). May act as a regulator of F-actin dynamics (By similarity). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (By similarity). May play a role in transporting DAB2 from the plasma membrane to specific cellular targets (PubMed:11906161). May play a role in the extension and network organization of neurites (PubMed:22039235). Required for structural integrity of inner ear hair cells (PubMed:7493015). Modulates RNA polymerase II-dependent transcription (By similarity).|||Nucleus|||Originally predicted to contain a coiled coil domain but generally accepted to contain a stable SAH domain instead.|||Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles and affects F-actin dynamics. Phosphorylated in vitro by p21-activated kinase (PAK).|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6).|||The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (By similarity). Its contribution to the mechanism confering the myosin movement on actin filaments is debated (By similarity).|||Within the cochlea, expressed specifically within the sensory hair cells (at protein level) (PubMed:7493015). Expressed in the inner and outer plexiform layer of the retina (at protein level) (PubMed:22039235). Widely expressed (PubMed:7493015). Expressed in the brain, kidney, liver, and testis (PubMed:7493015).|||clathrin-coated pit|||clathrin-coated vesicle|||cytosol|||filopodium|||microvillus|||perinuclear region|||ruffle membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gm21201 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or6z7 ^@ http://purl.uniprot.org/uniprot/Q60889 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Rbm22 ^@ http://purl.uniprot.org/uniprot/Q8BHS3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SLT11 family.|||Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex. Interacts with PDCD6; the interaction induces translocation of PDCD6 in the cytoplasm. Interacts with PPIL1 (By similarity).|||Cytoplasm|||Nucleus|||Required for pre-mRNA splicing as component of the activated spliceosome. Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.|||The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding. http://togogenome.org/gene/10090:Cnot6l ^@ http://purl.uniprot.org/uniprot/Q8VEG6 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCR4/nocturin family.|||Binds 2 magnesium ions, but the ions interact each with only 1 or 2 residues.|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8 (By similarity). Interacts with CNOT1, CNOT3, CNOT7, CNOT8 and CNOT9 (By similarity). Interacts with TOB1 (By similarity). Interacts with NANOS2 (PubMed:20133598). Interacts with ZFP36 (PubMed:21078877). Interacts with ZFP36L2 (By similarity). Interacts with RBM46 (PubMed:36001654).|||Cytoplasm|||Expressed in embryonic stem (ES) cells.|||Nucleus|||Poly(A) nuclease with 3'-5' RNase activity. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in mRNA decay mediated by the major-protein-coding determinant of instability (mCRD) of the FOS gene in the cytoplasm. Involved in deadenylation-dependent degradation of CDKN1B mRNA. Its mRNA deadenylase activity can be inhibited by TOB1. Mediates cell proliferation and cell survival and prevents cellular senescence (By similarity). http://togogenome.org/gene/10090:Vmn1r44 ^@ http://purl.uniprot.org/uniprot/Q9EQ47 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:L3hypdh ^@ http://purl.uniprot.org/uniprot/Q9CXA2 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the proline racemase family.|||Catalyzes the dehydration of trans-3-hydroxy-L-proline to delta-1-pyrroline-2-carboxylate (Pyr2C).|||Homodimer.|||In contrast to the T.cruzi proline racemase enzyme, lacks the conserved Cys at position 273 which is replaced by a Thr residue, transforming the racemase activity into dehydratase activity. http://togogenome.org/gene/10090:Or2y1g ^@ http://purl.uniprot.org/uniprot/Q8VFA7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dock4 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VLY2|||http://purl.uniprot.org/uniprot/P59764 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DOCK family.|||Cell membrane|||Expressed in inner ear (at protein level).|||Expressed in the utricular hair bundles at 14.5 dpc (at protein level) (PubMed:16464467). At P1 expressed in cochlear hair bundles of the sensory cells extending to the apical surface of the greater epithelial ridge and in the vestibule where it is restricted to hair bundles (at protein level) (PubMed:16464467).|||Functions as a guanine nucleotide exchange factor (GEF) that promotes the exchange of GDP to GTP, converting inactive GDP-bound small GTPases into their active GTP-bound form. Involved in regulation of adherens junction between cells. Plays a role in cell migration.|||Has a higher guanine nucleotide exchange factor activity compared to other isoforms.|||Interacts with nucleotide-free Rap1; functions as a guanine nucleotide exchange factor (GEF) for Rap1. Interacts (via DOCKER domain) with RAC1; functions as a guanine nucleotide exchange factor (GEF) for RAC1. Interacts with the SH3 domain of CRK. Interacts with FASLG. Interacts with ELMO2 and EPHA2; mediates activation of RAC1 by EPHA2. Interacts with USH1C (via PDZ 1 domain).|||The DOCKER domain mediates interaction with small GTPases like RAC1 and is required for their activation.|||cytosol http://togogenome.org/gene/10090:Eif4e1b ^@ http://purl.uniprot.org/uniprot/E9PVZ9|||http://purl.uniprot.org/uniprot/E9Q929|||http://purl.uniprot.org/uniprot/Q3UTA9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the eukaryotic initiation factor 4E family.|||EIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G (By similarity).|||Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. http://togogenome.org/gene/10090:Lamtor3 ^@ http://purl.uniprot.org/uniprot/O88653|||http://purl.uniprot.org/uniprot/Q542I7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:15263099). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (By similarity). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (By similarity). Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2 (PubMed:9733512).|||Belongs to the LAMTOR3 family.|||Endosome membrane|||Late endosome membrane|||Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer. The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability. The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (By similarity). Interacts with LAMTOR1 and LAMTOR2; the interaction is direct (PubMed:11266467, PubMed:15263099, PubMed:19177150). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with MAP2K1/MEK1 and MAPK2 (PubMed:9733512). Interacts with MORG1 (PubMed:15118098). http://togogenome.org/gene/10090:Mrpl37 ^@ http://purl.uniprot.org/uniprot/Q921S7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL37 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Or51v14 ^@ http://purl.uniprot.org/uniprot/E9PZ66 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Qpctl ^@ http://purl.uniprot.org/uniprot/Q8BH73 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glutaminyl-peptide cyclotransferase family.|||Detected in thalamus, hippocampus, brain cortex, cerebellum, kidney, lung and liver, and at low levels in heart and spleen.|||Golgi apparatus membrane|||It is unclear whether this protein requires a metal cofactor for catalysis. It was originally proposed to be a Zn(2+)-dependent metalloenzyme based on structural similarities to bacterial aminopeptidases and the observation that it can bind Zn(2+) ions, typically in a 1:1 stoichiometry (By similarity). However, a recent study suggests a Zn(2+)-independent catalytic mechanism (By similarity).|||Responsible for the biosynthesis of pyroglutamyl peptides. http://togogenome.org/gene/10090:Jazf1 ^@ http://purl.uniprot.org/uniprot/Q80ZQ5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2 (By similarity). Inhibits expression of the gluconeogenesis enzyme PCK2 through inhibition of NR2C2 activity (PubMed:24380856). Also involved in transcriptional activation of NAMPT by promoting expression of PPARA and PPARD (PubMed:24930994). Plays a role in lipid metabolism by suppressing lipogenesis, increasing lipolysis and decreasing lipid accumulation in adipose tissue (PubMed:24380856, PubMed:25614086). Plays a role in glucose homeostasis by improving glucose metabolism and insulin sensitivity (PubMed:25614086, PubMed:24380856).|||Expressed in range of tissues with highest expression levels in testis, liver, muscle and fat and lowest levels in kidney (PubMed:25614086). Detected in liver and white adipose tissue (at protein level) (PubMed:24380856).|||Expression is gradually but significantly up-regulated during adipocyte differentiation.|||Interacts with NR2C2 (via ligand-binding region).|||Nucleus http://togogenome.org/gene/10090:Bcl11b ^@ http://purl.uniprot.org/uniprot/Q99PV8 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain and thymus. Expressed in splenic CD4(+) T-lymphocytes (PubMed:16809611).|||Highly expressed in the developing embryo.|||Interacts with TFCOUP1, SIRT1, ARP1 and EAR2 (PubMed:10744719, PubMed:12930829). Interacts with EP300; the interaction is detected in activated T-lymphocytes, but not under resting conditions (By similarity).|||Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals (PubMed:12717433). Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (By similarity). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor protein involved in T-cell lymphomas. May function on the P53-signaling pathway. Repress transcription through direct, TFCOUP2-independent binding to a GC-rich response element.|||May be due to exon skipping.|||Nucleus|||Sumoylated with SUMO1. http://togogenome.org/gene/10090:Clcn1 ^@ http://purl.uniprot.org/uniprot/Q64347 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family. ClC-1/CLCN1 subfamily.|||Cell membrane|||Homodimer.|||Predominantly expressed in skeletal muscles.|||The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels (By similarity).|||Voltage-gated chloride channel (By similarity). Plays an important role in membrane repolarization in skeletal muscle cells after muscle contraction (Probable) (PubMed:8119941). http://togogenome.org/gene/10090:Kif1b ^@ http://purl.uniprot.org/uniprot/A2AH75|||http://purl.uniprot.org/uniprot/Q3UY61|||http://purl.uniprot.org/uniprot/Q60575 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Unc-104 subfamily.|||Expressed in the brain (at protein level).|||Isoform 1 mediates the transport of synaptic vesicles in neuronal cells.|||Mitochondrion|||Monomer (PubMed:7528108). Interacts with KIFBP (By similarity). Interacts (via C-terminus end of the kinesin-motor domain) with CHP1; the interaction occurs in a calcium-dependent manner (By similarity). Interacts with MADD (via death domain) (PubMed:18849981).|||Motor for anterograde transport of mitochondria. Has a microtubule plus end-directed motility.|||Reduced Rab3 and Madd levels in distal axons of hippocampal neurons.|||axon|||cytoskeleton|||synaptic vesicle http://togogenome.org/gene/10090:Dctpp1 ^@ http://purl.uniprot.org/uniprot/Q9QY93 ^@ Activity Regulation|||Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homotetramer.|||Hydrolyzes deoxynucleoside triphosphates (dNTPs) to the corresponding nucleoside monophosphates. Has a strong preference for dCTP and its analogs including 5-iodo-dCTP and 5-methyl-dCTP for which it may even have a higher efficiency. May protect DNA or RNA against the incorporation of these genotoxic nucleotide analogs through their catabolism.|||Inhibited by divalent calcium or cadmium ions.|||Probably binds two or three Mg(2+) ions per subunit.|||Ubiquitous. Highly expressed in heart, liver, skeletal muscle, cerebellum, brain, and salivary gland.|||cytosol http://togogenome.org/gene/10090:Acsm4 ^@ http://purl.uniprot.org/uniprot/Q80W40 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (By similarity). Capable of activating medium-chain fatty acids with a preference for C6-12 fatty acids (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Rpgr ^@ http://purl.uniprot.org/uniprot/Q9R0X5 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 3 isoform 1 is expressed in the retina in a narrow band at the developing photoreceptor layer; expression in this band persists through to postnatal day 14 but becomes severely diminished in the adult retina. Isoform 5 is first detected in the retina at postnatal day 14 and is expressed at increased levels in the adult retina (at protein level). Expressed throughout embryonic development from day 7 of gestation. Also expressed in adult.|||Could be a guanine-nucleotide releasing factor (By similarity). Plays a role in ciliogenesis (By similarity). Probably regulates cilia formation by regulating actin stress filaments and cell contractility (By similarity). May be involved in microtubule organization and regulation of transport in primary cilia (By similarity). Plays an important role in photoreceptor integrity. Isoform 5 may play a critical role in spermatogenesis and in intraflagellar transport processes.|||Expressed in the retina (at protein level) (PubMed:10401007, PubMed:22323458, PubMed:12140192, PubMed:16632484, PubMed:20007830, PubMed:21546531, PubMed:29899041). Isoforms 1: Expressed in the retina (at protein level) (PubMed:21546531). Isoform 5: Expressed in the retina (at protein level) (PubMed:20007830, PubMed:21546531). Expressed in the brain (PubMed:9677393, PubMed:10401007). Expressed in the testis (at protein level) (PubMed:10401007, PubMed:18579752). Expressed in kidney (at protein level) (PubMed:10401007, PubMed:20805823).|||Golgi apparatus|||In a mouse model of X-linked retinosa pigmentosa, where a 32bp duplication leads to a frameshift in the reading frame and a premature stop codon in isoform 5 (ORF15), mice exhibited retinal pathology including pigment loss and a slow progressive decrease in outer nuclear layer thickness.|||Interacts with SPATA7 (PubMed:29899041). Interacts with PDE6D (PubMed:9990021). Interacts with RPGRIP1 and RPGRIP1L; PDE6D, RPGRIP1 and RPGRIP1L may compete for the same binding sites (By similarity). Interacts with NPM1 (By similarity). Interacts with PDE6D. Isoform 5 interacts (via N-terminus) with SMC1A and SMC3 (PubMed:16043481). Isoform 5 interacts with CEP290 (PubMed:16632484). Interacts with WHRN (PubMed:22323458).|||Male BL/6 and BALB/c transgenic mice with an in-frame deletion of exon 4 of Rpgr show retinal degeneration that is rod or cone dominated, respectively.|||Male transgenic mice carrying multiple copies of the Rpgr transgene are infertile showing normal mating but no progeny; these mice also exhibit reduced sperm numbers as well as morphological and functional defects in the sperm flagellum.|||Overexpression of isoform 1 results in atypical accumulation of Rpgr in photoreceptor outer segments, abnormal photoreceptor morphology and severe retinal degeneration.|||Prenylated.|||The RCC1 repeat region mediates interactions with RPGRIP1.|||centrosome|||cilium|||cilium axoneme|||cilium basal body|||flagellum axoneme http://togogenome.org/gene/10090:Medag ^@ http://purl.uniprot.org/uniprot/Q14BA6 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Down-regulated by estrogen treatment.|||Highly expressed in white adipose tissue compared with other organs with higher expression in mature adipocyte fraction. Significant expression is also detected in the heart, brain, and pancreas.|||Involved in processes that promote adipocyte differentiation, lipid accumulation, and glucose uptake in mature adipocytes. http://togogenome.org/gene/10090:Begain ^@ http://purl.uniprot.org/uniprot/F8WIG2|||http://purl.uniprot.org/uniprot/Q68EF6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with DLG4 and DLGAP1 and forms a ternary complex.|||May sustain the structure of the postsynaptic density (PSD).|||Membrane http://togogenome.org/gene/10090:Mbd3 ^@ http://purl.uniprot.org/uniprot/Q9Z2D8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity). Acts as transcriptional repressor and plays a role in gene silencing (By similarity). Does not bind methylated DNA by itself (PubMed:9774669). Binds to a lesser degree DNA containing unmethylated CpG dinucleotides (By similarity). Recruits histone deacetylases and DNA methyltransferases (By similarity).|||Chromosome|||Heterodimer (via N-terminus) with MBD2 (By similarity). Component of the MeCP1 histone deacetylase complex (By similarity). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (By similarity). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (By similarity). Interacts with MBD3L2 (via N-terminus); the interaction is direct (By similarity). Interacts with BCL6 (By similarity). Interacts with CDK2AP1 (By similarity). Interacts with HDAC1 (By similarity). Interacts with MTA2 (By similarity). Interacts with DNMT1 (By similarity). Interacts with GATAD2A (By similarity). Interacts with GATAD2B (By similarity). Does not interact with PWWP2A (PubMed:30228260, PubMed:30327463). Does not interact with PWWP2B (PubMed:30228260).|||Highly expressed in brain, heart, kidney, liver, lung, skeletal muscle, spleen and testis. Detected at lower levels in embryonic stem cells.|||Nucleus http://togogenome.org/gene/10090:Hnrnph2 ^@ http://purl.uniprot.org/uniprot/P70333 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF. Interacts with TXNL4/DIM1.|||This protein is a component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Binds poly(RG) (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Fam167a ^@ http://purl.uniprot.org/uniprot/Q6P1G6 ^@ Similarity ^@ Belongs to the FAM167 (SEC) family. http://togogenome.org/gene/10090:Cldn24 ^@ http://purl.uniprot.org/uniprot/D3YXJ9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Yme1l1 ^@ http://purl.uniprot.org/uniprot/O88967 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent metalloprotease that catalyzes the degradation of folded and unfolded proteins with a suitable degron sequence in the mitochondrial intermembrane region (By similarity). Plays an important role in regulating mitochondrial morphology and function by cleaving OPA1 at position S2, giving rise to a form of OPA1 that promotes maintenance of normal mitochondrial structure (PubMed:17709429, PubMed:24616225, PubMed:26785494, PubMed:27495975). Ensures cell proliferation, maintains normal cristae morphology and complex I respiration activity, promotes antiapoptotic activity and protects mitochondria from the accumulation of oxidatively damaged membrane proteins (By similarity). Required for normal, constitutive degradation of PRELID1 (PubMed:26785494). Catalyzes the degradation of OMA1 in response to membrane depolarization. Required to control the accumulation of nonassembled respiratory chain subunits (NDUFB6, OX4 and ND1) (By similarity).|||Binds 1 zinc ion per subunit.|||Complete embryonic lethality; embryos present a clear developmental delay at 8.5 dpc, and the hearts of mutant embryos fail to beat properly at 9.5 and 10.5 dpc. Cardiomyocyte-specific gene disruption gives rise to animals that develop dilated cardiomyopathy and myocardial fibrosis at about 20 weeks after birth; mutants have a median life span of about 46 weeks, much shorter than wild-type. Mitochondria from mutant cardiomyocytes are smaller than normal, but have normal cristae architecture and display no significant difference in the assembly of respiratory complexes. Keeping mice with a cardiomyocyte-specific gene disruption on a high-fat diet leads to weight gain and reduced glucose tolerance, and prevents the development of cardiomyopathy. Mice with Yme1l gene disruption in cardiomyocytes and skeletal muscle have a median life span of 125 weeks, similar to wild-type. Their heart function is normal, in spite of the presence of fragmented mitochondria due to the loss of Opa1 cleavage at position S2. Skeletal muscle mitochondrial dysfunction is known to be associated with impaired insulin signaling and glucose intolerance, and as expected, these mice display impaired glucose homeostasis with decreased fasting insulin levels in the blood serum and glucose intolerance. Mice with a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 have normal cardiac function and do not display myocardial fibrosis. Likewise, cardiomyocyte mitochondria have normal morphology. Mice with a skeletal muscle Yme1l gene disruption plus a double, cardiomyocyte-specific gene disruption of Yme1l and Oma1 display normal glucose tolerance.|||Detected in heart and skeletal muscle (at protein level).|||Homohexamer; may also form heterohexamers. Exists in several complexes of 600-1100 kDa. Interacts with AFG1L.|||In the C-terminal section; belongs to the peptidase M41 family.|||In the N-terminal section; belongs to the AAA ATPase family.|||Mitochondrion|||Mitochondrion inner membrane|||Proteolytically processed by mitochondrial processing peptidase (MPP) to generate the mature form. http://togogenome.org/gene/10090:Vmn2r19 ^@ http://purl.uniprot.org/uniprot/G5E8G4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp3a25 ^@ http://purl.uniprot.org/uniprot/O09158 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:H2ap ^@ http://purl.uniprot.org/uniprot/Q9CR04 ^@ Subunit ^@ May interact with the N-terminus of HD. http://togogenome.org/gene/10090:Kng2 ^@ http://purl.uniprot.org/uniprot/Q6S9I0|||http://purl.uniprot.org/uniprot/Q6S9I2|||http://purl.uniprot.org/uniprot/Q6S9I3 ^@ Subcellular Location Annotation ^@ extracellular space http://togogenome.org/gene/10090:Nrgn ^@ http://purl.uniprot.org/uniprot/P60761 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the neurogranin family.|||Cytoplasm|||Disulfide bond formation is redox-sensitive. The cysteine residues are readily oxidized by several nitric acid (NO) donors and other oxidants to form intramolecular disulfide. Cys-51 can form a disulfide with any other of the cysteine residues with an order of reactivity Cys-9 > Cys-4 > Cys-3 (By similarity).|||Interacts with apo-calmodulin; this interaction decreases the affinity of calmodulin for calcium ions.|||Neurogranin is intrinsically unstructured; however, upon binding with CaM, The IQ domain adopts a helical conformation.|||Phosphorylated at Ser-36 by PHK and PKC, phosphorylation prevents interaction with Calmodulin and interrupts several learning- and memory-associated functions.|||Regulates the affinity of calmodulin for calcium. Involved in synaptic plasticity and spatial learning.|||Synapse|||dendritic spine http://togogenome.org/gene/10090:Stk19 ^@ http://purl.uniprot.org/uniprot/Q9JHN8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the STK19 family.|||Inactive serine/threonine-protein kinase.|||Nucleus http://togogenome.org/gene/10090:Gucy1a2 ^@ http://purl.uniprot.org/uniprot/F8VQK3|||http://purl.uniprot.org/uniprot/Q3TNN8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Cytoplasm http://togogenome.org/gene/10090:Ntsr2 ^@ http://purl.uniprot.org/uniprot/P70310 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Neurotensin receptor subfamily. NTSR2 sub-subfamily.|||Cell membrane|||Expressed maximally in the cerebellum, hippocampus, piriform cortex and neocortex of adult brain.|||Expressed poorly in 7-day-old brain. Expression increases at day 15 to reach a maximal level in 35-day-old brain.|||Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Zmym3 ^@ http://purl.uniprot.org/uniprot/Q9JLM4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I.|||Nucleus|||Plays a role in the regulation of cell morphology and cytoskeletal organization.|||Ubiquitously expressed in all embryonic stages and adult tissues. http://togogenome.org/gene/10090:Plekhm1 ^@ http://purl.uniprot.org/uniprot/Q7TSI1 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Acts as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Acts as a dual effector of RAB7A and ARL8B that simultaneously binds these GTPases, bringing about clustering and fusion of late endosomes and lysosomes. Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Interaction with Arl8b is a crucial factor in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (PubMed:27777970). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7. May have a role in sialyl-lex-mediated transduction of apoptotic signals (By similarity). Involved in bone resorption (PubMed:27777970).|||Autolysosome membrane|||Endosome membrane|||Interacts (via N- and C-terminus) with RAB7A (GTP-bound form). Simultaneously interacts with RAB7A and ARL8B; bringing about clustering and fusion of late endosomes and lysosomes. Interacts (via RUN domain) with ARL8B (GTP-bound form); the interaction is required for PLEKHM1 localization to lysosomes and for ARL8B function in delivery and degradation of endocytic and autophagic cargo in lysosomes. PLEKHM1 and PLEKHM2 compete for interaction with ARL8B. Interacts with ARL8A; the interaction is weaker than with ARL8B. Interacts with VPS41, VPS11, VPS18, VPS33A and VPS39; indicative for an association with the HOPS complex; the interactions with, at least, VPS41, VPS11, VPS18 and VPS33A require ARL8B (By similarity). Interacts with GABARAP, GABARAPL, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C (By similarity). Interacts with PAFAH1B (PubMed:22073305). Interacts (via N- and C-terminus) with NDEL1 (PubMed:27777970). Interacts (via C-terminus) with MAP3K7 (PubMed:27777970). Interacts (via N- and C-terminus) with FAM98A (PubMed:27777970). Interacts (via C-terminus) with DEF8; this interaction is weak but increased in a RAB7A-dependent manner (PubMed:27777970). May interact with sialyl-lex-positive protein (By similarity).|||Late endosome membrane|||Lysosome membrane|||Osteoclast-specific conditional knockout mice show normal tooth eruption, developed normally and are fertile, but trabecular bone mass in long bones and vertebrae is increased (PubMed:27777970). Osteoclast differentiation and number are normal, but bone resorption is decreased (PubMed:27777970). Show mislocalization of osteoclast lysosomes at the perinuclear area, instead at the cell periphery, and decreased ruffled border formation (PubMed:27777970).|||Sialyl-lex is a carcinoma associated antigen.|||The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and LC3A/B/C. http://togogenome.org/gene/10090:Tspo2 ^@ http://purl.uniprot.org/uniprot/Q9CRZ8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TspO/BZRP family.|||Cell membrane|||Cholesterol-binding protein involved in the redistribution of cholesterol from lipid droplets to the endoplasmic reticulum (PubMed:19729679, PubMed:32358067). Required to meet cholesterol demands during erythropoietic differentiation (PubMed:19729679, PubMed:32358067). May play a role in transport processes at the plasma membrane of erythrocytes, including regulating VDAC-mediated ATP export, and import of the heme precursors protoporphyrin IX and 5-aminolevulinic acid (By similarity).|||Decreases erythrocyte count and increases reticulocyte count (PubMed:32358067). Abnormal erythroblast cytokinesis and differentiation (PubMed:32358067). Decreases hemoglobin levels in maturing erythroid cells (PubMed:32358067).|||Endoplasmic reticulum membrane|||Expressed in liver, bone marrow and spleen. In spleen, detected in red pulp but not in white pulp.|||Homotetramer. May also form homodimer.|||Not expressed at 10.5 dpc. First detected at 12.5 dpc in the primordial liver (PubMed:19729679). Increased hepatic levels are found at 15.5 dpc followed by decline throughout newborn stage P1 and postnatal stages P5 and P10 with no hepatic expression in the adult (PubMed:19729679). In bone marrow, expressed during late gestation stages and remains elevated until adulthood (PubMed:19729679). In newborn and adult mice, also expressed in spleen (PubMed:19729679).|||The C-terminal region mediates cholesterol-binding. http://togogenome.org/gene/10090:Fzd1 ^@ http://purl.uniprot.org/uniprot/O70421 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation by specific Wnt family members may depend on the cells used for the experiment. Contradictory results have been reported for activation by WNT7B in human and mouse.|||Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Expressed in chondrocytes.|||Interacts with MYOC (By similarity). Interacts with WNT7B (PubMed:15923619).|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Receptor for Wnt proteins (PubMed:15923619). Activated by WNT7B (PubMed:15923619). Activated by WNT3A, WNT3, WNT1 and to a lesser extent WNT2, but apparently not by WNT4, WNT5A, WNT5B, WNT6, WNT7A or WNT7B (By similarity). Contradictory results showing activation by WNT7B have been described for mouse (PubMed:15923619). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:15923619). The canonical Wnt/beta-catenin signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (PubMed:15923619). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (Probable).|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:1700022I11Rik ^@ http://purl.uniprot.org/uniprot/Q3V0E1 ^@ Disruption Phenotype|||Function|||Tissue Specificity ^@ Dispensable for normal development and fertility.|||Expressed in kidney and testis (PubMed:36871790). Expressed at lower levels in stomach, intestine, epididymis and ovary (PubMed:36871790). Expressed at very low levels in heart and spleen (PubMed:36871790).|||No visible phenotype (PubMed:36871790). No effect on testis size, testis-to-body weight ratio, germ cell development or spermiogenesis (PubMed:36871790). No effect on sperm morphology, count or motility (PubMed:36871790). No effect on levels of germ cell apoptosis, chromosome H1t histone association or acrosome biogenesis (PubMed:36871790). http://togogenome.org/gene/10090:Slc19a2 ^@ http://purl.uniprot.org/uniprot/Q9EQN9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At embryonic stage 16.5 dpc detected in intestinal enterocytes, pancreatic acinar cells, and cochlear hair cells (at protein level). In newborn mice, detected in brain, kidney, liver and intestine (at protein level).|||Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.|||Cell membrane|||Expressed at low levels in liver and spleen.|||Expressed in liver (PubMed:24961373). Expressed in cochlear hair cells and duodenum (at protein level) (PubMed:11592824). Detected in pancreatic acinar cells (at protein level) (PubMed:22194418). Also expressed strongly in pancreatic islet cells (PubMed:22194418). Expressed in the testis (PubMed:14738878).|||High-affinity transporter for the intake of thiamine (PubMed:11481326, PubMed:11592824, PubMed:12393806, PubMed:22194418, PubMed:12031504, PubMed:24961373, PubMed:35724964). Essential for spermatogenesis (PubMed:14567973, PubMed:14738878). Mediates H(+)-dependent pyridoxine transport (PubMed:35512554, PubMed:35724964).|||Induced in a TP53/p53-dependent manner upon DNA damage.|||Males are infertile with reduced testis size and aspermia (PubMed:14567973, PubMed:14738878). Spermatogenesis fails at the pachytene spermatid stage with apoptosis of germ cells (PubMed:14567973, PubMed:14738878). When fed on a thiamine-free diet, animals develop additional phenotypes including diabetes mellitus, profound hearing loss, and defective hematopoiesis (PubMed:12393806, PubMed:14567973, PubMed:16642288). Pancreatic morphology appears to be normal although insulin secretion is significantly impaired (PubMed:12393806). Erythroid precursors in the bone marrow are almost completely absent leading to loss of reticulocytes in the peripheral blood (PubMed:14567973). The hearing loss phenotype is specifically associated with loss of cochlear inner hair cells (PubMed:16642288). These phenotypes can be reversed in many cases by re-introduction of a high thiamine diet (PubMed:12393806, PubMed:14567973, PubMed:16642288). Thiamine uptake by pancreatic acinar cells from knockout mice was found to be significantly lower than uptake by pancreatic acinar cells of the wild-type littermates (PubMed:22194418).|||Very highly expressed in liver, and also detected at lower levels in heart, testis, kidney, brain and spleen. http://togogenome.org/gene/10090:Lin52 ^@ http://purl.uniprot.org/uniprot/B2RQ11|||http://purl.uniprot.org/uniprot/Q8CD94 ^@ Similarity|||Subunit ^@ Belongs to the lin-52 family.|||Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity). http://togogenome.org/gene/10090:Angptl4 ^@ http://purl.uniprot.org/uniprot/Q9Z1P8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cleaved into a smaller N-terminal chain and a larger chain that contains the fibrinogen C-terminal domain; both cleaved and uncleaved forms are detected in the extracellular space. The cleaved form is not present within the cell.|||Detected in endothelial cells in the capillary plexus, veins and arteries in the retina at 2, 12 and 17 days after birth (PubMed:21832056). Expressed at low levels in most organs and connective tissue at 13.5 dpc. Between 15.5 dpc and 18.5 dpc, strongest expression in brown fat.|||Detected in liver and kidney (PubMed:10698685, PubMed:17609370). Predominantly expressed in adipose tissue and is strongly up-regulated by fasting in white adipose tissue and liver.|||Forms disulfide-linked dimers and tetramers.|||Homooligomer; disulfide-linked via Cys residues in the N-terminal part of the protein (PubMed:14583458). The homooligomer undergoes proteolytic processing to release the ANGPTL4 C-terminal chain, which circulates as a monomer. The homooligomer unprocessed form is able to interact with the extracellular matrix (By similarity).|||Induced in interstitial capillaries in response to hind leg ischemia (PubMed:17068295). Alterations in nutrition and leptin administration are found to modulate the expression in vivo.|||Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism (PubMed:15837923, PubMed:17609370, PubMed:29899519). May also play a role in regulating glucose homeostasis and insulin sensitivity (PubMed:15837923, PubMed:29899519). Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage (PubMed:14583458, PubMed:17130448, PubMed:21832056). Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro) (By similarity). Depending on context, may modulate tumor-related angiogenesis (Probable).|||Mediates inactivation of the lipoprotein lipase LPL, and thereby plays an important role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism. Has higher activity in LPL inactivation than the uncleaved protein.|||N-glycosylated.|||Pups are born at less than the expected Mendelian rate, indicative of significant embryonic lethality. No obvious phenotype after birth; mice are viable and fertile (PubMed:21832056). Mutant mice have reduced circulating triglyceride and cholesterol levels when fed a high-fat diet (PubMed:17609370, PubMed:29899519). Besides, they display 30% lower non-fasted blood glucose levels and improved glucose tolerance when fed a high-fat diet. In contrast, glucose levels and glucose tolerance are not different from wild-type when mice are kept on a normal diet (PubMed:29899519). The retinal vascular network displays subtle alterations, including a somewhat larger diameter of veins and capillaries. Pups display a delay in pericyte spreading on newly formed capillaries in the retina, and defects in the organization of endothelial cell tight junctions. In retinas from 17 day old animals, hypoxia-induced pathological neovascularization is strongly reduced (PubMed:21832056). Some studies observed decreased survival of suckling pups and of adults kept on a high-fat diet due to intestinal pathologies, with lipogranulomatous lesions of the intestines and their draining lymphatics and mesenteric lymph nodes (PubMed:17609370). Other studies observed no such effects (PubMed:29899519).|||Secreted|||Upon heterologous expression under the control of the keratinocyte promoter in the skin, inhibits tumor-associated angiogenesis and tumor growth (PubMed:14583458). In xenograft models, it inhibits both intra- and extravasation of tumor cells as well as vascular permeability leading to inhibition of metastases. Expression by tumor cells induces reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. It might prevent the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness (PubMed:17130448).|||extracellular matrix http://togogenome.org/gene/10090:Tssk3 ^@ http://purl.uniprot.org/uniprot/Q9D2E1 ^@ Activity Regulation|||Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Tissue Specificity ^@ Activated by phosphorylation on Thr-168, potentially by autophosphorylation.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Developmentally expressed in testicular germ cells. In adult testis, expression was detected in round and condensing spermatids, but not in meiotic pachytene spermatocytes. Not expressed in brain, ovary, kidney, liver or early embryonic cells.|||Expression begins 20-24 days after birth and is maximal in the adult. The pattern of expression suggests that STK22D is expressed postmeiotically.|||May be involved in a signaling pathway during male germ cell development or mature sperm function.|||PubMed:10781952 has termed the gene 'STK22D' as it was then thought that there were two different closely related genes. http://togogenome.org/gene/10090:Rhobtb3 ^@ http://purl.uniprot.org/uniprot/Q9CTN4 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Golgi apparatus|||Interacts with RAB9A and RAB9B (at lower level compared to RAB9A-binding). Interacts with M6PRBP1/TIP47 (By similarity).|||Rab9-regulated ATPase required for endosome to Golgi transport. Involved in transport vesicle docking at the Golgi complex, possibly by participating in release M6PRBP1/TIP47 from vesicles to permit their efficient docking and fusion at the Golgi. Specifically binds Rab9, but not other Rab proteins. Has low intrinsic ATPase activity due to autoinhibition, which is relieved by Rab9 (By similarity). http://togogenome.org/gene/10090:Ear6 ^@ http://purl.uniprot.org/uniprot/Q923L7 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Dnaaf11 ^@ http://purl.uniprot.org/uniprot/O88978 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At the embryonic day 8.0 dpc, expressed at the node, especially in pit cells, which are located at the central region of the node and possess motile cilia. At later stages, expression is detected in the notochord at 9.0 dpc, in the hindbrain, the branchial arches and neural tube at 11.0 dpc, in the hindbrain at 12.0 dpc and in the forebrain at 13.0 dpc.|||Belongs to the tilB family.|||Cytoplasm|||Dynein axonemal particle|||Interacts (via CS domain) with ZMYND10 (via C-terminus).|||Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia (PubMed:27353389). Acts as a crucial component in the formation and motility of spermatozoal flagella (By similarity).|||Mainly expressed in cells with motile cilia (PubMed:27353389). Expressed in epithelial cells of the trachea, testis and ependymal cells of the cerebral ventricles (PubMed:27353389). In testis, abundant expression in late prophase of meiosis I with a dramatic decrease after the first meiotic division (at protein level) (PubMed:10775177).|||Mutant mice show primary ciliary dyskinesia defects such as hydrocephalus and laterality defects and die within 5 weeks of birth. The morphology of mutant motile cilia is normal, but their motility is completely lost. The 9 + 2 arrangement of microtubules remain normal in mutants, but the outer dynein arms (ODAs) is absent from the cilia.|||cilium|||flagellum http://togogenome.org/gene/10090:Mix23 ^@ http://purl.uniprot.org/uniprot/E9Q4B5|||http://purl.uniprot.org/uniprot/F8WJI3|||http://purl.uniprot.org/uniprot/Q8R3Q6 ^@ Similarity ^@ Belongs to the MIX23 family. http://togogenome.org/gene/10090:Ubc ^@ http://purl.uniprot.org/uniprot/P0CG50 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ubiquitin family.|||Cytoplasm|||Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.|||For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.|||Mitochondrion outer membrane|||Mono-ADP-ribosylated at the C-terminus by PARP9, a component of the PPAR9-DTX3L complex. ADP-ribosylation requires processing by E1 and E2 enzymes and prevents ubiquitin conjugation to substrates such as histones.|||Nucleus|||Phosphorylated at Ser-65 by PINK1 during mitophagy. Phosphorylated ubiquitin specifically binds and activates parkin (PRKN), triggering mitophagy. Phosphorylation does not affect E1-mediated E2 charging of ubiquitin but affects discharging of E2 enzymes to form polyubiquitin chains. It also affects deubiquitination by deubiquitinase enzymes such as USP30.|||Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins eL40 and eS31, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains. http://togogenome.org/gene/10090:Tagln2 ^@ http://purl.uniprot.org/uniprot/Q9WVA4 ^@ Similarity ^@ Belongs to the calponin family. http://togogenome.org/gene/10090:Or51ab3 ^@ http://purl.uniprot.org/uniprot/A6H6I6|||http://purl.uniprot.org/uniprot/E9PYB4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ugt1a1 ^@ http://purl.uniprot.org/uniprot/Q63886 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||By dioxin.|||Endoplasmic reticulum membrane|||Highly expressed in liver and at lower levels in colon, kidney, stomach and intestine.|||Homodimers. Homooligomer. Interacts with UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers.|||UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (By similarity). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (By similarity). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (By similarity). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (By similarity). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (By similarity). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (By similarity). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (By similarity). http://togogenome.org/gene/10090:Mastl ^@ http://purl.uniprot.org/uniprot/Q8C0P0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Nucleus|||Phosphorylation at Thr-727 by CDK1 during M phase activates its kinase activity. Maximum phosphorylation occurs in prometaphase (By similarity).|||Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance. Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively. ARPP19 and ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved in checkpoint recovery by being inhibited (By similarity).|||centrosome http://togogenome.org/gene/10090:Mrps23 ^@ http://purl.uniprot.org/uniprot/Q8VE22 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS23 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Bcl7c ^@ http://purl.uniprot.org/uniprot/A0A0U1RNX8|||http://purl.uniprot.org/uniprot/O08664 ^@ Function|||Induction|||Similarity ^@ Belongs to the BCL7 family.|||Down-regulated by IL-10 in a malignant cell line derived from a murine model for chronic lymphocytic leukemia.|||May play an anti-apoptotic role. http://togogenome.org/gene/10090:Aldh5a1 ^@ http://purl.uniprot.org/uniprot/B2RS41|||http://purl.uniprot.org/uniprot/Q8BWF0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldehyde dehydrogenase family.|||Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).|||Homotetramer.|||Mitochondrion|||Redox-regulated. Inhibited under oxydizing conditions (By similarity). http://togogenome.org/gene/10090:Mrps21 ^@ http://purl.uniprot.org/uniprot/P58059|||http://purl.uniprot.org/uniprot/Q059G7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS21 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ifna6 ^@ http://purl.uniprot.org/uniprot/Q810G5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Sema5a ^@ http://purl.uniprot.org/uniprot/Q3UPZ0 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Glul ^@ http://purl.uniprot.org/uniprot/P15105 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamine synthetase family.|||Cell membrane|||Decamer; composed of two pentamers (By similarity). Interacts with PALMD (PubMed:16323283). Interacts with RHOJ (By similarity).|||Embryonic lethality when embryos move from the uterine tube to the uterine environment (PubMed:17557305). Conditional deletion in the liver leads to a marked increase of plasma ammonia levels, causing increased locomotion, impaired fear memory and a slightly reduced life span (PubMed:25870278). Conditional deletion in endothelial cells impairs vessel sprouting during vascular development due to defects in endothelial cell migration (PubMed:30158707).|||Expressed in microvascular endothelial cells.|||Glutamine synthetase activity is inhibited by methionine sulfoximine (MSO).|||Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (By similarity). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (PubMed:25870278). Essential for proliferation of fetal skin fibroblasts (By similarity). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development (PubMed:30158707). Involved in angiogenesis by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (By similarity). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (By similarity). Plays a role in ribosomal 40S subunit biogenesis (By similarity).|||Microsome|||Mitochondrion|||Palmitoylated; undergoes autopalmitoylation.|||Ubiquitinated by ZNRF1.|||cytosol http://togogenome.org/gene/10090:Gpr37l1 ^@ http://purl.uniprot.org/uniprot/A1L151|||http://purl.uniprot.org/uniprot/Q99JG2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 1, not detectable in any brain area examined but at postnatal day 8, strongly expressed in both astrocytes and oligodendrocyte precursors (OPs). At postnatal day 15 and during adulthood, expression in astrocytes and OPs remains at high levels.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||G-protein coupled receptor (PubMed:27072655). Has been shown to bind the neuroprotective and glioprotective factor prosaposin (PSAP), leading to endocytosis followed by an ERK phosphorylation cascade (By similarity). However, other studies have shown that prosaposin does not increase activity (By similarity). It has been suggested that GPR37L1 is a constitutively active receptor which signals through the guanine nucleotide-binding protein G(s) subunit alpha (By similarity). Participates in the regulation of postnatal cerebellar development by modulating the Shh pathway (PubMed:24062445). Regulates baseline blood pressure in females and protects against cardiovascular stress in males (PubMed:29625592). Mediates inhibition of astrocyte glutamate transporters and reduction in neuronal N-methyl-D-aspartate receptor activity (PubMed:28795439).|||Has been reported to act as a receptor for prosaposin (PSAP). However, it has also been shown that prosaposin does not increase activity. It has been suggested that GPR37L1 is a constitutively active receptor.|||Highly expressed in brain but not in heart or kidney (at protein level) (PubMed:29625592). In the brain, highly expressed in cerebellar Bergmann glia (at protein level) (PubMed:24062445, PubMed:29625592). Detected in the hippocampus but not in the brain stem or neocortex (at protein level) (PubMed:29625592). In several key cardiovascular centers of the central nervous system including the caudal and rostral ventrolateral medulla, the nucleus of the solitary tract, and the A5 nucleus, detected close to, but not within, tyrosine hydroxylase-positive catecholaminergic neurons (at protein level) (PubMed:29625592). Expressed in astrocytes in both gray and white matter and is also detected throughout the brain in some oligodendrocyte precursors (PubMed:28795439).|||Interacts with the PTCH1 receptor.|||Membrane|||Premature down-regulation of proliferation of cerebellar granule neuron precursors in postnatal mice, precocious maturation of Bergmann glia and Purkinje neurons, precocious juvenile motor abilities, and improved adult motor learning and coordination (PubMed:24062445). Early activation of the Shh pathway with increased levels of Shh, Smo and Ptch1 earlier in postnatal development than in wild-type mice (PubMed:24062445). Increased aortic diastolic, mean arterial and pulse pressures in females but not in males (PubMed:29625592). Males develop exacerbated left ventricular hypertrophy and evidence of heart failure when challenged with short-term angiotensin-2 infusion while females are protected from cardiac fibrosis (PubMed:29625592). Increased susceptibility to induced seizures (PubMed:28688853). Reduced signaling in the cerebellum as indicated by significantly less cAMP production (PubMed:27072655). No effect on the input resistance or resting potential of astrocytes or neurons (PubMed:28795439). Neuronal death is increased by 40% in an in vitro model of ischemia (PubMed:28795439).|||The N-terminal region is required for constitutive signal transduction.|||Ubiquitinated.|||Undergoes metalloprotease-mediated cleavage which reduces its constitutive activity.|||cilium membrane http://togogenome.org/gene/10090:Nop58 ^@ http://purl.uniprot.org/uniprot/Q6DFW4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOP5/NOP56 family.|||Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles; the core proteins SNU13, NOP56, NOP58 and FBL assemble stepwise onto the snoRNA (PubMed:10864044). Interacts with NOLC1/Nopp140. Interacts with NOPCHAP1, NUFIP1, RUVBL1 and RUVBL2; NOPCHAP1 bridges the association of NOP58 with RUVBL1:RUVBL2 and NUFIP1. Interacts with PIH1D1.|||Required for 60S ribosomal subunit biogenesis (By similarity). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. Required for the biogenesis of box C/D snoRNAs such as U3, U8 and U14 snoRNAs (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Sumoylation is essential for high-affinity binding to snoRNAs.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Zfp583 ^@ http://purl.uniprot.org/uniprot/Q3V080 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Kif22 ^@ http://purl.uniprot.org/uniprot/Q3V300 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Interacts with FAM83D and SIAH1.|||Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA. Plays a role in congression of laterally attached chromosomes in NDC80-depleted cells.|||Nucleus|||Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation.|||cytoskeleton http://togogenome.org/gene/10090:Lman2 ^@ http://purl.uniprot.org/uniprot/Q9DBH5 ^@ Cofactor|||Function|||Subcellular Location Annotation ^@ Binds 2 calcium ions per subunit.|||Golgi apparatus membrane|||Plays a role as an intracellular lectin in the early secretory pathway. Interacts with N-acetyl-D-galactosamine and high-mannose type glycans and may also bind to O-linked glycans. Involved in the transport and sorting of glycoproteins carrying high mannose-type glycans (By similarity). http://togogenome.org/gene/10090:Ubash3b ^@ http://purl.uniprot.org/uniprot/Q8BGG7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in splenic T-cells and B-cells, total spleen, skeletal muscle, heart, lung, kidney, thymus, brain and liver (at protein level). Highly expressed in brain. Detected in heart, spleen, lung, liver, kidney and testis.|||Homodimer (PubMed:20516590, PubMed:17679096). Interacts with JAK2 (in vitro) (PubMed:12370296). Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins (By similarity). Interacts with ZAP70 (ubiquitinated form) (PubMed:26903241).|||Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.|||Mice display strikingly elevated levels of tyrosine phosphorylated, ubiquitinated proteins following TCR stimulation. They are prothrombotic and have shorter bleeding times, which is attributed to insufficient SYK dephosphorylation in platelets.|||Nucleus http://togogenome.org/gene/10090:Or10h1 ^@ http://purl.uniprot.org/uniprot/A0PK55 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r65 ^@ http://purl.uniprot.org/uniprot/G3X931 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm4952 ^@ http://purl.uniprot.org/uniprot/Q5FW57 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycine N-acyltransferase family.|||Mitochondrial acyltransferase which transfers the acyl group to the N-terminus of glycine. Can conjugate a multitude of substrates to form a variety of N-acylglycines (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Fosb ^@ http://purl.uniprot.org/uniprot/P13346 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. Fos subfamily.|||Binds DNA via bZIP domain; DNA-binding is under control of cellular redox homeostasis (in vitro) (By similarity). To enable DNA binding, the bZIP domain must undergo a conformational rearrangement which requires the reduction of the interchain disulfide bond between FosB and JunD (in vitro) (By similarity). The bZIP domain is able to form homomeric oligomers via formation of interchain disulfide bonds under non-reducing conditions (in vitro) (By similarity). Under reducing conditions, the disulfide-bonded homomeric species dissociates into monomers (in vitro) (By similarity).|||Deficiency in the ability to nurture young animals and the majority of pups die within 1-2 days of birth (PubMed:8706134). Impaired nurturing behavior towards newborns is observed in postpartum mothers as well as in young females and males (PubMed:8706134). Failure in AP-1 binding activity after repeated cocaine administration (PubMed:9294222). Exaggerated locomotor activation in response to initial cocaine exposures as well as robust conditioned place preference to a lower dose of cocaine, but lack of increment in cocaine-induced hyperactivity over 6 days (i.e. sensitization) (PubMed:9294222). Decreased sensitivity to rewarding properties of morphine and spatial memory impairment (PubMed:18407360). Decreased proliferation and increased ectopic migration of neural progenitor cells in the hippocampus (PubMed:23303048). Exhibit impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior (PubMed:23303048). Altered gene expression in the hippocampus, including genes implicated in neurogenesis, depression, or epilepsy (PubMed:23303048). Knockout in hippocampal neurons, including neurons of the subgranular zone of the dentate gyrus, leads to a reduction of antidepressant-induced neurogenesis and impedes hippocampus-dependent learning in the novel object recognition task (PubMed:30902680).|||Exhibits lower transactivation activity than isoform 1 in vitro (PubMed:17241283). The heterodimer with JUN does not display any transcriptional activity, and may thereby act as an transcriptional inhibitor (PubMed:1900040). May be involved in the regulation of neurogenesis in the hippocampus (PubMed:23303048). May play a role in synaptic modifications in nucleus accumbens medium spiny neurons and thereby play a role in adaptive and pathological reward-dependent learning, including maladaptive responses involved in drug addiction (PubMed:23319622). Seems to be more stably expressed with a half-life of ~9.5 hours in cell culture as compared to 1.5 hours half-life of isoform 1 (PubMed:18407360).|||Expressed in brain, including the preoptic area of the hypothalamus, the main and accessory olfactory bulbs, the pyriform cortex and the hippocampus (at protein level) (PubMed:8706134, PubMed:23303048). Expressed in the neurons of the subgranular zone of the dentate gyrus in the hippocampus (at protein level) (PubMed:23303048, PubMed:30902680). Expressed in pyramidal cells in CA1 and CA3, in the dentate gyrus and the nucleus accumbens of the striatum (at protein level) (PubMed:9294222, PubMed:26446228).|||Expressed in the core and shell of the nucleus accumbens of the striatum (at protein level) (PubMed:20473292). Expressed in the neurons of the subgranular zone of the dentate gyrus in the hippocampus (at protein level) (PubMed:23303048).|||Heterodimer; binds to DNA as heterodimer (PubMed:2498083, PubMed:1900040). Component of an AP-1 transcription factor complex; composed of FOS-JUN heterodimers (PubMed:2498083, PubMed:1900040). As part of the AP-1 transcription factor complex, forms heterodimers with JUN, JUNB or JUND, thereby binding to the AP-1 consensus sequence and stimulating transcription (PubMed:2498083, PubMed:1900040). Interacts with the BAF multiprotein chromatin-remodeling complex subunits SMARCB1 and SMARCD1 (PubMed:29272704). Interacts with ARID1A and JUN (PubMed:29272704).|||Heterodimerizes with proteins of the JUN family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to gene promoters containing an AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing their transcriptional activity (PubMed:2498083, PubMed:1900040). As part of the AP-1 complex, facilitates enhancer selection together with cell-type-specific transcription factors by collaboratively binding to nucleosomal enhancers and recruiting the SWI/SNF (BAF) chromatin remodeling complex to establish accessible chromatin (PubMed:29272704). Together with JUN, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway (By similarity). Exhibits transactivation activity in vitro (PubMed:17241283). Involved in the display of nurturing behavior towards newborns (PubMed:8706134). May play a role in neurogenesis in the hippocampus and in learning and memory-related tasks by regulating the expression of various genes involved in neurogenesis, depression and epilepsy (PubMed:23303048, PubMed:30902680). Implicated in behavioral responses related to morphine reward and spatial memory (PubMed:9294222, PubMed:18407360).|||Homodimer under oxidizing conditions and monomer under reducing conditions (in vitro) (By similarity). Heterodimer; binds to DNA as heterodimer (PubMed:1900040). Forms heterodimers with JUNB, JUN or JUND; thereby binding to the AP-1 consensus sequence but does not stimulate transcription (PubMed:1900040). Forms heterodimers with JUND under oxidizing conditions (By similarity).|||Induced by cocaine in the striatum (PubMed:9294222). Induced by chronic social defeat stress, with resilient mice showing the greatest induction in both core and shell nucleus accumbens subregions (PubMed:20473292).|||Induced by cocaine in the striatum.|||Induced by growth factors (PubMed:2498083). Up-regulated in the preoptic area of the hypothalamus after 6 hours of exposure to pups (PubMed:8706134). Induced by cocaine in the striatum (PubMed:9294222). Induced by kainic acid (PubMed:23303048). Induced in the hippocampus by novelty exposure and spatial learning (PubMed:26446228).|||Nucleus|||Phosphorylated at Ser-27 by CSNK2A1; phosphorylation increases protein stability and transactivation potential.|||Phosphorylated. http://togogenome.org/gene/10090:Smr3a ^@ http://purl.uniprot.org/uniprot/Q61900 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PROL1/PROL3 family.|||May play a role in protection or detoxification.|||Secreted|||Secreted into saliva by submaxillary gland. http://togogenome.org/gene/10090:Pde1b ^@ http://purl.uniprot.org/uniprot/A0A2I3BPC1|||http://purl.uniprot.org/uniprot/Q01065|||http://purl.uniprot.org/uniprot/Q6PDS5|||http://purl.uniprot.org/uniprot/Q9DBS6 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.|||Cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. Has a preference for cGMP as a substrate.|||Homodimer.|||Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+).|||cytosol http://togogenome.org/gene/10090:Adam23 ^@ http://purl.uniprot.org/uniprot/Q9R1V7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain specific.|||Can bind to LGI1 and LGI4.|||Cell membrane|||May play a role in cell-cell and cell-matrix interactions. This is a non-catalytic metalloprotease-like protein (By similarity).|||On 15 dpc embryo the level of isoform Gamma exceeded that of isoform Alpha and isoform Beta and decreased after birth. On P10 post neonatal, the level of isoform Gamma is undetectable and isoform Alpha and isoform Beta are expressed again.|||Secreted http://togogenome.org/gene/10090:Timm13 ^@ http://purl.uniprot.org/uniprot/P62075 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small Tim family.|||Heterohexamer; composed of 3 copies of TIMM8 (TIMM8A or TIMM8B) and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22 (By similarity).|||Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins (By similarity).|||Mitochondrion inner membrane|||Present at high level in liver and brain, and at lower level in muscle and heart. In CNS sections, it is predominantly present in the soma and the dendritic portion of the Purkinje cells of the cerebellum, but not in the glial cells. Scattered expression also is also detected in the brain stem, olfactory bulb, substantia nigra, hippocampus and striatum (at protein level).|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM13 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). http://togogenome.org/gene/10090:Igsf9 ^@ http://purl.uniprot.org/uniprot/Q05BQ1 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. Turtle family.|||Cell membrane|||Detected in brain during embryonic development at least from 7.5 dpc until 16.5 dpc. Mainly expressed within the dorsal root glanglia, trigeminal glanglia and olfactory epithelium of 10.5 dpc embryos. Expressed to a lower extent in neuroepithelium, retina and hindgut.|||Expressed in both cell bodies and dendrites of cortical and hippocampal neurons and also cerebellar Purkinje cells (at protein level).|||Functions in dendrite outgrowth and synapse maturation.|||Interacts with MAGI2 and SHANK1.|||Synapse|||The PDZ-binding motif mediates interactions with MAGI2 and SHANK1. http://togogenome.org/gene/10090:BC016579 ^@ http://purl.uniprot.org/uniprot/Q8C5C9 ^@ Subcellular Location Annotation ^@ Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Pld6 ^@ http://purl.uniprot.org/uniprot/Q5SWZ9 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholipase D family. MitoPLD/Zucchini subfamily.|||Cell membrane|||Evidence for subcellular location in the Golgi was determined in pachytene spermatocytes and spermatids in mouse testes. They observe that the ectopically expressed PLD6 protein was localized to the mitochondria in PLD6-transfected cells. Authors claim a possible explanation for the contradictory results is that previous studies have reported the localization of exogenous PLD6, but not endogenous PLD6, in cultured cells. The reason for differences observed in subcellular localization of exogenous and endogenous PLD6 is not clear but one attributable reason may be that different types of anti-PLD6 antibodies have been used in previous studies.|||Expressed in embryonic testis at 16.5 dpc (at protein level). Expressed at low levels in type A and B spermatogonia, increases 5-fold in spermatocytes undergoing meiosis (pachytene spermatocytes), and then decreases again in round spermatids. Expressed at low levels in testes in young mice, peaks from postnatal day 14 to day 29 with the onset of puberty andpersists in adulthood (at protein level).|||Golgi apparatus|||Homodimer (PubMed:23064227). Interacts with MOV10L1 (PubMed:25762440). Interacts with MIGA1 and MIGA2; possibly facilitating homodimer formation (By similarity). Interacts with GK2 (PubMed:28852571).|||In contrast to other members of the phospholipase D family, contains only one PLD phosphodiesterase domain, suggesting that it has a single half-catalytic and requires homodimerization to form a complete active site.|||Males are sterile, because of meiotic arrest during spermatogenesis due to demethylation and subsequent derepression of transposable elements. No spermatids were observed in the mutant testes, and no spermatozoon in the epididymis. Effects are caused by defects in primary piRNA biogenesis: in contrast to wild-type cells neither mitochondria nor associated meiotic nuage (named P granule) are aggregated.|||Mitochondrion outer membrane|||Nucleus membrane|||Predominantly expressed in testis (at protein level) and in growing ovary (PubMed:21397847, PubMed:33783608). Also expressed in the brain, eye and urinary bladder (at protein level), but its levels were low or undetectable in other organs (PubMed:33783608).|||Presents phospholipase and nuclease activities, depending on the different physiological conditions. Interaction with Mitoguardin (MIGA1 or MIGA2) affects the dimer conformation, facilitating the lipase activity over the nuclease activity. Plays a key role in mitochondrial fusion and fission via its phospholipase activity. In its phospholipase role, it uses the mitochondrial lipid cardiolipin as substrate to generate phosphatidate (PA or 1,2-diacyl-sn-glycero-3-phosphate), a second messenger signaling lipid. Production of PA facilitates Mitofusin-mediated fusion, whereas the cleavage of PA by the Lipin family of phosphatases produces diacylgycerol (DAG) which promotes mitochondrial fission. Both Lipin and DAG regulate mitochondrial dynamics and membrane fusion/fission, important processes for adapting mitochondrial metabolism to changes in cell physiology. Mitochondrial fusion enables cells to cope with the increased nucleotide demand during DNA synthesis (By similarity). Mitochondrial function and dynamics are closely associated with biological processes such as cell growth, proliferation, and differentiation (PubMed:21397848). Mediator of MYC activity, promotes mitochondrial fusion and activates AMPK which in turn inhibits YAP/TAZ, thereby inducing cell growth and proliferation (PubMed:26678338). The endonuclease activity plays a critical role in PIWI-interacting RNA (piRNA) biogenesis during spermatogenesis (PubMed:21397847, PubMed:21397848). Implicated in spermatogenesis and sperm fertility in testicular germ cells, its single strand-specific nuclease activity is critical for the biogenesis/maturation of PIWI-interacting RNA (piRNA) (PubMed:21397847, PubMed:23064230, PubMed:23064227). MOV10L1 selectively binds to piRNA precursors and funnels them to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins (PubMed:25762440). Cleaves either DNA or RNA substrates with similar affinity, producing a 5' phosphate end, in this way it participates in the processing of primary piRNA transcripts. piRNAs provide essential protection against the activity of mobile genetic elements. piRNA-mediated transposon silencing is thus critical for maintaining genome stability, in particular in germline cells when transposons are mobilized as a consequence of wide-spread genomic demethylation (PubMed:23064230, PubMed:23064227). PA may act as signaling molecule in the recognition/transport of the precursor RNAs of primary piRNAs (PubMed:21397847). Interacts with tesmin in testes, suggesting a role in spermatogenesis via association with its interacting partner (PubMed:33783608).|||Single stranded DNA (ssDNA) hydrolase activity does not depend upon, but is stimulated by the presence of Ca(2+) and Mn(2+) (PubMed:23064227). MIGA1 and MIGA2 increase PLD6 self-association affinity and affects the homodimer conformation facilitating its phospholipase activity over the nuclease activity. MYC induces its expression and stimulates its phospholipase activity (By similarity). http://togogenome.org/gene/10090:Gpr143 ^@ http://purl.uniprot.org/uniprot/P70259 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the G-protein coupled receptor OA family.|||Glycosylated.|||Interacts with heterotrimeric G(i) proteins. Interacts with ARRB1 and ARRB2. Interacts with MLANA (By similarity).|||Lysosome membrane|||Melanosome membrane|||Phosphorylated.|||Receptor for tyrosine, L-DOPA and dopamine. After binding to L-DOPA, stimulates Ca(2+) influx into the cytoplasm, increases secretion of the neurotrophic factor SERPINF1 and relocalizes beta arrestin at the plasma membrane; this ligand-dependent signaling occurs through a G(q)-mediated pathway in melanocytic cells. Its activity is mediated by G proteins which activate the phosphoinositide signaling pathway. Also plays a role as an intracellular G protein-coupled receptor involved in melanosome biogenesis, organization and transport.|||The cytoplasmic domain 3 and the C-terminus tail domain contain the lysosomal sorting signals and are necessary and sufficient for intracellular retention and delivery to lysosomal and melanosomal, respectively in melanocytic and non-melanocytic cells. http://togogenome.org/gene/10090:Ctag2l1 ^@ http://purl.uniprot.org/uniprot/A3KG45 ^@ Similarity ^@ Belongs to the CTAG/PCC1 family. http://togogenome.org/gene/10090:Or11n2 ^@ http://purl.uniprot.org/uniprot/Q7TQW3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnf17 ^@ http://purl.uniprot.org/uniprot/Q99MV7 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed at high levels in adult testis. Expressed in male germ cells (at protein level). Expressed at lower levels in adult thyroid, submaxillary gland, ovary and epididymis.|||Interacts with MXD1, MXD3, MXD4, MXI1 and PIWIL1. Self-associates.|||Major.|||Male mice are sterile, exhibit a complete arrest in round spermatids and fail to produce sperm.|||Nucleus|||Seems to be involved in regulation of transcriptional activity of MYC. In vitro, inhibits DNA-binding activity of Mad-MAX heterodimers. Can recruit Mad transcriptional repressors (MXD1, MXD3, MXD4 and MXI1) to the cytoplasm. May be involved in spermiogenesis. http://togogenome.org/gene/10090:Hdac10 ^@ http://purl.uniprot.org/uniprot/Q6P3E7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the histone deacetylase family. HD type 2 subfamily.|||Cytoplasm|||Interacts with HDAC3. Interacts with HDAC2 and NCOR2/SMRT. Interacts with HSPA8/HSC70. Interacts with MSH2.|||Nucleus|||Polyamine deacetylase (PDAC), which acts preferentially on N(8)-acetylspermidine, and also on acetylcadaverine and acetylputrescine. Exhibits attenuated catalytic activity toward N(1),N(8)-diacetylspermidine and very low activity, if any, toward N(1)-acetylspermidine. Histone deacetylase activity has been observed in vitro. Has also been shown to be involved in MSH2 deacetylation. The physiological relevance of protein/histone deacetylase activity is unclear and could be very weak. May play a role in the promotion of late stages of autophagy, possibly autophagosome-lysosome fusion and/or lysosomal exocytosis in neuroblastoma cells. May play a role in homologous recombination. May promote DNA mismatch repair.|||Protein/histone deacetylase activity in vivo is uncertain. The 3D structure analysis of the zebrafish ortholog shows that a glutamate gatekeeper and a sterically constricted active site confer specificity for N(8)-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Supporting this observation, has been shown to exhibit only very low activity, if any, towards acetyl-lysine peptide substrates. However, histone deacetylase activity has been observed in vitro and HDAC10 has also been shown to be involved in MSH2 deacetylation.|||widely expressed. http://togogenome.org/gene/10090:Pigw ^@ http://purl.uniprot.org/uniprot/B7ZN11|||http://purl.uniprot.org/uniprot/Q8C398 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGW family.|||Endoplasmic reticulum membrane|||Membrane|||Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor.|||Required for the transport of GPI-anchored proteins to the plasma membrane. Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor. Acetylation during GPI-anchor biosynthesis is not essential for the subsequent mannosylation and is usually removed soon after the attachment of GPIs to proteins. http://togogenome.org/gene/10090:Cep85 ^@ http://purl.uniprot.org/uniprot/Q8BMK0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a negative regulator of NEK2 to maintain the centrosome integrity in interphase. Suppresses centrosome disjunction by inhibiting NEK2 kinase activity.|||Belongs to the CEP85 family.|||centrosome|||nucleolus|||spindle pole http://togogenome.org/gene/10090:Btbd9 ^@ http://purl.uniprot.org/uniprot/Q8C726 ^@ Tissue Specificity ^@ Expressed in the brain (at protein level). http://togogenome.org/gene/10090:Rapsn ^@ http://purl.uniprot.org/uniprot/P12672 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer.|||Belongs to the RAPsyn family.|||Cell membrane|||Postsynaptic cell membrane|||Postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. It may link the receptor to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin (By similarity).|||Ubiquitinated by the BCR(KLHL8) complex, leading to its degradation.|||cytoskeleton http://togogenome.org/gene/10090:Gm21249 ^@ http://purl.uniprot.org/uniprot/Q810R8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Obi1 ^@ http://purl.uniprot.org/uniprot/Q8K2Y0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Associates with ORC complex. Binds to chromatin; association is cell cycle-regulated, absent from mitotic chromosomes, is associated with chromatin from G1 and partially released from chromatin from mid S-phase.|||Auto-ubiquitinated.|||Chromosome|||E3 ubiquitin ligase essential for DNA replication origin activation during S phase. Acts as a replication origin selector which selects the origins to be fired and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase. http://togogenome.org/gene/10090:Fmn2 ^@ http://purl.uniprot.org/uniprot/Q9JL04 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein that is involved in actin cytoskeleton assembly and reorganization (PubMed:18848445, PubMed:21620703). Acts as an actin nucleation factor and promotes assembly of actin filaments together with SPIRE1 and SPIRE2 (PubMed:18848445, PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (PubMed:21983562). Required for asymmetric spindle positioning, asymmetric oocyte division and polar body extrusion during female germ cell meiosis (PubMed:12447394, PubMed:18848445, PubMed:19062278, PubMed:21620703). Plays a role in responses to DNA damage, cellular stress and hypoxia by protecting CDKN1A against degradation, and thereby plays a role in stress-induced cell cycle arrest (By similarity). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (By similarity). Protects cells against apoptosis by protecting CDKN1A against degradation (By similarity).|||Belongs to the formin homology family. Cappuccino subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Detected in brain and in oocytes (at protein level) (PubMed:12447394, PubMed:19062278). Expressed almost exclusively in the developing and mature central nervous system (PubMed:10781961). Detected in oocytes (PubMed:12447394, PubMed:19062278).|||Expression begins at embryonic day 9.5 in the developing spinal cord and brain structures and continues in neonatal and adult brain structures including the olfactory bulb, cortex, thalamus, hypothalamus, hippocampus and cerebellum.|||Interacts with SPIRE1 (PubMed:21705804). Binds actin (PubMed:21705804). Interacts with CDKN1A (By similarity).|||No visible phenotype in male mice, but female mice show reduced fertility and produce at most one to three pups per litter (PubMed:12447394). Female mice display defects in asymmetric spindle positioning, asymmetric cell division and polar body extrusion during oocyte meiosis (PubMed:12447394). During early pregnancy, females present normal numbers of implantation sites, but only very few normal-looking embryos (PubMed:12447394). Most of the embryos show developmental delays and gross morphological defects, leading to embryonic death (PubMed:12447394).|||Nucleus|||cell cortex|||cytoskeleton|||cytosol|||nucleolus|||perinuclear region http://togogenome.org/gene/10090:Fmo1 ^@ http://purl.uniprot.org/uniprot/P50285|||http://purl.uniprot.org/uniprot/Q3UNX7|||http://purl.uniprot.org/uniprot/Q8C9C1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FMO family.|||Broad spectrum monooxygenase that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including xenobiotics (PubMed:9580872, PubMed:32156684). Catalyzes the S-oxygenation of hypotaurine to produce taurine, an organic osmolyte involved in cell volume regulation as well as a variety of cytoprotective and developmental processes (PubMed:32156684). In vitro, catalyzes the N-oxygenation of trimethylamine (TMA) to produce trimethylamine N-oxide (TMAO) and could therefore participate to the detoxification of this compound that is generated by the action of gut microbiota from dietary precursors such as choline, choline containing compounds, betaine or L-carnitine (By similarity).|||Endoplasmic reticulum membrane|||Liver.|||Membrane http://togogenome.org/gene/10090:Pde7b ^@ http://purl.uniprot.org/uniprot/E9Q0W7|||http://purl.uniprot.org/uniprot/Q8CBS2|||http://purl.uniprot.org/uniprot/Q9QXQ1 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE7 subfamily.|||Binds 2 divalent metal cations per subunit (By similarity). Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions (By similarity).|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.|||Highly expressed in brain.|||Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:10872825). May be involved in the control of cAMP-mediated neural activity and cAMP metabolism in the brain (By similarity).|||Inhibited by dipyridamole, IBMX and SCH 51866. Insensitive to zaprinast, rolipram, and milrinone. http://togogenome.org/gene/10090:Sec14l2 ^@ http://purl.uniprot.org/uniprot/Q99J08 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity to other tocopherols and to tocotrienols. May have a transcriptional activatory activity via its association with alpha-tocopherol. Probably recognizes and binds some squalene structure, suggesting that it may regulate cholesterol biosynthesis by increasing the transfer of squalene to a metabolic active pool in the cell (By similarity).|||Cytoplasm|||Monomer.|||Nucleus http://togogenome.org/gene/10090:Zbtb48 ^@ http://purl.uniprot.org/uniprot/Q1H9T6 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with EP300.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Telomere-binding protein that acts as a regulator of telomere length. Directly binds the telomeric double-stranded 5'-TTAGGG-3' repeat. Preferentially binds to telomeres that have a low concentration of shelterin complex and acts as a regulator of telomere length by initiating telomere trimming, a process that prevents the accumulation of aberrantly long telomeres. Also acts as a transcription regulator that binds to promoter regions. Regulates expression of a small subset of genes, including MTFP1. Regulates expression the J and/or S elements in MHC II promoter. Acts as a negative regulator of cell proliferation by specifically activating expression of ARF, a tumor suppressor isoform of CDKN2A.|||The C2H2-type zinc fingers mediate binding to the telomeric double-stranded 5'-TTAGGG-3' repeats. The last C2H2-type zinc finger is required for telomeric-binding.|||telomere http://togogenome.org/gene/10090:Rab7 ^@ http://purl.uniprot.org/uniprot/P51150 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasmic vesicle|||Deubiquitination at Lys-191 and Lys-194 by USP32.|||Endosome membrane|||Expressed in the dorsal root ganglia and the sciatic nerve at 13.5 dpc (at protein level).|||Interacts with NTRK1/TRKA (By similarity), RILP (By similarity), PSMA7 (By similarity), RNF115 (PubMed:12972561) and FYCO1 (By similarity). Interacts with the PIK3C3/VPS34-PIK3R4 complex (By similarity). The GTP-bound form interacts with OSBPL1A and RAC1 (By similarity). Interacts with CLN3 (By similarity). Interacts with CHM, the substrate-binding subunit of the Rab geranylgeranyltransferase complex (By similarity). Interacts with C9orf72 (PubMed:24549040). Does not interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4) (PubMed:20048159). Interacts with CLN5 (By similarity). Interacts with PLEKHM1 (via N- and C-terminus) (PubMed:27777970). Interacts with RUFY4 (By similarity). Interacts with PRPH; the interaction is direct (PubMed:23179371). Interacts with VPS13A (By similarity). The GDP-bound form interacts with RIMOC1 (By similarity). Interacts with the MON1A-CCZ1B complex and this interaction is enhanced in the presence of RIMOC1 (By similarity).|||Late endosome membrane|||Lipid droplet|||Lysosome membrane|||Melanosome membrane|||Mitochondrion membrane|||Reduces both the basal and, to a greater degree, agonist-stimulated glycerol releases. the ADRB2-stimulated liposlysis.|||Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transporter-mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism. Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes. Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and Mycobacteria. Plays a role in the fusion of phagosomes with lysosomes. Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses. Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA. Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation (By similarity). Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway (PubMed:23708524). Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). Required for vesicular trafficking and cell surface expression of ACE2 (By similarity). May play a role in PRPH neuronal intermediate filament assembly (PubMed:23179371).|||Widely expressed. High expression in liver, heart and kidney. Found in sensory and motor neurons.|||autophagosome membrane|||phagosome membrane http://togogenome.org/gene/10090:Nfkb1 ^@ http://purl.uniprot.org/uniprot/P25799 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Act as inhibitors of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm.|||By phorbol ester and TNF-alpha.|||Component of the NF-kappa-B p65-p50 complex (By similarity). Homodimer; component of the NF-kappa-B p50-p50 complex (By similarity). Component of the NF-kappa-B p105-p50 complex (By similarity). Component of the NF-kappa-B p50-c-Rel complex (By similarity). Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 (By similarity). Also interacts with MAP3K8 (By similarity). NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity (By similarity). Interacts with TSC22D3; this interaction prevents nuclear translocation and DNA-binding (By similarity). Interacts with SPAG9 and UNC5CL (By similarity). NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50 (By similarity). NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2 (By similarity). Interacts with GSK3B; the interaction prevents processing of p105 to p50 (By similarity). NFKB1/p50 interacts with NFKBIE (By similarity). NFKB1/p50 interacts with NFKBIZ (PubMed:11356851, PubMed:15241416). Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID (PubMed:11931770). Directly interacts with MEN1 (By similarity). Interacts with HIF1AN (By similarity). Interacts with FEM1AA; interaction is direct (PubMed:18270204).|||Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor. Together with RELA/p65, binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions.|||Cytoplasm|||Generation of the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) transcription factor takes place both cotranslationally and post-translationally via non-mutually exclusive mechanisms (By similarity). A cotranslational processing allows the production of both p50 and p105 (Nuclear factor NF-kappa-B p105 subunit) from a single NFKB1 mRNA (PubMed:9529257). While translation occurs, the particular unfolded structure after the GRR repeat region acts as a substrate for the proteasome, promoting degradation of the C-terminus (PubMed:9529257). The GRR acts as a proteasomal 'stop signal', protecting the region upstream of the GRR from degradation and promoting generation of p50 (PubMed:9529257). It is unclear if limited proteasome degradation during cotranslational processing depends on ubiquitination (PubMed:9529257). NF-kappa-B p50 is also generated post-translationally following ubiquitination by the KPC complex, leading to limited processing by the proteasome downstream of the GRR region, thereby generating p50 (By similarity).|||Glycine-rich region (GRR) is a critical element in the generation of p50 (Nuclear factor NF-kappa-B p50 subunit) by acting as a proteasomal 'stop signal', which leads to limited proteasomal degradation of the C-terminus, while generating p50.|||Isoform 3 (p98) (but not p84 or p105) acts as a transactivator of NF-kappa-B-regulated gene expression.|||NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. Plays a role in the regulation of apoptosis. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.|||Nucleus|||P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B. Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105.|||Phosphorylation at the C-terminus by IKBKB/IKKB acts as a signal for ubiquitination and promotes either complete degradation or processing to generate the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (By similarity). Phosphorylation at Ser-910 primes p105 for proteolytic processing in response to TNF-alpha stimulation (By similarity). Phosphorylation at Ser-926, Ser-930 and Ser-935 are required for BTRC/BTRCP-mediated ubiquitination and proteolysis (By similarity). Phosphorylation at Ser-930 is also required for ubiquitination by the KPC complex and limited processing to generate NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (By similarity).|||Polyubiquitinated at multiple Lys residues in the C-terminus (By similarity). Polyubiquitinated by the SCF(FBXW11) and SCF(BTRC) complexes following phosphorylation at Ser-926, Ser-930 and Ser-935, leading to its complete degradation (By similarity). In contrast, polyubiquitination by the KPC complex following phosphorylation at Ser-930 leads to limited proteosomal processing and generation of the active NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (By similarity).|||S-nitrosylation of Cys-59 affects DNA binding.|||The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription activation.|||The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation. http://togogenome.org/gene/10090:Il17f ^@ http://purl.uniprot.org/uniprot/Q7TNI7 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-17 family.|||Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:23255360, PubMed:18025225, PubMed:19144317). IL17A-IL17F signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:17911633, PubMed:15477493, PubMed:18025225). IL17A-IL17F is primarily involved in host defense against extracellular bacteria and fungi by inducing neutrophilic inflammation (PubMed:18025225, PubMed:23255360). As signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (PubMed:18025225). Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (PubMed:19144317). IL17F homodimer can signal via IL17RC homodimeric receptor complex, triggering downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:28813677). Via IL17RC induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi (PubMed:28813677). Likely via IL17RC, promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (PubMed:32076265). Regulates the composition of intestinal microbiota and immune tolerance by inducing antimicrobial proteins that specifically control the growth of commensal Firmicutes and Bacteroidetes (PubMed:29915298).|||Expressed by T-helper 17 cells (Th17) (at protein level). The expression pattern reflects the differentiation state. In fully differentiated Th17 cells, IL17A-IL17F heterodimers are produced at higher levels than IL17A-IL17A and IL17F-IL17F dimers (PubMed:18025225). Dominantly secreted in intestine (PubMed:29915298). Expressed by resident cells of the lamina propria, both epithelial cells and immune cell subsets including natural killer cells, dendritic cells, macrophages and various T and B cell subsets (PubMed:29915298, PubMed:16990136). Expressed by epithelial cells and innate immune cells in the colon (PubMed:19144317). Expressed in group 3 innate lymphoid cells (PubMed:23255360, PubMed:29915298).|||Homodimer; disulfide-linked (By similarity). Heterodimer with IL17A (IL17A-IL17F) (PubMed:18025225). Forms complexes with IL17RA and IL17RC receptors with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (By similarity). IL17F homodimer forms predominantly complexes with IL17RC homodimer, whereas IL17A-IL17F favors complexes with IL17RA-IL17RC (By similarity). IL17RA and IL17RC chains cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (By similarity).|||Induced upon antigen receptor binding in the presence of IL6 and TGB1 (PubMed:16990136, PubMed:18025225). Up-regulated by IL23A-IL12B, IL1B and TNF and inhibited by IFNG and IL4 in CD4-positive T cells (PubMed:18025225). Induced upon fungal infection in innate lymphoid cells (PubMed:23255360). Induced in lung epithelial cells upon bacterial and fungal infection (PubMed:28813677). Induced in brown adipose tissue upon cold exposure (PubMed:32076265).|||Mutant mice are born healthy at the expected Mendelian ratio, are fertile, and have no apparent phenotypic abnormalities (PubMed:19144317). They show increased susceptibility to S.aureus upper respiratory infection (PubMed:28813677). Mutant mice are protected from chemically induced colitis, a model of human inflammatory bowel disease (PubMed:29915298).|||Secreted http://togogenome.org/gene/10090:Vmn1r27 ^@ http://purl.uniprot.org/uniprot/K7N688 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd7 ^@ http://purl.uniprot.org/uniprot/P50283 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with SECTM1.|||Membrane|||Not yet known. http://togogenome.org/gene/10090:Mmp23 ^@ http://purl.uniprot.org/uniprot/O88676 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Endoplasmic reticulum membrane|||Expressed at relatively high level at 7 days old embryo compared to those at stadges day 11, 15 and 17.|||Expressed at relatively high level in heart, lung and spleen. Not detected in brain, liver, skeletal muscle, kidney and testis.|||Inhibited by TIMP2.|||Membrane|||N-glycosylated.|||Protease. May regulate the surface expression of some potassium channels by retaining them in the endoplasmic reticulum (By similarity).|||Proteolytic cleavage might yield an active form.|||The ShKT domain associates with, and blocks several potassium channels in the nanomolar to low micromolar range. The relative affinity is Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4 (By similarity). http://togogenome.org/gene/10090:Cpox ^@ http://purl.uniprot.org/uniprot/P36552 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-360 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the aerobic coproporphyrinogen-III oxidase family.|||Expressed in erythroid cells. Expressed in liver (PubMed:8407975).|||Homodimer.|||Involved in the heme biosynthesis. Catalyzes the aerobic oxidative decarboxylation of propionate groups of rings A and B of coproporphyrinogen-III to yield the vinyl groups in protoporphyrinogen-IX (By similarity).|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Fam76a ^@ http://purl.uniprot.org/uniprot/Q922G2 ^@ Similarity ^@ Belongs to the FAM76 family. http://togogenome.org/gene/10090:Trit1 ^@ http://purl.uniprot.org/uniprot/Q80UN9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IPP transferase family.|||Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37 of both cytosolic and mitochondrial tRNAs, leading to the formation of N6-(dimethylallyl)adenosine (i6A37) (PubMed:23289710). Mediates modification of a limited subset of tRNAs: tRNA(Ser)(AGA), tRNA(Ser)(CGA), tRNA(Ser)(UGA), as well as partial modification of the selenocysteine tRNA(Ser)(UCA) (By similarity). TRIT1 is therefore required for selenoprotein expression (PubMed:23289710).|||Cytoplasm|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Hyal1 ^@ http://purl.uniprot.org/uniprot/Q91ZJ9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 56 family.|||Detected in embryos of all developmental stages, with high level at the 7 day stage.|||Highly expressed in liver, kidney, lung and skin.|||Lysosome|||May have a role in promoting tumor progression. May block the TGFB1-enhanced cell growth.|||Secreted http://togogenome.org/gene/10090:Flrt2 ^@ http://purl.uniprot.org/uniprot/Q8BLU0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in adult brain (at protein level).|||Detected in embryonic brain at 13 dpc. Levels in brain decrease gradually after 15 dpc, but expression continues after birth (PubMed:21673655). Detected in embryonic myocardium, body wall and pro-epicardial organ at 9.5 dpc. Detected in the epicardial cell layer and throughout the myocardium at 10.5 dpc. Highly expressed in embryonic and neonate heart, but after that levels decrease strongly, and the protein is barely detectable 3 weeks after birth, with even lower levels after 7 and 15 weeks (at protein level) (PubMed:21350012). Detected in the anterior endoderm at 7.5 dpc. Detected on anterior somites, the allantois and mesenchymal tissue behind the developing heart at 8.5 dpc (PubMed:18448090). Detected in the cephalic mesenchyme and in tissue posterior to the developing heart at 9.5 and 10.5 dpc. Detected in the developing stomach and in a subset of the trunk sclerotome at 10.5 dpc. At 11 dpc, detected also in branchial arches, eyes and limbs (PubMed:16872596, PubMed:18448090).|||Endoplasmic reticulum membrane|||Functions in cell-cell adhesion, cell migration and axon guidance. Mediates cell-cell adhesion via its interactions with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:21350012, PubMed:25728924, PubMed:25374360). May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D (PubMed:21673655). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5D, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25728924). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis (PubMed:21350012).|||Heterozygous mice are viable and fertile, but homozygous mice display nearly complete embryonic lethality. Most embryos die at about 12.5 dpc, probably due to impaired expansion of the ventricular myocardium during development, reduced endocardial volume and heart insufficiency. Contrary to wild-type, the epicardium appears ruffled and presents numerous holes, due to defective formation of cell-cell adhesions. Still, there is a very small percentage of life-born pups that survive at least up to weaning.|||Microsome membrane|||N-glycosylated.|||Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.|||Secreted|||Self-associates (via leucine-rich repeats), giving rise to homooligomers (PubMed:25374360). Interacts with FGFR1 (PubMed:16872596). Interacts with FGFR2 (PubMed:21765038). Interacts (via extracellular domain) with ADGRL1/LPHN1 (PubMed:22405201). Interacts (via extracellular domain) with ADGRL3 (via olfactomedin-like domain)(PubMed:22405201, PubMed:25728924). Interacts (via extracellular domain) with UNC5D (via the first Ig-like domain) (PubMed:21673655, PubMed:25374360). Can also interact (via extracellular domain) with UNC5B, but with much lower affinity (PubMed:21673655). Interacts (via extracellular domain) with FN1 (PubMed:24585683).|||Up-regulated by FGF2.|||extracellular matrix|||focal adhesion|||synaptosome http://togogenome.org/gene/10090:Mup9 ^@ http://purl.uniprot.org/uniprot/A2CGB6|||http://purl.uniprot.org/uniprot/A9C496|||http://purl.uniprot.org/uniprot/P02762 ^@ Allergen|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in the urine of adult male mice but absent from that of females.|||Belongs to the calycin superfamily. Lipocalin family.|||Binds pheromones that are released from drying urine of males. These pheromones affect the sexual behavior of females.|||Causes an allergic reaction in human.|||Secreted|||There are about 15 group 1 MUP genes and their transcripts make up about 5% of male mouse liver RNA. http://togogenome.org/gene/10090:Usp14 ^@ http://purl.uniprot.org/uniprot/E9PYI8|||http://purl.uniprot.org/uniprot/Q9JMA1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. USP14/UBP6 subfamily.|||Cell membrane|||Cytoplasm|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Homodimer (Potential). Associates with the 26S proteasome. Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this interaction recruits USP14 to cleave ubiquitin chains of CGAS (By similarity).|||Homodimer (Potential). Associates with the 26S proteasome. Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this interaction recruits USP14 to cleave ubiquitin chains of CGAS.|||Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins (PubMed:16190881). Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1 (By similarity). Indispensable for synaptic development and function at neuromuscular junctions (NMJs) (PubMed:19726649). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation (By similarity). http://togogenome.org/gene/10090:Esf1 ^@ http://purl.uniprot.org/uniprot/A2APY6|||http://purl.uniprot.org/uniprot/Q3V1V3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ESF1 family.|||Interacts with ABT1. Forms a complex with ABT1 and suppresses the ABT1-induced activation of polymerase II-directed transcription in mammalian cells (By similarity).|||May constitute a novel regulatory system for basal transcription. Negatively regulates ABT1 (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Smoc1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1E4|||http://purl.uniprot.org/uniprot/E9QKW2|||http://purl.uniprot.org/uniprot/Q8BLY1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Found in the forebrain, midbrain, hindbrain, pharyngeal arch, somites, and forelimb buds at day 9.5 dpc. At day 10.5 dpc, strongly expressed in dorsal neural tube, developing pharyngeal arches and frontonasal region with low expression in the ectoderm overlying the developing optic vesicle, expression can be observed in the optic stalk. At 11.5 dpc it is localized to the closure site of the optic cup. In developing limbs between days 10.5 dpc and 11.5 dpc, it is found in both dorsal and ventral regions, but expression is predominant dorsal in hindlimb bud and not detected in the most anterior, posterior, and distal parts of limb buds. Expression coinciding with chondrogenic condensation can be observed at 12.5 dpc. Expression is restricted to future synovial joint regions at day 13.5 dpc.|||Glycosylated.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Null mice present with a phenotype resembling human microphthalmia with limb anomalies. The phenotype includes aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina is observed.|||Probable regulator of osteoblast differentiation. Plays essential roles in both eye and limb development.|||Widely expressed in many tissues with a strongest signal in ovary.|||basement membrane http://togogenome.org/gene/10090:Lsm11 ^@ http://purl.uniprot.org/uniprot/Q8BUV6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Component of the U7 snRNP complex that is involved in the histone 3'-end pre-mRNA processing (PubMed:12975319, PubMed:15824063). Increases U7 snRNA levels but not histone 3'-end pre-mRNA processing activity, when overexpressed (PubMed:12975319, PubMed:15824063). Required for cell cycle progression from G1 to S phases (PubMed:16914750). Binds specifically to the Sm-binding site of U7 snRNA.|||Component of the heptameric ring U7 snRNP complex, or U7 Sm protein core complex, at least composed of LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF, SNRPG and U7 snRNA (PubMed:12975319). Formation of the U7 snRNP is an ATP-dependent process mediated by a specialized SMN complex containing at least the Sm protein core complex and additionally, the U7-specific LSM10 and LSM11 proteins (PubMed:12975319). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (PubMed:19470752). Interacts (via the Sm domains) with CLNS1A (PubMed:16087681). Interacts with PRMT5, SMN, ZNF473 and WDR77 (PubMed:12975319, PubMed:16087681, PubMed:15824063).|||Not methylated.|||Nucleus|||The C-terminal SM 1 domain is both necessary for the binding to the Sm-binding site of U7 snRNA and U7 snRNP assembly (PubMed:12975319). The N-terminal domain is essential for histone pre-mRNA cleavage (PubMed:12975319). Amino acids 63-82 are sufficient to interact with ZNF473 (PubMed:12975319). http://togogenome.org/gene/10090:Mmp28 ^@ http://purl.uniprot.org/uniprot/Q8BG29|||http://purl.uniprot.org/uniprot/Q8CGV5|||http://purl.uniprot.org/uniprot/Q8CGV8 ^@ Cofactor|||Similarity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit. http://togogenome.org/gene/10090:Fmo5 ^@ http://purl.uniprot.org/uniprot/P97872|||http://purl.uniprot.org/uniprot/Q3TRA1 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as Baeyer-Villiger monooxygenase on a broad range of substrates. Catalyzes the insertion of an oxygen atom into a carbon-carbon bond adjacent to a carbonyl, which converts ketones to esters. Active on diverse carbonyl compounds, whereas soft nucleophiles are mostly non- or poorly reactive. In contrast with other forms of FMO it is non- or poorly active on 'classical' substrates such as drugs, pesticides, and dietary components containing soft nucleophilic heteroatoms. Able to oxidize drug molecules bearing a carbonyl group on an aliphatic chain, such as nabumetone and pentoxifylline. Also, in the absence of substrates, shows slow but yet significant NADPH oxidase activity (By similarity). Acts as a positive modulator of cholesterol biosynthesis as well as glucose homeostasis, promoting metabolic aging via pleiotropic effects (PubMed:26049045, PubMed:28646079).|||Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Expressed in liver (at protein level) (PubMed:26049045). Expressed in the mucosal epithelium of the gastrointestinal tract (PubMed:28646079).|||In the gastrointestinal tract, expression is induced in response to a high-fat diet.|||Membrane|||Microsome membrane|||Mutants exhibit a lean phenotype, which is age-related, becoming apparent after 20 weeks of age. Despite greater food intake, they weigh less, store less fat in white adipose tissue (WAT), have lower plasma glucose and cholesterol concentrations and enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure, with no increase in physical activity. They show a a higher rate of fatty acid oxidation in WAT (PubMed:26049045, PubMed:29686991). When fed a high-fat diet, they are protected against weight gain and reduction of insulin sensitivity (PubMed:28646079). http://togogenome.org/gene/10090:Col6a6 ^@ http://purl.uniprot.org/uniprot/Q8C6K9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type VI collagen family.|||Collagen VI acts as a cell-binding protein.|||In newborn, it is expressed in lung, heart, kidney, muscle, brain, intestine, skin, femur and sternum. In adult, it is expressed in lung, heart, muscle, ovary, brain, liver and sternum.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-4(VI) or alpha-5(VI) or alpha-6(VI).|||extracellular matrix http://togogenome.org/gene/10090:H2-M10.4 ^@ http://purl.uniprot.org/uniprot/Q85ZW8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Selenoi ^@ http://purl.uniprot.org/uniprot/Q80TA1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CDP-alcohol phosphatidyltransferase class-I family.|||Endoplasmic reticulum membrane|||Ethanolaminephosphotransferase that catalyzes the transfer of phosphoethanolamine/PE from CDP-ethanolamine to lipid acceptors, the final step in the synthesis of PE via the 'Kennedy' pathway. PE is the second most abundant phospholipid of membranes in mammals and is involved in various membrane-related cellular processes. The enzyme is critical for the synthesis of several PE species and could also catalyze the synthesis of ether-linked phospholipids like plasmanyl- and plasmenyl-PE which could explain it is required for proper myelination and neurodevelopment. http://togogenome.org/gene/10090:Vegfc ^@ http://purl.uniprot.org/uniprot/P97953 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDGF/VEGF growth factor family.|||Expressed in adult heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis and intestine with higher levels in heart, brain and kidney. Isoform 4 levels are very low. Isoform 3 is mostly expressed in liver and has reduced expression level in other tissues. Isoform 2 is mostly expressed in brain and kidney, although a lower level expression in other tissues is also detectable.|||Expression detected in mesenchymal cells of postimplantation embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions, and in the developing mesenterium. Also detected between vertebral corpuscles, in lung mesenchyme, in neck region and in developing forehead. Not detected in the blood islands of the yolk sac.|||Growth factor active in angiogenesis, and endothelial cell growth, stimulating their proliferation and migration and also has effects on the permeability of blood vessels. May function in angiogenesis of the venous and lymphatic vascular systems during embryogenesis, and also in the maintenance of differentiated lymphatic endothelium in adults. Binds and activates KDR/VEGFR2 and FLT4/VEGFR3 receptors.|||Homodimer; non-covalent and antiparallel (PubMed:9247316). Interacts with FLT4/VEGFR3; the interaction is required for FLT4/VEGFR3 homodimarization and activation (By similarity).|||Secreted|||Undergoes a complex proteolytic maturation which generates a variety of processed secreted forms with increased activity toward VEGFR-3, but only the fully processed form could activate VEGFR-2. VEGF-C first form an antiparallel homodimer linked by disulfide bonds. Before secretion, a cleavage occurs between Arg-223 and Ser-224 producing a heterotetramer. The next extracellular step of the processing removes the N-terminal propeptide. Finally the mature VEGF-C is composed mostly of two VEGF homology domains (VHDs) bound by non-covalent interactions (By similarity). http://togogenome.org/gene/10090:Fgf18 ^@ http://purl.uniprot.org/uniprot/A0A7U3JW51|||http://purl.uniprot.org/uniprot/O89101 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Interacts with FGFR3 and FGFR4.|||Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration. Required for normal ossification and bone development. Stimulates hepatic and intestinal proliferation (By similarity).|||Secreted http://togogenome.org/gene/10090:Skp1 ^@ http://purl.uniprot.org/uniprot/Q5SUR3|||http://purl.uniprot.org/uniprot/Q9WTX5 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the SKP1 family.|||Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit.|||Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1.|||Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2 (By similarity).|||Interacts with KDM2B, forming heterodimers (By similarity). The KDM2B-SKP1 heterodimeric complex interacts with the PCGF1-BCORL heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (By similarity). Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXw2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Component of the SCF(FBXW15) complex containing FBXW15 (PubMed:23319590). Interacts with CEP68 (By similarity). Interacts with FBXW15 (PubMed:23319590). Interacts with NOTCH2 (By similarity). The SKP1-KDM2A and SKP1-KDM2B complexes interact with UBB (By similarity).|||The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component.|||Undergoes autophagy-mediated degradation in the liver in a time-dependent manner. http://togogenome.org/gene/10090:Spatc1l ^@ http://purl.uniprot.org/uniprot/Q9D9W0 ^@ Similarity ^@ Belongs to the speriolin family. http://togogenome.org/gene/10090:Pbxip1 ^@ http://purl.uniprot.org/uniprot/Q3TVI8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Association to the cytoskeleton through a N-terminal leucine rich-domain (AA 190-218).|||Interacts with ESR1, PBX1, PBX2 and PBX3 (By similarity). Interacts with TEX11.|||Nucleus|||Regulator of pre-B-cell leukemia transcription factors (BPXs) function. Inhibits the binding of PBX1-HOX complex to DNA and blocks the transcriptional activity of E2A-PBX1. Tethers estrogen receptor-alpha (ESR1) to microtubules and allows them to influence estrogen receptors-alpha signaling (By similarity).|||The C-terminal domain (AA 443-731) contains a nuclear export signal.|||cytoskeleton http://togogenome.org/gene/10090:Preb ^@ http://purl.uniprot.org/uniprot/D3Z3S1|||http://purl.uniprot.org/uniprot/Q3UAP1|||http://purl.uniprot.org/uniprot/Q9WUQ2 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat SEC12 family.|||Detected starting at 10.5 dpc in the ectoderm and superficial mesoderm surrounding the caudal part of the tail region. At 12.5 dpc detected in dorsal root ganglia, surface ectoderm surrounding the caudal part of the tail, the inferior wall of the genital tubercle, developing liver, in Rathke pouch and in condensing mesenchyme forming the roof of the skull. At 14.5 dpc detected in the perichondrial region of the craniofacial, axial, and appendicular skeleton. By 16.5 dpc expression is much lower throughout the embryo, and is not detectable by 18.5 dpc.|||Endoplasmic reticulum membrane|||Guanine nucleotide exchange factor that specifically activates the small GTPase SAR1B. Mediates the recruitment of SAR1B and other COPII coat components to endoplasmic reticulum membranes and is therefore required for the formation of COPII transport vesicles from the ER.|||Interacts with SAR1B (GDP-bound form) (PubMed:11422940). Interacts with MIA2; recruits PREB to endoplasmic reticulum exit sites (By similarity). Interacts with CIDEB; facilitating loading of SCAP-SREBP into COPII vesicles (PubMed:30858281).|||Interacts with SAR1B (GDP-bound form). Interacts with MIA2; recruits PREB to endoplasmic reticulum exit sites.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Was first identified based on its probable role in the regulation of pituitary gene transcription. Binds to the prolactin gene (PRL) promoter and seems to activate transcription. http://togogenome.org/gene/10090:Or2d3b ^@ http://purl.uniprot.org/uniprot/A0A0R4J8U2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mpv17l ^@ http://purl.uniprot.org/uniprot/D3Z6M3|||http://purl.uniprot.org/uniprot/Q99MS3 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peroxisomal membrane protein PXMP2/4 family.|||By heat shock.|||Cytoplasm|||Isoform 1 and isoform 3 are expressed in the kidney (at protein level). Isoform 1 is expressed in the kidney, spleen, heart, brain, lung and liver. Isoform 3 is expressed in the kidney. Isoform 1 and isoform 3 expression increase during development, reache their highest level in adulthood and decrease with aging.|||Levels increase steadily between 1 week and 6 months after birth and decrease slightly between 6 months and 15 months after birth.|||Membrane|||Participates in reactive oxygen species metabolism by up- or down-regulation of the genes of antioxidant enzymes (PubMed:12471025, PubMed:15541722). Protective against the mitochondrial apoptotic cascade (By similarity).|||Participates in reactive oxygen species metabolism by up- or down-regulation of the genes of antioxidant enzymes.|||Peroxisome membrane http://togogenome.org/gene/10090:Glt8d1 ^@ http://purl.uniprot.org/uniprot/Q6NSU3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 8 family.|||Membrane http://togogenome.org/gene/10090:Ms4a1 ^@ http://purl.uniprot.org/uniprot/P19437|||http://purl.uniprot.org/uniprot/Q542S5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes. Functions as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR.|||Belongs to the MS4A family.|||Cell membrane|||Forms homotetramers. Interacts with the heavy and light chains of cell surface IgM, the antigen-binding components of the BCR.|||Mice have severely impaired T-cell independent antipolysaccharide antibody responses (PubMed:20038800). B-cell development is predominantly normal in CD20-deficient mice but calcium influx following CD19 or IgM ligation is reduced (PubMed:8450218).|||Phosphorylated. http://togogenome.org/gene/10090:Snrpa ^@ http://purl.uniprot.org/uniprot/Q62189 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM U1 A/B'' family.|||Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. U1 snRNP is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. SNRPA binds stem loop II of U1 snRNA. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. May bind preferentially to the 5'-UGCAC-3' motif on RNAs (By similarity).|||Nucleus|||U1 snRNP is composed of the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Interacts with SFPQ; component of a snRNP-free complex with SFPQ (By similarity). http://togogenome.org/gene/10090:Fadd ^@ http://purl.uniprot.org/uniprot/Q61160 ^@ Domain|||Function|||Subunit ^@ Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling.|||Can self-associate (By similarity). Interacts with CFLAR, PEA15 and MBD4 (By similarity). When phosphorylated, part of a complex containing HIPK3 and FAS (By similarity). May interact with MAVS/IPS1 (By similarity). Interacts with MOCV v-CFLAR protein and PIDD1 (By similarity). Interacts (via death domain) with FAS (via death domain) (By similarity). Interacts with CASP8 (PubMed:29440439). Interacts directly (via DED domain) with NOL3 (via CARD domain); inhibits death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (PubMed:15383280). Interacts with RIPK1, TRADD and CASP8 (PubMed:28842570, PubMed:29440439, PubMed:30185824, PubMed:31519887). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287). Interacts with stimulated TNFRSF10B (By similarity).|||Contains a death domain involved in the binding of the corresponding domain within Fas receptor.|||The interaction between the FAS and FADD death domains is crucial for the formation of the death-inducing signaling complex (DISC). http://togogenome.org/gene/10090:Ikbke ^@ http://purl.uniprot.org/uniprot/Q9R0T8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Lys-63'-linked polyubiquitinated at Lys-30 and Lys-403 by TRAF2:BIRC2 and TRAF2:BIRC3 complexes. Ubiquitination is induced by LPS, TNFA and interleukin-1 and required for full kinase activity and KF-kappa-B pathway activation (By similarity).|||Animals are hypersusceptible to influenza virus infection because of a defect in the activation of a subset of type 1 IFN-stimulated genes, however the amounts of IFNB produced are normals. Lungs of mice infected 7 days with influenza virus exhibit an inflammatory infiltrate consisting of lymphocytes, macrophages and neutrophils. After West Nile virus infection, animals display earlier neurological symptoms, a higher degree of neurovirulence and a failure to recover, compared to wild type. Animals are protected from high-fat diet-induced obesity, liver and adipose inflammation, hepatic steatosis and insulin resistance. They show an increased energy expenditure and thermogenesis and maintain insulin sensitivity in liver and adipose tissue.|||Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-503 upon IFN activation.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.|||Cytoplasm|||Expressed in bone marrow-derived macrophages and at low levels in liver and white adipose tissue (at protein level). Detected in muscle and lung.|||Homodimer (By similarity). Interacts with MAVS/IPS1 (By similarity). Interacts (via protein kinase domain) with TTLL12 (via N-terminus); the interaction prevents MAVS binding to IKBKE (By similarity). Interacts with the adapter proteins AZI2/NAP1, TANK and TBKBP1/SINTBAD (PubMed:17568778). Interacts with SIKE1 (By similarity). Interacts with TICAM1/TRIF, IRF3 and RIGI; interactions are disrupted by the interaction between IKBKE and SIKE1 (By similarity). Interacts with TOPORS; induced by DNA damage (By similarity). Interacts with CYLD, IKBKB, IKBKG and MYD88 (By similarity). Interacts with IFIH1 (By similarity). Interacts with DDX3X; the interaction may be induced upon virus infection (By similarity). Interacts with TRIM6 (via SPRY box) (By similarity). Interacts with unanchored K48-linked polyubiquitin chains; this leads to IKBKE activation (By similarity). Interacts with TBK1 (By similarity). Interacts with FKBP5 (By similarity).|||Induced by lipopolysaccharide (LPS) and TNFA. Under high-fat diet, highly induced (via NF-kappa-B) in adipocytes and M1-polarized adipose tissue macrophages.|||Kinase activity is inhibited competitively by amlexanox.|||Nucleus|||PML body|||Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.|||Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1 (By similarity). http://togogenome.org/gene/10090:G6pdx ^@ http://purl.uniprot.org/uniprot/Q00612|||http://purl.uniprot.org/uniprot/Q790Y8 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by ELP3 at Lys-403; acetylation inhibits its homodimerization and enzyme activity. Deacetylated by SIRT2 at Lys-403; deacetylation stimulates its enzyme activity (By similarity).|||Belongs to the glucose-6-phosphate dehydrogenase family.|||Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.|||Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis.|||Has NADP both as cofactor (bound to the N-terminal domain) and as structural element bound to the C-terminal domain.|||Homotetramer; dimer of dimers. Interacts with SIRT2; the interaction is enhanced by H(2)O(2) treatment (By similarity). Forms a ternary complex with ALDOB and TP53; this interaction is direct. ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check.|||Membrane|||cytosol http://togogenome.org/gene/10090:Eid1 ^@ http://purl.uniprot.org/uniprot/Q9DCR4 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in all adult tissues examined and during embryogenesis.|||Inhibition of MYOD1 may be partly due to the ability of EID1 to bind and inhibit EP300 histone acetyltransferase activity.|||Interacts via its LXCXE motif with the entire pocket region of RB1. Interacts with EP300, NR0B2 and TRIM27.|||Interacts with RB1 and EP300 and acts as a repressor of MYOD1 transactivation. Inhibits EP300 and CBP histone acetyltransferase activity. May be involved in coupling cell cycle exit to the transcriptional activation of genes required for cellular differentiation. May act as a candidate coinhibitory factor for NR0B2 that can be directly linked to transcription inhibitory mechanisms.|||Nucleus http://togogenome.org/gene/10090:Abca6 ^@ http://purl.uniprot.org/uniprot/Q8K441 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCA family.|||Expressed during embryogenesis.|||Golgi apparatus membrane|||Probable transporter which may play a role in macrophage lipid transport and homeostasis.|||Widely expressed with higher expression in heart, lung, brain, spleen and testis. http://togogenome.org/gene/10090:Or5t18 ^@ http://purl.uniprot.org/uniprot/A0A1L1STV1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tex44 ^@ http://purl.uniprot.org/uniprot/Q9DA60 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Foxn3 ^@ http://purl.uniprot.org/uniprot/Q499D0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional repressor. May be involved in DNA damage-inducible cell cycle arrests (checkpoints) (By similarity).|||Interacts through its C-terminus with the C-terminus of SNW1/SKIP.|||Nucleus http://togogenome.org/gene/10090:Prkacb ^@ http://purl.uniprot.org/uniprot/P68181 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Interacts with PRKAR1A and PRKAR2B (By similarity). The cAMP-dependent protein kinase catalytic subunit binds PJA2. Interacts with GPKOW.|||Activated by cAMP.|||Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.|||Cell membrane|||Cytoplasm|||Isoform 1 is found in all tissues examined, with the highest expression in the brain and very low levels in the testis. Isoform 2 is strongly expressed in the brain, in the prelimbic and insular cortex. Isoform 3 is also found only in the brain, but at very low levels.|||Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs (By similarity). PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux (PubMed:9368018). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (By similarity). Phosphorylates GPKOW which regulates its ability to bind RNA (By similarity). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (By similarity).|||Membrane|||Nucleus http://togogenome.org/gene/10090:Fhip1b ^@ http://purl.uniprot.org/uniprot/A0A1C7CYU5|||http://purl.uniprot.org/uniprot/Q3U2I3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the FHIP family.|||Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3. The FHF complex associates with the homotypic vesicular sorting complex (the HOPS complex).|||Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell. http://togogenome.org/gene/10090:Nf1 ^@ http://purl.uniprot.org/uniprot/Q04690 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds phospholipids via a region that includes the CRAL-TRIO domain. Binds primarily glycerophospholipids with monounsaturated C18:1 and/or C16:1 fatty acid moieties and a phosphatidylethanolamine or phosphatidylcholine headgroup. Has lesser affinity for lipids containing phosphatidylserine and phosphatidylinositol (By similarity).|||Cell membrane|||Expressed predominantly in adrenal gland, kidney, ovary and lung.|||Expressed predominantly in brain, spinal cord and testis.|||Interacts with HTR6. Interacts with SPRED2.|||Nucleus|||Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.|||Widely and more weakly expressed. Expressed mainly in testis.|||Widely and more weakly expressed. Predominantly expressed in adrenal gland.|||nucleolus http://togogenome.org/gene/10090:Adam28 ^@ http://purl.uniprot.org/uniprot/Q9JLN6 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||May play a role in organogenesis and organ-specific functions such as thymic T-cell development.|||Membrane|||Pro-domain removal and maturation may be, at least in part, autocatalytic.|||Strong expression in thymic epithelial cells and developmentally related tissues including the trachea, thyroid, lung and stomach, but not in lymphocytes. Expressed at high levels also in epididymis. In contrast with human is not expressed in immature or mature lymphocyte populations of thymocytes, lymph node, spleen, and bone marrow.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The expression patterns in adult and day 15.5 embryos are similar. http://togogenome.org/gene/10090:Gsc2 ^@ http://purl.uniprot.org/uniprot/A0A8Q0LQJ1|||http://purl.uniprot.org/uniprot/P56916 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Expressed in adult testis.|||Has a biphasic expression. Present in embryos in 8.5-10.5 dpc, reduced levels in 11.5 dpc and 13.5 dpc and absent in 15.5 dpc. Found in some adult tissues.|||May have a role in development. May regulate its own transcription. May bind the bicoid consensus sequence TAATCC.|||Nucleus http://togogenome.org/gene/10090:Or51d1 ^@ http://purl.uniprot.org/uniprot/E9Q550 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4f56 ^@ http://purl.uniprot.org/uniprot/A2AVW3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pop4 ^@ http://purl.uniprot.org/uniprot/Q9CR08 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic/archaeal RNase P protein component 1 family.|||Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.|||nucleolus http://togogenome.org/gene/10090:Otor ^@ http://purl.uniprot.org/uniprot/Q9JIE3 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MIA/OTOR family.|||Highly expressed in cochlea.|||Secreted http://togogenome.org/gene/10090:Emilin1 ^@ http://purl.uniprot.org/uniprot/Q99K41 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Detectable in morula and blastocyst. First expressed in ectoplacental cone in embryos of 6.5 days and in extraembryonic visceral endoderm at 7.5 days. Expressed also in the allantois. Expression in the ectoplacental cone-derived secondary trophoblast giant cells and spongiotrophoblast is strong up to 11.5 days and then declines. In the embryo, high levels are initially expressed in blood vessels, perineural mesenchyme and somites at 8.5 days. Later on, intense expression is identified in the mesenchymal component of organs anlage (ie lung and liver) and different mesenchymal condensations (ie limb bud and branchial arches). At late gestation expression is widely distributed in interstitial connective tissue and smooth muscle cell-rich tissues.|||Homotrimer associated through a moderately stable interaction of the C-terminal globular C1q domains, allowing the nucleation of the triple helix and then a further quaternary assembly to higher-order polymers via intermolecular disulfide bonds. Interacts with EMILIN2 (By similarity). Interacts with EFEMP2; this interaction promotes the incorporation of EFEMP2 into the extracellular matrix (PubMed:28717224).|||May be responsible for anchoring smooth muscle cells to elastic fibers, and may be involved not only in the formation of the elastic fiber, but also in the processes that regulate vessel assembly. Has cell adhesive capacity (By similarity). May have a function in placenta formation and initial organogenesis and a later role in interstitial connective tissue.|||extracellular matrix http://togogenome.org/gene/10090:Thap12 ^@ http://purl.uniprot.org/uniprot/Q9CUX1 ^@ Function|||Subunit ^@ Interacts with DNAJC3, probably sequestring it.|||Upstream regulator of interferon-induced serine/threonine protein kinase R (PKR). May block the PKR-inhibitory function of DNAJC3, resulting in restoration of kinase activity and suppression of cell growth. http://togogenome.org/gene/10090:Skint11 ^@ http://purl.uniprot.org/uniprot/A7XV14 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin and thymus.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Ift43 ^@ http://purl.uniprot.org/uniprot/Q9DA69 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis. Involved in retrograde ciliary transport along microtubules from the ciliary tip to the base.|||Belongs to the IFT43 family.|||Component of the IFT complex A (IFT-A) complex. IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B. Interacts directy with IFT122, WDR35 and TTC21B.|||Expressed in the retina, iris-ciliary body, lens and cornea. Higher expression is observed in the retina, predominantly in the photoreceptor outer segment.|||cilium|||cytoskeleton http://togogenome.org/gene/10090:Pgk1 ^@ http://purl.uniprot.org/uniprot/P09411 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphoglycerate kinase family.|||Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein). May play a role in sperm motility.|||Cytoplasm|||Monomer.|||Testis, lung, brain, skeletal muscle, liver, intestine, and kidney (at protein level). http://togogenome.org/gene/10090:Cdk1 ^@ http://purl.uniprot.org/uniprot/P11440 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Embryonic lethality in the first cell divisions.|||Follow a cyclic expression; during interphase, accumulates gradually following G1, S to reach a critical threshold at the end of G2, which promotes self-activation and triggers onset of mitosis. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis (Probable).|||Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Binds to RB1 and other transcription factors such as FOXO1 and RUNX2. Promotes G2-M transition when in complex with a cyclin-B. Interacts with DLGAP5. Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Isoform 2 is unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase. Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes. Interacts with FANCC. Interacts with CEP63; this interaction recruits CDK1 to centrosomes. Interacts with CENPA (By similarity). Interacts with NR1D1 (By similarity). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (PubMed:31437213).|||Mitochondrion|||Nucleus|||Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it.|||Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity. Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry. Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation. Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest (By similarity). In response to UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage checkpoint.|||Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (PubMed:16007079, PubMed:17700700, PubMed:17942597, PubMed:22405274). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS, ZAR1 and RUNX2 (PubMed:17942597, PubMed:22405274, PubMed:36264786). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (By similarity). Essential for early stages of embryonic development (By similarity). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:16007079, PubMed:17700700). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (By similarity). Phosphorylates KRT5 during prometaphase and metaphase (PubMed:29518391). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (By similarity). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (By similarity). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (By similarity). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (By similarity). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (By similarity). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (By similarity). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (By similarity). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (By similarity). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (By similarity). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (By similarity). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (By similarity). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (By similarity). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (By similarity). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (By similarity).|||Polyubiquitinated upon genotoxic stress.|||centrosome|||spindle http://togogenome.org/gene/10090:Nol3 ^@ http://purl.uniprot.org/uniprot/Q9D1X0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly (By similarity). Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation (By similarity). Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors (PubMed:16505176) (PubMed:24312627). Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis (By similarity). Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation (By similarity). Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner (By similarity). Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I (PubMed:24440909). Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (PubMed:22082675). Inhibits too myoblast differentiation through caspase inhibition (By similarity).|||CARD is critical for both extrinsic and intrinsic apoptotic pathways (By similarity). CARD domain mediates a protective effect against myocardial ischemia/reperfusion, oxidative stress and TNF-induced necrosis (PubMed:24440909). The C-terminal domain (amino acids 99 to 220) is involved in calcium binding and plays a protective role in calcium-mediated cell death (By similarity).|||Cytoplasm|||Membrane|||Mice homozygous for the NOL3-null allele are born normally and externally indistinguishable from littermates of other genotypes. NOL3-null mice grew to adulthood without any abnormalities in their general health and appearance under resting conditions. Under biomechanical stress, NOL3-deficient mice develop accelerated cardiomyopathy which is characterized by reduced contractile function, cardiac enlargement, and myocardial fibrosis. Likewise, under ischemia/reperfusion injury of NOL3-deficient mice have a markedly increased myocardial infarct sizes (PubMed:16505176). Double homozygous knockout mice for NOL3 and SGCD have an enhanced myofiber death and subsequent dystrophic disease (PubMed:24312627).|||Mitochondrion|||Oligomerizes (via CARD doamin) (By similarity). Interacts (via CARD domain) with CASP2; inhibits CASP2 activity in a phosphorylation-dependent manner (By similarity). Interacts with CASP8; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium. Interacts with TFPT; translocates NOL3 into the nucleus and negatively regulated TFPT-induced cell death (By similarity). Interacts directly (via CARD domain) with FAS and FADD (via DED domain); inhibits death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation. Interacts (via CARD domain) with BAX (via a C-terminal 33 residues); inhibits BAX activation and translocation and consequently cytochrome c release from mitochondria. Interacts with PPM1G; may dephosphorylate NOL3 (By similarity). Interacts (via CARD domain) with BBC3 (via BH3 domain); preventing the association of BBC3 with BCL2 and resulting in activation of CASP8 (By similarity). Interacts (via CARD domain) with BAD(via BH3 domain); preventing the association of BAD with BCL2 (By similarity). Interacts directly (via CARD domain) with TNFRSF1A; inhibits TNF-signaling pathway.|||Phosphorylation at Thr-149 is required for its antiapoptotic effect by blocking death-inducing signaling complex death-inducing signaling complex (DISC) activity through the control of interaction with CASP8. Phosphorylation at Thr-149 results in translocation to mitochondria and this translocation enables the binding to CASP8. Dephosphorylated at Thr-149 by calcineurin; doesn't inhibit the association between FADD and CASP8 and the consequent apoptosis.|||Polyubiquitinated by MDM2; promoting proteasomal-dependent degradation in response to apoptotic stimuli.|||Sarcoplasmic reticulum http://togogenome.org/gene/10090:Tmem128 ^@ http://purl.uniprot.org/uniprot/Q9CZB9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dnah17 ^@ http://purl.uniprot.org/uniprot/A2A520|||http://purl.uniprot.org/uniprot/E9Q7P0 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:St8sia4 ^@ http://purl.uniprot.org/uniprot/A0A087WRA0|||http://purl.uniprot.org/uniprot/Q53WR7|||http://purl.uniprot.org/uniprot/Q64692|||http://purl.uniprot.org/uniprot/Q6PAS1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Catalyzes the polycondensation of alpha-2,8-linked sialic acid required for the synthesis of polysialic acid (PSA), which is present on the embryonic neural cell adhesion molecule (N-CAM), necessary for plasticity of neural cells.|||Expressed throughout development at a low level.|||Golgi apparatus membrane|||Membrane|||Strongly expressed in lung, heart and spleen and weakly in brain. http://togogenome.org/gene/10090:Vmn2r47 ^@ http://purl.uniprot.org/uniprot/K7N709 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Bach2 ^@ http://purl.uniprot.org/uniprot/P97303 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. CNC subfamily.|||Cytoplasm|||Detected in brain and spleen.|||Homodimer; disulfide-linked (By similarity). Heterodimer of BACH2 and Maf-related transcription factors (PubMed:8887638).|||In brain, expression is lower in the adult than in the neonate.|||Nucleus|||Phosphorylation at Ser-520 downstream of the PI-3K pathway promotes nuclear export.|||The reversible disulfide bond may provide a mechanism to regulate the activity in oxidative stress responses.|||Transcriptional regulator that acts as repressor or activator (PubMed:8887638). Binds to Maf recognition elements (MARE) (PubMed:8887638). Plays an important role in coordinating transcription activation and repression by MAFK (PubMed:8887638). Induces apoptosis in response to oxidative stress through repression of the antiapoptotic factor HMOX1 (By similarity). Positively regulates the nuclear import of actin (PubMed:26021350). Is a key regulator of adaptive immunity, crucial for the maintenance of regulatory T-cell function and B-cell maturation (PubMed:28530713). http://togogenome.org/gene/10090:Fxyd2 ^@ http://purl.uniprot.org/uniprot/Q04646|||http://purl.uniprot.org/uniprot/Q6ITT1|||http://purl.uniprot.org/uniprot/Q6ITT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FXYD family.|||Highest levels expressed in the kidney and spleen. Restricted to the basolateral membrane in renal epithelial cells and varies in its level of expression along the nephron.|||May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.|||Membrane|||Regulatory subunit of the sodium/potassium-transporting ATPase which is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. http://togogenome.org/gene/10090:Nrl ^@ http://purl.uniprot.org/uniprot/P54846 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B. Functions also as a transcriptional coactivator, stimulating transcription mediated by the transcription factor CRX and NR2E3. Binds in a sequence-specific manner to the rhodopsin promoter.|||Belongs to the bZIP family.|||Cytoplasm|||Disumoylated at Lys-20. Sumoylation modulates the transcriptional activity of NRL on RHO and NR2E3 promoters, and is required for normal rod differentiation.|||Expressed in the retina (at protein level) (PubMed:11477108).|||Interacts with FIZ1; this interaction represses transactivation. Interacts (via the leucine-zipper domain) with CRX.|||Nucleus|||Phosphorylated.|||Photoreceptor precursors in retina produce only cones that primarily express S-opsin.|||The minimal transactivation domain (MTD) is conserved across the MAF family, it may activate transcription by recruiting TBP and associated factors at the promoters of target genes. http://togogenome.org/gene/10090:Ifitm2 ^@ http://purl.uniprot.org/uniprot/Q99J93 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||Cell membrane|||From 5.5 dpc to 7.5 dpc expressed within the epiblast. At 8.5 dpc expressed throughout the entire embryo. Expressed in the gonadal germ cells at 11.5 dpc/12.5.|||IFN-induced antiviral protein which inhibits the entry of viruses to the host cell cytoplasm, permitting endocytosis, but preventing subsequent viral fusion and release of viral contents into the cytosol. Active against multiple viruses, including influenza A virus, SARS coronavirus (SARS-CoV), Marburg virus (MARV) and Ebola virus (EBOV), Dengue virus (DNV) and West Nile virus (WNV). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry and SARS-CoV S protein-mediated viral entry. Induces cell cycle arrest and mediates apoptosis by caspase activation and in p53-independent manner.|||Interacts with CD81.|||Late endosome membrane|||Lysosome membrane|||Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity.|||Phosphorylation at Tyr-19 is required for endosomal and lysosomal location.|||Predominantly expressed in nascent primordial germ cells, as well as in gonadal germ cells. http://togogenome.org/gene/10090:Serpinc1 ^@ http://purl.uniprot.org/uniprot/P32261|||http://purl.uniprot.org/uniprot/Q543J5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the serpin family.|||Forms protease inhibiting heterodimer with TMPRSS7.|||Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin (By similarity).|||Phosphorylated by FAM20C in the extracellular medium.|||Plasma.|||extracellular space http://togogenome.org/gene/10090:Ildr2 ^@ http://purl.uniprot.org/uniprot/B5TVM2 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. LISCH7 family.|||Endoplasmic reticulum membrane|||Expressed in epithelial tissues, mainly in liver, kidney and colon.|||Interacts with MARVELD2 and OCLN (PubMed:23239027). Interacts with P4HB and HSPA5; the interaction with HSPA5 stabilizes ILDR2 expression (PubMed:33863978). Interacts (via C-terminus) with TRA2A, TRA2B and SRSF1 (PubMed:28785060).|||It is uncertain whether Met-1 or Met-16 is the initiator.|||May be involved in ER stress pathways with effects on lipid homeostasis and insulin secretion (PubMed:33863978, PubMed:23826244). With ILDR1 and LSR, involved in the maintain of the epithelial barrier function through the recruitment of MARVELD2/tricellulin to tricellular tight junctions (PubMed:23239027). Also functions as a B7-like protein family member expressed on immune cells and inflamed tissue and with T-cell inhibitory activity (PubMed:29431694). In the inner ear, may regulate alternative pre-mRNA splicing via binding to TRA2A, TRA2B and SRSF1 (PubMed:28785060).|||Nucleus|||Steatotic liver with increased hepatic and circulating triglycerides and total cholesterol. Shows reduced expression of genes mediating synthesis and oxidation of hepatic lipids.|||tight junction http://togogenome.org/gene/10090:Fads2 ^@ http://purl.uniprot.org/uniprot/Q9Z0R9 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family.|||Endoplasmic reticulum membrane|||Found in 13-day-old embryo heart.|||Highly expressed in the adrenal gland, liver, brain, and testis, tissues where lipogenesis and steroidogenesis are active. Also detected in lung, heart, and skeletal muscle.|||Induced by dietary PUFA-deficient diet. Induced by a fat-free diet and by a diet containing triolein (18:1n-9) as the only fat source. Down-regulated in liver by dietary PUFA.|||Involved in the biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively (PubMed:9867867). Subsequently, in the biosynthetic pathway of HUFA n-3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function (By similarity). It can also desaturate (11E)-octadecenoate (trans-vaccenoate) at carbon 6 generating (6Z,11E)-octadecadienoate (By similarity). In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates (By similarity).|||The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases. http://togogenome.org/gene/10090:Mchr1 ^@ http://purl.uniprot.org/uniprot/Q8JZL2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed predominantly in the brain. Expression in brain is negatively regulated by leptin. Also found in the epithelium of the tongue and kidney.|||Interacts with NCDN.|||Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis. http://togogenome.org/gene/10090:Zdhhc22 ^@ http://purl.uniprot.org/uniprot/A0PK84 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DHHC palmitoyltransferase family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with CNN3.|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes (By similarity). Catalyzes the palmitoylation of KCNMA1, regulating localization of KCNMA1 to the plasma membrane (By similarity). Might also mediate palmitoylation of CNN3 (Probable).|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Gbp10 ^@ http://purl.uniprot.org/uniprot/Q000W5 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. http://togogenome.org/gene/10090:Slc1a7 ^@ http://purl.uniprot.org/uniprot/Q8JZR4|||http://purl.uniprot.org/uniprot/Z4YKJ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.|||Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A7 subfamily.|||Expressed in retina, located in both cone and rod photoreceptor terminals and in axon terminals of rod bipolar cells.|||Interacts with the PDZ domains of DLG4.|||Membrane|||Photoreceptor inner segment membrane|||Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate. Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (By similarity). Acts primarily as an inhibitory glutamate-gated chloride channel being a major inhibitory presynaptic receptor at mammalian rod bipolar cell axon terminals. Glutamate binding gates a large Cl(-) conductance that mediates inhibition, affecting visual processing in the retina (PubMed:16973698, PubMed:32233906).|||Synaptic cell membrane http://togogenome.org/gene/10090:Or4c127 ^@ http://purl.uniprot.org/uniprot/Q8VGN2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dpf3 ^@ http://purl.uniprot.org/uniprot/P58269 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a regulator of myogenesis in cooperation with HDGFL2 (PubMed:32459350). Mediates the interaction of HDGFL2 with the BAF complex (PubMed:32459350). HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350).|||Belongs to the requiem/DPF family.|||Component of the BAF complex, which includes at least actin (ACTB), ARID1A, ARID1B/BAF250, SMARCA2, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3 (By similarity). Interacts with acetylated histones H3 and H4 (By similarity). Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523).|||Expressed in the heart and somites. Expressed in cerebellum and spinal cord, but not in cerebral cortex. Expressed specifically in post-mitotic neurons (at protein level).|||First expressed in the first differentiating cardiomyocytes of the cardiac crescent at 7.5 dpc and in the first somites at 8.0 dpc. In the heart, expression is restricted to the myocardial compartment. In the developing forebrain and cerebellar primordium, strictly expressed in post-mitotic neurons.|||Interacts with HDGFL2 (PubMed:32459350). Interacts with SMARCA4/BRG1/BAF190A, SMARCC1/BAF155 and SMARCD1/BAF60A (By similarity).|||Muscle-specific component of the BAF complex, a multiprotein complex involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Specifically binds acetylated lysines on histone 3 and 4 (H3K14ac, H3K9ac, H4K5ac, H4K8ac, H4K12ac, H4K16ac). In the complex, it acts as a tissue-specific anchor between histone acetylations and methylations and chromatin remodeling. It thereby probably plays an essential role in heart and skeletal muscle development (By similarity). Belongs to the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.|||Nucleus|||The PHD-type zinc fingers mediate the binding to acetylated histones. http://togogenome.org/gene/10090:Or4a72 ^@ http://purl.uniprot.org/uniprot/A0A1L1SQJ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trpm8 ^@ http://purl.uniprot.org/uniprot/Q8R4D5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM8 sub-subfamily.|||Cell membrane|||Expressed in dorsal root and trigeminal ganglia. Specifically expressed in a subset of pain- and temperature-sensing neurons. Not expressed in heavily myelinated neurons. Not expressed in neurons expressing TRPA1 or TRPV1.|||Interacts (via N-terminus and C-terminus domains) with TCAF1; the interaction stimulates TRPM8 channel activity. Interacts (via N-terminus and C-terminus domains) with TCAF2; the interaction inhibits TRPM8 channel activity (By similarity). Homotetramer.|||Membrane raft|||N-glycosylation is not essential for but facilitates cell surface expression, multimerization, association with lipid rafts and ion channel activity.|||Receptor-activated non-selective cation channel involved in detection of sensations such as coolness, by being activated by cold temperature below 25 degrees Celsius. Activated by icilin, eucalyptol, menthol, cold and modulation of intracellular pH. Involved in menthol sensation. Permeable for monovalent cations sodium, potassium, and cesium and divalent cation calcium. Temperature sensing is tightly linked to voltage-dependent gating. Activated upon depolarization, changes in temperature resulting in graded shifts of its voltage-dependent activation curves. The chemical agonists menthol functions as a gating modifier, shifting activation curves towards physiological membrane potentials. Temperature sensitivity arises from a tenfold difference in the activation energies associated with voltage-dependent opening and closing.|||The coiled coil region is required for multimerization. http://togogenome.org/gene/10090:Obscn ^@ http://purl.uniprot.org/uniprot/E9QQ96|||http://purl.uniprot.org/uniprot/H7BX05 ^@ Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Srprb ^@ http://purl.uniprot.org/uniprot/P47758 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SRP receptor beta subunit family.|||Component of the SRP (signal recognition particle) receptor (PubMed:7844142). Ensures, in conjunction with the signal recognition particle, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (PubMed:7844142). May mediate the membrane association of SR (PubMed:7844142).|||Endoplasmic reticulum membrane|||Heterodimer with SRPRA. http://togogenome.org/gene/10090:AI837181 ^@ http://purl.uniprot.org/uniprot/Q8VD62 ^@ Similarity ^@ Belongs to the UPF0696 family. http://togogenome.org/gene/10090:Akr7a5 ^@ http://purl.uniprot.org/uniprot/Q8CG76 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldo/keto reductase family. Aldo/keto reductase 2 subfamily.|||Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen (By similarity).|||Cytoplasm|||Expressed in liver, kidney, testis and brain with low levels in skeletal muscle, spleen, heart and lung.|||Golgi apparatus|||Homodimer.|||Inhibited by citrate, succinate and tartrate.|||Mitochondrion http://togogenome.org/gene/10090:Ripply3 ^@ http://purl.uniprot.org/uniprot/Q924S9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional corepressor. Negative regulator of the transcriptional activity of TBX1. Plays a role in the development of the pharyngeal apparatus and derivatives.|||Belongs to the ripply family.|||Expressed in the endoderm and ectoderm cells of the caudal pharyngeal region at 8.5 dpc.|||Interacts with TBX1.|||Mice are viable, fertile and morphologically normal. Show abnormal development of pharyngeal derivatives, including ectopic formation of the thymus and the parathyroid gland, as well as cardiovascular malformation.|||Nucleus|||The Ripply homology domain and the WRPW motif are both necessary for its transcriptional corepressor activity on the transcription activator TBX1.|||The WRPW motif is required for binding to tle/groucho proteins. http://togogenome.org/gene/10090:Dipk1c ^@ http://purl.uniprot.org/uniprot/Q8BQT2 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Among the many cysteines in the lumenal domain, most are probably involved in disulfide bonds.|||Belongs to the DIPK family.|||Endoplasmic reticulum membrane|||Mainly expressed in the brain and eye, some expression in kidney and skeletal muscle. http://togogenome.org/gene/10090:Cux2 ^@ http://purl.uniprot.org/uniprot/P70298 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CUT homeobox family.|||Knockout mice show moderately but consistently bigger brains than wild-type animals. Cell density and thickness of upper cortical layers (II-IV) are increased, while there are no differences in neuronal density in layers V and VI (PubMed:18033766). Neurons in layer II-III show simpler morphologies, with a significant decrease in the dendritic length and the number of branches, as well as a severe reduction of dendritic spines density associated with synaptic defects. The working memory is impaired (PubMed:20510857).|||Nucleus|||Restricted to neural tissues. Expressed exclusively in the central and peripheral nervous systems.|||Transcription factor involved in the control of neuronal proliferation and differentiation in the brain (PubMed:18033766, PubMed:20510857). Regulates dendrite development and branching, dendritic spine formation, and synaptogenesis in cortical layers II-III (PubMed:20510857). Binds to DNA in a sequence-specific manner. http://togogenome.org/gene/10090:Rap1gds1 ^@ http://purl.uniprot.org/uniprot/E9Q912 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a GEF (guanine nucleotide exchange factor) for prenylated RHOA. Acts as a GEF for RHOC. Chaperones the downstream trafficking and/or processing of small newly prenylated GTPases. Escorts RAC1 to the nucleus.|||Acts as a GEF (guanine nucleotide exchange factor) for the Rho family of small GTP-binding proteins (G proteins) that stimulates the dissociation of GDP to enable subsequent binding of GTP. Additionally, appears to chaperone the processing and/or trafficking of small GTPases containing a C-terminal polybasic region independently of GEF activity. Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1 and KRAS. Regulates mitochondrial dynamics by controlling RHOT function to promote mitochondrial fission during high calcium conditions. Able to promote the Ca(2+) release from the endoplasmic reticulum via both inositol trisphosphate (Ins3P) and ryanodine sensitive receptors leading to a enhanced mitochondrial Ca(2+) uptake.|||Acts as a GEF (guanine nucleotide exchange factor) for unprenylated RHOA. Chaperones the entry and passage of small GTPases through the prenylation pathway. Recognizes the last amino acid in the GTPase C-terminal CAAX motif with a preference for 'Leu' over 'Met', indicating involvement in the geranylgeranylation pathway. May also recognize prenylated GTPases.|||Endoplasmic reticulum|||Interacts with RABL3. Interacts with RHOT1.|||Interacts with prenylated RHOA; the interaction is direct and in a 1:1 stoichiometry. Interacts with RAP1A. Interacts with KRAS. Interacts with RAC1. Interacts with RAP1B. Preferentially interacts with prenylated GTPases.|||Interacts with unprenylated RHOA; the interaction is direct. Interacts with RAP1A. Interacts with KRAS. Interacts with RAC1. Interacts with RAP1B. Preferentially interacts with unprenylated GTPases that will become geranylgeranylated. May also interact with prenylated GTPases.|||Mitochondrion|||Nucleus|||Serotonylated on Gln residues by TGM2 in response to hypoxia, leading to its inactivation.|||cytosol http://togogenome.org/gene/10090:Sptlc1 ^@ http://purl.uniprot.org/uniprot/O35704 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.|||Component of the serine palmitoyltransferase (SPT) complex, which is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB (By similarity). The heterodimer with SPTLC2 or SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity (By similarity). SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides (By similarity). Forms dimers of heterodimers with SPTLC2 (By similarity). Interacts with RTN4 (isoform B) (PubMed:26301690).|||Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases (PubMed:28100772). The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (By similarity). Required for adipocyte cell viability and metabolic homeostasis (PubMed:28100772).|||Endoplasmic reticulum membrane|||Expressed in a variety of tissues. Highest expression in brain, kidney and liver (PubMed:21994399). Expressed in brown and white adipose tissues (PubMed:27818258).|||Expression levels at protein level increase upon high-fat diet. mRNA levels remain unchanged.|||Highly expressed after birth, expression decreases 2 weeks after birth and is maintained until, at least, 18 months.|||Knockout are lethal at embryonic stage (PubMed:28100772). Conditional knockouts specific to the adipose tissue develop adipose tissue but exhibit a striking age dependent loss of adipose tissue accompanied by evidence of adipocyte death, increased macrophage infiltration and tissue fibrosis. They also have elevated fasting blood glucose, fatty liver and insulin resistance. They show a significant reduction of total sphingomyelin levels in the adipose tissue (PubMed:28100772).|||Phosphorylation at Tyr-164 inhibits activity and promotes cell survival.|||SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides (By similarity). This mechanism allows to maintain ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (Probable).|||The transmembrane domain is involved in the interaction with ORMDL3. http://togogenome.org/gene/10090:Alox15 ^@ http://purl.uniprot.org/uniprot/A2CF88|||http://purl.uniprot.org/uniprot/P39654 ^@ Caution|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||Cell membrane|||Found in pituitary and pineal glands as well as leukocytes, kidney, aorta, small intestine and cornea (PubMed:15708862, PubMed:22503541, PubMed:8188678). Also expressed by resident peritoneal macrophages (at protein level) (PubMed:8798642).|||Interacts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lipid droplet|||Mice are fertile and do not display overt phenotype. However, reduced endoplasmic reticulum stress response to high-fat diet is observed. Aged mice also display systemic autoimmunity, a significant and spontaneous production of several forms of autoantibodies being detected and glomerulonephritis and deposits of complement and immunoglobulins within their glomeruli being observed. They also display reduced bone mass.|||Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators (PubMed:8188678). It inserts peroxyl groups at C12 or C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-hydroperoxyeicosatetraenoate/12-HPETE and 15-hydroperoxyeicosatetraenoate/15-HPETE (PubMed:8188678). It may then act on 12-HPETE to produce hepoxilins, which may show pro-inflammatory properties (By similarity). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate. May participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets. Can convert epoxy fatty acids to hydroperoxy-epoxides derivatives followed by an intramolecular nucleophilic substitution leading to the formation of monocyclic endoperoxides (By similarity). Plays an important role during the maintenance of self-tolerance by peroxidizing membrane-bound phosphatidylethanolamine which can then signal the sorting process for clearance of apoptotic cells during inflammation and prevent an autoimmune response (PubMed:22503541). In addition to its role in the immune and inflammatory responses, this enzyme may play a role in epithelial wound healing in the cornea through production of lipoxin A4 (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1; 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory and neuroprotective properties (PubMed:15708862). Furthermore, it may regulate actin polymerization which is crucial for several biological processes such as the phagocytosis of apoptotic cells (PubMed:11278875). It is also implicated in the generation of endogenous ligands for peroxisome proliferator activated receptor (PPAR-gamma), hence modulating macrophage development and function (PubMed:10432118). It may also exert a negative effect on skeletal development by regulating bone mass through this pathway (PubMed:14716014). As well as participates in ER stress and downstream inflammation in adipocytes, pancreatic islets, and liver (PubMed:22215650). Finally, it is also involved in the cellular response to IL13/interleukin-13 (By similarity).|||The PLAT domain can bind calcium ions; this promotes association with membranes.|||Up-regulated in response to endoplasmic reticulum stress (at protein level).|||cytosol http://togogenome.org/gene/10090:Camta2 ^@ http://purl.uniprot.org/uniprot/B0QZH4|||http://purl.uniprot.org/uniprot/B0QZH6|||http://purl.uniprot.org/uniprot/Q80Y50 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAMTA family.|||May interact with calmodulin.|||Nucleus|||Transcription activator. May act as tumor suppressor (By similarity). http://togogenome.org/gene/10090:Krt15 ^@ http://purl.uniprot.org/uniprot/B1AQ77|||http://purl.uniprot.org/uniprot/Q61414 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||During wound healing expression is suppressed by TGF-beta, TNF-alpha and to a lesser extent by epidermal and keratinocyte growth factors (EGF and KGF respectively).|||Expressed in the skin at birth (at protein level) (PubMed:11408584). In neonatal mice, additional expression seen in the basal layer of the cornea, forestomach and esophagus (at protein level).|||Expressed strongly in the basal cell layer at the tips of rete-like prominences (RLPs) of adult dorsal tongue, outer root sheath (ORS) of hair follicle and skin epidermis (at protein level).|||Heterotetramer of two type I and two type II keratins (Probable). Forms a heterodimer with KRT14 (PubMed:24940650). Interacts with PLEC isoform 1C, when in a heterodimer with KRT14 (PubMed:24940650). Interacts with NOD2 (By similarity).|||In the absence of KRT14, makes a bona fide, but ultrastructurally distinct keratin filament network with KRT5.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Car3 ^@ http://purl.uniprot.org/uniprot/P16015 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-carbonic anhydrase family.|||Cytoplasm|||Expressed at lower levels in adipose tissue from animals that were either genetically obese or had experimentally induced obesity.|||Inhibited by acetazolamide.|||Reversible hydration of carbon dioxide.|||S-glutathionylated in hepatocytes under oxidative stress.|||S-thiolated both by thiol-disulfide exchange with glutathione disulfide and by oxyradical-initiated S-thiolation with reduced glutathione. http://togogenome.org/gene/10090:Tmem140 ^@ http://purl.uniprot.org/uniprot/Q8BGY5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rad54l2 ^@ http://purl.uniprot.org/uniprot/E9QKL0|||http://purl.uniprot.org/uniprot/Q99NG0 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||DNA helicase that modulates androgen receptor (AR)-dependent transactivation in a promoter-dependent manner. Not able to remodel mononucleosomes in vitro. Acts as an AR-coregulator in Sertoli cells.|||Death by 11.5 dpc. At 9.5 dpc and 10.5 dpc, almost all major tissues are proportionally smaller, and the neural tube is shrunk in some embryos. Dramatically reduced cell proliferation and increased apoptosis are observed in 9.5 dpc and 10.5 dpc embryos. Embryonic fibroblasts stop to grow after 2 or 3 passages and exhibit increased apoptosis and decreased DNA synthesis compared with wild-type.|||Enzyme activity is enhanced by dsDNA (double-stranded DNA) and ssDNA (single-stranded DNA).|||Expressed at relatively low level, with highest expression in testis, liver and kidney. In brain, it is expressed in hippocampal and cerebellar neurons. In testis, it is present at high level in Sertoli cell nuclei. Also present in Leydig cell (at protein level).|||Interacts with AR via its N-terminus. Interacts with DYRK1A. Binds DNA and mononucleosomes, but does not seem to form large multiprotein complexes.|||Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to be important for the association with nuclear receptors.|||Mainly expressed in the neural tube and limb buds during early embryonic development. Also present in testis: at the onset of spermatogenesis, it is expressed in spermatogonia, pachytene, and diplotene spermatocytes. In Sertoli cells it is expressed in a stage-dependent manner, with high expression levels at stages II-VI and VII-VIII.|||Nucleus|||Sumoylated. http://togogenome.org/gene/10090:Card9 ^@ http://purl.uniprot.org/uniprot/A2AIV8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (PubMed:16862125, PubMed:20538615, PubMed:26679537, PubMed:29080677). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (PubMed:16862125, PubMed:20538615, PubMed:24470469, PubMed:25621893, PubMed:26679537, PubMed:29080677, PubMed:32548948). Transduces signals in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated molecular pattern metabolites (PAMPs), such as fungal carbohydrates, and trigger CARD9 activation (PubMed:16862125, PubMed:20538615). Upon activation, CARD9 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:16862125, PubMed:20538615, PubMed:22265677, PubMed:29080677). CARD9 signaling in antigen-presenting cells links innate sensing of fungi to the activation of adaptive immunity and provides a cytokine milieu that induces the development and subsequent of interleukin 17-producing T helper (Th17) cells (PubMed:17450144, PubMed:24470469, PubMed:32358020). Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (PubMed:17486093). CARD9 can also be engaged independently of BCL10: forms a complex with RASGRF1 downstream of C-type lectin receptors, which recruits and activates HRAS, leading to ERK activation and the production of cytokines (PubMed:25267792). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (PubMed:27158904, PubMed:33548172). Plays an essential role in antifungal immunity against dissemination of gut fungi: acts by promoting induction of antifungal IgG antibodies response in CX3CR1(+) macrophages to confer protection against disseminated C.albicans or C.auris infection (PubMed:33548172). Also mediates immunity against other pathogens, such as certain bacteria, viruses and parasites; CARD9 signaling is however redundant with other innate immune responses (PubMed:17187069, PubMed:26679537, PubMed:29080677). In response to L.monocytogenes infection, required for the production of inflammatory cytokines activated by intracellular peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B (PubMed:17187069).|||Cytoplasm|||Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (By similarity). Activation downstream of C-type lectin receptors, by phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers disruption of the CARD domain-coiled coil interface, CARD9 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:22265677). Zinc-binding inhibits activation by stabilizing the CARD ground-state conformation and restricting its capacity to form BCL10-nucleating filaments (By similarity).|||Mice were born at the normal Mendelian ratio without obvious anatomical defects but display impaired innate immunity (PubMed:16862125, PubMed:17187069). In response to C.albicans infection, mice develop fungal infections, many of which target the central nervous system (CNS) (PubMed:26679537). All mice die within 5 days after infection by C.albicans whereas more than half of the control mice survive for more than 12 days (PubMed:16862125). Impaired zymosan-induced cytokine production (PubMed:16862125). No defects in adaptive immunity (PubMed:16862125). Mice show impaired recruitment of neutrophils in CNS after infection by C.albicans, an immune cell critical for antifungal host defense (PubMed:26679537). Mice are susceptible to pulmonary infection with C.neoformans and show decreased Th17-related immune response (PubMed:24470469). Mice are highly susceptible to phaeohyphomycosis following E.spinifera infection and show impaired antifungal immunity, characterized by reduced cytokine production and neutrophil recruitment (PubMed:29080677). Mice are susceptible to A.fumigatus and P.pneumonia infection (PubMed:25621893, PubMed:32548948). Mice are more susceptible to colitis and have an increased load of gut-resident fungi (mycobiota), causing gut fungal dysbiosis (PubMed:23732773, PubMed:27158904). Mice are unable to induce an efficient IgG antibody response against disseminated C.albicans infection (PubMed:33548172). Following infection by L.monocytogenes, mice fail to clear infection and show altered cytokine production (PubMed:17187069).|||Monomer (By similarity). Homodimer; homodimerization is mediated by the CARD domain which forms an extensive interaction with the adjacent linker and coiled-coil regions; leads to an autoinhibited state (By similarity). Homomultimer; polymerizes following activation, forming a nucleating helical template that seeds BCL10-filament formation via a CARD-CARD interaction (By similarity). Interacts (via CARD domain) with BCL10 (via CARD domain); interaction takes place following CARD9 activation and polymerization, leading to the formation of a filamentous CBM complex assembly (PubMed:22265677). Component of a CBM complex (CARD9-BCL10, MALT1), composed of CARD9, BCL10 and MALT1 (PubMed:22265677). Interacts with RASGRF1 (By similarity). Interacts with NOD2 (via NACHT domain); interaction is direct (PubMed:17187069, PubMed:24960071). Interacts with RIPK2 (PubMed:17187069). Interacts with VHL; without leading to protein degradation (By similarity).|||Phosphorylated at Thr-231 by PRKCD downstream of C-type lectin receptors activation: phosphorylation promotes interaction with BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:22265677). Phosphorylated at Thr-531 and Thr-531 by CK2 following interaction with VHL, leading to inhibit the ability to activate NF-kappa-B (By similarity).|||Specifically expressed in myeloid cells (PubMed:16862125, PubMed:17187069). Not expressed in non-lymphoid organs (PubMed:16862125, PubMed:17187069).|||The linker region, also named autoinhibitory interface, is required to prevent constitutive activation and maintain CARD9 in an autoinhibitory state. Disruption of this region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments.|||Ubiquitinated at Lys-125 via 'Lys-27'-linked ubiquitin by TRIM62 downstream of C-type lectin receptors activation; leading to CARD9 activation, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Deubiquitinated at Lys-125 by USP15, inhibiting CARD9 (By similarity). http://togogenome.org/gene/10090:Txndc12 ^@ http://purl.uniprot.org/uniprot/Q9CQU0 ^@ Function|||Subcellular Location Annotation ^@ Endoplasmic reticulum lumen|||Protein-disulfide reductase of the endoplasmic reticulum that promotes disulfide bond formation in client proteins through its thiol-disulfide oxidase activity. http://togogenome.org/gene/10090:Nudt17 ^@ http://purl.uniprot.org/uniprot/Q9CWD3 ^@ Function|||Similarity ^@ Belongs to the Nudix hydrolase family.|||Probably mediates the hydrolysis of some nucleoside diphosphate derivatives. http://togogenome.org/gene/10090:Astl ^@ http://purl.uniprot.org/uniprot/Q6HA09 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Absence of cortical granules exocytosis during post-fertilization. Multiple capacitated sperm binding to eggs and two-cell embryos are not prevented. Post-fertilization cleavage of ZP2 does not occur.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Cortical granule|||Cytoplasm|||Expressed in embryonic stem cells.|||Inhibited by wide spectrum metalloproteinase inhibitor batimastat (BB-94). Also inhibited by EDTA (By similarity).|||Interacts (via N-terminal domain) with SPACA3; the interaction occurs during fertilization.|||Oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization. Plays a role in the polyspermy inhibition. Probably acts as a protease for the post-fertilization cleavage of ZP2. Cleaves the sperm-binding ZP2 at the surface of the zona pellucida after fertilization and cortical granule exocytosis, rendering the zona pellucida unable to support further sperm binding.|||Ovary-specific. Expressed in secondary, antral and Graafian follicle oocytes. Expressed in the egg cells. Not detected in two-cell embryos. Not detected in naked oocytes, oocytes in primordial or unilaminar primary follicles, or in any other ovarian cells at pre-pubertal, pubertal or adult stages (at protein level). Ovary-specific. http://togogenome.org/gene/10090:Adamts20 ^@ http://purl.uniprot.org/uniprot/P59511 ^@ Cofactor|||Disease Annotation|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Defects in Adamts20 are the cause of the belted (bt) phenotype. It is a pigmental defect which occurs as a result of a defect in melanocyte development.|||Expressed at low level in testis and brain.|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||May play a role in tissue-remodeling process occurring in both normal and pathological conditions. May have a protease-independent function in the transport from the endoplasmic reticulum to the Golgi apparatus of secretory cargos, mediated by the GON domain.|||The precursor is cleaved by a furin endopeptidase.|||extracellular matrix http://togogenome.org/gene/10090:Odf3l2 ^@ http://purl.uniprot.org/uniprot/Q3TZ65 ^@ Similarity ^@ Belongs to the CIMAP family. http://togogenome.org/gene/10090:Vmn1r192 ^@ http://purl.uniprot.org/uniprot/Q8K4C9 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Slc39a10 ^@ http://purl.uniprot.org/uniprot/Q6P5F6 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Expressed in the liver, kidney and brain.|||Greatly increased in liver and brain, in response to Zn(2+) deficiency (at protein level).|||Interacts with SLC39A6 (PubMed:27274087). This interaction triggers cells to undergo EMT and mitosis (By similarity). Found in a complex with SLC39A6, SLC39A10 and with the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (By similarity). Found in a complex with SLC39A6, SLC39A10 and with NCAM1; this complex controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-tomesenchymal transition (PubMed:28098160). Found in a complex with SLC39A6, SLC39A10 and with GSK3B that controls NCAM1 phosphorylation (PubMed:28098160).|||Undergoes N-terminal ectodomain shedding.|||Zinc-influx transporter. When associated with SLC39A6, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT). mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT). SLC39A10-SLC39A6 heterodimers play also an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (By similarity). Plays an important for both mature B-cell maintenance and humoral immune responses (PubMed:25074919). When associated with SLC39A10, the heterodimer controls NCAM1 phosphorylation and integration into focal adhesion complexes during EMT (PubMed:28098160). http://togogenome.org/gene/10090:Rab5if ^@ http://purl.uniprot.org/uniprot/Q9CQT9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EMC6 family.|||Component of the GET- and EMC-like (GEL) complex, composed of RAB5IF/OPTI and TMCO1 (By similarity). The GEL complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47) (By similarity). The MPT complex associates with the SEC61 complex (By similarity). Interacts with NDUFS3, NDUFA4, NDUFV1, NDUFA9 and NDUFS8 of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:31536960). Interacts with UQCRC2 of the ubiquinol-cytochrome c reductase complex (Complex III) (PubMed:31536960). Interacts with COX5A and COX7C of the cytochrome c oxidase complex (Complex IV) (PubMed:31536960).|||Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (By similarity). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity). Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (By similarity). In addition to its role in multi-pass membrane insertion, RAB5IF/OPTI also acts as an assembly factor for mitochondrial respiratory complexes (PubMed:31536960).|||Endoplasmic reticulum membrane|||Expressed in neuronal cells.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Unc50 ^@ http://purl.uniprot.org/uniprot/Q9CQ61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the unc-50 family.|||Golgi apparatus membrane|||Highly expressed in periodontal ligament and bone marrow, but not in gingival fibroblasts.|||Involved in the cell surface expression of neuronal nicotinic receptors (By similarity). Binds RNA (By similarity).|||Nucleus inner membrane http://togogenome.org/gene/10090:Nxf1 ^@ http://purl.uniprot.org/uniprot/Q99JX7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NXF family.|||Cytoplasm|||Expressed ubiquitously.|||Heterodimer (via NTF2 domain) with NXT1 (By similarity). The formation of NXF1-NXT1 heterodimers is required for the NXF1-mediated nuclear mRNA export (By similarity). Forms a complex with RANBP2/NUP358, NXT1 and RANGAP1 (By similarity). Associates with the exon junction complex (EJC) (PubMed:12093754). Associates with the transcription/export (TREX) complex (By similarity). Found in a mRNA complex with UPF3A and UPF3B (By similarity). Found in a post-splicing complex with RBM8A, UPF1, UPF2, UPF3A, UPF3B and RNPS1 (By similarity). Interacts (via N-terminus) with DHX9 (via N-terminus); this interaction is direct and negatively regulates NXF1-mediated nuclear export of constitutive transport element (CTE)-containing cellular mRNAs (By similarity). Interacts with FYTTD1/UIF (By similarity). Interacts with EIF4A3 (By similarity). Interacts with NUP42 (By similarity). Interacts with ALYREF/THOC4 (PubMed:10786854). Interacts with CHTOP (By similarity). Interacts with FRG1 (via N-terminus) (By similarity). Interacts with LUZP4 (By similarity). Interacts with FMR1; the interaction occurs in a mRNA-dependent and polyribosomes-independent manner in the nucleus (By similarity). Interacts with CPSF6 (via N-terminus); this interaction is direct (By similarity). Interacts with RBM15 (By similarity). Interacts with RBM15B (By similarity). Interacts with MCM3AP; this interaction is not mediated by RNA (By similarity). Interacts with DDX3X (via C-terminus); this interaction may be partly involved in DDX3X nuclear export and in NXF1 localization to stress granules. Interacts with PABPC1/PABP1 (By similarity).|||Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex. ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export. Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export.|||Nucleus envelope|||Nucleus speckle|||Stress granule|||The NTF2 domain is functional only in the presence of NXT1 and is essential for the export of mRNA from the nucleus. It inhibits RNA binding activity through an intramolecular interaction with the N-terminal RNA binding domain (RBD); the inhibition is removed by an association with the TREX complex, specifically involving ALYREF/THOC4 and THOC5.|||The RNA-binding domain is a non-canonical RNP-type domain.|||The TAP-C domain mediates direct interactions with nucleoporin-FG-repeats and is necessary and sufficient for localization of NXF1 to the nuclear rim. The conserved loop 594-NWD-596 of the TAP-C domain has a critical role in the interaction with nucleoporins.|||The leucine-rich repeats are essential for the export of mRNA from the nucleus.|||The minimal CTE binding domain consists of an RNP-type RNA binding domain (RBD) and leucine-rich repeats.|||The nucleoporin binding domain consists of a NTF2 domain (also called NTF2-like domain) and a TAP-C domain (also called UBA-like domain). It has 2 nucleoporin-FG-repeats binding sites (one in the NTF2 and the other in the TAP-C domain) which contribute to nucleoporin association and act synergistically to export cellular mRNAs.|||nuclear pore complex|||nucleoplasm http://togogenome.org/gene/10090:Zbtb43 ^@ http://purl.uniprot.org/uniprot/Q9DAI4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with BDP1.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Ctbp2 ^@ http://purl.uniprot.org/uniprot/P56546|||http://purl.uniprot.org/uniprot/Q3UGL5|||http://purl.uniprot.org/uniprot/Q91YZ2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.|||Corepressor targeting diverse transcription regulators. Isoform 2 probably acts as a scaffold for specialized synapses (By similarity). Functions in brown adipose tissue (BAT) differentiation.|||Found in all tissues except spleen and liver.|||Interacts with HIPK2 and PNN (By similarity). Interacts with the transcription factors ZNF217, BKLF, delta EF1/AREB6/ZEB, EVI-1 and Friend of GATA (FOG) via the consensus motif P-X-[DNS]-L-[STVA]. Interacts also with the C-terminus of adenovirus E1A protein. Can form a complex with BKLF on a CACCC-box oligonucleotide. Can form homodimers or heterodimers of CTBP1 and CTBP2. Interacts with NRIP1 and WIZ. Interacts with PRDM16; represses white adipose tissue (WAT)-specific genes expression. Interacts with MCRIP1 (By similarity).|||Nucleus|||Phosphorylation by HIPK2 on Ser-428 induces proteasomal degradation.|||Strong expression confined to the embryonic stages.|||Synapse http://togogenome.org/gene/10090:Spata6 ^@ http://purl.uniprot.org/uniprot/Q3U6K5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPATA6 family.|||Interacts with MYL6.|||Knockout experiments to inactivate Spata6 were first attempted but were unsuccessful, because chimeras did not transmit the targeted allele to their progeny, generating high-percentage of lethality for chimeric embryos (PubMed:12771232). This suggests that genes other than Spata6 may have been targeted or affected in this study (PubMed:25605924).|||Male are sterile due to disruption of sperm connecting piece formation, leading to acephalic spermatozoa in the epididymis and ejaculates.|||Required for formation of the sperm connecting piece during spermiogenesis. Sperm connecting piece is essential for linking the developing flagellum to the head during late spermiogenesis (PubMed:12771232, PubMed:25605924). May be involved in myosin-based microfilament transport through interaction with myosin subunits (PubMed:25605924).|||Secreted|||Specifically expressed in developing spermatids and mature spermatozoa (at protein level) (PubMed:25605924). Isoform 1 is weakly expressed in testis, ovary, thymus and placenta. Isoform 2 and isoform 3 are testis-specific. Expression isw higher in spermatids than in spermatocytes and spermatogonia (PubMed:12771232).|||Weak expression of isoform 1 is seen throughout testicular development. Isoform 2 and isoform 3 could not be detected until postnatal day 15. Expressed from postnatal day 20, and thereafter increased. Expressed in blastocysts and in embryos from 8.5 dpc-12.5 dpc. After 13.5 dpc, the level of expression decreases. Expressed at 9.5-10.5 dpc in the neural tube, in somites and limb buds.|||flagellum http://togogenome.org/gene/10090:Ndn ^@ http://purl.uniprot.org/uniprot/P25233 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the transactivation domains of E2F1 and p53. Binds also SV40 large T antigen and adenovirus E1A. Interacts with nucleobindin 1 and 2.|||Brain specific. Not detected in other tissues. Expressed in postmitotic neurons. In adult brain the highest expression is in hypothalamus. Highly expressed in thalamus and midbrain. Relatively low levels are in cerebral cortex, hippocampus, striatum, olfactory bulb, cerebellum, pons and spinal cord. Also detected in neurally differentiated embryonal carcinoma cells.|||Cytoplasm|||Expression levels were high during embryonic and neonatal periods (14 dpc to P7) and decreased thereafter.|||Growth suppressor that facilitates the entry of the cell into cell cycle arrest. Functionally similar to the retinoblastoma protein it binds to and represses the activity of cell-cycle-promoting proteins such as SV40 large T antigen, adenovirus E1A, and the transcription factor E2F. Necdin also interacts with p53 and works in an additive manner to inhibit cell growth. Also functions as a transcription factor and directly binds to specific guanosine-rich DNA sequences.|||Nucleus matrix|||nucleoplasm http://togogenome.org/gene/10090:Atp8b5 ^@ http://purl.uniprot.org/uniprot/A3FIN4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Highly expressed in testis.|||Not detected in testis until 18 days postpartum. At 22 days postpartum, levels increase and remain constant during adulthood. During spermatogenesis, expressed from pachytene spermatocytes to mature sperm.|||P4-ATPase flippase which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. May play a role in phospholid transport across membranes and in acrosome formation.|||acrosome membrane http://togogenome.org/gene/10090:Sowahc ^@ http://purl.uniprot.org/uniprot/Q8C0J6 ^@ Similarity ^@ Belongs to the SOWAH family. http://togogenome.org/gene/10090:Mrgpra2b ^@ http://purl.uniprot.org/uniprot/E9QNZ7|||http://purl.uniprot.org/uniprot/Q91WW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed in a subset of sensory neurons that includes nociceptors. Expressed in the subclass of non-peptidergic sensory neurons that are IB4(+) and VR1(-).|||Membrane|||Orphan receptor. May be a receptor for RFamide-family neuropeptides such as NPFF and NPAF, which are analgesic in vivo. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Eif1ad2 ^@ http://purl.uniprot.org/uniprot/Q3UT53 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Atxn7l3 ^@ http://purl.uniprot.org/uniprot/A2AWT3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SGF11 family.|||Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H, TAF10, TRRAP and USP22. Within the SAGA complex, ENY2, ATXN7, ATXN7L3, and USP22 form an additional subcomplex of SAGA called the DUB module (deubiquitination module). Interacts directly with ENY2 and USP22.|||Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. Within the complex, it is required to recruit USP22 and ENY2 into the SAGA complex. Regulates H2B monoubiquitination (H2Bub1) levels. Affects subcellular distribution of ENY2, USP22 and ATXN7L3B.|||Nucleus|||The C-terminal SGF11-type zinc-finger domain together with the C-terminal catalytic domain of USP22 forms the 'catalytic lobe' of the SAGA deubiquitination module.|||The long N-terminal helix forms part of the 'assembly lobe' of the SAGA deubiquitination module. http://togogenome.org/gene/10090:Wdhd1 ^@ http://purl.uniprot.org/uniprot/P59328 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Core replisome component that acts as a replication initiation factor. Binds directly to the CMG complex and functions as a hub to recruit additional proteins to the replication fork.|||Trimer. Interacts with the polymerase alpha catalytic subunit POLA1. Interacts with MCM10. Interacts with DNA2. Interacts with CDC45 and GINS2 subunit of GINS complex; these interactions associate WDHD1 with the CMG helicase complex.|||nucleoplasm http://togogenome.org/gene/10090:Ndufaf4 ^@ http://purl.uniprot.org/uniprot/Q9D1H6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NDUFAF4 family.|||Binds calmodulin. Interacts with NDUFAF3.|||May be involved in cell proliferation and survival of hormone-dependent tumor cells. Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) (By similarity).|||Membrane|||Mitochondrion|||Phosphorylated on serine. Prolactin stimulate serine phosphorylation (By similarity). http://togogenome.org/gene/10090:Kmt2b ^@ http://purl.uniprot.org/uniprot/F8WJ40|||http://purl.uniprot.org/uniprot/O08550|||http://purl.uniprot.org/uniprot/Q6PHU4 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.|||Component of the menin-associated histone methyltransferase complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, DPY30, MEN1; the complex interacts with POLR2A and POLR2B via MEN1 (By similarity). Interacts with NFE2 (By similarity). Interacts with KDM6B (By similarity). Interacts (via WIN motif) with WDR5 (By similarity). Interacts (via MBM motif) with MEN1 (By similarity).|||Females are infertile due to anovulation and follicle loss. Oocytes show reduced H3K4me3 but not H3K4me1, abnormal expression of pro-apoptotic genes and Iap elements (which may contribute to oocyte death and, ultimately, follicle loss) and fail to establish transcriptional repression.|||Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (By similarity). Likely plays a redundant role with KMT2C in enriching H3K4me1 marks on primed and active enhancer elements (By similarity). Plays a central role in beta-globin locus transcription regulation by being recruited by NFE2 (By similarity). Plays an important role in controlling bulk H3K4me during oocyte growth and preimplantation development (PubMed:20808952). Required during the transcriptionally active period of oocyte growth for the establishment and/or maintenance of bulk H3K4 trimethylation (H3K4me3), global transcriptional silencing that preceeds resumption of meiosis, oocyte survival and normal zygotic genome activation (PubMed:20808952).|||Nucleus|||Possible contaminating sequence. The N-terminal 3 residues and C-terminal 8 residues do not match the underlying genomic sequence.|||The CXXC zinc finger mediates binding to DNA containing unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides.|||The human ortholog, KMT2B/MLL4, was first named MLL2 (see AC Q9UMN6). Thus, mouse Kmt2b/Mll4 is also often referred to as Mll2 and vice versa in the literature. http://togogenome.org/gene/10090:Vmn2r60 ^@ http://purl.uniprot.org/uniprot/A0A3B2WBC8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam170b ^@ http://purl.uniprot.org/uniprot/E9PXT9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM170 family.|||Exclusively expressed in adult testis (at protein level). Expression first started at postnatal week 3 in round spermatids, elongated spermatids and mature sperm.|||Interacts with GOPC.|||Plays a role in fertilization through the acrosome reaction.|||acrosome|||acrosome outer membrane http://togogenome.org/gene/10090:Or5b21 ^@ http://purl.uniprot.org/uniprot/Q0VEZ4|||http://purl.uniprot.org/uniprot/Q8VFX2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Opalin ^@ http://purl.uniprot.org/uniprot/Q3USW3|||http://purl.uniprot.org/uniprot/Q7M750 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By leukemia inhibitory factor (LIF) and cAMP analogs. Suppressed in the presence of astrocytic or neural-stem-like differentiation factors such as bone morphotic protein (BMP) and fetal calf serum.|||Cell membrane|||Central nervous system-specific myelin protein that increase myelin genes expression during oligodendrocyte differentiation. Promotes oligodendrocyte terminal differentiation.|||Deficient mice are born the expected Mendelian ratio and have a normal body shape and weight. No obvious abnormalities in gross anatomy or major myelin protein components nor in the compartment of myelinated axons and oligodendrocyte maturation. Nevertheless, deficient mice display increased exploratory activity in a novel environment.|||Expressed specifically in oligodendrocytes of the brain.|||Expression in the cerebellum increases dramatically after the first postnatal week (PubMed:18490449, PubMed:30837646). Selectively expressed in brain at P21, and not expressed in any other tissues tested including thymus, lung, heart, liver, spleen, kidney and testis.|||Membrane http://togogenome.org/gene/10090:Foxp4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J161|||http://purl.uniprot.org/uniprot/A0A0R4J1I5|||http://purl.uniprot.org/uniprot/Q9DBY0 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the adult heart, brain, spleen lung, liver, kidney and testes.|||Expressed predominantly in the lung and brain during embryogenesis. Expressed in the lung epithelium and the mesenchyme immediately adjacent to the epithelium from 10.5 dpc. At 9.5 dpc, expressed in the foregut endoderm but not in the heart. At 16.5 and 18.5 dpc, expressed in both the proximal and distal airway epithelium. Also expressed in the developing gut. In the hindgut, primarily expressed in epithelial cells of the intestine and stomach. Expressed in the brain in a dynamic pattern. At 14.5 dpc, expressed at high levels in the intermediate zone of the neopallial cortex with lower levels in the surrounding cells. By 16.5 dpc, no longer expressed in the intermediate zone, but still present in the surrounding cells of the neopallial cortex.|||Forms homodimers and heterodimers with FOXP1 and FOXP2. Dimerization is required for DNA-binding.|||Nucleus|||The leucine-zipper is required for dimerization and transcriptional repression.|||Transcriptional repressor that represses lung-specific expression. http://togogenome.org/gene/10090:Serpina1a ^@ http://purl.uniprot.org/uniprot/A0A0A0MQA3|||http://purl.uniprot.org/uniprot/P07758 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin.|||Murine alpha-1-antitrypsin is represented by a cluster of up to 6 individual Serpina1-related genes. The precise complement of Serpina1-related genes present varies according to the strain of the animal.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity. http://togogenome.org/gene/10090:Tnfaip2 ^@ http://purl.uniprot.org/uniprot/Q61333 ^@ Developmental Stage|||Function|||Similarity ^@ Belongs to the SEC6 family.|||In 10-day embryos B94 is expressed prominently in the myocardium and in the aortic arch. By the 15th day of gestation, expression is restricted largely to the liver, the bone forming regions of the jaw, the aortic endothelium, and the nasopharynx: a pattern that is maintained until just prior to birth. Postnatally, expression shifts to the red pulp of the spleen and the thymic medulla.|||May play a role as a mediator of inflammation and angiogenesis. http://togogenome.org/gene/10090:Lrrc3b ^@ http://purl.uniprot.org/uniprot/Q8VCH9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the LRRC3 family.|||Membrane http://togogenome.org/gene/10090:Nipal1 ^@ http://purl.uniprot.org/uniprot/Q8BMW7 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a Mg(2+) transporter (PubMed:18667602). Can also transport other divalent cations such as Fe(2+), Sr(2+), Ba(2+), Mn(2+), Cu(2+) and Co(2+) but to a much less extent than Mg(2+) (PubMed:18667602). Shown to promote insulin content and secretion in Min6-K8 cells, particularly under conditions of hypomagnesemia (PubMed:32439805).|||Belongs to the NIPA family.|||Expressed in the pancreatic islets.|||Golgi apparatus membrane|||Up-regulated by low magnesium ion levels. http://togogenome.org/gene/10090:Ptger2 ^@ http://purl.uniprot.org/uniprot/Q543A9|||http://purl.uniprot.org/uniprot/Q62053 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle. http://togogenome.org/gene/10090:Calm2 ^@ http://purl.uniprot.org/uniprot/P0DP26|||http://purl.uniprot.org/uniprot/P0DP27|||http://purl.uniprot.org/uniprot/P0DP28 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calmodulin family.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2.|||Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.|||Interacts with CEP97, CCP110, MYO1C, TTN/titin and SRY. Interacts with MYO10. Interacts with RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity). Interacts with RYR1 (PubMed:18650434). Interacts with MYO5A (By similarity). Interacts with IQCF1 (PubMed:25380116). Interacts with SYT7 (PubMed:24569478). Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity). Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434). Interacts with PCP4; regulates calmodulin calcium-binding (By similarity). Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (By similarity).|||Interacts with CEP97, CCP110, MYO1C, TTN/titin and SRY. Interacts with MYO10. Interacts with RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport (By similarity). Interacts with RYR1 (PubMed:18650434). Interacts with MYO5A (PubMed:17151196). Interacts with IQCF1 (PubMed:25380116). Interacts with SYT7 (PubMed:24569478). Interacts with CEACAM1 (via cytoplasmic domain); this interaction is in a calcium dependent manner and reduces homophilic cell adhesion through dissociation of dimer (By similarity). Interacts with RYR2; regulates RYR2 calcium-release channel activity (PubMed:18650434). Interacts with PCP4; regulates calmodulin calcium-binding (By similarity). Interacts with the heterotetrameric KCNQ2 and KCNQ3 channel; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (By similarity). Interacts with alpha-synuclein/SNCA (By similarity). Interacts with SLC9A1 in a calcium-dependent manner (By similarity). In the absence of Ca(+2), interacts with GIMAP4 (via IQ domain) (PubMed:16569770). Interacts with SCN8A; the interaction modulates the inactivation rate of SCN8A (PubMed:23942337). Interaction with KIF1A; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility (By similarity). Interacts with KCNN3 (By similarity). Interacts with KCNQ1 (via C-terminus); forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (By similarity). Interacts with PIK3C3; the interaction modulates PIK3C3 kinase activity (By similarity). Interacts with HINT1; interaction increases in the presence of calcium ions (PubMed:31088288). Interacts with HINT3 (PubMed:31088288). Interacts with GARIN2; in mature sperm flagella (PubMed:29025071). Interacts with IQUB (PubMed:36417862). Interacts with SLC26A5 (via STAS domain); this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).|||Phosphorylation results in a decreased activity.|||The N-terminal and C-terminal lobes of CALM bind to the C-terminus of KCNQ1 in a clamp-like conformation. Binding of CALM C-terminus to KCNQ1 is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to KCNQ1 is calcium-dependent and regulates electrophysiological activity of the channel.|||This protein has four functional calcium-binding sites.|||Ubiquitination results in a strongly decreased activity.|||centrosome|||flagellum|||spindle|||spindle pole http://togogenome.org/gene/10090:Kank4 ^@ http://purl.uniprot.org/uniprot/Q6P9J5 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||May be involved in the control of cytoskeleton formation by regulating actin polymerization. http://togogenome.org/gene/10090:Mrpl48 ^@ http://purl.uniprot.org/uniprot/Q8JZS9 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL48 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity). Interacts with OXA1L (By similarity).|||Contaminating sequence. Vector contamination at the N-terminus.|||Mitochondrion http://togogenome.org/gene/10090:Ptprt ^@ http://purl.uniprot.org/uniprot/B1AQN2|||http://purl.uniprot.org/uniprot/Q99M80 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.|||Exceptionally high levels found in the cortex and olfactory bulbs during perinatal development and are down-regulated during postnatal week 2. Expression in the cerebellar cortex is restricted to the granule cell layer of lobules 1-6. Anterior and posterior compartments become discernible only during postnatal weeks 2 and 6.|||Expression is restricted to the CNS. Distributed throughout the brain and spinal cord.|||May be involved in both signal transduction and cellular adhesion in the CNS. May have specific signaling roles in the tyrosine phosphorylation/dephosphorylation pathway in the anterior compartment of the adult cerebellar cortex.|||Membrane http://togogenome.org/gene/10090:Ncbp2 ^@ http://purl.uniprot.org/uniprot/Q9CQ49 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM NCBP2 family.|||Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus (By similarity).|||Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA (By similarity). Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA (PubMed:10786834). Interacts with PHAX/RNUXA, EIF4G1, HNRNPF, HNRNPH1 and ALYREF/THOC4/ALY (By similarity). Interacts with SRRT/ARS2 and KPNA3 (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Cd19 ^@ http://purl.uniprot.org/uniprot/P25918 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected on B cells in spleen, bone marrow, thymus and lymph nodes (PubMed:12387743, PubMed:7542548, PubMed:20101619). Detected on peripheral blood lymphocytes (at protein level) (PubMed:7543183).|||Functions as coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes. Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (By similarity). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:9382888, PubMed:12387743, PubMed:20101619). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:7542548, PubMed:7543183, PubMed:9317126). Required for normal differentiation of B-1 cells (PubMed:7542548, PubMed:7543183, PubMed:12387743). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:7542548, PubMed:9317126, PubMed:12387743). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:7542548, PubMed:7543183, PubMed:12387743).|||Interacts with CR2/CD21. Part of a complex composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of mature B-cells. Interacts directly with CD81 (via the second extracellular domain); this interaction is initiated early during biosynthesis in the ER/pre-Golgi compartments and is essential for trafficking and compartmentalization of CD19 receptor on the cell surface of when phosphorylated on Tyr-346 and/or Tyr-376. Interacts with PLCG2 when phosphorylated on Tyr-402. Interacts with LYN. Interacts (when tyrosine phosphorylated) with the regulatory p85 subunit of phosphatidylinositol 3-kinase (PIK3R1 or PIK3R2).|||Membrane raft|||Mutant mice are born at the expected Mendelian ratio, thrive and are fertile (PubMed:7542548). Mutant mice display normal differentiation and expansion of pro-B cells, pre-B cells, immature B cells and resting mature B cells in bone marrow (PubMed:7542548, PubMed:7543183, PubMed:9317126). Number and surface phenotype of conventional B cells in spleen, Peyer's patch and lymph nodes appear normal (PubMed:7543183). In contrast, the numbers of B-1 cells are decreased to 10-20% of the normal values in the peritoneal cavity, together with a severe reduction of serum IgM levels (PubMed:7542548, PubMed:7543183, PubMed:12387743). Likewise, mutant mice display severely reduced serum IgG1 and IgE levels (PubMed:7543183). Mutant mice display severely reduced B cell responses to antigens, with a strong decrease in the production of serum antibodies after an antigenic challenge, and defective production of high-affinity antibodies (PubMed:7543183).|||Phosphorylated on tyrosine following B-cell activation (PubMed:20101619). Phosphorylated on tyrosine residues by LYN (By similarity). Tyrosine residues are phosphorylated sequentially after activation of the B cell receptor. Phosphorylation of Tyr-522 is extremely rapid, followed by phosphorylation at Tyr-402. In contrast, phosphorylation of Tyr-493 appears more slowly and is more transient, returning rapidly to basal levels (PubMed:20101619). http://togogenome.org/gene/10090:Tmem102 ^@ http://purl.uniprot.org/uniprot/Q3UPR7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with CSF2RB; this interaction occurs preferentially in the absence of CSF2.|||Selectively involved in CSF2 deprivation-induced apoptosis via a mitochondria-dependent pathway. http://togogenome.org/gene/10090:Or4s2b ^@ http://purl.uniprot.org/uniprot/A2AV13 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Erbb4 ^@ http://purl.uniprot.org/uniprot/Q61527 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligands trigger phosphorylation at specific tyrosine residues, thereby creating binding sites for scaffold proteins and effectors. Constitutively phosphorylated at a basal level when overexpressed in heterologous systems; ligand binding leads to increased phosphorylation. Phosphorylation at Tyr-1035 is important for interaction with STAT1. Phosphorylation at Tyr-1056 is important for interaction with PIK3R1. Phosphorylation at Tyr-1242 is important for interaction with SHC1. Phosphorylation at Tyr-1188 may also contribute to the interaction with SHC1. Isoform JM-A CYT-2 is constitutively phosphorylated on tyrosine residues in a ligand-independent manner. E4ICD2 but not E4ICD1 is phosphorylated on tyrosine residues (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.|||Binding of a cognate ligand leads to dimerization and activation by autophosphorylation on tyrosine residues. In vitro kinase activity is increased by Mg(2+) (By similarity).|||Cell membrane|||Embryonically lethal. Embryos die at about 10 dpc, due to defects in the development of myocardial trabeculae in the heart ventricle that lead to severely reduced embryonic blood flow. Mice also display aberrant innervation from and to the hindbrain, especially concerning the trigeminal, facial and acoustic ganglia. This is due to aberrant migration of a subpopulation of cranial neural crest cells.|||Isoform JM-A CYT-1 and isoform JM-A CYT-2 are processed by ADAM17. Proteolytic processing in response to ligand or 12-O-tetradecanoylphorbol-13-acetate stimulation results in the production of 120 kDa soluble receptor forms and intermediate membrane-anchored 80 kDa fragments (m80HER4), which are further processed by a presenilin-dependent gamma-secretase to release a cytoplasmic intracellular domain (E4ICD; E4ICD1/s80Cyt1 or E4ICD2/s80Cyt2, depending on the isoform). Membrane-anchored 80 kDa fragments of the processed isoform JM-A CYT-1 are more readily degraded by the proteasome than fragments of isoform JM-A CYT-2, suggesting a prevalence of E4ICD2 over E4ICD1. Isoform JM-B CYT-1 and isoform JM-B CYT-2 lack the ADAM17 cleavage site and are not processed by ADAM17, precluding further processing by gamma-secretase (By similarity).|||Isoform JM-A CYT-2 and isoform JM-B CYT-2 are expressed in cerebellum, cerebral cortex, spinal cord, medulla oblongata and eye, but the kidney expresses solely isoform JM-A CYT-2 and the heart solely isoform JM-B CYT-2.|||Mitochondrion|||Monomer in the absence of bound ligand. Homodimer or heterodimer with another ERBB family member upon ligand binding, thus forming heterotetramers. Interacts with EGFR and ERBB2. Interacts with DLG2 (via its PDZ domain), DLG3 (via its PDZ domain), DLG4 (via its PDZ domain) and SNTB2 (via its PDZ domain). Interacts with MUC1. Interacts (via its PPxy motifs) with WWOX. Interacts (via the PPxY motif 3 of isoform JM-A CYT-2) with YAP1 (via the WW domain 1 of isoform 1). Interacts (isoform JM-A CYT-1 and isoform JM-B CYT-1) with WWP1. Interacts (via its intracellular domain) with TRIM28. Interacts (via the intracellular domains of both CYT-1 and CYT-2 isoforms) with KAP1; the interaction does not phosphorylate KAP1 but represses ERBB4-mediated transcriptional activity. Interacts with PRPU, DDX23, MATR3, RBM15, ILF3, KAP1, U5S1, U2SURP, ITCH, HNRNPU, AP2A1, NULC, LEO1, WWP2, IGHG1, HXK1, GRB7 and SRRT. Interacts (phosphorylated isoform JM-A CYT-1 and isoform JM-B CYT-1) with PIK3R1. Interacts with SHC1. Interacts with GRB2. Interacts (soluble intracellular domain) with BCL2. Interacts (phosphorylated) with STAT1 (By similarity). Interacts with CBFA2T3. Interacts (soluble intracellular domain) with STAT5A.|||Nucleus|||Proteolytical processing generates E4ICD1 (s80Cyt1).|||Proteolytical processing generates E4ICD2 (s80Cyt2).|||Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.|||Ubiquitinated. During mitosis, the ERBB4 intracellular domain is ubiquitinated by the APC/C complex and targeted to proteasomal degradation. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are ubiquitinated by WWP1. The ERBB4 intracellular domain (E4ICD1) is ubiquitinated, and this involves NEDD4 (By similarity). http://togogenome.org/gene/10090:Ptgr2 ^@ http://purl.uniprot.org/uniprot/Q8VDQ1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NADP-dependent oxidoreductase L4BD family.|||Cytoplasm|||Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest activity towards 15-keto-PGE2. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.|||Highly expressed in the late phase of adipocyte differentiation (at protein level).|||Monomer.|||Widely expressed with highest levels in adipose tissues. http://togogenome.org/gene/10090:Asic3 ^@ http://purl.uniprot.org/uniprot/Q6X1Y6 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC3 subfamily.|||Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.|||Cell membrane|||Cytoplasm|||Expressed in liver, lung, kidney, testis, brain, eye and cochlea. Expressed in spiral ganglion and sensory hair cells of the organ of Corti in the cochlea (at protein level). Expressed in dorsal root ganglion innervating muscles and spinal chord. Expressed in peripheral sensory nerve termimals like nerves of the Meissner corpuscle, palisades of lanceolate nerve endings, site of mechanoreception in guard hair follicles, and Merkel cell-neurite complexes.|||Homotrimer or heterotrimer with other ASIC proteins (By similarity). Interacts with DLG4 and ASIC2 (By similarity). Interacts with LIN7B, MAGI1/BAIAP1 and GOPC. Interacts with STOM; this regulates channel activity.|||Mice display altered responses to mechanical and acid stimuli. They do not develop chronic hyperalgesia induced by repeated acid injection.|||Phosphorylated by PKA. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel (By similarity).|||Sensitized and potentiated by NPFF and NPSF. Inhibited by anti-inflammatory drugs, like salicylic acid (By similarity). Potentiated by FMRFamide-related neuropeptides. Regulated by lactate and Ca(2+). http://togogenome.org/gene/10090:Cdk5r2 ^@ http://purl.uniprot.org/uniprot/O35926 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activator of CDK5/TPKII.|||Belongs to the cyclin-dependent kinase 5 activator family.|||Cell membrane|||Heterodimer of a catalytic subunit and a regulatory subunit.|||Myristoylated. The Gly-2-Ala mutant is absent of the cell periphery, suggesting that a proper myristoylation signal is essential for the proper distribution of CDK5R2 (p39) (By similarity). http://togogenome.org/gene/10090:Ubac2 ^@ http://purl.uniprot.org/uniprot/Q8R1K1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with LMBR1L, FAF2, AMFR and VCP.|||Restricts trafficking of FAF2 from the endoplasmic reticulum to lipid droplets (By similarity). In association with LMBR1L and E3 ubiquitin-protein ligase AMFR, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (PubMed:31073040). http://togogenome.org/gene/10090:Clpp ^@ http://purl.uniprot.org/uniprot/O88696 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S14 family.|||Detected in liver (at protein level). High levels found in heart, liver and skeletal muscle.|||Fourteen CLPP subunits assemble into 2 heptameric rings which stack back to back to give a disk-like structure with a central cavity. Component of the Clp complex formed by the assembly of two CLPP heptameric rings with two CLPX hexameric rings, giving rise to a symmetrical structure with two central CLPP rings flanked by a CLPX ring at either end of the complex.|||Homozygous pups are born at about 60 % of the expected Mendelian rate, indicating decreased intrauterine survival. Mutant mice are smaller in size than wild-type littermates, show decreased motor activity, are completely deaf after 12 months and their lifespan is decreased relative to that of wild-type littermates. Both female and male mutant mice are completely infertile due to defects in germ cell development.|||Mitochondrion matrix|||Protease component of the Clp complex that cleaves peptides and various proteins in an ATP-dependent process. Has low peptidase activity in the absence of CLPX. The Clp complex can degrade CSN1S1, CSN2 and CSN3, as well as synthetic peptides (in vitro) and may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates. Cleaves PINK1 in the mitochondrion. http://togogenome.org/gene/10090:Tmem47 ^@ http://purl.uniprot.org/uniprot/Q9JJG6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM47 family.|||Cell junction|||Expressed in podocytes (at protein level).|||Expression in kidney peaks at postnatal day 4 and declines to undetectable levels by day 15. In adults very low expression detected in the basal region of lateral membranes of few tubule segments (at protein level).|||Interacts with CTNNB1, CTNNA1, PRKCI, PARD6B (By similarity). Interacts with FYB1.|||Membrane|||Regulates cell junction organization in epithelial cells. May play a role in the transition from adherens junction to tight junction assembly. May regulate F-actin polymerization required for tight junctional localization dynamics and affect the junctional localization of PARD6B (PubMed:26990309). During podocyte differentiation may negatively regulate activity of FYN and subsequently the abundance of nephrin (PubMed:21881001).|||adherens junction http://togogenome.org/gene/10090:Pstpip1 ^@ http://purl.uniprot.org/uniprot/P97814 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cleavage furrow|||Cytoplasm|||Dephosphorylated on Tyr-344 by PTPN18, this event negatively regulates the association of PSTPIP1 with SH2 domain-containing proteins as tyrosine kinase. Phosphorylation of Tyr-344 is probably required for subsequent phosphorylation at other tyrosine residues. Phosphorylation is induced by activation of the EGFR and PDGFR in a ABL1 dependent manner. The phosphorylation regulates the interaction with WAS and with MEFV.|||Highly expressed in 7 dpc embryos.|||Highly expressed in adult lung and spleen, and weakly expressed in testis, muscle, kidney, brain and heart. Highly expressed in spleen and thymus, moderately in lung, brain and muscle, and weakly expressed in heart and liver (at protein level).|||Homodimer. Homotrimer. Interacts (via coiled-coil domain) with CD2AP, PTPN12 and PTPN18. Interacts (via SH3 domain) with ABL1 and WAS. Interacts (via SH3 and coiled-coil domains) with MEFV (via B-box zinc finger); the interaction allows binding of MEFV to PYCARD and facilitates formation of PYCARD pyroptosomes. Interacts with DNM2 and FASLG (By similarity). Interacts with CD2.|||Involved in regulation of the actin cytoskeleton. May regulate WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allow PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation. Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2. Also has a role in innate immunity and the inflammatory response. Recruited to inflammasomes by MEFV. Induces formation of pyroptosomes, large supramolecular structures composed of oligomerized PYCARD dimers which form prior to inflammatory apoptosis. Binding to MEFV allows MEFV to bind to PYCARD and facilitates pyroptosome formation. Regulates endocytosis and cell migration in neutrophils.|||The F-BAR domain is important for filament formation. The SH3 domain is not required for filament formation or localization to the uropod (By similarity).|||cytoskeleton|||lamellipodium|||perinuclear region|||uropodium http://togogenome.org/gene/10090:Cabp1 ^@ http://purl.uniprot.org/uniprot/Q9JLK7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ EF-1 binds magnesium constitutively under physiological conditions, EF-3 and EF-4 bind calcium cooperatively and EF-2 binds neither calcium nor magnesium.|||Expressed in the inner retina, specifically in amacrine cells and in cone OFF-bipolar cells (at protein level) (PubMed:27822497).|||Homodimer; when bound to calcium or magnesium. Interacts (via C-terminus) with ITPR1, ITPR2 and ITPR3. This binding is calcium dependent and the interaction correlates with calcium concentration. An additional calcium-independent interaction with the N-terminus of ITPR1 results in a decreased InsP(3) binding to the receptor (By similarity). Interacts with CACNA1A (via C-terminal CDB motif) in the pre- and postsynaptic membranes (By similarity). Interacts with CACNA1D and CACNA1C (via C-terminal C and IQ motifs). The binding to the C motif is calcium independent whereas the binding to IQ requires the presence of calcium and is mutually exclusive with calmodulin binding (By similarity). Interacts with TRPC5 (via C-terminus). Interacts (via EF-hands 1 and 2) at microtubules with MAP1LC3B (By similarity). Interacts with MYO1C. Interacts (via EF-hands 1 and 2) with NSMF (via the central NLS-containing motif region), the interaction occurs in a calcium dependent manner after synaptic NMDA receptor stimulation and prevents nuclear import of NSMF. Interacts with SPACA9 homolog.|||Mice exhibit a normal retinal morphology but altered light responses of retinal ganglion cells (PubMed:27822497).|||Modulates calcium-dependent activity of inositol 1,4,5-triphosphate receptors (ITPRs). Inhibits agonist-induced intracellular calcium signaling. Enhances inactivation and does not support calcium-dependent facilitation of voltage-dependent P/Q-type calcium channels (By similarity). Causes calcium-dependent facilitation and inhibits inactivation of L-type calcium channels by binding to the same sites as calmodulin in the C-terminal domain of CACNA1C, but has an opposite effect on channel function. Suppresses the calcium-dependent inactivation of CACNA1D (PubMed:17050707, PubMed:17947313). Inhibits TRPC5 channels. Prevents NMDA receptor-induced cellular degeneration (By similarity). Required for the normal transfer of light signals through the retina (PubMed:27822497).|||Phosphorylated. The phosphorylation regulates the activity (By similarity). http://togogenome.org/gene/10090:Sirt5 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VM56|||http://purl.uniprot.org/uniprot/Q8K2C6 ^@ Caution|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sirtuin family. Class III subfamily.|||Binds 1 zinc ion per subunit.|||Detected in brain, liver, heart, kidney, lung, thymus, spleen, skeletal muscle, intestine, pancreas and testis (at protein level).|||In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity.|||Mice are born at an abnormal Mendelian ratio with the number of live-born pups reduced by 40% (PubMed:24076663). Surviving mice display a global protein hypersuccinylation and hyperglutarylation in both liver and skeletal muscle, while global lysine acetylation is not significantly impacted (PubMed:22076378, PubMed:24315375, PubMed:23806337, PubMed:24703693). Mice display elevated levels of blood ammonia during fasting, but otherwise are metabolically similar to wild-type (PubMed:24076663). No overt phenotype observed in mice on chow or high fat diet, suggesting that Sirt5 may be dispensable for basal homeostasis under these conditions (PubMed:24076663). After 48 hours of fasting, the absence of Cps1 activation leads to elevated blood ammonia levels, possibly due to the presence of succinylation at 'Lys-1291' in Cps1 (PubMed:22076378). Animals show a decrease of fatty acid oxidation and increase of acylcarnitines accumulation (PubMed:24315375).|||Mitochondrion|||Monomer. Homodimer (By similarity). Interacts with CPS1 (PubMed:19410549). Interacts with PCCA (PubMed:23438705).|||Monomer. Homodimer. Interacts with CPS1.|||NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:23806337, PubMed:21908771, PubMed:22076378, PubMed:24315375, PubMed:24703693). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:19410549, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (By similarity). Activates SHMT2 by mediating its desuccinylation (By similarity). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (PubMed:24315375). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as Uox (PubMed:23085393).|||NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as Uox.|||Nucleus|||The ability to deacetylate Uox in vivo is unclear. The anti-acetylated lysine antibody used in the assay is not fully specific and cross-reacts with some acylated lysines. It is therefore possible that it also recognizes N6-malonyllysine and N6-succinyllysine residues (PubMed:23085393).|||cytosol http://togogenome.org/gene/10090:Supt4a ^@ http://purl.uniprot.org/uniprot/P63271 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPT4 family.|||Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (By similarity).|||Interacts with SUPT5H to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of WHSC2/NELFA, COBRA1/NELFB, TH1L/NELFD and RDBP/NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with HRMT1L2/PRMT1, HTATSF1/TATSF1, RNGTT/CAP1A, SKB1/PRMT5, SUPT6H, and can interact with PIN1 (By similarity).|||Nucleus|||Widely expressed. http://togogenome.org/gene/10090:Stap1 ^@ http://purl.uniprot.org/uniprot/Q9JM90 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expression restricted to the bone marrow.|||Interacts with URI1; the interaction is phosphorylation-dependent occurs in a growth-dependent manner (By similarity). Interacts with KIT and CSF1R.|||May function as an adapter molecule downstream of KIT in the proliferation or differentiation of hematopoietic stem cells.|||Mitochondrion|||Nucleus|||Phosphorylated on tyrosine by TEC. Phosphorylated on tyrosine by KIT. http://togogenome.org/gene/10090:Grik3 ^@ http://purl.uniprot.org/uniprot/B1AS29 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK3 subfamily.|||Cell membrane|||Detected in whole brain, cerebellum, brain cortex and hippocampus.|||Homotetramer, and heterotetramer with either GRIK4 or GRIK5. Interacts with PRKCABP (By similarity). Interacts with NETO2 (By similarity).|||Postsynaptic cell membrane|||Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA (By similarity). http://togogenome.org/gene/10090:Nup58 ^@ http://purl.uniprot.org/uniprot/Q8R332 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NUP58 family.|||Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane.|||Component of the p62 complex, a complex at least composed of NUP62, NUP54, and NUP58. Interacts with NUTF2. Interacts with SRP1-alpha and Importin p97 proteins when they are together, but not with SRP1-alpha protein alone (By similarity).|||Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited.|||In rat, the p62 complex contains two different isoforms of NUP58. Isoform p45 has however not been isolated in mouse so far.|||Nucleus membrane|||O-glycosylated.|||nuclear pore complex http://togogenome.org/gene/10090:Meox1 ^@ http://purl.uniprot.org/uniprot/P32442 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ After 7 dpc it is expressed in mesoderm lying posterior of the future primordial head and heart. Between 7.5 and 9.5 dpc it is expressed in presomitic mesoderm, epithelial and differentiating somites and in lateral plate mesoderm. In the body of mid-gestation embryos it is restricted to loose undifferentiated mesenchyme.|||Cytoplasm|||Heart, lateral plate derivatives, kidney, loose connective tissue at sites of bone formation and skeletal muscle-connective tissue apposition.|||Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development. Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints (PubMed:19520072). Binds specifically to the promoter of target genes and regulates their expression. Activates expression of NKX3-2 in the sclerotome (PubMed:15024065). Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation. While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner (PubMed:22206000). Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome (By similarity).|||Mice display mild defects in sclerotome derived vertebral and rib bones (PubMed:12925591). Abnormalities are restricted to the sclerotome and its derivatives and are characterized by a remodeling of the cranio-cervical joints, leading to the assimilation of the atlas into the basioccipital bone so that the skull rests on the axis (PubMed:19520072). Mice lacking Meox1 and Meox2 show extremely disrupted somite morphogenesis, patterning and differentiation. They lack an axial skeleton and skeletal muscles are severely deficient (PubMed:12925591).|||Nucleus http://togogenome.org/gene/10090:Il4i1b ^@ http://purl.uniprot.org/uniprot/D3Z4E0|||http://purl.uniprot.org/uniprot/O09046 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the flavin monoamine oxidase family.|||Belongs to the flavin monoamine oxidase family. FIG1 subfamily.|||By interleukin-4.|||Expression increases during bone marrow-derived macrophage (BMDM) differentiation: expression is much higher in primary macrophages than monocytes.|||Lysosome|||Mice display an accelerated B-cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B-cells.|||Primarily found in immune tissues, mostly in B-lymphocytes.|||Primarily found in immune tissues.|||Restricted to the testis, predominantly in Sertoli cells at the periphery of the ducts, and the brain, including Purkinje cells, hippocampus and mitral cells in the olfactory bulb. No isoform 2 expression in fetal tissues.|||Secreted|||Secreted L-amino-acid oxidase that acts as a key immunoregulator (PubMed:32818467). Has preference for L-aromatic amino acids: converts phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) to phenylpyruvic acid (PP), hydroxyphenylpyruvic acid (HPP), and indole-3-pyruvic acid (I3P), respectively (PubMed:15383589). Also has weak L-arginine oxidase activity (By similarity). Acts as a negative regulator of anti-tumor immunity by mediating Trp degradation via an indole pyruvate pathway that activates the transcription factor AHR (PubMed:21469114, PubMed:28405502, PubMed:32818467). IL4I1-mediated Trp catabolism generates I3P, giving rise to indole metabolites (indole-3-acetic acid (IAA) and indole-3-aldehyde (I3A)) and kynurenic acid, which act as ligands for AHR, a ligand-activated transcription factor that plays important roles in immunity and cancer (By similarity). AHR activation by indoles following IL4I1-mediated Trp degradation enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Also has an immunoregulatory function in some immune cell, probably by mediating Trp degradation and promoting downstream AHR activation: inhibits T-cell activation and proliferation, promotes the differentiation of naive CD4(+) T-cells into FOXP3(+) regulatory T-cells (Treg) and regulates the development and function of B-cells (PubMed:25778793, PubMed:29288206). Also regulates M2 macrophage polarization by inhibiting T-cell activation (PubMed:26599209). Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2 (By similarity).|||Uses the promoter of the upstream NUP62 gene and shares the first 2 non-coding exons with NUP62.|||acrosome http://togogenome.org/gene/10090:Six4 ^@ http://purl.uniprot.org/uniprot/Q61321 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc expressed at the surface ectoderm outside the neural folds, somites, presomitic mesoderm. At 9.5 dpc expressed at the nasal and otic placodes, cranial ganglia, branchial arches, somites (dermamyotomes and sclerotomes). At 10.5-11.5 dpc expressed at the nasal pits, otic vesicles, cranial ganglia, dorsal root ganglia, branchial arches, somites, myotomes, limb mesenchyme, notochord, mesonephros. At 12.5-13.5 dpc expressed in skeletal muscles, mesenchyme in limbs and digits, nasal epithelium, inner ear (PubMed:11313460). Weakly expressed in the nephrogenic cord on 9.5 dpc and in the metanephric mesenchyme on 10.5 dpc (PubMed:17300925). At 11.5 dpc expressed in the epithelium of the lateral lingual swellings, and in the tongue epithelium, mesenchyme, and muscles at 12.5 dpc. In the fungiform papillae, expressed in the epithelium at 14-16.5 dpc. In the circumvallate and foliate papillae, expression is observed in the trench wall of these papillae at 15.5 dpc-P0 (PubMed:21978088). At 11.5 dpc mainly found in limbs, and somites, where is expressed in the dorsal root ganglion, myotomes, and ventral and dorsal dermomyotomal lips (PubMed:15788460). Expressed in a wide domain of the ectoderm in the presumptive olfactory region and in the thickened olfactory placode. Expressed in the peripheral precursors of the pit. At 12.5 dpc-14.5 dpc, expression become progressively restricted to the apical and basal progenitors.Also expressed strongly in the preplacodal region at 8.0 dpc and in the presumptive olfactory ectoderm at 9.0 dpc (PubMed:19027001). At 10.5 dpc expressed in the progenitors of the dermomyotome and in the myocytes (PubMed:19962975).|||Belongs to the SIX/Sine oculis homeobox family.|||Cytoplasm|||Incomplete sequence.|||Interacts with EYA3; acts cooperatively with EYA3 to transactivate target genes through interaction and nuclear translocation of EYA3 protein (PubMed:12215533, PubMed:10490620).|||Mainly expressed in the skeletal muscle (isoform 1 and isoform 2 but not isoform 3), and weakly in the heart. Also found in the retina and the distal tube of kidney. Expressed in skeletal muscle, nasal epithelium, cochlea, parathyroid and salivary gland (PubMed:11313460). Expressed in muscle satellite cells of normal and regenerating muscles (PubMed:20696153).|||Mice are viable and fertile; no gross morphological or histological abnormalities, or defects in hearing ability are detected in homozygous mice (PubMed:11313460). Double homozygous SIX1 and SIX4 knockout mice die soon after birth and show developmental defects in various organs (PubMed:15955062). Double homozygous SIX1 and SIX4 knockout mice causes severe defects in the trigeminal ganglia (PubMed:16938278). Double homozygous SIX1 and SIX4 knockout mice exhibit more severe kidney phenotypes than the SIX1 knockout mice. Double homozygous SIX1 and SIX4 knockout embryos show distinct morphological changes: fusion of the lateral lingual swellings is delayed, and the tongue is poorly developed. The primordia of fungiform papillae appears earlier, and the papillae rapidly increases in size; thus fusion of each papilla is evident. The circumvallate papillae show severe defects: invagination of the trenches starts asymmetrically, which results in longer and shorter trenches (PubMed:21978088). Double homozygous SIX1 and SIX4 knockout neonatal mice have a male-to-female sex-reversal phenotype in XY mutant gonads (PubMed:23987514). Double homozygous SIX1 and SIX4 knockout neonatal mice are characterized by severe craniofacial and rib defects, and general muscle hypoplasia (PubMed:15788460).|||Nucleus|||Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a DNA sequence on these target genes and is involved in processes like cell differentiation, cell migration and cell survival. Transactivates gene expression by binding a 5'-[CAT]A[CT][CT][CTG]GA[GAT]-3' motif present in the Trex site and from a 5'-TCA[AG][AG]TTNC-3' motif present in the MEF3 site of the muscle-specific genes enhancer (PubMed:14966291). Acts cooperatively with EYA proteins to transactivate their target genes through interaction and nuclear translocation of EYA protein (PubMed:10490620). Acts synergistically with SIX1 to regulate target genes involved in formation of various organs, including muscle, kidney, gonad, ganglia, olfactory epithelium and cranial skeleton. Plays a role in several important steps of muscle development. Controls the genesis of hypaxial myogenic progenitors in the dermomyotome by transactivating PAX3 and the delamination and migration of the hypaxial precursors from the ventral lip to the limb buds through the transactivation of PAX3, MET and LBX1 (PubMed:15788460). Controls myoblast determination by transactivating MYF5, MYOD1 and MYF6 (PubMed:15788460, PubMed:17592144). Controls somitic differentiation in myocyte through MYOG transactivation (PubMed:15788460). Plays a role in synaptogenesis and sarcomere organization by participating in myofiber specialization during embryogenesis by activating fast muscle program in the primary myotome resulting in an up-regulation of fast muscle genes, including ATP2A1, MYL1 and TNNT3 (PubMed:19962975, PubMed:21884692). Simultaneously, is also able to activate inhibitors of slow muscle genes, such as SOX6, HRASLS, and HDAC4, thereby restricting the activation of the slow muscle genes (PubMed:21884692). During muscle regeneration, negatively regulates differentiation of muscle satellite cells through down-regulation of MYOG expression (PubMed:20696153). During kidney development regulates the early stages of metanephros development and ureteric bud formation through regulation of GDNF, SALL1, PAX8 and PAX2 expression (PubMed:17300925). Plays a role in gonad development by regulating both testis determination and size determination. In gonadal sex determination, transactivates ZFPM2 by binding a MEF3 consensus sequence, resulting in SRY up-regulation. In gonadal size determination, transactivates NR5A1 by binding a MEF3 consensus sequence resulting in gonadal precursor cell formation regulation (PubMed:23987514). During olfactory development mediates the specification and patterning of olfactory placode through fibroblast growth factor and BMP4 signaling pathways and also regulates epithelial cell proliferation during placode formation (PubMed:19027001). Promotes survival of sensory neurons during early trigeminal gangliogenesis (PubMed:16938278). In the developing dorsal root ganglia, up-regulates SLC12A2 transcription (PubMed:15955062). Regulates early thymus/parathyroid organogenesis through regulation of GCM2 and FOXN1 expression (PubMed:16530750). Forms gustatory papillae during development of the tongue (PubMed:21978088). Also plays a role during embryonic cranial skeleton morphogenesis (PubMed:20515681). http://togogenome.org/gene/10090:Stx11 ^@ http://purl.uniprot.org/uniprot/Q3U5V8|||http://purl.uniprot.org/uniprot/Q9D3G5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Interacts with the SNARE proteins SNAP-23 and VAMP.|||Membrane|||SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Fry ^@ http://purl.uniprot.org/uniprot/E9Q8I9 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the furry protein family.|||Cytoplasm|||May be due to an intron retention.|||Phosphorylated by AURKA, CDK1 and PLK1.|||Plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity by promoting PLK1 activity at the spindle poles in early mitosis. May function as a scaffold promoting the interaction between AURKA and PLK1, thereby enhancing AURKA-mediated PLK1 phosphorylation.|||When phosphorylated by CDK1, interacts with PLK1; this interaction occurs in mitotic cells, but not in interphase cells, and leads to further FRY phosphorylation by PLK1.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Etfdh ^@ http://purl.uniprot.org/uniprot/Q921G7 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts electrons from ETF and reduces ubiquinone.|||Acetylation of Lys-95 and Lys-222 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the ETF-QO/FixC family.|||Binds 1 [4Fe-4S] cluster.|||Mitochondrion inner membrane|||Monomer. http://togogenome.org/gene/10090:Gask1a ^@ http://purl.uniprot.org/uniprot/Q3UY90 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GASK family.|||Endoplasmic reticulum|||Expressed in tracheal serous gland, heart, muscle, fat, lung, ovary, liver, kidney, adrenal gland and brain (at protein level).|||Golgi apparatus|||Proteolytically cleaved. Cleaved at Arg-112 and Arg-424 leading to a processed mature product of 35 kDa. The cleavage takes place in the Golgi apparatus.|||Secreted|||caveola http://togogenome.org/gene/10090:Ccpg1 ^@ http://purl.uniprot.org/uniprot/Q640L3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an assembly platform for Rho protein signaling complexes. Limits guanine nucleotide exchange activity of MCF2L toward RHOA, which results in an inhibition of both its transcriptional activation ability and its transforming activity. Does not inhibit activity of MCF2L toward CDC42, or activity of MCF2 toward either RHOA or CDC42. May be involved in cell cycle regulation.|||Belongs to the CCPG1 family.|||Cytoplasmic granule membrane|||Interacts with MCF2L. May interact with MCF2, ARHGEF1, BCR, VAV1 and FGD1, but not with TIAM1. Interacts with GTP-bound CDC42 and SRC. http://togogenome.org/gene/10090:Coa5 ^@ http://purl.uniprot.org/uniprot/Q99M07 ^@ Function|||Similarity ^@ Belongs to the PET191 family.|||Involved in an early step of the mitochondrial complex IV assembly process. http://togogenome.org/gene/10090:Pak2 ^@ http://purl.uniprot.org/uniprot/Q8CIN4 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-402 and allows the kinase domain to adopt an active structure. Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34.|||Full-length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate (By similarity).|||Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with SCRIB. Interacts with ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10. Interacts with RAC1 (By similarity).|||Membrane|||Nucleus|||Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:11278362). Acts as downstream effector of the small GTPases CDC42 and RAC1 (By similarity). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (By similarity). Full-length PAK2 stimulates cell survival and cell growth (By similarity). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (By similarity). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (By similarity). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:11278362). Phosphorylates CASP7, thereby preventing its activity (By similarity). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (By similarity). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (By similarity). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (By similarity).|||Ubiquitinated, leading to its proteasomal degradation.|||perinuclear region http://togogenome.org/gene/10090:Ifi203 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0H6|||http://purl.uniprot.org/uniprot/E9PUG6|||http://purl.uniprot.org/uniprot/E9QAN9|||http://purl.uniprot.org/uniprot/O35368 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HIN-200 family.|||Constitutively expressed in the thymus, bone marrow and spleen. Isoform 1 and isoform 3 are present in liver (at protein level).|||Induced by alpha interferon (at protein level).|||Nucleus http://togogenome.org/gene/10090:H2al2b ^@ http://purl.uniprot.org/uniprot/A9Z055 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Ccdc22 ^@ http://purl.uniprot.org/uniprot/Q9JIG7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC22 family.|||Endosome|||Interacts with CPNE1 and CPNE4 (PubMed:12522145). Interacts with COMMD1, COMMD2 COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8, COMMD9, COMMD10. Interacts with CUL1, CUL2, CUL3, SKP1, BTRC. Interacts with CCDC93; proposed to be a component of the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22 and CCDC93; in the complex interacts directly with CCDC93. Interacts with VPS35L; associates with the retriever complex. Interacts with SNX17 and SNX31 (By similarity).|||Involved in regulation of NF-kappa-B signaling. Promotes ubiquitination of I-kappa-B-kinase subunit IKBKB and its subsequent proteasomal degradation leading to NF-kappa-B activation; the function may involve association with COMMD8 and a CUL1-dependent E3 ubiquitin ligase complex. May down-regulate NF-kappa-B activity via association with COMMD1 and involving a CUL2-dependent E3 ubiquitin ligase complex. Regulates the cellular localization of COMM domain-containing proteins, such as COMMD1 and COMMD10. Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels. The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1. Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes.|||centrosome http://togogenome.org/gene/10090:Mea1 ^@ http://purl.uniprot.org/uniprot/Q64327 ^@ Caution|||Developmental Stage|||Function|||Tissue Specificity ^@ Expressed as early as day 6 postpartum (dpp), with higher expression in the adult testis.|||Highly expressed in testis. Transcripts can be found in primary and secondary spermatocytes, and spermatids, but the protein itself is only detected in spermatids. No expression in Leydig cells, spermatogonia, or sperm. Very weak expression in the heart, kidney, spleen, thymus and ovary.|||It is uncertain whether Met-1 or Met-11 is the initiator.|||May play an important role in spermatogenesis and/or testis development.|||Was originally thought to be the H-Y antigen. http://togogenome.org/gene/10090:Wdr6 ^@ http://purl.uniprot.org/uniprot/Q99ME2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat WDR6 family.|||Cytoplasm|||Interacts with FTSJ1; the interaction is direct, and required for 2'-O-methylation of position 34 in substrate tRNAs (By similarity). Interacts with IRS4 (By similarity). Interacts with STK11/LKB1 (By similarity).|||Together with methyltransferase FTSJ1, methylates the 2'-O-ribose of nucleotides at position 34 of the tRNA anticodon loop of substrate tRNAs (By similarity). Required for the correct positioning of the substrate tRNA for methylation (By similarity). Required to suppress amino acid starvation-induced autophagy (By similarity). Enhances the STK11/LKB1-induced cell growth suppression activity (By similarity). http://togogenome.org/gene/10090:Eng ^@ http://purl.uniprot.org/uniprot/Q63961 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in embryo (at protein level). Detected in endothelium from yolk sac vessels.|||Detected on blood vessels (at protein level) (PubMed:8194490). Detected on adult pulmonary artery, capillaries supporting the heart muscle and lung alveolar capillary endothelial cells (PubMed:10625534). Endoglin is restricted to endothelial cells in all tissues except bone marrow and is also found in stromal cells within the connective tissue of intestine, stomach, heart, skeletal muscle, uterus, ovary, oviduct, testis and thymus (PubMed:8194490).|||Full embryonic lethality at about 10.5 dpc. At 9.5 dpc, embryos display abnormal yolk sac vasculature and yolk sac anemia. Mutant embryos are also anemic, probably due to defective hematopoiesis in the yolk sac. In contrast, the embryonic vasculature appears grossly normal in most cases, but heart development is abnormal, and nearly all mutant embryos had enlarged ventricles and dilated outflow tracts. Besides, many had abnormal cardiac looping and displayed pericardial effusion. Heterozygous mice have occasionally abnormally convoluted and dilated blood vessels with disorganized smooth muscle cells surrounding them; these blood vessels are very fragile and rupture easily.|||Homodimer; disulfide-linked (PubMed:8194490). Forms a heteromeric complex with the signaling receptors for transforming growth factor-beta: TGFBR1 and/or TGFBR2. Interacts with TGFB1 (PubMed:8194490). It is able to bind TGFB1 and TGFB2 with high affinity, but not TGFB3. Interacts with GDF2, forming a heterotetramer with a 2:2 stoichiometry. Interacts with ACVRL1. Can form a heteromeric complex with GDF2 and ACVRL1. Interacts with BMP10. Interacts with DYNLT4. Interacts with ARRB2.|||Lacks a RGD motif, contrary to the human protein.|||The N-terminal OR region is composed of two intertwined domains (OR1 and OR2) with a common, novel fold. Each contains 12 beta-strands that form a parallel beta-helix-like structure, plus a single alpha-helix. The OR1 region mediates interaction with GDF2.|||The ZP domain mediates dimerization.|||Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:10625534). Required for normal structure and integrity of adult vasculature (By similarity). Regulates the migration of vascular endothelial cells (PubMed:17540773). Required for normal extraembryonic angiogenesis and for embryonic heart development (PubMed:10625534). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (PubMed:28530658). May play a role in the binding of endothelial cells to integrins. Acts as TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors (PubMed:23300529). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (By similarity). http://togogenome.org/gene/10090:Mymk ^@ http://purl.uniprot.org/uniprot/E9QA72|||http://purl.uniprot.org/uniprot/Q9D1N4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM8 family.|||Cell membrane|||During embryogenesis, highly expressed in the myotome compartment of the somites, and later in limb buds and axial skeletal muscles. Specifically expressed in skeletal muscle, and not in other muscle tissues or non-muscle tissues. Expression is down-regulated postnatally.|||Expression is induced in muscles in response to muscle injury (PubMed:25085416). Expression is induced in muscle progenitors response to muscle overload (PubMed:28186492). Down-regulated by in microRNA miR-491, which binds specifically to its 3' untranslated region of Mymk leading to its down-regulation (PubMed:28579197).|||Golgi apparatus membrane|||Interacts with MYMX (PubMed:28386024).|||Membrane|||Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers (PubMed:23868259, PubMed:28386024, PubMed:28681861, PubMed:30197239). Actively participates in the membrane fusion reaction by mediating the mixing of cell membrane lipids (hemifusion) upstream of MYMX (PubMed:30197239). Acts independently of MYMX (PubMed:30197239). Involved in skeletal muscle regeneration in response to injury by mediating the fusion of satellite cells, a population of muscle stem cells, with injured myofibers (PubMed:25085416). Also involved in skeletal muscle hypertrophy, probably by mediating the fusion of satellite cells with myofibers (PubMed:28186492).|||Palmitoylated at the C-terminus; palmitoylation promotes localization to the Golgi apparatus.|||Perinatal death due to an absence of multi-nucleated muscle fibers (PubMed:23868259). Mice are observed at normal Mendelian ratios at 15 dpc and 17.5 dpc, full-term embryos are alive but are paralyzed and kyphotic with flaccid limbs due to skeletal muscle deficiency (PubMed:23868259). They show a complete absence of differentiated muscle tissue in the trunk, limbs or head (PubMed:23868259). Myoblasts can activate muscle-specific gene expression and differentiate, but lack the ability to fuse (PubMed:23868259). Defects are caused by impaired lipid mixing of cell membranes (PubMed:30197239). Conditional deletion in adult satellite cells, a population of muscle stem cells, completely abolishes muscle regeneration after injury, resulting in severe muscle destruction (PubMed:25085416). Conditional deletion in adult satellite cells impairs skeletal muscle hypertrophy in response to exercise (PubMed:28186492).|||Specifically expressed in skeletal muscle during embryogenesis and adult muscle regeneration. http://togogenome.org/gene/10090:Crygb ^@ http://purl.uniprot.org/uniprot/P04344 ^@ Domain|||Function|||Miscellaneous|||Similarity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||There are six different gamma crystallins identified in mouse lens. http://togogenome.org/gene/10090:C4bp ^@ http://purl.uniprot.org/uniprot/P08607 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. Alpha chain binds C4b. It interacts also with serum amyloid P component.|||Homoheptamer; not covalently linked. Mouse lacks the beta chain of C4BP.|||It is uncertain whether Met-1 or Met-44 is the initiator.|||Secreted http://togogenome.org/gene/10090:Myo18a ^@ http://purl.uniprot.org/uniprot/A0A1C7ZN10|||http://purl.uniprot.org/uniprot/B2RRE2|||http://purl.uniprot.org/uniprot/E9Q405|||http://purl.uniprot.org/uniprot/E9QAX2|||http://purl.uniprot.org/uniprot/Q9JMH9 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cytoplasm|||Endoplasmic reticulum-Golgi intermediate compartment|||Golgi apparatus|||Golgi outpost|||Homodimer. Forms a tripartite complex with CDC42BPA/CDC42BPB and LURAP1 with the latter acting as an adapter connecting CDC42BPA/CDC42BPB and MYO18A (By similarity). Binds F-actin; regulated by ADP and GOLPH3 (PubMed:15582604). Interacts with GOLPH3; the interaction is direct and may link Golgi membranes to the actin cytoskeleton (By similarity). Interacts with JAK3 (PubMed:10733938). Interacts with MSR1 and CD14 (By similarity).|||Isoform 1; Expressed ubiquitously. Isoform 2: Specifically expressed in most hematopoietic cells. Isoform 3: Predominantly expressed in alveolar macrophages (PubMed:25965346).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (By similarity). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (PubMed:10733906). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (By similarity).|||Phosphorylated on tyrosine upon CSF1R activation. Isoform 6 is phosphorylated on Ser-340.|||The myosin motor domain binds ADP and ATP but has no intrinsic ATPase activity. Mediates ADP-dependent binding to actin (By similarity).|||cytoskeleton|||microtubule organizing center|||trans-Golgi network http://togogenome.org/gene/10090:Espl1 ^@ http://purl.uniprot.org/uniprot/P60330 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autocleaves. This function, which is not essential for its protease activity, is unknown (By similarity).|||Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms (By similarity).|||Cytoplasm|||Interacts with PTTG1. Interacts with RAD21 (By similarity).|||Nucleus|||Phosphorylated by CDK1. There is 8 Ser/Thr phosphorylation sites. Among them, only Ser-1121 phosphorylation is the major site, which conducts to the enzyme inactivation (By similarity).|||Regulated by at least two independent mechanisms. First, it is inactivated via its interaction with securin/PTTG1, which probably covers its active site. The association with PTTG1 is not only inhibitory, since PTTG1 is also required for activating it, the enzyme being inactive in cells in which PTTG1 is absent. PTTG1 degradation at anaphase, liberates it and triggers RAD21 cleavage. Second, phosphorylation at Ser-1121 inactivates it. The complete phosphorylation during mitosis, is removed when cells undergo anaphase. Activation of the enzyme at the metaphase-anaphase transition probably requires the removal of both securin and inhibitory phosphate (By similarity). http://togogenome.org/gene/10090:Tet3 ^@ http://purl.uniprot.org/uniprot/A0A5K1VVP6|||http://purl.uniprot.org/uniprot/Q8BG87 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TET family.|||Binds 1 Fe(2+) ion per subunit.|||Chromosome|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming during embryonic development.|||Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By similarity).|||Expressed maternally. Expressed at high levels in germinal vesicle (GV) stage and MII-stage oocytes. Expressed at lower levels in one-cell embryos until 4-cell stage. Hardly detectable in morula. Expressed mainly in somatic cells from 9.5 dpc until at least 16.5 dpc. Expression in primordial germ cells is undetectable until 13.5 dpc and peaks at 16.5 dpc (PubMed:23151479).|||Highly expressed in germinal vesicle (GV) stage and MII-stage oocytes and in early embryos.|||Interacts with HCFC1 (By similarity). Interacts with OGT (By similarity). Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex (By similarity).|||Monoubiquitinated at Lys-1002 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.|||Neonatal lethality. A germline-specific conditional knockout produces females that are normal in growth and morphology but display much reduced fecundity in terms of the frequency of successful pregnancy per mating and the litter size. No 5hmC signal is detected in the late male pronuclei of zygotes collected from the conditional knockout females mated with wild-type males. In contrast, deletion of Tet3 from the male germ cells does not seem to affect the change in 5hmC and 5mC.|||Nucleus|||Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG.|||The CXXC-type zinc-finger domain mediates binding to DNA sequences containing unmethylated cytosine or 5-carboxylcytosine in 5'-CCG-3' DNA sequence motifs (PubMed:26774490). It mediates binding to CpG-DNA (By similarity).|||The zinc ions have a structural role. http://togogenome.org/gene/10090:Nhsl2 ^@ http://purl.uniprot.org/uniprot/B1AXH1 ^@ Similarity ^@ Belongs to the NHS family. http://togogenome.org/gene/10090:Nr0b2 ^@ http://purl.uniprot.org/uniprot/Q62227 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine methylation by PRMT5 enhances repression activity of metabolic genes in liver in response to bile acid signaling, by increasing interaction with cofactors.|||Belongs to the nuclear hormone receptor family. NR0 subfamily.|||Cytoplasm|||Expressed in islets of Langerhans (at protein level) (PubMed:14752053). Expressed in a circadian manner in the liver (PubMed:25212631).|||Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (By similarity). Interacts (via N-terminus) with NEUROD1 (via N-terminus and C-terminus) (By similarity). Interacts with ID2 (By similarity). Interacts with NR5A2, PPARA and PPARG (By similarity). Interacts with RARA, RXRA, THRB, NR5A1 and NR1I3 (PubMed:8650544). Interacts with EID1 (PubMed:11964378). Interacts with NR1D1 (PubMed:25212631, PubMed:30555544). Interacts with RORG (PubMed:25212631). Interacts with NFIL3 and BHLHE41 (PubMed:30555544). Interacts with HNF4A; the resulting heterodimer is transcriptionnally inactive (By similarity). Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2/SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (By similarity).|||Mice exhibit a significant disruption in the circadian rhythm of several important hepatic genes involved in the metabolism of lipid, cholesterol, fatty acid and bile acid.|||Nucleus|||Transcriptional regulator that acts as a negative regulator of receptor-dependent signaling pathways (PubMed:8650544). Specifically inhibits transactivation of the nuclear receptor with which it interacts (PubMed:8650544). Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated transcription complex for NEUROD1 (By similarity). Essential component of the liver circadian clock which via its interaction with NR1D1 and RORG regulates NPAS2-mediated hepatic lipid metabolism (PubMed:25212631). Regulates the circadian expression of cytochrome P450 (CYP) enzymes (PubMed:30555544). Represses: NR5A2 and HNF4A to down-regulate CYP2C38, NFLI3 to up-regulate CYP2A5, BHLHE41/HNF1A axis to up-regulate CYP1A2, CYP2E1 and CYP3A11, and NR1D1 to up-regulate CYP2B10, CYP4A10 and CYP4A14 (PubMed:30555544). http://togogenome.org/gene/10090:Dnaaf1 ^@ http://purl.uniprot.org/uniprot/Q9D2H9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DNAAF1 family.|||Cilium-specific protein required for the stability of the ciliary architecture. Plays a role in cytoplasmic preassembly of dynein arms (By similarity). Involved in regulation of microtubule-based cilia and actin-based brush border microvilli (By similarity).|||cilium http://togogenome.org/gene/10090:Samt4 ^@ http://purl.uniprot.org/uniprot/Q9D4X6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Map4k3 ^@ http://purl.uniprot.org/uniprot/A0A3Q4EGQ9|||http://purl.uniprot.org/uniprot/Q99JP0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation (By similarity).|||May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway (By similarity).|||May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. http://togogenome.org/gene/10090:Pum3 ^@ http://purl.uniprot.org/uniprot/Q8BKS9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A 90 degree bend between Pumilio repeats 3 and 4 gives rise to a L-shaped protein.|||Chromosome|||In the adult eye, expressed primarily in retinal ganglion cells and, to a lesser extent, in the pigmented cells.|||Inhibits the poly(ADP-ribosyl)ation activity of PARP1 and the degradation of PARP1 by CASP3 following genotoxic stress. Binds to double-stranded RNA or DNA without sequence specificity. Involved in development of the eye and of primordial germ cells.|||Interacts with PARP1 (via catalytic domain).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Ube2i ^@ http://purl.uniprot.org/uniprot/P63280 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accepts the ubiquitin-like proteins SUMO1, SUMO2 and SUMO3 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2, CBX4 and ZNF451. Can catalyze the formation of poly-SUMO chains. Essential for nuclear architecture, chromosome segregation and embryonic viability. Necessary for sumoylation of FOXL2 and KAT5 (By similarity). Sumoylates p53/TP53 at 'Lys-386'. Mediates sumoylation of ERCC6 which is essential for its transcription-coupled nucleotide excision repair activity (By similarity).|||Belongs to the ubiquitin-conjugating enzyme family.|||Cytoplasm|||Death prior to E7.5 due to major defects in nuclear organization.|||Forms a complex with SENP6 and UBE2I in response to UV irradiation (By similarity). Forms a tight complex with RANGAP1 and RANBP2 (By similarity). Identified in a complex with SUMO2 and UBE2I, where one ZNF451 interacts with one UBE2I and two SUMO2 chains, one bound to the UBE2I active site and the other to another region of the same UBE2I molecule (By similarity). Interacts with SETX (By similarity). Interacts with HIPK1 and HIPK2 (PubMed:10535925). Interacts with PPM1J (PubMed:12633878). Interacts with RASD2 (By similarity). Interacts with TCF3 (PubMed:9409784). Interacts with NR2C1; the interaction promotes its sumoylation (PubMed:17187077). Interacts with SIAH1 (By similarity). Interacts with PARP (By similarity). Interacts with various transcription factors such as TFAP2A, TFAP2B, and TFAP2C (By similarity). Interacts with AR (By similarity). Interacts with ETS1 (By similarity). Interacts with SOX4 (By similarity). Interacts with RWDD3; the interaction enhances the sumoylation of a number of proteins such as HIF1A and I-kappa-B (By similarity). Interacts with FOXL2 (By similarity). Interacts with DNM1l (via its GTPase and B domains); the interaction promotes sumoylation of DNM1L, mainly in its B domain (By similarity). Interacts with NFATC2IP; this inhibits formation of poly-SUMO chains (By similarity). Interacts with FHIT (By similarity). Interacts with PRKRA and p53/TP53 (PubMed:22214662). Interacts with UHRF2 (By similarity). Interacts with NR3C1 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with MTA1 (By similarity). Interacts with ZNF451 (By similarity). Interacts with CPEB3 (PubMed:26074071). Interacts with SUMO1, SUMO2, and SUMO3 (By similarity). Interacts with IPO13 (By similarity). Interacts with DNMT1 (By similarity).|||Nucleus|||Phosphorylation at Ser-71 significantly enhances SUMOylation activity.|||Present in spleen, kidney, lung, brain, heart and testis (at protein level). http://togogenome.org/gene/10090:Tcam1 ^@ http://purl.uniprot.org/uniprot/Q80X70|||http://purl.uniprot.org/uniprot/Q99NB3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. ICAM family.|||Membrane http://togogenome.org/gene/10090:Vmn1r41 ^@ http://purl.uniprot.org/uniprot/A0A0N4SVQ3|||http://purl.uniprot.org/uniprot/Q9EQ44 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Dclk2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YX33|||http://purl.uniprot.org/uniprot/Q6PGN3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 17.5 dpc, predominantly expressed in the central nervous system, throughout the forebrain, midbrain, hindbrain, and the spinal cord. Expressed in the developing neocortex and at low levels in the ventricular zone, especially in the outer neuroblastic layer. In the developing retina, strongly expressed in the postmitotic inner neuroblastic layer. Also found in the developing ovary and, to a lower extent, throughout the kidney.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Binds to and stabilizes microtubules (By similarity). Interacts with MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK9/JNK2, PPP1R9B/NEURABIN-2 and actin.|||Expressed in the central and peripheral nervous system including the brain, spinal cord, cranial and dorsal root ganglia and in the parasympathetic ganglia. Present in neurons, but not in glial cells, in most forebrain areas. Strong expression in the hippocampal CA1 pyramidal cell layer. Expressed in the photoreceptor sensory cilium complex and in eyes. Also detected in individual cells of the olfactory epithelium.|||Frequent spontaneous seizures that originate in the hippocampus, with most animals dying in the first few months of life.|||Protein kinase with a significantly reduced Ca(2+)+/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm.|||The doublecortin domains are involved in the colocalization with microtubules.|||cytoskeleton http://togogenome.org/gene/10090:Nmd3 ^@ http://purl.uniprot.org/uniprot/Q99L48 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit.|||Belongs to the NMD3 family.|||Cytoplasm|||Found in a 60S ribosomal subunit export complex with RAN and XPO1. Interacts with XPO1. Associates with pre-60S ribosomal particles.|||Nucleus http://togogenome.org/gene/10090:Tlk2 ^@ http://purl.uniprot.org/uniprot/O55047 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated; phosphorylation promotes the assembly of higher order oligomers and enzymatic activity.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cell cycle-regulated, with maximal activity in the S-phase. Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase, probably by CHEK1, possibly at Ser-696. This inhibition is cell cycle checkpoint- and ATM-dependent.|||Monomer (By similarity). May form homodimers; homodimerization may enhance autophosphoylation and enzymatic activity (By similarity). Heterodimer with TLK1 (By similarity). Interacts with YWHAZ; association with 14-3-3 proteins such as YWHAZ regulates subcellular location (PubMed:10455159). May also interact with FEZ1/LZTS1 and FEZ2 (By similarity). Interacts with CHD7 and CHD8 (By similarity). Interacts with DYNLL1/LC8 (By similarity).|||Nucleus|||Phosphorylated at Ser-696, probably by CHEK1.|||Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (By similarity). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (By similarity). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (By similarity). Negative regulator of amino acid starvation-induced autophagy (By similarity).|||Testis-specific isoforms may play a role in spermatogenesis. Highly expressed in embryos throughout development.|||Ubiquitously expressed in all tissues examined, with high levels in heart and testis, in particular the pachytene spermatocytes and in round spermatids. Some evidence for the existence of a testis-specific isoform suggesting a role in spermatogenesis.|||cytoskeleton|||nucleoplasm|||perinuclear region http://togogenome.org/gene/10090:Cxcl12 ^@ http://purl.uniprot.org/uniprot/H7BX38|||http://purl.uniprot.org/uniprot/P40224 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (By similarity). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells (By similarity). Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (PubMed:8134392).|||Down-regulated by 12-O-tetradecanoylphorbol 13-acetate (TPA), with 5-fold decrease in expression levels at 1 hour after TPA treatment, 12-fold decrease at 4 hours, undetectable levels after 8 hours and low-level expression returning at 24 hours after treatment. Down-regulated by serum stimulation, with expression levels reaching their minimum at 4 hours after stimulation and returning back to normal levels at 16 hours after stimulation.|||Half of the embryos die by 18.5 dpc, and neonates die within an hour. Mutants display defective B-lymphopoiesis, defective myelopoiesis in the bone marrow but not in the liver, and defective formation of the heart ventricular septum.|||Highest expression levels detected in kidney, liver, spleen and muscle. Isoform Alpha is expressed ubiquitously but at varying levels, while isoform Beta displays tissue-specific expression, with expression detected in kidney, liver, heart, spleen and muscle but not in lung, colon, brain, skin and stomach.|||Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of ACKR3. Interacts with integrin subunit ITGB3 (via the allosteric site (site 2)). Interacts with TNFAIP6 (via Link domain).|||Secreted http://togogenome.org/gene/10090:Syt6 ^@ http://purl.uniprot.org/uniprot/Q9R0N8 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.|||Cell membrane|||Isoform 1 is expressed in the olfactory bulb. Isoform 2 is expressed in the brain (at protein level).|||Isoform 1: Homodimer; disulfide-linked via the cysteine motif (PubMed:10531343, PubMed:10531344). Isoform 1: Can also form heterodimers with SYT3, SYT7, SYT9 and SYT10 (PubMed:10531343, PubMed:10531344, PubMed:10871604). Isoform 1: Interacts with STX1A, STX1B and STX2; the interaction is Ca(2+)-dependent (PubMed:15774481). Isoform 2: Is not able to form homodimer and heterodimers (PubMed:10531344).|||May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis (By similarity). May mediate Ca(2+)-regulation of exocytosis in acrosomal reaction in sperm (PubMed:15774481).|||Membrane|||The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds.|||cytosol|||synaptic vesicle membrane http://togogenome.org/gene/10090:Traf5 ^@ http://purl.uniprot.org/uniprot/P70191|||http://purl.uniprot.org/uniprot/Q3UMS9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR.|||Belongs to the TNF receptor-associated factor family.|||Belongs to the TNF receptor-associated factor family. A subfamily.|||Cytoplasm|||Homotrimer (Probable). Heterotrimer with TRAF3 (By similarity). Associates with TNFRSF5/CD40 through interaction with TRAF3 (By similarity). Associates with LTBR/TNFRSF3, TNFRSF4, TNFRSF8/CD30, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF17, TNFRSF19/TROY, RIPK2, MAP3K14, MAP3K5, and TRAF and TNF receptor associated protein TDP2 (By similarity). Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain) (By similarity).|||The MATH/TRAF domain binds to receptor cytoplasmic domains.|||Ubiquitinated at Lys-318 by the SCF(FBXL2) complex, leading to its degradation by the proteasome.|||cytosol http://togogenome.org/gene/10090:Cep112 ^@ http://purl.uniprot.org/uniprot/Q5PR68 ^@ Subcellular Location Annotation ^@ centrosome http://togogenome.org/gene/10090:Trmt13 ^@ http://purl.uniprot.org/uniprot/Q8BYH3 ^@ Function|||Similarity ^@ Belongs to the methyltransferase TRM13 family.|||tRNA methylase which 2'-O-methylates cytidine(4) in tRNA(Pro) and tRNA(Gly)(GCC), and adenosine(4) in tRNA(His). http://togogenome.org/gene/10090:Trim41 ^@ http://purl.uniprot.org/uniprot/Q5NCC3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||Deletion mutant impairs the production of inflammatory cytokines and type I interferons in macrophages after infection with both DNA and RNA viruses.|||E3 ligase that plays essential roles in innate antiviral response (PubMed:33640899). Directly binds to influenza A virus or vesicular stomatitis virus nucleoproteins and targets them for ubiquitination and proteasomal degradation, thereby limiting viral infections (By similarity). Activates the innate antiviral response by catalyzing monoubiquitination of CGAS, thereby activating CGAS (By similarity). Also involved in innate antiviral response by mediating 'Lys-63'-linked polyubiquitylation of BCL10 which in turn hubs NEMO for activation of NF-kappa-B and IRF3 pathways (PubMed:33640899). Catalyzes the ubiquitin-mediated degradation of other substrates including protein kinase C, ZSCAN21 or TOP3B suggesting additional roles besides its function in immune response (PubMed:30485814).|||Interacts with PRKCA. Interacts with NOD2 (By similarity). Interacts with TRIM17; this interaction prevents TRIM41 activity on ZSCAN2 (PubMed:30485814).|||Nucleus http://togogenome.org/gene/10090:Pym1 ^@ http://purl.uniprot.org/uniprot/Q8CHP5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pym family.|||Cytoplasm|||Interacts (via N-terminus) with MAGOH and RBM8A; the interaction is direct. Associates (eIF2A-like region) with the 40S ribosomal subunit and the 48S preinitiation complex (By similarity).|||Key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation. Acts as an EJC disassembly factor, allowing translation-dependent EJC removal and recycling by disrupting mature EJC from spliced mRNAs. Its association with the 40S ribosomal subunit probably prevents a translation-independent disassembly of the EJC from spliced mRNAs, by restricting its activity to mRNAs that have been translated. Interferes with NMD and enhances translation of spliced mRNAs, probably by antagonizing EJC functions (By similarity).|||The eIF2A-like region shares sequence similarity with eIF2A and mediates the interaction with the 40S ribosomal subunit and the 48S preinitiation complex.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Or2y10 ^@ http://purl.uniprot.org/uniprot/Q7TQT5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Samt2 ^@ http://purl.uniprot.org/uniprot/Q497M0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Trim36 ^@ http://purl.uniprot.org/uniprot/E9Q3A0|||http://purl.uniprot.org/uniprot/Q80WG7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:19232519). Involved in chromosome segregation and cell cycle regulation (PubMed:19232519). May play a role in the acrosome reaction and fertilization (PubMed:12917430).|||Expressed in testis (PubMed:12917430). Strongly expressed in the neural tube region in 14.5 dpc embryos (PubMed:28087737).|||Expressed only in testicular germ cells after meiotic division. Expression was first detected at the age of 4 weeks.|||Interacts with CENPH.|||acrosome|||cytoskeleton http://togogenome.org/gene/10090:Etnk1 ^@ http://purl.uniprot.org/uniprot/Q9D4V0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the choline/ethanolamine kinase family.|||Cytoplasm|||Highly specific for ethanolamine phosphorylation. May be a rate-controlling step in phosphatidylethanolamine biosynthesis. http://togogenome.org/gene/10090:Ints9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J5|||http://purl.uniprot.org/uniprot/Q8K114 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although strongly related to RNA-specific endonuclease proteins, it lacks the HXHXDH motif that binds zinc and participates in the catalytic center. Its function as endonuclease is therefore unsure.|||Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS9 subfamily.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12 (By similarity). Interacts with ESRRB, ESRRB is probably not a core component of the multiprotein complex Integrator and this association is a bridge for the interaction with the multiprotein complex Integrator; attracts the transcriptional machinery (PubMed:26206133).|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Nucleus http://togogenome.org/gene/10090:Pigp ^@ http://purl.uniprot.org/uniprot/B8JK65|||http://purl.uniprot.org/uniprot/B8JK66|||http://purl.uniprot.org/uniprot/B8JK67|||http://purl.uniprot.org/uniprot/Q9JHG1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIGP family.|||Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts directly with PIGA and PIGQ.|||Expressed in tongue.|||Membrane|||Part of the complex catalyzing the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, the first step of GPI biosynthesis.|||Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. http://togogenome.org/gene/10090:Ccl12 ^@ http://purl.uniprot.org/uniprot/Q545B5|||http://purl.uniprot.org/uniprot/Q62401 ^@ Function|||Induction|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||By interferon gamma and lipopolysaccharides (LPS).|||Chemotactic factor that attracts eosinophils, monocytes, and lymphocytes but not neutrophils. Potent monocyte active chemokine that signals through CCR2. Involved in allergic inflammation and the host response to pathogens and may play a pivotal role during early stages of allergic lung inflammation.|||Homodimer.|||Predominantly expressed in the lymph nodes and thymus. Also found in the salivary glands containing lymph nodes, breast, heart, lung, brain, small intestine, kidney and colon.|||Secreted|||The polymorphism in strain SJL/J may be associated with severity of clinical symptoms of experimental allergic encephalomyelitis, an animal model of multiple sclerosis, and susceptibility to the monophasic remitting/nonrelapsing form of the disease. http://togogenome.org/gene/10090:Tbc1d32 ^@ http://purl.uniprot.org/uniprot/Q3URV1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CDK20, which promotes CDK20 stability and function (PubMed:20159594). Interacts with FAM149B1; may play a role in cilium assembly.|||Mice exhibit exencephaly, poorly developed eyes and preaxial polydactyly, due to defects in ventral patterning.|||Present at 10.5 dpc (at protein level).|||Required for high-level Shh responses in the developing neural tube. Together with CDK20, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing GLI2 to be properly activated in response to Shh signaling.|||The Rab-GAP TBC domain appears to be inactive, probably due to a lack of the essential Arg and Gln in the catalytic finger motifs.|||cilium http://togogenome.org/gene/10090:Map7d3 ^@ http://purl.uniprot.org/uniprot/A2AEY4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MAP7 family.|||High expression in lung, skeletal muscle, brain, and kidney, with much weaker expression in spleen, small intestine, liver, and heart.|||Promotes the assembly and stability of microtubules.|||spindle http://togogenome.org/gene/10090:Kcnj6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J239|||http://purl.uniprot.org/uniprot/A0A338P6L0|||http://purl.uniprot.org/uniprot/P48542|||http://purl.uniprot.org/uniprot/Q0VB45|||http://purl.uniprot.org/uniprot/Q8C4T8|||http://purl.uniprot.org/uniprot/Q8C8Y6 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ6 subfamily.|||Cerebellum, testes, cortex and substentia nigra.|||Defects in Kcnj6 are the cause of the weaver (wv) phenotype. Homozygous animals suffer from severe ataxia that is obvious by about the second postnatal week. The cerebellum of these animals is drastically reduced in size due to depletion of the major cell type of cerebellum, the granule cell neuron. Heterozygous animals are not ataxic but have an intermediate number of surviving granule cells. Male homozygotes are sterile, because of complete failure of sperm production. Both hetero- and homozygous animals undergo sporadic tonic-clonic seizures.|||May associate with GIRK1 or GIRK4 to form a G-protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane (By similarity).|||Membrane|||This potassium channel is controlled by G proteins. It plays a role in granule cell differentiation, possibly via membrane hyperpolarization. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. http://togogenome.org/gene/10090:Nr2c2 ^@ http://purl.uniprot.org/uniprot/G3X9W4|||http://purl.uniprot.org/uniprot/P49117|||http://purl.uniprot.org/uniprot/Q3ZAS1 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Expressed, during embryogenesis, in perichondrium, developing glomeruli structures and tubules of kidney, as well as in intestiinal villi. Also expressed in lung and hair follicles.|||Homodimer; can bind DNA as homodimer (By similarity). Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity (By similarity). Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain (PubMed:16887930). Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity (PubMed:16887930). Interacts with NLRP10. Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression (By similarity).|||Impaired spermatogenesis. Mutant animals have smaller cerebellums with disruption of lobes VI-VII. They exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells 7 days after birth. Deficiencies in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Also responses to novel environmental situations are inhibited. NR2C1 and NR2C2 double knockout results in embryonic lethality around 7.5 dpc and increased apoptosis.|||Induced by retinoic acid.|||Nucleus|||Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Activates transcriptional activity of LHCG and is antagonist of PPARA-mediated transactivation (By similarity). Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior.|||Phosphorylation on Ser-19 and Ser-68 is an important regulator of NR2C2-mediated transcriptional activity. Phosphorylation on these residues recruits the corepressor, NRIP1, leading to transcripional repression, whereas the non-phosphorylated form preferentially recruits the coactivator, PCAF. http://togogenome.org/gene/10090:Med15 ^@ http://purl.uniprot.org/uniprot/A0A338P730|||http://purl.uniprot.org/uniprot/E9Q7C1|||http://purl.uniprot.org/uniprot/Q3TE00|||http://purl.uniprot.org/uniprot/Q6KAM1|||http://purl.uniprot.org/uniprot/Q924H2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 9.5 dpc ubiquitously expressed at low levels with slightly elevated levels in the pharyngeal arches and in the forelimb buds. At 10.5 dpc expression was more pronounced in the first and second pharyngeal arches, the nasal processes and the limb buds. At 11.5 dpc expression is high in frontonasal region, maxillary and mandibular processes of the first and second pharyngeal arch and developing fore and hindlimbs. From 11.5 dpc-12.5 dpc expression is seen in the distal parts of the developing limbs and in the facial region. At 12.5 dpc transcripts were found in the developing hair follicles of the vibrissae.|||Belongs to the Mediator complex subunit 15 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with SMAD2, SMAD3, SREBF1 and SREBF2. Interacts with WWTR1 (By similarity). Interacts with TRIM11 (By similarity).|||Cytoplasm|||Nucleus|||Ubiquitinated by TRIM11, leading to proteasomal degradation. http://togogenome.org/gene/10090:Foxi3 ^@ http://purl.uniprot.org/uniprot/D3Z120 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Embryonic lethality due to impaired pharyngeal arches segmentation (PubMed:24650709). Embryos fail to form endodermal pouches and this results in failed pharyngeal arches segmentation leading to severe defects in the skull, jaw, and ears (PubMed:24650709, PubMed:26550799). Craniofacial neural crest cells undergo apoptosis in the mutant embryos at 10.0 day post coitum (dpc) (PubMed:24650709). Conditional deletion in epithelium leads to fusion of molars with abnormally patterned shallow cusps (PubMed:26450968). Conditional deletion impairs postnatal hair growth and hair cycling, resulting in poor hair regeneration upon hair plucking; defects are caused by progressive depletion of hair follicle stem cells (PubMed:26992132). Conditional deletion also results in defects in the distal pharyngeal apparatus (PubMed:31412026).|||Nucleus|||Phosphorylation promotes the transcription factor activity (PubMed:30467319). Dephosphorylation by protein phosphatase 2A (PP2A) reduces its activity (PubMed:30467319).|||Regulated by ectodysplasin (EDA) in skin appendage placodes.|||Specifically expressed in the epithelium in developing ectodermal appendages (PubMed:23441037). Expressed in pharyngeal endoderm and ectoderm (PubMed:24650709). Expressed in pre-placodal ectoderm (PubMed:26550799). Down-regulated as the otic placode is induced (PubMed:26550799). Expressed in teeth and hair follicles throughout embryogenesis (PubMed:23441037). Expressed in mammary glands only during the earliest stages of development (PubMed:23441037).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor required for pharyngeal arch development, which is involved in hair, ear, jaw and dental development (PubMed:24650709, PubMed:26550799, PubMed:26992132, PubMed:30467319). May act as a pioneer transcription factor during pharyngeal arch development (PubMed:26550799, PubMed:26992132). Required for epithelial cell differentiation within the epidermis (PubMed:26450968). Acts at multiple stages of otic placode induction: necessary for preplacodal ectoderm to execute an inner ear program (PubMed:26550799). Required for hair follicle stem cell specification (PubMed:26992132). Acts downstream of TBX1 for the formation of the thymus and parathyroid glands from the third pharyngeal pouch (PubMed:31412026). http://togogenome.org/gene/10090:Gjb1 ^@ http://purl.uniprot.org/uniprot/A0A654IEJ3|||http://purl.uniprot.org/uniprot/P28230 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins. Interacts with CNST.|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Membrane|||Mice lacking both Gja12 and Gjb1 display a severe demyelination phenotype associated with oligodendrocyte death. These mice develop action tremors, tonic seizures, sporadic convulsions and loss of consciousness preceding death in the sixth week after birth.|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Cbx2 ^@ http://purl.uniprot.org/uniprot/P30658 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of a PRC1-like complex (By similarity). The composition of the PRC1 complex may differ between the PRC1 complex in pluripotent embryonic stem cells containing RNF2, CBX7 and PCGF2, and the PRC1 complex in differentiating cells containing RNF2, CBX2, CBX4 and BMI1 (PubMed:22226355). Interacts with RING1/RNF2 (PubMed:9312051, PubMed:22226355). Interacts (via chromodomain) with histone H3K9Me3 and H3K27me3 (PubMed:16537902). May interact with H3C15 and H3C1 (By similarity).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (By similarity). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (By similarity). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) or at 'Lys-27' (H3K27me3) (PubMed:16537902). Plays a role in the lineage differentiation of the germ layers in embryonic development (PubMed:22226355). Involved in sexual development, acting as activator of NR5A1 expression (By similarity).|||Expressed in embryoid bodies.|||Expressed in most embryonic tissues except the heart from 8.5 to 11.5 dpc. Expressed in central nervous system (CNS, ventricular zone and spinal cord), peripheral nervous system (PNS, sensory cranial and spinal ganglia), olfactory and tongue epithelia, lung, gastrointestinal duct and urogenital system at 13.5 dpc. Expressed in CNS, thymus, various epithelial cell types including the olfactory, tooth and tongue epithelia at 15.5 dpc.|||Nucleus speckle http://togogenome.org/gene/10090:Kpna1 ^@ http://purl.uniprot.org/uniprot/Q60960 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the importin alpha family.|||Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.|||Cytoplasm|||Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.|||Heterodimer; with KPNB1 (By similarity). Interacts with NSMF; the interaction occurs in a calcium-independent manner after synaptic NMDA receptor stimulation and is required for nuclear import of NSMF but is competed by CABP1 (By similarity). Interacts with APEX1 (via its N-terminus) (By similarity). Interacts with CTNNBL1 (via its N-terminal) (By similarity). Interacts with AICDA (via its NLS) (By similarity). Interacts with ANP32E (PubMed:10692581). Interacts with ZIC3 (PubMed:18716025). Interacts with SNAI1 (via zinc fingers) (By similarity). Interacts with DCAF8 (By similarity). Interacts with ITSN1 isoform 2 (PubMed:29599122). Interacts with TALDO1 isoform 1 (PubMed:27703206).|||Low levels in all tissues examined.|||Nucleus|||Polyubiquitinated in the presence of RAG1 (in vitro).|||The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity).|||The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity). http://togogenome.org/gene/10090:Pnkd ^@ http://purl.uniprot.org/uniprot/Q69ZP3 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||By Hepatitis C virus core protein.|||Cytoplasm|||Expressed in many discrete areas of the brain.|||Isoform 2 interacts with the sarcomeric proteins, MRLC2, MYOM1 and ENO3.|||Membrane|||Mice overexpressing Pnkd infused with angiotensin II develop greater cardiac hypertrophy as well as increased cardiac inflammation and fibrosis, compared with angiotensin II-infused normal mice. In these mice, Pnkd overexpression promote nuclear factor kappa B activation.|||Mitochondrion|||Nucleus|||Probable hydrolase that plays an aggravative role in the development of cardiac hypertrophy via activation of the NF-kappa-B signaling pathway. http://togogenome.org/gene/10090:Pcgf5 ^@ http://purl.uniprot.org/uniprot/Q3UK78 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Combined disruption of both Pcgf3 and Pcgf5 causes embryonic lethality; there are no live progeny. Male embryos are detected at 9.5 and 10.5 dpc, but are smaller than normal. Female embryos are already extensively degraded at 9.5 dpc. Placentas from male embryos have some parietal trophoblast giant cells, but fail to form a labyrinth. Placentas from female embryos lack trophoblasts altogether and fail to form a labyrinth. Defects can be attributed to the observed lack of monoubiquitination of histone H2A 'Lys-119' and lack of Xist-mediated silencing of one copy of the X chromosome.|||Component of a PRC1-like complex that contains PCGF5, RNF2 and UBE2D3 (PubMed:28596365). Interacts with RNF2; the interaction is direct (PubMed:27136092, PubMed:28596365). Interacts with CBX6, CBX7 and CBX8. Interacts with AUTS2; the interaction is direct. Identified in a complex that contains AUTS2, PCGF5, CSNK2B and RNF2 (By similarity).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:27136092, PubMed:28596365). Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity (By similarity). Plays a redundant role with PCGF3 as part of a PRC1-like complex that mediates monoubiquitination of histone H2A 'Lys-119' on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females (PubMed:28596365).|||Detected in hematopoietic stem cells and multipotent progenitor cells.|||Nucleus|||Selective knockout in hematopoietic stem cells has only minor effects on gene expression and hematopoiesis, probably due to functional compensation by Pcgf1.|||nucleoplasm http://togogenome.org/gene/10090:Hykk ^@ http://purl.uniprot.org/uniprot/Q5U5V2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the aminoglycoside phosphotransferase family.|||Catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine.|||Cytoplasm http://togogenome.org/gene/10090:Cdx1 ^@ http://purl.uniprot.org/uniprot/P18111 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Caudal homeobox family.|||Intestinal epithelium.|||Nucleus|||Plays a role in transcriptional regulation. Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells. Binds to the PRKD1 promoter in colorectal cancer (CRC) cells. Could play a role in the terminal differentiation of the intestine. Binds preferentially to methylated DNA. http://togogenome.org/gene/10090:Lyzl6 ^@ http://purl.uniprot.org/uniprot/A0A077S2U3|||http://purl.uniprot.org/uniprot/Q9DA11 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 22 family.|||Cell surface|||Expressed strongly in testis and epididymis and weakly in seminal vesicle, vas deferens, kidney and spleen (PubMed:24013621). Highly expressed in primary spermatocytes and round spermatids (at protein level) (PubMed:24013621).|||In testis expressed from day 21 during postnatal development (PubMed:24013621). In the epidydimis, first detected at day 28 and high expression is maintained until day 35. Thereafter, level declines gradually (PubMed:24013621).|||May be involved sperm-egg plasma membrane adhesion and fusion during fertilization. Exhibits bacteriolytic activity in vitro against Micrococcus luteus and Staphylococcus aureus. Shows weak bacteriolytic activity against Gram-positive bacteria at physiological pH. Bacteriolytic activity is pH-dependent, with a maximum at around pH 5.6 (By similarity).|||Monomer.|||Secreted|||flagellum http://togogenome.org/gene/10090:Guca2b ^@ http://purl.uniprot.org/uniprot/O09051|||http://purl.uniprot.org/uniprot/Q9QUQ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the guanylin family.|||Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins. May be a potent physiological regulator of intestinal fluid and electrolyte transport. May be an autocrine/paracrine regulator of intestinal salt and water transport (By similarity).|||Localized predominantly in intestinal villi and the corticomedullary junction of the kidney.|||Secreted http://togogenome.org/gene/10090:Or5b97 ^@ http://purl.uniprot.org/uniprot/Q8VFX3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:F8a ^@ http://purl.uniprot.org/uniprot/Q00558 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Early endosome|||Interacts with HTT (via C-terminus) (PubMed:11035034). Interacts with RAB5A (By similarity). Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A onto early endosomes (By similarity).|||Nucleus|||Produced abundantly in a wide variety of cell types.|||RAB5A effector molecule that is involved in vesicular trafficking of early endosomes. Mediates the recruitment of HTT by RAB5A onto early endosomes (By similarity). The HTT-F8A1/F8A2/F8A3-RAB5A complex stimulates early endosomal interaction with actin filaments and inhibits interaction with microtubules, leading to the reduction of endosome motility (PubMed:16476778).|||nuclear body http://togogenome.org/gene/10090:Fam220a ^@ http://purl.uniprot.org/uniprot/Q3ZN08 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Interacts with STAT3.|||May negatively regulate STAT3.|||Nucleus http://togogenome.org/gene/10090:Or5p5 ^@ http://purl.uniprot.org/uniprot/Q7TRV2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zkscan3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1L3|||http://purl.uniprot.org/uniprot/Q91VW9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Cytoplasm|||Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Nucleus|||Transcriptional factor that binds to the consensus sequence 5'-[GT][AG][AGT]GGGG-3' and acts as a repressor of autophagy. Specifically represses expression of genes involved in autophagy and lysosome biogenesis/function such as MAP1LC3B, ULK1 or WIPI2. Associates with chromatin at the ITGB4 and VEGF promoters (By similarity). http://togogenome.org/gene/10090:Rptn ^@ http://purl.uniprot.org/uniprot/P97347 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the S100-fused protein family.|||Can be divided into a N-terminal domain with significant homology to S100-like calcium-binding proteins, a central domain containing a series of short tandem repeats, and two flanking segments with low homology to the consensus sequences of the central repeats.|||Detectable in the stratified internal epithelia of forestomach and tongue and to a lesser degree in normal skin epidermis, where it is restricted to the differentiated suprabasal cell layers. Overexpressed in skin tumors.|||Expressed during late differentiation of the epidermis.|||Involved in the cornified cell envelope formation. Multifunctional epidermal matrix protein.|||Potential substrate of transglutaminase. Some arginines are probably converted to citrullines by peptidylarginine deimidase.|||extracellular matrix http://togogenome.org/gene/10090:Bmal2 ^@ http://purl.uniprot.org/uniprot/Q2VPD4 ^@ Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with CLOCK to form the BMAL2-CLOCK transactivator. Can form heterodimers or homodimers which interact directly with CLOCK to form the transcription activator. Interacts with NPAS2 and HIF1A (By similarity). Interacts with PER2.|||Constitutively expressed in the SCN. Little change throughout day under dark/light cycle.|||Expressed in the suprachiasmatic nucleus (SCN).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. http://togogenome.org/gene/10090:Rhox4b ^@ http://purl.uniprot.org/uniprot/Q9JI43 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sfrp2 ^@ http://purl.uniprot.org/uniprot/P97299|||http://purl.uniprot.org/uniprot/Q3UI35 ^@ Caution|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the secreted frizzled-related protein (sFRP) family.|||During kidney development, expressed at 10.5 dpc in the mesonephric tubules, and at 12.5 dpc strongly expressed in the comma shaped bodies and surrounding ureter stalk. In 14.5 dpc kidney, expressed in the S-shaped bodies. In the developing nervous system, expressed in the presumptive hindbrain and the ventral part of the neural tube from 8.0 dpc onwards. At 9.5 dpc, expression is additionally detected in the mesonephros and the optic vesicle. 10 dpc expression is found in the second and third branchial cleft, in the eye, the ventral neural tube and specific rhombomeres and prosomers. 10.5 dpc brain shows specific expression in the basal and alar plate. In developing eye, expressed at 9.0 dpc in the optic placode, and at 9.5 dpc in the optic vesicle. By 10.5 dpc, expression found in the lens vesicle and the inner layer of the invaginating optic vesicle. Strong expression at 14.5 dpc in the anterior lens epithelium, decreasing thereafter. Expression also found in the prospective neural retina. In developing limbs, expression found at 11.5 dpc in the shoulder and at the distal end of the cartilaginous condensation. At 12.5 dpc, expressed in the foot and hand paddle extending along the digital rays. Expressed, at 13.5 dpc and 14.5 dpc, in the forelimb and hindlimb where the interphalangeal joints will develop. Also expressed at 14.5 dpc between the sternal bands and where the ribs contact the sternum. In other developing structures, expression found at 11.5 dpc, in the maxillary and mandibular component of the first branchial arch, and later, in the loose mesenchyme surrounding cartilage and epithelia of the skull as well as in the whisker follicles. Expressed in the oral mesenchyme lingual to the developing mandibular tooth buds at 13.5 dpc (PubMed:27713059). Expressed in developing teeth, with the highest levels at 15.5 dpc and 16.5 dpc in the mesenchyme and the dental epithelium of the developing molars. Expressed in development smooth muscle surrounding the esophagus at 11.5 dpc, the dorsal aorta and the ductus arteriosus at 14.5 dpc, and the ureter stalk at 15.5 dpc.|||Highly expressed in the eye. Weaker expression in heart and lung.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP2 may be important for eye retinal development and for myogenesis.|||The FZ domain is involved in binding with Wnt ligands. http://togogenome.org/gene/10090:Myd88 ^@ http://purl.uniprot.org/uniprot/P22366|||http://purl.uniprot.org/uniprot/Q3U7M4 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:9697844). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9575168, PubMed:9697844). Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway (PubMed:9697844). Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes (PubMed:17018642). Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA) derived from viruses, induces IL1B release through NLRP3 inflammasome activation (By similarity). MyD88-mediated signaling in intestinal epithelial cells is crucial for maintenance of gut homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine (PubMed:17635956, PubMed:21998396). Mediates leukocyte recruitment at the inflammatory site (PubMed:18941239).|||Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response.|||By interleukin-6.|||Cytoplasm|||Defective in its ability to induce IRAK phosphorylation and NF-kappa-B activation and can function as a negative regulator of activation by IL-1 or lipopolysaccharide (LPS).|||Detected in bone marrow. Isoform 1 is expressed in testis, kidney, lung, ovary, adrenal gland, provstate, thymus and heart, and weakly in skeletal muscle, liver, spleen and brain. Isoform 2 is mainly expressed in the spleen and weakly in brain.|||Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR4, IRAK1, IRAK2 and IRAK4 via their respective TIR domains.|||Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR4, IRAK1, IRAK2 and IRAK4 via their respective TIR domains. Interacts with IL18R1. Interacts with BMX, IL1RL1, IKBKE and IRF7. Interacts with LRRFIP1 and LRRFIP2; this interaction positively regulates Toll-like receptor (TLR) signaling in response to agonist. Interacts with FLII. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-binding. Interacts with IRF1. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and TRAF6; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. May interact with PIK3AP1. Interacts (via TIR domain) with DHX9 (via H2A and OB-fold regions); this interaction is direct. Interacts with OTUD4 deubiquitinase; the interaction is direct (PubMed:29395066).|||Major isoform.|||Mice appear normal, but display loss of activation of NF-kappa-B in response to IL-1 or IL-18. They show no increase in interferon gamma production or in stimulation of natural killer cell activity in response to IL-18. They are impaired in production of cytokines in response to IL-1. They have defects in pro-inflammatory gene expression and leukocyte recruitment after brain injury. Mice have a diminished capacity to kill L.monocytogenes in the lumen of the distal small intestine and express markedly diminished levels of REG3G.|||Nucleus|||The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.|||Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4 specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88. http://togogenome.org/gene/10090:Or6c3 ^@ http://purl.uniprot.org/uniprot/Q8VFI0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cox7c ^@ http://purl.uniprot.org/uniprot/P17665 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIIc family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Interacts with RAB5IF (By similarity).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Hgs ^@ http://purl.uniprot.org/uniprot/Q3UMA3|||http://purl.uniprot.org/uniprot/Q99LI8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Part of a complex at least composed of HSG, STAM2 (or probably STAM) and EPS15 (By similarity). Interacts with STAM (PubMed:9407053, PubMed:19278655). Interacts with STAM2 (PubMed:10651905). Interacts with EPS15; the interaction is direct, calcium-dependent and inhibited by SNAP25 (By similarity). Identified in a complex with STAM and LITAF (By similarity). Found in a complex with STAM and E3 ligase ITCH and DTX3L (By similarity). Interacts with E3 ligase DTX3L; the interaction brings together STAM and HSG, promotes their recruitment to early endosomes and decreases STAM and HGS ubiquitination by ITCH (By similarity). Interacts with NF2; the interaction is direct (By similarity). Interacts with ubiquitin; the interaction is direct (PubMed:11988743). Interacts with VPS37C (By similarity). Interacts with SMAD1, SMAD2 and SMAD3 (PubMed:11094085). Interacts with TSG101; the interaction mediates the association with the ESCRT-I complex (PubMed:12802020). Interacts with SNAP25; the interaction is direct and decreases with addition of increasing concentrations of free calcium (By similarity). Interacts with SNX1; the interaction is direct (By similarity). Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR (By similarity). Interacts with TRAK1 (By similarity). Interacts with TRAK2 (By similarity). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (By similarity). Interacts with ARRDC3 (By similarity). Identified in a complex containing at least ARRDC4, AVPR2 and HGS (By similarity). Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain) (PubMed:16159959). Interacts with LAPTM4B; promotes HGS ubiquitination (By similarity).|||Cytoplasm|||Early endosome membrane|||Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix.|||Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation.|||Mice show a defect in ventral folding morphogenesis, exhibiting two bilateral heart tubes and absence of foregut, and died around embryonic day 11. Significantly enlarged endosomes were also detected in cells of the endoderm.|||Phosphorylated on Tyr-334. This phosphorylation occurs in response to EGF. A minor site of phosphorylation on Tyr-329 is detected. Protein phosphorylation may also be triggered in response to IL-2, GM-CSF and HGF.|||The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions (By similarity).|||Ubiquitinated by ITCH.|||Ubiquitous expression in adult and fetal tissues with higher expression in testis.|||multivesicular body membrane http://togogenome.org/gene/10090:Cep295 ^@ http://purl.uniprot.org/uniprot/Q8BQ48 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Centriole-enriched microtubule-binding protein involved in centriole biogenesis. Essential for the generation of the distal portion of new-born centrioles in a CENPJ- and CEP120-mediated elongation dependent manner during the cell cycle S/G2 phase after formation of the initiating cartwheel structure. Required for the recruitment of centriolar proteins, such as POC1B, POC5 and CEP135, into the distal portion of centrioles. Also required for centriole-to-centrosome conversion during mitotic progression, but is dispensable for cartwheel removal or centriole disengagement. Binds to and stabilizes centriolar microtubule.|||Interacts (via ALMS motif) with microtubules; this interaction is direct.|||The N-terminal and the ALMS motif-containing C-terminal regions are essential for CEP295-mediated centriole elongation.|||centriole|||centrosome|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Rptor ^@ http://purl.uniprot.org/uniprot/A2ACM0|||http://purl.uniprot.org/uniprot/A4FUW1 ^@ Similarity ^@ Belongs to the WD repeat RAPTOR family. http://togogenome.org/gene/10090:Boll ^@ http://purl.uniprot.org/uniprot/Q924M5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM DAZ family.|||Cytoplasm|||First expressed in stage III spermatocytes and peaks in late pachytene or diplotene stage spermatocytes. Expressed in secondary spermatocytes and early spermatids, then decreases until it is undetectable in spermatids.|||Interacts with DAZ1 and DAZL.|||Probable RNA-binding protein, which may be required during spermatogenesis. May act by binding to the 3'-UTR of mRNAs and regulating their translation (By similarity).|||Testis specific. Not expressed in early embryos, primoridal germ cells and spermatogonial cells. First expressed in the cytoplasm of spermatocytes and then persists through meiosis. http://togogenome.org/gene/10090:Ttc14 ^@ http://purl.uniprot.org/uniprot/Q9CSP9 ^@ Miscellaneous|||Similarity ^@ Belongs to the TTC14 family.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Ucn2 ^@ http://purl.uniprot.org/uniprot/Q99ML8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.|||Binds with high affinity to CRF receptors 2-alpha and 2-beta.|||Glycosylated.|||Secreted|||Suppresses food intake, delays gastric emptying and decreases heat-induced edema. Might represent an endogenous ligand for maintaining homeostasis after stress (By similarity). http://togogenome.org/gene/10090:Fkbpl ^@ http://purl.uniprot.org/uniprot/O35450 ^@ Function|||Subunit ^@ Forms a ternary complex with CDKN1A/p21 and HSP90AB1/Hsp90.|||May be involved in response to X-ray. Regulates p21 protein stability by binding to Hsp90 and p21. http://togogenome.org/gene/10090:Gcgr ^@ http://purl.uniprot.org/uniprot/Q3UN81|||http://purl.uniprot.org/uniprot/Q61606 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Expressed predominantly in liver, kidney, adrenal, lung and stomach, while lower levels of expression are detected in brown and white adipose tissue, cerebellum, duodenum and heart.|||G-protein coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system.|||Ligand-binding promotes phosphorylation of serine residues in the C-terminal cytoplasmic domain. Phosphorylation is important for receptor endocytosis after ligand-binding (By similarity).|||Membrane|||Mice are born at the expected Mendelian rate. They display pancreas islet and alpha-cell hyperplasia and increased glucagon levels, but normal insulin levels. Mice display low blood glucose levels combined with increased hepatic glycogen levels. They develop severe hypoglycemia after prolonged fasting. Mutant mice are fertile, but the females produce only few pups; half of the embryos die before birth, and liveborn pups do not survive more than one day. These pups are much smaller than their littermates and exhibit severe hypoglycemia. http://togogenome.org/gene/10090:Tmem91 ^@ http://purl.uniprot.org/uniprot/D3Z7E7|||http://purl.uniprot.org/uniprot/D3Z7E8|||http://purl.uniprot.org/uniprot/Q8C581 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CD225/Dispanin family.|||Membrane http://togogenome.org/gene/10090:Ptpn1 ^@ http://purl.uniprot.org/uniprot/P35821|||http://purl.uniprot.org/uniprot/Q3TZW9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.|||Endoplasmic reticulum membrane|||Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts with MET.|||Most abundant in testis. Also found in kidney, spleen, muscle, liver, heart and brain.|||S-nitrosylation of Cys-215 inactivates the enzyme activity.|||Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50 (By similarity).|||Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.|||Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET (By similarity). http://togogenome.org/gene/10090:Glrx5 ^@ http://purl.uniprot.org/uniprot/Q80Y14 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutaredoxin family. Monothiol subfamily.|||Detected in bone, liver, muscle and kidney.|||Homodimer. Interacts with ISCU. Interacts with BOLA1.|||Mitochondrion matrix|||Monothiol glutaredoxin involved in mitochondrial iron-sulfur (Fe/S) cluster transfer (PubMed:19442627). Receives 2Fe/2S clusters from scaffold protein ISCU and mediates their transfer to apoproteins, to the 4Fe/FS cluster biosynthesis machinery, or export from mitochondrion (By similarity). Required for normal regulation of hemoglobin synthesis by the iron-sulfur protein ACO1 (By similarity).|||Ubiquitously expressed at 7.5 dpc. At 8.5 dpc, preferential expression in yolk sac blood islands. Progressive down-regulation in maturing primitive red cells between 10.5 and 12.5 dpc. High expression in fetal liver at 12.5 dpc. http://togogenome.org/gene/10090:Rbm38 ^@ http://purl.uniprot.org/uniprot/Q62176 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RBM38 family.|||Expressed in cardiac and skeletal muscle tissues.|||It is uncertain whether Met-1 or Met-22 is the initiator.|||Nucleus|||RNA-binding protein that specifically bind the 3'-UTR of CDKN1A transcripts, leading to maintain the stability of CDKN1A transcripts, thereby acting as a mediator of the p53/TP53 family to regulate CDKN1A. CDKN1A is a cyclin-dependent kinase inhibitor transcriptionally regulated by the p53/TP53 family to induce cell cycle arrest. Has the ability to induce cell cycle arrest in G1 and maintain the stability of CDKN1A transcripts induced by p53/TP53. Also acts as a mRNA splicing factor. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2 (By similarity). Plays a role in myogenic differentiation.|||cytosol http://togogenome.org/gene/10090:Gm20833 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXX7 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Purg ^@ http://purl.uniprot.org/uniprot/Q8R4E6 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PUR DNA-binding protein family.|||Isoform 1 is expressed in testis. Isoform 2 is expressed in blastocyst and kidney.|||Nucleus http://togogenome.org/gene/10090:Ppp5c ^@ http://purl.uniprot.org/uniprot/Q60676 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by at least two different proteolytic cleavages producing a 56 kDa and a 50 kDa form.|||Animals are fertile with a growth rate equivalent to that of wild-type. Males weigh less, exhibit reduced fasting glycaemia and improved glucose tolerance, but retain normal insulin sensitivity.|||Autoinhibited. In the autoinhibited state, the TPR domain interacts with the catalytic region and prevents substrate access to the catalytic pocket. Allosterically activated by various polyunsaturated fatty acids, free long-chain fatty-acids and long-chain fatty acyl-CoA esters, arachidonic acid being the most effective activator. HSP90A and probably RAC1, GNA12 and GNA13 can also release the autoinhibition by the TPR repeat. Activation by RAC1, GNA12 and GNA13 is synergistic with the one produced by fatty acids binding. Inhibited by okadaic acid.|||Belongs to the PPP phosphatase family. PP-5 (PP-T) subfamily.|||Binds 2 Mg(2+) or Mn(2+) cations per subunit.|||Cell membrane|||Cytoplasm|||Does not show circadian oscillation.|||Expressed in liver (at protein level) and brain, enriched in suprachiasmatic nuclei.|||Nucleus|||Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2 (By similarity). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Part of a complex with HSP90/HSP90AA1 and steroid receptors (PubMed:9195923). Interacts (via TPR repeats) with HSP90AA1 (via TPR repeat-binding motif) or HSPA1A/HSPA1B; the interaction is direct and activates the phosphatase activity (By similarity). Dissociates from HSPA1A/HSPA1B and HSP90AA1 in response to arachidonic acid (By similarity). Interacts with CPNE1 (via VWFA domain) (PubMed:12522145). Interacts with CDC16, CDC27 (By similarity). Interacts with KLHDC10 (via the 6 Kelch repeats); inhibits the phosphatase activity on MAP3K5 (By similarity). Interacts with ATM and ATR; both interactions are induced by DNA damage and enhance ATM and ATR kinase activity (By similarity). Interacts with RAD17; reduced by DNA damage (By similarity). Interacts with nuclear receptors such as NR3C1/GCR and PPARG (activated by agonist); regulates their transactivation activities (PubMed:9195923, PubMed:21994940). Interacts (via TPR repeats) with S100 proteins S100A1, S100A2, S100A6, S100B and S100P; the interactions are calcium-dependent, strongly activate PPP5C phosphatase activity and compete with HSP90AA1 and MAP3K5 interactions (By similarity). Interacts with SMAD2 and SMAD3 but not with SMAD1; decreases SMAD3 phosphorylation and protein levels (By similarity). Interacts (via TPR repeats) with CRY1 and CRY2; the interaction with CRY2 down-regulates the phosphatase activity on CSNK1E (By similarity). Interacts (via TPR repeats) with the active form of RAC1, GNA12 or GNA13; these interactions activate the phosphatase activity and translocate PPP5C to the cell membrane (By similarity). Interacts with FLCN (By similarity).|||Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT (PubMed:17376776, PubMed:21994940, PubMed:22526606). Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses (By similarity). Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1 (PubMed:17376776). Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress (By similarity). Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function (PubMed:21994940). Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1 (PubMed:21994940). Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E. May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels. Dephosphorylates and may play a role in the regulation of TAU/MAPT (By similarity). Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2 (By similarity). Dephosphorylate FNIP1, disrupting interaction with HSP90AA1/Hsp90 (By similarity). http://togogenome.org/gene/10090:Samsn1 ^@ http://purl.uniprot.org/uniprot/P57725 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in spleen and lymph node (at protein level).|||Interacts with FASLG (By similarity). Interacts with phosphotyrosine containing proteins. Interacts (via SH3 domain) with CTTN. Interacts (phosphorylated at Ser-23) with YWHAB, YWHAE, YWHAG, YWHAH, YWHAZ and SFN. Interacts directly with SAP30 and HDAC1. Identified in a complex with SAP30 and HDAC1.|||Negative regulator of B-cell activation. Down-regulates cell proliferation (in vitro). Promotes RAC1-dependent membrane ruffle formation and reorganization of the actin cytoskeleton. Regulates cell spreading and cell polarization. Stimulates HDAC1 activity. Regulates LYN activity by modulating its tyrosine phosphorylation.|||No visible phenotype. Mice have normal bone marrow B-cell development and normal splenic T- and B-cell populations, but show an enhanced immune response upon immunization. Mice have constitutively activated Lyn, due to constitutive Lyn tyrosine phosphorylation.|||Nucleus|||Up-regulated in peripheral blood B-cells by IL4 and bacterial lipopolysaccharide (LPS).|||ruffle http://togogenome.org/gene/10090:Tmprss3 ^@ http://purl.uniprot.org/uniprot/Q3TZ06|||http://purl.uniprot.org/uniprot/Q8K1T0 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Endoplasmic reticulum membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Probable serine protease that plays a role in hearing. Acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival. Activates ENaC (in vitro).|||Strongly expressed in liver, cochlea, brain, cerebellum, spleen, lung, and muscle and at a lower degree in retina, kidney, and heart. Expressed in the spiral ganglion, the cells supporting the organ of Corti and the stria vascularis. Isoform 2 is strongly expressed only in the cochlea with very faint expression in the cerebellum, spleen and muscle.|||Undergoes autoproteolytic activation. http://togogenome.org/gene/10090:Coch ^@ http://purl.uniprot.org/uniprot/Q62507 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in inner ear structures.|||Monomer. May form homodimer. Interacts with type II collagen. Interacts with SLC44A2. Interacts with ANXA2.|||N-glycosylated.|||Plays a role in the control of cell shape and motility in the trabecular meshwork.|||extracellular space http://togogenome.org/gene/10090:Tkfc ^@ http://purl.uniprot.org/uniprot/Q8VC30 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the dihydroxyacetone kinase (DAK) family.|||Catalyzes both the phosphorylation of dihydroxyacetone and of glyceraldehyde, and the splitting of ribonucleoside diphosphate-X compounds among which FAD is the best substrate. Represses IFIH1-mediated cellular antiviral response.|||DhaK and DhaL domains have differential roles, individually DhaK is inactive and DhaL displays cyclase but not kinase activity.|||Each activity is inhibited by the substrate(s) of the other.|||Homodimer (By similarity). Interacts with IFIH1 (via the CARD domains), the interaction is inhibited by viral infection (By similarity).|||Manganese or cobalt are requested for FAD-AMP lyase activity. http://togogenome.org/gene/10090:Otud6a ^@ http://purl.uniprot.org/uniprot/Q6IE21 ^@ Function ^@ Deubiquitinating enzyme that hydrolyzes 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains (By similarity). http://togogenome.org/gene/10090:Slc10a4 ^@ http://purl.uniprot.org/uniprot/A2RTJ6|||http://purl.uniprot.org/uniprot/Q3UEZ8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated following N-terminal proteolytic cleavage by thrombin and/or proteases.|||Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Cell membrane|||Highest expression in the brain and significantly above background levels in the eye, prostate, and whole embryo tissue preparations.|||Membrane|||Transporter for bile acids. http://togogenome.org/gene/10090:Pls3 ^@ http://purl.uniprot.org/uniprot/Q99K51 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Actin-bundling protein.|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Ndufs3 ^@ http://purl.uniprot.org/uniprot/Q9DCT2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I 30 kDa subunit family.|||Conditional knockout (KO) in the forebrain neurons results in reduced complex I activity, altered brain energy metabolism, increased locomotor activity with impaired motor coordination, balance and stereotyped behavior, neuroinflammation in cortex and hippocampus, and neuronal death in hippocampus (PubMed:33148885). Conditional KO in skeletal muscle results in development of a progressive myopathy resulting in premature death, muscle degeneration accompanied by increased mitochondrial proliferation and serum lactic acidosis and a decrease in complex I activity, assembly and expression in muscle (PubMed:31916679).|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits (By similarity). Interacts with NDUFAF3 (By similarity). Interacts with RAB5IF (PubMed:31536960). Found in subcomplexes containing subunits NDUFS2, MT-ND1 and NDUFA13 (By similarity).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:31916679, PubMed:33148885). Essential for the catalytic activity and assembly of complex I (PubMed:31916679, PubMed:33148885).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Oosp2 ^@ http://purl.uniprot.org/uniprot/Q4FZG8 ^@ Caution|||Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PLAC1 family.|||Deficient mice are viable, with no overt abnormalities. Female mice are fertile. Triple-gene deletion of OOSP1-3 in mice retains fertility but causes significantly lower blastocyst and reduced offspring number.|||Expressed in ovaries. Highly expressed in the germinal vesicles oocytes and metaphase II oocytes.|||Secreted|||Unlike human OOSP2, mouse OOSP2 seems not participate in folliculogenesis and oocyte maturation. http://togogenome.org/gene/10090:Il9 ^@ http://purl.uniprot.org/uniprot/P15247 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-7/IL-9 family.|||Deltion mice do not show defects in T-cell development or differentiation, the generation of naive or antigen-driven antibody responses, or the expulsion of the intestinal parasitic nematode Nippostrongylus brasiliensis. However, mastocytosis is severely impaired in these animals.|||Interacts with IL9R (PubMed:2145361). Interacts with IL2RG (PubMed:7718508).|||Multifunctional cytokine secreted mainly by T-helper 2 lymphocytes and also mast cells or NKT cells that plays important roles in the immune response against parasites (PubMed:11070175, PubMed:19433802). Affects intestinal epithelial permeability and adaptive immunity (PubMed:12704113). In addition, induces the differentiation of specific T-cell subsets such as IL-17 producing helper T-cells (TH17) and also proliferation and differentiation of mast cells (PubMed:19433802, PubMed:11070175). Mechanistically, exerts its biological effects through a receptor composed of IL9R subunit and a signal transducing subunit IL2RG (PubMed:2145361, PubMed:7718508). Receptor stimulation results in the rapid activation of JAK1 and JAK3 kinase activities leading to STAT1, STAT3 and STAT5-mediated transcriptional programs (PubMed:10464327). Induction of differentiation genes seems to be mediated by STAT1 alone, while protection of cells from apoptosis depends on STAT3 and STAT5 (PubMed:10464327).|||Secreted http://togogenome.org/gene/10090:Ncapg2 ^@ http://purl.uniprot.org/uniprot/Q6DFV1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the condensin-2 complex, which contains the SMC2 and SMC4 heterodimer, and 3 non SMC subunits that probably regulate the complex: NCAPH2, NCAPD3 and NCAPG2.|||Expressed from 7 dpc when yolk sac hematopoiesis is initiated. Between 12.5 dpc and 15.5 dpc restricted to the developing fetal liver and the site of definitive hematopoiesis. Detected in thymus at 15.5 dpc as well as the midbrain, forebrain and the olfactory epithelium.|||Expressed in spleen, lung and testis as well as in hematopoietic cell lines.|||Nucleus|||Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis. Is required for early embryonic development and is essential for viability and expansion of the inner cell mass (ICM) of the implanting blastocyst. http://togogenome.org/gene/10090:Arpc3 ^@ http://purl.uniprot.org/uniprot/Q9JM76 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ARPC3 family.|||Cell projection|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC.|||Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Gli3 ^@ http://purl.uniprot.org/uniprot/B2RUG4|||http://purl.uniprot.org/uniprot/Q61602 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GLI C2H2-type zinc-finger protein family.|||Cytoplasm|||Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.|||Nucleus|||Phosphorylated by DYRK2 (in vitro) (By similarity). Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylation is essential for its proteolytic processing.|||Several mutations result in developmental defects of cranofacial and limb structures. In particular the add (anterior digit-pattern deformity) and pdn (polydactyly Nagoya) alleles.|||The phosphorylated form interacts with BTRC (By similarity). The full-length GLI3 form (GLI3FL) interacts with SUFU and this interaction regulates the formation of either repressor or activator forms of GLI3. Its association with SUFU is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A. Interacts with KIF7. The activator form of GLI3 (GLI3A) but not the repressor form (GLI3R) can interact with TRPS1. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains 3, 4 and 5); the interaction enhances its transcriptional activity (By similarity). Interacts with WRD11; the interaction associates EMX1 with GLI3 (PubMed:29263200). Interacts with DZIP1; retains GLI3 within the cytoplasm (PubMed:23955340).|||Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3.|||cilium http://togogenome.org/gene/10090:Slc9a5 ^@ http://purl.uniprot.org/uniprot/B2RXE2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Deficient mice are born at normal Mendelian ratios without gross abnormalities in postnatal development. However, deficient mice display significant enhancement of learning and memory accompanied by an increase in the number of hippocampal excitatory synapses in the hippocampus.|||Highest expression level is detected in brain (PubMed:28981195). Expressed in hippocampal neurons (at protein level) (PubMed:21551074).|||Interacts with CHP1 and CHP2 (By similarity). Interacts with ARRB2; facilitates the endocytosis of SLC9A5 from the plasma membrane (By similarity). Interacts with RACK1; this interaction positively regulates SLC9A5 activity and promote SLC9A5 localization to focal adhesions (By similarity). Interacts with SCAMP2; this interaction regulates SLC9A5 cell-surface targeting and SLC9A5 activity (By similarity).|||Phosphorylated by PRKAA2; promotes its accumulation at the cell surface. Phosphorylated by CSNK2A1 in a manner favoring its beta-arrestin binding and endocytosis.|||Plasma membrane Na(+)/H(+) antiporter. Mediates the electroneutral exchange of intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry. Responsible for regulating intracellular pH homeostasis, in particular in neural tissues. Acts as a negative regulator of dendritic spine growth. Plays a role in postsynaptic remodeling and signaling. Can also contribute to organellar pH regulation, with consequences for receptor tyrosine kinase trafficking.|||Recycling endosome membrane|||Synaptic cell membrane|||dendritic spine membrane|||focal adhesion http://togogenome.org/gene/10090:Oaz2 ^@ http://purl.uniprot.org/uniprot/O08608 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ODC antizyme family.|||Interacts with ODC1 and thereby sterically blocks ODC homodimerization (By similarity). Interacts with AZIN2; this interaction disrupts the interaction between the antizyme and ODC1 (PubMed:16916800).|||Nucleus|||Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity (PubMed:16916800, PubMed:18508777, PubMed:24967154). Involved in the translocation of AZIN2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol (PubMed:19449338). http://togogenome.org/gene/10090:Fpr-rs6 ^@ http://purl.uniprot.org/uniprot/Q3SXG2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Expressed exclusively in vomeronasal tissue (PubMed:19387439, PubMed:19497865). Expressed in 1.2 % of a subset of sensory neurons located in the apical layer of the vomeronasal organ. Each neuron appears to express only one receptor gene. Expressed in brain, spleen, skeletal muscle and at high level in testis (PubMed:12459252).|||May have an olfactory function associated with the identification of pathogens or of pathogenic states.|||Membrane http://togogenome.org/gene/10090:Egln3 ^@ http://purl.uniprot.org/uniprot/Q91UZ4 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||Detected at 8.5 dpc in proliferating myoblasts of the dermomyotome and the developing heart tube. From dermomyotomal cells of the rostral somites expression progressed in a rostral to caudal pattern, with highest levels seen in the muscle primordia and mature muscles.|||Highly expressed in cardiac and smooth muscle. Also high expression in brain, skeletal muscle and kidney. Low levels in lung.|||Induced by hypoxia. Up-regulated in proliferating myoblasts induced to form differentiated myotubes.|||Interacts with ADRB2; the interaction hydroxylates ADRB2 facilitating its ubiquitination by the VHL-E3 ligase complex (By similarity). Interacts with PKM; the interaction hydroxylates PKM in hypoxia (By similarity). Interacts with WDR83; the interaction leads to almost complete elimination of HIF-mediated reporter activity (By similarity). Interacts with BCL2 (via its BH4 domain); the interaction disrupts the BAX-BCL4 complex inhibiting the anti-apoptotic activity of BCL2 (By similarity). Interacts with LIMD1, WTIP and AJUBA (By similarity).|||Nucleus|||Null mice exhibit reduced apoptosis of in sympathetic neurons. However, the sympathoadrenal system appears hypofunctional with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. There is an increase in ADRB2 abundance and decrease of ADRB1 abundance in heart.|||Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as PKM, TELO2, ATF4 and HIF1A (PubMed:24809345). Target proteins are preferentially recognized via a LXXLAP motif (By similarity). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (By similarity). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (By similarity). Also hydroxylates HIF2A (By similarity). Has a preference for the CODD site for both HIF1A and HIF2A (By similarity). Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site (By similarity). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (By similarity). Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes (By similarity). ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia (By similarity). Also hydroxylates PKM in hypoxia, limiting glycolysis (By similarity). Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis (By similarity). In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex (By similarity). In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity (By similarity). Also essential for hypoxic regulation of neutrophilic inflammation (PubMed:21317538). Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway (By similarity). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (PubMed:24809345).|||The Beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.|||Ubiquitinated by SIAH1 and/or SIAH2 in response to the unfolded protein response (UPR), leading to its degradation. http://togogenome.org/gene/10090:Vps33b ^@ http://purl.uniprot.org/uniprot/P59016|||http://purl.uniprot.org/uniprot/Q8C076 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Early endosome|||Endosome membrane|||Increased platelet account and deficiency in platelet alpha-granules associated with bleeding diathesis and decreases aggregate formation; reduction of mature ype-II multivesicular bodies (MVB II) in megakaryocytes.|||Interacts with RAB11A and VIPAS39 (PubMed:20190753). Associates with adapter protein complex 3 (AP-3), clathrin:AP-3 and clathrin:HGS complexes (PubMed:21411634).|||Late endosome membrane|||Lysosome membrane|||May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. Required for proper trafficking and targeting of the collagen-modifying enzyme lysyl hydroxylase 3 (LH3) to intracellular collagen (By similarity). Mediates phagolysosomal fusion in macrophages. Proposed to be involved in endosomal maturation implicating in part VIPAS39 (By similarity). In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical RAB11A-dependentrecycling pathway and in the maintenance of the apical-basolateral polarity (PubMed:20190753). Seems to be involved in the sorting of specific cargos from the trans-Golgi network to alpha-granule-destined multivesicular bodies (MVBs) promoting MVBs maturation in megakaryocytes (PubMed:25947942).|||Phosphorylated on tyrosine residues.|||Recycling endosome|||Vps33b-deficient inner medullary collecting duct cells display abnormal expression of membrane proteins such as Ceacam5, structural and functional tight junction defects and reduced E-cadherin expression.|||clathrin-coated vesicle http://togogenome.org/gene/10090:Ints2 ^@ http://purl.uniprot.org/uniprot/A0A1S6GWJ5|||http://purl.uniprot.org/uniprot/Q80UK8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 2 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Nucleus membrane http://togogenome.org/gene/10090:Proser1 ^@ http://purl.uniprot.org/uniprot/Q5PRE5 ^@ Function|||PTM|||Subunit ^@ Glycosylated. Interaction with OGT leads to GlcNAcylation.|||Interacts with TET2 and OGT; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2. Interacts with KDM6A. Interacts with TET1.|||Mediates OGT interaction with and O-GlcNAcylation of TET2 to control TET2 stabilization at enhancers and CpG islands (CGIs). http://togogenome.org/gene/10090:Taf2 ^@ http://purl.uniprot.org/uniprot/B9EJX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TAF2 family.|||Nucleus http://togogenome.org/gene/10090:Or52a33 ^@ http://purl.uniprot.org/uniprot/Q8VGY7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gmeb1 ^@ http://purl.uniprot.org/uniprot/Q3UYV4|||http://purl.uniprot.org/uniprot/Q9JL60 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Homodimer, and heterodimer of GMEB1 and GMEB2. Interacts with TRIM63 (By similarity). Interacts with the glucocorticoid receptor (NR3C1) and NCOA2/TIF2. May interact with HSP27 and CREB-binding protein (CBP).|||Nucleus|||Trans-acting factor that binds to glucocorticoid modulatory elements (GME) present in the TAT (tyrosine aminotransferase) promoter and increases sensitivity to low concentrations of glucocorticoids. Binds also to the transferrin receptor promoter (By similarity).|||Ubiquitous. Low levels were detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. http://togogenome.org/gene/10090:Vmn1r218 ^@ http://purl.uniprot.org/uniprot/Q8R261 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Tbc1d1 ^@ http://purl.uniprot.org/uniprot/Q60949 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in highest levels in hematopoietic cells, testis and kidney.|||Insulin-stimulated phosphorylation by AKT family kinases stimulates SLC2A4/GLUT4 translocation.|||Interacts with APPL2 (via BAR domain); interaction is dependent of TBC1D1 phosphorylation at Ser-229; interaction diminishes the phosphorylation of TBC1D1 at Thr-590, resulting in inhibition of SLC2A4/GLUT4 translocation and glucose uptake.|||May act as a GTPase-activating protein for Rab family protein(s). May play a role in the cell cycle and differentiation of various tissues. Involved in the trafficking and translocation of GLUT4-containing vesicles and insulin-stimulated glucose uptake into cells.|||Nucleus http://togogenome.org/gene/10090:Pgam2 ^@ http://purl.uniprot.org/uniprot/O70250|||http://purl.uniprot.org/uniprot/Q5NCI4 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.|||Expressed in the testes (at protein level).|||Homodimer (By similarity). Interacts with ENO1 (PubMed:23446454).|||Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase), but with a reduced activity. http://togogenome.org/gene/10090:Sult1b1 ^@ http://purl.uniprot.org/uniprot/Q9QWG7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Cytoplasm|||Expression was detected at very low level in liver from 1 day-old and then gradually increased to the maximum level at 4 weeks old.|||Liver specific.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of dopamine, small phenols such as 1-naphthol and p-nitrophenol and thyroid hormones, including 3,3'-diiodothyronine, triidothyronine (T3) and reverse triiodothyronine (rT3) (PubMed:9644246). May play a role in gut microbiota-host metabolic interaction. O-sulfonates 4-ethylphenol (4-EP), a dietary tyrosine-derived metabolite produced by gut bacteria. The product 4-EPS crosses the blood-brain barrier and may negatively regulate oligodendrocyte maturation and myelination, affecting the functional connectivity of different brain regions associated with the limbic system (By similarity). http://togogenome.org/gene/10090:Lce1a2 ^@ http://purl.uniprot.org/uniprot/Q9D1K4 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Gm4513 ^@ http://purl.uniprot.org/uniprot/A0A140LJ87 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Chic2 ^@ http://purl.uniprot.org/uniprot/Q9D9G3 ^@ PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CHIC family.|||Golgi apparatus|||Membrane|||Palmitoylation in the CHIC motif is required for membrane association. http://togogenome.org/gene/10090:Rps15 ^@ http://purl.uniprot.org/uniprot/D3YTQ9|||http://purl.uniprot.org/uniprot/P62843 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS19 family.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the small ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Apold1 ^@ http://purl.uniprot.org/uniprot/E9Q0X2 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Lmbrd2 ^@ http://purl.uniprot.org/uniprot/Q8C561 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LIMR family.|||Cell membrane|||Recruited to ligand-activated beta-2 adrenergic receptor/ADRB2, it negatively regulates the adrenergic receptor signaling pathway. May also regulate other G-protein coupled receptors including type-1 angiotensin II receptor/AGTR1. http://togogenome.org/gene/10090:Igsf5 ^@ http://purl.uniprot.org/uniprot/Q7TSN7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the immunoglobulin superfamily.|||Interacts with MAGI1 at tight junctions, forms a tripartite complex with NPHS1 (By similarity). Interacts with LNX1 isoform 2 via its PDZ 2 domain, it may also interact with other isoforms containing this domain.|||Localized to kidney glomeruli and small intestinal epithelial cells. In kidney glomeruli, it is localized at slit diaphragm. Also found in spermatogonia, gonocytes, hematopoietic stem cells and Sertoli cells.|||N-glycosylated.|||No visible phenotype.|||Provides, together with MAGI1, an adhesion machinery at tight junctions, which may regulate the permeability of kidney glomerulus and small intestinal epithelial cells. Mediates calcium-independent homophilic cell adhesion. In testis, it may function as a cell adhesion molecule rather than a tight-junction protein. It may participate in the adhesion between spermatogonia-spermatogonia, spermatogonia-Sertoli cells, and Sertoli cells-Sertoli cells.|||tight junction http://togogenome.org/gene/10090:Abca8b ^@ http://purl.uniprot.org/uniprot/A2AM56|||http://purl.uniprot.org/uniprot/Q8K440 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the ABC transporter superfamily. ABCA family.|||Cell membrane|||Cholesterol efflux is increased by extracellularly applied taurocholate.|||Down-regulated by digoxin.|||Expressed during embryogenesis.|||Expressed in heart, brain, lung, liver and skeletal muscle (PubMed:12532264). Highly expressed in the liver, and is also abundant in heart and skeletal muscle (PubMed:28882873). Highly expressed in liver (PubMed:29300488).|||Mediates cholesterol and taurocholate efflux (PubMed:28882873). Through the interaction with ABCA1 potentiates the cholesterol efflux to lipid-free APOA1, in turn regulates high-density lipoprotein cholesterol levels (By similarity).|||Membrane http://togogenome.org/gene/10090:Il5ra ^@ http://purl.uniprot.org/uniprot/P21183|||http://purl.uniprot.org/uniprot/Q05A81 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell surface receptor that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:1873482). Acts by forming an heterodimeric receptor with CSF2RB subunit and subsequently binding to interleukin-5. In unstimulated conditions, interacts constitutively with JAK2. Heterodimeric receptor activation leads to JAK2 stimulation and subsequent activation of the JAK-STAT pathway.|||Expressed on eosinophils and basophils. Also on B-cells.|||Interacts with IL5 (PubMed:1873482). Interacts with CSF2RB. Interacts with JAK2. Interacts with SDCBP.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Pepd ^@ http://purl.uniprot.org/uniprot/A2RS23|||http://purl.uniprot.org/uniprot/Q11136 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the peptidase M24B family.|||Belongs to the peptidase M24B family. Eukaryotic-type prolidase subfamily.|||Binds 2 manganese ions per subunit.|||Dipeptidase that catalyzes the hydrolysis of dipeptides with a prolyl (Xaa-Pro) or hydroxyprolyl residue in the C-terminal position. The preferred dipeptide substrate is Gly-Pro, but other Xaa-Pro dipeptides, such as Ala-Pro, Met-Pro, Phe-Pro, Val-Pro and Leu-Pro, can be cleaved. Plays an important role in collagen metabolism because the high level of iminoacids in collagen.|||Homodimer. http://togogenome.org/gene/10090:Ech1 ^@ http://purl.uniprot.org/uniprot/O35459 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||Homohexamer.|||Isomerization of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA.|||Mitochondrion|||Peroxisome http://togogenome.org/gene/10090:Hapln1 ^@ http://purl.uniprot.org/uniprot/Q9QUP5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HAPLN family.|||Stabilizes the aggregates of proteoglycan monomers with hyaluronic acid in the extracellular cartilage matrix.|||Ubiquitously expressed.|||extracellular matrix http://togogenome.org/gene/10090:Foxd1 ^@ http://purl.uniprot.org/uniprot/Q61345 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ At 9.5 dpc embryos, expressed in a limited region of the neuroepithelium and also in the temporal half of the primary optic cup and the optic stalk. At 10.5 dpc, seen in the hypothalamus, temporal half of the optic stalk, and temporal hemiretina. At 12.5 dpc and 13.5 dpc a high expression is seen in regions of condensed mesenchyme of the head, and as neuroepithelial cells begin to differentiate and migrate outward from the ventricular zone, expression declines markedly. By 16.5 dpc levels are diminished and restricted to unfused pockets along the exhausted ventricular zone.|||Mice show disrupted cell identity in the ventrotemporal area of the retina and aberrant morphogenesis of the optic chiasm. Their kidneys remain fused, have a disorganised ureteric tree and fail to ascend to a lumbar position.|||Nucleus|||Predominantly expressed in the CNS and temporal half of the retina. Also expressed in the condensed head mesenchyme, metanephric blastema of the developing kidney, cortex of the adrenal gland, condensed mesenchyme at the base of the follicles of vibrassae and cartilage perichondrium of the developing vertebrate.|||Transcription factor involved in regulation of gene expression in a variety of processes including formation of positional identity in the developing retina, regionalization of the optic chiasm, morphogenesis of the kidney, and neuralization of ectodermal cells (PubMed:15509772, PubMed:15634693, PubMed:9811586). Involved in transcriptional activation of PGF and C3 genes (By similarity).|||Was originally assigned to be BF-2 (FOXG1). http://togogenome.org/gene/10090:Rfc3 ^@ http://purl.uniprot.org/uniprot/Q8R323 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the activator 1 small subunits family.|||Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA (By similarity). Interacts with CNTD1; this interaction facilitates crossover formation (PubMed:32640224).|||Nucleus|||The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. http://togogenome.org/gene/10090:Tepp ^@ http://purl.uniprot.org/uniprot/Q6IMH0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Deficient mice are viable and have normal fertility.|||Expressed in testis.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme. May serve to reinforce and thus stabilize the microtubule structure in the sperm flagella.|||flagellum axoneme http://togogenome.org/gene/10090:Mn1 ^@ http://purl.uniprot.org/uniprot/D3YWE6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By calcitrol (1,25-dihydroxyvitamin D3).|||Detected in brain, heart, tibia, and calvarial osteoclasts.|||Detected in the midbrain, hindbrain and craniofacial mesenchyme at 9.5 dpc. At 10.5 dpc and 11.5 dpc, strong expression is detected in the brain, frontonasal processes, maxillary processes, mandibular processes, the second brachial arch, and also in somites and limb buds. In the developing palatal shelves from 12.5 dpc-14.5 dpc, shows graded expression with highest levels in the posterior and middle regions and very low levels in the anterior region.|||Interacts with PBX1, PKNOX1, ZBTB24, E2F7, RING1.|||Lethality occurs at or shortly after birth, associated with cleft secondary palate (PubMed:15870292). Skulls at late embryonic stages show multiple abnormalities including complete loss of alisphenoid, squamosal and vomer bones, and poorly developed presphenoid and basisphenoid bones (PubMed:15870292). Other parts of the skeleton are not affected (PubMed:15870292). Early palate development is normal but later the palatal shelves fail to grow and elevate towards the midline, associated with both impaired cell division and apoptosis (PubMed:18948418).|||Nucleus|||Transcriptional activator which specifically regulates expression of TBX22 in the posterior region of the developing palate (PubMed:18948418). Required during later stages of palate development for normal growth and medial fusion of the palatal shelves (PubMed:18948418). Promotes maturation and normal function of calvarial osteoblasts, including expression of the osteoclastogenic cytokine TNFSF11/RANKL (PubMed:19386590). Necessary for normal development of the membranous bones of the skull (PubMed:15870292). May play a role in tumor suppression (By similarity). http://togogenome.org/gene/10090:Cyb561d2 ^@ http://purl.uniprot.org/uniprot/Q9WUE3 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 2 heme b groups non-covalently.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Highly expressed in the brain, lung, liver, and kidney (PubMed:17938141). Moderately expressed in the heart, placenta, skeletal muscle, and pancreas (PubMed:17938141).|||Transmembrane reductase that may use ascorbate as an electron donor in the cytoplasm and transfer electrons across endoplasmic reticulum membranes to reduce monodehydro-L-ascorbate radical and iron cations Fe(3+) in the lumen of that compartment. http://togogenome.org/gene/10090:Or2w3 ^@ http://purl.uniprot.org/uniprot/Q5NCC8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gucy1a1 ^@ http://purl.uniprot.org/uniprot/Q9ERL9 ^@ Activity Regulation|||Cofactor|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by nitric oxide in the presence of magnesium or manganese ions.|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Cytoplasm|||Has also activity with Mn(2+) (in vitro).|||The active enzyme is formed by a heterodimer of an alpha and a beta subunit. Heterodimer with GUCY1B1.|||There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. http://togogenome.org/gene/10090:Ephx1 ^@ http://purl.uniprot.org/uniprot/E9PWK1|||http://purl.uniprot.org/uniprot/Q9D379 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S33 family.|||Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.|||Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water. May play a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids. Metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and glycerol (By similarity).|||Endoplasmic reticulum membrane|||Inhibited by 10-hydroxystearamide and methoxy-arachidonyl fluorophosphate.|||Microsome membrane http://togogenome.org/gene/10090:Wars2 ^@ http://purl.uniprot.org/uniprot/Q9CYK1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Mitochondrial aminoacyl-tRNA synthetase that activate and transfer the amino acids to their corresponding tRNAs during the translation of mitochondrial genes and protein synthesis.|||Mitochondrion matrix http://togogenome.org/gene/10090:Dmxl2 ^@ http://purl.uniprot.org/uniprot/Q8BPN8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Conditional heterozygous deletion of the gene in neurons causes delayed puberty as well as very low fertility; the reproductive phenotype is associated with a reduced number of GnRH neurons in the hypothalamus of adult mice. Animals with a homozygous deletion of the gene die during embryonic development.|||Expressed in the brain and pituitary gland. Detected in the hippocampus, dentate gyrus, hypothalamus, pyriform cortex and the granular and molecular layers of the cerebellum of adult animals. In the hypothalamus, expression is observed in the arcuate nucleus, the ME, the organum vasculosum of the lamina terminalis, and the subfornical organ, the subcommissural organ, and the suprachiasmatic nucleus. Both tanycytes and hypothalamic neurosecretory neurons express the protein (PubMed:25248098). Expressed in the inner and outer hair cells as well as in the spiral ganglion neurons (PubMed:27657680). Expressed in insulin-secreting cells of the islets of Langerhans in the pancreas (PubMed:25248098).|||Interacts with MADD and RAB3GAP.|||May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles of neuronal and endocrine homeostatic processes (By similarity). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (PubMed:25248098).|||neuronal dense core vesicle|||synaptic vesicle membrane http://togogenome.org/gene/10090:Eif2ak2 ^@ http://purl.uniprot.org/uniprot/Q03963 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on several Ser, Thr and Tyr residues. Autophosphorylation of Thr-414 is dependent on Thr-409 and is stimulated by dsRNA binding and dimerization. Autophosphorylation apparently leads to the activation of the kinase. Tyrosine autophosphorylation is essential for efficient dsRNA-binding, dimerization, and kinase activation (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.|||By type I interferons.|||Cytoplasm|||Expressed in heart, lung, brain, kidney, testes, thymus and bone marrow.|||Homodimer. Interacts with DNAJC3 and STRBP (By similarity). Forms a complex with FANCA, FANCC, FANCG and HSP70 (By similarity). Interacts with ADAR/ADAR1. The inactive form interacts with NCK1. Interacts (via the kinase catalytic domain) with STAT3 (via SH2 domain), TRAF2 (C-terminus), TRAF5 (C-terminus) and TRAF6 (C-terminus). Interacts with MAP2K6, TARBP2, NLRP1, NLRC4 and AIM2. Interacts (via DRBM 1 domain) with DUS2L (via DRBM domain) (By similarity). Interacts with DHX9 (via N-terminus) and this interaction is dependent upon activation of the kinase. The inactive form interacts with GSN. Interacts with IKBKB/IKKB, NPM1, NLRP3 and IRS1.|||IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:20038207, PubMed:20478537, PubMed:21123651). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:21123651, PubMed:20631127). Exerts its antiviral activity on a wide range of DNA and RNA viruses including west nile virus (WNV), sindbis virus (SV), foot-and-mouth virus (FMDV), semliki Forest virus (SFV) and lymphocytic choriomeningitis virus (LCMV) (PubMed:19264662, PubMed:20585572, PubMed:20631127, PubMed:21994357). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, and IRS1 (PubMed:19229320, PubMed:23403623). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (By similarity). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948222, PubMed:23392680). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (By similarity). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (By similarity). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (By similarity). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494, PubMed:23401008). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (PubMed:22633459).|||Initially produced in an inactive form and is activated by binding to viral dsRNA, which causes dimerization and autophosphorylation in the activation loop and stimulation of function. ISGylation can activate it in the absence of viral infection. Can also be activated by heparin, pro-inflammatory stimuli, growth factors, cytokines, oxidative stress and the cellular protein PRKRA. Activity is markedly stimulated by manganese ions. Activation is blocked by the cellular proteins TARBP2, DUS2L, NPM1, NCK1 and ADAR (By similarity).|||Mice have significantly elevated numbers of bone marrow derived hematopoietic stem/progenitor cells (HSPCs) and which are more actively proliferating and resistant to stress.|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Gpr146 ^@ http://purl.uniprot.org/uniprot/Q99LE2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Myo3a ^@ http://purl.uniprot.org/uniprot/F6QNG5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||In the C-terminal section; belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||cytoskeleton http://togogenome.org/gene/10090:Caskin2 ^@ http://purl.uniprot.org/uniprot/Q8VHK1 ^@ Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||May not bind CASK. http://togogenome.org/gene/10090:Nxpe4 ^@ http://purl.uniprot.org/uniprot/Q52KP5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NXPE family.|||Secreted http://togogenome.org/gene/10090:Bcl2a1b ^@ http://purl.uniprot.org/uniprot/Q497M6 ^@ Similarity ^@ Belongs to the Bcl-2 family. http://togogenome.org/gene/10090:Mrps12 ^@ http://purl.uniprot.org/uniprot/O35680 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS12 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Wnt2b ^@ http://purl.uniprot.org/uniprot/O70283 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Wnt family.|||Detected at the dorsal midline at the level of the diencephalon and mesencephalon at 9.5 dpc. Detected at the level of the optic and otic vesicles at 9.5 dpc (PubMed:9545553). Detected in the lateral plate mesoderm surrounding the ventral aspect of the anterior foregut at 9.5 dpc (PubMed:19686689). Detected in the mesothelium encasing the lung, and at lower levels in the distal mesenchyme from 12.5 dpc to 14.5 dpc (PubMed:19686689).|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Interacts with FZD4 and FZD5 (By similarity).|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:19686689). Plays a redundant role in embryonic lung development (PubMed:19686689).|||No visible phenotype at birth (PubMed:19686689). Combined disruption of Wnt2 and Wnt2b leads to lung agenesis (PubMed:19686689).|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Tmem45a2 ^@ http://purl.uniprot.org/uniprot/B7ZWJ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Membrane http://togogenome.org/gene/10090:Prss2 ^@ http://purl.uniprot.org/uniprot/P07146 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Binds 1 Ca(2+) ion per subunit.|||Expressed in the pancreas, lung and kidney.|||extracellular space http://togogenome.org/gene/10090:Snrnp40 ^@ http://purl.uniprot.org/uniprot/Q6PE01 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex. Part of the U5 snRNP complex. Interacts with PRPF8. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Component of the minor spliceosome, which splices U12-type introns (By similarity).|||Nucleus|||Required for pre-mRNA splicing as component of the activated spliceosome. Component of the U5 small nuclear ribonucleoprotein (snRNP) complex and the U4/U6-U5 tri-snRNP complex, building blocks of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). http://togogenome.org/gene/10090:Tulp4 ^@ http://purl.uniprot.org/uniprot/Q3UH13|||http://purl.uniprot.org/uniprot/Q9JIL5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TUB family.|||Cytoplasm|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Nup88 ^@ http://purl.uniprot.org/uniprot/Q5QNU0|||http://purl.uniprot.org/uniprot/Q8BQF0|||http://purl.uniprot.org/uniprot/Q8CEC0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of nuclear pore complex.|||Interacts with NUP214/CAN. Interacts with NUP62 and NUP98.|||nuclear pore complex http://togogenome.org/gene/10090:Uqcc5 ^@ http://purl.uniprot.org/uniprot/Q8C1Q6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial ribosome. Interacts with UQCC6. Interacts with MT-CYB; interacts with newly synthesizes MT-CYB (By similarity). Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508).|||Belongs to the UQCC5 family.|||Mitochondrion inner membrane|||Required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III (CIII) or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative phosphorylation (PubMed:35977508). Mediates early complex III biogenesis (PubMed:35977508). Participates in regulating the levels of electron transport chain proteins, and therefore energy supply, in response to changes in energy demand (PubMed:35977508). Also required for cytochrome c oxidase complex (complex IV) assembly (By similarity). http://togogenome.org/gene/10090:Zbtb33 ^@ http://purl.uniprot.org/uniprot/Q8BN78 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain, heart, kidney, liver, lung, neuromuscular junctions, skeletal muscle, spleen and testis.|||Interacts with NCOR1 (By similarity). Self-associates. Interacts with CTNND1, and this interaction inhibits binding to both methylated and non-methylated DNA. Interacts with CTNND2. Interacts with KPNA2/RCH1, which may mediate nuclear import of this protein. Interacts with CBFA2T3 (By similarity).|||Nucleus|||Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' and also binds to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). May recruit the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. Contributes to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1 (By similarity). http://togogenome.org/gene/10090:Zbtb3 ^@ http://purl.uniprot.org/uniprot/Q91X45 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Asz1 ^@ http://purl.uniprot.org/uniprot/Q8VD46 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed exclusively in testis and ovary with higher levels in testis.|||Expressed in pachytene spermatocytes and early spermatids in the developing and adult testes and in oocytes in all stages of oogenesis in the ovary. Also expressed in preimplantive embryos.|||Interacts with DDX4, PIWIL1, RANBP9 and TDRD1.|||Mice are viable but show profound defect in male meiosis leading to male sterility. Testes display increased hypomethylation of retrotransposons and their subsequent expression as well as piRNAs suppression.|||Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with pi-bodies suggests a participation in the primary piRNAs metabolic process. Required prior to the pachytene stage to facilitate the production of multiple types of piRNAs, including those associated with repeats involved in regulation of retrotransposons. May act by mediating protein-protein interactions during germ cell maturation. http://togogenome.org/gene/10090:Rnf149 ^@ http://purl.uniprot.org/uniprot/Q3U2C5 ^@ Domain|||Function|||Subcellular Location Annotation ^@ E3 ubiquitin-protein ligase. Ubiquitinates BRAF, inducing its proteasomal degradation.|||Membrane|||The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme. http://togogenome.org/gene/10090:Otud7a ^@ http://purl.uniprot.org/uniprot/Q8R554 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C64 family.|||Cytoplasm|||Has deubiquitinating activity towards 'Lys-11'-linked polyubiquitin chains.|||Nucleus http://togogenome.org/gene/10090:Raver1 ^@ http://purl.uniprot.org/uniprot/Q9CW46 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cooperates with PTBP1 to modulate regulated alternative splicing events. Promotes exon skipping. Cooperates with PTBP1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA.|||Cytoplasm|||Interacts with PTBP1, RAVER2, VCL and ACTN1. Part of a complex containing RAVER1, VCL and ACTN1.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Rbsn ^@ http://purl.uniprot.org/uniprot/Q80Y56 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Early endosome membrane|||Interacts with EHD1, RAB4A, RAB5A, RAB22A, RAB24 and VPS45. Binds simultaneously to RAB4A and RAB5A in vitro. Interacts with RAB4A and RAB5A that has been activated by GTP binding (By similarity).|||Rab4/Rab5 effector protein acting in early endocytic membrane fusion and membrane trafficking of recycling endosomes. Required for endosome fusion either homotypically or with clathrin coated vesicles. Plays a role in the lysosomal trafficking of CTSD/cathepsin D from the Golgi to lysosomes. Also promotes the recycling of transferrin directly from early endosomes to the plasma membrane. Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate (PtdInsP3). Plays a role in the recycling of transferrin receptor to the plasma membrane (By similarity). http://togogenome.org/gene/10090:Dlx4 ^@ http://purl.uniprot.org/uniprot/P70436 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the distal-less homeobox family.|||Branchial arches, molar and incisor teeth and limbs.|||Expressed in the mesenchyme of the anterior palate at 12.5 dpc, prior to the time of palate closure. Expression levels decrease at later time periods after palate closure.|||May play a role in determining the production of hemoglobin S. May act as a repressor. During embryonic development, plays a role in palatogenesis.|||Nucleus http://togogenome.org/gene/10090:Lmna ^@ http://purl.uniprot.org/uniprot/P48678 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in liver and in bone marrow (at protein level) (PubMed:10579712, PubMed:21547077). Expressed in cardiomyocytes (PubMed:26436652).|||Farnesylation of prelamin-A/C facilitates nuclear envelope targeting.|||Homodimer of lamin A and lamin C (By similarity). Interacts with lamin-associated polypeptides IA, IB and TMPO-alpha, RB1 and with emerin (By similarity). Proteolytically processed isoform A interacts with NARF (By similarity). Interacts with SREBF1, SREBF2, SUN1, SUN2 and TMEM43 (PubMed:11929849, PubMed:16380439, PubMed:16648470, PubMed:18230648, PubMed:19843581, PubMed:19933576). Interacts with TMEM201 (PubMed:22349700). Prelamin-A/C interacts with EMD. Interacts with DMPK; may regulate nuclear envelope stability (By similarity). Interacts with MLIP (PubMed:26436652, PubMed:21498514). Interacts with SUV39H1; the interaction increases stability of SUV39H1 (PubMed:23695662). Interacts with ITSN1 isoform 2 (By similarity). Interacts with IFFO1; the interaction forms an interior nucleoskeleton and the recruitment to DNA double-strand breaks (By similarity).|||Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations. Phosphorylation status of S-22 determines its localization between double-strand break (DSB) sites and the nuclear matrix (By similarity).|||Interacts (via C-terminus) with LEMD2 (via N-terminus) (in vitro).|||Isoform C is phosphorylated on Ser-392, Ser-407 and Ser-409 at interphase.|||Isoform C2 may have a role in determining the organization of nuclear and chromosomal structures during spermatogenesis.|||Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin (PubMed:10579712). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10579712). Recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (By similarity). Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10579712). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:11799477, PubMed:19124654, PubMed:21547077, PubMed:23535822). Required for osteoblastogenesis and bone formation (By similarity). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone. Required for cardiac homeostasis (PubMed:21982926, PubMed:26436652).|||Mutant mice survive postnatally for 6-8 weeks and show skeletal and cardiac myopathy, sarcopenia, osteopenia, decreased bone formation, neuropathy, abnormal neuromuscular junctions, decreased skeletal muscle growth and decreased muscle satellite cell proliferation. They develop ventricular dilation and cardiac dysfunction. Within 2-3 weeks they show a reduction in their growth rate and by week 4 their growth ceases with their mean body weight being half of that of the wild-type or the heterozygous littermates. Simultaneous knockout of LMNA and LAP2 results in partial rescue of the phenotype, with a 30% increase in survival rate and a 25-50% increase in body weight. Double knockouts for MLIP and LMNA die sooner than single LMNA knockout. They develop much more severe ventricular dilation and cardiac dysfunction (PubMed:26436652).|||Nucleus|||Nucleus envelope|||Nucleus lamina|||Nucleus matrix|||Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.|||Proteolytic cleavage of the C-terminal of 18 residues of prelamin-A/C results in the production of lamin-A/C (PubMed:17652517). The prelamin-A/C maturation pathway includes farnesylation of CAAX motif by protein farnesyltransferase (FNTA and FNTB), removal of the last three amino acids (-AAX) by RCE1/FACE2 and/or ZMPSTE24, methylation of the C-terminal cysteine by ICMT and endoproteolytic removal of the last 15 C-terminal amino acids by ZMPSTE24 (PubMed:17652517). Proteolytic cleavage requires prior farnesylation and methylation, and absence of these blocks cleavage (PubMed:17652517).|||Specifically expressed in germ cells.|||Sumoylation is necessary for the localization to the nuclear envelope.|||The N-terminus is blocked.|||The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.|||nucleoplasm http://togogenome.org/gene/10090:Xpo7 ^@ http://purl.uniprot.org/uniprot/Q9EPK7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the exportin family.|||Binds to nucleoporins. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. Interacts with ARHGAP1 and SFN. Interacts with Ran and cargo proteins in a GTP-dependent manner (By similarity).|||Cytoplasm|||Highly expressed in testis and spleen, moderate in kidney and liver and low in heart, brain, lung and skeletal muscle.|||Mediates the nuclear export of proteins (cargos) with broad substrate specificity. In the nucleus binds cooperatively to its cargo and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. XPO7 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or4b1d ^@ http://purl.uniprot.org/uniprot/Q7TQZ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:5730409E04Rik ^@ http://purl.uniprot.org/uniprot/Q8BP99 ^@ Similarity ^@ Belongs to the UPF0500 family. http://togogenome.org/gene/10090:Obsl1 ^@ http://purl.uniprot.org/uniprot/D3YYU8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Interacts with CCDC8. Interacts with CUL7; the interaction is direct. Interacts with FBXW8. Interacts (via N-terminal Ig-like domain) with TTN/titin (via C-terminal Ig-like domain); the interaction is direct (By similarity).|||Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer. Acts as a regulator of the Cul7-RING(FBXW8) ubiquitin-protein ligase, playing a critical role in the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Required to localize CUL7 to the Golgi apparatus in neurons (By similarity).|||Cytoplasm|||Golgi apparatus|||perinuclear region http://togogenome.org/gene/10090:Edar ^@ http://purl.uniprot.org/uniprot/Q9R187 ^@ Developmental Stage|||Disease Annotation|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Binds to EDARADD. Associates with TRAF1, TRAF2, TRAF3 and NIK.|||By activin A in 12 dpc dental epithelium.|||Defects in Edar are a cause of the downless phenotype in mice (the equivalent of anhidrotic ectodermal dysplasia in humans). The disease is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.|||Membrane|||Receptor for EDA isoform TAA, but not for EDA isoform TA-2 (By similarity). May mediate the activation of NF-kappa-B and JNK. May promote caspase-independent cell death.|||Transcripts are not detectable in the branchial arch epithelium before morphological tooth formation (10 dpc), but are highly expressed during the initiation of tooth development (11 dpc). Starting 12 dpc, expression is high and limited to the budding cells, and remains high in the fully developed enamel knot at 14 dpc, whereas all other dental cells were completely negative. During 15 dpc the enamel knot disappears largely through apoptosis, and no transcripts were detected in the tooth germs of newborns. In skin, uniformly distributed in the basal cells of the epidermis before follicle initiation. Expression becomes focally elevated before placodes become distinguishable. By 17 dpc transcripts are almost exclusively confined to maturing follicles and the recently initiated placodes. http://togogenome.org/gene/10090:Mrpl53 ^@ http://purl.uniprot.org/uniprot/Q9D1H8 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL53 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Mettl24 ^@ http://purl.uniprot.org/uniprot/Q8CCB5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methyltransferase superfamily.|||Probable methyltransferase.|||Secreted http://togogenome.org/gene/10090:Maneal ^@ http://purl.uniprot.org/uniprot/Q6P1J0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 99 family.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Neu3 ^@ http://purl.uniprot.org/uniprot/Q543I9|||http://purl.uniprot.org/uniprot/Q9JMH7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 33 family.|||Cell membrane|||Early endosome membrane|||Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides. Displays high catalytic efficiency for gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3 (PubMed:17708748, PubMed:10713120, PubMed:11696012, PubMed:14970224). Plays a role in the regulation of transmembrane signaling through the modulation of ganglioside content of the lipid bilayer and by direct interaction with signaling receptors, such as EGFR. Desialylates EGFR and activates downstream signaling in proliferating cells. Contributes to clathrin-mediated endocytosis by regulating sorting of endocytosed receptors to early and recycling endosomes (By similarity).|||Expressed in heart, brain and cerebral cortex.|||Interacts with CAV1; this interaction enhances NEU3 sialidase activity within caveola. Interacts with EGFR; this interaction mediates desialylation of EGFR and enhances downstream signaling.|||Lysosome membrane|||Palmitoylated; may regulate intracellular trafficking and anchorage to plasma membrane and endomembranes.|||Recycling endosome membrane|||caveola http://togogenome.org/gene/10090:Ect2 ^@ http://purl.uniprot.org/uniprot/Q07139 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoinhibited by the C-terminal PH domain which folds back and binds to the surface of the DH domain, blocking binding of RHOA to the catalytic center of the DH domain. The 2nd BRCT domain is also involved in inhibition, probably by helping to impede RHOA binding. Allosterically activated by binding of activated GTP-bound RHOA to the PH domain which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the catalytic center. Binding of phosphorylated RACGAP1 to the N-terminal BRCT domain-containing region also releases autoinhibition.|||Cell junction|||Cleavage furrow|||Cytoplasm|||Erroneous CDS prediction.|||Expressed in the embryo at 16 dpc.|||Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death.|||Highest expression in testis. Also detectable in brain, kidney, liver and spleen.|||Homodimer (By similarity). Homooligomer (By similarity). Found in the centralspindlin complex (By similarity). Interacts with NR1I3 (PubMed:17904126). Interacts (Thr-359 phosphorylated form) with PARD6A; the interaction is observed in cancer cells (By similarity). Interacts (Thr-359 phosphorylated form) with PRKCI; the interaction is observed in cancer cells (By similarity). Interacts with PKP4; the interaction is observed at the midbody (By similarity). Interacts with RACGAP1; the interaction is direct, occurs in a microtubule-dependent manner, occurs at anaphase and during cytokinesis, is inhibited in metaphase by phosphorylation of ECT2 on Thr-373 and is stimulated in early anaphase by dephosphorylation of ECT2 probably on Thr-373 through CDK1 activity (By similarity). Interacts with PLK1; the interaction is stimulated upon its phosphorylation on Thr-444 (By similarity). Interacts with RHOA; the interaction results in allosteric activation of ECT2 (By similarity). Interacts with KIF23, PARD3, PARD6B and PRKCQ (By similarity). Interacts with NEDD9/HEF1 (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Midbody|||Nucleus|||Phosphorylated by PLK1 in vitro. Hyperphosphorylated during the G2 phase of the cell cycle. Phosphorylation at Thr-373 occurs during the G2/M phase, relieves its auto-inhibition status and stimulates its GEF activity. Phosphorylation at Thr-444 in G2/M phase is required for subsequent binding with PLK1 and Rho exchange activation. Dephosphorylated at the time of cytokinesis. Phosphorylation at Thr-359 is required for its transformation activity in cancer cells (By similarity).|||The BRCT domain 1 and 2 are required for the intramolecular interaction, but not for the intermolecular oligomerization. The BRCT domains negatively inhibit its GEF activity in interphase cells. The same BRCT domains may act as a positive regulatory motif for the completion of cytokinesis after the breakdown of nuclear membrane during mitosis (By similarity).|||Up-regulated by phenobarbital in the nucleus and cytoplasm of the liver.|||spindle|||tight junction http://togogenome.org/gene/10090:Cd180 ^@ http://purl.uniprot.org/uniprot/Q62192 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ B-lymphocytes and spleen. Not detected in thymus, kidney, muscle, heart, brain or liver.|||Belongs to the Toll-like receptor family.|||Cell membrane|||M-shaped tetramer of two CD180-LY86 heterodimers.|||May cooperate with MD-1 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) in B-cells. Leads to NF-kappa-B activation. Also involved in the life/death decision of B-cells. http://togogenome.org/gene/10090:Or2a25 ^@ http://purl.uniprot.org/uniprot/Q8VGP6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cux1 ^@ http://purl.uniprot.org/uniprot/E9QKE9|||http://purl.uniprot.org/uniprot/H3BJN3|||http://purl.uniprot.org/uniprot/H3BK24|||http://purl.uniprot.org/uniprot/H3BKT0|||http://purl.uniprot.org/uniprot/H3BLS0|||http://purl.uniprot.org/uniprot/P53564|||http://purl.uniprot.org/uniprot/Q5BL05|||http://purl.uniprot.org/uniprot/Q6AXG1|||http://purl.uniprot.org/uniprot/Q9JJB6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa by CTSL. Cell cycle-dependent processing of CUX1 serves to generate a CDP/Cux p110 with distinct DNA binding and transcriptional properties.|||Asn-1285 may participate in regulating DNA-binding activity by promoting homo- and heterodimerization.|||Belongs to the CASP family.|||Belongs to the CUT homeobox family.|||Brains from knockout mice show neurons in layer II-III with a significant decrease in the dendritic length and the number of branches, as well as a severe reduction of dendritic spines density.|||Golgi apparatus membrane|||In postpubertal testis, isoform 6 is expressed from stages IV-V of spermatogenesis in the outer layer of round spermatids. Expression continues through stages VI-VII but no expression is detected in stages IX-XI. In prepubertal testis, isoform 6 is expressed in post-meiotic germ cells at the round spermatid stage.|||Interacts with BANP. Interacts with SATB1 (via DNA-binding domains); the interaction inhibits the attachment of both proteins to DNA.|||Membrane|||Nucleus|||Phosphorylated by PKA.|||Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1.|||Testis-specific where it is expressed in germ cells.|||Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III (PubMed:20510857). Also involved in the control of synaptogenesis (Probable). In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. http://togogenome.org/gene/10090:Hhatl ^@ http://purl.uniprot.org/uniprot/Q9D1G3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the membrane-bound acyltransferase family. HHAT subfamily.|||Endoplasmic reticulum membrane|||Interacts with SHH.|||Negatively regulates N-terminal palmitoylation of SHH by HHAT/SKN. http://togogenome.org/gene/10090:Runx1 ^@ http://purl.uniprot.org/uniprot/G3UWD2|||http://purl.uniprot.org/uniprot/G3X9W7|||http://purl.uniprot.org/uniprot/Q3UM65|||http://purl.uniprot.org/uniprot/Q8BQ09 ^@ Function|||Subcellular Location Annotation ^@ Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX.|||Nucleus http://togogenome.org/gene/10090:Atpif1 ^@ http://purl.uniprot.org/uniprot/O35143 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase inhibitor family.|||Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase (By similarity). Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing FECH to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme (PubMed:23135403).|||Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 74-106, leaving each N-terminal inhibitory region (residues 26-52) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 26-52) binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity (By similarity).|||Homodimer; represents the active form and is present at a pH value below 6.5. Homotetramer; represents the inactive form and is present at a pH value above 7.0 (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Mfsd11 ^@ http://purl.uniprot.org/uniprot/Q8BJ51 ^@ Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the unc-93 family.|||Despite its name it is related to the unc-93 family and not to the major facilitator superfamily.|||Membrane|||Widely expressed. http://togogenome.org/gene/10090:Tmem184b ^@ http://purl.uniprot.org/uniprot/A0A2I3BQI5|||http://purl.uniprot.org/uniprot/Q8BG09 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM184 family.|||May activate the MAP kinase signaling pathway.|||Membrane http://togogenome.org/gene/10090:Csnk2b ^@ http://purl.uniprot.org/uniprot/G3UZX4|||http://purl.uniprot.org/uniprot/P67871 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the casein kinase 2 subunit beta family.|||Casein kinase II/CK2 is a tetramer composed of an alpha subunit, an alpha' subunit and two beta subunits. The beta subunit dimerization is mediated by zinc ions. Interacts with DYNLT2 (By similarity). Interacts with CD163. Also a component of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, the complex associating following UV irradiation. Interacts with MUSK; mediates phosphorylation of MUSK by CK2. Interacts with FGF1; this interaction is increased in the presence of FIBP, suggesting a possible cooperative interaction between CSNKB and FIBP in binding to FGF1 (By similarity). Interacts (via KSSR motif) with ARK2N. Interacts with JUN and ARK2N; mediates the interaction between ARK2N and JUN (By similarity).|||Nucleus|||Phosphorylated by alpha subunit.|||Regulatory subunit of casein kinase II/CK2. As part of the kinase complex regulates the basal catalytic activity of the alpha subunit a constitutively active serine/threonine-protein kinase that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:16818610). Participates in Wnt signaling (PubMed:10806215).|||Regulatory subunit of casein kinase II/CK2. As part of the kinase complex regulates the basal catalytic activity of the alpha subunit a constitutively active serine/threonine-protein kinase that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Participates in Wnt signaling.|||Tetramer of two alpha and two beta subunits.|||The KSSR motif is part of a protein interaction pocket that mediates interaction with cellular and viral proteins. http://togogenome.org/gene/10090:Kti12 ^@ http://purl.uniprot.org/uniprot/Q9D1R2 ^@ Similarity ^@ Belongs to the KTI12 family. http://togogenome.org/gene/10090:Bub1b ^@ http://purl.uniprot.org/uniprot/Q9Z1S0 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-243 regulates its degradation and timing in anaphase entry.|||Autophosphorylated in vitro. Intramolecular autophosphorylation stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-659 and Ser-1033 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.|||Cytoplasm|||Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen.|||Essential component of the mitotic checkpoint. Required for normal mitosis progression and tumor suppression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. Essential for tumor suppression. May play a role in regulating aging and fertility (By similarity).|||Highly expressed in thymus followed by spleen.|||Interacts with CENPE (PubMed:12925705). Interacts with PLK1 (By similarity). Part of a complex containing BUB3, CDC20 and BUB1B (By similarity). Interacts with anaphase-promoting complex/cyclosome (APC/C) (By similarity). Interacts with KNL1 (By similarity). Interacts with KAT2B (By similarity). Interacts with RIPK3 (By similarity). Interacts with the closed conformation form of MAD2L1 (By similarity). Interacts with CDC20 (By similarity).|||Kinase activity stimulated by CENPE.|||Mice die in utero.|||Nucleus|||Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The cleavage might be involved in the durability of the cell cycle delay.|||Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore (By similarity).|||The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.|||The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase.|||Ubiquitinated. Degraded by the proteasome (By similarity).|||kinetochore http://togogenome.org/gene/10090:Gadd45b ^@ http://purl.uniprot.org/uniprot/P22339 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GADD45 family.|||By cytokines.|||In myeloid precursor enriched BM cells.|||Interacts with GADD45GIP1.|||Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK (By similarity). http://togogenome.org/gene/10090:Clip3 ^@ http://purl.uniprot.org/uniprot/B9EHT4 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Functions as a cytoplasmic linker protein. Involved in TGN-endosome dynamics. May modulate the cellular compartmentalization of AKT kinase family and promote its cell membrane localization, thereby playing a role in glucose transport in adipocytes (By similarity).|||Golgi stack|||Homodimer. Interacts with AKT1 and AKT2; when AKT1 and AKT2 are phosphorylated and activated, affinity is higher for AKT2 (By similarity). Interacts with ZDHHC13 (via ANK repeats) (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:26198635).|||Microtubule association is inhibited by the ANK repeats and the Golgi localization region (GoLD).|||Palmitoylation by ZDHHC17 regulates association with the plasma membrane.|||The N-terminal half is dispensable for proper Golgi targeting, whereas the GoLD region is required. http://togogenome.org/gene/10090:Npffr1 ^@ http://purl.uniprot.org/uniprot/E9Q468 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Defb39 ^@ http://purl.uniprot.org/uniprot/Q70KL3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Only expressed in epididymis (caput, corpus and cauda).|||Secreted http://togogenome.org/gene/10090:Prrc1 ^@ http://purl.uniprot.org/uniprot/Q3UPH1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PRRC1 family.|||Golgi apparatus http://togogenome.org/gene/10090:Fam110b ^@ http://purl.uniprot.org/uniprot/Q8C739 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM110 family.|||Cytoplasm|||centrosome http://togogenome.org/gene/10090:Cstdc2 ^@ http://purl.uniprot.org/uniprot/Q9D264 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cystatin family.|||Secreted http://togogenome.org/gene/10090:Rnase4 ^@ http://purl.uniprot.org/uniprot/Q8C7E4 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Ppm1k ^@ http://purl.uniprot.org/uniprot/B9EHW0|||http://purl.uniprot.org/uniprot/Q8BXN7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PP2C family.|||Binds 1 Mg(2+) or Mn(2+) ion per subunit.|||Highly expressed in the heart, kidney, brain and liver and to a lesser extent in testis, lung, spleen and adipose tissue. Very low amount in muscle (at protein level). Also expressed in the thymus (at protein level) and the diaphragm. Significantly reduced in hypertrophied hearts.|||Mitochondrion matrix|||Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development. http://togogenome.org/gene/10090:Kremen1 ^@ http://purl.uniprot.org/uniprot/Q99N43 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals with a double knockout of KREM1 and KREM2 exhibit enhanced Wnt signaling accompanied by ectopic postaxial forelimb digits and expanded apical ectodermal ridges. They also exhibit increased bone volume and bone formation rates. Triple knockout mice KREM1/KREM2/DKK1 exhibit enhanced growth of ectopic digits.|||Cell membrane|||Expressed in the developing cochlea. Expressed first in the prosensory domain and the expression is restricted to supporting cells as development proceeds (at protein level). In the embryo, expression is first detected on day 9 and increases up to day 18. Lower levels are found in adult. At 9.5 dpc, expression is localized to the apical ectodermal ridge (AER) of the developing fore- and hindlimb buds, the telencephalon and the first brachial arch. At 10.5 dpc, expression is also observed in the myotome and in sensory tissues such as the nasal pit and optic vesicle. Expressed in the developing brain and developing limb buds.|||Forms a ternary complex with DKK1 and LRP6 (PubMed:12050670). Interacts with LRP6 in a DKK1-dependent manner. Interacts with DKK1 and RSPO1 (via FU repeats) (By similarity).|||In the adult, widely expressed with high levels in heart, lung, kidney, skeletal muscle and testis.|||Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6 (PubMed:12050670). In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane (By similarity). Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1 (PubMed:26206087). Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation (PubMed:18505822). Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification (PubMed:27550540). http://togogenome.org/gene/10090:Smpd2 ^@ http://purl.uniprot.org/uniprot/O70572 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by arachidonic acid.|||Although widely expressed in all tissues examined, except the spleen, high enzymatic activity occurs only in the brain.|||Belongs to the neutral sphingomyelinase family.|||Catalyzes, at least in vitro, the hydrolysis of sphingomyelin to form ceramide and phosphocholine (PubMed:9520418). Also hydrolyzes 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-platelet-activating factor) in vivo (By similarity). Also acts on 1-acyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PC) and sphingosylphosphocholine (By similarity).|||Cell membrane|||Mice lacking Smpd2 and Smpd3 are completely devoid of neutral SMase activity but do not developed sphingomyelin storage abnormalities. http://togogenome.org/gene/10090:Rasl11b ^@ http://purl.uniprot.org/uniprot/Q922H7 ^@ Similarity ^@ Belongs to the small GTPase superfamily. Ras family. http://togogenome.org/gene/10090:Naa40 ^@ http://purl.uniprot.org/uniprot/Q8VE10 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the acetyltransferase family. NAA40 subfamily.|||Cytoplasm|||Liver-specific knockout male mice have decreased body mass and are protected from age-associated hepatic steatosis. Male mice show a reduction in the liver triglyceride and free fatty acid levels. No effect on liver cholesterol level, liver weight, and liver function is observed.|||N-alpha-acetyltransferase that specifically mediates the acetylation of the N-terminal residues of histones H4 and H2A (By similarity). In contrast to other N-alpha-acetyltransferase, has a very specific selectivity for histones H4 and H2A N-terminus and specifically recognizes the 'Ser-Gly-Arg-Gly sequence' (By similarity). Acts as a negative regulator of apoptosis (By similarity). May play a role in hepatic lipid metabolism (PubMed:22231784).|||Nucleus http://togogenome.org/gene/10090:Ddx51 ^@ http://purl.uniprot.org/uniprot/Q6P9R1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ ATP-binding RNA helicase involved in the biogenesis of 60S ribosomal subunits.|||Belongs to the DEAD box helicase family. DDX51/DBP6 subfamily.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.|||nucleolus http://togogenome.org/gene/10090:Rbak ^@ http://purl.uniprot.org/uniprot/Q8BQC8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with AR (By similarity). May also interact with other nuclear hormone receptors such as NR3C1/GR (By similarity). Interacts with RB1.|||May repress E2F-dependent transcription. May promote AR-dependent transcription.|||Nucleus http://togogenome.org/gene/10090:P4htm ^@ http://purl.uniprot.org/uniprot/Q8BG58 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Fe(2+) ion per subunit.|||Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Endoplasmic reticulum membrane|||Glycosylated.|||Highest expression levels are detected in the eye and brain, especially in the retinal epithelium cells and cortical neurons. Also expressed in skeletal muscle, lung, heart, adrenal gland, kidney, prostate, thyroid and testis.|||Homodimer.|||Mutant mice exhibit inflammation and fibrosis of renal tubuli, glomerular sclerosis, enlarged Bowman capsules, and develop late-onset proteinuria. Vision is compromised, primarily due to impairment of cone function. http://togogenome.org/gene/10090:Or6z5 ^@ http://purl.uniprot.org/uniprot/Q8VGH6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Trpt1 ^@ http://purl.uniprot.org/uniprot/Q8K3A2 ^@ Function|||Similarity ^@ Belongs to the KptA/TPT1 family.|||Catalyzes the last step of tRNA splicing, the transfer of the splice junction 2'-phosphate from ligated tRNA to NAD to produce ADP-ribose 1''-2'' cyclic phosphate. http://togogenome.org/gene/10090:Il1rl1 ^@ http://purl.uniprot.org/uniprot/P14719 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the interleukin-1 receptor family.|||Cell membrane|||Expressed first in the fetal liver and then in lung and hematopoietic tissues.|||In response to cardiotoxin-induced muscle injury, mutant mice show impaired inflammation resolution characterized by deficient muscle fiber regeneration and impaired clearance of necrotic cells.|||Inhibits IL-33 signaling.|||Interacts with MYD88, IRAK1, IRAK4, and TRAF6 (By similarity). Bound to its ligand IL33, interacts with IL1RAP to form the minimal interleukin-33 signaling complex with a 1:1:1 stoichiometry. Interacts with KIT (bound to KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88. Interacts with TMED1.|||Phosphorylated by GSK3B at Ser-442; leading to proteasomal degradation.|||Predominantly expressed in hematopoietic tissues, and in macrophage, erythroid, epithelial and fibroblast cell lines. Isoform A is expressed in brain astrocytes and microglia. Isoform B is expressed in brain endothelial cells.|||Receptor for interleukin-33 (IL-33) which plays crucial roles in innate and adaptive immunity, contributing to tissue homeostasis and responses to environmental stresses together with coreceptor IL1RAP (PubMed:18450470, PubMed:17675517, PubMed:29045903, PubMed:22660580). Its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8 (By similarity). Possibly involved in helper T-cell function (By similarity). Upon tissue injury, induces UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (PubMed:34644537).|||Secreted|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.|||Ubiquitinated at Lys-326 in a FBXL19-mediated manner; leading to proteasomal degradation (PubMed:22660580). Ubiquitination by TRAF6 via 'Lys-27'-linked polyubiquitination and deubiquitination by USP38 serves as a critical regulatory mechanism for fine-tuning IL1RL1-mediated inflammatory response (By similarity). http://togogenome.org/gene/10090:Fam177a2 ^@ http://purl.uniprot.org/uniprot/Q8BR63 ^@ Similarity ^@ Belongs to the FAM177 family. http://togogenome.org/gene/10090:Riox2 ^@ http://purl.uniprot.org/uniprot/Q8CD15 ^@ Cofactor|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ROX family. MINA53 subfamily.|||Binds 1 Fe(2+) ion per subunit.|||In testis, expressed in the nuclei of spermatogonia at all stages of the seminiferous epithelial cycle, and in meiotic prophase cells such as preleptotene, leptotene and zygotene, and weakly in early pachytene spermatocytes, but is absent in late pachytene spermatocytes, spermatids and mature sperm (at protein level).|||Nucleus|||Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Is involved in the demethylation of trimethylated 'Lys-9' on histone H3 (H3K9me3), leading to an increase in ribosomal RNA expression. Also catalyzes the hydroxylation of 60S ribosomal protein L27a on 'His-39' (By similarity). May play an important role in cell growth and survival. May be involved in ribosome biogenesis, most likely during the assembly process of pre-ribosomal particles.|||Predominantly expressed in testis. Expressed at high levels in spleen, thymus, and colon, but barely detectable in brain, skeletal muscle, and seminal vesicle (at protein level).|||Up-regulated in experimentally-induced cryptorchid testis.|||nucleolus http://togogenome.org/gene/10090:Bub3 ^@ http://purl.uniprot.org/uniprot/Q9WVA3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat BUB3 family.|||Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (APC/C) when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1 (By similarity). Regulates chromosome segregation during oocyte meiosis.|||Interacts with BUB1 and BUBR1. The BUB1/BUB3 complex interacts with MAD1L1. Interacts with ZNF207/BuGZ; leading to promote stability and kinetochore loading of BUB3 (By similarity).|||Nucleus|||Poly-ADP-ribosylated by PARP1.|||kinetochore http://togogenome.org/gene/10090:Rassf7 ^@ http://purl.uniprot.org/uniprot/Q9DD19 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with MAP2K7 and GTP-bound NRAS.|||Negatively regulates stress-induced JNK activation and apoptosis by promoting MAP2K7 phosphorylation and inhibiting its ability to activate JNK. Following prolonged stress, anti-apoptotic effect stops because of degradation of RASSF7 protein via the ubiquitin-proteasome pathway. Required for the activation of AURKB and chromosomal congression during mitosis where it stimulates microtubule polymerization (By similarity).|||Polyubiquitinated and degraded by the proteasome upon prolonged stress stimuli.|||centrosome http://togogenome.org/gene/10090:Znhit3 ^@ http://purl.uniprot.org/uniprot/Q9CQK1 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in proliferating fetal granule cell precursors at embryonic day 16.5, in proliferating and post-mitotic granule cells at postnatal days 3 and 10. Expression in cerebellar Purkinje cells is strong at postnatal days 10 and 21.|||Expressed in the cerebellum.|||Nucleus|||Thyroid receptor interacting proteins (TRIPs) specifically interact with the ligand binding domain of the thyroid receptor (TR) (By similarity). Requires the presence of thyroid hormone for its interaction (By similarity). Interacts with NUFIP1 (By similarity). Interacts (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the presence of ADP (By similarity). http://togogenome.org/gene/10090:Large1 ^@ http://purl.uniprot.org/uniprot/Q9Z1M7 ^@ Cofactor|||Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity (PubMed:23125099, PubMed:23135544, PubMed:25138275, PubMed:32975514). Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (By similarity). Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide primer (PubMed:32975514). Plays a key role in skeletal muscle function and regeneration (PubMed:15184894, PubMed:24132234).|||Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn(2+).|||Defects in Large are the cause of myodystrophy (myd), an autosomal recessive neuromuscular phenotype, probably due to abnormal post-translational modification of alpha-dystroglycan.|||Golgi apparatus membrane|||In the C-terminal section; belongs to the glycosyltransferase 49 family.|||In the N-terminal section; belongs to the glycosyltransferase 8 family.|||Interacts with DAG1 (via the N-terminal domain of alpha-DAG1); the interaction increases binding of DAG1 to laminin (PubMed:15210115). Interacts with B4GAT1.|||Ubiquitous. Highest expression in heart, diaphragm and brain, where it is especially found in cerebral cortex, hippocampus, and trigeminal ganglion.|||Ubiquitously found at 14.5 dpc with strong expression in heart, central nervous system structures such as cerebral cortex, hippocampus, olfactory lobe, trigeminal ganglion and spinal cord. Also expressed in diaphragm and duodenum. http://togogenome.org/gene/10090:Mylip ^@ http://purl.uniprot.org/uniprot/Q8BM54 ^@ Activity Regulation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity.|||Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.|||Expressed in liver, spleen, intestine and adrenals.|||Homodimer. Interacts with the E2 ubiquitin-conjugating enzyme, UBE2D1 (via RING-type zinc finger). Interacts with myosin regulatory light chain (MRLC) and TMEM4.|||The FERM domain binds phospholipids and mediates lipoprotein receptors recognition at the plasma membrane through their cytoplasmic tails.|||The RING domain mediates ubiquitination and the neurite outgrowth inhibitory activity.|||The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes. http://togogenome.org/gene/10090:Ppp1cc ^@ http://purl.uniprot.org/uniprot/P63087|||http://purl.uniprot.org/uniprot/Q6ZWM8 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PPP phosphatase family. PP-1 subfamily.|||Binds 2 manganese ions per subunit.|||Cleavage furrow|||Cytoplasm|||Deficient mice exhibit male infertility due to severely impaired spermiogenesis beginning at the round spermatid stage. Females are fertile.|||Inactivated by binding to URI1.|||Isoform 1 is widely expressed (PubMed:9339378). Isoform 2 is highly enriched in testis, mainly restricted to meiotic and postmeiotic germ cells (PubMed:9339378).|||Midbody|||Mitochondrion|||Nucleus|||Nucleus speckle|||PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R3B, PPP1R7 and CDCA2 (By similarity). Isoform 2 interacts with SPZ1. This interaction can prevent SPZ1 binding to the E-box and inhibits PPP1CC activity. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with IKFZ1; the interaction targets PPP1CC to pericentromeric heterochromatin, dephosphorylates IKAROS, stabilizes it and prevents it from degradation. Interacts with NOM1 and PPP1R8. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with NEK2. Interacts with NEK2. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner (By similarity). Isoform 2 interacts with PPP1R42; the interaction is direct. Interacts with FOXP3 (By similarity). Isoform 2 interacts with TMEM225 (via RVxF motif) (PubMed:25605614). Isoform 2, but not isoform 1, interacts with Sh3glb1 testis-specific isoform 3; this interaction leads to the inhibition of phosphatase activity (PubMed:17381077). Interacts with MKI67 (By similarity). Interacts with RRP1B; this targets PPP1CC to the nucleolus (By similarity). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity) (PubMed:14638860, PubMed:15226296, PubMed:16835242, PubMed:17381077, PubMed:19282287, PubMed:19886865, PubMed:25605614). Interacts with DYNLT4 (By similarity). Interacts (via RVxF motif) with FIRRM; regulates PLK1 kinase activity (By similarity).|||Phosphorylated by NEK2.|||Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E.|||Required for normal male fertility.|||kinetochore|||microtubule organizing center|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Acadl ^@ http://purl.uniprot.org/uniprot/A0A0R4J083|||http://purl.uniprot.org/uniprot/P51174 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acadl deficiency results in significant gestational loss of embryos (PubMed:9861014). Homozygous knockout mice that achieve birth display severe fasting intolerance with subsequent hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, non-ketotic dicarboxylic aciduria, and myocardial degeneration (PubMed:9861014).|||Acetylation at Lys-318 and Lys-322 in proximity of the cofactor-binding sites strongly reduces catalytic activity. These sites are deacetylated by SIRT3.|||Belongs to the acyl-CoA dehydrogenase family.|||Expressed in heart, skeletal muscle, kidney, and brain (PubMed:9861014). Expressed in liver (at protein level) (PubMed:9861014).|||Homotetramer.|||Long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats. The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (By similarity). Among the different mitochondrial acyl-CoA dehydrogenases, long-chain specific acyl-CoA dehydrogenase can act on saturated and unsaturated acyl-CoAs with 6 to 24 carbons with a preference for 8 to 18 carbons long primary chains (PubMed:9861014).|||Mitochondrion matrix http://togogenome.org/gene/10090:Pfkfb4 ^@ http://purl.uniprot.org/uniprot/C9VZF2|||http://purl.uniprot.org/uniprot/Q6DTY7 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Homodimer.|||In the C-terminal section; belongs to the phosphoglycerate mutase family.|||Synthesis and degradation of fructose 2,6-bisphosphate.|||The most important regulatory mechanism of these opposing activities is by phosphorylation and dephosphorylation of the enzyme. http://togogenome.org/gene/10090:Ebag9 ^@ http://purl.uniprot.org/uniprot/Q9D0V7 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By 17-beta-estradiol (E2).|||Expressed in the developing embryo.|||Golgi apparatus membrane|||Homodimer.|||May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.|||The coiled coil domain is necessary for the homodimerization.|||Widely expressed. Expressed in heart, brain, spleen, liver, kidney and testis. http://togogenome.org/gene/10090:Pramel24 ^@ http://purl.uniprot.org/uniprot/A2AGW8 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Cacna1a ^@ http://purl.uniprot.org/uniprot/A0A571BET0|||http://purl.uniprot.org/uniprot/E9Q1R5|||http://purl.uniprot.org/uniprot/P97445|||http://purl.uniprot.org/uniprot/Q3UHA5|||http://purl.uniprot.org/uniprot/Q3UHN4|||http://purl.uniprot.org/uniprot/Q8R5M6|||http://purl.uniprot.org/uniprot/Q8R5M7 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.|||Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1A subfamily.|||Brain specific; mainly found in the cerebellum, olfactory bulb, cerebral cortex, hippocampus, and inferior colliculus. In the hippocampus, expression occurs in pyramidal and granule neurons, as well as in interneurons. Purkinje cells contain predominantly P-type VSCC, the Q-type being a prominent calcium current in cerebellar granule cells.|||Cell membrane|||Defects in Cacna1a are the cause of a delayed-onset, recessive neurological disorder seen in tottering (tg) mutants, resulting in ataxia, motor seizures and behavioral absence seizures resembling petit mal epilepsy (or absence epilepsy) in humans. There are two more alleles, leaner (tg(lA)), that is characterized by severe ataxia and frequent death past weaning, but no motor seizures; and rolling Nagoya (tg(rol)), that presents an intermediary phenotype, the ataxia being somewhat more severe that with tg, but without motors seizures. Selective degeneration of cerebellar Purkinje cells has been shown for all these types of mutants. Selective degeneration of cerebellar Purkinje cells has been shown for all these types of mutants.|||Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.|||Membrane|||Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interacts with CABP1 (By similarity).Interacts with the spider omega-agatoxin-IVA (AC P30288) (By similarity).|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents.|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity). They are however insensitive to dihydropyridines (DHP). http://togogenome.org/gene/10090:Slx ^@ http://purl.uniprot.org/uniprot/D3Z347 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Vim ^@ http://purl.uniprot.org/uniprot/P20152|||http://purl.uniprot.org/uniprot/Q5FWJ3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cell membrane|||Cytoplasm|||Detected in eye lens fiber cells (at protein level) (PubMed:15037121, PubMed:14985306, PubMed:19029034, PubMed:21745462, PubMed:27559293). Expressed in retinal lens epithelial cells (at protein level) (PubMed:27559293). Expressed in Langerhans cells in the epidermis (at protein level) (PubMed:19267394).|||Expressed in the cytoplasm of anterior lens epithelial cells, expression becomes predominantly membranous as lens fiber cell differentiation progresses at 3 weeks of age.|||Homomer assembled from elementary dimers (By similarity). Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin (PubMed:21745462). Interacts with BCAS3 (By similarity). Interacts with LGSN (PubMed:18178558). Interacts with SYNM (PubMed:17356066). Interacts (via rod region) with PLEC (via CH 1 domain) (PubMed:15128297). Interacts with PLEC isoform 1C (PubMed:24940650). Interacts with STK33 (By similarity). Interacts with LARP6 (By similarity). Interacts with RAB8B (By similarity). Interacts with TOR1A; the interaction associates TOR1A with the cytoskeleton (PubMed:18827015). Interacts with TOR1AIP1 (By similarity). Interacts with DIAPH1 (By similarity). Interacts with EPPK1; interaction is dependent of higher-order structure of intermediate filament (By similarity). Interacts with the non-receptor tyrosine kinase SRMS; the interaction leads to phosphorylation of VIM (By similarity). Interacts with NOD2 (By similarity). Interacts (via head region) with CORO1C (PubMed:27178841). Interacts with HDGF (By similarity). Interacts with PRKCE (via phorbol-ester/DAG-type 2 domain) (By similarity). Interacts with BFSP2 (PubMed:19029034). Interacts with PPL (PubMed:19029034). Interacts with PKP1 and PKP2 (By similarity).|||Involved with LARP6 in the stabilization of type I collagen mRNAs for CO1A1 and CO1A2.|||Morphological change from tubular conformation to circular conformation of beaded filament structures in retinal lens epithelium, potentially due to loss of contacts with surrounding intermediate filaments (PubMed:27559293). BFSP2 and VIM double knockout mice show a complete loss of cytoplasmic cytoskeleton in retinal lens fiber cells (PubMed:15037121).|||Nucleus matrix|||Phosphorylation by PKN1 inhibits the formation of filaments. Filament disassembly during mitosis is promoted by phosphorylation at Ser-55 as well as by nestin. One of the most prominent phosphoproteins in various cells of mesenchymal origin. Phosphorylation is enhanced during cell division, at which time vimentin filaments are significantly reorganized. Phosphorylated at Ser-56 by CDK5 during neutrophil secretion in the cytoplasm. Phosphorylated by STK33. Phosphorylated on tyrosine residues by SRMS.|||S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.|||The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.|||The central alpha-helical coiled-coil IF rod domain mediates elementary homodimerization.|||Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally.|||cytoskeleton http://togogenome.org/gene/10090:Itpr1 ^@ http://purl.uniprot.org/uniprot/P11881|||http://purl.uniprot.org/uniprot/Q3UVA1|||http://purl.uniprot.org/uniprot/Q8BQN0|||http://purl.uniprot.org/uniprot/Q8C7X9 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the InsP3 receptor family.|||Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor.|||Endoplasmic reticulum membrane|||Homotetramer.|||Homotetramer. Interacts with TRPC4. The PPXXF motif binds HOM1, HOM2 and HOM3. Interacts with RYR1, RYR2, ITPR1, SHANK1 and SHANK3. Interacts with ERP44 in a pH-, redox state- and calcium-dependent manner which results in the inhibition the calcium channel activity. The strength of this interaction inversely correlates with calcium concentration. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1 (PubMed:16990611). Interacts with CABP1 (via N-terminus) (By similarity). Interacts with TESPA1. Interacts (when not phosphorylated) with AHCYL1 (when phosphorylated); the interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1 and is increased in the presence of BCL2L10 (PubMed:23542070). Interacts with AHCYL2 (with lower affinity than with AHCYL1) (By similarity). Interacts with BCL2L10; the interaction is increased in the presence of AHCLY1 (By similarity). Interacts with BOK (via BH4 domain); protects ITPR1 from proteolysis by CASP3 during apoptosis (PubMed:23884412).|||Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5-trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (PubMed:23542070). Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways.|||Palmitoylated by ZDHHC6 in immune cells, leading to regulation of ITPR1 stability and function (PubMed:25368151).|||Phosphorylated by cAMP kinase (PKA). Phosphorylation prevents the ligand-induced opening of the calcium channels. Phosphorylation by PKA increases the interaction with inositol 1,4,5-trisphosphate and decreases the interaction with AHCYL1.|||Phosphorylated on tyrosine residues.|||Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.|||The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.|||Ubiquitination at multiple lysines targets ITPR1 for proteasomal degradation. Approximately 40% of the ITPR1-associated ubiquitin is monoubiquitin, and polyubiquitins are both 'Lys-48'- and 'Lys-63'-linked (By similarity).|||perinuclear region|||secretory vesicle membrane http://togogenome.org/gene/10090:Card11 ^@ http://purl.uniprot.org/uniprot/Q8CIS0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement (PubMed:12356734, PubMed:12154356, PubMed:16356855). Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:12356734, PubMed:12154356, PubMed:16356855). Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation (By similarity). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (By similarity). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (By similarity). Stimulates the phosphorylation of BCL10 (By similarity). Also activates the TORC1 signaling pathway (By similarity).|||Cytoplasm|||Homodimer; disulfide-linked (By similarity). Homomultimer; polymerizes following activation, forming a nucleating helical template that seeds BCL10-filament formation via a CARD-CARD interaction (By similarity). Interacts (via CARD domain) with BCL10 (via CARD domain); interaction takes place following CARD11 activation and polymerization, leading to the formation of a filamentous CBM complex assembly (PubMed:22880103). Component of a CBM complex (CARD11-BCL10-MALT1) complex involved in NF-kappa-B activation (By similarity). Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (By similarity). Interacts (via PDZ domain) with DPP4 (via cytoplasmic tail) (By similarity).|||Impaired activation of NF-kappa-B downstream of T-cell receptor (TCR), leading to defects in interleukin-2 (IL2) production.|||Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (By similarity). Activation downstream of T-cell receptor (TCR) by phosphorylation by PRKCB and PRKCQ triggers CARD11 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B (PubMed:16356855).|||Membrane raft|||Phosphorylation at Ser-564, Ser-649 and Ser-657 by PRKCB and PRKCQ leads to a shift from an inactive to an active form that activates the NF-kappa-B signaling.|||The linker region, also named autoinhibitory interface, is less inhibitory on its own than that of CARD9. The linker region together with the inhibitory domain (ID) are required to prevent constitutive activation and maintain CARD11 in an autoinhibitory state. Disruption of the inhibitory domain (ID) region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments. http://togogenome.org/gene/10090:Cd9 ^@ http://purl.uniprot.org/uniprot/P40240 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Expressed predominantly in the peripheral nervous system (PubMed:14715942). Highly expressed in oocytes and blastocysts (at protein level) (PubMed:10518536, PubMed:10634790, PubMed:10634791, PubMed:23213457). Expression is also observed on follicular oocytes in the ovary, whereas no expression is found on follicular cells (at protein level) (PubMed:10518536, PubMed:10634790). Expressed in skeletal muscle mainly in endothelial cells of endomysial capillaries, in satellite cells and myoblasts (at protein level).|||Forms both disulfide-linked homodimers and higher homooligomers as well as heterooligomers with other members of the tetraspanin family (By similarity). Interacts (via the second extracellular domain) with integrin ITGAV:ITGB3 (By similarity). Interacts with integrin ITGA6:ITGB1; interaction takes place in oocytes and is involved in sperm-egg fusion (PubMed:10634791). Part of integrin-tetraspanin complexes composed of CD81, beta-1 and beta-2 integrins in the membrane of monocyte/macrophages (By similarity). Interacts with CD63; identified in a complex with CD63 and ITGB3 (By similarity). Associates with CR2/CD21 and with PTGFRN/CD9P1 (By similarity). Part of a complex composed of CD9, CD81, PTGFRN and IGSF8 (PubMed:23575678). Interacts directly with IGSF8 (By similarity). Interacts with PDPN; this interaction is homophilic and attenuates platelet aggregation and pulmonary metastasis induced by PDPN (By similarity).|||Integral membrane protein associated with integrins, which regulates different processes, such as sperm-egg fusion, platelet activation and aggregation, and cell adhesion (PubMed:10700183, PubMed:10634790, PubMed:10634791, PubMed:14715942). Present at the cell surface of oocytes and plays a key role in sperm-egg fusion, possibly by organizing multiprotein complexes and the morphology of the membrane required for the fusion (PubMed:10700183, PubMed:10634790, PubMed:10634791, PubMed:21690351). In myoblasts, associates with CD81 and PTGFRN and inhibits myotube fusion during muscle regeneration (PubMed:23575678). In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles. Also prevents the fusion between mononuclear cell progenitors into osteoclasts in charge of bone resorption (PubMed:12796480). Acts as a receptor for PSG17 (PubMed:11805154). Involved in platelet activation and aggregation (PubMed:14715942). Regulates paranodal junction formation (PubMed:14715942). Involved in cell adhesion, cell motility and tumor metastasis (By similarity). Also regulates integrin-dependent migration of macrophages, particularly relevant for inflammatory response in the lung (PubMed:18662991).|||Knockout mice are healthy, but females display severely reduced fertility (PubMed:10634790, PubMed:10634791). Oocyte maturation and ovulation are normal and female infertility is caused by defects in sperm-egg fusion (PubMed:10634790, PubMed:10634791). Wild type sperm penetrates the zona pellucida, binds to the oolema but the membranes fail to fuse (PubMed:10634790, PubMed:10634791). The infertility is overcome by intracytoplasmic sperm injection, and embryos develop normally (PubMed:10634790, PubMed:10634791). Eggs show reduced ability for strong sperm adhesion, and sperm accumulate in the perivitelline space, only transiently binding to the egg surface (PubMed:21690351). In response to notexin-induced acute myoinjury, mutant mice display abnormal muscle regeneration characterized by typical giant distrophic myofibres (PubMed:23575678). These mice spontaneously develop multinucleated giant cells (MGCs) and show enhanced osteoclastogenesis when compared to wild-type littermates (PubMed:12796480). CD81 and CD9 double knockout mice develop pulmonary emphysema, reminiscent of chronic obstructive pulmonary disease in human (PubMed:18662991).|||Membrane|||Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro). The protein exists in three forms with molecular masses between 22 and 27 kDa, and is known to carry covalently linked fatty acids. Palmitoylation by ZDHHC2 regulates CD9 expression, association with other tetraspanin family proteins and function in cell adhesion.|||extracellular exosome http://togogenome.org/gene/10090:Cyld ^@ http://purl.uniprot.org/uniprot/A0A1B0GSE5|||http://purl.uniprot.org/uniprot/Q80TQ2 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Cell membrane|||Cytoplasm|||Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis (PubMed:17548520, PubMed:28701375, PubMed:29291351, PubMed:32185393, PubMed:32424362). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:16713561). Contributes to the regulation of cell survival, proliferation and differentiation via its effects on NF-kappa-B activation (PubMed:16713561). Negative regulator of Wnt signaling. Inhibits HDAC6 and thereby promotes acetylation of alpha-tubulin and stabilization of microtubules (PubMed:19893491). Plays a role in the regulation of microtubule dynamics, and thereby contributes to the regulation of cell proliferation, cell polarization, cell migration, and angiogenesis (PubMed:16713561, PubMed:20194890, PubMed:19893491). Required for normal cell cycle progress and normal cytokinesis (PubMed:19893491). Inhibits nuclear translocation of NF-kappa-B (By similarity). Plays a role in the regulation of inflammation and the innate immune response, via its effects on NF-kappa-B activation (By similarity). Dispensable for the maturation of intrathymic natural killer cells, but required for the continued survival of immature natural killer cells (PubMed:16501569, PubMed:18643924). Negatively regulates TNFRSF11A signaling and osteoclastogenesis (PubMed:18382763). Involved in the regulation of ciliogenesis, allowing ciliary basal bodies to migrate and dock to the plasma membrane; this process does not depend on NF-kappa-B activation (PubMed:25134987). Ability to remove linear ('Met-1'-linked) polyubiquitin chains regulates innate immunity and TNF-alpha-induced necroptosis: recruited to the LUBAC complex via interaction with SPATA2 and restricts linear polyubiquitin formation on target proteins (PubMed:28701375). Regulates innate immunity by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation (By similarity). Involved in TNF-alpha-induced necroptosis by removing linear ('Met-1'-linked) polyubiquitin chains from RIPK1, thereby regulating the kinase activity of RIPK1 (PubMed:28701375). Negatively regulates intestinal inflammation by removing 'Lys-63' linked polyubiquitin chain of NLRP6, thereby reducing the interaction between NLRP6 and PYCARD/ASC and formation of the NLRP6 inflammasome (PubMed:32424362). Removes 'Lys-63' linked polyubiquitin chain of MAP3K7, which inhibits phosphorylation and blocks downstream activation of the JNK-p38 kinase cascades (PubMed:17548520, PubMed:29291351). Removes also 'Lys-63'-linked polyubiquitin chains of MAP3K1 and MA3P3K3, which inhibit their interaction with MAP2K1 and MAP2K2 (By similarity).|||Interacts (via CAP-Gly domain) with IKBKG/NEMO (via proline-rich C-terminal region) (By similarity). Interacts with TRAF2 and TRIP (By similarity). Interacts with PLK1, DVL1, DVL3, MAVS, TBK1, IKKE and RIGI (By similarity). Interacts (via CAP-Gly domain) with microtubules (PubMed:19893491). Interacts with HDAC6 and BCL3 (PubMed:16713561, PubMed:19893491). Interacts with MAP3K7 (PubMed:17548520). Identified in a complex with TRAF6 and SQSTM1 (PubMed:18382763). Interacts with OPTN and SQSTM1 (By similarity). Interacts with CEP350 (By similarity). Interacts with RNF31; the interaction is indirect and is mediated via SPATA2 (By similarity). Interacts with SPATA2 (via the PUB domain); the interaction is direct and recruits CYLD to the LUBAC complex, thereby regulating TNF-alpha-induced necroptosis (By similarity).|||Membrane|||No obvious phenotype, but mice are highly susceptible to carcinogens and are prone to chemically induced skin tumors (PubMed:16501569, PubMed:16713561, PubMed:17548520, PubMed:18382763, PubMed:18643924). The number of natural killer T-cells is much reduced (PubMed:16501569, PubMed:16713561, PubMed:17548520, PubMed:18382763, PubMed:18643924). Animals are highly susceptible to bacteria-induced pneumonia, due to an over active innate immune response (PubMed:16501569, PubMed:16713561, PubMed:17548520, PubMed:18382763, PubMed:18643924). Mice are more susceptible to C.rodentium infection, leading to severe inflammation in the intestine (PubMed:32424362). Animals spontaneously develop colonic inflammation, due to constitutive expression of several pro-inflammatory genes in the colon (PubMed:16501569, PubMed:16713561, PubMed:17548520, PubMed:18382763, PubMed:18643924). Animals exhibit abnormal osteoclast differentiation, leading to osteoporosis (PubMed:16501569, PubMed:16713561, PubMed:17548520, PubMed:18382763, PubMed:18643924). Hepatocyte-specific knockout mice do not exhibit any liver-related pathological phenotype under unstressed conditions (PubMed:29291351). In response to a 24-week high fat dier, they exhibit higher body and liver weight as well as reduced glucose tolerance and insulin resistance compared to controls (PubMed:29291351). They also show a considerable inflammatory response, including elevation of cytokine and chemokine concentrations in serum and mRNA expression in liver (PubMed:29291351).|||Phosphorylated on several serine residues by IKKA and/or IKKB in response to immune stimuli. Phosphorylation requires IKBKG. Phosphorylation abolishes TRAF2 deubiquitination, interferes with the activation of Jun kinases, and strongly reduces CD40-dependent gene activation by NF-kappa-B (By similarity).|||Ubiquitinated. Polyubiquitinated in hepatocytes treated with palmitic acid. Ubiquitination is mediated by E3 ligase TRIM47 and leads to proteasomal degradation.|||Up-regulated by TNFRSF11A.|||centrosome|||cilium basal body|||cytoskeleton|||perinuclear region|||spindle http://togogenome.org/gene/10090:Thap1 ^@ http://purl.uniprot.org/uniprot/Q8CHW1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the THAP1 family.|||DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. May also have pro-apoptotic activity by potentiating both serum-withdrawal and TNF-induced apoptosis (By similarity).|||Highest levels in heart, liver and kidney. Lower levels in brain and lung.|||Interacts with PAWR. Component of a THAP1/THAP3-HCFC1-OGT complex that contains, either THAP1 or THAP3, HCFC1 and OGT. Interacts with OGT. Interacts (via the HBM) with HCFC1 (via the Kelch-repeat domain); the interaction recruits HCFC1 to the RRM1 promoter (By similarity).|||PML body|||nucleoplasm http://togogenome.org/gene/10090:Lyzl1 ^@ http://purl.uniprot.org/uniprot/A0A077S9Z4|||http://purl.uniprot.org/uniprot/Q9CPX3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 22 family.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Scd1 ^@ http://purl.uniprot.org/uniprot/P13516|||http://purl.uniprot.org/uniprot/Q547C4 ^@ Cofactor|||Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family.|||Defects is Scd1 are the cause of asebia (ab) (PubMed:17738154, PubMed:10545940, PubMed:10854228, PubMed:10899171, PubMed:15278437). The trait is due to spontaneous autosomal recessive mutations that give rise to deletions or point mutations in Scd1. The ab trait has complete penetrance (PubMed:17738154). Ab mice are characterized by reduced body weight, extreme sebaceous gland hypoplasia leading to nearly complete absence of sebaceous glands, and thickened, scaly skin with hyperkeratosis and alopecia (PubMed:17738154, PubMed:10854228, PubMed:15278437). The hair follicles are abnormally long and extend at a sharp angle into the subcutis, probably due to abnormal persistence of inner root sheath. Frequently the hair shaft ruptures through the base of the hair follicle, giving rise to inflammation that results in scarring alopecia (PubMed:10854228, PubMed:15278437). Besides, ab mice display increased transepithelial water loss (PubMed:10854228). Ab mice present a narrow eye fissure and their eyes are nearly closed (PubMed:10854228, PubMed:15278437). Older mice develop blindness (PubMed:17738154). Scd1 activity is almost absent in liver, and is not compensated by expression of another family member (PubMed:10899171). Liver levels of total cholesterol esters are decreased by 87%, while plasma cholesterol levels are increased by 35% (PubMed:10899171). Likewise, skin sterol esters and diol diesters are strongly reduced (PubMed:10854228). Liver triglyceride levels are decreased by 62%, while plasma triglyceride levels are decreased by 67% (PubMed:10899171). The fatty acid composition of liver triglycerides is altered, with a decrease of about 85% in palmitoleate (C16:1) and oleate (C18:1) levels (PubMed:10899171). These defects cannot be compensated by a diet enriched in unsaturated fatty acids (PubMed:10899171, PubMed:11441127).|||Detected in liver (at protein level) (PubMed:10899171, PubMed:11533264). Detected in skin and liver (PubMed:10545940, PubMed:11161812, PubMed:11441127, PubMed:11533264). Detected in sebaceous gland, but not in hair follicle (PubMed:10545940). Detected in white and brown adipose tissue, eyelid, Harderian gland, and at lower levels in Meibomian gland, eyeball and adrenal gland (PubMed:11500518, PubMed:11533264). Highly expressed in liver, and detected at low levels in brain, heart, lung, stomach, skeletal muscle and kidney (PubMed:11161812, PubMed:12815040).|||Endoplasmic reticulum membrane|||Expected to bind 2 Fe(2+) ions per subunit, instead of the Zn(2+) ions seen in the 3D-structure.|||Membrane|||Mice are viable and fertile (PubMed:11533264). Compared to wild-type, they consume about 25% more food, but are leaner and acumulate less white adipose tissue (PubMed:12177411, PubMed:17127673). Their liver glycogen levels are lower than wild-type, except when their diet is supplemented with high levels of triolein (PubMed:17127673). They gain weight and accumulate white adipose tissue when their diet contains high levels of triolein (PubMed:17127673). They loose weight on a diet rich in tristearin, contrary to wild-type (PubMed:17127673). Mutant mice cannot maintain their body temperature when exposed to cold; they display hypoglycemia, depleted liver glycogen levels, and die of hypothermia (PubMed:15210843). Mutant mice display increased levels of mitochondrial fatty acid oxidation and decreased expression of genes that are important for de novo lipogenesis, especially when their diet is enriched in saturated fatty acids (PubMed:12177411, PubMed:17127673). Their brown adipose tissues shows increased lipolysis and fatty acid oxidation (PubMed:15210843). They display increased metabolic rates during the day and the night (PubMed:12177411). Liver, skin and white adipose tissue from mutant mice show strongly decreased levels of palmitoleate and reduced levels of oleate, with increased levels of saturated fatty acids (PubMed:11533264). Likewise, skin and eyelids are deficient in cholesterol esters, wax esters and triglycerides (PubMed:11533264). These defects cannot be compensated by a diet enriched in unsaturated fatty acids (PubMed:11533264). Mutant mice have decreased levels of liver and plasma triglycerides (PubMed:17127673). Likewise, the levels of triglycerides, 1,2-diacylglycerol and free fatty acids are decreased in the brown adipose tissue (PubMed:15210843). Besides, brown adipose tissue, liver and plasma triglycerides are depleted in unsaturated fatty acids and are enriched in saturated fatty acids (PubMed:15210843, PubMed:17127673). A diet enriched in triolein increases liver and plasma levels of triglycerides (PubMed:17127673). Mutant mice display lower fasting insulin levels, normal fasting glucose levels, increased glucose tolerance and increased insulin sensitivity (PubMed:12177411). Mutant mice display alopecia and atrophy of sebaceous glands and Meibomian glands (PubMed:11533264). Besides, they present a narrow eye fissure and their eyes are nearly closed (PubMed:11533264). This eye phenotype is probably due to a defect in the production of meibum, the oily material that prevents drying of the cornea. Scd1 activity is almost absent in liver, and is not compensated by expression of another family member (PubMed:11533264). Strongly reduced levels of lipids containing Delta-9 unsaturated fatty acids in the Harderian gland, leading to strongly reduced levels of 1-alkyl-2,3-diacylglycerol in the Harderian gland (PubMed:11500518).|||Microsome membrane|||Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the Delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA (PubMed:11500518, PubMed:11533264, PubMed:16275639, PubMed:16443825, PubMed:26098370). Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids (PubMed:11500518, PubMed:11533264, PubMed:16443825, PubMed:26098370). Plays an important role in lipid biosynthesis (PubMed:17127673, PubMed:10899171, PubMed:11500518, PubMed:11441127, PubMed:11533264, PubMed:12177411, PubMed:26098370). Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation (PubMed:12177411, PubMed:17127673, PubMed:24356954, PubMed:24295027). Plays an important role in body energy homeostasis (PubMed:17127673, PubMed:15210843, PubMed:24295027, PubMed:24356954). Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides (PubMed:10899171, PubMed:11500518, PubMed:11441127, PubMed:11533264, PubMed:12177411, PubMed:15210843, PubMed:26098370). Required for normal development of sebaceous glands (PubMed:17738154, PubMed:11533264). Required for the biosynthesis of normal levels of Delta-9 unsaturated fatty acids and 1-alkyl-2,3-diacylglycerol in the Harderian gland (PubMed:11500518). Required for normal production of meibum, an oily material that prevents drying of the cornea (PubMed:11533264).|||The histidine box domains are involved in binding the catalytic metal ions.|||Up-regulated by agonists that activate NR1H3 (PubMed:12815040). Up-regulated by a high-carbohydrate diet (PubMed:11441127). Up-regulated by a fat-free, high-carbohydrate diet (PubMed:12815040). Down-regulated by a high-carbohydrate diet enriched in unsaturated fatty acids (PubMed:12815040). Up-regulated by a diet containing high levels of stearate (PubMed:17127673).|||Up-regulated during the early anagen phase of the hair cycle. Thereafter, levels decrease and are very low at telogen phase. http://togogenome.org/gene/10090:Ifnl3 ^@ http://purl.uniprot.org/uniprot/Q8CGK6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the lambda interferon family.|||Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.|||Secreted http://togogenome.org/gene/10090:C2 ^@ http://purl.uniprot.org/uniprot/P21180 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||C2 is a major histocompatibility complex class-III protein.|||Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase.|||Secreted|||The MIDAS-like motif in the VWFA domain binds divalent metal cations. http://togogenome.org/gene/10090:H2bc18 ^@ http://purl.uniprot.org/uniprot/Q64525 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Cyp2b10 ^@ http://purl.uniprot.org/uniprot/Q9WUD0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Otol1 ^@ http://purl.uniprot.org/uniprot/Q4ZJM7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OTOL1 family.|||Collagen-like protein specifically expressed in the inner ear, which provides an organic scaffold for otoconia, a calcium carbonate structure in the saccule and utricle of the ear (PubMed:21655225, PubMed:24748133, PubMed:29076638). Acts as a scaffold for biomineralization: sequesters calcium and forms interconnecting fibrils between otoconia that are incorporated into the calcium crystal structure (PubMed:21655225, PubMed:24748133, PubMed:29076638). Together with OC90, modulates calcite crystal morphology and growth kinetics (PubMed:24748133).|||Expressed in the organic matrix of otoconia (at protein level) (PubMed:17300776, PubMed:22841569). Expressed in neonatal sensory epithelium of vestibular utricle and saccule and also in otoconia (PubMed:21655225).|||Homooligomer; disulfide-linked; probably forms homotrimers (PubMed:20856818, PubMed:24748133, PubMed:29076638). Interacts with OC90 (PubMed:17300776, PubMed:20856818, PubMed:21655225). Interacts with CBLN1 (PubMed:20856818).|||Not N-glycosylated.|||The C1q domain mediates calcium-binding.|||extracellular matrix http://togogenome.org/gene/10090:Vmn1r78 ^@ http://purl.uniprot.org/uniprot/K7N608 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ttll12 ^@ http://purl.uniprot.org/uniprot/Q3UDE2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the tubulin--tyrosine ligase family, the TTL domain lacks some of the ATP binding sites predicted to be essential for TTL activity (By similarity). Lacks tyrosine ligase activity in vitro (By similarity). Lacks glutamylation activity in vitro (PubMed:17499049). Although TTLL12 contains a potential SET-like domain in the N-terminus, it does not have lysine methyltransferase activity towards histone in vitro (By similarity).|||Belongs to the tubulin--tyrosine ligase family.|||Cytoplasm|||Interacts with MAVS; the interaction prevents MAVS binding to TBK1 and IKBKE. Interacts (via N-terminus) with TBK1 (via protein kinase domain). Interacts (via TTL domain) with IKBKE (via protein kinase domain). Interacts with tubulin alpha. Interacts with histone H3 and histone H4 (when trimethylated at 'Lys-20' (H4K20me3)). Interacts with CBX3.|||Midbody|||Negatively regulates post-translational modifications of tubulin, including detyrosination of the C-terminus and polyglutamylation of glutamate residues. Also, indirectly promotes histone H4 trimethylation at 'Lys-20' (H4K20me3). Probably by controlling tubulin and/or histone H4 post-translational modifications, plays a role in mitosis and in maintaining chromosome number stability. During RNA virus-mediated infection, acts as a negative regulator of the RIG-I pathway by preventing MAVS binding to TBK1 and IKBKE.|||Nucleus|||Widely expressed with highest levels in brain, kidney, liver, lung, muscle and testis.|||centrosome|||spindle http://togogenome.org/gene/10090:Hsd17b3 ^@ http://purl.uniprot.org/uniprot/P70385 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.|||Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids (PubMed:32557858). Favors the reduction of androstenedione to testosterone (PubMed:32557858). Testosterone is the key androgen driving male development and function (PubMed:32190925, PubMed:32557858). Uses NADPH while the two other EDH17B enzymes use NADH (By similarity). Androgens such as epiandrosterone, dehydroepiandrosterone, androsterone and androstanedione are accepted as substrates and reduced at C-17. Can reduce 11-ketoandrostenedione as well as 11beta-hydroxyandrostenedione at C-17 to the respective testosterone forms (By similarity). Plays a role in the rate-limiting-step for the maximum level of testosterone production by the testis but does not affect basal testosterone production (PubMed:32190925, PubMed:32557858).|||Endoplasmic reticulum|||Expressed in the testes.|||Expression is restricted to Sertoli cells in fetal life, peaks in neonatal mice, declines thereafter until the age of 21 days, and appears in Leydig cells in adulthood.|||Null males have increased circulating luteinizing hormone (LH) levels (PubMed:32557858). Null males present mild hypogonadism at adulthood represented by lowered weight of testes and several other androgen-sensitive tissues, a shortened anogenital distance, delayed puberty, and subfertility (fewer litters) (PubMed:32190925). No phenotypic alterations in the null female (PubMed:32190925, PubMed:32557858). http://togogenome.org/gene/10090:Etv3 ^@ http://purl.uniprot.org/uniprot/Q8R4Z4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ETS family.|||Nucleus|||Transcriptional repressor that contribute to growth arrest during terminal macrophage differentiation by repressing target genes involved in Ras-dependent proliferation. Represses MMP1 promoter activity. http://togogenome.org/gene/10090:Nifk ^@ http://purl.uniprot.org/uniprot/Q91VE6 ^@ PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the FHA domain of MKI67; this interaction is enhanced in mitosis.|||Chromosome|||Citrullinated by PADI4.|||Expressed in brain, heart, hind limb muscles, intestine, liver, skin and spleen.|||Phosphorylated.|||nucleolus http://togogenome.org/gene/10090:Dnajb3 ^@ http://purl.uniprot.org/uniprot/O35723 ^@ Developmental Stage|||Function|||Tissue Specificity ^@ Its expression occurs in the postmeiotic phase of male germ cell development. First detected in 30 days old mice and thereafter into adulthood. Barely detectable in 20 days old mice and absent before this period.|||May operate as a co-chaperone of the male germ cell- and haploid stage-specific Hsp70 proteins.|||Testis specific. Expression is confined to the germline without any contribution of the somatic components. http://togogenome.org/gene/10090:H2-Q1 ^@ http://purl.uniprot.org/uniprot/O19441 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Involved in the presentation of foreign antigens to the immune system.|||Membrane http://togogenome.org/gene/10090:Gm10488 ^@ http://purl.uniprot.org/uniprot/Q4KL05 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Bglap3 ^@ http://purl.uniprot.org/uniprot/P54615 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the osteocalcin/matrix Gla protein family.|||Binds strongly to apatite and calcium.|||Expressed in kidney and lung, but not in bone.|||Gamma-carboxyglutamic acid residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.|||Secreted http://togogenome.org/gene/10090:Jak2 ^@ http://purl.uniprot.org/uniprot/Q62120 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (PubMed:16824542, PubMed:17565041). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (PubMed:17024180). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (PubMed:20304997). Also phosphorylated by TEC (PubMed:9473212). Phosphorylated on tyrosine residues in response to interferon gamma signaling (By similarity). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.|||Cytoplasm|||Embryos are anemic and die around day 12.5 post-coitum (dpc). Primitive erythrocytes are found, but definitive erythropoiesis is absent. Fetal liver myeloid progenitors, although present based on the expression of lineage specific markers, fail to respond to erythropoietin (Epo), thrombopoietin (Thpo), interleukin-3 (Il3), or granulocyte and macrophage colony-stimulating factor 1 (Csf1 and Csf2). Fetal liver BFU-E and CFU-E colonies are completely absent. However, multilineage hematopoietic stem cells (CD34(low), c-kit(pos)) can be found, and B-lymphopoiesis appears intact.|||Endomembrane system|||Interacts with IL23R, SKB1 and STAM2 (By similarity). Interacts with EPOR (PubMed:8343951, PubMed:11779507). Interacts with LYN (PubMed:9573010). Interacts with SIRPA (PubMed:10842184). Interacts with SH2B1 (PubMed:17565041, PubMed:16824542). Interacts with TEC (PubMed:9473212). Interacts with IFNGR2 (via intracellular domain) (By similarity). Interacts with LEPR (Isoform B) (PubMed:11923481). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner. Interacts with STRA6 (By similarity). Interacts with ASB2; the interaction targets JAK2 for Notch-induced proteasomal degradation (By similarity).|||Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor.|||Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Nucleus|||Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1.|||Regulated by autophosphorylation, can both activate or decrease activity (PubMed:8343951, PubMed:20304997, PubMed:21726629). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (By similarity).|||Ubiquitously expressed throughout most tissues.|||Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Lypd6 ^@ http://purl.uniprot.org/uniprot/Q8BPP5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a modulator of nicotinic acetylcholine receptors (nAChRs) function in the brain (PubMed:19403274). Inhibits nicotine-induced Ca(2+) influx through nAChRs (By similarity). In vitro, specifically inhibits alpha-3:beta-4 and alpha-7 nAChR currents in an allosteric manner (By similarity). Acts as a positive regulator of Wnt/beta-catenin signaling (By similarity).|||Cell membrane|||Cytoplasm|||Detected in the frontal cortex and hippocampus (at protein level) (PubMed:25680266). Highly expressed in the brain and spinal cord, as well as dorsal root and trigeminal ganglia (PubMed:19403274).|||Interacts with nicotinic acetylcholine receptors (nAChRs) including CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2 and CHRNB4 (By similarity). Interacts (via NxI motif) with LRP6 (By similarity).|||Membrane raft|||Perikaryon|||Secreted|||The UPAR/Ly6 domain is sufficient for inhibiting alpha-3:beta-4 and alpha-7-dependent nAChR currents.|||dendrite|||synaptosome http://togogenome.org/gene/10090:Sema3b ^@ http://purl.uniprot.org/uniprot/M9MMK0|||http://purl.uniprot.org/uniprot/Q0VGP2 ^@ Caution|||Similarity ^@ Belongs to the semaphorin family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Gtf3c4 ^@ http://purl.uniprot.org/uniprot/Q8BMQ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIIC subunit 4 family.|||Essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA, tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin. Has histone acetyltransferase activity (HAT) with unique specificity for free and nucleosomal H3. May cooperate with GTF3C5 in facilitating the recruitment of TFIIIB and RNA polymerase through direct interactions with BRF1, POLR3C and POLR3F. May be localized close to the A box (By similarity).|||Nucleus|||Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with BRF1, GTF3C1, GTF3C2, GTF3C5, GTF3C6, POLR3C and POLR3F (By similarity). http://togogenome.org/gene/10090:Tuba1b ^@ http://purl.uniprot.org/uniprot/P05213 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.|||Belongs to the tubulin family.|||Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488).|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Nascent tubulin polypeptide interacts (via beta-tubulin MREC motif) with TTC5/STRAP; this interaction may result in tubulin mRNA-targeted degradation.|||Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.|||Nitration of Tyr-451 is irreversible and interferes with normal dynein intracellular distribution.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:1967194, PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREC motif mediates interaction with TTC5/STRAP and may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).|||Ubiquitously expressed with highest levels in spleen, thymus and immature brain.|||Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.|||cytoskeleton http://togogenome.org/gene/10090:Crebzf ^@ http://purl.uniprot.org/uniprot/Q91ZR3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. ATF subfamily.|||Contaminating sequence. Sequence derived from chromosome 13 in the N-terminal part.|||Interacts with HCFC1; the interaction inhibits CREB3 transcriptional activity. Interacts with CREB3; the interaction occurs only in combination with HCFC1.|||Nucleus|||Strongly activates transcription when bound to HCFC1. Suppresses the expression of HSV proteins in cells infected with the virus in a HCFC1-dependent manner. Also suppresses the HCFC1-dependent transcriptional activation by CREB3 and reduces the amount of CREB3 in the cell. Able to down-regulate expression of some cellular genes in CREBZF-expressing cells (By similarity). http://togogenome.org/gene/10090:Mta3 ^@ http://purl.uniprot.org/uniprot/Q924K8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Plays a role in maintenance of the normal epithelial architecture through the repression of SNAI1 transcription in a histone deacetylase-dependent manner, and thus the regulation of E-cadherin levels. Contributes to transcriptional repression by BCL6.|||Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with BCL6. Interacts with NACC2 (By similarity). Interacts with PWWP2B (PubMed:34180153).|||Cytoplasm|||Expressed in heart, brain, spleen, lung, liver and kidney.|||Nucleus http://togogenome.org/gene/10090:Hoxa11 ^@ http://purl.uniprot.org/uniprot/P31311 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Dpp10 ^@ http://purl.uniprot.org/uniprot/Q6NXK7 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S9B family. DPPIV subfamily.|||Cell membrane|||Detected in brain cortex (at protein level) (PubMed:22311982). Expressed in the brain, predominantly by neurons and not by glia.|||Gly-652 is present instead of the conserved Ser which is expected to be an active site residue suggesting that this protein has no peptidase activity.|||May form oligomers. Interacts with KCND1 and KCND2 (By similarity).|||N-glycosylation is important for cell surface expression, specially at Asn-258, which is crucial.|||Promotes cell surface expression of the potassium channel KCND2 (PubMed:22311982). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:22311982). Has no dipeptidyl aminopeptidase activity (Probable). http://togogenome.org/gene/10090:Gm7168 ^@ http://purl.uniprot.org/uniprot/A0AUV4 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Smok subfamily.|||Encoded on the T-complex, a region of 20-30 Mb on proximal third of mouse chromosome 17. Naturally occurring variant forms of the T-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development.|||May play a role in sperm motility, especially in the regulation of flagellar function. http://togogenome.org/gene/10090:Calhm4 ^@ http://purl.uniprot.org/uniprot/Q8CE93 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CALHM family.|||Membrane|||Pore-forming subunit of a voltage-gated ion channel. http://togogenome.org/gene/10090:Slc35f6 ^@ http://purl.uniprot.org/uniprot/Q8VE96 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SLC35F solute transporter family.|||Interacts with SLC25A5.|||Involved in the maintenance of mitochondrial membrane potential in pancreatic ductal adenocarcinoma (PDAC) cells. Promotes pancreatic ductal adenocarcinoma (PDAC) cell growth. May play a role as a nucleotide-sugar transporter (By similarity).|||Lysosome membrane|||Mitochondrion http://togogenome.org/gene/10090:Abcc8 ^@ http://purl.uniprot.org/uniprot/B2RUS7 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts with KCNJ11.|||Membrane http://togogenome.org/gene/10090:Tcl1 ^@ http://purl.uniprot.org/uniprot/H3BJP6|||http://purl.uniprot.org/uniprot/P56280|||http://purl.uniprot.org/uniprot/Q3UES7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCL1 family.|||Cytoplasm|||Endoplasmic reticulum|||Enhances the phosphorylation and activation of AKT1 and AKT2. Enhances cell proliferation, stabilizes mitochondrial membrane potential and promotes cell survival (By similarity).|||Homodimer. Interacts with AKT1, AKT2 and AKT3 (via PH domain). Interacts with PNPT1; the interaction has no effect on PNPT1 exonuclease activity (By similarity).|||Microsome|||Nucleus http://togogenome.org/gene/10090:Anapc11 ^@ http://purl.uniprot.org/uniprot/Q9CPX9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated.|||Belongs to the RING-box family.|||Cytoplasm|||Nucleus|||The RING-type zinc finger domain coordinates an additional third zinc ion.|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. Interacts with the cullin domain of ANAPC2. Interacts with UBE2D2.|||Together with the cullin protein ANAPC2, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. May recruit the E2 ubiquitin-conjugating enzymes to the complex (By similarity). http://togogenome.org/gene/10090:Phex ^@ http://purl.uniprot.org/uniprot/P70669|||http://purl.uniprot.org/uniprot/Q3TYM9 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M13 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Detected at 16 and 18 days post coitum (dpc) in vertebrae osteoblasts. Detected in calvarial tissue and in the stratum spinosum and granulosum of the overlaying epidermis at 18 dpc. Detected at postnatal day 14 in osteoblasts and osteocytes of the calvarium. Detected in tibias at postnatal day 14 in osteoblasts and a lesser degree in osteocytes, however by postnatal day 84 it is detected in osteocytes in compact bone. Detected in teeth at postnatal day 14 in odontoblasts and ameloblasts. By postnatal day 84, expression can still be detected in odontoblasts however little to no expression can be detected in ameloblasts. Detected at 18 dpc at moderate levels in macrophages within the liver, with minimal expression in brown adipose tissue. Detected at 18 dpc in suprabasal layers of the skin.|||Expressed in bone, specifically in the osteoid and in osteocytes (PubMed:11159866, PubMed:18597632). Expressed in teeth, specifically in odontoblasts and ameloblasts (PubMed:11811562). Expressed moderately by macrophages in the liver and has minimal expression in brown adipose tissue (PubMed:11811562). Also expressed in suprabasal layers of the skin (PubMed:11811562).|||Interacts with MEPE; the interaction is zinc-dependent (via ASARM motif).|||Membrane|||N-glycosylated.|||Peptidase that cleaves SIBLING (small integrin-binding ligand, N-linked glycoprotein)-derived ASARM peptides, thus regulating their biological activity (By similarity). Cleaves ASARM peptides between Ser and Glu or Asp residues (By similarity). Regulates osteogenic cell differentiation and bone mineralization through the cleavage of the MEPE-derived ASARM peptide (PubMed:11159866, PubMed:18597632, PubMed:26051469). Promotes dentin mineralization and renal phosphate reabsorption by cleaving DMP1- and MEPE-derived ASARM peptides (PubMed:26051469). Inhibits the cleavage of MEPE by CTSB/cathepsin B thus preventing MEPE degradation (By similarity). http://togogenome.org/gene/10090:Vldlr ^@ http://purl.uniprot.org/uniprot/F8WGI9|||http://purl.uniprot.org/uniprot/P98156|||http://purl.uniprot.org/uniprot/Q3UVX6|||http://purl.uniprot.org/uniprot/Q91YY0 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in heart and muscle; less in kidney, brain, ovary, testis, lung and adipose tissue. Strongly expressed in neurons (PubMed:23506116).|||Deletion mutant mice show an increase in serum triglycerides under a high fat diet, suggesting a role in extrahepatic triglyceride uptake (PubMed:11108739). In addition, these mice show a reduced high fat diet-induced inflammation and endoplasmic reticulum (ER) stress in adipose tissue in conjunction with reduced macrophage infiltration (PubMed:24293365).|||Homooligomer (By similarity). Binds to the extracellular matrix protein Reelin/RELN (PubMed:10571241). Interacts with LRP8 (By similarity). Interacts with LDLRAP1 (PubMed:12746448). Interacts with SNX17 (PubMed:12169628). Interacts with DAB1. Interacts with PCSK9 (By similarity). Interacts with PAFAH1B3 and PAFAH1B2, the catalytic complex of (PAF-AH (I)) heterotetrameric enzyme; these interactions may modulate the Reelin pathway (By similarity). Interacts with STX5; this interaction mediates VLDLR translocation from the endoplasmic reticulum to the plasma membrane (By similarity). Interacts with CLU (By similarity).|||LRP8 and VLVLR together are required for correct embryonic development in the brain. Targeted disruption of both genes results in a phenotype virtually indistinguishable from that seen in 'reeler' and 'scrambler' mice. Subtle effects of VLDLR deletion are found mainly in the cerebellum, whereas lack of LRP8 predominantly affects the positioning of the neurons in the neocortex.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism (PubMed:11108739, PubMed:24293365). Binds also to a wide range of other molecules including Reelin/RELN or apolipoprotein E/APOE-containing ligands as well as clusterin/CLU. In the off-state of the pathway LRP8 and VLDLR form homo or heterooligomers (By similarity). Upon binding to ligands, homooligomers are rearranged to higher order receptor clusters that transmit the extracellular RELN signal to intracellular signaling processes by binding to DAB1 on its cytoplasmic tail (By similarity). This interaction results in phosphorylation of DAB1 leading to the ultimate cell responses required for the correct positioning of newly generated neurons (PubMed:23506116). Later, mediates a stop signal for migrating neurons, preventing them from entering the marginal zone (PubMed:17913789).|||Ubiquitinated at Lys-839 by MYLIP leading to degradation.|||clathrin-coated pit http://togogenome.org/gene/10090:Cuta ^@ http://purl.uniprot.org/uniprot/D5MCW4|||http://purl.uniprot.org/uniprot/Q9CQ89 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the CutA family.|||Due to intron retention.|||Homotrimer. http://togogenome.org/gene/10090:ND1 ^@ http://purl.uniprot.org/uniprot/P03888|||http://purl.uniprot.org/uniprot/Q4JFN6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 1 family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or5b123 ^@ http://purl.uniprot.org/uniprot/Q8VFQ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lce1a1 ^@ http://purl.uniprot.org/uniprot/Q9CQH5 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Hcn3 ^@ http://purl.uniprot.org/uniprot/B2RRB5|||http://purl.uniprot.org/uniprot/O88705 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel HCN family.|||Cell membrane|||Detected in hypothalamus, amygdala, olfactory bulb, hippocampus and retina (at protein level). Highly expressed in brain and heart, in particular in ventricle, atrium and in sinoatrial node (SAN). Detected at low levels in skeletal muscle and lung.|||Homotetramer. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits (By similarity). Interacts with KCTD3 and PEX5L (PubMed:23382386).|||Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.|||Inhibited by Cs(1+) and ivabradine. Is apparently not activated by cAMP or cGMP.|||Membrane|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Vsig10 ^@ http://purl.uniprot.org/uniprot/D3YX43 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Vmn1r148 ^@ http://purl.uniprot.org/uniprot/Q9EPS5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or52x1 ^@ http://purl.uniprot.org/uniprot/Q8VGX3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Timp3 ^@ http://purl.uniprot.org/uniprot/P39876|||http://purl.uniprot.org/uniprot/Q54AE5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protease inhibitor I35 (TIMP) family.|||Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli.|||Highest levels are found in kidney, lung and brain followed by ovary and uterus. Low levels are found in bone.|||Highly induced by phorbol ester (PMA), EGF and transforming growth factor-beta 1. Also induced by dexamethasone.|||Interacts with EFEMP1.|||extracellular matrix http://togogenome.org/gene/10090:Lcn6 ^@ http://purl.uniprot.org/uniprot/A2AJB9|||http://purl.uniprot.org/uniprot/G8XSM1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Wls ^@ http://purl.uniprot.org/uniprot/Q6DID7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the wntless family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Detected at 6.25 dpc in the proximal epiblast at the junction between the embryonic and extraembryonic tissue. Later expression is more restricted to the primitive streak and mesoderm extending to the distal tip of the embryo. Strong expression is found in both posterior visceral endoderm and epiblast at the prestreak, but switched to the mesoderm at late-streak.|||Early endosome membrane|||Endoplasmic reticulum membrane|||Expressed in the brain, skeletal muscle, heart muscle, lung, gut, liver, and kidney (at protein level) (PubMed:20652957). In the brain, expressed in the cortex, striatum, hippocampus and to a lesser extent in the cerebellum (at protein level) (PubMed:20652957). Expressed in kidney, lung, skin, intestine, brain, spinal cord, skeleton, eyes, excretion glands, tooth and palatal shelves (PubMed:19841259). In the cerebellum, expressed in Purkinje cells (PubMed:19841259).|||Golgi apparatus membrane|||Interacts with WNT3A (By similarity). Interacts with WNT1, WNT3 and WNT5.|||Mice display embryonic lethality before 10.5 dpc. Embryos show defects in the establishment of the body axis and in the primitive streak and mesoderm formation.|||N-glycosylated.|||Regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins. Also plays an important role in establishment of the anterior-posterior body axis formation during development.|||Up-regulated by WNT1. Transcriptionally activated by beta-catenin and by LEF/TCF-dependent transcription. http://togogenome.org/gene/10090:Smad7 ^@ http://purl.uniprot.org/uniprot/B2RPW6|||http://purl.uniprot.org/uniprot/O35253 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation prevents ubiquitination and degradation mediated by SMURF1.|||Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.|||Belongs to the dwarfin/SMAD family.|||Cytoplasm|||Interacts with COPS5. Interacts with STAMBP. Interacts with PPP1R15A (By similarity). Interacts with NEDD4L. Interacts with RNF111, AXIN1 and AXIN2. Interacts with ACVR1B, SMURF1, SMURF2 and TGFBR1; SMAD7 recruits SMURF1 and SMURF2 to the TGF-beta receptor and regulates its degradation (By similarity). Interacts with WWP1. Interacts with PDPK1 (via PH domain) (By similarity). Ubiquitinated by WWP1. Interacts with TSC22D1/TSC-22; the interaction requires TGF-beta and the interaction is inhibited by TGFBR1 (By similarity).|||Nucleus|||Phosphorylation on Ser-249 does not affect its stability, nuclear localization or inhibitory function in TGFB signaling; however it affects its ability to regulate transcription (PubMed:11278814). Phosphorylated by PDPK1 (By similarity).|||Ubiquitinated by WWP1 (PubMed:15221015). Polyubiquitinated by RNF111, which is enhanced by AXIN1 and promotes proteasomal degradation (PubMed:14657019). In response to TGF-beta, ubiquitinated by SMURF1; which promotes its degradation (By similarity). Ubiquitinated by ARK2C, promoting proteasomal degradation, leading to enhance the BMP-Smad signaling (PubMed:23610558).|||Ubiquitous in various organs, with higher levels in brain and kidney. http://togogenome.org/gene/10090:Ppid ^@ http://purl.uniprot.org/uniprot/Q9CR16 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclophilin-type PPIase family. PPIase D subfamily.|||Cytoplasm|||Identified in ESR1 or NR3C1/GCR steroid receptor-chaperone complexes. Found in HSP90 chaperone complexes with kinase clients LCK or EIF2AK1. Two monomers associate with one HSP90 homodimer. Interacts with HSP90AA1. Interacts with HSP90AB1; PPID and FKBP4 compete for binding to HSP90AB1 and the interaction is mutually exclusive with the PPID:HSPA8 interaction. Interacts with HSPA8; PPID and STIP1 but not FKBP4 compete for binding to HSPA8 and the interaction is mutually exclusive with the PPID:HSP90AB1 interaction. Interacts with S100A1 and S100A2; the interactions dissociate the PPID:HSP90AA1 interaction. Interacts with S100A6. Interacts with MYB, ILF2, XRCC6, RACK1 and RPS3. Interacts with cytoplasmic dynein 1 intermediate chain (DYNC1I1 or DYNC1I2).|||Less sensitive to inhibition by cyclosporin A than is CYP-18.|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Proposed to act as a co-chaperone in HSP90 complexes such as in unligated steroid receptors heterocomplexes. Different co-chaperones seem to compete for association with HSP90 thus establishing distinct HSP90-co-chaperone-receptor complexes with the potential to exert tissue-specific receptor activity control. May have a preference for estrogen receptor complexes and is not found in glucocorticoid receptor complexes. May be involved in cytoplasmic dynein-dependent movement of the receptor from the cytoplasm to the nucleus. May regulate MYB by inhibiting its DNA-binding activity. Involved in regulation of AHR signaling by promoting the formation of the AHR:ARNT dimer; the function is independent of HSP90 but requires the chaperone activity region. Involved in regulation of UV radiation-induced apoptosis.|||This protein should not be confused with mitochondrial peptidyl-prolyl cis-trans isomerase F (PPIF) which is often referred to as cyclophilin D or CypD.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Cd53 ^@ http://purl.uniprot.org/uniprot/Q3TV80|||http://purl.uniprot.org/uniprot/Q3U0W1|||http://purl.uniprot.org/uniprot/Q61451 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell junction|||Cell membrane|||Interacts with SCIMP.|||Membrane|||Required for efficient formation of myofibers in regenerating muscle at the level of cell fusion. May be involved in growth regulation in hematopoietic cells. http://togogenome.org/gene/10090:Acot1 ^@ http://purl.uniprot.org/uniprot/O55137 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels. More active towards saturated and unsaturated long chain fatty acyl-CoAs (C12-C20).|||Expressed in heart, kidney, brown adipose tissue, white adipose tissue, adrenal gland and muscle.|||In the liver, by peroxisome proliferator (Clofibrate) treatment, via the peroxisome proliferator-activated receptors (PPARs) or fasting for 24 hours.|||Monomer.|||cytosol http://togogenome.org/gene/10090:Leap2 ^@ http://purl.uniprot.org/uniprot/Q91V13 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LEAP2 family.|||Has an antimicrobial activity.|||Secreted http://togogenome.org/gene/10090:Cst9 ^@ http://purl.uniprot.org/uniprot/Q9Z0H6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Expressed during testis cord formation in pre-Sertoli cells, at a time immediately after the peak of SRY expression.|||Expression is restricted to fetal gonads and adult testis.|||May be involved in testis development (PubMed:9826679). May play a role in hematopoietic differentiation or inflammation (By similarity). Has immunomodulatory and antimicrobial functions against Francisella tularensis, a Gram-negative bacteria (PubMed:23922243).|||No visible phenotype; probably due to redundancy with other family members.|||Secreted http://togogenome.org/gene/10090:Ccdc126 ^@ http://purl.uniprot.org/uniprot/Q8BIS8 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Lin7b ^@ http://purl.uniprot.org/uniprot/O88951 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the lin-7 family.|||Cell junction|||Cell membrane|||Expressed in the kidney; predominantly in the vasa recta.|||Forms a complex with CASK and CASKIN1 (By similarity). Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (PubMed:10846156). Forms a heterotrimeric complex composed of MMP5, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (PubMed:22337881). Forms a heterotrimeric complex with DLG1 and CASK via their L27 domains (PubMed:22337881, PubMed:15863617). Interacts with DLG4 and GRIN2B as well as CDH1 and CTNNB1, the channels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably KCNJ2/Kir2.1 and SLC6A12/BGT-1 via its PDZ domain (By similarity). The association of LIN7A with cadherin and beta-catenin is calcium-dependent, occurs at synaptic junctions and requires the actin cytoskeleton. Interacts with EGFR, ERBB2, ERBB3 and ERBB4 with both PDZ and KID domains (By similarity). Associates with KIF17 via APBA1 (By similarity). Interacts with ASIC3 (PubMed:15317815). Interacts with TOPK. Interacts with RTKN (By similarity). Interacts with APBA1 (PubMed:15863617). Interacts with MPP7 (By similarity). Interacts with DLG2 (PubMed:9753324). Interacts with DLG3 (PubMed:9753324).|||Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (PubMed:10846156). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. May increase the amplitude of ASIC3 acid-evoked currents by stabilizing the channel at the cell surface.|||Postsynaptic density membrane|||The L27 domain mediates interaction with CASK and is involved in the formation of multimeric complexes and the association of LIN7 to membranes.|||The PDZ domain regulates endocytosis and recycling of the receptor at the membrane.|||The kinase interacting site is required for proper delivery of ERBB2 to the basolateral membrane.|||tight junction http://togogenome.org/gene/10090:Hras ^@ http://purl.uniprot.org/uniprot/Q61411 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-104 prevents interaction with guanine nucleotide exchange factors (GEFs).|||Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Forms a signaling complex with RASGRP1 and DGKZ (By similarity). In its GTP-bound form interacts with PLCE1 (By similarity). Interacts with TBC1D10C and RASSF5 (By similarity). Interacts with PDE6D (By similarity). Interacts with IKZF3 (By similarity). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (By similarity). Interacts (active GTP-bound form) with RGS14 (via RBD 1 domain) (By similarity). Interacts with RACK1 (By similarity). Interacts with RAPGEF2 (By similarity). Interacts with RGL3 (PubMed:10869344). Interacts with HSPD1 (PubMed:1347942). Interacts with PIK3CG; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (PubMed:19906996). Interacts (in GTP-bound form) with Oog1 (PubMed:16580637).|||Golgi apparatus|||Golgi apparatus membrane|||Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi.|||Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.|||S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation.|||The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation.|||Ubiquitinated by the BCR(LZTR1) E3 ubiquitin ligase complex at Lys-170 in a non-degradative manner, leading to inhibit Ras signaling by decreasing Ras association with membranes. http://togogenome.org/gene/10090:Rassf1 ^@ http://purl.uniprot.org/uniprot/A9YZW8|||http://purl.uniprot.org/uniprot/Q99MK9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with ECM2 (PubMed:17335777). Interacts with RAB39B; the interaction is strong (PubMed:23294242). Does not interact with RAB39A (PubMed:23294242).|||Interacts with MAP1S and XPA (By similarity). Binds to the N-terminal of CDC20 during prometaphase (By similarity). Binds to STK3/MST2 and STK4/MST1 (By similarity). Recruited to the TNFRSF1A and TNFRSF10A complexes in response to their respective cognate ligand, after internalization (By similarity). Can self-associate (By similarity). Part of a complex with MDM2, DAXX, RASSF1 and USP7 (By similarity).|||Interacts with MOAP1 and E4F1 (By similarity). Interacts with RSSF5 and probably associates with HRAS via a RSSF1 isoform A-RSSF5 heterodimer (By similarity). Interacts (via C-terminus) with DAXX (via N-terminus); the interaction is independent of MDM2 and TP53 (By similarity). Interacts (via N-terminus) with MDM2 (via C-terminus); the interaction is independent of TP53 (By similarity). Interacts with RAB39A (PubMed:23294242). Interacts with RAB39B; the interaction is weak (PubMed:23294242).|||Nucleus|||Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage (By similarity).|||centrosome|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Ifi202b ^@ http://purl.uniprot.org/uniprot/Q9R002 ^@ Domain|||Function|||Induction|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HIN-200 family.|||By beta interferon (PubMed:2477366, PubMed:14764608). By IL6 in splenocytes (at protein level) (PubMed:14764608).|||Cytoplasm|||DNA-binding protein involved in innate immune response and has anti-inflammatory activity (PubMed:19131592, PubMed:23850291, PubMed:23567559). Inhibits caspase activation in response to cytosolic DNA by preventing activation of the AIM2 inflammasome, probably by sequestering cytoplasmic DNA and preventing its being bound by AIM2 (PubMed:19131592, PubMed:23850291, PubMed:23567559). Also inhibits activation of the AIM2 inflammasome via a direct interaction with AIM2, which prevents the interaction between AIM2 and PYCARD and formation of the AIM2 inflammasome (PubMed:23850291). Binds double-stranded DNA (dsDNA) in the cytosol (PubMed:19131592, PubMed:23850291, PubMed:23567559, PubMed:24419611). Has anti-apoptotic effects due to inhibition of the transcriptional activity of TP53/p53 (PubMed:16670293). Inhibits the transcriptional activity of several transcription factors, including NF-kappa-B p50 and p65, FOS, JUN, E2F1, E2F4, MYOD1 and myogenin (PubMed:8524315).|||Homomultimer; homotetramerizes (via HIN-200 domain 2), enhancing affinity for double-stranded DNA (dsDNA) (PubMed:9821952, PubMed:23850291). Interacts (via HIN-200 domain 2) with AIM2 (via HIN-200 domain); preventing activation of the AIM2 inflammasome (PubMed:23850291). Binds to several transcription factors, including NF-kappa-B p50 (NFKB1) and p65 (RELA), FOS, JUN, E2F1, E2F4, MYOD1 and myogenin (PubMed:8524315). Also binds TP53/p53, the hypophosphorylated, growth-inhibitory form of the retinoblastoma protein and the p53-binding protein 1 (TP53BP1) (PubMed:8910340, PubMed:16670293).|||NZB mice express 10 to 100 fold more Ifi202 in spleen than B6 or NZW mice (PubMed:11567633). This could account for the high susceptibility of NZB mice to systemic lupus (PubMed:11567633).|||Nucleus|||Phosphorylated.|||The HIN-200 domain 1 mediates non-specific double-stranded DNA (dsDNA)-binding via electrostatic interactions: it recognizes both strands of DNA (PubMed:23567559, PubMed:24419611). The HIN-200 domain 2 mediates homotetramerization and interaction with AIM2 (PubMed:23850291). http://togogenome.org/gene/10090:Phpt1 ^@ http://purl.uniprot.org/uniprot/Q9DAK9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the janus family.|||Cytoplasm|||Exhibits phosphohistidine phosphatase activity.|||Monomer. http://togogenome.org/gene/10090:Jaml ^@ http://purl.uniprot.org/uniprot/Q80UL9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily.|||Cell junction|||Cell membrane|||Expressed by gamma-delta intraepithelial T cells (at protein level).|||Homodimer; active form in leukocyte-endothelial cell adhesion. Interacts (homodimeric form) with CXADR. Interacts (via cytoplasmic domain) with the PI3 kinase; upon CXADR-binding. Interacts with ITGA4 and ITGB1; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization.|||The Ig-like V-type domain 1 mediates interaction with CXADR (PubMed:20813954). The Ig-like V-type domain 2 may also play a role in the interaction (PubMed:20813955).|||Transmembrane protein of the plasma membrane of leukocytes that control their migration and activation through interaction with CXADR, a plasma membrane receptor found on adjacent epithelial and endothelial cells. The interaction between both receptors mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. Upon epithelial CXADR-binding, JAML induces downstream cell signaling events in gamma-delta T-cells through PI3-kinase and MAP kinases. It results in proliferation and production of cytokines and growth factors by T-cells that in turn stimulate epithelial tissues repair. It also controls the transmigration of leukocytes within epithelial and endothelial tissues through adhesive interactions with epithelial and endothelial CXADR. http://togogenome.org/gene/10090:Pank3 ^@ http://purl.uniprot.org/uniprot/Q8R2W9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type II pantothenate kinase family.|||Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.|||Cytoplasm|||Highly expressed in the liver.|||Homodimer.|||Subject to allosteric regulation, exists in two distinct conformational states, a catalytically incompetent (or open) conformation stabilized by the binding of acetyl(acyl)-CoA, and a catalytically competent (or closed) conformation stabilized by ATP-binding (By similarity). Acetyl-CoA and its thioesters act as allosteric inhibitors and compete with the ATP-binding site (By similarity). Strongly inhibited by acetyl-CoA, malonyl-CoA and palmitoyl CoA and modestly inhibited by CoA (PubMed:16040613). Inhibited by calcium hopantenate (PubMed:17379144). http://togogenome.org/gene/10090:Got1l1 ^@ http://purl.uniprot.org/uniprot/Q7TSV6 ^@ Caution|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Cytoplasm|||Homodimer.|||In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.|||The residues that bind the substrate in other aspartate aminotransferases are not conserved. http://togogenome.org/gene/10090:Cpne6 ^@ http://purl.uniprot.org/uniprot/Q3UYN2|||http://purl.uniprot.org/uniprot/Q9Z140 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the copine family.|||Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Binds phospholipid membranes in a calcium-dependent manner (PubMed:9886090). Plays a role in dendrite formation by melanocytes (By similarity).|||Cell membrane|||Cytoplasm|||Endosome|||Expressed in the brain (PubMed:9645480). Expressed in pyramidal cells, granule cells, and neurons in the dentate gyrus of the hippocampus and in granule cells of the olfactory bulb (at protein level). Expressed in pyramidal cells of the CA1-CA3 regions, in granule cells of the dentate gyrus, in granule cells of the olfactory bulbs, in the mitral cell layer and in neurons of the cerebral cortex layer II, brainstem and spinal cord (PubMed:9886090). Not detected in glial cells (PubMed:9645480, PubMed:9886090).|||Interacts (via second C2 domain) with OS9 (via C-terminus); this interaction occurs in a calcium-dependent manner in vitro (PubMed:10403379). May interact with NECAB1 (By similarity).|||Perikaryon|||The C2 domain 1 binds phospholipids in a calcium-independent manner and is not necessary for calcium-mediated translocation and association to the plasma membrane (PubMed:9886090, PubMed:26175110). The C2 domain 2 binds phospholipids in a calcium-dependent manner and is necessary for calcium-mediated translocation and association to the plasma membrane (PubMed:9886090, PubMed:26175110). The linker region contributes to the calcium-dependent translocation and association to the plasma membrane (PubMed:21087455, PubMed:26175110). The VWFA domain is necessary for association with intracellular clathrin-coated vesicles in a calcium-dependent manner (PubMed:21087455).|||Up-regulated by long-term potentiation (PubMed:9645480). Up-regulated by kainate in an NMDA-type glutamate receptor-dependent manner (PubMed:9645480).|||clathrin-coated vesicle|||dendrite http://togogenome.org/gene/10090:Bambi ^@ http://purl.uniprot.org/uniprot/Q9D0L6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BAMBI family.|||Expressed at high levels during odontogenesis.|||Membrane|||Negatively regulates TGF-beta signaling. http://togogenome.org/gene/10090:Lpar5 ^@ http://purl.uniprot.org/uniprot/G3X9K0|||http://purl.uniprot.org/uniprot/Q149R9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. http://togogenome.org/gene/10090:Vdr ^@ http://purl.uniprot.org/uniprot/P48281 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||By 1,25-dihydroxyvitamin D(3) in kidney.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Homodimer in the absence of bound vitamin D3. Heterodimer with RXRA after vitamin D3 binding. Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with the corepressor NCOR1. Interacts with SNW1. Interacts with IRX4, the interaction does not affect its transactivation activity (By similarity). Interacts with CRY1 (PubMed:28751364). Interacts with CRY2 in a ligand-dependent manner (PubMed:28751364).|||Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (By similarity). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (By similarity). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (By similarity). Plays a central role in calcium homeostasis (PubMed:32354638). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638).|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Hps3 ^@ http://purl.uniprot.org/uniprot/E9PZY1|||http://purl.uniprot.org/uniprot/Q8BZ55|||http://purl.uniprot.org/uniprot/Q91VB4 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6.|||Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS5 and HPS6.|||Cytoplasm|||Defects in Hps3 are the cause of the cocoa (coa) mutant, which is characterized by hypopigmentation and platelet dysfunction (PubMed:11707070).|||Found in heart, brain, spleen, liver, lung, kidney and testis.|||Involved in early stages of melanosome biogenesis and maturation.|||cytosol http://togogenome.org/gene/10090:Plaur ^@ http://purl.uniprot.org/uniprot/P35456 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA.|||Cell membrane|||Expressed in angiogenic endothelial cells (at protein level).|||GPI-anchored form.|||Monomer (Probable). Interacts (via the UPAR/Ly6 domains) with SRPX2. Interacts with MRC2 (By similarity). Interacts with SORL1 (via N-terminal ectodomain); this interaction decreases PLAUR internalization (By similarity). The ternary complex composed of PLAUR-PLAU-SERPINE1 also interacts with SORL1 (By similarity).|||Secreted http://togogenome.org/gene/10090:Phgr1 ^@ http://purl.uniprot.org/uniprot/Q8K0G7 ^@ Sequence Caution ^@ Wrong choice of frame. http://togogenome.org/gene/10090:Cyp2c67 ^@ http://purl.uniprot.org/uniprot/Q569X9 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Hes7 ^@ http://purl.uniprot.org/uniprot/Q8BKT2 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By Notch-signaling.|||Dynamic expression in the presomitic mesoderm (PSM). At 8.5 dpc, expressed in two bilateral domains: rostral and caudal stripes. The rostral bands are located posterior to the newly formed somite, while the caudal bands extend to the most caudal tip. During 9.0 dpc-12.0 dpc stages, again specifically expressed in two domains of the PSM.|||Has a particular type of basic domain which includes a helix-interrupting proline.|||Nucleus|||The C-terminal WRPW motif is a transcriptional repression motif which is necessary for interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.|||Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.|||Transcriptional repressor. Represses transcription from both N box- and E box-containing promoters. May with HES1, cooperatively regulate somite formation in the presomitic mesoderm (PSM). May function as a segmentation clock, which is essential for coordinated somite segmentation. http://togogenome.org/gene/10090:Rps11 ^@ http://purl.uniprot.org/uniprot/P62281|||http://purl.uniprot.org/uniprot/Q3UC02 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS17 family.|||Citrullinated by PADI4.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Micu1 ^@ http://purl.uniprot.org/uniprot/Q8VCX5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MICU1 family. MICU1 subfamily.|||Expressed in skeletal muscle, heart, kidney, liver, brain, lung, fat and spleen.|||Homohexamer; in absence of calcium (By similarity). Forms a homohexamer in absence of calcium and rearranges into a heterodimer in presence of calcium (By similarity). Heterodimer; disulfide-linked; heterodimerizes with MICU2 (PubMed:23409044, PubMed:24560927). The heterodimer formed with MICU2 associates with MCU at low calcium concentration and dissociates from MCU at high calcium level (By similarity). Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (By similarity). Interacts (via polybasic region) with EMRE/SMDT1; the interaction is direct (By similarity). Interacts (via polybasic region) with MCU (via coiled coil domains); the interaction is direct and precedes formation of the heterodimer with MICU2 (PubMed:23409044). Interacts with SLC25A23 (By similarity). Interacts with CHCHD4/MIA40; which introduces the interchain disulfide bond with MICU2 (By similarity).|||Key regulator of mitochondrial calcium uniporter (MCU) that senses calcium level via its EF-hand domains (PubMed:24560927). MICU1 and MICU2 form a disulfide-linked heterodimer that stimulates and inhibits MCU activity, depending on the concentration of calcium (PubMed:24560927). MICU1 acts both as an activator or inhibitor of mitochondrial calcium uptake (By similarity). Acts as a gatekeeper of MCU at low concentration of calcium, preventing channel opening (By similarity). Enhances MCU opening at high calcium concentration, allowing a rapid response of mitochondria to calcium signals generated in the cytoplasm (PubMed:24560927). Regulates glucose-dependent insulin secretion in pancreatic beta-cells by regulating mitochondrial calcium uptake (By similarity). Induces T-helper 1-mediated autoreactivity, which is accompanied by the release of IFNG (By similarity).|||Lethality during the first hours after birth: embryos are at the expected Mendelian ratio and death takes place only after birth.|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||The C-helix is required for assembling the Ca(2+)-free homohexamer. It also plays a key role in mitochondrial calcium uptake, probably by mediating interaction with MICU2.|||The EF-hand domains have high affinity for calcium and act as sensors of calcium levels.|||The EF-hand domains have high affinity for calcium and act as sensors of mitochondrial matrix calcium levels. http://togogenome.org/gene/10090:Ssxb1 ^@ http://purl.uniprot.org/uniprot/Q9CPU1 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Pbx4 ^@ http://purl.uniprot.org/uniprot/Q99NE9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Almost exclusively expressed in testis.|||Belongs to the TALE/PBX homeobox family.|||Expressed in spermatocytes in the pachytene stage of the first meiotic prophase.|||Nucleus http://togogenome.org/gene/10090:Utrn ^@ http://purl.uniprot.org/uniprot/E9Q6R7 ^@ Subcellular Location Annotation ^@ cytoskeleton http://togogenome.org/gene/10090:Ssxb5 ^@ http://purl.uniprot.org/uniprot/Q6XAS2 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Usp19 ^@ http://purl.uniprot.org/uniprot/Q3UJD6 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates (By similarity). Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing thier ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Exhibits a preference towards 'Lys-63'-linked ubiquitin chains (By similarity). Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis.|||Endoplasmic reticulum membrane|||Interacts with and stabilizes RNF123 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A (via N-terminus) (By similarity).|||Up-regulated by ESR1 in the presence of 17 beta-estradiol (E2). http://togogenome.org/gene/10090:Arl6ip4 ^@ http://purl.uniprot.org/uniprot/Q9JM93 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ARL6IP4 family.|||Interacts with ZCCHC17 (By similarity). Interacts with SRSF2 (By similarity). Interacts with ARL6.|||Involved in modulating alternative pre-mRNA splicing with either 5' distal site activation or preferential use of 3' proximal site.|||Low quality sequence that contains many discrepancies.|||Nucleus speckle|||Widely expressed. Expressed at high level in testis and thymus.|||nucleolus http://togogenome.org/gene/10090:Kif26b ^@ http://purl.uniprot.org/uniprot/Q7TNC6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIF26 subfamily.|||Cytoplasm|||Essential for embryonic kidney development. Plays an important role in the compact adhesion between mesenchymal cells adjacent to the ureteric buds, possibly by interacting with MYH10. This could lead to the establishment of the basolateral integrity of the mesenchyme and the polarized expression of ITGA8, which maintains the GDNF expression required for further ureteric bud attraction. Although it seems to lack ATPase activity it is constitutively associated with microtubules.|||In newborn kidney, specifically expressed in the mesenchyme.|||In the developing kidney, only present in the uncommitted mesenchyme and absent from more differentiated structures including renal vesicles and comma-shaped bodies. First detected in the metanephric mesenchyme at 10.5 dpc. After 11.5 dpc, observed in mesenchymal cells surrounding the tips of ureteric buds in the metanephroi. At 11.5 dpc, also detected in limb buds and central nervous system. At 14.5 dpc, strongly expressed in the nephrogenic zone.|||Interacts with MYH10.|||Mutant mice die within 24 hours after birth. Most mice show bilateral kidney agenesis. The development of other organs seems normal. Ureteric bud attraction is impaired after 11.0 dpc. The ureteric buds are attracted close to the mesenchyme but fail to invade and branch into the mesenchyme and the kidney disappears by 14.5 dpc. The mesenchymal cells undergo apoptotic cell death at 12.5 dpc. ITGA8 is reduced at the ureteric bud/mesenchyme junction and does not exhibit basolateral localization. GDNF is not properly maintained in the mesenchyme at 11.5 dpc.|||Phosphorylation at Thr-1859 and Ser-1962 by CDKs, mainly CDK2 and CDK5, enhances the interaction with NEDD4, polyubiquitination, and subsequent proteasomal degradation. Phosphorylation occurs upon loss of interaction with microtubules.|||Polyubiquitinated by NEDD4, resulting in proteasomal degradation.|||Up-regulated by SALL1.|||cytoskeleton http://togogenome.org/gene/10090:Rasgef1c ^@ http://purl.uniprot.org/uniprot/Q9D300 ^@ Function ^@ Guanine nucleotide exchange factor (GEF). http://togogenome.org/gene/10090:Prg4 ^@ http://purl.uniprot.org/uniprot/Q9JM99 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Different forms varying in molecular weight have been observed. Such forms are possibly due to different levels of glycosylation and protein cleavage.|||First detected at the forming joint surface from 15.5 dpc, after cavitation has begun. At later stages of morphogenesis, strong expression is observed in cartilage surface cells (superficial zone chondocytes) and in the newly forming synovium.|||Highly expressed in cartilage, bone and liver and weakly expressed in heart, brain and muscle. Expressed in the surface chondrocytes and in synovial intimal cells. Isoform B is expressed in bone, small intestine, muscle, testis, heart, liver and lung. Isoform C and isoform D are widely expressed.|||Homodimer; disulfide-linked.|||Mice are viable and fertile. In the newborn period, their joints appear normal. The aged mice exhibit abnormal protein deposits on the cartilage surface and disappearance of underlying superficial zone chondrocytes. In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space become hyperplastic, which further contribute to joint failure.|||N-glycosylated.|||O-glycosylated; contains glycosaminoglycan chondroitin sulfate and keratan sulfate. O-glycosylated with sialylated oligosaccharides which are predominantly represented by the monosialylated core type I structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of disialylated O-glycans.|||Plays a role in boundary lubrication within articulating joints. Prevents protein deposition onto cartilage from synovial fluid by controlling adhesion-dependent synovial growth and inhibiting the adhesion of synovial cells to the cartilage surface.|||Proteolytically cleaved by cathepsin CTSG.|||Secreted|||The disulfide bond between Cys-795 and Cys-1053 is essential for protein cleavage. http://togogenome.org/gene/10090:Pdia2 ^@ http://purl.uniprot.org/uniprot/D3Z6P0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an intracellular estrogen-binding protein. May be involved in modulating cellular levels and biological functions of estrogens in the pancreas. May act as a chaperone that inhibits aggregation of misfolded proteins (By similarity).|||Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum lumen|||Glycosylated.|||Highly expressed in pancreas.|||Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. http://togogenome.org/gene/10090:Hspa8 ^@ http://purl.uniprot.org/uniprot/P63017 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated.|||Belongs to the heat shock protein 70 family.|||Cell membrane|||Constitutively synthesized.|||Cytoplasm|||ISGylated.|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Interacts with PACRG (By similarity). Interacts with DNAJC7 (By similarity). Interacts with DNAJB12 (via J domain) (By similarity). Interacts with DNAJB14 (via J domain) (By similarity). Interacts (via C-terminus) with the E3 ligase STUB1 forming a 210 kDa complex of one STUB1 and two HSPA8 molecules (By similarity). Interacts with CITED1 (via N-terminus); the interaction suppresses the association of CITED1 to p300/CBP and Smad-mediated transcription transactivation (By similarity). Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 (By similarity). Interacts with IRAK1BP1 and HSPH1/HSP105 (PubMed:9675148, PubMed:15292236, PubMed:17233114). Interacts with TRIM5 (By similarity). Part of a complex composed at least of ASH2L, EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, WDR5 and ZNF335; this complex may have a histone H3-specific methyltransferase activity (By similarity). Following LPS binding, may form a complex with CXCR4, GDF5 and HSP90AA1 (By similarity). Interacts with PRKN (By similarity). Interacts with FOXP3 (By similarity). Interacts with DNAJC9 (via J domain) (By similarity). Interacts with MLLT11 (By similarity). Interacts with RNF207 (By similarity). Interacts with DNAJC21 (By similarity). Interacts with DNAJB2 (By similarity). Interacts with TTC1 (via TPR repeats) (By similarity). Interacts with SGTA (via TPR repeats) (By similarity). Interacts with HSF1 (via transactivation domain) (By similarity). Interacts with HOPX, STUB1, HSP40, HSP90, BAG2 and BAG3 (By similarity). Interacts with DNAJC12 (By similarity). Interacts with HSPC138 (By similarity). Interacts with ZMYND10 (By similarity). Interacts with VGF-derived peptide TLQP-21 (By similarity). Interacts with BCL2L1, GIMAP5 and MCL1; the interaction with BCL2L1 or MCL1 is impaired in the absence of GIMAP5 (PubMed:21502331). Interacts with NLPR12 (By similarity). Interacts with TTC4 (By similarity). Interacts with TOMM70; the interaction is required for preprotein mitochondrial import (By similarity). May interact with DNJC9; the interaction seems to be histone-dependent (By similarity). Interacts with BAG5 and JPH2; the interaction with JPH2 is increased in the presence of BAG5 (By similarity).|||Lysosome membrane|||Melanosome|||Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2. KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded. Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1. Interacts with VGF-derived peptide TLQP-21.|||The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.|||Trimethylation at Lys-561 reduces fibrillar SNCA binding.|||Ubiquitous.|||nucleolus http://togogenome.org/gene/10090:Slc9a4 ^@ http://purl.uniprot.org/uniprot/Q8BUE1 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Electroneutral antiporter that exchanges sodium for protons or ammonium ions at the basolateral membrane of epithelia to regulate cell volume and intracellular pH upon hypertonic conditions (PubMed:15684419, PubMed:20484819). As part of transcellular ammonia transport in renal tubules, mediates basolateral ammonium extrusion in the medullary thick ascending limb, regulating the corticopapillary ammonium gradient and overall renal acid excretion (PubMed:20484819). Mediates sodium:proton exchange in gastric parietal cells secondary to cAMP-dependent acid secretion and hyperosmolarity. Possibly coupled to chloride:bicarbonate antiporter, enables loading of parietal cells with sodium and chloride ions to maintain cell volume and normal gastric acid secretion (PubMed:15684419). Functions as a sodium sensor in neurons of organum vasculosum of the lamina terminalis where it regulates water intake in response to increased sodium concentration in body fluids (PubMed:32372285).|||Expressed in kidney. Expressed in uterus and endometrial epithelial cells. Expressed in the inner segments of inner medullary collecting ducts (IMCD) in kidney. Expressed in AGTR1-positive neurons in organum vasculosum of the lamina terminalis (at protein level).|||Homodimer; each protomer has one site for sodium and one site for proton binding (By similarity). Interacts with CHP1 and CHP2 (By similarity).|||May be phosphorylated.|||Mice are born at the expected Mendelian rate. They display lack of renal adaptation to metabolic acidosis marked by impaired medullary ammonia accumulation and inability to increase urinary net acid excretion to recover from acidosis. They show major morphological changes in the gastric mucosa associated with decreased numbers of gastric parietal cells and hypochlorhydria.|||The number, localization and denomination of hydrophobic domains in the Na(+)/H(+) exchangers vary among authors.|||Up-regulated in response to high extracellular sodium concentration.|||Up-regulated upon metabolic acidosis.|||Zymogen granule membrane http://togogenome.org/gene/10090:Myt1l ^@ http://purl.uniprot.org/uniprot/P97500|||http://purl.uniprot.org/uniprot/Q0VGN2 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MYT1 family.|||Brain.|||Chromosome|||Expression is restricted to and present throughout the embryonic CNS and developing peripheral neural structures. In the embryonic CNS, expression is restricted to postmitotic neuronal regions. During the neurogenetic period (11 dpc-17 dpc) expression is associated temporally and spatially with the known generation of the first cortical neurons with known gradients of neuron production. Expression continues in developing postmitotic cortical neurons throughout embryonic development and is expressed within 2 days of neuronal induction in P19 cells.|||Interacts with SIN3B.|||Nucleus|||Transcription factor that plays a key role in neuronal differentiation by specifically repressing expression of non-neuronal genes during neuron differentiation (PubMed:28379941). In contrast to other transcription repressors that inhibit specific lineages, mediates repression of multiple differentiation programs (PubMed:28379941). Also represses expression of negative regulators of neurogenesis, such as members of the Notch signaling pathway, including HES1 (PubMed:28379941). The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro (PubMed:20107439, PubMed:24243019, PubMed:27281220). Directly binds the 5'-AAGTT-3' core motif present on the promoter of target genes and represses transcription by recruiting a multiprotein complex containing SIN3B (PubMed:28379941). The 5'-AAGTT-3' core motif is absent from the promoter of neural genes (PubMed:28379941).|||Up-regulated by retinoic acid. http://togogenome.org/gene/10090:Ren1 ^@ http://purl.uniprot.org/uniprot/P06281 ^@ Activity Regulation|||Function|||Induction|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase A1 family.|||In inbred mouse strains, there are at least two alleles which can occur at the Ren1 locus: Ren-1D and Ren-1C. The sequence shown is that of Ren-1C.|||Interaction with ATP6AP2 results in a 5-fold increased efficiency in angiotensinogen processing.|||Interacts with ATP6AP2.|||Kidney.|||Membrane|||Present as a single-copy gene in strains such as BALB/c and C57BL/6 while some strains such as Swiss and Akr contain two copies.|||Renal renin is synthesized by the juxtaglomerular cells of the kidney in response to decreased blood pressure and sodium concentration.|||Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.|||Secreted http://togogenome.org/gene/10090:Cd300e ^@ http://purl.uniprot.org/uniprot/Q8K249 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CD300 family.|||Cell membrane|||Interacts with TYROBP.|||Probably acts as an activating receptor. http://togogenome.org/gene/10090:Urm1 ^@ http://purl.uniprot.org/uniprot/Q9D2P4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a sulfur carrier required for 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Serves as sulfur donor in tRNA 2-thiolation reaction by being thiocarboxylated (-COSH) at its C-terminus by MOCS3. The sulfur is then transferred to tRNA to form 2-thiolation of mcm(5)S(2)U. Also acts as a ubiquitin-like protein (UBL) that is covalently conjugated via an isopeptide bond to lysine residues of target proteins such as MOCS3, ATPBD3, CTU2, USP15 and CAS. The thiocarboxylated form serves as substrate for conjugation and oxidative stress specifically induces the formation of UBL-protein conjugates.|||Belongs to the URM1 family.|||C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-adenylated (-COAMP) via the hesA/moeB/thiF part of MOCS3, then thiocarboxylated (-COSH) via the rhodanese domain of MOCS3.|||Component of a complex at least composed of URM1, CTU2/NCS2 and CTU1/ATPBD3.|||Cytoplasm http://togogenome.org/gene/10090:Or4c114 ^@ http://purl.uniprot.org/uniprot/Q7TR04 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Psmc5 ^@ http://purl.uniprot.org/uniprot/P62196 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (By similarity). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC5 and few additional components (By similarity). Component of a complex with USP49 and RUVBL1 (By similarity). Interacts with PRPF19 (PubMed:17349974). Interacts with TRIM5 (By similarity). Interacts with NDC80 (By similarity). Interacts with PAAF1 (By similarity). Interacts, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR) (PubMed:8598193). Interacts with ERCC6 (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Dbh ^@ http://purl.uniprot.org/uniprot/Q64237 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the copper type II ascorbate-dependent monooxygenase family.|||Binds 2 copper ions per subunit.|||Catalyzes the hydroxylation of dopamine to noradrenaline (also known as norepinephrine), and is thus vital for regulation of these neurotransmitters.|||Complete embryonic lethality in homozygous dams, and 88% embryonic lethality for homozygous embryos in heterozygous dams. Only 12% of the homozygous pups from heterozygous dams are alive at birth. Mutant pups have no obvious phenotype at birth, but nearly half of them die within 48 h, and only 5% survive to adulthood. Three weeks after birth, mutant pups are runted and weigh only half as much as their littermates. Still, the weight of adult males reaches 80% and that of females 88% of that of their littermates. Besides, mutant mice display ptosis. Embryonic lethality is due to a lack of noradrenaline and can be prevented by treatment with dihydroxyphenylserine, a compound that can be converted into noradrenaline in the absence of Dbh.|||Detected in adrenal gland secretory granules (at protein level) (PubMed:7961964). Detected in adrenal gland (PubMed:1280432).|||Homotetramer; composed of two disulfide-linked dimers.|||N-glycosylated.|||Proteolytic cleavage after the membrane-anchor leads to the release of the soluble form.|||chromaffin granule lumen|||chromaffin granule membrane|||secretory vesicle lumen|||secretory vesicle membrane http://togogenome.org/gene/10090:Slc38a4 ^@ http://purl.uniprot.org/uniprot/Q8R1S9 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Detected in liver, in hepatocytes surrounding the central vein (PubMed:12537539, PubMed:31570606). Not detected in heart, kidney, brain, lung, small intestine, spleen and thymus (PubMed:12537539). Highly expressed in placenta (PubMed:31570606).|||Heterozygous mice pups for SLC38A4 die shortly after birth, and only 28% of pups survive to 2 weeks. Heterozygous mice pups have a significantly reduced body and placental weight when the allele is paternally inherited while mice exhibit normal body and placental weight when the allele is inherited maternally.|||Imprinted gene expressed from the paternal allele in blastocysts.|||Symporter that cotransports neutral amino acids and sodium ions from the extraccellular to the intracellular side of the cell membrane (PubMed:12537539, PubMed:23451088, PubMed:23301202). The transport is electrogenic, pH dependent and partially tolerates substitution of Na(+) by Li(+) (PubMed:12537539). Preferentially transports smaller amino acids, such as glycine, L-alanine, L-serine, L-asparagine and L-threonine, followed by L-cysteine, L-histidine, L-proline and L-glutamine and L-methionine (By similarity).|||The disulfide bond plays an important role in substrate transport, but has no effect on trafficking to the cell surface.|||There is a disagreement about sodium-independent transport of cationic amino acids, such as L-arginine and L-lysine (By similarity). While Padmanabhan et al (PubMed:23451088) shown that SLC38A4 may mediate sodium-independent transport of cationic amino acids, such as L-arginine (PubMed:23451088). Recent studies by Fairweather et al., using quantitative LC-MS analysis, shown any transport activity of cationic amino acids, such as L-arginine and L-lysine (By similarity).|||Up-regulated by insulin.|||microvillus membrane http://togogenome.org/gene/10090:Hnrnpl ^@ http://purl.uniprot.org/uniprot/Q8R081 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Complete lethality during early embryonic development.|||Cytoplasm|||Detected in hematopoietic cells, including lymphoid progenitor cells.|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with HNRNPLL. Interacts with APEX1; the interaction is DNA-dependent. Component of a complex with SETD2 (By similarity). Interacts with ELAVL1 (By similarity). Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, ZNF827 and HNRNPK (By similarity). Interacts with CHD8 in an RNA-dependent manner.|||Phosphorylation at Ser-541 by CaMK4 enhances interaction with a CaMK4-responsive RNA element (CaRRE1), and prevents inclusion of the stress axis-regulated exon (STREX) of the KCNMA1 potassium channel transcripts upon membrane depolarization.|||RRM domain 2 has moderate RNA-binding affinity. RRM domains 3 and 4 may facilitate RNA looping when binding to two appropriately separated binding sites within the same target pre-mRNA.|||Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion (PubMed:22523384). Exhibits a binding preference for CA-rich elements. Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts. Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (By similarity). Regulates alternative splicing of a core group of genes involved in neuronal differentiation, likely by mediating H3K36me3-coupled transcription elongation and co-transcriptional RNA processing via interaction with CHD8.|||nucleoplasm http://togogenome.org/gene/10090:Supt3 ^@ http://purl.uniprot.org/uniprot/Q8BVY4 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Smarca1 ^@ http://purl.uniprot.org/uniprot/Q6PGB8 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family. ISWI subfamily.|||By ovulation in ovaries (at protein level).|||Expressed throughout the embryo at 9.5 dpc-15.5 dpc. Brain expression increases during the first two weeks of postnatal development.|||Helicase that possesses intrinsic ATP-dependent chromatin-remodeling activity (By similarity). ATPase activity is substrate-dependent, and is increased when nucleosomes are the substrate, but is also catalytically active when DNA alone is the substrate (By similarity). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (By similarity). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (By similarity). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (By similarity). The BAZ1A-, BAZ1B-, BAZ2A- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (By similarity). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (By similarity). Within the NURF-1 and CERF-1 ISWI chromatin remodeling complexes, nucleosomes are the preferred substrate for its ATPase activity (By similarity). Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development (By similarity). May promote neurite outgrowth (By similarity). May be involved in the development of luteal cells (By similarity).|||May form homodimers (By similarity). Component of the ACF-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ1A, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (By similarity). Within the complex interacts with BAZ1A; the interaction is direct (By similarity). Component of the WICH-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ1B/WSTF (By similarity). Within the complex interacts with BAZ1B/WSTF (By similarity). Component of the NoRC-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ2A/TIP5 (By similarity). Within the complex interacts with BAZ2A/TIP5 (By similarity). Component of the BRF-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and BAZ2B (By similarity). Within the complex interacts with BAZ2B (By similarity). Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1, BPTF, RBBP4 and RBBP7 (By similarity). Within the complex interacts with BPTF (By similarity). Within the complex interacts with RBBP4 and RBBP7 (By similarity). Component of the CERF-1 ISWI chromatin remodeling complex (also called the CECR2-containing-remodeling factor (CERF) complex) at least composed of CECR2 and SMARCA1 (By similarity). Within the complex interacts with CECR2 (By similarity). Component of the RSF-1 ISWI chromatin remodeling complex at least composed of SMARCA1 and RSF1 (By similarity). Within the complex interacts with RSF1 (By similarity). Interacts with PRLR (By similarity). Interacts with ERCC6 (By similarity).|||Nucleus|||Predominantly expressed in cortex, cerebellum, ovaries, testes, uterus and placenta. http://togogenome.org/gene/10090:Asb15 ^@ http://purl.uniprot.org/uniprot/Q8C565|||http://purl.uniprot.org/uniprot/Q8VHS6 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Tex19.2 ^@ http://purl.uniprot.org/uniprot/Q9D5S1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in the ectoderm and then in primordial germ cells (PGCs). Expressed in testis from embryos (13.5 dpc) to adulthood in gonocytes and spermatocytes.|||Interacts with UBR2 (PubMed:21103378). Interacts with piRNA-associated proteins DDX4, EDC4, MAEL, PIWIL1, PIWIL2, RANBP9 and TDRD6 (Probable).|||Males deficient for both for Tex19.1 and Tex19.2 have impaired spermatogenesis, small testes and are infertile. They show vacuolization and seminiferous epithelium degeneration as early as P16. They have defects in meiotic chromosome synapsis, persistence of DNA double-strand breaks during meiosis, lack of post-meiotic germ cell and up-regulation of MMERVK10C retrotransposon expression. Number of females double knockout for Tex19.1 and Tex19.2 surviving 2 weeks or more is reduced compared to males. Females display normal fertility. Surviving mutants do not present gross somatic abnormalities.|||May be required during spermatogenesis, probably by participating in the repression of retrotransposable elements and prevent their mobilization (Probable). With its paralog, Tex19.1, collaborates with the Piwi-interacting RNA (piRNA) pathway, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins. Interacts with Piwi proteins and directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:28254886).|||Specifically expressed in somatic cells of male gonad lineage. http://togogenome.org/gene/10090:Txnip ^@ http://purl.uniprot.org/uniprot/Q8BG60 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the arrestin family.|||Cytoplasm|||Homodimer; disulfide-linked. Interacts with TXN/thioredoxin through its redox-active site. Interacts with transcriptional repressors ZBTB16, ZBTB32 and HDAC1. Interacts (via C-terminus) with ITCH (via WW domains). Interacts with DDIT4 (By similarity).|||Marked reduction in the numbers of natural killer cells, low levels of Il2rb expression in the precursor hematopoietic stem cells and severe lymphoid hyperplasia in the small intestine.|||May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1) (By similarity). Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth.|||Ubiquitinated; undergoes polyubiquitination catalyzed by ITCH resulting in proteasomal degradation.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Kcna6 ^@ http://purl.uniprot.org/uniprot/Q61923 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.6/KCNA6 sub-subfamily.|||Cell membrane|||Homotetramer and heterotetramer of potassium channel proteins (Probable). Interacts with KCNAB1 and KCNAB2 (By similarity).|||The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (By similarity). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (By similarity). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (By similarity). http://togogenome.org/gene/10090:Tmcc2 ^@ http://purl.uniprot.org/uniprot/Q3T9T1|||http://purl.uniprot.org/uniprot/Q3TZY4|||http://purl.uniprot.org/uniprot/Q80W04 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TEX28 family.|||Endoplasmic reticulum membrane|||May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE.|||May form homodimers and heterodimers with TMCC2 or TMCC3 via the coiled-coil domains. Interacts with ribosomal proteins RPL4 and RPS6. Interacts with APOE and proteolytic processed C-terminal fragment C99 of the amyloid precursor protein (APP C99). http://togogenome.org/gene/10090:Gm20841 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Tysnd1 ^@ http://purl.uniprot.org/uniprot/Q9DBA6 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S1B family.|||By the proliferator-activated receptor alpha agonist bezafibrate.|||Homodimer. Forms a heterodimer with the C-terminal cleavage product (49 kDa form). Forms a heterodimer with the N-terminal cleavage product (10 kDa form). Interacts with PEX5. Interacts with LONP2.|||Inhibited by N-ethylmaleimide (NEM). Not affected by leupeptin or trans-epoxysuccinyl-l-leucylamido-(4-gianidino) butane (E64).|||Peroxisomal protease that mediates both the removal of the leader peptide from proteins containing a PTS2 target sequence and processes several PTS1-containing proteins. Catalyzes the processing of PTS1-proteins involved in the peroxisomal beta-oxidation of fatty acids (By similarity).|||Peroxisome|||Self-cleavage gives rise to an N-terminal 10-kDa fragment and C-terminal 49-kDa fragment upon import into the peroxisomes. The full-lengh TYSND1 is the active the proteolytic processing of PTS1- and PTS2-proteins and in self-cleavage, and intermolecular self-cleavage of TYSND1 down-regulates its protease activity. http://togogenome.org/gene/10090:Llgl2 ^@ http://purl.uniprot.org/uniprot/J3QJU5|||http://purl.uniprot.org/uniprot/Q3TJ91 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat L(2)GL family.|||Cytoplasm|||Interacts with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6. The complex is enhanced during mitosis. Interacts with DCAF1 (By similarity).|||Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity (By similarity).|||Phosphorylated at Ser-653 by PRKCI. Phosphorylation is enhanced during cell polarization induced by calcium. Phosphorylation may occur during the cell-cell contact-induced cell polarization and may contribute to the segregation of LLGL2 from the PRKCI/aPKC and PARD6B/Par-6 complex (By similarity). http://togogenome.org/gene/10090:Car5a ^@ http://purl.uniprot.org/uniprot/P23589 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-carbonic anhydrase family.|||Liver.|||Mitochondrial carbonic anhydrase that catalyzes the reversible conversion of carbon dioxide to bicarbonate/HCO3 (PubMed:7937950). Mitochondria are impermeable to HCO3, and thus this intramitochondrial carbonic anhydrase is pivotal in providing HCO3 for multiple mitochondrial enzymes that catalyze the formation of essential metabolites of intermediary metabolism in the urea and Krebs cycles (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Or5b101 ^@ http://purl.uniprot.org/uniprot/Q8VFX0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dnmt3a ^@ http://purl.uniprot.org/uniprot/O88508 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by binding to the regulatory factor DNMT3L (PubMed:15671018, PubMed:17713477, PubMed:21481189). Auto-methylation at Cys-706 in absence of DNA inactivates the DNA methyltransferase activity (PubMed:21481189).|||At 7.5 dpc, the protein is moderately expressed in embryonic ectoderm and weakly in mesodermal cells. At 8.5 dpc and 9.5 dpc, the expression become ubiquitous with an increase in the somites and in the ventral part of the embryo.|||Auto-methylated at Cys-706: auto-methylation takes place in absence of DNA substrate and inactivates the DNA methyltransferase activity (PubMed:21481189). Inactivation by auto-methylation may be used to inactivate unused DNA methyltransferases in the cell (PubMed:21481189).|||Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.|||Chromosome|||Cytoplasm|||Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) (By similarity). Interacts with DNMT1 and DNMT3B (By similarity). Interacts with MPHOSPH8 (By similarity). Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4) (By similarity). Binds the ZBTB18 transcriptional repressor (PubMed:11350943). Interacts with SETDB1 (By similarity). Associates with HDAC1 through its ADD domain (PubMed:11350943, PubMed:12616525). Interacts with UHRF1 (PubMed:19798101). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870). Interacts with UBC9, PIAS1 and PIAS2 (PubMed:14752048). Interacts with SPOCD1 (PubMed:32674113). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (By similarity).|||Isoform 1 is expressed ubiquitously at low levels. Expression of isoform 2 is restricted to tissues containing cells which are undergoing active de novo methylation, including spleen, testis and thymus.|||Nucleus|||Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development (PubMed:9662389, PubMed:11399089, PubMed:10555141, PubMed:11919202, PubMed:16567415, PubMed:17713477). DNA methylation is coordinated with methylation of histones (PubMed:9662389, PubMed:11399089, PubMed:10555141, PubMed:11919202, PubMed:16567415, PubMed:17713477). It modifies DNA in a non-processive manner and also methylates non-CpG sites (PubMed:9662389, PubMed:11399089, PubMed:10555141, PubMed:11919202, PubMed:16567415, PubMed:17713477). May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (PubMed:18823905). Plays a role in paternal and maternal imprinting (PubMed:15215868). Required for methylation of most imprinted loci in germ cells (PubMed:15215868). Acts as a transcriptional corepressor for ZBTB18 (PubMed:11350943). Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (PubMed:20547484). Can actively repress transcription through the recruitment of HDAC activity (PubMed:11350943). Also has weak auto-methylation activity on Cys-706 in absence of DNA (PubMed:21481189).|||Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription.|||The PWWP domain is essential for targeting to pericentric heterochromatin. It specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3) (PubMed:20547484). http://togogenome.org/gene/10090:Rpp21 ^@ http://purl.uniprot.org/uniprot/Q8R040 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic/archaeal RNase P protein component 4 family.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.|||RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA.|||nucleolus http://togogenome.org/gene/10090:Atp23 ^@ http://purl.uniprot.org/uniprot/G3UW46|||http://purl.uniprot.org/uniprot/Q9CWQ3 ^@ Similarity|||Subunit ^@ Belongs to the peptidase M76 family.|||Interacts with XRCC6. http://togogenome.org/gene/10090:Tmem212 ^@ http://purl.uniprot.org/uniprot/Q8C6V3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tmem207 ^@ http://purl.uniprot.org/uniprot/P86045 ^@ Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Interacts with WWOX.|||Intron retention.|||Membrane http://togogenome.org/gene/10090:Csmd3 ^@ http://purl.uniprot.org/uniprot/Q80T79 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CSMD family.|||Cell membrane|||Expressed in the apical dendrites of postnatal hippocampal neurons (at protein level).|||Involved in dendrite development.|||The intracellular region is dispensable for its function. http://togogenome.org/gene/10090:Tbpl2 ^@ http://purl.uniprot.org/uniprot/B7ZMZ6|||http://purl.uniprot.org/uniprot/Q6SJ95 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBP family.|||Cytoplasm|||Expressed in myotubes and myofibers (at protein level). Expressed in a wide variety of tissues with highest levels in heart, lung, liver, uterus and placenta and especially the gonads. Expression is higher in the ovary than the testis, and within the ovary expression is localized to the oocytes.|||Interacts with TAF3.|||Nucleus|||Transcription factor required in complex with TAF3 for the differentiation of myoblasts into myocytes. The complex replaces TFIID at specific promoters at an early stage in the differentiation process. http://togogenome.org/gene/10090:Svs4 ^@ http://purl.uniprot.org/uniprot/P18419 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SVP2/SVP5/SVP6 family.|||By testosterone.|||Testis.|||extracellular space http://togogenome.org/gene/10090:Tmub2 ^@ http://purl.uniprot.org/uniprot/Q3V209 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dnajc14 ^@ http://purl.uniprot.org/uniprot/Q921R4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.|||Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface. http://togogenome.org/gene/10090:Slc12a1 ^@ http://purl.uniprot.org/uniprot/P55014 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated following phosphorylation by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4).|||Apical cell membrane|||Belongs to the SLC12A transporter family.|||High affinity, high capacity cotransporter for sodium, potassium and chloride ions, with a coupling ratio 1Na(+):1K(+):2Cl(-).|||High affinity, low capacity cotransporter for sodium, potassium and chloride ions, with a coupling ratio 1Na(+):1K(+):2Cl(-).|||Inhibited by mercury dichloride and diuretic drug bumetaide. Inactive in isotonic conditions.|||Kidney-specific; most highly expressed in the cortical thick ascending limb (at protein level).|||Kidney-specific; most highly expressed in the inner stripe of outer medulla (at protein level).|||Kidney-specific; most highly expressed in the outer stripe of outer medulla (at protein level).|||Low affinity, low capacity cotransporter for sodium, potassium and chloride ions, with a coupling ratio 1Na(+):1K(+):2Cl(-).|||Phosphorylated at Ser-87, Thr-96 and Thr-101 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), promoting its activity (PubMed:21321328). Short-term cyclosporine administration increases SLC12A1 phosphorylation in kidney thick ascending limb, possibly through the inhibition of PPP3CB/calcineurin A beta phosphatase (PubMed:25967121).|||Predominantly expressed in kidney (at protein level).|||Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation. Electrically silent transporter system.|||The RFXV motif mediates binding with OXSR1/OSR1 and STK39/SPAK.|||When phosphorylated, interacts with PPP3CB. http://togogenome.org/gene/10090:Snapc4 ^@ http://purl.uniprot.org/uniprot/Q8BP86 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box (By similarity).|||Part of the SNAPc composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC4 interacts with SNAPC1, SNAPC2, SNAPC5, BRF2 and TBP (By similarity). http://togogenome.org/gene/10090:Rcn1 ^@ http://purl.uniprot.org/uniprot/Q05186 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CREC family.|||Endoplasmic reticulum lumen|||May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.|||O-glycosylated. O-mannosylated by POMT1 and POMT2 and elongated by POMGNT1.|||This protein has four functional calcium-binding sites; potential sites II and VI have lost affinity for calcium. http://togogenome.org/gene/10090:Hat1 ^@ http://purl.uniprot.org/uniprot/Q8BY71 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAT1 family.|||Catalytic subunit of the type B histone acetyltransferase (HAT) complex, composed of RBBP7 and HAT1. Interacts with histones H4 and H2A. The interaction is dependent of the ability of RBBP7 to bind to the N-terminus of histones. Component of the histone H3.1 and H3.3 complexes.|||Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair (PubMed:23754951). Coordinates histone production and acetylation via H4 promoter binding. Acetylates histone H4 at 'Lys-5' (H4K5ac) and 'Lys-12' (H4K12ac) and, to a lesser extent, histone H2A at 'Lys-5' (H2AK5ac). Drives H4 production by chromatin binding to support chromatin replication and acetylation (PubMed:23754951). Since transcription of H4 genes is tightly coupled to S-phase, plays an important role in S-phase entry and progression. Promotes homologous recombination in DNA repair by facilitating histone turnover and incorporation of acetylated H3.3 at sites of double-strand breaks (PubMed:23754951). In addition, acetylates other substrates such as chromatin-related proteins. Acetylates also RSAD2 which mediates the interaction of ubiquitin ligase UBE4A with RSAD2 leading to RSAD2 ubiquitination and subsequent degradation (By similarity).|||Homozygous deletion of HAT1 results in neonatal lethality but survival to at least late embryogenesis. The structure of the vertebrae in the neonates degenerates near the base of the spinal column.|||Mitochondrion|||Nucleus matrix|||Phosphorylated by AMPK at Ser-187; phosphorylation increases HAT1 activity. http://togogenome.org/gene/10090:Slc45a3 ^@ http://purl.uniprot.org/uniprot/Q8K0H7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycoside-pentoside-hexuronide (GPH) cation symporter transporter (TC 2.A.2) family.|||Expressed in the epididymis (PubMed:14561649). Primarily expressed in the prostate, but also in other tissues (PubMed:25164149).|||Membrane|||Proton-associated sucrose transporter. May be able to transport also glucose and fructose. http://togogenome.org/gene/10090:2700049A03Rik ^@ http://purl.uniprot.org/uniprot/E9PV87 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TALPID3 family.|||Deficient mice die during organogenesis, lack cilia, and have randomized left-right patterning, pericardial edema and hemorrhages.|||Expressed in photoreceptor cells (at protein level).|||Interacts with CEP120 (PubMed:25251415). Interacts with CCP110, CEP290, CEP97, KIF24 (By similarity).|||Photoreceptor inner segment|||Required for ciliogenesis and sonic hedgehog/SHH signaling (PubMed:21750036). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1. May play a role in early ciliogenesis in the disappearance of centriolar satellites that preceeds ciliary vesicle formation (By similarity). Involved in regulation of cell intracellular organization (PubMed:26386247). Involved in regulation of cell polarity (By similarity). Required for asymmetrical localization of CEP120 to daughter centrioles (PubMed:25251415).|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Slc25a31 ^@ http://purl.uniprot.org/uniprot/B2RTC8|||http://purl.uniprot.org/uniprot/Q3V132 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). Specifically required during spermatogenesis, probably to mediate ADP:ATP exchange in spermatocytes (PubMed:17137571, PubMed:17681941, PubMed:19556438). Large ATP supplies from mitochondria may be critical for normal progression of spermatogenesis during early stages of meiotic prophase I, including DNA double-strand break repair and chromosomal synapsis (PubMed:19556438). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31489369). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A31/ANT4 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Among nucleotides, may also exchange ADP for dATP and dADP (By similarity). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31489369). It is however unclear if SLC25A31/ANT4 constitutes a pore-forming component of mPTP or regulates it (PubMed:31489369).|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Catalyzes the exchange of ADP and ATP across the membrane.|||Expression is repressed by E2F6.|||In testis, expression increases upon transition of premeiotic type B spermatogonia into the early stages of meiosis as represented by preleptotene spermatocytes (PubMed:17681941). Continues to increase through the leptotene and zygotene spermatocyte stages, peaking in early pachytene spermatocytes (PubMed:17681941). Expression decreases in late pachytene spermatocytes and in later round spermatids (PubMed:17681941).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Male mice display a significant reduction in testicular size and are sterile, due to impaired spermatogenesis (PubMed:17681941). Males show increased levels of apoptosis within the spermatocyte layer of the seminiferous epithelium, accompanied by the absence of spermatids and spermatozoa within the seminiferous epithelium and lumen respectively (PubMed:17681941). Early meiotic arrest: an accumulation of leptotene spermatocytes, a decrease in pachytene spermatocytes and an absence of diplotene spermatocytes are observed in spermatocytes (PubMed:19556438). Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mitochondrial permeability transition pore (mPTP) (PubMed:31489369). Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca(2+)-induced mPTP formation (PubMed:31489369).|||Membrane|||Mitochondrion inner membrane|||Monomer.|||Specifically expressed in undifferentiated embryonic stem cells and germ cells (PubMed:16051982, PubMed:31489369). Expression is down-regulated after embryonic stem cells differentiation (PubMed:16051982). In adults, only expressed in developing gametes in testis (PubMed:16051982). In testis, expressed at higher level in spermatocytes. Expression is probably associated with entry of the male germ cells into meiosis (PubMed:17681941). Expressed at very low level in Sertoli cells (PubMed:17681941).|||The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).|||The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.|||flagellum membrane http://togogenome.org/gene/10090:Hbb-bh2 ^@ http://purl.uniprot.org/uniprot/B2RVB7 ^@ Caution|||Similarity ^@ Belongs to the globin family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Thbs3 ^@ http://purl.uniprot.org/uniprot/Q05895 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Can bind to fibrinogen, fibronectin, laminin and type V collagen.|||Belongs to the thrombospondin family.|||Brain, lung and cartilage.|||Oligomer; disulfide-linked. http://togogenome.org/gene/10090:Slc13a1 ^@ http://purl.uniprot.org/uniprot/Q9JHI4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.|||Expressed in the kidney.|||Highly expressed in kidney and ileum, detected at lower levels in duodenum/jejunum and colon, and at very low levels in cecum, testis, adrenal and adipose tissues.|||Sodium:sulfate symporter that mediates sulfate reabsorption in the kidney and small intestine (PubMed:10766815). Can also mediate the transport of selenate and thiosulfate (By similarity). http://togogenome.org/gene/10090:Rxylt1 ^@ http://purl.uniprot.org/uniprot/Q8VDX6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan. Participates in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity.|||Belongs to the RXYLT1 family.|||Forms a complex composed of FKTN/fukutin, FKRP and RXYLT1/TMEM5.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Inpp5b ^@ http://purl.uniprot.org/uniprot/Q8K337 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.|||Detected in kidney, liver, brain, lung and testis (at protein level). Detected in kidney and liver, and at lower levels in brain, lung and testis.|||Early endosome membrane|||Endoplasmic reticulum-Golgi intermediate compartment|||Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.|||Interacts with APPL1, PHETA1 and PHETA2. Interacts with several Rab GTPases, at least RAB1A, RAB2A, RAB5A, RAB6A, RAB8A, RAB9A and RAB33B; these interactions may play a dual role in targeting INPP5B to the specific membranes and stimulating its phosphatase activity. Interacts preferentially with non-phosphorylated RAB8A; phosphorylation of RAB8A on 'Thr-72' disrupts this interaction (By similarity). Interacts with INPP5F (PubMed:25869668).|||Isoprenylation at Cys-990 may be required for localization at the membrane.|||May be proteolytically cleaved after Lys-320 as inferred from N-terminal protein sequence of the 75 kda form.|||Membrane|||The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature, all three interactions rely on F&H motifs, an approximately 12-13 amino-acid sequence centered around Phe and His residues essential for binding (By similarity).|||cytosol|||phagosome membrane http://togogenome.org/gene/10090:Ube2d2b ^@ http://purl.uniprot.org/uniprot/Q6ZWY6 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Catalyzes the covalent attachment of ubiquitin to other proteins. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by RIG-I in response to viral infection (By similarity). Plays a role in early maturation of the testis.|||Interacts with CNOT4 (via RING domain).|||Mice show a delay in postnatal testis development but normal spermatogenesis and fertility.|||Testis-specific. http://togogenome.org/gene/10090:H1f1 ^@ http://purl.uniprot.org/uniprot/P43275 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the histone H1/H5 family.|||Chromosome|||Citrullination at Arg-56 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.|||Deficient-mice developed normally until the adult stage. No anatomic abnormalities are detected, mice are fertile and they show normal spermatogenesis and testicular morphology. The lack of phenotype may be due to a compensatory function of other histone H1 subtypes.|||H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter.|||Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Interacts with DFFB.|||Nucleus|||Restricted to thymus, testis and spleen. Present also in lymphocytic and neuronal cells. Increases in testis starting with a low level at day 5 and reaching high concentrations in 20-day old and adult animals.|||The C-terminal domain is required for high-affinity binding to chromatin. http://togogenome.org/gene/10090:Rgs10 ^@ http://purl.uniprot.org/uniprot/Q9CQE5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with GNAZ, GNAI1 and GNAI3. Associates specifically with the activated, GTP-bound forms of GNAZ and GNAI3.|||Nucleus|||Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the muscarinic acetylcholine receptor CHRM2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Modulates the activity of potassium channels that are activated in response to CHRM2 signaling. Activity on GNAZ is inhibited by palmitoylation of the G-protein.|||cytosol http://togogenome.org/gene/10090:Trak1 ^@ http://purl.uniprot.org/uniprot/Q6PD31 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A spontaneous mutation (hyrt mice) causes a recessively transmitted form of hypertonia neurological dysfunction characterized by postural abnormalities, jerky movements and tremormutant. Hyrt mice have much lower levels of GABA(A) receptors in the CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition.|||Belongs to the milton family.|||Cytoplasm|||Early endosome|||Endosome|||Interacts with RHOT1 and RHOT2. Found in a complex with KIF5B, OGT, RHOT1 and RHOT2. Interacts with HGS (By similarity). Interacts with GABRA1 (PubMed:16380713). Interacts with KIF5C. Interacts with OGT; stable interaction is not required for glycosylation of this protein by OGT. Isoform 1 interacts with OGT (By similarity).|||Involved in the regulation of endosome-to-lysosome trafficking, including endocytic trafficking of EGF-EGFR complexes and GABA-A receptors (By similarity). Involved in mitochondrial motility (PubMed:24995978). When O-glycosylated, abolishes mitochondrial motility. Crucial for recruiting OGT to the mitochondrial surface of neuronal processes (By similarity). TRAK1 and RHOT form an essential protein complex that links KIF5 to mitochondria for light chain-independent, anterograde transport of mitochondria (By similarity).|||Mitochondrion|||Mitochondrion membrane|||Nucleus|||O-glycosylated (PubMed:24995978). Glycosylated by OGT; glycosylation in response to increased extracellular glucose levels is required for and leads to regulation of mitochondrial motility by OGT (By similarity).|||Widely expressed with the greatest expression in brain, liver and kidney. Detected throughout the CNS, including the cortex, hippocamps, thalamus and various subcortical nuclei of the forebrain and midbrain, the granule of Purkinje layers of the cerebellum and the gray matter of the spinal cord. High level detected in lower moter neurons (at protein level).|||cell cortex http://togogenome.org/gene/10090:Gramd1a ^@ http://purl.uniprot.org/uniprot/Q8VEF1 ^@ Domain|||Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (PubMed:30220461). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (PubMed:30220461). Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol (PubMed:30220461). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (PubMed:30220461). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (PubMed:30220461). May play a role in tumor progression (PubMed:27585821). Plays a role in autophagy regulation and is required for biogenesis of the autophagosome. This function in autophagy requires its cholesterol-transfer activity (By similarity).|||Endoplasmic reticulum membrane|||GRAM domain binds phosphatidylserine in the PM and mediates protein recruitment to endoplasmic reticulum-plasma membrane contact sites (EPCS) in response to excess cholesterol in the PM.|||Highly expressed in the brain.|||Intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||VASt (VAD1 Analog of StAR-related lipid transfer) domain, also known as ASTER (Greek for star) domain is a sterol-binding domain.|||autophagosome http://togogenome.org/gene/10090:Vmn1r68 ^@ http://purl.uniprot.org/uniprot/E9Q0V3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cenpm ^@ http://purl.uniprot.org/uniprot/Q9CQA0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres (By similarity).|||Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS (By similarity).|||Cytoplasm|||Nucleus|||kinetochore http://togogenome.org/gene/10090:Fcer1g ^@ http://purl.uniprot.org/uniprot/P20491 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein containing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. As a component of the high-affinity immunoglobulin E (IgE) receptor, mediates allergic inflammatory signaling in mast cells (PubMed:14764707). As a constitutive component of interleukin-3 receptor complex, selectively mediates interleukin 4/IL4 production by basophils, priming T-cells toward effector T-helper 2 subset (PubMed:19098920). Associates with pattern recognition receptors CLEC4D and CLEC4E to form a functional signaling complex in myeloid cells. Binding of mycobacterial trehalose 6,6'-dimycolate (TDM) to this receptor complex leads to phosphorylation of ITAM, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes (PubMed:23602766) (Probable). May function cooperatively with other activating receptors. Functionally linked to integrin beta-2/ITGB2-mediated neutrophil activation (PubMed:17086186). Also involved in integrin alpha-2/ITGA2-mediated platelet activation (PubMed:9171347).|||Belongs to the CD3Z/FCER1G family.|||Cell membrane|||Expressed in mast cells (at protein level) (PubMed:14764707). Expressed in basophils (at protein level) (PubMed:19098920).|||IgE Fc receptor is a tetramer of an alpha chain, a beta chain, and two disulfide linked gamma chains. Associates with FCGR1A; forms a functional signaling complex (By similarity). The signaling subunit of immunoglobulin gamma (IgG) Fc receptor complex. As a homodimer or a heterodimer of CD247 and FCER1G, associates with the ligand binding subunit FCGR3A to form a functional receptor complex (By similarity). Associates with CLEC6A (PubMed:17050534). Interacts with CLEC4E (PubMed:23602766, PubMed:18776906). Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK, enabling integrin-mediated activation of neutrophils and macrophages (PubMed:17086186). Interacts with CSF2RB and recruits SYK in response to IL3 stimulation; this interaction is direct (PubMed:19098920). Interacts with CD300LH; the interaction may be indirect (PubMed:20817736). Interacts with CD300LD (PubMed:20817736). Interacts with TARM1 (By similarity).|||Knockout mice are resistant to IgE-mediated systemic anaphylaxis. http://togogenome.org/gene/10090:Foxred1 ^@ http://purl.uniprot.org/uniprot/Q3TQB2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with components of the mitochondrial respiratory chain complex I.|||Mitochondrion inner membrane|||Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I). Involved in mid-late stages of complex I assembly. http://togogenome.org/gene/10090:Ly6e ^@ http://purl.uniprot.org/uniprot/Q64253 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By interferon gamma/IFN-gamma on resting T-cells.|||Cell membrane|||GPI-anchored cell surface protein that regulates T-lymphocytes proliferation, differentiation, and activation (PubMed:9575182, PubMed:8642345). Regulates the T-cell receptor (TCR) signaling by interacting with component CD3Z/CD247 at the plasma membrane, leading to CD3Z/CD247 phosphorylation modulation (PubMed:9575182). Restricts the entry of murine coronavirus, mouse hepatitis virus, by interfering with spike protein-mediated membrane fusion (PubMed:32704094). Also plays an essential role in placenta formation by acting as the main receptor for syncytin-A (SynA) (PubMed:28679758). Therefore, participates in the normal fusion of syncytiotrophoblast layer I (SynT-I) and in the proper morphogenesis of both fetal and maternal vasculatures within the placenta (PubMed:29500366). May also act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-3:beta-4-containing nAChRs maximum response (PubMed:26276394).|||Interacts with CHRNA4 (PubMed:26276394). Interacts with CD3Z/CD247 (PubMed:9575182).|||Knockout mice show embryonic lethality at 14.5 dpc (PubMed:11784869). Lethality is due to a critical role in the trophoblast stem cells which form the outer layer of fetal part of the placenta. Alters syncytiotropoblast-I layer I (SynT-I) fusion while SynT-II cell fusion does not seem to be affected, indicating a cell autonomous role in SynT-I fusion (PubMed:29500366). Konckout mice specific to immune cells are highly susceptible to the murine coronavirus, mouse hepatitis virus (PubMed:32704094).|||Ubiquitously expressed in mouse adult tissues with maximal expression in the lung and the salivary gland. Expression is strikingly lower in the fetal tissues except for the placenta (PubMed:28679758). Present in thymus where its expression is observed in immature thymocytes and thymic stromal cells (PubMed:1531995). Also found on functionally active T-cells as well as B-cells and thymic dendritic cells (PubMed:2987354). http://togogenome.org/gene/10090:Kcnd1 ^@ http://purl.uniprot.org/uniprot/A2AEX0|||http://purl.uniprot.org/uniprot/Q03719 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.1/KCND1 sub-subfamily.|||Homotetramer or heterotetramer with KCND2 and/or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DPP10 (By similarity).|||Membrane|||Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in the heart and I(Sa) current in neurons. Channel properties are modulated by subunit assembly.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||dendrite http://togogenome.org/gene/10090:Spink2 ^@ http://purl.uniprot.org/uniprot/Q8BMY7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ As a strong inhibitor of acrosin, it is required for normal spermiogenesis. It probably hinders premature activation of proacrosin and other proteases, thus preventing the cascade of events leading to spermiogenesis defects (PubMed:21705336, PubMed:28554943). May be involved in the regulation of serine protease-dependent germ cell apoptosis (PubMed:21705336). It also inhibits trypsin (PubMed:21705336).|||Expressed in sperm (at protein level). Expressed in testis but not in ovary, brain, heart, kidney or lung. Within testis, expressed in epididymis and germ cells.|||First expressed at 16 days postpartum (dpp). Level increases until 20 dpp and is maintained into adulthood (at protein level).|||Knockout male mice are completely infertile, whereas no reproductive defects are observed in females. Spermatozoa are completely absent from caudal epididymis, which only contains round cells likely corresponding to round spermatids and multinucleated cells. Seminiferous tubules contain germ cells up to the early round-spermatid stage but condensed and elongated spermatids and mature spermatozoa are completely absent. Round spermatids do not contain an acrosomal vesicle.|||On the 2D-gel the determined pI of this protein is: 5, its MW is: 8 kDa.|||Secreted|||acrosome http://togogenome.org/gene/10090:Stag1 ^@ http://purl.uniprot.org/uniprot/F8WHU7|||http://purl.uniprot.org/uniprot/Q9D3E6 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCC3 family.|||Chromosome|||Cohesin complexes are composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein (STAG1, STAG2 or STAG3). In cohesin complexes, STAG1 is mutually exclusive with STAG2 and STAG3. Interacts directly with RAD21 in cohesin complex. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (By similarity).|||Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate.|||Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis (By similarity).|||Nucleus|||Part of the cohesin complex which is composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein.|||Phosphorylated by PLK1. The large dissociation of cohesin from chromosome arms during prophase is partly due to its phosphorylation (By similarity).|||Probable exon deletions within the cDNA.|||centromere http://togogenome.org/gene/10090:Or6c5c ^@ http://purl.uniprot.org/uniprot/Q7TRI1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pou2af1 ^@ http://purl.uniprot.org/uniprot/Q64693 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ B-cell specific.|||Belongs to the POU2AF family.|||In B cells, expression is highly increased upon activation by LPS or CpG.|||In the N-terminus possesses a conserved domain OCA for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif.|||Interacts with POU2F1/OCT1 and POU2F2/OCT2; the interaction increases POU2F1 and POU2F2 transactivation activity.|||Mutants show severely reduced or absent germinal center B cells in the lung-draining lymphatic nodes when infected by influenza virus.|||Nucleus|||Transcriptional coactivator that specifically associates with either POU2F1/OCT1 or POU2F2/OCT2. It boosts the POU2F1/OCT1 mediated promoter activity and to a lesser extent, that of POU2F2/OCT2. It recognizes the POU domains of POU2F1/OCT1 and POU2F2/OCT2. It is essential for the response of B-cells to antigens and required for the formation of germinal centers (PubMed:23045607). Regulates IL6 expression in B cells as POU2F2/OCT2 coactivator (PubMed:23045607).|||Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Mns1 ^@ http://purl.uniprot.org/uniprot/Q61884 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Able to form oligomers (PubMed:22396656). Interacts with ODAD1 (By similarity).|||Belongs to the MNS1 family.|||Expressed in the ventral embryonic node at developmental stage 8 dpc.|||High expression in testis (PubMed:22396656). Expressed in pachytene spermatocytes and post-meiotic spermatids (PubMed:8032679, PubMed:22396656).|||MNS1-deficient mice display situs inversus and hydrocephalus. They are sterile, exhibit a sharp reduction in sperm production, and remnant spermatozoa are immotile with abnormal short tails.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). May play a role in the control of meiotic division and germ cell differentiation through regulation of pairing and recombination during meiosis. Required for sperm flagella assembly (PubMed:22396656). May play a role in the assembly and function of the outer dynein arm-docking complex (ODA-DC). ODA-DC mediates outer dynein arms (ODA) binding onto the axonemal doublet microtubules (By similarity).|||Nucleus|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Vmn1r219 ^@ http://purl.uniprot.org/uniprot/Q8R271 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Frrs1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFP4|||http://purl.uniprot.org/uniprot/Q8K385 ^@ Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FRRS1 family.|||Binds 2 heme b groups non-covalently.|||Down-regulated in kidney and liver of mice lacking hypotransferrinemic (hpx), which have iron overload of the liver and pancreas.|||Expressed in spleen, liver and kidney with low expression in brain. Localizes in adult brain to the choroid plexus of the fourth, third, and lateral ventricles and to ependymal cells that line the ventricles.|||Ferric-chelate reductases reduce Fe(3+) to Fe(2+) before its transport from the endosome to the cytoplasm.|||Membrane http://togogenome.org/gene/10090:Samd7 ^@ http://purl.uniprot.org/uniprot/Q8C8Y5 ^@ Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in the retina and the pineal gland. In the retina, it is predominantly expressed in the outer nuclear layer.|||Involved in the regulation of gene expression in the retina. It functions as a negative regulator of CRX-controlled genes.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Transcriptionally regulated by CRX. http://togogenome.org/gene/10090:Msx3 ^@ http://purl.uniprot.org/uniprot/B2RPS3|||http://purl.uniprot.org/uniprot/P70354 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a potent transcriptional repressor of MSX1.|||Belongs to the Msh homeobox family.|||Nucleus|||Part of a complex composed of MSX3, CREBBP/CBP AND EP300/p300; the interaction with MSX3 decreases histone acetylation activity (PubMed:11115394). Interacts with HDAC1 (PubMed:11115394). Interacts with CREBBP/CBP, TBP and SP1 (PubMed:10215616).|||Restricted to the dorsal embryonic central nervous system. http://togogenome.org/gene/10090:C1s1 ^@ http://purl.uniprot.org/uniprot/E9Q6C2|||http://purl.uniprot.org/uniprot/Q14DT6|||http://purl.uniprot.org/uniprot/Q8CG14 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain.|||C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4 (By similarity).|||Inhibited by SERPING1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Predominantly expressed in liver.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Or4l1 ^@ http://purl.uniprot.org/uniprot/E9PZU2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Foxn2 ^@ http://purl.uniprot.org/uniprot/E9Q7L6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Flna ^@ http://purl.uniprot.org/uniprot/B7FAU9 ^@ Similarity ^@ Belongs to the filamin family. http://togogenome.org/gene/10090:Serpina1f ^@ http://purl.uniprot.org/uniprot/E9PUC6|||http://purl.uniprot.org/uniprot/G3X9Z5|||http://purl.uniprot.org/uniprot/Q9DCQ7 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Expressed predominantly in epididymis where it is found in the epithelial cells of the caput, corpus and cauda epididymis.|||Expression decreases following castration. Administration of testosterone restores expression levels.|||Expression increases gradually from post-natal day 1 to week 2, increases significantly from week 2 to week 4 and remains high thereafter.|||Inhibitor of serine proteases.|||Murine alpha-1-antitrypsin is represented by a cluster of up to 6 individual Serpina1-related genes. The precise complement of Serpina1-related genes present varies according to the strain of the animal.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable. Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity (By similarity). http://togogenome.org/gene/10090:Col12a1 ^@ http://purl.uniprot.org/uniprot/Q60847 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals have fragile bones with a disorganized collagen fiber arrangement, decreased expression of bone matrix proteins, and decreased bone-forming activity associated with delayed terminal differentiation. They have also decreased grip strength, a delay in fiber-type transition, and a deficiency in passive force generation, while the muscle seemed more resistant to eccentric contraction-induced force drop, indicating a role for a matrix-based passive force-transducing elastic element in the generation of the weakness.|||Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.|||Highest expression in tendons, perichondrium, skin, cornea, sclera, blood vessels, and periosteum.|||Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.|||O-glycosylation of isoform 2; glycosaminoglycan of chondroitin-sulfate type.|||The long NC3 XIIA isoforms are predominant at early stages (ED7 and 11); at later stages of development (ED15 and 17) the short NC3 XIIB forms become the major forms. As the short NC3 forms become the major product, the long splice variant continues to be expressed in several tissues, even after birth. The long NC1 isoforms, XIIA-1 and XIIB-1, peak in 15-day old embryos and decrease in 17-day old ones. The expression of the short NC1 form XIIB-2 remains constant throughout late stages of embryonic development (ED15 and ED17).|||The triple-helical tail is stabilized by disulfide bonds at each end.|||Trimer of identical chains each containing 190 kDa of non-triple-helical sequences.|||Type XII collagen interacts with type I collagen-containing fibrils, the COL1 domain could be associated with the surface of the fibrils, and the COL2 and NC3 domains may be localized in the perifibrillar matrix.|||extracellular matrix http://togogenome.org/gene/10090:Pnliprp2 ^@ http://purl.uniprot.org/uniprot/P17892 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||CLPS stimulates triacylglycerol lipase activity (PubMed:21382969, PubMed:2302735). Triacylglycerol lipase activity is not inhibited by increasing bile salt concentration (PubMed:21382969).|||Expressed in acinar cells of pancreas (at protein level).|||It is uncertain whether Met-1 or Met-15 is the initiator.|||Lipase that primarily hydrolyzes triglycerides and galactosylglycerides (PubMed:21382969, PubMed:9813028). In neonates, may play a major role in pancreatic digestion of dietary fats such as milk fat globules enriched in long-chain triglycerides (PubMed:9813028). Hydrolyzes short-, medium- and long-chain fatty acyls in triglycerides without apparent positional specificity (PubMed:21382969). Can completely deacylate triacylglycerols (By similarity). When the liver matures and bile salt synthesis increases, likely functions mainly as a galactolipase and monoacylglycerol lipase. Hydrolyzes monogalactosyldiglycerols (MGDG) and digalactosyldiacylglycerols (DGDG) present in a plant-based diet, releasing long-chain polyunsaturated fatty acids (By similarity). Hydrolyzes medium- and long-chain fatty acyls in galactolipids (By similarity). May act together with LIPF to hydrolyze partially digested triglycerides (By similarity). Hydrolyzes long-chain monoglycerides with high efficiency (By similarity). In cytotoxic T cells, contributes to perforin-dependent cell lysis, but is unlikely to mediate direct cytotoxicity (PubMed:2302735, PubMed:9813028, PubMed:19451396). Also has low phospholipase activity (By similarity). In neurons, required for the localization of the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) to neurite tips through acyl chain remodeling of membrane phospholipids (By similarity). The resulting OPPC-rich lipid membrane domain recruits the t-SNARE protein STX4 by selectively interacting with the STX4 transmembrane domain and this promotes surface expression of the dopamine transporter SLC6A3/DAT at neurite tips by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity).|||Secreted|||Suckling mutant mice show inefficient fat digestion associated with fat malabsorption and decreased rates of weight gain.|||Up-regulated in CD8-positive T cells by IL4/interleukin-4.|||Zymogen granule membrane|||neuron projection http://togogenome.org/gene/10090:Nucks1 ^@ http://purl.uniprot.org/uniprot/Q80XU3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromatin-associated protein involved in DNA repair by promoting homologous recombination (HR). Binds double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures, but with less affinity than RAD51AP1.|||Chromosome|||Does not interact with RAD51.|||Nucleus|||Phosphorylated in an ATM-dependent manner in response to DNA damage. Phosphorylated by CDK1 and casein kinase. http://togogenome.org/gene/10090:Sh3glb2 ^@ http://purl.uniprot.org/uniprot/Q8R3V5 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the endophilin family.|||Cytoplasm|||Homodimer, and heterodimer with SH3GLB1.|||Intron retention. http://togogenome.org/gene/10090:Sstr2 ^@ http://purl.uniprot.org/uniprot/P30875 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cerebrum and kidney.|||Cytoplasm|||Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain) (By similarity).|||Phosphorylated on serine and threonine residues in response to agonist stimulation, leading to receptor desensitization and rapid internalization. Phosphorylated to a greater extent on serine than threonine residues. Threonine phosphorylation is required for arrestin binding and receptor endocytosis but is not necessary for desensitization (By similarity).|||Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization. http://togogenome.org/gene/10090:Hpgds ^@ http://purl.uniprot.org/uniprot/Q9JHF7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Sigma family.|||Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity.|||Cytoplasm|||Expressed in skin and oviduct.|||Glutathione is required for the prostaglandin D synthase activity.|||Homodimer. http://togogenome.org/gene/10090:Pramel26 ^@ http://purl.uniprot.org/uniprot/Q66JS9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Neu4 ^@ http://purl.uniprot.org/uniprot/C5NTX9|||http://purl.uniprot.org/uniprot/Q8BZL1 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 33 family.|||Cell membrane|||Down-regulated upon neuron differentiation.|||Endoplasmic reticulum membrane|||Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides. Efficiently hydrolyzes gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3 (PubMed:19506080, PubMed:22393058). Hydrolyzes poly-alpha-(2->8)-sialylated neural cell adhesion molecule NCAM1 likely at growth cones, suppressing neurite outgrowth in hippocampal neurons (PubMed:19506080, PubMed:22393058). May desialylate sialyl Lewis A and X antigens at the cell surface, down-regulating these glycan epitopes recognized by SELE/E selectin in the initiation of cell adhesion and extravasation (By similarity). Has sialidase activity toward mucin, fetuin and sialyllactose (PubMed:19506080, PubMed:22393058).|||Expressed at low levels in embryonic brain, then rapidly up-regulated after birth reaching a maximum at postnatal day 14, followed by a decrease.|||Highly expressed in brain, particularly in hippocampus, and at lower levels in liver and spleen. Expressed in hippocampal neurons (at protein level).|||Lysosome lumen|||Microsome membrane|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||neuron projection http://togogenome.org/gene/10090:Ddx27 ^@ http://purl.uniprot.org/uniprot/Q921N6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with PeBoW complex, composed of BOP1, PES1 and WDR12. Interacts directly with BOP1 and PES1.|||Belongs to the DEAD box helicase family. DDX27/DRS1 subfamily.|||Chromosome|||Probable ATP-dependent RNA helicase. Component of the nucleolar ribosomal RNA (rRNA) processing machinery that regulates 3' end formation of ribosomal 47S rRNA.|||The C-terminal domain regulates nucleolar localization.|||nucleolus http://togogenome.org/gene/10090:Fyb ^@ http://purl.uniprot.org/uniprot/O35601 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells (PubMed:9207119, PubMed:10497204). May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton (By similarity). Modulates the expression of IL2 (PubMed:9207119, PubMed:10497204). Involved in platelet activation (PubMed:17003372). Prevents the degradation of SKAP1 and SKAP2 (By similarity). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (PubMed:12681493).|||Cell junction|||Cytoplasm|||Expressed in hematopoietic tissues such as myeloid and T-cells, spleen and thymus. Not expressed in B-cells, nor in non-lymphoid tissues. FYB-130 is preferentially expressed in mature T-cells compared to FYB-120, whereas thymocytes showed a greater relative amount of FYB-120. Expressed in podocytes.|||Nucleus|||Part of a complex consisting of SKAP2, FYB1 and PTPNS1 (PubMed:10469599). Part of a complex consisting of SKAP2, FYB1 and LILRB3 (PubMed:10469599). Part of a complex consisting of SKAP1, FYB1 and CLNK (PubMed:12681493). Interacts with CLNK (via its SH2 domain); this interaction allows SKAP1 and FYB1 to recruit FYN to the complex, thus promoting the phosphorylation of CLNK by FYN (PubMed:12681493, PubMed:10497204, PubMed:9207119). Interacts with FYN (PubMed:9207119, PubMed:10497204). Interacts with LCP2 (PubMed:9207119, PubMed:10497204). Interacts with SKAP1 (PubMed:12681493). Interacts with SKAP2 (PubMed:10469599, PubMed:11207596, PubMed:17003372). Interacts with FASLG (By similarity). Interacts with EVL (By similarity). Interacts with TMEM47 (PubMed:21881001). Interacts with LCK (By similarity).|||Slight defects in platelet function.|||T-cell receptor ligation leads to increased tyrosine phosphorylation. http://togogenome.org/gene/10090:Rab1a ^@ http://purl.uniprot.org/uniprot/P62821 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Early endosome|||Endoplasmic reticulum|||Golgi apparatus|||May interact with YIPF5 (By similarity). Interacts with C9orf72; the interaction mediates recruitment of RAB1A to the ATG1/ULK1 kinase complex (PubMed:24549040). Interacts with GDI1; this promotes dissociation from membranes (By similarity).|||Melanosome|||Membrane|||Phosphorylated by CDK1 kinase during mitosis.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:20639577, PubMed:22854043). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:20639577, PubMed:22854043). RAB1A regulates vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment and on to the cell surface, and plays a role in IL-8 and growth hormone secretion (By similarity). Required to modulate the compacted morphology of the Golgi. Regulates the level of CASR present at the cell membrane (By similarity). Plays a role in cell adhesion and cell migration, via its role in protein trafficking (PubMed:20639577). Plays a role in autophagosome assembly and cellular defense reactions against pathogenic bacteria (By similarity). Plays a role in microtubule-dependent protein transport by early endosomes and in anterograde melanosome transport (PubMed:22854043).|||cytosol http://togogenome.org/gene/10090:Csl ^@ http://purl.uniprot.org/uniprot/Q80X68|||http://purl.uniprot.org/uniprot/Q9DAM4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the citrate synthase family.|||Homodimer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Gfm1 ^@ http://purl.uniprot.org/uniprot/Q8K0D5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.|||Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.|||Mitochondrion http://togogenome.org/gene/10090:Acss1 ^@ http://purl.uniprot.org/uniprot/Q3UJ89|||http://purl.uniprot.org/uniprot/Q69Z91|||http://purl.uniprot.org/uniprot/Q99NB1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||By fasting.|||Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:11150295, PubMed:16790548). Acetate is the preferred substrate (PubMed:11150295, PubMed:16790548). Can also utilize propionate with a much lower affinity (PubMed:11150295). Provides acetyl-CoA that is utilized mainly for oxidation under ketogenic conditions (PubMed:11150295). Involved in thermogenesis under ketogenic conditions, using acetate as a vital fuel when carbohydrate availability is insufficient (PubMed:19187775).|||Highly expressed in heart, testis, kidney, skeletal muscle, lung and spleen. Detected at low levels in brain.|||Inhibited by acetylation at Lys-635 and activated by deacetylation mediated by the deacetylase SIRT3.|||Interacts with SIRT3.|||Mitochondrion matrix|||No visible phenotype at birth, but exhibit significant growth retardation at the time of weaning. Attain normal size and weight when fed normally. Exhibit hypothermia and hypoglycemia when fed high-fat, low-carbohydrate diet, leading to 50% mortality. Display strongly reduced whole-body acetate oxidation when fasting. Fasting adults exhibit hypothermia, reduced capacity to sustain running and low ATP levels.|||Reversibly acetylated at Lys-635 (PubMed:16790548). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylase SIRT3. http://togogenome.org/gene/10090:Cela3b ^@ http://purl.uniprot.org/uniprot/Q9CQ52 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Elastase subfamily.|||Efficient protease with alanine specificity but only little elastolytic activity. http://togogenome.org/gene/10090:Ifnab ^@ http://purl.uniprot.org/uniprot/L7MTU6|||http://purl.uniprot.org/uniprot/Q61719 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Oard1 ^@ http://purl.uniprot.org/uniprot/Q8R5F3 ^@ Activity Regulation|||Function|||Subcellular Location Annotation ^@ ADP-ribose glycohydrolase that hydrolyzes ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on glutamate and O-acetyl-ADP-D-ribose. Specifically acts as a glutamate mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to glutamate residues on proteins. Does not act on poly-ADP-ribosylated proteins: the poly-ADP-ribose chain of poly-ADP-ribosylated glutamate residues must by hydrolyzed into mono-ADP-ribosylated glutamate by PARG to become a substrate for OARD1. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively.|||Chromosome|||Subject to competitive inhibition by the product ADP-ribose.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:E2f5 ^@ http://purl.uniprot.org/uniprot/Q61502 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E2F/DP family.|||Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with DP-1 to E2F sites. Interaction with retinoblastoma protein RB1 or proteins RBL1 and RBL2 inhibits the E2F transactivation domain. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity).|||In the developing epidermis, first detected in 13.5-14.5 dpc embryos. With the appearance of stratified epithelium, levels of E2F5 expression increase and by 16.5 dpc, high expression found in the suprabasal cell layers. High expression also found in other regions with stratified squamous epithelia including the developing palate, lip and tongue. In the developing nervous system, first detected in the forebrain at 9.5 dpc. At 10.5 dpc, strongly expressed in the rostral region of the spinal cord. By 11.5 dpc, E2F5 is expressed throughout the developing central nervous system. In 12.5-15.5 dpc embryos, expression found in the undifferentiated ventricular regions of the brain. In the retina, expressed, in 14.5-18.5 dpc embryos, in the retinoblastic cell layer. In other developing tissues, highly expressed in the choroid plexus. Also found in the kidney, liver, lung, heart and weakly, in developing skeletal muscle and chondrocytes.|||Nucleus|||Transcriptional activator that binds to E2F sites, these sites are present in the promoter of many genes whose products are involved in cell proliferation. May mediate growth factor-initiated signal transduction. It is likely involved in the early responses of resting cells to growth factor stimulation. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis. http://togogenome.org/gene/10090:Ndufc2 ^@ http://purl.uniprot.org/uniprot/Q9CQ54 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis but required for the complex assembly. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFC2 subunit family.|||Complex I is composed of 45 different subunits. Interacts with TMEM242 (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ift70a1 ^@ http://purl.uniprot.org/uniprot/Q99J38 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TTC30/dfy-1/fleer family.|||Interacts wit the IFT B complex component IFT52.|||Required for polyglutamylation of axonemal tubulin. Plays a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip.|||cilium http://togogenome.org/gene/10090:Vmn1r125 ^@ http://purl.uniprot.org/uniprot/L7N227 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Klrd1 ^@ http://purl.uniprot.org/uniprot/O54707 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Can form disulfide-bonded heterodimer with NKG2 family members KLRC1 and KLRC2. KLRD1-KLRC1 heterodimer interacts with peptide-bound MHC-E-B2M heterotrimeric complex. KLRD1 plays a prominent role in directly interacting with MHC-E. KLRD1-KLRC1 interacts with much higher affinity with peptide-bound MHC-E-B2M than KLRD1-KLRC2. Interacts with the adapter protein TYROBP/DAP12; this interaction is required for cell surface expression and cell activation.|||Cell membrane|||Immune receptor involved in self-nonself discrimination. In complex with KLRC1 or KLRC2 on cytotoxic and regulatory lymphocyte subsets, recognizes non-classical major histocompatibility (MHC) class Ib molecule MHC-E loaded with self-peptides derived from the signal sequence of classical MHC class Ia and non-classical MHC class Ib molecules. Enables cytotoxic cells to monitor the expression of MHC class I molecules in healthy cells and to tolerate self. Primarily functions as a ligand binding subunit as it lacks the capacity to signal.|||KLRD1-KLRC1 acts as an immune inhibitory receptor. Key inhibitory receptor on natural killer (NK) cells that regulates their activation and effector functions. Dominantly counteracts T cell receptor signaling on a subset of memory/effector CD8-positive T cells as part of an antigen-driven response to avoid autoimmunity. On intraepithelial CD8-positive gamma-delta regulatory T cells triggers TGFB1 secretion, which in turn limits the cytotoxic programming of intraepithelial CD8-positive alpha-beta T cells, distinguishing harmless from pathogenic antigens. In MHC-E-rich tumor microenvironment, acts as an immune inhibitory checkpoint and may contribute to progressive loss of effector functions of NK cells and tumor-specific T cells, a state known as cell exhaustion. Upon MHC-E-peptide binding, transmits intracellular signals through KLRC1 immunoreceptor tyrosine-based inhibition motifs (ITIMs) by recruiting INPP5D/SHIP-1 and INPPL1/SHIP-2 tyrosine phosphatases to ITIMs, and ultimately opposing signals transmitted by activating receptors through dephosphorylation of proximal signaling molecules.|||KLRD1-KLRC2 acts as an immune activating receptor. On cytotoxic lymphocyte subsets recognizes MHC-E loaded with signal sequence-derived peptides from non-classical MHC class Ib MHC-G molecules, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal-fetal tolerance during pregnancy. Regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, and in particular may play a role in adaptive NK cell response to viral infection. Upon MHC-E-peptide binding, transmits intracellular signals via the adapter protein TYROBP/DAP12, triggering the phosphorylation of proximal signaling molecules and cell activation. http://togogenome.org/gene/10090:Prss33 ^@ http://purl.uniprot.org/uniprot/Q80WM7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Not glycosylated.|||Secreted|||Serine protease that has amidolytic activity, cleaving its substrates before Arg residues.|||Widely expressed. http://togogenome.org/gene/10090:Bdh2 ^@ http://purl.uniprot.org/uniprot/Q8JZV9 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) May play a role in susceptibility to bacterial infection by providing an assimilable source of iron that is exploited by pathogenic bacteria. Host iron-siderophore complexes can be used by bacteria to promote their own growth and pathogenicity.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Cytoplasm|||Detected in liver, spleen and macrophages (PubMed:24863067). Widely expressed.|||Down-regulated upon E.coli infection to limit access to host iron pool. Down-regulated in macrophages by exposure to bacterial lipopolysaccharide (LPS).|||Homotetramer.|||Mutant mice are born at the expected Mendelian frequency. They display microcytic and hypochromic anemia and iron overload in spleen and liver associated with heme toxicity when kept on high-iron diet. The plasma levels of ketone bodies is normal.|||NAD(H)-dependent dehydrogenase/reductase with a preference for cyclic substrates (By similarity). Catalyzes stereoselective conversion of 4-oxo-L-proline to cis-4-hydroxy-L-proline, likely a detoxification mechanism for ketoprolines (By similarity). Mediates the formation of 2,5-dihydroxybenzoate (2,5-DHBA), a siderophore that chelates free cytoplasmic iron and associates with LCN2, thereby regulating iron transport and homeostasis while protecting cells against free radical-induced oxidative stress. The iron-siderophore complex is imported into mitochondria, providing an iron source for mitochondrial metabolic processes in particular heme synthesis (PubMed:20550936, PubMed:24863067, PubMed:24777603). May act as a 3-hydroxybutyrate dehydrogenase (By similarity).|||Postulated to act as a 3-hydroxybutyrate dehydrogenase, however its contribution to ketone body formation appears to be physiologically irrelevant since it has very low affinity for the substrate. http://togogenome.org/gene/10090:Wfdc6b ^@ http://purl.uniprot.org/uniprot/F6ULY1 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Chtf18 ^@ http://purl.uniprot.org/uniprot/Q8BIW9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the activator 1 small subunits family. CTF18 subfamily.|||Chromosome cohesion factor involved in sister chromatid cohesion and fidelity of chromosome transmission. Component of one of the cell nuclear antigen loader complexes, CTF18-replication factor C (CTF18-RFC), which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. The CTF18-RFC complex binds to single-stranded and primed DNAs and has weak ATPase activity that is stimulated by the presence of primed DNA, replication protein A (RPA) and by proliferating cell nuclear antigen (PCNA). The CTF18-RFC complex catalyzes the ATP-dependent loading of PCNA onto primed and gapped DNA. Interacts with and stimulates DNA polymerase POLH. During DNA repair synthesis, involved in loading DNA polymerase POLE at the sites of local damage.|||Component of the CTF18-RFC complex, which consists of CTF18, CTF8, DCC1, RFC2, RFC3, RFC4 and RFC5. During assembly of the CTF18-RFC complex, CTF18 may first assemble into a subcomplex with RFC2, RFC3, RFC4 and RFC5. CTF18 then interacts directly with CTF8, which in turn interacts with DCC1. The CTF18-RFC complex associates with PCNA and with DNA polymerase POLH. The CTF18-RFC complex does not interact with the Rad9/Rad1/Hus1 complex. CTF18 interacts with SMC1A and RAD21. Interacts with DDX11.|||Nucleus http://togogenome.org/gene/10090:Uvrag ^@ http://purl.uniprot.org/uniprot/Q8K245 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with UVRAG; in the complex interacts directly with BECN1 (By similarity). PI3KC3-C2 can associate with further regulatory subunits such as RUBCN and probably SH3GLB1/Bif-1 (By similarity). Interacts with SH3GLB1; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex PI3KC3-C2 (By similarity). Interacts with RINT1 (By similarity). Associates with the NRZ complex under basal conditions and dissociates from it under autophagy conditions to associate with the PI3K complex; these complex associations seem to be mutually exclusive (By similarity). Interacts with VPS16; VPS11; VPS18; VPS33 (VPS33A or VPS33B) and VPS39; indicative for an association with a class C Vps tethering complex (possibly the HOPS complex) (By similarity). Interacts with RAB7A; RAB7A competes with UVRAG for RUBCN binding (By similarity). Interacts with STX7, VTI1B, STX8 (By similarity). Interacts with PRKDC, XRCC6 and XRCC5; indicative for an association with the DNA-dependent protein kinase complex DNA-PK (By similarity). Interacts with CEP63 (By similarity). Directly interacts with FEZ1 and SCOC; the interaction with SCOC is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1 (By similarity). Interacts with BECN1P1/BECN2 (By similarity). Interacts with SLAMF1 (PubMed:22493499). Interacts with RUBCNL/PACER; promoting targeting of UVRAG to autophagosome (By similarity). Interacts with WNK1 (By similarity).|||Early endosome|||Endoplasmic reticulum|||Involved in maintaining chromosomal stability. Promotes DNA double-strand break (DSB) repair by association with DNA-dependent protein kinase complex DNA-PK and activating it in non-homologous end joining (NHEJ). Required for centrosome stability and proper chromosome segregation.|||Late endosome|||Lysosome|||Midbody|||Phosphorylated at Ser-497 by MTOR under basal conditions; increases the interaction with RUBCN implicated in inhibitory effect of RUBCN on PI3KC3 and decreases interaction with RAB7A, and VPS16 and VPS39 (indicative for a class C Vps complex, possibly the HOPS complex) (By similarity).|||Versatile protein that is involved in regulation of different cellular pathways implicated in membrane trafficking. Involved in regulation of the COPI-dependent retrograde transport from Golgi and the endoplasmic reticulum by associating with the NRZ complex; the function is dependent on its binding to phosphatidylinositol 3-phosphate (PtdIns(3)P). During autophagy acts as regulatory subunit of the alternative PI3K complex II (PI3KC3-C2) that mediates formation of phosphatidylinositol 3-phosphate and is believed to be involved in maturation of autophagosomes and endocytosis. Activates lipid kinase activity of PIK3C3. Involved in the regulation of degradative endocytic trafficking and cytokinesis, and in regulation of ATG9A transport from the Golgi to the autophagosome; the functions seems to implicate its association with PI3KC3-C2. Involved in maturation of autophagosomes and degradative endocytic trafficking independently of BECN1 but depending on its association with a class C Vps complex (possibly the HOPS complex); the association is also proposed to promote autophagosome recruitment and activation of Rab7 and endosome-endosome fusion events. Enhances class C Vps complex (possibly HOPS complex) association with a SNARE complex and promotes fusogenic SNARE complex formation during late endocytic membrane fusion. In case of negative-strand RNA virus infection is required for efficient virus entry, promotes endocytic transport of virions and is implicated in a VAMP8-specific fusogenic SNARE complex assembly.|||autophagosome|||centromere http://togogenome.org/gene/10090:Atp5o ^@ http://purl.uniprot.org/uniprot/Q9DB20 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-162 decreases ATP production. Deacetylated by SIRT3 (By similarity).|||Acetylation of Lys-70 and Lys-158 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the ATPase delta chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or10a3b ^@ http://purl.uniprot.org/uniprot/Q8VFZ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd22 ^@ http://purl.uniprot.org/uniprot/P35329 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ B-lymphocytes.|||Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||Cell membrane|||Contains 3 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Interacts with LYN, SYK, PIK3R1/PIK3R2, PLCG1, SHC1, INPP5D and GRB2 upon phosphorylation. May form a complex with INPP5D/SHIP, GRB2 and SHC1. Interacts with PTPN6/SHP-1 upon phosphorylation (By similarity).|||Mediates B-cell B-cell interactions. May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site can be masked by cis interactions with sialic acids on the same cell surface. Upon ligand induced tyrosine phosphorylation in the immune response seems to be involved in regulation of B-cell antigen receptor signaling. Plays a role in positive regulation through interaction with Src family tyrosine kinases and may also act as an inhibitory receptor by recruiting cytoplasmic phosphatases via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules.|||Phosphorylated on tyrosine residues by LYN.|||Phosphorylation of Tyr-783 and Tyr-843 are involved in binding to SYK. Phosphorylation of Tyr-828 is involved in binding to GRB2. Phosphorylation of Tyr-863 is involved in binding to SYK, PLCG2 and PIK3R1/PIK3R2. http://togogenome.org/gene/10090:Vmn1r60 ^@ http://purl.uniprot.org/uniprot/G3UY47 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Slc7a14 ^@ http://purl.uniprot.org/uniprot/Q8BXR1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid-polyamine-organocation (APC) superfamily.|||Detected in the eyeball at 18.5 dpc. Expression increases in the retina after birth from P4 to P90.|||Expressed in retina, brain and spinal cord. In the retina, expressed in the inner nuclear layer and photoreceptor layer (at protein level) (PubMed:24670872). Expressed in liver, spleen, lung, kidney intestine and brain (at protein level) (PubMed:36640347).|||Imports 4-aminobutanoate (GABA) into lysosomes. May act as a GABA sensor that regulates mTORC2-dependent INS signaling and gluconeogenesis. The transport mechanism and substrate selectivity remain to be elucidated.|||Lysosome membrane|||Mutant mice exhibit slightly thinner retina, including outer retinal layer, and abnormal electroretinography at 2 and 6 months of age compared to wild-type animals. They are viable and fertile. They do not show any noticeable physical abnormalities.|||Up-regulated in liver in response to high-fat diet. http://togogenome.org/gene/10090:Adam30 ^@ http://purl.uniprot.org/uniprot/Q811Q3 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Arv1 ^@ http://purl.uniprot.org/uniprot/Q0VBH5|||http://purl.uniprot.org/uniprot/Q9D0U9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ARV1 family.|||Endoplasmic reticulum membrane|||Mediator of sterol homeostasis involved in sterol uptake, trafficking and distribution into membranes.|||Membrane|||Mice show an increase in the abundance of type 1 oxidative muscle fibers in the diaphragm. Female mice show also an increase in the abundance of type 1 muscle fibers in the extensor digitorum longus. Conditional knockout in neurons leads to decreased body mass; male show reduced white adipose tissue mass while female show reduced perigonadal fat mass. Show also abnormal circling behavior and severe seizures.|||Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis (PubMed:20663892). Participates in sterol transport out of the ER and distribution into plasma membranes (PubMed:20663892).|||Ubiquitous. Highly expressed in lung. http://togogenome.org/gene/10090:Usp47 ^@ http://purl.uniprot.org/uniprot/Q8BY87 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. USP47 subfamily.|||Cytoplasm|||Interacts with BTRC and FBXW11. Interacts with POLB (By similarity).|||Ubiquitin-specific protease that specifically deubiquitinates monoubiquitinated DNA polymerase beta (POLB), stabilizing POLB thereby playing a role in base-excision repair (BER) (By similarity). Acts as a regulator of cell growth and genome integrity. May also indirectly regulate CDC25A expression at a transcriptional level. http://togogenome.org/gene/10090:Tmem88b ^@ http://purl.uniprot.org/uniprot/Q3TYP4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM88 family.|||Membrane http://togogenome.org/gene/10090:Nono ^@ http://purl.uniprot.org/uniprot/Q4FK11|||http://purl.uniprot.org/uniprot/Q99K48 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA (PubMed:8355702). Also binds single-stranded DNA and RNA at a site independent of the duplex site (By similarity). Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ (By similarity). Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b (By similarity). Together with PSPC1, required for the formation of nuclear paraspeckles (By similarity). The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs (By similarity). The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1 (By similarity). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends (By similarity). In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex (By similarity). NONO is involved in transcriptional regulation (By similarity). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (By similarity). NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription (PubMed:9001221). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (PubMed:22966205). Important for the functional organization of GABAergic synapses (PubMed:26571461). Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript (PubMed:26571461). Plays a key role during neuronal differentiation by recruiting TET1 to genomic loci and thereby regulating 5-hydroxymethylcytosine levels (PubMed:32286661). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (By similarity).|||Expressed in liver and suprachiasmatic nuclei, hippocampus and neocortex (at protein level). Expression is strongest in neurons in CA1 and CA3 pyramidal regions and granule cells of the dentate gyrus. Detected in testis and kidney.|||Monomer and component of the SFPQ-NONO complex, which is probably a heterotetramer of two 52 kDa (NONO) and two 100 kDa (SFPQ) subunits. NONO is a component of spliceosome and U5.4/6 snRNP complexes (By similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Forms heterodimers with PSPC1; this involves formation of a coiled coil domain by helices from both proteins (PubMed:15140795). Part of complex consisting of SFPQ, NONO and MATR3. Part of a complex consisting of SFPQ, NONO and NR5A1. Part of a complex consisting of SFPQ, NONO and TOP1. Interacts with SPI1 and SPIB (PubMed:8626664). Interacts with RNF43 (By similarity). Interacts with PER1 and PER2 (PubMed:22966205). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA. Interacts (via second RRM domain) with WASL; the interaction is direct. Component of a multiprotein complex with WASL and SFPQ (By similarity). Interacts with ERCC6 (By similarity). Interacts (via DNA-binding domain) with TET1 (PubMed:32286661).|||Mutant mice display flattened nose and a smaller cerebellum. Behaviorally, mice show impaired spatial memory, as well as a marked anxiety phenotype and increased risk aversion (PubMed:26571461). Deletion leads to a significant dissociation of TET1 from chromatin and dysregulation of DNA hydroxymethylation of neuronal genes (PubMed:32286661).|||Nucleus|||Nucleus speckle|||nucleolus http://togogenome.org/gene/10090:Anxa10 ^@ http://purl.uniprot.org/uniprot/Q3V2F1|||http://purl.uniprot.org/uniprot/Q9D272|||http://purl.uniprot.org/uniprot/Q9QZ10 ^@ Similarity ^@ Belongs to the annexin family. http://togogenome.org/gene/10090:Cby2 ^@ http://purl.uniprot.org/uniprot/Q32MG2 ^@ Developmental Stage|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the chibby family. SPERT subfamily.|||Expressed through the elongation stage of the spermatids but absent from mature spermatozoa.|||Homodimer. Binds to NEK1.|||Testis-specific (PubMed:33536340). Expression is restricted to the flower-like structure in spermatids. http://togogenome.org/gene/10090:Gpx1 ^@ http://purl.uniprot.org/uniprot/A0A0A6YVV2|||http://purl.uniprot.org/uniprot/P11352 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutathione peroxidase family.|||Cytoplasm|||During periods of oxidative stress, Sec-47 may react with a superoxide radical, irreversibly lose hydroselenide and be converted to dehydroalanine.|||Expressed in liver, kidney and lung.|||Homotetramer. Interacts with MIEN1.|||In the absence of Sod1, Gpx1 in the liver undergoes a 40% reduction in catalytic activity as a result of the decomposition of Sec-47 to dehydroalanine.|||Mutants are healthy, fertile and show no increased sensitivity to hyperoxia.|||Number of sequencing artifacts.|||Protects the hemoglobin in erythrocytes from oxidative breakdown. In platelets, plays a crucial role of glutathione peroxidase in the arachidonic acid metabolism (PubMed:9195979).|||PubMed:2771650 sequence was originally thought to originate from human. http://togogenome.org/gene/10090:Naip5 ^@ http://purl.uniprot.org/uniprot/Q9R016 ^@ Function|||Polymorphism|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with L.pneumophila flagellin.|||(Microbial infection) Interacts with S.typhimurium (Salmonella) flagellin.|||Component of the NLRC4 inflammasome, at least composed of NLRC4, caspase-1 (CASP1) and some NAIP protein. Flagellin binding by NAIP5 triggers assembly of the inflammasome, a huge complex that contains a single NAIP5 chain and multiple copies of NLRC4 (PubMed:29182158).|||Detected in macrophages (at protein level).|||Part of the Lgn1 locus that determines susceptibility to the intracellular pathogen L.pneumophila. Susceptibility differs between inbred mouse strains. Strain C57BL/6J is not permissive, i.e. L.pneumophila cannot multiply in C57BL/6J macrophages, contrary to the situation in mouse strain A/J. Strain FVB/NJ macrophages display intermediate permissiveness for intracellular proliferation of L.pneumophila.|||Sensor component of the NLRC4 inflammasome that specifically recognizes and binds flagellin from pathogenic bacteria such as Legionella or Salmonella (PubMed:12526741, PubMed:21874021, PubMed:21918512, PubMed:29146805, PubMed:29182158). Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting caspase-1 activation, cytokine production and macrophage pyroptosis (PubMed:21874021, PubMed:21918512, PubMed:29146805, PubMed:29182158). The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri (PubMed:21874021, PubMed:21918512, PubMed:29146805, PubMed:29182158). May contribute to prevent motor-neuron apoptosis induced by a variety of signals (By similarity). http://togogenome.org/gene/10090:Mvp ^@ http://purl.uniprot.org/uniprot/E9Q3X0|||http://purl.uniprot.org/uniprot/Q3U7S9|||http://purl.uniprot.org/uniprot/Q9EQK5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Dephosphorylated by PTPN11.|||MVP 3 mediates interaction with PTEN.|||MVP 4 mediates interaction with PARP4.|||Nucleus|||Phosphorylated on Tyr residues after EGF stimulation.|||Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases (By similarity).|||Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases.|||The vault ribonucleoprotein particle is a huge (400 A x 670 A) cage structure of 12.9 MDa. It consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs). Interacts with PTEN and activated MAPK1. The phosphorylated protein interacts with the SH2 domains of PTPN11 and SRC. Interacts with APEX1 (By similarity). May interact with ZNF540 (By similarity). Interacts with TEP1. http://togogenome.org/gene/10090:Zdhhc20 ^@ http://purl.uniprot.org/uniprot/Q5Y5T1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autopalmitoylated (in vitro).|||Belongs to the DHHC palmitoyltransferase family.|||Cell membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||Highest levels in lung.|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates (PubMed:15603741). Catalyzes palmitoylation of Cys residues in the cytoplasmic C-terminus of EGFR, and modulates the duration of EGFR signaling by modulating palmitoylation-dependent EGFR internalization and degradation. Has a preference for acyl-CoA with C16 fatty acid chains. Can also utilize acyl-CoA with C14 and C18 fatty acid chains (By similarity).|||The DHHC domain is required for palmitoyltransferase activity.|||perinuclear region http://togogenome.org/gene/10090:Nkx3-1 ^@ http://purl.uniprot.org/uniprot/P97436|||http://purl.uniprot.org/uniprot/Q3UVH8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NK-3 homeobox family.|||By androgens (PubMed:8943214). During embryonic development, induced and maintained by sonic hedgehog in pre-somitic mesoderm, in immature somites and in urogenital sinus, but not in the other expression domains (PubMed:10906459).|||Defects in prostate ductal morphogenesis and secretory protein production (PubMed:10215624, PubMed:10906459). The bulbourethral gland displays prostatic epithelial hyperplasia, which increases in severity with age (PubMed:10215624, PubMed:10906459). Mice also display morphogenetic defects of minor salivary glands, which are reduced in size and exhibit severely altered duct morphology (PubMed:10906459).|||Early marker of the sclerotome and of a subset of vascular smooth muscle cells, expressed also in outgrowths of epithelial cells, in ectodermal epithelial cells and in restricted regions of the central nervous system. Detected first at 7.5 dpc in the paraxial mesoderm adjacent to the neural fold. At 8.5 dpc, segmental expression in the first 8 or 9 somites. Expression proceeds caudally in parallel with somite maturation and is restricted to the sclerotome. As the somites mature, expression moves away from the axial structures, becomes transiently restricted to a subset of early myotomal cells at the dorsal medial lip and is subsequently down-regulated. At 10.5 dpc, expressed only in the most caudal immature somites. At 9.5 dpc, present in the dorsal aorta. At 11.5 dpc, restricted to the vascular smooth muscle cells of caudal region of the dorsal aorta. At 12.5 dpc, expressed in the distal epithelium of the tongue and in Rathke pouch (anterior pituitary). By 13.5 dpc, also detected in tooth buds. Expression in the abdominal aorta continues through 11.5 to 15.5 dpc. Detected in the vertebral vessels at 12.5 dpc, in the carotid vessel at 13.5 dpc and in arcuate and interlobular arteries of the kidney at 15.5 dpc. In neonates, present in palatine glands, epithelial root sheath of the tooth and epithelial hair sheath. In the nervous system of neonates, expressed in the olfactory lobe, olfactory epithelial cells and cerebellar cortex. Expressed in the male urogenital system during late embryogenesis: at day 14.5, expressed in the outbuddings of the pelvic region of the urogenital sinus, and, at lower levels, in the prospective urethra. Expression is confined to the epithelial cells that are invaginating into the surrounding mesenchyme, with highest levels at the leading edge. At 17.5 dpc, present in the developing ventral, dorsolateral and anterior prostatic buds, in the nascent bulbourethral glands, as well as in the epithelial ducts that join the glands to the prospective urethra. During postnatal growth and morphogenesis of the prostate, high expression is maintain at sites of ductal outgrowth and branching. In the developing testis, detected at 14.5 and 17.5 dpc in the medullary cords, which form seminiferous tubules.|||Expressed mostly in the male urogenital tract, with highest expression in the epithelial cells lining the ducts of anterior, dorsolateral and ventral prostate and in the bulbourethral gland, and much lower in the seminal vesicle and the testis (PubMed:8943214, PubMed:9142502, PubMed:10215624). Expression in the prostate increases during sexual maturation and is drastically reduced following castration. Expressed also in brain (hippocampus and external granular layer of the cerebral cortex), kidney (intralobular arteries), thymus and adrenal and salivary glands (PubMed:8943214, PubMed:9142502).|||Interacts with serum response factor (SRF) (PubMed:16814806). Interacts with SPDEF. Interacts with WDR77. Interacts with TOPORS which polyubiquitinates NKX3-1 and induces its proteasomal degradation (By similarity). Interacts with FEM1B (PubMed:18816836).|||Nucleus|||Transcription factor, which binds preferentially the consensus sequence 5'-TAAGT[AG]-3' and can behave as a transcriptional repressor (By similarity). Plays an important role in normal prostate development, regulating proliferation of glandular epithelium and in the formation of ducts in prostate (PubMed:10215624). Acts as a tumor suppressor controlling prostate carcinogenesis, as shown by the ability to suppress growth and tumorigenicity of prostate carcinoma cells (PubMed:12036903). Plays a role in the formation of minor salivary glands (particularly palatine and lingual glands) (PubMed:10906459).|||Ubiquitinated by TOPORS; monoubiquitinated at several residues and also polyubiquitinated on single residues. http://togogenome.org/gene/10090:Sugp1 ^@ http://purl.uniprot.org/uniprot/Q8CH02 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the spliceosome.|||Nucleus|||Plays a role in pre-mRNA splicing. http://togogenome.org/gene/10090:Vmn1r16 ^@ http://purl.uniprot.org/uniprot/K7N775 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bbs2 ^@ http://purl.uniprot.org/uniprot/Q9CWF6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||In mice obesity is associated with hyperleptinemia and resistance to the anorectic and weight-reducing effects of leptinan mice are resistant to the metabolic actions of leptin.|||Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts (via C-terminus) with BBS7. Interacts (via coiled coil domain) with MKKS. Interacts with CCDC28B (By similarity). Interacts with DLEC1 (By similarity).|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization (By similarity).|||centriolar satellite|||cilium membrane http://togogenome.org/gene/10090:Reep4 ^@ http://purl.uniprot.org/uniprot/A0A2I3BQJ3|||http://purl.uniprot.org/uniprot/Q8K072 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DP1 family.|||Endoplasmic reticulum membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Microtubule-binding protein required to ensure proper cell division and nuclear envelope reassembly by sequestering the endoplasmic reticulum away from chromosomes during mitosis. Probably acts by clearing the endoplasmic reticulum membrane from metaphase chromosomes (By similarity). http://togogenome.org/gene/10090:Micall2 ^@ http://purl.uniprot.org/uniprot/Q3TN34 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cell projection|||Detected in brain, lung, liver and kidney (at protein level).|||Effector of small Rab GTPases which is involved in junctional complexes assembly through the regulation of cell adhesion molecules transport to the plasma membrane and actin cytoskeleton reorganization. Regulates the endocytic recycling of occludins, claudins and E-cadherin to the plasma membrane and may thereby regulate the establishment of tight junctions and adherens junctions. In parallel, may regulate actin cytoskeleton reorganization directly through interaction with F-actin or indirectly through actinins and filamins. Most probably involved in the processes of epithelial cell differentiation, cell spreading and neurite outgrowth.|||Interacts with RAB13 (GTP-bound form); competes with RAB8A and is involved in tight junctions assembly. Interacts with RAB8A; competes with RAB13 and is involved in E-cadherin endocytic recycling. Interacts with RAB8B. Interacts (preferentially in opened conformation) with ACTN1 and ACTN4; stimulated by RAB13 activation. Interacts (via calponin-homology (CH) domain) with the filamins FLNA, FLNB and FLNC (via actin-binding domain).|||Probably exists in a closed and an open conformation due to interaction of the C-terminal coiled-coil domain with an N-terminal region including the calponin-homology (CH) and the LIM zinc-binding domain. The conformational change is regulated by RAB13.|||Recycling endosome|||cytoskeleton|||cytosol|||tight junction http://togogenome.org/gene/10090:Klf17 ^@ http://purl.uniprot.org/uniprot/Q8CFA7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Exclusively expressed in testis and ovary. Localized to step 3-8 spermatids in testis and growing oocytes in ovary.|||Nucleus|||Transcription repressor that binds to the promoter of target genes and prevents their expression. Acts as a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer. Specifically binds the 5'-CACCC-3' sequence in the promoter of ID1, a key metastasis regulator in breast cancer, and repress its expression. May be a germ cell-specific transcription factor that plays important roles in spermatid differentiation and oocyte development. http://togogenome.org/gene/10090:Tdpoz8 ^@ http://purl.uniprot.org/uniprot/B7ZWN5 ^@ Similarity ^@ Belongs to the Tdpoz family. http://togogenome.org/gene/10090:Gnas ^@ http://purl.uniprot.org/uniprot/A0A571BEI3|||http://purl.uniprot.org/uniprot/P63094|||http://purl.uniprot.org/uniprot/Q6R0H6|||http://purl.uniprot.org/uniprot/Q6R0H7|||http://purl.uniprot.org/uniprot/Q9Z0F1 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the ALEX family.|||Belongs to the G-alpha family. G(s) subfamily.|||Belongs to the NESP55 family.|||Binds keratan sulfate chains.|||Cell membrane|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts through its N-terminal region with ALEX which is produced from the same locus in a different open reading frame. This interaction may inhibit its adenylyl cyclase-stimulating activity (By similarity). Interacts with MAGED2.|||Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. Stimulates the Ras signaling pathway via RAPGEF2.|||Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as Gnas isoforms.|||Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site (By similarity). Interacts with CRY1; the interaction may block GPCR-mediated regulation of cAMP concentrations. Interacts with ADCY6 and stimulates its adenylyl cyclase activity (By similarity). Interacts with ADCY2 and ADCY5 (By similarity). Stimulates the ADCY5 adenylyl cyclase activity (By similarity). Interaction with SASH1 (By similarity). Interacts with GASL2L2 (PubMed:23994616).|||Interacts with the N-terminal region of the XLas isoforms of guanine nucleotide-binding protein G(s) subunit alpha.|||It was found (PubMed:8227063) that in engineered, C3S-mutagenized sequence expressed in HEK293 cells there was no radiolabeling by either S- or N-palmitoylation. This result is incompatible with a prediction for N-palmitoylation unless N-palmitoylation depends on S-palmitoylation occurring first or N-palmitoylation did not occur in the experimental expression system.|||May be proteolytically processed to give rise to a number of active peptides.|||May inhibit the adenylyl cyclase-stimulating activity of guanine nucleotide-binding protein G(s) subunit alpha which is produced from the same locus in a different open reading frame.|||Mice cells lacking XLas isoforms which are then transfected with these isoforms and a range of receptors demonstrate that the XLas isoforms are capable of functionally coupling to the same receptors as the Gnas isoforms including Adrb2, Crfr1, Pthr1 and Tshr.|||Secreted|||Shares no sequence similarity with other isoforms (except isoform Nesp55-1) due to a novel first exon containing the entire reading frame spliced to shared exon 2 so that exons 2-13 make up the 3'-UTR.|||Shares no sequence similarity with other isoforms (except isoform Nesp55-2) due to a novel first exon containing the entire reading frame spliced to shared exon 2 so that exons 2-13 make up the 3'-UTR.|||The GNAS locus is imprinted in a complex manner, giving rise to distinct paternally, maternally and biallelically expressed proteins. The XLas isoforms are paternally derived, the Gnas isoforms are biallelically derived and the Nesp55 isoforms are maternally derived.|||This protein is produced by a bicistronic gene which also produces guanine nucleotide-binding protein G(s) subunit alpha from an overlapping reading frame.|||This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame.|||ruffle|||secretory vesicle http://togogenome.org/gene/10090:Scx ^@ http://purl.uniprot.org/uniprot/Q64124 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 6.0-6.5 dpc, expressed throughout the egg cylinder with highest expression in the epiblast. At 9.5-10.5 dpc, expressed in the lateral sclerotome and in mesenchymal cells of the limb buds and body wall. At 11.0 dpc, expressed in a metameric pattern extending along the length of the embryo. By 11.5 dpc, expression in the developing vertebrae and invertebral disks is extended caudally. High expression was seen in precursors of the ribs and bones of the limbs. Expression in progenitors of the ribs and the axial and appendicular skeleton becomes down-regulated when ossification is initiated.|||Efficient DNA binding requires dimerization with another bHLH protein. Dimerizes and binds the E-box consensus sequence with E12.|||Expressed in mesenchymal precursors of cartilage and in connective tissue. Highly expressed in tendons in the limb, tongue and diaphragm and in cartilage of the bronchi.|||Nucleus|||Plays an early essential role in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages. http://togogenome.org/gene/10090:Rrad ^@ http://purl.uniprot.org/uniprot/Q6PGA2 ^@ Similarity ^@ Belongs to the small GTPase superfamily. RGK family. http://togogenome.org/gene/10090:Gm128 ^@ http://purl.uniprot.org/uniprot/Q569E4 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ High expression in testis, but low in other tissues.|||Involved in control of cellular proliferation. Onconcogenic modifier contributing to the tumor suppressor function of DNMT3B.|||No visible phenotype. Mice lacking Ment are viable and have no overt fertility phenotype.|||Phosphorylation sites are present in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Tdrd9 ^@ http://purl.uniprot.org/uniprot/Q14BI7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-binding RNA helicase which plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:20059948, PubMed:28633017). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:20059948, PubMed:28633017). Acts downstream of piRNA biogenesis: exclusively required for transposon silencing in the nucleus, suggesting that it acts as a nuclear effector in the nucleus together with PIWIL4 (PubMed:28633017).|||Belongs to the DEAD box helicase family. DEAH subfamily.|||Cytoplasm|||Interacts with piRNA-associated proteins PIWIL1 and PIWIL4.|||Mice are viable but show male sterility with chromosome synapsis failure. In fetal testes, LINE-1 (L1) transposable elements derepression and an aberrant piRNA profile in prospermatogonia, followed by cognate DNA demethylation are observed.|||Nucleus|||Predominantly expressed in reproductive organs. Detected in mitotic spermatogonia, meiotic spermatocytes (predominantly at the pachytene stage), haploid spermatids in the testis, and in growing oocytes in the ovary (at protein level). http://togogenome.org/gene/10090:Heatr5b ^@ http://purl.uniprot.org/uniprot/Q8C547 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HEATR5 family.|||Component of clathrin-coated vesicles (By similarity). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (By similarity).|||Self-associates (By similarity). Component of the aftiphilin/p200/gamma-synergin complex, at least composed of AFTPH/aftiphilin, HEATR5B/p200a and SYNRG/gamma-synergin, which plays a role in the AP1G1/AP-1-mediated protein trafficking from early to recycling endosomes and between the trans-Golgi network (TGN) and endosomes (By similarity). Within the complex interacts with AFTPH/aftiphilin and SYNRG/gamma-synergin; the interactions are direct (By similarity). Interacts with GGA1 (By similarity).|||clathrin-coated vesicle|||perinuclear region http://togogenome.org/gene/10090:Catsperg2 ^@ http://purl.uniprot.org/uniprot/C6KI89 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation (PubMed:34225353, PubMed:19516020). Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization (PubMed:19516020).|||Belongs to the CATSPERG family.|||Catsperg2 is absent in sperm from mice lacking Catsper1, suggesting that stable expression requires Catsper1.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:21224844, PubMed:19516020). HSPA1 may be an additional auxiliary complex member (PubMed:19516020). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (Probable).|||Testis-specific. Specifically expressed in the principal piece of the sperm tail (at protein level). Expressed in spermatocytes and spermatids within the seminiferous tubule but not in interstitial cells.|||flagellum membrane http://togogenome.org/gene/10090:Zc3hc1 ^@ http://purl.uniprot.org/uniprot/Q80YV2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Essential component of a SCF-type E3 ligase complex, SCF(NIPA), a complex that controls mitotic entry by mediating ubiquitination and subsequent degradation of cyclin B1 (CCNB1). Its cell-cycle-dependent phosphorylation regulates the assembly of the SCF(NIPA) complex, restricting CCNB1 ubiquitination activity to interphase. Its inactivation results in nuclear accumulation of CCNB1 in interphase and premature mitotic entry (By similarity). Overexpression may be able to protect from apoptosis induced by IL-3 withdrawal.|||Interacts with SKP1. Component of a SCF(NIPA) E3 complex with SKP1, RBX1 and CUL1 when not phosphorylated on Ser-353. Interacts with CCNB1 (By similarity).|||Nucleus|||Phosphorylated. Phosphorylated on Ser residues at G2/M phase, but not during S and G0 phases. May also be weakly phosphorylated on Tyr residues. Ser-353 phosphorylation, a major site during the course of cell-cycle-dependent phosphorylation, results in its dissociation from the SCF(NIPA) complex, thereby preventing CCNB1 degradation leading to mitotic entry (By similarity).|||The F-box-like region is required for the interaction with SKP1. http://togogenome.org/gene/10090:Slc22a15 ^@ http://purl.uniprot.org/uniprot/Q504N2 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Contrary to human ortholog, the transport of carnitine and carnosine could not be detected.|||N-glycosylated.|||Organic zwitterion/cation transporter with apparent specificity for amino acids and their derivatives. Substrate selectivity and the transport mechanism, symport with sodium or facilitated diffusion allosterically regulated by sodium, remain to be elucidated. http://togogenome.org/gene/10090:Pir ^@ http://purl.uniprot.org/uniprot/Q9D711 ^@ Cofactor|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pirin family.|||Binds 1 Fe cation per subunit.|||Cytoplasm|||Down-regulated in mice with acute myeloid leukemias induced by either PML-RAR or AML1-ETO fusion oncoproteins.|||May interact with NF1/CTF1. Interacts with BCL3. Identified in a complex comprised of PIR, BLC3, NFKB1 and target DNA.|||Nucleus|||Quercetin is a flavonoid compound synthesized by a variety of plants, including foods for human consumption.|||Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner. May be required for efficient terminal myeloid maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase activity (in vitro).|||Weakly expressed in bone marrow. http://togogenome.org/gene/10090:Mog ^@ http://purl.uniprot.org/uniprot/Q3UY21|||http://purl.uniprot.org/uniprot/Q61885|||http://purl.uniprot.org/uniprot/Q66JM2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Do not confuse myelin-oligodendrocyte glycoprotein (MOG) with oligodendrocyte-myelin glycoprotein (OMG).|||Found exclusively in the CNS, where it is localized on the surface of myelin and oligodendrocyte cytoplasmic membranes. Reduced expression levels are observed in jimpy and quacking dysmyelinating mutant mice.|||Homodimer.|||Membrane|||Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication. Mediates homophilic cell-cell adhesion. http://togogenome.org/gene/10090:Twist2 ^@ http://purl.uniprot.org/uniprot/Q9D030 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the E-box consensus sequence 5'-CANNTG-3' as a heterodimer and inhibits transcriptional activation by MYOD1, MYOG, MEF2A and MEF2C. Also represses expression of pro-inflammatory cytokines such as TNFA and IL1B. Involved in postnatal glycogen storage and energy metabolism. Inhibits the premature or ectopic differentiation of preosteoblast cells during osteogenesis, possibly by changing the internal signal transduction response of osteoblasts to external growth factors (By similarity).|||By TNF-alpha.|||Cytoplasm|||Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3/E12. Also interacts with MEF2C.|||Expressed at low levels in sclerotome and dermatome of somites, and in limb buds at 10.5 dpc. Accumulates predominantly in dermatome, prevertebrae and derivatives of branchial arches by 13 dpc. Also expressed near surface of embryo and in chondrogenic cells. In adult, expressed at low levels in skin, bladder, uterus, aorta and heart.|||In the embryo, expression is detected at 10.5 dpc, increases continuously through to 17.5 dpc and is also high in neonates. Down-regulated in adults.|||Nucleus|||The C-terminal and HLH domains are essential for transcriptional repression. http://togogenome.org/gene/10090:Ltb4r2 ^@ http://purl.uniprot.org/uniprot/Q9JJL9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Low-affinity receptor for leukotrienes including leukotriene B4. Mediates chemotaxis of granulocytes and macrophages. The response is mediated via G-proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity). http://togogenome.org/gene/10090:Got2 ^@ http://purl.uniprot.org/uniprot/P05202 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-296, Lys-345 and Lys-363 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids.|||Cell membrane|||Detected in brain (at protein level).|||Homodimer.|||In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.|||Mitochondrion matrix http://togogenome.org/gene/10090:Fstl4 ^@ http://purl.uniprot.org/uniprot/Q5STE3 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Bcl7b ^@ http://purl.uniprot.org/uniprot/Q921K9 ^@ Function|||Similarity ^@ Belongs to the BCL7 family.|||Positive regulator of apoptosis. Plays a role in the Wnt signaling pathway, negatively regulating the expression of Wnt signaling components CTNNB1 and HMGA1 (By similarity). Involved in cell cycle progression, maintenance of the nuclear structure and stem cell differentiation (By similarity). May play a role in lung tumor development or progression. http://togogenome.org/gene/10090:Psmb2 ^@ http://purl.uniprot.org/uniprot/Q9R1P3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1B family.|||Cytoplasm|||Detected in liver (at protein level).|||Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7. http://togogenome.org/gene/10090:Cep95 ^@ http://purl.uniprot.org/uniprot/Q8BVV7 ^@ Subcellular Location Annotation ^@ centrosome|||spindle pole http://togogenome.org/gene/10090:Efna3 ^@ http://purl.uniprot.org/uniprot/O08545 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Cell membrane|||Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling.|||Expressed in myogenic progenitor cells.|||In myogenic progenitor cells, highly expressed at 11.5 dpc and ceases its expression at the late fetal stage (17.5 dpc).|||Interacts with EPHA8; activates EPHA8. http://togogenome.org/gene/10090:Trim75 ^@ http://purl.uniprot.org/uniprot/Q3UWZ0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRIM/RBCC family.|||May play a role in female meiosis.|||spindle http://togogenome.org/gene/10090:Or9s27 ^@ http://purl.uniprot.org/uniprot/Q8VET3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tex11 ^@ http://purl.uniprot.org/uniprot/Q14AT2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPO22 family.|||Chromosome|||Defects in meiotic double-strand breaks (DSBs) repair and reduced crossover formation. However, discrepancies exist between the different reports. According to a report, deletion induces male sterility (PubMed:18316482). Females are fertile with reduced litter. Adult mice show an arrest in male meiosis and aberrant chromosome segregation in anaphase spermatocytes. Chromosomal asynapsis and reduced crossover formation are observed, leading to elimination of spermatocytes at the pachytene and anaphase I stages (PubMed:18316482). According to another report, both male and female mice are fertile and produce normal-sized litters with normal Mendelian ratios (PubMed:18369460).|||In spermatocytes, not observed on asynapsed chromosomes in leptotene and appears on synapsed regions in zygotene and on the fully synapsed chromosomes in early pachytene. Disappears in late pachytene and is not observed in diplotene spermatocytes. A similar localization is detected on female meiotic chromosomes (at protein level).|||Interacts with SYCP2 (PubMed:18316482). Interacts with PBXIP1; may prevent interaction between PBXIP1 and ESR2 (PubMed:22383461). Interacts with SHOC1 (By similarity).|||Regulator of crossing-over during meiosis. Involved in initiation and/or maintenance of chromosome synapsis and formation of crossovers.|||Represent the only meiosis-specific factor encoded by the chromosome X in mouse.|||Testis-specific. http://togogenome.org/gene/10090:Cubn ^@ http://purl.uniprot.org/uniprot/Q9JLB4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Detected in yolk sac endoderm as early as day 6 and is present at the apical surface of those cells throughout the remainder of pregnancy. Apical expression is pronounced in the extraembryonic visceral endoderm (VE) of 6-9.5 dpc. Expressed by a subpopulation of cells dispersed within the 7.5 dpc embryonic endoderm and having a migratory morphology. First detected at the eight-cell stage. At the 32-cell stage expressed in all outer cells which are at the origin of the trophectoderm (TE). During the blastocyst stage, expression is predominant at the apical membrane of the TE cells.|||Endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake. Acts together with LRP2 to mediate endocytosis of high-density lipoproteins, GC, hemoglobin, ALB, TF and SCGB1A1. Acts together with AMN to mediate endocytosis of the CBLIF-cobalamin complex. Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1, APOA1, high density lipoprotein, and the CBLIF-cobalamin complex. Ligand binding requires calcium. Serves as important transporter in several absorptive epithelia, including intestine, renal proximal tubules and embryonic yolk sac. May play an important role in the development of the peri-implantation embryo through internalization of APOA1 and cholesterol. Binds to LGALS3 at the maternal-fetal interface.|||Endosome|||Expressed in kidney, thymus, ileum, placenta, small intestine and yolk sac. In kidney expressed on the apical brush border surface of proximal tubular cells, in particular in endosomes and recycling membranes vesicles, so-called dense apical tubules, which carry internalized receptors back to the cell surface. Expressed in fetal membranes of yolk sac, placenta of pregnant females.|||Interacts with AMN. Component of the cubam complex composed of one CUBN trimer and one AMN chain (By similarity). The cubam complex can dimerize (By similarity). Interacts with LRP2 in a dual-receptor complex in a calcium-dependent manner. Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and PID1/PCLI1 (By similarity).|||Lysosome membrane|||N-glycosylated.|||The CUB domains 5 to 8 mediate binding to CBLIF and ALB. CUB domains 1 and 2 mediate interaction with LRP2.|||The cubam complex is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains.|||The precursor is cleaved by a trans-Golgi proteinase furin, removing a propeptide.|||coated pit http://togogenome.org/gene/10090:Klhl22 ^@ http://purl.uniprot.org/uniprot/Q99JN2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1. Interacts with PLK1. Interacts with DEPDC5 (via DEP domain); the interaction depends on amino acid availability. Interacts with YWHAE; required for the nuclear localization of KLHL22 upon amino acid starvation.|||Lysosome|||Nucleus|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex required for chromosome alignment and localization of PLK1 at kinetochores. The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. Monoubiquitination of PLK1 does not lead to PLK1 degradation (By similarity). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway. It is therefore an amino acid-dependent activator within the amino acid-sensing branch of the TORC1 pathway, indirectly regulating different cellular processes including cell growth and autophagy (PubMed:29769719).|||centrosome|||cytosol|||spindle http://togogenome.org/gene/10090:Oat ^@ http://purl.uniprot.org/uniprot/P29758|||http://purl.uniprot.org/uniprot/Q3TG75|||http://purl.uniprot.org/uniprot/Q3UKT3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the reversible interconversion of L-ornithine and 2-oxoglutarate to L-glutamate semialdehyde and L-glutamate.|||Homohexamer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Cfap44 ^@ http://purl.uniprot.org/uniprot/E9Q5M6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CFAP44 family.|||Expressed in testis.|||Flagellar protein involved in sperm flagellum axoneme organization and function.|||Mice are viable and show no malformations. However, homozygous males exhibit complete male sterility due to severe defects in sperm mobility. Sperm from mutant mice is characterized by normal flagellum length, but most of them showed abnormal forms and irregular caliber of the midpiece. Females are fertile and give litters of normal size.|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Slc23a2 ^@ http://purl.uniprot.org/uniprot/Q9EPR4 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.|||Cell membrane|||Elevated expression levels in the adrenals of diabetic mice.|||Expressed in metabolically active and specialized tissues, including high expression in brain and adrenals. Detected in a wide range of tissues. Expression in kidney is almost undetectable.|||Interacts with CLSTN3.|||Phosphorylated.|||Sodium/ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate. http://togogenome.org/gene/10090:Rab11fip4 ^@ http://purl.uniprot.org/uniprot/Q8BQP8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a regulator of endocytic traffic by participating in membrane delivery. Required for the abcission step in cytokinesis, possibly by acting as an 'address tag' delivering recycling endosome membranes to the cleavage furrow during late cytokinesis (By similarity). May play a role in differentiation during retinal development, in a Rab11-independent manner.|||Cleavage furrow|||Cytoplasmic vesicle|||Homodimer. Forms a complex with Rab11 (RAB11A or RAB11B) and ARF6. Interacts with RAB11A; the interaction is direct. Forms a heterooligomeric complex with RAB11FIP2, RAB11FIP3 and RAB11FIP5 (By similarity). Interacts with ECPAS (By similarity).|||Midbody|||Recycling endosome membrane|||Strongly expressed in the developing retina. Expressed predominantly in neural tissues.|||The RBD-FIP domain mediates the interaction with Rab11 (RAB11A or RAB11B). http://togogenome.org/gene/10090:Rrnad1 ^@ http://purl.uniprot.org/uniprot/Q8BZG5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the METTL25 family.|||Membrane http://togogenome.org/gene/10090:Ttc3 ^@ http://purl.uniprot.org/uniprot/G5E8T2 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Copz2 ^@ http://purl.uniprot.org/uniprot/Q9JHH9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adaptor complexes small subunit family.|||COPI-coated vesicle membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||Oligomeric complex.|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex.|||cytosol http://togogenome.org/gene/10090:Ndufb4 ^@ http://purl.uniprot.org/uniprot/Q9CQC7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB4 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lrrcc1 ^@ http://purl.uniprot.org/uniprot/Q69ZB0 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LRRCC1 family.|||Contaminating sequence. Potential poly-A sequence.|||Required for the organization of the mitotic spindle. Maintains the structural integrity of centrosomes during mitosis (By similarity).|||centriole http://togogenome.org/gene/10090:Zmynd19 ^@ http://purl.uniprot.org/uniprot/Q9CQG3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in brain.|||Interacts with GPR24/MCH-R1.|||May be involved as a regulatory molecule in GPR24/MCH-R1 signaling. http://togogenome.org/gene/10090:Hsd17b2 ^@ http://purl.uniprot.org/uniprot/P51658 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the NAD-dependent oxidation of highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulates the biological potency of these steroids. Oxidizes estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity.|||Endoplasmic reticulum membrane|||Homodimer. http://togogenome.org/gene/10090:Spink7 ^@ http://purl.uniprot.org/uniprot/Q6IE32 ^@ Function|||Subcellular Location Annotation ^@ Probable serine protease inhibitor.|||Secreted http://togogenome.org/gene/10090:Map3k13 ^@ http://purl.uniprot.org/uniprot/Q1HKZ5 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by autophosphorylation and homodimerization.|||Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B (By similarity).|||Autophosphorylated on serine and threonine residues.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cytoplasm|||Homodimer; forms dimers through the leucine-zipper motif. Interacts with the C-terminus of MAPK8IP1 through the kinase catalytic domain. Binds PRDX3. Associates with the IKK complex through the kinase domain.|||Membrane http://togogenome.org/gene/10090:Apol7c ^@ http://purl.uniprot.org/uniprot/Q8C6E1 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Kcng1 ^@ http://purl.uniprot.org/uniprot/A2BDX4|||http://purl.uniprot.org/uniprot/B2RVK9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. G (TC 1.A.1.2) subfamily. Kv6.1/KCNG1 sub-subfamily.|||Cell membrane|||Heterotetramer with KCNB1.|||Membrane|||Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. http://togogenome.org/gene/10090:Rabep1 ^@ http://purl.uniprot.org/uniprot/J3QJV7|||http://purl.uniprot.org/uniprot/O35551 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the rabaptin family.|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Endosome|||Heterodimer with RABGEF1. The heterodimer binds RAB4A and RAB5A that have been activated by GTP-binding. Interacts with TSC2 (By similarity). Interacts with GGA1 (via GAE domain), GGA2 (via GAE domain) and GGA3 (via GAE domain) (By similarity). Interacts with AP1G1 (via GAE domain) (By similarity). Interacts with AP1G2 (via GAE domain) (By similarity). Interacts with ECPAS (By similarity). Interacts with KCNH1 (PubMed:22841712). Interacts with PKD1 (via C-terminal domain) and GGA1; the interactions recruit PKD1:PKD2 complex to GGA1 and ARL3 at trans-Golgi network (PubMed:25405894). Interacts with KCNH1 (By similarity).|||May be due to an intron retention.|||Proteolytic cleavage by caspases in apoptotic cells causes loss of endosome fusion activity.|||Rab effector protein acting as linker between gamma-adaptin, RAB4A and RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Involved in KCNH1 channels trafficking to and from the cell membrane. Stimulates RABGEF1 mediated nucleotide exchange on RAB5A. Mediates the traffic of PKD1:PKD2 complex from the endoplasmic reticulum through the Golgi to the cilium (PubMed:25405894).|||Recycling endosome http://togogenome.org/gene/10090:Tufm ^@ http://purl.uniprot.org/uniprot/Q8BFR5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.|||Interacts with NLRX1. Interacts with ATG16L1.|||Mitochondrion|||Promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. Also plays a role in the regulation of autophagy and innate immunity. Recruits ATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint of the RIGI-MAVS pathway. In turn, inhibits RLR-mediated type I interferon while promoting autophagy. http://togogenome.org/gene/10090:Cxcr3 ^@ http://purl.uniprot.org/uniprot/O88410 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expresses in lymphoid organs and Th1 cells.|||Homomer. Forms heteromers with ACKR4 (By similarity).|||N-glycosylated.|||Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of mesangial cells through a heterotrimeric G-protein signaling pathway. Probably promotes cell chemotaxis response (By similarity). Binds to CCL21.|||Sulfation on Tyr-27 and Tyr-29 is essential for CXCL10 binding. http://togogenome.org/gene/10090:Mok ^@ http://purl.uniprot.org/uniprot/Q9WVS4 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Able to phosphorylate several exogenous substrates and to undergo autophosphorylation (PubMed:10421840). Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner (PubMed:25243405).|||Autophosphorylated.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Highly expressed in testis, and less in kidney, brain and lung.|||Nucleus|||Phosphorylation appears to increase the enzymatic activity.|||cilium http://togogenome.org/gene/10090:Htr3a ^@ http://purl.uniprot.org/uniprot/P23979|||http://purl.uniprot.org/uniprot/Q8K1F4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3A sub-subfamily.|||Brain, spinal cord, and heart.|||Cell membrane|||Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3B or HTR3C or HTR3D or HTR3E. The homomeric complex is functional but exhibits low conductance with modified voltage dependence, and decreased agonist and antagonist affinity. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo. Interacts with RIC3.|||Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane|||The HA-stretch region of HTR3A seems to be responsible for the low conductance of HTR3A homomers compared to that of HTR3A/HTR3B heteromers. http://togogenome.org/gene/10090:Uck2 ^@ http://purl.uniprot.org/uniprot/Q543C2|||http://purl.uniprot.org/uniprot/Q99PM9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the uridine kinase family.|||Homotetramer.|||Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate. Does not phosphorylate deoxyribonucleosides or purine ribonucleosides. Can use ATP or GTP as a phosphate donor. http://togogenome.org/gene/10090:Syt16 ^@ http://purl.uniprot.org/uniprot/Q7TN83 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Highly expressed in heart and testis. Moderately expressed in kidney.|||Homodimer. Can also form heterodimers.|||May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Is Ca(2+)-independent.|||Weakly expressed at 7 dpc and remains constant from 11 dpc to 17 dpc. http://togogenome.org/gene/10090:Or5b96 ^@ http://purl.uniprot.org/uniprot/Q8VFX4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pan2 ^@ http://purl.uniprot.org/uniprot/Q8BGF7 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. PAN2 subfamily.|||Binds 2 metal cations per subunit in the catalytic exonuclease domain.|||Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenylation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1 (PubMed:16284618). Also acts as an important regulator of the HIF1A-mediated hypoxic response. Required for HIF1A mRNA stability independent of poly(A) tail length regulation (By similarity).|||Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex.|||Forms a heterotrimer with an asymmetric homodimer of the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex (By similarity). Interacts with PAN3 isoform 1/Pan3L and isoform 3/Pan3S (By similarity). Interacts with ZFP36 (PubMed:21078877).|||Nucleus|||P-body|||Positively regulated by the regulatory subunit PAN3.|||The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3. http://togogenome.org/gene/10090:Crisp1 ^@ http://purl.uniprot.org/uniprot/Q03401|||http://purl.uniprot.org/uniprot/Q545H0 ^@ Caution|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CRISP family.|||By androgens.|||Exponential increase between days 25 and 30 after birth.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mainly found in the cauda epididymis where it is synthesized by the principal cells and secreted into the lumen. Binds to the heads of spermatozoa. Also expressed in the submandibular gland.|||This protein is supposed to help spermatozoa undergo functional maturation while they move from the testis to the ductus deferens.|||secretory vesicle http://togogenome.org/gene/10090:Ptprs ^@ http://purl.uniprot.org/uniprot/B0V2N1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cleavage occurs, separating the extracellular domain from the transmembrane segment. This process called 'ectodomain shedding' is thought to be involved in receptor desensitization, signal transduction and/or membrane localization (By similarity).|||Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.|||Binding to large heparan sulfate proteoglycan structures promotes oligomerization (PubMed:21454754). Binding to chondroitin sulfate proteoglycan does not lead to oligomerization (PubMed:21454754). Interacts (via Ig-like domains) with NTRK3 (PubMed:25385546). Interacts (via Ig-like domains) with NTRK1, but does not form detectable complexes with NTRK2 (By similarity). Interacts with PPFIA1, PPFIA2 and PPFIA3 (By similarity).|||Cell membrane|||Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycans (PubMed:19833921, PubMed:21454754, PubMed:22406547). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth (PubMed:21454754). Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection (PubMed:15797710, PubMed:19833921, PubMed:19780196, PubMed:21454754, PubMed:22519304, PubMed:22406547). Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2 (PubMed:21454754). Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb (PubMed:10080191). Functions as tyrosine phosphatase (PubMed:7529177). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (By similarity). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases (PubMed:15797710). Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (PubMed:26231120).|||Detected in brain cortex, cerebellum and thoracic spinal cord (at protein level) (PubMed:19780196, PubMed:22519304). Detected in motor cortex and white matter of the spinal cord, but not in spinal cord gray matter (PubMed:19780196). Isoform 1 and isoform 6 are predominantly expressed in the brain (cerebrum and cerebellum) and to a lesser extent in the heart and skeletal muscle. Also found in neuronal-derived cell lines (PubMed:7529177). Detected in the ganglion cell layer of the retina and in glial cells along the optic nerve (PubMed:15797710). Detected in bone marrow and spleen plasmacytoid dendritic cells (PubMed:26231120).|||Expression is seen in embryos between 8 dpc and 16 dpc and a peak expression is seen at 14 dpc.|||Mating heterozygous mice gives rise to Ptprs deficient mice at the expected Mendelian rate, but the pups are somewhat lighter than their littermates at birth and display strongly impaired weight gain (PubMed:10080191). After about three weeks, mutant mice weigh only 50 to 55% of normal littermates, possibly due to reduced Igf1 levels in blood serum (PubMed:10080191). Pups born after crossing Ptprs deficient mice display about 41% lethality during the first day after birth (PubMed:10080191). Adult mutants have a reduced overall brain size, with a dramatic decrease in the size of the olfactory bulb (PubMed:10080191). As a consequence, mutant mice have strongly impaired ability to perceive repellent smells (PubMed:10080191). Females are less often in estrus (PubMed:10080191). Besides, mutant mice display a decreased overall size of the pituitary glands; relative to the total size, the intermediary lobe is enlarged with a concomitant decrease in the size of the anterior and posterior lobes (PubMed:10080191). Likewise, the size of the hypothalamus is decreased (PubMed:10080191). No visible effect on the structure of the retina and the optic nerve (PubMed:15797710). Mutant mice show increased axon outgrowth from retinal ganglion cells after optic nerve transection (PubMed:15797710). Mutant mice display increased axon outgrowth after spinal cord injury (PubMed:19833921, PubMed:19780196). In aging mice, mossy fibers in the CA3C region of the hippocampus show increased sprouting (PubMed:22519304). No difference in mossy fiber sprouting is seen in the CA3A region of the hippocampus (PubMed:22519304). After kainate-induced seizures, mutant mice show increased mossy fiber sprouting in both the CA3C and the CA3A region of the hippocampus (PubMed:22519304). Mutant mice display a slight increase in dendrite length and dendrite spine density in pyramidal cells in the CA1 region of the hippocampus, and subtle changes in miniature AMPAR-mediated excitatory post-synaptic currents (PubMed:22519304). Dorsal root ganglion neurons from mutant mice show decreased stimulation of neurite outgrowth in response to the heparan sulfate proteoglycan GPC2 (PubMed:21454754). Cerebellar granule neurons and dorsal root ganglion neurons from mutant mice show decreased inhibition of neurite outgrowth in response to chondroitin sulfate proteoglycan (PubMed:19833921, PubMed:19780196, PubMed:21454754, PubMed:22406547). Sensory neurons show increased axon outgrowth after spinal cord crush injury (PubMed:19833921). After optic nerve crush injury, mutant mice show no increase in axon regeneration (PubMed:22406547). Combined disruption of Rtn4r, Rtn4rl1 and Ptprs increases axon regeneration after injury (PubMed:22406547).|||Perikaryon|||Postsynaptic density|||axon|||growth cone|||neuron projection|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Stard3nl ^@ http://purl.uniprot.org/uniprot/A0A0G2JE93|||http://purl.uniprot.org/uniprot/Q9DCI3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STARD3 family.|||Homodimer. Interacts (via the MENTAL domain) with STARD3NL. Interacts (via FFAT motif) with VAPA. Interacts (via FFAT motif) with VAPB. Interacts (via FFAT motif) with MOSPD2 (via MSP domain).|||Late endosome membrane|||Membrane|||Tethering protein that creates contact site between the endoplasmic reticulum and late endosomes: localizes to late endosome membranes and contacts the endoplasmic reticulum via interaction with VAPA and VAPB.|||The FFAT motif mediates interaction with VAPA, VAPB and MOSPD2.|||The MENTAL domain anchors the protein in endosome membranes and exposes the START domain in the cytosol (By similarity). It binds cholesterol and mediates homotypic as well as heterotypic interactions between STARD3 and STARD3NL (By similarity). http://togogenome.org/gene/10090:Dnal4 ^@ http://purl.uniprot.org/uniprot/Q9DCM4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynein light chain family.|||Consists of at least two heavy chains and a number of intermediate and light chains.|||Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity (By similarity).|||cilium axoneme http://togogenome.org/gene/10090:Chpf2 ^@ http://purl.uniprot.org/uniprot/Q3UU43 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Golgi stack membrane|||Membrane http://togogenome.org/gene/10090:Ddx3y ^@ http://purl.uniprot.org/uniprot/Q62095 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.|||Cytoplasm|||Found in heart, brain, liver, skeletal muscle, kidney and testis. Low expression detected in lung. In testis, expressed in all types of spermatogenic cells including spermatogonia, spermatocytes, spermatids and somatic Sertoli cells within the seminiferous tubules. Also expressed in Leydig cells and other interstitial cells.|||Knockout males show normal spermatogenesis, produce morphologically normal spermatozoa and sire healthy offspring (PubMed:30613052). DDX3X and DDX3Y double knockout is embryonic lethal (PubMed:30613052). DDX3X and DDX3Y double knockout germ cells can differentiate into spermatozoa (PubMed:30613052).|||Nucleus|||Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway (PubMed:30475900). http://togogenome.org/gene/10090:Or4a80 ^@ http://purl.uniprot.org/uniprot/A2AUA2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dnmt3b ^@ http://purl.uniprot.org/uniprot/O88509|||http://purl.uniprot.org/uniprot/Q3KR45|||http://purl.uniprot.org/uniprot/Q541E5 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by binding to the regulatory factor DNMT3L.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.|||Citrullinated by PADI4.|||Expressed in almost all blastocysts at 3.0 dpc. Preferentially expressed in the trophectoderm (TE) in 3.5 dpc and polar TE in 4.0 dpc blastocysts. In 4.5 dpc embryos, expressed in the polar TE and some inner cell mass (ICM) embryonic lineage cells. In post-implantation embryo at 5.5 dpc, expressed in the epiblast (embryonic lineage) derived from the ICM. Highly expressed, at 7.5 dpc, in the embryonic ectoderm, neural ectoderm, and chorionic ectoderm; a weak expression is also detected in mesodermal and endodermal cells. At later stages, the expression is detected predominantly in the forebrain and eyes but weakly throughout the embryo.|||Interacts with CBX4, DNMT1, DNMT3A, SETDB1, UBE2I9, UBL1 and ZHX1 (By similarity). Interacts with SUV39H1 and BAZ2A/TIP5. Interacts with the PRC2/EED-EZH2 complex. Interacts with UHRF1.|||Nucleus|||Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing. In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Functions as a transcriptional corepressor by associating with ZHX1 (By similarity). Required for DUX4 silencing in somatic cells (By similarity).|||Sumoylated.|||The PWWP domain is essential for targeting to pericentric heterochromatin. http://togogenome.org/gene/10090:Nadk2 ^@ http://purl.uniprot.org/uniprot/Q8C5H8|||http://purl.uniprot.org/uniprot/Q9CUB4 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD kinase family.|||Homodimer.|||Inhibited by NADH, NADPH and NADP(+).|||Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Fabp9 ^@ http://purl.uniprot.org/uniprot/O08716 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Testis. http://togogenome.org/gene/10090:Stard13 ^@ http://purl.uniprot.org/uniprot/F8WIY7|||http://purl.uniprot.org/uniprot/Q923Q2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Interacts with TAX1BP1 (By similarity).|||Lipid droplet|||May function as a GTPase-activating protein.|||Membrane|||Mitochondrion membrane http://togogenome.org/gene/10090:Aldh1a7 ^@ http://purl.uniprot.org/uniprot/B2RTL5|||http://purl.uniprot.org/uniprot/O35945 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Can oxidize benzaldehyde, propionaldehyde and acetaldehyde (By similarity). No detectable activity with retinal.|||Cytoplasm|||Highest level in liver, high level in lung, low level in kidney and testis.|||Homotetramer.|||Xenopus embryos injected with Aldh1a7 mRNA failed to produce retinoic acid in contrast to embryos injected with Aldh1a1. http://togogenome.org/gene/10090:Cpt1c ^@ http://purl.uniprot.org/uniprot/Q8BGD5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the carnitine/choline acetyltransferase family.|||Endoplasmic reticulum|||May play a role in lipid metabolic process.|||Mitochondrion outer membrane|||Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including CPT1C. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing. Interacts with ATL1 (By similarity).|||Predominantly expressed in brain (at protein level) and testis. Expressed in motor neurons (PubMed:25751282). Expressed in the ventral horn from spinal cords (PubMed:25751282).|||Synapse|||axon|||dendrite http://togogenome.org/gene/10090:Plekhg5 ^@ http://purl.uniprot.org/uniprot/Q66T02 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals develop normally and show no clear neurologic symptoms as adults. However, electrophysiologic studies indicated that mutant mice have decreased motor nerve conduction velocities and delayed compound action potentials. Mutant mice perform slightly less well than control mice in the rotarod test (PubMed:23777631). Deficient mice have no motoneuron loss during their first year. A loss of motoneurons starts at 12 months and this decrease is more prominent in 24-month-old animals. Biogenesis of autophagosomes is impaired in Plekhg5-deficient motoneurons resulting in a reduced number of retrogradely transported autophagosomes (PubMed:29084947).|||Cell junction|||Cell membrane|||Cytoplasm|||Expressed in neurons and glial cells of the peripheral nervous system, with highest levels of expression in the brain and sciatic nerve endoneurium. Isoform 2 is expressed at detectable levels only in malignant cells.|||Functions as a guanine exchange factor (GEF) for RAB26 and thus regulates autophagy of synaptic vesicles in axon terminal of motoneurons (PubMed:29084947). Involved in the control of neuronal cell differentiation. Plays a role in angiogenesis through regulation of endothelial cells chemotaxis (PubMed:21543326). Affects also the migration, adhesion, and matrix/bone degradation in macrophages and osteoclasts (By similarity).|||Interacts with GIPC1/synectin and RHOA.|||Regulated during development, with the highest level at postnatal days 10 to 14, suggesting a role in myelination of the peripheral nervous system.|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Sf3a2 ^@ http://purl.uniprot.org/uniprot/G3UVU2|||http://purl.uniprot.org/uniprot/Q7TN25 ^@ Similarity ^@ Belongs to the SF3A2 family. http://togogenome.org/gene/10090:Ppef2 ^@ http://purl.uniprot.org/uniprot/O35385 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Tissue Specificity ^@ Activated by calcium.|||Belongs to the PPP phosphatase family.|||Binds 2 manganese ions per subunit.|||Detected in retina, more specifically in photoreceptors.|||May play a role in phototransduction. May dephosphorylate photoactivated rhodopsin. May function as a calcium sensing regulator of ionic currents, energy production or synaptic transmission. http://togogenome.org/gene/10090:Tsr2 ^@ http://purl.uniprot.org/uniprot/H7BWY8|||http://purl.uniprot.org/uniprot/Q8C8T8|||http://purl.uniprot.org/uniprot/Z4YL87 ^@ Function|||Similarity ^@ Belongs to the TSR2 family.|||May be involved in 20S pre-rRNA processing. http://togogenome.org/gene/10090:Adgrl1 ^@ http://purl.uniprot.org/uniprot/H7BX15|||http://purl.uniprot.org/uniprot/Q80TR1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoproteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit. This proteolytic processing takes place early in the biosynthetic pathway, either in the endoplasmic reticulum or in the early compartment of the Golgi apparatus.|||Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Calcium-independent receptor of high affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells (PubMed:35907405). Receptor for TENM2 that mediates heterophilic synaptic cell-cell contact and postsynaptic specialization. Receptor probably implicated in the regulation of exocytosis (By similarity).|||Cell membrane|||Forms a heterodimer, consisting of a large extracellular region (p120) non-covalently linked to a seven-transmembrane moiety (p85). Interacts with syntaxin and with proteins of the SHANK family via the PDZ domain (By similarity). Interacts (via extracellular domain) with FLRT1, FLRT2 and FLRT3 (via extracellular domain) (PubMed:22405201).|||Knockout animals are born at sub-Mendelian ratios. ADGRL1-null mice who survive to adulthood demonstrate stereotypic behaviors, sexual dysfunction, bimodal extremes of locomotion, augmented startle reflex, and attenuated pre-pulse inhibition, which respond to risperidone. Ex vivo synaptic preparations display increased spontaneous exocytosis of dopamine, acetylcholine, and glutamate, although ADGRL1-deficient neurons poorly form synapses in vitro.|||Membrane|||Presynaptic cell membrane|||Synapse|||The extracellular domain coupled to the a single transmembrane region are sufficient for full responsiveness to alpha-latrotoxin.|||axon|||growth cone|||synaptosome http://togogenome.org/gene/10090:Or5af1 ^@ http://purl.uniprot.org/uniprot/Q7TRZ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem165 ^@ http://purl.uniprot.org/uniprot/P52875 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GDT1 family.|||Expressed in mammary epithelial cells (at protein level).|||Expressed in undifferentiated mouse F9 teratocarcinoma stem cells but disappearing rapidly after treatment with a tumor-promoting phorbol ester.|||Golgi apparatus membrane|||Putative divalent cation:proton antiporter that exchanges calcium or manganese ions for protons across the Golgi membrane. Mediates the reversible transport of calcium or manganese to the Golgi lumen driven by the proton gradient and possibly the membrane potential generated by V-ATPase. Provides calcium or manganese cofactors to resident Golgi enzymes and contributes to the maintenance of an acidic luminal Golgi pH required for proper functioning of the secretory pathway (By similarity). Promotes Ca(2+) storage within the Golgi lumen of the mammary epithelial cells to be then secreted into milk (PubMed:30622138). The transport mechanism and stoichiometry remains to be elucidated (By similarity). http://togogenome.org/gene/10090:Snx5 ^@ http://purl.uniprot.org/uniprot/Q9D8U8 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sorting nexin family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle membrane|||Detected in macrophages (at protein level).|||Early endosome|||Early endosome membrane|||Endosome|||Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2; does not homodimerize. The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C. Interacts with HGS; increased by PIP5K1C kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2 (By similarity).|||Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol lipids. Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin. Plays a role in the internalization of EGFR after EGF stimulation. Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C and is retromer-independent. Together with PIP5K1C facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By similarity). Plays a role in macropinocytosis (PubMed:18854019).|||The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (By similarity).|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.|||The selectivity for particular phosphatidylinositol lipids is under debate. According to one report (PubMed:19553671), the rat protein binds exclusively to phosphatidylinositol 4,5-bisphosphate, while the human protein has been reported (PubMed:15561769) to bind to phosphatidylinositol 3,4-bisphosphate and also to phosphatidylinositol 3-phosphate.|||phagocytic cup|||ruffle http://togogenome.org/gene/10090:Ghitm ^@ http://purl.uniprot.org/uniprot/Q91VC9 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BI1 family.|||By growth hormone.|||Interacts with LETM1 and AFG3L2.|||Mitochondrion inner membrane|||Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (PubMed:35715207). Mediates proton-dependent calcium efflux from mitochondrion (By similarity). Functions also as an electroneutral mitochondrial proton/potassium exchanger (PubMed:35715207). Required for the mitochondrial tubular network and cristae organization (PubMed:35715207). Involved in apoptotic release of cytochrome c (By similarity). Inhibits AFG3L2 proteolytic activity, stimulating respiration and stabilizing respiratory enzymes in actively respiring mitochondria (By similarity). However, when mitochondria become hyperpolarized, GHITM loses its inhibitory activity toward AFG3L2 and the now active AFG3L2 turns first on GHITM and, if hyperpolarization persists, on other proteins of the mitochondria, leading to a broad remodeling of the mitochondrial proteome (By similarity).|||Undergoes AFG3L2-mediated proteolytic degradation, upon hyperpolarization of mitochondria. http://togogenome.org/gene/10090:Or52ab2 ^@ http://purl.uniprot.org/uniprot/L7N224 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defa34 ^@ http://purl.uniprot.org/uniprot/D3Z0J0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Eva1c ^@ http://purl.uniprot.org/uniprot/A0A338P750|||http://purl.uniprot.org/uniprot/P58659|||http://purl.uniprot.org/uniprot/Q8CAX0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the EVA1 family.|||Binds heparin.|||Cell membrane|||Ubiquitous. http://togogenome.org/gene/10090:Nat8f5 ^@ http://purl.uniprot.org/uniprot/Q9QXS8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||May play a role in regulation of gastrulation.|||Membrane http://togogenome.org/gene/10090:Pnpla7 ^@ http://purl.uniprot.org/uniprot/A2AJ88 ^@ Activity Regulation|||Caution|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NTE family.|||By nutritional conditions (PubMed:22326266, PubMed:18086666). Expression of isoform 3 is switched to the expression of isoform 2 during fasting (PubMed:22326266).|||Endoplasmic reticulum membrane|||Expressed in white adipose tissue, cardiac muscle, skeletal muscle, and testis.|||Expressed in white and brown adipose tissue, cardiac muscle, skeletal muscle, and testis.|||Expression levels are not affected by fasting.|||In white adipose tissue, cardiac muscle, skeletal muscle, and testis, expression levels are down-regulated under well-fed conditions and are up-regulated during fasting.|||In white adipose tissue, cardiac muscle, skeletal muscle, and testis, expression levels are up-regulated under well-fed conditions and are down-regulated during fasting.|||Intron retention.|||It is uncertain whether Met-1 or Met-27 is the initiator.|||Lacks lysophospholipase activity.|||Lipid droplet|||Lysophospholipase which preferentially deacylates unsaturated lysophosphatidylcholine (C18:1), generating glycerophosphocholine (PubMed:18086666, PubMed:28887301). Can also deacylate, to a lesser extent, lysophosphatidylethanolamine (C18:1), lysophosphatidyl-L-serine (C18:1) and lysophosphatidic acid (C16:0) (PubMed:22326266, PubMed:18086666, PubMed:28887301).|||Lysophospholipase.|||The 3 cNMP binding domains are required for localization to the endoplasmic reticulum (PubMed:28887301). The cNMP binding domain 3 is involved in the binding to lipid droplets (PubMed:28887301).|||cAMP does not regulate lysophospholipase activity in vitro (PubMed:18086666, PubMed:28887301). Slightly inhibited by organophosphorus (OP) compounds such as mipafox, which is likely why mice are less sensitive to distal axonophathy induced by OPs compared to humans (PubMed:18086666). http://togogenome.org/gene/10090:Nr6a1 ^@ http://purl.uniprot.org/uniprot/Q64249 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR6 subfamily.|||Expressed in the germ cells of both the adult testis and ovary, being most abundant in spermatids.|||Homodimer. Interacts with UIMC1.|||Nucleus|||Orphan nuclear receptor. Binds to a response element containing the sequence 5'-TCAAGGTCA-3'. May be involved in the regulation of gene expression in germ cell development during gametogenesis. http://togogenome.org/gene/10090:Zhx3 ^@ http://purl.uniprot.org/uniprot/Q3UPQ8|||http://purl.uniprot.org/uniprot/Q8C0Q2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. Involved in the early stages of mesenchymal stem cell (MSC) osteogenic differentiation. Is a regulator of podocyte gene expression during primary glomerula disease. Binds to promoter DNA.|||Belongs to the ZHX family.|||Homodimer (via homeobox domain 1). Heterodimer with ZHX1 (via homeobox domain 1). Heterodimer with ZHX2 (via homeobox domain 1). Heterodimerization with ZHX1 is a prerequisite for repressor activity. Interacts with NFYA.|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Aftph ^@ http://purl.uniprot.org/uniprot/Q80WT5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of clathrin-coated vesicles (By similarity). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (By similarity).|||Cytoplasm|||Self-associates (By similarity). Interacts with GGA1 (via GAE domain) (By similarity). Interacts with GGA3 (via GAE domain), AP1G1 (via GAE domain) and AP1G2 (via GAE domain) (By similarity). Component of the aftiphilin/p200/gamma-synergin complex, at least composed of AFTPH/aftiphilin, HEATR5B/p200a and SYNRG/gamma-synergin, which plays a role in the AP1G1/AP-1-mediated protein trafficking from early to recycling endosomes (By similarity). Within the complex interacts with HEATR5B/p200a and SYNRG/gamma-synergin; the interactions are direct (By similarity). Interacts with AP1G1/AP-1; the interaction is required to recruit AFTPH/aftiphilin to the perinuclear region of the cell (By similarity). Interacts with CLTCL1/Clathrin (By similarity).|||The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself (By similarity).|||clathrin-coated vesicle|||perinuclear region http://togogenome.org/gene/10090:Scgb2b18 ^@ http://purl.uniprot.org/uniprot/A0A087WPA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Pradc1 ^@ http://purl.uniprot.org/uniprot/Q9D9N8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in metabolically active tissues such as liver, muscle, adipose, and heart and different brain regions like cortex and hypothalamus, expression is acutely regulated by the nutritional state.|||Expression in metabolically active tissues is significantly suppressed by refeeding.|||Mutants born at the expected Mendelian ratio, and they appear normal with no gross developmental abnormalities (PubMed:31689374). Knockout female mice fed with high fat diet have reduced weight gain by elevating physical activity and energy expenditure (PubMed:31689374).|||N-glycosylated; required for efficient secretion.|||Plays a role in the modulation of physical activity and adiposity.|||Secreted http://togogenome.org/gene/10090:Or11h7 ^@ http://purl.uniprot.org/uniprot/E9Q840 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cdc37 ^@ http://purl.uniprot.org/uniprot/Q61081 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDC37 family.|||Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity. Inhibits HSP90AA1 ATPase activity (By similarity).|||Constitutively sumoylated by UBE2I.|||Cytoplasm|||Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2 (By similarity). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Forms a complex with Hsp90/HSP90AB1 and CDK6 (By similarity). Interacts with HSP90AA1 (By similarity). Interacts with AR, CDK4, CDK6 and EIF2AK1 (By similarity). Interacts with RB1 (By similarity). Interacts with KSR1 (PubMed:10409742). Interacts with FLCN, FNIP1 and FNIP2 (By similarity). http://togogenome.org/gene/10090:Plcxd2 ^@ http://purl.uniprot.org/uniprot/B2RXA1 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at highest levels in brain, followed by stomach and small intestine. Detected at low levels in kidney, ey, thymus and slkeletal muscle.|||Nucleus http://togogenome.org/gene/10090:Pitx3 ^@ http://purl.uniprot.org/uniprot/O35160 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||First visible in 10.5 dpc embryos where expression is confined to the lens vesicles. Between 11.5 dpc and 12.5 dpc, expressed in both the lens epithelium and differentiating primary fiber cells. In the late fetal stage after the lens is formed, primarily found in the lens epithelium and the lens equator region where lens epithelial cells exit from the cell cycle and differentiate into fiber cells (at protein level). First expressed in the eye at 10 dpc embryos. Throughout eye development, expressed in the lens placode and forming lens pit. From 12 dpc, also detected in the midbrain region, tongue, incisor primordia, condensing mesenchyme around the sternum and vertebrae and in the head muscles.|||Highly expressed in developing eye lens. Expression is restricted to the substantia nigra and ventral tegmental area in the midbrain.|||Interacts with SFPQ.|||Mice show loss of nascent substantia nigra dopaminergic neurons at the beginning of their final differentiation and a loss of tyrosine hydroxylase (TH) expression specifically in the substantia nigra neurons.|||Mutations in Pitx3 appear to be the cause of the aphakia (ak) phenotype, a recessive homozygous disease characterized by small eyes and closed eyelids.|||Nucleus|||Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. In addition to its importance during development, it also has roles in the long-term survival and maintenance of the mdDA neurons. Activates NR4A2/NURR1-mediated transcription of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons. Acts by decreasing the interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT which acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state. Essential for the normal lens development and differentiation. Plays a critical role in the maintenance of mitotic activity of lens epithelial cells, fiber cell differentiation and in the control of the temporal and spatial activation of fiber cell-specific crystallins. Positively regulates FOXE3 expression and negatively regulates PROX1 in the anterior lens epithelium, preventing activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2 and thus maintains lens epithelial cells in cell cycle. http://togogenome.org/gene/10090:Ap1g1 ^@ http://purl.uniprot.org/uniprot/P22892|||http://purl.uniprot.org/uniprot/Q8CBB7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3) (By similarity). Interacts (via GAE domain) with RABEP1 (By similarity). Interacts with EPS15 (PubMed:12176391). Interacts with SYNRG/gamma-synergin (PubMed:12176391). Interacts (via GAE domain) with AP1AR (via coiled-coil domain) (By similarity). Interacts with CLN3 (via dileucine motif); this interaction facilitates lysosomal targeting (By similarity). Interacts (via GAE domain) with AFTPH/aftiphilin; the interaction is required to recruit AFTPH/aftiphilin to the perinuclear region of the cell (By similarity).|||Belongs to the adaptor complexes large subunit family.|||Cytoplasm|||Golgi apparatus|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. In association with AFTPH/aftiphilin in the aftiphilin/p200/gamma-synergin complex, involved in the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (By similarity).|||Widely expressed.|||clathrin-coated pit|||clathrin-coated vesicle|||clathrin-coated vesicle membrane|||perinuclear region http://togogenome.org/gene/10090:Igbp1b ^@ http://purl.uniprot.org/uniprot/A0A0B4J1F7 ^@ Similarity ^@ Belongs to the IGBP1/TAP42 family. http://togogenome.org/gene/10090:Or5m9b ^@ http://purl.uniprot.org/uniprot/Q7TR85 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gck ^@ http://purl.uniprot.org/uniprot/P52792|||http://purl.uniprot.org/uniprot/Q5SVI5|||http://purl.uniprot.org/uniprot/Q5SVI6 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the hexokinase family.|||Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively) (PubMed:8530440). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant (By similarity). Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues (PubMed:8530440, PubMed:9867845). Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell (PubMed:8530440, PubMed:9867845). In pancreas, plays an important role in modulating insulin secretion (PubMed:8530440). In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage (PubMed:9867845). Required to provide D-glucose 6-phosphate for the synthesis of glycogen (PubMed:9867845). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity).|||Cytoplasm|||Embryonic lethality caused by the absence of hexokinase activity (PubMed:7665557). Conditional deletion in pancreatic beta-cells causes severe diabetes shortly after birth leading to lethality within a week (PubMed:8530440, PubMed:9867845). Deficient islets show defective insulin secretion in response to glucose (PubMed:8530440). Conditional deletion in liver leads to mild hyperglycemia; however, mice display pronounced defects in both glycogen synthesis and glucose turnover rates during a hyperglycemic clamp (PubMed:9867845).|||Mitochondrion|||Monomer (By similarity). Interacts with MIDN; the interaction occurs preferentially at low glucose levels and results in inhibition of hexokinase activity (By similarity). Interacts with GCKR; leading to sequestration in the nucleus (PubMed:10713097).|||Nucleus|||Subject to allosteric regulation. Low glucose and high fructose-6-phosphate triggers association with the inhibitor GCKR followed by sequestration in the nucleus.|||Up-regulated by endocannabinoid anandamide/AEA. http://togogenome.org/gene/10090:Fpgt ^@ http://purl.uniprot.org/uniprot/G5E8F4 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Catalyzes the formation of GDP-L-fucose from GTP and L-fucose-1-phosphate (PubMed:14686921). Functions as a salvage pathway to reutilize L-fucose arising from the turnover of glycoproteins and glycolipids (Probable).|||Cytoplasm|||Expressed at highest levels in brain, moderately in testis, ovary and kidney, and weakly in liver, spleen, heart and lung. http://togogenome.org/gene/10090:Cyp2d22 ^@ http://purl.uniprot.org/uniprot/Q9JKY7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Hscb ^@ http://purl.uniprot.org/uniprot/A0A0R4J0T0|||http://purl.uniprot.org/uniprot/Q8K3A0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain. Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20 (By similarity). Plays an essential role in hematopoiesis (PubMed:32634119).|||Acts as a co-chaperone in iron-sulfur cluster assembly in the cytoplasm. Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1. This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT.|||Belongs to the HscB family.|||Cytoplasm|||Homodimer. Interacts with ISCU (cytoplasmic form); this interaction stabilzes the (Fe-S) clusters on ISCU. Interacts with the CIA complex member CIAO1 (via LYR motif).|||Interacts with ISCU and HSPA9 to form an iron-sulfur transfer complex. Interacts with SDHAF1 (via the first LYR motif); the interaction recruits the iron-sulfur transfer complex composed of HSC20, HSPA9 and ISCU and mediates the incorporation of iron-sulfur clusters into SDHB which also interacts with HSC20. Interacts with the cytoplasmic form of ISCU and with CIA complex member CIAO1 (via LYR motif).|||Knockout of the gene is embryonic lethal. Specific loss of the gene in erythroblasts is also lethal due to anemia.|||Mitochondrion http://togogenome.org/gene/10090:Ablim1 ^@ http://purl.uniprot.org/uniprot/E9Q030|||http://purl.uniprot.org/uniprot/E9Q9C0|||http://purl.uniprot.org/uniprot/E9Q9C1|||http://purl.uniprot.org/uniprot/E9Q9C7|||http://purl.uniprot.org/uniprot/E9Q9D1|||http://purl.uniprot.org/uniprot/E9QK41|||http://purl.uniprot.org/uniprot/Q3UP03|||http://purl.uniprot.org/uniprot/Q8K4G5 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds F-actin. Interacts with ABRA (By similarity).|||Cytoplasm|||Isoform 1 is detected at low levels starting from 12 dpc and remains constant until birth. After this levels increase strongly and expression remains high in adults. Isoform 2 and isoform 3 are expressed at a constant high level throughout development.|||Isoform 1 is detected in adult retina, where it is highly expressed in the ganglion layer. Detected in rod inner segment. Isoform 2 is highly expressed in adult retina, brain, kidney and heart. Isoform 3 is highly expressed in adult retina, brain, kidney, liver, skeletal muscle, spleen and heart. Detected in embryonic retina, brain, spinal cord, peripheral sensory ganglia and thymus.|||Isoform 1 is not necessary for normal axon guidance.|||May act as scaffold protein (By similarity). May play a role in the development of the retina. Has been suggested to play a role in axon guidance.|||cytoskeleton http://togogenome.org/gene/10090:Or6aa1 ^@ http://purl.uniprot.org/uniprot/Q8VFP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5p60 ^@ http://purl.uniprot.org/uniprot/B2RQ97|||http://purl.uniprot.org/uniprot/Q8VFD3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Calu ^@ http://purl.uniprot.org/uniprot/O35887 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CREC family.|||Endoplasmic reticulum membrane|||Golgi apparatus|||Interacts with GGCX.|||Involved in regulation of vitamin K-dependent carboxylation of multiple N-terminal glutamate residues. Seems to inhibit gamma-carboxylase GGCX. Binds 7 calcium ions with a low affinity (By similarity).|||Melanosome|||Sarcoplasmic reticulum lumen|||Secreted http://togogenome.org/gene/10090:Onecut1 ^@ http://purl.uniprot.org/uniprot/O08755 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CUT homeobox family.|||Binds DNA as a monomer.|||Nucleus|||Transcriptional activator. Binds the consensus sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR. Important for liver genes transcription. Stimulates the expression of Onecut3 in the developing endoderm. http://togogenome.org/gene/10090:Vmn1r216 ^@ http://purl.uniprot.org/uniprot/Q8R257 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Notch3 ^@ http://purl.uniprot.org/uniprot/Q61982 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOTCH family.|||CNS development.|||Cell membrane|||Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity). May play a role during CNS development.|||Hydroxylated by HIF1AN.|||Interacts with PSMA1 (By similarity). Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with HIF1AN.|||Nucleus|||Phosphorylated.|||Proliferating neuroepithelium.|||Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane.|||The EGF-like domains 10 and 11 are required for binding the ligands JAG1 and DLL1. http://togogenome.org/gene/10090:Pkd1l2 ^@ http://purl.uniprot.org/uniprot/E9Q4D4|||http://purl.uniprot.org/uniprot/Q7TN88 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the polycystin family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May function as an ion-channel regulator. May function as a G-protein-coupled receptor (By similarity).|||May interact via its C-terminus with GNAS and GNAI1.|||Membrane http://togogenome.org/gene/10090:Cldn34a ^@ http://purl.uniprot.org/uniprot/G3UW52 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Atp1b3 ^@ http://purl.uniprot.org/uniprot/P97370|||http://purl.uniprot.org/uniprot/Q544Q7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the X(+)/potassium ATPases subunit beta family.|||Melanosome|||Membrane|||The C-terminal lobe folds into an immunoglobulin-like domain and may mediate cell adhesion properties.|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with catalytic alpha subunit ATP12A.|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane.|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.|||Widely expressed. http://togogenome.org/gene/10090:Eml2 ^@ http://purl.uniprot.org/uniprot/Q7TNG5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat EMAP family.|||Contains a tandem atypical propeller in EMLs (TAPE) domain. The N-terminal beta-propeller is formed by canonical WD repeats; in contrast, the second beta-propeller contains one blade that is formed by discontinuous parts of the polypeptide chain (By similarity).|||Interacts with GRID2 and may also interact with GRID1. Interacts with EML3. Binds unpolymerized tubulins via its WD repeat region.|||Tubulin binding protein that inhibits microtubule nucleation and growth, resulting in shorter microtubules.|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Lrit1 ^@ http://purl.uniprot.org/uniprot/Q8K099 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Homodimer.|||Possible role in phototransduction. http://togogenome.org/gene/10090:Tex13d ^@ http://purl.uniprot.org/uniprot/A0A0G2JGA3 ^@ Similarity ^@ Belongs to the TEX13 family. http://togogenome.org/gene/10090:Anapc10 ^@ http://purl.uniprot.org/uniprot/Q8K2H6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the APC10 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. The C-terminus of APC10 binds to CDC27/APC3 (By similarity). Interacts with PIWIL1; interaction only takes place when PIWIL1 binds piRNA (PubMed:23328397). Interacts with FBXO43; the interaction is direct. http://togogenome.org/gene/10090:Shkbp1 ^@ http://purl.uniprot.org/uniprot/Q6P7W2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KCTD3 family.|||Inhibits CBL-SH3KBP1 complex mediated down-regulation of EGFR signaling by sequestration of SH3KBP1. Binds to SH3KBP1 and prevents its interaction with CBL and inhibits translocation of SH3KBP1 to EGFR containing vesicles upon EGF stimulation (PubMed:21830225).|||Lysosome|||Monomer (By similarity). Interacts with CUL3; interaction is direct and forms a 5:5 heterodecamer (By similarity). Interacts (via PXXXPR motifs) with SH3KBP1 (via SH3 domains) (PubMed:11152963, PubMed:21830225). Directly interacts with cathepsin B/CTSB (By similarity). http://togogenome.org/gene/10090:Tomm70a ^@ http://purl.uniprot.org/uniprot/Q9CZW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as receptor of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex). Recognizes and mediates the translocation of mitochondrial preproteins from the cytosol into the mitochondria in a chaperone dependent manner (By similarity). Mediates TBK1 and IRF3 activation induced by MAVS in response to virus infection and promotes host antiviral responses during virus infection (PubMed:20628368).|||Belongs to the Tom70 family.|||Expressed in the base region of the oxyntic and pyloric mucosae.|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70) (By similarity). Interacts with CAPN8 (PubMed:16476741). Interacts with TRADD, TRAF6 and STING. Interacts with MAVS. Interacts with HSPA8 and HSP90AA1; both interactions are required for preprotein mitochondrial import. The interaction with HSP90AA1 is direct and mediates the association of TOMM70 with IRF3 and TBK1 (By similarity).|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Sema4d ^@ http://purl.uniprot.org/uniprot/O09126 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell membrane|||Cell surface receptor for PLXNB1 and PLXNB2 that plays an important role in cell-cell signaling (By similarity). Regulates GABAergic synapse development (PubMed:23699507, PubMed:29981480). Promotes the development of inhibitory synapses in a PLXNB1-dependent manner (PubMed:23699507, PubMed:29981480). Modulates the complexity and arborization of developing neurites in hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 mediates activation of RHOA (By similarity). Promotes the migration of cerebellar granule cells (PubMed:17554007). Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro) (By similarity). Induces endothelial cell migration through the activation of PTK2B/PYK2, SRC, and the phosphatidylinositol 3-kinase-AKT pathway (By similarity).|||Homodimer (By similarity). Interacts with PLXNB1 (By similarity). Interacts with PLXNB2 (PubMed:17554007).|||Strongly expressed in lymphoid tissues, especially in the thymus, as well as in the nervous tissues (PubMed:8969198). Expressed in neurons and glia in the developing hippocampus (PubMed:29981480). http://togogenome.org/gene/10090:Zfp91 ^@ http://purl.uniprot.org/uniprot/Q62511 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical E3 ubiquitin-protein ligase that mediates 'Lys-63'-linked ubiquitination of MAP3K14/NIK, leading to stabilize and activate MAP3K14/NIK. It thereby acts as an activator of the non-canonical NF-kappa-B2/NFKB2 pathway. May also play an important role in cell proliferation and/or anti-apoptosis.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Found in all the examined tissues including brain, heart, kidney, lung, liver, spleen, thymus, skeletal muscle, ovary and testis.|||In contrast to other E3 ubiquitin-protein ligase, does not contain any domain (RING-type zinc finger or HECT domain) known to mediate E3 ligase activity.|||Interacts with MAP3K14/NIK.|||Nucleus http://togogenome.org/gene/10090:Hes2 ^@ http://purl.uniprot.org/uniprot/O54792 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).|||Nucleus|||The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.|||Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.|||Transcriptional repressor of genes that require a bHLH protein for their transcription. http://togogenome.org/gene/10090:Dmrtc1c1 ^@ http://purl.uniprot.org/uniprot/Q14AJ8|||http://purl.uniprot.org/uniprot/Q9D410 ^@ Similarity ^@ Belongs to the DMRT family. http://togogenome.org/gene/10090:Ankrd28 ^@ http://purl.uniprot.org/uniprot/Q505D1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP1C and HNRPK. Interacts with PPP6C, PPP6R1 and PPP6R3 (By similarity).|||Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates. Involved in the PP6-mediated dephosphorylation of NFKBIE opposing its degradation in response to TNF-alpha. Selectively inhibits the phosphatase activity of PPP1C. Targets PPP1C to modulate HNRPK phosphorylation (By similarity).|||Widely expressed (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Akain1 ^@ http://purl.uniprot.org/uniprot/G3UWD5 ^@ Domain|||Function|||Subunit|||Tissue Specificity ^@ Binds cAMP-dependent protein kinase (PKA). Interacts specifically with RII-regulatory subunits of PKA (PRKAR2A and PRKAR2B).|||Preferentially expressed in the neural tissues.|||Protein kinase A (PKA)-binding protein. Binds to type II regulatory subunits of protein kinase A (PKA) and may block the A-kinase anchoring protein (AKAP)-mediated subcellular localization of PKA.|||The RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer. http://togogenome.org/gene/10090:Tmem104 ^@ http://purl.uniprot.org/uniprot/Q3TB48 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM104 family.|||Membrane http://togogenome.org/gene/10090:Glra1 ^@ http://purl.uniprot.org/uniprot/Q5NCT9|||http://purl.uniprot.org/uniprot/Q64018 ^@ Activity Regulation|||Caution|||Disease Annotation|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 sub-subfamily.|||Cell membrane|||Defects in Glra1 are the cause of the spasmodic (spd) phenotype, a mouse mutant which resembles the human neurological disease, hyperekplexia (or startle disease (STHE)) (PubMed:7920629). Defects in Glra1 are the cause of the lethal oscillator (spd-ot) phenotype. Mutant mice display a fine motor tremor and muscle spasms that begin at 2 weeks of age and progressively worsen, resulting in death by 3 weeks of age (PubMed:7874121). Heterozygous mice show an increased acoustic startle response (PubMed:9145798). Neurons from homozygous oscillator mice have dramatically reduced amplitude and frequency of glycinergic inhibitory postsynaptic currents (PubMed:16672662). The oscillator phenotype is due to the complete absence of Glra1 protein (PubMed:9145798).|||Detected in spinal cord neurons (PubMed:9145798, PubMed:17114051, PubMed:24801766). Detected in brain stem neurons (PubMed:16672662, PubMed:24801766). Detected at lower levels in hippocampus and cerebellum (PubMed:24801766). Detected in the inner plexiform layer of the retina (at protein level) (PubMed:12975813).|||Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:16672662, PubMed:17114051, PubMed:24801766). Channel opening is also triggered by taurine and beta-alanine (By similarity). Channel characteristics depend on the subunit composition; heteropentameric channels are activated by lower glycine levels and display faster desensitization (By similarity). Plays an important role in the down-regulation of neuronal excitability (PubMed:9145798). Contributes to the generation of inhibitory postsynaptic currents (PubMed:16672662, PubMed:17114051, PubMed:24801766). Channel activity is potentiated by ethanol. Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (PubMed:24801766).|||Homopentamer (in vitro). Interacts with GLRB to form heteropentameric channels; this is probably the predominant form in vivo. Heteropentamer composed of two GLRA1 and three GLRB. Heteropentamer composed of three GLRA1 and two GLRB. Both homopentamers and heteropentamers form functional ion channels, but their characteristics are subtly different. Interacts with GLRB (By similarity).|||Inhibited by strychnine. Inhibited by picrotoxin (PubMed:16672662). Channel activity is enhanced by 5 uM Zn(2+) and inhibited by 100 uM Zn(2+) (PubMed:17114051).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Perikaryon|||Postsynaptic cell membrane|||Synapse|||Synaptic cell membrane|||The alpha subunit binds strychnine.|||The channel pore is formed by pentameric assembly of the second transmembrane domain from all five subunits. Channel opening is effected by an outward rotation of the transmembrane domains that increases the diameter of the pore.|||dendrite http://togogenome.org/gene/10090:Eef2k ^@ http://purl.uniprot.org/uniprot/O08796|||http://purl.uniprot.org/uniprot/Q7TPC7|||http://purl.uniprot.org/uniprot/Q8BNP6|||http://purl.uniprot.org/uniprot/Q8CEC8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Autophosphorylated at multiple residues, Thr-347 being the major site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-397 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-77 resulting in improved protein stability, higher EE2F phosphorylated and subsequently reduced rate of protein synthesis. Phosphorylation by other kinases such as CDK1 and MAPK13 at Ser-358 or RPS6KA1 and RPS6KB1 at Ser-365 instead decrease EEF2K activity and promote protein synthesis (By similarity).|||Belongs to the protein kinase superfamily. Alpha-type protein kinase family.|||Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (By similarity).|||Monomer or homodimer.|||Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation (PubMed:9144159, PubMed:34815424). Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive (PubMed:9144159, PubMed:34815424). In turn, the rate of protein synthesis is reduced (PubMed:9144159, PubMed:34815424).|||Ubiquitously expressed (PubMed:9144159). Particularly abundant in skeletal muscle and heart (PubMed:9144159).|||Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent. http://togogenome.org/gene/10090:Or1ad8 ^@ http://purl.uniprot.org/uniprot/Q8VGG9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Miga1 ^@ http://purl.uniprot.org/uniprot/B2RRB9|||http://purl.uniprot.org/uniprot/Q4QQM5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitoguardin family.|||Homodimer and heterodimer; forms heterodimers with MIGA2. Interacts with PLD6/MitoPLD.|||Mitochondrial fragmentation: mitochondria become round and show loss of cristae (PubMed:26711011). Female mice show decreased quality of oocytes (PubMed:26716412). Mice lacking both Miga1 and Miga2 show strongly reduced quality of oocytes and are subfertile (PubMed:26716412).|||Mitochondrion outer membrane|||Regulator of mitochondrial fusion (PubMed:26711011). Acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD (By similarity). http://togogenome.org/gene/10090:Rpl13a ^@ http://purl.uniprot.org/uniprot/P19253|||http://purl.uniprot.org/uniprot/Q5M9M0 ^@ Function|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions (PubMed:36517592). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma activation and subsequent phosphorylation dissociates from the ribosome and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (By similarity). In the GAIT complex interacts with m7G cap-bound eIF4G at or near the eIF3-binding site and blocks the recruitment of the 43S ribosomal complex (By similarity). Involved in methylation of rRNA (By similarity).|||Belongs to the universal ribosomal protein uL13 family.|||Citrullinated by PADI4.|||Component of the 60S ribosome (PubMed:36517592). Component of the GAIT complex (By similarity). Interacts with EIF4G1 (By similarity).|||Cytoplasm|||Phosphorylation at Ser-77 upon interferon-gamma treatment in macrophages involves a DAPK1-DAPK3 kinase cascade and is causing release from the ribosome, association with the GAIT complex and subsequent involvement in transcript-selective translation inhibition.|||The antigenic allele of P198 differs from the normal allele by a single mutation. The TUM- mutation P198 generates a new epitope recognized by syngeneic T-cells. http://togogenome.org/gene/10090:Surf6 ^@ http://purl.uniprot.org/uniprot/P70279|||http://purl.uniprot.org/uniprot/Q3V1X4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SURF6 family.|||Binds to both DNA and RNA in vitro, with a stronger binding capacity for RNA. May represent a nucleolar constitutive protein involved in ribosomal biosynthesis or assembly.|||Citrullinated by PADI4.|||Expressed in all tissues tested, including heart, brain, spleen, lung, liver, muscle, kidney and testis.|||nucleoplasm http://togogenome.org/gene/10090:Ptpn9 ^@ http://purl.uniprot.org/uniprot/O35239 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class 3 subfamily.|||Cytoplasm|||Protein-tyrosine phosphatase that could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus. http://togogenome.org/gene/10090:Fbxo8 ^@ http://purl.uniprot.org/uniprot/Q9QZN3 ^@ Function|||Tissue Specificity ^@ High expression in brain, heart, kidney, liver, lung, skeletal muscle, testis, and day-7 embryos.|||May promote guanine-nucleotide exchange on an ARF. Promotes the activation of ARF through replacement of GDP with GTP (Potential). http://togogenome.org/gene/10090:Alkbh6 ^@ http://purl.uniprot.org/uniprot/Q8K2U2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||Interacts with VCPKMT.|||Nucleus|||Probable dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron. http://togogenome.org/gene/10090:Zfp58 ^@ http://purl.uniprot.org/uniprot/P16372 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Contaminating sequence. Potential poly-A sequence.|||Expressed in liver, testis and, at considerably lower levels, in brain, spleen and heart.|||Expression increases upon differentiation and is not related to the cell cycle.|||May have a role during differentiation processes.|||Nucleus http://togogenome.org/gene/10090:1500009L16Rik ^@ http://purl.uniprot.org/uniprot/P0C913 ^@ Similarity ^@ Belongs to the OCC1 family. http://togogenome.org/gene/10090:Stk40 ^@ http://purl.uniprot.org/uniprot/Q7TNL3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||May be a negative regulator of NF-kappa-B and p53-mediated gene transcription.|||Nucleus http://togogenome.org/gene/10090:Ampd1 ^@ http://purl.uniprot.org/uniprot/Q3V1D3 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ AMP deaminase plays a critical role in energy metabolism.|||Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.|||Binds 1 zinc ion per subunit.|||Homotetramer. http://togogenome.org/gene/10090:Arhgap29 ^@ http://purl.uniprot.org/uniprot/Q8CGF1 ^@ Developmental Stage|||Function|||Subunit ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has strong activity toward RHOA, and weaker activity toward RAC1 and CDC42. May act as a specific effector of RAP2A to regulate Rho (By similarity). In concert with RASIP1, suppresses RhoA signaling and dampens ROCK and MYH9 activities in endothelial cells and plays an essential role in blood vessel tubulogenesis.|||In embryos, present in the endothelial cells of the paired aortae during vasculogenesis (at protein level).|||Interacts with PTPN13/PTPL1. Interacts with RAP2A via its coiled coil domain (By similarity). Interacts with RASIP1. http://togogenome.org/gene/10090:Scand1 ^@ http://purl.uniprot.org/uniprot/Q2M4I6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:H2al1f ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:Klf7 ^@ http://purl.uniprot.org/uniprot/Q99JB0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Deficient mice die within the first 3 days of life, showing little or no milk in the stomachs, hypopnea, cyanosis, olfactory bulb hypoplasia, axon outgrowth defects in the olfactory and optic nerves, defects of axon growth in the brain and reduced dendritic branching in the hippocampus.|||Expression starts at 8.5 dpc in the trigeminal ganglion, the VII-VIII neural crest complex, and the subventricular neuroepithelium of both forebrain and hindbrain regions. At 11.5 dpc, expression is detected in the neural crest-derived sensory nervous system and, at 15.5 dpc, in the brain, spinal cord, retinal neuroepithelium and the inferior XI/X complex (PubMed:11336497, PubMed:11245580). In postnatal and adult animals, expression is confined to the cerebellum and dorsal root ganglia (PubMed:11336497). Expressed in the cornea epithelium at both 18.5 dpc and early postnatal (P5) but not at P50, when the corneal epithelium is fully differentiated (PubMed:28916725).|||Interacts with FBXO38.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF7, the motif is inactive.|||The acidic N-terminal part may favor interaction with the basic domain of transcription factors.|||Transcriptional factor (PubMed:11245580). Plays a critical role in neuronal morphogenesis (PubMed:11336497, PubMed:15964824). Represses the corneal epithelium differentiation (By similarity). Acts also as a metabolic regulator, by modulating insulin sensitivity in pancreatic beta cells and skeletal muscle cells. Inhibits transcriptional inducers of adipogenesis and has a repressive role in the expression of several adipokines, including leptin (By similarity).|||Widely expressed (PubMed:11336497). Detected in the cornea epithelium (at protein level) (PubMed:28916725). http://togogenome.org/gene/10090:Scn2a ^@ http://purl.uniprot.org/uniprot/A0A5H1ZRM8|||http://purl.uniprot.org/uniprot/B1AWN6 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.2/SCN2A subfamily.|||Cell membrane|||Conditional knockout mice deficient in brain are morphologically and organogenically indistinguishable from their heterozygous littermates. They die perinatally with severe hypoxia and massive neuronal apoptosis, notably in the brainstem. Sodium channel currents recorded from cultured neurons of knockout mice are sharply attenuated.|||Expressed in brain (at protein level) (PubMed:10827969, PubMed:11166117). Detected in hippocampus, cortex and brain stem (PubMed:10827969).|||Heterooligomer of a large alpha subunit and a smaller beta subunit. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Interacts with NEDD4L. Interacts with CALM.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:10827969, PubMed:11166117, PubMed:28137877). Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory (PubMed:29867081).|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Membrane|||Sumoylated at Lys-38. Sumoylation is induced by hypoxia, increases voltage-gated sodium current and mediates the early response to acute hypoxia in neurons. Sumoylated SCN2A is located at the cell membrane.|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Lypd2 ^@ http://purl.uniprot.org/uniprot/Q9DD23 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Fahd1 ^@ http://purl.uniprot.org/uniprot/Q8R0F8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAH family.|||Homodimer.|||Mitochondrion|||No visible phenotype. Elevated oxaloacetate levels.|||Probable mitochondrial acylpyruvase which is able to hydrolyze acetylpyruvate and fumarylpyruvate in vitro (By similarity). Also has oxaloacetate decarboxylase activity (PubMed:25575590).|||Ubiquitous with higher expression in the liver and the kidney (at protein level).|||cytosol http://togogenome.org/gene/10090:Foxb1 ^@ http://purl.uniprot.org/uniprot/Q64732 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in oligodendrocyte-generating regions of the embryonic hindbrain.|||Expressed widespread in the early developing ventricular zone of the neural tube and later restricted to areas of the spinal cord, hindbrain, thalamus and hypothalamus (PubMed:28725186, PubMed:27292133, PubMed:15654859, PubMed:11170346). Expressed in epithelial cells of developing and adult mammary glands (PubMed:11170346).|||Mutants suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Mutants show no deficits in hippocampal-dependent tasks as contextual fear conditioning and social transmission of food preference. They have a highly specific memory deficit, restricted to the performance of spatial working memory tasks with no impairment of spatial reference memory (PubMed:15654859). Female mutants have lactation defects with mammary glands with incomplete lobuloavelor development and morphological defects in the inferior colliculi of the midbrain (PubMed:11170346).|||Nucleus|||Transcription factor expressed by neural progenitor cells in specific regions of the embryonic neuroepithelium (PubMed:28725186, PubMed:15654859). Essential for the mammillary nuclei maintenance (PubMed:15654859). Negatively regulates the proliferation of oligodendrocyte progenitors and promotes oligodendrocyte maturation (PubMed:28725186). Also expressed in mammary glands, plays a role in lactation, controls development of mammary glands and the inferior colliculi of the midbrain in the central nervous system that regulates the milk-ejection reflex (PubMed:11170346). http://togogenome.org/gene/10090:Lars ^@ http://purl.uniprot.org/uniprot/Q7TSZ3|||http://purl.uniprot.org/uniprot/Q8BMJ2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ 5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole inhibits LARS1 by forming a covalent adduct with the 3' adenosine of tRNA(Leu) at the editing site, thus locking the enzyme in an inactive conformation.|||Belongs to the class-I aminoacyl-tRNA synthetase family.|||Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs.|||Cytoplasm http://togogenome.org/gene/10090:Gsdmc3 ^@ http://purl.uniprot.org/uniprot/Q8CB12 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage by CASP8 relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-C3, N-terminal) that initiates pyroptosis.|||Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.|||Pore-forming protein that causes membrane permeabilization and pyroptosis. Produced by the cleavage of gasdermin-D by caspase CASP8 in response to death signals (By similarity). After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (By similarity).|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C3, N-terminal) following cleavage by caspase CASP8 (By similarity).|||This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C3, N-terminal) binds to membranes and forms pores, triggering pyroptosis.|||cytosol http://togogenome.org/gene/10090:Cfb ^@ http://purl.uniprot.org/uniprot/B8JJM5|||http://purl.uniprot.org/uniprot/B8JJM6|||http://purl.uniprot.org/uniprot/Q3UEG8 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Mrpl36 ^@ http://purl.uniprot.org/uniprot/Q99N90 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL36 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Neurog3 ^@ http://purl.uniprot.org/uniprot/P70661 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional regulator. Together with NKX2-2, initiates transcriptional activation of NEUROD1. Involved in neurogenesis. Also required for the specification of a common precursor of the 4 pancreatic endocrine cell types.|||Efficient DNA binding requires dimerization with another bHLH protein. Interacts with ATOH8.|||Nucleus http://togogenome.org/gene/10090:Aoah ^@ http://purl.uniprot.org/uniprot/O35298 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals develop significant and prolonged hepatosplenomegaly in response to bacterial lipopolysaccharide (LPS) challenge (PubMed:17322564). Both liver and spleen show increased accumulation of leukocytes (PubMed:17322564). Significantly reduced deacylation of LPS in liver and spleen, in peritoneal macrophages, and in bone marrow-derived dendritic cells (PubMed:12810692, PubMed:17322564, PubMed:18779055). Increased lung injury, delayed neutrophil clearance, and prolonged recovery time in response to intranasal LPS administration (PubMed:28622363). Alveolar macrophages show persistent activation and cytokine levels in lung remain elevated 4-7 days after LPS administration (PubMed:28622363). Impaired response to a second infection challenge, with reduced production of the pro-inflammatory chemokines CCL5/RANTES, TNF and IL6 by peritoneal macrophages and reduced survival rates, indicating a prolonged state of immune tolerance (PubMed:18779055). This immune tolerant state can perisist for two months or longer (PubMed:18779055).|||Binds 3 Ca(2+) ions per subunit. The calcium ions probably have a structural role.|||Cleaved into a large and a small subunit.|||Cytoplasmic vesicle|||Detected in peritoneal macrophages (at protein level) (PubMed:17322564, PubMed:28622363). Strongly expressed in kidney cortex, where it may be produced by proximal tubule cells (PubMed:15155618). In liver, expressed at high levels in Kupffer cells (PubMed:17322564). Expressed by dendritic cells (PubMed:12810692). Detected at low levels in alveolar macrophages (PubMed:28622363).|||Heterodimer of the large and small subunits; disulfide-linked.|||Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS) (PubMed:12810692, PubMed:15155618, PubMed:17322564, PubMed:19860560). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses (PubMed:17322564, PubMed:19860560, PubMed:28622363). In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria (PubMed:18779055).|||Secreted|||Strongly up-regulated in alveolar macrophages in response to bacterial lipopolysaccharides (LPS).|||The small subunit is N-glycosylated. http://togogenome.org/gene/10090:Adam18 ^@ http://purl.uniprot.org/uniprot/Q9R157 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ A tripeptide motif (ECD) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.|||Adult levels are reached by day 16 after birth.|||Expressed specifically in testis.|||Membrane|||Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein.|||The prodomain and the metalloprotease-like domain are cleaved during the epididymal maturation of the spermatozoa. http://togogenome.org/gene/10090:Fcho2 ^@ http://purl.uniprot.org/uniprot/Q3UQN2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FCHO family.|||Functions in an early step of clathrin-mediated endocytosis. Has both a membrane binding/bending activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a lipid-binding activity with a preference for membranes enriched in phosphatidylserine and phosphoinositides (Pi(4,5) biphosphate) like the plasma membrane. Its membrane-bending activity might be important for the subsequent action of clathrin and adaptors in the formation of clathrin-coated vesicles. Involved in adaptor protein complex AP-2-dependent endocytosis of the transferrin receptor, it also functions in the AP-2-independent endocytosis of the LDL receptor.|||Homodimer; disulfide-linked (By similarity). May form homotetramer. Interacts with AP2A1. Interacts with EPS15, EPS15R, ITSN1 and ITSN2; recruit those scaffolding proteins which in turn may interact with the adaptor protein complex AP-2 at the plasma membrane. Interacts with DAB2 (via DPF motifs); mediates LDL receptor/LDLR endocytosis.|||Ubiquitinated. Mainly undergoes monoubiquitination but also polyubiquitination.|||Ubiquitously expressed (at protein level).|||clathrin-coated pit http://togogenome.org/gene/10090:Pabpc6 ^@ http://purl.uniprot.org/uniprot/Q9D4E6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the polyadenylate-binding protein type-1 family.|||Binds the poly(A) tail of mRNA.|||Cytoplasm http://togogenome.org/gene/10090:Slf1 ^@ http://purl.uniprot.org/uniprot/Q8R3P9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ BRCT domains are necessary for its targeting to ionizing radiation-induced nuclear foci (PubMed:22036607).|||Cytoplasm|||Expressed in the developing embryo (PubMed:15632077).|||Interacts (via BRCT domains) with RAD18 (via C-terminus and phosphorylated form); this interaction is required for efficient repair of UV-induced DNA damage (PubMed:15632077, PubMed:22036607). Interacts (via N-terminus) with SLF2; this interaction links RAD18 to the SMC5-SMC6 complex. Interacts (via BRCT domains) with RAD18; this interaction occurs in a SLF2-independent manner. Interacts with SMC6.|||Mice develop normally, display no pathological abnormalities and are fertile (PubMed:15632077).|||Nucleus|||Plays a role in the DNA damage response (DDR) pathway by regulating postreplication repair of UV-damaged DNA and genomic stability maintenance. The SLF1-SLF2 complex acts to link RAD18 with the SMC5-SMC6 complex at replication-coupled interstrand cross-links (ICL) and DNA double-strand breaks (DSBs) sites on chromatin during DNA repair in response to stalled replication forks. Promotes the recruitment of SLF2 and the SMC5-SMC6 complex to DNA lesions.|||Widely expressed (PubMed:15632077). Expressed in testis (PubMed:15632077). Expressed in spermatocytes (PubMed:15632077).|||centrosome http://togogenome.org/gene/10090:Krtap13-1 ^@ http://purl.uniprot.org/uniprot/Q8K198 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Socs1 ^@ http://purl.uniprot.org/uniprot/O35716 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SOCS1 family.|||By a subset of cytokines including those belonging to the interferon, interleukin and colony-stimulating factor families.|||Cytoplasmic vesicle|||Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF) (PubMed:9202125, PubMed:10064597, PubMed:15169905, PubMed:15522878). Downregulates cytokine signaling by inhibiting the JAK/STAT signaling pathway. Acts by binding to JAK proteins and to IFNGR1 and inhibiting their kinase activity (PubMed:9202125, PubMed:10064597, PubMed:15522878). In vitro, suppresses Tec protein-tyrosine activity (By similarity). Regulates IFN-gamma (IFNG)-mediated sensory neuron survival. Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).|||High expression in thymus. Lower expression in lung and spleen (PubMed:9202125). Expressed in both Th1 and Th2 cells.|||In the developing brain, expressed at low levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8. In the cortex, expression first observed at 14 dpc uniformly in all cells. Also expressed in the innermost layers of the developing retina. Levels of expression remain unchanged from P8 until adulthood. In the peripheral nervous system, high levels found in virtually all neurons of the dorsal root ganglion.|||Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including JAK family kinases, TEC, KIT, GRB2 and VAV. Binding to JAKs is mediated through the KIR and SH2 domain to a phosphorylated tyrosine residue within the JAK JH1 domain. Binds the SH3 domain of GRB2 via diproline determinants in the N-terminus, and the N-terminal regulatory domain of VAV. Interacts with the Elongin BC complex (ELOB and ELOC). Component of an ECS CBC(SOCS1) E3 ubiquitin-protein ligase complex which contains Elongin BC, CUL5, RBX1 and SOCS1. Interacts (via SH2 domain and SOCS box) with TRIM8. Interacts with CUL2. Interacts with AXL and FGFR3 (By similarity). Interacts with INSR. Interacts with TRIM8 (By similarity). Interacts with DCUN1D1 (By similarity). Interacts with IFNGR1 (PubMed:15522878).|||Mice exhibit lymphocyte deficiency and degeneration of the liver parenchyma. Animals die within 3 weeks of age. Mutants show a much higher frequency of CD8 single positive thymocytes (PubMed:24880459).|||Nucleus|||The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV] and is part of the SOCS box. http://togogenome.org/gene/10090:Unc119b ^@ http://purl.uniprot.org/uniprot/Q8C4B4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that capture N-terminally myristoylated target peptides. Phe residues within the hydrophobic beta sandwich are required for myristate binding (By similarity).|||Belongs to the PDE6D/unc-119 family.|||Found in a complex with ARL3, RP2 and UNC119B; RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119B. Interacts with NPHP3 (when myristoylated). Interacts with CYS1 (when myristoylated). Interacts with MACIR; interaction only takes place when UNC119B is not liganded with myristoylated proteins (By similarity).|||Myristoyl-binding protein that acts as a cargo adapter: specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated NPHP3 and plays a key role in localization of NPHP3 to the primary cilium membrane. Does not bind all myristoylated proteins. Probably plays a role in trafficking proteins in photoreceptor cells (By similarity).|||cilium http://togogenome.org/gene/10090:Vmn1r113 ^@ http://purl.uniprot.org/uniprot/G3UWI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sct ^@ http://purl.uniprot.org/uniprot/A0A1B0GS37|||http://purl.uniprot.org/uniprot/Q08535|||http://purl.uniprot.org/uniprot/Q3UKU8|||http://purl.uniprot.org/uniprot/Q80ZS9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glucagon family.|||Highly expressed in the intestine (PubMed:18534766). Also expressed in the hippocampus, cerebellum and the brain stem in adult mouse brain (PubMed:18534766). In the hippocampus, expressed in the dentate gyrus, the hilus and the molecular layer (PubMed:18534766).|||Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:20578263, PubMed:20739612, PubMed:20927047, PubMed:30449620). Exerts its biological effects by binding to secretin receptor (SCTR), a G-protein coupled receptor expressed in the basolateral domain of several cells (PubMed:30449620). Acts as a key gastrointestinal hormone by regulating the pH of the duodenal content (PubMed:20578263). Secreted by S cells of the duodenum in the crypts of Lieberkuehn and regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas (PubMed:20578263). Production of bicarbonate is essential to neutralize the pH and ensure no damage is done to the small intestine by the gastric acid (PubMed:20578263). In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation (PubMed:30449620). Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation (PubMed:30449620). Also able to stimulate lipolysis in white adipocytes (PubMed:24273196). Also plays an important role in cellular osmoregulation: released into the systemic circulation in response to hyperosmolality and acts at different levels in the hypothalamus, pituitary and kidney to regulate water homeostasis (PubMed:20739612). Also plays a role in the central nervous system, possibly by acting as a neuropeptide hormone: required for hippocampal synaptic function and neural progenitor cells maintenance (PubMed:18534766, PubMed:21159798).|||Mice are viable and fertile (PubMed:18534766). Mice however display impairment in synaptic plasticity in the CA1 area of the hippocampus (PubMed:18534766). Mice exhibit decreased neural progenitor cells in the subgranular zone of the dentate gyrus during the early postnatal period, leading to decreased volume of dentate gyrus, reduced long-term potentiation and impaired spatial learning ability in adults (PubMed:21159798).|||Secreted http://togogenome.org/gene/10090:Snapc1 ^@ http://purl.uniprot.org/uniprot/Q8K0S9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC1 interacts with SNAPC3, SNAPC4 and TBP (By similarity).|||Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box (By similarity). http://togogenome.org/gene/10090:Rpusd4 ^@ http://purl.uniprot.org/uniprot/Q9CWX4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pseudouridine synthase RluA family.|||Catalyzes uridine to pseudouridine isomerization (pseudouridylation) of different mitochondrial RNA substrates. Acts on position 1397 in 16S mitochondrial ribosomal RNA (16S mt-rRNA). This modification is required for the assembly of 16S mt-rRNA into a functional mitochondrial ribosome. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA, controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation. Acts on position 39 in mitochondrial tRNA(Phe). Also catalyzes pseudouridylation of mRNAs in nucleus: acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions. Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3'-end processing.|||Cytoplasm|||Interacts with 16S mt-rRNA, mt-tRNA(Phe) and mt-tRNA(Met). Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA.|||Mitochondrion matrix|||Nucleus http://togogenome.org/gene/10090:Ap3s1 ^@ http://purl.uniprot.org/uniprot/A0A286YDU3|||http://purl.uniprot.org/uniprot/Q3U8S0|||http://purl.uniprot.org/uniprot/Q9DCR2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (By similarity). AP-3 associates with the BLOC-1 complex. Interacts with AGAP1.|||Belongs to the adaptor complexes small subunit family.|||Cytoplasmic vesicle membrane|||Golgi apparatus|||Membrane|||Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. http://togogenome.org/gene/10090:Rarres2 ^@ http://purl.uniprot.org/uniprot/A0A0N4SVV4|||http://purl.uniprot.org/uniprot/Q9DD06 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Acts also as a ligand for CMKLR2. Can also bind to C-C chemokine receptor-like 2 (CCRL2), but with a lower affinity than it does to CMKLR1 or CMKLR2. Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a pro-inflammatory adipokine, causing an increase in secretion of pro-inflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Exhibits an antimicrobial function in the skin.|||Expressed in the differentiated adipocytes (at protein level). Abundantly expressed in the liver, adipose tissue including visceral, epididymal, and brown adipose tissue.|||Secreted|||Secreted in an inactive precursor form, prochemerin, which is proteolytically processed by a variety of extracellular proteases to generate forms with differing levels of bioactivity. For example, the removal of six amino acids results in chemerin-156, which exhibits the highest activity, while removal of seven amino acids results in chemerin-155 which has slightly less activity. Some proteases are able to cleave at more than one site and chemerin forms may be sequentially processed by different enzymes to modulate activity levels. The coordinated expression and activity of chemerin-modifying enzymes is essential for regulating its bioactivation, inactivation and, consequently, biological function. Cathepsin G cleaves seven C-terminal amino acids from prochemerin (chemerin-155), elastase is able to cleave six (chemerin-156), eight (chemerin-154) or eleven (chemerin-151), plasmin cleaves five amino acids (chemerin-157), and tryptase cleaves five (chemerin-157) or eight (chemerin-154). Multiple cleavages might be required to fully activate chemerin, with an initial tryptase cleavage resulting in chemerin with low activity (chemerin-157), and a second cleavage by carboxypeptidase N or B producing highly active chemerin (chemerin-156) (By similarity).|||Strongly induced during adipocyte differentiation. http://togogenome.org/gene/10090:Tbc1d8b ^@ http://purl.uniprot.org/uniprot/A3KGB4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts (via domain Rab-GAP TBC) with RAB11B (in GTP-bound form).|||Involved in vesicular recycling, probably as a RAB11B GTPase-activating protein.|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.|||cytosol http://togogenome.org/gene/10090:Tmem150b ^@ http://purl.uniprot.org/uniprot/Q8R218 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DRAM/TMEM150 family.|||Cell membrane|||Endosome membrane|||Modulator of macroautophagy that causes accumulation of autophagosomes under basal conditions and enhances autophagic flux (By similarity). Represses cell death and promotes long-term clonogenic survival of cells grown in the absence of glucose in a macroautophagy-independent manner (By similarity). May have some role in extracellular matrix engulfment or growth factor receptor recycling, both of which can modulate cell survival (By similarity).|||autophagosome membrane http://togogenome.org/gene/10090:Bag3 ^@ http://purl.uniprot.org/uniprot/Q9JLV1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds to the ATPase domain of HSP70/HSC70 chaperones. Interacts with BCL2. Interacts with phospholipase C-gamma proteins. Interacts with DNAJB6. Interacts (via BAG domain) with HSF1; this interaction occurs in normal and heat-shocked cells. Interacts with HSPA8 (via NBD), HSPA1A (via NBD) and HSPA1B (via NBD). Interacts (via WW domain 1) with SYNPO2 (via PPPY motif).|||Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70. Has anti-apoptotic activity. Plays a role in the HSF1 nucleocytoplasmic transport.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Zdbf2 ^@ http://purl.uniprot.org/uniprot/Q5SS00 ^@ Caution ^@ Compared to its human ortholog it has lost the N-terminal DBF4-type zinc finger. http://togogenome.org/gene/10090:Il17a ^@ http://purl.uniprot.org/uniprot/Q544E6|||http://purl.uniprot.org/uniprot/Q62386 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-17 family.|||Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (PubMed:18025225, PubMed:19144317, PubMed:26431948). Signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:17911633, PubMed:16200068, PubMed:19144317, PubMed:26431948). Plays an important role in connecting T cell-mediated adaptive immunity and acute inflammatory response to destroy extracellular bacteria and fungi. As a signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites (PubMed:18025225). In airway epithelium, mediates neutrophil chemotaxis via induction of CXCL1 and CXCL5 chemokines (PubMed:18025225, PubMed:27923703). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (PubMed:18157131). Effector cytokine of a subset of gamma-delta T cells that functions as part of an inflammatory circuit downstream IL1B, TLR2 and IL23A-IL12B to promote neutrophil recruitment for efficient bacterial clearance (PubMed:17372004, PubMed:20364087, PubMed:28709803). Effector cytokine of innate immune cells including invariant natural killer cell (iNKT) and group 3 innate lymphoid cells that mediate initial neutrophilic inflammation (PubMed:17470641, PubMed:23255360). Involved in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Upon acute injury, has a direct role in epithelial barrier formation by regulating OCLN localization and tight junction biogenesis (PubMed:26431948). As part of the mucosal immune response induced by commensal bacteria, enhances host's ability to resist pathogenic bacterial and fungal infections by promoting neutrophil recruitment and antimicrobial peptides release (PubMed:28709803). In synergy with IL17F, mediates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (PubMed:19144317). Involved in antiviral host defense through various mechanisms (PubMed:21946434, PubMed:26735852, PubMed:27795421). Enhances immunity against West Nile virus by promoting T cell cytotoxicity (PubMed:27795421). May play a beneficial role in influenza A virus (H5N1) infection by enhancing B cell recruitment and immune response in the lung (PubMed:21946434). Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (PubMed:26735852).|||Expressed by Th17 cell lineage (at protein level). The expression pattern reflects the differentiation state, with IL17A-IL17F heterodimers produced at higher levels than IL17A-IL17A and IL17F-IL17F dimers in fully differentiated Th17 cells (PubMed:18025225, PubMed:16990136). Expressed in innate lymphoid cells (at protein level) (PubMed:23255360, PubMed:28709803). Expressed in gamma-delta T cell subsets (at protein level) (PubMed:17372004, PubMed:20364087, PubMed:28709803, PubMed:26431948). Expressed in iNKT cells (at protein level) (PubMed:17470641).|||Homodimer (PubMed:18025225). Forms complexes with IL17RA and IL17RC receptors with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (By similarity). IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex (By similarity). IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer (By similarity). Heterodimer with IL17F (PubMed:18025225). IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (By similarity). IL17RA and IL17RC chains cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (By similarity).|||Induced upon differentiation of CD4-positive T cells toward Th17 effector cells upon antigen receptor binding in the presence of IL6 and TGFB1 (PubMed:16200068, PubMed:16990136, PubMed:18025225). Up-regulated by IL23A-IL12B, IL1B and TNF and inhibited by IFNG and IL4 (PubMed:16200068, PubMed:18025225). Up-regulated by pro-inflammatory cytokines in response to microbes in various immune cells: induced in innate lymphoid cells upon fungal infection, in Vdelta4-positive gamma-delta T cells upon C.mastitidis infection, in Vdelta5-positive gamma-delta T cells upon S.aureus infection and in Vdelta1-positive gamma-delta T cells upon E.coli infection (PubMed:23255360, PubMed:28709803, PubMed:20364087, PubMed:17372004). Induced in gamma-delta T cells in intestinal lamina propria upon acute injury (PubMed:26431948). Induced in KLRB1/NK1.1-negative iNKT cell subset upon CD1D stimulation (PubMed:17470641).|||Mutant mice are born at the expected Mendelian ratio, are fertile, and have no apparent phenotypic abnormalities. They are protected against chronic autoimmune and allergic reactions, as observed in models of spontaneous or induced rheumatoid arthritis, experimental autoimmune encephalomyelitis and chemical allergen-induced contact hypersensitivity (PubMed:19144317). In a model of acute intestinal injury, mutant mice show epithelial disruption, presence of abscesses associated with enhanced bleeding into the mucosal lumen and increased cellular infiltrate into the submucosal layer (PubMed:26431948). Mutant mice show increased susceptibility to West Nile virus infection characterized by deficient virus clearance from brain and spleen (PubMed:27795421). Mutant mice are deficient in clearing influenza A virus (H1N1) pulmonary infection due to increased immune inflammation and lung damage (PubMed:26735852).|||Secreted http://togogenome.org/gene/10090:Hdhd5 ^@ http://purl.uniprot.org/uniprot/Q91WM2 ^@ Similarity ^@ Belongs to the HAD-like hydrolase superfamily. http://togogenome.org/gene/10090:Pkig ^@ http://purl.uniprot.org/uniprot/O70139|||http://purl.uniprot.org/uniprot/Q3TP50 ^@ Function|||Similarity ^@ Belongs to the PKI family.|||Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains. http://togogenome.org/gene/10090:Gabrp ^@ http://purl.uniprot.org/uniprot/Q8QZW7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRP sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone (By similarity).|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and epsilon. A sixth class of subunit: Rho form homomeric GABA receptors that do not appear to coexist with GABA(A) receptor subunits but with GABA(C) receptor subunits. Subunit Pi can also bind this complex (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Abi2 ^@ http://purl.uniprot.org/uniprot/A0A087WRS3|||http://purl.uniprot.org/uniprot/P62484|||http://purl.uniprot.org/uniprot/Q6AXD2|||http://purl.uniprot.org/uniprot/Q6AXH6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ABI family.|||Component of the WAVE complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WASF1/WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1 (By similarity). Interacts (via SH3 domain) with ABL1 and ABL2 (By similarity).|||Detected at 10 dpc in developing brain, and expression is more prominent in the neuroepithelium compared to the surrounding tissue. At 12 dpc expression is enhanced throughout the CNS and is detected along the full length of the spinal chord. At 16 dpc expression remains enhanced in the CNS, and is particularly prominent in the olfactory bulb (PubMed:10995551). Also highly expressed in dorsal root ganglia (PubMed:10995551). At 18.5 dpc is prominently expressed in the marginal zone of the cortex, an area rich in neuronal and glial cell projections (at protein level) (PubMed:15572692). Detected at 16.5 dpc in ocular lens, specifically localized where the tips of migrating secondary fibers forms adherens junctions with anterior epithelial cells (at protein level) (PubMed:15572692).|||Expresses in embryonic and adult brain. In adult brain prominently expressed in the neocortex, hippocampus and dentate gyrus.|||Knockout mice are born at the expected Mendelian rate. Mutant mice have grossly distorted lenses due to defective orientation and migration of secondary lens fibers associated with impaired anterior and posterior sutures formation. Mice exhibit neuroanatomical abnormalities characterized by defective dendritic spine morphology and misoriented cortical and hippocampal neurons, causing profound deficits in learning and memory.|||Phosphorylated by ABL1.|||Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion. Functions as a component of the WAVE complex, which activates actin nucleating machinery Arp2/3 to drive lamellipodia formation (By similarity). Acts as regulator and substrate of nonreceptor tyrosine kinases ABL1 and ABL2 involved in processes linked to cell growth and differentiation. Positively regulates ABL1-mediated phosphorylation of ENAH, which is required for proper polymerization of nucleated actin filaments at the leading edge (By similarity). Contributes to the regulation of actin assembly at the tips of neuron projections. In particular, controls dendritic spine morphogenesis and may promote dendritic spine specification toward large mushroom-type spines known as repositories of memory in the brain (PubMed:15572692). In hippocampal neurons, may mediate actin-dependent BDNF-NTRK2 early endocytic trafficking that triggers dendrite outgrowth (PubMed:27605705). Participates in ocular lens morphogenesis, likely by regulating lamellipodia-driven adherens junction formation at the epithelial cell-secondary lens fiber interface (PubMed:15572692). Also required for nascent adherens junction assembly in epithelial cells (By similarity).|||The SH3 domain is critical for binding to ABL1 and ABL2.|||adherens junction|||cytoskeleton|||dendritic spine|||filopodium|||lamellipodium http://togogenome.org/gene/10090:Cdc40 ^@ http://purl.uniprot.org/uniprot/Q9DC48 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the catalytic spliceosome C complexes. Component of the postcatalytic spliceosome P complex (By similarity). Interacts with PPIL1; this interaction leads to CDC40 isomerization (By similarity).|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the activated spliceosome (By similarity). Plays an important role in embryonic brain development; this function does not require proline peptide bond isomerization (PubMed:33220177).|||Undergoes isomerization of the peptide bond between Gly-94 and Pro-95. The reaction is catalyzed by PPIL1. http://togogenome.org/gene/10090:Mob3a ^@ http://purl.uniprot.org/uniprot/Q8BSU7 ^@ Function|||Similarity ^@ Belongs to the MOB1/phocein family.|||May regulate the activity of kinases. http://togogenome.org/gene/10090:Ahcyl1 ^@ http://purl.uniprot.org/uniprot/Q80SW1 ^@ Caution|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the adenosylhomocysteinase family.|||Binds 1 NAD(+) per subunit.|||Endoplasmic reticulum|||Forms multimers (By similarity). Forms heteromultimers with AHCYL2 (via the C-terminal region) (PubMed:19220705). Interacts (when phosphorylated) with ITPR1 (when not phosphorylated); the interaction suppresses inositol 1,4,5-trisphosphate binding to ITPR1 (PubMed:23542070). Interacts with BCL2L10; this strengthens the interaction of AHCYL1 with ITPR1 (By similarity). Interacts with CFTR and SLC26A6; the interactions take place once AHCYL1 is released from ITPR1 and increase CFTR and SLC26A6 activities (PubMed:19033647, PubMed:21317537, PubMed:23542070). Interacts with RRM1; in a phosphorylation- and (dATP)-dependent manner. Interacts (via PEST domain when phosphorylated) with SLC4A4 isoform 1 but not isoform 2; the interaction increases SLC4A4 isoform 1 activity (PubMed:16769890, PubMed:19033647, PubMed:21317537). Interacts (when phosphorylated) with SLC9A3; the interaction is required for SLC9A3 apical location and activity (PubMed:19224921). Interacts (when phosphorylated) with FIP1L1; the interaction is direct and associates AHCYL1 with the CPSF complex and RNA Interacts with PAPOLA (By similarity). Interacts with ZCCHC4 (By similarity). Interacts with AHCY (By similarity).|||In spite of its similarity with AHCY, which catalyzes the reversible hydrolysis of S-adenosyl-L-homocysteine to adenosine and homocysteine, recombinant AHCYL1 expressed in bacteria shows no hydrolase activity, nor does it affect the enzyme activity of AHCY.|||Microsome|||Multifaceted cellular regulator which coordinates several essential cellular functions including regulation of epithelial HCO3(-) and fluid secretion, mRNA processing and DNA replication. Regulates ITPR1 sensitivity to inositol 1,4,5-trisphosphate, competing for the common binding site and acting as endogenous 'pseudoligand' whose inhibitory activity can be modulated by its phosphorylation status. Promotes the formation of contact points between the endoplasmic reticulum (ER) and mitochondria, facilitating transfer of Ca(2+) from the ER to mitochondria (By similarity). Under normal cellular conditions, functions cooperatively with BCL2L10 to limit ITPR1-mediated Ca(2+) release but, under apoptotic stress conditions, dephosphorylated which promotes dissociation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes, inhibits BCL2L10 interaction with ITPR1 and leads to increased Ca(2+) transfer to mitochondria which promotes apoptosis (By similarity). In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1 (By similarity). When extracellular stimuli induce ITPR1 phosphorylation or inositol 1,4,5-trisphosphate production, dissociates from ITPR1 to interact with CFTR and SLC26A6, mediating their synergistic activation by calcium and cAMP that stimulates the epithelial secretion of electrolytes and fluid (PubMed:12525476, PubMed:23542070). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(-) secretion (PubMed:19224921). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (PubMed:19033647, PubMed:21317537). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2. Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition. May modulate the polyadenylation state of specific mRNAs, both by controlling the subcellular location of FIP1L1 and by inhibiting PAPOLA activity, in response to a stimulus that alters its phosphorylation state. Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (By similarity). In vitro does not exhibit any S-adenosyl-L-homocysteine hydrolase activity (PubMed:12525476).|||Phosphorylated at Ser/Thr residues between Ser-68 and Thr-72 in the PEST region: required for interaction with dATP-bound RRM1 and ITPR1. Phosphorylation at Ser-68 by PRKD1 and CAMK4 is required for further phosphorylations by CSNK1A1. Phosphorylation is induced by oxidative stress. Probably phosphorylated by CAMK2A; phosphorylation at Ser-68 may be required for interaction with SLC9A3. Dephosphorylated in response to apoptotic stress conditions which causes translocation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes and promotes apoptosis.|||The PEST region is essential for the interaction with ITPR1, and, when phosphorylated, is also the RRM1-binding region. The PDZ-binding region is required for maximal interaction with ITPR1 and is also responsible for the IP3-insensitive interaction with ITPR1.|||Widely expressed (at protein level). Expressed in the lateral and luminal poles of the pancreatic duct (at protein level).|||cytosol http://togogenome.org/gene/10090:Irgq ^@ http://purl.uniprot.org/uniprot/Q8VIM9 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Fgf22 ^@ http://purl.uniprot.org/uniprot/A0A7U3JW52|||http://purl.uniprot.org/uniprot/Q9ESS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Interacts with FGFR1 and FGFR2. Interacts with FGFBP1 (By similarity).|||Plays a role in the fasting response, glucose homeostasis, lipolysis and lipogenesis. Can stimulate cell proliferation (in vitro). May be involved in hair development.|||Preferentially expressed in skin; low expression in brain. Expressed in the inner root sheath of the hair follicle.|||Secreted http://togogenome.org/gene/10090:Dnajc2 ^@ http://purl.uniprot.org/uniprot/P54103 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation.|||Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2 (By similarity). Interacts (via ZRF1-UBD region) with ID1 (PubMed:10581180, PubMed:7559602).|||Expressed in all tissues.|||Nucleus|||Phosphorylated in M (mitotic) phase.|||The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub.|||cytosol http://togogenome.org/gene/10090:Syne2 ^@ http://purl.uniprot.org/uniprot/Q6ZWQ0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nesprin family.|||C-terminal isoforms are highly expressed in the brain, hert and skeletal muscle. Isoform 1 (Nesprin-2 Giant) is most prevalent in the brain, skin, kidney and skeletal muscle.|||Cell membrane|||Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, some LINC complex constituents are tissue- or cell type-specific. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. The SUN2:SYNE2/KASH2 complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE2/KASH2 peptides bind at the interface of adjacent SUN domains. Interacts with EMD, LMNA, MKS3 and F-actin via its N-terminal domain. Interacts with DCTN1 and DYNC1I1/2; suggesting the association with the dynein-dynactin motor complex. Associates with kinesin motor complexes. Interacts with TMEM67. Interacts (via KASH domain) with TMEM258 (By similarity). Interacts with BROX; this interaction promotes SYN2 ubiquitination and facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site (By similarity).|||Mitochondrion|||Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 seem to act redundantly in cerebellum, midbrain, brain stem, and other brain regions except cerebral cortex and hippocampus. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis.|||Nucleus outer membrane|||Sarcoplasmic reticulum membrane|||The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.|||The disulfid bond with SUN2 is required for stability of the SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required for the interaction.|||cytoskeleton|||nucleoplasm http://togogenome.org/gene/10090:Bccip ^@ http://purl.uniprot.org/uniprot/Q9CWI3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BCP1 family.|||During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole (PubMed:28394342). May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ) (By similarity).|||Expressed in the testes (at protein level).|||Interacts with BRCA2, CDKN1A and MTDH/LYRIC. Interacts with DCTN1/p150-glued and ACTR1A/ARP1. Interacts with alpha-, beta- and gamma-tubulins. Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function (By similarity).|||Nucleus|||centriole|||spindle pole http://togogenome.org/gene/10090:Mark4 ^@ http://purl.uniprot.org/uniprot/Q8CIP4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-214.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cytoplasm|||Hyperphagia, hyperactivity and hypermetabolism leading to protection from diet-induced obesity, and improved glucose homeostasis due to up-regulation of AMPK kinase activity.|||Interacts with MAPT/TAU (By similarity). Interacts with gamma-tubulin (By similarity). Interacts with ODF2 (By similarity). Interacts with USP9X (By similarity). Interacts with YWHAQ (By similarity). Interacts with NLRP3; promoting NLRP3 recruitment to microtubule organizing center (MTOC) (PubMed:28656979).|||Isoform 1 and isoform 2 show similar expression patterns in the central nervous system and are present in the same subsets of neurons including pyramidal and non-pyramidal neurons in the cerebral cortex and hippocampus, cerebellar Purkinje cells, and interneurons and motor neurons in the spinal cord but not in glial cells (at protein level) (PubMed:16973293). Isoform 2 is the major isoform in brain and cerebellum (PubMed:16973293, PubMed:15009667). Also expressed in spleen, liver, small intestine, colon, kidney, tongue, testis and lung (PubMed:16973293, PubMed:15009667). Isoform 1 and isoform 2 are expressed at similar levels in heart (PubMed:16973293).|||Phosphorylated at Thr-214 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylated throughout the cell cycle.|||Serine/threonine-protein kinase (By similarity). Phosphorylates the microtubule-associated protein MAPT/TAU (By similarity). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (By similarity). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (By similarity). Required for the initiation of axoneme extension during cilium assembly (By similarity). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (By similarity). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (By similarity). Reduces neuronal cell survival (By similarity). Plays a role in energy homeostasis by regulating satiety and metabolic rate (PubMed:22992738). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (PubMed:24989893). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (By similarity). Involved in NLRP3 positioning along microtubules by mediating NLRP3 recruitment to microtubule organizing center (MTOC) upon inflammasome activation (PubMed:28656979).|||Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X (By similarity).|||centrosome|||cilium axoneme|||cilium basal body|||dendrite|||microtubule organizing center http://togogenome.org/gene/10090:Dpt ^@ http://purl.uniprot.org/uniprot/Q9QZZ6 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dermatopontin family.|||Induced by cell quiescence.|||Interacts with TGFB1, DCN and collagen.|||Mice have reduced skin elasticity, a decrease in skin-thickness, and lower collagen content in the skin.|||Seems to mediate adhesion by cell surface integrin binding. May serve as a communication link between the dermal fibroblast cell surface and its extracellular matrix environment. Enhances TGFB1 activity (By similarity). Inhibits cell proliferation. Accelerates collagen fibril formation, and stabilizes collagen fibrils against low-temperature dissociation.|||Sulfated on tyrosine residue(s).|||extracellular matrix http://togogenome.org/gene/10090:Cebpzos ^@ http://purl.uniprot.org/uniprot/Q8BTE5 ^@ Subcellular Location Annotation ^@ Mitochondrion membrane http://togogenome.org/gene/10090:Noxred1 ^@ http://purl.uniprot.org/uniprot/Q9D3S5 ^@ Function|||Similarity ^@ Belongs to the pyrroline-5-carboxylate reductase family.|||Probable oxidoreductase. http://togogenome.org/gene/10090:Rad50 ^@ http://purl.uniprot.org/uniprot/Q5SV02 ^@ Similarity ^@ Belongs to the SMC family. RAD50 subfamily. http://togogenome.org/gene/10090:Krt10 ^@ http://purl.uniprot.org/uniprot/A2A513|||http://purl.uniprot.org/uniprot/P02535 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Acts as a mediator of S.aureus adherence to desquamated nasal epithelial cells via clfB, and hence may play a role in nasal colonization.|||(Microbial infection) Binds S.pneumoniae PsrP, mediating adherence of the bacteria to lung cell lines.|||(Microbial infection) Interacts (via C-terminal tail domain) with the S.aureus clumping factor, clfB; this interaction probably mediates S.aureus attachment to the highly keratinized squamous epithelial cells from the nasal cavity.|||(Microbial infection) Interacts (via the C-terminal tail domain) with S.pneumoniae serine-rich repeat protein PsrP; this interaction probably mediates S.pneumoniae adherence to lung tissue and subsequent pathogenesis.|||Belongs to the intermediate filament family.|||Cell surface|||Cytoplasm|||Expressed in the skin at birth.|||Expressed in the suprabasal layers of the epidermis throughout the entire sole (at protein level) (PubMed:24751727, PubMed:26603179). Expressed in the infundibular regions of the ear, the interscale regions of the tail, and the interfollicular epidermis of the back (PubMed:24751727). Expressed in lung tissue from young mice (at protein level) (PubMed:19627498).|||Heterotetramer of two type I and two type II keratins. Heterodimer with KRT1 (PubMed:24940650). Two heterodimers of KRT1 and KRT10 form a heterotetramer (By similarity). The KRT10 subunit in the heterotetramer is probably disulfide-linked (By similarity). Interacts with PLEC isoform 1C, when in a heterodimer with KRT1 (PubMed:24940650).|||Mice are viable and display no differences in size and body weight (PubMed:26603179). Show acanthosis, hyperkeratosis and scaling of the stratum corneum in plantar skin (PubMed:26603179). Increase in the number of epidermal cell layers and a decrease in the abundance of cytoplasmic keratin filament bundles in suprabasal cells (PubMed:24751727). Large keratohyalin granules of various shapes are evident in the upper suprabasal cells (PubMed:24751727). KRT2 aggregates form in the cytoplasm of keratinocytes (PubMed:24751727). Show no epidermal aberrations of the footpads (PubMed:26603179). Double knockout mice of KRT10 and KRT2 are viable and display no differences in size and body weight (PubMed:26603179). Show a more severe epidermis phenotype as in single KRT10 knockout mice (PubMed:24751727, PubMed:26603179).|||Plays a role in the establishment of the epidermal barrier on plantar skin (PubMed:26603179). Involved in the maintenance of cell layer development and keratin filament bundles in suprabasal cells of the epithelium (PubMed:24751727).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||extracellular space http://togogenome.org/gene/10090:Grina ^@ http://purl.uniprot.org/uniprot/Q9ESF4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BI1 family. LFG subfamily.|||Membrane|||Potential apoptotic regulator. http://togogenome.org/gene/10090:Gkap1 ^@ http://purl.uniprot.org/uniprot/Q9JMB0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GKAP1 family.|||Down-regulated by TNF in adipocytes (at protein level).|||Golgi apparatus|||Interacts with PRKG1 (PubMed:10671526). Interacts with IRS1 (PubMed:25586176).|||Predominantly expressed in testis. Expressed in the adipose tissue (at protein level) (PubMed:25586176). In the testis it is restricted to spermatocytes and early round spermatids. Also expressed in cardiac fibroblasts.|||Regulates insulin-dependent IRS1 tyrosine phosphorylation in adipocytes by modulating the availability of IRS1 to IR tyrosine kinase. Its association with IRS1 is required for insulin-induced translocation of SLC2A4 to the cell membrane. Involved in TNF-induced impairment of insulin-dependent IRS1 tyrosine phosphorylation. http://togogenome.org/gene/10090:Ccl24 ^@ http://purl.uniprot.org/uniprot/Q3U0A4|||http://purl.uniprot.org/uniprot/Q9JKC0 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||By interleukin-4 and allergen challenge with A.fumigatus (PubMed:11067944). By interleukin-13 (IL13) (PubMed:15647285).|||Chemotactic for resting T-lymphocytes, and eosinophils (PubMed:15647285). Has lower chemotactic activity for neutrophils but none for monocytes and activated lymphocytes. Is a strong suppressor of colony formation by a multipotential hematopoietic progenitor cell line. Binds to CCR3 (By similarity).|||Highest expression in jejunum and spleen. Lower levels found in liver and lung. No expression detected in kidney, thymus, brain or testis.|||No visible phenotype in normal conditions (PubMed:15647285). Mice display a normal base-line eosinophil levels in the hematopoietic tissues and gastrointestinal tract (PubMed:15647285). However, following intratracheal IL13 administration, mice show a profound reduction in airway eosinophilia (PubMed:15647285).|||Secreted http://togogenome.org/gene/10090:Vmn1r118 ^@ http://purl.uniprot.org/uniprot/L7N273 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Jhy ^@ http://purl.uniprot.org/uniprot/E9Q793 ^@ Function|||Tissue Specificity ^@ Expressed in the brain, specifically in hypothalamus, pineal gland, and ependymal cells of the aqueduct of Sylvius, as well as in the choroid plexus of the third ventricle. Expressed in the ependymal cells lining the lateral ventricles (at protein level).|||Required for the normal development of cilia in brain ependymal cells lining the ventricular surfaces. http://togogenome.org/gene/10090:Clca1 ^@ http://purl.uniprot.org/uniprot/Q9D7Z6 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CLCR family.|||By IL3, IL4 and IL9 in the lung. Increases in the bronchiolar epithelium of asbestos-induced fibrogenesis. Decreases in cystic fibrosis knockout mice.|||Exclusively expressed in the digestive and respiratory tracts and in the uterus (at protein level). Expressed in small intestine, colon, stomach, and uterus and slightly expressed in trachea tissue. Exclusively expressed in the mucin granule membranes of gastrointestinal, respiratory, and uterine goblet cells and other mucin-producing cells. In the colon, expressed in the surface mucous cells. In the stomach highly expressed in the surface epithelium in the pylorus. Strongly expressed in the airway epithelium of lung tissues associated with airway hyperresponsiveness (AHR).|||Glycosylated.|||May be involved in mediating calcium-activated chloride conductance. May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC.|||Mice exhibit significantly increased bronchoalveolar lavage (BAL) inflammation consisted predominantly of neutrophils; have decreased goblet cell hyperplasia as well as decreased mucus production; have decreased airway hypersensitivity after cholinergic provocation with methacholine.|||The 110 kDa translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a 75 kDa N-terminal and a 35 kDa C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.|||The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.|||extracellular space http://togogenome.org/gene/10090:Ccm2l ^@ http://purl.uniprot.org/uniprot/Q8VCC6 ^@ Similarity ^@ Belongs to the CCM2 family. http://togogenome.org/gene/10090:Ppp1r42 ^@ http://purl.uniprot.org/uniprot/Q8R1Z4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with PPP1CC isoform gamma-2; the interaction is direct. Interacts with actin, dynein, KIF5B, KIFC1 and tubulin. Associates with microtubules.|||Phosphorylated; during the first round of spermatogenesis with a marginal increase at 21 days after birth.|||Regulates phosphatase activity of protein phosphatase 1 (PP1) complexes in the testis.|||Testis-specific. Expressed in spermatids (at protein level). Testis-specific.|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Ppp2r1b ^@ http://purl.uniprot.org/uniprot/Q7TNP2 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the phosphatase 2A regulatory subunit A family.|||Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with IPO9 (By similarity). Interacts with SGO1 (By similarity). Interacts with RAF1 (By similarity).|||The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. http://togogenome.org/gene/10090:Ccdc43 ^@ http://purl.uniprot.org/uniprot/Q9CR29 ^@ Similarity ^@ Belongs to the CCDC43 family. http://togogenome.org/gene/10090:Slc22a1 ^@ http://purl.uniprot.org/uniprot/O08966 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A large substrate binding region with partially overlapping binding domains for structurally different substrates is formed by several transmembrane helix domains (TMH) including TMH 2, 4, 10 and 11, and it is alternatingly exposed to the extracellular or intracellular side during substrate transport (By similarity). Amino acids in TMH 1 confer major functional differences between human and mouse orthologs (PubMed:35469921).|||Apical cell membrane|||Basal cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cellular localization of OCT1 in the intestine and the kidney remains to be finally defined. While most authors have deduced a localization at the basolateral side of enterocytes consistent with a physiological role in organic anions uptake from the blood flow and intestinal excretion (PubMed:11463829), other studies demonstrated an apical localization (PubMed:23680637), supporting a function in intestinal absorption of organic anions and drugs (PubMed:11463829, PubMed:23680637). Similarly, contradictory findings have shown a localization to the basolateral side (By similarity) or to the apical side (By similarity) of proximal tubules (By similarity). While carnitine efflux is Na(+)-independent, carnitine uptake is significantly reduced in the absence of Na(+) (PubMed:28942964). Not able to uptake and choline in the liver (PubMed:24961373). Affinity and capacity of the transporter for endogenous substrates vary among orthologs (PubMed:34040533, PubMed:35469921). For endogenous compounds such as dopamine, histamine, serotonin and thiamine, mouse ortholog display higher affinity and capacity compared with human OCT1 (PubMed:35469921). In contrast with human ortholog, not involved in metformin efflux transport (PubMed:34040533).|||Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.|||Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10216142, PubMed:12176030, PubMed:11463829, PubMed:23458604, PubMed:24961373). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (PubMed:23458604). Primarily expressed in the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds from the blood by hepatic and renal clearance (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:11463829, PubMed:24961373). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, neurotransmitters dopamine, serotonin, noradrenaline, adrenaline and histamine, and quaternary ammonium compound such as choline (PubMed:24961373, PubMed:35469921). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:23458604). Involved in the hepatic and intestinal uptake of the vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Contributes to the influx and efflux of fatty acid carriers carnitines and acylcarnitines across the basolateral membrane of hepatocytes, from the liver to the systemic circulation and inversely and may be involved in regulating the systemic availability of hepatic acylcarnitines (PubMed:28942964, PubMed:34040533). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (By similarity). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (By similarity). Also mediates the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11463829).|||Expressed in kidney (PubMed:8854860, PubMed:11463829, PubMed:16381671, PubMed:23680637, PubMed:28942964). Expressed in liver (PubMed:8854860, PubMed:11463829, PubMed:16381671, PubMed:24961373, PubMed:28942964). In liver, mainly expressed in the central vein (PubMed:24961373). Expressed in intestines (PubMed:11463829, PubMed:23680637, PubMed:28942964). Weakly expressed in adrenals and in lacting mammary glands (PubMed:8854860).|||Increased by PPARA and PPARG treatment in both liver and H35 cells.|||Involved in the uptake of clinically used drugs including diabete treatment medicine metformin, neurotoxins 1-methyl-4-phenylpyridinium (MPP(+)) and iobenguane and platinum-based drug cisplatin (PubMed:12176030, PubMed:11463829, PubMed:23458604, PubMed:24961373, PubMed:28942964). Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis (PubMed:24961373). Plays a role in the anticancer activity of cisplatin and may contribute to antitumor specificity (By similarity).|||Knockout mice appeared to be viable, healthy and fertile, and displayed no obvious phenotypic abnormalities (PubMed:11463829). Showed slightly greater body weights after 16 weeks compared to wild-type mice (PubMed:24961373). Reduced hepatic uptake and intestinal excretion of organic cations (PubMed:11463829). Showed reduced thiamine and thiamine vitamers levels in liver and intestine and higher levels of thiamine and vitamers in plasma compared to wild-type mice (PubMed:24961373). Also showed increased ratio of AMP to ATP, activation of the energy sensor AMP-activated kinase (AMPK) and increased fatty acid oxidation in the liver, which contributes to reduced hepatic triglyceride (TG) levels (PubMed:24961373). Circulating triglyceride levels were not changed (PubMed:24961373).|||Lateral cell membrane|||Phosphorylated.|||Phosphorylation of the transporter leads to changes in its substrate affinity, resulting in a regulation of the transport activity. In contrast with rat ortholog, ASP uptake is inhibited by protein kinase A (PKA) and C (PKC) activation. ASP uptake is also endogenously activated by calmodulin, the calmodulin-dependent kinase II and LCK tyrosine kinase (By similarity). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT1 (By similarity).|||Weakly expressed 2 days before birth, but gradually increased during the first 3 weeks of age, reaching a plateau around day 22 in both kidney and liver. At 45 days of age, renal and hepatic levels is 4 to 6 times higher than the level immediately after birth. http://togogenome.org/gene/10090:Ifit1 ^@ http://purl.uniprot.org/uniprot/Q64282 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IFIT family.|||By type I interferons, dsRNAs and viruses.|||Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT2 and IFIT3 (By similarity). Interacts with EIF3E (By similarity). Interacts (via TPR repeats 1-4) with RPL15 (By similarity). Interacts with STING1/MITA and disrupts its interaction with MAVS or TBK1 (By similarity). Interacts with EIF3C. Interacts (via TPR repeats 4-7) with EEF1A1.|||Cytoplasm|||ISGylated.|||Interferon-induced antiviral RNA-binding protein that specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs and inhibiting expression of viral messenger RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism).|||Phosphorylated.|||RNA recognition is mediated by a convoluted intramolecular fold of the TPR repeats (TPR eddy), which scaffolds unique additional helices that form an RNA binding cleft. http://togogenome.org/gene/10090:Fibcd1 ^@ http://purl.uniprot.org/uniprot/A2AV25 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acetyl group-binding receptor which shows a high-affinity and calcium-dependent binding to acetylated structures such as chitin, some N-acetylated carbohydrates, and amino acids, but not to their non-acetylated counterparts. Can facilitate the endocytosis of acetylated components (By similarity).|||Homotetramer; disulfide-linked.|||Membrane http://togogenome.org/gene/10090:Tmem30c ^@ http://purl.uniprot.org/uniprot/Q9D4D7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CDC50/LEM3 family.|||Membrane|||Specifically expressed in testis. http://togogenome.org/gene/10090:Usp25 ^@ http://purl.uniprot.org/uniprot/P57080 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated.|||At 13.5 dpc and 16.5 dpc, expression in the brain correlates with the proliferate ventricular zone and post-mitotic neurons of the intermediate zone, particularly in the forebrain. More marked expression at 16.5 dpc in the telencephalic septum and in the pallium. In myocytes, expressed throughout differentiation of myotubes.|||Belongs to the peptidase C19 family.|||Cytoplasm|||Deubiquitinating enzyme that hydrolyzes ubiquitin moieties conjugated to substrates and thus, functions to process newly synthesized Ubiquitin, to recycle ubiquitin molecules or to edit polyubiquitin chains and prevents proteasomal degradation of substrates. Hydrolyzes both 'Lys-48'- and 'Lys-63'-linked tetraubiquitin chains (By similarity).|||Highly expressed in testis especially in primary and secondary spematocytes and in immature spermatids. Also found in brain, skeletal muscle, liver and heart.|||Homodimer or oligomer (By similarity). Interacts with ACTA1 (via its C-terminus); the interaction occurs for all isoforms but is strongest for isoform USP25m in muscle differentiating cells. Interacts (isoform USP25m only) with MYBPC1; the interaction prevents proteasomal degradation of MYBPC1. Interacts (isoform USP25m only) with FLNC (via filament repeats 17-18, 20-21 and 24). Interacts with GAPDH. Interacts with SUMO3; the interaction sumoylates efficiently USP25. Interacts with SUMO2; the interaction sumoylates efficiently USP25. Interacts with SUMO1; the interaction only weakly sumoylates USP25. Interacts with SYK; phosphorylates USP25 and regulates USP25 intracellular levels (By similarity).|||Induced by type I interferons (IFNA and IFNB1) produced in response to lipopolysaccharide (LPS) and viral infection (HIV-1 and SeV viruses) (at protein level).|||Nucleus|||Phosphorylation in the C-terminal by SYK regulates USP25 cellular levels.|||Preferentially monoubiquitinated but can also be polyubiquitinated. Autodeubiquitinated. Ubiquitination activates the enzymatic activity either by preventing sumoylation or by allowing novel interactions (By similarity).|||Sumoylation impairs binding to and hydrolysis of ubiquitin chains. Sumoylated preferentially with SUMO2 or SUMO3. Desumoylated by SENP1. Regulated by ubiquitination on the same residue (By similarity).|||The muscle-specific isoform (USP25m) may have a role in the regulation of muscular differentiation and function. http://togogenome.org/gene/10090:Aars ^@ http://purl.uniprot.org/uniprot/Q3UD67|||http://purl.uniprot.org/uniprot/Q8BGQ7 ^@ Cofactor|||Disease Annotation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.|||Binds 1 zinc ion per subunit.|||Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala) (PubMed:16906134, PubMed:20010690, PubMed:25422440, PubMed:27622773). Also edits incorrectly charged tRNA(Ala) via its editing domain (PubMed:16906134, PubMed:20010690, PubMed:25422440, PubMed:29769718).|||Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.|||Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.|||Cytoplasm|||ISGylated.|||In sticky (sti); homozygous mice display an unkempt sticky appearance of fur and show cerebellar Purkinje cell loss and ataxia. Defects are caused by impaired ability to edit incorrectly charged tRNA(Ala), resulting in a two-fold increase in Ser-mischarged tRNA(Ala). This results in formation of ubiquitinated protein aggregates in cerebellar Purkinje cells and degeneration of these neurons.|||Monomer (By similarity). Interacts with ANKRD16; the interaction is direct (PubMed:29769718).|||Monomer. Interacts with ANKRD16; the interaction is direct.|||Was named 'sticky' because of the sticky characteristics of the fur in mice homozygous for the Glu-734 variant. http://togogenome.org/gene/10090:Pappa ^@ http://purl.uniprot.org/uniprot/Q8R4K8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M43B family.|||Binds 1 zinc ion per subunit.|||Detected in kidney, spleen, brain, ovary, breast, skin, prostate, uterus, and placenta.|||Homodimer; disulfide-linked. In pregnancy serum, predominantly found as a disulfide-linked 2:2 heterotetramer with the proform of PRG2 (By similarity).|||Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF. Isoform 2 cleaves IGFBP-4 very slowly compared to PAPP-A, but its ability to cleave IGFBP-5 is unaffected.|||Secreted http://togogenome.org/gene/10090:Or2r11 ^@ http://purl.uniprot.org/uniprot/Q8VF80 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Evx1 ^@ http://purl.uniprot.org/uniprot/P23683 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the even-skipped homeobox family.|||May play a role in the specification of neuronal cell types. May play a role in the dorsoventral specification of mesodermal cell fate.|||Nucleus|||Shows a graded distribution in the primitive streak and in cells lateral to it. It is not detected in cells along the A-P axis of the embryo anterior to the primitive streak, except at 7.5 dpc when there is transient expression in the head process. The highest levels of expression are found within the proximal (posterior) portion of the primitive streak and cells near it, with expression levels decreasing more distally (anteriorly). http://togogenome.org/gene/10090:Lrrn4 ^@ http://purl.uniprot.org/uniprot/P59383 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ May play an important role in hippocampus-dependent long-lasting memory.|||Membrane|||Mice are viable and fertile, but show impaired memory retention. Lrrn4-deficient mice are able to maintain memories for one day in hippocampus-dependent learning tasks, but are unable to retain memories for four days after learning. In contrast, in hippocampus-independent tasks Lrrn4-deficient mice normally retain memories for at least seven days. http://togogenome.org/gene/10090:Taar7d ^@ http://purl.uniprot.org/uniprot/Q5QD10 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Rtn1 ^@ http://purl.uniprot.org/uniprot/Q05CD8|||http://purl.uniprot.org/uniprot/Q4FJL2|||http://purl.uniprot.org/uniprot/Q4FZ95|||http://purl.uniprot.org/uniprot/Q7M6W1|||http://purl.uniprot.org/uniprot/Q8K0T0 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ At 12.5 dpc-14.5 dpc, strongly expressed in radial glial fibers, which are a scaffold for migrating neurons (at protein level).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.|||Interacts with NDRG1. Interacts with BACE1. Interacts with TMEM33.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Btn1a1 ^@ http://purl.uniprot.org/uniprot/Q3UM26|||http://purl.uniprot.org/uniprot/Q3UQC0|||http://purl.uniprot.org/uniprot/Q62556 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Expression increases during the last half of pregnancy and is maximal during lactation.|||May function in the secretion of milk-fat droplets. May act as a specific membrane-associated receptor for the association of cytoplasmic droplets with the apical plasma membrane (By similarity). Inhibits the proliferation of CD4 and CD8 T-cells activated by anti-CD3 antibodies, T-cell metabolism and IL2 and IFNG secretion.|||Membrane|||N-glycosylated.|||Seems to associate with xanthine dehydrogenase/oxidase.|||Strongly expressed in lactating mammary tissue (at protein level). About 100-fold lower levels in virgin mammary tissue. Also detected in spleen and thymus at 10-20 times lower levels compared to those detected in virgin mammary gland. Very low levels in several other tissues, including brain, heart, kidney, lymph node, lung and small intestine. In the thymus, detected in the stroma, in epithelial cells (at protein level). Most prominent in medullary areas of the thymus and at the corticomedullary junction (at protein level). http://togogenome.org/gene/10090:Fchsd2 ^@ http://purl.uniprot.org/uniprot/Q3USJ8 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a role in endocytosis via clathrin-coated pits. Contributes to the internalization of cell surface receptors, such as integrin ITGB1 and transferrin receptor. Promotes endocytosis of EGFR in cancer cells, and thereby contributes to the down-regulation of EGFR signaling. Recruited to clathrin-coated pits during a mid-to-late stage of assembly, where it is required for normal progress from U-shaped intermediate stage pits to terminal, omega-shaped pits. Binds to membranes enriched in phosphatidylinositol 3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate (By similarity). When bound to membranes, promotes actin polymerization via its interaction with WAS and/or WASL which leads to the activation of the Arp2/3 complex (PubMed:23437151). Does not promote actin polymerisation in the absence of membranes (By similarity).|||Cell junction|||Cell membrane|||Cytoplasm|||Detected in brain cortex at 15.5 dpc and in neonates, but levels decrease 16.5 days after birth and are very low in adult brain cortex (at protein level).|||Detected in inner ear vestibula and in stereocilia in cochlear hair cell bundles (at protein level). Ubiquitous. Detected in testis, liver, brain cortex, cerebellum, kidney, organ of Corti, utricle, spiral ganglion, tongue and eye.|||Homodimer (Probable). Interacts (via SH3 domain 2) with ITSN1 (via SH3 domain 4). Recruited to clathrin-coated pits during a mid-to-late stage of assembly via interaction with ITSN1 (By similarity). Interacts (via SH3 domain 1) with WASL (PubMed:23437151, PubMed:29887380). Interacts with WAS (PubMed:23437151). Interacts with CASK and MAGI1. CASK inhibits interaction with MAGI1 (By similarity).|||Phosphorylated. Phosphorylation on a Ser residue is important for recruitment to the cell membrane and for its role in promoting endocytosis.|||Recruited to clathrin-coated pits via SH3 domain 2.|||The F-BAR domain has an atypical, flat shape and binds preferentially to flat membranes (By similarity). Upon heterologous expression, the isolated F-BAR domain is localized at the cell membrane, and causes the formation of cellular protrusions (PubMed:23761074, PubMed:26686642).|||The two SH3 domains cooperate to maintain the protein in an autoinhibited conformation that prevents promiscuous membrane binding.|||clathrin-coated pit|||stereocilium http://togogenome.org/gene/10090:Dennd1c ^@ http://purl.uniprot.org/uniprot/Q8CFK6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Exhibits low nucleotide-independent RAB35-binding activity. Interacts with clathrin heavy chain/CLTC and with AP2A2, but not with AP2B1.|||Guanine nucleotide exchange factor (GEF) which may activate RAB8A, RAB13 and RAB35. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form.|||clathrin-coated vesicle|||cytosol http://togogenome.org/gene/10090:Gm20918 ^@ http://purl.uniprot.org/uniprot/J3QN17 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Tvp23a ^@ http://purl.uniprot.org/uniprot/Q6NVH0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TVP23 family.|||Membrane http://togogenome.org/gene/10090:Psmb5 ^@ http://purl.uniprot.org/uniprot/O55234 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1B family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity.|||Cytoplasm|||Expressed in uterus at the embryo implantation site.|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). Directly interacts with POMP (By similarity). Interacts with ABCB1 and TAP1 (By similarity).|||Up-regulated in embryonic fibroblasts and neuroblastoma cells by antioxidants through the Nrf2-ARE pathway (at protein level). Up-regulated by the antioxidant dithiolethione (D3T) in liver, small intestine and brain (at protein level). Down-regulated under lithium treatment. http://togogenome.org/gene/10090:Adamts7 ^@ http://purl.uniprot.org/uniprot/F6UD05|||http://purl.uniprot.org/uniprot/Q68SA9|||http://purl.uniprot.org/uniprot/Q6PD18 ^@ Caution|||Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Interacts with COMP.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be cleaved by a furin endopeptidase (By similarity). The precursor is sequentially processed.|||Metalloprotease that may play a role in the degradation of COMP.|||N-glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs. N- and C-glycosylations can also facilitate secretion (By similarity). O-glycosylated proteoglycan. Contains chondroitin sulfate.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme (By similarity).|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Nsg1 ^@ http://purl.uniprot.org/uniprot/Q62092 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 17.5 dpc, highly expressed in the cortical plate and in the subplate (SP).|||Belongs to the NSG family.|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Endosome membrane|||Forms a complex with GRIP1, GRIA2 and STX12 through direct interaction with GRIP1; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. Interacts with STX12 (PubMed:12070131). Interacts with APP; could regulate APP processing (PubMed:21084623). Interacts with FAM171A1 (By similarity).|||Golgi stack membrane|||Late endosome membrane|||Lysosome lumen|||Membrane|||Pituitary and less in adrenal gland and testis. Expressed in the hippocampus throughout development. At P0, highly and broadly expressed throughout the cortical plate, but is down-regulated overall at P8 and P14, but remains relatively enriched in layer V. At P0 is expressed ubiquitously in the developing cerebellum namely Purkinje neurons as well as granule neurons. However, it becomes restricted to Purkinje cells by P8. This exclusive expression in Purkinje cells is maintained throughout adulthood.|||Plays a role in the recycling mechanism in neurons of multiple receptors, including AMPAR, APP and L1CAM and acts at the level of early endosomes to promote sorting of receptors toward a recycling pathway (PubMed:15187090, PubMed:12070131, PubMed:21084623, PubMed:16037816). Regulates sorting and recycling of GRIA2 through interaction with GRIP1 and then contributes to the regulation of synaptic transmission and plasticity by affecting the recycling and targeting of AMPA receptors to the synapse (PubMed:16037816). Is required for faithful sorting of L1CAM to axons by facilitating trafficking from somatodendritic early endosome or the recycling endosome (By similarity). In an other hand, induces apoptosis via the activation of CASP3 in response to DNA damage (By similarity).|||Recycling endosome membrane|||dendrite|||multivesicular body membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Nim1k ^@ http://purl.uniprot.org/uniprot/Q8BHI9 ^@ Activity Regulation|||Similarity ^@ Activated by phosphorylation at Thr-229, probably by autophosphorylation.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Nt5c3b ^@ http://purl.uniprot.org/uniprot/Q3UFY7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pyrimidine 5'-nucleotidase family.|||Cytoplasm|||Monomer.|||Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate. The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids. Also has weak activity for CMP. UMP and purine nucleotides are poor substrates (By similarity). http://togogenome.org/gene/10090:Cacna2d2 ^@ http://purl.uniprot.org/uniprot/A0A411ACW5|||http://purl.uniprot.org/uniprot/A0A411ACX9|||http://purl.uniprot.org/uniprot/A0A411ACZ2|||http://purl.uniprot.org/uniprot/Q6PHS9 ^@ Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel subunit alpha-2/delta family.|||Binds gabapentin, an antiepileptic drug.|||Defects in Cacna2d2 are the cause of ducky phenotype (du). Du mice have spike-wave seizures characteristic of absence epilepsy and ataxia, with accompanying decreased calcium channel current in cerebellar Purkinje cells.|||Dimer formed of alpha-2-2 and delta-2 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (Probable).|||May be proteolytically processed into subunits alpha-2-2 and delta-2 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role. According to PubMed:11306709, it is processed, at least in vitro, while according to PubMed:17052222, it is only poorly processed in vivo.|||Membrane|||Mice exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities.|||N-glycosylated.|||Predominantly expressed in brain in a restricted pattern. Also expressed at lower level in kidney and testis Not expressed in lung at any moment of development. In brain, it localizes to sections of P21 brain. Expressed at high level in the cerebellum, with moderate levels in medulla, pons, and striatum. Also expressed in cortex, hippocampus, habenula and nucleus reticularis thalami (nRT). Strongly expressed in cerebellar Purkinje cells.|||The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.|||The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). http://togogenome.org/gene/10090:Gmcl1 ^@ http://purl.uniprot.org/uniprot/Q920G9 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highest levels in pachytene and diplotene stage spermatocytes and primordial germ cells of the male and the female.|||Interacts with TMPO-Beta, TSG101 and TFDP2. Interacts with EMD (By similarity).|||Nucleus matrix|||Possible function in spermatogenesis. Enhances the degradation of MDM2 and increases the amount of p53 probably by modulating the nucleocytoplasmic transport.|||Ubiquitously expressed at low levels throughout development and in adult tissues. http://togogenome.org/gene/10090:Tex55 ^@ http://purl.uniprot.org/uniprot/A6X8Z9 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Testis-specific. http://togogenome.org/gene/10090:Acyp1 ^@ http://purl.uniprot.org/uniprot/P56376|||http://purl.uniprot.org/uniprot/Q4VAF0 ^@ Similarity ^@ Belongs to the acylphosphatase family. http://togogenome.org/gene/10090:Sf3b4 ^@ http://purl.uniprot.org/uniprot/Q8QZY9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SF3B4 family.|||Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42. SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Interacts directly with SF3B2. Found in a complex with PRMT9, SF3B2 and SF3B4. The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2. Component of the minor spliceosome, which splices U12-type introns.|||Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. SF3B4 has been found in complex 'B' and 'C' as well. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.|||Nucleus http://togogenome.org/gene/10090:Jmjd1c ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ98|||http://purl.uniprot.org/uniprot/G3UZM1|||http://purl.uniprot.org/uniprot/Q69ZK6 ^@ Cofactor|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Aberrant splicing.|||Belongs to the JHDM2 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.|||Nucleus|||Probable histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May be involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes (By similarity). http://togogenome.org/gene/10090:Usp3 ^@ http://purl.uniprot.org/uniprot/E9Q8W9|||http://purl.uniprot.org/uniprot/Q3TT00|||http://purl.uniprot.org/uniprot/Q91W36 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Belongs to the peptidase C19 family. USP3 subfamily.|||Both protease activity and an intact zinc finger are required for H2A monodeubiquitination.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Hydrolase that deubiquitinates monoubiquitinated target proteins such as histone H2A and H2B. Required for proper progression through S phase and subsequent mitotic entry. May regulate the DNA damage response (DDR) checkpoint through deubiquitination of H2A at DNA damage sites. Associates with the chromatin (By similarity).|||Interacts (via UBP-type domain) with H2A; the interaction is less efficient than with monoubiquitinated H2A.|||Nucleus http://togogenome.org/gene/10090:Mtfr1 ^@ http://purl.uniprot.org/uniprot/Q3TTQ5|||http://purl.uniprot.org/uniprot/Q99MB2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MTFR1 family.|||May play a role in mitochondrial aerobic respiration. May also regulate mitochondrial organization and fission.|||Mice are viable and fertile. However, oxidative DNA damages appear in the testis, associated with a reduced expression of genes encoding enzymes with oxidoreductase activity.|||Mitochondrion|||Plays a role in mitochondrial aerobic respiration. Regulates mitochondrial organization and fission.|||Ubiquitously expressed with higher expression in testis. http://togogenome.org/gene/10090:Tpgs1 ^@ http://purl.uniprot.org/uniprot/Q99MS8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Broadly expressed at low levels. Highly expressed in brain. Present in brain neurons (at protein level).|||In testis, expression strongly increases at P22.|||Male mice are sterile due to defects in the development of the spermatid flagellum. They have reduced body fat content and fail to attack each other when caged together with other males.|||Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1 (PubMed:12972506). Interacts with PCM1, CSTPP1 and LRRC49 (By similarity).|||Subunit of the tubulin polyglutamylase complex (TPGC). The complex mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility (PubMed:12242242, PubMed:12972506, PubMed:15890843). May act in the targeting of the tubulin polyglutamylase complex. Required for the development of the spermatid flagellum.|||axon|||centrosome|||cilium axoneme|||cilium basal body|||dendrite|||flagellum axoneme|||flagellum basal body http://togogenome.org/gene/10090:Sh3d19 ^@ http://purl.uniprot.org/uniprot/Q91X43 ^@ Caution|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in hair follicles.|||Interacts with ADAM12. Isoform 2 (but not isoform 1) interacts with ADAM9, ADAM10, ADAM15 and ADAM17. Interacts with SH3GL1 SH3 domain. Interacts via SH3 3 and SH3 4 or SH3 4 and SH3 5 domains with SOS2. Probably forms a trimeric complex with SH3GL1 and SOS2 (By similarity). Interacts with SH3YL1.|||It is uncertain whether Met-1 or Met-4 is the initiator.|||May play a role in regulating A disintegrin and metalloproteases (ADAMs) in the signaling of EGFR-ligand shedding. May be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1. Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity).|||Sequence contamination. Potential vector sequence. http://togogenome.org/gene/10090:Or52n5 ^@ http://purl.uniprot.org/uniprot/Q8VGU9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H2bc7 ^@ http://purl.uniprot.org/uniprot/P10853 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Unc93b1 ^@ http://purl.uniprot.org/uniprot/E9PYK0|||http://purl.uniprot.org/uniprot/Q8VCW4 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the unc-93 family.|||Endoplasmic reticulum membrane|||Endosome|||Interacts with TLR3, TLR5, TLR7, TLR8, TLR9 and TLR13 (probably via transmembrane domain).|||Lysosome|||Membrane|||N-glycosylated.|||Plays an important role in innate and adaptive immunity by regulating nucleotide-sensing Toll-like receptor (TLR) signaling. Required for the transport of a subset of TLRs (including TLR3, TLR7 and TLR9) from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signaling cascades. May play a role in autoreactive B-cells removal.|||Upon interleukin-4 treatment in B-cells.|||phagosome http://togogenome.org/gene/10090:Sae1 ^@ http://purl.uniprot.org/uniprot/Q9R1T2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-activating E1 family.|||Broadly expressed, with highest levels in testis.|||Heterodimer of SAE1 and UBA2/SAE2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with UBE2I (By similarity).|||Nucleus|||The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2 (By similarity). http://togogenome.org/gene/10090:H2al1b ^@ http://purl.uniprot.org/uniprot/A0A087WP11 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Cntnap4 ^@ http://purl.uniprot.org/uniprot/Q99P47 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neurexin family.|||Interacts with TIAM1.|||Presynaptic cell membrane|||Presynaptic protein involved in both dopaminergic synaptic transmission and GABAergic system, thereby participating in the structural maturation of inhibitory interneuron synapses. Involved in the dopaminergic synaptic transmission by attenuating dopamine release through a presynaptic mechanism. Also participates in the GABAergic system.|||Specifically present in developing cortical interneurons: highly expressed in cortical parvalbumin (PV) cells and midbrain dopaminergic neurons and is localized presynaptically (at protein level). Also present in the substantia nigra pars compacta (SnC) and ventral tegmental area (VTA) midbrain dopaminergic projection populations.|||Synaptic defects characterized by increased dopamine but decreased GABA signaling. A reduction in the output of cortical parvalbumin (PV)-positive GABAergic basket cells is observed, together with an increase of midbrain dopaminergic release in the nucleus accumbens. Increased dopaminergic signaling induces behavior abnormalities, characterized by severe and highly penetrant over-grooming behavior, resulting in whisker, face and sometimes body hair loss but rarely lesions. The over-grooming phenotype can be pharmacologically reversed following administration of haloperidol drug. http://togogenome.org/gene/10090:Ambn ^@ http://purl.uniprot.org/uniprot/O55189|||http://purl.uniprot.org/uniprot/Q5M8P3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Ameloblast-specific.|||Belongs to the ameloblastin family.|||Involved in the mineralization and structural organization of enamel.|||extracellular matrix http://togogenome.org/gene/10090:Smo ^@ http://purl.uniprot.org/uniprot/P56726|||http://purl.uniprot.org/uniprot/Q4VBD5|||http://purl.uniprot.org/uniprot/Q8BJN8 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||During early somite stages of embryonic development, modestly up-regulated in the cells of the node (at protein level).|||G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling. Binding of sonic hedgehog (SHH) to its receptor patched prevents inhibition of smoothened (SMO) by patched (By similarity). When active, SMO binds to and sequesters protein kinase A catalytic subunit PRKACA at the cell membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors which releases the GLI proteins from PRKACA-mediated inhibition and allows for transcriptional activation of hedgehog pathway target genes (PubMed:33886552). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (PubMed:25644602).|||Homodimer (By similarity). Interacts (via C-terminus) with protein kinase A catalytic subunit PRKACA; interacts with free PRKACA subunits and the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors (PubMed:33886552). Interacts with ARRB2 (PubMed:15618519). Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO (PubMed:22072986). Interacts with KIF7, DLG5 and SDCBP (PubMed:25644602). Interacts with GAS8/DRC4 (PubMed:21659505).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Phosphorylation by GRK kinases is required for interaction with protein kinase A catalytic subunit PRKACA.|||The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24171105, PubMed:19464178). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (PubMed:31263273). The activating sterol is likely to be cholesterol (PubMed:31263273, PubMed:35658032). The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH (PubMed:35658032).|||cilium http://togogenome.org/gene/10090:Akap10 ^@ http://purl.uniprot.org/uniprot/O88845 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase.|||Highly expressed in testis, kidney and lung, followed by brain, skeletal muscle, liver, spleen and heart. Also expressed in brown adipose tissue and pancreas.|||Membrane|||Mitochondrion|||RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer. http://togogenome.org/gene/10090:Bhlhe40 ^@ http://purl.uniprot.org/uniprot/O35185 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expressed from 9.5 dpc to 17.5 dpc in the ventricular layer of the brain and spinal cord, but also in the retinal pigment epithelium, developing eyelids, nasal epithelium, serous gland, vibrissae, epithelium of the mouth cavity and the tooth buds. Highly expressed in the heart, thymus and adrenal glands followed by lung, liver parenchyma, kidney tubules, epithelium of the esophagus and stomach. From 15.5 dpc to 17.5 dpc it is expressed in urinary bladder and urethra. From 17.5 dpc, it is expressed in developing muscle.|||Homodimer. Heterodimer with BHLHE41/DEC2. Interacts with ubiquitin-conjugating enzyme UBE2I/UBC9. Interacts with HDAC1, SUMO1, RXRA and BMAL1 (By similarity). Interacts with TCF3/E47.|||Nucleus|||Stimulated by retinoic acid (RA). Expressed in a circadian manner in the liver with a peak at ZT10.|||Sumoylation inhibits its ubiquitination and promotes its negative regulation of the CLOCK-BMAL1 heterodimer transcriptional activator activity.|||Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:18411297). Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop) (PubMed:14672706). Both these loops are interlocked as it represses the expression of PER1/2 and in turn is repressed by PER1/2 and CRY1/2 (By similarity). Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1|BMAL2 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes (By similarity). Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2 (PubMed:14672706). Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA and NR1H3/LXRA transactivation activity (PubMed:19786558). May function as a transcriptional factor for neuronal differentiation (PubMed:9284045). Represses the transcription of NR0B2 and attentuates the transactivation of NR0B2 by the CLOCK-BMAL1 complex (By similarity). Drives the circadian rhythm of blood pressure through transcriptional repression of ATP1B1 in the cardiovascular system (PubMed:30012868).|||Ubiquitinated; which may lead to proteasomal degradation. http://togogenome.org/gene/10090:Rasl12 ^@ http://purl.uniprot.org/uniprot/Q08AT1 ^@ Similarity ^@ Belongs to the small GTPase superfamily. Ras family. http://togogenome.org/gene/10090:Rhpn1 ^@ http://purl.uniprot.org/uniprot/E9Q7Q7|||http://purl.uniprot.org/uniprot/Q61085 ^@ Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RHPN family.|||Binds specifically to GTP-Rho. Interacts with ROPN1.|||Has no enzymatic activity. May serve as a target for Rho, and interact with some cytoskeletal component upon Rho binding or relay a Rho signal to other molecules.|||Highly expressed in testis.|||The PDZ domain mediates interaction with ROPN1. http://togogenome.org/gene/10090:H2-Q4 ^@ http://purl.uniprot.org/uniprot/Q0WXH7|||http://purl.uniprot.org/uniprot/Q8HWB2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Slc6a12 ^@ http://purl.uniprot.org/uniprot/G5E8Z4|||http://purl.uniprot.org/uniprot/Q8VCS9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A12 subfamily.|||Cell membrane|||Interacts with LIN7C.|||Lateral cell membrane|||Membrane http://togogenome.org/gene/10090:Phox2b ^@ http://purl.uniprot.org/uniprot/O35690 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the paired homeobox family.|||Interacts with TRIM11.|||Nucleus http://togogenome.org/gene/10090:Vmn1r228 ^@ http://purl.uniprot.org/uniprot/Q8R2A7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pon2 ^@ http://purl.uniprot.org/uniprot/Q62086 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the paraoxonase family.|||Binds 2 calcium ions per subunit.|||Capable of hydrolyzing lactones and a number of aromatic carboxylic acid esters.|||Glycosylated.|||Homotrimer.|||Membrane|||The signal sequence is not cleaved. http://togogenome.org/gene/10090:Vash2 ^@ http://purl.uniprot.org/uniprot/Q8C5G2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transglutaminase-like superfamily. Vasohibin family.|||Cytoplasm|||Interacts with SVBP; interaction enhances VASH2 tyrosine carboxypeptidase activity.|||Preferentially expressed in bone marrow-derived mononuclear cells at the sprouting front.|||Secreted|||Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146868). Acts as an activator of angiogenesis: expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis (PubMed:19204325). Plays a role in axon formation (PubMed:31235911).|||cytoskeleton http://togogenome.org/gene/10090:Miox ^@ http://purl.uniprot.org/uniprot/Q9QXN5 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the myo-inositol oxygenase family.|||Binds 2 iron ions per subunit.|||Cytoplasm|||Kidney specific. Renal proximal tubules. http://togogenome.org/gene/10090:Thbd ^@ http://purl.uniprot.org/uniprot/P15306|||http://purl.uniprot.org/uniprot/Q543W3 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endothelial cells are unique in synthesizing thrombomodulin.|||Interacts with ITGAL, ITGAM and ITGB2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated. http://togogenome.org/gene/10090:Tbc1d10b ^@ http://purl.uniprot.org/uniprot/Q8BHL3 ^@ Function|||Subcellular Location Annotation ^@ Acts as GTPase-activating protein for RAB3A, RAB22A, RAB27A and RAB35. Does not act on RAB2A and RAB6A (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Wars1 ^@ http://purl.uniprot.org/uniprot/P32921|||http://purl.uniprot.org/uniprot/Q3U6U7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Cytoplasm|||Homodimer (By similarity). Interacts with oxidized form of GAPDH (By similarity).|||Isoform 2 is widely expressed, isoform 1 is found only in embryonic stem cells.|||Proteolytic cleavage generates 2 forms; T1-TrpRS and T2-TrpRS.|||T1-TrpRS has aminoacylation activity while T2-TrpRS lacks it. T1-TrpRS and T2-TrpRS possess angiostatic activity. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression (By similarity). http://togogenome.org/gene/10090:Myt1 ^@ http://purl.uniprot.org/uniprot/B0R0C1|||http://purl.uniprot.org/uniprot/Q8CFC2 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MYT1 family.|||Binds to the promoter region of genes encoding proteolipid proteins of the central nervous system. May play a role in the development of neurons and oligodendroglia in the CNS. May regulate a critical transition point in oligodendrocyte lineage development by modulating oligodendrocyte progenitor proliferation relative to terminal differentiation and up-regulation of myelin gene transcription (By similarity).|||Contains 7 zinc fingers of the C2HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence.|||Interacts with STEAP3.|||Isoform 1 is detected in the earliest born neurons. At 9.5 dpc it is detected in the ventrolateral part of the spinal cord, which later become motor neurons and is also detected in the dispersed cells of the alar plate interneurons. During spinal cord development, the expression is highest in the latest born neurons (the subventricular zone). Detected in the early differentiated neurons within the neuroepithelium and the neural crest cells at 9.5 dpc. At 12.5 dpc, detected in the differentiated neurons within the forebrain, midbrain, and hindbrain. In these neurons, the expression level is highest in the latest born neurons and is also detected in the differentiated neurons of the sensory organs and the peripheral ganglia.|||Isoform 1 is more predominant than isoform 2 at all stages of development and adulthood. Expressed in differentiated neurons especially at higher levels in newly generated ones.|||Nucleus http://togogenome.org/gene/10090:Agps ^@ http://purl.uniprot.org/uniprot/A2AL50|||http://purl.uniprot.org/uniprot/Q8C0I1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAD-binding oxidoreductase/transferase type 4 family.|||Catalyzes the exchange of an acyl for a long-chain alkyl group and the formation of the ether bond in the biosynthesis of ether phospholipids.|||Catalyzes the exchange of the acyl chain in acyl-dihydroxyacetonephosphate (acyl-DHAP) for a long chain fatty alcohol, yielding the first ether linked intermediate, i.e. alkyl-dihydroxyacetonephosphate (alkyl-DHAP), in the pathway of ether lipid biosynthesis.|||Homodimer.|||Peroxisome|||Peroxisome membrane http://togogenome.org/gene/10090:Mocs1 ^@ http://purl.uniprot.org/uniprot/Q5RKZ7 ^@ Caution|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Binds 2 [4Fe-4S] clusters. Binds 1 [4Fe-4S] cluster coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine and 1 [4Fe-4S] cluster coordinated with 3 cysteines and the GTP-derived substrate.|||Death between days 1 and 11 after birth, due to a progressive neurological disorder caused by massive cell death. Death is caused by the absence of molybdenum cofactor, resulting in elevated sulfite and diminished sulfate levels throughout the organism. Mice do not possess any sulfite oxidase or xanthine dehydrogenase activity. No organ abnormalities are observed and the synaptic localization of inhibitory receptors appears normal. Long-term rescue results have been obtained in mice lacking Mocs1 thanks to an adeno-associated virus-mediated gene transfer.|||In the C-terminal section; belongs to the MoaC family.|||In the N-terminal section; belongs to the radical SAM superfamily. MoaA family.|||Isoform Mocs1a and isoform Mocs1b probably form a complex that catalyzes the conversion of 5'-GTP to cyclic pyranopterin monophosphate (cPMP). Mocs1a catalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate and Mocs1b catalyzes the subsequent conversion of (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate to cPMP.|||Isoform Mocs1a and isoform Mocs1b probably form a heterooligomer.|||The C-terminus of Mocs1a was previously believed to be thiocarboxylated, but it is now known not to be the case. http://togogenome.org/gene/10090:Ppp1r13b ^@ http://purl.uniprot.org/uniprot/Q62415 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ASPP family.|||Cytoplasm|||In contrast to its official gene name, it is not a regulatory subunit of protein phosphatase 1. This name was given due to its similarity with a protein that binds to protein phosphatase 1.|||Interacts with P53/TP53; the interaction promotes pro-apoptotic activity.|||Nucleus|||Regulator that plays a central role in regulation of apoptosis via its interaction with p53/TP53 (By similarity). Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo (By similarity).|||The ankyrin repeats and the SH3 domain are required for a specific interactions with TP53. http://togogenome.org/gene/10090:Rrp7a ^@ http://purl.uniprot.org/uniprot/Q9D1C9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRP7 family.|||Nucleolar protein that is involved in ribosomal RNA (rRNA) processing. Also plays a role in primary cilia resorption, and cell cycle progression in neurogenesis and neocortex development. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with NOL6; required for NOL6 localization to nucleolus.|||centrosome|||cilium|||nucleolus http://togogenome.org/gene/10090:Or8b40 ^@ http://purl.uniprot.org/uniprot/Q9EQA4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mthfd1l ^@ http://purl.uniprot.org/uniprot/Q3V3R1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Homodimer.|||In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.|||In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.|||May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2.|||Mitochondrion|||This monofunctional enzyme consists of two major domains: an N-terminal inactive methylene-THF dehydrogenase and cyclohydrolase domain and an active larger formyl-THF synthetase C-terminal domain. http://togogenome.org/gene/10090:Ppm1b ^@ http://purl.uniprot.org/uniprot/P36993|||http://purl.uniprot.org/uniprot/Q546R1|||http://purl.uniprot.org/uniprot/Q99NF7 ^@ Cofactor|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Enzyme with a broad specificity. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser-172'. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.|||Isgylation negatively regulates its activity.|||Isoform 1: Expressed ubiquitously. Isoform 2: Expressed exclusively in testis and intestine. Isoform 3: Expressed exclusively in brain and intestine. Isoform 4: Expressed exclusively in testis and intestine.|||Membrane|||Monomer. Interacts with PAK6 (By similarity). Interacts with the phosphorylated form of IKBKB/IKKB (By similarity).|||N-myristoylation is essential for the recognition of its substrates for dephosphorylation.|||Probable cloning artifact.|||cytosol http://togogenome.org/gene/10090:Fthl17e ^@ http://purl.uniprot.org/uniprot/Q3SXD1|||http://purl.uniprot.org/uniprot/Q99MX2 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the ferritin family.|||Expressed in the testes and spermatogonia.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Cwc15 ^@ http://purl.uniprot.org/uniprot/Q9JHS9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC15 family.|||Identified in the spliceosome C complex. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly with CTNNBL1 in the complex. Component of the minor spliceosome, which splices U12-type introns (By similarity).|||Involved in pre-mRNA splicing as component of the spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus http://togogenome.org/gene/10090:Acad10 ^@ http://purl.uniprot.org/uniprot/Q8K370 ^@ Function|||Similarity ^@ Acyl-CoA dehydrogenase only active with R- and S-2-methyl-C15-CoA.|||Belongs to the acyl-CoA dehydrogenase family. http://togogenome.org/gene/10090:Apol8 ^@ http://purl.uniprot.org/uniprot/A2VDH7 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Fcsk ^@ http://purl.uniprot.org/uniprot/Q7TMC8 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the GHMP kinase family.|||Has strong fucokinase activity.|||Has very weak fucokinase activity.|||Isoform 1: Expressed strongly in brain, ovary and testis, moderately in kidney and liver, and weakly in lung, spleen and heart. Isoform 2: Expressed very strongly in brain, strongly in ovary, testis and kidney, moderately in lung and liver, and weakly in heart and spleen.|||Takes part in the salvage pathway for reutilization of fucose from the degradation of oligosaccharides. http://togogenome.org/gene/10090:Ankrd45 ^@ http://purl.uniprot.org/uniprot/Q810N6 ^@ Function|||Subcellular Location Annotation ^@ Cleavage furrow|||Cytoplasm|||May play a role during cell division.|||Midbody ring http://togogenome.org/gene/10090:Scarb1 ^@ http://purl.uniprot.org/uniprot/Q61009 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD36 family.|||Both isoform 1 and isoform 2 are up-regulated in response to adrenocorticotropic hormone (ACTH).|||Cell membrane|||Expressed primarily in liver, ovary and adrenal gland, and, at lower levels in other non-placental steroidogenic tissues, including adipose tissue, mammary gland and testis (at protein level) (PubMed:8560269, PubMed:9254074, PubMed:9614139). Isoform 2 is expressed at lower levels than isoform 1 in liver, testis and adrenal gland (PubMed:9614139). At the mRNA, but not at the protein level, isoform 2 is the predominant isoform in testis (80%) (PubMed:9254074).|||N-glycosylated.|||Receptor for different ligands such as phospholipids, cholesterol ester, lipoproteins, phosphatidylserine and apoptotic cells (By similarity). Both isoform 1 and isoform 2 act as receptors for HDL, mediating selective uptake of cholesteryl ether and HDL-dependent cholesterol efflux (PubMed:9254074, PubMed:9614139). Also facilitates the flux of free and esterified cholesterol between the cell surface and apoB-containing lipoproteins and modified lipoproteins, although less efficiently than HDL. May be involved in the phagocytosis of apoptotic cells, via its phosphatidylserine binding activity (By similarity).|||The C-terminal region binds to PDZK1.|||The six cysteines of the extracellular domain are all involved in intramolecular disulfide bonds.|||caveola http://togogenome.org/gene/10090:Srp72 ^@ http://purl.uniprot.org/uniprot/F8VQC1|||http://purl.uniprot.org/uniprot/Q9CS54 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SRP72 family.|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).|||Cytoplasm http://togogenome.org/gene/10090:Aadacl2fm3 ^@ http://purl.uniprot.org/uniprot/J3QPI0 ^@ Similarity ^@ Belongs to the 'GDXG' lipolytic enzyme family. http://togogenome.org/gene/10090:Usp42 ^@ http://purl.uniprot.org/uniprot/B2RQC2 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Deubiquitinating enzyme which may play an important role during spermatogenesis.|||Expressed in the midbrain, forebrain, optic vesicles and eyes of embryos at 10.5 dpc and a more pronounced expression is seen at 12.5 dpc.|||Highest expression seen in the testis. Also expressed in brain, lung and thymus. The expression level gradually increases from 2 weeks after birth and then decreases from the pachytene spermatocyte (PS) stage during spermatogenesis. http://togogenome.org/gene/10090:Ndst2 ^@ http://purl.uniprot.org/uniprot/P52850 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. NDST subfamily.|||Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).|||Golgi apparatus membrane|||Mice are viable and fertile but have fewer connective-tissue-type mast cells; mast cells that remain having an altered morphology and severely reduced amounts of stored histamine and mast cell proteases.|||Monomer.|||The presence of 4 different heparan sulfate N-deacetylase/N-sulfotransferase enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/sulfation reactions, whereas other later on fill in or extend already modified heparan sulfate sequences.|||Widely expressed in adult and throughout development. http://togogenome.org/gene/10090:Syt9 ^@ http://purl.uniprot.org/uniprot/Q9R0N9 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.|||Homodimer; disulfide-linked via the cysteine motif (PubMed:10531343). Can also form heterodimers with SYT3, SYT6, SYT7 and SYT10 (PubMed:10531343, PubMed:10531344, PubMed:10871604). Interacts with DNAJC5 and SNAP25, but not with HSC70 (PubMed:20847230). The interaction with DNAJC5 is stimulated tenfold in presence of calcium while the interaction with SNAP25 is inhibited (PubMed:20847230).|||May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis.|||The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Synb ^@ http://purl.uniprot.org/uniprot/Q8BI41 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gamma type-C retroviral envelope protein family.|||Cell membrane|||Expressed in the placental labyrinth from stage 8.5 dpc onwards.|||Highly expressed in placenta where it localizes to syncytiotrophoblasts of the labyrinthine zona (PubMed:15644441). Specifically localizes to syncytiotrophoblast layer II (SynT-II) (PubMed:18448564). Also detected at very low levels in ovary (PubMed:15644441).|||In males, up-regulated in regenerating muscle tissue after injury.|||Synthesized as an inactive precursor that is heavily N-glycosylated and processed likely by furin in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R.|||The CXXC motif is highly conserved across a broad range of retroviral envelope proteins. It is thought to participate in the formation of a labile disulfide bond possibly with the CX6CC motif present in the transmembrane protein. Isomerization of the intersubunit disulfide bond to an SU intrachain disulfide bond is thought to occur upon receptor recognition in order to allow membrane fusion.|||The mature protein consists of a trimer of SU-TM heterodimers (Probable). The SU-TM heterodimers are attached by a labile interchain disulfide bond (By similarity).|||The mouse genome contains a high percentage of proviral-like elements, also called endogenous retroviruses (ERVs) that are the genomic traces of ancient infections of the germline by exogenous retroviruses. Although most of these elements are defective, some have conserved a functional envelope (env) gene, most probably diverted by the host for its benefit.|||This endogenous retroviral envelope protein has retained its original fusogenic properties (PubMed:15644441, PubMed:18077339, PubMed:22032925, PubMed:27589388). Together with Syna, participates in trophoblast fusion and the formation of a syncytium during placenta morphogenesis (PubMed:22032925). Synb is specifically involved in formation of syncytiotrophoblast layer II (SynT-II) (PubMed:22032925). Promotes myoblast fusion, and may play a role in regeneration of damaged muscle tissue in males (PubMed:27589388). May have immunosuppressive activity (PubMed:18077339).|||Viable, although growth is retarded and neonate numbers are reduced (PubMed:22032925). In the placental labyrinth, formation of syncytiotrophoblast layer II (SynT-II) is abnormal with reduced cell fusion and progressive expansion of maternal blood lacunae(PubMed:22032925). Unfused SynT-II cells form dense plaque-like structures between adjacent cells, which resemble cell junctions and are associated with high expression levels of GJB6/connexin-30 (PubMed:22032925). Formation of syncytiotrophoblast layer I (SynT-I) is grossly normal (PubMed:22032925). Adult male mice have a 15% reduction in muscle mass compared to wild type, probably due to defects in myoblast fusion (PubMed:27589388). Double knockouts of Syna and Synb are embryonic lethal at stage 9.5 dpc to 10.5 dpc, indicating a more severe phenotype than the Syna single knockout (PubMed:22032925). http://togogenome.org/gene/10090:Maf ^@ http://purl.uniprot.org/uniprot/P54843 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator or repressor. When overexpressed, represses anti-oxidant response element (ARE)-mediated transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Binds to the ARE sites of detoxifying enzyme gene promoters (By similarity). Involved in embryonic lens fiber cell development. Recruits the transcriptional coactivators CREBBP and/or EP300 to crystallin promoters leading to up-regulation of crystallin gene during lens fiber cell differentiation. Activates the expression of IL4 in T helper 2 (Th2) cells. Increases T-cell susceptibility to apoptosis by interacting with MYB and decreasing BCL2 expression. Together with PAX6, transactivates strongly the glucagon gene promoter through the G1 element. Activates transcription of the CD13 proximal promoter in endothelial cells. Represses transcription of the CD13 promoter in early stages of myelopoiesis by affecting the ETS1 and MYB cooperative interaction. Involved in the initial chondrocyte terminal differentiation and the disappearance of hypertrophic chondrocytes during endochondral bone development. Binds to the sequence 5'-[GT]G[GC]N[GT]NCTCAGNN-3' in the L7 promoter. Binds to the T-MARE (Maf response element) sites of lens-specific alpha- and beta-crystallin gene promoters. Binds element G1 on the glucagon promoter. Binds an AT-rich region adjacent to the TGC motif (atypical Maf response element) in the CD13 proximal promoter in endothelial cells. It may interact with additional basic-zipper proteins that determine a subtype of Maf-responsive element binding.|||Belongs to the bZIP family. Maf subfamily.|||Expressed in the floor of the diencephalon at 10 dpc (at protein level). Expressed in the midline of the forebrain and in the eye region at 9 dpc. Expressed in the head ectoderm destined to become the lens vesicle at 9 and 10 dpc. Expressed in the lens placode at 10.5 dpc. Expressed in the lens vesicle in both epithelial and fiber cells at 11 dpc. Expressed in secondary fiber cells at the equatorial region that divides the lens into anterior and posterior hemispheres between 11 and 14 dpc. Expressed in the neural tube and in primary fiber cells of the lens at 11.5 dpc. Expressed in proximal tubules of the cortex in the kidney at 16 and 17 dpc. Expressed in hypertrophic chondrocytes at 14.5 to 18.5 dpc. Expressed in the pancreas at 12.5 dpc until the adult stage.|||Expressed in tubules of the renal cortex and hepatocytes. Expressed in the lens (at protein level). Expressed in pancreatic islets and endothelial cells.|||Homodimer or heterodimer with other bHLH-Zip transcription factors. Binds DNA as a homodimer or as a heterodimer. Heterotetramer of two MAF and two USF2. Interacts with PAX6; the interaction is direct. Interacts with MYB; interaction takes place weakly in normal T-cells and increases in T-cells following stimulation through the TCR engagement. Interacts with MYB; the ternary complex formed with MYB and the CD13 promoter is regulated in response to differentiating signals. Interacts with USF2; the interaction inhibits its DNA-binding activity on the L7 promoter. Interacts with CREBBP, EP300 and ETS1 (By similarity).|||Knockout mice lacking this gene exhibit small eyes or microphthalmia with an absence of normal lens structures, an abnormal chondrocyte development, with terminal differentiation of hypertrophic chondrocytes initially delayed, followed by a subsequent expansion of the hypertrophic chondrocyte domain in the growth plates of embryonic and postnatal long bones. They also show a lack of IL4 production.|||Nucleus|||Phosphorylated by GSK3 and MAPK13 on serine and threonine residues (By similarity). The phosphorylation status can serve to either stimulate or inhibit transcription.|||Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by glucocorticoids (By similarity). http://togogenome.org/gene/10090:Asb18 ^@ http://purl.uniprot.org/uniprot/Q8VHA6 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Mmd ^@ http://purl.uniprot.org/uniprot/Q9CQY7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ADIPOR family.|||Involved in the dynamics of lysosomal membranes associated with microglial activation following brain lesion.|||Late endosome membrane|||Lysosome membrane http://togogenome.org/gene/10090:Cdhr2 ^@ http://purl.uniprot.org/uniprot/E9Q7P9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Cell junction|||Intermicrovillar adhesion molecule that forms, via its extracellular domain, calcium-dependent heterophilic complexes with CDHR5 on adjacent microvilli. Thereby, controls the packing of microvilli at the apical membrane of epithelial cells. Through its cytoplasmic domain, interacts with microvillus cytoplasmic proteins to form the intermicrovillar adhesion complex/IMAC. This complex plays a central role in microvilli and epithelial brush border differentiation. May also play a role in cell-cell adhesion and contact inhibition in epithelial cells.|||Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5. Interacts with MAST2 (By similarity). Interacts (via cytoplasmic domain) with USH1C and MYO7B; required for proper localization of CDHR2 to microvilli tips and its function in brush border differentiation (Probable).|||The cadherin 1 domain is required for binding to CDHR5.|||microvillus membrane http://togogenome.org/gene/10090:Ulk3 ^@ http://purl.uniprot.org/uniprot/Q3U3Q1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Autophosphorylation is blocked by interaction with SUFU (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.|||Cytoplasm|||Interacts (via protein kinase domain) with SUFU.|||Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy (By similarity). http://togogenome.org/gene/10090:Ift25 ^@ http://purl.uniprot.org/uniprot/Q9D6H2 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT25 family.|||Component of the IFT complex B required for sonic hedgehog/SHH signaling. May mediate transport of SHH components: required for the export of SMO and PTCH1 receptors out of the cilium and the accumulation of GLI2 at the ciliary tip in response to activation of the SHH pathway, suggesting it is involved in the dynamic transport of SHH signaling molecules within the cilium. Not required for ciliary assembly (PubMed:22595669). Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation (PubMed:28430876). Plays a role in the early development of the kidney (PubMed:29626631). May be involved in the regulation of ureteric bud initiation (PubMed:29626631).|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:19253336). Interacts with IFT27 (PubMed:28430876). Interacts with IFT88 (PubMed:19253336).|||Expressed predominantly in the testis (at protein level).|||Null mutants retain the ability to ciliate and survive through gestation. They die shortly after birth due to different phenotypes reminiscent of Shh signaling defects: polydactyly, cleft palate, lung isomerisms, and structural heart defects (PubMed:22595669). Conditional knockout in male germ cells results in infertility, abnormal sperm morphology, significantly reduced sperm count and sperm mobility and disruption of sperm lipid rafts (PubMed:28964737, PubMed:28430876). Mutant mice with germline deletion of IFT25 die shortly after birth with structural defects in most organs including the kidneys, where duplicated collecting duct system and/or duplex kidney is often observed (PubMed:29626631).|||Was initially classified as a member of the small heat shock family protein. However, it was later shown that it is not the case (PubMed:22595669).|||cilium http://togogenome.org/gene/10090:Cpne2 ^@ http://purl.uniprot.org/uniprot/P59108 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the copine family.|||Binds 3 Ca(2+) ions per C2 domain.|||Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Exhibits calcium-dependent cell membrane binding properties (PubMed:21087455, PubMed:26175110).|||Cell membrane|||Cytoplasm|||Nucleus|||The C2 domain 2, but not the C2 domain 1, is necessary for calcium-mediated membrane association (PubMed:21087455, PubMed:26175110). The linker region is necessary for calcium-dependent cell membrane association (PubMed:21087455). http://togogenome.org/gene/10090:Tekt3 ^@ http://purl.uniprot.org/uniprot/Q5SXS5|||http://purl.uniprot.org/uniprot/Q6X6Z7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tektin family.|||Expressed preferentially in testis. Expressed predominantly in late pachytene spermatocytes and early round spermatids (PubMed:14735490). Expressed in spermatozoa (PubMed:36708031).|||Interacts with TEKT1, TEKT2, TEKT4 and TEKT5.|||May be proteolytically processed during the epididymal transit of spermatozoa.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules (By similarity). Required for normal sperm mobility (PubMed:18951373).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules. Required for normal sperm mobility.|||N- and O-glycosylated.|||Sperm with reduced motility (47%) and forward progression and increased flagellar structural bending defects. However, normal fertility is maintained.|||acrosome outer membrane|||cilium axoneme|||flagellum http://togogenome.org/gene/10090:Kat2b ^@ http://purl.uniprot.org/uniprot/B2RR30|||http://purl.uniprot.org/uniprot/Q9JHD1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family. GCN5 subfamily.|||Expression is low during embryogenesis and becomes up-regulated in some adult tissues including heart and skeletal muscle.|||Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY, MAPRE1/EB1, PLK4, RRP9/U3-55K and TBX5. Acts as a circadian transcriptional coactivator which enhances the activity of the circadian transcriptional activators: NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers. Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5. Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4. Acetylates RRP9/U3-55K, a core subunit of the U3 snoRNP complex, impairing pre-rRNA processing. Acetylates MAPRE1/EB1, promoting dynamic kinetochore-microtubule interactions in early mitosis. Also acetylates spermidine.|||Interacts with BCAS3. Interacts with SIRT1. Interacts with EP300, CREBBP and DDX17. Component of a large chromatin remodeling complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and KIF11/TRIP5. Interacts with KLF1; the interaction does not acetylate KLF1 and there is no enhancement of its transactivational activity. Interacts with NFE4. Interacts with MECOM. Interacts with NR2C2 (hypophosphorylated and unsumoylated form); the interaction promotes the transactivation activity of NR2C2. Interacts with NFE4. Interacts with MECOM. Interacts with E2F1; the interaction acetylates E2F1 augmenting its DNA-binding and transcriptional activity. Interacts with NPAS2, BMAL1 and CLOCK (By similarity). Interacts (unsumoylated form) with NR2C1; the interaction promotes transactivation activity. Interacts with CEBPB (By similarity). Interacts with NR4A3 (PubMed:12709428). Interacts with TBX5 (By similarity). Interacts with PLK4 (By similarity). Interacts with RB1; this interaction leads to RB1 acetylation (PubMed:20940255).|||No visible phenotype (PubMed:11017084).|||Nucleus|||centrosome http://togogenome.org/gene/10090:Tonsl ^@ http://purl.uniprot.org/uniprot/G3UW83|||http://purl.uniprot.org/uniprot/Q6NZL6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tonsoku family.|||Chromosome|||Component of the MMS22L-TONSL complex, a complex at least composed of MMS22L and TONSL/NFKBIL2 (By similarity). Interacts with the MCM complex, the FACT complex and the RPA complex (By similarity). Interacts with MCM5; the interaction is direct (By similarity). Binds histones, with a strong preference for histone H3.1 (histones H3.1 and H3-4/H3.1t) (PubMed:35298257). Interacts (via ANK repeats) with histone H4; specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) (By similarity). May interact with DNAJC9; the interaction seems to be histone-dependent (By similarity).|||Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, TONSL acts as histone reader, which recognizes and binds newly synthesized histones following their replacement by histone chaperones. Specifically binds histone H4 lacking methylation at 'Lys-20' (H4K20me0) and histone H3.1.|||Cytoplasm|||Nucleus|||The ANK repeats mediate the interaction with the MCM complex and histones, while the LRR repeats mediate the interaction with MMS22L. http://togogenome.org/gene/10090:Mrap2 ^@ http://purl.uniprot.org/uniprot/D3Z1Q2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MRAP family.|||Cell membrane|||Endoplasmic reticulum membrane|||Homodimer and heterodimer. Forms antiparallel homodimers and heterodimers with MRAP. Interacts with MC1R, MC2R, MC3R and MC5R (By similarity). Interacts with MC4R.|||Modulator of melanocortin receptor 4 (MC4R), a receptor involved in energy homeostasis. Plays a central role in the control of energy homeostasis and body weight regulation by increasing ligand-sensitivity of MC4R and MC4R-mediated generation of cAMP. May also act as a negative regulator of MC2R: competes with MRAP for binding to MC2R and impairs the binding of corticotropin (ACTH) to MC2R. May also regulate activity of other melanocortin receptors (MC1R, MC3R and MC5R); however, additional evidence is required in vivo.|||Obesity. Mice are normal at birth, with normal weight gain and post-weaning food intake during early life, although young males trend toward greater weight and food intake with advancing age. Mice of both genders gradually become extremely obese on a diet of regular chow ad libitum.|||Predominantly expressed in the brain, mainly in the pons and cerebellum but also in regions involved in energy homeostasis, such as the hypothalamus and brainstem. http://togogenome.org/gene/10090:Map2k5 ^@ http://purl.uniprot.org/uniprot/Q9WVS7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases.|||Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A.|||Cytoplasm|||Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI. http://togogenome.org/gene/10090:Mrgpra1 ^@ http://purl.uniprot.org/uniprot/G3UW97|||http://purl.uniprot.org/uniprot/Q91WW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed in a subset of sensory neurons that includes nociceptors. Expressed in the subclass of non-peptidergic sensory neurons that are IB4(+) and VR1(-).|||Membrane|||Orphan receptor activated by a subset of RFamide-family neuropeptides such as FLRF-amide and FMRF-amide. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. May regulate the function of nociceptive neurons by modulation of pain perception. http://togogenome.org/gene/10090:Vmn1r123 ^@ http://purl.uniprot.org/uniprot/L7N270 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or6c1 ^@ http://purl.uniprot.org/uniprot/Q8VGJ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fkbp2 ^@ http://purl.uniprot.org/uniprot/P45878 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FKBP-type PPIase family. FKBP2 subfamily.|||Endoplasmic reticulum membrane|||Inhibited by both FK506 and rapamycin.|||Interacts with ARFGEF1/BIG1 and the C-terminal of EPB41L2.|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. http://togogenome.org/gene/10090:Scn3a ^@ http://purl.uniprot.org/uniprot/A2ASI5 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basal cell membrane|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.3/SCN3A subfamily.|||Cell membrane|||Expressed in enterochromaffin cells in both colon and small bowel (at protein level) (PubMed:29142310). Expressed in pancreatic alpha and beta cells (PubMed:25172946).|||Expressed in the hippocampus at late embryonic stages and during the first week after birth. Down-regulated after postnatal day 7.|||Heterooligomer of a large alpha subunit and 2-3 smaller beta subunits. Heterooligomer with SCN2B or SCN4B; disulfide-linked. Interacts with NEDD4L.|||May be ubiquitinated by NEDD4L; which would promote its endocytosis.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:29142310). May contribute to the regulation of serotonin/5-hydroxytryptamine release by enterochromaffin cells (PubMed:29142310). In pancreatic endocrine cells, required for both glucagon and glucose-induced insulin secretion (PubMed:25172946).|||Phosphorylation at Ser-1453 in a highly conserved cytoplasmic loop slows inactivation of the channel and reduces peak sodium currents.|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Rnf216 ^@ http://purl.uniprot.org/uniprot/P58283 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by 'Lys-63'-linked di-ubiquitin.|||Auto-ubiquitinated.|||Cytoplasm|||Deletion mutant mice are viable and grossly indistinguishable from heterozygous littermates (PubMed:30649198). However, knockout leads to infertility in male but not female mice (PubMed:30649198, PubMed:33724554). In addition, RNF216-deficiency leads to down-regulation of the gonadotropin-releasing hormone signal pathway (PubMed:37439148).|||E3 ubiquitin ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their ubiquitination. Plays a role in the regulation of antiviral responses by promoting the degradation of TRAF3, TLR4 and TLR9. In turn, down-regulates NF-kappa-B and IRF3 activation as well as beta interferon production. Participates also in the regulation of autophagy by ubiquitinating BECN1 leading to its degradation and autophagy inhibition. Plays a role in ARC-dependent synaptic plasticity by mediating ARC ubiquitination resulting in its rapid proteasomal degradation (By similarity). Plays aso an essential role in spermatogenesis and male fertility (PubMed:30649198). Mechanistically, regulates meiosis by promoting the degradation of PRKACB through the ubiquitin-mediated lysosome pathway (PubMed:33724554). Modulates the gonadotropin-releasing hormone signal pathway by affecting the stability of STAU2 that is required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite (PubMed:37439148).|||Interacts with UBE2L3 and to some extent with UBE2L6. Interacts with TRAF3, TLR3, TLR4, TLR5 and TLR9. Isoform 3/ZIN binds RIPK1.|||Phosphorylation at Ser-719 enhances acceptor ubiquitin binding and chain-type specificity towards 'Lys-63' di-ubiquitin but not di-ubiquitin with other linkage types.|||The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.|||clathrin-coated vesicle http://togogenome.org/gene/10090:Serac1 ^@ http://purl.uniprot.org/uniprot/Q3U213 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SERAC1 family.|||Endoplasmic reticulum|||Membrane|||Mitochondrion|||Plays an important role in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. May catalyze the remodeling of phosphatidylglycerol and be involved in the transacylation-acylation reaction to produce phosphatidylglycerol-36:1. May be involved in bis(monoacylglycerol)phosphate biosynthetic pathway (By similarity).|||Testis. http://togogenome.org/gene/10090:Vmn2r95 ^@ http://purl.uniprot.org/uniprot/A0A338P6T0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Osbpl6 ^@ http://purl.uniprot.org/uniprot/F8WIZ7|||http://purl.uniprot.org/uniprot/Q8BXR9 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OSBP family.|||By acetylated low-density lipoprotein and dietary intake of cholesterols.|||Cell membrane|||Detected in the brain at 18.5 days post coitum (dpc), with expression increasing till it reaches its peak expression at 28 dpc.|||Endoplasmic reticulum membrane|||Endosome membrane|||Expressed in skin, respiratory epithelium, small intestine epithelium, pancreas, striated muscle, brain, spinal ganglia, and nervous plexus of the intestine (at protein level) (PubMed:14593528, PubMed:30028970). In the brain, specifically in the cerebellum, it is expressed in Purkinje and granule cells (PubMed:30028970). Expressed in hepatocytes and macrophages (PubMed:26941018).|||Homodimer (PubMed:30028970). Interacts with OSBPL3 (PubMed:30028970).|||Nucleus envelope|||Regulates cellular transport and efflux of cholesterol (By similarity). Plays a role in phosphatidylinositol-4-phophate (PI4P) turnover at the neuronal membrane (PubMed:30028970). Binds via its PH domain PI4P, phosphatidylinositol-4,5-diphosphate, phosphatidylinositol-3,4,5-triphosphate, and phosphatidic acid (PubMed:30028970). Weakly binds 25-hydroxycholesterol (By similarity).|||cytosol http://togogenome.org/gene/10090:Copb1 ^@ http://purl.uniprot.org/uniprot/Q9JIF7 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brefeldin A induces dissociation from the Golgi of the beta-COP and presumably the other coatomer subunits.|||COPI-coated vesicle membrane|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum-Golgi intermediate compartment|||Golgi apparatus membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits (By similarity). Interacts with CAPN8. Interacts with SCYL1 and PRKCE (By similarity). Interacts with COPG1 (By similarity). Interacts with ARF1 (myristoylated); this interaction is required for binding of COPB1 to Golgi membranes (By similarity). Interacts (via trunk domain) with ARF1 (via switch I region); the interaction is direct (By similarity). Interacts with KCNK2 (via N-terminus); this interaction increases the channel-mediated whole cell currents and promotes plasma membrane expression of KCNK2 (By similarity). Interacts with STX17 (By similarity). Interacts with TMEM115 (By similarity). Interacts with TMEM41B (By similarity).|||Predominantly expressed in the upper one-third of the oxyntic mucosa and in most regions of the pyloric mucosa (PubMed:16476741). Ubiquitously expressed including platelet, liver, heart, spleen, lung and kidney (PubMed:11441537).|||Proteolytically cleaved between Ser-528 and Ser-529 by CAPN8.|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. Involved in the Golgi disassembly and reassembly processes during cell cycle. Involved in autophagy by playing a role in early endosome function. Plays a role in organellar compartmentalization of secretory compartments including endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), Golgi, trans-Golgi network (TGN) and recycling endosomes, and in biosynthetic transport of CAV1 (By similarity). Plays a functional role in facilitating the transport of kappa-type opioid receptor mRNAs into axons and enhances translation of these proteins in cortical neurons. Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte triglyceride lipase (PNPLA2) with the lipid droplet surface to mediate lipolysis. http://togogenome.org/gene/10090:Lyzl4 ^@ http://purl.uniprot.org/uniprot/Q78ID0|||http://purl.uniprot.org/uniprot/Q9D925 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the glycosyl hydrolase 22 family, Gly-72 is present instead of the conserved Asp which is an active site residue. It is therefore expected that this protein lacks hydrolase activity.|||Belongs to the glycosyl hydrolase 22 family.|||Expressed strongly in testis and in epididymis, and weakly in brain and lung (PubMed:21444326, PubMed:24013621). Detected in sperm (at protein level) (PubMed:21444326).|||May be involved in fertilization (PubMed:21444326). Has no detectable bacteriolytic in vitro (PubMed:21444326). Has no lysozyme activity in vitro (By similarity).|||Monomer.|||No expression in the testis of 2-weeks-old neonates, the expression reaches a peak level at 12 weeks. After that, the level gradually decreases as the age increases (PubMed:21444326, PubMed:24013621).|||Secreted|||acrosome|||flagellum http://togogenome.org/gene/10090:Rplp1 ^@ http://purl.uniprot.org/uniprot/P47955|||http://purl.uniprot.org/uniprot/Q58E35 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the eukaryotic ribosomal protein P1/P2 family.|||Heterodimer with RPLP2 at the lateral ribosomal stalk of the large ribosomal subunit.|||Plays an important role in the elongation step of protein synthesis.|||Ubiquitinated at Lys-92 and Lys-93 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling). http://togogenome.org/gene/10090:Exosc4 ^@ http://purl.uniprot.org/uniprot/Q921I9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase PH family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure (By similarity). Interacts with DDX60 (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC4 binds to ARE-containing RNAs (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Cdyl2 ^@ http://purl.uniprot.org/uniprot/Q9D5D8 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts (via chromo domain) with histone H3K9me3.|||Nucleus http://togogenome.org/gene/10090:Or7g28 ^@ http://purl.uniprot.org/uniprot/Q8VET8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pkm ^@ http://purl.uniprot.org/uniprot/P52480 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-433 by EP300, leading to impair phosphoenolpyruvate substrate-binding and promote its homodimerization and subsequent translocation to the nucleus. Deacetylation at Lys-433 by SIRT6 promotes its nuclear export into the cytoplasm, leading to suppress its nuclear localization and oncogenic function.|||Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.|||Belongs to the pyruvate kinase family.|||Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.|||Cytoplasm|||Embryonic stem cells and embryonal carcinoma cells.|||FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35.|||Has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity.|||ISGylated.|||Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2. Acetylation at Lys-433 promotes its translocation into the nucleus and homodimerization, promoting the protein kinase activity.|||Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (By similarity). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (By similarity). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (By similarity). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (By similarity). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (By similarity). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (PubMed:29996098). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (PubMed:28575669). Plays a role in caspase independent cell death of tumor cells (By similarity).|||Monomer and homotetramer; exists as a monomer in the absence of D-fructose 1,6-bisphosphate (FBP), and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds 3,3',5-triiodo-L-thyronine (T3). Tetramer formation induces pyruvate kinase activity. The tetrameric form has high affinity for the substrate and is associated within the glycolytic enzyme complex. FBP stimulates the formation of tetramers from dimers. Homodimer; exists in a dimeric form in tumor cells and the dimeric form has less affinity for the phosphoenolpyruvate substrate. The homodimer converts into a protein kinase. Interacts with HERC1, POU5F1 and PML. Interacts with EGLN3; the interaction hydroxylates PKM under hypoxia and enhances binding to HIF1A. Interacts with HIF1A; the interaction is enhanced by binding of EGLN3, promoting enhanced transcription activity under hypoxia. Interacts with TRIM35; this interaction prevents FGFR1-dependent tyrosine phosphorylation. Interacts with JMJD8. Interacts with TRAF4. Interacts with (phosphorylated) CTNNB1; leading to activate transcription. Interacts with TSC22D2; the interaction results in reduced nuclear levels of PKM isoform M2, leading to repression of cyclin CCND1 transcription and reduced cell growth (By similarity).|||Myeloid-cell-specific BMAL1 and PKM2 double knockout reduces the risk of sepsis lethality which is associated with reduced serum lactate levels and reduced CD274 expression in macrophages.|||Nucleus|||Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth. In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity.|||There are 4 isozymes of pyruvate kinase in mammals (L, R, M1, M2) encoded by 2 different genes: PKLR and PKM. The L and R isozymes are generated from the PKLR by differential splicing of RNA; the M1 and M2 forms are produced from the PKM gene by differential splicing. L type is major isozyme in the liver, R is found in red cells, M1 is the main form in muscle, heart and brain, and M2 is found in early fetal tissues as well as in most cancer cells.|||Under hypoxia, hydroxylated by EGLN3. http://togogenome.org/gene/10090:Zfp608 ^@ http://purl.uniprot.org/uniprot/Q56A10 ^@ Function|||Tissue Specificity ^@ Expressed at low levels in thymocytes.|||Transcription factor, which represses ZNF609 transcription. http://togogenome.org/gene/10090:Sprr2f ^@ http://purl.uniprot.org/uniprot/O70557 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane (By similarity).|||Cytoplasm|||Expressed in uterus.|||Expression in uterus varies during the estrous cycle, with highest levels during proestrus and estrus stages and declining sharply from metestrus to diestrus. During early pregnancy, uterine expression is markedly increased at 1 dpc, declines rapidly at 2 dpc and is almost undetectable from 3 dpc to 6 dpc.|||Up-regulated by estrogen in the uterus of ovariectomized animals, with strongly increased expression detected in luminal epithelial and stromal cells at 6 and 12 hours after hormone injection. http://togogenome.org/gene/10090:Zbtb17 ^@ http://purl.uniprot.org/uniprot/Q60821 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed ubiquitously from early embryogenesis (6.5 dpc) to organogenesis, predominantly in neural and epithelial tissues.|||Found in all the embryonic and adult tissues examined.|||Homooligomerizes (via the BTB/POZ domain), multimerization is required for DNA binding. Binds to the C-terminal helix-loop-helix motif of MYC which inhibits ZBTB17 transactivation and growth arrest activities and renders it insoluble in the nucleus. Also interacts with HCFC1, MAGEA4 and TMPRSS11A. Interacts (via the C-terminal zinc fingers) with GFI1; the interaction results in the recruitment of MYC to the CDKN1A/p21 and CDKN1B promoters and repression of transcription. Interacts with TRAF2, interfering with the binding of UBC13 to TRAF2, and inhibiting TRAF2 E3 ligase activity. Interacts with BCL6; the interaction inhibits ZBTB17 transactivation activity on target genes involved in cell cycle arrest. Interacts with ZBTB49; this interaction blocks ZBTB17-mediated repression of RB1 (By similarity).|||Mice produce inviable embryos which are severely retarded in early development and do not undergo normal gastrulation due to massive apoptosis of ectodermal cells around day 7.5.|||Nucleus|||Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation. Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment. Represses RB1 transcription; this repression can be blocked by interaction with ZBTB49 (By similarity).|||Undergoes 'Lys-48'-linked polyubiquitination at Lys-388 and Lys-472 and subsequent proteasomal degradation in a TRAF2-dependent manner and upon TNFA stimulation. http://togogenome.org/gene/10090:Clps ^@ http://purl.uniprot.org/uniprot/Q9CQC2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the colipase family.|||Colipase is a cofactor of pancreatic lipase. It allows the lipase to anchor itself to the lipid-water interface. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase.|||Enterostatin has a biological activity as a satiety signal.|||Expressed by the pancreas.|||Forms a 1:1 stoichiometric complex with pancreatic lipase.|||Secreted http://togogenome.org/gene/10090:Fam81a ^@ http://purl.uniprot.org/uniprot/Q3UXZ6 ^@ Similarity ^@ Belongs to the FAM81 family. http://togogenome.org/gene/10090:Or2d2 ^@ http://purl.uniprot.org/uniprot/Q8VG49 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Clock ^@ http://purl.uniprot.org/uniprot/O08785 ^@ Domain|||Function|||Induction|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (PubMed:11779462). Forms a heterodimer with BMAL1 (PubMed:9616112, PubMed:12897057, PubMed:16717091, PubMed:16980631, PubMed:18662546, PubMed:19946213, PubMed:22653727). The CLOCK-BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and for phosphorylation of both CLOCK and BMAL1 (PubMed:12897057). Interacts with NR3C1 in a ligand-dependent fashion (PubMed:19141540). Interacts with ESR1 and estrogen stimulates this interaction (By similarity). Interacts with the complex p35/CDK5 (PubMed:24235147). Interacts with RELA/p65 (PubMed:22895791). Interacts with KAT2B, CREBBP and EP300 (By similarity). Interacts with ID1 and ID3 (PubMed:20861012). Interacts with ID2 (PubMed:20861012). Interacts with MTA1 (PubMed:24089055). Interacts with OGA (PubMed:23395175). Interacts with SIRT1 (PubMed:18662546, PubMed:18662547). Interacts with CIPC (PubMed:17310242). Interacts with EZH2 (PubMed:16717091). Interacts with EIF4E, PIWIL1 and DDX4 (PubMed:22900038). Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a translocation to the nucleus (PubMed:16717091, PubMed:18430226, PubMed:18662546). Interaction of the CLOCK-BMAL1 heterodimer with PER or CRY inhibits transcription activation. Interaction of the CLOCK-BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (By similarity). The CLOCK-BMAL1 heterodimer interacts with GSK3B (PubMed:19946213). Interacts with KDM5A (PubMed:21960634). Interacts with KMT2A; in a circadian manner (PubMed:21113167). Interacts with MYBBP1A (PubMed:19129230). Interacts with THRAP3 (PubMed:24043798). Interacts with MED1; this interaction requires the presence of THRAP3 (PubMed:24043798). Interacts with NCOA2 (PubMed:24529706). The CLOCK-BMAL1 heterodimer interacts with PASD1. Interacts with NDUFA9. Interacts with IMPDH2; in a circadian manner (By similarity). Interacts with ASS1; in a circadian manner (PubMed:28985504). Interacts with PIWIL2 (via PIWI domain) (PubMed:28903391). Interacts with HNF4A (By similarity).|||Contains a Gln-rich C-terminal domain which could correspond to the transactivation domain.|||Cytoplasm|||Expressed equally in brain, eye, testes, ovaries, liver, heart, lung, kidney. In the brain, expression is abundant in the suprachiasmatic nuclei (SCN), in the pyriform cortex, and in the hippocampus. Low expression throughout the rest of the brain. Expression does not appear to undergo circadian oscillations.|||In the SCN, nuclear expression is lowest between CT7 and CT13. Cytoplasmic expression is highest at these times. In liver, peak levels from CT21 to CT3. Expression of both phosphorylated and unphosphorylated forms of BMAL1 with other circadian clock proteins occurs between CT15 and CT18. Expression in the heart oscillates in a circadian manner.|||Nucleus|||O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-BMAL1 heterodimer thereby increasing CLOCK-BMAL1-mediated transcriptional activation of PER1/2/3 and CRY1/2.|||Phosphorylation is dependent on the CLOCK-BMAL1 heterodimer formation. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver: the hyperphosphorylated form peaks at midnight (CT18), while the hypophosphorylated form is abundant throughout the day. May be phosphorylated by CSNK1D and CKSN1E.|||Sumoylation enhances its transcriptional activity and interaction with ESR1, resulting in up-regulation of ESR1 activity. Estrogen stimulates sumoylation. Desumoylation by SENP1 negatively regulates its transcriptional activity.|||The naturally-occurring CLOCK variant, missing exon 19 (deletion of AA 514-564) due to an A-->T nucleotide transversion in a splice donor site, forms a heterodimer with DNA, but fails to activate transcription. Homozygous CLOCK mutants have a circadian rhythm that is increased from 3 to 4 hours and usually the circadian rhythmicity is lost at constant darkness. Expression of CLOCK is also reduced. There also exists an alternative spliced CLOCK variant missing both exon 18 and exon 19 (AA 484-564).|||Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. May play a role in spermatogenesis; contributes to the chromatoid body assembly and physiology. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (By similarity). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (By similarity). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3'. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region. The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner (By similarity). Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (PubMed:30012868).|||Ubiquitinated, leading to its proteasomal degradation.|||Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.|||cytosol http://togogenome.org/gene/10090:Lrrc41 ^@ http://purl.uniprot.org/uniprot/Q8K1C9 ^@ Caution|||Domain|||Function|||Subunit ^@ It is uncertain whether Met-1 or Met-23 is the initiator.|||Part of an E3 ubiquitin-protein ligase complex with Elongin BC (ELOB and ELOC), RBX1 and CUL5. Component of a probable ECS(LRRC41) complex which contains CUL5, RNF7/RBX2, Elongin BC and LRRC41. Interacts with CUL5, RNF7, ELOB and ELOC (By similarity).|||Probable substrate recognition component of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]. http://togogenome.org/gene/10090:Gapt ^@ http://purl.uniprot.org/uniprot/Q8CB93 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GAPT family.|||Cell membrane|||Expressed primarily in B220+ splenocytes and total bone marrow cells. Expressed at lower levels in mast cells and dendritic cells. Not detected in T-cells and macrophages (at protein level).|||Interacts with GRB2.|||Mice are normal in appearance, size and fertility. In aged mice, the number of MZ B-cells is increased, and serum concentrations of IgM, IgG2b, and IgG3 are elevated.|||Negatively regulates B-cell proliferation following stimulation through the B-cell receptor. May play an important role in maintenance of marginal zone (MZ) B-cells. http://togogenome.org/gene/10090:Bpifa3 ^@ http://purl.uniprot.org/uniprot/Q9D9J8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BPI/LBP/Plunc superfamily. Plunc family.|||Secreted http://togogenome.org/gene/10090:Diaph2 ^@ http://purl.uniprot.org/uniprot/K4PWM5|||http://purl.uniprot.org/uniprot/O70566|||http://purl.uniprot.org/uniprot/Q6W4W7 ^@ Developmental Stage|||Domain|||Function|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the formin homology family. Diaphanous subfamily.|||Expressed in liver, heart, kidney, ovary and testis, at 16 dpc, P6 and P16.|||Interacts with MAPRE1 and APC.|||May be involved in oogenesis.|||Probable cloning artifact.|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity). http://togogenome.org/gene/10090:Doc2g ^@ http://purl.uniprot.org/uniprot/Q9ESN1 ^@ Function ^@ May be involved in regulation of vesicular trafficking. In vitro, does not bind calcium and phospholipids. http://togogenome.org/gene/10090:Or2a5 ^@ http://purl.uniprot.org/uniprot/Q8VES9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxo3 ^@ http://purl.uniprot.org/uniprot/Q9DC63 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex SCF(FBXO3) consisting of FBXO3, SKP1, CUL1 and RBX1. Interacts with PML, interaction is direct and takes place either alone or within the SCF complex.|||Substrate recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex, SCF(FBXO3), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome (By similarity). In the presence of PML, HIPK2 ubiquitination still occurs, but degradation is prevented (By similarity). PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation (By similarity). The SCF(FBXO3) also acts as a regulator of inflammation by mediating ubiquitination and degradation of FBXL2: specifically recognizes FBXL2 phosphorylated at 'Thr-404' and promotes its ubiquitination (PubMed:23542741). http://togogenome.org/gene/10090:Odad3 ^@ http://purl.uniprot.org/uniprot/Q8BSN3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ At 7.5 dpc specifically expressed in the ventral node.|||Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Involved in mediating assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity). May be required for motile cilia function (PubMed:24067530).|||Component of the outer dynein arm-docking complex along with ODAD1, ODAD2, ODAD4 and CLXN (By similarity). Interacts with ODAD1 (By similarity). Interacts with PIERCE1 and PIERCE2; the interactions link the outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme (By similarity).|||Mice have a spectrum of laterality defects, including complex congenital heart defects associated with heterotaxy, and airway epithelia show largely immotile cilia with loss of the outer dynein arms.|||centriole|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Ngf ^@ http://purl.uniprot.org/uniprot/P01139|||http://purl.uniprot.org/uniprot/Q6LDU8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NGF-beta family.|||Detected in submaxillary gland (at protein level) (PubMed:1284621). Highly expressed in male submaxillary gland. Levels are much lower in female submaxillary gland (PubMed:6336309, PubMed:1284621).|||Endosome lumen|||Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain.|||Homodimer (PubMed:1956407, PubMed:8201620, PubMed:20036257, PubMed:22649032, PubMed:26144237, PubMed:30061605). The homodimer interacts with a single NTRK1 chain (PubMed:22649032). The homodimer interacts with a single NGFR chain (By similarity). The NGF dimer interacts with a single SORCS2 chain (via extracellular domain) (PubMed:30061605). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis (PubMed:20036257). Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains) (PubMed:22155786, PubMed:30061605). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF (PubMed:24908487). The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF (PubMed:20036257). Interacts with ADAM10 in a divalent cation-dependent manner (By similarity).|||Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:20036257). Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (PubMed:22649032). The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse (PubMed:22155786). In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (PubMed:20036257). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (By similarity). Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer (PubMed:22649032, PubMed:26144237). The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (PubMed:22649032).|||Secreted http://togogenome.org/gene/10090:Krt39 ^@ http://purl.uniprot.org/uniprot/Q6IFX4 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||May play a role in late hair differentiation.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Or4c31 ^@ http://purl.uniprot.org/uniprot/Q8VFF8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ube2o ^@ http://purl.uniprot.org/uniprot/Q6ZPJ3 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-conjugating enzyme family.|||By EPO/Erythropoietin which induces erythroid differentiation.|||Cytoplasm|||E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins. Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity. Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis. Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location. Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly.|||Highly expressed in reticulocytes.|||Inhibited by inorganic arsenite such as phenylarsenoxides.|||Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with UBR2 (PubMed:31268597).|||Nucleus|||Phosphorylated. Phosphorylation affects subcellular location.|||Ubiquitinated: autoubiquitinates, possibly affecting its subcellular location. http://togogenome.org/gene/10090:Pabpn1l ^@ http://purl.uniprot.org/uniprot/Q5XFR0 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation ^@ Binds the poly(A) tail of mRNA.|||Cytoplasm|||Deletions and sequence errors.|||Expression is restricted to oogenesis, early embryogenesis and the adult ovary. http://togogenome.org/gene/10090:Prcp ^@ http://purl.uniprot.org/uniprot/Q7TMR0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S28 family.|||Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH (By similarity).|||Homodimer.|||Lysosome http://togogenome.org/gene/10090:Gtf2f1 ^@ http://purl.uniprot.org/uniprot/Q3THK3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIF alpha subunit family.|||Heterodimer of an alpha and a beta subunit. Interacts with GTF2F2, CTDP1, TAF6/TAFII80 and URI1 (By similarity). Interacts with GTF2B (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2 (By similarity).|||Nucleus|||Phosphorylated on Ser and other residues by TAF1 and casein kinase II-like kinases.|||TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation (By similarity). http://togogenome.org/gene/10090:Ring1 ^@ http://purl.uniprot.org/uniprot/O35730 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of chromatin-associated Polycomb (PcG) complexes. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2/RING2 MBLR, L3MBTL2 and YAF2. Interacts with CBX2 and PCGF6. Component of a PRC1-like complex. Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RNF2/RING2. Interacts with PHC2, PCGF2, RNF2; CBX6, CBX7 and CBX8. Interacts with BMI1 (By similarity). Interacts with MN1 (By similarity). Interacts with USP26.|||Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity (By similarity).|||Expressed in cells of the central nervous system (CNS) from 8.5 to 11.5 dpc. Expressed in the hindbrain (in the rhombomere boundaries) at 10.5 dpc. Expressed in CNS (ventricular zone and spinal cord), peripheral nervous system (PNS, sensory cranial and spinal ganglia), olfactory and tongue epithelia at 13.5 dpc. Expressed in CNS, thymus, various epithelial cell types including the olfactory, tooth and tongue epithelia at 15.5 dpc.|||Nucleus speckle http://togogenome.org/gene/10090:Smok2b ^@ http://purl.uniprot.org/uniprot/Q9QYZ3 ^@ Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Smok subfamily.|||Encoded on the T-complex, a region of 20-30 Mb on proximal third of mouse chromosome 17. Naturally occurring variant forms of the T-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development.|||May play a role in sperm motility, especially in the regulation of flagellar function.|||Testis-specific. Expressed in the testis from 22 days postpartum (22 dpp). http://togogenome.org/gene/10090:Gpx4 ^@ http://purl.uniprot.org/uniprot/O70325|||http://purl.uniprot.org/uniprot/Q76LV0 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutathione peroxidase family.|||Cytoplasm|||Embryonic lethality in utero at midgestation, caused by inability to initiate gastrulation and the absence of embryonic cavities (PubMed:12745070). Conditional knockout mice lacking Gpx4 in spermatocytes causes sperm abnormalities and male infertility (PubMed:19783653). Conditional knockout mice lacking Gpx4 in photoreceptor cells causes retinal degeneration, decreased mitochondrial biomass and decreased number of connecting cilia in these cells (PubMed:22207760). Mice display neurodegeneration (PubMed:18762024). Conditional knockout mice lacking Gpx4 in neurons show reduced parvalbumin-positive interneurons and develop phenotypes, such as cerebellar hypoplasia and seizures (PubMed:19890015, PubMed:24599700). Induced disruption of Gpx4 in mice causes acute renal failure and early death due to ferroptosis (PubMed:25402683).|||Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (PubMed:29290465). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (PubMed:12566075). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:12566075, PubMed:24439385, PubMed:25402683, PubMed:25922076, PubMed:29290465). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (PubMed:29290465). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (PubMed:29290465). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (PubMed:12566075). Required for normal sperm development and male fertility (PubMed:19783653, PubMed:25922076). Essential for maturation and survival of photoreceptor cells (PubMed:22207760). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (PubMed:25824823). Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism (By similarity). Reduces hydroperoxy ester lipids formed by a 15-lipoxygenase that may play a role as down-regulator of the cellular 15-lipoxygenase pathway (By similarity).|||Highly expressed during embryogenesis (PubMed:1668477). Down-regulated between 14.5 dpc and 17.5 dpc (PubMed:1668477).|||Highly expressed during embryogenesis (PubMed:1668477). In contrast to isoform Mitochondrial and isoform Nuclear, which are down-regulated between 14.5 dpc and 17.5 dpc, remains constant (PubMed:1668477).|||Isoform mitochondrial: Selective disruption of isoform mitochondrial causes sperm abnormalities and male infertility (PubMed:19417079).|||Mainly expressed in sperm (PubMed:11344099). Weakly expressed during embryogenesis (PubMed:1668477). Down-regulated between 14.5 dpc and 17.5 dpc (PubMed:1668477).|||Mitochondrion|||Monomer. Has a tendency to form higher mass oligomers.|||Nucleus|||Produced by alternative initiation at Met-28 of isoform Mitochondrial.|||Required for male fertility by stabilizing the condensed chromatin in sperm nuclei (PubMed:12566075).|||Specifically able to suppress the production of leukotriene and prostaglandin in response to several stimuli by reducing fatty acid hydroperoxide.|||Specifically required to prevent mitochondrial cell death by mediating reduction of cardiolipin hydroperoxide (By similarity). Also required for normal sperm development and male fertility (PubMed:19417079).|||The presence of selenolate in the active site is essential for resistance to overoxidation: in the absence of reducing equivalents, the enzyme can form a selenylamide intermediate during its catalytic cycle, thereby preventing its irreversible overoxidation.|||Widely expressed with the highest levels in testis, heart, cerebrum, ileum, stomach, liver, jejunum and epididymis (PubMed:17503194). Expressed primarily in testis and sperm midpiece (at protein level) (PubMed:19417079, PubMed:12566075). Expressed in brain (at protein level) (PubMed:22207760, PubMed:12566075). Expressed in heart, liver and kidney (at protein level) (PubMed:12566075). Expressed in retina, especially in inner segments of photoreceptor cells (at protein level) (PubMed:22207760). http://togogenome.org/gene/10090:Gpr33 ^@ http://purl.uniprot.org/uniprot/D8VER2|||http://purl.uniprot.org/uniprot/O88416 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the chemokine-like receptor (CMKLR) family.|||Cell membrane|||Expressed predominantly in lung, spleen and testis.|||Membrane|||Orphan receptor; could be a chemoattractant receptor. http://togogenome.org/gene/10090:Chsy1 ^@ http://purl.uniprot.org/uniprot/Q6ZQ11 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Divalent metal cations. Highest activities are measured with Co(2+), Mn(2+) and Cd(2+).|||Golgi stack membrane|||Has both beta-1,3-glucuronic acid and beta-1,4-N-acetylgalactosamine transferase activity. Transfers glucuronic acid (GlcUA) from UDP-GlcUA and N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of the elongating chondroitin polymer. Involved in the negative control of osteogenesis likely through the modulation of NOTCH signaling.|||Secreted http://togogenome.org/gene/10090:Ddc ^@ http://purl.uniprot.org/uniprot/O88533|||http://purl.uniprot.org/uniprot/Q5SUV8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the group II decarboxylase family.|||Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine and L-5-hydroxytryptophan to serotonin.|||Homodimer. http://togogenome.org/gene/10090:Nfyb ^@ http://purl.uniprot.org/uniprot/P63139|||http://purl.uniprot.org/uniprot/Q8C590 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NFYB/HAP3 subunit family.|||Can be divided into 3 domains: the weakly conserved A domain, the highly conserved B domain thought to be involved in subunit interaction and DNA binding, and the Glu-rich C domain.|||Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.|||Heterotrimeric transcription factor composed of three components, NF-YA, NF-YB and NF-YC. NF-YB and NF-YC must interact and dimerize for NF-YA association and DNA binding. Interacts with C1QBP (By similarity).|||Heterotrimeric transcription factor composed of three components, NF-YA, NF-YB and NF-YC. NF-YB and NF-YC must interact and dimerize for NF-YA association and DNA binding. Interacts with C1QBP.|||Monoubiquitination at Lys-140 plays an important role in transcriptional activation by allowing the deposition of histone H3 methylations as well as histone H2B monoubiquitination at 'Lys-121'.|||Nucleus http://togogenome.org/gene/10090:Smim12 ^@ http://purl.uniprot.org/uniprot/Q78RX3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMIM12 family.|||Membrane http://togogenome.org/gene/10090:Snap29 ^@ http://purl.uniprot.org/uniprot/Q9ERB0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNAP-25 family.|||Cytoplasm|||Forms a SNARE complex, composed of VAMP8, SNAP29 and STX17, involved in fusion of autophagosome with lysosome (By similarity). Interacts with multiple syntaxins including STX6 (By similarity). Interacts with EIPR1 (By similarity). Interacts with STX17; this interaction is increased in the absence of TMEM39A (By similarity).|||Golgi apparatus membrane|||SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions.|||autophagosome membrane|||cilium membrane http://togogenome.org/gene/10090:Ggps1 ^@ http://purl.uniprot.org/uniprot/Q3V0T8|||http://purl.uniprot.org/uniprot/Q9WTN0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FPP/GGPP synthase family.|||Binds 2 Mg(2+) ions per subunit.|||Catalyzes the trans-addition of the three molecules of isopentenyl diphosphate (IPP) onto dimethylallyl pyrophosphate (DMAPP) to form geranylgeranyl pyrophosphate, an important precursor of carotenoids and geranylated proteins.|||Cytoplasm|||Homohexamer; trimer of homodimers.|||Z line|||perinuclear region http://togogenome.org/gene/10090:Psmd11 ^@ http://purl.uniprot.org/uniprot/Q3UWW9|||http://purl.uniprot.org/uniprot/Q5BKQ9|||http://purl.uniprot.org/uniprot/Q8BG32 ^@ Function|||Similarity|||Subunit ^@ Belongs to the proteasome subunit S9 family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD11, a base containing 6 ATPases and few additional components.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity. http://togogenome.org/gene/10090:Tedc1 ^@ http://purl.uniprot.org/uniprot/Q3UK37 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a positive regulator of ciliary hedgehog signaling. Required for centriole stability (PubMed:29459677). May play a role in counteracting perturbation of actin filaments, such as after treatment with the actin depolymerizing microbial metabolite Chivosazole F (By similarity).|||Interacts with TEDC2 (PubMed:29459677). Found in a complex with TEDC1, TEDC2, TUBE1 and TUBD1 (PubMed:29459677).|||centriole|||cilium http://togogenome.org/gene/10090:Sned1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0N0|||http://purl.uniprot.org/uniprot/Q70E20 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Early neonatal lethality, possibly due to impaired nasal respiration caused by asymmetric and occluded nasal cavities (PubMed:33012048). In addition to nasal cavity occlusion, mice display growth defects and craniofacial malformations (PubMed:33012048). Mice with a specific deletion in neural crest-cells survive, but display growth defects and craniofacial malformations partly phenocopying the effect of the global knockout mice (PubMed:33012048).|||Expressed in lung.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Phosphorylated on serine and threonine residues.|||Widely expressed in embryos, notably in skeletal and craniofacial precursors (PubMed:33012048). Expressed in mesenchymal cells or stromal cell from 10.5 dpc to 17.5 dpc (PubMed:15162516).|||extracellular matrix http://togogenome.org/gene/10090:Pramel42 ^@ http://purl.uniprot.org/uniprot/J3QK78 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Cdkn3 ^@ http://purl.uniprot.org/uniprot/Q810P3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family.|||Interacts with cyclin-dependent kinases such as CDK1, CDK2 and CDK3. Does not interact with CDK4. Interacts (via C-terminus) with phosphorylated CDK2 (via C-terminal helix). Interacts with MS4A3 (via C-terminus); the interaction enhances CDKN3 enzymatic activity (By similarity).|||May play a role in cell cycle regulation. Dual specificity phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues. Dephosphorylates CDK2 at 'Thr-160' in a cyclin-dependent manner (By similarity).|||Probable cloning artifact.|||perinuclear region http://togogenome.org/gene/10090:Cd96 ^@ http://purl.uniprot.org/uniprot/Q3U0X8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked. Interacts with PVR (By similarity).|||May be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response. Promotes NK cell-target adhesion by interacting with PVR present on target cells. May function at a time after T and NK cells have penetrated the endothelium using integrins and selectins, when they are actively engaging diseased cells and moving within areas of inflammation (By similarity).|||Membrane http://togogenome.org/gene/10090:Cenpo ^@ http://purl.uniprot.org/uniprot/Q8K015 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-O/MCM21 family.|||Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Modulates the kinetochore-bound levels of NDC80 complex (By similarity).|||Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (By similarity).|||Nucleus|||centromere|||kinetochore http://togogenome.org/gene/10090:Zfhx2 ^@ http://purl.uniprot.org/uniprot/Q2MHN3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected at 11.5 days post coitum (dpc) in developing brain, and continues to be expressed all the way through to postnatal day 21 (PubMed:23300874). In brain, expressed at 13.5 dpc in thalamus, hypothalamus, midbrain and pontine area (PubMed:16257534).|||Expressed in brain (at protein level) (PubMed:23300874). Expressed at the highest levels in the pyramidal cell layer of the hippocampus, the suprachiasmatic nucleus, laterodorsal thalamic nucleus, lateral geniculate nucleus, substantia nigra pars compacta, and magnocellular part of the red nucleus (at protein level) (PubMed:23300874). Highly expressed in dorsal root ganglia (PubMed:29253101). Expressed at lower levels in kidney, stomach, liver, heart and testis (PubMed:16257534, PubMed:23300874).|||Expression in specific regions of the developing brain is negatively regulated by its antisense mRNA. In particular, down-regulated in pyramidal and granule cells in the hippocampus during early differentiation and the migration stage.|||Knockout mice exhibit a range of subtle behavioral abnormalities. Locomotor activity is generally increased, but only in familiar environments. There is a slight increase in depression-like behavior, most notably increased immobility in the tail suspension test. Assays of anxiety-like behavior give conflicting results; the open field test indicates a slight reduction in anxiety-like behavior whereas other tests show no significant behavioral changes (PubMed:23300874). Knockout mice are hyposensitive to noxious mechanical stimuli applied to the tail and hypersensitive to noxious heat (PubMed:29253101).|||Nucleus|||Transcriptional regulator that is critical for the regulation of pain perception and processing of noxious stimuli. http://togogenome.org/gene/10090:Sugp2 ^@ http://purl.uniprot.org/uniprot/Q8CH09 ^@ Function|||Subcellular Location Annotation ^@ May play a role in mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Fbxo36 ^@ http://purl.uniprot.org/uniprot/Q9CQ24 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Or4g16 ^@ http://purl.uniprot.org/uniprot/Q8VF38 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sfmbt2 ^@ http://purl.uniprot.org/uniprot/Q3UH07|||http://purl.uniprot.org/uniprot/Q3UH63 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Afm ^@ http://purl.uniprot.org/uniprot/O89020 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ALB/AFP/VDB family.|||Contaminating sequence.|||Detected in brain, especially on brain capillaries (at protein level). Expressed in isolated brain capillaries.|||Forms a 1:1 complex with Wnt family members; interacts with WNT1, WNT2B, WNT3, WNT5A, WNT7A, WNT7B, WNT8, WNT9A, WNT9B, WNT10A and WNT10B (By similarity). Interacts with WNT3A (PubMed:26902720).|||Functions as carrier for hydrophobic molecules in body fluids. Essential for the solubility and activity of lipidated Wnt family members, including WNT1, WNT2B, WNT3, WNT3A, WNT5A, WNT7A, WNT7B, WNT8, WNT9A, WNT9B, WNT10A and WNT10B. Binds vitamin E. May transport vitamin E in body fluids under conditions where the lipoprotein system is not sufficient. May be involved in the transport of vitamin E across the blood-brain barrier.|||N-glycosylated; more than 90% of the glycans are sialylated.|||Secreted|||The second albumin domain forms a deep binding pocket that contains palmitoleic acid (in vitro). Palmitoleic acid is most likely not the physiological ligand. Instead, this pocket may accomodate the covalently bound lipid moiety of Wnt family members. http://togogenome.org/gene/10090:Mypn ^@ http://purl.uniprot.org/uniprot/Q5DTJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the myotilin/palladin family.|||Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.|||Cytoplasm|||Interacts with TTN/titin, NEB, NEBL, ACTN2 and CARP.|||Nucleus|||Z line|||sarcomere http://togogenome.org/gene/10090:Abca7 ^@ http://purl.uniprot.org/uniprot/E9Q6G4|||http://purl.uniprot.org/uniprot/Q91V24 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ According to one study, knockout mice are not viable and heterozygous knockout mice display impaired phagocytosis of apoptotic cells (PubMed:16908670). However, another study shows that knockout mice are viable and females have less visceral fat and lower total serum and high density lipoprotein cholesterol level (PubMed:15550377). Knockout mice exhibit altered lipid profile in mouse brains, compromised spatial memory and increased BACE1 activity (PubMed:27030769). Display an increase in amyloid-beta protein 42 (Abeta42) from 4 to 24 weeks of age, whereas amyloid-beta protein 40 (Abeta40) is increased at 4 weeks and decreased at 24 weeks of age (PubMed:26260791). Increased endocytotic uptake of APP into endosomes in primary microglia cells (PubMed:26260791). Reduced phagocytic uptake of Abeta42 and Abeta40 by microglia cells and phagocytes (PubMed:27472885). Decreased macrophage phagocytosis in the peritoneal cavity (PubMed:20495215). Decreased surface CD1D expression on double positive thymocytes, on antigen-presenting thymocytes, on peripheral antigen-presenting cells in the spleen and on peritoneal macrophages (PubMed:28091533). Increased accumulation of CD1D to late endosomes (PubMed:28091533). Impaired natural killer T (NKT) cell development with a 2-fold decrease in frequencies and total numbers of NKT cells in the thymus and a reduction of peripheral NKT cells in spleen and liver (PubMed:28091533). Reduced proliferation during early stages of NKT development and reduced expression of Egr2 in NKT cells (PubMed:28091533). Decreased number of plasma membrane lipid rafts on thymocytes and a reduction of CAV1 and CD1D clusters in macrophages (PubMed:28091533). RNAi-mediated knockdown reduces phagocytosis of apoptotic cells by macrophages (PubMed:16908670).|||Belongs to the ABC transporter superfamily. ABCA family.|||Cell membrane|||Cytoplasm|||Early endosome membrane|||Golgi apparatus membrane|||Membrane|||N-glycosylated.|||Probable ATP-binding cassette (ABC) transporter that plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:12917409, PubMed:15550377, PubMed:16908670, PubMed:27472885, PubMed:27030769, PubMed:20495215). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409). May also mediate cholesterol efflux (By similarity). May regulate cellular ceramide homeostasis during keratinocyte differentiation (By similarity). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (PubMed:28091533). Plays a role in phagocytosis of apoptotic cells by macrophages (PubMed:16908670). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (PubMed:20495215). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (PubMed:27472885). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791, PubMed:27030769).|||There are conflicting results concerning the role of ABCA7 in lipid transport. ABCA7 was described to play a role in apolipoprotein-mediated phospholipid and cholesterol efflux when expressed in HEK293 cells (PubMed:12917409, PubMed:27472885). However, another report shows that ABCA7 deficiency does not influence cholesterol and phospholipid efflux in mouse primary macrophages, but leads to lower serum HDL cholesterol levels and a reduction in fat mass in female mice (PubMed:15550377).|||Up-regulated during differentiation from monocytes to macrophages (PubMed:27472885). Down-regulated by digoxin.|||Widely expressed during embryogenesis (PubMed:11435699). Expressed in newborn mice with increasing expression from 4 to 24 weeks of age (PubMed:26260791).|||Widely expressed with higher expression in brain, lung, adrenal gland, spleen and hematopoietic tissues (at protein level) (PubMed:12917409, PubMed:15550377, PubMed:27472885). In the brain, expressed in cortex, cerebellum, hippocampus, olfactory bulb, neurons, astrocytes and microglia (at protein level) (PubMed:26260791). Also expressed in adipocytes and macrophages (at protein level) (PubMed:15550377, PubMed:27472885). Expressed in thymocytes (at protein level) (PubMed:28091533). Highly expressed in spleen and hematopoietic tissues (PubMed:11435699). Expressed in brain, lung, macrophages, microglia, oligodendrocytes and neurons (PubMed:27472885).|||phagocytic cup|||ruffle membrane http://togogenome.org/gene/10090:Itprid2 ^@ http://purl.uniprot.org/uniprot/Q922B9 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Ceacam20 ^@ http://purl.uniprot.org/uniprot/Q9D2Z1 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the immunoglobulin superfamily. CEA family.|||In intestinal epithelium, up-regulated in the presence of Gram-positive commensal gut bacteria. May also be up-regulated by interferon gamma (IFNG) and butyrate (a product of bacterial fermentation).|||Interacts (via extracellular domain) with PTPRH (via extracellular domain); the interaction dephosphorylates CEACAM20. Interacts (phosphorylated form) with SYK (via SH2 domains); the interaction further enhances CEACAM20 phosphorylation.|||Phosphorylated on tyrosine residues by SYK, SRC and FYN in vitro.|||Strongly expressed in the small intestine and colon (at protein level) (PubMed:25908210, PubMed:26195794). Minimal expression in other tissues (at protein level) (PubMed:26195794). Highly expressed in cecum, colon, ileum, jejunum, and testis, and also detected at lower levels in salivary gland and thymus (PubMed:16139472).|||Together with the tyrosine-protein kinase SYK, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response.|||microvillus membrane http://togogenome.org/gene/10090:Vmn2r110 ^@ http://purl.uniprot.org/uniprot/E9PWD5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Flvcr1 ^@ http://purl.uniprot.org/uniprot/A0A0A6YWJ7|||http://purl.uniprot.org/uniprot/B2RXV4 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the major facilitator superfamily. Feline leukemia virus subgroup C receptor (TC 2.A.1.28.1) family.|||Cell membrane|||Has a probable mitochondrial transit peptide at positions 1-38.|||Heme b transporter that mediates heme efflux from the cytoplasm to the extracellular compartment. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythropoiesis, a process in which heme synthesis intensifies. Possibly export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. The molecular mechanism of heme transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated.|||Heme transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation.|||Interacts with HPX.|||Lack definitive erythropoiesis, have craniofacial and limb deformities, and die in midgestation. Mice with FLVCR1 that is deleted neonatally develop a severe macrocytic anemia with proerythroblast maturation arrest. Mice lacking the plasma membrane isoform (Flvcr1a) but expressing Flvcr1b had normal erythropoiesis, but exhibited hemorrhages, edema, and skeletal abnormalities.|||Membrane|||Mitochondrion membrane|||N-Glycosylated. http://togogenome.org/gene/10090:Zfp692 ^@ http://purl.uniprot.org/uniprot/Q3U381 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May act as an transcriptional repressor for PCK1 gene expression, in turn may participate in the hepatic gluconeogenesis regulation through the activated AMPK signaling pathway.|||Nucleus|||Phosphorylation at Ser-469 results in loss of DNA-binding activity. http://togogenome.org/gene/10090:Bmp10 ^@ http://purl.uniprot.org/uniprot/Q9R229 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Down-regulation after 14.5 dpc is critical for cardiomyocytes to undergo normal developmental hypertrophic growth in early postnatal life.|||Homodimer; disulfide-linked (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity). Interacts with ENG (PubMed:21737454).|||In the embryo, expressed exclusively in the ventricular trabecular myocardium of the developing heart from 9.0 dpc-13.5 dpc. By 16.5 dpc-18.5 dpc, only detectable in atria. Highly expressed in the adult heart where it is found in the right atrium but not in the left atrium. Lower levels in adult liver and lung.|||Mice die in utero between 9.5 dpc and 10.5 dpc. They appear normal at 8.5 dpc-8.75 dpc but display cardiac dysgenesis at 9.0 dpc-9.5 dpc with profound hypoplastic ventricular walls and absence of ventricular trabeculae and have a significantly lower heart rate than wild type embryos. Mutants show up-regulation of Cdkn1c/p57KIP throughout the ventricular wall while levels of Mef2c and Nkx2-5 are normal at 8.5 dpc-8.75 dpc but are down-regulated at 9.25 dpc-9.5 dpc.|||Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines (By similarity).|||Secreted http://togogenome.org/gene/10090:Actr3b ^@ http://purl.uniprot.org/uniprot/Q641P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin family. ARP3 subfamily.|||Cell projection|||Interacts with the Arp2/3 complex composed of ARP2, ARP3, ARPC1B, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC.|||Plays a role in the organization of the actin cytoskeleton. May function as ATP-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. May decrease the metastatic potential of tumors (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Wfdc6a ^@ http://purl.uniprot.org/uniprot/Q3UW55 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Sncb ^@ http://purl.uniprot.org/uniprot/Q91ZZ3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the synuclein family.|||Cytoplasm|||Highly expressed in the brain.|||May be involved in neuronal plasticity.|||Phosphorylated. Phosphorylation by G-protein coupled receptor kinases (GRK) is more efficient than phosphorylation by CK1, CK2 and CaM-kinase II (By similarity).|||Simultaneous knockout of SNCA, SNCB and SNCG exhibit an age-dependent decrease in SNARE-complex assembly. Thus, synucleins are required for maintaining normal SNARE-complex assembly during aging in mice. http://togogenome.org/gene/10090:2510039O18Rik ^@ http://purl.uniprot.org/uniprot/Q91X21 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dvl2 ^@ http://purl.uniprot.org/uniprot/Q60838 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DSH family.|||Cell membrane|||Cytoplasmic vesicle|||Interacts through its PDZ domain with the C-terminal regions of VANGL1 and VANGL2. Interacts with Rac. Interacts with ARRB1; the interaction is enhanced by phosphorylation of DVL1 (By similarity). Can form large oligomers (via DIX domain). Interacts (via DIX domain) with DIXDC1 (via DIX domain). Interacts (via DEP domain) with AP2M1 and the AP-2 complex. Interacts with FAM105B/otulin. Interacts with DCDC2. Interacts (when phosphorylated) with FOXK1 and FOXK2; the interaction induces DVL2 nuclear translocation (By similarity). Interacts with MAPK15 (PubMed:25823377). Interacts with PKD1 (via extracellular domain) (PubMed:27214281). Interacts with LMBR1L (PubMed:31073040).|||Nucleus|||Phosphorylated by CSNK1D (By similarity). WNT3A induces DVL2 phosphorylation by CSNK1E and MARK kinases (By similarity).|||Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling.|||The DIX domain mediates homooligomerization.|||Ubiquitous.|||cytosol http://togogenome.org/gene/10090:Or51s1 ^@ http://purl.uniprot.org/uniprot/E9Q407 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:G2e3 ^@ http://purl.uniprot.org/uniprot/E9Q7C2|||http://purl.uniprot.org/uniprot/E9Q7E5|||http://purl.uniprot.org/uniprot/Q5RJY2 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (By similarity). Required for prevention of apoptotic death in early embryogenesis.|||Embryos die prior to implantation due to massive apoptosis resulting in blastocyst involution.|||In the developing embryo, expressed predominantly in the central nervous system and early limb bud. In the adult, highest expression in Purkinje cell bodies and cells lining the ductus deferens.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Ubiquitin ligase activity is mediated by two distinct domains, PHD-type zinc fingers 2 and 3. The use of these distinct domains may allow ubiquitination of different targets by each domain. The HECT domain is catalytically inactive and does not contribute to this activity.|||nucleolus http://togogenome.org/gene/10090:Smok3a ^@ http://purl.uniprot.org/uniprot/C0HKC8|||http://purl.uniprot.org/uniprot/C0HKC9 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Smok subfamily.|||May play a role in sperm motility, especially in the regulation of flagellar function.|||Testis-specific. Expressed in the testis from 22 days postpartum (22 dpp). http://togogenome.org/gene/10090:Slc38a1 ^@ http://purl.uniprot.org/uniprot/Q8K2P7 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Inhibited by alpha-(methylamino)isobutyric acid (MeAIB). Inhibited by lithium, potassium, choline ions, N-methylglucamine. The pH dependence has an allosteric effect on the transport.|||N-glycosylation plays an important role in the L-glutamine transport.|||Specifically expressed in brain and retina (at protein level). Also detected in spleen, small intestine and lung.|||Symporter that cotransports short-chain neutral amino acids and sodium ions from the extraccellular to the intracellular side of the cell membrane (PubMed:11325958, PubMed:17179157, PubMed:32668809, PubMed:27655909). The transport is elctrogenic, pH dependent and driven by the Na(+) electrochemical gradient (PubMed:11325958). Participates in the astroglia-derived glutamine transport into GABAergic interneurons for neurotransmitter GABA de novo synthesis (PubMed:31050701, PubMed:32668809). May also contributes to amino acid transport in placental trophoblast (By similarity). Regulates synaptic plasticity (PubMed:31050701).|||Up-regulated by BDNF. http://togogenome.org/gene/10090:Ybx1 ^@ http://purl.uniprot.org/uniprot/P62960 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YBX1 family.|||Cleaved by a 20S proteasomal protease in response to agents that damage DNA. Cleavage takes place in the absence of ubiquitination and ATP. The resulting N-terminal fragment accumulates in the nucleus (By similarity).|||Cytoplasm|||Cytoplasmic granule|||DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:8505341, PubMed:29712925). Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (By similarity). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (By similarity). Component of the CRD-mediated complex that promotes MYC mRNA stability (By similarity). Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (By similarity). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs (By similarity). Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (By similarity). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (PubMed:29712925). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (By similarity). Binds to TSC22D1 transcripts, thereby inhibiting their translation and negatively regulating TGF-beta-mediated transcription of COL1A2 (PubMed:20713358). Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7' (By similarity). Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (By similarity). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (By similarity). Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (By similarity). The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (By similarity).|||Expressed in kidney glomeruli (at protein level) (PubMed:20713358). In epidermis, expression is restricted to the cycling keratinocyte progenitors (at protein level) (PubMed:29712925). Expressed at high levels in the testis (PubMed:8505341). Present in the mRNP particles that mediate the storage and masking of mRNAs during spermiogenesis (PubMed:8505341).|||Found at very low levels at day 10 and levels increase at day 15 and persist throughout adulthood.|||Homodimer in the presence of ATP (PubMed:10318844, PubMed:8505341). Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (By similarity). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (PubMed:11162447). Interacts with IGF2BP1 and RBBP6 (By similarity). Component of cytoplasmic messenger ribonucleoprotein particles (mRNPs) (By similarity). Interacts with AKT1, MBNL1, SFRS9, SFRS12, ALYREF/THOC4, MSH2, XRCC5, WRN and NCL (By similarity). Interacts (via C-terminus) with APEX1 (via N-terminus); the interaction is increased with APEX1 acetylated at 'Lys-6' and 'Lys-7' (By similarity). Interacts with AGO1 and AGO2 (By similarity). Interacts with ANKRD2 (By similarity). Interacts with DERA (By similarity). Interacts with FMR1; this interaction occurs in association with polyribosome (PubMed:11162447). Interacts with ZBTB7B (PubMed:28784777). Interacts with HDGF. Interacts with ELAVL1; leading to ELAVL1 recruitment on C5-methylcytosine (m5C)-containing mRNAs and subsequent mRNA stability (By similarity).|||In the CSD domain, Trp-63 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring.|||Nucleus|||P-body|||Perinatal lethality (PubMed:15899865). Embryos develop normally up to embryonic day 13.5 dpc and then show progressive mortality (PubMed:15899865). Embryos display severe growth retardation caused by hypoplasia in multiple organs (PubMed:15899865). Fibroblasts show a normal rate of protein synthesis and minimal alterations in the transcriptome and proteome (PubMed:15899865). Mice show defects in the architecture of the skin characterized by markedly reduced thickness of the epidermis and delayed onset of the placodes to hair follicle transition (PubMed:29712925).|||Phosphorylated; increased by TGFB1 treatment (PubMed:20713358). Phosphorylation by PKB/AKT1 reduces interaction with cytoplasmic mRNA (By similarity). In the absence of phosphorylation the protein is retained in the cytoplasm (By similarity).|||Secreted|||Ubiquitinated by RBBP6; leading to a decrease of YBX1 transactivational ability.|||extracellular exosome http://togogenome.org/gene/10090:Btbd35f5 ^@ http://purl.uniprot.org/uniprot/Q99N64 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CUL3.|||Nucleus matrix|||Possible function in spermatogenesis. Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. http://togogenome.org/gene/10090:Mre11a ^@ http://purl.uniprot.org/uniprot/Q3URU4|||http://purl.uniprot.org/uniprot/Q61216|||http://purl.uniprot.org/uniprot/Q8BRV3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MRE11/RAD32 family.|||Chromosome|||Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN (By similarity). As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites (By similarity). Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (By similarity). Found in a complex with TERF2 (By similarity). Interacts with DCLRE1C/Artemis and DCLRE1B/Apollo (By similarity). Interacts with ATF2 (By similarity). Interacts with EXD2 (By similarity). Interacts with MRNIP (By similarity). Interacts with SAMHD1; leading to stimulate 3'-5' exonuclease activity (By similarity). Interacts (when ubiquitinated) with UBQLN4 (via its UBA domain) (By similarity). Interacts with CYREN (via XLF motif) (PubMed:30017584).|||Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation.|||Interaction with SAMHD1 stimulates the double-strand-specific 3'-5' exonuclease activity.|||Involved in DNA double-strand break repair (DSBR). Possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity. Also involved in meiotic DSB processing.|||Nucleus|||Ubiquitinated following DNA damage. Ubiquitination triggers interaction with UBQLN4, leading to MRE11 removal from chromatin and degradation by the proteasome.|||telomere http://togogenome.org/gene/10090:Cops6 ^@ http://purl.uniprot.org/uniprot/O88545|||http://purl.uniprot.org/uniprot/Q3UIT2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although related to the peptidase M67A family, it lacks the JAMM motif that probably constitutes the catalytic center and therefore it probably does not have a protease activity.|||Belongs to the peptidase M67A family. CSN6 subfamily.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 (By similarity). The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases (By similarity). CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively (By similarity). Has some glucocorticoid receptor-responsive activity (By similarity). Stabilizes COP1 through reducing COP1 auto-ubiquitination and decelerating COP1 turnover rate, hence regulates the ubiquitination of COP1 targets, including SFN (By similarity).|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS2, COPS4, COPS5, COPS7 (COPS7A or COPS7B) and COPS9 (By similarity). Interacts with the translation initiation factor EIF3S6 (By similarity). Interacts weakly with RBX1 (By similarity). Directly interacts with COP1 and 14-3-3 protein sigma/SFN (By similarity). Interacts with ERCC6 (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Slc45a4 ^@ http://purl.uniprot.org/uniprot/Q0P5V9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycoside-pentoside-hexuronide (GPH) cation symporter transporter (TC 2.A.2) family.|||Membrane|||Proton-associated sucrose transporter. May be able to transport also glucose and fructose.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Klrb1a ^@ http://purl.uniprot.org/uniprot/P27811 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in natural killer cells.|||Homodimer; disulfide-linked. Interacts with tyrosine kinase LCK (By similarity).|||Membrane|||Plays a stimulatory role on natural killer (NK) cell cytotoxicity. http://togogenome.org/gene/10090:Tmem126a ^@ http://purl.uniprot.org/uniprot/Q9D8Y1 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM126 family.|||In the retina, significant levels of expression are detected in the ganglion cell layer, the optic nerve head, the outer plexiform layer, and in the outer ellipsoide length of photoreceptor inner segments.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Jdp2 ^@ http://purl.uniprot.org/uniprot/P97875 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. ATF subfamily.|||Component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Involved in a variety of transcriptional responses associated with AP-1, such as UV-induced apoptosis, cell differentiation, tumorigenesis and antitumogeneris. Can also function as a repressor by recruiting histone deacetylase 3/HDAC3 to the promoter region of JUN. May control transcription via direct regulation of the modification of histones and the assembly of chromatin (By similarity).|||Forms a homodimer or heterodimer with JUN, JUNB, JUND, CEBPG and ATF2 thereby inhibiting transactivation by JUN, ATF2 and CEBPG (By similarity). Binds multiple DNA elements such as cAMP-response element (CRE) and TPA response element (TRE) either as homodimer or heterodimer. Interacts with IRF2BP1 (By similarity).|||Nucleus|||Phosphorylation of Thr-148 by MAPK8 in response to different stress conditions such as, UV irradiation, oxidatives stress and anisomycin treatments.|||Polyubiquitinated; probably by IRF2BP1.|||Ubiquitously expressed in all adult tissues tested as well in embryos. http://togogenome.org/gene/10090:Hrh2 ^@ http://purl.uniprot.org/uniprot/P97292 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||The H2 subclass of histamine receptors mediates gastric acid secretion. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. http://togogenome.org/gene/10090:Rac2 ^@ http://purl.uniprot.org/uniprot/Q05144 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cytoplasm|||Interacts with DOCK2, which may activate it. Interacts with S100A8 and calprotectin (S100A8/9) (By similarity). Found in a complex with SH3RF1, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103). Interacts with PAK1 (By similarity).|||Membrane|||Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as secretory processes, phagocytose of apoptotic cells and epithelial cell polarization. Augments the production of reactive oxygen species (ROS) by NADPH oxidase.|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. http://togogenome.org/gene/10090:Myf6 ^@ http://purl.uniprot.org/uniprot/P15375|||http://purl.uniprot.org/uniprot/Q0VEJ7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Interacts with CSRP3.|||Involved in muscle differentiation (myogenic factor). Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.|||Nucleus|||Skeletal muscle. http://togogenome.org/gene/10090:B4galnt2 ^@ http://purl.uniprot.org/uniprot/A2A615|||http://purl.uniprot.org/uniprot/Q09199 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family.|||Golgi apparatus membrane|||Membrane|||Responsible for synthesis of murine T-lymphocyte CT antigen. Can transfer N-acetylgalactosamine moiety from UDP-GalNAc to the low molecular weight acceptor 3'-sialyl-N-acetyllactosamine, to form a non-reducing terminal tetrasaccharide Sda blood group structure. http://togogenome.org/gene/10090:Ndrg2 ^@ http://purl.uniprot.org/uniprot/Q9QYG0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NDRG family.|||Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes, such as CCND1, and may thereby act as tumor suppressor. May be involved in dendritic cell and neuron differentiation (By similarity).|||Cytoplasm|||Expressed at highest levels in brain, heart and liver, and at lower levels in kidney, colon, skeletal muscle, adrenal gland, ovary and uterus (at protein level).|||Expression is restricted to the developing heart at the stage of 9.5 dpc, and increases after 11.5 dpc as development of tissues and organs proceeds. Present in many developing tissues including heart, brain, lung, liver, gut, kidney, skeletal muscle, cartilage and epidermis (at protein level).|||Interacts with CTNNB1.|||growth cone|||perinuclear region http://togogenome.org/gene/10090:Nxpe5 ^@ http://purl.uniprot.org/uniprot/E0CX47|||http://purl.uniprot.org/uniprot/E9PXC9 ^@ Similarity ^@ Belongs to the NXPE family. http://togogenome.org/gene/10090:Papss2 ^@ http://purl.uniprot.org/uniprot/A0A494B923|||http://purl.uniprot.org/uniprot/O88428 ^@ Disease Annotation|||Function|||Similarity|||Tissue Specificity ^@ Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate/PAPS, the activated sulfate donor used by sulfotransferases (PubMed:10559207). In mammals, PAPS is the sole source of sulfate while APS appears to only be an intermediate in the sulfate-activation pathway. May have an important role in skeletogenesis during postnatal growth.|||Defects in Papss2 are the cause of brachymorphism (bm), a autosomal recessive disease, which is characterized by abnormal hepatic detoxification, bleeding times and postnatal growth, such as dome-shaped skull, short thick tail, and shortened but not widened limbs. The abnormal postnatal growth has been attributed to undersulfation of cartilage proteoglycans.|||Expressed in liver, cartilage, skin and brain.|||In the C-terminal section; belongs to the sulfate adenylyltransferase family.|||In the N-terminal section; belongs to the APS kinase family. http://togogenome.org/gene/10090:Scp2 ^@ http://purl.uniprot.org/uniprot/P32020 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains a putative mitochondrial transit peptide at positions 1-20.|||Cytoplasm|||Endoplasmic reticulum|||In testis, expressed in the interstitial connective tissue, an area rich in interstitial cells of Leydig at lower levels than isoform SCPx.|||In testis, highly expressed in the interstitial connective tissue, an area rich in interstitial cells of Leydig, but it is barely expressed in the germ cells of the seminiferous tubule.|||In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family.|||Interacts with PEX5; the interaction is essential for peroxisomal import.|||Knockouts are viable and fertile (PubMed:9553048). Mutants show alterations in hepatic gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control and neuropathy (PubMed:9553048).|||Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis (By similarity). Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol (By similarity). Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA (PubMed:9553048). Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides (PubMed:11003606). Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3 (PubMed:11003606). Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (PubMed:9553048).|||Mitochondrion|||Peroxisome|||Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids (PubMed:10706581). Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA) (PubMed:10706581). Also active with medium and long straight chain 3-oxoacyl-CoAs (By similarity). Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro (By similarity). Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (PubMed:9553048).|||Present at low levels in all tissues examined but expressed predominantly in the liver.|||preSCP2, a protein with a molecular mass of about 15 kDa, is processed into its mature form (SCP2) by proteolytic cleavage of a 20 residue leader sequence after translocation into peroxisomes. http://togogenome.org/gene/10090:Pgpep1l ^@ http://purl.uniprot.org/uniprot/E9QM76|||http://purl.uniprot.org/uniprot/Q9CWB5 ^@ Similarity ^@ Belongs to the peptidase C15 family. http://togogenome.org/gene/10090:Mospd2 ^@ http://purl.uniprot.org/uniprot/Q9CWP6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and endosomes, mitochondria or Golgi through interaction with conventionnal- and phosphorylated-FFAT-containing organelle-bound proteins. In addition, forms endoplasmic reticulum (ER)-lipid droplets (LDs) contacts through a direct protein-membrane interaction and participates in LDs homeostasis. The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs. Promotes migration of primary monocytes and neutrophils, in response to various chemokines.|||Homooligomer. Interacts (via MSP domain) with STARD3NL (via FFAT motif), RMDN3 (via FFAT motif), OSBPL1A (via FFAT motif) and CERT1 (via FFAT motif). Interacts (via MSP domain) with STARD3 (via phosphorylated FFAT motif); this interaction depends on the critical phosphorylation of STARD3 on 'Ser-209'. Interacts with RB1CC1 (via phosphorylated FFAT motif), MIGA2 (via phosphorylated FFAT motif) and OSBPL1A (via FFAT motif).|||The CRAL-TRIO domain is necessary for the recruitment to lipid droplets (LDs) and mediates the formation of ER-LDs contacts through an amphipathic helix.|||The MSP domain is required for binding to the FFAT motif of target proteins.|||The transmembrane domain is necessary for binding to LDs. http://togogenome.org/gene/10090:Gm13043 ^@ http://purl.uniprot.org/uniprot/Q4FZF9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Dnajc24 ^@ http://purl.uniprot.org/uniprot/Q91ZF0 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A nucleotide mismatch versus the mouse genome results in the formation of an upstream ATG start codon.|||Belongs to the DPH4 family.|||Detected in heart, brain, spleen, lung, liver, kidney and testis.|||High embryonic lethality at 14.5 dpc. As early as 10.5 dpc, embryos are smaller than their wild-type littermates. Embryos that survive long enough to initiate digit formation show one or more additional preaxial digits.|||Monomer and homooligomer. Iron binding promotes oligomerization (By similarity).|||The DPH-type metal-binding (MB) domain can bind either zinc or iron ions.|||The iron-bound form is redox-active and can function as electron carrier (By similarity). Stimulates the ATPase activity of several Hsp70-type chaperones. This ability is enhanced by iron-binding. Plays a role in the diphthamide biosynthesis, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2).|||cytoskeleton http://togogenome.org/gene/10090:Ctsb ^@ http://purl.uniprot.org/uniprot/P10605 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the peptidase C1 family.|||Dimer of a heavy chain and a light chain cross-linked by a disulfide bond. Interacts with SRPX2. Directly interacts with SHKBP1.|||Enlarged thyroid follicles, reduced extension of the thyroid epithelium, and increased levels of Tg/thyroglobulin in the thyroid follicles which fails to assemble into multilayers. Lysosomes are enlarged and CTSK/cathepsin K is absent from the thyroid follicle lumen and mis-localizes to the apical membrane of thyroid epithelial cells.|||Expressed in thyroid epithelial cells.|||Lysosome|||Melanosome|||Thiol protease which is believed to participate in intracellular degradation and turnover of proteins (By similarity). Cleaves matrix extracellular phosphoglycoprotein MEPE (By similarity). Involved in the solubilization of cross-linked TG/thyroglobulin in the thyroid follicle lumen (PubMed:12782676). Has also been implicated in tumor invasion and metastasis (By similarity).|||extracellular space http://togogenome.org/gene/10090:Reg2 ^@ http://purl.uniprot.org/uniprot/Q08731 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed only in regenerating islets and normal exocrine pancreas, but not in normal pancreatic islets. Expressed strongly in pancreas, weakly in liver, but not at all in gall bladder.|||Might act as an inhibitor of spontaneous calcium carbonate precipitation.|||Secreted http://togogenome.org/gene/10090:Serpina1d ^@ http://purl.uniprot.org/uniprot/Q00897 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Inhibitor of serine proteases. Can inhibit trypsin and chymotrypsin; relatively ineffective against elastase.|||Murine alpha-1-antitrypsin is represented by a cluster of up to 6 individual Serpina1-related genes. The precise complement of Serpina1-related genes present varies according to the strain of the animal.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity. http://togogenome.org/gene/10090:Tube1 ^@ http://purl.uniprot.org/uniprot/Q9D6T1 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Found in a complex with TEDC1, TEDC2, TUBE1 and TUBD1.|||centrosome http://togogenome.org/gene/10090:Or52z1 ^@ http://purl.uniprot.org/uniprot/F8VPJ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adm2 ^@ http://purl.uniprot.org/uniprot/Q7TNK8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the adrenomedullin family.|||High expression detected in the submaxillary gland, kidney, stomach, and mesentery, followed by the pituitary, lung, pancreas, intestines, spleen, thymus and ovary. Expressed mainly in the intermediate lobe of the pituitary, with sporadic in the anterior lobe.|||May play a role as physiological regulators of gastrointestinal, cardiovascular bioactivities mediated by the CALCRL/RAMPs receptor complexes. Activates the cAMP-dependent pathway.|||Secreted http://togogenome.org/gene/10090:Slc35d3 ^@ http://purl.uniprot.org/uniprot/Q8BGF8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alternatively, could function as a molecular adapter enhancing the formation of the PI3KC3-C1/AIC/autophagy initiation complex to promote autophagy in dopaminergic neurons (PubMed:27171858). Could also regulate the plasma membrane localization of the D(1A) dopamine receptor/DRD1 and dopamine signaling (PubMed:24550737).|||Belongs to the TPT transporter family. SLC35D subfamily.|||Could interact with ATG14, BECN1 and PIK3C3 that form the PI3KC3-C1/AIC/autophagy initiation complex; enhancing the formation of the AIC and promoting autophagy.|||Early endosome membrane|||Endoplasmic reticulum membrane|||Expressed in brain (PubMed:17062724). Expressed in subsets of dopaminergic neurons (PubMed:27171858). Expressed in maturing megakaryocytes (PubMed:22611153).|||Inhibited by proton uncouplers that directly abolish the proton electrochemical gradient.|||Mice lacking Slc35d3 display decreased concentrations of serotonin in platelet-dense granules and altered hemostasis (PubMed:17062724, PubMed:22611153). Mice also show a loss of dopaminergic neurons and exhibit metabolic syndrome and lowered energy expenditure (PubMed:24550737, PubMed:27171858).|||Probable UDP-glucose transmembrane transporter involved in UDP-glucose transport from the cytosol to the lumen of synaptic vesicles (PubMed:34269178). It is involved in platelet dense granules maturation (PubMed:17062724, PubMed:22611153).|||synaptic vesicle membrane http://togogenome.org/gene/10090:Or2o1 ^@ http://purl.uniprot.org/uniprot/Q8VET2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5p73 ^@ http://purl.uniprot.org/uniprot/Q8VEW2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Serp2 ^@ http://purl.uniprot.org/uniprot/Q6TAW2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RAMP4 family.|||Endoplasmic reticulum membrane|||May interact with target proteins during translocation into the lumen of the endoplasmic reticulum. May protect unfolded target proteins against degradation and facilitate correct glycosylation (Potential).|||Membrane http://togogenome.org/gene/10090:Mterf1a ^@ http://purl.uniprot.org/uniprot/Q8CHZ9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mTERF family.|||Contains nine structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a left-handed superhelical assembly with a solenoid structure that wraps itself around DNA (By similarity).|||Double knockout of Mterf1a and Mterf1b results in viable animals with no gross phenotype, and normal oxidative phosphorylation capacity. Steady-state mitochondrial DNA levels are normal. There are subtle effects on levels of mitochondrial transcripts: transcripts initiated at the light strand promoter and also downstream of the MTERF binding site are increased, levels of 7S RNA are reduced, while levels of other mitochondrial transcripts are normal.|||Mitochondrion|||Monomer.|||Phosphoprotein with mostly four phosphate groups. While the DNA-binding activity is unaffected by the phosphorylation state, only the phosphorylated form of the protein is active for termination activity. Functioning seems to be regulated by phosphorylation (By similarity).|||Predominantly expressed in heart and liver, with extremely low levels in other tissues (PubMed:15582606). Expressed strongly in the heart and at lower levels in brain, liver and kidney (PubMed:23562081).|||Transcription termination factor. Binds to a 28 bp region within the tRNA(Leu(uur)) gene at a position immediately adjacent to and downstream of the 16S rRNA gene; this region comprises a tridecamer sequence critical for directing accurate termination. Binds DNA along the major grove and promotes DNA bending and partial unwinding. Promotes base flipping. Transcription termination activity appears to be polarized with highest specificity for transcripts initiated on the light strand. http://togogenome.org/gene/10090:Srsf12 ^@ http://purl.uniprot.org/uniprot/Q8C8K3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the splicing factor SR family.|||In contrast to the human ortholog, lacks the RRM (RNA recognition motif) domain at the N-terminus.|||Nucleus|||Splicing factor that seems to antagonize SR proteins in pre-mRNA splicing regulation. http://togogenome.org/gene/10090:Abcg4 ^@ http://purl.uniprot.org/uniprot/Q91WA9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family that may be involved in the cellular efflux of sterols, in particular cholesterol and desmosterol (a cholesterol precursor), to high-density lipoprotein (HDL) (PubMed:15210959, PubMed:18039927, PubMed:17916878). May play an important role in the removal of amyloid-beta peptides from brain, in a process that can be antagonized by desmosterol. However it is unclear whether ABCG4 can directly transport amyloid-beta peptides or whether peptide export may be facilitated due to changes in the membrane lipid environment (PubMed:29042617). Induces apoptosis in various cells (By similarity).|||Abcg4 deficiency does not significantly affect the levels of sterols in the brain except for brain lathosterol levels, which are slightly elevated (PubMed:18039927). Abcg1/Abcg4 double knockout mice display significant accumulation of 24(S)-hydroxycholesterol (24S-HC) and 27-hydroxy-cholesterol (27-HC) in addition to the cholesterol synthesis intermediates, desmosterol, lanosterol and lathosterol (PubMed:19633360, PubMed:18039927).|||Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Endosome membrane|||Half-transporter that forms a functional transporter via homo- or heterodimerization. Homodimer. Heterodimers with ABCG1.|||Highly but transiently expressed in enterocytes and hemopoietic cells populating the liver during development, but is absent when animals are fully developed. Highly expressed in the eyes of the developing embryos as early as 12.5 dpc and developing CNS.|||Highly expressed in the brain, in particular in neurons, microglia and astrocytes (PubMed:11856881, PubMed:12183068, PubMed:18039927, PubMed:17916878). Expressed on blood brain barrier endothelial cells (PubMed:29042617). Expressed in the spleen (PubMed:11856881).|||Whether ABCG4 is an LXR target gene, is still under debate. Studies performed in monocytes, and in one astrocyte cell line indicated that ABCG4 expression could be up-regulated by oxysterols and other LXR ligands (By similarity). However, subsequent observations in a number of different cell types (primary mouse cells, oligodendrocytes and neuron-like cell lines) have not confirmed this observation (PubMed:17916878) (By similarity). http://togogenome.org/gene/10090:Rps6ka3 ^@ http://purl.uniprot.org/uniprot/B1AXN9|||http://purl.uniprot.org/uniprot/P18654 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation at Ser-227 by PDPK1. Autophosphorylated on Ser-386, as part of the activation process. May be phosphorylated at Thr-365 and Ser-369 by MAPK1/ERK2 and MAPK3/ERK1. Can also be activated via phosphorylation at Ser-386 by MAPKAPK2.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Cytoplasm|||Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation (By similarity). Interacts with NFATC4, ETV1/ER81 and FGFR1 (By similarity).|||Intestine, thymus, lung, heart and brain.|||Mice were born at expected Mendelian ratio but display decreased bone mass (PubMed:15109498). Embryos and pups show a delay in mineralization of the skull with frontal, parietal, and interparietal bones of reduced size (PubMed:15109498). Mice also display a significant reduction in long bone length at one month of age (PubMed:15109498).|||N-terminal myristoylation results in an activated kinase in the absence of added growth factors.|||Nucleus|||Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10856237, PubMed:15109498). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (By similarity). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (By similarity). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (By similarity). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (By similarity). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (By similarity). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (By similarity). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (By similarity). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (By similarity). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:14504289). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (PubMed:17785202, PubMed:17906627). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (PubMed:22827337). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (PubMed:22827337). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (By similarity). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (PubMed:15109498).|||Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-577 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser-227 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD (By similarity). http://togogenome.org/gene/10090:Mag ^@ http://purl.uniprot.org/uniprot/P20917 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adhesion molecule that mediates interactions between myelinating cells and neurons by binding to neuronal sialic acid-containing gangliosides and to the glycoproteins RTN4R and RTN4RL2 (PubMed:7533044, PubMed:12089450, PubMed:27922006). Not required for initial myelination, but seems to play a role in the maintenance of normal axon myelination (PubMed:7516497, PubMed:9262180, PubMed:9482781, PubMed:9482783, PubMed:9469574, PubMed:10625334). Protects motoneurons against apoptosis, also after injury; protection against apoptosis is probably mediated via interaction with neuronal RTN4R and RTN4RL2 (PubMed:26335717). Required to prevent degeneration of myelinated axons in adults; this probably depends on binding to gangliosides on the axon cell membrane (PubMed:15953602, PubMed:19158290). Negative regulator of neurite outgrowth that inhibits axon longitudinal growth (PubMed:19158290, PubMed:27922006, PubMed:12089450). Negative regulator of neurite outgrowth; in dorsal root ganglion neurons the inhibition is mediated primarily via binding to neuronal RTN4R or RTN4RL2 and to a lesser degree via binding to neuronal gangliosides (PubMed:17640868). In cerebellar granule cells the inhibition is mediated via binding to neuronal gangliosides (PubMed:17640868). In sensory neurons, inhibition of neurite extension depends only partially on RTN4R, RTN4RL2 and gangliosides (By similarity). Inhibits axon outgrowth by binding to RTN4R (PubMed:12089450). Preferentially binds to alpha-2,3-linked sialic acid (PubMed:7533044, PubMed:27922006). Binds ganglioside Gt1b (PubMed:27922006).|||Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||Cell membrane|||Detected in the myelin tract in brain, especially in the corpus callosum and in peripheral nerve (PubMed:7516497, PubMed:9482783, PubMed:24191038). Expressed by myelinating glial cells in the central and peripheral nervous system (PubMed:10625334). Detected in oligodendrocyte processes before formation of compact myelin (PubMed:2474006, PubMed:10625334). Restricted to the periaxonal space after myelination (PubMed:10625334). Isoform S-MAG is the predominant isoform in CNS and PNS of the adult (at protein level) (PubMed:1716323).|||In CNS isoform L-MAG is the major form synthesized early in development, and it persists as a significant proportion of the MAG present in the adult. In the PNS isoform L-MAG is expressed at modest levels during development; it is absent in the adult.|||Membrane raft|||Monomer and homodimer (PubMed:27922006). Interacts (via the first three N-terminal Ig-like domains) with RTN4R and RTN4RL2 (PubMed:12089450, PubMed:26335717). Interacts with isoform 2 of BSG (PubMed:12558975).|||Mutant mice appear normal, excepting subtle defects in motor coordination and a slight intention tremor (PubMed:7516497). They have similar numbers of motoneurons as wild-type at birth, but display an important loss of motoneurons during the first week after birth (PubMed:26335717).Five month old mutant mice display a decreased ability to remain on a rotating cylinder (PubMed:15953602). Contrary to wild-type, about 40% of mutant mice have severe episodes of whole-body tremor, both during movement and when resting (PubMed:15953602). The myelination in brain and around peripheral nerves appears grossly normal in young animals, but the periaxonal cytoplasmic collar is often missing in optic nerve (PubMed:7516497, PubMed:9262180, PubMed:9482781, PubMed:9469574). When present, the cytoplasm of the periaxonal collar has generally a disorganized aspect (PubMed:7516497). Mutant mice have an increased percentage of unmyelinated axons in optic nerve (PubMed:9262180, PubMed:9469574). Besides, a small proportion of nerves from mutant mice display redundant myelination, and also rare cases of multiple myelination, where axons are surrounded by two or more compact myelin sheets (PubMed:9469574). Sciatic nerves from over three month old mutant mice show signs of Wallerian degeneration, with redundant myelin, degeneration of myelinated fibers, and an apparent decrease in the diameter of myelinated axons (PubMed:9482781, PubMed:15953602). The distances between neurofilaments in myelinated axons from over 3 month old mice are shorter than normal (PubMed:9482781, PubMed:15953602). With increasing age, mutant mice display progressive axon degeneration in the spinal cord and sciatic nerve, resulting in a decrease of 28% in the number of spinal cord axons after 15 months (PubMed:19158290). Mutant mice display increased motoneuron apoptosis after injury (PubMed:26335717). Likewise, they display strongly increased axon degeneration after treatment with the neurotoxin acrylamide (PubMed:19158290). Mutant mice display much more severe axon loss in response to experimental autoimmune encephalitis (PubMed:19158290).|||N-glycosylated.|||Phosphorylated on tyrosine residues.|||The C-terminal cytoplasmic region found only in isoform L-MAG is required for normal myelination in the central nervous system (CNS), but is apparently not required for normal myelination in the peripheral nervous system (PNS).|||The extracellular domain is required to protect against axon degeneration (PubMed:19158290, PubMed:26335717). The first three Ig-like domains mediate interaction with RTN4R and RTN4RL2, but are not sufficient to inhibit neurite outgrowth (By similarity). The two C-terminal extracellular Ig-like C2-type domains are required for inhibition of axon longitudinal growth. Besides, the two C-terminal extracellular Ig-like C2-type domains are required for protection against apoptosis after nerve injury (PubMed:26335717).|||Ubiquitinated, leading to proteasomal degradation. http://togogenome.org/gene/10090:Smim22 ^@ http://purl.uniprot.org/uniprot/J3QP37|||http://purl.uniprot.org/uniprot/V9GXA9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Mptx2 ^@ http://purl.uniprot.org/uniprot/D3YYJ7 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pentraxin family.|||Binds 2 calcium ions per subunit.|||Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.|||Secreted http://togogenome.org/gene/10090:Col14a1 ^@ http://purl.uniprot.org/uniprot/Q80X19 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.|||Homotrimer.|||Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in all cases and bind carbohydrates.|||May contain numerous cysteine residues involved in inter- and intramolecular disulfide bonding.|||Plays an adhesive role by integrating collagen bundles. It is probably associated with the surface of interstitial collagen fibrils via COL1. The COL2 domain may then serve as a rigid arm which sticks out from the fibril and protrudes the large N-terminal globular domain into the extracellular space, where it might interact with other matrix molecules or cell surface receptors (By similarity).|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||extracellular matrix http://togogenome.org/gene/10090:Chm ^@ http://purl.uniprot.org/uniprot/A2AD03|||http://purl.uniprot.org/uniprot/Q3UR39|||http://purl.uniprot.org/uniprot/Q8CBI2|||http://purl.uniprot.org/uniprot/Q9CS14 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Rab GDI family.|||Cytoplasm|||Substrate-binding subunit (component A) of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane. http://togogenome.org/gene/10090:Opn4 ^@ http://purl.uniprot.org/uniprot/Q9QXZ9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ About 40 times more abundant than isoform 1 in the retina (at protein level) (PubMed:19793992). Isoform 2 is involved in processes localized to the outer IPL or is bistratified with processes in both the inner and outer layers of the IPL (at protein level) (PubMed:19793992). Isoform 2 is absent in the processes confined only to the inner layer of the IPL (at protein level) (PubMed:19793992).|||Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Cell membrane|||Expressed in the inner retina at postnatal day 5 (P5), and expressed in retinal ganglion cells at P12.|||Expressed in the retinal pigment epithelium and ganglion cell layer (at protein level) (PubMed:10632589, PubMed:30240620, PubMed:31607531). Also expressed in amacrine cell layers of the retina (PubMed:10632589). Weakly expressed in vibrissae, and tail (PubMed:31607531).|||Mice fail to show a pupillar reflex, photoentrainment of the circadian clock and other non-image forming responses to light (PubMed:12808468). Newborn mice show normal hyaloid vessel numbers and normal vessel cellularity, however vessel numbers are increased by P8 (PubMed:30936473). In Opn4 and Pde6b double knockout mice optokinetic visual tracking response is abolished (PubMed:26392540).|||Observed with processes in the outer strata of inner plexiform layer (IPL) close to the inner nuclear layer (INL) or is found to be bistratified with processes located both in the inner (ON) or outer (OFF) layers of the IPL (at protein level) (PubMed:19793992). A second population of isoform 1 is identified in processes which are confined to the inner layer of the IPL near to the ganglion cell layer (GCL) (at protein level) (PubMed:19793992).|||Perikaryon|||Photoreceptor that binds cis-retinaldehydes (PubMed:19793992). Contributes to pupillar reflex, photoentrainment and other non-image forming responses to light (PubMed:12808468). May be involved in the optokinetic visual tracking response (PubMed:26392540). May be involved in the regulation of retinal hyaloid vessel growth and regression (PubMed:30936473).|||axon|||dendrite http://togogenome.org/gene/10090:Fbll1 ^@ http://purl.uniprot.org/uniprot/Q80WS3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methyltransferase superfamily. Fibrillarin family.|||By homology to other fibrillarins, some or all of the N-terminal domain arginines are modified to asymmetric dimethylarginine (DMA).|||S-adenosyl-L-methionine-dependent methyltransferase that has the ability to methylate both RNAs and proteins. Involved in pre-rRNA processing by catalyzing the site-specific 2'-hydroxyl methylation of ribose moieties in pre-ribosomal RNA. Also acts as a protein methyltransferase by mediating methylation of glutamine residues (By similarity).|||nucleolus http://togogenome.org/gene/10090:Slc25a16 ^@ http://purl.uniprot.org/uniprot/Q8C0K5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||May be involved in the transport of coenzyme A in the mitochondrial matrix. Very little is known about the physiological function of this carrier.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cnksr2 ^@ http://purl.uniprot.org/uniprot/Q80YA9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNKSR family.|||Cytoplasm|||Interacts with RAF1, RAB2L and RAL GTPase proteins.|||May function as an adapter protein or regulator of Ras signaling pathways.|||Membrane|||Phosphorylated on tyrosine. http://togogenome.org/gene/10090:Dusp13a ^@ http://purl.uniprot.org/uniprot/Q6B8I0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Expressed at very low levels in myotubes and early postnatal muscle. Expression markedly increases at approximately the 3rd week after birth and continues to increase gradually into adulthood.|||Monomer. Interacts with MAP3K5/ASK1; may compete with AKT1 preventing MAP3K5/ASK1 phosphorylation by AKT1.|||Probable protein tyrosine phosphatase. Has phosphatase activity with synthetic substrates. Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.|||Skeletal muscle-specific. http://togogenome.org/gene/10090:Serpina5 ^@ http://purl.uniprot.org/uniprot/P70458|||http://purl.uniprot.org/uniprot/Q8BVN1 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:11120760 it is not detectable in blood plasma.|||Belongs to the serpin family.|||Forms protease inhibiting heterodimers in extracellular body fluids with serine proteases such as activated protein C/coagulation factor V/F5, acrosin/ACR, chymotrypsinogen B/CTRB1, prothrombin/F2, factor Xa/F10, factor XI/F11, kallikrein/KLKB1, tissue kallikrein, trypsin/PRSS1, prostate specific antigen/KLK3, tissue plasminogen activator/PLAT and urinary plasminogen activator/PLAU. Forms membrane-anchored serine proteases inhibiting heterodimers with TMPRSS7 and TMPRSS11E. Interacts with SEMG2 (By similarity).|||Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and pro-inflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue- and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid (By similarity).|||Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans, heparin, thrombomodulin and phospholipids vesicles.|||Mice are healthy but males are infertile; spermatozoa are morphologically abnormal, most lacked tails and malformed heads. The lumina of the seminiferous tubules are filled with cells in different stages of spermatogenesis and are sometimes necrotic. The cytoplasm of Sertoli cells contained vacuoles and appeared necrotic. The Sertoli cell barrier appeared disrupted.|||N-glycosylated; glycans consist of a mixture of sialylated bi- (including sialyl-Lewis X epitopes), tri- and tetra-antennary complex-type chains; affects the maximal heparin- and thrombomodulin-enhanced rates of thrombin inhibition. O-glycosylated; further modified with 2 sialic acid residues. Proteolytically cleaved at the N-terminus; inhibits slightly the heparin- and thrombomodulin-enhanced rates of thrombin inhibition (By similarity).|||Not detected in blood plasma (at protein level). Expressed in testis, epididymis, seminal vesicles, prostate and ovaries.|||Proteolytically cleaved. Inhibition of proteases is accompanied by formation of a stable enzyme-inhibitor complex and by degradation of the serpin to lower molecular weight derivatives (By similarity).|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity).|||extracellular space http://togogenome.org/gene/10090:Edrf1 ^@ http://purl.uniprot.org/uniprot/Q6GQV7 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Transcription factor involved in erythroid differentiation. Involved in transcriptional activation of the globin gene (By similarity). http://togogenome.org/gene/10090:Trmt112 ^@ http://purl.uniprot.org/uniprot/Q5M8M3|||http://purl.uniprot.org/uniprot/Q9DCG9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the testis, also expressed in the brain, heart, kidney, liver, lung, muscle and spleen.|||Acts as an activator of both rRNA/tRNA and protein methyltransferases (PubMed:20606008, PubMed:26797129). Together with methyltransferase BUD23, methylates the N(7) position of a guanine in 18S rRNA (By similarity). The heterodimer with HEMK2/N6AMT1 catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:20606008, PubMed:26797129). The heterodimer with ALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA species (By similarity). Together with methyltransferase THUMPD3, catalyzes the formation of N(2)-methylguanosine at position 6 in a broad range of tRNA substrates and at position 7 of tRNA(Trp) (By similarity). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production (By similarity). Together with methyltransferase METTL5, specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (By similarity).|||Belongs to the TRM112 family.|||Heterodimer with BUD23/WBSCR22; this heterodimerization is necessary for the metabolic stability and activity of the catalytic subunit BUD23 (By similarity). Heterodimer with N6AMT1/HEMK2; this heterodimerization is necessary for S-adenosyl-L-methionine-binding to N6AMT1/HEMK2 (PubMed:26797129). Heterodimer with ALKBH8 (By similarity). Heterodimer with METTL5; this heterodimerization is necessary for the stability of the catalytic subunit METTL5 (By similarity). Interacts with THUMPD3; the interaction is direct and is required for THUMPD3 methyltransferase activity (By similarity). Interacts with THUMPD2 (By similarity).|||nucleoplasm|||perinuclear region http://togogenome.org/gene/10090:Ndufb9 ^@ http://purl.uniprot.org/uniprot/Q9CQJ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I LYR family.|||Mammalian complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gid8 ^@ http://purl.uniprot.org/uniprot/Q9D7M1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GID8 family.|||Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. Acts as a positive regulator of Wnt signaling pathway by promoting beta-catenin (CTNNB1) nuclear accumulation.|||Cytoplasm|||Homodimer; may also form higher oligomers (PubMed:27920276). Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with RANBP9. Part of a complex consisting of RANBP9, MKLN1 and GID8. Interacts with CTNNB1, AXIN1 and GSK3B (By similarity).|||Nucleus|||Polyubiquitinated through 'Lys-48'-polyubiquitin chains, leading to proteasomal degradation in the absence of Wnt stimulation.|||Ubiquitous. http://togogenome.org/gene/10090:Zfp319 ^@ http://purl.uniprot.org/uniprot/Q9ERR8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Pla2g12a ^@ http://purl.uniprot.org/uniprot/Q9EPR2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Cytoplasm|||PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Does not exhibit detectable activity toward sn-2-arachidonoyl- or linoleoyl-phosphatidylcholine or -phosphatidylethanolamine (By similarity).|||Secreted http://togogenome.org/gene/10090:Zfp41 ^@ http://purl.uniprot.org/uniprot/Q02526 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A putative DNA-binding regulatory protein associated with meiosis in spermatogenesis.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Detected in the newborn testis and peaks at 3 weeks during the first cycle of spermatogenesis. Expressed in the fetus and embryo.|||Nucleus|||Predominantly in the spermatocytes and spermatids of testes. It is also expressed in the fetus and embryonic stem cells at lower levels. http://togogenome.org/gene/10090:Gm20738 ^@ http://purl.uniprot.org/uniprot/Q810R8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Fgf4 ^@ http://purl.uniprot.org/uniprot/A0A7U3JW80|||http://purl.uniprot.org/uniprot/P11403 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Expressed in the blastocyst inner cell mass and later in distinct embryonic tissues.|||Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation. Is essential for survival of the postimplantation mouse embryo. Required for normal limb and cardiac valve development during embryogenesis. May play a role in embryonic molar tooth bud development via inducing the expression of MSX1, MSX2 and MSX1-mediated expression of SDC1 in dental mesenchyme cells (PubMed:8898217).|||Secreted http://togogenome.org/gene/10090:Pcdhga6 ^@ http://purl.uniprot.org/uniprot/Q91XY2 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Nsmce4a ^@ http://purl.uniprot.org/uniprot/G3XA30 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NSE4 family.|||Component of the SMC5-SMC6 complex, that promotes sister chromatid alignment after DNA damage and facilitates double-stranded DNA breaks (DSBs) repair via homologous recombination between sister chromatids.|||Component of the SMC5-SMC6 complex.|||Nucleus|||telomere http://togogenome.org/gene/10090:Usp30 ^@ http://purl.uniprot.org/uniprot/Q3UN04 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C19 family.|||Deubiquitinating enzyme tethered to the mitochondrial outer membrane that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes ubiquitin attached by parkin on target proteins, such as RHOT1/MIRO1 and TOMM20, thereby blocking parkin's ability to drive mitophagy. Preferentially cleaves 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, 2 types of linkage that participate in mitophagic signaling. Does not cleave efficiently polyubiquitin phosphorylated at 'Ser-65' (By similarity). Acts as negative regulator of mitochondrial fusion by mediating deubiquitination of MFN1 and MFN2 (PubMed:24513856).|||Inhibited by the diterpenoid derivative 15-oxospiramilactone (S3).|||Mitochondrion outer membrane|||Ubiquitinated by parkin (PRKN) at Lys-235 and Lys-289, leading to its degradation. http://togogenome.org/gene/10090:Nomo1 ^@ http://purl.uniprot.org/uniprot/Q6GQT9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the back of Sec61 (BOS) complex, composed of NCLN/Nicalin, NOMO (NOMO1, NOMO2 or NOMO3) and TMEM147. The BOS complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.|||Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Slc6a5 ^@ http://purl.uniprot.org/uniprot/B2RQX9|||http://purl.uniprot.org/uniprot/B2RXV9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Membrane http://togogenome.org/gene/10090:Ndufb11 ^@ http://purl.uniprot.org/uniprot/O09111 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB11 subunit family.|||Complex I is composed of 45 different subunits. Interacts with BCAP31.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Zxdc ^@ http://purl.uniprot.org/uniprot/Q8C8V1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZXD family.|||Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.|||Nucleus|||Self-associates. Interacts with ZXDB and CIITA (By similarity).|||Sumoylated at Lys-661 with SUMO1, SUMO2 and SUMO3; sumoylation enhances the activity of the transcriptional activation domain. http://togogenome.org/gene/10090:Fgfr1op2 ^@ http://purl.uniprot.org/uniprot/Q9CRA9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SIKE family.|||Cytoplasm|||May be involved in wound healing pathway. http://togogenome.org/gene/10090:Ankrd49 ^@ http://purl.uniprot.org/uniprot/Q8VE42 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in liver at embryonic stage 13 dpc, and in liver, brain and lung at 16 dpc (PubMed:11162141). In testis, expression levels steadily increase from 1 week after birth and plateau by 8 weeks after birth (PubMed:26043108).|||Expressed in spermatogonia, spermatocytes and round spermatids.|||May have a role in spermatogenesis where it promotes autophagy in response to serum starvation, via the NF-kappaB pathway.|||Nucleus http://togogenome.org/gene/10090:Gm20892 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Tgfbr2 ^@ http://purl.uniprot.org/uniprot/Q3UG22|||http://purl.uniprot.org/uniprot/Q543C0|||http://purl.uniprot.org/uniprot/Q62312|||http://purl.uniprot.org/uniprot/Q8BQS9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Has transforming growth factor beta-activated receptor activity.|||Homodimer. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGFRB1 and TGFRB2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1 (By similarity). Interacts with DAXX. Interacts with DYNLT4. Interacts with ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor (By similarity). Interacts with and is activated by SCUBE3; this interaction does not affect TGFB1-binding to TGFBR2 (By similarity). Interacts with VPS39; this interaction is independent of the receptor kinase activity and of the presence of TGF-beta (By similarity). Interacts with CLU (By similarity).|||Membrane|||Membrane raft|||Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.|||Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways (By similarity).|||Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways.|||Widely expressed in adult. Expressed primarily in mesenchyme and epidermis of the midgestational fetus. http://togogenome.org/gene/10090:Nudt16l1 ^@ http://purl.uniprot.org/uniprot/Q8VHN8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although strongly related to the nudix NUDT16 protein, lacks the Nudix box and is therefore not related to the rest of the family. Lacks a number of residues which are necessary for hydrolase activity and does not play a role in U8 snoRNA decapping activity.|||Belongs to the Nudix hydrolase family. TIRR subfamily.|||Homodimer (PubMed:26100207). Interacts with TP53BP1 (via the Tudor-like domain); interaction is abolished following DNA damage and TP53BP1 phosphorylation by ATM (By similarity). Interacts (via the cytoplasmic part) with SDC4 (PubMed:11805099). Interacts with TGFB1I1 and PXN (PubMed:11805099).|||Key regulator of TP53BP1 required to stabilize TP53BP1 and regulate its recruitment to chromatin. In absence of DNA damage, interacts with the tandem Tudor-like domain of TP53BP1, masking the region that binds histone H4 dimethylated at 'Lys-20' (H4K20me2), thereby preventing TP53BP1 recruitment to chromatin and maintaining TP53BP1 localization to the nucleus. Following DNA damage, ATM-induced phosphorylation of TP53BP1 and subsequent recruitment of RIF1 leads to dissociate NUDT16L1/TIRR from TP53BP1, unmasking the tandem Tudor-like domain and allowing recruitment of TP53BP1 to DNA double strand breaks (DSBs). Binds U8 snoRNA.|||Nucleus http://togogenome.org/gene/10090:Rfx4 ^@ http://purl.uniprot.org/uniprot/Q7TNK1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc, detected in most of the neural plate but is excluded from the presumptive forebrain region. At 9.5 dpc, its expression is mostly restricted to two large regions, the caudal diencephalon/mesencephalon and the spinal cord. By 10.5 dpc, is present throughout the neural tube, and it is also detected in the cerebral cortex. It is also strongly expressed in the developing subcommissural organ (SCO) from 14.5 dpc to birth.|||Belongs to the RFX family.|||Homodimer. Heterodimer with RFX2 and RFX3. Binds DNA (By similarity). Interacts with GPS2 (PubMed:18218630).|||Induced in a subjective night-specific manner.|||Isoform 1: Brain-specific. Isoform 2: Testis-specific. Isoform 1: Highly expressed in the suprachiasmatic nucleus, the central pacemaker site of the circadian clock (at protein level).|||Mice with an insertion of a cardiac-specific epoxygenase transgene into an intron in the Rfx4 locus develop head swelling and rapid neurological decline in young adulthood, and have marked hydrocephalus of the lateral and third ventricles. Interruption of two alleles results in profound failure of dorsal midline brain structure formation and perinatal death. Interruption of a single allele prevents formation of the subcommissural organ, a structure important for cerebrospinal fluid flow through the aqueduct of Sylvius and results in congenital hydrocephalus.|||Nucleus|||Transcription factor that plays a role in early brain development. May activate transcription by interacting directly with the X-box. May activate transcription from CX3CL1 promoter through the X-box during brain development. http://togogenome.org/gene/10090:Slc16a7 ^@ http://purl.uniprot.org/uniprot/O70451|||http://purl.uniprot.org/uniprot/Q149G3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Cytoplasm|||Detected in testis and in spermatozoa (at protein level).|||Homodimer (By similarity). Interacts with GRID2IP (PubMed:17496809). Interacts with EMB; interaction mediates SLC16A7 targeting to the plasma membrane (By similarity). Interacts with isoform 2 of BSG (PubMed:21792931).|||Lateral cell membrane|||Membrane|||Proton-coupled monocarboxylate symporter (PubMed:21792931). Catalyzes the rapid transport across the plasma membrane of monocarboxylates such as L-lactate, pyruvate and ketone bodies, acetoacetate, beta-hydroxybutyrate and acetate. Dimerization is functionally required and both subunits work cooperatively in transporting substrate (By similarity).|||Transport activity exhibits steep dependence on substrate concentration. Substrate concentration sensitivity of SLC16A7 arises from the strong inter-subunit cooperativity of the SLC16A7 dimer during transport. Inhibited by AR-C155858. http://togogenome.org/gene/10090:Areg ^@ http://purl.uniprot.org/uniprot/P31955|||http://purl.uniprot.org/uniprot/Q4FJT2 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Androgen-dependent.|||Belongs to the amphiregulin family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Ligand of the EGF receptor/EGFR. Autocrine growth factor as well as a mitogen for a broad range of target cells including astrocytes, Schwann cells and fibroblasts.|||Membrane|||The immature precursor interacts with CNIH. http://togogenome.org/gene/10090:Kctd9 ^@ http://purl.uniprot.org/uniprot/Q80UN1 ^@ Function|||Subunit ^@ Forms pentamers. Component of a complex mades of five KCTD9 and five CUL3 subunits.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome. http://togogenome.org/gene/10090:Ano3 ^@ http://purl.uniprot.org/uniprot/A2AHL1 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide (PubMed:23532839). Does not exhibit calcium-activated chloride channel (CaCC) activity (PubMed:23532839). Seems to act as potassium channel regulator and may inhibit pain signaling; can facilitate KCNT1/Slack channel activity by promoting its full single-channel conductance at very low sodium concentrations and by increasing its sodium sensitivity (PubMed:23872594).|||In the developing gastrointestinal tract, expressed in the intestinal epithelium at 14.5 dpc and in an incomplete ring of cells in the mesenchyme of the esophagus, stomach and small intestine at 16.5 dpc. In the developing skeleton, expressed in the perichondria of the neural arch of developing vertebrae at 14.5 dpc and 16.5 dpc. At 14.5 dpc, also expressed in perichondria of developing ribs. At 14.5 dpc and 16.5 dpc, detected in dorsal root ganglia and neural tube. In developing skin, expression is detected in the most suprabasal layers at 16.5 dpc. Not detected in the lung at 14.5 dpc or 16.5 dpc.|||Interacts with KCNT1/Slack.|||Predominantly expressed in neuronal tissues. Expressed in brain.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Sh3pxd2b ^@ http://purl.uniprot.org/uniprot/A0A5F8MPP7|||http://purl.uniprot.org/uniprot/A2AAY5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. Plays a role in mitotic clonal expansion during the immediate early stage of adipocyte differentiation.|||Belongs to the SH3PXD2 family.|||Cytoplasm|||Exhibit skeletal, cardiac and eye phenotypes. Mice have glaucoma and suffer growth retardation as well as craniofacial defects. Skeletons show marked kyphosis, poorly aligned teeth, anomalies in the iliac crest, and a prominent xiphisternum. Mice show loss of adipose tissue as well as cardiac deficiencies, such as dysmorphic ventricular chambers, thin mitral valves and immature and disarrayed trabeculae with frequent apical indentation. Mice show loss of ROS formation.|||Expression increases quickly after induction of adipocyte differentiation, reaches a maximum after 3 hours and decreases by 12 hours. Expressed from embryonic day 10.5 dpc in heart and hindbrain, followed by an increased expression at 12.5 dpc that also involves a subset of cells on the luminal side of the left ventricular wall in the case of the heart and neuroepithelium in the case of the brain. At 14.5 dpc, expression is present in developing bones (proximal ribs, lower jaw and clavicle), but the expression in the heart is no longer detectable. At stages 16.5 dpc and 18.5 dpc, strong expression is seen in the long bones of the limbs, particularly in the growth plates, as well as in the facial and cranial bones and the primordial incisor. Expression in the ribs is seen in the proximal regions in those areas where the transition from cartilage to bone is expected to occur. Expression in the eye at 16.5 dpc is highly specific for the ganglion cell layer.|||Highly expressed in the stromal-vascular fraction of white adipose tissue with moderate expression in heart, skeletal muscle and the mature adipocyte fraction of white adipose tissue. Also expressed in brain, spleen, kidney and liver. Expressed in white and brown adipose tissues, eye, lung, heart, brain, spleen, stomach, liver and skeletal muscle (at protein level). Not expressed in kidney or bone marrow.|||Interacts with NOXO1 (By similarity). Interacts (via SH3 domains) with NOXA1; the interaction is direct (By similarity). Interacts with ADAM15. Interacts with FASLG (By similarity).|||Phosphorylated in SRC-transformed cells.|||The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity).|||podosome http://togogenome.org/gene/10090:Vps13a ^@ http://purl.uniprot.org/uniprot/Q5H8C4|||http://purl.uniprot.org/uniprot/Q6P6M9 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS13 family.|||Endoplasmic reticulum membrane|||Endosome membrane|||Golgi apparatus|||Interacts (via FFAT motif) with VAPA and VAPB (By similarity). Interacts with RAB7A (By similarity). Interacts with XK (By similarity).|||Intron retention.|||Lipid droplet|||Lysosome membrane|||Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Required for the formation or stabilization of ER-mitochondria contact sites which enable transfer of lipids between the ER and mitochondria (By similarity). Negatively regulates lipid droplet size and motility (By similarity). Required for efficient lysosomal protein degradation (By similarity).|||Mice show defects in motor coordination, social investigation, erythrocyte morphology as well as size and morphology of the striatum. Provides a mouse model for chorea-acanthocytosis (CHAC) with a mild phenotype and late adult onset.|||Mitochondrion outer membrane|||The C-terminal part (3050-3166) is involved in phospholipid binding, including phosphatidylinositol 4,5-bisphosphate.|||The FFAT motif is required for interaction with VAPA and VAPB and its localization to the endoplasmic reticulum.|||neuronal dense core vesicle http://togogenome.org/gene/10090:Rnase2a ^@ http://purl.uniprot.org/uniprot/Q8K196 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Carmil3 ^@ http://purl.uniprot.org/uniprot/Q3UFQ8 ^@ Domain|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CARMIL family.|||Cell membrane|||Cytoplasm|||The C-terminus is necessary for localization to the cell membrane.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:Smtn ^@ http://purl.uniprot.org/uniprot/Q921U8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the smoothelin family.|||Structural protein of the cytoskeleton.|||cytoskeleton http://togogenome.org/gene/10090:Per2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0U3|||http://purl.uniprot.org/uniprot/O54943|||http://purl.uniprot.org/uniprot/Q3TW41|||http://purl.uniprot.org/uniprot/Q8C8R0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated (PubMed:18662546, PubMed:30782483). Deacetylated by SIRT1, resulting in decreased protein stability (PubMed:18662546). Deacetylated by SIRT6, preventing its degradation by the proteasome, resulting in increased protein stability (PubMed:30782483).|||Animals show severely disrupted circadian behavior. During myocardial ischemia, they have larger infarct sizes with deficient lactate production. Mice show reduced muscle strength under stress conditions, show endothelial dysfunctions and have a mean arterial pressure significantly lower compared to wild types. They have elevated circulatory insulin levels associated with enhanced glucose-stimulated insulin secretion and impaired insulin clearance. Animals also have increased levels of liver glycogen and impaired hepatic gluconeogenesis. They display altered lipid metabolism with drastic reduction of total triacylglycerides and non-esterified fatty acids. Double knockouts for PER2 and PER1 show an abrupt loss of rhythmicity immediately upon transfer to exposure to constant darkness. Animals have largely affected the water intake (polydipsia) and urine volume (polyuria). Double knocknouts for PER2 and PER3 show the same phenotype as PER2 simple knockouts. Double knockout for NR1D1 and PER2 show a significantly shorter period length compared with wild type or single knockouts for both genes. 50% of double knockouts animals show a stable circadian throughout at least 5 weeks in constant darkness. The other 50% of animals lose their circadian rhythmicity when held in constant darkness for an average of 21 days. Animals have blunted steady-state levels of glycogen in the liver in spite of normal patterns of food consumption.|||Cytoplasm|||Expressed in the SCN during late fetal and early neonatal life. Expression increases during adipogenesis.|||Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:11779462). Interacts with CLOCK-BMAL1 (off DNA). Interacts with BMAL2. Interacts directly with PER1 and PER3, and through a C-terminal domain, with CRY1 and CRY2. Interacts (via PAS 2 domain) with TIMELESS. Interacts with NFIL3. Different large complexes have been identified with different repressive functions. The core of PER complexes is composed of at least PER1, PER2, PER3, CRY1, CRY2, CSNK1D and/or CSNK1E. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex. Interacts with SETX; the interaction inhibits termination of circadian target genes. Interacts with the nuclear receptors HNF4A, NR1D1, NR4A2, RORA, PPARA, PPARG and THRA; the interaction with at least PPARG is ligand dependent. Interacts with PML. Interacts (phosphorylated) with BTRC and FBXW11; the interactions trigger proteasomal degradation. Interacts with NONO and SFPQ. Interacts with CAVIN3. Interacts with MAGEL2. Interacts with MAP1LC3B (PubMed:29937374). Interacts with HNF4A (By similarity).|||In the brain, high expression in SCN during the subjective day. Constitutive expression in the cornu ammonis and in the dentate gyrus of the hippocampus. Also expressed in the piriform cortex and the glomeruli of the olfactory bulb, and at a lower extent in the cerebral cortex. Not expressed in the pars tuberalis and the Purkinje neurons. Also expressed in adipose tissue (white and brown), heart, kidney, bladder, lumbar spinal cord, skeletal muscle, spleen, lung, pancreas and liver with highest levels in skeletal muscle and liver and lowest levels in spleen.|||Nucleus|||Oscillates diurnally in several tissues, mainly in central nervous system and liver (at protein levels) but also in pancreas, bladder and lumbar spinal cord. Rhythmic levels are critical for the generation of circadian rhythms in central as well as peripheral clocks. Targeted degradation of PER and CRY proteins enables the reactivation of CLOCK-BMAL1, thus initiating a new circadian transcriptional cycle with an intrinsic period of 24 hours.|||Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in PER2 protein degradation. May be dephosphorylated by PP1.|||Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndrome and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors. PER appears to regulate circadian control of transcription by at least three different modes. First, interacts directly with the CLOCK-BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription. Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1. The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases. Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-BMAL1 interactions. Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. May propagate clock information to metabolic pathways via the interaction with nuclear receptors. Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like BMAL1 or G6PC1. Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby transcriptional activation. Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels. Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas. Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression. May also be involved in the regulation of inflammatory processes. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1.|||Ubiquitinated, leading to its proteasomal degradation. Ubiquitination may be inhibited by CRY1.|||perinuclear region http://togogenome.org/gene/10090:Or7d10 ^@ http://purl.uniprot.org/uniprot/Q8VEY9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Imp4 ^@ http://purl.uniprot.org/uniprot/Q8VHZ7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Component of a heterotrimeric complex containing IMP3, IMP4 and MPHOSPH10. Interacts with MPHOSPH10.|||nucleolus http://togogenome.org/gene/10090:Tfpi ^@ http://purl.uniprot.org/uniprot/O54819|||http://purl.uniprot.org/uniprot/Q8BSB7 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma (By similarity).|||Isoform alpha is expressed in heart and spleen; isoform beta in heart and lung.|||Secreted|||This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa (By similarity). http://togogenome.org/gene/10090:Heatr5a ^@ http://purl.uniprot.org/uniprot/Q5PRF0 ^@ Similarity ^@ Belongs to the HEATR5 family. http://togogenome.org/gene/10090:Kcnab2 ^@ http://purl.uniprot.org/uniprot/A0A571BF54|||http://purl.uniprot.org/uniprot/P62482|||http://purl.uniprot.org/uniprot/Q3UPV6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shaker potassium channel beta subunit family.|||Cell membrane|||Cytoplasm|||Cytoplasmic potassium channel subunit that modulates the characteristics of the channel-forming alpha-subunits (PubMed:8576199). Contributes to the regulation of nerve signaling, and prevents neuronal hyperexcitability (PubMed:11825900, PubMed:21209188). Promotes expression of the pore-forming alpha subunits at the cell membrane, and thereby increases channel activity (By similarity). Promotes potassium channel closure via a mechanism that does not involve physical obstruction of the channel pore (PubMed:8576199). Modulates the functional properties of KCNA4 (By similarity). Modulates the functional properties of KCNA5 (PubMed:8576199). Enhances KCNB2 channel activity (PubMed:8824288). Modulates the functional properties of KCNA5 (PubMed:8576199). Binds NADPH and has NADPH-dependent aldoketoreductase activity (By similarity). Has broad substrate specificity and can catalyze the reduction of methylglyoxal, 9,10-phenanthrenequinone, prostaglandin J2, 4-nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-trans-2-nonenal (in vitro) (By similarity).|||Detected in brain (PubMed:21357749). Detected at basket cell terminals in cerebellum and in the juxtaparanodal region of nodes of Ranvier (at protein level) (PubMed:11825900, PubMed:26269648). Strongest expression in brain and eye. Highest levels in brain detected in brainstem and diencephalon. Strong expression also detected in lung and heart. Moderate expression in kidney, T-lymphocytes and skeletal muscle.|||Homotetramer (By similarity). Interaction with tetrameric potassium channel alpha subunits gives rise to a heterooctamer (By similarity). Identified in potassium channel complexes containing KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNAB1 and KCNAB2 (By similarity). Interacts with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Interacts with KCNA4 and KCND3 (By similarity). Interacts (in unphosphorylated form) with MAPRE1 (By similarity). Interacts with KCNA5 (PubMed:8576199, PubMed:8824288). Interacts with KCNB2 (PubMed:8824288). Forms a ternary complex with SQSTM1 and PRKCZ (By similarity).|||In contrast to KCNAB1, the shorter N-terminal domain of KCNAB2 cannot mediate closure of delayed rectifier potassium channels by physically obstructing the pore.|||Membrane|||Mutant mice are born at the expected Mendelian rate and are fertile, but exhibit occasional seizures and have a median lifespan of 255 days, which is much shorter than the 400 days typically observed for heterozygotes (PubMed:11825900). The reduction in lifespan depends strongly on the genetic background; median survival is 138 days for B6 mice, 255 days for B6/129 mice and over 400 days for 129/SvEv mice (PubMed:15720404). Mice exhibit whole body tremors after swimming in cold water, which is not observed in wild-type (PubMed:11825900). The whole body tremors observed after swimming in cold water differ between mouse strains; the observed differences are largely due to differences in the decrease of the core body temperature (PubMed:15720404). Mice lacking both KCNAB1 and KCNAB2 have a median survival of 114 days instead of the 255 days observed for mice lacking only KCNAB2, but show no aggravation of the whole body tremors observed after swimming in cold water (PubMed:15720404). Mice lacking KCNAB2 show subtle deficits in associative learning and aberrant excitability of neurons from the lateral amygdala (PubMed:21209188).|||Not detected prior to birth, low levels of expression detected from postnatal days 1 to 7. Expression reaches adult levels by postnatal day 21.|||Phosphorylated by PRKCZ; may be regulated by incorporation in a complex composed of PRKCZ and SQSTM1.|||axon|||cytoskeleton|||synaptosome http://togogenome.org/gene/10090:Nfu1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SUH8|||http://purl.uniprot.org/uniprot/Q9QZ23 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NifU family.|||Iron-sulfur cluster scaffold protein which can assemble [4Fe-4S] clusters and deliver them to target proteins.|||Mitochondrion|||Monomer and homohexamer; the apo-NFU1 is a monomer, while the holo-NFU1 is a hexamer composed of a trimer of dimer that is probably linked by some 4Fe-4S cluster. Interacts with HIRA and EPM2A/laforin. Interacts with BOLA3. Interacts with HSPA9.|||cytosol http://togogenome.org/gene/10090:Zfp74 ^@ http://purl.uniprot.org/uniprot/Q80W31 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Wnt7a ^@ http://purl.uniprot.org/uniprot/P24383 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Wnt family.|||Defects in Wnt7a cause the postaxial hemimelia (px) phenotype that is characterized by limb patterning defects accompanied by Mullerian duct-associated sterility in both sexes.|||Detected in the flanking ectoderm of the trunk prior to limb outgrowth. First detected in the presumptive forelimb region at 8.75 dpc, and in the presumptive hindlimb region at 9.25 dpc. Uniformly distributed throughout the dorsal limb ectoderm during the initial stages of limb-bud outgrowth (9.25 dpc for the forelimbs, 9.75 dpc for the hindlimbs).|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (By similarity). The complex with AFM may represent the physiological form in body fluids (By similarity). Interacts with FZD5 (PubMed:18230341, PubMed:20530549). Interacts with PORCN (PubMed:10866835). Interacts (via intrinsically disordered linker region) with RECK; interaction with RECK confers ligand selectivity for Wnt7 in brain endothelial cells and allows these cells to selectively respond to Wnt7 (By similarity).|||Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:18230341, PubMed:20530549, PubMed:23629626). Plays an important role in embryonic development, including dorsal versus ventral patterning during limb development, skeleton development and urogenital tract development (PubMed:7885472, PubMed:9769174, PubMed:9790192). Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (PubMed:28803732). Required for normal, sexually dimorphic development of the Mullerian ducts, and for normal fertility in both sexes (PubMed:9790192). Required for normal neural stem cell proliferation in the hippocampus dentate gyrus (PubMed:23629626). Required for normal progress through the cell cycle in neural progenitor cells, for self-renewal of neural stem cells, and for normal neuronal differentiation and maturation (PubMed:23629626). Promotes formation of synapses via its interaction with FZD5 (PubMed:20530549).|||Male mice lacking Wnt7a fail to undergo regression of the Mullerian duct as a result of the absence of the receptor for Mullerian-inhibiting substance. In males, mature sperm fills the vas deferens, but sperm exit is blocked due to the persistence of the Mullerian duct, causing male sterility. Wnt7a deficient females are infertile because of abnormal development of the oviduct and uterus, both of which are Mullerian duct derivatives.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||The intrinsically disordered linker region is required for recognition by RECK in brain endothelial cells.|||extracellular matrix http://togogenome.org/gene/10090:Cdc20b ^@ http://purl.uniprot.org/uniprot/D3Z3I0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the WD repeat CDC20/Fizzy family.|||Cytoplasm|||Expressed in multiciliated cells (MCCs).|||Protein regulator of centriole-deuterosome disengagement and subsequently participates in the ciliogenesis in multiciliated cells (MCCs). http://togogenome.org/gene/10090:Glipr1l2 ^@ http://purl.uniprot.org/uniprot/Q9CQ35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CRISP family.|||Membrane http://togogenome.org/gene/10090:Arhgef11 ^@ http://purl.uniprot.org/uniprot/Q68FM7 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Membrane http://togogenome.org/gene/10090:Ssc4d ^@ http://purl.uniprot.org/uniprot/A1L0T3 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Pramel45 ^@ http://purl.uniprot.org/uniprot/A0A571BEB1 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Tmed7 ^@ http://purl.uniprot.org/uniprot/D3YZZ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the EMP24/GP25L family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Membrane|||cis-Golgi network membrane http://togogenome.org/gene/10090:Hsd11b2 ^@ http://purl.uniprot.org/uniprot/P51661 ^@ Activity Regulation|||Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the conversion of biologically active 11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as corticosterone, to inactive 11-ketoglucocorticoids (11-oxosteroid) such as 11-dehydrocorticosterone, in the presence of NAD(+) (Probable) (PubMed:30902677, PubMed:22796344). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids (PubMed:7664690). Plays an important role in maintaining glucocorticoids balance during preimplantation and protects the fetus from excessive maternal corticosterone exposure (PubMed:31600723). Catalyzes the oxidation of 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a major bioactive androgen (PubMed:22796344). Catalyzes the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be further metabolized to 11-ketotestosterone (By similarity). Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro (By similarity). 7-beta-25-dihydroxycholesterol (not 7-oxo-25-hydroxycholesterol) acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration (By similarity).|||Endoplasmic reticulum|||Expression (mRNA and protein) is highest in uteri on days 3 and 4 during early pregnancy.|||Highly expressed in kidney (PubMed:7664690). Also found in colon and small intestine (PubMed:7664690). Not expressed in the adrenal gland (PubMed:7664690). Expressed in uterus (PubMed:31600723).|||Inhibited by glycyrrhetinic acid (By similarity). Induced by progesterone, through the Ihh signaling pathway (PubMed:31600723).|||Interacts with ligand-free cytoplasmic NR3C2.|||Microsome|||Rats and mice do not produce appreciable cortisol, because they do not express the 17-alpha hydroxylase (Cyp17a1) enzyme in the adrenals. http://togogenome.org/gene/10090:Zbed3 ^@ http://purl.uniprot.org/uniprot/Q9D0L1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a positive regulator in the activation of the canonical Wnt/beta-catenin signaling pathway by stabilizing cytoplasmic beta-catenin (PubMed:19141611). Involved in transcription activation of Wnt target gene expression (PubMed:19141611). Plays a role in symmetric division of blastomeres in the early stages of embryogenesis via regulation of mitotic spindle central positioning and organization of the F-actin filament network (PubMed:28992324). Plays a role in regulating the distribution of cellular organelles, via modulation of cytoskeletal dynamics and cytoplasmic lattice formation (PubMed:28992324).|||Associates with the subcortical maternal complex (SCMC) composed of at least NLRP5, KHDC3, OOEP, and TLE6 via interaction with NLRP5 and TLE6 (PubMed:28992324, PubMed:31575650). Interacts (via PPPSP motif) with AXIN1; the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations (PubMed:19141611).|||Cytoplasm|||Dual phosphorylation on serine and tyrosine residues of the cytoplasmic PPPSP motif by GSK3 and CK1 may be required for AXIN1-binding.|||Expressed in the cytoplasm of germinal vesicle oocytes before becoming concentrated in the subcortex of metaphase 2 oocytes (PubMed:28992324). Expressed in ovaries at birth, expression peaks at postnatal day 10 (P10), expression is then decreased at P17 and further decreased at P21 (PubMed:31575650).|||Expressed in the liver (at protein level) (PubMed:24283382). Abundantly expressed in muscle, with lower expression in brain, fat, and heart (PubMed:24283382). Expressed in the spleen, lungs and kidney (PubMed:24283382, PubMed:28992324). Abundantly expressed in ovaries and testis, with lower expression in the uterus (PubMed:28992324).|||Males show normal fertility however females produce smaller litters (PubMed:28992324). Increase in the number of 2-cell embryos with asymmetric blastomeres as a result of impaired central mitotic spindle position and therefore an increase in the distance between the cellular center and the chromosomes (PubMed:28992324). Disorganization of the F-actin filament network around the mitotic spindle and loss of FMN2-expressing endoplasmic reticulum localization to the mitotic spindle periphery in zygotes and oocytes (PubMed:28992324). Mitochondria are mislocalized to the plus-ends of elongated microtubules in the subcortical cytoplasm in oocytes prior to nuclear envelope breakdown (PubMed:28992324). Loss of cytoplasmic lattices and extension of the alpha-tubulin pool into the subcortical region following microtubule-organizing center congression in oocytes (PubMed:28992324).|||Membrane|||Secreted http://togogenome.org/gene/10090:Tomt ^@ http://purl.uniprot.org/uniprot/A1Y9I9 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Absence of auditory brain stem response (ABR) to click stimuli demonstrates that the mice are profoundly deaf. Normal hair bundle morphology as at postnatal day (P) 5 the sensory epithelia are patterned into three rows of outer hair cells (OHCs) and one row of inner hair cells (IHCs). The bundles of OHCs appear similar in size to those of wild-type mice and form a normal staircase pattern. Hair cells are maintained in the presence of gentamicin, an aminoglycoside antibiotic that enters hair cells through their transduction channels and normally causes hair cell death. No difference in the expression or localization of tip link proteins CDH23 and PCDH15 or ATP2B2, MYO7A, ESPN and WHRN proteins at P5-P8 in hair bundles of hair cells. Normal localization of LHFPL5 and TMIE in OHCs, but TMC1 and TMC2 are absent from the hair bundles of OHCs.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.|||Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones (PubMed:18794526). Required for auditory function (PubMed:18794526, PubMed:28504928). Component of the cochlear hair cell's mechanotransduction (MET) machinery. Involved in the assembly of the asymmetric tip-link MET complex. Required for transportation of TMC1 and TMC2 proteins into the mechanically sensitive stereocilia of the hair cells. The function in MET is independent of the enzymatic activity (PubMed:28504928).|||Cytoplasm|||Despite its name, the murine TOMT protein does not contain a transmembrane region in contrast to primate orthologs.|||Endoplasmic reticulum|||Interacts with LHFPL5, PCDH15, TMC1, TMC2 and TMIE (PubMed:28504928). The interaction of TOMT with TMC1 and TMC2 is required for the transportation of TMC1/2 into the stereocilia of hair cells (PubMed:28504928, PubMed:28534737). Interacts directly with TMC1 (PubMed:28534737).|||Not detected in the embryo at 12.5 dpc. At 14.5 dpc, expressed in the developing inner ear. At 16.5 dpc, expressed in the utricle and saccule. At 18.5 dpc, expressed specifically in the region of the sensory cells of the cochlea, utricle, saccule and crista ampullaris.|||Widely expressed with high levels in outer and inner hair cells of the cochlea and vestibule. http://togogenome.org/gene/10090:Aldh1b1 ^@ http://purl.uniprot.org/uniprot/Q9CZS1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (By similarity).|||Belongs to the aldehyde dehydrogenase family.|||Homotetramer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Gpr151 ^@ http://purl.uniprot.org/uniprot/Q7TSN6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||High expression in the brain and lower levels in kidney and liver (PubMed:14667573). In the nervous system expressed specifically in the habenular area (at protein level) (PubMed:25116430).|||High levels detected at 7 dpc.|||Proton-sensing G-protein coupled receptor. http://togogenome.org/gene/10090:Fat1 ^@ http://purl.uniprot.org/uniprot/A0A087WRT4|||http://purl.uniprot.org/uniprot/A0A1L1SQU7|||http://purl.uniprot.org/uniprot/F2Z4A3 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Wnt5b ^@ http://purl.uniprot.org/uniprot/P22726 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Wnt family.|||Interacts with PORCN.|||Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||extracellular matrix http://togogenome.org/gene/10090:Ovca2 ^@ http://purl.uniprot.org/uniprot/Q9D7E3 ^@ Caution|||Developmental Stage|||Similarity|||Tissue Specificity ^@ Belongs to the LovG family.|||Encoded in an intron of the gene DPH1/OVCA1 (same strand).|||Expressed in embryonic stem (ES) cells.|||Strongly expressed in kidney and liver. Moderately expressed in brain, skin and testis. Weakly expressed in heart, lung, small intestine, spleen, stomach and thymus. http://togogenome.org/gene/10090:Map2 ^@ http://purl.uniprot.org/uniprot/P20357|||http://purl.uniprot.org/uniprot/Q3TLQ0|||http://purl.uniprot.org/uniprot/Q80ZL4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with KNDC1 (via KIND2); the interaction enhances MAP2 phosphorylation and localizes KNDC1 to dendrites. Interacts with DPYSL5 (By similarity).|||Phosphorylated at serine residues in K-X-G-S motifs by causing MAP/microtubule affinity-regulating kinase (MARK1 or MARK2), detachment from microtubules, and their disassembly (By similarity). The interaction with KNDC1 enhances MAP2 threonine phosphorylation (PubMed:17984326).|||The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules.|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Adamts5 ^@ http://purl.uniprot.org/uniprot/Q8BGP4|||http://purl.uniprot.org/uniprot/Q9R001 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Expressed in skeletal muscle.|||Expressed specifically in the peri-implantation period in embryo and trophoblast and at low or undetectable level thereafter (PubMed:10464288). In embryonic skeletal muscle, levels significantly increase between 13.5 dpc and 15.5 dpc with maximal expression observed at 15.5 dpc (PubMed:23233679). Decreased levels in postnatal skeletal muscle (PubMed:23233679). In myoblasts, up-regulated soon after induction of myoblast differentiation (PubMed:23233679).|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Metalloproteinase that plays an important role in connective tissue organization, development, inflammation and cell migration. Extracellular matrix (ECM) degrading enzyme that shows proteolytic activity toward the hyalectan group of chondroitin sulfate proteoglycans (CSPGs) including ACAN, VCAN, BCAN and NCAN. Cleavage within the hyalectans occurs at Glu-Xaa recognition motifs. Plays a role in embryonic development, including limb and cardiac morphogenesis, and skeletal muscle development through its VCAN remodeling properties. Cleaves VCAN in the pericellular matrix surrounding myoblasts, facilitating myoblast contact and fusion which is required for skeletal muscle development and regeneration (PubMed:23233679). Participates in the development of brown adipose tissue and browning of white adipose tissue (PubMed:28702327). Plays an important role for T-lymphocyte migration from draining lymph nodes following viral infection (PubMed:27855162).|||Mice are viable and fertile (PubMed:15800625). Significantly increased mass of brown adipose tissue (PubMed:28702327). Delayed virus clearance and compromised T cell migration during viral infection (PubMed:27855162). No effect on VCAN cleavage in embryonic skeletal muscle, potentially as a result of participation by other proteinases, but absence of VCAN cleavage and greater number of centrally located nuclei in postnatal skeletal muscle (PubMed:23233679).|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by furin and PCSK7 outside of the cell.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Ino80 ^@ http://purl.uniprot.org/uniprot/Q6ZPV2 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATPase component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and DNA repair. Binds DNA. As part of the INO80 complex, remodels chromatin by shifting nucleosomes. Regulates transcription upon recruitment by YY1 to YY1-activated genes, where it acts as an essential coactivator. Involved in UV-damage excision DNA repair. The contribution to DNA double-strand break repair appears to be largely indirect through transcriptional regulation. Involved in DNA replication. Required for microtubule assembly during mitosis thereby regulating chromosome segregation cycle.|||Activated upon binding to double stranded DNA or nucleosomes.|||Belongs to the SNF2/RAD54 helicase family.|||Chromosome|||Component of the chromatin remodeling INO80 complex; three different complex modules assemble on different domains of INO80. Interacts with DDB1. Interacts with transcriptional repressor protein YY1; the interaction recruits the INO80 complex to YY1 target genes. Interacts with YY1AP1. Interacts with tubulin alpha.|||Cytoplasm|||Nucleus|||The DBINO region is involved in binding to DNA.|||Widely expressed.|||spindle http://togogenome.org/gene/10090:Rdx ^@ http://purl.uniprot.org/uniprot/P26043|||http://purl.uniprot.org/uniprot/Q3TH46|||http://purl.uniprot.org/uniprot/Q7TSG6 ^@ Activity Regulation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding.|||Cell membrane|||Cleavage furrow|||Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (PubMed:12522145). Binds NHERF1 (By similarity). Interacts with LAYN (PubMed:15913605). Interacts with NHERF1 and NHERF2 (PubMed:16615918). Interacts with MME/NEP (PubMed:17459884). Interacts with ICAM2 (PubMed:12554651, PubMed:9472040). Interacts (via FERM domain) with SPN/CD43 cytoplasmic tail (PubMed:9472040, PubMed:18614175). Interacts with CD44 (PubMed:9472040).|||Membrane|||Phosphorylated by tyrosine-protein kinases. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding.|||Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.|||The N-terminal domain interacts with the C-terminal domain of LAYN. An interdomain interaction between its N-terminal and C-terminal domains inhibits its ability to bind LAYN. In the presence of acidic phospholipids, the interdomain interaction is inhibited and this enhances binding to LAYN.|||cytoskeleton|||microvillus http://togogenome.org/gene/10090:Ccl6 ^@ http://purl.uniprot.org/uniprot/P27784 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Associated with stimuli that promote myeloid differentiation.|||Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic factor that attracts mostly macrophage, but it can also attract B cells, CD4(+) lymphocytes and eosinophils.|||Expressed in myelopoietic bone marrow cultures stimulated by GM-CSF.|||Secreted|||The N-terminal is proteolytically cleaved by proteases associated with inflammatory responses. The processed forms CL6(22-95) and CCL6(23-95) show increase in CCR1-mediated signaling and chemotaxis assays in vitro. http://togogenome.org/gene/10090:Emg1 ^@ http://purl.uniprot.org/uniprot/O35130|||http://purl.uniprot.org/uniprot/Q542P8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase NEP1 family.|||Homodimer. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||S-adenosyl-L-methionine-dependent pseudouridine N(1)-methyltransferase that methylates pseudouridine at position in 18S rRNA. Involved the biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA. Is not able to methylate uridine at this position (By similarity). Has also an essential role in 40S ribosomal subunit biogenesis independent on its methyltransferase activity, facilitating the incorporation of ribosomal protein S19 during the formation of pre-ribosomes (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||nucleolus http://togogenome.org/gene/10090:Vmn1r94 ^@ http://purl.uniprot.org/uniprot/K7N6X3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fmnl3 ^@ http://purl.uniprot.org/uniprot/D3Z7A7|||http://purl.uniprot.org/uniprot/Q6ZPF4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the formin homology family.|||Cell membrane|||Cytoplasm|||Interacts with SRGAP2 (via SH3 domain).|||Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Required for developmental angiogenesis. In this process, required for microtubule reorganization and for efficient endothelial cell elongation. In quiescent endothelial cells, triggers rearrangement of the actin cytoskeleton, but does not alter microtubule alignement.|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity). http://togogenome.org/gene/10090:Prss27 ^@ http://purl.uniprot.org/uniprot/Q8BJR6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Secreted http://togogenome.org/gene/10090:Ebp ^@ http://purl.uniprot.org/uniprot/P70245 ^@ Disease Annotation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the EBP family.|||Binds to the phenylalkylamine calcium-ion antagonist emopamil, an anti-ischemic drug.|||Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.|||Cytoplasmic vesicle|||Defects in Ebp are a cause of 'Tattered' (Td) which is an X-linked, semidominant mouse mutation associated with prenatal male lethality. Heterozygous females are small and at 4 to 5 days of age develop patches of hyperkeratotic skin where no hair grows, resulting in a striping of the coat in adults. Craniofacial anomalies and twisted toes have also been observed in some affected females.|||Endoplasmic reticulum membrane|||Nucleus envelope http://togogenome.org/gene/10090:Vmn1r139 ^@ http://purl.uniprot.org/uniprot/E9Q8L6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mapk8ip1 ^@ http://purl.uniprot.org/uniprot/Q3UI81|||http://purl.uniprot.org/uniprot/Q6GQW8|||http://purl.uniprot.org/uniprot/Q9WVI9 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JIP scaffold family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed predominantly in the brain and insulin-secreting cells. In the brain, high expression found in the cerebral cortex and hippocampus. Localizes in the synaptic regions of the olfactory bulb, retina, cerebral and cerebellar cortex and hippocampus. Also expressed in a restricted number of axons, including mossy fibers from the hippocampal dentate gyrus, soma, dendrites and axons of cerebellar Purkinje cells. Also expressed in kidney, testis and prostate. Low levels in heart, ovary and small intestine. Isoform JIP-1b is more predominant in the brain than isoform JIP-1a. Isoform Jip1-a is expressed both in the brain and kidney, isoform JIP-1c, isoform JIP-1d and isoform JIP-1e are brain specific.|||Forms homo- or heterooligomeric complexes. Binds specific components of the JNK signaling pathway namely MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAP2K7/MKK7, MAP3K11/MLK3 and DLK1. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2) (By similarity). Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of kinesin light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location. Interacts with the cytoplasmic domain of APP (By similarity). Interacts, via the PID domain, with ARHGEF28. Interacts with MAP3K7/TAK1 and VRK2 (By similarity). Interacts with DCLK2 (PubMed:16628014). Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1 (PubMed:23963642). Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103). Interacts with SH3RF2 (By similarity).|||Low levels at prenatal stage 15 dpc, increased levels during the first postnatal days, with a plateau at postnatal day 15.|||Mitochondrion membrane|||Nucleus|||Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr-103 is also necessary for the dissociation and activation of MAP3K12. Phosphorylated by VRK2. Hyperphosphorylated during mitosis following activation of stress-activated and MAP kinases (By similarity).|||The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and thus inhibiting the JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response (By similarity). Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8(+) T-cells (PubMed:23963642).|||The SH3 domain mediates homodimerization.|||Ubiquitinated. Two preliminary events are required to prime for ubiquitination; phosphorylation and an increased in intracellular calcium concentration. Then, the calcium influx initiates ubiquitination and degradation by the ubiquitin-proteasome pathway.|||Upon neuron differentiation.|||perinuclear region http://togogenome.org/gene/10090:Prss30 ^@ http://purl.uniprot.org/uniprot/Q9QYZ9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Expressed primarily in distal gut.|||Inhibited by aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor. Partially inhibited by PMSF and DFP (By similarity).|||Selectively cleaves synthetic peptide substrates of trypsin. Activates the epithelial sodium channel ENaC (By similarity). http://togogenome.org/gene/10090:Nup188 ^@ http://purl.uniprot.org/uniprot/Q6ZQH8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Nup188 family.|||Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Required for proper protein transport into the nucleus.|||Part of the nuclear pore complex (NPC).|||nuclear pore complex http://togogenome.org/gene/10090:Fam187b ^@ http://purl.uniprot.org/uniprot/Q0VAY3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM187 family.|||Membrane http://togogenome.org/gene/10090:Snx18 ^@ http://purl.uniprot.org/uniprot/Q8C788 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||Cytoplasmic vesicle membrane http://togogenome.org/gene/10090:Lnpep ^@ http://purl.uniprot.org/uniprot/Q8C129 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Endomembrane system|||Homodimer. Binds tankyrases 1 and 2 (By similarity).|||Release of an N-terminal amino acid, cleave before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain (By similarity). http://togogenome.org/gene/10090:Prss36 ^@ http://purl.uniprot.org/uniprot/D3YV46|||http://purl.uniprot.org/uniprot/E9QJT0 ^@ Function|||Subcellular Location Annotation ^@ Serine protease. Has a preference for substrates with an Arg instead of a Lys residue in position P1.|||extracellular matrix http://togogenome.org/gene/10090:Pds5a ^@ http://purl.uniprot.org/uniprot/E9QPI5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PDS5 family.|||Nucleus http://togogenome.org/gene/10090:Cabcoco1 ^@ http://purl.uniprot.org/uniprot/Q8CDT7 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium-binding protein (PubMed:26990073). May be involved in the control of sperm flagellar movement (PubMed:26990073).|||Cytoplasm|||Testis-specific (PubMed:26990073). Expressed in spermatocytes and round spermatids (at protein level) (PubMed:26990073).|||centrosome|||flagellum http://togogenome.org/gene/10090:Cplx1 ^@ http://purl.uniprot.org/uniprot/P63040 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the complexin/synaphin family.|||Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.|||In the brain, expression starts at P6 and increases to reach a plateau at P20.|||Mice have no obvious brain abnormality, but suffer from severe ataxia with dystonia starting from P7. Adult mice lacking Cplx1 are not capable of coordinated running or swimming and exhibit pronounced resting tremor. They also fail to habituate to confinement and have reduced exploration abilities in open field.|||Nervous system, and pancreatic islet cells. Present in many brain regions, including hippocampus and cerebellum. In the retina, present at conventional amacrine cell synapses (at protein level).|||Perikaryon|||Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles (PubMed:23345244). Organizes the SNAREs into a cross-linked zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion, thereby preventing SNAREs from releasing neurotransmitters until an action potential arrives at the synapse (PubMed:23345244). Also involved in glucose-induced secretion of insulin by pancreatic beta-cells. Essential for motor behavior (PubMed:15126625, PubMed:16000319).|||Presynapse|||cytosol http://togogenome.org/gene/10090:Frmpd1 ^@ http://purl.uniprot.org/uniprot/A2AKB4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with GPSM1 (By similarity). Interacts with GPSM2 (PubMed:23318951).|||Stabilizes membrane-bound GPSM1, and thereby promotes its interaction with GNAI1.|||cytosol http://togogenome.org/gene/10090:Fam210a ^@ http://purl.uniprot.org/uniprot/Q8BGY7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM210 family.|||Cytoplasm|||Embryonic lethality in homozygotes mice after embryonic day 9.5 (PubMed:29618611). Tamoxifen-inducible Fam210a homozygous knockout mice exhibit decreased grip strength, lean mass of all limbs, bone mineral density, bone biomechanical strength, and elevated osteoclast activity with microarchitectural deterioration of trabecular and cortical bones (PubMed:29618611).|||Expressed in skeletal muscle, heart, brain but not in bone.|||Interacts with ATAD3A.|||May play a role in the structure and strength of both muscle and bone.|||Membrane|||Mitochondrion http://togogenome.org/gene/10090:Cenpp ^@ http://purl.uniprot.org/uniprot/Q9CZ92 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-P/CTF19 family.|||Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex (By similarity).|||Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (By similarity).|||Nucleus|||centromere http://togogenome.org/gene/10090:Trim37 ^@ http://purl.uniprot.org/uniprot/Q6PCX9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the PRC2/EED-EZH2 complex.|||Auto-ubiquitinated.|||Belongs to the TRIM/RBCC family.|||Chromosome|||E3 ubiquitin-protein ligase required to prevent centriole reduplication (By similarity). Probably acts by ubiquitinating positive regulators of centriole reduplication (By similarity). Mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression: associates with some Polycomb group (PcG) multiprotein PRC2-like complex and mediates repression of target genes (PubMed:25470042). Also acts as a positive regulator of peroxisome import by mediating monoubiquitination of PEX5 at 'Lys-472': monoubiquitination promotes PEX5 stabilitation by preventing its polyubiquitination and degradation by the proteasome (By similarity).|||Highly expressed in testis and brain. In embryonic tissues, expressed in epithelia, including ducts of the developing pancreas, epithelium of the midgut and nasal epithelium. In adult, detected in the central and peripheral nervous systems, including enteric ganglia, retina and the adrenal medulla (at protein level).|||Peroxisome membrane|||perinuclear region http://togogenome.org/gene/10090:Sfxn2 ^@ http://purl.uniprot.org/uniprot/Q3UC14|||http://purl.uniprot.org/uniprot/Q925N2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sideroflexin family.|||Expressed in brain, heart, kidney, spleen, thymus, liver, stomach and skin.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mitochondrial amino-acid transporter that mediates transport of serine into mitochondria (By similarity). Involved in mitochondrial iron homeostasis by regulating heme biosynthesis (By similarity).|||Mitochondrion inner membrane|||Mitochondrion membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Brwd3 ^@ http://purl.uniprot.org/uniprot/A2AHJ4 ^@ Function ^@ Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity). http://togogenome.org/gene/10090:Or10g1b ^@ http://purl.uniprot.org/uniprot/E9PWU0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pnliprp1 ^@ http://purl.uniprot.org/uniprot/Q5BKQ4 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Expressed in female, but not in male, lacrimal gland. Expressed in male and female sublingual gland and pancreas.|||Expression is gender and species-specific.|||May function as inhibitor of dietary triglyceride digestion. Lacks detectable lipase activity (in vitro) (By similarity).|||Mice have no visible phenotype during the first 10 weeks after birth and are fertile. Adult mice have normal body weight, but higher than normal body fat and lower than normal lean mass. They display impaired glucose tolerance and decreased insulin sensitivity, and obesity and insulin resistance are exacerbated by high-fat diet. Their pancreatic juice has greater ability to hydrolyze triglycerides than that from wild-type littermates.|||Secreted http://togogenome.org/gene/10090:Vmn2r37 ^@ http://purl.uniprot.org/uniprot/F8VQD3|||http://purl.uniprot.org/uniprot/O35202 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Reg4 ^@ http://purl.uniprot.org/uniprot/Q9D8G5 ^@ Function|||Subcellular Location Annotation ^@ Calcium-independent lectin displaying mannose-binding specificity and able to maintain carbohydrate recognition activity in an acidic environment. May be involved in inflammatory and metaplastic responses of the gastrointestinal epithelium (By similarity).|||Secreted http://togogenome.org/gene/10090:Krt222 ^@ http://purl.uniprot.org/uniprot/Q8CCX5 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Bmp3 ^@ http://purl.uniprot.org/uniprot/A0A0G2JEU2|||http://purl.uniprot.org/uniprot/Q149J9|||http://purl.uniprot.org/uniprot/Q8BHE5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adult mice lacking BMP3 have increased bone mass (PubMed:11138004). Targeted loss of BMP3 results also in increased differentiation of early osteoblasts precursors into mature osteoblasts and further supports a role of BMP3 in regulating adult bone mass (PubMed:22074949).|||Belongs to the TGF-beta family.|||Homodimer.|||Homodimer; disulfide-linked.|||Negatively regulates bone density. Antagonizes the ability of certain osteogenic BMPs to induce osteoprogenitor differentiation and ossification.|||Secreted http://togogenome.org/gene/10090:Zfp488 ^@ http://purl.uniprot.org/uniprot/Q5HZG9 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Detected in differentiated oligodendrocytes, from embryos at 14.5 dpc through to the postnatal stage.|||Interacts with OLIG2.|||Nucleus|||Transcriptional repressor (PubMed:16908628). Plays a role in oligodendrocyte differentiation, together with OLIG2 (PubMed:16908628, PubMed:22355521). Mediates Notch signaling-activated formation of oligodendrocyte precursors (PubMed:16908628). Promotes differentiation of adult neural stem progenitor cells (NSPCs) into mature oligodendrocytes and contributes to remyelination following nerve injury (PubMed:22355521).|||Up-regulated by OLIG1. http://togogenome.org/gene/10090:Papola ^@ http://purl.uniprot.org/uniprot/E9PZR3|||http://purl.uniprot.org/uniprot/Q3V141|||http://purl.uniprot.org/uniprot/Q61183 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated in the C-terminus. Acetylation decreases interaction with NUDT21 and KPNB1, and inhibits nuclear localization through inhibiting binding to the importin alpha/beta complex (By similarity).|||Belongs to the poly(A) polymerase family.|||Binds 2 magnesium ions. Also active with manganese.|||Expressed in brain, thymus, lung, kidney, bladder, testis and spleen.|||Hyperphosphorylation on multiple CDK2 consensus and non-consensus sites in the C-terminal Ser/Thr-rich region represses PAP activity in late M-phase. Phosphorylation/dephosphorylation may regulate the interaction between PAP and CPSF (By similarity).|||Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with AHCYL1 and FIP1L1; the interaction with AHCYL1 seems to increase interaction with FIP1L1 (PubMed:19224921). Interacts with NUDT21; the interaction is diminished by acetylation. Interacts with KPNB1; the interaction promotes PAP nuclear import and is inhibited by acetylation of PAP (By similarity).|||Nucleus|||Polymerase that creates the 3'-poly(A) tail of mRNA's.|||Polymerase that creates the 3'-poly(A) tail of mRNA's. Also required for the endoribonucleolytic cleavage reaction at some polyadenylation sites. May acquire specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus.|||Polysumoylated. Varying sumoylation depending on tissue- and cell-type. Highly sumoylated in bladder and NIH 3T3 cells. Sumoylation is required for nuclear localization and enhances PAP stability. Desumoylated by SENP1. Inhibits polymerase activity. http://togogenome.org/gene/10090:Ctcfl ^@ http://purl.uniprot.org/uniprot/A2APF3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CTCF zinc-finger protein family.|||Cytoplasm|||Interacts with histones, PRMT7 and SETD1A. Interacts (via N-terminus) with BAG6/BAT3 (By similarity).|||Not detected at 13.5 dpc. Detected in mitotically arrested gonocytes of 14.5 dpc embryos. From 17.5 dpc to newborn, it is expressed in some centrally located gonocytes and cells present at the periphery of the developing seminiferous tubules. Present in nuclei of spermatogonia from 15 days after birth to adulthood.|||Nucleus|||Testis-specific DNA binding protein responsible for insulator function, nuclear architecture and transcriptional control, which probably acts by recruiting epigenetic chromatin modifiers. Plays a key role in gene imprinting in male germline, by participating in the establishment of differential methylation at the IGF2/H19 imprinted control region (ICR). Directly binds the unmethylated H19 ICR and recruits the PRMT7 methyltransferase, leading to methylate histone H4 'Arg-3' to form H4R3sme2. This probably leads to recruit de novo DNA methyltransferases at these sites. Seems to act as tumor suppressor. In association with DNMT1 and DNMT3B, involved in activation of BAG1 gene expression by binding to its promoter. Required for dimethylation of H3 lysine 4 (H3K4me2) of MYC and BRCA1 promoters.|||Testis-specific. http://togogenome.org/gene/10090:Arid3c ^@ http://purl.uniprot.org/uniprot/A6PWV5|||http://purl.uniprot.org/uniprot/B7ZP08 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer.|||Nucleus|||Transcription factor. http://togogenome.org/gene/10090:Pcdhga9 ^@ http://purl.uniprot.org/uniprot/Q91XX9 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Sec61g ^@ http://purl.uniprot.org/uniprot/G3UWH0|||http://purl.uniprot.org/uniprot/P60060|||http://purl.uniprot.org/uniprot/Q5SWJ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SecE/SEC61-gamma family.|||Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides (By similarity). The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex (By similarity). The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER (By similarity).|||Endoplasmic reticulum membrane|||Membrane|||The SEC61 channel-forming translocon complex consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63 (By similarity). The SEC61 channel associates with the multi-pass translocon (MPT) complex (By similarity). http://togogenome.org/gene/10090:Ndrg1 ^@ http://purl.uniprot.org/uniprot/Q545R3|||http://purl.uniprot.org/uniprot/Q62433 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NDRG family.|||Cell membrane|||In early stages of embryo development, expression low when MYCN expression is high. Later, when MYCN levels diminish, levels increase.|||Interacts with RAB4A (membrane-bound form); the interaction involves NDRG1 in vesicular recycling of CDH1. Interacts with APOA1, APOA2, PRA1 and RTN1 (By similarity).|||Mutant mice exhibit defects in peripheral nerve development. Initial hind limb weakness developed around age 12 weeks, and significant functional impairment (dragging of hind legs) and muscle atrophy became apparent at age 1 year. After about 5 weeks extensive demyelination of nerve fibers is observed. In later life, large inclusions were seen in the adaxonal Schwann cell cytoplasm. There is no evidence of apoptotic response.|||Nucleus|||Repressed by testosterone and also to a lesser extent by dihydrotestosterone. Down-regulated by MYCN.|||Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy (By similarity). Has a role in cell trafficking notably of the Schwann cell and is necessary for the maintenance and development of the peripheral nerve myelin sheath.|||Under stress conditions, phosphorylated in the C-terminal on many serine and threonine residues. Phosphorylated in vitro by PKA. Phosphorylation enhanced by increased intracellular cAMP levels. Homocysteine induces dephosphorylation. Phosphorylation by SGK1 is cell cycle dependent (By similarity).|||Widely expressed, with highest levels in kidney followed by brain, pancreas, small intestine, colon and spleen (at protein level). Also detected in heart and preputial gland, and in much smaller quantities in other tissues. Not detected in duodenum and prostate. Highly expressed in Schwann cells.|||centrosome|||cytosol http://togogenome.org/gene/10090:Or5p54 ^@ http://purl.uniprot.org/uniprot/Q8VFC9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Ms4a4d ^@ http://purl.uniprot.org/uniprot/Q99N05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed in thymus, spleen, peripheral lymph node, liver, kidney, heart, colon, lung, and testes.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Asah2 ^@ http://purl.uniprot.org/uniprot/B9EHG7|||http://purl.uniprot.org/uniprot/Q9JHE3 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neutral ceramidase family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Golgi apparatus membrane|||Homozygous knockout mice have a normal life span and do not show obvious abnormalities or major alterations in total ceramide levels in tissues (PubMed:16380386). However, they are deficient in the intestinal digestion of dietary ceramides (PubMed:16380386). A decrease in total ceramides in liver is also observed (PubMed:21613224).|||Inhibited by D-erythro-MAPP.|||May interact with CAV1.|||Membrane raft|||Mitochondrion|||N-glycosylated. Required for enzyme activity.|||O-glycosylated. Required to retain it as a type II membrane protein at the cell surface.|||Phosphorylated. May prevent ubiquitination and subsequent degradation.|||Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH (PubMed:10753931, PubMed:10652340, PubMed:16380386). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:14557071). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (PubMed:10652340, PubMed:21613224). Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin, a sphingolipid enriched in the plasma membrane of cells (PubMed:16126722). Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells (PubMed:16126722). This is the case for instance with the digestion of dietary sphingolipids in the intestinal tract (PubMed:16380386).|||Proteolytic cleavage of the N-terminus removes the signal-anchor and produces a soluble form of the protein.|||Secreted|||Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxide.|||Widely expressed (PubMed:10753931, PubMed:14557071). Strongly expressed in small intestine and to a lower extent in liver and kidney (PubMed:10753931). Highly expressed in duodenum, jejunum and ileum along the brush border of the small intestine (at protein level) (PubMed:16380386).|||caveola|||extracellular exosome http://togogenome.org/gene/10090:Zfand3 ^@ http://purl.uniprot.org/uniprot/Q497H0 ^@ Developmental Stage|||Tissue Specificity ^@ Expressed in testis.|||Preferentially expressed during the haploid stages of spermatogenesis. http://togogenome.org/gene/10090:Pdilt ^@ http://purl.uniprot.org/uniprot/Q9DAN1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum|||Homodimer. The homodimer is not disulfide-linked. Interacts with CLGN and ERO1A (By similarity).|||N-glycosylated.|||Probable redox-inactive chaperone involved in spermatogenesis.|||Testis-specific (at protein level).|||The thioredoxin domain lacks the conserved redox-active Cys at position 414 which is replaced by a Ser residue, suggesting that it lacks thioredoxin activity. http://togogenome.org/gene/10090:Ror2 ^@ http://purl.uniprot.org/uniprot/Q8C3W2 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Garnl3 ^@ http://purl.uniprot.org/uniprot/Q3V0G7 ^@ Similarity ^@ Belongs to the GARNL3 family. http://togogenome.org/gene/10090:Eddm13 ^@ http://purl.uniprot.org/uniprot/E9Q7F5 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Highly expressed in segments II-V of the caput epididymis.|||Secreted http://togogenome.org/gene/10090:Cd200r2 ^@ http://purl.uniprot.org/uniprot/Q6XJV6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ According to PubMed:15187158 it is a receptor for the CD200 cell surface glycoprotein. According to PubMed:16081818 it is not a receptor for the CD200/OX2 cell surface glycoprotein. Involved in the recruitment or surface expression of the TYROBP receptor.|||Belongs to the CD200R family.|||Expressed in bone marrow, spleen, brain, lung, testis and thymus.|||Membrane http://togogenome.org/gene/10090:Rlim ^@ http://purl.uniprot.org/uniprot/Q9WTV7 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNF12 family.|||E3 ubiquitin-protein ligase that acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes in somatic cells of female placental mammals.|||Expressed at higher level in female compared to males cells (at protein level).|||Interacts (via N-terminus) with TERF1. Interacts (via C-terminus) with ESR1 (By similarity). Interacts with LIM/homeobox factors such as LHX3. Interacts with LDB1, LDB2 and SIN3A. Interacts with LIMK1.|||Nucleus|||Ubiquitously expressed in early development. Expressed in the time window of embryonic stem (ES) cell differentiation. http://togogenome.org/gene/10090:Tbc1d5 ^@ http://purl.uniprot.org/uniprot/Q80XQ2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endosome membrane|||Interacts with MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1, GABARAPL2. Interacts with VPS29 and VPS35; indicative for an association with retromer CSC subcomplex. MAP1LC3A and VPS29 compete for binding to TBC1D5. Interacts with AP2M1; indicative for an association with the AP2 complex. Interacts with ULK1 and ATG13 (phosphorylated); indicative for an association with the activated ULK1-ATG13-FIP200 complex. Interacts with ATG9A; the interactions seems to be restricted to the AP2-clathrin-associated fraction of ATG9A.|||May act as a GTPase-activating protein for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity. Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy. May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (By similarity).|||The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. LIR 1 is also implicated in interaction with retromer; LIR 2 is only implicated in interaction with ATG8 family proteins.|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.|||autophagosome http://togogenome.org/gene/10090:Cep72 ^@ http://purl.uniprot.org/uniprot/Q9D3R3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP72 family.|||Interacts with KIZ, PCM1 and CDK5RAP2.|||Involved in the recruitment of key centrosomal proteins to the centrosome. Provides centrosomal microtubule-nucleation activity on the gamma-tubulin ring complexes (gamma-TuRCs) and has critical roles in forming a focused bipolar spindle, which is needed for proper tension generation between sister chromatids. Required for localization of KIZ, AKAP9 and gamma-tubulin ring complexes (gamma-TuRCs) (By similarity). Involved in centriole duplication. Required for CDK5RAP22, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (By similarity).|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||centriolar satellite|||centrosome http://togogenome.org/gene/10090:Atpsckmt ^@ http://purl.uniprot.org/uniprot/Q9D1Z3 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ANT/ATPSC lysine N-methyltransferase family.|||Contains an atypical, non-cleavable mitochondrial targeting sequence responsible for its localization to mitochondria.|||Expression is up-regulated in dorsal root ganglia (DRG) during chronic inflammatory pain.|||Mitochondrial protein-lysine N-methyltransferase that trimethylates ATP synthase subunit C, ATP5MC1 and ATP5MC2. Trimethylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration (PubMed:29444090, PubMed:30530489). Promotes chronic pain (PubMed:29444090). Involved in persistent inflammatory and neuropathic pain: methyltransferase activity in the mitochondria of sensory neurons promotes chronic pain via a pathway that depends on the production of reactive oxygen species (ROS) and on the engagement of spinal cord microglia (PubMed:29444090).|||Mitochondrion membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Ephb3 ^@ http://purl.uniprot.org/uniprot/P54754 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Expressed during development in yolk sacs and by embryonic endothelial cells. Expressed in the developing intestinal epithelium at the bottom of the intervillus pockets where undifferentiated cells are allocated (at protein level). In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912).|||Expressed in cells of the retinal ganglion cell layer during retinal axon guidance to the optic disk. Expressed by Paneth and progenitor cells in the crypts of the intestinal epithelium (at protein level). Expressed in myogenic progenitor cells (PubMed:27446912).|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity).|||Mice are viable and fertile and show no obvious abnormal behavior. The corpus callosum, the main axon tract connecting the left and right cerebral hemispheres, is not formed in a significant fraction of newborns. This is associated with defects in guidance of callosal axons across the midline.|||Phosphorylated. Autophosphorylates upon ligand-binding. Autophosphorylation on Tyr-609 is required for interaction with SH2 domain-containing proteins (By similarity).|||Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt.|||Ubiquitinated by RNF186, mainly through 'Lys-48' and 'Lys-63'-linked polyubiquitin chains.|||dendrite http://togogenome.org/gene/10090:Fundc1 ^@ http://purl.uniprot.org/uniprot/H3BJ77|||http://purl.uniprot.org/uniprot/H3BJZ1|||http://purl.uniprot.org/uniprot/Q9DB70 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control.|||Belongs to the FUN14 family.|||Interacts (via YXXL motif) with MAP1 LC3 family proteins MAP1LC3A, MAP1LC3B and GABARAP.|||Mitochondrion outer membrane|||Phosphorylation at Tyr-18 by SRC inhibits activation of mitophagy. Following hypoxia, dephosphorylated at Tyr-18, leading to interaction with MAP1 LC3 family proteins and triggering mitophagy (By similarity).|||The YXXL motif mediates the interaction with MAP1 LC3 family proteins MAP1LC3A, MAP1LC3B and GABARAP. http://togogenome.org/gene/10090:Il34 ^@ http://purl.uniprot.org/uniprot/Q8R1R4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-34 family.|||Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of pro-inflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1 (By similarity).|||Homodimer. Interacts with CSF1R (By similarity).|||Secreted http://togogenome.org/gene/10090:Tesc ^@ http://purl.uniprot.org/uniprot/Q9JKL5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According PubMed:22285131, mice show a normal number of megakaryocytes and platelets.|||Belongs to the calcineurin regulatory subunit family. CHP subfamily.|||Binds calcium via its EF-hands. Calcium-binding mediates a conformational change. Can also bind magnesium.|||Cell membrane|||Cytoplasm|||Expressed in embryonic, newborn and adult testis, but not in prepubertal testis. Expressed in the embryonic testis during testis determination but is not expressed at any time in the embryonic ovary. In embryonic testis, expression is restricted to the testis cords and is seen in both Sertoli cells and germ cells. Expression is excluded from the myoid cells which surround the cords. Expressed in the embryonic adrenal after the initial stages of differentiation. Expressed at a lower level in the embryonic brain, heart and lung but not in liver or gut. May be expressed at a very low level in the embryonic kidney. In the embryonic brain, expressed in the nasal placode and in fibers extending from the olfactory epithelium to the primordial olfactory bulb. In adults, expressed in the heart, and weakly in the brain and kidney. Highly expressed in terminally differentiated megakaryocytes (at protein level). Not detected in fetal liver cells (at protein level).|||Expression is first detected in the male gonad at 11.5 dpc, peaks at 14.5 dpc, declines slightly by 15.5 dpc, and continues to at least 17.5 dpc.|||Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Promotes the maturation, transport, cell surface stability and exchange activity of SLC9A1/NHE1 at the plasma membrane. Promotes the induction of hematopoietic stem cell differentiation toward megakaryocytic lineage. Essential for the coupling of ERK cascade activation with the expression of ETS family genes in megakaryocytic differentiation. Also involved in granulocytic differentiation in a ERK-dependent manner. Inhibits the phosphatase activity of calcineurin.|||Membrane|||Monomer (PubMed:14661968). Homodimer; disulfide-linked (PubMed:14661968). Interacts with SLC9A1/NHE1; the interaction enables an optimal Na(+)/H(+) exchange activity (By similarity).|||Nucleus|||The region of SLC9A1/NHE1 that interacts with CHP3 is conflicting: In human, interaction with SLC9A1/NHE1 has been reported via residues 507-549, the juxtamembrane region of the cytoplasmic C-terminus. However, another publication has reported interaction with SLC9A1/NHE1 via residues 637-820, the region of the cytoplasmic C-terminus more distal to the membrane.|||lamellipodium|||ruffle membrane http://togogenome.org/gene/10090:Tmem205 ^@ http://purl.uniprot.org/uniprot/Q91XE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM205 family.|||Membrane http://togogenome.org/gene/10090:Tnp1 ^@ http://purl.uniprot.org/uniprot/P10856|||http://purl.uniprot.org/uniprot/Q545L6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Appears in elongating/condensing spermatids when histones are still detectable (PubMed:15163613). Coexpressed with H2ab1 during late spermiogenesis (PubMed:28366643).|||Belongs to the nuclear transition protein 1 family.|||Chromosome|||Nucleus|||Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals (PubMed:10781074, PubMed:15163613, PubMed:15189834, PubMed:15083521, PubMed:28366643). In condensing spermatids, loaded onto the nucleosomes, where it promotes the recruitment and processing of protamines, which are responsible for histone eviction (PubMed:28366643). The histone H2AB1-H2BC1/TH2B dimer is required for loading of TNP1 onto chromatin (PubMed:28366643).|||Reduced fertility in males (PubMed:10781074). Testis weights and sperm production are normal but sperm motility is severely reduced (PubMed:10781074). A significant proportion of Prm2 remains unprocessed (PubMed:10781074, PubMed:15163613, PubMed:15189834, PubMed:15083521). Male mice lacking both Tnp1 and Tnp2 are completely infertile, but protamine alone are capable of histone eviction (PubMed:15163613, PubMed:15189834, PubMed:15083521). Chromatin in mature spermatozoa shows defects in density (PubMed:15189834, PubMed:15083521).|||Testis-specific. http://togogenome.org/gene/10090:Casz1 ^@ http://purl.uniprot.org/uniprot/Q9CWL2 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the brain stem and the thalamencephalon.|||First expressed at 8.0 dpc in the developing heart and throughout development. By 8.5 dpc, it is expressed in the lateral neural folds of the hindbrain and extends anteriorly and posteriorly to eventually cover the dorsal neural tube from the isthmus to its caudal end. From 9.5 dpc, it is expressed in the dorsomedial telencephalon. In the hindbrain, it is confined to trigeminal motor neurons and to migrating facial branchiomotor neurons. In the peripheral nervous system, it is expressed in cranial and in dorsal root ganglia. Also expressed in the developing eye and in the nasal placode.|||Nucleus|||Transcription factor involved in vascular assembly and morphogenesis through direct transcriptional regulation of EGFL7.|||Up-regulated during myoblast differentiation. http://togogenome.org/gene/10090:Cct8 ^@ http://purl.uniprot.org/uniprot/P42932|||http://purl.uniprot.org/uniprot/Q3UL22|||http://purl.uniprot.org/uniprot/Q8BVY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG (By similarity). Interacts with DNAAF4 (PubMed:23872636).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Tmem39b ^@ http://purl.uniprot.org/uniprot/Q810L4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM39 family.|||Endoplasmic reticulum membrane|||May protect the cells against DNA damage caused by exposure to the cold-warming stress and facilitates tissue damage repair during the recovery phase. http://togogenome.org/gene/10090:Aloxe3 ^@ http://purl.uniprot.org/uniprot/Q14B96|||http://purl.uniprot.org/uniprot/Q9WV07 ^@ Caution|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||Cytoplasm|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice die within 5 to 12 hours after birth due to defective skin barrier function loosing around 2.5% of body weight per hour. Dehydratation through the skin is increased 4 folds. The outside-in barrier acquisition is also affected, the skin remaining permeable at 18.5 dpc while it is impermeable in wild-type mice. The stratum corneum is more tightly packed while other layers are unaffected. Hyperkeratosis of the skin is observed but it is not associated with defects in epidermal differentiation while the ceramide composition of the epidermis is altered with an absence of ester-bound ceramides.|||Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced lipoxygenases activity (PubMed:17045234). The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols and ketones (PubMed:17045234). In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides. In the skin, acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins (By similarity). Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss (PubMed:22832496). In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites (By similarity). Also plays a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG (PubMed:20530198). Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia (By similarity).|||Skin specific. http://togogenome.org/gene/10090:Ces1b ^@ http://purl.uniprot.org/uniprot/D3Z5G7 ^@ Similarity ^@ Belongs to the type-B carboxylesterase/lipase family. http://togogenome.org/gene/10090:Mgat1 ^@ http://purl.uniprot.org/uniprot/P27808|||http://purl.uniprot.org/uniprot/Q544F0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 13 family.|||Detected in kidney, liver and brain.|||Golgi apparatus membrane|||Initiates complex N-linked carbohydrate formation. Essential for the conversion of high-mannose to hybrid and complex N-glycans.|||Interacts with MGAT4D. Interacts with BRI3 (By similarity).|||Membrane|||The cofactor is mostly bound to the substrate.|||perinuclear region http://togogenome.org/gene/10090:Rpa3 ^@ http://purl.uniprot.org/uniprot/Q9CQ71 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin, in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Also plays a role in base excision repair (BER), probably through interaction with UNG. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance. RPA3 has its own single-stranded DNA-binding activity and may be responsible for polarity of the binding of the complex to DNA.|||Belongs to the replication factor A protein 3 family.|||Component of the canonical replication protein A complex (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3. Also a component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2 (By similarity).|||Nucleus|||Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination. http://togogenome.org/gene/10090:Tspan17 ^@ http://purl.uniprot.org/uniprot/Q3TAQ3|||http://purl.uniprot.org/uniprot/Q9D7W4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Interacts with ADAM10.|||Membrane|||Regulates ADAM10 maturation. http://togogenome.org/gene/10090:Or5w22 ^@ http://purl.uniprot.org/uniprot/Q7TR48 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:S1pr2 ^@ http://purl.uniprot.org/uniprot/P52592 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Most abundant in heart and lung; low, but clearly observed in kidney, liver and thymus; much lower but detectable in brain, testis, stomach and intestine. Not significantly detected in any of the sections of embryonic day (E) 14-18, except in embryonic brain.|||Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P) (By similarity). S1P is a bioactive lysophospholipid that elicits diverse physiological effects on most types of cells and tissues (By similarity). Receptor for the chemokine-like protein FAM19A5 (By similarity). Mediates the inhibitory effect of FAM19A5 on vascular smooth muscle cell proliferation and migration (By similarity). http://togogenome.org/gene/10090:Scamp2 ^@ http://purl.uniprot.org/uniprot/Q3TAL2|||http://purl.uniprot.org/uniprot/Q3TU28|||http://purl.uniprot.org/uniprot/Q9ERN0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCAMP family.|||Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface (By similarity).|||Interacts with SLC6A4 and SLC9A7. Interacts with SLC9A5; this interaction regulates SLC9A5 cell-surface targeting and SLC9A5 activity.|||Membrane|||Recycling endosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:H1f7 ^@ http://purl.uniprot.org/uniprot/Q8CJI4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the histone H1/H5 family.|||Chromosome|||Essential for normal spermatogenesis and male fertility. Required for proper cell restructuring and DNA condensation during the elongation phase of spermiogenesis. Involved in the histone-protamine transition of sperm chromatin and the subsequent production of functional sperm. Binds both double-stranded and single-stranded DNA, ATP and protamine-1.|||First detected in round spermatids at stage 4 and expression strongly increases through stages 5-8. Localization in the nucleus is highly polar and it is concentrated in a cap-like structure at the inner periphery of the nuclear membrane. Polarized expression persists in steps 9-14 elongating spermatids before rapidly disappearing by stage 15.|||Nucleus|||Testis-specific. Specifically expressed in haploid germ cells. http://togogenome.org/gene/10090:Gcnt4 ^@ http://purl.uniprot.org/uniprot/E9Q649 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 14 family.|||Glycosyltransferase that mediates core 2 O-glycan branching, an important step in mucin-type biosynthesis. Does not have core 4 O-glycan or I-branching enzyme activity.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Vmn2r27 ^@ http://purl.uniprot.org/uniprot/D3YUK6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ighmbp2 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1E3 ^@ Similarity ^@ Belongs to the DNA2/NAM7 helicase family. http://togogenome.org/gene/10090:Gimap7 ^@ http://purl.uniprot.org/uniprot/Q8R379 ^@ Similarity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily. http://togogenome.org/gene/10090:Rnf14 ^@ http://purl.uniprot.org/uniprot/Q9JI90 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RBR family. RNF14 subfamily.|||Cytoplasm|||E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (By similarity). Recruited to stalled ribosomes by the ribosome collision sensor GCN1 and mediates ubiquitination of EEF1A1/eEF1A, leading to its degradation (By similarity). In addition to EEF1A1/eEF1A, RNF14 catalyzes ubiquitination of other translation factors on stalled ribosomes: mediates ubiquitination and degradation of ETF1/eRF1 and ubiquitination of ribosomal proteins RPL0, RPL1, RPL12, RPS13 and RPS17 (By similarity). Independently of its function in the response to stalled ribosomes, acts as a regulator of transcription in Wnt signaling via its interaction with TCF transcription factors (TCF7/TCF1, TCF7L1/TCF3 and TCF7L2/TCF4) (By similarity). May also play a role as a coactivator for androgen- and, to a lesser extent, progesterone-dependent transcription (By similarity). May regulate the expression of both mitochondrial and immune related genes in skeletal muscle (PubMed:24472305).|||Interacts with GCN1; interaction takes place in response to ribosome collisions and is required for ubiquitination of EEF1A1/eEF1A. Interacts with the ubiquitin-conjugating enzymes UBE2E1 and UBE2E2. Interacts with AR/androgen receptor. Interacts with TCF7/TCF1, TCF7L1/TCF3 and TCF7L2/TCF4; promoting Wnt signaling.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.|||Nucleus|||RING-type zinc finger-dependent and UBE2E2-dependent autoubiquitination.|||The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway. http://togogenome.org/gene/10090:Trappc11 ^@ http://purl.uniprot.org/uniprot/B2RXC1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAPPC11 family.|||Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12.|||Golgi apparatus|||Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.|||cis-Golgi network http://togogenome.org/gene/10090:Snx15 ^@ http://purl.uniprot.org/uniprot/Q91WE1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Homodimer. Interacts with SNX1, SNX2 and SNX4 (By similarity).|||May be involved in several stages of intracellular trafficking. Overexpression of SNX15 disrupts the normal trafficking of proteins from the plasma membrane to recycling endosomes or the TGN (By similarity).|||Membrane|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate. http://togogenome.org/gene/10090:Katnbl1 ^@ http://purl.uniprot.org/uniprot/Q9CWJ3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with KATNA1 and KATNAL1; these interactions are competed by KATNB1 which has a higher affinity for them.|||Nucleus|||Regulates microtubule-severing activity of KATNAL1 in a concentration-dependent manner in vitro.|||spindle pole http://togogenome.org/gene/10090:Nudcd2 ^@ http://purl.uniprot.org/uniprot/Q9CQ48 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with LIS1.|||May regulate the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone.|||centrosome|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Pxt1 ^@ http://purl.uniprot.org/uniprot/Q8K459 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ During spermatogenesis, it is first detected in testis at 15 days postpartum (dpp). Expressed at higher level at 17 dpp, 20 dpp, 25 dpp and in adult testis. First expressed when primary spermatocytes are present in postnatal mouse testis.|||Peroxisome|||Testis-specific. http://togogenome.org/gene/10090:Kif7 ^@ http://purl.uniprot.org/uniprot/E9QMU1|||http://purl.uniprot.org/uniprot/J3QNW9 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. http://togogenome.org/gene/10090:Nsun6 ^@ http://purl.uniprot.org/uniprot/A2ASK1|||http://purl.uniprot.org/uniprot/Q7TS68 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.|||Cytoplasm|||S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C5 position of cytosine 72 in tRNA(Thr)(TGT) and tRNA(Cys)(GCA). In vitro also methylates tRNA(Thr)(AGT). Methylation requires, in the acceptor stem region, the presence of the 3'-CCA terminus, the target site C72, the discriminator base U73, and the second and third base pairs (2:71 and 3:70) in the tRNA substrates.|||The PUA domain plays a role in tRNA recognition through precisely recognizing the CCA end and the D-stem region of tRNA. http://togogenome.org/gene/10090:Wfdc3 ^@ http://purl.uniprot.org/uniprot/Q14AE4 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Chmp2b ^@ http://purl.uniprot.org/uniprot/Q8BJF9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF7 family.|||In brain, it is expressed in all neuronal populations with a relatively enhanced expression in the hippocampus, frontal and temporal lobes and in both granule and Purkinje cells of the cerebellum. Not expressed in astrocytes or oligodendrocytes.|||Late endosome membrane|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4 (By similarity).|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with CHMP2A. Interacts with VPS4A. Interacts with VPS4B; the interaction is direct (By similarity).|||cytosol http://togogenome.org/gene/10090:Tor4a ^@ http://purl.uniprot.org/uniprot/Q8BH02 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ClpA/ClpB family. Torsin subfamily.|||Membrane http://togogenome.org/gene/10090:Rasal3 ^@ http://purl.uniprot.org/uniprot/Q8C2K5 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway.|||It is uncertain whether Met-1 or Met-23 is the initiator.|||No visible phenotype. The number of natural killer T (NKT) cells in the liver is selectively decreased (around 50%) in mutant mice (PubMed:25652366).|||Predominantly expressed in hematopoietic tissues.|||cell cortex http://togogenome.org/gene/10090:Kansl1 ^@ http://purl.uniprot.org/uniprot/Q80TG1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.|||Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts with KAT8; the interaction is direct (By similarity).|||Nucleus|||kinetochore http://togogenome.org/gene/10090:Vsnl1 ^@ http://purl.uniprot.org/uniprot/P62761 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the recoverin family.|||Probably binds three calcium ions.|||Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner. http://togogenome.org/gene/10090:Caml ^@ http://purl.uniprot.org/uniprot/P49070 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the Golgi to ER traffic (GET) complex, which is composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40 (By similarity). Within the complex, GET1 and CAMLG form a heterotetramer which is stabilized by phosphatidylinositol binding and which binds to the GET3 homodimer (By similarity). Interacts (via C-terminus) with GET1 (By similarity). Interacts (via N-terminus) with GET3 (By similarity). GET3 shows a higher affinity for CAMLG than for GET1 (By similarity). Interacts (via N-terminus) with TNFRSF13B/TACI (via C-terminus) (By similarity).|||Conditional knockout in B cells results in significant reduction in the number of mature follicular B cells with normal cellular proliferation but increased cellular turnover.|||Endoplasmic reticulum membrane|||Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (By similarity). Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (By similarity). Required for the stability of GET1 (By similarity). Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium (By similarity). Essential for the survival of peripheral follicular B cells (PubMed:22351938). http://togogenome.org/gene/10090:Or4c105 ^@ http://purl.uniprot.org/uniprot/Q8VF98 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Abcb11 ^@ http://purl.uniprot.org/uniprot/Q9QY30 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.|||Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:14570929, PubMed:11172067, PubMed:23764895, PubMed:22619174, PubMed:19228692). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (By similarity). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (By similarity).|||Cell membrane|||Endosome|||Expressed predominantly, if not exclusively in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ.|||Interacts with HAX1 (By similarity). Interacts with the adapter protein complex 2 (AP-2) throught AP2A2 or AP2A1; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (By similarity).|||Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.|||N-glycosylated.|||Recycling endosome membrane|||The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM. Pravastatin competitively inhibits the transport of taurocholic acid. Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate (By similarity). The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content (By similarity) (PubMed:19228692). The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate (By similarity).|||Transgenic mice with up-regulated liver canalicular membrane expression of Abcb11 appear healthy and normal and demonstrate any difference in longevity. Transgenic mice exhibit a normal reproductive rate and gender distribution and are born in a normal Mendelian distribution. Transgenic mice have food consumption identical to their background strain controls. Transgenic mice manifest increases of both bile flow and biliary lipid secretion and are resistant to the development of hepatic steatosis (PubMed:14570929). Homozygous Abcb11 knockout mice on a mixed genetic background are viable and fertile, but displayed growth retardation. Their body weight is about 20% lower than their wild-type littermates at weaning (21 days after birth). They tend to have a lower body weight throughout their life, but display only mild non progressive cholestasis (PubMed:11172067). Homozygous Abcb11 knockout mice on a pure C57BL/6J background exhibit a progressive intrahepatic cholestasis due to an hepatic bile acid retention and an alteration of lipid metabolism (PubMed:22619174).|||Ubiquitinated; short-chain ubiquitination regulates cell-Surface expression of ABCB11. http://togogenome.org/gene/10090:Draxin ^@ http://purl.uniprot.org/uniprot/Q6PAL1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the draxin family.|||Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures. Acts as a chemorepulsive guidance protein for commissural axons during development. Able to inhibit or repel neurite outgrowth from dorsal spinal cord. Inhibits the stabilization of cytosolic beta-catenin (CTNNB1) via its interaction with LRP6, thereby acting as an antagonist of Wnt signaling pathway.|||In embryonic brain, strong expression in the olfactory bulb, anterior olfactory nucleus, neocortex, piriform cortex, glial wedge, midline zipper glia, indusium griseum and the area surrounding the anterior commissure (AC) but not on AC axons (at protein level) (PubMed:23206892). Predominantly expressed in developing neural tissues. Expressed in many brain regions, including the olfactory bulb, cortex, midbrain, cerebellum and pontine nuclei in neonates. Detected in the dorsal spinal cord and commissural axons. In the forebrain commissures, it is expressed in the regions that surround the corpus callosum, hippocampal commissure, and anterior commissure, such as the midline glial cells, indusium griseum glia, and glial wedge.|||Interacts with LRP6.|||Mice are viable and fertile (PubMed:19150847). They however show a defasciculation of spinal cord commissural axons and absence of all forebrain commissures (PubMed:19150847, PubMed:23206892). Double knockout of Tsku and Draxi results in a higher frequency of anterior commissure defects than single knockout of either Tsku or Draxi (PubMed:23206892).|||Secreted http://togogenome.org/gene/10090:Rtn4ip1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0S3|||http://purl.uniprot.org/uniprot/Q924D0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.|||Interacts with RTN4, UQCRC1 and UQCRC2.|||Mitochondrion|||Mitochondrion outer membrane|||Plays a role in the regulation of retinal ganglion cell (RGC) neurite outgrowth, and hence in the development of the inner retina and optic nerve (PubMed:26593267). Appears to be a potent inhibitor of regeneration following spinal cord injury (PubMed:12067236).|||Widely expressed in mitochondria-enriched tissues. Found in heart, kidney, liver, brain and spinal cord. http://togogenome.org/gene/10090:Mep1a ^@ http://purl.uniprot.org/uniprot/A0A0R4J043|||http://purl.uniprot.org/uniprot/P28825 ^@ Activity Regulation|||Caution|||Cofactor|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Homotetramer consisting of disulfide-linked alpha subunits, homooligomer consisting of disulfide-linked alpha subunit homodimers, or heterotetramer of two alpha and two beta subunits formed by non-covalent association of two disulfide-linked heterodimers. Genetic factors determine which oligomer(s) will be formed (strain-specific). Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity.|||Inhibited by metal ion chelators EDTA and 1,10-phenanthroline, bradykinin analogs, cysteine, CONA65, and several hydroxamate compounds, particularly tyrosine hydroxamate. Not inhibited by 3,4-dichloroisocourmarin, soybean trypsin inhibitor, or the cysteine proteinase inhibitors iodoacetic acid and E-64.|||Kidney, intestinal brush borders and salivary ducts.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||N-glycosylated; contains GlcNAc, galactose, mannose and a small amount of fucose. http://togogenome.org/gene/10090:Itga5 ^@ http://purl.uniprot.org/uniprot/P11688|||http://purl.uniprot.org/uniprot/Q80YP5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. ITGA5/Alpha-5 associates with ITGB1/beta-1 (By similarity). Interacts with NISCH (PubMed:11121431, PubMed:14535848, PubMed:15229651). Interacts with HPS5 (By similarity). Interacts with RAB21 and COMP. Interacts with CIB1 (By similarity). ITGA5:ITGB1 interacts with CCN3 (By similarity). ITGA5:ITGB1 interacts with FBN1 (By similarity). ITGA5:ITGB1 interacts with IL1B (By similarity). ITGA5:ITGB1 interacts with ACE2 (By similarity). Interacts with ANGPT2 (By similarity).|||Integrin alpha-5/beta-1 (ITGA5:ITGB1) is a receptor for fibronectin and fibrinogen (PubMed:36812915). It recognizes the sequence R-G-D in its ligands. ITGA5:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1. ITGA5:ITGB1 acts as a receptor for fibronectin (FN1) and mediates R-G-D-dependent cell adhesion to FN1 (By similarity). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling. ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (By similarity).|||Membrane|||Mice die at 10-11 dpc. They show both extraembryonic and embryonic vascular defects, and severe abnormalities in the development of the posterior trunk (PubMed:7508365). Liver-specific mutants show defects specifically in exercise-induced autophagy, but not fasting-induced autophagy, in the liver. Metabolically, after regular diet feeding and 3 weeks of high fat diet (HFD) feeding without exercise, mutants and control mice show comparable body weight gain, glucose tolerance and insulin tolerance. After HFD feeding and daily exercise, they show comparable body weight, exercise endurance and tissue weight. Daily exercise training doesnt't improve glucose tolerance, insulin tolerance and hepatic insulin signaling as it does in control mice (PubMed:36812915).|||Proteolytic cleavage by PCSK5 mediates activation of the precursor.|||focal adhesion http://togogenome.org/gene/10090:Or5m11 ^@ http://purl.uniprot.org/uniprot/Q7TR89 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc25a20 ^@ http://purl.uniprot.org/uniprot/Q9Z2Z6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mediates the electroneutral exchange of acylcarnitines (O-acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)-carnitines) with free carnitine ((R)-carnitine or L-carnitine) across the mitochondrial inner membrane, via a ping-pong mechanism. Key player in the mitochondrial oxidation pathway, it translocates the fatty acids in the form of acylcarnitines into the mitochondrial matrix, where the carnitine palmitoyltransferase 2 (CPT-2) activates them to undergo fatty acid beta-oxidation. Catalyzes the unidirectional transport (uniport) of carnitine at lower rates than the antiport (exchange).|||Mitochondrion inner membrane|||Widely expressed, with highest levels in the liver, intermediate levels in heart, testis and kidney and low levels in brain, including cortex, cerebellum, hippocampus and hypothalamus. http://togogenome.org/gene/10090:Chil1 ^@ http://purl.uniprot.org/uniprot/Q61362 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the glycosyl hydrolase 18 family, Leu-149 is present instead of the conserved Glu which is an active site residue. Therefore this protein lacks chitinase activity.|||Belongs to the glycosyl hydrolase 18 family.|||Carbohydrate-binding lectin with a preference for chitin. Has no chitinase activity. May play a role in tissue remodeling and in the capacity of cells to respond to and cope with changes in their environment. Plays a role in T-helper cell type 2 (Th2) inflammatory response and IL-13-induced inflammation, regulating allergen sensitization, inflammatory cell apoptosis, dendritic cell accumulation and M2 macrophage differentiation. Facilitates invasion of pathogenic enteric bacteria into colonic mucosa and lymphoid organs. Mediates activation of AKT1 signaling pathway and subsequent IL8 production in colonic epithelial cells. Regulates antibacterial responses in lung by contributing to macrophage bacterial killing, controlling bacterial dissemination and augmenting host tolerance. Also regulates hyperoxia-induced injury, inflammation and epithelial apoptosis in lung.|||Cytoplasm|||Detected in lung in pulmonary macrophages and alveolar type 2 cells and in bronchoalveolar lavage (BAL) fluids. Expressed in mammary tumor cells (at protein level). Expressed in lung. Not detected in non-inflammatory colon.|||Endoplasmic reticulum|||May be produced by alternative splicing of isoform 1.|||Mice are viable, fertile and appear normal, but have defective antigen-induced Th2 inflammatory responses and defective IL-13-induced responses, displaying accelerated cell death responses and diminished M2 macrophage differentiation. Mutant mice are more sensitive to S.pneumoniae infection, displaying enhanced mortality, exacerbated lung injury and decreased bacterial clearance compared to wild-type mice. Mutant mice also have an exacerbated response to hyperoxia, displaying enhanced protein leak, tissue inflammation and chemokine production and premature death.|||Monomer.|||Produced by alternative initiation at Met-9 of isoform 1.|||Up-regulated in colon under several inflammatory conditions. Up-regulated upon pulmonary inflammation elicited by sensitization and challenge with the chitin-free aeroallergen ovalbumin or with chitin-containing antigen house dust mite (HDM) extract. Up-regulated in lungs after S.pneumoniae infection. Up-regulated in splenic cells of mammary tumor-bearing animals. Down-regulated by hyperoxia in lung.|||extracellular space http://togogenome.org/gene/10090:Spata31 ^@ http://purl.uniprot.org/uniprot/E9QAF0|||http://purl.uniprot.org/uniprot/Q3V0C6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPATA31 family.|||Interacts with ACTB and STX1A and/or STX1B.|||May play a role in spermatogenesis.|||Membrane|||acrosome lumen|||acrosome membrane http://togogenome.org/gene/10090:Gm5347 ^@ http://purl.uniprot.org/uniprot/Q7M765 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Eif2s2 ^@ http://purl.uniprot.org/uniprot/Q3ULL5|||http://purl.uniprot.org/uniprot/Q99L45 ^@ Function|||Similarity|||Subunit ^@ Belongs to the eIF-2-beta/eIF-5 family.|||Component of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B.|||eIF2 is an heterotrimer composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (EIF2S3) chain (PubMed:16931514). eIF2 is member of the 43S pre-initiation complex (43S PIC). eIF2 forms a complex with at least CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (PubMed:16931514). Interacts with BZW2/5MP1 (By similarity). Interacts with EIF5 (By similarity). http://togogenome.org/gene/10090:Or1e25 ^@ http://purl.uniprot.org/uniprot/Q7TRX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cfap276 ^@ http://purl.uniprot.org/uniprot/Q9DAD0 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||May play an important role for the maintenance of myelin-axon integrity (PubMed:31199454). May affect intracellular Ca(2+) homeostasis.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). May play an important role for the maintenance of myelin-axon integrity (PubMed:31199454). May affect intracellular Ca(2+) homeostasis (By similarity).|||Predominantly expressed in nervous system tissues, such as the spinal cord, cerebrum, cerebellum, and sciatic nerve.|||cilium axoneme|||cytoskeleton http://togogenome.org/gene/10090:Clec3a ^@ http://purl.uniprot.org/uniprot/Q9EPW4 ^@ Function|||Subcellular Location Annotation ^@ Promotes cell adhesion to laminin and fibronectin.|||Secreted http://togogenome.org/gene/10090:Serpinf1 ^@ http://purl.uniprot.org/uniprot/P97298 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the serpin family.|||First detected at 12.5 dpc in cartilage primordium, it is present in the osseous matrix of developing limbs, vertebrae, ribs and skull. At 16.5 dpc it is detected in bone matrix and smooth muscle, and at lower levels in connective tissue, bronchial epithelial cells, metanephron microtubules, and skin.|||Highly expressed in the liver, gastric glandular mucosa and renal tubules. It is also expressed in the brain, heart, lung retina and testes.|||Interacts with PNPLA2; this interaction stimulates the phospholipase A2 activity of PNPLA2.|||Melanosome|||Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity.|||Secreted http://togogenome.org/gene/10090:Pamr1 ^@ http://purl.uniprot.org/uniprot/Q8BU25 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Although related to peptidase S1 family, lacks the conserved active Ser residue in position 665 which is replaced by a Thr, suggesting that it has no protease activity.|||Belongs to the peptidase S1 family.|||Down-regulated in dystrophin-mutant mdx muscle cell line.|||May play a role in regeneration of skeletal muscle.|||Predominantly expressed in normal skeletal muscle and brain. Expression is enhanced in the regenerating area of injured skeletal muscle in mice.|||Secreted http://togogenome.org/gene/10090:Rdh5 ^@ http://purl.uniprot.org/uniprot/O55240 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed during embryonic development, especially in the developing central nervous system and sensory organs, cranial and spinal ganglia and endoderm of foregut and hindgut. At 10 dpc, detected along the entire neural tube, the mid- and hindbrain floor, the central canal of the brain vesicles, spinal cord, lung mesenchyme, the trabecular layer of the heart ventricles, endoderm and endodermally-derived structures such as tracheal epithelium and liver. At 11 dpc, expressed in the brain vesicles, along the spinal cord, myotome, migrating muscle progenitor cells in the body wall, cells of the genital ridge, spinal ganglion, liver, cerebellar primordium, basal cells of the neuroepithelium of the mesenchephalic flexure, collections of cells in the pons, Rathke's pouch, spinal and cranial ganglia and the floor plate, retina, lens, optic stalks and the neural crest-derived mesenchyme in the anterior eye segment. During eye development, expression restricted to the retinal pigment epithelium of the posterior hemisphere at 18 dpc, with expression levels increasing postnatally to P16.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the oxidation of cis-isomers of retinol, including 11-cis-, 9-cis-, and 13-cis-retinol in an NAD-dependent manner (PubMed:10588954, PubMed:9539749). Has no activity towards all-trans retinal (By similarity). Plays a significant role in 11-cis retinol oxidation in the retinal pigment epithelium cells (RPE). Also recognizes steroids (androsterone, androstanediol) as its substrates (By similarity).|||Endoplasmic reticulum membrane|||Expressed in eye, liver, kidney, brain, intestine, placenta, epididymus and submaxillary gland. In eye, strongly expressed in the retinal pigment epithelium, with lower expression levels detected in the inner segment of the photoreceptor cells and in the outer plexiform layer. In kidney, strong expression detected in the distal tubules and the transitional epithelium in the renal pelvis, with weaker expression detected in the epithelium of the outer stripe of the outer zone of the medulla. In liver, detected in hepatocytes in the centrilobular area. In lung, present in club cells in the epithelium of the bronchiole, in parenchyma and in cartilage surrounding the secondary bronchi. In skin, expressed in epidermis, hair follicles and mast cells in the dermis. Expressed in heart (PubMed:10588954, PubMed:10739682). Not detected in heart (PubMed:9539749). Not detected in lung, spleen, skeletal muscle and testis.|||Homodimer.|||Inhibited by 9-cis-, 13-cis- and all-trans-retinoic acids, with the most potent inhibitor being 13-cis-retinoic acid. Weakly inhibited by oleic acid.|||Mutant mice develop normally and are fertile. No abnormalities can be found in the retinal structure, rhodopsin content and fundus appearance of their eyes. Mice display a mild visual phenotype of impaired dark adaptation and accumulation of 11-cis- and 13-cis-retinols and 11-cis- and 13-cis-retinyl esters in the eyes.|||The last 8 amino acids of the C-terminal tail are important for a proper localization as well as for the in vivo enzymatic activity. http://togogenome.org/gene/10090:Mex3c ^@ http://purl.uniprot.org/uniprot/Q05A36 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds RNA through its KH domains.|||Cytoplasm|||Interacts with USP7, which antagonizes the ability to degrade mRNA.|||Nucleus|||Phosphorylated.|||RNA-binding protein. May be involved in post-transcriptional regulatory mechanisms, modulating levels of some mRNAs by promoting their degradation in a way involving ubiquitin ligase activity. May act as suppressor of replication stress and chromosome missegregation. http://togogenome.org/gene/10090:Myo1g ^@ http://purl.uniprot.org/uniprot/Q5SUA5 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cell membrane|||Interacts with calmodulin; via its IQ motifs.|||It is uncertain whether Met-1 or Met-7 is the initiator.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).|||Specifically expressed in hematopoietic cells. Detected in adult tissues of the immune system such as thymus, lymph nodes and spleen, but not in brain, lung, heart, liver, small intestine, testis and kidney (at protein level). Highly expressed in T-lymphocytes; constitutes the most highly expressed class I myosin in naive CD4 and CD8 T-cells. Also present in B-lymphocytes.|||T-cells display impaired migration patterns and are less efficient in scanning and evaluating antigen-presenting cells. T-cells show global reduction in membrane tension, while their homeostatic tissue distribution and responsiveness to T-cell receptor (TCR) engagement are unaffected. However, T-cells move faster and straighter, leading to defects in detection of antigen-presenting cells, specifically for detection of rare antigens.|||The myosin tail domain mediates binding to phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) and binds to membranous compartments. It is required for recruitment to Fc-gamma receptor (Fc-gamma-R) phagocytic cups.|||Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration (PubMed:25083865). Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication (PubMed:25083865). Also required in B-cells, where it regulates different membrane/cytoskeleton-dependent processes (PubMed:24310084). Involved in Fc-gamma receptor (Fc-gamma-R) phagocytosis (PubMed:23038771).|||phagocytic cup http://togogenome.org/gene/10090:Nin ^@ http://purl.uniprot.org/uniprot/Q61043 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated with the centrosome throughout the cell cycle (PubMed:8834802). During mitosis, it is associated with the centrosome and the mitotic spindle (PubMed:8834802). At anaphase, it is only localized to centrosomes (PubMed:8834802). Isoform 4 is highly expressed in postmitotic cortical neurons during neurogenesis (PubMed:27565344).|||Centrosomal protein required for the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15784680, PubMed:10934040). May also act as a centrosome maturation factor (By similarity). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15784680). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (By similarity). Required for centriole organization and microtubule anchoring at the mother centriole (By similarity).|||Cytoplasm|||Homooligomer (By similarity). Interacts with GSK3B/GSK3-beta via its C-terminal domain (By similarity). Interacts with C14ORF166, such interaction may prevent its phosphorylation by GSK3B (By similarity). Interacts with AUNIP (via N-terminus) (By similarity). Identified in a complex with AUNIP and AURKA (By similarity). Interacts with CCDC120 (By similarity). Interacts (via C-terminus) with CEP250 (PubMed:27565344). Interacts with CEP170 (PubMed:27565344). Interacts (via N-terminus) with the gamma-tubulin ring complex component TUBGCP3 (PubMed:15784680). Interacts with gamma-tubulin (PubMed:15784680). Isoform 4 does not interact with CEP170 or CEP250 (PubMed:27565344).|||Phosphorylated by AURKA/Aurora kinase A and PKA kinases but not CK2 or AURKB/Aurora kinase B.|||The N-terminal domain is important for targeting to the mother centriole, although it is not sufficient by itself for centrosomal localization.|||There is conflicting information regarding the regions required for centrosomal localization (PubMed:15784680). One study shows that the region 1591-1671 is necessary and sufficient for targeting to the centrosome (By similarity). Another study shows that a separate region within the coiled-coil domain, 1279-1565, is important for centrosomal localization (By similarity). However, a third study shows that the coiled-coil region (373-1874) is not sufficient for centrosomal localization and instead localizes to cytoplasmic speckles (PubMed:15784680). The observed differences might be due to oligomerization of the longer coiled-coil domain-containing sequence, which would mask the shorter centrosomal targeting sequences (PubMed:15784680).|||Widely expressed. Highly expressed in spleen, bone marrow and skin. Weakly expressed in liver and small intestine. Expressed in brain.|||centriole|||centrosome http://togogenome.org/gene/10090:Abcd1 ^@ http://purl.uniprot.org/uniprot/P48410 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen. Has fatty acyl-CoA thioesterase (ACOT) and ATPase activities. Coupled to the ATP-dependent transporter activity has also a fatty acyl-CoA thioesterase activity (ACOT) and hydrolyzes VLCFA-CoA into VLCFA prior their ATP-dependent transport into peroxisomes, the ACOT activity is essential during this transport process (By similarity). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:9126326, PubMed:9418970, PubMed:9256488, PubMed:18854420, PubMed:23123468, PubMed:23604518, PubMed:25255441, PubMed:25583114, PubMed:26108493). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance (PubMed:11875044, PubMed:15489218, PubMed:26108493). Controls also the cellular response to oxidative stress by regulating mitochondrial functions such as mitochondrial oxidative phosphorylation and depolarization (PubMed:18344354, PubMed:22521832, PubMed:23604518, PubMed:25583114). And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (PubMed:18723473).|||Abcd1 hemizygous males are viable and apparently healthy and they show no detectable motor defect for at least 4-month-old. Inbreeding homozygous and hemizygous Abcd1-deficient mice show a reduction of fertility. Moreover, among several 6-month-old mice, there is at least one apparently infertile mutant of each sex. The infertile hemizygous male show additionally a severe testicular atrophy (PubMed:9418970). Abcd1 hemizygous mutant male and homozygous mutant mice grow normally, are fer- tile, and appear normal at least up to one year of age (PubMed:9126326). Abcd1 hemizygous mutant male and homozygous mutant mice grow normally, are fer- tile, and appear normal at least up to 6 months of age (PubMed:9256488). At 20 months of age, Abcd1 homozygous mice present an impairment of their locomotor coordination and exploratory abilities (PubMed:11875044, PubMed:15489218). Double Abcd1 and Abcd2 knockout mice exhibit severe impairment of their locomotor coordination and exploratory abilities already at 15 months of age (PubMed:15489218).|||Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.|||By dietary fenofibrate.|||Can form homodimers and heterodimers with ABCD2 and ABCD3 (PubMed:15276650). Dimerization is necessary to form an active transporter (By similarity). The minimal functional unit is a homodimer but the major oligomeric form in peroxisomal membrane is a homotetramer. Forms heterotramers with ABCD2 (By similarity). Interacts with PEX19; facilitates ABCD1 insertion into the peroxisome membrane (By similarity).|||Endoplasmic reticulum membrane|||Lysosome membrane|||Mitochondrion membrane|||Most abundant in embryo. Gradually decreases during maturation.|||Peroxisome membrane|||The NH2-terminal transmembrane domaine (TMD) is involved in the recognition of substrates, and undergoes a conformational change upon ATP binding to the COOH-terminal nucleotide binding domain (NBD).|||Tyrosine-phosphorylated.|||Widely expressed at low levels with higher levels in heart, lung, intestine and spleen than in skeletal muscle, brain, liver and kidney. http://togogenome.org/gene/10090:Selenbp2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J135|||http://purl.uniprot.org/uniprot/Q63836 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the selenium-binding protein family.|||Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria. Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport.|||Interacts with USP33.|||Mainly expressed in liver.|||Membrane|||Nucleus|||Selenium- and acetaminophen-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity).|||The N-terminus is blocked.|||cytosol http://togogenome.org/gene/10090:Obp1a ^@ http://purl.uniprot.org/uniprot/Q9D3H2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Binds the chemical odorant 2-isobutyl-3-methoxypyrazine.|||Expressed in nasal mucosa (at protein level) (PubMed:8529023). Specifically detected in septal and lateral nasal glands (PubMed:9661663).|||May form a heterodimer with OBP1B.|||Secreted|||The N-terminus may be blocked. http://togogenome.org/gene/10090:Iqgap2 ^@ http://purl.uniprot.org/uniprot/Q3UQ44 ^@ Function ^@ Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin. http://togogenome.org/gene/10090:Vnn3 ^@ http://purl.uniprot.org/uniprot/Q9QZ25 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.|||Cell membrane|||Ubiquitous with higher expression in liver. http://togogenome.org/gene/10090:C1qtnf2 ^@ http://purl.uniprot.org/uniprot/Q9D8U4 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Involved in the regulation of lipid metabolism in adipose tissue and liver.|||It is uncertain whether Met-1 or Met-10 is the initiator.|||Knockout mice are born at the expected Mendelian ratio and appear normal with no gross developmental abnormalities. A reduction of body weight is observed in male, but not female, due to increased metabolic rate and energy expenditure. CTRP2 deficiency up-regulates the expression of lipolytic enzymes and protein kinase A signaling, resulting in enhanced adipose tissue lipolysis. Knockout mice also have altered hepatic and plasma lipid profiles. In contrast to lipid metabolism, whole-body glucose metabolism is not affected.|||May interact with ERFE.|||Secreted http://togogenome.org/gene/10090:Or7g12 ^@ http://purl.uniprot.org/uniprot/Q7TRG8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Csk ^@ http://purl.uniprot.org/uniprot/P41241 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.|||Cell membrane|||Cytoplasm|||Homodimer (via SH3-domain) (By similarity). Interacts with PTPN22 (PubMed:8890164). Interacts with phosphorylated SIT1, PAG1, LIME1 and TGFB1I1; these interactions serve to recruit CSK to the membrane where it can phosphorylate and inhibit Src-family kinases (PubMed:9858471, PubMed:12218089, PubMed:12612075, PubMed:16166631). Interacts with SRCIN1 (By similarity). Interacts with RHOH (By similarity). Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-96' (PubMed:28290451). Interacts (via SH2 domain) with PRAG1 (when phosphorylated at 'Tyr-391'); this interaction prevents translocation of CSK from the cytoplasm to the membrane leading to increased activity of CSK (By similarity). Interacts with LRRK1 (PubMed:23526378).|||Mice die between day 9 and day 10 of gestation with several defects including a non-functional neural tube. SRC and FYN kinases show increased activity when CSK is missing.|||Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK (By similarity).|||Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated (By similarity).|||The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain.|||Ubiquitous, but most abundant in thymus and spleen, as well as in neonatal brain. http://togogenome.org/gene/10090:Pdgfrl ^@ http://purl.uniprot.org/uniprot/A0A0R4J0C9|||http://purl.uniprot.org/uniprot/Q6PE55 ^@ Subcellular Location Annotation|||Subunit ^@ Forms a complex composed of PDGFRL, TNK2 and GRB2.|||Secreted http://togogenome.org/gene/10090:Awat1 ^@ http://purl.uniprot.org/uniprot/A2ADU9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters (By similarity). Shows a strong preference for decyl alcohol (C10), with less activity towards C16 and C18 alcohols (By similarity). Shows a strong preference for saturated acyl-CoAs (By similarity).|||Belongs to the diacylglycerol acyltransferase family.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Pate4 ^@ http://purl.uniprot.org/uniprot/Q09098 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PATE family.|||By castration in the ventral lobe of prostate. This induction is suppressed by subsequent dihydroxytestosterone administration.|||Enhances sperm motility. Binds to calmodulin and inhibits calcium transport into spermatozoa. May modulate the function of nicotinic acetylcholine receptors.|||Expressed in prostate, testis, eye, kidney and skeletal muscle. Expressed in the dorsal lobe of prostate. Not expressed in the ventral lobe of prostate.|||Secreted http://togogenome.org/gene/10090:Slc22a20 ^@ http://purl.uniprot.org/uniprot/Q80UJ1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Expressed at embryonic day 7, but not later in embryogenesis. Expressed in adult.|||Highly expressed in olfactory mucosa. Weakly expressed in testis. Not detected in heart, spleen, lung, kidney or brain.|||Membrane|||Organic anion transporter that mediates the uptake of estrone sulfate. Inhibited by probenecid, propionate, 2-methylbutyrate, 3-methylbutyrate, benzoate, heptanoate and 2-ethylhaxanoate. May act as an odorant transporter. http://togogenome.org/gene/10090:Idnk ^@ http://purl.uniprot.org/uniprot/D3Z4J6|||http://purl.uniprot.org/uniprot/Q8R0J8 ^@ Similarity ^@ Belongs to the gluconokinase GntK/GntV family. http://togogenome.org/gene/10090:Afg3l1 ^@ http://purl.uniprot.org/uniprot/Q920A7 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Homooligomer (PubMed:17101804). Forms heterooligomers with SPG7 and AFG3L2 (PubMed:17101804, PubMed:19656850). Interacts with SPG7 and AFG3L2 (PubMed:19656850).|||In the C-terminal section; belongs to the peptidase M41 family.|||In the N-terminal section; belongs to the AAA ATPase family.|||Mitochondrion inner membrane|||Putative ATP-dependent protease. Required for the maturation of paraplegin (SPG7) after its cleavage by mitochondrial-processing peptidase (MPP), converting it into a proteolytically active mature form.|||The orthologous human gene is a pseudogene. http://togogenome.org/gene/10090:Cfap91 ^@ http://purl.uniprot.org/uniprot/Q8BRC6 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CFAP91 family.|||Cytoplasm|||Expressed in the testis, in cells involved in spermatogenesis.|||Expression begins in 1 week old mice.|||Involved in sperm flagellum axonemal organization and function (By similarity). May regulate cilium motility through its role in the assembly of the axonemal radial spokes (By similarity).|||Mitochondrion|||Part of a complex containing MYCBP, AKAP1 and PRKAR2B.|||Phosphorylated by PKA.|||cilium axoneme http://togogenome.org/gene/10090:Adora2b ^@ http://purl.uniprot.org/uniprot/Q60614 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. http://togogenome.org/gene/10090:Xpc ^@ http://purl.uniprot.org/uniprot/P51612 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the XPC family.|||Chromosome|||Component of the XPC complex composed of XPC, RAD23B and CETN2. Interacts with RAD23A; the interaction is suggesting the existence of a functional equivalent variant XPC complex. Interacts with TDG; the interaction is demonstrated using the XPC:RAD23B dimer. Interacts with SMUG1; the interaction is demonstrated using the XPC:RAD23B dimer. Interacts with DDB2. Interacts with CCNH, GTF2H1 and ERCC3. Interacts with E2F1 and KAT2A; leading to KAT2A recruitment to promoters and subsequent acetylation of histones.|||Cytoplasm|||In absence of DNA repair, the XPC complex also acts as a transcription coactivator: XPC interacts with the DNA-binding transcription factor E2F1 at a subset of promoters to recruit KAT2A and histone acetyltransferase complexes (HAT). KAT2A recruitment specifically promotes acetylation of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby promoting expression of target genes.|||Involved in global genome nucleotide excision repair (GG-NER) by acting as damage sensing and DNA-binding factor component of the XPC complex. Has only a low DNA repair activity by itself which is stimulated by RAD23B and RAD23A. Has a preference to bind DNA containing a short single-stranded segment but not to damaged oligonucleotides. This feature is proposed to be related to a dynamic sensor function: XPC can rapidly screen duplex DNA for non-hydrogen-bonded bases by forming a transient nucleoprotein intermediate complex which matures into a stable recognition complex through an intrinsic single-stranded DNA-binding activity. The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. XPC:RAD23B contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA glycosylases TDG and SMUG1.|||Nucleus|||Sumoylated; sumoylation promotes ubiquitination by RNF111.|||Ubiquitinated upon UV irradiation; the ubiquitination requires the UV-DDB complex, appears to be reversible and does not serve as a signal for degradation. Ubiquitinated by RNF11 via 'Lys-63'-linked ubiquitination. Ubiquitination by RNF111 is polysumoylation-dependent and promotes nucleotide excision repair. http://togogenome.org/gene/10090:Cd151 ^@ http://purl.uniprot.org/uniprot/O35566 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Essential for the proper assembly of the glomerular and tubular basement membranes in kidney.|||Interacts with integrins ITGA3:ITGB1, ITGA5:ITGB1, ITGA3:ITGB1 and ITGA6:ITGB4 and with CD9 and CD181. Interacts (via the second extracellular domain) with integrin ITGAV:ITGB3.|||Membrane|||Palmitoylated. Palmitoylation by ZDHHC2 regulates CD151 expression, association with other tetraspanin family proteins and function in cell adhesion. http://togogenome.org/gene/10090:Sec63 ^@ http://purl.uniprot.org/uniprot/Q8VHE0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Expressed in kidney (at protein level).|||Knockout mice exhibit very early embryonic lethality before E7.5. Conditional ubiquitous or kidney-specific knockdown results in polycystic liver and kidney phenotypes, respectively.|||Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER) (PubMed:22375059). Proposed to play an auxiliary role in recognition of precursors with short and apolar signal peptides. May cooperate with SEC62 and HSPA5/BiP to facilitate targeting of small presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen (By similarity). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (PubMed:21685914).|||The ER translocon complex consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63. http://togogenome.org/gene/10090:Olig1 ^@ http://purl.uniprot.org/uniprot/Q9JKN5 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By SHH.|||Expressed in the ventral spinal cord as early as 9.5 dpc. Expression declines to undetectable levels by 10.5 dpc and reappears in a narrow zone within the ventral neuroepithelium of the spinal cord. In the 14.5 dpc spinal cord, expressed in the oligodendrocyte progenitors of the ventral ventricular zone, but not dorsal root ganglia Schwann cells. Also expressed scattered in the mantle zone, likely corresponding to oligodendrocyte progenitors migrating out from their site of origin. By 15.5 dpc, dispersed throughout the gray matter, with little or no residual expression in the ventricular zone. In the postnatal brain, present preferentially in the white matter, such as corpus callosum and cerebellar medulla. Expressed in the olfactory epithelium from 11.5dpc onward.|||Expressed specifically in brain.|||Nucleus|||Promotes formation and maturation of oligodendrocytes, especially within the brain. Cooperates with OLIG2 to establish the pMN domain of the embryonic neural tube. http://togogenome.org/gene/10090:Vpreb1b ^@ http://purl.uniprot.org/uniprot/P13373 ^@ Function|||Similarity|||Tissue Specificity ^@ Associates with the Ig-mu chain to form a molecular complex that is expressed on the surface of pre-B-cells. This complex presumably regulates Ig gene rearrangements in the early steps of B-cell differentiation.|||Belongs to the immunoglobulin superfamily.|||Only expressed by pre-B-cells. http://togogenome.org/gene/10090:Pcdh18 ^@ http://purl.uniprot.org/uniprot/Q8VHR0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed at high levels throughout the developing embryo, except in the heart and liver. In the developing brain, expressed at high levels in the ventricular zone (vz) in the forebrain and midbrain. Expression in the developing brain is maximal around birth and gradually decreases until it is completely absent from the adult brain.|||Interacts with DAB1.|||Potential calcium-dependent cell-adhesion protein.|||Predominantly expressed in kidney and lung. http://togogenome.org/gene/10090:Pde12 ^@ http://purl.uniprot.org/uniprot/Q3TIU4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CCR4/nocturin family.|||Enzyme that cleaves 2',5'-phosphodiester bond linking adenosines of the 5'-triphosphorylated oligoadenylates, triphosphorylated oligoadenylates referred as 2-5A modulates the 2-5A system. Degrades triphosphorylated 2-5A to produce AMP and ATP. Also cleaves 3',5'-phosphodiester bond of oligoadenylates. Plays a role as a negative regulator of the 2-5A system that is one of the major pathways for antiviral and antitumor functions induced by interferons (IFNs). Suppression of this enzyme increases cellular 2-5A levels and decreases viral replication in cultured small-airway epithelial cells.|||Mitochondrion matrix http://togogenome.org/gene/10090:Acp2 ^@ http://purl.uniprot.org/uniprot/P24638 ^@ PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the histidine acid phosphatase family.|||Lysosome lumen|||Lysosome membrane|||The membrane-bound form is converted to the soluble form by sequential proteolytic processing. First, the C-terminal cytoplasmic tail is removed. Cleavage by a lysosomal protease releases the soluble form in the lysosome lumen (By similarity). http://togogenome.org/gene/10090:Zfand5 ^@ http://purl.uniprot.org/uniprot/O88878 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain, muscle, eye, and heart, lower expression in lung, kidney, and spleen, and very low expression in liver. Expressed in myoblast C2C12 cells (at protein level).|||Homooligomer and/or heterooligomer. Interacts (via A20-type domain) with IKBKG and RIPK1 and with TRAF6 (via AN1-type domain) (By similarity). Interacts with ubiquitin and polyubiquitinated proteins. Identified in a heterotrimeric complex with ubiquitin and SQSTM1, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (By similarity).|||Involved in protein degradation via the ubiquitin-proteasome system. May act by anchoring ubiquitinated proteins to the proteasome. Plays a role in ubiquitin-mediated protein degradation during muscle atrophy. Plays a role in the regulation of NF-kappa-B activation and apoptosis. Inhibits NF-kappa-B activation triggered by overexpression of RIPK1 and TRAF6 but not of RELA. Inhibits also tumor necrosis factor (TNF), IL-1 and TLR4-induced NF-kappa-B activation in a dose-dependent manner. Overexpression sensitizes cells to TNF-induced apoptosis. Is a potent inhibitory factor for osteoclast differentiation.|||Resistance to muscle atrophy accompanied by abnormal accumulation of polyubiquitinated proteins in skeletal muscle.|||The A20-type zinc finger directly binds polyubiquitin chains and associates with the 26S proteasome. The zinc-finger A20-type domain is essential for inhibition of NF-kappa-B activation.|||Up-regulated after TNFSF11 stimulation. Expression also induced by other cytokines such as TNF and IL1B. No significant inhibitory effect on the NF-kappa-B pathway is observed. Expression is increased in both denervation- and fasting-induced muscle atrophy. http://togogenome.org/gene/10090:Ccar1 ^@ http://purl.uniprot.org/uniprot/Q8CH18 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation. May be involved in apoptosis signaling in the presence of the retinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation (By similarity). In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells (PubMed:23887938).|||Contaminating sequence. Potential poly-A sequence.|||Directly interacts with ESR1, NR3C1 and p53/TP53. Interacts (via N-terminus) with CALCOCO1. Interacts with MED1 and GATA1. Interacts with AR and GATA2 (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Ppm1a ^@ http://purl.uniprot.org/uniprot/P49443|||http://purl.uniprot.org/uniprot/Q9EQE3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling (By similarity). Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.|||Membrane|||Monomer (By similarity). Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling (By similarity). Interacts with the phosphorylated form of IKBKB/IKKB (By similarity).|||N-myristoylation is essential for the recognition of its substrates for dephosphorylation.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Mpdu1 ^@ http://purl.uniprot.org/uniprot/Q8R0J2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MPDU1 (TC 2.A.43.3) family.|||Membrane|||Required for normal utilization of mannose-dolichol phosphate (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors. http://togogenome.org/gene/10090:Tmem33 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Z3|||http://purl.uniprot.org/uniprot/Q9CR67|||http://purl.uniprot.org/uniprot/Q9CZM3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a regulator of the tubular endoplasmic reticulum (ER) network by modulating intracellular calcium homeostasis. Mechanistically, stimulates PKD2 calcium-dependent activity (PubMed:31048699). Suppresses the RTN3/4-induced formation of the ER tubules. Positively regulates PERK-mediated and IRE1-mediated unfolded protein response signaling. Plays an essential role in VEGF-mediated release of Ca(2+) from ER stores during angiogenesis. Also plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26. Participates in lipid metabolism by acting as a downstream effector of the pyruvate kinase/PKM. Forms a complex with RNF5 to facilitate polyubiquitination and subsequent degradation of SCAP on the ER membrane (By similarity).|||Belongs to the PER33/POM33 family.|||Deletion mice show renal protection against acute kidney injury (AKI).|||Endoplasmic reticulum membrane|||Interacts with EIF2AK3 (By similarity). Interacts with RTN1, RTN2, RTN3, RTN4 and ARL6IP1 (By similarity). Interacts with RNF5. Interacts with RNF26 (By similarity). Interacts with PKD2 (PubMed:31048699).|||Melanosome|||Membrane|||Nucleus envelope http://togogenome.org/gene/10090:Sult2a4 ^@ http://purl.uniprot.org/uniprot/D3Z6M7 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Ahr ^@ http://purl.uniprot.org/uniprot/P30561|||http://purl.uniprot.org/uniprot/Q3U5D9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AHR knockdown in the retina results in reduced electroretinogram responses, thinning of the outer segment, and degeneration of photoreceptors.|||Although it interacts with NEDD8, it does not seem to be neddylated.|||Between 10 dpc and 12 dpc, abundantly expressed in neuroepithelium, branchial arches, cranial nerves, liver, heart and spinal ganglia.|||Cytoplasm|||Expressed in all tissues tested including brain, heart, kidney, liver, lung, muscle, ovary, skin, spleen and thymus.|||Homodimer (PubMed:24001774). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (By similarity). Interacts with ARNT; the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:24001774, PubMed:28396409). Binds MYBBP1A (PubMed:11956195). Interacts with coactivators including SRC-1, RIP140 and NOCA7, and with the corepressor SMRT. Interacts with NEDD8 and IVNS1ABP (PubMed:12215427). Interacts with BMAL1 (PubMed:20106950). Interacts with HSP90AB1 (PubMed:15581363). Interacts with TIPARP; leading to mono-ADP-ribosylation of AHR and subsequent inhibition of AHR (By similarity).|||Induced or repressed by TGF-beta and dioxin in a cell-type specific fashion. Repressed by cAMP, retinoic acid, and TPA.|||Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:10639156, PubMed:10973493, PubMed:1314586, PubMed:7961644, PubMed:7969080, PubMed:8806883, PubMed:9427285, PubMed:33436590). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (By similarity). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:20106950, PubMed:28396409). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:10639156, PubMed:10973493, PubMed:1314586, PubMed:7961644, PubMed:7969080, PubMed:8806883, PubMed:9427285). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (By similarity). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (By similarity). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (By similarity). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (By similarity). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (By similarity). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:20106950). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28396409).|||Mono-ADP-ribosylated, leading to inhibit transcription activator activity of AHR.|||Nucleus|||The PAS 1 domain is essential for dimerization and also required for AHR:ARNT heterodimerization.|||There are four common alleles; AHRB1; AHRB2; AHRB3 and AHRD. The sequence of AHRB2 is shown here. http://togogenome.org/gene/10090:Fgfr1 ^@ http://purl.uniprot.org/uniprot/P16092|||http://purl.uniprot.org/uniprot/Q8CIM9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Embryonic lethality around gastrulation, due to growth defects during early embryonic development and aberrant mesoderm patterning.|||Membrane|||Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:10821861, PubMed:1309590, PubMed:17086194). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23. Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains). Interacts with FRS2. Interacts with RPS6KA1. Interacts (via C-terminus) with NEDD4 (via WW3 domain). Interacts with KL (PubMed:17086194). Interacts with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10 (By similarity). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (By similarity). Interacts with SOX2 and SOX3 (PubMed:17728342). Interacts with FLRT1, FLRT2 and FLRT3 (PubMed:16872596). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (By similarity).|||N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.|||Nucleus|||Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues (By similarity).|||Proposes two coding sequences for the same mRNA.|||The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains (By similarity).|||Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation (By similarity).|||Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1 (By similarity).|||Vesicle|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Prorsd1 ^@ http://purl.uniprot.org/uniprot/Q9D820 ^@ Similarity ^@ Belongs to the PRORSD1 family. http://togogenome.org/gene/10090:Ergic1 ^@ http://purl.uniprot.org/uniprot/Q4FK22|||http://purl.uniprot.org/uniprot/Q9DC16 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ERGIC family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||May form a heteromeric complex composed of ERGIC1, ERGIC2 and ERGIC3 (By similarity). Within the complex, the interaction with ERGIC3 is direct (By similarity). Interacts with ERGIC3/ERV46 (By similarity).|||N-glycosylated.|||Plays a role in transport between endoplasmic reticulum and Golgi.|||Possible role in transport between endoplasmic reticulum and Golgi. http://togogenome.org/gene/10090:Fndc3a ^@ http://purl.uniprot.org/uniprot/Q8BX90 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FNDC3 family.|||Golgi apparatus membrane|||Mediates spermatid-Sertoli adhesion during spermatogenesis.|||Testis. Localizes to the acrosome of spermatids, as well as to Leydig cells. Can be detected on the acrosome beginning at steps 2-3 and continuing until step 12 of spermiogenesis. http://togogenome.org/gene/10090:Or9k2 ^@ http://purl.uniprot.org/uniprot/Q8VFU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or10ag2 ^@ http://purl.uniprot.org/uniprot/A2AT85 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ear2 ^@ http://purl.uniprot.org/uniprot/P97425|||http://purl.uniprot.org/uniprot/W0UVF7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pancreatic ribonuclease family.|||Cytoplasmic granule|||Cytotoxin and helminthotoxin with ribonuclease activity. Selectively chemotactic for dendritic cells. Possesses a wide variety of biological activities.|||The N-terminal region is necessary for mediating chemotactic activity. http://togogenome.org/gene/10090:Prrg3 ^@ http://purl.uniprot.org/uniprot/Q6PAQ9 ^@ PTM|||Subcellular Location Annotation ^@ Gla residues are produced after subsequent post-translational modifications of glutamate by a vitamin K-dependent gamma-carboxylase.|||Membrane http://togogenome.org/gene/10090:Krtap9-3 ^@ http://purl.uniprot.org/uniprot/Q3V2C1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 9 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).|||Interacts with hair keratins. http://togogenome.org/gene/10090:Cxxc1 ^@ http://purl.uniprot.org/uniprot/Q541B1|||http://purl.uniprot.org/uniprot/Q9CWW7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Interacts with SETD1A (By similarity). Interacts with ZNF335 (By similarity). Interacts with PRDM9; this interaction does not link PRDM9-activated recombination hotspot sites with DSB machinery and is not required for the hotspot recognition pathway (PubMed:27932493, PubMed:30365547). Interacts with histone H3K4me3 (PubMed:30365547).|||Cxxc1 knockout male mice are fertile. In contrast Cxxc1 germ cell-specific knockout female mice are sterile.|||Expressed in seminiferous tubules and in both germ cells and Sertoli cells. Highly expressed in spermatogonia, weakly expressed in leptonema and zygonema, and then again high expression in pachynema and diplonema, decreasing to undetectable levels in spermatids.|||Nucleus|||Nucleus speckle|||Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG. http://togogenome.org/gene/10090:Defa41 ^@ http://purl.uniprot.org/uniprot/D3YX02 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Senp8 ^@ http://purl.uniprot.org/uniprot/A0A1L1SRH8|||http://purl.uniprot.org/uniprot/Q3UWN3|||http://purl.uniprot.org/uniprot/Q9D2Z4 ^@ Function|||Similarity ^@ Belongs to the peptidase C48 family.|||Protease that catalyzes two essential functions in the NEDD8 pathway: processing of full-length NEDD8 to its mature form and deconjugation of NEDD8 from targeted proteins such as cullins or p53. http://togogenome.org/gene/10090:R3hdml ^@ http://purl.uniprot.org/uniprot/A2A5I3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CRISP family.|||Despite its name, it does not contain a R3H domain.|||Putative serine protease inhibitor.|||Secreted http://togogenome.org/gene/10090:Or1j4 ^@ http://purl.uniprot.org/uniprot/Q8VFP8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Riiad1 ^@ http://purl.uniprot.org/uniprot/Q3KNY5 ^@ Caution|||Sequence Caution|||Tissue Specificity ^@ Abundant in tissues rich in highly ciliated cells, such as testis, trachea and olfactory epithelium.|||It is uncertain whether Met-1 or Met-28 is the initiator.|||Probable cloning artifact. http://togogenome.org/gene/10090:Arhgef40 ^@ http://purl.uniprot.org/uniprot/Q3UPH7 ^@ Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Intron retention.|||May act as a guanine nucleotide exchange factor (GEF).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Probable cloning artifact.|||Ubiquitously expressed but enriched in brain. In brain, it is expressed at higher level in olfactory bulb and cerebellum and peaks perinatally (from 16 dpc to P0.5). http://togogenome.org/gene/10090:Dtx1 ^@ http://purl.uniprot.org/uniprot/Q61010 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Deltex family.|||Cytoplasm|||Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1 via its N-terminal region and EIF3F, the interaction is required for NOTCH1 deubiquitination. Interacts with EP300. Forms a heterodimer with BBAP; the heterodimerization leading to an increase of in vitro ubiquitin ligase activity. Interacts with ITCH.|||In the CNS, it is expressed in the developing neural tube starting from 10.5 dpc in the spinal cord and around 11.5 dpc in the telencephalon. Expressed ubiquitously throughout the spinal cord and telencephalon during neurogenesis. Expressed throughout the developing retina from 12.5 to 15.5 dpc. Expressed in the developing thymus. Not expressed in the somite or presomite during somitogenesis. Expressed slightly later that Dtx2.|||Nucleus|||Predominantly expressed in the brain and testis. Weakly expressed in the thymus, spleen and ovary. Predominantly expressed in regions containing post-mitotic differentiating neurons.|||Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it also acts as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Involved in neurogenesis, lymphogenesis and myogenesis, and may also be involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1. Functions as an ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity.|||Splicing acceptor site not canonical.|||The WWE domains are thought to mediate some protein-protein interaction, and are frequently found in ubiquitin ligases.|||Ubiquitinated; undergoes 'Lys-29'-linked polyubiquitination catalyzed by ITCH. http://togogenome.org/gene/10090:Vwce ^@ http://purl.uniprot.org/uniprot/Q3U515 ^@ Function|||Subcellular Location Annotation ^@ May be a regulatory element in the beta-catenin signaling pathway and a target for chemoprevention of hapatocellular carcinoma.|||Secreted http://togogenome.org/gene/10090:Mfap5 ^@ http://purl.uniprot.org/uniprot/F8WJ99|||http://purl.uniprot.org/uniprot/Q9QZJ6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MFAP family.|||Forms intermolecular disulfide bonds either with other MAGP-2 molecules or with other components of the microfibrils.|||Interacts with TGFB2 (PubMed:23963447). Interacts with BMP2. Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity).|||May play a role in hematopoiesis. In the cardiovascular system, could regulate growth factors or participate in cell signaling in maintaining large vessel integrity (PubMed:23963447). Component of the elastin-associated microfibrils (By similarity).|||Mice appear normal by several measures, are fertile, and have a normal life span, but are neutropenic.|||extracellular matrix http://togogenome.org/gene/10090:Dmrtc1c2 ^@ http://purl.uniprot.org/uniprot/Q14AJ8|||http://purl.uniprot.org/uniprot/Q9D410 ^@ Similarity ^@ Belongs to the DMRT family. http://togogenome.org/gene/10090:Epm2aip1 ^@ http://purl.uniprot.org/uniprot/Q8VEH5 ^@ Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum|||Interacts with EPM2A. http://togogenome.org/gene/10090:Gse1 ^@ http://purl.uniprot.org/uniprot/Q3U3C9 ^@ Subunit ^@ May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. http://togogenome.org/gene/10090:Serpina3b ^@ http://purl.uniprot.org/uniprot/Q05A44|||http://purl.uniprot.org/uniprot/Q8BYY9 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Or5w19 ^@ http://purl.uniprot.org/uniprot/Q7TR34 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc26a10 ^@ http://purl.uniprot.org/uniprot/F8WGV3 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Gm20921 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Lats1 ^@ http://purl.uniprot.org/uniprot/Q8BYR2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated and phosphorylated during M-phase of the cell cycle (By similarity). Phosphorylated by STK3/MST2 at Ser-908 and Thr-1078, which results in its activation (By similarity). Phosphorylation at Ser-463 by NUAK1 and NUAK2 leads to decreased protein level and is required to regulate cellular senescence and cellular ploidy (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Complexes with CDK1 in early mitosis (By similarity). LATS1-associated CDK1 has no mitotic cyclin partner and no apparent kinase activity (By similarity). Binds phosphorylated ZYX, locating this protein to the mitotic spindle and suggesting a role for actin regulatory proteins during mitosis (By similarity). Binds to and colocalizes with LIMK1 at the actomyosin contractile ring during cytokinesis (By similarity). Interacts (via PPxY motif 2) with YAP1 (via WW domains) (By similarity). Interacts with MOB1A and MOB1B. Interacts with LIMD1, WTIP and AJUBA (By similarity). Interacts with ESR1, DCAF1 and DCAF13; probably recruits DCAF1 and DCAF13 to ESR1 to promote ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (By similarity). Interacts with STK3/MST2; this interaction is inhibited in the presence of DLG5 (By similarity). Interacts with SCRIB in the presence of DLG5 (By similarity). Interacts with WWTR1/TAZ (PubMed:21145499).|||Midbody|||Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:21145499). Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1.|||centrosome|||spindle|||spindle pole body http://togogenome.org/gene/10090:Htra1 ^@ http://purl.uniprot.org/uniprot/Q9R118 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1C family.|||Cell membrane|||First detected at 10.5 dpc. At 11.5 dpc, in the developing heart, expressed in the atrioventricular endocardial cushion and the outflow tract (at protein level). At 14.5 dpc, strong expression in the outflow tracts, including valves. In the developing skeleton, expressed at 12.5 dpc in the vertebral column and limbs. At 14.5 dpc, expressed in rudiments of tendons and ligaments along the vertebrae, as well as in mesenchymal cells surrounding precartilage condensations. Not detected in precartilage condensations, nor in chondrocytes, but strongly expressed in ossification centers. At 17.5 dpc, in the hind limb, significant expression persists in tendons and ligaments, but expression in the forming joints is reduced. At this stage, weakly detected in the thin layer of articular surfaces. Postnatally, in long bones, expressed by terminally differentiated hypertrophic chondrocytes that are committed to degeneration and eventually replaced by bone, as well as by osteoblasts at late differentiation stages and by mature osteocytes. In the developing brain, expressed in specific regions of the neuroepithelium in the forebrain and hindbrain adjacent to the forming choroid plexus. From 17.5 dpc till birth, expressed in neurogenic areas including ventricular zones (at protein level). At 12.5 and 14.5 dpc, expressed in Muellerian duct cells and in the surrounding mesenchyme in both male and female gonads. In the lung, detected in the mesenchymal cells. Expressed at 12.5 dpc in abdominal skin, both in epidermis and dermis. Also expressed in the epithelium of developing whiskers at 14.5 dpc. At later stages, localized in the basal layer of epidermis and in the invading epidermal cells that formed the whisker rudiments (at protein level). 9 days after birth, detected in the whisker outer root sheet (at protein level).|||Forms homotrimers. In the presence of substrate, may form higher-order multimers in a PDZ-independent manner (By similarity). Interacts with TGF-beta family members, including BMP4, TGFB1, TGFB2, activin A and GDF5.|||In the brain, mainly expressed in cortical areas both in glial cells and neurons (at protein level). In bones, deposited in the matrix, with higher level in newly formed bone compared to fully calcified bone (at protein level). Also expressed in the tendons (at protein level). In the articular cartilage, detected only in the deepest zone of the joint cartilage. Not detected in the chondrocytes of the growth plate (at protein level). In an experimental arthritis model, at early disease stages, up-regulated in articular chondrocytes in the deep layers of the cartilage (at protein level). As arthritis progresses, chondrocyte expression expands toward the surface.|||Mutants mice exhibit reduced retinal capillary density, as compared to wild type animals, in all 3 retinal layers, nerve fiber layer, as well as inner and outer plexiform layers.|||Secreted|||Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin. HTRA1-generated fibronectin fragments further induce synovial cells to up-regulate MMP1 and MMP3 production. May also degrade proteoglycans, such as aggrecan, decorin and fibromodulin. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. This activity requires the integrity of the catalytic site, but it is unclear whether it leads to the proteolytic degradation of TGF-beta proteins themselves (PubMed:18551132) or not (PubMed:14973287). By acting on TGF-beta signaling, may regulate many physiological processes, including retinal angiogenesis and neuronal survival and maturation during development. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets.|||The IGFBP N-terminal domain mediates interaction with TSC2 substrate.|||cytosol http://togogenome.org/gene/10090:Prmt9 ^@ http://purl.uniprot.org/uniprot/Q3U3W5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA). Specifically mediates the symmetrical dimethylation of SF3B2. Involved in the regulation of alternative splicing of pre-mRNA.|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.|||Cytoplasm|||Found in a complex with PRMT9, SF3B2 and SF3B4. Interacts with SF3B2.|||This protein should not be confused with Fbxo11 (AC Q7TPD1) that was initially erroneously named Prmt9. http://togogenome.org/gene/10090:Or4c58 ^@ http://purl.uniprot.org/uniprot/Q8VGN4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mlec ^@ http://purl.uniprot.org/uniprot/Q6ZQI3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the malectin family.|||Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan. May play a role in the early steps of protein N-glycosylation (By similarity).|||Endoplasmic reticulum membrane|||Interacts with the oligosaccharyltransferase (OST) complex. http://togogenome.org/gene/10090:Gm20937 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Klf2 ^@ http://purl.uniprot.org/uniprot/Q60843 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with WWP1.|||Nucleus|||Predominant expression in the lungs and spleen.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor that binds to the CACCC box in the promoter of target genes such as HBB/beta globin or NOV and activates their transcription. Might be involved in transcriptional regulation by modulating the binding of the RARA nuclear receptor to RARE DNA elements (By similarity).|||Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein. http://togogenome.org/gene/10090:Insig2 ^@ http://purl.uniprot.org/uniprot/A0A087WQP7|||http://purl.uniprot.org/uniprot/Q91WG1 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the INSIG family.|||Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4.|||Endoplasmic reticulum membrane|||Expressed in liver, testis, kidney, spleen, intestine, brain and adrenal gland.|||Interacts with SCAP; interaction is direct and only takes place in the presence of sterols; it prevents interaction between SCAP and the coat protein complex II (COPII). Associates with the SCAP-SREBP complex (composed of SCAP and SREBF1/SREBP1 or SREBF2/SREBP2); association is mediated via its interaction with SCAP and only takes place in the presence of sterols. Interacts with RNF139. Interacts with RNF145.|||Knockout mice with a conditional deletion of Insig1 in the liver and a germline deletion of Insig2 overaccumulate cholesterol and triglycerides in liver: despite this accumulation, levels of nuclear sterol regulatory element-binding proteins (SREBPs) are not reduced (PubMed:16100574). The amount of HMGCR is also elevated, caused by impaired degradation of the enzyme (PubMed:16100574). Knockout mice with a germline deletion of both Insig1 and Insig2 die within one day of birth (PubMed:16100574, PubMed:16955138). After 18.5 days of development, embryos lacking both Insig1 and Insig2 show defects in midline facial development, ranging from cleft palate to complete cleft face: middle and inner ear structures are abnormal, but teeth and skeletons are normal (PubMed:16955138). The livers and heads of embryos lacking both Insig1 and Insig2 overproduce sterols, causing a marked buildup of sterol intermediates (PubMed:16955138).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates feedback control of cholesterol synthesis.|||Membrane|||Oxidized at Cys-215 in differentiated myotubes, preventing ubiquitination at the same site, and resulting in protein stabilization.|||Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12242332, PubMed:12624180, PubMed:16100574). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:16100574). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (By similarity). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (By similarity). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (By similarity). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase RNF139 (By similarity).|||Phosphorylation at Ser-151 by PCK1 reduces binding to oxysterol, disrupting the interaction between INSIG2 and SCAP, thereby promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes.|||Polyubiquitinated by AMFR/gp78 at Cys-215 in some tissues such as adipose tissues, undifferentiated myoblasts and liver, leading to its degradation. In differentiated myotubes, Cys-215 oxidation prevents ubiquitination at the same site, resulting in protein stabilization.|||The KxHxx motif mediates association with the coatomer complex.|||Up-regulated in differentiating preadipocytes. http://togogenome.org/gene/10090:Piga ^@ http://purl.uniprot.org/uniprot/Q64323 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.|||Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis.|||Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP and PIGQ, DPM2. Interacts with PIGC, PIGH, PIGP, PIGQ and DPM2. The latter is not essential for activity. Interacts directly with PIGY; this interaction regulates glycosylphosphatidylinositol-N-acetylglucosaminyltransferase activity. Interacts with PIGQ.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Tgfbrap1 ^@ http://purl.uniprot.org/uniprot/Q3UR70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAP1 family.|||Cytoplasm|||Early endosome|||Embryonic lethal, both before blastula stage or during gastrulation.|||Interacts with TGFBR2 and ACVR2B; in the absence of ligand stimulation. Interacts with TGFBR1, ACVRL1, BMPR1A and ACVR1B; in the absence of ligand stimulation and to a less extent. Interacts with SMAD4; the interaction seems to be mutually exclusive with the interaction of SMAD4 and phosphorylated SMAD2. May interact with ALOX5 (By similarity). Interacts with RAB5C. Interacts with VPS8, VPS11 and VPS16. Component of the putative class C core vacuole/endosome tethering (CORVET) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS8 and TGFBRAP1 (PubMed:25266290).|||Plays a role in the TGF-beta/activin signaling pathway. It associates with inactive heteromeric TGF-beta and activin receptor complexes, mainly through the type II receptor, and is released upon activation of signaling. May recruit SMAD4 to the vicinity of the receptor complex and facilitate its interaction with receptor-regulated Smads, such as SMAD2 (By similarity).|||Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Functions predominantly in APPL1-containing endosomes and in degradative but not recycling trafficking of endocytosed cargo (By similarity). http://togogenome.org/gene/10090:Rgs8 ^@ http://purl.uniprot.org/uniprot/Q8BXT1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with GNAO1 and GNAI3.|||Membrane|||Nucleus|||Perikaryon|||Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Modulates the activity of potassium channels that are activated in response to DRD2 and CHRM2 signaling.|||dendrite http://togogenome.org/gene/10090:Gng7 ^@ http://purl.uniprot.org/uniprot/Q3UGN1|||http://purl.uniprot.org/uniprot/Q61016 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G protein gamma family.|||Brain. Found in the hippocampus, striatum, midbrain and cortex.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||G proteins are composed of 3 units; alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Plays a role in the regulation of adenylyl cyclase signaling in certain regions of the brain. Plays a role in the formation or stabilzation of a G protein heterotrimer (G(olf) subunit alpha-beta-gamma-7) that is required for adenylyl cyclase activity in the striatum.|||Membrane|||Mice display increased startle response but normal prepulse inhibition of the startle response. No effect on survival to weaning, fertility and mortality. http://togogenome.org/gene/10090:Kynu ^@ http://purl.uniprot.org/uniprot/A2ARD6|||http://purl.uniprot.org/uniprot/Q6NSV5|||http://purl.uniprot.org/uniprot/Q9CXF0 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the kynureninase family.|||Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.|||Cytoplasm|||Homodimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||No visible phenotype. Mice were born at the expected Mendelian ratio and are normal. They however show very high levels of L-3-hydroxykynurenine compared to wild-type mice.|||cytosol http://togogenome.org/gene/10090:Macrod2 ^@ http://purl.uniprot.org/uniprot/Q3UYG8 ^@ Activity Regulation|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, expressed in the neural tube and in the dorsal root and cranial ganglia. At 14.5 dpc, expressed in metanephric glomeruli, but not in the medullary region of the kidney, in the epithelium lining the gut, the stomach and the seminiferous tubules, as well as in lung. Expression is maintained in the dorsal root and cranial ganglia. In the cranial region, up-regulated in the epithelial and mesenchymal components of the tooth bud, in the epithelium lining the primitive nasal cavity, the vestibulocochlear and cochlear ducts and in the cranial ganglia. At 16.5 dpc, expression is maintained in kidney and lung. Detected in the papilla of the whisker follicle. In the eye, highly expressed in the cuboid epithelium of the lens and the inner nuclear (neuroblastic) layer of the retina. Expression begins in the brain, in particular the ventricular zone, and in the heart. At 18.5 dpc, expression is maintained in the brain, including the subventricular zone of striatum and olfactory lobe, the cortical plate, the cerebellar primordium and the inferior colliculus of the tectum. At this stage, the expression in the heart is 45 times lower than in the brain. At birth, still detectable in the metanephric glomeruli, but not in the adrenal gland.|||Expressed in the kidney.|||Interacts with ADP-ribosylated PARP1.|||Nucleus|||Removes ADP-ribose from aspartate and glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins.|||Subject to product inhibition by ADP-ribose. http://togogenome.org/gene/10090:Trmt2b ^@ http://purl.uniprot.org/uniprot/Q8BQJ6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.|||Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and 12S rRNA (PubMed:31736397). Catalyzes the methylation of uridine at position 54 (m5U54) in all tRNAs (PubMed:31736397). Specifically methylates the uridine in position 425 of 12S rRNA (m5U425) (PubMed:31736397). Does not affect RNA stability or mitochondrial translation (By similarity).|||Mitochondrion matrix http://togogenome.org/gene/10090:Tas2r140 ^@ http://purl.uniprot.org/uniprot/Q7TQA4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in 15% taste bud cells in circumvallate and foliate papillae but only in 2% in fungiform papillae.|||Membrane|||Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.|||Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5. http://togogenome.org/gene/10090:Or7a42 ^@ http://purl.uniprot.org/uniprot/Q60892 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Vmn1r72 ^@ http://purl.uniprot.org/uniprot/Q8K3N7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnfrsf8 ^@ http://purl.uniprot.org/uniprot/Q60846 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TNFR8 family.|||By concanavalin A and pokeweed mitogen in splenocytes.|||Cell membrane|||Detected in thymus and in activated splenocytes.|||Interacts with TRAF1, TRAF2, TRAF3 and TRAF5.|||Receptor for TNFSF8/CD30L (PubMed:8543792). May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B (By similarity). http://togogenome.org/gene/10090:Cadps2 ^@ http://purl.uniprot.org/uniprot/Q8BYR5 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-binding protein involved in exocytosis of vesicles filled with neurotransmitters and neuropeptides. Probably acts upstream of fusion in the biogenesis or maintenance of mature secretory vesicles. Regulates neurotrophin release from granule cells leading to regulate cell differentiation and survival during cerebellar development. May specifically mediate the Ca(2+)-dependent exocytosis of large dense-core vesicles (DCVs) and other dense-core vesicles.|||Cytoplasmic vesicle membrane|||Expressed at stable level during brain development, with a higher level in embryonic brain.|||Highly expressed in cerebellum. Also expressed in non-neuronal tissues such as lung, spleen, testis, uterus and ovary. Highly expressed in brain. In brain, it is highly expressed in cerebellum, cortex, olfactory bulb, CA1/CA2 regions of the hippocampus, and dentate gyrus, and weakly or not expressed in the CA3 regions of the hippocampus, striatum, thalamus, superior and inferior colliculi, and brain stem. Not present in adult adrenal glands. Isoform 4, but not isoform 3, is highly expressed in postnatal and adult stages of cerebellum.|||Homodimer. Interacts with the dopamine receptor DRD2 (By similarity).|||Synapse|||The PH domain is essential for regulated exocytosis and binds phospholipids. http://togogenome.org/gene/10090:Slc5a11 ^@ http://purl.uniprot.org/uniprot/Q8K0E3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Involved in the sodium-dependent cotransport of myo-inositol (MI) with a Na(+):MI stoichiometry of 2:1. Exclusively responsible for apical MI transport and absorption in intestine. Can also transport D-chiro-inositol (DCI) but not L-fucose (By similarity). Exhibits stereospecific cotransport of both D-glucose and D-xylose (By similarity). May induce apoptosis through the TNF-alpha, PDCD1 pathway (By similarity). May play a role in the regulation of MI concentration in serum, involving reabsorption in at least the proximal tubule of the kidney (By similarity).|||MI transport activity inhibited by D-chiro-inositol (DCI), phlorizin (Pz) and sodium (Na(+)) (By similarity). Insulin increases D-chiro-inositol uptake (By similarity).|||Membrane http://togogenome.org/gene/10090:Pla2g5 ^@ http://purl.uniprot.org/uniprot/P97391|||http://purl.uniprot.org/uniprot/Q6GTW1 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Cell membrane|||Expressed in peritoneal macrophages (at protein level) (PubMed:16407308). Expressed in heart, skeletal muscle and white adipose tissue (PubMed:24910243).|||Mutant mice show increased high-fat diet induced obesity, increased visceral fat depositions and exacerbated INS resistance (PubMed:24910243). In a model of systemic candidiasis, mutant mice are deficient in clearing C. albicans in kidney, liver and spleen, resulting in increased mortality (PubMed:19342668). In K/BxN serum transfer arthritis model, a well-described mouse model of inflammatory arthritis, mutant mice develop severe autoantibody-driven arthritic response characterized by increased leukocytic tissue infiltration, pannus formation and bone and cartilage destruction (PubMed:20432503). In a model of allergic pulmonary inflammation induced by dust mite D. farinae, mutant mice show impaired T helper type 2 immune response associated with markedly decreased granulocyte infiltration in bronchoalveolar fluid and decreased goblet cell metaplasia (PubMed:20817863). In a model of antigen-induced asthma following repetitive A. Alternata inhalation, mutant mice display impaired pulmonary eosinophil infiltration and overall impaired allergen-induced inflammation (PubMed:29346348).|||Recycling endosome|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity), preferentially releasing fatty acyl groups with a low degree of unsaturation such as oleoyl (C18:1) and linoleoyl (C18:2) groups (PubMed:14962950). Hydrolyzes low-density lipoprotein (LDL) phospholipids releasing unsaturated fatty acids that drive macrophage polarization toward an M2 phenotype (PubMed:14962950, PubMed:24910243). May act in an autocrine and paracrine manner. Contributes to lipid remodeling of cellular membranes at different subcellular locations and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of cardiolipin, a major component of the inner membrane of mitochondria and bacterial membranes (By similarity). Promotes phagocytosis of bacteria in macrophages through production of lysophosphatidylethanolamines (By similarity). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing the phospholipids of the bacterial membrane (PubMed:11694541, PubMed:16407308). Promotes phagocytosis and killing of ingested fungi likely through controlling phagosome-lysosome fusion and phagosome maturation (PubMed:19342668). Plays a role in biosynthesis of cysteinyl leukotrienes (CysLTs) in myeloid cells (By similarity). In eosinophils, triggers perinuclear arachidonate release and LTC4 synthesis in a PLA2G4A-independent way (By similarity). In neutrophils, amplifies CysLTs biosynthesis initiated by PLA2G4A (By similarity). Promotes immune complex clearance in macrophages via stimulating synthesis of CysLTs, which act through CYSLTR1 to trigger phagocytosis (PubMed:20432503). May regulate antigen processing in antigen-presenting cells (PubMed:20817863). In pulmonary macrophages regulates IL33 production required for activation of group 2 innate lymphoid cells (PubMed:29346348). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (By similarity).|||This enzyme lacks one of the seven disulfide bonds found in similar PA2 proteins.|||Up-regulated in white adipocytes upon high-fat diet.|||cis-Golgi network|||phagosome|||trans-Golgi network http://togogenome.org/gene/10090:Pkn3 ^@ http://purl.uniprot.org/uniprot/Q3UQS3|||http://purl.uniprot.org/uniprot/Q8K045 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Contributes to invasiveness in malignant prostate cancer.|||Nucleus|||The C1 domain does not bind the diacylglycerol (DAG).|||Two specific sites, Thr-707 (activation loop of the kinase domain) and Thr-849 (turn motif), need to be phosphorylated for its full activation.|||perinuclear region http://togogenome.org/gene/10090:Pex12 ^@ http://purl.uniprot.org/uniprot/Q5SWQ8|||http://purl.uniprot.org/uniprot/Q8VC48 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pex2/pex10/pex12 family.|||Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (By similarity). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX12 also regulates PEX5 recycling by activating the E3 ubiquitin-protein ligase activity of PEX10 (By similarity). When PEX5 recycling is compromised, PEX12 stimulates PEX10-mediated polyubiquitination of PEX5, leading to its subsequent degradation (By similarity).|||Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.|||Component of the PEX2-PEX10-PEX12 retrotranslocation channel, composed of PEX2, PEX10 and PEX12. Interacts with PEX19 via its cytoplasmic domain.|||Membrane|||Peroxisome membrane|||The RING-type zinc-finger is degenerated and only coordinates one zinc ions, preventing E3 ubiquitin-protein ligase activity.|||The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex. http://togogenome.org/gene/10090:Ubash3a ^@ http://purl.uniprot.org/uniprot/Q3V3E1 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Has very nearly lost all enzyme activity. Has very low, but measurable tyrosine phosphatase activity at pH 5.0.|||Homodimer or homooligomer. Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins. Interacts with dynamin (By similarity).|||Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors, EGFR and PDGFRB, on the cell surface. May inhibit dynamin-dependent endocytic pathways by functionally sequestering dynamin via its SH3 domain (By similarity). Exhibits negligigle protein tyrosine phosphatase activity at neutral pH. May act as a dominant-negative regulator of UBASH3B-dependent dephosphorylation.|||Nucleus http://togogenome.org/gene/10090:Aamdc ^@ http://purl.uniprot.org/uniprot/Q8R0P4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AAMDC family.|||Cytoplasm|||May play a role in preadipocyte differentiation and adipogenesis.|||Widely expressed, with high expression in the adipose tissue and skeletal muscle (at protein level). http://togogenome.org/gene/10090:AAdacl4fm3 ^@ http://purl.uniprot.org/uniprot/B1AVU7 ^@ Similarity ^@ Belongs to the 'GDXG' lipolytic enzyme family. http://togogenome.org/gene/10090:Psmd8 ^@ http://purl.uniprot.org/uniprot/Q9CPS5|||http://purl.uniprot.org/uniprot/Q9CX56 ^@ Caution|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the proteasome subunit S14 family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD8, a base containing 6 ATPases and few additional components. Interacts with DDI2 (By similarity). Interacts with TASOR (PubMed:31112734).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.|||Expressed in the Sertoli cells of the testis.|||It is uncertain whether Met-1 or Met-65 is the initiator. http://togogenome.org/gene/10090:Atxn1l ^@ http://purl.uniprot.org/uniprot/P0C7T6 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATXN1 family.|||Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression (By similarity). Can suppress the cytotoxicity of ATXN1 in spinocerebellar ataxia type 1 (SCA1) (PubMed:16121196). In concert with CIC and ATXN1, involved in brain development (PubMed:28288114).|||Expressed in the cortex and hypothalamus (at protein level). Expressed in neuronal cells. Highly expressed in Purkinje cells of cerebellum.|||Homodimer. Interacts (via AXH domain) with NCOR2 (By similarity). Interacts with ATXN1 and CIC. Directly interacts with RBPJ; this interaction is disrupted in the presence of Notch intracellular domain. Competes with ATXN1 for RBPJ-binding (By similarity). Found in a complex with CIC and ATXN1 (PubMed:28288114).|||Its overexpression suppresses the ataxia caused by polyglutamine-expanded Atxn1. Competes with mutant Atxn1 and wild-type Atxn1 for association with CIC. Decreased association of mutant Atxn1 into its CIC-containing complexes decreases the levels of mutant Atxn1-containing CIC complexes, suppressing pathology, while promoting aggregation and thus increasing nuclear inclusions.|||Mice with conditional knockouts of either ATXN1-ATXN1L or CIC in the developing forebrain exhibit intellectual disability, hyperactivity, social-behavioral deficits and reduced thickness of upper cortical layers.|||Nucleus|||dendrite http://togogenome.org/gene/10090:Atp1b1 ^@ http://purl.uniprot.org/uniprot/P14094|||http://purl.uniprot.org/uniprot/Q3TV47|||http://purl.uniprot.org/uniprot/Q545P0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the X(+)/potassium ATPases subunit beta family.|||Cell membrane|||Expressed in cardiac muscle and in flexor digitorum brevis (FDB) muscle (at protein level) (PubMed:23392350). Expressed in a circadian manner in the kidney and aorta (at protein level) (PubMed:30012868).|||Glutathionylated (PubMed:21454534). N-glycosylated (By similarity).|||Involved in cell adhesion and establishing epithelial cell polarity.|||Membrane|||The C-terminal lobe folds into an immunoglobulin-like domain and mediates cell adhesion properties.|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with catalytic subunit ATP12A (By similarity). Interacts with regulatory subunit FXYD1 (By similarity). Interacts with regulatory subunit FXYD3 (PubMed:15743908). Interacts with NKAIN1, NKAIN2 and NKAIN4 (PubMed:17606467). Interacts with MLC1 (By similarity). Part of a complex containing MLC1, TRPV4, AQP4 and HEPACAM (By similarity). Interacts with KIRREL3 (By similarity). Interacts with OBSCN (via protein kinase domain 1) (PubMed:23392350).|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane.|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.|||sarcolemma http://togogenome.org/gene/10090:Cdkn2d ^@ http://purl.uniprot.org/uniprot/Q60773 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.|||Cytoplasm|||Interacts strongly with CDK4 and CDK6 and inhibits them.|||Interacts with CDK6.|||Nucleus http://togogenome.org/gene/10090:Stam ^@ http://purl.uniprot.org/uniprot/P70297|||http://purl.uniprot.org/uniprot/Q3TQ49 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STAM family.|||Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS (PubMed:19278655). Probably part of a complex at least composed of HSG, STAM and EPS15 (By similarity). Found in a complex with HGS and E3 ligase ITCH and DTX3L (By similarity). Interacts with E3 ligase DTX3L; the interaction brings together STAM and HSG, promotes their recruitment to early endosomes and decreases STAM and HGS ubiquitination by ITCH (By similarity). Interacts with STAMBP/AMSH (By similarity). Interacts with PDGFRB (By similarity). Interacts with LITAF; the interaction is direct (By similarity). Identified in a complex with HGS and LITAF (By similarity). Interacts with HAVCR1 (By similarity).|||Cytoplasm|||Early endosome membrane|||Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity).|||Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.|||Mice display disappearance of hippocampal CA3 pyramidal neurons as well as growth retardation in the third week after birth. Adult mice lacking Stam and Stam2 due to inducible gene targeting exhibit significant reduction in T-cell development in the thymus and profound reduction in the peripheral mature T-cells.|||No change during brain development.|||Phosphorylated on Tyr-198. Phosphorylated in response to IL2, IL3, IL4, IL7, CSF2/GM-CSF, EGF and PDGFB. Phosphorylated by activated PDGFRB (By similarity).|||The VHS domain mediates high-avidity binding to Lys63-linked and Lys48-linked polyubiquitinated cargos.|||Ubiquitinated by ITCH.|||Ubiquitously expressed. Enriched expression in synaptic vesicles. http://togogenome.org/gene/10090:Mmrn2 ^@ http://purl.uniprot.org/uniprot/A6H6E2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Heteromer of p110, p125, p140 and p200 subunits; disulfide-linked. Interacts with VEGFA.|||Inhibits endothelial cells motility and acts as a negative regulator of angiogenesis; it down-regulates KDR activation by binding VEGFA.|||N- and O-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Eml1 ^@ http://purl.uniprot.org/uniprot/D3Z4J9|||http://purl.uniprot.org/uniprot/Q05BC3 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat EMAP family.|||Contains a tandem atypical propeller in EMLs (TAPE) domain. The N-terminal beta-propeller is formed by canonical WD repeats; in contrast, the second beta-propeller contains one blade that is formed by discontinuous parts of the polypeptide chain.|||Cytoplasm|||Defects in Eml1 are the cause of the neuronal heterotopia observed in HeCo mice. These mice display heterotopic neurons in the rostro-medial part of the neocortex, together with epilepsy and subtle learning deficits in adults. At 17 dpc both Tbr1(+) and Cux1(+) neurons contribute to the heterotopia. Three days after birth, most Tbr1(+) have reached their final destination, but many Cux1(+) neurons remain in the heterotopia and fail to reach cortical layers II to IV, contrary to the situation in wild-type. Besides, progenitor cells continue to proliferate, resulting in large numbers of abnormally positioned actively proliferating cells during both early and late stages of corticogenesis. In HeCo mice, insertion of a retrotransposon into Eml1 leads to the absence of full-length Eml1 transcripts.|||Detected from 13.5 dpc to the first day after birth in cortical neuron progenitor cells in the ventricular zone and in postmitotic neurons in the cortical plate.|||Detected in adult brain cortex, hippocampus and thalamus (PubMed:24859200). Expressed in the stomach, lungs and in Sertoli cells of the testis (PubMed:31112734).|||Homotrimer; self-association is mediated by the N-terminal coiled coil (By similarity). Does not interact with EML3 (By similarity). Binds unpolymerized tubulins via its WD repeat region (By similarity). Binds repolymerizing microtubules (PubMed:24859200). Interacts with TASOR (PubMed:31112734).|||Modulates the assembly and organization of the microtubule cytoskeleton, and probably plays a role in regulating the orientation of the mitotic spindle and the orientation of the plane of cell division. Required for normal proliferation of neuronal progenitor cells in the developing brain and for normal brain development. Does not affect neuron migration per se.|||The N-terminal coiled coil is required for association with microtubules.|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Bag1 ^@ http://purl.uniprot.org/uniprot/Q60739 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Co-chaperone for HSP70 and HSC70 chaperone proteins (PubMed:9873016). Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli (By similarity).|||Cytoplasm|||Homodimer. Forms a heteromeric complex with HSP70/HSC70. Binds to the ATPase domain of HSP/HSC70 chaperones. Interacts with NR3C1. Interacts with the N-terminal region of MAPRE2. Interacts with PPP1R15A. Interacts with BCL2 in an ATP-dependent manner. Interacts with SIAH1, HSPA8 (via NBD), HSPA1A (via NBD) and HSPA1B (via NBD) (By similarity). Interacts with SIAH2 (PubMed:11257006).|||Isoform 2 is expressed in the heart, lung, kidney and spinal cord. Isoform 1 and isoform 2 are expressed in hematopoietic cell lines. The levels of isoform 2 are relatively constant in all the cell lines examined while the levels of isoform 1 are more variable (at protein level). Isoform 1 is expressed in the lung and kidney. Isoform 2 is expressed in various tissues, with highest levels in testis and stomach.|||Nucleus|||Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Rpl41 ^@ http://purl.uniprot.org/uniprot/P62947 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL41 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Interacts with the beta subunit of protein kinase CKII and stimulates phosphorylation of DNA topoisomerase II alpha by CKII (By similarity).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Akap5 ^@ http://purl.uniprot.org/uniprot/D3YVF0|||http://purl.uniprot.org/uniprot/H3BIV5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with ADCY8, and enhances its phosphorylation at lipid rafts. Binds dimer of the RII-beta regulatory subunit of cAMP-dependent protein kinase (By similarity).|||Membrane|||Multivalent scaffold protein that anchors the cAMP-dependent protein kinase/PKA to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors. Association with the beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR signaling pathway, but also the activation by PKA by switching off the beta2-AR signaling cascade. Plays a role in long term synaptic potentiation by regulating protein trafficking from the dendritic recycling endosomes to the plasma membrane and controlling both structural and functional plasticity at excitatory synapses.|||Palmitoylated. Palmitoylation at Cys-36 and Cys-123 play a key role in the targeting of AKAP5 to lipid rafts. Palmitoylation by ZDHHC2 is required for AKAP5 function in LTP-stimulated recycling endosome exocytosis.|||Postsynaptic recycling endosome membrane|||RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.|||The N-terminal region, which is highly basic, is required for interaction with calmodulin. http://togogenome.org/gene/10090:Mgp ^@ http://purl.uniprot.org/uniprot/P19788 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation.|||Belongs to the osteocalcin/matrix Gla protein family.|||Requires vitamin K-dependent gamma-carboxylation for its function.|||Secreted http://togogenome.org/gene/10090:Rif1 ^@ http://purl.uniprot.org/uniprot/Q6PR54 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RIF1 family.|||Chimeric cDNA.|||Chromosome|||Embryonic lethality in inbred 129/Ola and outbred MF1 mouse strains: 7.5 dpc embryos display significant developmental retardation (PubMed:23333305). Female-specific lethality in a CD1 strain background, while males survive (PubMed:23333305). Surviving males grow normally, are fertile, but are subject to infections due to defects in the immune response (PubMed:23333305). Surviving males are severely compromised for TP53BP1-dependent class-switch recombination (CSR) and fusion of dysfunctional telomeres (PubMed:23333305).|||Expressed in Sertoli cells, prospermatagonia, early primary spermatocytes, and in oocytes at all stages of their growth. Expressed in embryonic stem (ES) and embryonic germ (EG) cells: expression is lost upon differentiation.|||Found in the nucleus of germinal-vesicle (GV) stage oocytes prior to fertilization. Accumulates in the male and female pronucleus after fertilization. Expressed in the nuclei of all blastomeres from the two cell stage to the compacted morula stage, although absent from the polar body and inner cell mass (ICM). Found in the nuclei of polar and mural trophectoderm cells from 3.5 dpc, and at high levels in the epiblast from 5.5 dpc to 7.5 dpc. Expressed by primitive germ cells (PGCs) in both male and female from 9.5 dpc to 13.5 dpc, at which point expression declines. A low level is observed in Sertoli cells of the testis at 17.5 dpc.|||Interacts with TP53BP1 (when phosphorylated by ATM) (PubMed:23333305, PubMed:23306437, PubMed:23306439). May interact with TRF2 (PubMed:15042697). Interacts with SHLD2 (By similarity). Interacts with ERCC6 (via WHD region) (By similarity).|||Intron retention.|||Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:23333305, PubMed:23306437, PubMed:23306439). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333305, PubMed:23306437, PubMed:23306439). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (By similarity). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333305, PubMed:23306437). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333305, PubMed:23306437). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23333305, PubMed:23333306, PubMed:23306439). Promotes NHEJ of dysfunctional telomeres (PubMed:23333305).|||May be due to a competing acceptor splice site.|||Nucleus|||spindle|||telomere http://togogenome.org/gene/10090:Gad1 ^@ http://purl.uniprot.org/uniprot/P48318|||http://purl.uniprot.org/uniprot/Q548L6 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the group II decarboxylase family.|||Catalyzes the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with pyridoxal 5'-phosphate as cofactor.|||Deficient mice die at birth with cleft palate and apnea and exhibit reduced levels of glutamic acid decarboxylase and gamma-aminobutyric acid in the cerebral cortex.|||Homodimer. http://togogenome.org/gene/10090:H2-DMb1 ^@ http://purl.uniprot.org/uniprot/Q31094 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Ubap2l ^@ http://purl.uniprot.org/uniprot/A0A0G2JDV6|||http://purl.uniprot.org/uniprot/A0A0H2UH17|||http://purl.uniprot.org/uniprot/Q80X50|||http://purl.uniprot.org/uniprot/Q8BJ53 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Cytoplasm|||Interacts with BMI1. Part of a complex consisting of UBAP2L, BMI1 and RNF2. Interacts with G3BP1 (via NTF2 domain); promoting stress granule formation.|||Nucleus|||Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (By similarity). Plays an important role in the activity of long-term repopulating hematopoietic stem cells (LT-HSCs) (PubMed:25185265). Required for efficient formation of stress granules (By similarity).|||Stress granule http://togogenome.org/gene/10090:Eps8 ^@ http://purl.uniprot.org/uniprot/Q08509|||http://purl.uniprot.org/uniprot/Q3U2Z5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EPS8 family.|||Expressed in neuronal cell body and neurites, and prominently enriched in the axonal growth cone (PubMed:19564905). Expressed at the tips of cochlear hair cells stereocilia (PubMed:23918390).|||Homodimer. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with BAIAP2. Interacts with SHB and LANCL1. Interacts with EGFR; mediates EPS8 phosphorylation. Interacts with MYO15A and WHRN.|||No visible phenotype. Defects in PDGF-induced membrane ruffling due to defects in Ras to Rac signals. Dendritic cells are impaired in directional and chemotactic migration and are delayed in reaching the draining lymph node in vivo after inflammatory challenge. Mice show short stereocilia.|||Phosphorylation at Ser-624 and Thr-628 by MAPK following BDNF treatment promotes removal from actin and filopodia formation. Phosphorylated by several receptor tyrosine kinases.|||Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes.|||The SH3 domain mediates interaction with SHB.|||The effector region is required for activating the Rac-specific guanine nucleotide exchange factor (GEF) activity (PubMed:11524436). It mediates both barbed-end actin capping and actin bundling activities (PubMed:20532239). The capping activity is mediated by an amphipathic helix that binds within the hydrophobic pocket at the barbed ends of actin blocking further addition of actin monomers, while the bundling activity is mediated by a compact 4 helix bundle, which contacts 3 actin subunits along the filament (PubMed:20532239).|||Ubiquitinated by the SCF(FBXW5) E3 ubiquitin-protein ligase complex during G2 phase, leading to its transient degradation and subsequent cell shape changes required to allow mitotic progression. Reappears at the midzone of dividing cells.|||cell cortex|||growth cone|||ruffle membrane|||stereocilium|||synaptosome http://togogenome.org/gene/10090:Cnppd1 ^@ http://purl.uniprot.org/uniprot/Q8K158 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CNPPD1 family.|||Membrane http://togogenome.org/gene/10090:Fkbp14 ^@ http://purl.uniprot.org/uniprot/P59024 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum lumen|||Inhibited by tacrolimus/FK506.|||Monomer. Homodimer. Interacts with type III, type IV and type X collagens.|||PPIase which accelerates the folding of proteins during protein synthesis. Has a preference for substrates containing 4-hydroxylproline modifications, including type III collagen. May also target type VI and type X collagens. http://togogenome.org/gene/10090:Clk4 ^@ http://purl.uniprot.org/uniprot/O35493|||http://purl.uniprot.org/uniprot/Q4FJV9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylates on all three types of residues.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.|||Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.|||Expressed in the hippocampus, the cerebellum and the olfactory bulb.|||Interacts with UBL5.|||Nucleus|||TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins. http://togogenome.org/gene/10090:Cyp2c50 ^@ http://purl.uniprot.org/uniprot/Q91X77 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in heart and liver.|||Metabolizes arachidonic acid to several midchain and omega-terminal hydroxyeicosatetraenoic acids (HETE).|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Chat ^@ http://purl.uniprot.org/uniprot/Q8BQV2 ^@ Similarity ^@ Belongs to the carnitine/choline acetyltransferase family. http://togogenome.org/gene/10090:Mfap4 ^@ http://purl.uniprot.org/uniprot/Q9D1H9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Could be involved in calcium-dependent cell adhesion or intercellular interactions. May contribute to the elastic fiber assembly and/or maintenance.|||Homodimer. Can also form higher oligomers. Interacts with FBN1, FBN2 and LOX. Interacts with COL1A1 in a Ca (2+)-dependent manner. Interacts with ELN in a Ca (2+)-dependent manner; this interaction promotes ELN self-assembly.|||extracellular matrix http://togogenome.org/gene/10090:Gpn2 ^@ http://purl.uniprot.org/uniprot/A2A9F7|||http://purl.uniprot.org/uniprot/Q8VEJ1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the GPN-loop GTPase family.|||Binds to RNA polymerase II (RNAPII).|||Heterodimers with GPN1 or GPN3. Binds to RNA polymerase II (RNAPII).|||Small GTPase required for proper localization of RNA polymerase II and III (RNAPII and RNAPIII). May act at an RNAP assembly step prior to nuclear import. http://togogenome.org/gene/10090:Ltbr ^@ http://purl.uniprot.org/uniprot/B2RRV3|||http://purl.uniprot.org/uniprot/P50284 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for the heterotrimeric lymphotoxin containing LTA and LTB, and for TNFS14/LIGHT. Promotes apoptosis via TRAF3 and TRAF5. May play a role in the development of lymphoid organs (By similarity).|||Self-associates (By similarity). Associates with TRAF5. Associates with TRAF3 and TRAF4 (By similarity). http://togogenome.org/gene/10090:Hs3st1 ^@ http://purl.uniprot.org/uniprot/O35310 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 1 family.|||Golgi apparatus lumen|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan (PubMed:9346953, PubMed:15060080). Catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact) (PubMed:9346953, PubMed:15060080). This modification is a crucial step in the biosynthesis of anticoagulant heparan sulfate as it completes the structure of the antithrombin pentasaccharide binding site (PubMed:9346953, PubMed:15060080). http://togogenome.org/gene/10090:Pelp1 ^@ http://purl.uniprot.org/uniprot/A0A158SIT8|||http://purl.uniprot.org/uniprot/Q9DBD5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RIX1/PELP1 family.|||Coactivator of estrogen receptor-mediated transcription and a corepressor of other nuclear hormone receptors and sequence-specific transcription factors. Plays a role in estrogen receptor (ER) genomic activity when present in the nuclear compartment by activating the ER target genes in a hormonal stimulation dependent manner. Can facilitate ER non-genomic signaling via SRC and PI3K interaction in the cytosol. Plays a role in E2-mediated cell cycle progression by interacting with RB1. May have important functional implications in ER/growth factor cross-talk. Interacts with several growth factor signaling components including EGFR and HRS. Functions as the key stabilizing component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit. Regulates pre-60S association of the critical remodeling factor MDN1 (By similarity).|||Cytoplasm|||Interacts with HRS, RXRA, SUMO2, HDAC2, RB1 and STAT3. Interacts with PI3K, SRC and EGFR in cytoplasm. Interacts with ESR1, the interaction is enhanced by 17-beta-estradiol; the interaction increases ESR1 transcriptional activity (By similarity). Interacts with CREBBP and EP300 in a ligand-dependent manner (By similarity). Forms two complexes in the presence of 17-beta-estradiol; one with SRC and ESR1 and another with LCK and ESR1. Interacts with histone H1 and H3 with a greater affinity for H1. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity). Core component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9 (PubMed:22872859). Interacts with BCAS3 (By similarity). Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts (via PELP1) with MDN1 (via its hexameric AAA ATPase ring) and the pre-60S ribosome particles (By similarity).|||Nucleus|||The Glu-rich region mediates histones interaction.|||The Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are required for the association with nuclear receptor ESR1.|||Transiently sumoylated, preferentially conjugated to SUMO2 or SUMO3. Sumoylation causes nucleolar exclusion of PELP1 and promotes the recruitment of MDN1 to pre-60S particles. Desumoylation by SUMO isopeptidase SENP3 is needed to release both PELP1 and MDN1 from pre-ribosomes.|||Widely expressed with high levels in testis, ovary, uterus and pituitary gland.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Nol10 ^@ http://purl.uniprot.org/uniprot/Q3TUB5|||http://purl.uniprot.org/uniprot/Q5RJG1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat NOL10/ENP2 family.|||nucleolus http://togogenome.org/gene/10090:Sult2a5 ^@ http://purl.uniprot.org/uniprot/K7N6K9 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Cpvl ^@ http://purl.uniprot.org/uniprot/Q9D3S9 ^@ Function|||Similarity ^@ Belongs to the peptidase S10 family.|||May be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation. http://togogenome.org/gene/10090:Gm10147 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Rbpms2 ^@ http://purl.uniprot.org/uniprot/Q8VC52 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Interacts with EEF2.|||RNA-binding protein involved in the regulation of smooth muscle cell differentiation and proliferation in the gastrointestinal system (By similarity). Binds NOG mRNA, the major inhibitor of the bone morphogenetic protein (BMP) pathway. Mediates an increase of NOG mRNA levels, thereby contributing to the negative regulation of BMP signaling pathway and promoting reversible dedifferentiation and proliferation of smooth muscle cells (By similarity). http://togogenome.org/gene/10090:Septin11 ^@ http://purl.uniprot.org/uniprot/A0A0J9YUL3|||http://purl.uniprot.org/uniprot/Q8C1B7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Expressed in the cerebral cortex (at protein level).|||Filament-forming cytoskeletal GTPase.|||Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). May play a role in the cytoarchitecture of neurons, including dendritic arborization and dendritic spines, and in GABAergic synaptic connectivity (By similarity).|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules (By similarity). Forms homooligomers (By similarity). GTPase activity is required for filament formation (By similarity). Interacts with SEPTIN7, SEPTIN9 and SEPTIN12 (By similarity).|||Septins polymerize into heterooligomeric protein complexes that form filaments.|||Synapse|||axon|||cytoskeleton|||dendritic spine http://togogenome.org/gene/10090:4933434E20Rik ^@ http://purl.uniprot.org/uniprot/Q05D39|||http://purl.uniprot.org/uniprot/Q8R092 ^@ Domain|||Function|||Subcellular Location Annotation ^@ General regulator of phagocytosis. Required to uptake Gram negative bacterium by macrophages.|||Golgi apparatus|||Membrane|||Mitochondrion|||N-terminal region is required for phagocytosis of Gram negative bacterium. http://togogenome.org/gene/10090:Zfp710 ^@ http://purl.uniprot.org/uniprot/Q3U288 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Gtf2h4 ^@ http://purl.uniprot.org/uniprot/O70422|||http://purl.uniprot.org/uniprot/Q542U3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFB2 family.|||Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription.|||Component of the general transcription and DNA repair factor IIH (TFIIH) core complex which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA.|||Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.|||Nucleus http://togogenome.org/gene/10090:Or10d5 ^@ http://purl.uniprot.org/uniprot/Q8VG91 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ms4a3 ^@ http://purl.uniprot.org/uniprot/Q3TYT4|||http://purl.uniprot.org/uniprot/Q53ZU3|||http://purl.uniprot.org/uniprot/Q920C4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed at low levels only in specific immune tissues, such as, spleen, bone marrow and peripheral blood leukocytes.|||Hematopoietic modulator for the G1-S cell cycle transition. Modulates the level of phosphorylation of cyclin-dependent kinase 2 (CDK2) through its direct binding to cyclin-dependent kinase inhibitor 3 (CDKN3/KAP) (By similarity).|||Interacts with CDKN3. Interacts with CDKN3-CDK2 complexes through its binding to CDKN3; this interaction facilitates dissociation of cyclin A from CDKN3-CDK2 complexes (By similarity).|||Membrane|||The C-terminal region is required for binding to CDKN3-CDK2 complexes and the modulation of CDKN3 activity. http://togogenome.org/gene/10090:Fbl ^@ http://purl.uniprot.org/uniprot/P35550 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by CREBBP/CBP, preventing methylation of 'Gln-105' of histone H2A (H2AQ104me), without affecting rRNA methylation. Deacetylation by SIRT7 restores methylation of 'Gln-105' of histone H2A (H2AQ104me).|||Belongs to the methyltransferase superfamily. Fibrillarin family.|||By homology to other fibrillarins, some or all of the N-terminal domain arginines are modified to asymmetric dimethylarginine (DMA).|||Component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles that contain SNU13, FBL, NOP5 and NOP56, plus a guide RNA. It is associated with the U3, U8, U13, X and Y small nuclear RNAs. Component of several ribosomal and nucleolar protein complexes. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity). Interacts with PRMT5 and UTP20. Interacts with DDX5 and C1QBP. Interacts with NOL11. Interacts with PIH1D1. Interacts with RRP1B (By similarity). Interacts with NOLC1 (By similarity). Interacts with SDE2 (By similarity).|||S-adenosyl-L-methionine-dependent methyltransferase that has the ability to methylate both RNAs and proteins (PubMed:32017896). Involved in pre-rRNA processing by catalyzing the site-specific 2'-hydroxyl methylation of ribose moieties in pre-ribosomal RNA (By similarity). Site specificity is provided by a guide RNA that base pairs with the substrate (By similarity). Methylation occurs at a characteristic distance from the sequence involved in base pairing with the guide RNA (By similarity). Probably catalyzes 2'-O-methylation of U6 snRNAs in box C/D RNP complexes (PubMed:32017896). U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (PubMed:32017896). Also acts as a protein methyltransferase by mediating methylation of 'Gln-105' of histone H2A (H2AQ104me), a modification that impairs binding of the FACT complex and is specifically present at 35S ribosomal DNA locus (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Ppat ^@ http://purl.uniprot.org/uniprot/Q3UGA8|||http://purl.uniprot.org/uniprot/Q8CIH9 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Binds 1 Mg(2+) ion per subunit.|||Binds 1 [4Fe-4S] cluster per subunit.|||Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine.|||Homotetramer.|||In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family. http://togogenome.org/gene/10090:Arfgap3 ^@ http://purl.uniprot.org/uniprot/Q9D8S3 ^@ Activity Regulation|||Function|||Subcellular Location Annotation ^@ Cytoplasm|||GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2).|||GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes (By similarity).|||Golgi apparatus membrane http://togogenome.org/gene/10090:Phf23 ^@ http://purl.uniprot.org/uniprot/Q8BSN5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a negative regulator of autophagy, through promoting ubiquitination and degradation of LRSAM1, an E3 ubiquitin ligase that promotes autophagy in response to starvation or infecting bacteria.|||Belongs to the PHF23 family.|||Cytoplasm|||Interacts with LRSAM1.|||Nucleus|||The PHD-type zinc-finger domain is required for interaction with LRSAM1 and negative regulation of autophagy. http://togogenome.org/gene/10090:Dnajc11 ^@ http://purl.uniprot.org/uniprot/Q5U458 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex.|||Belongs to the DNAJC11 family.|||Following chemical mutagenesis predicted to give rise to a transcript subject to non-sense mediated deccay, mice exhibit an autosomal recessive neuromuscular disease and abnormal mitochondrial cristae morphology.|||Mitochondrion|||Mitochondrion outer membrane|||Probable cloning artifact.|||Required for mitochondrial inner membrane organization. Seems to function through its association with the MICOS complex and the mitochondrial outer membrane sorting assembly machinery (SAM) complex. http://togogenome.org/gene/10090:Rassf4 ^@ http://purl.uniprot.org/uniprot/Q8CB96 ^@ Function|||Subunit ^@ Interacts directly with activated KRAS in a GTP-dependent manner.|||Potential tumor suppressor. May act as a KRAS effector protein. May promote apoptosis and cell cycle arrest. http://togogenome.org/gene/10090:Zranb2 ^@ http://purl.uniprot.org/uniprot/B2RRT9|||http://purl.uniprot.org/uniprot/D3Z4U0|||http://purl.uniprot.org/uniprot/Q9R020 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZRANB2 family.|||Interacts with the C-terminal half of SNRNP70, the Arg/Ser-rich domain of AKAP17A as well as with U2AF1 and CLK1.|||Nucleus|||Splice factor required for alternative splicing of TRA2B/SFRS10 transcripts. May interfere with constitutive 5'-splice site selection (By similarity).|||Splice factor required for alternative splicing of TRA2B/SFRS10 transcripts. May interfere with constitutive 5'-splice site selection.|||The RanBP2-type zinc fingers mediate binding to RNA. http://togogenome.org/gene/10090:Cryge ^@ http://purl.uniprot.org/uniprot/A2RTH4|||http://purl.uniprot.org/uniprot/Q03740 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Detected in the superior olivary complex of the auditory hindbrain.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||In the embryo, expressed by day 12 of gestation. Maximum levels are found at day 30-40 followed by a rapid decline.|||There are six different gamma crystallins identified in mouse lens. http://togogenome.org/gene/10090:Or52e15 ^@ http://purl.uniprot.org/uniprot/Q8VG28 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc35f1 ^@ http://purl.uniprot.org/uniprot/Q8BGK5 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC35F solute transporter family.|||Chimeric cDNA.|||Putative solute transporter.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Serpinb3c ^@ http://purl.uniprot.org/uniprot/A2RSF9|||http://purl.uniprot.org/uniprot/Q9D1E7 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Pmvk ^@ http://purl.uniprot.org/uniprot/Q3THA3|||http://purl.uniprot.org/uniprot/Q9D1G2 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the reversible ATP-dependent phosphorylation of mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key step in the mevalonic acid mediated biosynthesis of isopentenyl diphosphate and other polyisoprenoid metabolites.|||Monomer.|||Was originally thought to be located in the peroxisome. However, was later shown to be cytosolic.|||cytosol http://togogenome.org/gene/10090:Or2d2b ^@ http://purl.uniprot.org/uniprot/E9Q725 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or9g3 ^@ http://purl.uniprot.org/uniprot/Q8VFJ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fn3krp ^@ http://purl.uniprot.org/uniprot/Q8K274 ^@ Domain|||Function|||Similarity ^@ Belongs to the fructosamine kinase family.|||Ketosamine-3-kinase involved in protein deglycation by mediating phosphorylation of ribuloselysine and psicoselysine on glycated proteins, to generate ribuloselysine-3 phosphate and psicoselysine-3 phosphate, respectively (PubMed:14633848). Ribuloselysine-3 phosphate and psicoselysine-3 phosphate adducts are unstable and decompose under physiological conditions (PubMed:14633848). Not able to phosphorylate fructoselysine (PubMed:14633848).|||The ATP-binding domain is structurally related to aminoglycoside phosphotransferase family. http://togogenome.org/gene/10090:Armh4 ^@ http://purl.uniprot.org/uniprot/Q8BT18 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in bone-marroew cells.|||Interacts with IL6ST; this interaction prevents IL6ST protein homodimerization and bridges ARMH4 with IL6R and STAT3 and therefore inhibits phosphorylation of STAT3 at 'Tyr-705' (By similarity). Interacts (via cytoplasmic tail) with RICTOR; this interaction bridges ARMH4 to the mTORC2 complex and inhibits the mTORC2 kinase activity (PubMed:25418727).|||May modulate immune response and may play a role in inflammation. Down-modulates STAT3 signaling throught direct interaction with IL6ST, resulting in the inhibition of phosphorylation of STAT3 at 'Tyr-705' (PubMed:26927669). May negatively regulates AKT signaling by modulating the activity of mTORC2 complex through RICTOR interaction (PubMed:25418727).|||Membrane|||Transcriptionally regulated by FOXO3. http://togogenome.org/gene/10090:Fxr2 ^@ http://purl.uniprot.org/uniprot/Q6P5B5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FMR1 family.|||Cytoplasmic ribonucleoprotein granule|||Postsynapse|||Synapse http://togogenome.org/gene/10090:Cypt1 ^@ http://purl.uniprot.org/uniprot/Q8CH20 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected from 29 days postpartum onwards, with increasing expression through to the adult stage.|||Specifically expressed in spermatozoa (at protein level). Detected from the elongated spermatid stage onwards; not found in immature germ cells or somatic cells (at protein level).|||perinuclear theca http://togogenome.org/gene/10090:Tmem229b ^@ http://purl.uniprot.org/uniprot/Q8BFQ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM229 family.|||Membrane http://togogenome.org/gene/10090:Tmprss12 ^@ http://purl.uniprot.org/uniprot/Q3V0Q7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Exclusively expressed in the testis, from spermatocytes to elongated spermatids (at protein level).|||Initially expressed in the testis at 10 days of age, expression increases until 2 weeks of age whereafter protein abundance remains consistent (at protein level).|||Male mice are infertile (PubMed:32529245, PubMed:35547804). Decrease in sperm count and sperm motility, as a result of decreased numbers of pachytene spermatocytes, diplotene spermatocytes, round spermatids and elongated spermatids (PubMed:35547804). Increase in the rate of apoptosis among spermatocytes accompanied by abnormal chromosomal synapsis and failure of double-strand break repair during meiosis in the testis (PubMed:35547804). Increase in the number of sperm with abnormal mitochondria that show blurred or absent inner mitochondrial membrane cristae with decreased ATP content and oxygen consumption, together with a decrease in expression of key markers of oxidative phosphorylation such as Mtatp6/MTATP and Cstb/MTCYB (PubMed:35547804). Ejaculated sperm fail to migrate from the uterus to the oviduct due to significantly reduced sperm motility (PubMed:32529245). Spermatozoa binding to the zona pellucida is significantly reduced in vitro, resulting in a loss of fertilization, this can be rescued via weakening of the zona pellucida (PubMed:32529245). Decrease in mature ADAM3 protein in spermatozoa but normal levels are seen in testicular germ cells (PubMed:32529245). In the testis there is a decrease in abundance of proteins involved in meiosis, apoptosis, mitochondrial function and cell adhesion such as Klc3, Rad51, Bccip, Pgam2 and Mgst1 (PubMed:35547804).|||Required for male fertility (PubMed:32529245, PubMed:35547804). Plays a critical role in sperm capacitation and acrosome reactions during fertilization, and also plays a role in the regulation of proteins involved in spermatogenesis (PubMed:35547804). Regulates protein pathways that promote chromosomal synapsis formation, double-strand break repair, formation of the inner mitochondrial membrane cristae and apoptosis in developing sperm (PubMed:35547804). Required for normal sperm motility and binding to the zona pellucida, potentially via a role in ADAM3 protein maturation (PubMed:32529245).|||acrosome http://togogenome.org/gene/10090:Nxf7 ^@ http://purl.uniprot.org/uniprot/Q80SZ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NXF family.|||Cytoplasm|||nucleoplasm http://togogenome.org/gene/10090:Reg3g ^@ http://purl.uniprot.org/uniprot/O09049 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a hormone in response to different stimuli like anti-inflammatory signals, such as IL17A, or gut microbiome. Is secreted by different cell types to activate its receptor EXTL3 and induce cell specific signaling pathways (PubMed:36240758, PubMed:22727489, PubMed:27830702). Induced by IL17A in keratinocytes, regulates keratinocyte proliferation and differentiation after skin injury (PubMed:22727489). In parallel, inhibits skin inflammation through the inhibition of inflammatory cytokines such as IL6 and TNF (PubMed:27830702). Induced by IL22 in lung epithelial cells, inhibits cytokine production and regulates allergic airway inflammation (PubMed:28811323). Induced in small intestine by inulin-enriched diet and Lactobacillus gasseri enriched microbiome, plays a role in the improvement of gut barrier function, the regulation of energy balance and glucose levels. Modulates microbiota composition in duodenal contents (PubMed:36240758). Produced by nociceptor in response to endotoxins, prevents endotoxic death by targeting kynurenine pathway in microglia (PubMed:35263589).|||Bactericidal C-type lectin which acts exclusively against Gram-positive bacteria and mediates bacterial killing by binding to surface-exposed carbohydrate moieties of peptidoglycan. Restricts bacterial colonization of the intestinal epithelial surface and consequently limits activation of adaptive immune responses by the microbiota.|||Cytoplasm|||Forms a hexameric membrane-permeabilizing oligomeric pore on membrane phospholipids. The hexamer is formed by three dimers related by helical symmetry. Forms filaments, filamentation traps pore complexes and limits damage to host cells. Interacts with EXTL3.|||Has bactericidal activity against L.monocytogenes and methicillin-resistant S.aureus.|||Has bacteriostatic activity.|||In mid-small intestine, very low levels at birth. Expression levels rise dramatically during the weaning period (P17-P22) and remain high into adulthood in conventionally raised but not germfree animals.|||Lipopolysaccharide inhibits pore-forming activity, explaining why is bactericidal for Gram-positive but not Gram-negative bacteria.|||Mutant mice are born at normal Mendelian ratios. They appear healthy and show no signs of enteropathy, but exhibit marked increase in the number of mucosa-associated bacteria, predominantly Gram-positive, relative to cohoused wild-type littermates in distal small intestine (PubMed:21998396). Nociceptor-specific deficient mice exhibit high mortality rates in response to endotoxin accompanied by increased kynurenine pathway and impaired ATP production in the brain (PubMed:35263589).|||Predominantly expressed in the small intestine, including Paneth cells (at protein level). Hardly detectable in the colon (at protein level) (PubMed:16504538, PubMed:16931762, PubMed:17635956, PubMed:21998396). Highly expressed in the lung epithelium during methicillin-resistant S.aureus infection and allergic airway inflammation (at protein level) (PubMed:28811323). Skin injury increases its epidermal expression (PubMed:27830702, PubMed:22727489, PubMed:23401489). Also expressed in the pancreas (PubMed:9055810). Expressed by nocireceptors (PubMed:35263589).|||Proteolytic processing by trypsin removes an inhibitory N-terminal propeptide and is essential for peptidoglycan binding and antibacterial activity.|||Secreted|||The EPN motif is essential for recognition of the peptidoglycan carbohydrate backbone and for efficient bacterial killing with Glu-114 playing a key role in peptidoglycan binding and bactericidal activity.|||Up-regulated in Paneth cells by intestinal microbiota (at protein level) (PubMed:16931762). MyD88-mediated signals are essential for its induction in intestinal epithelial cells (PubMed:17635956). Induction in the lung is dependent on IL6ST-induced STAT3 signaling (PubMed:23401489). IL17A and IL33 induces its expression in primary keratinocytes and skin wounds (PubMed:22727489, PubMed:27830702). IL22 induces its expression in lung epithelial cells (PubMed:28811323). Feeding with a fermentable fiber-enriched inulin diet increases expression in intestine (PubMed:36240758). Expressed by nociceptors in response to LPS (PubMed:35263589). http://togogenome.org/gene/10090:Crygc ^@ http://purl.uniprot.org/uniprot/A3RLD4|||http://purl.uniprot.org/uniprot/A3RLD5|||http://purl.uniprot.org/uniprot/Q61597 ^@ Domain|||Function|||Miscellaneous|||Similarity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||There are six different gamma crystallins identified in mouse lens. http://togogenome.org/gene/10090:Hoxc8 ^@ http://purl.uniprot.org/uniprot/P09025 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Antp homeobox family.|||Initially found in all tissues of the posterior region in 8.5 and 9.5 dpc. Embryos, it eventually become specifically located in neural tissue.|||Interacts with HOMEZ (By similarity). Forms a DNA-binding heterodimer with transcription factor PBX1 (PubMed:7791786).|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Tceal8 ^@ http://purl.uniprot.org/uniprot/Q9CZY2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TFS-II family. TFA subfamily.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Insyn2b ^@ http://purl.uniprot.org/uniprot/Q6GQV1 ^@ Similarity ^@ Belongs to the INSYN2 family. http://togogenome.org/gene/10090:Fos ^@ http://purl.uniprot.org/uniprot/P01101 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. Fos subfamily.|||Constitutively sumoylated with SUMO1, SUMO2 and SUMO3. Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 (By similarity).|||Endoplasmic reticulum|||Heterodimer; with JUN (PubMed:29272704). Component of the SMAD3/SMAD4/JUN/FOS complex required for synergistic TGF-beta-mediated transcription at the AP1 promoter site (By similarity). Interacts with SMAD3; the interaction is weak even on TGF-beta activation (By similarity). Interacts with MAFB (By similarity). Interacts with TSC22D3 (via N-terminus); this interaction inhibits the binding of active AP1 to its target DNA (PubMed:11397794). Interacts with CDS1 and PI4K2A, but not with CDIPT, nor PI4K2B (PubMed:22105363). Interacts (via bZIP domain and leucine-zipper region) with the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF) subunits SMARCB1, SMARCC2 and SMARCD1 (PubMed:29272704). Interacts (via bZIP domain and leucine-zipper region) with ARID1A (PubMed:29272704).|||In quiescent cells, the small amount of FOS present is phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated form is cytosolic. In growing cells, dephosphorylated by PTPN2. Dephosphorylation leads to the association with endoplasmic reticulum membranes and activation of phospholipid synthesis.|||Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling (By similarity). Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.|||Nucleus|||Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both Ser-362 and Ser-374 by MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation on Ser-374 being the major site for protein stabilization on NGF stimulation. Phosphorylation on Ser-362 and Ser-374 primes further phosphorylations on Thr-325 and Thr-331 through promoting docking of MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation. Phosphorylation on Ser-362 by RSK2 in osteoblasts contributes to osteoblast transformation (By similarity).|||cytosol http://togogenome.org/gene/10090:Sulf2 ^@ http://purl.uniprot.org/uniprot/Q8CFG0 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Cell surface|||Endoplasmic reticulum|||Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity (By similarity). It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin (By similarity).|||Glycosylation at Ser-588 negatively regulates its N-acetylglucosamine-6-sulfatase and arylsulfatase activities.|||Golgi stack|||Processing by furin produces a secreted form.|||Secreted|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Slc6a16 ^@ http://purl.uniprot.org/uniprot/A0A1L1SR47 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Sorcs2 ^@ http://purl.uniprot.org/uniprot/Q9EPR5 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VPS10-related sortilin family. SORCS subfamily.|||Cell membrane|||Cell projection|||Cytoplasmic vesicle membrane|||Detected in Purkinje cells and pyramidal neurons in brain cortex, cerebellum, dentate gyrus, striatum and hippocampus, and in glia cells in dorsal root ganglia (DRG) (PubMed:24908487, PubMed:27457814, PubMed:28469074, PubMed:30840898). Not detected in neurons from the dorsal root ganglia (PubMed:24908487). Detected in hair cells and supporting cells in the organ of Corti, utricuar maculae and cristae (at protein level) (PubMed:28346477). Detected in brain, lung and testis (PubMed:11165493). Detected in the inner ear in neonates (PubMed:28346477).|||Early endosome membrane|||Expression is highest in developing brain. Transiently expressed in all 3 germ layers (PubMed:11165493). Detected in midbrain, spinal cord, heart and lung at 15.5 dpc (PubMed:24908487). Coexpressed with NGFR in neurons in the ventral part of the hippocampus CA1 region at 23 and 30 days after birth. The number of neurons that coexpress SORCS2 and NGFR is increased 30 days after birth. SORCS2 and NGFR are no longer coexpressed in hippocampus neurons in 60 day old adults (PubMed:29909994).|||Gene disruption gives rise to contradictory results (PubMed:24908487, PubMed:27457814, PubMed:28469074, PubMed:28346477, PubMed:30840898). The majority of studies report normal body weight, normal startle responses to noise and relatively minor behavorial defects (PubMed:24908487, PubMed:27457814, PubMed:28469074, PubMed:30840898). Another publication finds that gene disruption gives rise to mice with strongly reduced body weight and profound deafness. Gene disruption was due to random insertion of a Cre construct under the control of the TEK promoter. Analysis of the genomic DNA showed that in 21 cases the Cre construct had inserted in an Ig kappa locus, and in 13 cases the construct had inserted into the first intron of the SORCS2 gene, leading to strongly reduced SORCS2 expression (PubMed:28346477). The reasons for these discrepancies are not clear, but may be due to the way the experiments were done. The fact that an identical phenotype was found when the Cre construct under the control of the TEK promoter had inserted in an Ig kappa locus suggests that there are additional, unidentified causes that play a role in the observed defects.|||Homodimer (in vitro) (PubMed:30061605). Heterodimer with NGFR (PubMed:22155786, PubMed:24908487, PubMed:27457814). The extracellular domains of the heterodimer bind the precursor form of NGF (proNGF) (PubMed:22155786). Can also bind mature NGF and BDNF. Each chain in the receptor dimer interacts (via extracellular domain) with an NGF dimer (in vitro) (PubMed:30061605). Interacts with the precursor forms of BDNF (proBDNF) and NTF3 (proNT3) (By similarity). The cytoplasmic region of the heterodimer formed by NGFR and SORCS2 binds TRIO. ProNGF binding mediates dissociation of TRIO from the receptor complex (By similarity). Interacts with SLC1A1 (PubMed:30840898). Interacts with VPS35. Interacts (via extracellular domain) with NTRK2 (via extracellular domain) (PubMed:27457814). Interacts with VPS35. Interacts (via extracellular domain) with GRIN2A (PubMed:28469074).|||Mice are viable and fertile and display no obvious phenotype, but their neurons do not display growth cone collapse in response to proBDNF (PubMed:24908487, PubMed:29909994). Cultured neurons from mutant mice display longer neurites than wild-type neurons, and the frontal cortex of 12 week old mice is hyperinnervated with fibers from tyrosine hydroxylase-positive neurons (PubMed:24908487, PubMed:29909994). Mutant mice display mildly increased spontaneous locomotor activity; contrary to wild-type, treatment with amphetamine decreases their locomotor activity. After sciatic nerve injury, 2 day old and adult mice show discreased Schwann cell apoptosis distal to the lesion (PubMed:24908487). Mutant mice show increased mortality after seizures caused by repeated treatments with the convulsant pentylenetetrazol (PTZ). Hippocampus neurons from mutant mice display increased levels of oxidative stress and increased apoptosis (PubMed:30840898). Mutant mice display subtle behavorial defects, with hyperactivity, altered acquisition of spatial memory, but a normal startle response to noise (PubMed:27457814). Heterozygous mice have normal body weight and motor skills, but combination with a mouse model for Huntington disease (HD) gives rise to increased severity of impaired motor skills (PubMed:28469074). After a cross of mice carrying a Cre construct under the control of the Tek promoter with mice carrying a floxed Nppc gene a subset of the offspring displayed behavorial defects, including hyperactivity and hanging from cage tops. A subset (11 out of 33 mice) displayed strongly reduced body weight and profound deafness, with defects in the organization of the outer and inner hair cell bundles in the organ of Corti. Analysis of the genomic DNA from deaf mice showed that in 13 cases, these mice had the Cre construct inserted into the first intron of the Sorcs2 gene, but in 21 cases, the insertion had occured in an Ig kappa locus (PubMed:28346477).|||N-glycosylated.|||Perikaryon|||Postsynaptic density membrane|||Proteolytic cleavage removes a propeptide, giving rise to a 122 kDa chain that includes a cytoplasmic tail. Further cleavage gives rise to a 104 kDa chain that lacks the cytoplasmic tail, and a membrane-bound 18 kDa chain (PubMed:24908487). The 104 kDa chain remains bound to the 18 kDa chain (By similarity).|||Recycling endosome membrane|||SORCS2 expression is decreased after the onset of symptoms in mouse models for Huntington disease (HD). SORCS2 does not interact with wild-type HTT, but does interact with mutant HTT containing a long polyglutamine stretch.|||Synapse|||The heterodimer formed by NGFR and SORCS2 functions as receptor for the precursor forms of NGF (proNGF) and BDNF (proBDNF) (PubMed:22155786, PubMed:24908487, PubMed:27457814, PubMed:29909994). ProNGF and proBDNF binding both promote axon growth cone collapse (in vitro) (PubMed:24908487). Plays a role in the regulation of dendritic spine density in hippocampus neurons (PubMed:29909994). Required for normal neurite branching and extension in response to BDNF (PubMed:27457814, PubMed:29909994). Plays a role in BDNF-dependent hippocampal synaptic plasticity (PubMed:29909994, PubMed:27457814). Together with NGFR and NTRK2, is required both for BDNF-mediated synaptic long-term depression and long-term potentiation (PubMed:27457814). ProNGF binding promotes dissociation of TRIO from the heterodimer, which leads to inactivation of RAC1 and/or RAC2 and subsequent reorganization of the actin cytoskeleton (By similarity). Together with the retromer complex subunit VPS35, required for normal expression of GRIN2A at synapses and dendritic cell membranes (PubMed:28469074). Required for normal expression of the amino acid transporter SLC1A1 at the cell membrane, and thereby contributes to protect cells against oxidative stress (PubMed:30840898).|||dendrite|||dendritic spine|||synaptosome http://togogenome.org/gene/10090:Spc25 ^@ http://purl.uniprot.org/uniprot/Q3UA16 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules.|||Belongs to the SPC25 family.|||Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end (By similarity).|||Nucleus|||kinetochore http://togogenome.org/gene/10090:Chrna5 ^@ http://purl.uniprot.org/uniprot/Q2MKA5|||http://purl.uniprot.org/uniprot/Q8BIE9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-5/CHRNA5 sub-subfamily.|||Cell membrane|||Membrane|||Neuronal AChR seems to be composed of two different types of subunits: alpha and non-alpha (beta). Interacts with LYPD6.|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Cpxm1 ^@ http://purl.uniprot.org/uniprot/Q3V190|||http://purl.uniprot.org/uniprot/Q9Z100 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||First expressed at 13.5 dpc, in the meninges, nasal mesenchyme, primordial cartilage and skeletal structures.|||May be involved in cell-cell interactions. No carboxypeptidase activity was found yet.|||Secreted|||Strongly expressed in testis and spleen. Moderately expressed in salivary gland, brain, heart, lung, and kidney. Extremely low expression in liver and muscle. No expression in eye, adrenal, and white adipose tissues. http://togogenome.org/gene/10090:Rgs19 ^@ http://purl.uniprot.org/uniprot/Q9CX84 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Fatty acylated. Heavily palmitoylated in the cysteine string motif (By similarity).|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G-alpha subfamily 1 members, with the order G(i)a3 > G(i)a1 > G(o)a >> G(z)a/G(i)a2. Activity on G(z)-alpha is inhibited by phosphorylation and palmitoylation of the G-protein (By similarity).|||Interacts with GIPC PDZ domain. Interacts with GNAO1.|||Membrane|||Phosphorylated, mainly on serine residues. http://togogenome.org/gene/10090:Zscan4d ^@ http://purl.uniprot.org/uniprot/A7KBS4 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Highly expressed at the 2-cell stage but its expression is rapidly turned off.|||Nucleus|||Transcription factor required to regulate early development. Binds telomeres and plays a key role in genomic stability by regulating telomere elongation. Acts as an activator of spontaneous telomere sister chromatid exchange (T-SCE) and telomere elongation (By similarity).|||telomere http://togogenome.org/gene/10090:Prrt3 ^@ http://purl.uniprot.org/uniprot/Q6PE13 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fam83e ^@ http://purl.uniprot.org/uniprot/Q80XS7 ^@ Function|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the FAM83 family.|||May interact with RAF1.|||May play a role in MAPK signaling.|||Probable cloning artifact. http://togogenome.org/gene/10090:Serf2 ^@ http://purl.uniprot.org/uniprot/A2ARQ4|||http://purl.uniprot.org/uniprot/P84102 ^@ Function|||Similarity ^@ Belongs to the SERF family.|||Positive regulator of amyloid protein aggregation and proteotoxicity (By similarity). Induces conformational changes in amyloid proteins, such as HTT, driving them into compact formations preceding the formation of aggregates (By similarity). http://togogenome.org/gene/10090:Nek11 ^@ http://purl.uniprot.org/uniprot/Q8C0Q4 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autorepressed by intramolecular binding of the C-terminus which dissociates following phosphorylation by NEK2. Activated in response to DNA damage. Inhibited by zinc.|||Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Interacts with NEK2.|||Nucleus|||Phosphorylated by NEK2. Phosphorylation at Ser-274 is important for its activation.|||Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation.|||nucleolus http://togogenome.org/gene/10090:Nemf ^@ http://purl.uniprot.org/uniprot/Q8CCP0 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NEMF family.|||Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit (By similarity). The complex probably also contains VCP/p97 and its ubiquitin-binding cofactors (By similarity). Interacts (via its N-terminus) with XPO1 (By similarity).|||Due to intron retention.|||Intron retention.|||Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degradation (PubMed:33406423). Thereby, frees 60S subunit ribosomes from the stalled translation complex and prevents the accumulation of nascent polypeptide chains that are potentially toxic for the cell (PubMed:33406423). Within the RQC complex, NEMF specifically binds stalled 60S ribosomal subunits by recognizing an exposed, nascent chain-conjugated tRNA moiety and promotes the recruitment of LTN1 to stalled 60S subunits (By similarity). Following binding to stalled 60S ribosomal subunits, NEMF mediates CAT tailing by recruiting alanine-charged tRNA to the A-site and directing the elongation of stalled nascent chains independently of mRNA or 40S subunits, leading to non-templated C-terminal alanine extensions (CAT tails) (PubMed:33406423). Mainly recruits alanine-charged tRNAs, but can also other amino acid-charged tRNAs (By similarity). CAT tailing is required to promote ubiquitination of stalled nascent chains by different E3 ubiquitin-protein ligases (By similarity). In the canonical RQC pathway (RQC-L), CAT tailing facilitates LTN1-dependent ubiquitination by exposing lysine residues that would otherwise remain buried in the ribosomal exit tunnel (By similarity). In the alternative RQC pathway (RQC-C) CAT tailing creates an C-degron mainly composed of alanine that is recognized by the CRL2(KLHDC10) and RCHY1/PIRH2 E3 ligases, leading to ubiquitination and degradation of stalled nascent chains (By similarity). NEMF may also indirectly play a role in nuclear export (By similarity).|||Nucleus|||cytosol http://togogenome.org/gene/10090:Asgr1 ^@ http://purl.uniprot.org/uniprot/P34927 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium is required for ligand binding.|||Expressed exclusively in hepatic parenchymal cells.|||Interacts with LASS2.|||Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.|||Membrane|||Phosphorylated on a cytoplasmic Ser residue. http://togogenome.org/gene/10090:Atp8a1 ^@ http://purl.uniprot.org/uniprot/A0A0M3HEP7|||http://purl.uniprot.org/uniprot/P70704|||http://purl.uniprot.org/uniprot/Q3U9N5|||http://purl.uniprot.org/uniprot/Q52KQ7|||http://purl.uniprot.org/uniprot/Q8CA15 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATPase activity is stimulated by phosphatidylserine (PS) and minimally by phosphatidylethanolamine (PE) (PubMed:16618126, PubMed:20224745). ATPase activity is inhibited by the vanadate and by the presence of calcium (PubMed:20224745).|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:20224745, PubMed:16618126). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. In vitro, its ATPase activity is selectively and stereospecifically stimulated by phosphatidylserine (PS) (PubMed:20224745, PubMed:16618126). The flippase complex ATP8A1:TMEM30A seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the cell membrane (PubMed:23269685). Acts as aminophospholipid translocase at the cell membrane in neuronal cells; the activity is associated with hippocampus-dependent learning (PubMed:22007859). May play a role in brain connectivity (PubMed:27287255).|||Cell membrane|||Cleaved by calpain in a caspase- and calcium influx-dependent manner only during platelet apoptosis and may lead to inactivation.|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit (PubMed:23269685). Interacts with TMEM30A to form a flippase complex; this complex forms an intermediate phosphoenzyme (PubMed:23269685). Interacts with TMEM30B; this interaction is reported conflictingly (By similarity).|||Cytoplasmic granule|||Cytoplasmic vesicle|||Endomembrane system|||Endoplasmic reticulum|||Found in most tissues except liver and testis. Most abundant in brain and lung. Also detected in fetal tissues. Isoform 1 is expressed in brain. Isoform 2 and isoform 3 are expressed in reticulocytes (PubMed:16643453). Expressed in mouse hippocampus in both dentate gyrus (DG) and the CA3 regions. Expressed in both neuronal as well as non-neuronal cells within the DG (PubMed:27287255). Highly expressed in platelets (PubMed:30674456).|||Golgi apparatus|||Initial characterization studies with purified Atp8a1 enzyme demonstrated similar but distinct properties compared to the cell membrane aminophospholipid flippase; however, the flippase complex accessory beta subunit was not included in the assays.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mice overexpressing ATP8A1 in brain display an autistic-like behavior but no difference in hippocampus-dependent learning. Unlike the mice overexpressing ATP8A1,homozygous knockout mice for ATP8A1 do not show any deficits in sociability behavior.|||chromaffin granule membrane http://togogenome.org/gene/10090:Or4g17 ^@ http://purl.uniprot.org/uniprot/Q8VF29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4c111 ^@ http://purl.uniprot.org/uniprot/Q7TR05 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptpn4 ^@ http://purl.uniprot.org/uniprot/Q9WU22 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cell membrane|||Highly expressed in testis. Specifically expressed in spermatocytes and spermatids within seminiferous tubules (at protein level).|||PTPN4-deficient mice are born at normal Mendelian ratio with no apparent developmental or phenotypic defects. They display normal cytokine production and T-cell effector functions (PubMed:18614237). However, they show impairment in motor learning and cerebellar long-term depression (PubMed:17953619).|||Phosphatase that plays a role in immunity, learning, synaptic plasticity or cell homeostasis (PubMed:17953619, PubMed:25825441). Regulates neuronal cell homeostasis by protecting neurons against apoptosis (By similarity). Negatively regulates TLR4-induced interferon beta production by dephosphorylating adapter TICAM2 and inhibiting subsequent TRAM-TRIF interaction (PubMed:25825441). Dephosphorylates also the immunoreceptor tyrosine-based activation motifs/ITAMs of the TCR zeta subunit and thereby negatively regulates TCR-mediated signaling pathway (PubMed:18614237). May act at junctions between the membrane and the cytoskeleton.|||cytoskeleton http://togogenome.org/gene/10090:Lrrc26 ^@ http://purl.uniprot.org/uniprot/Q91W20 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Required for the conversion of BK alpha channels from a high-voltage to a low-voltage activated channel type in non-excitable cells. These are characterized by negative membrane voltages and constant low levels of calcium (By similarity).|||Cell membrane|||Interacts with KCNMA1.|||The transmembrane domain is necessary for interaction with KCNMA1.|||cytoskeleton http://togogenome.org/gene/10090:Prr5l ^@ http://purl.uniprot.org/uniprot/A2AVJ5 ^@ Function|||PTM|||Similarity|||Subunit ^@ Associates with the mTORC2 complex that regulates cellular processes including survival and organization of the cytoskeleton (By similarity). Regulates the activity of the mTORC2 complex in a substrate-specific manner preventing for instance the specific phosphorylation of PKCs and thereby controlling cell migration (PubMed:22609986). Plays a role in the stimulation of ZFP36-mediated mRNA decay of several ZFP36-associated mRNAs, such as TNF-alpha and GM-CSF, in response to stress. Required for ZFP36 localization to cytoplasmic stress granule (SG) and P-body (PB) in response to stress.|||Belongs to the PROTOR family.|||Interacts with the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Interacts with RFFL. Interacts (via C-terminus) with ZFP36 (via C-terminus); this interaction may accelerate ZFP36-mediated mRNA decay during stress. Interacts with RICTOR.|||Ubiquitinated. Ubiquitination by RFFL promotes proteasomal degradation of PRR5L thereby modifying the substrate-specific activity of the mTORC2 complex. Ubiquitination by RFFL is stimulated by LPA/lysophosphatidic acid (By similarity). http://togogenome.org/gene/10090:Mybph ^@ http://purl.uniprot.org/uniprot/P70402 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. MyBP family.|||Binds to myosin; probably involved in interaction with thick myofilaments in the A-band.|||Skeletal muscle. Expressed at low levels in heart ventricles. http://togogenome.org/gene/10090:Ugt2a3 ^@ http://purl.uniprot.org/uniprot/Q8BWQ1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||Highly expressed in liver, with lower levels in duodenum and jejunum.|||Membrane|||UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity). http://togogenome.org/gene/10090:Gm20859 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Ddah2 ^@ http://purl.uniprot.org/uniprot/O08972|||http://purl.uniprot.org/uniprot/Q99LD8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DDAH family.|||Cytoplasm|||Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.|||Mitochondrion http://togogenome.org/gene/10090:Rabl6 ^@ http://purl.uniprot.org/uniprot/Q5U3K5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasm|||May enhance cellular proliferation. May reduce growth inhibitory activity of CDKN2A (By similarity).|||Nucleus http://togogenome.org/gene/10090:Clpsl2 ^@ http://purl.uniprot.org/uniprot/Q3UW21 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the colipase family.|||Secreted http://togogenome.org/gene/10090:Bche ^@ http://purl.uniprot.org/uniprot/Q03311 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.|||Homotetramer; disulfide-linked. Dimer of dimers (By similarity).|||No visible phenotype; due to the presence of other cholinesterases. Hypersensitive to acetylcholinesterase inhibitors, such as huperzine and donepezil. Treatment with the acetylcholinesterase inhibitor donepezil causes convulsions and death within 3 hours of dosing.|||Present in most cells except erythrocytes.|||Secreted http://togogenome.org/gene/10090:Myh1 ^@ http://purl.uniprot.org/uniprot/Q5SX40 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).|||Muscle contraction.|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||Represents a conventional myosin. This protein should not be confused with the unconventional myosin-1 (MYO1).|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||myofibril http://togogenome.org/gene/10090:Ap3d1 ^@ http://purl.uniprot.org/uniprot/O54774 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (By similarity). AP-3 associates with the BLOC-1 complex. Interacts with SLC30A2. Interacts with CLN3 (via dileucine motif); this interaction facilitates lysosomal targeting (By similarity).|||Belongs to the adaptor complexes large subunit family.|||Cytoplasm|||Golgi apparatus membrane|||Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes (By similarity). Involved in process of CD8+ T-cell and NK cell degranulation (By similarity). In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals (PubMed:21998198). http://togogenome.org/gene/10090:Lias ^@ http://purl.uniprot.org/uniprot/A0A0M3HEP3|||http://purl.uniprot.org/uniprot/Q99M04 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the radical SAM superfamily. Lipoyl synthase family.|||Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives.|||Expressed predominantly in heart, testis, and liver.|||Mitochondrion http://togogenome.org/gene/10090:Tjp3 ^@ http://purl.uniprot.org/uniprot/Q3UZ47|||http://purl.uniprot.org/uniprot/Q921G9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Ttf2 ^@ http://purl.uniprot.org/uniprot/Q5NC05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Cytoplasm|||DsDNA-dependent ATPase which acts as a transcription termination factor by coupling ATP hydrolysis with removal of RNA polymerase II from the DNA template. May contribute to mitotic transcription repression. May also be involved in pre-mRNA splicing (By similarity).|||Interacts with CDC5L. Part of the spliceosome (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gbp2 ^@ http://purl.uniprot.org/uniprot/Q9Z0E6 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||By IFNG/IFN-gamma and IFNB1/IFN-beta (PubMed:9862701, PubMed:18025219). Up-regulated upon infection by T.gondii or L.monocytogenes (PubMed:18025219). By IRF1 in response to bacterial infection (PubMed:25774715).|||Cytoplasm|||Cytoplasmic vesicle membrane|||Golgi apparatus membrane|||Homodimer; homodimerization occurs upon GTP-binding and is required for the association with membranous structures (By similarity). Heterodimer with other family members, including GBP1, GBP3, GBP4 and GBP5 (By similarity).|||Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:18025219, PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716, PubMed:27693356, PubMed:30062052). Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions, but the major reaction product is GDP (By similarity). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis, such as Gm12250/Irgb10: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (PubMed:24739961, PubMed:24715728, PubMed:25774715, PubMed:25774716, PubMed:27693356, PubMed:30062052). Confers protection to the protozoan pathogen Toxoplasma gondii (PubMed:18025219). Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity by inhibiting FURIN-mediated maturation of viral envelope proteins (By similarity).|||Isoprenylation is required for proper subcellular location.|||perinuclear region http://togogenome.org/gene/10090:Atp6v0a1 ^@ http://purl.uniprot.org/uniprot/Q3TXT5|||http://purl.uniprot.org/uniprot/Q3TY98|||http://purl.uniprot.org/uniprot/Q9Z1G4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase 116 kDa subunit family.|||Embryonic lethal. Knockout embryos die at 5 to 6 dpc, before gastrulation.|||Essential component of the vacuolar proton pump (V-ATPase), a multimeric enzyme that catalyzes the translocation of protons across the membranes. Required for assembly and activity of the V-ATPase.|||Melanosome|||Membrane|||Predominantly expressed in neurons in the cortex and in the dentate gyrus, CA1 and CA3 regions of the hippocampus (at protein level) (PubMed:33833240). Expressed at lower levels in astrocytes, oligodendrocytes and microglia (at protein level) (PubMed:33833240). In the cerebellum, present in Purkinje and granule cells (at protein level) (PubMed:33833240).|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for the acidification of various organelles, such as lysosomes, endosomes, the trans-Golgi network, and secretory granules, including synaptic vesicles. In certain cell types, can be exported to the plasma membrane, where it is involved in the acidification of the extracellular environment (By similarity). Required for assembly and activity of the vacuolar ATPase (By similarity). Through its action on compartment acidification, plays an essential role in neuronal development in terms of integrity and connectivity of neurons (PubMed:33833240).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with SPAAR (PubMed:28024296).|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Strn3 ^@ http://purl.uniprot.org/uniprot/B2RQS1|||http://purl.uniprot.org/uniprot/Q9ERG2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat striatin family.|||Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein (By similarity).|||Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein.|||Cytoplasm|||Interacts with protein phosphatase 2A (PP2A). Interacts with CDC42BPB.|||Mainly expressed in the brain and muscles but is also detected at low levels in various tissues such as kidney, spleen and lung.|||Membrane http://togogenome.org/gene/10090:Sgms2 ^@ http://purl.uniprot.org/uniprot/Q9D4B1 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sphingomyelin synthase family.|||Cell membrane|||Golgi apparatus membrane|||Highest expression is detected in cortical bone, followed by vertebrae, kidney and liver. Expression levels are very low in spleen, muscle, heart, brown fat and thymus (PubMed:30779713). Expressed in macrophages.|||Null mice are viable but exhibit increased cell membrane ceramide and decreased sphingomyelin levels. In both skeletal muscle and adipose tissue, there is a significant increase in glucose uptake. This leads to increased insulin sensitivity and ameliorated high-fat diet-induced obesity. There is blunted NFKB1- and MAP kinase-mediated responses to inflammatory stimuli and macrophages display increased cholesterol efflux into blood circulation. Liver SMS activity is markedly reduced (by about 80%) but only small change in macrophage SMS2 activity (16%). No change in glycosphingolipid levels in plasma. Atherosclerosis in SMS2(-/-)/LDLR(-/-) mice is significantly decreased.|||Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization.|||Sphingomyelin synthase that primarily contributes to sphingomyelin synthesis and homeostasis at the plasma membrane (PubMed:19590047, PubMed:21844222, PubMed:22580896). Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER. The direction of the reaction appears to depend on the levels of CER and DAG in the plasma membrane. Does not use free phosphorylcholine or CDP-choline as donors (By similarity). Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to ceramide (CER) to form ceramide phosphoethanolamine (CPE) (By similarity). Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:19590047, PubMed:21844222). To a lesser extent, plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1. Required for normal bone matrix mineralization (By similarity). http://togogenome.org/gene/10090:Washc2 ^@ http://purl.uniprot.org/uniprot/Q6PGL7 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC and retriever complexes subunits COMMD1 and CCDC93 as well as the retrievere complex subunit VPS35L.|||Belongs to the FAM21 family.|||Cell membrane|||Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5; in the complex interacts (via N-terminus) directly with WASHC1. The WASH core complex associates with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex. Interacts with VPS35; mediates the association with the retromer CSC complex. Interacts with FKBP15. Interacts with CCDC93, CCDC22, VPS35L; indicative for an association of the WASH core complex with the CCC and retriever complexes (By similarity). Directly interacts with TBC1D23 (PubMed:29084197).|||Contaminating sequence. Potential poly-A sequence.|||Early endosome membrane|||The LFa (leucine-phenylalanine-acidic) motif bind directly to VPS35 of retromer CSC; adjacent motifs can act cooperatively to bind multiple CSCs, although there is significant variability in the affinities of different motifs for retromer. http://togogenome.org/gene/10090:Fxyd7 ^@ http://purl.uniprot.org/uniprot/P59648 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FXYD family.|||Membrane http://togogenome.org/gene/10090:Pam16 ^@ http://purl.uniprot.org/uniprot/Q9CQV1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TIM16/PAM16 family.|||Expressed in trabecular bone and cartilage and by differentiated chondrocytes localized in the hypertrophic zone and by osteoblasts at early developmental stages.|||Mitochondrion inner membrane|||Probable component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19 (By similarity). Interacts with DNAJC19. Directly interacts with DNAJC15; this interaction counteracts DNAJC15-dependent stimulation of HSPA9 ATPase activity (By similarity). Associates with the TIM23 complex (Probable).|||Regulates ATP-dependent protein translocation into the mitochondrial matrix. Inhibits DNAJC19 stimulation of HSPA9/Mortalin ATPase activity.|||The J-like region, although related to the J domain does not have co-chaperone activity. http://togogenome.org/gene/10090:Or5d36 ^@ http://purl.uniprot.org/uniprot/Q8VFR4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc25a17 ^@ http://purl.uniprot.org/uniprot/O70579 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Cytoplasm|||Expressed in liver, kidney, heart, spleen, muscle and lung.|||Interacts (via N- and C-terminus peroxisomal targeting regions) with PEX19; the interaction occurs with the newly synthesized SLC25A17 in the cytosol.|||Peroxisomal transporter for multiple cofactors like coenzyme A (CoA), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and nucleotide adenosine monophosphate (AMP), and to a lesser extent for nicotinamide adenine dinucleotide (NAD(+)), adenosine diphosphate (ADP) and adenosine 3',5'-diphosphate (PAP). May catalyze the transport of free CoA, FAD and NAD(+) from the cytosol into the peroxisomal matrix by a counter-exchange mechanism.|||Peroxisome membrane|||The N- and C-terminal portions are exposed to the cytoplasm. Lacks a typical peroxisomal sorting signal. A region between helical transmembrane domains (TM) 4 and 5 and TM1-TM3 or TM4-TM6 are necessary for the peroxisome-targeting activity. http://togogenome.org/gene/10090:Dnajc4 ^@ http://purl.uniprot.org/uniprot/Q9D844 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dusp9 ^@ http://purl.uniprot.org/uniprot/Q7TNL7 ^@ Similarity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily. http://togogenome.org/gene/10090:Dok7 ^@ http://purl.uniprot.org/uniprot/Q18PE0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Expressed in the central region encompassing the endplate area of the diaphragm muscles at day 14.5 of embryonic development (14.5 dpc), when AChRs cluster in a nerve- and agrin-independent manner.|||Homodimer. Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via IRS-type PTB domain) with MUSK (via cytoplasmic part); requires MUSK phosphorylation.|||Mice are immobile at birth and die shortly thereafter. They do not form neither acetylcholine receptor clusters nor neuromuscular synapses.|||Probable muscle-intrinsic activator of MUSK that plays an essential role in neuromuscular synaptogenesis. Acts in aneural activation of MUSK and subsequent acetylcholine receptor (AchR) clustering in myotubes. Induces autophosphorylation of MUSK.|||Synapse|||The PH domain mediated binding to phospholipids with phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate. http://togogenome.org/gene/10090:Ccdc42 ^@ http://purl.uniprot.org/uniprot/Q5SV66 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the CFAP73 family.|||Mice develop normally without obvious somatic defects but males are sterile due to malformation of the sperm flagella. Sperm cells display defects in the number and location of the head-tail coupling apparatus and lack flagellated sperm.|||Only expressed in the brain and developing sperm. Expression in the testes appears at approximately ten days of age and is maintained into adulthood, corresponding with the onset of meiosis. Expression in the testes appears limited to adluminal spermatids that are engaged in the assembly of flagella. Strong expression is observed in the spermatids within the lumen of the seminiferous tubules in testes from 8-week-old mice, but not in cells adjacent to the basement membrane of the tubule, including Sertoli cells, spermatogonia and spermatocytes. Not expressed in ovaries.|||Required for sperm development. http://togogenome.org/gene/10090:Gm10486 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Bdp1 ^@ http://purl.uniprot.org/uniprot/Q571C7 ^@ Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of TFIIIB complex. The TFIIIB complex has two activities, alpha and beta. The TFIIIB-alpha and TFIIIB-beta activities are required for transcription of genes with TFIIIC-bound internal promoters and PSE transcription factor-bound external promoters, respectively. The TFIIIB-alpha activity complex is composed of TBP, BDP1, and a complex containing both BRF2 and at least four stably associated proteins; YY1 facilitates the formation of TFIIIB-alpha activity complex. The TFIIIB-beta activity complex is composed of TBP, BDP1, and BRF1. Interacts with BRF1; this interaction diminishes during mitosis resulting in the release of BDP1 from chromosomal templates. Component of TFIIIC complex. The TFIIIC complex has two activities, C1 and C2. The TFIIIC2 activity complex is only required for transcription of the 'classical' pol III genes whereas the TFIIIC1 activity complex is required for transcription of all pol III genes. The TFIIIC1 activity complex is composed at least of BDP1. Interacts with ZBTB43 (By similarity).|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Expressed in the cochlea, particularly in the spiral ligament, the capillaries of the stria vascularis and the basilar membrane.|||General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site (By similarity).|||Nucleus|||Phosphorylated by CSNK2A1 during mitosis, resulting in its release from chromatin and suppression of polymerase III transcription. http://togogenome.org/gene/10090:Ftl1 ^@ http://purl.uniprot.org/uniprot/Q9CPX4 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Lrrc4b ^@ http://purl.uniprot.org/uniprot/P0C192 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with PTPRF (By similarity). Interacts with DLG4.|||Membrane|||N-glycosylated. O-glycosylated; contains sialic acid.|||Presynaptic cell membrane|||Synaptic adhesion protein. Regulates the formation of excitatory synapses. The trans-synaptic adhesion between LRRC4B and PTPRF regulates the formation of excitatory synapses in a bidirectional manner (By similarity).|||The extreme C-terminus binds to the first 2 PDZ domains of DLG4. http://togogenome.org/gene/10090:Cd244a ^@ http://purl.uniprot.org/uniprot/Q07763 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in natural killer (NK) cells, T cells and dendritic cells.|||Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor (PubMed:8326140, PubMed:12734329, PubMed:19648922, PubMed:20962259). Activating function implicates association with SH2D1A and FYN. Downstreaming signaling involves predominantly VAV1, and, to a lesser degree, INPP5D/SHIP1 and CBL. Signal attenuation in the absence of SH2D1A is proposed to be dependent on INPP5D and to a lesser extent PTPN6/SHP-1 and PTPN11/SHP-2. Stimulates NK cell cytotoxicity, production of IFN-gamma and granule exocytosis (PubMed:8326140, PubMed:15169881, PubMed:15998796, PubMed:22683124). Optimal expansion and activation of NK cells seems to be dependent on the engagement of CD244 with CD48 expressed on neighboring NK cells (PubMed:15905190). Regulation of NK cell activity by adapters Sh2d1b and Sh2d1b2 is reported conflictingly (PubMed:16127454, PubMed:16425036). Acts as costimulator in NK activation by enhancing signals by other NK receptors such as NCR3 and NCR1. At early stages of NK cell differentiation may function as an inhibitory receptor possibly ensuring the self-tolerance of developing NK cells (By similarity). Involved in the regulation of CD8(+) T-cell proliferation; expression on activated T-cells and binding to CD48 provides costimulatory-like function for neighboring T-cells (PubMed:11739483). Inhibits inflammatory responses in dendritic cells (DCs) (PubMed:25643613).|||Interacts with CD48 (PubMed:9841922, PubMed:15905190). Interacts (via phosphorylated ITSM 1-4) with SH2D1A/SAP (via SH2 domain); SH2D1A probably mediates association with FYN. Interacts (via phosphorylated ITSM 3) with PTPN11/SHP-2, INPP5D/SHIP1, PTPN6/SHP-1 and CSK; binding of SH2D1A prevents association with PTPN11, PTPN6 and CSK. Interacts weakly (via phosphorylated ITSM 2) with PTPN11 and CSK. Interacts with SH2D1B and SH2D1B2. Interacts with MHC class I proteins; the interaction is proposed to prevent self-killing of NK cells (By similarity).|||Membrane|||N-linked glycosylation is essential for the binding to its ligand CD48. Also O-glycosylated, in contrast, O-linked sialylation has a negative impact on ligand binding (By similarity).|||Phosphorylated by FYN and CSK at tyrosine residues following activation. Coligation with inhibitory receptors such as KIR2DL1 inhibits phosphorylation upon contact of NK cells with sensitive target cells.|||The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). http://togogenome.org/gene/10090:Tbr1 ^@ http://purl.uniprot.org/uniprot/Q64336 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the developing and adult cortex (PubMed:11239428). Expressed in the olfactory bulbs (PubMed:9883721).|||First detected around day 10 of embryonic development in the preplate, at day 12.5, in the cortical plate and intermediate zone, and from day 16.5 to 18.5, in a rostro-caudal gradient in the subplate. In the thalamus, expression is first observed at postnatal stage, P7, and weak expression continues in later postnatal and adult stages.|||Homodimer (By similarity). Part of a complex containing CASK, TBR1 and TSPYL2; may modulate gene expression in response to neuronal synaptic activity (PubMed:15066269). Forms homodimers (By similarity). Interacts with FOXP2 (By similarity). Interacts with FOXP1 (By similarity). Interacts with BCL11A (By similarity).|||Homozygous mutant mice do not nurse and die between postnatal days 1 and 3 (PubMed:9883721, PubMed:11239428). Brains are smaller than those of heterozygous or wild-type littermates, olfactory bulbs are small and olfactory bulb projection neurons are absent (PubMed:9883721). Mutant mice show severe defects of cortical development (PubMed:11239428).|||Nucleus|||Transcriptional repressor involved in multiple aspects of cortical development, including neuronal migration, laminar and areal identity, and axonal projection (PubMed:9883721, PubMed:11239428, PubMed:21285371). As transcriptional repressor of FEZF2, it blocks the formation of the corticospinal (CS) tract from layer 6 projection neurons, thereby restricting the origin of CS axons specifically to layer 5 neurons (PubMed:21285371). http://togogenome.org/gene/10090:Chkb ^@ http://purl.uniprot.org/uniprot/O55229 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the choline/ethanolamine kinase family.|||Defects in Chkb are a cause of rostrocaudal muscular dystrophy (rmd). The disease is characterized by rapidly progressive muscular dystrophy and neonatal forelimb bone deformity. The dystrophy is only evident in skeletal muscle tissues in an unusual rostral-to-caudal gradient.|||Expressed ubiquitously with the highest level in testis.|||Has a key role in phospholipid metabolism, and catalyzes the first step of phosphatidylethanolamine and phosphatidylcholine biosynthesis.|||Hindlimb muscular dystrophy. Hindlimb skeletal muscle tissue exhibits impaired phosphatidylcholine biosynthesis and increased phosphatidylcholine catabolism, with concomitant accumulation of choline. Mitochondria are abnormally large and exhibit decreased inner membrane potential.|||Homodimer, and heterodimer with CHKA. http://togogenome.org/gene/10090:Naxd ^@ http://purl.uniprot.org/uniprot/J3QMM7|||http://purl.uniprot.org/uniprot/J3QN06|||http://purl.uniprot.org/uniprot/K3W4M4|||http://purl.uniprot.org/uniprot/Q9CZ42 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NnrD/CARKD family.|||Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mitochondrion http://togogenome.org/gene/10090:Tbx19 ^@ http://purl.uniprot.org/uniprot/Q99ME7 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Transcriptional regulator involved in developmental processes. Can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters. http://togogenome.org/gene/10090:Scgb2b10 ^@ http://purl.uniprot.org/uniprot/A0A089N5R6 ^@ Similarity ^@ Belongs to the secretoglobin family. http://togogenome.org/gene/10090:Oasl2 ^@ http://purl.uniprot.org/uniprot/Q9Z2F2 ^@ Activity Regulation|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the 2-5A synthase family.|||Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. Synthesizes oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L.|||Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators.|||Strongly expressed in spleen dendritic cells, whereas, in bone marrow-derived dendritic cells, the amount increases during the maturation process. Expressed in many organs, the highest levels being in thymus, lung, and bone marrow. http://togogenome.org/gene/10090:Dis3l2 ^@ http://purl.uniprot.org/uniprot/Q8CI75 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation.|||Belongs to the RNR ribonuclease family. DIS3L2 subfamily.|||Cytoplasm|||Interacts with XRN1.|||P-body|||Specifically recognizes and binds polyuridylated RNAs via 3 RNA-binding regions (named U-zone 1, U-zone 2 and U-zone 3) that form an open funnel on one face of the catalytic domain, allowing RNA to navigate a path to the active site. http://togogenome.org/gene/10090:Akap9 ^@ http://purl.uniprot.org/uniprot/E9QQ10|||http://purl.uniprot.org/uniprot/Q70FJ1 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Golgi apparatus|||Incomplete sequence.|||Interacts with the regulatory region of protein kinase N (PKN), protein phosphatase 2A (PP2A), protein phosphatase 1 (PP1) and the immature non-phosphorylated form of PKC epsilon. Interacts with CIP4 and FNBP1. Interacts with chloride intracellular channel proteins CLIC1, CLIC4 and CLIC5. CSNK1D binding promotes its centrosomal subcellular location. Interacts with GM130/GOLGA2; leading to recruitment to the Golgi apparatus. Interacts with KCNQ1; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1), to the heterodimer KCNQ1-KCNE1. Interacts with PDE4DIP isoform 2; this interaction stabilizes both proteins. In complex with PDE4DIP isoform 2, recruits CAMSAP2 to the Golgi apparatus. Forms a pericentrosomal complex with CDK5RAP2, EB1/MAPRE1 and PDE4DIP isoform 2; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP. Interacts with MAPRE1 and MAPRE3. Interacts (via C-terminus) with CAMSAP2; this interaction is much stronger in the presence of PDE4DIP isoform 2. Interacts with CAMSAP3. Interacts (via C-terminus) with the gamma-tubulin ring complex (gamma-TuRC), composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6.|||RII-binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.|||Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus. Required for microtubule nucleation at the cis-side of the Golgi apparatus. Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase. In complex with PDE4DIP isoform 2/MMG8/SMYLE, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. In complex with PDE4DIP isoform 2, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery.|||centrosome http://togogenome.org/gene/10090:Capn2 ^@ http://purl.uniprot.org/uniprot/O08529 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by 200-1000 micromolar concentrations of calcium and inhibited by calpastatin.|||Belongs to the peptidase C2 family.|||Binds 7 Ca(2+) ions.|||Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' (By similarity). Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs (PubMed:22711986).|||Cell membrane|||Cytoplasm|||Forms a heterodimer with a small (regulatory) subunit (CAPNS1) (By similarity). Interacts with CPEB3; this leads to cleavage of CPEB3 (PubMed:22711986).|||Ubiquitous. http://togogenome.org/gene/10090:Zfp90 ^@ http://purl.uniprot.org/uniprot/Q61967 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ After frameshift's correction, the CDS was not identified.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Brain, spleen, thymus, and testis (PubMed:7576184). Expressed in heart (PubMed:7576184, PubMed:21284946).|||Inhibits the transcriptional repressor activity of REST by inhibiting its binding to DNA, thereby derepressing transcription of REST target genes.|||Interacts (via N- and C-termini) with REST (via zinc-finger DNA-binding domain); the interaction inhibits REST repressor activity.|||Nucleus|||There is a marked increase after postnatal stages 18-20 (simultaneously to the appearance of haploid cell stages). Maximal expression is observed around 2 weeks postnatally, with the exception of brain and testis, where the expression is highest in earlier developmental stages. http://togogenome.org/gene/10090:Pak5 ^@ http://purl.uniprot.org/uniprot/Q8C015 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An autoinhibitory domain is present in the N-terminal region of the protein.|||Autophosphorylated when activated by CDC42/p21.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Expressed in fetal brain.|||Highly expressed in brain and eye. Also expressed in adrenal gland, pancreas, prostate and testes. Within the brain, expression is restricted to neurons. Present in brain but not in kidney, lung and spleen (at protein level).|||Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with MARK2, leading to inhibit MARK2 independently of kinase activity. Interacts with RHOD and RHOH (By similarity).|||Mice are viable and fertile, and show normal development of brain, eye, pancreas and adrenal gland.|||Mitochondrion|||Nucleus|||Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions (By similarity). http://togogenome.org/gene/10090:Defb25 ^@ http://purl.uniprot.org/uniprot/Q30KN8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Onecut3 ^@ http://purl.uniprot.org/uniprot/Q8K557 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CUT homeobox family.|||Expressed in the endoderm from the 14-somite stage. Aroound 9.5 dpc, present in the ventral prepancreatic and prehepatic regions (at protein level). At 14.5 dpc, expressed in brain, stomach and gut.|||Nucleus|||Specifically expressed in brain, stomach and gut. Within the gut, expressed only in duodenum and jejunum.|||Transcriptional activator. Binds the consensus DNA sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR.|||Transcriptionally regulated by ONECUT1 in the developing endoderm. http://togogenome.org/gene/10090:Zdhhc16 ^@ http://purl.uniprot.org/uniprot/Q9ESG8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family.|||Endoplasmic reticulum membrane|||Interacts with ABL1 (PubMed:12021275). Interacts with COPS5 (By similarity).|||Lethality one day after birth (PubMed:26644582). Pups and embryos show eye malformation and heart defects (PubMed:26644582). Mice display cardiomyopathy and cardiac defects including bradycardia (PubMed:26644582). Heart defects are characterized by thinner and enlarged ventricular walls, cardiomyocyte disarray and abnormal nucleus morphology (PubMed:26644582).|||Palmitoyl acyltransferase that mediates palmitoylation of proteins such as PLN and ZDHHC6 (PubMed:26644582). Required during embryonic heart development and cardiac function, possibly by mediating palmitoylation of PLN, thereby affecting PLN phosphorylation and homooligomerization (PubMed:26644582). Also required for eye development (PubMed:26644582). Palmitoylates ZDHHC6, affecting the quaternary assembly of ZDHHC6, its localization, stability and function (By similarity). May play a role in DNA damage response (PubMed:27159997). May be involved in apoptosis regulation (PubMed:12021275). Involved in the proliferation of neural stem cells by regulating the FGF/ERK pathway (By similarity).|||Ubiquitously expressed. http://togogenome.org/gene/10090:Manba ^@ http://purl.uniprot.org/uniprot/A0A0R4J092|||http://purl.uniprot.org/uniprot/Q8K2I4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 2 family.|||Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.|||Highest level in liver, high levels in lung, testis, skin and spleen, moderate level in thymus. Activity found in plasma, kidney, liver, spleen, pancreas, brain, testis, epididymis, heart, lung and skeletal muscle.|||Lysosome|||Mice are born at the expected Mendelian rate and display no visible phenotype for at least one year. However, they display vacuolation in the central nervous system and accumulation of disaccharides in brain and epididymis, detectable already at four weeks after birth.|||Monomer. http://togogenome.org/gene/10090:Tmem37 ^@ http://purl.uniprot.org/uniprot/Q9JJV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Membrane|||The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma.|||Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity). Modulates calcium current when coexpressed with CACNA1G. http://togogenome.org/gene/10090:Mycs ^@ http://purl.uniprot.org/uniprot/Q9Z304 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Has apoptosis-inducing activity.|||Nucleus http://togogenome.org/gene/10090:Plekhm2 ^@ http://purl.uniprot.org/uniprot/Q80TQ5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with KLC2 (via TPR repeats). Interacts with KIF5B. Interacts with BORCS5. Interacts (via RUN domain) with ARL8B (GTP-bound form); PLEKHM1 and PLEKHM2 compete for interaction with ARL8B. Interacts with ARL8A.|||Lysosome membrane|||Plays a role in lysosomes movement and localization at the cell periphery acting as an effector of ARL8B. Required for ARL8B to exert its effects on lysosome location, recruits kinesin-1 to lysosomes and hence direct their movement toward microtubule plus ends. Binding to ARL8B provides a link from lysosomal membranes to plus-end-directed motility. Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells. Required for maintenance of the Golgi apparatus organization. May play a role in membrane tubulation. http://togogenome.org/gene/10090:Cltb ^@ http://purl.uniprot.org/uniprot/Q3TJ95|||http://purl.uniprot.org/uniprot/Q3TWZ9|||http://purl.uniprot.org/uniprot/Q6IRU5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the clathrin light chain family.|||Clathrin coats are formed from molecules containing 3 heavy chains and 3 light chains. Interacts (via N-terminus) with HIP1. Interacts with HIP1R.|||Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.|||Cytoplasmic vesicle membrane|||coated pit http://togogenome.org/gene/10090:Nelfa ^@ http://purl.uniprot.org/uniprot/Q8BG30 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NELF-A family.|||Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (By similarity). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (By similarity).|||Nucleus|||The HDAg-like domain is essential for transcriptional repression, and mediates the interaction with the RNA polymerase II complex.|||The NELF complex is composed of NELFA, NELFB, NELFCD and NELFE; NELFA and NELFCD form a stable subcomplex that binds to the N-terminus of NELFB (By similarity). In vitro, the NELFA:NELFCD subcomplex binds to ssDNA and ssRNA in a sequence- and structure-dependent manner (By similarity). Interacts with the RNA polymerase II complex when it is not phosphorylated by P-TEFb (By similarity). Interacts with NELFB (PubMed:26010750).|||Ubiquitous. Expressed in brain, heart, spleen, lung, liver, muscle, kidney and testis. Already expressed in 7 dpc embryos. http://togogenome.org/gene/10090:Or10h5 ^@ http://purl.uniprot.org/uniprot/K7N6V7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sprr1b ^@ http://purl.uniprot.org/uniprot/Q62267 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.|||Cytoplasm|||Expressed in fetal periderm, hair follicles and in the thickened epidermis of the lip and footpad. Also present in the epithelia of various tissues such as the penis, vagina, forestomach, tongue and esophagus.|||First detected in fetal skin around day 16 and expression continues throughout newborn and adult stages. http://togogenome.org/gene/10090:Tet2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JF55|||http://purl.uniprot.org/uniprot/Q4JK59 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TET family.|||Binds 1 Fe(2+) ion per subunit.|||Binds 3 zinc ions per subunit. The zinc ions have a structural role.|||Chromosome|||Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.|||Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming during embryonic development.|||Expressed at high levels in early embryos from 1-cell stage until at least blastula (PubMed:24357321). Expressed during embryonic development in both somatic and primordial germ cells from 9.5 dpc, with a peak in primordial germ cells at 16.5 dpc (PubMed:23151479).|||Expressed in the brain, kidney, heart, lung, muscle and stomach (PubMed:16722336, PubMed:24357321). Expressed in germinal vesicle (GV) stage and MII-stage oocytes and in early embryos (PubMed:24357321). Present in embryonic stem cells (ES cells) (PubMed:20639862).|||Interacts with HCFC1 (By similarity). Interacts with OGT (PubMed:23352454). Interacts with PROSER1; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2 (By similarity). Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex (By similarity).|||May be glycosylated. It is unclear whether interaction with OGT leads to GlcNAcylation. According to a report, it is GlcNAcylated by OGT (PubMed:23352454). In contrast, another group reports no GlcNAcylation by OGT in human ortholog.|||Mice are viable and fertile but develop chronic myelomonocytic leukemia probably caused by dysregulation of hematopoietic stem cells. Mice lacking both Tet1 and Tet2 are fertile, with females having smaller ovaries and reduced fertility. They display decreased 5-hydroxymethylcytosine (5hmC) and abnormal methylation at various imprinted loci. Embryonic stem cells lacking both Tet1 and Tet2 remain pluripotent but lack 5hmC, leading to developmental defects in chimeric embryos.|||Monoubiquitinated at Lys-1212 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.|||Nucleus|||Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG (PubMed:21817016).|||The zinc ions have a structural role. http://togogenome.org/gene/10090:Acsl6 ^@ http://purl.uniprot.org/uniprot/Q5F2D0|||http://purl.uniprot.org/uniprot/Q5ICG4|||http://purl.uniprot.org/uniprot/Q5ICG5|||http://purl.uniprot.org/uniprot/Q8R1X1|||http://purl.uniprot.org/uniprot/Q91WC3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (By similarity). Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid (By similarity).|||Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane|||Mitochondrion outer membrane|||Peroxisome membrane http://togogenome.org/gene/10090:Fnbp1 ^@ http://purl.uniprot.org/uniprot/A2AQ41|||http://purl.uniprot.org/uniprot/A2AQ43|||http://purl.uniprot.org/uniprot/A2AQ44|||http://purl.uniprot.org/uniprot/Q80TY0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FNBP1 family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Expressed in brain and testis.|||Homodimerizes, the dimers can polymerize end-to-end to form filamentous structures. Interacts specifically with GTP-bound RND2 and CDC42. Interacts with AKAP9, ARHGAP17, DAAM1, DIAPH1, DIAPH2, DNM1, DNM2, DNM3, FASLG/FASL, microtubules, PDE6G, SNX2 and WASL/N-WASP. May interact with TNKS (By similarity).|||Lysosome|||Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during the late stage of clathrin-mediated endocytosis. Binds to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promotes membrane invagination and the formation of tubules. Also enhances actin polymerization via the recruitment of WASL/N-WASP, which in turn activates the Arp2/3 complex. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. May act as a link between RND2 signaling and regulation of the actin cytoskeleton. May be required for the lysosomal retention of FASLG/FASL (By similarity).|||The F-BAR domain binds the phospholipid membrane with its concave surface. The end-to-end polymerization of dimers of these domains provides a curved surface that fits best membranes with around 600 A diameter, and may drive tubulation (By similarity).|||cell cortex|||clathrin-coated pit|||cytoskeleton http://togogenome.org/gene/10090:Nme1 ^@ http://purl.uniprot.org/uniprot/P15532|||http://purl.uniprot.org/uniprot/Q5NC81 ^@ Activity Regulation|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylation at His-118 increases serine/threonine protein kinase activity of the enzyme. Interaction with the SET complex inhibits exonuclease activity (By similarity).|||Belongs to the NDK family.|||Cytoplasm|||Hexamer of two different chains: A and B (A6, A5B, A4B2, A3B3, A2B4, AB5, B6). Interacts with PRUNE1. Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Within this complex, interacts directly with SET. Also interacts with TREX1, but only following translocation to the nucleus.|||Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. During GZMA-mediated cell death, works in concert with TREX1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (By similarity).|||Nucleus|||This protein is found in reduced amount in tumor cells of high metastatic potential. http://togogenome.org/gene/10090:Tas2r135 ^@ http://purl.uniprot.org/uniprot/B9EII2|||http://purl.uniprot.org/uniprot/Q7TQA9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Spen ^@ http://purl.uniprot.org/uniprot/A2ADB0|||http://purl.uniprot.org/uniprot/A2ADB1|||http://purl.uniprot.org/uniprot/Q62504 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM Spen family.|||Highly expressed in testis. Expressed at lower level in brain, lung, spleen, liver and kidney. Weakly expressed in cardiac and skeletal muscles and ovary. In spleen, it is expressed in follicular B-cells, while it is weakly expressed in marginal zone B-cells.|||Interacts with NCOR2, HDAC1, HDAC2, RBBP4, MBD3 and MTA1L1. Interacts with the nuclear receptors RAR and PPARD. Interacts with RAR in absence of ligand. Binds to the steroid receptor RNA coactivator SRA (By similarity). Interacts with MSX2. Interacts with RBPSUH; this interaction may prevent the interaction between RBPSUH and NOTCH1. Binds to HIPK3.|||May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways, such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.|||Nucleus|||The RID domain mediates the interaction with nuclear receptors.|||The SPOC domain, which mediates the interaction with NCOR2, is essential for the repressive activity. http://togogenome.org/gene/10090:F2rl3 ^@ http://purl.uniprot.org/uniprot/O88634 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Highly expressed in the spleen. Slight expression in the heart, lung, skeletal muscle and kidney. No detectable expression in brain, liver or testis. Also detected in platelets.|||Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation. http://togogenome.org/gene/10090:Pycr2 ^@ http://purl.uniprot.org/uniprot/Q3TMZ1|||http://purl.uniprot.org/uniprot/Q922Q4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pyrroline-5-carboxylate reductase family.|||Cytoplasm|||Homodecamer; composed of 5 homodimers. Interacts with LTO1.|||Housekeeping enzyme that catalyzes the last step in proline biosynthesis. In some cell types, such as erythrocytes, its primary function may be the generation of NADP(+). Can utilize both NAD and NADP. Has higher affinity for NADP, but higher catalytic efficiency with NADH (By similarity). Involved in cellular response to oxidative stress (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Or7e166 ^@ http://purl.uniprot.org/uniprot/Q7TRF7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:AU015228 ^@ http://purl.uniprot.org/uniprot/Q3TQQ1 ^@ Similarity ^@ Belongs to the TFIIE alpha subunit family. http://togogenome.org/gene/10090:Defb18 ^@ http://purl.uniprot.org/uniprot/Q30KP5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Scn11a ^@ http://purl.uniprot.org/uniprot/Q9R053 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.9/SCN11A subfamily.|||Cell membrane|||Expressed in embryo at 15 dpc onwards.|||Expressed in the dorsal root ganglia (C-fiber neurons), spinal cord, trigeminal ganglia, testis, ovary, uterus and small intestine.|||Sodium channel mediating the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient (PubMed:24036948). Involved in membrane depolarization during action potential in nociceptors which function as key relay stations for the electrical transmission of pain signals from the periphery to the central nervous system (PubMed:24036948). Also involved in rapid BDNF-evoked neuronal depolarization (By similarity).|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.|||The voltage-resistant sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more auxiliary subunits SCN1B, SCN2B and SCN3B. http://togogenome.org/gene/10090:Fzd2 ^@ http://purl.uniprot.org/uniprot/Q9JIP6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Expressed in embryonic and adult heart, lung, chondrocytes and brain. Also expressed in the developing gastrointestinal tract (strongest in foregut), much weaker expression in the adult. No expression in fetal liver and adult spleen. Up-regulated in esophageal squamous cell carcinomas.|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (By similarity). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Gm21708 ^@ http://purl.uniprot.org/uniprot/O35698 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with splicing factor proteins SFRS3/SRP20, TRA2B/SFRS10, KHDRBS1/SAM68 and KHDRBS3.|||Nucleus|||Only expressed in spermatogonia and early spermatocytes, suggesting that expression is inactivated in the XY body during meiosis.|||Overexpression of Rbmy proteins in mice carrying the Y(d1) deletion that removes most of the multi-copy Rbmy gene cluster does not have any effect and fails to reduce the frequency of abnormal sperm. These results raize the question of the role of Rbmy proteins in sperm development.|||RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs.|||Testis-specific.|||The RBMY1 proteins are encoded by repeated regions of the Y chromosome. The exact number of functional copies is unclear and may vary between individuals, and some of them may represent pseudogenes. http://togogenome.org/gene/10090:Tac2 ^@ http://purl.uniprot.org/uniprot/P55099 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tachykinin family.|||Secreted|||Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles. Is a critical central regulator of gonadal function (By similarity). http://togogenome.org/gene/10090:Emc1 ^@ http://purl.uniprot.org/uniprot/Q8C7X2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC1 family.|||Component of the ER membrane protein complex (EMC).|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Ldlrad4 ^@ http://purl.uniprot.org/uniprot/Q4VAH9|||http://purl.uniprot.org/uniprot/Q8BWJ4 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMEPA1 family.|||Detected in all tissues tested.|||Early endosome membrane|||Endosome membrane|||Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal.|||Interacts with PMEPA1. Interacts (via the SMAD interaction motif) with SMAD2 and SMAD3 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||The SMAD interaction motif is required for interaction with SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling. http://togogenome.org/gene/10090:Strip2 ^@ http://purl.uniprot.org/uniprot/B2RW20|||http://purl.uniprot.org/uniprot/Q8C9H6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STRIP family.|||Component of striatin-interacting phosphatase and kinase (STRIPAK) complex. Interacts with CTTNBP2NL (By similarity).|||Cytoplasm|||Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (By similarity). http://togogenome.org/gene/10090:Pom121 ^@ http://purl.uniprot.org/uniprot/Q8K3Z9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the POM121 family.|||Contains F-X-F-G repeats.|||Endoplasmic reticulum membrane|||Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL) (By similarity).|||Nucleus membrane|||Proteolytically cleaved by caspase-3 during apoptosis.|||nuclear pore complex http://togogenome.org/gene/10090:Galntl6 ^@ http://purl.uniprot.org/uniprot/E5D8G1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Msr1 ^@ http://purl.uniprot.org/uniprot/P30204 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homotrimer (PubMed:8394868). Interacts with MYO18A (By similarity).|||Membrane|||Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL). http://togogenome.org/gene/10090:Irf7 ^@ http://purl.uniprot.org/uniprot/D3Z4U9|||http://purl.uniprot.org/uniprot/P70434|||http://purl.uniprot.org/uniprot/Q3TW14|||http://purl.uniprot.org/uniprot/Q542T3 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Lys-63'-linked ubiquitination by NEURL3 promotes IRF7 activation.|||Acetylation inhibits its DNA-binding ability and activity.|||Belongs to the IRF family.|||Cytoplasm|||In response to a viral infection, phosphorylated by TBK1 and IKBKE1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling pathway, phosphorylated by IRAK1 (By similarity).|||In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes.|||Induced by lipopolysaccharide (LPS) (PubMed:27129230). Induced by type I interferon (IFN) and viruses (HIV-1 and SeV viruses) (PubMed:27129230).|||Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:27129230, PubMed:22095711). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner (PubMed:27129230). Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages.|||Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3. Interacts with TICAM1 and TICAM2. Interacts with MYD88 and TRAF6. Interacts with NMI; the interaction is direct and leads to the inhibition of IRF7-mediated type I IFN production (PubMed:23956435). Interacts with GBP4; preventing interaction between TRAF6 and IRF7, resulting in impaired TRAF6-mediated IRF7 ubiquitination (PubMed:22095711). Interacts with TARBP2; this interaction prevents IRF7 phosphorylation and activation (By similarity).|||Nucleus|||Sumoylated by TRIM28, which inhibits its transactivation activity.|||TRAF6-mediated ubiquitination is required for IRF7 activation (PubMed:15361868, PubMed:22095711). TRIM35 mediates IRF7 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation (By similarity). 'Lys-48'-linked polyubiquitination and subsequent proteasomal degradation is NMI-dependent in response to Sendai virus infection (PubMed:23956435). Ubiquitinated by UBE3C, leading to its degradation (By similarity). http://togogenome.org/gene/10090:Yju2b ^@ http://purl.uniprot.org/uniprot/Q9D516 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CWC16 family.|||May be involved in mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Entpd7 ^@ http://purl.uniprot.org/uniprot/Q3TCT4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GDA1/CD39 NTPase family.|||Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner. Preferentially hydrolyzes nucleoside 5'-triphosphates, with substrate preference for UTP > GTP > CTP. Hydrolyzes nucleoside diphosphates only to a minor extent (By similarity). In contrast to its human ortholog is able to hydrolyze ATP. In the epithelial cells of small intestine controls luminal ATP levels, therefore regulating Th17-cell development (PubMed:23241884).|||Cytoplasmic vesicle membrane|||Deficient mice are born at the normal Mendelian ratios and grow healthily until 16 week of age. Normal lymphocyte development is observed. However deficient mice shown an increased in ATP concentrations in the small intestinal lumen and increased numbers of IL-17-producing Th17 cells in the small intestinal lamina propria. They show increased resistance to Citrobacter rodentium infection and increased susceptibility to experimental autoimmune encephalomyelitis.|||Widely expressed. Expressed at high level in brain, kidney, liver, testis and small intestin. Weakly expressed in lung, thymus and heart. http://togogenome.org/gene/10090:Ermn ^@ http://purl.uniprot.org/uniprot/Q5EBJ4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds actin.|||Brain and spinal cord. Exclusively expressed by the oligodendrocytes. Appears at a late stage during myelination, and in the mature nerves, it is localized to the outer cytoplasmic lip of the myelin sheath and the paranodal loops.|||Plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis as well as in maintenance and stability of myelin sheath in the adult. May play an important role in late-stage oligodendroglia maturation, myelin/Ranvier node formation during CNS development, and in the maintenance and plasticity of related structures in the mature CNS (By similarity).|||Weakly detectable in the first 3 postnatal days, but increases during the initial 2 weeks after birth.|||cytoskeleton http://togogenome.org/gene/10090:Rnase12 ^@ http://purl.uniprot.org/uniprot/Q5GAM8|||http://purl.uniprot.org/uniprot/W0UUY1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pancreatic ribonuclease family.|||Does not exhibit any ribonuclease activity.|||Secreted http://togogenome.org/gene/10090:Vmn2r104 ^@ http://purl.uniprot.org/uniprot/E9Q2J5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zmym4 ^@ http://purl.uniprot.org/uniprot/A2A791 ^@ Function ^@ Plays a role in the regulation of cell morphology and cytoskeletal organization. http://togogenome.org/gene/10090:Col19a1 ^@ http://purl.uniprot.org/uniprot/Q0VF58 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.|||Expressed in the myotome of somites from 9.5 dpc. In muscular tissues, expression is transient and is confined to a few sites of the developing embryo, such as limbs, tongue, and smooth muscle layers of stomach and esophagus. Also detected in skin at 16.5 dpc and in cerebral cortex and hippocampus of the newborn brain. In adult, expression is only observed in cerebrum, cerebellum, eyes, and testis. In CNS, expression gradually increases following birth. Also expressed in embryonic fibroblasts and to a lesser extent in adult fibroblasts.|||May act as a cross-bridge between fibrils and other extracellular matrix molecules. Involved in skeletal myogenesis in the developing esophagus. May play a role in organization of the pericellular matrix or the sphinteric smooth muscle.|||Mice show severe signs of malnourishment and the majority die within the first three weeks of postnatal life. Newborn homozygotes do not show gross anatomical abnormalities, except for smaller size of the internal organs. However, necroscopy of the mice that survive past the weaning stage reveals a dilated esophagus (megaesophagus) with retention of ingesta immediately above the diaphragm level. Mutant mice also exhibit an additional defect, namely impaired smooth-to-skeletal muscle cell transdifferentiation in the abdominal segment of the esophagus. Heterozygotes by comparison are morphologically normal, viable and fertile.|||Oligomer; disulfide-linked.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The numerous interruptions in the triple helix may make this molecule either elastic or flexible.|||extracellular matrix http://togogenome.org/gene/10090:Cox8b ^@ http://purl.uniprot.org/uniprot/P48772|||http://purl.uniprot.org/uniprot/Q545U6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIII family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Mcmbp ^@ http://purl.uniprot.org/uniprot/Q8R3C0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated component of the MCM complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion (By similarity).|||Belongs to the MCMBP family.|||Interacts with the MCM complex: associates with the MCM3-7 complex which lacks MCM2, while it does not interact with the MCM complex when MCM2 is present (MCM2-7 complex). Interacts with the RPA complex, when composed of all RPA1, RPA2 and RPA3 components, but not with RPA1 or RPA2 alone (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ftcd ^@ http://purl.uniprot.org/uniprot/Q91XD4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Binds and promotes bundling of vimentin filaments originating from the Golgi.|||Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool (By similarity).|||Golgi apparatus|||Homooctamer, including four polyglutamate binding sites. The subunits are arranged as a tetramer of dimers, and form a planar ring-shaped structure (By similarity).|||In the C-terminal section; belongs to the cyclodeaminase/cyclohydrolase family.|||In the N-terminal section; belongs to the formiminotransferase family.|||centriole http://togogenome.org/gene/10090:Or10x1 ^@ http://purl.uniprot.org/uniprot/F8VQB1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or10j7 ^@ http://purl.uniprot.org/uniprot/E9Q8X1|||http://purl.uniprot.org/uniprot/Q8VG31 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dmrta1 ^@ http://purl.uniprot.org/uniprot/Q8CFG4 ^@ Developmental Stage|||Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DMRT family.|||Expressed in gonads from 11.5 dpc onward. Expressed in the genital ridge at 11.5 dpc and in the seminiferous tubules at 12.5 dpc.|||Mutant animals are viable and fertile, with no obvious anatomical defects. Ovaries from mutant females may have an elevated number of polyovular follicles. 25% of mutant males consistently exhibit copulatory behavior toward other males.|||Nucleus|||Widely expressed, with highest levels in ovary, testis, epididymis, preputial gland, vomeronasal organ, liver, salivary glands and heart. Also expressed throughout the brain with highest levels in the olfactory bulbs and medulla. Detected at similar levels in gonads of both sexes. http://togogenome.org/gene/10090:Lmod2 ^@ http://purl.uniprot.org/uniprot/Q3UHZ5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tropomodulin family.|||Can bind at least three actin monomers and thereby provides a nucleus for actin filament formation. Interacts (via N-terminus) with tropomyosin alpha (TPM1) (via N-terminus). May also interact with TPM2 (via N-terminus) (PubMed:17572376).|||Detected in neonate heart (at protein level) (PubMed:26487682). Detected in embryonic heart and in pharyngeal arches (PubMed:26487682). Detected in adult heart (PubMed:27274810).|||M line|||Mediates nucleation of actin filaments and thereby promotes actin polymerization (By similarity). Plays a role in the regulation of actin filament length (PubMed:26487682). Required for normal sarcomere organization in the heart, and for normal heart function (PubMed:26487682, PubMed:27274810).|||Mutant mice are born at the expected Mendelian rate. All die between 15 to 33 days after birth due to early-onset dilated cardiomyopathy. Cardiac muscle thin filaments are shorter than in wild-type, both in embryonic heart and in pups 6 or 15 days after birth. Hearts appear grossly normal at birth, but after 15 days, they display enlarged left ventricles with thin ventricle walls and resuced systolic performance. In contrast, there are no differences in thin filament length in skeletal muscle (PubMed:26487682). Insertion of a transposon in the first, non-coding exon decreases Lmod2 expression by 90% in females and by over 95% in males and gives rise to a phenotype that is closely similar to that of complete gene disruption, except that mutant mice die between three and nine weeks after birth (PubMed:27274810).|||cytoskeleton|||myofibril|||sarcomere http://togogenome.org/gene/10090:Or51t4 ^@ http://purl.uniprot.org/uniprot/F8VQ18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pde10a ^@ http://purl.uniprot.org/uniprot/A0A384DV92|||http://purl.uniprot.org/uniprot/Q7TPG2|||http://purl.uniprot.org/uniprot/Q8CA95 ^@ Cofactor|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.|||Detected in striatum (at protein level). Detected in testis and brain.|||Down-regulated by the expression of a huntingtin (HD) gene with an expanded polyglutamine repeat prior to the onset of neurological symptoms related to Huntington disease.|||Homodimer.|||Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10359840). Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10359840). May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:10359840, PubMed:14751289, PubMed:27058446).|||The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity (By similarity).|||cytosol http://togogenome.org/gene/10090:Samd1 ^@ http://purl.uniprot.org/uniprot/D3YXK1 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expressed to similar levels in different organs. Expressed at higher levels in bone marrow, osteoclasts and spleen (PubMed:33980486). Expressed in vascular smooth muscle cells (PubMed:34006929).|||Expression is inhibited by miRNA MIR378C (PubMed:34006929). Expression is induced by PDGF (PubMed:34006929).|||Homopolymerize into a closed pentameric ring (By similarity). Interacts (via SAM domain) with L3MBTL3 (via SAM domain); the interaction mediates L3MBTL3 binding to chromatin (PubMed:33980486). Interacts (via WH domain) with KDM1A; the interaction modulates KDM1A function (PubMed:33980486).|||Nucleus|||Secreted|||Unmethylated CpG islands (CGIs)-binding protein which localizes to H3K4me3-decorated CGIs, where it acts as a transcriptional repressor (PubMed:33980486, PubMed:34006929). Tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs (PubMed:33980486). Plays a role in atherogenesis by binding with LDL on cell surface and promoting LDL oxidation which leads to the formation of foam cell (PubMed:34006929).|||Winged-helix (WH) domain directly recognizes and binds unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove of DNA. http://togogenome.org/gene/10090:Ogfr ^@ http://purl.uniprot.org/uniprot/Q99PG2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the opioid growth factor receptor family.|||Cytoplasm|||Expressed in all tissues examined, including brain, heart, lung, liver, kidney and skeletal muscle.|||Nucleus|||Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation (By similarity). http://togogenome.org/gene/10090:Syngr1 ^@ http://purl.uniprot.org/uniprot/O55100|||http://purl.uniprot.org/uniprot/Q3U6D7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptogyrin family.|||May play a role in regulated exocytosis. Modulates the localization of synaptophysin/SYP into synaptic-like microvesicles and may therefore play a role in synaptic-like microvesicle formation and/or maturation (By similarity). Involved in the regulation of short-term and long-term synaptic plasticity (PubMed:10595519).|||Melanosome|||Membrane|||Mice lacking both Syngr1 and Syp show normal brain structure and composition, but impaired short-term and long-term synaptic plasticity.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Or10ad1 ^@ http://purl.uniprot.org/uniprot/E9PZS7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wdr47 ^@ http://purl.uniprot.org/uniprot/Q8CGF6 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Enriched in the nervous system (at protein level).|||First detected in whole embryos at 11 dpc, strong and increasing protein levels are observed in the brain from 14 dpc to early postnatal development. Expression continues into adulthood, though at a substantially decreased level.|||Interacts with MAP1S (via WD repeats).|||cytoskeleton http://togogenome.org/gene/10090:Bltp2 ^@ http://purl.uniprot.org/uniprot/Q5SYL3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SABRE family.|||Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Endoplasmic reticulum membrane|||Mitochondrion membrane|||Tube-forming lipid transport protein which binds to phosphatidylinositols and affects phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) distribution. http://togogenome.org/gene/10090:Bcl2a1d ^@ http://purl.uniprot.org/uniprot/O55179 ^@ Similarity ^@ Belongs to the Bcl-2 family. http://togogenome.org/gene/10090:Psma5 ^@ http://purl.uniprot.org/uniprot/Q3UPK6|||http://purl.uniprot.org/uniprot/Q9Z2U1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). PSMA5 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly (By similarity). http://togogenome.org/gene/10090:Or9s15 ^@ http://purl.uniprot.org/uniprot/Q8VFC4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nme3 ^@ http://purl.uniprot.org/uniprot/Q9WV85 ^@ Function|||Similarity ^@ Belongs to the NDK family.|||Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Probably has a role in normal hematopoiesis by inhibition of granulocyte differentiation and induction of apoptosis (By similarity). http://togogenome.org/gene/10090:Mon1a ^@ http://purl.uniprot.org/uniprot/A0A0R4J0D5|||http://purl.uniprot.org/uniprot/Q6PDG8 ^@ Function|||Polymorphism|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the MON1/SAND family.|||Interacts with CCZ1 (By similarity). Found in a complex with RMC1, CCZ1, MON1A and MON1B (By similarity). The MON1A-CCZ1B complex interacts with RIMOC1 (By similarity). The MON1A-CCZ1B complex interacts with RAB7A and this interaction is enhanced in the presence of RIMOC1 (By similarity).|||Plays an important role in membrane trafficking through the secretory apparatus.|||Plays an important role in membrane trafficking through the secretory apparatus. Not involved in endocytic trafficking to lysosomes (PubMed:17632513). Acts in concert with CCZ1, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form (By similarity).|||The variant Ser-374 is unique to C57BL strains. It may confer the low iron phenotype observed in these strains.|||Widely expressed (at protein level). http://togogenome.org/gene/10090:Serpina3c ^@ http://purl.uniprot.org/uniprot/P29621 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Ano2 ^@ http://purl.uniprot.org/uniprot/Q8CFW1 ^@ Activity Regulation|||Developmental Stage|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Calcium-activated chloride channel (CaCC) which may play a role in olfactory signal transduction. Odorant molecules bind to odor-sensing receptors (OSRs), leading to an increase in calcium entry that activates CaCC current which amplifies the depolarization of the OSR cells, ANO2 seems to be the underlying chloride channel involved in this process. May mediate light perception amplification in retina.|||Cell membrane|||Channel activity is repressed by chloride inhibitors; strongly by niflumic acid (NFA), partially by flufenamic acid (FFA), and only slightly by meclofenamic acid (MFA), 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 4-acetamido-4'-isothiocyanato-stilben-2,2'-disulfonate (SITS), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS).|||Component of a presynaptic protein complex recruited to specialized plasma membrane domains of photoreceptors. Interacts with DLG4 by its C-terminal region.|||Detected in the mantle layer of the neural tube and in the dorsal root ganglia at 14.5 dpc. In developing skin, expression is restricted to basal layers of the epidermis at 16.5 dpc.|||Expressed in retina, especially in the photoreceptor synaptic terminals, and in olfactory epithelium, particularly in sensory neurons (OSNs) and cilia (at protein level). Also observed in retinal pigment epithelium (RPE), olfactory bulb, brain, and cortex.|||Glycosylated.|||Probable cloning artifact.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Ccdc47 ^@ http://purl.uniprot.org/uniprot/Q0VBU4|||http://purl.uniprot.org/uniprot/Q9D024 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC47 family.|||CCDC47 knockout leads to embryonic lethality at mid-gestation, between 10.5 and 11.5 dpc. Mutant embryos at 8.5-10.5 dpc reveal several anomalies including vascular abnormalities in yolk sacs, developmental retardation, atrophic neural tubes, dilated left ventricles, poorly developed myocardium, and paucity of blood cells in the dorsal aorta. Yolk sac endoderm cells show alterations associated with endoplasmic reticulum stress, including lipid droplet accumulation, endoplasmic reticulum fragmentation and dissociation of ribosomes.|||Component of the PAT complex, composed of WDR83OS/Asterix and CCDC47 (By similarity). The PAT complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47) (By similarity). The MPT complex associates with the SEC61 complex (By similarity). Interacts with VCP, HSPA5, DERL1, DERL2 and SELENOS (PubMed:25009997).|||Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (By similarity). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity). Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein (By similarity). Within the PAT subcomplex, CCDC47 occludes the lateral gate of the SEC61 complex (By similarity). Involved in the regulation of calcium ion homeostasis in the ER (By similarity). Required for proper protein degradation via the ERAD (ER-associated degradation) pathway (By similarity). Has an essential role in the maintenance of ER organization during embryogenesis (PubMed:25009997).|||Endoplasmic reticulum membrane|||In the embryo, expressed in the endodermal layer of the yolk sac and in the small intestine.|||Rough endoplasmic reticulum membrane http://togogenome.org/gene/10090:Aff2 ^@ http://purl.uniprot.org/uniprot/O55112 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AF4 family.|||Expressed before day 7 in the embryo and reached its highest levels at 10.5-11.5 days. In the embryo at day 11, expression is more specific in the roof of the hind brain and the lateral ventricle of the brain.|||Highly expressed in the hippocampus, the piriform cortex, Purkinje cells and the cingulate gyrus.|||Nucleus speckle|||RNA-binding protein. Might be involved in alternative splicing regulation through an interaction with G-quartet RNA structure. http://togogenome.org/gene/10090:Lgals2 ^@ http://purl.uniprot.org/uniprot/Q9CQW5 ^@ Function|||Subunit ^@ Homodimer.|||This protein binds beta-galactoside. Its physiological function is not yet known. http://togogenome.org/gene/10090:Mdp1 ^@ http://purl.uniprot.org/uniprot/Q9D967 ^@ Activity Regulation|||Function|||Similarity ^@ Belongs to the HAD-like hydrolase superfamily.|||Inhibited by vanadate and zinc, and slightly by calcium.|||Magnesium-dependent phosphatase which may act as a tyrosine phosphatase. http://togogenome.org/gene/10090:Pa2g4 ^@ http://purl.uniprot.org/uniprot/P50580|||http://purl.uniprot.org/uniprot/Q3TGU7 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the peptidase M24 family, it does not contain metal cofactors and lacks aminopeptidase activity.|||Belongs to the peptidase M24 family.|||By mitogens.|||Cytoplasm|||Expressed in proliferating cells. Observed between G1 and mid S phase, decrease toward the end of S phase, and disappear at the S/G2 transition.|||Isoform 2 interacts with the cytoplasmic domain of non-phosphorylated ERBB3; the interaction requires PKC activity. Interacts with AR. Treatment with HRG leads to dissociation from ERBB3 and increases association with AR. Interacts with nucleolin/NCL. Component of a ribonucleoprotein complex containing at least PA2G4, NCL, TOP1, PABPC2, RPLP0, acetylated histone H1 (HIST1H1A or H1F1), histone H1 2/4, RPL4, RPL8, RPL15, RPL18, RPL18A, RPL21, RPL11, RPL12, RPL28, RPL27, RPLP2 and RPL24. Interacts with HDAC2. Interacts with RB1; the interaction is enhanced upon PA2G4 dephosphorylation (By similarity). Interacts with AKT1 (By similarity). Isoform 1 and isoform 2 interact with RNF20 (By similarity). Isoform 2 interacts with HUWE1. Interacts with DNAJC21 (By similarity).|||Isoform 2 is polyubiquitinated, leading to proteasomal degradation and phosphorylation by PKC/PRKCD enhances polyubiquitination.|||May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly (By similarity). Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site). Together with PTBP1 is required for the translation initiation on the foot-and-mouth disease virus (FMDV) IRES. Regulates cell proliferation, differentiation, and survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes cell differentiation (By similarity).|||Phosphorylated on serine and threonine residues. Phosphorylation is enhanced by HRG treatment. Basal phosphorylation is PKC-dependent and HRG-induced phosphorylation is predominantly PKC-independent. Phosphorylation at Ser-361 by PKC/PRKCD regulates its nucleolar localization.|||Widely expressed.|||nucleolus http://togogenome.org/gene/10090:Slc4a4 ^@ http://purl.uniprot.org/uniprot/A2VDF7|||http://purl.uniprot.org/uniprot/A7E1Z5|||http://purl.uniprot.org/uniprot/E9Q8N8|||http://purl.uniprot.org/uniprot/O88343 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by cyclic AMP.|||Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.|||Homodimer (By similarity). Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity (PubMed:14567693, PubMed:15218065). Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity (PubMed:16769890, PubMed:19033647, PubMed:21317537). Interacts with AHCYL2 (By similarity).|||Isoform 1 is specifically expressed in pancreatic ducts and acini (PubMed:19033647). Also expressed in parotid acinar cells and in the colonic crypts.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lateral cell membrane|||Membrane|||N-glycosylated. May not be necessary for the transporter basic functions.|||Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1 to 2:1. Phosphorylated in presence of STK39 and dephosphorylated in presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4 activity (PubMed:21317537). http://togogenome.org/gene/10090:Fat4 ^@ http://purl.uniprot.org/uniprot/Q2PZL6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherins are cell-cell interaction molecules. FAT4 plays a role in the maintenance of planar cell polarity as well as in inhibition of YAP1-mediated neuroprogenitor cell proliferation and differentiation.|||Deficient mice exhibit postnatal lethality, growth retardation, small lungs, abnormal cochlea morphology, abnormal kidney morphology, cardiovascular abnormalities and skeletal abnormalities. DCHS1 and FAT4 single mutants and DCHS1/FAT4 double mutants have similar phenotypes.|||Expressed in all layers of the developing brain, with expression being most prominent at the ventricular margin.|||Heterophilic interaction with DCHS1; this interaction affects their respective protein levels. Interacts (via cytoplasmic domain) with MPDZ. Forms a complex with PALS1 and MPDZ.|||Membrane|||Widely expressed. http://togogenome.org/gene/10090:Mfsd13a ^@ http://purl.uniprot.org/uniprot/Q6PDE8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Lrrc66 ^@ http://purl.uniprot.org/uniprot/Q8K0B3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pxylp1 ^@ http://purl.uniprot.org/uniprot/Q8BHA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histidine acid phosphatase family.|||Golgi apparatus membrane|||Interacts with B3GAT3; the interaction increases the 2-phosphoxylose phosphatase activity of PXYLP1 during completion of linkage region formation in a B3GAT3-mediated manner.|||Responsible for the 2-O-dephosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature glycosaminoglycan (GAG) chains. Sulfated glycosaminoglycans (GAGs), including heparan sulfate and chondroitin sulfate, are synthesized on the so-called common GAG-protein linkage region (GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser) of core proteins, which is formed by the stepwise addition of monosaccharide residues by the respective specific glycosyltransferases. Xylose 2-O-dephosphorylation during completion of linkage region formation is a prerequisite for the initiation and efficient elongation of the repeating disaccharide region of GAG chains. http://togogenome.org/gene/10090:Ccnl1 ^@ http://purl.uniprot.org/uniprot/Q52KE7 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family. Cyclin L subfamily.|||Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions (By similarity).|||Cytoplasm|||Found both in the nucleus and cytoplasm.|||Found in the nucleus, with a speckled pattern of expression.|||Interacts with POLR2A via its hyperphosphorylated C-terminal domain (CTD) (By similarity). Interacts with CDK11A, CDK11B, CDK12 and CDK13. May form a ternary complex with CDK11B and casein kinase II (CKII). Interacts with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 and SRSF7/SLU7 (By similarity) (PubMed:17261272).|||Involved in pre-mRNA splicing. Functions in association with cyclin-dependent kinases (CDKs). May play a role in the regulation of RNA polymerase II (pol II). Inhibited by the CDK-specific inhibitor CDKN1A/p21.|||Nucleus|||Nucleus speckle|||Widely expressed (at protein level).|||nucleoplasm http://togogenome.org/gene/10090:Klhl42 ^@ http://purl.uniprot.org/uniprot/Q8BFQ9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL42. Interacts (via the BTB domain) with CUL3. Interacts (via the kelch domains) with KATNA1 (By similarity).|||Cytoplasm|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL42) E3 ubiquitin ligase complex mediates the ubiquitination and subsequent degradation of KATNA1. Involved in microtubule dynamics throughout mitosis (By similarity).|||spindle http://togogenome.org/gene/10090:Defb33 ^@ http://purl.uniprot.org/uniprot/Q30KN3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Serpina3g ^@ http://purl.uniprot.org/uniprot/Q3U0Y1|||http://purl.uniprot.org/uniprot/Q5I2A0 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Cytoplasm|||Expressed in bone marrow (particularly hematopoietic stem cells), heart, kidney, liver, lung, skeletal muscle, spleen, testis, thymus and T-cells.|||Induction during apoptosis requires NF-kappa-B, a heterodimer of RELA- and NFKB1.|||Nucleus|||Serine and cysteine protease inhibitor. Can inhibit lysosomal papain-like proteases including the cathepsins B, G, H, K, L and V. Ineffective against elastase, granzyme A, granzyme B, or caspases 3, 8 or 9. Inhibition of cytoplasmic cathepsin B following release from the lysosome may protect cells from apoptosis. This may facilitate the survival of progenitor T-cells and the subsequent development of long term memory CD8 T-cells.|||T-cell specific expression rises during the differentiation of CD8 T-cell progenitors into memory CD8 T-cells.|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Cyp3a44 ^@ http://purl.uniprot.org/uniprot/Q9EQW4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Cep128 ^@ http://purl.uniprot.org/uniprot/Q8BI22 ^@ Subcellular Location Annotation ^@ centriole|||spindle pole http://togogenome.org/gene/10090:Tgfbr1 ^@ http://purl.uniprot.org/uniprot/Q4FJL1|||http://purl.uniprot.org/uniprot/Q64729|||http://purl.uniprot.org/uniprot/Q9D5H8 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Cell surface|||Homodimer; in the endoplasmic reticulum but also at the cell membrane. Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer. The respective affinity of TGBRB1 and TGFBR2 for the ligands may modulate the kinetics of assembly of the receptor and may explain the different biological activities of TGFB1, TGFB2 and TGFB3. Component of a complex composed of TSC22D1 (via N-terminus), TGFBR1 and TGFBR2; the interaction between TSC22D1 and TGFBR1 is inhibited by SMAD7 and promoted by TGFB1 (By similarity). Interacts with CD109; inhibits TGF-beta receptor activation in keratinocytes. Interacts with RBPMS. Interacts (unphosphorylated) with FKBP1A; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation. Interacts with SMAD2, SMAD3 and ZFYVE9; ZFYVE9 recruits SMAD2 and SMAD3 to the TGF-beta receptor. Interacts with TRAF6 and MAP3K7; induces MAP3K7 activation by TRAF6. Interacts with PARD6A; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with NEDD4L (By similarity). Interacts with SMAD7, SMURF1 and SMURF2; SMAD7 recruits NEDD4L, SMURF1 and SMURF2 to the TGF-beta receptor (By similarity). Interacts with USP15 and VPS39. Interacts with SDCBP (via C-terminus) (By similarity). Interacts with CAV1 and this interaction is impaired in the presence of SDCBP (By similarity). Interacts with APPL1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (By similarity).|||Kept in an inactive conformation by FKBP1A preventing receptor activation in absence of ligand. CD109 is another inhibitor of the receptor (By similarity).|||May be due to a competing donor splice site.|||Membrane|||Membrane raft|||N-Glycosylated.|||Phosphorylated at basal levels in the absence of ligand. Activated upon phosphorylation by TGFBR2, mainly in the GS domain. Phosphorylation in the GS domain abrogates FKBP1A-binding (By similarity).|||Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation (By similarity).|||Ubiquitinated; undergoes ubiquitination catalyzed by several E3 ubiquitin ligases including SMURF1, SMURF2 and NEDD4L2. Results in the proteasomal and/or lysosomal degradation of the receptor thereby negatively regulating its activity. Deubiquitinated by USP15, leading to stabilization of the protein and enhanced TGF-beta signal. Its ubiquitination and proteasome-mediated degradation is negatively regulated by SDCBP (By similarity).|||tight junction http://togogenome.org/gene/10090:Tdrd6 ^@ http://purl.uniprot.org/uniprot/P61407 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Found in a mRNP complex (i.e. messenger ribonucleoproteins which correspond to mRNA with bound proteins), at least composed of TDRD1, TDRD6, TDRD7 and DDX4 (PubMed:17141210). Found in a complex, at least composed of PIWIL1, PIWIL2, DDX4 and TDRD6 (PubMed:19345099, PubMed:19584108, PubMed:19926723). Interacts with Tex19.1 and probably Tex19.2 (PubMed:28254886). Interacts with PRMT5 (PubMed:28263986). Interacts with SNRPB (when methylated); to trigger spliceosome formation (PubMed:28263986).|||Males are sterile (elongated spermatids are almost completely lacking), but viable (PubMed:19345099). Chromatoid body (CB) components mislocalize and CB architecture is distorted in round spermatids (PubMed:19345099). miRNA expression is altered (PubMed:19345099). Knockout spermatids are accompanied by distortion of chromatoid body structure, preventing UPF1-DDX4 and UPF1-UPF2 interactions, as well as disturbed association of several mRNAs with UPF1 and UPF2, and impaired long 3' UTR-triggered NMD (PubMed:27149095). Knockout diplotene spermatocytes display a reduction of PRMT5 association with SNRPB (also named SmB) and a reduction in arginine dimethylation of SNRPB, leading to an impairment in the assembly of spliceosomes (PubMed:28263986).|||Testis specific. Expressed in primary spermatocytes at post natal (PN) day 17.5. Expressed in midpachytene stage of primary spermatocytes at PN16 and in round spermatids at PN22 (at protein level).|||The tudor domains recognize and bind to proteins with dimethylated arginine residues.|||Tudor domain-containing protein involved in germ cell development, more specifically the formation of chromatoid body (during spermiogenesis), Balbiani body (during oogenesis), germ plasm (upon fertilization), and for proper miRNA expression and spliceosome maturation (PubMed:19345099, PubMed:27149095, PubMed:28263986) (By similarity). Essential for RNA-dependent helicase UPF1 localization to chromatoid body, for UPF1-UPF2 and UPF1-DDX4 interactions which are required for mRNA degradation, using the extended 3' UTR-triggered nonsense-mediated mRNA decay (NMD) pathway (PubMed:27149095). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through interaction with arginine N-methyltransferase PRMT5 and symmetrically arginine dimethylated SNRPB (small nuclear ribonucleoprotein-associated protein) (PubMed:28263986).|||Undergoes proteolytic cleavage near the C-terminal by an unknown protease during the transition from meiosis I to meiosis II in primary spermatocytes. http://togogenome.org/gene/10090:Rps17 ^@ http://purl.uniprot.org/uniprot/P63276|||http://purl.uniprot.org/uniprot/Q5M9L7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS17 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Ubiquitinated at Lys-103 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).|||nucleolus http://togogenome.org/gene/10090:Fam3a ^@ http://purl.uniprot.org/uniprot/A0A158SIT7|||http://purl.uniprot.org/uniprot/Q9D8T0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM3 family.|||Secreted http://togogenome.org/gene/10090:Ssna1 ^@ http://purl.uniprot.org/uniprot/Q9JJ94 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SSNA1 family.|||Microtubule-binding protein which stabilizes dynamic microtubules by slowing growth and shrinkage at both plus and minus ends and serves as a sensor of microtubule damage, protecting microtubules from the microtubule-severing enzyme SPAST (By similarity). Induces microtubule branching which is mediated by the formation of long SSNA1 fibrils which guide microtubule protofilaments to split apart from the mother microtubule and form daughter microtubules (By similarity). Plays a role in axon outgrowth and branching (PubMed:30250060). Required for cell division (By similarity).|||Midbody|||Nucleus|||Self-associates to form fibrils. Also forms dimers as well as monomers. Interacts with SPAST.|||axon|||centriole|||centrosome|||flagellum axoneme|||flagellum basal body http://togogenome.org/gene/10090:Ap4s1 ^@ http://purl.uniprot.org/uniprot/Q9WVL1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1).|||Belongs to the adaptor complexes small subunit family.|||Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways. AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Esr1 ^@ http://purl.uniprot.org/uniprot/E7FJU2|||http://purl.uniprot.org/uniprot/P19785 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Binds DNA as a homodimer.|||Cell membrane|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner (By similarity).|||Cytoplasm|||Dimethylated by PRMT1 at Arg-264. The methylation may favor cytoplasmic localization. Demethylated by JMJD6 at Arg-264.|||Golgi apparatus|||Interacts with BCAS3. Binds DNA as a homodimer (By similarity). Can form a heterodimer with ESR2 (By similarity). Interacts with coactivator NCOA5. Interacts with PELP1, the interaction is enhanced by 17-beta-estradiol; the interaction increases ESR1 transcriptional activity (By similarity). Interacts with NCOA7; the interaction is ligand-inducible. Interacts with AKAP13, CUEDC2, HEXIM1, KDM5A, MAP1S, SMARD1, and UBE1C. Interacts with MUC1; the interaction is stimulated by 7 beta-estradiol (E2) and enhances ESR1-mediated transcription. Interacts with DNTTIP2, and UIMC1. Interacts with KMT2D/MLL2. Interacts with ATAD2; the interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via its C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interacts with SH2D4A; the interaction blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62; the interaction requires estradiol and appears to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DNAAF4. Interacts with PRMT2. Interacts with RBFOX2. Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent (By similarity). Interacts with FAM120B, FOXL2, PHB2 and SLC30A9. Interacts with coactivators NCOA3 and NCOA6. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5. Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3. Interacts with NRIP1 (By similarity). Interacts with GPER1; the interaction occurs in an estrogen-dependent manner. Interacts with CLOCK and the interaction is stimulated by estrogen (By similarity). Interacts with BCAS3. Interacts with TRIP4 (ufmylated); estrogen dependent (By similarity). Interacts with LMTK3; the interaction phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with ZFHX3 (By similarity). Interacts with SFR1 in a ligand-dependent and -independent manner (By similarity). Interacts with DCAF13, LATS1 and DCAF1; regulates ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation (By similarity). Interacts (via DNA-binding domain) with POU4F2 isoform 2 (C-terminus); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner (PubMed:9448000). Interacts with ESRRB isoform 1 (By similarity). Interacts with UBE3A and WBP2 (By similarity). Interacts with GTF2B (By similarity). Interacts with RBM39 (PubMed:11704680). In the absence of hormonal ligand, interacts with TACC1 (By similarity). Interacts with PI3KR1 or PI3KR2 and PTK2/FAK1 (By similarity). Interacts with SRC (By similarity).|||Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3.|||Nucleus|||Palmitoylated at Cys-451 by ZDHHC7 and ZDHHC21. This modification is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor.|||Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Dephosphorylation at Ser-122 by PPP5C inhibits its transactivation activity (By similarity). Phosphorylated by LMTK3 (in vitro) (By similarity).|||The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.|||Ubiquitinated. Deubiquitinated by OTUB1 (By similarity).|||Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation. Deubiquitinated by OTUB1. http://togogenome.org/gene/10090:Or1o4 ^@ http://purl.uniprot.org/uniprot/Q8VFE4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcsk1n ^@ http://purl.uniprot.org/uniprot/Q9QXV0 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Broadly expressed from 9 dpc to 11 dpc, with some enrichment in neural tube-derived tissues. By 15 dpc, the expression is largely restricted to neuroendocrine tissues.|||Endogenous ligand for GPR171 (PubMed:24043826). Neuropeptide involved in the regulation of feeding (PubMed:24043826).|||Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding.|||Expressed in brain (mostly hypothalamus and pituitary) and gut. Expressed in trigeminal ganglia and neuroendocrine cell lines.|||Expressed in pancreas, spinal cord and brain (most abundant in striatum, hippocampus, pons and medulla, and cortex) (at protein level).|||Interacts via the C-terminal inhibitory domain with PCSK1 66 kDa form.|||May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 87 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity.|||ProSAAS(1-180) increases secretion of enzymatically inactive PCSK1.|||Proteolytically cleaved in the Golgi. Little SAAS, PEN, PEN-20 and Big LEN are the major processed peptides in proSAAS-overexpressing AtT-20 pituitary corticotropic cell line.|||Secreted|||The C-terminal inhibitory domain is involved in inhibition of PCSK1. It corresponds to the probable processing intermediate Big PEN-LEN, binds to PCSK1 in vitro and contains the hexapeptide L-L-R-V-K-R, which, as a synthetic peptide, is sufficient for PCSK1 inhibition.|||The four C-terminal amino acids of Big LEN are sufficient to bind and activate GPR171.|||trans-Golgi network http://togogenome.org/gene/10090:Rab6a ^@ http://purl.uniprot.org/uniprot/P35279 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Golgi apparatus membrane|||Interacts (GTP-bound) with DYNLRB1; the interaction is direct (By similarity). Interacts with BICD1 (By similarity). Interacts with BICD2; the interaction is direct (By similarity). Interacts (GTP-bound) with VPS13B (By similarity).|||Interacts with BICD1 (By similarity). Interacts (GDP-bound) with DYNLRB1; the interaction is direct (By similarity). Interacts (GTP-bound) with VPS13B (By similarity).|||Interacts with BICDL1; leads to its accumulation in the pericentrosomal region (PubMed:20360680). Interacts with SCYL1BP1 (PubMed:18997784). Interacts with VSP52 (By similarity). Interacts with RABGAP1 (By similarity). Interacts with GCC2 (via its GRIP domain) (By similarity). Interacts with RAB6IP1 (via its RUN 1 domain) (By similarity). Interacts with TMF1 (By similarity). Interacts with CIMAP3 (PubMed:20643351). Interacts (GTP-bound) with APBA1/MINT1 isoform 3, also called Mint1_826, but not with isoform 1 (PubMed:23737971). Interacts with RIC1; the interaction is direct with a preference for RAB6A-GDP (By similarity). Interacts with RGP1; the interaction is direct with a preference for RAB6A-GDP (By similarity).|||Prenylated.|||Regulator of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER). Has a low GTPase activity. Involved in COPI-independent retrograde transport from the Golgi to the ER. Recruits VPS13B isoform 2 to the Golgi membrane. Plays a role in neuron projection development.|||acrosome membrane http://togogenome.org/gene/10090:Foxo4 ^@ http://purl.uniprot.org/uniprot/B1AUT3|||http://purl.uniprot.org/uniprot/Q4KL34|||http://purl.uniprot.org/uniprot/Q9WVH3 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation by CREBBP/CBP is induced by oxidative stress and inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity (By similarity).|||By artery ligation in proliferating neointimal smooth muscle cells.|||Cytoplasm|||Interacts with CREBBP/CBP, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CREBBP/CBP and deacetylated by SIRT1. Binding of YWHAZ inhibits DNA-binding. Interacts with USP7; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of TP53. Interacts with NLK, and this inhibits monoubiquitination and transcriptional activity (By similarity). Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (PubMed:22956541).|||Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors; results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7; deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently, deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity. Hydrogene-peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein stability (By similarity).|||Nucleus|||Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK (By similarity).|||Strongly expressed in brown adipose tissue and weakly in white adipose tissue (at protein level). Expressed in skeletal muscle.|||Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity (By similarity). Represses smooth muscle cell differentiation by inhibiting the transcriptional coactivator activity of myocardin. http://togogenome.org/gene/10090:Acaca ^@ http://purl.uniprot.org/uniprot/Q5SWU9 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 2 magnesium or manganese ions per subunit.|||Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain. The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA.|||Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20952656). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20952656).|||Inhibited by phosphorylation (By similarity). Citrate promotes oligomerization of the protein into filaments that correspond to the most active form of the carboxylase (PubMed:20952656).|||Monomer, homodimer, and homotetramer (PubMed:20952656). Can form filamentous polymers (PubMed:20952656). Interacts in its inactive phosphorylated form with the BRCT domains of BRCA1 which prevents ACACA dephosphorylation and inhibits lipid synthesis (PubMed:12360400). Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity (PubMed:20952656, PubMed:20457939).|||Phosphorylation at Ser-79 by AMPK inactivates enzyme activity.|||Phosphorylation on Ser-1262 is required for interaction with BRCA1.|||The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity.|||Up-regulated by endocannabinoid anandamide/AEA.|||cytosol http://togogenome.org/gene/10090:Tcp11l2 ^@ http://purl.uniprot.org/uniprot/Q8K1H7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP11 family.|||Interacts with FMNL2; this interaction promotes muscle-derived satellite cell (MDSC) migration and differentiation.|||Promotes the migration of muscle-derived satellite cells (MDSCs) during differentiation throught interaction with FMNL2 and therefore may participate in microfilament assembly.|||cytoskeleton http://togogenome.org/gene/10090:Vcl ^@ http://purl.uniprot.org/uniprot/Q64727 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated; mainly by myristic acid but also by a small amount of palmitic acid.|||Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion (By similarity).|||Belongs to the vinculin/alpha-catenin family.|||Cell membrane|||Exhibits self-association properties. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (By similarity). Interacts with APBB1IP, NRAP and TLN1. Interacts with SYNM. Interacts with CTNNB1 and this interaction is necessary for its localization to the cell-cell junctions and for its function in regulating cell surface expression of E-cadherin (By similarity). Interacts with SORBS1 (PubMed:10085297). Interacts with SYNM (By similarity). Interacts with CTNNA1 (By similarity). Binds to ACTN4; this interaction triggers conformational changes (By similarity).|||Exists in at least two conformations. When in the closed, 'inactive' conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an 'active' conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion.|||Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1065 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques (By similarity).|||The N-terminal globular head (Vh) comprises of subdomains D1-D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. An intramolecular interaction between Vh and Vt masks the F-actin-binding domain located in Vt. The binding of talin and alpha-actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin-binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly.|||adherens junction|||cytoskeleton|||focal adhesion|||podosome|||sarcolemma http://togogenome.org/gene/10090:Cyct ^@ http://purl.uniprot.org/uniprot/P00015 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome c family.|||Binds 1 heme c group covalently per subunit.|||Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.|||Mitochondrion intermembrane space|||Phosphorylation at Tyr-49 and Tyr-98 both reduce by half the turnover in the reaction with cytochrome c oxidase, down-regulating mitochondrial respiration.|||Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity).|||This is one of two isocytochromes C found in the testis. The other is identical with the form found in other mouse tissues. These cytochromes are assumed to be located in the sperm. http://togogenome.org/gene/10090:Hif3a ^@ http://purl.uniprot.org/uniprot/Q0VBL6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression (PubMed:9840812, PubMed:11734856, PubMed:21546903). Plays a role in the development of the cardiorespiratory system (PubMed:18070924).|||Acts as positive regulator of hypoxia-inducible gene expression. Associates to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters in a ARNT-dependent manner, and hence also participates in the transcriptional activation of reporter genes driven by HRE (PubMed:9840812).|||Attenuates the ability of transcription factor HIF1A, EPAS1 and the HIF1A-ARNT complex to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation (PubMed:18070924). Also plays a role in the development of the lung and heart during embryonic and neonatal stages (PubMed:18070924).|||Attenuates the ability of transcription factor HIF1A, EPAS1 and the HIF1A-ARNT complex to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. May act as a tumor suppressor (PubMed:11734856). May also be involved in apoptosis (PubMed:21546903).|||Contains a nuclear localization signal between amino acid positions 75 and 98. Contains a nuclear export signal between amino acid positions 228 and 272.|||Cytoplasm|||In normoxia, hydroxylated on Pro-487 in the oxygen-dependent degradation domain (ODD) by PHD. The hydroxylated proline promotes interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation (By similarity).|||Isoform 1 interacts with ARNT (PubMed:9840812). Isoform 2 interacts with HIF1A (PubMed:11734856, PubMed:21546903). Isoform 2 interacts EPAS1 (PubMed:21546903). Isoform 2 interacts (via C-terminus domain) with BAD; the interaction reduces the binding between BAD and BAX (PubMed:21546903). Isoform 2 (via C-terminus domain) interacts with BCL2L2 and MCL1 (PubMed:21546903). Interacts with VHL (By similarity).|||Isoform 2 is up-regulated in corneal epithelium cells under hypoxia (at protein level) (PubMed:11734856). Isoform 2 is up-regulated by hypoxia in a HIF1A-dependent manner (PubMed:12119283, PubMed:17355974). Isoform 3 is up-regulated by hypoxia (PubMed:18070924).|||Isoform 3 is expressed in brain, heart, lung, liver and kidney at 15.5 dpc. Isoform 3 is expressed in heart, lung, liver and kidney at 18.5 dpc.|||Isoform 3 is expressed in endothelial cells of vessels and capillaries in alveoli of the neonatal lung (at protein level) (PubMed:18070924). Expressed in lung, brain, heart and kidney (PubMed:9840812). Isoform 2 is expressed in heart and lung (PubMed:12119283). Isoform 2 is highly expressed in the epithelial cell layer of the cornea with lower expression in the layers of ganglion cells, inner nuclear cells, and rods and cones of the retina (PubMed:11734856). Isoform 2 is expressed in the cerebellum only in the Purkinje cell layer (PubMed:11734856).|||Mice appeared outwardly normal and are viable and fertile. Show hypertrophy of the right atrium and ventricle, disarrangement of striated muscle fibers in the heart, and pulmonary hyperplasia (PubMed:18070924).|||Mitochondrion|||Mutagenesis of Lys-75, Arg-76, Arg-97 and Arg-98 increase strongly cytoplasmic localization. Mutagenesis of Pro-228, Pro-229, Leu-271 and Leu-272 increase strongly nuclear localization.|||Nucleus|||Nucleus speckle|||Ubiquitinated; ubiquitination occurs in a VHL- and oxygen-dependent pathway and subsequently targeted for proteasomal degradation. http://togogenome.org/gene/10090:Phlpp1 ^@ http://purl.uniprot.org/uniprot/Q8CHE4 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 2 manganese ions per subunit.|||Cytoplasm|||Insensitive to okadaic acid. Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability.|||Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3 and PRKCB. Interacts with WDR48 and USP12 (By similarity).|||Isoforms 1 and 2 are expressed in the retina (PubMed:20089132).|||Membrane|||Nucleus|||Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (By similarity). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylates RAF1 inhibiting its kinase activity. May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (PubMed:17382888). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (PubMed:20080691). Involved in development and function of regulatory T-cells (PubMed:21498666).|||The PH domain is required for interaction with PRKCB and its dephosphorylation.|||Up-regulated in the hippocampus upon chronic methamphetamine treatment. http://togogenome.org/gene/10090:Or2f1 ^@ http://purl.uniprot.org/uniprot/Q7TRV7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Agap1 ^@ http://purl.uniprot.org/uniprot/A0A087WRF2|||http://purl.uniprot.org/uniprot/Q8BXK8 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, expression is restricted to neural tube, forebrain and midbrain.|||Belongs to the centaurin gamma-like family.|||Cytoplasm|||GAP activity stimulated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and, to a lesser extent, by phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidic acid potentiates PIP2 stimulation (By similarity).|||GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system (By similarity).|||Homodimer. Interacts with several subunits of the AP-3 protein complex: AP3M1, AP3S1 and AP3S2. Interacts with GUCY1A3 and GUCY1B3 (By similarity).|||Phosphorylated on tyrosines.|||The PH domain mediates AP-3 binding.|||Widely expressed, with highest levels in brain and kidney. http://togogenome.org/gene/10090:Or2f1b ^@ http://purl.uniprot.org/uniprot/Q8VGP4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptrh1 ^@ http://purl.uniprot.org/uniprot/Q8BW00 ^@ Function|||Similarity ^@ Belongs to the PTH family.|||Peptidyl-tRNA hydrolase that cleaves nascent chains-tRNAs that are not stably fixed in the P-site of 60S ribosome-nascent chain complexes (By similarity). Acts downstream of the ribosome-associated quality control (RQC) pathway to release non-ubiquitinated nascent chains from 60S and 80S ribosome-nascent chain complexes (By similarity). Does not act on ubiquitinated nascent chains, which are cleaved by ANKZF1 for degradation (By similarity). http://togogenome.org/gene/10090:Pdha2 ^@ http://purl.uniprot.org/uniprot/P35487 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Heterotetramer of two PDHA2 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (By similarity).|||Mitochondrion matrix|||Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA2; it is reactivated by dephosphorylation.|||Testis.|||The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. http://togogenome.org/gene/10090:Numb ^@ http://purl.uniprot.org/uniprot/Q9QZS3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Endosome membrane|||Expressed in neural progenitors and neuron cells throughout the developing nervous system. Expressed in somites and throughout the neural tube from 8.5 dpc, onward.|||Expressed in subventricular zone (SVZ) neuroprogenitors and ependymal cells.|||Interacts with SIAH1 (By similarity). Interacts with LNX (PubMed:9535908). Interacts with CDH1 (PubMed:17174898). Interacts with TFAP2A and TFAP2B (By similarity). Interacts with RALBP1 in a complex also containing EPN1 and TFAP2A during interphase and mitosis (By similarity). Interacts with AAK1 (By similarity). May interact with DUOXA1 (By similarity).|||Mutant animals exhibit severe defects in cranial neuronal tube closure and die around 11.5 dpc, but neurogenesis abnormalities are limited. Mice lacking both Numb and Numbl genes die around 9.5 dpc, with severe defects in somite and vasculature formation, neuronal tube closure and axial turning. Conditional mutants, with expression abrogated in neural progenitor cells from 8.5 dpc are viable, fertile and exhibit no obvious phenotypes. Conditional double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated in neural progenitor cells from 8.5 dpc (just before the onset of neurogenesis), display a loss of neuronal progenitor cells formation and an overexpression of neurons as neurogenesis progresses; cdKO mutants become necrotic at 12.5 dpc and die around this stage. Conditional double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated in neural progenitor cells from 10.5 dpc (just after the onset of neurogenesis), display a premature depletion of neural progenitor cells in the dorsal forebrain ventrical zone of the neocortex and in the hippocampal CA fields as neurogenesis progresses; cdKO mutants are viable and fertile, but showed a reduction in the thickness of the neocortex and the hippocampus and a enlargement of the lateral ventricles. Tamoxifen-inducible double-knockout (cdKO) mutants (Numb and Numbl genes), with expression abrogated postnatally in the subventricular zone (SVZ) neuroprogenitors and in ependymal cells, display a loss of SVZ neuroblasts and show a disorganized ependyma lacking both interdigitation junction between neighboring cells and increasing number of separated cells.|||Phosphorylated on Ser-276 and Ser-295 by CaMK1.|||Regulates clathrin-mediated receptor endocytosis (By similarity). Plays a role in the process of neurogenesis (PubMed:10841580, PubMed:12410312, PubMed:15273690, PubMed:17174898). Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate (PubMed:15273690, PubMed:12410312). Not required for the proliferation of neural progenitor cells before the onset of neurogenesis (PubMed:15273690, PubMed:12410312). Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity (PubMed:17174898). May also mediate local repair of brain ventricular wall damage (PubMed:17174898).|||Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation (By similarity) Isoform 1 and isoform 2 are ubiquitinated by LNX leading to their subsequent proteasomal degradation. http://togogenome.org/gene/10090:Helt ^@ http://purl.uniprot.org/uniprot/Q7TS99 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HEY family.|||Death between 2 and 5 weeks of age. The mesencephalic GABAergic progenitors in these animals fail to develop into neurons.|||Expressed in heart and testis.|||Expressed in the progenitor domains for mesencephalic GABAergic neurons.|||Nucleus|||Self-associates. Interacts with HES5 and HEY2.|||Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGCG-3'. Required for the development of GABAergic neurons. http://togogenome.org/gene/10090:Foxj3 ^@ http://purl.uniprot.org/uniprot/Q8BUR3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Accumulates in the testis starting at postnatal day 3, and remains at a steady level from 1 to 3 weeks in age.|||Highly expressed in spermatogonia, spermatocytes, and round spermatids within the testis (at protein level).|||Increased markedly during skeletal muscle differentiation (at protein level).|||Nucleus|||Null mice have an abnormal skeletal muscle fiber type ratio in males as well as defects in muscle regeneration following injury (PubMed:19914232). Male germ-cell-specific conditional knockout results in complete male infertility, early loss of spermatogonia and meiotic arrest in spermatocytes (PubMed:27739607). Spermatocytes show significantly reduced expression meiotic arrest-related genes (PubMed:27739607).|||Transcriptional activator of MEF2C involved in the regulation of adult muscle fiber type identity and skeletal muscle regeneration (PubMed:19914232). Plays an important role in spermatogenesis (PubMed:27739607). Required for the survival of spermatogonia and participates in spermatocyte meiosis (PubMed:27739607). http://togogenome.org/gene/10090:Xkrx ^@ http://purl.uniprot.org/uniprot/Q5GH68 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the XK family.|||Membrane http://togogenome.org/gene/10090:Slc9a3 ^@ http://purl.uniprot.org/uniprot/G3X939 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Deficient mice have diarrhea associated with proximal tubular acidosis and hypotension. Males are infertile.|||Early endosome membrane|||Homodimer (By similarity). Found in the forms of complex and dynamic macromolecular complexes (By similarity). Binds NHERF1 and NHERF2 (By similarity). Interacts with CHP1; this interaction increases trafficking and activity of SLC9A3 at the plasma membrane (By similarity). Interacts with CHP2 and SHANK2. Interacts with PDZK1 (via C-terminal PDZ domain) (By similarity). Interacts with NHERF4 and interactions decrease in response to elevated calcium ion levels (By similarity). Interacts with AHCYL1; the interaction is required for SLC9A3 activity (By similarity). Interacts with EZR; interaction targets SLC9A3 to the apical membrane (By similarity). Interacts with SNX27 (via PDZ domains); directs SLC9A3 membrane insertion from early endosomes to the plasma membrane (By similarity).|||Phosphorylated by PKA, which inhibits activity. Phosphorylation at Ser-659 by SGK1 is associated with increased abundance at the cell membrane. Phosphorylation at Ser-714 by CSNK2A1 regulates SLC9A3 activity through the formation of multiple signaling complexes (By similarity).|||Plasma membrane Na(+)/H(+) antiporter. Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry, playing a key role in salt and fluid absorption and pH homeostasis (By similarity). Major apical Na(+)/H(+) exchanger in kidney and intestine playing an important role in renal and intestine Na(+) absorption and blood pressure regulation (PubMed:9662405).|||Recycling endosome membrane|||Seems to switch between active and inactive modes in response to various stimuli (By similarity). Activated directly or indirectly by membrane phosphatidylinositol (PIs) (By similarity). Regulated by a variety of auxiliary proteins, which facilitate the maturation, cell surface expression and function of the transporter. Inhibited specifically by the drug tenapanor (By similarity).|||The C-terminal intracellular domain is subject to extensive post-translational modifications and binding partner interactions which regulate transporter activity, scaffolding functions, downstream events and localization. http://togogenome.org/gene/10090:Hsph1 ^@ http://purl.uniprot.org/uniprot/Q61699 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (By similarity). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (PubMed:14644449, PubMed:15292236).|||Belongs to the heat shock protein 70 family.|||By heat shock.|||Cytoplasm|||Expressed in neurons in the cerebrum and Purkinje cells in the cerebellum (at protein level) (PubMed:16232202, PubMed:10865058). Expressed in testis and no expression or only low-level expression in liver, spleen, lung, and kidney (at protein level) (PubMed:16232202). Highly expressed in the brain and moderately expressed in lung, heart, thymus, spleen, liver, and small intestine (PubMed:8530361).|||Interacts with HSPA8/HSC70 (PubMed:15292236, PubMed:9675148). Interacts with HSPA1A (via NBD) and HSPA1B (via NBD) (By similarity).|||Nucleus|||Phosphorylation on Ser-509 may be important for regulation of the HSPA8/HSC70 chaperone activity.|||There is sufficient sequence similarity to other members of the heat shock protein 70 family that some polyclonal antibodies raised against the HSPH1 protein may recognize other epitopes and so expression studies should be interpreted with caution (Probable). Some papers report high level expression in testis (at protein level) (PubMed:16232202). However, others do not detect expression in testis (at transcript level) (PubMed:8530361).|||Up-regulated by stresses such as treatment with arsenite or amino acid analogs. http://togogenome.org/gene/10090:B4gat1 ^@ http://purl.uniprot.org/uniprot/Q8BWP8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 49 family.|||Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1) (PubMed:23217742, PubMed:25279699). Transfers a glucuronic acid (GlcA) residue onto a xylose (Xyl) acceptor to produce the glucuronyl-beta-1,4-xylose-beta disaccharide primer, which is further elongated by LARGE1, during synthesis of phosphorylated O-mannosyl glycan (PubMed:25279699). Phosphorylated O-mannosyl glycan is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:25279699). Required for axon guidance; via its function in O-mannosylation of alpha-dystroglycan (DAG1) (PubMed:23217742).|||Early embryonic lethality.|||Golgi apparatus membrane|||Interacts with LARGE1 and LARGE2. http://togogenome.org/gene/10090:Ankrd11 ^@ http://purl.uniprot.org/uniprot/E9Q4F7 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (PubMed:25556659). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (By similarity). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). May also regulate bone homeostasis (PubMed:17986521).|||Detected in the cerebral cortex from embryonic stage 11 dpc through to postnatal stage P3, where it is primarily expressed in neural precursors.|||Interacts with the PAS region of the p160 coactivators.|||Nucleus|||Subject to proteasomal degradation which is probably essential to regulate its activity. http://togogenome.org/gene/10090:Trib1 ^@ http://purl.uniprot.org/uniprot/Q8K4K4 ^@ Domain|||Function|||Similarity|||Subunit ^@ Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase (PubMed:23515163, PubMed:20410507). Promotes CEBPA degradation and inhibits its function (PubMed:20410507). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (PubMed:24003916, PubMed:23515163). Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1-dependent manner (PubMed:23515163). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.|||Monomer. Interacts (via protein kinase domain) with CEBPA. Interacts with COP1.|||The C-terminus (351-372) is required for interaction with COP1 (By similarity).|||The COP1-binding motif (355-360) is required for regulation activity (PubMed:24003916).|||The protein kinase active site is incompatible with ATP binding and is inactive (By similarity). http://togogenome.org/gene/10090:Nanos2 ^@ http://purl.uniprot.org/uniprot/I6ZHM2|||http://purl.uniprot.org/uniprot/P60322 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nanos family.|||Cytoplasm|||First detectable at 13.5 dpc in the male gonocytes, levels increase until about 16.5 dpc and then slightly decrease by 17.5 dpc (at protein level). Expression is maintained in all male gonocytes during embryogenesis, but becomes confined to a small population of the spermatogonia after birth.|||Interacts with CNOT1, CNOT3, CNOT6L, CNOT7 and CNOT9.|||Mice show a gradual loss of the germ cell population within a few cycles of spermatogenesis which is caused by the depletion of spermatogonial stem cells that produce differentiating spermatogenic cells.|||P-body|||Plays a key role in the sexual differentiation of germ cells by promoting the male fate but suppressing the female fate. Represses the female fate pathways by suppressing meiosis, which in turn results in the promotion of the male fate. Maintains the suppression of meiosis by preventing STRA8 expression, which is required for premeiotic DNA replication, after CYP26B1 is decreased. Regulates the localization of the CCR4-NOT deadenylation complex to P-bodies and plays a role in recruiting the complex to trigger the degradation of mRNAs involved in meiosis. Required for the maintenance of the spermatogonial stem cell population. Not essential for the assembly of P-bodies but is required for the maintenance of their normal state.|||Predominantly expressed in male germ cells. Expressed in self-renewing spermatogonial stem cells and developing gonads.|||The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. It is essential for the translation repression activity of the protein.|||perinuclear region http://togogenome.org/gene/10090:Atg2a ^@ http://purl.uniprot.org/uniprot/Q6P4T0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Mediates the intracellular lifestyle of Cryptococcus neoformans by supporting infection.|||Belongs to the ATG2 family.|||Endoplasmic reticulum membrane|||Interacts with ATG9A (via C-terminus). Interacts with TMEM41B. Interacts with VMP1.|||Lipid droplet|||Lipid transfer protein involved in autophagosome assembly. Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion. Binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, and extracts phospholipids from the membrane source and transfers them to ATG9 (ATG9A or ATG9B) to the IM for membrane expansion. Lipid transfer activity is enhanced by WIPI1 and WDR45/WIPI4, which promote ATG2A-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes. Also regulates lipid droplets morphology and distribution within the cell.|||Preautophagosomal structure membrane|||The chorein N-terminal domain mediates lipid transfer activity. http://togogenome.org/gene/10090:Or4k5 ^@ http://purl.uniprot.org/uniprot/Q8VET4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Virma ^@ http://purl.uniprot.org/uniprot/A2AIV2|||http://purl.uniprot.org/uniprot/E9PZY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs in the 3'-UTR near the stop codon: recruits the catalytic core components METTL3 and METTL14, thereby guiding m6A methylation at specific sites. Required for mRNA polyadenylation via its role in selective m6A methylation: m6A methylation of mRNAs in the 3'-UTR near the stop codon correlating with alternative polyadenylation (APA).|||Belongs to the vir family.|||Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716). Interacts with WTAP (By similarity). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (By similarity). Interacts with NUDT21 and CPSF6 (By similarity).|||Cytoplasm|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Hey2 ^@ http://purl.uniprot.org/uniprot/Q9QUS4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HEY family.|||By activation of the Notch signaling pathway.|||Expressed in the developing somites and the ventricles of the heart. Expressed in the otic vesicles between 8.5 dpc and 10.5 dpc. Expressed in the myocardium of the ventricles at 9.5 dpc and in the atrioventricular cushions from 9.5 to 12.5 dpc. At 10.5 dpc, strongly expressed in the spinal nerves, the cranial ganglia and the telencephalon. At 11.5 dpc, expressed in the craniofacial region of the distal part of the maxillary arch, along the rostral mandibular arch and surrounding the lateral nasal processes. Expressed in the midbrain-hindbrain boundary and the posterior edge of the hand- and foot-paddle. Expressed in the mediodorsal region of the telencephalon and the ventricular zone of the ventral spinal cord at 12 dpc, then in the ventral region of the telencephalon and the cortical plate at 15 dpc. Expression in the heart is limited to the compact myocardial layer at 17.5 dpc. Also expressed in the developing retina up to P5, at which point expression decreases.|||Highly expressed in the aorta, lower expression detected in the heart, brain, kidney, lung, muscle, ovary and testis.|||May self-associate (By similarity). Interacts with ARNT (By similarity). Interacts with GATA4, GATA6, HES1 and HEYL. Interacts with HDAC1, NCOR1 and SIN3A.|||Mice display a spectrum of cardiac malformations including ventricular septal defects, tetralogy of Fallot and tricuspid atresia. The penetrance of the cardiac malformation phenotype varies according to the strain, suggesting the presence of modifier genes.|||Nucleus|||Transcriptional repressor which functions as a downstream effector of Notch signaling in cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. May be required in conjunction with HEY1 to specify arterial cell fate or identity. Promotes maintenance of neuronal precursor cells and glial versus neuronal fate specification. Binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6 and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3. http://togogenome.org/gene/10090:Papolg ^@ http://purl.uniprot.org/uniprot/Q6PCL9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the poly(A) polymerase family.|||Binds 2 magnesium ions. Also active with manganese.|||Nucleus|||Responsible for the post-transcriptional adenylation of the 3'-terminal of mRNA precursors and several small RNAs including signal recognition particle (SRP) RNA, nuclear 7SK RNA, U2 small nuclear RNA, and ribosomal 5S RNA. http://togogenome.org/gene/10090:Pik3r3 ^@ http://purl.uniprot.org/uniprot/Q3UXE9|||http://purl.uniprot.org/uniprot/Q64143 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PI3K p85 subunit family.|||Binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1.|||Heterodimer of a regulatory subunit PIK3R3 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL (By similarity).|||Highest levels in brain and testis. Lower levels in adipose tissue, kidney, heart, lung and skeletal muscle. Barely detectable in liver and spleen. http://togogenome.org/gene/10090:Commd4 ^@ http://purl.uniprot.org/uniprot/Q9CQ02 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL2, CUL3, CUL4A, CUL5, CUL7.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Down-regulates activation of NF-kappa-B.|||Nucleus http://togogenome.org/gene/10090:Yy1 ^@ http://purl.uniprot.org/uniprot/Q00899 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 7.5 dpc, highly expressed in the ectoplacental cone and, at lower levels, in the embryonic and extraembryonic ectoderm. At 14.5 dpc, highly expressed in placenta and yolk sac, and, at lower levels, in brain and heart.|||Belongs to the YY transcription factor family.|||Cytoplasm|||Expressed in ovary and, at lower levels, in testis.|||Interacts with YAF2 through the region encompassing the first and second zinc fingers. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80. Interacts with EED and EZH2; the interactions are indicative for an association with the PRC2/EED-EZH2 complex (By similarity). Found in a complex with SMAD1 and SMAD4 (PubMed:15329343). Interacts with SFMBT2 (PubMed:18024232). Found in a complex with YY1, SIN3A and HDAC1 (PubMed:21454521).|||Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site. Binds to the consensus sequence 5'-CCGCCATNTT-3'; some genes have been shown to contain a longer binding motif allowing enhanced binding; the initial CG dinucleotide can be methylated greatly reducing the binding affinity. The effect on transcription regulation is depending upon the context in which it binds and diverse mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes. Its activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression. Binds to the upstream conserved region (UCR) (5'-CGCCATTTT-3') of Moloney murine leukemia virus (MuLV). Acts synergistically with the SMAD1 and SMAD4 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343). Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (PubMed:15329343). Proposed to recruit the PRC2/EED-EZH2 complex to target genes that are transcriptional repressed. Involved in DNA repair. In vitro, binds to DNA recombination intermediate structures (Holliday junctions). Involved in spermatogenesis and may play a role in meiotic DNA double-strand break repair. Plays a role in regulating enhancer activation (By similarity).|||Nucleus|||Nucleus matrix|||Phosphorylation at Ser-120 by CK2 prevents proteolytic cleavage by caspase-7 (CASP7) during apoptosis.|||Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair; proposed to target the INO80 complex to YY1-responsive elements.|||Proteolytically cleaved by caspase-7 (CASP7) in response to apoptosis. Phosphorylation at Ser-120 protects against proteolytic cleavage.|||Spermatocytes have a significant decrease in the global level of the heterochromatin markers and increase in the chromosomal double-strand break (DSB) signals at the leptotene/zygotene stages.|||Transiently poly-ADP-ribosylated by PARP1 upon DNA damage, with the effect of decreasing affinity of YY1 to its cognate DNA binding sites.|||Ubiquitinated. http://togogenome.org/gene/10090:Ppif ^@ http://purl.uniprot.org/uniprot/Q99KR7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated at Lys-166; deacetylated at Lys-166 by SIRT3.|||Associates with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase; the association is increased by inorganic phosphate (Pi) and decreased by cyclosporin A (CsA) (PubMed:19801635). Interacts with ATP5F1B; ATP5PD and ATP5PO (PubMed:21281446). Interacts with SLC25A3; the interaction is impaired by CsA (By similarity). Interacts with BCL2; the interaction is impaired by CsA. Interacts with TP53; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by CsA (PubMed:22726440). Interacts with C1QBP (PubMed:20950273). Interacts with MCUR1 (By similarity). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (By similarity). Interacts with SPG7 (By similarity).|||Belongs to the cyclophilin-type PPIase family.|||Binds cyclosporin A (CsA). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP.|||Mice are developmentally normal and show no apparent anomalies (PubMed:15800626, PubMed:15800627, PubMed:16103352). Mitochondria do not undergo cyclosporin A-sensitive mitochondrial permeability transtition (PubMed:15800626, PubMed:15800627, PubMed:16103352). Cells show resistance to necrotic cell death induced by reactive oxygen species and Ca(2+) overload, and animals show a high level of resistance to ischaemia/reperfusion-induced cardiac injury (PubMed:15800626, PubMed:15800627, PubMed:16103352). Mice show a dramatic reduction in brain infarct size after acute middle cerebral artery occlusion and reperfusion (PubMed:15800626, PubMed:15800627, PubMed:16103352). Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca(2+)-induced mitochondrial permeability transition pore (mPTP) formation (PubMed:31489369).|||Mitochondrion matrix|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding (By similarity). Involved in regulation of the mitochondrial permeability transition pore (mPTP) (PubMed:15800626, PubMed:15800627, PubMed:16103352, PubMed:18684715, PubMed:31489369). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated (PubMed:15800626, PubMed:15800627, PubMed:16103352, PubMed:18684715, PubMed:31489369). In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis (PubMed:22726440). Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels (PubMed:19801635, PubMed:21281446). Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis (By similarity). http://togogenome.org/gene/10090:Eny2 ^@ http://purl.uniprot.org/uniprot/Q9JIX0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ENY2 family.|||Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least ENY2, the isoform GANP of the MCM3AP gene, PCID2, SEM1, and either centrin CETN2 or CETN3. TREX-2 contains 2 ENY2 chains. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153 (By similarity). Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H, TAF10, TRRAP and USP22. Within the SAGA complex, ENY2, ATXN7, ATXN7L3, and USP22 form an additional subcomplex of SAGA called the DUB module (deubiquitination module). Interacts with the RNA polymerase II subunit POLR2A (By similarity). Interacts with ATXN7L3B (By similarity).|||Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes. The transcription regulatory histone acetylation (HAT) complex SAGA is a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Or7h8 ^@ http://purl.uniprot.org/uniprot/Q7TRF0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem191 ^@ http://purl.uniprot.org/uniprot/Q9JJB1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM191 family.|||Membrane http://togogenome.org/gene/10090:Sfrp1 ^@ http://purl.uniprot.org/uniprot/Q8C4U3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the secreted frizzled-related protein (sFRP) family.|||Highly expressed in kidney and embryonic heart. Also highly expressed in the eye, where it is principally localized to the ciliary body and the lens epithelium. Weaker expression in heart, lung and brain. In the brain, is expressed exclusively in the choroid plexus.|||In the developing kidney expressed at 13.5 dpc in the periphery of the metanophros and surrounding the uretic and nephrogenic tubules. At 14.5 dpc, expression decreases in the outer cortical cells and becomes visible in the tubular parts of the nephron. From 15.5 dpc, highly expressed in the future loops of Henle. In the developing CNS, expression located to the forebrain and hindbrain. At 8.0 dpc, expressed in the future forebrain and in the ventral portion of the presumptive hindbrain. At 8.5 dpc, expression is maintained in these tissues with a strong signal in rhombomere 4. Until 11.5 dpc, expression continues in the hindbrain with additional expression at 9.5 dpc and 10.5 dpc, in the nasal and epibranchial placodes. In the forebrain, initial expression is found in the proencephalon of the forebrain, and then strong expression in the telencephalic vesicle up to 15.5 dpc. Expression is then found in specific cell populations throughout the brain. In the developing eye, expression, by 10.5 dpc, is confined to ectodermal cells overlying the dorsal part of the optic cup. In later stages, expression limited to the lens fiber cells and the future pigmented retina. By 15.5 dpc, expression is confined to the anterior part of the lens. During limb development, barely expressed until later stages, when it is found in the distal part of the separating phalanges. In other developing structures, expressed in nasal placodes at 9.5 dpc, in medial nasal processes at 10.5 dpc and then in the anterior portion of the invaginating olfactory epithelium. At 15.5 dpc, expressed on the basal side of the nasal epithelium. Expressed in the mandibular molar tooth mesenchyme at 13.5 dpc (PubMed:27713059). Expressed in developing teeth, with the highest levels at 15.5 dpc and 16.5 dpc in the mesenchyme and the dental epithelium of the developing molars. As well, expressed in the ventral body wall, in the mesenchyme derived adrenal cortex, the cochlear epithelium and the branching epithelium of the salivary gland. In the developing heart, weakly expressed from 8.5 dpc in the tubular heart endocardium and myocardium. From 8.5 dpc to 12.5 dpc expressed in cardiomyocytes. At 9.5 dpc, expression found in the common ventricular and atrial chamber of the developing heart, in the aortic sac and in the sinus venosus. High expression found from 11.5 dpc-12.5 dpc, in the trabeculated wall of the ventricular chamber together with the wall of the atrial chamber. Expression also found in the muscular part of the interventricular septum. From 9.5 dpc-11.5 dpc expression in the visceral yolk sac confined to the inner lining endothelial cell layer. Expression in the developing heart decreases after 14.5 dpc.|||Interacts with WNT8, WNT1, WNT2, WNT4 and FRZD6 (By similarity). Interacts with MYOC.|||Secreted|||Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP1 decreases intracellular beta-catenin levels (By similarity). Has antiproliferative effects on vascular cells, in vitro and in vivo, and can induce, in vivo, an angiogenic response. In vascular cell cycle, delays the G1 phase and entry into the S phase. In kidney development, inhibits tubule formation and bud growth in metanephroi (By similarity). Inhibits WNT1/WNT4-mediated TCF-dependent transcription (By similarity).|||The FZ domain is involved in binding with Wnt ligands. http://togogenome.org/gene/10090:Pramel22 ^@ http://purl.uniprot.org/uniprot/A2AGW6 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Ttc17 ^@ http://purl.uniprot.org/uniprot/E9PVB5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TTC17 family.|||Cell membrane|||Cytoplasm|||Interacts with CATIP.|||Plays a role in primary ciliogenesis by modulating actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Ogdh ^@ http://purl.uniprot.org/uniprot/Q60597|||http://purl.uniprot.org/uniprot/Z4YJV4 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC). Participates in the first step, rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) catalyzed by the whole OGDHC. Catalyzes the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST). Plays a key role in the Krebs (citric acid) cycle, which is a common pathway for oxidation of fuel molecules, including carbohydrates, fatty acids, and amino acids. Can catalyze the decarboxylation of 2-oxoadipate in vitro, but at a much lower rate than 2-oxoglutarate. Mainly active in the mitochondrion. A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A.|||Belongs to the alpha-ketoglutarate dehydrogenase family.|||Calcium ions and ADP stimulate, whereas ATP and NADH reduce catalytic activity.|||Mitochondrion|||Nucleus|||The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A.|||The mitochondrial 2-oxoglutarate and 2-oxoadipate dehydrogenase complexes (OGDHC and OADHC, respectively) share their E2 (DLST) and E3 (dihydrolipoyl dehydrogenase or DLD) components, but the E1 component is specific to each complex (E1o and E1a (DHTK1), respectively). http://togogenome.org/gene/10090:Elavl3 ^@ http://purl.uniprot.org/uniprot/Q60900 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RRM elav family.|||Brain specific (PubMed:9016658). Expressed in the hippocampus with expression in CA1, CA3 and dentate gyrus (PubMed:11573004).|||Interacts with MAP1B light chain LC1.|||RNA-binding protein that binds to AU-rich element (ARE) sequences of target mRNAs, including VEGF mRNA (PubMed:10734193, PubMed:9016658). May also bind poly-A tracts via RRM 3 (PubMed:9016658). May be involved in neuronal differentiation and maintenance (PubMed:9016658). Plays a role in the stabilization of GAP43 mRNA and in spatial learning (PubMed:11573004).|||RNAi-mediated knockdown results in reduced Gap43 mRNA levels and impaired learning behavior in radial arm maze training.|||RRM 1 and RRM 2 bind cooperatively to AU-rich sequences in target mRNAs. RRM 3 binds to poly-A mRNA sequences.|||Up-regulated after spatial learning in radial arm maze experiments and in Morris water maze experiments. http://togogenome.org/gene/10090:Aplp2 ^@ http://purl.uniprot.org/uniprot/Q06335|||http://purl.uniprot.org/uniprot/Q60709|||http://purl.uniprot.org/uniprot/Q64348 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APP family.|||Cell membrane|||Interacts with CPEB1. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via cytoplasmic domain) with APBB2/FE65L (By similarity). Interacts (via intracellular domain) with APBB3/FE65L2 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play a role in the regulation of hemostasis. The soluble form may have inhibitory properties towards coagulation factors. May interact with cellular G-protein signaling pathways. May bind to the DNA 5'-GTCACATG-3'(CDEI box). Inhibits trypsin, chymotrypsin, plasmin, factor XIA and plasma and glandular kallikrein (By similarity). Modulates the Cu/Zn nitric oxide-catalyzed autodegradation of GPC1 heparan sulfate side chains in fibroblasts.|||Membrane|||Nucleus http://togogenome.org/gene/10090:Or51a25 ^@ http://purl.uniprot.org/uniprot/Q8VH14 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adgrb1 ^@ http://purl.uniprot.org/uniprot/Q3UHD1 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Cell membrane|||In brain, widespread expression in all neuropil-rich zones including spinal cord gray matter, cerebellar molecular layer, cerebral cortex, thalamic nuclei and basal ganglia with no expression in white matter (at protein level) (PubMed:20888903). In the cerebellar molecular layer, highly expressed in interneuron processes whereas Purkinje cells and their dendrites show weaker expression (at protein level) (PubMed:20888903). In the olfactory bulb, highly expressed in glomeruli (at protein level) (PubMed:20888903). In the retina, highly concentrated in the outer and inner plexiform layers (at protein level) (PubMed:20888903). Expressed in brain (PubMed:11245925). Enriched in hippocampus and cortex (PubMed:23595754). Also detected in other tissues including bone marrow and spleen (PubMed:17960134).|||Inhibits angiogenesis in a CD36-dependent manner.|||Inhibits angiogenesis.|||Interacts with ELMO1 and DOCK1 (PubMed:17960134). When bound to ELMO1 and DOCK1, acts as a module to promote apoptotic cell engulfment (PubMed:17960134). Interacts with MDM2; the interaction results in inhibition of MDM2-mediated ubiquitination and degradation of DLG4/PSD95 (PubMed:25751059). Interacts with PARD3 and TIAM1; the interaction is required for correct dendritic localization of PARD3 and TIAM1 and for dendritic spine formation (By similarity). Interacts with MAGI1, MAGI3 and BAIAP2 (By similarity). Interacts with PHYHIP (PubMed:11245925). Interacts with DLG4 (via PDZ domain) (By similarity). Vasculostatin-120: Interacts with CD36 (By similarity). Vasculostatin-120: Interacts with ARRB2 (By similarity). Interacts with BAIAP3; this interaction is direct (By similarity).|||Observed very weakly in the kidney, skeletal muscle, skin, stomach, thymus and brain from embryonic day 18. By neonatal day 1, the expression is targeted only to the brain.|||Phosphatidylserine receptor which enhances the engulfment of apoptotic cells (PubMed:17960134). Also mediates the binding and engulfment of Gram-negative bacteria (PubMed:21245295, PubMed:26838550, PubMed:26838550). Stimulates production of reactive oxygen species by macrophages in response to Gram-negative bacteria, resulting in enhanced microbicidal macrophage activity (By similarity). In the gastric mucosa, required for recognition and engulfment of apoptotic gastric epithelial cells (By similarity). Promotes myoblast fusion (PubMed:23615608). Activates the Rho pathway in a G-protein-dependent manner (By similarity). Inhibits MDM2-mediated ubiquitination and degradation of DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity (PubMed:25751059). Required for the formation of dendritic spines by ensuring the correct localization of PARD3 and TIAM1 (By similarity). Potent inhibitor of angiogenesis in brain and may play a significant role as a mediator of the p53/TP53 signal in suppression of glioblastoma (By similarity).|||Postsynaptic density|||Proteolytically cleaved to produce vasculostatin-40 and vasculostatin-120. Vasculostatin-40 is the major form and is produced through proteolytic cleavage by MMP14 between residues 321 and 329 with cleavage likely to be between Ser-326 and Leu-327.|||Secreted|||The TSP type-1 repeats in the extracellular domain mediate binding to phosphatidylserine (PubMed:17960134). They are also required for bacterial recognition and binding to bacterial outer membrane lipopolysaccharide (PubMed:21245295).|||Ubiquitinated.|||Viable and fertile with normal brain anatomy but mutants display severe deficits in hippocampus-dependent spatial learning and memory that are accompanied by enhanced long-term potentiation, impaired long-term depression, a thinning of the postsynaptic density at hippocampal synapses, reduced protein levels of Dlg4 and increased Dlg4 polyubiquitination (PubMed:25751059). Smaller myofibers than wild-type animals and impaired muscle regeneration after injury (PubMed:23615608). Impaired bacterial clearance following E.coli infection (PubMed:26838550). RNAi-mediated knockdown in embryos results in greatly reduced dendritic spine density and small but significant increases in spine length and decreases in spine diameter (PubMed:23595754).|||dendritic spine|||focal adhesion|||phagocytic cup http://togogenome.org/gene/10090:Dipk1b ^@ http://purl.uniprot.org/uniprot/Q99ML4 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Among the many cysteines in the lumenal domain, most are probably involved in disulfide bonds.|||Belongs to the DIPK family.|||Endoplasmic reticulum membrane|||Expressed in kidney, testis, lung, heart, stomach, intestine, pancreas, liver and salivary gland. Strongly expressed in acute pancreatitis, brain, and in peripheral endothelial cells. http://togogenome.org/gene/10090:Csta3 ^@ http://purl.uniprot.org/uniprot/Q6IE28 ^@ Similarity ^@ Belongs to the cystatin family. http://togogenome.org/gene/10090:Bglap ^@ http://purl.uniprot.org/uniprot/P86546 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the osteocalcin/matrix Gla protein family.|||Bone.|||Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (PubMed:29148101).|||Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX (By similarity). These residues are essential for the binding of calcium (By similarity). Carboxylated in a Ptprv/Esp-dependent process (PubMed:17693256, PubMed:20655470, PubMed:20655471). Decarboxylation promotes the hormone activity (PubMed:17693256, PubMed:20655470, PubMed:20655471, PubMed:21333348, PubMed:24074871).|||Mice lacking Bglap and Bglap2 show increased bone formation, characterized by higher bone mass and bones of improved functional quality (PubMed:8684484). Mice lacking Bglap and Bglap2 also display reduced male fertility due to decreased testosterone production in the testes (PubMed:21333348). Mice lacking Bglap and Bglap2 are passive and show greater anxiety-like behaviors due to impaired synthesis of neurotransmitters (PubMed:24074871).|||Secreted|||The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein: it acts as a negative regulator of bone formation and is required to limit bone formation without impairing bone resorption or mineralization (PubMed:8684484). The carboxylated form binds strongly to apatite and calcium (PubMed:17693256).|||The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development (PubMed:17693256, PubMed:20655470, PubMed:20655471, PubMed:21333348, PubMed:24074871). Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure (PubMed:17693256, PubMed:20655470, PubMed:20655471). Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner (PubMed:21333348). Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA) (PubMed:24074871, PubMed:28851741). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development (PubMed:24074871). http://togogenome.org/gene/10090:Vmn2r7 ^@ http://purl.uniprot.org/uniprot/E9PZ74 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbm8a ^@ http://purl.uniprot.org/uniprot/Q9CWZ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RBM8A family.|||Cytoplasm|||Heterodimer with either MAGOH or MAGOHB. Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A. Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs. Part of a complex that contains the EJC core components CASC3, EIF4A3, MAGOH and RBM8A plus proteins involved in nonsense-mediated mRNA decay, such as UPF1, UPF2, UPF3A and UPF3B. Found in a post-splicing complex with NXF1, MAGOH, UPF1, UPF2, UPF3A, UPF3B and RNPS1. Interacts with DDX39B, MAGOH, DPH1, UPF3B, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with IPO13; the interaction mediates the nuclear import of the MAGOH-RBM8A heterodimer. Identified in the spliceosome C complex. Associates with polysomes.|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the spliceosome (By similarity). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs (By similarity). http://togogenome.org/gene/10090:Dennd6b ^@ http://purl.uniprot.org/uniprot/Q9D9V7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DENND6 family.|||Cytoplasm|||Guanine nucleotide exchange factor (GEF) for RAB14. Also has some, lesser GEF activity towards RAB35 (By similarity).|||Identified as having similarity to the core DENN family and referred to as DENN6B. Prediction methods do not indicate a DENN domain for this sequence and, the exact role of the DENN or this DENN-like domain in GEF activity needs to be clarified.|||Recycling endosome http://togogenome.org/gene/10090:Hrob ^@ http://purl.uniprot.org/uniprot/Q32P12 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||DNA-binding protein involved in homologous recombination that acts by recruiting the MCM8-MCM9 helicase complex to sites of DNA damage to promote DNA repair synthesis.|||Deficient female and male mice exhibit infertility associated with impaired ovarian development and arrested male meiosis.|||Interacts with MCM8; this interaction is necessary for MCM8-MCM9 helicase complex recruitment to DNA damage sites (By similarity). Interacts with RPA1; this interaction associates HROB with the RPA complex (PubMed:31467087).|||Nucleus http://togogenome.org/gene/10090:Bud31 ^@ http://purl.uniprot.org/uniprot/Q6PGH1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BUD31 (G10) family.|||Contains a short sequence motif (Phe-Xaa-Xaa-Phe-Tyr) that can bind to AR and may modulate AR activity.|||Identified in the spliceosome C complex. May interact with AR.|||Involved in the pre-mRNA splicing process. May play a role as regulator of AR transcriptional activity; may increase AR transcriptional activity.|||Nucleus http://togogenome.org/gene/10090:Ric3 ^@ http://purl.uniprot.org/uniprot/D3YTZ9|||http://purl.uniprot.org/uniprot/Q8BPM6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ric-3 family.|||Endoplasmic reticulum membrane|||Expressed in brain, with highest levels in hippocampus, cerebellum and superior colliculus.|||Molecular chaperone which promotes the proper subunit assembly and surface trafficking of alpha-7 (CHRNA7) nicotinic acetylcholine receptor (PubMed:19812337, PubMed:32204458). Promotes the proper subunit assembly and cell surface expression of alpha-8 (CHRNA8) nicotinic acetylcholine receptor (By similarity). May also promote functional expression of homomeric serotoninergic 5-HT3 receptors, and of heteromeric acetylcholine receptors alpha-3/beta-2, alpha-3/beta-4, alpha-4/beta-2 and alpha-4/beta-4 (By similarity).|||Monomer and homodimer. Interacts with CHRNA7, CHRNA3, CHRNA4, CHRNB2, CHRNB4 and HTR3A (By similarity).|||The coiled-coil domain mediates transient homodimerization with other acetylcholine receptor-bound RIC3 molecules, promoting stepwise ACHR homomeric assembly at the membrane. http://togogenome.org/gene/10090:B3gnt7 ^@ http://purl.uniprot.org/uniprot/Q8K0J2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Golgi apparatus membrane|||Mutant mice are born at the expected Mendelian rate and have normal developmental and reproductive potential. They develop an abnormal corneal ultrastructure characterized by a lack of keratan sulfate proteoglycans that appears to be compensated by increased amount of elongated, branched electron dense chondroitin sulfate/dermatan sulfate proteoglycan filaments.|||N-acetyl glucosamine (GlcNAc) transferase that catalyzes the transfer of GlcNAc via a beta1->3 linkage from UDP-GlcNAc to the non-reducing terminal galactose (Gal) in the linearly growing chain of N-and O-linked keratan sulfate proteoglycans. Cooperates with B4GALT4 galactosyltransferase and CHST6 and CHST1 sulfotransferases to construct and elongate mono- and disulfated disaccharide units [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] and [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer (By similarity). Involved in biosynthesis of N-linked keratan sulfate proteoglycans in cornea, with an impact on proteoglycan fibril organization and corneal transparency (PubMed:29625490). May play a role in the maintenance of tissue architecture by suppressing cellular motility and invasion (PubMed:12061784).|||Strongly expressed in placenta and colon. Moderately expressed in lung, stomach, small intestine and kidney. Very weakly expressed in cerebrum, cerebellum, heart and testis. http://togogenome.org/gene/10090:Rgs12 ^@ http://purl.uniprot.org/uniprot/D3Z0G5|||http://purl.uniprot.org/uniprot/E9Q1K7|||http://purl.uniprot.org/uniprot/E9Q652|||http://purl.uniprot.org/uniprot/Q8CGE9|||http://purl.uniprot.org/uniprot/Q9D677 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain.|||Expressed in germinal vesicle oocyte, metaphase II oocyte and blastocyst (at protein level). Expressed in oocyte.|||Interacts with GNAI1, GNAI2 and GNAI3; the interactions are GDP-dependent.|||Nucleus|||Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form.|||Synapse|||The GoLoco domain is necessary for interaction with GNAI1, GNAI2 and GNAI3.|||dendrite http://togogenome.org/gene/10090:Sel1l ^@ http://purl.uniprot.org/uniprot/Q9Z2G6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sel-1 family.|||Endoplasmic reticulum membrane|||First detected at 12.5 dpc in a small number of pancreas epithelial cells. Highly expressed in embryonic pancreas epithelium at later stages of embryonic development.|||Gene disruption after residue 465 and replacement of the C-terminus with a beta-galactosidase-neomycin reporter gene construct leads to complete embryonic lethality; most die before 13.5 dpc. Only 5% of the embryos are viable at 15.5 dpc. Mutant embryos display defects in the differentiation of the pancreas epithelium. The defects in pancreas differentiation can be alleviated by pharmacological inhibition of Notch signaling (in vitro).|||Highly expressed in pancreas, white adipose tissue, liver and spleen (at protein level) (PubMed:25066055, PubMed:24453213). Detected in heart, brain, spleen, lung, liver, kidney and testis (PubMed:9858735).|||Homodimer and homooligomer (PubMed:27064360). May form a complex with ERLEC1, HSPA5, OS9, and SYVN1 (By similarity). Interacts with FOXRED2 and EDEM1 (By similarity). Interacts with LPL and LMF1; may stabilize the complex formed by LPL and LMF1 and thereby promote the export of LPL dimers (PubMed:25066055). Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1 (By similarity). SYNV1 assembles with SEL1L and FAM8A1 through its transmembrane domains, but interaction with its cytoplasmic domain is required to confer stability to FAM8A1 and enhance recruitment of HERPUD1 (By similarity). The interaction with SYNV1/HRD1 is direct (PubMed:25066055, PubMed:27064360).|||N-glycosylated.|||Plays a role in the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:25066055, PubMed:24453213). Enhances SYVN1 stability (PubMed:24453213). Plays a role in LPL maturation and secretion (PubMed:25066055). Required for normal differentiation of the pancreas epithelium, and for normal exocrine function and survival of pancreatic cells (PubMed:20170518, PubMed:24453213). May play a role in Notch signaling (PubMed:20170518).|||Taxomifen-inducible gene disruption in adult mice leads to premature death within 3 weeks after the onset of taxomifen treatment. Mice progressively loose weight and become moribund despite increased food intake and normal blood glucose levels, suggesting nutrient maladsorption. After eight days of treatment, the pancreas was diffusely dark red and soft, suggesting severe pancreas atrophy. Still, the endocrine parts of the pancreas were not affected. Pancreas weight was about half of that of wild-type, the size of secretory zymogen granules was reduced and pancreatic lipase and alpha-amylase levels were strongly reduced. Besides, the morphology of the endoplasmic reticulum in pancreas acinar cells was abnormal, with swollen and fragmented cisternae. Likewise, SYVN1 protein levels are decreased, while those of other ERAD markers are increased (PubMed:24453213). Adipocyte-specific gene disruption does not give rise to any obvious phenotype when mice are kept on a low-fat diet. Mutant mice are resistant to diet-induced obesity when kept on a high-fat diet, in spite of normal food intake and physical activity. Mutant mice show dramatically reduced accumulation of fat mass relative to wild-type, while lean mass is not affected. Intriguingly, mutant mice display enlarged livers that develop steatosis and increased triglyceride levels. Mutant mice display increased fasting serum triglyceride and insulin levels. Likewise, mutant mice display hypertriglyceridemia after feeding, especially on a high-fat diet. In spite of increased cellular LPL levels, LPL secretion is reduced by 80 to 90% (PubMed:25066055). http://togogenome.org/gene/10090:Elovl2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1P7|||http://purl.uniprot.org/uniprot/Q543J1|||http://purl.uniprot.org/uniprot/Q9JLJ4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ELO family. ELOVL2 subfamily.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. Condensing enzyme that catalyzes the synthesis of polyunsaturated very long chain fatty acid (C20- and C22-PUFA). May participate to the production of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that catalyzes the synthesis of polyunsaturated very long chain fatty acid (C20- and C22-PUFA), acting specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. May participate in the production of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Essential for the formation of C24:5(n-6) up to C30:5(n-6) PUFAs in testis, these fatty acids being indispensable for normal spermatogenesis and fertility.|||Endoplasmic reticulum membrane|||Highly expressed in testis, lower level in liver. Weakly expressed in white adipose tissue, brain and kidney.|||Membrane|||The C-terminal di-lysine motif may confer endoplasmic reticulum localization. http://togogenome.org/gene/10090:Rcor1 ^@ http://purl.uniprot.org/uniprot/Q8CFE3 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At embryonic day 8.5, it is highly expressed in the head mesenchyme, but neither in the somites nor in the presomitic mesoderm. By day 11.5 it is expressed fairly ubiquitously throughout the embryo.|||Belongs to the CoREST family.|||Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with REST. Interacts with the SMARCE1/BAF57, suggesting that the BHC complex may recruit the ATP-dependent chromatin-remodeling SWI-SNF complex (By similarity). Interacts directly with GFI1 and GFI1B in a RCOR/GFI/KDM1A/HDAC complex. Interacts with INMS1. Interacts with SOX2 (PubMed:30442713).|||Down-regulated by the transcriptional repressor ZEB1 during NEUROD2-induced neurogenesis.|||Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it serves as a molecular beacon for the recruitment of molecular machinery, including MeCP2 and SUV39H1, that imposes silencing across a chromosomal interval. Plays a central role in demethylation of Lys-4 of histone H3 by promoting demethylase activity of KDM1A on core histones and nucleosomal substrates. It also protects KDM1A from the proteasome. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation.|||Expressed in the external germinal layer (EGL) and internal granular layer (IGL) of the cerebellum and in Purkinje cells (at protein level).|||Nucleus|||The SANT domains may bridge the nucleosomal substrates and the demethylase KDM1A. http://togogenome.org/gene/10090:Gm10665 ^@ http://purl.uniprot.org/uniprot/K7N6B7 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Cln3 ^@ http://purl.uniprot.org/uniprot/Q61124|||http://purl.uniprot.org/uniprot/Q6PAH4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the battenin family.|||Early endosome membrane|||Embryos are viable and fertile and by 12 months of age do not exhibit obvious clinical signs but have significantly shortened life spans (PubMed:10527801, PubMed:17962032). Mice show elevation of lysosomal enzymes in brain and accumulation of autofluorescent storage material in neurons, retina and other cell types that increases with age (PubMed:10527801, PubMed:10440905, PubMed:17962032, PubMed:17855597). They also show neuropathological abnormalities with loss of certain cortical interneurons and hypertrophy of many interneuron populations in the hippocampus (PubMed:10527801). Moreover display progressive neurological deficits, including impaired motor function, decreased overall activity, acquisition of resting tremors, and increased susceptibility to pentilentetrazole-induced seizures (PubMed:17855597). Mice exhibit progressively impaired inner retinal function, altered pupillary light reflexes, losses of inner retinal neurons, and reduced brain mass. Mice show behavioral changes including reduced spontaneous activity levels and impaired learning and memory (PubMed:17962032). Cln3 hypomorphic mutant mice, harboring the ~1 kb common juvenile neuronal ceroid lipofuscinosis (JNCL) mutation, express multiple Cln3 mRNA splice variants and mutant battenin protein. Homozygous Cln3 mice exhibit a progressive JNCL-like disease, with perinatal onset of subunit c of ATP synthasedeposition in many cell types and later onset of neuronal dysfunction and behavioral deficits (PubMed:12374761). Can serve as an animal model for studying neuronal ceroid lipofuscinosis 3/Batten disease (PubMed:10527801, PubMed:10440905, PubMed:17962032, PubMed:12374761).|||Expressed throughout the brain, such as, in the cerebral cortex, hippocampus, cerebellum and several different cerebral nuclei (at protein level). In the cerebral cortex, expressed in all cortical layers. In the hippocampus, expressed in the granule cells in the dentate gyrus and the pyramidal cells of the hippocampus proper. In the cerebellum expressed in the granular and molecular layers, and in the Purkinje cell layer.|||Expression is osmoregulated in renal medullary cells.|||Farnesylation is important for trafficking to lysosomes.|||Highly glycosylated.|||Homooligomer (PubMed:11590129). Interacts with DCTN1, KIF3A, RAB7A and RILP (By similarity). Interacts with CLN5 (PubMed:19941651). Interacts with KCNIP3 (PubMed:17189291).|||Late endosome|||Late endosome membrane|||Lysosome|||Lysosome membrane|||Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocytosis, autophagy, transport of proteins and lipids from the TGN, apoptosis and synaptic transmission (PubMed:10191118, PubMed:24227717, PubMed:15588329, PubMed:29780879, PubMed:26450516, PubMed:16714284, PubMed:25878248, PubMed:17855597). Facilitates the proteins transport from trans-Golgi network (TGN)-to other membrane compartments such as transport of microdomain-associated proteins to the plasma membrane, IGF2R transport to the lysosome where it regulates the CTSD release leading to regulation of CTSD maturation and thereby APP intracellular processing (PubMed:24227717). Moreover regulates CTSD activity in response to osmotic stress (By similarity). Also binds galactosylceramide and transports it from the trans Golgi to the rafts, which may have immediate and downstream effects on cell survival by modulating ceramide synthesis (PubMed:10191118). At the plasma membrane, regulates actin-dependent events including filopodia formation, cell migration, and pinocytosis through ARF1-CDC42 pathway and also the cytoskeleton organization through interaction with MYH10 and fodrin leading to the regulation of the plasma membrane association of Na+, K+ ATPase complex (PubMed:18621045, PubMed:24792215). Regulates synaptic transmission in the amygdala, hippocampus, and cerebellum through regulation of synaptic vesicles density and their proximity to active zones leading to modulation of short-term plasticity and age-dependent anxious behavior, learning and memory (PubMed:29135436, PubMed:29780879). Regulates autophagic vacuoles (AVs) maturation by modulating the trafficking between endocytic and autophagolysosomal/lysosomal compartments, which involves vesicle fusion leading to regulation of degradation process (PubMed:16714284, PubMed:25878248, PubMed:26450516). Participates also in cellular homeostasis of compounds such as, water, ions, amino acids, proteins and lipids in several tissue namely in brain and kidney through regulation of their transport and synthesis (PubMed:19284480, PubMed:20219947, PubMed:25878248).|||Membrane|||Membrane raft|||autophagosome|||synaptosome|||trans-Golgi network http://togogenome.org/gene/10090:Cct7 ^@ http://purl.uniprot.org/uniprot/P80313|||http://purl.uniprot.org/uniprot/Q3TIJ7|||http://purl.uniprot.org/uniprot/Q3UDB1|||http://purl.uniprot.org/uniprot/Q3UIJ0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG (By similarity). Interacts with DLEC1 (By similarity).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||Heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter.|||Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. Known to play a role, in vitro, in the folding of actin and tubulin.|||The N-terminus is blocked. http://togogenome.org/gene/10090:Tex22 ^@ http://purl.uniprot.org/uniprot/Q9D9U4 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||First detected in 18-day-old mice (at protein level).|||Mainly expressed in spermatocytes and spermatids in testis.|||acrosome http://togogenome.org/gene/10090:Prph ^@ http://purl.uniprot.org/uniprot/A0A2R8W6R6|||http://purl.uniprot.org/uniprot/G3X981|||http://purl.uniprot.org/uniprot/G5E846 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the intermediate filament family.|||axon http://togogenome.org/gene/10090:Gng2 ^@ http://purl.uniprot.org/uniprot/P63213 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adrenal gland and brain.|||Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma (By similarity). In this context, interacts with GNB2 (By similarity). The heterodimer formed by GNB1 and GNG2 interacts with ARHGEF5 (By similarity). The heterodimer formed by GNB1 and GNG2 interacts with GRK2 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Gm10591 ^@ http://purl.uniprot.org/uniprot/P86792|||http://purl.uniprot.org/uniprot/P86793 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Binds to CCR7 and to CXCR3. Interacts with PDPN; relocalizes PDPN to the basolateral membrane.|||Expressed strongly in lung, spleen, thymus, peripheral and mesentric lymph nodes. Also expressed in the testis, kidney, liver, and heart.|||Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Potent mesangial cell chemoattractant. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs.|||Secreted|||Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c produce identical proteins while the protein produced by Ccl21a differs at only one position. Ccl21b and Ccl21c have Leu-65 (6Ckine-Leu) while Ccl21a has 'Ser-65' (6Ckine-Ser). http://togogenome.org/gene/10090:Slfn9 ^@ http://purl.uniprot.org/uniprot/B1ARD6 ^@ Cofactor|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Schlafen family. Subgroup III subfamily.|||Can also use Mn(2+).|||Cytoplasm|||Endoribonuclease that cleaves tRNAs and rRNAs.|||In T-cells, expressed at relatively constant levels during development: expressed in immature CD3(-)CD4(-)CD8(-) T-cells (DN stage), in CD4(+)CD8(+) double-positive stage (DP) and mature CD4(+) or CD8(+) thymocytes. Expression is slightly reduced at the DP stage.|||Induced following infection. Induced in response to LPS and interferon.|||Shows a pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. http://togogenome.org/gene/10090:Dyrk3 ^@ http://purl.uniprot.org/uniprot/Q922Y0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.|||Cytoplasm|||Cytoplasmic granule|||Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (By similarity). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:12356771). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (By similarity). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (By similarity). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (By similarity). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (By similarity). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (By similarity). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (By similarity). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (By similarity). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603).|||Interacts with SIRT1.|||Mice exhibit unperturbed steady-state erythropoiesis but significantly increased reticulocyte production during stress erythropoiesis and appear to be partially protected against anemia.|||Nucleus|||Nucleus speckle|||Protein kinase activity is activated following autophosphorylation at Tyr-368.|||The N-terminal domain, which is intrinsically disordered, is required for stress granule localization.|||Ubiquitinated at anaphase by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome.|||centrosome http://togogenome.org/gene/10090:Pex5l ^@ http://purl.uniprot.org/uniprot/D3YYH0|||http://purl.uniprot.org/uniprot/F8SLP5|||http://purl.uniprot.org/uniprot/F8SLP6|||http://purl.uniprot.org/uniprot/F8SLP7|||http://purl.uniprot.org/uniprot/F8SLP8|||http://purl.uniprot.org/uniprot/F8SLP9|||http://purl.uniprot.org/uniprot/F8SLQ1|||http://purl.uniprot.org/uniprot/F8SLQ3|||http://purl.uniprot.org/uniprot/F8SLQ4|||http://purl.uniprot.org/uniprot/F8SLQ5|||http://purl.uniprot.org/uniprot/F8SLQ6|||http://purl.uniprot.org/uniprot/Q8C437 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.|||Belongs to the peroxisomal targeting signal receptor family.|||Cytoplasm|||Interacts with RAB8B (By similarity). Forms an obligate 4:4 complex with HCN2 (PubMed:22550182). Interacts with HCN3 (Ref.5).|||Membrane http://togogenome.org/gene/10090:Cldn14 ^@ http://purl.uniprot.org/uniprot/A2RSP0|||http://purl.uniprot.org/uniprot/Q9Z0S3 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At postnatal day 4, expression is apically located in the inner and outer hair cell region of the entire organ of Corti. By postnatal day 8, expression is highest in the supporting cells of the organ of Corti.|||Belongs to the claudin family.|||Cell membrane|||Expressed in all sensory epithelia of the inner ear vestibular organs, as well as in liver and kidney.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Sult2a2 ^@ http://purl.uniprot.org/uniprot/Q3UEP5 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Srp54c ^@ http://purl.uniprot.org/uniprot/E9PXC0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTP-binding SRP family. SRP54 subfamily.|||Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9. Interacts with RNPS1. Interacts with the SRP receptor subunit SRPRA.|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). As part of the SRP complex, associates with the SRP receptor (SR) component SRPRA to target secretory proteins to the endoplasmic reticulum membrane. Binds to the signal sequence of presecretory proteins when they emerge from the ribosomes. Displays basal GTPase activity, and stimulates reciprocal GTPase activation of the SR subunit SRPRA. Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SR subunit SRPRA. SR compaction and GTPase mediated rearrangement of SR drive SRP-mediated cotranslational protein translocation into the ER. Requires the presence of SRP9/SRP14 and/or SRP19 to stably interact with RNA. Plays a role in proliferation and differentiation of granulocytic cells, neutrophils migration capacity and exocrine pancreas development.|||Cytoplasm|||Endoplasmic reticulum|||Nucleus speckle|||The M domain binds the 7SL RNA in presence of SRP19 and binds the signal sequence of presecretory proteins.|||The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER. http://togogenome.org/gene/10090:Ryk ^@ http://purl.uniprot.org/uniprot/Q01887 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Cytoplasm|||Highest expression at 16 dpc when callosal axons are beginning to cross the midline. At 17 dpc-18 dpc, when the majority of axons are projecting away from the midline, expression is observed but at a lower level. Present on the cell bodies of neurons in cortical layers at 18 dpc.|||Interacts with DVL1 (via PDZ domain).|||Is detected in all the tissues. Highest levels are seen in the ovary, lung and placenta.|||May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In response to WNT3 stimulation, receptor C-terminal cleavage occurs in its transmembrane region and allows the C-terminal intracellular product to translocate from the cytoplasm to the nucleus where it plays a crucial role in neuronal development.|||Membrane|||Nucleus|||Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation.|||The extracellular WIF domain is responsible for Wnt binding. http://togogenome.org/gene/10090:Diaph3 ^@ http://purl.uniprot.org/uniprot/Q9Z207 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (PubMed:10678165, PubMed:23558171). Required for cytokinesis, stress fiber formation and transcriptional activation of the serum response factor (PubMed:10678165, PubMed:23558171). Binds to GTP-bound form of Rho and to profilin: acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization (PubMed:10678165). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (PubMed:10678165). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (PubMed:23558171).|||Belongs to the formin homology family. Diaphanous subfamily.|||Cytoplasm|||Increased expression in S phase and mitotic cells; levels decrease as cells enter in G0/G1 phase due to proteasomal degradation (at protein level).|||Nucleus|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain (PubMed:23558171). This autoinhibition is released upon competitive binding of an activated GTPase (PubMed:23558171). The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (PubMed:23558171).|||Ubiquitinated. http://togogenome.org/gene/10090:Greb1 ^@ http://purl.uniprot.org/uniprot/E0CXG4|||http://purl.uniprot.org/uniprot/Q3UHK3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GREB1 family.|||May play a role in estrogen-stimulated cell proliferation.|||Membrane|||Partially unspliced pre-RNA. http://togogenome.org/gene/10090:Adcy5 ^@ http://purl.uniprot.org/uniprot/P84309 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by forskolin. Activated by GNAS. Activity is further increased by interaction with the G protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (By similarity). Phosphorylation by RAF1 results in its activation (By similarity).|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion.|||Cell membrane|||Interacts with GNAS, GNB1 and GNG2 (By similarity). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (PubMed:21670265). Interacts with RAF1 (By similarity).|||Phosphorylated by RAF1.|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.|||cilium http://togogenome.org/gene/10090:Abhd15 ^@ http://purl.uniprot.org/uniprot/B6DQM2|||http://purl.uniprot.org/uniprot/Q5F2F2 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.|||Decreased by elevated free fatty acid levels and aging.|||Homozygous knockout mice lacking Abhd15 are fertile and newborn pups exhibit no obvious defects.|||Interacts with PDE3B; this interaction regulates PDE3B's stability and expression and, thereby, impacts the antilipolytic action of insulin.|||Mainly expressed in adipocytes and adipose depots, followed by a weak expression in liver and pancreas (PubMed:29768196). In white adipose tissue (WAT), only expressed in mature adipocytes and primary adipocytes differentiated from stromal vascular cells (SVCs), but not in undifferentiated SVCs (PubMed:29768196).|||May regulate adipocyte lipolysis and liver lipid accumulation.|||Secreted http://togogenome.org/gene/10090:Armcx1 ^@ http://purl.uniprot.org/uniprot/Q9CX83 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ After axonal injury.|||Belongs to the eutherian X-chromosome-specific Armcx family.|||Interacts with MIRO1.|||Mitochondrion|||Mitochondrion outer membrane|||Regulates mitochondrial transport during axon regeneration. Increases the proportion of motile mitochondria by recruiting stationary mitochondria into the motile pool. Enhances mitochondria movement and neurite growth in both adult axons and embryonic neurons. Promotes neuronal survival and axon regeneration after nerve injury. May link mitochondria to the Trak1-kinesin motor complex via its interaction with Miro1.|||Widely expressed in the adult nervous tissue, especially in the forebrain, including the cerebral cortex, hippocampus and thalamus. http://togogenome.org/gene/10090:Trib3 ^@ http://purl.uniprot.org/uniprot/Q8K4K2 ^@ Caution|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.|||Highly expressed in liver. Not detected in heart, brain, spleen, lung, skeletal muscle, kidney or testis.|||In liver under fasting conditions and by thapsigargin (PubMed:12749859, PubMed:12791994). Expression is activated by ATF4 in response to stress (PubMed:17369260).|||Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress (PubMed:17369260). Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress (By similarity). May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells (By similarity). Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity (PubMed:12749859, PubMed:17369260). Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation (PubMed:12791994). May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1 (PubMed:12791994). Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity (By similarity). Interacts with MAPK kinases and regulates activation of MAP kinases (By similarity). Can inhibit APOBEC3A editing of nuclear DNA (PubMed:22977230).|||Interacts with AKT1, AKT2, MAP2K1 and MAP2K7 (PubMed:12791994). Interacts with ATF4 (PubMed:12749859, PubMed:17369260). Interacts with DDIT3/CHOP and inhibits its interaction with EP300/P300 (By similarity). Interacts with APOBEC3C (By similarity). Interacts (via N-terminus) with APOBEC3A (PubMed:22977230). Interacts with RELA (By similarity).|||Nucleus|||The protein kinase domain is predicted to be catalytically inactive.|||The role of this protein in Akt activation has been demonstrated in PubMed:12749859 but Iynedjian has not been able to reproduce the result in rat hepatocytes. http://togogenome.org/gene/10090:Pou4f3 ^@ http://purl.uniprot.org/uniprot/Q63955 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator (PubMed:8290353, PubMed:7935408). Acts by binding to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes (PubMed:7935408). Involved in the auditory system development, required for terminal differentiation of hair cells in the inner ear (PubMed:8637595).|||Belongs to the POU transcription factor family. Class-4 subfamily.|||Brain.|||Cytoplasm|||Expressed in developing spinal cord from 13 dpc to postanal day 1, not expressed in adults (PubMed:8290353). Expressed by few neurons of dorsal root ganglion from, at least, 10.5 dpc to 15.5 dpc (PubMed:22326227).|||Interacts with ISL1 (PubMed:24643061).|||Mutants are deaf and show deficits in balance and coordination that become severe at about P14 and exhibit hyperactivity by 5-6 weeks.|||Nucleus http://togogenome.org/gene/10090:Gadd45a ^@ http://purl.uniprot.org/uniprot/P48316|||http://purl.uniprot.org/uniprot/Q3UMH6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GADD45 family.|||By various types of DNA damage and growth arrest.|||Interacts with AURKA, GADD45GIP1 and PCNA (By similarity). Interacts with MAPK14.|||Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase. In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity.|||Nucleus http://togogenome.org/gene/10090:St18 ^@ http://purl.uniprot.org/uniprot/Q148A0|||http://purl.uniprot.org/uniprot/Q80TY4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MYT1 family.|||Nucleus|||Repressor that binds to DNA sequences containing a bipartite element consisting of a direct repeat of the sequence 5'-AAAGTTT-3' separated by 2-9 nucleotides. Represses basal transcription activity from target promoters (By similarity). http://togogenome.org/gene/10090:Ntf5 ^@ http://purl.uniprot.org/uniprot/Q80VU4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NGF-beta family.|||Could serve as a target-derived trophic factor for sensory and sympathetic neurons.|||Secreted http://togogenome.org/gene/10090:Pth1r ^@ http://purl.uniprot.org/uniprot/P41593 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Detected in kidney.|||Interacts (via N-terminal extracellular domain) with PTHLH and PTH (PubMed:8197183). Homodimer in the absence of bound ligand. Peptide hormone binding leads to dissociation of the homodimer.|||N-glycosylated.|||Receptor for parathyroid hormone and for parathyroid hormone-related peptide (PubMed:8197183). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Rph3a ^@ http://purl.uniprot.org/uniprot/P47708 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds calcium via the C2 domains. The calcium-bound C2 domains mediate interactions with phospholipid bilayers.|||Interacts with RAB3B, RAB3C, RAB3D, RAB8A, RAB27A and RAB27B (PubMed:12578829). Interacts with RAB3A; this interaction recruits RPH3A to synaptic vesicules (By similarity). Interacts (via C2B domain) with SNAP25 (By similarity). Interacts with deubiquitinating enzyme CAND1; this interaction results in the deubiquitination of RPH3A (By similarity). Interacts with GRIN2A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity). Interacts with SNCA (By similarity).|||Membrane|||No visible phenotype. Mice are viable and fertile and do not display any physiological impairment. Additionally, synaptic properties seem unaffected.|||Plays an essential role in docking and fusion steps of regulated exocytosis (By similarity). At the presynaptic level, RPH3A is recruited by RAB3A to the synaptic vesicle membrane in a GTP-dependent manner where it modulates synaptic vesicle trafficking and calcium-triggered neurotransmitter release (By similarity). In the post-synaptic compartment, forms a ternary complex with GRIN2A and DLG4 and regulates NMDA receptor stability. Also plays a role in the exocytosis of arginine vasopressin hormone (By similarity).|||Postsynaptic cell membrane|||Specifically expressed in brain.|||Ubiquitinated. Deubiquitinated by CAND1 to prevent its degradation.|||dendritic spine|||synaptic vesicle membrane http://togogenome.org/gene/10090:Krt23 ^@ http://purl.uniprot.org/uniprot/Q544I8|||http://purl.uniprot.org/uniprot/Q99PS0 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Pde6h ^@ http://purl.uniprot.org/uniprot/P61249 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the rod/cone cGMP-PDE gamma subunit family.|||Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.|||Tetramer composed of two catalytic chains (alpha and beta), and two inhibitory chains (gamma).|||The C-terminal region is important in conferring inhibition. http://togogenome.org/gene/10090:Fabp5 ^@ http://purl.uniprot.org/uniprot/Q05816|||http://purl.uniprot.org/uniprot/Q497I3 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Deficient mice display resistance to diet-induced obesity, decreased adipose tissue and imporved glucose tolerance and insulin sensitivity.|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Intracellular carrier for long-chain fatty acids and related active lipids, such as endocannabinoids, that regulate the metabolism and actions of the ligands they bind (PubMed:8608126, PubMed:12540600). In addition to the cytosolic transport, selectively delivers specific fatty acids from the cytosol to the nucleus, wherein they activate nuclear receptors (By similarity). Delivers retinoic acid to the nuclear receptor peroxisome proliferator-activated receptor delta; which promotes proliferation and survival (PubMed:17512406). May also serve as a synaptic carrier of endocannabinoid at central synapses and thus controls retrograde endocannabinoid signaling (PubMed:29531087). Modulates inflammation by regulating PTGES induction via NF-kappa-B activation, and prostaglandin E2 (PGE2) biosynthesis during inflammation (PubMed:29440395). May be involved in keratinocyte differentiation (By similarity).|||Monomer.|||Nucleus|||Postsynaptic density|||Secreted|||Synapse|||While human FABP5 can exist as a monomer as well as a domain-swapped dimer, mouse is found only in the monomeric form.|||Widely expressed. http://togogenome.org/gene/10090:Thop1 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZY0|||http://purl.uniprot.org/uniprot/Q8C1A5 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M3 family.|||Binds 1 zinc ion per subunit.|||Binds 1 zinc ion.|||Cytoplasm|||Involved in the metabolism of neuropeptides under 20 amino acid residues long (PubMed:10969067). Involved in cytoplasmic peptide degradation. Able to degrade the amyloid-beta precursor protein and generate amyloidogenic fragments (By similarity). Also acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By similarity).|||Monomer. http://togogenome.org/gene/10090:Zc3h12b ^@ http://purl.uniprot.org/uniprot/G3X9I7|||http://purl.uniprot.org/uniprot/Q3UYJ7 ^@ Similarity ^@ Belongs to the ZC3H12 family. http://togogenome.org/gene/10090:Or5ac24 ^@ http://purl.uniprot.org/uniprot/Q8VGP9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tcf12 ^@ http://purl.uniprot.org/uniprot/Q61286 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed during development of the central nervous system, in particular in proliferating neuroblasts and in cells at the initial stages of differentiation. Also expressed at high levels in morphogenetically active regions such as limb buds, somites and mesonephric tubules. Expression decreases once cellular differentiation is over.|||Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers with myogenin, E12 and ITF2 proteins and RUNX1T1 (By similarity). Interacts with PTF1A. Interacts with NEUROD2. Interacts with BHLHA9.|||Mice are smaller than their wild-type littermates and fail to thrive 14 days after birth.|||Nucleus|||Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (PubMed:18214987). May be involved in the functional network that regulates the development of the GnRH axis (By similarity).|||Widely expressed. http://togogenome.org/gene/10090:Trp63 ^@ http://purl.uniprot.org/uniprot/O88898|||http://purl.uniprot.org/uniprot/Q3UVI3|||http://purl.uniprot.org/uniprot/Q569E5|||http://purl.uniprot.org/uniprot/Q5CZX0 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes.|||Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Activates transcription of the p21 promoter (By similarity). Activates RIPK4 transcription. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge.|||Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression.|||Belongs to the p53 family.|||Binds 1 zinc ion per subunit.|||Binds DNA as a homotetramer.|||Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity.|||Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity. Interacts with HIPK2. Interacts with SSRP1, leading to stimulate coactivator activity. Interacts with PDS5A. Interacts (via activation domain) with NOC2L (By similarity). Interacts with WWP1.|||Cytoplasm|||Expressed in the basal layer and a small number of cells in the spinous layer of the tongue at P20.|||Expressed in the epidermis from 7.5 dpc, prior to onset of epithelial stratification.|||Expressed in the epidermis from 9.5 dpc, after the onset of epithelial stratification but prior to terminal differentiation.|||Induced by DNA damaging agents.|||Intron retention.|||May be sumoylated.|||Nucleus|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||Produced by alternative splicing of isoform 2.|||The transactivation inhibitory domain (TID) can interact with, and inhibit the activity of the N-terminal transcriptional activation domain of TA*-type isoforms.|||Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein.|||Widely expressed, notably in thymus, prostate, placenta and skeletal muscle, although the precise isoform varies according to tissue type. Progenitor cell layers of skin, breast and prostate express high levels of DeltaN-type isoforms. http://togogenome.org/gene/10090:Gm1673 ^@ http://purl.uniprot.org/uniprot/Q3UR78 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Deficient males are sterile, whereas females are fertile. Deficient mice display defective sperm migration from the uterus into the oviduct and poor sperm binding to the egg zona pellucida. Mice are infertile because of deficient epididymal differentiation and deficient sperm maturation.|||Expression is enriched in both male and female reproductive organs, including the testis, epididymis, seminal vesicles, coagulating glands, ovary, and uterus, and in various non-reproductive organs,such as brain, thymus,liver and brain. In testis expressed in both germ cells and Sertoli cells, (PubMed:37095084). Specifically expressed during neocortex and cerebellum development.|||First expressed in the cerebral cortex after the preplate stage (>E12). At embryonic stage 15.5 dpc and up to 17.5 dpc, it is expressed in cortical plate and in the marginal zone, whereas in adult brain, it is present in all cortical and subcortical regions of the brain. In the developing cerebellum, expressed in the intermediate zone at stage 17.5 dpc, in the molecular layer in newborn, and in the granular as well as molecular layer in adult. In the adult brain, expression in interneurons is also observed (PubMed:21287218). Expression in the testis increases postnatally (PubMed:37095084).|||Interacts with NELL2; triggers epididymal differentiation.|||Secreted|||Testis-derived lumicrine factor that triggers epididymal differentiation and sperm maturation. http://togogenome.org/gene/10090:Syncrip ^@ http://purl.uniprot.org/uniprot/A0A0R4J259|||http://purl.uniprot.org/uniprot/G3UZ48|||http://purl.uniprot.org/uniprot/Q3TRV3|||http://purl.uniprot.org/uniprot/Q7TMK9 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in spinal cord at 14 dpc and onwards.|||Heterogeneous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1 and isoform 2 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences (By similarity). Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself (By similarity). May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain (By similarity). Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 2 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins.|||Identified in the spliceosome C complex. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a mRNP granule complex, at least composed of ACTB, ACTN4, DHX9, ERG, HNRNPA1, HNRNPA2B1, HNRNPAB, HNRNPD, HNRNPL, HNRNPR, HNRNPU, HSPA1, HSPA8, IGF2BP1, ILF2, ILF3, NCBP1, NCL, PABPC1, PABPC4, PABPN1, RPLP0, RPS3, RPS3A, RPS4X, RPS8, RPS9, SYNCRIP, YBX1 and untranslated mRNAs. Interacts with GTPBP1 (By similarity). Isoform 1 is a component of the APOB mRNA editosome complex. Isoform 1 interacts with APOBEC1 and A1CF. Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR, HNRPD and SYNCRIP. Isoform 2 interacts with HNRPR. Interacts with POLR2A hyperphosphorylated C-terminal domain. Interacts with HABP4 (By similarity). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Isoform 1 and isoform 2 interact with SMN. Isoform 2 interacts through its C-terminal domain with SYT7, SYT8 and SYT9. The non-phosphorylated and phosphorylated forms are colocalized with PAIP1 in polysomes.|||May be due to a competing donor splice site and to an exon inclusion.|||Microsome|||Nucleus|||Phosphorylated on tyrosine. The membrane-bound form found in microsomes is phosphorylated in vitro by insulin receptor tyrosine kinase (INSR). Phosphorylation is inhibited upon binding to RNA, whereas the cytoplasmic form is poorly phosphorylated.|||The domain containing eight Arg-Gly-Gly repeats (RGG/RXR-box) may be involved in RNA-binding and protein-protein interactions. It is methylated by PRMT1, and essential for nuclear localization (By similarity).|||Ubiquitous. Detected in heart, brain, spleen, lung, liver, skeletal muscle, adipocytes, kidney and testis.|||nucleoplasm http://togogenome.org/gene/10090:Susd4 ^@ http://purl.uniprot.org/uniprot/Q8BH32 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.|||High expression in brain and eye, with weaker expression in spinal cord and testis. Detected in white matter of brain and in the outer segments of photoreceptors.|||In contrast some authors report that SUSD4 acts as an activator of the alternative complement pathway, while having no effect on the classical pathway (in vitro) (PubMed:20348246). These contradictory results with human may lie in the differences in protein expression, in this study SUSD4 is expressed in bacteria and not in eukaryotic cells.|||Membrane http://togogenome.org/gene/10090:Bpifb6 ^@ http://purl.uniprot.org/uniprot/Q8BU51 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||Secreted http://togogenome.org/gene/10090:Cx3cl1 ^@ http://purl.uniprot.org/uniprot/O35188 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble short 80 kDa form may be released by proteolytic cleavage from the long membrane-anchored form.|||Belongs to the intercrine delta family.|||By 12-O-tetradecanoylphorbol-13-acetate (TPA) and lipopolysaccharides (LPS) in bone marrow stroma cells.|||Cell membrane|||Chemokine that acts as a ligand for both CX3CR1 and integrins ITGAV:ITGB3 and ITGA4:ITGB1 (PubMed:10187784, PubMed:18971423). The CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chemotaxis (PubMed:10382755, PubMed:9177350, PubMed:10187784, PubMed:18971423). Regulates leukocyte adhesion and migration processes at the endothelium (PubMed:10382755, PubMed:9177350). Can activate integrins in both a CX3CR1-dependent and CX3CR1-independent manner (By similarity). In the presence of CX3CR1, activates integrins by binding to the classical ligand-binding site (site 1) in integrins (By similarity). In the absence of CX3CR1, binds to a second site (site 2) in integrins which is distinct from site 1 and enhances the binding of other integrin ligands to site 1 (By similarity).|||Highest levels in brain (PubMed:9177350, PubMed:9479488, PubMed:9845323, PubMed:10508268). Lower levels in kidney, heart and lung (PubMed:9177350, PubMed:9479488, PubMed:10508268). Also found in skeletal muscle and testis (PubMed:9177350, PubMed:9479488). Highly expressed in lesional smooth muscle cells, but not macrophages (PubMed:12569158). Low levels of ABCD-3 mRNA were also found in anti-CD40-stimulated splenic B-cells, but not in resting B-cells. Also expressed in dendritic cells (PubMed:10508268).|||Monomer (By similarity). Forms a ternary complex with CX3CR1 and ITGAV:ITGB3 or ITGA4:ITGB1 (By similarity).|||No visible phenotype (PubMed:11287620). Mice develop normally and have normal migration of leukocytes to lymphoid tissue and peripheral sites in several models of inflammation (PubMed:11287620).|||Secreted|||The membrane-bound form promotes adhesion of those leukocytes to endothelial cells.|||The soluble form is chemotactic for T-cells and monocytes, but not for neutrophils. http://togogenome.org/gene/10090:Mtbp ^@ http://purl.uniprot.org/uniprot/Q8BJS8 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the MTBP family.|||Death between E3.5 and E7.5. Mice containing a heterozygous deletion of this gene coupled with heterozygous deletion of TP53 exhibit an increased incidence of metastatic tumors.|||Expressed in small intestine and spleen at low levels, in the ovary at intermediate levels and in the testis and thymus at high levels.|||Interacts with MDM2.|||May play a role in MDM2-dependent p53/TP53 homeostasis in unstressed cells. Inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability. This promotes MDM2-mediated ubiquitination of p53/TP53 and its subsequent degradation. Inhibits cell migration in vitro and suppresses the invasive behavior of tumor cells. http://togogenome.org/gene/10090:Lig1 ^@ http://purl.uniprot.org/uniprot/P37913|||http://purl.uniprot.org/uniprot/Q3TSU8|||http://purl.uniprot.org/uniprot/Q3U4X8|||http://purl.uniprot.org/uniprot/Q8R055 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP-dependent DNA ligase family.|||DNA ligase that seals nicks in double-stranded during DNA repair. Also involved in DNA replication and DNA recombination.|||Interacts with PCNA. Interacts with POLB.|||Nucleus http://togogenome.org/gene/10090:Csgalnact1 ^@ http://purl.uniprot.org/uniprot/Q8BJQ9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Deficient mice are viable and fertile, but decreased body weight and length and abnormal cartilage (PubMed:21148564).|||Golgi stack membrane|||High expression in developing cartilage and during chondrocyte differentiation.|||Transfers 1,4-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of glucuronic acid (GlcUA). Required for addition of the first GalNAc to the core tetrasaccharide linker and for elongation of chondroitin chains. Important role in chondroitin chain biosynthesis in cartilage formation, and subsequent endochondral ossification (PubMed:17145758, PubMed:21148564). Moreover, is involved in the metabolism of aggrecan (PubMed:21148564). http://togogenome.org/gene/10090:Tgtp2 ^@ http://purl.uniprot.org/uniprot/Q3T9E4|||http://purl.uniprot.org/uniprot/Q62293 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in thymus and lymph nodes, predominantly T-cells. Not expressed by immature CD4(+) CD8(+) thymocytes (at protein level) (PubMed:7836757). Expressed in IFNG-stimulated macrophages (PubMed:7884320). Expressed at low levels in unstimulated astrocytes (PubMed:19285957). Due to sequence similarity with Tgtp1, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene.|||Expressed in thymus and lymph nodes, predominantly T-cells. Not expressed by immature CD4(+) CD8(+) thymocytes (at protein level) (PubMed:7836757). Expressed in IFNG-stimulated macrophages (PubMed:7884320). Expressed at low levels in unstimulated astrocytes (PubMed:19285957). Due to sequence similarity with Tgtp2, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene.|||Golgi apparatus|||In macrophages, up-regulated by IFNG, but not by IL2, IL4, IL10, nor TNF (PubMed:7884320). Up-regulated by IFNG in lymph node cells and thymocytes and other cell types (PubMed:7836757, PubMed:9725230, PubMed:24563254). In astrocytes, up-regulated by TNF and IFNG; when both cytokines are combined, the effect is synergistic (PubMed:19285957). Due to sequence similarity with Tgtp1, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene (Probable).|||In macrophages, up-regulated by IFNG, but not by IL2, IL4, IL10, nor TNF (PubMed:7884320). Up-regulated by IFNG in lymph node cells and thymocytes and other cell types (PubMed:7836757, PubMed:9725230, PubMed:24563254). In astrocytes, up-regulated by TNF and IFNG; when both cytokines are combined, the effect is synergistic (PubMed:19285957). Due to sequence similarity with Tgtp2, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene (Probable).|||Involved in innate cell-autonomous resistance to intracellular pathogens, such as Toxoplasma gondii (PubMed:19265156, PubMed:20109161, PubMed:24563254). During avirulent type II T. gondii infection, recruited to the parasitophorous vacuole (PV) membrane, leading to PV vesiculation and rupture, and subsequent digestion of the parasite within the cytosol (PubMed:19265156, PubMed:24563254). Not recruited to virulent type I T. gondii PV membrane (PubMed:19265156). May confer an antiviral state for vesicular stomatitis virus (PubMed:9725230).|||The gene Tgtp1 belongs to a large family of eutherian IFNG-inducible GTPases, called immunity-related p47 GTPases, which comprises a variable amount of paralogs depending upon the species studied. In C57BL/6J mice, there is over 20 genes, whereas humans have only one ortholog. Tgtp1 closest paralog is Tgtp2. Both genes encode identical proteins. At the nucleotide sequence level, their CDSs differ at only 4 positions. Consequently it is almost impossible to assign unambiguously to one gene or the other experimental data published in the literature.|||The gene Tgtp1 belongs to a large family of eutherian IFNG-inducible GTPases, called immunity-related p47 GTPases, which comprises a variable amount of paralogs depending upon the species studied. In C57BL/6J mice, there is over 20 genes, whereas humans have only one ortholog. Tgtp2 closest paralog is Tgtp1. Both genes encode identical proteins. At the nucleotide sequence level, their CDSs differ at only 4 positions. Consequently it is almost impossible to assign unambiguously to one gene or the other experimental data published in the literature. http://togogenome.org/gene/10090:Chn2 ^@ http://purl.uniprot.org/uniprot/Q3V2R3|||http://purl.uniprot.org/uniprot/Q80XD1 ^@ Activity Regulation|||Function|||Subcellular Location Annotation ^@ GTPase-activating protein for p21-rac.|||In the inactive state, the N terminus protrudes into the active site of the Rho-GAP domain, sterically blocking Rac binding. Phospholipid binding to the Phorbol-ester/DAG-type zinc-finger/C1 domain triggers the cooperative dissociation of these interactions, allowing the N-terminus to move out of the active site and thereby activating the enzyme (By similarity).|||Membrane http://togogenome.org/gene/10090:Gfap ^@ http://purl.uniprot.org/uniprot/P03995 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Brain; isoform 2 expressed at 20-fold lower level than isoform 1.|||Cytoplasm|||GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.|||Interacts with PSEN1 (via N-terminus).|||Interacts with SYNM.|||Phosphorylated by PKN1. http://togogenome.org/gene/10090:Mad2l1 ^@ http://purl.uniprot.org/uniprot/Q9Z1B5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAD2 family.|||Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (By similarity). In the closed conformation (C-MAD2) forms a heterotetrameric complex with MAD1L1 at unattached kinetochores during prometaphase, and recruits an open conformation of MAD2L1 (O-MAD2) which then promotes the conversion of O-MAD2 to C-MAD2 (By similarity). Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate (By similarity).|||Cytoplasm|||Monomer and homodimer (By similarity). Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (By similarity). In the closed and open conformation, interacts with MAD1L1 (By similarity). Formation of a heterotetrameric core complex containing two molecules each of MAD1L1 and of MAD2L1 promotes binding of another molecule of MAD2L1 to each MAD2L1, resulting in a heterohexamer (By similarity). Interacts with MAD2L1BP (By similarity). Interacts with ADAM17/TACE (By similarity). Interacts with CDC20 (By similarity). Dimeric MAD2L1 in the closed conformation interacts with CDC20 (By similarity). Monomeric MAD2L1 in the open conformation does not interact with CDC20 (By similarity). CDC20 competes with MAD1L1 for MAD2L1 binding (By similarity). In the closed conformation, interacts with BUB1B (By similarity). Interacts with TTK (By similarity). Interacts with TPR (By similarity). Binds to UBD (via ubiquitin-like 1 domain) during mitosis (By similarity). Interacts with isoform 1 and isoform 2 of NEK2 (By similarity). Interacts with HSF1; this interaction occurs in mitosis (By similarity).|||Nucleus|||Phosphorylated on multiple serine residues. The level of phosphorylation varies during the cell cycle and is highest during mitosis. Phosphorylation abolishes interaction with MAD1L1 and reduces interaction with CDC20. Phosphorylated by NEK2 (By similarity).|||The protein has two highly different native conformations, an inactive open conformation that cannot bind CDC20 and that predominates in cytosolic monomers, and an active closed conformation. The protein in the closed conformation preferentially dimerizes with another molecule in the open conformation, but can also form a dimer with a molecule in the closed conformation. Formation of a heterotetrameric core complex containing two molecules of MAD1L1 and of MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation and the conversion of the open to the closed form, and thereby promotes interaction with CDC20 (By similarity).|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Irf8 ^@ http://purl.uniprot.org/uniprot/P23611|||http://purl.uniprot.org/uniprot/Q3UCV9|||http://purl.uniprot.org/uniprot/Q544J7 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IRF family.|||By interferon gamma.|||Cytoplasm|||Expressed in bone marrow macrophages (at protein level) (PubMed:32741026). Mainly expressed in lymphoid tissues (PubMed:2111015). Predominantly expressed in CD8(+)-expressing dendritic cells (PubMed:12393690).|||Interacts with COPS2 (By similarity). Interacts (via C-terminus) with TRIM21 (via C-terminus). Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct. Interacts with SPI1 (By similarity).|||Mice display an absence of interferon (IFN)-producing cells and show impaired IFN production in response to viral infection (PubMed:12461077). Complete absence of plasmacytoid dendritic cells (pDCs) and conventional CD8(+)-expressing dendritic cells (cDCs) (PubMed:12393690, PubMed:12538667, PubMed:23382217). Mice display reduced autoimmunity (PubMed:23382217).|||Nucleus|||Sumoylated with SUMO3. Desumoylated by SENP1.|||Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:2111015, PubMed:12393690). Can both act as a transcriptional activator or repressor (PubMed:2111015). Plays a negative regulatory role in cells of the immune system (PubMed:2111015). Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (PubMed:12393690, PubMed:22992524). Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (PubMed:12461077, PubMed:12393690, PubMed:12538667, PubMed:23382217). Positively regulates macroautophagy in dendritic cells (By similarity). Acts as a transcriptional repressor of osteoclast differentiation factors such as NFATC1 and EEIG1 (PubMed:32741026).|||Ubiquitinated (PubMed:17579016). Ubiquitination by TRIM21 in macrophages, a process that is strongly increased upon interferon gamma stimulation, leds to the enhanced transcriptional activity of target cytokine genes (PubMed:17579016). Ubiquitination leads to its degradation by the proteasome (By similarity). http://togogenome.org/gene/10090:Dmrtc2 ^@ http://purl.uniprot.org/uniprot/Q8CGW9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DMRT family.|||Expressed in gonads from 11.5 dpc.|||Expressed in testis. Highly expressed in ovary.|||May be involved in sexual development.|||Nucleus http://togogenome.org/gene/10090:Psap ^@ http://purl.uniprot.org/uniprot/B2RUD7|||http://purl.uniprot.org/uniprot/E9PZ00|||http://purl.uniprot.org/uniprot/Q3TWM9|||http://purl.uniprot.org/uniprot/Q3TXJ0|||http://purl.uniprot.org/uniprot/Q3UAS4|||http://purl.uniprot.org/uniprot/Q3UE29|||http://purl.uniprot.org/uniprot/Q3UFE8|||http://purl.uniprot.org/uniprot/Q61207|||http://purl.uniprot.org/uniprot/Q8BFQ1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.|||Lysosome|||Prosaposin: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.|||Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.|||Saposin-B is a homodimer. Prosaposin exists as a roughly half-half mixture of monomers and disulfide-linked dimers. Monomeric prosaposin interacts (via C-terminus) with sortilin/SORT1, the interaction is required for targeting to lysosomes. Interacts with GRN; facilitates lysosomal delivery of progranulin from the extracellular space and the biosynthetic pathway (PubMed:26370502).|||Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.|||Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).|||Saposins are specific low-molecular mass non-enzymatic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.|||Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.|||Secreted http://togogenome.org/gene/10090:Morc2a ^@ http://purl.uniprot.org/uniprot/Q69ZX6 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATPase activity is dependent of phosphorylation by PAK1 and presence of DNA.|||Chromosome|||Essential for epigenetic silencing by the HUSH complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing (By similarity). Represses germ cell-related genes and L1 retrotransposons in collaboration with SETDB1 and the HUSH complex, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark (PubMed:29728365). Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression. During DNA damage response, regulates chromatin remodeling through ATP hydrolysis (By similarity). During DNA damage response, may regulate chromatin remodeling through ATP hydrolysis (By similarity).|||Expressed in the axons and Schwann cells of peripheral nerves. Expressed in testes (PubMed:29329290).|||Homodimerizes upon ATP-binding and dissociate upon ATP hydrolysis; homodimerization is required for gene silencing (By similarity). Binds histone H3 independently of the methylation status at 'Lys-9' (PubMed:29728365). Interacts with HDAC4. Interacts with FAM208A/TASOR and MPHOSPH8; the interactions associate MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci (By similarity). Interacts with Morc2b (PubMed:29329290).|||Nucleus|||Nucleus matrix|||Phosphorylated by PAK1 at Ser-737 upon DNA damage. Phosphorylation is required for ATPase activity and recruitment to damaged chromatin.|||cytosol http://togogenome.org/gene/10090:Slc35c1 ^@ http://purl.uniprot.org/uniprot/Q78H73|||http://purl.uniprot.org/uniprot/Q8BLX4|||http://purl.uniprot.org/uniprot/Q8BZX8|||http://purl.uniprot.org/uniprot/Q8C0J3|||http://purl.uniprot.org/uniprot/Q8R2I1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Antiporter specific for GDP-l-fucose and depending on the concomitant reverse transport of GMP. Involved in GDP-fucose import from the cytoplasm into the Golgi lumen.|||Belongs to the TPT transporter family. SLC35C subfamily.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Srrm3 ^@ http://purl.uniprot.org/uniprot/Q80WV7 ^@ Function|||Similarity ^@ Belongs to the CWC21 family.|||May play a role in regulating breast cancer cell invasiveness. May be involved in RYBP-mediated breast cancer progression. http://togogenome.org/gene/10090:Pfpl ^@ http://purl.uniprot.org/uniprot/Q5RKV8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MPEG1 family.|||Cytoplasmic vesicle membrane|||Membrane http://togogenome.org/gene/10090:Or52p2 ^@ http://purl.uniprot.org/uniprot/Q8VG23 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnf1 ^@ http://purl.uniprot.org/uniprot/E9PYC0|||http://purl.uniprot.org/uniprot/Q7TSH7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. F (TC 1.A.1.2) subfamily. Kv5.1/KCNF1 sub-subfamily.|||Heteromultimer with KCNG3, KCNG4 and KCNV2. Interacts with DLG1 (By similarity).|||Membrane|||Putative voltage-gated potassium channel.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Pgap1 ^@ http://purl.uniprot.org/uniprot/Q3UUQ7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GPI inositol-deacylase family.|||Endoplasmic reticulum membrane|||Involved in inositol deacylation of GPI-anchored proteins. GPI inositol deacylation may important for efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi (By similarity). http://togogenome.org/gene/10090:Or52e19b ^@ http://purl.uniprot.org/uniprot/L7N1Y4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ear10 ^@ http://purl.uniprot.org/uniprot/Q923L6 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Trim11 ^@ http://purl.uniprot.org/uniprot/Q99PQ2 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated upon DNA stimulation; autoubiquitination promotes interaction with SQSTM1/p62 and recruitment of AIM2 to autophagosomes.|||Belongs to the TRIM/RBCC family.|||Binds cytoplasmic tail of integrin alpha-1 (By similarity). Interacts with the HN peptide (PubMed:12670303). Interacts with PHOX2B (PubMed:18275850). Interacts (when autoubiquitinated) with SQSTM1/p62; promoting AIM2 recruitment to autophagosomes (By similarity). Interacts with AIM2; promoting its autophagy-dependent degradation (By similarity).|||By PAX6.|||Cytoplasm|||E3 ubiquitin-protein ligase that promotes the degradation of insoluble ubiquitinated proteins, including insoluble PAX6, poly-Gln repeat expanded HTT and poly-Ala repeat expanded ARX (PubMed:18628401). Mediates PAX6 ubiquitination leading to proteasomal degradation, thereby modulating cortical neurogenesis (PubMed:18628401). May also inhibit PAX6 transcriptional activity, possibly in part by preventing the binding of PAX6 to its consensus sequences (PubMed:18628401). May contribute to the regulation of the intracellular level of HN (humanin) or HN-containing proteins through the proteasomal degradation pathway (PubMed:12670303). Mediates MED15 ubiquitination leading to proteasomal degradation (By similarity). May contribute to the innate restriction of retroviruses (PubMed:18248090). Upon overexpression, reduces HIV-1 and murine leukemia virus infectivity, by suppressing viral gene expression (PubMed:18248090). Antiviral activity depends on a functional E3 ubiquitin-protein ligase domain (PubMed:18248090). May regulate TRIM5 turnover via the proteasome pathway, thus counteracting the TRIM5-mediated cross-species restriction of retroviral infection at early stages of the retroviral life cycle (PubMed:18248090). Acts as an inhibitor of the AIM2 inflammasome by promoting autophagy-dependent degradation of AIM2 (By similarity). Mechanistically, undergoes autoubiquitination upon DNA stimulation, promoting interaction with AIM2 and SQSTM1/p62, leading to AIM2 recruitment to autophagosomes (By similarity).|||Expressed in embryonic central nervous system (CNS), kidney, thymus and gut.|||Nucleus|||The B30.2 domain may be involved cellular protein quality control by promoting the degradation of insoluble ubiquitinated proteins.|||The coiled-coil domain and the B30.2 domain are both necessary for interaction with HN and PAX6. They are also involved in MED15-binding. http://togogenome.org/gene/10090:B4galnt3 ^@ http://purl.uniprot.org/uniprot/A0A1D5RMF7|||http://purl.uniprot.org/uniprot/Q6L8S8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Golgi stack membrane|||Membrane|||Transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine-beta-benzyl with a beta-1,4-linkage to form N,N'-diacetyllactosediamine, GalNAc-beta-1,4-GlcNAc structures in N-linked glycans and probably O-linked glycans.|||Transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine-beta-benzyl with a beta-1,4-linkage to form N,N'-diacetyllactosediamine, GalNAc-beta-1,4-GlcNAc structures in N-linked glycans and probably O-linked glycans. Mediates the N,N'-diacetyllactosediamine formation on gastric mucosa (By similarity). http://togogenome.org/gene/10090:Or1f19 ^@ http://purl.uniprot.org/uniprot/Q8VGB9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc12a9 ^@ http://purl.uniprot.org/uniprot/Q99MR3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SLC12A transporter family.|||Cell membrane|||Interacts with SLC12A1.|||May be an inhibitor of SLC12A1. Seems to correspond to a subunit of a multimeric transport system and thus, additional subunits may be required for its function (By similarity). http://togogenome.org/gene/10090:Serpinb7 ^@ http://purl.uniprot.org/uniprot/Q6P3F8|||http://purl.uniprot.org/uniprot/Q9D695 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Might function as an inhibitor of Lys-specific proteases. Might influence the maturation of megakaryocytes via its action as a serpin (By similarity). http://togogenome.org/gene/10090:Nr1h4 ^@ http://purl.uniprot.org/uniprot/Q3V1T8|||http://purl.uniprot.org/uniprot/Q60641 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by EP300 (PubMed:18842595). Lys-228 as is the major acetylation site for EP300; the dynamicly regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1 (By similarity). Elevated acetylation levels are found in metabolic disease states (mouse models of obesity and type II diabetes) (PubMed:19883617).|||Activates transcription of IBAP and SDC1.|||Activation protects mice against cholestasis, development of chronical intestinal inflammation and fibrosis. May suppress intestinal tumorigenesis.|||Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. Reduced bile acid pools and reduced fecal bile acid excretion.|||Expressed in liver and kidney. Expressed in pancreatic beta cells and macrophages. Expressed in the villus epithelium in adult ileum, with highest expression in the intervillus regions. Expression in colon is reduced by inflammation.|||Heterodimer with RXRA; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators (By similarity). Binds DNA predominantly as a heterodimer with RXRA (PubMed:7760852). After activation by agonist binding interacts with coactivators. Interacts with PPARGC1A, SMARCA4 and EP300 (PubMed:14729567, PubMed:18842595, PubMed:19805516). Interacts with NCOA1, NCOA2, CARM1, SETD7, PRMT1, GPS2, SMARCA4 and MED1. Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP. Interacts with PAGR1 and NCOA6; indicative for an association with an MLL2/MLL3 complex (ASCOM) (By similarity). Interacts with NR5A2 (PubMed:20483916).|||Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved in innate immune response (PubMed:11030617, PubMed:21383957, PubMed:22820415). The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5'-AGGTCA-3' in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity (PubMed:20091679, PubMed:20483916). In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis) (PubMed:21383957, PubMed:25651182, PubMed:25545350). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine) (PubMed:21383957). In ileal enterocytes activates FABP6/IBABP (involved in cytosolic transport), SLC51A/OSTA and SLC51B/OSTB (involved in secretion of conjugated BAs to the portal blood), and repressor NR0B2/SHP thereby indirectly inhibiting SLC10A2/ASBT (involved in BA uptake) (By similarity). In the intestine activates FGF15 expression and secretion leading to hepatic CYP7A1 repression; the function also involves the coordinated induction of hepatic KLB/beta-klotho expression (PubMed:16213224, PubMed:26505219). Transcriptional activation of FABP6/IBAP and SCD1 but not of ABCB11 is isoform-specific (PubMed:12393883). Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA (By similarity). Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 isoform SREBP-1C (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly) (PubMed:12421815, PubMed:15146238). Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance) (PubMed:11579204). Transrepresses APOA1 probably involving a monomeric competition with NR2A1 for binding to a DR1 element (PubMed:21804189). Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase) (PubMed:12891557, PubMed:15146238). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance (PubMed:15564327, PubMed:16446356, PubMed:16557297, PubMed:16410358, PubMed:20447400). Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier (PubMed:16473946, PubMed:21242261). Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells (PubMed:19864602). Mediates transrepression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2 (By similarity). Involved in the TLR9-mediated protective mechanism in intestinal inflammation (PubMed:23372731). Plays a anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling (PubMed:18972444).|||Methylation may increase transactivation of target genes.|||Mouse Nr1h4/FXR is less responsive to CDCA and more responsive to cholic acid (CA) than human FXR.|||Nucleus|||Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||Produced by alternative splicing of isoform 3.|||Sumoylated upon ligand binding. http://togogenome.org/gene/10090:Trim69 ^@ http://purl.uniprot.org/uniprot/Q80X56 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays an important role in antiviral immunity by restricting different viral infections including dengue virus or vesicular stomatitis indiana virus. Ubiquitinates viral proteins such as dengue virus NS3 thereby limiting infection. In addition, acts as a key mediator of type I interferon induced microtubule stabilization by directly associating to microtubules independently of its E3 ligase activity. Plays also a role in cataract formation together with TP53. Mechanistically, inhibits UVB-induced cell apoptosis and reactive oxygen species (ROS) production by inducing TP53 ubiquitination.|||Expressed in spermatid.|||Homo-multimer; required for antiviral activity (By similarity). Interacts with PML (PubMed:12837286).|||Male TRIM69-knockout mice have normal fertility. Appearance of testes, testis/body weight ratios, testicular histomorphology, and the number and quality of sperm are consistent with wild-type mice.|||Nucleus|||Nucleus speckle|||Phosphorylated. Phosphorylation is necessary for nuclear localization.|||The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity and for nuclear localization and aggregation. http://togogenome.org/gene/10090:Oacyl ^@ http://purl.uniprot.org/uniprot/Q8BML2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the acyltransferase 3 family.|||Membrane http://togogenome.org/gene/10090:Cidec ^@ http://purl.uniprot.org/uniprot/P56198 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CIDE family.|||Endoplasmic reticulum|||Expressed almost exclusively in adipose tissue, including subcutaneous and epididymal white adipose tissue (at protein level) (PubMed:1339452, PubMed:12910269, PubMed:18654663, PubMed:18682832, PubMed:22245780). Although abundantly present in brown adipose tissue at the mRNA level, the protein is almost undetectable in this tissue, or at moderate levels (PubMed:12910269, PubMed:18654663, PubMed:22245780). Expressed in the mammary gland, in stromal adipose tissue, but becomes undetectable at the end of pregnancy and during lactation (at protein level) (PubMed:22245780). Expressed at low levels in skeletal muscle and heart (PubMed:23233732).|||Homodimer (PubMed:24025675, PubMed:23481402). Homooligomer; undergoes liquid-liquid phase separation (LLPS) via its N-terminus, facilitating lipid droplet fusion, occurs at the lipid droplet contact sites (PubMed:34508658). Interacts with CIDEA (By similarity). Interacts with PLIN1 (PubMed:23481402). Interacts with NFAT5; this interaction is direct and retains NFAT5 in the cytoplasm (By similarity). Interacts with CEBPB (PubMed:22245780). Interacts with isoform CLSTN3beta of CLSTN3; inhibiting the lipid transferase activity of CIDEC (PubMed:36477540).|||Lipid droplet|||Lipid transferase specifically expressed in white adipose tissue, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion (PubMed:18334488, PubMed:22144693, PubMed:26733203, PubMed:30361435, PubMed:36477540). Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage (PubMed:18334488, PubMed:18682832, PubMed:22144693, PubMed:26733203). Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by undergoing liquid-liquid phase separation (LLPS) and promoting directional net neutral lipid transfer from the smaller to larger lipid droplets (PubMed:18334488, PubMed:22144693). The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair (PubMed:18334488, PubMed:22144693). Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1 (PubMed:23481402). May also act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH (PubMed:22245780). When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment (By similarity).|||Mutant animals are born in a Mendelian ratio and appear physically normal at birth (PubMed:18654663). Mice display increased energy expenditure, lower levels of plasma triglycerides and free fatty acids (PubMed:18654663, PubMed:18682832). The body weights of wild-type and mutant mice fed a standard diet do not differ up to 14 weeks of age, nor does food intake (PubMed:18654663). From 16 weeks of age, the body weight of mutant mice significantly decreases compared with that of wild-type mice (PubMed:18654663, PubMed:18682832). When animals are fed a high-fat diet, the gain in body weight is significantly smaller for mutant mice than for wild-type (PubMed:18654663). Under these feeding conditions, mutant mice are also protected from insulin resistance and from accumulation of fat in the liver (PubMed:18654663). The body temperature do not differ significantly between mutant and wild-type mice maintained at room temperature, but the basal rate of oxygen consumption is significantly increased in mutants (PubMed:18654663).|||Nucleus|||The CIDE-N domain is involved in homodimerization which is crucial for its function in promoting lipid exchange and transfer.|||The RKKR polybasic motif mediates binding to acidic phospholipids, such as phosphatidic acid, phosphatidylinositol and phosphatidylserine, inhibiting the ability to mediate lipid droplet fusion.|||Ubiquitinated and targeted to proteasomal degradation, resulting in a short half-life (about 15 minutes in 3T3-L1 cells) (PubMed:20089860). Protein stability depends on triaclyglycerol synthesis, fatty acid availability and lipid droplet formation (PubMed:20089860).|||Up-regulated during differentiation into adipocytes in various cell lines, including TA1 and 3T3-L1 (PubMed:1339452, PubMed:18334488, PubMed:18654663, PubMed:22245780). Decreases in the mammary gland during pregnancy from day 14.5 until 18.5, when it becomes hardly detectable, and during lactation (PubMed:1339452, PubMed:18334488, PubMed:18654663, PubMed:22245780).|||Up-regulated under conditions that enhance triacylglycerol deposition, including rosiglitazone treatment and high-fat diet (PubMed:18509062, PubMed:20089860). This up-regulation is mediated by PPARG (PubMed:20089860). Up-regulated by isoproterenol, a beta-agonist, and oleic acid treatment (PubMed:20089860). This induction is due to protein stabilization (PubMed:20089860). Down-regulated upon hypertonic conditions (PubMed:23233732). http://togogenome.org/gene/10090:Ppp3ca ^@ http://purl.uniprot.org/uniprot/P63328 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+) (PubMed:26794871). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+) (PubMed:26794871). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A (PubMed:26794871). The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A (PubMed:26794871). Inhibited by immunosuppressant drug FK506 (tacrolimus) in complex with FKBP12 and also by immunosuppressant drug cyclosporin A (CsA) in complex with PPIA/cyclophilin A; the inhibition is Ca(2+)-dependent (By similarity).|||Belongs to the PPP phosphatase family. PP-2B subfamily.|||Binds 1 Fe(3+) ion per subunit.|||Binds 1 zinc ion per subunit.|||Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:7791792, PubMed:26794871). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (By similarity). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (By similarity). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (By similarity). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (By similarity). Dephosphorylates and inactivates transcription factor ELK1 (By similarity). Dephosphorylates DARPP32 (By similarity). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (By similarity). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (PubMed:15509543). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (PubMed:16735444). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (PubMed:21435446). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (PubMed:10200317). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (PubMed:19626032). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (PubMed:16286645). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (PubMed:16968888). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (PubMed:12773574). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (PubMed:26029823). Required for antigen-specific T-cell proliferation response (PubMed:8627154). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (By similarity). Negatively regulates SLC9A1 activity (By similarity).|||Cell membrane|||Cytoplasm|||Expressed in the kidney (at protein level) (PubMed:15509543). Expressed in the salivary gland (at protein level) (PubMed:21435446). Expressed in osteoblasts and bone marrow (at protein level) (PubMed:16286645). Expressed in the brain and the bicep, tricep, soleus and gastrocnemius muscles (at protein level) (PubMed:12773574). Abundantly expressed in the dentate gyrus and the CA1 and CA3 regions of the hippocampus (at protein level) (PubMed:10200317). Expressed in T-lymphocytes (at protein level) (PubMed:8627154). Expressed in embryonic stem cells (PubMed:8627154).|||Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B) (PubMed:26794871). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CA/calcineurin A, calcineurin B and calmodulin (By similarity). Interacts (via calcineurin B binding domain) with regulatory subunit PPP3R1/calcineurin B (PubMed:26794871). Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+) (By similarity). Forms a complex composed of MYOZ2 and ACTN1 (PubMed:11114196). Within the complex interacts with MYOZ2 (PubMed:11114196). Interacts with MYOZ1 (PubMed:11114196). Interacts with MYOZ3 (By similarity). Interacts with CIB1; the interaction increases upon cardiomyocyte hypertrophy (PubMed:20639889). Interacts with CHP1 and CHP2 (By similarity). Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (PubMed:30611118). Interacts with DNM1L; the interaction dephosphorylates DNM1L and promotes its translocation to mitochondria (By similarity). Interacts with CMYA5; this interaction represses calcineurin activity in muscle (PubMed:21427212). Interacts (constitutively active form) with SYNPO2 (By similarity). Interacts with scaffold protein AKAP5 (via IAIIIT motif); the interaction recruits PPP3CA to the plasma membrane following L-type Ca(2+)-channel activation (By similarity). Interacts with NFATC2 (By similarity). Interacts with RCAN3 (By similarity). Interacts with PPIA (By similarity). Interacts with RCAN1 (PubMed:12809556). Interacts with UNC119 (PubMed:31696965). Interacts with C16orf74 (via PxIxIT motif, when phosphorylated on 'Thr-79') (By similarity). Interacts (via N-terminus) with MAP3K14/NIK (via C-terminus and kinase domain) (PubMed:26029823). Interacts with TRAF3 (PubMed:26029823). Interacts with SPATA33 (via PQIIIT motif) (By similarity).|||Knockout mice are significantly smaller at postnatal day 18 (P18), including significantly reduced weights of the liver and kidneys (PubMed:15509543, PubMed:16735444). Decreased blood glucose levels (PubMed:16735444). Decreased lumber spine, tibia, and total body bone mass density evident at 6 weeks of age, evidence of decreased density in the lumber spine as early as 3 weeks of age (PubMed:16286645). No change in overall muscle weight (PubMed:12773574). Decreased femur length, reduced cortical trabecular bone thickness (PubMed:16286645). Significantly reduced number of differentiated osteoclasts (PubMed:16968888). Reduced mitochondrial oxidative capacity in slow and intermediate muscle fiber types (PubMed:12773574). Reduced slow and intermediate program type muscle fibers in the biceps and triceps (PubMed:12773574). Decreased number of slow program type muscle fibers and NFAT activity in the soleus (PubMed:12773574). Kidney size and development is normal at P4, however by P18 kidneys show an obvious delay in maturation, displaying a decreased overall mass, poorly defined medullary rays and decreased cortical mass (PubMed:15509543). Upon examination the outer strip of the medulla and cortical regions of the kidneys are significantly decreased (PubMed:15509543). In the cortex there is a persistence of poorly developed surface glomeruli due to attenuation of mesangial cells numbers and a lack of maturation of tubules in the nephrogenic zone (PubMed:15509543). Reduced proliferation and increased apoptosis of cells within the nephrogenic zone at P18, potentially as a result of increased p27 expression (PubMed:15509543). Impaired kidney function evident by increased kidney collagen deposition, serum creatinine levels and decreased urine creatinine concentration from P4 onwards (PubMed:15509543, PubMed:16735444). Loss of AQP2 phosphorylation in response to vasopressin and decreased localization to the apical membrane of inner medullary collecting duct cells (PubMed:16735444). Most mice die between P21 and P28 as a result of progressive kidney failure (PubMed:15509543). Increased salivary osmolality despite normal electrolyte composition and protein content (PubMed:21435446). Decreased activity of amylase, peroxidase, lysozyme and sialic acid in the saliva (PubMed:21435446). Decreased number of secretory vesicles, mucosal acini cell size and protein content of serosal acini in the submandibular glands (PubMed:21435446). Decreased activity of calcineurin in the salivary glands (PubMed:21435446). Decreased thickness of the epidermal stratum spinosum, a thickened corneum and increased sloughing-off of keratinocytes in newborn mice (PubMed:19626032). Decreased thickness of the stratum spinosum is still evident at 4 weeks of age along with decreased skin elasticity (PubMed:19626032). Increased apoptosis in the supra-basal layers and the stratum spinosum of the epidermis (PubMed:19626032). Decrease in NFATc activity in basal epidermal cells and impaired differentiation of epidermal keratinocytes as shown by aberrant expression of the differentiation markers KRT14, KRT10 and IVL (PubMed:19626032). Decreased calcineurin activity in the brain and significant reduction in homosynaptic depotentiation (PubMed:10200317). Decreased calcineurin activity in T-lymphocytes and loss of T-lymphocyte proliferation in response to antigen stimulation (PubMed:8627154).|||Possible isomerization of Pro-309 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.|||The autoinhibitory domain prevents access to the catalytic site.|||The autoinhibitory segment prevents access to the substrate binding site.|||Z line|||dendritic spine|||sarcolemma http://togogenome.org/gene/10090:Klk1b24 ^@ http://purl.uniprot.org/uniprot/Q61754 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Entrep2 ^@ http://purl.uniprot.org/uniprot/Q6A044 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ENTREP family.|||Membrane http://togogenome.org/gene/10090:Vmn2r25 ^@ http://purl.uniprot.org/uniprot/W4VSP2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4a74 ^@ http://purl.uniprot.org/uniprot/A2AT78 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Col24a1 ^@ http://purl.uniprot.org/uniprot/Q30D77 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fibrillar collagen family.|||Expressed in skeleton. Found at ossification centers of the craniofacial, axial and appendicular skeleton. Also expressed in retina and to a lower extent in cornea, skin and tendon.|||Expression is confined to the developing eye and skeleton. First level of expression are detectable around 15 dpc.|||Involved in osteoblast differentiation.|||extracellular matrix http://togogenome.org/gene/10090:Inpp5d ^@ http://purl.uniprot.org/uniprot/Q9ES52 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane.|||Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.|||By activin/TGF-beta (at protein level). Regulated by the Smad pathway. Isoform 3 is expressed during myeloid development.|||Cell membrane|||Cytoplasm|||Expressed in late primitive-streak stage embryos (7.5 dpc), when hematopoiesis is thought to begin, and the expression is restricted to the hematopoietic lineage in embryo. In adults expression continues to be in the majority of cells from hematopoietic origin, including granulocytes, monocytes and lymphocytes, and is also found in the spermatids of the testis.|||Interacts with tyrosine phosphorylated form of SHC1 (PubMed:8654924, PubMed:8643691, PubMed:10068665, PubMed:9083021, PubMed:9099679, PubMed:10395202). Interacts with tyrosine phosphorylated form of DOK1 (PubMed:11031258). Interacts with tyrosine phosphorylated form of DOK3 (PubMed:14993273). Interacts with tyrosine phosphorylated form of SLAMF1/CD150 (By similarity). Interacts with PTPN11/SHP-2 in response to IL-3 (PubMed:9110989, PubMed:9393882). Interacts with receptor EPOR (PubMed:10660611). Interacts with receptors MS4A2/FCER1B and FCER1G (By similarity). Interacts with receptors FCGR2B and FCGR3 (PubMed:10395202, PubMed:11016922, PubMed:10779347, PubMed:15456754, PubMed:12393695). Interacts with receptor FCGR2A, leading to regulate gene expression during the phagocytic process (PubMed:12370370). Interacts with GRB2 (PubMed:8643691, PubMed:10068665). Interacts with PLCG1 (PubMed:16000869). Interacts with tyrosine kinases SRC and TEC (PubMed:10794720, PubMed:15492005). Interacts with CRKL (PubMed:11031258). Interacts with c-Met/MET (PubMed:11896575). Interacts with MILR1 (tyrosine-phosphorylated) (PubMed:20526344). Isoform 5 interacts with IL6ST/gp130 (PubMed:17105399). Can weakly interact (via NPXY motif 2) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (PubMed:11247302). Interacts (via SH2 domain) with tyrosine phosphorylated KLRC1 (via ITIM).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane raft|||Mice are viable and fertile. They however fail to thrive and only 40% survive by 14 weeks of age. Mortality is associated with extensive consolidation of the lungs resulting from infiltration by myeloid cells. Increased numbers of granulocyte-macrophage progenitors are observed in both the bone marrow and spleen. Absence of Inpp5d leads to steel factor-induced degranulation of mast cells. They also display increased numbers of osteoclast precursors leading to a severe osteoporosis.|||Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (By similarity). Also able to hydrolyze the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (PubMed:9367159). Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity. Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression.|||Specifically expressed in immune and hematopoietic cells. Levels vary considerably within this compartment. Lost during erythropoiesis when erythroid cells become Ter119+. Increases substantially with T-cell maturation and when resting B-cells are activated. Also present in mature granulocytes, monocyte/macrophages, mast cells and platelets. Isoform 5 is the only form expressed in embryonic stem (ES) cells and is coexpressed with other isoforms in hematopoietic stem cells, and disappears with differentiation.|||The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.|||The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or PTPN11/SHP-2. It competes with that of GRB2 for binding to phosphorylated SHC1 to inhibit the Ras pathway. It is also required for tyrosine phosphorylation.|||Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as cytokines, growth factors, antibodies, chemokines, integrin ligands and hypertonic and oxidative stress. Phosphorylated upon IgG receptor FCGR2B-binding.|||cytoskeleton http://togogenome.org/gene/10090:Trappc14 ^@ http://purl.uniprot.org/uniprot/Q3UTZ3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the multisubunit TRAPP II complex, which includes at least TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC4, TRAPPC5, TRAPPC6A/B, TRAPPC9, TRAPPC10 and TRAPPC14. TRAPPC9, TRAPPC10 and TRAPPC14 are specific subunits of the TRAPP II complex. Interacts with alpha-tubulin during mitosis. Interacts with RAB3IP (via the N-terminal region); this interaction mediates RAB3IP association with the TRAPP II complex. Interacts with TRAPPC10. Interacts with FBF1.|||Midbody|||Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether. TRAPPC14 is dispensable for TRAPPII complex integrity but mediates RAB3IP preciliary vesicle trafficking to the mother centriole during ciliogenesis. Modulates YAP1 activity as transcriptional regulator.|||Vesicle|||spindle http://togogenome.org/gene/10090:Il17ra ^@ http://purl.uniprot.org/uniprot/Q60943 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 virus protein ORF8.|||(Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway.|||Cell membrane|||Forms heterodimers with IL17RC; the heterodimer binds IL17A and IL17F homodimers as well as the heterodimer formed by IL17A and IL17F (PubMed:20554964). Forms complexes with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (By similarity). IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer forms predominantly complexes with IL17RC homodimer (By similarity). IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer (By similarity). IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (By similarity). IL17RA chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (By similarity). Interacts with TRAF3IP2 (By similarity). Forms heterodimers with IL17RE; the heterodimer binds IL17C (PubMed:21993848).|||Mutant mice are susceptibile to S.aureus cutaneous infection (PubMed:20364087). Mutant mice are susceptible to A. fumigatus pulmonary infection characterized by excessive mucus production, goblet cell hyperplasia and exacerbated T-helper 2 allergic inflammation (PubMed:28813677).|||Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911633, PubMed:20554964, PubMed:8777726, PubMed:27923703). Receptor for IL17F (PubMed:17911633, PubMed:20554964). Binds to IL17A with higher affinity than to IL17F (PubMed:17911633). Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (By similarity). Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (By similarity). Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (By similarity). Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (PubMed:21993848, PubMed:20364087). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (PubMed:18157131). Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (PubMed:19144317). Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity (PubMed:27795421). Contributes to influenza A virus (H1N1) clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (PubMed:26735852). Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848, PubMed:21993849, PubMed:21982598).|||Up-regulated in brain upon West Nile virus infection.|||Widely expressed (PubMed:21993848). Highly expressed in T cells and macrophages (PubMed:19144317). Highly expressed in B-1a B cells and at a lower extent in B-1b and B-2 B cells (at protein level) (PubMed:26735852). http://togogenome.org/gene/10090:Iqce ^@ http://purl.uniprot.org/uniprot/Q6PCQ0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE (PubMed:24582806). Interacts (via N-terminus) with EFCAB7 (via EF-hands 1 and 2); this interaction anchors the EVC-EVC2 complex in a signaling microdomain at the base of cilia and stimulates the Hedgehog (Hh) pathway. Interacts with EVC2 (via N-terminal end) (PubMed:24582806). Interacts with EVC (PubMed:24582806).|||Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling (PubMed:24582806). Required for proper limb morphogenesis (By similarity).|||cilium membrane http://togogenome.org/gene/10090:Foxa3 ^@ http://purl.uniprot.org/uniprot/P35584 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expression peaks around day 15.5 of gestation. Expressed from day 6 to day 70 during postnatal testicular development.|||Interacts with FOXA2.|||Nucleus|||Reduced expression levels of several HNF3 target genes (phosphoenolpyruvate carboxykinase, transferrin, tyrosine aminotransferase) by 50 to 70%,. The germinal epithelium of testes is characterized by a loss of germ cells secondary to an increase in germ cell apoptosis that ultimately leads to a Sertoli cell-only syndrome. Significantly lower blood glucose in fasted mice.|||Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine), also present additionally in ovary, testis, heart, and adipose tissue, but missing from lung.|||Transcription factor that is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites (By similarity). Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; activates GLUT2 transcription. Involved in regulation of neuronal-specific transcription. Involved in regulation of spermatogenesis; required for the maintenance of the testicular germ cell population and male fertility. http://togogenome.org/gene/10090:Bloc1s2 ^@ http://purl.uniprot.org/uniprot/Q9CWG9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BLOC1S2 family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes (By similarity). In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals (PubMed:16760431, PubMed:21998198). The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension (PubMed:19546860). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (By similarity).|||Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts directly with BLOC1S1, BLOC1S3, BLOC1S4, BLOC1S5 and SNAPIN (PubMed:15102850). The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos (PubMed:21998198). Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN (By similarity). Interacts with gamma-tubulin (By similarity). Interacts with IFT57 (PubMed:18188704).|||Lysosome membrane|||centrosome http://togogenome.org/gene/10090:Sycn ^@ http://purl.uniprot.org/uniprot/Q8VCK7 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Contains intrachain disulfide bonds.|||Functions in exocytosis in pancreatic acinar cells regulating the fusion of zymogen granules with each other. May have a pore-forming activity on membranes and regulate exocytosis in other exocrine tissues.|||Mice display reduced rates of protein synthesis and intracellular transport of secretory proteins. According to PubMed:15040787 mice lacking Sycn display atrophy of the pancreas associated with an elevated amylase content.|||Monomer and homooligomer; most probably hexameric. Interacts with GP2 (By similarity).|||Zymogen granule lumen|||Zymogen granule membrane http://togogenome.org/gene/10090:Or4x6 ^@ http://purl.uniprot.org/uniprot/Q8VEZ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trpc5os ^@ http://purl.uniprot.org/uniprot/Q3UHV4 ^@ Caution ^@ Encoded in an intron of the TRPC5 gene (opposite strand). May be a non-coding RNA. http://togogenome.org/gene/10090:Rnh1 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSG5|||http://purl.uniprot.org/uniprot/Q91VI7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Forms high-affinity heterodimers with RNASE1, ANG and RNASE2.|||Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis (By similarity).|||Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis.|||The LRR domain forms a horseshoe-shaped structure that interacts tightly with target RNases via a large protein interaction surface on its interior side. http://togogenome.org/gene/10090:Mustn1 ^@ http://purl.uniprot.org/uniprot/Q99JI1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MUSTANG family.|||May be involved in the development and regeneration of the musculoskeletal system.|||Nucleus http://togogenome.org/gene/10090:Skap2 ^@ http://purl.uniprot.org/uniprot/Q3UND0 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SKAP family.|||By IL-6 in myeloid cells.|||Cytoplasm|||Dephosphorylated on Tyr-75 by PTPN22 (By similarity). Phosphorylated by FYN on Tyr-260. In case of infection with Y.pseudotuberculosis, dephosphorylated by bacterial phosphatase yopH.|||Expressed in kidney, lung, liver, spleen, bone marrow and testis. Present in T-cells, B-cells, and all cells of the myelomonocytic lineage. Present in all brain regions, with highest levels in neurons from the Purkinje cell layer, hippocampal gyrus, cortex and substantia nigra (at protein level).|||Interacts with LAT, GRB2, PTK2B and PRAM1 (By similarity). Homodimer. Interacts with FYB1, which is required for SKAP2 protein stability. Interacts with PTPNS1. Part of a complex consisting of SKAP2, FYB1 and PTPNS1. Part of a complex consisting of SKAP2, FYB1 and LILRB3. May interact with actin. May interact with FYN, HCK and LYN. Interacts with FASLG (By similarity).|||May be involved in B-cell and macrophage adhesion processes. In B-cells, may act by coupling the B-cell receptor (BCR) to integrin activation. May play a role in src signaling pathway.|||Mice are healthy and do not display any obvious abnormality. They have normal T-cell, platelet and macrophage function, but show reduced levels of spontaneous immunoglobulins in the serum, and defects in B-cell proliferation.|||The SH3 domain interacts with FYB1 and PTK2B. http://togogenome.org/gene/10090:Mknk1 ^@ http://purl.uniprot.org/uniprot/A2A8W8|||http://purl.uniprot.org/uniprot/O08605|||http://purl.uniprot.org/uniprot/Q3U1I8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Dual phosphorylation of Thr-209 and Thr-214 activates the kinase. Phosphorylation of Thr-344 activates the kinase. MAPK3/ERK1 is one of the kinases which activate MKNK1/MNK1. Phosphorylation by PAK2 leads to a reduced phosphorylation of EIF4G1 (By similarity).|||Interacts with the C-terminal regions of EIF4G1 and EIF4G2. Also binds to dephosphorylated ERK1 and ERK2, and to the p38 kinases.|||May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap.|||Phosphorylated and activated by the p38 kinases and kinases in the Erk pathway.|||Ubiquitously expressed in all tissues examined, with high levels in skeletal muscle. http://togogenome.org/gene/10090:Was ^@ http://purl.uniprot.org/uniprot/P70315|||http://purl.uniprot.org/uniprot/Q53WY0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds the Arp2/3 complex (By similarity). Interacts with CDC42, RAC, NCK, HCK, FYN, SRC kinase FGR, BTK, ABL1, PSTPIP1, WIP, and to the p85 subunit of PLC-gamma (PubMed:9488710). Interacts (via C-terminus) with ALDOA (By similarity). Interacts with NCK1 (via SH3 domains) (PubMed:8910519). Interacts with FCHSD2 (PubMed:23437151).|||Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria. In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Nucleus|||Phosphorylated at Tyr-293 by FYN and HCK, inducing WAS effector activity after TCR engagement. Phosphorylation at Tyr-293 enhances WAS activity in promoting actin polymerization and filopodia formation.|||The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-terminal WH2 domain in the autoinhibited state of the protein. Binding of Rho-type GTPases to the CRIB induces a conformation change and leads to activation.|||The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand.|||cytoskeleton http://togogenome.org/gene/10090:Rnf152 ^@ http://purl.uniprot.org/uniprot/Q8BG47 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNF152 family.|||E3 ubiquitin-protein ligase that acts as a negative regulator of mTORC1 signaling by mediating ubiquitination of RagA/RRAGA and RHEB (PubMed:25936802). Catalyzes 'Lys-63'-linked polyubiquitination of RagA/RRAGA in response to amino acid starvation, thereby regulating mTORC1 signaling (PubMed:25936802). Also mediates monoubiquitination of RHEB, promoting its association with the TSC-TBC complex and subsequent inhibition (By similarity). Also mediates 'Lys-48'-linked polyubiquitination of target proteins and their subsequent targeting to the proteasome for degradation (By similarity). Induces apoptosis when overexpressed (By similarity).|||Interacts with RRAGA (inactive GDP-bound form); stimulated by amino acid starvation (By similarity). Interacts with SEC16A (PubMed:29300766).|||Lysosome membrane|||Mice lacking Rnf152 do not show overt embryonic development defect.|||Ubiquitinated. Autoubiquitinated in vitro, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Ubqln3 ^@ http://purl.uniprot.org/uniprot/Q8C5U9 ^@ Tissue Specificity ^@ Testis-specific (at protein level). http://togogenome.org/gene/10090:Gm5938 ^@ http://purl.uniprot.org/uniprot/A2AEN9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Kcnk4 ^@ http://purl.uniprot.org/uniprot/O88454|||http://purl.uniprot.org/uniprot/Q0VD85 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by arachidonic acid and other unsaturated fatty acids (PubMed:9628867). Not affected by volatile general anesthetics such as chloroform, diethyl ether, halothane and isoflurane (PubMed:10321245).|||Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Cell membrane|||Channel opening is brought about by a conformation change that involves buckling of the second transmembrane helix and affects the position and orientation of the fourth transmembrane helix.|||Expressed in brain, spinal cord and eye. Not detected in heart, skeletal muscle, liver, lungs, kidney and testis.|||Homodimer; disulfide-linked.|||Membrane|||Mutant mice show increased sensitivity to pain caused by pressure, but also by heat.|||N-glycosylated.|||Voltage-insensitive potassium channel (PubMed:9628867). Channel opening is triggered by mechanical forces that deform the membrane. Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the sensory perception of pain caused by pressure (PubMed:19279663). Plays a role in the perception of pain caused by heat (PubMed:19279663). http://togogenome.org/gene/10090:Mvd ^@ http://purl.uniprot.org/uniprot/Q3UYC1|||http://purl.uniprot.org/uniprot/Q99JF5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the diphosphomevalonate decarboxylase family.|||Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoids and sterol synthesis.|||Cytoplasm|||Homodimer.|||Was originally thought to be located in the peroxisome (By similarity). However, was later shown to be cytosolic (PubMed:12736493). http://togogenome.org/gene/10090:Gamt ^@ http://purl.uniprot.org/uniprot/O35969 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RMT2 methyltransferase family.|||Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. Important in nervous system development.|||Highly expressed in testis, caput epididymis, ovary, and liver. In the testis, localized primarily in Sertoli cells. Expressed in brain with high levels in oligodendrocytes and olfactory ensheathing glia. Moderate levels of expression in astrocytes.|||Monomer.|||microvillus http://togogenome.org/gene/10090:Tifa ^@ http://purl.uniprot.org/uniprot/Q793I8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter molecule that plays a key role in the activation of pro-inflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:11798190). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (By similarity). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of pro-inflammatory NF-kappa-B signaling (By similarity).|||Belongs to the TIFA family.|||Cytoplasm|||Highly expressed in the spleen and at lower levels in heart, brain, lung, liver, kidney and testes.|||Homooligomer; homooligomerizes following phosphorylation at Thr-9 (By similarity). Interacts with IRAK1, TRAF2 and TRAF6 (PubMed:11798190). Interacts with TIFAB; binding to TIFAB inhibits TRAF6 activation, possibly by inducing a conformational change in TIFA (By similarity). Interacts with ZCCHC11; binding to ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B (By similarity).|||Phosphorylated at Thr-9 following detection of ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) by ALPK1. Phosphorylation at Thr-9 by ALPK1 leads to the formation of an intermolecular binding between the FHA domain and phosphorylated Thr-9, promoting TIFA oligomerization and TIFA-mediated NF-kappa-B activation.|||The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B. http://togogenome.org/gene/10090:Taf13 ^@ http://purl.uniprot.org/uniprot/P61216 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF13 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts with TBP, and more strongly with TAF10 and TAF11.|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. TAF13, together with TAF11 and TBP, play key roles during promoter binding by the TFIID and TFIIA transcription factor complexes.|||The binding of TAF10 and TAF11 requires distinct domains of TAF13. http://togogenome.org/gene/10090:Ptger4 ^@ http://purl.uniprot.org/uniprot/P32240|||http://purl.uniprot.org/uniprot/Q91VE4 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant expression in ileum, thymus and mastocytoma P-815 cells. Also observed in lung, spleen, heart and uterus.|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with FEM1A.|||Membrane|||Phosphorylation mediates agonist-mediated desensitization by promoting cytoplasmic retention.|||Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.|||Was originally designated as the EP2 subtype. http://togogenome.org/gene/10090:Cd177 ^@ http://purl.uniprot.org/uniprot/Q8R2S8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in neutrophils.|||Found in a complex with integrin ITGAM/CD11b and ITGB2/CD18. Interacts with PECAM1 (via Ig-like C2-type domain 6); the interaction is Ca(2+)-dependent; the interaction is direct. Interacts with serine protease PRTN3/myeloblastin; the interaction tethers PRTN3 to the cell surface; the interaction is direct.|||In association with beta-2 integrin heterodimer ITGAM/CD11b and ITGB2/CD18, mediates activation of TNF-alpha primed neutrophils including degranulation and superoxide production (By similarity). In addition, by preventing beta-2 integrin internalization and attenuating chemokine signaling favors adhesion over migration (By similarity). Heterophilic interaction with PECAM1 on endothelial cells plays a role in neutrophil transendothelial migration in vitro (By similarity). However, appears to be dispensable for neutrophil recruitment caused by bacterial infection in vivo (PubMed:25359465). Acts as a receptor for the mature form of protease PRTN3 allowing its display at the cell surface of neutrophils (By similarity). By displaying PRTN3 at the neutrophil cell surface, may play a role in enhancing endothelial cell junctional integrity and thus vascular integrity during neutrophil diapedesis (By similarity).|||Mice are viable, fertile and are born at the expected Mendelian rate. Slight decrease in blood CD11b(+)Ly-6G(-)Ly-6C(+) monocyte and CD11b(+)Ly-6G(+)Ly-6C(+) neutrophil populations. Lymphocyte and myeloid development is not affected. In S.aureus-mediated skin infection, recruitment of neutrophils and monocytes to the infection site is transiently reduced. In thioglycolate-induced peritonitis, recruitment of neutrophils is normal. http://togogenome.org/gene/10090:Rap1gap ^@ http://purl.uniprot.org/uniprot/A2ALS5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in brain cortex and striatum (at protein level). Detected in brain cortex and striatum.|||GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state.|||Golgi apparatus membrane|||Homodimer and heterodimer with RAP1B. http://togogenome.org/gene/10090:Btg1c ^@ http://purl.uniprot.org/uniprot/Q3V0X0 ^@ Similarity ^@ Belongs to the BTG family. http://togogenome.org/gene/10090:Tmem80 ^@ http://purl.uniprot.org/uniprot/Q9D3H0 ^@ Subcellular Location Annotation ^@ Membrane|||cilium http://togogenome.org/gene/10090:Gnal ^@ http://purl.uniprot.org/uniprot/Q3TY78|||http://purl.uniprot.org/uniprot/Q66L47|||http://purl.uniprot.org/uniprot/Q8BHK8|||http://purl.uniprot.org/uniprot/Q8CGK7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the G-alpha family. G(s) subfamily.|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with GAS2L2 (PubMed:23994616).|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(olf) alpha mediates signal transduction within the olfactory neuroepithelium and the basal ganglia. May be involved in some aspect of visual transduction, and in mediating the effect of one or more hormones/neurotransmitters (By similarity). http://togogenome.org/gene/10090:Pnma8a ^@ http://purl.uniprot.org/uniprot/Q80VM8 ^@ Similarity ^@ Belongs to the PNMA family. http://togogenome.org/gene/10090:Ulk1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B3|||http://purl.uniprot.org/uniprot/O70405|||http://purl.uniprot.org/uniprot/Q6PB82 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by KAT5/TIP60 under autophagy induction, promoting protein kinase activity.|||Acetylation by KAT5/TIP60 stimulates the protein kinase activity (PubMed:22539723). The protein kinase activity is activated by unanchored 'Lys-63'-linked polyubiquitin chains: unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32 in an AMBRA1-dependent manner (By similarity).|||Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.|||Interacts with GABARAP and GABARAPL2 (By similarity). Interacts (via C-terminus) with ATG13 (PubMed:19258318). Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19258318). Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation (By similarity). Interacts with FEZ1; SCOC interferes with FEZ1-binding (By similarity). Interacts with TBC1D14 (By similarity). Interacts (phosphorylated form) with TRIM5 (By similarity). When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21 (By similarity). Interacts with SESN2 (PubMed:25040165). Interacts with SQSTM1 (PubMed:25040165). Interacts with C9orf72 (By similarity). Interacts with WDR45 (By similarity). Interacts with ATG13; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with WIPI2 (By similarity). Interacts with ATP2A2 (By similarity). Interacts with AMBRA1 (By similarity). Interacts with Irgm1; promoting the coassembly of ULK1 and BECN1 (By similarity).|||Preautophagosomal structure|||Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21205641, PubMed:21258367). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:19258318). Plays a role early in neuronal differentiation and is required for granule cell axon formation (By similarity). May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165). Phosphorylates FLCN, promoting autophagy (By similarity). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (By similarity). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (By similarity).|||Serine/threonine-protein kinase involved in autophagy in response to starvation.|||Ubiquitinated via 'Lys-63'-linkage by a complex composed of AMBRA1 and TRAF6 following autophagy induction, promoting ULK1 stability and kinase activity. Deubiquitinated by USP20; leading to ULK1 stability and autophagy initiation.|||cytosol http://togogenome.org/gene/10090:Qars ^@ http://purl.uniprot.org/uniprot/Q8BML9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Cytoplasm|||Glutamine--tRNA ligase. Plays a critical role in brain development.|||Monomer. Part of a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:12060739). Interacts with RARS1. Part of a complex composed of RARS1, QARS1 and AIMP1 (By similarity).|||cytosol http://togogenome.org/gene/10090:Rer1 ^@ http://purl.uniprot.org/uniprot/Q9CQU3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RER1 family.|||Golgi apparatus membrane|||Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment. http://togogenome.org/gene/10090:Lpar1 ^@ http://purl.uniprot.org/uniprot/P61793|||http://purl.uniprot.org/uniprot/Q544V2 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cell surface|||Detected in lung (PubMed:21821728). Detected in oligodendrocytes in corpus callosum in brain cortex (at protein level) (PubMed:25226845). Expressed within the embryonic cerebral cortex, where it is enriched in the ventricular zone (PubMed:8922387). In the adult brain, also expressed in oligodendrocytes, as well as Schwann cells of the peripheral nervous system (PubMed:9013780, PubMed:25226845). Expressed in many other tissues, including lung, heart, intestine, spleen, thymus, and stomach. No expression in liver (PubMed:9013780). Detected in kidney and testis (PubMed:9013780, PubMed:12215548). Detected in embryonic fibroblasts (PubMed:12215548). Detected in adult lung fibroblasts and lung endothelial cells (PubMed:18066075). Detected in dorsal root ganglion and dorsal root (PubMed:15195086). Detected in astrocytes (PubMed:17692995). Detected in bone (PubMed:21569876).|||Endosome|||Interacts with RALA and GRK2 (By similarity). Interacts with GNAQ and GNA13 (PubMed:23478264). Interacts with CD14; the interaction is enhanced by exposure to bacterial lipopolysaccharide (LPS) (PubMed:21821728).|||Membrane|||Mutant embryos are detected at the expected Mendelian rate, but there is about 50% perinatal lethality. This is mostly due to suckling defects, possibly because the neonates cannot find a nipple. Surviving mice are smaller, and they have shorter snouts and more widely spaced eyes than wild-type. A small percentage of the embryos and neonates display frontal hematomas. Besides, a small percentage of the embryos display exencephaly (PubMed:11087877). These mice display also deformity of the rib cage with sterno-distal rib fusions, shorter, crooked sternebrae, delayed vertebral calcification and closure of the thoracic spine (PubMed:21569876). Their small size is due to growth defects of limbs and vertebrae (PubMed:21569876). Mutant mice display decreased bone mass, as well as defects in proliferation and osteoblastic differentiation of bone marrow mesenchymal stem cells (PubMed:21569876). A spontaneous variant (the Malaga variant) that appeared among the descendants of the original knockout mice shows almost complete perinatal viability, but the mice still present small size, shorter snouts, wider-spaced eyes and reduced brain volume (PubMed:17656621). Compared to wild-type, the Malaga variants display smaller olfactory bulbs, and generally a smaller brain with slightly decreased thickness of the brain cortex and subtle defects in cortex development (PubMed:17656621). The hippocampus appears normal at birth, but displays a reduced number of cell divisions in adult dentate gyrus, both under normal conditions and when mice are exposed to a stimulating environment that promotes neurogenesis (PubMed:18708146). Compared to wild-type, the newly formed hippocampus cells show reduced survival (PubMed:18708146). Newly formed granule cells display defects in their maturation (PubMed:18708146). Mutant mice present subtle myelination defects in the brain cortex (PubMed:25226845). Mutant mice display minor defects in somesthesis, olfaction, grasping and keeping their equilibrium, and show decreased sensitivity to pain caused by heat (PubMed:19689455). Mutant mice do not display allodynia and hyperalgesia after nerve injury and are protected against demyelination after nerve injury (PubMed:15195086). Mutant mice display increased Schwann cell apoptosis in sciatic nerve, but this still leaves the majority of Schwann cells intact and does not cause any visible effect on movement (PubMed:11087877). Mutant mice display decreased exploration in the open field and increased anxiety-like responses to novelty; they also show subtle deficits in spatial learning and memory (PubMed:19689455). Mutant mice show blunted responses to bacterial lipopolysaccharide (LPS) and show reduced acute inflammation in response to LPS (PubMed:21821728). Mutant mice show decreased migration of fibroblasts to sites of lung injury, decreased injury-induced vascular leak, and are protected against the development of lung fibrosis after bleomycin treatment (PubMed:18066075). Mutant mice have reduced levels of proliferating epithelial cells in their intestinal crypts, and the cells do not migrate normally from the bottom of the crypts up into the villi (PubMed:23478264). Mutant mice show impaired repair after wounding of the intestinal mucosa (PubMed:23478264).Mutant mice have less body weight, but increased brown and white adipose tissue (PubMed:20358347). Contrary to wild-type, mutant mice do not increase their food consumption on a high fat diet and do not gain weight on a high fat diet (PubMed:20358347). Mice deficient in both Lpar1 and Lpar2 have the same phenotype as mice lacking Lpar1, excepting a higher incidence of frontal hematomas and slightly higher perinatal lethality (PubMed:12215548).|||N-glycosylated.|||Receptor for lysophosphatidic acid (LPA) (PubMed:11087877, PubMed:18066075). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins (PubMed:8922387, PubMed:9600933, PubMed:11040035, PubMed:18157949, PubMed:18066075, PubMed:23478264). Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels (PubMed:11040035, PubMed:12215548). Signaling triggers an increase of cytoplasmic Ca(2+) levels (PubMed:12215548). Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate (PubMed:11040035, PubMed:12215548, PubMed:23478264). Signaling mediates activation of down-stream MAP kinases (PubMed:11040035). Contributes to the regulation of cell shape (PubMed:8922387, PubMed:9600933, PubMed:11040035, PubMed:11087877). Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction (PubMed:9600933, PubMed:11040035, PubMed:12181339). Promotes the activation of Rho and the formation of actin stress fibers (PubMed:9600933, PubMed:12215548). Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1 (PubMed:23478264). Through its function as LPA receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding (PubMed:11087877, PubMed:18066075, PubMed:23478264). Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14 (PubMed:21821728). Promotes cell proliferation in response to LPA (PubMed:9600933, PubMed:11087877, PubMed:12215548, PubMed:18157949, PubMed:17692995, PubMed:23478264). Inhibits the intracellular ciliogenesis pathway in response to LPA and through AKT1 activation (By similarity). Required for normal skeleton development (PubMed:21569876). May play a role in osteoblast differentiation (PubMed:21569876). Required for normal brain development (PubMed:17656621, PubMed:18708146). Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus (PubMed:18708146). Plays a role in pain perception and in the initiation of neuropathic pain (PubMed:15195086, PubMed:19689455).|||Up-regulated by bacterial lipopolysaccharide (LPS) (at protein level). Up-regulated by bacterial lipopolysaccharide (LPS). http://togogenome.org/gene/10090:Qtrt2 ^@ http://purl.uniprot.org/uniprot/A0A5F8MPN7|||http://purl.uniprot.org/uniprot/B8ZXI1|||http://purl.uniprot.org/uniprot/Z4YJE9 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the queuine tRNA-ribosyltransferase family. QTRT2 subfamily.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Expressed in brain, heart, kidney, liver, lung, skeletal muscle, spleen and testis.|||Heterodimer of a catalytic subunit QTRT1 and an accessory subunit QTRT2.|||Major isoform in adult tissues.|||Mitochondrion outer membrane|||Non-catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine). http://togogenome.org/gene/10090:Rbm25 ^@ http://purl.uniprot.org/uniprot/B2RY56 ^@ Domain|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Aberrant splicing.|||Cytoplasm|||Interacts with LUC7L3 and SRRM1 (By similarity). Specifically associates with functional splicing complexes, including Sm proteins and U1, U2, U4, U5 and U6 snRNAs (By similarity). Associates with exon junction complex (EJC) proteins, including APEX1, DDX39B, NCBP1, RBM8A and RNPS1. Interaction with NCBP1 is RNA-dependent (By similarity).|||Nucleus speckle|||Probable cloning artifact.|||RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5'-splice site (5'-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5'-ss usage through the 5'-CGGGCA-3' RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5' ss in a 5'-CGGGCA-3'-dependent manner. Binds to the exonic splicing enhancer 5'-CGGGCA-3' RNA sequence located within exon 2 of the BCL2L1 pre-mRNA (By similarity).|||Sumoylated.|||The PWI domain binds nucleic acids with significant help from its N-terminal flanking basic region. It has an equal preference for binding to single- or double-stranded species, and it contributes to RBM25 role in modulation of alternative splicing, maybe by mediating RNA-dependent association with LUC7L3 (By similarity). http://togogenome.org/gene/10090:Grtp1 ^@ http://purl.uniprot.org/uniprot/Q9D3N8 ^@ Developmental Stage|||Function|||Tissue Specificity ^@ Highly expressed in testes, expression greatly increased at postnatal day 20 and remained high up to day 90. Moderately expressed in kidney and liver, weakly expressed in intestine, lung, ovaries and stomach. Expression of Growth hormone increased the expression in testis but decreased expression in liver and kidney.|||May act as a GTPase-activating protein for Rab family protein(s).|||Weakly expressed in the testis of the embryo and neonate. http://togogenome.org/gene/10090:Mib2 ^@ http://purl.uniprot.org/uniprot/Q8R516 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors.|||Endosome|||Highly expressed in brain, heart, liver and kidney.|||Highly expressed in neonate and adult, but only slightly in embryos. In 10.5 dpc embryos, it is weakly expressed in the tail bud and limb buds. Expressed in the same pattern than MIB1 in the skin and intestine at postnatal day 1 (P1) and in the hair follicle in the skin in the adult.|||Interacts with actin monomer.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Ubiquitinated. Possibly via autoubiquitination. http://togogenome.org/gene/10090:Trub2 ^@ http://purl.uniprot.org/uniprot/H3BKT7|||http://purl.uniprot.org/uniprot/Q91WG3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pseudouridine synthase TruB family.|||Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA.|||Minor enzyme contributing to the isomerization of uridine to pseudouridine (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs) such as COXI and COXIII mt-mRNAs. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation. Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs.|||Mitochondrion matrix http://togogenome.org/gene/10090:Mex3d ^@ http://purl.uniprot.org/uniprot/D3YTR3|||http://purl.uniprot.org/uniprot/Q3UE17 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Binds RNA through its KH domains.|||Cytoplasm|||Nucleus|||RNA binding protein, may be involved in post-transcriptional regulatory mechanisms. http://togogenome.org/gene/10090:Tbc1d9b ^@ http://purl.uniprot.org/uniprot/Q5SVR0 ^@ Domain|||Function|||Subcellular Location Annotation ^@ May act as a GTPase-activating protein for Rab family protein(s).|||Membrane|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site. http://togogenome.org/gene/10090:Ube4b ^@ http://purl.uniprot.org/uniprot/Q3V426|||http://purl.uniprot.org/uniprot/Q9ES00 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin conjugation factor E4 family.|||Cytoplasm|||Expressed predominantly in neuronal tissues. Also detected in liver, heart, brain, kidney and testis.|||In strain C57BL/Ola, a 85 kb region on chromosome 4 containing Nmnat1 and Ube4b is triplicated. Ube4b becomes linked to Nmnat1 and encodes a fusion protein located in the nucleus which is responsible for the delayed Wallerian degeneration of injured axons in C57BL/Ola.|||Interacts with VCP (PubMed:12504083). Interacts with STUB1/CHIP and UNC45B (By similarity).|||Nucleus|||Proteolytically cleaved by caspases during apoptosis. Cleaved efficiently at Asp-123 by caspase-6 and granzyme B. Cleaved with approximately 10-fold less efficiency at Asp-109 by caspase-3 and caspase-7 (By similarity).|||The U-box domain is required for the ubiquitin protein ligase activity.|||Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (PubMed:11435423). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (By similarity).|||Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. Also functions as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates. http://togogenome.org/gene/10090:Ctnnbl1 ^@ http://purl.uniprot.org/uniprot/Q9CWL8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing (By similarity). Participates in AID/AICDA-mediated somatic hypermutation (SHM) and class-switch recombination (CSR), 2 processes resulting in the production of high-affinity, mutated isotype-switched antibodies (PubMed:20585033).|||Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly with CWC15 and CDC5L in the complex. Interacts with AICDA; the interaction is important for the antibody diversification activity of AICDA. Interacts with PRPF31 (via its NLS). Interacts (via its N-terminal NLS) with KPNA1 and KPNA2 (By similarity).|||Nucleus|||The surface residues of the concave side of the superhelical ARM repeat region contribute to, but are not essential for NLS binding. http://togogenome.org/gene/10090:Retsat ^@ http://purl.uniprot.org/uniprot/Q64FW2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the carotenoid/retinoid oxidoreductase family. CrtISO subfamily.|||Catalyzes the saturation of all-trans-retinol to all-trans-13,14-dihydroretinol (PubMed:15358783, PubMed:17253779, PubMed:19139408). Does not exhibit any activity toward all-trans-retinoic acid, nor 9-cis, 11-cis or 13-cis-retinol isomers (PubMed:15358783). May play a role in the metabolism of vitamin A (PubMed:15358783, PubMed:17253779). Independently of retinol conversion, may regulate liver metabolism upstream of MLXIPL/ChREBP (PubMed:28855500). Required for adipocyte differentiation in a 3T3-L1 cell culture model (PubMed:19139408). This effect seems not to mimic the in vivo situation in which animals show increased adiposity in the absence of RETSAT (PubMed:19940255).|||Endoplasmic reticulum membrane|||Knockout mice fed either low-fat or high-fat (HFD) diets gain weight at a similar rate as their wild-type littermates and show normal insulin resistance and glucose tolerance. However, they exhibit increased adiposity and increased expression of key adipogenic markers, including PPAR-gamma and its target adipocyte P2 (aP2/FABP4), while maintained on an HFD.|||Predominantly expressed in the liver (at protein level) (PubMed:19940255). Also expressed at high levels in kidney, intestine, and white fat and brown fat (PubMed:15358783, PubMed:18289917, PubMed:19139408, PubMed:28855500). Weakly expressed in heart, skeletal muscle and testis and barely detected in the lung, brain and spleen (PubMed:15358783, PubMed:18289917, PubMed:28855500). Up-regulated in the liver of diet-induced obese mice, compared to lean animals (PubMed:28855500). Down-regulated in adipose tissue of obese mice; this decrease could be due to the impact of inflammatory cells on adipocytes (PubMed:19139408).|||Up-regulated during adipocyte differentiation in a 3T3-L1 cell culture model (at protein level).|||Up-regulated during starvation (PubMed:18289917). Up-regulated by PPARG (PubMed:19139408). http://togogenome.org/gene/10090:Eif1 ^@ http://purl.uniprot.org/uniprot/P48024|||http://purl.uniprot.org/uniprot/Q4V9T8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SUI1 family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. Together with eIF1A (EIF1AX), EIF1 facilitates scanning and is essential for start codon recognition on the basis of AUG nucleotide context and location relative to the 5'-cap. Participates to initiation codon selection by influencing the conformation of the 40S ribosomal subunit and the positions of bound mRNA and initiator tRNA; this is possible after its binding to the interface surface of the platform of the 40S ribosomal subunit close to the P-site. Together with eIF1A (EIF1AX), also regulates the opening and closing of the mRNA binding channel, which ensures mRNA recruitment, scanning and the fidelity of initiation codon selection. Continuously monitors and protects against premature and partial base-pairing of codons in the 5'-UTR with the anticodon of initiator tRNA. Together with eIF1A (EIF1AX), acts for ribosomal scanning, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. Interacts with EIF4G1, which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site. EIF4G1-EIF1 complex promotes ribosome scanning (on both short and long 5'UTR), leaky scanning (on short 5'UTR) which is the bypass of the initial start codon, and discrimination against cap-proximal AUG. Is probably maintained within the 43S PIC in open conformation thanks to eIF1A-EIF5 interaction. Once the correct start codon is reached, EIF1 is physically excluded from the decoding site, shifting the PIC into the closed conformation and arresting it at the start codon.|||Component of the 43S pre-initiation complex (43S PIC), which is composed of the 40S ribosomal subunit, EIF1, eIF1A (EIF1AX), eIF3 complex, EIF5 and eIF2-GTP-initiator tRNA complex (eIF2 ternary complex). Interacts with EIF4G1; in specific 5'-UTR length and AUG context. Interacts with EIF5; which in a mutual exclusive interaction associates either with EIF1 or with EIF2S2 on a common binding site. Interacts with RENT2.|||Cytoplasm http://togogenome.org/gene/10090:Ipp ^@ http://purl.uniprot.org/uniprot/P28575 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression seems confined to tissues derived from trophectoderm and primitive endoderm.|||May play a role in organizing the actin cytoskeleton.|||cytoskeleton http://togogenome.org/gene/10090:Frmd5 ^@ http://purl.uniprot.org/uniprot/Q6P5H6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CTNND1, ITGB5 (via cytoplasmic domain) and ROCK1.|||May be involved in regulation of cell migration. May regulate cell-matrix interactions via its interaction with ITGB5 and modifying ITGB5 cytoplasmic tail interactions such as with FERMT2 and TLN1. May regulate ROCK1 kinase activity possibly involved in regulation of actin stress fiber formation.|||adherens junction http://togogenome.org/gene/10090:Zswim6 ^@ http://purl.uniprot.org/uniprot/Q80TB7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Tissue Specificity ^@ Knockout animals born in Mendelian ratios, but show increased neonatal mortality such that around 40% survive to weaning. Mutants show a reduction in striatal volume and changes in medium spiny neuron morphology. They have alterations in motor control, including hyperactivity, impaired rotarod performance, repetitive movements, and behavioral hyperresponsiveness to amphetamine.|||Mouse embryos and newborn mice shown expression in the central nervous system (at protein level).|||Widely expressed during embryonic brain development but becomes restricted to the striatum postnatally (PubMed:28433741). Detected in the subventricular zone of the ganglionic eminences at 12.5 dpc. Higher expression levels appear in the lateral ganglionic eminence than in the medial ganglionic eminence. By 14.5 dpc expression remains enriched in the subventricular zone and marginal zones of the ganglionic eminences and is detected at low levels in the cortical plate, developing amygdala, and thalamus. By 16.5 dpc, expression increases in the cortical plate, developing amygdala, and portions of the thalamus and hypothalamus. In the telencephalon, the postnatal expression become more restricted to the striatum (PubMed:28433741).|||involved in nervous system development, important for striatal morphology and motor regulation. http://togogenome.org/gene/10090:Cyb5r2 ^@ http://purl.uniprot.org/uniprot/Q3KNK3 ^@ Function|||Similarity ^@ Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction. Responsible for NADH-dependent lucigenin chemiluminescence in spermatozoa by reducing both lucigenin and 2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt (WST-1) (By similarity). http://togogenome.org/gene/10090:Fzd8 ^@ http://purl.uniprot.org/uniprot/Q61091 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor Fz/Smo family.|||Cell membrane|||Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1 (By similarity). Interacts (via the PDZ-binding motif) with GPOC (via its PDZ domain). Interacts with RSPO1 and RSPO3. Interacts with glypican GPC3 (By similarity).|||Expressed in chondrocytes.|||Golgi apparatus|||Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.|||Membrane|||Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes (By similarity). The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.|||The FZ domain is involved in binding with Wnt ligands.|||Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Pag1 ^@ http://purl.uniprot.org/uniprot/Q3U1F9 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Mice are viable and do not show any developmental defect up to 20 months of age. They have normal T-cell development and normal T- and B-cell responses.|||Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. Inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins. May be involved in cell adhesion signaling.|||Palmitoylated.|||Phosphorylated by FYN on Tyr-314 in resting T-cells; which promotes interaction with CSK. Dephosphorylated by PTPRC/CD45 upon TCR activation; which leads to CSK dissociation. May also be dephosphorylated by PTPN11. Hyperphosphorylated in mast cells upon FCER1 activation.|||Present in T-cells (at protein level).|||When phosphorylated, interacts with CSK. Interacts with NHERF1/EBP50. In resting T-cells, part of a PAG1-NHERF1-MSN complex which is disrupted upon TCR activation. http://togogenome.org/gene/10090:Btg1 ^@ http://purl.uniprot.org/uniprot/P62325|||http://purl.uniprot.org/uniprot/Q3UEG0 ^@ Function|||Similarity|||Subunit ^@ Anti-proliferative protein.|||Belongs to the BTG family.|||Interacts with CNOT7 and CNOT8. http://togogenome.org/gene/10090:Ggnbp1 ^@ http://purl.uniprot.org/uniprot/D3Z3W4|||http://purl.uniprot.org/uniprot/Q6K1E7 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Golgi apparatus|||Induces mitochondrial fragmentation, possibly by promoting DNM1L-dependent fission and may play a role in mitochondrial morphogenesis during spermatogenesis.|||Interacts with isoform 1 and isoform 2 of GGN.|||Membrane|||Mitochondrion intermembrane space|||Specifically expressed in germ cells tightly related to meiosis. In the developing mouse testis, it is not detected in the testes of 14-day-old mice, when pachytene spermatocytes are still in their early stage, while it is detected in tubules with late pachytene spermatocytes and spermatids in the testes of 21-day-old mice.|||Testis-specific. In the testis, expressed only in germ cells and not in somatic cells. Expression starts in late primary spermatocytes in stage X-XII tubules and gradually increases towards step 1-3 spermatids in stage I-III tubules. Expression then declines continuously and disappears after step 7 spermatids in stage VII tubules (at protein level).|||The N-terminal domain is required for targeting to the mitochondrion. http://togogenome.org/gene/10090:Adat2 ^@ http://purl.uniprot.org/uniprot/Q6P6J0 ^@ Function|||Similarity ^@ Belongs to the cytidine and deoxycytidylate deaminase family. ADAT2 subfamily.|||Probably participates in deamination of adenosine-34 to inosine in many tRNAs. http://togogenome.org/gene/10090:Kcnj13 ^@ http://purl.uniprot.org/uniprot/P86046 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ13 subfamily.|||Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ13 has a very low single channel conductance, low sensitivity to block by external barium and cesium, and no dependence of its inward rectification properties on the internal blocking particle magnesium (By similarity).|||Membrane|||Phosphorylation at Ser-287 by PKA increases ionic currents. http://togogenome.org/gene/10090:Ikzf3 ^@ http://purl.uniprot.org/uniprot/O08900 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Ikaros C2H2-type zinc-finger protein family.|||C2H2-type 5 and C2H2-type 6 mediate homodimerization and heterodimerization.|||Cytoplasm|||Expression is restricted to lymphoid tissues. Expressed at highest levels in spleen and at lower levels in the thymus and bone marrow. First detected in more committed lymphoid progenitors and strongly up-regulated as these differentiate into pre-T and pre-B cell precursors.|||Homodimer. Heterodimer with other IKAROS family members. Interacts with IKZF4 and IKZF5. Interacts with HRAS. Interacts with FOXP3; this interaction may be required for silencing target genes and regulating the suppressive activity of FOXP3-positive regulatory T-cells (Treg). Interacts with BCL21L isoform Bcl-X(L); this interaction blocks the anti-apoptotic role of BCL21L. Associates with histone deacetylase complexes containing HDAC1, MTA2 and SIN3A (By similarity). Interacts with IKZF1.|||Nucleus|||Transcription factor that plays an important role in the regulation of lymphocyte differentiation. Binds to GGGAA. Plays an essential role in regulation of B-cell differentiation, proliferation and maturation to an effector state. Involved in regulating BCL2 expression and controlling apoptosis in T-cells in an IL2-dependent manner. http://togogenome.org/gene/10090:Btnl1 ^@ http://purl.uniprot.org/uniprot/Q7TST0 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Aberrant splicing.|||Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Membrane http://togogenome.org/gene/10090:Prl6a1 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0L9|||http://purl.uniprot.org/uniprot/O35257 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed in both placenta and decidual tissues. Detected first in deciduals cells early in gestation and in trophoblasts later in pregnancy.|||Increased gradually from days 8-12 and decrease to low levels by days 16.|||Secreted http://togogenome.org/gene/10090:Zp1 ^@ http://purl.uniprot.org/uniprot/Q059L1|||http://purl.uniprot.org/uniprot/Q62005 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZP domain family. ZPB subfamily.|||Cell membrane|||Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP1 ensures the structural integrity of the zona pellucida.|||Expressed in oocytes.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Not detected in resting oocytes. As oocytes begin to grow, levels increase to reach a maximum in midsized oocytes. Levels decrease in later stages of oocyte growth.|||O-glycosylated.|||Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers. Interacts with ZP3.|||Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida.|||The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.|||Zona pellucida http://togogenome.org/gene/10090:Csf2ra ^@ http://purl.uniprot.org/uniprot/Q00941 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 5 subfamily.|||Heterodimer of an alpha and a beta subunit. The beta subunit is common to the IL3, IL5 and GM-CSF receptors. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits (By similarity).|||Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Clk2 ^@ http://purl.uniprot.org/uniprot/F8WHX0|||http://purl.uniprot.org/uniprot/O35491 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) inhibits autophosphorylation. TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.|||Autophosphorylates on all three types of residues. Phosphorylation on Ser-34 and Thr-127 by AKT1 is induced by ionizing radiation or insulin. Phosphorylation plays a critical role in cell proliferation following low dose radiation and prevents cell death following high dose radiation. Phosphorylation at Thr-343 by PKB/AKT2 induces its kinase activity which is required for its stability. The phosphorylation status at Ser-141 influences its subnuclear localization; inhibition of phosphorylation at Ser-141 results in accumulation in the nuclear speckle.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily.|||By insulin (at protein level).|||Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Phosphorylates PAGE4 at several serine and threonine residues and this phosphorylation attenuates the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (By similarity).|||Interacts with RBMX and UBL5 (By similarity). Interacts with AKT1.|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Nup85 ^@ http://purl.uniprot.org/uniprot/Q8R480 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleoporin Nup85 family.|||Component of the nuclear pore complex (NPC). Component of the NPC Nup107-160 subcomplex, consisting of at least NUP107, NUP98/Nup96, NUP160, NUP133, NUP85, NUP37, NUP43 and SEC13. Interacts with NUP160, NUP133 and SEC13 (PubMed:12718872). Interacts with NUP37, NUP107 and NUP43. Interacts with CCR2.|||Cytoplasm|||Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance. As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP96/Nup98 and NUP153 to the nucleus. The Nup107-160 complex seems to be required for spindle assembly during mitosis. NUP85 is required for membrane clustering of CCL2-activated CCR2. Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol 3-kinase-Rac-lammellipodium protrusion cascade. Involved in nephrogenesis.|||Nucleus membrane|||kinetochore|||nuclear pore complex|||spindle http://togogenome.org/gene/10090:Ik ^@ http://purl.uniprot.org/uniprot/Q9Z1M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RED family.|||Chromosome|||Component of the spliceosome B complex. Interacts with SMU1. Interacts with MAD1L1. May interact with DHX15.|||Involved in pre-mRNA splicing as a component of the spliceosome. Auxiliary spliceosomal protein that regulates selection of alternative splice sites in a small set of target pre-mRNA species. Required for normal mitotic cell cycle progression. Recruits MAD1L1 and MAD2L1 to kinetochores, and is required to trigger the spindle assembly checkpoint. Required for normal accumulation of SMU1.|||Nucleus|||Ubiquitous.|||nucleoplasm|||spindle pole http://togogenome.org/gene/10090:Ints5 ^@ http://purl.uniprot.org/uniprot/Q8CHT3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 5 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Cytoplasm|||Nucleus|||Nucleus membrane http://togogenome.org/gene/10090:Lancl1 ^@ http://purl.uniprot.org/uniprot/O89112 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LanC-like protein family.|||Cell membrane|||Cytoplasm|||Detected in spinal cord (at protein level). Ubiquitous. Strongly expressed in brain, testis, alveolar macrophages and epithelial cells of the lung, kidney and intestine (PubMed:17305318, PubMed:9714732). Expression in brain increases during the first postnatal month and remaining high in adult (PubMed:25158856).|||Functions as glutathione transferase (PubMed:25158856). Catalyzes conjugation of the glutathione (GSH) to artificial substrates 1-chloro-2,4-dinitrobenzene (CDNB) and p-nitrophenyl acetate (PubMed:25158856). Mitigates neuronal oxidative stress during normal postnatal development and in response to oxidative stresses probably through GSH antioxidant defense mechanism (PubMed:25158856). May play a role in EPS8 signaling. Binds glutathione (By similarity).|||Induced by oxidative stress.|||Interacts with the C-terminal of STOM (By similarity). Interacts with the EPS8 SH3 domain. Interaction with EPS8 is inhibited by glutathione binding (By similarity).|||Knockout mice are viable. During later postnatal development, mice demonstrate prominent neuronal degeneration.|||Was originally thought to be a G-protein coupled receptor. http://togogenome.org/gene/10090:Btbd17 ^@ http://purl.uniprot.org/uniprot/Q9DB72 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Enpp3 ^@ http://purl.uniprot.org/uniprot/Q6DYE8 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Binds 2 zinc ions per subunit.|||Cell membrane|||Detected at the tip of villi in the small intestine (PubMed:28225814). Detected on basophils and mast cells (at protein level) (PubMed:25692702). Detected in the epithelial layer of the small intestine; expression is higher in the proximal part and lower in the distal part of the small intestine (PubMed:28225814).|||Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (By similarity). Limits mast cell and basophil responses during inflammation and during the chronic phases of allergic responses by eliminating the extracellular ATP that functions as signaling molecule and activates basophils and mast cells and induces the release of inflammatory cytokines (PubMed:25692702). Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (PubMed:28225814). Has also alkaline phosphodiesterase activity (By similarity).|||In bone marrow-derived mast cells and basophils, induced by activation of the high affinity immunoglobulin epsilon receptor 1 (Fc epsilon RI).|||Mice appear healthy, and have normal numbers of peripheral lymphocytes, eosinophils and neutrophils. Basophil numbers are normal in bone marrow, but are markedly increased in peripheral blood and spleen. Likewise, mutant mice have an increased number of mast cells in the small and large intestine. Both mast cells and basophils show increased proliferation in response to extracellular ATP. Mutant mice display normal immediate reaction to allergens, but strongly increased chronic allergic inflammation in skin, intestine and lung that lead to severe tissue damage. Extracellular ATP levels are normal in the absence of allergen, and strongly increased after exposure to allergen, due to impaired clearance of extracellular ATP (PubMed:25692702). Mutant mice display increased levels of extracellular ATP in the lumen of the small intestine. They have decreased numbers of plasmacytoid dendritic cells in the small intestine lamia propria and in Peyer patches; the decrease is due to increased ATP levels that cause increased apoptosis of plasmacytoid dendritic cells (PubMed:28225814).|||Monomer and homodimer.|||N-glycosylated. N-glycosylation is necessary for normal transport to the cell membrane, but is not the apical targeting signal.|||Secreted http://togogenome.org/gene/10090:Carnmt1 ^@ http://purl.uniprot.org/uniprot/Q80UY1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the carnosine N-methyltransferase family.|||Homodimer. Each monomer accommodates one molecule of carnosine in its active pocket, precisely anchoring the histidine imidazole ring such that only N1 is exposed and deprotonated for methylation.|||N-methyltransferase that catalyzes the formation of anserine (beta-alanyl-N(Pi)-methyl-L-histidine) from carnosine. Anserine, a methylated derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of vertebrate skeletal muscles. Also methylates other L-histidine-containing di- and tripeptides such as Gly-Gly-His, Gly-His and homocarnosine (GABA-His).|||Nucleus|||The Gly-Xaa-Gly-Xaa-Gly (GXGXG) motif binds the adenosyl part of S-adenosyl-L-methionine.|||The carnosine-binding region forms hydrophobic and hydrogen bonds with carnosine, defining a flipping orientation of the imidazole ring so that N1 is present next to S-adenosyl-L-methionine for methylation.|||cytosol http://togogenome.org/gene/10090:Grwd1 ^@ http://purl.uniprot.org/uniprot/Q5XJZ3|||http://purl.uniprot.org/uniprot/Q810D6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Histone binding-protein that regulates chromatin dynamics and minichromosome maintenance (MCM) loading at replication origins, possibly by promoting chromatin openness.|||Interacts with METTL18. Interacts with CDT1; origin binding of GRWD1 is dependent on CDT1. Interacts with CDC6; origin binding of GRWD1 is dependent on CDC6. Binds to histone H2A-H2B and H3-H4 complexes.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Lamc2 ^@ http://purl.uniprot.org/uniprot/G5E874 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||basement membrane http://togogenome.org/gene/10090:Ints13 ^@ http://purl.uniprot.org/uniprot/Q8QZV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the asunder family.|||Crucial regulator of the mitotic cell cycle and development. At prophase, required for dynein anchoring to the nuclear envelope important for proper centrosome-nucleus coupling. At G2/M phase, may be required for proper spindle formation and execution of cytokinesis. Probable component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing.|||Cytoplasm|||Interacts with PAFAH1B1; this interaction may be required for proper recruitment of dynein complexes to the nuclear envelope at prophase.|||Nucleus http://togogenome.org/gene/10090:Scgb2b26 ^@ http://purl.uniprot.org/uniprot/Q8JZX1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Rtp2 ^@ http://purl.uniprot.org/uniprot/Q80ZI2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM7 family.|||Cell membrane|||Interacts with olfactory receptors.|||Predominantly expressed in olfactory and vomeronasal organs, in mature olfactory sensory neurons.|||Specifically promotes functional cell surface expression of olfactory receptors, but not of other GPCRs. http://togogenome.org/gene/10090:Spef1 ^@ http://purl.uniprot.org/uniprot/Q99JL1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Cytoplasm|||Depletion in ependymal cells by RNAi completely abolishes the central pair microtubules and markedly attenuates ciliary localizations of HYDIN and SPAG6, resulting in rotational beat of the ependymal cilia.|||Expressed predominantly in the seminiferous epithelium of adult testis (PubMed:15979255). Expressed in pillar cells of the organ of Corti (at protein level). Expressed in brain, kidney, lung and testis (PubMed:16206169, PubMed:30535028). Highly expressed in the trachea, lung and oviduct (PubMed:30535028).|||Expression is first detected in the testis at 3 weeks and continues to adulthood.|||Homodimer (PubMed:30535028). Interacts with actin, TJP1, CGN and CDH1 (By similarity).|||Microtubule-associated protein that promotes microtubule bundling and stabilizes microtubules against depolymerization in response to cold shock (PubMed:16206169). Microtubule-associated protein involved in the stabilization of microtubules along the axis of migration during radial intercalation. Promotes the establishment and stabilization of an axis of microtubules required for the active migration of cells into the outer epithelium (By similarity). Essential for ciliary central apparatus formation which requires both its microtubule-binding and bundling activities and for ciliary localization of HYDIN and SPAG6 in ependymal cilia (PubMed:30535028). Binds actin in intestinal epithelial cells (IECs), essential for IECs survival and contributes to formation of filopodia and lamellipodia in migrating IECs (By similarity). Regulates planar cell polarity signaling pathway and asymmetric microtubule accumulation in ciliated epithelia (By similarity).|||Radial intercalation is a developmentally reiterated form of migration by which cells move in a direction orthogonal to the plane of the tissue from an inner layer to an outer layer.|||The Calponin-homology domain mediates its binding to microtubules.|||cilium axoneme|||filopodium|||flagellum|||lamellipodium|||microvillus|||stress fiber http://togogenome.org/gene/10090:Or52s19 ^@ http://purl.uniprot.org/uniprot/A2RS33 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r225 ^@ http://purl.uniprot.org/uniprot/Q8R2A5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gtpbp4 ^@ http://purl.uniprot.org/uniprot/Q99ME9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with pre-60S ribosomal particles. Interacts with MINAS-60 (product of an alternative open reading frame of RBM10).|||Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. NOG subfamily.|||Involved in the biogenesis of the 60S ribosomal subunit. Acts as TP53 repressor, preventing TP53 stabilization and cell cycle arrest.|||Ubiquitous.|||nucleolus http://togogenome.org/gene/10090:Kif16b ^@ http://purl.uniprot.org/uniprot/B1AVY7 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Cytoplasm|||Early endosome membrane|||Embryonic death. Embryos are arrested at the blastocyst stage: the primitive endoderm and epiblast cannot be distinguished and appear as cell clumps resembling the inner cell mass (ICM) of the blastocyst. Embryos do not develop an epiblast epithelium and the uterine reaction appears to be incomplete. Development of the primitive endoderm and a basement membrane derived from it are severely affected in embryos at 4.5 dpc.|||Interacts with PTPN21 (By similarity). Interacts with RAB14.|||Partially unspliced pre-RNA.|||Plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation. Regulates the plus end motility of early endosomes and the balance between recycling and degradation of receptors such as EGF receptor (EGFR) and FGF receptor (FGFR). Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development.|||The PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). Does not bind phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (By similarity).|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Mavs ^@ http://purl.uniprot.org/uniprot/Q8VCF0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter required for innate immune defense against viruses (PubMed:24037184). Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5) (PubMed:24037184). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (By similarity). Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response (By similarity). May activate the same pathways following detection of extracellular dsRNA by TLR3 (By similarity). May protect cells from apoptosis (By similarity). Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria (PubMed:23582325).|||Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with RIGI and IFIH1/MDA5 (By similarity).|||Both CARD and transmembrane domains are essential for antiviral function. The CARD domain is responsible for interaction with RIGI and IFIH1/MDA5.|||Following activation, phosphorylated by TBK1 at Ser-418 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines.|||Mitochondrion|||Mitochondrion outer membrane|||Peroxisome|||Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation. Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction.|||Self-associates and polymerizes (via CARD domains) to form 400 nM long three-stranded helical filaments on mitochondria, filament nucleation requires interaction with RIGI whose CARD domains act as a template for filament assembly (By similarity). Interacts with RIGI, IFIH1/MDA5, TRAF2, TRAF6 and C1QBP (By similarity). May interact with FADD, RIPK1, IKBKE, CHUK and IKBKB (By similarity). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By similarity). Interacts with NLRX1 (By similarity). Interaction with NLRX1 requires the CARD domain (By similarity). Interacts with PSMA7 (By similarity). Interacts with TRAFD1 (PubMed:18849341). Interacts (via C-terminus) with PCBP2 in a complex containing MAVS/IPS1, PCBP2 and ITCH (By similarity). Interacts with CYLD (By similarity). Interacts with SRC (By similarity). Interacts with DHX58/LGP2 and IKBKE (By similarity). Interacts with STING1 (By similarity). Interacts with IFIT3 (via N-terminus) (By similarity). Interacts with TBK1 only in the presence of IFIT3 (By similarity). Interacts with TTLL12; the interaction prevents MAVS binding to TBK1 and IKBKE (By similarity). Interacts with MUL1 (By similarity). Interacts with ANKRD17 (By similarity). Interacts with NDFIP1 (By similarity). Interacts with SMURF1; the interaction is mediated by NDFIP1 and leads to MAVS ubiquitination and degradation (PubMed:23087404). Interacts (via C-terminus) with GPATCH3; the interaction is markedly increased upon viral infection (By similarity). Directly interacts (via CARD domain) with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates (By similarity). Interacts with DHX33 (via the helicase C-terminal domain) (PubMed:24037184). Interacts with DDX3X (via C-terminus); this interaction may occur rapidly, but transiently after viral infection (By similarity). The interaction with DDX3X potentiates MAVS-mediated IFNB induction (By similarity). Conversely inhibition of this interaction prevents MAVS-mediated IFNB induction (By similarity). Transiently interacts with TRAF3 early during viral infection (By similarity). Interacts with CLPB (By similarity). Interacts with TRAF3IP3 (By similarity). Interacts with TOMM70; the interaction is enhanced by virus infection (By similarity). Interacts with ZNFX1 (PubMed:31685995). Interacts with DHX15 (By similarity). Interacts with N4BP3; this interaction promotes the polyubiquitination of MAVS (By similarity). Interacts with TAX1BP1; this interaction induces MAVS polyubiquitination (By similarity). Interacts with NLRP3; promoting NLRP3 recruitment to mitochondria and activation of the NLRP3 inflammasome (PubMed:23582325). Interacts with ECSIT; this interaction bridges RIGI to the MAVS complex at the mitochondrion (By similarity). Interacts with UBL7; this interaction promotes MAVS 'Lys-27'-linked ubiquitination leading to type I interferon production (By similarity).|||The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of MAVS recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines.|||The transmembrane domain and residues 285-420 are essential for its interaction with DHX58/LGP2.|||The transmembrane domain and residues 300-444 are essential for its interaction with DHX58/LGP2.|||Ubiquitinated. Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH; ITCH-dependent polyubiquitination is mediated by the interaction with PCBP2 and leads to MAVS/IPS1 proteasomal degradation. Ubiquitinated by RNF125, leading to its degradation by the proteasome. Undergoes 'Lys-48'-linked ubiquitination catalyzed by SMURF1. Ubiquitinated via 'Lys-63'-linked ubiquitination at Lys-10 by TRIM31, promoting MAVS polymerization and formation of three-stranded helical filaments on mitochondria. Undergoes 'Lys-63'-linked ubiquitination leading to enhanced interaction between MAVS and TRAF2. Undergoes 'Lys-27'-linked ubiquitination by TRIM21 leading to enhanced interaction between MAVS and TBK1 (By similarity). http://togogenome.org/gene/10090:Or1j12 ^@ http://purl.uniprot.org/uniprot/Q8VGL0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Serpinb9f ^@ http://purl.uniprot.org/uniprot/Q80UK5 ^@ Similarity ^@ Belongs to the serpin family. Ov-serpin subfamily. http://togogenome.org/gene/10090:Or4a76 ^@ http://purl.uniprot.org/uniprot/L7MU51 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ugdh ^@ http://purl.uniprot.org/uniprot/O70475|||http://purl.uniprot.org/uniprot/Q3TS38 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the UDP-glucose/GDP-mannose dehydrogenase family.|||Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:9737970). Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (PubMed:14505572). Required for proper brain and neuronal development (By similarity).|||Detected in embryos from 7.5 to 17.5 dpc (PubMed:9737970, PubMed:14505572). Detected in the epiblast at 7.5 dpc, in the cardiac region and tail bud at 8.5 dpc, in otic vesicle and branchial arches at 9.5 dpc, and in forebrain, branchial arches and limb buds at 10.5 dpc (PubMed:14505572).|||Homohexamer.|||Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.|||The allosteric switch region moves by about 5 Angstroms when UDP-xylose is bound, and occupies part of the UDP-glucose binding site. At the same time it promotes domain movements that disrupt the active hexameric ring structure and lead to the formation of a horseshoe-shaped, inactive hexamer.|||The protein goes through several conformation states during the reaction cycle, giving rise to hysteresis. In the initial state, the ligand-free protein is in an inactive conformation (E*). Substrate binding triggers a change to the active conformation (E). UDP-xylose binding triggers the transition to a distinct, inhibited conformation. The presence of an intrinsically disordered C-terminus promotes a more dynamic protein structure and favors a conformation with high affinity for UPD-xylose.|||UDP-alpha-D-xylose (UDX) acts as a feedback inhibitor (PubMed:9737970). It binds at the same site as the substrate, but functions as allosteric inhibitor by triggering a conformation change that disrupts the active hexameric ring structure and gives rise to an inactive, horseshoe-shaped hexamer (By similarity). http://togogenome.org/gene/10090:Tpm2 ^@ http://purl.uniprot.org/uniprot/A2AIM4|||http://purl.uniprot.org/uniprot/P58774|||http://purl.uniprot.org/uniprot/Q61344|||http://purl.uniprot.org/uniprot/Q6PJ18|||http://purl.uniprot.org/uniprot/Q9D1R6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tropomyosin family.|||Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. The non-muscle isoform may have a role in agonist-mediated receptor internalization (PubMed:16094730).|||Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain.|||Phosphorylated on Ser-61 by PIK3CG. Phosphorylation on Ser-61 is required for ADRB2 internalization.|||The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.|||cytoskeleton http://togogenome.org/gene/10090:Ruvbl2 ^@ http://purl.uniprot.org/uniprot/Q3TXT7|||http://purl.uniprot.org/uniprot/Q9WTM5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RuvB family.|||Cytoplasm|||Dynein axonemal particle|||Forms homohexameric rings (Probable). Can form a dodecamer with RUVBL1 made of two stacked hexameric rings; however, even though RUVBL1 and RUVBL2 are present in equimolar ratio, the oligomeric status of each hexamer is not known. Oligomerization may regulate binding to nucleic acids and conversely, binding to nucleic acids may affect the dodecameric assembly. Interaction of the complex with DHX34 results in conformational changes of the N-terminus of the RUVBL2 subunits, resulting in loss of nucleotide binding ability and ATP hydrolysis of the complex (By similarity). Interacts with the transcriptional activation domain of MYC. Interacts with ATF2. Component of the RNA polymerase II holoenzyme complex. May also act to bridge the LEF1/TCF1-CTNNB1 complex and TBP. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. RUVBL2 interacts with EP400. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Interacts with NPAT. Component of the chromatin-remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with IGHMBP2. Interacts with TELO2. Interacts with HINT1. Component of a SWR1-like complex. Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with ITFG1. Interacts with ZMYND10. Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation. Forms a complex with APPL1 and APPL2 (By similarity). Interacts with ZNHIT2 (via HIT-type zinc finger) in the presence of ATP or ADP; shows a stronger interaction in the presence of ADP (By similarity). The RUVBL1/RUVBL2 complex interacts with ZNHIT1 (via HIT-type zinc finger), ZNHIT3 (via HIT-type zinc finger), ZNHIT6 (via HIT-type zinc finger) and DDX59/ZNHIT5 (via HIT-type zinc finger) in the presence of ADP (By similarity). Interacts with NOPCHAP1; the interaction is direct and disrupted upon ATP binding (By similarity). Interacts with SMG1 (By similarity).|||Membrane|||Nucleus|||Nucleus matrix|||Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (By similarity). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (By similarity). This modification may both alter nucleosome-DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (By similarity). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (By similarity). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (By similarity). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (By similarity). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (By similarity). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding (By similarity). Plays an essential role in oncogenic transformation by MYC and also modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex (By similarity). May also inhibit the transcriptional activity of ATF2 (By similarity). Involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway where it negatively regulates expression of ER stress response genes (By similarity). May play a role in regulating the composition of the U5 snRNP complex (By similarity).|||Proposed core component of the chromatin remodeling Ino80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding.|||nucleoplasm http://togogenome.org/gene/10090:Chtop ^@ http://purl.uniprot.org/uniprot/Q9CY57 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Asymmetrically methylated by PRMT1. Symmetrically methylated by PRMT5.|||Broadly expressed at 16.5 dpc.|||Broadly expressed with highest levels found in thymus, spleen, and lymph nodes. Expressed in an erythroid progenitor cell line derived from fetal liver.|||Interacts with PRMT1 and PRMT5 (PubMed:19858291, PubMed:22872859). Interacts with the 5FMC complex; the interaction is methylation-dependent. Interacts with FYTTD1, SET and PRC1 complex members CBX4, RNF2 and PHC2; the interactions are methylation-independent. Interacts with ZNF148 (PubMed:22872859). Interacts with WDR77 and ERH (By similarity).|||May be due to an intron retention.|||Nucleus|||Nucleus speckle|||Plays an important role in the ligand-dependent activation of estrogen receptor target genes (By similarity). May play a role in the silencing of fetal globin genes (PubMed:20688955). Recruits the 5FMC complex to ZNF148, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Required for the tumorigenicity of glioblastoma cells. Binds to 5-hydroxymethylcytosine (5hmC) and associates with the methylosome complex containing PRMT1, PRMT5, MEP50 and ERH. The CHTOP-methylosome complex associated with 5hmC methylates H4R3 and transactivates genes involved in glioblastomagenesis (PubMed:25284789).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Cdk20 ^@ http://purl.uniprot.org/uniprot/Q9JHU3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Involved in cell growth. Activates CDK2, a kinase involved in the control of the cell cycle, by phosphorylating residue 'Thr-160' (By similarity). Required for high-level Shh responses in the developing neural tube. Together with TBC1D32, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing GLI2 to be properly activated in response to SHH signaling.|||Monomer (By similarity). Interacts with MAK (By similarity). Interacts with TBC1D32.|||Nucleus|||cilium http://togogenome.org/gene/10090:Lair1 ^@ http://purl.uniprot.org/uniprot/Q8BG84 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in lymphoid organs and in cell lines of hemopoietic origin.|||Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells (By similarity).|||ITIM (immunoreceptor tyrosine-based inhibitor motif) motif is a cytoplasmic motif present in 2 copies in the intracellular part of LAIR1. When phosphorylated, ITIM motif can bind the SH2 domain of several SH2-containing phosphatases, leading to down-regulation of cell activation.|||Interacts with SH2 domains of tyrosine-protein phosphatases PTPN6 and PTPN11. The interaction with PTPN6 is constitutive. Interacts with the SH2 domain of CSK. Binds with high affinity to extracellular matrix collagens, the interaction is functionally important (By similarity).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||N-glycosylated.|||Phosphorylation at Tyr-228 and Tyr-257 activates it. May be phosphorylated by LCK (By similarity). http://togogenome.org/gene/10090:Cox10 ^@ http://purl.uniprot.org/uniprot/Q3U3N1|||http://purl.uniprot.org/uniprot/Q3UDN4|||http://purl.uniprot.org/uniprot/Q8CFY5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UbiA prenyltransferase family.|||Belongs to the ubiA prenyltransferase family.|||Converts protoheme IX and farnesyl diphosphate to heme O.|||Membrane|||Mitochondrion membrane http://togogenome.org/gene/10090:Pth2 ^@ http://purl.uniprot.org/uniprot/A0A1B0GR43|||http://purl.uniprot.org/uniprot/Q91W27 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the parathyroid hormone family.|||Expressed in testis and, less abundantly, in liver and kidney. Expressed in seminiferous tubuli and several brain regions, including nucleus ruber, caudal paralemniscal nucleus, nucleus centralis pontis, and nucleus subparafascicularis thalami. Expressed in neurons of cerebral cortex and subcortical areas. Expressed in Purkinje cells of cerebellum.|||Ligand of high affinity for the PTH2 receptor (PTH2R).|||Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation. Induces protein kinase C beta activation, recruitment of beta-arrestin and PTH2R internalization. May inhibit cell proliferation via its action of PTH2R activation. Neuropeptide which may also have a role in spermatogenesis. May activate nociceptors and nociceptive circuits.|||Secreted|||The N-terminal truncation of tuberoinfundibular peptide of 39 residues [TIP39(7-39)] reverses PTH2R/PTHR1 binding selectivity, then is a highly potent and selective antagonist for PTHR1. http://togogenome.org/gene/10090:Slc2a2 ^@ http://purl.uniprot.org/uniprot/P14246 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Cell membrane|||D-glucose and maltose competitively inhibit fructose transport. D-glucose, D-fructose and maltose inhibit deoxyglucose transport.|||Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose. Likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells; may comprise part of the glucose-sensing mechanism of the beta cell. May also participate with the Na(+)/glucose cotransporter in the transcellular transport of glucose in the small intestine and kidney. Also able to mediate the transport of dehydroascorbate.|||In embryo, expressed in endoderm layer of yolk sac and liver primordium.|||N-glycosylated; required for stability and retention at the cell surface of pancreatic beta cells. http://togogenome.org/gene/10090:Ldc1 ^@ http://purl.uniprot.org/uniprot/B7ZWH9|||http://purl.uniprot.org/uniprot/Q3UNZ2 ^@ Similarity ^@ Belongs to the Orn/Lys/Arg decarboxylase class-II family. http://togogenome.org/gene/10090:Inpp5f ^@ http://purl.uniprot.org/uniprot/Q8CDA1 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals develop normal corticospinal tract and raphespinal tract. Mutants show greater axonal growth and functional recovery after central nervous system trauma (PubMed:26203138). Knockout mice have normal cardiac form and function but show augmented hypertrophy and reactivation of the fetal gene program in response to stress compared to wild-type littermates (PubMed:19875726).|||Early endosome|||Highly expressed in brain and hypothalamus, expressed in lung and pancreas, and detected at low levels in liver and heart (at protein level).|||Homodimer (By similarity). Interacts with OCRL and RAB5. Interacts with INPP5B and INPP4A (PubMed:25869668). Interacts with STAT3; the interaction is independent of STAT3 'Tyr-705' phosphorylation status (By similarity).|||INPP5F has been initially described as an inositol polyphosphate 5-phosphatase.|||Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling (PubMed:25869668, PubMed:25869669). Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms (By similarity). Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus (By similarity). Functionally important modulator of cardiac myocyte size and of the cardiac response to stress (PubMed:19875726). May play a role as negative regulator of axon regeneration after central nervous system injuries (PubMed:26203138).|||Recycling endosome|||Up-regulated in the absence of histone deacetylase 2/HDAC2 in the heart from HDAC2-null mice.|||clathrin-coated pit http://togogenome.org/gene/10090:Wif1 ^@ http://purl.uniprot.org/uniprot/Q3TYU1|||http://purl.uniprot.org/uniprot/Q9WUA1 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.|||Expression highest in heart and lung. Lower in brain and eye.|||Interacts with MYOC.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Amfr ^@ http://purl.uniprot.org/uniprot/Q3TCI2|||http://purl.uniprot.org/uniprot/Q9R049 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ E3 ubiquitin-protein ligase that mediates the polyubiquitination of lysine and cysteine residues on target proteins, such as CD3D, CYP3A4, CFTR, INSIG1, SOAT2/ACAT2 and APOB for proteasomal degradation (PubMed:16987818, PubMed:18216283). Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD) (PubMed:16987818, PubMed:18216283). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG1 complex at the ER membrane (PubMed:22863805). In addition, interaction of AMFR with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced HMGCR ubiquitination (By similarity). The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction (By similarity). In addition to ubiquitination on lysine residues, catalyzes ubiquitination on cysteine residues: together with INSIG1, mediates polyubiquitination of SOAT2/ACAT2 at 'Cys-277', leading to its degradation when the lipid levels are low (By similarity). Catalyzes ubiquitination and subsequent degradation of INSIG1 when cells are depleted of sterols (By similarity). Mediates polyubiquitination of INSIG2 at 'Cys-215' in some tissues, leading to its degradation (By similarity). Also regulates ERAD through the ubiquitination of UBL4A a component of the BAG6/BAT3 complex (By similarity). Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation (By similarity). Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor (PubMed:12650607). In association with LMBR1L and UBAC2, negatively regulates the canonical Wnt signaling pathway in the lymphocytes by promoting the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (PubMed:31073040). Regulates NF-kappa-B and MAPK signaling pathways by mediating 'Lys-27'-linked polyubiquitination of TAB3 and promoting subsequent TAK1/MAP3K7 activation (By similarity).|||Endoplasmic reticulum membrane|||Expressed in heart, brain, liver, lung, skeletal muscle, kidney and testis. Not detected in spleen.|||Interacts with RNF5. Also forms an ERAD complex containing VCP/p97, NGLY1; PSMC1; SAKS1 and RAD23B required for coupling retrotranslocation, ubiquitination and deglycosylation. Interacts with DERL1. Interacts (through a region distinct from the RING finger) with UBE2G2/UBC7. Component of the VCP/p97-AMFR/gp78 complex that enhances VCP/p97 binding to polyubiquitinated proteins for their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway. Interacts (via the VIM) with VCP/p97. Interacts (via its membrane domain) with INSIG1; the interaction initiates the sterol-mediated ubiquitination and degradation of HMGCR by the ERAD pathway. Interacts with AUP1, UBE2G2 and RNF139/TRC8; interaction with AUP1 facilitates interaction of AMFR with ubiquitin-conjugating enzyme UBE2G2 and ubiquitin ligase RNF139, leading to sterol-induced ubiquitination of HNGCR and its subsequent proteasomal degradation (By similarity). Interacts with BAG6. Interacts with USP13 (via UBA 2 domain); the interaction is direct (By similarity). Interacts with LMBR1L, UBAC2 and CTNNB1 (PubMed:31073040). Interacts with C18orf32 (By similarity).|||Membrane|||Mice with a conditional deletion in the liver display improved hyperlipidemia and insulin resistance: mice show elevated energy expenditure and are resistant to diet-induced obesity and glucose intolerance (PubMed:22863805). Increased stability of Hmgcr, Insig1 and Insig2 and suppression of the SREBP pathway and novo lipid biosynthesis (PubMed:22863805).|||Palmitoylation of the RING-type zing finger by ZDHHC6 promotes localization to the peripheral endoplasmic reticulum.|||The CUE domain is required for recognition of misfolded proteins such as mutant CFTR.|||The VCP/p97-interacting motif (VIM) is sufficient for binding VCP/p97 to form a complex capable of transferring VCP/p97 from the cytosol to microsomes. http://togogenome.org/gene/10090:Kat6a ^@ http://purl.uniprot.org/uniprot/G3X940 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MYST (SAS/MOZ) family.|||Nucleus http://togogenome.org/gene/10090:Adamts10 ^@ http://purl.uniprot.org/uniprot/P58459 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Interacts with FBN1; this interaction promotes microfibrils assembly.|||May be due to intron retention.|||Metalloprotease that participate in microfibrils assembly. Microfibrils are extracellular matrix components occurring independently or along with elastin in the formation of elastic tissues (By similarity).|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||Widely expressed in adult tissues.|||Widely expressed throughout embryo development. Widespread expression in embryo until 12.5 days of gestation, after which it is then expressed in a more restricted fashion, with especially strong expression in developing lung, bone, and craniofacial region.|||extracellular matrix http://togogenome.org/gene/10090:Me3 ^@ http://purl.uniprot.org/uniprot/Q8BMF3 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the malic enzymes family.|||Divalent metal cations. Prefers magnesium or manganese.|||Mitochondrion matrix http://togogenome.org/gene/10090:Fmr1 ^@ http://purl.uniprot.org/uniprot/E9QAT0|||http://purl.uniprot.org/uniprot/Q547R0|||http://purl.uniprot.org/uniprot/Q6AXB7|||http://purl.uniprot.org/uniprot/Q8BPK8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FMR1 family.|||Cell membrane|||Cytoplasmic ribonucleoprotein granule|||Membrane|||Perikaryon|||Presynaptic cell membrane|||Stress granule|||Synapse|||Synaptic cell membrane|||axon|||centromere|||dendrite|||dendritic spine|||filopodium tip|||growth cone|||neuron projection|||nucleolus|||perinuclear region|||synaptosome http://togogenome.org/gene/10090:Tmem123 ^@ http://purl.uniprot.org/uniprot/Q91Z22 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CD164 family.|||Implicated in oncotic cell death, characterized by cell swelling, organelle swelling, vacuolization and increased membrane permeability.|||Membrane http://togogenome.org/gene/10090:Or52h2 ^@ http://purl.uniprot.org/uniprot/Q8VGW1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sult6b1 ^@ http://purl.uniprot.org/uniprot/P0CC03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Expressed in brain, heart, kidney, thymus, lung, liver and testis.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of thyroxine. Involved in the metabolism of thyroxine.|||cytosol http://togogenome.org/gene/10090:Med29 ^@ http://purl.uniprot.org/uniprot/Q9DB91 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 29 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Associates with the MED18/MED20 heteromer (By similarity).|||Nucleus http://togogenome.org/gene/10090:Rxfp4 ^@ http://purl.uniprot.org/uniprot/Q5Y985|||http://purl.uniprot.org/uniprot/Q7TQP4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected only in bone marrow.|||High affinity receptor for INSL5. Also acts as receptor for RLN3/relaxin-3, as well as bradykinin and kallidin. Binding of the ligand inhibit cAMP accumulation (By similarity).|||Membrane http://togogenome.org/gene/10090:Oxct2a ^@ http://purl.uniprot.org/uniprot/Q9JJN4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 3-oxoacid CoA-transferase family.|||Homodimer.|||Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity). Probably play and important roles in the energy metabolism of spermatozoa.|||Mitochondrion http://togogenome.org/gene/10090:Dpp8 ^@ http://purl.uniprot.org/uniprot/Q80YA7 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S9B family. DPPIV subfamily.|||Cytoplasm|||Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2 (By similarity). Acts as a key inhibitor of caspase-1-dependent monocyte and macrophage pyroptosis in resting cells by preventing activation of NLRP1 and CARD8 (PubMed:27820798, PubMed:29396289). Sequesters the cleaved C-terminal part of NLRP1 and CARD8, which respectively constitute the active part of the NLRP1 and CARD8 inflammasomes, in a ternary complex, thereby preventing their oligomerization and activation (By similarity). The dipeptidyl peptidase activity is required to suppress NLRP1 and CARD8; however, neither NLRP1 nor CARD8 are bona fide substrates of DPP8, suggesting the existence of substrate(s) required for NLRP1 and CARD8 inhibition (By similarity).|||Homodimer (By similarity). Forms a ternary complex with NLRP1, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of NLRP1 (NACHT, LRR and PYD domains-containing protein 1, C-terminus) (By similarity). Forms a ternary complex with CARD8, composed of a DPP8 homodimer, one full-length NLRP1 protein, and one cleaved C-terminus of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) (By similarity). In the ternary complex, only one subunit of the DPP8 homodimer is bound to NLRP1 or CARD8 (By similarity).|||Inhibited by zinc (By similarity). Inhibited by the serine proteinase inhibitor 4-(2-aminoethyl)benzenesulphonyl fluoride (AEBSF), and by di-isopropylfluorophosphate (By similarity). Specifically inhibited by isoindoline derivatives (By similarity). Inhibited by Val-boroPro (Talabostat, PT-100), a non-selective inhibitor, which triggers pyroptosis in monocytes and macrophages (PubMed:27820798, PubMed:29396289). http://togogenome.org/gene/10090:Tyr ^@ http://purl.uniprot.org/uniprot/P11344|||http://purl.uniprot.org/uniprot/Q91XK0 ^@ Cofactor|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tyrosinase family.|||Binds 2 copper ions per subunit.|||Defects in Tyr result in various forms of albinism. Himalayan strain tyrosinase is temperature-sensitive.|||Expressed in the skin.|||Forms an OPN3-dependent complex with DCT in response to blue light in melanocytes.|||Glycosylated.|||Melanosome|||Melanosome membrane|||This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds (PubMed:2517217). Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine (PubMed:2517217, PubMed:1537333, PubMed:35469906). In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone (PubMed:1537333). http://togogenome.org/gene/10090:Chek1 ^@ http://purl.uniprot.org/uniprot/O35280 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3 initiator methionines can be considered. If this isoform were to start at the first ATG, it would produce a 28 amino acid-long peptide, sharing the first 22 amino acids with the canonical sequence (isoform 1) and differing in the last 6 residues (VQLAVN -> ARHRDA). An initiation at this site could target the mRNA to nonsense-mediated mRNA decay and, in this case, the peptide would be produced at very low levels. The second possible translation initiation site would lead to the synthesis of the sequence shown in this entry as isoform 2. However, the Kozak sequence for this site is not optimal. Finally the third potential initiator methionine corresponds to position 167 in isoform 1 and would lead to the synthesis of a 310 amino acid-long protein identical to isoform 1 residues 167 through 476.|||Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication. Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B. Proteolytic cleavage at the C-terminus by SPRTN during normal DNA replication activates the protein kinase activity.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily.|||Chromosome|||Cytoplasm|||Found in all adult tissues tested. Elevated expression in testis, lung and spleen. 15.5 day old embryos show ubiquitous expression with strong expression in brain, liver, kidney, pancreas, intestine, thymus and lung.|||Haploinsufficient for the suppression of genomic instability and tumor progression.|||In the testis, present in cells undergoing meiosis I. Not detected in peripheral cells in seminiferous tubules that are undergoing pre-meiotic DNA synthesis or in late condensing or mature sperm.|||Interacts (phosphorylated by ATR) with RAD51 (By similarity). Interacts with and phosphorylates CLSPN, an adapter protein that regulates the ATR-dependent phosphorylation of CHEK1 (By similarity). Interacts with BRCA1 (By similarity). Interacts with and phosphorylates CDC25A, CDC25B and CDC25C (By similarity). Interacts with FBXO6, which regulates CHEK1 (By similarity). Interacts with PPM1D, which regulates CHEK1 through dephosphorylation (By similarity). Interacts with TIMELESS; DNA damage-dependent (PubMed:23418588). Interacts with FEM1B; activates CHEK1 in response to stress (By similarity). Interacts with TLK1 (By similarity). Interacts with XPO1 and YWHAZ (By similarity). Interacts with CDK5RAP3; antagonizes CHEK1 (By similarity).|||Mice die of apoptosis at the blastocyst stage.|||Nucleus|||Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation. ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity. Phosphorylation at Ser-345 induces a change in the conformation of the protein, activates the kinase activity and is a prerequisite for interaction with FBXO6 and subsequent ubiquitination at Lys-436. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention. Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest. Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination. Also phosphorylated at undefined residues during mitotic arrest, resulting in decreased activity.|||Proteolytically cleaved at the C-terminus by SPRTN during normal DNA replication, thereby promoting CHEK1 removal from chromatin and activating the protein kinase activity.|||Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:10859163, PubMed:10859164, PubMed:15261141). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:10859163, PubMed:10859164, PubMed:15261141). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:10859163, PubMed:10859164, PubMed:15261141). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:10859163, PubMed:10859164, PubMed:15261141). Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA (By similarity). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (PubMed:18243098). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (By similarity). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (By similarity).|||The autoinhibitory region (AIR) inhibits the activity of the kinase domain.|||Ubiquitinated (PubMed:15710331). Mono or diubiquitination promotes nuclear exclusion (PubMed:15710331). The activated form (phosphorylated on Ser-345) is polyubiquitinated at Lys-436 by some SCF-type E3 ubiquitin ligase complex containing FBXO6 promoting its degradation (By similarity). Ubiquitination and degradation are required to terminate the checkpoint and ensure that activated CHEK1 does not accumulate as cells progress through S phase, when replication forks encounter transient impediments during normal DNA replication. 'Lys-63'-mediated ubiquitination by TRAF4 at Lys-132 activates cell cycle arrest and activation of DNA repair (By similarity).|||centrosome http://togogenome.org/gene/10090:Rhpn2 ^@ http://purl.uniprot.org/uniprot/Q8BWR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RHPN family.|||Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity (By similarity).|||Interacts with GTP-bound RhoA and RhoB. Interacts with both GTP- and GDP-bound RhoA. Interacts with KRT18 (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Or13a27 ^@ http://purl.uniprot.org/uniprot/Q8VGL4 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Yipf1 ^@ http://purl.uniprot.org/uniprot/Q91VU1 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the YIP1 family.|||Interacts with YIPF6; this interaction may stabilize YIPF1. May also form a ternary complex with YIPF2 and YIPF6.|||Late endosome membrane|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Als2 ^@ http://purl.uniprot.org/uniprot/Q920R0 ^@ Function|||Subunit ^@ Forms a heteromeric complex with ALS2CL. Interacts with ALS2CL (By similarity).|||May act as a GTPase regulator. Controls survival and growth of spinal motoneurons. http://togogenome.org/gene/10090:Or6k4 ^@ http://purl.uniprot.org/uniprot/E9Q0Q2|||http://purl.uniprot.org/uniprot/Q8VFZ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slitrk3 ^@ http://purl.uniprot.org/uniprot/Q810B9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SLITRK family.|||Broadly expressed in embryonic brain with highest expression in cortical plate, pyramidal cell layer of the hippocampus, thalamus and hypothalamus.|||Membrane|||Suppresses neurite outgrowth. http://togogenome.org/gene/10090:Mapk8ip2 ^@ http://purl.uniprot.org/uniprot/Q548W8|||http://purl.uniprot.org/uniprot/Q6PIT2|||http://purl.uniprot.org/uniprot/Q9ERE9 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JIP scaffold family.|||Cytoplasm|||Forms homo- or heterooligomeric complexes. Binds specific components of the JNK signaling pathway namely JNK1, JNK2, JNK3, MAP2K7, MAP3K10, MAP3K11, MAP3K12 and MAPK13 (By similarity). Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2). Binds the TPR motif-containing C-terminal of kinesin light chain. Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Interacts with DCLK2. Interacts with FGF13; enables the interaction with MAPK13 and may regulate the MAPK8IP2 scaffolding activity. Interacts with TIAM1 and TIAM2 (PubMed:10827199, PubMed:11378392, PubMed:16628014, PubMed:19893486). Interacts with SH3RF2 (By similarity).|||Highly expressed in brain. Expressed in all neurons. Also expressed in testis, primarily in the epididymal epidermis.|||The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. JIP2 inhibits IL1 beta-induced apoptosis in insulin-secreting cells (By similarity).|||Upon neuron differentiation. http://togogenome.org/gene/10090:Zc3h14 ^@ http://purl.uniprot.org/uniprot/Q8BJ05 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZC3H14 family.|||Expressed in hippocampal pyramidal neurons (at protein level) (PubMed:21734151).Expressed in kidney, liver, muscle, heart brain and testes (PubMed:19303045). Expressed in hippocampal pyramidal neurons (PubMed:21734151).|||Interacts with HOOK2. Interacts with ZFC3H1 in a RNase-sensitive manner.|||Involved in poly(A) tail length control in neuronal cells. Binds the polyadenosine RNA oligonucleotides.|||Nucleus speckle http://togogenome.org/gene/10090:Myh7 ^@ http://purl.uniprot.org/uniprot/B2RXX9|||http://purl.uniprot.org/uniprot/Q91Z83 ^@ Caution|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2). Interacts with ECPAS. Interacts (via C-terminus) with LRRC39.|||Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle.|||Represents a conventional myosin. This protein should not be confused with the unconventional myosin-7 (MYO7).|||The cardiac alpha isoform is a 'fast' ATPase myosin, while the beta isoform is a 'slow' ATPase.|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils. Four skip residues (Skip1: Thr-1188, Skip2: Glu-1385, Skip3: Glu-1582 and Skip4: Gly-1807) introduce discontinuities in the coiled-coil heptad repeats. The first three skip residues are structurally comparable and induce a unique local relaxation of the coiled-coil superhelical pitch and the fourth skip residue lies within a highly flexible molecular hinge that is necessary for myosin incorporation in the bare zone of sarcomeres.|||myofibril|||sarcomere http://togogenome.org/gene/10090:Tubb3 ^@ http://purl.uniprot.org/uniprot/Q9ERD7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin family.|||Detected at postnatal day 2 and 4.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with UNC5C (via cytoplasmic domain); this interaction is decreased by NTN1/Netrin-1 (PubMed:28483977). Interacts with NLRP5/MATER at cytoskeleton microtubules (By similarity). Interacts with DPYSL5 (By similarity).|||Expressed in the external granular layer cells of the cerebellar cortex (at protein level).|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||The highly acidic C-terminal region may bind cations such as calcium.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (By similarity). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (By similarity). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (By similarity). TUBB3 plays a critical role in proper axon guidance and maintenance (PubMed:20074521). Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Plays a role in dorsal root ganglion axon projection towards the spinal cord (By similarity).|||cytoskeleton|||filopodium|||growth cone|||lamellipodium http://togogenome.org/gene/10090:Gpsm3 ^@ http://purl.uniprot.org/uniprot/Q3U1Z5 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Cytoplasm|||Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins.|||The GoLoco 1 and/or GoLoco 3 domains exhibit GDI activity towards GDP-bound G(i) alpha protein, but not the GoLoco 2 domain. http://togogenome.org/gene/10090:Spag7 ^@ http://purl.uniprot.org/uniprot/Q7TNE3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Eif2d ^@ http://purl.uniprot.org/uniprot/A0A0R4J298|||http://purl.uniprot.org/uniprot/E9PUG7|||http://purl.uniprot.org/uniprot/Q61211 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the eIF2D family.|||Cytoplasm|||Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits (By similarity).|||Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. http://togogenome.org/gene/10090:C1s2 ^@ http://purl.uniprot.org/uniprot/A0A1W2P7F1|||http://purl.uniprot.org/uniprot/Q8CFG8 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain.|||C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4 (By similarity).|||Inhibited by SERPING1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Specifically expressed in male reproductive tissues.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Slc10a6 ^@ http://purl.uniprot.org/uniprot/Q9CXB2 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Glycosylated.|||Highest expression in lung and testis, moderate expression in heart, bladder and skin, and low expression in blood, liver, stomach, small intestine, spleen, kidney, adrenal gland, seminal vesicle, preputial gland, coagulating gland, lacrimal gland/eye, and brain.|||In humans, 3-beta-sulfooxy-androst-5-en-17-one (DHEAS) is the most abundant circulating steroid sulfate in the human body, it is mainly synthesized from adrenal glands and gonads, whereas rats and mice have low circulating concentrations of DHEAS in the periphery as they can only produce DHEAS in their gonads.|||Knockout mice have normal reproductive phenotype, however, males show higher cholesterol sulfate serum levels than wild-type.|||Membrane|||Transports sulfoconjugated steroid hormones from the extracellular compartment into the cytosol in a sodium-dependent manner without hydrolysis (PubMed:23562556). Steroid sulfate hormones are commonly considered to be biologically inactive metabolites, that may be activated by steroid sulfatases into free steroids (By similarity). May play an important role by delivering sulfoconjugated steroids to specific target cells in reproductive organs (PubMed:23562556). May play a role transporting the estriol precursor 16alpha-hydroxydehydroepiandrosterone 3-sulfate (16a-OH-DHEAS) at the fetal blood vessel endothelium (By similarity). Can also transport other sulfoconjugated molecules such as taurolithocholic acid-3-sulfate and sulfoconjugated pyrenes (By similarity). http://togogenome.org/gene/10090:Atf2 ^@ http://purl.uniprot.org/uniprot/P16951|||http://purl.uniprot.org/uniprot/Q543G2|||http://purl.uniprot.org/uniprot/Q640L6|||http://purl.uniprot.org/uniprot/Q68FE3|||http://purl.uniprot.org/uniprot/Q8CBR9 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to have histone acetyltransferase (HAT) activity, specifically towards histones H2B and H4 in vitro (By similarity). However, it is not clear if this activity is genuine or caused by contamination with other histone acetyltransferases in the assay.|||Belongs to the bZIP family.|||Belongs to the bZIP family. ATF subfamily.|||Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Heterodimerization is essential for its transcriptional activity. Interacts with SMAD3 and SMAD4. Interacts with the HK1/VDAC1 complex. Interacts with NBN, MRE11, XPO1, KAT5 and CUL3 (By similarity). Binds through its N-terminal region to UTF1 which acts as a coactivator of ATF2 transcriptional activity.|||Cytoplasm|||Mitochondrion outer membrane|||Nucleus|||Phosphorylation of Thr-51 by MAPK14 and MAPK11, and at Thr-53 by MAPK1/ERK2, MAPK3/ERK1, MAPK11, MAPK12 and MAPK14 in response to external stimulus like insulin causes increased transcriptional activity. Phosphorylated by PLK3 following hyperosmotic stress. Also phosphorylated and activated by JNK and CaMK4. ATM-mediated phosphorylation at Ser-472 and Ser-480 stimulates its function in DNA damage response. Phosphorylation at Ser-44, Thr-55 and Ser-103 activates its transcriptional activity. Phosphorylation at Thr-51 or Thr-53 enhances acetylation of histones H2B and H4.|||Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro. In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type (By similarity). http://togogenome.org/gene/10090:Mrpl34 ^@ http://purl.uniprot.org/uniprot/Q99N91 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bL34 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Mical1 ^@ http://purl.uniprot.org/uniprot/Q8VDP3 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the SH3 domain of NEDD9. Interacts with VIM and PLXNA3. Interacts with RAB1B, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB1B is of low affinity compared to other Rab proteins; at least in case of RAB8A and RAB10 can bind 2 molecules of the Rab proteins simultaneously (By similarity). Interacts with STK38 and STK38L. Interacts with GRAF1/ARHGAP26, GRAF2/ARHGAP10, RAB8A, RAB8B and RAB10; may bind simultaneously to GRAFs and Rabs and connects GRAFs to Rabs (By similarity). Does not interact with RAB1 and RAB11A (By similarity).|||Belongs to the Mical family.|||Cytoplasm|||Endosome membrane|||Expressed in the postnatal and adult hippocampus; found in dentate gyrus, the polymorphic layer, cornu ammonis (CA) 1-3 and in mossy fibers of the striatum lucidum. In adult hippocampus strongly expressed in CA3 pyramidial neurons.|||Midbody|||Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (By similarity). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels. May act as Rab effector protein and play a role in vesicle trafficking. Promotes endosomal tubule extension by associating with RAB8 (RAB8A or RAB8B), RAB10 and GRAF (GRAF1/ARHGAP26 or GRAF2/ARHGAP10) on the endosomal membrane which may connect GRAFs to Rabs, thereby participating in neosynthesized Rab8-Rab10-Rab11-dependent protein export (By similarity).|||The C-terminal coiled coil part contains the plexin-interacting region.|||The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly Rab8, Rab10, Rab13 and Rab15 (in their GTP-bound forms).|||The reaction mechanism is subject to discussion. Some work suggest MICAL enzymes directly oxidize actin methionine residues to produce methionine-(R)-S-oxide. Other publications suggest that the enzyme functions as a NADPH oxidase producing H(2)O(2) (EC 1.6.3.1) and that it is the produced H(2)O(2) that is responsible for the methionine-(R)-S-oxide production.|||cytoskeleton http://togogenome.org/gene/10090:Msh6 ^@ http://purl.uniprot.org/uniprot/P54276 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA mismatch repair MutS family.|||Chromosome|||Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with MCM9. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains.|||Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction (By similarity).|||Nucleus|||Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.|||The PWWP domain specifically recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3). http://togogenome.org/gene/10090:Gm8765 ^@ http://purl.uniprot.org/uniprot/B7ZWJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Gpr45 ^@ http://purl.uniprot.org/uniprot/Q148B5|||http://purl.uniprot.org/uniprot/Q8CA29|||http://purl.uniprot.org/uniprot/Q9EQQ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Brain specific.|||Cell membrane|||Membrane|||Orphan receptor. May play a role in brain function. http://togogenome.org/gene/10090:Prr7 ^@ http://purl.uniprot.org/uniprot/Q3V0I2 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a synapse-to-nucleus messenger to promote NMDA receptor-mediated excitotoxicity in neurons in a JUN-dependent manner (By similarity). Inhibits ubiquitination-mediated degradation and promotes phosphorylation and transcriptional activity of transcription factor JUN (By similarity). Might play a redundant role in the regulation of T cell receptor signaling (PubMed:27657535). Might promote apoptosis in T cells (By similarity).|||Cell membrane|||Forms a complex with NMDA receptor zeta subunit GRIN1 and epsilon subunit GRIN2B (By similarity). Interacts with GRIN2B (By similarity). Interacts with GRIN1; the interaction is reduced upon NMDA receptor activity (By similarity). Found in a postsynaptic membrane complex with DLG4 and GRIN1 (By similarity). Interacts with DLG4 (via PDZ3 domain and to lesser degree via PDZ2 domain) (By similarity). Interacts with JUN (PubMed:27458189). Found in a complex with JUN and FBXW7 (By similarity). Interacts with JUN and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (By similarity). Interacts with SRC (By similarity).|||Highly expressed in brain, moderately expressed in lymph nodes and T cells and low expression in thymus and spleen. Expressed in single positive progenitor thymocytes, particularly in CD8 single positive thymocytes.|||No visible phenotype. Mice are viable and fertile. T-cell and B-cell development are normal. T cell receptor signaling and activation induced cell death appear normal. Small reduction of CD4 single positive thymocytes.|||Nucleus|||Palmitoylated.|||Postsynaptic cell membrane|||Postsynaptic density membrane|||Synapse|||Tyrosine phosphorylated, possibly by SRC.|||dendrite|||perinuclear region http://togogenome.org/gene/10090:Or7a39 ^@ http://purl.uniprot.org/uniprot/Q7TQU9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grk1 ^@ http://purl.uniprot.org/uniprot/G3X905|||http://purl.uniprot.org/uniprot/Q4V9Z9 ^@ Similarity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily. http://togogenome.org/gene/10090:Bdkrb2 ^@ http://purl.uniprot.org/uniprot/P32299 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family. Bradykinin receptor subfamily. BDKRB2 sub-subfamily.|||Cell membrane|||Forms a complex with PECAM1 and GNAQ. Interacts with PECAM1 (By similarity).|||Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Ecrg4 ^@ http://purl.uniprot.org/uniprot/Q99LS0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||At embryonic stage 14.5 dpc, primarily expressed in the choroid plexus, and low expression in the heart and cartilage (at protein level) (PubMed:21349154). At 18.5 dpc, expressed in adrenal cortex, choroid plexus and bone (PubMed:17284679). Low expression in the brain of young, 2-month-old animals, except for the mitral cell layer of the olfactory bulb (PubMed:20404145). Strongly expressed in the brains of aged, 15- to 21-month-old mice with expression in the subgranular zone of the dentate gyrus and in the corpus callosum (at protein level) (PubMed:20404145). Also expressed in the CA1-3 regions of the hippocampus, as well as in the cerebellum, brainstem and cortex (PubMed:20404145). In vitro, up-regulated in senescent cells, including embryonic fibroblasts and oligodendrocyte precursor cells (PubMed:20404145).|||Belongs to the augurin family.|||Cytoplasm|||Expressed in the intermediate lobe of pituitary, glomerular layer of adrenal cortex, choroid plexus and atrioventricular node of the heart (PubMed:17284679). Expressed in the brain with high expression in the choroid plexus and the epithelial lining of the central canal and expression in the gray matter of the spinal cord (at protein level) (PubMed:21349154).|||Probable hormone that may attenuate cell proliferation and induce senescence of oligodendrocyte and neural precursor cells in the central nervous system (PubMed:20404145). ECRG4-induced senescence is characterized by G1 arrest, RB1 dephosphorylation and accelerated CCND1 and CCND3 proteasomal degradation (PubMed:20404145).|||Secreted http://togogenome.org/gene/10090:Tagln3 ^@ http://purl.uniprot.org/uniprot/Q9R1Q8 ^@ Similarity ^@ Belongs to the calponin family. http://togogenome.org/gene/10090:Tnfrsf11a ^@ http://purl.uniprot.org/uniprot/O35305 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the clefts between the subunits of the TNFSF11 ligand trimer to form a heterohexamer (PubMed:20483727, PubMed:23039992). Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6 (By similarity). Interacts (via cytoplasmic domain) with GAB2 (By similarity). Interacts (via cytoplasmic domain); with EEIG1 (via N-terminus); when in the presence of TNFSF11/RANKL (PubMed:23478294).|||Cell membrane|||Membrane raft|||Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548, PubMed:23478294, PubMed:20483727). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of NFATC1 and activation of PLCG2 (PubMed:23478294). Involved in the regulation of interactions between T-cells and dendritic cells (PubMed:9367155).|||Ubiquitous expression with high levels in trabecular bone, thymus, small intestine, lung, brain and kidney. Weakly expressed in spleen and bone marrow. http://togogenome.org/gene/10090:Vmn1r152 ^@ http://purl.uniprot.org/uniprot/E9Q9N3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tec ^@ http://purl.uniprot.org/uniprot/P24604|||http://purl.uniprot.org/uniprot/Q3TH41|||http://purl.uniprot.org/uniprot/Q3U436|||http://purl.uniprot.org/uniprot/Q8CFK4 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by tyrosine phosphorylation by a wide range of cytokine stimulations. When T-cells or B-cells receptors are activated, a series of phosphorylation leads to the recruitment of TEC to the cell membrane, where it is phosphorylated at Tyr-518. Also activated in response to SCF. Integrin engagement induces tyrosine phosphorylation of TEC in platelets. STAP1 participates in a positive feedback loop by increasing the activity of TEC. SOCS1 is an inhibitor of TEC kinase activity.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Cytoplasm|||Following B-cell or T-cell receptors engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-518. Undergoes also tyrosine phosphorylation during platelet activation.|||Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-82'. May also be involved in the regulation of osteoclast differentiation.|||Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with CD28, FASLG, FGF2, GRB10 and KIT (By similarity). Interacts with VAV1 and JAK2. Interacts with LYN.|||Preferentially expressed in liver. Expression is also seen in the hematopoietic cells such as bone marrow, thymus and spleen. Lower expression is seen in the heart, kidney and ovary.|||The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain.|||The SH3 domain is essential for its targeting to activated CD28 costimulatory molecule.|||cytoskeleton http://togogenome.org/gene/10090:Ces4a ^@ http://purl.uniprot.org/uniprot/Q8R0W5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Probable carboxylesterase.|||Secreted http://togogenome.org/gene/10090:Pkmyt1 ^@ http://purl.uniprot.org/uniprot/Q9ESG9 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development (By similarity).|||Autophosphorylated. Phosphorylated by CDC2-CCNB1 complexes on undefined serine and threonine residues. The phosphorylation by CDC2-CCNB1 complexes may inhibit the catalytic activity (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with CDC2-CCNB1 complex. Can also interact with PIN1 when phosphorylated by CDC2-CCNB1 (By similarity).|||Negatively regulated by hyperphosphorylation during mitosis. The hyperphosphorylated form does not associate with CCNB1-CDC2 complexes. The PLK1 protein kinase may be required for mitotic phosphorylation (By similarity).|||The membrane-association motif is essential for the localization to membrane of Golgi stack. According to some authors, it is a transmembrane domain; the existence of a transmembrane region of such is however unsure (By similarity). http://togogenome.org/gene/10090:Tspan5 ^@ http://purl.uniprot.org/uniprot/D3Z641|||http://purl.uniprot.org/uniprot/P62080 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Interacts with ADAM10.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Regulates ADAM10 maturation and trafficking to the cell surface (PubMed:23035126). Promotes ADAM10-mediated cleavage of CD44 (By similarity). http://togogenome.org/gene/10090:Gm20906 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Olfr1141 ^@ http://purl.uniprot.org/uniprot/Q8VFQ7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Taar7a ^@ http://purl.uniprot.org/uniprot/Q5QD12 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Prrc2c ^@ http://purl.uniprot.org/uniprot/Q3TLH4 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Contaminating sequence. Potential poly-A sequence.|||Probable cloning artifact.|||Required for efficient formation of stress granules.|||Stress granule http://togogenome.org/gene/10090:Vmn1r33 ^@ http://purl.uniprot.org/uniprot/Q8R2E0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r84 ^@ http://purl.uniprot.org/uniprot/Q8R284 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ubqln2 ^@ http://purl.uniprot.org/uniprot/Q9QZM0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Degraded during macroautophagy.|||Dimerization is dependent upon the central region of the protein containing the STI1 domains and is independent of its ubiquitin-like and UBA domains.|||Highly expressed in smooth muscle. Expression in other tissues is very low.|||Homodimer. Forms heterodimer with UBQLN1. Binds UBE3A and BTRC. Interacts with the 19S proteasome subunit. Interacts with C9orf72 (By similarity). Binds CD47 (PubMed:10549293). Interacts with HNRNPA1 and HNRNPU. Found in a complex with UBQLN1 and MAP1LC3A/B/C. Interacts with EPS15, EPN1 and EPN2. Interacts with HERPUD1. Interacts with RAD23A. Interacts with TARDBP. Interacts (via C-terminus) with FAF2 (via N-terminus). Interacts with UBQLN4 (By similarity).|||Membrane|||Nucleus|||Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome. Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome. Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion. Negatively regulates the endocytosis of GPCR receptors: AVPR2 and ADRB2, by specifically reducing the rate at which receptor-arrestin complexes concentrate in clathrin-coated pits (CCPs) (By similarity). Links CD47 to vimentin-containing intermediate filaments of the cytoskeleton (PubMed:10549293).|||The UBA domain is essential for its association with microtubule-associated protein 1 light chain 3 (MAP1LC3). Mediates its association with ubiquitinated substrates.|||The ubiquitin-like domain is essential for its inhibitory effect on GPCR endocytosis. Mediates its association with the subunits of the proteasome.|||autophagosome http://togogenome.org/gene/10090:Rimklb ^@ http://purl.uniprot.org/uniprot/Q80WS1 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RimK family.|||Binds 2 magnesium or manganese ions per subunit.|||Catalyzes the synthesis of beta-citryl-L-glutamate and N-acetyl-L-aspartyl-L-glutamate. Beta-citryl-L-glutamate is synthesized more efficiently than N-acetyl-L-aspartyl-L-glutamate.|||Cytoplasm|||N-acetyl-L-aspartyl-L-glutamate (NAAG) is the most abundant dipeptide present in vertebrate central nervous system (CNS). Beta-citryl-L-glutamate, a structural analog of NAAG, is present in testis and immature brain.|||Strongly expressed in brain and testis. Expressed in eyes, thymus, lung, kidney, skeletal muscle, spleen, skin and heart. Expressed in neurons of the neocortex, the gray matter and Purkinje cells. http://togogenome.org/gene/10090:Bod1l ^@ http://purl.uniprot.org/uniprot/E9Q6J5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BOD1 family.|||Chromosome|||Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM. Does not regulate spindle orientation.|||Interacts (via COMPASS-Shg1 domain) with SETD1A at stalled replication forks; this interaction mediates FANCD2-dependent nucleosome remodeling at reversed forks protecting them from nucleolytic degradation. http://togogenome.org/gene/10090:Csnka2ip ^@ http://purl.uniprot.org/uniprot/Q8CH19 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed exclusively in testis (at protein level). Within testis, expressed mainly in the intermediate compartment of the seminiferous tubules with weaker expression in the basal and adluminal compartments.|||Interacts (via C-terminus) with CSNK2A2.|||May play a role in chromatin regulation of male germ cells.|||Nucleus|||Phosphorylated by CK2 (casein kinase II), specifically by complexes containing catalytic subunit CSNK2A2. http://togogenome.org/gene/10090:Or8b12i ^@ http://purl.uniprot.org/uniprot/Q8VGG4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sbno2 ^@ http://purl.uniprot.org/uniprot/Q7TNB8 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional coregulator, that can have both coactivator and corepressor functions (PubMed:18025162, PubMed:23980096). Inhibits the DCSTAMP-repressive activity of TAL1, hence enhancing the access of the transcription factor MITF to the DC-STAMP promoter in osteoclast (PubMed:23980096). Plays a role in bone homeostasis; required as a positive regulator in TNFSF11//RANKL-mediated osteoclast fusion via a DCSTAMP-dependent pathway (PubMed:23980096). May also be required in the regulation of osteoblast differentiation (PubMed:23980096). Involved in the transcriptional corepression of NF-kappaB in macrophages. Plays a role as a regulator in the pro-inflammatory cascade (By similarity).|||Belongs to the SBNO family.|||Expressed in the spleen and bone marrow, and to a lesser extent in the kidney, liver, brain, skin, heart and muscle (PubMed:23980096). Expressed predominantly in osteoclasts, and to a lesser extent in T-cells, B-cells and osteoblasts (PubMed:23980096). Expressed in macrophages (PubMed:18025162).|||Interacts with TAL1; this interaction inhibits TAL1 occupancy of the DCSTAMP promoter, leading to the activation of the DCSTAMP promoter by the transcription factor MITF (PubMed:23980096).|||Mice display a severe osteopetrotic phenotype characterized with an increased bone mass (PubMed:23980096). Show a reduction in the osteoclast surface/bone surface and eroded surface/bone surface ratio, but the osteoclast number/bone surface ratio is normal (PubMed:23980096). Show also a reduction in nuclei/osteoclast ratio (PubMed:23980096). Exhibit an impairment in TNFSF11//RANKL-mediated osteoclast fusion (PubMed:23980096). Show a slight inhibition of osteoblast differentiation (PubMed:23980096).|||Up-regulated by interleukin IL6 together with soluble interleukin receptor IL6R in astrocytes (PubMed:25903009). Up-regulated by interleukins such as IL1B or tumor necrosis factor TNF in astrocytes (at protein level) (PubMed:25903009). Up-regulated by interleukin IL6 together with soluble interleukin receptor IL6R in astrocytes (PubMed:25903009). Up-regulated also by other cytokines such as interleukin IL11, oncostatin M (OSM) and leukemia inhibitory factor (LIF) (PubMed:25903009). Up-regulated by interleukin such as IL1B or tumor necrosis factor TNF in astrocytes (PubMed:25903009). Up-regulated by lipopolysaccharide (LPS) (PubMed:25903009, PubMed:23980096). Up-regulated by interleukin IL10 in a STAT3-dependent manner in bone marrow derived macrophages (PubMed:18025162). Up-regulated by TNFSF11//RANKL in a c-Fos/FOS-dependent manner (PubMed:23980096). http://togogenome.org/gene/10090:Fbxo39 ^@ http://purl.uniprot.org/uniprot/Q5NBU5 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Bex2 ^@ http://purl.uniprot.org/uniprot/Q9WTZ8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BEX family.|||Cytoplasm|||Interacts with LMO2, possibly leading to regulate the transcriptional activity of a DNA-binding complex containing LMO2 (By similarity). Interacts with OMP (PubMed:12911636, PubMed:15198671).|||Nucleus|||Primarily localized to neuronal cells within several regions of the brain, including the olfactory epithelium, bulb, peri/paraventricular nuclei, suprachiasmatic nucleus, arcuate nucleus, median eminence, lateral hypothalamic area, thalamus, hippocampus and cerebellum (at protein level).|||Regulator of mitochondrial apoptosis and G1 cell cycle (By similarity). Regulates the level of PP2A regulatory subunit B and PP2A phosphatase activity (By similarity). In absence of reductive stress, acts as a pseudosubstrate for the CRL2(FEM1B) complex: associates with FEM1B via zinc, thereby preventing association between FEM1B and its substrates (PubMed:34562363).|||The histidine cluster (His cluster) and Cys-126 mediate zinc-binding. http://togogenome.org/gene/10090:Tas2r105 ^@ http://purl.uniprot.org/uniprot/Q53Z46|||http://purl.uniprot.org/uniprot/Q9JKT4 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in gastric and duodenal tissues.|||Gustducin-coupled cycloheximide receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.|||Membrane|||Mice fail to avoid cycloheximide at low concentrations and show a lack of cycloheximide-induced action potentials in a principal nerve innervating taste receptor cells of the tongue.|||Several bitter taste receptors are expressed in a single taste receptor cell.|||Variations in Tas2r105 are associated with avoidance of cycloheximide at low concentrations. http://togogenome.org/gene/10090:Sox17 ^@ http://purl.uniprot.org/uniprot/Q61473 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as transcription regulator that binds target promoter DNA and bends the DNA (PubMed:8636240, PubMed:24153254, PubMed:19328208). Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3' (PubMed:8636240). Modulates transcriptional regulation via WNT3A. Inhibits Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key role in the regulation of embryonic development (PubMed:11973269, PubMed:17655922, PubMed:24153254). Required for normal development of the definitive gut endoderm (PubMed:11973269). Required for normal looping of the embryonic heart tube. Plays an important role in embryonic and postnatal vascular development, including development of arteries (PubMed:24153254). Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX18 (PubMed:16895970). Required for the generation and maintenance of fetal hematopoietic stem cells, and for fetal hematopoiesis (PubMed:17655922). Probable transcriptional activator in the premeiotic germ cells.|||Detected in lung and testis (PubMed:8636240). Detected in endothelial cells around small and large arteries in newborns and adults, but is barely detectable in veins (at protein level) (PubMed:24153254). Detected in lung and testis (PubMed:8636240).|||Detected in the extraembryonic region of the visceral endoderm of pre-streak and early-streak embryos. Detected in the extraembryonic region of the visceral endoderm and in the definitive endoderm at 7.5 dpc. By the seven to eight somite stage, detected in the posterior endoderm, mainly in the endoderm of the midgut and hindgut invagination. Expressed in spermatogonia. The expression clearly declines from the early pachytene spermatocyte stage onward. In contrast, expression of isoform 2 (T-SOX17) begins at the pachytene spermatocyte stage and is highly accumulated in round spermatids (PubMed:11973269). Detected in arterial endothelium in embryos and yolk sac at 10.5 dpc (PubMed:24153254).|||Embryonic lethal due to defects in the development of the definite gut endoderm, aberrant heart looping and severe defects in vascular development and remodeling, including a lack of artery formation. Embryos die at about 10.5 dpc (PubMed:11973269, PubMed:17655922, PubMed:24153254). Besides, mutant embryos display a severe defect in fetal hematopoiesis (PubMed:17655922).|||Has no DNA-binding activity, and does not function as transcriptional activator.|||Interacts with CTNNB1, LEF1 and TCF4.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Zscan25 ^@ http://purl.uniprot.org/uniprot/B2RX31 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ctnnal1 ^@ http://purl.uniprot.org/uniprot/O88327 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the vinculin/alpha-catenin family.|||Cell membrane|||Interacts with ARHGEF1.|||May modulate the Rho pathway signaling by providing a scaffold for the Lbc Rho guanine nucleotide exchange factor (ARHGEF1).|||cytoskeleton http://togogenome.org/gene/10090:Il36b ^@ http://purl.uniprot.org/uniprot/Q08EA6|||http://purl.uniprot.org/uniprot/Q9D6Z6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-1 family.|||Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Stimulates production of interleukin-6 and interleukin-8 in synovial fibrobasts, articular chondrocytes and mature adipocytes. Induces expression of a number of antimicrobial peptides including beta-defensin 4 and beta-defensin 103 as well as a number of matrix metalloproteases (By similarity). Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. Induces the production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs), including IL-12, Il-1 beta, IL-6, TNF-alpha and IL-23, and activates p38 MAPK phosphorylation in BMDCs. Involved in dendritic cell maturation by stimulating the surface expression of CD80, CD86 and MHC class II. Induces the production of IFN-gamma, IL-4 and IL-17 by T-helper 1 (Th1) cells, cultured CD4(+) T-cells and splenocytes.|||Cytoplasm|||Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||N-terminal truncation leads to a dramatic enhancement of its activity (>1000-fold).|||Secreted http://togogenome.org/gene/10090:Fthl17f ^@ http://purl.uniprot.org/uniprot/Q3SXD2 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Ovol3 ^@ http://purl.uniprot.org/uniprot/D3YYM0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May act as a transcription regulator.|||Nucleus http://togogenome.org/gene/10090:Ddx31 ^@ http://purl.uniprot.org/uniprot/Q6NZQ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DDX31/DBP7 subfamily.|||Interacts with NPM1; the interaction prevents interaction between NPM1 and HDM2.|||Probable ATP-dependent RNA helicase (By similarity). Plays a role in ribosome biogenesis and TP53/p53 regulation through its interaction with NPM1 (By similarity).|||nucleolus http://togogenome.org/gene/10090:Tmem132a ^@ http://purl.uniprot.org/uniprot/Q922P8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM132 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with HSPA5/GRP78.|||May play a role in embryonic and postnatal development of the brain. Increased resistance to cell death induced by serum starvation in cultured cells. Regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation (By similarity). http://togogenome.org/gene/10090:Erlin2 ^@ http://purl.uniprot.org/uniprot/Q8BFZ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the band 7/mec-2 family.|||Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs) such as ITPR1. Promotes sterol-accelerated ERAD of HMGCR probably implicating an AMFR/gp78-containing ubiquitin ligase complex. Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. May promote ER retention of the SCAP-SREBF complex (By similarity).|||Endoplasmic reticulum membrane|||Forms a heteromeric complex with ERLIN1 (By similarity). In complex with ERLIN1, interacts with RNF170 (PubMed:21610068). Interacts with activated ITPR1, independently of the degree of ITPR1 polyubiquitination (PubMed:17502376). Interacts with SCAP, INSIG1, SREBF1 and SREBF2 under cholesterol sufficiency conditions; indicative for an association with the SCAP-SREBP-INSIG complex (By similarity). Probably part of an AMFR/gp78 and INSIG1-containing ubiquitin ligase complex involved in ERAD of HMGCR (By similarity). Interacts with TMUB1; TMUB1 bridges the association with AMFR (By similarity). Interacts with SYVN1 and RNF139 (By similarity). Interacts with TMEM259 (PubMed:25977983). Interacts with TMEM41B (By similarity). http://togogenome.org/gene/10090:Rag1 ^@ http://purl.uniprot.org/uniprot/P15919 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated in the presence of CDC34/UBCH3.|||Belongs to the RAG1 family.|||Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).|||Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1.|||Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Interacts with DCAF1, leading to recruitment of the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone repair during V(D)J recombination.|||Maturing lymphoid cells and central nervous system.|||Mice display a severe combined immunodeficiency phenotype. The have a small lymphoid organs that do not contain mature B and T-lymphocytes. The arrest of B- and T-cell differentiation occurs at an early stage and correlates with the inability to perform V(D)J recombination. The frequency of homologous immunoglobulin pairing is much lower. No obvious neuroanatomical or behavioral abnormalities have been observed.|||Nucleus|||The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp.|||The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity. http://togogenome.org/gene/10090:Slc10a2 ^@ http://purl.uniprot.org/uniprot/P70172|||http://purl.uniprot.org/uniprot/Q0VBB8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Expressed in ileum.|||Membrane|||Monomer and homodimer.|||Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:10101301). Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate (PubMed:10101301). Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids. Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (By similarity). http://togogenome.org/gene/10090:Marchf3 ^@ http://purl.uniprot.org/uniprot/Q8BRX9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle membrane|||E3 ubiquitin-protein ligase which may be involved in endosomal trafficking. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.|||Early endosome membrane|||Interacts with MARCHF2 and STX6.|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Mfrp ^@ http://purl.uniprot.org/uniprot/Q8K480 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Defects in Mfrp are the cause of retinal degeneration 6 (RD6). RD6 is an autosomal recessive degeneration of the photoreceptors causing dysfunction of both rods and cones.|||Expressed in retinal pigment epithelium and ciliary epithelium of the eye.|||Interacts with C1QTNF5.|||May play a role in eye development. http://togogenome.org/gene/10090:Ankrd23 ^@ http://purl.uniprot.org/uniprot/Q812A3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with titin/TTN and MYPN.|||May be involved in the energy metabolism. Could be a molecular link between myofibrillar stretch-induced signaling pathways and muscle gene expression.|||Nucleus http://togogenome.org/gene/10090:Ska1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0M5|||http://purl.uniprot.org/uniprot/Q9CPV1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKA1 family.|||Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules. In the complex, it mediates the interaction with microtubules.|||Component of the SKA1 complex, composed of SKA1, SKA2 and SKA3. Forms a heterodimer with SKA2; the heterodimer interacting with SKA3. The core SKA1 complex is composed of 2 SKA1-SKA2 heterodimers, each heterodimer interacting with a molecule of the SKA3 homodimer. The core SKA1 complex associates with microtubules and forms oligomeric assemblies. Interacts with microtubules; the interaction is direct. Interacts with SKA2. Interacts with SKA3.|||kinetochore|||spindle http://togogenome.org/gene/10090:Nelfcd ^@ http://purl.uniprot.org/uniprot/Q922L6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NELF-D family.|||Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (By similarity). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (By similarity).|||Nucleus|||The NELF complex is composed of NELFA, NELFB, NELFCD and NELFE; NELFA and NELFCD form a stable subcomplex that binds primarily through NELFCD to the N-terminus of NELFB (By similarity). Binds RNA which may help to stabilize the NELF complex on nucleic acid (By similarity). In vitro, the NELFA:NELFCD subcomplex binds to ssDNA and ssRNA in a sequence- and structure-dependent manner (By similarity). Interacts with ARAF1 (By similarity). Interacts with PCF11 (By similarity). Interacts with NELFB (PubMed:26010750). Interacts with KAT8 (PubMed:17335777). http://togogenome.org/gene/10090:Ube2d1 ^@ http://purl.uniprot.org/uniprot/P61080|||http://purl.uniprot.org/uniprot/Q3UFQ4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1. Ubiquitinates STUB1-associated HSP90AB1 in vitro. Lacks inherent specificity for any particular lysine residue of ubiquitin. Essential for viral activation of IRF3. Mediates polyubiquitination of CYP3A4.|||Autoubiquitinated.|||Belongs to the ubiquitin-conjugating enzyme family.|||Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with RNF11.|||Cytoplasm http://togogenome.org/gene/10090:Fam221a ^@ http://purl.uniprot.org/uniprot/Q8C790 ^@ Similarity ^@ Belongs to the FAM221 family. http://togogenome.org/gene/10090:Smad5 ^@ http://purl.uniprot.org/uniprot/P97454 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dwarfin/SMAD family.|||Cytoplasm|||Disruption of SMAD5 gene leads to the mid-gestation death of mutant embryos largely due to extraembryonic yolk sac defects.|||Homodimer. Forms trimers with the co-SMAD SMAD4 (By similarity). Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1. Interacts with TMEM119 (PubMed:21239498). Interacts with ZNF8 (PubMed:12370310). Interacts with RANBP3L (By similarity). Interacts with HK1 (By similarity). Interacts with HGS; this interaction attenuates BMP signaling (By similarity).|||Mitochondrion|||Nucleus|||Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.|||Predominantly expressed in mesenchyme and somites during embryogenesis, and present in many tissues of the adult.|||Transcriptional regulator that plays a role in various cellular processes including embryonic development, cell differentiation, angiogenesis and tissue homeostasis (PubMed:10079220, PubMed:12393578). Upon BMP ligand binding to their receptors at the cell surface, is phosphorylated by activated type I BMP receptors (BMPRIs) and associates with SMAD4 to form an heteromeric complex which translocates into the nucleus acting as transcription factor. In turn, the hetero-trimeric complex recognizes cis-regulatory elements containing Smad Binding Elements (SBEs) to modulate the outcome of the signaling network (PubMed:26304548). Non-phosphorylated SMAD5 has a cytoplasmic role in energy metabolism regulation by promoting mitochondrial respiration and glycolysis in response to cytoplasmic pH changes. Mechanistically, interacts with hexokinase 1/HK1 and thereby accelerates glycolysis.|||Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1. http://togogenome.org/gene/10090:Dgkz ^@ http://purl.uniprot.org/uniprot/A0A668KL90|||http://purl.uniprot.org/uniprot/A2AHJ7|||http://purl.uniprot.org/uniprot/A2AHK0|||http://purl.uniprot.org/uniprot/Q80UP3 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Cell membrane|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:12883552). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:12883552). Also plays an important role in the biosynthesis of complex lipids (Probable). Does not exhibit an acyl chain-dependent substrate specificity among diacylglycerol species. Can also phosphorylate 1-alkyl-2-acylglycerol in vitro but less efficiently and with a preference for alkylacylglycerols containing an arachidonoyl group (By similarity). The biological processes it is involved in include T cell activation since it negatively regulates T-cell receptor signaling which is in part mediated by diacylglycerol (PubMed:12883552). By generating phosphatidic acid, stimulates PIP5KIA activity which regulates actin polymerization (By similarity). Through the same mechanism could also positively regulate insulin-induced translocation of SLC2A4 to the cell membrane (PubMed:27739494). Regulates RASGRP1 activity (By similarity).|||Homozygous knockout mice are viable, fertile and do not display overt phenotype (PubMed:12883552). Slight perturbations of the cellular composition of secondary lymphoid organs with a slight decrease of mature T cells is observed (PubMed:12883552). Upon TCR activation the normal conversion of diacylglycerol into phosphatidic acid that negatively regulates TCR signaling is partially impaired (PubMed:12883552). Hyper proliferation of T-cells and the ability to mount a more vigorous and effective T-cell response against pathogens indicate a more profound T-cell activation in these mice (PubMed:12883552).|||Interacts (via PDZ-binding motif) with the PDZ domain of the syntrophin SNTG1 and that of SNX27 (By similarity). Interacts with IRS1 in the absence of insulin; insulin stimulation decreases this interaction (PubMed:27739494). Found in a ternary complex with IRS1 and PIP5K1A in the absence of insulin (PubMed:27739494). Interacts with PIP5K1A (By similarity). Forms a signaling complex with RASGRP1 and HRAS (By similarity).|||Nucleus|||The PDZ-binding motif mediates interaction with PDZ domain-containing proteins like SNTG1 and SNX27.|||cytosol|||lamellipodium http://togogenome.org/gene/10090:Prr12 ^@ http://purl.uniprot.org/uniprot/E9PYL2 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in brain.|||Nucleus|||Postsynaptic density|||Strongest expression found in embryonic day 15 dpc compared to postnatal day P1 and adult brain.|||synaptosome http://togogenome.org/gene/10090:Rtp1 ^@ http://purl.uniprot.org/uniprot/Q8C8C1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM7 family.|||Cell membrane|||Interacts with olfactory receptors.|||Predominantly expressed in olfactory and vomeronasal organs, in mature olfactory sensory neurons.|||Specifically promotes functional cell surface expression of olfactory receptors, but not of other GPCRs. http://togogenome.org/gene/10090:Ptpn11 ^@ http://purl.uniprot.org/uniprot/P35235 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus (PubMed:14967142). Positively regulates MAPK signal transduction pathway (By similarity). Dephosphorylates GAB1, ARHGAP35 and EGFR (By similarity). Dephosphorylates ROCK2 at 'Tyr-722' resulting in stimulation of its RhoA binding activity (By similarity). Dephosphorylates CDC73 (By similarity). Dephosphorylates SOX9 on tyrosine residues, leading to inactivate SOX9 and promote ossification (PubMed:29644115). Dephosphorylates tyrosine-phosphorylated NEDD9/CAS-L (By similarity).|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.|||Conditional deletion in limb and head mesenchyme leads to increased cartilage mass and deficient ossification: osteochondroprogenitors become chondrocytes and not osteoblasts caused by inability of PTPN11/SHP2 to mediate tyrosine dephosphorylation of SOX9.|||Cytoplasm|||Highly expressed in brain, heart and kidney.|||Interacts with CD84 and with phosphorylated SIT1 and MZPL1. Interacts with FCRL4, FCRL6 and ANKHD1. Interacts with GAREM1 (tyrosine phosphorylated); the interaction increases MAPK/ERK activity and does not affect the GRB2/SOS complex formation (By similarity). Interacts with PTPNS1 and BCAR3. Interacts with phosphorylated LIME1. Interacts with SHB and INPP5D/SHIP1. Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). Interacts with GAB2. Interacts with TERT; the interaction retains TERT in the nucleus. Interacts with PECAM1 and FER. Interacts with EPHA2 (activated); participates in PTK2/FAK1 dephosphorylation in EPHA2 downstream signaling (By similarity). Interacts with MILR1 (tyrosine phosphorylated). Interacts with FLT1 (tyrosine-phosphorylated), FLT3 (tyrosine-phosphorylated), FLT4 (tyrosine-phosphorylated), KIT and GRB2. Interacts with ROS1; mediates PTPN11 phosphorylation. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with PDGFRB (tyrosine phosphorylated); this interaction increases the PTPN11 phosphatase activity. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with SIGLEC10 (PubMed:23374343). Interacts with Lilrb4a (when tyrosine phosphorylated) (PubMed:10026201). Interacts with SIGLEC10 (By similarity). Interacts with CLEC12B (via ITIM motif); this interaction triggers dephosphorylation and activation of PTPN11. Interacts (via SH2 domains) with NEDD9/CAS-L; the interaction is enhanced when NEDD9/CAS-L is tyrosine phosphorylated (By similarity).|||Phosphorylated on Tyr-542 and Tyr-580 upon receptor protein tyrosine kinase activation; which creates a binding site for GRB2 and other SH2-containing proteins. Phosphorylated upon activation of the receptor-type kinase FLT3. Phosphorylated by activated PDGFRB (By similarity). Phosphorylated upon activation of the receptor-type kinase PDGFRA.|||The SH2 domains repress phosphatase activity. Binding of these domains to phosphotyrosine-containing proteins relieves this auto-inhibition, possibly by inducing a conformational change in the enzyme. http://togogenome.org/gene/10090:Or2y1 ^@ http://purl.uniprot.org/uniprot/Q7TQT1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Map3k3 ^@ http://purl.uniprot.org/uniprot/Q61084 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Activated by phosphorylation on Thr-530.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2. Interacts with MAP2K5 and SPAG9.|||Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.|||Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its activity. http://togogenome.org/gene/10090:Plekhb1 ^@ http://purl.uniprot.org/uniprot/Q9QYE9 ^@ Disruption Phenotype|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds transducins (By similarity). Homodimer. Interacts (via PH domain) with MYO1C. Interacts (via PH domain) with MYO7A.|||Cytoplasm|||Highly expressed in retina and brain. In retina, abundantly expressed in photoreceptors. Isoform 4 is the predominant isoform expressed in mature olfactory receptor neurons and vestibular and cochlear hair cells. Also expressed in cells with possible sensory function, including peripheral retinal ganglion cells, cochlear interdental cells, and neurons of the circumventricular organ (at protein level).|||Membrane|||Mice appear normal at birth with no obvious behavioral or growth abnormalities nor overt sensory deficits. At 6 months and 1 year of age, mice display normal retinal histology and normal response in electroretinograms. http://togogenome.org/gene/10090:Srpk2 ^@ http://purl.uniprot.org/uniprot/O54781 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Ser-50 and Ser-581.|||Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs) (By similarity). Interacts with PKB/AKT1 in a phosphorylation-dependent manner (By similarity). The phosphorylated form (by PKB/AKT1) interacts with YWHAB and YWHAE (By similarity). Interaction with YWHAB suppresses its cleavage by caspases and inhibits the release of its N-terminal pro-apoptotic fragment (By similarity). Interacts with SFN (By similarity). Interacts with ACIN1 (PubMed:18559500). Interacts with POLR2A/RNA polymerase II; the interaction occurs during the co-transcriptional formation of inappropriate R-loops (By similarity).|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.|||Chromosome|||Cytoplasm|||Expressed in testes, lung and brain.|||Nucleus speckle|||Phosphorylation at Thr-485 by PKB/AKT1 enhances its stimulatory activity in triggering cyclin-D1 (CCND1) expression and promoting apoptosis in neurons, which can be blocked by YWHAB. It also enhances its protein kinase activity toward ACIN1 and SRSF2, promotes its nuclear translocation and prevents its proteolytic cleavage (By similarity).|||Proteolytically cleaved at Asp-137 and Asp-401 by caspase-3 during apoptotic cell death. Cleavage at Asp-137 which is the major site of cleavage, produces a small N-terminal fragment that translocates into nucleus and promotes VP16-induced apoptosis (By similarity).|||Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing (PubMed:9446799). Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression (PubMed:19592491). This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression (By similarity). Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation (By similarity). Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28 (By similarity). Probably by phosphorylating DDX23, leads to the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:C3 ^@ http://purl.uniprot.org/uniprot/P01027 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a chemoattractant for neutrophils in chronic inflammation.|||Adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2.|||C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.|||C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha, linked by a disulfide bond. C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin and generating C3b (beta chain + alpha' chain). Forms the pro-C3-convertase enzyme complex by interacting with Complement factor B Bb fragment (Bb), which is then stabilized by binding CFP, allowing the complex to become active (By similarity). The interaction with Bb is dependent on Mg2+ (By similarity). C3b interacts with CR1 (via Sushi 8 and Sushi 9 domains). C3b interacts with CFH. C3d interacts with CFH. C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and 2). During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with VSIG4. Interacts with S.aureus immunoglobulin-binding protein sbi, this prevents interaction between C3dg and CR2. Interacts with S.aureus fib. Interacts (both C3a and ASP) with C5AR2; the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of C5AR2, recruitment of ARRB2 to the cell surface and endocytosis of GRP77.|||C3b is rapidly split in two positions by factor I and a cofactor to form iC3b (inactivated C3b) and C3f which is released. Then iC3b is slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha' chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. Other proteases produce other fragments such as C3d or C3g. C3a is further processed by carboxypeptidases to release the C-terminal arginine residue generating the acylation stimulating protein (ASP). Levels of ASP are increased in adipocytes in the postprandial period and by dietary chylomicrons.|||Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity). It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. The short isoform has B-cell stimulatory activity.|||Null mice displayed altered lipid metabolism and morphological changes in adipocyte distribution. There is reduced adipsin/CFD expression, increased number of smaller fat cells, decreased DGAT1 expression and activity, and less triglyceride storage capacity associated with delayed postprandial clearance. Mice on a high-fat diet exihibited no diet-induced up-regulation of adipsin/CFD expression nor adipocyte differentiation.|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Dtnbp1 ^@ http://purl.uniprot.org/uniprot/Q91WZ8 ^@ Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dysbindin family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Defects in Dtnbp1 are the cause of the sandy (sdy) mutant phenotype, a model for human Hermansky-Pudlak syndrome (HPS). Sdy mice lack dysbindin expression; they have a characteristic sandy coat color and have much fewer melanosomes in the retinal pigment epithelium and choroid. They are fully viable, but present behavioral abnormalities. They have prolonged bleeding times due to platelet storage pool deficiency, and lysosomal storage defects. The number of electron-opaque platelet dense granules is severely reduced, and the platelet serotonin content is strongly reduced. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy mice also display impaired long-term memory retention and working memory and schizophrenia-like behavioral abnormalities. Vesicle morphology and kinetics of transmitter release are affected in both neuroendocrine cells and hippocampal synapses, characterized by larger vesicle size, slower quantal release, fewer release events and reduced readily releasable pool (RRP). Expression levels of SYN1 are lower in both the cortex and the hippocampal formation (HF).|||Detected in brain, in hippocampus and dentate gyrus neurons. Detected at axon bundles and axon terminals, notably in the cerebellum and hippocampus. Detected in neuropil in hippocampus, lateral septum, basal ganglia and substantia nigra. Highly expressed in pyramidal cells of hippocampus CA2 and CA3. Detected at the heart and skeletal muscle sarcolemma (at protein level). Ubiquitously expressed. The highest expression is observed in testis, liver, kidney, brain, heart and lung. Expressed at lower levels in stomach and small intestine.|||Endoplasmic reticulum|||Endosome membrane|||Interacts with AP3M1 and TRIM32. Interacts (isoform 1 and isoform 2 only) with the DNA-dependent protein kinase complex DNA-PK; the interaction phosphorylates DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and XRCC6. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. This BLOC-1 complex also associates with the BLOC-2 complex in endosomes. Binds to DTNA and DTNB but may not be a physiological binding partner (PubMed:16448387, PubMed:16980328). Interacts (via its coiled coil domain) with KXD1. Interacts with AP3B2, BLOC1S5, BLOC1S6, CMYA5, PI4K2, RNF151 and SNAPIN/BLOC1S8. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus.|||Melanosome membrane|||Nucleus|||Null mice exhibit cognitive abnormalities including schizophrenia-related behaviors such as impaired working memory under stressful conditions. There is higher acoustic startle reactivity to stimuli. Pyramidal neurons are hypoexcitable on dopamine-2 receptor stimulation. There is reduced expression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and CaMKKbeta in the medial prefrontal cortex mPFC. There is increased expression levels of cell surface dopamine receptor D2 in cortical neurons. Expression levels of SYN1 are lower in both cortex and in the hippocampal formation (HF).|||Postsynaptic cell membrane|||Postsynaptic density|||Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1 degradation.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Erfe ^@ http://purl.uniprot.org/uniprot/Q6PGN1 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adipolin/erythroferrone family.|||Expressed in the soleus muscle in the leg (at protein level) (PubMed:22351773, PubMed:30566056). Found in blood (at protein level) (PubMed:22351773, PubMed:24187137). Weakly expressed in the heart (at protein level) (PubMed:22351773, PubMed:30566056). Predominantly expressed in skeletal muscle and, at much lower levels, in other tissues, including lung, eye, smooth muscle, brain and kidney (PubMed:22351773, PubMed:24187137). Within skeletal muscles, higher expression levels in soleus as compared with plantaris (PubMed:22351773). Expressed in osteoblasts, mature osteoclasts and erythroblasts (PubMed:34002695). When fasting, females tend to have higher circulating levels than males (PubMed:22351773). Obese mice tend to have lower expression and circulating levels as compared to lean animals (PubMed:22351773). Following EPO treatment, only expressed in bone marrow and spleen (PubMed:24880340).|||Homodimer; disulfide-linked (PubMed:22351773). Forms trimer, hexamers and higher molecular weight oligomers (PubMed:32602701). May form heteromeric complexes with C1QTNF2 and C1QTNF12 and, to a lesser extent, with C1QTNF5 and C1QTNF10 (PubMed:22351773). Interacts with BMP5 and BMP7; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509). Interacts with BMP6; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509, PubMed:31800957). Interacts with BMP2 (PubMed:31800957). Interacts with heterodimers composed of BMP2 and BMP6 in vitro, the interaction inhibits the heterodimer binding to its receptor BMPR1A /ALK3 and thereby suppresses expression of HAMP (PubMed:31800957).|||Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage: produced by erythroblasts following blood loss and mediates suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores (PubMed:24880340, PubMed:30097509, PubMed:31800957, PubMed:34002695). Promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake (PubMed:22351773). Inhibits apoptosis and inflammatory response in cardiomyocytes via promotion of sphingosine-1-phosphate (S1P) and cAMP-dependent activation of AKT signaling (PubMed:30566056). Inhibits autophagy induced by nutrient deficiency in hepatocytes via promoting the phosphorylation of IRS1, AKT, and MTOR, and thereby subsequent activation of the AKT-MTOR signaling pathway (PubMed:24187137). Negatively regulates the differentiation of osteoblasts, potentially via sequestering BMP2, and thereby inhibits the activation of SMAD signaling (PubMed:34002695). The reduction in BMP2 signaling in osteoblasts also results in an increase in expression of the osteoclastogenesis-promoting factors TNFSF11/RANKL and SOST, thereby indirectly promotes bone resorption (PubMed:34002695).|||Mice are viable and fertile without any abnormal phenotypic features in normal conditions (PubMed:24880340, PubMed:30566056). Following hemorrhage mice show decreased hemoglobin and exhibit a delay in recovery from blood loss, rapid suppression of Hamp/hepcidin is also compromised (PubMed:24880340). Loss of Epo-induced enhancement of erythropoiesis and reduction in Epo-mediated suppression of Hamp and Bmp-target gene transcription, however there is no change in baseline HAMP expression (PubMed:30097509). Significantly reduced whole body, femur and tibia bone mass density (BMD) at 6 weeks and 5 months of age. Increases the mineralizing surface, mineral apposition rate and bone formation rates at 6 weeks of age however no differences are seen at 5 months of age (PubMed:34002695). Increase in osteoclast surface and osteoclast number in femurs of 6 week old mice and 5 month old mice (PubMed:34002695). Increase in Bmp2 levels in the serum and secreted by cultured osteoblasts resulting in activation of Bmp2-mediated signaling pathway targets such as Smad1, Smad5, Smad8, and Erk (PubMed:34002695). Stromal cells from 5 month old mice show enhanced ability to differentiate into mature mineralizing colony forming units ex vivo, this results in increased expression of Runx2, Sp7, Sost, and Tnfsf11/Rankl (PubMed:34002695). In an ischemic reperfusion injury model, there is a significance increase in the area and amount of left ventricular damage, resulting in an increase in left ventricular dysfunction and a reduced ejection fraction (PubMed:30566056). Increase in the number of apoptotic cells in the myocardium of the area at risk (PubMed:30566056). Increase in pro-inflammatory markers Tnf, Il-6 and Ccl2/Mcp-1, the macrophage marker Agre1, and the autophagy marker Lc3II/Lc3I ratio (PubMed:30566056). Decrease in phosphorylation of Akt and Creb1 and abolishes the increase of sphingosine-1-phosphate (S1P) and cAMP levels in cardiomyocytes (PubMed:30566056).|||Mice with thalassemia intermedia show high levels of Erfe expression, contributing to the suppression of hepcidin and the systemic iron overload characteristic of thalassemia (Probable). May have cardiac protective functions following ischemic reperfusion injury, which are enhanced by exercise-induced expression and secretion from skeletal muscle. Erfe in the blood may act on cardiomyocytes to reduce apoptosis and macrophage inflammation following injury and therefore limit the subsequent area and amount of damage (PubMed:30566056).|||N-glycosylated; required for secretion of the mature protein.|||Secreted|||Up-regulated by intracellular increase in cAMP levels, such as those elicited by forskolin and epinephrine treatments, and increase in calcium (ionomycine) (PubMed:22351773). Up-regulated by exercise in skeletal muscle (at protein level) and blood plasma (at protein level) (PubMed:22351773, PubMed:30566056). Drastically down-regulated by fasting (PubMed:22351773, PubMed:24187137). Up-regulated in skeletal muscle by refeeding; the extent of induction by refeeding may be dependent upon the muscle fiber type, being much higher in soleus than in plantaris (PubMed:22351773). Both glucose and lipid are equally potent in this induction, in the absence of any gut-derived hormones (PubMed:22351773). Induced by glucose in the blood; following 24 hours fasting (PubMed:22351773). Induced by glucose and/or amino acids in myotubes (PubMed:24187137). Highly induced within 4 hours of bleeding (PubMed:24880340). Induced by Epo in the spleen and blood (PubMed:24880340, PubMed:31800957). http://togogenome.org/gene/10090:Efr3b ^@ http://purl.uniprot.org/uniprot/Q6ZQ18 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EFR3 family.|||Cell membrane|||Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, EFR3B probably acts as the membrane-anchoring component. Also involved in responsiveness to G-protein-coupled receptors; it is however unclear whether this role is direct or indirect.|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2).|||Palmitoylated at its N-terminus, anchoring the protein to the plasma membrane.|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Gal3st1 ^@ http://purl.uniprot.org/uniprot/Q9JHE4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the galactose-3-O-sulfotransferase family.|||Catalyzes the transfer of a sulfate group to position 3 of non-reducing beta-galactosyl residues in glycerolipids and sphingolipids, therefore participates in the biosynthesis of sulfoglycolipids (PubMed:11917099). Catalyzes the synthesis of galactosylceramide sulfate (sulfatide), a major lipid component of the myelin sheath and of monogalactosylalkylacylglycerol sulfate (seminolipid), present in spermatocytes (PubMed:11917099). Seems to prefer beta-glycosides at the non-reducing termini of sugar chains attached to a lipid moiety. Also acts on lactosylceramide, galactosyl 1-alkyl-2-sn-glycerol and galactosyl diacylglycerol (in vitro) (By similarity).|||Expressed in brain, testis, kidney, stomach, small intestine, liver, and lung. Not detected in heart, skeletal muscle, and spleen.|||Golgi apparatus membrane|||Mice homozygous for a null mutation of the CST gene born healthy and display hindlimb weakness from week 6 of age and subsequently show a prenounced tremor and progressive ataxia. Myelin vacuolation is observed in the cerebellar white matter, diencephalon, brainstem and spinal anterior column. Male mice were infertile due to a blocked spermatogenesis. http://togogenome.org/gene/10090:Rdh10 ^@ http://purl.uniprot.org/uniprot/Q8VCH7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Detected in retinal pigment epithelium (at protein level).|||Endoplasmic reticulum membrane|||First detected in the neural groove at 8.0 dpc. At 8.5 dpc, detected in lateral plate mesoderm, the dorsal region of the somites, the floor plate of the neural tube and in head mesenchyme. At 9.5 dpc, detected in dorsal paraxial mesoderm, lateral plate mesoderm and in nephrogenic cord tissues. At 10.5 dpc, detected in lung buds, developing mesonephros, mesodermal tissue surrounding dorsal root ganglia and adjacent to the forlimb buds.|||Microsome membrane|||Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinol to all-trans-retinal. Has no detectable activity towards 11-cis-retinol, 9-cis-retinol and 13-cis-retinol (By similarity). Required for normal embryonic development. http://togogenome.org/gene/10090:Acin1 ^@ http://purl.uniprot.org/uniprot/Q9JIX8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells (By similarity).|||Found in a mRNA splicing-dependent exon junction complex (EJC). Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) complexes consisting of RNPS1, SAP18 and different isoforms of ACIN1; the association of SAP18 seems to require a preformed RNPS1:ACIN1 complex. Interacts with API5. Interacts with SRPK2 in a phosphorylation-dependent manner (By similarity).|||Nucleus|||Nucleus speckle|||Phosphorylation on Ser-1179 by SRPK2 up-regulates its stimulatory effect on cyclin A1.|||Undergoes proteolytic cleavage; the processed form is active, contrary to the uncleaved form.|||nucleoplasm http://togogenome.org/gene/10090:Vmn1r39 ^@ http://purl.uniprot.org/uniprot/G3UWE6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5ae1 ^@ http://purl.uniprot.org/uniprot/Q7TS13 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Armcx3 ^@ http://purl.uniprot.org/uniprot/Q8BHS6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eutherian X-chromosome-specific Armcx family.|||Cytoplasm|||Highly expressed in the developing neural tissues, neural crest derivatives and hind limbs. Also widely expressed in the adult nervous tissue, especially in the forebrain, including the cerebral cortex, hippocampus and thalamus.|||Interacts (via ARM domain) with MIRO1, MIRO2 and TRAK2. The interaction with Miro is calcium-dependent (PubMed:22569362). Interacts with Sox10 (PubMed:19304657).|||Mitochondrion outer membrane|||Nucleus|||Regulates mitochondrial aggregation and transport in axons in living neurons (PubMed:22569362, PubMed:23844091). May link mitochondria to the Trak2-kinesin motor complex via its interaction with Miro and Trak2 (PubMed:22569362). Mitochondrial distribution and dynamics is regulated through Armcx3 protein degradation, which is promoted by PCK and negatively regulated by Wnt1 (PubMed:23844091). Enhances the Sox10-mediated transactivation of the neuronal acetylcholine receptor subunit alpha-3 and beta-4 subunit gene promoters (PubMed:19304657). http://togogenome.org/gene/10090:Cct2 ^@ http://purl.uniprot.org/uniprot/P80314|||http://purl.uniprot.org/uniprot/Q542X7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG. Interacts with FLCN (By similarity). Interacts with DLEC1 (By similarity).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||The N-terminus is blocked. http://togogenome.org/gene/10090:Dazap1 ^@ http://purl.uniprot.org/uniprot/Q9JII5 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-150 is predominantly observed in the nuclear fraction, and may regulate nucleocytoplasmic transport.|||Cytoplasm|||First expressed in midpachytene spermatocytes in stage VII tubules.|||Interacts with DAZ and DAZL.|||Mainly expressed in testis. Expressed at much lower level in liver, heart and brain. Also expressed in ovary. Expressed throughout testes development, in both the prenatal and postnatal periods.|||Nucleus|||RNA-binding protein, which may be required during spermatogenesis. http://togogenome.org/gene/10090:Or13c25 ^@ http://purl.uniprot.org/uniprot/Q8VGA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chd5 ^@ http://purl.uniprot.org/uniprot/E9PYL1|||http://purl.uniprot.org/uniprot/E9PYU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SNF2/RAD54 helicase family.|||Nucleus http://togogenome.org/gene/10090:H2-D1 ^@ http://purl.uniprot.org/uniprot/P01899|||http://purl.uniprot.org/uniprot/Q792Z7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin). Interacts with murid herpesvirus 4 protein K3 (mK3).|||Involved in the presentation of foreign antigens to the immune system.|||Membrane|||Polyubiquitinated in case of infection by murid herpesvirus 4, by the viral E3 ligase K3 (mK3). This modification causes the protein to be targeted for rapid degradation by the endoplasmic reticulum-associated degradation (ERAD) system. Ubiquitination occurs on lysine, as well as serine and threonine residues present in the cytoplasmic tail. Serine and threonine residues are subject to ubiquitination via ester bonds instead of the usual isopeptide linkage. http://togogenome.org/gene/10090:Acnat2 ^@ http://purl.uniprot.org/uniprot/Q8BGG9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acyltransferase which efficiently conjugates very long-chain and long-chain fatty acids to taurine. Shows no conjugation activity in the presence of glycine (By similarity).|||Belongs to the C/M/P thioester hydrolase family.|||Peroxisome http://togogenome.org/gene/10090:Spag1 ^@ http://purl.uniprot.org/uniprot/Q80ZX8 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Antibodies against SPAG1 interfere with fertilization.|||Cytoplasm|||Detected in cerebellum, tongue, esophagus, forestomach, sperm and testis.|||Dynein axonemal particle|||Expression is very low in embryonic epidermis at 13.5 dpc and increases from 14.5 dpc to 16.5 dpc. In young mice expression increases in the testis of 2 to 6 weeks old animals, and then remains stable.|||May play a role in the cytoplasmic assembly of the ciliary dynein arms (By similarity). May play a role in fertilization. Binds GTP and has GTPase activity (By similarity). http://togogenome.org/gene/10090:Cnr2 ^@ http://purl.uniprot.org/uniprot/P47936 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed by cells of hematopoietic origin. Expressed in skin in suprabasal layers and hair follicles, in brain by neurons and glial cells and by osteoblasts, osteocytes, osteoclasts (at protein level).|||Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.|||Mutant mice are responsive to the psychotropic effects of cannabinoid but not to the cannabinoid-induced immunomodulation. They also show accelerated age-related trabecular bone loss and cortical expansion.|||Perikaryon|||dendrite http://togogenome.org/gene/10090:Anp32e ^@ http://purl.uniprot.org/uniprot/P97822 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ANP32 family.|||Component of a SWR1-like complex, composed of EP400, KAT5/TIP60, TRRAP, BRD8, RUVBL1, RUVBL2, ING3 and ANP32E; the complex does not contain SRCAP. Interacts with H2A.Z/H2AZ1 (By similarity). Interacts with the importin alpha KPNA1 and KPNA2.|||Cytoplasm|||Expressed at highest levels in cerebellum and spleen. In the cerebellum, expressed mainly in granule cells and, to a lesser extent, in Purkinje cells.|||Histone chaperone that specifically mediates the genome-wide removal of histone H2A.Z/H2AZ1 from the nucleosome: removes H2A.Z/H2AZ1 from its normal sites of deposition, especially from enhancer and insulator regions. Not involved in deposition of H2A.Z/H2AZ1 in the nucleosome. May stabilize the evicted H2A.Z/H2AZ1-H2B dimer, thus shifting the equilibrium towards dissociation and the off-chromatin state (PubMed:24463511). Inhibits activity of protein phosphatase 2A (PP2A). Does not inhibit protein phosphatase 1. May play a role in cerebellar development and synaptogenesis.|||Low levels are found at postnatal day 4. Levels increase from postnatal day 7 to postnatal day 17. Levels decrease and remain low in the adult.|||No visible phenotype. Mice are viable and fertile (PubMed:20844742, PubMed:21049064, PubMed:23675506). They display a subtle neurological clasping phenotype and mild motor deficits (PubMed:20844742). Motor defects were not confirmed by a subsequent analysis (PubMed:23675506). Deletion in embryonic fibroblasts results in the appearance of a significant number of new H2A.Z/H2AZ1 around the transcription start site as well as at other chromatin regions (PubMed:24463511).|||Nucleus|||Phosphorylated. The phosphorylation is nuclear localization signal (NLS)-dependent (By similarity).|||The H2A.Z-interacting domain (ZID) mediates a direct interaction with H2A.Z/H2AZ1. http://togogenome.org/gene/10090:Denr ^@ http://purl.uniprot.org/uniprot/Q9CQJ6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the DENR family.|||Interacts with MCTS1.|||May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits (By similarity). http://togogenome.org/gene/10090:Taf1 ^@ http://purl.uniprot.org/uniprot/B1Q2W7|||http://purl.uniprot.org/uniprot/Q80UV9 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylates on Ser residues. Inhibited by retinoblastoma tumor suppressor protein, RB1. Binding to TAF1 or CIITA inhibits the histone acetyltransferase activity.|||Belongs to the TAF1 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs) (PubMed:10438527). TFIID consists of at least TBP, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts with TAF7; the interaction is direct. TAF1, when part of the TFIID complex, interacts with C-terminus of TP53. Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. RB1 interacts with the N-terminal domain of TAF1. Interacts with ASF1A and ASF1B. Interacts (via bromo domains) with acetylated lysine residues on the N-terminus of histone H1.4, H2A, H2B, H3 and H4 (in vitro) (By similarity).|||Nucleus|||Phosphorylated by casein kinase II in vitro.|||The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions. The second domain also recognizes and binds histones that are butyrylated and crotonylated.|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (By similarity). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (By similarity). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (By similarity). TAF1 is the largest component and core scaffold of the TFIID complex, involved in nucleating complex assembly (PubMed:10438527). TAF1 forms a promoter DNA binding subcomplex of TFIID, together with TAF7 and TAF2 (By similarity). Contains novel N- and C-terminal Ser/Thr kinase domains which can autophosphorylate or transphosphorylate other transcription factors (By similarity). Phosphorylates TP53 on 'Thr-55' which leads to MDM2-mediated degradation of TP53 (By similarity). Phosphorylates GTF2A1 and GTF2F1 on Ser residues (By similarity). Possesses DNA-binding activity (By similarity). Exhibits histone acetyltransferase activity towards histones H3 and H4 (By similarity). Essential for progression of the G1 phase of the cell cycle (By similarity). http://togogenome.org/gene/10090:Hvcn1 ^@ http://purl.uniprot.org/uniprot/Q3U2S8 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hydrogen channel family.|||Cell membrane|||Enriched in immune tissues, such as bone marrow, macrophages and spleen.|||Homodimer.|||Mediates the voltage-dependent proton permeability of excitable membranes. Forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient. Proton efflux, accompanied by membrane depolarization, facilitates acute production of reactive oxygen species in phagocytosis.|||Membrane|||Phosphorylation may enhance channel gating.|||The C-terminal coiled coil region mediates homodimerization and cooperative channel gating. It is essential for normal subcellular localization.|||The dimers display cooperative channel gating. The channel activity is inhibited by zinc ions.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Unlike other voltage-gated ion channels it lacks the pore domain. http://togogenome.org/gene/10090:Grpel2 ^@ http://purl.uniprot.org/uniprot/O88396|||http://purl.uniprot.org/uniprot/Q0VB85 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GrpE family.|||Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner.|||Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins. Stimulates ATPase activity of mt-HSP70. May also serve to modulate the interconversion of oligomeric (inactive) and monomeric (active) forms of mt-HSP70.|||Mitochondrion matrix|||Probable component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPEL1 or GRPEL2, TIMM44, TIMM16/PAM16 and TIMM14/DNAJC19.|||Ubiquitous. http://togogenome.org/gene/10090:Gabrb3 ^@ http://purl.uniprot.org/uniprot/P63080|||http://purl.uniprot.org/uniprot/Q8C446 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB3 sub-subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (By similarity). Can form functional homopentamers (in vitro) (By similarity). Interacts with UBQLN1 (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (PubMed:28978485). Interacts with GIT1; this interaction is required for synaptic GABRB3 surface stability and inhibitory synapse strength (By similarity).|||Important perinatal lethality. About 57% of the pups have a cleft palate. About 90% of the pups die within 24 hours after birth, including 30% of those that do not have a cleft palate. Surviving mice are runted until weaning, but attain normal body weight in adulthood. They are hyperactive and display behavorial abnormalities. They do not display jerky gait, but have difficulty with swimming, walking on grids, and avoiding to fall from rotarods. Mutant mice are fertile, but females do not display normal nurturing behavior. Mutant mice have abnormal electroencephalograms (EEGs) and tend to suffer from seizures. Brains from mutant mice show strongly reduced numbers of GABA and benzodiazepine receptors. Neurons from dorsal root ganglion show a decrease of about 80% of GABA-induced chloride currents. In addition, mutant mice have an average lifespan of about 18 weeks, instead of the expected 127 weeks (PubMed:9108119). Mutant mice display a lowered threshold to nociception and are abnormally sensitive to touch and heat stimuli. GABA receptor agonists have decreased antinociceptive effects in mutant mice (PubMed:10670447).|||Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:9108119). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA- gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta3/gamma2 receptor exhibits synatogenic activity whereas the alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (PubMed:27129275). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity). Plays an important role in somatosensation and in the production of antinociception (PubMed:10670447).|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Derl3 ^@ http://purl.uniprot.org/uniprot/Q14C34|||http://purl.uniprot.org/uniprot/Q9D8K3 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the derlin family.|||Endoplasmic reticulum membrane|||Expressed in neural cells during enbryogenesis. From 11.5 dpc until 14.5 dpc, it is mainly expressed in the forebrain. From 15.5 dpc until birth, expression in the forebrain becomes weaker but is still observed in the olfactory bulb and the skin around the eyes, nose, limbs and tail, showing that its pattern of expression changes from the central nervous system to the peripheral tissues during development.|||Forms homo- and heterooligomers with DERL2 and, to a lesser extent, with DERL1 (By similarity). Interacts with VCP and EDEM1 (By similarity). Interacts with SELENOK and SELENOS (PubMed:22016385). Interacts with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control (By similarity).|||Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins. May act by forming a channel that allows the retrotranslocation of misfolded glycoproteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the misfolded glycoproteins. May be involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation.|||Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome.|||Highly expressed in spleen, lung, liver, spleen and testis. Expressed at intermediate level in kidney. Weakly or not expressed in brain, heart and skeletal muscle.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Bmpr1b ^@ http://purl.uniprot.org/uniprot/B2RRZ4|||http://purl.uniprot.org/uniprot/P36898|||http://purl.uniprot.org/uniprot/Q3USS1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Interacts with high affinity with GDF5; positively regulates chondrocyte differentiation (By similarity). Interacts with SCUBE3 (By similarity). Interacts with TSC22D1/TSC-22 (By similarity).|||Membrane|||On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP7/OP-1. Receptor for GDF5 (PubMed:26105076, PubMed:19229295). Positively regulates chondrocyte differentiation through GDF5 interaction (PubMed:24098149). http://togogenome.org/gene/10090:Herpud2 ^@ http://purl.uniprot.org/uniprot/Q9JJC9 ^@ Function|||Subcellular Location Annotation ^@ Could be involved in the unfolded protein response (UPR) pathway.|||Membrane http://togogenome.org/gene/10090:Cbll1 ^@ http://purl.uniprot.org/uniprot/Q9JIY2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Hakai family.|||Cytoplasm|||Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1 (PubMed:11836526, PubMed:22252131). Targets CDH1 for endocytosis and degradation (PubMed:11836526). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29535189, PubMed:29547716). Its function in the WMM complex is unknown (PubMed:29535189, PubMed:29547716).|||Homodimer (PubMed:22252131). Interacts with tyrosine-phosphorylated SRC substrates (PubMed:11836526, PubMed:22252131). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (By similarity).|||Nucleus speckle|||Phosphorylated on tyrosine residues.|||The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids.|||nucleoplasm http://togogenome.org/gene/10090:Hs3st3a1 ^@ http://purl.uniprot.org/uniprot/Q52KJ0|||http://purl.uniprot.org/uniprot/Q8BKN6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 1 family.|||Golgi apparatus membrane|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to an N-unsubstituted glucosamine linked to a 2-O-sulfo iduronic acid unit on heparan sulfate. Catalyzes the O-sulfation of glucosamine in IdoUA2S-GlcNS and also in IdoUA2S-GlcNH2. Unlike HS3ST1/3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate (By similarity). http://togogenome.org/gene/10090:Adamts2 ^@ http://purl.uniprot.org/uniprot/Q8C9W3 ^@ Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Cleaves the propeptides of type I and II collagen prior to fibril assembly (By similarity). Does not act on type III collagen (By similarity). Cleaves lysyl oxidase LOX at a site downstream of its propeptide cleavage site to produce a short LOX form with reduced collagen-binding activity (By similarity).|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||May belong to a multimeric complex. Binds specifically to collagen type XIV (By similarity).|||The precursor is cleaved by a furin endopeptidase.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Krt14 ^@ http://purl.uniprot.org/uniprot/Q61781 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A disulfide bond is formed between rather than within filaments and promotes the formation of a keratin filament cage around the nucleus.|||Belongs to the intermediate filament family.|||Cytoplasm|||Expressed in the corneal epithelium (at protein level) (PubMed:26758872). Expressed in the basal layer of the epidermis and the outer root sheath of hair follicles (at protein level) (PubMed:11408584). Expressed in the epithelial basal layer in the tail epidermis (PubMed:2433272). Expressed in the parabasal cell row, basal cell layer, and suprabasal epithelial layer of the tongue (PubMed:2433272).|||Expressed in the epithelial cells of the tongue and palate at 17 dpc (PubMed:2433272). Expressed in ameloblasts at the periphery and at the incisal region of mandibular molars at P3 (PubMed:12657653). Expressed at the Tomes' processes of ameloblasts at the incisal region at P5 (PubMed:12657653). Expression at the incisal region decreased at P7 and P9 (PubMed:12657653).|||Heterotetramer of two type I and two type II keratins (PubMed:22705788). Forms a disulfide-linked heterodimer (via 2B domains) with KRT5 (via 2B domains) (PubMed:22705788, PubMed:24940650). Forms a heterodimer with KRT1; the interaction is more abundant in the absence of KRT5 (PubMed:11408584). Interacts with PLEC isoform 1C, when in a heterodimer with KRT5 (PubMed:24940650). Interacts with TRADD and with keratin filaments (PubMed:16702408). Associates with other type I keratins (By similarity). Interacts with EPPK1 (PubMed:18285451). Interacts with KLHL24 (By similarity). Interacts with PKP1 (via N-terminus) and PKP2 (By similarity).|||Increase in CXCL16 abundance in the epidermis at 2 days of age.|||Nucleus|||The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filaments in vitro.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||Ubiquitinated by the BCR(KLHL24) E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Mtfr2 ^@ http://purl.uniprot.org/uniprot/Q8VED8|||http://purl.uniprot.org/uniprot/Q9D0I1|||http://purl.uniprot.org/uniprot/Q9D456 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MTFR1 family.|||Expressed predominantly in testis (at protein level). Expressed to a lower extent in spleen.|||May play a role in mitochondrial aerobic respiration essentially in the testis. Can also promote mitochondrial fission.|||Mitochondrion|||Plays a role in mitochondrial aerobic respiration. Regulates mitochondrial organization and fission. http://togogenome.org/gene/10090:Cmpk1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J093|||http://purl.uniprot.org/uniprot/Q9DBP5 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylate kinase family. UMP-CMP kinase subfamily.|||Binds 1 Mg(2+) ion per monomer.|||Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity.|||Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis.|||Cytoplasm|||Monomer.|||Nucleus http://togogenome.org/gene/10090:Ttc7b ^@ http://purl.uniprot.org/uniprot/E9Q6P5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions.|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2). Interacts with PI4KA, interaction is direct. Interacts with EFR3 (EFR3A or EFR3B), interaction is direct. Interacts with HYCC (HYCC1 or HYCC2), interaction is direct. Association with the PI4K complex is strongly reduced by TMEM150A.|||cytosol http://togogenome.org/gene/10090:Nuak2 ^@ http://purl.uniprot.org/uniprot/Q8BZN4 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity ^@ Activated by phosphorylation on Thr-220.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||First expressed in the anterior neuroectoderm at 7.5 dpc. At 8.5 dpc, the expression is present in future forebrain and midbrain regions. At 9.5 dpc, the expression is intense in the forebrain and midbrain with a sharp caudal boundary at the isthmic region; a low level of the expression is found throughout the neuroectoderm. Not expressed in the ventral body wall.|||Phosphorylated at Thr-220 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Autophosphorylation is also possible at Thr-220.|||Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway. http://togogenome.org/gene/10090:Hdhd3 ^@ http://purl.uniprot.org/uniprot/Q9CYW4 ^@ Similarity ^@ Belongs to the HAD-like hydrolase superfamily. http://togogenome.org/gene/10090:Or5an10 ^@ http://purl.uniprot.org/uniprot/A0PK57 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sfn ^@ http://purl.uniprot.org/uniprot/O70456 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 14-3-3 proteins have been shown to be PKC activators, but this effect could be non-specific and only due to the acidic nature of the protein.|||Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway. May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53.|||Belongs to the 14-3-3 family.|||Cytoplasm|||Expressed in the basal layer of skin epithelium and in outer root sheath of hair follicle.|||Homodimer. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29 and VPS35. Interacts with GAB2 (By similarity). Interacts with KRT17. Interacts with SAMSN1. Interacts with SRPK2 (By similarity). Interacts with COPS6 (By similarity). Interacts with COP1; this interaction leads to proteasomal degradation (By similarity).Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB (By similarity). Interacts with SLITRK1 (By similarity). Interacts with LRRK2; this interaction is dependent on LRRK2 phosphorylation (By similarity).|||Induced in damaged or stressed epidermis.|||Nucleus|||Secreted|||Ubiquitinated. Ubiquitination by RFFL induces proteasomal degradation and indirectly regulates p53/TP53 activation (By similarity). http://togogenome.org/gene/10090:Tdp1 ^@ http://purl.uniprot.org/uniprot/B8JJC1|||http://purl.uniprot.org/uniprot/Q6P1B8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tyrosyl-DNA phosphodiesterase family.|||Nucleus http://togogenome.org/gene/10090:Or8b3 ^@ http://purl.uniprot.org/uniprot/Q60886 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:S100g ^@ http://purl.uniprot.org/uniprot/P97816|||http://purl.uniprot.org/uniprot/Q5VM59 ^@ Similarity ^@ Belongs to the S-100 family. http://togogenome.org/gene/10090:Lce1g ^@ http://purl.uniprot.org/uniprot/Q9D0X3|||http://purl.uniprot.org/uniprot/Q9D195 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Depdc5 ^@ http://purl.uniprot.org/uniprot/P61460 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:31548394). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (By similarity). In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway (By similarity). Within the GATOR1 complex, DEPDC5 mediates direct interaction with the nucleotide-binding pocket of small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and coordinates their nucleotide loading states by promoting RagA/RRAGA or RagB/RRAGB into their GDP-binding state and RagC/RRAGC or RagD/RRAGD into their GTP-binding state (By similarity). However, it does not execute the GAP activity, which is mediated by NPRL2 (By similarity).|||Belongs to the IML1 family.|||Expressed at low levels in all brain regions. Expressed throughout brain development, including in midgestation embryonic head (11.5 dpc), neonatal brain and whole adult brain. Present in neurons and absent in non-neuronal cells, including astrocytes (at protein level).|||Lysosome membrane|||Phosphorylation at Ser-992 and Ser-1518 by AKT1 and PIM1 inhibit the activity of DEPDC5, releasing inhibition of the mTORC1 pathway.|||The DEP domain mediates the interaction with KLHL22.|||Ubiquitinated. Amino acid-induced 'Lys-48'-linked polyubiquitination of DEPDC5 by the BCR(KLHL22) ubiquitin ligase complex leads to DEPDC5 proteasomal degradation and inhibition of the GATOR1 complex. Ubiquitination may occur at multiple lysines.|||Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction of the GATOR complex with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) heterodimers. GATOR1 interacts with GPR155/LYCHOS; interaction takes place in presence of cholesterol and prevents interaction between GATOR1 and KICSTOR. Interacts with BMT2/SAMTOR; interaction is direct and takes place in presence of methionine, leading to inhibit the activity of the GATOR1 complex.|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Rab8a ^@ http://purl.uniprot.org/uniprot/P55258 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasm|||Golgi apparatus|||Interacts (GTP-bound form) with MICALL1; regulates RAB8A association with recycling endosomes (PubMed:18094055). Interacts with MICALL2; competes with RAB13 and is involved in E-cadherin endocytic recycling (PubMed:18094055). Interacts (GTP-bound form) with MICAL1, MICALCL, MICAL3 and EHBP1L1; two molecules of RAB8A can bind to one molecule of the effector protein; ternary complexes of RAB8A, RAB13 and either MICAL1 or EHBP1L1 are possible (By similarity). Interacts (GTP-bound form) with EHBP1 (By similarity). Interacts with EHD1 (By similarity). Interacts with MAP4K2 and SYTL4 (PubMed:8643544, PubMed:12590134). Interacts with SGSM1 and SGSM3 (PubMed:17509819). Interacts with RABIF, RIMS2, RPH3A and RPH3A (PubMed:12578829, PubMed:16541104). Interacts with OPTN (By similarity). Interacts with RAB3IP (PubMed:19625297). Interacts with MYO5B (By similarity). Interacts with CIMAP3 (PubMed:20643351). Interacts with BIRC6/bruce (By similarity). Interacts with OCRL (By similarity). Interacts with AHI1 (PubMed:19625297). Interacts with DCDC1 (By similarity). Interacts with LRRK2; interaction facilitates phosphorylation of Thr-72 (By similarity). Interacts with RAB31P, GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, TBC1D15 and INPP5B; these interactions are dependent on Thr-72 not being phosphorylated (By similarity). Interacts with RILPL1 and RILPL2; these interactions are dependent on the phosphorylation of Thr-72 by LRRK2 (PubMed:29125462). Interacts with DZIP1; prevents inhibition by the GDP-dissociation inhibitor GDI2 (PubMed:25860027).|||Midbody|||Phosphorylation of Thr-72 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||Recycling endosome membrane|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase (By similarity). Activated in response to insulin (By similarity).|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (By similarity). Regulates the compacted morphology of the Golgi (By similarity). Together with MYO5B and RAB11A participates in epithelial cell polarization (By similarity). Also involved in membrane trafficking to the cilium and ciliogenesis (PubMed:25860027). Together with MICALL2, may also regulate adherens junction assembly (PubMed:18094055). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (By similarity).|||centriole|||cilium|||cilium basal body|||phagosome membrane http://togogenome.org/gene/10090:Or8g36 ^@ http://purl.uniprot.org/uniprot/Q9EQB7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gem ^@ http://purl.uniprot.org/uniprot/P55041|||http://purl.uniprot.org/uniprot/Q3TH76 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. RGK family.|||By mitogens.|||Cell membrane|||Could be a regulatory protein, possibly participating in receptor-mediated signal transduction at the plasma membrane. Has guanine nucleotide-binding activity but undetectable intrinsic GTPase activity.|||Interacts with calmodulin in a Ca(2+)-dependent manner. Calmodulin binding significantly decreases GTP binding. Binds ROCK1 (By similarity).|||Phosphorylated on tyrosine residues. http://togogenome.org/gene/10090:Oog4 ^@ http://purl.uniprot.org/uniprot/Q4G0C7|||http://purl.uniprot.org/uniprot/Q8BHX9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Radil ^@ http://purl.uniprot.org/uniprot/Q69Z89 ^@ Function|||Similarity|||Subunit ^@ Belongs to the RADIL family.|||Downstream effector of Rap required for cell adhesion and migration of neural crest precursors during development.|||Interacts with RAP1A; in a GTP-dependent manner. Does not interact with members of the Ras family. Interacts (via PDZ domain) with KIF14; is recruited to the microtubule network restricting its interaction with activated RAP1A (By similarity). http://togogenome.org/gene/10090:Fam166b ^@ http://purl.uniprot.org/uniprot/A2AIP0|||http://purl.uniprot.org/uniprot/E9Q4G6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CIMIP2 family.|||Expressed in airway epithelial cells.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Glrx3 ^@ http://purl.uniprot.org/uniprot/Q9CQM9 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Homodimer; the homodimer is independent of 2Fe-2S clusters. Heterotrimer; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters. Interacts (via N-terminus) with PRKCQ/PKC-theta (By similarity). Interacts (via C-terminus) with CSRP3 (PubMed:18258855). Interacts with CSRP2 (PubMed:18258855).|||Homozygous null mutants die in utero some time between 12.5 and 14.5 dpc. 12.5 dpc embryos have a smaller body size and hemorrhage in the head. Heterozygous mutants are fertile and show no abnormalities in growth and development, cardiomyocytes exhibit significantly reduced contractility.|||The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.|||Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (By similarity). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (PubMed:16809552, PubMed:18258855, PubMed:18929570). Required for hemoglobin maturation. Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity (By similarity).|||Transgenic mice with cardiac-specific Glrx3 overexpression show that it is a potent inhibitor of cardiac hypertrophy induced by pressure overload (transverse aortic constriction). In addition, overexpression dramatically increases the ventricular function and cardiomyocyte contractility.|||Z line|||cell cortex|||cytosol http://togogenome.org/gene/10090:Mecr ^@ http://purl.uniprot.org/uniprot/Q9DCS3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.|||Catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis type II). Fatty acid chain elongation in mitochondria uses acyl carrier protein (ACP) as an acyl group carrier, but the enzyme accepts both ACP and CoA thioesters as substrates in vitro. Displays a preference for medium-chain over short- and long-chain substrates (By similarity). May provide the octanoyl chain used for lipoic acid biosynthesis, regulating protein lipoylation and mitochondrial respiratory activity particularly in Purkinje cells (PubMed:30266742).|||Expressed in Purkinje cells (at protein level).|||Homodimer.|||Homozygous deficiency causes placental insufficiency and embryonic lethality between 9.5 and 11.5 dpc.|||Mitochondrion http://togogenome.org/gene/10090:Ebf4 ^@ http://purl.uniprot.org/uniprot/B2RQX3|||http://purl.uniprot.org/uniprot/Q8K4J2 ^@ Caution|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apparently no differences in the NK, CD8(+), and CD4(+) precursor and mature cell subsets in the thymus, spleen, or liver.|||Belongs to the COE family.|||EBF4 is expressed in human NK cells and CD8(+) T-cells (PubMed:35939714). It has been suggested, therefore, that the functions of EBF4 differ between humans and mice (PubMed:35939714).|||Expressed in the olfactory epithelium, including in both neuronal and basal cell layers (PubMed:12139918, PubMed:35939714). Absent in the vomeronasal organ (PubMed:12139918). Absent from NK cells and CD8(+) T cells (PubMed:35939714).|||Forms either a homodimer or a heterodimer with a related family member.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Transcription factor (PubMed:12139918). Positively modulates transcription, perhaps less strongly than other early B cell factor/EBF family proteins (PubMed:12139918). Binds an EBF1/Olf-1 consensus site in vitro (PubMed:12139918). http://togogenome.org/gene/10090:Cbln1 ^@ http://purl.uniprot.org/uniprot/Q9R171 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed and secreted by presynaptic neurons, such as cerebellar granule cells. Following secretion, the protein binds to GRID2 on the postsynaptic Purkinje cell membranes. Expressed at the highest level in the cerebellar cortex. High levels are also seen in the olfactory bulb, posterior part of the cerebral cortex, certain thalamic nuclei, and deep cerebellar nuclei. Low to moderate levels are detected in some hypothalamic and brainstem nuclei. In the thalamus, expressed in parafascicular nucleus neurons and other regions (at protein level).|||Homohexamer; disulfide-linked homotrimers. The trimers are assembled via the globular C1q domains. The trimers associate via N-terminal cysteine residues to form disulfide-linked hexamers (PubMed:16135095). May form oligomers with CBLN2, CBLN3 and CBLN4 prior to secretion (PubMed:29782851). Once secreted, does not interact with other CBLN family members (PubMed:17030622, PubMed:17331201, PubMed:10964938). Interacts with GRID1 (PubMed:22220752). Interacts with NRXN1 and NRXN2 long (alpha) and short (beta) isoforms produced by alternative promoter usage (PubMed:21410790, PubMed:22220752, PubMed:29782851). Competes with NLGN1 for NRXN1-binding. Weakly interacts with NRXN3 short isoform and not at all with NRXN3 long isoform (PubMed:21410790, PubMed:22220752, PubMed:29782851). Interacts (via C1q domain) with GRID2; GRID2-binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal domain dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:20395510, PubMed:21410790, PubMed:22220752, PubMed:29782851). Interacts with OTOL1 (PubMed:20856818).|||In the developing brain, expressed as early as embryonic day 10-13, and transiently up-regulated during the late embryonic and neonatal periods. Cerebellin and [des-Ser1]-cerebellin are expressed as easly as postnatal day 3-4. The levels of both peptides rise rapidly to a maximum at approximately day 25-30 after birth, whereafter they fall to stable adult values.|||Mice (reeler, weaver and staggerer) show defects in granule cell migration and parallel fiber formation, synaptogenesis, Purkinje cell dendritic maturation and establishment of adult cytoarchitecture show a correlation between the formation and number of parallel fiber-Purkinje cell synapses and cerebellin levels (PubMed:3199194). CBLN1 single knockout mice show a major impairment in motor behaviors (PubMed:3420533). Double CBLN1 and CBLN2 knockout mice exhibit gait abnormalities, impairments in balance and coordination and develop seizures (PubMed:3420533). Synapse density in the hippocampus is normal in 1-2 months old mice, but severely decreased in 6 month old mice (PubMed:3420533). Triple CBLN1, CBLN2 and CBLN4 knockout mice exhibit impairments in sensory processing and sensorimotor gating, in addition to severe motor deficits, seizures and reduced synapse density in the hippocampus of aging mice (PubMed:3420533).|||Postsynaptic cell membrane|||Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the matching and maintenance of pre- and post-synaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and induction of long-term depression at parallel fiber-Purkinje cell synapses (PubMed:16234806). Plays a role as a synaptic organizer that acts bidirectionally on both pre- and post-synaptic components (PubMed:20395510). On the one hand induces accumulation of synaptic vesicles in the pre-synaptic part by binding with NRXN1 and in other hand induces clustering of GRID2 and its associated proteins at the post-synaptic site through association of GRID2 (PubMed:21410790). NRXN1-CBLN1-GRID2 complex directly induces parallel fiber protrusions that encapsulate spines of Purkinje cells leading to accumulation of GRID2 and synaptic vesicles (PubMed:23141067). Required for CBLN3 export from the endoplasmic reticulum and secretion (PubMed:17030622, PubMed:17331201). NRXN1-CBLN1-GRID2 complex mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (By similarity). Essential for long-term maintenance but not establishment of excitatory synapses (PubMed:29691328). Inhibits the formation and function of inhibitory GABAergic synapses in cerebellar Purkinje cells (PubMed:24467251).|||Secreted|||Sialoglycoprotein.|||The cerebellin peptide exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release (By similarity).|||The proteolytic processing to yield cerebellin seems to occur either prior to the secretion by presynaptic neurons and subsequent oligomerization or in some other location after release of the mature protein. In the cerebellum, cerebellin is much more abundant than [des-Ser1]-cerebellin. http://togogenome.org/gene/10090:Cdk14 ^@ http://purl.uniprot.org/uniprot/O35495|||http://purl.uniprot.org/uniprot/Q6NVF8|||http://purl.uniprot.org/uniprot/Q8BFX6 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cell membrane|||Cytoplasm|||Found in a complex with LRP6, CCNY and CAPRIN2 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus. Interacts with CCNY; CCNY mediates its recruitment to the plasma membrane and promotes phosphorylation of LRP6. Interacts with CCDN3 and CDKN1A. Interacts with SEPT8. Interacts with 14-3-3 proteina YWHAB, YWHAE, YWHAH and YWHAQ.|||In the adult, widely expressed at low levels except in brain, kidney and testis where expression is high. In the brain, detected in cortex, hippocampus, dentate gyrus, amygdala cortex, parasubiculum and cerebellum. In the embryo, expressed predominantly in the nervous system.|||In the testis, expressed at low levels in Sertoli cells of 7-day-old mice, barely detected at day 17, and detected at much higher levels in late pachytene/diplotene spermatocytes in the adult. In the nervous system, expressed at highest levels in the adult.|||Nucleus|||Serine/threonine-protein kinase activity is promoted by associated cyclins CCDN3 and CCNY and repressed by CDKN1A.|||Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by mediating the phosphorylation of LRP6 at 'Ser-1490', leading to the activation of the Wnt signaling pathway. Acts as a regulator of cell cycle progression and cell proliferation via its interaction with CCDN3. Phosphorylates RB1 in vitro, however the relevance of such result remains to be confirmed in vivo. May also play a role in meiosis, neuron differentiation and may indirectly act as a negative regulator of insulin-responsive glucose transport (By similarity). http://togogenome.org/gene/10090:Tspan2 ^@ http://purl.uniprot.org/uniprot/Q922J6|||http://purl.uniprot.org/uniprot/Q9D1X8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||May play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath.|||Membrane http://togogenome.org/gene/10090:Rpp25 ^@ http://purl.uniprot.org/uniprot/Q91WE3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone-like Alba family.|||Component of nuclear RNase P and RNase MRP ribonucleoproteins. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5. POP7 forms a heterodimer with RPP25 that binds to the P3 stem loop of the catalytic RNA.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.|||nucleolus http://togogenome.org/gene/10090:Fxyd6 ^@ http://purl.uniprot.org/uniprot/Q9D164 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FXYD family.|||Membrane http://togogenome.org/gene/10090:Rab21 ^@ http://purl.uniprot.org/uniprot/P35282|||http://purl.uniprot.org/uniprot/Q0PD35 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cleavage furrow|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Endosome membrane|||Golgi apparatus membrane|||Interacts with the cytoplasmic tail of integrins ITGA1, ITGA2, ITGA5, ITGA6, ITGA11 and ITGB1; this interaction is dependent upon its GDP/GTP cycle (PubMed:16754960). Interacts with RABGEF1 (via VPS9 domain) (By similarity). Interacts with ANKRD27 (By similarity). Interacts with VAMP7 (By similarity). Interacts (in GTP-bound form) with VAMP8 in response to starvation; the interaction probably regulates VAMP8 endolysosomal trafficking (By similarity). Interacts (active GTP-bound form) with TMED10; the interaction is indirect and regulates TMED10 abundance and localization at the Golgi (By similarity).|||Small GTPase involved in membrane trafficking control (PubMed:16754960, PubMed:18804435). Regulates integrin internalization and recycling, but does not influence the traffic of endosomally translocated receptors in general (PubMed:16754960). As a result, may regulate cell adhesion and migration (PubMed:16754960). During the mitosis of adherent cells, controls the endosomal trafficking of integrins which is required for the successful completion of cytokinesis (PubMed:18804435). Involved in neurite growth (By similarity). Following SBF2/MTMT13-mediated activation in response to starvation-induced autophagy, binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (By similarity). Modulates protein levels of the cargo receptors TMED2 and TMED10, and required for appropriate Golgi localization of TMED10 (By similarity).|||neuron projection|||trans-Golgi network http://togogenome.org/gene/10090:Socs7 ^@ http://purl.uniprot.org/uniprot/Q8VHQ2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Interacts with phosphorylated IRS4 and PIK3R1. Interacts, via the third proline-rich region, with the second SH3 domain of the adapter protein NCK1. Also interacts with GRB2, INSR, IRS1, PLCG1, SORBS3/vinexin and phosphorylated STAT3 and STAT5 (By similarity). Interacts with SEPT6 (By similarity).|||Mice are smaller and half of them develop fatal hydrocephalus between 3 to 15 weeks of age. They display subtle alterations in glucose homeostasis with an enhanced response to insulin which causes hypoglycemia. Pancreatic islets become progressively larger.|||Nucleus|||Regulates signaling cascades probably through protein ubiquitination and/or sequestration. Functions in insulin signaling and glucose homeostasis through IRS1 ubiquitination and subsequent proteasomal degradation. Inhibits also prolactin, growth hormone and leptin signaling by preventing STAT3 and STAT5 activation, sequestering them in the cytoplasm and reducing their binding to DNA. May be a substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).|||The SOCS box domain is required for IRS1 ubiquitination and subsequent proteasomal degradation.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.|||Ubiquitously expressed at low level in 12.5 dpc and 15.5 dpc embryos. More significantly expressed in the nervous system at 12.5 dpc and the cortical plate at 15.5 dpc. Expressed in the brain postnatally in particular in the hippocampal formation and the medial habenular nuclei at P7. Low-level expression in other brain areas was present at P7 and was reduced to very low levels at P14 and P21. The hippocampal granule cell layer and the cerebellar granular layer maintained moderate expression levels at P7, P14, and P21.|||Widely expressed with higher expression in brain and testis where it is expressed by spermatocytes and early spermatids. Also significantly expressed in spleen, skeletal muscle and kidney. http://togogenome.org/gene/10090:Tie1 ^@ http://purl.uniprot.org/uniprot/Q06806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.|||Cell membrane|||Heterodimer with TEK/TIE2.|||Phosphorylated on tyrosine residues in response to ANGPT1, most likely by TEK/TIE2.|||Specifically expressed in developing vascular endothelial cells. Abundantly expressed in lung and heart, moderately in brain, liver and kidney, and weakly in thymus, spleen and testis.|||Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis. http://togogenome.org/gene/10090:Slc20a2 ^@ http://purl.uniprot.org/uniprot/Q80UP8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.|||Brain. In the brain, expressed in the choroid plexus, ependyma and arteriolar smooth muscle cells (at protein level) (PubMed:26822507). Widely expressed including intestine, kidney, heart, liver, testis and skin. Expressed throughout the vertcal crypt-axial axis of intestinal epithelium (PubMed:11003594).|||Cell membrane|||Homodimer.|||Mice develop basal ganglia calcification and display significantly elevated phosphate in cerebral spinal fluid, calcified optic nerve tissue, moderate to severe hydrocephalus, poor skeletal development, low body weight and significantly decreased postweaning survival rates (PubMed:26822507). Juvenile mice exhibit abnormal endochondral and intramembranous ossification, decreased mineral accrual, and short stature (PubMed:30721528). Adults exhibit only small reductions in bone mass and mineralization but a profound impairment of bone strength (PubMed:30721528).|||Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11003594, PubMed:23968976, PubMed:26822507, PubMed:30721528). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (PubMed:30721528). Required to maintain normal cerebrospinal fluid phosphate levels (PubMed:26822507). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (PubMed:23968976). http://togogenome.org/gene/10090:Zfp446 ^@ http://purl.uniprot.org/uniprot/E9Q6F9|||http://purl.uniprot.org/uniprot/Q149D4|||http://purl.uniprot.org/uniprot/Q8C9M8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Akt3 ^@ http://purl.uniprot.org/uniprot/Q9WUA6 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.|||Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane.|||Cytoplasm|||In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.|||Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6 (By similarity). Interacts with KCTD20 (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256).|||Isoform 1 is expressed in prostate, testis, uterus and mammary gland and isoform 2 is expressed in prostate, testis and mammary gland.|||Membrane|||Nucleus|||O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.|||Phosphorylation on Thr-305 and Ser-472 is required for full activity.|||Results in the cytoplasmic accumulation of the master regulator of mitochondrial biogenesis, Ppargc1a, and a reduction in known Ppargc1a target genes, which leads to an abnormal mitochondrial phenotype in the brain tissue.|||Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation. IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.|||Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome (By similarity). http://togogenome.org/gene/10090:Cd300a ^@ http://purl.uniprot.org/uniprot/Q6SJQ0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD300 family.|||Cell membrane|||Inhibitory receptor which may contribute to the down-regulation of cytolytic activity in natural killer (NK) cells, and to the down-regulation of mast cell degranulation (PubMed:12874256, PubMed:12893283, PubMed:16339535). Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 but not TRIF through activation of PTPN6 (By similarity).|||N-glycosylated.|||Phosphorylated on tyrosine.|||Present on the surface of the majority of myeloid cells and a subset of B-cells. Present on the surface of NK cells after IL-12 stimulation.|||Upon tyrosine-phosphorylation, interacts with PTN6/SHP-1 and PTPN11/SHP-2 and INPP5D. http://togogenome.org/gene/10090:Tbx1 ^@ http://purl.uniprot.org/uniprot/B9EII4|||http://purl.uniprot.org/uniprot/F6ZP09|||http://purl.uniprot.org/uniprot/P70323 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA as a dimer (By similarity). Interacts with DSCR6 (PubMed:21177346). Interacts with NKX2-5 (PubMed:16556915).|||Expressed in skeletal muscle, lung and testis (PubMed:11412027). Highly expressed in hair follicle stem cell, but not in terminally differentiating cells (PubMed:22495305).|||In the developing embryo, first expressed in the mesoderm at day 7.5. Expressed in the pharyngeal endoderm and the mesodermal cores of the pharyngeal arches at 8.5 dpc. At day 9.5, primarily expressed in the head region, specifically the mesenchyme and epithelium of the pharyngeal region and the otic vesicle epithelium. By day 12.5, expression is still observed in the latter as well as in the tongue mesenchyme, tooth buds and branching lung epithelium.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice die at birth with hypoplastic and intermittent missing craniofacial muscles, cleft palate, absent thymus and parathyroid glands, as well as a persistent truncus arteriosus (PTA) with a ventricular septal defect (VSD) (PubMed:11242049, PubMed:11239417, PubMed:11242110, PubMed:15385444). The first arch forms in but the distal pharyngeal arch fails to become segmented, thereby explaining, why the pharyngeal arch derived structures are malformed (PubMed:11242049, PubMed:11239417, PubMed:11242110). Conditional deletion in the skin epithelium leads to delayed tissue regeneration due to progressive depletion of stem cells (PubMed:22495305).|||Nucleus|||Transcription factor that plays a key role in cardiovascular development by promoting pharyngeal arch segmentation during embryonic development (PubMed:11412027, PubMed:11242049, PubMed:11239417, PubMed:11242110, PubMed:15703190, PubMed:16556915). Also involved in craniofacial muscle development (PubMed:15385444). Together with NKX2-5, acts as a regulator of asymmetric cardiac morphogenesis by promoting expression of PITX2 (PubMed:16556915). Acts upstream of TBX1 for the formation of the thymus and parathyroid glands from the third pharyngeal pouch (PubMed:31412026). Required for hair follicle stem cell self-renewal (PubMed:22495305). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence (By similarity). http://togogenome.org/gene/10090:Cyp2c55 ^@ http://purl.uniprot.org/uniprot/Q9D816 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highest level in colon. Low levels in liver and small intestine.|||Metabolizes arachidonic acid mainly to 19-hydroxyeicosatetraenoic acid (HETE).|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Sclt1 ^@ http://purl.uniprot.org/uniprot/G5E861 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that links SCN10A to clathrin. Regulates SCN10A channel activity, possibly by promoting channel internalization (By similarity).|||Interacts with SCN10A and clathrin. Identified in a complex containing SCN10A, clathrin and SCLT1 (By similarity).|||centriole http://togogenome.org/gene/10090:Zfp830 ^@ http://purl.uniprot.org/uniprot/Q8R1N0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE; this complex binds preferentially to RNA. Interacts with XAB2. Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex. The IB complex does not contain PRPF19.|||Expressed in preimplantation embryos.|||May play a role in pre-mRNA splicing as component of the spliceosome (By similarity). Acts as an important regulator of the cell cycle that participates in the maintenance of genome integrity (PubMed:21191184, PubMed:23213458, PubMed:25168238, PubMed:15988037). During cell cycle progression in embryonic fibroblast, prevents replication fork collapse, double-strand break formation and cell cycle checkpoint activation (PubMed:21191184). Controls mitotic cell cycle progression and cell survival in rapidly proliferating intestinal epithelium and embryonic stem cells (PubMed:23213458). During the embryo preimplantation, controls different aspects of M phase (PubMed:15988037). During early oocyte growth, plays a role in oocyte survival by preventing chromosomal breaks formation, activation of TP63 and reduction of transcription (PubMed:25168238).|||Mice die by the end of preimplantation development and exhibit a dramatic reduction in the total cell number, a high mitotic index, and the presence of abnormal mitotic figures. Mice appear unwell with significant loss of body weight and rapidly decline afterwards and die. Mice reveal major alterations of their digestive tract including a distended and filled stomach and an intestine lacking spontaneous peristaltism. The small intestine exhibits a thinner wall, less abundant and stunted villi and highly disorganized crypts. Large portion of the gut are almost devoid of normal epithelial structure (PubMed:23213458). Conditional inactivation of Omcg1 in oocytes leads to sterility and early folliculogenesis arrest (PubMed:25168238).|||Nucleus|||Nucleus speckle|||Phosphorylated in response to DNA damage by the cell cycle checkpoint kinases ATR/ATM.|||Widely expressed at low level. Expressed in oocytes from primordial to antral follicles. Also detected in somatic cells of the ovary, namely, in granulosa cells from the pre-antral follicle stage onward (PubMed:25168238). http://togogenome.org/gene/10090:Dhx33 ^@ http://purl.uniprot.org/uniprot/Q80VY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Cytoplasm|||Implicated in nucleolar organization, ribosome biogenesis, protein synthesis and cytoplasmic dsRNA sensing (By similarity) (PubMed:21930779). Stimulates RNA polymerase I transcription of the 47S precursor rRNA. Associates with ribosomal DNA (rDNA) loci where it is involved in POLR1A recruitment (PubMed:21930779). In the cytoplasm, promotes elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation (PubMed:26100019). Senses cytosolic dsRNA mediating NLRP3 inflammasome formation in macrophages and type I interferon production in myeloid dendritic cells (By similarity). Required for NLRP3 activation induced by viral dsRNA and bacterial RNA (By similarity). In dendritic cells, required for induction of type I interferon production induced by cytoplasmic dsRNA via the activation of MAPK and NF-kappa-B signaling pathways (PubMed:24037184).|||Inflammasome|||Interacts with UBTF (PubMed:21930779). Interacts with DDX3X, EIF3G and EIF3H; the interaction is independent of RNA (PubMed:26100019). Interacts (via HA2 region and Helicase C-terminal domain) with the components of the large ribosomal subunit RPL3, RPL7, RPL26 and RPL27 (PubMed:26100019). Binds to mRNA (PubMed:26100019). Interacts (via the helicase C-terminal domain) with MAVS (PubMed:24037184). Binds to double-stranded RNA (via the helicase C-terminal domain) (PubMed:24037184).|||Nucleus|||Ubiquitinated, leading to its degradation by the proteasome (PubMed:29273634). Deubiquitinated by USP36 (PubMed:29273634).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Tmprss11a ^@ http://purl.uniprot.org/uniprot/Q3UQ41 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Membrane|||Probable serine protease which may play a role in cellular senescence. Overexpression inhibits cell growth and induce G1 cell cycle arrest. http://togogenome.org/gene/10090:Ctla2b ^@ http://purl.uniprot.org/uniprot/P12400 ^@ Function|||Similarity ^@ Not known, expressed in activated T-cell.|||To the propeptide regions of cysteine proteases. http://togogenome.org/gene/10090:Mest ^@ http://purl.uniprot.org/uniprot/Q07646 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily.|||Endoplasmic reticulum membrane|||Expressed in mesodermal tissues. Isoform 1 is exclusively expressed from the paternal allele in all fetal tissues and cell lines examined, whereas isoform 2 is preferentially expressed from the paternal allele in a tissue-type-specific manner.|||Expressed in the nascent mesoderm of gastrulating embryos. At 7.0 dpc expression detected in both the intraembryonic mesoderm and the extraembryonic mesoderm cells of the amniotic fold. At 8.5 dpc expressed predominantly in the head mesenchyme, allantois, and the mesodermal layer of the amnion, chorion and yolk. In 9.5 dpc embryos highly expressed in the mesenchymal tissues, presomitic paraxial mesoderm, heart and branchial arches. http://togogenome.org/gene/10090:Tctn3 ^@ http://purl.uniprot.org/uniprot/Q8R2Q6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tectonic family.|||Membrane|||Part of the tectonic-like complex (also named B9 complex).|||Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. May be involved in apoptosis regulation (By similarity). Necessary for signal transduction through the sonic hedgehog (Shh) signaling pathway. http://togogenome.org/gene/10090:Prps1l3 ^@ http://purl.uniprot.org/uniprot/G3UXL2|||http://purl.uniprot.org/uniprot/Q3UYQ0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ribose-phosphate pyrophosphokinase family.|||Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.|||Homodimer. The active form is probably a hexamer composed of 3 homodimers. http://togogenome.org/gene/10090:Zfp11 ^@ http://purl.uniprot.org/uniprot/P10751 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Cbln4 ^@ http://purl.uniprot.org/uniprot/Q8BME9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a synaptic organizer in specific subsets of neurons in the brain (PubMed:29691328). Essential for the formation and maintenance of inhibitory GABAergic synapses (PubMed:25534236). Promotes the development of dendrite-targeting inhibitory GABAergic synapses made by somatostatin-positive interneurons (PubMed:30679375). May contribute to the function of ventral medial habenula region of the brain implicated in the regulation of anxiety-related behaviors (PubMed:30287486). May play a role in CBLN3 export from the endoplasmic reticulum and secretion (PubMed:17030622).|||Expressed in brain with high levels in particular thalamic nuclei. In the thalamus, predominantly expressed in neurons within the parafascicular nucleus. Found in the hippocampus, mostly in the dendrites and somata of pyramidal neurons (at protein level). Very low or no expression in most other brain regions. Highly expressed in the ventral medial habenula.|||Homohexamer; disulfide-linked homotrimers. The trimers are assembled via the globular C1q domains. The trimers associate via N-terminal cysteine residues to form disulfide-linked hexamers (By similarity). May form oligomers with CBLN1, CBLN2 and CBLN3 prior to secretion (PubMed:17030622, PubMed:29782851). Once secreted, does not interact with other CBLN family members (PubMed:17030622). Strongly interacts with DCC in a NTN1-displaceable fashion (PubMed:22220752, PubMed:29782851). Weakly binds to NRXN1 and NRXN2 long and short isoforms produced by alternative promoter usage (PubMed:22220752, PubMed:29782851). Interaction with NRXN3 short isoform is hardly detectable; no interaction at all with NRXN3 long isoform (PubMed:22220752, PubMed:29782851). Does not interact with NEO1, GRID1 and GRID2 (PubMed:22220752, PubMed:29782851).|||In the developing brain, expressed as early as 10-13 dpc. Expression level peaks at 18 dpc and gradually decreases afterwards. Expressed in developing somatostatin-positive basket cells.|||Mutant animals are fertile, have normal life spans and have no overt anatomical abnormalities (PubMed:22220752). They have a normal corpus callosum, hippocampal commisure and pontine nucleus and no other gross neuroanatomical abnormalities (PubMed:22220752). Mice exhibit increased anxiety-related behavior (PubMed:30287486). Triple CBLN1, CBLN2 and CBLN4 knockout mice exhibit impairments in sensory processing and sensorimotor gating, in addition to severe motor deficits, seizures and reduced synapse density in the hippocampus of aging mice (PubMed:29691328).|||Secreted|||Sialoglycoprotein.|||Synapse http://togogenome.org/gene/10090:Hoxb2 ^@ http://purl.uniprot.org/uniprot/P0C1T1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 8 dpc, expressed in the developing hindbrain in regions that give rise to rhombomeric segmentations r3, r4 and r5.|||Belongs to the Antp homeobox family. Proboscipedia subfamily.|||Nucleus|||Part of the nuclear protein complex gamma-globin promoter and enhancer binding factor (gamma-PE) composed at least by SATB1 and HOXB2.|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Vmn2r39 ^@ http://purl.uniprot.org/uniprot/L7N2E5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Hyal4 ^@ http://purl.uniprot.org/uniprot/L0MX76|||http://purl.uniprot.org/uniprot/Q05A56 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 56 family.|||Endo-hyaluronidase that degrades hyaluronan to smaller oligosaccharide fragments. Has also chondroitin sulfate hydrolase activity, The best substrate being the galactosaminidic linkage in the sequence of a trisulfated tetrasaccharide (By similarity).|||Membrane http://togogenome.org/gene/10090:Napg ^@ http://purl.uniprot.org/uniprot/Q9CWZ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the heart, liver and kidneys with lower expression in the brain, spleen, lung, muscle and testes.|||Belongs to the SNAP family.|||Golgi apparatus|||Interacts with RAB11FIP5 (By similarity). Interacts with VTI1A (PubMed:9705316).|||Membrane|||Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus. http://togogenome.org/gene/10090:Ctrb1 ^@ http://purl.uniprot.org/uniprot/Q9CR35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||extracellular space http://togogenome.org/gene/10090:Hk1 ^@ http://purl.uniprot.org/uniprot/G3UVV4|||http://purl.uniprot.org/uniprot/P17710|||http://purl.uniprot.org/uniprot/Q3TTB4|||http://purl.uniprot.org/uniprot/Q6GQU1 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hexokinase family.|||Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively). Does not phosphorylate N-acetyl-D-glucosamine (By similarity). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity). Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan. When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331).|||Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate. Hexokinase activity is inhibited by N-acetyl-D-glucosamine.|||In rapidly growing tumor cells exhibiting high glucose catabolic rates, isoform HK1 is markedly elevated. Isoform HK1-SA, isoform HK1-SB and isoform HK1-SC are found only in spermatogenic cells. Isoform HK1-SC is detected in round spermatids, condensing spermatids and mature sperm where it is found in the head membranes, mitochondria of the midpiece and the fibrous sheath of the flagellum. Expressed within the principal piece and midpiece of sperm tail (at protein level).|||Isoform HK1-SA: First expressed during meiosis and continues to be present in postmeiotic germ cells (PubMed:8396993, PubMed:9450953). Isoform HK1-SB: Present only in postmeiotic germ cells (PubMed:8396993).|||Membrane|||Mitochondrion outer membrane|||Monomer (By similarity). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941). Interacts with VDAC1. The HK1-VDAC1 complex interacts with ATF2 (By similarity). Interacts (via N-terminal spermatogenic cell-specific region) with PFKM isoform 2 and isoform 3 (via C-terminus) (PubMed:19889946). Interacts with SMAD5 (By similarity).|||Produced by alternative initiation at Met-53 of isoform HK1-SA.|||Produced by alternative splicing and alternative initiation at Met-53 of isoform HK1-SA.|||The N- and C-terminal halves of this hexokinase contain a hexokinase domain. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule.|||Tyrosine-phosphorylated.|||cytosol http://togogenome.org/gene/10090:Dnm3 ^@ http://purl.uniprot.org/uniprot/Q8BZ98 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.|||Cytoplasm|||Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes, in particular endocytosis (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Slc6a9 ^@ http://purl.uniprot.org/uniprot/P28571 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A9 subfamily.|||Cell membrane|||Expressed in the brain (at protein level) (PubMed:27773429). At 11 dpc, expressed in the ventral part of the ventricular zone. At 15 dpc, also expressed in adjacent mantle tissue and the meninges. Strongly expressed in 12 dpc and 15 dpc liver.|||Expressed in the brain.|||Expression is present at low levels as early as 9 dpc and 10 dpc, but strongly increases at 13 dpc and remains at high levels up to 15 dpc. Also expressed in adult.|||Interacts with EXOC1; interaction increases the transporter capacity of SLC6A9 probably by promoting its insertion into the cell membrane (By similarity). Interacts with EXOC3 and EXOC4 (By similarity).|||Mice show severe motor and respiration deficits at birth and die during the first postnatal day (PubMed:14622582). Accumulation of glycine in the synaptic cleft results in over-activation of postsynaptic glycine receptors and death of the newborn animals due to respiratory and feeding problem (PubMed:14622582).|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform GlyT-1C.|||Sodium- and chloride-dependent glycine transporter which is essential for regulating glycine concentrations at inhibitory glycinergic synapses.|||Sodium- and chloride-dependent glycine transporter. http://togogenome.org/gene/10090:Cd70 ^@ http://purl.uniprot.org/uniprot/O55237|||http://purl.uniprot.org/uniprot/Q05A52 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor family.|||By IL-2 and concanavalin A (Con A).|||Cytokine which is the ligand for CD27. The CD70-CD27 pathway plays an important role in the generation and maintenance of T cell immunity, in particular during antiviral responses. Upon CD27 binding, induces the proliferation of costimulated T-cells and enhances the generation of cytolytic T-cells.|||Homotrimer.|||Membrane|||N-glycosylated.|||Very low level of expression. Detected in splenocytes and thymocytes. http://togogenome.org/gene/10090:Ncam1 ^@ http://purl.uniprot.org/uniprot/P13595 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with MDK. Found in a complex with SLC39A6, SLC39A10 and with NCAM1; this complex controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-tomesenchymal transition (PubMed:28098160).|||This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. http://togogenome.org/gene/10090:Adi1 ^@ http://purl.uniprot.org/uniprot/Q99JT9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acireductone dioxygenase (ARD) family.|||Binds either 1 Fe or Ni cation per monomer (PubMed:26858196). Iron-binding promotes an acireductone dioxygenase reaction producing 2-keto-4-methylthiobutyrate, while nickel-binding promotes an acireductone dioxygenase reaction producing 3-(methylsulfanyl)propanoate (PubMed:26858196).|||Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site (PubMed:26858196). Fe-containing acireductone dioxygenase (Fe-ARD) produces formate and 2-keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of methionine in the methionine recycle pathway (PubMed:26858196). Ni-containing acireductone dioxygenase (Ni-ARD) produces methylthiopropionate, carbon monoxide and formate, and does not lie on the methionine recycle pathway (PubMed:26858196). Also down-regulates cell migration mediated by MMP14 (By similarity).|||Cell membrane|||Cytoplasm|||Monomer. Interacts with MMP14.|||Nucleus http://togogenome.org/gene/10090:Or10aa1 ^@ http://purl.uniprot.org/uniprot/Q3U4A2|||http://purl.uniprot.org/uniprot/Q7TRV9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp2b13 ^@ http://purl.uniprot.org/uniprot/A6H6J2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Commd9 ^@ http://purl.uniprot.org/uniprot/Q8K2Q0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle|||Interacts with RELB and NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL1.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits.|||Nucleus http://togogenome.org/gene/10090:Bola3 ^@ http://purl.uniprot.org/uniprot/Q14A77|||http://purl.uniprot.org/uniprot/Q8CEI1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins. Probably acts together with NFU1.|||Belongs to the BolA/IbaG family.|||Interacts with NFU1.|||Mitochondrion http://togogenome.org/gene/10090:Or5p81 ^@ http://purl.uniprot.org/uniprot/Q8VEW6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Notum ^@ http://purl.uniprot.org/uniprot/Q8R116 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the pectinacetylesterase family. Notum subfamily.|||Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors.|||Secreted|||The molecular function of NOTUM has remained unclear for many years. It was initially thought to hydrolyze glycosaminoglycan (GAG) chains of glypicans, thereby affecting glypicans ability to interact with Wnt ligands. It was later reported to trigger glypican shedding, by mediating cleavage of their GPI-anchor (PubMed:17967162). However, while NOTUM specifically inhibit the Wnt signaling pathway, more pleiotropic effects would be expected from an enzyme affecting glypicans. It was finally shown that it requires glypicans to suppress Wnt signaling, but does not cleave their GPI-anchor. It acts by mediating depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled receptors.|||Widely expressed. Expressed in lung, ovary, kidney, liver and brain. Not detected in thymus, heart, spleen, stomach, skeletal muscle and bone marrow. http://togogenome.org/gene/10090:Rnf145 ^@ http://purl.uniprot.org/uniprot/Q5SWK7 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By high-cholesterol diet.|||E3 ubiquitin ligase that catalyzes the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. In response to bacterial infection, negatively regulates the phagocyte oxidative burst by controlling the turnover of the NADPH oxidase complex subunits. Promotes monoubiquitination of CYBA and 'Lys-48'-linked polyubiquitination and degradation of CYBB NADPH oxidase catalytic subunits, both essential for the generation of antimicrobial reactive oxygen species (PubMed:26194095). Involved in the maintenance of cholesterol homeostasis. In response to high sterol concentrations ubiquitinates HMGCR, a rate-limiting enzyme in cholesterol biosynthesis, and targets it for degradation. The interaction with INSIG1 is required for this function (PubMed:29374057). In addition, triggers ubiquitination of SCAP, likely inhibiting its transport to the Golgi apparatus and the subsequent processing/maturation of SREBPF2, ultimately down-regulating cholesterol biosynthesis (PubMed:29068315).|||Endoplasmic reticulum membrane|||Interacts (via YLYF motif) with INSIG1 and INSIG2.|||Knockout mice generated by CRISPR-Cas9-mediated gene editing are born at the expected Mendelian rate. Compared to wild-type littermates, mutant mice show slightly reduced body weight and increased serum cholesterol levels. http://togogenome.org/gene/10090:Or4d10c ^@ http://purl.uniprot.org/uniprot/Q8VG74 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krt73 ^@ http://purl.uniprot.org/uniprot/Q6NXH9 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (By similarity).|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Gli1 ^@ http://purl.uniprot.org/uniprot/P47806 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-520 down-regulates transcriptional activity. Deacetylated by HDAC1.|||Acts as a transcriptional activator. Binds to the DNA consensus sequence 5'-GACCACCCA-3'. Regulates the transcription of specific genes during normal development. Plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling. Plays a role in cell proliferation and differentiation via its role in SHH signaling.|||Belongs to the GLI C2H2-type zinc-finger protein family.|||Cytoplasm|||Interacts with KIF7 (PubMed:19592253). Interacts with STK36. Interacts with ZIC1; the interaction enhances transcription activation. Interacts with SUFU; this inhibits transcriptional activation by GLI1 (By similarity).|||Is detected on days 10 through 18 of embryonic development. During gestation it is detected in meckels precartilage mesenchyme, the basis occipitus, rib mesenchymal condensations, primordial vertebral bodies, digital mesenchymal condensations in forefoot and hindfoot plates, the ependymal layer of the spinal cord, and the mesoderm of the gastrointestinal tract. Expression persists throughout gestation in developing bone and cartilage of the extremities, the ribs, and the vertebral bodies as well as the gastrointestinal tract mesoderm.|||Nucleus|||Phosphorylated in vitro by ULK3.|||Ubiquitinated by the CRL2(FEM1B) complex, suppressing GLI1 transcriptional activator activity. http://togogenome.org/gene/10090:Or2j3 ^@ http://purl.uniprot.org/uniprot/Q8VFC2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Saxo1 ^@ http://purl.uniprot.org/uniprot/B1AXP3 ^@ Similarity ^@ Belongs to the FAM154 family. http://togogenome.org/gene/10090:Krt20 ^@ http://purl.uniprot.org/uniprot/Q9D312 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed at low levels in the more differentiated suprabasal regions of the small intestine, and at higher levels in the colon, mainly in the upper region and in scattered cells throughout the remaining epithelium. Also expressed in epithelial cells of bladder, ileum and stomach and at lower levels in pancreas and earskin. The phosphorylated form is nearly exclusively expressed in goblet cells of the small intestine and in the lumen-proximal cells of the colon (at protein level). Also expressed in jejunum and duodenum.|||Heterotetramer of two type I and two type II keratins. Associates with KRT8.|||Hyperphosphorylation at Ser-13 occurs during the early stages of apoptosis but becomes less prominent during the later stages (By similarity). Phosphorylation at Ser-13 also increases in response to stress brought on by cell injury.|||Plays a significant role in maintaining keratin filament organization in intestinal epithelia. When phosphorylated, plays a role in the secretion of mucin in the small intestine.|||Proteolytically cleaved by caspases during apoptosis. Cleavage occurs at Asp-235 (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Crlf1 ^@ http://purl.uniprot.org/uniprot/Q9JM58 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 3 subfamily.|||Forms covalent di- and tetramers. Forms a heteromeric complex with cardiotrophin-like cytokine CLCF1/CLC; the CRLF1-CLCF1 complex is a ligand for the ciliary neurotrophic factor receptor/CNTFR. The CRLF1-CLCF1 heterodimer, as well as tripartite signaling complex formed by CRLF1, CLCF1 and CNTFR bind SORL1 (via N-terminal ectodomain); within this complex, the interaction is mediated predominantly by the CRLF1 moiety.|||In complex with CLCF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development (By similarity). Plays a role in the initiation and/or maintenance of suckling in neonatal mice (PubMed:10359701). May also play a regulatory role in the immune system (By similarity).|||Secreted|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||Widely expressed in the embryo. Not detected in the brain of adult mice. http://togogenome.org/gene/10090:Ifi207 ^@ http://purl.uniprot.org/uniprot/E9Q3L4|||http://purl.uniprot.org/uniprot/Q8BW36 ^@ Similarity ^@ Belongs to the HIN-200 family. http://togogenome.org/gene/10090:Pms1 ^@ http://purl.uniprot.org/uniprot/Q8K119 ^@ Similarity ^@ Belongs to the DNA mismatch repair MutL/HexB family. http://togogenome.org/gene/10090:Arl2bp ^@ http://purl.uniprot.org/uniprot/Q9D385 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ARL2BP family.|||Cytoplasm|||Interacts with GTP bound ARL2 and ARL3; the complex ARL2-ARL2BP as well as ARL2BP alone, binds to SLC25A4/ANT1. Interaction with ARL2 may be required for targeting to cilia basal body (By similarity). Interacts with STAT3; interaction is enhanced with ARL2. Found in a complex with ARL2BP, ARL2 and SLC25A6 (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4. Interacts with STAT2, STAT3 and STAT4.|||Mitochondrion intermembrane space|||Nucleus|||Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2 (By similarity).|||Widely expressed, with most abundant activity in brain, especially in hippocampus and cortex. Also expressed in lung, cerebellum, liver, kidney, retina, spleen, muscle and heart (at protein level).|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Serinc2 ^@ http://purl.uniprot.org/uniprot/B2KFY0|||http://purl.uniprot.org/uniprot/E9Q7Q6|||http://purl.uniprot.org/uniprot/Q8C6D8|||http://purl.uniprot.org/uniprot/Q8K0E7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TDE1 family.|||Membrane http://togogenome.org/gene/10090:Mrps26 ^@ http://purl.uniprot.org/uniprot/Q80ZS3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS26 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Prkdc ^@ http://purl.uniprot.org/uniprot/P97313 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity seems to be attenuated by autophosphorylation. Binding to the SL1 region of U3 small nucleolar RNA promotes auto-phosphorylation activity. Inhibited by wortmannin.|||Autophosphorylated at two clusters, the T2609 cluster and the S2056 cluster (PubMed:24158435, PubMed:32103174). Autophosphorylated on Ser-2053, Thr-2605, Thr-2634 and Thr-2643. Ser-2053 and Thr-2605 are DNA damage-inducible phosphorylation sites (inducible with ionizing radiation, IR) dephosphorylated by PPP5C (PubMed:24158435, PubMed:32103174). Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair (By similarity). Autophosphorylation in trans within DNA-PK complexes loaded on DNA ends leads to the dissociation of PRKDC from DNA and the transition into the short-range NHEJ complex (By similarity). Autophosphorylation of the T2609 cluster is required for hematopoietic development and protein synthesis in erythrocytes precursors (PubMed:32103174).|||Belongs to the PI3/PI4-kinase family.|||DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86). Formation of this complex may be promoted by interaction with ILF3. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA. Interacts with DNA-PKcs-interacting protein (KIP) with the region upstream the kinase domain. PRKDC alone also interacts with and phosphorylates DCLRE1C, thereby activating the latent endonuclease activity of this protein. Interacts with C1D. Interacts with TTI1 and TELO2. Interacts with CIB1. Interacts with SETX. Interacts with NR4A3; the DNA-dependent protein kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents NR4A3 ubiquitination and degradation. Interacts with BRAT1. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA. Interacts with KAT5.|||Defects in Prkdc are the cause of severe combined immune deficiency (SCID) which is characterized by a lack of mature functional lymphocytes and a high susceptibility to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency syndrome in human infants.|||Nucleus|||Polyubiquitinated by RNF144A, leading to proteasomal degradation.|||S-nitrosylated by GAPDH.|||Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (By similarity). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (By similarity). Must be bound to DNA to express its catalytic properties (By similarity). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (By similarity). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (By similarity). Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (By similarity). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (By similarity). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (PubMed:12426399). Also involved in modulation of transcription (By similarity). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (By similarity). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (By similarity). Recognizes the substrate consensus sequence [ST]-Q (By similarity). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (By similarity). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (By similarity). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (By similarity). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (By similarity). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (PubMed:24158435). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (By similarity). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (By similarity). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (By similarity).|||Viable. Normal number of erythrocytes and platelets. Normal translation levels in erythrocyte precursors.|||nucleolus http://togogenome.org/gene/10090:Vps29 ^@ http://purl.uniprot.org/uniprot/Q9QZ88 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (By similarity). Acts also as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). In the endosomes, retriever complex drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling. The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with ANKRD27 (By similarity). Has no activity towards p-nitrophenylphosphate, p-nitrophenylphosphorylcholine or phosphatidylinositlphosphates or a phosphorylated peptide derived from retromer cargo (in vitro) (PubMed:21629666, PubMed:15965486).|||Belongs to the VPS29 family.|||Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS) formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:21040701, PubMed:20875039, PubMed:21920005). The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (By similarity). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described retromer complex (also called SNX-BAR retromer) is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (By similarity). Component of the heterotrimeric retriever complex formed by VPS26C, VPS29 and VPS35L (By similarity). Interacts with VPS35L (By similarity). Interacts with VPS26A, VPS26B, VPS35, ANKRD27 (PubMed:20875039, PubMed:21920005, PubMed:24856514). Interacts with SNX1, SNX2, SNX27, WASHC5 (By similarity).|||Cytoplasm|||Endosome membrane|||Membrane|||Was originally believed to be a metal-dependent phosphatase but shown to lack catalytic activity; can bind metals (Zn(2+) and Mn(2+)) with very low affinity suggesting that metal binding is not required for its function. http://togogenome.org/gene/10090:Vmn1r155 ^@ http://purl.uniprot.org/uniprot/D3YTY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Git1 ^@ http://purl.uniprot.org/uniprot/Q68FF6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in the brain (at protein level) (PubMed:15182672, PubMed:16959763, PubMed:17310244, PubMed:19273721, PubMed:19383529, PubMed:21499268, PubMed:24297929). Also expressed at high levels in lung and heart (PubMed:19273721). In lung, expressed in endothelial cells, especially in capillaries; also expressed in smooth muscle and epithelial cells of bronchi (at protein level) (PubMed:19273721). Expressed in bone marrow mesenchymal stem cells, as well as in osteoclasts and bone marrow-derived macrophages (at protein level) (PubMed:25138700, PubMed:32460388).|||Forms homodimers and possibly oligomers (By similarity). May forms heterooligomers with GIT2 (By similarity). Interacts with G protein-coupled receptor kinases, including GRK2, GRK3, GRK5 and GRK6 (By similarity). Interacts with PPFIA1, PPFIA2 and PPFIA4 (By similarity). Interacts with GRIP1 and forms a ternary complex with PPFIA1 and GRIP1 (By similarity). Directly interacts with ARHGEF7/beta-PIX, forming in vitro a heptameric complex made of a GIT1 dimer and an ARHGEF7 trimer (By similarity). Directly interacts with PXN/paxillin; this interaction is enhanced in the presence of ARHGEF7 (By similarity). Directly interacts (via C-terminus) with TGFB1I1/Hic-5 (via LD motif 3) (PubMed:12153727). Directly interacts with PTK2/FAK1 (By similarity). May interact with PTK2B/PYK2; this interaction may be indirect (By similarity). Interacts with AMPA receptors GRIA2/3 (By similarity). Directly interacts with protein Piccolo/PCLO (By similarity). Forms a complex with Ephrin-B1/EFNB1 and NCK2/GRB4 (via SH2); this interaction is important for spine morphogenesis and synapse formation. Interaction with NCK2 is transient and depends upon GIT1 phosphorylation at Tyr-392 (PubMed:17310244). Interacts with GRIN3A/GluN3A (via C-terminus); this interaction competes with GIT1 interaction with ARHGEF7 and limits synaptic localization of GIT1 (PubMed:24297929). Interacts with IKBKG/NEMO in resting bone mesenchymal stem cells, as well as in TNF-stimulated cells; this interaction may increase IKBKG affinity for 'Lys-63'-linked polyubiquitin chains (By similarity). Interacts with GABA(A) receptors, including GABRB3 and GABRG2 (By similarity). Interacts with SCRIB (PubMed:15182672). Interacts (via N- and C-terminus) with ENTR1/SDCCAG3 (via N-terminus); this interaction is direct (PubMed:23108400). May form a tripartite complex with ENTR1 and PTPN13 (By similarity). Interacts with YWHAZ (PubMed:16959763). Interacts with PAK1 (By similarity). Interacts with PAK3 (By similarity). Directly interacts (via N-terminus) with gamma-tubulin (By similarity). Interacts with MAPK1 and MAPK3; this interaction is required for MAPK1/3 recruitment to focal adhesions (PubMed:15923189).|||GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase. Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (By similarity). May promote cell motility both by regulating focal complex dynamics and by the activation of RAC1 (By similarity). May act as scaffold for MAPK1/3 signal transduction, recruiting MAPK1/3 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (By similarity). Plays a role in brain development and function (PubMed:25792865, PubMed:33010377). Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (PubMed:20043896, PubMed:29554125). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (By similarity). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (PubMed:21499268). Required for successful bone regeneration during fracture healing (PubMed:25138700, PubMed:24586541, PubMed:32460388). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (PubMed:32460388). May play a role in angiogenesis during fracture healing (PubMed:24586541, PubMed:31502302). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (By similarity). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721).|||In lung, up-regulated from postnatal day 3 (P3). Expression levels decrease after P5 and at P25, they are similar to those observed at P0 (PubMed:19273721). During the fracture healing process, expression is strongly up-regulated in the healing callus 14 days after the lesion and remains highly expressed at day 21 (PubMed:24586541).|||Knockout mice are born at the expected Mendelian ratio, but have decreased survival compared to wild-type littermates, with about 50% of mutant mice dying postnatally. Surviving animals develop normally and are fertile (PubMed:19273721, PubMed:19383529, PubMed:21499268, PubMed:33010377). They are however 60-70% smaller than wild-type littermates (PubMed:21499268). A major abnormality in knockout mice is impaired lung development, characterized by markedly reduced numbers of pulmonary blood vessels and increased alveolar spaces (PubMed:19273721). Although knockout mice show an unaltered brain gross morphology and neuronal density, they display microcephaly, with an overall brain size about 32% smaller compared to wild-type controls. This phenotype may be due to smaller neuronal size, rather than reduced neuron number, compared to wild-type littermates (PubMed:20043896, PubMed:25792865, PubMed:33010377). Mutant mice exhibit reduced dendritic length and spine density in the hippocampus and the cortex, which may lead to poor adaptation to new environments and impaired fear response (PubMed:19383529, PubMed:20043896, PubMed:25792865, PubMed:29554125). This effect on the brain is not uniform. Multiple brain regions suffer local atrophy, including extensive areas of the cortex, thalamus, and hippocampus, white matter tracts have a reduced volume, most notably in the anterior commissure, but also in the cerebral peduncle, fornix, and spinal trigeminal tract. On the other hand, local hypertrophy is detected in the basal ganglia, the accumbens, caudate putamen, and amygdala, as well as in the cortical layer IV, and cerebellum (PubMed:33010377). The analysis of a genetrap mouse strain lacking GIT1 showed phenotypic traits similar to attention deficit-hyperactivity disorder (ADHD), including hyperactivity, impaired learning and memory, and enhanced theta rhythms. These phenotypic traits could be reversed by amphetamines and methylphenidate (PubMed:21499268, PubMed:26113791). Abnormal thalamic oscillations, cortical theta rhythms and behavioral hyperactivity were also normalized by ethosuximide (PubMed:26113791). The abnormal behaviors decreased with age (PubMed:21499268). ADHD phenotype and response to amphetamines were not seen in other knockout mouse models (PubMed:29554125). Mutant animals show altered gait (PubMed:25792865). They exhibit defects in motor coordination and motor learning in rotarod test and abnormal spatial learning and memory (PubMed:25792865, PubMed:29554125). Knockout mice exhibit delayed bone fracture healing process. They display a persistence of cartilagenous callus and decreased chondrocyte proliferation and apoptosis, leading to their accumulation in the fracture area (PubMed:25138700, PubMed:24586541). The healing callus exhibits reduced blood vessel volume and number, as well as a reduced osteoclast number (PubMed:24586541, PubMed:31502302).|||Phosphorylated on tyrosine residues by PTK2/FAK1 and SRC in growing fibroblasts. Phosphorylation at Tyr-392 is induced by activation of Ephrin-B1/EFNB1 and catalyzed by SRC family kinases. It is required for the interaction with NCK2 and for GIT1 recruitment to synapses in hippocampal neurons.|||Postsynapse|||Postsynaptic density|||Presynapse|||centrosome|||focal adhesion|||lamellipodium|||spindle pole http://togogenome.org/gene/10090:Nkx3-2 ^@ http://purl.uniprot.org/uniprot/P97503 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NK-3 homeobox family.|||During embryogenesis, expressed in a discrete domain within the mandibular component of the first branchial arch and later in the primordia of middle earassociated bones, the gonium and tympanic ring.|||Expressed widely in mesoderm at the gastroduodenal junction (at protein level). Expressed in visceral mesoderm and embryonic skeleton. Expression is restricted to immature proliferative chondrocytes during endochondral ossification.|||Nucleus|||Transcriptional repressor that acts as a negative regulator of chondrocyte maturation. PLays a role in distal stomach development; required for proper antral-pyloric morphogenesis and development of antral-type epithelium. In concert with GSC, defines the structural components of the middle ear; required for tympanic ring and gonium development and in the regulation of the width of the malleus. http://togogenome.org/gene/10090:Asb17 ^@ http://purl.uniprot.org/uniprot/Q8VHP9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Expressed in testis from 3 weeks of age onwards, reaching maximum levels by 4 to 5 weeks of age.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||Specifically expressed in testis (PubMed:15460110). Localizes to spermatogenic cells in testis, with highest expression in round spermatids and condensing spermatids and lower expression in pachytene spermatocytes (PubMed:15204681, PubMed:15460110).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Kcns1 ^@ http://purl.uniprot.org/uniprot/O35173|||http://purl.uniprot.org/uniprot/Q3TY49 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. S (TC 1.A.1.2) subfamily. Kv9.1/KCNS1 sub-subfamily.|||Cell membrane|||Detected in brain, but not in the other tissues tested. The highest levels of expression are in olfactory bulb, cerebral cortex, hippocampus, habenula, basolateral amygdaloid nuclei and cerebellum (PubMed:9305895).|||Heterotetramer with KCNB1 and KCNB2 (PubMed:9305895). Does not form homomultimers (PubMed:9305895).|||Membrane|||Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1 and KCNB2; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 and KCNB2 (PubMed:9305895).|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. http://togogenome.org/gene/10090:Tmco4 ^@ http://purl.uniprot.org/uniprot/Q91WU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMCO4 family.|||Membrane http://togogenome.org/gene/10090:H2al1h ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:Hmgb2 ^@ http://purl.uniprot.org/uniprot/P30681 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HMGB family.|||Both, HMG box 1 and HMG box 2, show antimicrobial activity.|||Chromosome|||Cytoplasm|||Interacts with POU2F2, POU2F1 and POU3F1 (PubMed:7720710). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (PubMed:9184213). Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Directly interacts with SET (By similarity). Interacts with LEF1 (PubMed:19805379).|||Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes. Binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (By similarity). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (PubMed:9184213). Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (PubMed:19890330). In the extracellular compartment acts as a chemokine. Promotes proliferation and migration of endothelial cells implicating AGER/RAGE (By similarity). Has antimicrobial activity in gastrointestinal epithelial tissues (By similarity). Involved in inflammatory response to antigenic stimulus coupled with pro-inflammatory activity (PubMed:25306442). May play a role in germ cell differentiation (PubMed:11262228). Involved in modulation of neurogenesis probably by regulation of neural stem proliferation (PubMed:24391977). Involved in articular cartilage surface maintenance implicating LEF1 and the Wnt/beta-catenin pathway (PubMed:19805379).|||Nucleus|||Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB2 (HMGB2C23hC45hC106h), 2- disulfide HMGB2 (HMGB2C23-C45C106h) and 3- sulfonyl HMGB2 (HMGB2C23soC45soC106so).|||Secreted|||Viable, with severe reduction of sperm production in males.|||Widely expressed in embryo. In adult mainly expressed in lymphoid organs and testes (PubMed:11262228). Expressed in primary spermatocytes. Expressed in the superficial zone of articular cartilage (PubMed:19805379). http://togogenome.org/gene/10090:Zcrb1 ^@ http://purl.uniprot.org/uniprot/Q9CZ96 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Interacts with ZRSR1 (PubMed:29617656).|||Expressed at higher level in heart and testis, and at lower level in cerebellum. Weakly expressed at low level in liver.|||nucleoplasm http://togogenome.org/gene/10090:Sh3glb1 ^@ http://purl.uniprot.org/uniprot/Q9JK48 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes.|||Belongs to the endophilin family.|||Cytoplasm|||Fibroblasts with a reduced level of Sh3glb1 show a defect in retrograde transport between the Golgi apparatus and the endoplasmic reticulum.|||Golgi apparatus membrane|||Homodimer, and heterodimer with SH3GLB2 (By similarity). Binds BAX; induction of apoptosis augments BAX binding (PubMed:16227588, PubMed:17381077). Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 (PubMed:12456676, PubMed:17086176). Interacts with UVRAG; UVRAG bridges the interaction to BECN1 indicative for an association with the PI3K complex II (PI3KC3-C2) (By similarity). Isoform 3 interacts with PPP1CC; this interaction leads to the inhibition of phosphatase activity (PubMed:17381077).|||Isoform 1 is widely expressed. Isoform 2 is brain-specific. Isoform 3 is predominantly expressed in testis, but it is also detected in liver and, at much lower levels, in skin, stomach and ovary.|||May be required for normal outer mitochondrial membrane dynamics. Required for coatomer-mediated retrograde transport in certain cells (PubMed:17086176). May recruit other proteins to membranes with high curvature. May promote membrane fusion (By similarity). Involved in activation of caspase-dependent apoptosis by promoting BAX/BAK1 activation (PubMed:16227588). Isoform 1 acts proapoptotic in fibroblasts (PubMed:24523556). Involved in caspase-independent apoptosis during nutrition starvation and involved in the regulation of autophagy. Activates lipid kinase activity of PIK3C3 during autophagy probably by associating with the PI3K complex II (PI3KC3-C2). Associated with PI3KC3-C2 during autophagy may regulate the trafficking of ATG9A from the Golgi complex to the peripheral cytoplasm for the formation of autophagosomes by inducing Golgi membrane tubulation and fragmentation. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2 (By similarity). Isoform 2 acts antiapoptotic in neuronal cells; involved in maintenance of mitochondrial morphology and promotes neuronal viability (PubMed:24523556).|||Midbody|||Mitochondrion outer membrane|||Phosphorylated at Thr-145 by CDK5; this phosphorylation is required for autophagy induction in starved neurons and facilitates homodimerization.|||The SH3 domain is required and sufficient for the interaction with UVRAG.|||Was originally thought to have lysophosphatidic acid acyltransferase activity, but by homology with SH3GL2/endophilin A1 is unlikely to have this activity.|||autophagosome membrane http://togogenome.org/gene/10090:Skor1 ^@ http://purl.uniprot.org/uniprot/D3YX64|||http://purl.uniprot.org/uniprot/Q8BX46 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SKI family.|||Expressed in brain with higher levels in embryo than adult. Expressed by migratory precursors of Purkinje cells in the postnatal brain. Also expressed in adult testis.|||Expressed in the developing cerebellum, pons, medulla oblongata and spinal cord. In embryonic brain, expressed in a subset of postmitotic neurons generated posterior to the midbrain-hindbrain border. In the developing spinal cord, selectively expressed in dorsal horn interneurons.|||Inhibits BMP signaling (By similarity). Acts as a transcriptional corepressor of LBX1.|||Interacts with SMAD1, SMAD2 and SMAD3 (By similarity). Interacts with LBX1.|||Nucleus http://togogenome.org/gene/10090:Pfn4 ^@ http://purl.uniprot.org/uniprot/Q9D6I3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the profilin family.|||Cytoplasm|||Expressed in testis, in germ cells in seminiferous tubules (at protein level).|||Homozygous knockout males are infertile, whereas females have normal fertility. Sperm from knockout mice display severe impairment in manchette formation, amorphous sperm head shape and flagellar defects, resulting in reduced sperm motility. Sperm of homozygous knockout males displays a significantly reduced acrosome reaction and decreased viability.|||Involved in male fertility (PubMed:35950913). Required for manchette development and acrosome biogenesis during spermiogenesis (PubMed:35950913). Binds in vitro to phospholipids, including phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), phosphatidylinositol 4-phosphate (PtdIns(4)P) and phosphatidic acid (PA). Contrary to other profilin family members, does not bind to actin in vitro (By similarity). http://togogenome.org/gene/10090:Hba-x ^@ http://purl.uniprot.org/uniprot/P06467|||http://purl.uniprot.org/uniprot/Q78PA4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the globin family.|||Heterotetramer of two zeta chains and beta-type chains.|||The zeta chain is an alpha-type chain of mammalian embryonic hemoglobin. http://togogenome.org/gene/10090:Stx18 ^@ http://purl.uniprot.org/uniprot/Q8VDS8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Component of a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L, and SEC22B. RINT1/TIP20L and ZW10 are associated with the complex through interaction with BNIP1/SEC20L. Interacts directly with USE1L and BNIP1/SEC20L (By similarity).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Syntaxin that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER. http://togogenome.org/gene/10090:Gdpd3 ^@ http://purl.uniprot.org/uniprot/Q99LY2 ^@ Activity Regulation|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Endoplasmic reticulum membrane|||Highly expressed in stomach and kidney. In stomach detected in the glandular epithelium. Predominantly expressed in the stomach (at protein level).|||Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines (PubMed:25528375, PubMed:27637550). Shows a preference for 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF), lysophosphatidylcholine (lyso-PC) and N-acylethanolamine lysophospholipids (PubMed:25528375). Does not display glycerophosphodiester phosphodiesterase activity, since it cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine (PubMed:25528375).|||Lysophospholipase D activity is stimulated by calcium. Loss of lysophospholipase D activity in presence of EDTA.|||Membrane|||perinuclear region http://togogenome.org/gene/10090:Prr5 ^@ http://purl.uniprot.org/uniprot/Q812A5 ^@ Caution|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PROTOR family.|||Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (By similarity). Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to MTOR and RICTOR within the TORC2 complex (By similarity). Interacts with MTOR.|||Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. PRR5 plays an important role in regulation of PDGFRB expression and in modulation of platelet-derived growth factor signaling. May act as a tumor suppressor in breast cancer (By similarity).|||Ubiquitously expressed. Expressed at high levels in kidney.|||Was originally thought to be the sequence of Arhgap8 but is actually the sequence of Prr5. http://togogenome.org/gene/10090:Magel2 ^@ http://purl.uniprot.org/uniprot/Q9QZ04 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Deficient mice show reduced embryonic viability, neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism, including increased fasting insulin and elevated cholesterol, in adulthood. Mutant mice also show abnormalities in the circadian pattern of feeding behavior. Deficient mice show features similar to those of Prader-Willi syndrome in humans.|||Early endosome|||Expressed predominantly in late development stages and adult brain.|||Nucleus|||Part of a complex consisting of MAGEL2, TRIM27 and USP7; directly interacts with USP7 (By similarity). Interacts with TRIM27. Interacts with VPS35; leading to recruitment at retromer-containing endosomes (By similarity). Interacts with BMAL1 and PER2.|||Probably enhances ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases, possibly through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. Acts as a regulator of retrograde transport via its interaction with VPS35. Recruited to retromer-containing endosomes and promotes the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1 together with TRIM27, leading to promote endosomal F-actin assembly (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Significantly promotes the cytoplasmic accumulation of CLOCK (PubMed:22208286). http://togogenome.org/gene/10090:Nyap1 ^@ http://purl.uniprot.org/uniprot/Q6PFX7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis.|||Belongs to the NYAP family.|||Expressed predominantly in brain where it is present in the neurons, but not in astrocytes or oligodendrites.|||Expression first detected in the cortical plate as early as 14 dpc, peaks in the middle neocortex at postnatal day 1 and then gradually decreases. At postnatal day 1, also expressed in the striatum, but not in the olfactory bulb.|||Interacts with ACOT9, ARHGAP26 and PIK3R2. Interacts with components of the WAVE1 complex, CYFIP1 and NCKAP1; this interaction mediates PI3K-WAVE1 association and actin cytoskeleton remodeling.|||Phosphorylated on tyrosine residues by FYN upon stimulation with CNTN5. Phosphorylation begins at 14 dpc, reaches a peak during perinatal days in brain, then gradually decreases.|||Triple knockout mice NYAP1/NYAP2/MYO16 are fertile and appear healthy. However, compared to wild-type mice they show a clear reduction in brain size, exhibiting a reduction in the size of the cortex and striatum, but not the olfactory bulb or corpus callosum. The total neurite length of neurons in these mice is also significantly shorter. http://togogenome.org/gene/10090:Lrrn3 ^@ http://purl.uniprot.org/uniprot/Q8CBC6 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the brain, in Stronger expression in the ventricular zone and anlage of thalamus, spinal cord, and dorsal root ganglion in 11-17 dpc cerebellum and cerebral cortex in adults.|||Membrane http://togogenome.org/gene/10090:Cstdc5 ^@ http://purl.uniprot.org/uniprot/Q497J0 ^@ Similarity ^@ Belongs to the cystatin family. http://togogenome.org/gene/10090:Or13c7d ^@ http://purl.uniprot.org/uniprot/Q9QZ19 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vat1l ^@ http://purl.uniprot.org/uniprot/Q80TB8 ^@ Similarity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily. http://togogenome.org/gene/10090:Med1 ^@ http://purl.uniprot.org/uniprot/Q925J9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mediator complex subunit 1 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Essential for embryogenesis, including development of the central nervous system, heart, liver and placenta and for erythropoiesis. Also required for normal transcriptional control of thyroid-stimulating hormone beta (TSHB) in the pituitary. Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. This subunit specifically interacts with a number of nuclear receptors in a ligand-dependent fashion including AR, ESR1, ESR2, PPARA, PPARG, RORA, RXRA, RXRG, THRA, THRB and VDR. Interacts with CTNNB1, GABPA, GLI3, PPARGC1A and TP53. Interacts with GATA1 and YWHAH. Interacts with CLOCK; this interaction requires the presence of THRAP3. Interacts with CCAR1 (By similarity). Interacts with NR4A3 (PubMed:12709428). Interacts (via IBM motif) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (By similarity).|||Nucleus|||Phosphorylated by MAPK1 or MAPK3 during G2/M phase which may enhance protein stability and promote entry into the nucleolus (By similarity). Phosphorylation increases its interaction with PSIP1 (By similarity).|||Widely expressed during embryonic development; at stages 9.5 dpc-10.5 dpc, expression is strongest in neural tissues. At 11.5 dpc-12.5 dpc, expression is abundant throughout embryonic tissues, being strongest in the developing liver, primitive gut, nasopharynx, and developing limb buds. Moderately expressed at this stage in the brain and optic stalk, branchial arch and urogential ridge. Expressed at a low level in the heart. By stage 13.5 dpc-14.5 dpc, expression is abundant in the forebrain, vagus nerve, dorsal root ganglia, nasopharynx, kidney, liver, pancreas, intestine, gut, thymus, lung, genital tubercle, tongue and lower jaw. Moderately expressed in the midbrain and expressed at a low level in the heart and large blood vessels. In the developing placenta, expression is moderate in the giant and spongiotrophoblast cell layers and strongest in the labyrinthine portion throughout 9.5 dpc-13.5 dpc.|||Widely expressed in the adult, with high levels of expression in the liver, lung, intestinal mucosa, kidney cortex, thymic cortex, splenic follicle and seminiferous epithelium in testis. Also expressed in the adult heart, brain, spleen and skeletal muscle. http://togogenome.org/gene/10090:Smg5 ^@ http://purl.uniprot.org/uniprot/Q6ZPY2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with TERT, PPP2CA and SMG1. Part of a complex that contains SMG1, SMG5, SMG7, PPP2CA, a short isoform of UPF3A (isoform UPF3AS, but not isoform UPF3AL) and phosphorylated UPF1. Not detected in complexes that contain unphosphorylated UPF1.|||Nucleus|||Plays a role in nonsense-mediated mRNA decay. Does not have RNase activity by itself. Promotes dephosphorylation of UPF1. Together with SMG7 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Necessary for TERT activity (By similarity). http://togogenome.org/gene/10090:Mab21l2 ^@ http://purl.uniprot.org/uniprot/Q8BPP1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mab-21 family.|||Cytoplasm|||Expressed in the adult cerebellum and eye, with lower levels in the adult forebrain (PubMed:10556287). In embryos at 10.5 days post-coitum strongly expressed in the rostral and distal regions of the developing neural retina, with no expression immediately adjacent to the closing optic fissure. Expression is also observed in the dorsal and ventral aspects of the developing forelimb bud and in the developing pharyngeal arches, as well as in the midbrain (PubMed:24906020).|||Expressed in the developing dorsal midbrain, the posterior portion of the mesencephalon and the retinal primordium of the optic cup. At 10 dpc, expressed in the temporal and nasal aspect of the retina and throughout the length of the dorsal midbrain. At 10.5 dpc this retinal pattern of expression persists, and extraneural sites of expression include the branchial region, limb buds and intestine. Also highly expressed in the alar mesencephalon and the rhombencephalic basal plate from 10.5 dpc to 14.5 dpc, and in the posterior third of the tectum and the presumptive gut wall. Also strongly expressed in the hindbrain, optic vesicle, maxillary and mandible process, paraxial mesoderm, developing digits and the umbilical cord.|||Nucleus|||Required for several aspects of embryonic development including normal development of the eye, notochord, neural tube and other organ tissues, and for embryonic turning. http://togogenome.org/gene/10090:Med12l ^@ http://purl.uniprot.org/uniprot/A0A0G2JET8|||http://purl.uniprot.org/uniprot/Q8BQM9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 12 family.|||May be a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||May be a component of the Mediator complex, which is known to be composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fcna ^@ http://purl.uniprot.org/uniprot/O70165|||http://purl.uniprot.org/uniprot/Q4FJM1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ficolin lectin family.|||Cell membrane|||Extracellular lectin functioning as a pattern-recognition receptor in innate immunity. Binds the sugar moieties of pathogen-associated molecular patterns (PAMPs) displayed on microbes and activates the lectin pathway of the complement system. May also activate monocytes through a G protein-coupled receptor, FFAR2, inducing the secretion of interleukin-8/IL-8. Binds preferentially to 9-O-acetylated 2-6-linked sialic acid derivatives and to various glycans containing sialic acid engaged in a 2-3 linkage (By similarity).|||Highly expressed in liver and spleen.|||Homotrimer. Interacts with elastin/ELN. Interacts (via Fibrinogen C-terminal domain) with FFAR2. Interacts with CRP; may regulate monocyte activation by FCN1.|||Secreted|||The fibrinogen C-terminal domain mediates calcium-dependent binding to carbohydrates and tethering to the cell surface in monocytes and granulocytes. The domain undergoes a conformational switch at pH under 6.2, and looses its carbohydrate-binding ability. http://togogenome.org/gene/10090:Tlcd1 ^@ http://purl.uniprot.org/uniprot/Q99JT6 ^@ Caution|||Function|||Subcellular Location Annotation ^@ Cell membrane|||Regulates the composition and fluidity of the plasma membrane (By similarity). Inhibits the incorporation of membrane-fluidizing phospholipids containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA) and thereby promotes membrane rigidity (By similarity). Does not appear to have any effect on LCPUFA synthesis (By similarity).|||Was originally proposed to be a calcium channel facilitator (By similarity). However, a more recent study shows that this protein regulates membrane phospholipid homeostasis (By similarity). Therefore, any effects on calcium flux are most likely a secondary consequence of defects in membrane composition or fluidity (By similarity). http://togogenome.org/gene/10090:Nr4a2 ^@ http://purl.uniprot.org/uniprot/Q06219|||http://purl.uniprot.org/uniprot/Q3TYI4 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR4 subfamily.|||Brain.|||Cytoplasm|||Expression begins in the embryo, increases in neonates and decreases in the adult.|||Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3. Interacts with PER2.|||Nucleus|||Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development (PubMed:19144721). It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (PubMed:19144721).|||the ligand-binding domain (LBD) contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. NR4A2 lacks a 'classical' binding site for coactivators (By similarity). http://togogenome.org/gene/10090:Krtap6-2 ^@ http://purl.uniprot.org/uniprot/O08884 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 6 family.|||Expressed in skin during two hair growth cycles. Expression restricted to the cortical cells of hair follicles, appearing first in the cortical cells processing the flat nuclei located a few cells above the dermal papilla.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:N6amt1 ^@ http://purl.uniprot.org/uniprot/Q6SKR2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic/archaeal PrmC-related family.|||Early embryonic lethality (PubMed:20606008). The postimplantation development of mutant embryos is impaired, resulting in degeneration around embryonic day 6.5 (PubMed:20606008).|||Heterodimer; heterodimerization with TRMT112 is required for S-adenosyl-L-methionine-binding.|||Highly expressed in undifferentiated embryonic stem cells (at protein level) (PubMed:19116772). Also expressed in testis and brain, weakly expressed in differentiated embryonic stem cells and kidney (PubMed:19116772). Not expressed in muscle, heart, placenta, pancreas, lung and stomach (PubMed:19116772).|||Methyltransferase that can methylate proteins and, to a lower extent, arsenic (PubMed:20606008, PubMed:26797129). Catalytic subunit of a heterodimer with TRMT112, which monomethylates 'Lys-12' of histone H4 (H4K12me1), a modification present at the promoters of numerous genes encoding cell cycle regulators (By similarity). Catalytic subunit of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif (PubMed:26797129). Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated (PubMed:20606008, PubMed:26797129). May also play a role in the modulation of arsenic-induced toxicity by mediating the conversion of monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid (By similarity). It however only plays a limited role in arsenic metabolism compared with AS3MT (By similarity).|||Nucleus|||Ubiquitinated, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Ubxn4 ^@ http://purl.uniprot.org/uniprot/Q8VCH8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Directly interacts with VCP. Interacts with UBQLN1. Forms a complex with VCP and UBQLN1.|||Endoplasmic reticulum membrane|||Expressed in many tissues, including brain, heart, kidney, liver, muscle and spleen (at protein level).|||Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD.|||Nucleus envelope|||The UBX domain is required for interaction with VCP.|||The intramembrane domain also contains the signal for ER targeting. http://togogenome.org/gene/10090:Spata16 ^@ http://purl.uniprot.org/uniprot/Q8C636 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SPATA16 family.|||Essential for spermiogenesis and male fertility (PubMed:29065458). Involved in the formation of acrosome during spermatogenesis (PubMed:16372119).|||Golgi apparatus|||Male mice are infertile with spermiogenic arrest and impaired differentiation of round spermatids into the mature spermatozoa.|||Testis-specific. Expressed in spermatocytes and round and elongated spermatids in the seminiferous tubules.|||acrosome http://togogenome.org/gene/10090:Atp9b ^@ http://purl.uniprot.org/uniprot/A0A286YCV0|||http://purl.uniprot.org/uniprot/D3YV00|||http://purl.uniprot.org/uniprot/P98195 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Found in most tissues except spleen and muscle. Most abundant in testis. Also detected in fetal tissues.|||Membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:H2-M10.6 ^@ http://purl.uniprot.org/uniprot/Q85ZW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Nrip1 ^@ http://purl.uniprot.org/uniprot/Q8CBD1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation abolishes interaction with CTBP1. Phosphorylation enhances interaction with YWHAH (By similarity). Acetylation regulates its nuclear translocation and corepressive activity.|||Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have different affinities for nuclear receptors.|||Contains at least 4 autonomous repression domains (RD1-4).|||Expressed in the embryonic placenta. In the adult, expression is strong in the testis and brain. Also expressed at a high level in the white adipose tissue. Expressed constantly but at a weaker level in the adult heart, lung, stomach and kidney. Expressed moderately in the skeletal muscle. Expressed at a low level in the adult spleen, liver and brown adipose tissue. Expressed in the ovary at a high level in granulosa cells and at a lower level in the thecal and interstitial compartments.|||Interacts with CTBP1, CTBP2, ERS1, HDAC1, HDAC2, HDAC5, HDAC6, NR2C2, NR3C1, NR3C2, YWHAH, JUN and FOS. Found in a complex with both NR3C1 and YWHAH (By similarity). Interacts with NR2C1 (sumoylated form and via the ligand-binding domain); the interaction results in promoting the repressor activity of NR2C1. Interacts with RARA and RXRB homodimers and RARA/RXRB heterodimers in the presence of ligand. Interacts with HDAC1 and HDAC3 via its N-terminal domain. Interacts with ZNF366 (By similarity). Interacts with RORA.|||Mice are viable and morphologically normal, but smaller than wild-type and heterozygous littermates. Homozygous NRIP1-null mature female are defective in ovulation and completely infertile (PubMed:11100122). Embryos with heterozygous NRIP1 loss show anomalies of the urinary tract including dysplastic kidneys with cystic dilations, severe hydoureter with hydronephrosis and ureterocele (PubMed:28381549).|||Modulates transcriptional repression by nuclear hormone receptors such as NR2C1, thyroid hormone receptor and retinoic acid receptor/RARA. Essential for cumulus expansion and follicle rupture during ovulation. Also controls the balance between fat accumulation and energy expenditure. Positive regulator of the circadian clock gene expression: stimulates transcription of BMAL1, CLOCK and CRY1 by acting as a coactivator for RORA and RORC. Involved in the regulation of ovarian function (PubMed:11100122). Plays a role in renal development (PubMed:28381549).|||Nucleus|||The Ligand-dependent nuclear receptor binding region is required for ligand-dependent interaction with RAAR and RXRB homo- and heterodimers, for the corepressor activity, and for the formation of an HDAC3 complex with RARA/RXRB. http://togogenome.org/gene/10090:Hoxd3 ^@ http://purl.uniprot.org/uniprot/P09027|||http://purl.uniprot.org/uniprot/Q3UZR4 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Antp homeobox family.|||Detected in 12-, 14-, and 17-day-old mouse embryos in the posterior half of the myelencephalon, spinal cord, dorsal root ganglia, first cervical vertebra, thyroid gland, kidney tubules, esophagus, stomach, and intestines.|||Detected in adult kidney, but not in other adult tissues tested.|||It is uncertain whether Met-1 or Met-17 is the initiator.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Elavl2 ^@ http://purl.uniprot.org/uniprot/B1AXZ4|||http://purl.uniprot.org/uniprot/B1AXZ5|||http://purl.uniprot.org/uniprot/Q3UR02|||http://purl.uniprot.org/uniprot/Q564D8|||http://purl.uniprot.org/uniprot/Q60899|||http://purl.uniprot.org/uniprot/Q80UJ0|||http://purl.uniprot.org/uniprot/Q80Y51 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RRM elav family.|||Brain; neural-specific (PubMed:8668530). Expressed in the hippocampus (PubMed:11573004).|||Interacts with IGF2BP1 (By similarity). Interacts with MAP1B light chain LC1 (PubMed:21288476).|||RNA-binding protein that binds to the 3' untranslated region (3'UTR) of target mRNAs (PubMed:8668530). Seems to recognize a GAAA motif (PubMed:8668530). Can bind to its own 3'UTR, the FOS 3'UTR and the ID 3'UTR (PubMed:8668530).|||Up-regulated after memory training in radial arm maze experiments. http://togogenome.org/gene/10090:Mycbp ^@ http://purl.uniprot.org/uniprot/Q9EQS3 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AMY1 family.|||Binds via its C-terminal region to the N-terminal region of MYC. Associates with AKAP1/S-AKAP84. Interacts with MYCBPAP. Interacts with CFAP91.|||Cytoplasm|||MYCBP expression is synergistically activated by SP1 and GATA-1.|||May control the transcriptional activity of MYC. Stimulates the activation of E box-dependent transcription by MYC (By similarity).|||Nucleus http://togogenome.org/gene/10090:BC028528 ^@ http://purl.uniprot.org/uniprot/Q8R2K8 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Lag3 ^@ http://purl.uniprot.org/uniprot/Q61790 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An initial knockout experiment in mouse reported only minor phenotype with no development of spontaneous disease, arguing against a significant role in controlling T-cell activation (PubMed:8602528). However, subsequent analysis showed that knockout mice develop autoimmune diseases caused by T-cell activation (PubMed:21873518).|||Belongs to the LAG3 family.|||Cell membrane|||Interacts with MHC class II (MHC-II); selectively recognizes stable complexes of peptide and MHC-II (PubMed:12209638, PubMed:12421911, PubMed:30349037). Interacts with FGL1 (via the Fibrinogen C-terminal domain) (PubMed:30580966).|||Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887, PubMed:30580966). Delivers inhibitory signals upon binding to ligands, such as FGL1 (PubMed:30580966). FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function (PubMed:30580966). Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887). May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1 (PubMed:21300912). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:12209638, PubMed:12421911, PubMed:12672063, PubMed:15100286, PubMed:15634887). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (PubMed:15485628). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (PubMed:19201841). Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear (PubMed:12209638, PubMed:12421911, PubMed:15634887).|||May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response.|||Mice develop normally but show minor defects in the natural killer (NK) cells (PubMed:8602528). They are however prone to development of autoimmune diseases, such as autoimmune diabetes on a permissive genetic background (PubMed:21300912, PubMed:21873518). Knockout NOD mice exhibit accelerated, invasive insulitis, corresponding to increased CD4(+) and CD8(+) T-cell islet infiltration and intraislet proliferation (PubMed:21873518). T-cells display a delay in cell cycle arrest following stimulation with the superantigen staphylococcal enterotoxin-B resulting in increased T-cell expansion and splenomegaly (PubMed:15100286). Mice lacking both Lag3 and Pdcd1/PD-1 die of severe myocarditis before 10 weeks of age in BALB/c mice (PubMed:21300912).|||Primarily expressed in activated CD4(+) and CD8(+) T-cells (PubMed:12209638). Also expressed in a subset of regulatory T-cells (Tregs), such as natural CD4(+)CD25(+) Tregs (PubMed:15485628). Also expressed on plasmacytoid dendritic cells (pDCs) (PubMed:19201841).|||Proteolytically cleaved by ADAM10 and ADAM17 within the connecting peptide region, leading to release of Secreted lymphocyte activation gene 3 protein (sLAG-3) (PubMed:17245433). ADAM10 mediates constitutive cleavage, but cleavage increases following T-cell activation, whereas shedding by ADAM17 is induced by TCR signaling in a PRKCQ-dependent manner (PubMed:17245433).|||Secreted|||The KIEELE motif is required for interaction with downstream signaling molecules. http://togogenome.org/gene/10090:G3bp2 ^@ http://purl.uniprot.org/uniprot/P97379 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Can mediate both protein-protein and protein-RNA interactions via the NTF2 domain and RNA-binding domain RRM; protein-protein and protein-RNA interactions are essential for undergoing liquid-liquid phase separation (LLPS).|||Cytoplasm|||Forms homooligomers. Forms heterodimers with G3BP1. Interacts with NFKBIA (via N-terminus). Interacts (via NTF2 domain) with USP10; inhibiting stress granule formation. Interacts (via NTF2 domain) with CAPRIN1; promoting stress granule formation. Associates (via RG-rich region) with 40S ribosome subunits. Interacts with PABPC1.|||Scaffold protein that plays an essential role in cytoplasmic stress granule formation which acts as a platform for antiviral signaling. Plays an essential role in stress granule formation. Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress (By similarity). Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations (By similarity).|||Stress granule|||The NTF2 domain mediates interaction with CAPRIN1 and USP10 regulators, thereby regulating assembly of stress granules.|||The acidic disordered region acts as a negative regulator of phase separation.|||Under physiological conditions, G3BP2 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation. Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state. Binding of unfolded mRNA to G3BP2 outcompetes the intramolecular interactions and RNA-bound G3BP2 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS). http://togogenome.org/gene/10090:Ccl4 ^@ http://purl.uniprot.org/uniprot/P14097|||http://purl.uniprot.org/uniprot/Q5QNV9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intercrine beta (chemokine CC) family.|||Homodimer.|||Monokine with inflammatory and chemokinetic properties.|||Secreted http://togogenome.org/gene/10090:Sqstm1 ^@ http://purl.uniprot.org/uniprot/Q64337 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophagy receptor required for selective macroautophagy (aggrephagy) (By similarity). Functions as a bridge between polyubiquitinated cargo and autophagosomes (By similarity). Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family (By similarity). Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures) (By similarity). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus (By similarity). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (By similarity). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (By similarity). May play a role in titin/TTN downstream signaling in muscle cells (By similarity). May regulate signaling cascades through ubiquitination (By similarity). Adapter that mediates the interaction between TRAF6 and CYLD (PubMed:14960283, PubMed:18382763). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels (By similarity). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (By similarity). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (By similarity). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20421418, PubMed:20173742, PubMed:24011591). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (By similarity).|||By diethylmaleate, paraquat, menadione, sodium arsenite and cadmium chloride, arsenite and arsenate. By MG132, MG115, lactacystin and proteasome inhibitor I (PSI). By serum starvation, okadaic acid and glucose oxidase. Also up-regulated by RANK-L (at protein level). By etoposide and trichostatin. By the parkinsonian mimetic 6-hydroxydopamine (6-OHDA). By TGF-beta.|||Endoplasmic reticulum|||Homooligomer or heterooligomer; may form homotypic arrays (PubMed:20173742). Interacts directly with PRKCI and PRKCZ (Probable). Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM13, TRIM55 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with AJUBA, PRKCZ and TRAF6. Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (By similarity). Interacts with TRAF6 and CYLD. Identified in a complex with TRAF6 and CYLD. Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 family members, including GABARAP, GABARAPL1 and GABARAPL2; these interactions are necessary for the recruitment MAP1 LC3 family members to inclusion bodies containing polyubiquitinated protein aggregates and for their degradation by autophagy (By similarity). Interacts with FHOD3 (By similarity). Interacts with TRMI5 (By similarity). Interacts with SESN1 (By similarity). Interacts with SESN2 (PubMed:25040165). Interacts with ULK1 (PubMed:25040165). Interacts with UBD (By similarity). Interacts with WDR81; the interaction is direct and regulates the interaction of SQSTM1 with ubiquitinated proteins (By similarity). Interacts with WDFY3; this interaction is required to recruit WDFY3 to cytoplasmic bodies and to PML bodies (By similarity). Interacts with TRIM23 (By similarity). Interacts with LRRC25. Interacts with TRIM50 (PubMed:22792322). Interacts with TRIM16 (By similarity). Interacts with STING1; leading to relocalization of STING1 to autophagosomes (By similarity). Interacts (when phosphorylated at Ser-351) with KEAP1; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering KEAP1 in inclusion bodies, promoting its degradation (PubMed:20495340, PubMed:20421418, PubMed:20173742). Interacts with GBP1 (PubMed:21551061). Interacts with MOAP1; promoting dissociation of SQSTM1 inclusion bodies that sequester KEAP1 (By similarity). Interacts with TAX1BP1 (By similarity). Interacts with (ubiquitinated) PEX5; specifically binds PEX5 ubiquitinated at 'Lys-209' in response to reactive oxygen species (ROS) (By similarity). Interacts (via PB1 domain) with TNS2; the interaction leads to sequestration of TNS2 in cytoplasmic aggregates with SQSTM1 and promotes TNS2 ubiquitination and proteasomal degradation (By similarity). Interacts with IRS1; the interaction is disrupted by the presence of tensin TNS2 (By similarity). Interacts with TRIM11 (when ubiquitinated); promoting AIM2 recruitment to autophagosomes and autophagy-dependent degradation of AIM2 (By similarity). Interacts with ECSIT; this interaction inhibits TLR4 signaling via functional regulation of the TRAF6-ECSIT complex (By similarity).|||Impaired induced osteoclastogenesis.|||Late endosome|||Lysosome|||Nucleus|||PML body|||Phosphorylated. May be phosphorylated by PRKCZ. Phosphorylated in vitro by TTN (By similarity). Phosphorylation at Ser-405 by ULK1 is stimulated by SESN2 (By similarity). Phosphorylated at Ser-405 by TBK1, leading to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (By similarity). Phosphorylation at Ser-351 by MTOR promotes interaction with KEAP1 and inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:24011591).|||Preautophagosomal structure|||The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.|||The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.|||The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.|||The ZZ-type zinc finger mediates the interaction with RIPK1.|||Ubiquitinated by UBE2J1 and RNF26 at Lys-437: ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Deubiquitination by USP15 releases target vesicles for fast transport into the cell periphery. Ubiquitinated by the BCR(KEAP1) complex at Lys-422, increasing SQSTM1 sequestering activity and promoting its degradation. Ubiquitinated via 'Lys-29' and 'Lys-33'-linked polyubiquitination leading to xenophagic targeting of bacteria and inhibition of their replication.|||Widely expressed.|||autophagosome|||cytosol|||sarcomere http://togogenome.org/gene/10090:Pnpla8 ^@ http://purl.uniprot.org/uniprot/Q8K1N1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release of lipid second messengers and growth factors (PubMed:17923475, PubMed:28442572). Hydrolyzes phosphatidylethanolamine, phosphatidylcholine and probably phosphatidylinositol with a possible preference for the former. Has also a broad substrate specificity in terms of fatty acid moieties, hydrolyzing saturated and mono-unsaturated fatty acids at nearly equal rates from either the sn-1 or sn-2 position in diacyl phosphatidylcholine. However, has a weak activity toward polyunsaturated fatty acids at the sn-2 position, and thereby favors the production of 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling. On the other hand, can produce arachidonic acid from the sn-1 position of diacyl phospholipid and from the sn-2 position of arachidonate-containing plasmalogen substrates. Therefore, plays an important role in the mobilization of arachidonic acid in response to cellular stimuli and the generation of lipid second messengers. Can also hydrolyze lysophosphatidylcholine (By similarity). In the mitochondrial compartment, catalyzes the hydrolysis and release of oxidized aliphatic chains from cardiolipin and integrates mitochondrial bioenergetics and signaling. It is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition (PubMed:17923475, PubMed:28442572).|||Calcium-independent phospholipase.|||Endoplasmic reticulum membrane|||Expressed in myocardium (at protein level).|||Mitochondrion membrane|||Mutants display multiple bioenergetic dysfunctional phenotypes, including growth retardation, cold intolerance, reduced exercise endurance, greatly increased mortality from cardiac stress after transverse aortic constriction, abnormal mitochondrial function with a 65% decrease in ascorbate-induced Complex IV-mediated oxygen consumption, and a reduction in myocardial cardiolipin content accompanied by an altered cardiolipin molecular species composition. Myocardium of mutant mice contain more oxidized cardiolipin (PubMed:28442572).|||Peroxisome membrane http://togogenome.org/gene/10090:Or5b120 ^@ http://purl.uniprot.org/uniprot/Q7TQQ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rasd2 ^@ http://purl.uniprot.org/uniprot/P63032 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. RasD family.|||Cell membrane|||Contaminating sequence.|||Down-regulated in hypothyroid conditions and up-regulated by glibenclamide.|||Expressed in the brain from 13.5 dpc.|||Farnesylated. Farnesylation is required for membrane targeting (By similarity).|||GTPase signaling protein that binds to and hydrolyzes GTP. Regulates signaling pathways involving G-proteins-coupled receptor and heterotrimeric proteins such as GNB1, GNB2 and GNB3. May be involved in selected striatal competencies, mainly locomotor activity and motor coordination.|||Highly expressed in brain; prominently in the striatum and weakly in kidney, thyroid, lung, heart and testis. Not expressed in liver. Expressed in pancreatic cell lines and in a embryonic stem cell line.|||Monomer (Potential). Interacts with PIK3CA and UBE2I. Interacts with GNB1, GNB2 and GNB3 (By similarity).|||Shows behavioral abnormalities, displaying a gender-dependent increase in anxiety levels and a clear motor coordination deficit and a mild hyperactive phenotype. Mice are more sensitive to D2 receptor stimulation and have decreased body weight. http://togogenome.org/gene/10090:Rogdi ^@ http://purl.uniprot.org/uniprot/Q3TDK6 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rogdi family.|||Detected in brain, kidney and testis.|||Monomer.|||Nucleus envelope|||Perikaryon|||Presynapse|||axon|||dendrite|||synaptic vesicle http://togogenome.org/gene/10090:Vmn1r178 ^@ http://purl.uniprot.org/uniprot/Q8R2B6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ace2 ^@ http://purl.uniprot.org/uniprot/Q3URC9|||http://purl.uniprot.org/uniprot/Q8R0I0 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Weakly interacts with SARS-CoV S protein.|||Apical cell membrane|||Belongs to the peptidase M2 family.|||Binds 1 Cl(-) ion per subunit.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Cytoplasm|||Down-regulated in lung after acute injury. Exposure to cigarette smoke increases ACE2 expression up to 80% more in lungs (PubMed:32425701).|||Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins, casomorphins and dynorphin A (By similarity). By cleavage of angiotensin II, may be an important regulator of heart function (PubMed:12075344, PubMed:12967627). By cleavage of angiotensin II, may also have a protective role in acute lung injury (PubMed:16001071). Plays an important role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19, regulating its trafficking on the cell surface and its activity (PubMed:19185582, PubMed:18424768, PubMed:22677001).|||Expressed in heart, kidney and forebrain (at protein level). Expressed in the small intestine, with expression in the intestinal brush border (at protein level) (PubMed:19185582, PubMed:22677001). Ubiquitously expressed, with highest levels in ileum, kidney and lung. In lung, expressed on vascular endothelial and airway epithelial cells. Also expressed at high levels in lung secretory club and goblet cells as well as in alveolar type 2 cells (PubMed:32425701).|||Homodimer. Interacts with the catalytically active form of TMPRSS2 (By similarity). Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine (PubMed:19185582). Interacts with ITGA5:ITGB1 (By similarity). Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781 (By similarity). Interacts (via PDZ-binding motif) with NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane residence (By similarity).|||Membrane|||Mice are viable and fertile, exhibit normal kidney and lung function, but show a severe reduction in cardiac contractility, and are highly sensitive to severe acute lung failure (PubMed:12075344). Mutant males exhibit an absence of SLC6A19 in small intestine brush border membranes, but normal SLC6A19 expression in kidney (PubMed:19185582). Abolished sodium-dependent transport of isoleucine in intestinal rings (PubMed:19185582). Transgenic mice overexpressing ACE2 in the heart appear healthy but show conduction disturbances and ventricular arrhythmias which leads to sudden death (PubMed:12075344).|||Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains.|||Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1 (By similarity).|||Secreted|||The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interaction with proteins that mediate endocytic trafficking and autophagy.|||cilium http://togogenome.org/gene/10090:Ints7 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0E4|||http://purl.uniprot.org/uniprot/Q7TQK1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 7 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. Interacts with NABP2.|||Chromosome|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Plays a role in DNA damage response (DDR) signaling during the S phase. May be not involved in the recruitment of cytoplasmic dynein to the nuclear envelope by different components of the INT complex.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Isg20l2 ^@ http://purl.uniprot.org/uniprot/Q3U1G5 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ 3'-> 5'-exoribonuclease involved in ribosome biogenesis in the processing of the 12S pre-rRNA. Displays a strong specificity for a 3'-end containing a free hydroxyl group.|||Contaminating sequence. Sequence of unknown origin.|||nucleolus http://togogenome.org/gene/10090:Akap4 ^@ http://purl.uniprot.org/uniprot/A1L3T6|||http://purl.uniprot.org/uniprot/Q60662 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AKAP110 family.|||Interacts with PRKAR1A and PRKAR2A (PubMed:9852104). Interacts with ENO4 (PubMed:23446454).|||Major structural component of sperm fibrous sheath. Plays a role in sperm motility (PubMed:12167408).|||Post-meiotic phase of spermatogenesis.|||RI-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.|||Spermatid.|||flagellum http://togogenome.org/gene/10090:Trp53inp1 ^@ http://purl.uniprot.org/uniprot/Q3UQK9|||http://purl.uniprot.org/uniprot/Q9QXE4 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiproliferative and proapoptotic protein involved in cell stress response which acts as a dual regulator of transcription and autophagy. Acts as a positive regulator of autophagy. In response to cellular stress or activation of autophagy, relocates to autophagosomes where it interacts with autophagosome-associated proteins GABARAP, GABARAPL1/L2, MAP1LC3A/B/C and regulates autophagy. Acts as an antioxidant and plays a major role in p53/TP53-driven oxidative stress response. Possesses both a p53/TP53-independent intracellular reactive oxygen species (ROS) regulatory function and a p53/TP53-dependent transcription regulatory function. Positively regulates p53/TP53 and p73/TP73 and stimulates their capacity to induce apoptosis and regulate cell cycle. In response to double-strand DNA breaks, promotes p53/TP53 phosphorylation on 'Ser-46' and subsequent apoptosis. Acts as a tumor suppressor by inducing cell death by an autophagy and caspase-dependent mechanism. Can reduce cell migration by regulating the expression of SPARC.|||By adriamycin, methymethane sulfonate, ethanol, H(2)O(2), ultraviolet irradiation and heat shock. Rapidly induced in acinar cells of the pancreas with acute pancreatitis upon caerulein treatment.|||Cytoplasm|||Interacts with p53/TP53 and HIPK2. Interacts with PRKCG, GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C.|||Nucleus|||PML body|||The LC3 interacting region (LIR) motif mediates interaction with GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C.|||Ubiquitously expressed with highest levels in the thymus.|||autophagosome|||cytosol http://togogenome.org/gene/10090:Or5al7 ^@ http://purl.uniprot.org/uniprot/Q8VFK4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Traf4 ^@ http://purl.uniprot.org/uniprot/Q61382 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein with E3 ligase activity that is involved in many diverse biological processes including cell proliferation, migration, differentiation, DNA repair, platelet activation or apoptosis. Promotes EGFR-mediated signaling by facilitating the dimerization of EGFR and downstream AKT activation thereby promoting cell proliferation. Ubiquitinates SMURF2 through 'Lys-48'-linked ubiquitin chain leading to SMURF2 degradation through the proteasome and subsequently osteogenic differentiation. Promotes 'Lys-63'-mediated ubiquitination of CHK1 which in turn activates cell cycle arrest and activation of DNA repair. In addition, promotes an atypical 'Lys-29'-linked ubiquitination at the C-terminal end of IRS1 which is crucial for insulin-like growth factor (IGF) signal transduction (By similarity). Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract. Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions. Inhibits adipogenic differentiation by activating pyruvate kinase PKM activity and subsequently the beta-catenin signaling pathway (By similarity).|||Belongs to the TNF receptor-associated factor family. B subfamily.|||Cell membrane|||Cytoplasm|||Homotrimer. Interacts with LTBR/TNFRSF3, NGFR/TNFRSF16, RPS6KB1 and TGFB1I1. Interacts with SMURF1. Interacts (via TRAF domain) with MAP3K4 (via kinase domain). Interacts with NCF1, TICAM1, IRAK1 and TRAF6, and is probably part of a complex containing TRAF4, NCF1, TICAM1, IRAK1 and TRAF6. Interacts (via MATH domain) with GP6 and GP1BB. Interacts with EGFR (via C-terminal region); this interaction promotes the formation of EGFR asymmetric dimers. Interacts with PKM; this interaction promotes PKM kinase activity.|||Mice exhibit considerable phenotypic variability, depending in part on the strain. In one strain pups are born at the expected Mendelian frequency, while in another strain up to one third die during embryogenesis. Mutants that reach adulthood are fertile, but have on average three pups per litter instead of ten in wild-type. Mutants have an apparently normal immune response, with no defects in the development of T and B-lymphocytes, granulocytes, macrophages and dendritic cells. Mutants have respiratory problems, due to developmental defects of the trachea, stem bronchi and rib cage. They exhibit severe skeletal alterations at the level of the spinal column, including scoliosis and kyphosis, and have curly tails. Many also display neural tube closure defects.|||Nucleus|||Polyubiquitinated, leading to its proteasomal degradation (By similarity). Ubiquitinated at Lys-263 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (PubMed:23542741).|||Predominantly expressed in brain. Preferentially expressed by postmitotic undifferentiated neurons in developing central (CNS) and peripheral (PNS) nervous system, and in nervous tissues of sensory organs. In the embryo, protein expression was shown in brain, thymus, salivary glands and intestine. In the adult, protein expression is restricted to the brain (hippocampus and olfactory bulb).|||Strongly expressed throughout embryogenesis with a maximum from 8.5 to 13.5 dpc.|||The MATH/TRAF domain binds to receptor cytoplasmic domains.|||The coiled coil domain mediates homo- and hetero-oligomerization.|||cytoskeleton|||perinuclear region|||tight junction http://togogenome.org/gene/10090:Or51a39 ^@ http://purl.uniprot.org/uniprot/Q8VGX7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Padi2 ^@ http://purl.uniprot.org/uniprot/Q08642|||http://purl.uniprot.org/uniprot/Q3TBF1 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein arginine deiminase family.|||Binding of Ca(2+) triggers a conformation change that is essential for catalytic activity.|||Catalyzes the deimination of arginine residues of proteins.|||Cytoplasm|||Expressed during the estrus cycle. Expressed during diestrus and proestrus with an eight fold decline when estrus cycle is reached.|||Expressed in various tissues including muscle, uterus, spinal cord, salivary gland and pancreas.|||Homodimer. http://togogenome.org/gene/10090:Itpka ^@ http://purl.uniprot.org/uniprot/Q8R071 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by calcium/calmodulin.|||Belongs to the inositol phosphokinase (IPK) family.|||Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.|||cytoskeleton http://togogenome.org/gene/10090:Borcs7 ^@ http://purl.uniprot.org/uniprot/Q9CRC6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.|||Belongs to the BORCS7 family.|||Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN.|||Lysosome membrane http://togogenome.org/gene/10090:Pck1 ^@ http://purl.uniprot.org/uniprot/Q9Z2V4 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated (PubMed:30193097). Lysine acetylation by p300/EP300 is increased on high glucose conditions and promotes ubiquitination by UBR5, acetylation is enhanced in the presence of BAG6. Deacetylated by SIRT2 (By similarity). Deacetylated by SIRT1 (PubMed:30193097).|||Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.|||Binds 1 Mn(2+) ion per subunit.|||Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:11916968, PubMed:11792850, PubMed:30193097, PubMed:29230018). Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:30193097). At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle (PubMed:30193097). At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate (PubMed:30193097). Acts as a regulator of formation and maintenance of memory CD8(+) T-cells: up-regulated in these cells, where it generates phosphoenolpyruvate, via gluconeogenesis (PubMed:29230018). The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis (PubMed:29230018). In addition to the phosphoenolpyruvate carboxykinase activity, also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor (By similarity). The protein kinase activity regulates lipogenesis: upon phosphorylation at Ser-90, translocates to the endoplasmic reticulum and catalyzes phosphorylation of INSIG proteins (INSIG1 and INSIG2), thereby disrupting the interaction between INSIG proteins and SCAP and promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes (By similarity).|||Endoplasmic reticulum|||Expression is repressed by ATF3 (PubMed:11916968). Expression is regulated by glucocortinoids and insulin (PubMed:16100117). Up-regulated in CD8(+) memory T-cells (PubMed:29230018).|||In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one.|||Mice do not survive beyond 2 to 3 days after birth.|||Monomer.|||Phosphoenolpyruvate carboxykinase activity is regulated by acetylation and glucose levels (PubMed:30193097). The anaplerotic conversion of phosphoenolpyruvate to oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473 (K473ac) and Lys-521 (K521ac) (By similarity). High glucose concentrations favor PCK1 anaplerotic activity by triggering acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated deacetylation of Lys-91 promotes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (By similarity). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity).|||Phosphorylated in a GSK3B-mediated pathway; phosphorylation affects the efficiency of SIRT1-mediated deacetylation, and regulates PCK1 ubiquitination and degradation. Phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes the protein kinase activity: phosphorylated PCK1 translocates to the endoplasmic reticulum, where it phosphorylates INSIG1 and INSIG2.|||Ubiquitination by UBR5 leads to proteasomal degradation.|||cytosol http://togogenome.org/gene/10090:Tbc1d2b ^@ http://purl.uniprot.org/uniprot/Q3U0J8 ^@ Function|||Subcellular Location Annotation ^@ Early endosome|||GTPase-activating protein that plays a role in the early steps of endocytosis. http://togogenome.org/gene/10090:Or4c120 ^@ http://purl.uniprot.org/uniprot/Q7TR01 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tdrd12 ^@ http://purl.uniprot.org/uniprot/Q9CWU0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subunit|||Tissue Specificity ^@ Component of a mRNP complex containing PIWIL2, TDRD1 and piRNAs (PubMed:24067652). Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs (PubMed:26669262).|||Expressed from embryonic to the adult stages in testis. Expressed in embryonic stem (ES) cells.|||Mice are viable but show male sterility with chromosome synapsis failure. Male mice display atrophied testes, with seminiferous tubules that are narrow with large vacuolated spaces, devoid of late-stage germ cells. Retrotransposons are derepressed due to DNA demethylation.|||Probable ATP-binding RNA helicase required during spermatogenesis to repress transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:24067652). Involved in the secondary piRNAs metabolic process (PubMed:24067652). Acts via the PET complex, a multiprotein complex required during the secondary piRNAs metabolic process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs (PubMed:26669262).|||Restricted to the gonads. http://togogenome.org/gene/10090:Pold1 ^@ http://purl.uniprot.org/uniprot/P52431 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As the catalytic component of the trimeric (Pol-delta3 complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 complex), plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence (Pol-delta3) or the presence of POLD4 (Pol-delta4), displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine, 8oxoG or abasic sites.|||Belongs to the DNA polymerase type-B family.|||Binds 1 [4Fe-4S] cluster.|||Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5' proofreading exonuclease activities. Within Pol-delta4, directly interacts with POLD2 and POLD4. Following genotoxic stress by DNA-damaging agents, such as ultraviolet light and methyl methanesulfonate, or by replication stress induced by treatment with hydroxyurea or aphidicolin, Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form at S phase replication sites and DNA damage sites. POLD1 displays different catalytic properties depending upon the complex it is found in. It exhibits higher proofreading activity and fidelity than Pol-delta4, making it particularly well suited to respond to DNA damage. Directly interacts with PCNA, as do POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase activity. As POLD2 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity. Also observed as a dimeric complex with POLD2 (Pol-delta2). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. The DNA polymerase delta complex interacts with POLDIP2; this interaction is probably mediated through direct binding to POLD2. Interacts with CIAO1. Interacts with POLDIP2 (By similarity).|||Nucleus|||Regulated by alteration of quaternary structure. Exhibits burst rates of DNA synthesis are about 5 times faster in the presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 complex), while the affinity of the enzyme for its DNA and dNTP substrates appears unchanged. The Pol-delta3 complex is more likely to proofread DNA synthesis because it cleaves single-stranded DNA twice as fast and transfers mismatched DNA from the polymerase to the exonuclease sites 9 times faster compared to the Pol-delta3 complex. Pol-delta3 also extends mismatched primers 3 times more slowly in the absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is induced by genotoxic stress or by replication stress leading POLD4 degradation. Stimulated in the presence of PCNA (By similarity). This stimulation is further increased in the presence of KCTD13/PDIP1, most probably via direct interaction between KCTD13 and POLD2 (By similarity).|||The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes. http://togogenome.org/gene/10090:Mdh1 ^@ http://purl.uniprot.org/uniprot/A0A5F8MPN8|||http://purl.uniprot.org/uniprot/P14152 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-118 dramatically enhances enzymatic activity and promotes adipogenic differentiation.|||Belongs to the LDH/MDH superfamily. MDH type 2 family.|||Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH. Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation. Catalyzes the reduction of 2-oxoglutarate to 2-hydroxyglutarate, leading to elevated reactive oxygen species (ROS).|||Homodimer.|||ISGylated.|||cytosol http://togogenome.org/gene/10090:Troap ^@ http://purl.uniprot.org/uniprot/B7ZNG4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation.|||Cytoplasm|||Directly binds bystin, and indirectly trophinin. http://togogenome.org/gene/10090:Ncstn ^@ http://purl.uniprot.org/uniprot/P57716 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nicastrin family.|||Component of the gamma-secretase complex. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2 (PubMed:12716934). Binds to proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Interacts with PSEN1 and PSEN2.|||Cytoplasmic vesicle membrane|||Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels.|||Full embryonic lethality. No embryos survive past 10.d dpc. At 9.5 dpc the embryos display a phenotype similar to that of Notch1-deficient mice, with defects in the development of the caudal part of the embryo and in somite segementation, defective vascular morphogenesis in the yolk sac, and patterning defects in the developing heart and neural tube. Assembly of the gamma-secretase complex and APP processing are disrupted.|||Melanosome|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Zmat2 ^@ http://purl.uniprot.org/uniprot/Q9CPW7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the spliceosome B complex.|||Involved in pre-mRNA splicing as a component of the spliceosome.|||Nucleus http://togogenome.org/gene/10090:Smdt1 ^@ http://purl.uniprot.org/uniprot/Q9DB10 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMDT1/EMRE family.|||Component of the uniplex complex, composed of MCU, MCUB, MICU1, MICU2 and EMRE/SMDT1 (By similarity). Interacts (via the transmembrane region) with MCU (via the first transmembrane region); the interaction is direct (PubMed:27001609). Interacts (via the poly-Asp region) with MICU1 (via polybasic region); the interaction is direct (By similarity). Interacts (via its C-terminal poly-Asp tail) with MCUR1; the interaction is direct (By similarity). Unprocessed form interacts (via transit peptide) with MAIP1 (By similarity).|||Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria (PubMed:27001609). Required to bridge the calcium-sensing proteins MICU1 and MICU2 with the calcium-conducting subunit MCU. Plays a central role in regulating the uniplex complex response to intracellular calcium signaling. Acts by mediating activation of MCU and retention of MICU1 to the MCU pore, in order to ensure tight regulation of the uniplex complex and appropriate responses to intracellular calcium signaling (By similarity).|||Mitochondrion inner membrane|||The GXXXX[G/A/S] motif at the C-terminal part of the transmembrane region mediates interaction with MCU and is required to activate the calcium-conducting pore in the uniporter complex.|||The poly-Asp region at the C-terminus mediates interaction with the polybasic region of MICU1.|||Undergoes proteolytic degradation in neurons: degraded by AFG3L2 before SMDT1/EMRE assembly with the uniporter complex, limiting the availability of SMDT1/EMRE for MCU assembly and promoting efficient assembly of gatekeeper subunits with MCU.|||Widely expressed. http://togogenome.org/gene/10090:Or5w18 ^@ http://purl.uniprot.org/uniprot/Q8VEU8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r81 ^@ http://purl.uniprot.org/uniprot/Q80Z09 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cpsf4 ^@ http://purl.uniprot.org/uniprot/B2LVG5|||http://purl.uniprot.org/uniprot/B2LVG6|||http://purl.uniprot.org/uniprot/Q8BQZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CPSF4/YTH1 family.|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U) (By similarity).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with FIP1L1 (By similarity).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex.|||Nucleus http://togogenome.org/gene/10090:Adam6b ^@ http://purl.uniprot.org/uniprot/Q6IMH7 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Nexn ^@ http://purl.uniprot.org/uniprot/Q7TPW1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with F-actin.|||Involved in regulating cell migration through association with the actin cytoskeleton. Has an essential role in the maintenance of Z line and sarcomere integrity.|||Z line|||adherens junction|||cytoskeleton http://togogenome.org/gene/10090:Parg ^@ http://purl.uniprot.org/uniprot/G3X8U8 ^@ Similarity ^@ Belongs to the poly(ADP-ribose) glycohydrolase family. http://togogenome.org/gene/10090:Aqp2 ^@ http://purl.uniprot.org/uniprot/P56402|||http://purl.uniprot.org/uniprot/Q3UQD4 ^@ Disease Annotation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Basolateral cell membrane|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Defects in Aqp2 are a cause of congenital progressive hydronephrosis (cph). Homozygous mice appear grossly normal at birth, but grow slowly, and 90% die between 2 and 4 weeks after birth. They display symptoms reminiscent of diabetes insipidus, with excessive water drinking (polydipsia), excessive urine excretion (polyuria), and persistent hypotonic urine. When older than 14 days, they nearly always display severe bilateral hydronephrosis resulting from impaired downward urine transport, in spite of the absence of physical blockage of the urinary tract. Surviving adults have a shortened lifespan and die at the latest at an age of 10 months. They display reduced fertility or are infertile.|||Detected in principal cells in the collecting duct in kidney medulla and cortex (at protein level) (PubMed:10191086, PubMed:16735444, PubMed:16641094, PubMed:31605441). Expressed in a radial pattern from the cortex through the outer medulla into the inner medulla (PubMed:12426236). Higher levels in the inner medulla (PubMed:12426236).|||Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (PubMed:10191086). Plays an essential role in renal water homeostasis (PubMed:16641094).|||Homotetramer.|||Increased levels on water deprivation.|||Membrane|||N-glycosylated.|||Ser-256 phosphorylation is necessary and sufficient for expression at the apical membrane (PubMed:16641094). Endocytosis is not phosphorylation-dependent (By similarity).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Pus7l ^@ http://purl.uniprot.org/uniprot/Q8CE46 ^@ Function|||Sequence Caution|||Similarity ^@ Belongs to the pseudouridine synthase TruD family.|||Probable cloning artifact. May result from internal priming due to genomic poly-A tracts.|||Pseudouridine synthase that catalyzes pseudouridylation of mRNAs. http://togogenome.org/gene/10090:Lcn11 ^@ http://purl.uniprot.org/uniprot/A2BHR2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Chit1 ^@ http://purl.uniprot.org/uniprot/B2RS82|||http://purl.uniprot.org/uniprot/Q9D7Q1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.|||Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens (By similarity).|||Highly expressed in tongue, stomach, kidney, brain, skin, testis, and bone marrow. Low level of expression was found in lung, heart, spleen, small intestine, and liver. Not detectable in pancreas, salivary gland, large intestine, uterus, or peripheral blood mononuclear cells (PBMC).|||Lysosome|||Monomer.|||Secreted http://togogenome.org/gene/10090:Kncn ^@ http://purl.uniprot.org/uniprot/Q307W7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ First detected in the kinocilia of vestibular and auditory hair cells at embryonic days 14.5, and 18.5, respectively. In the mature vestibular hair cells, it is still present in the kinocilium. As the auditory hair cells begin to lose the kinocilium during postnatal development, it becomes distributed in an annular pattern at the apex of these cells, where it colocalizes with the tubulin belt. In mature auditory hair cells, it is also present at the level of the cuticular plate, at the base of each stereocilium. As the kinocilium regresses from developing auditory hair cells, it begins to be expressed by the pillar cells and Deiters cells, that both contain prominent transcellular and apical bundles of microtubules. Not detected in the supporting cells in the vestibular end organs (at protein level).|||May play a role in stabilizing dense microtubular networks or in vesicular trafficking.|||Membrane|||Preferentially expressed in the inner ear and testis. Localizes mainly in the kinocilium of sensory cells in the inner ear. Also present in the manchette of the spermatids, a transient structure enriched in interconnected microtubules (at protein level). http://togogenome.org/gene/10090:Car5b ^@ http://purl.uniprot.org/uniprot/Q9QZA0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-carbonic anhydrase family.|||Mitochondrion|||Reversible hydration of carbon dioxide. http://togogenome.org/gene/10090:Per3 ^@ http://purl.uniprot.org/uniprot/O70361 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals show altered sleep and behavioral activity whitout changes in total activity or vigilance states. They have increased wheel-running activity and reduced REM (rapid eye movement) sleep and NREM (non-REM) sleep in the middle of the dark phase. At the beginning of the baseline light period, they have less wakefulness and more REM and NREM sleep. Mice spend less time in wakefulness and more time in NREM sleep on the light period immediately after sleep deprivation and REM sleep accumulates more slowly during the recovery dark phase. They also display a depression-like phenotype. Double knocknouts for PER2 and PER3 show the same phenotype as PER2 knockouts with severely disrupted circadian behavior.|||Cytoplasm|||Exhibits circadian oscillation expression in SCN, liver, skeletal muscle, testis and eyes. In the SCN, highest levels during subjective day at CT6 and CT9, lowest levels at night, CT15, CT18 and CT 21. In the liver, skeletal muscle, testis and eyes highest levels at CT15, CT15-CT18, CT9 and CT15, and CT9-CT15, respectively. During subjective night, unresponsive to light exposure.|||Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with PER1, PER2, CRY1, CRY2, and TIMELESS; interaction with CRY1 and CRY2 is weak and not rhythmic. Interacts with FBXW11 and BTRC.|||Nucleus|||Originally described as a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance. In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters. Can bind heme.|||Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus.|||Ubiquitinated.|||Widely expressed. Expressed in heart, brain, lung, liver, skeletal muscle, testis, and at low level in the spleen and kidney. In brain, mainly found in the SCN, hippocampus, piriform cortex, and cerebellum. Lower level of expression in the neocortex. Expression exhibits synchronous oscillations in liver, skeletal muscle and testis. http://togogenome.org/gene/10090:COX1 ^@ http://purl.uniprot.org/uniprot/P00397|||http://purl.uniprot.org/uniprot/Q9MD68 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heme-copper respiratory oxidase family.|||Binds 2 heme A groups non-covalently per subunit.|||Binds a copper B center.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). As a newly synthesized protein, rapidly incorporates into a multi-subunit assembly intermediate in the inner membrane, called MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) complex, whose core components are COA3/MITRAC12 and COX14. Within the MITRAC complex, interacts with COA3 and with SMIM20/MITRAC7; the interaction with SMIM20 stabilizes the newly synthesized MT-CO1 and prevents its premature turnover. Interacts with TMEM177 in a COX20-dependent manner (By similarity).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lrrc4c ^@ http://purl.uniprot.org/uniprot/Q8C031 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Highly expressed in the developing cerebral cortex and striatum at 14 dpc.|||Interacts with NTNG1 and WHRN.|||May promote neurite outgrowth of developing thalamic neurons.|||Postsynaptic cell membrane|||The LRR region is both necessary and sufficient for the interaction with NTNG1. http://togogenome.org/gene/10090:Cryzl2 ^@ http://purl.uniprot.org/uniprot/Q3UNZ8 ^@ Similarity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily. http://togogenome.org/gene/10090:Mmgt2 ^@ http://purl.uniprot.org/uniprot/Q8R3L0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the membrane magnesium transporter (TC 1.A.67) family.|||Early endosome membrane|||Golgi apparatus membrane|||High expression levels in brain and kidney with lower levels in heart, colon and liver. Very low levels in intestine. In kidney, highest levels in distal convoluted tubule.|||Mediates Mg(2+) transport.|||Up-regulated by low extracellular Mg(2+). http://togogenome.org/gene/10090:Col18a1 ^@ http://purl.uniprot.org/uniprot/E9QPX1|||http://purl.uniprot.org/uniprot/P39061 ^@ Caution|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the multiplexin collagen family.|||Expressed in liver, kidney, lung, skeletal muscle and testis.|||Forms homotrimers. Recombinant non-collagenous domain 1 has stronger affinity to NID1, HSPG2 and laminin-1:NID1 complex and lower affinity to FBLN1 and FBLN2 than endostatin (PubMed:10966814).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling.|||Monomeric (PubMed:9687493). Interacts with KDR/VEGFR2 (PubMed:12029087). Interacts with the ITGA5:ITGB1 complex (PubMed:11158588). Interacts with NID1, HSPG2, laminin-1:NID1 complex, FBLN1 and FBLN2 (PubMed:10966814, PubMed:11158588, PubMed:12029087).|||Non-collagenous domain 1 seems to be the predominant tissue form from which endostatin is cleaved. However, the proteolytic cleavage site to generate non-collagenous domain 1 is not known. Soluble recombinant non-collagenous domain 1 amenable to biochemical studies has been used instead; its molecular weight corresponds to probable non-collagenous domain 1 immunoblot bands seen in tissue extracts.|||Potently inhibits endothelial cell proliferation and angiogenesis. May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling (PubMed:9008168). Inhibits VEGFA isoform VEGF165-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2 (PubMed:12029087). Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5 (PubMed:11158588). May negatively regulate the activity of homotrimeric non-collagenous domain 1 (By similarity).|||Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) of the triple-helical regions are hydroxylated.|||Secreted|||Undergoes proteolytic processing by CTSL/cathepsin-L and elastase-like proteases to generate both non-collagenous domain 1 trimers and endostatin monomers (PubMed:10716919). In tissue extracts (brain, skeletal muscle, heart, kidney, testis and liver) predominantly bands of approximately 38 kDa are detected; recombinant non-collagenous domain 1 shows similar mobility. In vitro, several proteolytic cleavage sites in the non-collagenous domain 1 hinge region generating different endostatin-like peptides are reported.|||basement membrane|||extracellular matrix http://togogenome.org/gene/10090:Caln1 ^@ http://purl.uniprot.org/uniprot/Q9JJG7 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain-specific. High expression in the cerebellum, hippocampus, and cortex.|||Cell membrane|||Interacts with PI4KB. This binding competes with FREQ/NCS1 binding in a calcium-dependent manner.|||Negatively regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity. May play a role in the physiology of neurons and is potentially important in memory and learning.|||Shows little prenatal expression, with highest expression at postnatal day 21.|||The C-terminal transmembrane domain (TMD) is necessary and sufficient for membrane targeting.|||perinuclear region|||trans-Golgi network membrane http://togogenome.org/gene/10090:Hc ^@ http://purl.uniprot.org/uniprot/P06684 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit ^@ Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled.|||C5 precursor is first processed by the removal of 4 basic residues, forming two chains, beta and alpha, linked by a disulfide bond. C5 convertase activates C5 by cleaving the alpha chain, releasing C5a anaphylatoxin and generating C5b (beta chain + alpha' chain).|||Derived from proteolytic degradation of complement C5, C5a anaphylatoxin is a mediator of local inflammatory process. Binding to the receptor C5AR1 induces a variety of responses including intracellular calcium release, contraction of smooth muscle, increased vascular permeability, and histamine release from mast cells and basophilic leukocytes. C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.|||Interacts with C5AR1.|||Murine C5 deficiency is caused by a 2 base-pairs deletion resulting in frameshift and premature truncation. All C5-deficient strains contain this mutation.|||Secreted http://togogenome.org/gene/10090:Det1 ^@ http://purl.uniprot.org/uniprot/Q9D0A0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DET1 family.|||Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1.|||Component of the E3 ubiquitin ligase DCX DET1-COP1 complex, which is required for ubiquitination and subsequent degradation of target proteins. The complex is involved in JUN ubiquitination and degradation (By similarity).|||Nucleus http://togogenome.org/gene/10090:Irf6 ^@ http://purl.uniprot.org/uniprot/P97431 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IRF family.|||Cytoplasm|||High levels of expression along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin.|||Interacts with SERPINB5.|||Nucleus|||Phosphorylated. Phosphorylation status depends on the cell cycle and is a signal for ubiquitination and proteasome-mediated degradation.|||Probable DNA-binding transcriptional activator. Key determinant of the keratinocyte proliferation-differentiation switch involved in appropriate epidermal development. Plays a role in regulating mammary epithelial cell proliferation. May regulate WDR65 transcription. http://togogenome.org/gene/10090:Tmem184c ^@ http://purl.uniprot.org/uniprot/Q3TPR7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM184 family.|||Membrane|||Possible tumor suppressor which may play a role in cell growth. http://togogenome.org/gene/10090:Clec2g ^@ http://purl.uniprot.org/uniprot/Q9D676 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Constitutively expressed in bone marrow cells. Up-regulated in vagina after 17-beta-estradiol treatment. Down-regulated after removal of ovaries.|||Detected in vagina, eye, tongue, stomach and spleen.|||Inhibits osteoclast formation. http://togogenome.org/gene/10090:Or2l13b ^@ http://purl.uniprot.org/uniprot/Q8VF05 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mbnl2 ^@ http://purl.uniprot.org/uniprot/Q8C181 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the muscleblind family.|||Cytoplasm|||Interacts with ITGA3.|||Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. RNA-binding protein that binds to 5'ACACCC-3' core sequence, termed zipcode, within the 3'UTR of ITGA3. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs. Seems to regulate expression and localization of ITGA3 by transporting it from the nucleus to cytoplasm at adhesion plaques. May play a role in myotonic dystrophy pathophysiology (DM) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Cisd2 ^@ http://purl.uniprot.org/uniprot/Q9CQB5 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CISD protein family. CISD2 subfamily.|||Binds 1 [2Fe-2S] cluster.|||Brain.|||Endoplasmic reticulum membrane|||Expression decreases in an age-dependent manner.|||Homodimer. Interacts with BCL2; the interaction is direct and disrupted by BIK interaction with BCL2. Interacts with BCL2L1. Interacts with ITPR1 (By similarity).|||Mitochondrion outer membrane|||Premature aging associated with a shortened life span, probably caused by mitochondrial degeneration and autophagy. 8 week old mice begin to acquire a set of aged appearance phenomena remarkably similar to those of premature aging syndrome, including prominent eyes and protruding ears. Ocular abnormalities are observed: mice develop opaque eyes and blindness, which is accompanied by cornea damage at 20 week old. The opacity of the cornea is due to debris deposition in the scar tissue outside the cornea. In addition, corneal neovascularization is observed, possibly impairing vision. An early depigmentation in the fur at around 48 week old is also observed; furthermore, hair follicle atrophy and a decreased hair density is detected. A decrease in the hair regrowth rate is also observed. Additionally, the skin of 48-week-old mice exhibits a phenotype with a noticeably thickened dermis, an expanded surface, and a significant decrease in subcutaneous adipose tissue and muscle. The trabeculae of the femur are noticeably thinner and dual energy X-ray absorptiometer (DEXA) detects a decrease in femur density after 8 week old. Mice also display a significant lordokyphosis phenotype after 12 week old; leading to a decrease in mean thoracic volume and thence pulmonary function abnormalities. Muscle degeneration is detectable at 3 week old with a progressive degeneration of muscle fibers and the magnitude of the degeneration exacerbated with age.|||Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy (By similarity). http://togogenome.org/gene/10090:Elp5 ^@ http://purl.uniprot.org/uniprot/Q99L85 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELP5 family.|||Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6; in the complex, is required for optimal binding of ELP3 to ELP4.|||Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (By similarity). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity). Involved in cell migration (PubMed:22854966).|||Cytoplasm|||Nucleus|||The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification.|||Tyrosine-phosphorylated.|||Widely expressed with highest levels in testis (PubMed:9371513). Expressed throughout the cerebellum (PubMed:30097576). http://togogenome.org/gene/10090:Zgrf1 ^@ http://purl.uniprot.org/uniprot/Q0VGT4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Kif3b ^@ http://purl.uniprot.org/uniprot/Q3UHC4|||http://purl.uniprot.org/uniprot/Q61771|||http://purl.uniprot.org/uniprot/Q6P1D3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin II subfamily.|||Deficient mice do not survive beyond midgestation, exhibiting growth retardation, pericardial sac ballooning, and neural tube disorganization (PubMed:9865700). Kif3b +/- mice exhibit schizophrenia-like phenotypes, both behaviorally and histologically. Hippocampal neurons have altered spine morphology and synapse function, and at the cellular level, they display abnormal growth cone morphology (PubMed:31746486).|||Heterodimer of KIF3A and KIF3B (PubMed:7559760). KIF3A/KIF3B heterodimer interacts with KIFAP3 forming a heterotrimeric (KIF3A/KIF3B/KIFAP3) complex (PubMed:8710890). Interacts with the SMC3 subunit of the cohesin complex (By similarity). Interacts directly with IFT20 (PubMed:12821668). Interacts with FLCN (By similarity).|||Microtubule-based molecular motor that transport intracellular cargos, such as vesicles, organelles and protein complexes. Uses ATP hydrolysis to generate force to bind and move along the microtubule (PubMed:7559760). Plays a role in cilia formation (PubMed:9865700). Involved in photoreceptor integrity and opsin trafficking in rod photoreceptors (By similarity). Transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit GRIN2A into neuronal dendrites (PubMed:31746486).|||cilium|||cytoskeleton|||dendritic spine http://togogenome.org/gene/10090:Pabpc1l ^@ http://purl.uniprot.org/uniprot/A2A5N3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the polyadenylate-binding protein type-1 family.|||Binds the poly(A) tail of mRNA.|||Cytoplasm http://togogenome.org/gene/10090:En2 ^@ http://purl.uniprot.org/uniprot/P09066|||http://purl.uniprot.org/uniprot/Q3TZM2 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Engrailed homeobox family.|||Belongs to the engrailed homeobox family.|||Cerebellar granule cells.|||In the adult brain it is found in the cerebellar granule cell layer while the expression during the gestation period is region specific, at the junction of the midbrain and hindbrain.|||Nucleus http://togogenome.org/gene/10090:Plppr2 ^@ http://purl.uniprot.org/uniprot/Q8VCY8 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Has most probably no phospholipid phosphatase activity (By similarity). This is supported by the fact that the phosphatase sequence motifs as well as the His residue acting as a nucleophile in active phosphatases of the PA-phosphatase related phosphoesterase family are not conserved (By similarity).|||Membrane http://togogenome.org/gene/10090:Defb20 ^@ http://purl.uniprot.org/uniprot/Q30KP3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Adm ^@ http://purl.uniprot.org/uniprot/P97297 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ AM and PAMP are potent hypotensive and vasodilatator agents.|||Belongs to the adrenomedullin family.|||Secreted http://togogenome.org/gene/10090:Opn1sw ^@ http://purl.uniprot.org/uniprot/P51491 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Cell membrane|||Expressed in the inner and outer segments of cone photoreceptor cells in the retina (at protein level).|||Knockout mice are viable with normal gross morphology (PubMed:21219924). Cone photoreceptors are normal and provide a normal flash response, however cone cells in the ventral retina have thin or undetectable outer segments that exhibit mild to severe disordered organization (PubMed:21219924, PubMed:25416279). Cone cells show increased sensitivity to mid-wavelength light, potentially as result of increased protein Opn1mw abundance (PubMed:21219924). Lrat and Opn1sw double knockout mice show no change in cone cell viability in the central and ventral retina, however show shorter and swollen outer and inner segments at twelve months of age (PubMed:25416279). Double knockout of Lrat and Opn1sw results in a reduction in the slow degeneration of dorsal cone photoreceptors compared to Lrat knockout mice (PubMed:25416279). Lrat and Opn1sw double knockout mice show a reduced abundance of transmembrane and peripheral membrane-associated proteins in cone inner and outer segments (PubMed:25416279).|||Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.|||Photoreceptor inner segment|||Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal (By similarity). Required for the maintenance of cone outer segment organization in the ventral retina, but not essential for the maintenance of functioning cone photoreceptors (PubMed:21219924, PubMed:25416279). Involved in ensuring correct abundance and localization of retinal membrane proteins (PubMed:25416279). May increase spectral sensitivity in dim light (PubMed:11055434).|||perinuclear region|||photoreceptor outer segment http://togogenome.org/gene/10090:Ang6 ^@ http://purl.uniprot.org/uniprot/Q5GAN0 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Trp53inp2 ^@ http://purl.uniprot.org/uniprot/Q8CFU8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Dual regulator of transcription and autophagy. Positively regulates autophagy and is required for autophagosome formation and processing. May act as a scaffold protein that recruits MAP1LC3A, GABARAP and GABARAPL2 and brings them to the autophagosome membrane by interacting with VMP1 where, in cooperation with the BECN1-PI3-kinase class III complex, they trigger autophagosome development. Acts as a transcriptional activator of THRA.|||Interacts with VMP1, GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B, MAP1LC3C and THRA.|||Nucleus|||PML body|||The LC3 interacting region (LIR) motif mediates interaction with GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C.|||autophagosome|||cytosol http://togogenome.org/gene/10090:Coasy ^@ http://purl.uniprot.org/uniprot/Q9DBL7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bifunctional enzyme that catalyzes the fourth and fifth sequential steps of CoA biosynthetic pathway. The fourth reaction is catalyzed by the phosphopantetheine adenylyltransferase, coded by the coaD domain; the fifth reaction is catalyzed by the dephospho-CoA kinase, coded by the coaE domain. May act as a point of CoA biosynthesis regulation.|||Cytoplasm|||In the central section; belongs to the eukaryotic CoaD family.|||Mitochondrion matrix|||Monomer.|||Widely expressed with highest levels in kidney and lowest levels in colon, lung, intestine, and spleen. http://togogenome.org/gene/10090:Bcl2l1 ^@ http://purl.uniprot.org/uniprot/O35843|||http://purl.uniprot.org/uniprot/Q5HZH3|||http://purl.uniprot.org/uniprot/Q64373 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bcl-X(beta) is expressed in both embryonal and postnatal tissues, whereas Bcl-X(L) is predominantly found in postnatal tissues.|||Belongs to the Bcl-2 family.|||Cytoplasm|||Forms heterodimers with BAX, BAK or BCL2; heterodimerization with BAX does not seem to be required for anti-apoptotic activity (By similarity). Interacts with isoform 1 of SIVA1; the interaction inhibits the anti-apoptotic activity (By similarity). Interacts with IKZF3 (By similarity). Interacts with RTL10/BOP (By similarity). Interacts with DNM1L and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF (By similarity). Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats), but not with NLRP2, NLRP3, NLRP4, PYCARD, nor MEFV (By similarity). Interacts with BECN1 (By similarity).|||Homodimer. Interacts with BAD. Interacts with PGAM5. Interacts with HEBP2. Interacts with p53/TP53 and BBC3; interaction with BBC3 disrupts the interaction with p53/TP53. Interacts with ATP5F1A and ATP5F1B; the interactions mediate the association of isoform Bcl-X(L) with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase (By similarity). Interacts with VDAC1 (By similarity). Interacts with BCL2L11 (via BH3) (PubMed:14499110, PubMed:27013495). Interacts with RNF183 (By similarity). Interacts with GIMAP3/IAN4 and GIMAP5/IAN5 (PubMed:16509771). Interacts with GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and BCL2L1 is impaired in the absence of GIMAP5 (PubMed:21502331). Interacts with isoform 4 of CLU; this interaction releases and activates BAX and promotes cell death (By similarity).|||Isoform Bcl-X(L) also regulates presynaptic plasticity, including neurotransmitter release and recovery, number of axonal mitochondria as well as size and number of synaptic vesicle clusters. During synaptic stimulation, increases ATP availability from mitochondria through regulation of mitochondrial membrane ATP synthase F(1)F(0) activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles (By similarity). May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (By similarity).|||Isoform Bcl-X(S) promotes apoptosis.|||Membrane|||Mitochondrion inner membrane|||Mitochondrion matrix|||Mitochondrion membrane|||Mitochondrion outer membrane|||Nucleus membrane|||Phosphorylated on Ser-62 by CDK1. This phosphorylation is partial in normal mitotic cells, but complete in G2-arrested cells upon DNA-damage, thus promoting subsequent apoptosis probably by triggering caspases-mediated proteolysis. Phosphorylated by PLK3, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Phosphorylation at Ser-49 appears during the S phase and G2, disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during telophase and cytokinesis (By similarity).|||Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.|||Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity.|||The BH4 motif is required for anti-apoptotic activity. The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death.|||The loop between motifs BH4 and BH3 is required for the interaction with NLRP1.|||Ubiquitinated by RNF183 during prolonged ER stress, leading to degradation by the proteosome.|||Widely expressed, with highest levels in the brain, thymus, bone marrow, and kidney. Bcl-X(L) and Bcl-X(delta-TM) expression is enhanced in B- and T-lymphocytes that have been activated.|||centrosome|||cytosol|||synaptic vesicle membrane http://togogenome.org/gene/10090:Pigc ^@ http://purl.uniprot.org/uniprot/Q9CXR4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGC family.|||Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts with PIGQ. Interacts with the heterodimer PIGA:PIGH.|||Endoplasmic reticulum membrane|||Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. http://togogenome.org/gene/10090:Zfat ^@ http://purl.uniprot.org/uniprot/Q7TS63 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in spleen and thymus but not in liver, muscle, heart, kidney, brain, bone marrow or pancreas. Expressed in CD19+, CD4+ and CD8+ lymphocytes but not in CD11b+ lymphocytes or peritoneal macrophages (at protein level).|||May be involved in transcriptional regulation. Overexpression causes down-regulation of a number of genes involved in the immune response. Some genes are also up-regulated.|||Nucleus|||Up-regulated during the transition from CD4-/CD8- to CD4+/CD8+ thymocytes.|||cytosol http://togogenome.org/gene/10090:H3c10 ^@ http://purl.uniprot.org/uniprot/P68433 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (By similarity).|||This histone is only present in mammals.|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Prr23a1 ^@ http://purl.uniprot.org/uniprot/G3UW32 ^@ Similarity ^@ Belongs to the PRR23 family. http://togogenome.org/gene/10090:Gm37013 ^@ http://purl.uniprot.org/uniprot/O88689 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is an head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane (PubMed:27161523). Each cadherin domain binds three calcium ions (PubMed:27161523).|||Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination (Probable). Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain (PubMed:27161523).|||Cell membrane|||Detected in brain throughout embryonic development. Detected in adult brain, in particular in cerebellum and forebrain.|||Forms homodimers in trans (molecules expressed by two different cells) (PubMed:27161523). Forms promiscuous heterodimers in cis (at the plasma membrane of the same cell) with other protocadherins (PubMed:27161523). Interacts with FYN (PubMed:9655502).|||The protocadherins alpha are expressed from a single gene cluster similarly to immunoglobulin and T-cell receptors. The N-terminal region containing the 6 extracellular cadherin domains, unique to each protocadherin alpha, is encoded by one of the large exons found in tandem array within the gene cluster. The C-terminal region, identical to all protocadherins alpha, is encoded by 3 shared exons. http://togogenome.org/gene/10090:Oxa1l ^@ http://purl.uniprot.org/uniprot/Q8BGA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OXA1/ALB3/YidC family.|||Mitochondrion inner membrane|||Monomer; predominantly monomeric at low salt concentrations. Homooligomer; predominantly homooligomeric at high salt concentrations. Homodimer. Homotetramer. Interacts with MRPL13, MRPL20, MRPL28, MRPL48, MRPL49 and MRPL51. Associates preferentially as a dimer with the large ribosomal subunit 39S of the mitochondrial ribosome (By similarity).|||Required for the insertion of integral membrane proteins into the mitochondrial inner membrane. Essential for the activity and assembly of cytochrome oxidase. Required for the correct biogenesis of ATP synthase and complex I in mitochondria (By similarity). http://togogenome.org/gene/10090:Htr5a ^@ http://purl.uniprot.org/uniprot/P30966|||http://purl.uniprot.org/uniprot/Q3UVG4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed predominantly in the central nervous system; in the cerebral cortex, hippocampus, habenula, olfactory bulb and granular layer of the cerebellum.|||Membrane|||This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins. http://togogenome.org/gene/10090:Dcp1a ^@ http://purl.uniprot.org/uniprot/Q91YD3 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DCP1 family.|||Embryonic lethality around embryonic day 10.5 concomitant with massive growth retardation and cardiac developmental defects seen.|||Expression detectable at 9.5 dpc and progressively increases from 11.5 dpc onwards (at protein level).|||Forms a complex with EDC3, DCP2, DDX6 and EDC4/HEDLS, within this complex directly interacts with EDC3. Part of a cytoplasmic complex containing proteins involved in mRNA decay, including XRN1 and LSM1. Interacts with DCP1B. Interacts with DCP2. Interacts with DDX17 in an RNA-independent manner. Interacts with PNRC2. Interacts with SMAD4. Interacts with UPF1. Interacts with ZC3HAV1. Interacts with ZFP36L1. Interacts with NBDY. Interacts with DHX34; the interaction is RNA-independent (By similarity).|||It is uncertain whether Met-1 or Met-21 is the initiator.|||Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP. Contributes to the transactivation of target genes after stimulation by TGFB1 (By similarity). Essential for embryonic development (PubMed:11836524).|||Nucleus|||P-body|||Ubiquitous, with highest expression in the spleen and testis (at protein level). http://togogenome.org/gene/10090:Rab24 ^@ http://purl.uniprot.org/uniprot/P35290 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Isoprenylation is inefficient compared to other Rab family members.|||May be involved in autophagy-related processes.|||Membrane|||The unusual Ser-67, instead of a conserved Gln in other family members, is the cause of low GTPase activity. As a result, the predominant nucleotide associated with the protein is GTP.|||Unlike other Rab family members, does not interact with GDP dissociation inhibitors (GDIs), including ARHGDIA and ARHGDIB.|||Widely expressed, with highest expression in brain.|||cytosol http://togogenome.org/gene/10090:Ttc5 ^@ http://purl.uniprot.org/uniprot/Q99LG4 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cofactor involved in the regulation of various cellular mechanisms such as actin regulation, autophagy, chromatin regulation and DNA repair (PubMed:11511361, PubMed:15448695, PubMed:18451878, PubMed:30420355). In physiological conditions, interacts with cofactor JMY in the cytoplasm which prevents JMY's actin nucleation activity and ability to activate the Arp2/3 complex (PubMed:30420355). Acts as a negative regulator of nutrient stress-induced autophagy by inhibiting JMY's interaction with MAP1LC3B, thereby preventing autophagosome formation (PubMed:30420355). Involves in tubulin autoregulation by promoting its degradation in response to excess soluble tubulin (By similarity). To do so, associates with the active ribosome near the ribosome exit tunnel and with nascent tubulin polypeptides early during their translation, triggering tubulin mRNA-targeted degradation (By similarity). Following DNA damage, phosphorylated by DNA damage responsive protein kinases ATM and CHEK2, leading to its nuclear accumulation and stability (PubMed:15448695, PubMed:18833288). Nuclear TTC5/STRAP promotes the assembly of a stress-responsive p53/TP53 coactivator complex, which includes the coactivators JMY and p300, thereby increasing p53/TP53-dependent transcription and apoptosis (PubMed:11511361). Also recruits arginine methyltransferase PRMT5 to p53/TP53 when DNA is damaged, allowing PRMT5 to methylate p53/TP53 (PubMed:19011621). In DNA stress conditions, also prevents p53/TP53 degradation by E3 ubiquitin ligase MDM2 (PubMed:11511361). Upon heat-shock stress, forms a chromatin-associated complex with heat-shock factor 1 HSF1 and p300/EP300 to stimulate heat-shock-responsive transcription, thereby increasing cell survival (PubMed:18451878). Mitochondrial TTC5/STRAP interacts with ATP synthase subunit beta ATP5F1B which decreased ATP synthase activity and lowers mitochondrial ATP production, thereby regulating cellular respiration and mitochondrial-dependent apoptosis (PubMed:25168243). Mitochondrial TTC5/STRAP also regulates p53/TP53-mediated apoptosis (PubMed:25168243).|||Cytoplasm|||Cytoplasmic vesicle|||Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Interacts with JMY and p300/EP300; the interaction occurs in the nucleus and augments the association between JMY and p300/EP300 in response to DNA damage (PubMed:11511361, PubMed:15448695). Interacts with PRMT5; the interaction is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53 and subsequent methylation (PubMed:19011621). Forms a complex with HSF1 and p300/EP300; these interactions augment chromatin-bound HSF1 and p300/EP300 histone acetyltransferase activity, resulting in enhanced heat-shock-responsive transcription (PubMed:18451878). Interacts with JMY; the interaction occurs in the cytoplasm and results in the inhibition of JYM's nucleation activity (PubMed:30420355). Interacts with ribosome-coding tubulin (via 60S subunit 28S rRNA and protein uL24/RPL26) and the N-terminal of nascent tubulin polypeptide (via alpha-tubulin MREC motif and beta-tubulin MREI motif); these interactions result in tubulin mRNA-targeted degradation (By similarity). Interacts with ATP5F1B; the interaction occurs in the mitochondria and results in ATP production decrease (PubMed:25168243). Interacts with p53/TP53; the interaction occurs in the mitochondria and results in increased apoptosis (PubMed:25168243).|||Mitochondrion matrix|||Nucleus|||Phosphorylation by ATM kinase induces nuclear accumulation while interfering with nuclear export, and phosphorylation by CHEK2 kinase enhances nuclear stability.|||Stress-responsive protein (PubMed:11511361, PubMed:18833288). Induced upon UV or ionizing irradiation (at protein level) (PubMed:11511361). Induced upon heat-shock stress (at protein level) (PubMed:18451878).|||The tetratricopep-repeat (TPR) motifs may function as protein interaction domains. http://togogenome.org/gene/10090:Eif4a1 ^@ http://purl.uniprot.org/uniprot/P60843|||http://purl.uniprot.org/uniprot/Q3TLL6|||http://purl.uniprot.org/uniprot/Q5F2A7 ^@ Domain|||Function|||Similarity|||Subunit ^@ ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.|||Belongs to the DEAD box helicase family. eIF4A subfamily.|||RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.|||eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. Interacts with PAIP1, EIF4E and UPF2. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. May interact with NOM1. Interacts with PDCD4; this interferes with the interaction between EIF4A and EIF4G. Interacts with RBM4 (By similarity). Interacts with DDX3X in an RNA-independent manner (By similarity). http://togogenome.org/gene/10090:Ppp6c ^@ http://purl.uniprot.org/uniprot/Q9CQR6 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PPP phosphatase family. PP-6 (PP-V) subfamily.|||Binds 2 manganese ions per subunit.|||Catalytic subunit of protein phosphatase 6 (PP6) (PubMed:32474700). PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL2 receptor stimulation (By similarity). N-terminal domain restricts G1 to S phase progression in cancer cells, in part through control of cyclin D13 During mitosis, regulates spindle positioning (By similarity). Down-regulates MAP3K7 kinase activation of the IL1 signaling pathway by dephosphorylation of MAP3K7 (By similarity). Acts as a regulator of innate immunity by mediating dephosphorylation CGAS, STING1 and RIGI (PubMed:32474700). Participates also in the innate immune defense against viruses by desphosphorylating RIGI, an essential step that triggers RIGI-mediated signaling activation (By similarity). Also regulates innate immunity by acting as a negative regulator of the cGAS-STING pathway: mediates dephosphorylation and inactivation of CGAS and STING1 (PubMed:32474700). CGAS dephosphorylation at 'Ser-420' impairs its ability to bind GTP, thereby inactivating it (PubMed:32474700).|||Cytoplasm|||Embryonic lethality (PubMed:26868000). Embryos are apparently normal in blastocysts, but degenerate by E7.5 and display clear developmental defects at E8.5, suggesting that mutant embryos die after implantation (PubMed:26868000).|||Mitochondrion|||Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with subunits PPP6R1, PPP6R2 and PPP6R3. Interacts with subunit ANKRD28. Interacts with IGBP1. Interacts with MAP3K7. Interacts with NFKBIE. Interacts with TRIM14 and WRNIP1; these interactions positively regulate the RIG-I signaling pathway.|||Ubiquitously expressed in all tissues tested with strongest expression in lung, spleen, liver, kidney and brain. Weaker expression observed in bladder, pancreas, heart and skeletal muscle. http://togogenome.org/gene/10090:Sun3 ^@ http://purl.uniprot.org/uniprot/Q5SS91 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a probable component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nuclear remodeling during sperm head formation in spermatogenesis. A probable SUN3:SYNE1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette.|||Exclusively expressed in postmeiotic stages of male germ cell development. First detected at day 25 p.p. when spermatids are most frequent within seminiferous tubules.|||Membrane|||Nucleus envelope|||Nucleus inner membrane|||Self-associates. Interacts with SYNE1 and SPAG4/SUN4. Proposed to form a spermatogenesis-specific LINC complex with SYNE1 during sperm head formation possibly implicating a SUN domain-based heterotrimer with SPAG4/SUN4 associating with SYNE1. Can interact with SYNE3; the interaction is questioned by missing colocalization in spermatids.|||Specifically expressed in testis (at protein level). http://togogenome.org/gene/10090:Ccdc91 ^@ http://purl.uniprot.org/uniprot/Q9D8L5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Interacts with GGA1, GGA2 and AP1G1.|||Involved in the regulation of membrane traffic through the trans-Golgi network (TGN). Functions in close cooperation with the GGAs in the sorting of hydrolases to lysosomes.|||Membrane|||trans-Golgi network|||trans-Golgi network membrane http://togogenome.org/gene/10090:H4c1 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Mup8 ^@ http://purl.uniprot.org/uniprot/A2AKN8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Krtap19-9b ^@ http://purl.uniprot.org/uniprot/Q99NG9 ^@ Function|||Induction|||Similarity|||Subunit ^@ Belongs to the KRTAP type 19 family.|||Expression in skin and hair follicle is regulated by HOXC13 and by GATA3.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Gatad2a ^@ http://purl.uniprot.org/uniprot/E9QMN5|||http://purl.uniprot.org/uniprot/Q8CHY6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Both CR1 and CR2 regions are required for speckled nuclear localization.|||Chromosome|||Homooligomer. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Component of the MeCP1 histone deacetylase complex. Interacts with CDK2AP1. Interacts with CHD4. Interacts with ERCC6. Interacts with HDAC1. Interacts with HDAC2. Interacts with MBD2; this interaction is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin. Interacts with MBD3. Interacts with MTA2. Interacts with ZMYND8. Interacts with histone tails, including that of histones H2A, H2B, H3 and H4, the interaction is reduced by histone acetylation.|||Nucleus|||Nucleus speckle|||Transcriptional repressor. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2B. http://togogenome.org/gene/10090:Plxdc1 ^@ http://purl.uniprot.org/uniprot/Q91ZV7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Detected in brain. Highly expressed in Purkinje cells of the cerebellum.|||Expression increases in endothelial cells undergoing capillary morphogenesis.|||Interacts with NID1. May interact with CTTN.|||Plays a critical role in endothelial cell capillary morphogenesis.|||Secreted|||tight junction http://togogenome.org/gene/10090:Taar8a ^@ http://purl.uniprot.org/uniprot/Q5QD07 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Eif1ad ^@ http://purl.uniprot.org/uniprot/Q3THJ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EIF1AD family.|||Interacts with GAPDH and STAT1.|||Nucleus|||Plays a role into cellular response to oxidative stress. Decreases cell proliferation (By similarity). http://togogenome.org/gene/10090:Cdkal1 ^@ http://purl.uniprot.org/uniprot/Q91WE6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the methylthiotransferase family. CDKAL1 subfamily.|||Binds 2 [4Fe-4S] clusters. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||Catalyzes the methylthiolation of N6-threonylcarbamoyladenosine (t(6)A), leading to the formation of 2-methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine.|||Endoplasmic reticulum membrane|||Expressed in pancreas, liver and skeletal muscle, especially in white muscle fibers. http://togogenome.org/gene/10090:3425401B19Rik ^@ http://purl.uniprot.org/uniprot/D3Z1D3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the heart and skeletal muscle (at protein level).|||Interacts with FHL2.|||Plays an important role in cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway.|||Z line http://togogenome.org/gene/10090:Trim43a ^@ http://purl.uniprot.org/uniprot/Q3TL54 ^@ Developmental Stage|||Similarity ^@ Belongs to the TRIM/RBCC family.|||Expression is restricted to preimplantation embryos and peaks at the 8-cell to morula stage. http://togogenome.org/gene/10090:Prex2 ^@ http://purl.uniprot.org/uniprot/Q3LAC4 ^@ Domain|||Function|||Subunit ^@ DH domain alone was unable to confer substrate specificity and recognition.|||Functions as a RAC1 guanine nucleotide exchange factor (GEF), activating Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. Mediates the activation of RAC1 in a PI3K-dependent manner. May be an important mediator of Rac signaling, acting directly downstream of both G protein-coupled receptors and phosphoinositide 3-kinase (By similarity).|||Interacts with RAC1.|||PH domain confers substrate specificity and recognition. Able to discriminate between RAC1, RHOA, and CDC42 (By similarity). http://togogenome.org/gene/10090:Rsbn1 ^@ http://purl.uniprot.org/uniprot/Q80T69 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the round spermatid basic protein 1 family.|||Binds 1 Fe(2+) ion per subunit.|||Expressed abundantly in the testis at 23 days after birth and later. Expressed exclusively in the germ cells.|||Histone demethylase that specifically demethylates dimethylated 'Lys-20' of histone H4 (H4K20me2), thereby modulating chromosome architecture.|||Nucleus|||Phosphorylated by PKA.|||Testis. Expressed exclusively in haploid round spermatids. http://togogenome.org/gene/10090:Ccr4 ^@ http://purl.uniprot.org/uniprot/P51680 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the thymus, macrophages and T- and B-cells.|||High affinity receptor for the C-C type chemokines CCL17/TARC and CCL22/MDC. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Could play a role in lipopolysaccharide (LPS)-induced endotoxic shock. In the CNS, could mediate hippocampal-neuron survival.|||In natural killer cells, CCL22 binding induces phosphorylation on yet undefined Ser/Thr residues, most probably by beta-adrenergic receptor kinases 1 and 2.|||Low expression at 7.5 dpc and 12.5 dpc in the yolk sac. http://togogenome.org/gene/10090:Scamp5 ^@ http://purl.uniprot.org/uniprot/Q9JKD3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCAMP family. SCAMP5 subfamily.|||Brain-specific.|||Cell membrane|||Expressed late in development coincident with the elaboration of mature synapses.|||Golgi apparatus membrane|||Interacts (via C-terminal part) with SYT1 and SYT2; interaction with synaptotagmins making a link with the SNARE molecules. Interacts with SLC9A7 (By similarity).|||Recycling endosome membrane|||Required for the calcium-dependent exocytosis of signal sequence-containing cytokines such as CCL5. Probably acts in cooperation with the SNARE machinery (By similarity).|||synaptic vesicle membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Pcca ^@ http://purl.uniprot.org/uniprot/Q91ZA3 ^@ Cofactor|||Disease Annotation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylated.|||Binds 2 magnesium or manganese ions per subunit.|||Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the transient carboxylation of the biotin covalently attached to the C-terminal biotinyl-binding/biotin carboxyl carrier (BCC) domain.|||Mitochondrion matrix|||Propionic acidemia due to recessively inherited deficiency of PCCase activity often causes life-threatening ketosis and acidosis.|||The biotin cofactor is covalently attached to the C-terminal biotinyl-binding domain and is required for the catalytic activity. Biotinylation is catalyzed by HLCS.|||The holoenzyme is a dodecamer composed of 6 PCCA/alpha subunits and 6 PCCB/beta subunits (By similarity). Interacts (via the biotin carboxylation domain) with SIRT4 (PubMed:23438705). Interacts with SIRT3 and SIRT5 (PubMed:23438705).|||This is one of the 2 subunits of the biotin-dependent propionyl-CoA carboxylase (PCC), a mitochondrial enzyme involved in the catabolism of odd chain fatty acids, branched-chain amino acids isoleucine, threonine, methionine, and valine and other metabolites. Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-CoA/(S)-methylmalonyl-CoA (By similarity). Within the holoenzyme, the alpha subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, while the beta subunit then transfers the carboxyl group from carboxylated biotin to propionyl-CoA (By similarity). Propionyl-CoA carboxylase also significantly acts on butyryl-CoA/butanoyl-CoA, which is converted to ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA (By similarity). Other alternative minor substrates include (2E)-butenoyl-CoA/crotonoyl-CoA (By similarity). http://togogenome.org/gene/10090:Mapk6 ^@ http://purl.uniprot.org/uniprot/Q61532 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation at Ser-189.|||Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Cytoplasm|||Expression increases markedly from days 9 to 11 in the developing embryo, followed by a gradual decrease up to birth.|||Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif) MAPKAPK5. Interacts with UBE3A; this interaction may be indirect and mediated by HERC2, possibly via HERC2 interaction with NEURL4 (By similarity).|||In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.|||Nucleus|||Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.|||Ubiquitination at Met-1 leads to degradation by the proteasome pathway. http://togogenome.org/gene/10090:Cr2 ^@ http://purl.uniprot.org/uniprot/A0A1B0GS59|||http://purl.uniprot.org/uniprot/Q9DC83 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Ceacam1 ^@ http://purl.uniprot.org/uniprot/P31809 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) In case of murine coronavirus (MHV) infection, serves as receptor for MHV S1 spike glycoprotein.|||(Microbial infection) Interacts with MHV S1 spike glycoprotein.|||Apical cell membrane|||Basal cell membrane|||Belongs to the immunoglobulin superfamily. CEA family.|||Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and functions also as an activator during angiogenesis (PubMed:16680193, PubMed:17081782, PubMed:18544705, PubMed:21029969, PubMed:21081647, PubMed:22496641, PubMed:22962327, PubMed:23696226). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors (PubMed:17081782, PubMed:21029969, PubMed:22496641). Plays a role in immune response, of T-cells, natural killer (NK) and neutrophils (PubMed:17081782, PubMed:23696226, PubMed:22496641, PubMed:21029969). Upon TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by blocking granule exocytosis by mediating homophilic binding to adjacent cells, allowing interaction with and phosphorylation by LCK and interaction with the TCR/CD3 complex which recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70 (PubMed:22496641). Also inhibits T-cell proliferation and cytokine production through inhibition of JNK cascade and plays a crucial role in regulating autoimmunity and anti-tumor immunity by inhibiting T-cell through its interaction with HAVCR2 (PubMed:17081782). Upon natural killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-homophilic interactions with CEACAM1 on the target cell and lead to cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation (PubMed:23696226). Upon neutrophils activation negatively regulates IL1B production by recruiting PTPN6 to a SYK-TLR4-CEACAM1 complex, that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (PubMed:22496641). Down-regulates neutrophil production by acting as a coinhibitory receptor for CSF3R by downregulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (PubMed:21029969). Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (PubMed:18544705). Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis. This inernalization promotes interaction with FASN leading to receptor-mediated insulin degradation and to reduction of FASN activity leading to negative regulation of fatty acid synthesis. INSR-mediated phosphorylation also provokes a down-regulation of cell proliferation through SHC1 interaction resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and phosphatidylinositol 3-kinase pathways (By similarity). Functions as activator in angiogenesis by promoting blood vessel remodeling through endothelial cell differentiation and migration and in arteriogenesis by increasing the number of collateral arteries and collateral vessel calibers after ischemia (PubMed:16680193, PubMed:22962327). Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (PubMed:21081647). Down-regulates cell growth in response to EGF through its interaction with SHC1 that mediates interaction with EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (PubMed:15467833). Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (PubMed:19008452). Inhibits cell migration and cell scattering through interaction with FLNA; interfers with the interaction of FLNA with RALA (By similarity). Mediates bile acid transport activity in a phosphorylation dependent manner (By similarity). Negatively regulates osteoclastogenesis (PubMed:25490771).|||Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (PubMed:1633107). Promotes populations of T-cells regulating IgA production and secretion associated with control of the commensal microbiota and resistance to enteropathogens (PubMed:23123061).|||Cell junction|||Cell membrane|||Expressed in granulocytes, lymphocytes, granulocytes, B cells, and T-cells (PubMed:11994468). Expressed in bone. Highly expressed in liver and femur (PubMed:25490771). Highly expressed in neutrophils, and to a lesser extent inmonocytes, and macrophages. Slightly higher expressed in peripheral blood neutrophils (PBNs) (PubMed:21029969). Intestinal T-cells predominantly express isoform 2 while extraintestinal T-cells mainly express isoform 1 (PubMed:23123061). Expressed in small intestine and colon (PubMed:25908210).|||Expression increases during the early stages of osteoblast differentiation, and decreases towards terminal osteoblast differentiation. In addition, expression markedly decreases during the course of osteoclastogenesis.|||Ig-like V-type domain mediates trans-homophilic cell adhesion through homodimerization and this active process is regulated by tyrosine kinase, PTPN11 and PTPN6. Ig-like C2-type and/or cytoplasmic domains mediate cis-dimer/oligomer.|||In intestinal epithelium, up-regulated in the presence of Gram-positive commensal gut bacteria (PubMed:25908210). May also be up-regulated by interferon gamma (IFNG) and TNF (TNF-alpha) (PubMed:25908210). Isoform 2: Expression is promoted and maintained by the mucosal environment (PubMed:23123061). Induced by IL2 on natural killer cell (PubMed:23696226).|||Knockout mice exhibit impairment of insulin clearance and hyperinsulinemia, which cause insulin resistance; develop insulin resistance primarily in liver (PubMed:18544705). Display normal white blood cell, red blood cell, hemoglobin and platelet. On the other hand, mice have a high number of neutrophils. Display also increased thrombus growth, and enhanced susceptibility to type I collagen induced pulmonary thromboembolism (PubMed:19008452). Spontaneously develop systemic neutrophilia. Upon Listeria Monocytogenes (LM) infection mice die dramatically faster within 7 days and display an improved bacterial clearance accompanied by severe tissue damage and necrosis in the liver (PubMed:21029969). Knockout mice present an increased basal permeability (PubMed:21081647). Knockout mice show a reduced bone mass namely a decreased trabecular bone volume accompanied by a reduction in trabecular number and an increase in trabecular separation (PubMed:25490771).|||Lateral cell membrane|||Monomer. Oligomer. Heterodimer. Homodimer (By similarity). Cis-dimer/oligomer (via Ig-like C2-type and/or via cytoplasmic domains); induced by trans-homophilic cell adhesion through an allosteric mechanism transmitted by the Ig-like V-type domain, and is regulated by intracellular calcium and calmodulin. Interacts (via cytoplasmic domain) with calmodulin in a calcium dependent manner; reduces homophilic cell adhesion through dissociation of dimer (By similarity). Isoform 1 interacts (via cytoplasmic domain) with PTPN11 (preferentially) and PTPN6; cis-homodimer form is preferred; this interaction is decreased by formation of isoform 1 / isoform 2 cis-heterodimers and is dependent on the monomer/dimer equilibrium; this interaction is phosphorylation-dependent (PubMed:9867848). Isoform 1 interacts with LYN (PubMed:22496641). Isoform 1 interacts (via cytoplasmic domain) with SRC (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion (By similarity). Isoform 1 interacts with LCK; mediates phosphorylation at Tyr-488 and Tyr-515 resulting in PTPN6 association. Isoform 1 interacts with PTPN6; this interaction is phosphorylation-dependent and causes a profound decrease in TCR stimulation-induced CD247 and ZAP70 phosphorylation. Isoform 1 interacts with TCR/CD3 complex through TCR beta chain and CD3E; colocalizes at the cell surface and upon stimulation of the TCR/CD3 complex recruits PTPN6 in the TCR/CD3 complex, resulting in dephosphorylation of CD247 and ZAP70 (By similarity). Isoform 1 interacts (via cytoplasmic domain) with SHC1 (via SH2 domain); SHC1 mediates interaction with INSR or EGFR in a Ser-503 phosphorylation-dependent manner (PubMed:15467833). Isoform 1 interacts with EGFR; the interaction is indirect (By similarity). Isoform 1 interacts with CSF3R; down-regulates the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (PubMed:21029969). Isoform 1 (phosphorylated form) interacts with TLR4 and SYK; recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity (PubMed:22496641). Isoform 1 interacts with FLNA; inhibits cell migration and cell scattering by interfering with the interaction of FLNA with RALA. Isoform 1 interacts (via cytoplasmic domain) with PXN; the interaction is phosphotyrosyl-dependent. Isoform 1 interacts with KLRK1; recruits PTPN6 that dephosphorylates VAV1. Isoform 1 interacts with CEACAM8 (By similarity). Isoform 1 interacts with FASN; this interaction is insulin and phosphorylation-dependent; reduces fatty-acid synthase activity (By similarity). Interacts (via Ig-like V-type) with HAVCR2 (via Ig-like V-type); facilitates the maturation and cell surface expression of HAVCR2 thereby regulating T-cell tolerance induction (By similarity) (PubMed:25363763). Isoform 2 interacts (via the cytoplasmic domain) with ANXA2; this interaction is regulated by phosphorylation and appears in the AIIt complex. Interacts (via Lewis X moieties) with CD209 (via C-type lectin domain); this interaction is regulated by the glycosylation pattern of CEACAM1 on cell types and regulates contact between dendritic cells and neutrophils (By similarity).|||Phosphorylated on serine and threonine.|||Phosphorylated on serine and tyrosine (By similarity). Isoform 1 is phosphorylated on tyrosine by Src family kinases like SRC and LCK and by receptor like CSF3R, EGFR and INSR upon stimulation (PubMed:9867848, PubMed:21029969). Phosphorylated at Ser-503; mediates activity. Phosphorylated at Tyr-488; regulates activity (By similarity). Phosphorylated at Tyr-488 by EGFR and INSR upon stimulation; this phosphorylation is Ser-503-phosphorylation-dependent; mediates cellular internalization; increases interaction with FASN (By similarity). Phosphorylated at Tyr-488 and Tyr-515 by LCK; mediates PTPN6 association and is regulated by homophilic ligation of CEACAM1 in the absence of T-cell activation (By similarity). Phosphorylated at Tyr-515; mediates interaction with PTPN11 (PubMed:9867848).|||adherens junction|||microvillus membrane|||secretory vesicle http://togogenome.org/gene/10090:Slc6a1 ^@ http://purl.uniprot.org/uniprot/P31648|||http://purl.uniprot.org/uniprot/Q6PCX2 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A1 subfamily.|||Brain. Expressed in the dentate gyrus of hippocampus, striatum and cerebellum (at protein level).|||Cell membrane|||Inhibited by N-[4,4-Diphenyl-3-butenyl]-nipecotic acid (SKF-89976-A), L-2,4-diamino-n-butyric acid, guvacine and nipecotic acid.|||Interacts (via PDZ domain-binding motif) with PALS1; interaction increases SLC6A1-mediated GABA uptake.|||Mediates transport of gamma-aminobutyric acid (GABA) together with sodium and chloride and is responsible for the reuptake of GABA from the synapse (PubMed:15234345, PubMed:16150932, PubMed:8420981, PubMed:30270321). The translocation of GABA, however, may also occur in the reverse direction leading to the release of GABA (By similarity). The direction and magnitude of GABA transport is a consequence of the prevailing thermodynamic conditions, determined by membrane potential and the intracellular and extracellular concentrations of Na(+), Cl(-) and GABA (By similarity). Can also mediate sodium- and chloride-dependent transport of hypotaurine but to a much lower extent as compared to GABA (PubMed:30270321).|||Membrane|||Presynapse|||This protein is the target of psychomotor stimulants such as amphetamines or cocaine. http://togogenome.org/gene/10090:Casp14 ^@ http://purl.uniprot.org/uniprot/O89094|||http://purl.uniprot.org/uniprot/Q542Q1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C14A family.|||Cytoplasm|||Embryo, adult liver and less in adult brain and kidney. Expressed in differentiating keratinocytes of embryonic skin (at protein level). Expressed in keratinocytes of adult skin suprabasal layers (at protein level).|||Expressed at embryonic day 18 specifically in cornified epithelium in the suprabasal layers.|||Heterodimer of a large and a small subunit, both processed from the precursor; the mature active form is a p17/p10 dimer and the intermediate form a p20/p8 dimer.|||Maturation by proteolytic processing appears to be a two-step process. The precursor is processed by KLK7 to yield the p20/p8 intermediate form which acts the precursor to yield the p17/p10 mature form (By similarity). Initially it was reported that cleavage by granzyme B, caspase-8 and -10 generates the two active subunits, however the physiological relevance has not been established (PubMed:9823333).|||Mice show a shiny and lichenified skin with an epidermis containing more alveolar keratohyalin F-granules and an altered profilaggrin processing. The skin is highly sensitive to the formation of cyclobutane pyrimidine dimers after UVB irradiation, leading to increased levels of UVB-induced apoptosis (PubMed:17515931). Mice accumulate incomplete filaggrin breakdown products within the epidermal stratum corneum (SC), leading to reduced levels of natural moisturizing factors (NMFs) and lower SC hydration (PubMed:21654840).|||Non-apoptotic caspase which is involved in epidermal differentiation. Seems to play a role in keratinocyte differentiation and is required for cornification (PubMed:18156206). Regulates maturation of the epidermis by proteolytically processing filaggrin (PubMed:21654840). In vitro is equally active on the synthetic caspase substrates WEHD-ACF and IETD-AFC. Involved in processing of prosaposin in the epidermis (PubMed:24872419). May be involved in retinal pigment epithelium cell barrier function (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fndc10 ^@ http://purl.uniprot.org/uniprot/A2A9Q0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cep126 ^@ http://purl.uniprot.org/uniprot/Q0VBV7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with DCTN1 (By similarity).|||Midbody|||Participate in cytokinesis (By similarity). Necessary for microtubules and mitotic spindle organization (By similarity). Involved in primary cilium formation (By similarity).|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Scmh1 ^@ http://purl.uniprot.org/uniprot/Q8K214 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with Polycomb group (PcG) multiprotein complexes; the complex class is required to maintain the transcriptionally repressive state of some genes.|||Associates with a PRC1-like complex (By similarity). Interacts with the SAM domain of PHC1 via its SAM domain in vitro.|||Belongs to the SCM family.|||By retinoic acid in F9 and F19 embryonal carcinoma cell lines.|||Detected throughout embryogenesis. Expressed ubiquitously in 8.5 dpc embryos. At 10.5 dpc, strongly expressed in nervous system including hindbrain and spinal cord, and in the pharyngeal arches and visceral organs. By 14.5 dpc, strong expression is detected throughout the central nervous system, and in tongue, heart, midgut and urogenital regions.|||Most abundant in testis. Moderate levels detected in heart, brain, lung, liver, skeletal muscle and kidney and lower levels in spleen.|||Nucleus http://togogenome.org/gene/10090:Gadd45g ^@ http://purl.uniprot.org/uniprot/Q9R0S0 ^@ Similarity ^@ Belongs to the GADD45 family. http://togogenome.org/gene/10090:Or6c216 ^@ http://purl.uniprot.org/uniprot/Q8VG64 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grm3 ^@ http://purl.uniprot.org/uniprot/Q9QYS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.|||Interacts with TAMALIN. http://togogenome.org/gene/10090:Wfdc15a ^@ http://purl.uniprot.org/uniprot/Q8BH89 ^@ Function|||Subcellular Location Annotation ^@ Antibacterial protein.|||Secreted http://togogenome.org/gene/10090:Podxl2 ^@ http://purl.uniprot.org/uniprot/D3YW47|||http://purl.uniprot.org/uniprot/G3X9D3|||http://purl.uniprot.org/uniprot/Q8CAE9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a ligand for vascular selectins. Mediates rapid rolling of leukocytes over vascular surfaces through high affinity divalent cation-dependent interactions with E-, P- and L-selectins.|||Belongs to the podocalyxin family.|||Glycosylated; contains chondroitin sulfate. Displays sialylated O-linked oligosaccharides.|||Homodimer; disulfide-linked. Interacts with SELL, SELE and SELP.|||Membrane|||Sulfation is necessary for interaction with SELL. Sialylated O-linked oligosaccharides are necessary for interaction with SELL, SELE and SELP. http://togogenome.org/gene/10090:Macrod1 ^@ http://purl.uniprot.org/uniprot/Q922B1 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with ESR1; Interacts in a manner that is estrogen independent but is enhanced by estrogen. Interacts (via macro domain) with AR.|||Nucleus|||Removes ADP-ribose from aspartate and glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.|||Subject to competitive inhibition by the product ADP-ribose. http://togogenome.org/gene/10090:Vamp2 ^@ http://purl.uniprot.org/uniprot/P63044|||http://purl.uniprot.org/uniprot/Q8CHR4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type B (BoNT/B, botB); 20 hours after treatment of spinal cord cells almost all the protein has been digested (PubMed:10413679). BoNT/B hydrolyzes the 76-Gln-|-Phe-77 bond and inhibits neurotransmitter release (Probable).|||(Microbial infection) Targeted and hydrolyzed by C.tetani toxin (tetX); 20 hours after treatment of spinal cord cells almost all the protein has been digested (PubMed:10413679). Tetanus toxin hydrolyzes the 76-Gln-|-Phe-77 bond and inhibits neurotransmitter release (Probable).|||Belongs to the synaptobrevin family.|||Cell membrane|||Expressed in the outer plexiform layer of the retina (at protein level).|||Involved in the targeting and/or fusion of transport vesicles to their target membrane (PubMed:9430681). Major SNARE protein of synaptic vesicles which mediates fusion of synaptic vesicles to release neurotransmitters. Essential for fast vesicular exocytosis and activity-dependent neurotransmitter release as well as fast endocytosis that mediates rapid reuse of synaptic vesicles (PubMed:15475946). Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (By similarity).|||Membrane|||Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A; this complex constitutes the basic catalytic machinery of the complex neurotransmitter release apparatus (PubMed:19196426, PubMed:28821673). Recruited to the SNARE complex following binding of the SNARE complex component STX1A to STXBP1 (PubMed:28821673). This complex binds to CPLX1. Interacts with VAPA and VAPB (By similarity). Interacts (via N-terminus) with KCNB1 (via N-terminus and C-terminus); stimulates the channel inactivation rate of KCNB1 (By similarity). Interacts with BVES and STX4. Interacts with WDFY2, PRKCZ and PRKCI (PubMed:17313651). Forms a complex with WDFY2 and PRKCZ (PubMed:17313651). Interacts with SEPT8; the interaction inhibits interaction of VAMP2 with SYP (PubMed:19196426). Interacts with SYP; the interaction is inhibited by interaction with SEPT8 (PubMed:19196426). Interacts with PICALM (By similarity). Interacts with alpha-synuclein/SNCA. Interacts with STX3 isoform 3B (PubMed:26406599).|||Phosphorylated by PRKCZ in vitro and this phosphorylation is increased in the presence of WDFY2.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Igsf6 ^@ http://purl.uniprot.org/uniprot/P0C6B7 ^@ Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Membrane|||This gene is coded entirely within the intron of Mettl9 which is transcribed in the opposite strand of the DNA.|||Ubiquitous with higher expression in immune tissue. http://togogenome.org/gene/10090:Il1a ^@ http://purl.uniprot.org/uniprot/P01582|||http://purl.uniprot.org/uniprot/Q3U0Y6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated within its nuclear localization sequence, which impacts subcellular localization.|||Belongs to the IL-1 family.|||Cytokine constitutively present intracellularly in nearly all resting non-hematopoietic cells that plays an important role in inflammation and bridges the innate and adaptive immune systems (PubMed:16256210). After binding to its receptor IL1R1 together with its accessory protein IL1RAP, forms the high affinity interleukin-1 receptor complex. Signaling involves the recruitment of adapter molecules such as MYD88, IRAK1 or IRAK4. In turn, mediates the activation of NF-kappa-B and the three MAPK pathways p38, p42/p44 and JNK pathways (PubMed:1386364). Within the cell, acts as an alarmin and cell death results in its liberation in the extracellular space after disruption of the cell membrane to induce inflammation and alert the host to injury or damage. In addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, directly senses DNA damage and acts as signal for genotoxic stress without loss of cell integrity (By similarity).|||Cytoplasm|||Deletion mice show reduced nociceptive sensitivity compared to control mice in models of inflammatory and nerve injury-induced pain when associated with IL1B deletion.|||Monomer.|||Monomer. Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion. Interacts with IL1R1. Interacts with S100A13; this interaction is the first step in the export of IL1A, followed by direct translocation of this complex across the plasma membrane.|||Nucleus|||Phosphorylated. Phosphorylation greatly enhances susceptibility to digestion and promotes the conversion of pre-IL1A alpha to the biologically active IL1A.|||Proteolytic processed by CAPN1 in a calcium-dependent manner. Cleavage from 31 kDa precursor to 18 kDa biologically active molecules.|||Secreted|||The similarity among the IL-1 precursors suggests that the amino ends of these proteins serve some as yet undefined function. http://togogenome.org/gene/10090:Acer2 ^@ http://purl.uniprot.org/uniprot/Q8VD53 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alkaline ceramidase family.|||Chimera.|||Golgi apparatus membrane|||Golgi ceramidase that catalyzes the hydrolysis of ceramides into sphingoid bases like sphingosine and free fatty acids at alkaline pH (PubMed:29401619). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:29401619). Has a better catalytic efficiency towards unsaturated long-chain ceramides, including C18:1-, C20:1- and C24:1-ceramides (By similarity) (PubMed:29401619). Saturated long-chain ceramides and unsaturated very long-chain ceramides are also good substrates, whereas saturated very long-chain ceramides and short-chain ceramides are poor substrates. Also hydrolyzes dihydroceramides to produce dihydrosphingosine (By similarity). It is the ceramidase that controls the levels of circulating sphingosine-1-phosphate and dihydrosphingosine-1-phosphate in plasma through their production by hematopoietic cells (PubMed:29401619). Regulates cell proliferation, autophagy and apoptosis by the production of sphingosine and sphingosine-1-phosphate. As part of a p53/TP53-dependent pathway, promotes for instance autophagy and apoptosis in response to DNA damage. Through the production of sphingosine, may also regulate the function of the Golgi complex and regulate the glycosylation of proteins (By similarity).|||Homozygous knockout mice display no overt phenotype (PubMed:29401619). Reduced levels of sphingosine, dihydrosphingosine, sphingosine-1-phosphate and dihydrosphingosine -1-phosphate are observed in plasma, erythrocytes and platelets (PubMed:29401619).|||Widely expressed with higher expression in lung. http://togogenome.org/gene/10090:Eif4a2 ^@ http://purl.uniprot.org/uniprot/E9Q561|||http://purl.uniprot.org/uniprot/P10630|||http://purl.uniprot.org/uniprot/Q52KC1|||http://purl.uniprot.org/uniprot/Q8BTU6 ^@ Domain|||Function|||Similarity|||Subunit ^@ ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon.|||Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. eIF4A subfamily.|||RNA helicase.|||The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.|||eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIFFG3. Interacts with EIF4E. May interact with NOM1 (By similarity). http://togogenome.org/gene/10090:Gsta1 ^@ http://purl.uniprot.org/uniprot/P13745 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Alpha family.|||Expressed in the liver, skin and kidney.|||Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (PubMed:9606968). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis. Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid (By similarity).|||Homodimer.|||Induced in the liver by beta-naphthoflavone (BNF) and 2(3)-t-butyl-4-hydroxyanisole (BHA). http://togogenome.org/gene/10090:Irx6 ^@ http://purl.uniprot.org/uniprot/Q8BFT1|||http://purl.uniprot.org/uniprot/Q9ER75 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TALE/IRO homeobox family.|||Expressed in a subset of retinal ganglion cells and bipolar cells; including in type 2 and type 3a bipolar cells.|||Expressed in heart, neural tube, limb buds and developing eye (PubMed:11335133). Earliest expression at embryonic 10.5 dpc in the heart, restricted to the endocardium that lines the atrial and ventricular myocardium (PubMed:11335133). Expressed in neural tube at 11.5-12.5 dpc, especially in the ventral regions, most likely in the motor neurons (PubMed:11335133). Expressed in fore and hindlimbs at 10.5-13.5 dpc (PubMed:11335133). Also expressed in area lining the lumen of the otic vesicle at 12 dpc and in the mammary gland primordium at 13.5 dpc (PubMed:11335133). Expressed in the marginal zone of the neural layer, and the central ganglion cell region, of the retina at 13.5 dpc (PubMed:11335133, PubMed:23172916). By 16.5 dpc, expressed in the developing retinal ganglion cell layer and optic nerve region; at postnatal day zero (P0), expression persists in the ganglion cell layer, and in the apical margin region of the retina (PubMed:23172916). By P7, expressed in a number of cells within the outer half of the inner nuclear layer and in the ganglion cell layer (PubMed:23172916). Transiently expressed in newly born photoreceptor cells at P0, but not in adult photoreceptor cells (PubMed:23172916).|||Nucleus|||Transcription factor (PubMed:23172916). Binds to the iroquois binding site (IBS) motif of target genes to regulate gene expression; functions as a transcriptional activator or repressor (PubMed:23172916). Modulates expression of RCVRN, VSX1, BHLHE22/BHLHB5 and TACR3/Nk3r (PubMed:23172916). Required downstream of retinal bipolar cell specification for the terminal differentiation of type 2, type 3a and possibly type 6 bipolar cells (PubMed:23172916). http://togogenome.org/gene/10090:Samm50 ^@ http://purl.uniprot.org/uniprot/Q8BGH2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with parasite T.gondii RH strain MAF1b1; the interaction is probably indirect and results in the disruption of the MIB complex and the formation of SPOTs (structures positive for outer mitochondrial membrane (OMM)), a cellular response to OMM stress, which leads to the constitutive shedding of OMM vesicles.|||Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex (By similarity). The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9 (By similarity). The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex (By similarity). Interacts with IMMT/MIC60 (By similarity). Interacts with CHCHD3/MIC19 (PubMed:21081504). Interacts with ARMC1 (By similarity).|||Belongs to the SAM50/omp85 family.|||Cytoplasm|||Its C-terminal part seems to contain many membrane-spanning sided beta-sheets, that have the potential to adopt a transmembrane beta-barrel type structure.|||Mitochondrion|||Mitochondrion outer membrane|||Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes. Required for the assembly of TOMM40 into the TOM complex. http://togogenome.org/gene/10090:Atp2b4 ^@ http://purl.uniprot.org/uniprot/D1FNM8|||http://purl.uniprot.org/uniprot/D1FNM9|||http://purl.uniprot.org/uniprot/E9Q828|||http://purl.uniprot.org/uniprot/F7AAP4|||http://purl.uniprot.org/uniprot/Q3UPA8|||http://purl.uniprot.org/uniprot/Q6Q477 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by calcium/calmodulin.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.|||Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell (By similarity). By regulating sperm cell calcium homeostasis, may play a role in sperm motility (PubMed:15078889).|||Catalyzes the hydrolysis of ATP coupled with the transport of calcium.|||Interacts with PDZD11. Interacts with SLC35G1 and STIM1. Interacts with calmodulin.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Male mice lacking Atp2b4 are infertile with severe reduction of sperm motility.|||Membrane|||Specifically expressed by sperm in testis (at protein level).|||flagellum membrane http://togogenome.org/gene/10090:Cul4a ^@ http://purl.uniprot.org/uniprot/Q3TCH7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ (Microbial infection) Deneddylated by murine cytomegalovirus M48 leading to a S-phase-like environment that is required for efficient replication of the viral genome.|||(Microbial infection) Interacts with murine cytomegalovirus M48.|||Belongs to the cullin family.|||Can self-associate. Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1. Component of the DCX(DDB2) complex with the substrate recognition component DDB2. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Component of DCX complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either TRPC4AP or DCAF12 as substrate-recognition component. Component of the DCX(AMBRA1) complex with the substrate recognition component AMBRA1. Interacts with DDB1, RBX1, RNF7, CDT1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive. Interacts with DCAF1, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, COP1, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5, LRWD1 and DCAF8. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. The DDB1-CUL4A complex interacts with CRY1. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation.|||Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of p53/TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(DTL) directs autoubiquitination of DTL. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1. A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. With CUL4B, contributes to ribosome biogenesis. The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes.|||Expressed at high levels in germinal vesicle (GV) stage oocytes and at lower levels in MII-stage oocytes and zygotes. Expression then decreases from 4-cell stage to blastula.|||Expressed in oocytes (at protein level) (PubMed:24357321). In the ovary, also expressed in cumulus cells. Expressed in testis, spleen and kidney (PubMed:24357321).|||Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. http://togogenome.org/gene/10090:Rab39b ^@ http://purl.uniprot.org/uniprot/Q0PD14|||http://purl.uniprot.org/uniprot/Q8BHC1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Golgi apparatus|||Interacts (in GTP-bound form) with PICK1 (via PDZ domain); a PICK1 homodimer may allow simultaneous association of RAB39B and GRIA2 to PICK1 which is involved in GRIA2 trafficking. Interacts with isoform c of RASSF1; the interaction is strong (PubMed:23294242). Interacts with isoform a of RASSF1; the interaction is weak (PubMed:23294242). Interacts with the DLG4/PSD-95 (PubMed:31651360).|||Membrane|||Small GTPases Rab involved in autophagy. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). May be involved in vesicular trafficking (PubMed:20159109). Plays a role in synapse formation. May regulate the homeostasis of SNCA/alpha-synuclein (PubMed:25434005). Together with PICK1 proposed to ensure selectively GRIA2 exit from the endoplasmic reticulum to the Golgi and to regulate AMPAR compostion at the post-synapses and thus synaptic transmission (PubMed:25784538).|||Specifically expressed in neuron and neuronal precursors in the brain. Expression is high in all regions of the brain with highest levels observed in the hippocampus. http://togogenome.org/gene/10090:Nms ^@ http://purl.uniprot.org/uniprot/A0A250SH12|||http://purl.uniprot.org/uniprot/Q5H8A1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NmU family.|||Implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.|||Secreted http://togogenome.org/gene/10090:Ddx21 ^@ http://purl.uniprot.org/uniprot/Q6PCP0|||http://purl.uniprot.org/uniprot/Q9JIK5 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation by CREBBP/CBP inhibits the helicase activity. Deacetylation by SIRT7 promotes the helicase activity and overcomes R-loop-mediated stalling of RNA polymerases.|||Acetylation inhibits the helicase activity.|||Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.|||Highly expressed in liver and testis. Expressed at lower level in brain, lungs, and skeletal muscle.|||Homodimer; homodimerizes via its N-terminus (PubMed:21703541). Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation (PubMed:21703541). Interacts (via C-terminus) with TICAM1 (via TIR domain) (PubMed:21703541). Interacts with DHX36 (via C-terminus); this interaction serves as bridges to TICAM1 (PubMed:21703541). Interacts (via C-terminus) with DDX1 (via B30.2/SPRY domain); this interaction serves as bridges to TICAM1 (PubMed:21703541). Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Interacts with C1QBP. Interacts with JUN. Interacts with WDR46. Interacts with MCM3AP (By similarity). Interacts with WDR43 (PubMed:31128943). Interacts with KPNA3 (By similarity).|||Mitochondrion|||RNA helicase that acts as a sensor of the transcriptional status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA (rRNA) processing and transcription from polymerase II (Pol II) (By similarity). Binds various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs (By similarity). In the nucleolus, localizes to rDNA locus, where it directly binds rRNAs and snoRNAs, and promotes rRNA transcription, processing and modification (By similarity). Required for rRNA 2'-O-methylation, possibly by promoting the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-ribosomal complexes (By similarity). In the nucleoplasm, binds 7SK RNA and is recruited to the promoters of Pol II-transcribed genes: acts by facilitating the release of P-TEFb from inhibitory 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes (By similarity). Functions as cofactor for JUN-activated transcription: required for phosphorylation of JUN at 'Ser-77' (By similarity). Can unwind double-stranded RNA (helicase) and can fold or introduce a secondary structure to a single-stranded RNA (foldase) (By similarity). Together with SIRT7, required to prevent R-loop-associated DNA damage and transcription-associated genomic instability: deacetylation by SIRT7 activates the helicase activity, thereby overcoming R-loop-mediated stalling of RNA polymerases (By similarity). Involved in rRNA processing. May bind to specific miRNA hairpins (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (PubMed:21703541).|||The 3 X 5 AA repeats seem to be critical for the RNA folding activity.|||The helicase and foldase activities reside in two separate domains, the helicase in the N-terminus and the foldase in the C-terminus.|||cytosol|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Ssbp2 ^@ http://purl.uniprot.org/uniprot/Q540I3|||http://purl.uniprot.org/uniprot/Q9CYZ8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Akap8l ^@ http://purl.uniprot.org/uniprot/Q5RL57|||http://purl.uniprot.org/uniprot/Q9D0K8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the AKAP95 family.|||Nucleus matrix http://togogenome.org/gene/10090:Casd1 ^@ http://purl.uniprot.org/uniprot/Q7TN73 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PC-esterase family. CASD1 subfamily.|||Expressed in neonatal brain and in day 10 and 13 embryo.|||Golgi apparatus membrane|||N-glycosylated.|||O-acetyltransferase that catalyzes 9-O-acetylation of sialic acids. Sialic acids are sugars at the reducing end of glycoproteins and glycolipids, and are involved in various processes such as cell-cell interactions, host-pathogen recognition.|||The Casd1 locus is imprinted. Maternal inherited gene is expressed, while the paternal inherited gene is silenced.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Nherf4 ^@ http://purl.uniprot.org/uniprot/Q99MJ6 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation (By similarity). Stimulates SLC9A3 activity in the presence of elevated calcium ions (By similarity).|||Cell membrane|||Cytoplasm|||Expressed in kidney and small intestine. Not detected in heart, brain, spleen, lung, liver, skeletal muscle or testis.|||Interacts with the C-terminal region of GUCY2C (By similarity). Interacts with C-terminal region of SLC9A3 and the interactions decrease in response to elevated calcium ion levels (By similarity). Interacts with the C-terminal region of SLC34A1 (PubMed:11099500). Interacts with USP2 isoform 2 (PubMed:26756164). Interacts (via the third PDZ domain) with SLC26A3 (via PDZ-binding motif) (PubMed:22627094). This interaction leads to decreased expression of SLC26A3 on the cell membrane resulting in its reduced exchanger activity (By similarity).|||Isoform 2: Expressed in a circadian manner in the intestine.|||Phosphorylation at Ser-329 negatively regulates its interaction with SLC26A3. http://togogenome.org/gene/10090:Pyy ^@ http://purl.uniprot.org/uniprot/H3BK86|||http://purl.uniprot.org/uniprot/Q3V334|||http://purl.uniprot.org/uniprot/Q9EPS2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NPY family.|||Secreted|||The peptide YY form is cleaved at Pro-30 by the prolyl endopeptidase FAP (seprase) activity (in vitro) to generate peptide YY(3-36).|||This gut peptide inhibits exocrine pancreatic secretion, has a vasoconstrictory action and inhibitis jejunal and colonic mobility. http://togogenome.org/gene/10090:Sync ^@ http://purl.uniprot.org/uniprot/Q9EPM5 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical type III intermediate filament (IF) protein that may play a supportive role in the efficient coupling of mechanical stress between the myofibril and fiber exterior. May facilitate lateral force transmission during skeletal muscle contraction. Does not form homofilaments nor heterofilaments with other IF proteins.|||Belongs to the intermediate filament family.|||Detected strongly in skeletal muscle and heart and weakly in lung (at protein level). Highly expressed in skeletal muscle and lung and weakly in lung and testis.|||Displays no obvious abnormalities, have a reduced capacity to generate force during isometric contractions in skeletal muscle.|||May link the dystrophin-associated glycoprotein complex (DAPC) to intracellular desmin (DES) filaments. Interacts with DES and DTNA.|||Up-regulated in dystrophic muscle (at protein level).|||perinuclear region http://togogenome.org/gene/10090:Metrn ^@ http://purl.uniprot.org/uniprot/Q8C1Q4 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the meteorin family.|||By all-trans retinoic acid (ATRA).|||Highly expressed in brain. Expressed in undifferentiated neural progenitors and in astrocyte lineage, particulary in Bergmann glia, a subtype of radial glia, and a few discrete neuronal populations residing in the superior colliculus, the ocular motor nucleus, the raphe and pontine nuclei, and in various thalamic nuclei. Weakly expressed in heart, kidney, skeletal muscle, spleen, testis, gut and lung.|||Involved in both glial cell differentiation and axonal network formation during neurogenesis. Promotes astrocyte differentiation and transforms cerebellar astrocytes into radial glia. Also induces axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia.|||Monomer.|||Secreted|||Was called meteorin because it can transform glial cells into cells with an elongated trail. http://togogenome.org/gene/10090:Il1r1 ^@ http://purl.uniprot.org/uniprot/P13504|||http://purl.uniprot.org/uniprot/Q32MH0|||http://purl.uniprot.org/uniprot/Q8C6P3|||http://purl.uniprot.org/uniprot/Q8C833 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble form (sIL1R1) is probably produced by proteolytic cleavage at the cell surface (shedding).|||Belongs to the interleukin-1 receptor family.|||Cell membrane|||Isoform 2 is expressed in various brain tissues.|||Membrane|||Rapidly phosphorylated on Tyr-499 in response to IL-1, which creates a SH2 binding site for the PI 3-kinase regulatory subunit PIK3R1.|||Receptor for IL1A, IL1B and IL1RN. After binding to interleukin-1 associates with the coreceptor IL1RAP to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B, MAPK and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Binds ligands with comparable affinity and binding of antagonist IL1RN prevents association with IL1RAP to form a signaling complex. Involved in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells (By similarity).|||Secreted|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.|||The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Interacts with PIK3R1. Interacts with IL1A (By similarity).|||Unable to mediate canonical IL-1 signaling. Cooperates with IL1RAP isoform 3 to mediate IL1B-induced neuronal activity including IL1B-potentiated NMDA-induced calcium influx mediated by Akt kinase activation. http://togogenome.org/gene/10090:Slc25a15 ^@ http://purl.uniprot.org/uniprot/Q543E2|||http://purl.uniprot.org/uniprot/Q9WVD5 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Inhibited by pyridoxal 5'-phosphate as well as by mercurials (mersalyl, p-chloromercuribenzene sulfonate, and mercuric chloride), N-ethylmaleimide and spermine.|||Membrane|||Mitochondrial ornithine-citrulline antiporter. Catalyzes the exchange between cytosolic ornithine and mitochondrial citrulline plus an H(+), the proton compensates the positive charge of ornithine thus leading to an electroneutral transport. Plays a crucial role in the urea cycle, by connecting the cytosolic and the intramitochondrial reactions of the urea cycle. Lysine and arginine are also transported by the antiport mechanism (By similarity). In addition, catalyzes an electroneutral exchange of ornithine or lysine for H(+), a reaction driven by the pH gradient across the inner membrane (By similarity).|||Mitochondrion inner membrane|||Mitochondrion membrane|||Widely expressed, with highest levels in the liver, testis and kidney. In the brain, expressed at high levels in the hypothalamus. http://togogenome.org/gene/10090:Dock8 ^@ http://purl.uniprot.org/uniprot/Q8C147 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DOCK family.|||Cell membrane|||Cytoplasm|||Expressed in T cells (PubMed:28028151). Expressed in bone marrow-derived dendritic cells (PubMed:25713392).|||Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:28028151, PubMed:22461490). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (PubMed:22461490, PubMed:25713392). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing (By similarity).|||In response to chemokine CXCL12/SDF-1-alpha stimulation, phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation from LRCH1.|||Interacts (via DOCKER domain) with GTPase CDC42; the interaction activates CDC42 by exchanging GDP for GTP (PubMed:22461490). The unphosphorylated form interacts (via DOCKER domain) with LRCH1 (via LRR repeats); the interaction prevents the association between DOCK8 and CDC42 (PubMed:28028151). Interacts with CCDC88B (By similarity).|||Mice are viable and fertile (PubMed:22461490). The number of CD4(+) and CD8(+) T-cells are reduced by 50 percent in the spleen and peripheral lymph nodes (PubMed:22461490). The number of marginal zone B cells in the spleen are also reduced (PubMed:22461490). In response to an immune challenge, impaired migration of epidermal dendritic cells to the draining lymph nodes resulting in a failure to prime CD4(+) T-cells characterized by a lack of CD4(+) T-cell proliferation in lymph nodes and a lack of antigen-specific IgG antibody production (PubMed:25713392, PubMed:22461490).|||Strain C3H/HeJ mice harbor a point mutation in Dock8 which results in impaired dendritic cell migration. The mutation is not observed in strains CBA/J, C3H/HeOuJ or C3HeB/FeJ.|||The DOCKER domain is necessary and sufficient for the GEF activity.|||lamellipodium membrane http://togogenome.org/gene/10090:Rnase1 ^@ http://purl.uniprot.org/uniprot/Q8C6G3 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Camk2b ^@ http://purl.uniprot.org/uniprot/P28652|||http://purl.uniprot.org/uniprot/Q5SVI2|||http://purl.uniprot.org/uniprot/Q5SVJ0|||http://purl.uniprot.org/uniprot/Q68EG2|||http://purl.uniprot.org/uniprot/Q8BL41 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.|||Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with SYNGAP1, CAMK2N2 and MPDZ (By similarity). Interacts with FOXO3 (PubMed:23805378). Interacts (when in a kinase inactive state not associated with calmodulin) with ARC; leading to target ARC to inactive synapses (By similarity). Interacts with CAMK2N1; this interaction requires CAMK2B activation by Ca(2+) (By similarity).|||Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle. In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2 (PubMed:21752990). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Thr-134' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (By similarity).|||Impaired long-term potentiation (LTP) and hippocampus-dependent learning.|||Sarcoplasmic reticulum membrane|||Synapse|||The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Ssty2 ^@ http://purl.uniprot.org/uniprot/Q149W4 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Hmgcs1 ^@ http://purl.uniprot.org/uniprot/Q8JZK9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thiolase-like superfamily. HMG-CoA synthase family.|||Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate, a precursor for cholesterol synthesis.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Plau ^@ http://purl.uniprot.org/uniprot/P06869|||http://purl.uniprot.org/uniprot/Q0VBA8 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S1 family.|||Found in high and low molecular mass forms. Each consists of two chains, A and B. The high molecular mass form contains a long chain A which is cleaved to yield a short chain A. Forms heterodimer with SERPINA5. Binds LRP1B; binding is followed by internalization and degradation. Interacts with MRC2. Interacts with PLAUR. In complex with SERPINE1, interacts with PLAUR/uPAR. Interacts with SORL1 and LRP1, either alone or in complex with SERPINE1; these interactions are abolished in the presence of LRPAP1/RAP. The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORLA.|||Inhibited by SERPINA5.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Produced as an inactive single-chain protein (pro-uPA or sc-uPA), is processed into the active disulfide-linked two-chain form of PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4.|||Secreted|||Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. http://togogenome.org/gene/10090:H1f9 ^@ http://purl.uniprot.org/uniprot/Q9QYL0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the histone H1/H5 family.|||Chromosome|||DNA-binding protein that may be implicated in chromatin remodeling and/or transcriptional regulation during spermiogenesis, the process of spermatid maturation into spermatozoa.|||Expressed exclusively in the testis by haploid germ cells (at protein level).|||Expression initiated at step 9 of spermatid development and peaked between steps 10-13. Expression decreased abruptly at step 14 and was undetectable after step 15.|||Nucleus http://togogenome.org/gene/10090:Pex26 ^@ http://purl.uniprot.org/uniprot/Q8BGI5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxin-26 family.|||Interacts (via its cytoplasmic domain) with PEX6; interaction is direct and is ATP-dependent. Interacts with PEX1; interaction is indirect and is mediated via interaction with PEX6.|||Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes. PEX26 is therefore required for the formation of the PEX1-PEX6 AAA ATPase complex, a complex that mediates the extraction of the PEX5 receptor from peroxisomal membrane.|||Peroxisome membrane http://togogenome.org/gene/10090:Armc5 ^@ http://purl.uniprot.org/uniprot/Q5EBP3 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Embryonic lethality, with its severity depending on genetic background of the mice: embryonic lethality becomes more severe with higher degrees of genetic background purity (PubMed:28169274). Knockout mice are small in body size. They have compromised T-cell proliferation and differentiation into Th1 and Th17 cells, increased T-cell apoptosis, reduced severity of experimental autoimmune encephalitis, and defective immune responses to lymphocytic choriomeningitis virus infection. They develop adrenal gland hyperplasia in old age (PubMed:28169274).|||Expression is high in the thymus, stomach, bone marrow and lymphatic tissues (including lymph nodes and intestinal wall). Also expressed in the adrenal gland, skin and in brain structures, with noticeable levels found in the cerebellum.|||In CD4(+) T-cells, mRNA expression is induced 2h after CD3E plus CD28 stimulation, then subsides and remains low between 24 and 72h post-activation.|||Involved in fetal development, T-cell function and adrenal gland growth homeostasis (PubMed:28169274). Negatively regulates adrenal cells survival. Plays a role in steroidogenesis, modulates steroidogenic enzymes expression and cortisol production (By similarity). http://togogenome.org/gene/10090:Or10d5j ^@ http://purl.uniprot.org/uniprot/Q8VF15 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Syt8 ^@ http://purl.uniprot.org/uniprot/Q9R0N6 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Cell membrane|||Cytoplasm|||Homodimer or homooligomer. Homodimerization and homooligomerization do not depend on Ca(2+). Interacts with SYNCRIP isoform 2 C-terminus. Binds inositol 1,3,4,5-tetrakisphosphate (IP4). Binds to AP2 in a Ca(2+)-independent manner. Interacts with STX1A, STX1B and STX2; the interaction is Ca(2+)-dependent.|||Involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Mediates Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. May mediate Ca(2+)-regulation of exocytosis in insulin secreted cells.|||May be due to competing donor and acceptor splice sites.|||The first C2 domain/C2A does not mediate Ca(2+)-dependent phospholipid binding.|||The second C2 domain/C2B is responsible for SYNCRIP and inositol 1,3,4,5-tetrakisphosphate (IP4)-binding.|||Ubiquitous. Detected in testis and brain. Expressed in primary neurons, neuroendocrine and endocrine cells.|||acrosome http://togogenome.org/gene/10090:Chka ^@ http://purl.uniprot.org/uniprot/O54804 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by KAT5 at Lys-243 following phosphorylation by AMPK, leading to monomerization and conversion into a tyrosine-protein kinase.|||Belongs to the choline/ethanolamine kinase family.|||Death at an early embryonic stage. Embryos die after 3 to 5 days of development.|||Expressed ubiquitously with the highest level in testis.|||Homodimer (PubMed:16490392). Heterodimer with CHKB (PubMed:16490392).|||Intron retention.|||Lipid droplet|||Monomer; acetylation by KAT5 promotes dissociation of the homodimer and monomerization.|||Phosphorylated at Ser-275 by AMPK in response to glucose deprivation, leading to localization to lipid droplets.|||Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis. Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis. Has higher activity with choline. May contribute to tumor cell growth.|||This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation (By similarity). In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets (By similarity). Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer (By similarity). Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets (By similarity).|||cytosol http://togogenome.org/gene/10090:Ash1l ^@ http://purl.uniprot.org/uniprot/Q99MY8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.|||Chromosome|||Histone methyltransferase specifically trimethylating 'Lys-36' of histone H3 forming H3K36me3 (By similarity). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (PubMed:22939622). The physiological significance of the H3K9me1 activity is unclear (Probable) (PubMed:22939622).|||Methylated at Gln-1218 by N6AMT1.|||Nucleus|||tight junction http://togogenome.org/gene/10090:Pwwp4b ^@ http://purl.uniprot.org/uniprot/Q52KH6 ^@ Similarity ^@ Belongs to the PWWP3A family. http://togogenome.org/gene/10090:Or10d4 ^@ http://purl.uniprot.org/uniprot/Q7TRA9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Plb1 ^@ http://purl.uniprot.org/uniprot/Q3TTY0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Belongs to the 'GDSL' lipolytic enzyme family. Phospholipase B1 subfamily.|||Calcium-independent membrane-associated phospholipase that catalyzes complete diacylation of phospholipids by hydrolyzing both sn-1 and sn-2 fatty acyl chains attached to the glycerol backbone (phospholipase B activity) (By similarity). Has dual phospholipase and lysophospholipase activities toward diacylphospholipids. Preferentially cleaves sn-2 ester bonds over sn-1 bonds. Acts as a lipase toward glycerolipid substrates (By similarity). Hydrolyzes fatty acyl chains of diacylglycerols with preference for the sn-2 position and of triacylglycerols with not positional selectivity (By similarity). May also hydrolyze long chain retinyl esters such as retinyl palmitate (By similarity). May contribute to digestion of dietary phospholipids, glycerolipids and retinoids, facilitating lipid absorption at the brush border (By similarity).|||Repeat 2 contains the catalytic domain.|||Undergoes proteolytic cleavage in the ileum. http://togogenome.org/gene/10090:Ankrd1 ^@ http://purl.uniprot.org/uniprot/Q9CR42 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in heart, cardiac muscle.|||Expression was first clearly detected as early as 8.5 dpc specifically in heart and is regulated temporally and spatially in the myocardium. Transcripts are present in uniformly high levels in the myocardium. Throughout cardiac development, expression is specific for the myocardium; endocardial cushions and valves exhibit only background levels of signal. Transcript levels persist but gradually decrease in neonatal, 2-week-old, and adult hearts.|||Interacts with TTN/titin and YBX1.|||May play an important role in endothelial cell activation. May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes.|||Nucleus http://togogenome.org/gene/10090:Ptcd3 ^@ http://purl.uniprot.org/uniprot/Q14C51 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS39 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins. Associated with the 12S mitochondrial rRNA (12S mt-rRNA) (By similarity).|||Mitochondrial RNA-binding protein that has a role in mitochondrial translation.|||Mitochondrion http://togogenome.org/gene/10090:Ifitm10 ^@ http://purl.uniprot.org/uniprot/Q8BR26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CD225/Dispanin family.|||Cell membrane http://togogenome.org/gene/10090:A4galt ^@ http://purl.uniprot.org/uniprot/Q0R0H6|||http://purl.uniprot.org/uniprot/Q3TRS1|||http://purl.uniprot.org/uniprot/Q3UF00|||http://purl.uniprot.org/uniprot/Q67BJ4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 32 family.|||Catalyzes the transfer of galactose from UDP-alpha-D-galactose to lactosylceramide/beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1)-ceramide(d18:1(4E)) to produce globotriaosylceramide/globoside Gb3Cer (d18:1(4E)). Also able to transfer galactose to galactosylceramide/beta-D-Gal-(1<->1')-Cer. Globoside Gb3Cer is a glycosphingolipid of the globo serie, one of the major types of neutral root structures of glycosphingolipids, that constitute a significant portion of mammalian cell membranes.|||Golgi apparatus membrane|||The conserved DXD motif is involved in enzyme activity. http://togogenome.org/gene/10090:Gemin2 ^@ http://purl.uniprot.org/uniprot/Q9CQQ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gemin-2 family.|||Cytoplasm|||Monomer (By similarity). Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (By similarity). Interacts with GEMIN5; the interaction is direct (By similarity). Interacts (via C-terminus) with SMN1; the interaction is direct (By similarity). Interacts with GEMIN5; the interaction is direct (By similarity). Interacts with SNRPD1; the interaction is direct (By similarity). Interacts with SNRPD2; the interaction is direct (By similarity). Interacts (via N-terminus) with SNRPF; the interaction is direct (By similarity). Interacts (via N-terminus) with SNRPE; the interaction is direct (By similarity). Interacts (via N-terminus) with SNRPG; the interaction is direct (By similarity).|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs (By similarity). Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core) (By similarity). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG (5Sm) are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP (By similarity). To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A (By similarity). Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP (By similarity). Within the SMN complex, GEMIN2 constrains the conformation of 5Sm, thereby promoting 5Sm binding to snRNA containing the snRNP code (a nonameric Sm site and a 3'-adjacent stem-loop), thus preventing progression of assembly until a cognate substrate is bound (By similarity).|||gem http://togogenome.org/gene/10090:Tmem19 ^@ http://purl.uniprot.org/uniprot/A0A1W2P7R5|||http://purl.uniprot.org/uniprot/Q91W52 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM19 family.|||Membrane http://togogenome.org/gene/10090:Il2 ^@ http://purl.uniprot.org/uniprot/P04351 ^@ Disruption Phenotype|||Function|||Induction|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the IL-2 family.|||By bacterial infection.|||Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance (PubMed:9814585, PubMed:14614860). Binds to a receptor complex composed of either the high-affinity trimeric IL-2R (IL2RA/CD25, IL2RB/CD122 and IL2RG/CD132) or the low-affinity dimeric IL-2R (IL2RB and IL2RG). Interaction with the receptor leads to oligomerization and conformation changes in the IL-2R subunits resulting in downstream signaling starting with phosphorylation of JAK1 and JAK3. In turn, JAK1 and JAK3 phosphorylate the receptor to form a docking site leading to the phosphorylation of several substrates including STAT5 (PubMed:14614860, PubMed:27018889). This process leads to activation of several pathways including STAT, phosphoinositide-3-kinase/PI3K and mitogen-activated protein kinase/MAPK pathways. Functions as a T-cell growth factor and can increase NK-cell cytolytic activity as well. Promotes strong proliferation of activated B-cells and subsequently immunoglobulin production. Plays a pivotal role in regulating the adaptive immune system by controlling the survival and proliferation of regulatory T-cells, which are required for the maintenance of immune tolerance (PubMed:14614860). Moreover, participates in the differentiation and homeostasis of effector T-cell subsets, including Th1, Th2, Th17 as well as memory CD8-positive T-cells (PubMed:9814585).|||Mutant mice exhibit lethal autoimmunity and are impaired in regulatory T-cell production. After 4 to 5 weeks of birth, they develop a thymic disorder resulting in the disruption of thymocyte maturation.|||Produced by immune cells including dendritic cells. In contrast, macrophages do not produce IL2 upon bacterial stimulation.|||Secreted|||The poly-Gln region is highly polymorphic. http://togogenome.org/gene/10090:Manf ^@ http://purl.uniprot.org/uniprot/Q9CXI5 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ARMET family.|||By endoplasmic reticulum (ER) stress.|||Endoplasmic reticulum lumen|||Expressed from birth.|||Interacts with HSPA5; the interaction is direct (By similarity). Component of a complex containing at least CRELD2, MANF, MATN3 and PDIA4 (PubMed:23956175).|||Sarcoplasmic reticulum lumen|||Secreted|||Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain. Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra. Enhances spontaneous, as well as evoked, GABAergic inhibitory postsynaptic currents in dopaminergic neurons. Inhibits cell proliferation and endoplasmic reticulum (ER) stress-induced cell death. Retained in the ER/sarcoplasmic reticulum (SR) through association with the endoplasmic reticulum chaperone protein HSPA5 under normal conditions. Up-regulated and secreted by the ER/SR in response to ER stress and hypoxia. Following secretion by the ER/SR, directly binds to 3-O-sulfogalactosylceramide, a lipid sulfatide in the outer cell membrane of target cells. Sulfatide binding promotes its cellular uptake by endocytosis, and is required for its role in alleviating ER stress and cell toxicity under hypoxic and ER stress conditions.|||Strongly expressed in pancreatic islets and spermatocytes (at protein level). Expressed in chondrocytes (at protein level) (PubMed:23956175).|||The N-terminal region may be responsible for neurotrophic activity while the C-terminal region may play a role in the ER stress response. http://togogenome.org/gene/10090:Icosl ^@ http://purl.uniprot.org/uniprot/Q9JHJ8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Cell membrane|||Detected early in hemopoiesis: in the yolk sac at 11.5 and 12.5 dpc and, to a lesser extent, in the liver at 14.5 dpc.|||Interacts with CTLA4 (in vitro).|||Isoform 1 highest expression in lymphoid tissues, such as spleen (mostly in the marginal zone), lymph nodes (particularly in the cortex and in both primary and secondary follicles), thymus (predominantly in the medulla) and Peyer patches (mostly in the follicles), lower levels in many non-lymphoid tissues, such as brain, heart, kidney, liver, lung, skeletal muscle and testis. Present on freshly isolated splenic B-cells, T-cells, dendritic cells and macrophages. The expression of isoform 2 is restricted to heart, spleen and kidney.|||Ligand for the T-cell-specific cell surface receptor ICOS. Acts as a costimulatory signal for T-cell proliferation and cytokine secretion; induces also B-cell proliferation and differentiation into plasma cells. Could play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function. During pregnancy, may function to skew the cytokine of maternal T-cells toward immunoprotective Th2 phenotype. http://togogenome.org/gene/10090:Cdc42ep4 ^@ http://purl.uniprot.org/uniprot/Q9JM96 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BORG/CEP family.|||Endomembrane system|||Interacts with CDC42 and RHOQ, in a GTP-dependent manner.|||Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation, when overexpressed in fibroblasts.|||Ubiquitous.|||cytoskeleton http://togogenome.org/gene/10090:Tex14 ^@ http://purl.uniprot.org/uniprot/Q7M6U3 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Cytoplasm|||Detected at low levels in developing testis at 5 and 10 days after birth. Highly expressed in testis 15 and 20 days after birth. Highly expressed in pachytene, diplotene and meiotically dividing spermatocytes and in early round spermatids.|||Detected in testis and spermatogonia. Not detectable in the other tissues tested.|||Interacts with KIF23 and RBM44. Interacts with CEP55; inhibiting interaction between CEP55 and PDCD6IP/ALIX and TSG101.|||Male mice are sterile, due to the absence of intercellular bridges. Intercellular bridges do not form during spermatogenesis, and male mice are sterile. In females, embryonic intercellular bridges are also absent, mice have fewer oocytes, but they are fertile.|||Midbody|||Phosphorylated on Thr residues by CDK1 during early phases of mitosis, promoting the interaction with PLK1 and recruitment to kinetochores. Phosphorylated on Ser-431 by PLK1 during late prometaphase promotes the rapid depletion from kinetochores and its subsequent degradation by the APC/C complex.|||Required both for the formation of intercellular bridges during meiosis and for kinetochore-microtubule attachment during mitosis. Intercellular bridges are evolutionarily conserved structures that connect differentiating germ cells and are required for spermatogenesis and male fertility. Acts by promoting the conversion of midbodies into intercellular bridges via its interaction with CEP55: interaction with CEP55 inhibits the interaction between CEP55 and PDCD6IP/ALIX and TSG101, blocking cell abscission and leading to transform midbodies into intercellular bridges. Also plays a role during mitosis: recruited to kinetochores by PLK1 during early mitosis and regulates the maturation of the outer kinetochores and microtubule attachment. Has no protein kinase activity in vitro.|||Ser-370 is present instead of the conserved Asp which is expected to be an active site residue.|||The GPPX3Y motif mediates interaction with CEP55.|||The protein kinase domain is predicted to be catalytically inactive.|||Used as a marker for intercellular bridges.|||kinetochore http://togogenome.org/gene/10090:Zfp397 ^@ http://purl.uniprot.org/uniprot/Q7TNK4 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Gabra2 ^@ http://purl.uniprot.org/uniprot/P26048|||http://purl.uniprot.org/uniprot/Q544G1 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by pentobarbital (By similarity). Inhibited by the antagonist bicuculline (By similarity).|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA2 sub-subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Glycosylated.|||Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:11528422). Interacts with UBQLN1 (PubMed:11528422). Interacts with KIF21B (By similarity). Interacts with LHFPL4 (PubMed:28978485, PubMed:11528422) (By similarity). Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (PubMed:31601770).|||Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha2/beta2/gamma2 receptor exhibits synaptogenic activity whereas the alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (PubMed:27129275).|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane|||The extracellular domain contributes to synaptic contact formation.|||dendrite http://togogenome.org/gene/10090:Irx1 ^@ http://purl.uniprot.org/uniprot/P81068 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TALE/IRO homeobox family.|||Expressed in specific and overlapping patterns with Irx1 and Irx2 in the developing and adult metanephric kidney. In the adult metanephros, renal expression is found in the loop of Henle in the S3 proximal tubule segment and in the thick ascending limb (TAL) of the distal tubule.|||First detected in the mesoderm at stage 7.5 dpc. During neurogenesis (9.5 dpc to 10.5 dpc), predominantly expressed along the anteroposterior axis of the CNS in the mesencephalon, metencephalon, rhombencephalon and spinal cord, with expression excluded from the midbrain-hindbrain junction. Beginning at 9.5 dpc, expression is found in the epithelial component of the branchial arches and foregut. At later stages, expressed in somites. At 10.5 dpc, expressed in the cephalic mesenchyme surrounding the optic vesicle. By 12.5 dpc, expression remains in the mesenchyme and also begins in the neuroretina, and at 16.5 dpc expression is exclusively located in the inner neuroblast layers of the neuroretina. Starting at the otic vesicle stage, shows regionalized expression in the developing inner ear with expression in the entire otic vesicle from 10.5 dpc onwards. Expressed in distinct patterns in the developing limb buds from 10.5 dpc onwards. Expressed in the developing heart in the ventricular septum from the onset of its formation (10.5 dpc) onward. In fetal stages, expression becomes confined to the myocardium of the atrioventricular bundle and bundle branches of the forming ventricular conduction system.|||Nucleus http://togogenome.org/gene/10090:Sh2d3c ^@ http://purl.uniprot.org/uniprot/Q9QZS8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an adapter protein that mediates cell signaling pathways involved in cellular functions such as cell adhesion and migration, tissue organization, and the regulation of the immune response (PubMed:20505138, PubMed:20881139, PubMed:20956287). Plays a role in integrin-mediated cell adhesion through BCAR1-CRK-RAPGEF1 signaling and activation of the small GTPase RAP1 (By similarity). Promotes cell migration and invasion through the extracellular matrix (PubMed:20881139). Required for marginal zone B-cell development and thymus-independent type 2 immune responses (PubMed:20505138, PubMed:20956287). Mediates migration and adhesion of B cells in the splenic marginal zone via promoting hyperphosphorylation of NEDD9/CASL (PubMed:20505138). Plays a role in CXCL13-induced chemotaxis of B-cells (PubMed:20505138, PubMed:20956287). Plays a role in the migration of olfactory sensory neurons (OSNs) into the forebrain and the innervation of the olfactory bulb by the OSN axons during development (PubMed:20881139). Required for the efficient tyrosine phosphorylation of BCAR1 in OSN axons (PubMed:20881139).|||Cell membrane|||Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK (By similarity). Within the complex, interacts with CRK and (via C-terminus) with BCAR1/CAS (via C-terminus) (PubMed:10692442, PubMed:17174122). Interacts with NEDD9/HEF1 (PubMed:20956287). Interacts with EPHB2 (PubMed:10542222).|||Cytoplasm|||Expressed in hematopoietic cells from spleen, lymph node and thymus (at protein level) (PubMed:10542222, PubMed:10692442, PubMed:12486027). Expressed weakly in the lung (at protein level) (PubMed:10692442).|||Expressed in the brain, lung, kidney, and weakly expressed in the liver and lung (at protein level).|||Expressed in the developing OSNs at dpc 13.5 and 14.5 with reduced expression at dpc 16.5.|||Expressed in the olfactory bulb and olfactory sensory neurons (at protein level) (PubMed:20881139). Expressed in B cells (at protein level) (PubMed:20505138, PubMed:20956287). Expressed in T lymphocytes (PubMed:17174122).|||Important regulator of chemokine-induced, integrin-mediated T lymphocyte adhesion and migration, acting upstream of RAP1 (PubMed:17174122). Required for tissue-specific adhesion of T lymphocytes to peripheral tissues (PubMed:17174122). Required for basal and CXCL2 stimulated serine-threonine phosphorylation of NEDD9 (PubMed:17174122). May be involved in the regulation of T-cell receptor-mediated IL2 production through the activation of the JNK pathway in T-cells (PubMed:12486027).|||In one study knockout mice are viable and born at the expected Mendelian rate (PubMed:20505138). In another study the majority of knockout mice die after birth, those that survive show severe lamination defects and loss of cellular organization in their olfactory bulb, with a reduction in gonadotropin-releasing hormone in the preoptic region of the hypothalamus (PubMed:20881139). Mice that die at birth are morphologically normal apart from a marked reduction in the size of the olfactory bulb, which exhibits abnormal cellular organization in the outer layers and a lack of innervation of OSNs (PubMed:20881139). At dpc 16.5 OSNs fail to extend into the marginal zone of the forming olfactory bulb from the basement membrane, and show a reduction in tyrosine phosphorylated BCAR1 (PubMed:20881139). Decrease in B cells in the splenic marginal zone (PubMed:20505138, PubMed:20956287).|||Interacts (via C-terminus) with BCAR1/CAS (via C-terminus) (PubMed:10692442). Interacts with IGF1 (PubMed:20881139).|||Interacts with NEDD9/HEF1 (PubMed:10692442, PubMed:17174122). Interacts with BCAR1/CAS (PubMed:10692442). Interacts with PTK2B (PubMed:12486027).|||It is unclear if the knockout of Sh2d3c causes lethality (PubMed:20505138, PubMed:20881139). One report in genetic knockout mice suggests it is viable (PubMed:20505138). Another report in the same strain but a different genetic knockout model suggests lethality (PubMed:20881139).|||May be involved in the BCAR1/CAS-mediated JNK activation pathway.|||Phosphorylated by MAPK/ERK upon T-cell receptor stimulation in T-cells.|||The C-terminal Cdc25-homology/Ras-GEF domain adopts a closed conformation rendering it incapable of carrying out canonical exchange factor function, this closed conformation is required for interaction with BCAR1.|||axon|||ruffle membrane http://togogenome.org/gene/10090:Cd8b1 ^@ http://purl.uniprot.org/uniprot/P10300|||http://purl.uniprot.org/uniprot/Q3TEK8 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Forms disulfide-linked heterodimers with CD8A at the cell surface. Interacts with CD3D; this interaction couples TCR-CD3 with CD8. Interacts with LCK.|||Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. A palmitoylation site in the cytoplasmic tail of CD8B chain contributes to partitioning of CD8 into the plasma membrane lipid rafts where signaling proteins are enriched. Once LCK recruited, it initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). Additionally, plays a critical role in thymic selection of CD8+ T-cells.|||Membrane|||Palmitoylated at the cytoplasmic tail and thereby targets the heterodimer CD8A/CD8B to lipid rafts unlike CD8A homodimers.|||The lack of Cd8b reduces but does not completely abolish thymic maturation of CD8+ T-cells. However, Cd8-depleted mice mount normal primary cytotoxic CD8 responses upon acute viral infections. http://togogenome.org/gene/10090:Ado ^@ http://purl.uniprot.org/uniprot/Q6PDY2 ^@ Function|||Subunit|||Tissue Specificity ^@ Monomer.|||Plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate (PubMed:17581819, PubMed:32601061). Catalyzes the oxidation of cysteamine (2-aminoethanethiol) to hypotaurine (PubMed:17581819, PubMed:32601061). Catalyzes the oxidation of the regulator of G-protein signaling 5 (RGS5) (PubMed:32601061). Also oxidizes proteins RGS4 and interleukin-32 (IL32) (By similarity).|||Ubiquitous, with highest expression in brain, heart and skeletal muscle (at protein level). http://togogenome.org/gene/10090:Cd247 ^@ http://purl.uniprot.org/uniprot/A2MZG6|||http://purl.uniprot.org/uniprot/P24161|||http://purl.uniprot.org/uniprot/Q3UU54 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD3Z/FCER1G family.|||CD3Z deletion causes severely defective thymocyte differentiation (PubMed:8223495). Absence of CD3Z also leads to altered dendritic structure and motility in developing retina (PubMed:20188655).|||CD3Z is expressed in normal lymphoid tissue and in peripheral blood mononuclear cells (PBMCs). Expressed also in retinal ganglion cells (PubMed:20188655).|||Cell membrane|||Membrane|||Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme. Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN).|||Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.|||The ITAM domains mediate interaction with SHB.|||The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with SLA (PubMed:10662792). Interacts with SLA2 (PubMed:11891219). Interacts with TRAT1. Interacts with DOCK2. Interacts with SHB. Interacts with ZAP70. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain). Interacts with PTPRC (By similarity). Interacts with CRK; this interaction regulates CD3Z phosphorylation (By similarity). Interacts (on T cell side) with CD81, ICAM1 and CD9 at immunological synapses between antigen-presenting cells and T cells. Interacts with CD160. Interacts with LY6E. Interacts with LY6E (By similarity). The signaling subunit of immunoglobulin gamma (IgG) Fc receptor complex. As a homodimer or a heterodimer with FCER1G, associates with the ligand binding subunit FCGR3A (via transmembrane domain); this interaction is a prerequisite for Fc receptor complex expression on the cell surface. http://togogenome.org/gene/10090:Ndufaf7 ^@ http://purl.uniprot.org/uniprot/Q9CWG8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Arginine methyltransferase involved in the assembly or stability of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Acts by mediating symmetric dimethylation of 'Arg-118' of NDUFS2 after it assembles into the complex I, stabilizing the early intermediate complex.|||Belongs to the NDUFAF7 family.|||Embryonic lethality.|||Interacts with NDUFS2.|||Mitochondrion http://togogenome.org/gene/10090:Rimoc1 ^@ http://purl.uniprot.org/uniprot/Q8BR90 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RIMOC1 family.|||Interacts with the MON1A-CCZ1B complex. Interacts with GDP-bound RAB7A and promotes its interaction with the MON1A-CCZ1B complex.|||Plays an important role in the removal of damaged mitochondria via mitophagy by controlling the stability and localization of RAB7A (By similarity). Required for the recruitment of RAB7A and ATG9A vesicles to damaged mitochondria and promotes the stability of RAB7A by inhibiting its proteasomal degradation during mitophagy (By similarity).|||cytosol http://togogenome.org/gene/10090:Urb1 ^@ http://purl.uniprot.org/uniprot/Q571H0 ^@ Subcellular Location Annotation ^@ nucleolus http://togogenome.org/gene/10090:Rraga ^@ http://purl.uniprot.org/uniprot/Q80X95 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTR/RAG GTP-binding protein family.|||Can occur as a homodimer or as a heterodimer with RRAGC or RRAGD in a sequence-independent manner; heterodimerization stabilizes proteins of the heterodimer (By similarity). The GTP-bound form of RRAGA (in complex with the GDP-bound form of RRAGC or RRAGD) interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (By similarity). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (By similarity). The Rag heterodimer interacts with the Ragulator complex (By similarity). The GTP-bound form of RRAGA interacts with NOL8 (By similarity). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGA and is negatively regulated by amino acids (By similarity). Interacts (polyubiquitinated) with TSC2 (By similarity). Interacts with SESN1, SESN2 and SESN3 (By similarity). Interacts with PIP4P1 (PubMed:29644770). Interacts with GPR137B (By similarity).|||Cytoplasm|||Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:23263183). Forms heterodimeric Rag complexes with RagC/RRAGC or RagD/RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form: RagA/RRAGA is in its active form when GTP-bound RagA/RRAGA forms a complex with GDP-bound RagC/RRAGC (or RagD/RRAGD) and in an inactive form when GDP-bound RagA/RRAGA heterodimerizes with GTP-bound RagC/RRAGC (or RagD/RRAGD) (PubMed:23263183). In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:23263183). Involved in the RCC1/Ran-GTPase pathway (By similarity). May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death (By similarity).|||Lysosome membrane|||Nucleus|||Polybiquitinated via 'Lys-63'-linked polyubiquitination by RNF152 in response to amino acid starvation: polyubiquitination of the GDP-bound inactive form by RNF152 promotes RRAGA inactivation and interaction with the GATOR1 complex. This does not affect RRAGA degradation.|||The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (By similarity). The Ragulator complex functions as a GEF and promotes the active GTP-bound form (By similarity). The GATOR1 complex functions as a GAP and stimulates RRAGA GTPase activity to turn it into its inactive GDP-bound form, preventing mTORC1 recruitment and activation (By similarity). http://togogenome.org/gene/10090:Pnma2 ^@ http://purl.uniprot.org/uniprot/Q8BHK0 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PNMA family.|||Expressed in the cerebrum, cerebellum and testis.|||nucleolus http://togogenome.org/gene/10090:Usp7 ^@ http://purl.uniprot.org/uniprot/E9PXY8|||http://purl.uniprot.org/uniprot/F8VPX1|||http://purl.uniprot.org/uniprot/Q6A4J8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Chromosome|||Cytoplasm|||Expressed in embryo at 3.5 and from 7.5 to 10.5 dpc (at protein level).|||Hydrolase that deubiquitinates target proteins such as FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:21268065, PubMed:14719112, PubMed:19946331). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Deubiquitinates KMT2E preventing KMT2E proteasomal-mediated degradation (By similarity). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (By similarity). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (By similarity). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (By similarity). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:27863226). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins (PubMed:27123980). Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells (By similarity). Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis (By similarity). Involved in the regulation of WASH-dependent actin polymerization at the surface of endosomes and the regulation of endosomal protein recycling (By similarity). It maintains optimal WASH complex activity and precise F-actin levels via deubiquitination of TRIM27 and WASHC1 (By similarity). Mediates the deubiquitination of phosphorylated DEPTOR, promoting its stability and leading to decreased mTORC1 signaling (By similarity).|||Led to early embryonic lethality. Show disorganized germinal layers without the formation of a proamniotic cavity. Many of the surviving cells were trophoblastic giant cells with large nuclei.|||Monomer. Homodimer. Part of a complex with DAXX, MDM2, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts with MDM2; the interaction is independent of p53/TP53. Interacts with DAXX; the interaction is direct and independent of MDM2 and p53/TP53. Component of a complex composed of KMT2E, OGT and USP7; the complex stabilizes KMT2E, preventing KMT2E ubiquitination and proteasomal-mediated degradation (By similarity). Interacts (via MATH domain) with KMT2E (By similarity). Interacts with OGT (By similarity). Interacts with FOXO4; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of p53/TP53. Interacts with p53/TP53; the interaction is enhanced in response to DNA damage; the interaction is impaired by TSPYL5. Interacts with PTEN; the interaction is direct. Interacts with ATXN1 and the strength of interaction is influenced by the length of the poly-Gln region in ATXN1. A weaker interaction seen with mutants having longer poly-Gln regions. Interacts with KIAA1530/UVSSA. Interacts with MEX3C and antagonizes its ability to degrade mRNA (By similarity). Interacts with DNMT1 and UHRF1 (PubMed:21268065). Interacts with FOXP3 (By similarity). Interacts (via MATH domain) with RNF220 (By similarity). Associated component of the Polycomb group (PcG) multiprotein PRC1-like complex (By similarity). Interacts with EPOP (PubMed:27863226). Interacts with OTUD4 and USP9X; the interaction is direct (By similarity). Interacts with CRY2 (By similarity). Interacts with REST (By similarity). Interacts with ERCC6 (By similarity). Part of a complex consisting of USP7, MAGEL2 and TRIM27; directly interacts with MAGEL2; directly interacts with TRIM27 (By similarity).|||Not sumoylated.|||Nucleus|||PML body|||Polyneddylated.|||Polyubiquitinated. Ubiquitinated at Lys-870 (By similarity).|||The C-terminus plays a role in its oligomerization.|||Widely expressed. High expression is detected in brain, bone marrow, thymus and testis. http://togogenome.org/gene/10090:Chrnb3 ^@ http://purl.uniprot.org/uniprot/Q3UZS0|||http://purl.uniprot.org/uniprot/Q8BMN3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-3/CHRNB3 sub-subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Neuronal AChR seems to be composed of two different types of subunits: alpha and beta.|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Nsrp1 ^@ http://purl.uniprot.org/uniprot/Q5NCR9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NSRP1 family.|||Interacts (via C-terminus) with SRSF1. Interacts (via C-terminus) with SRSF2 (By similarity).|||Mice show early embryonic lethality shortly after implantation.|||Nucleus|||Nucleus speckle|||RNA-binding protein that mediates pre-mRNA alternative splicing regulation. http://togogenome.org/gene/10090:Or5d18 ^@ http://purl.uniprot.org/uniprot/Q920P2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tspyl1 ^@ http://purl.uniprot.org/uniprot/O88852 ^@ Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the nucleosome assembly protein (NAP) family.|||Detected in embryo at 10.5 dpc.|||Highly expressed in testis, ovary, liver, spleen, brain, kidney, prostate, lung, and heart. Low expression in liver.|||Ubiquitinated by the CRL2(APPBP2) complex, which recognizes the Arg-Xaa-Xaa-Gly sequence at the C-terminus, leading to its degradation.|||nucleolus http://togogenome.org/gene/10090:Erlec1 ^@ http://purl.uniprot.org/uniprot/Q8VEH8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum lumen|||May form a complex with OS9, HSPA5, SYVN1, and SEL1L with which it interacts directly. Interacts (via PRKCSH 2 domain) with KREMEN2 (when glycosylated). Interacts with HSPA5 (By similarity).|||N-glycosylated.|||Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins (By similarity). http://togogenome.org/gene/10090:Prss45 ^@ http://purl.uniprot.org/uniprot/Q8K4I7 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||In contrast to other members of the family, lacks the conserved Ser at position 243 which is replaced by a Pro residue, suggesting it is inactive.|||Secreted http://togogenome.org/gene/10090:Pinlyp ^@ http://purl.uniprot.org/uniprot/B2RSX2|||http://purl.uniprot.org/uniprot/Q9CQD7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CNF-like-inhibitor family.|||Secreted http://togogenome.org/gene/10090:Ttpa ^@ http://purl.uniprot.org/uniprot/Q8BWP5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds (+)-alpha-tocopherol, enhances its transfer between separate membranes, and stimulates its release from liver cells. Binds both phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate; the resulting conformation change is important for the release of the bound alpha-tocopherol.|||Cytoplasm|||Monomer and homotetramer. Phosphatidylinositol 4,5-bisphosphate binding induces the formation of homotetramers. Phosphatidylinositol 3,4-bisphosphate is less efficient in inducing tetramerization. http://togogenome.org/gene/10090:Stab2 ^@ http://purl.uniprot.org/uniprot/E5RKF9|||http://purl.uniprot.org/uniprot/Q8R4U0 ^@ Caution|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expressed in endothelial sinuses of liver, lymph nodes, bone marrow, spleen and in specialised structures of eye, heart, brain and kidney. Expression is detected in corneal and lens epithelium, in mesenchymal cells of the heart valves, in the ependymal cells lining the ventricles in the brain, and in the prismatic epithelial cells covering the renal papillae.|||Glycosylated.|||Interacts with heparin, alpha-M/beta-2 integrin (ITGAM and ITGB2), and thymosin beta 4 (TMSB4X) (By similarity). Interacts with GULP1. Associates with clathrin and adapter protein AP-2; in liver sinusoidal endothelial cells (LSECs).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Phosphatidylserine receptor that enhances the engulfment of apoptotic cells. Hyaluronan receptor that binds to and mediates endocytosis of hyaluronic acid (HA). Acts also, in different species, as a primary systemic scavenger receptor for heparin (Hep), chondroitin sulfate (CS), dermatan sulfate (DS), nonglycosaminoglycan (GAG), acetylated low-density lipoprotein (AcLDL), pro-collagen propeptides and advanced glycation end products (AGE). May serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan. Counter receptor which plays an important role in lymphocyte recruitment in the hepatic vasculature. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. The proteolytically processed short form also functions as an endocytosis receptor for heparin internalization as well as HA and CS.|||Proteolytically processed to yield a smaller protein.|||Recognizes phosphatidyl serine via its epidermal growth factor-like domains. http://togogenome.org/gene/10090:Gpx3 ^@ http://purl.uniprot.org/uniprot/P46412 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutathione peroxidase family.|||Homotetramer.|||Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione.|||Secreted|||Secreted in plasma. http://togogenome.org/gene/10090:Xab2 ^@ http://purl.uniprot.org/uniprot/Q9DCD2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with RNA polymerase II, the TCR-specific proteins CKN1/CSA and ERCC6/CSB, and XPA. Identified in the spliceosome C complex. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex. The IB complex does not contain PRPF19.|||Belongs to the crooked-neck family.|||Complete embryonic lethality before 13.5 dpc. Already at 3.5 dpc, the number of homozygous mutant embryos is lower than expected.|||Involved in pre-mRNA splicing as component of the spliceosome. Involved in transcription-coupled repair (TCR), transcription and pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Or7a40 ^@ http://purl.uniprot.org/uniprot/A2RSZ3|||http://purl.uniprot.org/uniprot/Q9JHB2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Kif21a ^@ http://purl.uniprot.org/uniprot/F8WGN6|||http://purl.uniprot.org/uniprot/Q3TQJ5|||http://purl.uniprot.org/uniprot/Q3UHE7|||http://purl.uniprot.org/uniprot/Q3V416|||http://purl.uniprot.org/uniprot/Q9QXL2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Interacts (via residues 1148-1169) with KANK1 (via ankyrin repeats 1-5) and KANK2 (via ankyrin repeats 1-5).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Microtubule-binding motor protein probably involved in neuronal axonal transport. In vitro, has a plus-end directed motor activity.|||Widely expressed, with highest expression in brain.|||axon|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Sav1 ^@ http://purl.uniprot.org/uniprot/Q8VEB2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expression was detected in 7 dpc embryos. Expression levels decreased at day 11 and remained low at days 15 and 17.|||Homodimer. Stabilized through interaction with STK3/MST2 or STK4/MST1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of STK3/MST2. Interacts with WTIP and AJUBA.|||Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age. Embryos display unchecked proliferation and defects in terminal differentiation of epithelial cells.|||Nucleus|||Phosphorylated by STK3/MST2 and STK4/MST1. Phosphorylation is not required for SAV1 stability and may increase the number of protein binding sites on the scaffold molecule (By similarity).|||Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (By similarity).|||Ubiquitously expressed in adult tissues with the highest level found in testis. http://togogenome.org/gene/10090:Tmem266 ^@ http://purl.uniprot.org/uniprot/Q8BZB3 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Homodimer; disulfide-linked.|||In brain, present in the granule layer of the cerebellar cortex (PubMed:25165868). Localizes on the post-synaptic side of glutamatergic mossy fibers and granule cells in the cerebellum (at protein level) (PubMed:25165868).|||Perikaryon|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Transplantation of the transmembrane segment S4 into HVCN1, generates a functional voltage-activated proton channel.|||Voltage-sensor protein present on the post-synaptic side of glutamatergic mossy fibers and granule cells in the cerebellum. Despite the presence of a voltage-sensor segment, does not form a functional ion channel and its precise role remains unclear. Undergoes both rapid and slow structural rearrangements in response to changes in voltage. Contains a zinc-binding site that can regulate the slow conformational transition.|||dendrite http://togogenome.org/gene/10090:Pramel51 ^@ http://purl.uniprot.org/uniprot/L7N1Y3 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Prim1 ^@ http://purl.uniprot.org/uniprot/P20664|||http://purl.uniprot.org/uniprot/Q5FW94 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the eukaryotic-type primase small subunit family.|||Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:8253737, PubMed:8026492). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:8253737). Can add both ribo- and deoxynucleotides during elongation of the primers (PubMed:8253737). Synthesizes 9-mer RNA primers (also known as the 'unit length' RNA primers) (By similarity). Incorporates only ribonucleotides in the presence of ribo- and deoxy-nucleotide triphosphates (rNTPs, dNTPs). Requires template thymine or cytidine to start the RNA primer synthesis, with an adenine or guanine at its 5'-end (By similarity). Binds single stranded DNA (PubMed:8253737).|||Heterodimer of a catalytic subunit PRIM1 and a regulatory subunit PRIM2, also known as the DNA primase complex (PubMed:8253737, PubMed:8026492). Interacts with PRIM2/p58 (via C-terminus) (By similarity). Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:8253737). Within the complex, POLA1 directly interacts with PRIM2 (PubMed:8253737).|||The bound zinc ion is not a cofactor. It is bound to a zinc knuckle motif that may be involved in sequence recognition and the binding of ssDNA (By similarity).|||The catalytic domain (residues 1-190 and 303-408) adopts a typical 'prim' fold structure formed by two three strand beta-sheets that line the inside of the lower and upper parts, each surrounded by alpha-helices on the outside. It comprises a highly conserved catalytic triad, a structural zinc-binding motif and the nucleotide-binding motifs. The Asp-109, Asp-111 and Asp-305 catalytic triad binds two Mn2+ or Mg2+ ions which activate for nucleophilic attack the 3'-hydroxyl of the growing RNA primer or of the first NTP bound at the initiation site. The nucleotide-binding motifs coordinate the phosphates, the ribose and the base of a NTP molecule. The interaction between O2' of the initiating NTP and Asp-305 stabilizes the ribose during the di-nucleotide synthesis. It is proposed that the first nucleotide binds to the elongation site, followed by binding to the initiation site of a second NTP, which will become the 5'-terminal nucleotide of the primer.|||The presence of the regulatory subunit PRIM2/p58 accelerates the kinetics of initiation and primer extension. http://togogenome.org/gene/10090:Mettl21c ^@ http://purl.uniprot.org/uniprot/Q8BLU2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METTL21 family.|||Interacts with members of the heat shock protein 70 families; these proteins may possibly be methylation substrates for the enzyme.|||Nucleus|||Protein-lysine methyltransferase. http://togogenome.org/gene/10090:Pus1 ^@ http://purl.uniprot.org/uniprot/H7BX59|||http://purl.uniprot.org/uniprot/Q9WU56 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tRNA pseudouridine synthase TruA family.|||Cytoplasm|||Does not form pseudouridine when expressed in vitro.|||Impaired muscle morphology and physiology leading to impaired exercise capacity (PubMed:27197761). Mice were born at the expected Mendelian frequency (PubMed:27197761). At 14 weeks, mice display reduced exercise capacity, probably caused by alterations in muscle metabolism related to mitochondrial content and oxidative capacity (PubMed:27197761). Cells show reduced pseudouridylation of cytoplasmic and mitochondrial tRNAs (PubMed:27197761).|||Mitochondrion|||Monomer (By similarity). Forms a complex with RARG and the SRA1 RNA in the nucleus (PubMed:15327771).|||Nucleus|||Pseudouridylate synthase that catalyzes pseudouridylation of tRNAs and mRNAs (PubMed:10094309, PubMed:15327771, PubMed:27197761). Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA (PubMed:10094309). Also catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of mRNAs with the consensus sequence 5'-UGUAG-3' (By similarity). Acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions (By similarity). Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3'-end processing (By similarity). Involved in regulation of nuclear receptor activity through pseudouridylation of SRA1 mRNA (PubMed:15327771). http://togogenome.org/gene/10090:Spata2l ^@ http://purl.uniprot.org/uniprot/Q8BNN1 ^@ Similarity ^@ Belongs to the SPATA2 family. http://togogenome.org/gene/10090:Gabbr1 ^@ http://purl.uniprot.org/uniprot/Q9WV18 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling.|||Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.|||Cell membrane|||Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:10773016, PubMed:10075644). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10773016, PubMed:10075644). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (By similarity). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:10075644). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (By similarity).|||Expressed in neuronal tissue including cortex, cerebellum and spinal cord. Not detected in non-neuronal tissues including heart, liver, spleen and kidney.|||Heterodimer of GABBR1 and GABBR2 (PubMed:10773016, PubMed:10075644, PubMed:9872744). Homodimers may form, but are inactive (By similarity). Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity). Interacts with JAKMIP1 (PubMed:14718537).|||Postsynaptic cell membrane|||dendrite http://togogenome.org/gene/10090:Or13p5 ^@ http://purl.uniprot.org/uniprot/Q8VGB1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Vps26b ^@ http://purl.uniprot.org/uniprot/Q8C0E2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as component of the retromer cargo-selective complex (CSC) (PubMed:21040701, PubMed:21920005). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (By similarity). May be involved in retrograde transport of SORT1 but not of IGF2R (PubMed:21040701). Acts redundantly with VSP26A in SNX-27 mediated endocytic recycling of SLC2A1/GLUT1 (PubMed:25136126).|||Belongs to the VPS26 family.|||Component of the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35 (PubMed:21040701, PubMed:21920005, PubMed:18088321, PubMed:20875039). The CSC has a highly elongated structure with VPS26 and VPS29 binding independently at opposite distal ends of VPS35 as central platform (Probable). The CSC is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants. The originally described SNX-BAR retromer is a pentamer containing the CSC and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. The CSC associates with SNX3 to form a SNX3-retromer complex. The CSC associates with SNX27, the WASH complex and the SNX-BAR subcomplex to form the SNX27-retromer complex (By similarity). Interacts with VPS29, VPS35, TBC1D5, GOLPH3, SNX27 (PubMed:16190980, PubMed:21040701, PubMed:21920005, PubMed:25136126).|||Cytoplasm|||Early endosome|||Late endosome|||Membrane|||Ubiquitously expressed in developing embryo and adult. Highly expressed in brain. http://togogenome.org/gene/10090:Mfsd4b1 ^@ http://purl.uniprot.org/uniprot/Q8VCV9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Belongs to the major facilitator superfamily.|||May function as a sodium-dependent glucose transporter. Potential channels for urea in the inner medulla of kidney. http://togogenome.org/gene/10090:Shb ^@ http://purl.uniprot.org/uniprot/Q6PD21 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components. May play a role in angiogenesis by regulating FGFR1, VEGFR2 and PDGFR signaling. May also play a role in T-cell antigen receptor/TCR signaling, interleukin-2 signaling, apoptosis and neuronal cells differentiation by mediating basic-FGF and NGF-induced signaling cascades. May also regulate IRS1 and IRS2 signaling in insulin-producing cells (By similarity).|||Cell membrane|||Cytoplasm|||Expressed in heart, liver, brain and kidney (at protein level).|||Interacts with phosphorylated 'Tyr-720' of the ligand-activated receptor PDGFRA via its SH2 domain. Interacts with the ligand-activated receptors PDGFRB, FGFR1, KDR/VEGFR2, IL2RB and IL2RG. Interacts with EPS8 and V-SRC. Interacts with GRB2 and GRAP. Interacts with CD3Z. Interacts with tyrosine-phosphorylated LAT upon T-cell antigen receptor activation. Interacts with PLCG1. Interacts with ZAP70, LCP2/SLP-76, VAV1 and GRAP2. Interacts with JAK1 and JAK3. Interacts with PTK2/FAK1. Interacts with CRK/CrKII. Interacts with IRS2 (By similarity). Interacts with PTPN11.|||Phosphorylated upon PDGFRA, PDGFRB, TCR, IL2 receptor, FGFR1 or VEGFR2 activation.|||The SH2 domain preferentially binds phosphopeptides with the consensus sequence Y-[TVI]-X-L and mediates interaction with PDGFRA, PDGFRB, FGRFR1, IL2RB, IL2RG, CD3Z and CRK/CrKII.|||Up-regulated by okadaic acid and genistein. http://togogenome.org/gene/10090:Acan ^@ http://purl.uniprot.org/uniprot/Q61282 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aggrecan/versican proteoglycan family.|||Contains mostly chondroitin sulfate, but also keratan sulfate chains, N-linked and O-linked oligosaccharides.|||Defects in Acan are the cause of cartilage matrix deficiency (CMD). CMD is an autosomal recessive syndrome characterized by cleft palate, short limbs, tail and snout. Mutation in strain CMD causes absence of aggrecan by truncation of the protein (mutation in the G1 domain).|||Expressed in chondrocytes throughout the developing skeleton in a pattern very similar but not identical to those of type II and IX collagen. In the newborn mouse skeleton it is expressed essentially in a mutually exclusive manner with tenascin, which is expressed osteoblasts, periosteal and perichondrial cells, and in cells at articular surfaces.|||Interacts with COMP (By similarity). Interacts with FBLN1.|||Specifically expressed in cartilage tissues.|||This proteoglycan is a major component of extracellular matrix of cartilagenous tissues. A major function of this protein is to resist compression in cartilage. It binds avidly to hyaluronic acid via an N-terminal globular region. May play a regulatory role in the matrix assembly of the cartilage.|||Two globular domains, G1 and G2, comprise the N-terminus of the proteoglycan, while another globular region, G3, makes up the C-terminus. G1 contains Link domains and thus consists of three disulfide-bonded loop structures designated as the A, B, B' motifs. G2 is similar to G1. The keratan sulfate (KS) and the chondroitin sulfate (CS) attachment domains lie between G2 and G3.|||extracellular matrix http://togogenome.org/gene/10090:Scrib ^@ http://purl.uniprot.org/uniprot/Q80U72 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LAP (LRR and PDZ) protein family.|||Cell junction|||Cell membrane|||Cytoplasm|||Expressed in CD4+ T-cells (at protein level) (PubMed:18329370). Found in a wide range of tissues including liver, kidney and spleen (PubMed:15806148). Also expressed in the brain (at protein level) (PubMed:15182672, PubMed:15806148).|||First detected at 7.5 dpc in the neuroepithelium at the time of initial neural tube closure. Also expressed in cranial mesenchyme, branchial arches, somitic mesoderm and lateral mesoderm. At later stages it is expressed in the eyelid epithelium, submandibular glands, whisker and hair follicles, sympathetic glanglia, inner ear, thymus, testis, kidney, esophagus, lung, stomach, trigeminal and dorsal root glanglia.|||Interacts with UBE3A (By similarity). Interacts with PAK1 and PAK2 (PubMed:18716323). Interacts (via PDZ domains) with VANGL2 (PubMed:16687519). Interacts (via PDZ domains) with LPP and TRIP6; the interaction is direct (By similarity). Interacts (via PDZ domains) with TJP2 (By similarity). Interacts (via PDZ domains) with APC; may mediate APC targeting to adherens junctions of epithelial cells (PubMed:16611247). Interacts (via PDZ domains) with TSHR; regulates TSHR trafficking and function (By similarity). Interacts with ARHGEF7 and GIT1; interacts directly with ARHGEF7 (PubMed:15182672). Interacts with CTNNB1 (PubMed:16611247, PubMed:19458197). Interacts with MAPK12 (PubMed:15878399). Interacts (via PDZ domains 1 and 3) with MCC (By similarity). Interacts with DLG5 (By similarity). Interacts with STK4/MST1 and LATS1 in the presence of DLG5 (By similarity). Interacts (via PDZ domain 3) with CRTAM (via PDZ-binding motif); the interaction promotes CRTAM and SCRIB polarization in a subset of CD4+ T-cells (PubMed:18329370).|||Palmitoylated. Could be depalmitoylated by LYPLA1 and/or LYPLA2. Palmitoylation of SCRIB by ZDHHC7 is required for its localization to cell-cell junctions, function in the establishement of epithelial cell polarity and the regulation of downstream signaling pathways important for epithelial cell differentiation.|||Postsynapse|||Presynapse|||Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:12499390, PubMed:18716323, PubMed:19041750, PubMed:18329370). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (PubMed:18329370). Most probably functions in the establishment of apico-basal cell polarity (PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:19041750). May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling (PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:19458197). Functions as an activator of Rac GTPase activity.|||The circletail (Crc) mice exhibit craniorachischisis, a severe form of neural tube defect. This is due to a single base insertion in the Scrib gene creating a frameshift which leads to synthesis of a truncated protein.|||Ubiquitinated; targeted for UBE3A-dependent multiubiquitination and degraded.|||adherens junction|||lamellipodium http://togogenome.org/gene/10090:Ptges ^@ http://purl.uniprot.org/uniprot/Q8BNP8|||http://purl.uniprot.org/uniprot/Q9JM51 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is increased markedly in macrophages and osteoblasts following pro-inflammatory stimuli.|||Belongs to the MAPEG family.|||Deficient mice are viable and fertile and develop normally (PubMed:12835414, PubMed:14566340). However mice display a marked reduction in inflammatory responses and reduced pain sensitivity (PubMed:12835414). PTGES deletion results in a reduction of PGE2 levels in the central nervous system in association with the impaired LPS-induced febrile response (PubMed:14566340).|||Homotrimer.|||Induced by pro-inflammatory stimuli and down-regulated by anti-inflammatory glucocorticoid.|||Membrane|||Terminal enzyme of the cyclooxygenase (COX)-2-mediated prostaglandin E2 (PGE2) biosynthetic pathway (PubMed:10869354, PubMed:11795891). Catalyzes the glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli (PubMed:11795891, PubMed:10869354). Plays a key role in inflammation response, fever and pain (PubMed:12835414, PubMed:14566340). Catalyzes also the oxidoreduction of endocannabinoids into prostaglandin glycerol esters and PGG2 into 15-hydroperoxy-PGE2. In addition, displays low glutathione transferase and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Ash2l ^@ http://purl.uniprot.org/uniprot/Q91X20 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Both monomethylated and dimethylated on arginine residues in the C-terminus. Arg-291 is the major site. Methylation is not required for nuclear localization, nor for MLL complex integrity or maintenance of global histone H3K4me3 levels (By similarity).|||Interacts with HCFC1 (By similarity). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (By similarity). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (By similarity). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (By similarity). Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5 (PubMed:21335234). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (By similarity). Within the complex, interacts with ZNF335 (By similarity). Interacts with RBBP5 (By similarity). Components of this complex may associate with components of a nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (By similarity). Within this complex also interacts with CCAR2 and EMSY (By similarity). Interacts with DPY30 (By similarity). Interacts with SETD1A and SETD1B (By similarity).|||Nucleus|||Transcriptional regulator (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (By similarity). Component of the Set1/Ash2 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3, but not if the neighboring 'Lys-9' residue is already methylated (By similarity). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (By similarity). May play a role in hematopoiesis (By similarity). In association with RBBP5 and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (By similarity).|||Ubiquitously expressed, with abundant expression in the heart, skeletal muscle and kidney. Low expression is seen in spleen, lung and testis. http://togogenome.org/gene/10090:Wbp2 ^@ http://purl.uniprot.org/uniprot/P97765 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation. In presence of estrogen, binds to ESR1-responsive promoters. Required for YAP1 coactivation function on PGR activity. Synergizes with WBP2 in enhancing PGR activity (By similarity). Modulates expression of post-synaptic scaffolding proteins via regulation of ESR1, ESR2 and PGR (PubMed:26881968).|||Binds to the WW domain of YAP1, WWP1 and WWP2 (By similarity) (PubMed:7644498). Interacts with NEDD4 (PubMed:11042109). Interacts with ESR1 and UBE3A (By similarity).|||Cytoplasm|||Expressed in the ear and the eye (PubMed:26881968). Isoform 1 is expressed in brain, inner ear and organ of Corti. Isoform 2 is only detected in brain (PubMed:26881968).|||Mutant animals have a progressive high-frequency hearing loss (PubMed:26881968). They show swelling of afferent terminals and abnormal expression of AMPA receptor subunit at post-synaptic densities (PubMed:26881968). Mice are fertile and show no other abnormalities (PubMed:26881968).|||Nucleus|||Phosphorylated in repsonse to EGF as well as estrogen and progesterone hormones. Tyr-192 and Tyr-231 are phosphorylated by YES and SRC inducing nuclear translocation.|||The PPxY motif 1 mediates interaction with NEDD4 (PubMed:11042109). The PPxY motif 2 is required for the coactivation function (By similarity). http://togogenome.org/gene/10090:Or6c8 ^@ http://purl.uniprot.org/uniprot/Q8VG33 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kiz ^@ http://purl.uniprot.org/uniprot/Q3UXL4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the kizuna family.|||Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole.|||Interacts with AKAP9, CEP72, ODF2, PCNT and TUBGCP2.|||Phosphorylation at Thr-391 by PLK1 is not needed for centrosomal localization or pericentriolar material expansion but is indispensable for spindle-pole stabilization.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Ercc6l2 ^@ http://purl.uniprot.org/uniprot/Q9JIM3 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Interacts with NEK6.|||May be involved in early DNA damage response.|||Mitochondrion|||Nucleus|||Phosphorylated by NEK6.|||The first 10 codons may be found on an alternative exon not observed on any other cDNA/EST.|||centrosome http://togogenome.org/gene/10090:Or14j6 ^@ http://purl.uniprot.org/uniprot/Q8VF25 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chrna2 ^@ http://purl.uniprot.org/uniprot/Q91X60 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-2/CHRNA2 sub-subfamily.|||Cell membrane|||Neuronal AChR seems to be composed of two different types of subunits: alpha and non-alpha (beta). Alpha-2 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors. The alpha-2:beta-2 nAChR complex is proposed to be a heteropentamer with two subtypes: LS (low agonist sensitivity) with a (alpha-2)3:(beta-2)2 and HS (high agonist sensitivity) with a (alpha-2)2:(beta-2)3 stoichiometry; the subtypes differ in their subunit binding interfaces which are involved in ligand binding (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Ehd2 ^@ http://purl.uniprot.org/uniprot/Q8BH64 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis (PubMed:24508342). Plays a role in membrane trafficking between the plasma membrane and endosomes. Important for the internalization of GLUT4 (PubMed:14676205). Required for fusion of myoblasts to skeletal muscle myotubes. Required for normal translocation of FER1L5 to the plasma membrane (PubMed:18502764, PubMed:21177873). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by constraining caveolae at the cell membrane (By similarity).|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.|||Cell membrane|||Detected in lung and adipocytes. Detected at lower levels in heart and skeletal muscle.|||Endosome membrane|||Homodimer and homooligomer (By similarity). Interacts with EHD1 (By similarity). May also interact with EHD3 and EHD4 (By similarity). Interacts with MYOF (PubMed:18502764, PubMed:21177873). Interacts with EHBP1 (PubMed:14676205). Interacts with FER1L5 (via second C2 domain) (PubMed:21177873). Interacts with CAV1 in a cholesterol-dependent manner (By similarity). Interacts (via EH domain) with PACSIN2 (via NPF motifs); this interaction probably stabilizes the caveolae (By similarity).|||The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.|||The very low intrinsic ATPase activity is increased upon interaction with liposomes.|||caveola|||cytosol http://togogenome.org/gene/10090:Txndc9 ^@ http://purl.uniprot.org/uniprot/Q9CQ79 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis, liver, heart, kidney, brain, spleen and lung.|||Forms ternary complexes with the chaperonin TCP1 complex, spanning the cylindrical chaperonin cavity and contacting at least 2 subunits.|||Midbody|||Nucleus|||Significantly diminishes the chaperonin TCP1 complex ATPase activity, thus negatively impacts protein folding, including that of actin or tubulin.|||centrosome http://togogenome.org/gene/10090:Apeh ^@ http://purl.uniprot.org/uniprot/Q8R146 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S9C family.|||Cytoplasm|||Homotetramer.|||Homotetramerization is required for activity. Tetramerization results in the formation of a gated channel which is involved in substrate selection and substrate access to the catalytic sites.|||This enzyme catalyzes the hydrolysis of the N-terminal peptide bond of an N-acetylated peptide to generate an N-acetylated amino acid and a peptide with a free N-terminus (By similarity). It preferentially cleaves off Ac-Ala, Ac-Met and Ac-Ser (By similarity). Also, involved in the degradation of oxidized and glycated proteins (By similarity). http://togogenome.org/gene/10090:Adgre5 ^@ http://purl.uniprot.org/uniprot/A0A0D9SEG8|||http://purl.uniprot.org/uniprot/E9QJS7|||http://purl.uniprot.org/uniprot/E9QMJ5|||http://purl.uniprot.org/uniprot/Q9DC42|||http://purl.uniprot.org/uniprot/Q9Z0M6 ^@ Caution|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although predominantly expressed by cells of the immune system, expressed ubiquitously with particularly high levels of expression in the lung and the thymus gland. In the spleen, expression is detected on most myeloid cells and variable portions of T-cells, B-cells and NK cells. In the bone marrow, expressed in nearly all myeloid cells, whereas little if any expression is found on erythroid cells.|||Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Binding to chondroitin sulfate is mediated by the fourth EGF domain.|||Cell membrane|||Forms a heterodimer, consisting of a large extracellular region (alpha subunit) non-covalently linked to a seven-transmembrane moiety (beta subunit). Interacts with complement decay-accelerating factor (DAF). The largest isoform (isoform 1) do not interact with DAF. Interacts also with chondroitin sulfate (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Proteolytically cleaved into 2 subunits, an extracellular alpha subunit and a seven-transmembrane subunit.|||Receptor potentially involved in both adhesion and signaling processes early after leukocyte activation. Plays an essential role in leukocyte migration.|||The first two EGF domains mediate the interaction with DAF. A third tandemly arranged EGF domain is necessary for the structural integrity of the binding region (By similarity).|||Up-regulated during lymphocyte activation.|||extracellular space http://togogenome.org/gene/10090:Lce3e ^@ http://purl.uniprot.org/uniprot/F8VQJ0 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Skor2 ^@ http://purl.uniprot.org/uniprot/A7M7C7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a TGF-beta antagonist in the nervous system (By similarity). Exhibits transcriptional repressor activity.|||Belongs to the SKI family.|||Cytoplasm|||Expression is restricted to adult and embryonic central nervous system. Expressed at high levels in the developing cerebellum, ventral metencephalon and myelencephalon at 12.5 dpc (at protein level). In the adult cerebellum, expressed specifically in Purkinje cells.|||First detected at 11 dpc and expression continues into adulthood with higher levels in embryonic than adult brain. In developing brain, not expressed in neural progenitors during the proliferative phase but expression is detected in postmitotic neural precursors shortly after exiting the cell cycle.|||Interacts with SMAD2 and SMAD3.|||Nucleus http://togogenome.org/gene/10090:Myrip ^@ http://purl.uniprot.org/uniprot/Q8K3I4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds RAB27A that has been activated by GTP-binding via its N-terminus. Binds MYO5A, MYO7A and F-actin. Interacts with PRKAR2A. Interacts with components of the exocyst complex, including EXOC3 and EXOC4.|||Cytoplasm|||Detected in brain, skin, heart, lung, adrenal medulla, pancreas, intestine, liver, kidney, skeletal muscle and testis. Detected in cochlear and vestibular hair cells in the inner ear, and in photoreceptor and pigment epithelium cells in the retina.|||Melanosome|||Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor proteins MYO5A and MYO7A. May link RAB27A-containing vesicles to actin filaments. Functions as a protein kinase A-anchoring protein (AKAP). May act as a scaffolding protein that links PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release.|||perinuclear region|||secretory vesicle http://togogenome.org/gene/10090:Oog1 ^@ http://purl.uniprot.org/uniprot/E9Q5G7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRAME family.|||Cytoplasm|||Expressed in the ovary, ovulated oocytes and preimplantation embryos (at protein level). Not detected in testis, liver, kidney, spleen, heart, lung and brain.|||Expressed predominantly in oocytes and one- to four-cell-stage embryos with weak expression in morula/blastocyst-stage embryos (at protein level). Expression increases from oocyte to the one-cell stage and then decreases toward the four-cell stage (at protein level). Highly expressed in oocytes of primary, secondary and antral follicles with low levels in oocytes of primordial follicles (at protein level).|||Expression of spermatogenesis-associated genes including Klhl10, Tekt2, Tdrd6 and Tnp2 are significantly up-regulated in the ovaries.|||Interacts with RALGDS (via Ras-associating domain) (PubMed:16580637). Interacts with HRAS (in GTP-bound form) (PubMed:16580637).|||May down-regulate the expression of spermatogenesis-associated genes in female germ cells allowing their normal differentiation into oocytes (PubMed:29731491). May act as a Ras-mediated signaling protein in early embryogenesis.|||Nucleus http://togogenome.org/gene/10090:Hmgcll1 ^@ http://purl.uniprot.org/uniprot/Q8JZS7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HMG-CoA lyase family.|||Endoplasmic reticulum membrane|||Non-mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis, the products of which support energy production in nonhepatic animal tissues.|||cytosol http://togogenome.org/gene/10090:Sh2b2 ^@ http://purl.uniprot.org/uniprot/Q9JID9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3 (By similarity).|||Belongs to the SH2B adapter family.|||Cell membrane|||Cytoplasm|||Homodimer. Interacts with KIT/c-KIT, SHC1, EPOR, PDGFR, VAV1 and VAV3. Interacts (via N-terminal region) with SHC1. Interacts (via the phosphorylated C-terminus) with GRB2. Interacts (via its SH2 domain) with EPOR, INSR and KIT. Interacts with GRB2 after B-cell antigen receptor stimulation. Interacts (via PH domain) with VAV3. Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated); after stimulation of the receptor by its extracellular ligand and subsequent autophosphorylation of the receptor. Binds INSR, GRB2, ASB6 and CAP. Insulin stimulation leads to dissociation of CAP. Binds CBS only when SH2B2/APS has become phosphorylated. INSR binding does not depend on the phosphorylation of SH2B2/APS (By similarity).|||Strongly expressed in brain; also expressed in spleen, kidney and skeletal muscle, and at low levels in small intestine and bone marrow. Strongly expressed in B-cell lines, but not T-cell lines. Also expressed in myeloid and fibroblast cell lines.|||Tyrosine phosphorylated by JAK2, KIT and other kinases activated by B-cell receptor in response to stimulation with cytokines, IL3, IL5, PDGF, IGF1, IGF2, CSF2/GM-CSF and cross-linking of the B-cell receptor complex. http://togogenome.org/gene/10090:Vamp5 ^@ http://purl.uniprot.org/uniprot/Q5M9K2|||http://purl.uniprot.org/uniprot/Q791P0|||http://purl.uniprot.org/uniprot/Q9Z2P8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the synaptobrevin family.|||Cell membrane|||During myogenesis.|||Endomembrane system|||May participate in trafficking events that are associated with myogenesis, such as myoblast fusion and/or GLUT4 trafficking.|||Membrane|||Preferentially expressed in the skeletal muscle and heart, detected at lower levels in several other tissues but not in the brain.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Loxl2 ^@ http://purl.uniprot.org/uniprot/P58022 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lysyl oxidase family.|||Chromosome|||Component of some chromatin repressor complex. Interacts with SNAI1. Interacts with TAF10. Interacts with HSPA5. Interacts with EFEMP2 (By similarity).|||Contains 1 lysine tyrosylquinone.|||Endoplasmic reticulum|||Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (By similarity). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (By similarity). Shows no activity against histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated (H3K4me2) (By similarity). Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription (By similarity). LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2 (PubMed:25959397). Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin, probably by mediating deamination of histone H3 (By similarity). During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription (By similarity). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (By similarity). Interacts with the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 pathway of the unfolded protein response, leading to expression of several transcription factors involved in EMT and subsequent EMT induction (By similarity). When secreted into the extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (By similarity). Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (By similarity). Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (PubMed:21071451).|||N-glycosylated. N-glycosylation on Asn-458 and Asn-646 may be essential for proper folding and secretion; may be composed of a fucosylated carbohydrates attached to a trimannose N-linked glycan core.|||Nucleus|||Specifically inhibited by a mouse monoclonal antibody AB0023, inhibition occurs in a non-competitive manner.|||Strongly induced in hypoxia.|||The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.|||Ubiquitous. Highest expression in skin, lung and thymus. Present in chondrocytes: mainly expressed by chondrocytes in healing fractures and in epiphyseal growth plates (at protein level).|||basement membrane http://togogenome.org/gene/10090:Lamb1 ^@ http://purl.uniprot.org/uniprot/E9QN70|||http://purl.uniprot.org/uniprot/P02469|||http://purl.uniprot.org/uniprot/Q3UHL7 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Involved in the organization of the laminar architecture of the cerebral cortex (By similarity). It is probably required for the integrity of the basement membrane/glia limitans that serves as an anchor point for the endfeet of radial glial cells and as a physical barrier to migrating neurons (By similarity). Radial glial cells play a central role in cerebral cortical development, where they act both as the proliferative unit of the cerebral cortex and a scaffold for neurons migrating toward the pial surface (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Beta-1 is a subunit of laminin-1 (laminin-111 or EHS laminin), laminin-2 (laminin-211 or merosin), laminin-6 (laminin-311 or K-laminin), laminin-8 (laminin-411), laminin-10 (laminin-511) and laminin-12 (laminin-213) (By similarity). Interacts with ITGB1 (PubMed:34427057).|||Membrane|||Widely expressed in the embryo. High levels are detected in the cerebellar basement membrane, at postnatal day 7.|||basement membrane http://togogenome.org/gene/10090:Or4k52 ^@ http://purl.uniprot.org/uniprot/Q8VGE9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r214 ^@ http://purl.uniprot.org/uniprot/Q8R279 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plk1 ^@ http://purl.uniprot.org/uniprot/Q07832|||http://purl.uniprot.org/uniprot/Q3TPZ2 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation of Thr-210 by AURKA; phosphorylation by AURKA is enhanced by BORA. Once activated, activity is stimulated by binding target proteins. Binding of target proteins has no effect on the non-activated kinase. Several inhibitors targeting PLKs are currently in development and are under investigation in a growing number of clinical trials, such as BI 2536, an ATP-competitive PLK1 inhibitor or BI 6727, a dihydropteridinone that specifically inhibits the catalytic activity of PLK1 (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.|||Catalytic activity is enhanced by phosphorylation of Thr-210. Phosphorylation at Thr-210 is first detected on centrosomes in the G2 phase of the cell cycle, peaks in prometaphase and gradually disappears from centrosomes during anaphase. Dephosphorylation at Thr-210 at centrosomes is probably mediated by protein phosphatase 1C (PP1C), via interaction with PPP1R12A/MYPT1. Autophosphorylation and phosphorylation of Ser-137 may not be significant for the activation of PLK1 during mitosis, but may enhance catalytic activity during recovery after DNA damage checkpoint. Phosphorylated in vitro by STK10 (By similarity).|||In the thymus, levels increased during fetal development, were highest in newborn animals and decreased in the adult. In the testes, the PLK levels were higher in the adult than in prepubescent mice while in the ovary, the levels were higher in the prepubescent mice. Accumulates to a maximum during the G2 and M phases, declines to a nearly undetectable level following mitosis and throughout G1 phase, and then begins to accumulate again during S phase.|||Interacts with CEP170 and EVI5. Interacts and phosphorylates ERCC6L. Interacts with FAM29A. Interacts with SLX4/BTBD12 and TTDN1. Interacts with BUB1B. Interacts (via POLO-box domain) with the phosphorylated form of BUB1, CENPU and CDC25C. Interacts with isoform 3 of SGO1. Interacts with BORA, KIF2A and AURKA. Interacts with TOPORS and CYLD. Interacts with ECT2; the interaction is stimulated upon phosphorylation of ECT2 on 'Thr-444'. Interacts with PRC1. Interacts with KIF20A/MKLP2 (when phosphorylated), leading to the recruitment at the central spindle. Interacts (via POLO box domains) with PPP1R12A/MYPT1 (when previously phosphorylated by CDK1) (By similarity). Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2 (By similarity). Interacts with BIRC6/bruce (By similarity). Interacts with CDK1-phosphorylated DCTN6 during mitotic prometaphase; the interaction facilitates recruitment to kinetochores (By similarity). Interacts with CDK1-phosphorylated FRY; this interaction occurs in mitotic cells, but not in interphase cells. FRY interaction facilitates AURKA-mediated PLK1 phosphorylation. Interacts with CEP68; the interaction phosphorylates CEP68. Interacts (via POLO-box domain) with DCTN1 (By similarity). Interacts with CEP20 in later G1, S, G2 and M phases of the cell cycle; this interaction recruits PLK1 to centrosomes, a step required for S phase progression (By similarity). Interacts with HSF1; this interaction increases upon heat shock but does not modulate neither HSF1 homotrimerization nor DNA-binding activities (By similarity). Interacts with HNRNPU; this interaction induces phosphorylation of HNRNPU in mitosis (By similarity). Interacts (via its N-terminus) with RIOK2 (By similarity). Interacts with KLHL22 (By similarity). Interacts (via POLO box domains) with NEDD9/HEF1 (via C-terminus) (PubMed:29191835). Interacts (via RVxF motif) with FIRRM; regulates PLK1 kinase activity (By similarity).|||Lethality: homozygous embryos do not develop beyond the eight cell stage. Heterozygous mice are healthy and fertile but frequently develop tumors, most frequently lung-invading and liver-invading lymphomas. Analysis of chromosome spreads of spleen-derived cells from 6-month-old mice show aneuploidy.|||Midbody|||Newborn and adult spleen, fetal and newborn kidney, liver, brain, thymus and adult bone marrow, thymus, ovary and testes.|||Nucleus|||Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis.Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (By similarity). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (PubMed:25533956). Phosphorylates CEP68 and is required for its degradation. Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (By similarity). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (By similarity). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (By similarity). Regulates mitotic progression by phosphorylating RIOK2 (By similarity). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967).|||The POLO box domains act as phosphopeptide-binding module that recognize and bind serine-[phosphothreonine/phosphoserine]-(proline/X) motifs. PLK1 recognizes and binds docking proteins that are already phosphorylated on these motifs, and then phosphorylates them. PLK1 can also create its own docking sites by mediating phosphorylation of serine-[phosphothreonine/phosphoserine]-(proline/X) motifs subsequently recognized by the POLO box domains (By similarity).|||Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in anaphase and following DNA damage, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Ubiquitination and subsequent degradation prevents entry into mitosis and is essential to maintain an efficient G2 DNA damage checkpoint. Monoubiquitination at Lys-492 by the BCR(KLHL22) ubiquitin ligase complex does not lead to degradation: it promotes PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (By similarity).|||centrosome|||kinetochore|||spindle http://togogenome.org/gene/10090:Trip6 ^@ http://purl.uniprot.org/uniprot/Q9Z1Y4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zyxin/ajuba family.|||Cytoplasm|||Expressed throughout development in all embryonic stages analyzed, 10.5 days post coitum (dpc) to 18.5 dpc. In 16.5 dpc embryos highly expressed in skin, lung, thymus, duodenum and the ependymal cell layer surrounding the ventricles in brain. Highly expressed also in the salivary glands, tongue, vibrissae, choroid plexus, blood vessel walls, esophagus and midgut. Low expression levels in spinal cord, heart and liver.|||Highly expressed in kidney, stomach, lung, heart and testis. Low expression levels in brain, colon, thymus, pancreas and skin. Not expressed in skeletal muscle.|||Nucleus|||Phosphorylation at Tyr-55 by SRC is required for enhancement of lysophosphatidic acid-induced cell migration. Tyr-55 is dephosphorylated by PTPN13 (By similarity).|||Relays signals from the cell surface to the nucleus to weaken adherens junction and promote actin cytoskeleton reorganization and cell invasiveness. Involved in lysophosphatidic acid-induced cell adhesion and migration. Acts as a transcriptional coactivator for NF-kappa-B and JUN, and mediates the transrepression of these transcription factors induced by glucocorticoid receptor (By similarity).|||Specifically interacts with the ligand binding domain of the thyroid receptor (TR) in the presence of thyroid hormone (By similarity). Interacts (via the third LIM domain and C-terminus) with PTPN13 (via the second PDZ domain). Interacts (via the second LIM domain or via the third LIM domain plus C-terminus) with PDLIM4 (via PDZ domain). Found in a complex with PTPN13 and PDLIM4 (PubMed:10826496). Interacts with SVIL isoform 2. Interacts with LPAR2 but not other LPA receptors. Interacts with PRKAA2. Interacts with MAGI1. Interacts with SCRIB (By similarity). In case of infection, interacts with S.typhimurium protein sseI (PubMed:17095609).|||The LIM zinc-binding domains mediate interaction with LPAR2.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Pde11a ^@ http://purl.uniprot.org/uniprot/P0C1Q2 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cyclic nucleotide phosphodiesterase family.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Expressed in testis and developing spermatoza.|||Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator (By similarity).|||Mice live well and have no impaired fertility. They do however display reduced sperm concentration, rate of forward progression and percentage of live spermatozoa. Pre-ejaculated sperm display increased premature/spontaneous capacitance.|||Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP (PubMed:15800654). Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively (By similarity).|||The tandem GAF domains bind cGMP, and regulate enzyme activity. The binding of cGMP stimulates enzyme activity.|||cytosol http://togogenome.org/gene/10090:Plod2 ^@ http://purl.uniprot.org/uniprot/E9Q718|||http://purl.uniprot.org/uniprot/Q9R0B9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.|||Homodimer.|||Is highly expressed in the heart, lung, kidney, eye, ovary and placenta.|||Rough endoplasmic reticulum membrane http://togogenome.org/gene/10090:Saa1 ^@ http://purl.uniprot.org/uniprot/P05366|||http://purl.uniprot.org/uniprot/Q5I0U6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAA family.|||By bacterial lipopolysaccharide.|||Detected in blood plasma (at protein level). Detected in liver.|||Homohexamer; dimer of trimers. Can form amyloid fibrils after partial proteolysis; the native, undenatured protein does not form amyloid fibrils (in vitro). Apolipoprotein of the HDL complex. Binds to heparin (By similarity).|||Major acute phase protein.|||Major acute phase reactant. Apolipoprotein of the HDL complex.|||Secreted http://togogenome.org/gene/10090:Irgm2 ^@ http://purl.uniprot.org/uniprot/A0A140LIF8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.|||Cytoplasmic vesicle membrane|||Golgi apparatus membrane|||Immunity-related GTPase that plays important roles in innate immunity and inflammatory response (PubMed:17641048, PubMed:33124769, PubMed:33124745, PubMed:34338548, PubMed:34078740). Acts as a dynamin-like protein that binds to intracellular membranes and promotes remodeling and trafficking of those membranes (By similarity). Required for clearance of acute protozoan and bacterial infections (PubMed:17641048, PubMed:34338548, PubMed:34078740). Acts by participating to Tgtp1/Irgb6 and Gbp1-mediated parasite killing by promoting their accumulation on the T.gondii parasitophorous vacuole membranes (PubMed:34078740). Also required for prolonged loading of ubiquitin and p62/Sqstm1 to parasitophorous vacuole membranes (PubMed:34078740). Also acts as a key negative regulator of the inflammatory response by inhibiting the non-canonical inflammasome, thereby protecting against Casp11-driven septic shock during endotoxemia (PubMed:33124769, PubMed:33124745).|||Mice are highly susceptible to T.gondii infection, due to impaired ability to mediate clearance of acute protozoan infections (PubMed:34078740, PubMed:34338548). They also display strongly increased activation of the Casp11-dependent inflammatory responses when exposed to extracellular lipopolysaccharide (LPS), bacterial outer membrane vesicles or Gram-negative bacteria (PubMed:33124745). Mice lacking Irgm1, Irgm2 and Igtp/Irgm3 (panIrgm mice) show resistance against M.tuberculosis one month post-infection; then, panIrgm mice display higher bacterial burden and altered cytokine during late stage of infection, leading to increased mortality (PubMed:36629440).|||Ubiquitinated; polyubiquitinated in the cytosol, promoting Gbp1 recruitment to the T.gondii parasitophorous vacuole membranes.|||cytosol http://togogenome.org/gene/10090:Tmem270 ^@ http://purl.uniprot.org/uniprot/Q6UJB9 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Membrane|||Testis. http://togogenome.org/gene/10090:Abat ^@ http://purl.uniprot.org/uniprot/P61922 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.|||Binds 1 [2Fe-2S] cluster per homodimer.|||Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.|||Homodimer; disulfide-linked.|||Mitochondrion matrix http://togogenome.org/gene/10090:Or5ap2 ^@ http://purl.uniprot.org/uniprot/Q8VFK7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Serpinb8 ^@ http://purl.uniprot.org/uniprot/O08800|||http://purl.uniprot.org/uniprot/Q8C871 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Has an important role in epithelial desmosome-mediated cell-cell adhesion. http://togogenome.org/gene/10090:Rft1 ^@ http://purl.uniprot.org/uniprot/Q8C3B8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RFT1 family.|||May be involved in N-linked oligosaccharide assembly. May participate in the translocation of oligosaccharide from the cytoplasmic side to the lumenal side of the endoplasmic reticulum membrane (By similarity).|||Membrane http://togogenome.org/gene/10090:Col6a5 ^@ http://purl.uniprot.org/uniprot/A6H584 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type VI collagen family.|||Collagen VI acts as a cell-binding protein.|||In newborn, it is expressed in lung, heart, kidney, muscle, brain, intestine, skin, femur, sternum and calvaria. In adult, it is widely expressed and is detected in lung, heart, kidney, spleen, muscle, ovary, uterus, brain, skin, liver and sternum.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-4(VI) or alpha-5(VI) or alpha-6(VI).|||extracellular matrix http://togogenome.org/gene/10090:Scnn1g ^@ http://purl.uniprot.org/uniprot/Q9WU39 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by WNK1, WNK2, WNK3 and WNK4.|||Apical cell membrane|||Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1G subfamily.|||ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation.|||Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (Probable). Interacts with NEDD4; via the WW domains (PubMed:11244092, PubMed:15123669). Interacts with NEDD4L; via the WW domains (PubMed:12424229, PubMed:11244092, PubMed:15123669). Interacts with WWP1; via the WW domains (By similarity). Interacts with WWP2; via the WW domains. Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (By similarity).|||Lung and kidney.|||Phosphorylated on serine and threonine residues. Aldosterone and insulin increase the basal level of phosphorylation.|||Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.|||Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation. http://togogenome.org/gene/10090:Cops3 ^@ http://purl.uniprot.org/uniprot/O88543 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CSN3 family.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2 (By similarity). The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases (By similarity). CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively (By similarity). Essential to maintain the survival of epiblast cells and thus the development of the postimplantation embryo (PubMed:12972600).|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS1, COPS4, COPS8 and COPS9 (By similarity). Interacts with CK2 and PKD (By similarity). Interacts with the translation initiation factor EIF3S6 and IKBKG (By similarity). Interacts with ERCC6 (By similarity).|||Cytoplasm|||Embryos arrest after 5.5 dpc and resorb by 8.5 dpc mainly due to increased cell death.|||Nucleus|||Widely expressed. http://togogenome.org/gene/10090:Osbp2 ^@ http://purl.uniprot.org/uniprot/Q5QNQ6|||http://purl.uniprot.org/uniprot/Q6PE09|||http://purl.uniprot.org/uniprot/Q8K0C7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the OSBP family.|||Binds 7-ketocholesterol.|||Membrane http://togogenome.org/gene/10090:Vmn2r61 ^@ http://purl.uniprot.org/uniprot/L7N2B8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Hif1a ^@ http://purl.uniprot.org/uniprot/A0A0R4J1E9|||http://purl.uniprot.org/uniprot/Q3UCW2|||http://purl.uniprot.org/uniprot/Q61221 ^@ Activity Regulation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of Lys-545 by ARD1 increases interaction with VHL and stimulates subsequent proteasomal degradation (By similarity). Deacetylation of Lys-719 by SIRT2 increases its interaction with and hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing its proteasomal degradation (By similarity).|||Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID) (By similarity).|||Cytoplasm|||Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:15225651, PubMed:17981124, PubMed:22009797). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:15225651, PubMed:17981124, PubMed:22009797). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (By similarity).|||In normoxia, is hydroxylated on Pro-402 and Pro-577 in the oxygen-dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1. EGLN3/PHD3 has also been shown to hydroxylate Pro-577. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Deubiquitinated by USP20. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). In normoxia, is hydroxylated on Asn-813 by HIF1AN, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Repressed by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated hydroxylation and subsequent proteasomal degradation.|||Induced by reactive oxygen species (ROS).|||Interacts with the ARNT; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Interacts with COPS5; the interaction increases the transcriptional activity of HIF1A through increased stability (PubMed:11707426). Interacts with EP300 (via TAZ-type 1 domains); the interaction is stimulated in response to hypoxia and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1 domains). Interacts with NCOA1, NCOA2, APEX1 and HSP90. Interacts (hydroxylated within the ODD domain) with VHLL (via beta domain); the interaction, leads to polyubiquitination and subsequent HIF1A proteasomal degradation. During hypoxia, sumoylated HIF1A also binds VHL; the interaction promotes the ubiquitination of HIF1A (By similarity). Interacts with SENP1; the interaction desumoylates HIF1A resulting in stabilization and activation of transcription (PubMed:17981124). Interacts (via the ODD domain) with NAA10; the interaction appears not to acetylate HIF1A nor have any affect on protein stability, during hypoxia. Interacts with RWDD3; the interaction enhances HIF1A sumoylation (By similarity). Interacts with TSGA10 (PubMed:16777103). Interacts with HIF3A (PubMed:21546903). Interacts with RORA (via the DNA binding domain); the interaction enhances HIF1A transcription under hypoxia through increasing protein stability. Interaction with PSMA7 inhibits the transactivation activity of HIF1A under both normoxic and hypoxia-mimicking conditions. Interacts with USP20. Interacts with RACK1; promotes HIF1A ubiquitination and proteasome-mediated degradation. Interacts (via N-terminus) with USP19. Interacts with SIRT2. Interacts (deacetylated form) with EGLN1. Interacts with CBFA2T3. Interacts with HSP90AA1 and HSP90AB1. Interacts with DCUN1D1; this interaction increases the interaction between VHL and DCUN1D1. Interacts with HIF1AN (By similarity).|||Nucleus|||Nucleus speckle|||Requires phosphorylation for DNA-binding. Phosphorylation at Ser-247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding (By similarity). Phosphorylation by GSK3-beta and PLK3 promote degradation by the proteasome (PubMed:20889502).|||S-nitrosylation of Cys-810 may be responsible for increased recruitment of p300 coactivator necessary for transcriptional activity of HIF-1 complex.|||Sumoylated; with SUMO1 under hypoxia (PubMed:15225651, PubMed:17981124). Sumoylation is enhanced through interaction with RWDD3 (By similarity). Both sumoylation and desumoylation seem to be involved in the regulation of its stability during hypoxia (PubMed:15225651, PubMed:17981124). Sumoylation can promote either its stabilization or its VHL-dependent degradation by promoting hydroxyproline-independent HIF1A-VHL complex binding, thus leading to HIF1A ubiquitination and proteasomal degradation (By similarity). Desumoylation by SENP1 increases its stability amd transcriptional activity (PubMed:17981124). There is a disaccord between various publications on the effect of sumoylation and desumoylation on its stability and transcriptional activity (Probable).|||The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.|||Ubiquitinated; in normoxia, following hydroxylation and interaction with VHL. Lys-545 appears to be the principal site of ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination through preventing hydroxylation at Asn-813. Ubiquitinated by E3 ligase VHL. Deubiquitinated by UCHL1 (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Scgb2b15 ^@ http://purl.uniprot.org/uniprot/A0A089N3E7|||http://purl.uniprot.org/uniprot/S4R2V3 ^@ Similarity ^@ Belongs to the secretoglobin family. http://togogenome.org/gene/10090:Tmem260 ^@ http://purl.uniprot.org/uniprot/Q8BMD6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 117 (GT117) family.|||Endoplasmic reticulum membrane|||O-mannosyl-transferase that transfers mannosyl residues to the hydroxyl group of serine or threonine residues of proteins. Specifically glycosylates the IPT/TIG domain of target proteins, such as MET and MST1R/RON. TMEM260-mediated O-mannosylated residues are composed of single mannose glycans that are not elongated or modified.|||Receptor maturation defects and abnormal epithelial morphogenesis. http://togogenome.org/gene/10090:Ifi214 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1R5|||http://purl.uniprot.org/uniprot/Q504N7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the HIN-200 family.|||Nucleus http://togogenome.org/gene/10090:Or9r7 ^@ http://purl.uniprot.org/uniprot/Q8VFU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ier3 ^@ http://purl.uniprot.org/uniprot/P46694 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IER3 family.|||By serum growth factors and TPA.|||Expressed predominantly in the lung, testes and the uterus.|||Glycosylated.|||Interacts with the PPP2R5C-PP2A holoenzyme and ERK kinases; regulates ERK dephosphorylation.|||May play a role in the ERK signaling pathway by inhibiting the dephosphorylation of ERK by phosphatase PP2A-PPP2R5C holoenzyme. Acts also as an ERK downstream effector mediating survival (By similarity). As a member of the NUPR1/RELB/IER3 survival pathway, may allow the development of pancreatic intraepithelial neoplasias.|||Membrane http://togogenome.org/gene/10090:H1f2 ^@ http://purl.uniprot.org/uniprot/P15864|||http://purl.uniprot.org/uniprot/Q5SZA3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated on Ser-187 in response to DNA damage.|||Belongs to the histone H1/H5 family.|||Chromosome|||Citrullination at Arg-54 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter.|||Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Interacts with TSC22D1 isoform 2.|||No visible phenotype. Triple-deficient mice (H1-2, H1-3 and H1-4) die by midgestation with a broad range of defects. These embryos have about 50% of the normal ratio of H1 to nucleosomes, demonstrating that critical levels of total H1 histones are essential for mouse embryogenesis.|||Nucleus|||The C-terminal domain is required for high-affinity binding to chromatin. http://togogenome.org/gene/10090:Vmn2r112 ^@ http://purl.uniprot.org/uniprot/L7N221 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnft1 ^@ http://purl.uniprot.org/uniprot/Q9DCN7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis.|||Early endosome membrane|||Expression in testis already detected at postnatal day 1 (P1), progressively increases with adult levels reached at P20.|||Predominantly expressed in testis. http://togogenome.org/gene/10090:Ptgfrn ^@ http://purl.uniprot.org/uniprot/Q9WV91 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Expressed in myoblasts (at protein level).|||Inhibits the binding of prostaglandin F2-alpha (PGF2-alpha) to its specific FP receptor, by decreasing the receptor number rather than the affinity constant. Functional coupling with the prostaglandin F2-alpha receptor seems to occur (By similarity). In myoblasts, associates with tetraspanins CD9 and CD81 to prevent myotube fusion during muscle regeneration.|||Interacts with CD9 and CD81 (By similarity). Part of a complex composed of CD9, CD81 and IGSF8 (PubMed:23575678). Also seems to interact with CD63, CD82 and CD151 (By similarity).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ece2 ^@ http://purl.uniprot.org/uniprot/B2RQR8|||http://purl.uniprot.org/uniprot/Q80Z57|||http://purl.uniprot.org/uniprot/Q80Z58 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M13 family.|||Binds 1 zinc ion per subunit.|||Converts big endothelin-1 to endothelin-1. Also involved in the processing of various neuroendocrine peptides, including neurotensin, angiotensin I, substance P, proenkephalin-derived peptides, and prodynorphin-derived peptides (By similarity). May play a role in amyloid-beta processing (PubMed:12464614).|||Eef1akmt4-Ece2 and Ece2 double mutant mice are fertile and healthy, and do not display any abnormality in terms of growth or aging.|||Golgi apparatus membrane|||Membrane|||secretory vesicle membrane http://togogenome.org/gene/10090:Smarcd1 ^@ http://purl.uniprot.org/uniprot/Q61466|||http://purl.uniprot.org/uniprot/Q68FH8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMARCD family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B), and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (PubMed:8804307, PubMed:8895581). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (ACTB) (By similarity). Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). Specifically interacts with the VDR heterodimer complex. Interacts with ESR1, NR3C1, NR1H4, PGR, SMARCA4, SMARCC1 and SMARCC2 (By similarity). Interacts with DPF2 (By similarity). Interacts with DPF3a (isoform 2 of DPF3/BAF45C) and with HDGFL2 in a DPF3a-dependent manner (By similarity). Interacts with FOS, FOSB isoform 1 and 2, FOSL1 and FOSL2 (PubMed:29272704). Interacts with AKIRIN2 (PubMed:25107474).|||Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5-16.5 dpc.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (By similarity). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (PubMed:17640523). Has a strong influence on vitamin D-mediated transcriptional activity from an enhancer vitamin D receptor element (VDRE). May be a link between mammalian SWI-SNF-like chromatin remodeling complexes and the vitamin D receptor (VDR) heterodimer. Mediates critical interactions between nuclear receptors and the BRG1/SMARCA4 chromatin-remodeling complex for transactivation (By similarity).|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Cavin3 ^@ http://purl.uniprot.org/uniprot/Q91VJ2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAVIN family.|||Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4 (PubMed:19546242). Interacts with PRKCD and with phosphatidylserine. Phosphatidylserine may form a bridge between PKC and PKC-binding partners and stabilize the binding (PubMed:9054438). Interacts with PER2 (PubMed:23079727). Interacts with CAVIN1 (PubMed:19546242, PubMed:25588833). Interacts (via leucine-zipper domain) with CAV1 in a cholesterol-sensitive manner (PubMed:25588833). Interacts with EPS15L1 (By similarity).|||Cytoplasm|||In vitro, phosphorylated by PRKCD.|||Lung, heart, skeletal muscle, liver, brain, vascular and urinary bladder smooth muscle (at protein level). Strongly expressed in uterus, ovary, mammary and epithelial cells. Also expressed in spleen, intestine, kidney and testis.|||Mice show reduced density of membrane caveolae in the arterial smooth muscle and the urinary bladder but show no loss of endothelial caveolae in lung and heart.|||Regulates the traffic and/or budding of caveolae (By similarity). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in smooth muscle but not in the lung and heart endothelial cells (PubMed:28285351, PubMed:23652019). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by promoting the rapid release of caveolae from the cell surface (PubMed:25588833). Plays a role in the regulation of the circadian clock. Modulates the period length and phase of circadian gene expression and also regulates expression and interaction of the core clock components PER1/2 and CRY1/2 (PubMed:23079727).|||The leucine-zipper domain is essential for its localization in the caveolae and for its interaction with CAV1 and EPS15L1.|||Up-regulated in serum-starvated cells or during cell growth arrest.|||caveola|||cytosol http://togogenome.org/gene/10090:Lipe ^@ http://purl.uniprot.org/uniprot/P54310 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 'GDXG' lipolytic enzyme family.|||Cell membrane|||Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (PubMed:15550674, PubMed:20625037, PubMed:21454566, PubMed:23066022, PubMed:23291629). Shows a preferential hydrolysis of DAGs over TAGs and MAGs and of the fatty acid (FA) esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity). Preferentially hydrolyzes FA esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:23066022). Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (PubMed:20625037, PubMed:21454566). In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production (By similarity).|||Lipid droplet|||Monomer and homodimer (By similarity). Interacts with CAVIN1 in the adipocyte cytoplasm (By similarity). Interacts with PLIN5 (PubMed:19717842).|||Phosphorylation by AMPK reduces its translocation towards the lipid droplets.|||Total acylglycerol levels are unaltered whereas diacylglycerol concentrations are drastically increased in white adipose tissue of knockout mice when compared to wild-type littermates.|||caveola|||cytosol http://togogenome.org/gene/10090:Rbfox2 ^@ http://purl.uniprot.org/uniprot/A0A2K6EDK7|||http://purl.uniprot.org/uniprot/Q8BP71 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in brain neurons (at protein level). Detected in heart, brain, embryo, lung, liver, kidney and ovary.|||Interacts with ER-alpha N-terminal activation domain.|||Nucleus|||RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Prevents binding of U2AF2 to the 3'-splice site. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis. Seems to act as a coregulatory factor of ER-alpha (By similarity).|||RNA-binding protein that regulates alternative splicing events.|||Up-regulated by androgens in cultured motor neuron cells. http://togogenome.org/gene/10090:Scfd1 ^@ http://purl.uniprot.org/uniprot/Q8BRF7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Golgi stack membrane|||Interacts with STX17. Interacts with STX5A. Interacts with the COG complex via COG4 (By similarity).|||Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. Involved in vesicular transport between the endoplasmic reticulum and the Golgi (By similarity). http://togogenome.org/gene/10090:Chga ^@ http://purl.uniprot.org/uniprot/P26339 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chromogranin/secretogranin protein family.|||Binds calcium with a low-affinity.|||Inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist. Can induce mast cell migration, degranulation and production of cytokines and chemokines.|||O-glycosylated; contains chondroitin sulfate (CS). CS attachment is pH-dependent, being observed at mildly acidic conditions of pH 5 but not at neutral pH, and promotes self-assembly in vitro.|||Regulates granule biogenesis in endocrine cells by up-regulating the transcription of protease nexin 1 (SERPINE2) via a cAMP-PKA-SP1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation (PubMed:21436258). Pyroglutaminated (pGlu)-serpinin exerts an antiapoptotic effect on cells exposed to oxidative stress (PubMed:21537909).|||Secreted|||Self-interacts; self-assembly is promoted in vitro by chondroitin sulfate attachment which occurs at mildly acidic pH conditions (By similarity). Interacts with SCG3; this interaction is optimal in conditions mimicking the lumenal milieu of the trans-Golgi network, i.e. pH 5.5 and 10 mM Ca(+2) (PubMed:12388744).|||Strongly inhibits glucose induced insulin release from the pancreas.|||neuronal dense core vesicle|||secretory vesicle http://togogenome.org/gene/10090:Cox6b2 ^@ http://purl.uniprot.org/uniprot/Q059Q8|||http://purl.uniprot.org/uniprot/Q80ZN9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytochrome c oxidase subunit 6B family.|||Belongs to the cytochrome c oxidase subunit 6B.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane|||Testis specific. http://togogenome.org/gene/10090:Rpusd3 ^@ http://purl.uniprot.org/uniprot/Q14AI6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pseudouridine synthase RluA family.|||Catalyzes uridine to pseudouridine isomerization (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs), a post-transcriptional modification necessary for their translation. Acts at position 390 in COXI mt-mRNA and at position 697-699 in mitochondrial COXIII mt-mRNA. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and may play a role in mitochondrial ribosome biogenesis.|||Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA.|||Mitochondrion matrix http://togogenome.org/gene/10090:Mettl21e ^@ http://purl.uniprot.org/uniprot/Q8CDZ2 ^@ Function|||Similarity ^@ Belongs to the methyltransferase superfamily. METTL21 family.|||Protein-lysine methyltransferase. http://togogenome.org/gene/10090:Cd3e ^@ http://purl.uniprot.org/uniprot/A6H6M1|||http://purl.uniprot.org/uniprot/P22646 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Absence of CD3E leads to the complete absence of mature T-cells. Thymocyte development is arrested at the early double-negative (DN) stage.|||Cell membrane|||Membrane|||Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development (PubMed:19956738, PubMed:24899501). Participates also in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region.|||Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.|||The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with CD6. Interacts with NCK1 (PubMed:24470497). http://togogenome.org/gene/10090:Zmpste24 ^@ http://purl.uniprot.org/uniprot/B9EHY2|||http://purl.uniprot.org/uniprot/Q80W54 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M48A family.|||Binds 1 zinc ion per subunit.|||Early endosome membrane|||Endoplasmic reticulum membrane|||Inhibited by HIV protease inhibitors, such as lopinavir, tipranavir and nelfinavir, leading to defects in lamin A/LMNA maturation and accumulation of prelamin-A/C precursors in cells (PubMed:17652517, PubMed:27462105). This causes defects in nuclear envelope integrity and release of DNA in the cytosol, activating the AIM2 inflammasome (PubMed:27462105).|||Late endosome membrane|||Nucleus inner membrane|||Proteolytically removes the C-terminal three residues of farnesylated proteins.|||Severe growth retardation and premature death (PubMed:11923874). Mice gain weight slowly, appear malnourished and exhibit progressive hair loss (PubMed:12235369). Mice suffer from dilated cardiomyopathy, muscular dystrophy and lipodystrophy due to defects in lamin A/LMNA maturation (PubMed:11923874). Mice also show spontaneous bone fractures and muscle weakness due to defects in lamin A/LMNA maturation (PubMed:12235369). Mutant mice show increased viral protein expression, enhanced viral reporter activity, and higher titers of infectious viral particles (PubMed:28246125).|||The metalloprotease domain is constituted by the two C-terminal nuclear regions.|||Transmembrane metalloprotease whose catalytic activity is critical for processing lamin A/LMNA on the inner nuclear membrane and clearing clogged translocons on the endoplasmic reticulum (PubMed:11923874, PubMed:12235369, PubMed:17652517, PubMed:27462105). Proteolytically removes the C-terminal three residues of farnesylated proteins (PubMed:11399759, PubMed:17652517). Plays also an antiviral role independently of its protease activity by restricting enveloped RNA and DNA viruses (PubMed:28246125). Mechanistically, controls IFITM antiviral pathway to hinder viruses from breaching the endosomal barrier by modulating membrane fluidity (PubMed:28246125). http://togogenome.org/gene/10090:Tcp10c ^@ http://purl.uniprot.org/uniprot/E9Q046|||http://purl.uniprot.org/uniprot/Q8C641 ^@ Similarity ^@ Belongs to the TCP10 family. http://togogenome.org/gene/10090:Mup14 ^@ http://purl.uniprot.org/uniprot/A2CEK7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Galnt17 ^@ http://purl.uniprot.org/uniprot/Q59J92|||http://purl.uniprot.org/uniprot/Q7TT15 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Golgi apparatus membrane|||May catalyze the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.|||Membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Samd11 ^@ http://purl.uniprot.org/uniprot/Q1RNF8 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed from 18 dpc in the outer aspect of neuroblastic layer (NBL).|||Homodimer.|||May play a role in photoreceptor development.|||Nucleus|||Predominantly expressed in retinal photoreceptors and pineal gland. http://togogenome.org/gene/10090:Or8g53 ^@ http://purl.uniprot.org/uniprot/Q8VFN4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdh8 ^@ http://purl.uniprot.org/uniprot/Q7TSK3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Calcium-dependent cell-adhesion protein (By similarity). May play a role in activity-induced synaptic reorganization underlying long term memory (By similarity). Could be involved in CDH2 internalization through TAOK2/p38 MAPK pathway (By similarity). In hippocampal neurons, may play a role in the down-regulation of dendritic spines, maybe through its action on CDH2 endocytosis.|||Cell membrane|||Due to intron retention.|||Postsynaptic cell membrane|||Presynaptic cell membrane|||The N-terminal extracellular domain forms homophilic interactions; these interactions activate p38 MAPK via TAOK2 and trigger endocytosis. Interacts with CDH2; this interaction may lead to CDH2 cointernalization. Interacts with CDH11. Interacts with TAOK2.|||dendrite http://togogenome.org/gene/10090:Ankmy2 ^@ http://purl.uniprot.org/uniprot/Q3TPE9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with the retinal-specific guanylyl cyclase GC1.|||May be involved in the trafficking of signaling proteins to the cilia.|||cilium http://togogenome.org/gene/10090:Cpne4 ^@ http://purl.uniprot.org/uniprot/Q8BLR2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the copine family.|||Interacts (via VWFA domain) with ACTB, BCOR, BICD2, CCDC22, CDC42BPB, CEP162, MYCBP2, NONO, PDCD6, PITPNM2, RDX, SKIL, SKT, SPTBN1, UBE2O and WTAP.|||Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes. http://togogenome.org/gene/10090:Dus2 ^@ http://purl.uniprot.org/uniprot/Q9D7B1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Dus family. Dus2 subfamily.|||Cytoplasm|||Dihydrouridine synthase. Catalyzes the NADPH-dependent synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. Negatively regulates the activation of EIF2AK2/PKR.|||Efficient dihydrouridine synthesis requires the presence of both the catalytic domain and the C-terminal RNA-binding DRBM domain.|||Endoplasmic reticulum|||Interacts with EPRS1. Interacts (via DRBM domain) with PRKRA and EIF2AK2/PKR (via DRBM 1 domain). http://togogenome.org/gene/10090:Or11h23 ^@ http://purl.uniprot.org/uniprot/E9Q9Z0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Csn1s2b ^@ http://purl.uniprot.org/uniprot/A0A0G2JDP4|||http://purl.uniprot.org/uniprot/P02664|||http://purl.uniprot.org/uniprot/Q3TP31 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-casein family.|||Important role in the capacity of milk to transport calcium phosphate.|||Mammary gland specific. Secreted in milk.|||Secreted http://togogenome.org/gene/10090:Gm20843 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Iigp1 ^@ http://purl.uniprot.org/uniprot/J7NNX8|||http://purl.uniprot.org/uniprot/Q9QZ85 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.|||Cytoplasm|||Endoplasmic reticulum membrane|||GTPase with low activity. Has higher affinity for GDP than for GTP. Plays a role in resistance to intracellular pathogens. Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite. Mediates resistance to C.trachomatis infection by targeting bacterial inclusions to autophagosomes for subsequent lysosomal destruction.|||Golgi stack membrane|||Monomer, as apoenzyme and in the GDP-bound form. Homooligomer, upon GTP binding. Interacts with HOOK3.|||Nucleus membrane|||Parasitophorous vacuole membrane|||Up-regulated by IFNG, IFNA1 and lipopolysaccharide (LPS) within 20 hours. Transiently up-regulated during the early stages of infection by Listeria monocytogenes. After 6 days expression is back to basal levels. http://togogenome.org/gene/10090:Or4q3 ^@ http://purl.uniprot.org/uniprot/Q7TRM4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Serpina1e ^@ http://purl.uniprot.org/uniprot/Q00898 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Does not inhibit elastase or chymotrypsin. No target protease has been identified to date.|||Murine alpha-1-antitrypsin is represented by a cluster of up to 6 individual Serpina1-related genes. The precise complement of Serpina1-related genes present varies according to the strain of the animal.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the active site of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity. http://togogenome.org/gene/10090:Ms4a4b ^@ http://purl.uniprot.org/uniprot/Q9ES61 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Trub1 ^@ http://purl.uniprot.org/uniprot/Q8C0D0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pseudouridine synthase TruB family.|||Nucleus|||Pseudouridine synthase that catalyzes pseudouridylation of mRNAs and tRNAs. Mediates pseudouridylation of mRNAs with the consensus sequence 5'-GUUCNANNC-3', harboring a stem-loop structure. Constitutes the major pseudouridine synthase acting on mRNAs. Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs. Promotes the processing of pri-let-7 microRNAs (pri-miRNAs) independently of its RNA pseudouridylate synthase activity. Acts by binding to the stem-loop structure on pri-let-7, preventing LIN28-binding (LIN28A and/or LIN28B), thereby enhancing the interaction between pri-let-7 and the microprocessor DGCR8, which mediates miRNA maturation.|||cytosol http://togogenome.org/gene/10090:Mysm1 ^@ http://purl.uniprot.org/uniprot/Q69Z66 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M67A family. MYSM1 subfamily.|||Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5. Binds histones (By similarity).|||Contains an N-terminal SANT domain that mediates histone/DNA binding, a central SWIRM domain to mediate interaction with chromatin associated proteins, and a C-terminal MPN domain that contains the metalloprotease activity.|||Cytoplasm|||Deficient mice elicit hyper-inflammatory responses, are more susceptible to septic shock, more resistant to RNA virus replication but exhibit early death upon DNA viral infection (PubMed:26474655, PubMed:33086059). They also show an impaired B-cell development (PubMed:22169041, PubMed:26348977, PubMed:27895164). In a similar way, NK-cell and dendritic cell development is impaired in deletion mutant (PubMed:25217698, PubMed:24062447). An enhanced systemic inflammation can be observed characterized by higher cytokine levels, as well as the hepatocellular enzyme alanine aminotransferase, a marker of liver damage (PubMed:30405132).|||Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response (PubMed:26474655, PubMed:27895164, PubMed:30405132). Participates in the normal programming of B-cell responses to antigen after the maturation process (PubMed:27895164). Within the cytoplasm, plays critical roles in the repression of innate immunity and autoimmunity (PubMed:26474655, PubMed:30405132). Removes 'Lys-63'-linked polyubiquitins from TRAF3 and TRAF6 complexes (PubMed:26474655). Attenuates NOD2-mediated inflammation and tissue injury by promoting 'Lys-63'-linked deubiquitination of RIPK2 component (PubMed:30405132). Suppresses the CGAS-STING1 signaling pathway by cleaving STING1 'Lys-63'-linked ubiquitin chains (PubMed:33086059). In the nucleus, acts as a hematopoietic transcription regulator derepressing a range of genes essential for normal stem cell differentiation including EBF1 and PAX5 in B-cells, ID2 in NK-cell progenitor or FLT3 in dendritic cell precursors (PubMed:22169041, PubMed:24062447, PubMed:25217698, PubMed:26348977). Deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, leading to dissociation of histone H1 from the nucleosome (By similarity).|||Nucleus http://togogenome.org/gene/10090:Unc5c ^@ http://purl.uniprot.org/uniprot/O08747|||http://purl.uniprot.org/uniprot/Q3UQ08|||http://purl.uniprot.org/uniprot/Q3URW2 ^@ Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the unc-5 family.|||Cell membrane|||Cell surface|||Defects in Unc5c are the cause of rostral cerebellar malformation (Rcm). Rcm is characterized by cerebellar and midbrain defects, apparently as a result of abnormal neuronal migration.|||Detected at 15 dpc in the cortex and cerebellum and at postnatal day 2 and 4 in the cerebellum (at protein level).|||Expressed in cortical and cerebellar neurons, including cells of the external and internal granular layer and of the Purkinje cell layer (at protein level) (PubMed:22685302, PubMed:28483977). Mainly expressed in regions of differentiating neurons (PubMed:9126743). Highly expressed in brain and lung (PubMed:9126743, PubMed:9389662). Expressed in the cerebellum and the neurons of the hippocampus, with enrichment in neurons of the CA3 hippocampal pyramidal layer (PubMed:25419706). Weakly expressed in testis, ovary, spleen, thymus and bladder (PubMed:9126743). Expressed at very low level in kidney, intestine and salivary gland (PubMed:9126743).|||Interacts with DCC (via cytoplasmic domain) (PubMed:10399920, PubMed:11533026). Interacts (tyrosine phosphorylated form) with PTPN11 (PubMed:11533026). Interacts (via extracellular domain) with FLRT3 (via extracellular domain) (PubMed:22405201). Interacts (via Ig-like C2-type domain) with DSCAM (via extracellular domain) (PubMed:22685302). Interacts (via death domain) with DAPK1 (By similarity). Interacts (via cytoplasmic domain) with TUBB3; this interaction is decreased by NTN1/Netrin-1 (PubMed:28483977).|||Membrane|||Phosphorylated on different cytoplasmic tyrosine residues (PubMed:11533026). Phosphorylation of Tyr-568 leads to an interaction with PTPN11 phosphatase, suggesting that its activity is regulated by phosphorylation/dephosphorylation (PubMed:11533026). Tyrosine phosphorylation is netrin-dependent (PubMed:11533026, PubMed:22685302).|||Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.|||Receptor for netrin required for axon guidance (PubMed:22685302, PubMed:10399920). Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (PubMed:10399920, PubMed:22685302). NTN1/Netrin-1 binding might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Axon repulsion in growth cones may also be caused by its association with DCC that may trigger signaling for repulsion (PubMed:10399920). Might also collaborate with DSCAM in NTN1-mediated axon repulsion independently of DCC (PubMed:22685302). Also involved in corticospinal tract axon guidance independently of DCC (PubMed:9126743, PubMed:9389662, PubMed:12451134). Involved in dorsal root ganglion axon projection towards the spinal cord (By similarity). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity).|||Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding.|||axon|||dendrite|||filopodium|||growth cone|||lamellipodium|||synaptosome http://togogenome.org/gene/10090:Cyp2c38 ^@ http://purl.uniprot.org/uniprot/P56655 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that primarily catalyzes the epoxidation of 11,12 double bond of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) forming 11,12-epoxyeicosatrienoic acid (11,12-EET) regioisomer. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Liver, brain, kidney, and intestine, with trace amounts in lung and heart.|||Microsome membrane http://togogenome.org/gene/10090:Arl1 ^@ http://purl.uniprot.org/uniprot/P61211|||http://purl.uniprot.org/uniprot/Q14AC7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||GTP-binding protein. Can activate phospholipase D with very low efficiency. Important for normal function of the Golgi apparatus (By similarity).|||Golgi apparatus membrane|||Membrane|||The GTP-bound form interacts with GOLGA1, GOLGA4 and RGPD8. The GTP-bound form directly interacts with ARFIP2; this interaction leads to an increase in the amount of bound GTP at steady state level. Binds to SCOC, preferentially in its GTP-bound form. May interact with UNC119 (By similarity). http://togogenome.org/gene/10090:Ptbp1 ^@ http://purl.uniprot.org/uniprot/P17225 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in myoblast; expression gradually decreases during muscle cell differentiation (at protein level).|||Monomer. Part of a ternary complex containing KHSRP, PTBP1, PTBP2 and HNRPH1. Interacts with SFPQ (By similarity). Interacts with RAVER1.|||Nucleus|||Plays a role in pre-mRNA splicing and in the regulation of alternative splicing events. Activates exon skipping of its own pre-mRNA during muscle cell differentiation. Binds to the polypyrimidine tract of introns. May promote RNA looping when bound to two separate polypyrimidine tracts in the same pre-mRNA. May promote the binding of U2 snRNP to pre-mRNA. Cooperates with RAVER1 to modulate switching between mutually exclusive exons during maturation of the TPM1 pre-mRNA. Represses the splicing of MAPT/Tau exon 10. Binds to polypyrimidine-rich controlling element (PCE) of CFTR and promotes exon skipping of CFTR exon 9, thereby antagonizing TIA1 and its role in exon inclusion of CFTR exon 9. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to a polypyrimidine tract flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform.|||The C-terminal 195 amino acids of PTB are sufficient for specific RNA binding. http://togogenome.org/gene/10090:Pola2 ^@ http://purl.uniprot.org/uniprot/P33611|||http://purl.uniprot.org/uniprot/Q8C2T6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis (By similarity). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity).|||Belongs to the DNA polymerase alpha subunit B family.|||Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (By similarity). Within the complex, POLA1 directly interacts with PRIM2 (By similarity).|||Nucleus|||Phosphorylated in a cell cycle-dependent manner, in G2/M phase. http://togogenome.org/gene/10090:St6galnac4 ^@ http://purl.uniprot.org/uniprot/Q8C3J2|||http://purl.uniprot.org/uniprot/Q9R2B6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Developmentally regulated.|||Golgi apparatus membrane|||High expression in brain and colon and to a lesser extent in lung, heart, kidney, spleen and thymus.|||Membrane|||Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of glycoproteins and glycolipids forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer of a sialyl group onto a GalNAc residue inside the backbone core chains (PubMed:10207017, PubMed:10601645). Prefers O-glycans to glycoproteins or glycolipids (PubMed:10207017). http://togogenome.org/gene/10090:Nans ^@ http://purl.uniprot.org/uniprot/Q99J77 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Produces N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) from N-acetylmannosamine 6-phosphate. Has no detectable activity towards N-acetylmannosamine or mannose 6-phosphate.|||Ubiquitous. http://togogenome.org/gene/10090:Hoga1 ^@ http://purl.uniprot.org/uniprot/Q9DCU9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DapA family.|||Catalyzes the final step in the metabolic pathway of hydroxyproline.|||Homotetramer.|||Inhibited by divalent cations.|||Mitochondrion http://togogenome.org/gene/10090:Btnl10 ^@ http://purl.uniprot.org/uniprot/Q9JK39 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Membrane http://togogenome.org/gene/10090:Paqr9 ^@ http://purl.uniprot.org/uniprot/Q6TCG2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ADIPOR family.|||Cell membrane|||Homodimer.|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(s) mediated pathway. May be involved in regulating rapid P4 signaling in the nervous system. Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone. http://togogenome.org/gene/10090:Ppp1r12b ^@ http://purl.uniprot.org/uniprot/A6H644 ^@ Subcellular Location Annotation|||Subunit ^@ PP1 comprises a catalytic subunit, and one or several targeting or regulatory subunits.|||stress fiber http://togogenome.org/gene/10090:Vamp8 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0R1|||http://purl.uniprot.org/uniprot/O70404 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptobrevin family.|||Cell membrane|||Early endosome membrane|||Expressed abundantly in the kidney, less in the liver, brain, kidney, heart, lung, pancreas and placenta.|||Forms a SNARE complex composed of VAMP8, SNAP29 and STX17 involved in fusion of autophagosome with lysosome (By similarity). Found in a number of SNARE complexes with NAPA, SNAP23, SNAP25, STX1A, STX4, STX7, STX8 and VTI1B (PubMed:15363411). Interacts with PICALM (PubMed:22118466). SNARE complex formation and binding by PICALM are mutually exclusive processes for VAMP8 (PubMed:22118466). Interacts with SBF2/MTMR13 (By similarity). Interacts with RAB21 (in GTP-bound form) in response to starvation; the interaction probably regulates VAMP8 endolysosomal trafficking (By similarity). Interacts with STX17; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with TRIM6 (By similarity).|||Late endosome membrane|||Lysosome membrane|||Membrane|||SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. VAMP8 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane via its interaction with the STX17-SNAP29 binary t-SNARE complex (By similarity). Also required for dense-granule secretion in platelets (By similarity). Also plays a role in regulated enzyme secretion in pancreatic acinar cells (PubMed:15363411). Involved in the abscission of the midbody during cell division, which leads to completely separate daughter cells (By similarity). Involved in the homotypic fusion of early and late endosomes (By similarity). Participates also in the activation of type I interferon antiviral response through a TRIM6-dependent mechanism (By similarity).|||Zymogen granule membrane http://togogenome.org/gene/10090:Gm21642 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Zdhhc17 ^@ http://purl.uniprot.org/uniprot/Q80TN5 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autopalmitoylated. Autopalmitoylation has a regulatory role in ZDHHC17-mediated Mg(2+) transport.|||Belongs to the DHHC palmitoyltransferase family. AKR/ZDHHC17 subfamily.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasmic vesicle membrane|||Expressed in liver, testis, kidney, heart, pancreas and brain. Highest expression was seen in the brain. Localized predominantly in the perinuclear regions of neurons from the cortex, striatum and hippocampus. Colocalized with HTT in the medium spiny neurons of the striatum and the spiny neurons that project into the globus pallidus.|||Golgi apparatus membrane|||Highly expressed in neurons during their differentiation.|||Interacts (via ANK repeats) with numerous proteins (via the consensus sequence motif [VIAP]-[VIT]-x-x-Q-P) (By similarity). Interacts (via ANK repeats) with CLIP3 (PubMed:26198635). Interacts (via ANK repeats) with HTT (PubMed:26198635). Interacts (via ANK repeats) with DNAJC5 (via C-terminus) (PubMed:25253725, PubMed:26198635). Interacts (via ANK repeats) with MAP6 (PubMed:26198635). Interacts (via ANK repeats) with SNAP23 (PubMed:26198635). Interacts (via ANK repeats) with SNAP25 (PubMed:25253725, PubMed:26198635). Interacts (via ANK repeats) with EVL (By similarity). Interacts with SPRED1 and SPRED3 (PubMed:24705354). Interacts with GPM6A and OPTN (By similarity). May interact (via ANK repeats) with SPRED2 (PubMed:28882895). May interact with NTRK1; may regulate its localization and function (PubMed:26232532).|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (PubMed:15489887, PubMed:15603741, PubMed:25253725, PubMed:27911442). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (PubMed:28167757). Palmitoyltransferase specific for a subset of neuronal proteins, including SNAP25, DLG4/PSD95, GAD2, SYT1 and HTT (PubMed:15489887, PubMed:15603741, PubMed:25253725). Also palmitoylates neuronal protein GPM6A as well as SPRED1 and SPRED3 (By similarity). Could also play a role in axonogenesis through the regulation of NTRK1 and the downstream ERK1/ERK2 signaling cascade (PubMed:26232532). May be involved in the sorting or targeting of critical proteins involved in the initiating events of endocytosis at the plasma membrane (By similarity). May play a role in Mg(2+) transport (By similarity). Could also palmitoylate DNAJC5 and regulate its localization to the Golgi membrane (PubMed:18596047). Palmitoylates CASP6, thereby preventing its dimerization and subsequent activation (PubMed:27911442).|||Presynaptic cell membrane|||The DHHC domain is required for palmitoyltransferase activity.|||Up-regulated by low extracellular Mg(2+). http://togogenome.org/gene/10090:Abcb1a ^@ http://purl.uniprot.org/uniprot/P21447 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.|||Cell membrane|||Cytoplasm|||In mouse the MDR gene family includes three or more related but distinct cellular genes.|||Interacts with PSMB5.|||Translocase activity is inhibited by verapamil and is sensitive to energy depletion. C1orf115 regulates drug efflux through modulation of ABCB1 localization and activity.|||Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (By similarity). http://togogenome.org/gene/10090:Tdrp ^@ http://purl.uniprot.org/uniprot/Q8C5P7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TDRP family.|||Contributes to normal sperm motility, but not essential for male fertility.|||Cytoplasm|||Interacts with PRM2.|||Nucleus|||Strongly expressed in testis. Also detected at lower levels in epididymis, bone marrow and kidney.|||Viable with no gross morphological defects. Morphology of testis tissue and mature epididymal sperm is normal. Sperm counts are also normal. Sperm motility is reduced, however this has no significant effect on male fertility. http://togogenome.org/gene/10090:Fads2b ^@ http://purl.uniprot.org/uniprot/Q0VAX3 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the fatty acid desaturase type 1 family.|||Endoplasmic reticulum membrane|||The histidine box domains may contain the active site and/or be involved in metal ion binding. http://togogenome.org/gene/10090:Kctd1 ^@ http://purl.uniprot.org/uniprot/Q5M956 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Can form homodimers. Interacts with TFAP2A, TFAP2B and TFAP2C via the BTB domain (By similarity).|||May repress the transcriptional activity of AP-2 family members, including TFAP2A, TFAP2B and TFAP2C to various extent.|||Nucleus|||Sumoylated. http://togogenome.org/gene/10090:Plpp4 ^@ http://purl.uniprot.org/uniprot/Q0VBU9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Magnesium-independent phospholipid phosphatase with broad substrate specificity. Preferentially catalyzes the conversion of diacylglycerol pyrophosphate into phosphatidate but can also act on phosphatidate and lysophosphatidate. Phospholipid phosphatases are involved in both the synthesis of lipids and the degradation or generation of lipid-signaling molecules like diacylglycerol.|||Magnesium-independent phospholipid phosphatase. Inhibited by N-ethylmaleimide.|||Membrane http://togogenome.org/gene/10090:Ciao3 ^@ http://purl.uniprot.org/uniprot/Q7TMW6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the NARF family.|||Component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. Seems to negatively regulate the level of HIF1A expression, although this effect could be indirect (By similarity).|||External component of the CIA complex. In the CIA complex, interacts directly with CIAO1 and MMS19. http://togogenome.org/gene/10090:Rprm ^@ http://purl.uniprot.org/uniprot/Q9JJ72 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ 'Reprimo' signifies stop/repress.|||Belongs to the reprimo family.|||By p53/TP53, following X-ray irradiation.|||Cytoplasm|||May be involved in the regulation of p53-dependent G2 arrest of the cell cycle. Seems to induce cell cycle arrest by inhibiting CDK1 activity and nuclear translocation of the CDC2 cyclin B1 complex.|||Membrane http://togogenome.org/gene/10090:Marveld3 ^@ http://purl.uniprot.org/uniprot/G3X8Q2|||http://purl.uniprot.org/uniprot/G3X9A4|||http://purl.uniprot.org/uniprot/Q9D956 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ As a component of tight junctions, plays a role in paracellular ion conductivity.|||Membrane|||Widely expressed with highest levels in small intestine, colon, stomach and lung. Liver expresses only isoform 2.|||tight junction http://togogenome.org/gene/10090:Lrrc69 ^@ http://purl.uniprot.org/uniprot/Q9D9Q0 ^@ Similarity ^@ Belongs to the LRRC69 family. http://togogenome.org/gene/10090:Vmn1r245 ^@ http://purl.uniprot.org/uniprot/K9J7G9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Elovl7 ^@ http://purl.uniprot.org/uniprot/Q9D2Y9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ELO family. ELOVL7 subfamily.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme with higher activity toward C18 acyl-CoAs, especially C18:3(n-3) acyl-CoAs and C18:3(n-6)-CoAs. Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs, and weakly toward C20:0-CoA. Little or no activity toward C22:0-, C24:0-, or C26:0-CoAs. May participate in the production of saturated and polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.|||Endoplasmic reticulum membrane|||Homodimer.|||The C-terminal di-lysine motif may confer endoplasmic reticulum localization. http://togogenome.org/gene/10090:Abo ^@ http://purl.uniprot.org/uniprot/P38649 ^@ Cofactor|||Domain|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Golgi stack membrane|||Secreted|||Submaxillary glands (at protein level).|||The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis. http://togogenome.org/gene/10090:Asb10 ^@ http://purl.uniprot.org/uniprot/D3YU18|||http://purl.uniprot.org/uniprot/Q91ZT7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Cytoplasm|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||Nucleus|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Spaca4 ^@ http://purl.uniprot.org/uniprot/Q80ZQ0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SPACA4/bouncer family.|||Cell membrane|||Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization.|||acrosome http://togogenome.org/gene/10090:Hapln3 ^@ http://purl.uniprot.org/uniprot/Q80WM5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HAPLN family.|||May function in hyaluronic acid binding.|||extracellular matrix http://togogenome.org/gene/10090:Psph ^@ http://purl.uniprot.org/uniprot/Q99LS3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAD-like hydrolase superfamily. SerB family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the last irreversible step in the biosynthesis of L-serine from carbohydrates, the dephosphorylation of O-phospho-L-serine to L-serine. L-serine can then be used in protein synthesis, to produce other amino acids, in nucleotide metabolism or in glutathione synthesis, or can be racemized to D-serine, a neuromodulator. May also act on O-phospho-D-serine.|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Insl5 ^@ http://purl.uniprot.org/uniprot/A2AIY3|||http://purl.uniprot.org/uniprot/Q9WUG6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the insulin family.|||Heterodimer of a B chain and an A chain linked by two disulfide bonds.|||Highest expression in colon with lower levels in thymus. Minimal levels in testis.|||May have a role in gut contractility or in thymic development and regulation. Activates RXFP4 with high potency and appears to be the endogenous ligand for this receptor (By similarity).|||Secreted http://togogenome.org/gene/10090:Rttn ^@ http://purl.uniprot.org/uniprot/Q8R4Y8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the rotatin family.|||Death at 11.5 dpc due to major developmental defects, including notochord degeneration, imperfect differentiation of somites and neural tube, axial rotation failure and randomized heart looping.|||Expressed at 7.5 dpc. At 8.5 dpc, expressed in telencephalon and somites. At 9.5 dpc, expressed in somites, forelimb bud, basal forebrain and first branchial arch. At 11.5 dpc, expressed in heart primordium and branchial arches.|||Interacts with PPP1R35; this interaction allows the mutual recruitment to the centriole.|||Involved in the genetic cascade that governs left-right specification. Required for correct asymmetric expression of NODAL, LEFTY and PITX2 (By similarity).|||cilium basal body http://togogenome.org/gene/10090:Btg1b ^@ http://purl.uniprot.org/uniprot/Q3V0S2 ^@ Similarity ^@ Belongs to the BTG family. http://togogenome.org/gene/10090:Sardh ^@ http://purl.uniprot.org/uniprot/Q3TWI2|||http://purl.uniprot.org/uniprot/Q99LB7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GcvT family.|||Binds 1 FAD covalently per monomer.|||Catalyzes the last step of the oxidative degradation of choline to glycine. Converts sarcosine into glycine.|||Mitochondrion matrix http://togogenome.org/gene/10090:Il11ra1 ^@ http://purl.uniprot.org/uniprot/Q3UIV4|||http://purl.uniprot.org/uniprot/Q64385 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A short soluble form is also released from the membrane by proteolysis (PubMed:26876177). The sIL11RA is formed either by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding, or directly secreted from the cells after alternative mRNA splicing (PubMed:26876177). mIL11RA is cleaved by the proteases ADAM10, ELANE and PRTN3 (PubMed:26876177).|||Belongs to the type I cytokine receptor family. Type 3 subfamily.|||First detected at low levels at 10.5 dpc in cranofacial mesenchyme and in parts of the nervous system. At 12.5 dpc, high expression found in heart, diaphragm, bronchi and in the mesenchyme surrounding precartilage condensations. At later stages, expressed in dental papilla, dermis, hair follicles and in the perichondrium and in regions containing chondro and osteo progenitor cells.|||Membrane|||Mice have disturbed cranial growth and suture activity.|||On IL11 binding, forms a multimer complex with IL6ST/gp130.|||Receptor for interleukin-11. The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells. Essential for the normal development of craniofacial bones and teeth.|||Secreted|||Soluble form of IL11 receptor (sIL11RA) that acts as an agonist of IL11 activity. The IL11:sIL11RA complex binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL11RA in a process called IL11 trans-signaling.|||Widely expressed in all adult tissues and in embryos. Highest levels in kidney, skeletal muscle and embryo. http://togogenome.org/gene/10090:Wasf2 ^@ http://purl.uniprot.org/uniprot/Q8BH43 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the SCAR/WAVE family.|||Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2. Directly interacts with BRK1. Interacts with human cytomegalovirus protein UL135. Interacts with FNBP1L (via the SH3 domain).|||Binds and activates the Arp2/3 complex via the C-terminal domain. Interacts with actin via the WH2 domain (By similarity).|||Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity).|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Cpa3 ^@ http://purl.uniprot.org/uniprot/P15089|||http://purl.uniprot.org/uniprot/Q542E3 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||secretory vesicle http://togogenome.org/gene/10090:Vangl2 ^@ http://purl.uniprot.org/uniprot/Q91ZD4 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Vang family.|||Cell membrane|||Defects in Vangl2 are a cause of the loop-tail (Lp) mutant phenotype. Heterozygous Lp mice exhibit a characteristic looped tail, while homozygous embryos show a completely open neural tube in the hindbrain and spinal region, a condition similar to the severe craniorachischisis defect in humans. Homozygotes also have complex cardiovascular defects including double-outlet right ventricle, perimembranous ventricular defects, double-sided aortic arch and associated abnormalities in the aortic arch arteries. Homozygotes show cytoplasmic accumulation of Vangl2 instead of the normal membrane localization, and Rhoa expression, which is detected in the mesenchymal cushion cells adjacent to the outflow tract, is lost in homozygotes. Homozygous embryos typically die shortly before or at birth.|||Homodimer and heterodimer with Vangl1. Interacts through its C-terminal region with the N-terminal half of DVL1, DVL2 and DVL3. The PDZ domain of DVL1, DVL2 and DVL3 is required for the interaction. Variants Glu-255 and Asn-464 impair interaction with the DVL proteins. Also interacts with the PDZ domains of MAGI3, SCRIB/SCRB1 and FZD3 (PubMed:15195140). Interacts with PRICKLE3 (By similarity).|||In the embryo, strongly expressed in the neuroectoderm from the earliest stages of neural induction through the late stages of neural tube closure. Detected in the dorso-ventral axis of the neural tube, but not in the floor plate. Expression is low at day 7 dpc; it peaks at 11 dpc, and it remains strong at 15 dpc and 17 dpc. Also expressed in the cochlear epithelium at days 14.5 dpc and 16.5 dpc. Detected at low levels in the outflow tract myocardium from 9.5 dpc with levels increasing by 11.5 dpc.|||Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate. Plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea. Required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process. Required for cell surface localization of FZD3 and FZD6 in the inner ear (PubMed:16495441).|||Primarily expressed in the brain and epididymis. Not detected in the cochlea of Lp mice. http://togogenome.org/gene/10090:Or12j2 ^@ http://purl.uniprot.org/uniprot/Q7TRT9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhox2d ^@ http://purl.uniprot.org/uniprot/W4VSN9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Wsb2 ^@ http://purl.uniprot.org/uniprot/O54929 ^@ Domain|||Function ^@ May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Ddx5 ^@ http://purl.uniprot.org/uniprot/Q8BTS0 ^@ Similarity ^@ Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily. http://togogenome.org/gene/10090:Gm21171 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Ten1 ^@ http://purl.uniprot.org/uniprot/Q9D7K2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TEN1 family.|||Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha. The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (By similarity).|||Component of the CST complex, composed of TEN1, CTC1 and STN1; in the complex interacts directly with STN1.|||Nucleus|||telomere http://togogenome.org/gene/10090:Tmem30a ^@ http://purl.uniprot.org/uniprot/Q8VEK0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF). Can also mediate the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations.|||Apical cell membrane|||Belongs to the CDC50/LEM3 family.|||Cell membrane|||Component of various P4-ATPase flippase complexes which consists of a catalytic alpha subunit and an accessory beta subunit. Interacts with ATP8A1 to form a flippase complex; this complex forms an intermediate phosphoenzyme. The ATP8A2:TMEM30A flippase complex has been purified, and ATP8B1:TMEM30A and ATP8B2:TMEM30A flippase complexes have been shown to form intermediate phosphoenzymes in vitro (By similarity). Interacts with alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C (PubMed:23269685, PubMed:30018401, PubMed:29799007).|||Expressed in photoreceptor cells; detected in retina outer segment (at protein level). Detected in hepatocytes liver sinusoidal endothelial cells and kidney brush border of the proximal tubules (at protein level). Expressed in brain (at protein level).|||Golgi apparatus|||Membrane|||N-glycosylated. Contains high mannose-type oligosaccharides.|||The N-terminal domain seems to play a role in the reaction cycle of thr catalytic subunit such as ATP8A2.|||secretory vesicle membrane http://togogenome.org/gene/10090:Mpp1 ^@ http://purl.uniprot.org/uniprot/P70290|||http://purl.uniprot.org/uniprot/Q542P4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the erythrocytes (at protein level).|||Belongs to the MAGUK family.|||Cell membrane|||During development of the retina, expression is highest in the inner, neuroblastic layer, while at later stages it is also present in the photoreceptor cell layer. Detected in the eye from 14.5 dpc onwards. Highly expressed in the liver and primitive gut, and at lower levels in the umbilical vein, the ventricular layer of the CNS and upper/lower jaw region. At 14.5 dpc and 16.5 dpc, expression in the liver and stomach is maintained. In addition, expression is present in bone structures (e.g. zygomatic bone, lower jawbone), cranial nerve ganglia [e.g. trigeminal (V) ganglion] and cochlea. The expression in the eye is seen in the neuroblastic layer. At 16.5 dpc and 18.5 dpc, a slightly higher expression is seen in the neuroblastic layer. At 16.5 dpc, strong expression in the upper part of the gut is maintained and with the onset of ossification, expression is seen in all bone structures of the body. At P7 and P90, expression in the eye is seen in the ganglion cell layer, the inner nuclear layer (INL) and photoreceptor cell layer.|||Essential regulator of neutrophil polarity. Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity.|||Heterodimer with PALS1. Interacts with DLG5 and NF2. Interacts (via guanylate kinase-like domain) with WHRN (via third PDZ domain).|||Neutrophils form multiple transient pseudopods upon chemotactic stimulation, and do not migrate efficiently in vitro.|||Palmitoylated.|||stereocilium http://togogenome.org/gene/10090:Rbm47 ^@ http://purl.uniprot.org/uniprot/D3YXZ5|||http://purl.uniprot.org/uniprot/Q91WT8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM RBM47 family.|||Cytoplasm|||Homodimer. Interacts with A1CF (PubMed:24916387). Interacts with APOBEC1; form an mRNA editing complex (By similarity).|||Homozygous knockout mice die before birth.|||Nucleus|||Single-stranded RNA-binding protein that functions in a variety of RNA processes, including alternative splicing, RNA stabilization, and RNA editing. Functions as an enzyme-substrate adapter for the cytidine deaminase APOBEC1. With APOBEC1 forms an mRNA editing complex involved into cytidine to uridine editing of a variety of mRNA molecules (PubMed:24916387, PubMed:30844405, PubMed:30309881). Through the binding of their 3'UTR, also stabilizes a variety of mRNAs and regulates the expression of genes such as the interferon alpha/beta receptor and interleukin-10 (PubMed:29844590). Also involved in the alternative splicing of several genes including TJP1. Binds the pre-mRNA (U)GCAUG consensus sequences in downstream intronic regions of alternative exons, regulating their exclusion and inclusion into mRNAs (By similarity). Independently of its RNA-binding activity, could negatively regulate MAVS by promoting its lysosomal degradation (By similarity). http://togogenome.org/gene/10090:Paxbp1 ^@ http://purl.uniprot.org/uniprot/P58501 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein linking the transcription factors PAX3 and PAX7 to the histone methylation machinery and involved in myogenesis. Associates with a histone methyltransferase complex that specifically mediates dimethylation and trimethylation of 'Lys-4' of histone H3. Mediates the recruitment of that complex to the transcription factors PAX3 and PAX7 on chromatin to regulate the expression of genes involved in muscle progenitor cells proliferation including ID3 and CDC20.|||Belongs to the GCF family.|||Interacts with PAX3 and PAX7. Interacts with WDR5; associates with a histone methyltransferase (HMT) complex composed at least of RBBP5, ASH2L, SET1, SET2 and KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4 through direct interaction with WDR5.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Ubiquitously expressed in all tissues tested including skeletal muscle. Expressed in primary myoblasts. http://togogenome.org/gene/10090:Foxred2 ^@ http://purl.uniprot.org/uniprot/Q3USW5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FOXRED2 family.|||Endoplasmic reticulum lumen|||Interacts with SEL1L. May interact with OS9 and DNAJC10. Interacts with TXNDC16.|||N-glycosylated.|||Probable flavoprotein which may function in endoplasmic reticulum associated degradation (ERAD). May bind non-native proteins in the endoplasmic reticulum and target them to the ubiquitination machinery for subsequent degradation (By similarity). http://togogenome.org/gene/10090:Scml2 ^@ http://purl.uniprot.org/uniprot/B1AVB4|||http://purl.uniprot.org/uniprot/B1AVB5|||http://purl.uniprot.org/uniprot/Q8BYC8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Fbxo28 ^@ http://purl.uniprot.org/uniprot/Q8BIG4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of a SCF (SKP1-cullin-F-box) protein ligase complex.|||Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation.|||kinetochore http://togogenome.org/gene/10090:Sec61b ^@ http://purl.uniprot.org/uniprot/Q9CQS8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC61-beta family.|||Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER) (By similarity). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides (By similarity). The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex (By similarity). The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER (By similarity). Required for PKD1/Polycystin-1 biogenesis (PubMed:28375157).|||Endoplasmic reticulum membrane|||The SEC61 channel-forming translocon complex consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63 (By similarity). The SEC61 channel associates with the multi-pass translocon (MPT) complex. Interacts with TRAM1 (By similarity). http://togogenome.org/gene/10090:Pgk2 ^@ http://purl.uniprot.org/uniprot/P09041 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphoglycerate kinase family.|||Cytoplasm|||Essential for sperm motility and male fertility but is not required for the completion of spermatogenesis (PubMed:19759366).|||Mice display greatly reduced ATP levels in sperm, severely impaired sperm motility and are infertile. No alteration in testis histology, sperm counts, or sperm ultrastructure seen.|||Monomer.|||Testis and sperm. Localized on the principle piece in the sperm (at protein level). Testis-specific. http://togogenome.org/gene/10090:Senp3 ^@ http://purl.uniprot.org/uniprot/Q9EP97 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C48 family.|||Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity). Interacts with EP300, NPM1 and CDCA8 (By similarity). Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148 (PubMed:22872859). Interacts with NOL9 (PubMed:22872859). Interacts with CCAR2 (By similarity).|||Cytoplasm|||On oxidative stress, SENP3 degradation is blocked by inhibition of its ubiquitination, which stabilizes it as it accumulates in the nucleoplasm.|||Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:11029585). Deconjugates SUMO2 from MEF2D, which increases its transcriptional activation capability (By similarity). Deconjugates SUMO2 and SUMO3 from CDCA8 (By similarity). Redox sensor that, when redistributed into nucleoplasm, can act as an effector to enhance HIF1A transcriptional activity by desumoylating EP300 (By similarity). Required for rRNA processing through deconjugation of SUMO2 and SUMO3 from nucleophosmin, NPM1 (By similarity). Plays a role in the regulation of sumoylation status of ZNF148 (By similarity). Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Deconjugates SUMO2 from KAT5 (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Ddhd1 ^@ http://purl.uniprot.org/uniprot/Q80YA3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PA-PLA1 family.|||Cytoplasm|||Forms homooligomers and, to a much smaller extent, heterooligomers with DDHD2. Interacts with SEC23A and SEC24C.|||Knockout mice have defects in the organization of mitochondria during spermiogenesis, leading to sperm malformation and male subfertility (PubMed:24599962). Genetic loss of DDHD1 leads to substantial reductions in polyunsaturated lysophospholipids in the brain, and reduced mechanical, but not thermal nociception (PubMed:30221923).|||Phospholipase A1 (PLA1) that hydrolyzes ester bonds at the sn-1 position of glycerophospholipids producing a free fatty acid and a lysophospholipid (PubMed:30221923) (Probable). Prefers phosphatidate (1,2-diacyl-sn-glycero-3-phosphate, PA) as substrate in vitro, but can efficiently hydrolyze phosphatidylinositol (1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol), PI), as well as a range of other glycerophospholipid substrates such as phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE), phosphatidylserine (1,2-diacyl-sn-glycero-3-phospho-L-serine, PS) and phosphatidylglycerol (1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol), PG) (PubMed:30221923) (Probable). Involved in the regulation of the endogenous content of polyunsaturated PI and PS lipids in the nervous system (PubMed:30221923). Changes in these lipids extend to downstream metabolic products like PI phosphates PIP and PIP2, which play fundamental roles in cell biology (PubMed:30221923). Regulates mitochondrial morphology (PubMed:24599962). These dynamic changes may be due to PA hydrolysis at the mitochondrial surface (PubMed:24599962). May play a regulatory role in spermatogenesis or sperm function (PubMed:24599962).|||Predominantly expressed in testis, in round and elongating spermatids, but not in spermatocytes (at protein level) (PubMed:24599962). Also expressed in the brain, and at lower levels in other tissues such as thymus and lung (at protein level) (PubMed:24599962). http://togogenome.org/gene/10090:Acadm ^@ http://purl.uniprot.org/uniprot/P45952 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated. Could occur at proximity of the cofactor-binding sites and reduce the catalytic activity. Could be deacetylated by SIRT3.|||Belongs to the acyl-CoA dehydrogenase family.|||Homotetramer. Interacts with the heterodimeric electron transfer flavoprotein ETF.|||Medium-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats (PubMed:16121256). The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (PubMed:16121256). Electron transfer flavoprotein (ETF) is the electron acceptor that transfers electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase) (By similarity). Among the different mitochondrial acyl-CoA dehydrogenases, medium-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 6 to 12 carbons long primary chains (PubMed:16121256).|||Mice lacking Mcad show increased neonatal mortality (PubMed:16121256). They display hypothermia and cold intolerance upon fasting (PubMed:16121256). Their serum and bile acylcarnitine profile is also different from wild-type mice, with an elevation of serum decenoylcarnitine compared to wild-type mice (PubMed:16121256). They also display hepatic steatosis following fast periods (PubMed:16121256). They develop significantly elevated concentrations of urinary adipic, suberic, and sebacic acids and hexanoylglycine (PubMed:16121256).|||Mitochondrion matrix http://togogenome.org/gene/10090:Nktr ^@ http://purl.uniprot.org/uniprot/P30415 ^@ Activity Regulation|||Function|||Subcellular Location Annotation ^@ Cell membrane|||Inhibited by cyclosporin A (CsA).|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Component of a putative tumor-recognition complex involved in the function of NK cells. http://togogenome.org/gene/10090:Eapp ^@ http://purl.uniprot.org/uniprot/Q5BU09 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with E2F1. The C-terminal half binds the N-terminal of E2F1. Also interacts with E2F2 and E2F3, but not E2F4.|||May play an important role in the fine-tuning of both major E2F1 activities, the regulation of the cell-cycle and the induction of apoptosis. Promotes S-phase entry, and inhibits p14(ARP) expression (By similarity).|||Nucleus http://togogenome.org/gene/10090:Itgal ^@ http://purl.uniprot.org/uniprot/B7ZN92|||http://purl.uniprot.org/uniprot/P24063|||http://purl.uniprot.org/uniprot/Q3TB85 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin alpha chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. The ITGAL alpha subunit associates with the ITGB2 beta subunit. Interacts with THBD.|||In resting T-cells, up to 40% of surface ITGAL is constitutively phosphorylated. Phosphorylation causes conformational changes needed for ligand binding and is necessary for the activation by some physiological agents.|||Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4 (PubMed:2051027). Integrin ITGAL/ITGB2 is a receptor for F11R (By similarity). Integrin ITGAL/ITGB2 is a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL (PubMed:29100055). Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes. Contributes to natural killer cell cytotoxicity. Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:16234355, PubMed:24158516). Required for generation of common lymphoid progenitor cells in bone marrow, indicating the role in lymphopoiesis (PubMed:25108025). Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages.|||Leukocytes.|||Membrane|||Mice show decreased cellularity in thymus but not spleen, and impaired early T cell development (PubMed:25108025). Obese mutant mice show decreased total number of T-cells, lower levels of neutrophil elastase and reduced cytotoxic T-cell proliferation in adipose tissue, as well as improved glucose tolerance and insulin resistance in comparison to obese wild type mice (PubMed:24158516). Splenocytes from mutant mice do not respond to extracellular Isg15 as demonstrated by lack of Ifng secretion in contrast to wild-type cells which secrete Ifng in response to treatment with Isg15 (PubMed:29100055).|||The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. The I-domain is necessary and sufficient for interaction with ICAM1 and F11R. http://togogenome.org/gene/10090:Atp6v1d ^@ http://purl.uniprot.org/uniprot/P57746|||http://purl.uniprot.org/uniprot/Q3U861 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase D subunit family.|||Membrane|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with SNX10 (By similarity).|||centrosome|||cilium|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Or13a17 ^@ http://purl.uniprot.org/uniprot/Q8VGM1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mafg ^@ http://purl.uniprot.org/uniprot/O54790 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated in erythroid cells by CREB-binding protein (CBP). Acetylation augments the DNA-binding activity of NFE2, but has no effect on binding NFE2.|||Belongs to the bZIP family. Maf subfamily.|||Expressed throughout the embryo up until 8.5 dpc with strong expression in the neural tube. Expression continues throughout the embryo with some intense expression also in the epithelium of the intestine, skeletal muscle, lens, retina, cranial nerve, and dorsal root ganglion cells. After birth, strong expression in the epidermis, hair follicles, epithelium of the digestive and respiratory tracts, and kidney tubules.|||Homodimer or heterodimer (By similarity). Homodimerization leads to transcriptional repression (By similarity). Forms high affinity heterodimers with members of the CNC-bZIP family such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3 (PubMed:31398338). Interacts with CREBBP; the interaction leads to acetylation of the basic region of MAFG and stimulation of NFE2 transcriptional activity through increased DNA binding (By similarity).|||Mice, although viable and fertile, exhibit abnormal megakaryocyte proliferation as well as age-dependent behavioral defects. Megakaryocytes display both anti-glycoprotein IIb immunoreactivity and anti-acetylcholinesterase activity.|||Nucleus|||Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (PubMed:16738329, PubMed:9679061). However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1 and NFE2L2, and recruiting them to specific DNA-binding sites (PubMed:16738329, PubMed:9679061). Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NFE2L2 transcription factor. Transcription factor, component of erythroid-specific transcription factor NFE2L2. Activates globin gene expression when associated with NFE2L2 (By similarity). May be involved in signal transduction of extracellular H(+) (By similarity).|||Sumoylation at Lys-14 is required for active transcriptional repression. http://togogenome.org/gene/10090:Slc23a3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J067|||http://purl.uniprot.org/uniprot/Q60850 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a sodium-dependent hypoxanthine transporter. May show xanthine-hypoxanthine exchange activity.|||Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.|||Cytoplasm|||Membrane http://togogenome.org/gene/10090:Teddm1a ^@ http://purl.uniprot.org/uniprot/E9QLK8|||http://purl.uniprot.org/uniprot/Q810U2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Membrane http://togogenome.org/gene/10090:Or8k22 ^@ http://purl.uniprot.org/uniprot/Q8VGS7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Exoc1 ^@ http://purl.uniprot.org/uniprot/Q5PPR2|||http://purl.uniprot.org/uniprot/Q6P1Y9|||http://purl.uniprot.org/uniprot/Q8R3S6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC3 family.|||Cell membrane|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Cytoplasm|||Midbody ring|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8. Interacts with EEF1A1. Interacts with SLC6A9; interaction increases the transporter capacity of SLC6A9 probably by promoting its insertion into the cell membrane.|||perinuclear region http://togogenome.org/gene/10090:Or51g2 ^@ http://purl.uniprot.org/uniprot/Q8VH11 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lyz1 ^@ http://purl.uniprot.org/uniprot/A0A077S9N1|||http://purl.uniprot.org/uniprot/P17897 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 22 family.|||Expressed strongly only in small intestine.|||Lysozyme C is capable of both hydrolysis and transglycosylation; it shows also a slight esterase activity. It acts rapidly on both peptide-substituted and unsubstituted peptidoglycan, and slowly on chitin oligosaccharides.|||Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Lyz1 is active against a range of Gram-positive and Gram-negative bacteria. Less effective than Lyz2 in killing Gram-negative bacteria. Lyz1 and Lyz2 are equally effective in killing Gram-positive bacteria.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Or4k45 ^@ http://purl.uniprot.org/uniprot/Q8VF48 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mccc1 ^@ http://purl.uniprot.org/uniprot/Q99MR8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylated.|||Biotin-attachment subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.|||Mitochondrion matrix|||Probably a dodecamer composed of six biotin-containing alpha subunits (MCCC1) and six beta (MCCC2) subunits (By similarity). Interacts (via the biotin carboxylation domain) with SIRT4 (PubMed:23438705). http://togogenome.org/gene/10090:Trim65 ^@ http://purl.uniprot.org/uniprot/Q8BFW4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:31310649, PubMed:34512673). Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs. This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (By similarity). Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade. Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (By similarity). Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649). In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673).|||Homo-multimerizes. Interacts with ARRDC4.|||TRIM65-deficient mice show impaired NLRP3 ubiquitination and enhanced NLRP3 inflammasome activation. http://togogenome.org/gene/10090:Or6c201 ^@ http://purl.uniprot.org/uniprot/Q8VGC2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gna12 ^@ http://purl.uniprot.org/uniprot/P27600 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(12) subfamily.|||Cell membrane|||Cytoplasm|||G proteins are composed of 3 units; alpha, beta and gamma (PubMed:16388592). The alpha chain contains the guanine nucleotide binding site (PubMed:16388592). Interacts with UBXD5 (By similarity). Interacts (in GTP-bound form) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane (By similarity). Interacts with RGS22 (By similarity). Interacts (via N-terminus) with NAPA; the interaction promotes CDH5 localization to plasma membrane (By similarity). Interacts with CTNND1 (via N-terminus); the interaction regulates CDH1-mediated cell-cell adhesion (PubMed:15240885). Interacts with PPP2R1A; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT (By similarity). Interacts (in GTP-bound form) with ARHGEF1 (PubMed:16388592). Interacts (in GTP-bound form) with ARHGEF11 (via RGS domain) (By similarity). Interacts (in GTP-bound form) with ARHGEF12 (via RGS domain) (PubMed:16388592).|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:19151758, PubMed:21212405, PubMed:22609986). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (By similarity). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (PubMed:19151758, PubMed:21212405). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (By similarity). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating pro-inflammatory cytokine production (By similarity). Inhibits CDH1-mediated cell adhesion in process independent from Rho activation (By similarity). Together with NAPA promotes CDH5 localization to plasma membrane (By similarity). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986).|||Lateral cell membrane|||Myristoylation of mutated N-terminus in place of original palmitoylation restores the transformation activity. http://togogenome.org/gene/10090:Tmem199 ^@ http://purl.uniprot.org/uniprot/B2RV69|||http://purl.uniprot.org/uniprot/Q5SYH2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump.|||Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. In aerobic conditions, required for intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. Necessary for endolysosomal acidification and lysosomal degradation (By similarity). May be involved in Golgi homeostasis (By similarity).|||COPI-coated vesicle membrane|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Membrane http://togogenome.org/gene/10090:Prl2c5 ^@ http://purl.uniprot.org/uniprot/Q9JLV9 ^@ Developmental Stage|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed in placenta (at protein level) (PubMed:10803597, PubMed:10537154, PubMed:16876275). Expressed in the tail hair follicle, with highest expression detected in the keratinocytes of the outer root sheath (PubMed:10803597). Expressed in ear skin with lesser amounts in small intestine (PubMed:10803597). Not detected in brain at 18 dpc, postnatal day 25 or postnatal day 55 (PubMed:16876275).|||In placenta, detected at 8 dpc, peaks at 12 dpc and declines thereafter.|||N-glycosylated and sialylated.|||Secreted http://togogenome.org/gene/10090:Dpep2 ^@ http://purl.uniprot.org/uniprot/Q8C255 ^@ Activity Regulation|||Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:12738806, does not hydrolyze cystinyl-bis-glycine but data is not shown in paper.|||Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.|||Dipeptidase that hydrolyzes leukotriene D4 (LTD4) into leukotriene E4 (LTE4) (PubMed:12738806). Hydrolyzes cystinyl-bis-glycine (By similarity).|||Expressed in heart, lung, testis, spleen and skeletal muscle. Not detected in kidney and brain.|||Homodimer; disulfide-linked.|||Independently of its dipeptidase activity can also modulate macrophage inflammatory response by acting as a regulator of NF-kappa-B inflammatory signaling pathway.|||Inhibited by L-penicillamine.|||Membrane|||Up-regulated during CVB3-induced viral myocarditis in the cardiac infiltrating macrophages. http://togogenome.org/gene/10090:Cstdc4 ^@ http://purl.uniprot.org/uniprot/B2RV77 ^@ Similarity ^@ Belongs to the cystatin family. http://togogenome.org/gene/10090:Rps24 ^@ http://purl.uniprot.org/uniprot/P62849|||http://purl.uniprot.org/uniprot/Q5M9M7|||http://purl.uniprot.org/uniprot/Q9D7P1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS24 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Required for processing of pre-rRNA and maturation of 40S ribosomal subunits (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Down-regulated during adipocyte differentiation and up-regulated during cellular transformation.|||nucleolus http://togogenome.org/gene/10090:Vps37c ^@ http://purl.uniprot.org/uniprot/Q8R105 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS37 family.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101, VPS28, MVB12A and MVB12B. Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and UBAP1 in a 1:1:1:1 stoichiometry. Interacts with HGS and STAM2. Interacts with CEP55 (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation (By similarity).|||Late endosome membrane|||Phosphorylated by TBK1. http://togogenome.org/gene/10090:Ccl9 ^@ http://purl.uniprot.org/uniprot/P51670|||http://purl.uniprot.org/uniprot/Q3U9T8 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||By interleukin-4; in the bone marrow macrophage.|||Expressed mainly in the liver, lung, and the thymus, although some expression has been detected in a wide variety of tissues except brain.|||Monokine with inflammatory, pyrogenic and chemokinetic properties. Circulates at high concentrations in the blood of healthy animals. Binding to a high-affinity receptor activates calcium release in neutrophils. It also inhibits colony formation of bone marrow myeloid immature progenitors.|||Secreted|||The N-terminal is proteolytically cleaved by proteases associated with inflammatory responses. The processed forms CCL9(29-101), CCL9(30-101) and CCL9(31-101) exhibit increase in CCR1-mediated signaling and chemotaxis assays in vitro. http://togogenome.org/gene/10090:Krtap15 ^@ http://purl.uniprot.org/uniprot/Q9QZU5 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PMG family.|||Expressed at high levels in skin and at lower levels in the developing mammary gland.|||In skin, expression starts shortly after birth and reaches a first maximum at 9 days. A second peak of expression is observed at 3.5 weeks, then levels decline and remain low in the adult. In the developing mammary gland, expression is detected exclusively at the onset of puberty.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Wdfy3 ^@ http://purl.uniprot.org/uniprot/Q6VNB8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in the developing central nervous system already at 11.5 dpc (PubMed:27648578). At 13.5 dpc, strong expression in the proliferative zones surrounding the lateral ventricle and weaker expression throughout the developing forebrain. At 14.5 dpc, highest expression within the proliferative regions surrounding the ventricles. Specifically expressed in the leptomeninges, cortical intermediate zone, choroid plexus and in radial glia cells within the ventricular zone (VZ). Within the VZ, expression is observed in a subset of cells actively undergoing mitosis. The expression persists through all phases of cell division, but decreases during telophase. Expression is often maintained in radial units, where it is the highest in progenitors closest to the ventricle, then gradually diminishes as distance from the ventricular surface increases (PubMed:15342963, PubMed:25198012). Expression levels in the brain decrease after birth (at protein level) (PubMed:15342963).|||Directly interacts with ATG5 and associates with the ATG12-ATG5-ATG16L complex. Interacts with p62/SQSTM1. Directly interacts with GABARAP, GABARAPL1 and GABARAPL2; the interaction with GABARAP is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies. Weakly interacts with MAP1LC3C; this interaction is direct. Does not interact with MAP1LC3A, nor MAP1LC3B (By similarity). Interacts with TRAF6 (PubMed:27330028).|||Homozygous mice are born at close to the expected Mendelian ratios, but die perinatally (PubMed:25198012, PubMed:27648578). Newborn animals exhibit striking abnormalities in the forebrain, midbrain and hindbrain, including visibly smaller brains and gross enlargement of the lateral ventricles. There is an apparent loss and disorganization of interhemispheric axonal tracts throughout the brain (PubMed:25198012, PubMed:27648578).|||Membrane|||Nucleus|||PML body|||Perikaryon|||Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3. Involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures) (By similarity). Important for normal brain development (PubMed:25198012, PubMed:27648578). Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (PubMed:27648578). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (By similarity). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (PubMed:27330028). After cytokinetic abscission, involved in midbody remnant degradation. In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (By similarity).|||The FYVE domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns3P).|||The LIR (LC3-interacting region) motif mediates the interaction with MAP1LC3C and other ATG8 family members.|||Widely expressed, with high levels in the brain (at protein level) (PubMed:15342963, PubMed:15292400, PubMed:27648578). In the brain, expressed by both neuronal and non-neuronal cells (PubMed:27648578). Expressed in bones, in the periosteum, cartilage, growth plate, trabeculae of the primary spongiosa, and scattered hematopoietic cells within the medullary cavity. Tends to be expressed at lower levels in the hypertrophic zone compared to trabeculae. Expressed in osteoblasts, osteoclasts and bone-marrow derived macrophages (PubMed:27330028).|||axon|||cytosol http://togogenome.org/gene/10090:Tas2r137 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0T3|||http://purl.uniprot.org/uniprot/Q7TQA7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5 (By similarity).|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Or10z1 ^@ http://purl.uniprot.org/uniprot/E9Q0Y7|||http://purl.uniprot.org/uniprot/Q7TRW4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptprq ^@ http://purl.uniprot.org/uniprot/P0C5E4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.|||In the inner ear of the early postnatal mouse, it is present in hair bundles in the cochlea and in the vestibule. Restricted to the hair bundles and not detected in any other cell type within the inner ear. Restricted to the basal region of the hair bundle (at protein level).|||Membrane|||Mice show rapid postnatal deterioration in cochlear hair-bundle structure, associated with smaller than normal transducer currents with otherwise normal adaptation properties, a progressive loss of basal-coil cochlear hair cells, and deafness.|||Phosphatidylinositol phosphatase required for auditory function. May act by regulating the level of phosphatidylinositol 4,5-bisphosphate (PIP2) level in the basal region of hair bundles. Can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. Has low tyrosine-protein phosphatase activity; however, the relevance of such activity in vivo is unclear. Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regulates the phosphorylation state of AKT1 by suppressing the phosphatidylinositol 3,4,5-trisphosphate (PIP3) level in MSCs and preadipocyte cells (By similarity). http://togogenome.org/gene/10090:Rpusd1 ^@ http://purl.uniprot.org/uniprot/Q8VCZ8 ^@ Similarity ^@ Belongs to the pseudouridine synthase RluA family. http://togogenome.org/gene/10090:Sema7a ^@ http://purl.uniprot.org/uniprot/Q9QUR8 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell membrane|||Highly expressed in activated T-cells (at protein level). Highest expression in brain. Lower in heart, thymus, spleen, testis and ovary. The expression increases in late embryonic and postnatal stages. Detected in T-cells.|||Interacts with PLXNC1 (By similarity). Interacts with ITGA1 and ITGB1.|||No visible phenotype. Mice display normal levels of lymphocytes in spleen, and normal activation of T-cells by antigenic stimuli. In contrast, production of pro-inflammatory cytokines by macrophages is much reduced. The effect on contact hypersensitivity and experimental autoimmune encephalomyelitis is controversial. Reduced size of the lateral olfactory tract.|||Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of pro-inflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes.|||The exact role in regulating T-cell function is under debate. According to (PubMed:16713976), SEMA7A-deficient mice are highly susceptible to contact hypersensitivity and experimental autoimmune encephalomyelitis. According to (PubMed:17377534) mice do not develop contact hypersensitivity, and are highly resistant to experimental autoimmune encephalomyelitis. http://togogenome.org/gene/10090:Trip11 ^@ http://purl.uniprot.org/uniprot/E9Q512 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Dock11 ^@ http://purl.uniprot.org/uniprot/A2AF47 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ 'Zizim' means 'spike' in Hebrew.|||Belongs to the DOCK family.|||Expressed in spleen, thymus, mesenteric lymph nodes (MLN), bone marrow and peripheral blood lymphocytes. Enriched in B-cells from germinal centers. Expressed in B-, T- and dendritic cells as well as Purkinje cells (PubMed:22494997, PubMed:25851601).|||Guanine nucleotide-exchange factor (GEF) that activates CDC42 by exchanging bound GDP for free GTP (PubMed:15710388, PubMed:16968698, PubMed:25851601). Required for marginal zone (MZ) B-cell development, is associated with early bone marrow B-cell development, MZ B-cell formation, MZ B-cell number and marginal metallophilic macrophages morphology (PubMed:25729399). Facilitates filopodia formation through the activation of CDC42 (PubMed:22494997).|||In dendritic cells, the expression is up-regulated by LPS and anti-Fc-gamma receptor.|||In spleen, expression is down-regulated in aged mice.|||Interacts with CDC42.|||Knockout mice are viable and fertile (PubMed:25729399). They have higher percentage of early bone marrow B-cells, but a reduced fraction of marginal zone B-cells. Their percentage of thymic CD4(+) T-cells is increased and they show an altered of morphologymarginal metallophilic macrophages (PubMed:25729399).|||The DOCKER domain is necessary for the GEF activity (PubMed:25851601, PubMed:15710388). The DOCKER domain mediates interaction with activated CDC42 in conjunction with residues 66-126 (PubMed:16968698). http://togogenome.org/gene/10090:Col23a1 ^@ http://purl.uniprot.org/uniprot/Q8K4G2 ^@ PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Homotrimer.|||Undergoes proteolytic cleavage by furin protease to yield a 60 kDa soluble form that forms a homotrimer and exhibits a low affinity interaction with heparin. http://togogenome.org/gene/10090:Cbx1 ^@ http://purl.uniprot.org/uniprot/P83917 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane.|||Homodimer (PubMed:10747027). Interacts directly with CHAF1A, EMSY, LBR, TIF1/TIF1A and TRIM28/TIF1B PXVXL motif via the chromoshadow domain (PubMed:8978696, PubMed:10562550, PubMed:10747027). Interacts directly with histone H3 methylated at 'Lys-9' via the chromo domain (PubMed:11571267). Interacts with SUV39H1, SETDB1, KMT5B and KMT5C (PubMed:10202156, PubMed:15145825). Interacts with PRDM6 (PubMed:16537907). Interacts with POGZ (By similarity). Interacts with CHAMP1 (By similarity). Interacts with INCENP (By similarity). Interacts with SGO1; the CBX1 homodimer binds to one molecule of SGO1 (By similarity). Interacts with LRIF1 (via PxVxL motif) (By similarity). Interacts with HDGFL2 (By similarity). Interacts with CHD3 (By similarity). Interacts with CHD4 (By similarity).|||In all adult and embryonic tissues.|||Not phosphorylated.|||Nucleus|||Ubiquitinated. http://togogenome.org/gene/10090:Gramd1c ^@ http://purl.uniprot.org/uniprot/Q8CI52 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (PubMed:30220461). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (PubMed:30220461). Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol (PubMed:30220461). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (PubMed:30220461). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (PubMed:30220461).|||Endoplasmic reticulum membrane|||GRAM domain binds phosphatidylserine in the PM and mediates protein recruitment to endoplasmic reticulum-plasma membrane contact sites (EPCS) in response to excess cholesterol in the PM.|||Highly expressed in the liver. Also found in the testis.|||VASt (VAD1 Analog of StAR-related lipid transfer) domain, also known as ASTER (Greek for star) domain is a sterol-binding domain. http://togogenome.org/gene/10090:Gm2411 ^@ http://purl.uniprot.org/uniprot/A0A571BDF8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Ncln ^@ http://purl.uniprot.org/uniprot/D3YU17|||http://purl.uniprot.org/uniprot/Q8VCM8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nicastrin family.|||Component of the back of Sec61 (BOS) complex, composed of NCLN/Nicalin, NOMO1 and TMEM147. The BOS complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO1 and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.|||Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (By similarity). May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning, via its interaction with NOMO (By similarity).|||Endoplasmic reticulum membrane|||May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning. http://togogenome.org/gene/10090:Ube2j2 ^@ http://purl.uniprot.org/uniprot/Q6P073 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Catalyzes the covalent attachment of ubiquitin to other proteins. Seems to function in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD) (PubMed:12082160). In cooperation with the GATOR2 complex, catalyzes 'Lys-6'-linked ubiquitination of NPRL2 (By similarity).|||Endoplasmic reticulum membrane|||In case of infection by the murid herpesvirus 4, its association with the viral E3 ligase K3 mediates ubiquitination of host surface class I (MHC-I) H-2D(b)/H2-D1 and H-2K(b)/H2-K1 molecules before they exit the endoplasmic reticulum, leading to their degradation by the ERAD system, thus blocking the immune detection of virus-infected cells. The complex formed with the murid herpesvirus 4 protein K3 mediates ubiquitination of lysine, as well as serine and threonine residues present in the cytoplasmic tail of surface class I molecules and promotes ubiquitination of hydroxylated serine or threonine residues via ester bonds instead of the classical isopeptide linkage.|||Interacts with murid herpesvirus 4 protein K3 (mK3). http://togogenome.org/gene/10090:Syngr4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0K3|||http://purl.uniprot.org/uniprot/D3Z3G3|||http://purl.uniprot.org/uniprot/Q9Z1L2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptogyrin family.|||Membrane http://togogenome.org/gene/10090:Smarce1 ^@ http://purl.uniprot.org/uniprot/O54941 ^@ Developmental Stage|||Domain|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B), and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin. May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (ACTB)(PubMed:17640523). Interacts with BRDT (By similarity). Also binds to the SRC/p160 family of histone acetyltransferases (HATs) composed of NCOA1, NCOA2, and NCOA3. Interacts with RCOR1/CoREST, NR3C1 and ZMIM2/ZIMP7 (By similarity).|||Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5-16.5 dpc.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:12110891). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (PubMed:17640523). Also specifically interacts with the CoREST corepressor resulting in repression of neuronal specific gene promoters in non-neuronal cells (By similarity). Required for the coactivation of estrogen responsive promoters by SWI/SNF complexes and the SRC/p160 family of histone acetyltransferases (HATs)(PubMed:12145209).|||Nucleus|||Sequencing errors.|||The HMG domain is essential for CD4 silencing and CD8 activation; mutation of this domain blocks thymus development.|||Ubiquitinated by TRIP12, leading to its degradation by the proteasome. Ubiquitination is prevented upon interaction between TRIP12 and SMARCC1 (By similarity). http://togogenome.org/gene/10090:Psmg1 ^@ http://purl.uniprot.org/uniprot/Q9JK23 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PSMG1 family.|||Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization (By similarity).|||Cytoplasm|||Degraded by the proteasome upon completion of 20S proteasome maturation.|||Endoplasmic reticulum|||Expressed at a fairly constant level throughout embryonic development.|||Forms a heterodimer with PSMG2. The PSMG1-PSMG2 heterodimer interacts directly with the PSMA5 and PSMA7 proteasome alpha subunits (By similarity).|||Highly expressed in testis with moderate expression in brain, liver and kidney and low levels in heart, skeletal muscle and pancreas. http://togogenome.org/gene/10090:Ric8a ^@ http://purl.uniprot.org/uniprot/Q3TIR3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synembryn family.|||Cell membrane|||Cytoplasm|||Death during early embryonic development. Heterozygous mice exhibit impaired spatial memory and decreased anxiety.|||During the early development (9.5-12.0 dpc) it is expressed in the developing nervous system such as the cranial ganglia, neural tube, sympathetic chain and dorsal root ganglia. Also found in the lens, vomeronasal organ and endolymphatic sac.|||Expressed in neurons and neurites of the CA1 and CA2 subregions of the hippocampus (at protein level). In adult brain, it is expressed in the neocortex, hippocampus and cerebellum as well as in the pineal gland and ependymal layer.|||Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein, possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex. Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation (By similarity).|||Interacts with GDP-bound G alpha proteins GNAI1, GNAO1 and GNAQ, and with GNA13 with lower affinity. Does not interact with G-alpha proteins when they are in complex with subunits beta and gamma. Interacts (via C-terminus) with RGS14; the interaction stimulates the dissociation of the complex between RGS14 and the active GTP-bound form of GNAI1. Interacts with NCS1; interaction is favored in the absence of Ca(2+) and myristoylation of NCS1 is not required (By similarity). http://togogenome.org/gene/10090:Zfp36 ^@ http://purl.uniprot.org/uniprot/P22893|||http://purl.uniprot.org/uniprot/Q3U3D2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to trigger ARE-containing mRNA deadenylation and decay processes (PubMed:20595389, PubMed:21078877). Part of a mRNA decay activation complex at least composed of poly(A)-specific exoribonucleases CNOT6, EXOSC2 and XRN1 and mRNA-decapping enzymes DCP1A and DCP2 (By similarity). Associates with the RNA exosome complex (By similarity). Interacts (via phosphorylated form) with 14-3-3 proteins; these interactions promote exclusion of ZFP36 from cytoplasmic stress granules in response to arsenite treatment in a MAPKAPK2-dependent manner and does not prevent CCR4-NOT deadenylase complex recruitment or ZFP36-induced ARE-containing mRNA deadenylation and decay processes (PubMed:15014438, PubMed:20595389). Interacts with 14-3-3 proteins; these interactions occur in response to rapamycin in an Akt-dependent manner (By similarity). Interacts with AGO2 and AGO4 (By similarity). Interacts (via C-terminus) with CNOT1; this interaction occurs in a RNA-independent manner and induces mRNA deadenylation (PubMed:21278420). Interacts (via N-terminus) with CNOT6 (By similarity). Interacts with CNOT6L (PubMed:21078877). Interacts (via C-terminus) with CNOT7; this interaction occurs in a RNA-independent manner, induces mRNA deadenylation and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389, PubMed:21278420). Interacts (via unphosphorylated form) with CNOT8; this interaction occurs in a RNA-independent manner and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:20595389). Interacts with DCP1A (By similarity). Interacts (via N-terminus) with DCP2 (By similarity). Interacts with EDC3 (By similarity). Interacts (via N-terminus) with EXOSC2 (By similarity). Interacts with heat shock 70 kDa proteins (By similarity). Interacts with KHSRP; this interaction increases upon cytokine-induced treatment (By similarity). Interacts with MAP3K4; this interaction enhances the association with SH3KBP1/CIN85 (By similarity). Interacts with MAPKAPK2; this interaction occurs upon skeletal muscle satellite cell activation (PubMed:25815583). Interacts with NCL (By similarity). Interacts with NUP214; this interaction increases upon lipopolysaccharide (LPS) stimulation (By similarity). Interacts with PABPC1; this interaction occurs in a RNA-dependent manner (PubMed:20595389, PubMed:21078877). Interacts (via hypophosphorylated form) with PABPN1 (via RRM domain and C-terminal arginine-rich region); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single-stranded poly(A) RNA-oligomer and in a p38 MAPK-dependent-manner and inhibits nuclear poly(A) tail synthesis (PubMed:22844456). Interacts with PAN2 (PubMed:21078877). Interacts (via C3H1-type zinc finger domains) with PKM (By similarity). Interacts (via C3H1-type zinc finger domains) with nuclear RNA poly(A) polymerase (PubMed:22844456). Interacts with PPP2CA; this interaction occurs in LPS-stimulated cells and induces ZFP36 dephosphorylation, and hence may promote ARE-containing mRNAs decay (PubMed:17170118). Interacts (via C-terminus) with PRR5L (via C-terminus); this interaction may accelerate ZFP36-mediated mRNA decay during stress (By similarity). Interacts (via C-terminus) with SFN; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts (via extreme C-terminal region) with SH3KBP1/CIN85 (via SH3 domains); this interaction enhances MAP3K4-induced phosphorylation of ZFP36 at Ser-58 and Ser-85 and does not alter neither ZFP36 binding to ARE-containing transcripts nor TNF-alpha mRNA decay (By similarity). Interacts with XRN1 (By similarity). Interacts (via C-terminus and Ser-178 phosphorylated form) with YWHAB; this interaction occurs in a p38/MAPKAPK2-dependent manner, increases cytoplasmic localization of ZFP36 and protects ZFP36 from Ser-178 dephosphorylation by serine/threonine phosphatase 2A, and hence may be crucial for stabilizing ARE-containing mRNAs (PubMed:14688255, PubMed:17170118). Interacts (via phosphorylated form) with YWHAE (PubMed:21078877). Interacts (via C-terminus) with YWHAG; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with YWHAH; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with YWHAQ; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Interacts with (via C-terminus) YWHAZ; this interaction occurs in a phosphorylation-dependent manner (PubMed:11886850). Does not interact with SH3KBP1 (PubMed:20221403). Interacts (via the 4EHP-binding motif) with EIF4E2; the interaction is direct (By similarity). Interacts (via P-P-P-P-G repeats) with GIGYF2; the interaction is direct (PubMed:26763119).|||Associates with the cytoplasmic CCR4-NOT deadenylase complex to trigger ARE-containing mRNA deadenylation and decay processes.|||Cytoplasm|||Cytoplasmic granule|||Expressed in skeletal muscle satellite cells (PubMed:25815583). Strongly expressed in differentiated adipocytes compared to preadipocytes (at protein level) (PubMed:22701344). Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed in heart, placenta, kidney, intestine, liver, lung, thymus, fat and spleen (PubMed:2204625, PubMed:1699942).|||Mice appear normal at birth, but within 1-8 weeks after birth they develop a complex syndrome of cachexia, arthritis, autoimmunity, myeloid hyperplasia and general inflammation (PubMed:8630730). Show precocious skeletal muscle satellite cell activation and increased satellite cell fusion into myofibers (PubMed:25815583). Show higher levels of tumor necrosis factor (TNF)-alpha mRNA and protein in macrophages and an excess of circulating TNF-alpha (PubMed:8630730, PubMed:9703499, PubMed:16508014). Show higher levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in macrophages and an excess of GM-CSF secretion upon lipopolysaccharide (LPS) stimulation (PubMed:10706852). Show higher levels of serine/threonine-protein kinase PLK3 expression in macrophages (PubMed:19188452). Show higher levels of interleukin IL2 expression in splenocytes and T lymphocytes and an excess of IL2 secretion upon T cell activation (PubMed:15634918). Show an increase in the stability of numerous mRNAs, such as TNF-alpha, GM-CSF, IL2 and PLK3 mRNAs (PubMed:9703499, PubMed:10706852, PubMed:15634918, PubMed:17030620, PubMed:19188452). Show an absence of ARE-containing transcript deadenylation (PubMed:10330172). Mice with a double knockout of ZFP36 and MAPKAPK2 show increased amounts of TNF in macrophages almost comparable to single ZFP36 knockout (PubMed:16508014).|||Nucleus|||P-body|||Phosphorylated (PubMed:11533235). Phosphorylation at serine and/or threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner (PubMed:11533235). Phosphorylated by MAPKAPK2 at Ser-52 and Ser-178; phosphorylation increases its stability and cytoplasmic localization, promotes binding to 14-3-3 adapter proteins and inhibits the recruitment of cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to the mRNA decay machinery, thereby inhibiting ZFP36-induced ARE-containing mRNA deadenylation and decay processes (PubMed:15014438, PubMed:14688255, PubMed:16508014, PubMed:16508015, PubMed:17170118, PubMed:20595389, PubMed:21078877). Phosphorylation by MAPKAPK2 does not impair ARE-containing RNA-binding (PubMed:20595389, PubMed:21078877). Phosphorylated in a MAPKAPK2- and p38 MAPK-dependent manner upon skeletal muscle satellite cell activation; this phosphorylation inhibits ZFP36-mediated mRNA decay activity, and hence stabilizes MYOD1 mRNA (PubMed:25815583). Phosphorylated by MAPK1 upon mitogen stimulation (PubMed:7768935, PubMed:14688255). Phosphorylated at Ser-58 and Ser-85; these phosphorylations increase in a SH3KBP1-dependent manner (By similarity). Phosphorylated at serine and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent manner (By similarity). Phosphorylation at Ser-52 may participate in the PKM-mediated degradation of ZFP36 in a p38 MAPK-dependent manner (By similarity). Dephosphorylated by serine/threonine phosphatase 2A at Ser-178 (PubMed:11533235, PubMed:17170118).|||The C3H1-type zinc finger domains are necessary for ARE-binding activity.|||Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination leads to proteasomal degradation through a p38 MAPK signaling pathway.|||Up-regulated during adipocyte differentiation (PubMed:17288565, PubMed:22701344). Up-regulated transiently in response to fibroblast growth factor FGF4 in a MAPK-dependent manner in embryonic stem cells (ESCs) (PubMed:24733888). Up-regulated by interferons and/or lipopolysaccharide (LPS) in a STAT1- and p38 MAPK-dependent manner (PubMed:11533235, PubMed:16514065, PubMed:16508014, PubMed:16508015). Down-regulated in muscle satellite cells upon muscle injury (at protein level) (PubMed:25815583). Up-regulated by various mitogens (PubMed:7559666). Up-regulated by LPS and TNF-alpha (PubMed:9703499). Up-regulated by interferon IFN-gamma and/or LPS in a STAT1- and p38 MAPK-dependent manner (PubMed:15187092, PubMed:16514065). Up-regulated during adipocyte differentiation (PubMed:22701344). Up-regulated in keratinocytes during epidermal repair after wound healing (PubMed:20166898). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583).|||Zinc-finger RNA-binding protein that destabilizes numerous cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:10330172, PubMed:10706852, PubMed:10805719, PubMed:15014438, PubMed:15187092, PubMed:15634918, PubMed:17030620, PubMed:19188452, PubMed:20595389, PubMed:21078877, PubMed:22701344, PubMed:27193233). Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:21278420). Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation (PubMed:21278420). Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs (PubMed:21278420). Self regulates by destabilizing its own mRNA (PubMed:15187092, PubMed:17288565). Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:11533235, PubMed:15187092, PubMed:16508014, PubMed:17288565, PubMed:17971298, PubMed:20595389, PubMed:21078877, PubMed:21278420, PubMed:22701344, PubMed:27193233). Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor (TNF)-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-induced macrophages (PubMed:8630730, PubMed:9703499, PubMed:15014438, PubMed:16514065). Also plays a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response (By similarity). Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia (By similarity). Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA (By similarity). Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA (PubMed:25815583). Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs (By similarity). Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA (miRNA) targeting ARE-containing mRNAs (By similarity). May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro (By similarity). Involved in the delivery of target ARE-mRNAs to processing bodies (PBs) (By similarity). In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing (PubMed:22844456). Negatively regulates nuclear poly(A)-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages (PubMed:22844456). Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion (PubMed:15967811). Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis (By similarity). Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells (By similarity).|||Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes. Binds to 3'-UTR ARE of numerous mRNAs. http://togogenome.org/gene/10090:Or1p1 ^@ http://purl.uniprot.org/uniprot/B1ARL3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sp140 ^@ http://purl.uniprot.org/uniprot/Q6NSQ5 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Slitrk5 ^@ http://purl.uniprot.org/uniprot/Q810B7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SLITRK family.|||In the adult, significant expression is detected only in the brain. In the embryo, expressed in the subventricular zone, cortical plate, pyramidal layer of hippocampus, thalamus and hypothalamus.|||Membrane|||Suppresses neurite outgrowth. http://togogenome.org/gene/10090:Or3a1b ^@ http://purl.uniprot.org/uniprot/Q8VFX6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rad9a ^@ http://purl.uniprot.org/uniprot/Q9Z0F6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rad9 family.|||Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. RAD9A possesses 3'->5' double stranded DNA exonuclease activity (By similarity).|||Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. RAD9A interacts with BCL2L1, FEN1, PRKCD, RAD9B, HUS1, RAD1, ABL1, RPA1 and RPA2. Interacts with DNAJC7 and RHNO1 (By similarity). Interacts with ATAD5.|||Constitutively phosphorylated on serine and threonine amino acids in absence of DNA damage. Hyperphosphorylated by PRKCD and ABL1 upon DNA damage. Its phosphorylation by PRKCD may be required for the formation of the 9-1-1 complex (By similarity).|||Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Nucleus http://togogenome.org/gene/10090:Lce3f ^@ http://purl.uniprot.org/uniprot/Q6PAI4 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Gm21677 ^@ http://purl.uniprot.org/uniprot/O35698 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with splicing factor proteins SFRS3/SRP20, TRA2B/SFRS10, KHDRBS1/SAM68 and KHDRBS3.|||Nucleus|||Only expressed in spermatogonia and early spermatocytes, suggesting that expression is inactivated in the XY body during meiosis.|||Overexpression of Rbmy proteins in mice carrying the Y(d1) deletion that removes most of the multi-copy Rbmy gene cluster does not have any effect and fails to reduce the frequency of abnormal sperm. These results raize the question of the role of Rbmy proteins in sperm development.|||RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs.|||Testis-specific.|||The RBMY1 proteins are encoded by repeated regions of the Y chromosome. The exact number of functional copies is unclear and may vary between individuals, and some of them may represent pseudogenes. http://togogenome.org/gene/10090:Bcl6 ^@ http://purl.uniprot.org/uniprot/P41183 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-380 by EP300 which inhibits the interaction with NuRD complex and the transcriptional repressor function. Deacetylated by HDAC- and SIR2-dependent pathways.|||Detected in the cerebral cortex from 12.5 dpc until birth, with highest levels in the frontal and parietal parts of the neocortex than the occipital parts.|||Expressed at least in germinal center B-cells of spleen.|||Homodimer. Interacts (via BTB domain) with the corepressors BCOR, NCOR1 and SMRT/NCOR2; the interactions are direct. Forms preferably ternary complexes with BCOR and SMRT/NCOR2 on target gene promoters but, on enhancer elements, interacts with SMRT/NCOR2 and HDAC3 to repress proximal gene expression. Interacts with histone deacetylases HDAC2, HDAC5 and HDAC9 (via the catalytic domain). Interacts with ZBTB7 and BCL6B. Interacts with SCF(FBXO11) complex; the interaction is independent of phosphorylation and promotes ubiquitination. Interacts (when phosphorylated) with PIN1; the interaction is required for BCL6 degradation upon genotoxic stress. Interacts with ZBTB17; inhibits ZBTB17 transcriptional activity. Interacts with CTBP1, autoinhibits its transcriptional expression. Interacts with NOTCH1 NCID and SIRT1; leads to a epigenetic repression of selective NOTCH1-target genes. Interacts (nor via BTB domain neither acetylated) with the NuRD complex components CHD4, HDAC1, MBD3 and MTA3; the interaction with MTA3 inhibits BCL6 acetylation and is required for BCL6 transpriptional repression.|||Interaction with corepressors through the BTB domain is needed to facilitate the rapid proliferation and survival of GC B-cells but is not involved in the T(FH) formation and BCL6-mediated suppression of T(H)2 and T(H)17 differentiation required for GC formation.|||More than 50% of lethality by 6 weeks of age. Mice have infiltrates of inflammatory cells in their lungs, as well as multinodular lesions with eosinophil infiltrations into the spleen, significantly more T(H)2 and T(H)17 cells and up-regulated levels of inflammtaroy chemokines in macrophages, but, express low levels of memory CD8(+) T-cells and, in spleen, GC B and T(FH) cells are both undetectable. B-cells express 10-fold lower levels of surface IgM than control littermates and macrophages divide faster. From 12.5 dpc to at least 21 days after birth, animals have reduced size of the cerebral hemispheres and a reduced thickness of the frontal and parietal cortex with all the cortical layers affected. At 12.5 and 15.5 dpc, marked reduction of cell-cycle exit indicating defective transition from neural progenitor Cells to postmitotic neurons.|||Nucleus|||Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-334 and Ser-344. Phosphorylated by ATM in response to genotoxic stress. Phosphorylation induces its degradation by ubiquitin/proteasome pathway.|||Polyubiquitinated. Polyubiquitinated by SCF(FBXO11), leading to its degradation by the proteasome. Ubiquitinated by the SCF(FBXL17) complex, leading to its degradation by the proteasome: ubiquitination by the SCF(FBXL17) complex takes place when aberrant BTB domain dimers are formed.|||Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53-dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation. http://togogenome.org/gene/10090:Oosp3 ^@ http://purl.uniprot.org/uniprot/G5E8D7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PLAC1 family.|||Oocyte-specific.|||Secreted http://togogenome.org/gene/10090:Exoc2 ^@ http://purl.uniprot.org/uniprot/Q9D4H1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC5 family.|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Interacts with RALA through the TIG domain.|||Midbody ring|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8 (PubMed:26582389). Interacts with EXOC3L1 (PubMed:18480549). Interacts with GNEFR/DELGEF; this interaction occurs only in the presence of magnesium or manganese and is stimulated by dCTP or GTP (By similarity). Interacts with RALA and RALB (By similarity) (PubMed:18480549). Interacts with ARL13B; regulates ARL13B localization to the cilium membrane. http://togogenome.org/gene/10090:Rmdn2 ^@ http://purl.uniprot.org/uniprot/Q8BSE0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RMDN family.|||Cytoplasm|||Interacts with microtubules.|||Membrane|||spindle|||spindle pole http://togogenome.org/gene/10090:4930550C14Rik ^@ http://purl.uniprot.org/uniprot/Q9D4W2 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an inhibitor of mitochondrial fission. Interacts with MFF and prevents DNM1L recruitment to mitochondria, promoting a more fused mitochondrial network.|||Can homodimerize (PubMed:30059978). Interacts with MFF; the interaction inhibits MFF interaction with DNM1L (PubMed:30059978).|||Enriched in the pancreatic beta cell and the testis and is expressed at low levels in other tissues tested.|||Mitochondrion outer membrane|||cytosol http://togogenome.org/gene/10090:2410004B18Rik ^@ http://purl.uniprot.org/uniprot/Q9CWU4 ^@ Similarity ^@ Belongs to the UPF0690 family. http://togogenome.org/gene/10090:Fam47c ^@ http://purl.uniprot.org/uniprot/Q14BE7 ^@ Similarity ^@ Belongs to the FAM47 family. http://togogenome.org/gene/10090:2310022A10Rik ^@ http://purl.uniprot.org/uniprot/Q8R3Y5 ^@ Miscellaneous ^@ Due to an intron retention. http://togogenome.org/gene/10090:Acer1 ^@ http://purl.uniprot.org/uniprot/Q8R4X1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alkaline ceramidase family.|||Endoplasmic reticulum ceramidase that catalyzes the hydrolysis of ceramides into sphingosine and free fatty acids at alkaline pH (PubMed:12783875). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:12783875). Exhibits a strong substrate specificity towards the natural stereoisomer of ceramides with D-erythro-sphingosine as a backbone and has a higher activity towards very long-chain unsaturated fatty acids like the C24:1-ceramide (PubMed:12783875). May also hydrolyze dihydroceramides to produce dihydrosphingosine (By similarity). ACER1 is a skin-specific ceramidase that regulates the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes and more generally plays an important role in skin homeostasis (PubMed:27126290, PubMed:29056331).|||Endoplasmic reticulum membrane|||Highly expressed in skin. Weakly or not expressed in other tissues (PubMed:12783875). Expressed by granular layer of interfollicular epidermis, sebaceous glands and infundibulum (PubMed:29056331).|||Homozygous knockout mice are viable and fertile, with a normal lifespan but display several postnatal skin phenotypes (PubMed:27126290, PubMed:29056331). It includes an increase in total ceramide levels in the dorsal skin, tail epidermis and dermis (PubMed:27126290, PubMed:29056331). This is associated with hair shafts and sebaceous glands abnormalities, cyclic alopecia, a progressive loss of hair follicle stem cells, hyperproliferation, inflammation and abnormal differentiation of the epidermis and results in increased transepidermal water loss and reduction of fat content during aging (PubMed:27126290, PubMed:29056331).|||Inhibited by sphingosine (PubMed:12783875). Inhibited by Mn(2+), Zn(2+), and Cu(2+) in a dose-dependent manner (PubMed:12783875). Slightly activated by Ca(2+) in a dose-dependent manner (PubMed:12783875). http://togogenome.org/gene/10090:Ttyh3 ^@ http://purl.uniprot.org/uniprot/Q6P5F7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tweety family.|||Cell membrane|||Expressed in excitable tissues. Expressed in the brain, heart, skeletal muscle, colon, spleen, kidney and peripheral blood leukocytes. Also expressed in fat, the pancreas, thymus, and uterus.|||N-glycosylated.|||Probable large-conductance Ca(2+)-activated chloride channel. May play a role in Ca(2+) signal transduction (By similarity). http://togogenome.org/gene/10090:Krt90 ^@ http://purl.uniprot.org/uniprot/E9Q1Z0|||http://purl.uniprot.org/uniprot/Q8BIS2 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Tspan13 ^@ http://purl.uniprot.org/uniprot/Q9D8C2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||Membrane http://togogenome.org/gene/10090:Slc6a21 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSD2|||http://purl.uniprot.org/uniprot/Q3V0K1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Membrane http://togogenome.org/gene/10090:Gpr139 ^@ http://purl.uniprot.org/uniprot/A0A142CHG4|||http://purl.uniprot.org/uniprot/Q80UC8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed almost exclusively in the brain. Abundantly expressed in the ventrolateral region of caudate putamen, the habenular nucleus, the zona incerta, and the medial mammillary nucleus.|||Membrane|||Orphan receptor. Seems to act through a G(q/11)-mediated pathway. http://togogenome.org/gene/10090:Agpat2 ^@ http://purl.uniprot.org/uniprot/Q059U0|||http://purl.uniprot.org/uniprot/Q8K3K7 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.|||Down-regulated in the heart by clofibrate, a PPAR-alpha agonist.|||Endoplasmic reticulum membrane|||Expressed at high levels in the liver, at intermediate levels in the kidney, gut, heart and skeletal muscles. Undetectable in brain and spleen.|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate. http://togogenome.org/gene/10090:Scrt2 ^@ http://purl.uniprot.org/uniprot/Q8BTH6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the snail C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Smc3 ^@ http://purl.uniprot.org/uniprot/Q1HL32|||http://purl.uniprot.org/uniprot/Q3TMK9|||http://purl.uniprot.org/uniprot/Q9CW03 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-105 and Lys-106 by ESCO1 is important for genome stability and S phase sister chromatid cohesion. Regulated by DSCC1, it is required for processive DNA synthesis, coupling sister chromatid cohesion establishment during S phase to DNA replication (By similarity). Deacetylation by HDAC8, regulates release of the cohesin complex from chromatin (By similarity).|||Belongs to the SMC family. SMC3 subfamily.|||Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement.|||Chromosome|||Forms a heterodimer with SMC1A or SMC1B in cohesin complexes (PubMed:11564881). Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their SMC hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21. Also found in meiosis-specific cohesin complexes. Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN. Interacts with PDS5A and WAPL; regulated by SMC3 acetylation. Interacts with NUMA1, and forms a ternary complex with KIF3B and KIFAP3, suggesting a function in tethering the chromosomes to the spindle pole and a function in chromosome movement. Interacts with SYCP2 and RPGR. Interacts (via SMC hinge domain) with KIAA1328 (via N- and C-terminal domains). Interacts with DDX11. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (By similarity). Interacts with MXI1, MXD3 and MXD4 (PubMed:9528857). Interacts with STAG3 (PubMed:11483963). Interacts with the NuRD complex component HDAC2; the interaction is direct (By similarity).|||Nucleus|||Phosphorylated at Ser-1083 in a SPO11-dependent manner.|||Spermatocytes (at protein level). Widely expressed, with higher expression in testis and brain.|||The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1A or SMC1B, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure (By similarity).|||Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation.|||Was originally isolated as a proteoglycan protein (explaining its name). Although not excluded, such secreted function is not clear.|||centromere http://togogenome.org/gene/10090:Eya1 ^@ http://purl.uniprot.org/uniprot/F6YST4|||http://purl.uniprot.org/uniprot/P97767|||http://purl.uniprot.org/uniprot/Q6PAJ8|||http://purl.uniprot.org/uniprot/Q8C9D0 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A spontaneous mutation leading to decreased Eya1 expression gives rise to the Eya1-bor phenotype. It is characterized by circling behavior and deafness, due to gross morphological abnormalities of the inner ear, and dysmorphic or missing kidneys. This autosomal recessive trait resembles human branchio-oto-renal (BOR) syndrome.|||Belongs to the HAD-like hydrolase superfamily. EYA family.|||Binds 1 Mg(2+) ion per subunit.|||Complete perinatal lethality in homozygotes, due to severe craniofacial and skeletal defects, combined with an absence of thymus, kidneys, parotid glands and ears. Mice present multiple skeletal defects in skull, neck, rib and pelvic girdle, but no major defects in muscle development. Otic anomalies involve the inner, middle and outer ears, with malformed auricles and eardrums, malformations of the incus, malleus, and stapes, while the tympanic cavity never formed. Likewise, mice display an absence of inner ear structures. Heterozygotes present milder symptoms with low penetrance, including renal defects, similar to human BOR (branchio-oto-renal) syndrome. Increased apoptosis and loss of renal tubules seen in the developing kidney with increased immunostaining for 'Ser-139' phosphorylated H2AX. Mice lacking both Six1 and Eya1 show defects in kidney development, complete absence of hypaxial muscle, severe reduction in epaxial muscle and a 5-10-fold by volume smaller pituarity than the wild-type gland. Mice lacking both Eya1 and Eya2 display complete embryonic lethality, due to severe defects in muscle development, including the absence of a diaphragm and of ventral hypaxial muscles of the trunk and the complete absence of muscles in forelimbs and hindlimbs, similar to the phenotype of mice lacking both Six1 and Six4. While Six1 is normally expressed in these mice, it does not active transcription from cognate promoter elements, and does not activate transcription of Pax3.|||Cytoplasm|||Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose.|||Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:10490620). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19234442). Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis (PubMed:14628042). Has also phosphatase activity with proteins phosphorylated on Ser and Thr residues (in vitro). Required for normal embryonic development of the craniofacial and trunk skeleton, kidneys and ears (PubMed:10471511). Together with SIX1, it plays an important role in hypaxial muscle development; in this it is functionally redundant with EYA2 (PubMed:17098221).|||Nucleus|||Probably interacts with SIX2, SIX4 and SIX5. Interacts with H2AX in response to DNA damage. Interacts with SIX3; promotes EYA1 translocation to the nucleus.|||Sumoylated with SUMO1. http://togogenome.org/gene/10090:Elmo1 ^@ http://purl.uniprot.org/uniprot/Q8BPU7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts directly with the SH3-domain of DOCK1 via its SH3-binding site. Probably forms a heterotrimeric complex with DOCK1 and RAC1 (By similarity). Interacts with PLEKHG6. Interacts with HCK (via SH3 domain) (By similarity). Interacts with ADGRB1 (PubMed:17960134). Interacts with ADGRB3 (By similarity). Interacts with DOCK5 (PubMed:27505886).|||Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1 (By similarity).|||Phosphorylated by HCK. http://togogenome.org/gene/10090:Sohlh2 ^@ http://purl.uniprot.org/uniprot/Q9D489 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Forms both hetero- and homodimers with SOHLH1.|||In the embryonic gonads it is expressed as early as 13.5 dpc and later. In 3-day-old postnatal ovaries, it is expressed within oocytes in germ cell clusters and primordial follicles. In the adult, it is expressed only in small follicles, primary primordial and primary follicles. In testis, it is exclusively present in spermatogonia. Present at postnatal day 5, when spermatogonia stem cells differentiate into type A spermatogonia. Absent in Sertoli cells or spermatocytes (at protein level). Expressed in the germline as early as 12.5 dpc and precedes SOHLH1 protein expression, which occurred circa 15.5 dpc. SOHLH1 appearance at 15.5 dpc correlates with SOHLH2 translocation from the cytoplasm into the nucleus (PubMed:28504655).|||Knockout mice are infertile. Infertility could not be rescued by SOHLH1 or SOHLH2 transgene expression due to a lack of expression of either genes in rescued animals.|||Nucleus|||Preferentially expressed in the adult ovary and testis. Expressed in the majority of spermatogonia in adult animals, but not in the most undifferentiated spermatogonial population (PubMed:22056784).|||Transcription regulator of both male and female germline differentiation. Suppresses genes involved in spermatogonial stem cells maintenance, and induces genes important for spermatogonial differentiation (PubMed:22056784). Coordinates oocyte differentiation without affecting meiosis I (PubMed:28504655).|||Up-regulated in mice lacking Sohlh1. http://togogenome.org/gene/10090:Pip ^@ http://purl.uniprot.org/uniprot/P02816|||http://purl.uniprot.org/uniprot/Q3UU48 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIP family.|||Lacrimal and submaxillary glands.|||Monomer. Interacts with AZGP1 (By similarity).|||Monomer. Interacts with AZGP1.|||Secreted http://togogenome.org/gene/10090:Tjp2 ^@ http://purl.uniprot.org/uniprot/A0A3B2WCN9|||http://purl.uniprot.org/uniprot/Q9Z0U1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAGUK family.|||Cell membrane|||Homodimer (By similarity). Interacts (via PDZ2 domain) with TJP1/ZO1 (via PDZ2 domain) (PubMed:10026224). Interacts with UBN1 (By similarity). Interacts with SCRIB (By similarity). Interacts with OCLN (PubMed:10026224). Interacts with SAFB in the nucleus (PubMed:12403786). Interacts with USP53 (via the C-terminal region) (PubMed:26609154). Interacts with claudins, including CLDN1, CLDN2, CLDN3, CLDN5 and CLDN7 (By similarity). Interacts with CLDN18 (PubMed:22437732). Interacts (via N-terminus) with CTNNA1 (PubMed:10026224).|||Membrane|||Nucleus|||Plays a role in tight junctions and adherens junctions (PubMed:10026224). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (PubMed:22437732).|||tight junction http://togogenome.org/gene/10090:Garin2 ^@ http://purl.uniprot.org/uniprot/D3YV92 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GARIN family.|||Expressed in testis (at protein level).|||Expression increases from 3 weeks to 6 months (PubMed:29025071). In mouse testis, mainly localized in the cytoplasm of round spermatids and elongated spermatids. In the cap phase, remains close to the acrosomes but begins to migrate to other regions around the nuclei. As spermiogenesis progresses, further separates from the acrosomes. In the acrosome phase, while the acrosomes formed hook-like structures and move toward one end of the nuclei, GARIN2 moveS to the opposite end. In the maturation phase, moves to the end opposite to the acrosomes and, at the end of spermiogenesis, is removed to the residue body together with most of the other cytosolic components. Finally, in caudal sperm, is retained in sperm flagella. In mature sperm, GARIN2 localizes in the midpiece of flagella (PubMed:29025071).|||Interacts with CALM1.|||Seems to play a role in sperm motility.|||flagellum http://togogenome.org/gene/10090:Pin4 ^@ http://purl.uniprot.org/uniprot/Q9CWW6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PpiC/parvulin rotamase family. PIN4 subfamily.|||Cytoplasm|||Found in pre-ribosomal ribonucleoprotein (pre-rRNP) complexes.|||Involved as a ribosomal RNA processing factor in ribosome biogenesis. Binds to tightly bent AT-rich stretches of double-stranded DNA (By similarity).|||Phosphorylated. Phosphorylation occurs both in the nucleus and the cytoplasm. Phosphorylation at Ser-19 does not affect its PPIase activity but is required for nuclear localization, and the dephosphorylation is a prerequisite for the binding to DNA. The unphosphorylated form associates with the pre-rRNP complexes in the nucleus (By similarity).|||nucleolus|||spindle http://togogenome.org/gene/10090:Lrrc51 ^@ http://purl.uniprot.org/uniprot/G5E8I1|||http://purl.uniprot.org/uniprot/Q9DAK8 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Widely expressed in adult and embryonic tissues. Expressed in the developing choroid plexus from 12.5 dpc and in the epithelium of the developing airway tract from 14.5 dpc. Also expressed in the postnatal inner ear. http://togogenome.org/gene/10090:Muc5ac ^@ http://purl.uniprot.org/uniprot/E9PWB6 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Tas2r136 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0W1|||http://purl.uniprot.org/uniprot/Q7TQA8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Ccnyl1 ^@ http://purl.uniprot.org/uniprot/E9Q226 ^@ Similarity ^@ Belongs to the cyclin family. Cyclin Y subfamily. http://togogenome.org/gene/10090:Lamtor2 ^@ http://purl.uniprot.org/uniprot/Q9JHS3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (By similarity). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (By similarity). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (By similarity). Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2 (PubMed:15263099).|||Belongs to the GAMAD family.|||Late endosome membrane|||Lysosome membrane|||Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 (PubMed:15016825, PubMed:15263099, PubMed:15740743, PubMed:19177150). LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer (PubMed:15016825, PubMed:15263099, PubMed:15740743, PubMed:19177150). The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability (PubMed:15016825, PubMed:15263099, PubMed:15740743, PubMed:19177150). The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (By similarity). Interacts with LAMTOR1 and LAMTOR3; the interaction is direct. Interacts with MAPK1 and MAP2K1 (PubMed:11266467). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Gm7030 ^@ http://purl.uniprot.org/uniprot/Q0WXH6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Gm2012 ^@ http://purl.uniprot.org/uniprot/B1B0R1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Gm2042 ^@ http://purl.uniprot.org/uniprot/Q5RJV9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Or2ag20 ^@ http://purl.uniprot.org/uniprot/Q9EPF6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nup62 ^@ http://purl.uniprot.org/uniprot/Q5FWJ9|||http://purl.uniprot.org/uniprot/Q63850 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleoporin NSP1/NUP62 family.|||Component of the p62 complex, a complex at least composed of NUP62, NUP54, and NUP58. Interacts with NUP88. Interacts with NUTF2. Interacts with HIKESHI. Interacts with OSBPL8. Interacts with CAPG. Interacts with SAS6 and TUBG1 at the centrosome. Interacts with MCM3AP (By similarity).|||Contains FG repeats.|||Essential component of the nuclear pore complex. The N-terminal is probably involved in nucleocytoplasmic transport. The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex. Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation. It might be involved in protein recruitment to the centrosome after nuclear breakdown.|||Nucleus envelope|||O-glycosylated.|||The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.|||centrosome|||nuclear pore complex|||spindle pole http://togogenome.org/gene/10090:Thumpd3 ^@ http://purl.uniprot.org/uniprot/P97770 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily.|||Cytoplasm|||Interacts with TRMT112; the interaction is direct and is required for THUMPD3 methyltransferase activity.|||Methyltransferase which catalyzes the formation of N(2)-methylguanosine at position 6 in a broad range of tRNA substrates containing the characteristic 3'-CCA terminus of mature tRNAs (By similarity). Also catalyzes the formation of N(2)-methylguanosine at position 7 of tRNA(Trp) (By similarity). Requires the methyltransferase adapter protein TRM112 for tRNA methyltransferase activity (By similarity).|||Ubiquitously expressed (PubMed:9108056). Abundantly expressed in the testis, also expressed in the brain, heart, kidney, liver, lung, muscle and spleen (PubMed:34669960). http://togogenome.org/gene/10090:Ganc ^@ http://purl.uniprot.org/uniprot/A2AQJ8|||http://purl.uniprot.org/uniprot/Q8BVW0 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the glycosyl hydrolase 31 family.|||Has alpha-glucosidase activity.|||May be due to an intron retention. http://togogenome.org/gene/10090:Trmu ^@ http://purl.uniprot.org/uniprot/Q9DAT5 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MnmA/TRMU family.|||Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble position. ATP is required to activate the C2 atom of the wobble base.|||During the reaction, ATP is used to activate the C2 atom of U34 by adenylation. After this, the persulfide sulfur on the catalytic cysteine is transferred to the C2 atom of the wobble base (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards the activated C2 atom on U34. Subsequently, a transient disulfide bond is formed between the two active site cysteine residues (By similarity).|||Mitochondrion|||Was originally thought to be a 5-methylaminomethyl-2-methyltransferase involved in tRNA modification.|||Widely expressed but most abundant in tissues with high metabolic rate including heart, liver and brain. Expression is low in spleen, testis, lung and skeletal muscle. Also expressed in inner ear. http://togogenome.org/gene/10090:Zdhhc19 ^@ http://purl.uniprot.org/uniprot/Q810M5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DHHC palmitoyltransferase family.|||Golgi apparatus membrane|||Palmitoyltransferase that mediates palmitoylation of RRAS, leading to increased cell viability.|||The DHHC domain is required for palmitoyltransferase activity.|||perinuclear region http://togogenome.org/gene/10090:Sdr39u1 ^@ http://purl.uniprot.org/uniprot/Q5M8N4 ^@ Function|||Similarity ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family. SDR39U1 subfamily.|||Putative NADP-dependent oxidoreductase. http://togogenome.org/gene/10090:Calcoco1 ^@ http://purl.uniprot.org/uniprot/Q8CGU1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CALCOCO family.|||Cytoplasm|||Expressed in all tissues examined except spleen, with high levels of expression in the heart and kidney.|||Functions as a coactivator for aryl hydrocarbon and nuclear receptors (NR). Recruited to promoters through its contact with the N-terminal basic helix-loop-helix-Per-Arnt-Sim (PAS) domain of transcription factors or coactivators, such as NCOA2. During ER-activation acts synergistically in combination with other NCOA2-binding proteins, such as EP300, CREBBP and CARM1. Involved in the transcriptional activation of target genes in the Wnt/CTNNB1 pathway. Functions as a secondary coactivator in LEF1-mediated transcriptional activation via its interaction with CTNNB1. Coactivator function for nuclear receptors and LEF1/CTNNB1 involves differential utilization of two different activation regions. In association with CCAR1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781).|||Nucleus|||Part of a calphoglin complex consisting of CALCOCO1, PPA1 and PGM (By similarity). Interacts with the bHLH-PAS domains of GRIP1, AHR and ARNT. Interacts with CTNNB1 via both its N- and C-terminal regions. Interacts with EP300. Interacts with CCAR1 (via N-terminus) and GATA1.|||Recruitment by nuclear receptors is accomplished by the interaction of the coiled-coiled domain with p160 coactivators.|||The C-terminal activation region (AD) is used for downstream signaling. Seems to be essential for coactivator function with nuclear receptors and with the aryl hydrocarbon receptor.|||The N-terminal activation region (AD) is necessary and sufficient for synergistic activation of LEF1-mediated transcription by CTNNB1. Contains a EP3000 binding region which is important for synergistic cooperation. http://togogenome.org/gene/10090:Gsdmc4 ^@ http://purl.uniprot.org/uniprot/A0A679B0N4|||http://purl.uniprot.org/uniprot/Q3TR54 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage by CASP8 relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-C4, N-terminal) that initiates pyroptosis.|||Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.|||Membrane|||Pore-forming protein that causes membrane permeabilization and pyroptosis. Produced by the cleavage of gasdermin-D by caspase CASP8 in response to death signals. After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis.|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C4, N-terminal) following cleavage by caspase CASP8.|||This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C4, N-terminal) binds to membranes and forms pores, triggering pyroptosis.|||cytosol http://togogenome.org/gene/10090:Map3k4 ^@ http://purl.uniprot.org/uniprot/O08648 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.|||Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with CDC42 (PubMed:9079650). Interacts with TRAF4; this promotes homodimerization (PubMed:16157600). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1 (PubMed:15262978). Interacts with GADD45 and MAP2K6 (By similarity). Interacts with ZFP36; this interaction enhances the association with SH3KBP1/CIN85. Interacts with SH3KBP1; this interaction enhances the association with ZFP36 (By similarity).|||N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1494 (By similarity).|||Widely expressed. High expression was found in skeletal muscle, kidney, testis followed by heart brain and lung. Low expression was found in spleen.|||perinuclear region http://togogenome.org/gene/10090:Mixl1 ^@ http://purl.uniprot.org/uniprot/Q9WUI0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||By TGF-beta. Regulated by Nodal in mesendoderm morphogenesis. Regulated by FOXH1, which acts as a negative regulator by recruiting GSC to promoter during early development.|||Expressed in the primitive streak of the gastrulating embryo, and marks cells destined to form mesoderm and endoderm. Present in differentiating embryonic stem cells (at protein level).|||Initially expressed in visceral endoderm and becomes restricted to primitive streak and nascent mesoderm at gastrulation. This includes the hemangioblast, a precursor of hematopoietic and vascular stem cells. At 5.5 dpc, it is expressed symmetrically in the visceral endoderm but by 6.0 dpc this expression is noticeably asymmetric. At 6.5 dpc, expression is restricted to the nascent primitive streak and persists in the primitive streak through 7.5-9.5 dpc, marking those cells fated to form extra-embryonic and lateral mesoderm.|||Mice display defects in mesendoderm morphogenesis and patterning during development. Embryos show a marked thickening of the primitive streak. By the early somite stage, embryonic development is arrested, with the formation of abnormal head folds, foreshortened body axis, absence of heart tube and gut, deficient paraxial mesoderm, and an enlarged midline tissue mass that replaces the notochord. Development of extra-embryonic structures is generally normal except that the allantois is often disproportionately large for the size of the mutant embryo.|||Nucleus|||Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood, by acting early in the recruitment and/or expansion of mesodermal progenitors to the hemangioblastic and hematopoietic lineages. Also involved in the morphogenesis of the heart and the gut during embryogenesis. Acts as a negative regulator of brachyury expression. http://togogenome.org/gene/10090:Ncapg ^@ http://purl.uniprot.org/uniprot/E9PWG6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CND3 (condensin subunit 3) family.|||Chromosome http://togogenome.org/gene/10090:Hspb6 ^@ http://purl.uniprot.org/uniprot/Q5EBG6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small heat shock protein (HSP20) family.|||Cytoplasm|||Homodimer. Small heat shock proteins form high molecular mass oligomers containing variable number of monomers; these oligomers display a very flexible quaternary structure easily exchanging their subunits. Heterooligomer with HSPB1; formed through oligomerization of HSPB1:HSBP6 dimers; subunit exchange leads to formation of at least two different heterooligomeric complexes, differing in variable quantities of HSPB1 and HSPB6 homodimers in addition to HSPB1:HSPB6 heterodimers. Heterooligomer with CRYAB; large heterooligomers consist of CRYAB homodimers and HSPB5:HSPB6 heterodimers but lacking HSPB6 homodimers. Interacts with BAG3. Interacts (phosphorylated) with YWHAZ. Interacts with PDE4A and PDE4D; required for maintenance of the non-phosphorylated state of HSPB6 under basal conditions. Interacts with KDR. Interacts with PRKD1.|||Nucleus|||Phosphorylated at Ser-16 by PKA and probably PKD1K; required to protect cardiomyocytes from apoptosis.|||Secreted|||Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Seems to have versatile functions in various biological processes. Plays a role in regulating muscle function such as smooth muscle vasorelaxation and cardiac myocyte contractility. May regulate myocardial angiogenesis implicating KDR. Overexpression mediates cardioprotection and angiogenesis after induced damage. Stabilizes monomeric YWHAZ thereby supporting YWHAZ chaperone-like activity. http://togogenome.org/gene/10090:Or2w1 ^@ http://purl.uniprot.org/uniprot/Q7TQT8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rapgefl1 ^@ http://purl.uniprot.org/uniprot/Q68EF8 ^@ Function|||Sequence Caution ^@ Aberrant splicing.|||Probable guanine nucleotide exchange factor (GEF). http://togogenome.org/gene/10090:Rpl9 ^@ http://purl.uniprot.org/uniprot/P51410|||http://purl.uniprot.org/uniprot/Q5EBQ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL6 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Kcnab3 ^@ http://purl.uniprot.org/uniprot/Q8C439|||http://purl.uniprot.org/uniprot/Q8C7S9|||http://purl.uniprot.org/uniprot/Q8VD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the shaker potassium channel beta subunit family.|||Cytoplasm http://togogenome.org/gene/10090:Fsd1 ^@ http://purl.uniprot.org/uniprot/Q7TPM6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ B30.2 box contains a microtubule-binding site.|||Cleavage furrow|||Cytoplasm|||May be involved in microtubule organization and stabilization.|||Nucleus|||Oligomerization is required for binding to microtubules.|||centrosome http://togogenome.org/gene/10090:Pou3f3 ^@ http://purl.uniprot.org/uniprot/P31361 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the POU transcription factor family. Class-3 subfamily.|||Brain.|||Can fully replace Pou3f1 in Schwann cells of embryonic mice and rescue peripheral nervous system development in these animals, although severe defects in forebrain development are still observed.|||Expressed in the developing neocortex, both in the late precursor cells and in the migrating neurons.|||Homodimer.|||Neonatal death at least 36 hours postpartum. Loss of both Pou3f3 and Pou3f2 leads to abnormal formation of the neocortex with dramatically reduced production of layer IV-II neurons and defective migration of neurons.|||Nucleus|||Transcription factor that acts synergistically with SOX11 and SOX4 (By similarity). Plays a role in neuronal development. Is implicated in an enhancer activity at the embryonic met-mesencephalic junction; the enhancer element contains the octamer motif (5'-ATTTGCAT-3'). http://togogenome.org/gene/10090:Col5a3 ^@ http://purl.uniprot.org/uniprot/Q9JLI2 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Slc41a2 ^@ http://purl.uniprot.org/uniprot/B2RQZ3|||http://purl.uniprot.org/uniprot/Q8BYR8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a magnesium transporter.|||Acts as a plasma-membrane magnesium transporter (PubMed:15809054). Can also mediate the transport of other divalent metal cations in an order of Ba(2+) > Ni(2+) > Co(2+) > Fe(2+) > Mn(2+) (PubMed:15809054).|||Belongs to the SLC41A transporter family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gbp9 ^@ http://purl.uniprot.org/uniprot/Q8BTS3 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. http://togogenome.org/gene/10090:Atp6v1h ^@ http://purl.uniprot.org/uniprot/A0A0A6YX18|||http://purl.uniprot.org/uniprot/Q8BVE3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase H subunit family.|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Subunit H is essential for V-ATPase activity, but not for the assembly of the complex (By similarity). Involved in the endocytosis mediated by clathrin-coated pits, required for the formation of endosomes (By similarity).|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with AP2M1 (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Arrb2 ^@ http://purl.uniprot.org/uniprot/A0A158SIT9|||http://purl.uniprot.org/uniprot/J3JS97|||http://purl.uniprot.org/uniprot/Q91YI4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the arrestin family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes. During homologous desensitization, beta-arrestins bind to the GPRK-phosphorylated receptor and sterically preclude its coupling to the cognate G-protein; the binding appears to require additional receptor determinants exposed only in the active receptor conformation. The beta-arrestins target many receptors for internalization by acting as endocytic adapters (CLASPs, clathrin-associated sorting proteins) and recruiting the GPRCs to the adapter protein 2 complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the extent of beta-arrestin involvement appears to vary significantly depending on the receptor, agonist and cell type. Internalized arrestin-receptor complexes traffic to intracellular endosomes, where they remain uncoupled from G-proteins. Two different modes of arrestin-mediated internalization occur. Class A receptors, like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-arrestin at or near the plasma membrane and undergo rapid recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and TACR1 internalize as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptors, for extended periods of time. Receptor resensitization then requires that receptor-bound arrestin is removed so that the receptor can be dephosphorylated and returned to the plasma membrane. Mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and ATP-stimulated internalization of P2RY2. Involved in phosphorylation-dependent internalization of OPRD1 and subsequent recycling or degradation. Involved in ubiquitination of IGF1R. Beta-arrestins function as multivalent adapter proteins that can switch the GPCR from a G-protein signaling mode that transmits short-lived signals from the plasma membrane via small molecule second messengers and ion channels to a beta-arrestin signaling mode that transmits a distinct set of signals that are initiated as the receptor internalizes and transits the intracellular compartment. Acts as signaling scaffold for MAPK pathways such as MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by the beta-arrestin scaffold are largely excluded from the nucleus and confined to cytoplasmic locations such as endocytic vesicles, also called beta-arrestin signalosomes. Acts as signaling scaffold for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated signaling relies on both ARRB1 and ARRB2 (codependent regulation) include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-mediated signaling relies on either ARRB1 or ARRB2 and is inhibited by the other respective beta-arrestin form (reciprocal regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-mediated activation (reciprocal regulation). Involved in CCR7-mediated ERK1/2 signaling involving ligand CCL19. Is involved in type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10 activity. Is involved in dopamine-stimulated AKT1 activity in the striatum by disrupting the association of AKT1 with its negative regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to function as signaling scaffold involved in regulation of MIP-1-beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation of NF-kappa-B-dependent transcription in response to GPCR or cytokine stimulation by interacting with and stabilizing CHUK. Suppresses UV-induced NF-kappa-B-dependent activation by interacting with CHUK. The function is promoted by stimulation of ADRB2 and dephosphorylation of ARRB2. Involved in IL8-mediated granule release in neutrophils (By similarity). Involved in p53/TP53-mediated apoptosis by regulating MDM2 and reducing the MDM2-mediated degradation of p53/TP53. May serve as nuclear messenger for GPCRs. Upon stimulation of OR1D2, may be involved in regulation of gene expression during the early processes of fertilization. Also involved in regulation of receptors other than GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-regulates TGF-beta signaling such as NF-kappa-B activation. Involved in endocytosis of low-density lipoprotein receptor/LDLR. Involved in endocytosis of smoothened homolog/Smo, which also requires GRK2. Involved in endocytosis of SLC9A5. Involved in endocytosis of ENG and subsequent TGF-beta-mediated ERK activation and migration of epithelial cells. Involved in Toll-like receptor and IL-1 receptor signaling through the interaction with TRAF6 which prevents TRAF6 autoubiquitination and oligomerization required for activation of NF-kappa-B and JUN. Involved in insulin resistance by acting as insulin-induced signaling scaffold for SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1. Involved in the internalization of the atypical chemokine receptor ACKR3 (By similarity). Acts as an adapter protein coupling FFAR4 receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. During the activation step of NLRP3 inflammasome, directly associates with NLRP3 leading to inhibition of pro-inflammatory cytokine release and inhibition of inflammation.|||Homooligomer; the self-association is mediated by InsP6-binding (Probable). Heterooligomer with ARRB1; the association is mediated by InsP6-binding. Interacts with ADRB2 and CHRM2. Interacts with PDE4A. Interacts with PDE4D. Interacts with MAPK10, MAPK1 and MAPK3. Interacts with DRD2. Interacts with FSHR. Interacts with CLTC. Interacts with HTR2C. Interacts with CCR5. Interacts with CXCR4. Interacts with SRC. Interacts with DUSP16; the interaction is interrupted by stimulation of AGTR1 and activation of MAPK10. Interacts with CHUK; the interaction is enhanced stimulation of ADRB2. Interacts with RELA. Interacts with MDM2; the interaction is enhanced by activation of GPCRs. Interacts with SLC9A5. Interacts with TRAF6. Interacts with IGF1R. Interacts with ENG. Interacts with ARRB2. Interacts with KIR2DL1, KIR2DL3 and KIR2DL4. Interacts with LDLR. Interacts with AP2B1. Interacts with C5AR1. Interacts with RAF1. Interacts with MAP2K1. Interacts with MAPK1. Interacts with MAPK10; the interaction enhances MAPK10 activation by MAP3K5. Interacts with MAP2K4; the interaction is enhanced by presence of MAP3K5 and MAPK10. Interacts with MAP3K5. Interacts with AKT1. Interacts with IKBKB and MAP3K14. Interacts with SMO (activated). Interacts with GSK3A and GSK3B. Interacts with CXCR4; the interaction is dependent on C-terminal phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with GPR143. Interacts with HCK and CXCR1 (phosphorylated) (By similarity). Associates with protein phosphatase 2A (PP2A). Interacts with ACKR3 and ACKR4 (By similarity). Interacts with ARRDC1; the interaction is direct (By similarity). Interacts with GPR61, GPR62 and GPR135 (By similarity). Interacts (via NACHT and LRR domains) with NLRP3; this interaction is direct and inducible by omega-3 polyunsaturated fatty acids (PUFAs) (By similarity). Interacts with FFAR4 (via C-terminus); this interaction is stimulated by long-chain fatty acids (LCFAs) (PubMed:26873857).|||Hydroxylation by PHD2 modulates the rate of internalization by slowing down recruitment to the plasma membrane and inhibiting subsequent co-internalization with class A receptors.|||Loss of beta-2 adrenergic receptor/ADRB2 ubiquitination. Reduction of dopamine-dependent behaviors, loss of Akt1 regulation by dopamine in the striatum and disruption of the dopamine-dependent interaction of Akt1 with its negative regulator, protein phosphatase 2A. Increased serum LDL-cholesterol levels upon high fat diet. Exacerbates insulin resistance. Elevated cytotoxicity of natural killer cells and lowered susceptibility to mouse cytomegalovirus infection.|||Nucleus|||Phosphorylated at Thr-383 in the cytoplasm; probably dephosphorylated at the plasma membrane. The phosphorylation does not regulate internalization and recycling of ADRB2, interaction with clathrin or AP2B1 (By similarity).|||Predominantly localized in neuronal tissues and in the spleen.|||The ubiquitination status appears to regulate the formation and trafficking of beta-arrestin-GPCR complexes and signaling. Ubiquitination appears to occur GPCR-specific. Ubiquitinated by MDM2; the ubiquitination is required for rapid internalization of ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a dissociation of the beta-arrestin-GPCR complex. Stimulation of a class A GPCR, such as ADRB2, induces transient ubiquitination and subsequently promotes association with USP33. Stimulation of a class B GPCR promotes a sustained ubiquitination. Deubiquitinated by USP20; allowing USP20 to deubiquitinate TRAF6 leading to inhibition of NF-kappa-B signaling (By similarity).|||clathrin-coated pit http://togogenome.org/gene/10090:Hsd11b1 ^@ http://purl.uniprot.org/uniprot/P50172 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Controls the reversible conversion of biologically active glucocorticoids such as 11-dehydrocorticosterone to corticosterone in the presence of NADP(H) (PubMed:9405715, PubMed:23415904, PubMed:30902677). Participates in the corticosteroid receptor-mediated anti-inflammatory response, as well as metabolic and homeostatic processes (PubMed:9405715). Bidirectional in vitro, predominantly functions as a reductase in vivo, thereby increasing the concentration of active glucocorticoids (PubMed:23415904). It has broad substrate specificity, besides glucocorticoids, it accepts other steroid and sterol substrates (PubMed:23415904). Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-oxopregnenolone and 7beta-hydroxypregnenolone, 7-oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-17-one), among others (By similarity). Catalyzes the stereo-specific conversion of the major dietary oxysterol, 7-ketocholesterol (7-oxocholesterol), into the more polar 7-beta-hydroxycholesterol metabolite (PubMed:23415904). 7-oxocholesterol is one of the most important oxysterols, it participates in several events such as induction of apoptosis, accumulation in atherosclerotic lesions, lipid peroxidation, and induction of foam cell formation (By similarity). Mediates the 7-oxo reduction of 7-oxolithocholate mainly to chenodeoxycholate, and to a lesser extent to ursodeoxycholate, both in its free form and when conjugated to glycine or taurine, providing a link between glucocorticoid activation and bile acid metabolism (By similarity). Catalyzes the synthesis of 7-beta-25-dihydroxycholesterol from 7-oxo-25-hydroxycholesterol in vitro, which acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration (PubMed:30902677).|||Endoplasmic reticulum membrane|||Homodimer.|||In null mice, 11-keto corticosteroids cannot be reduced to active 11-hydroxy forms (PubMed:9405715). Plasma corticosterone levels actually are elevated at the diurnal nadir (PubMed:9405715). Males display adrenocortical hyperplasia (PubMed:9405715). During starvation, induction of hepatic glucose-6-phosphatase (G6Pase) mRNA and enzyme activity is lost and the induction of phosphoenolpyruvate carboxykinase (PEPCK) is attenuated (PubMed:9405715). Liver glycogen levels significantly increase in the fed state (PubMed:9405715). The liver shows a phenotype of partial glucocorticoid deficiency, despite somewhat increased basal plasma corticosterone levels (PubMed:9405715).|||Widely expressed. Highest levels (mRNA) in liver, kidney and lung, lower levels in the cerebellum, cortex, hippocampus, ovary, testis and thymus, no expression in colon. http://togogenome.org/gene/10090:Krt9 ^@ http://purl.uniprot.org/uniprot/Q6RHW0 ^@ Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in footpad epidermis and testis (at protein level).|||Heterotetramer of two type I and two type II keratins.|||May serve an important special function either in the mature palmar and plantar skin tissue or in the morphogenetic program of the formation of these tissues. Plays a role in keratin filament assembly (By similarity). Plays an essential role in the correct development of sperm.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Uqcc1 ^@ http://purl.uniprot.org/uniprot/Q9CWU6 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CBP3 family.|||Cytoplasmic vesicle|||Expressed mainly in the developing nervous system from 9.5 dpc onwards. Also detected in the developing eye and the brown fat.|||In the brain it is restricted to the olfactory bulb, the hippocampus, the piriform cortex and the Purkinje cells.|||Interacts with UQCC2 (By similarity). Interacts with UQCC3 (PubMed:35977508). Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508). Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508). Forms a complex, named COMA, composed of UQCC1, UQCC2 and UQCC4; activates MT-CYB translation (PubMed:35977508). Forms a complex, named COMC, composed of UQCC1, UQCC2; UQCC3 and UQCC4; mediates MT-CYB hemylation and association with the first nuclear-encoded CIII subunit UQCRQ (PubMed:35977508).|||Mitochondrion inner membrane|||Repressed by bFGF; in embryonic stem cells.|||Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex) (PubMed:35977508). Involved in cytochrome b translation and/or stability (PubMed:35977508). http://togogenome.org/gene/10090:Borcs8 ^@ http://purl.uniprot.org/uniprot/D3Z373|||http://purl.uniprot.org/uniprot/Q9D6Y4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.|||Belongs to the BORCS8 family.|||Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN.|||Lysosome membrane|||Membrane http://togogenome.org/gene/10090:Fbxo24 ^@ http://purl.uniprot.org/uniprot/Q9D417 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Efna5 ^@ http://purl.uniprot.org/uniprot/O08543 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Binds to the receptor tyrosine kinases EPHA2, EPHA3 and EPHB1. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function (By similarity). Binds to EPHB2. Interacts with EPHA8; activates EPHA8.|||Cell membrane|||Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion.|||Expressed in myogenic progenitor cells.|||In myogenic progenitor cells, highly expressed at 11.5 dpc and ceases its expression at the late fetal stage (17.5 dpc).|||Mice display cataract an opacification of the lens.|||caveola http://togogenome.org/gene/10090:Or52z13 ^@ http://purl.uniprot.org/uniprot/K7N6B3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rack1 ^@ http://purl.uniprot.org/uniprot/P68040 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.|||Cell membrane|||Cytoplasm|||Expressed throughout embryonic brain development with high levels detected at 11.5 dpc, 13.5 dpc and 18.5 dpc. Also detected at high levels in the adult brain.|||Monomer; also forms homodimers and homooligomers (By similarity). Interacts with CPNE3 (By similarity). May interact with ABCB4 (By similarity). Component of the small (40S) ribosomal subunit (PubMed:36517592). Interacts with LARP4B. Interacts with LARP4. Interacts with PKD2L1 (By similarity). Binds NHERF1 (By similarity). Forms a ternary complex with TRIM63 and PRKCE (By similarity). Interacts with HABP4, KRT1 and OTUB1 (By similarity). Interacts with SRC (via SH2 domain); the interaction is enhanced by tyrosine phosphorylation of RACK1 (By similarity). Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and PRKCA (PubMed:20093473). Interacts with AR (By similarity). Interacts with IGF1R but not with INSR (By similarity). Interacts with ADAM12 (By similarity). Interacts with CLEC1B (via N-terminal region) and with HIF1A; the interaction promotes their degradation (By similarity). Interacts with RHOA; this enhances RHOA activation and promotes cell migration (By similarity). Interacts with CHRM2; the interaction regulates CHRM2 internalization (By similarity). Interacts with TRPM6 (via kinase domain) (PubMed:18258429). Interacts with PTK2/FAK1; required for PTK2/FAK1 phosphorylation and dephosphorylation (By similarity). Interacts with FLT1 (By similarity). Interacts with HRAS (By similarity). Interacts with SLC9A5; this interaction regulates SLC9A5 cell-surface targeting and SLC9A5 activity (By similarity). Interacts with SLC9A6; this interaction regulates the distribution of SLC9A6 between endosomes and the plasma membrane (By similarity). Interacts with AIM2; promoting association with PP2A phosphatase and dephosphorylation of AKT1 (PubMed:33505023).|||Nucleus|||Perikaryon|||Phosphorylated on Tyr-228 and/or Tyr-246 by SRC. This is required for binding to SRC (By similarity).|||Scaffolding protein involved in the recruitment, assembly and/or regulation of a variety of signaling molecules (PubMed:7968370, PubMed:18258429, PubMed:20093473, PubMed:21262816, PubMed:33505023, PubMed:36517592). Interacts with a wide variety of proteins and plays a role in many cellular processes (PubMed:7968370, PubMed:18258429, PubMed:20093473, PubMed:21262816, PubMed:36517592). Component of the 40S ribosomal subunit involved in translational repression (PubMed:36517592). Involved in the initiation of the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, by promoting ubiquitination of a subset of 40S ribosomal subunits (By similarity). Binds to and stabilizes activated protein kinase C (PKC), increasing PKC-mediated phosphorylation (By similarity). May recruit activated PKC to the ribosome, leading to phosphorylation of EIF6 (By similarity). Inhibits the activity of SRC kinases including SRC, LCK and YES1 (By similarity). Inhibits cell growth by prolonging the G0/G1 phase of the cell cycle (By similarity). Enhances phosphorylation of BMAL1 by PRKCA and inhibits transcriptional activity of the BMAL1-CLOCK heterodimer (PubMed:20093473). Facilitates ligand-independent nuclear translocation of AR following PKC activation, represses AR transactivation activity and is required for phosphorylation of AR by SRC (By similarity). Modulates IGF1R-dependent integrin signaling and promotes cell spreading and contact with the extracellular matrix (By similarity). Involved in PKC-dependent translocation of ADAM12 to the cell membrane (By similarity). Promotes the ubiquitination and proteasome-mediated degradation of proteins such as CLEC1B and HIF1A (By similarity). Required for VANGL2 membrane localization, inhibits Wnt signaling, and regulates cellular polarization and oriented cell division during gastrulation (PubMed:21262816). Required for PTK2/FAK1 phosphorylation and dephosphorylation (By similarity). Regulates internalization of the muscarinic receptor CHRM2 (By similarity). Promotes apoptosis by increasing oligomerization of BAX and disrupting the interaction of BAX with the anti-apoptotic factor BCL2L (By similarity). Inhibits TRPM6 channel activity (PubMed:18258429). Regulates cell surface expression of some GPCRs such as TBXA2R (By similarity). Plays a role in regulation of FLT1-mediated cell migration (By similarity). Involved in the transport of ABCB4 from the Golgi to the apical bile canalicular membrane (By similarity). Acts as an adapter for the dephosphorylation and inactivation of AKT1 by promoting recruitment of PP2A phosphatase to AKT1 (PubMed:33505023).|||Strongly and ubiquitously expressed in the embryonic and early postnatal brain. At 11.5 dpc, expressed in a high-dorsal to low-ventral gradient throughout the brain. At 13.5 dpc, most abundant in the telecephalon. At 18.5 dpc, expressed most abundantly in layers 1-4 of the cortex, striatum, hippocampus, dentate gyrus, and specific thalamic nuclei. This expression decreases during postnatal development and is localized in the dentate gyrus, habenula, piriform cortex, paraventricular nucleus of the hypothalamus and supraoptic nucleus of the adult brain.|||The 7 WD repeats mediate protein-protein interactions with binding partners.|||dendrite|||perinuclear region http://togogenome.org/gene/10090:Chmp2a ^@ http://purl.uniprot.org/uniprot/Q9DB34 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF7 family.|||Cytoplasm|||ISGylated in a CHMP5-dependent manner. Isgylation weakens and inhibits its interactions with VPS4A and VTA1 respectively (By similarity).|||Late endosome membrane|||Nucleus envelope|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Recruited to the reforming nuclear envelope (NE) during anaphase by LEMD2 (By similarity). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4.|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. In vitro, heteromerizes with CHMP3 (but not CHMP4) to form helical tubular structures that expose membrane-interacting sites on the outside whereas VPS4B can associate on the inside of the tubule. Interacts with CHMP1B, CHMP2B, CHMP3, CHMP4A, CHMP4B, CHMP4C and CHMP5. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with MITD1. Interacts with VTA1; the interaction probably involves the open conformation of CHMP2A (By similarity).|||The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components.|||Widely expressed. Highly expressed in brain, heart, liver and kidney. http://togogenome.org/gene/10090:5430402E10Rik ^@ http://purl.uniprot.org/uniprot/Q9D3N5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Or4f4b ^@ http://purl.uniprot.org/uniprot/Q8VF49 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or3a1c ^@ http://purl.uniprot.org/uniprot/Q8VFX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rps26 ^@ http://purl.uniprot.org/uniprot/P62855|||http://purl.uniprot.org/uniprot/Q497N1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS26 family.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the small ribosomal subunit.|||Cytoplasm|||Rough endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Rgs18 ^@ http://purl.uniprot.org/uniprot/Q99PG4 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in bone marrow, spleen, fetal liver and lung. At very low levels expressed in heart.|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G(i) alpha-1, G(i) alpha-2, G(i) alpha-3 and G(q) alpha. http://togogenome.org/gene/10090:Xrcc1 ^@ http://purl.uniprot.org/uniprot/Q3TGI0|||http://purl.uniprot.org/uniprot/Q60596 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Embryonic lethal. Conditional knockout in brain causes cerebellar histopathology including increased apoptosis of cerebellar granule neurons, reduced numbers of cerebellar interneurons and decreased electrophysiological spike activity in Purkinje cells. Mutant mice exhibit cerebellar ataxia and elevated levels of ADP-ribose in cerebellum. Double knockout with PARP1 restores the normal interneuron density and ADP-ribose levels, reducing cerebellar ataxia in comparison to the single XRCC1 knockout mice.|||Homodimer. Interacts with polynucleotide kinase (PNK), DNA polymerase-beta (POLB) and DNA ligase III (LIG3). Interacts with APTX and APLF. Interacts with APEX1; the interaction is induced by SIRT1 and increases with the acetylated form of APEX1. Interacts with (poly-ADP-ribosylated) PARP1.|||Nucleus|||Phosphorylation of Ser-371 causes dimer dissociation. Phosphorylation by CK2 promotes interaction with APTX and APLF (By similarity).|||Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes (By similarity). Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity (PubMed:28002403). Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity (By similarity).|||Sumoylated. http://togogenome.org/gene/10090:Dbr1 ^@ http://purl.uniprot.org/uniprot/Q923B1 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Active in presence of diverse metals including Fe(2+), Zn(2+), Mn(2+) (By similarity). Also activated by Ca(2+) (By similarity). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (By similarity).|||Belongs to the lariat debranching enzyme family.|||Binds 2 divalent metal cations per subunit.|||Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover (PubMed:11355701). Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication and have an antiviral cell-intrinsic defense function (By similarity).|||Nucleus http://togogenome.org/gene/10090:Tmem170 ^@ http://purl.uniprot.org/uniprot/Q9D342 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a regulator of endoplasmic reticulum (ER) and nuclear envelope (NE) morphogenesis. Affects the ratio between tubular ER and ER sheets by promoting sheet formation at the expense of tubules. Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins.|||Belongs to the TMEM170 family.|||Endoplasmic reticulum membrane|||Interacts with RTN4.|||Nucleus envelope http://togogenome.org/gene/10090:Elfn1 ^@ http://purl.uniprot.org/uniprot/Q8C8T7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with PPP1CA.|||Membrane|||Postsynaptic protein that regulates circuit dynamics in the central nervous system by modulating the temporal dynamics of interneuron recruitment. Specifically present in excitatory synapses onto oriens-lacunosum molecular (OLM) interneurons and acts as a regulator of presynaptic release probability to direct the formation of highly facilitating pyramidal-OLM synapses. Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.|||Selectively expressed in perialvear somatostatin (Sst)-containing interneurons.|||dendrite http://togogenome.org/gene/10090:Rubcn ^@ http://purl.uniprot.org/uniprot/Q80U62 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex II (PI3KC3-C2) in which the core composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 is associated with UVRAG; in the complex interacts directly with PI3KC3 and UVRAG (PubMed:19270693). Interacts with Rab7 (RAB7A or RAB7B) (GTP-bound form); Rab7 and UVRAG compete for RUBCN binding; can interact simultaneously with Rab7 and the PI3K complex. Interacts with CYBA and CYBB; indicative for the association with the CYBA:CYBB NADPH oxidase heterodimer. Interacts with NOX4 and probably associates with the CYBA:NOX4 complex. Interacts with YWHAB and CARD9 in a competitive and stimulation-dependent manner; RUBCN exchanges interaction from YWHAB to CARD9 upon stimulation with beta-1,3-glucan (By similarity).|||Early endosome|||Inhibits PIK3C3 activity; under basal conditions negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy. Negatively regulates endosome maturation and degradative endocytic trafficking and impairs autophagosome maturation process (PubMed:19270693). Can sequester UVRAG from association with a class C Vps complex (possibly the HOPS complex) and negatively regulates Rab7 activation (By similarity).|||Involved in regulation of pathogen-specific host defense of activated macrophages. Following bacterial infection promotes NADH oxidase activity by association with CYBA thereby affecting TLR2 signaling and probably other TLR-NOX pathways. Stabilizes the CYBA:CYBB NADPH oxidase heterodimer, increases its association with TLR2 and its phagosome trafficking to induce antimicrobial burst of ROS and production of inflammatory cytokines. Following fungal or viral infection (implicating CLEC7A (dectin-1)-mediated myeloid cell activation or RIGI-dependent sensing of RNA viruses) negatively regulates pro-inflammatory cytokine production by association with CARD9 and sequestering it from signaling complexes (By similarity).|||Late endosome|||Lysosome http://togogenome.org/gene/10090:Sgcd ^@ http://purl.uniprot.org/uniprot/P82347|||http://purl.uniprot.org/uniprot/Q544D4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sarcoglycan beta/delta/gamma/zeta family.|||Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.|||Disulfide bonds are present.|||Interacts with FLNC (By similarity). Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans. Interacts with DAG1.|||Most strongly expressed in skeletal and heart muscle. Also detected in proliferating myoblasts.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Lef1 ^@ http://purl.uniprot.org/uniprot/P27782|||http://purl.uniprot.org/uniprot/Q3TYB0|||http://purl.uniprot.org/uniprot/Q8BGZ9|||http://purl.uniprot.org/uniprot/Q8C402 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCF/LEF family.|||Binds the armadillo repeat of CTNNB1 and forms a stable complex. Binds TLE1, ALYREF/THOC4, MDFI and MDFIC (By similarity). Interacts with NLK (By similarity). Interacts with EP300 and PIASG. Interacts with DAZAP2 (PubMed:19304756).|||Expressed in Vgamma1.1 and Vgamma2 gamma-delta T-cells, however not expressed in gamma-delta thymocytes fated for Il17a expression (at protein level) (PubMed:17218525, PubMed:23562159). Expressed in alpha-beta T-cell lineages (PubMed:17218525). Expressed in the thymus (PubMed:1827423). Found in distinct epithelial cell compartments of the skin and is abundant in the hair-producing progenitors of the follicle (PubMed:10498690).|||Expressed in the lower molar mesenchyme at 13.5 dpc and 14.5 dpc (PubMed:8898217). Expressed in the distal tooth bud epithelium and condensing tooth mesenchyme surrounding the tooth bud during the bud stage of mandibular molar tooth development at 13.5 dpc (PubMed:27713059). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (at protein level) (PubMed:29148101). Detected throughout the basal layer, in ectodermal placodes and the underlying dermal condensates in embryonic skin, and in epithelium and mesenchyme from early hair germs at 16.5 dpc (at protein level) (PubMed:10498690). At birth expression decreases in the basal level of the epidermis and increases in hair bulbs, in particular in matrix and precortex (PubMed:10498690). At day 6-9 expression is concentrated in follicle bulbs and in the hair shaft in a concentric ring of hair-keratin-expressing cells derived from the precortex (PubMed:10498690). Detected in dermal papilla throughout the hair cycle, and in a subset of cells emanating from the bulge to form the secondary hair germ (PubMed:10498690).|||Nucleus|||Phosphorylated at Thr-153 and/or Ser-164 by NLK (By similarity). Phosphorylation by NLK at these sites represses LEF1-mediated transcriptional activation of target genes of the canonical Wnt signaling pathway (By similarity).|||Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors.|||Transcription factor that binds DNA in a sequence-specific manner (By similarity). Participates in the Wnt signaling pathway (PubMed:11445543). Activates transcription of target genes in the presence of CTNNB1 and EP300 (PubMed:12446687). PIASG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (PubMed:11731474). TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1 (By similarity). Regulates T-cell receptor alpha enhancer function (By similarity). Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression (PubMed:23562159). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (PubMed:29148101). May play a role in hair cell differentiation and follicle morphogenesis (PubMed:11445543). http://togogenome.org/gene/10090:H2-T24 ^@ http://purl.uniprot.org/uniprot/F8VQG4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:H2-Aa ^@ http://purl.uniprot.org/uniprot/P14434 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Slc5a2 ^@ http://purl.uniprot.org/uniprot/Q923I7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Electrogenic Na(+)-coupled sugar simporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (By similarity). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (PubMed:20616166).|||Expressed in epithelial cells of early proximal tubules (at protein level).|||Forms a heterodimer with PDZK1IP1; this interaction enhances the transporter activity over a hundred-fold.|||Mutant mice develop glucosuria associated with increased food and fluid intake. http://togogenome.org/gene/10090:Lama4 ^@ http://purl.uniprot.org/uniprot/P97927 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Domain G is globular.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-4 is a subunit of laminin-8 (laminin-411), laminin-9 (laminin-421) and laminin-14 (laminin-423).|||Secreted|||Strongly expressed in peripheral nerves, cardiac muscle, fat, dermis, lung stroma, aortic endothelium, endocardium and endothelium of blood vessels in skin and brain.|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Tmtc2 ^@ http://purl.uniprot.org/uniprot/Q56A06 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMTC family.|||Endoplasmic reticulum|||Membrane|||Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3. http://togogenome.org/gene/10090:Mad1l1 ^@ http://purl.uniprot.org/uniprot/Q9WTX8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAD1 family.|||Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (By similarity). Forms a heterotetrameric complex with the closed conformation form of MAD2L1 (C-MAD2) at unattached kinetochores during prometaphase, recruits an open conformation of MAD2L1 (O-MAD2) and promotes the conversion of O-MAD2 to C-MAD2, which ensures mitotic checkpoint signaling (By similarity).|||Homodimer (By similarity). Dimerizes via its N- and C- terminal regions (By similarity). Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (By similarity). Interacts with the closed conformation form of MAD2L1 (C-MAD2) and open conformation form of MAD2L1 (O-MAD2) (By similarity). It is unclear whether MAD1L1 dimerization promotes the conversion of closed to open conformation of MAD2L1 (By similarity). Formation of a heterotetrameric core complex containing two molecules each of MAD1L1 and of MAD2L1 promotes binding of another molecule of MAD2L1 to each MAD2L1, resulting in a heterohexamer (By similarity). Perturbation of the original MAD1L1-MAD2L1 structure by the spindle checkpoint may decrease MAD2L1 affinity for MAD1L1 (By similarity). CDC20 can compete with MAD1L1 for MAD2L1 binding, until the attachment and/or tension dampen the checkpoint signal, preventing further release of MAD2L1 on to CDC20 (By similarity). Also able to interact with the BUB1/BUB3 complex (By similarity). Interacts with NEK2 (By similarity). Interacts with TTK (By similarity). Interacts with TPR; the interactions occurs in a microtubule-independent manner (By similarity). Interacts with IK (By similarity). Interacts with the viral Tax protein (By similarity). Interacts with PRAP1 (By similarity).|||Nucleus|||Nucleus envelope|||Phosphorylated; by BUB1. Become hyperphosphorylated in late S through M phases or after mitotic spindle damage.|||centrosome|||kinetochore|||spindle|||spindle pole http://togogenome.org/gene/10090:Dgkq ^@ http://purl.uniprot.org/uniprot/Q6P5E8 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphatidylserine.|||Belongs to the eukaryotic diacylglycerol kinase family.|||Cell membrane|||Cytoplasm|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:26748701). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:26748701). Within the adrenocorticotropic hormone signaling pathway, produces phosphatidic acid which in turn activates NR5A1 and subsequent steroidogenic gene transcription (By similarity). Also functions downstream of the nerve growth factor signaling pathway being specifically activated in the nucleus by the growth factor (By similarity). Through its diacylglycerol activity also regulates synaptic vesicle endocytosis (PubMed:26748701).|||Expression increases through development and peaks at postnatal day 14.|||Homozygous knockout mice display no overt phenotype with respect to body size, mating, and lifespan.|||Interacts with RHOA (constitutively activated, GTP-bound); the interaction inhibits DGKQ. Interacts with PRKCE. Interacts with PRKCH. Interacts with PLCB1. Interacts with NR5A1; the interaction requires both LXXLL motifs in DGKQ and is required for full phosphatidic acid-mediated activation of NR5A1.|||Nucleus|||Nucleus matrix|||Nucleus speckle|||Phosphorylated by PRKCE and PRKCH in vitro.|||Synapse|||The L-X-X-L-L repeats are both required for binding and phosphatidic acid-mediated activation of the nuclear receptor NR5A1.|||Widely expressed in all brain regions, including the cortex and hippocampus with a specific expression in neuronal cells (at protein level).|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Itgb5 ^@ http://purl.uniprot.org/uniprot/G5E8F8|||http://purl.uniprot.org/uniprot/O70309|||http://purl.uniprot.org/uniprot/Q6PE70 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin beta chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. Beta-5 (ITGB5) associates with alpha-V (ITGAV) (Probable). Interacts with MYO10 (By similarity). Interacts with DAB2. Integrin ITGAV:ITGB5 interacts with FBLN5 (via N-terminus) (PubMed:11805835). ITGAV:ITGB5 interacts with CCN3 (By similarity). Interacts with tensin TNS3; TNS3 also interacts with PEAK1, thus acting as an adapter molecule to bridge the association of PEAK1 with ITGB5 (By similarity).|||Integrin alpha-V/beta-5 (ITGAV:ITGB5) is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligand.|||Membrane|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site. http://togogenome.org/gene/10090:Tdpoz9 ^@ http://purl.uniprot.org/uniprot/P0DMR6 ^@ Similarity ^@ Belongs to the Tdpoz family. http://togogenome.org/gene/10090:Ube2e2 ^@ http://purl.uniprot.org/uniprot/Q91W82 ^@ Function|||PTM|||Similarity ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. Catalyzes the ISGylation of influenza A virus NS1 protein.|||Autoubiquitinated.|||Belongs to the ubiquitin-conjugating enzyme family. http://togogenome.org/gene/10090:Smurf1 ^@ http://purl.uniprot.org/uniprot/Q9CUN6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated in presence of NDFIP1. Ubiquitinated by the SCF(FBXL15) complex at Lys-355 and Lys-357, leading to its degradation by the proteasome. Lys-357 is the primary ubiquitination site.|||Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase that acts as a negative regulator of BMP signaling pathway (By similarity). Mediates ubiquitination and degradation of SMAD1 and SMAD5, 2 receptor-regulated SMADs specific for the BMP pathway (By similarity). Promotes ubiquitination and subsequent proteasomal degradation of TRAF family members and RHOA (By similarity). Promotes ubiquitination and subsequent proteasomal degradation of MAVS (PubMed:23087404). Acts as an antagonist of TGF-beta signaling by ubiquitinating TGFBR1 and targeting it for degradation (By similarity). Plays a role in dendrite formation by melanocytes (By similarity).|||Interacts with TRAF4 (By similarity). Interacts (via HECT domain) with FBXL15 (via LRR repeats) (By similarity). Interacts with SMAD7 and TGFBR1; SMAD7 recruits SMURF1 to TGFBR1 and regulates TGF-beta receptor degradation (By similarity). Interacts with MAVS; the interaction is mediated by NDFIP1 (PubMed:23087404).|||The C2 domain mediates membrane localization and substrate selection. http://togogenome.org/gene/10090:Prpsap1 ^@ http://purl.uniprot.org/uniprot/B1AT82|||http://purl.uniprot.org/uniprot/Q9D0M1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ribose-phosphate pyrophosphokinase family.|||Binds to PRPS1 and PRPS2.|||Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis. http://togogenome.org/gene/10090:H4c14 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Dusp16 ^@ http://purl.uniprot.org/uniprot/F6UIK0|||http://purl.uniprot.org/uniprot/Q6PCP3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Nucleus http://togogenome.org/gene/10090:Zc2hc1a ^@ http://purl.uniprot.org/uniprot/Q8BJH1 ^@ Similarity ^@ Belongs to the ZC2HC1 family. http://togogenome.org/gene/10090:Spdye4c ^@ http://purl.uniprot.org/uniprot/I6XKQ3 ^@ Similarity ^@ Belongs to the Speedy/Ringo family. http://togogenome.org/gene/10090:Trpm5 ^@ http://purl.uniprot.org/uniprot/Q9JJH7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM5 sub-subfamily.|||Cell membrane|||Mice show diminished behavioral and nerve responses to bitter, sweet and umami tastes.|||Phosphatidylinositol 4,5-bisphosphate (PIP2) is able to partially restore sensitivity to Ca(2+) after desensitization. Inhibited by flufenamic acid with an IC(50) of 24.5 uM and spermine with an IC(50) of 37 uM.|||Strongly expressed in liver, heart, testis, brain and kidney. Detected in fetal liver, kidney, spleen, brain, heart and lung, and in adult skin, eyes, spleen, stomach, small intestine, colon, lung, bladder, pancreas and thymus. Biallelically expressed at all stages and tissues examined. Also expressed in subsets of taste receptor cells of the tongue, in olfactory sensory neurons of the main olfactory epithelium and in the vomeronasal organ.|||Voltage-modulated Ca(2+)-activated, monovalent cation channel (VCAM) that mediates a transient membrane depolarization and plays a central role in taste transduction. Monovalent-specific, non-selective cation channel that mediates the transport of Na(+), K(+) and Cs(+) ions equally well. Activated directly by increases in intracellular Ca(2+), but is impermeable to it. Gating is voltage-dependent and displays rapid activation and deactivation kinetics upon channel stimulation even during sustained elevations in Ca(2+). Also activated by a fast intracellular Ca(2+) increase in response to inositol 1,4,5-triphosphate-producing receptor agonists. The channel is blocked by extracellular acidification. External acidification has 2 effects, a fast reversible block of the current and a slower irreversible enhancement of current inactivation. Is a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. Heat activation is due to a shift of the voltage-dependent activation curve to negative potentials. Activated by arachidonic acid in vitro. May be involved in perception of bitter, sweet and umami tastes. May also be involved in sensing semiochemicals. http://togogenome.org/gene/10090:Rbm39 ^@ http://purl.uniprot.org/uniprot/Q8VH51 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Interacts with NCOA6 and JUN (PubMed:11704680). Interacts with ESR1 and ESR2, in the presence of estradiol (E2) (PubMed:11704680). Interacts with RSRC1 (via Arg/Ser-rich domain) (By similarity). Interacts with SF3B1 (By similarity). Interacts with ZNF106 (via N-terminus) (PubMed:27418600).|||Nucleus|||RNA-binding protein that acts as a pre-mRNA splicing factor. Acts by promoting exon inclusion via regulation of exon cassette splicing (By similarity). Also acts as a transcriptional coactivator for steroid nuclear receptors ESR1/ER-alpha and ESR2/ER-beta, and JUN/AP-1, independently of the pre-mRNA splicing factor activity (PubMed:11704680). http://togogenome.org/gene/10090:Rnf39 ^@ http://purl.uniprot.org/uniprot/A2RT81 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm http://togogenome.org/gene/10090:Cass4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J199|||http://purl.uniprot.org/uniprot/Q08EC4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAS family.|||Docking protein that plays a role in tyrosine kinase-based signaling related to cell adhesion and cell spreading. Regulates PTK2/FAK1 activity, focal adhesion integrity, and cell spreading (By similarity).|||Interacts (via SH3 domain) with PTK2/FAK1 (via C-terminus).|||Phosphorylated on tyrosines by SRC.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Oosp1 ^@ http://purl.uniprot.org/uniprot/Q925U0 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PLAC1 family.|||Expressed in oocytes in primary through antral-stage follicles. Expressed in liver and ovary.|||Expressed in preimplantation embryo. Expressed in liver at 16 dpc but not at 13 dpc.|||May be involved in cell differentiation.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Secreted http://togogenome.org/gene/10090:Col4a3 ^@ http://purl.uniprot.org/uniprot/Q9QZS0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.|||Belongs to the type IV collagen family.|||Highly expressed in kidney and lung. Detected at lower levels in heart, muscle and skin.|||Mice exhibit normal pregnancy and wound healing, but consistent with the human hereditary disorder Alport syndrome they develop a progressive glomerulonephritis with microhematuria and proteinuria.|||Phosphorylated. Thought to be phosphorylated by CERT, but CERT does not have kinase activity.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.|||There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite promoter, respectively (PubMed:14633121). Interacts with ITGB3 (By similarity). Associates with LAMB2 at the neuromuscular junction and in GBM (PubMed:7962065).|||Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms.|||Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.|||Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.|||basement membrane http://togogenome.org/gene/10090:Got1 ^@ http://purl.uniprot.org/uniprot/P05201 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain.|||Cytoplasm|||Expressed in neurons of the retina. Localizes to the inner and outer plexiform layers, the inner and outer nuclear layer and the outer segments of photoreceptors.|||Homodimer.|||In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.|||Inhibited by calcium ions. http://togogenome.org/gene/10090:Grin2b ^@ http://purl.uniprot.org/uniprot/G3X9V4|||http://purl.uniprot.org/uniprot/Q01097 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B subfamily.|||Cell membrane|||Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:1377365, PubMed:26912815). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:1377365). In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (PubMed:20141836). Contributes to neural pattern formation in the developing brain (PubMed:8789948). Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (PubMed:8789948).|||Detected in brain (at protein level) (PubMed:8789948). Detected throughout the brain, and in brain stem trigeminal nucleus (PubMed:8789948). Detected in forebrain (PubMed:1377365).|||Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1377365, PubMed:26912815). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (PubMed:12008020, PubMed:14602821). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Found in a complex with GRIN1, GRIN3A and PPP2CB (By similarity). Found in a complex with GRIN1 and GRIN3B (PubMed:12008020, PubMed:14602821). Interacts with MAGI3 (By similarity). Interacts with HIP1 and NETO1 (PubMed:17329427, PubMed:19243221). Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with DAPK1 (PubMed:20141836). Found in a complex with GRIN1 and PRR7. Interacts with PRR7 (By similarity). Interacts with CAMK2A (By similarity). Interacts with ARC; preventing ARC oligomerization (By similarity). Interacts with TMEM25 (PubMed:31424425).|||Late endosome|||Lysosome|||Membrane|||Mutant pups are born at the expected Mendelian rate and appear grossly normal, but lack suckling behavior. As a consequence, all die shortly after birth, except when they are fed manually via a soft tube that delivers milk directly into the stomach. While mutant neonate brain structures are grossly normal, the mutant brain stem trigeminal complex lacks the neural repeating units called barrelettes that correspond to whisker-associated nerve fibers. Primary afferent nerve fibers from whiskers fail to show normal clustering in the region where barrelette structures form in wild-type. In contrast, nasolabial motor neurons appear normal. Contrary to wild-type neonates, brain slices from the mutant neonate hippocampus CA1 region lack NMDA receptor-type ion channel activity. Contrary to wild-type pups, prolonged low frequency stimulation of afferent fibers does not induce long-term depression (LTD) in the hippocampus.|||Phosphorylated on tyrosine residues (PubMed:12451687). Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity (PubMed:20141836).|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.|||Synaptic cell membrane|||cytoskeleton http://togogenome.org/gene/10090:Ascl5 ^@ http://purl.uniprot.org/uniprot/M0QWB7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in inner enamel epithelium (IEE) cells of molars at 14 dpc and 17 dpc, during ameloblast development (at protein level) (PubMed:30426815, PubMed:34812512). Expressed in molars and incisors at postnatal day 1 (P1) (at protein level) (PubMed:30426815). Expressed in Hertwig epithelial root sheath (HERS) cells during molar development (at protein level) (PubMed:30426815). Earliest expression in the incisor region at 11 dpc (PubMed:30426815).|||Expressed in teeth (at protein level).|||Interacts with transcription factor TCF3/E12.|||Knockout mice are fertile, but have enamel hypoplasia and small teeth (PubMed:30504223, PubMed:34812512). Abnormal ectopic expression of CDH1/E-cadherin in inner enamel epithelium (IEE) cells, but not in cells of the stratum intermedium (SI) at postnatal day 1 (P1) (PubMed:30504223). Inhibits the growth of clipped incisors (PubMed:30504223). Significantly reduces mRNA levels of SOX21, AMBN, ENAM, and AMELX in molars at P1 (PubMed:34812512). Develops fewer, smaller, incisors at 3 months of age in a transcription factor SP6/Epfn knockout background (PubMed:30504223). Epithelial cell invasion is inhibited and CDH1 ectopically expressed in dental epithelial cells at 3 months of age, in an SP6 knockout background (PubMed:30504223).|||Nucleus|||Transcription factor (PubMed:30426815). Probably binds E-box motifs 5'-CANNTG-3' in complex with transcription factor TCF3/E12 (PubMed:30426815). Negatively modulates transcription of target genes such as CDH1/E-cadherin, perhaps by recruiting the PRC2 repressive complex to regulatory elements (PubMed:30426815, PubMed:30504223). Regulates ameloblast development and tooth germ growth, perhaps acting by positively modulating migration of inner enamel epithelium (IEE) cells (PubMed:30426815, PubMed:30504223, PubMed:34812512). Plays a role in enamel formation (PubMed:34812512). http://togogenome.org/gene/10090:Ppm1j ^@ http://purl.uniprot.org/uniprot/Q149T7 ^@ Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PP2C family.|||Interacts with UBE2I/UBC9.|||Specifically expressed in the testicular germ cells. http://togogenome.org/gene/10090:Mettl23 ^@ http://purl.uniprot.org/uniprot/A2AA28 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily. METTL23 family.|||Cytoplasm|||Histone methyltransferase that dimethylates histone H3 at 'Arg-17', forming asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling (PubMed:28930672). Maternal factor involved in epigenetic chromatin reprogramming of the paternal genome in the zygote: mediates H3R17me2a, promoting histone H3.3 incorporation in the male pronucleus, leading to TET3 recruitment and subsequent DNA demethylation (PubMed:28930672).|||Interacts with HSPA5, HSP90B1, TUBULIN, UGGT1 and UGGT2 (By similarity). Interacts with TET3 (PubMed:28930672). Interacts with STPG4 (PubMed:28930672).|||Mice give birth to significantly smaller litter sizes (PubMed:28930672). Moreover, about a third of the homozygous newborn mice die before weaning and only a few survive to adulthood (PubMed:28930672). Strongly reduced 5-hydroxymethylcytosine (5hmC) levels in zygotes (PubMed:28930672).|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Aars2 ^@ http://purl.uniprot.org/uniprot/Q14CH7 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Binds 1 zinc ion per subunit.|||Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.|||Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Nup160 ^@ http://purl.uniprot.org/uniprot/Q9Z0W3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Functions as a component of the nuclear pore complex (NPC) (PubMed:11564755, PubMed:11684705). Involved in poly(A)+ RNA transport (PubMed:11684705).|||Part of the nuclear pore complex (NPC) (PubMed:11564755, PubMed:11684705). Forms part of the NUP160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and NUP96 (PubMed:11564755, PubMed:11684705). This complex plays a role in RNA export and in tethering NUP98 and NUP153 to the nucleus (PubMed:11564755, PubMed:11684705).|||nuclear pore complex http://togogenome.org/gene/10090:Stk16 ^@ http://purl.uniprot.org/uniprot/O88697 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Expressed at all stages of developing embryo.|||Mainly autophosphorylated on serine/threonine residues. Also autophosphorylated on Tyr-198 (By similarity).|||Membrane|||Membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. Also autophosphorylates (By similarity). May be involved in secretory vesicle trafficking or intracellular signaling. May have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. May be involved in TGF-beta signaling. Able to autophosphorylate on Tyr residue; it is however unclear whether it has tyrosine-protein kinase toward other proteins.|||Monomer. Interacts with DRG1 (via its N-terminal); the interaction phosphorylates DRG1.|||Ubiquitously expressed at low levels. Relatively higher levels in testis, kidney and liver.|||perinuclear region http://togogenome.org/gene/10090:Fem1a ^@ http://purl.uniprot.org/uniprot/Q9Z2G1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fem-1 family.|||Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1A (By similarity). Interacts with PTGER4 (PubMed:18270204). Interacts with NFKB1; the interaction is direct (PubMed:18270204).|||Cytoplasm|||Expressed during embryogenesis.|||Mitochondrion|||No visible phenotype in normal conditions: mice are fertile and develop normally without any apparent malformation (PubMed:26439841, PubMed:27315781). In mice model of chronic inflammation, mice develop more severe colitis induced by dextran sodium sulfate (DSS) (PubMed:26439841). Mice display less microglial accumulation; decreased microglial activation is observed in the brain after systemic lipopolysaccharide administration (PubMed:27315781). Mice also show behavioral abnormalities, possibly caused by monoamine deficits (PubMed:28336432). Mice display reduced anxiety-like behavior and brain inflammation in a model of Alzheimer disease (PubMed:28624505).|||Phosphorylated; highly phosphorylated in myoblasts and myotubes (PubMed:19406122). Phosphorylation at Ser-108 and Ser-608 promote PGE2-EP4-mediated inhibition of inflammation (PubMed:27799315). Dephosphorylated by protein phosphatase 2A (PP2A) (PubMed:27799315).|||Preferentially expressed in cardiac muscle, brain and liver (at protein level) (PubMed:9828124, PubMed:19406122). Also expressed in skeletal muscle (PubMed:9828124).|||Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (By similarity). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (By similarity). The CRL2(FEM1A) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2, leading to their ubiquitination and degradation (By similarity). Involved in PGE2-EP4-mediated inhibition of inflammation of macrophages via interaction with NFKB1 and PTGER4 (PubMed:18270204, PubMed:26439841). Promotes inflammation in brain microglia through MAP2K4/MKK4-mediated signaling (PubMed:27315781).|||Up-regulated in ischemic hearts. http://togogenome.org/gene/10090:Nos1 ^@ http://purl.uniprot.org/uniprot/Q9Z0J4 ^@ Activity Regulation|||Cofactor|||Disease Annotation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOS family.|||Binds 1 FAD.|||Binds 1 FMN.|||By cholinergic agonists acting at inositol phosphate-linked muscarinic receptors in cardiac myocytes.|||Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON (By similarity). Forms a ternary complex with CAPON and RASD1 (PubMed:11086993). Forms a ternary complex with CAPON and SYN1 (By similarity). Interacts with ZDHHC23 (By similarity). Interacts with NOSIP; which may impair its synaptic location (By similarity). Interacts with HTR4 (PubMed:15466885). Interacts with VAC14 (By similarity). Interacts (via N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ domains) (PubMed:10623522). Interacts with SLC6A4 (PubMed:17452640). Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway (PubMed:22081021). Interacts with DMD; localizes NOS1 to sarcolemma in muscle cells (PubMed:7545544). Interacts with DYNLL1; inhibits the nitric oxide synthase activity (By similarity).|||In MDX mice (mouse model of dystrophinopathy) the dystrophin complex is disrupted and nNOS is displaced from sarcolemma and accumulates in the cytosol.|||Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Isoform NNOS Mu may be an effector enzyme for the dystrophin complex.|||Stimulated by calcium/calmodulin. Inhibited by DYNLL1 that prevents the dimerization of the protein. Inhibited by NOSIP.|||Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.|||The PDZ domain participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes. Mediates interaction with VAC14.|||Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro).|||Widely expressed in the nervous system: expressed in cerebrum, olfactory bulb, hippocampus, midbrain, cerebellum, pons, medulla oblongata, and spinal cord. Also found in skeletal muscle, where it is localized beneath the sarcolemma of fast twitch muscle fibers, and in spleen, heart, kidney, and liver. N-NOS-1 and N-NOS-2 are found in all parts of the nervous system. NNOS beta and gamma occur in a region-specific manner in the brain and NNOS beta expression is developmentally regulated. NNOS Mu is only found in mature skeletal and cardiac muscles.|||dendritic spine|||sarcolemma http://togogenome.org/gene/10090:Muc5b ^@ http://purl.uniprot.org/uniprot/E9Q5I3|||http://purl.uniprot.org/uniprot/Q9CV93 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Agap2 ^@ http://purl.uniprot.org/uniprot/Q3UHD9 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Arf-GAP domain interacts with G domain and may regulate its GTPase activity.|||Belongs to the centaurin gamma-like family.|||Cytoplasm|||G domain binds GTP and has GTPase activity.|||GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid potentiates PIP2 stimulation (By similarity).|||GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. Aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase (By similarity).|||Interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2.|||Nucleus|||PH domain binds phospholipids and is required for nuclear targeting. http://togogenome.org/gene/10090:Crmp1 ^@ http://purl.uniprot.org/uniprot/P97427|||http://purl.uniprot.org/uniprot/Q6P1J1 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.|||Cytoplasm|||Expressed in DRG neurons of 12 dpc embryos.|||Homotetramer, and heterotetramer with DPYSL2, DPYSL3, DPYSL4 or DPYSL5 (PubMed:10956643, PubMed:14685275). Interacts with PLXNA1 (PubMed:14685275). Interacts with FLNA (via calponin-homology (CH) domain 1 and filamin repeat 24); the interaction alters FLNA ternary structure and thus promotes FLNA dissociation from F-actin (By similarity).|||Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.|||Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (PubMed:25358863, PubMed:14685275). Plays a role in axon guidance (PubMed:14685275). During the axon guidance process, acts downstream of SEMA3A to promote FLNA dissociation from F-actin which results in the rearrangement of the actin cytoskeleton and the collapse of the growth cone (PubMed:25358863). Involved in invasive growth and cell migration (By similarity). May participate in cytokinesis (By similarity).|||Perikaryon|||Phosphorylation at Ser-522 enhances CRMP1-mediated alteration of FLNA ternary structure and FLNA dissociation from F-actin.|||centrosome|||cytoskeleton|||growth cone|||spindle http://togogenome.org/gene/10090:Rec8 ^@ http://purl.uniprot.org/uniprot/Q8C5S7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rad21 family.|||Chromosome|||Expressed from 2 weeks postpartum (at protein level).|||Expressed primarily in the gonads. In the testis, expressed in pachytene spermatocytes and in spermatids. Not expressed in spermatogonia or somatic cells. In the ovary, expressed only in oocytes. Low levels also detected in a number of somatic tissues including thymus, lung, liver, kidney and small intestine.|||Interacts (phosphorylated and unphosphorylated form) with SMC3. Interacts with SYCP3. Interacts (phosphorylated and unphosphorylated form) with SMC1B. Does not interact with SMC1A. Interacts with RAD51. Forms a complex with EWSR1, PRDM9, SYCP3 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (PubMed:27932493).|||Mice display a high mortality rate, both during embryogenesis and after birth, germ cell failure and sterility. Mutant females exhibit ovarian dysgenesis and lack ovarian follicles at reproductive maturity. Affected males have small testes due to arrest of spermatogenesis during meiotic prophase I. Early chromosome pairing appears normal but synapsis occurs between sister chromatids rather than between homologous chromosomes.|||Nucleus|||Phosphorylated.|||Required during meiosis for separation of sister chromatids and homologous chromosomes. Proteolytic cleavage of REC8 on chromosome arms by separin during anaphase I allows for homologous chromosome separation in meiosis I and cleavage of REC8 on centromeres during anaphase II allows for sister chromatid separation in meiosis II.|||centromere http://togogenome.org/gene/10090:Septin12 ^@ http://purl.uniprot.org/uniprot/Q9D451 ^@ Similarity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family. http://togogenome.org/gene/10090:Slc12a4 ^@ http://purl.uniprot.org/uniprot/F8WIJ0|||http://purl.uniprot.org/uniprot/Q3TPD4|||http://purl.uniprot.org/uniprot/Q3TWZ6|||http://purl.uniprot.org/uniprot/Q3UDQ8|||http://purl.uniprot.org/uniprot/Q9JIS8 ^@ Activity Regulation|||Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by N-ethylmaleimide (NEM). Inhibited by DIOA.|||Belongs to the SLC12A transporter family.|||Cell membrane|||Detected in embryo, adult heart, erythrocytes, brain, kidney, stomach, ovary, testis and liver.|||Expression levels remained constant upon induction of erythroid differentiation of embryonic stem cells (PubMed:9516379). Not detected in reticulocytes, but present during differentiation of erythroleukemia cells to erythroblasts (PubMed:9516379).|||Homodimer (By similarity). Heteromultimer with other K-Cl cotransporters (PubMed:11551954).|||Inhibited by WNK3.|||Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10564083, PubMed:11551954). May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (Probable).|||Membrane|||Phosphorylated, phosphorylation may regulate transporter activity. http://togogenome.org/gene/10090:Ap2s1 ^@ http://purl.uniprot.org/uniprot/P62743|||http://purl.uniprot.org/uniprot/Q3UJ76 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with CCDC32; the interaction is direct and mediates association of CCDC32 with adaptor protein complex 2 (AP-2) (By similarity).|||Belongs to the adaptor complexes small subunit family.|||Cell membrane|||Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via Transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif. May also play a role in extracellular calcium homeostasis (By similarity).|||coated pit http://togogenome.org/gene/10090:Vmn2r79 ^@ http://purl.uniprot.org/uniprot/E9Q067 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Art3 ^@ http://purl.uniprot.org/uniprot/E9QNU1|||http://purl.uniprot.org/uniprot/Q8R2G4 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ 3'extension leads to out-of-frame translation.|||Belongs to the Arg-specific ADP-ribosyltransferase family.|||Cell membrane http://togogenome.org/gene/10090:Xpo1 ^@ http://purl.uniprot.org/uniprot/Q6P5F9|||http://purl.uniprot.org/uniprot/Q8BYY5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the exportin family.|||Cajal body|||Cytoplasm|||Found in a U snRNA export complex with PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA (PubMed:10786834). Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1. Found in a trimeric export complex with SNUPN, RAN and XPO1. Found in a nuclear export complex with RANBP3 and RAN. Found in a 60S ribosomal subunit export complex with NMD3, RAN, XPO1. Interacts with DDX3X, NMD3, NUP42, NUP88, NUP214, RANBP3 and TERT. Interacts with NEMF (via its N-terminus). Interacts with the monomeric form of BIRC5/survivin deacetylated at 'Lys-129'. Interacts with SERTAD2; the interaction translocates SERTAD2 out of the nucleus. Interacts with ATF2. Interacts with SLC35G1 and STIM1. Interacts with DCAF8 (By similarity). Interacts with DTNBP1 and the interaction translocates DTNBP1 out of the nucleus (PubMed:20921223). Interacts with CPEB3 (By similarity). Interacts with HAX1 (By similarity). Interacts with BOK; translocates to the cytoplasm (By similarity). Interacts with HSP90AB1 (By similarity). Interacts with LRPPRC; interacts with LRPPRC alone and also when LRPPRC is in complex with EIF4E and with EIF4E sensitivity element (4ESE)-containing mRNAs to form an EIF4E-dependent mRNA export complex (By similarity).|||Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase Ran in its active GTP-bound form. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Dnajc5b ^@ http://purl.uniprot.org/uniprot/Q9CQ94 ^@ PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with the chaperone complex consisting of HSC70 and SGTA.|||Membrane|||Palmitoylated. http://togogenome.org/gene/10090:Or4a67 ^@ http://purl.uniprot.org/uniprot/A2ATJ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Irag1 ^@ http://purl.uniprot.org/uniprot/Q9WUX5 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in smooth muscle such as aorta, colon and uterus. Detected in the brain, in the thalamus, in the hippocampus and myenteric plexus. Highly expressed in megakaryocytes. Down-regulated during macrophage differentiation.|||IRAG1 gene is a common integration site of murine leukemia virus, leading to induce myeloid leukemia in BXH2 mice. Murine leukemia virus integration occurs at the 5' end of the gene between 2 differentially used promoters and thus probably alters the expression of an important gene for myeloid cell growth.|||Membrane|||Mice lacking coiled-coil region N-terminal part exhibit disruption of IRAG1-ITPR1 interaction. They have dilated gastrointestinal tract and disturbed gastrointestinal motility. Smooth muscle are no more relaxed by cGMP after phenilephrine-induced contraction and half of the homozygous mice dies before the age of 6 months. Nitric oxide (NO) and cGMP-mediated inhibition of collagen-induced platelet aggregation is strongly suppressed in platelets of these transgenic mice. growth.|||Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1 (By similarity). Interacts with PRKG1/cGKI-beta and ITPR1/IP3R type I.|||Phosphorylated by PRKG1/cGKI.|||Plays a role as NO/PRKG1-dependent regulator of IP3-induced calcium release; its phosphorylation by PRKG1 inhibits bradykinin and IP3-induced calcium release from intracellular stores. Recruits PRKG1 to the endoplasmic reticulum and may mediate the assembly of PRKG1 and ITPR1 in a macrocomplex. Involved in PRKG1 signaling cascade leading to inhibition of platelet activation and aggregation. Mediates also NO-dependent inhibition of calcium signaling in gastrointestinal smooth muscle contributing to NO-dependent relaxation.|||Sarcoplasmic reticulum|||perinuclear region http://togogenome.org/gene/10090:4931408C20Rik ^@ http://purl.uniprot.org/uniprot/E9PWP9|||http://purl.uniprot.org/uniprot/Q3V0G6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Met ^@ http://purl.uniprot.org/uniprot/A4FUV6|||http://purl.uniprot.org/uniprot/F8VQL0 ^@ Caution|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Kcnq1 ^@ http://purl.uniprot.org/uniprot/P97414 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Deubiquitinated by USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores the membrane localization.|||Early endosome|||Endoplasmic reticulum|||Expressed in heart, kidney and salivary glands. Detected in the cochlea. Almost undetectable in brain, skeletal muscle and liver. Widely expressed in embryonic and neonatal tissues (PubMed:9618174). Expressed in choroid plexus epithelium (at protein level) (PubMed:24595108).|||Membrane raft|||Mice lacking Kcnq1 show an intestinal absorption impairment which is associated with reduced serum vitamin B12 concentrations, mild macrocytic anemia, and fecal loss of sodium and potassium ions (PubMed:16314573). Mice lacking Kcnq1 show microvillar secretory membranes intact, but basal acid secretion is absent and forskolin-stimulated acid output is reduced by approximately 90% in gastric mucosa (PubMed:19491250). Homozygous Kcnq1 mice develop normally and are viable, demonstrate hyperactivity, circling, and nodding behaviors; exhibit no electrocardiographic abnormalities but present a complete deafness, as well as circular movement and repetitive falling; show severe anatomic disruption of the cochlear and vestibular end organs; also display threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia (PubMed:11120752). Mice neonates lacking Kcnq1 display significantly prolonged QT intervals during baseline ECG assessments which significantly increased following isoproterenol challenge; furthermore, the slow delayed rectifier potassium current (IKs) is absent (PubMed:15004216).|||Phosphorylation at Ser-27 by PKA; increases delayed rectifier potassium channel activity of the KCNQ1-KCNE1 complex through a macromolecular complex that includes PKA, PP1, and the targeting protein AKAP9.|||Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (By similarity) (PubMed:16314573, PubMed:11120752, PubMed:15004216). Associates with KCNE beta subunits that modulates current kinetics (By similarity) (PubMed:17597584, PubMed:15004216). Induces a voltage-dependent by rapidly activating and slowly deactivating potassium-selective outward current (By similarity) (PubMed:8900282). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:15004216, PubMed:17597584). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (By similarity). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (By similarity). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (PubMed:16314573). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (PubMed:19491250). When associated with KCNE2, forms an heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (By similarity). When associated with KCNE4, inhibits voltage-gated potassium channel activity (By similarity). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (By similarity). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (By similarity). Binds with phosphatidylinositol 4,5-bisphosphate (By similarity). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability.|||Tetramer (By similarity). Heterotetramer with KCNE1; form the native cardiac channel I(Ks) which increases the amplitude and slows down the activation kinetics of outward potassium current and targets to the membrane raft (By similarity) (PubMed:8900282). Interacts (via C-terminus) with CALM; forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner. Interacts with AKAP9; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1) to the KCNQ1-KCNE1 complex, allowing PKA-mediated phosphorylation and increase of delayed rectifier potassium channel activity. Interacts with KCNE2; form an heterooligomer complex that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current. Interacts with AP2M1; mediates estrogen-induced internalization via clathrin-coated vesicles. Interacts with NEDD4L; promotes internalization and decreases I(Ks) currents. Interacts with USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization. Heterotetramer with KCNQ5; has a voltage-gated potassium channel activity. Interacts with KCNE3; alters membrane raft localization. Interacts with KCNE4; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity. Interacts with KCNE5; impairs KCNQ1 localization in lipid rafts and only conducts current upon strong and continued depolarization (By similarity). Interacts with SLC5A3; forms coregulatory channel-transporter complexes that modulate Na(+)-coupled myo-inositol influx through the transporter.|||The C-terminal assembly domain promotes self-interactiona; allows functional channel.|||The C-terminal coiled-coil domain interacts with a single CALM molecule via the first two membrane-proximal helical regions, with CALM forming a clamp-like structure. Binding of CALM C-terminus to the first helical region is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to the second helical region is calcium-dependent and regulates electrophysiological activity of the channel.|||The coiled-coil domain mediates tetramerization.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.|||The segment S6 is involved in the inhibition of voltage-gated potassium channel activity by KCNE4.|||Ubiquitinated by NEDD4L; promotes internalization. The ubiquitinylated form is internalized through a clathrin-mediated endocytosis by interacting with AP2M1 and is recycled back to the cell membrane via RAB4A and RAB11A. http://togogenome.org/gene/10090:Crtc3 ^@ http://purl.uniprot.org/uniprot/Q91X84 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TORC family.|||Binding, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1 enhances recruitment of TAF4 to the promoter (By similarity). 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction (By similarity). Interacts (when phosphorylated at Ser-162 and Se-273) with 14-3-3 proteins (PubMed:28235073, PubMed:30611118). Interacts with YWHAE (PubMed:30611118). Interacts (when phosphorylated at Ser-391) with phosphatase PP2A catalytic subunit PPP2CA and regulatory subunits PPP2R1A and PPP2R2A (PubMed:30611118).|||Cytoplasm|||Expressed in brown adipose tissues.|||Nucleus|||Phosphorylation/dephosphorylation states of Ser-273 are required for regulating transduction of CREB activity (PubMed:29211348). CRTCs/TORCs are inactive when phosphorylated, and active when dephosphorylated at this site (PubMed:29211348). May be phosphorylated at Ser-391 by MAPK3/ERK1 and/or MAPK1/ERK2 or by some cyclin-dependent kinases such as CDK1,CDK2 or CDK5 (PubMed:30611118). Following adenylyl cyclase activation, dephosphorylated at Ser-162 and Ser-273 resulting in its dissociation from 14-3-3 proteins probably promoting CRTC3 translocation into the nucleus (PubMed:30611118).|||Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites (PubMed:29211348, PubMed:30611118). Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated (PubMed:29211348). Acts independently of CREB1 'Ser-133' phosphorylation (By similarity). Enhances the interaction of CREB1 with TAF4 (By similarity). Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR (By similarity). Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells (By similarity). http://togogenome.org/gene/10090:Kansl2 ^@ http://purl.uniprot.org/uniprot/Q8BQR4 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.|||Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus http://togogenome.org/gene/10090:Fam166a ^@ http://purl.uniprot.org/uniprot/Q9D4K5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CIMIP2 family.|||Probable microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme.|||flagellum axoneme http://togogenome.org/gene/10090:Emc7 ^@ http://purl.uniprot.org/uniprot/Q14C26|||http://purl.uniprot.org/uniprot/Q9EP72 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC7 family.|||Component of the ER membrane protein complex (EMC).|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Cyp2ab1 ^@ http://purl.uniprot.org/uniprot/B9EHK4|||http://purl.uniprot.org/uniprot/E9PZ31|||http://purl.uniprot.org/uniprot/Q8BTM0 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Pi4k2a ^@ http://purl.uniprot.org/uniprot/Q2TBE6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the BLOC-1 and the AP-3 complexes; the BLOC-1 complex is required for optimal binding of PI4K2A to the AP-3 complex (PubMed:21998198). Interacts with BLOC1S5 and DTNBP1 (By similarity). Interacts with ITCH (PubMed:23146885). Interacts with FOS; this interaction may enhance phosphatidylinositol phosphorylation activity (PubMed:22105363). Interacts with ATG9A (By similarity).|||Belongs to the PI3/PI4-kinase family. Type II PI4K subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Detected in brain (at protein level).|||Endosome|||Membrane|||Membrane raft|||Membrane-bound phosphatidylinositol-4 kinase (PI4-kinase) that catalyzes the phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important roles in endocytosis, Golgi function, protein sorting and membrane trafficking and is required for prolonged survival of neurons. Besides, phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P) is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3).|||Mice are born at the expected Mendelian rate. Young animals have no visible phenotype, but oldeer mice develop urinary incontinence, head tremor, spastic gait, weakness of the hind limbs, followed by additional weakness of the forelimbs, weight loss and premature death. Their brains show no gross anatomical defects, but show loss of Purkinje cells. In addition, mice present massive axon degeneration in the ascending and descending tract of the spinal cord. Male mice are infertile and females are subfertile.|||Mitochondrion|||Palmitoylated by ZDHHC3 and ZDHHC7 in the CCPCC motif. Palmitoylation is cholesterol-dependent, and required for TGN localization (By similarity).|||Perikaryon|||Presynaptic cell membrane|||Ubiquitinated by ITCH; this does not lead to proteasomal degradation.|||dendrite|||neuron projection|||synaptosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Avil ^@ http://purl.uniprot.org/uniprot/O88398|||http://purl.uniprot.org/uniprot/Q3TBC5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates (via C-terminus) with actin (By similarity). Interacts with F-actin (By similarity). Interacts with SCARF1; the interaction occurs in embryonic dorsal root ganglions at 18 dpc and induces neurite-like outgrowth (PubMed:15247299). Interacts with PLCE1. Interacts with ACTR2 and ACTR3; associates with the ARP2/3 complex (By similarity).|||Belongs to the villin/gelsolin family.|||Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling. May have a unique function in the morphogenesis of neuronal cells which form ganglia. Required for SREC1-mediated regulation of neurite-like outgrowth. Plays a role in regenerative sensory axon outgrowth and remodeling processes after peripheral injury in neonates. Involved in the formation of long fine actin-containing filopodia-like structures in fibroblast. Plays a role in ciliogenesis (PubMed:15247299, PubMed:18160648). In podocytes, controls lamellipodia formation through the regulation of EGF-induced diacylglycerol generation by PLCE1 and ARP2/3 complex assembly (By similarity).|||Expressed almost exclusively in peripheral sensory neurons (craniofacial and dorsal root ganglia (DRG) sensory neurons), but also in trigeminal ganglia (TG) Me5 proprioceptive neurons and Mo5 motoneurons.|||Half of the homozygous mice die during embryogenesis, the other 50% do not show any noticeable abnormality in development, growth or behavior and are fertile.|||Most highly expressed in the endometrium of the uterus, the intestinal villi and the testes. Weaker expression also detected in the brain, dorsal root ganglions and on the surface of the tongue.|||axon|||cytoskeleton|||focal adhesion|||lamellipodium|||neuron projection http://togogenome.org/gene/10090:Resp18 ^@ http://purl.uniprot.org/uniprot/P47939 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RESP18 family.|||Endoplasmic reticulum|||Golgi apparatus|||May play an important regulatory role in corticotrophs.|||Pituitary, hypothalamus and pancreas. Highest levels are found in somatotrophes, mammotrophes, and gonadotrophes, and lower levels are found in corticotrophs and thyrotropes.|||Up-regulated by high levels of glucose.|||secretory vesicle lumen http://togogenome.org/gene/10090:Dmd ^@ http://purl.uniprot.org/uniprot/P11531 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission.|||Detected in quadriceps muscle and in sciatic nerve (at protein level) (PubMed:11430802). Differentially expressed during skeletal muscle, heart, and brain development. Also expressed in retina (PubMed:7633443).|||Interacts with SYNM (PubMed:16777071). Interacts with the syntrophins SNTG1 and SNTG2. Interacts with KRT19. Component of the dystrophin-associated glycoprotein complex which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts with DAG1 (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif of DAG1 (By similarity). Interacts with SYNM; SNTA1 and SNTB1. Interacts with CMYA5 (PubMed:20634290). Directly interacts with ANK2 and ANK3; these interactions do not interfere with betaDAG1-binding and are necessary for proper localization in muscle cells (PubMed:19109891). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (PubMed:11430802). Interacts with DTNB (PubMed:10893187). Interacts with PGM5; the interaction is direct (PubMed:7890770). Interacts with NOS1; localizes NOS1 to sarcolemma in muscle cells (PubMed:7545544).|||Mutant mice show reduced contractile force compared to wild-types, at least for soleus muscle. They have decreased motor activity levels after exercise, increased muscle permeability and fibrosis with impaired regeneration (PubMed:28498977). MEGF10 and DMD double knockout animals have pronounced fiber size variability and intracellular inclusions in the quadriceps femoris with extensive endomysial connective tissue infiltration. Mice develop muscle weakness, kyphosis and a waddling gait. At 2 months of age, they have reduced contractile force compared to wild-type mice. They display reduced motor activity after exercise and they walk shorter distances than wild-type. They have a delayed regeneration after muscle injury and an aberrant muscle fiber typing and cross-sectional areas (PubMed:28498977).|||Postsynaptic cell membrane|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Vmn1r28 ^@ http://purl.uniprot.org/uniprot/Q8R2C9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc22a5 ^@ http://purl.uniprot.org/uniprot/Q5SX17|||http://purl.uniprot.org/uniprot/Q9Z0E8 ^@ Activity Regulation|||Disease Annotation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basal cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Defects in Slc22a5 are the cause of the juvenile visceral steatosis (JVS) phenotype. JVS is an autosomal recessive animal model of systemic carnitine deficiency.|||Inhibited by emetine, quinidine and verapamil. The IC(50) of emetine is 4.2 uM. Not inhibited by valproic acid. Transport of (R)-carnitine is stimulated by cholesterol in the plasma membrane.|||Interacts with PDZK1.|||Intestinal expression is induced by IFNG.|||Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:20722056). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity).|||Widely expressed. Expressed in kidney, liver and testis (PubMed:11010964). Expressed at the brush border of the small, large intestine and colon (at protein level) (PubMed:11010964, PubMed:20722056). http://togogenome.org/gene/10090:Gfra2 ^@ http://purl.uniprot.org/uniprot/O08842|||http://purl.uniprot.org/uniprot/Q3UET6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GDNFR family.|||Cell membrane|||Expressed at low level in the ventral mesencephalon at 14 dpc. Highly expressed in the developing dorsal root ganglia (PubMed:9182803). Isoform 1, isoform 2 and isoform 3 are all highly expressed in the late embryonic development (15 dpc and 17 dpc) (PubMed:12829325).|||Interacts with SORL1.|||Neurons of the superior cervical and dorsal root ganglia, and adult brain and testis. Low level in the substantia nigra, spleen and adrenal gland (PubMed:9182803). Isoform 1, isoform 2 and isoform 3 are all expressed in brain, liver, ileum, spleen, heart and kidney (PubMed:9875703). In brain, isoform 1 is most abundant, isoform 2 slightly less and isoform 3 is lowest. No significant levels of isoform 1, isoform 2 or isoform 3 expression in testis (PubMed:12829325).|||Participates in NRTN-induced 'Ser-727' phosphorylation of STAT3.|||Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor. http://togogenome.org/gene/10090:Cngb3 ^@ http://purl.uniprot.org/uniprot/Q9JJZ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGB3 subfamily.|||Membrane|||Small subset of retinal photoreceptor cells and testis.|||Tetramer formed of three CNGA3 and one CNGB3 modulatory subunits.|||Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cGMP which leads to an opening of the cation channel and thereby causing a depolarization of rod photoreceptors. Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones (By similarity). Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGA3. http://togogenome.org/gene/10090:Sec61a2 ^@ http://purl.uniprot.org/uniprot/Q9JLR1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SecY/SEC61-alpha family.|||Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides.|||Endoplasmic reticulum membrane|||The SEC61 channel-forming translocon complex consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63. http://togogenome.org/gene/10090:Insl6 ^@ http://purl.uniprot.org/uniprot/Q545M1|||http://purl.uniprot.org/uniprot/Q9QY05 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the insulin family.|||May have a role in sperm development and fertilization.|||Secreted http://togogenome.org/gene/10090:Creg2 ^@ http://purl.uniprot.org/uniprot/Q8BGC9 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CREG family.|||Brain specific.|||Secreted http://togogenome.org/gene/10090:Gm17660 ^@ http://purl.uniprot.org/uniprot/B9UIU9 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in enamel organ.|||Secreted|||Tooth-associated epithelia protein that may participate in structuring the basal lamina at cell-tooth interface. http://togogenome.org/gene/10090:Atl3 ^@ http://purl.uniprot.org/uniprot/E9PYT3|||http://purl.uniprot.org/uniprot/Q91YH5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Endoplasmic reticulum membrane|||Expressed in cardiomyocytes (at protein level).|||GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (By similarity).|||Interacts with ZFYVE27 (By similarity). Interacts with REEP5 (PubMed:32075961). http://togogenome.org/gene/10090:Or10g1 ^@ http://purl.uniprot.org/uniprot/E9PZZ6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Hpn ^@ http://purl.uniprot.org/uniprot/O35453 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the peptidase S1 family.|||Cell membrane|||Detected in kidney, in thick ascending tubule epithelial cells (at protein level) (PubMed:26673890). Detected in kidney and liver (PubMed:9395459, PubMed:9435303).|||Major isoform.|||Minor isoform.|||No visible phenotype. Mice are viable and fertile (PubMed:9435303, PubMed:11127869). They present no defect in blood coagulation (PubMed:9435303). Likewise, they present no defect in liver regeneration after liver resection (PubMed:11127869). Mice have severely impaired hearing, with abnormal morphology of the tectorial membrane in the cochlea, but no visible defects of the organ of Corti and no loss of inner or outer hair cells. Mutant mice have reduced levels of thyroid hormone. This may play a role in their hearing deficit, since adequate levels of thyroid hormone are required for normal development of the auditory system (PubMed:17620368). Urine from mutant mice lacks normally processed Umod; contrary to wild-type, urinary Umod from mutant mice does not polymerize into long fibers (PubMed:26673890).|||Secreted|||Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL. Plays a role in cell growth and maintenance of cell morphology. Plays a role in the proteolytic processing of ACE2 (By similarity). Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890). http://togogenome.org/gene/10090:Npepps ^@ http://purl.uniprot.org/uniprot/Q11011 ^@ Activity Regulation|||Caution|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins.|||Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||It is uncertain whether Met-1 or Met-46 is the initiator.|||Mice exhibit dwarfism, increased anxiety, impaired pain responses and do not reproduce as well as wild-type mice. More MHC class I molecules are displayed on dendritic cell surfaces.|||Monomer.|||Nucleus|||Strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn(2+), Cd(2+), Co(2+), Cu(2+), Hg(2+), EDTA and puromycin. Not inhibited by PMSF, and only slightly inhibited by leupeptin and aprotinin. Activity is increased by Mg(2+) and Ca(2+) (By similarity).|||Widely expressed. Highest expression in brain, particularly the striatum and hippocampus. Expressed in Sertoli cells.|||cytosol http://togogenome.org/gene/10090:Rasgrf2 ^@ http://purl.uniprot.org/uniprot/P70392 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in brain in the nucleus of the solitary tract. Not observed in the hippocampus (at protein level).|||Expression increases in the cortex from birth to adulthood.|||Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation.|||Homooligomer and heterooligomer with RASGRF1. Interacts with Ras and RAC1. Interacts in a calcium-dependent manner with calmodulin. Interacts with EPB49 and probably CDK5R1. Interacts with the AMPA receptor through GRIA1. Interacts with microtubules.|||Mice do not display overt phenotype.|||Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1 activation.|||Preferentially activates HRAS in vivo compared to R-RAS based on their different types of prenylation.|||The DH (DBL-homology) domain mediates interaction with RASGRF1 and probably EPB49 and is required for RAC1 activation.|||The IQ domain mediates the calcium-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity.|||The Ras-GEF domain and the N-terminal Ras-GEF domain form a Ras-binding site and mediate Ras activation.|||Ubiquitinated upon interaction with Ras. Ubiquitination leads to degradation through the 26S proteasome. http://togogenome.org/gene/10090:Zfp966 ^@ http://purl.uniprot.org/uniprot/A2ART1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Flt4 ^@ http://purl.uniprot.org/uniprot/P35917|||http://purl.uniprot.org/uniprot/Q5SU94 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation in response to H(2)O(2) is mediated by a process that requires SRC and PRKCD activity. Phosphorylation at Tyr-1068 is required for autophosphorylation at additional tyrosine residues. Phosphorylation at Tyr-1063 and Tyr-1337 is important for interaction with CRK and subsequent activation of MAPK8. Phosphorylation at Tyr-1230, Tyr-1231 and Tyr-1337 is important for interaction with GRB2 and subsequent activation of the AKT1 and MAPK1/ERK2 and/or MAPK3/ERK1 signaling pathways. In response to endothelial cell adhesion onto collagen, can also be phosphorylated in the absence of FLT4 kinase activity by SRC (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell membrane|||Cytoplasm|||Embryonic lethality at about 13 dpc, due to failure of remodeling of the yolk sac capillary network and defects in remodeling and maturation of primary vascular networks.|||Expressed in adult lung and liver, and in fetal liver, brain, intestine and placenta.|||Interacts with VEGFC and VEGFD. Monomer in the absence of bound VEGFC or VEGFD. Homodimer in the presence of bound VEGFC or VEGFD. Can also form a heterodimer with KDR. Interacts with PTPN14; the interaction is enhanced by stimulation with VEGFC. Interacts with CRK, GRB2, PTK2/FAK1, SHC1, PIK3R1 and PTPN11/SHP-2. Identified in a complex with SRC and ITGB1 (By similarity).|||Membrane|||Nucleus|||Present in an inactive conformation in the absence of bound ligand. Binding of VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).|||The first and second Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding. The fourth and fifth Ig-like C2-type (immunoglobulin-like) domains are sufficient for homodimerization. The fifth and seventh Ig-like C2-type (immunoglobulin-like) domains are required for autophosphorylation and further activation.|||Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. http://togogenome.org/gene/10090:Lrguk ^@ http://purl.uniprot.org/uniprot/Q9D5S7 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detectable at low levels from birth, up-regulated at day 14 coincident with the appearance of pachytene spermatocytes, then maximal from day 18 coincident with the appearance of haploid germ cells (PubMed:25781171).|||Highly expressed in the testis (PubMed:25781171). During spermatid development is initially localized to a supra-nuclear region of round spermatids, and is particularly evident at the leading edge of the developing acrosome and acroplaxome. As maturation proceeded and nuclear elongation initiated, LRGUK moves distally to ultimately reside on the microtubules of the manchette. LRGUK is also evident in the sperm basal body and the sperm tail (PubMed:25781171).|||Interacts (via guanylate kinase-like domain) with RIMBP3 (via coiled-coil region) (PubMed:28003339). Interacts (via guanylate kinase-like domain) with HOOK2 (PubMed:25781171, PubMed:28003339). Interacts (via LRRCT domain) with KLC3. Interacts with HOOK1 and HOOK3 (PubMed:28003339).|||Involved in multiple aspects of sperm assembly including acrosome attachment, shaping of the sperm head and in the early aspects of axoneme development (PubMed:25781171). Not essential for primary cilium biogenesis (PubMed:28003339).|||Mutagenesis with N-ethyl-N-nitrosourea (ENU) lead to the discovery of the Kaos phenotype. The Kaos mutation results in the conversion of Arg-528 to a stop codon. Homozygous males are oligoasthenoteratospermic and sterile.|||acrosome|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Otulinl ^@ http://purl.uniprot.org/uniprot/A0A2I3BPS6|||http://purl.uniprot.org/uniprot/Q3TVP5 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although highly similar to the deubiquitinase OTULIN, lacks the conserved active site Cys at position 136 which is replaced by an Asp residue, and does not show deubiquitinase activity.|||Belongs to the peptidase C65 family. Otulin subfamily.|||Cytoplasm|||Does not bind ubiquitin or ubiquitin-like proteins.|||Endoplasmic reticulum membrane|||Lacks deubiquitinase activity.|||Nucleus envelope|||The N-terminal region that precedes the OTU domain mediates interaction with cellular membranes. http://togogenome.org/gene/10090:Copb2 ^@ http://purl.uniprot.org/uniprot/O55029 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat COPB2 family.|||COPI-coated vesicle membrane|||Golgi apparatus membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits. Probably interacts with PEX11A. Interacts with SCYL1. Interacts with JAGN1 (By similarity).|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity).|||The knockout of the gene results in early embryonic lethality with no viable embryos recovered at 12.5 dpc.|||This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner.|||cytosol http://togogenome.org/gene/10090:Rab11b ^@ http://purl.uniprot.org/uniprot/P46638 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in brain, heart and testis. Also detected in kidney and pancreatic islets.|||Belongs to the small GTPase superfamily. Rab family.|||Citrullinated by PADI4.|||Interacts with KCNMA1 (PubMed:22935415). Interacts with RAB11FIP1, RAB11FIP2, RAB11FIP3 and RAB11FIP4 (By similarity). May interact with TBC1D14 (By similarity). Interacts with ATP6V1E1 (By similarity). Interacts with PI4KB (By similarity). Interacts (GDP-bound form) with ZFYVE27 (By similarity). Interacts (GDP-bound form) with KIF5A in a ZFYVE27-dependent manner (By similarity). Interacts with RELCH (PubMed:29514919). Interacts (in GTP-bound form) with TBC1D8B (via domain Rab-GAP TBC) (By similarity). Forms a complex containing RAB11B, ASAP1, Rabin8/RAB3IP, RAP11FIP3 and ARF4. Interacts with WDR44 (By similarity).|||Recycling endosome membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The small Rab GTPase RAB11B plays a role in endocytic recycling, regulating apical recycling of several transmembrane proteins including cystic fibrosis transmembrane conductance regulator/CFTR, epithelial sodium channel/ENaC, potassium voltage-gated channel, and voltage-dependent L-type calcium channel. May also regulate constitutive and regulated secretion, like insulin granule exocytosis. Required for melanosome transport and release from melanocytes. Also regulates V-ATPase intracellular transport in response to extracellular acidosis. Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation. On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth (By similarity).|||phagosome membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Fbxo21 ^@ http://purl.uniprot.org/uniprot/Q8VDH1 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Supv3l1 ^@ http://purl.uniprot.org/uniprot/Q80YD1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family.|||Die in utero before midgestation. Show elevated sister chromatid exchange (SCE).|||Helicase activity toward DNA substrate is inhibited by micromolar concentrations of 5,6-dichloro-1-(beta-D-ribofuranosyl)benzotriazole (DRBT) and 4,5,6,7-tetrabromobenzotriazole (TBBT). Helicase activity toward RNA substrate is inhibited by elevated concentrations of TBBT. Inhibited by some ring-expanded nucleoside analogs.|||Homodimer; in free form. Component of the mitochondrial degradosome (mtEXO) complex which is a heteropentamer containing 2 copies of SUPV3L1 and 3 copies of PNPT1. As part of mitochondrial degradosome complex, interacts with GRSF1 in a RNA-dependent manner; the interaction enhances the activity of the complex. Interacts with LAMTOR5/HBXIP, WRN and BLM.|||Major helicase player in mitochondrial RNA metabolism. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Involved in the degradation of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules (By similarity). ATPase and ATP-dependent multisubstrate helicase, able to unwind double-stranded (ds) DNA and RNA, and RNA/DNA heteroduplexes in the 5'-to-3' direction. Plays a role in the RNA surveillance system in mitochondria; regulates the stability of mature mRNAs, the removal of aberrantly formed mRNAs and the rapid degradation of non coding processing intermediates. Also implicated in recombination and chromatin maintenance pathways. May protect cells from apoptosis. Associates with mitochondrial DNA.|||Mitochondrion matrix|||Nucleus|||mitochondrion nucleoid http://togogenome.org/gene/10090:Or9s23 ^@ http://purl.uniprot.org/uniprot/Q8VGU3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prpf3 ^@ http://purl.uniprot.org/uniprot/Q922U1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the precatalytic spliceosome (spliceosome B complex) (By similarity). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (By similarity). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (By similarity). Interacts directly with PRPF4 (By similarity). Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA (By similarity). Interacts with SART3; the interaction is direct and recruits the deubiquitinase USP4 to PRPF3 (By similarity). Interacts with PRPF19 (By similarity). Interacts ('Lys-63'-linked polyubiquitinated) with PRPF8 (via the MPN (JAB/Mov34) domain); may stabilize the U4/U6-U5 tri-snRNP complex (By similarity). Interacts with ERCC6 (By similarity).|||Nucleus|||Nucleus speckle|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).|||Ubiquitinated. Undergoes 'Lys-63'-linked polyubiquitination by PRPF19 and deubiquitination by USP4. 'Lys-63'-linked ubiquitination increases the affinity for PRPF8 and may regulate the assembly of the U4/U6-U5 tri-snRNP complex. http://togogenome.org/gene/10090:Nek1 ^@ http://purl.uniprot.org/uniprot/P51954 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Binds to CBY2 (PubMed:12204287). Found in a complex with CFAP410, NEK1 and SPATA7 (By similarity). Interacts with CFAP410 (By similarity). Interacts (via Ser-997 phosphorylated form) with 14-3-3 proteins (PubMed:28235073).|||In female, expressed as follicles enter the secondary stage until ovulation occurs. In the male reproductive system, the expression is limited to spermatocytes and spermatids.|||Nucleus|||Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity (PubMed:1382974). Involved in DNA damage checkpoint control and for proper DNA damage repair (PubMed:18843199). In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death (By similarity). May be implicated in the control of meiosis (PubMed:1382974). Involved in cilium assembly (By similarity).|||Predominantly in testes (germ cells and Sertoli cells). Lower levels in ovary (oocytes and granulosa cells), thymus and lung.|||centrosome http://togogenome.org/gene/10090:Sf3b3 ^@ http://purl.uniprot.org/uniprot/B2RSV4|||http://purl.uniprot.org/uniprot/Q921M3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RSE1 family.|||Identified in the spliceosome A complex; remains associated with the spliceosome throughout the splicing process. Component of the spliceosome B complex. Identified in the spliceosome C complex. Identified in the spliceosome E complex. Component of the minor spliceosome, also called U12-type spliceosome. Within this complex, interacts with SCNM1 (By similarity). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42. SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP). Interaction between SF3B3 and SF3B1 is tighter than the interaction between SF3B3 and SF3B2. Within the SF3B complex interacts directly with SF3B1 (via HEAT domain), SF3B5 and PHF5A. The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2. Associates with the STAGA transcription coactivator-HAT complex. Interacts with SUPT3H. Interacts with TAF3.|||Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex, a constituent of the spliceosome. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA. May also be involved in the assembly of the 'E' complex. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus|||The core of the protein consists of three beta-propeller domains. http://togogenome.org/gene/10090:Sft2d1 ^@ http://purl.uniprot.org/uniprot/Q5SSN7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SFT2 family.|||May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.|||Membrane http://togogenome.org/gene/10090:Evc ^@ http://purl.uniprot.org/uniprot/P57680 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Component of the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE (PubMed:24582806). Interacts with EVC2 (PubMed:24582806, PubMed:21356043). Interacts with EFCAB7 (PubMed:24582806). Interacts with IQCE (PubMed:24582806).|||Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling (PubMed:17660199, PubMed:24582806). Involved in endochondral growth and skeletal development (PubMed:17660199).|||Expressed in the developing skeleton and the orofacial region. Expression is general to all the cartilaginous components of the skeleton, including the chondrocranium, the vertebrae, the rib cage, and the axial skeleton by 15.5 dpc.|||cilium|||cilium basal body|||cilium membrane http://togogenome.org/gene/10090:Commd8 ^@ http://purl.uniprot.org/uniprot/Q9CZG3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B.|||Nucleus http://togogenome.org/gene/10090:Vmn2r51 ^@ http://purl.uniprot.org/uniprot/L7N215 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Asb7 ^@ http://purl.uniprot.org/uniprot/C0H5Y0|||http://purl.uniprot.org/uniprot/Q91ZU0 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Interacts with CUL5 and RNF7.|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Myef2 ^@ http://purl.uniprot.org/uniprot/Q8C854 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in the brain.|||Monomer.|||Nucleus|||Transcriptional repressor of the myelin basic protein gene (MBP). Binds to the proximal MB1 element 5'-TTGTCC-3' of the MBP promoter. Its binding to MB1 and function are inhibited by PURA. http://togogenome.org/gene/10090:Glis1 ^@ http://purl.uniprot.org/uniprot/Q8K1M4 ^@ Biotechnology|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as both a repressor and activator of transcription (PubMed:12042312, PubMed:12385751, PubMed:21654807). Binds to the consensus sequence 5'-GACCACCCAC-3' (PubMed:12042312). By controlling the expression of genes involved in cell differentiation inhibits the lineage commitment of multipotent cells (PubMed:21654807, PubMed:30544251). Prevents, for instance, the differentiation of multipotent mesenchymal cells into adipocyte and osteoblast (PubMed:30544251).|||Belongs to the GLI C2H2-type zinc-finger protein family.|||Higher expression is detected in unfertilized eggs and one-cell embryos compared to two-cells embryos and adult tissues (PubMed:21654807). In the embryo, expression is detected at 10 dpc becoming stronger by 11 dpc and continuing through to 16.5 dpc.|||In the adult, expressed highly in placenta and kidney and at lower levels in the testis, brain, colon, brown fat tissue and thymus. During embryo development, expressed in the frontal nasal region, branchial arches, somites, vibrissal and hair follicles, limb buds, craniofacial regions, ventral part of the tail, intervertebral disks, teeth, eyes and kidney.|||Interacts with KLF4. Interacts with POU5F1 and/or POU5F1B. Interacts with SOX2.|||No visible phenotype.|||Nucleus|||The combined transgenic expression of the OSK transcription factors POU5F1/OCT4, SOX2 and KLF4, reprograms differentiated cells into induced pluripotent stem cells/iSPCs. iPSCs exhibit the morphology and properties of embryonic stem/ES cells. The coexpression of GLIS1 can increase the efficiency of OSK-induced pluripotent stem cells/iPSCs production. http://togogenome.org/gene/10090:Pramel14 ^@ http://purl.uniprot.org/uniprot/A2ASJ1 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Smarca2 ^@ http://purl.uniprot.org/uniprot/F2Z4A9|||http://purl.uniprot.org/uniprot/H3BK47|||http://purl.uniprot.org/uniprot/Q6DIC0|||http://purl.uniprot.org/uniprot/Q9D007 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3 (By similarity). Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Interacts with PHF10/BAF45A (By similarity). Interacts with CEBPB (when not methylated) (PubMed:20111005). Interacts with TOPBP1 (By similarity). Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Interacts with DPF2 (By similarity). Interacts with ERCC6 (By similarity).|||During apoptosis, cleaved by cathepsin CTSG to produce a 160 kDa cleavage product which localizes to the cytosol.|||Expressed in the cortex and the hippocampus. Expressed in the cortical plate in the embryo.|||Impaired social interaction and prepulse inhibition.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.|||Nucleus|||Ubiquitinated. http://togogenome.org/gene/10090:Fastkd5 ^@ http://purl.uniprot.org/uniprot/Q7TMV3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAST kinase family.|||Expression detected in spleen, testis, colon, heart, smooth muscle, kidney, brain, lung, liver, brown and white adipose tissue.|||Found in a complex with GRSF1, DDX28, DHX30 and FASTKD2. Associates with the 12S mitochondrial rRNA (12S mt-rRNA).|||Plays an important role in the processing of non-canonical mitochondrial mRNA precursors.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Zfp276 ^@ http://purl.uniprot.org/uniprot/Q8CE64 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at low levels in all stages of embryonic development examined.|||Found in all the examined tissues, with highest levels in kidney, liver, lung, and spleen.|||May be involved in transcriptional regulation.|||Nucleus|||kinetochore http://togogenome.org/gene/10090:Lgr6 ^@ http://purl.uniprot.org/uniprot/Q3UVD5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the earliest embryonic hair placodes. In adult hair follicles, present in a region directly above the follicle bulge. Specifically present in prenatal cells establishing the hair follicle, sebaceous gland and interfollicular epidermis. Postnatally, present in cells generating sebaceous gland and interfollicular epidermis (PubMed:20223988). During limb development, at 14.5 dpc, expressed in the ectoderm overlying the limb buds and at the apical ectodermal ridge. In the developing lungs, at 14.5 dpc, expressed in smooth muscle cells (PubMed:29769720).|||Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a marker of multipotent stem cells in the epidermis. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal (By similarity).|||Simultaneous knockdown of LGR4, LGR5 and LGR6 results in developmental phenotypes, such as cleft palate and ankyloglossia, but not in tetra-amelia with lung agenesis.|||Specifically expressed in multipotent stem cells in the epidermis. http://togogenome.org/gene/10090:Nap1l1 ^@ http://purl.uniprot.org/uniprot/P28656 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleosome assembly protein (NAP) family.|||Cytoplasm|||During brain development, expression decreases from 12 dpc to P0. Expressed predominantly but not restricted in the ventricular zone (VZ)/subventricular zone (SVZ), and peak expression is observed at 12.5 dpc, in which the cerebral cortex consists primarily of neural progenitor cells (NPCs). At 15.5 dpc, the expression decreases in the cerebral cortical plate. At 18.5 dpc, when the embryonic neurogenesis period nears its end, the expression throughout the cerebral cortex is lower than that at 12.5 dpc (at protein level).|||Highly expressed in the brain (at protein level) (PubMed:29490266). High expression in cerebral cortex, not in cerebellar cortex.|||Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly. Participates also in several important DNA repair mechanisms: greatly enhances ERCC6-mediated chromatin remodeling which is essential for transcription-coupled nucleotide excision DNA repair. Stimulates also homologous recombination (HR) by RAD51 and RAD54 which is essential in mitotic DNA double strand break (DSB) repair (By similarity). Plays a key role in the regulation of embryonic neurogenesis (PubMed:29490266). Promotes the proliferation of neural progenitors and inhibits neuronal differentiation during cortical development (PubMed:29490266). Regulates neurogenesis via the modulation of RASSF10; regulates RASSF10 expression by promoting SETD1A-mediated H3K4 methylation at the RASSF10 promoter (PubMed:29490266).|||Homodimer. The dimer binds strongly and sequentially to single and double H2A-H2B heterodimers. Interacts with ERCC6; this interaction increases ERCC6 processivity. Interacts with RAD54 (By similarity). Interacts with SETD1A (PubMed:29490266).|||Melanosome|||Mice show abnormal embryonic neurogenesis.|||Nucleus|||Polyglutamylated by TTLL4 on glutamate residues, resulting in polyglutamate chains on the gamma-carboxyl group. Both polyglutamylation and polyglycylation modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally.|||Polyglycylated by TTLL10 on glutamate residues, resulting in polyglycine chains on the gamma-carboxyl group. Both polyglutamylation and polyglycylation modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally.|||The NAP1L motif is required for the histone chaperone activity.|||The acidic domains are probably involved in the interaction with histones. http://togogenome.org/gene/10090:Chst10 ^@ http://purl.uniprot.org/uniprot/A2RSS2|||http://purl.uniprot.org/uniprot/Q6PGK7 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfotransferase 2 family.|||Catalyzes the transfer of sulfate from 3'-phosphoadenylyl sulfate (PAPS) to position 3 of terminal glucuronic acid of both protein- and lipid-linked oligosaccharides. Participates in biosynthesis of HNK-1 carbohydrate structure 3-O-sulfo-beta-D-GlcA-(1->3)-beta-D-Gal-(1->4)-D-GlcNAc-R, a sulfated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, which is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult. May be indirectly involved in synapse plasticity of the hippocampus, via its role in HNK-1 biosynthesis (PubMed:12213450, PubMed:12358771). Sulfates terminal glucuronyl residue of the laminin globular (LG)-domain binding epitope on DAG1/alpha-dystroglycan and prevents further polymerization by LARGE1 glycosyltransferase. Likely defines the chain length of LG epitope, confering binding specificity to extracellular matrix components (By similarity). Plays a role in down-regulating the steroid hormones. Sulfates glucuronidated estrogens and androgens with an impact in hormone cycle and fertility. Has a preference for glucuronyl moiety at the 3-hydroxyl group of a sterol ring rather than the 17-hydroxyl group, showing high catalytic efficiency for 17beta-estradiol 3-O-(beta-D-glucuronate) and dehydroepiandrosterone 3-O-(beta-D-glucuronate) hormones (PubMed:23269668) (By similarity).|||Golgi apparatus membrane|||Intron retention.|||Membrane|||Mice are viable, fertile and show normal cerebellar granule neuron migration. The anatomy of all major brain areas are histologically normal. However, basal synaptic transmission in pyramidal cells in the CA1 region of the hippocampus are increased and long-term potentiation evoked by theta-burst stimulation are reduced. Mice show an impaired long-term memory and a poorer spatial learning when a short inter-trial interval is used (PubMed:12213450, PubMed:12358771). Mutant female mice are subfertile, have extensive growth of endometrial epithelium associated with increased 17-beta-estradiol levels at pro-estrus phase and dysregulated hormonal cycle (PubMed:23269668). http://togogenome.org/gene/10090:Wt1 ^@ http://purl.uniprot.org/uniprot/Q199A7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the EGR C2H2-type zinc-finger protein family.|||Cytoplasm|||Nucleus speckle http://togogenome.org/gene/10090:Supt6 ^@ http://purl.uniprot.org/uniprot/Q62383 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPT6 family.|||Interacts with RNA polymerase II and the DRB sensitivity-inducing factor complex (DSIF complex), which is composed of SUPT5H and SUPT4H1 or SUPT4H2 (By similarity). Interacts with PAAF1 (By similarity). Interacts with histone H2B and H3 (By similarity). Interacts (via SH2 domain) with POLR2A phosphorylated at 'Ser-2'. Interacts (via SH2 domain) with SETD1A. Interacts with IWS1, KDM6A and AICDA. Interacts with WDR43 (PubMed:31128943).|||Nucleus|||Transcription elongation factor which binds histone H3 and plays a key role in the regulation of transcription elongation and mRNA processing. Enhances the transcription elongation by RNA polymerase II (RNAPII) and is also required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. Besides chaperoning histones in transcription, acts to transport and splice mRNA by forming a complex with IWS1 and the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2), to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. SUPT6H via its association with SETD1A, regulates both class-switch recombination and somatic hypermutation through formation of H3K4me3 epigenetic marks on activation-induced cytidine deaminase (AICDA) target loci. Promotes the activation of the myogenic gene program by entailing erasure of the repressive H3K27me3 epigenetic mark through stabilization of the chromatin interaction of the H3K27 demethylase KDM6A.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Dnajc7 ^@ http://purl.uniprot.org/uniprot/Q9QYI3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as co-chaperone regulating the molecular chaperones HSP70 and HSP90 in folding of steroid receptors, such as the glucocorticoid receptor and the progesterone receptor. Proposed to act as a recycling chaperone by facilitating the return of chaperone substrates to early stages of chaperoning if further folding is required. In vitro, induces ATP-independent dissociation of HSP90 but not of HSP70 from the chaperone-substrate complexes (By similarity). Recruits NR1I3 to the cytoplasm.|||Associates with complexes containing chaperones HSP70 and HSP90. Interacts with the GAP domain of NF1. Interacts with HSP90AA1. Interacts with HSPA1A/B; the interaction is enhanced by ATP. Interacts with HSP90AB1. Interacts with PGR. Interacts with RAD9A; the interaction is interrupted by UV and heat shock treatments. Interacts with HUS1 and RAD1 (By similarity). Interacts with NR1I3; this complex may also include HSP90 Interacts with HSPA8 (By similarity).|||Cytoplasm|||Nucleus|||Widely expressed with high levels in liver, skeletal muscle, kidney and testis.|||cytoskeleton http://togogenome.org/gene/10090:Sra1 ^@ http://purl.uniprot.org/uniprot/Q80VJ2 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to be the first example of a new class of functional RNAs also able to encode a protein.|||Belongs to the SRA1 family.|||Contaminating sequence.|||Cytoplasm|||Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N-terminal domain (AF-1) of steroid receptors. Also mediates transcriptional coactivation of steroid receptors ligand-dependently through the steroid-binding domain (AF-2). Enhances cellular proliferation and differentiation and promotes apoptosis in vivo. May play a role in tumorigenesis (By similarity).|||Nucleus|||SRA1 RNA exists in a ribonucleoprotein complex containing NCOA1. The RNA also forms a complex with PUS1 and RARG in the nucleus. Interacts with AR. http://togogenome.org/gene/10090:Zdhhc3 ^@ http://purl.uniprot.org/uniprot/Q8R173 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autopalmitoylated.|||Belongs to the DHHC palmitoyltransferase family.|||Golgi apparatus membrane|||Golgi-localized palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates (PubMed:15229235, PubMed:15603741, PubMed:16129400, PubMed:19001095, PubMed:23793055, PubMed:25253725, PubMed:26487721). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (Probable). Plays an important role in G protein-coupled receptor signaling pathways involving GNAQ and potentially other heterotrimeric G proteins by regulating their dynamic association with the plasma membrane (PubMed:19001095). Palmitoylates ITGA6 and ITGB4, thereby regulating the alpha-6/beta-4 integrin localization, expression and function in cell adhesion to laminin (By similarity). Plays a role in the TRAIL-activated apoptotic signaling pathway most probably through the palmitoylation and localization to the plasma membrane of TNFRSF10A (By similarity). In the brain, by palmitoylating the gamma subunit GABRG2 of GABA(A) receptors and regulating their postsynaptic accumulation, plays a role in synaptic GABAergic inhibitory function and GABAergic innervation (PubMed:15229235, PubMed:17151279, PubMed:27875292). Palmitoylates the neuronal protein GAP43 which is also involved in the formation of GABAergic synapses (PubMed:27875292). Palmitoylates NCDN thereby regulating its association with endosome membranes (PubMed:23687301). Probably palmitoylates PRCD and is involved in its proper localization within the photoreceptor (PubMed:27613864). Could mediate the palmitoylation of NCAM1 and regulate neurite outgrowth (PubMed:27247265). Could palmitoylate DNAJC5 and regulate its localization to Golgi membranes (PubMed:18596047). Also constitutively palmitoylates DLG4 (PubMed:15603741). May also palmitoylate SNAP25 (PubMed:25253725). Could palmitoylate the glutamate receptors GRIA1 and GRIA2 but this has not been confirmed in vivo (PubMed:16129400, PubMed:27875292). Could also palmitoylate the D(2) dopamine receptor DRD2 (By similarity). May also palmitoylate LAMTOR1, promoting its localization to lysosomal membranes (By similarity).|||Homozygous knockout mice are viable, fertile and do not display overt phenotype (PubMed:27875292). Male show a modest reduction in body weight (PubMed:27875292). Zdhhc3 and Zdhhc7 double knockout mice show a perinatally lethal phenotype (PubMed:27875292).|||May also function as a calcium transporter.|||Monomer (PubMed:23793055). Homooligomers (PubMed:17151279, PubMed:23793055). The monomeric form has a higher catalytic activity (PubMed:23793055). Forms heterooligomers with ZDHHC7 (PubMed:17151279). Interacts with TNFRSF10A (By similarity).|||Phosphorylation by FGFR1 and SRC probably regulates the palmitoyltransferase activity.|||The DHHC domain is required for palmitoyltransferase activity.|||Widely expressed, with highest levels in brain. In the brain, expressed only in neurons (at protein level). http://togogenome.org/gene/10090:Tmem63a ^@ http://purl.uniprot.org/uniprot/Q91YT8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as an osmosensitive calcium-permeable cation channel (PubMed:27045885). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938).|||Belongs to the CSC1 (TC 1.A.17) family.|||Cell membrane|||Lysosome membrane http://togogenome.org/gene/10090:Tmem175 ^@ http://purl.uniprot.org/uniprot/Q8BM80|||http://purl.uniprot.org/uniprot/Q9CXY1 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons (By similarity). Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity (By similarity). Proton channel activity is directly inhibited by LAMP1 or LAMP2, facilitating lysosomal acidification (By similarity). Channel activity is activated following interaction with AKT (AKT1, AKT2 or AKT3): interaction promotes activation from closed to an open state (PubMed:33505021). Activation by AKT is independent of AKT serine/threonine-protein kinase activity (PubMed:33505021).|||Belongs to the TMEM175 family.|||Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-43 in the first module and Ile-268 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity.|||Endosome membrane|||Homodimer (By similarity). Interacts with AKT (AKT1, AKT2 or AKT3); leading to formation of the lysoK(GF) complex, which activates the channel (PubMed:33505021). Interacts with LAMP1; inhibiting the proton channel activity of TMEM175 (By similarity). Interacts with LAMP2; inhibiting the proton channel activity of TMEM175 (By similarity).|||Lysosome membrane|||Membrane|||Mice display accelerated loss of dopaminergic neurons and impaired motor skills (PubMed:33505021). Knockout neurons show increased damage in response to insults and an accumulation of alpha-synuclein (PubMed:33505021, PubMed:35750034). The accumulation of alpha-synuclein leads to increased damage to the integrity of lysosomal membranes (PubMed:33505021, PubMed:35750034).|||Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH (PubMed:35750034). Activated at low pH (under pH 4.6) by luminal side protons: selectively mediates lysosomal proton release from lysosomes, eliciting a proton leak that balances V-ATPase activity to maintain pH homeostasis (By similarity). Regulation of lumenal pH stability is required for autophagosome-lysosome fusion (PubMed:26317472). May also act as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes (PubMed:26317472, PubMed:33505021). The potassium channel activity is however unclear as it was tested in non-physiological conditions for a lysosomal channel (By similarity). Constitutes the pore-forming subunit of the lysoK(GF) complex, a complex activated by extracellular growth factors (PubMed:33505021). The lysoK(GF) complex is composed of TMEM175 and AKT (AKT1, AKT2 or AKT3), a major target of growth factor receptors: in the complex, TMEM175 channel is opened by conformational changes by AKT, leading to its activation (PubMed:33505021). The lysoK(GF) complex is required to protect neurons against stress-induced damage (PubMed:33505021). http://togogenome.org/gene/10090:Naxe ^@ http://purl.uniprot.org/uniprot/Q8K4Z3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NnrE/AIBP family.|||Binds 1 potassium ion per subunit.|||Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX. Accelerates cholesterol efflux from endothelial cells to high-density lipoprotein (HDL) and thereby regulates angiogenesis (By similarity).|||Detected in testis and sperm (at protein level). Expressed at high levels in heart, liver, kidney, and testis.|||Homodimer (PubMed:18202122). Interacts with APOA1 and APOA2 (By similarity).|||Mitochondrion|||Secreted|||Undergoes physiological phosphorylation during sperm capacitation, downstream to PKA activation. http://togogenome.org/gene/10090:Spire1 ^@ http://purl.uniprot.org/uniprot/A0A5H1ZRL1|||http://purl.uniprot.org/uniprot/D3YTL8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the spire family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Membrane|||cytoskeleton http://togogenome.org/gene/10090:Irak2 ^@ http://purl.uniprot.org/uniprot/Q8CFA1 ^@ Caution|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Asn-333 is present instead of the conserved Asp which is expected to be an active site residue.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.|||Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization.|||Interacts with MYD88. IL-1 stimulation leads to the formation of a signaling complex which dissociates from the IL-1 receptor following the binding of PELI1 (By similarity).|||The protein kinase domain is predicted to be catalytically inactive.|||Ubiquitously expressed, with a higher expression observed in brain, spleen and liver. Isoform 1 and isoform 2 are considered agonist and isoform 3 and isoform 4 are considered antagonist. http://togogenome.org/gene/10090:Rhox4d ^@ http://purl.uniprot.org/uniprot/Q2MDG0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Faf2 ^@ http://purl.uniprot.org/uniprot/Q3TDN2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endoplasmic reticulum|||Identified in a complex that contains SEL1L, OS9, FAF2/UBXD8, UBE2J1/UBC6E and AUP1. Interacts with YOD1. Interacts (via N-terminus) with UBQLN2 (via C-terminus). Interacts with PNPLA2 (By similarity). Interacts with ZFAND2B; probably through VCP (PubMed:24160817). Interacts with LMBR1L and UBAC2 (PubMed:31073040).|||Lipid droplet|||Plays an important role in endoplasmic reticulum-associated degradation (ERAD) that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. Involved in inhibition of lipid droplet degradation by binding to phospholipase PNPL2 and inhibiting its activity by promoting dissociation of PNPL2 from its endogenous activator, ABHD5 which inhibits the rate of triacylglycerol hydrolysis. Involved in stress granule disassembly: associates with ubiquitinated G3BP1 in response to heat shock, thereby promoting interaction between ubiquitinated G3BP1 and VCP, followed by G3BP1 extraction from stress granules and stress granule disassembly. http://togogenome.org/gene/10090:Tmem108 ^@ http://purl.uniprot.org/uniprot/Q8BHE4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early endosome|||Endosome membrane|||Expressed in the nervous system tissues, such as hippocampus and spinal cord, is barely detectable in peripheral tissues such as heart, lung, liver, kidney and muscle (PubMed:17287360, PubMed:28096412). In brain, highly expressed in dentate gyrus neurons and expressed in cortex, olfactory bulb, ammon's horn, cerebellum, hypothalamus and striatum (PubMed:28096412, PubMed:21849472).|||Glycosylated.|||In brain, detectable as early as 12 dpc and the level increases persistently through later embryonic stages to the adult age (PubMed:17287360). In the hippocampus, undetectable at postnatal day 1 (P1), detected at P7, the levels peak between P15 and P21 to remain at a high level during adulthood (PubMed:28096412).|||Interacts with DST (isoform 1) (PubMed:17287360). Interacts with SH3GL2 (PubMed:21849472). Interacts (via N-terminus) with CYFIP1 and CYFIP2; the interactions associate TMEM108 with the WAVE1 complex (PubMed:27605705).|||Membrane|||Mutants are viable and show no difference in body weight or locomotor activity (PubMed:28096412). They are impaired in sensorimotor gating, spatial recognition memory and suppressed fear memory consolidation (PubMed:28096412). Spine density of dentate gyrus granule neurons is significantly reduced compare to wild-type animals, which is associated with decreased spine width and increased spine length (PubMed:28096412).|||Postsynaptic density|||Transmembrane protein required for proper cognitive functions. Involved in the development of dentate gyrus (DG) neuron circuitry, is necessary for AMPA receptors surface expression and proper excitatory postsynaptic currents of DG granule neurons (PubMed:28096412). Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Through the interaction with DST, mediates the docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport (PubMed:17287360). In hippocampal neurons, required for BDNF-dependent dendrite outgrowth (PubMed:21849472). Cooperates with SH3GL2 and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2 early endocytic trafficking and mediate signaling from early endosomes (PubMed:21849472, PubMed:27605705).|||axon|||dendrite http://togogenome.org/gene/10090:P2rx3 ^@ http://purl.uniprot.org/uniprot/Q3UR32 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the P2X receptor family.|||Cell membrane|||Homotrimer (By similarity). Functional P2XRs are organized as homomeric and heteromeric trimers (By similarity).|||Receptor for ATP that acts as a ligand-gated cation channel (By similarity). Plays a role in sensory perception (PubMed:15961431, PubMed:16322458). Required for normal perception of pain (PubMed:15961431). Required for normal taste perception (PubMed:16322458).|||Simultaneous knockout of P2rx2 and P2rx3 results in reduced pain-related behaviors in response to intraplantar injection of formalin and reduced urinary bladder reflexes and decreased pelvic afferent nerve activity in response to bladder distension. Neurons have minimal to no response to ATP (PubMed:15961431). Simultaneous knockout of P2rx2 and P2rx3 results in defects in taste responses in the taste nerves and reduced behavioral responses to sweeteners, glutamate and bitter substances (PubMed:16322458). http://togogenome.org/gene/10090:Hspb3 ^@ http://purl.uniprot.org/uniprot/Q9QZ57 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small heat shock protein (HSP20) family.|||Cytoplasm|||Inhibitor of actin polymerization.|||Nucleus http://togogenome.org/gene/10090:Ptpn5 ^@ http://purl.uniprot.org/uniprot/P54830 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cytoplasm|||Endoplasmic reticulum membrane|||Lacks the catalytic domain.|||May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors.|||Phosphorylation at Ser-221 by PKA deactivates PTPN5. Phosphorylation at Thr-231 and Ser-244 by MAPKs stabilizes the phosphatase, dephosphorylation of these sites results in ubiquitin-mediated degradation of the active phosphatase (By similarity).|||STEP20 is expressed only in the CNS. http://togogenome.org/gene/10090:Hrh4 ^@ http://purl.uniprot.org/uniprot/B2ZGH2|||http://purl.uniprot.org/uniprot/Q2M2N7|||http://purl.uniprot.org/uniprot/Q91ZY2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist) (By similarity). http://togogenome.org/gene/10090:Lrrc14b ^@ http://purl.uniprot.org/uniprot/Q3UJB3 ^@ Similarity ^@ Belongs to the PRAME family. LRRC14 subfamily. http://togogenome.org/gene/10090:Gpi1 ^@ http://purl.uniprot.org/uniprot/P06745 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GPI family.|||Cytoplasm|||Embryonic lethality caused by impaired gastrulation (PubMed:8922529). During early development, the egg cylinder fails to be divided into the three cavities, suggesting a deficiency in extraembryonic mesoderm formation resulting in the failure to form the amnion or chorionic mesoderm (PubMed:8922529).|||Homodimer in the catalytically active form, monomer in the secreted form.|||ISGylated.|||In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (PubMed:7277315, PubMed:2344351, PubMed:8417789). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility (By similarity). Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons (PubMed:3764429, PubMed:3352745). It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (PubMed:3352745).|||Secreted http://togogenome.org/gene/10090:Xpr1 ^@ http://purl.uniprot.org/uniprot/Q9Z0U0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ (Microbial infection) Receptor for xenotropic and polytropic murine leukemia (X- and P-MLV) retroviruses. Confers susceptibility to X- or P-MLV infection in vitro.|||Belongs to the SYG1 (TC 2.A.94) family.|||Cell membrane|||Expressed in pancreatic islets.|||Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated (PubMed:32826297) (By similarity). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux (By similarity).|||The SPX domain has high affinity for inositol polyphosphates, such as myo-inositol hexakisphosphate and 5-diphospho-myo-inositol pentakisphosphate (5-InsP7). Its affinity for inorganic phosphate is tow to three orders of magnitude lower. http://togogenome.org/gene/10090:Mblac1 ^@ http://purl.uniprot.org/uniprot/Q8BWY4 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||Binds 2 Zn(2+) ions per subunit.|||Contains four of the five characteristic MBL-fold metal-binding motifs, with two waters completing metal coordination.|||Endoribonuclease that catalyzes the hydrolysis of histone-coding pre-mRNA 3'-end. Involved in histone pre-mRNA processing during the S-phase of the cell cycle, which is required for entering/progressing through S-phase. Cleaves histone pre-mRNA at a major and a minor cleavage site after the 5'-ACCCA-3' and the 5'-ACCCACA-3' sequence, respectively, and located downstream of the stem-loop. May require the presence of the HDE element located at the histone pre-RNA 3'-end to avoid non-specific cleavage.|||Homodimer.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Rps4x ^@ http://purl.uniprot.org/uniprot/P62702|||http://purl.uniprot.org/uniprot/Q545F8|||http://purl.uniprot.org/uniprot/Q545X8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS4 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:4930480E11Rik ^@ http://purl.uniprot.org/uniprot/Q0VG34|||http://purl.uniprot.org/uniprot/Q9D5A6 ^@ Similarity ^@ Belongs to the FAM47 family. http://togogenome.org/gene/10090:Mapk14 ^@ http://purl.uniprot.org/uniprot/P47811|||http://purl.uniprot.org/uniprot/Q5U421 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-53 and Lys-152 by KAT2B and EP300. Acetylation at Lys-53 increases the affinity for ATP and enhances kinase activity. Lys-53 and Lys-152 are deacetylated by HDAC3 (By similarity).|||Activated by cell stresses such as DNA damage, heat shock, osmotic shock, anisomycin and sodium arsenite, as well as pro-inflammatory stimuli such as bacterial lipopolysaccharide (LPS) and interleukin-1. Activation occurs through dual phosphorylation of Thr-180 and Tyr-182 by either of two dual specificity kinases, MAP2K3/MKK3 or MAP2K6/MKK6, and potentially also MAP2K4/MKK4, as well as by TAB1-mediated autophosphorylation. MAPK14 phosphorylated on both Thr-180 and Tyr-182 is 10-20-fold more active than MAPK14 phosphorylated only on Thr-180, whereas MAPK14 phosphorylated on Tyr-182 alone is inactive. whereas Thr-180 is necessary for catalysis, Tyr-182 may be required for auto-activation and substrate recognition. Phosphorylated at Tyr-323 by ZAP70 in an alternative activation pathway in response to TCR signaling in T-cells. This alternative pathway is inhibited by GADD45A. Inhibited by dual specificity phosphatases, such as DUSP1, DUSP10, and DUSP16. Specifically inhibited by the binding of pyridinyl-imidazole compounds, which are cytokine-suppressive anti-inflammatory drugs (CSAID). SB203580 is an inhibitor of MAPK14.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (By similarity). Binds to a kinase interaction motif within the protein tyrosine phosphatase, PTPRR (By similarity). This interaction retains MAPK14 in the cytoplasm and prevents nuclear accumulation (By similarity). Interacts with SPAG9 and GADD45A (By similarity). Interacts with CDC25B, CDC25C, DUSP1, DUSP10, DUSP16, NP60, SUPT20H and TAB1. Interacts with casein kinase II subunits CSNK2A1 and CSNK2B. Interacts with PPM1D. Interacts with CDK5RAP3; recruits PPM1D to MAPK14 and may regulate its dephosphorylation (By similarity). Interacts with DUSP2; this interaction does not lead to catalytic activation of DUSP2 and dephosphrylation of MAPK14 (PubMed:16288922).|||Cytoplasm|||Dually phosphorylated on Thr-180 and Tyr-182 by the MAP2Ks MAP2K3/MKK3, MAP2K4/MKK4 and MAP2K6/MKK6 in response to inflammatory cytokines, environmental stress or growth factors, which activates the enzyme. Dual phosphorylation can also be mediated by TAB1-mediated autophosphorylation. TCR engagement in T-cells also leads to Tyr-323 phosphorylation by ZAP70. Dephosphorylated and inactivated by DUPS1, DUSP10 and DUSP16. PPM1D also mediates dephosphorylation and inactivation of MAPK14 (By similarity).|||Macrophages, monocytes, T- and B-lymphocytes. Isoform 2 is specifically expressed in kidney and liver.|||Nucleus|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1. RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2. MAPK14 interacts also with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53. In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3. MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9. Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A. The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation. Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation. The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression. Phosphorylates S100A9 at 'Thr-113' (By similarity).|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.|||Ubiquitinated. Ubiquitination leads to degradation by the proteasome pathway (By similarity). http://togogenome.org/gene/10090:Ogdhl ^@ http://purl.uniprot.org/uniprot/B2RXT3|||http://purl.uniprot.org/uniprot/E9Q7L0 ^@ Similarity ^@ Belongs to the alpha-ketoglutarate dehydrogenase family. http://togogenome.org/gene/10090:Nsg2 ^@ http://purl.uniprot.org/uniprot/P47759|||http://purl.uniprot.org/uniprot/Q5SS02 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NSG family.|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Endosome membrane|||Golgi stack membrane|||Highly expressed at 20 dpc. At 17.5 dpc, highly expressed in the cortical plate and basal subventricular zone.|||Late endosome membrane|||Lysosome lumen|||Membrane|||Specifically expressed in neural and neuroendocrine tissues. Pituitary and less in adrenal gland and testis. Expressed in the hippocampus throughout development. Remains enriched in layer V cortical neurons during development. At P0, broadly expressed in the neocortex. Is down-regulated overall at P8 and P14, but remains relatively enriched in layer V. At P0 is lower expressed in the cerebellum. Expression remains low throughout development, and is undetectable by adulthood (PubMed:28299779).|||dendrite|||multivesicular body membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Gspt1 ^@ http://purl.uniprot.org/uniprot/Q8CCV1|||http://purl.uniprot.org/uniprot/Q8R050 ^@ Function|||Similarity|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.|||Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. ERF3 subfamily.|||Component of the eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and ERF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. The ETF1-GSPT1 complex interacts with JMJD4 (By similarity). Interacts with PABPC1 (Ref.7). Interacts with SHFL (By similarity).|||GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA. GSPT1/ERF3A mediates ETF1/ERF1 delivery to stop codons: The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site. GTP hydrolysis by GSPT1/ERF3A induces a conformational change that leads to its dissociation, permitting ETF1/ERF1 to accommodate fully in the A-site. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes. http://togogenome.org/gene/10090:Or8s2 ^@ http://purl.uniprot.org/uniprot/Q8VGU2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn2r121 ^@ http://purl.uniprot.org/uniprot/A2BE32 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Poglut3 ^@ http://purl.uniprot.org/uniprot/G5E897 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the KDELC family.|||Endoplasmic reticulum lumen|||Protein glucosyltransferase that catalyzes the transfer of glucose from UDP-glucose to a serine residue within the consensus sequence peptide C-X-N-T-X-G-S-F-X-C. Can also catalyze the transfer of xylose from UDP-xylose but less efficiently. Specifically targets extracellular EGF repeats of proteins such as NOTCH1, NOTCH3, FBN1, FBN2 and LTBP1. May regulate the transport of NOTCH1 and NOTCH3 to the plasma membrane and thereby the Notch signaling pathway. http://togogenome.org/gene/10090:Or1o2 ^@ http://purl.uniprot.org/uniprot/Q8VFE1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mcm9 ^@ http://purl.uniprot.org/uniprot/Q2KHI9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MCM family.|||By E2F1 and serum stimulation.|||Chromosome|||Component of the MCM8-MCM9 complex, a complex involved in the repair of double-stranded DNA breaks (DBSs) and DNA interstrand cross-links (ICLs) by homologous recombination (HR) (PubMed:23401855, PubMed:22771120). Required for DNA resection by the MRE11-RAD50-NBN/NBS1 (MRN) complex at double-stranded DNA breaks to generate ssDNA by recruiting the MRN complex to the repair site and by promoting the complex nuclease activity (By similarity). Probably by regulating the localization of the MNR complex, indirectly regulates the recruitment of downstream effector RAD51 to DNA damage sites including DBSs and ICLs (PubMed:22771120, PubMed:23401855). Acts as a helicase in DNA mismatch repair (MMR) following DNA replication errors to unwind the mismatch containing DNA strand (PubMed:22771120, PubMed:26300262). In addition, recruits MLH1, a component of the MMR complex, to chromatin (By similarity). The MCM8-MCM9 complex is dispensable for DNA replication and S phase progression (PubMed:21987787). Probably by regulating HR, plays a key role during gametogenesis (PubMed:21987787, PubMed:22771120).|||Component of the MCM8-MCM9 complex, which forms a hexamer composed of MCM8 and MCM9 (PubMed:22771120). Interacts with the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (By similarity). Interacts with MLH1; the interaction recruits MLH1 to chromatin (By similarity). Interacts with MSH2; the interaction recruits MCM9 to chromatin (By similarity). Interacts with MSH6 (By similarity). Interacts with the MRN complex composed of MRE11, RAD50 and NBN/NBS1; the interaction recruits the MRN complex to DNA damage sites (By similarity). Interacts with RAD51; the interaction recruits RAD51 to DNA damage sites (By similarity).|||Expressed in embryos and adults.|||Females are viable but are sterile due to defects in double-strand break repair during gametogenesis. Males are not sterile and produce spermatozoa, but in much reduced quantity. Female ovaries are completely devoid of oocytes, and testes show a severe early proliferation defect of germ cells, causing a retarded development of only a fraction of seminiferous tubules that produce then apparently normal spermatozoa.|||Incomplete sequence.|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Phox2a ^@ http://purl.uniprot.org/uniprot/Q62066 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the paired homeobox family.|||May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes. Acts as a transcription activator/factor. Could maintain the noradrenergic phenotype (By similarity).|||Nucleus http://togogenome.org/gene/10090:Foxs1 ^@ http://purl.uniprot.org/uniprot/Q4VA05|||http://purl.uniprot.org/uniprot/Q61574 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Accumulation of blood in the central part of the fetal testis. Increased ectopic apoptosis in periendothelial cells of the testis.|||Expressed in the testis in Sertoli and periendothelial cells at 14 dpc.|||Nucleus|||Transcriptional repressor that suppresses transcription from the FASLG, FOXO3 and FOXO4 promoters. May have a role in the organization of the testicular vasculature. http://togogenome.org/gene/10090:Cnep1r1 ^@ http://purl.uniprot.org/uniprot/Q3UJ81 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CNEP1R1 family.|||Cytoplasm|||Forms with the serine/threonine protein phosphatase CTDNEP1 an active complex which dephosphorylates and may activate LPIN1 and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol (By similarity).|||Interacts with CTDNEP1; the complex dephosphorylates LPIN1 and LPIN2.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Muscle specific with lower expression in other metabolic tissues.|||Nucleus membrane http://togogenome.org/gene/10090:E330014E10Rik ^@ http://purl.uniprot.org/uniprot/Q3UL33 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Riok2 ^@ http://purl.uniprot.org/uniprot/Q9CQS5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with late 40S pre-ribosomal particles. Interacts with PLK1 (via its N-terminus).|||Autophosphorylated (in vitro). Phosphorylation affects the timing of the metaphase-anaphase transition.|||Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.|||Cytoplasm|||Serine/threonine-protein kinase involved in the final steps of cytoplasmic maturation of the 40S ribosomal subunit. Involved in export of the 40S pre-ribosome particles (pre-40S) from the nucleus to the cytoplasm. Its kinase activity is required for the release of NOB1, PNO1 and LTV1 from the late pre-40S and the processing of 18S-E pre-rRNA to the mature 18S rRNA. May regulate the timing of the metaphase-anaphase transition during mitotic progression, and its phosphorylation, may regulate this function. http://togogenome.org/gene/10090:Lpar6 ^@ http://purl.uniprot.org/uniprot/Q8BMC0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Binds to oleoyl-L-alpha-lysophosphatidic acid (LPA). Intracellular cAMP is involved in the receptor activation. Important for the maintenance of hair growth and texture (By similarity).|||Cell membrane|||Ubiquitously expressed. Detected in the hair follicles and skin (at protein level). http://togogenome.org/gene/10090:Or5b118 ^@ http://purl.uniprot.org/uniprot/Q7TQQ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tef ^@ http://purl.uniprot.org/uniprot/Q9JLC6 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates according to a robust circadian rhythm in liver and kidney. In liver nuclei, the amplitude of daily oscillation has been estimated to be 9-fold. Expressed at nearly constant level in the brain.|||Belongs to the bZIP family. PAR subfamily.|||Binds DNA as a homodimer or a heterodimer. Can form a heterodimer with DBP (By similarity).|||Isoform Alpha and isoform Beta are expressed at high levels in lung, bladder, kidney, gut and brain.|||Mice deficient for all three PAR bZIP proteins (DBP, HLF and TEF) display a dramatically shortened life span and are highly susceptible to generalized spontaneous and audiogenic epilepsies (due for example to the noise of a vacuum cleaner) that are frequently lethal. The down-regulation of pyridoxal kinase (Pdxk) expression in these mice may participate in this seizure phenotype.|||Nucleus|||Transcription factor that binds to and transactivates the TSHB promoter. Binds to a minimal DNA-binding sequence 5'-[TC][AG][AG]TTA[TC][AG]-3' (By similarity). Also activates the telokin promoter in smooth muscle-specific and calcium-dependent manner. http://togogenome.org/gene/10090:Gmds ^@ http://purl.uniprot.org/uniprot/Q8K0C9 ^@ Activity Regulation|||Function|||Similarity ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.|||Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose.|||Inhibited by GDP-fucose. http://togogenome.org/gene/10090:Ubiad1 ^@ http://purl.uniprot.org/uniprot/Q9DC60 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UbiA prenyltransferase family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with HMGCR and SOAT1.|||Mitochondrion membrane|||Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. MK-4 is a vitamin K2 isoform required for endothelial cell development. Mediates the conversion of phylloquinone (PK) into MK-4, probably by cleaving the side chain of phylloquinone (PK) to release 2-methyl-1,4-naphthoquinone (menadione; K3) and then prenylating it with geranylgeranyl pyrophosphate (GGPP) to form MK-4. Also plays a role in cardiovascular development independently of MK-4 biosynthesis, by acting as a coenzyme Q10 biosynthetic enzyme: coenzyme Q10, also named ubiquinone, plays an important antioxidant role in the cardiovascular system. Mediates biosynthesis of coenzyme Q10 in the Golgi membrane, leading to protect cardiovascular tissues from NOS3/eNOS-dependent oxidative stress. http://togogenome.org/gene/10090:Eif5 ^@ http://purl.uniprot.org/uniprot/P59325|||http://purl.uniprot.org/uniprot/Q3TQR3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-2-beta/eIF-5 family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. In this complex, acts as a GTPase-activating protein, by promoting GTP hydrolysis by eIF2G (EIF2S3). During scanning, interacts with both EIF1 (via its C-terminal domain (CTD)) and EIF1A (via its NTD). This interaction with EIF1A contributes to the maintenance of EIF1 within the open 43S PIC. When start codon is recognized, EIF5, via its NTD, induces eIF2G (EIF2S3) to hydrolyze the GTP. Start codon recognition also induces a conformational change of the PIC to a closed state. This change increases the affinity of EIF5-CTD for EIF2-beta (EIF2S2), which allows the release, by an indirect mechanism, of EIF1 from the PIC. Finally, EIF5 stabilizes the PIC in its closed conformation.|||Component of the 43S pre-initiation complex (43S PIC), which is composed of the 40S ribosomal subunit, EIF1, eIF1A (EIF1AX), eIF3 complex, EIF5 and eIF2-GTP-initiator tRNA complex (eIF2 ternary complex). Interacts with eIF1A (EIF1AX) during scanning. Interacts through its C-terminal domain (CTD) with EIF1 or with eIF2-beta (EIF2S2) (mutually exclusive) through a common binding site. Interacts through its C-terminal domain (CTD) with the CTD of EIF5B. Interacts with FMR1 isoform 6; this interaction occurs in a RNA-dependent manner.|||Cytoplasm http://togogenome.org/gene/10090:Or5w8 ^@ http://purl.uniprot.org/uniprot/Q8VFQ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ceacam2 ^@ http://purl.uniprot.org/uniprot/Q925P2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. CEA family.|||Cell membrane|||Controls energy balance and peripheral insulin action. Involved in the regulation of feeding behavior particularly in the ventromedial nucleus of hypothalamus (VMH) regulation of food intake. Has a role in the regulation of metabolic rate and insulin sensitivity or resistance via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle. In case of murine coronavirus (MHV) infection, does probably not serve as functional receptor for the virus.|||Expressed throughout embryonic development. Isoform 2 first appears faintly in the testis 3 weeks into postnatal development and its expression level increases after 5 weeks.|||Interacts weakly with MHV spike protein in tissue culture.|||Isoform 2 is detected in elongating spermatids within the seminiferous epithelium (at protein level). Expressed in kidney, colon, uterus, gut mononuclear cells, crypt epithelia of intestinal tissues, and to a lesser extent, in spleen. Expressed in brain including VMH, globus pallidus, ventral pallidum, striatum, olfactory bulb and hippocampus. Also detected in rectal carcinoma cell line CMT93. Isoform 2 and isoform 3 are expressed in testis. Isoform 2 is detected in seminiferous tubule, not detected in epididymal spermatozoa. Also not observed on spermatogonia, spermatocytes, round spermatids or somatic Sertoli cells. During stages I-VII of spermatogenesis, detected on the elongating spermatids. At spermiation (stage VIII) and subsequent stages IX-XII, levels are drastically reduced or absent in the seminiferous tubules. Sometimes weakly detected in the apical region of stage-VIII seminiferous epithelium. Isoform 2 level is very low in stomach, kidney, intestine, liver and spleen.|||Isoform 2 may be an adhesion molecule contributing to cell to cell adhesion between elongating spermatids and Sertoli cells within the seminiferous epithelium.|||Levels in brain increase at fasting and decrease at 4 and 7 hours of refeeding.|||Sexually dimorphic effect. Homozygous null mutant female mice exhibit obesity that results from hyperphagia and reduced energy expenditure. Hyperphagia leads to peripheral insulin resistance. Insulin action is normal in liver but is compromised in skeletal muscle; the mice have incomplete fatty acid oxidation and impaired glucose uptake and disposal. Hyperphagia appears to result partly from increased hyperinsulinemia-induced hypothalamic fatty acid synthase levels and activity. Hyperinsulinemia is caused by increased insulin secretion. Homozygous null mutant male mice show total fat mass reduction, which ows to the hypermetabolic state despite hyperphagia. They also exhibit insulin sensitivity with elevated beta-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Both males and females have increased brown adipogenesis. However, only males have increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity.|||The human orthologous protein seems not to exist. In mice, both Ceacam1 and Ceacam2 are the paralogs of human CEACAM1. http://togogenome.org/gene/10090:B4galt3 ^@ http://purl.uniprot.org/uniprot/Q3U260|||http://purl.uniprot.org/uniprot/Q91YY2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 7 family.|||Golgi apparatus membrane|||Golgi stack membrane|||Membrane|||Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids. http://togogenome.org/gene/10090:Nkx2-4 ^@ http://purl.uniprot.org/uniprot/Q9EQM3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NK-2 homeobox family.|||Expressed in a restricted region of the posterior hypothalamus from 10 dpc. Detected in the head region from 12.5 dpc to 14.5 dpc. Expression is down-regulated by 15.5 dpc.|||In the embryo it is detected in the posterior hypothalamus and later in the head. In the adult it is detected only in testis.|||Nucleus|||Probable transcription factor. http://togogenome.org/gene/10090:Muc13 ^@ http://purl.uniprot.org/uniprot/P19467|||http://purl.uniprot.org/uniprot/Q3V1S6 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cleaved into two subunits, alpha and beta, probably between the first EGF domain and the SEA domain. Beta subunit contains the cytoplasmic tail and alpha subunit the extracellular tail. The homooligomerization into dimers is dependent on intrachain disulfide bonds (By similarity).|||Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling.|||Highly N-glycosylated.|||Homodimer of beta subunits.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Rbp7 ^@ http://purl.uniprot.org/uniprot/Q540P4|||http://purl.uniprot.org/uniprot/Q9EPC5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Highly expressed in white adipose tissue and mammary gland.|||Intracellular transport of retinol. http://togogenome.org/gene/10090:Upk1a ^@ http://purl.uniprot.org/uniprot/A2RSB9|||http://purl.uniprot.org/uniprot/Q9D132 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions (By similarity).|||Homodimer; disulfide-linked. Interacts with uroplakin-2 (UPK2) (By similarity). Binds to uropathogenic E.coli fimH.|||Membrane http://togogenome.org/gene/10090:Zbed4 ^@ http://purl.uniprot.org/uniprot/Q80WQ9 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in the thymus (PubMed:19369242). In the retina, expressed in the cone photoreceptors (PubMed:19369242, PubMed:22693546).|||Homodimer; via C-terminus (By similarity). Interacts with MYH9 (By similarity). Interacts with SAFB/SAFB1 (By similarity).|||Nucleus|||Photoreceptor inner segment|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||Transcriptional regulator that binds to poly-guanine tracts in gene promoters and activates transcription (By similarity). Able to bind single- and double-stranded DNA and RNA (PubMed:22693546). http://togogenome.org/gene/10090:Smyd5 ^@ http://purl.uniprot.org/uniprot/Q3TYX3 ^@ Function|||Induction|||Similarity|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4 to form trimethylated histone H4 lysine 20 (H4K20me3) which represents a specific tag for epigenetic transcriptional repression (PubMed:22921934, PubMed:28250819). In association with the NCoR corepressor complex, is involved in the repression of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the formation of H4K20me3 at the gene promoters (PubMed:22921934). Plays an important role in embryonic stem (ES) cell self-renewal and differentiation (PubMed:28951459). Promotes ES cell maintenance by silencing differentiation genes through deposition of H4K20me3 marks (PubMed:28951459). Maintains genome stability of ES cells during differentiation through regulation of heterochromatin formation and repression of endogenous repetitive DNA elements by depositing H4K20me3 marks (PubMed:28250819).|||Interacts with the N-CoR complex (PubMed:22921934). Interacts with EHMT2 and CBX5 (PubMed:28250819).|||Up-regulated by retinoic acid treatment in embryonic carcinoma cells. Present at low levels in untreated cells. http://togogenome.org/gene/10090:Mpc2 ^@ http://purl.uniprot.org/uniprot/Q9D023 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.|||Homodimer. Homooligomer. Forms heterodimers with MPC1 and MPC1L. The heterodimer is the more stable and dominant form.|||Mediates the uptake of pyruvate into mitochondria.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gpr165 ^@ http://purl.uniprot.org/uniprot/Q3V3A3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane http://togogenome.org/gene/10090:Rbm10 ^@ http://purl.uniprot.org/uniprot/Q99KG3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Associates with the spliceosome. Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5 (By similarity).|||Not known. Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (By similarity).|||Nucleus|||RBM10 transcripts also code for an alternative open reading frame (alt-ORF) coding for the MINAS-60 (AC P0DW27) protein (Probable). MINAS-60 and RBM10 ORFs are overlapping and are formed by shifting the reading frame (Probable). http://togogenome.org/gene/10090:Wbp1l ^@ http://purl.uniprot.org/uniprot/Q8BGW2 ^@ Miscellaneous|||Subcellular Location Annotation ^@ May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane http://togogenome.org/gene/10090:Tram2 ^@ http://purl.uniprot.org/uniprot/Q924Z5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAM family.|||Interacts with COL1A1 (By similarity). Interacts with SERCA2B.|||Membrane|||Necessary for collagen type I synthesis. May couple the activity of the ER Ca(2+) pump SERCA2B with the activity of the translocon. This coupling may increase the local Ca(2+) concentration at the site of collagen synthesis, and a high Ca(2+) concentration may be necessary for the function of molecular chaperones involved in collagen folding. Required for proper insertion of the first transmembrane helix N-terminus of TM4SF20 into the ER lumen, may act as a ceramide sensor for regulated alternative translocation (RAT). http://togogenome.org/gene/10090:Cfap52 ^@ http://purl.uniprot.org/uniprot/Q5F201 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CFAP52 family.|||Cytoplasm|||Interacts with BRCA2 (By similarity). Interacts with the CCT chaperonin complex (By similarity). Interacts with HSP70 (By similarity). Interacts with AK8 (By similarity). Interacts with CFAP45 (By similarity). Interacts with DNAI1 (By similarity). Interacts with IQDC (By similarity).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme (By similarity). Important for proper ciliary and flagellar beating. May act in cooperation with CFAP45 and axonemal dynein subunit DNAH11. May play a role in cell growth and/or survival (By similarity).|||cilium axoneme|||flagellum http://togogenome.org/gene/10090:Rabl3 ^@ http://purl.uniprot.org/uniprot/Q9D4V7 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Embryonic lethal.|||Homodimer (PubMed:32220963). Interacts with GPR89; the interaction stabilizes GPR89 (PubMed:32220963). Interacts with RAP1GDS1 (By similarity).|||Required for KRAS signaling regulation and modulation of cell proliferation (PubMed:31406347). Regulator of KRAS prenylation, and probably prenylation of other small GTPases (By similarity). Required for lymphocyte development and function (PubMed:32220963). Not required for myeloid cell development (PubMed:32220963). http://togogenome.org/gene/10090:Sil1 ^@ http://purl.uniprot.org/uniprot/Q9EPK6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SIL1 family.|||Endoplasmic reticulum lumen|||Expressed in several areas of the brain including the cerebellum, cerebral cortex, cortical neurons, glial cells of white matter, hippocampus, olfactory bulb, Purkinje cells, inferior olive and the choroids plexus. Also expressed in the eye and skeletal muscle.|||Expressed in the developing retina and epithelial cells of the lens at 12.5 dpc. Expressed in the developing cerebral cortex at 15.5 dpc.|||Interacts with HSPA5.|||Mice develop adult-onset ataxia with cerebellar Purkinje cell loss. Affected cells have intracellular protein accumulations in the endoplasmic reticulum and the nucleus.|||N-glycosylated.|||Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5.|||Ubiquitinated by the CRL2(FEM1A) and CRL2(FEM1C) complexes, which recognize the -Lys-Xaa-Xaa-Arg C-degron at the C-terminus, leading to its degradation. http://togogenome.org/gene/10090:Mamdc4 ^@ http://purl.uniprot.org/uniprot/D3YY20 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Pgm1 ^@ http://purl.uniprot.org/uniprot/Q3U6X6|||http://purl.uniprot.org/uniprot/Q9D0F9 ^@ Caution|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphohexose mutase family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Monomer.|||Phosphorylation at Thr-467 by PAK1 significantly enhances enzymatic activity.|||There is a known reversal of the Pgm1 and Pgm2 nomenclature applied to mouse versus other vertebrates. The official name of this gene in mouse is Pgm2 but it is the ortholog of other vertebrate PGM1 genes.|||This enzyme participates in both the breakdown and synthesis of glucose. http://togogenome.org/gene/10090:Atg101 ^@ http://purl.uniprot.org/uniprot/Q9D8Z6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophagy factor required for autophagosome formation. Stabilizes ATG13, protecting it from proteasomal degradation.|||Belongs to the ATG101 family.|||Cytoplasm|||Interacts with ATG13. Associates with a complex composed of ATG13, ULK1 and RB1CC1; the association with this complex requires the presence of ATG13.|||Preautophagosomal structure http://togogenome.org/gene/10090:Nfe2l2 ^@ http://purl.uniprot.org/uniprot/Q60795 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-588 and Lys-591 increases nuclear localization whereas deacetylation by SIRT1 enhances cytoplasmic presence.|||Belongs to the bZIP family. CNC subfamily.|||Glycation impairs transcription factor activity by preventing heterodimerization with small Maf proteins (PubMed:31398338). Deglycation by FN3K restores activity (PubMed:31398338).|||Heterodimer; heterodimerizes with small Maf proteins (PubMed:9240432). Interacts (via the bZIP domain) with MAFG and MAFK; required for binding to antioxidant response elements (AREs) on DNA (PubMed:9240432, PubMed:31398338). Interacts with KEAP1; the interaction is direct and promotes ubiquitination by the BCR(KEAP1) E3 ubiquitin ligase complex (PubMed:9887101, PubMed:15282312, PubMed:15367669, PubMed:15581590, PubMed:16790436, PubMed:16581765, PubMed:16507366). Forms a ternary complex with PGAM5 and KEAP1 (By similarity). Interacts with EEF1D at heat shock promoter elements (HSE) (By similarity). Interacts via its leucine-zipper domain with the coiled-coil domain of PMF1 (PubMed:11583586). Interacts with CHD6; involved in activation of the transcription (By similarity). Interacts with ESRRB; represses NFE2L2 transcriptional activity (PubMed:17920186). Interacts with MOTS-c, a peptide produced by the mitochondrially encoded 12S rRNA MT-RNR1; the interaction occurs in the nucleus following metabolic stress (By similarity).|||Mice are viable and fertile but have low and uninducible phase 2 detoxifying enzymes, are much more susceptible to carcinogens and the toxicity of oxygen and electrophiles and cannot be protected by inducers (PubMed:9240432, PubMed:11248092, PubMed:12032331). Mutant mice show an increased mortality during LPS and cecal ligation and puncture-induced septic shock compared to wild-types. They show greater pulmonary inflammation and greater TNF secretion upon LPS administration (PubMed:16585964). Mice lacking both Nfe2l2/Nrf2 and Keap1 reverse the hyperkeratosis phenotype observed in Keap1 knockout: mice and are healthy and viable in normal conditions (PubMed:14517554). Mice lacking both Nfe2l1 and Nfe2l2 die early between embryonic days 9 and 10 and exhibit extensive apoptosis due to marked oxidative stress in cells that is indicated by elevated intracellular reactive oxygen species levels and cell death (PubMed:12968018).|||Nucleus|||Phosphorylation of Ser-40 by PKC in response to oxidative stress dissociates NFE2L2 from its cytoplasmic inhibitor KEAP1, promoting its translocation into the nucleus.|||The ETGE motif, and to a lower extent the DLG motif, mediate interaction with KEAP1.|||Transcription factor that plays a key role in the response to oxidative stress: binds to antioxidant response (ARE) elements present in the promoter region of many cytoprotective genes, such as phase 2 detoxifying enzymes, and promotes their expression, thereby neutralizing reactive electrophiles (PubMed:9240432, PubMed:9887101, PubMed:12032331, PubMed:14517554, PubMed:31398338). In normal conditions, ubiquitinated and degraded in the cytoplasm by the BCR(KEAP1) complex (PubMed:15282312, PubMed:15367669, PubMed:15581590). In response to oxidative stress, electrophile metabolites inhibit activity of the BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2, heterodimerization with one of the small Maf proteins and binding to ARE elements of cytoprotective target genes (PubMed:12032331). The NFE2L2/NRF2 pathway is also activated in response to selective autophagy: autophagy promotes interaction between KEAP1 and SQSTM1/p62 and subsequent inactivation of the BCR(KEAP1) complex, leading to NFE2L2/NRF2 nuclear accumulation and expression of cytoprotective genes (PubMed:20421418, PubMed:20173742). May also be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region (By similarity). Also plays an important role in the regulation of the innate immune response. It is a critical regulator of the innate immune response and survival during sepsis by maintaining redox homeostasis and restraint of the dysregulation of pro-inflammatory signaling pathways like MyD88-dependent and -independent and TNF-alpha signaling (PubMed:16585964). Suppresses macrophage inflammatory response by blocking pro-inflammatory cytokine transcription and the induction of IL6 (PubMed:27211851). Binds to the proximity of pro-inflammatory genes in macrophages and inhibits RNA Pol II recruitment. The inhibition is independent of the Nrf2-binding motif and reactive oxygen species level (PubMed:27211851). Represses antiviral cytosolic DNA sensing by suppressing the expression of the adapter protein STING1 and decreasing responsiveness to STING1 agonists while increasing susceptibility to infection with DNA viruses (By similarity).|||Ubiquitinated in the cytoplasm by the BCR(KEAP1) E3 ubiquitin ligase complex leading to its degradation (PubMed:15282312, PubMed:15367669, PubMed:15581590, PubMed:16790436, PubMed:20421418). In response to oxidative stress, electrophile metabolites, such as sulforaphane, modify KEAP1, leading to inhibit activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and activity (PubMed:15367669). In response to autophagy, the BCR(KEAP1) complex is inactivated (PubMed:20421418).|||Widely expressed. Highest expression in liver, skeletal muscle, luminal cells of the stomach and intestine, lining of the bronchi and alveoli, and in renal tubules; followed by heart, spleen, testis and brain.|||cytosol http://togogenome.org/gene/10090:Arc ^@ http://purl.uniprot.org/uniprot/Q9WV31 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arc expression is regulated at transcription, post-transcription and translation levels (PubMed:19116276, PubMed:24094104). Expression is induced by neuronal and synaptic activity (PubMed:19116276, PubMed:24094104).|||Belongs to the ARC/ARG3.1 family.|||Early endosome membrane|||Expressed in brain and testis (PubMed:12493697). In primary visual cortex, detected in all cortical layers with the exception of layer 5: present at highest level in layers 2/3 and 4, the predominant sites of ocular dominance plasticity (at protein level) (PubMed:20228806). Also expressed in skin-migratory dendritic cells (PubMed:28783680).|||Extracellular vesicle membrane|||Genetic disruption of the protein-coding gene was initially reported to cause early embryonic lethality (PubMed:10727859). However, only a partial deletion of the coding region was performed, leading to dominant-negative effects (PubMed:10727859). A complete deletion of the coding region later showed that mice are viable and display deficits in several forms of long-term memory formation (PubMed:17088210).|||Homooligomer; homooligomerizes into virion-like capsids (PubMed:31151856). Interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2/DYN2 (By similarity). Interacts with CAMK2B (in the kinase inactive state); leading to target ARC to inactive synapses (By similarity). Interacts with PSEN1 (PubMed:22036569). Interacts with GRIN2A and GRIN2B; inhibiting homooligomerization (By similarity).|||Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system (By similarity). ARC protein is released from neurons in extracellular vesicles that mediate the transfer of ARC mRNA into new target cells, where ARC mRNA can undergo activity-dependent translation (By similarity). ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons (By similarity). Acts as a key regulator of synaptic plasticity: required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) and for the formation of long-term memory (PubMed:29264923, PubMed:24094104, PubMed:31151856). Regulates synaptic plasticity by promoting endocytosis of AMPA receptors (AMPARs) in response to synaptic activity: this endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thereby contributing to neuronal homeostasis (PubMed:17088213, PubMed:20211139, PubMed:20228806). Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses (PubMed:23791196). Accumulates at weaker synapses, probably to prevent their undesired enhancement (By similarity). This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material (By similarity). Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory (PubMed:17088210, PubMed:20228806). Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1 (PubMed:22036569). In addition to its role in synapses, also involved in the regulation of the immune system: specifically expressed in skin-migratory dendritic cells and regulates fast dendritic cell migration, thereby regulating T-cell activation (PubMed:28783680).|||Mice show deficits in several forms of long-term memory formation including spatial and fear-related learning, conditioned taste aversion as well as long-term object recognition (PubMed:17088210). They show enhanced early-phase but impaired late-phase long-term potentiation (LTP) as well as impaired long-term depression (LTD). Neurons lacking Arc show an increase in surface levels of AMPA receptors (PubMed:17088210). In the visual cortex, mice are impervious to the effects of deprivation or experience: mice do not exhibit depression of deprived-eye responses or a shift in ocular dominance after brief monocular deprivation (PubMed:20228806). Although mice exhibit normal visual acuity, baseline ocular dominance is abnormal and resemble that observed after dark-rearing (PubMed:20228806). Mice also show schizophrenia-related phenotypes characterized by deficits in sensorimotor gating, cognitive functions, social behaviors and amphetamine-induced psychomotor responses (PubMed:27524619). Divergent alterations between the prefrontal cortex and striatal dopaminergic system that capture aspects of schizophrenia-related neuropathophysiology are observed (PubMed:27524619). Knockout mice show a relative loss of high-frequency electroencephalogram activity in hippocampus, as well as a decrease in phase locking of spikes to electroencephalogram oscillations (PubMed:27038743).|||Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer.|||Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization into virion-like capsids by disrupting an interaction surface essential for high-order oligomerization (PubMed:31151856). Phosphorylation by CaMK2 inhibits synaptic activity (PubMed:31151856).|||Postsynaptic cell membrane|||Postsynaptic density|||Synapse|||Ubiquitinated by UBE3A, leading to its degradation by the proteasome, thereby promoting AMPA receptors (AMPARs) expression at synapses (PubMed:20211139). Ubiquitinated by RNF216 at Lys-268 and Lys-269 limiting ARC protein levels induced by synaptic activity and thus regulating ARC-dependent forms of synaptic plasticity (By similarity).|||Ubiquitously expressed in early mouse embryos (PubMed:10727859). Detectable in brain from postnatal week 1, in testis from postnatal week 3.|||Widely used as activity-dependent neuronal marker to identify recently activated neurons in behavioral studies.|||acrosome|||cell cortex|||clathrin-coated vesicle membrane|||cytoskeleton|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Fam229b ^@ http://purl.uniprot.org/uniprot/B2RVF6|||http://purl.uniprot.org/uniprot/Q8CF36 ^@ Similarity ^@ Belongs to the FAM229 family. http://togogenome.org/gene/10090:Pard6a ^@ http://purl.uniprot.org/uniprot/Q3TY70|||http://purl.uniprot.org/uniprot/Q9Z101 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in the formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:15761148). Regulates centrosome organization and function. Essential for the centrosomal recruitment of key proteins that control centrosomal microtubule organization (By similarity).|||Belongs to the PAR6 family.|||Cell membrane|||Cytoplasm|||Interacts with ECT2 ('Thr-359' phosphorylated form) and PRKCI. Interacts with PALS1 and CRB3 (By similarity). Interacts with PARD3. Interacts with GTP-bound forms of CDC42, RHOQ/TC10 and RAC1. Interacts with the N-terminal part of PRKCI and PRKCZ. Part of a complex with PARD3, CDC42 or RAC1 and PRKCI or PRKCZ. Part of a complex with LLGL1 and PRKCI. Interacts with MAP2K5. Interacts with TGFBR1; involved in TGF-beta induced epithelial to mesenchymal transition. Interacts with DCTN1 and PCM1 (By similarity).|||Phosphorylated by the TGF-beta receptor.|||The PB1 domain mediates interactions with MAP2K5.|||The PDZ domain mediates the interaction with CRB3.|||The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases.|||centriolar satellite|||centrosome|||tight junction http://togogenome.org/gene/10090:Scimp ^@ http://purl.uniprot.org/uniprot/Q3UU41 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in peripheral blood leukocytes (PBLs) (at protein level) (PubMed:21930792). Expressed in dendritic cells, splenocytes and B cells (at protein level) (PubMed:27288407). Strongly expressed in the spleen and lymph nodes and weakly in other tissues of the immune system, including bone marrow, peripheral blood leukocytes (PBLs) and thymus (PubMed:21930792). Not detected in the majority of nonimmune tissues, with the exception of lung (PubMed:21930792). Expressed in antigen-presenting cells (PubMed:21930792). Expressed in macrophages (PubMed:28098138).|||Induced in bone marrow-derived macrophages by CSF2 and particulate beta-glucan.|||Interacts with CD37, CD53 and CD81 (By similarity). Interacts (via proline-rich region) with LYN (via SH3 domain) (PubMed:28098138). Interacts with CSK (via SH2 domain); this interaction is dependent on phosphorylation of Tyr-96 (PubMed:28290451). Interacts with BLNK (via SH2 domain); this interaction is dependent on phosphorylation of Tyr-120 (PubMed:21930792, PubMed:28290451). Interacts with GRB2 (via SH2 domain); this interaction may be dependent on phosphorylation of Tyr-58 (PubMed:21930792, PubMed:28098138). Interacts with TLR4; this interaction occurs upon lipopolysaccharide activation of TLR4 and is enhanced by phosphorylation of Tyr-96 by LYN (PubMed:28098138). This interaction facilitates the phosphorylation of TLR4 by LYN which elicits a selective cytokine response in macrophages (PubMed:28098138).|||Lipid tetraspanin-associated transmembrane adapter/mediator that acts as a scaffold for Src-family kinases and other signaling proteins in immune cells (PubMed:27288407, PubMed:28290451, PubMed:28098138). It is involved in major histocompatibility complex class II (MHC-II) signaling transduction in B cells, where it is required in generating the calcium response and enhancing ERK activity upon MHC-II stimulation (By similarity). In dendritic cells, it is involved in sustaining CLEC7A/DECTIN1 signaling after CLEC7A activation by fungal beta-glucans (PubMed:27288407). It also acts as an agonist-inducible signaling adapter for TLR1, TLR2, TLR3, TLR4, and TLR7 by selectively enabling the expression of pro-inflammatory cytokines IL6 and IL12B in macrophages and acting as a scaffold for phosphorylation of Toll-like receptors by Src-family kinases (PubMed:28098138).|||Mice exhibit no difference in leukocyte development and subset representation in lymphoid organs (PubMed:27288407). No effect on B cell mediated activation of antigen-specific T cells and MHCII glycoprotein downstream signaling in B cells (PubMed:27288407). In dendritic cells, mutants show decreased cytokine production beyond 24 hours after stimulation of CLEC7A signaling (PubMed:27288407).|||Palmitoylated.|||Phosphorylated by the Src-family protein tyrosine kinases LYN and SRC (PubMed:27288407). Phosphorylation occurs on tyrosine residues upon MHC-II stimulation (PubMed:21930792, PubMed:27288407). Phosphorylation also occurs on tyrosine residues after activation of CLEC7A/DECTIN1 by particulate beta-glucan (PubMed:27288407). Lipopolysaccharide (LPS) induces phosphorylation of Tyr-58, Tyr-96 and Tyr-120 differentially to allow temporal recruitment of effector proteins GRB2, CSK and BLNK (PubMed:28290451). Phosphorylation of Tyr-58 is immediately induced by LPS stimulation and allows GRB2 to bind (PubMed:28290451). Tyr-96 is phosphorylated 5 minutes after LPS stimulation, which then allows CSK to bind, followed by phosphorylation of Tyr-120 10 minutes after LPS induction, which allows BLNK to bind (PubMed:28290451). Phosphorylation at Tyr-96 by LYN occurs after activation of TLR4 by LPS; phosphorylation enhances binding to TLR4 (PubMed:28098138, PubMed:28290451).|||filopodium|||phagosome|||ruffle http://togogenome.org/gene/10090:Unc5b ^@ http://purl.uniprot.org/uniprot/Q8K1S3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the unc-5 family.|||Cell membrane|||Complete embryonic lethality, due to defects in blood vessel development that lead to heart failure. Mutant embryos display increased branching of the internal carotid artery and of blood vessels in the nervous system, including thinner and more highly branched brain capillaries. Endothelial tip cells present an increased number of filopodia.|||Highly expressed in brain. Expressed in lung during late development. Expressed during early blood vessel formation, in the semicircular canal and in a dorsal to ventral gradient in the retina.|||Interacts with the cytoplasmic part of DCC (By similarity). Interacts with GNAI2 via its cytoplasmic part. Interacts (via death domain) with DAPK1 (via death domain) (By similarity). Interacts (via extracellular domain) with FLRT2 and FLRT3 (via extracellular domain), but has higher affinity for FLRT3 (PubMed:19492039, PubMed:21673655, PubMed:22405201, PubMed:25374360). Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (By similarity).|||Membrane raft|||Palmitoylation is required for pro-apoptotic activity, but not for location at lipid rafts.|||Phosphorylated on cytoplasmic tyrosine residues.|||Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis.|||Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Functions as netrin receptor that negatively regulates vascular branching during angiogenesis (PubMed:15510105). Mediates retraction of tip cell filopodia on endothelial growth cones in response to netrin (PubMed:15510105). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity). http://togogenome.org/gene/10090:Gm5431 ^@ http://purl.uniprot.org/uniprot/A6PWD6|||http://purl.uniprot.org/uniprot/Q3TMS7 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Rrp9 ^@ http://purl.uniprot.org/uniprot/Q91WM3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-12 and Lys-25 by KAT2B/PCAF under stress impairs pre-rRNA processing. Deacetylation by SIRT7 enhances RRP9-binding to U3 snoRNA, which is a prerequisite for pre-rRNA processing.|||Belongs to the WD repeat RRP9 family.|||Component of a nucleolar small nuclear ribonucleoprotein particle (snoRNP) thought to participate in the processing and modification of pre-ribosomal RNA (pre-rRNA). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Interacts specifically with the U3 small nucleolar RNA (U3 snoRNA). Binds a sub-fragment of the U3 snoRNA surrounding the B/C motif (3UBC). This association with the U3BC RNA is dependent on the binding of a protein called 15.5K to the box B/C motif. The association of the protein with the U3BC RNA was found to be also dependent on a conserved RNA structure that flanks the box B/C motif. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||The WD domains are required for nucleolar localization and U3 small nucleolar RNAs binding.|||nucleolus http://togogenome.org/gene/10090:Nufip2 ^@ http://purl.uniprot.org/uniprot/Q5F2E7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds RNA.|||Cytoplasm|||Interacts with FMR1 (via N-terminus) (PubMed:12837692). Interacts with DDX6 (By similarity).|||Nucleus|||Stress granule http://togogenome.org/gene/10090:P4ha3 ^@ http://purl.uniprot.org/uniprot/H7BX23 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the P4HA family.|||Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.|||Endoplasmic reticulum lumen http://togogenome.org/gene/10090:Rpl14 ^@ http://purl.uniprot.org/uniprot/Q9CR57 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL14 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Gpr155 ^@ http://purl.uniprot.org/uniprot/A2AWR3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cholesterol-binding protein that acts as a regulator of mTORC1 signaling pathway (By similarity). Acts as a sensor of cholesterol to signal cholesterol sufficiency to mTORC1: in presence of cholesterol, binds cholesterol, leading to disrupt interaction between the GATOR1 and KICSTOR complexes and promote mTORC1 signaling (By similarity). Upon cholesterol starvation, GPR155/LYCHOS is unable to perturb the association between GATOR1 and KICSTOR, leading to mTORC1 signaling inhibition (By similarity).|||Interacts with the GATOR1 complex; preventing interaction between GATOR1 and KICSTOR; interaction is disrupted upon cholesterol starvation.|||Lysosome membrane|||Widely expressed in adult tissues and during development (PubMed:20537985). In brain, widely distributed in forebrain regions, while it shows a more restricted distribution in the midbrain and hindbrain regions (PubMed:20537985). Expressed at highest level in the lateral part of striatum and hippocampus (PubMed:20537985). http://togogenome.org/gene/10090:Or7g33 ^@ http://purl.uniprot.org/uniprot/Q8VGG6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gjc2 ^@ http://purl.uniprot.org/uniprot/Q8BQU6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins. Interacts with TJP1.|||Belongs to the connexin family. Gamma-type subfamily.|||Cell membrane|||Expression starts after birth in the central nervous system and parallels myelination process.|||It is uncertain whether Met-1 or Met-4 is the initiator.|||Mainly expressed by oligodendrocytes in the central nervous system (at protein level).|||Mice display myelination abnormalities characterized by extracellular vacuolation along nerve fibers. Mice lacking both Gja12 and Gjb1 display a more severe demyelination phenotype associated with oligodendrocyte death. These mice develop action tremors, tonic seizures, sporadic convulsions and loss of consciousness preceding death in the sixth week after birth.|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a role in myelination in central and peripheral nervous systems.|||gap junction http://togogenome.org/gene/10090:Daglb ^@ http://purl.uniprot.org/uniprot/Q91WC9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Cell membrane|||Deficient mice are viable, fertile and display normal physiological behaviors (PubMed:20159446, PubMed:20147530). Levels of 2-AG are reduced by up to 90% in liver (PubMed:20147530). In contrast, brain 2-AG and arachidonic acid (AA) content are unaltered in deficient mice (PubMed:20159446, PubMed:23103940, PubMed:26779719). However one report describes a decreased by up to 50% of 2-AG in the brain (PubMed:20147530). Disruption of Daglb results in depletion of 2-AG, AA, and prostaglandins (PGE2 and PGD2) in microglia and macrophages, and also attenuated pro-inflammatorycytokine (TNF-alpha) signaling in response to lipopolysaccharide stimulation (PubMed:26779719, PubMed:23103940). In contrast, lipid profiles of neurons are not impacted (PubMed:26779719). Endocannabinoid-mediated retrograde synaptic suppression is intact in deficient mice (PubMed:20159446).|||Expressed in liver and immune cells such as macrophages and microglias (PubMed:23103940, PubMed:31991095, PubMed:26779719, PubMed:20147530). In embryonic brains present in axonal tracts, while in adults localizes to dendritic fields, correlating with the developmental change in requirement for 2-AG synthesis from the pre- to the postsynaptic compartment (at protein level) (PubMed:14610053).|||Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172 (PubMed:23103940, PubMed:31991095). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation (By similarity).|||Lipase that catalyzes the hydrolysis of arachidonic acid (AA)-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further cleaved by downstream enzymes to release arachidonic acid (AA) for cyclooxygenase (COX)-mediated eicosanoid production (PubMed:20159446, PubMed:20147530, PubMed:23103940). Preferentially hydrolyzes DAGs at the sn-1 position in a calcium-dependent manner and has negligible activity against other lipids including monoacylglycerols and phospholipids (By similarity). Plays a key role in the regulation of 2-AG and AA pools utilized by COX1/2 to generate lipid mediators of macrophage and microglia inflammatory responses (PubMed:23103940, PubMed:26779719). Functions also as a polyunsaturated fatty acids-specific triacylglycerol lipase in macrophages (PubMed:31991095). Plays an important role to support the metabolic and signaling demands of macrophages (PubMed:31991095, PubMed:23103940). http://togogenome.org/gene/10090:Dynlt1b ^@ http://purl.uniprot.org/uniprot/P51807 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia (By similarity). May also be a accessory component of axonemal dynein. Plays an important role in male germ cell development and function. Candidate for involvement in male sterility.|||Belongs to the dynein light chain Tctex-type family.|||Cytoplasm|||First abundantly expressed at the pachytene stage of meiosis and persists throughout spermatogenesis.|||Golgi apparatus|||High level in testis (germ cell-specific). Expressed in sperm (at protein level). 200-fold lower in liver, brain, heart, spleen, and kidney. Levels in thymus and two embryonal carcinoma cell lines were several-fold higher than this low constitutive level.|||Homodimer (Probable). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. DYNLT1 and DYNLT3 compete for association with dynein IC (DYNC1I1 or DYNC1I2). Self-associates. Interacts with RHO (By similarity). Interacts with DYNC1I1 and DYNC1I2. Interacts with DOC2A, DOC2B and SCN10A. Interacts with PVR. Interacts with SVIL isoform 2. Interacts with GNB1; the interaction occurs in presence of guanine nucleotide-binding protein G(T) subunit gamma; the interaction diminishes the association of DYNLT1 with dynein IC (DYNC1I1 or DYNC1I2). Interacts with GNB2, GNB3 and GNB5; the interactions occur in presence of guanine nucleotide-binding protein G(T) subunit gamma. Interacts with ACVR2B and ARHGEF2 (By similarity). Interacts with DNAI4 (PubMed:30060180).|||Phosphorylated by BMPR2. The phosphorylation status is proposed to regulate the association with the cytoplasmic dynein complex and may have role in cytoplasmic dynein cargo release (By similarity).|||Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling. Involved in the regulation of mitotic spindle orientation.|||spindle http://togogenome.org/gene/10090:Hoxb13 ^@ http://purl.uniprot.org/uniprot/P70321 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Abd-B homeobox family.|||Exhibits both spatial and temporal colinearity within the main body axis. At 12.5 dpc, is detected in hindgut, urogenital tract, spinal cord and tailbud. Not detected in secondary axes such as the limb and the genital tubercule.|||Heterodimer with MEIS1 and MEIS2.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds preferentially to methylated DNA (By similarity). http://togogenome.org/gene/10090:Cabp5 ^@ http://purl.uniprot.org/uniprot/Q9JLK3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in inner and outer plexiform layers of the retina, and retinal bipolar cells (at protein level) (PubMed:17947313, PubMed:18586882, PubMed:22039235). Expressed in the inner hair cells (IHC) of the cochlea (PubMed:17947313, PubMed:18586882).|||Inhibits calcium-dependent inactivation of L-type calcium channel and shifts voltage dependence of activation to more depolarized membrane potentials (PubMed:18586882). Involved in the transmission of light signals (PubMed:18586882). May positively regulate neurotransmitter vesicle endocytosis and exocytosis in a salt-dependent manner (PubMed:22039235). May play a role in the extension and network organization of neurites (PubMed:22039235).|||Interacts with CACNA1C (via C-terminal CDB motif) in a calcium-dependent manner (PubMed:18586882). Interacts with STXBP1 (By similarity). Interacts with MYO6 (By similarity).|||No morphologic changes, but 50% reduction of the sensitivity of retinal ganglion cell light responses. http://togogenome.org/gene/10090:Pam ^@ http://purl.uniprot.org/uniprot/E9Q704|||http://purl.uniprot.org/uniprot/F8VQA4|||http://purl.uniprot.org/uniprot/P97467 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (By similarity). Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monooxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate (By similarity). The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (By similarity). Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (Probable).|||Binds 2 Cu(2+) ions per subunit.|||Binds one Zn(2+) ion per subunit.|||In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family.|||In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.|||Membrane|||Monomer. Interacts with RASSF9.|||PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (By similarity). PAL activity is stimulated by cadmium and inhibited by mercury (By similarity).|||secretory vesicle membrane http://togogenome.org/gene/10090:Tbcb ^@ http://purl.uniprot.org/uniprot/Q9D1E6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBCB family.|||Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer (By similarity). Involved in regulation of tubulin heterodimer dissociation (PubMed:17184771). May function as a negative regulator of axonal growth (PubMed:17217416).|||Cytoplasm|||In the embryo, expression increases at 12.5 dpc-14.5 dpc. Levels are highest in pre- and postnatal stages which coincide with peaks of cerebral and cerebellar neurogenesis (at protein level).|||Mice display significantly longer axons than wild-type mice. Overexpression of Tbcb causes microtubule depolymerization, growth cone retraction and axonal damage followed by neuronal degeneration.|||Phosphorylation by PAK1 is required for normal function.|||Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state (By similarity). Cofactors B and E can form a heterodimer which binds to alpha-tubulin and enhances their ability to dissociate tubulin heterodimers (PubMed:17184771). Interacts with GAN. Interacts with DCTN1 (By similarity).|||Ubiquitinated in the presence of GAN which targets it for degradation by the proteasome.|||Widely expressed with highest levels in brain. Broadly distributed throughout the neonate brain but restricted mainly to ependymary cells in the adult brain where it is concentrated in the cilia.|||cytoskeleton http://togogenome.org/gene/10090:Tceal9 ^@ http://purl.uniprot.org/uniprot/Q9DD24 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TFS-II family. TFA subfamily.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Lrrc8b ^@ http://purl.uniprot.org/uniprot/Q5DU41 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LRRC8 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Heterohexamer. Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309). In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable).|||Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition.|||The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins. http://togogenome.org/gene/10090:Them4 ^@ http://purl.uniprot.org/uniprot/Q3UUI3 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with V-AKT from AKT8 murine leukemia virus.|||Belongs to the THEM4/THEM5 thioesterase family.|||Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a role in mitochondrial fatty acid metabolism (By similarity). Plays a role in the apoptotic process, possibly via its regulation of AKT1 activity (PubMed:19421406).|||Homodimer and homotetramer (By similarity). Interacts with AKT1 in the cytosol (PubMed:11598301).|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||No visible phenotype. Mice have abnormally elongated mitochondria, but mitochondrial function appears to be normal.|||Phosphorylated.|||ruffle membrane http://togogenome.org/gene/10090:Scoc ^@ http://purl.uniprot.org/uniprot/Q78YZ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCOC family.|||Golgi apparatus membrane|||Homodimer. Interacts with ARL1, ARL2 and ARL3. Directly interacts with FEZ1 and UVRAG. The interaction with UVRAG is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1. Interacts with NRBF2.|||Positive regulator of amino acid starvation-induced autophagy.|||cytosol|||trans-Golgi network http://togogenome.org/gene/10090:Or6c68 ^@ http://purl.uniprot.org/uniprot/Q8VEU0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kl ^@ http://purl.uniprot.org/uniprot/O35082 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.|||Cell membrane|||Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 874.|||Homodimer. Interacts with FGF23 and FGFR1.|||Induced by 1,25-dihydroxyvitamin D(3) in kidney. Down-regulated by angiotensin II and up-regulated by statins through modulation of the RhoA pathway in epithelial cells (in vitro). Isoform 1 (but not isoform 2) is up-regulated by thyroid hormone in adipocytes.|||Inhibited by D-saccharic acid 1,4-lactone and taurocholic acid.|||May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 241 and 874, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D. Essential factor for the specific interaction between FGF23 and FGFR1.|||Membrane-bound protein is present in distal renal tubules, inner ear, ependymal cells of brain choroid plexus, elongating spermatids and mature oocytes (at protein level). Soluble peptide is present in serum (100 pM) and cerebrospinal fluid. Expressed strongly in kidney, moderately in brain choroid plexus, and at low levels in pituitary, placenta, skeletal muscle, urinary bladder, aorta, pancreas, testis, ovary, colon, thyroid gland and adipocytes.|||Mice display a syndrome resembling to human aging, with short lifespan, infertility, atherosclerosis, skin atrophy, osteoporosis and emphysema. They have various metabolic abnormalities, including increased insulin sensitivity and decreased insulin production. Mice overexpressing Kl have increased resistance to insulin and IGF1, a lifespan extended of more than 20%, and generate fewer offspring.|||N-glycosylated.|||Not expressed in the embryo. Expressed in the kidney of newborns.|||Predominates over the secreted form by more than 10 times in all tissues examined.|||Secreted|||The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling. http://togogenome.org/gene/10090:LTO1 ^@ http://purl.uniprot.org/uniprot/Q8CH62 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LTO1 family.|||Forms a complex with YAE1. Interacts with PYCR1 and PYCR2.|||Nucleus|||The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery. May be required for biogenesis of the large ribosomal subunit and initiation of translation. May play a role in the regulation of proline metabolism and ROS production. http://togogenome.org/gene/10090:Pnmt ^@ http://purl.uniprot.org/uniprot/P40935|||http://purl.uniprot.org/uniprot/Q0VB50 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.|||Brain (pons and medulla oblongata), adrenal gland, retina and heart.|||Catalyzes the transmethylation of nonepinephrine (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-methionine as the methyl donor (PubMed:17698731). Other substrates include phenylethanolamine, octopamine and normetanephrine (By similarity).|||In knockout (KO) mice, resting cardiovascular function, including blood pressure (BP), heart rate and cardiac output is the same as that in wild-type mice (PubMed:17698731). Significant difference, however, is observed in the BP response to exercise (PubMed:17698731). The relative diastolic wall thickness and the ratio of left ventricular posterior wall thickness (LVPW) to left ventricular internal dimension (LVID) are significantly increased in KO mice (PubMed:17698731). http://togogenome.org/gene/10090:Swi5 ^@ http://purl.uniprot.org/uniprot/E3WH32|||http://purl.uniprot.org/uniprot/Q8K3D3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SWI5/SAE3 family.|||Component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination.|||Component of the SWI5-SFR1 complex. Interacts with RAD51.|||Component of the swi5-sfr1 complex, a complex required for double-strand break repair via homologous recombination.|||Nucleus http://togogenome.org/gene/10090:Phtf1 ^@ http://purl.uniprot.org/uniprot/Q5IBN5|||http://purl.uniprot.org/uniprot/Q80YS3|||http://purl.uniprot.org/uniprot/Q8C2F6|||http://purl.uniprot.org/uniprot/Q9QZ09 ^@ Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Interacts with FEM1B.|||Membrane|||The PHTF domain was initially defined as an atypical homeodomain, suggesting that this protein could act as a transcription regulator (By similarity). However, the protein is not found in the nucleus and mainly localizes in the endoplasmic reticulum membrane, suggesting that it does not act as a transcription factor (By similarity).|||Widely expressed with highest levels in testis.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Hoatz ^@ http://purl.uniprot.org/uniprot/Q80Y73 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HOATZ family.|||Cytoplasm|||Detected as early as postnatal day 15 (P15), and then continually increased during the first 45 days.|||Male mice exhibit severe defects in spermatogenesis, leading to infertility and varying degrees of hydrocephalus. The epididymal ependymal cilia frequently show disorganized axonemes, reducing motility. Mutant testis shown lack of fully developed flagella in the lumen of the seminiferous tubules; the mutant spermatids elongate but do not maintain the axoneme, leading to severe destruction of the flagella. In contrast, the ultrastructures of motile cilia in the tracheal epithelia are intact. The deficient mice do not display laterality defects, polydactyly, polycystic kidney, or other notable abdominal organ abnormalities indicating that the nodal and primary cilia were unaffected.|||Named Hoatz according to the Hydrocephalus and Oligo-Astheno-Terato-Zoospermia phenotype of Hoatz knockout mice.|||Required for motile ciliogenesis and flagellar genesis by mediating the maturation of the glycolytic enzyme ENO4.|||Specifically expressed in tissues with motile cilia and flagella, such as brain ependyma, lung, testis, and oviduct but not in whole brain, liver,kidney, spleen, and eyeball.|||cilium http://togogenome.org/gene/10090:Zfp511 ^@ http://purl.uniprot.org/uniprot/Q6P0X2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:S100a7a ^@ http://purl.uniprot.org/uniprot/Q6S5I3 ^@ Similarity ^@ Belongs to the S-100 family. http://togogenome.org/gene/10090:Or2ag2 ^@ http://purl.uniprot.org/uniprot/Q9EPF8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Acvrl1 ^@ http://purl.uniprot.org/uniprot/Q61288 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Interacts with TSC22D1/TSC-22.|||Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well. http://togogenome.org/gene/10090:Mrgprb4 ^@ http://purl.uniprot.org/uniprot/Q91ZC0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Membrane|||Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Septin5 ^@ http://purl.uniprot.org/uniprot/Q9Z2Q6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Detected at 17 dpc in the brain. Expression increases during postnatal life and reaches a plateau at approximately P10 (at protein level).|||Filament-forming cytoskeletal GTPase (By similarity). Involved in cytokinesis (Potential). May play a role in platelet secretion.|||Mice have a normal life-span and show no apparent abnormalities, including synaptic properties and hippocampal neuron growth. In platelets, hyperresponsive degranulation phenotype.|||Phosphorylated by DYRK1A.|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation (By similarity). Interacts with SEPTIN2 and SEPTIN5. Interaction with SEPTIN4 not detected. In platelets, associated with a complex containing STX4 (By similarity). Interacts with PRKN; this interaction leads to SEPTIN5 ubiquitination and degradation (PubMed:11078524). Interacts with DYRK1A (PubMed:18938227). Interacts with STX1A; in the cerebellar cortex (PubMed:17296554).|||cytoskeleton http://togogenome.org/gene/10090:Lamp5 ^@ http://purl.uniprot.org/uniprot/Q9D387 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LAMP family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Endosome membrane|||Expressed in embryo at 14 dpc.|||Glycosylated.|||Gross morphology and brain structure are normal. Behavioral assays of locomotory activity, exploratory behavior and motor coordination are also normal. However, some subtle behavioral defects are observed: anxiety levels are decreased and animals also show mild defects in odor discrimination. Electrophysiological assays of striatopallidal synapses indicate defects in short-term synaptic plasticity.|||In brain, strongly expressed in the globus pallidus/ventral pallidum complex, the substantia nigra pars reticulata and the entopeduncular nucleus (at protein level) (PubMed:27272053). Expressed in the external plexiform layer of the olfactory bulb (at protein level). May be weakly expressed in neocortex and striatum (at protein level) (PubMed:27272053). Highly expressed in brain; not detected in other tissues tested (PubMed:17215451). Detected in the cingulate cortex, cortical plate and caudate putamen (PubMed:17215451). In neocortex, specifically expressed in neurons of layers II/III and V (PubMed:17215451).|||Plays a role in short-term synaptic plasticity in a subset of GABAergic neurons in the brain.|||Recycling endosome|||dendrite|||growth cone membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Slamf7 ^@ http://purl.uniprot.org/uniprot/Q8BHK6 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ CRACC:CRACC interaction between NK cells and resident Kupffer cells contribute to Poly I:C/D-GalN-induced fulminant hepatitis.|||Expressed in spleen, lymph node, bone marrow and testis. Lower levels detected in thymus. Expressed in NK cells, B-cells, natural killer cells and activated T-cells.|||Interacts (via ITSM phosphorylated on Tyr-302) with SH2D1B, PTPN6/SHP-1, PTPN11/SHP-2, INPP5D/SHIP1, CSK and FYN.|||Membrane|||Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2 (PubMed:19648922). Mediates natural killer (NK) cell activation through a SH2D1A-independent extracellular signal-regulated ERK-mediated pathway (By similarity). Positively regulates NK cell functions by a mechanism dependent on the adapter SH2D1B. In addition to heterotypic NK cells-target cells interactions also homotypic interactions between NK cells may contribute to activation. However, in the absence of SH2D1B, inhibits NK cell function. Acts also inhibitory in T-cells (PubMed:19151721). May play a role in lymphocyte adhesion (By similarity). In LPS-activated monocytes negatively regulates production of pro-inflammatory cytokines (By similarity).|||The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). http://togogenome.org/gene/10090:Anxa4 ^@ http://purl.uniprot.org/uniprot/P97429|||http://purl.uniprot.org/uniprot/S4R1F2 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||Calcium/phospholipid-binding protein which promotes membrane fusion and is involved in exocytosis.|||Seems to bind one calcium ion with high affinity.|||Zymogen granule membrane http://togogenome.org/gene/10090:Gmnc ^@ http://purl.uniprot.org/uniprot/Q3URY2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GEMC1 family.|||Highly phosphorylated by CDK2; stimulates initiation of DNA replication.|||Nucleus|||Regulator of DNA replication. Promotes initiation of chromosomal DNA replication by mediating TOPBP1- and CDK2-dependent recruitment of CDC45L onto replication origins (By similarity). http://togogenome.org/gene/10090:Pdgfrb ^@ http://purl.uniprot.org/uniprot/P05622 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-578, and to a lesser degree, Tyr-580 is important for interaction with SRC. Phosphorylation at Tyr-715 is important for interaction with GRB2. Phosphorylation at Tyr-739 and Tyr-750 is important for interaction with PIK3R1. Phosphorylation at Tyr-750 is important for interaction with NCK1. Phosphorylation at Tyr-770 and Tyr-856 is important for interaction with RASA1/GAP. Phosphorylation at Tyr-856 is important for efficient phosphorylation of PLCG1 and PTPN11, resulting in increased phosphorylation of AKT1, MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and STAM, and in increased cell proliferation. Phosphorylation at Tyr-1008 is important for interaction with PTPN11. Phosphorylation at Tyr-1008 and Tyr-1020 is important for interaction with PLCG1. Dephosphorylated by PTPRJ at Tyr-750, Tyr-856, Tyr-1008 and Tyr-1020 (By similarity). Dephosphorylated by PTPN2 at Tyr-578 and Tyr-1020.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Interacts with homodimeric PDGFB and PDGFD, and with heterodimers formed by PDGFA and PDGFB. May also interact with homodimeric PDGFC. Monomer in the absence of bound ligand. Interaction with homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD, leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts with SH2B2/APS. Interacts directly (tyrosine phosphorylated) with SHB. Interacts (tyrosine phosphorylated) with PIK3R1 and RASA1. Interacts (tyrosine phosphorylated) with CBL. Interacts (tyrosine phosphorylated) with SRC and SRC family kinases. Interacts (tyrosine phosphorylated) with PIK3C2B, maybe indirectly. Interacts (tyrosine phosphorylated) with SHC1, GRB7, GRB10 and NCK1. Interaction with GRB2 is mediated by SHC1. Interacts (via C-terminus) with NHERF1 (By similarity).|||Lysosome lumen|||N-glycosylated.|||No apparent phenotype up to 16 dpc. Lethality late during gestation or at birth, due to widespread bleedings. This is due to a severe shortage of vascular smooth muscle cells and pericytes, especially in the central nervous system, skin, lung and heart. Mutants suffer from hemorrhages, anemia, thrombocytopenia, and show defects in the formation of kidney glomeruli, due to a lack of mesangial cells.|||Present in an inactive conformation in the absence of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization and activation by autophosphorylation on tyrosine residues.|||Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM (By similarity). Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor.|||Ubiquitinated. After autophosphorylation, the receptor is polyubiquitinated, leading to its degradation.|||Weakly expressed in glomerular mesangial cells and interstitial cells. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, increased expression in interstitial cells at day 4 and expression is markedly elevated at day 7 and is maximal at day 14. http://togogenome.org/gene/10090:Armc12 ^@ http://purl.uniprot.org/uniprot/Q80X86 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Essential for male fertility and sperm mitochondrial sheath formation (PubMed:33536340). Required for proper mitochondrial elongation and coiling along the flagellum during the formation of the mitochondrial sheath (PubMed:33536340). Facilitates the growth and aggressiveness of neuroblastoma cells (By similarity). Increases the EZH2 activity and H3K27me3 levels in a RBBP4-dependent manner, and facilitates the enrichment of polycomb repressive complex 2 and H3K27me3 on gene promoters, resulting in transcriptional repression of tumor suppressors affecting the proliferation, invasion, and metastasis of tumor cells (By similarity).|||Expression begins around postnatal day 20, which roughly corresponds to the haploid, round spermatid stage of spermatogenesis.|||Interacts with TBC1D15, TBC1D21, GK2 and IMMT (PubMed:33536340). Interacts with VDAC2 and VDAC3 in a TBC1D21-dependent manner (PubMed:33536340). Interacts (via ARM domains) with RBBP4 (By similarity).|||Male mice are infertile due to reduced sperm motility and abnormal sperm morphology.|||Mitochondrion outer membrane|||Nucleus|||Testis-specific. http://togogenome.org/gene/10090:Ccdc169 ^@ http://purl.uniprot.org/uniprot/Q8BXX9 ^@ Similarity ^@ Belongs to the CCDC169 family. http://togogenome.org/gene/10090:S1pr5 ^@ http://purl.uniprot.org/uniprot/Q91X56 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in 7-day and 17-day embryos, but not in 11-day and 15-day embryos, implying its role in mammalian development. In oligodendrocytes, expressed throughout development from the immature stages to the mature myelin-froming cell.|||Expressed in spleen and brain. In the CNS expression is restricted to oligodendrocytes.|||Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins (By similarity). S1P activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival. S1P activation on O4-positive pre-oligodendrocytes induces process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway. The S1P-induced survival of mature oligodendrocytes is mediated through a pertussis toxin-sensitive, Akt-dependent pathway. S1P activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival. These effects depend on the developmental stage of the cell. http://togogenome.org/gene/10090:Usp17le ^@ http://purl.uniprot.org/uniprot/A0A1B0GS33 ^@ Function|||Similarity ^@ Belongs to the peptidase C19 family.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes. http://togogenome.org/gene/10090:Sltm ^@ http://purl.uniprot.org/uniprot/Q8CH25 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. http://togogenome.org/gene/10090:Or52e7 ^@ http://purl.uniprot.org/uniprot/Q8VGZ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pgm3 ^@ http://purl.uniprot.org/uniprot/Q8BLS4|||http://purl.uniprot.org/uniprot/Q8BWW3|||http://purl.uniprot.org/uniprot/Q9CYR6 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the phosphohexose mutase family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the conversion of GlcNAc-6-P into GlcNAc-1-P during the synthesis of uridine diphosphate/UDP-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways including protein N- and O-glycosylation. http://togogenome.org/gene/10090:Slc25a35 ^@ http://purl.uniprot.org/uniprot/Q5SWT3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrion inner membrane|||Putative antiporter that exchanges dicarboxylates and sulfur oxoanions across the inner membrane of mitochondria. http://togogenome.org/gene/10090:D2hgdh ^@ http://purl.uniprot.org/uniprot/E9QN44|||http://purl.uniprot.org/uniprot/Q8CIM3 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by zinc and cobalt ions.|||Belongs to the FAD-binding oxidoreductase/transferase type 4 family.|||Catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) to alpha-ketoglutarate (By similarity). Also catalyzes the oxidation of other D-2-hydroxyacids, such as D-malate (D-MAL) and D-lactate (D-LAC) (By similarity). Exhibits high activities towards D-2-HG and D-MAL but a very weak activity towards D-LAC (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Cdh17 ^@ http://purl.uniprot.org/uniprot/Q9R100 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. LI-cadherin may have a role in the morphological organization of liver and intestine.|||Cell membrane|||Expression increases in pro- and pre-B-I cells, decreases in large and small pre-B-II cells, and increases again in immature and mature B-cells.|||Highest expression is found in intestine with lower expression in spleen, bone marrow, lung and testis. No expression detected in liver, kidney, heart, brain or skeletal muscle. Expressed in precursor B-cells and myeloid cells.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Tmprss13 ^@ http://purl.uniprot.org/uniprot/E9QPR6 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Swt1 ^@ http://purl.uniprot.org/uniprot/Q9DBQ9 ^@ Similarity ^@ Belongs to the SWT1 family. http://togogenome.org/gene/10090:Hbq1b ^@ http://purl.uniprot.org/uniprot/Q3U0A6 ^@ Similarity ^@ Belongs to the globin family. http://togogenome.org/gene/10090:Rasl10b ^@ http://purl.uniprot.org/uniprot/Q5SSG5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, detected in the developing heart, skeletal myotomes and dorsal portion of the neural tube. At 13.5 and 15.5 dpc, expressed in the heart and neural tissue including the central and peripheral nervous system. In the embryonic brain, expression is restricted to more mature neurons and absent from the progenitor neuronal cells of the ventricular zone. Also present in mature peripheral neurons, such as the neurons of the dorsal root ganglia and the Auerbach's and Meissner's plexi of the intestinal tract.|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Expressed in heart and brain. In the brain, expression restricted to neurons of the cortex, hippocampus and cerebellum. Sparse expression in the brainstem and almost absent in the hypothalamic region. In the heart, expressed in cardiomyocytes. Not detected in interstitial tissue or vascular cells.|||Interacts with CADPS.|||May facilitate the release of atrial natriuretic peptide by cardiomyocytes and hence play a role in the regulation of arterial pressure.|||No obvious phenotype. Mutant mice are viable and fertile. http://togogenome.org/gene/10090:Fam209 ^@ http://purl.uniprot.org/uniprot/A2APA5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detectable at postnatal day 20 when round spermatids begin to appear.|||Interacts with DPY19L2.|||Nucleus inner membrane|||Predominately expressed in testis.|||Required for sperm acrosome biogenesis. http://togogenome.org/gene/10090:Lpin3 ^@ http://purl.uniprot.org/uniprot/Q149B0|||http://purl.uniprot.org/uniprot/Q571G1|||http://purl.uniprot.org/uniprot/Q99PI4 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the lipin family.|||Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif known to be essential for phosphatidate phosphatase activity.|||Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, a motif known to be a transcriptional binding motif.|||Inhibited by N-ethylmaleimide.|||Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis therefore regulates fatty acid metabolism.|||Nucleus|||Significant expression in intestine and other regions of the gastrointestinal tract. http://togogenome.org/gene/10090:Ap3m1 ^@ http://purl.uniprot.org/uniprot/Q9JKC8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2). Interacts with AGAP1. AP-3 associates with the BLOC-1 complex.|||Belongs to the adaptor complexes medium subunit family.|||Cytoplasmic vesicle membrane|||Golgi apparatus|||Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. http://togogenome.org/gene/10090:Cst13 ^@ http://purl.uniprot.org/uniprot/Q80ZN5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Cytoplasm|||Expressed exclusively in testis. Found in spermatagonia, spermatocytes, round spermatids, elongating spermatids and spermatozoa.|||Expressed only in the adult. Levels are low 1 week postpartum, steadily increase 2 to 5 weeks postpartum, are highest at 7 weeks and then drop to back the levels found at 5 weeks.|||May perform a specialized role during sperm development and maturation.|||Secreted http://togogenome.org/gene/10090:Or8k16 ^@ http://purl.uniprot.org/uniprot/Q8VGC7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp5a1 ^@ http://purl.uniprot.org/uniprot/Q03265 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated on lysine residues. BLOC1S1 is required for acetylation (By similarity). Acetylation of Lys-132, Lys-230 and Lys-498 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the ATPase alpha/beta chains family.|||Cell membrane|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c (By similarity). Interacts with ATPAF2. Interacts with HRG; the interaction occurs on the surface of T-cells and alters the cell morphology when associated with concanavalin (in vitro). Interacts with PLG (angiostatin peptide); the interaction inhibits most of the angiogenic properties of angiostatin (By similarity). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). Interacts with BLOC1S1 (By similarity). Interacts with BCL2L1 isoform BCL-X(L); the interaction mediates the association of BCL2L1 isoform BCL-X(L) with the mitochondrial membrane F(1)F(0) ATP synthase and enhances neurons metabolic efficiency (By similarity). Interacts with CLN5 and PPT1 (PubMed:19941651). Interacts with S100A1; this interaction increases F1-ATPase activity (PubMed:17438143). Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (By similarity).|||Mitochondrion inner membrane|||The siderophore enterobactin (Ent) produced by enteric bacteria binds Fe(3+) and helps bacteria scavenge iron ions from the environment. As a consequence, the mammalian siderocalin LCN2 plays an important role in defense against bacterial infections by sequestering iron bound to microbial siderophores. LCN2 can also bind iron bound to endogenous or nutrient-derived iron chelators and plays an important role in cellular iron homeostasis. Enterobactin produced by non-pathogenic E.coli strains can facilitate mitochondrial iron assimilation, suggesting that iron bound to siderophores from non-pathogenic bacteria may contribute to iron absorption by the host. http://togogenome.org/gene/10090:Ddrgk1 ^@ http://purl.uniprot.org/uniprot/Q80WW9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DDRGK1 family.|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Interacts with TRIP4; the interaction with TRIP4 is direct. Interacts (via PCI domain) with UFL1. Interacts with (unphosphorylated) ERN1/IRE1-alpha; interaction is dependent on UFM1 and takes place in response to endoplasmic reticulum stress, regulating ERN1/IRE1-alpha stability. Interacts with NFKBIA. Interacts with CDK5RAP3. Interacts with SOX9.|||Substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy) (By similarity). In response to endoplasmic reticulum stress, promotes recruitment of the E3 UFM1-protein ligase UFL1 to the endoplasmic reticulum membrane: in turn, UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24, promoting reticulophagy of endoplasmic reticulum sheets (By similarity). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis or inflammatory response (PubMed:30701081). Required for TRIP4 ufmylation, thereby regulating nuclear receptors-mediated transcription (PubMed:28263186). May play a role in NF-kappa-B-mediated transcription through regulation of the phosphorylation and the degradation of NFKBIA, the inhibitor of NF-kappa-B (PubMed:28263186). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186).|||The knockout of the gene results in embryonic lethality between 11.5 and 12.5 dpc (PubMed:28263186). Chondrogenic mesenchymal condensation is absent in 12.5 dpc embryos (PubMed:28263186). Conditional deletion in intestinal epithelial cells causes a significant loss of both Paneth and goblet cells in intestine, which in turn results in dysbiotic microbiota and increased susceptibility to experimentally induced colitis (PubMed:30701081).|||Ubiquitinated. Ubiquitination probably triggers proteasomal degradation and is negatively regulated by UFL1, the enzyme involved in the ufmylation of DDRGK1.|||Ubiquitously expressed (PubMed:20228063). Higher expression in pancreatic islets, pancreatic acini and testis (at protein level) (PubMed:21494687). Highly expressed in the intestinal exocrine cells (PubMed:30701081).|||Ufmylated; conjugated to ubiquitin-like protein UFM1, probably at Lys-268 by UFL1 (PubMed:21494687). The relevance of ufmylation is however unclear: as DDRGK1 acts as substrate adapters for ufmylation, it is uncertain whether ufmylation is a collateral effect of ufmylation process or is required to regulate its activity (By similarity). http://togogenome.org/gene/10090:Rpl6 ^@ http://purl.uniprot.org/uniprot/P47911|||http://purl.uniprot.org/uniprot/Q3UCH0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL6 family.|||Component of the large ribosomal subunit (PubMed:36517592). May bind IPO9 with low affinity (PubMed:11823430).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm|||Rough endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Dtna ^@ http://purl.uniprot.org/uniprot/A0A1Y7VL34|||http://purl.uniprot.org/uniprot/Q3UHJ2|||http://purl.uniprot.org/uniprot/Q3UHP1|||http://purl.uniprot.org/uniprot/Q8CFR5|||http://purl.uniprot.org/uniprot/Q9D2N4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dystrophin family. Dystrobrevin subfamily.|||Cell membrane|||Cytoplasm|||Expressed in skeletal muscle, heart, lung and brain. Sarcolemma and neuromuscular junction in skeletal muscle. Isoform 2 is restricted to the neuromuscular junction. Isoforms 5 and 6 are only expressed in muscle.|||Expression of alpha-dystrobrevin is up-regulated during differentiation, with isoforms 2, 5 and 6 expressed earliest and isoform 3 and 4 expressed later.|||Interacts with dystrophin, utrophin and the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2. Isoforms 5 and 6 do not interact with syntrophin. Isoforms 3 and 4 do not interact with utrophin. Binds dystrobrevin binding protein 1. Interacts with MAGEE1.|||Involved in synapse maturation and required for normal muscle function.|||Phosphorylation of isoform 2 on tyrosine kinase substrate domain present in the C-terminus.|||Synapse|||The coiled coil domain mediates the interaction with dystrophin and utrophin. http://togogenome.org/gene/10090:Mtcp1 ^@ http://purl.uniprot.org/uniprot/Q60945 ^@ Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TCL1 family.|||Enhances the phosphorylation and activation of AKT1 and AKT2.|||Interacts with AKT1 and AKT2 (via PH domain). Does not interact with AKT3 (By similarity).|||Not found at a significant level in any tissue.|||Shares a non-coding 5' exon with isoform 1 which is spliced to a different set of 3' exons encoding an unrelated protein. http://togogenome.org/gene/10090:Slc25a4 ^@ http://purl.uniprot.org/uniprot/P48962 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:31618756, PubMed:31341297). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (PubMed:31489369, PubMed:31341297). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (PubMed:31341297). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (PubMed:31341297). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (PubMed:31341297). Probably mediates mitochondrial uncoupling in tissues that do not express UCP1 (PubMed:31341297). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (PubMed:31489369). It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it (PubMed:31489369). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756).|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Highly expressed in heart, skeletal muscle and brain.|||It is unclear if SLC25A4/ANT1 constitutes a pore-forming component of mitochondrial permeability transition pore (mPTP) (PubMed:14749836, PubMed:31489369). Initial reports, based on deletion of Slc25a4/Ant1 and Slc25a5/Ant2, suggested that ADP/ATP translocase rather acts as a regulator of mPTP (PubMed:14749836). However, deletion of all ADP/ATP translocase components (Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4) completely inhibits mPTP, suggesting that ADP/ATP translocase constitutes a pore-forming component of mPTP (PubMed:31489369). Discrepancy between reports may be caused by overexpression of Slc25a31/Ant4 in mice lacking Slc25a4/Ant1 and Slc25a5/Ant2, which compensates for the loss of Slc25a4/Ant1 and Slc25a5/Ant2 (PubMed:31489369).|||Membrane|||Mice display mitochondrial myopathy affecting heart and skeletal muscles (PubMed:9207786). Hindlimb muscles exhibit abundant ragged-red fibers, characteristic of mitochondrial myopathies (PubMed:9207786). Increased mitochondrial activity is observed, reflecting greater mitochondrial content (PubMed:9207786). In addition, mice are exercise intolerant (PubMed:9207786). Mice develop chronic progressive external ophthalmoplegia, but show normal ocular motility (PubMed:16303948). In retina, while abnormalities are observed in extraocular muscles, retinal structure and function are not affected normal (PubMed:20671283). Cells display impaired mitochondrial uncoupling (PubMed:31341297). Cells show impaired autophagy, leading to accumulation of aberrant mitochondria (PubMed:31618756). Mice lacking Slc25a4/Ant1 and Slc25a5/Ant2 in liver still have mitochondrial permeability transition pore (mPTP) activity, although more Ca(2+) is required to activate the mPTP (PubMed:14749836). Deletion of Slc25a4/Ant1, Slc25a5/Ant2 and Slc25a31/Ant4 in liver completely inhibits mPTP (PubMed:31489369). Mice lacking Slc25a4/Ant1, Slc25a5/Ant2, Slc25a31/Ant4 and Ppif lack Ca(2+)-induced mPTP formation (PubMed:31489369).|||Mitochondrion inner membrane|||Monomer (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1 (PubMed:11809823). Interacts with ARL2BP (PubMed:11809823). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (PubMed:31618756).|||The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) (By similarity). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (PubMed:31341297).|||The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.|||Under cell death induction, transglutaminated by TGM2 (PubMed:19644512). Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers (PubMed:19644512).|||Was reported as a homodimer (PubMed:11809823). However, 3D structure data show that it forms a monomer (By similarity). http://togogenome.org/gene/10090:Tbxa2r ^@ http://purl.uniprot.org/uniprot/P30987|||http://purl.uniprot.org/uniprot/Q5FW61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with RPGRIP1L. Interacts with RACK1; the interaction regulates TBXA2R cell surface expression (By similarity).|||Membrane|||Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C and adenylyl cyclase. http://togogenome.org/gene/10090:Vmn1r200 ^@ http://purl.uniprot.org/uniprot/Q8R281 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Shld1 ^@ http://purl.uniprot.org/uniprot/Q9D112 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7. Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus.|||Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection. Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres. http://togogenome.org/gene/10090:Pramel12 ^@ http://purl.uniprot.org/uniprot/Q8CE24 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Tcirg1 ^@ http://purl.uniprot.org/uniprot/Q9JHF5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the V-ATPase 116 kDa subunit family.|||Essential component of the vacuolar proton pump (V-ATPase), a multimeric enzyme that catalyzes the translocation of protons across the membranes. Required for assembly and activity of the V-ATPase.|||Membrane http://togogenome.org/gene/10090:Cnnm4 ^@ http://purl.uniprot.org/uniprot/Q69ZF7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ACDP family.|||Cell membrane|||Cornea, retina, teeth (at protein level). In the retina it is predominantly localized to the outer plexiform layer, inner plexiform layer and ganglion cell layer. In the tooth strongest expression is observed in the cell body of the ameloblasts. Expressed at high levels in the gastrointestinal tract and testis.|||Interacts with COX11.|||Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function.|||Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo. http://togogenome.org/gene/10090:Gab3 ^@ http://purl.uniprot.org/uniprot/Q8BSM5 ^@ PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GAB family.|||Highly expressed in spleen and thymus and weakly in brain, heart, lung, kidney, uterus, and embryonic stem cells. Also expressed in myeloid and macrophage cell lines.|||Interacts with PIK3R/p85, SHP2 and GRAP2/MONA. May interact with Grb2.|||Phosphorylated on tyrosine residue(s) after macrophage colony-stimulating factor (M-CSF) receptor stimulation. http://togogenome.org/gene/10090:Rps25 ^@ http://purl.uniprot.org/uniprot/P62852|||http://purl.uniprot.org/uniprot/Q58EA6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS25 family.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the small ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Ssxb9 ^@ http://purl.uniprot.org/uniprot/A2BI93 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Ms4a18 ^@ http://purl.uniprot.org/uniprot/J3QN01 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Ccdc57 ^@ http://purl.uniprot.org/uniprot/Q6PHN1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CEP63; the interaction is required for their location to proximal end of centrioles. Interacts with microtubules.|||Pleiotropic regulator of centriole duplication, mitosis, and ciliogenesis (PubMed:32402286). Critical interface between centrosome and microtubule-mediated cellular processes. Centriole duplication protein required for recruitment of CEP63, CEP152, and PLK4 to the centrosome. Independent of its centrosomal targeting, localizes to and interacts with microtubules and regulates microtubule nucleation, stability, and mitotic progression (By similarity).|||centriolar satellite|||centriole|||centrosome|||spindle http://togogenome.org/gene/10090:Mctp1 ^@ http://purl.uniprot.org/uniprot/E9PW38 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fam149a ^@ http://purl.uniprot.org/uniprot/Q8CFV2 ^@ Similarity ^@ Belongs to the FAM149 family. http://togogenome.org/gene/10090:Eif4g1 ^@ http://purl.uniprot.org/uniprot/E9Q9E1|||http://purl.uniprot.org/uniprot/Q6NZJ6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic initiation factor 4G family.|||Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome. Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon. Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning. As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation.|||Cytoplasm|||Nucleus|||Phosphorylated at multiple sites in vivo. Phosphorylation at Ser-1187 by PRKCA induces binding to MKNK1.|||Stress granule|||eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E (cap-binding) and EIF4G1/EIF4G3. Interacts with eIF3 complex, mutually exclusive with EIF4A1 or EIF4A2, EIF4E and through its N-terminus with PABPC1. Interacts with EIF4E or with EIF1 (mutually exclusive) through a common binding site. Interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2. Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate EIF4E. Non-phosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA (By similarity). Interacts with EIF4E3 (PubMed:15153109). Interacts with CIRBP and MIF4GD. Interacts with RBM4. Interacts with HNRNPD/AUF1; the interaction requires RNA. Interacts with DDX3X; the interaction requires RNA. Interacts with DAZAP2 (By similarity). http://togogenome.org/gene/10090:Slc39a1 ^@ http://purl.uniprot.org/uniprot/Q9QZ03 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Endoplasmic reticulum membrane|||Found to be developmentally regulated in the skin where it is expressed in the epidermal layer, excluding the dermis, at embryonic day 17.5 dpc but not in 10.5 dpc and 15.5 dpc. In the small intestine found toward the base of the intestinal villi from 17.5 dpc. In the pancreas, expression was detected from 17.5 dpc and no expression was found in the liver. Also expressed in osteoblasts of developing bone from 15.5 dpc.|||Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space.|||Ubiquitous, except in the pancreas (PubMed:10610721, PubMed:14525987). Highest levels seen in kidney, salivary gland and placenta. http://togogenome.org/gene/10090:Aldh3b3 ^@ http://purl.uniprot.org/uniprot/J3QMK6 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Cell membrane|||Expressed in testis, kidney, small intestine, spleen, white adipose tissue, liver and lung.|||Geranylgeranylation is important for membrane localization and enzyme activity.|||Oxidizes medium and long chain aldehydes into non-toxic fatty acids.|||Probable cloning artifact. http://togogenome.org/gene/10090:Barhl1 ^@ http://purl.uniprot.org/uniprot/P63157 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BAR homeobox family.|||Exclusively expressed in restricted domains of the developing central nervous system, in particular the diencephalon and rhombencephalon, where it is expressed in migrating cells giving rise to the cerebellar external granular layer and to specific populations of dorsal sensory interneurons of the spinal cord.|||Nucleus http://togogenome.org/gene/10090:Cox7a1 ^@ http://purl.uniprot.org/uniprot/P56392|||http://purl.uniprot.org/uniprot/Q792A4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIIa family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nt5m ^@ http://purl.uniprot.org/uniprot/Q8VCE6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 5'(3')-deoxyribonucleotidase family.|||Dephosphorylates specifically the 5' and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides, and so protects mitochondrial DNA replication from excess dTTP. Has only marginal activity towards dIMP and dGMP.|||Homodimer.|||Mitochondrion http://togogenome.org/gene/10090:Cdca3 ^@ http://purl.uniprot.org/uniprot/Q99M54 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ F-box-like protein which is required for entry into mitosis. Acts by participating in E3 ligase complexes that mediate the ubiquitination and degradation of WEE1 kinase at G2/M phase (By similarity).|||Interacts with SKP1. Part of a SCF (SKP1-cullin-F-box) protein ligase complex.|||The KEN box is required for the association with the APC/C-Cdh1 complex.|||Ubiquitinated and degraded by the APC/C-Cdh1 complex.|||cytosol http://togogenome.org/gene/10090:Adam33 ^@ http://purl.uniprot.org/uniprot/A2AP51|||http://purl.uniprot.org/uniprot/Q923W9 ^@ Caution|||Cofactor|||Domain|||PTM|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase. http://togogenome.org/gene/10090:Mybbp1a ^@ http://purl.uniprot.org/uniprot/Q3U2W2|||http://purl.uniprot.org/uniprot/Q7TPV4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MYBBP1A family.|||Citrullinated by PADI4.|||Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (By similarity). Binds to and represses JUN and MYB via the leucine zipper regions present in these proteins. Also binds to and represses PPARGC1A: this interaction is abrogated when PPARGC1A is phosphorylated by MAPK1/ERK. Binds to and stimulates transcription by AHR. Binds to KPNA2. Interacts with CLOCK and CRY1.|||Cytoplasm|||May activate or repress transcription via interactions with sequence specific DNA-binding proteins (PubMed:9447996, PubMed:11956195, PubMed:14744933). Repression may be mediated at least in part by histone deacetylase activity (HDAC activity) (PubMed:14744933). Acts as a corepressor and in concert with CRY1, represses the transcription of the core circadian clock component PER2 (PubMed:19129230). Preferentially binds to dimethylated histone H3 'Lys-9' (H3K9me2) on the PER2 promoter (PubMed:19129230). Has a role in rRNA biogenesis together with PWP1 (By similarity).|||Nucleus|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Akap12 ^@ http://purl.uniprot.org/uniprot/B2RRE0|||http://purl.uniprot.org/uniprot/Q9WTQ5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).|||Binds to dimeric RII-alpha regulatory subunit of PKC.|||Isoform 1 is predominantly found in the nervous system. Isoform 3 is testis specific.|||Membrane|||cytoskeleton http://togogenome.org/gene/10090:Rnf19a ^@ http://purl.uniprot.org/uniprot/P50636 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RBR family. RNF19 subfamily.|||E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR.|||Interacts with UBE2L3 and UBE2L6. Also interacts with transcription factor Sp1. Interacts with SNCAIP and CASR (By similarity). Interacts with VCP.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.|||Membrane|||Preferentially expressed in both sexes during gametogenesis.|||centrosome http://togogenome.org/gene/10090:Adk ^@ http://purl.uniprot.org/uniprot/P55264|||http://purl.uniprot.org/uniprot/Q8BMC5 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives.|||Activity is inhibited by 5-iodotubercidin and 5'-amino-5'-deoxyadenosine.|||Belongs to the carbohydrate kinase PfkB family.|||Binds 3 Mg(2+) ions per subunit.|||Catalyzes the phosphorylation of the purine nucleoside adenosine at the 5' position in an ATP-dependent manner. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.|||Cytoplasm|||Major isoform in spleen and in most brain regions, except in the cerebellum, where it is expressed at a similar level to that of isoform 1 (at protein level).|||Major isoform in testis and kidney. Not detected in most brain regions, except in the cerebellum, where it is expressed at a similar level to that of isoform 2 (at protein level).|||Monomer.|||Nucleus|||Widely expressed (PubMed:15317590). Highly expressed in liver, testis, kidney and spleen (at protein level). In brain, expression in most forebrain structures and the cerebellum is higher than in the midbrain and brainstem (at protein level) (PubMed:15317590). http://togogenome.org/gene/10090:H2al2c ^@ http://purl.uniprot.org/uniprot/A9Z055 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Amacr ^@ http://purl.uniprot.org/uniprot/O09174 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CoA-transferase III family.|||Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (By similarity). Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs (By similarity).|||Mitochondrion|||Monomer.|||Peroxisome http://togogenome.org/gene/10090:Klhl9 ^@ http://purl.uniprot.org/uniprot/Q6ZPT1 ^@ Function|||Subunit ^@ Component of the BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL9, KLHL13 and RBX1. Interacts with AURKB (By similarity).|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis (By similarity). http://togogenome.org/gene/10090:Or8k28 ^@ http://purl.uniprot.org/uniprot/A2AK62 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Lmtk3 ^@ http://purl.uniprot.org/uniprot/Q5XJV6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Expressed in brain. Predominantly expressed in cerebral cortex, thalamus, the cerebellum and hippocampal formation (at protein level).|||Golgi apparatus membrane|||Interacts with ESR1 (By similarity). Interacts with AP-2 complex subunit alpha (PubMed:24760852).|||Membrane|||Protein kinase which phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. May also regulate ESR1 levels indirectly via a PKC-AKT-FOXO3 pathway where it decreases the activity of PKC and the phosphorylation of AKT, thereby increasing binding of transcriptional activator FOXO3 to the ESR1 promoter and increasing ESR1 transcription (By similarity). Involved in endocytic trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons (PubMed:24760852).|||Up-regulated during postnatal development, and expressed in adult stage.|||Viable and grossly normal. Mice exhibit prominent behavioral abnormalities, including locomotor hyperactivity, reduced anxiety, and decreased depression-like behavior.|||axon|||dendrite http://togogenome.org/gene/10090:Sgce ^@ http://purl.uniprot.org/uniprot/E9PX46|||http://purl.uniprot.org/uniprot/F6R6P2|||http://purl.uniprot.org/uniprot/F8WGM3|||http://purl.uniprot.org/uniprot/O70258|||http://purl.uniprot.org/uniprot/Q4H437|||http://purl.uniprot.org/uniprot/Q4H438|||http://purl.uniprot.org/uniprot/Q6L8N9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sarcoglycan alpha/epsilon family.|||Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.|||Golgi apparatus|||Identified in all tissues tested. Expression highest in lung and placenta, moderate in brain, heart and skeletal muscle, low in kidney and liver. Also detected in embryo.|||N-glycosylated.|||Ubiquitinated, leading to its degradation by the proteasome.|||cytoskeleton|||dendrite|||sarcolemma http://togogenome.org/gene/10090:Bms1 ^@ http://purl.uniprot.org/uniprot/Q6PGF5 ^@ Subcellular Location Annotation ^@ nucleolus http://togogenome.org/gene/10090:2310079G19Rik ^@ http://purl.uniprot.org/uniprot/Q9D6L6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Ifitm3 ^@ http://purl.uniprot.org/uniprot/Q9CQW9 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 7.25 dpc strong expression is found at the base of the incipient allantois and weak expression in the mesodermal portion of the posterior amnion, and, importantly, the expression did not extend to the allantois. Expression persisted until the late bud stage (7.5 dpc), but gradually faded around the early head fold stage (7.75 dpc). At an earlier stage, only weak expression is seen throughout the epiblast in 6.0 dpc. But around 6.25-6.5 dpc (before gastrulation), marked expression is evident within the most proximal layer of the epiblast that is in intimate contact with the extraembryonic ectoderm. Expression is indeed induced by extraembryonic ectoderm through signaling molecules. During germ cell formation, is expressed in putative PGC ancestors in embryos at 6.5-7.5 dpc. In migrating PGCs, expression is continuous. After the beginning of gastrulation, the expression migrates to the posterior end of the developing primitive streak at the early/mid streak stage and became very intense in the position where PGCs (Primordial germ cells) differentiate from late streak stage onward.|||Belongs to the CD225/Dispanin family.|||By alpha interferon. Induced in pancreas during caerulein-induced pancreatitis. Induced in pancreas under systemic-lipopolysaccharide treatment and in intestine under Salmonella infection.|||Cell membrane|||Early endosome membrane|||Expressed in acinar cell. Predominantly expressed in nascent primordial germ cells, as well as in gonadal germ cells.|||IFN-induced antiviral protein which disrupts intracellular cholesterol homeostasis. Inhibits the entry of viruses to the host cell cytoplasm by preventing viral fusion with cholesterol depleted endosomes. May inactivate new enveloped viruses which buds out of the infected cell, by letting them go out with a cholesterol depleted membrane. Active against multiple viruses, including influenza A virus, SARS coronaviruses (SARS-CoV and SARS-CoV-2), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV), West Nile virus (WNV), human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV) and vesicular stomatitis virus (VSV) (PubMed:33270927). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry, SARS-CoV and SARS-CoV-2 S protein-mediated viral entry and VSV G protein-mediated viral entry (PubMed:33270927). Plays a critical role in the structural stability and function of vacuolar ATPase (v-ATPase). Establishes physical contact with the v-ATPase of endosomes which is critical for proper clathrin localization and is also required for the function of the v-ATPase to lower the pH in phagocytic endosomes thus establishing an antiviral state. In hepatocytes, IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation. IFITM2 and IFITM3 display anti-HCV activity that may complement the anti-HCV activity of IFITM1 by inhibiting the late stages of HCV entry, possibly in a coordinated manner by trapping the virion in the endosomal pathway and targeting it for degradation at the lysosome. Exerts opposing activities on SARS-CoV-2, including amphipathicity-dependent restriction of virus at endosomes and amphipathicity-independent enhancement of infection at the plasma membrane.|||Interacts with ATP6V0B (PubMed:22467717). Interacts with CD81 (PubMed:16395393). Interacts with SPP1; the interaction reduces OPN expression (By similarity). Interacts with BRI3 (By similarity).|||It has been previously shown that mediates migration of early primordial germ cells (PGCs) (PubMed:16326387). But according to PubMed:16326387, have no detectable effects on development of the germ line or on the generation of live young, hence, is not essential for PGC migration.|||Late endosome membrane|||Lysosome membrane|||Phosphorylation at Tyr-20 is required for endosomal and lysosomal location.|||Polyubiquitinated with both 'Lys-48' and 'Lys-63' linkages. Ubiquitination negatively regulates antiviral activity. Lys-24 is the most prevalent ubiquitination site.|||perinuclear region http://togogenome.org/gene/10090:Lamc3 ^@ http://purl.uniprot.org/uniprot/Q9R0B6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.|||Domain IV is globular.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Gamma-3 is a subunit of laminin-12 (laminin-213), laminin-14 (laminin-423) and laminin-15 (laminin-523).|||Strongly expressed in capillaries and arterioles of kidney as well as in interstitial Leydig cells of testis.|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Tmem239 ^@ http://purl.uniprot.org/uniprot/Q9DA47 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Kcnu1 ^@ http://purl.uniprot.org/uniprot/G3X9P7|||http://purl.uniprot.org/uniprot/O54982 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa5.1/KCNU1 sub-subfamily.|||Cell membrane|||Homotetramer; which constitutes the calcium-activated potassium channel. May interact with LRRC52; this interaction may change some channel gating properties, such as shifting gating to more negative potentials at a given pH.|||Membrane|||Mutant males are infertile, but their sperm retains some fertility within in vitro fertilization assays. Spermatozoa exhibit a higher incidence of morphological abnormalities as compared to wild-type, accentuated by hypotonic challenge and deficits in motility, in the absence of bicarbonate.|||Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). Represents the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina.|||Testis-specific. Mainly expressed in spermatocytes.|||The C-terminal cytosolic region confers the pH-dependence.|||The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel.|||The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor.|||The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium (By similarity).|||Very low expression levels in testis before postnatal day 25 (P25). Levels strongly increase between P25 and P30, and then remain high from P30 through P150. http://togogenome.org/gene/10090:Tshb ^@ http://purl.uniprot.org/uniprot/E9Q4F3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycoprotein hormones subunit beta family.|||Secreted http://togogenome.org/gene/10090:Spint4 ^@ http://purl.uniprot.org/uniprot/Q9D263 ^@ Developmental Stage|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By androgens. Expression diminishes after 1-3 days and disappears 7 days postgonadectomy.|||Expression starts at the time of epididymal maturation.|||Highly expressed in the epididymis, in the epithelial cells of the distal caput and early corpus.|||Secreted http://togogenome.org/gene/10090:Pcdha4 ^@ http://purl.uniprot.org/uniprot/O88689 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell (PubMed:27161523). This is an head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin (PubMed:27161523). The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane (PubMed:27161523). Each cadherin domain binds three calcium ions (PubMed:27161523).|||Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination (Probable). Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain (PubMed:27161523).|||Cell membrane|||Detected in brain throughout embryonic development. Detected in adult brain, in particular in cerebellum and forebrain.|||Forms homodimers in trans (molecules expressed by two different cells) (PubMed:27161523). Forms promiscuous heterodimers in cis (at the plasma membrane of the same cell) with other protocadherins (PubMed:27161523). Interacts with FYN (PubMed:9655502).|||The protocadherins alpha are expressed from a single gene cluster similarly to immunoglobulin and T-cell receptors. The N-terminal region containing the 6 extracellular cadherin domains, unique to each protocadherin alpha, is encoded by one of the large exons found in tandem array within the gene cluster. The C-terminal region, identical to all protocadherins alpha, is encoded by 3 shared exons. http://togogenome.org/gene/10090:Slc39a6 ^@ http://purl.uniprot.org/uniprot/Q8C145 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Cleaved on the N-terminus before locating to the plasma membrane.|||Highly expressed in the brain and testis. In the brain strongly expressed in the CA1 and CA3 regions, Purkinje cells in cerebellum and dentate gyrus in hippocampus. In testis found in spermatids or mature sperms in the central areas of seminiferous tubules.|||Highly expressed in the oocyte and egg but decreased and remained low after fertilization (PubMed:25143461). During preimplantation embryos, localizes to the cortex (PubMed:25143461).|||Induced during neuronal differentiation neuroblastoma cells line but down-regulated during myogenic differentiation of skeletal muscle cells line (PubMed:11891044). Induced during epithelialto-mesenchymal transition (EMT) (PubMed:28098160).|||Interacts with SLC39A10; which triggers cells to undergo EMT and mitosis. Found in a complex with SLC39A6, SLC39A10 and with the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (By similarity). Found in a complex with SLC39A6, SLC39A10 and with NCAM1; this complex controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition (EMT) (PubMed:28098160). Found in a complex with SLC39A6, SLC39A10 and with GSK3B that controls NCAM1 phosphorylation (PubMed:28098160).|||Membrane raft|||N-glycosylated.|||Phosphorylated by ZAP70 in response to TCR stimulation leading to its activation.|||Zinc-influx transporter which plays a role in zinc homeostasis and in the induction of epithelial-to-mesenchymal transition (EMT) (PubMed:28098160). When associated with SLC39A10, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial- to-mesenchymal transition (EMT) (By similarity). The SLC39A10-SLC39A6 heterodimer also controls NCAM1 phosphorylation and its integration into focal adhesion complexes during EMT (PubMed:28098160). Zinc influx inactivates GSK3B, enabling unphosphorylated SNAI1 in the nucleus to down-regulate adherence genes such as E-cadherin, causing loss of cell adherence (By similarity). In addition, the SLC39A10-SLC39A6 heterodimer plays an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (By similarity). Participates in the T-cell receptor signaling regulation by mediating cellular zinc uptake into activated lymphocytes (By similarity). Regulates the zinc influx necessary for proper meiotic progression to metaphase II (MII) that allows the oocyte-to-egg transition (PubMed:25143461).|||lamellipodium membrane http://togogenome.org/gene/10090:Or8h9 ^@ http://purl.uniprot.org/uniprot/Q8VG37 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chrnb1 ^@ http://purl.uniprot.org/uniprot/P09690 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-1/CHRNB1 sub-subfamily.|||Cell membrane|||Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Ap1m2 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZX6|||http://purl.uniprot.org/uniprot/A0A0R4J1L4|||http://purl.uniprot.org/uniprot/Q9WVP1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Interacts with P2X4 (By similarity).|||Belongs to the adaptor complexes medium subunit family.|||Golgi apparatus|||Phosphorylation of membrane-bound AP1M1/AP1M2 increases its affinity for sorting signals.|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Ccdc81 ^@ http://purl.uniprot.org/uniprot/Q9D5W4 ^@ Subcellular Location Annotation ^@ centrosome http://togogenome.org/gene/10090:Eif2s3y ^@ http://purl.uniprot.org/uniprot/Q9Z0N2 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.|||Has a homolog on chromosome X (Eif2s3x).|||Knockout males are infertile. Their testes are smaller as compared to wild-type fertile males and exhibit spermatogonial proliferation block.|||Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). Along with its paralog on chromosome X, may contribute to spermatogenesis up to the round spermatid stage (PubMed:11528390, PubMed:25579647, PubMed:26823431).|||Widely expressed. In the adult brain, high levels in hippocampus, habenula, hypothalamic nuclei and cerebellum. Also expressed in embryonic brain.|||eIF2 is an heterotrimer composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (Eif2s3x and Eif2s3y) chain. eIF2 is member of the 43S pre-initiation complex (43S PIC). http://togogenome.org/gene/10090:Ago3 ^@ http://purl.uniprot.org/uniprot/Q8CJF9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the argonaute family. Ago subfamily.|||Interacts with EIF4B, IMP8, PRMT5 and TNRC6B (By similarity). Interacts with APOBEC3F, APOBEC3G and APOBEC3H. Interacts with EDC4 (By similarity).|||P-body|||Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Proposed to be involved in stabilization of small RNA derivates (siRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent siRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4 (PubMed:19174539). Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity (By similarity).|||Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO3 when it is engaged with a TDMD target. http://togogenome.org/gene/10090:Smad6 ^@ http://purl.uniprot.org/uniprot/O35182 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine methylation by PRMT1, which is recruited by BMPR2, initiates BMP-Induced signaling and induces dissociation from the BMPR1B receptor at the cell surface leading to derepress downstream Smad1/Smad5 signaling.|||Belongs to the dwarfin/SMAD family.|||By TGF-beta and BMP4.|||Interacts with NEDD4L. Interacts with WWP1. Interacts with STAMBP and PRKX (By similarity). Interacts with RNF111 and AXIN1. Interacts with TGF-beta type I receptor superfamily members, including ACVR1B, BMPR1B and TGFBR1. In response to BMP2 treatment, interacts with SMAD1; this interaction may inhibit SMAD1-binding to SMAD4. Interacts with HOXC8 and HOXC9 (By similarity). Interacts with PELI1; this interaction interferes with PELI1 complex formation with TRAF6, IRAK1, IRAK4 and MYD88 in response to IL1B and hence negatively regulates IL1R-TLR signaling. Interacts with TSC22D1/TSC-22 (By similarity).|||Monoubiquitinated at Lys-174 by the E2/E3 hybrid ubiquitin-protein ligase UBE2O, leading to reduced binding affinity for the activated BMP type I receptor ACVR1/ALK2, thereby enhancing BMP7 and regulating adipocyte differentiation (By similarity). Ubiquitinated by WWP1 (PubMed:15221015). Ubiquitinated by ARK2C, promoting proteasomal degradation, leading to enhance the BMP-Smad signaling (PubMed:23610558).|||Nucleus|||Phosphorylated by BMP type 1 receptor kinase and by PRKX.|||Transforming growth factor-beta superfamily receptors signaling occurs through the Smad family of intracellular mediators. SMAD6 is an inhibitory Smad (i-Smad) that negatively regulates signaling downstream of type I transforming growth factor-beta (By similarity). Acts as a mediator of TGF-beta and BMP anti-inflammatory activities. Suppresses IL1R-TLR signaling through its direct interaction with PEL1, preventing NF-kappa-B activation, nuclear transport and NF-kappa-B-mediated expression of pro-inflammatory genes (PubMed:16951688). Blocks the BMP-SMAD1 signaling pathway by competing with SMAD4 for receptor-activated SMAD1-binding. Binds to regulatory elements in target promoter regions (By similarity).|||Ubiquitous in various organs, with higher levels in lung. http://togogenome.org/gene/10090:Aldh18a1 ^@ http://purl.uniprot.org/uniprot/Q9Z110 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.|||Homohexamer or homotetramer.|||In the C-terminal section; belongs to the gamma-glutamyl phosphate reductase family.|||In the N-terminal section; belongs to the glutamate 5-kinase family.|||Isoform Short: Inhibited by L-ornithine with a Ki of approximately 0.25 mm. Isoform Long: Insensitive to ornithine inhibition. Thus, the two amino acid insert in the long isoform abolishes feedback inhibition of P5CS activity by L-ornithine.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pard6b ^@ http://purl.uniprot.org/uniprot/Q9JK83 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein involved in asymmetrical cell division and cell polarization processes. Probably involved in formation of epithelial tight junctions. Association with PARD3 may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins.|||Belongs to the PAR6 family.|||Cell membrane|||Cytoplasm|||Expressed in pancreas and in both adult and fetal kidney. Weakly expressed in placenta and lung. Not expressed in other tissues.|||Interacts with PARD3. Interacts with GTP-bound forms of CDC42, RHOQ/TC10 and RAC1. Interacts with the N-terminal part of PRKCI and PRKCZ. Part of a complex with PARD3, CDC42 or RAC1 and PRKCI or PRKCZ. Part of a complex with LLGL1 and PRKCI. Interacts with ALS2CR19. Interacts with ECT2 (By similarity). Interacts with PALS1.|||The PDZ domain mediates the interaction with PALS1.|||The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases.|||tight junction http://togogenome.org/gene/10090:Jmjd4 ^@ http://purl.uniprot.org/uniprot/Q8BFT6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the 2-oxoglutarate and iron-dependent C4-lysyl hydroxylation of ETF1 at 'Lys-63' thereby promoting the translational termination efficiency of ETF1 (By similarity). Not essential for embryonic stem cell (ESC) maintenance and the embryonic and postnatal development (PubMed:27147518).|||Cytoplasm|||Interacts with ETF1 (By similarity). Interacts with the ETF1-GSPT1 complex (By similarity).|||Mice are born at the expected Mendelian rate and are healthy, fertile and physiologically normal (PubMed:27147518). Embryonic stem cells (ESCs) exhibit normal colony morphology and cell proliferation rates and maintain normal expression of pluripotent genes (PubMed:27147518). http://togogenome.org/gene/10090:Plxnd1 ^@ http://purl.uniprot.org/uniprot/Q3UH93 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E. Plays an important role in cell-cell signaling, and in regulating the migration of a wide spectrum of cell types. Regulates the migration of thymocytes in the medulla. Regulates endothelial cell migration. Plays an important role in ensuring the specificity of synapse formation. Mediates anti-angiogenic signaling in response to SEMA3E. Required for normal development of the heart and vasculature.|||Detected in embryonic heart and vascular endothelium, brain, dorsal root ganglia, adrenal gland, lung mesenchyme, small intestine and in the ossification centers of vertebral bodies.|||Interacts with NRP1 and SEMA4A (PubMed:15239958, PubMed:17318185). Interacts with SH3BP1; they dissociate upon SEMA3E binding to PLXND1 allowing SH3BP1 to transduce downstream signal through RAC1 inactivation (By similarity).|||Neonate lethality, due to defects in the development of the heart outflow tract and in aortic arch patterning, plus defects in peripheral vasculature. Mice also display skeletal defects, but these may be caused by defects in the embryonic vasculature.|||lamellipodium membrane http://togogenome.org/gene/10090:Rffl ^@ http://purl.uniprot.org/uniprot/Q148A8|||http://purl.uniprot.org/uniprot/Q3TEV8|||http://purl.uniprot.org/uniprot/Q3UCG9|||http://purl.uniprot.org/uniprot/Q3UD78|||http://purl.uniprot.org/uniprot/Q6ZQM0 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Cell membrane|||E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Also ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate apoptosis downstream of death domain receptors. Also negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling.|||Interacts with CASP8 and CASP10. Interacts with RIPK1 (via protein kinase domain); involved in RIPK1 ubiquitination. Interacts with PRR5L. Interacts (via RING-type zinc finger) with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2.|||No visible phenotype.|||Palmitoylated.|||Recycling endosome membrane|||The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling.|||The RING-type zinc finger is required for the ubiquitination of target proteins.|||Ubiquitous. Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis, thymus, whole embryo and embryonic stem cells.|||Undergoes caspase-mediated cleavage upon death-receptor activation, by TNFSF10 for instance. May be mediated by the caspases CASP8 and CASP10 in a negative feedback loop (By similarity).|||Up-regulation by LPA/lysophosphatidic acid is dependent on GNA12.|||cytosol http://togogenome.org/gene/10090:Egln2 ^@ http://purl.uniprot.org/uniprot/Q91YE2 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Fe(2+) ion per subunit.|||Highly expressed in testis, expression was also detected in the heart brain, liver kidney and lung. Expression was lowest in spleen and skeletal muscle. Constitutively expressed during differentiation of C2C12 skeletal myocytes.|||Interacts with E3 ligase SIAH2. Interacts with LIMD1, WTIP and AJUBA.|||Nucleus|||Null mice exhibit a lowering of oxygen consumption in skeletal muscle. Glucose oxidation is reduced to around 35%. Hypoxia tolerance is induced in myofibers.|||Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A (PubMed:24809345). Target proteins are preferentially recognized via a LXXLAP motif (By similarity). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:18176562, PubMed:19587290, PubMed:21083501). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:18176562, PubMed:19587290, PubMed:21083501). Also hydroxylates HIF2A (PubMed:18176562, PubMed:19587290, PubMed:21083501). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:18176562, PubMed:19587290, PubMed:21083501). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:18176562, PubMed:19587290, PubMed:21083501). Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes (PubMed:18176562, PubMed:19587290, PubMed:21083501). EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PubMed:18176562, PubMed:19587290, PubMed:21083501). Also regulates susceptibility to normoxic oxidative neuronal death (PubMed:18176562, PubMed:19587290, PubMed:21083501). Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation (By similarity). Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (By similarity). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (PubMed:24809345).|||The Beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.|||Ubiquitinated by SIAH1 and/or SIAH2 in response to the unfolded protein response (UPR), leading to its degradation. http://togogenome.org/gene/10090:Kpna2 ^@ http://purl.uniprot.org/uniprot/P52293|||http://purl.uniprot.org/uniprot/Q52L97 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the importin alpha family.|||Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.|||Cytoplasm|||Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.|||Functions in nuclear protein import.|||Heterodimer; with KPNB1 (By similarity). Component of a complex containing CSE1L, RAN and KPNA2 (By similarity). Interacts directly with CSE1L (By similarity). Interacts with PLAG1 (By similarity). Interacts with APEX1 (via N-terminus) (By similarity). Interacts with FRG1 (via N-terminus) (By similarity). Interacts with ARL4A, CTNNBL1 and NBN (By similarity). Interacts with ANP32E (PubMed:10692581). Interacts with SNAI1 (via zinc fingers) (PubMed:21454664). Interacts with SNAI2 (via zinc fingers) (By similarity). Interacts with BAG6 (By similarity). Interacts with AIFM2; this interaction likely mediates the translocation of AIFM2 into the nucleus upon oxidative stress. Interacts with RSL1D1 (By similarity).|||Nucleus|||Slightly detected in brain but not in cerebellum and skeletal muscle, highly expressed in testis and spleen.|||The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins.|||The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding. http://togogenome.org/gene/10090:Ppie ^@ http://purl.uniprot.org/uniprot/Q9QZH3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclophilin-type PPIase family. PPIase E subfamily.|||Identified in the spliceosome C complex. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex. The IB complex does not contain PRPF19. Interacts (via RNA-binding domain) with KMT2A (via the third PHD-type zinc-finger).|||Involved in pre-mRNA splicing as component of the spliceosome. Combines RNA-binding and PPIase activities. Binds mRNA and has a preference for single-stranded RNA molecules with poly-A and poly-U stretches, suggesting it binds to the poly(A)-region in the 3'-UTR of mRNA molecules. Catalyzes the cis-trans isomerization of proline imidic peptide bonds in proteins. Inhibits KMT2A activity; this requires proline isomerase activity.|||Nucleus|||The RRM domain mediates both interaction with RNA and with KMT2A (via the third PHD-type zinc-finger), but has much higher affinity for the KMT2A PHD-type zinc-finger. http://togogenome.org/gene/10090:Wdfy2 ^@ http://purl.uniprot.org/uniprot/Q8BUB4 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts in an adapter protein-like fashion to mediate the interaction between the kinase PRKCZ and its substrate VAMP2 and increases the PRKCZ-dependent phosphorylation of VAMP2 (By similarity). Positively regulates adipocyte differentiation, by facilitating the phosphorylation and thus inactivation of the anti-adipogenetic transcription factor FOXO1 by the kinase AKT1 (PubMed:18388859). Plays a role in endosomal control of AKT2 signaling; required for insulin-stimulated AKT2 phosphorylation and glucose uptake and insulin-stimulated phosphorylation of AKT2 substrates (PubMed:20189988). Participates in transferrin receptor endocytosis (By similarity).|||Cytoplasm|||Early endosome|||Endosome|||Highly expressed in the brain (at protein level).|||Homodimer (By similarity). Interacts (via WD repeats 1-3) with AKT1, AKT2, PRKCZ and PRKCI (PubMed:16792529, PubMed:20189988). Interacts with VAMP2 (PubMed:17313651). Forms a complex with VAMP2 and PRKCZ (PubMed:17313651). Interacts with FOXO1 (PubMed:18388859). Forms a complex with AKT1 and FOXO1 (PubMed:18388859).|||The FYVE-type zinc finger is essential for its vesicular localization.|||Transiently up-regulated during adipogenesis (at protein level). http://togogenome.org/gene/10090:Mpp3 ^@ http://purl.uniprot.org/uniprot/Q6XE40 ^@ Similarity ^@ Belongs to the MAGUK family. http://togogenome.org/gene/10090:Serpina3f ^@ http://purl.uniprot.org/uniprot/Q3UDB3|||http://purl.uniprot.org/uniprot/Q3UTZ5|||http://purl.uniprot.org/uniprot/Q80X76 ^@ Domain|||Miscellaneous|||Similarity ^@ Belongs to the serpin family.|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Ntn5 ^@ http://purl.uniprot.org/uniprot/Q3UQ22 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Deficient mice exhibit ectopic motor neurons that migrate out of the ventral horn and into the motor roots.|||Detected in boundary cap cells at 11.5 dpc, expression is strongest between 15.5 and 17.5 dpc and is barely detectable at birth.|||Plays a role in neurogenesis. Prevents motor neuron cell body migration out of the neural tube.|||Secreted http://togogenome.org/gene/10090:Ocel1 ^@ http://purl.uniprot.org/uniprot/G5E815|||http://purl.uniprot.org/uniprot/Q8VCR9 ^@ Similarity ^@ Belongs to the ELL/occludin family. http://togogenome.org/gene/10090:Or10al2 ^@ http://purl.uniprot.org/uniprot/Q7TRJ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Emd ^@ http://purl.uniprot.org/uniprot/O08579 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early and highly significant depletion of primordial follicles.|||In the ovary, highest expression is seen in primordial follicle oocytes (at protein level) (PubMed:32923640). Detected in embryonic fibroblasts, skeletal muscle, heart muscle and tongue epithelium (at protein level). Widely expressed.|||Interacts with lamins A and C, BANF1, GMCL, BCLAF1 and YTHDC1/YT521. Interacts with TMEM43; the interaction retains emerin in the inner nuclear membrane. Interacts with ACTB, SPTAN1, F-actin, CTNNB1 and beta-tubulin (By similarity). Interacts with SUN1 and SUN2. Interacts with TMEM201. Interacts with NEMP1 (By similarity).|||Nucleus inner membrane|||Nucleus outer membrane|||Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells. http://togogenome.org/gene/10090:Cd59b ^@ http://purl.uniprot.org/uniprot/P58019 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore (By similarity).|||Widely expressed in the kidneys, brain, lungs, spleen and testis (PubMed:11471050) Testis specific (PubMed:10946279). http://togogenome.org/gene/10090:Serpinb9c ^@ http://purl.uniprot.org/uniprot/I7HJI5|||http://purl.uniprot.org/uniprot/Q80WW4|||http://purl.uniprot.org/uniprot/Q9D6A7 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Scnn1a ^@ http://purl.uniprot.org/uniprot/Q3USG4|||http://purl.uniprot.org/uniprot/Q61180 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by WNK1, WNK2, WNK3 and WNK4.|||Apical cell membrane|||Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily.|||Cytoplasm|||Cytoplasmic granule|||ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation.|||Expressed in kidney (at protein level) (PubMed:22207244). Expressed in lung (at protein level) (PubMed:22207244, PubMed:30659401). Expressed in the epididymis (at protein level) (PubMed:30659401). In the caput and corpus regions of the epididymis, expressed uniformly on the luminal and basal surfaces of the ducts and in the sperm in the duct lumen (PubMed:30659401). Also expressed in distal colon and, at low levels, in liver (PubMed:10409305).|||Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (Probable). Interacts with NEDD4 (via WW domains) (PubMed:11244092, PubMed:15123669). Interacts with NEDD4L (via WW domains) (PubMed:11244092, PubMed:12424229, PubMed:15123669). Interacts with WWP1 (via WW domains). Interacts with WWP2 (via WW domains). Interacts with the full-length immature form of PCSK9 (pro-PCSK9).|||Membrane|||N-glycosylated.|||Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception.|||Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation.|||acrosome|||cilium|||flagellum http://togogenome.org/gene/10090:Mak16 ^@ http://purl.uniprot.org/uniprot/Q8BGS0 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MAK16 family.|||May be due to a competing donor splice site.|||nucleolus http://togogenome.org/gene/10090:Patl2 ^@ http://purl.uniprot.org/uniprot/A2ARM1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PAT1 family.|||Cytoplasm|||Interacts with LSM1.|||Nucleus|||RNA-binding protein that acts as a translational repressor. http://togogenome.org/gene/10090:Frmd4b ^@ http://purl.uniprot.org/uniprot/Q920B0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with CYTH3 (PubMed:11445584, PubMed:20080746). Interacts with PARD3 (PubMed:20080746). Interacts with CYTH1.|||Isoform 1 is expressed in the brain. Isoform 2 is expressed in the lung (at protein level).|||Member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling. May function as a scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (PubMed:20080746). Plays a redundant role with FRMD4A in epithelial polarization (PubMed:20080746).|||adherens junction|||cytoskeleton|||tight junction http://togogenome.org/gene/10090:Susd6 ^@ http://purl.uniprot.org/uniprot/Q8BGE4|||http://purl.uniprot.org/uniprot/Q8C0M5 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||May play a role in growth-suppressive activity and cell death. May be involved in the production of chemokine molecules in umbilical vein endothelial cells (HUVECs) cultured in THP1 monocyte LPS-induced medium (By similarity). Plays a role in preventing tumor onset (PubMed:24652652).|||Membrane|||Mice are viable and fertile and do not show any notable developmental defect or spontaneous tumor development within 2 years. SUSD6 and TP53 double knockout mice show an increase in tumor development and a decrease in lifespan compared to TP53 knockout mice carrying wild-type SUSD6 (PubMed:24652652). http://togogenome.org/gene/10090:Tmod3 ^@ http://purl.uniprot.org/uniprot/Q3TFA9|||http://purl.uniprot.org/uniprot/Q9JHJ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tropomodulin family.|||Binds to the N-terminus of tropomyosin and to actin.|||Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity).|||Ubiquitous.|||cytoskeleton http://togogenome.org/gene/10090:Gtf3c1 ^@ http://purl.uniprot.org/uniprot/Q8K284 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIIC subunit 1 family.|||Incomplete sequence.|||Nucleus|||Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with IGHMBP2. Interacts with MAF1.|||Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element (By similarity). http://togogenome.org/gene/10090:Pcdhb18 ^@ http://purl.uniprot.org/uniprot/Q91Y02 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Potential calcium-dependent cell-adhesion protein. http://togogenome.org/gene/10090:Mrps10 ^@ http://purl.uniprot.org/uniprot/E9QJS0|||http://purl.uniprot.org/uniprot/G5E8U5|||http://purl.uniprot.org/uniprot/G5E8U8|||http://purl.uniprot.org/uniprot/Q501J4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the universal ribosomal protein uS10 family.|||Mitochondrion http://togogenome.org/gene/10090:Aebp2 ^@ http://purl.uniprot.org/uniprot/Q9Z248 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an accessory subunit for the core Polycomb repressive complex 2 (PRC2), which mediates histone H3K27 (H3K27me3) trimethylation on chromatin leading to transcriptional repression of the affected target gene. Plays a role in nucleosome localization of the PRC2 complex.|||Belongs to the AEBP2/jing C2H2-type zinc-finger family.|||Expressed in brain, brown adipose tissue, white adipose tissue, heart, kidney, lung, skeletal muscle, small intestine and spleen. Expressed at low levels in liver.|||Nucleus|||Self-associates (By similarity). Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:19026780, PubMed:20144788). Found in a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (By similarity). Within the PRC2 complex, interacts directly with SUZ12; competes with PHF19 for SUZ12 binding (By similarity). Interacts with EED, EZH2, and RBBP4 (By similarity). May also interact with RBBP7 (By similarity). http://togogenome.org/gene/10090:Plpp2 ^@ http://purl.uniprot.org/uniprot/A0A1W2P7I9|||http://purl.uniprot.org/uniprot/G3XA61|||http://purl.uniprot.org/uniprot/Q9DAX2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Cell membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Expressed at high levels in lung, liver and kidney; at low levels in heart and brain, and was not detected in skeletal muscle.|||Forms functional homodimers and homooligomers. Can also form heterooligomers with PLPP1 and PLPP3.|||Magnesium-independent phospholipid phosphatase that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P. Has no apparent extracellular phosphatase activity and therefore most probably acts intracellularly. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound. Through dephosphorylation of these bioactive lipid mediators produces new bioactive compounds and may regulate signal transduction in different cellular processes (By similarity). Indirectly regulates, for instance, cell cycle G1/S phase transition through its phospholipid phosphatase activity (By similarity).|||Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide.|||Membrane|||Mice lacking Plpp2 do not show overt phenotype (PubMed:10992322). Born at the expected Mendelian frequency they are perfectly viable and fertile (PubMed:10992322).|||N-glycosylated. http://togogenome.org/gene/10090:Camkv ^@ http://purl.uniprot.org/uniprot/Q3UHL1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Does not appear to have detectable kinase activity.|||Interacts with calmodulin, in the presence of calcium.|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Or12j5 ^@ http://purl.uniprot.org/uniprot/Q8VFE9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nsun2 ^@ http://purl.uniprot.org/uniprot/Q1HFZ0 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.|||By Myc (at protein level).|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Detected from 3.5 dpc in the inner cell mass of the blastocyst (PubMed:22144916). Expressed throughout the extra-embryonic ectoderm, which gives rise to the nervous system and epidermis, after implantation and gastrulation (PubMed:22144916). Starting from 9.5 dpc, expression becomes more restricted and at 13.5 and 14.5 dpc it is enriched in developing whiskers and eyes (PubMed:22144916). From 15.5 dpc, when the interfollicular epidermis begins to stratify and follicular morphogenesis starts by forming hair placodes, highest expression is observed in the suprabasal layer of interfollicular epidermis (PubMed:22144916).|||Inhibited by magnesium ions.|||Interacts with NPM1 and NCL during interphase; interaction is disrupted following phosphorylation at Ser-139.|||Mice are viable but show male sterility (PubMed:22144916, PubMed:23401851). Mice display reduced body weight and partial alopecia; alopecia is caused by impaired stem cell differentiation in the epidermis, leading to a delay in initiation of anagen (PubMed:22144916). Mice lacking both Nsun2 and Trdmt1 display a complete loss of cytosine-C5 tRNA methylation, leading to development defects and impaired cellular differentiation causing lethality before P3 (PubMed:22885326). Male sterility is caused by impaired germ cell differentiation in the testis: meiotic progression of germ cells is blocked into the pachytene stage, while spermatogonial and Sertoli cells are unaffected (PubMed:23401851).|||Mitochondrion|||Phosphorylated at Ser-139 by AURKB during mitosis, leading to abolish methyltransferase activity and the interaction with NPM1.|||RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs) (PubMed:22144916, PubMed:23871666, PubMed:31199786). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay (PubMed:22144916, PubMed:22885326, PubMed:23401851, PubMed:31199786). Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors (PubMed:22885326, PubMed:23871666, PubMed:31199786). tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs) (PubMed:31199786). Also mediates C(5)-methylation of mitochondrial tRNAs (PubMed:31276587, PubMed:31287866). Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay: mRNA stabilization involves YBX1 that specifically recognizes and binds m5C-modified transcripts (By similarity). Cytosine C(5)-methylation of mRNAs also regulates mRNA export: methylated transcripts are specifically recognized by THOC4/ALYREF, which mediates mRNA nucleo-cytoplasmic shuttling (By similarity). Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs (PubMed:23871666). Cytosine C(5)-methylation of vtRNA VTRNA1.1 promotes its processing into small-vault RNA4 (svRNA4) and regulates epidermal differentiation (By similarity). May act downstream of Myc to regulate epidermal cell growth and proliferation (PubMed:16713953). Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity (PubMed:19596847).|||Ubiquitously expressed at low level (PubMed:16713953). Up-regulated in tumors (PubMed:16713953). Dynamically expressed during morphogenesis and in adult skin: in adult skin, expression is up-regulated in the bulge and hair germ as soon as the hair follicle enters its growing phase (anagen) (PubMed:22144916). During anagen, expressed at highest level in cells of the hair germ that give rise to the hair matrix (PubMed:22144916).|||extracellular exosome|||nucleolus|||spindle http://togogenome.org/gene/10090:Ston2 ^@ http://purl.uniprot.org/uniprot/Q8BZ60 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein involved in endocytic machinery. Involved in the synaptic vesicle recycling. May facilitate clathrin-coated vesicle uncoating (By similarity).|||Belongs to the Stoned B family.|||Cytoplasm|||Interacts with the second C2 domain of synaptotagmins SYT1 and SYT2. Interacts with EPS15, EPS15R and ITSN1. Interacts indirectly with the AP-2 adapter complex. Interacts with TOR1A and COPS4; the interaction controls STON2 protein stability (By similarity).|||Membrane|||Neddylated; deneddylated via its interaction with the COP9 signalosome (CSN) complex through TOR1A and COPS4.|||Phosphorylated in vitro by PKD.|||The Asn-Pro-Phe (NPF) motifs, which are found in proteins involved in the endocytic pathway, mediate the interaction with the EH domain of SYT1, SYT2, EPS15, EPS15R and ITSN1.|||Ubiquitinated; leading to its degradation.|||synaptosome http://togogenome.org/gene/10090:Bpi ^@ http://purl.uniprot.org/uniprot/Q67E05 ^@ Biotechnology|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||By lipopolysaccharide (LPS) through TRL4-TRIF-dependent pathway. Expression in Sertoli and promyelocytic cells is enhanced several-fold by all-trans retinoic acid.|||Cytoplasmic granule membrane|||Expressed in testis, epididymis, and bone marrow, as well as in Sertoli and promyelocytic cell lines. Upon stimulation with different TLR ligands, it is strongly expressed in granulocytes and in bone marrow-derived dendritic cells.|||Monomer. Homodimer; disulfide-linked.|||Secreted|||The 199 N-terminal fragment fused to gas vesicle protein C (gvpC1) of H.salinarum, when incorporated in gas vesicles (GV), increases the survival rate of mice challenged with lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine, if GVs are administered before challenge.|||The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues.|||The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested.|||The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. http://togogenome.org/gene/10090:Cldn34c3 ^@ http://purl.uniprot.org/uniprot/A0A991ENX4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Tnfrsf10b ^@ http://purl.uniprot.org/uniprot/Q9QZM4 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Glycosylated at Arg-293 by S.typhimurium protein Ssek3.|||Highly expressed in heart, lung and kidney.|||Membrane|||Monomer. Can interact with TRADD and RIPK1. Three TNFRSF10B molecules interact with the TNFSF10 homotrimer. In the absence of stimulation, interacts with BIRC2, DDX3X and GSK3B. The interaction with BIRC2 and DDX3X is further enhanced upon receptor stimulation and accompanied by DDX3X and BIRC2 cleavage (By similarity).|||Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.|||TNFRSF10B is regulated by the tumor suppressor p53. http://togogenome.org/gene/10090:Tcea3 ^@ http://purl.uniprot.org/uniprot/P23881 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TFS-II family.|||Chimeric cDNA. The sequence from position 1 to 95 is due to a chimeric cDNA.|||Liver, kidney and heart.|||Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.|||Nucleus http://togogenome.org/gene/10090:Bmper ^@ http://purl.uniprot.org/uniprot/Q8CJ69 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ At 9.0 dpc, expressed in the ventral tail bud and also in the closing anterior neuropore and in the roof of the neural tube, at 10.5 dpc, also expressed in mesonephric ridge.|||Inhibitor of bone morphogenetic protein (BMP) function, it may regulate BMP responsiveness of osteoblasts and chondrocytes.|||Interacts with BMP4.|||Secreted http://togogenome.org/gene/10090:Zmym2 ^@ http://purl.uniprot.org/uniprot/Q9CU65 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can form homodimers (By similarity). May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with FOXP1 and FOXP2 (By similarity).|||Involved in the negative regulation of transcription.|||Low but widespread expression is detected in the developing kidney.|||Nucleus http://togogenome.org/gene/10090:Or51f1 ^@ http://purl.uniprot.org/uniprot/Q7TRS5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or51k1 ^@ http://purl.uniprot.org/uniprot/Q8VGY8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Schip1 ^@ http://purl.uniprot.org/uniprot/P0DPB4 ^@ Disruption Phenotype|||Sequence Caution|||Similarity|||Subunit ^@ Aberrant splicing.|||Belongs to the SCHIP1 family.|||Homooligomer (via coiled coil domain) (By similarity). Interacts with NF2; the interaction is direct (By similarity). Interacts with ANK3 (By similarity).|||Mice lacking all isoforms encoded by both Schip1 and Iqcj-Schip1 are fertile and survive as long as wild-type mice. However, they exhibit mild growth delay associated with ataxia and reduced pain sensitivity. They display decreased thickness of the piriform cortex and partial agenesis of the anterior comissure which could be due to impaired axon elongation and guidance. The morphology of nodes of Ranvier is affected but nerves do not exhibit significant electrophysiological characteristic differences. A reduction in the number of axonal projections in the peripheral nerve system is also observed.|||Probable cloning artifact. http://togogenome.org/gene/10090:Dsp ^@ http://purl.uniprot.org/uniprot/E9PZW0|||http://purl.uniprot.org/uniprot/E9Q557 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the plakin or cytolinker family.|||Cell membrane|||Homodimer (By similarity). Interacts with COL17A1 (via cytoplasmic region) (By similarity). Interacts with DSC2 (By similarity). Interacts with PKP1 (By similarity). Interacts with PKP2 (By similarity). Interacts weakly with TMEM65 (PubMed:26403541).|||Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity).|||The N-terminal region is required for localization to the desmosomal plaque and interacts with the N-terminal region of PKP1.|||desmosome http://togogenome.org/gene/10090:1700071K01Rik ^@ http://purl.uniprot.org/uniprot/Q3V2K0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the prohibitin family.|||Cell membrane|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cep70 ^@ http://purl.uniprot.org/uniprot/Q6IQY5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Directly interacts with tubulin-gamma; this interaction determines centrosomal localization.|||Plays a role in the organization of both preexisting and nascent microtubules in interphase cells. During mitosis, required for the organization and orientation of the mitotic spindle (By similarity).|||The coiled-coil domains may be important for tubulin-gamma-binding and hence for centrosomal localization.|||centrosome http://togogenome.org/gene/10090:Rnf41 ^@ http://purl.uniprot.org/uniprot/Q8BH75 ^@ Function|||Miscellaneous|||PTM|||Subunit ^@ Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88 (By similarity). Negatively regulates MYD88-dependent production of pro-inflammatory cytokines. Can promote TRIF-dependent production of type I interferon and inhibits infection with vesicular stomatitis virus. Promotes also activation of TBK1 and IRF3 (PubMed:19483718). Involved in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages (PubMed:18495327). Contributes to the maintenance of steady-state ERBB3 levels by mediating its growth factor-independent degradation. Involved in the degradation of the inhibitor of apoptosis BIRC6 and thus is an important regulator of cell death by promoting apoptosis. Acts also as a PRKN modifier that accelerates its degradation, resulting in a reduction of PRKN activity, influencing the balance of intracellular redox state. The RNF41-PRKN pathway regulates autophagosome-lysosome fusion during late mitophagy. Mitophagy is a selective form of autophagy necessary for mitochondrial quality control (PubMed:24949970).|||Autoubiquitinated. Autoubiquitination leads to proteasomal degradation. Deubiquitinated by USP8 to get stabilized which induces apoptosis.|||Interacts with USP8, ERBB3, PRKN and BIRC6 (By similarity). Interacts with CSF2RB, EPOR, IL3RA, MYD88 and TBK1. Interacts with Clec16a (PubMed:24949970).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Man2b2 ^@ http://purl.uniprot.org/uniprot/O54782 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 38 family.|||Binds 1 zinc ion per subunit.|||Mainly expressed in the narrow region between the caput and corpus epididymis.|||Plays an important role in the early step of spermatogenesis.|||Secreted|||Specifically expressed in type A spermatogonia at stages IX-XI of spermatogenesis. Detected there until the cell developed into type B spermatogonia. http://togogenome.org/gene/10090:Septin14 ^@ http://purl.uniprot.org/uniprot/Q9DA97|||http://purl.uniprot.org/uniprot/S4R2P6 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Expressed in the cerebral cortex from 15.5 dpc reaching maximum expression at 17.5 dpc, expression remains robust until P30 (PubMed:20181826). Expressed in early elongating spermatids during spermiogenesis (PubMed:33228246).|||Expressed in the testis and brain including the cerebrum, hippocampus and cerebellum (at protein level).|||Filament-forming cytoskeletal GTPase (Probable). Involved in the migration of cortical neurons and the formation of neuron leading processes during embryonic development (PubMed:20181826). Plays a role in sperm head formation during spermiogenesis, potentially via facilitating localization of ACTN4 to cell filaments (By similarity).|||Filament-forming cytoskeletal GTPase.|||Intron retention.|||Perikaryon|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Interacts with ACTN4 (PubMed:33228246). Interacts with SEPTIN9 (By similarity). Interacts (via C-terminus) with SEPTIN4 (PubMed:20181826).|||Septins polymerize into heterooligomeric protein complexes that form filaments.|||acrosome|||axon|||cytoskeleton|||dendrite|||perinuclear region http://togogenome.org/gene/10090:Cplx4 ^@ http://purl.uniprot.org/uniprot/Q80WM3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the complexin/synaphin family.|||Cell membrane|||Complexin that regulates SNARE protein complex-mediated synaptic vesicle fusion (PubMed:19386896). Required for the maintenance of synaptic ultrastructure in the adult retina (PubMed:19386896). Positively regulates synaptic transmission through synaptic vesicle availability and exocytosis of neurotransmitters at photoreceptor ribbon synapses in the retina (PubMed:15911881, PubMed:19386896, PubMed:27335398). Suppresses tonic photoreceptor activity and baseline 'noise' by suppression of Ca(2+) vesicle tonic release and the facilitation of evoked synchronous and asynchronous Ca(2+) vesicle release (PubMed:22694764, PubMed:27335398).|||Farnesylation mediates presynaptic targeting and is important for function in neurotransmitter release.|||Knockout mice are generally phenotypically normal, viable, and fertile (PubMed:19386896). Normal overall retina structure and morphology of the outer plexiform layer (OPL) and inner plexiform layer (IPL) (PubMed:19386896). Abundance and distribution of synaptic proteins remain consistent (PubMed:19386896). Reduced inner retinal processing and retinal synaptic transmission at low light intensities (PubMed:19386896). Cplx3 and Cplx4 double knockout mice are generally phenotypically normal, viable, and fertile, however show disordered morphology of the OPL and vision perturbation when compared to single knockout mice (PubMed:19386896). Cplx3 and Cplx4 double knockout mice show evidence of mild vision perturbation, with a reduction in the number of morphologically normal anchored presynaptic ribbon synapses and a decrease in controlled neurotransmitter release at photoreceptor ribbon synapses (PubMed:19386896). Cplx3 and Cplx4 double knockout mice show a reduced response and sensitivity of ON and OFF ganglion cell response as a result of disrupted synaptic transmission (PubMed:22694764). Cplx3 and Cplx4 double knockout mice show a greater variance in photoreceptor activity response and a decrease in sustained response, this is caused by an increase in release and fusion of synaptic vesicles in an asynchronous manner, this is particularly evident following multiple stimuli (PubMed:27335398).|||Present specifically in the retina (at protein level) (PubMed:15911881, PubMed:19386896, PubMed:22694764, PubMed:27335398). Expressed in the outer nuclear layer of the retina (at protein level) (PubMed:22694764). Strongly expressed at rod photoreceptor ribbon synapses (at protein level) (PubMed:15911881, PubMed:22694764). Not expressed at conventional amacrine cell synapses, nor at cone photoreceptor ribbon synapses (at protein level) (PubMed:15911881). Weakly expressed at cone photoreceptor synaptic terminals (at protein level) (PubMed:22694764). Not expressed in the brain (at protein level) (PubMed:19386896).|||Synapse|||Weakly binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A. http://togogenome.org/gene/10090:Htra2 ^@ http://purl.uniprot.org/uniprot/Q9JIY5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoproteolytically activated.|||Belongs to the peptidase S1C family.|||Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions (By similarity). The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4 (By similarity). Interacts with BIRC6/bruce (By similarity). Interacts with AREL1 (via HECT domain); in the cytoplasm following induction of apoptosis (PubMed:23479728).|||Mitochondrion intermembrane space|||Mitochondrion membrane|||Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase-independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis (By similarity).|||The PDZ domain mediates interaction with MXI2.|||The mature N-terminus is involved in the interaction with XIAP. http://togogenome.org/gene/10090:Il4i1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0C2|||http://purl.uniprot.org/uniprot/O09046 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the flavin monoamine oxidase family.|||Belongs to the flavin monoamine oxidase family. FIG1 subfamily.|||By interleukin-4.|||Expression increases during bone marrow-derived macrophage (BMDM) differentiation: expression is much higher in primary macrophages than monocytes.|||Lysosome|||Mice display an accelerated B-cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B-cells.|||Primarily found in immune tissues, mostly in B-lymphocytes.|||Primarily found in immune tissues.|||Restricted to the testis, predominantly in Sertoli cells at the periphery of the ducts, and the brain, including Purkinje cells, hippocampus and mitral cells in the olfactory bulb. No isoform 2 expression in fetal tissues.|||Secreted|||Secreted L-amino-acid oxidase that acts as a key immunoregulator (PubMed:32818467). Has preference for L-aromatic amino acids: converts phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) to phenylpyruvic acid (PP), hydroxyphenylpyruvic acid (HPP), and indole-3-pyruvic acid (I3P), respectively (PubMed:15383589). Also has weak L-arginine oxidase activity (By similarity). Acts as a negative regulator of anti-tumor immunity by mediating Trp degradation via an indole pyruvate pathway that activates the transcription factor AHR (PubMed:21469114, PubMed:28405502, PubMed:32818467). IL4I1-mediated Trp catabolism generates I3P, giving rise to indole metabolites (indole-3-acetic acid (IAA) and indole-3-aldehyde (I3A)) and kynurenic acid, which act as ligands for AHR, a ligand-activated transcription factor that plays important roles in immunity and cancer (By similarity). AHR activation by indoles following IL4I1-mediated Trp degradation enhances tumor progression by promoting cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Also has an immunoregulatory function in some immune cell, probably by mediating Trp degradation and promoting downstream AHR activation: inhibits T-cell activation and proliferation, promotes the differentiation of naive CD4(+) T-cells into FOXP3(+) regulatory T-cells (Treg) and regulates the development and function of B-cells (PubMed:25778793, PubMed:29288206). Also regulates M2 macrophage polarization by inhibiting T-cell activation (PubMed:26599209). Also has antibacterial properties by inhibiting growth of Gram negative and Gram positive bacteria through the production of NH4(+) and H2O2 (By similarity).|||Uses the promoter of the upstream NUP62 gene and shares the first 2 non-coding exons with NUP62.|||acrosome http://togogenome.org/gene/10090:Ddx6 ^@ http://purl.uniprot.org/uniprot/P54823 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Abundant expression in growing oocytes, levels decline in primary and secondary oocytes, and degradation appears to be complete by the mid-late two-cell stage.|||Belongs to the DEAD box helicase family. DDX6/DHH1 subfamily.|||Cytoplasm|||Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions (By similarity). Plays a role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (By similarity). In the process of mRNA degradation, plays a role in mRNA decapping (By similarity). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573).|||Interacts with LSM14A, LSM14B, EIF4ENIF1/4E-T, PATL1, EDC3 and EDC4 (By similarity). Forms a complex with DCP1A, DCP2, EDC3 and EDC4/HEDLS (By similarity). Interacts with LIMD1, WTIP and AJUBA (By similarity). Interacts with APOBEC3G in an RNA-dependent manner (By similarity). Interacts with RC3H1 (PubMed:20639877). Interacts with ATXN2L (By similarity). Interacts with MCRIP1 (By similarity). Interacts with MCRIP2 (By similarity). Interacts with NUFIP2 (By similarity). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (By similarity). Interacts with GIGYF1 and GIGYF2 (By similarity).|||Nucleus|||P-body|||Sumoylated. http://togogenome.org/gene/10090:Ugt1a6a ^@ http://purl.uniprot.org/uniprot/Q64435 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UDP-glycosyltransferase family.|||By dioxin.|||Endoplasmic reticulum membrane|||Expressed in liver, kidney and at very low levels in colon.|||Microsome|||UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Conjugates small planar phenolic molecules such as 4-nitrophenol, 1-naphthol, and 4-methylumbelliferone. The bulky phenol 4-hydroxybiphenyl, androgens and estrogens are not substrates. 2-hydroxybiphenyl is an excellent substrate. http://togogenome.org/gene/10090:Ccdc34 ^@ http://purl.uniprot.org/uniprot/Q3UI66|||http://purl.uniprot.org/uniprot/Q8BIA8 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in testis and sperm.|||Involved in spermatogenesis. Has a probable role in anterograde intraflagellar transport which is essential for the formation of sperm flagella.|||flagellum http://togogenome.org/gene/10090:Rnf38 ^@ http://purl.uniprot.org/uniprot/Q8BI21 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Acts as an E3 ubiquitin-protein ligase able to ubiquitinate p53/TP53 which promotes its relocalization to discrete foci associated with PML nuclear bodies. Exhibits preference for UBE2D2 as a E2 enzyme.|||Chimeric cDNA. Chimeric cDNA originating from chromosomes 1 and 4.|||Nucleus http://togogenome.org/gene/10090:Sh3kbp1 ^@ http://purl.uniprot.org/uniprot/Q8R550 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration (By similarity). Has an essential role in the stimulation of B cell activation (By similarity).|||Can self-associate and form homotetramers. Interacts with CD2, F-actin capping protein, PIK3R3, GRB2, EGFR, MET, BLNK, MAP3K4, PDCD6IP, SPRY2, ARHGAP17, ARHGAP27, CRK, BCAR1, SOS1, ASAP1, ARAP3, HIP1R, SYNJ2, INPP5D and STAP1 (By similarity). Interacts with CBL (PubMed:21830225). Interacts with CBLB, but does not interact with CBLC. Two molecules of SH3KBP1 seem to bind through their respective SH3 1 domain to one molecule of CBLB. The interaction with CBL or CBLB and EGFR is increased upon EGF stimulation. The interaction with CBL is attenuated by PDCD6IP. Interacts through its proline-rich region with the SH3 domain of endophilins SH3GL1, SH3GL2 and SH3GL3. The SH3KBP1-endophilin complex seems to associate with a complex containing the phosphorylated receptor (EGFR or MET) and phosphorylated CBL. Probably associates with ASAP1 and phosphorylated EGFR. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3. Interacts with focal adhesion kinases PTK2/FAK1 and PTK2B/PYK2, probably as a dimer. Interacts with DAB2 and probably associates with chathrin through its interaction with DAB2. Part of a complex consisting of SH3KBP1, DAB2, and clathrin heavy chain. DAB2 and clathrin dissociate from SH3KBP1 following growth factor treatment, enabling interaction with CBL. Interacts with DDN and probably associates with MAGI2 through its interaction with DDN. Interacts with the SH3 domains of SRC tyrosine-protein kinases SRC, LCK, LYN, FGR, FYN and HCK. Interacts with TRADD, BIRC2, TRAF1, TRAF2 and TNFR1, and the association with a TNFR1-associated complex upon stimulation with TNF-alpha seems to be mediated by SRC. Probably part of a complex consisting of at least SH3KBP1, ASAP1 and ARAP3 (By similarity). Interacts (via SH3 domains) with SHKBP1 (via PXXXPR motifs) (PubMed:11152963, PubMed:21830225). Interacts with ATX2 (PubMed:18602463). Interaction with CBL is abolished in the presence of SHKBP1 (PubMed:21830225). Interacts (via SH3 domains) with ZFP36 (via extreme C-terminal region). Interacts with MAP3K4; this interaction enhances the association with ZFP36 (By similarity).|||Cytoplasm|||Cytoplasmic vesicle membrane|||Monoubiquitinated by CBL and CBLB after EGF stimulation; probably on its C-terminus.|||cytoskeleton|||focal adhesion|||synaptosome http://togogenome.org/gene/10090:Zfp689 ^@ http://purl.uniprot.org/uniprot/Q8BKK5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Tcea1 ^@ http://purl.uniprot.org/uniprot/E9PYD5|||http://purl.uniprot.org/uniprot/P10711|||http://purl.uniprot.org/uniprot/Q3UWX7 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with UBR5 and forms a transcription regulatory complex made of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulates target gene transcription by recruiting their promoters (By similarity). Interacts with EAF2.|||Belongs to the TFS-II family.|||Chimeric cDNA.|||Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.|||Nucleus|||S-II binds to RNA-polymerase II in the absence of transcription. http://togogenome.org/gene/10090:Dnajc8 ^@ http://purl.uniprot.org/uniprot/Q6NZB0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with SRPK1. Interacts with HSP70 (HSPA1A or HSPA1B).|||Nucleus|||Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells. http://togogenome.org/gene/10090:Kcns3 ^@ http://purl.uniprot.org/uniprot/Q8BQZ8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. S (TC 1.A.1.2) subfamily. Kv9.3/KCNS3 sub-subfamily.|||Cell membrane|||Heterotetramer with KCNB1. Does not form homomultimers.|||Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1. Heterotetrameric channel activity formed with KCNB1 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. http://togogenome.org/gene/10090:Ltbp2 ^@ http://purl.uniprot.org/uniprot/O08999|||http://purl.uniprot.org/uniprot/Q0VD84 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LTBP family.|||Contains hydroxylated asparagine residues.|||Expressed in the anterior chamber of the eye.|||Forms part of the large latent transforming growth factor beta precursor complex; removal is essential for activation of complex. Interacts with SDC4. Interacts (via C-terminal domain) with FBN1 (via N-terminal domain) in a Ca(+2)-dependent manner.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May play an integral structural role in elastic-fiber architectural organization and/or assembly.|||N-Glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Lum ^@ http://purl.uniprot.org/uniprot/P51885 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.|||Binds to laminin.|||Contains keratan sulfate.|||Cornea and other tissues.|||Cys-37, Cys-41, Cys-43 and Cys-53 are involved in disulfide bonds.|||extracellular matrix http://togogenome.org/gene/10090:Rad9b ^@ http://purl.uniprot.org/uniprot/Q6WBX7|||http://purl.uniprot.org/uniprot/Q8VC54 ^@ Similarity|||Subunit ^@ Belongs to the rad9 family.|||Interacts with HUS1, HUS1B, RAD1, RAD9A and RAD17. http://togogenome.org/gene/10090:Ralgapa1 ^@ http://purl.uniprot.org/uniprot/Q6GYP7 ^@ Caution|||Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB (By similarity). May interact with the HLH region of TCF3/isoform E12.|||Component of the heterodimeric RalGAP1 complex with RALGAPB. Heterodimerization is required for activity (By similarity). Interacts with the HLH region of TCF3/isoform E12.|||Cytoplasm|||Expressed during embryogenesis. Expressed in the adult brain, particularly in neurons of the cortex and hippocampus.|||Expression decreased during development, but persists in the adult brain.|||May be a partial isoform 1.|||Nucleus|||Was initially thought to act as a transcriptional regulator via its interaction with TCF3/E12. http://togogenome.org/gene/10090:Zfp426 ^@ http://purl.uniprot.org/uniprot/Q8R1D1 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Exon deletion.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Kif2c ^@ http://purl.uniprot.org/uniprot/Q3TTL2|||http://purl.uniprot.org/uniprot/Q3UD72|||http://purl.uniprot.org/uniprot/Q922S8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. MCAK/KIF2 subfamily.|||In complex with KIF18B, constitutes the major microtubule plus-end depolymerizing activity in mitotic cells (PubMed:14980225). Regulates the turnover of microtubules at the kinetochore and functions in chromosome segregation during mitosis. Plays a role in chromosome congression and is required for the lateral to end-on conversion of the chromosome-microtubule attachment (By similarity).|||Interacts with CENPH. Interacts with MTUS2/TIP150; the interaction is direct. Interacts with MAPRE1; the interaction is direct, regulated by phosphorylation and is probably required for targeting to growing microtubule plus ends. Interacts with KIF18B at microtubule tips; this interaction increases the affinity of both partners for microtubule plus ends and is required for robust microtubule depolymerization. Phosphorylation by AURKA or AURKB strongly reduces KIF18B-binding.|||Nucleus|||Phosphorylation by AURKB, regulates association with centromeres and kinetochores and the microtubule depolymerization activity.|||The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.|||Ubiquitinated.|||centromere|||cytoskeleton|||kinetochore http://togogenome.org/gene/10090:Cyp2e1 ^@ http://purl.uniprot.org/uniprot/Q05421 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids. May be involved in the oxidative metabolism of xenobiotics.|||Belongs to the cytochrome P450 family.|||By ethanol and acetone in the liver and by testosterone in the kidney and adrenal tissues.|||Detectable in the female liver on day 1 and reaches steady state levels on days 16-20.|||Endoplasmic reticulum membrane|||Highest level in the liver and to a lesser extent in the kidney, with a higher level in the male kidney than in the female.|||Interacts with chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria.|||Microsome membrane|||Mitochondrion inner membrane|||The omega-1 hydroxylase activity is stimulated by cytochrome b5. http://togogenome.org/gene/10090:Gm20917 ^@ http://purl.uniprot.org/uniprot/Q62457 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Vmn1r31 ^@ http://purl.uniprot.org/uniprot/H3BKW5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zscan18 ^@ http://purl.uniprot.org/uniprot/E9PUD6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ggt1 ^@ http://purl.uniprot.org/uniprot/Q4FK56|||http://purl.uniprot.org/uniprot/Q60928 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by autocatalytic cleavage.|||Belongs to the gamma-glutamyltransferase family.|||Cell membrane|||Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.|||Cleaves the gamma-glutamyl bond of extracellular glutathione (gamma-Glu-Cys-Gly), glutathione conjugates (such as maresin conjugate (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate, MCTR1) and other gamma-glutamyl compounds (such as leukotriene C4, LTC4). The metabolism of glutathione by GGT1 releases free glutamate and the dipeptide cysteinyl-glycine, which is hydrolyzed to cysteine and glycine by dipeptidases. In the presence of high concentrations of dipeptides and some amino acids, can also catalyze a transpeptidation reaction, transferring the gamma-glutamyl moiety to an acceptor amino acid to form a new gamma-glutamyl compound. Contributes to cysteine homeostasis, glutathione homeostasis and in the conversion of the leukotriene LTC4 to LTD4 (By similarity). Indirectly regulates multiple aspects of skeletal biology (PubMed:12810527).|||Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione conjugates.|||Defects in Ggt1 are a cause of glutathionuria, severe growth failure, reduced life spans and infertility. Ggt1-deficient mice have multiple metabolic abnormalities and are dwarf. Some abnormalities can be ameliorated by N-acetylcysteine treatment.|||Deficient mice have growth retardation, skeletal abnormalities. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. They cannot break down GSH into its constituent amino acids as it passes through the proximal tubules of the kidney. They excrete large amounts of GSH in their urine, leading to a fatal cysteine deficiency.|||Heterodimer composed of the light and heavy chains. The active site is located in the light chain.|||Membrane|||N-glycosylated on both chains. http://togogenome.org/gene/10090:Fut10 ^@ http://purl.uniprot.org/uniprot/Q5F2L2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 10 family.|||Endoplasmic reticulum membrane|||Expressed by Lewis X-positive neural precursor cells in the ventricular and subventricular zones of 15.5 dpc embryonic brain.|||Golgi apparatus membrane|||Predominantly fucosylates the innermost N-acetyl glucosamine (GlcNAc) residue in biantennary N-glycan acceptors. Postulated to generate core alpha(1->3)-fucose epitope within the chitobiose unit of biantennary N-glycans, providing for a recognition signal to reorient aberrantly folded glycoproteins for degradation (By similarity). Involved in biosynthesis of Lewis X-carrying biantennary N-glycans that regulate neuron stem cell self-renewal during brain development (PubMed:23986452).|||Widely expressed, with a higher expression in liver and thymus. http://togogenome.org/gene/10090:Fntb ^@ http://purl.uniprot.org/uniprot/Q8K2I1 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the protein prenyltransferase subunit beta family.|||Binds 1 zinc ion per subunit.|||Essential subunit of the farnesyltransferase complex. Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.|||Heterodimer of FNTA and FNTB. http://togogenome.org/gene/10090:Trim31 ^@ http://purl.uniprot.org/uniprot/Q8R0K2 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated (in vitro).|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin-protein ligase that acts as a regulator of antiviral immune response and inflammation by mediating ubiquitination of substrates (PubMed:27929086, PubMed:27992402). Acts as a regulator of innate immune defense against viruses by mediating 'Lys-63'-linked ubiquitination of MAVS, promoting MAVS polymerization and formation of three-stranded helical filaments on mitochondria (PubMed:27992402). Acts as a negative regulator of the NLRP3 inflammasome by catalyzing 'Lys-48'-linked ubiquitination of NLRP3, leading to its degradation (PubMed:27929086). Regulator of Src-induced anchorage independent cell growth (PubMed:19665990).|||Highly expressed in the gastrointestrinal tract, with high expression in the small intestine, moderate in the large intestine and weak in the stomach and esophagus.|||May form oligomers (By similarity). Interacts with isoform p52shc of SHC1 (PubMed:19665990).|||Mice are viable, normal in size and without gross physiological or behavioral abnormalities (PubMed:27992402). Mice are however more susceptible to infection with RNA virus due to impaired cellular antiviral response (PubMed:27992402). Mice also show increased inflammatory response, characterized by enhanced NLRP3 inflammasome activation (PubMed:27929086). Increased NLRP3 inflammasome activation leads to an aggravation of alum-induced peritonitis (PubMed:27929086). In contrast, it attenuates the severity of dextran sodium sulfate-induced colitis, an inflammatory bowel diseases model in which NLRP3 possesses protective roles (PubMed:27929086).|||Mitochondrion|||Up-regulated in response to lipopolysaccharid and IL1B treatment. http://togogenome.org/gene/10090:Chrna3 ^@ http://purl.uniprot.org/uniprot/Q0VBK4|||http://purl.uniprot.org/uniprot/Q8R4G9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-3/CHRNA3 sub-subfamily.|||Cell membrane|||Membrane|||Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-3 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6. The heteropentamer alpha-3-beta-2 interacts with alpha-conotoxins ImI, ImII, PnIA, GID and MII. The heteropentamer alpha-3-beta-4 interacts with the alpha-conotoxin ImI.|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Tenm4 ^@ http://purl.uniprot.org/uniprot/Q3UHK6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tenascin family. Teneurin subfamily.|||Cell membrane|||Cell projection|||Cytoplasm|||Cytoplasmic proline-rich regions could serve as docking domains for intracellular SH3-containing proteins.|||EGF-like domains 2 and 5 which have an odd number of cysteines might enable the formation of intermolecular disulfide bonds.|||Expressed in brain and spinal cord (at protein level). Expressed in neurons and oligodendrocytes of the spinal cord. Expressed weakly in kidney, lung and spleen. Expressed in the cortex, CA1, CA2 and CA3 of the hippocampus. Expressed in the white matter, Purkinje cells and molecular layer of the cerebellum.|||Expressed in spinal cord at 18 dpc (at protein level). Expressed in the epiblast and extraembryonic regions as early as 6.5 dpc. Expressed in the neural plate and extraembryonic tissues at 7.5 dpc. Expressed in the forebrain, mid/hindbrain junction, somites and tail bud at 8.5 dpc. Expressed in the tail bud and limbs at 11.5 dpc. Expressed in the diencephalon and midbrain at 12.5 dpc.|||Homodimer; disulfide-linked. May also form heterodimer with either TENM1 or TENM2 or TENM3.|||Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Plays a role in the establishment of the anterior-posterior axis during gastrulation. Regulates the differentiation and cellular process formation of oligodendrocytes and myelination of small-diameter axons in the central nervous system (CNS). Promotes activation of focal adhesion kinase. May function as a cellular signal transducer.|||Mice show tremors and hypomyelination in the central nervous system (CNS), particularly in the spinal cord, but not in the sciatic nerve of the peripheral nervous system (PNS). Differentiation of oligodendrocytes is prevented in the spinal cord.|||Nucleus|||Up-regulated during oligodendrocyte differentiation. http://togogenome.org/gene/10090:Vmn1r124 ^@ http://purl.uniprot.org/uniprot/D3YTX4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nxpe2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0E5|||http://purl.uniprot.org/uniprot/Q3U095 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NXPE family.|||Membrane http://togogenome.org/gene/10090:Efcab6 ^@ http://purl.uniprot.org/uniprot/Q6P1E8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds PARK7. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR (By similarity).|||Negatively regulates the androgen receptor by recruiting histone deacetylase complex, and protein DJ-1 antagonizes this inhibition by abrogation of this complex. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||Nucleus|||cilium axoneme http://togogenome.org/gene/10090:Adam21 ^@ http://purl.uniprot.org/uniprot/Q9JI76 ^@ Cofactor|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ A tripeptide motif (VGE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.|||Binds 1 zinc ion per subunit.|||Has no obvious cleavage site for furin endopeptidase, suggesting that the proteolytic processing is regulated.|||Highly expressed in Leydig cells. Expressed also in cauda epididymidis, vas deferens, convoluted tubules, kidney and the parietal cells of stomach. Not detected on developing spermatocytes or mature sperm.|||May be involved in sperm maturation and/or fertilization. May also be involved in epithelia functions associated with establishing and maintaining gradients of ions or nutrients.|||Membrane|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The cysteine-rich domain encodes putative cell-fusion peptides, which could be involved in sperm-egg fusion. http://togogenome.org/gene/10090:Eef1a1 ^@ http://purl.uniprot.org/uniprot/P10126|||http://purl.uniprot.org/uniprot/Q58E64 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.|||Cell membrane|||Cytoplasm|||Found in a nuclear export complex with XPO5, EEF1A1, Ran and aminoacylated tRNA. Interacts with PARP1. Interacts with KARS1. May interact with ERGIC2. Interacts with IFIT1 (via TPR repeats 4-7) (By similarity). May interact with ERGIC2 (By similarity). Interacts with IFIT1 (via TPR repeats 4-7) (PubMed:19856081). Interacts with DLC1, facilitating distribution to the membrane periphery and ruffles upon growth factor stimulation. Interacts with ZPR1; the interaction occurs in a epidermal growth factor (EGF)-dependent manner (By similarity). Interacts with PPP1R16B (By similarity). Interacts with SPHK1 and SPHK2; both interactions increase SPHK1 and SPHK2 kinase activity (By similarity).|||ISGylated.|||Inhibited by plitidepsin, a chemical compound extracted from the ascidian Aplidium albicans.|||Nucleus|||Phosphorylated by TXK. Phosphorylation by PASK increases translation efficiency. Phosphorylated by ROCK2. Phosphorylation by TGFBR1 inhibits translation elongation.|||This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.|||Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome. The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation. Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1.|||Trimethylated at Lys-79 by EEF1AKMT1. Methylated at Lys-165 by EEF1AKMT3, methylation by EEF1AKMT3 is dynamic as well as inducible by stress conditions, such as ER-stress, and plays a regulatory role on mRNA translation. Trimethylated at Lys-318 by EEF1AKMT2. Mono-, di-, and trimethylated at Lys-36 by EEF1AKMT4; trimethylated form is predominant. Methylation by EEF1AKMT4 contributes to the fine-tuning of translation rates for a subset of tRNAs. Trimethylated at Gly-2 by METTL13. Mono- and dimethylated at Lys-55 by METTL13; dimethylated form is predominant.|||Ubiquitinated at Lys-385 by RNF14 in response to ribosome collisions (ribosome stalling), leading to its degradation by the proteasome and rescue of stalled ribosomes.|||nucleolus http://togogenome.org/gene/10090:Adamts19 ^@ http://purl.uniprot.org/uniprot/P59509 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||By homology with the human sequence, it is uncertain whether Met-1 or Met-5 is the initiator.|||Expressed predominantly in fetal ovary, low levels of expression is also detected in kidney, heart, skeletal muscle, lung and testis.|||Expression is strongest in anterior and ventral regions of the ovary at 12.5 and 13.5 dpc before becoming more uniform.|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Homozygous knockout mice are viable, fertile and born in Mendelian ratios. Echocardiographic analysis reveals progressive aortic valve disease, without dysfunction in any of other valves. Valve defects range from aortic regurgitation to severe aortic valve stenosis, or a combination of both. Dysfunctional aortic valves show thickening of the commissures with reduced opening of the valve, occasionally in a 'fish mouth' pattern with only 2 visible commissures, reminiscent of fused bicuspid aortic valves in humans. The extracellular matrix is disorganized throughout the aortic valve leaflets, with significant thickening at the hinge region of the leaflets and increased collagen deposition covering the raphe. There is no evidence of valve calcification.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||extracellular matrix http://togogenome.org/gene/10090:Atp8b4 ^@ http://purl.uniprot.org/uniprot/A1L3S5|||http://purl.uniprot.org/uniprot/A2ANX3|||http://purl.uniprot.org/uniprot/Q69Z59 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Or10ak14 ^@ http://purl.uniprot.org/uniprot/A0A1L1SSB4|||http://purl.uniprot.org/uniprot/A2ACY7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pdgfc ^@ http://purl.uniprot.org/uniprot/Q8CI19 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDGF/VEGF growth factor family.|||Cell membrane|||Cytoplasmic granule|||Expression decreased by hypoxia. Up-regulated by EWS-FLI1 transcription factor in tumor-derived cells. Up-regulated by IL13 overexpression in the lung via STAT6 and EGR1. Elevated expression induced by coxsackievirus B3 infection in immunodeficient mice. Overexpressed in the renal fibrosis. Expression in the lung is significantly increased after bleomycin treatment. Down-regulated by retinoic acid and gonadotropin.|||Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen and chemoattractant for cells of mesenchymal origin. Required for normal skeleton formation during embryonic development, especially for normal development of the craniofacial skeleton and for normal development of the palate. Required for normal skin morphogenesis during embryonic development. Plays an important role in wound healing, where it appears to be involved in three stages: inflammation, proliferation and remodeling. Plays an important role in angiogenesis and blood vessel development. Involved in fibrotic processes, in which transformation of interstitial fibroblasts into myofibroblasts plus collagen deposition occurs. The CUB domain has mitogenic activity in coronary artery smooth muscle cells, suggesting a role beyond the maintenance of the latency of the PDGF domain. In the nucleus, PDGFC seems to have additional function.|||Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB domain) with PLAT (via kringle domain) (By similarity).|||In stage 9.5 dpc-15.5 dpc, widely expressed in the surface ectoderm and later in the germinal layer of the skin, the olfactory and otic placode and their derivatives and the lining of the oral cavity. In stages 14.5 dpc-17.5 expressed in ducts connected to epidermis, and in developing epidermal openings. Highly expressed in the early stages of the developing kidney, in the metanephric mesenchymal aggregates, prefusion skeletal muscle, cardiac myoblasts, and in visceral and vascular smooth muscle.|||Involved in the development of myocarditis and subsequent fibrosis in the experimental model of coxsackievirus B3-induced chronic myocarditis.|||Mainly expressed in kidney, testis, liver, heart and brain (at protein level). Highly expressed in airway epithelium, interstitial cells and alveolar macrophages in the lung of mice overexpressing IL13. Expressed in the ovaries.|||N-glycosylated.|||Nucleus|||Perinatal lethality. Mice have feeding and respiratory difficulties due to a complete cleft of the secondary palate. However, they have reduction of renal fibrogenesis. Mice lacking both PDGFA and PDGFC develop a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects.|||Proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor-binding epitopes of the core domain. Cleavage after basic residues in the hinge region (region connecting the CUB and growth factor domains) gives rise to the receptor-binding form. Cleaved by PLAT and PLG (By similarity).|||Secreted|||Sumoylated by SUMO1.|||cytosol http://togogenome.org/gene/10090:Or5d16 ^@ http://purl.uniprot.org/uniprot/Q8VFR3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tubd1 ^@ http://purl.uniprot.org/uniprot/Q5SWF8|||http://purl.uniprot.org/uniprot/Q8CDD3|||http://purl.uniprot.org/uniprot/Q9R1K7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a positive regulator of hedgehog signaling and regulates ciliary function (PubMed:29290584).|||Belongs to the tubulin family.|||Cytoplasm|||Found in a complex with TEDC1, TEDC2, TUBE1 and TUBD1.|||Highly expressed in testis.|||Nucleus|||centriole|||cilium http://togogenome.org/gene/10090:Gopc ^@ http://purl.uniprot.org/uniprot/Q8BH60 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Golgi apparatus membrane|||Homooligomer (PubMed:11162552). Interacts with FZD5 (PubMed:11520064). Interacts with FZD8 (PubMed:11520064). Interacts with GRID2 and BECN1 (PubMed:12372286). Interacts with CSPG5 (PubMed:12885772). Interacts with CLCN3 (PubMed:12471024). Interacts with STX6 (By similarity). Interacts with CFTR (PubMed:12471024). Interacts with ASIC3 (PubMed:15317815). Interacts with GOLGA3 (By similarity). Interacts with NLGN1 (By similarity). Interacts with RHOQ (PubMed:11162552). Interacts with MARCHF2; the interaction leads to CFTR ubiquitination and degradation (By similarity). May interact with CACNG2 (PubMed:15136571). Interacts with CCDC62 (PubMed:28339613).|||In the cerebellum, expression increases post-natally, following maturation of this tissue (at protein level).|||Male mice are infertile with globozoospermia. Spermatozoa display a default in acrosome formation and are unable to activate oocytes.|||Plays a role in intracellular protein trafficking and degradation (PubMed:12149515). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (PubMed:15317815). May also regulate the intracellular trafficking of the ADR1B receptor (By similarity). May play a role in autophagy (PubMed:12372286). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (By similarity). Overexpression results in CFTR intracellular retention and degradation in the lysosomes (By similarity).|||Postsynaptic density|||Synapse|||The PDZ domain mediates interaction with ADRB1 (By similarity). Mediates also interactions with FZD5, FZD8, ASIC3, GRID2, CFTR, CLCN3.|||The coiled-coil region probably mediates targeting to the Golgi, oligomerization and interaction with RHOQ. May also mediates association to membranes and interactions with GOLGA3 and STX6 (By similarity).|||Ubiquitously expressed (at protein level). Expressed in dorsal root glanglion (DRG), spinal cord and brain. Isoform 1 is preferentially expressed in whole brain (at protein level) and cerebellum. Expressed in spermatocytes and spermatides but not in Sertoli cells and spermatogonia.|||dendrite|||trans-Golgi network membrane http://togogenome.org/gene/10090:Atg10 ^@ http://purl.uniprot.org/uniprot/Q8R1P4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATG10 family.|||Cytoplasm|||E2-like enzyme involved in autophagy. Acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5. ATG12 conjugation to ATG5 is required for autophagy. Likely serves as an ATG5-recognition molecule. Not involved in ATG12 conjugation to ATG3. Plays a role in adenovirus-mediated cell lysis.|||Interacts with MAP1LC3A. By interacting with MAP1LC3A, it plays a role in the conjugation of ATG12 to ATG5. Also able to directly interact either with ATG5 or ATG7. http://togogenome.org/gene/10090:Kdm6b ^@ http://purl.uniprot.org/uniprot/Q5NCY0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UTX family.|||By inflammatory stimuli; mediated by NF-kappa-B.|||Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code. Demethylates trimethylated and dimethylated H3 'Lys-27'. Plays a central role in regulation of posterior development, by regulating HOX gene expression. Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (PubMed:21095589).|||Interacts with TLE1 (PubMed:21095589). Component of the MLL4 complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, and KDM6B (By similarity). Interacts with TBX21, SMARCA4, SMARCC1 and SMARCC2 (PubMed:21095589).|||Nucleus http://togogenome.org/gene/10090:Or2y14 ^@ http://purl.uniprot.org/uniprot/Q8VFA8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or14c46 ^@ http://purl.uniprot.org/uniprot/B2RVZ1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcng4 ^@ http://purl.uniprot.org/uniprot/Q80XM3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. G (TC 1.A.1.2) subfamily. Kv6.4/KCNG4 sub-subfamily.|||Cell membrane|||Heterotetramer with KCNB1.|||Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. http://togogenome.org/gene/10090:Tbrg1 ^@ http://purl.uniprot.org/uniprot/Q3UB74 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a growth inhibitor. Can activate p53/TP53, causes G1 arrest and collaborates with CDKN2A to restrict proliferation, but does not require either protein to inhibit DNA synthesis. Redistributes CDKN2A into the nucleoplasm. Involved in maintaining chromosomal stability.|||Belongs to the TBRG1 family.|||Induced in cells undergoing arrest in response to DNA damage and TGFB1 treatment.|||Interacts with CDKN2A and MDM2.|||Nucleus|||Ubiquitinated; mediated by MDM2 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Tespa1 ^@ http://purl.uniprot.org/uniprot/Q3U132 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in lymphoid tissues, with highest expression levels detected in thymus and lower levels in spleen and lymph nodes (at protein level). Detected in CD4(+) and CD8(+) T-cells, B-cells and mast cells. Not detected in monocytes/macrophages.|||Interacts with PLCG1 and GRB2; the association is increased with prolonged stimulation of the TCR and may facilitate the assembly of the LAT signalosome (By similarity). Interacts with ITPR1 and ITPR3. Interacts with HSPA9 (By similarity).|||May be phosphorylated in response to store-operated Ca(+2) entry.|||May play a role in the regulation of inositol 1,4,5-trisphosphate receptor-mediated Ca(2+) release and mitochondrial Ca(2+) uptake via the mitochondria-associated endoplasmic reticulum membrane (MAM) compartment (By similarity). Required for the development and maturation of T-cells, its function being essential for the late stages of thymocyte development. Plays a role in T-cell antigen receptor (TCR)-mediated activation of the ERK and NFAT signaling pathways, possibly by serving as a scaffolding protein that promotes the assembly of the LAT signalosome in thymocytes.|||Mutant mice display defective T-cell development, resulting in notably fewer mature CD4(+) and CD8(+) cells in the thymus. The architecture of the thymus is altered, as characterized by smaller areas of the medulla. Mice also have fewer peripheral T-cells in spleen and display diminished T-cell antigen receptor (TCR)-mediated responses.|||Present in fetal thymus at 14.5 dpc. Expressed during thymocyte maturation, the expression being highest in CD4(+)CD8(+) thymocytes and decreasing with maturation. http://togogenome.org/gene/10090:Nlrp4g ^@ http://purl.uniprot.org/uniprot/Q3UWL9 ^@ Similarity ^@ Belongs to the NLRP family. http://togogenome.org/gene/10090:Ndrg4 ^@ http://purl.uniprot.org/uniprot/Q8BTG7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NDRG family.|||Contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress. May enhance growth factor-induced ERK1 and ERK2 phosphorylation. May attenuate NGF-promoted ELK1 phosphorylation in a microtubule-dependent manner.|||Mutant mice have impaired spatial learning and memory but normal motor function.|||Predominantly expressed in the brain (at protein level). Detected in neurons of various parts of brain, including the olfactory bulb, olfactory tuberculum, cerebral cortex, striatum, hippocampus, dentate gyrus, thalamus, hypothalamus, mesencephalon, cerebellum, pons and medulla oblongata.|||cytosol http://togogenome.org/gene/10090:Hikeshi ^@ http://purl.uniprot.org/uniprot/A0A140LJ25|||http://purl.uniprot.org/uniprot/Q9DD02 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a specific nuclear import carrier for HSP70 proteins following heat-shock stress: acts by mediating the nucleoporin-dependent translocation of ATP-bound HSP70 proteins into the nucleus. HSP70 proteins import is required to protect cells from heat shock damages. Does not translocate ADP-bound HSP70 proteins into the nucleus (By similarity). May also be indirectly required for organization and/or function of the secretory apparatus in Club cells in lung.|||Acts as a specific nuclear import carrier for HSP70 proteins following heat-shock stress: acts by mediating the nucleoporin-dependent translocation of ATP-bound HSP70 proteins into the nucleus. HSP70 proteins import is required to protect cells from heat shock damages. Does not translocate ADP-bound HSP70 proteins into the nucleus.|||Belongs to the OPI10 family.|||Cytoplasm|||During late gestation, it is expressed in lung epithelial cells, whereas perinatal expression is restricted to the bronchiolar epithelium.|||Expressed in the central white matter of newborn and adult brain, particularly in regions where oligodendrocytes are generated (PubMed:26545878).|||Forms an asymmetric homodimer; required for binding and nuclear import of HSP70 proteins. Interacts with ATP-bound HSP70 proteins.|||Forms an asymmetric homodimer; required for binding and nuclear import of HSP70 proteins. Interacts with ATP-bound HSP70 proteins. Interacts with NUP62 and NUP153 (via F-X-F-G repeats). Interacts with HSPA8.|||Mice display severe emphysematous enlargement of the distal respiratory sacs at birth. Club cells display enlargement and disorganization of the Golgi complex and formation of aberrant vesicular structures.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Slc35e2 ^@ http://purl.uniprot.org/uniprot/Q8C811 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPT transporter family. SLC35E subfamily.|||Membrane|||Putative transporter. http://togogenome.org/gene/10090:Drd1 ^@ http://purl.uniprot.org/uniprot/Q61616 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.|||Endoplasmic reticulum membrane|||Interacts with DNAJC14 via its C-terminus (By similarity). Interacts with DRD2 (PubMed:25865831).|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Vmn2r102 ^@ http://purl.uniprot.org/uniprot/L7N279 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tal1 ^@ http://purl.uniprot.org/uniprot/P22091 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Forms heterodimers with TCF3. Binds to the LIM domain containing protein LMO2 and to DRG1. Can assemble in a complex with LDB1 and LMO2. Component of a TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 (PubMed:9391090). Interacts with SBNO2; this interaction inhibits TAL1 occupancy of the DCSTAMP promoter, leading to the activation of the DCSTAMP promoter by the transcription factor MITF (PubMed:23980096).|||Erythroid and myeloid cells.|||Implicated in the genesis of hemopoietic malignancies. It may play an important role in hemopoietic differentiation. Serves as a positive regulator of erythroid differentiation.|||Nucleus|||Phosphorylated on serine residues. Phosphorylation of Ser-122 by MAPK is strongly stimulated by hypoxia.|||The helix-loop-helix domain is necessary and sufficient for the interaction with DRG1.|||Ubiquitinated; subsequent to hypoxia-dependent phosphorylation of Ser-122, ubiquitination targets the protein for rapid degradation via the ubiquitin system. This process may be characteristic for microvascular endothelial cells, since it could not be observed in large vessel endothelial cells. http://togogenome.org/gene/10090:Ifi211 ^@ http://purl.uniprot.org/uniprot/P0DOV1 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HIN-200 family.|||By lipopolysaccharides (LPS).|||Interacts with TP53, RB1, CDK1, CDK2 and HOXB2.|||May act as a transcriptional regulator in the myeloid lineage. Inhibits cell growth via p53/TP53 and RB1-dependent and independent pathways.|||Mononuclear phagocytes.|||Nucleus|||The family of genes to which Mnda belongs has undergone a rapid expansion in the mouse. As a consequence, mouse Mnda and human MNDA genes, although belonging to the same family, are not one to one orthologs. http://togogenome.org/gene/10090:Fcer2a ^@ http://purl.uniprot.org/uniprot/P20693 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Homotrimer. Interacts (via C-type lectin domain) with IGHE (via CH3 region); this interaction regulates IgE homeostasis. Interacts (via C-terminus) with CR2/CD21 (via Sushi domain 1 and 2).|||Low-affinity receptor for immunoglobulin E (IgE) and CR2/CD21. Has essential roles in the regulation of IgE production and in the differentiation of B cells. On B cells, initiates IgE-dependent antigen uptake and presentation to T cells. On macrophages, upon IgE binding and antigen cross-linking induces intracellular killing of parasites through activation of L-Arginine-nitric oxide pathway.|||N- and O-glycosylated.|||There are two kinds of Fc receptors for IgE, which differ in both structure and function: high affinity receptors on basophils and mast cells and low affinity receptors on lymphocytes and monocytes. http://togogenome.org/gene/10090:Sharpin ^@ http://purl.uniprot.org/uniprot/Q91WA6 ^@ Disease Annotation|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17538631, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17538631, PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:17538631, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria. LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin. The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation. Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (By similarity).|||Defects in Sharpin are the cause of chronic proliferative dermatitis (cpdm). Cpdm is a spontaneous mutation causing a chronic proliferative dermatitis phenotype, which is characterized histologically by severe inflammation, eosinophilic dermatitis and defects in secondary lymphoid organ development. Mice also display lower total and cortical bone mineral content and bone mineral density, trabecular and cortical bone volume, and trabecular number. TNF-alpha-induced NF-kappa-B activation is attenuated due to inability of the LUBAC complex to mediate linear ubiquitination.|||Highly expressed in thymus and spleen. Present at high level in splenic B- and T-cells (at protein level).|||Monomer and homodimer (By similarity). Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31 (By similarity). LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits (By similarity). Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner (By similarity). Interacts with EYA1, EYA2, SHANK1 and SHANK3 (via ANK repeats) (PubMed:20956555).|||Synapse|||The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin. Binds preferentially linear polyubiquitin chains and 'Lys-63'-linked polyubiquitin chains over 'Lys-48'-linked polyubiquitin chains. Also binds monoubiquitin (By similarity).|||The Ubiquitin-like domain is required for the interaction with RNF31.|||cytosol http://togogenome.org/gene/10090:Unc13c ^@ http://purl.uniprot.org/uniprot/Q8K0T7 ^@ Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the unc-13 family.|||Contaminating sequence. Sequence of unknown origin in the N- terminal and C-terminal parts.|||Cytoplasm|||Interacts with STX1A and/or STX1B1, VAMP2 and SNAP25.|||May play a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. May be involved in the regulation of synaptic transmission at parallel fiber - Purkinje cell synapses.|||Membrane|||Mutant mice showed no obvious physical or behavioral abnormalities. Some deficiency in motor learning can be observed, compared to wild type, in a motor performance and learning test on a rotating rod, but only at high rotation speed.|||Presynaptic cell membrane|||Restricted to cerebellum, predominantly in the granule cell layer. Almost exclusively present in the molecular layer in which the parallel fiber axons of granule cells terminate on dendrites of Purkinje neurons (at protein level).|||The C2 domains are not involved in calcium-dependent phospholipid binding. http://togogenome.org/gene/10090:Plekha2 ^@ http://purl.uniprot.org/uniprot/Q9ERS5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds MPDZ and PTPN13.|||Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane.|||Cell membrane|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Creb3l4 ^@ http://purl.uniprot.org/uniprot/Q9D2A5 ^@ Caution|||Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:15938716 binds to the UPR element (UPRE) but not to CRE or the NF-kappa-B site. Preferentially binds DNA with to the consensus sequence 5'-T[GT]ACGT[GA][GT]-3' and has transcriptional activation activity from UPRE. According to PubMed:11956138 and to PubMed:16925989 binds to NF-kappa-B site and has transcriptional activation activity from NF-kappa-B-containing regulatory elements.|||Belongs to the bZIP family. ATF subfamily.|||Binds DNA as a dimer (By similarity). Forms a heterodimer with CREM isoform Tau.|||Controlled by regulated intramembrane proteolysis (RIP). Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2). PS1 cleavage may be suppressed by a determinant in the C-terminal region.|||Creb3l4 null-deficient mice show a reduced spermatogenesis but are fertile.|||Endoplasmic reticulum membrane|||Expression is very low in the prepubertal testis (2-5-, 8- and 17-day-old) but becomes abruptly induced in the postpubertal testis (29-day-old), after which expression increased (35- and 60-day-old).|||Major.|||Minor.|||Nucleus|||Predominantly expressed at high levels in testis with isoform 2 being the predominant isoform. Specifically expressed in postmeiotic spermatids and accumulates in the mid/late stage (at protein level). Ubiquitously expressed at low levels.|||Transcriptional activator that may play a role in the unfolded protein response of the testis. Proposed to be involved in spermiogenesis. May be involved in regulating the maturation of sperm head nuclei. Alternatively proposed to be a paternally delivered transcription factor that may function in early zygotic gene activation. Increases the binding of CREM isoform Tau with CRE. The CREM isoform Tau-CREB3L4 heterodimer functions through CRE but not through UPRE and may recruit HIRA to CRE to regulate histone exchange.|||acrosome inner membrane http://togogenome.org/gene/10090:Eif3e ^@ http://purl.uniprot.org/uniprot/P60229|||http://purl.uniprot.org/uniprot/Q3UIG0 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eIF-3 subunit E family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with COPS3, COPS6, COPS7 (COPS7A or COPS7B), EIF4G1, EPAS1, MCM7, NCBP1, PSMC6, TRIM27 and UPF2 (By similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts with BZW2/5MP1 (By similarity).|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with COPS3, COPS6, COPS7 (COPS7A or COPS7B), EIF4G1, EPAS1, MCM7, NCBP1, PSMC6, TRIM27 and UPF2.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway. May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins.|||Cytoplasm|||EIF3E serves as a site for viral integration of mouse mammary tumor virus (MMTV) in mammary tumors. MMTV integration into EIF3E can result in EIF3E truncation and expression of chimeric RNA species which terminate at a cryptic transcription stop signal in the reverse U3 portion of the MMTV long terminal repeat. This causes deregulation of the normal control of mammary epithelial cell growth.|||Nucleus|||PML body|||Phosphorylated upon DNA damage, probably by ATM or ATR.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Vasn ^@ http://purl.uniprot.org/uniprot/Q9CZT5 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Expression begins at 10.5 dpc and increases as development progresses to 17.5 dpc. Expression rises in parallel with the differentiation of vascular smooth muscle cells (VSMCs) of the aorta.|||Interacts with TGFB1, TGFB2 and TGFB3.|||May act as an inhibitor of TGF-beta signaling.|||Membrane|||N-glycosylated.|||Upon retinoic acid-induced differentiation of smooth muscle cells in vitro. http://togogenome.org/gene/10090:Actb ^@ http://purl.uniprot.org/uniprot/B2RRX1|||http://purl.uniprot.org/uniprot/P60710 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (By similarity). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (By similarity). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:23558171, PubMed:25759381). Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity).|||Belongs to the actin family.|||Expressed in the epididymis (at protein level) (PubMed:30659401). Expressed in the kidney (at protein level) (PubMed:31605441).|||ISGylated.|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Methylated at His-73 by SETD3 (PubMed:30626964). Methylation at His-73 is required for smooth muscle contraction of the laboring uterus during delivery (PubMed:30626964).|||Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.|||N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins. In contrast, filament nucleation by the Arp2/3 complex is not affected.|||N-terminal cleavage of acetylated methionine of immature cytoplasmic actin by ACTMAP.|||Nucleus|||Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization (PubMed:23911929). MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization (PubMed:23911929).|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (PubMed:25759381). Each actin can bind to 4 others (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Component of the BAF complex, which includes at least actin (ACTB), ARID1A, ARID1B/BAF250, SMARCA2, SMARCA4/BRG1, MARCB1/BAF47, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more of SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3 (By similarity). Found in a complex with XPO6, Ran, ACTB and PFN1 (By similarity). Component of a complex composed at least of ACTB, AP2M1, AP2A1, AP2A2, MEGF10 and VIM (By similarity). Interacts with XPO6 and EMD (By similarity). Interacts with ERBB2 (By similarity). Interacts with GCSAM (By similarity). Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with TBC1D21 (PubMed:21128978). Interacts with DHX9 (via C-terminus); this interaction is direct and mediates the attachment to nuclear ribonucleoprotein complexes (By similarity). Interacts with FAM107A (PubMed:21969592). Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The filament contains 8 copies of ACTR1A and 1 ACTB (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Mrps18c ^@ http://purl.uniprot.org/uniprot/Q8R2L5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS18 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Mcrip1 ^@ http://purl.uniprot.org/uniprot/Q3UGS4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MCRIP family.|||Interacts (unphosphorylated form, via the PXDLS motif) with CTBP1, competitively inhibiting CTBP-ZEB1 interaction. Interacts with CTBP2. Interacts with MCRIP2. Interacts with DDX6.|||Nucleus|||Phosphorylation by MAPK3/1 (ERK1/2) regulates MCRIP1 binding to CTBP(s).|||Stress granule|||The phosphorylation status of MCRIP1 functions as a molecular switch to regulate epithelial-mesenchymal transition. Unphosphorylated MCRIP1 binds to and inhibits the transcriptional corepressor CTBP(s). When phosphorylated by MAPK/ERK, MCRIP1 releases CTBP(s) resulting in transcriptional silencing of the E-cadherin gene and induction of epithelial-mesenchymal transition.|||Widely expressed (at protein level). http://togogenome.org/gene/10090:Itgam ^@ http://purl.uniprot.org/uniprot/E9Q604|||http://purl.uniprot.org/uniprot/G5E8F1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the integrin alpha chain family.|||Membrane http://togogenome.org/gene/10090:1810037I17Rik ^@ http://purl.uniprot.org/uniprot/Q99M08 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Abhd17c ^@ http://purl.uniprot.org/uniprot/Q8VCV1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. ABHD17 family.|||Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards DLG4/PSD95.|||Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization. Palmitoylation is required for post-synaptic localization and for depalmitoylating activity towards DLG4/PSD95.|||Postsynaptic density membrane|||Recycling endosome membrane|||dendritic spine http://togogenome.org/gene/10090:Gcn1 ^@ http://purl.uniprot.org/uniprot/E9PVA8 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GCN1 family.|||Cytoplasm|||Expressed in the hypothalamus, cortex and hippocampus (PubMed:15937339).|||Interacts with EIF2AK4/GCN2; this interaction stimulates the EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety of stress conditions, such as amino acid depletion, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation (PubMed:24333428). Interacts with IMPACT; this prevents the interaction of GCN1 with EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity (PubMed:15937339, PubMed:22404850). Interacts with RNF14; interaction takes place following ribosome stalling and promotes recruitment of RNF14 (By similarity).|||Perinatal lethality; mice die at the intermediate stage of embryonic development because of severe growth retardation (PubMed:32324833). Tamoxifen-inducible deletion in adult mice leads to transient body weight loss associated with decrease of fat and liver glycogen storage (PubMed:35328622).|||Ribosome collision sensor that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (By similarity). Directly binds to the ribosome and acts as a sentinel for colliding ribosomes: activated following ribosome stalling and promotes recruitment of RNF14, which directly ubiquitinates EEF1A1/eEF1A, leading to its degradation (By similarity). In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein (By similarity). GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of EIF2AK4/GCN2 in response to amino acid starvation (PubMed:15937339, PubMed:24333428, PubMed:32324833). Interaction with EIF2AK4/GCN2 on translating ribosomes stimulates EIF2AK4/GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) (PubMed:24333428, PubMed:32324833). EIF2S1/eIF-2-alpha phosphorylation converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:24333428, PubMed:32324833).|||The RWDBD (RWD-binding domain) region mediates binding to RWD domain-containing proteins, such as EIF2AK4/GCN2, IMPACT and RNF14. http://togogenome.org/gene/10090:Rabgef1 ^@ http://purl.uniprot.org/uniprot/Q9JM13 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Early endosome|||Expressed in the white matter tracts of the cerebellum, the fimbria hippocampi and the corpus callosum.|||Heterodimer with RABEP1. The heterodimer binds RAB4A and RAB5A that have been activated by GTP-binding. Binds TSC2, GGA1, GGA2, GGA3, AP1G1 and AP1G2 (By similarity). Interacts with RAB21, and with 100-fold lower affinity also with RAB22 (By similarity). Interacts with ubiquitinated EGFR (By similarity). Interacts with RGS14; the interaction is GTP-dependent.|||Monoubiquitinated.|||Rab effector protein acting as linker between gamma-adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A (By similarity). Can act as a ubiquitin ligase (By similarity).|||Recycling endosome http://togogenome.org/gene/10090:Ctsg ^@ http://purl.uniprot.org/uniprot/P28293 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Cytoplasmic granule|||In adult, detected only in bone marrow where expression is restricted to a small population of early myeloid cells.|||Inhibited by chymostatin, phenylmethanesulfonyl fluoride and diisopropyl fluorophosphate.|||Lysosome|||Nucleus|||Secreted|||Serine protease with trypsin- and chymotrypsin-like specificity. Also displays antibacterial activity against Gram-negative and Gram-positive bacteria independent of its protease activity. Prefers Phe and Tyr residues in the P1 position of substrates but also cleaves efficiently after Trp and Leu. Shows a preference for negatively charged amino acids in the P2' position and for aliphatic amino acids both upstream and downstream of the cleavage site. Required for recruitment and activation of platelets which is mediated by the F2RL3/PAR4 platelet receptor. Binds reversibly to and stimulates B cells and CD4(+) and CD8(+) T cells. Also binds reversibly to natural killer (NK) cells and enhances NK cell cytotoxicity through its protease activity. Cleaves complement C3 (By similarity). Cleaves vimentin (PubMed:1577012). Cleaves thrombin receptor F2R/PAR1. Cleaves the synovial mucin-type protein PRG4/lubricin. Cleaves and activates IL36G which promotes expression of chemokines CXCL1 and CXLC8 in keratinocytes. Cleaves IL33 into mature forms which have greater activity than the unprocessed form. Cleaves coagulation factor F8 to produce a partially activated form. Also cleaves and activates coagulation factor F10. Cleaves leukocyte cell surface protein SPN/CD43 to releases its extracellular domain and trigger its intramembrane proteolysis by gamma-secretase, releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus. During apoptosis, cleaves SMARCA2/BRM to produce a 160 kDa cleavage product which localizes to the cytosol. Cleaves MBP in B cell lysosomes at '221-Phe-|-Lys-222', degrading the major immunogenic MBP epitope and preventing the activation of MBP-specific autoreactive T cells. Cleaves annexin ANXA1 and antimicrobial peptide CAMP to produce peptides which act on neutrophil N-formyl peptide receptors to enhance the release of CXCL2. Acts as a ligand for the N-formyl peptide receptor FPR1, enhancing phagocyte chemotaxis. Has antibacterial activity against the Gram-negative bacteria N.gonorrhoeae and P.aeruginosa. Likely to act against N.gonorrhoeae by interacting with N.gonorrhoeae penA/PBP2. Exhibits potent antimicrobial activity against the Gram-positive bacterium L.monocytogenes. Has antibacterial activity against the Gram-positive bacterium S.aureus and degrades S.aureus biofilms, allowing polymorphonuclear leukocytes to penetrate the biofilm and phagocytose bacteria. Has antibacterial activity against M.tuberculosis (By similarity).|||cytosol http://togogenome.org/gene/10090:Or14a256 ^@ http://purl.uniprot.org/uniprot/F7CWV4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pmp2 ^@ http://purl.uniprot.org/uniprot/P24526 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Cytoplasm|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||May play a role in lipid transport protein in Schwann cells. May bind cholesterol (By similarity).|||Monomer.|||P2 protein and myelin basic protein together constitute a major fraction of peripheral nervous system myelin protein. http://togogenome.org/gene/10090:Pick1 ^@ http://purl.uniprot.org/uniprot/E9PUZ5|||http://purl.uniprot.org/uniprot/Q8C1W2 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.|||cytoskeleton|||perinuclear region|||synaptosome http://togogenome.org/gene/10090:Gm525 ^@ http://purl.uniprot.org/uniprot/Q3V3I5 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Vps4b ^@ http://purl.uniprot.org/uniprot/P46467|||http://purl.uniprot.org/uniprot/Q3TN07|||http://purl.uniprot.org/uniprot/Q8BM73 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) In conjunction with the ESCRT machinery also appears to function in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (lentiviruses).|||Belongs to the AAA ATPase family.|||Endosome membrane|||High level expression seen in the kidney. It is also expressed in the heart, brain, spleen, lung, liver, skeletal muscle, and testis.|||Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).|||Late endosome membrane|||Membrane|||Proposed to be monomeric or homodimeric in nucleotide-free form and to oligomerize upon binding to ATP to form two stacked hexameric or heptameric rings with a central pore through which ESCRT-III substrates are translocated in an ATP-dependent manner. In vitro, associates on the inside of a helical tubular structure formed by a CHMP2A-CHMP3 polymer. Interacts with CHMP1A, CHMP1B, CHMP4B and CHMP6. Interacts with CHMP2A (PubMed:15173323). Interacts with VPS4A; the interaction suggests a heteromeric assembly with VPS4A (PubMed:12594041). Interacts with VTA1 (By similarity).|||The MIT domain serves as an adapter for ESCRT-III proteins. It forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT interacting motif) helices along the groove between MIT helices 2 and 3 present in a subset of ESCRT-III proteins thus establishing the canonical MIM-MIT interaction. In an extended conformation along the groove between helices 1 and 3, also binds to a type-2 MIT interacting motif (MIM2). http://togogenome.org/gene/10090:Fam234b ^@ http://purl.uniprot.org/uniprot/Q8BYI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM234 family.|||Golgi outpost|||Membrane|||microtubule organizing center http://togogenome.org/gene/10090:Or2d3 ^@ http://purl.uniprot.org/uniprot/K7N662 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wwp2 ^@ http://purl.uniprot.org/uniprot/Q9DBH0 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ A cysteine residue is required for ubiquitin-thioester formation.|||Activated by NDFIP1- and NDFIP2-binding.|||Autoubiquitinated. Ubiquitinated by the SCF(FBXL15) complex, leading to its degradation by the proteasome (By similarity).|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; regulates POU5F1 protein level during differentiation of embryonal carcinoma cells (ECCs) but not in undifferentiated ECCs and embryonic stem cells (ESCs). Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation.|||Interacts with SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2 and ATN1. Interacts with ERBB4, NDFIP1 and NDFIP2. Interacts with ARRDC4 (By similarity). Interacts with POU5F1, RBP1, EGR2 and SLC11A2. Interacts (via WW domains) with ARRDC1 (via PPxY motifs); ubiquitinates ARRDC1 (By similarity). Interacts (via WW domains) with ARRDC2 and ARRDC3 (By similarity).|||Nucleus|||The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.|||The WW domains mediate interaction with PPxY motif-containing proteins. http://togogenome.org/gene/10090:Sh3bgrl3 ^@ http://purl.uniprot.org/uniprot/Q91VW3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SH3BGR family.|||Could act as a modulator of glutaredoxin biological activity (By similarity). May play a role in cytoskeleton organization (By similarity).|||Homodimer (PubMed:15120624). Interacts with MYO1C (via its IQ motifs); the interaction is dependent on calcium and takes place at membrane ruffles (By similarity).|||May be glycosylated.|||Nucleus|||cytosol|||ruffle membrane http://togogenome.org/gene/10090:Aldh16a1 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSU0|||http://purl.uniprot.org/uniprot/Q571I9 ^@ Caution|||Similarity|||Subunit ^@ Belongs to the aldehyde dehydrogenase family.|||Interacts with SPG21.|||The active site cysteine and glutamate residues are not conserved in this protein. Its activity is therefore unsure. http://togogenome.org/gene/10090:Dnajc3 ^@ http://purl.uniprot.org/uniprot/Q91YW3 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to misfolded proteins is mediated by a hydrophobic patch forming a large groove within the first two TPR repeats.|||Endoplasmic reticulum|||Interacts with EIF2AK4/GCN2; this interaction occurs under endoplasmic reticulum (ER) stress, hypothermic and amino acid starving stress conditions and inhibits EIF2AK4/GCN2 kinase activity (PubMed:25329545). Interacts with EIF2AK3 (PubMed:12446838). Interacts with EIF2AK2. Forms a trimeric complex with DNAJB1 and HSPA8. Interacts with THAP12 (By similarity).|||Involved in the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Acts as a negative regulator of the EIF2AK4/GCN2 kinase activity by preventing the phosphorylation of eIF-2-alpha at 'Ser-52' and hence attenuating general protein synthesis under ER stress, hypothermic and amino acid starving stress conditions (PubMed:25329545). Co-chaperone of HSPA8/HSC70, it stimulates its ATPase activity. May inhibit both the autophosphorylation of EIF2AK2/PKR and the ability of EIF2AK2 to catalyze phosphorylation of the EIF2A. May inhibit EIF2AK3/PERK activity (By similarity).|||The J domain mediates interaction with HSPA8.|||Up-regulated during an endoplasmic reticulum stress.|||Widely expressed, with high level in the liver. http://togogenome.org/gene/10090:Prnp ^@ http://purl.uniprot.org/uniprot/P04925|||http://purl.uniprot.org/uniprot/Q3UG89|||http://purl.uniprot.org/uniprot/Q4FJQ7 ^@ Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the prion family.|||Cell membrane|||Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization.|||Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.|||Golgi apparatus|||Highly expressed in the brain, lung, kidney and heart. Expressed at low levels in the liver and spleen.|||Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis through acting as an agonist for ADGRG6 receptor. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (By similarity). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (PubMed:12732622, PubMed:16492732, PubMed:19242475, PubMed:19568430).|||Membrane|||Monomer and homodimer. Has a tendency to aggregate into amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Soluble oligomers may represent an intermediate stage on the path to fibril formation. Copper binding may promote oligomerization. Interacts with GRB2, APP, ERI3/PRNPIP and SYN1 (PubMed:11571277). Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement (By similarity). Interacts with APP. Interacts with KIAA1191 (By similarity). Interacts with ADGRG6 (PubMed:27501152).|||N-glycosylated.|||No visible phenotype. Mice develop chronic demyelinating polyneuropathy after 60 weeks. Mice show abnormally low iron levels throughout the body, and are mildly anemic. Iron accumulates in duodenum enterocytes, suggesting impaired transport from the intestine to the blood. Mice deficient for both Prnd and Prnp have the same phenotype as mice lacking Prnd; they are born at the expected Mendelian rate and appear grossly normal and healthy (PubMed:15161660, PubMed:15007175). Females are fertile, but males deficient for both Prnd and Prnp are sterile, in spite of normal mating behavior (PubMed:15161660, PubMed:15007175). Male sterility is due to impaired acrosome reaction (PubMed:15161660). Mutant sperm are able to fertilize oocytes in vitro, but many of the resulting embryos die before the morula stage (PubMed:15161660). Mutant sperm cells have elevated levels of DNA damage and DNA strand breaks, and this may be the cause for embryonic lethality (PubMed:15161660). Aging mice deficient for both Prnd and Prnp do not display loss of cerebellar Purkinje cells or develop ataxia, and do not develop neurological defects (PubMed:15007175).|||The normal, monomeric form has a mainly alpha-helical structure. The disease-associated, protease-resistant form forms amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization. http://togogenome.org/gene/10090:Or4c124 ^@ http://purl.uniprot.org/uniprot/Q8VEX7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arhgef12 ^@ http://purl.uniprot.org/uniprot/F8VQN6 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Membrane http://togogenome.org/gene/10090:Utp23 ^@ http://purl.uniprot.org/uniprot/Q9CX11 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UTP23/FCF1 family. UTP23 subfamily.|||Involved in rRNA-processing and ribosome biogenesis.|||nucleolus http://togogenome.org/gene/10090:Or8g30 ^@ http://purl.uniprot.org/uniprot/Q9EQ95 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Skap1 ^@ http://purl.uniprot.org/uniprot/B2RWZ1|||http://purl.uniprot.org/uniprot/Q3UUV5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKAP family.|||Cell membrane|||Cytoplasm|||Homodimer (By similarity). Interacts with FYN (PubMed:12681493). Interacts with PTPRC (By similarity). Interacts with GRB2 when phosphorylated on Tyr-268 (By similarity). Interacts with FYB1, which is required for SKAP2 protein stability (By similarity). Interacts with FYB1, which is required for SKAP2 protein stability (By similarity). Part of a complex consisting of SKAP1, FYB1 and CLNK (PubMed:12681493). Interacts with RASGRP1 (By similarity). Interacts with FYB2 (By similarity).|||Nucleus|||Phosphorylated on tyrosines. Phosphorylation by FYN on Tyr-268 is required for GRB2 interaction (By similarity). Phosphorylation by FYN on Tyr-291 abolishes interaction with FYB1. Tyr-237 is dephosphorylated by PTPRC (By similarity).|||Positively regulates T-cell receptor signaling by enhancing the MAP kinase pathway (By similarity). Required for optimal conjugation between T-cells and antigen-presenting cells by promoting the clustering of integrin ITGAL on the surface of T-cells (By similarity). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (PubMed:12681493).|||The SH3 domain interacts with FYB1. http://togogenome.org/gene/10090:Ccdc89 ^@ http://purl.uniprot.org/uniprot/Q9DA73 ^@ Developmental Stage|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC89 family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||Expressed in adults but not embryos.|||Expression is restricted to the adult testis, where localization is almost exclusive to round spermatids.|||Interacts with HEY1.|||Nucleus http://togogenome.org/gene/10090:Vmn2r66 ^@ http://purl.uniprot.org/uniprot/K7N6R9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nr2c2ap ^@ http://purl.uniprot.org/uniprot/Q3TV70 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NR2C2AP family.|||Interacts with NR2C2/TR4.|||May act as a repressor of NR2C2-mediated transactivation by suppressing the binding between NR2C2/TR4 and the TR4-response element in target genes.|||Nucleus http://togogenome.org/gene/10090:Snai3 ^@ http://purl.uniprot.org/uniprot/Q9QY31 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the snail C2H2-type zinc-finger protein family.|||Binds E-box via C2H2-type zinc finger domain.|||Expressed at 7 dpc, higher expression observed in stages 15 dpc and 18 dpc.|||Highly expressed in skeletal muscle and thymus. Lower expression in heart, lung and spleen.|||Nucleus|||Seems to inhibit myoblast differentiation. Transcriptional repressor of E-box-dependent transactivation of downstream myogenic bHLHs genes. Binds preferentially to the canonical E-box sequences 5'-CAGGTG-3' and 5'-CACCTG-3'. http://togogenome.org/gene/10090:Ermap ^@ http://purl.uniprot.org/uniprot/A2A7P7|||http://purl.uniprot.org/uniprot/Q9JLN5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Cell membrane|||Cytoplasm|||Expressed in spleen and bone marrow.|||First detected at 11 dpc. Expressed in fetal liver at 12.5 dpc and 13.5 dpc.|||Glycosylated.|||Membrane|||Possible role as a cell-adhesion or receptor molecule of erythroid cells. http://togogenome.org/gene/10090:Chd2 ^@ http://purl.uniprot.org/uniprot/E9PZM4 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ DNA-binding helicase that specifically binds to the promoter of target genes, leading to chromatin remodeling, possibly by promoting deposition of histone H3.3. Involved in myogenesis via interaction with MYOD1: binds to myogenic gene regulatory sequences and mediates incorporation of histone H3.3 prior to the onset of myogenic gene expression, promoting their expression.|||Growth delay late in embryogenesis and perinatal lethality (PubMed:16810678). Heterozygous mice show decreased neonatal viability. Heterozygous mice display glomerulopathy, proteinuria and impaired kidney function. Glomerulopathy may be associated with anemia (PubMed:19142019). Heterozygous mutant also show increased extramedullary hematopoiesis and susceptibility to lymphomas, with defects in hematopoietic stem cell differentiation (PubMed:19137022).|||Interacts with MYOD1. Interacts with histone H3.3.|||Nucleus|||The CHD1 helical C-terminal domain (CHCT) may bind DNA and nucleosomes.|||Widely expressed. http://togogenome.org/gene/10090:Sult2a6 ^@ http://purl.uniprot.org/uniprot/B2RVI8 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Syce2 ^@ http://purl.uniprot.org/uniprot/Q505B8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SYCE family.|||Chromosome|||Expressed in ovary, embryo, spleen, thymus, brain, kidney, epididymis, heart and liver at 14 dpc and in oocytes at 18 dpc.|||Homodimer (PubMed:15944401). Found in a complex with SYCP1 and SYCE1 (PubMed:15944401). Interacts with SYCP1 and SYCE1 (PubMed:15944401). Interacts with SYCE3 (PubMed:21637789). Interacts with TEX12 (PubMed:16968740).|||Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase (PubMed:15944401). Requires SYCP1 in order to be incorporated into the central element (PubMed:15944401, PubMed:16968740). May have a role in the synaptonemal complex assembly, stabilization and recombination (PubMed:15944401).|||Meiotic cells (at protein level). Expressed in the ovary and testis.|||Nucleus http://togogenome.org/gene/10090:Gpx6 ^@ http://purl.uniprot.org/uniprot/Q91WR8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glutathione peroxidase family.|||Secreted http://togogenome.org/gene/10090:Dnttip1 ^@ http://purl.uniprot.org/uniprot/Q3THA4|||http://purl.uniprot.org/uniprot/Q99LB0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Increases DNTT terminal deoxynucleotidyltransferase activity (in vitro). Also acts as a transcriptional regulator, binding to the consensus sequence 5'-GNTGCATG-3' following an AT-tract. Associates with RAB20 promoter and positively regulates its transcription. Binds DNA and nucleosomes; may recruit HDAC1 complexes to nucleosomes or naked DNA.|||Monomer and homodimer (By similarity). A minor proportion may form homotrimers (By similarity). Interacts with ZNF541 (PubMed:18849567). Interacts with the terminal deoxynucleotidyltransferase DNTT (By similarity). Interacts with TRERF1 (By similarity). Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain (By similarity). Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 (By similarity). Identified in a complex with KCTD19, HDAC1, HDAC2 and ZNF541 (PubMed:34075040, PubMed:35341968).|||Nucleus|||The C-terminal domain mediates interaction with DNA and nucleosomes. It contains a HTH motif that mediates recognition of the consensus sequence.|||The N-terminal domain mediates dimerization. http://togogenome.org/gene/10090:Limd1 ^@ http://purl.uniprot.org/uniprot/Q9QXD8 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation.|||Belongs to the zyxin/ajuba family.|||Cytoplasm|||Interacts with SQSTM1 and RB1. Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, EGLN1/PHD2, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM zinc-binding 2) with VHL. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2 (By similarity). Interacts (via LIM domains) with SNAI1 (via SNAG domain), SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain). Found in a complex with TRAF6, PRKCZ and SQSTM1. Interacts (via LIM domains) with TRAF6.|||Nucleus|||P-body|||Phosphorylated during mitosis.|||Ubiquitous.|||Up-regulated during osteoclast differentiation.|||adherens junction|||focal adhesion http://togogenome.org/gene/10090:Jag1 ^@ http://purl.uniprot.org/uniprot/Q3UVN4|||http://purl.uniprot.org/uniprot/Q9QXX0 ^@ Caution|||Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.75-9.75 dpc expression was detected in structures that include those destined to contribute to the cardiovascular system of the adult heart. Expression was also detected in the mesencephalon and rhombencephalon.|||Cell membrane|||Interacts with NOTCH1, NOTCH2 and NOTCH3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). May regulate fibroblast growth factor-induced angiogenesis.|||Membrane|||Putative Notch ligand involved in the mediation of Notch signaling.|||The DSL domain is indispensable and sufficient for binding to NOTCH2.|||Widely expressed in many tissues, with highest expression in brain, heart, muscle and thymus. http://togogenome.org/gene/10090:Or2n1 ^@ http://purl.uniprot.org/uniprot/Q8VG95 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmigd1 ^@ http://purl.uniprot.org/uniprot/Q9D7L8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Homodimer.|||May control cell-cell adhesion, cell migration and proliferation, cell morphology, and protects renal epithelial cells from oxidative cell injury to promote cell survival.|||N-glycosylated. http://togogenome.org/gene/10090:Lsm1 ^@ http://purl.uniprot.org/uniprot/Q544C9|||http://purl.uniprot.org/uniprot/Q8VC85 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Cytoplasm|||Interacts with SLBP; interaction with SLBP occurs when histone mRNA is being rapidly degraded during the S phase (By similarity). LSm subunits form a heteromer with a donut shape (By similarity).|||Interacts with SLBP; interaction with SLBP occurs when histone mRNA is being rapidly degraded during the S phase. LSm subunits form a heteromer with a donut shape.|||P-body|||Plays a role in the degradation of histone mRNAs, the only eukaryotic mRNAs that are not polyadenylated (By similarity). Probably also part of an LSm subunits-containing complex involved in the general process of mRNA degradation (By similarity).|||Plays a role in the degradation of histone mRNAs, the only eukaryotic mRNAs that are not polyadenylated. Probably also part of an LSm subunits-containing complex involved in the general process of mRNA degradation. http://togogenome.org/gene/10090:Slc6a4 ^@ http://purl.uniprot.org/uniprot/Q60857 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily.|||Cell membrane|||Endomembrane system|||Endosome membrane|||Expressed in a circadian manner in the midbrain with a higher level expression seen during the dark phase (at protein level).|||Expressed in the lung, midbrain and brainstem regions (PubMed:9037532). Expressed in brainstem raphe neurons (PubMed:25600870).|||Expressed in the uncrossed ipsilateral retinal ganglion cells (iRGCs) of the peripheral ventrotemporal (VT) region segment in the retina at 16.5 dpc (PubMed:20676059). Expressed during early postnatal brain development in neurons of brainstem and ventrobasal complex (VB) nuclei, including thalamic VB, dorso-lateral geniculate (DLG) nucleus neurons and hippocampal neurons. Expressed in the somatosensory cortex and the brainstem at postnatal day 7 (at protein level) (PubMed:25600870).|||Monomer or homooligomer (By similarity). Interacts (via C-terminus) with SCAMP2; the interaction is direct and retains transporter molecules intracellularly. Interacts with filamentous actin and STX1A (By similarity). Interacts (via the N-terminus) with STX1A (via the H3 domain); this interaction regulates SLC4A6 channel conductance (By similarity). Interacts with SEC23A, SEC24C and PATJ. Interacts with NOS1; the interaction may diminish the cell surface localization of SERT in the brain and, correspondingly, reduce serotonin reuptake (PubMed:17452640). Interacts with TGFB1I1 (PubMed:16803896). Interacts with ITGAV:ITGB3 (PubMed:29038237). Interacts (via C-terminus) with ITGB3; this interaction regulates SLC6A4 trafficking (By similarity).|||Mutant mice are born at the expected Mendelian rate. Knockdown results in loss of serotonin uptake in synaptosomes of brainstem and cortex, abnormal barrel cortex development, enteric nervous system hyperplasia and reduced peristaltic reflexes.|||Phosphorylation at Thr-276 increases 5-HT uptake and is required for cGMP-mediated SERT regulation.|||Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:9037532, PubMed:9547354) (By similarity). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (PubMed:25600870, PubMed:9547354). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (PubMed:27111230). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:9037532, PubMed:9547354) (By similarity). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity).|||Synapse|||This protein is the target of psychomotor stimulants such as amphetamines or cocaine.|||focal adhesion|||neuron projection http://togogenome.org/gene/10090:Opa3 ^@ http://purl.uniprot.org/uniprot/Q505D7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the OPA3 family.|||May play some role in mitochondrial processes.|||Mitochondrion http://togogenome.org/gene/10090:Amy2a3 ^@ http://purl.uniprot.org/uniprot/P00688 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 13 family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 1 Cl(-) ion per subunit.|||Monomer.|||extracellular space http://togogenome.org/gene/10090:Slfn8 ^@ http://purl.uniprot.org/uniprot/B1ARD8 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Schlafen family. Subgroup III subfamily.|||Can also use Mn(2+).|||Cytoplasm|||Endoribonuclease that cleaves tRNAs and rRNAs (PubMed:29563550). Cleaves tRNAs 11 nucleotides from the 3'-terminus at the acceptor stem (PubMed:29563550). May be involved in immune system via regulation of inflammation (PubMed:29528433).|||In T-cells, expressed at relatively constant levels during development: expressed in immature CD3(-)CD4(-)CD8(-) T-cells (DN stage), in CD4(+)CD8(+) double-positive stage (DP) and mature CD4(+) or CD8(+) thymocytes. Expression is slightly reduced at the DP stage.|||Induced following infection.|||No visible phenotype in normal conditions. Mice are resistant in experimental autoimmune encephalomyelitis (EAE) model, a T-cell-mediated autoimmune model. The expression of pro-inflammatory mediators is severely reduced in EAE. No dysfunction of T-cells, or other leukocytes is detected.|||Shows a pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs. http://togogenome.org/gene/10090:Uqcc2 ^@ http://purl.uniprot.org/uniprot/Q9CQY6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with UQCC1 (By similarity). Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508). Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508). Forms a complex, named COMA, composed of UQCC1, UQCC2 and UQCC4; activates MT-CYB translation (PubMed:35977508). Forms a complex, named COMC, composed of UQCC1, UQCC2; UQCC3 and UQCC4; mediates MT-CYB hemylation and association with the first nuclear-encoded CIII subunit UQCRQ (PubMed:35977508).|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||Mitochondrion matrix|||Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex). Plays a role in the modulation of respiratory chain activities such as oxygen consumption and ATP production and via its modulation of the respiratory chain activity can regulate skeletal muscle differentiation and insulin secretion by pancreatic beta-cells. Involved in cytochrome b translation and/or stability.|||Widely expressed with highest levels in brain, liver, kidney, heart, skeletal muscle, thymus, testis and pancreas (at protein level).|||mitochondrion nucleoid http://togogenome.org/gene/10090:Pls1 ^@ http://purl.uniprot.org/uniprot/Q3V0K9 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-bundling protein. In the inner ear, it is required for stereocilia formation. Mediates liquid packing of actin filaments that is necessary for stereocilia to grow to their proper dimensions (PubMed:27811163).|||Cytoplasm|||In the inner ear, it is expressed in the organ of Corti (PubMed:25124451). Abundant in the utricle (at protein level) (PubMed:27811163).|||Knockout animals have a progressive form of hearing loss at all frequencies. Hearing loss is moderate in young adult mice, progresses to severe deafness with age, and is associated with defects in stereocilia morphology. Stereocilia are shorter and narrower than those of wild-type mice.|||Monomer.|||Phosphorylated.|||stereocilium http://togogenome.org/gene/10090:1700012B09Rik ^@ http://purl.uniprot.org/uniprot/Q9DAE7 ^@ Developmental Stage|||Disruption Phenotype|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the developing fetal lung epithelium, embryonic ventral node and developing brain (at protein level) (PubMed:28666954, PubMed:27914912).|||Expression is activated by FOXJ1 and NOTO.|||Mice exhibited no impaired function of motile cilia or non-motile cilia.|||Predominantly expressed in tissues containing motile cilia (PubMed:28666954, PubMed:27914912). Also expressed in non-motile ciliated adult olfactory bulbs (PubMed:28666954).|||cilium basal body http://togogenome.org/gene/10090:Lgsn ^@ http://purl.uniprot.org/uniprot/Q8CIX8 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the glutamine synthetase family.|||Dodecamer. Interacts with BFSP2 and VIM.|||Expressed in lens.|||May act as a component of the cytoskeleton or as a chaperone for the reorganization of intermediate filament proteins during terminal differentiation in the lens. Does not seem to have enzymatic activity. http://togogenome.org/gene/10090:Aspm ^@ http://purl.uniprot.org/uniprot/Q8CJ27 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed during cerebral cortical neurogenesis, specifically in the cerebral cortical ventricular zone at 14.5 dpc and 16.5 dpc. Expression is greatly reduced by the day of birth (P0), when neurogenesis in the cortical ventricular zone is completed and gliogenesis is increased. Expression is limited to rare scattered cells in the neocortex by postnatal day 9 (P9).|||Expressed in fetal brain, peripheral nervous system, liver and spleen. In the adult, expressed exclusively in testis, ovary and spleen.|||Interacts with KATNA1 and KATNB1; katanin complex formation KATNA1:KATNB1 is required for the association.|||Involved in mitotic spindle regulation and coordination of mitotic processes. The function in regulating microtubule dynamics at spindle poles including spindle orientation, astral microtubule density and poleward microtubule flux seem to depend on its association with the katanin complex formed by KATNA1 and KATNB1. Enhances the microtubule lattice severing activity of KATNA1 by recruiting the katanin complex to microtubules. Can block microtubule minus-end growth and reversely this function can be enhanced by the katanin complex (PubMed:28436967). May have a preferential role in regulating neurogenesis.|||Nucleus|||spindle http://togogenome.org/gene/10090:Gpr108 ^@ http://purl.uniprot.org/uniprot/Q91WD0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ (Microbial infection) N- and C-terminal domains are essential for mediating AAV transduction.|||(Microbial infection) Plays an essential function in adeno-associated virus (AAV) transduction, across multiple serotypes except AAV5. May play a critical role in mediating the endosomal virus escape or in the AAV virions trafficking from endosomes to the nucleus.|||Belongs to the LU7TM family.|||Deficient mice are viable and fertile and exhibit normal Mendelian segregation, however deficient mice exhibit increased LPS-induced mortality. TLR-mediated pro-inflammatory signaling are increased in embryonic fibroblasts and macrophages from Gpr108 deficient mice (PubMed:30332431). Depending on the AAV serotype used, 10-fold to 100-fold reduced expression for AAV is observed in Gpr108 knockout mice following retro-orbital administration (PubMed:31784416).|||Golgi apparatus membrane|||High expression in spleen, lung, stomach, large and small intestine, and thymus.|||May play a role in intracellular immune modulation by activating NF-kappaB response and attenuating Toll-like-receptor response.|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Vsx2 ^@ http://purl.uniprot.org/uniprot/Q61412|||http://purl.uniprot.org/uniprot/Q6PDC1|||http://purl.uniprot.org/uniprot/Q80WF9 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator through binding to DNA at the consensus sequence 5'-[TC]TAATT[AG][AG]-3' upstream of gene promoters (PubMed:17919464, PubMed:18539116). Plays a significant role in the specification and morphogenesis of the sensory retina (PubMed:8630490). May play a role in specification of V2a interneurons during spinal cord development (PubMed:18539116). Mediates differentiation of V2a interneurons by repression of motor neuron gene transcription, via competitively binding to response elements that are activated by the ISL1-LHX3 complex, such as VSX1 and MNX1 (PubMed:17919464, PubMed:27477290, PubMed:18539116). Acts as a positive transcriptional regulator of NXNL1; regulation is significantly increased in synergy with VSX1 (PubMed:19843539). Acts as a negative transcriptional regulator of MITF (PubMed:23028343). Represses SAG transcription by competitive inhibition of ISL1-LHX3 response elements (By similarity). Binds to the photoreceptor conserved element-1 (PCE-1) in the promoter of rod photoreceptor arrestin SAG and acts as a transcriptional repressor (PubMed:16236706). Involved in the development of retinal ganglion cells (RGCs) which leads to release of SHH by RGCs, promoting Hedgehog signaling and subsequent proliferation of retinal progenitor cells (PubMed:18417110). Participates in the development of the cells of the inner nuclear layer, by promoting postnatal differentiation of bipolar cells with a comparable inhibition of rod cell differentiation (PubMed:8630490, PubMed:16547132). May play a role in the maintenance of neural retina identity during development by regulation of canonical Wnt genes and CTNNB1 localization, suggesting a role in the regulation of canonical Wnt signaling (By similarity).|||Belongs to the paired homeobox family.|||Defects in Vsx2 are the cause of ocular retardation (OR(J)), a mouse disease characterized by microphthalmia, progressive destruction of the retina, and absence of the optic nerve. The OR(J) mutation is due to an OCHR (STOP) mutation.|||Detected by embryonic day 25, by which time the optic cup has formed and the ganglion cell layer can be distinguished. A rapid increase to levels 3- to 4-fold greater than those seen in adult retina occurs in the period from birth (P0) to postnatal day 6 (P6). During this interval, the horizontal, bipolar, amacrine, and cone cells arise from the neuroretinal layer, the inner nuclear layer, and outer nuclear layer separate, and the outer plexiform layer begins to form. Levels begin to decrease by P8, when the rod outer segments are Still differentiating, and reaches its lowest levels in adult retina.|||Expressed in the retina (at protein level) (PubMed:8630490, PubMed:16547132, PubMed:17919464, PubMed:18417110, PubMed:19843539, PubMed:23028343). Expressed throughout the anterior optic vesicle and all neuroblasts of the optic cup (at protein level) (PubMed:8630490). In the mature and postnatal retina is restricted to the inner nuclear layer, in which its expression decreases from the outer to the inner margin (at protein level) (PubMed:8630490, PubMed:17919464, PubMed:19843539). Also detected in regions of the developing thalamus, hindbrain, and ventral spinal cord (PubMed:8630490).|||Interacts with MITF.|||Nucleus|||RNAi-mediated knockdown in the retina of newborn mice results in an increase in the number of photoreceptor cells as a result of a decrease in the number of bipolar cells and a comparable increase in rod cells at postnatal day 21. http://togogenome.org/gene/10090:Rhob ^@ http://purl.uniprot.org/uniprot/P62746 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Binds ROCK1 and ROCK2. Also binds PKN1/PRK1. Interacts with ARGGEF3 (By similarity). Interacts with RTKN (PubMed:8662891). Interacts with AKAP13. Interacts with RIPOR1 (By similarity).|||By UV irradiation, N-methyl-N-nitrosourea, cisplatin, cyclohexamide and serum stimulation.|||Cell membrane|||Cleavage furrow|||Late endosome membrane|||Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.|||Nucleus|||Prenylation specifies the subcellular location of RHOB. The farnesylated form is localized to the plasma membrane while the geranylgeranylated form is localized to the endosome (By similarity). http://togogenome.org/gene/10090:Cldn9 ^@ http://purl.uniprot.org/uniprot/Q9Z0S7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the claudin family.|||Cell membrane|||Interacts with CLDN1, CD81 and OCLN.|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Or2aj5 ^@ http://purl.uniprot.org/uniprot/Q8VGL6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hjv ^@ http://purl.uniprot.org/uniprot/Q7TQ32 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a bone morphogenetic protein (BMP) coreceptor. Through enhancement of BMP signaling regulates hepcidin (HAMP) expression and regulates iron homeostasis.|||Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds. Also proteolytically processed by TMPRSS6, several fragments being released in the extracellular space; regulates HJV activity in BMP signaling and thefore iron homeostasis.|||Belongs to the repulsive guidance molecule (RGM) family.|||Cell membrane|||Expressed at low levels in somite derived structures. In the developing eye, marked the ocular musculature. Expressed in all differentiating muscles of the limb and the body wall, but not in migrating muscle precursor cells. Not detected in the nervous system, either at 9.5 dpc or at any stage later during development.|||Interacts with BMP2 and BMP4 (PubMed:16604073). Interacts with BMP6 (PubMed:19252486). Interacts with BMPR1B (By similarity). Interacts with TMPRSS6 (By similarity).|||Muscle cell lineage. http://togogenome.org/gene/10090:Tsku ^@ http://purl.uniprot.org/uniprot/Q8CBR6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By endoplasmic reticulum stress and inflammation (PubMed:31391339). Up-regulated in response to high-fat diet and this is reversed by return to a normal diet (PubMed:30595550, PubMed:31391339).|||Contributes to various developmental events and other processes such as wound healing and cholesterol homeostasis through its interactions with multiple signaling pathways (PubMed:21856951, PubMed:22995554, PubMed:25159578, PubMed:31391339). Wnt signaling inhibitor which competes with WNT2B for binding to Wnt receptor FZD4 and represses WNT2B-dependent development of the peripheral eye (PubMed:21856951). Plays a role in regulating the hair cycle by controlling TGFB1 signaling (PubMed:22995554). Required for the development of the anterior commissure in the brain by inhibiting neurite outgrowth (PubMed:21055390, PubMed:23206892). Essential for terminal differentiation of hippocampal neural stem cells (PubMed:31983064). Plays a role in regulating bone elongation and bone mass by modulating growth plate chondrocyte function and overall body size (PubMed:30271858). Required for development of the inner ear through its involvement in stereocilia formation in inner hair cells (PubMed:32127020). Facilitates wound healing by inhibiting secretion of TGFB1 from macrophages which prevents myofibroblast differentiation, maintaining inflammatory cell quiescence (PubMed:25159578). Plays a role in cholesterol homeostasis by reducing circulating high-density lipoprotein cholesterol, lowering cholesterol efflux capacity and decreasing cholesterol-to-bile acid conversion in the liver (PubMed:31391339). In one study, shown to negatively regulate sympathetic innervation in brown fat, leading to reduced energy expenditure (PubMed:31535079). In another study, shown not to affect brown fat thermogenic capacity, body weight gain or glucose homeostasis (PubMed:31767170).|||During the hair cycle, expression is down-regulated at the first telogen stage and is up-regulated at the secondary anagen stage.|||Expansion of the ciliary body and up-regulation of Wnt2b and Fzd4 expression in the developing peripheral eye (PubMed:21856951). Delayed hair cycle with down-regulation of Tgfb1 throughout the cycle and low levels of phosphorylated Smad2/3 (PubMed:22995554). Failure of the axons of the anterior and posterior parts of the anterior commissure (AC) to cross the midline, leading to an almost total absence of the AC in adults (PubMed:21055390, PubMed:23206892). Reduced size of hippocampus and dentate gyrus (DG), increased number of neural stem cells (NSCs) in the DG at P15, altered ratio of proliferating and quiescent NSCs with an increase in the number of proliferating NSCs in the DG at P15, and abnormal terminal differentiation of NSCs (PubMed:31983064). Decreased weight and short stature due to decreased longitudinal bone growth coupled with low bone mass (PubMed:30271858). Shortened and morphologically abnormal growth plates and abnormal expression of chondrogenic marker genes (PubMed:30271858). Formation of abnormally short and dislocated stereocilia in the inner hair cells of the ear and hearing loss (PubMed:32127020). Reduced cochlear expression of Sox2 and translocation of Sox2 from the nucleus to the cytoplasm in spiral ganglion cells (SGCs) at P0 (PubMed:32127020). Redistribution of Bmp4 with diminished expression in the outer sulcus and sparse distribution around the cochlear epithelium (PubMed:32127020). Reduced number of SGCs at the cochlear basal turn (PubMed:32127020). Excess wound inflammation with up-regulation of Tgfb1, Stat3 and Il6 during wound healing (PubMed:25159578). Reduced body size, increased levels of circulating high-density lipoprotein cholesterol and increased cholesterol efflux (PubMed:31391339). Some studues showed increased sympathetic innervation and norepinephrine release in adipose tissue, leading to enhanced adrenergic signaling and thermogenesis, attenuation of brown fat whitening and protection from diet-induced obesity (PubMed:31535079, PubMed:30595550). Another study found no effect on brown fat thermogenic capacity, protection from diet-induced obesity or glucose homeostasis (PubMed:31767170). Double knockout of Tsku and Draxi results in a higher frequency of AC defects than single knockout of either Tsku or Draxi (PubMed:23206892).|||Expressed in macrophages in inflamed wounds with wound expression starting 2 days post-wounding (dpw) (at protein level) (PubMed:25159578). At 7 dpw, expressed from epidermis and extracellular matrix in the wound edge to neoepidermis and granulation tissue and in panniculus carnosus under the granulation tissue (at protein level) (PubMed:25159578). After fibrosis, disappears in the dermal area at 11 dpw (at protein level) (PubMed:25159578). Expressed in the hair follicle during morphogenesis and the hair cycle (at protein level) (PubMed:22995554). In embryonic brain, strong expression in the olfactory bulb, anterior olfactory nucleus, neocortex, piriform cortex, glial wedge, midline zipper glia, indusium griseum and the area surrounding the anterior commissure (AC) but not on AC axons (at protein level) (PubMed:23206892). In the adult eye, expressed in retinal layers, lens epithelium, and ciliary body where it is expressed predominantly in the inner non-pigmented layer (PubMed:21856951). Expressed in almost all brain regions in the embryo, in the cortex and the lateral ventricle at P0 and is restricted to the subventricular zone and lateral nucleus of the amygdala in adults (PubMed:21055390). Prominent expression in hippocampal regions from early postnatal stages until postnatal day 15 and gradually declines at later stages (PubMed:31983064). Expressed in almost all bone regions in the femurs of juveniles (PubMed:30271858). In the inner ear, accumulates in nonprosensory regions during early embryonic stages and in both nonprosensory and prosensory regions in late embryonic stages (PubMed:32127020). In the adult ear, expressed in the organ of Corti, spiral ganglion cells, and the stria vascularis (PubMed:32127020). Highly expressed in the liver where it is detected primarily in hepatocytes but not in non-parenchymal cells (PubMed:31535079).|||Interacts with FZD4 (via FZ domain); competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (PubMed:21856951). Interacts with TGFB1; the interaction contributes to regulation of the hair cycle (PubMed:22995554). Interacts with netrin (PubMed:23206892). Interacts with CCN2 (PubMed:30232710).|||Secreted|||This factor is named 'Tsukushi' because its expression pattern in chick embryos is similar to the shape of the Japanese horsetail plant, tsukushi. http://togogenome.org/gene/10090:Map3k11 ^@ http://purl.uniprot.org/uniprot/Q80XI6 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle (By similarity).|||Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation. Thr-278 is likely to be the main autophosphorylation site. Phosphorylation of Ser-556 and Ser-557 is induced by CDC42 (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Homodimer; undergoes dimerization during activation. Interacts with MAP2K4/MKK4 and MAP2K7/MKK7 (By similarity). Found in a complex with SH3RF1, RAC1, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642).|||Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation.|||centrosome http://togogenome.org/gene/10090:Hnf4g ^@ http://purl.uniprot.org/uniprot/Q059V1|||http://purl.uniprot.org/uniprot/Q3UP48|||http://purl.uniprot.org/uniprot/Q9WUU6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Nucleus|||Transcription factor. Has a lower transcription activation potential than HNF4-alpha (By similarity). http://togogenome.org/gene/10090:Pgap3 ^@ http://purl.uniprot.org/uniprot/A2A559 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PGAP3 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchors proteins. Required for phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI (By similarity). http://togogenome.org/gene/10090:Or8h8 ^@ http://purl.uniprot.org/uniprot/A2AVB0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zscan2 ^@ http://purl.uniprot.org/uniprot/Q07230 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||In the adult, predominantly found in spermatids. Also present in the embryo.|||May be involved in transcriptional regulation during the post-meiotic stages of spermatogenesis.|||Nucleus http://togogenome.org/gene/10090:Sell ^@ http://purl.uniprot.org/uniprot/B1B506|||http://purl.uniprot.org/uniprot/P18337|||http://purl.uniprot.org/uniprot/Q3TCF3|||http://purl.uniprot.org/uniprot/Q3UV83 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the selectin/LECAM family.|||Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes (PubMed:1693096). Promotes initial tethering and rolling of leukocytes in endothelia (By similarity).|||Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia.|||Cell membrane|||Interaction with SELPLG/PSGL1 and PODXL2 is required for promoting recruitment and rolling of leukocytes. This interaction is dependent on the sialyl Lewis X glycan modification of SELPLG and PODXL2, and tyrosine sulfation modifications of SELPLG. Sulfation on 'Tyr-51' of SELPLG is important for L-selectin binding.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||N-glycosylated.|||Predominantly expressed in lymphoid tissue. http://togogenome.org/gene/10090:Insm2 ^@ http://purl.uniprot.org/uniprot/Q9JMC2 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in 6.5 to 18.5 dpc embryos and transiently up-regulated from 11.5 to 13.5 dpc. In the developing brain, up-regulated 2 weeks postnatally, with gradual decrease thereafter. Still detectable at 52 weeks.|||Expressed in spleen, stomach, liver, kidney and testis. In the pancreas, expressed in islet cells, including insulin-producing beta-cells, but not in acinar cells (at protein level). In the brain, expressed in the neuronal cells of the cerebral cortex, the Purkinje cells of the cerebellum and the hippocampal region including CA1 and CA3 (at protein level).|||May function as a growth suppressor or tumor suppressor in liver cells and in certain neurons.|||Nucleus|||Up-regulated by NEUROG3 and NEUROD1. http://togogenome.org/gene/10090:Atp6ap1 ^@ http://purl.uniprot.org/uniprot/Q3TWN7|||http://purl.uniprot.org/uniprot/Q3UWN7|||http://purl.uniprot.org/uniprot/Q9R1Q9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump. Interacts (via N-terminus) with ATP6AP2 (via N-terminus). Interacts with RNASEK (By similarity). Interacts with TMEM106B (via C-terminus) (By similarity).|||Accessory subunit of the proton-transporting vacuolar (V)-ATPase protein pump, which is required for luminal acidification of secretory vesicles (PubMed:18713856). Guides the V-type ATPase into specialized subcellular compartments, such as neuroendocrine regulated secretory vesicles or the ruffled border of the osteoclast, thereby regulating its activity. Involved in membrane trafficking and Ca(2+)-dependent membrane fusion. May play a role in the assembly of the V-type ATPase complex. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (By similarity). In islets of Langerhans cells, may regulate the acidification of dense-core secretory granules (PubMed:18713856).|||Belongs to the vacuolar ATPase subunit S1 family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Expressed in brain cortex (at protein level) (PubMed:27231034). Highly expressed in islets of Langerhans (PubMed:18713856). Expressed in pancreatic acini, pituitary gland, adrenal gland, lung, brain and bone marrow (PubMed:18713856).|||N-glycosylated.|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Snapin ^@ http://purl.uniprot.org/uniprot/Q9Z266 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNAPIN family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling. May modulate a step between vesicle priming, fusion and calcium-dependent neurotransmitter release through its ability to potentiate the interaction of synaptotagmin with the SNAREs and the plasma-membrane-associated protein SNAP25. Its phosphorylation state influences exocytotic protein interactions and may regulate synaptic vesicle exocytosis. May also have a role in the mechanisms of SNARE-mediated membrane fusion in non-neuronal cells (PubMed:16760431, PubMed:19546860, PubMed:21998198). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor (By similarity).|||Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos (PubMed:21998198). Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN (By similarity). Associates with the SNARE complex. Interacts with CSNK1D, SNAP23 and STX4A but not with STX1A, VAMP2 and SYT1 (PubMed:12877659, PubMed:17101137). Interacts with SNAP25; the interaction with SNAP25 is increased by its phosphorylation (PubMed:10195194, PubMed:11283605). Interacts with CNTRL, NANOS1, PUM2 and RGS7. Interacts with TOR1A; the interaction is direct and associates SNAPIN with the CSN complex (By similarity).|||Golgi apparatus membrane|||Lysosome membrane|||Membrane|||Phosphorylated by PKD, phosphorylation controls SNAPIN protein stability (By similarity). Phosphorylated by CSNK1D/CK1.|||Strongly expressed in heart, brain, testis, kidney and liver; low expression in spleen, lung and skeletal muscle. In the testis, expressed in the seminiferous tubules.|||cytosol|||perinuclear region|||synaptic vesicle membrane http://togogenome.org/gene/10090:Mrps14 ^@ http://purl.uniprot.org/uniprot/D3Z2K2|||http://purl.uniprot.org/uniprot/Q9CR88 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS14 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins (By similarity). Interacts with LIAT1.|||Mitochondrion http://togogenome.org/gene/10090:Scgb1b12 ^@ http://purl.uniprot.org/uniprot/A0A087WP21 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Rhox7a ^@ http://purl.uniprot.org/uniprot/A2A4F1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Gm21076 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Usp26 ^@ http://purl.uniprot.org/uniprot/Q99MX1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Deubiquitinase regulating several biological processes through the deubiquitination of components of these processes (PubMed:28839133). Involved in somatic cell reprogramming through the 'Lys-48'-linked deubiquitination and stabilization of CBX4 and CBX6, two components of the polycomb-repressive complex 1 (PRC1) (By similarity). Also deubiquitinates and probably stabilizes the androgen receptor (AR), regulating the androgen receptor signaling pathway (By similarity). May play a role in spermatogenesis (By similarity).|||Interacts with RING1.|||Nucleus|||flagellum axoneme http://togogenome.org/gene/10090:Timm10b ^@ http://purl.uniprot.org/uniprot/Q9WV96 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small Tim family.|||Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translocase that uses the membrane potential as the external driving force. In the TIM22 complex, it may act as a docking point for the soluble 70 kDa complex that guides the target proteins in transit through the aqueous mitochondrial intermembrane space.|||Component of the TIM22 complex, which core is composed of TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and TIMM29.|||Mitochondrion inner membrane|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM10B from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane. http://togogenome.org/gene/10090:Cd276 ^@ http://purl.uniprot.org/uniprot/Q8VE98 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Gene transfer of B7-H3 leads to complete regression of 50 per cent tumors, or significantly slows tumor growth.|||Highly expressed in developing bones during embryogenesis and expression increases as osteoblast precursor cells differentiate into mature osteoblasts.|||In primates, B7-H3 locus underwent genomic duplication leading to tandemly repeated immunoglobulin-like V and C domains (VC domains). The dominantly expressed human B7-H3 isoform contains tandemly duplicated VC domains. In contrast, mouse B7-H3 transcript contains only one single VC domain form due to an exon structure corresponding to V domain-(pseudoexon C)-(pseudoexon V)-C domain. This duplication appearing in primates is suggested to be very recent supporting a model of multiple independent emergence of tandem VC repeats within human and monkey species.|||Interacts with TREML2 and this interaction enhances T-cell activation.|||Membrane|||Mice display a lower bone mineral density in cortical bones with femurs more susceptible to bone fracture, but do not exhibit any important skeletal abnormalities. Calvarial cells reveal normal number of osteoblast precursor cells with adequate proliferative capacity, but have impaired osteogenic differentiation. Furthermore, following cardiac transplantation, they display permanent survival under rapamycin regimen and cardiac transplants also show markedly decreased production of key cytokine and chemokine. The incidence of chronic transplant rejection is also inhibited. Mice also develop more severe airway inflammation and experimental autoimmune encephalomyelitis earlier than wild-type littermates as well as accumulate higher concentrations of autoantibodies to DNA.|||Modulates T-cell-mediated immune responses and the development of acute and chronic transplant rejection. Plays a positive regulatory role in bone formation and has a dual role in the bone-immune interface. Induces antitumor immunity as it activates both acquired and innate immunity leading to natural killer cell and CD8 T-cell dependent killing of tumor cells.|||Ubiquitous.|||Up-regulated in cells mediating rejection of mouse transplant. http://togogenome.org/gene/10090:Asb8 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1W1|||http://purl.uniprot.org/uniprot/Q8CDF0|||http://purl.uniprot.org/uniprot/Q91ZT9|||http://purl.uniprot.org/uniprot/Q9D4Y2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Cytoplasm|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Vps35l ^@ http://purl.uniprot.org/uniprot/I1E4X5|||http://purl.uniprot.org/uniprot/Q8BWQ6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. In the endosomes, drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association with the CCC complex and cooperation with the WASH complex on early endosomes. Seems not to be required for CCC complex stability.|||Belongs to the VPS35L family.|||Component of the heterotrimeric retriever complex formed by VPS26C, VPS29 and VPS35L. Interacts with VPS29. Interacts with COMMD1, CCDC93 and CCDC22; associates with the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22 and CCDC93. Interacts with WASHC1, WASHC2A and WASHC2C. Interacts with SNX17 and SNX31.|||Endosome|||Homozygous VPS35L knockout is embryonic lethal at an early stage of embryo development, between 7.5 and 10.5 dpc.|||Membrane http://togogenome.org/gene/10090:Larp4 ^@ http://purl.uniprot.org/uniprot/Q8BWW4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts (via N-terminal region) with PABPC1. Interacts with RACK1.|||RNA binding protein that binds to the poly-A tract of mRNA molecules. Associates with the 40S ribosomal subunit and with polysomes. Plays a role in the regulation of mRNA translation. Plays a role in the regulation of cell morphology and cytoskeletal organization.|||Stress granule|||cytosol http://togogenome.org/gene/10090:Aurka ^@ http://purl.uniprot.org/uniprot/P97477|||http://purl.uniprot.org/uniprot/Q3TEY6 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation at Thr-279; this brings about a change in the conformation of the activation segment (By similarity). Phosphorylation at Thr-279 varies during the cell cycle and is highest during M phase (By similarity). Autophosphorylated at Thr-279 upon TPX2 binding (By similarity). Thr-279 can be phosphorylated by several kinases, including PAK and PKA (By similarity). Protein phosphatase type 1 (PP1) binds AURKA and inhibits its activity by dephosphorylating Thr-279 during mitosis (By similarity). Phosphorylation at Ser-333 decreases the kinase activity (By similarity). PPP2CA controls degradation by dephosphorylating Ser-52 at the end of mitosis (By similarity).|||Activation of CDK1, appears to be an upstream event of AURKA activation (By similarity). Phosphatase inhibitor-2 (PPP1R2) and TPX2 act also as activators (By similarity). Inactivated by the G2 checkpoint (By similarity). Inhibited by GADD45A and p53/TP53, and through dephosphorylation by protein phosphatase type 1 (PP1) (By similarity). MLN8054 is also a potent and selective inhibitor (By similarity). Activated during the early phase of cilia disassembly in the presence of CIMAP3 (By similarity). Inhibited by the small molecule inhibitor VX-680 (By similarity).|||Basolateral cell membrane|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.|||Centrosome amplification can occur when the cycles are uncoupled, and this amplification is associated with cancer and with an increase in the levels of chromosomal instability.|||Death at the blastocyst stage due to mitotic defects and failure of cell proliferation.|||Detected in embryonic neurons in dorsal root ganglia and brain cortex (at protein level). Highly expressed in testis, in about one third of the seminiferous tubules. Expression is restricted to specific spermatocytes nearing completion of prophase, with levels falling off on transition to elongated spermatids. Highly expressed in the ovary, expression in the oocyte starts around the transition to large growing follicle. Abundant expression is seen in the proliferating granulosa and thecal cells of the growing follicle, and in the young corpus luteum. Very weakly expressed in spleen and intestine.|||Expressed during all phases of oocyte maturation; localized at the meiotic spindle and spindle poles during meiosis (PubMed:27753540). At 7.5-9.5 dpc expressed evenly all over the embryo. At later stages, expression is mainly restricted to proliferating zones. The highest levels of expression at mid-embryonic development (13.5 dpc) were observed in the liver, lung, kidney and back (trapezius) muscle and all regions in active proliferation.|||May be less abundant or less stable.|||Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (By similarity). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:9245792, PubMed:19075002). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (By similarity). Required for initial activation of CDK1 at centrosomes (By similarity). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (By similarity). Regulates KIF2A tubulin depolymerase activity (By similarity). Required for normal axon formation (By similarity). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Important for microtubule formation and/or stabilization (By similarity). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (By similarity). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (By similarity). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (By similarity).|||Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (By similarity). Identified in a complex with AUNIP and NIN (By similarity). Interacts with CPEB1, JTB, TACC1, TPX2, PPP2CA, as well as with the protein phosphatase type 1 (PP1) isoforms PPP1CA, PPP1CB and PPP1CC (By similarity). Interacts also with its substrates ARHGEF2, BORA, KIF2A, PARD3, and p53/TP53 (By similarity). Interaction with BORA promotes phosphorylation of PLK1 (By similarity). Interacts with GADD45A, competing with its oligomerization (By similarity). Interacts with FBXL7 and CIMAP3 (PubMed:20643351, PubMed:22306998). Interacts (via C-terminus) with AUNIP (via C-terminus) (By similarity). Interacts with SIRT2 (By similarity). Interacts with FRY; this interaction facilitates AURKA-mediated PLK1 phosphorylation (PubMed:22753416). Interacts with MYCN; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (By similarity). Interacts with HNRNPU (By similarity). Interacts with AAAS (By similarity). Interacts with KLHL18 and CUL3 (By similarity). Interacts with FOXP1 (By similarity). Interacts with HDAC6; AURKA-mediated phosphorylation of HDAC6 promotes deacetylation of alpha-tubulin (By similarity).|||Ubiquitinated by the anaphase-promoting complex (APC), leading to its degradation by the proteasome (By similarity). Ubiquitinated by CHFR, leading to its degradation by the proteasome (PubMed:15793587). Ubiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL7) during mitosis, leading to its degradation by the proteasome (PubMed:22306998).|||centriole|||centrosome|||cilium|||cilium basal body|||expression is cell cycle regulated and peaks at phase G2/M.|||neuron projection|||spindle pole http://togogenome.org/gene/10090:Sbk2 ^@ http://purl.uniprot.org/uniprot/P0C5K1 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily. http://togogenome.org/gene/10090:Dhx15 ^@ http://purl.uniprot.org/uniprot/O35286|||http://purl.uniprot.org/uniprot/Q3UDX4|||http://purl.uniprot.org/uniprot/Q3UKJ6|||http://purl.uniprot.org/uniprot/Q497W9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATPase activity is enhanced upon binding to G-patch domain-containing proteins. G-patch domain-containing proteins act like a brace that tethers mobile sections of DHX15 together, stabilizing a functional conformation with high RNA affinity, thereby promoting the ATPase activity.|||Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily.|||Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (By similarity). Identified in the Intron Large spliceosome complex (IL, also named intron lariat spliceosome), a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors; the association may be transient (By similarity). The IL complex exists in two distinct conformations, one with the DHX15 (ILS2) and one without (ILS1) (By similarity). Interacts with TFIP11 (via G-patch domain); indicative for a recruitment to the IL complex (By similarity). Interacts with SSB/La (By similarity). Interacts with GPATCH2 (via G-patch domain); promoting the RNA helicase activity (By similarity). Interacts with NKRF (via G-patch domain); promoting the RNA helicase activity (By similarity). Interacts with NLRP6 (PubMed:26494172).|||Conditional deletion in intestinal epithelial cells leads to impaired antiviral innate immunity, leading to lethality following infection by an RNA virus (PubMed:34161762). Conditional deletion in intestinal epithelial cells leads to impaired antibacterial immunity, characterized by susceptibility to infection by enteric bacteria C.rodentium (PubMed:33483420). Conditional deletion in Paneth cells leads to reduced expression of alpha-defensins and severe DSS (dextran sodium sulfate)-induced colitis (PubMed:33483420).|||Nucleus|||RNA helicase involved in mRNA processing and antiviral innate immunity (PubMed:26494172, PubMed:34161762). Pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA (By similarity). In cooperation with TFIP11 seem to be involved in the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns (By similarity). Plays a key role in antiviral innate immunity by promoting both MAVS-dependent signaling and NLRP6 inflammasome (PubMed:26494172). Acts as an RNA virus sensor: recognizes and binds viral double stranded RNA (dsRNA) and activates the MAVS-dependent signaling to produce interferon-beta and interferon lambda-3 (IFNL3) (By similarity). Involved in intestinal antiviral innate immunity together with NLRP6: recognizes and binds viral dsRNA and promotes activation of the NLRP6 inflammasome in intestinal epithelial cells to restrict infection by enteric viruses (PubMed:26494172, PubMed:34678144, PubMed:34161762). The NLRP6 inflammasome acts by promoting maturation and secretion of IL18 in the extracellular milieu (PubMed:34161762). Also involved in antibacterial innate immunity by promoting Wnt-induced antimicrobial protein expression in Paneth cells (PubMed:33483420).|||Ubiquitous.|||nucleolus http://togogenome.org/gene/10090:Bnip1 ^@ http://purl.uniprot.org/uniprot/Q6QD59 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of a SNARE complex may be involved in endoplasmic reticulum membranes fusion and be required for the maintenance of endoplasmic reticulum organization. Also plays a role in apoptosis. It is for instance required for endoplasmic reticulum stress-induced apoptosis. As a substrate of RNF185 interacting with SQSTM1, might also be involved in mitochondrial autophagy.|||Belongs to the SEC20 family.|||Component of a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L and SEC22B. Interacts directly with STX18, RINT1/TIP20L and NAPA. Interacts with ZW10 through RINT1. Interacts with BCL2. Interacts with RNF186. Interacts with RNF185. Interacts with SQSTM1; increased by 'Lys-63'-linked polyubiquitination of BNIP1.|||Endoplasmic reticulum membrane|||Mitochondrion membrane|||Polyubiquitinated. 'Lys-63'-linked polyubiquitination by RNF185 increases the interaction with the autophagy receptor SQSTM1. Undergoes 'Lys-29'- and 'Lys-63'-linked polyubiquitination by RNF186 that may regulate BNIP1 localization to the mitochondrion. http://togogenome.org/gene/10090:Chpt1 ^@ http://purl.uniprot.org/uniprot/D3YU39|||http://purl.uniprot.org/uniprot/Q8C025 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CDP-alcohol phosphatidyltransferase class-I family.|||Catalyzes the final step of de novo phosphatidylcholine (PC) synthesis, i.e. the transfer of choline phosphate from CDP-choline to the free hydroxyl of a diacylglycerol (DAG), producing a PC. It thereby plays a central role in the formation and maintenance of vesicular membranes.|||Expressed in brain, heart, lung, liver, spleen, intestine and muscle. Down-regulated in kidney of type 2 diabetic KK/Ta mice.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Abhd16a ^@ http://purl.uniprot.org/uniprot/Q9Z1Q2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. ABHD16 family.|||Membrane|||Mice were born at a much lower frequency than expected and are smaller than wild-type mice throughout development and life (PubMed:25580854). Despite their smaller size, mice appear normal (PubMed:25580854). Metabolomic characterization of brain tissue show decreased lysophosphatidylserines (PubMed:25580854).|||Phosphatidylserine (PS) lipase that mediates the hydrolysis of phosphatidylserine to generate lysophosphatidylserine (LPS) (PubMed:25580854). LPS constitutes a class of signaling lipids that regulates immunological and neurological processes (PubMed:25580854). Has no activity towards diacylglycerol, triacylglycerol or lysophosphatidylserine lipase (By similarity). Also has monoacylglycerol lipase activity, with preference for 1-(9Z,12Z-octadecadienoyl)-glycerol (1-LG) and 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G) (PubMed:25290914).|||Specifically inhibited by alpha-alkylidene-beta-lactone KC01 ((Z)-6-(2-Oxo-4-tridecyloxetan-3-ylidene)hexanamide). http://togogenome.org/gene/10090:Hspa14 ^@ http://purl.uniprot.org/uniprot/Q99M31 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 70 family.|||Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2.|||Component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, binds to the nascent polypeptide chain, while DNAJC2 stimulates its ATPase activity (By similarity).|||cytosol http://togogenome.org/gene/10090:Ttc9 ^@ http://purl.uniprot.org/uniprot/Q3V038 ^@ Similarity ^@ Belongs to the TTC9 family. http://togogenome.org/gene/10090:S100a9 ^@ http://purl.uniprot.org/uniprot/P31725 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the S-100 family.|||Cell membrane|||Cytoplasm|||Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9) (PubMed:34562450). S100A9 interacts with ATP2A2 (PubMed:18403730). S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions (PubMed:17767165, PubMed:19402754, PubMed:18403730). S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with amyloid-beta protein 40. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox) (By similarity).|||Methylation at His-107 by METTL9 reduces zinc-binding without affecting heterodimerization with S100A8.|||No visible phenotype. Alters response of phagocytes to stimulation with bacterial lipopolysaccharide (LPS).|||Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization.|||S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response (PubMed:15331440, PubMed:17767165, PubMed:18403730, PubMed:19402754, PubMed:22804476, PubMed:34562450). It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism (By similarity). Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions (By similarity). The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase (PubMed:15331440). Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX (By similarity). The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities (PubMed:21382888). Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration (By similarity). Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER) (PubMed:17767165, PubMed:18403730, PubMed:19402754). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade (PubMed:17767165, PubMed:18403730, PubMed:19402754, PubMed:22804476). Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth (By similarity). Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3 (By similarity). Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK (By similarity). Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants (By similarity). The iNOS-S100A8/A9 transnitrosylase complex is proposed to direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as GAPDH, NXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif (By similarity).|||Secreted|||cytoskeleton http://togogenome.org/gene/10090:Slx4ip ^@ http://purl.uniprot.org/uniprot/Q9D7Y9 ^@ Similarity|||Subunit ^@ Belongs to the SLX4IP family.|||Interacts with SLX4/BTBD12; subunit of different structure-specific endonucleases. http://togogenome.org/gene/10090:Ifi27l2b ^@ http://purl.uniprot.org/uniprot/Q8VC49 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IFI6/IFI27 family.|||Functions in the intrinsic apoptotic signaling pathway and may have an interferon-induced antiviral activity.|||Homooligomer (PubMed:21151029). Interacts with BAK1 (PubMed:21151029). Interacts with BAX (PubMed:21151029). Interacts with adenine nucleotide translocase (PubMed:21151029).|||Mitochondrion inner membrane|||Up-regulated by type-I interferon (PubMed:21151029). Up-regulated by poly(I:C) (PubMed:21151029). http://togogenome.org/gene/10090:Cdo1 ^@ http://purl.uniprot.org/uniprot/P60334 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the cysteine dioxygenase family.|||Binds 1 Fe(2+) cation per subunit. Ni(2+) and Zn(2+) can be used to a lesser extent.|||Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen.|||Highest expression in liver. Also expressed in kidney, lung, brain and small intestine.|||Monomer.|||The thioether cross-link between Cys-93 and Tyr-157 plays a structural role through stabilizing the Fe(2+) ion, and prevents the production of highly damaging free hydroxyl radicals by holding the oxygen radical via hydroxyl hydrogen. http://togogenome.org/gene/10090:Or2ag1 ^@ http://purl.uniprot.org/uniprot/Q9EPF7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Clxn ^@ http://purl.uniprot.org/uniprot/Q9D3N2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Seems to regulate the assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity). Regulates ciliary and flagellar motility and is required for cilia-driven determination of body laterality (PubMed:31240264).|||Component of the outer dynein arm-docking complex along with ODAD1, ODAD2, ODAD3 and ODAD4.|||Mice display typical phenotypes of primary ciliary dyskinesia, including hydrocephalus, situs inversus, and abnormal motility of trachea cilia and sperm flagella (PubMed:31240264). Strikingly, both males and females are viable and fertile (PubMed:31240264). The 9 + 2 axonemal structures of epithelial multicilia and sperm flagella are normal, but the formation of 9 + 0 nodal cilia is significantly disrupted (PubMed:31240264).|||cilium axoneme http://togogenome.org/gene/10090:Tk1 ^@ http://purl.uniprot.org/uniprot/P04184 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thymidine kinase family.|||Cell-cycle-regulated enzyme of importance in nucleotide metabolism. Catalyzes the first enzymatic step in the salvage pathway converting thymidine into thymidine monophosphate. Transcriptional regulation limits expression to the S phase of the cell cycle and transient expression coincides with the oscillation in the intracellular dTTP concentration.|||Cytoplasm|||Homotetramer. Tetramerization from dimerization is induced by ATP and increases catalytic efficiency due to a high affinity for thymidine. Tetramerization is inhibited by phosphorylation at Ser-13. Interacts (via the KEN box) with FZR1.|||KEN box sequence located in the C-terminal region is required for its mitotic degradation by the APC/C-FZR1 ubiquitin ligase and interaction capability with FZR1.|||Phosphorylated on Ser-13 in mitosis. Phosphorylation of Ser-13 by CDK1 during mitosis reduces homotetramerization and catalytic efficiency when DNA replication is complete and intracellular TK1 is still present at a high level.|||Polyubiquitinated. Postmitosis, ubiquitination leads to proteasomal degradation. The KEN box sequence located at the C-terminal region targets for degradation by the anaphase promoting complex (APC/C) activated and rate-limited by FZR1.|||Two forms have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells. http://togogenome.org/gene/10090:Jarid2 ^@ http://purl.uniprot.org/uniprot/Q62315 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Jumonji' means 'cruciform' in Japanese.|||Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:20064376, PubMed:20064375). Found in a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (By similarity). Facilitates nucleosome binding of the PRC2 complex (By similarity). Interacts with SUZ12 (via C2H2-type zinc finger domain); the interaction is direct; competes with EPOP for SUZ12 binding (By similarity). Interacts with histone methyltransferases EHMT1/GLP1 and EHMT2/G9a (By similarity). Interacts with GATA4 (via the N-terminal region) (PubMed:15542826). Interacts with NKX2-5 (via the C-terminal region) (PubMed:15542826). Interacts with RB1 (PubMed:15870077). Interacts with ZNF496 (PubMed:17521633). Interacts with ESRRB (PubMed:26523946).|||Belongs to the JARID2 family.|||Despite the presence of a JmjC domain, lacks the conserved residues that bind the iron cofactor, explaining the absence of histone methyltransferase activity.|||Embryos die before 15.5 dpc and show severe cardiac morphological defects and altered heart-specific gene expression. Some, but not all, of the homozygotes develop an abnormal groove in a region just anterior to the midbrain-hindbrain boundary on the neural plate at 8-8.5 dpc and show a defect in neural tube closure in the midbrain region. Variable phenotypes are observed depending on the genetic backgrounds: mutant mice with a C57BL/6J X 129S1/Sv genetic background die upon birth and show cardiac defects such as ventricular septal defects, double-outlet right ventricle, and thin ventricular wall at later embryonic stages. In addition to the thin ventricular wall, mutant embryos with a pure BALB/c background show deficient cell growth in the liver, thymus, and spleen. In contrast, mutant mice with a C3H/He genetic background die at 11.5 dpc, which exhibit hyperplasia and increased cyclin-D1 (CCND1) expression in the trabecular layer of the ventricle at 10.5 dpc.|||Nucleus|||Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis (PubMed:10807864, PubMed:12852854, PubMed:12890668, PubMed:15542826, PubMed:15870077, PubMed:19010785, PubMed:20064375, PubMed:20064376, PubMed:20075857). Acts as an accessory subunit for the core PRC2 (Polycomb repressive complex 2) complex, which mediates histone H3K27 (H3K27me3) trimethylation on chromatin (PubMed:20064376, PubMed:20064375). Binds DNA and mediates the recruitment of the PRC2 complex to target genes in embryonic stem cells, thereby playing a key role in stem cell differentiation and normal embryonic development (PubMed:20064375, PubMed:20075857). In cardiac cells, it is required to repress expression of cyclin-D1 (CCND1) by activating methylation of 'Lys-9' of histone H3 (H3K9me) by the GLP1/EHMT1 and G9a/EHMT2 histone methyltransferases (PubMed:12852854, PubMed:12890668, PubMed:19010785). Also acts as a transcriptional repressor of ANF via its interaction with GATA4 and NKX2-5 (PubMed:15542826). Participates in the negative regulation of cell proliferation signaling (PubMed:10913339). Does not have histone demethylase activity (PubMed:20064376).|||The ARID domain is required to target the PRC2 complex to its target genes.|||The GSGFP motif is required for the interaction with SUZ12.|||Widely expressed in embryos. In adults, expressed at high levels in heart, skeletal muscle, brain and thymus. http://togogenome.org/gene/10090:Nlgn2 ^@ http://purl.uniprot.org/uniprot/Q69ZK9|||http://purl.uniprot.org/uniprot/Q6PHN2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Brain and arteries. Detected in the retina outer plexiform layer (at protein level). Widely expressed. Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Cell membrane|||Interacts with neurexins NRXN1, NRXN2 and NRXN3 (By similarity). Interaction with neurexins is mediated by heparan sulfate glycan modification on neurexin (PubMed:30100184). Interacts (via its C-terminus) with DLG4/PSD-95 (via PDZ domain 3). Interacts with PATJ (By similarity). Interacts with MDGA2 (By similarity). Interacts with GPHN (PubMed:19755106). Interacts with MDGA1 (PubMed:23358245). Found in a complex with MAGI2 and IGSF9B, where it interacts with MAGI2 (via WW 1, WW 2 and PDZ 2 domains) (PubMed:23751499). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4; leading to mutual regulation of the protein level and synaptic clustering (PubMed:29742426, PubMed:28279354). Interacts with GABRA1 (By similarity).|||Membrane|||No obvious phenotype, but mice present subtle behavorial changes. Signaling from inhibitory synapses is impaired. In addition, mice have reduced brain volume. Mice lacking both NLGN1 and NLGN2, or NLGN2 and NLGN3, are viable, but have impaired breathing, drastically reduced reproduction rates and striking deficits in raising their offspring. Mice lacking NLGN1, NLGN2 and NLGN3 are born at the expected Mendelian rate, but die shortly after birth due to respiratory failure. They do not show a significant change in the number of synapses, but synapse function is strongly impaired.|||Postsynaptic cell membrane|||Presynaptic cell membrane|||Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion (By similarity). Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Promotes clustering of postsynaptic LHFPL4 (PubMed:29742426). Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. http://togogenome.org/gene/10090:Chordc1 ^@ http://purl.uniprot.org/uniprot/Q9D1P4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subunit|||Tissue Specificity ^@ By Heat shock in a HSF1-dependent manner.|||Interacts with HSP90AA1, HSP90AB1 and PPP5C. Interacts with ROCK1 and ROCK2 (By similarity).|||Regulates centrosome duplication, probably by inhibiting the kinase activity of ROCK2 (PubMed:20230755). Proposed to act as co-chaperone for HSP90 (PubMed:16083881). May play a role in the regulation of NOD1 via a HSP90 chaperone complex (PubMed:16083881). In vitro, has intrinsic chaperone activity (PubMed:20230755). This function may be achieved by inhibiting association of ROCK2 with NPM1 (PubMed:20230755). Plays a role in ensuring the localization of the tyrosine kinase receptor EGFR to the plasma membrane, and thus ensures the subsequent regulation of EGFR activity and EGF-induced actin cytoskeleton remodeling (By similarity). Involved in stress response (PubMed:20493909). Prevents tumorigenesis (By similarity).|||Results in centrosome amplification and lethality. Cells become polyploid or undergo apoptosis. Embryos are no longer detected after 3.5 dpc.|||Ubiquitously expressed. Highly expressed in spleen, lung and brain (at protein level). Expressed in proliferating myoblasts and its expression remained steady after. Its expression undergoes diurnal and circadian changes in hypothalamus. Highly expressed during the dark-light transition (ZT20.5 (zeitgeber time 20.5) and ZT2.5).|||Weakly expressed at ZT8.5 and highly expressed at ZT14.5 at P6. At P6 highly expressed at ZT14.5 in hippocampus, prefrontal cortex and cerebellum. First detected and widely distributed at P1 and that continued throughout postnatal development. Expression is evident in the cortical plate (CP) at 17 dpc. Lower levels of expression is also evident in intermediate (IZ) and subventricular (SVZ) zones at this age. A more diffuse expression pattern is evident in early postnatal cortex with only slight differences in intensity throughout cortical layers. By P14, a more laminated distribution pattern becomes evident with a punctate distribution apparent in deep cortical layers. http://togogenome.org/gene/10090:Ccr2 ^@ http://purl.uniprot.org/uniprot/P51683|||http://purl.uniprot.org/uniprot/Q543S8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Epressed in mature thymocytes (PubMed:29930553). Detected in monocyte/macrophage cell lines, but not in nonhematopoietic cell lines (PubMed:8631787).|||Following a stab wound brain injury, mice show reduced extracellular matrix deposition at the injured gray matter and reduced astroglial scar in the cerebral cortex (PubMed:29632244). The injury site shows an absence of invading monocytes, significantly increased astrocyte proliferation and a decrease in extracellular matrix synthesizing enzymes (PubMed:29632244). Following traumatic brain injury, mice exhibit markedly reduced early macrophage infiltration, improved locomotor activity, improved spatial learning and memory retention and increased neuronal density in the CA1-CA3 regions of the hippocampus (PubMed:24806994). Mice show impaired thymic emigration with a concomitant accumulation of mature thymocytes in the thymus (PubMed:29930553).|||Interacts with ARRB1 (By similarity). Interacts (via extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B; this interaction may preferentially require specific tyrosine sulfation on CCR2 (By similarity). Interacts with NUP85; the interaction is required for CCR2 clusters formation on the cell membrane and CCR2 signaling (By similarity).|||Key functional receptor for CCL2 but can also bind CCL7 and CCL12 chemokines (PubMed:8631787, PubMed:8662823, PubMed:8996246). Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (By similarity). Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B (By similarity). Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation (PubMed:28507030). Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R (PubMed:29930553). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (PubMed:29993042). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (PubMed:29993042). Mediates the recruitment of macrophages and monocytes to the injury site following brain injury (PubMed:24806994, PubMed:29632244).|||Membrane|||N-glycosylated.|||Sulfation increases the affinity for both monomeric and dimeric CCL2 with stronger binding to the monomeric form (By similarity). Binding of sulfated CCR2 to CCL2 promotes conversion of CCL2 from dimer to monomer (By similarity).|||Up-regulated in the dopamine D1 and D2 receptor-containing neurons of nucleus accumbens shell after spinal nerve ligation. http://togogenome.org/gene/10090:Ptp4a2 ^@ http://purl.uniprot.org/uniprot/O70274 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||Cell membrane|||Cytoplasm|||Early endosome|||Expressed in skeletal muscle, and at lower levels in liver, lung, heart, kidney, brain, testis and spleen.|||Farnesylated. Farnesylation is required for membrane targeting and for interaction with RABGGTB (By similarity).|||In contrast to PTP4A1 and PTP4A3, does not interact with tubulin. Interacts with RABGGTB (By similarity).|||Inhibited by sodium orthovanadate and pentamidine.|||Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB (By similarity). http://togogenome.org/gene/10090:Pgghg ^@ http://purl.uniprot.org/uniprot/Q8BP56 ^@ Function|||Similarity ^@ Belongs to the glycosyl hydrolase 65 family.|||Catalyzes the hydrolysis of glucose from the disaccharide unit linked to hydroxylysine residues of collagen and collagen-like proteins. http://togogenome.org/gene/10090:Dglucy ^@ http://purl.uniprot.org/uniprot/Q8BH86 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Accumulation of D-glutamate in heart. Mice develop normally and do not display any visible phenotype under normal conditions.|||Belongs to the D-glutamate cyclase family.|||D-glutamate cyclase that converts D-glutamate to 5-oxo-D-proline.|||Mitochondrion matrix http://togogenome.org/gene/10090:Mphosph6 ^@ http://purl.uniprot.org/uniprot/Q9D1Q1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the RNA exosome complex, probably mediated by EXOSC10. Interacts with ARHGAP18, EXOSC10 and MTREX.|||Belongs to the MPP6 family.|||Cytoplasm|||Phosphorylated in M (mitotic) phase.|||RNA-binding protein that associates with the RNA exosome complex. Involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA and plays a role in recruiting the RNA exosome complex to pre-rRNA; this function may include C1D.|||nucleolus http://togogenome.org/gene/10090:Ube2c ^@ http://purl.uniprot.org/uniprot/A2A4Z0|||http://purl.uniprot.org/uniprot/Q9D1C1 ^@ Function|||PTM|||Similarity|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by initiating 'Lys-11'-linked polyubiquitin chains on APC/C substrates, leading to the degradation of APC/C substrates by the proteasome and promoting mitotic exit.|||Autoubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Its degradation plays a central role in APC/C regulation, allowing cyclin-A accumulation before S phase entry. APC/C substrates inhibit the autoubiquitination of UBE2C/UBCH10 but not its E2 function, hence APC/C remaining active until its substrates have been destroyed.|||Belongs to the ubiquitin-conjugating enzyme family.|||Component of the APC/C complex, composed of at least 14 distinct subunits that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa. Within this complex, directly interacts with ANAPC2. http://togogenome.org/gene/10090:Ppcs ^@ http://purl.uniprot.org/uniprot/Q8VDG5 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the PPC synthetase family.|||Catalyzes the second step in the biosynthesis of coenzyme A from vitamin B5, where cysteine is conjugated to 4'-phosphopantothenate to form 4-phosphopantothenoylcysteine. Has a preference for ATP over CTP as a cosubstrate.|||Homodimer.|||The mammalian enzyme has a preference for ATP over CTP, in contrast to the E.coli ortholog. http://togogenome.org/gene/10090:Ano10 ^@ http://purl.uniprot.org/uniprot/Q8BH79 ^@ Developmental Stage|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Contaminating sequence.|||Detected in the mantle layer of the neural tube and in the dorsal root ganglia at 14.5 dpc.|||Does not exhibit calcium-activated chloride channel (CaCC) activity. Can inhibit the activity of ANO1 (By similarity).|||Predominant expression seen in epithelial tissues.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Selenot ^@ http://purl.uniprot.org/uniprot/P62342 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SelWTH family. Selenoprotein T subfamily.|||Endoplasmic reticulum membrane|||Knockout embryos die before E8 (PubMed:26866473). Male conditional pancreatic beta-cell knockout mice display impaired glucose tolerance with an increased number of smaller islets compared to wild-type littermates (PubMed:23913443). Brain conditional knockout mice treated with Parkinson disease-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rapidly show tremor and absence of movement to die within 2h after treatment (PubMed:26866473).|||May contain a selenide-sulfide bond between Cys-46 and Sec-49. This bond is speculated to serve as redox-active pair (By similarity).|||Rapidly induced by ADCYAP1/PACAP neuropeptide (PubMed:23913443). In striatum neurons and astrocytes, induced by Parkinson disease-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone (PubMed:26866473).|||Selenoprotein with thioredoxin reductase-like oxidoreductase activity (By similarity). Protects dopaminergic neurons against oxidative stress and cell death (PubMed:26866473). Involved in ADCYAP1/PACAP-induced calcium mobilization and neuroendocrine secretion (By similarity). Plays a role in fibroblast anchorage and redox regulation (PubMed:19935881). In gastric smooth muscle, modulates the contraction processes through the regulation of calcium release and MYLK activation (By similarity). In pancreatic islets, involved in the control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP-induced insulin secretion (PubMed:23913443).|||Ubiquitous. Highly expressed in the endocrine pancreas (PubMed:23913443). Expressed at low levels in the adult brain (PubMed:26866473). http://togogenome.org/gene/10090:Dnm2 ^@ http://purl.uniprot.org/uniprot/P39054|||http://purl.uniprot.org/uniprot/Q3T9X3|||http://purl.uniprot.org/uniprot/Q3TCR7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.|||Cell junction|||Cytoplasm|||Exhibits growth and cytokinesis defects.|||Expressed in most tissues during embryonic development, including the peripheral nervous system although no expression is evident in skeletal muscle or heart.|||Interacts with MYOF (PubMed:17702744). Interacts with CTTN and ACTN1 (By similarity). Interacts with SHANK1, SHANK2 and NOSTRIN. Interacts with SH3BP4 (PubMed:17702744, PubMed:16325581). Interacts with SNX9. Interacts with SNX18. Interacts with SNX33 (via SH3 domain). Interacts with MYO1E (via SH3 domain). Interacts with PSTPIP1. Interacts with CTNND2 (By similarity). May interact with PIK3C3 (PubMed:18425118). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (PubMed:18425118). Interacts with BIN1 (By similarity).|||Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Plays an important role in vesicular trafficking processes, in particular endocytosis. Involved in cytokinesis (PubMed:18923138). Regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (PubMed:18425118).|||Midbody|||Phosphorylation at Ser-764 by CDK1 is greatly increased upon mitotic entry. It regulates cytokinesis downstream of calcineurin, and does not affect clathrin-mediated endocytosis. Dephosphorylated by calcineurin/PP2 (By similarity). Phosphorylated on tyrosine residues after activation of SRC (By similarity).|||Postsynaptic density|||Synapse|||clathrin-coated pit|||cytoskeleton|||phagocytic cup|||phagosome membrane http://togogenome.org/gene/10090:Tnnc2 ^@ http://purl.uniprot.org/uniprot/P20801 ^@ Function|||Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the troponin C family.|||Fast skeletal muscle.|||Skeletal muscle troponin C binds four calcium ions.|||Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments. http://togogenome.org/gene/10090:Slc22a4 ^@ http://purl.uniprot.org/uniprot/Q9Z306 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by intracellular ATP.|||Apical cell membrane|||Basal cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Expressed in kidney (PubMed:11010964, PubMed:15832501). Expressed in small intestines (PubMed:20601551). Expressed in liver in non-parenchymal liver tissue such as sinusoidal vessels (PubMed:11010964, PubMed:20601551). Weakly expressed in lung and brain (PubMed:11010964). Expressed in testis and spleen (PubMed:11010964). Expressed in heart (PubMed:16729965).|||Interacts with PDZK1.|||It is unclear whether it transports carnitine in vivo.|||Knockout mice developed normally and did not display any gross phenotypic abnormalities. Knockout mice show a complete deficiency of ergothioneine in heart, liver, small intestine, kidney and erythrocytes. Impaired intestinal absorption and renal reabsorption of ergothioneine (PubMed:20224991, PubMed:20601551). Lower tolerance to intestinal oxidative stress (PubMed:20224991).|||Mediates the Na(+)-independent and pH-dependent bidirectional transport of exogenous prototype organic cation tetraethylammonium (TEA).|||Mitochondrion membrane|||Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations (PubMed:11010964, PubMed:20601551, PubMed:20224991). Functions as a Na(+)-dependent and pH-dependent high affinity microbial symporter of potent food-derived antioxidant ergothioeine (By similarity). Transports one sodium ion with one ergothioeine molecule (By similarity). Involved in the absorption of ergothioneine from the luminal/apical side of the small intestine and renal tubular cells, and into non-parenchymal liver cells, thereby contributing to maintain steady-state ergothioneine level in the body (PubMed:20601551, PubMed:20224991). Also mediates the bidirectional transport of acetycholine, although the exact transport mechanism has not been fully identified yet (By similarity). Most likely exports anti-inflammatory acetylcholine in non-neuronal tissues, thereby contributing to the non-neuronal cholinergic system (By similarity). Displays a general physiological role linked to better survival by controlling inflammation and oxidative stress, which may be related to ergothioneine and acetycholine transports (PubMed:20224991). May also function as a low-affinity Na(+)-dependent transporter of L-carnitine through the mitochondrial membrane, thereby maintaining intracellular carnitine homeostasis (PubMed:11010964, PubMed:16729965). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (By similarity). http://togogenome.org/gene/10090:H1f4 ^@ http://purl.uniprot.org/uniprot/P43274 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ ADP-ribosylated on Ser-55, Ser-113 and Ser-150 in response to DNA damage.|||Acetylated at Lys-26. Deacetylated at Lys-26 by SIRT1.|||Belongs to the histone H1/H5 family.|||Chromosome|||Citrullination at Arg-54 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.|||H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter.|||Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation.|||Hydroxybutyrylation of histones is induced by starvation.|||Nucleus|||The C-terminal domain is required for high-affinity binding to chromatin.|||Triple-deficient mice (H1-2, H1-3 and H1-4) die by midgestation with a broad range of defects. These embryos have about 50% of the normal ratio of H1 to nucleosomes. This proves at least that a correct stoichiometry of linker histone deposition on chromatin is essential. http://togogenome.org/gene/10090:Hunk ^@ http://purl.uniprot.org/uniprot/O88866 ^@ Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. http://togogenome.org/gene/10090:Scara3 ^@ http://purl.uniprot.org/uniprot/Q8C850 ^@ Function|||Subcellular Location Annotation ^@ Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Seems to protect cells by scavenging oxidative molecules or harmful products of oxidation. http://togogenome.org/gene/10090:Azgp1 ^@ http://purl.uniprot.org/uniprot/Q64726 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Interacts with PIP.|||Secreted|||Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. http://togogenome.org/gene/10090:Mapre1 ^@ http://purl.uniprot.org/uniprot/Q3U4H0|||http://purl.uniprot.org/uniprot/Q61166 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-220 by KAT2B/PCAF promotes dynamic kinetochore-microtubule interactions in early mitosis.|||Belongs to the MAPRE family.|||Composed of two functionally independent domains. The N-terminal domain forms a hydrophobic cleft involved in microtubule binding and the C-terminal is involved in the formation of mutually exclusive complexes with APC and DCTN1.|||Crotonylated by KAT5 during mitosis, promoting astral microtubule plasticity and dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation, thereby ensuring accurate spindle positioning in mitosis. Decrotonylated by HDAC3.|||Expressed within the midpiece of sperm tail (at protein level).|||Homodimer (By similarity). Heterodimer with MAPRE3 (By similarity). Interacts (via C-terminal residues 206-211) with APC (via C-terminal residues 2674-2845); the interaction inhibits association with and bundling of F-actin (PubMed:15311282). Interacts with DCTN1, DIAPH1 and DIAPH2 (PubMed:15311282). Interacts with DCTN2, TERF1 and dynein intermediate chain (By similarity). Interacts with CLASP2, DST, KIF2C and STIM1; probably required for their targeting to the growing microtubule plus ends (By similarity). Interacts with MTUS2; interaction is direct and probably targets MTUS2 to microtubules (By similarity). Interacts with APC2 (By similarity). Interacts with CLASP1 (By similarity). Interacts (via C-terminus) with CLIP1 (By similarity). Interacts with SLAIN2 and SLAIN1 (PubMed:21646404). Interacts with MACF1 (PubMed:18854161). Interacts with KIF18B; this interaction is required for efficient accumulation of KIF18B at microtubule plus ends (By similarity). Interacts with MISP (By similarity). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941). Interacts with KCNAB2 (PubMed:21357749). Interacts with KNSTRN (By similarity). Interacts with NCKAP5L (By similarity). Interacts with AKAP9 (By similarity). Interacts with PDE4DIP isoform 2/MMG8/SMYLE; this interaction is required for its recruitment to the Golgi apparatus. May form a pericentrosomal complex with AKAP9, CDK5RAP2 and PDE4DIP isoform 2/MMG8/SMYLE; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP (By similarity). Contrary to other mammalian species, does not interact with CDK5RAP2, possibly due to the lack of conservation of the MAPRE1-binding motif in mouse CDK5RAP2 (PubMed:19553473). Interacts with AKNA (PubMed:30787442). Interacts with GAS2L1, GAS2L2, and GAS2L3 (PubMed:24706950). Interacts with RARRES1 and AGBL2 (By similarity).|||Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules. Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (By similarity). Functions downstream of Rho GTPases and DIAPH1 in stable microtubule formation (PubMed:15311282). May play a role in cell migration (PubMed:15311282).|||centrosome|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Ctsm ^@ http://purl.uniprot.org/uniprot/A0A0R4J182|||http://purl.uniprot.org/uniprot/Q9JL96 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Expressed in adult but not in embryo.|||Lysosome|||Placenta. http://togogenome.org/gene/10090:Aox4 ^@ http://purl.uniprot.org/uniprot/Q3TYQ9 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:23263164).|||Aldehyde oxidase able to catalyze the oxidation of retinaldehyde into retinoate. Is responsible for the major all-trans-retinaldehyde-metabolizing activity in the Harderian gland, and contributes a significant amount of the same activity in the skin. Is devoid of pyridoxal-oxidizing activity, in contrast to the other aldehyde oxidases. Acts as a negative modulator of the epidermal trophism. May be able to oxidize a wide variety of aldehydes into their corresponding carboxylates and to hydroxylate azaheterocycles.|||Belongs to the xanthine dehydrogenase family.|||Binds 1 FAD per subunit.|||Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Binds 2 [2Fe-2S] clusters per subunit.|||Cytoplasm|||Highly expressed in Harderian glands and sebaceous glands with detectable levels in the epidermis and other keratinized epithelia (at protein level). Detected in testis. The expression is 3 times greater in females than in males.|||Homodimer.|||Mice are viable, fertile and born at the expected Mendelian rate. However, they show a deficiency of retinoic acid synthesis in both the Harderian gland and skin. The Harderian gland's transcriptome of knockout mice demonstrates overall down-regulation of direct retinoid-dependent genes as well as perturbations in pathways controlling lipid homeostasis and cellular secretion, particularly in sexually immature animals. The skin is characterized by thickening of the epidermis in basal conditions and after UVB light exposure.|||Repressed by testosterone in Harderian glands. In skin, induced by UVB light. http://togogenome.org/gene/10090:Dkk4 ^@ http://purl.uniprot.org/uniprot/Q8VEJ3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity).|||Belongs to the dickkopf family.|||Interacts with LRP5 and LRP6.|||Secreted|||The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6. http://togogenome.org/gene/10090:Snx14 ^@ http://purl.uniprot.org/uniprot/Q8BHY8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sorting nexin family.|||Expressed at high levels in the brain, testes, and lung and is present in diverse brain regions. Increases significantly during neuron development and maturation.|||Late endosome membrane|||Lysosome membrane|||Plays a role in maintaining normal neuronal excitability and synaptic transmission. May be involved in several stages of intracellular trafficking (PubMed:24859318). Required for autophagosome clearance, possibly by mediating the fusion of lysosomes with autophagosomes. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes/lysosomes. Does not bind phosphatidylinositol 3-phosphate (PtdIns(3P)) (By similarity).|||The SNX14 locus is maternally imprinted.|||dendrite http://togogenome.org/gene/10090:Cnfn ^@ http://purl.uniprot.org/uniprot/G3UWC9|||http://purl.uniprot.org/uniprot/Q6PCW6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cornifelin family.|||Cytoplasm|||Directly or indirectly cross-linked to CE proteins loricin and involucrin (IVL).|||Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia. http://togogenome.org/gene/10090:Rnf180 ^@ http://purl.uniprot.org/uniprot/Q3U827 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in the ventricular zone of the lateral ventricle in brain from 13.5 dpc and 17.5 dpc embryos.|||E3 ubiquitin-protein ligase which promotes polyubiquitination and degradation by the proteasome pathway of ZIC2.|||Endoplasmic reticulum membrane|||Interacts with ZIC2.|||Nucleus envelope|||The RING-type zinc finger domain mediates polyubiquitination of the interacting protein.|||brain, kidney, testis and uterus. membrane protein. Nucleus envelope. http://togogenome.org/gene/10090:Gm20777 ^@ http://purl.uniprot.org/uniprot/Q3TTD8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Tmc5 ^@ http://purl.uniprot.org/uniprot/Q32NZ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMC family.|||Membrane|||Probable ion channel.|||Ubiquitously expressed. http://togogenome.org/gene/10090:S100a13 ^@ http://purl.uniprot.org/uniprot/P97352 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the S-100 family.|||Cytoplasm|||Homodimer. Part of a copper-dependent multiprotein complex containing S100A13, FGF1 and SYT1. Interacts with FGF1 and SYT1. Interacts with IL1A (By similarity).|||Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not to vesicles containing phosphatidylcholine.|||Secreted http://togogenome.org/gene/10090:Inhbc ^@ http://purl.uniprot.org/uniprot/P55104|||http://purl.uniprot.org/uniprot/Q3V2A6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Homodimeric or heterodimeric through association with alpha and beta subunits, linked by one or more disulfide bonds. Inhibins are heterodimers of one alpha and one beta subunit. Activins are homo- or heterodimers of beta subunits only (By similarity).|||Homodimeric or heterodimeric through association with alpha and beta subunits, linked by one or more disulfide bonds. Inhibins are heterodimers of one alpha and one beta subunit. Activins are homo- or heterodimers of beta subunits only.|||Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.|||Mainly expressed in the adult liver.|||Secreted http://togogenome.org/gene/10090:Acy3 ^@ http://purl.uniprot.org/uniprot/Q91XE4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the AspA/AstE family. Aspartoacylase subfamily.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Exists as a mixture of homodimers and homotetramer, both catalytically active.|||Expressed predominantly in kidney and to a lesser extent in liver. Weakly expressed in heart, small intestine, brain, lung, testis, and stomach.|||Plays an important role in deacetylating mercapturic acids in kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids. http://togogenome.org/gene/10090:Nolc1 ^@ http://purl.uniprot.org/uniprot/E9Q5C9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOLC1 family.|||Cytoplasm|||Interacts with RNA polymerase I 194 kDa subunit (RPA194) and with casein kinase-II (By similarity). Interacts with DKC1/NAP57, NOP58 and fibrillarin (By similarity).|||Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (By similarity). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with TCOF1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (By similarity). Involved in nucleologenesis, possibly by playing a role in the maintenance of the fundamental structure of the fibrillar center and dense fibrillar component in the nucleolus (PubMed:11424213). It has intrinsic GTPase and ATPase activities (By similarity).|||Pyrophosphorylated by 5-diphosphoinositol pentakisphosphate (5-IP7) (PubMed:15604408). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue (PubMed:15604408, PubMed:17873058).|||Ubiquitinated. Monoubiquitination by the BCR(KBTBD8) complex promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification.|||Undergoes rapid and massive phosphorylation/dephosphorylation cycles on CK2 and PKC sites. NOLC1 is one of the mostly phosphorylated proteins in the cell.|||nucleolus http://togogenome.org/gene/10090:Il7 ^@ http://purl.uniprot.org/uniprot/P10168|||http://purl.uniprot.org/uniprot/Q3UT18|||http://purl.uniprot.org/uniprot/Q544C8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-7/IL-9 family.|||Deletion mice appear healthy at birth and develop normally. Both sexes are fertile. However, they exhibit severe peripheral blood and tissue lymphoid abnormalities showing a strong dependence on IL7 for proper expansion of lymphoid lineages.|||Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintaining lymphoid homeostasis (PubMed:7699333, PubMed:28811625). Mechanistically, exerts its biological effects through a receptor composed of IL7RA subunit and the cytokine receptor common subunit gamma/CSF2RG. Binding to the receptor leads to activation of various kinases including JAK1 or JAK3 depending on the cell type and subsequently propagation of signals through activation of several downstream signaling pathways including the PI3K/Akt/mTOR or the JAK-STAT5.|||Hematopoietic cytokine that plays an essential role in the development, expansion, and survival of naive and memory T-cells and B-cells thereby regulating the number of mature lymphocytes and maintaining lymphoid homeostasis.|||Interacts with IL7R and CSF2RG.|||Secreted|||Three disulfide bonds are present. http://togogenome.org/gene/10090:Dnajc28 ^@ http://purl.uniprot.org/uniprot/Q8VCE1 ^@ Function ^@ May have a role in protein folding or as a chaperone. http://togogenome.org/gene/10090:Upk1b ^@ http://purl.uniprot.org/uniprot/Q9Z2C6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Bladder epithelium.|||Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions (By similarity).|||Heterodimer with uroplakin-3A (UPK3A) or uroplakin-3B (UPK3B).|||Membrane|||N-glycosylated with high-mannose oligosaccharides. http://togogenome.org/gene/10090:Ifnl2 ^@ http://purl.uniprot.org/uniprot/Q4VK74 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the lambda interferon family.|||Cytokine with antiviral, antitumour and immunomodulatory activities. Plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Seems not to be essential for early virus-activated host defense in vaginal infection, but plays an important role in Toll-like receptor (TLR)-induced antiviral defense. Plays a significant role in the antiviral immune defense in the intestinal epithelium. Exerts an immunomodulatory effect by up-regulating MHC class I antigen expression.|||Secreted http://togogenome.org/gene/10090:Nudt7 ^@ http://purl.uniprot.org/uniprot/Q99P30 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. PCD1 subfamily.|||Expressed in liver, brown adipose tissue and heart at 20 times lower levels than isoform 1.|||Expression decreases in response to peroxisome proliferators.|||Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate (PubMed:11415433, PubMed:18799520, PubMed:29378847). Cleaves CoA, CoA esters and oxidized CoA with similar efficiencies (PubMed:11415433). Preferentially hydrolyzes medium-chain acyl-CoAs and bile acid-CoAs (PubMed:18799520). Has no activity toward NDP-sugars, CDP-alcohols, (deoxy)nucleoside 5'-triphosphates, nucleoside 5'-di or monophosphates, diadenosine polyphosphates, NAD, NADH, NADP, NADPH or thymidine-5'-monophospho-p-nitrophenyl ester (PubMed:18799520). May be required to eliminate oxidized CoA from peroxisomes, or regulate CoA and acyl-CoA levels in this organelle in response to metabolic demand (PubMed:18799520). Does not play a role in U8 snoRNA decapping activity (PubMed:21070968). Binds U8 snoRNA (PubMed:21070968). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (PubMed:32432673).|||Highly expressed in liver, brown adipose tissue and heart. Expressed at intermediate level in lung and kidney and at low level in brain.|||Inactive.|||Inhibited by fluoride.|||Monomer.|||Peroxisome http://togogenome.org/gene/10090:Myo15a ^@ http://purl.uniprot.org/uniprot/Q9QZZ4 ^@ Caution|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Defects in Myo15a are the cause of shaker-2 (sh-2), a condition causing deafness, circling behavior, head tossing and hyperactivity. Auditory hair cells of affected animals have very short stereocilia and a long actin-containing protrusion at their basal end.|||In the developing inner ear, expressed in cochlea and vestibular apparatus. Expression appears to be restricted to cochlear neurosensory cells and upper epithelial layer of macula saccula. Also expressed in macula utriculi and cristae ampullaris of the semicircular canals. In adult cochlear hair cells, highest expression in stereocilia and apical body.|||Interacts with the third PDZ domain of WHRN which is necessary for localization of WHRN to stereocilium tips. Interacts with FASLG (By similarity). Interacts with EPS8.|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity). Required for the arrangement of stereocilia in mature hair bundles.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-15 (MYH15).|||cytoskeleton|||stereocilium http://togogenome.org/gene/10090:Rbm48 ^@ http://purl.uniprot.org/uniprot/H9H9R8|||http://purl.uniprot.org/uniprot/Q8K2X2 ^@ Function|||Similarity|||Subunit ^@ As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.|||Belongs to the RBM48 family.|||Component of the minor spliceosome. Within this complex, interacts with ARMC7 and PRPF8/PRP8. http://togogenome.org/gene/10090:Rcsd1 ^@ http://purl.uniprot.org/uniprot/Q3UZA1 ^@ Function|||PTM|||Subunit ^@ Dephosphorylation results in its dissociation from CAPZA2.|||Interacts with CAPZA2 and CAPZB.|||Stress-induced phosphorylation of CAPZIP may regulate the ability of F-actin-capping protein to remodel actin filament assembly. http://togogenome.org/gene/10090:Stk32c ^@ http://purl.uniprot.org/uniprot/Q8QZV4 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Or2m13 ^@ http://purl.uniprot.org/uniprot/Q8VFA2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmprss11f ^@ http://purl.uniprot.org/uniprot/Q8BHM9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Membrane|||Probable serine protease. http://togogenome.org/gene/10090:Retnlg ^@ http://purl.uniprot.org/uniprot/Q8K426 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the resistin/FIZZ family.|||Expressed in colon, lung, spleen, pancreas, ileum and bone marrow (at protein level) (PubMed:15834545). In colon, found throughout the crypt and surface epithelium, including goblet cells (at protein level) (PubMed:15834545). Highest expression is observed in bone marrow, spleen and lung, with lower levels in other tissues (PubMed:12782128, PubMed:14733912, PubMed:15064728, PubMed:15834545). Detected at low levels in granulocytes, but not found in monocytes or lymphocytes (PubMed:14733912). Has very weak expression in white adipose tissue (PubMed:12782128).|||Homodimer. Heterodimer with RETNLB.|||In liver, strongly expressed at 18 dpc and at birth, and then rapidly declines. In pancreas, strongly expressed at birth with decreasing expression after 4 days of age. Also shows strong expression in neonatal gut, lung and heart.|||Probable hormone (Probable). Promotes chemotaxis in myeloid cells (PubMed:15064728).|||Secreted|||Up-regulated in colon and bone marrow in response to a high-fat diet. Also up-regulated in obese mice mutant for the leptin receptor LEPR (db/db genotype). http://togogenome.org/gene/10090:Vrk2 ^@ http://purl.uniprot.org/uniprot/Q8BN21 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in liver, kidney and muscle. Weakly expressed in thymus, bone marrow and spleen.|||Interacts with MAP3K7, MAP2K7, MAP2K1, KSR1, RAN and MAPK8IP1.|||Mitochondrion membrane|||Nucleus envelope|||Serine/threonine kinase that regulates several signal transduction pathways (PubMed:14645249). Modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes (By similarity). Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription (By similarity). Phosphorylates histone H3 (By similarity). Phosphorylates 'Thr-18' of p53/TP53, and thereby increases its stability and activity (By similarity). Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins (By similarity). Down-regulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1 (By similarity). Blocks the phosphorylation of ERK in response to ERBB2 and HRAS (By similarity). May also phosphorylate MAPK8IP1 (By similarity). Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant (By similarity).|||Weakly expressed in embryo compared to VRK1 and VRK3. Expressed from 10.5 dpc to 14 dpc in developing liver and then decreases. It increases again from 17.5 dpc and remains thereafter. Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to 14.5 dpc. Weakly expressed in the yolk-sac. http://togogenome.org/gene/10090:Nxph1 ^@ http://purl.uniprot.org/uniprot/Q61200 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neurexophilin family.|||Brain, only in a scattered subpopulation of neurons that probably represent inhibitory interneurons.|||May be proteolytically processed at the boundary between the N-terminal non-conserved and the central conserved domain in neuron-like cells.|||May be signaling molecules that resemble neuropeptides. Ligand for alpha-neurexins.|||Secreted http://togogenome.org/gene/10090:Wsb1 ^@ http://purl.uniprot.org/uniprot/O54927 ^@ Domain|||Function|||Subunit ^@ Interacts with DIO2. Component of the probable ECS(WSB1) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and WSB1. Component of a probable ECS-like E3 ubiquitin-protein ligase complex which contains CUL5, RBX1, Elongin BC complex and WSB1. Interacts with CUL5, RNF7, ELOB and ELOC. Binds to HIPK2 through WD40 repeats (By similarity).|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes type II iodothyronine deiodinase/DIO2. Confers constitutive instability to HIPK2 through proteasomal degradation (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes. http://togogenome.org/gene/10090:Adat3 ^@ http://purl.uniprot.org/uniprot/Q6PAT0 ^@ Caution|||Similarity ^@ Belongs to the cytidine and deoxycytidylate deaminase family. ADAT3 subfamily.|||Val-225 is present instead of the conserved Glu which is an active site in the cytidine and deoxycytidylate deaminase family of enzymes. It is suggested that this protein may act as a regulatory subunit. http://togogenome.org/gene/10090:Ccdc7a ^@ http://purl.uniprot.org/uniprot/Q9D541 ^@ Function|||Tissue Specificity ^@ Exclusively expressed in the testes. Abundantly expressed in mouse cancer cell line derived from epithelial cells.|||May play a role in tumorigenesis. http://togogenome.org/gene/10090:Rtcb ^@ http://purl.uniprot.org/uniprot/Q99LF4 ^@ Cofactor|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RtcB family.|||Binds 2 manganese ions per subunit.|||Catalytic component of the tRNA-splicing ligase complex.|||Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity, and may function toward other RNAs (By similarity). Essential during post-implantation development of embryos.|||Cytoplasm|||Down-regulated in the epididymis upon castration.|||Ligation probably proceeds through 3 nucleotidyl transfer steps, with 2',3'-cyclic phosphate termini being hydrolyzed to 3'-P termini in a step that precedes 3'-P activation with GMP. In the first nucleotidyl transfer step, RTCB reacts with GTP to form a covalent RTCB-histidine-GMP intermediate with release of PPi; in the second step, the GMP moiety is transferred to the RNA 3'-P; in the third step, the 5'-OH from the opposite RNA strand attacks the activated 3'-P to form a 3',5'-phosphodiester bond and release GMP.|||Nucleus|||Ubiquitously expressed. Highly expressed in the epididymis with predominant enrichment in the initial segment. During sexual maturation, it is expressed in the caput epididymides. http://togogenome.org/gene/10090:Or5h17 ^@ http://purl.uniprot.org/uniprot/E9QKE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or10q3 ^@ http://purl.uniprot.org/uniprot/Q7TQS2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5w11 ^@ http://purl.uniprot.org/uniprot/Q7TR45 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ctsd ^@ http://purl.uniprot.org/uniprot/P18242|||http://purl.uniprot.org/uniprot/Q3UCD9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation.|||Belongs to the peptidase A1 family.|||Consists of a light chain and a heavy chain. Interacts with ADAM30; this leads to activation of CTSD. Interacts with GRN; stabilizes CTSD; increases its proteolytic activity (PubMed:28453791).|||Lysosome|||Melanosome|||N- and O-glycosylated.|||Undergoes proteolytic cleavage and activation by ADAM30.|||extracellular space http://togogenome.org/gene/10090:Npcd ^@ http://purl.uniprot.org/uniprot/F8VQB8|||http://purl.uniprot.org/uniprot/H3BLN6|||http://purl.uniprot.org/uniprot/Q6TLW0|||http://purl.uniprot.org/uniprot/Q6TLW1 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Fastkd3 ^@ http://purl.uniprot.org/uniprot/Q8BSN9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAST kinase family.|||Expression detected in spleen, testis, colon, heart, smooth muscle, kidney, brain, lung, liver, brown and white adipose tissue with highest expression in testis and smooth muscle.|||Mitochondrion|||RAP domain is required for FASTKD3 function in mRNA stability and translation.|||Required for normal mitochondrial respiration. Increases steady-state levels and half-lives of a subset of mature mitochondrial mRNAs MT-ND2, MT-ND3, MT-CYTB, MT-CO2, and MT-ATP8/6. Promotes MT-CO1 mRNA translation and increases mitochondrial complex IV assembly and activity. http://togogenome.org/gene/10090:Exoc6 ^@ http://purl.uniprot.org/uniprot/A0A5F8MP92|||http://purl.uniprot.org/uniprot/Q3U9D6 ^@ Function|||Similarity ^@ Belongs to the SEC15 family.|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. http://togogenome.org/gene/10090:Or5h25 ^@ http://purl.uniprot.org/uniprot/Q7TS43 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccl17 ^@ http://purl.uniprot.org/uniprot/F6R5P4|||http://purl.uniprot.org/uniprot/Q9WUZ6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemokine, which displays chemotactic activity for T lymphocytes, preferentially Th2 cells, but not monocytes or granulocytes. Therefore plays an important role in a wide range of inflammatory and immunological processes (PubMed:10508243, PubMed:10508268). Acts by binding to CCR4 at T-cell surface (By similarity). Mediates GM-CSF/CSF2-driven pain and inflammation (PubMed:27525438). In the brain, required to maintain the typical, highly branched morphology of hippocampal microglia under homeostatic conditions. May be important for the appropriate adaptation of microglial morphology and synaptic plasticity to acute lipopolysaccharide (LPS)-induced neuroinflammation (PubMed:30277599). Plays a role in wound healing, mainly by inducing fibroblast migration into the wound (PubMed:21521373).|||Expressed in primary and secondary lymphoid organs, where it is specifically produced by a subset of dendritic cells. Not expressed in the spleen (PubMed:12615900). Constitutively expressed in thymus, as well as in the lung, skin and intestine (PubMed:10508243, PubMed:10508268, PubMed:12615900). Not expressed in bone marrow-derived macrophages and activated B cells, nor in thymocytes (PubMed:10508243, PubMed:10508268). In the brain, predominantly expressed in a subset of hippocampal CA1 neurons (PubMed:30277599).|||In macrophages, up-regulated by IL4 and by GM-CSF/CSF2 in an IRF4-dependent manner (at protein level) (PubMed:29871928). Up-regulated in response to various Toll-like receptors ligands, including lipopolysaccharide (LPS), CpG-oligodeoxynucleotide (CpG), PAM3Cys, poly(I:C) in dendritic cells (PubMed:12615900, PubMed:30277599). Up-regulated by TNF in dendritic cells (PubMed:12615900). In hippocampal neurons, up-regulated by LPS, possibly via a TNF-dependent pathway, but not by CpG nor by poly(I:C) (PubMed:30277599).|||Knockout mice mount diminished T cell-dependent contact hypersensitivity responses and display a deficiency in rejection of allogeneic organ transplants (PubMed:12615900). In hippocampus, the absolute cell numbers of microglia is significantly reduced compared to wild-type mice. Under homeostatic conditions, microglia possess a smaller cell volume, reduced cell surface area, number of branches and junctions, as well as total tree length compared to those of control mice. This specific morphology of microglia partially resembles that observed in lipopolysaccharide (LPS)-stimulated wild-type animals. Basal synaptic transmission is significantly increased in CA3-CA1 Schaffer collateral synapses in acute brain slices compared to wild-type mice (PubMed:30277599).|||Not detected in the thymus before birth.|||Secreted http://togogenome.org/gene/10090:Sting1 ^@ http://purl.uniprot.org/uniprot/A0A2R3XZC4|||http://purl.uniprot.org/uniprot/Q3TBT3 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by anticancer drug 5,6-dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:23910378, PubMed:26669264). Specifically inhibited by nitrofuran derivatives C-178 and C-176, which covalently bind Cys-91 and prevent palmitoylation and subsequent activation od STING1 (PubMed:29973723).|||Belongs to the STING family.|||Cell membrane|||Defects in innate immunity. Death within 7 days of herpes simplex virus 1 (HSV-1) infection. In addition, mice show a remarkable reduction in cytotoxic T-cell responses after plasmid DNA vaccination. Cells fail to induce type I interferon production in response to dsDNA and infection with herpes simplex virus 1 (HSV-1) and L.monocytogenes that deliver DNA to the host cytosol.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Expressed throughout the B-cell lineage prior to the plasma cell stage but occurs at highest levels in mature B-cells. Highly expressed in cells representing mature stages of B-cells but weakly expressed in pre-B cells, immature B-cells, and memory B-cell stages. Not detected in plasma cells.|||Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264, PubMed:27324217, PubMed:28529930, PubMed:29973723). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23722158, PubMed:23258412, PubMed:23519410, PubMed:23910378). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state (PubMed:25636800, PubMed:27324217, PubMed:29973723). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (PubMed:29056340). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:26300263). The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation (By similarity). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (By similarity). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (PubMed:18559423).|||Golgi apparatus membrane|||Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-150 is required for homodimerization (PubMed:18559423). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (By similarity). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By similarity). Interacts with RIGI, MAVS and SSR2 (By similarity). Interacts with RNF5 and TRIM56 (By similarity). Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta (By similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts with TRIM29; this interaction induces STING1 ubiquitination and subsequent degradation (By similarity). Associates with the MHC-II complex (PubMed:18559423). Interacts with STEEP; the interaction is increased upon cGAMP binding and promotes STING1 translocation to COPII vesicles (By similarity). Interacts with SEC24A, SEC24B and SEC24C; promoting translocation to COPII vesicles (By similarity). Interacts (when ubiquitinated) with SQSTM1; leading to relocalization to autophagosomes (PubMed:29496741). Interacts with SURF4 (By similarity). Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with ZDHHC1; ZDHHC1 constitutively interacts with STING1 and in presence of DNA viruses activates it by promoting its cGAMP-induced oligomerization and the recruitment of downstream signaling components (By similarity). Interacts with ZDHHC11; in presence of DNA viruses promotes the recruitment of IRF3 to STING1 (By similarity). Interacts with TOMM70 (By similarity). Interacts with IFI204 (PubMed:28529930).|||In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (By similarity). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (By similarity).|||Mitochondrion outer membrane|||Palmitoylation takes place in the Golgi apparatus and creates a platform for the recruitment of TBK1.|||Phosphorylation by TBK1 leads to activation and production of IFN-beta (By similarity). Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at Ser-365 in the pLxIS motif (By similarity). The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines (PubMed:27637147). The phosphorylated pLxIS motif facilitates SENP2 recruitment during late phase of viral infection (PubMed:27637147). Phosphorylated on tyrosine residues upon MHC-II aggregation (PubMed:18559423). Dephosphorylation by PPP6C leads to inactivation and decreased production of IFN-beta (By similarity). Phosphorylation at Ser-357 is also required to activate IRF3 (PubMed:25636800).|||Present in spleen and thymus tissue. Also present in dendritic cells (at protein level).|||Sumoylated at Lys-337 by TRIM38 during the early phase of viral infection, promoting its stability by preventing its relocalization to autophagosomes and subsequent degradation (PubMed:27637147). Desumoylated by SENP2 during the late phase of viral infection (PubMed:27637147).|||The N-terminal domain interacts with glycerophospholipids and phospholipids.|||The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines.|||Ubiquitinated (PubMed:29496741). Ubiquitinated via 'Lys-63'-linked ubiquitin chains in response to double-stranded DNA treatment, leading to relocalization to autophagosomes and subsequent degradation; this process is dependent on SQSTM1 (PubMed:29496741). 'Lys-63'-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta (By similarity). 'Lys-48'-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation (By similarity). 'Lys-11'-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it protects STING1 from RNF5-mediated 'Lys-48'-linked polyubiquitination (By similarity). 'Lys-33'-linked and 'Lys-48'-linked deubiquitinated by USP20; leading to its stabilization and promotion of innate antiviral response (By similarity). 'Lys-48'-linked deubiquitinated by USP44; leading to its stabilization and promotion of innate antiviral response (By similarity). Deubiquitinated by USP13; leading to inhibition of innate antiviral response (By similarity).|||Was named MPYS because the protein sequence begins by Met-Pro-Tyr-Ser residues.|||autophagosome membrane|||perinuclear region http://togogenome.org/gene/10090:Lrrc8e ^@ http://purl.uniprot.org/uniprot/Q66JT1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LRRC8 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Heterohexamer. Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8C, LRRC8D and/or LRRC8B) to form a heterohexamer. Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E. In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist.|||Lysosome membrane|||No visible phenotype in normal conditions (PubMed:32277911). Impaired response to herpes simplex virus 1 (HSV-1) infection, caused by decreased ability to transport 2'-3'-cGAMP (PubMed:32277911).|||Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (By similarity). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Mediates efflux of amino acids, such as aspartate, in response to osmotic stress (By similarity). The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:32277911). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (By similarity). Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis (By similarity).|||The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins. http://togogenome.org/gene/10090:Slc4a10 ^@ http://purl.uniprot.org/uniprot/B1AWV9|||http://purl.uniprot.org/uniprot/Q5DTL9|||http://purl.uniprot.org/uniprot/Q8C943|||http://purl.uniprot.org/uniprot/R4H243 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Expressed at high levels in brain and at low levels in the pituitary, testis, kidney and ileum. Also expressed in pancreatic islets.|||Has been shown to act as a sodium/bicarbonate cotransporter in exchange for intracellular chloride (PubMed:10993873, PubMed:20566632). Has also been shown to act as a sodium/biocarbonate cotransporter which is not responsible for net efflux of chloride, with the observed chloride efflux being due to chloride self-exchange (By similarity).|||Homozygotes are born at the expected Mendelian ratio but most pups die around weaning (PubMed:18165320). When fed soft food from the second week of life onward, most pups catch up with the weight of their wild-type littermates and survive (PubMed:18165320). Adults display normal weight and lifespan, are fertile and do not display major behavioral abnormalities (PubMed:18165320). However, brain ventricle size is drastically reduced and mutants show diminished Na(+)-dependent recovery of pH following acid loading of choroid plexus epithelial cells (PubMed:18165320). Mutants also show reduced excitability of CA3 pyramidal neurson and have increased seizure threshold (PubMed:18165320). Increased excitability of CA1 pyramidal neurons and diminished paired pulse facilitation in the hippocampus (PubMed:26136660). No obvious morphological changes in the retina but mutants display decreased visual acuity and contrast sensitivity in behavioral experiments, smaller scotopic and photopic b-wave amplitudes and longer latencies in electroretinograms, and altered temporal response properties of ganglion cells (PubMed:23056253).|||In the brain, detected in cerebral cortex, subcortex, cerebellum, hippocampus and medulla (at protein level) (PubMed:20541593, PubMed:18061361, PubMed:21439947, PubMed:24905082). In the cerebrum, expressed at high levels throughout the cortex, at lower levels in striatum and not detectable in the corpus callosum (at protein level) (PubMed:20541593). In the cerebellum, detected at high levels in the molecular layer but at very low levels in the granular layer (at protein level) (PubMed:20541593). In the central nervous system, detected in neurons in the olfactory bulb, cortex and cerebellum (at protein level) (PubMed:18165320). Within the hippocampus, abundantly expressed in CA3 pyramidal cells (at protein level) (PubMed:18165320). Strongly expressed in the retina with high levels in bipolar and amacrine cells (at protein level) (PubMed:23056253). Expressed in the epithelial cells of the choroid plexus (PubMed:14592810, PubMed:15567717). During embryonic development, expressed in neurons of the central nervous system (PubMed:15567717). Also expressed in the peripheral nervous system and in non-neuronal tissues such as the dura and some epithelia including the acid-secreting epithelium of the stomach and the duodenal epithelium (PubMed:15567717). In the embryonic retina, expression is restricted to the neuronal cell layer and the retinal pigment epithelium (PubMed:15567717).|||In the embryonic central nervous system, detected at 12.5 dpc when expression is observed in all areas of the brain including the cerebellum (PubMed:15567717). In the embryonic cerebral cortex, detected at 14.5 dpc with levels increasing at 18.5 dpc (PubMed:15567717).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lateral cell membrane|||Membrane|||N-glycosylated.|||Perikaryon|||Postsynapse|||Presynapse|||Repressed in the brain by chronic continuous hypoxia (at protein level).|||Sodium/bicarbonate cotransporter which mediates cotransport of sodium and bicarbonate in association with an efflux of intracellular chloride.|||Sodium/bicarbonate cotransporter which plays an important role in regulating intracellular pH (PubMed:20566632). Has been shown to act as a sodium/bicarbonate cotransporter in exchange for intracellular chloride (PubMed:20566632). Has also been shown to act as a sodium/biocarbonate cotransporter which is not responsible for net efflux of chloride, with the observed chloride efflux being due to chloride self-exchange (By similarity). Controls neuronal pH and may contribute to the secretion of cerebrospinal fluid (PubMed:18165320). Reduces the excitability of CA1 pyramidal neurons and modulates short-term synaptic plasticity (PubMed:26136660). Required in retinal cells to maintain normal pH which is necessary for normal vision (PubMed:23056253). In the kidney, likely to mediate bicarbonate reclamation in the apical membrane of the proximal tubules (By similarity).|||The N-terminal cytoplasmic domain is likely to have a high level of intrinsic disorder.|||Zinc-binding negatively regulates its activity.|||axon|||dendrite http://togogenome.org/gene/10090:Abi1 ^@ http://purl.uniprot.org/uniprot/B7ZCU0|||http://purl.uniprot.org/uniprot/B7ZCU3|||http://purl.uniprot.org/uniprot/B7ZCU4|||http://purl.uniprot.org/uniprot/Q3TJ64|||http://purl.uniprot.org/uniprot/Q3TJR5|||http://purl.uniprot.org/uniprot/Q3TPY5|||http://purl.uniprot.org/uniprot/Q8CBW3 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ABI family.|||Cytoplasm|||Detected at 10 dpc and 12 dpc in developing brain, but does not appear more prominent in the neuroepithelium compared to the surrounding tissue.|||Interacts with ENAH, Abelson murine leukemia virus V-ABL, ABL1, STX1A, SNAP25, VAMP2, and through its N-terminus with WASF1. Part of a complex consisting of ABI1, STX1A and SNAP25. Part of a complex consisting of ABI1, EPS8 and SOS1. Interacts with EPS8, SOS1, SOS2, GRB2, SPTA1, and the first SH3 domain of NCK1 (By similarity). Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2. Interacts (via SH3 domain) with SHANK2 and SHANK3, but not SHANK1; the interaction is direct. Interacts with the heterodimer MYC:MAX; the interaction may enhance MYC:MAX transcriptional activity. Interacts with FNBP1L (via the SH3 domain), WASF2, and CDC42, but only in the presence of FNBP1L (By similarity).|||May act in negative regulation of cell growth and transformation by interacting with nonreceptor tyrosine kinases ABL1 and/or ABL2. In vitro, at least isoform 2 and isoform 4 suppress the transforming activity of Abelson murine leukemia virus (v-Abl) after overexpression in fibroblasts. May play a role in regulation EGF-induced Erk pathway activation. Involved in cytoskeletal reorganization and EGFR signaling. Together with EPS8 participates in transduction of signals from Ras to Rac. In vitro, a trimeric complex of ABI1, EPS8 and SOS1 exhibits Rac specific guanine nucleotide exchange factor (GEF) activity and ABI1 seems to act as an adapter in the complex. Regulates ABL1/c-Abl-mediated phosphorylation of ENAH. Recruits WASF1 to lamellipodia and there seems to regulate WASF1 protein level. In brain, seems to regulate the dendritic outgrowth and branching as well as to determine the shape and number of synaptic contacts of developing neurons.|||Nucleus|||Phosphorylated on tyrosine residues after serum stimulation or induction by v-Abl. Seems to be phosphorylated at Tyr-53 by ABL1, required for nuclear but not for synaptic localization (By similarity).|||Postsynaptic density|||The t-SNARE coiled-coil homology domain is necessary and sufficient for interaction with STX1A.|||Widely expressed with highest levels in bone marrow, spleen, brain, testes, and embryonic brain. In adult brain prominently expressed in the neocortex, hippocampus and dentate gyrus.|||cytoskeleton|||filopodium|||growth cone|||lamellipodium http://togogenome.org/gene/10090:Lrfn3 ^@ http://purl.uniprot.org/uniprot/Q8BLY3 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRFN family.|||Can form heteromeric complexes with LRFN1, LRFN2, LRFN4 and LRFN5. Able to form homomeric complexes across cell junctions, between adjacent cells. Does not interact with DLG4.|||Cell adhesion molecule that mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Promotes neurite outgrowth in hippocampal neurons.|||Cell membrane|||Expressed from 4.5 to 18.5 dpc. Initial levels are low until 6.5 dpc and residual from 7.5 to 9.5 dpc. Expression increases from 10.5 to 15.5 dpc before falling again to a level slightly higher than the one seen on 4.5 to 6.5 dpc. At 11.5 dpc, broadly expressed in the telencephalic and diencephalic vesicles. At 17.5 dpc, expressed in cerebral cortex, hippocampus, dorsal thalamus and amygdala.|||Expressed in brain, testis, stomach, small intestine and kidney. Residually expressed in heart, lung, liver, skeletal muscle and uterus. In the brain, weak, but broad expression in the cerebral cortex and diencephalic nuclei. Also detected in other parts of the central nervous system, including the olfactory bulb, pons, cerebellum, and medulla oblongata, as well as in the peripheral nervous system, such as the ganglia of cranial nerves and the dorsal root ganglion during gestation.|||Lacks a cytoplasmic PDZ-binding domain, which has been implicated in function of related Lrfn proteins.|||N-glycosylated.|||Postsynaptic cell membrane|||Presynaptic cell membrane|||Synapse|||axon|||dendrite http://togogenome.org/gene/10090:Kcne1 ^@ http://purl.uniprot.org/uniprot/P23299|||http://purl.uniprot.org/uniprot/Q545H6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr).|||Apical cell membrane|||Belongs to the potassium channel KCNE family.|||Cell membrane|||Interacts with KCNB1. Interacts with KCNC2 (By similarity). Associates with KCNH2/HERG. Interacts with KCNQ1; targets the complex KCNQ1-KCNE1 to the membrane raft (By similarity) (PubMed:8900282).|||Membrane|||Membrane raft|||N-glycosylation at Asn-26 occurs post-translationally, and requires prior cotranslational glycosylation at Asn-5.|||Phosphorylation inhibits the potassium current.|||Restrictively localized in the apical membrane portion of epithelial cells. http://togogenome.org/gene/10090:Mmgt1 ^@ http://purl.uniprot.org/uniprot/Q8K273 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in heart muscle and kidney with lower levels in liver and brain and very little expression in intestine or colon. In kidney, highest levels in distal convoluted tubule.|||Belongs to the membrane magnesium transporter (TC 1.A.67) family.|||Component of the ER membrane protein complex (EMC).|||Early endosome membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (By similarity). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable). May be involved Mg(2+) transport (PubMed:18057121).|||Up-regulated by low extracellular Mg(2+). http://togogenome.org/gene/10090:Fam131b ^@ http://purl.uniprot.org/uniprot/E9Q8P8|||http://purl.uniprot.org/uniprot/Q3TY60 ^@ Similarity ^@ Belongs to the FAM131 family. http://togogenome.org/gene/10090:Plcg2 ^@ http://purl.uniprot.org/uniprot/Q8CIH5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Membrane raft|||Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts constitutively with THEMIS2 (PubMed:27992403).|||Phosphorylated on tyrosine residues by BTK and SYK; upon ligand-induced activation of a variety of growth factor receptors and immune system receptors. Phosphorylation leads to increased phospholipase activity (By similarity). Phosphorylated on tyrosine residues by CSF1R.|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. http://togogenome.org/gene/10090:Ptch2 ^@ http://purl.uniprot.org/uniprot/O35595 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the patched family.|||Detected in 8.5 to 17.5 dpc embryos.|||Expressed in epithelial cells of the developing hair, tooth and whisker.|||Membrane|||Plays a role in the control of cellular growth (By similarity). May have a role in epidermal development. May act as a receptor for Sonic hedgehog (SHH). http://togogenome.org/gene/10090:Adgrf4 ^@ http://purl.uniprot.org/uniprot/A0A0D9SEG9|||http://purl.uniprot.org/uniprot/Q9D2L6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Expressed during embryonic development in the skin starting at embryonic day 12 with the formation of the basal layer of the skin.|||Expressed in squamous epithelia.|||Membrane|||Most adhesion GPCRs undergo autoproteolysis at the GPS domain. ADGRF2 is not autoproteolyzed at the GPS motif because of the lack of a consensus catalytic triad sequence within GPS domain.|||No visible phenotype.|||Orphan receptor. http://togogenome.org/gene/10090:Or8s5 ^@ http://purl.uniprot.org/uniprot/Q8VET7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krtap24-1 ^@ http://purl.uniprot.org/uniprot/G3X9A2|||http://purl.uniprot.org/uniprot/Q8CAZ5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Or1n1b ^@ http://purl.uniprot.org/uniprot/Q8VGK0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Setx ^@ http://purl.uniprot.org/uniprot/A2AKX3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA2/NAM7 helicase family.|||Chromosome|||Cytoplasm|||Expressed in cerebellum, hippocampus, olfactory bulb, Bergmann glial fibers, stellate cells and Purkinje cells. Expressed in the epithelial cells of the lens but not in mature lens fiber cells. Expressed in the retina (highly expressed in inner and outer segments of photoreceptors and outer plexiform layer cells but weakly expressed in the inner plexiform and ganglion cell layers). Expressed in the kidney.|||Homodimer (By similarity). Interacts with PER2; the interaction inhibits termination of circadian target genes (PubMed:22767893). Interacts with CHD4, POLR2A, PRKDC and TRIM28. Does not interact with C14orf178. Interacts with UBE2I. Interacts (via N-terminus domain) with EXOSC9 (via C-terminus region); the interaction enhances SETX sumoylation. Interacts with NCL (via N-terminus domain). Interacts with PABPN1, PABPC1 and SF3B1. Interacts with SMN1/SMN2 and POLR2A; SMN1/SMN2 recruits SETX to POLR2A (By similarity).|||Mice are viable. Male germ cells proceed normally from spermatogonia up to the meiotic pachytene stage but fail to enter into spermiogenesis and form mature spermatids (PubMed:23593030), resulting in male infertility. In particular, during spermatogenesis, male germ cells accumulated DNA:RNA hybrids (R-loops), meiotic DNA double-strand breaks, and fails to produce crossovers and meiotic sex chromosome inactivation (MSCI) (PubMed:23593030).|||Nucleus|||Probable RNA/DNA helicase involved in diverse aspects of RNA metabolism and genomic integrity. Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription. Contributes to the mRNA splicing efficiency and splice site selection. Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination (By similarity). Required for the 3' transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation (PubMed:22767893). Involved in DNA double-strand breaks damage response generated by oxidative stress. In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage (By similarity). Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI) (PubMed:23593030). Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis. May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription (By similarity).|||Sumoylated preferentially with SUMO2 or SUMO3.|||The N-terminus domain is necessary for S/G2 nuclear foci localization.|||The sequence differs from that shown because it is derived from pre-RNA.|||Ubiquitinated.|||axon|||growth cone|||nucleolus|||nucleoplasm|||telomere http://togogenome.org/gene/10090:Mbnl3 ^@ http://purl.uniprot.org/uniprot/Q8R003 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the muscleblind family.|||Cytoplasm|||High expression in proliferating myoblasts is strongly reduced in differentiated muscle cells.|||Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins (By similarity). Could inhibit terminal muscle differentiation, acting at approximately the time of myogenin induction.|||Nucleus http://togogenome.org/gene/10090:Dsg1a ^@ http://purl.uniprot.org/uniprot/Q61495 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to JUP/plakoglobin (By similarity). Interacts with PKP2 (By similarity).|||Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.|||Cytoplasm|||Expressed in embryo at 17 dpc.|||Expressed in testis.|||Nucleus|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Gnpda1 ^@ http://purl.uniprot.org/uniprot/O88958|||http://purl.uniprot.org/uniprot/Q3TKA0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by N-acetylglucosamine-6-phosphate (GlcNAc6P).|||Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.|||Catalyzes the reversible conversion of alpha-D-glucosamine 6-phosphate (GlcN-6P) into beta-D-fructose 6-phosphate (Fru-6P) and ammonium ion, a regulatory reaction step in de novo uridine diphosphate-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) biosynthesis via hexosamine pathway. Deamination is coupled to aldo-keto isomerization mediating the metabolic flux from UDP-GlcNAc toward Fru-6P. At high ammonium level can drive amination and isomerization of Fru-6P toward hexosamines and UDP-GlcNAc synthesis (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and their effects on hyaluronan synthesis that occur during tissue remodeling (By similarity). Seems to trigger calcium oscillations in mammalian eggs. These oscillations serve as the essential trigger for egg activation and early development of the embryo (By similarity).|||Cytoplasm|||Homohexamer.|||Widely expressed. Detected in brain, liver, kidney, muscle, ovary, testis, spermatids and spermatozoa. In spermatids, located close to the developing acrosome vesicle. In spermatozoa, found close to the acrosomal region. http://togogenome.org/gene/10090:Wdr53 ^@ http://purl.uniprot.org/uniprot/Q9DB94 ^@ Similarity ^@ Belongs to the WD repeat WDR53 family. http://togogenome.org/gene/10090:Slc32a1 ^@ http://purl.uniprot.org/uniprot/O35633 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals (PubMed:9395291, PubMed:26912364, PubMed:27601664, PubMed:16701208). The transport is equally dependent on the chemical and electrical components of the proton gradient (PubMed:9395291, PubMed:27601664). May also transport beta-alanine (By similarity). Acidification of GABAergic synaptic vesicles is a prerequisite for 4-aminobutanoate uptake (PubMed:27601664).|||Belongs to the amino acid/polyamine transporter 2 family.|||Brain and retina. Localized in horizontal cell tips at both rod and cone terminals.|||Chloride ions activate 4-aminobutanoate/H(+) transport.|||Cytoplasmic vesicle membrane|||Deficient mice exhibit embryonic lethality and a cleft palate and omphalocele.|||Juge et al. shows that SLC32A1 is a symporter of both 4-aminobutanoate or glycine or beta-alanine with Cl(-) that operates according an electrical gradient without the need for a chemical gradient (By similarity). However Farsi et al. and Egashira et al. confirm that SLC32A1 is an antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or glycine and exclude any coupling with chloride (PubMed:27601664, PubMed:26912364).|||Presynapse http://togogenome.org/gene/10090:Cndp2 ^@ http://purl.uniprot.org/uniprot/Q9D1A2 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M20A family.|||Binds 2 manganese ions per subunit.|||Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides (PubMed:31587987). Mediates threonyl dipeptide catabolism in a tissue-specific way (PubMed:31587987). Has high dipeptidase activity toward cysteinylglycine, an intermediate metabolite in glutathione metabolism (By similarity). Metabolizes N-lactoyl-amino acids, both through hydrolysis to form lactic acid and amino acids, as well as through their formation by reverse proteolysis (By similarity). Plays a role in the regulation of cell cycle arrest and apoptosis (By similarity).|||Cytoplasm|||Highly expressed in the parafascicular nucleus of the thalamus, tuberomammillary nucleus of the hypothalamus and the mitral cell layer of the olfactory bulb.|||Homodimer.|||Inhibited by bestatin. http://togogenome.org/gene/10090:Atpaf1 ^@ http://purl.uniprot.org/uniprot/H3BLL2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP11 family.|||Mitochondrion http://togogenome.org/gene/10090:Psd2 ^@ http://purl.uniprot.org/uniprot/Q6P1I6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PSD family.|||Cell membrane|||Cleavage furrow|||ruffle membrane http://togogenome.org/gene/10090:Pros1 ^@ http://purl.uniprot.org/uniprot/Q08761|||http://purl.uniprot.org/uniprot/Q3TR66 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Plasma.|||Secreted|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Golm1 ^@ http://purl.uniprot.org/uniprot/Q3TIZ8|||http://purl.uniprot.org/uniprot/Q91XA2 ^@ Caution|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GOLM family.|||Glycosylated.|||Interacts with DYM.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Membrane|||Phosphorylation sites are present in the extracellular medium.|||Unknown. Cellular response protein to viral infection.|||Up-regulated in response to viral infection.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Tmem88 ^@ http://purl.uniprot.org/uniprot/Q9D0N8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM88 family.|||Cell membrane|||Inhibits the Wnt/beta-catenin signaling pathway. Crucial for heart development and acts downstream of GATA factors in the pre-cardiac mesoderm to specify lineage commitment of cardiomyocyte development (By similarity).|||Interacts (via C-terminus) with DVL1. http://togogenome.org/gene/10090:Hic1 ^@ http://purl.uniprot.org/uniprot/Q9R1Y5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated on several residues, including Lys-333. Lys-333 is deacetylated by SIRT1 (By similarity).|||Belongs to the krueppel C2H2-type zinc-finger protein family. Hic subfamily.|||Expression is first detected in the embryo after 9 dpc. In the embryo, expression is found in restricted regions of somite derivatives, limb anlagen and cranio-facial mesenchyme. In the fetus, it is additionally expressed in mesenchymes apposed to precartilaginous condensations, at many interfaces to budding epithelia of inner organs, and weakly in muscles.|||Impaired development resulting in embryonic and perinatal lethality (PubMed:10655551, PubMed:12539045). Serious developmental anomalies including acrania, exencephaly, cleft palate, omphalocele and limb abnormalities (PubMed:10655551). Mice disrupted in the germ line for only one allele of Hic1 develop many different spontaneous malignant tumors, including a predominance of epithelial cancers in males and lymphomas and sarcomas in females (PubMed:12539045). The complete loss of Hic1 function in the heterozygous mice seems to involve dense methylation of the promoter of the remaining wild-type allele (PubMed:12539045).|||Nucleus|||Self-associates (By similarity). Interacts with HIC2 (By similarity). Interacts with CTBP1 and CTBP2 (By similarity). Interacts with TCF7L2 and ARID1A (By similarity). Interacts with MTA1 and MBD3; indicative for an association with the NuRD complex (By similarity). Interacts with SIRT1 (PubMed:16269335).|||Sumoylated on Lys-333 by a PIAS family member, which enhances interaction with MTA1, positively regulates transcriptional repression activity and is enhanced by HDAC4.|||The BTB domain inhibits the binding to a single consensus binding site, but mediates cooperative binding to multiple binding sites.|||Transcriptional repressor (PubMed:18347096). Recognizes and binds to the consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3' (By similarity). May act as a tumor suppressor (PubMed:16269335, PubMed:18347096). Involved in development of head, face, limbs and ventral body wall (PubMed:10655551). Involved in down-regulation of SIRT1 and thereby is involved in regulation of p53/TP53-dependent apoptotic DNA-damage responses (PubMed:16269335). The specific target gene promoter association seems to be depend on corepressors, such as CTBP1 or CTBP2 and MTA1 (By similarity). In cooperation with MTA1 (indicative for an association with the NuRD complex) represses transcription from CCND1/cyclin-D1 and CDKN1C/p57Kip2 specifically in quiescent cells (By similarity). Involved in regulation of the Wnt signaling pathway probably by association with TCF7L2 and preventing TCF7L2 and CTNNB1 association with promoters of TCF-responsive genes (By similarity). Seems to repress transcription from E2F1 and ATOH1 which involves ARID1A, indicative for the participation of a distinct SWI/SNF-type chromatin-remodeling complex (By similarity). Probably represses transcription from ACKR3, FGFBP1 and EFNA1 (By similarity).|||Ubiquitously expressed with highest levels in heart and lung. http://togogenome.org/gene/10090:Ccl27b ^@ http://purl.uniprot.org/uniprot/Q9Z1X0 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic factor that attracts skin-associated memory T-lymphocytes. May play a role in mediating homing of lymphocytes to cutaneous sites. May play a role in cell migration during embryogenesis. Nuclear forms may facilitate cellular migration by inducing cytoskeletal relaxation. Binds to CCR10.|||Expressed during development.|||Isoform 1 is predominantly expressed in placenta and weakly in skin. Isoform 2 is predominantly expressed in testes and brain, weakly in kidney and liver and even lower in heart and muscle. Low expression of both isoforms in other tissues.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Monomer, dimer, and tetramer. Heparin avidly promotes oligomerization. Interacts with TNFAIP6 (via Link domain).|||Nucleus|||Secreted http://togogenome.org/gene/10090:Or4f14d ^@ http://purl.uniprot.org/uniprot/Q8VG12 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sox3 ^@ http://purl.uniprot.org/uniprot/A2AM37|||http://purl.uniprot.org/uniprot/Q5RKW0 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Noxa1 ^@ http://purl.uniprot.org/uniprot/Q8CJ00 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NCF2/NOXA1 family.|||Cell membrane|||Cytoplasm|||Functions as an activator of NOX1, a superoxide-producing NADPH oxidase. Functions in the production of reactive oxygen species (ROS) which participate in a variety of biological processes including host defense, hormone biosynthesis, oxygen sensing and signal transduction. May also activate CYBB/gp91phox and NOX3.|||NOX1, NOXA1, NOXO1, RAC1 and CYBA forms a functional multimeric complex supporting ROS production. Interaction with YWHAZ prevents the interaction of NOXA1 with NOXO1 and RAC1 and its targeting to membranes, hence reducing its ability to activate NOX1. Interacts (via N-terminus) with SH3PXD2A and SH3PXD2B; the interaction is direct (By similarity).|||The SH3 domain mediates interaction with NOXO1 and NCF1 and has autoregulatory function.|||The TPR repeats mediate interaction with RAC1.|||Widely expressed with a tissue distribution similar to the one of NOX1. Detected in colon, uterus, prostate, small intestine, stomach, lung, thyroid, aorta, inner ear and salivary glands. Expressed in colon, small intestine and aortic smooth muscle cells (at protein level). http://togogenome.org/gene/10090:Or8b36 ^@ http://purl.uniprot.org/uniprot/Q8VF64 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Iglon5 ^@ http://purl.uniprot.org/uniprot/Q8HW98 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. IgLON family.|||Secreted http://togogenome.org/gene/10090:Arf6 ^@ http://purl.uniprot.org/uniprot/P62331|||http://purl.uniprot.org/uniprot/Q3U0D7 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation is generally mediated by guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by GTPases activating protein (GAP). Inactivated by ACAP1 and ACAP2 (By similarity). Activated by NGF via NTRK1 (By similarity).|||Belongs to the small GTPase superfamily. Arf family.|||Cell membrane|||Cleavage furrow|||Early endosome membrane|||Endosome membrane|||GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11950392). Required for normal completion of mitotic cytokinesis. Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension. Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization. Regulates surface levels of adherens junction proteins such as CDH1 (PubMed:29420262, PubMed:20080746). Required for NTRK1 sorting to the recycling pathway from early endosomes (By similarity).|||GTP-bound form is myristoylated on Lys-3 by NMT1 and NMT2, allowing ARF6 to remain on membranes during the GTPase cycle, thereby promoting its activity. GDP-bound inactive form is demyristoylated on Lys-3 by SIRT2 at early endosomes or endocytic recycling compartment to allow its efficient activation by a guanine exchange factor (GEF) after GDP release.|||Interacts (when activated) with GGA1, GGA2 and GGA3; the interaction is required for proper subcellular location of GGA1, GGA2 and GGA3 (PubMed:11950392, PubMed:22522702). Interacts with ARHGAP21, ASAP2, HERC1, PIP5K1C and UACA. Interacts with NCS1/FREQ at the plasma membrane. Interacts with RAB11FIP3. Interacts with USP6 (via Rab-GAP TBC domain). Interacts with ECPAS. Interacts with TBC1D24. Interacts with MICALL1. Interacts with CYTH3 (By similarity). Interacts with KIF23, forming heterodimers and heterotetramers. Interacts with SPAG9 and RAB11FIP4 (PubMed:22522702). Interacts with C9orf72 (PubMed:27723745). Interacts (GTP-bound form) with TJAP1/PILT (PubMed:22841714).|||Midbody ring|||Recycling endosome membrane|||Widely expressed.|||cytosol|||filopodium membrane|||ruffle|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ralbp1 ^@ http://purl.uniprot.org/uniprot/Q62172 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Could also function as a primary ATP-dependent active transporter for glutathione conjugates of electrophiles. May also actively catalyze the efflux of a wide range of substrates including xenobiotics like doxorubicin (DOX) contributing to cell multidrug resistance.|||Interacts with the GTP-bound form of RALA (via effector domain); during mitosis, recruits RALBP1 to the mitochondrion where it promotes DNM1L phosphorylation and mitochondrial fission. Interacts with DNM1L; mediates its mitotic kinase cyclin B-CDK1-mediated phosphorylation during mitosis to promote mitochondrial fission. Interacts with the mitotic kinase cyclin B-CDK1 during mitosis. Interacts with the GTP-bound form of RALB (via effector domain) (By similarity). Interacts with REPS1; the interaction is direct and does not affect RALA-binding nor GTPase activator activity of RALBP1 (PubMed:9395447). Interacts with REPS2; the interaction is direct and does not affect RALA-binding nor GTPase activator activity of RALBP1 (By similarity). Interacts with EPN1, NUMB and TFAP2A during interphase and mitosis. Interacts with AP2M1; as part of the AP2 complex (PubMed:10910768). Interacts with CDC42. Interacts with RAC1 (By similarity).|||May undergo proteolytic cleavage to give peptides which reassemble to form a transporter complex.|||Mitochondrion|||Multifunctional protein that functions as a downstream effector of RALA and RALB. As a GTPase-activating protein/GAP can inactivate CDC42 and RAC1 by stimulating their GTPase activity (PubMed:8570186). As part of the Ral signaling pathway, may also regulate ligand-dependent EGF and insulin receptors-mediated endocytosis. During mitosis, may act as a scaffold protein in the phosphorylation of EPSIN/EPN1 by the mitotic kinase cyclin B-CDK1, preventing endocytosis during that phase of the cell cycle. During mitosis, also controls mitochondrial fission as an effector of RALA. Recruited to mitochondrion by RALA, acts as a scaffold to foster the mitotic kinase cyclin B-CDK1-mediated phosphorylation and activation of DNM1L (By similarity).|||Nucleus|||The Rho-GAP domain mediates the GTPase activator activity toward CDC42.|||Tyrosine-phosphorylated upon stimulation of cells with EGF.|||Ubiquitous. The highest level of expression was observed in ovaries and skeletal muscle, whereas the lowest was found in spleen, liver and peripheral blood leukocytes.|||cytosol|||spindle pole http://togogenome.org/gene/10090:Krt17 ^@ http://purl.uniprot.org/uniprot/Q9QWL7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Expressed strongly in outer root sheath and medulla region of hair follicle and in the early differentiating epithelial cells (trichocytes) within the hair bulb region. Weak expression in the matrix cells of hair bulb. Also present in the sweat gland within the skin, vibrissae follicle, salivary gland, tooth and thymus.|||Expression first occurs in a subset of epithelial cells within the single-layered, undifferentiated ectoderm of embryonic day 10.5 mouse fetuses (PubMed:9786956). In the ensuing 48 hours, K17-expressing cells give rise to placodes, the precursors of ectoderm-derived appendages (hair, glands, and tooth), and to periderm (PubMed:9786956). Expressed in hair follicles and in the basal and suprabasal layers of the interfollicular epidermis at birth (PubMed:11408584).|||Heterodimer of a type I and a type II keratin. KRT17 associates with KRT6 isomers (KRT6A or KRT6B) (By similarity). Interacts with TRADD and SFN.|||Induced in damaged or stressed epidermis and by interferon-gamma. Up-regulated by LEF1.|||Phosphorylation at Ser-44 occurs in a growth- and stress-dependent fashion in skin keratinocytes, it has no effect on filament organization.|||Severe alopecia during the first week postbirth, correlating with hair fragility, alterations in follicular histology, and apoptosis in matrix cells.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (PubMed:14714564, PubMed:16702408). Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state (PubMed:16702408). Modulates the function of TNF-alpha in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway (PubMed:16710422). Involved in tissue repair. May be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial 'stem cells'. Acts as a promoter of epithelial proliferation by acting a regulator of immune response in skin: promotes Th1/Th17-dominated immune environment contributing to the development of basaloid skin tumors (PubMed:20871598). May act as an autoantigen in the immunopathogenesis of psoriasis, with certain peptide regions being a major target for autoreactive T-cells and hence causing their proliferation. http://togogenome.org/gene/10090:Skint1 ^@ http://purl.uniprot.org/uniprot/A7TZE6 ^@ Function|||Miscellaneous|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin and thymus.|||Humans and chimpanzees have a SKINT1-like (SKINT1L) gene with multiple inactivating mutations. All hominoid species have a common inactivating mutation, but that Old World monkeys such as olive baboons, green monkeys, cynomolgus macaques and rhesus macaques have apparently functional SKINT1L sequences, indicating that SKINT1L is inactivated in a common ancestor of hominoids.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus. Plays a central role in mediating key epithelial-immune interactions by being involved in the selection of Vgamma5(+)Vdelta1(+) T-cells, which constitute 90% of epidermal gammadelta T-cells.|||Membrane|||The strain FVB/NTac displays a selective deficiency for epidermal Vgamma5(+)Vdelta1(+) T-cells due to a mutation that creates premature codon stop at position 324. http://togogenome.org/gene/10090:Bcas1 ^@ http://purl.uniprot.org/uniprot/Q80YN3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in the brain and, more specifically, in oligodendrocytes. Expressed in the Schwann cells (at protein level).|||Homodimer. Interacts with DYNLL1 and DYNLL2.|||Mice display hypomyelination, schizophrenia-like behavioral abnormalities and a tendency toward reduced anxiety-like behaviors and up-regulation of inflammatory genes in the brain.|||Required for myelination. http://togogenome.org/gene/10090:Scart2 ^@ http://purl.uniprot.org/uniprot/B3F5L4|||http://purl.uniprot.org/uniprot/B3F5L5|||http://purl.uniprot.org/uniprot/Q8C9T4 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:H2bc6 ^@ http://purl.uniprot.org/uniprot/Q6ZWY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Tslp ^@ http://purl.uniprot.org/uniprot/Q9JIE6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytokine that induces the release of T-cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells. Can induce allergic inflammation by directly activating mast cells (By similarity).|||Interacts with a receptor composed of CRLF2 and IL7R. Binding of TSLP to CRLF2/TSLPR is a mechanistic prerequisite for recruitment of IL7R to the high-affinity ternary complex.|||Secreted http://togogenome.org/gene/10090:Cpped1 ^@ http://purl.uniprot.org/uniprot/Q8BFS6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the metallophosphoesterase superfamily. CPPED1 family.|||Binds 2 divalent metal cations.|||Cytoplasm|||Protein phosphatase that dephosphorylates AKT family kinase specifically at 'Ser-473', blocking cell cycle progression and promoting cell apoptosis. May play an inhibitory role in glucose uptake by adipocytes (By similarity). http://togogenome.org/gene/10090:Ccna1 ^@ http://purl.uniprot.org/uniprot/Q61456 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family. Cyclin AB subfamily.|||CCNA1 -/- males are sterile due to a block of spermatogenesis before the first meiotic division, whereas females are normal.|||In male germ cells just prior to or during the first, but not the second meiotic division.|||Interacts with INCA1 and KLHDC9 (By similarity). Interacts with the CDK2 and CDC2 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Found in a complex with CDK2, CABLES1 and CCNE1.|||May be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells.|||Nucleus|||Polyubiquitinated via 'Lys-11'-linked ubiquitin by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome. Deubiquitinated and stabilized by USP37 enables entry into S phase (By similarity).|||Testis and ovaries.|||spindle http://togogenome.org/gene/10090:Dnah7a ^@ http://purl.uniprot.org/uniprot/E9Q0T8 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Fam216a ^@ http://purl.uniprot.org/uniprot/Q9DB54 ^@ Similarity ^@ Belongs to the FAM216 family. http://togogenome.org/gene/10090:Stil ^@ http://purl.uniprot.org/uniprot/Q60988 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Death during embryonic development between days 8.5 and 10.5. Embryos are reduced in size and display delayed development. They have axial midline defects, and randomized cardiac looping. The midline sonic hedgehog signaling is blocked in these mice.|||Down-regulated during cell terminal differentiation. Accumulates during G2 phase and falls at completion of the cell cycle.|||Homodimer (By similarity). Interacts with PIN1 via its WW domain. This interaction is dependent on Stil mitotic phosphorylation (PubMed:16024801). Interacts with CENPJ. Interacts with RBM14 and this interaction interferes with the interaction of STIL with CENPJ. Forms a complex with CENPJ and SASS6 (By similarity).|||Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1. Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CENPJ to the base of the procentriole to initiate procentriole assembly (By similarity).|||Phosphorylated following the activation of the mitotic checkpoint.|||Ubiquitinated.|||Ubiquitously expressed in adult and fetal tissues. Highly expressed in hematopoietic tissues such as thymus, bone marrow and spleen.|||centriole|||cytosol http://togogenome.org/gene/10090:Sc5d ^@ http://purl.uniprot.org/uniprot/O88822 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sterol desaturase family.|||Catalyzes a dehydrogenation to introduce C5-6 double bond into lathosterol in cholesterol biosynthesis.|||Endoplasmic reticulum membrane|||The histidine box domains may contain the active site and/or be involved in metal ion binding. http://togogenome.org/gene/10090:Plekhf2 ^@ http://purl.uniprot.org/uniprot/Q91WB4 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early endosome membrane|||Endoplasmic reticulum|||Expressed in brain, stomach and thymus, as well as in kidney, spleen, and skeletal muscle. Also expressed in peripheral blood mononuclear cells and dendritic cells.|||May interact with EEA1.|||May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport (By similarity). Enhances cellular sensitivity to TNF-induced apoptosis.|||The PH and FYVE domains may be important for TNF-induced localization to the endoplasmic reticulum and for enhanced cellular sensitivity to TNF-induced apoptosis. The FYVE domain is important for binding to the endosomal membrane (By similarity).|||Up-regulated by TNF, bacterial lipopolysaccharides (LPS) and phorbol myristate acetate (PMA) (at protein level). http://togogenome.org/gene/10090:Vmn1r62 ^@ http://purl.uniprot.org/uniprot/Q8R2C0|||http://purl.uniprot.org/uniprot/Q9EPT0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H3c1 ^@ http://purl.uniprot.org/uniprot/P68433 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (By similarity).|||This histone is only present in mammals.|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Immp2l ^@ http://purl.uniprot.org/uniprot/Q8BPT6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S26 family. IMP2 subfamily.|||Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO (By similarity).|||Heterodimer of 2 subunits, IMMPL1 and IMMPL2.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cdca8 ^@ http://purl.uniprot.org/uniprot/Q8BHX3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the borealin family.|||Citrullinated by PADI4.|||Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. In the complex, it may be required to direct the CPC to centromeric DNA. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment (By similarity).|||Cytoplasm|||May form homooligomers and homodimers. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and BIRC5 (By similarity). Interacts with SENP3, UBE2I and RANBP2. Interacts (phosphorylated) with SGO1 and SGO2; the association is dependent on CDK1 (By similarity).|||Phosphorylated by TTK, essentially at Thr-94. Phosphorylation (probably by CDK1) promotes targeting of the CPC to centromeric DNA.|||Sumoylated by UBE2I and RANBP2. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3 (By similarity).|||The C-terminal region (aa 216-289) represents the dimerization motif.|||centromere|||nucleolus|||spindle http://togogenome.org/gene/10090:Gps2 ^@ http://purl.uniprot.org/uniprot/Q921N8 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:25519902). Interacts (when sumoylated at Lys-71) with TBL1X; leading to protect GPS2 from degradation by the proteasome (PubMed:26070566). Interacts with UBE2N; leading to inhibit UBE2N/Ubc13 activity (PubMed:22424771). Interacts with TRAF1 (PubMed:22424771). Interacts with TRAF2 (PubMed:22424771). Interacts with TRAF6 (PubMed:22424771). Interacts with PPARG (when in the liganded conformation) (PubMed:25519902). Interacts with (sumoylated) NR1H2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (By similarity). Interacts with (sumoylated) NR5A2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (By similarity). Interacts with NR1H3 (By similarity). Interacts with RFX4 (PubMed:18218630). Interacts with ANKRD26 (By similarity).|||Embryonic lethality (PubMed:25519902). Embryonic fibroblast cells show reduced corepressor function of the N-CoR complex for PPARG, leading to constitutive activation of PPARG target genes and spontaneous adipogenesis of the cells (PubMed:25519902). Conditional knockout mice lacking Gps2 in B-cells show developmental defects at multiple stages of B-cell differentiation, caused by of aberrant activation of 'Lys-63'-linked ubiquitination events and altered gene expression programs downstream of the misregulated signaling pathways (PubMed:28039360). Conditional knockout mice lacking Gps2 in macrophages show inappropriate corepressor complex function, leading to enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals (PubMed:27270589). Conditional knockout mice lacking Gps2 in adipose tissues show obesity associated with constitutive insulin signaling, increased lipid deposition in the white adipose tissue and improved systemic insulin sensitivity (PubMed:28123943). Conditional knockout mice lacking Gps2 in adipose tissues display reduced mitochondrial content in brown adipose tissue (PubMed:29499132).|||Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'-linked ubiquitination (PubMed:22424771, PubMed:24953653, PubMed:28039360, PubMed:28123943, PubMed:29499132). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:18218630, PubMed:24953653, PubMed:25519902, PubMed:27270589, PubMed:28039360). Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone H3 'Lys-9' (H3K9) demethylation (PubMed:22666460, PubMed:24953653). Promotes cholesterol efflux by acting as a transcription coactivator (By similarity). Acts as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B-cell antigen receptors (BCRs) signaling pathways (PubMed:28039360). Acts as a key mediator of mitochondrial stress response: in response to mitochondrial depolarization, relocates from the mitochondria to the nucleus following desumoylation and specifically promotes expression of nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG (PubMed:25519902). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (PubMed:27270589). Plays an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins, thereby preventing N-Cor corepressor complex dissociation (By similarity). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways (PubMed:22424771, PubMed:28123943). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the pro-inflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (PubMed:22424771). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (PubMed:28123943). Able to suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction (By similarity).|||Methylated at Arg-312 and Arg-323 by PRMT6. Methylation at Arg-323 protects from degradation by the proteasome.|||Mitochondrion|||Nucleus|||Sumoylation regulates its subcellular location (PubMed:26070566, PubMed:29499132). Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the cytoplasm and the nucleus (By similarity). Sumoylation at Lys-71 is required for interaction with TBL1X (PubMed:26070566). Sumoylated at Lys-45 and Lys-71 in mitochondrion (PubMed:29499132). Desumoylation by SENP1 leads to relocation from the mitochondria to the nucleus (PubMed:29499132).|||Ubiquitinated at the C-terminus by SIAH2; leading to its degradation by the proteasome. Interaction with TBL1X and methylation at Arg-323 protect GPS2 against ubiquitination and degradation.|||cytosol http://togogenome.org/gene/10090:Dynlt1f ^@ http://purl.uniprot.org/uniprot/P51807|||http://purl.uniprot.org/uniprot/Q9DAS3 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Binds to transport cargos and is involved in apical cargo transport such as rhodopsin-bearing vesicles in polarized epithelia (By similarity). May also be a accessory component of axonemal dynein. Plays an important role in male germ cell development and function. Candidate for involvement in male sterility.|||Belongs to the dynein light chain Tctex-type family.|||Cytoplasm|||First abundantly expressed at the pachytene stage of meiosis and persists throughout spermatogenesis.|||Golgi apparatus|||High level in testis (germ cell-specific). Expressed in sperm (at protein level). 200-fold lower in liver, brain, heart, spleen, and kidney. Levels in thymus and two embryonal carcinoma cell lines were several-fold higher than this low constitutive level.|||Homodimer (Probable). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. DYNLT1 and DYNLT3 compete for association with dynein IC (DYNC1I1 or DYNC1I2). Self-associates. Interacts with RHO (By similarity). Interacts with DYNC1I1 and DYNC1I2. Interacts with DOC2A, DOC2B and SCN10A. Interacts with PVR. Interacts with SVIL isoform 2. Interacts with GNB1; the interaction occurs in presence of guanine nucleotide-binding protein G(T) subunit gamma; the interaction diminishes the association of DYNLT1 with dynein IC (DYNC1I1 or DYNC1I2). Interacts with GNB2, GNB3 and GNB5; the interactions occur in presence of guanine nucleotide-binding protein G(T) subunit gamma. Interacts with ACVR2B and ARHGEF2 (By similarity). Interacts with DNAI4 (PubMed:30060180).|||Phosphorylated by BMPR2. The phosphorylation status is proposed to regulate the association with the cytoplasmic dynein complex and may have role in cytoplasmic dynein cargo release (By similarity).|||Plays a role in neuronal morphogenesis; the function is independent of cytoplasmic dynein and seems to be coupled to regulation of the actin cytoskeleton by enhancing Rac1 activity. The function in neurogenesis may be regulated by association with a G-protein beta-gamma dimer. May function as a receptor-independent activator of heterotrimeric G-protein signaling; the activation appears to be independent of a nucleotide exchange. Plays a role in regulating neurogenesis; inhibits the genesis of neurons from precursor cells during cortical development presumably by antagonizing ARHGEF2. Unrelated to the role in retrograde microtubule-associated movement may play a role in the dimerization of cytoplasmic proteins/domains such as for ACVR2B. Binds to the cytoplasmic domain of ACVR2B and, in vitro, inhibits ACVR2B signaling. Involved in the regulation of mitotic spindle orientation.|||spindle http://togogenome.org/gene/10090:Ackr1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J4|||http://purl.uniprot.org/uniprot/Q9QUI6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1 and TARC. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels (By similarity).|||Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1 and TARC. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.|||Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.|||Early endosome|||Expressed in liver and brain.|||Membrane|||Recycling endosome http://togogenome.org/gene/10090:Tada1 ^@ http://purl.uniprot.org/uniprot/Q99LM9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TADA1 family.|||Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9.|||Nucleus|||Probably involved in transcriptional regulation. http://togogenome.org/gene/10090:Cbln2 ^@ http://purl.uniprot.org/uniprot/Q8BGU2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a synaptic organizer in specific subsets of neurons in the brain (PubMed:29691328, PubMed:21410790). Essential for long-term maintenance but not establishment of excitatory synapses (PubMed:29691328, PubMed:30287486).|||Expressed in various brain regions with higher levels in the olfactory bulb, cerebral cortex, certain thalamic and hypothalamic nuclei, superior and inferior colliculi and some brainstem nuclei. Highly expressed in the dorsal medial habenula.|||Homohexamer; disulfide-linked homotrimers. The trimers are assembled via the globular C1q domains. The trimers associate via N-terminal cysteine residues to form disulfide-linked hexamers (By similarity). May form homooligomers or heterooligomers with CBLN1 and CBLN3 prior to secretion (PubMed:29782851). Once secreted, does not interact with other CBLN family members. Interacts with GRID2, and more weakly with GRID1. Interacts with NRXN1 and NRXN2 long and short isoforms produced by alternative promoter usage (PubMed:21410790, PubMed:22220752, PubMed:29782851). Weakly interacts with NRXN3 short isoform and not at all with NRXN3 long isoform (PubMed:22220752, PubMed:29782851).|||In the developing brain, expressed as early as 10-13 dpc. Expression level peaks at 18 dpc and gradually decreases afterwards.|||Mice show impaired synaptic transmission within 3 weeks in interpeduncular target neurons whereas significant decrease in both the synapse density and size seen only after 3 months (PubMed:30287486). Display impaired passive avoidance learning, spatial learning and short-term memory (PubMed:30287486). Double CBLN1 and CBLN2 knockout mice exhibit gait abnormalities, impairments in balance and coordination and develop seizures (PubMed:29691328). Synapse density in the hippocampus is normal in 1-2 months old mice, but severely decreased in 6 month old mice (PubMed:29691328). Triple CBLN1, CBLN2 and CBLN4 knockout mice exhibit impairments in sensory processing and sensorimotor gating, in addition to severe motor deficits, seizures and reduced synapse density in the hippocampus of aging mice (PubMed:29691328).|||Secreted http://togogenome.org/gene/10090:Adh6a ^@ http://purl.uniprot.org/uniprot/E9Q5Z6|||http://purl.uniprot.org/uniprot/Q9D932 ^@ Similarity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. http://togogenome.org/gene/10090:Nr5a2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YY04|||http://purl.uniprot.org/uniprot/P45448|||http://purl.uniprot.org/uniprot/Q1WLP7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR5 subfamily.|||Binds DNA as a monomer (By similarity). Interacts with GRIP1, NCOA2 and NR0B2 (PubMed:12820970, PubMed:15976031). Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (By similarity).|||Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development (By similarity). Activates the transcription of CYP2C38 (PubMed:30555544).|||Nucleus|||Sumoylated by SUMO1 at Lys-289 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation. http://togogenome.org/gene/10090:Ppbp ^@ http://purl.uniprot.org/uniprot/Q9EQI5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Secreted http://togogenome.org/gene/10090:Syt10 ^@ http://purl.uniprot.org/uniprot/Q9R0N4 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.|||Ca(2+) sensor specifically required for the Ca(2+)-dependent exocytosis of secretory vesicles containing IGF1 in neurons of the olfactory bulb (PubMed:21496647). Exocytosis of IGF1 is required for sensory perception of smell (PubMed:21496647). Not involved in Ca(2+)-dependent synaptic vesicle exocytosis (PubMed:21496647). Acts through Ca(2+) and phospholipid binding to the C2 domain: Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity).|||Highly expressed in the olfactory bulb.|||Homodimer; disulfide-linked via the cysteine motif (PubMed:10531343). Can also form heterodimers with SYT3, SYT6, SYT7 and SYT9 (PubMed:10531343, PubMed:10531344, PubMed:10871604).|||Impaired food-finding behaviors due to defects in sensory perception of smell. Decreased number of olfactory bulb synapses in the external plexiform layer, but not the glomerular layer, of the olfactory bulb. The size and dendritic arborization of olfactory bulb neurons are decreased, but not the synapse density per dendritic length. Defects are due to impaired exocytosis of IGF1 in neurons of the olfactory bulb.|||The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds.|||The first C2 domain mediates Ca(2+)-dependent phospholipid binding.|||secretory vesicle membrane http://togogenome.org/gene/10090:Hoxc9 ^@ http://purl.uniprot.org/uniprot/P09633 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Abd-B homeobox family.|||Interacts with Geminin/GMNN, which inhibits transcriptional activity.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Cdh15 ^@ http://purl.uniprot.org/uniprot/P33146 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. M-cadherin is part of the myogenic program and may provide a trigger for terminal muscle differentiation.|||Cell membrane|||Skeletal muscle.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Ctla2a ^@ http://purl.uniprot.org/uniprot/P12399 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Not known, expressed in activated T-cell.|||Secreted|||To the propeptide regions of cysteine proteases. http://togogenome.org/gene/10090:Daam2 ^@ http://purl.uniprot.org/uniprot/Q80U19 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the formin homology family.|||Conditional knockout mice lacking Daam2 in myocardial cells do not show any heart defects. Conditional knockout mice lacking Daam1 and Daam2 in myocardial cells show cardiomyopathy, which is stronger than with a single Daam1 deletion.|||Expressed in the embryonic myocardium: not expressed in the myocardium at 9.5 dpc but is present in epicardial cells. At 10.5 dpc, expressed in the mesenchyme surrounding the ventral foregut and in regions enriched in cardiac progenitors, as well as the epicardium and lining of the pericardial cavity. By 12.5 dpc, expressed throughout the myocardium and ventricular trabeculae.|||In early embryogenesis, expression is confined to embryonic ectoderm. Highly dynamic expression in later stages of gastrulation. In early somite stages, detected in posterior node and persists until 9-10 somites have developed when expression is concentrated in the chordoneural hinge. During organogenesis, expressed in the CNS, PNS, liver primordia, limb buds and genital tubercle.|||Interacts with DVL3. Interacts with INF2 (By similarity).|||Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system (PubMed:22227309, PubMed:24091014, PubMed:25754822). Acts downstream of Wnt ligands and upstream of beta-catenin (CTNNB1) (PubMed:22227309, PubMed:25754822). Required for canonical Wnt signaling pathway during patterning in the dorsal spinal cord by promoting the aggregation of Disheveled (Dvl) complexes, thereby clustering and formation of Wnt receptor signalosomes and potentiating Wnt activity (PubMed:22227309). During dorsal patterning of the spinal cord, inhibits oligodendrocytes differentiation via interaction with PIP5K1A (PubMed:25754822). Also regulates non-canonical Wnt signaling pathway (PubMed:24091014). Acts downstream of PITX2 in the developing gut and is required for left/right asymmetry within dorsal mesentery: affects mesenchymal condensation by lengthening cadherin-based junctions through WNT5A and non-canonical Wnt signaling, inducing polarized condensation in the left dorsal mesentery necessary to initiate gut rotation (PubMed:24091014). Together with DAAM1, required for myocardial maturation and sarcomere assembly (PubMed:26526197). Is a regulator of actin nucleation and elongation, filopodia formation and podocyte migration (By similarity).|||Partially unspliced pre-RNA.|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity). http://togogenome.org/gene/10090:Prdm4 ^@ http://purl.uniprot.org/uniprot/A0A1X7SB67|||http://purl.uniprot.org/uniprot/Q80V63 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||May function as a transcription factor involved in cell differentiation.|||Nucleus http://togogenome.org/gene/10090:Slc18a1 ^@ http://purl.uniprot.org/uniprot/Q32XG7|||http://purl.uniprot.org/uniprot/Q8R090 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Vesicular transporter family.|||Detected in adrenal medulla, and brain (at protein level). In brain, specifically found in the medulla oblongata, pons, prefrontal cortex, striatum, dentate gyrus and hippocampus (at protein level).|||Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports catecholamines and indolamines with higher affinity for serotonin (PubMed:21712771). Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates presynaptic monoaminergic vesicle transport in the amygdala and prefrontal brain regions related with emotion processing in response to environmental stimuli (By similarity).|||Increased apoptosis and reduced neurogenesis in the hippocampus. Spatial memory formation is mildly impaired.|||Inhibited by reserpine, and the proton ionophore carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP).|||Membrane|||secretory vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Taar4 ^@ http://purl.uniprot.org/uniprot/Q5QD15 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar4 show an absence of aversion to low concentrations of volatile amines and to the odor of predator urine.|||Olfactory receptor specific for 2-phenylethylamine, a trace amine present at high concentration in the urine of carnivore species, playing a key role in fear and avoidance responses. 2-phenylethylamine acts as a kairomone in the chemical detection of carnivore odor and triggers fear in mice. This receptor is probably mediated by the G(s)-class of G-proteins which activate adenylate cyclase.|||Specifically expressed in neurons of the olfactory epithelium, to discrete glomeruli predominantly localized to a confined bulb region. Present in the dorsal area of the main olfactory epithelium. http://togogenome.org/gene/10090:Adprs ^@ http://purl.uniprot.org/uniprot/Q8CG72 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (By similarity). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (By similarity). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (By similarity). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (By similarity). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:24191052, PubMed:30830864). Also hydrolyzes free poly(ADP-ribose) in mitochondria (By similarity). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (By similarity). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (By similarity).|||Belongs to the ADP-ribosylglycohydrolase family.|||Binds 2 magnesium ions per subunit.|||Chromosome|||Cytoplasm|||Knockout mice are phenotypically normal and fertile (PubMed:30830864). 1 hour induced brain ischemia results in 100% fatality within 24 hours (PubMed:30830864). 30 minutes of induced brain ischemia results in an increase in infarct size in the cortex, hippocampus, and striatum (PubMed:30830864). Increased number of cortical neurons with nucleus-accumulated poly(ADP-ribose) and higher abundance of poly(ADP-ribose) in general (PubMed:30830864).|||Mitochondrion matrix|||Monomer.|||Nucleus|||The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-47) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-47 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose.|||Ubiquitous. http://togogenome.org/gene/10090:Abcb10 ^@ http://purl.uniprot.org/uniprot/Q9JI39 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in the liver but not in non-hematopoietic tissues of 13 dpc embryos.|||Belongs to the ABC transporter superfamily. ABCB family. Mitochondrial peptide exporter (TC 3.A.1.212) subfamily.|||By transcription factor GATA-1 during erythroid differentiation and in vitro, by DMSO during terminal erythroid maturation. Induced during cell erythroid differentiation (PubMed:20427704).|||Catalyzes the export of an unknown physiological substrate from the mitochondrial matrix to the cytosol in an ATP-dependent manner (PubMed:26053025). May also transport the heme analog Zn (II) mesoporphyrin (ZnMP) in an ATP dependent manner but can't export the heme precursor 5-aminolevulinic acid (ALA) from mitochondria (PubMed:28808058, PubMed:26053025). Plays a role in the early step of the heme biosynthetic process during insertion of iron into protoporphyrin IX (PPIX). In turn participates in hemoglobin synthesis and also protects against oxidative stress (PubMed:22240895, PubMed:28808058, PubMed:24421385). In addition may be involved in mitochondrial unfolded protein response (UPRmt) signaling pathway, although ABCB10 probably does not participate in peptide export from mitochondria (By similarity).|||Expressed at particularly high levels in fetal liver, and erythroid tissues of embryos and adults. Found also in adult bone marrow, liver and kidney, and at lower levels in heart, brain and spleen.|||Homodimer or homooligomer (PubMed:15215243, PubMed:30765471). Interacts with PAAT (By similarity). Interacts with SLC25A37; this interaction stabilizes SLC25A37 and enhances the function of SLC25A37 to import mitochondrial iron during erythroid differentiation (PubMed:19805291). Interacts with FECH; this interaction may allow the formation of an oligomeric complex with SLC25A37 (PubMed:20427704). Forms a complex with ABCB7 and FECH, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). Interacts with FECH (By similarity).|||Homozygous knockout mice for ABCB10 are embryonic lethal and embryos are pale and die between 10.5 and 11.5 dpc because of embryonic hematopoietic failure (PubMed:24421385, PubMed:22240895). Embryos are completely resorbed by the uterus by 13.5 dpc and present severe anemia at 10.5 dpc (PubMed:22240895).|||Mitochondrion inner membrane|||Oxidized glutathione (GSSG) stimulates ATP hydrolysis without affecting ATP binding, whereas reduced glutathione (GSH) inhibits ATP binding and hydrolysis. http://togogenome.org/gene/10090:Rpl3 ^@ http://purl.uniprot.org/uniprot/P27659 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL3 family.|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with DHX33 (PubMed:26100019).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Constitutively monomethylated at His-245 by METTL18. Methylation at His-245 regulates translation elongation by slowing ribosome traversal on tyrosine codons: slower elongation provides enough time for proper folding of synthesized proteins and prevents cellular aggregation of tyrosine-rich proteins. It is not required for incorporation of RPL3 into ribosomes.|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Or5g25 ^@ http://purl.uniprot.org/uniprot/Q8VFK2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Gc ^@ http://purl.uniprot.org/uniprot/P21614 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with membrane-bound immunoglobulin on the surface of B-lymphocytes and with IgG Fc receptor on the membranes of T-lymphocytes (By similarity). Interacts with LRP2; the interaction is required for renal uptake of GC in complex with 25-hydroxyvitamin D3 (PubMed:10052453).|||Belongs to the ALB/AFP/VDB family.|||Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation.|||Secreted http://togogenome.org/gene/10090:Arhgap28 ^@ http://purl.uniprot.org/uniprot/Q8BN58 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Stx4a ^@ http://purl.uniprot.org/uniprot/P70452 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Cell membrane|||Interacts with STXBP6. Component of the SNARE complex composed of STX4, SNAP23 and VAMP7 that interacts with SYT7 during lysosomal exocytosis (By similarity). Found in a complex with VAMP8 and SNAP23. Detected in a complex with SNAP23 and STXBP4. Interacts with VAMP2. Interacts with SNAP23 and SNAPIN. Interacts with LLGL1. Interacts (via C-terminus) with CENPF. Interacts with DOC2B. Interacts with STXBP3; excludes interaction with DOC2B and SNAP25. Interacts with STXBP4; excludes interaction with VAMP2. Interacts with STXBP5L.|||Plasma membrane t-SNARE that mediates docking of transport vesicles. Necessary for the translocation of SLC2A4 from intracellular vesicles to the plasma membrane. In neurons, recruited at neurite tips to membrane domains rich in the phospholipid 1-oleoyl-2-palmitoyl-PC (OPPC) which promotes neurite tip surface expression of the dopamine transporter SLC6A3/DAT by facilitating fusion of SLC6A3-containing transport vesicles with the plasma membrane (By similarity). Together with STXB3 and VAMP2, may also play a role in docking/fusion of intracellular GLUT4-containing vesicles with the cell surface in adipocytes and in docking of synaptic vesicles at presynaptic active zones.|||neuron projection http://togogenome.org/gene/10090:Ran ^@ http://purl.uniprot.org/uniprot/P62827 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation by KAT5 at Lys-134 is increased during mitosis, impairs RANGRF binding and enhances RCC1 binding. Acetylation at Lys-37 enhances the association with nuclear export components. Deacetylation of Lys-37 by SIRT7 regulates the nuclear export of NF-kappa-B subunit RELA/p65.|||Belongs to the small GTPase superfamily. Ran family.|||Cytoplasm|||Expressed in a variety of tissues, including testis.|||GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs. Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis. Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport. Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation. Required for normal progress through mitosis. The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2. Enhances AR-mediated transactivation.|||Melanosome|||Mg(2+) interacts primarily with the phosphate groups of the bound guanine nucleotide.|||Monomer. Interacts with RANGAP1, which promotes RAN-mediated GTP hydrolysis. Interacts with KPNB1. Interaction with KPNB1 inhibits RANGAP1-mediated stimulation of GTPase activity. Interacts with RCC1 which promotes the exchange of RAN-bound GDP by GTP. Interaction with KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP. Interacts (GTP-bound form) with TNPO1; the interaction is direct. Interacts (GTP-bound form) with TNPO3; the interaction is direct. Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity (By similarity). Interacts (via C-terminus) with RANBP1, which alleviates the inhibition of RAN GTPase activity (PubMed:7891706, PubMed:9428644). Interacts with RANGRF, which promotes the release of bound guanine nucleotide (PubMed:10811801). RANGRF and RCC1 compete for an overlapping binding site on RAN. Identified in a complex with KPNA2 and CSE1L; interaction with RANBP1 mediates dissociation of RAN from this complex. Interaction with both RANBP1 and KPNA2 promotes dissociation of the complex between RAN and KPNB1. Identified in a complex composed of RAN, RANGAP1 and RANBP1. Identified in a complex that contains TNPO1, RAN and RANBP1. Identified in a nuclear export complex with XPO1. Found in a nuclear export complex with RANBP3 and XPO1. Interacts with RANBP2/NUP358. Interaction with RANBP1 or RANBP2 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1 (By similarity). Found in a nuclear export complex with RAN, XPO5 and pre-miRNA (By similarity). Interacts (GTP-bound form) with XPO5 (By similarity). Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5 (By similarity). Interacts with RANBP9 and RANBP10 (PubMed:18347012). Interacts in its GTP-bound form with BIRC5/survivin at S and M phases of the cell cycle. Interacts with TERT; the interaction requires hydrogen peroxide-mediated phosphorylation of TERT and transports TERT to the nucleus. Interacts with MAD2L2. Interacts with VRK1 and VRK3. Interacts with VRK2 (By similarity). Interacts with NEMP1 and KPNB1 (PubMed:25946333). Interacts (GDP-bound form) with NUTF2; regulates RAN nuclear import. Interacts with CAPG; mediates CAPG nuclear import. Interacts with NUP153. Interacts with the AR N-terminal poly-Gln region; the interaction with AR is inversely correlated with the poly-Gln length (By similarity). Interacts with MYCBP2, which promotes RAN-mediated GTP hydrolysis (PubMed:26304119). Interacts with EPG5 (By similarity).|||Nucleus|||Nucleus envelope|||cytosol http://togogenome.org/gene/10090:Sar1a ^@ http://purl.uniprot.org/uniprot/Q99JZ4 ^@ Similarity ^@ Belongs to the small GTPase superfamily. SAR1 family. http://togogenome.org/gene/10090:Castor2 ^@ http://purl.uniprot.org/uniprot/Q8CAB8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GATS family.|||Forms homodimers and heterodimers with CASTOR1. Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is not regulated by arginine.|||Functions as a negative regulator of the TORC1 signaling pathway through the GATOR complex. As part of homodimers or heterodimers with CASTOR1, directly binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1. Does not directly bind arginine, but binding of arginine to CASTOR1 disrupts the interaction of CASTOR2-containing heterodimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway.|||cytosol http://togogenome.org/gene/10090:Pla2g10 ^@ http://purl.uniprot.org/uniprot/Q8C5Y6|||http://purl.uniprot.org/uniprot/Q8K130|||http://purl.uniprot.org/uniprot/Q9QXX3 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||During hair follicle growth cycle, it is detected at low levels at 17.5 dpc (hair folliculogenesis stage), increases to a maximum expression level by P10 (anagen), declines to the basal level at P15-20 (catagen to telogen), and again increases at P25 (re-entry into the next anagen).|||Expressed at high levels in testis and the gastrointestinal tract including stomach and colon. Expressed at lower levels in other tissues including small intestine, uterus, oviduct, lung, thymus, spleen and brain (PubMed:11019817, PubMed:21266581). Expressed in Paneth-like secretory epithelial cells of the colon (PubMed:27292189). Expressed in gastric and ileac epithelial cells and in glandular epithelium of intestinal mucosa (at protein level) (PubMed:21266581). Expressed in late spermatogenic cells, spermatocytes and spermatids, but not spermatogonia in seminiferous tubules (at protein level) (PubMed:20424324). Expressed mainly in the apical side of endometrial epithelial cells and in the interstitium beneath the epithelium of uterus (at protein level) (PubMed:21266581). Expressed in resident spleen macrophages (at protein level) (PubMed:11019817). Expressed at outermost layer of hair follicles (PubMed:21266583). Expressed in dorsal root ganglia in both NEFH-positive A-fibers and PRPH-positive C-fibers (at protein level) (PubMed:21266581).|||Interacts with PLA2R1; this interaction mediates PLA2G10 clearance and inactivation.|||Lysosome|||Mutant male mice have reduced fertility due to deficient acrosome reaction (PubMed:20424324). Mutant mice are lean and protected from age-related adiposity and fatty liver (PubMed:21266581). Mutant mice show resistance to allergen-induced asthma, with marked reduction of inflammatory cell recruitment in the lungs, reduced goblet cell metaplasia, smooth muscle cell layer thickening and subepithelial fibrosis and impaired mucus hypersecretion. This resistance to allergen-induced inflammation is associated with deficient T helper type 2 immune response and decreased eicosanoid synthesis (PubMed:17403936). Mutant mice are protected against airway allergic inflammation induced by house dust mite allergens (PubMed:29093264). Mutant mice show hair shaft abnormalities including hypoplastic outer root sheath and reduced number of melanin granules (PubMed:21266583).|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with preference for phosphatidylcholines and phosphatidylglycerols over phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty acyls (PubMed:12359733, PubMed:10531313). Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (By similarity). Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells (By similarity). Efficiently hydrolyzes and inactivates PAF, a potent lipid mediator present in oxidized LDL (By similarity). May act in an autocrine and paracrine manner. Secreted by lung epithelium, targets membrane phospholipids of infiltrating eosinophils, releasing arachidonate and boosting eicosanoid and cysteinyl leukotriene synthesis involved in airway inflammatory response (PubMed:29093264, PubMed:17403936). Secreted by gut epithelium, hydrolyzes dietary and biliary phosphatidylcholines in the gastrointestinal lumen, thereby regulating adipogenesis and body weight (PubMed:21266581). Plays a stem cell regulator role in colon epithelium. Within intracellular compartment, mediates Paneth-like cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates the Wnt signaling pathway in ISCs and tissue regeneration (PubMed:27292189). May participate in hair follicle morphogenesis by regulating phosphatidylethanolamines metabolism at the outermost epithelial layer and facilitating melanin synthesis (PubMed:21266583). By generating lysophosphatidylcholines (LPCs) at sperm acrosome controls sperm cell capacitation, acrosome reaction and overall fertility (PubMed:20424324, PubMed:21266581). May promote neurite outgrowth in neuron fibers involved in nociception (PubMed:21266581). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria (PubMed:12359733). Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541). In pulmonary epithelium, may contribute to host defense response against adenoviral infection. Prevents adenovirus entry into host cells by hydrolyzing host cell plasma membrane, releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and viral infection. Likely prevents adenoviral entry into the endosomes of host cells (By similarity). May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells (PubMed:29093264).|||Up-regulated in alveolar macrophages upon allergen-induced airway inflammation (PubMed:17403936). Up-regulated in bronchoalveolar lavage fluid (BALF) in response to house dust mite proteolytic allergens (PubMed:29093264).|||acrosome http://togogenome.org/gene/10090:Gm21573 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or4c1 ^@ http://purl.uniprot.org/uniprot/Q7TQZ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4a79 ^@ http://purl.uniprot.org/uniprot/Q7TQZ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hacd3 ^@ http://purl.uniprot.org/uniprot/Q8K2C9 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the very long-chain fatty acids dehydratase HACD family.|||Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Involved in Rac1-signaling pathways leading to the modulation of gene expression. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (By similarity).|||Endoplasmic reticulum membrane|||May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex. Interacts with RAC1. Associates with internalized insulin receptor/INSR complexes on Golgi/endosomal membranes; HACD3/PTPLAD1 together with ATIC and PRKAA2/AMPK2 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (By similarity).|||Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity. http://togogenome.org/gene/10090:Tmem221 ^@ http://purl.uniprot.org/uniprot/Q8K071 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pigs ^@ http://purl.uniprot.org/uniprot/Q3V307|||http://purl.uniprot.org/uniprot/Q6PD26 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGS family.|||Component of the GPI transamidase complex. Essential for transfer of GPI to proteins, particularly for formation of carbonyl intermediates (By similarity).|||Endoplasmic reticulum membrane|||Forms a complex with PIGK/GPI8, PIGT, PIGU and GAA1.|||Membrane http://togogenome.org/gene/10090:Dlg3 ^@ http://purl.uniprot.org/uniprot/P70175 ^@ Function|||Similarity|||Subunit ^@ Belongs to the MAGUK family.|||Interacts through its PDZ domains with NETO1, GRIN2B, SYNGAP1 and APC. Interacts through its first two PDZ domains with ERBB4. Interacts through its third PDZ domain with NLGN1, and probably with NLGN2 and NLGN3. Interacts through its guanylate kinase-like domain with DLGAP1, DLGAP2, DLGAP3 and DLGAP4 (By similarity). Interacts with FRMPD4 (via C-terminus) (By similarity). Interacts with LRFN1, LRFN2 and LRFN4 (By similarity). Interacts with FLTP. Interacts with GPR85 (PubMed:25780553). Interacts with DGKI (via PDZ-binding motif) (PubMed:21119615).|||Required for learning most likely through its role in synaptic plasticity following NMDA receptor signaling. http://togogenome.org/gene/10090:Arhgap32 ^@ http://purl.uniprot.org/uniprot/Q811P8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PX domain-containing GAP family.|||Endoplasmic reticulum membrane|||Endosome membrane|||GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity.|||Golgi apparatus membrane|||Interacts with NTRK1 (via cytoplasmic domain); the interaction is independent of the phosphorylation state of NTRK1 (By similarity). Interacts with SHC3 (via SH2 domain) (By similarity). Interacts with RASA1 (via SH3 domain); the interaction is necessary for the Ras activation and cell transforming activities of ARHGAP32. Interacts with GAB1 and GAB2. Interacts with CRK and CRKL. Found in a complex with CRKL and BCAR1; upon EGF stimulation BCAR1 may be replaced by EGFR (By similarity). Interacts with NCK1 (via SH3 domain); NCK1 recruits phosphorylated BCAR1 to the complex. Isoform 2 interacts with FYN; the interaction appears to be dependent on tyrosine phosphorylation of ARHGAP32 (By similarity). Interacts with EGFR; the interaction requires EGF stimulation and is increased by SHC3. Interacts with CDC42; the interaction requires constitutively active CDC42. Interacts with CTNNB1, DLG4, CDH2 and GRIN2B (By similarity) (PubMed:12531901, PubMed:12857875, PubMed:16716191, PubMed:17272280, PubMed:17663722). Interacts with GPHN (PubMed:27609886).|||Isoform 1 and isoform 2 are highly expressed in brain, specially in cortex, corpus striatum, hippocampus and thalamus. Low levels in cerebellum, colon, small intestine, and kidney.|||Isoform 1 is detectable by embryonic day 13, whereas isoform 2 is detected postnatally.|||Isoform 2 is phosphorylated on multiple tyrosine residues by FYN (By similarity). Phosphorylated tyrosine residues undergo dephosphorylation after stimulation of NMDA receptors. Phosphorylated in vitro by CaMK2 in the presence of calmodulin and calcium; which inhibits GAP activity.|||Membrane|||Mice are fertile but display abnormal neurite growth.|||Postsynaptic density|||The N-terminal PX domain interacts specifically with phosphatidylinositides.|||cell cortex|||dendritic spine http://togogenome.org/gene/10090:Cnot9 ^@ http://purl.uniprot.org/uniprot/Q9JKY0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CNOT9 family.|||Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation. Required for retinoic acid-induced differentiation of F9 teratocarcinoma cells. Does not bind DNA by itself. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors. May play a role in cell differentiation.|||Detected at low levels in bone marrow and thymus.|||Homodimer. Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. Interacts with MYB, ATF2, RARA, RARB, RARG, RXRA, RXRB and RXRG. Identified in a complex with ATF2 bound to target DNA. Interacts with NANOS2. Directly interacts with ZNF335 (By similarity).|||Nucleus|||P-body|||Up-regulated by EPO and EGF. Transiently up-regulated by retinoic acid in F9 teratocarcinoma cells. http://togogenome.org/gene/10090:Ptf1a ^@ http://purl.uniprot.org/uniprot/Q9QX98 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the pancreas transcription factor 1 complex (PTF1) which is composed of TCF3/p75, TCF12/p64 and PTF1A/p48. TCF3 is responsible for the nuclear import of the p48/p64 complex. Interacts with TCF3 and RBPSUH/RBP-Jkappa.|||Cytoplasm|||Early postnatal lethal phenotype characterized by a lack of the exocrine pancreas, however, islet-like endocrine cell clusters are formed. A redirection of pancreatic precursors to intestinal fates is seen. At 16.5 dpc embryos show reduced size of cerebellar primordium and cerebellar aplasia.|||Expressed at an early stage of pancreas development, shortly after the onset of endodermal budding that forms the pancreatic anlage. In 9.5 dpc embryo, expression is in the myelencephalon and the neural tube at the cervical level. In the 10.5 dpc embryo expression expands as a thin stripe to the posterior end of the neural tube. The central nervous system anterior to the myelencephalon is devoid of expression at this stage. In 12-12.5 dpc embryo, expression expands anteriorly to the cerebellum region. During retinogenesis, restricted to postmitotic neuronal precursor population in the ventricular zone of the developing retina. Not expressed before 12.5 dpc when is detected in the central region of the retina. By 14.5, expands from the center to the entire retina. Between 16.5 dpc and P1, continues to be expressed strongly in a subset of cells within the outer neuroblastic layer. Expression begins to be down-regulated by P2 and is undetectable in retinas from P6.|||Expressed in precursors of pancreatic islets, acini and ducts.|||Nucleus|||Transcription factor implicated in the cell fate determination in various organs. Binds to the E-box consensus sequence 5'-CANNTG-3'. Plays a role in early and late pancreas development and differentiation. Important for determining whether cells allocated to the pancreatic buds continue towards pancreatic organogenesis or revert back to duodenal fates. May be involved in the maintenance of exocrine pancreas-specific gene expression including ELA1 and amylase. Required for the formation of pancreatic acinar and ductal cells. Plays an important role in cerebellar development. Directly regulated by FOXN4 and RORC during retinal development, FOXN4-PTF1A pathway plays a central role in directing the differentiation of retinal progenitors towards horizontal and amacrine fates. http://togogenome.org/gene/10090:Nfib ^@ http://purl.uniprot.org/uniprot/P97863|||http://purl.uniprot.org/uniprot/Q6GSP7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CTF/NF-I family.|||Binds DNA as a homodimer.|||Highest expression in lung, skeletal muscle and heart. Lower levels in liver, kidney and brain. Very low levels in testis and spleen.|||NFIB knockout results in failure of lung maturation, and severe defects in development of the corpus callosum, specific midline glial populations, the hippocampus and the pons. GFAP expression is reduced in brains of NFIB-null mice (PubMed:15632069). Conditional NFIB knockdown in the telencephalon results in significant enlargement of the cerebral cortex with preservation of overall brain structure and inter-hemispheric connectivity (PubMed:30388402).|||Nucleus|||Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional activator of GFAP, essential for proper brain development (PubMed:15632069, PubMed:30388402). Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication (PubMed:30388402). http://togogenome.org/gene/10090:Or8c8 ^@ http://purl.uniprot.org/uniprot/F8VQN7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam89b ^@ http://purl.uniprot.org/uniprot/Q9QUI1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with mouse mammary tumor virus (MMTV) envelope glycoprotein gp70.|||(Microbial infection) May be a receptor for mouse mammary tumor virus (MMTV).|||Belongs to the FAM89 family.|||Cell surface|||Cytoplasm|||Expressed in forebrain at 16 dpc.|||Interacts with SKI (PubMed:12646588). Interacts (via LRR repeat) with CDC42BPA (via AGC-kinase C-terminal domain), CDC42BPB (via AGC-kinase C-terminal domain) and LIMK1 (via LIM zinc-binding domains). Forms a tripartite complex with CDC42BPA, CDC42BPB and LIMK1 (PubMed:25107909).|||Negatively regulates TGF-beta-induced signaling; in cooperation with SKI prevents the translocation of SMAD2 from the nucleus to the cytoplasm in response to TGF-beta (PubMed:12646588). Acts as an adapter that mediates the specific recognition of LIMK1 by CDC42BPA and CDC42BPB in the lamellipodia. LRAP25-mediated CDC42BPA/CDC42BPB targeting to LIMK1 and the lamellipodium results in LIMK1 activation and the subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (PubMed:25107909).|||Widely expressed. Expressed in the early postnatal brain.|||lamellipodium http://togogenome.org/gene/10090:Mdfic ^@ http://purl.uniprot.org/uniprot/Q8BX65 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MDFI family.|||Cell membrane|||Cytoplasm|||In the embryo, robust expression is detected between 16.5 and 18.5 dpc in lung, kidney, and salivary glands. In the developing cardiovascular system, it is detected in lymphatic and cardiac valves (at protein level).|||Interacts with HAND1; leading to sequester HAND1 into the nucleolus and prevent its activity (PubMed:17891141). The C-terminus interacts with ZIC2 (PubMed:15207726, PubMed:15465018). The C-terminus interacts with AXIN1, the histidine-rich region of CCNT1/cyclin-T and weakly with LEF1. Interacts with CCNT2 (By similarity). Interacts with GATA2 (PubMed:35235341).|||Required to control the activity of various transcription factors through their sequestration in the cytoplasm. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the cytoplasm and inhibits their transcriptional activation. Modulates the expression from cellular promoters. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin-regulation of the WNT and JNK signaling pathways. Involved in the development of lymphatic vessel valves (PubMed:35235341). It is required to promote lymphatic endothelial cell migration, in a process that involves down-regulation of integrin beta 1 activation and control of cell adhesion to the extracellular matrix (By similarity).|||Secreted|||The cysteine-rich C-terminus is involved in its granular distribution in the cytoplasm (By similarity). The cysteine-rich C-terminus mediates protein-protein interactions, including interaction with HIV-1 Tat, transcription factors, AXIN1, CCNT1 (By similarity). http://togogenome.org/gene/10090:Ero1a ^@ http://purl.uniprot.org/uniprot/Q4FK57|||http://purl.uniprot.org/uniprot/Q8R180 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EROs family.|||Endoplasmic reticulum membrane|||Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-94 and Cys-130, and between Cys-99 and Cys-104. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity).|||Golgi apparatus lumen|||N-glycosylated.|||Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. Required for the proper folding of immunoglobulins (By similarity). Plays an important role in ER stress-induced, CHOP-dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1.|||Phosphorylated on Ser-144 by FAM20C in the Golgi which increases its enzymatic activity (By similarity). Phosphorylation is induced by lactation (PubMed:29858230). It is also induced by hypoxia and reductive stress (By similarity).|||Predominantly monomer. May function both as a monomer and a homodimer. Interacts with PDILT. Interacts with ERP44; the interaction results in retention of ERO1A in the endoplasmic reticulum.|||Secreted|||Stimulated by hypoxia; suggesting that it is regulated via the HIF-pathway. By ER stress in a DDIT3/CHOP-dependent manner.|||The Cys-94/Cys-99 and Cys-390/Cys-393 disulfide bonds constitute the redox-active center. The Cys-94/Cys-99 disulfide bond may accept electron from P4HB and funnel them to the active site disulfide Cys-390/Cys-393. The regulatory Cys-99/Cys-104 disulfide bond stabilizes the other regulatory bond Cys-94/Cys-130 (By similarity).|||Widely expressed (at protein level) (PubMed:20308425). In the mammary gland, expressed at higher levels in lactating mice than in virgin mice (at protein level) (PubMed:29858230).|||dendrite http://togogenome.org/gene/10090:Snn ^@ http://purl.uniprot.org/uniprot/P61807 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the stannin family.|||Mitochondrion outer membrane|||Monomer.|||Plays a role in the toxic effects of organotins (By similarity). Plays a role in endosomal maturation (PubMed:27015288). http://togogenome.org/gene/10090:Vmn1r131 ^@ http://purl.uniprot.org/uniprot/D3YTY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptpn2 ^@ http://purl.uniprot.org/uniprot/Q06180 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1 (via cytoplasmic domain); activates the phosphatase activity towards EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-mediated signaling. Interacts with MET (By similarity).|||Newborn mice are viable and do not display physical abnormalities. However, by 3 to 5 weeks of age they develop hunched posture, diarrhea and anemia. They do not survive beyond 5 weeks of age due to severe anemia, hematopoietic defects and the development of progressive systemic inflammatory disease. They display splenomegaly, lymphadenopathy and thymic atrophy, associated with altered B-cell differentiation, altered erythropoiesis, and impaired T- and B-cell functions. The inflammatory disease is characterized by high levels of circulating pro-inflammatory cytokines and lymphocytic infiltrates in non-lymphoid tissues. Heterozygous Ptpn2+/- mice exhibit decreased gluconeogenesis and hepatic glucose production while muscle-specific disruption of Ptpn2 has no effect on insulin signaling and glucose homeostasis in this tissue.|||Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Also plays an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. May also bind DNA.|||Nucleus|||Specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated through phosphorylation by PKR.|||Ubiquitously expressed. The highest expression levels were found in ovary, testis, thymus and kidney.|||Was reported to dephosphorylate STAT5A and STAT5B in the nucleus to negatively regulate prolactin-mediated signaling pathway (PubMed:11773439). However, the corresponding article has been retracted (PubMed:24319783). http://togogenome.org/gene/10090:Plaa ^@ http://purl.uniprot.org/uniprot/P27612 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At stage 11.5 dpc ubiquitously expressed (PubMed:28413018).|||Belongs to the WD repeat PLAP family.|||Cytoplasm|||Expressed in the brain, with highest levels in hippocampal neurons, cerebellar granular cell layer and Purkinje cells (PubMed:28413018).|||In smooth muscle and endothelial cells by leukotriene D4, by tumor necrosis factor in endothelial cells and by uric acid crystals in macrophages.|||Interacts with ubiquitin. Interacts with UBXN6, VCP and YOD1; may form a complex involved in macroautophagy.|||Mice die perinatally and exhibit spleen, lung and brain developmental anomalies (PubMed:28413018, PubMed:28007986). Display less matured and differentiated embryonic cortical neurons (PubMed:28007986). Display reduced ubiquitin-dependent membrane protein trafficking from early to late endosomes (PubMed:28413018). Show reduced prostaglandin E2 biosynthesis in embryonic brain, lung and heart, but not in liver at 18 dpc (PubMed:28007986).|||Nucleus|||Plays a role in protein ubiquitination, sorting and degradation through its association with VCP (By similarity). Involved in ubiquitin-mediated membrane proteins trafficking to late endosomes in an ESCRT-dependent manner, and hence plays a role in synaptic vesicle recycling (PubMed:28413018). May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes (By similarity). Plays a role in cerebellar Purkinje cell development (PubMed:28413018). Positively regulates cytosolic and calcium-independent phospholipase A2 activities in a tumor necrosis factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and hence prostaglandin E2 biosynthesis (PubMed:28007986).|||Several frameshifts and contaminating sequence.|||Synapse|||The PFU domain mediates interaction with ubiquitin.|||The PUL domain is composed of 6 armadillo-like repeats and mediates the interaction with VCP C-terminus. http://togogenome.org/gene/10090:E2f2 ^@ http://purl.uniprot.org/uniprot/P56931 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E2F/DP family.|||Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F2 complex binds specifically hypophosphorylated retinoblastoma protein RB1. During the cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB protein, thus releasing the active complex. Binds EAPP.|||Expressed in the developing epidermis and intestinal epithelium. First detected in the epidermis at stage 13.5-14.5 dpc with higher levels in the head and thorax regions. At 15.5 dpc, expression is found in both the epithelium and, to a lesser extent in the underlying mesenchyme. At day 16.5 dpc, high expression in the basal cells. Later expression is found in the developing hair follicles, around the dermal papillae. In the developing intestinal epithelium, expression first observed around 14.5 dpc. Levels continue to increase at least until 19.5 dpc, with highest levels in the intervillus epithelium and in the bottom half of the villi. In the nervous system, first expressed at 9.5 dpc, in the forebrain. At 10.5 dpc, expressed broadly in the brain, and at lower levels in the upper regions of the spinal cord. By 11.5 dpc, E2F2 expression is found throughout the central nervous system and levels peak at 12.5-15.5 dpc. In the developing spinal cord, E2F2 expression found only in the dorsal region. In the developing retina, highest expression found in the 14.5-18.5 dpc embryonic retinoblastic cell layer. In other developing tissues, E2F2 is found highest in thymus and liver, with lower expression in lung, heart, kidney and skeletal muscle. Also found in choroid plexus and chondrocytes.|||Nucleus|||Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase.|||Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from g1 to s phase. E2F2 binds specifically to RB1 in a cell-cycle dependent manner. http://togogenome.org/gene/10090:Myo7b ^@ http://purl.uniprot.org/uniprot/Q99MZ6 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Detected in intestinal enterocytes at embryonic day 17.|||Expressed primarily in kidney and intestine. Detected in proximal tubule cells of the kidney and enterocytes of the intestine, specifically the distal tips of apical microvilli on these transporting epithelial cells (at protein level).|||Myosins are actin-based motor molecules with ATPase activity. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length. May link the complex to the actin core bundle of microvilli.|||Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5. Interacts with CDHR2. Interacts with CDHR5. Interacts with USH1C (By similarity). Interacts with ANKS4B; requires initial interaction with USH1C (Probable).|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-7 (MYH7).|||cytoskeleton|||microvillus http://togogenome.org/gene/10090:Il4ra ^@ http://purl.uniprot.org/uniprot/P16382|||http://purl.uniprot.org/uniprot/Q3U905 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||Binds IL-4.|||Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Expressed in both Th1 and Th2 cells.|||Lacks the cytoplasmic domain. Binds IL4.|||On IL4 binding, phosphorylated on C-terminal tyrosine residues.|||Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.|||Secreted|||Soluble IL4R can also be produced by proteolytic cleavage at the cell surface (shedding).|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||The extracellular domain represents the IL4 binding protein (IL4BP).|||The functional IL4 receptor is formed by initial binding of IL4 to IL4R. Subsequent recruitment to the complex of the common gamma chain, in immune cells, creates a type I receptor and, in non-immune cells, of IL13RA1 forms a type II receptor. IL4R can also interact with the IL13/IL13RA1 complex to form a similar type II receptor. Interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP. Interacts with JAK3 (By similarity). Interacts with PIK3C3 (PubMed:8390454). Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5 (PubMed:12242343). Interacts with SOCS5; inhibits IL4 signaling (PubMed:12242343). Interacts with CLM1 (PubMed:26124135).|||The sequences from strains C3H, CBA, DBA/2 and FVB/N are all identical to the one displayed. http://togogenome.org/gene/10090:Or13a1 ^@ http://purl.uniprot.org/uniprot/Q8VGH2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lypd3 ^@ http://purl.uniprot.org/uniprot/Q91YK8 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Binds laminin-1 and laminin-5. Interacts with LGALS3. Interacts with AGR2 and AGR3 (By similarity).|||Cell membrane|||Supports cell migration. May be involved in tumor progression (By similarity).|||Up-regulated in suprabasal keratinocytes of hyperplastic skin induced by phorbol-ester. http://togogenome.org/gene/10090:Ythdc2 ^@ http://purl.uniprot.org/uniprot/B2RR83 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Ketu' is a harbinger of misfortune in Vedic mythology (PubMed:29360036).|||3'-5' RNA helicase that plays a key role in the male and female germline by promoting transition from mitotic to meiotic divisions in stem cells (PubMed:28380054, PubMed:28809393, PubMed:29033321, PubMed:29087293, PubMed:29360036, PubMed:32470506). Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs that plays a role in the efficiency of RNA processing and stability (PubMed:29360036). Essential for ensuring a successful progression of the meiotic program in the germline by regulating the level of m6A-containing RNAs (PubMed:29033321). Acts by binding and promoting degradation of m6A-containing mRNAs: the 3'-5' RNA helicase activity is required for this process and RNA degradation may be mediated by XRN1 exoribonuclease (PubMed:29033321). Required for both spermatogenesis and oogenesis (PubMed:28809393, PubMed:29033321).|||Belongs to the DEAD box helicase family. DEAH subfamily.|||Cytoplasm|||Expression rises between 7 and 12 d.p.p. and remains steady through adulthood.|||Interacts with MEIOC; binds transcripts that regulate the mitotic cell cycle inhibiting progression into metaphase, thereby allowing meiotic prophase to proceed normally (PubMed:28380054, PubMed:29087293). Interacts (via ANK repeats) with XRN1 (By similarity). Interacts with ZCCHC4 (By similarity). Associates with the small ribosomal subunit (By similarity). Interacts with RBM46 (PubMed:36001654).|||Mice are viable and reach adulthood (PubMed:28809393, PubMed:29087293, PubMed:29033321). However, both male and female mice are infertile; male mice have smaller testes, and female mice have smaller ovaries and show progressive loss of germ cells (PubMed:28809393, PubMed:29087293, PubMed:29033321). Mutant germ cells enter meiosis but proceed prematurely to aberrant metaphase and apoptosis, and display defects in transitioning from spermatogonial to meiotic gene expression programs (PubMed:29087293, PubMed:29033321). Mutant testes reveal an up-regulation of N6-methyladenosine (m6A)-enriched transcripts (PubMed:29033321).|||Present in male and female germ cells (at protein level) (PubMed:29033321, PubMed:32470506). Highly expressed in testis (PubMed:28809393, PubMed:29033321, PubMed:29087293, PubMed:29360036). Not detected in spermatogonia next to the tubule wall but is strongly expressed in spermatocytes, suggesting that it is up-regulated in germ cells upon entry into meiosis (at protein level) (PubMed:29087293).|||The YTH domain mediates RNA-binding. It recognizes and binds N6-methyladenosine (m6A)-containing RNAs.|||perinuclear region http://togogenome.org/gene/10090:Ano6 ^@ http://purl.uniprot.org/uniprot/A0A2I3BPX3|||http://purl.uniprot.org/uniprot/Q6P9J9 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc, expressed in lung epithelium and mesenchyme. At 16.5 dpc, expressed in esophageal epithelium and mesenchyme. In the caudal digestive tract, detected in small intestine epithelium at 14.5 dpc. Also detected at 14.5 dpc in epithelium and mesenchyme of trachea, ovary, kidney and stomach. In the developing skeleton, expressed in developing rib perichondria at 14.5 dpc. Also expressed in the neural tube and dorsal root ganglia at 14.5 dpc. In developing skin, expression is restricted to basal layers of the epidermis at 16.5 dpc.|||Belongs to the anoctamin family.|||Cell membrane|||Contains ten transmembrane regions, not eight as predicted.|||Exhibits synergistic gating by Ca(2+) and voltage. Inhibited by some non-specific cation channel blockers such as: ruthenium red, 2-aminoethyl diphenylborinate (2APB), gadolinium and cadmium ions.|||Homodimer.|||Membrane|||Mice are viable and fertile, and display no major morphological defects. They exhibit deficiencies in Ca(2+)-dependent phospholipid scramblase activity in platelets and defects in blood coagulation (PubMed:23021219). They also show reduced skeleton size and skeletal deformities.|||Predominant expression seen in epithelial tissues. Also found in skeletal system where it is primarily expressed in osteoblasts.|||Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets, osteoblasts and fetal thymocytes. Phospholipid scrambling results in surface exposure of phosphatidylserine which in platelets is essential to trigger the clotting system whereas in osteoblasts is essential for the deposition of hydroxyapatite during bone mineralization. Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide. Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes.|||The term 'anoctamin' was coined because these channels are anion selective and are predicted to have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Tbc1d9 ^@ http://purl.uniprot.org/uniprot/Q3UYK3 ^@ Domain|||Function ^@ May act as a GTPase-activating protein for Rab family protein(s).|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site. http://togogenome.org/gene/10090:Tmem164 ^@ http://purl.uniprot.org/uniprot/Q6PHN7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM164 family.|||Membrane|||Positive regulator of ferroptosis. Selectively mediates ATG5-dependent autophagosome formation during ferroptosis, rather than during starvation, and regulates the degradation of ferritin, GPX4 and lipid droplets to increase iron accumulation and lipid peroxidation, thereby promoting ferroptotic cell death. http://togogenome.org/gene/10090:D7Ertd443e ^@ http://purl.uniprot.org/uniprot/D2J0Y4|||http://purl.uniprot.org/uniprot/G3UZF7|||http://purl.uniprot.org/uniprot/Q9D4E0 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in testis. Weak expression found in brain, lung, heart, ovary, thymus, spleen and kidney.|||Interacts with HDAC1; the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21 (PubMed:20154723). Interacts with p53/TP53; the interaction inhibits binding of p53/TP53 and MDM2 (PubMed:24240685).|||Tumor suppressor that is required to sustain G2/M checkpoint after DNA damage (PubMed:20843368, PubMed:20154723, PubMed:24240685). Acts as a p53/TP53 activator by inhibiting MDM2 binding to p53/TP53 and stimulating non-proteolytic polyubiquitination of p53/TP53. Exhibits ubiquitin ligase (E3) activity and assemble ubiquitin polymers through 'Lys-11'- (K11-), 'Lys-29'- (K29-) and 'Lys-63'- (K63)-linkages, independently of the ubiquitin-conjugating enzyme (E2). Promotes p53/TP53-dependent transcription of CDKN1A/p21, leading to robust checkpoint response (PubMed:24240685). Mediates CDKN1A/p21 protein stability in a ubiquitin-independent manner. Interacts with HDAC1 and prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21 (PubMed:20154723). May have a role in the assembly of primary cilia (By similarity).|||Upon DNA damage by agents such as ionizing radiation, UV and actinomycin D. Activated by p53/TP53.|||centrosome http://togogenome.org/gene/10090:Smr2 ^@ http://purl.uniprot.org/uniprot/O35979|||http://purl.uniprot.org/uniprot/O35985 ^@ Function|||Miscellaneous|||Subcellular Location Annotation ^@ May play a role in protection or detoxification.|||Produced by translation on another frame.|||Secreted http://togogenome.org/gene/10090:Slc13a3 ^@ http://purl.uniprot.org/uniprot/Q3UUJ6|||http://purl.uniprot.org/uniprot/Q91Y63 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.|||Cell membrane|||High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-6 carbon atoms, such as the citric acid cycle intermediates succinate and alpha-ketoglutarate (2-oxoglutarate), as well as other compounds including N-acetyl-L-aspartate (PubMed:11287335). Transports the dicarboxylate into the cell with a probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate, rendering the process electrogenic (PubMed:11287335). Can transport citrate in a Na(+)-dependent manner, recognizing the divalent form of citrate rather than the trivalent form which is normally found in blood (By similarity).|||Highly expressed in kidney, and at much lower levels in brain.|||Membrane http://togogenome.org/gene/10090:Stat4 ^@ http://purl.uniprot.org/uniprot/P42228|||http://purl.uniprot.org/uniprot/Q3V157 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-668 is required for JAK2-mediated phosphorylation and activation of STAT4.|||Belongs to the transcription factor STAT family.|||Cytoplasm|||Expression is restricted to testis, thymus, and spleen.|||Forms a homodimer or a heterodimer with a related family member (By similarity). Interacts with ARL2BP. Interacts with STAT1 (By similarity). Interacts with JUN; this complex efficiently interacts with the AP-1-related sequence of the IFN-gamma promoter (PubMed:14734615).|||Nucleus|||STAT4-deficient mice are grossly indistinguishable from wild-type mice. However, the development of T-helper 1 cells in response to either IL12 or Listeria monocytogenes is strongly impaired (PubMed:8700209). In addition, mice are acutely sensitive to methicillin-resistant Staphylococcus aureus (MRSA) infection (PubMed:34138758).|||Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response. Plays a key role in the differentiation of T-helper 1 cells and the production of interferon-gamma (PubMed:8700209). Participates also in multiple neutrophil functions including chemotaxis and production of the neutrophil extracellular traps (PubMed:34138758). After IL12 binding to its receptor IL12RB2, STAT4 interacts with the intracellular domain of IL12RB2 and becomes tyrosine phosphorylated. Phosphorylated STAT4 then homodimerizes and migrates to the nucleus where it can recognize STAT target sequences present in IL12 responsive genes. Although IL12 appears to be the predominant activating signal, STAT4 can also be phosphorylated and activated in response to IFN-gamma stimulation via JAK1 and TYK2 and in response to different interleukins including IL23, IL2 and IL35 (By similarity). Transcription activation of IFN-gamma gene is mediated by interaction with JUN that forms a complex that efficiently interacts with the AP-1-related sequence of the IFN-gamma promoter (PubMed:14734615). In response to IFN-alpha/beta signaling, acts as a transcriptional repressor and suppresses IL5 and IL13 mRNA expression during response to T-cell receptor (TCR) activation (By similarity).|||Tyrosine phosphorylated upon IL12 and IFN-alpha activation, but not by IFN-gamma in T-lymphocytes and NK cells. Serine phosphorylation is required for maximal transcriptional activity but not for DNA binding. Phosphorylation by MAP2K6 at Ser-722 is required for full transcriptional activity induced by IL12. However this serine phosphorylation is not required for cell proliferation although critical for IFN-gamma production. http://togogenome.org/gene/10090:Or13a24 ^@ http://purl.uniprot.org/uniprot/Q7TRT5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fuca2 ^@ http://purl.uniprot.org/uniprot/Q505Q3|||http://purl.uniprot.org/uniprot/Q99KR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.|||Belongs to the glycosyl hydrolase 29 family.|||Homotetramer.|||Secreted http://togogenome.org/gene/10090:Gpr75 ^@ http://purl.uniprot.org/uniprot/Q059L0|||http://purl.uniprot.org/uniprot/Q6X632 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed at 7 dpc and 11 dpc. Also detected at 17 dpc.|||G protein-coupled receptor that is activated by the chemokine CCL5/RANTES. Probably coupled to heterotrimeric Gq proteins, it stimulates inositol trisphosphate production and calcium mobilization upon activation. Together with CCL5/RANTES, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. CCL5/RANTES may also regulate insulin secretion by pancreatic islet cells through activation of this receptor.|||Highly expressed in brain and heart. Also detected in skeletal muscle, liver and kidney. Also expressed by islet cells (at protein level).|||Membrane http://togogenome.org/gene/10090:Scamp1 ^@ http://purl.uniprot.org/uniprot/Q3TD71|||http://purl.uniprot.org/uniprot/Q3TSA8|||http://purl.uniprot.org/uniprot/Q3UY11|||http://purl.uniprot.org/uniprot/Q8K021 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCAMP family.|||Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface (By similarity).|||Interacts with SYNRG, ITSN1 and SLC9A7.|||Membrane|||Recycling endosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Kdm5c ^@ http://purl.uniprot.org/uniprot/P41230 ^@ Cofactor|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JARID1 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Both the JmjC domain and the JmjN domain are required for enzymatic activity.|||Escapes X-inactivation.|||Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Participates in transcriptional repression of neuronal genes by recruiting histone deacetylases and REST at neuron-restrictive silencer elements (By similarity). Represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2.|||Nucleus|||Part of two distinct complexes, one containing E2F6, and the other containing REST. Interacts with ZMYND8.|||The first PHD-type zinc finger domain recognizes and binds H3-K9Me3. http://togogenome.org/gene/10090:Ralgps1 ^@ http://purl.uniprot.org/uniprot/A2AR50 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Guanine nucleotide exchange factor for the small GTPase RALA. May be involved in cytoskeleton organization.|||Interacts with the SH3 domains of GRB2, NCK1, PLCG1 and SRC.|||The PH domain mediates binding to membranes. It is required for efficient GEF activity. http://togogenome.org/gene/10090:Phaf1 ^@ http://purl.uniprot.org/uniprot/Q922R1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PHAF1 family.|||Cytoplasm|||Interacts with BCAS3; the interaction is requrired for the association with the phagophore.|||Plays a regulatory role in autophagic activity. In complex with BCAS3, associates with the autophagosome formation site during both non-selective and selective autophagy.|||Preautophagosomal structure http://togogenome.org/gene/10090:Foxi2 ^@ http://purl.uniprot.org/uniprot/A2RTG9|||http://purl.uniprot.org/uniprot/Q3I5G5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Expressed in a subset of cells of the olfactory epithelium, in the dental epithelium, in developing whiskers and in cells lining the endolymphatic duct of the inner ear at stage 16.5 dpc. Also expressed in kidney, hair follicles, thymus and in collecting ducts from the mandibular gland as well as in a subset of epithelial cells lining the sublingual and submaxillary ducts from the salivary glands to the oral cavity at stage 18.5 dpc. Expressed in the developing brain along a neuromeric boundary between prosomeres p5 and p6 as well as in the neural layer of the retina.|||Nucleus|||Possible transcriptional activator. http://togogenome.org/gene/10090:Sh3rf1 ^@ http://purl.uniprot.org/uniprot/E9QQ33|||http://purl.uniprot.org/uniprot/Q69ZI1 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated. Ubiquitinated by SH3RF2, leading to proteasome-mediated degradation.|||Belongs to the SH3RF family.|||Expressed in the embryonic brain. Expressed strongly in the venricular zone (VZ), subventricular zone (SVZ), and lower intermediate zone (IZ) but weakly in the upper IZ and cortical plate (CP) at 14.5 dpc. At 16.5 dpc, expression increases in the IZ and CP. At 18.5 dpc, it increases significantly in the CP but decreases in the IZ, SVZ, and VZ (at protein level).|||Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination. Stimulates ubiquitination of potassium channel KCNJ1, enhancing its dynamin-dependent and clathrin-independent endocytosis (By similarity). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells (PubMed:23963642, PubMed:27084103, PubMed:9482736). Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (PubMed:22959435).|||Interacts with HERP1 (By similarity). Interacts with RAC1; in a GTP-dependent manner (PubMed:22959435, PubMed:9482736). Interacts with MAP3K10/MLK2 and MAP3K11/MLK3. Interacts with MAPK8IP; this interaction leads to the PJAC complex (POSH-JIP or SH3RF1/MAPK8IP1 apoptotic complex) with a 1:1 ratio. Interacts with SIAH1. Probably part of a signaling complex that may contain SH3RF1, MAPK8IP, DLK1, MAP2K4/MKK4, MAP2K7/MKK7, MAPK8/JNK1, MAPK9/JNK2, AKT1 and AKT2 (PubMed:12514131, PubMed:14504284, PubMed:16230351, PubMed:16571722, PubMed:23963642). Found in a complex with RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103). Found in a complex with RAC1, MAP3K11/MLK3, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642). Interacts with SH3RF2 (By similarity).|||Phosphorylated at Ser-304 by AKT1 and AKT2. When phosphorylated, it has reduced ability to bind Rac.|||The RING finger domain is required for ubiquitin ligase activity and autoubiquitination.|||Ubiquitously expressed.|||lamellipodium|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Uso1 ^@ http://purl.uniprot.org/uniprot/Q9Z1Z0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VDP/USO1/EDE1 family.|||Composed of a globular head, an elongated tail (coiled-coil) and a highly acidic C-terminal domain.|||General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. May well act as a vesicular anchor by interacting with the target membrane and holding the vesicular and target membranes in proximity.|||Golgi apparatus membrane|||Homodimer. Dimerizes by parallel association of the tails, resulting in an elongated structure with two globular head domains side by side, and a long rod-like tail structure. Interacts with MIF (By similarity).|||Phosphorylated in a cell cycle-specific manner; phosphorylated in interphase but not in mitotic cells. Dephosphorylated protein associates with the Golgi membrane; phosphorylation promostes dissociation (By similarity).|||cytosol http://togogenome.org/gene/10090:Cd28 ^@ http://purl.uniprot.org/uniprot/P31041|||http://purl.uniprot.org/uniprot/Q8CDB3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked. Interacts with DUSP14. Binds to CD80/B7-1 and CD86/B7-2/B70. Interacts with GRB2 (By similarity).|||Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation.|||Membrane http://togogenome.org/gene/10090:Meltf ^@ http://purl.uniprot.org/uniprot/Q544J8|||http://purl.uniprot.org/uniprot/Q9R0R1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the transferrin family.|||Cell membrane|||Involved in iron cellular uptake. Seems to be internalized and then recycled back to the cell membrane. Binds a single atom of iron per subunit. Could also bind zinc. http://togogenome.org/gene/10090:Rhox8 ^@ http://purl.uniprot.org/uniprot/Q6VSS7 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:H2bc3 ^@ http://purl.uniprot.org/uniprot/Q64475 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Atp1a1 ^@ http://purl.uniprot.org/uniprot/Q8VDN2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.|||Melanosome|||Phosphorylation on Tyr-10 modulates pumping activity. Phosphorylation of Ser-943 by PKA modulates the response of ATP1A1 to PKC. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity (By similarity).|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with regulatory subunit FXYD1 (PubMed:17283221). Interacts with regulatory subunit FXYD3 (PubMed:15743908). Interacts with SIK1 (By similarity). Interacts with SLC35G1 and STIM1 (By similarity). Interacts with CLN3; this interaction regulates the sodium/potassium-transporting ATPase complex localization at the plasma membrane (By similarity).|||This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.|||axon|||sarcolemma http://togogenome.org/gene/10090:Tnnt2 ^@ http://purl.uniprot.org/uniprot/P50752|||http://purl.uniprot.org/uniprot/Q3TH80|||http://purl.uniprot.org/uniprot/Q54AB6|||http://purl.uniprot.org/uniprot/Q6P3Z7 ^@ Function|||PTM|||Similarity ^@ Belongs to the troponin T family.|||Phosphorylation at Thr-216 by PRKCA induces significant reduction in myofilament calcium sensitivity and actomyosin ATPase activity.|||Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. http://togogenome.org/gene/10090:Hbb-y ^@ http://purl.uniprot.org/uniprot/P02104|||http://purl.uniprot.org/uniprot/Q9CR49 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the globin family.|||Hemoglobin epsilon chain is a beta-type chain found in early embryos.|||High expression in yolk sac blood islands, fetal liver, and embryonic erythrocytes. Very low levels in adult liver and spleen. http://togogenome.org/gene/10090:Zfp536 ^@ http://purl.uniprot.org/uniprot/Q8K083 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed predominantly in the brain, while a weak signal is also detected in the heart and testis (PubMed:19398580). Expression is abundant in neuronal cells of the cerebral cortex, hippocampus and hypothalamic area (at protein level) (PubMed:19398580).|||From 9.5 dpc to 12.5 dpc, expressed in the developing central nervous system, dorsal root ganglia, eye vesicles and limbs. At 9.5 dpc, expressed in the developing forebrain, midbrain, hindbrain neural folds and spinal cord. When the embryo developed to 10.5 dpc, expressed in the telencephalic vesicles, midbrain, hindbrain, and spinal cord and is detectable in the dorsal root ganglia region and somites. Similar expression patterns at 11.5 dpc and 12.5 dpc, with significant expression in the telencephalic vesicles, midbrain, hindbrain and spinal cord.|||Nucleus|||Transcriptional repressor that negatively regulates neuron differentiation by repressing retinoic acid-induced gene transcription (PubMed:19398580). Binds and interrupts RARA from binding to retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:19398580). Recognizes and binds 2 copies of the core DNA sequence 5'-CCCCCA-3' (By similarity). http://togogenome.org/gene/10090:Dlgap1 ^@ http://purl.uniprot.org/uniprot/A0A3B2WD59|||http://purl.uniprot.org/uniprot/D3Z508|||http://purl.uniprot.org/uniprot/D3Z6F4|||http://purl.uniprot.org/uniprot/E9QAR5|||http://purl.uniprot.org/uniprot/Q3UHD8|||http://purl.uniprot.org/uniprot/Q3UVU8|||http://purl.uniprot.org/uniprot/Q9D415 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAPAP family.|||Cell membrane|||Highest levels in the neocortex, part of the hippocampus, the granule cell layer of the cerebellum, the glomerular layer of the olfactory bulb, the inner plexiform layer of the retina, the ventral and dorsal horn of the spinal chord, the neuromuscular junction and the submandibular ganglion.|||Interacts with the guanylate kinase-like domain of DLG1, DLG2, DLG3, DLG4 and AIP1. Interacts with the PDZ domain of SHANK1, SHANK2 and SHANK3. Found in a complex with DLG4 and SHANK1, SHANK2 or SHANK3. Found in a complex with DLG4 and BEGAIN. Interacts with DYL2 and LRFN1. Interacts with MPP2 (via the SH3-Guanylate kinase-like sub-module) (By similarity).|||Part of the postsynaptic scaffold in neuronal cells.|||Postsynaptic density|||Synapse|||Ubiquitinated by TRIM3; leading to proteasomal degradation. http://togogenome.org/gene/10090:Ifi213 ^@ http://purl.uniprot.org/uniprot/D3Z5G0|||http://purl.uniprot.org/uniprot/Q3UPZ5 ^@ Similarity ^@ Belongs to the HIN-200 family. http://togogenome.org/gene/10090:Cyb5rl ^@ http://purl.uniprot.org/uniprot/B1AS42 ^@ Function|||Similarity ^@ Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction. http://togogenome.org/gene/10090:Cmtm7 ^@ http://purl.uniprot.org/uniprot/Q9ESD6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the chemokine-like factor family.|||Membrane http://togogenome.org/gene/10090:Fabp12 ^@ http://purl.uniprot.org/uniprot/Q9DAK4 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Highly expressed in adult retina and testis.|||May play a role in lipid transport. http://togogenome.org/gene/10090:Or52a5 ^@ http://purl.uniprot.org/uniprot/E9PYY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Itga11 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1F0|||http://purl.uniprot.org/uniprot/Q7TQC3|||http://purl.uniprot.org/uniprot/Q8CE84 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the integrin alpha chain family.|||Membrane http://togogenome.org/gene/10090:Dzank1 ^@ http://purl.uniprot.org/uniprot/Q8C008 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Cloning artifact.|||Interacts with NINL. Associates with DYNC1H1 and multiple dynein intermediate and light chains as well as actin-binding proteins.|||Involved in vesicle transport in photoreceptor cells.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Hemk1 ^@ http://purl.uniprot.org/uniprot/Q921L7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein N5-glutamine methyltransferase family.|||Mitochondrion|||N5-glutamine methyltransferase responsible for the methylation of the glutamine residue in the universally conserved GGQ motif of the mitochondrial translation release factor MTRF1L. http://togogenome.org/gene/10090:Vnn1 ^@ http://purl.uniprot.org/uniprot/Q9Z0K8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Amidohydrolase that hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine.|||Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.|||Cell membrane|||Detected in kidney (at protein level). Ubiquitous.|||Monomer.|||N-glycosylated.|||No visible phenotype. Mice lack detectable levels of cysteamine in liver and kidney. http://togogenome.org/gene/10090:Abhd3 ^@ http://purl.uniprot.org/uniprot/Q91ZH7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.|||Detected in embryos from 7 dpc to 17 dpc.|||Membrane|||Mice lacking Abhd3 are viable, fertile and have normal behavior.|||Phospholipase that may play a role in phospholipids remodeling. May selectively cleave myristate (C14)-containing phosphatidylcholines through its predominant phospholipase 1 activity, cleaving preferentially acyl groups in sn1 position. In parallel, may have a minor phospholipase 2 activity acting on acyl groups in position sn2. In addition to (C14)-containing phosphatidylcholines, may also act on other medium-chain-containing and oxidatively truncated phospholipids.|||Widely expressed with higher expression in liver. http://togogenome.org/gene/10090:Sec22a ^@ http://purl.uniprot.org/uniprot/B2RSR2|||http://purl.uniprot.org/uniprot/Q8BH47 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptobrevin family.|||Endoplasmic reticulum membrane|||May be involved in vesicle transport between the ER and the Golgi complex.|||Membrane http://togogenome.org/gene/10090:Iqub ^@ http://purl.uniprot.org/uniprot/Q8CDK3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anchors the radial spoke 1 (RS1) complex to the A microtubule of outer doublet microtubules in axonemes (PubMed:36417862, PubMed:36355624). The triple radial spokes (RS1, RS2 and RS3) are required to modulate beating of the sperm flagellum (PubMed:36417862, PubMed:36355624). May play a role in inhibiting signaling via MAPK1/ERK2 and MAPK3/ERK1 (PubMed:36355624). Additionally, may play a role in the functioning of cilia (PubMed:21289087). Not required for the functioning of tracheal or ependymal cilia (PubMed:36417862).|||Component of the axonemal radial spoke 1 (RS1) complex, at least composed of spoke head proteins RSPH1, RSPH3B, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB (PubMed:36417862). Does not appear to be part of radial spoke complexes 2 or 3 (RS2 or RS3) (Probable). Interacts with CALM1 (PubMed:36417862). Interacts with DNAJB13 (PubMed:36417862). Interacts with DYNLL2 (PubMed:36417862). Interacts with NME5 (PubMed:36417862). Interacts with RSPH3 (By similarity). Interacts with RSPH9 (PubMed:36417862). Interacts with ZMYND10 (By similarity). Interacts with calmodulin; the interaction occurs in conditions of low but not high calcium (By similarity).|||Expressed in the flagellum of sperm cells and cilia of tracheal epithelial cells (at protein level) (PubMed:36417862). High expression in testis, also present in brain and lung (PubMed:36417862).|||Leads to an absence of radial spoke 1 (RS1) complex from sperm axonemes (PubMed:36417862). Leads to flagellar bending defects in sperm cells, and consequently abnormal flagellar beating and asthenospermia (reduced sperm motility) (PubMed:36417862, PubMed:36355624). Male mice are infertile, no effect on female fertility (PubMed:36417862, PubMed:36355624). Elongated cilia (PubMed:21289087). Increases levels of phosphorylated MAPK1/ERK2 and MAPK3/ERK1 (PubMed:36355624).|||cilium|||flagellum axoneme http://togogenome.org/gene/10090:Ngb ^@ http://purl.uniprot.org/uniprot/Q3USR6|||http://purl.uniprot.org/uniprot/Q5ZPR7|||http://purl.uniprot.org/uniprot/Q9ER97 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A redox disulfide bond regulates the heme pocket coordination and the rate of nitrite reduction to NO.|||Belongs to the globin family.|||Cytoplasm|||Involved in oxygen transport in the brain. Hexacoordinate globin, displaying competitive binding of oxygen or the distal His residue to the iron atom. Not capable of penetrating cell membranes. The deoxygenated form exhibits nitrite reductase activity inhibiting cellular respiration via NO-binding to cytochrome c oxidase. Involved in neuroprotection during oxidative stress. May exert its anti-apoptotic activity by acting to reset the trigger level of mitochondrial cytochrome c release necessary to commit the cells to apoptosis.|||Mitochondrion|||Monomer. Homodimer and homotetramer; disulfide-linked (Probable). Interacts with 14-3-3 (By similarity).|||Perikaryon|||Phosphorylated in vitro by ERK1, ERK2 and PKA, and in vivo during hypoxia. Phosphorylation increases nitrite reductase activity (By similarity).|||Predominantly expressed in brain. http://togogenome.org/gene/10090:Sod2 ^@ http://purl.uniprot.org/uniprot/P09671|||http://purl.uniprot.org/uniprot/Q4FJX9 ^@ Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-122 decreases enzymatic activity. Deacetylated by SIRT3 upon exposure to ionizing radiations or after long fasting.|||Belongs to the iron/manganese superoxide dismutase family.|||Binds 1 Mn(2+) ion per subunit.|||Destroys radicals which are normally produced within the cells and which are toxic to biological systems.|||Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.|||Expression is regulated by KRIT1.|||Homotetramer.|||Mitochondrion matrix|||Nitrated under oxidative stress. Nitration coupled with oxidation inhibits the catalytic activity (By similarity).|||Polyubiquitinated; leading to proteasomal degradation. Deubiquitinated by USP36 which increases protein stability. http://togogenome.org/gene/10090:Nol8 ^@ http://purl.uniprot.org/uniprot/E9QKD1|||http://purl.uniprot.org/uniprot/Q3UHX0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with the GTP form of RRAGA, RRAGC and RRAGD. Interacts with NIP7. Interacts with DDX18; the interaction is RNA-dependent. Interacts with DDX47; the interaction is RNA-dependent (By similarity).|||Phosphorylated.|||Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells (By similarity).|||nucleolus http://togogenome.org/gene/10090:Abhd12 ^@ http://purl.uniprot.org/uniprot/Q99LR1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serine esterase family.|||Endoplasmic reticulum membrane|||Glycosylated.|||Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:23297193, PubMed:25580854, PubMed:30420694). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (PubMed:23297193). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:18096503). Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167).|||Mice are viable and were born at the expected Mendelian frequency (PubMed:23297193). Young mice (less than 6 months old) are mostly normal in their behavior; however, as these animals age, they develop an array of phenotypes, including defective auditory and motor behavior, with concomitant cellular pathology indicative of a neuroinflammatory response (PubMed:23297193). Mice show heightened immunological responses (PubMed:30420694). Metabolomic characterization of brain tissue show striking elevations in a series of lysophosphatidylserine (LPS) lipids that occur before the onset of neuroinflammatory and behavioral defects (PubMed:23297193). Brain tissues accumulate oxidized phosphatidylserine lipids in response to severe inflammatory stress (PubMed:30643283).|||Mitochondrion|||Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea). http://togogenome.org/gene/10090:Plgrkt ^@ http://purl.uniprot.org/uniprot/Q9D3P8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in monocytes; detected in differentiated monocytes but not in progenitor cells. Expressed in adrenal medulla and hippocampus.|||Interacts with PLAT. Interacts with PLAUR (By similarity).|||Receptor for plasminogen. Regulates urokinase plasminogen activator-dependent and stimulates tissue-type plasminogen activator-dependent cell surface plasminogen activation. Proposed to be part of a local catecholaminergic cell plasminogen activation system that regulates neuroendocrine prohormone processing. Involved in regulation of inflammatory response; regulates monocyte chemotactic migration and matrix metalloproteinase activation, such as of MMP2 and MMP9. http://togogenome.org/gene/10090:Tln1 ^@ http://purl.uniprot.org/uniprot/P26039|||http://purl.uniprot.org/uniprot/Q3UHS6|||http://purl.uniprot.org/uniprot/Q80TM2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell surface|||Consists of an N-terminal FERM domain linked via a short unstructured region to a large flexible C-terminal rod which contains 13 amphipathic helical bundles (R1-R13). The rod begins with a five-helix bundle (R1) followed by three four-helix bundles (R2-R4). These are followed by a series of eight five-helix bundles (R5-R7 and R9-R13) in which the N- and C-termini are positioned at opposite ends of the bundle, creating a linear chain. The four-helix bundle R8 does not disrupt the chain because it is inserted into a loop in the R7 five-helix bundle. The uneven distribution of four- and five-helix bundles creates two distinctly different zones: a compact N-terminal region sensitive to stretch and a linear C-terminal region that is optimal for force transmission.|||High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane.|||Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (By similarity). Interacts with THSD1; this promotes interaction with PTK2/FAK1 and VCL (By similarity). Interacts with NRAP and LAYN (By similarity). Interacts with SYNM (By similarity). Interacts with ITGB1; the interaction is prevented by competitive binding of ITGB1BP1 (By similarity). Binds with high affinity to VCL and with low affinity to integrins (PubMed:23389036, PubMed:20610383, PubMed:15642262, PubMed:15272303). Interacts with APBB1IP; this inhibits VCL binding (PubMed:23389036). Interacts with PTK2/FAK1 (PubMed:7622520). Interacts with PIP5K1C (PubMed:15623515). Interacts with F-actin (PubMed:20610383).|||cytoskeleton|||focal adhesion|||ruffle membrane http://togogenome.org/gene/10090:Utp18 ^@ http://purl.uniprot.org/uniprot/Q3U3Q3|||http://purl.uniprot.org/uniprot/Q5SSI6|||http://purl.uniprot.org/uniprot/Q8BHW1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat UTP18 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA.|||nucleolus http://togogenome.org/gene/10090:Acadsb ^@ http://purl.uniprot.org/uniprot/Q9DBL1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acyl-CoA dehydrogenase family.|||Homotetramer.|||Mitochondrion matrix|||Short and branched chain specific acyl-CoA dehydrogenase that catalyzes the removal of one hydrogen from C-2 and C-3 of the fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA. Among the different mitochondrial acyl-CoA dehydrogenases, acts specifically on short and branched chain acyl-CoA derivatives such as (S)-2-methylbutyryl-CoA as well as short straight chain acyl-CoAs such as butyryl-CoA (By similarity). Plays an important role in the metabolism of L-isoleucine by catalyzing the dehydrogenation of 2-methylbutyryl-CoA, one of the steps of the L-isoleucine catabolic pathway (By similarity). Can also act on valproyl-CoA, a metabolite of the valproic acid drug (By similarity). http://togogenome.org/gene/10090:Kcnt1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JER3|||http://purl.uniprot.org/uniprot/A2AHB7|||http://purl.uniprot.org/uniprot/A2AHB8|||http://purl.uniprot.org/uniprot/A2AHB9|||http://purl.uniprot.org/uniprot/C0KTP6|||http://purl.uniprot.org/uniprot/Q6ZPR4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa4.1/KCNT1 sub-subfamily.|||Cell membrane|||Interacts (via C-terminus) with FMR1; this interaction alters gating properties of KCNT1 (By similarity). Interacts with CRBN via its cytoplasmic C-terminus (By similarity).|||Membrane|||Outwardly rectifying potassium channel subunit that may coassemble with other Slo-type channel subunits. Activated by high intracellular sodium or chloride levels. Activated upon stimulation of G-protein coupled receptors, such as CHRM1 and GRIA1. May be regulated by calcium in the absence of sodium ions (in vitro) (By similarity).|||Phosphorylated by protein kinase C. Phosphorylation of the C-terminal domain increases channel activity (By similarity). http://togogenome.org/gene/10090:Clptm1l ^@ http://purl.uniprot.org/uniprot/Q8BXA5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CLPTM1 family.|||Endoplasmic reticulum membrane|||Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to the luminal leaflet of the ER membrane, where it participates in the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is a lipid glycoconjugate involved in post-translational modification of proteins. Can also translocate 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (phosphatidylinositol or PI), as well as several other phospholipids (1,2-diacyl-sn-glycero-3-phosphocholine, 1,2-diacyl-sn-glycero-3-phosphoethanolamine), and N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) in vitro. http://togogenome.org/gene/10090:Zer1 ^@ http://purl.uniprot.org/uniprot/Q3U297|||http://purl.uniprot.org/uniprot/Q80ZJ6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the zyg-11 family.|||Interacts with the ELOC-ELOB/Elongin BC complex. Part of an E3 ubiquitin ligase complex including ZER1, CUL2 and Elongin BC.|||Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC. Acts redudantly with ZYG11B to target substrates bearing N-terminal glycine degrons for proteasomal degradation. Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N-terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N-myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation. http://togogenome.org/gene/10090:Prdx2 ^@ http://purl.uniprot.org/uniprot/Q5M9N9|||http://purl.uniprot.org/uniprot/Q61171 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxiredoxin family.|||Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.|||Cytoplasm|||Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer (By similarity). Interacts with TIPIN (PubMed:17141802).|||The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.|||The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) instead of its condensation to a disulfide bond. It can be reactivated by forming a transient disulfide bond with sulfiredoxin SRXN1, which reduces the cysteine sulfinic acid in an ATP- and Mg-dependent manner.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2).|||Widely expressed with highest levels in bone marrow. High levels also found in heart, brain, kidney and skeletal muscle. Lower levels in liver, lung and thymus. http://togogenome.org/gene/10090:Cspp1 ^@ http://purl.uniprot.org/uniprot/B2RX88 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with PLEKHG6. Interacts with ARMC9, TOGARAM1, CCDC66, CEP104 and CEP290 (By similarity).|||May play a role in cell-cycle-dependent microtubule organization.|||Phosphorylated. Phosphorylation increases in colcemide-treated cells (By similarity).|||centrosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Tdrd3 ^@ http://purl.uniprot.org/uniprot/Q91W18 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of mRNA stress granules. Interacts with FMR1, FXR1, FXR2, EWSR1, FUS, SERBP1, EEF1A1 and DDX3X or DDX3Y, and with the small nuclear ribonucleoprotein-associated proteins SNRPB and SNRPN. Interacts with 'Lys-48'-linked tetra-ubiquitin, but not with monoubiquitin or 'Lys-63'-linked ubiquitin chains. May interact with the exon junction complex (EJC) composed at least of CASC3, EIF4A3, MAGOH and RBM8A. Interacts with POLR2A (via the C-terminal domain (CTD)).|||Cytoplasm|||Nucleus|||Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. Plays a role in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, acts as an antiviral factor that participates in the assembly of stress granules together with G3BP1.|||The Tudor domain specifically recognizes and binds asymmetric dimethylation of histone H3 'Arg-17' (H3R17me2a) and histones H4 'Arg-3', 2 tags for epigenetic transcriptional activation. http://togogenome.org/gene/10090:Ssc5d ^@ http://purl.uniprot.org/uniprot/Q8BV57 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, detected in placodes, ectodermal thickenings where organs or structures will develop. Expression levels increase substantially between 9 and 14 dpc.|||Binds to extracellular matrix proteins. Binds to pathogen-associated molecular patterns (PAMPs) present on the cell walls of Gram-positive and Gram-negative bacteria and fungi, behaving as a pattern recognition receptor (PRR). Induces bacterial and fungal aggregation and subsequent inhibition of PAMP-induced cytokine release. Does not possess intrinsic bactericidal activity. May play a role in the innate defense and homeostasis of certain epithelial surfaces.|||Cytoplasm|||Detected throughout the gastrointestinal and genitourinary tracts, in serosal salivary gland, the exocrine part of pancreas and testis, as well as in a few tubular structures in kidney. Not detected in lung and heart (at protein level). Strongly expressed in testis, kidney and pancreas, with lower levels detected in bone marrow, spleen, lung, liver, colon, stomach and skeletal muscle. Very low levels or no expression detected in thymus, esophagus, jejunum, ileum, duodenum, ovary, uterus, heart, trachea, brain, cerebellum and bladder.|||Interacts with LGALS1 and laminin.|||Partially N- and O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Vmn2r63 ^@ http://purl.uniprot.org/uniprot/E9Q0K5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnf217 ^@ http://purl.uniprot.org/uniprot/D3YYI7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RBR family. RNF217 subfamily.|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates the degradation of the iron exporter ferroportin/SLC40A1 and thus regulates iron homeostasis.|||Interacts with HAX1.|||Macrophage-specific knockout mice have increased iron export and altered ferroportin/SLC40A1 degradation.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.|||Membrane http://togogenome.org/gene/10090:Dsc1 ^@ http://purl.uniprot.org/uniprot/P55849|||http://purl.uniprot.org/uniprot/Q2VPA9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds to JUP/plakoglobin.|||Calcium may be bound by the cadherin-like repeats.|||Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. Linked to the keratinization of epithelial tissues.|||desmosome http://togogenome.org/gene/10090:Necap2 ^@ http://purl.uniprot.org/uniprot/Q9D1J1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NECAP family.|||Cell membrane|||Expressed in brain, heart, kidney, liver, lung, skeletal muscles and testis (at protein level).|||Interacts with AP1G1 and AP2A1 components of the adapter protein complexes AP-1 and AP-2. Interacts with the GAE domain proteins GGA1, GGA2 and GGA3.|||Involved in endocytosis.|||The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself (By similarity).|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Elovl1 ^@ http://purl.uniprot.org/uniprot/Q4V9V3|||http://purl.uniprot.org/uniprot/Q548M4|||http://purl.uniprot.org/uniprot/Q9JLJ5 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELO family.|||Belongs to the ELO family. ELOVL1 subfamily.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward saturated C18 to C26 acyl-CoA substrates, with the highest activity towards C22:0 acyl-CoA. May participate to the production of both saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Important for saturated C24:0 and monounsaturated C24:1 sphingolipid synthesis. Indirectly inhibits RPE65 via production of VLCFAs.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward saturated and monounsaturated acyl-CoA substrates, with the highest activity towards C22:0 acyl-CoA. May participate in the production of both saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. Important for saturated C24:0 and monounsaturated C24:1 sphingolipid synthesis. Indirectly inhibits RPE65 via production of VLCFAs.|||Endoplasmic reticulum membrane|||Expressed in a broad variety of tissues. Highly expressed in stomach, lung, kidney, skin and intestine. Moderately expressed in white adipose tissue, liver, spleen, brain, brown adipose tissue, heart and muscle. Weakly expressed in testis.|||Homozygous knockout mice die within one day after birth (PubMed:23689133). Death is caused by a skin barrier deficiency and excessive water loss that are associated with impaired formation of lipid lamellae in the stratum corneum (PubMed:23689133). In the epidermis, the levels of ceramides with fatty acid chains containing more than 26 carbons are decreased, while the levels of ceramides with less than 24 carbons are increased (PubMed:23689133).|||Interacts with LASS2, TECR and HSD17B12.|||Membrane|||The C-terminal di-lysine motif may confer endoplasmic reticulum localization.|||The substrate specificity could be slightly different compared to human ELOVL1, AC Q9BW60. No activity toward octadecanoyl-CoA, for instance, is observed in vivo (PubMed:23689133). http://togogenome.org/gene/10090:Gm13305 ^@ http://purl.uniprot.org/uniprot/P70225 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 3 subfamily.|||Expression restricted to testis, lymph node and thymus. Highest level in testis.|||Il11ra2 appears to arise through gene duplication of ancestral origin and has been lost in some inbred mouse strains.|||Membrane|||On ligand binding, forms a multimer complex with IL6ST/gp130.|||Receptor for interleukin-11. The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells. http://togogenome.org/gene/10090:Mrpl10 ^@ http://purl.uniprot.org/uniprot/Q3TBW2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL10 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ciao2b ^@ http://purl.uniprot.org/uniprot/Q9D187 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MIP18 family.|||Component of the CIA complex. Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with CIAO1, ERCC2 and MMS19; the interactions are direct. Interacts with KIF4A; the interaction facilitates the transfer of Fe-S clusters to KIF4A to ensure proper localization of KIF4A to the mitotic machinery. Interacts with CCDC117; the interaction is direct (By similarity).|||Component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. As a CIA complex component and in collaboration with CIAO1 and MMS19, binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation, probably by facilitating iron-sulfur cluster assembly into ERCC2/XPD. Together with MMS19, facilitates the transfer of Fe-S clusters to the motor protein KIF4A, which ensures proper localization of KIF4A to mitotic machinery components to promote the progression of mitosis.|||Nucleus|||spindle http://togogenome.org/gene/10090:Ammecr1 ^@ http://purl.uniprot.org/uniprot/Q9JHT5 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Exoc3l ^@ http://purl.uniprot.org/uniprot/Q8BI71 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the exocyst, may play a role in regulated exocytosis of insulin granules.|||Belongs to the SEC6 family.|||Interacts with EXOC2, EXOC4 and EXOC5; may be part of the exocyst.|||Ubiquitously expressed.|||secretory vesicle http://togogenome.org/gene/10090:P2ry6 ^@ http://purl.uniprot.org/uniprot/Q3UQ86|||http://purl.uniprot.org/uniprot/Q9ERK9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for extracellular UTP > ADP = 2-methylthio-ATP > ADP-beta-S > ATP = ATP-gamma-S. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Functionally coupled to phospholipase C (By similarity). http://togogenome.org/gene/10090:Pfdn6 ^@ http://purl.uniprot.org/uniprot/Q03958|||http://purl.uniprot.org/uniprot/Q792E4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the prefoldin subunit beta family.|||Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.|||Heterohexamer of two PFD-alpha type and four PFD-beta type subunits (By similarity). Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (By similarity). http://togogenome.org/gene/10090:Pip5k1b ^@ http://purl.uniprot.org/uniprot/P70181 ^@ Activity Regulation|||Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphatidic acid.|||Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:8798574, PubMed:9367159, PubMed:9535851, PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (By similarity). Mediates RAC1-dependent reorganization of actin filaments (PubMed:10679324). Contributes to the activation of phospholipase PLD2 (PubMed:11032811). Together with PIP5K1A, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (PubMed:18772378).|||Cell membrane|||Endomembrane system|||Highly expressed in brain and testis. Barely detectable in liver and skeletal muscle.|||Interacts with RAC1, AJUBA, PLD1, PLD2 and ARF1.|||There is confusion in the literature with phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due to the fact that frequently mouse PIP5K1B is named Phosphatidylinositol 4-phosphate 5-kinase type I alpha.|||cytosol http://togogenome.org/gene/10090:Ndnf ^@ http://purl.uniprot.org/uniprot/Q8C119 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16.5 dpc, specifically expressed in the interfollicular basal cells of the epidermis (at protein level). Detected in the marginal cells and cortical plate of the brain cortex from 16 dpc to P90 with high levels between 16 dpc and P0 and lower levels from P7 to adulthood (at protein level).|||Binds heparin and chondroitin sulfate.|||Expressed in brain and spinal cord with no expression detected in heart, kidney or liver. Expressed by neurons but not by astrocytes. In the brain, detected in the cerebrum, cerebellum and olfactory bulbs. In the cerebral cortex, highly expressed in Cajal-Retzius cells. Also expressed in hippocampal neurons and in Purkinje and granule cells of the cerebellum (at protein level) (PubMed:20969804). Expressed in neurons along the GnRH migratory route.|||Knockout mice lacking Ndnf are grossly normal and able to produce viable pups (PubMed:31883645). Absence of Ndnf in 13.5 dpc embryos results in abnormal development of the olfactory system and defective gonadotropin-releasing hormone (GnRH) expressing neurons migration to the hypothalamus (PubMed:31883645).|||N-glycosylated.|||O-glycosylated; contains heparan sulfate and chondroitin sulfate.|||Secreted|||Secretory protein that plays a role in various cellular processes. Acts as a chemorepellent acting on gonadotropin-releasing hormone (GnRH) expressing neurons regulating their migration to the hypothalamus (PubMed:31883645). Also promotes neuron migration, growth and survival as well as neurite outgrowth and is involved in the development of the olfactory system (PubMed:31883645). May also act through the regulation of growth factors activity and downstream signaling (By similarity). Also regulates extracellular matrix assembly and cell adhesiveness (PubMed:18757743). Promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms (PubMed:24706764).|||Up-regulated in endothelial cells of muscles after hind limb ischemic surgery. http://togogenome.org/gene/10090:Cabp2 ^@ http://purl.uniprot.org/uniprot/Q9JLK4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in the inner hair cells (IHCs), outer hair cells,(OHCs) and vestibular hair cells within the ear and in the retina (at protein level) (PubMed:28183797, PubMed:17947313). Expressed in the retinal cone type 6 ON-bipolar cells and type 1 OFF-bipolar cells (at protein level) (PubMed:27822497). Expressed in the organ of Corti and spiral ganglion neurons in the cochlea (at protein level) (PubMed:26809054).|||Golgi apparatus|||Mice exhibit synaptic hearing impairment and impaired auditory brainstem responses. Enhanced inactivation of Ca(2+) influx in inner hair cells (IHCs), whereas its amplitude and voltage dependence of activation is normal. Reduced normal spontaneous and sound-evoked firing of spiral ganglion neurons (SGNs) seen (PubMed:28183797). Mice exhibit normal retinal morphology but altered light responses of retinal ganglion cells (PubMed:27822497).|||Required for sound encoding at inner hair cells (IHCs) synapses, likely via inhibition of the inactivation of voltage-gated calcium channel of type 1.3 (Cav1.3) in the IHCs (PubMed:28183797). Required for the normal transfer of light signals through the retina (PubMed:27822497).|||perinuclear region http://togogenome.org/gene/10090:Tarbp2 ^@ http://purl.uniprot.org/uniprot/P97473 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TARBP2 family.|||Cytoplasm|||Nucleus|||Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. May also play a role in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA) by DICER1 (By similarity). Binds in vitro to the PRM1 3'-UTR (PubMed:8649414). Seems to act as a repressor of translation (PubMed:8649414). For some pre-miRNA substrates, may also alter the choice of cleavage site by DICER1 (PubMed:23063653). Negatively regulates IRF7-mediated IFN-beta signaling triggered by viral infection by inhibiting the phosphorylation of IRF7 and promoting its 'Lys'-48-linked ubiquitination and degradation (By similarity).|||Self-associates. Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with EIF2AK2/PKR and inhibits its protein kinase activity. Interacts with DHX9 (By similarity). Interacts with DICER1 and PRKRA (PubMed:16142218, PubMed:17452327). Interacts with DICER1, AGO2, MOV10, EIF6 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC) (By similarity). Interacts with IRF7; this interaction prevents IRF7 phosphorylation and activation (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Pgs1 ^@ http://purl.uniprot.org/uniprot/B9EKS7|||http://purl.uniprot.org/uniprot/Q8BHF7 ^@ Activity Regulation|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by calcium and magnesium and inhibited by other bivalent cations.|||Belongs to the CDP-alcohol phosphatidyltransferase class-II family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Functions in the biosynthesis of the anionic phospholipids phosphatidylglycerol and cardiolipin.|||Mitochondrion|||Widely expressed with higher expression in testis, liver and brain. http://togogenome.org/gene/10090:Sdr16c6 ^@ http://purl.uniprot.org/uniprot/Q05A13 ^@ Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. http://togogenome.org/gene/10090:Unc45a ^@ http://purl.uniprot.org/uniprot/Q99KD5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in spleen, bone marrow, lung and ovary, and at lower levels in testis, kidney, heart and brain (at protein level). Ubiquitous. Detected in uterus, large intestine, kidney, spleen, lung, brain, liver and ovary.|||Interacts with PGR isoforms A and B as well as with NR3C1 in the absence of ligand, and with HSP90AB1. Binding to HSP90AB1 involves 2 UNC45A monomers per HSP90AB1 dimer (By similarity).|||May act as co-chaperone for HSP90 (Potential). Prevents the stimulation of HSP90AB1 ATPase activity by AHSA1. Positive factor in promoting PGR function in the cell (By similarity). May be necessary for proper folding of myosin (Potential). Necessary for normal cell proliferation. Necessary for normal myotube formation and myosin accumulation during muscle cell development. May play a role in erythropoiesis in stroma cells in the spleen.|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Or5ak20 ^@ http://purl.uniprot.org/uniprot/Q7TRA1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Diaph1 ^@ http://purl.uniprot.org/uniprot/E9PV41|||http://purl.uniprot.org/uniprot/F6XC54|||http://purl.uniprot.org/uniprot/O08808 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (PubMed:10678165, PubMed:15044801, PubMed:18572016, PubMed:23558171). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (PubMed:10678165, PubMed:15044801, PubMed:18572016). Required for cytokinesis, and transcriptional activation of the serum response factor (PubMed:10678165, PubMed:15044801, PubMed:18572016). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (PubMed:10678165, PubMed:15044801, PubMed:18572016). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (PubMed:15311282). Has neurite outgrowth promoting activity (PubMed:10678165, PubMed:15044801, PubMed:18572016). Acts in a Rho-dependent manner to recruit PFY1 to the membrane (PubMed:9214622). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (By similarity). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (By similarity). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Required in the control of cell shape (By similarity). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (PubMed:23558171).|||Belongs to the formin homology family. Diaphanous subfamily.|||Cell membrane|||Cytoplasm|||Expressed in the ventricular and subventricular zone progenitor cells of the dorsal and ventral forebrain and the brainstem, at 12.5 dpc, 14.5 dpc, and 17.5 dpc. At later embryonic age, it is observed in neurons of the cortex and hippocampus. During postnatal development, expression is detected in the cerebral cortex, basal ganglia, hippocampus, thalamus, and external granular layer of the cerebellum.|||Homodimer (PubMed:14992721, PubMed:15864301). Interacts with the GTP-bound form of RHOA (PubMed:9214622). Interacts with RHOC, PFY1, MAPRE1, BAIAP2 and APC (PubMed:10814512, PubMed:15311282, PubMed:15864301). Interacts with APC; acts as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (PubMed:15311282). Interacts with SCAI (PubMed:19350017). Interacts with DCAF7, via FH2 domain (By similarity). Interacts with NCDN (PubMed:18572016). Interacts with OSBPL10, OSBPL2, VIM, TUBB and DYN1 (By similarity).|||Knockout mice show normal organization of the cerebral cortex with no significant differences in cortical white matter or callosal thickness (PubMed:24781755). Histological analysis of coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement (PubMed:24781755).|||Nucleus|||Phosphorylation at Thr-751 is stimulated by cAMP and regulates stability, complex formation and mitochondrial movement (By similarity).|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.|||Widely expressed. In the organ of Corti, it is expressed at the outer and inner hair cell layers. Expression at the inner hair cell layer is restricted to inner pillar cells. Detected in cochlear spiral ganglion neurons (PubMed:27808407).|||centrosome|||cytoskeleton|||ruffle membrane|||spindle http://togogenome.org/gene/10090:Or7g17 ^@ http://purl.uniprot.org/uniprot/Q8VGX1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem38a ^@ http://purl.uniprot.org/uniprot/Q3TMP8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM38 family.|||Expressed at high levels in heart and striated muscle. Also detected in brain, lung and kidney.|||Homotrimer; trimerization probably requires binding to phosphatidylinositol 4,5-bisphosphate (PIP2).|||Mice are viable. Mice lacking Tmem38a and Tmem38b show a weak heartbeat at E9.5 followed by loss of cardiomyocyte viability and embryonic lethality around 10.5 dpc.|||Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores.|||Nucleus membrane|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Otop1 ^@ http://purl.uniprot.org/uniprot/Q80VM9 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the otopetrin family.|||Cell membrane|||Detected in embryonic inner ear macular epithelia (PubMed:12651873). Expressed in thymus, heart, kidney, skin, vestibular system of the inner ear, sour taste cells, brown adipose tissue, heart, uterus, dorsal root ganglion, adrenal gland, lactating mammary gland and stimulated mast cells (PubMed:12651873, PubMed:29371428). Specifically expressed in sour taste cells and not other types of taste cells (PubMed:29371428).|||Mice display defects in the formation of otoconia in the inner ear, but do not suffer from deafness or other inner ear defects (PubMed:12651873). They cannot perceive gravity and have problems with spatial orientation and with keeping their equilibrium (PubMed:12651873). They show typical head-tilting behavior and are unable to swim (PubMed:12651873). Mice develop more severe diet-induced metabolic disorders: they respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation (PubMed:24379350).|||Proton-selective channel that specifically transports protons into cells (PubMed:29371428). Proton channel activity is only weakly-sensitive to voltage (PubMed:29371428). Proton-selective channel activity is probably required in cell types that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes (PubMed:29371428). In the vestibular system of the inner ear, required for the formation and function of otoconia, which are calcium carbonate crystals that sense gravity and acceleration (PubMed:12651873). Probably acts by maintaining the pH appropriate for formation of otoconia (PubMed:29371428). Regulates purinergic control of intracellular calcium in vestibular supporting cells (PubMed:17606897, PubMed:20554841). May be involved in sour taste perception in sour taste cells by mediating entry of protons within the cytosol (PubMed:29371428). Also involved in energy metabolism, by reducing adipose tissue inflammation and protecting from obesity-induced metabolic dysfunction (PubMed:24379350).|||Up-regulated in white adipose tissue in response to pro-inflammatory signaling. http://togogenome.org/gene/10090:Fcer1a ^@ http://purl.uniprot.org/uniprot/P20489 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Exhibits night/day variations with an increased expression at night in the pineal gland.|||Expressed in bone marrow mast cells, as well as in the pineal gland at night.|||High-affinity receptor for immunoglobulin epsilon/IgE. Mediates IgE effector functions in myeloid cells. Upon IgE binding and antigen/allergen cross-linking initiates signaling pathways that lead to myeloid cell activation and differentiation. On mast cells, basophils and eosinophils stimulates the secretion of vasoactive amines, lipid mediators and cytokines that contribute to inflammatory response, tissue remodeling and cytotoxicity against microbes. Triggers the immediate hypersensitivity response to allergens as a host defense mechanism against helminth parasites, pathogenic bacteria and venom toxicity. When dysregulated, it can elicit harmful life-threatening allergic and anaphylactic reactions.|||Tetramer of an alpha chain, a beta chain, and two disulfide linked gamma chains. Interacts with IGHE (via CH3 region). http://togogenome.org/gene/10090:Marchf7 ^@ http://purl.uniprot.org/uniprot/Q9WV66 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Tissue Specificity ^@ E3 ubiquitin-protein ligase which may specifically enhance the E2 activity of HIP2. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (By similarity). May be involved in T-cell proliferation by regulating LIF secretion (PubMed:15670816). May play a role in lysosome homeostasis (By similarity).|||Expressed in brain, thymus, muscle and kidney.|||Highly expressed in most tissues up to 15.5 dpc. Thereafter, expressed at highest levels in the nervous system.|||Mice have defects in formation of corpus callosum and show degeneration of substantia gelatinosa lamina II axons in adulthood. They have normal lymphoid development but show hyperproliferation of T-cells in response to mitogens.|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Ttc9b ^@ http://purl.uniprot.org/uniprot/Q9D6E4 ^@ Similarity ^@ Belongs to the TTC9 family. http://togogenome.org/gene/10090:Agtr1a ^@ http://purl.uniprot.org/uniprot/P29754 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||C-terminal Ser or Thr residues may be phosphorylated.|||Cell membrane|||Interacts with MAS1 (By similarity). Interacts with ARRB1 (By similarity). Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA (By similarity).|||Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney. The activated receptor in turn couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. http://togogenome.org/gene/10090:Tmem43 ^@ http://purl.uniprot.org/uniprot/Q9DBS1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM43 family.|||Can form oligomers through the transmembrane domains. Interacts with EMD; the interaction retains EMD at the inner nuclear membrane (PubMed:18230648). Interacts with LMNA and LMNB2 (PubMed:18230648). Interacts with SUN2. Interacts with RNF26; this interaction is important to modulate innate immune signaling through the cGAS-STING pathway. Interacts with CARD10. Interacts with gap junctions proteins GJB2/Cx26 and GJB4/Cx30 (By similarity).|||Cell membrane|||Endoplasmic reticulum membrane|||In the cochlea, mainly expressed in the organ of Corti, along the entire cochlear length, at postnatal day 4 (P4) through P20. At P20, the expression becomes more restricted to the apical membrane of the inner border cells and the cell junctions of the inner sulcus cells. Throughout the early developmental period, up to P20, expression is mainly found at inner glia-like supporting cells of Kolliker's organ, while hair cell expression is comparably sparse. Expression in glia-like supporting cells is maintained in adulthood at 1, 2 and 4 months (at protein level).|||May have an important role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. Required for retaining emerin at the inner nuclear membrane (PubMed:18230648). Plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26. In addition, functions as a critical signaling component in mediating NF-kappa-B activation by acting downstream of EGFR and upstream of CARD10 (By similarity). Contributes to passive conductance current in cochlear glia-like supporting cells, mediated by gap junctions and necessary for hearing (PubMed:34050020).|||Nucleus inner membrane|||Widely expressed, including in the cochlea, heart, eye, brain and kidney. http://togogenome.org/gene/10090:Meis3 ^@ http://purl.uniprot.org/uniprot/P97368 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TALE/MEIS homeobox family.|||Expressed at high levels in the brain. Significant expression also observed in the heart, spleen and lung. Expressed in pancreatic islets (beta-cells and non-beta-cells) (PubMed:21059917).|||Not expressed until 11 days in embryonic development.|||Nucleus|||Transcriptional regulator which directly modulates PDPK1 expression, thus promoting survival of pancreatic beta-cells. Also regulates expression of NDFIP1, BNIP3, and CCNG1. http://togogenome.org/gene/10090:Timeless ^@ http://purl.uniprot.org/uniprot/Q3U574|||http://purl.uniprot.org/uniprot/Q9R1X4 ^@ Developmental Stage|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the timeless family.|||Chromosome|||Contaminating sequence. Potential poly-A sequence.|||Expression is highest in whole embryos at 11 dpc and gradually decreases as embryonic development progresses. At 7.5 dpc, expressed in germ cell layers. At 14.5 dpc, expressed at highest levels in thymus, liver, gastrointestinal tract, lung and the rapidly proliferating ventricular zone of the brain.|||In retina, expression exhibits a circadian rhythm in the presence of light/dark cycles. In the suprachiasmatic nucleus (SCN), isoform 1 exhibited 24 hours oscillation, isoform 4 is constitutively expressed. Shows a circadian expression pattern in the intestine with peaks at ZT4 and ZT8.|||Monomer (By similarity). Homodimer or homomultimer (PubMed:12875843, PubMed:23418588). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSKN1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:9856465). Interacts directly with PER2; the interaction with PER2 is via its second PAS domain (PubMed:14564007). Interacts directly with PER1 and PER3 (PubMed:9856465, PubMed:10231394, PubMed:14564007). Interacts with CRY1 (PubMed:10428031, PubMed:23418588, PubMed:24489120). Interacts with CRY2 (PubMed:10428031). Interacts with CHEK1, ATR and ATRIP (By similarity). Interacts with CLSPN (By similarity). Interacts (via N-terminus) with TIPIN (PubMed:12875843). The TIMELESS-TIPIN heterodimer binds preferably to guanine-rich quadruplex-forming (G4) DNA structures (By similarity). Associates with the MCM2-7 complex. Interacts with DNA polymerases alpha, delta and epsilon (By similarity). Interacts with DDX11; this interaction increases recruitment of both proteins onto chromatin in response to replication stress induction by hydroxyurea (By similarity). Interacts with PARP1; interaction is direct and independent of poly-ADP-ribose (By similarity).|||Nucleus|||Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:9856465, PubMed:23418588, PubMed:10428031, PubMed:12875843, PubMed:31138685). Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:12875843). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (By similarity). TIMELESS promotes TIPIN nuclear localization (PubMed:12875843, PubMed:31138685). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 (By similarity). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:12875843). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (By similarity). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:23418588). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:10428031, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:9856465). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (PubMed:10963667).|||Predominantly and robustly expressed in proliferative organs (spleen, thymus, intestine and testis) compared to those more differentiated such as kidney and liver (at protein level). Expressed in all tissues examined including brain, heart, lung, liver, skeletal muscle, kidney, placenta, pancreas, spleen, thymus and testis. Strongly expressed in the suprachiasmatic nucleus (SCN) and pars tuberalis, moderately in the cingulate cortex, pyrimidal cell layer of the piriform cortex, periventricular part of the caudate putamen, and granular layer of the cerebellum, and weakly in the cerebral cortex, gyrus dentatus, hippocampus and thalamic nuclei. In embryonic kidney, expression is highest in regions of active ureteric bud cell branching.|||Residues 1172-1189 comprise a putative nuclear localization signal; nuclear localization is required for the regulation of period length of the circadian clock.|||The C-terminal domain, comprising the DNA-binding domain and the PARP1-binding region, is required for the replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures.|||The DNA-binding domain (residues 810-949) binds to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and has high affinity for DNA sequences rich in guanine that form G-quadruplex (G4) structures. http://togogenome.org/gene/10090:Rbm45 ^@ http://purl.uniprot.org/uniprot/Q8BHN5 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Nucleus|||RNA-binding protein with binding specificity for poly(C). May play an important role in neural development (By similarity). http://togogenome.org/gene/10090:Smim9 ^@ http://purl.uniprot.org/uniprot/Q3V0X1 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Crisp4 ^@ http://purl.uniprot.org/uniprot/E9PVG4|||http://purl.uniprot.org/uniprot/G5E862|||http://purl.uniprot.org/uniprot/Q9D259 ^@ Caution|||Similarity ^@ Belongs to the CRISP family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Thnsl2 ^@ http://purl.uniprot.org/uniprot/Q80W22 ^@ Function|||Similarity ^@ Acts as a catabolic phospho-lyase on both gamma- and beta-phosphorylated substrates. Degrades O-phospho-threonine (PThr) to alpha-ketobutyrate, ammonia and phosphate. Also degrades O-phospho-homoserine (PHS), but this is not its physiological substrate.|||Belongs to the threonine synthase family. http://togogenome.org/gene/10090:Gm5945 ^@ http://purl.uniprot.org/uniprot/A0A571BDD5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Grhpr ^@ http://purl.uniprot.org/uniprot/Q3T9Z2|||http://purl.uniprot.org/uniprot/Q91Z53 ^@ Function|||Similarity|||Subunit ^@ Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.|||Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate (By similarity).|||Homodimer. http://togogenome.org/gene/10090:Qrsl1 ^@ http://purl.uniprot.org/uniprot/Q9CZN8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).|||Belongs to the amidase family. GatA subfamily.|||Mitochondrion|||Subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (GATB) and C (GATC) subunits. http://togogenome.org/gene/10090:Avp ^@ http://purl.uniprot.org/uniprot/P35455|||http://purl.uniprot.org/uniprot/Q3UUQ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the vasopressin/oxytocin family.|||Interacts with vasopressin receptors V1bR/AVPR1B (Ki=85 pM), V1aR/AVPR1A (Ki=0.6 nM) and V2R/AVPR2 (Ki=4.9 nM) (By similarity). Interacts with oxytocin receptor (OXTR) (Ki=110 nM) (By similarity).|||Neurophysin 2 specifically binds vasopressin.|||Secreted|||Vasopressin has a direct antidiuretic action on the kidney, it also causes vasoconstriction of the peripheral vessels. Acts by binding to vasopressin receptors (V1bR/AVPR1B, V1aR/AVPR1A, and V2R/AVPR2) (By similarity). http://togogenome.org/gene/10090:Or8k35 ^@ http://purl.uniprot.org/uniprot/A0A1L1SUC9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrrc75a ^@ http://purl.uniprot.org/uniprot/Q7TSF4 ^@ Similarity ^@ Belongs to the LRRC75 family. http://togogenome.org/gene/10090:Arfrp1 ^@ http://purl.uniprot.org/uniprot/Q8BXL7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Arf family.|||Disruption of the gene leads to embryonic lethality during early gastrulation. Intestine-specific knockout mice display severe growth retardation due to reduced fat absorption and decrease in lipid release from the intestinal epithelium to the lymph and blood. Liver-specific knockout mice display impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state. Liver-specific knockout mice also display a disturbed glucose metabolism caused by a reduced plasma membrane localization of the glucose transporter GLUT2.|||Golgi apparatus|||Interacts with SYS1.|||Trans-Golgi-associated GTPase that regulates protein sorting. Controls the targeting of ARL1 and its effector to the trans-Golgi. Required for the lipidation of chylomicrons in the intestine and required for VLDL lipidation in the liver.|||trans-Golgi network http://togogenome.org/gene/10090:Or1j16 ^@ http://purl.uniprot.org/uniprot/Q8VGK4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dcun1d3 ^@ http://purl.uniprot.org/uniprot/Q8K0V2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes and may play a role in the cell cycle progression by regulating the SCF ubiquitin E3 ligase complex, after UV damage. At the cell membrane, can promote and as well inhibit cullins neddylation.|||Cytoplasm|||Nucleus|||Part of a complex containing DCUN1D3, CUL3 and RBX1. Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Interacts preferentially with CUL3; this interaction triggers the relocalization of CUL3 to the cell membrane where CUL3 is neddylated. Interacts (via DCUN1 domain) with RBX1. May also interact with regulators or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these interactions are bridged by cullins. Interacts (via DCUN1 domain) with CAND1; this interaction is bridged by cullins and strongly inhibits cullin neddylation. These CAND-cullin-DCNL complexes can only be neddylated in the presence of a substrate adapter. Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F.|||The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities. This domain is also involved in CAND1-, cullins- and RBX1-binding.|||perinuclear region http://togogenome.org/gene/10090:Tcta ^@ http://purl.uniprot.org/uniprot/A0A0A6YXI4|||http://purl.uniprot.org/uniprot/Q8VEA7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Although demonstrated for the human ortholog, involvement in osteoclastogenesis failed to be demonstrated in mouse cells.|||Belongs to the TCTA family.|||May be required for cellular fusion during osteoclastogenesis.|||Membrane http://togogenome.org/gene/10090:Unc5d ^@ http://purl.uniprot.org/uniprot/A0A1B0GSR6|||http://purl.uniprot.org/uniprot/A6H5Z5|||http://purl.uniprot.org/uniprot/B7ZMT2|||http://purl.uniprot.org/uniprot/C5IAW8|||http://purl.uniprot.org/uniprot/Q8K1S2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the unc-5 family.|||Cell membrane|||Detected in multipolar cells in the brain subventricular zone (at protein level) (PubMed:18547816). Detected in embryonic brain neocortex, especially in the subventricular zone (PubMed:21673655). Detected in multipolar cells in the brain subventricular zone (PubMed:18547816). Detected in brain neocortex from young pups, especially in the somatosensory cortex (PubMed:21216843). Expressed in developing limb and mammary gland (PubMed:12351186).|||Interacts (via extracellular domain) with FLRT2 and FLRT3 (via extracellular domain); the interaction is direct (PubMed:19492039, PubMed:21673655, PubMed:25374360, PubMed:26235030). Has higher affinity for FLRT2 (PubMed:25374360). Identified in a complex with FLRT3 and ADGRL3; does not interact with ADGRL3 by itself (PubMed:26235030).|||Membrane|||No visible phenotype. Mice are viable, appear healthy, and do not display any obvious behavorial defects. Cortical neurons from mutant mice display impaired axon growth cone collapse in response to Flrt2 and a tendency towards accelerated radial migration in the developing brain.|||Proteolytically cleaved by caspases during apoptosis. The cleavage does not take place when the receptor is associated with netrin ligand. Its cleavage by caspases is required to induce apoptosis (By similarity).|||Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding.|||Receptor for the netrin NTN4 that promotes neuronal cell survival (PubMed:21216843). Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration (By similarity). Plays a role in the regulation of neuronal cell migration in the developing brain via its interaction with FLRT2 (PubMed:21673655). Plays a role in axon guidance by mediating axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (PubMed:21673655). May play a role in apoptosis in response to DNA damage. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates cell-cell adhesion via its interaction with FLRT3 on an adjacent cell (PubMed:26235030). http://togogenome.org/gene/10090:Zfp521 ^@ http://purl.uniprot.org/uniprot/Q6KAS7 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Defects in Znf521 are a cause of B-cell lymphomas. The Znf521 gene is a frequent target of retroviral integration in murine B-cell lymphomas. Involved in most B-cell tumors in the AKXD-27 strain. Viral insertion into the Znf521 gene in the AKXD-27 strain causes Znf521 overexpression in B-cell tumors, resulting in the up-regulation of EBF1 and the increased expression of a number of EBF1 target genes. This in contrast to the role of Znf521 in other cells as a transcriptional repressor of EBF1. Misexpression initiates tumorigenesis by perturbing B-cell development via an interaction with EBF1.|||Interacts with EBF1. Interacts with SMAD1 and SMAD4 (By similarity).|||Nucleus|||Transcription factor that can both act as an activator or a repressor depending on the context. Involved in BMP signaling and in the regulation of the immature compartment of the hematopoietic system. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved specification of B-cell lineage; this interaction preventing EBF1 to bind DNA and activate target genes.|||Uses different DNA- and protein-binding zinc fingers to regulate the distinct BMP-Smad and hematopoietic system.|||Widely expressed. Expressed in all B-cell stages. http://togogenome.org/gene/10090:Usp21 ^@ http://purl.uniprot.org/uniprot/E9PUE2|||http://purl.uniprot.org/uniprot/Q9QZL6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Belongs to the peptidase C19 family. USP21 subfamily.|||Cytoplasm|||Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator (PubMed:18172164). Deubiquitination of histone H2A releaves the repression of di- and trimethylation of histone H3 at 'Lys-4', resulting in regulation of transcriptional initiation (PubMed:18172164). Regulates gene expression via histone H2A deubiquitination (PubMed:18172164). Deubiquitinates BAZ2A/TIP5 leading to its stabilization (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates (By similarity). Also acts as a negative regulator of the ribosome quality control (RQC) by mediating deubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS20/uS10, thereby antagonizing ZNF598-mediated 40S ubiquitination (By similarity).|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Interacts with BEND3.|||Nucleus http://togogenome.org/gene/10090:Mtrf1 ^@ http://purl.uniprot.org/uniprot/Q8K126 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the prokaryotic/mitochondrial release factor family.|||Methylation of glutamine in the GGQ triplet by HEMK1 is conserved from bacteria to mammals.|||Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain non-canonical stop codons AGG and AGA. Non-canonical termination codons AGG and AGA are found at the end of MT-CO1/COX1 and MT-ND6/ND6 open reading frames, respectively. Recognizes non-canonical stop codons via a network of interactions between the codon, MTRF1 and the ribosomal RNA (rRNA): in contrast to other translation release factors, which identify the codon in the A-site via direct interactions of amino acid side chains with the bases, MTRF1 repositions the first 2 bases of the stop codon to use an intricate network of interactions that includes residues of the release factor, the rRNA of the small ribosomal subunit, as well as neighboring bases of the mRNA.|||Mitochondrion|||The GGQ domain interacts with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis. http://togogenome.org/gene/10090:Vwa7 ^@ http://purl.uniprot.org/uniprot/Q9JHA8 ^@ Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed at low level in many tissues.|||Recombinatorial hotspot within the class III region.|||Secreted http://togogenome.org/gene/10090:Wnt2 ^@ http://purl.uniprot.org/uniprot/P21552|||http://purl.uniprot.org/uniprot/Q8BRC7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Wnt family.|||Detected in ventral mesencephalon from 10.5 to 15.5 dpc; expression levels decrease moderately, but steadily during this period (PubMed:20018874). Detected in the lateral plate mesoderm surrounding the ventral aspect of the anterior foregut from 9.0 to 10.5 dpc (PubMed:19686689). Detected in the developing mesenchyme with higher levels surrounding the distal regions of the branching airways from 12.5 to 18.5 dpc (PubMed:19686689).|||In embryos in the developing allantois, pericardium heart, and ventral-lateral mesoderm; in adults in lung, brain, heart and placenta.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:19686689). Functions as upstream regulator of FGF10 expression (PubMed:19686689). Plays an important role in embryonic lung development (PubMed:19686689). May contribute to embryonic brain development by regulating the proliferation of dopaminergic precursors and neurons (PubMed:20018874).|||Nearly complete perinatal lethality within minutes after birth, due to lung hypoplasia (PubMed:19686689). About 4% survive for more than 30 days (PubMed:19686689). Combined disruption of Wnt2 and Wnt2b leads to lung agenesis and loss of trachea development (PubMed:19686689). In contrast, development of liver, stomach, intestine, pancreas and kidneys appears grossly normal (PubMed:19686689).|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Tmc1 ^@ http://purl.uniprot.org/uniprot/Q8R4P5 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMC family.|||Cell membrane|||Defects in Tmc1 are the cause of recessive deaf mutant dn. The dn mutant shows profound deafness with degeneration of the organ of Corti, stria vascularis, and occasionally the saccular macula, starting at about 10 days after birth (PubMed:11850618).|||Defects in Tmc1 are the cause of the dominant deaf mutant Beethoven (BTH). Heterozygotes show progressive hair-cell degeneration from day 20 onwards, leading to severe depletion of inner hair cells and scattered loss of outer hair cells, and progressive loss of the Preyer reflex from around day 30. Homozygotes show almost complete degeneration of inner hair cells, and little or no Preyer reflex at any age.|||Detected in cochlear inner and outer hair cells and in neurosensory epithelia of the vestibular end organs. Also expressed in cortex, cerebellum, eye, colon, ovary and testis.|||Expressed at low, constant levels in temporal bone from embryonic day 14 to day 1 after birth. Increases by 8 to 16-fold at day 5, 10 and 20 and continues to be expressed up to day 90.|||Interacts with TOMT (PubMed:28504928, PubMed:28534737). The interaction of TMC1 and TMC2 with TOMT is required for the transportation of TMC1/2 into the stereocilia of hair cells (PubMed:28504928, PubMed:28534737). Interacts (via N-terminus) with both isoforms CD1 and CD3 of PCDH15 (PubMed:25114259). Interacts with CIB2 (PubMed:28663585, PubMed:34089643). Interacts with CIB3 (PubMed:34089643).|||Probable ion channel required for the normal function of cochlear hair cells. http://togogenome.org/gene/10090:Fut11 ^@ http://purl.uniprot.org/uniprot/B2RRR9|||http://purl.uniprot.org/uniprot/Q8BHC9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 10 family.|||Golgi stack membrane|||Has fucosyltransferase activity toward biantennary N-glycan acceptors. Does not fucosylate GlcNAc residue within type 2 lactosamine unit.|||Membrane|||Predominantly fucosylates the innermost N-acetyl glucosamine (GlcNAc) residue in biantennary N-glycan acceptors.|||Widely expressed. Expressed at slightly higher level in heart, kidney and lung. http://togogenome.org/gene/10090:Cpne7 ^@ http://purl.uniprot.org/uniprot/Q0VE82 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the copine family.|||Calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.|||Cell membrane|||Cytoplasm|||Nucleus|||The C2 domain 1 is not necessary for calcium-mediated translocation and association to the plasma membrane. The C2 domain 2 is necessary for calcium-mediated translocation and association to the plasma membrane. http://togogenome.org/gene/10090:Ccdc69 ^@ http://purl.uniprot.org/uniprot/Q3TCJ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CCDC69 family.|||May act as a scaffold to regulate the recruitment and assembly of spindle midzone components. Required for the localization of AURKB and PLK1 to the spindle midzone.|||Midbody|||spindle http://togogenome.org/gene/10090:Vmn1r122 ^@ http://purl.uniprot.org/uniprot/K7N726 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpr107 ^@ http://purl.uniprot.org/uniprot/Q148Z6|||http://purl.uniprot.org/uniprot/Q8BUV8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LU7TM family.|||Cell membrane|||Cleaved by FURIN to yield two fragments that remain associated via a disulfide bond.|||Has been proposed to act as a receptor for neuronostatin, a peptide derived from the somatostatin/SST precursor (By similarity). Involved in blood sugar regulation through the induction of glucagon in response to low glucose (By similarity).|||Membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Lsm12 ^@ http://purl.uniprot.org/uniprot/Q9D0R8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LSM12 family.|||Cytoplasm|||Found in a complex with LSM12, TPCN1 and TPCN2. Interacts with TPCN2.|||Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein. Confers NAADP sensitivity to the two pore channel complex (TPCs) by acting as TPC accessory protein necessary for NAADP-evoked Ca(2+) release. http://togogenome.org/gene/10090:Hcn4 ^@ http://purl.uniprot.org/uniprot/B2RY58 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the potassium channel HCN family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrp6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0A9|||http://purl.uniprot.org/uniprot/O88572 ^@ Caution|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LDLR family.|||Cell membrane|||Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes.|||Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalosomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity).|||Defects in Lrp6 are the cause of Ringelschwanz (rs) phenotype. Rs phenotype is a spontaneous mutation that is characterized by a combination of multiple Wnt-deficient phenotypes including dysmorphologies of the axial skeleton, digits and the neural tube. The establishment of the anteroposterior somite compartments, the epithelialization of nascent somites, and the formation of segment borders are disturbed in (rs) mutants. There is delayed ossification at birth and a low bone mass phenotype in adults. Functional analyses reveal impaired targeting to the plasma surface due to reduced interaction with MESD leading to inhibited Wnt/beta-catenin signaling.|||Dual phosphorylation of cytoplasmic PPPSP motifs sequentially by GSK3 and CK1 is required for AXIN1-binding, and subsequent stabilization and activation of beta-catenin via preventing GSK3-mediated phosphorylation of beta-catenin. Phosphorylated, in vitro, by GRK5/6 within and outside the PPPSP motifs. Phosphorylation at Ser-1490 by CDK14 during G2/M phase leads to regulation of the Wnt signaling pathway during the cell cycle. Phosphorylation by GSK3B is induced by RPSO1 binding and inhibited by DKK1. Phosphorylated, in vitro, by casein kinase I on Thr-1479 (By similarity).|||Endoplasmic reticulum|||Expressed in early embryo. Broadly expressed throughout the embryonic ectoderm and in nascent mesoderm, and in endoderm emerging from the primitive streak.|||Homodimer; disulfide-linked (By similarity). Forms phosphorylated oligomer aggregates on Wnt-signaling (By similarity). Component of the Wnt-Fzd-LRP5-LRP6 complex. Interacts (via the extracellular domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and DRAXIN. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalosomes. Interacts (via the extracellular domain) with RSPO1; the interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta-propeller regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling. Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin (By similarity). Interacts with DRAXIN; the interaction inhibits Wnt signaling. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane. Interacts with MACF1. Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Interacts with TMEM198 (By similarity). Interacts with CAPRIN2; the interaction promotes LRP6 phosphorylation at Ser-1490 (By similarity). Found in a complex with CAPRIN2, CCNY and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus. Interacts with LYPD6 (via NxI motif) (By similarity). Forms a ternary complex with DKK1 and KREM1 (By similarity). Interacts with KREM1 in a DKK1-dependent manner (By similarity). Interacts with MDK: this interaction is calcium dependent (PubMed:12573468). Interacts with LMBR1L (PubMed:31073040).|||Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Membrane raft|||Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome (By similarity).|||N-glycosylation is required for cell surface location.|||Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.|||The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.|||The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1 (By similarity).|||Undergoes gamma-secretase-dependent regulated intramembrane proteolysis (RIP). The extracellular domain is first released by shedding, and then, through the action of gamma-secretase, the intracellular domain (ICD) is released into the cytoplasm where it is free to bind to GSK3B and to activate canonical Wnt signaling (By similarity). http://togogenome.org/gene/10090:Ptgfr ^@ http://purl.uniprot.org/uniprot/P43117|||http://purl.uniprot.org/uniprot/Q60I90|||http://purl.uniprot.org/uniprot/Q8BNT7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum (By similarity). http://togogenome.org/gene/10090:Ets2 ^@ http://purl.uniprot.org/uniprot/P15037|||http://purl.uniprot.org/uniprot/Q3UP99 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ETS family.|||Nucleus|||Phosphorylation by CDK10 at Ser-220 and Ser-225 creates a phosphodegron that targets ETS2 for proteasomal degradation.|||Transcription factor activating transcription. Binds specifically the GGA DNA motif in gene promoters and stimulates transcription of those genes (By similarity).|||Transcription factor. http://togogenome.org/gene/10090:Mospd1 ^@ http://purl.uniprot.org/uniprot/Q3UT40|||http://purl.uniprot.org/uniprot/Q8VEL0 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Expressed at low levels in undifferentiated mesenchymal stem cells and then shows increasing expression levels as differentiation proceeds.|||Golgi apparatus membrane|||May be up-regulated in response to cell-cell contact.|||Membrane|||Plays a role in differentiation and/or proliferation of mesenchymal stem cells (PubMed:21792907, PubMed:26175344). Proposed to be involved in epithelial-to-mesenchymal transition (EMT) (PubMed:21792907). However, another study suggests that it is not required for EMT or stem cell self-renewal and acts during later stages of differentiation (PubMed:26175344).|||Widely expressed. Shows highest expression in ribs, and slightly lower levels of expression in heart, kidney, muscle, thymus, calvariae and lung. Also detected at low levels in spleen and liver. http://togogenome.org/gene/10090:Mis18bp1 ^@ http://purl.uniprot.org/uniprot/Q80WQ8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with SP1. Interacts with MIS18A. Identified in a complex containing MIS18A, OIP5/MIS18B, MIS18BP1, RBBP7 and RBBP4. Interacts with KAT7/HBO1 (By similarity). Interacts (via N-terminus) with FLNA (via N-terminus) (PubMed:21228480).|||Nucleus|||Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.|||centromere http://togogenome.org/gene/10090:Ranbp1 ^@ http://purl.uniprot.org/uniprot/P34022 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the RANBP1 family.|||Htf9a (RanBP1) and Htf9c are transcribed with opposite polarity from complementary DNA strands from a shared bidirectional TATA-less promoter.|||Interacts with RAN (via C-terminus of GTP-bound form) but not with GDP-bound RAN (PubMed:8255297, PubMed:7891706, PubMed:8896452). Identified in a complex composed of RAN, RANGAP1 and RANBP1 (By similarity). Identified in a complex that contains TNPO1, RAN and RANBP1 (PubMed:9428644). Identified in a complex that contains CSE1L, KPNA2, RAN and RANBP1 (PubMed:9428644). Identified in a complex with nucleotide-free RAN and RCC1 (By similarity).|||Plays a role in RAN-dependent nucleocytoplasmic transport. Alleviates the TNPO1-dependent inhibition of RAN GTPase activity and mediates the dissociation of RAN from proteins involved in transport into the nucleus (PubMed:9428644). Induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (By similarity). Promotes the disassembly of the complex formed by RAN and importin beta. Promotes dissociation of RAN from a complex with KPNA2 and CSE1L (PubMed:9428644). Required for normal mitotic spindle assembly and normal progress through mitosis via its effect on RAN (By similarity). Does not increase the RAN GTPase activity by itself, but increases GTP hydrolysis mediated by RANGAP1 (PubMed:9428644). Inhibits RCC1-dependent exchange of RAN-bound GDP by GTP (By similarity). http://togogenome.org/gene/10090:Pcdhga1 ^@ http://purl.uniprot.org/uniprot/Q91XZ0 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Acsl5 ^@ http://purl.uniprot.org/uniprot/Q3UC67|||http://purl.uniprot.org/uniprot/Q8JZR0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (By similarity). ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage (By similarity). It was suggested that it may also stimulate fatty acid oxidation (By similarity). At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL (By similarity). May have a role in the survival of glioma cells (By similarity). Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids (By similarity).|||Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation.|||Cell membrane|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Membrane|||Mitochondrion|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Crbn ^@ http://purl.uniprot.org/uniprot/Q8C7D2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRBN family.|||Component of a DCX (DDB1-CUL4-X-box) protein ligase complex, at least composed of CRBN, CUL4A, DDB1 and RBX1. Interacts directly with DDB1 (By similarity). Interacts with KCNT1 (By similarity). Interacts with ILF2 (By similarity). Interacts with TRAF6 and ECSIT (By similarity).|||Cytoplasm|||Highly expressed in brain.|||In brain, expression is abundant in the cerebellum, with less expression in the neocortical, hippocampus and striatum in adult. Neocortical expression increases from embryonic stages to adulthood.|||Membrane|||No obvious phenotype, however mice display increased BK channel activity and a subsequent decrease in synaptic transmission and presynaptic release probability in excitatory synapses (PubMed:29530986). Mice also display cognitive behavioral defects such as abnormal passive avoidance, hyperanxious behavior and decreased preference for new objects (PubMed:29530986). Treatment with the BK blocker paxilline rescues all synaptic and behavioral abnormalities except for hyperanxiety (PubMed:29530986). Brain and synaptic morphology is normal and long-term synaptic plasticity is not affected (PubMed:29530986). Conditional knockout in the forebrain results in no obvious phenotype, however mice display a deficit in contextual fear learning whereas anxiety-like behavior is unaffected (PubMed:21995942).|||Nucleus|||Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 or ILF2. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (By similarity). Maintains presynaptic glutamate release and consequently, cognitive functions such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (By similarity). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (PubMed:29530986). Plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, leading to inhibition of ECSIT ubiquitination, an important step of the signaling (By similarity).|||The CULT domain binds thalidomide and related drugs. Thalidomide binding leads to a change in substrate specificity of the human DCX (DDB1-CUL4-X-box) E3 protein ligase complex, while no such change is observed in rodents.|||Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex. http://togogenome.org/gene/10090:Dennd3 ^@ http://purl.uniprot.org/uniprot/A2RT67 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Forms oligomers (PubMed:28249939). Interacts with 6 of the 7 known isoforms of 14-3-3 proteins (PubMed:25925668).|||Guanine nucleotide exchange factor (GEF) activating Rab12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab12 into its active GTP-bound form. Regulates autophagy in response to starvation through Rab12 activation (PubMed:24719330, PubMed:25925668, PubMed:28249939). Starvation leads to ULK1/2-dependent phosphorylation of Ser-554 and Ser-572, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards Rab12 (PubMed:25925668). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:21718402, PubMed:24719330). Starvation also induces phosphorylation at Tyr-940, which leads to up-regulated GEF activity and initiates autophagy (PubMed:28249939).|||Inactive Dennd3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-940 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards Rab12. http://togogenome.org/gene/10090:Ift20 ^@ http://purl.uniprot.org/uniprot/Q61025 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cells that stably express short interference RNAs targeting IFT20 show reduced centriolar IFT20 and lack primary cilia.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:12821668, PubMed:16775004, PubMed:19253336). Interacts directly with IFT57 and KIF3B/Kinesin II subunit (PubMed:12821668). Interacts with IFT88 (PubMed:19253336). Interacts with CEP83 (By similarity). Interacts with SPEF2 (via C-terminus) (PubMed:19889948). Interacts with CBL and CBLB (By similarity). Interacts with TRIP11 (PubMed:19112494). Interacts with TTC21A (By similarity). Interacts with SPATA1 (PubMed:31816150). Interacts with USH1G (By similarity).|||Conditional knockout in male germ cells results in infertility, abnormal sperm morphology, significantly reduced sperm count and sperm mobility.|||Cytoplasm|||Expressed predominantly in the testis (at protein level). Expressed in kidney and retina. Expression is up-regulated during spermiogenesis.|||Expression is first detected at postnatal day 16 (P16) and increases significantly at days P30 and P42.|||Golgi apparatus|||Part of intraflagellar transport (IFT) particles involved in ciliary process assembly. May play a role in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium (PubMed:16775004). Regulates the ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway. Required for protein stability of E3 ubiquitin ligases CBL and CBLB that mediate ubiquitination and internalization of PDGFRA for proper feedback inhibition of PDGFRA signaling (PubMed:29237719). Essential for male fertility. Plays an important role in spermatogenesis, particularly spermiogenesis, when germ cells form flagella. May play a role in the transport of flagellar proteins ODF2 and SPAG16 to build sperm flagella and in the removal of redundant sperm cytoplasm (PubMed:27682589). Also involved in autophagy since it is required for trafficking of ATG16L and the expansion of the autophagic compartment (PubMed:24089209).|||acrosome|||centriole|||cilium|||cilium basal body|||cis-Golgi network|||cytoskeleton http://togogenome.org/gene/10090:Zfp784 ^@ http://purl.uniprot.org/uniprot/Q8BI69 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Oog3 ^@ http://purl.uniprot.org/uniprot/Q3UWY1 ^@ Similarity|||Tissue Specificity ^@ Belongs to the PRAME family.|||Expressed in ovary, specifically in oocytes. Detected in follicles with two layers of granulosa cells, and are present in early as well as large antral follicles. http://togogenome.org/gene/10090:Bmp5 ^@ http://purl.uniprot.org/uniprot/P49003|||http://purl.uniprot.org/uniprot/Q3UXE6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Deletion mutant mice show a number of skeletal defects, including small ears, several reduced vertebral processes, and a reduced number of ribs and sesamoid bones (PubMed:7958439). BMP5/7-deficient mice lack midbrain dopaminergic neurons due to reduced neurogenesis in the midbrain dopaminergic progenitor domain (PubMed:29321139).|||Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cartilage and bone formation or neurogenesis (PubMed:7958439, PubMed:29321139). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Can also signal through non-canonical pathway such as MAPK p38 signaling cascade to promote chondrogenic differentiation (By similarity). Promotes the expression of HAMP, this is repressed by its interaction with ERFE (PubMed:30097509).|||Interacts with ERFE; the interaction inhibits BMP-induced transcription of HAMP.|||Secreted http://togogenome.org/gene/10090:Lrp3 ^@ http://purl.uniprot.org/uniprot/E9Q1T6|||http://purl.uniprot.org/uniprot/E9Q711|||http://purl.uniprot.org/uniprot/Q3UEV4 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:H4c17 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Fam216b ^@ http://purl.uniprot.org/uniprot/Q8CC14 ^@ Similarity ^@ Belongs to the FAM216 family. http://togogenome.org/gene/10090:Asph ^@ http://purl.uniprot.org/uniprot/A2AL74|||http://purl.uniprot.org/uniprot/A2AL75|||http://purl.uniprot.org/uniprot/A2AL76|||http://purl.uniprot.org/uniprot/A2AL78|||http://purl.uniprot.org/uniprot/A2AL81|||http://purl.uniprot.org/uniprot/A2AL85|||http://purl.uniprot.org/uniprot/Q3TU40|||http://purl.uniprot.org/uniprot/Q8BQK0|||http://purl.uniprot.org/uniprot/Q8BSY0|||http://purl.uniprot.org/uniprot/Q8CBM2|||http://purl.uniprot.org/uniprot/Q9CR06|||http://purl.uniprot.org/uniprot/Q9D7J8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aspartyl/asparaginyl beta-hydroxylase family.|||Endoplasmic reticulum membrane|||Isoform 1 is detected in heart, liver and ovary (at protein level). Detected in heart ventricle. Isoform 1 is widely expressed. Isoform 2 is detected in heart and skeletal muscle.|||Membrane|||Monomer. Isoform 2 interacts with CASQ2.|||Sarcoplasmic reticulum membrane|||Selective disruption of isoform 1 abolishes liver aspartyl beta-hydroxylase activity, but does not affect the expression of isoform 2. Mice lacking isoform 1 have normal blood chemistry, do not present blood coagulation defects and appear more or less normal, except for shorter snouts, mild defects of the palate ridges, syndactily due to fusion of soft tissues and reduced litter size from mutant females, while male fertility appears normal. Mice lacking isoform 2 show no visible phenotype.|||Specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins.|||Strongly expressed in the snout, limbs and eye of 11.5 dpc and 12 dpc. Strong localization of the protein in the lens of the developing eye at all three stages. http://togogenome.org/gene/10090:Pkd2 ^@ http://purl.uniprot.org/uniprot/O35245 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the polycystin family.|||Cell membrane|||Channel activity is regulated by phosphorylation (By similarity). The channel is activated by increased cytoplasmic Ca(2+) (in the uM range) and by membrane depolarization (PubMed:27760766).|||Complete embryonic lethality, with most embryos surviving up to about 16.5 dpc (PubMed:9568711, PubMed:10615132, PubMed:12062060). Embryos lacking Pkd2 develop normally up to 13.5 dpc, but after that about half of them display total body edema and focal hemorrhages (PubMed:10615132). Mutant embryos display defects in left-right laterality, including abnormal heart looping (PubMed:12062060). After 13.5 dpc, all embryos display defects in heart development, with defective formation of the interventricular septum (PubMed:10615132, PubMed:12062060). Besides, many display defective formation of the atrial septum and pericardial effusions (PubMed:10615132). After 14.5 dpc, the embryos display progressive cystic dilatation of pancreatic ducts (PubMed:10615132). After 15.5 dpc, they display progressive kidney cyst formation (PubMed:10615132). In contrast, liver development is normal, without any cyst formation (PubMed:10615132). Heterozygous mice with one null allele and one instable allele that leads to somatic loss of Pkd2 expression due to intragenic recombination all display bilateral renal cysts at an age of about 11 weeks (PubMed:9568711). These cysts cover 25-75% of the cut surface area of each kidney (PubMed:9568711). Progressive cyst formation leads eventually to renal failure and shortened lifespan (PubMed:10615132). Besides, these mice all display liver cysts and half of them display also bile duct proliferation (PubMed:9568711). About half of the heterozygous mice with one null allele and one instable allele that leads to somatic loss of Pkd2 expression due to intragenic recombination display visible pancreas cysts at an age of three months (PubMed:10615132). Mice homozygous for an instable allele that leads to somatic loss of Pkd2 expression due to intragenic recombination develop renal cysts that arise from cells that have lost Pkd2 expression (PubMed:9568711). Heterozygous mice that bear one null allele also have a reduced lifespan, but this is not due to kidney failure (PubMed:10615132).|||Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. Can also form a functional, homotetrameric ion channel (PubMed:27214281). Functions as a cation channel involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:12514735, PubMed:18695040, PubMed:27760766, PubMed:31048699). Functions as outward-rectifying K(+) channel, but is also permeable to Ca(2+), and to a much lesser degree also to Na(+) (PubMed:27760766). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (By similarity). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). PKD1 and PKD2 may function through a common signaling pathway that is necessary to maintain the normal, differentiated state of renal tubule cells (PubMed:9568711, PubMed:10615132). Acts as a regulator of cilium length, together with PKD1. The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (PubMed:20096584). Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning (PubMed:21307093, PubMed:22983710). Detection of asymmetric nodal flow gives rise to a Ca(2+) signal that is required for normal, asymmetric expression of genes involved in the specification of body left-right laterality (PubMed:12062060, PubMed:21307093, PubMed:22983710).|||Cytoplasmic vesicle membrane|||Detected in kidney epithelium (at protein level) (PubMed:9568711, PubMed:10770959, PubMed:11854751). Highly expressed on basolateral membranes in distal convoluted tubules and medullary thick ascending limbs of Henle (PubMed:9568711). Detected at much lower levels in cortical and medullary collecting tubules, and not detected in the glomerular tuft, in thin limbs of Henle, interstitium and blood vessels (at protein level) (PubMed:9568711). Expressed in mesenchymally derived structures in the developing embryo at day 12.5. Isoform 1 is predominantly expressed in kidney at all developmental stages with high levels also detected in lung. Isoform 3 shows highest expression in brain with lower expression in kidney and lung, low levels in thymus and is hardly detectable in liver.|||Endoplasmic reticulum membrane|||Golgi apparatus|||Homotetramer. Heterotetramer with PKD1, giving rise to a complex formed by one PKD1 chain and three PKD2 chains (By similarity). Interaction with PKD1 is required for ciliary localization (PubMed:25405894). Isoform 1 interacts with PKD1 while isoform 3 does not (PubMed:16192288). Interacts with PKD1L1 (PubMed:21307093, PubMed:22983710). PKD1 requires the presence of PKD2 for stable expression (PubMed:16192288). Interacts with CD2AP (PubMed:10913159). Interacts with HAX1 (PubMed:10760273). Interacts with NEK8 (PubMed:18235101). Part of a complex containing AKAP5, ADCY5, ADCY6 and PDE4C (PubMed:21670265). Interacts (via C-terminus) with TRPV4 (via C-terminus) (PubMed:18695040). Interacts (via C-terminal acidic region) with PACS1 and PACS2; these interactions retain the protein in the endoplasmic reticulum and prevent trafficking to the cell membrane (PubMed:15692563). Interacts with TMEM33 (PubMed:31048699).|||Minor isoform.|||N-glycosylated (PubMed:11854751). The four subunits in a tetramer probably differ in the extent of glycosylation; simultaneous glycosylation of all experimentally validated sites would probably create steric hindrance (By similarity).|||Phosphorylated (PubMed:16551655). Phosphorylation is important for protein function; a mutant that lacks the N-terminal phosphorylation sites cannot complement a zebrafish pkd2-deficient mutant. PKD-mediated phosphorylation at the C-terminus regulates its function in the release of Ca(2+) stores from the endoplasmic reticulum. PKA-mediated phosphorylation at a C-terminal site strongly increases the open probability of the channel, but does not increase single channel conductance.|||The C-terminal coiled-coil domain is involved in oligomerization and the interaction with PKD1. The isolated coiled-coil domain forms a homotrimer in vitro; the homotrimer interacts with a single PKD1 chain. The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro).|||Ubiquitous in embryos at the early somite stage.|||cilium membrane http://togogenome.org/gene/10090:Gan ^@ http://purl.uniprot.org/uniprot/Q8CA72 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain, heart and muscle (at protein level).|||Interacts with TBCB. Interacts with CUL3. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with UBA1 (By similarity). Interacts (via Kelch domains) with MAP1B (via C-terminus) and MAP1S (via C-terminus).|||Mice have a relatively normal life span. However, they display deterioration in motor function with onset varying from 6 to 10 months as well as abnormalities in non-neuronal tissues. The prominent pathological features include limb weakness, muscular atrophy, axonal degeneration, neurofilament accumulation, an abnormal microtubule network, mitochondrial swelling and thinned myelin sheaths.|||Probable cytoskeletal component that directly or indirectly plays an important role in neurofilament architecture. May act as a substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Controls degradation of TBCB (By similarity). Controls degradation of MAP1B and MAP1S, and is critical for neuronal maintenance and survival.|||Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and RBX1 and probably targeted for proteasome-independent degradation.|||cytoskeleton http://togogenome.org/gene/10090:Ppia ^@ http://purl.uniprot.org/uniprot/P17742|||http://purl.uniprot.org/uniprot/Q5SVY2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization (By similarity). PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition (By similarity). Acetylation at Lys-125 favors the interaction with TARDBP (By similarity).|||Belongs to the cyclophilin-type PPIase family.|||Belongs to the cyclophilin-type PPIase family. PPIase A subfamily.|||Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase.|||Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:24429998). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (By similarity). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (By similarity). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (By similarity). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (By similarity). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (PubMed:24429998). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (PubMed:24429998). Binds heparan sulfate glycosaminoglycans (By similarity).|||Cytoplasm|||Expressed in the kidney thick ascending limb (at protein level) (PubMed:25967121). Expressed in neurons and motor neurons (at protein level) (PubMed:25678563). Expressed in platelets (PubMed:24429998).|||Interacts with protein phosphatase PPP3CA/calcineurin A (By similarity). Interacts with PRPF19 isoform 2 (via N-terminus) (PubMed:16352598). Interacts with isoform 2 of BSG/CD147 (By similarity). Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (By similarity). Interacts with integrin ITGA2B:ITGB3; the interaction is ROS and PPIase activity-dependent and is increased in the presence of thrombin (PubMed:24429998). Interacts with MAP3K5 (By similarity). Interacts with TARDBP (PubMed:25678563). The interaction with TARDBP is dependent on the RNA-binding activity of TARDBP and the PPIase activity of PPIA/CYPA and the acetylation of PPIA/CYPA at Lys-125 favors the interaction (By similarity). Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM (By similarity).|||Mice exhibit prolonged tail bleeding time compared to wild-type mice despite equivalent platelet numbers (PubMed:24429998). Platelets exhibit significantly reduced thrombin-induced platelet aggregation and activation, ROS production, calcium mobilization and activation of integrin ITGA2B:ITGB3 (PubMed:24429998). Fibrinogen-platelet binding, platelet spreading and cytoskeleton reorganization are also impaired (PubMed:24429998).|||Nucleus|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.|||Secreted http://togogenome.org/gene/10090:Brinp3 ^@ http://purl.uniprot.org/uniprot/Q499E0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BRINP family.|||Expressed in the brain. Weakly expressed in embryonic stem (ES) cells. Expressed in ES-derived neural stem cells (NSCs) and neuronal cells.|||Inhibits neuronal cell proliferation by negative regulation of the cell cycle transition. Promotes pituitary gonadotrope cell proliferation, migration and invasion, when overexpressed. May play a role in cell pituitary tumor development.|||Mitochondrion|||Secreted|||Up-regulated upon differentiation into neuronal cells in the presence of retinoic acid and BDNF. Down-regulated upon differentiation into astroglial cells. Down-regulated in gonadotrope cells by bone morphogenetic protein and retinoic acid. http://togogenome.org/gene/10090:Pcdhga4 ^@ http://purl.uniprot.org/uniprot/Q91XY4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Cell membrane|||Expressed in stage P0-P2 spinal astrocytes, stage P15 hippocampus where expression is detected in some pyramidal neurons, and stage P18 cerebellum where strong expression is detected in a few scattered Purkinje cells and weak expression in neighboring Purkinje cells.|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain (By similarity). http://togogenome.org/gene/10090:Gjb3 ^@ http://purl.uniprot.org/uniprot/A0A654ICX2|||http://purl.uniprot.org/uniprot/P28231 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins.|||A connexon is composed of a hexamer of connexins. Interacts with CNST.|||Belongs to the connexin family.|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Sst ^@ http://purl.uniprot.org/uniprot/P60041|||http://purl.uniprot.org/uniprot/Q545V6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatostatin family.|||C-terminal amidation of the neuronostatin peptide is required for its biological activity, including for the regulation of mean arterial pressure.|||In the pancreas, somatostatin is expressed in delta cells of the islets of Langerhans. In the stomach, it is expressed in parietal cells of oxyntic mucosa and in the small intestine, it is found in the villus (at protein level) (PubMed:18753129). Neuronostatin is expressed in the pancreas in delta cells of the islets of Langerhans, as well as in the stomach, in parietal cells of oxyntic mucosa and in the small intestine, in the villus (at protein level) (PubMed:18753129).|||Inhibits the secretion of pituitary hormones, including that of growth hormone/somatotropin (GH1), PRL, ACTH, luteinizing hormone (LH) and TSH. Also impairs ghrelin- and GnRH-stimulated secretion of GH1 and LH; the inhibition of ghrelin-stimulated secretion of GH1 can be further increased by neuronostatin.|||May enhance low-glucose-induced glucagon release by pancreatic alpha cells (PubMed:24735892). This effect may be mediated by binding to GPR107 and PKA activation (PubMed:26561648). May regulate cardiac contractile function (PubMed:25012062). May compromise cardiomyocyte viability (By similarity). In the central nervous system, may impair memory retention and may affect hippocampal excitability (By similarity). May also have anxiolytic and anorexigenic effects (By similarity). May play a role in arterial pressure regulation (By similarity). May inhibit basal, but not ghrelin- or GnRH-stimulated secretion of GH1 or LH, but does not affect the release of other pituitary hormones, including PRL, ACTH, FSH or TSH (By similarity). Potentiates inhibitory action of somatostatin on ghrelin-stimulated secretion of GH1, but not that on GnRH-stimulated secretion of LH (By similarity).|||Secreted http://togogenome.org/gene/10090:Cldn34c1 ^@ http://purl.uniprot.org/uniprot/Q8CCR8|||http://purl.uniprot.org/uniprot/Q8K193 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Ifna7 ^@ http://purl.uniprot.org/uniprot/Q810G6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Slc25a21 ^@ http://purl.uniprot.org/uniprot/B6CI26|||http://purl.uniprot.org/uniprot/Q3TRZ4|||http://purl.uniprot.org/uniprot/Q8BZ09 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Membrane|||Mitochondrion inner membrane|||Transports dicarboxylates across the inner membranes of mitochondria by a counter-exchange mechanism. Can transport 2-oxoadipate (2-oxohexanedioate), 2-oxoglutarate, adipate (hexanedioate), glutarate, and to a lesser extent, pimelate (heptanedioate), 2-oxopimelate (2-oxoheptanedioate), 2-aminoadipate (2-aminohexanedioate), oxaloacetate, and citrate. Plays a central role in catabolism of lysine, hydroxylysine, and tryptophan, by transporting common metabolite intermediates (such as 2-oxoadipate) into the mitochondria, where it is converted into acetyl-CoA and can enter the citric acid (TCA) cycle. http://togogenome.org/gene/10090:Stk35 ^@ http://purl.uniprot.org/uniprot/Q80ZW0 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cytoplasm|||Interacts with PDLIM1/CLP-36.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Derl2 ^@ http://purl.uniprot.org/uniprot/Q3U957|||http://purl.uniprot.org/uniprot/Q8BNI4 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the derlin family.|||Endoplasmic reticulum membrane|||Forms homo- and heterooligomers with DERL3 and, to a lesser extent, with DERL1 (By similarity). Interacts with the SEL1L/SYVN1 and VCP/SELENOS protein complexes (PubMed:22016385). Mediates association between VCP and EDEM1, as well as that between VCP and the misfolded glycoproteins (By similarity). Interacts with OS9 (By similarity). Interacts with SELENOK and SELENOS (PubMed:22016385). Interacts with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control (By similarity). Interacts with CCDC47 (PubMed:25009997).|||Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins. May act by forming a channel that allows the retrotranslocation of misfolded glycoproteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and misfolded glycoproteins. May also be involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation.|||Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Up-regulated in response to endoplasmic reticulum stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR).|||Widely expressed, with lowest levels in brain and heart. http://togogenome.org/gene/10090:Cfhr4 ^@ http://purl.uniprot.org/uniprot/B2RUG5|||http://purl.uniprot.org/uniprot/E9Q8B5|||http://purl.uniprot.org/uniprot/E9Q8B6|||http://purl.uniprot.org/uniprot/Q0KHD2|||http://purl.uniprot.org/uniprot/Q0KHD3 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Sult3a2 ^@ http://purl.uniprot.org/uniprot/G5E904 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Jam2 ^@ http://purl.uniprot.org/uniprot/Q9JI59 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily.|||Cell junction|||Cell membrane|||Expressed by bone marrow stromal cells (at protein level) (PubMed:21868569). Expressed in skin (at protein level) (PubMed:16297198). Expressed in testis by Sertoli cells (at protein level) (PubMed:15372036, PubMed:25817991). Expressed by dorsal root ganglion and spinal cord neurons (PubMed:27499083).|||Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate different cellular processes (PubMed:16093349, PubMed:21868569, PubMed:24357068). Plays a role in homing and mobilization of hematopoietic stem and progenitor cells within the bone marrow (PubMed:21868569, PubMed:24357068). At the surface of bone marrow stromal cells, it contributes to the retention of the hematopoietic stem and progenitor cells expressing JAM3 (PubMed:21868569, PubMed:24357068). Plays a central role in leukocytes extravasation by facilitating not only transmigration but also tethering and rolling of leukocytes along the endothelium (PubMed:16297198, PubMed:19740376). Tethering and rolling of leukocytes are dependent on the binding by JAM2 of the integrin alpha-4/beta-1 (PubMed:19740376). Plays a role in spermatogenesis where JAM2 and JAM3, which are respectively expressed by Sertoli and germ cells, mediate an interaction between both cell types and play an essential role in the anchorage of germ cells onto Sertoli cells and the assembly of cell polarity complexes during spermatid differentiation (Probable). Also functions as an inhibitory somatodendritic cue that prevents the myelination of non-axonal parts of neurons (PubMed:27499083). During myogenesis, it is involved in myocyte fusion (By similarity). May also play a role in angiogenesis (PubMed:25911611).|||Mice lacking Jam2 do not display overt morphological, vascular or immunologic phenotype (PubMed:21868569). However, aberrant myelination of dorsal horn interneuron cell bodies is observed (PubMed:27499083, PubMed:21868569). They develop age-dependent significant walking and gait abnormalities compared to controls. Neuropathologic brain analysis show age-dependent progressive prominent vacuolization in the midbrain, thalamus, and cerebral and cerebellar cortices. These changes are associated with reactive astrogliosis, microglial activation, and a reduced neuronal density. Similar findings are observed in spinal cord sections. There is no evidence of mineralization or calcification in the brain or spinal cord of mutant mice (PubMed:32142645).|||The Ig-like V-type domain is necessary and sufficient to mediate interaction with JAM3 and integrin alpha-4/beta-1.|||The expression in Sertoli cells is regulated by TGFB3 through ubiquitin-mediated proteasomal degradation.|||tight junction http://togogenome.org/gene/10090:Mrgprb8 ^@ http://purl.uniprot.org/uniprot/Q7TN51 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Membrane|||Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Smad2 ^@ http://purl.uniprot.org/uniprot/Q62432 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity.|||Belongs to the dwarfin/SMAD family.|||Cytoplasm|||In response to TGF-beta, phosphorylated on the C-terminal SXS motif by TGF-beta and activin type 1 receptor kinases, phosphorylation declines progressively in a KMT5A-dependent manner. Phosphorylation in this motif is required for interaction with a number of proteins including SMURF2, SNON and SMAD4 in response to TGF-beta. Dephosphorylated in this motif by PPM1A leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of the TGF-beta signaling. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin. Phosphorylated by PDPK1.|||In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation. Monoubiquitinated, leading to prevent DNA-binding (PubMed:15496141). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (By similarity). Ubiquitinated by RNF111, leading to its degradation: only SMAD2 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD2 and regulating its turnover (PubMed:17341133).|||Monomer; in the absence of TGF-beta (By similarity). Heterodimer; in the presence of TGF-beta (By similarity). Forms a heterodimer with co-SMAD, SMAD4, in the nucleus to form the transactivation complex SMAD2/SMAD4 (PubMed:21145499). Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta (By similarity). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (By similarity). Interacts (via the MH2 domain) with ZFYVE9; may form trimers with the SMAD4 co-SMAD (PubMed:15356634). Interacts with TAZ/WWRT1 (By similarity). Interacts with FOXH1 (By similarity). Interacts with SNW1 (By similarity). Interacts with CREB-binding protein (CBP) and EP300 (By similarity). Interacts with SNON (By similarity). Interacts with ALK4/ACVR1B (By similarity). Interacts with SKOR1 (By similarity). Interacts with SKOR2 (By similarity). Interacts with PRDM16 (By similarity). Interacts (via MH2 domain) with LEMD3 (By similarity). Interacts with RBPMS (By similarity). Interacts with WWP1. Interacts (dephosphorylated form, via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling (By similarity). Interacts with PDPK1 (via PH domain) (By similarity). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation (By similarity). Interacts with USP15 (By similarity). Interacts with PPP5C (PubMed:22781750). Interacts with LDLRAD4 (via the SMAD interaction motif) (By similarity). Interacts (via MH2 domain) with PMEPA1 (via the SMAD interaction motif) (By similarity). Interacts with ZFHX3 (By similarity). Interacts with ZNF451 (By similarity). Interacts with SMURF2 when phosphorylated on Ser-465/467 (By similarity). Interacts with PPM1A (By similarity). Interacts with TGF-beta (By similarity). Interacts with TGFBR1 (By similarity). Interacts with TGIF (By similarity). Interacts with SMAD3 and TRIM33 (By similarity). Interacts with ZNF580 (By similarity). Interacts with NEDD4L in response to TGF-beta (PubMed:15496141). Interacts with HGS (PubMed:11094085). Interacts with AIP1 (PubMed:10681527). Interacts with WWP1 (PubMed:15221015). Interacts with PML (PubMed:15356634). Interacts weakly with ZNF8 (PubMed:12370310). Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD2 inhibitors (PubMed:17341133). Interacts with YAP1 (when phosphorylated at 'Ser-112') (PubMed:21145499). Interacts when phosphorylated with IPO7; the interaction facilitates translocation of SMAD2 to the nucleus (PubMed:33548622).|||Nucleus|||Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells (PubMed:33548622). Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity). http://togogenome.org/gene/10090:Hspb8 ^@ http://purl.uniprot.org/uniprot/Q9JK92 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small heat shock protein (HSP20) family.|||By progesterone.|||Cytoplasm|||Detected in developing heart throughout embryonic development but only detected in developing liver close to time of birth. In the adult ovary, expression is highest during decidualization and early pregnancy.|||Displays temperature-dependent chaperone activity.|||Highly expressed in skeletal muscle, heart, uterus, liver, lung and ovary. Low levels found in stomach and brain. Not detected in small intestine, large intestine, kidney, spleen and testis. In the ovary, expression is concentrated in the endometrium and in the connective tissue between the circular and longitudinal muscles of the myometrium.|||Monomer. Interacts with HSPB1 (By similarity). Interacts with DNAJB6 (By similarity). Interacts with BAG3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gnptg ^@ http://purl.uniprot.org/uniprot/Q6S5C2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cys-245 mediates the formation of the interchain disulfide bond for formation of the homodimer. Cys-142, Cys-157 and Cys-169 are involved in intramolecular disulfide bonds formation (PubMed:21173149).|||Golgi apparatus|||Homodimer; disulfide-linked. Hexamer of two alpha (GNPTAB), two beta (GNPTAB) and two gamma (GNPTG) subunits; disulfide-linked. The alpha and/or the beta subunits of the enzyme constitute the catalytic subunits (By similarity).|||Non-catalytic subunit of the N-acetylglucosamine-1-phosphotransferase complex, an enzyme that catalyzes the formation of mannose 6-phosphate (M6P) markers on high mannose type oligosaccharides in the Golgi apparatus. Binds and presents the high mannose glycans of the acceptor to the catalytic alpha and beta subunits (GNPTAB). Enhances the rate of N-acetylglucosamine-1-phosphate transfer to the oligosaccharides of acid hydrolase acceptors.|||Secreted|||Widely expressed. Highly expressed in the liver, intestine, brain, thymus, testis and ovary. http://togogenome.org/gene/10090:Bbs7 ^@ http://purl.uniprot.org/uniprot/Q8K2G4 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Due to intron retention.|||May be due to a competing donor splice site.|||Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with BBS2 (via C-terminus). Interacts with CCDC28B. Interacts with SMO; the interaction is indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO.|||The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly (By similarity).|||centriolar satellite|||cilium basal body|||cilium membrane http://togogenome.org/gene/10090:Fam136a ^@ http://purl.uniprot.org/uniprot/Q9CR98 ^@ Similarity ^@ Belongs to the FAM136 family. http://togogenome.org/gene/10090:Fth1 ^@ http://purl.uniprot.org/uniprot/P09528 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 9.5 dpc, detected at low levels in the developing heart and central nervous system. At later stages of development, widely expressed, predominantly in the heart and brown fat tissue.|||Belongs to the ferritin family.|||Cytoplasm|||Homozygous mutant embryos die in utero between 3.5 and 9.5 dpc (PubMed:10652280). Heterozygous animals are healthy and fertile and do not present any apparent abnormalities. They show slightly elevated tissue light chain ferritin content and 7- to 10-fold more light chain ferritin in the serum than normal mice, but their serum iron remains unchanged.|||Oligomer of 24 subunits. There are two types of subunits: L (light) chain and H (heavy) chain. The major chain can be light or heavy, depending on the species and tissue type. The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited.|||Stores iron in a soluble, non-toxic, readily available form (By similarity). Important for iron homeostasis (By similarity). Has ferroxidase activity (By similarity). Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation (By similarity). Also plays a role in delivery of iron to cells (PubMed:19154717). Mediates iron uptake in capsule cells of the developing kidney (PubMed:19154717). http://togogenome.org/gene/10090:Mutyh ^@ http://purl.uniprot.org/uniprot/Q762D1|||http://purl.uniprot.org/uniprot/Q99P21 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adenine glycosylase active on G-A mispairs.|||Belongs to the Nth/MutY family.|||Binds 1 [4Fe-4S] cluster.|||Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand.|||Expressed in heart, lung, liver, intestine, brain and thymus.|||Involved in oxidative DNA damage repair. Initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. Possesses both adenine and 2-OH-A DNA glycosylase activities.|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Lingo3 ^@ http://purl.uniprot.org/uniprot/Q6GQU6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Irak1bp1 ^@ http://purl.uniprot.org/uniprot/G5E885|||http://purl.uniprot.org/uniprot/Q9ESJ7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IRAK1BP1 family.|||Component of the IRAK1-dependent TNFRSF1A signaling pathway that leads to NF-kappa-B activation and is required for cell survival. Acts by enhancing RELA transcriptional activity.|||Cytoplasm|||Expressed in testis, brain, kidney, liver and heart.|||Expression peaks at 10 dpc.|||Interacts with IRAK1 and RELA. Interacts with HSPA8 and HSPA1. May interact with Listeria monocytogenes actA.|||Nucleus|||Phosphorylation at Ser-55, Ser-61 and/or Ser-63 is required for full activity. Phosphorylated on at least one of Ser-234, Thr-236, Ser-241 and Thr-246 upon TNF-alpha activation, which favors nuclear translocation.|||The disordered region interacts with HSPA1 and HSPA8. http://togogenome.org/gene/10090:Tubg2 ^@ http://purl.uniprot.org/uniprot/Q6F4J0|||http://purl.uniprot.org/uniprot/Q8VCK3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tubulin family.|||Phosphorylation at Ser-131 by BRSK1 regulates centrosome duplication, possibly by mediating relocation of gamma-tubulin and its associated proteins from the cytoplasm to the centrosome.|||Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation (By similarity).|||Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.|||centrosome http://togogenome.org/gene/10090:B3gat2 ^@ http://purl.uniprot.org/uniprot/P59270 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 43 family.|||Expressed in brain, but not in liver and kidney.|||Golgi apparatus membrane|||Homodimer.|||Involved in the biosynthesis of L2/HNK-1 carbohydrate epitope on both glycolipids and glycoproteins. http://togogenome.org/gene/10090:Slc25a28 ^@ http://purl.uniprot.org/uniprot/Q8R0Z5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial iron transporter that mediates iron uptake. Probably required for heme synthesis of hemoproteins and Fe-S cluster assembly in non-erythroid cells.|||Mitochondrion inner membrane|||Ubiquitously expressed at low level. Expression does not vary during erythroid maturation. http://togogenome.org/gene/10090:Borcs6 ^@ http://purl.uniprot.org/uniprot/Q9D6W8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor.|||Belongs to the BORCS6 family.|||Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN.|||Lysosome membrane http://togogenome.org/gene/10090:Or1e34 ^@ http://purl.uniprot.org/uniprot/Q8VGR5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rhot2 ^@ http://purl.uniprot.org/uniprot/Q8JZN7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrial Rho GTPase family.|||Interacts with the kinesin-binding proteins TRAK1/OIP106 and TRAK2/GRIF1, forming a link between mitochondria and the trafficking apparatus of the microtubules (By similarity). Interacts with ARMCX3 (PubMed:22569362). Found in a complex with KIF5B, OGT, RHOT1 and TRAK1 (By similarity).|||Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (By similarity).|||Mitochondrion outer membrane|||Ubiquitinated by PRKN in a PINK1-dependent manner, leading to its degradation.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Egr3 ^@ http://purl.uniprot.org/uniprot/P43300|||http://purl.uniprot.org/uniprot/Q3ZB14 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the EGR C2H2-type zinc-finger protein family.|||Nucleus|||Probable transcription factor involved in muscle spindle development. http://togogenome.org/gene/10090:Malt1 ^@ http://purl.uniprot.org/uniprot/Q2TBA3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C14B family.|||Homooligomer; forms oligomers which bind to TRAF6. Forms a complex with CARD14 and MALT1; resulting in the formation of a CBM (CARD14-BCL10-MALT1) complex. Forms a complex with CARD11 and MALT1; resulting in the formation of a CBM (CARD11-BCL10-MALT1) complex (By similarity). Forms a complex with CARD9 and MALT1; resulting in the formation of a CBM (CARD9-BCL10-MALT1) complex (PubMed:22265677).|||Nucleus|||Protease that enhances BCL10-induced activation: acts via formation of CBM complexes that channel adaptive and innate immune signaling downstream of CARD domain-containing proteins (CARD9, CARD11 and CARD14) to activate NF-kappa-B and MAP kinase p38 pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (By similarity). Mediates BCL10 cleavage: MALT1-dependent BCL10 cleavage plays an important role in T-cell antigen receptor-induced integrin adhesion (By similarity). Involved in the induction of T helper 17 cells (Th17) differentiation (By similarity). Cleaves RC3H1 and ZC3H12A in response to T-cell receptor (TCR) stimulation which releases their cooperatively repressed targets to promote Th17 cell differentiation (PubMed:25282160). Also mediates cleavage of N4BP1 in T-cells following TCR-mediated activation, leading to N4BP1 inactivation. May also have ubiquitin ligase activity: binds to TRAF6, inducing TRAF6 oligomerization and activation of its ligase activity (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Ggh ^@ http://purl.uniprot.org/uniprot/Q9Z0L8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C26 family.|||Homodimer.|||Hydrolyzes the polyglutamate sidechains of pteroylpolyglutamates. Progressively removes gamma-glutamyl residues from pteroylpoly-gamma-glutamate to yield pteroyl-alpha-glutamate (folic acid) and free glutamate. May play an important role in the bioavailability of dietary pteroylpolyglutamates and in the metabolism of pteroylpolyglutamates and antifolates.|||Isoform I (more expressed than isoform II in all tissues) is highly expressed in salivary gland, followed by kidney, liver, lung, stomach and uterus, and weakly expressed in small intestine, brain and fetal liver. Also expressed at a lower level in thymus, spleen and skeletal muscle. Also expressed in tumors.|||Lysosome|||Melanosome|||extracellular space http://togogenome.org/gene/10090:Cfl2 ^@ http://purl.uniprot.org/uniprot/P45591|||http://purl.uniprot.org/uniprot/Q3UHW9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the actin-binding proteins ADF family.|||Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods. Required for muscle maintenance. May play a role during the exchange of alpha-actin forms during the early postnatal remodeling of the sarcomere.|||Interacts with CSRP3; possibly two molecules of CFL2 can interact with one molecule if CSRP3.|||Nucleus matrix|||Predominantly expressed in skeletal muscle.|||The phosphorylation of Ser-24 may prevent recognition of the nuclear localization signal.|||cytoskeleton http://togogenome.org/gene/10090:Cers1 ^@ http://purl.uniprot.org/uniprot/A2RT05|||http://purl.uniprot.org/uniprot/P27545 ^@ Activity Regulation|||Disease Annotation|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563).|||Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:12105227, PubMed:16951403, PubMed:17977534, PubMed:18541923, PubMed:30605666). Plays a predominant role in skeletal muscle in regulating C18 ceramide and dihydroceramide levels with an impact on whole-body glucose metabolism and insulin sensitivity. Protects from diet-induced obesity by suppressing the uptake of glucose in multiple organs in a FGF21-dependent way (PubMed:30605666). Generates C18 ceramides in the brain, playing a critical role in cerebellar development and Purkinje cell function (PubMed:21625621). In response to cellular stress mediates mitophagy, a known defense mechanism against cell transformation and aging. Upon mitochondria fission, generates C18 ceramides that anchor lipidated MAP1LC3B/LC3B-II autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria (By similarity).|||Defects in CERS1 cause cerebellar ataxia and Purkinje cell degeneration. Two mouse strains flincher (fln) and toppler (to) carry spontaneous recessive mutations at the TLC domain of CERS1, resulting in complete loss of the catalytic activity associated with a reduction in sphingolipid biosynthesis and accumulation of lipofuscin in many brain regions.|||Endoplasmic reticulum membrane|||Expressed in brain, skeletal muscle, heart and perigonadal white adipose tissue.|||Inhibited by fumonisin B1.|||Membrane|||This protein is produced by a bicistronic gene which also produces the GDF1 protein from a non-overlapping reading frame.|||Up-regulated in skeletal muscle in response to high-fat diet. http://togogenome.org/gene/10090:Spata31d1c ^@ http://purl.uniprot.org/uniprot/E9QAF1|||http://purl.uniprot.org/uniprot/Q3V093 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Nrd1 ^@ http://purl.uniprot.org/uniprot/A6PWC3|||http://purl.uniprot.org/uniprot/Q8BHG1 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M16 family.|||Binds 1 zinc ion per subunit.|||Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs. Is a critical activator of BACE1- and ADAM17-mediated pro-neuregulin ectodomain shedding, involved in the positive regulation of axonal maturation and myelination (PubMed:19935654). Required for proper functioning of 2-oxoglutarate dehydrogenase (OGDH) (PubMed:28017472).|||Highly expressed in brain of early postnatal mice but expressed at a lower level in the brains of adult mice. Expression is high in cortical neurons, and lower in neurons in the striatum. Very low expression detected in the corpus callosum. Also expressed in the gray matter in spinal cord and dorsal root ganglia.|||Interacts with BACE1 and NRG1.|||Knockout mice are born at the expected Mendelian rate, but high lethality is observed within 48 hours from birth. Surviving mice are smaller than wild-type animals, have several neurological defects, impaired motor activity, and deficits of working memory. The cerebral cortex is thin and lateral ventricles are enlarged. The volume and proportion of myelinated axons is markedly reduced in both central and peripheral nervous system.|||Mitochondrion|||dendrite http://togogenome.org/gene/10090:Nasp ^@ http://purl.uniprot.org/uniprot/B1AU75|||http://purl.uniprot.org/uniprot/B1AU76|||http://purl.uniprot.org/uniprot/Q99MD9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NASP family.|||Binds to linker H1 histones but not to core histones (PubMed:10893414, PubMed:12509435). Interacts with histones H2A, H2B, H3 and H4 (By similarity). Interacts with histone H3.3 (By similarity). Also binds to HSP90 in the cytoplasm (PubMed:15533935). This interaction stimulates binding of NASP to H1-6/H1T (PubMed:15533935).|||Cytoplasm|||During the cell cycle, levels increase during S-phase.|||Isoform 1 is found in gametes, embryonic cells and transformed cells. Isoform 2 is found in dividing somatic cells (at protein level).|||Mice develop to blastocyst stage, probably as a result of maternally-derived Nasp, and then die.|||Nucleus|||Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and linker H1 histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. http://togogenome.org/gene/10090:Tdrd7 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQD1|||http://purl.uniprot.org/uniprot/Q8K1H1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, it is expressed in differentiating fiber cells in the posterior lens, but not in the anterior epithelium of the lens (AEL).|||Belongs to the TDRD7 family.|||Component of specific cytoplasmic RNA granules involved in post-transcriptional regulation of specific genes: probably acts by binding to specific mRNAs and regulating their translation. Required for lens transparency during lens development, by regulating translation of genes such as CRYBB3 and HSPB1 in the developing lens. Also required during spermatogenesis.|||Cytoplasm|||Found in a mRNP complex, at least composed of TDRD1, TDRD6, TDRD7 and DDX4. Found in a complex containing CABLES1, CDK16 and CDK17. Interacts with CABLES1, CDK17 and PIWIL1.|||Mainly expressed in testis. Expressed in spermatogonia, spermatocytes and round spermatids (at protein level). Also expressed in the developing lens.|||Mice develop cataracts and glaucoma and males are sterile. Within 4 weeks of birth, mice develop a posterior cataract that becomes severe with age. At later stages, the lens fiber cell compartment develops vacuoles with lens capsule rupture and extrusion of fiber cell mass into the vitreous. In addition, the mass of fiber cells passes through the pupil into the anterior chamber of the eye. By 4 months of age, iris flattening is detected and anterior chamber depth increased. By 6 months of age, the intraocular pressure (IOP) is elevated in some mutants, and the incidence of elevated IOP increases with age, leading to glaucome. Severe optic nerve atrophy characterized by retinal ganglion cell axon loss and excavative remodeling of the optic nerve are observed. In addition, males display sterility due to an arrest in spermatogenesis at the round spermatid stage, likely due to a chromatoid body defect. http://togogenome.org/gene/10090:Txn1 ^@ http://purl.uniprot.org/uniprot/P10639 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).|||Belongs to the thioredoxin family.|||Cytoplasm|||Homodimer; disulfide-linked. Interacts with TXNIP through the redox-active site. Interacts with MAP3K5 and CASP3. Interacts with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA-binding activity in a redox-dependent manner (By similarity).|||In the fully reduced protein, both Cys-69 and Cys-73 are nitrosylated in response to nitric oxide (NO). When two disulfide bonds are present in the protein, only Cys-73 is nitrosylated. Cys-73 can serve as donor for nitrosylation of target proteins (By similarity).|||Nucleus|||Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (By similarity). Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity (By similarity).|||Secreted http://togogenome.org/gene/10090:Ndufs7 ^@ http://purl.uniprot.org/uniprot/Q9DC70 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I 20 kDa subunit family.|||Binds 1 [4Fe-4S] cluster.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits (By similarity). This is a component of the iron-sulfur (IP) fragment of the enzyme (By similarity).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity of complex I.|||Hydroxylated ar Arg-111 by NDUFAF5 early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ctdnep1 ^@ http://purl.uniprot.org/uniprot/Q3TP92 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dullard family.|||Endoplasmic reticulum membrane|||Interacts with CNEP1R1; the complex dephosphorylates LPIN1 and LPIN2.|||Muscle specific with lower expression in other metabolic tissues.|||Nucleus membrane|||Serine/threonine protein phosphatase forming with CNEP1R1 an active phosphatase complex that dephosphorylates and may activate LPIN1 and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol. May antagonize BMP signaling (By similarity). http://togogenome.org/gene/10090:Trim39 ^@ http://purl.uniprot.org/uniprot/Q9ESN2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated.|||Belongs to the TRIM/RBCC family.|||E3 ubiquitin-protein ligase (By similarity). May facilitate apoptosis by inhibiting APC/C-Cdh1-mediated poly-ubiquitination and subsequent proteasome-mediated degradation of the pro-apoptotic protein MOAP1 (By similarity). Regulates the G1/S transition of the cell cycle and DNA damage-induced G2 arrest by stabilizing CDKN1A/p21 (By similarity). Positively regulates CDKN1A/p21 stability by competing with DTL for CDKN1A/p21 binding, therefore disrupting DCX(DTL) E3 ubiquitin ligase complex-mediated CDKN1A/p21 ubiquitination and degradation (By similarity).|||Interacts with MOAP1 (By similarity). Interacts with CDKN1A (By similarity).|||Mitochondrion|||Nucleus|||cytosol http://togogenome.org/gene/10090:Psmg2 ^@ http://purl.uniprot.org/uniprot/Q9EST4 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PSMG2 family.|||Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization (By similarity).|||Degraded by the proteasome upon completion of 20S proteasome maturation.|||Expression is elevated in proliferating cells and down-regulated in cells undergoing growth arrest. During the cell cycle, expression is low in G1-arrested cells, increases during S phase and remains high at G2-M phase.|||Forms a heterodimer with PSMG1. The PSMG1-PSMG2 heterodimer interacts directly with the PSMA5 and PSMA7 proteasome alpha subunits (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ddb1 ^@ http://purl.uniprot.org/uniprot/Q3U1J4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated, promoting interaction with CUL4 (CUL4A or CUL4B) and subsequent formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. Deacetylation by SIRT7 impairs the interaction with CUL4 (CUL4A or CUL4B) and formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes.|||Belongs to the DDB1 family.|||Component of the UV-DDB complex which includes DDB1 and DDB2; the heterodimer dimerizes to give rise to a heterotetramer when bound to damaged DNA. The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit. Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1. DDB1 may recruit specific substrate targeting subunits to the DCX complex. These substrate targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Interacts with AMBRA1, ATG16L1, BTRC, CRBN, DCAF1, DCAF4, DCAF5, DCAF6, DCAF7, DCAF8, DCAF9, DCAF10, DCAF11, DCAF12, DCAF15, DCAF16, DCAF17, DDA1, DET1, DTL, ERCC8, FBXW5, FBXW8, GRWD1, KATNB1, NLE1, NUP43, PAFAH1B1, PHIP, PWP1, RBBP4, RBBP5, RBBP7, COP1, SNRNP40, DCAF1, WDR5, WDR5B, WDR12, WDR26, WDR39, WDR42, WDR53, WDR59, WDR61, WSB1, WSB2, LRWD1 and WDTC1. DCX complexes may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. Interacts with NF2, TSC1 and TSC2. Interacts with AGO1 and AGO2. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Interacts directly with DYRK2. DCX(DTL) complex interacts with FBXO11; does not ubiquitinate and degradate FBXO11. Interacts with TRPC4AP (By similarity). Interacts with CRY1 and CRY2 (PubMed:27123980). The DDB1-CUL4A complex interacts with CRY1 (PubMed:27123980). Component of the DCX(DCAF13) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF13 and RBX1. Interacts with DCAF13 (via WD40 domain) (PubMed:30111536, PubMed:31492966, PubMed:35178836).|||Cytoplasm|||Expressed in germinal vesicle (GV) stage and MII-stage oocytes and zygotes. Expression then decreases from 2-cell stage to blastula (PubMed:24357321). Widely expressed at 8.5 dpc, 9.5 dpc, 12.5 dpc, and 19.5 dpc (PubMed:10574459).|||Mice showed impaired gluconeogenesis in the liver.|||Nucleus|||Phosphorylated by ABL1.|||Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:12107171, PubMed:26431207, PubMed:28790135). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:12107171). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (By similarity). Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (By similarity). DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (By similarity). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (By similarity). DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (By similarity). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication (By similarity). DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR) (By similarity). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver (PubMed:28790135). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (PubMed:24357321). Maternal factor required for proper zygotic genome activation and genome reprogramming (PubMed:24357321).|||The core of the protein consists of three WD40 beta-propeller domains.|||Ubiquitinated by CUL4A. Subsequently degraded by ubiquitin-dependent proteolysis.|||Widely expressed. Expressed in pregnant, lactating and involuting mammary gland. Expressed in oocytes (at protein level) (PubMed:24357321). http://togogenome.org/gene/10090:Usp17la ^@ http://purl.uniprot.org/uniprot/Q61068 ^@ Function|||Induction|||PTM|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes. Has deubiquitinating enzyme activity for DNAH5, suggesting a role in the regulation of DNAH5 degradation by the ubiquitin-proteasome pathway. Has growth-suppressing activity; induces arrest in G1 phase upon controlled expression.|||Expressed in hematopoietic progenitor cell lines Ba/F3 and FDCP1. Not detected in brain, lung, liver, kidney, thymus, spleen and bone marrow.|||Polyubiquitinated; ubiquitination leads to its subsequent degradation.|||Up-regulated by IL3, IL5 and CSF2. http://togogenome.org/gene/10090:Mesp1 ^@ http://purl.uniprot.org/uniprot/P97309 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression is induced by Notch signaling.|||Mice embryos exhibit defects in single heart tube formation, due to a delay in mesodermal migration. However, the cells eventually acquired migratory activity and gave rise to an abnormal heart tube. Mice lacking Mesp1 and Mesp2 die around 9.5 dpc. The major defect is the apparent lack of any mesodermal layer between endoderm and ectoderm and a defect in the migratory activity of mesodermal cells. It seems that a compensatory mechanism exists in which Mesp1 expression is up-regulated in the absence of Mesp2. Mesp1 may be involved in the rescue of somitogenesis in the null Mesp2 embryos.|||No expression was detected in adult tissues except the testis. Expression in the testis was regulated developmentally; expressed 2 weeks after birth, and increases, reaching the full expression level in mature testes.|||Nucleus|||The earliest expression is detected at the junction of the epiblast and extraembryonic ectoderm, which is the initiation site for gastrulation. Around 6.5-6.75 dpc, expression becomes evident as gastrulation progresses. Expression does not spread over all mesodermal cells; it is seen only in a fraction of cells, particularly those in the early emergence group destined to become the extraembryonic mesoderm and the most posterior part of the tailbud. Expression remains for a while at the base of the allantois, and then spreads out to the lateral margins of the tail bud mesoderm. Expressed in the anterior presomitic mesoderm in a broad or thin stripe pattern. Expressed in the paraxial mesoderm during somitogenesis. Expression disappears before 8.5 dpc.|||Transcription factor. Plays a role in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm. Defines the rostrocaudal patterning of the somites by participating in distinct Notch pathways. http://togogenome.org/gene/10090:Gatm ^@ http://purl.uniprot.org/uniprot/Q9D964 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amidinotransferase family.|||Expressed in a wide range of extraembryonic and embryonic tissues throughout development. Expressed at relatively low levels in mid-gestation stage embryos, with expression gradually increasing during embryonic development.|||Expressed in kidney, brain, gonads, uterus, and embryonic head, chest and abdomen. Maternally expressed in the placenta and yolk sac of embryos.|||Homodimer.|||Knockout mice do not manifest aminoaciduria or glucosuria.|||Mitochondrion inner membrane|||Transamidinase that catalyzes the transfer of the amidino group of L-arginine onto the amino moiety of acceptor metabolites such as glycine, beta-alanine, gamma-aminobutyric acid (GABA) and taurine yielding the corresponding guanidine derivatives (By similarity). Catalyzes the rate-limiting step of creatine biosynthesis, namely the transfer of the amidino group from L-arginine to glycine to generate guanidinoacetate, which is then methylated by GAMT to form creatine. Provides creatine as a source for ATP generation in tissues with high energy demands, in particular skeletal muscle, heart and brain (By similarity). http://togogenome.org/gene/10090:Clec18a ^@ http://purl.uniprot.org/uniprot/Q7TSQ1 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:As3mt ^@ http://purl.uniprot.org/uniprot/Q91WU5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methyltransferase superfamily. Arsenite methyltransferase family.|||Catalyzes the transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals. It methylates arsenite to form methylarsonate, Me-AsO(3)H(2), which is reduced by methylarsonate reductase to methylarsonite, Me-As(OH)2. Methylarsonite is also a substrate and it is converted into the much less toxic compound dimethylarsinate (cacodylate), Me(2)As(O)-OH.|||cytosol http://togogenome.org/gene/10090:Sp1 ^@ http://purl.uniprot.org/uniprot/O89090 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts with murine minute virus NS1; this interaction allows high levels of viral P38 promoter transactivation by NS1.|||Acetylated. Acetylation/deacetylation events affect transcriptional activity. Deacetylation leads to an increase in the expression the 12(s)-lipooxygenase gene though recruitment of p300 to the promoter (By similarity).|||Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Cytoplasm|||Interacts with ATF7IP, ATF7IP2, BAHD1, POGZ, HCFC1, AATF and PHC2. Interacts with SV40 VP2/3 proteins. Interacts with SV40 major capsid protein VP1; this interaction leads to a cooperativity between the 2 proteins in DNA binding. Interacts with HLTF; the interaction may be required for basal transcriptional activity of HLTF. Interacts (deacetylated form) with EP300; the interaction enhances gene expression. Interacts with HDAC1 and JUN. Interacts with ELF1; the interaction is inhibited by glycosylation of SP1. Interaction with NFYA; the interaction is inhibited by glycosylation of SP1. Interacts with SMARCA4/BRG1. Interacts with ATF7IP and TBP. Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a. Interacts with EGR1 (By similarity). Interacts with RNF112 in an oxidative stress-regulated manner (PubMed:27918959). Interacts with ZBTB7A; ZBTB7A prevents the binding to GC-rich motifs in promoters and represses the transcriptional activity of SP1 (By similarity). Interacts with DDX3X; this interaction potentiates SP1-induced CDKN1A/WAF1/CIP1 transcription (By similarity). Interacts with MSX1; the interaction may inhibit MSX1 autoinactivation (PubMed:10215616). Interacts with MSX3 (PubMed:10215616).|||Nucleus|||O-glycosylated; Contains 8 N-acetylglucosamine side chains. Levels are controlled by insulin and the SP1 phosphorylation states. Insulin-mediated O-glycosylation locates SP1 to the nucleus, where it is sequentially deglycosylated and phosphorylated. O-glycosylation affects transcriptional activity through disrupting the interaction with a number of transcription factors including ELF1 and NFYA. Inhibited by peroxisomome proliferator receptor gamma (PPARgamma) (By similarity).|||Phosphorylated on multiple serine and threonine residues. Phosphorylation is coupled to ubiquitination, sumoylation and proteolytic processing. Phosphorylation on Ser-61 enhances proteolytic cleavage. Phosphorylation on Ser-7 enhances ubiquitination and protein degradation. Hyperphosphorylation on Ser-103 in response to DNA damage has no effect on transcriptional activity. MAPK1/MAPK3-mediated phosphorylation on Thr-455 and Thr-738 enhances VEGF transcription but, represses FGF2-triggered PDGFR-alpha transcription. Also implicated in the repression of RECK by ERBB2. Hyperphosphorylated on Thr-280 and Thr-738 during mitosis by MAPK8 shielding SP1 from degradation by the ubiquitin-dependent pathway. Phosphorylated in the zinc-finger domain by calmodulin-activated PKCzeta. Phosphorylation on Ser-642 by PKCzeta is critical for TSA-activated LHR gene expression through release of its repressor, p107. Phosphorylation on Thr-669, Ser-671 and Thr-682 is stimulated by angiotensin II via the AT1 receptor inducing increased binding to the PDGF-D promoter. This phosphorylation is increased in injured artey wall. Ser-61 and Thr-682 can both be dephosphorylated by PP2A during cell-cycle interphase. Dephosphorylation on Ser-61 leads to increased chromatin association during interphase and increases the transcriptional activity. On insulin stimulation, sequentially glycosylated and phosphorylated on several C-terminal serine and threonine residues (By similarity).|||Proteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation (By similarity).|||Sumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation (By similarity).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter Plays an essential role in the regulation of FE65 gene expression (By similarity). Positively regulates the transcription of the core clock component BMAL1 (PubMed:24030830). Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (PubMed:27918959).|||Ubiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation (By similarity).|||Up-regulated by traumatic brain injury and hydrogen peroxide (at protein level)(PubMed:27918959). http://togogenome.org/gene/10090:Wnt16 ^@ http://purl.uniprot.org/uniprot/Q8BRT3|||http://purl.uniprot.org/uniprot/Q8C6P4|||http://purl.uniprot.org/uniprot/Q9QYS1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Wnt family.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity).|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||extracellular matrix http://togogenome.org/gene/10090:Fubp1 ^@ http://purl.uniprot.org/uniprot/Q3TUE1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Sdsl ^@ http://purl.uniprot.org/uniprot/Q8R238 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Abundantly expressed in liver.|||Belongs to the serine/threonine dehydratase family.|||Has low serine dehydratase and threonine dehydratase activity.|||Homodimer. http://togogenome.org/gene/10090:Erc2 ^@ http://purl.uniprot.org/uniprot/Q3UHT7|||http://purl.uniprot.org/uniprot/Q6PH08 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Due to intron retention.|||Expressed throughout the central nervous system, including hippocampus, cortex, cerebellum and olfactory bulb.|||Interacts with BSN, ERC1, PPFIA1, PPFIA2, PPFIA3 and PPFIA4. Interacts through its C-terminus with the PDZ domain of RIMS1. Part of a complex consisting of ERC2, RIMS1 and UNC13A.|||Presynaptic active zone|||Synapse|||Thought to be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. Seems to act together with BSN. May recruit liprin-alpha proteins to the CAZ.|||cytoskeleton http://togogenome.org/gene/10090:Lmo1 ^@ http://purl.uniprot.org/uniprot/Q924W9 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the brain and not in the thymus.|||May be involved in gene regulation within neural lineage cells potentially by direct DNA binding or by binding to other transcription factors.|||Nucleus http://togogenome.org/gene/10090:Celf1 ^@ http://purl.uniprot.org/uniprot/P28659 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with polysomes (By similarity). Interacts with HNRNPH1; the interaction in RNA-dependent. Interacts with PARN (By similarity). Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5.|||Belongs to the CELF/BRUNOL family.|||Cytoplasm|||Expressed in heart, muscle, brain, liver, thigh, stomach and lung at 14 dpc (at protein level). Expressed from the two-cell to blastocyst stages. Expressed in tail region, somites, cephalic structures and limb buds at 10.5 dpc.|||Expressed in skeletal muscle, uterus, diaphragm, lung, spleen, testis, mammary gland, adipose, eye and brain (at protein level). Strongly expressed in aging liver (at protein level). Expressed in lung, stomach, heart to very low levels (at protein level). Expressed in germ cells of the seminiferous tubules except in the central region that contains the elongated spermatids and spermatozoa (at protein level). Expressed in Leydig cells of the interstitial tissue (at protein level). Expressed in the heart, skeletal muscle, testis (from spermatogonia to round spermatids), spleen, lung, neocortex, cerebellar cortex, hippocampus and other areas, abundant in the putamen, and poorly expressed in the thalamus and in the brain stem.|||Its RNA-binding activity on CEBPB mRNA increases in response to EGF.|||Nucleus|||Phosphorylated. Phosphorylated by CDK4 on Ser-302. Its phosphorylation status increases in aging liver and is important for the formation of the EIF2 complex and activation of CEBPB mRNA translation. Hyperphosphorylated in the EIF2 complex. EGFR signaling regulates its phosphorylation status in epithelial cells.|||RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing (By similarity). Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition (By similarity). Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs (By similarity). Activates SM exon 5 inclusion by antagonizing the repressive effect of PTB (By similarity). Promotes exclusion of exon 11 of the INSR pre-mRNA (By similarity). Inhibits, together with HNRNPH1, insulin receptor (IR) pre-mRNA exon 11 inclusion in myoblast (By similarity). Increases translation and controls the choice of translation initiation codon of CEBPB mRNA (By similarity). Increases mRNA translation of CEBPB in aging liver. Increases translation of CDKN1A mRNA by antagonizing the repressive effect of CALR3 (By similarity). Mediates rapid cytoplasmic mRNA deadenylation (By similarity). Recruits the deadenylase PARN to the poly(A) tail of EDEN-containing mRNAs to promote their deadenylation (By similarity). Required for completion of spermatogenesis. Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK and to Bruno response elements (BREs) (By similarity). Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA (By similarity). Binds to AU-rich sequences (AREs or EDEN-like) localized in the 3'-UTR of JUN and FOS mRNAs. Binds to the IR RNA (By similarity). Binds to the 5'-region of CDKN1A and CEBPB mRNAs (By similarity). Binds with the 5'-region of CEBPB mRNA in aging liver. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF2, negatively regulates the processing to mature miRNA (By similarity).|||RRM1 and RRM2 domains preferentially target UGU(U/G)-rich mRNA elements. http://togogenome.org/gene/10090:Or52d1 ^@ http://purl.uniprot.org/uniprot/Q8VGW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sec16a ^@ http://purl.uniprot.org/uniprot/E9QAT4|||http://purl.uniprot.org/uniprot/Q8K000 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17428803). Mediates the recruitment of MIA3/TANGO to ERES. Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (By similarity). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in adipocytes (PubMed:27354378).|||Belongs to the SEC16 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Microsome membrane|||SEC16A and SEC16B are each present in multiple copies in a heteromeric complex (By similarity). Interacts with SEC23A (PubMed:17428803). Interacts with RNF183, RNF152, MIA3 and SEC13 (By similarity). Interacts with GORASP2 in response to ER stress (By similarity). Interacts with LRRK2 (via ROC domain) (PubMed:25201882). Interacts with RAB10 (PubMed:27354378).|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Ms4a5 ^@ http://purl.uniprot.org/uniprot/Q810P8 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Syf2 ^@ http://purl.uniprot.org/uniprot/Q9D198 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the heart, liver and kidney. Expressed at lower level other tissues.|||Belongs to the SYF2 family.|||Identified in the spliceosome C complex. Interacts with CCNDBP1.|||Involved in pre-mRNA splicing as component of the spliceosome.|||Nucleus http://togogenome.org/gene/10090:Chd8 ^@ http://purl.uniprot.org/uniprot/Q09XV5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily.|||DNA helicase that acts as a chromatin remodeling factor and regulates transcription. Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. Involved in both enhancer blocking and epigenetic remodeling at chromatin boundary via its interaction with CTCF. Acts as a suppressor of STAT3 activity by suppressing the LIF-induced STAT3 transcriptional activity. Also acts as a transcription activator via its interaction with ZNF143 by participating in efficient U6 RNA polymerase III transcription. Regulates alternative splicing of a core group of genes involved in neuronal differentiation, cell cycle and DNA repair. Enables H3K36me3-coupled transcription elongation and co-transcriptional RNA processing likely via interaction with HNRNPL.|||Death during early embryogenesis due to widespread apoptosis. Embryos manifest growth retardation from 5.5 dpc and developmental arrest accompanied by massive apoptosis at 7.5 dpc. They develop into an egg cylinder but do not form a primitive streak or mesoderm. Mice lacking both Tp53 and Chd8 ameliorate this developmental arrest.|||Expressed predominantly from early- to mid-stage mouse embryogenesis. Detected throughout embryos from 7.5 to 9.5 dpc but localizes predominantly in the brain, faces, branchial arches, limb buds, and tail buds of embryos at 10.5 dpc.|||Interacts with CTNNB1 and PIAS3. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with CHD7. Interacts with FAM124B (By similarity). Interacts with p53/TP53 and histone H1 (PubMed:19151705). Interacts with CTCF (PubMed:16949368). Interacts with TLK2 (By similarity). Interacts with HNRNPL in an RNA-dependent manner.|||Nucleus|||Partially unspliced pre-RNA.|||Sumoylated. http://togogenome.org/gene/10090:Or9a2 ^@ http://purl.uniprot.org/uniprot/Q924H8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mylk3 ^@ http://purl.uniprot.org/uniprot/Q3UIZ8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Kinase that phosphorylates MYL2 in vitro (PubMed:18202317, PubMed:17885681). Has been proposed to be calmodulin-dependent (PubMed:17885681), although MYL2 phosphorylation has also been observed in the presence or absence of calmodulin (PubMed:18202317). Promotes sarcomere formation in cardiomyocytes and increases cardiomyocyte contractility (By similarity).|||Phosphorylated on serine residues.|||Restricted to cardiomyocytes (at protein level). Down-regulated in heart after experimental myocardial infarction at the protein level; no significant changes at the mRNA level.|||Up-regulated in the heart from 10.5 dpc to neonates and further increased in adults. Down-regulated in aged hearts (at protein level). http://togogenome.org/gene/10090:Arhgef7 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0X8|||http://purl.uniprot.org/uniprot/Q9ES28 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a RAC1 guanine nucleotide exchange factor (GEF) and can induce membrane ruffling. May function as a positive regulator of apoptosis. Functions in cell migration, attachment and cell spreading. Promotes targeting of RAC1 to focal adhesions. Downstream of NMDA receptors and CaMKK-CaMK1 signaling cascade, promotes the formation of spines and synapses in hippocampal neurons (By similarity).|||Interacts with PAK kinases through the SH3 domain. Interacts with unphosphorylated PAK1. Interacts with ITCH. Interacts with SCRIB; interaction is direct and may play a role in regulation of apoptosis (By similarity). Interacts with GIT1 and TGFB1I1. Interacts with FRMPD4 (via N-terminus). Interacts with CaMK1. Interacts with BIN2 (By similarity). Interacts with PTK2/FAK1 and RAC1. Interacts with PARVB. Interacts with YWHAZ (PubMed:16959763).|||Phosphorylated on Ser-673 by CaMK1; enhancement of GEF activity and downstream activation of RAC1 (By similarity). Phosphorylated by PTK2/FAK1; this promotes interaction with RAC1.|||Produced by alternative initiation at Met-158 of isoform G.|||Seems to be expressed in the central nervous system. Isoform B, isoform C and isoform E are expressed with highest levels in brain and testis.|||cell cortex|||focal adhesion|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Or14j4 ^@ http://purl.uniprot.org/uniprot/B2RTB9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Arhgef10l ^@ http://purl.uniprot.org/uniprot/A2AWP8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC.|||Cytoplasm|||Interacts with RHOA, RHOB and RHOC. http://togogenome.org/gene/10090:Mcf2l ^@ http://purl.uniprot.org/uniprot/E9PXE2|||http://purl.uniprot.org/uniprot/E9PY12|||http://purl.uniprot.org/uniprot/E9PY13|||http://purl.uniprot.org/uniprot/Q6PDM6 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Krtap5-2 ^@ http://purl.uniprot.org/uniprot/Q9D5Z7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 5 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Stim1 ^@ http://purl.uniprot.org/uniprot/P70302 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Endoplasmic reticulum membrane|||Expressed in maturation-stage ameloblasts (at protein level). Expressed in all tissues examined and in many cell types, including bone marrow stroma, fibroblast, B-cell precursors, lymphoma and erythroleukemia.|||Glycosylation is required for cell surface expression.|||Monomer in the presence of Ca(2+). It oligomerizes in absence of Ca(2+). Forms homooligomers and heterooligomers with STIM2. Interacts (via the transmembrane region and the SOAR/CAD domain) with SPPL3; the interaction promotes the binding of STIM1 to ORAI1. Interacts with ORAI1. Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends. Interacts with CRACR2A/EFCAB4B; the interaction is direct and takes place in absence of Ca(2+). Forms a complex with CRACR2A/EFCAB4B and ORAI1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations. Interacts with SARAF, promoting a slow inactivation of STIM1-dependent SOCE activity, possibly by facilitating the deoligomerization of STIM1 (By similarity). Interacts with EFHB; the interaction takes place upon Ca(2+)-store depletion and inhibits the association with SARAF (By similarity). Interacts with ASPH. Interacts with SLC35G1; intracellular Ca(2+)-dependent. May interact with ATP1A1, ATP2A2, ATP2B1, ATP2B4, KPNB1 and XPO1; through SLC35G1. Interacts with TMEM203. Interacts with STIMATE, promoting STIM1 conformational switch (By similarity). Interacts with TMEM178A (PubMed:26644563). Interacts with CASQ1 (via C-terminal end and preferentially with the monomeric form); this interaction increases in response to a depletion of intracellular Ca(2+), decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) entry (SOCE) activity (By similarity). Interacts with ADCY8 (By similarity).|||Phosphorylated predominantly on Ser residues.|||Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit ORAI1. Involved in enamel formation. Activated following interaction with STIMATE, leading to promote STIM1 conformational switch.|||Sarcoplasmic reticulum|||The STIM1 Orai1-activating region/CRAC-activating domain (SOAR/CAD) mediates interaction with ORAI1 to activate the channel.|||The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.|||cytoskeleton http://togogenome.org/gene/10090:Stt3b ^@ http://purl.uniprot.org/uniprot/A0A0R4J0D3|||http://purl.uniprot.org/uniprot/Q3TDQ1 ^@ Domain|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STT3 family.|||Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (By similarity). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. This subunit contains the active site and the acceptor peptide and donor lipid-linked oligosaccharide (LLO) binding pockets (By similarity). STT3B is present in a small subset of OST complexes and mediates both cotranslational and post-translational N-glycosylation of target proteins: STT3B-containing complexes are required for efficient post-translational glycosylation and while they are less competent than STT3A-containing complexes for cotranslational glycosylation, they have the ability to mediate glycosylation of some nascent sites that are not accessible for STT3A. STT3B-containing complexes also act post-translationally and mediate modification of skipped glycosylation sites in unfolded proteins. Plays a role in ER-associated degradation (ERAD) pathway that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins by mediating N-glycosylation of unfolded proteins, which are then recognized by the ERAD pathway and targeted for degradation (By similarity).|||Component of the oligosaccharyltransferase (OST) complex (By similarity). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (By similarity). OST can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity).|||Despite low primary sequence conservation between eukaryotic catalytic subunits and bacterial and archaeal single subunit OSTs (ssOST), structural comparison revealed several common motifs at spatially equivalent positions, like the DXD motif 1 on the external loop 1 and the DXD motif 2 on the external loop 2 involved in binding of the metal ion cofactor and the carboxamide group of the acceptor asparagine, the conserved Glu residue of the TIXE/SVSE motif on the external loop 5 involved in catalysis, as well as the WWDYG and the DK/MI motifs in the globular domain that define the binding pocket for the +2 Ser/Thr of the acceptor sequon. In bacterial ssOSTs, an Arg residue was found to interact with a negatively charged side chain at the -2 position of the sequon. This Arg is conserved in bacterial enzymes and correlates with an extended sequon requirement (Asp-X-Asn-X-Ser/Thr) for bacterial N-glycosylation.|||Endoplasmic reticulum membrane|||In strains 129, C57BL/10, C57BL/6 and LP Glu-776 correlates with a B6dom1-positive phenotype, Asp-776 is found in resistant strains. The B6dom1 minor histocompatibility antigen (MiHA) is used as a model antigen in studying immunodominance.|||Membrane http://togogenome.org/gene/10090:Nsmce1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0C0|||http://purl.uniprot.org/uniprot/Q9D720 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NSE1 family.|||Component of the SMC5-SMC6 complex which consists at least of SMC5, SMC6, NSMCE2, NSMCE1, NSMCE4A or EID3 and NSMCE3. NSMCE1, NSMCE4A or EID3 and NSMCE3 probably form a subcomplex that bridges the head domains of the SMC5-SMC6 heterodimer. Interacts with NSMCE3.|||Component of the Smc5-Smc6 complex.|||Nucleus|||RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Involved in maintenance of genome integrity, DNA damage response and DNA repair.|||RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Within MAGE-RING ubiquitin ligase complex, MAGE stimulates and specifies ubiquitin ligase activity likely through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. Involved in maintenance of genome integrity, DNA damage response and DNA repair. NSMCE3/MAGEG1 and NSMCE1 ubiquitin ligase are components of SMC5-SMC6 complex and may positively regulate homologous recombination-mediated DNA repair.|||Ubiquitinated.|||telomere http://togogenome.org/gene/10090:2310057M21Rik ^@ http://purl.uniprot.org/uniprot/Q9D2Q3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ ATPase that regulates mitochondrial ABC transporters ABCB7, ABCB8/MITOSUR and ABCB10. Regulates mitochondrial ferric concentration and heme biosynthesis and plays a role in the maintenance of mitochondrial homeostasis and cell survival.|||Cytoplasm|||Homodimer. Interacts with ABCB7, ABCB8/MITOSUR and ABCB10.|||Mitochondrion http://togogenome.org/gene/10090:Tg ^@ http://purl.uniprot.org/uniprot/O08710 ^@ Caution|||Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (By similarity). The synthesis of T3 and T4 involves iodination of selected tyrosine residues of TG/thyroglobulin followed by their oxidative coupling (By similarity). Following TG re-internalization and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone leading to their secretion into the bloodstream (Probable). One dimer produces 7 thyroid hormone molecules (By similarity).|||Belongs to the type-B carboxylesterase/lipase family.|||Congenital goiter (cog) is caused by a hypertrophy of the thyroid gland (goiter). Mice have reduced growth rate, hypothyroidism due to reduced production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), and lack colloid globules, a structure in the thyroid follicle lumen that is enriched in Tg/thyroglobulin.|||Iodinated on tyrosine residues by TPO (By similarity). There are 4 pairs of iodinated tyrosines used for coupling: acceptor Tyr-25 is coupled to donor Tyr-150 or Tyr-235, acceptor Tyr-2572 is coupled to donor Tyr-2539, acceptor Tyr-2764 in monomer 1 is coupled to donor Tyr-2764 in monomer 2 and acceptor Tyr-1310 in monomer 1 is coupled to donor Tyr-109 in monomer 2 (By similarity).|||Monomer (PubMed:12782676). Homodimer (via ChEL region); occurs in the endoplasmic reticulum and is required for export to the Golgi apparatus (PubMed:19276074, PubMed:12782676). Homooligomer; disulfide-linked; stored in this form in the thyroid follicle lumen (By similarity).|||Secreted|||Specifically expressed in the thyroid gland.|||Sulfated tyrosines are desulfated during iodination.|||The cholinesterase-like (ChEL) region is required for dimerization and export from the endoplasmic reticulum.|||The cholinesterase-like (ChEL) region lacks the Ser residue of the catalytic triad suggesting that it has no esterase activity.|||Undergoes sequential proteolysis by cathepsins to release thyroxine (T4) and triiodothyronine (T3) hormones (PubMed:12782676). In the thyroid follicle lumen, cross-linked TG (storage form) is solubilized by limited proteolysis mediated by cathepsins CTSB and/or CTSL (PubMed:12782676). Partially cleaved TG is further processed by CTSK/cathepsin K and/or CTSL resulting in the release of T4 (PubMed:12782676). Following endocytosis, further processing occurs leading to the release of T3 and more T4 hormones (Probable). http://togogenome.org/gene/10090:Adcy3 ^@ http://purl.uniprot.org/uniprot/B8JK56|||http://purl.uniprot.org/uniprot/Q80TY9|||http://purl.uniprot.org/uniprot/Q8VHH7 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by forskolin (PubMed:11055432, PubMed:25329148). After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity (By similarity).|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:9768837, PubMed:11055432, PubMed:25329148). Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis (PubMed:9768837, PubMed:11055432). Required for the perception of odorants (PubMed:11055432). Required for normal sperm motility and normal male fertility (PubMed:15705663). Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet (PubMed:25329148).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.|||Cell membrane|||Cytoplasm|||Detected in the acrosomal region of epididymal spermatozoa, the acrosomal region of round spermatids and in elongating spermatids (PubMed:15705663). Detected in cilia in the olfactory epithelium (at protein level) (PubMed:9768837, PubMed:11055432, PubMed:25908845). Detected in olfactory epithelium neurons (PubMed:11055432). Detected in brain, testis, late pachytene spermatocytes, round spermatids and elongating spermatids (PubMed:15705663).|||Golgi apparatus|||Membrane|||Mutant mice are born at the expected Mendelian rate, but up to 80% of the pups die within 48 hours after birth. Survival is improved by paring down the litter size shortly after birth. Mutant mice are initially smaller than wild-type, but achieve normal size within three months. Mutant mice do not display the normal electrophysiological responses to odorants that stimulate production of cAMP or inositoltrisphosphate (IP3). Likewise, behavorial responses to smells are abolished (PubMed:11055432). In spite of normal mating behavior, they do not produce any offspring (PubMed:11055432, PubMed:15705663). Male mice have strongly reduced fertility due to defects in sperm motility, an increased rate of spontaneous acrosome reactions and an impaired ability to penetrate the oocyte zona (PubMed:15705663).|||N-glycosylated.|||Rapidly phosphorylated after stimulation by odorants or forskolin. Phosphorylation by CaMK2 at Ser-1077 down-regulates enzyme activity.|||Sumoylated (PubMed:25908845). Sumoylation is required for targeting of olfactory cilia.|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.|||cilium http://togogenome.org/gene/10090:Ecscr ^@ http://purl.uniprot.org/uniprot/Q3TZW0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ECSCR family.|||Cell membrane|||Cytoplasm|||Expressed in all tissues examined, highest expression was observed in lung and spleen endothelial cells.|||Interacts with FLNA. Interacts with the 20S proteasome subunit PSMA7.|||May be heavily O-glycosylated.|||Regulates endothelial chemotaxis and tube formation (By similarity). Has a role in angiogenesis and apoptosis via modulation of the actin cytoskeleton and facilitation of proteasomal degradation of the apoptosis inhibitors BIRC3/IAP1 and BIRC2/IAP2. http://togogenome.org/gene/10090:Macroh2a1 ^@ http://purl.uniprot.org/uniprot/Q8CA90|||http://purl.uniprot.org/uniprot/Q9QZQ8 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the histone H2A family.|||Chromosome|||In contrast to isoform 1, does not bind poly-ADP-ribose (By similarity). Represses SOD3 gene expression (PubMed:23022728).|||Interacts with PARP1.|||Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism (PubMed:28991266, PubMed:34887560). Able to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap them (PubMed:28991266). This prevents PARP1 from further addition of ADP-ribose and thus limits the consumption of nuclear NAD(+), allowing the cell to maintain proper NAD(+) levels in both the nucleus and the mitochondria to promote proper mitochondrial respiration (PubMed:28991266). Increases the expression of genes involved in redox metabolism, including SOD3 (PubMed:23022728).|||Major form. The preferential expression of isoform 2 over that of isoform 1 requires the presence of DDX5/DDX17.|||Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin.|||Nucleus|||Preferentially expressed over isoform 2 in the absence of DDX5/DDX17.|||The macro domain specifically binds poly-ADP-ribose (PubMed:28991266, PubMed:34887560). Binds poly-ADP-ribose with lower affinity compared to premetazoan macroH2A1.1 ortholog (PubMed:34887560).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. Interacts with HDAC1 and HDAC2. Interacts with SPOP. Part of a complex consisting of MACROH2A1, CUL3 and SPOP.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (By similarity). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template (By similarity). Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (By similarity). DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling (By similarity). Involved in stable X chromosome inactivation (By similarity). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (By similarity). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16107708).|||Widely expressed, with high levels in testis. Present in liver, kidney and adrenal gland (at protein level). In the liver, present in hepatocytes and at a lesser extent in cells of the bile ducts. In the kidney, expressed in proximal and distal convoluted tubules and in straight proximal tubules. In the adrenal gland, present in inner cells of the cortex and medulla. http://togogenome.org/gene/10090:Dnah10 ^@ http://purl.uniprot.org/uniprot/D3YYQ8 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Cd300lg ^@ http://purl.uniprot.org/uniprot/Q1ERP8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the CD300 family.|||Expressed in monocyte cell lines. Expressed in certain types of endothelial and myeloid lineage cells. Expressed in mesenteric lymph nodes (LNs), spleen, thymus, lung, heart and kidney. Expressed in high endothelial venules (HEVs) in peripheral and mesenteric LNs (at protein level). Highly expressed in heart. Slightly expressed in spleen and thymus. Isoform 5 is expressed preferentially in heart. Isoform 1 is expressed predominantly in kidney and liver.|||Ig-like V-type domain mediates binding to lymphocyte.|||O-glycosylated with sialylated oligosaccharides.|||Receptor which may mediate L-selectin-dependent lymphocyte rollings. Binds SELL in a calcium dependent manner. Binds lymphocyte.|||multivesicular body membrane http://togogenome.org/gene/10090:Csnk1e ^@ http://purl.uniprot.org/uniprot/Q3TYE1|||http://purl.uniprot.org/uniprot/Q9JMK2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Partially dephosphorylated by PPP5C. May be dephosphorylated by PP1.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.|||Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (By similarity). Participates in Wnt signaling (By similarity). Phosphorylates DVL1 (By similarity). Phosphorylates DVL2 (By similarity). Phosphorylates NEDD9/HEF1 (PubMed:29191835). Central component of the circadian clock (PubMed:18400165, PubMed:19414593, PubMed:21930935). In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:18400165, PubMed:19414593, PubMed:21930935). Controls PER1 and PER2 nuclear transport and degradation (PubMed:10848614, PubMed:14701732, PubMed:18400165, PubMed:19414593, PubMed:21930935). Inhibits cytokine-induced granuloytic differentiation (By similarity).|||Cytoplasm|||Down-regulated during granulocytic differentiation. Does not show circadian oscillations.|||Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. Expressed in monocytes and lymphocytes but not in granulocytes.|||Monomer (By similarity). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (PubMed:11779462). Interacts with ANKRD6 (PubMed:12183362). Interacts with PER1 (By similarity). Interacts with DBNDD2, LRP5, LRP6 and SOCS3 (By similarity). Interacts with SNAI1 (via zinc fingers) (By similarity). Interacts with DDX3X; this interaction greatly enhances CSNK1E affinity for ATP and DVL2 phosphorylation, but inhibits DDX3X ATPase/helicase activity. In the presence of RNA, the interaction is decreased (By similarity).|||No visible phenotype. Has no apparent effect on circadian oscillation of protein levels. Mice exhibit a small but significant increase in circadian period length.|||Nucleus|||Phosphorylation leads to a decrease in the catalytic activity. http://togogenome.org/gene/10090:Mms22l ^@ http://purl.uniprot.org/uniprot/B1AUR6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MMS22 family. MMS22L subfamily.|||Chromosome|||Component of the MMS22L-TONSL complex, a complex at least composed of MMS22L and TONSL/NFKBIL2. Interacts with RAD51; interaction is direct.|||Component of the MMS22L-TONSL complex, a complex that promotes homologous recombination-mediated repair of double-strand breaks (DSBs) at stalled or collapsed replication forks. The MMS22L-TONSL complex is required to maintain genome integrity during DNA replication. It mediates the assembly of RAD51 filaments on single-stranded DNA (ssDNA): the MMS22L-TONSL complex is recruited to DSBs following histone replacement by histone chaperones and eviction of the replication protein A complex (RPA/RP-A) from DSBs. Following recruitment to DSBs, the TONSL-MMS22L complex promotes recruitment of RAD51 filaments and subsequent homologous recombination. Within the complex, MMS22L acts by binding ssDNA.|||Degraded by the ubiquitin-proteasome system upon replication stress.|||Nucleus http://togogenome.org/gene/10090:Or10v5 ^@ http://purl.uniprot.org/uniprot/Q8VGJ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mapt ^@ http://purl.uniprot.org/uniprot/P10637|||http://purl.uniprot.org/uniprot/Q3UH19|||http://purl.uniprot.org/uniprot/Q547J4|||http://purl.uniprot.org/uniprot/Q8C5K4 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in neurons and at a lower level in the liver and kidney. Isoform PNS-tau is expressed in the peripheral nervous system while the others are expressed in the central nervous system.|||Interacts with MARK1, MARK2, MARK3 and MARK4 (By similarity). Interacts with SQSTM1 when polyubiquitinated (PubMed:15953362). Interacts with PSMC2 through SQSTM1 (PubMed:15953362). Interacts with FKBP4 (By similarity). Binds to CSNK1D (By similarity). Interacts with SGK1 (By similarity). Interacts with EPM2A; the interaction dephosphorylates MAPT at Ser-369 (By similarity). Interacts with PIN1 (By similarity). Interacts with LRRK2 (By similarity). Interacts with LRP1, leading to endocytosis; this interaction is reduced in the presence of LRPAP1/RAP (By similarity).|||May be involved in the pathogenesis of cytoplasmic inclusions (as Mallory bodies) in livers of mice chronically intoxicated with Griseofulvin or DDC (3,5-diethoxycarbonyl-2,4-dihydrocollidine), a model for human alcoholic hepatitis. Alteration of Tau (abnormal phosphorylation and cross-linking) could contribute to Mallory bodies formation and disturbance of microtubule function in alcoholic liver disease.|||Membrane|||Phosphorylation at various serine and threonine residues in S-P or T-P motifs by proline-directed protein kinases (PDPK1, CDK1, CDK5, GSK3, MAPK) (a few sites per protein in interphase, more in mitosis), and at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1, MARK2, MARK3, MARK4), causing detachment from microtubules, and their disassembly (By similarity). Phosphorylated by PHK. Dephosphorylation at several serine and threonine residues by the serine/threonine phosphatase PPP5C. Phosphorylation at Ser-554 by BRSK1 and BRSK2 in neurons affects ability to bind microtubules and plays a role in neuron polarization. Phosphorylation at Ser-188 by SGK1 mediates microtubule depolymerization and neurite formation in hippocampal neurons (By similarity).|||Polyubiquitinated. Requires functional TRAF6 and may provoke SQSTM1-dependent degradation by the proteasome (By similarity).|||Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by tau localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.|||Secreted|||Shorter forms or low molecular weight tau (lMW-tau) are generally expressed at early development stages and longer forms or high molecular weight tau (hMW-tau) in the adult brain.|||The tau/MAP repeat binds to tubulin. Type I isoforms contain 3 repeats while type II isoforms contain 4 repeats.|||axon|||cytoskeleton|||cytosol|||dendrite http://togogenome.org/gene/10090:Cibar1 ^@ http://purl.uniprot.org/uniprot/A0A8Q0KEJ4|||http://purl.uniprot.org/uniprot/Q8BP22|||http://purl.uniprot.org/uniprot/Z4YJZ2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a positive regulator of ciliary hedgehog signaling (PubMed:29459677). Probable regulator of ciliogenesis involved in limb morphogenesis (PubMed:30395363). In cooperation with CBY1 it is involved in the recruitment and fusion of endosomal vesicles at distal appendages during early stages of ciliogenesis (By similarity). Plays an important role in the mitochondrial function and is essential for maintaining mitochondrial morphology and inner membrane ultrastructure (By similarity). In vitro, can generate membrane curvature through preferential interaction with negatively charged phospholipids such as phosphatidylinositol 4,5-bisphosphate and cardiolipin and hence orchestrate cristae shape (By similarity).|||Belongs to the CIBAR family.|||Cytoplasm|||Expressed in the heart, liver, spleen, lung, kidney, brain and muscle (at protein level) (PubMed:30404948). Strongly expressed throughout the developing limb bud, including the progress zone and the apical ectodermal ridge (PubMed:30395363).|||High and steady expression is observed in the developing limb throughout embryonic stages 11.5-15.5 dpc.|||Homodimer (via BAR-like domain). Heterodimer with FAM92B (via BAR-like domains). Interacts (via BAR-like domain) with CBY1; this interaction is required for targeting FAM92A to centriole and cilium basal body.|||Knockout homozygous mice show uni- or bilateral abnormal bone growth or exostosis on the deltoid tuberosity of the humerus, abnormalities at the left stifle consistent with a tendon calcification, and abnormal digit morphology including polysyndactyly and osteomas on the hind paw metatarsals.|||Mitochondrion inner membrane|||Nucleus|||The BAR-like domain displays limited similarity to other BAR domains.|||centriole|||cilium|||cilium basal body http://togogenome.org/gene/10090:Gla ^@ http://purl.uniprot.org/uniprot/Q3UM38|||http://purl.uniprot.org/uniprot/Q8BGZ6 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 27 family.|||Homodimer.|||Lysosome http://togogenome.org/gene/10090:Asb13 ^@ http://purl.uniprot.org/uniprot/Q8VBX0 ^@ Domain|||Function|||Similarity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Tgfa ^@ http://purl.uniprot.org/uniprot/P48030|||http://purl.uniprot.org/uniprot/Q545E4 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts with the PDZ domains of SDCBP and SNTA1. The interaction with SDCBP, is required for the targeting to the cell surface. In the endoplasmic reticulum, in its immature form (i.e. with a prosegment and lacking full N-glycosylation), interacts with CNIH. In the Golgi apparatus, may form a complex with CNIH and GORASP2. Interacts (via cytoplasmic C-terminal domain) with NKD2 (By similarity). Interacts with MAGI3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.|||extracellular space http://togogenome.org/gene/10090:Pde6c ^@ http://purl.uniprot.org/uniprot/Q91ZQ1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.|||Belongs to the cyclic nucleotide phosphodiesterase family.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Cell membrane|||Composed of two alpha' subunits that are associated with 3 smaller proteins of 11, 13, and 15 kDa. http://togogenome.org/gene/10090:Timm23 ^@ http://purl.uniprot.org/uniprot/Q9CXU4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tim17/Tim22/Tim23 family.|||Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50.|||Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gpr20 ^@ http://purl.uniprot.org/uniprot/Q8BYC4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor with constitutive G(i) signaling activity that activate cyclic AMP.|||Ubiquitous expressed with abundant expression in intestinal tissues. http://togogenome.org/gene/10090:H2ab1 ^@ http://purl.uniprot.org/uniprot/S4R1E0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Fam72a ^@ http://purl.uniprot.org/uniprot/Q8BFZ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM72 family.|||Cytoplasm|||Expressed at high levels in stomach and also in kidney and, at low levels, in heart (at protein level). In the stomach, highly expressed in foveolar cells, parietal cells and chief cells (at protein level). In kidney, expressed in endothelial cells, mesangial and epithelial cells (parietal and visceral epithelium) around glomerulus (at protein level).|||Interacts with UNG.|||May play a role in the regulation of cellular reactive oxygen species metabolism. May participate in cell growth regulation (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Cep290 ^@ http://purl.uniprot.org/uniprot/E9Q9M0|||http://purl.uniprot.org/uniprot/Q6A078 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic vesicle|||Defects in Cep290 are a cause of early-onset retinal degeneration with autosomal recessive inheritance. The rd16 mutant carries a deletion of residues 1599-1897 in the Cep290 protein. Homozygous rd16 mice are characterized by the appearance of white retinal vessels at 1 month of age and large pigment patches at 2 months. Retinal degeneration is apparent as early as postnatal day 19 and progresses with age. The rd16 retina exhibits altered distribution of Rpgr and phototransduction proteins within the photoreceptor cells.|||Expressed in multiple organs during early postnatal development, with highest levels in hindbrain.|||Involved in early and late steps in cilia formation (PubMed:21565611). Its association with CCP110 is required for inhibition of primary cilia formation by CCP110 (By similarity). May play a role in early ciliogenesis in the disappearance of centriolar satellites and in the transition of primary ciliar vesicles (PCVs) to capped ciliary vesicles (CCVs). Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1 (By similarity). Required for the correct localization of ciliary and phototransduction proteins in retinal photoreceptor cells; may play a role in ciliary transport processes (PubMed:16632484). Required for efficient recruitment of RAB8A to primary cilium (By similarity). In the ciliary transition zone is part of the tectonic-like complex (also named B9 complex) which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition (PubMed:21725307). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2, BBS5 and BBS8/TTC8 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating IQCB1/NPHP5 (By similarity). Activates ATF4-mediated transcription (By similarity).|||Knockout mice appear healthy overall with some runting and a retinal degeneration phenotype. During embryonic development, at 16.5 dpc, they show defective midline fusion. Adult animals show a mild foliation defect in the cerebellum.|||Nucleus|||Part of the tectonic-like complex (also named B9 complex) (PubMed:21725307). Interacts with ATF4 via its N-terminal region (By similarity). Associates with the BBSome complex, interacting (via N-terminus) with BBS4 (By similarity). Interacts with IQCB1/NPHP5; IQCB1 and CEP290/NPHP6 are proposed to form a functional NPHP5-6 module localized to the centrosome. Interacts with NPHP4; the interaction likely requires additional interactors (PubMed:21565611). Interacts with ZNF423, FAM161A, CEP162, CEP162, CEP131, TALPID3, CCDC13, CC2D2A, RPGRIP1 (By similarity). Can self-associate (homo- or heteromeric) (By similarity). Interacts with CCP110; required for suppressing cilia formation (By similarity). Interacts with RPGR (PubMed:16632484). Associates (via C-terminus) with microtubules; association to microtubule is reduced in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, in a process that requires p38 MAP kinase signaling (By similarity). Interacts with FAM161A (By similarity). Interacts with PCM1 (PubMed:17705300). Interacts with CCDC66 (By similarity). Interacts with ARMC9 and CSPP1 (By similarity).|||Similar levels from 7 dpc to 17 dpc in whole embryo and brain. In the cerebellum, expressed most strongly in dividing cells of the external granule layer.|||Ubiquitinated. May undergo monoubiquitination; monoubiquitination is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, but does not cause its displacement from centriolar satellites (By similarity).|||centriolar satellite|||centriole|||centrosome|||cilium|||cilium basal body http://togogenome.org/gene/10090:Pygm ^@ http://purl.uniprot.org/uniprot/Q9WUB3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.|||Allosterically regulated through the non-covalent binding of metabolites, being activated by AMP and inhibited by ATP, ADP, and glucose-6-phosphate. The activity is also controlled by post-translational modifications including phosphorylation.|||Belongs to the glycogen phosphorylase family.|||Homodimer. Homotetramer; to form the enzymatically active phosphorylase A.|||Phosphorylation of Ser-15 converts phosphorylase B (unphosphorylated) to phosphorylase A. http://togogenome.org/gene/10090:H2ac8 ^@ http://purl.uniprot.org/uniprot/B2RVF0|||http://purl.uniprot.org/uniprot/C0HKE1|||http://purl.uniprot.org/uniprot/C0HKE2|||http://purl.uniprot.org/uniprot/C0HKE3|||http://purl.uniprot.org/uniprot/C0HKE4|||http://purl.uniprot.org/uniprot/C0HKE5|||http://purl.uniprot.org/uniprot/C0HKE6|||http://purl.uniprot.org/uniprot/C0HKE7|||http://purl.uniprot.org/uniprot/C0HKE8|||http://purl.uniprot.org/uniprot/C0HKE9 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Several sequencing errors.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Rpl37 ^@ http://purl.uniprot.org/uniprot/Q9D823 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL37 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Brd3 ^@ http://purl.uniprot.org/uniprot/Q8K2F0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromatin reader that recognizes and binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors (PubMed:21536911). Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (PubMed:21536911).|||Interacts (via bromo domains) with acetylated lysine residues on the N-terminus of histone H2A, H2B, H3 and H4 (in vitro) (PubMed:21536911). Interacts (via bromo domain 1) with GATA1 acetylated at 'Lys-312' and 'Lys-315' (PubMed:21555453). Interacts (via bromo domain 1) with GATA2 acetylated on lysine residues (PubMed:21555453).|||Nucleus|||The Bromo domains specifically recognize and bind acetylated histones. http://togogenome.org/gene/10090:Dazl ^@ http://purl.uniprot.org/uniprot/Q3TUC3|||http://purl.uniprot.org/uniprot/Q64368 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM DAZ family.|||Cytoplasm|||Expressed predominantly in testis with lower levels in ovary. In testis, it is expressed in pachytene spermatocytes and at lower level in type-B spermatogonia, preleptotene and zygotene spermatocytes. In ovary, it is expressed in maturing follicles. In embryonic and prepuberal ovary, it is expressed in the oocyte and follicular cells.|||Homodimer and heterodimer. Forms a heterodimer with DAZ. Interacts with BOLL, DAZAP1 and DAZAP2. Interacts with PUM2 (By similarity). Multiple DAZL RRMs can bind to a single RNA containing multiple GUU triplets.|||In the testis, expression increases steadily after birth until the first spermatogonial cells appear, levels off as the first spermatogenic cells enter meiosis (10 days after birth) and remains at this level thereafter.|||RNA-binding protein, which is essential for gametogenesis in both males and females. Plays a central role during spermatogenesis. Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU triplets, and thereby regulating the translation of key transcripts.|||The DAZ domain mediates the interaction with DAZAP1 and DAZAP2. http://togogenome.org/gene/10090:Taf7l2 ^@ http://purl.uniprot.org/uniprot/Q3V063 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TAF7 family.|||Nucleus http://togogenome.org/gene/10090:Or1q1 ^@ http://purl.uniprot.org/uniprot/Q8VFP4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Thap3 ^@ http://purl.uniprot.org/uniprot/Q8BJ25 ^@ Function|||Subunit|||Tissue Specificity ^@ Component of a THAP1/THAP3-HCFC1-OGT complex that contains at least, either THAP1 or THAP3, HCFC1 and OGT. Interacts directly with OGT and HCFC1 (via its HBM) (By similarity).|||Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1.|||Highest levels in heart, liver and kidney. Lower levels in brain and lung. http://togogenome.org/gene/10090:Gnaq ^@ http://purl.uniprot.org/uniprot/P21279|||http://purl.uniprot.org/uniprot/Q3UHH5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(q) subfamily.|||Cell membrane|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Binds NHERF1. Forms a complex with PECAM1 and BDKRB2. Interacts with PECAM1 (By similarity). Interacts with GAS2L2 (PubMed:23994616).|||Golgi apparatus|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems (PubMed:9687499). Required for platelet activation (PubMed:9296496). Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity (PubMed:20624888). Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (PubMed:17938235). Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs) (By similarity). Together with GNA11, required for heart development (PubMed:9687499).|||Histaminylated at Gln-209 residues by TGM2.|||Mice are viable but suffer from cerebellar ataxia and display deficiencies in primary hemostasis due to a defect in platelet activation (PubMed:9296496, PubMed:9391157). Mice lacking Gnaq and Gna11 are embryonic lethal due to cardiomyocyte hypoplasia (PubMed:9687499). Mice lacking Gnaq and with one single intact copy of Gna11, as well as mice lacking Gna11 and with one single intact copy of Gnaq die shortly after birth; lethality is caused by heart malformations (PubMed:9687499). Newborns display craniofacial defects (PubMed:9687499).|||Nucleus|||Nucleus membrane|||Palmitoylated by ZDHHC3 and ZDHHC7 (PubMed:19001095). Palmitoylation occurs in the Golgi and participates in the localization of GNAQ to the plasma membrane (PubMed:19001095). http://togogenome.org/gene/10090:Abl2 ^@ http://purl.uniprot.org/uniprot/B2RQ57|||http://purl.uniprot.org/uniprot/F8VQH0 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. http://togogenome.org/gene/10090:Ninl ^@ http://purl.uniprot.org/uniprot/Q6ZQ12 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with gamma-tubulin and TUBGCP4. Interacts with anaphase promoting complex/cyclosome (APC/C). Interacts with CDC20 and FZR1. Interacts with LCA5 and USH2A (By similarity).|||Involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly (By similarity). Involved in vesicle transport in photoreceptor cells (By similarity).|||Phosphorylated by PLK1 which disrupts its centrosome association and interaction with gamma-tubulin.|||The KEN and D (destructive) boxes are required for the cell cycle-controlled NINL degradation by the APC/C pathway.|||Ubiquitinated by the APC/C complex leading to its degradation.|||centrosome http://togogenome.org/gene/10090:Ywhae ^@ http://purl.uniprot.org/uniprot/P62259|||http://purl.uniprot.org/uniprot/Q5SS40 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm.|||Belongs to the 14-3-3 family.|||Cytoplasm|||Homodimer (By similarity). Heterodimerizes with YWHAZ (By similarity). Interacts with PKA-phosphorylated AANAT (By similarity). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with ARHGEF28 (PubMed:11533041). Interacts with BEX3 (PubMed:11278287). Weakly interacts with CDKN1B (By similarity). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with DENND1A (By similarity). Interacts with GAB2 (By similarity). Interacts with phosphorylated GRB10 (PubMed:15722337). Interacts with KSR1 (PubMed:10409742). Interacts with NDEL1 (PubMed:12796778). Interacts with PI4KB, TBC1D22A and TBC1D22B (By similarity). Interacts with the phosphorylated (by AKT1) form of SRPK2 (By similarity). Interacts with TIAM2 (PubMed:17320046). Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By similarity). Interacts with ZFP36 (via phosphorylated form) (PubMed:21078877). Interacts with SLITRK1 (By similarity). Interacts with HSF1 (via phosphorylated form); this interaction promotes HSF1 sequestration in the cytoplasm in a ERK-dependent manner (By similarity). Interacts with RIPOR2 (By similarity). Interacts with KLHL22; required for the nuclear localization of KLHL22 upon amino acid starvation (By similarity). Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (probably when phosphorylated at 'Ser-171') (PubMed:30611118). Interacts with CRTC3 (probably when phosphorylated at 'Ser-162' and/or 'Ser-273') (PubMed:30611118). Interacts with ATP2B1 and ATP2B3; this interaction inhibits calcium-transporting ATPase activity (By similarity). Interacts with MEFV (By similarity).|||In the 8.5 dpc embryo, expressed throughout the embryo. Within a day, expression was more marked in mesenchyme than elsewhere (e.g. epithelial tissue, where it was generally low), although levels in neural tissue rose again by about 12.5 dpc. This difference was maintained until 15.5 dpc when expression levels started to drop in most tissues, with those of the nervous system, tooth, and kidney being exceptions. Strongly expressed in early mesenchyme. The expression decreased as the mesenchyme differentiated.|||Knockouts show reduced viability with reduced growth and a shortened skull (PubMed:30973865). Mutants show increased thresholds across all frequencies associated with variable amounts of accumulated fluid and exudate containing inflammatory cells in the middle ear, suggesting predisposition to otitis media. The middle ear mucosa appear thickened with granulation tissue in sections and the luminal surface show an open Eustachian tube but abundant clusters of goblet cells with fewer ciliated epithelial cells (PubMed:30973865).|||Melanosome|||Nucleus http://togogenome.org/gene/10090:Skint5 ^@ http://purl.uniprot.org/uniprot/A7XUY5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin and, to a lower extent, testis.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Scgb2b19 ^@ http://purl.uniprot.org/uniprot/J3QM75 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Npm3 ^@ http://purl.uniprot.org/uniprot/Q9CPP0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleoplasmin family.|||Interacts with NPM (via N-terminus). Forms a pentamer with NPM at a ratio 4:1 (NPM3/NPM). Two pentamers form a decamer.|||Nucleus|||Phosphorylated.|||Plays a role in the regulation of diverse cellular processes such as ribosome biogenesis, chromatin remodeling or protein chaperoning. Modulates the histone chaperone function and the RNA-binding activity of nucleolar phosphoprotein B23/NPM. Efficiently mediates chromatin remodeling when included in a pentamer containing NPM3 and NPM.|||Predominantly expressed in testis.|||nucleolus http://togogenome.org/gene/10090:CYTB ^@ http://purl.uniprot.org/uniprot/P00158|||http://purl.uniprot.org/uniprot/Q7JCZ3 ^@ Caution|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome b family.|||Binds 2 heme b groups non-covalently.|||Binds 2 heme groups non-covalently.|||Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis.|||Heme 1 (or BL or b562) is low-potential and absorbs at about 562 nm, and heme 2 (or BH or b566) is high-potential and absorbs at about 566 nm.|||Membrane|||Mitochondrion inner membrane|||The cytochrome bc1 complex contains 11 subunits: 3 respiratory subunits (MT-CYB, CYC1 and UQCRFS1), 2 core proteins (UQCRC1 and UQCRC2) and 6 low-molecular weight proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and a cleavage product of UQCRFS1). This cytochrome bc1 complex then forms a dimer.|||The full-length protein contains only eight transmembrane helices, not nine as predicted by bioinformatics tools. http://togogenome.org/gene/10090:Arsg ^@ http://purl.uniprot.org/uniprot/Q3TYD4 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Displays arylsulfatase activity at acidic pH towards the artificial substrate p-nitrocatechol sulfate (PubMed:25135642). Catalyzes the hydrolysis of the 3-sulfate groups of the N-sulfo-D-glucosamine 3-O-sulfate units of heparin (PubMed:22689975).|||Highly expressed in the spleen, kidney, liver, brain, and testis (at protein level).|||Lysosome|||Mice accumulate heparan sulfate in visceral organs and the central nervous system and develop neuronal cell death and behavioral deficits (PubMed:22689975). This accumulated heparan sulfate exhibits unique non-reducing end structures with terminal N-sulfoglucosamine-3-O-sulfate residues (PubMed:22689975).|||N-glycosylated with both high mannose and complex type sugars.|||The 63-kDa precursor undergoes proteolytic processing in two steps, yielding two fragments in the first step (apparent molecular masses of 44 and 18 kDa). In the second step, the 44-kDa fragment is processed further to the 34- and 10-kDa chains. The 10-kDa chain is a cleavage product of the 44-kDa fragment but linked to the 18-kDa chain through a disulfide bridge.|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Sh2d1a ^@ http://purl.uniprot.org/uniprot/O88890|||http://purl.uniprot.org/uniprot/Q544F1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2.|||Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2. Initially it has been proposed that association with SLAMF1 prevents SLAMF1 binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2. However, by simultaneous interactions, recruits FYN which subsequently phosphorylates and activates SLAMF1 (By similarity). Positively regulates CD244/2B4- and CD84-mediated natural killer (NK) cell functions (PubMed:22683124). Can also promote CD48-, SLAMF6 -, LY9-, and SLAMF7-mediated NK cell activation (PubMed:19648922). In the context of NK cell-mediated cytotoxicity enhances conjugate formation with target cells (PubMed:22683124). May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3.|||Interacts with CD84, CD244, LY9, SLAMF1 and FYN (By similarity). Interacts with NTRK1, NTRK2 and NTRK3.|||T-cells. http://togogenome.org/gene/10090:Hopx ^@ http://purl.uniprot.org/uniprot/Q8R1H0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy (PubMed:12297045, PubMed:12297046). Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated protein refolding (By similarity).|||By the transcription factor NKX2-5 that acts as a direct regulator.|||Cytoplasm|||Expressed in the embryonic and adult heart and in the adult brain, liver, lung, skeletal muscle, intestine and spleen. Throughout embryonic and postnatal development, it is expressed in the myocardium.|||First detected at 7.75 dpc in trophoblasts within extraembryonic membranes, in the lateral wings of the cardiac crescent and in the anterior head folds. At 8.0 dpc, it is expressed along the length of the linear heart tube and in the head folds. Expressed throughout the myocardium at 9.5 dpc and in the branchial arches. At 12.5 dpc, it is expressed in the heart and in the ventricular zone of the neural tube. At 13.5 dpc, it is weakly expressed in the intestinal epithelium. At 13.5 dpc and 15.5 dpc, it is also expressed in skeletal muscle, stratified epithelium (upper aerodigestive tract and skin), epithelium of developing airways, vibrissae, midbrain/hindbrain junction, meninges, mesenchymal cellular condensations that preceded cartilage formation and chondrocytes.|||Interacts with serum response factor (SRF) (PubMed:12297045, PubMed:12297046). Component of a large complex containing histone deacetylases such as HDAC2 (PubMed:12975471). Interacts with the acetylated forms of HSPA1A and HSPA1B. Interacts with HSPA8 (By similarity).|||Mice display partial embryonic lethality and heart failure.|||Nucleus http://togogenome.org/gene/10090:Slc46a1 ^@ http://purl.uniprot.org/uniprot/Q6PEM8 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator superfamily. SLC46A family.|||Cell membrane|||Cytoplasm|||Deletion mutant mice develop severe macrocytic normochromic anemia and ineffective erythropoiesis (PubMed:21346251). More than 90% of mice die by 10 to 12 weeks of age (PubMed:21346251).|||Endosome membrane|||Highly expressed in duodenum, especially in duodenal mucosa, the main site of intestinal heme absorption (PubMed:16143108). Expressed in the retina and retinal pigment epithelium (PubMed:17962486, PubMed:22058337). Weakly expressed in the kidney (PubMed:16143108). Not expressed in duodenum before weaning or in placenta (PubMed:16143108). Weakly or not expressed in brain, heart, lung, skeletal muscle, testis and neonatal liver (PubMed:16143108).|||Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17962486). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17962486). Functions at acidic pH via alternate outward- and inward-open conformation states (By similarity). Protonation of residues in the outward open state primes the protein for transport (By similarity). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (By similarity). Also able to transport antifolate drugs, such as methotrexate and pemetrexed (PubMed:17962486). Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (By similarity). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:16143108). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:22058337). Hence, participates in the trafficking of heme and increases intracellular iron content (By similarity).|||Up-regulated in response to hypoxia, it is however unclear whether such up-regulation is direct or not (PubMed:16143108). Not induced in the duodenum of iron-deficient mice (PubMed:16143108). http://togogenome.org/gene/10090:Josd1 ^@ http://purl.uniprot.org/uniprot/Q9DBJ6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Deubiquitinates monoubiquitinated probes (in vitro). When ubiquitinated, cleaves 'Lys-63'-linked and 'Lys-48'-linked poly-ubiquitin chains (in vitro), hence may act as a deubiquitinating enzyme. May increase macropinocytosis and suppress clathrin- and caveolae-mediated endocytosis. May enhance membrane dynamics and cell motility independently of its catalytic activity (By similarity).|||Interacts with beta-actin/ACTB.|||Monoubiquitinated. Ubiquitination activates deubiquitination activity in vitro.|||Widely expressed (at protein level). http://togogenome.org/gene/10090:Cst11 ^@ http://purl.uniprot.org/uniprot/Q9D269 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||Expressed in epididymis, where it localizes to the proximal caput and also part of the midcaput. Not detected in other tissues tested.|||Has antibacterial activity against the Gram-negative bacteria E.coli. May play a role in sperm maturation and fertilization.|||Secreted|||Up-regulated by testicular factors. However, does not seem to be directly regulated by androgens or estrogen. http://togogenome.org/gene/10090:Ccdc167 ^@ http://purl.uniprot.org/uniprot/Q9D162 ^@ Miscellaneous|||Subcellular Location Annotation ^@ May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane http://togogenome.org/gene/10090:Actbl2 ^@ http://purl.uniprot.org/uniprot/Q8BFZ3 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.|||Belongs to the actin family.|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Monomethylation at Lys-85 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration (By similarity).|||Oxidation of Met-45 and Met-48 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization.|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others (By similarity). Interacts with PFN1 and PFDN1 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Csnk1g3 ^@ http://purl.uniprot.org/uniprot/A0A494BAP2|||http://purl.uniprot.org/uniprot/Q8C4X2 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.|||Cytoplasm|||Expressed in both the striatum and the neocortex.|||Monomer.|||Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling (By similarity). Regulates fast synaptic transmission mediated by glutamate.|||Triazolodiamine 1 is a commercial name for 5-amino-3-([4-(aminosulfonyl)phenyl]amino)-N-(2,6-difluorophenyl)-1H-1,2,4-triazole-1-carbothioamide. http://togogenome.org/gene/10090:Rcl1 ^@ http://purl.uniprot.org/uniprot/Q9JJT0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNA 3'-terminal cyclase family. Type 2 subfamily.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity). Does not have cyclase activity (By similarity).|||nucleolus http://togogenome.org/gene/10090:Pde6g ^@ http://purl.uniprot.org/uniprot/P09174|||http://purl.uniprot.org/uniprot/Q542R6 ^@ Disease Annotation|||Function|||Similarity|||Subunit ^@ Belongs to the rod/cone cGMP-PDE gamma subunit family.|||Deficiency in GMP-PDE activity cause accumulation of cGMP in visual cells. The elevated cGMP levels are associated with degeneration of the photoreceptors and blindness.|||Oligomer composed of two catalytic chains (alpha and beta), an inhibitory chain (gamma) and the delta chain.|||Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones. http://togogenome.org/gene/10090:Il23a ^@ http://purl.uniprot.org/uniprot/Q9EQ14 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of pro-inflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.|||Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity (PubMed:11114383, PubMed:11390512, PubMed:16670770). Released by antigen-presenting cells such as dendritic cells or macrophages, binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R to activate JAK2 and TYK2 which then phosphorylate the receptor to form a docking site leading to the phosphorylation of STAT3 and STAT4 (By similarity). This process leads to activation of several pathways including p38 MAPK or NF-kappa-B and promotes the production of pro-inflammatory cytokines such as interleukin-17A/IL17A (PubMed:19900478). In turn, participates in the early and effective intracellular bacterial clearance (PubMed:16157683). Promotes the expansion and survival of T-helper 17 cells, a CD4-positive helper T-cell subset that produces IL-17, as well as other IL-17-producing cells (PubMed:16648837).|||Belongs to the IL-6 superfamily.|||Heterodimer with IL12B; disulfide-linked (PubMed:11114383). The heterodimer is known as interleukin IL-23 (PubMed:11114383). Interacts with IL23R; this interaction enables recruitment of IL12RB1 (By similarity).|||Mice have no overt phenotype but display compromised humoral and delayed-type hypersensitivity responses. They also have impaired secretion of IL17 and IL17F, higher susceptibility to Klebsiella pneumoniae and Citrobacter rodentium infection, do not develop experimentally-induced autoimmune encephalitis a mouse model of multiple sclerosis, collagen-induced arthritis a rodent model of rheumatoid arthritis and also spontaneous colitis induced by IL10 deficiency a rodent model of inflammatory bowel disease. Transgenic mice expressing Il23a ubiquitously display multiorgan inflammation and infertility, express acute phase genes, have impaired growth and dye prematurely.|||Secreted|||Secreted by activated dendritic cells (at protein level). Detected in various tissues with higher expression in polarized Th1 cells and activated macrophages.|||Up-regulated in trigeminal glanglia after herpes simplex virus type 1 infection, in the lung of mice infected with mycobacteria or Klebsiella pneumoniae. Up-regulated in microglia by combined LPS and IFNG stimulation. Up-regulated by FASLG. http://togogenome.org/gene/10090:Lpl ^@ http://purl.uniprot.org/uniprot/P11152 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Cell membrane|||Detected in white and brown adipose tissue and heart muscle, especially at the lumenal surface of capillaries (PubMed:25066055, PubMed:27811232, PubMed:20620994). Detected on capillary endothelium in the lactating mammary gland (PubMed:27811232). Detected in blood plasma (at protein level) (PubMed:17403372, PubMed:25066055). Expressed in liver, epididymal fat, heart, psoas muscle, lactating mammary gland, adrenal, lung, and ovary. Highest levels in heart and adrenal gland.|||Homodimer (PubMed:25066055). Interacts with GPIHBP1 with 1:1 stoichiometry (PubMed:17403372, PubMed:20620994, PubMed:24726386). Interacts with APOC2; the interaction activates LPL activity in the presence of lipids (By similarity). Interaction with heparan sulfate proteoglycans is required to protect LPL against loss of activity. Associates with lipoprotein particles in blood plasma (By similarity). Interacts with LMF1 and SEL1L; interaction with SEL1L is required to prevent aggregation of newly synthesized LPL in the endoplasmic reticulum (ER), and for normal export of LPL from the ER to the extracellular space (PubMed:25066055). Interacts with SORL1; SORL1 acts as a sorting receptor, promoting LPL localization to endosomes and later to lysosomes, leading to degradation of newly synthesized LPL (By similarity).|||Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage (PubMed:8675619). Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity (By similarity). Mediates margination of triglyceride-rich lipoprotein particles in capillaries (PubMed:24726386). Recruited to its site of action on vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (PubMed:20620994, PubMed:24726386, PubMed:27811232).|||Maximum expression in adipose tissue during early development. In heart, low levels 6 days before birth increasing 278-fold as animals reach adulthood.|||Mice are born at the expected Mendelian rate. At birth, mutant pups have threefold higher plasma triglyceride levels and sevenfold higher VLDL cholesterol levels relative to wild-type. After suckling they become progressively pale, then cyanotic, and die at about 18 hours after birth. At 18 hours after birth, their plasma triglyceride levels reach 15'090 mg/dl, compared to 188 mg/dl for wild-type. At the same time point, VLDL cholesterol levels reach 280 mg/dl in mutant pups, compared to 6 mg/dl in wild-type. Mutant pups show severly reduced adipose tissue, and their livers are deficient in intracellular lipid droplets. Likewise, the numbers of intracellular lipid droplets in skeletal muscle are severely reduced. Lungs display lipid-filled alveoli and dilated capillaries that are engorged with lipoprotein particles. These particles are marginated and seem to block the access of red blood cells to the vascular endothelium.|||N-glycosylated.|||Secreted|||The apolipoprotein APOC2 acts as a coactivator of LPL activity (By similarity). Ca(2+) binding promotes protein stability and formation of the active homodimer. Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (By similarity).|||Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.|||extracellular matrix http://togogenome.org/gene/10090:Maea ^@ http://purl.uniprot.org/uniprot/Q4VC33 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated as component of the CTLH E3 ubiquitin-protein ligase complex (in vitro).|||Cell membrane|||Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. MAEA is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (By similarity). Plays a role in erythroblast enucleation during erythrocyte maturation and in the development of mature macrophages (PubMed:16707498). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (By similarity). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis (PubMed:16707498, PubMed:17071116). Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (PubMed:16707498). May contribute to nuclear architecture and cells division events (By similarity).|||Cytoplasm|||Detected in embryonic fibroblasts (PubMed:16707498). Detected in macrophages (PubMed:17071116). Detected in heart. liver, spleen and kidney (at protein level) (PubMed:16510120).|||Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles (By similarity). Interacts with F-actin (PubMed:16707498).|||Mice die perinatally and exhibit profound alterations in the hematopoietic system. Blood of 14.5-16.5 dpc embryos contained mostly nucleated erythrocytes suggesting a defect in terminal maturation and enucleation of precursor cells. In the fetal liver, large immature erythroblasts predominate, macrophage exhibit an immature morphology and their number is reduced; No erythroblasts are attached to the macrophages suggesting impairment of erythroblastic island formation.|||Nucleus matrix|||The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved. Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity. In addition, the conserved Cys-314 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination.|||cytoskeleton|||nucleoplasm http://togogenome.org/gene/10090:Stx7 ^@ http://purl.uniprot.org/uniprot/Q8BH40 ^@ Similarity ^@ Belongs to the syntaxin family. http://togogenome.org/gene/10090:Znrd2 ^@ http://purl.uniprot.org/uniprot/P56873 ^@ Developmental Stage|||Function|||Miscellaneous|||Tissue Specificity ^@ Expressed in forebrain at 16 dpc.|||Expressed in the early postnatal brain.|||Might play a role in mitosis. Could be a centromere-associated protein. Antigenic molecule. May induce anti-centromere antibodies.|||Two ORFs are contained in the Sssca1 gene, but only this protein is efficiently translated and expressed. http://togogenome.org/gene/10090:Sptlc2 ^@ http://purl.uniprot.org/uniprot/P97363|||http://purl.uniprot.org/uniprot/Q542D6 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adipocyte-specific knockout mice have reduced adipose tissue mass and develop hepatosteatosis with insulin resistance and hyperglycemia.|||Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.|||Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides. Forms dimers of heterodimers with SPTLC1.|||Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (By similarity). Crucial for adipogenesis (PubMed:28698261).|||Endoplasmic reticulum membrane|||Expressed in a variety of tissues. Expressed in brains cortices (at protein level) (PubMed:21994399). Expressed in brown and white adipose tissues (PubMed:28698261, PubMed:27818258). Expressed in liver (PubMed:27818258).|||Expression levels increase upon high-fat diet (at protein level).|||In brains, expressed at low levels after birth, expression highly increases at 2 weeks after birth to decrease and be maintained at 4 weeks after birth until, at least, 18 months (PubMed:21994399). Expression increases in differentiated adipocytes (PubMed:28698261).|||SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides. This mechanism allows to maintain ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis. http://togogenome.org/gene/10090:Csdc2 ^@ http://purl.uniprot.org/uniprot/Q91YQ3 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Nucleus|||RNA-binding factor which binds specifically to the very 3'-UTR ends of both histone H1 and H3.3 mRNAs, encompassing the polyadenylation signal. Might play a central role in the negative regulation of histone variant synthesis in the developing brain (By similarity). http://togogenome.org/gene/10090:Eif3l ^@ http://purl.uniprot.org/uniprot/Q8QZY1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit L family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with RRN3.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm http://togogenome.org/gene/10090:Grip1 ^@ http://purl.uniprot.org/uniprot/Q925T6 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic vesicle|||Detected in early development between postnatal days 3 (P3) and P8 and decreased from P14 in forebrain and cerebellum.|||Endomembrane system|||Endoplasmic reticulum membrane|||Expressed in brain. Isoform 2 is the major isoform in brain. Expressed in oligodendrocyte lineage cells.|||Interacts with EFNB3, GRIA2, GRIA3, GRIPAP1/GRASP1, PPFIA1, PPFIA4, FRAS1, PTPRF, liprins-alpha and the C-terminal tail of PRLHR. Can form homomultimers or heteromultimers with GRIP2 (By similarity). Interacts with EFNB1, EPHA7, EPHB2, KIF5A, KIF5B and KIF5C. Forms a ternary complex with GRIA2 and CSPG4. Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIA2 and leads to AMPAR complex disassembly. Interacts with SLC30A9 and PLCD4. Interacts with BUD23 (By similarity). Forms a complex with NSG1, GRIA2 and STX12; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. Interacts with NSG1 (By similarity).|||Major isoform.|||May be due to exons 2, 10 and 11 skipping.|||May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (By similarity). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity).|||Membrane|||PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1 and EPHB2 and with the C-terminus of PPFIA1 and PPFIA4. PDZ 4 and PDZ 5 mediate interaction with the C-terminus of GRIA2 and GRIA3. PDZ 4, PDZ 5 and PDZ 6 mediate homomultimers. PDZ 7 mediates interaction with PDZ domain of GRASP1. PDZ 6 mediates interaction with the C-terminal of liprins-alpha. PDZ 1, PDZ 2 and PDZ 3 mediate interaction with the PDZ-binding motif of FRAS1. PDZ 4 and PDZ 5 mediate interaction with PRLHR (By similarity). PDZ 7 domain binds CSPG4.|||Palmitoylation of isoform 2.|||Perikaryon|||Postsynaptic cell membrane|||Postsynaptic density|||dendrite http://togogenome.org/gene/10090:Rbbp9 ^@ http://purl.uniprot.org/uniprot/O88851 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the RBBP9 family.|||Expressed in spleen.|||Following chronic low dose of ionizing radiation, expression is up-regulated in male spleen and down-regulated in female spleen (at protein level).|||Interacts with RB1; the interaction disrupts RB1 binding to E2F1. Interacts with RBL1 and RBL2.|||Serine hydrolase whose substrates have not been identified yet. May negatively regulate basal or autocrine TGF-beta signaling by suppressing SMAD2-SMAD3 phosphorylation. May play a role in the transformation process due to its capacity to confer resistance to the growth-inhibitory effects of TGF-beta through interaction with RB1 and the subsequent displacement of E2F1. http://togogenome.org/gene/10090:Fam98a ^@ http://purl.uniprot.org/uniprot/Q3TJZ6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the FAM98 family.|||Interacts (via N- and C-terminus) with DDX1 (By similarity). Interacts (via N- and C-terminus) with C14orf166 (By similarity). Interacts with FAM98B (By similarity). Interacts with PLEKHM1 (via N- and C-terminus) (PubMed:27777970).|||Positively stimulates PRMT1-induced protein arginine methylation (By similarity). Involved in skeletal homeostasis (PubMed:27777970). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (PubMed:27777970). http://togogenome.org/gene/10090:Dlst ^@ http://purl.uniprot.org/uniprot/Q9D2G2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2-oxoacid dehydrogenase family.|||Binds 1 lipoyl cofactor covalently.|||Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex (By similarity). The 2-oxoglutarate dehydrogenase complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion. A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (By similarity).|||Mitochondrion matrix|||Nucleus|||The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A. http://togogenome.org/gene/10090:Cdk17 ^@ http://purl.uniprot.org/uniprot/Q8K0D0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Found in a complex containing CABLES1, CDK16 and TDRD7. Interacts with TDRD7.|||May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). http://togogenome.org/gene/10090:Gnrhr ^@ http://purl.uniprot.org/uniprot/D3Z6P7|||http://purl.uniprot.org/uniprot/Q01776|||http://purl.uniprot.org/uniprot/Q6P8H4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the developing pituitary gland at 18.5 dpc.|||Membrane|||Pituitary gland.|||Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Rcor2 ^@ http://purl.uniprot.org/uniprot/Q8C796 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CoREST family.|||During early development (7 dpc to 8.5 dpc), it is uniformly distributed, with a higher expression in the presumptive neural tissue (head region) while it is not expressed in the heart. From 9 dpc on, it becomes increasingly restricted to the developing brain and spinal cord. With the exception of the floor plate, it is expressed in many cell clusters in the neural tube at that stage. Expressed in dorsal root ganglia and in the neural retina (sensory layer of the retina) of embryos from 11 dpc on throughout development. During mid-gestation, it is particularly expressed in neural tissue thereby shifting to the intermediate and distal layers of the expanding intraneural domains. From late gestational stages on, pronounced expression is detectable only in selected areas of the brain such as the retrospinal cortex. Expressed in neural cell layers in the hypothalamic region at postnatal day 5. In adult brains, it is expressed in many neural cells of the differentiated cortex. Expression is also observed in non-neural tissue such as the developing limbs where it becomes restricted to the interdigital areas. Strongly expressed in the odontoblast layer of the developing teeth and the maxillary bone. In the cerebellum, it is already expressed before the lobules form. At 14 dpc, it is uniformly distributed in the cerebellar rudiment. When lobulation becomes evident, expression is detectable only in the proliferating granule cells of the outermost layer (external granular layer).|||May act as a component of a corepressor complex that represses transcription.|||Nucleus|||Predominantly, but not exclusively, expressed in neural tissue. Strongly expressed in neural domains of the developing brain of the developing mouse CNS. http://togogenome.org/gene/10090:Fbf1 ^@ http://purl.uniprot.org/uniprot/A2A870 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Broadly expressed.|||Cell junction|||Interacts with PARD3 (By similarity). May interact with FAS cytoplasmic domain (By similarity). Interacts with TRAPPC14 (By similarity).|||Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis (By similarity).|||centriole|||spindle pole http://togogenome.org/gene/10090:Cnksr3 ^@ http://purl.uniprot.org/uniprot/Q8BMA3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the CNKSR family.|||Cytoplasm|||Expressed in kidney.|||Interacts with epithelial sodium channel ENaC. Interacts directly with SCNN1A (ENaC subunit alpha) and SCNN1B (ENaC subunit beta) C-terminal tails. Interacts with ENaC regulatory proteins NEDD4L, RAF1 and SGK1.|||Involved in transepithelial sodium transport. Regulates aldosterone-induced and epithelial sodium channel (ENaC)-mediated sodium transport through regulation of ENaC cell surface expression. Acts as a scaffold protein coordinating the assembly of an ENaC-regulatory complex (ERC).|||The PDZ domain is required for interaction with ENaC and SGK1, but not for interaction with NEDDL4 and RAF1. http://togogenome.org/gene/10090:Morf4l1 ^@ http://purl.uniprot.org/uniprot/P60762|||http://purl.uniprot.org/uniprot/Q569V4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC. MORF4L1 may also participate in the formation of NuA4 related complexes which lack the KAT5/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. Component of the mSin3A histone deacetylase complex, which includes SIN3A, HDAC2, ARID4B, MORF4L1, RBBP4/RbAp48, and RBBP7/RbAp46. Interacts with RB1 and KAT8. May also interact with PHF12 and one or more as yet undefined members of the TLE (transducin-like enhancer of split) family of transcriptional repressors. Interacts with the N-terminus of MRFAP1 (By similarity). Found in a complex composed of MORF4L1, MRFAP1 and RB1. Interacts with the entire BRCA complex, which contains BRCA1, PALB2, BRCA2 and RAD51. Interacts with PALB2 (By similarity). Forms a complex with MSL1 and NUPR1 (By similarity).|||Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also a component of the mSin3A complex which acts to repress transcription by deacetylation of nucleosomal histones. Required for homologous recombination repair (HRR) and resistance to mitomycin C (MMC). Involved in the localization of PALB2, BRCA2 and RAD51, but not BRCA1, to DNA-damage foci (By similarity).|||Nucleus http://togogenome.org/gene/10090:Eif4g2 ^@ http://purl.uniprot.org/uniprot/A0JNY7|||http://purl.uniprot.org/uniprot/Q62448 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases.|||Belongs to the eukaryotic initiation factor 4G family.|||Interacts with the serine/threonine protein kinases MKNK1 and MKNK2. Binds EIF4A and EIF3. Interacts with MIF4GD (By similarity). Interacts with DAZAP2 (By similarity).|||Phosphorylation; hyperphosphorylated during mitosis.|||This gene has been shown to be extensively edited in the liver of APOBEC1 transgenic animals. Its aberrant editing could contribute to the potent oncogenesis induced by overexpression of APOBEC1. The aberrant edited sequence, called NAT1, is likely to be a fundamental translational repressor.|||Ubiquitously expressed in all tissues examined. http://togogenome.org/gene/10090:Dysf ^@ http://purl.uniprot.org/uniprot/A0A0N4SUN3|||http://purl.uniprot.org/uniprot/A0A0N4SV63|||http://purl.uniprot.org/uniprot/A0A0N4SVX9|||http://purl.uniprot.org/uniprot/A0A0N4SWH3|||http://purl.uniprot.org/uniprot/E9Q423|||http://purl.uniprot.org/uniprot/Q9ESD7 ^@ Disease Annotation|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All seven C2 domains associate with lipid membranes in a calcium-dependent manner. Domains C2 1 and 3 have the highest affinity for calcium, the C2 domain 1 seems to be largely unstructured in the absence of bound ligands (By similarity).|||Belongs to the ferlin family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Defects in Dysf are the cause of a slowly progressive muscular dystrophy observed in SJL mice. It affects primarily the proximal muscles and it is inherited as autosomal recessive trait.|||Expressed in skeletal and cardiac muscles (at protein level). Expressed in skeletal muscle and heart. Also found in brain, liver and kidney.|||Interacts with CAV3. Interacts with AHNAK; the interaction is direct and Ca(2+)-independent. Interacts with AHNAK2; the interaction is direct and Ca(2+)-independent (By similarity). Interacts with ANXA1; the interaction is Ca(2+)- and injury state-dependent. Interacts with ANXA2; the interaction is Ca(2+)- and injury state-dependent. Interacts with CACNA1S and PARVB. Interacts with TRIM72/MG53; interaction is required for transport to sites of cell injury during repair patch formation. Interacts with RIPOR2; this interaction occurs during early myogenic differentiation (By similarity).|||Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress.|||Membrane|||Mice lacking Dysf maintain a functional dystrophin glycoprotein complex (DGC) but their muscle cells are defective in repairing the plasma membrane disruptions and accumulates vesicles at the sarcolemma. They develop a progressive muscular dystrophy and cardiomyopathy.|||The sequence differs significantly from amino acid position 1855.|||sarcolemma http://togogenome.org/gene/10090:Tmem106a ^@ http://purl.uniprot.org/uniprot/Q8VC04 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activates macrophages and polarizes them into M1-like macrophages through the activation of the MAPK and NF-kappaB signaling pathway (PubMed:26215746). Upon activation, up-regulates the expression of CD80, CD86, CD69 and MHC II on macrophages, and induces the release of pro-inflammatory cytokines such as TNF, IL1B, IL6, CCL2 and nitric oxide (PubMed:26215746). May play a role in inhibition of proliferation and migration (By similarity).|||Belongs to the TMEM106 family.|||Cell membrane|||Cell surface expression is increased by Thioglycollate in elicited macrophages.|||Expressed in liver, spleen, lung, kidney, lymph nodes and adipose tissue (at protein level) (PubMed:26215746). Expressed by macrophages (PubMed:26215746). http://togogenome.org/gene/10090:Sostdc1 ^@ http://purl.uniprot.org/uniprot/Q9CQN4 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sclerostin family.|||Expression was first detected at 11 dpc throughout the surface of the embryo, and it was most intense in the head region on the surfaces of the mandibular, maxillary, and frontonasal processes. At 11.5 dpc expression is detected in the first and second branchial arches, pharynx and metanephros. At 12 dpc-14 dpc, expression was intense and strikingly confined to developing ectodermal organs. The vibrissae, tylotrich hair follicles, tongue papillae, and tooth germs as well as the ear auricle. Also expressed intensely in kidney epithelium in the stalk and tips of ureter as well as in the spermatic ducts in the testis. At 17.5 dpc strong expression was restricted to kidney tubules and ameloblasts in teeth, and moderate expression was observed in hair follicles, choroids plexus of the fourth cerebral ventricle of the brain. First detected on 12.5 dpc in interstitial cell of the testis and increased towards 14.5 dpc. On 8 dpp (day post partum) highly expression was detected in kidney and weakly in skin.|||Highly expressed in kidney at renal collecting ducts level and weakly in brain.|||Interacts with BMP2, BMP4, BMP6 and BMP7 with high affinity.|||May be involved in the onset of endometrial receptivity for implantation/sensitization for the decidual cell reaction. Enhances Wnt signaling and inhibits TGF-beta signaling (By similarity). Directly antagonizes activity of BMP2, BMP4, BMP6 and BMP7 in a dose-dependent manner.|||Secreted|||Up-regulated by BMP2 and BMP7. Down-regulated by FGF4 and SHH. http://togogenome.org/gene/10090:Pkp4 ^@ http://purl.uniprot.org/uniprot/Q3UIX3|||http://purl.uniprot.org/uniprot/Q68FH0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the beta-catenin family.|||Cell membrane|||Interacts (via the C-terminus) with FRMPD2 (via the PDZ 2 domain). Interacts with PDZD2. Interacts with RHOA; the interaction is detected at the midbody. Interacts with ECT2; the interaction is detected at the midbody (By similarity). Interacts with CCDC85B (By similarity).|||Midbody|||Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques (By similarity).|||desmosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Vmn1r2 ^@ http://purl.uniprot.org/uniprot/A2AMT6 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Or11j4 ^@ http://purl.uniprot.org/uniprot/Q8VFT6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Oxtr ^@ http://purl.uniprot.org/uniprot/P97926 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.|||Cell membrane|||Receptor for oxytocin. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Bicd2 ^@ http://purl.uniprot.org/uniprot/D3Z390|||http://purl.uniprot.org/uniprot/Q921C5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates and stabilizes the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (PubMed:11483508, PubMed:25035494, PubMed:24986880, PubMed:22956769). Facilitates the binding of RAB6A to the Golgi by stabilizing its GTP-bound form (PubMed:25962623). Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport via its interaction with RAB6A and recruitment of the dynein-dynactin motor complex (PubMed:12447383, PubMed:25962623). Contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1. During G2 phase of the cell cycle, associates with RANBP2 at the nuclear pores and recruits dynein and dynactin to the nuclear envelope to ensure proper positioning of the nucleus relative to centrosomes prior to the onset of mitosis (PubMed:20386726).|||Belongs to the BicD family.|||Cytoplasm|||Golgi apparatus|||Nucleus envelope|||Part of a tripartite complex with dynein and dynactin, acts an adapter linking the dynein motor complex and dynactin (By similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with NEK9 (By similarity). Interacts with DCTN2 (PubMed:11483508, PubMed:22956769). Interacts with RAB6A (PubMed:12447383, PubMed:25962623). Interacts with DNAI1 (By similarity). Interacts with DYNLL1, DYNC1H1, DYNC1I2 and DCTN1 (PubMed:22956769). Forms a complex with dynein and dynactin (PubMed:24986880). The dynein-dynactin-BICD2 ternary complex (DDB) binds preferentially to tyrosinated microtubules than to detyrosinated microtubules (PubMed:26968983). Interacts with RANBP2, RAB6A and KIF5A (PubMed:20386726). Interacts with KIF1C (By similarity).|||Phosphorylated by NEK9 in vitro.|||The fourth coiled coil region is involved in Golgi targeting and in the interaction with DCTN2.|||Ubiquitously expressed with high expression in the spinal cord.|||cytoskeleton|||nuclear pore complex http://togogenome.org/gene/10090:Or2ad1 ^@ http://purl.uniprot.org/uniprot/Q8VFG3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pdx1 ^@ http://purl.uniprot.org/uniprot/P52946 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates insulin and somatostatin gene transcription. Key regulator of islet peptide hormone expression but also responsible for the development of the pancreas, most probably by determining maturation and differentiation of common pancreatic precursor cells in the developing gut. As part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Binds the DNA sequence 5'-CC[CT]TAATGGG-3'.|||At 8.5 dpc, detected in the gut epithelium from which the pancreatic buds are formed. Transient expression in pancreatic ducts, endocrine and acinar cells. Down-regulated around 10.5 dpc when expression becomes restricted to differentiated beta-cells.|||Belongs to the Antp homeobox family. IPF1/XlHbox-8 subfamily.|||Duodenum and pancreas (Langerhans islet beta cells and small subsets of endocrine non-beta-cells, at low levels in acinar cells).|||Expression is repressed by FOXO1 in pancreatic beta-cells.|||Interacts with the basic helix-loop-helix domains of TCF3(E47) and NEUROD1 and with HMG-I(Y). Interacts with the methyltransferase SETD7 (By similarity). Interacts with SPOP. Part of a PDX1:PBX1b:MEIS2b complex.|||Nucleus|||Phosphorylated by the SAPK2 pathway at high intracellular glucose concentration. Phosphorylated by HIPK2 on Ser-269 upon glucose accumulation. This phosphorylation mediates subnuclear localization shifting. Phosphorylation by PASK may lead to translocation into the cytosol.|||The Antp-type hexapeptide mediates heterodimerization with PBX on a regulatory element of the somatostatin promoter.|||The homeodomain, which contains the nuclear localization signal, not only mediates DNA-binding, but also acts as a protein-protein interaction domain for TCF3(E47), NEUROD1 and HMG-I(Y).|||cytosol http://togogenome.org/gene/10090:Cyp24a1 ^@ http://purl.uniprot.org/uniprot/Q3TWW0|||http://purl.uniprot.org/uniprot/Q64441 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24-oxidation pathway, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid. Hydroxylates at C-24 or C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin.|||Belongs to the cytochrome P450 family.|||By 1,25-dihydroxyvitamin D(3) in kidney.|||Mitochondrion http://togogenome.org/gene/10090:Fam222a ^@ http://purl.uniprot.org/uniprot/Q6PGH4 ^@ Similarity ^@ Belongs to the FAM222 family. http://togogenome.org/gene/10090:Leo1 ^@ http://purl.uniprot.org/uniprot/Q5XJE5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LEO1 family.|||Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. Involved in polyadenylation of mRNA precursors. Connects PAF1C to Wnt signaling (By similarity).|||Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. The PAF1 complex interacts with PHF5A (PubMed:27749823). Interacts with TCEA1, SUPT5H and CTNNB1 (By similarity). Interacts with SETD5 (PubMed:27864380).|||Nucleus http://togogenome.org/gene/10090:Sypl ^@ http://purl.uniprot.org/uniprot/O09117|||http://purl.uniprot.org/uniprot/Q3TVX7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the synaptophysin/synaptobrevin family.|||Cytoplasmic vesicle membrane|||Melanosome|||Membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Actn2 ^@ http://purl.uniprot.org/uniprot/Q5FW75|||http://purl.uniprot.org/uniprot/Q9JI91 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha-actinin family.|||F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (By similarity).|||Homodimer; antiparallel. Also forms heterodimers with ACTN3. Interacts with ADAM12, MYOZ1, MYOZ2 and MYOZ3. Interacts via its C-terminal region with the LDB3 PDZ domain. Interacts with XIRP2. Interacts with DST (via N-terminus). Interacts with PARVB. Interacts with SYNPO2 (By similarity).|||Ubiquitinated by FBXL22, leading to proteasomal degradation.|||Z line http://togogenome.org/gene/10090:Cacng2 ^@ http://purl.uniprot.org/uniprot/O88602|||http://purl.uniprot.org/uniprot/Q3ZB20 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Brain.|||Defects in Cacng2 cause the stargazer (stg) phenotype. Stg mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear.|||Membrane|||Phosphorylation of Thr-321 by PKA impairs interaction with DLG1 and DLG4.|||Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).|||Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.|||The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma. Interacts with the PDZ domains of DLG4/PSD-95 and DLG1/SAP97. May interact with GOPC. Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with GRIA1 and GRIA2 (By similarity). Interacts with MPP2.|||synaptosome http://togogenome.org/gene/10090:Or52b3 ^@ http://purl.uniprot.org/uniprot/E9Q542 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrpl54 ^@ http://purl.uniprot.org/uniprot/Q9CPW3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL54 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Or52z14 ^@ http://purl.uniprot.org/uniprot/E9PV95 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpsm1 ^@ http://purl.uniprot.org/uniprot/Q6IR34 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GPSM family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in brain at 14 dpc.|||Expressed in neural progenitor cells (at protein level).|||Golgi apparatus membrane|||Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction.|||Interacts with GNAI1 and GNAI2 preferentially in their GDP-bound state. May also interact with GNAO1. Interacts with INSC/inscuteable and FRMPD1 (By similarity). Interacts with GNAI3. Interacts with STK11/LKB1 and MACF1.|||Phosphorylation regulates interaction with G(i/o) alpha.|||The GoLoco domains are essential for the GDI activity toward G(i/o) alpha. The GoLoco domains mediate interaction with G(i/o) alpha (By similarity).|||cytosol http://togogenome.org/gene/10090:Dnajb11 ^@ http://purl.uniprot.org/uniprot/Q99KV1 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ As a co-chaperone for HSPA5 it is required for proper folding, trafficking or degradation of proteins. Binds directly to both unfolded proteins that are substrates for ERAD and nascent unfolded peptide chains, but dissociates from the HSPA5-unfolded protein complex before folding is completed. May help recruiting HSPA5 and other chaperones to the substrate. Stimulates HSPA5 ATPase activity. It is necessary for maturation and correct trafficking of PKD1.|||Contains high-mannose Endo H-sensitive carbohydrates.|||Cys-169, Cys-171, Cys-193 and Cys-196 form intramolecular disulfide bonds. The preferential partner for each Cys is not known (By similarity).|||Endoplasmic reticulum lumen|||Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Binds to denatured substrates in an ATP-independent manner. Interacts via the J domain with HSPA5 in an ATP-dependent manner (By similarity).|||PubMed:11584023 reported a cytosolic, as well as nuclear subcellular location. This result was obtained using an N-terminally GFP-tagged construct which most probably affected signal peptide-driven targeting to the ER. As a consequence, the in vivo revelance of the observed interaction with APOBEC1, a nuclear protein, is dubious. http://togogenome.org/gene/10090:Add3 ^@ http://purl.uniprot.org/uniprot/Q3UNK1|||http://purl.uniprot.org/uniprot/Q8BM29|||http://purl.uniprot.org/uniprot/Q9QYB5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldolase class II family. Adducin subfamily.|||Cell membrane|||Cleavage fragment 1-357 is expressed in the brain and the expression increases with age (at protein level). The fragment is expressed in the cortex, hippocampal CA1 region and hippocampal dentate gyrus in tau P301S transgenic mice, a mouse model for Alzheimer disease (AD) (at protein level). The fragment is only weakly expressed in non-transgenic mouse brain sections (at protein level).|||Comprised of three regions: a N-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.|||Cytoplasm|||Heterodimer of an alpha and a gamma subunit.|||Membrane|||Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping. Binds to calmodulin (By similarity). Involved in myogenic reactivity of the renal afferent arteriole (Af-art), renal interlobular arteries and middle cerebral artery (MCA) to increased perfusion pressure. Involved in regulation of potassium channels in the vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. Involved in regulation of glomerular capillary pressure, glomerular filtration rate (GFR) and glomerular nephrin expression in response to hypertension. Involved in renal blood flow (RBF) autoregulation. Plays a role in podocyte structure and function. Regulates globular monomer actin (G-actin) and filamentous polymer actin (F-actin) ratios in the primary podocytes affecting actin cytoskeleton organization. Regulates expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex and the primary podocytes. Regulates expression of nephrin in the glomeruli and in the primary podocytes, expression of nephrin and podocinin in the renal cortex, and expression of focal adhesion proteins integrin alpha-3 and integrin beta-1 in the glomeruli. Involved in cell migration and cell adhesion of podocytes, and in podocyte foot process effacement. Regulates expression of profibrotics markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E-cadherin, and mesenchymal markers vimentin and alpha-SMA (By similarity). Promotes the growth of neurites (PubMed:33992672).|||Proteolytically cleaved by asparagine endopeptidase (AEP) into 2 fragments. Overexpression of the 1-357 fragment induces neuronal apoptosis, and overexpression of either 1-357 or 358-706 fragment increases the degeneration of dendritic spines. Overexpression of the 1-357 fragment impairs neurite outgrowth by downregulating the expression of Rac2, and induces synaptic dysfunction and cognitive impairments in tau P301S transgenic mice, a mouse model for Alzheimer disease (AD).|||Sumoylated.|||cytoskeleton http://togogenome.org/gene/10090:Sts ^@ http://purl.uniprot.org/uniprot/P50427 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Catalyzes the conversion of sulfated steroid precursors, such as dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate to the free steroid.|||Endoplasmic reticulum membrane|||Homodimer.|||Microsome membrane|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Gabrb1 ^@ http://purl.uniprot.org/uniprot/P50571|||http://purl.uniprot.org/uniprot/Q53WT3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB1 sub-subfamily.|||Cell membrane|||Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine (By similarity). Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.|||Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains. Binds UBQLN1. Interacts with KCTD8, KCTD12, KCTD12B and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Tanc1 ^@ http://purl.uniprot.org/uniprot/Q0VGY8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TANC family.|||Interacts probably directly with DLG1, DLG4, HOMER1. Interacts with DLGAP1, INA, CAMK2A, GRIN2B and GRIA1. Interacts with TNIK and MINK1 (By similarity).|||May be a scaffold component in the postsynaptic density.|||Phosphorylated; by MINK1 and TNIK upon stimulation by RAP2A.|||Postsynaptic density http://togogenome.org/gene/10090:Lrfn2 ^@ http://purl.uniprot.org/uniprot/Q80TG9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRFN family.|||Expression starts around 11.5-12.5 dpc. At 11.5 dpc, detected in the outer layer of the telencephalic vesicles. This pattern of expression continues until 17.5 dpc with expression in the cortical plate, but not in the inner layer of the cerebral cortex, including subplate, ventricular zone, and subventricular zone. As also detected in the hippocampus, amygdala and widely in diencephalic nuclei.|||Forms heteromeric complexes with LRFN1, LRFN3, LRFN4 and LRFN5. Can form homomeric complexes, but not across cell junctions (By similarity). Interacts with DLG4. Directly interacts with DLG1, DLG2 and DLG3 (By similarity). Directly interacts with 2 NMDA receptor subunits GRIN1 and GRIN2A (By similarity).|||Glycosylated.|||Membrane|||Postsynaptic cell membrane|||Predominantly expressed in the brain, with a weak, but broad expression in the cerebral cortex and diencephalic nuclei. Strongly expressed in both the pyramidal layer and the dentate gyrus of the hippocampus. Also detected in other parts of the central nervous system, including the olfactory bulb, pons, cerebellum, and medulla oblongata, as well as in the peripheral nervous system, such as the ganglia of cranial nerves and the dorsal root ganglion during gestation.|||Promotes neurite outgrowth in hippocampal neurons. Enhances the cell surface expression of 2 NMDA receptor subunits GRIN1 and GRIN2A (By similarity). May play a role in redistributing DLG4 to the cell periphery.|||Synapse|||The PDZ-binding motif is required for cell surface expression, neurite outgrowth promotion and interaction with DLG1, DLG3 and DLG4. http://togogenome.org/gene/10090:Igbp1 ^@ http://purl.uniprot.org/uniprot/Q61249 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of the phosphatases PP2A, PP4 and PP6 by protecting their partially folded catalytic subunits from degradative polyubiquitination until they associate with regulatory subunits.|||Belongs to the IGBP1/TAP42 family.|||Cytoplasm|||Expressed in spleen, thymus, liver and brain. Ubiquitously expressed in B lineage cell lines.|||Interacts with PPP2CB, and with PP4 and PP6. Interacts with MID2. Interacts with ubiquitin (By similarity). Interacts with partially folded PPP2CA, but not with the fully active protein. Interacts with MID1.|||Monoubiquitination by MID1 triggers calpain-mediated cleavage and switches IGBP1 activity from protective to destructive.|||Phosphorylated.|||The UIM domain is required for protective effect on PP2A. http://togogenome.org/gene/10090:Dnajb6 ^@ http://purl.uniprot.org/uniprot/O54946 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70 (PubMed:18373498). Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Also reduces cellular toxicity and caspase-3 activity (By similarity).|||Homooligomer. Interacts with BAG3, HSPB8 and STUB1 (By similarity). Interacts with ALKBH1 (PubMed:18163532). Interacts with HSP70, KRT18 and PTTG (By similarity). Interacts with Slfn1; promoting nuclear translocation of Slfn1 (PubMed:18373498).|||Nucleus|||Z line|||perinuclear region http://togogenome.org/gene/10090:Cnr1 ^@ http://purl.uniprot.org/uniprot/A0A385KNU8|||http://purl.uniprot.org/uniprot/P47746 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in brain neurons (at protein level) (PubMed:22388959). Detected throughout the striatum, cortex and hippocampus, with highest levels in the lateral striatum (PubMed:15606779, PubMed:10891614, PubMed:22388959). In rostral brain regions, high expression levels in the dorsal lateral striatum, while in the caudal brain regions, high levels are observed in the ventral lateral striatum (PubMed:10891614). Expressed in neurons (PubMed:10891614). In the hypothalamus, expressed in both GABAergic and glutamatergic presynaptic terminals of POMC neurons (at protein level) (PubMed:25869131, PubMed:25707796). Expressed in striated muscles, including skeletal muscles (gastrocnemius and rectus abdominis) and myocardium (at protein level) (PubMed:26671069, PubMed:27826249). Expressed in the liver, with highest levels in Kupffer cells and lower levels in endothelial cells as well as hepatocytes, particularly in perivascular areas (at protein level) (PubMed:15864349, PubMed:21987372). The hepatic expression level is up-regulated in obese mice compared to lean animals (PubMed:21987372).|||G-protein coupled receptor for cannabinoids, including endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (PubMed:9888857, PubMed:22388959). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain (PubMed:9888857, PubMed:27828947). Signaling typically involves reduction in cyclic AMP (PubMed:8832654, PubMed:27828947). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses (PubMed:25707796, PubMed:27828947). At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2 (PubMed:27828947). In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression (PubMed:25869131). In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake (PubMed:25707796). In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission (PubMed:22388959). Also reduces excitatory synaptic transmission (PubMed:27828947). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (By similarity). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia (PubMed:22841573). In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (PubMed:15864349). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes (PubMed:15864349, PubMed:21987372). May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake (PubMed:21987372). Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (PubMed:26671069). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712).|||G-protein coupled receptor for cannabinoids, including endocannabinoids (eCBs), such as N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG). Signaling typically involves reduction in cyclic AMP.|||Hemopressin, a peptide derived from hemoglobin subunit alpha (HBA1 and/or HBA2), acts as an antagonist peptide: hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and subsequent signaling.|||High-fat diet also increases the hepatic levels of CNR1 ligand anandamide, but not that of 2-arachidonoylglycerol.|||Interacts (via C-terminus) with CNRIP1 (By similarity). Associates with G protein alpha subunits, including G(i) alpha-1/GNAI1, G(i) alpha-3/GNAI3 and G(o)-alpha/GNAO1; palmitoylation is important for interaction with GNAI3 and GNAO1 (PubMed:27828947).|||Interacts (via C-terminus) with CNRIP1.|||May contribute to the development of diet-induced obesity and several obesity-associated features, such as dyslipidemia and liver steatosis, regulating peripheral lipogenesis, energy expenditure and feeding behavior. In the liver, mediates cannabinoid-induced de novo lipogenesis and reduces fatty acid catabolism (PubMed:15864349, PubMed:21987372). In muscles, affects energy expenditure through mitochondrial metabolism (PubMed:22841573, PubMed:26671069). Induces leptin production by adipocytes and reduces LRP2-mediated leptin clearance in the kidney. The resulting hyperleptinemia causes resistance to the anorexic and weight-reducing effects of leptin (PubMed:22841573). In response to cannabinoids, drives the release of orexigenic beta-endorphin from hypothalamic POMC neurons, hence promoting food intake (PubMed:25707796). The use of peripherally-restricted inverse agonists in diet-induced obese mice reduces appetite, body weight, hepatic steatosis, and insulin resistance (PubMed:22841573).|||Membrane|||Mitochondrion outer membrane|||No visible phenotype, although mutant mice present a mild impairment in the adaptation to new environment. Mutant mice do not respond to cannabinoids, such as anandamide. The acute effects of opiates are not affected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome are strongly reduced (PubMed:9888857). On high-fat diet, mutant mice remain lean, their metabolic and hormonal profile are unchanged, and they do not develop fatty liver, despite having caloric intake similar to that of wild-type mice (PubMed:15864349).|||Palmitoylation at Cys-416 is important for recruitment at both plasma membrane and lipid rafts and association with G protein alpha subunits.|||Presynapse|||Synapse|||Up-regulated by endocannabinoid anandamide/AEA (PubMed:21987372, PubMed:23955712). Down-regulated by IL1B (PubMed:23955712). Up-regulated in the liver of animals on a high-fat diet compared to regular diet (PubMed:15864349, PubMed:21987372).|||axon http://togogenome.org/gene/10090:Mvk ^@ http://purl.uniprot.org/uniprot/Q3UEB4|||http://purl.uniprot.org/uniprot/Q9R008 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GHMP kinase family. Mevalonate kinase subfamily.|||Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis.|||Cytoplasm|||Farnesyl pyrophosphate and geranyl pyrophosphate inhibit mevalonate kinase activity by binding competitively at the ATP-binding sites.|||Homodimer.|||Peroxisome http://togogenome.org/gene/10090:Lypd5 ^@ http://purl.uniprot.org/uniprot/Q9D7Z7 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Spata20 ^@ http://purl.uniprot.org/uniprot/Q80YT5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Detected in 28- and 75-day-old mouse testes. No expression detected at 21 days.|||May play a role in fertility regulation.|||Secreted http://togogenome.org/gene/10090:Krt12 ^@ http://purl.uniprot.org/uniprot/Z4YJD9 ^@ Similarity ^@ Belongs to the intermediate filament family. http://togogenome.org/gene/10090:Calhm6 ^@ http://purl.uniprot.org/uniprot/Q8C9E8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CALHM family.|||Membrane|||Pore-forming subunit of a voltage-gated ion channel. http://togogenome.org/gene/10090:Aqp9 ^@ http://purl.uniprot.org/uniprot/D3YYD6|||http://purl.uniprot.org/uniprot/Q4FK77|||http://purl.uniprot.org/uniprot/Q9JJJ3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Forms a water channel with a broad specificity. Also permeable glycerol and urea. Mediates passage of a wide variety of small, non-charged solutes including carbamides, polyols, purines, and pyrimidines.|||Membrane http://togogenome.org/gene/10090:Mup20 ^@ http://purl.uniprot.org/uniprot/Q5FW60 ^@ Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Constitutes approximately 10% of the total major urinary protein composition in the urine of C57BL/6 males but is barely detectable in the urine of BALB/c males.|||Detected in urine of males but absent from female urine (at protein level).|||Male pheromone which stimulates female sexual attraction to male urinary scent and promotes a strong learned attraction to the airborne urinary odor of an individual male (PubMed:20525243, PubMed:31996852). Promotes spatial learning by rapidly conditioning preference for its remembered location among females and competitor males so that animals prefer to spend time in the site even when scent is absent (PubMed:23239735). In addition to promoting a rapid attraction response, also elicits ultrasonic vocalizations and urinary scent marking in females which do not occur immediately after exposure (PubMed:31996852). Stimulates hippocampal neurogenesis and cell proliferation in the subventricular zone in females (PubMed:25972792). Promotes male aggressive behavior (PubMed:18064011). Response to Mup20 is mediated by a neural circuit extending from the accessory olfactory bulb to a subset of nitric oxidase synthase-expressing neurons in the medial amygdala (PubMed:31996852). As well as acting as a pheromone itself, binds most of the male pheromone, 2-sec-butyl-4,5-dihydrothiazole, in urine and is responsible for its slow release from scent marks (PubMed:15934926, PubMed:25279835).|||Secreted http://togogenome.org/gene/10090:Cfhr2 ^@ http://purl.uniprot.org/uniprot/Q4LDF6 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Nat10 ^@ http://purl.uniprot.org/uniprot/Q8K224 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNA cytidine acetyltransferase family. NAT10 subfamily.|||Embryonic lethality before 14.5 dpc (PubMed:29703891). Heterozygous mice are healthy and show enhanced healthspan in a Hutchinson-Gilford progeria syndrome (HGPS) mouse model; molecular mechanisms explaining the relation between Nat10 activity and nuclear architecture defects in HGPS mouse models are however unclear (PubMed:29703891).|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with THUMPD1. Interacts with SUN1 (via N-terminus). Interacts with TERT.|||RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine (ac4C) modification on mRNAs, 18S rRNA and tRNAs. Catalyzes ac4C modification of a broad range of mRNAs, enhancing mRNA stability and translation. mRNA ac4C modification is frequently present within wobble cytidine sites and promotes translation efficiency. Mediates the formation of ac4C at position 1842 in 18S rRNA (By similarity). May also catalyze the formation of ac4C at position 1337 in 18S rRNA (By similarity). Required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis (By similarity). Catalyzes the formation of ac4C in serine and leucine tRNAs (By similarity). Requires the tRNA-binding adapter protein THUMPD1 for full tRNA acetyltransferase activity but not for 18S rRNA acetylation. In addition to RNA acetyltransferase activity, also able to acetylate lysine residues of proteins, such as histones, microtubules, p53/TP53 and MDM2, in vitro. The relevance of the protein lysine acetyltransferase activity is however unsure in vivo. Activates telomerase activity by stimulating the transcription of TERT, and may also regulate telomerase function by affecting the balance of telomerase subunit assembly, disassembly, and localization. Involved in the regulation of centrosome duplication by acetylating CENATAC during mitosis, promoting SASS6 proteasome degradation (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||nucleolus http://togogenome.org/gene/10090:Plscr5 ^@ http://purl.uniprot.org/uniprot/J3QM92 ^@ Function|||Similarity ^@ Belongs to the phospholipid scramblase family.|||May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. http://togogenome.org/gene/10090:Dlgap3 ^@ http://purl.uniprot.org/uniprot/B1AS06|||http://purl.uniprot.org/uniprot/Q3TY61|||http://purl.uniprot.org/uniprot/Q6PFD5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAPAP family.|||Cell membrane|||Highly expressed in central and peripherical nervous system (at protein level).|||Interacts with DLG4/PSD-95.|||May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/SAP90 at the plasma membrane.|||Postsynaptic density|||Synapse http://togogenome.org/gene/10090:Lnx1 ^@ http://purl.uniprot.org/uniprot/O70263 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65.|||Interacts with CXADR. Interacts with MAGEB18 and MAGEF1 (By similarity). Interacts with the phosphotyrosine interaction domain of all isoforms of NUMB. IGSF5/JAM4 interacts with isoform 2 through the second PDZ domain, other isoforms may also interact with IGSF5/JAM4.|||Isoform 1 and isoform 2 are expressed in the heart. Isoform 1 is also expressed in kidney, lung and skeletal muscle while isoform 2 is also expressed in brain.|||Isoform 2 provides an endocytic scaffold for IGSF5/JAM4.|||The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient.|||The PDZ 1 domain participates in the interaction with the PID domain of NUMB, and participates in the isoform-specific ubiquitination of NUMB. The PDZ 2 domain of isoform 2 participates in the interaction with IGSF5/JAM4, other isoforms containing this domain may also interact with IGSF5/JAM4. http://togogenome.org/gene/10090:Pald1 ^@ http://purl.uniprot.org/uniprot/P70261 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 9.5 and 10.5 dpc, weak but general expression in the intersomitic mesenchyme. Higher levels of expression in the intersomitic vessels and other developing small and large blood vessels. Expressed in the notochord and the roof and floor plates of the neural tube. Expressed along rhombomeres 2 and 4, as well as pharyngeal arches 1 and 2, possibly in neural crest cells. No expression in the somites. At 14.5 dpc, predominantly expressed in all vessels, capillaries (at protein level), arteries and veins. Strong vascular expression observed in neural tissue, skeletal muscle, skin, kidney, liver, and along the gastrointestinal tract. Nonvascular expression detected in heart myocardium, lung and kidney mesenchyme (at protein level). During postnatal vascular development, expression shifts from capillary and venous vessels to arteries, from endothelial cells to vascular smooth muscle cells.|||Belongs to the paladin family.|||Vascular expression detected in the central nervous system, kidney, lung, heart, skeletal muscle, white adipose tissue (WAT), brown adipose tissue, liver, pancreas and spleen. Not expressed in all vessels: for instance, not expressed in capillaries in the brain, and expressed mainly in large vessels in the heart, WAT, liver, pancreas and kidney. Predominant nonvascular expression in myocardium and lung mesenchyme. In large vessels, primarily expressed by smooth muscle cells, but occasionally detected at low levels in the endothelium. Expressed in various cells of the hematopoietic lineage.|||cytosol http://togogenome.org/gene/10090:Ppm1m ^@ http://purl.uniprot.org/uniprot/Q8BU27 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Nucleus|||Widely expressed with highest levels in testis and lower levels in lung, kidney and brain. http://togogenome.org/gene/10090:Or2w4 ^@ http://purl.uniprot.org/uniprot/Q5SZZ8|||http://purl.uniprot.org/uniprot/Q8VG14 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Epha4 ^@ http://purl.uniprot.org/uniprot/Q03137 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Early endosome|||Expressed in inner and outer pillar cells of the organ of Corti (at protein level) (PubMed:30639848). Highest expression in the adult brain and retina and also detectable in kidney, lung, skeletal muscle and thymus. Not detected in heart and liver. Expressed in myogenic progenitor cells (PubMed:27446912).|||Found in both the 10-day embryonic brain and body tissues. In the embryonic brain, expressed in the developing cortex of the telencephalon and major cortical tracts. Also expressed in the hippocampus, fornix and striatal cells and tracts. In the diencephalon, strongly expressed in thalamus, hypothalamus and thalamo-cortical projection. Also expressed in red nuclei of the mesencephalon and in the cerebellum. In the spinal cord, persistent expression occurs in the dorsal funiculus and ventral gray matter. In myogenic progenitor cells, highly expressed at 11.5 dpc and ceases its expression at the late fetal stage (17.5 dpc) (PubMed:27446912).|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation. Forms a ternary complex composed of ADAM10, CADH1 and EPHA4; within the complex, CADH1 is cleaved by ADAM10 which disrupts adherens junctions (PubMed:30639848).|||Mice are viable and fertile but display a loss of coordination of limb movement associated with disruptions of cortico-spinal tract. They also display altered development of the thymic epithelium which leads to a defective T-cells development.|||Postsynaptic density membrane|||Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity (PubMed:17719550). Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections (PubMed:9789074, PubMed:17719550, PubMed:17785183). May also control the segregation of motor and sensory axons during neuromuscular circuit developmen (PubMed:18403711). In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis (PubMed:17143272). In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation (PubMed:15537875, PubMed:16802330). Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium (PubMed:16818734). During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (PubMed:30639848). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (PubMed:31439799).|||The protein kinase domain mediates interaction with NGEF.|||adherens junction|||axon|||dendrite http://togogenome.org/gene/10090:Tm6sf1 ^@ http://purl.uniprot.org/uniprot/D3YX52|||http://purl.uniprot.org/uniprot/P58749 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TM6SF family.|||Broad expression.|||Lysosome membrane|||May function as sterol isomerase.|||Membrane http://togogenome.org/gene/10090:Ssrp1 ^@ http://purl.uniprot.org/uniprot/Q08943 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SSRP1 family.|||Chromosome|||Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA. Also acts as a transcriptional coactivator for p63/TP63.|||Embryos die soon after implantation while preimplantation blastocysts are defective for cell outgrowth.|||Interacts with MYOG (via C-terminal region) (PubMed:23364797). Component of the FACT complex, a stable heterodimer of SSRP1 and SUPT16H. Also a component of a CK2-SPT16-SSRP1 complex which forms following UV irradiation, composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B. Binds to histone H3-H4 tetramers, but not to intact nucleosomes. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Interacts with isoform gamma of TP63. Interacts with FYTTD1/UIF (By similarity). Interacts with SRF (By similarity). Interacts with NEK9 (By similarity).|||Nucleus|||Phosphorylated by CK2 following UV but not gamma irradiation. Phosphorylation inhibits its DNA-binding activity (By similarity).|||Sumoylated.|||Ubiquitinated. Polyubiquitinated following caspase cleavage resulting in degradation of the N-terminal ubiquitinated part of the cleaved protein (By similarity).|||nucleolus http://togogenome.org/gene/10090:Myof ^@ http://purl.uniprot.org/uniprot/A0A286YDF5|||http://purl.uniprot.org/uniprot/Q69ZN7 ^@ Cofactor|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ferlin family.|||Binds Ca(2+). The ions are bound to the C2 1 domain.|||Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress. Involved in endocytic recycling. Implicated in VEGF signal transduction by regulating the levels of the receptor KDR.|||Cell membrane|||Cytoplasmic vesicle membrane|||Expressed in myoblasts (at protein level). Expressed in endothelial cells.|||Interacts with EHD1 (PubMed:21177873). Interacts with EHD2; the interaction is direct (PubMed:21177873). Interacts with DNM2 and KDR (PubMed:21177873). Interacts with RIPOR2 (By similarity).|||Membrane|||Mice lacking Myof display fewer large multinucleated myotubes and are impaired in their ability to regenerate skeletal muscle after injury. They display a defective membrane repair in endothelial cells. They show also a delayed endocytic recycling.|||Nucleus membrane|||The C2 1 domain associates with lipid membranes in a calcium-dependent manner.|||Up-regulated during myotube formation. http://togogenome.org/gene/10090:Or6c38 ^@ http://purl.uniprot.org/uniprot/Q8VGC4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hoxb9 ^@ http://purl.uniprot.org/uniprot/P20615 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Prokr1 ^@ http://purl.uniprot.org/uniprot/Q9JKL1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed at high levels in the heart, skeletal muscle and pancreas. Expressed at lower levels in the brain, lung, liver and kidney.|||Receptor for prokineticin 1. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of p44/p42 mitogen-activated protein kinase. May play a role during early pregnancy (By similarity). http://togogenome.org/gene/10090:Msl3l2 ^@ http://purl.uniprot.org/uniprot/G3X992 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Cfap20 ^@ http://purl.uniprot.org/uniprot/Q8BTU1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CFAP20 family.|||Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Involved in the regulation of the size and morphology of cilia. Required for axonemal microtubules polyglutamylation.|||Expressed at high levels in germinal vesicle stage oocytes at the mRNA level. Expression progressively decreases until blastocyst stage (PubMed:15803458). Detected in later embryonic stages from 9.5 to 19.5 dpc. At 11.5 dpc, the expression is widespread, with no preference for any particular organ or structure (PubMed:8688464).|||Nucleus|||Widely expressed, with highest levels in testis and lowest in muscle.|||centriole|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Ube2d3 ^@ http://purl.uniprot.org/uniprot/P61079|||http://purl.uniprot.org/uniprot/Q4QQL2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction. Together with RNF135, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production. Together with ZNF598, catalyzes ubiquitination of 40S ribosomal proteins in response to ribosome collisions. In cooperation with the GATOR2 complex, catalyzes 'Lys-6'-linked ubiquitination of NPRL2.|||Belongs to the ubiquitin-conjugating enzyme family.|||Cell membrane|||Endosome membrane|||Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex; when Cullin is neddylated, the interaction between the E2 and the SCF complex is strengthened. Interacts with DAPK3. Interacts with BRCA1; the DNA damage checkpoint promotes the association with BRCA1 after ionizing radiation. Interacts non-covalently with ubiquitin. Interacts with E3 ubiquitin-protein ligase CBLC. Interacts with UBTD1 (By similarity). Interacts with RIGI and RNF135; involved in RIGI ubiquitination and activation (By similarity).|||Phosphorylated by AURKB. http://togogenome.org/gene/10090:Picalm ^@ http://purl.uniprot.org/uniprot/Q3TD51|||http://purl.uniprot.org/uniprot/Q570Z8|||http://purl.uniprot.org/uniprot/Q7M6Y3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PICALM/SNAP91 family.|||Binds to clathrin; involves primarily the C-terminal sequences, but the full-length protein is required for full binding capacity. Binds phosphatidylinositol 4,5- bisphosphate. Interacts with PIMREG; this interaction may change the subcellular location into the nucleus. Interacts with AP2A1 (via its alpha-appendage domain). Interacts (via N-terminus) with VAMP2; VAMP3; VAMP7 and VAMP8 (Via N-terminus). Interacts with LC3/MAP1LC3A.|||Cell membrane|||Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8. In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors. Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF).|||Golgi apparatus|||Membrane|||Nucleus|||PICALM-deficient mice suffer from severe anemia due to ineffective erythropoiesis in the bone marrow. In addition, they exhibit impaired clathrin-mediated internalization of transferrin leading to iron metabolism abnormalities.|||Skins and livers of 1-week-old mice.|||clathrin-coated pit|||clathrin-coated vesicle http://togogenome.org/gene/10090:Naa50 ^@ http://purl.uniprot.org/uniprot/Q6PGB6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family. GNAT subfamily.|||Component of the N-terminal acetyltransferase E (NatE) complex at least composed of NAA10, NAA15 and NAA50 (By similarity). Interacts with NAA10 (By similarity). Interacts with NAA15 (By similarity). Predominantly interacts with NAA15 in the N-terminal acetyltransferase A complex (NatA complex); the interactions reduce the acetylation activity of the NatA complex (By similarity). Component of the N-terminal acetyltransferase E (NatE)/HYPK complex at least composed of NAA10, NAA15, NAA50 and HYPK (By similarity). Within the complex interacts with NAA15 (By similarity). Its capacity to interact with the NatA complex is reduced by HYPK (By similarity). Interacts with NAA35 (PubMed:16484612).|||Cytoplasm|||N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine (By similarity). Has a broad substrate specificity: able to acetylate the initiator methionine of most peptides, except for those with a proline in second position (By similarity). Also displays N-epsilon-acetyltransferase activity by mediating acetylation of the side chain of specific lysines on proteins (By similarity). Autoacetylates in vivo (By similarity). The relevance of N-epsilon-acetyltransferase activity is however unclear: able to acetylate H4 in vitro, but this result has not been confirmed in vivo (By similarity). Component of N-alpha-acetyltransferase complexes containing NAA10 and NAA15, which has N-alpha-acetyltransferase activity (By similarity). Does not influence the acetyltransferase activity of NAA10 (By similarity). However, it negatively regulates the N-alpha-acetyltransferase activity of the N-terminal acetyltransferase A complex (also called the NatA complex) (By similarity). The multiprotein complexes probably constitute the major contributor for N-terminal acetylation at the ribosome exit tunnel, with NAA10 acetylating all amino termini that are devoid of methionine and NAA50 acetylating other peptides (By similarity). Required for sister chromatid cohesion during mitosis by promoting binding of CDCA5/sororin to cohesin: may act by counteracting the function of NAA10 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Myo5b ^@ http://purl.uniprot.org/uniprot/G5E8G6 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Vmn1r251 ^@ http://purl.uniprot.org/uniprot/K9J7G2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ndst3 ^@ http://purl.uniprot.org/uniprot/D3YXE5|||http://purl.uniprot.org/uniprot/E9PZJ4|||http://purl.uniprot.org/uniprot/Q9EQH7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. NDST subfamily.|||Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Has high deacetylase activity but low sulfotransferase activity.|||Golgi apparatus membrane|||Membrane|||Monomer.|||Strongly expressed strongly in brain. Expressed at high level at embryonic day 11 compared to other stages of development. Weakly expressed in adult heart, kidney, muscle, endothelial cells and testis but not in other tissues.|||The presence of 4 different heparan sulfate N-deacetylase/N-sulfotransferase enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/sulfation reactions, whereas other later on fill in or extend already modified heparan sulfate sequences. http://togogenome.org/gene/10090:Ppfia1 ^@ http://purl.uniprot.org/uniprot/B2RXQ2|||http://purl.uniprot.org/uniprot/B2RXW8 ^@ Similarity ^@ Belongs to the liprin family. Liprin-alpha subfamily. http://togogenome.org/gene/10090:Or52s1b ^@ http://purl.uniprot.org/uniprot/Q7TRR7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Moxd2 ^@ http://purl.uniprot.org/uniprot/Q7TT41 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the copper type II ascorbate-dependent monooxygenase family.|||Binds 2 copper ions per subunit.|||Expressed at low levels in thymus and testis.|||Membrane http://togogenome.org/gene/10090:Or8g23 ^@ http://purl.uniprot.org/uniprot/Q9EQB4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trappc13 ^@ http://purl.uniprot.org/uniprot/Q3TIR1 ^@ Similarity|||Subunit ^@ Belongs to the TRAPPC13 family.|||Part of the multisubunit TRAPP (transport protein particle) complex. http://togogenome.org/gene/10090:Or4f6 ^@ http://purl.uniprot.org/uniprot/Q8VF85 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il27ra ^@ http://purl.uniprot.org/uniprot/O70394 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Down-regulated on differentiation of CD4+ T-cells in both Th1 and TH2 cells.|||Expressed in CD4+ and CD8+ T-cells, B-cells, natural killer cells and macrophages. Highest levels in CD4+ T-cells and natural killer cells. Expression highest in Th0 cells.|||Membrane|||Receptor for IL27. Requires IL6ST/GP130 to mediate signal transduction in response to IL27. This signaling system acts through STAT3 and STAT1. Involved in the regulation of Th1-type immune responses. Also appears to be involved in innate defense mechanisms.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Kif1a ^@ http://purl.uniprot.org/uniprot/E9Q9G6|||http://purl.uniprot.org/uniprot/E9QAN4|||http://purl.uniprot.org/uniprot/G3UW47|||http://purl.uniprot.org/uniprot/Q3UH16|||http://purl.uniprot.org/uniprot/Q6P5H4|||http://purl.uniprot.org/uniprot/Q6TA13 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||axon http://togogenome.org/gene/10090:Or5ac17 ^@ http://purl.uniprot.org/uniprot/F6ZUS0|||http://purl.uniprot.org/uniprot/Q7TS39 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pde4d ^@ http://purl.uniprot.org/uniprot/A2RSH1|||http://purl.uniprot.org/uniprot/Q01063 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium and/or manganese ions.|||Cytoplasm|||Expressed in brain (at protein level). Isoform 7 is detected in heart, brain, lung, kidney and testis.|||Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Binds ARRB2. Interacts with PDE4DIP (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.|||Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.|||Inhibited by rolipram. Activated by phosphatidic acid (By similarity).|||Membrane|||Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.|||Up-regulated by cAMP and follicle-stimulating hormone.|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Dido1 ^@ http://purl.uniprot.org/uniprot/Q8C9B9 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts specifically (via PHD-type zinc finger) with histone H3 that is trimethylated at 'Lys-4' (H3K4me3), histone phosphorylation at 'Thr-3' or 'Thr-6' disrupts this binding and promotes translocation of DIDO1 from chromatin to the mitotic spindle during mitosis.|||Nucleus|||Required for early embryonic stem cell development (By similarity). Putative transcription factor, weakly pro-apoptotic when overexpressed.|||The PHD-type zinc finger forms an aromatic cage around H3K4me3.|||Ubiquitous. Expressed at intermediate levels.|||Up-regulated during apoptosis.|||spindle http://togogenome.org/gene/10090:Awat2 ^@ http://purl.uniprot.org/uniprot/A2ADU0|||http://purl.uniprot.org/uniprot/Q6E1M8 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 11-cis retinoids act as allosteric modulators of acyl-CoA retinol O-fatty-acyltransferase (ARAT) activity by suppressing esterification of 9-cis, 13-cis, or all-trans retinols concurrently increasing the enzyme specificity toward 11-cis isomer.|||Acyltransferase that catalyzes the formation of ester bonds between fatty alcohols and fatty acyl-CoAs to form wax monoesters (PubMed:15220349). Shows a preference for medium chain acyl-CoAs from C12 to C16 in length and fatty alcohols shorter than C20, as the acyl donor and acceptor, respectively (PubMed:15220349). Also possesses acyl-CoA retinol acyltransferase (ARAT) activity that catalyzes 11-cis-specific retinyl ester synthesis (PubMed:28096191). Shows higher catalytic efficiency toward 11-cis-retinol versus 9-cis-retinol, 13- cis-retinol and all-trans-retinol substrates (By similarity).|||Belongs to the diacylglycerol acyltransferase family.|||Endoplasmic reticulum membrane|||Expressed in Mueller cells of the retina (at protein level) (PubMed:24799687). Abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid (PubMed:15220349).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Monomer. http://togogenome.org/gene/10090:Parvb ^@ http://purl.uniprot.org/uniprot/Q3UGT9|||http://purl.uniprot.org/uniprot/Q9ES46 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration (By similarity).|||Belongs to the parvin family.|||Cell membrane|||Expressed predominantly in heart and moderately in spleen, lung and skeletal muscle.|||Interacts with ILK, ARHGEF6, PXN (via LD motifs), ACTN2 and actin (By similarity). Interacts with DYSF.|||Membrane|||Phosphorylated by ILK.|||Z line|||cytoskeleton|||focal adhesion|||lamellipodium|||sarcomere http://togogenome.org/gene/10090:Arfgef1 ^@ http://purl.uniprot.org/uniprot/G3X9K3 ^@ Activity Regulation|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Golgi apparatus|||Homodimer. Interacts with ARFGEF2/BIG2; both proteins are probably part of the same or very similar macromolecular complexes. Interacts with FKBP2. Interacts with MYO9B. Interacts with PRKAR1A and PRKAR2A. Interacts with PPP1CC. Interacts with NCL, FBL, NUP62 and U3 small nucleolar RNA. Interacts with DPY30. Interacts with PDE3A. Interacts with KANK1. Interacts with TBC1D22A and TBC1D22B.|||Inhibited by brefeldin A.|||Membrane|||Nucleus|||Nucleus matrix|||Phosphorylated. In vitro phosphorylated by PKA reducing its GEF activity and dephosphorylated by phosphatase PP1 (By similarity).|||Promotes guanine-nucleotide exchange on ARF1 and ARF3. Promotes the activation of ARF1/ARF3 through replacement of GDP with GTP. Involved in vesicular trafficking. Required for the maintenance of Golgi structure; the function may be independent of its GEF activity. Required for the maturaion of integrin beta-1 in the Golgi. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. Inhibits GAP activity of MYO9B probably through competitive RhoA binding. The function in the nucleus remains to be determined (By similarity).|||nucleolus|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Efna2 ^@ http://purl.uniprot.org/uniprot/P52801|||http://purl.uniprot.org/uniprot/Q3USB4 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ephrin family.|||Binds to the receptor tyrosine kinases EPHA3, EPHA4 and EPHA5. Interacts with EPHA8; activates EPHA8.|||Cell membrane|||Cell surface GPI-bound ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. With the EPHA2 receptor may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.|||Expressed in myogenic progenitor cells.|||In myogenic progenitor cells, highly expressed, at least as early as 11.5 dpc, expression decreases gradually until adulthood.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Or5d38 ^@ http://purl.uniprot.org/uniprot/Q7TR27 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stard7 ^@ http://purl.uniprot.org/uniprot/Q8R1R3 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in epithelial cells of airways, peripheral bronchioles and alveoli, as well as in the basal cell layer of the epidermis (at protein level).|||May play a protective role in mucosal tissues by preventing exaggerated allergic responses.|||Mitochondrion|||Proteolytically cleaved by PARL.|||The viability of homozygous knockout embryos is dramatically decreased after 10.0 dpc. Surviving animals have a normal life expectancy, but males are infertile. Ovalbumin sensitization and challenge of heterozygous mice results in a significant increase in pulmonary inflammation, mucous cell metaplasia, airway hyperresponsiveness and ovalbumin-specific IgE compared with wild-type animals. This exacerbation is associated with an increase in CD4(+) IL13(+) T helper cells, as well as an increase IL4, IL5 and IL13 cytokine production in lungs. Sensitized and/or challenged mutant animals show an increased lung epithelial permeability and activation of pro-inflammatory dendritic cells. At 6-7 months of age, about 30% of heterozygous mice develop skin lesions, with significant thickening of the epidermis, including the cornified layer, predominately on the ears and back. Lesions are accompanied by vigorous scratching. In the lesions, IL4, IL5 and IL13 cytokine production is increased and serum IgE levels are up-regulated at the time of appearance of skin lesions. http://togogenome.org/gene/10090:Apobr ^@ http://purl.uniprot.org/uniprot/Q8VBT6 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Finds at the highest levels in 7 dpc, then progressively lower at 11 dpc and 15 dpc, and finally very diminished at the 17 dpc.|||Highly expressed in spleen, lung and skeletal muscle, and weakly in brain, heart, kidney, and testis.|||Homodimer.|||Increased in high-fat diet ATM (adipose tissue macrophages).|||Macrophage receptor that binds to the apolipoprotein B48 (APOB) of dietary triglyceride (TG)-rich lipoproteins (TRL) or to a like domain of APOB in hypertriglyceridemic very low density lipoprotein (HTG-VLDL). Binds and internalizes TRL when out of the context of the macrophage. May provide essential lipids to reticuloendothelial cells. Could also be involved in foam cell formation with elevated TRL and remnant lipoprotein (RLP). Mediates the rapid high-affinity uptake of chylomicrons (CM), HTG-VLDL, and trypsinized (tryp) VLDL devoid of APOE in vitro in macrophages.|||There are 2 forms in macrophages, the membrane-binding proteins 200 kDa (MBP 200) and 235 kDa (MBP 235), that can be reduced into a single active ligand-binding species with intermediate mobility (MBP 200R). http://togogenome.org/gene/10090:Dbx1 ^@ http://purl.uniprot.org/uniprot/P52950 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the H2.0 homeobox family.|||Could have a role in patterning the central nervous system during embryogenesis. Has a key role in regulating the distinct phenotypic features that distinguish two major classes of ventral interneurons, V0 and V1 neurons. Regulates the transcription factor profile, neurotransmitter phenotype, intraspinal migratory path and axonal trajectory of V0 neurons, features that differentiate them from an adjacent set of V1 neurons.|||During early and mid-gestation, dbx expression is restricted to the telencephalon, diencephalon, dorsal mesencephalon and spinal cord. At later gestational stages, dbx expression continues in the dorsal mesencephalon and diencephalon, in which expression is more restricted than at the earlier stages.|||Nucleus http://togogenome.org/gene/10090:Yeats4 ^@ http://purl.uniprot.org/uniprot/Q9CR11 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromatin reader component of the NuA4 histone acetyltransferase (HAT) complex, a complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (By similarity). Specifically recognizes and binds acylated histone H3, with a preference for histone H3 diacetylated at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac) or histone H3 diacetylated at 'Lys-14' and 'Lys-27' (H3K14ac and H3K27ac) (By similarity). Also able to recognize and bind crotonylated histone H3 (By similarity). May also recognize and bind histone H3 succinylated at 'Lys-122' (H3K122succ); additional evidences are however required to confirm this result in vivo (By similarity). Plays a key role in histone variant H2AZ1/H2A.Z deposition into specific chromatin regions: recognizes and binds H3K14ac and H3K27ac on the promoters of actively transcribed genes and recruits NuA4-related complex to deposit H2AZ1/H2A.Z (By similarity). H2AZ1/H2A.Z deposition is required for maintenance of embryonic stem cell (PubMed:29900004).|||Component of numerous complexes with chromatin remodeling and histone acetyltransferase activity. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Interacts with MLLT10/AF10. Also interacts with the SWI/SNF component SMARCB1/BAF47, TACC1 and TACC2, and the nuclear matrix protein NUMA1.|||Nucleus|||The YEATS domain specifically recognizes and binds acylated histones, with a preference for histone H3 diacetylated at 'Lys-14' and 'Lys-27' (H3K14ac and H3K27ac). http://togogenome.org/gene/10090:H2aj ^@ http://purl.uniprot.org/uniprot/Q8R1M2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (By similarity).|||Monoubiquitination of Lys-120 (H2AXK119ub) gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties (By similarity).|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription (By similarity).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Sh3bgrl ^@ http://purl.uniprot.org/uniprot/Q9JJU8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to function as an adapter protein that bridges proteins together or proteins with mRNAs. May function as a ubiquitin ligase-substrate adapter. Additionally, associates with translating cytoplasmic ribosomes and may promote the expression of specific mRNAs.|||Belongs to the SH3BGR family.|||Cell membrane|||Monomer. Interacts with PFN1/Profilin-1. Interacts with ERBB2. Interacts with ATG12. Interacts with BECN1. Interacts with translating ribosomes.|||The SH3-binding domain is buried in the tertiary structure, and it therefore unclear whether it directly mediates protein-binding.|||cytosol http://togogenome.org/gene/10090:Or52w1 ^@ http://purl.uniprot.org/uniprot/Q8VF03 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxl12 ^@ http://purl.uniprot.org/uniprot/Q9EPX5 ^@ Function|||Subunit ^@ Interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Mediates the polyubiquitination and proteasomal degradation of CAMK1 leading to disruption of cyclin D1/CDK4 complex assembly which results in G1 cell cycle arrest in lung epithelia (By similarity). http://togogenome.org/gene/10090:Usp4 ^@ http://purl.uniprot.org/uniprot/A0A0A6YW28|||http://purl.uniprot.org/uniprot/P35123 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Belongs to the peptidase C19 family. USP4 subfamily.|||Cytoplasm|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (By similarity). Deubiquitinates PDPK1 (By similarity). Deubiquitinates TRIM21 (By similarity). Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (By similarity). Deubiquitinates HAS2 (By similarity). Deubiquitinates RHEB in response to EGF signaling, promoting mTORC1 signaling (By similarity). May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (By similarity). This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (By similarity). May also play a role in the regulation of quality control in the ER (By similarity).|||Expressed in brain, kidney, liver and spleen (at protein level).|||Interacts with RB1 (both dephosphorylated and hypophosphorylated forms) (PubMed:11571651). Interacts with RBL1 and RBL2 (PubMed:11571651). Interacts with ADORA2A (via cytoplasmic C-terminus); the interaction is direct. Interacts with SART3; recruits USP4 to its substrate PRPF3 (By similarity).|||Monoubiquitinated by TRIM21. Ubiquitination does not lead to its proteasomal degradation. Autodeubiquitinated.|||Nucleus|||Overexpression leads to oncogenic transformation of NIH 3T3 cells.|||Phosphorylated at Ser-445 by PKB/AKT1 in response to EGF stimulus, promoting its ability deubiquitinate RHEB.|||The DUSP and ubiquitin-like 1 domains promote ubiquitin release and thus enhance USB4 catalytic activity. However, these domains do not bind ubiquitin.|||The completion of the deubiquitinase reaction is mediated by the DUSP and ubiquitin-like 1 domains which promotes the release of ubiquitin from the catalytic site enabling subsequent reactions to occur. http://togogenome.org/gene/10090:Ctse ^@ http://purl.uniprot.org/uniprot/P70269 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase A1 family.|||Endosome|||Expressed abundantly in the stomach, club cells and alveolar macrophages of the lung, brain microglia, spleen and activated B-lymphocytes. Not expressed in resting B-lymphocytes.|||Glycosylated. The nature of the carbohydrate chain varies between cell types. In fibroblasts, the proenzyme contains a high mannose-type oligosaccharide, while the mature enzyme contains a complex-type oligosaccharide.|||Homodimer; disulfide-linked.|||May have a role in immune function. Probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation. May play a role in activation-induced lymphocyte depletion in the thymus, and in neuronal degeneration and glial cell activation in the brain. http://togogenome.org/gene/10090:Cracd ^@ http://purl.uniprot.org/uniprot/Q5PR69 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Directly interacts with actin-capping proteins CAPZA1, CAPZA2 and CAPZB; this interaction decreases the binding of capping proteins to actin.|||Expressed in the small intestine (at protein level).|||Involved in epithelial cell integrity by acting on the dynamics of the actin cytoskeleton (PubMed:30361697). Positively regulates the actin polymerization, by inhibiting the interaction of actin-capping proteins with actin (By similarity).|||Knockout mice display adenoma development in the small intestine in an age-dependent manner. They also develop pulmonary lesions resembling early small cell lung cancer and solid-pseudopapillary neoplasm of the pancreas. Tumors from mutant animals show increased expression of Wnt/beta-catenin target genes without the alteration of other signaling pathways. Intestinal tumors exhibit disorganized and decreased levels of F-actin.|||cytosol http://togogenome.org/gene/10090:Dyrk4 ^@ http://purl.uniprot.org/uniprot/Q8BI55 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylation on Tyr-379 in the activation loop is required for kinase activity.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.|||Cytoplasm|||Highly expressed in testes.|||Possible non-essential role in spermiogenesis. http://togogenome.org/gene/10090:Rap1b ^@ http://purl.uniprot.org/uniprot/Q99JI6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by guanine nucleotide-exchange factor (GEF) EPAC2 in a cAMP-dependent manner.|||Belongs to the small GTPase superfamily. Ras family.|||Cell junction|||Cell membrane|||GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction. Plays a role in the establishment of basal endothelial barrier function (By similarity).|||Heterodimer with RAP1GAP (By similarity). Interacts with EPAC2 (By similarity). Interacts with SGSM1 (By similarity). Interacts with SGSM2 (By similarity). Interacts with SGSM3 (By similarity). Interacts with KRIT1 (By similarity). Interacts with RAP1GDS1 (By similarity).|||cytosol http://togogenome.org/gene/10090:Unc93a ^@ http://purl.uniprot.org/uniprot/Q710D3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the unc-93 family.|||Cell membrane http://togogenome.org/gene/10090:Nxf2 ^@ http://purl.uniprot.org/uniprot/Q4ZGD8|||http://purl.uniprot.org/uniprot/Q8R499|||http://purl.uniprot.org/uniprot/Q99MW6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NXF family.|||Cytoplasm|||nucleoplasm http://togogenome.org/gene/10090:Fancl ^@ http://purl.uniprot.org/uniprot/Q9CR14 ^@ Caution|||Disease Annotation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM (By similarity). In complex with FANCF, FANCA and FANCG, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins. Interacts with FANCI (By similarity). Interacts with GGN. Interacts (via the RING-type zinc finger) with UBE2T and UBE2W.|||Cytoplasm|||Defects in Fancl are a cause of the gcd (germ cell deficient) mutant phenotype, which leads to reduced numbers of precursor germ cells and adult sterility, probably due to a reduced precursor germ cells proliferation.|||Despite its name, it does not contain a PHD-type zinc finger, but contains a RING-type zinc finger. Moreover, PHD-type zinc fingers do not have any ubiquitin ligase activity.|||Nucleus|||The RING-type zinc finger domain is monoubiquitinated in the presence of UBE2T and UBE2W.|||The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2.|||Ubiquitin ligase protein that mediates monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCI. May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth. http://togogenome.org/gene/10090:Emc10 ^@ http://purl.uniprot.org/uniprot/Q3TAS6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EMC10 family.|||Component of the ER membrane protein complex (EMC).|||Endoplasmic reticulum membrane|||Knockout mice show no cardiovascular phenotype at baseline. After myocardial infarction however, capillarization of the infarct border zone is impaired and the animals develop larger infarct scars and more pronounced left ventricular remodeling and systolic dysfunction compared with wild-type mice.|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (By similarity). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways (PubMed:28931551).|||Secreted|||Up-regulated in the left ventricle 3 days after myocardial infarction (MI). Expressed predominantly by monocytes and macrophages from bone marrow, spleen, and peripheral blood 3 days after MI (protein level). http://togogenome.org/gene/10090:Stard5 ^@ http://purl.uniprot.org/uniprot/Q9EPQ7 ^@ Function|||Tissue Specificity ^@ Expressed in most tissues, with highest levels in liver and in kidney.|||May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols. http://togogenome.org/gene/10090:Golph3l ^@ http://purl.uniprot.org/uniprot/H3BJ07|||http://purl.uniprot.org/uniprot/Q8R088 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GOLPH3/VPS74 family.|||Expressed in a subset of tissues tested with higher expression in salivary gland, small intestine and skin (at protein level).|||Golgi stack membrane|||Homooligomer. Does not interact MYO18; differs from GOLPH3 by its inability to interact with MYO18. May interact with ARF1 (By similarity).|||Membrane|||Phosphatidylinositol-4-phosphate-binding protein that may antagonize the action of GOLPH3 which is required for the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Dsg3 ^@ http://purl.uniprot.org/uniprot/O35902|||http://purl.uniprot.org/uniprot/Q3UFC6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.|||Expressed in embryo at 7 to 17 dpc.|||Expressed in epidermis.|||Interacts with PKP2.|||Membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Vwa1 ^@ http://purl.uniprot.org/uniprot/Q8R2Z5 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed at high levels in the chondrocytes. Detected in the vasculature of neural tissues, in basement membrane structures of the peripheral nervous system, in the apical ectodermal ridge of developing limb buds, and in skeletal and cardiac muscle (at protein level).|||Homodimer or homomultimer; disulfide-linked. Interacts with HSPG2.|||N-glycosylated.|||Promotes matrix assembly (PubMed:18757743). Involved in the organization of skeletal muscles and in the formation of neuromuscular junctions (By similarity).|||Restricted to the presumptive articular cartilage zone prior to joint cavitation and to the articular cartilage and fibrocartilaginous elements in the joint, spine and sternum during embryonic development. Detected from 9.5 dpc in the vasculature of the central nervous system. At 16.5 dpc, present in intervertebral disks of the spinal cord, lip epithelium and developing oral and tooth germ epithelia (at protein level).|||basement membrane http://togogenome.org/gene/10090:Arid1b ^@ http://purl.uniprot.org/uniprot/A0A8Q0PK87 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Slco1a4 ^@ http://purl.uniprot.org/uniprot/Q9EP96 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A conserved histidine residue in the third TMD (His-107) may play an essential role in the pH sensitivity of SLCO1A4/OATP1A4-mediated substrate transport.|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Highly expressed in brain and liver. Detected at very low levels in heart and lung.|||Mediates the Na(+)-independent transport of organic anions such as taurocholate, cholate, 17-beta-glucuronosyl estradiol, prostaglandin E2, estrone 3-sulfate, L-thyroxine (T4), the cardiac glycosides ouabain and digoxin and thyroid hormones. Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment. Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions. http://togogenome.org/gene/10090:Pxmp2 ^@ http://purl.uniprot.org/uniprot/P42925|||http://purl.uniprot.org/uniprot/Q5D073 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxisomal membrane protein PXMP2/4 family.|||Interacts with PEX19 and SIVA1.|||Membrane|||Peroxisome membrane|||Seems to be involved in pore-forming activity and may contribute to the unspecific permeability of the peroxisomal membrane. http://togogenome.org/gene/10090:Clca3a1 ^@ http://purl.uniprot.org/uniprot/Q9QX15 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CLCR family.|||Cell membrane|||Glycosylated.|||Highly expressed in skin and spleen, and at lower levels in kidney and liver (PubMed:9822685, PubMed:10072771). Also detected in lung and brain (PubMed:9822685). Not detected in lung or brain (PubMed:10072771). In lung, localizes to respiratory epithelia of the bronchi and trachea and the submucosal glands (PubMed:9822685).|||Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner.|||The 130-kDa product is autoproteolytically processed by the metalloprotease domain and yields two subunits, a 90-kDa protein and a group of 32- to 38-kDa proteins (PubMed:9822685). The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity (By similarity). http://togogenome.org/gene/10090:Svip ^@ http://purl.uniprot.org/uniprot/Q3UZP4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SVIP family.|||Cell membrane|||Golgi apparatus membrane|||Interacts with VCP.|||Membrane|||Smooth endoplasmic reticulum membrane http://togogenome.org/gene/10090:Vps45 ^@ http://purl.uniprot.org/uniprot/P97390 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Endosome membrane|||Golgi apparatus membrane|||Interacts with ZFYVE20 (By similarity). Interacts with STX6.|||May play a role in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network. http://togogenome.org/gene/10090:Cdk2ap1 ^@ http://purl.uniprot.org/uniprot/O35207 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDK2AP family.|||Chromosome|||Homodimer (By similarity). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (By similarity). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (By similarity). Interacts with monomeric unphosphorylated CDK2 (PubMed:10938106). Interacts with CDK2AP2 (By similarity). Interacts with GATAD2A (By similarity). Interacts with HDAC1 (By similarity). Interacts with HDAC2 (By similarity). Interacts with MBD2 (By similarity). Interacts with MBD3 (By similarity). Interacts with RBBP4 (By similarity). Interacts with RBBP7 (By similarity).|||Inhibitor of cyclin-dependent kinase CDK2 (PubMed:10938106). Also acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity).|||Nucleus|||Phosphorylated in vitro by IKBKE at Ser-45. http://togogenome.org/gene/10090:Adipor1 ^@ http://purl.uniprot.org/uniprot/Q3UPA4|||http://purl.uniprot.org/uniprot/Q53YY4|||http://purl.uniprot.org/uniprot/Q91VH1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ADIPOR family.|||Cell membrane|||Detected in brain and quadriceps muscle (at protein level) (PubMed:17327425). Widely expressed (PubMed:12802337). Expressed in heart, kidney, liver, lung, skeletal muscle, white adipose tissue, brown adipose tissue, aorta and spleen (PubMed:12802337, PubMed:24742672). Weakly expressed in brain and testis (PubMed:12802337).|||May form homooligomers and heterooligomers with ADIPOR2 (By similarity). Interacts with APPL2 (via BAR domain); hinders the accessibility of APPL1 to ADIPOR1; negatively regulates adiponectin signaling; ADIPOQ dissociates this interaction and facilitates the recruitment of APPL1 to ADIPOR1 (PubMed:19661063). Interacts with APPL1; ADIPOQ enhances this interaction; inhibites adiponectin-stimulated binding of APPL2 to ADIPOR1 (PubMed:19661063).|||Membrane|||Mutant mice are viable and fertile, but display defects in glucose and lipid homeostasis. The precise phenotype may depend on experimental details and genetic background. Mutant mice have normal body weight, but increased plasma glucose and insulin levels (PubMed:17268472). Mutant male mice, but not female mice, display increased body weight gain on standard chow, in spite of similar food intake as wild-type (PubMed:17327425). Mutant mice display increased body weight, both on standard chow and on high fat and high sucrose diet (PubMed:24742672). Male mice have increased total body fat mass after 15 weeks, and have increased weights of both white and brown adipose tissue (PubMed:17327425, PubMed:24742672). Mutant mice have impaired glucose tolerance (PubMed:24742672). Male mice have decreased glucose tolerance, but no significant change in the insulin response (PubMed:17327425). Female mice display increased fasting glucose levels, but unchanged fasting insulin levels (PubMed:17327425). Male and female mice display increased levels of liver triglycerides relative to wild-type (PubMed:17327425, PubMed:24742672). Male mice display decreased locomotor activity and decreased energy expenditure relative to wild-type (PubMed:17327425). Mutant mice display normal revascularization after chronic limb ischemia caused by severing of blood vessels (PubMed:24742672). Hepatocytes from mice lacking both Adipor1 and Adipor2 show loss of adiponectin binding and lack of adiponectin-mediated activation of AMPK and Ppara (PubMed:17268472). Mice lacking both Adipor1 and Adipor2 display elevated glucose and insulin levels in blood plasma, indicative of glucose intolerance and insulin resistance (PubMed:17268472).|||Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:17327425, PubMed:17268472, PubMed:24742672). Required for normal glucose and fat homeostasis and for maintaining a normal body weight (PubMed:17327425, PubMed:24742672). ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis (PubMed:12802337, PubMed:17327425, PubMed:17268472, PubMed:24742672). Has high affinity for globular adiponectin and low affinity for full-length adiponectin (PubMed:12802337).|||The N-terminus is cytoplasmic and the C-terminus is extracellular, contrary to what is observed for G-protein coupled receptors. Unlike G-protein coupled receptors, transmembrane helices are not kinked or tilted relative to the plane of the membrane. http://togogenome.org/gene/10090:Adgrl4 ^@ http://purl.uniprot.org/uniprot/Q923X1 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Endothelial orphan receptor that acts as a key regulator of angiogenesis.|||Glycosylated.|||Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked.|||Induced by VEGF and FGF2.|||No visible phenotype but deficient mice present increased cardiac hypertrophy in response to pressure overload.|||Proteolytically cleaved into 2 subunits, an extracellular alpha subunit and a seven-transmembrane subunit.|||The transmembrane domain is not required for cleavage, but it is required for dimer formation. http://togogenome.org/gene/10090:Dhcr24 ^@ http://purl.uniprot.org/uniprot/Q8VCH6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAD-binding oxidoreductase/transferase type 4 family.|||Catalyzes the reduction of the delta-24 double bond of sterol intermediates during cholesterol biosynthesis (PubMed:26114596). In addition to its cholesterol-synthesizing activity, can protect cells from oxidative stress by reducing caspase 3 activity during apoptosis induced by oxidative stress. Also protects against amyloid-beta peptide-induced apoptosis (By similarity).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane http://togogenome.org/gene/10090:Prelid1 ^@ http://purl.uniprot.org/uniprot/Q8R107 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in all tissues tested except testis with highest levels in thymus.|||Forms a complex with TRIAP1 in the mitochondrion intermembrane space. Interacts with OPA1 and AIFM1 (By similarity).|||Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. In vitro, the TRIAP1:PRELID1 complex mediates the transfer of phosphatidic acid (PA) between liposomes and probably functions as a PA transporter across the mitochondrion intermembrane space to provide PA for CL synthesis in the inner membrane. Regulates the mitochondrial apoptotic pathway in primary Th cells. Regulates Th cell differentiation by down-regulating STAT6 thereby reducing IL-4-induced Th2 cell number. May be important for the development of vital and immunocompetent organs (By similarity).|||Mitochondrion|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Nkain2 ^@ http://purl.uniprot.org/uniprot/Q4PNJ2 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKAIN family.|||Cell membrane|||Detected in the brain only and specifically in neurons; expressed in multiple regions such as cerebral cortex, thalamus, cerebellum, olfactory bulb and brainstem, but not in the hippocampus.|||Interacts with ATP1B1. http://togogenome.org/gene/10090:Casp2 ^@ http://purl.uniprot.org/uniprot/P29594 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C14A family.|||During embryonic development is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney.|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit. Forms a complex named the PIDDosome with PIDD1 and CRADD. Interacts with NOL3 (via CARD domain); inhibits CASP2 activity in a phosphorylation-dependent manner.|||High level expression seen in the embryonic CNS, liver, lung, kidney, small intestine, and hair follicles of vibrissae. Moderate expression seen in the skin, oral mucosa, skeletal muscle, submandibular gland and thymus. In the adult, it is highly expressed in spleen, lung and kidney. Moderately in the brain, heart, testis, liver. Low levels in the thymus, skeletal muscle, ovary and gut.|||Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:7958843). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (By similarity).|||The CARD domain mediates a direct interaction with CRADD.|||The mature protease can process its own propeptide, but not that of other caspases. http://togogenome.org/gene/10090:Spink10 ^@ http://purl.uniprot.org/uniprot/Q8CAC8 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in epydiymis, in the cauda and corpus. Also expressed in brain.|||Membrane|||Probable serine protease inhibitor. http://togogenome.org/gene/10090:Pax2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J267|||http://purl.uniprot.org/uniprot/P32114 ^@ Developmental Stage|||Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Defects in Pax2 are a cause of developmental defects of the kidney, brain, ear and eye.|||Expressed in the developing embryo excretory and central nervous systems. In the developing excretory system; expressed in the pronephric tubules and extending nephric duct beginning at day 9 gestation. At 10 dpc, detected in the nephric cord, Wolffian duct and also individual pronephric tubules. At 11 dpc, expressed in the branched ureter and the mesenchymal condensations, at 12 dpc, expression seen in the collecting ducts and condensed mesenchymal cells. At 14-17 dpc, expressed in the perimeter of the growing kidney but expression declines in the more developed glomerular crevices, and at later developmental stages expression in the kidney declines. In the developing CNS; initially expressed in the ventricular zone in two compartments of cells on either side of the sulcus limitans and along the entire rhombencephalon and spinal cord, later is restricted to progeny cells that have migrated to specific regions of the intermediate zone. In the eye, expression is restricted to the ventral half of the optic cup and stalk and later to the optic disk and nerve. In the ear, expression is restricted to regions of the otic vesicle that form neuronal components.|||Interacts with ELGN3; the interaction targets PAX2 for destruction. Interacts with TLE4.|||Kidney and nephrogenic rests.|||Nucleus|||Transcription factor that may have a role in kidney cell differentiation. http://togogenome.org/gene/10090:Zbtb22 ^@ http://purl.uniprot.org/uniprot/Q9Z0G7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Chgb ^@ http://purl.uniprot.org/uniprot/P16014|||http://purl.uniprot.org/uniprot/Q3TY66 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chromogranin/secretogranin protein family.|||Secreted|||Secretogranin-1 is a neuroendocrine secretory granule protein, which may be the precursor for other biologically active peptides. http://togogenome.org/gene/10090:Flot1 ^@ http://purl.uniprot.org/uniprot/O08917|||http://purl.uniprot.org/uniprot/Q540I4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the band 7/mec-2 family. Flotillin subfamily.|||Cell membrane|||Endosome|||Expression increases at least 10-fold as 3T3-L1 cells differentiate into adipocytes.|||Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS (By similarity).|||Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS.|||High expression in brain, white adipose tissue, heart muscle, skeletal muscle and lung. Low expression in spleen, liver and testis.|||May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles.|||Melanosome|||Membrane|||Membrane raft|||caveola http://togogenome.org/gene/10090:Hcn1 ^@ http://purl.uniprot.org/uniprot/O88704 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low.|||Belongs to the potassium channel HCN family.|||Cell membrane|||Homotetramer. Heterotetramer with HCN2. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Interacts with KCNE2. Interacts with the SH3 domain of CSK (PubMed:9405696).|||Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli.|||Inhibited by extracellular cesium ions.|||N-glycosylated.|||Predominantly expressed in brain (PubMed:9405696). Highly expressed in apical dendrites of pyramidal neurons in the cortex, in the layer corresponding to the stratum lacunosum-moleculare in the hippocampus and in axons of basket cells in the cerebellum (at protein level) (PubMed:9405696, PubMed:26269648). Expressed in a subset of elongated cells in taste buds (PubMed:11675786).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Cradd ^@ http://purl.uniprot.org/uniprot/O88843 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that associates with PIDD1 and the caspase CASP2 to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis. Also recruits CASP2 to the TNFR-1 signaling complex through its interaction with RIPK1 and TRADD and may play a role in the tumor necrosis factor-mediated signaling pathway.|||Cytoplasm|||Forms a complex named the PIDDosome with PIDD1 and CASP2 (PubMed:22279524). Interacts (via Death domain) with RIPK1 (via Death domain); the interaction is direct. Interacts with TRADD. Interacts with TNFRSF1A (By similarity).|||Nucleus|||The CARD domain mediates a direct interaction with CASP2.|||The Death domain mediates the interaction with PIDD1 and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn probably recruit 7 CASP2 to form the PIDDosome. The Death domain mediates a direct interaction with the Death domain of RIPK1. http://togogenome.org/gene/10090:Mrps17 ^@ http://purl.uniprot.org/uniprot/Q9CQE3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS17 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:P2rx6 ^@ http://purl.uniprot.org/uniprot/E9PY29|||http://purl.uniprot.org/uniprot/O54803|||http://purl.uniprot.org/uniprot/Q149L9 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the P2X receptor family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||N-glycosylated.|||Predominantly expressed in skeletal muscle. Also expressed in lung.|||Receptor for ATP that acts as a ligand-gated ion channel.|||Unlike most P2XRs, P2RX6 does not seem to form homotrimers or heterotrimers. http://togogenome.org/gene/10090:Nhej1 ^@ http://purl.uniprot.org/uniprot/Q3KNJ2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the XRCC4-XLF family. XLF subfamily.|||Chromosome|||DNA repair protein involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:17360556, PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092, PubMed:30017584). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17360556). Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL (By similarity). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:17360556). Associates with XRCC4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (By similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (By similarity). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (By similarity). Binds DNA in a length-dependent manner (By similarity).|||Embryonic stem cells are highly sensitive to ionizing radiation and have intrinsic DNA double-strand break repair defects (PubMed:17360556). In contrast, knockout mice only have a relatively mild phenotype with no growth defects, neuronal cell death or overt immunodeficiency (PubMed:18775323). Mature lymphocyte numbers are slightly decreased, and pro-B lines, while ionizing radiation-sensitive, perform V(D)J recombination at nearly wild-type levels (PubMed:18775323). Mice lacking both Paxx and Nhej1/Xlf show embryonic lethality caused by severe defects in classical non-homologous end joining (NHEJ) (PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092). Mice lacking both Cyren and Nhej1/Xlf show embryonic lethality caused by severe defects in classical non-homologous end joining (NHEJ) (PubMed:30017584).|||Homodimer; mainly exists as a homodimer when not associated with XRCC4. Interacts with XRCC4; the interaction is direct and is mediated via a head-to-head interaction between N-terminal head regions. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL.|||Nucleus|||Phosphorylated by PRKDC at the C-terminus in response to DNA damage. Phosphorylation by PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are highly redundant and regulate ability of the XRCC4-NHEJ1/XLF subcomplex to bridge DNA. Phosphorylation does not prevent interaction with XRCC4 but disrupts ability to bridge DNA and promotes detachment from DNA.|||The Leu-lock (Leu-115) site inserts into a hydrophobic pocket in XRCC4.|||The coiled-coil region mediates homodimerization. http://togogenome.org/gene/10090:Wdr91 ^@ http://purl.uniprot.org/uniprot/Q7TMQ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat WDR91 family.|||Early endosome membrane|||Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport. It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (By similarity). May play a role in meiosis (PubMed:27346680).|||Interacts with WDR81; involved in early to late endosome cargo transport. Interacts with BECN1; negatively regulates the PI3 kinase/PI3K activity associated with endosomal membranes.|||Late endosome membrane http://togogenome.org/gene/10090:Gast ^@ http://purl.uniprot.org/uniprot/P48757 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in the stomach and duodenum. Low levels in brain, ovary and pancreas.|||Belongs to the gastrin/cholecystokinin family.|||Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.|||Secreted|||Sulfation enhances proteolytic processing, and blocks peptide degradation. Levels of sulfation differ between proteolytically-cleaved gastrins and between tissues (By similarity). http://togogenome.org/gene/10090:Camkk2 ^@ http://purl.uniprot.org/uniprot/Q8C078 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin (By similarity).|||Autophosphorylated and phosphorylated by PKA. Each isoform may show a different pattern of phosphorylation.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK4 and CAMK1D (By similarity). Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). May play a role in neurite growth. Isoform 2 may promote neurite elongation, while isoform 1 may promoter neurite branching (By similarity). May be involved in hippocampal activation of CREB1.|||Cytoplasm|||Expressed in all tissues tested. A differential expression pattern compared to CAMKK1 is observed in the brain.|||Interacts with calmodulin.|||Mice are unable to form spatial long-term memory.|||Nucleus|||The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates.|||The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition.|||neuron projection http://togogenome.org/gene/10090:Sult3a1 ^@ http://purl.uniprot.org/uniprot/Q059N0 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Or52k2 ^@ http://purl.uniprot.org/uniprot/E9Q545 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grb7 ^@ http://purl.uniprot.org/uniprot/Q03160 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. Promotes activation of down-stream protein kinases, including STAT3, AKT1, MAPK1 and/or MAPK3. Promotes activation of HRAS. Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration (By similarity). Plays a role in the assembly and stability of RNA stress granules. Binds to the 5'UTR of target mRNA molecules and represses translation of target mRNA species, when not phosphorylated. Phosphorylation impairs RNA binding and promotes stress granule disassembly during recovery after cellular stress.|||Belongs to the GRB7/10/14 family.|||Cell membrane|||Cell projection|||Cytoplasm|||Cytoplasmic granule|||Homodimer. Interacts (via SH2 domain) with EGFR, ERBB2, ERBB3 (when phosphorylated), ERBB4 (when phosphorylated), EPHB1, INSR, FGFR1, PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts with SHC1. Interacts with RND1. Interacts (when tyrosine phosphorylated) with FHL2 and HAX1 (By similarity). Interacts (via SH2 domain) with RET and PTK2/FAK1. Interacts (when not phosphorylated) with ELAVL1. In stressed cells, but not in normal cells, part of a complex that contains at least GRB7, PTK2/FAK1, STAU1, ELAVL1 and TIA1. Interacts (via SH2 domain) with KIT (phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated).|||Phosphorylated on serine and threonine residues in response to activation of receptor kinases. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated on tyrosine residues by PTK2/FAK1, and possibly also other kinases. Phosphorylation is enhanced by activation of receptor kinases. Tyrosine phosphorylation is essential for activation of down-stream protein kinases (By similarity). Phosphorylated on tyrosine residues in response to NTN1 signaling. Phosphorylation promotes stress granule disassembly during recovery after cellular stress.|||The PH domain mediates interaction with membranes containing phosphoinositides.|||focal adhesion http://togogenome.org/gene/10090:Rps10 ^@ http://purl.uniprot.org/uniprot/P63325|||http://purl.uniprot.org/uniprot/Q5M9K7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS10 family.|||Component of the 40S ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the small ribosomal subunit (PubMed:36517592). The methylated form interacts with NPM1 (By similarity).|||Cytoplasm|||Methylated by PRMT5. Methylation is necessary for its interaction with NPS1, its localization in the granular component (GC) region of the nucleolus, for the proper assembly of ribosomes, protein synthesis and optimal cell proliferation.|||Monoubiquitinated by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide. Deubiquitinated by OTUD3 and USP21, antagonizing ZNF598 activity. Deubiquitinated by OTUD1, antagonizing ZNF598 activity and stimulating formation of polysomes: deubiquitination by OTUD1 promotes stability and translation of a subset mRNAs with a high abundance of rare codons can limit the translation rate. Deubiquitinated by USP10.|||nucleolus http://togogenome.org/gene/10090:Cyp2a5 ^@ http://purl.uniprot.org/uniprot/Q80XK1|||http://purl.uniprot.org/uniprot/Q91X75 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Pdzk1ip1 ^@ http://purl.uniprot.org/uniprot/G3UW41|||http://purl.uniprot.org/uniprot/Q9CQH0 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts with PDZK1. Forms a heterodimer with SLC5A2; this interaction enhances SLC5A2 transporter activity over a hundred-fold.|||Membrane http://togogenome.org/gene/10090:Cyp2c70 ^@ http://purl.uniprot.org/uniprot/Q91W64 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in muricholic acid (MCA) synthesis (PubMed:27638959). Hydroxylates at the 6-beta position two major bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) to form alpha-MCA and beta-MCA, respectively (PubMed:27638959). May regulate NR1H4/farnesoid X receptor signaling, as taurine-conjugated MCAs are antagonists of NR1H4. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:27638959).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in liver.|||Microsome membrane http://togogenome.org/gene/10090:Kdm7a ^@ http://purl.uniprot.org/uniprot/Q3UWM4 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9', 'Lys-27' and 'Lys-36' (H3K9me2, H3K27me2, H3K36me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3. Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate.|||Nucleus|||The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2.|||The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2. http://togogenome.org/gene/10090:Lbr ^@ http://purl.uniprot.org/uniprot/Q3U9G9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ERG4/ERG24 family.|||Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis (PubMed:18785926). Plays a critical role in myeloid cell cholesterol biosynthesis which is essential to both myeloid cell growth and functional maturation (PubMed:22140257). Mediates the activation of NADPH oxidases, perhaps by maintaining critical levels of cholesterol required for membrane lipid raft formation during neutrophil differentiation (PubMed:22140257). Anchors the lamina and the heterochromatin to the inner nuclear membrane (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Highly expressed in the testis and lung. Also expressed in the heart, ovary, kidney and liver.|||Interacts with CBX5 (By similarity). Interacts with DNA (By similarity). Interaction with DNA is sequence independent with higher affinity for supercoiled and relaxed circular DNA than linear DNA (By similarity). Interacts with lamin B (By similarity). Interacts with CLNK (PubMed:26009488). Interacts with TMEM147; promoting LBR localization to the nucleus inner membrane (By similarity).|||Nucleus|||Nucleus inner membrane|||Phosphorylated by CDK1 in mitosis when the inner nuclear membrane breaks down into vesicles that dissociate from the lamina and the chromatin (By similarity). It is phosphorylated by different protein kinases in interphase when the membrane is associated with these structures (By similarity). Phosphorylation of LBR and HP1 proteins may be responsible for some of the alterations in chromatin organization and nuclear structure which occur at various times during the cell cycle (By similarity). Phosphorylated by SRPK1 (By similarity). In late anaphase LBR is dephosphorylated, probably by PP1 and/or PP2A, allowing reassociation with chromatin (By similarity).|||Strongly expressed in liver, skin, brain as well as in specific regions of the developing cartilage and bone in embryos.|||The Tudor domain may not recognize methylation marks, but rather bind unassembled free histone H3. http://togogenome.org/gene/10090:Sis ^@ http://purl.uniprot.org/uniprot/F8VQM5 ^@ Caution|||Similarity ^@ Belongs to the glycosyl hydrolase 31 family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Map2k3 ^@ http://purl.uniprot.org/uniprot/O09110|||http://purl.uniprot.org/uniprot/Q5SWN9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Activated by dual phosphorylation on Ser-218 and Thr-222.|||Autophosphorylated. Phosphorylation on Ser-218 and Thr-222 by MAP kinase kinase kinases regulates positively the kinase activity. Phosphorylated by TAOK2.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK. Binds to DYRK1B/MIRK and increases its kinase activity (By similarity). Part of a complex with MAP3K3, RAC1 and CCM2 (PubMed:14634666). Interacts with ARRB1 (By similarity).|||Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. http://togogenome.org/gene/10090:C1ql4 ^@ http://purl.uniprot.org/uniprot/Q4ZJM9 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulated in fasted animals.|||Forms homooligomers, predominantly dimers or trimers. Forms heterooligomers with C1QL1, C1QL2 and C1QL3, when proteins are coexpressed; this interaction does not occur after secretion (PubMed:23449976). Interacts with ADGRB3 (PubMed:21262840).|||Highly expressed in testis and adipose tissue, brown adipose tissue expressing higher levels than subcutaneous and visceral white adipose tissue. In gonadal fat pad, expressed at lower levels in adipocytes than in the stromal vascular fraction (VSP), which contains preadipocytes, fibroblasts, endothelial cells and occasional immune cells. Expression exhibits sexually dimorphism, with higher levels in females than in males.|||May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses. May inhibit adipocyte differentiation at an early stage of the process.|||Secreted http://togogenome.org/gene/10090:Olah ^@ http://purl.uniprot.org/uniprot/Q8R197 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thioesterase family.|||Contributes to the release of free fatty acids from fatty acid synthase (FASN). Has broad substrate specificity, giving rise to a range of free fatty acids with chain lengths between 10 and 16 carbon atoms (C10 - C16).|||Interacts (via C-terminus) with FASN.|||cytosol http://togogenome.org/gene/10090:Znhit2 ^@ http://purl.uniprot.org/uniprot/Q9QY66 ^@ Function|||Subunit|||Tissue Specificity ^@ Interacts (via HIT-type zinc finger) with RUVBL2 in the presence of ATP or ADP; shows a stronger interaction in the presence of ADP.|||Low expression in most tissues; highly expressed in testis; particularly in seminiferous tubules.|||May act as a bridging factor mediating the interaction between the R2TP/Prefoldin-like (R2TP/PFDL) complex and U5 small nuclear ribonucleoprotein (U5 snRNP) (By similarity). Required for the interaction of R2TP complex subunit RPAP3 and prefoldin-like subunit URI1 with U5 snRNP proteins EFTUD2 and PRPF8 (By similarity). May play a role in regulating the composition of the U5 snRNP complex (By similarity). http://togogenome.org/gene/10090:Rhod ^@ http://purl.uniprot.org/uniprot/P97348 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Early endosome|||Interacts with PAK5. Interacts (in GTP-bound form) with DAPK3, FILIP1 and WHAMM. Interacts (independent of GTP-loaded status) with ANKFY1.|||Involved in endosome dynamics. May coordinate membrane transport with the function of the cytoskeleton. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Participates in the reorganization of actin cytoskeleton; the function seems to involve WHAMM and includes regulation of filopodia formation and actin filament bundling. Can modulate the effect of DAPK3 in reorganization of actin cytoskeleton and focal adhesion dissolution.|||Widely expressed. http://togogenome.org/gene/10090:Acsbg2 ^@ http://purl.uniprot.org/uniprot/Q2XU92 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family. Bubblegum subfamily.|||Catalyzes the conversion of fatty acids such as long chain and very long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation. Can activate diverse saturated, monosaturated and polyunsaturated fatty acids. Has increased ability to activate oleic and linoleic acid. May play a role in spermatogenesis.|||Cytoplasm|||Membrane|||Testis- and brainstem-specific. Expressed in pubertal and adult testis. Enriched in germ cells and Sertoli cells while present at a lower level in Leydig cells. Present in testicular Sertoli cells and large motoneurons in the medulla oblongata and cervical spinal cord (at protein level). http://togogenome.org/gene/10090:Map3k10 ^@ http://purl.uniprot.org/uniprot/Q66L42 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Activates the JUN N-terminal pathway.|||Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Homodimer. Interacts with SH3RF2.|||Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation. http://togogenome.org/gene/10090:Trpa1 ^@ http://purl.uniprot.org/uniprot/Q8BLA8 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cytosolic factor (probably pyrophosphate, polytriphosphate, polyP4, polyP25, polyP45, and/or polyP65) is necessary for TRPA1 activation by irritants (PubMed:17567811). Such factor acts by keeping TRPA1 in a agonist-sensitive state (PubMed:17567811). Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079 (PubMed:15843607, PubMed:29703838, PubMed:31447178). Activated by icilin, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), and PF-4840154 (PubMed:17237762, PubMed:29703838).|||Belongs to the transient receptor (TC 1.A.4) family.|||C-terminal helices from the four subunits associate to form atypical coiled coil structure; this region is probably involved in binding the inositol polyphosphates that are required for optimal channel activity (in vitro).|||Cell membrane|||During utricle development, it is first expressed at 15 dpc and 16 dpc and peaks at 17 dpc. It drops at 18 dpc but increases again at 19 dpc, possibly corresponding to a second wave of hair cells that are generated at 15 dpc.|||Expressed in inner ear (at protein level). Specifically expressed in a subset of nociceptive neurons. Expressed in the same neurons that TRPV1. In contrast, it is not expressed in neurons expressing TRPM8. Expressed in the superior cervical ganglion of vagus nerve. Expressed in the inferior ganglion (nodose ganglion) of vagus nerve (PubMed:21873995). Expressed in dorsal root ganglia neurons (PubMed:21873995).|||Homotetramer (PubMed:21908607). Interacts with TMEM100 (PubMed:25640077). Interacts with EGLN1 (PubMed:21873995). Interacts with the scorpion wasabi receptor toxin at the same site that electrophiles but in a non-covalent manner (By similarity).|||Hydroxylation is required for TRPA1 activity inhibition in normoxia. In hypoxia, the decrease in oxygen concentration diminishes the activity of the hydroxylase EGLN1, thus relieving TRPA1 from inhibition and ultimately leading to channel activation.|||Mice display normal cold sensitivity and unimpaired auditory function, suggesting that this channel is not required for the initial detection of noxious cold or sound. However, they exhibit pronounced deficits in bradykinin-evoked nociceptor excitation and pain hypersensitivity.|||Oxidation of Cys-634 and Cys-859 in hyperoxia may override the hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation.|||Receptor-activated non-selective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function (PubMed:24140646). Shows 8-fold preference for divalent over monovalent cations. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of irritants, such as allylthiocyanate (AITC) found in mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an irritant from tears gas and vehicle exhaust fumes (PubMed:16564016). Acts also as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Is activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds. Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner, whereas mechanisms of non-electrophilic ligands are not well determined. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system.|||TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain (PubMed:17237762, PubMed:22207754).|||The ANK repeat domain consists of a convex stem structure followed by a crescent-shaped structure that surrounds the protein core. http://togogenome.org/gene/10090:Slc22a17 ^@ http://purl.uniprot.org/uniprot/Q9D9E0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Cell surface receptor for LCN2 (24p3) that plays a key role in iron homeostasis and transport. Able to bind iron-bound LCN2 (holo-24p3), followed by internalization of holo-24p3 and release of iron, thereby increasing intracellular iron concentration and leading to inhibition of apoptosis. Also binds iron-free LCN2 (apo-24p3), followed by internalization of apo-24p3 and its association with an intracellular siderophore, leading to iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration and resulting in apoptosis.|||Expressed from 7 dpc and throughout development.|||Vacuole membrane|||Widely expressed. http://togogenome.org/gene/10090:Msrb1 ^@ http://purl.uniprot.org/uniprot/Q9JLC3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MsrB Met sulfoxide reductase family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine (PubMed:11929995, PubMed:14699060, PubMed:23911929, PubMed:20605785). While in many cases, methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residue (PubMed:14699060, PubMed:20605785). Acts as a regulator of actin assembly by reducing methionine (R)-sulfoxide mediated by MICALs (MICAL1, MICAL2 or MICAL3) on actin, thereby promoting filament repolymerization (PubMed:23911929). Plays a role in innate immunity by reducing oxidized actin, leading to actin repolymerization in macrophages (PubMed:23911929).|||Nucleus|||Truncated MSRB1/SEPX1 proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(FEM1C) E3 ubiquitin-protein ligase complex.|||cytoskeleton http://togogenome.org/gene/10090:Parpbp ^@ http://purl.uniprot.org/uniprot/A0A0R4J0G5|||http://purl.uniprot.org/uniprot/Q6IRT3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PARI family.|||Cytoplasm|||Expressed in the ovary, Sertoli cells of the testis and in granular cells within the cerebellum.|||Interacts with RAD51 and PCNA. Interacts with PARP1 (By similarity). Interacts with TASOR (PubMed:31112734).|||Nucleus|||Required to suppress inappropriate homologous recombination, thereby playing a central role DNA repair and in the maintenance of genomic stability. Antagonizes homologous recombination by interfering with the formation of the RAD51-DNA homologous recombination structure. Binds single-strand DNA and poly(A) homopolymers. Positively regulate the poly(ADP-ribosyl)ation activity of PARP1; however such function may be indirect (By similarity). http://togogenome.org/gene/10090:Or10ag54 ^@ http://purl.uniprot.org/uniprot/E9PXB8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem87b ^@ http://purl.uniprot.org/uniprot/Q8BKU8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the LU7TM family. TMEM87 subfamily.|||Golgi apparatus membrane|||May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN). http://togogenome.org/gene/10090:E4f1 ^@ http://purl.uniprot.org/uniprot/Q8CCE9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Continuously expressed during embryogenesis.|||Cytoplasm|||Death before 7.5 dpc probably at the peri-implantation stage. Blastocysts display defects in mitotic progression and chromosomal segregation and increased apoptosis.|||Homodimer; binds DNA as a dimer (By similarity). Forms a complex with CDKN2A and TP53. Interacts with HDAC1, HMGA2 and RASSF1 (By similarity). Interactions with TP53, RB1, ANP32A and probably BMI1 and FHL2 regulate E4F1 activity.|||May be sumoylated by UBE2I upon interaction with CDKN2A.|||May function as a transcriptional repressor. May also function as a ubiquitin ligase mediating ubiquitination of chromatin-associated TP53. Functions in cell survival and proliferation through control of the cell cycle. Functions in the p53 and pRB tumor suppressor pathways and regulates the cyclin CCNA2 transcription.|||Phosphorylated; phosphorylation is cell cycle-dependent and regulates DNA-binding activity and function.|||Ubiquitously expressed.|||nucleoplasm http://togogenome.org/gene/10090:Setd4 ^@ http://purl.uniprot.org/uniprot/P58467 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. SETD4 family.|||Histone-lysine N-methyltransferase that acts as a regulator of cell proliferation, cell differentiation and inflammatory response (PubMed:31376731, PubMed:31794893, PubMed:33506343). Regulates the inflammatory response by mediating mono- and dimethylation of 'Lys-4' of histone H3 (H3K4me1 and H3K4me2, respectively), leading to activate the transcription of pro-inflammatory cytokines IL6 and TNF-alpha (PubMed:31376731). Also involved in the regulation of stem cell quiescence by catalyzing the trimethylation of 'Lys-20' of histone H4 (H4K20me3), thereby promoting heterochromatin formation (By similarity). Involved in proliferation, migration, paracrine and myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) (PubMed:33506343).|||No visible phenotype in normal physiological conditions (PubMed:33506343). Increased proliferation of bone marrow mesenchymal stem cells (BMSCs), impaired BMSCs migration and differentiation potentials of lineages of cardiacmyocyte and smooth muscle cell (PubMed:33506343). Conditional deletion in adult mice improves the survival from radiation-induced hematopoietic failure and thymic lymphoma (PubMed:31794893, PubMed:32259569). Extends survival from radiation-induced thymic lymphoma is likely due to slower tumor enlargement in the thymus (PubMed:31794893).|||Nucleus|||cytosol http://togogenome.org/gene/10090:Pdpr ^@ http://purl.uniprot.org/uniprot/Q7TSQ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GcvT family.|||Decreases the sensitivity of PDP1 to magnesium ions, and this inhibition is reversed by the polyamine spermine.|||Heterodimer of a catalytic (PDP1) and a regulatory (PDPR) subunit.|||Mitochondrion matrix http://togogenome.org/gene/10090:Pbdc1 ^@ http://purl.uniprot.org/uniprot/Q9D0B6 ^@ Similarity ^@ Belongs to the PBDC1 family. http://togogenome.org/gene/10090:Ccl25 ^@ http://purl.uniprot.org/uniprot/O35903 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Potentially involved in T-cell development. Recombinant protein shows chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritics cells but is inactive on peripheral blood lymphocytes and neutrophils. Binds to CCR9. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.|||Secreted|||Specifically expressed by thymic dendritic cells. High levels in thymus and small intestine. http://togogenome.org/gene/10090:Aadacl4fm1 ^@ http://purl.uniprot.org/uniprot/Q8BM81 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the 'GDXG' lipolytic enzyme family.|||Membrane http://togogenome.org/gene/10090:Mef2c ^@ http://purl.uniprot.org/uniprot/A0A0G2JEC2|||http://purl.uniprot.org/uniprot/A0A0H2UH28|||http://purl.uniprot.org/uniprot/A0A0H2UKB6|||http://purl.uniprot.org/uniprot/Q3V1B5|||http://purl.uniprot.org/uniprot/Q8CFN5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by p300 on several sites in diffentiating myocytes (By similarity). Acetylation on Lys-4 increases DNA binding and transactivation.|||Belongs to the MEF2 family.|||Expressed in developing endothelial cells and smooth muscle cells, as well as in surrounding mesenchyme, during embryogenesis. Up-regulated during myogenesis.|||Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation, HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with EP300 in differentiating cells; the interaction acetylates MEF2C leading to increased DNA binding and activation (By similarity). Interacts with HDAC7 and CARM1 (PubMed:11279209, PubMed:11713257). Interacts with HDAC4, HDAC7 AND HDAC9; the interaction with HDACs represses transcriptional activity (By similarity). Interacts with LPIN1 (PubMed:19753306). Interacts with MYOCD (PubMed:16818234). Interacts with AKAP13 (PubMed:20139090). Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (PubMed:22956541). Interacts (via N-terminus) with HABP4; this interaction decreases DNA-binding activity of MEF2C in myocardial cells in response to mechanical stress (By similarity). Interacts with JPH2; interaction specifically takes place with the Junctophilin-2 N-terminal fragment cleavage product of JPH2 (PubMed:30409805). Interacts (via MADS box) with SOX18 (PubMed:11554755).|||Mice show impairment in hippocampal-dependent learning and also increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Mice surviving to adulthood manifest smaller, apparently less mature neurons and smaller whole brain size, with resultant aberrant electrophysiology and behavior. Mice exhibit thrombocytopenia and a defect in B-lymphopoiesis.|||Nucleus|||Phosphorylation on Ser-59 enhances DNA binding activity (By similarity). Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity.|||Proteolytically cleaved in cerebellar granule neurons, probably by caspase 7, following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity).|||Sumoylated on Lys-391 with SUMO2 but not by SUMO1 represses transcriptional activity.|||The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.|||Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18 (PubMed:11554755). May also be involved in neurogenesis and in the development of cortical architecture. Isoforms that lack the repressor domain are more active than isoform 1 (By similarity). Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells.|||Widely expressed though mainly restricted to skeletal and cardiac muscle, brain, neurons and lymphocytes. Beta domain-lacking isoforms are the most predominantly expressed in all tissues including skeletal and cardiac muscle and brain. Only brain expresses all isoforms. Expression occurs primarily in the internal granule cell layer of the olfactory bulb, cortex, thalamus, hippocampus and cerebellum. Low levels in the cerebellum and hindbrain. Expressed throughout the cortex, including the frontal and entorhinal cortex, dentate gyrus, and basolateral amygdala. Selectively expressed in B-cells but not in T-cells, and its expression increases as B-cells mature.|||sarcoplasm http://togogenome.org/gene/10090:Dpy30 ^@ http://purl.uniprot.org/uniprot/Q99LT0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the MLL1/MLL complex, involved in the methylation of histone H3 at 'Lys-4', particularly trimethylation. Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. May play some role in histone H3 acetylation. In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and histone H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid. Does not affect ES cell self-renewal. May also play an indirect or direct role in endosomal transport.|||Belongs to the dpy-30 family.|||Homodimer. Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7. Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components MEN1, HCFC1, HCFC2, NCOA6, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin. Interacts with ASH2L. The interaction with ASH2L is direct (By similarity). Interacts with ARFGEF1 (By similarity). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (By similarity).|||Nucleus|||trans-Golgi network http://togogenome.org/gene/10090:Mrpl49 ^@ http://purl.uniprot.org/uniprot/Q9CQ40 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL49 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity). Interacts with OXA1L (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Ina ^@ http://purl.uniprot.org/uniprot/P46660 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Class-IV neuronal intermediate filament that is able to self-assemble. It is involved in the morphogenesis of neurons. It may form an independent structural network without the involvement of other neurofilaments or it may cooperate with NEFL to form the filamentous backbone to which NEFM and NEFH attach to form the cross-bridges (By similarity). May also cooperate with the neuronal intermediate filament protein PRPH to form filamentous networks (PubMed:22723690).|||Forms homodimers (in vitro) (By similarity). Forms heterodimers with NEFL, NEFM or NEFH (in vitro) (By similarity).|||O-glycosylated. http://togogenome.org/gene/10090:Nfe2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Y5|||http://purl.uniprot.org/uniprot/Q07279 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. CNC subfamily.|||Component of the NF-E2 complex essential for regulating erythroid and megakaryocytic maturation and differentiation. Binds to the hypersensitive site 2 (HS2) of the beta-globin control region (LCR). This subunit (NFE2) recognizes the TCAT/C sequence of the AP-1-like core palindrome present in a number of erythroid and megakaryocytic gene promoters. Requires MAFK or other small MAF proteins for binding to the NF-E2 motif. May play a role in all aspects of hemoglobin production from globin and heme synthesis to procurement of iron.|||Cytoplasm|||Homodimer; can bind DNA as a homodimer (By similarity). Erythroid transcription activator nuclear factor erythroid-derived 2 (NF-E2), composed of a heterodimer of NFE2 and MAFK, possesses transactivation activity on beta-globin. Also forms high affinity heterodimer with MAFG; the interaction promotes erythropoiesis. Interacts (via the PXY motif 1) with ITCH (via the WW 1 domain); the interaction promotes 'Lys63'-linked ubiquitination of NFE2, translocates it to the cytoplasm and inhibits its transactivation activity. Interacts with KMT2D/MLL2; the interaction promotes transactivation of the beta-globin locus. Interacts with MAPK8 (phosphorylated form); the interaction leads to phosphorylation of NFE2 in undifferentiated cells.|||PML body|||Phosphorylated on serine residues. In undifferentiated erythrocytes, phosphorylated by MAPK8 which then leads to ubiquitination and protein degradation (By similarity).|||Sumoylated. Sumoylation is required for translocation to nuclear bodies PODs, anchoring to the gene loci, and transactivation of the beta-globin gene (By similarity).|||The PXY motifs are required for binding WW domains. PXY1 is required to promote transactivation of beta-globin and for hyperacetylation of histone H3, but not for binding to the HS2 promoter site.|||Ubiquitinated mainly by 'Lys63'-linked ubiquitin (By similarity). Polyubiquitination with 'Lys63'-linked ubiquitin by ITCH retains NFE2 in the cytoplasm preventing its transactivation activity (By similarity). In undifferentiated erythrocyte, ubiquitinated after MAPK8-mediatd phosphorylation leading to protein degradation. http://togogenome.org/gene/10090:Clec2l ^@ http://purl.uniprot.org/uniprot/P0C7M9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Abtb1 ^@ http://purl.uniprot.org/uniprot/Q99LJ2 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||May act as a mediator of the PTEN growth-suppressive signaling pathway. May play a role in developmental processes (By similarity). http://togogenome.org/gene/10090:Micall1 ^@ http://purl.uniprot.org/uniprot/Q8BGT6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Homooligomer (Probable). Interacts (via NPF1 motif) with EHD1 (via EH domain); the interaction is direct and probably recruits EHD1 to membranes. Interacts with EHD3 (via EH domain). Interacts with RAB35 (GTP-bound form); the interaction is direct and probably recruits MICALL1 to membranes. Interacts with ACAP2; the interaction is indirect through RAB35. Interacts with RAB8A (GTP-bound form); regulates RAB8A association with recycling endosomes. Interacts with RAB13 (GTP-bound form). Interacts with ARF6 (GTP-bound form). Interacts with PACSIN2 (via the SH3 domain). Interacts with DPYSL2.|||Late endosome membrane|||Probable lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, may act as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation. May be involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking. Alternatively, may regulate slow endocytic recycling of endocytosed proteins back to the plasma membrane. May indirectly play a role in neurite outgrowth.|||Probably exists in a closed and an opened conformation due to interaction of the C-terminal RAB-binding domain (RBD), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, with the N-terminal calponin-homology (CH) domain. The conformational change is regulated by RAB13 and may modulate MICALL1 interactions with functional partners (By similarity).|||Recycling endosome membrane http://togogenome.org/gene/10090:4930522H14Rik ^@ http://purl.uniprot.org/uniprot/Q9CPZ3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Adra1a ^@ http://purl.uniprot.org/uniprot/P97718|||http://purl.uniprot.org/uniprot/Q8BUE5|||http://purl.uniprot.org/uniprot/Q8BXZ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1A sub-subfamily.|||Cell membrane|||Cytoplasm|||Homo- and heterooligomer. Heterooligomerizes with ADRA1B homooligomers in cardiac myocytes. Interacts with CAVIN4.|||Membrane|||Nucleus membrane|||This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes (By similarity).|||caveola http://togogenome.org/gene/10090:Znhit6 ^@ http://purl.uniprot.org/uniprot/Q3UFB2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the BCD1 family.|||Interacts with FBL, SNU13, NOP58, NUFIP1, RUVBL1, RUVBL2 and TAF9 (By similarity). Interacts (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the presence of ADP (By similarity).|||Required for box C/D snoRNAs accumulation involved in snoRNA processing, snoRNA transport to the nucleolus and ribosome biogenesis. http://togogenome.org/gene/10090:Ankrd34c ^@ http://purl.uniprot.org/uniprot/B2RPW9|||http://purl.uniprot.org/uniprot/Q8BLB8 ^@ Similarity ^@ Belongs to the ANKRD34 family. http://togogenome.org/gene/10090:Prdm15 ^@ http://purl.uniprot.org/uniprot/E9Q8T2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in embryonic stem cells (ESCs) (at protein level).|||Mice die before birth and show early postimplantation developmental defect. Display reduced embryonic stem cells (ESCs) proliferation and self-renewal capacity. Show altered transcription of naive pluripotency and self-renewal modulator genes.|||Nucleus|||Sequence-specific DNA-binding transcriptional regulator. Plays a role as a molecular node in a transcriptional network regulating embryonic development and cell fate decision. Stimulates the expression of upstream key transcriptional activators and repressors of the Wnt/beta-catenin and MAPK/ERK pathways, respectively, that are essential for naive pluripotency and self-renewal maintenance of embryonic stem cells (ESCs). Specifically promotes SPRY1 and RSPO1 transcription activation through recognition and direct binding of a specific DNA sequence in their promoter regions. Also plays a role in induced pluripotent stem cells (iPSCs) reprogramming. Involved in early embryo development. http://togogenome.org/gene/10090:Arhgap10 ^@ http://purl.uniprot.org/uniprot/Q6Y5D8 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Endosome membrane|||GTPase-activating protein that catalyzes the conversion of active GTP-bound Rho GTPases to their inactive GDP-bound form, thus suppressing various Rho GTPase-mediated cellular processes (PubMed:11238453). Also converts Cdc42 to an inactive GDP-bound state (By similarity). Essential for PTKB2 regulation of cytoskeletal organization via Rho family GTPases (PubMed:11238453). Inhibits PAK2 proteolytic fragment PAK-2p34 kinase activity and changes its localization from the nucleus to the perinuclear region. Stabilizes PAK-2p34 thereby increasing stimulation of cell death (PubMed:15471851). Associates with MICAL1 on the endosomal membrane to promote Rab8-Rab10-dependent tubule extension. After dissociation with MICAL1, recruits WDR44 which connects the endoplasmic reticulum (ER) with the endosomal tubule, thereby participating in the export of a subset of neosynthesized proteins (By similarity).|||High levels of expression in brain, testes, liver, heart and kidney.|||Interacts with PKN3 (By similarity). Interacts with caspase-activated PAK2 proteolytic fragment PAK-2p34; the interaction does not affect ARHGAP10 GTPase activation activity towards RHOA and CDC42 (PubMed:15471851). Interacts via its SH3 domain with PTK2/FAK1. Interacts with PTK2B/PYK2; the interaction negatively regulates ARHGAP10 GTPase-activating activity (PubMed:11238453). Interacts with MICAL1 and WDR44; complex formation might transit from GRAF2/ARHGAP10-MICAL1 to GRAF2/ARHGAP10-WDR44 complexes (By similarity).|||Phosphorylated on tyrosine residues, probably involving PTK2B/PYK2.|||The BAR domain is important to associate RAB8A (or RAB8B) and RAB10 to endosomal membrane to promote tubule extension. The BAR domain is also important to recruit WDR44 to endosomal tubules.|||perinuclear region http://togogenome.org/gene/10090:Tecta ^@ http://purl.uniprot.org/uniprot/O08523 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3 products of tectorin seem to exist: HMM, MMM and LMM. They may be generated by active processing or the result of proteolysis occurring between intrachain disulfide bonds.|||Cell membrane|||Cochlea-specific.|||May form homomeric filament after self-association or heteromeric filament after association with beta-tectorin (Probable). Interacts with CEACAM16 (PubMed:25080593).|||One of the major non-collagenous components of the tectorial membrane (By similarity). The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals.|||The presence of a hydrophobic C-terminus preceded by a potential cleavage site strongly suggests that tectorins are synthesized as glycosylphosphatidylinositol-linked, membrane-bound precursors. Tectorins are targeted to the apical surface of the inner ear epithelia by the lipid and proteolytically released into the extracellular compartment.|||Zona pellucida domain may enable to form filaments.|||extracellular matrix http://togogenome.org/gene/10090:Exph5 ^@ http://purl.uniprot.org/uniprot/Q0VAV2 ^@ Function|||Subunit ^@ Interacts with RAB27A.|||May act as Rab effector protein and play a role in vesicle trafficking. http://togogenome.org/gene/10090:C1qc ^@ http://purl.uniprot.org/uniprot/Q02105 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ C1 is a calcium-dependent trimolecular complex of C1q, R and S in the molar ration of 1:2:2. C1q subcomponent is composed of nine subunits, six of which are disulfide-linked dimers of the A and B chains, and three of which are disulfide-linked dimers of the C chain.|||C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.|||Hydroxylation on proline residues within the sequence motif, GXPG, is most likely to be 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.|||Secreted http://togogenome.org/gene/10090:Washc1 ^@ http://purl.uniprot.org/uniprot/Q8VDD8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:19922875). Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration (PubMed:22114305). In T-cells involved in endosome-to-membrane recycling of receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T-cell proliferation and effector function (PubMed:23275443). In dendritic cells involved in endosome-to-membrane recycling of major histocompatibility complex (MHC) class II probably involving retromer and subsequently allowing antigen sampling, loading and presentation during T-cell activation (PubMed:24886983). Involved in cytokinesis and following polar body extrusion during oocyte meiotic maturation (PubMed:24998208). Involved in Arp2/3 complex-dependent actin assembly driving Salmonella typhimurium invasion independent of ruffling (PubMed:19732055). Involved in the exocytosis of MMP14 leading to matrix remodeling during invasive migration and implicating late endosome-to-plasma membrane tubular connections and cooperation with the exocyst complex (By similarity). Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (PubMed:23974797).|||Belongs to the WASH1 family.|||Component of the WASH core complex also described as WASH regulatory complex SHRC composed of WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5. The WASH core complex associates with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex. Interacts (via WHD1 region) with WASHC2; the interaction is direct (By similarity). Interacts with BECN1; WASHC1 and AMBRA1 can competitively interact with BECN1 (PubMed:23974797). Interacts with BLOC1S2; may associate with the BLOC-1 complex. Interacts with tubulin gamma chain (TUBG1 or TUBG2) (PubMed:20308062). Interacts with TBC1D23 (PubMed:29084197).|||Early endosome membrane|||Recycling endosome membrane|||The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro.|||Ubiquitinated at Lys-219 via 'Lys-63'-linked ubiquitin chains by the TRIM27:MAGEL2 E3 ubiquitin ligase complex, leading to promote endosomal F-actin assembly.|||Ubiquitously expressed.|||autophagosome|||centriole http://togogenome.org/gene/10090:Cacna1e ^@ http://purl.uniprot.org/uniprot/A0A087WS83 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.|||Membrane|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. http://togogenome.org/gene/10090:Map2k7 ^@ http://purl.uniprot.org/uniprot/Q8CE90 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. Isoforms 3 and 4 have lower basal activity but a higher level of inducible activation, than isoforms 2, 6, 7 and 8.|||Activated by phosphorylation on Ser-287 and Thr-291 by MAP kinase kinase kinases (MAP3Ks).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Cytoplasm|||Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074).|||Expressed at high levels in brain, lung, liver, skeletal muscle, kidney, and testis and at lower levels in the heart and spleen.|||Expressed at high levels in the brain, spinal cord, eyes, muscle, lungs, vertebrae, and intestine and at lower levels in the heart and livers at 12.5 dpc. At later stages of embryogenesis (14.5 dpc, 16.5 dpc, and 18.5 dpc) high levels were found in the brain, retina, bone marrow, skin, intestine, lung epithelium and the epithelial layers lining the olfactory cavity and developing teeth and whiskers.|||Interacts with RASSF7, the interaction promotes phosphorylation. Interacts with VRK2 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity). Interacts with SH3RF1, MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642). Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103).|||Nucleus|||The D domain (residues 37-73) contains a conserved docking site and is required for the binding to MAPK substrates.|||The DVD domain (residues 393-413) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation. http://togogenome.org/gene/10090:Hhipl2 ^@ http://purl.uniprot.org/uniprot/Q9D2G9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the HHIP family.|||Secreted http://togogenome.org/gene/10090:Pdhx ^@ http://purl.uniprot.org/uniprot/Q8BKZ9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2-oxoacid dehydrogenase family.|||Delipoylated at Lys-97 by SIRT4, delipoylation decreases the PHD complex activity.|||Mitochondrion matrix|||Part of the inner core of the multimeric pyruvate dehydrogenase complex that is composed of about 48 DLAT and 12 PDHX molecules. This core binds multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). Interacts with SIRT4. Interacts with DLD.|||Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex (By similarity). http://togogenome.org/gene/10090:Obox7 ^@ http://purl.uniprot.org/uniprot/Q4KL20 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ddx17 ^@ http://purl.uniprot.org/uniprot/Q3U741|||http://purl.uniprot.org/uniprot/Q501J6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at lysine residues stabilizes the protein, stimulates interaction with HDAC1 and HDAC3, but not HDAC2, and represses ESR1 and TP53 coactivation activity.|||As an RNA helicase, unwinds RNA and alters RNA structures through ATP binding and hydrolysis. Involved in multiple cellular processes, including pre-mRNA splicing, alternative splicing, ribosomal RNA processing and miRNA processing, as well as transcription regulation. Regulates the alternative splicing of exons exhibiting specific features. This function requires the RNA helicase activity. Affects NFAT5 and histone macro-H2A.1/MACROH2A1 alternative splicing in a CDK9-dependent manner. Affects splicing of mediators of steroid hormone signaling pathway, including kinases that phosphorylates ESR1 and transcriptional regulators. By acting splicing of regulatory factors, participates in ESR1 and AR stabilization. Promotes the inclusion of specific AC-rich alternative exons in CD44 transcripts. In myoblasts and epithelial cells, cooperates with HNRNPH1 to control the splicing of specific subsets of exons. In addition to binding mature mRNAs, also interacts with certain pri-microRNAs, including MIR132/miR-132, and stabilizes the primary transcript. Also participates in the MIR132 processing, resulting in significantly higher levels of mature MIR132 than MIR212 despite the fact that both are cotranscribed and co-regulated (PubMed:26947125). Binding of pri-microRNAs may occur on the 3' segment flanking the stem loop via the 5'-[ACG]CAUC[ACU]-3' consensus sequence (By similarity). Participates in MYC down-regulation at high cell density through the production of MYC-targeting microRNAs. Along with DDX5, may be involved in the processing of the 32S intermediate into the mature 28S rRNA. Promoter-specific transcription regulator, functioning as a coactivator or corepressor depending on the context of the promoter and the transcriptional complex in which it exists. Enhances NFAT5 transcriptional activity. Synergizes with TP53 in the activation of the MDM2 promoter; this activity requires acetylation on lysine residues. May also coactivate MDM2 transcription through a TP53-independent pathway. Coactivates MMP7 transcription. Along with CTNNB1, coactivates MYC, JUN, FOSL1 and cyclin D1/CCND1 transcription. Alone or in combination with DDX5 and/or SRA1 non-coding RNA, plays a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling leading to coactivation of MYOD1-dependent transcription. This helicase-independent activity is required for skeletal muscle cells to properly differentiate into myotubes (PubMed:17011493). During epithelial-to-mesenchymal transition, coregulates SMAD-dependent transcriptional activity, directly controlling key effectors of differentiation, including miRNAs which in turn directly repress its expression. Plays a role in estrogen and testosterone signaling pathway at several levels. Mediates the use of alternative promoters in estrogen-responsive genes and regulates transcription and splicing of a large number of steroid hormone target genes. Contrary to the splicing regulation activity, transcriptional coregulation of the estrogen receptor ESR1 is helicase activity-independent. Plays a role in innate immunity. Specifically restricts bunyavirus infection, including Rift Valley fever virus (RVFV) or La Crosse virus (LACV), but not vesicular stomatitis virus (VSV), in an interferon- and DROSHA-independent manner. Binds to RVFV RNA, likely via structured viral RNA elements (By similarity). Promotes mRNA degradation mediated by the antiviral zinc-finger protein ZC3HAV1, in an ATPase-dependent manner (By similarity).|||Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.|||Interacts with DDX5 in an RNA-independent manner (By similarity). Interacts with CDK9 transcription elongation complex under basal conditions. Following cell stimulation with poly(I:C), a synthetic double-stranded RNA mimicking viral infection, the interaction with CDK9 is decreased (By similarity). Interacts with ESR1 in an estrogen-independent manner (By similarity). Interacts with HNRNPH1; this interaction is important for the regulation of alternative splicing on G-quadruplex structures (By similarity). At high, but not low, cell density, interacts with DROSHA and DGCR8, the core components of the microprocessor complex involved in the maturation of primary microRNAs (pri-miRNAs) into pre-miRNAs. The interaction with DGCR8 is reduced during mitosis. At low, but not high, cell density, interacts with YAP1 and with its paralog, WWTR1/TAZ. Interactions with DROSHA and YAP1 are mutually exclusive. In vitro, the pre-miRNA processing activity of the DDX17-containing microprocessor complex is weaker than that of the DROSHA/DGCR8 microprocessor complex (By similarity). Interacts with UPF3B (By similarity). Interacts with NFAT5; this interaction leads to DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-mediated DDX17-enhanced transactivation (By similarity). Interacts with HDAC1, HDAC2 and HDAC3; this interaction with HDAC1 and HDAC3, but not HDAC2, depends upon DDX17 acetylation (By similarity). Interacts with ZC3HAV1 (via N-terminal domain) in an RNA-independent manner. Interacts with EXOSC3/RRP40 and EXOSC5/RRP46; this interaction may be indirect and mediated by ZC3HAV1-binding (By similarity). Interacts with EP300; this interaction leads to acetylation at lysine residues (By similarity). Interacts with CREBBP/CBP and KAT2B/P/CAF (By similarity). Directly interacts with CTNNB1 (By similarity). Interacts with MYOD1 (PubMed:17011493). Interacts with TP53 (By similarity). Interacts with DCP1A in an RNA-independent manner. Interacts with DCP2 in an RNA-dependent manner (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (By similarity). Interacts with ERCC6 (By similarity).|||Nucleus|||Sumoylation significantly increases stability. It also promotes interaction specifically with HDAC1 (but not HDAC2, nor HDAC3) and strongly stimulates ESR1 and TP53 coactivation.|||cytosol|||nucleolus http://togogenome.org/gene/10090:Kif2b ^@ http://purl.uniprot.org/uniprot/A2RSC8|||http://purl.uniprot.org/uniprot/Q8C0N1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. MCAK/KIF2 subfamily.|||Phosphorylation at Thr-125 by PLK1 is required for activity in the correction of kinetochore-microtubules attachment errors, while phosphorylation at Ser-204 also by PLK1 is required for the kinetochore localization and activity in prometaphase.|||Plus end-directed microtubule-dependent motor required for spindle assembly and chromosome movement during mitosis. Has microtubule depolymerization activity. Plays a role in chromosome congression.|||centrosome|||kinetochore|||spindle http://togogenome.org/gene/10090:Tasor ^@ http://purl.uniprot.org/uniprot/Q69ZR9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TASOR family.|||Chromosome|||Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2. Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (By similarity). Plays a crucial role in early embryonic development (PubMed:31112734, PubMed:24781204, PubMed:28839193). Involved in the organization of spindle poles and spindle apparatus assembly during zygotic division (PubMed:31112734). Plays an important role in maintaining epiblast fitness or potency (PubMed:28839193).|||Component of the HUSH complex; at least composed of TASOR, PPHLN1 and MPHOSPH8 (By similarity). Interacts with MORC2; the interaction associateS MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci (By similarity). Interacts with ZNF638; leading to recruitment of the HUSH complex to unintegrated retroviral DNA (By similarity). Interacts with INPP5A, EML1, SV1L, GPSM2, ITGB3BP, CNTN1, ETFA, PSMD8, S100A10, MPHOSPH8, TMEM100, ALB, PARPBP, HCFC2, NCBP1 and SETDB1 (PubMed:31112734).|||Embryonic lethality with robust developmentally delayed phenotype observed at 8.5 dpc, progressing through 9.5 dpc with full lethality by 12.5 dpc (PubMed:24781204, PubMed:28839193). RNAi-mediated knockdown in zygotes results in formation of multipolar spindles and increased ratio of arrested or incorrectly developed embryos (PubMed:28839193).|||Expressed in the epiblast at 5.5 dpc, expression extends into the extraembryonic ectoderm at 6.5 dpc, and at 7.5 dpc expressed in embryonic ectoderm, allantois, amnion and chorion. From 8.5 to 9.5 dpc, ubiquitously expressed in the developing embryo.|||Nucleus|||Present in skin, brain and testis (at protein level) (PubMed:24781204). Ubiquitously expressed at low levels in the majority of the organs, expressed at higher levels in kidneys, spleen, thymus, seminal vesicles, uterus, and ovaries and its expression is almost six times higher in male tissues than in females (PubMed:31112734). Highly expressed in seminiferous tubules with a strong signal in Sertoli cells, spermatogonia, and spermatocytes (PubMed:31112734). http://togogenome.org/gene/10090:Fbxl21 ^@ http://purl.uniprot.org/uniprot/Q8BFZ4 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the hypothalamus, especially in the suprachiasmatic nucleus (SCN). Expression is driven by the core-clock. There is a pronounced diurnal and circadian expression rhythms rising rapidly at the start of the day and declining at the onset of the night.|||Mice show normal periodicity of wheel-running rhythms with compromised organization of daily activities: mice do not display significant difference from their wild-type littermates in both the free-running period in constant darkness (DD) and activity onset in 12 hours of light/12 hours of darkness (LD). However, an alteration in the daily activities is observed: while wild-type mice show 2 peaks of activity during the active period, the late night activity is eliminated in Fbxl21-deficient mice. Mice lacking both Fbxl3 and Fbxl21 show an attenuated phenotype in behavioral rhythm compared to Fbxl3-deficient mice; however, they exhibit unstable behavioral rhythms, sometimes eliciting arrhythmicity.|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL21) composed of CUL1, SKP1, RBX1 and FBXL21. Interacts with CRY1 and CRY2.|||Substrate-recognition component of the SCF(FBXL21) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL21) complex mainly acts in the cytosol and mediates ubiquitination of CRY proteins (CRY1 and CRY2), leading to CRY proteins stabilization. The SCF(FBXL21) complex counteracts the activity of the SCF(FBXL3) complex and protects CRY proteins from degradation. Involved in the hypothalamic suprachiasmatic nucleus (SCN) clock regulating temporal organization of the daily activities.|||The mechanism by which the SCF(FBXL21) complex stabilizes CRY proteins (CRY1 and CRY2) is still unclear: according to a report, the SCF(FBXL21) complex does not catalyze 'Lys-48'-linked polyubiquitin chains, but catalyzes a different type of ubiquitin chains that do not lead to degradation (PubMed:23452856). According to a second report, FBXL21 has a higher affinity for CRY proteins compared to FBXL3, while the SCF(FBXL21) complex has weaker ubiquitin-ligase activity compared to the SCF(FBXL3) complex: as a consequence, the SCF(FBXL21) complex protects CRY proteins from SCF(FBXL3) activity and degradation in the nucleus, while it promotes slow degradation of CRY proteins in the cytosol (PubMed:23452855).|||cytosol http://togogenome.org/gene/10090:Ier2 ^@ http://purl.uniprot.org/uniprot/P17950 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IER family.|||By growth factors and cycloheximide.|||Cytoplasm|||DNA-binding protein that seems to act as a transcription factor (By similarity). Involved in the regulation of neuronal differentiation, acts upon JNK-signaling pathway activation and plays a role in neurite outgrowth in hippocampal cells (By similarity). May mediate with FIBP FGF-signaling in the establishment of laterality in the embryo (By similarity). Promotes cell motility, seems to stimulate tumor metastasis (By similarity).|||Nucleus http://togogenome.org/gene/10090:Npm1 ^@ http://purl.uniprot.org/uniprot/Q5BL09|||http://purl.uniprot.org/uniprot/Q5SQB7|||http://purl.uniprot.org/uniprot/Q61937|||http://purl.uniprot.org/uniprot/Q9DAY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated.|||Acetylated at C-terminal lysine residues, thereby increasing affinity to histones.|||Belongs to the nucleoplasmin family.|||Decamer formed by two pentameric rings associated in a head-to-head fashion. Disulfide-linked dimers under certain conditions. Interacts with NSUN2 and SENP3 (By similarity). The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with the methylated form of RPS10. Interacts (via N-terminal domain) with APEX1; the interaction is RNA-dependent and decreases peroxide-damaged cells. Interacts with NEK2. Interacts with ROCK2 and BRCA2 (By similarity). Interacts with RPGR. Interacts with CENPW (By similarity). Interacts with EIF2AK2/PKR. Interacts with DDX31; this interaction prevents interaction between NPM1 and HDM2 (By similarity). Interacts with MYC; competitive with NOP53. Interacts with NOP53; the interaction is direct and competitive with MYC (By similarity). Interacts with LRRC34 (PubMed:24991885). Interacts with RRP1B (By similarity). Interacts with NPM3 (By similarity). Interacts with ALKBH2. Interacts with TTF1 (via C-terminal region) (PubMed:20513429).|||Expressed in B-cells that have been induced to switch to various Ig isotypes.|||Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade. In complex with MYC enhances the transcription of MYC target genes. May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (PubMed:20513429).|||Phosphorylated at Ser-4 by PLK1 and PLK2. Phosphorylation at Ser-4 by PLK2 in S phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at Ser-4 by PLK1 takes place during mitosis. Phosphorylated by CDK2 at Ser-125 and Thr-198. Phosphorylation at Thr-198 may trigger initiation of centrosome duplication. Phosphorylated by CDK1 at Thr-198, Thr-217, Thr-232 and Thr-235 during cell mitosis. When these four sites are phosphorated, RNA-binding activity seem to be abolished. May be phosphorylated at Ser-70 by NEK2. The Thr-198 phosphorylated form has higher affinity for ROCK2 (By similarity).|||Sumoylated by ARF.|||Ubiquitinated. Ubiquitination leads to proteasomal degradation. Deubiquitinated by USP36.|||centrosome|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Tas2r107 ^@ http://purl.uniprot.org/uniprot/Q7M725 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors with distinct ligand specificities are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Npy5r ^@ http://purl.uniprot.org/uniprot/O70342|||http://purl.uniprot.org/uniprot/Q543U8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders (By similarity).|||Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders. http://togogenome.org/gene/10090:Mta2 ^@ http://purl.uniprot.org/uniprot/Q9R190 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:10444591, PubMed:27806305). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:27806305). Interacts with CHD3 (By similarity). Interacts with CHD4 (By similarity). Interacts with GATAD2A (By similarity). Interacts with HDAC7 (PubMed:10984530). Interacts with MBD3 (PubMed:12124384). Interacts with p53/TP53 (By similarity). Interacts with MINT (By similarity). Interacts with PIMREG (By similarity). Interacts with NACC2 (By similarity). Interacts with ERCC6 (By similarity). Interacts with PWWP2B (PubMed:34180153).|||May function as a transcriptional coregulator (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or51a10 ^@ http://purl.uniprot.org/uniprot/Q924X8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Reps1 ^@ http://purl.uniprot.org/uniprot/O54916 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Due to intron retention.|||EGF stimulates phosphorylation on Tyr-residues.|||Expressed in all tissues examined. The highest level expression was found in the kidney and testis.|||Homodimer (Potential). Interacts with RALBP1, CRK and GRB2. Binding to RALBP1 does not affect its Ral-binding activity. Forms a complex with the SH3 domains of CRK and GRB2 which may link it to an EGF-responsive tyrosine kinase. Interacts with RAB11FIP2 (By similarity). Interacts with AMPH, ITSN1 (via SH3 domains) and SGIP1; may be involved in clathrin-mediated endocytosis (By similarity).|||May coordinate the cellular actions of activated EGF receptors and Ral-GTPases.|||clathrin-coated pit http://togogenome.org/gene/10090:Cmtm4 ^@ http://purl.uniprot.org/uniprot/Q8CJ61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a backup for CMTM6 to regulate plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. May protect PD-L1/CD274 from being polyubiquitinated and targeted for degradation.|||Belongs to the chemokine-like factor family.|||Interacts with PD1L1 and CMTM6.|||Membrane http://togogenome.org/gene/10090:Or5g26 ^@ http://purl.uniprot.org/uniprot/Q9QY00 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Ing4 ^@ http://purl.uniprot.org/uniprot/Q8C0D7 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ING family.|||Citrullination by PADI4 within the nuclear localization signal disrupts the interaction with p53 and increases susceptibility to degradation.|||Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Through chromatin acetylation it may function in DNA replication. May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation. Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA. May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC. Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1) (By similarity). Can enhance apoptosis induced by serum starvation in mammary epithelial cell line HC11 (PubMed:11888890).|||Expressed in the mammary gland, ovary, spleen and muscle.|||Homodimer. Component of the HBO1 complex composed of KAT7/HBO1, MEAF6, ING4 or ING5, and one scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE scaffold (JADE1, JADE2 and JADE3) mediate acetylation of histone H4. Interacts with H3K4me3 and to a lesser extent with H3K4me2, the interaction augments KAT7/HBO1 acetylation activity on H3 tails. Interacts with EP300, RELA and TP53; these interactions may be indirect. Interacts with EGLN1.|||Interacts with BCL2A1.|||Isoform 2, isoform 3, isoform 4 and isoform 5 are expressed in the mammary gland, ovary, spleen and muscle.|||May be due to a competing acceptor splice site.|||May be due to a competing donor splice site.|||May be due to intron retention.|||Nucleus|||The N-terminal coiled-coil domain mediates homodimerization.|||The PHD-type zinc finger mediates the binding to H3K4me3. http://togogenome.org/gene/10090:Nmb ^@ http://purl.uniprot.org/uniprot/D3Z621|||http://purl.uniprot.org/uniprot/Q9CR53 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the bombesin/neuromedin-B/ranatensin family.|||During osteoclast development, expression increases as the cells differentiate with high expression levels in mature osteoclasts (at protein level).|||In the hindbrain, expressed in the medulla surrounding the lateral half of the facial nucleus (PubMed:26855425). Also expressed in the olfactory bulb and hippocampus (PubMed:26855425). Detected in a subset of neurons distributed throughout the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) (PubMed:26855425). Within the RTN/pFRG, expressed in neuronal subpopulations distinct from those expressing Grp (PubMed:26855425). Expressed in lung (PubMed:31601264).|||Secreted|||Significant reduction in the sneezing response to capsaicin at both low and high doses but does not affect pain-related nose wiping behavior or apnea induced by capsaicin (PubMed:34133943). Abolishes the sneezing response to histamine, seratonin and the neuropeptide Npff (PubMed:34133943). Abolishes sneezing response to mast cell-dependent allergy (PubMed:34133943).|||Stimulates smooth muscle contraction (By similarity). Induces sighing by acting directly on the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity (PubMed:26855425). Contributes to the induction of sneezing following exposure to chemical irritants or allergens which causes release of NMB by nasal sensory neurons and activation of NMBR-expressing neurons in the sneeze-evoking region of the brainstem (PubMed:34133943). These in turn activate neurons of the caudal ventral respiratory group, giving rise to the sneeze reflex (PubMed:34133943). Contributes to induction of acute itch, possibly through activation of the NMBR receptor on dorsal root ganglion neurons (PubMed:30734045). Increases expression of NMBR and steroidogenic mediators STAR, CYP11A1 and HSD3B1 in Leydig cells, induces secretion of testosterone by Leydig cells and also promotes Leydig cell proliferation (By similarity). Plays a role in the innate immune response to influenza A virus infection by enhancing interferon alpha expression and reducing expression of IL6 (PubMed:31601264). Plays a role in CSF1-induced proliferation of osteoclast precursors by contributing to the positive regulation of the expression of the CSF1 receptor CSF1R (PubMed:28780306).|||Up-regulated in lung tissue in response to infection with influenza A virus.|||neuron projection http://togogenome.org/gene/10090:Pik3cd ^@ http://purl.uniprot.org/uniprot/O35904|||http://purl.uniprot.org/uniprot/Q3T9Y0|||http://purl.uniprot.org/uniprot/Q3TBW3|||http://purl.uniprot.org/uniprot/Q3UDT3|||http://purl.uniprot.org/uniprot/Q8BS14|||http://purl.uniprot.org/uniprot/Q8CI98 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in adult mouse spleen as well as in testis (PubMed:9235916). Isoform 1 is expressed in spleen and lung (at protein level). Isoform 1 is expressed predominantly in leukocytes.|||Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. Among other effects, IC87114 reduces allergic responses, prevents the recruitment of antigen-specific T cells into target tissue, and affects natural killer cell chemotaxis.|||Autophosphorylation on Ser-1038 results in the almost complete inactivation of the lipid kinase activity.|||Belongs to the PI3/PI4-kinase family.|||Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.|||Cytoplasm|||Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS and HRAS.|||Null mutants are viable and fertile but display defective adaptive and innate immune responses due to signaling defects in multiple cell types including B-, T- and mast and natural killer cells.|||Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:9235916). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. http://togogenome.org/gene/10090:Iqgap1 ^@ http://purl.uniprot.org/uniprot/Q9JKF1 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) In case of infection, interacts with S.typhimurium protein sseI (PubMed:19956712).|||Apical cell membrane|||Basolateral cell membrane|||Cell membrane|||Cytoplasm|||Expressed in the kidney (at protein level).|||Expressed widely in developing cortex.|||Interacts with CDC42; the interaction is demonstrated with IQGAP1 in GTP-bound and in nucleotide-free state (PubMed:16968698). Interacts with RAC1 (By similarity). Does not interact with RHOA (By similarity). Interacts with TSG101 (By similarity). Interacts with PAK6 (By similarity). Interacts with SASH1 (By similarity). Interacts with PJVK (PubMed:28089576). Interacts with SLC26A4 (PubMed:35601831). This interaction enhances the chloride-bicarbonate exchange activity of SLC26A4 (By similarity).|||Nucleus|||Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Binds to activated CDC42 but does not stimulate its GTPase activity (PubMed:16968698). It associates with calmodulin. Could serve as an assembly scaffold for the organization of a multimolecular complex that would interface incoming signals to the reorganization of the actin cytoskeleton at the plasma membrane. May promote neurite outgrowth. May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest.|||Regions C1 and C2 can either interact with nucleotide-free CDC42, or interact together. http://togogenome.org/gene/10090:Arid5b ^@ http://purl.uniprot.org/uniprot/Q8BM75 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ARID5B family.|||During smooth muscle cell differentiation in vitro. Upon adipogenesis.|||First detected in the intermediate plate mesoderm, and subsequently in the nephrogenic cords of the urogenital ridges. Expressed in the developing limb. Also expressed in the myotome of the somites from 9.5 dpc, the oro-nasopharyngeal ectoderm and underlying mesenchyme, otic vesicles, the gut and its derivatives, and transiently in the liver at 11.5 dpc.|||High rate of neonatal mortality. Embryonic growth or birth weight are not effected, while lipid accumulation is severely reduced in brown adipose neonates at 24 hours of age. Mice weigh significantly less than controls from postnatal day 5 onward. Adult mice are lean, with significant reductions in brown and white adipose tissues, and in the percentage of body fat. Mice are also resistant to weight gains and obesity when maintained on high-fat diets.|||Methylation at Lys-337 prevents DNA-binding. Demethylation by PHF2 promotes recruitment of the PHF2-ARID5B complex to promoters (By similarity).|||Nucleus|||The ARID domain mediates the interaction with DNA.|||Transcription coactivator that binds to the 5'-AATA[CT]-3' core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-337, leading to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver (By similarity). Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation.|||Widely expressed. Expressed in lung, heart, small intestine, kidney, muscle and brain. Also expressed in spleen, thymus, endocrine organs and in uterus and testis. http://togogenome.org/gene/10090:Or51e2 ^@ http://purl.uniprot.org/uniprot/Q8VBV9 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Conflicting results for the role of OR51E2 in the regulation of breathing and its role as a hypoxia sensor activated by lactate are reported (PubMed:26560302, PubMed:30258151). It was first described as a hypoxia sensor in the breathing circuit by sensing lactate produced when oxygen levels decline (PubMed:26560302). A recent study fails to confirm a role for OR52E2 in this pathway (PubMed:30258151). Conflicting results may reflect the use of different strain backgrounds (PubMed:30258152, PubMed:26560302, PubMed:30258151).|||Contradictory results have been reported for activation by beta-ionone in human and mouse. Beta-ionone does not activate OR51E2 in mouse. This difference may depend on the different methods used for these experiments, or may be due to species difference.|||Early endosome membrane|||In brain, expressed in medulla oblongata by cells close to the fourth ventricle, in the area postrema, the nucleus tractus solitarius (PubMed:11707321). Expressed in olfactory epithelium and vomeronasal organ (PubMed:11069588). Expressed in kidney by large renal vessels, renal afferent arterioles, and extrarenal vascular beds. In small resistance vessels the expression is restricted to cells of the juxtaglomerular afferent arteriole, which mediate renin secretion. Also detected in small blood vessels in a variety of tissues including heart, diaphragm, skeletal muscle, and skin. In the heart, esophagus, and stomach it is detected in axons of autonomic neurons and neurons of the enteric plexus (PubMed:23401498). Also detected in colon and liver (PubMed:23401498). Expressed in the glomus cells of the carotid body (PubMed:26560302).|||Knockout mice display reduced baseline blood pressure.|||Olfactory receptor. The activity of this receptor is probably mediated by G-proteins wich induce elevation of intracellular Ca(2+), cAMP and activation of phosphorylation of the protein kinases PKA and MAPK3/MAPK1. Activation of OR51E2 may affect melanocyte proliferation, differentiation, and melanogenesis and may increase proliferation and migration of primary retinal pigment epithelial (RPE) cells (By similarity). Activated by the short chain fatty acids (SCFA), acetate and propionate (PubMed:23401498). In response to SCFA, may positively regulate renin secretion and increase blood pressure (PubMed:23401498). May also be activated by steroid hormones and regulate cell proliferation (By similarity). Activated by L-lactate in glomus cells (PubMed:26560302, PubMed:30258151).|||Primarily detected between 11 dpc and 12 dpc. Expressed at 12 dpc in the dorsal region of the developing nasal cavity and in the mesenchyme located between the olfactory epithelium and the presumptive olfactory bulb. In the medulla oblongata, first detected at 17 dpc. In the area postrema and the nucleus tractus solitarius expression peaks at P20 and then decreases slightly. http://togogenome.org/gene/10090:Lysmd3 ^@ http://purl.uniprot.org/uniprot/Q99LE3 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Essential for Golgi structural integrity.|||Golgi apparatus http://togogenome.org/gene/10090:Gkn3 ^@ http://purl.uniprot.org/uniprot/Q9D0T7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the gastrokine family.|||Expressed in stomach. Present in mucus cells at the base of antral glands, and Brunner glands of the duodenum. Present at lower levels in the mucus neck cell region of the fundus (at protein level).|||Inhibits gastric epithelial cell proliferation.|||Secreted http://togogenome.org/gene/10090:Nxnl1 ^@ http://purl.uniprot.org/uniprot/Q8VC33 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleoredoxin family.|||Expressed in the retina (at protein level) (PubMed:15220920, PubMed:19843539). Expressed predominantly by photoreceptors in both the inner and outer nuclear layer (at protein level) (PubMed:15220920, PubMed:19843539). Not expressed in the testis, spleen, intestine, lung, cerebellum, or kidney (PubMed:15220920).|||Interacts with isoform 1 of BSG.|||Plays an important role in retinal cone photoreceptor survival (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and BSG, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May play a role in cone cell viability, slowing down cone degeneration, does not seem to play a role in degenerating rods (PubMed:15220920).|||photoreceptor outer segment http://togogenome.org/gene/10090:Adgrl2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JGM8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Prss57 ^@ http://purl.uniprot.org/uniprot/Q14B24 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ After cleavage of the signal peptide, the N-terminus is probably further processed by CTSC. Processing by CTSC is probably required for accumulation in cytoplasmic granules; in the absence of CTSC the protein does not accumulate.|||Belongs to the peptidase S1 family.|||Cytoplasmic granule lumen|||It is uncertain whether Met-1 or Met-7 is the initiator.|||N-glycosylated.|||Secreted|||Serine protease that cleaves preferentially after Arg residues. Can also cleave after citrulline (deimidated arginine) and methylarginine residues. http://togogenome.org/gene/10090:Polr1h ^@ http://purl.uniprot.org/uniprot/Q791N7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.|||Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors.|||nucleolus http://togogenome.org/gene/10090:Slc22a8 ^@ http://purl.uniprot.org/uniprot/O88909 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Expressed mainly in kidney (PubMed:12011098, PubMed:15100168, PubMed:10087192, PubMed:23389457). In kidney, detected in almost all parts of the nephron, including macula densa cells (PubMed:15944205). Expressed (at protein level) throughout the renal cortex (PubMed:17220594). Widely distributed in the brain with no large regional differences (PubMed:21325432). Expressed in the choroid plexus (CP, located in the ventricles of the brain) (PubMed:12011098). Expressed in developing bone (PubMed:10087192). Weakly expressed in brain and eye (PubMed:15100168).|||Expression inhibited by androgens such as testosterone.|||Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (By similarity). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:17220594). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:12011098, PubMed:15075193, PubMed:17220594, PubMed:21325432). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange. Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule. Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate. Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (By similarity). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (By similarity). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (By similarity). May contribute to the release of cortisol in the adrenals (By similarity). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (PubMed:12011098). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (PubMed:15100168, PubMed:17220594). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB) (By similarity). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (By similarity). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity).|||Mice appear healthy and are fertile. Exhibit a loss of taurocholate, estrone sulfate and para-aminohippurate transport in kidney and of fluorescein (FL) transport in choroid plexus. http://togogenome.org/gene/10090:Stk3 ^@ http://purl.uniprot.org/uniprot/Q9JI10 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with NEK2. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain). Interacts with LATS1; this interaction is inhibited in the presence of DLG5. Interacts with MARK3 in the presence of DLG5 (By similarity). Interacts with DLG5 (via PDZ domain 3) (PubMed:28087714).|||Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation (By similarity).|||Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age.|||Nucleus|||Phosphorylation at Thr-117 and Thr-390 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1.|||Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N).|||Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1. Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 (By similarity). http://togogenome.org/gene/10090:Prelp ^@ http://purl.uniprot.org/uniprot/Q9JK53 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.|||Binds the basement membrane heparan sulfate proteoglycan perlecan and triple helical collagens type I and type II.|||Expressed in cartilage throughout both fetal development and postnatal life. It is also expressed in the developing embryo prior to skeletogenesis. In adult, highest expression in lung, lower levels in cardiac and skeletal muscle.|||Glycosylated; contains heparan sulfate.|||May anchor basement membranes to the underlying connective tissue.|||The basic N-terminal Arg/Pro-rich binds heparin and heparan sulfate. Binds collagens type I and type II through its leucine-rich repeat domain.|||extracellular matrix http://togogenome.org/gene/10090:Rp1l1 ^@ http://purl.uniprot.org/uniprot/Q8CGM2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in retina at birth but not at prenatal stages.|||Interacts with RP1; has a synergistic effect with RP1 in photoreceptor differentiation.|||Mice display scattered outer segment disorganization, reduced electroretinogram amplitudes, and progressive photoreceptor degeneration. In single rods defective cells photosensitivity is reduced. Rp1 and Rp1l1 double heterozygotes exhibits abnormal outer segment morphology and reduced single rod photosensitivity and dark currents, while individual heterozygotes are normal.|||Required for the differentiation of photoreceptor cells. Plays a role in the organization of outer segment of rod and cone photoreceptors.|||Retinal-specific; expressed in photoreceptor.|||cilium axoneme|||photoreceptor outer segment http://togogenome.org/gene/10090:Abca13 ^@ http://purl.uniprot.org/uniprot/Q5SSE9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily.|||Cytoplasmic vesicle membrane|||Homozygous knockout mice for Abca13 are born normally and seem to have normal appearance and life span but show sensorimotor gating deficits.|||May mediate the cholesterol and gangliosides transport from the plasma membrane to intracellular vesicles in an ATP hydrolysis dependent manner, thus playing a role in their internalization by endocytic retrograde transport and may also participate in the endocytosis of synaptic vesicle in cortical neurons.|||Ubiquitously expressed. May be primarily expressed in kidney. http://togogenome.org/gene/10090:Mttp ^@ http://purl.uniprot.org/uniprot/O08601 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:15897609, PubMed:16478722, PubMed:18502767, PubMed:33168624). Required for the assembly and secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:17635917, PubMed:10713055, PubMed:9502759, PubMed:18502767, PubMed:33168624). May be involved in regulating cholesteryl ester biosynthesis in cells that produce lipoproteins (PubMed:18502767).|||Cleaved by signal peptidase between residues Gln-33 and Asn-34.|||Critical for the development of natural killer T (NKT) cells (PubMed:17312007). Required for the assembly and secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:17635917).|||Endoplasmic reticulum|||Expression in the yolk sac tissues followed by expression in the primordial liver cell nests as early as day 9 post-coitum (9.5 dpc). Intestinal expression is detected around 12.5 dpc and attains full adult expression patterns by 14.5 dpc.|||Golgi apparatus|||Heterodimer; heterodimerizes with the protein disulfide isomerase (P4HB/PDI) (PubMed:17635917).|||Heterodimer; heterodimerizes with the protein disulfide isomerase (P4HB/PDI) (PubMed:17635917). Interacts with APOB (By similarity).|||Interacts with PRAP1.|||Lowers plasma and tissue triglyceride levels, and increases cellular free cholesterol.|||Mainly expressed in the intestine and the liver, and at lower levels in white and brown fat cells (PubMed:17635917, PubMed:8660984). Expressed in heart (PubMed:9502759).|||Ubiquitous, and is the major isoform in hematopoietic cells and adipocytes.|||Up-regulated by FOXO1. Expressed in a circadian manner in the liver. http://togogenome.org/gene/10090:Tlr4 ^@ http://purl.uniprot.org/uniprot/L0CL36|||http://purl.uniprot.org/uniprot/Q9QUK6 ^@ Caution|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Required for the virulence of fungus C.neoformans var. grubii serotype A (strain KN99) CPL1 (PubMed:35896747). Independently of Ly96/Md2, activated by CPL1 which results in a type 2 inflammation response characterized by Arg1/arginase-1 induction in interstitial macrophages (PubMed:35896747).|||Belongs to the Toll-like receptor family.|||Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (PubMed:24380872). Binding to bacterial LPS leads to homodimerization (PubMed:20133493, PubMed:24380872, PubMed:22532668). Interacts with LY96 via the extracellular domain (PubMed:17803912, PubMed:22532668). Interacts with MYD88 (via the TIR domain). Interacts with TICAM2 and TIRAP (PubMed:24380872). Interacts with NOX4 (By similarity). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800). Interacts with MAP3K21; this interaction leads to negative regulation of TLR4 signaling (By similarity). Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR6. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation (By similarity). Interacts with TICAM1 in response to LPS in a WDFY1-dependent manner (PubMed:25736436). Interacts with WDFY1 in response to LPS (PubMed:25736436). Interacts with SMPDL3B (PubMed:26095358). Interacts with CEACAM1; upon lipopolysaccharide stimulation, forms a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (PubMed:22496641). Interacts with RFTN1; the interaction occurs in response to lipopolysaccharide stimulation (By similarity). Interacts with SCIMP; the interaction occurs in response to lipopolysaccharide stimulation and is enhanced by phosphorylation of SCIMP by LYN (PubMed:28098138). This interaction facilitates the phosphorylation of TLR4 by LYN which elicits a selective cytokine response in macrophages (PubMed:28098138). Interacts with TRAF3IP3 (By similarity). Interacts with TREM1; this interaction enhances TLR4-mediated inflammatory response (By similarity).|||Cell membrane|||Early endosome|||Expressed in macrophages (at protein level) (PubMed:28098138, PubMed:35896747). Highly expressed in heart, spleen, lung and muscle. Lower levels are found in liver and kidney (PubMed:23812099).|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||Interstrain analysis reveals that TLR4 is a polymorphic protein and that the extracellular domain is far more variable than the cytoplasmic domain, which is variable at the C-terminal.|||Membrane|||Mice infected with C.neoformans var. grubii serotype A (strain KN99) display reduced Arg1/arginase-1 expression in interstitial macrophages as well as reduced pulmonary fungal burden and eosinophilia (PubMed:35896747). Animals with a double knockout of Apoe and Tlr4, fed a Western diet for 12 weeks, have less aortic plaque formation than single Apoe knockout mice. They also show lower serum concentrations of Il1a, Ilb and Il18 (PubMed:23812099).|||Phosphorylated on tyrosine residues by LYN after binding lipopolysaccharide.|||The TIR domain mediates interaction with NOX4.|||The protein is encoded by the Lps locus, an important susceptibility locus, influencing the propensity to develop a disseminated Gram-negative infection.|||Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways (PubMed:9851930, PubMed:9989976, PubMed:20133493). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:9851930, PubMed:9989976, PubMed:20133493). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:24380872). Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production. In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade. In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86. Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway. In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner (By similarity).|||ruffle http://togogenome.org/gene/10090:Clrn3 ^@ http://purl.uniprot.org/uniprot/Q8BHH8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the clarin family.|||Membrane http://togogenome.org/gene/10090:Anp32b ^@ http://purl.uniprot.org/uniprot/Q9EST5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ANP32 family.|||Deficient mice display an highly penetrant perinatal lethality in a mixed genetic background and a fully penetrant lethality in a pure C57BL/6 background (PubMed:21636789). Mutants also show enhanced clinical symptoms correlated with depletion of naive effector T-cells, exhaustion of lymphocytes and enhanced prevalence of follicular T-helper cells (PubMed:30890743). In addition, mice show significantly reduced H3N2 or H5N1 influenza viral loads, inflammatory cytokine response and reduced pathogenicity compared to WT (PubMed:32231671).|||Directly cleaved by caspase-3/CASP3.|||Histone binding is mediated by the concave surface of the LRR region.|||Interacts with histones H3 and H4. Interacts with KLF5; this interaction induces promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B.|||Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription (PubMed:21636789). Regulates the proliferation of neuronal stem cells, differentiation of leukemic cells and progression from G1 to S phase of the cell cycle. As negative regulator of caspase-3-dependent apoptosis, may act as an antagonist of ANP32A in regulating tissue homeostasis (By similarity). Exhibits histone chaperone properties, able to recruit histones to certain promoters, thus regulating the transcription of specific genes (By similarity). Also plays an essential role in the nucleocytoplasmic transport of specific mRNAs via the uncommon nuclear mRNA export receptor XPO1/CRM1 (By similarity). Participates in the regulation of adequate adaptive immune responses by acting on mRNA expression and cell proliferation (PubMed:30890743).|||Nucleus|||Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group. http://togogenome.org/gene/10090:Grin1 ^@ http://purl.uniprot.org/uniprot/A2AI16|||http://purl.uniprot.org/uniprot/P35438 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily.|||Cell membrane|||Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:1532151, PubMed:8060614, PubMed:12008020). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:12008020).|||Detected in brain (at protein level). Detected in brain.|||Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B) (PubMed:12008020, PubMed:14602821). Found in a complex with GRIN2A or GRIN2B and GRIN3B (PubMed:12008020, PubMed:14602821). Found in a complex with GRIN2A or GRIN2B, GRIN3A and PPP2CB (By similarity). Interacts with DLG4 and MPDZ (By similarity). Interacts with LRFN1 and LRFN2 (By similarity). Interacts with MYZAP (PubMed:18849881). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:23524343). Found in a complex with DLG4 and PRR7 (By similarity). Found in a complex with GRIN2B and PRR7 (By similarity). Interacts with PRR7; the interaction is reduced following NMDA receptor activity (By similarity).|||Membrane|||Mutant mice are born at the expected Mendelian rate, appear grossly normal and have apparently normal brain structure, but the pups do not feed and all die during the first day after birth. Cerebellum granule cells and hippocampus pyramidal neurons from mutants lack NMDA-induced Ca(2+)influx and membrane currents, contrary to wild-type.|||NMDA is probably regulated by C-terminal phosphorylation of an isoform of NR1 by PKC. Dephosphorylated on Ser-897 probably by protein phosphatase 2A (PPP2CB). Its phosphorylated state is influenced by the formation of the NMDAR-PPP2CB complex and the NMDAR channel activity (By similarity).|||Postsynaptic cell membrane|||Postsynaptic density|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. http://togogenome.org/gene/10090:Fstl1 ^@ http://purl.uniprot.org/uniprot/Q62356 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Deletion mice die at birth from respiratory distress and show multiple defects in lung development. In addition, skeletal development is strongly impaired.|||During central nervous system development, strongly expressed in the telencephalon, diencephalon, brainstem, limbic system and spinal cord (PubMed:19595790). Widely expressed in all organs (PubMed:21826198).|||Homodimer (PubMed:31351024). Interacts with SCN10A (By similarity). Interacts with DIP2A; DIP2A may act as a cell surface receptor for FSTL1 (PubMed:20054002). Interacts with BMP4 (By similarity). Interacts with CD14; this interaction promotes TL4-mediated signaling cascade (By similarity).|||Secreted|||Secreted glycoprotein that is involved in various physiological processes, such as angiogenesis, regulation of the immune response, cell proliferation and differentiation (By similarity). Plays a role in the development of the central nervous system, skeletal system, lungs, and ureter (PubMed:21826198, PubMed:19595790). Promotes endothelial cell survival, migration and differentiation into network structures in an AKT-dependent manner. Also promotes survival of cardiac myocytes (PubMed:20054002). Initiates various signaling cascades by activating different receptors on the cell surface such as DIP2A, TLR4 or BMP receptors (By similarity). http://togogenome.org/gene/10090:Clvs1 ^@ http://purl.uniprot.org/uniprot/Q9D4C9 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Binding to PtdIns(3,5)P2 is not required for localization.|||Early endosome membrane|||Forms a complex with clathrin heavy chain and gamma-adaptin.|||Required for normal morphology of late endosomes and/or lysosomes in neurons. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (By similarity).|||The CRAL-TRIO domain is required for targeting to the membrane and for binding PtdIns(3,5)P2.|||clathrin-coated vesicle|||trans-Golgi network membrane http://togogenome.org/gene/10090:Bpifa1 ^@ http://purl.uniprot.org/uniprot/P97361 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BPI/LBP/Plunc superfamily. Plunc family.|||Detected in airway epithelia (trachea and lung) and in bronchoalveolar fluid (at protein level). Upper airways, nasopharyngeal epithelium and thymus. Highest expression in the trachea and progressive decrease from proximal (bronchial) to distal (bronchiolar) airways. No expression is detected in the terminal bronchioles, respiratory bronchioles or lung alveoli.|||First detected at 14.5 dpc in the nasopharyngeal epithelium and persists there into adulthood. In the thymus, weak expression is detected at 16.5 dpc and appears to be restricted to epithelial cells lining the medullary venules. This pattern of thymic expression persists until birth and into early postnatal life but is greatly decreased in the adult thymus. No expression is detected in the lung until 2 days after birth, after which expression is detected in cells lining the trachea.|||Lipid-binding protein which shows high specificity for the surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) (By similarity). Plays a role in the innate immune responses of the upper airways (PubMed:23499554). Reduces the surface tension in secretions from airway epithelia and inhibits the formation of biofilm by pathogenic Gram-negative bacteria, such as P.aeruginosa and K.pneumoniae (PubMed:23499554). Negatively regulates proteolytic cleavage of SCNN1G, an event that is required for activation of the epithelial sodium channel (ENaC), and thereby contributes to airway surface liquid homeostasis and proper clearance of mucus (By similarity). Plays a role in the airway inflammatory response after exposure to irritants (By similarity). May attract macrophages and neutrophils (By similarity).|||Monomer. Interacts (via N-terminus) with SCNN1B, a subunit of the heterotrimeric epithelial sodium channel (ENaC); this inhibits proteolytic activation of ENaC (By similarity).|||Reported to bind to bacterial lipopolysaccharide (LPS) in vitro. However, the in vivo significance of this is uncertain since other studies indicate little or no specificity for LPS.|||Secreted http://togogenome.org/gene/10090:H2al1c ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:Cherp ^@ http://purl.uniprot.org/uniprot/Q8CGZ0 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Endoplasmic reticulum|||Involved in calcium homeostasis, growth and proliferation.|||perinuclear region http://togogenome.org/gene/10090:Baz2a ^@ http://purl.uniprot.org/uniprot/E9Q374|||http://purl.uniprot.org/uniprot/F8VPM0 ^@ Similarity ^@ Belongs to the WAL family. http://togogenome.org/gene/10090:Mri1 ^@ http://purl.uniprot.org/uniprot/Q9CQT1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the eIF-2B alpha/beta/delta subunits family. MtnA subfamily.|||Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Ipcef1 ^@ http://purl.uniprot.org/uniprot/Q5DU31 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Enhances the promotion of guanine-nucleotide exchange by PSCD2 on ARF6 in a concentration-dependent manner.|||Interacts with guanine-nucleotide exchange factors PSCD1, PSCD2, PSCD3 and PSCD4. http://togogenome.org/gene/10090:Ccdc51 ^@ http://purl.uniprot.org/uniprot/Q3URS9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Inhibited by ATP via mitoK(ATP) channel.|||Knockout mice exhibit no visible phenotype (PubMed:31435016). Mutant mice are slightly more sensitive to the ischaemia-reperfusion protocol (PubMed:31435016).|||Mitochondrial potassium channel located in the mitochondrial inner membrane (PubMed:31435016). Together with ABCB8/MITOSUR, forms a protein complex localized in the mitochondria that mediates ATP-dependent potassium currents across the inner membrane (that is, mitoK(ATP) channel) (PubMed:31435016). May contribute to the homeostatic control of cellular metabolism under stress conditions by regulating the mitochondrial matrix volume (PubMed:31435016).|||Mitochondrion inner membrane|||The mitochondrial potassium channel (mitoK(ATP)) is composed of 4 subunits of CCDC51/MITOK and 4 subunits of ABCB8/MITOSUR. http://togogenome.org/gene/10090:Ttll1 ^@ http://purl.uniprot.org/uniprot/Q91V51 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin polyglutamylase family.|||Catalytic subunit of a polyglutamylase complex which modifies tubulin, generating side chains of glutamate on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin (PubMed:15890843). Probably involved in the side-chain elongation step of the polyglutamylation reaction rather than the initiation step (Probable). Modifies both alpha- and beta-tubulins with a preference for the alpha-tail (PubMed:15890843, PubMed:22170066). Unlike most polyglutamylases of the tubulin--tyrosine ligase family, only displays a catalytic activity when in complex with other proteins as it is most likely lacking domains important for autonomous activity (PubMed:15890843). Part of the neuronal tubulin polyglutamylase complex (PubMed:15890843). Mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility (PubMed:20498047, PubMed:20442420, PubMed:23897886). Involved in respiratory motile cilia function through the regulation of beating asymmetry (PubMed:20498047, PubMed:20442420). Essential for sperm flagella biogenesis, motility and male fertility (PubMed:20442420). Also mediates glutamylation of non-tubulin proteins (PubMed:29593216). Involved in KLF4 glutamylation which impedes its ubiquitination, thereby leading to somatic cell reprogramming, pluripotency maintenance and embryogenesis (PubMed:29593216).|||Gln-144 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in brain, heart and kidney (PubMed:17499049, PubMed:20442420). Expressed in liver, lung, muscle, spleen, testis and trachea (PubMed:17499049, PubMed:20442420). In the brain, expressed in ependymal cilia, cortex, corpus callosum and striatum (PubMed:23897886). Expressed in blastomere (PubMed:29593216).|||Knockout mice exhibit a loss of axonemal curvature and beating asymmetry in tracheal epithelial cilia, resulting in a reduction of cilia-generated fluid flow in trachea (PubMed:20498047). Knockout mice exhibit accumulations of exudates in the nasal passages and sinuses, rhinosinusitis and otitis media, and also emitted frequent coughing- or sneezing-like noises (PubMed:20498047, PubMed:20442420). Knockout male show abnormal sperm morphology and function characterized by shortened or absent flagella and immotility, and male infertility (PubMed:20498047, PubMed:20442420). Partial loss of tubulin glutamylation, probably due to redundancy with other polyglutamylases (PubMed:20498047).|||Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1. Interacts with PCM1, CSTPP1 and LRRC49 (By similarity).|||cilium axoneme|||cilium basal body|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Mvb12b ^@ http://purl.uniprot.org/uniprot/Q6KAU4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MVB12 family.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS28. Interacts with VPS37B; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37C; the association appears to be mediated by the TSG101-VPS37 binary subcomplex (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (By similarity).|||Endosome|||Late endosome membrane http://togogenome.org/gene/10090:Tspan11 ^@ http://purl.uniprot.org/uniprot/Q9D1D1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||Membrane http://togogenome.org/gene/10090:Rpl30 ^@ http://purl.uniprot.org/uniprot/P62889|||http://purl.uniprot.org/uniprot/Q497D7|||http://purl.uniprot.org/uniprot/Q58DZ3|||http://purl.uniprot.org/uniprot/Q5PR15 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL30 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Vmn1r203 ^@ http://purl.uniprot.org/uniprot/Q8R273 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Akirin2 ^@ http://purl.uniprot.org/uniprot/B1AXD8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Akiraka ni suru' means 'making things clear' in Japanese. The name is given based on the presence of the clear nuclear localization signal.|||Belongs to the akirin family.|||Cytoplasm|||Expressed throughout cortical development: present throughout the cortical wall at all of these ages, with strong expression in the early ventricular zone and the embryonic preplate/cortical plate (PubMed:27871306). Expressed in the developing limb: expressed in the forelimb bud and somites at 10.5 dpc, as well as in the apical ectodermal ridge (AER) (PubMed:30116001). Ubiquitously expressed throughout the embryonic forelimb at 10.5 dpc: expressed in the dermomyotome and sclerotome divisions of the somite (at protein level) (PubMed:30801883).|||Homodimer (By similarity). Interacts with IPO9; the interaction is direct (By similarity). Associates with 20S and 26S proteasomes (By similarity). Interacts with SMARCD1; promoting SWI/SNF complex recruitment (PubMed:25107474). Interacts with NFKBIZ (PubMed:25107474). Interacts with YWHAB (By similarity).|||Membrane|||Mice are embryonic lethal (PubMed:18066067). Null mutant embryos could not be detected even on embryonic day 9.5 (PubMed:18066067). Conditional deletion in macrophages impairs proinflammatory cytokine production in response to Listeria infection and clearance of infecting bacteria (PubMed:25107474). Conditional deletion in B-cells causes a decrease in the splenic B-cell numbers, leading to severe proliferation and activation defects in B-cells (PubMed:26041538). The B-cell viability is also impaired, leading to decreased immune responses to T-dependent and T-independent antigens (PubMed:26041538). Conditional deletion in the cortex leads to severe microcephaly: mice do not survive past birth and exhibit extreme microcephaly, with little dorsal telencephalic tissue and no recognizable cortex (PubMed:27871306). Defects in the cortex are caused to massive cell death of early cortical progenitors (PubMed:27871306). Conditional deletion in somitic muscle precursor cells results in neonatal lethality: mutant embryos show a complete lack of forelimb, intercostal and diaphragm muscles due to extensive apoptosis and loss of myoblasts (PubMed:30801883). Embryos lacking Akirin2 in somitic muscle precursor cells also display severe skeletal defects, including craniofacial abnormalities, disrupted ossification and rib fusions (PubMed:30801883). Conditional deletion in limb bud epithelium leads to soft-tissue syndactyly, characterized by a loss of interdigital cell death and an increase in cell proliferation, resulting in retention of the interdigital web (PubMed:30116001).|||Molecular adapter that acts as a bridge between a variety of multiprotein complexes, and which is involved in embryonic development, immunity, myogenesis and brain development (PubMed:25107474, PubMed:26041538, PubMed:27871306, PubMed:30116001, PubMed:30801883). Plays a key role in nuclear protein degradation by promoting import of proteasomes into the nucleus: directly binds to fully assembled 20S proteasomes at one end and to nuclear import receptor IPO9 at the other end, bridging them together and mediating the import of pre-assembled proteasome complexes through the nuclear pore (By similarity). Involved in innate immunity by regulating the production of interleukin-6 (IL6) downstream of Toll-like receptor (TLR): acts by bridging the NF-kappa-B inhibitor NFKBIZ and the SWI/SNF complex, leading to promote induction of IL6 (PubMed:18066067, PubMed:25107474). Also involved in adaptive immunity by promoting B-cell activation (PubMed:26041538). Involved in brain development: required for the survival and proliferation of cerebral cortical progenitor cells (PubMed:27871306). Involved in myogenesis: required for skeletal muscle formation and skeletal development, possibly by regulating expression of muscle differentiation factors (PubMed:30801883). Also plays a role in facilitating interdigital tissue regression during limb development (PubMed:30116001).|||Nucleus http://togogenome.org/gene/10090:Ryr3 ^@ http://purl.uniprot.org/uniprot/A0A140LJK7|||http://purl.uniprot.org/uniprot/A2AGL3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR3 subfamily.|||Channel activity is modulated by the alkaloid ryanodine that binds to the open calcium-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by elevated cytoplasmic calcium levels in the micromolar range, by caffeine and adenine nucleotides, such as AMP and ATP. Inhibited by Mg(2+) and ruthenium red.|||Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction. May regulate Ca(2+) release by other calcium channels. Calcium channel that mediates Ca(2+)-induced Ca(2+) release from the endoplasmic reticulum in non-muscle cells. Plays a role in cellular calcium signaling. Contributes to cellular calcium ion homeostasis. Isoform 2 lacks a predicted transmembrane segment and does not form functional calcium channels by itself; however, it can form tetramers with isoforms that contain the full complement of transmembrane segments and modulate their activity.|||Detected in hippocampus, cerebellum, striatum, frontal brain cortex and parietal brain cortex. Detected in skeletal muscle, diaphragm muscle and myometrium (at protein level). Detected in egg cells. Detected in heart, diaphragm, stomach, spleen, ovary, testis germ cells, brain and cerebellum. Detected in cerebral artery smooth muscle cells.|||Homotetramer. Isoform 2 can form tetramers with isoform 1. Heterotetramer with RYR2. Interacts with FKBP1A. Interacts with CALM. Interacts with SELENON (By similarity).|||Lacks a predicted transmembrane segment and is not expected to form functional calcium channels.|||Membrane|||No apparent phenotype. Mice are born at the expected Mendelian rate and are fertile. They appear normal, except for increased locomotor activity and decreased social contact duration in social interaction tests.|||Sarcoplasmic reticulum membrane|||The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm. http://togogenome.org/gene/10090:Or6c66 ^@ http://purl.uniprot.org/uniprot/Q7TRH8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il3 ^@ http://purl.uniprot.org/uniprot/P01586|||http://purl.uniprot.org/uniprot/Q5SX77 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated T-cells, mast cells, natural killer cells.|||Belongs to the IL-3 family.|||Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated. In addition, plays an important role in neural cell proliferation and survival. Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation. Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB (By similarity). Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program (PubMed:8378315, PubMed:10376805, PubMed:31990690). Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK (By similarity).|||Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated. In addition, plays an important role in neural cell proliferation and survival. Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation. Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB. Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program. Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK.|||IL-3-deficient animals show no abnormalities. Analysis of steady-state hematopoiesis demonstrates normal numbers of peripheral blood cells, bone marrow and splenic hematopoietic progenitors. However, they show impaired contact hypersensitivity reactions.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Pet117 ^@ http://purl.uniprot.org/uniprot/P0DJF2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PET117 family.|||Mitochondrion http://togogenome.org/gene/10090:Pyroxd2 ^@ http://purl.uniprot.org/uniprot/Q3U4I7 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the carotenoid/retinoid oxidoreductase family.|||Interacts with COX5B; this interaction may contribute to localize PYROXD2 to the inner face of the inner mitochondrial membrane.|||Intron retention between positions 50 and 165.|||Mitochondrion matrix|||Probable oxidoreductase that may play a role as regulator of mitochondrial function. http://togogenome.org/gene/10090:Fthl17b ^@ http://purl.uniprot.org/uniprot/A2AHC5 ^@ Function|||Similarity ^@ Belongs to the ferritin family.|||Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. http://togogenome.org/gene/10090:Gmpr ^@ http://purl.uniprot.org/uniprot/Q9DCZ1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.|||Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides.|||Homotetramer. http://togogenome.org/gene/10090:Kctd10 ^@ http://purl.uniprot.org/uniprot/F8WGQ9|||http://purl.uniprot.org/uniprot/Q922M3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BACURD family.|||Homotetramer; forms a two-fold symmetric tetramer in solution. Interacts with CUL3; interaction is direct and forms a 5:5 heterodecamer (By similarity). Component of the BCR(BACURD3) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD10/BACURD3 and RBX1 (By similarity). Interacts with DNA polymerase delta subunit 2/POLD2 (By similarity). Interacts with PCNA (By similarity). Associated with the tectonic-like complex (also named B9 complex); however as Kctd10 has not been identified in all tectonic-like complexes purifications it is unclear whether it is really part of the complex (PubMed:22179047).|||Nucleus|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. The BCR(BACURD3) E3 ubiquitin ligase complex mediates the ubiquitination of target proteins, leading to their degradation by the proteasome (By similarity). http://togogenome.org/gene/10090:Defa36 ^@ http://purl.uniprot.org/uniprot/K9J724 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Defb2 ^@ http://purl.uniprot.org/uniprot/P82020 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has bactericidal activity.|||In tracheal epithelium, by lipopolysaccharide or inflammation.|||Kidney, uterus and to a lesser extent in heart.|||Secreted http://togogenome.org/gene/10090:Tas2r131 ^@ http://purl.uniprot.org/uniprot/Q7M708 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane http://togogenome.org/gene/10090:Ntrk2 ^@ http://purl.uniprot.org/uniprot/P15209 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Early endosome membrane|||Endosome membrane|||Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor (By similarity). Interacts with SORCS2; this interaction is important for normal targeting to post-synaptic densities in response to high-frequency stimulation (PubMed:27457814). Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway (By similarity). Interacts with APPL1 (PubMed:21849472). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3 (By similarity). Interacts with SORL1; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (PubMed:23977241).|||Expressed in the brain, in neurons (at protein level) (PubMed:23977241). Detected in hippocampus (at protein level) (PubMed:27457814). Widely expressed in the central and peripheral nervous system. The different forms are differentially expressed in various cell types. Isoform GP95-TRKB is specifically expressed in glial cells.|||Expression oscillates in a circadian manner in the liver.|||Mice lacking isoform GP145-TRKB, the catalytic isoform, do not display feeding activity and die at P1. This is associated neuronal deficiencies in the central and the peripheral nervous systems.|||Non-catalytic isoform.|||Phosphorylated. Undergoes ligand-mediated autophosphorylation that is required for interaction with SHC1 and PLCG1 and other downstream effectors (PubMed:27457814). Some isoforms are not phosphorylated (By similarity).|||Postsynaptic density|||Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. Isoform GP95-TRKB may also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.|||The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms (By similarity). The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades.|||Ubiquitinated. Undergoes polyubiquitination upon activation; regulated by NGFR. Ubiquitination regulates the internalization of the receptor.|||axon|||dendrite|||perinuclear region http://togogenome.org/gene/10090:Faxc ^@ http://purl.uniprot.org/uniprot/Q3UMF9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAX family.|||May play a role in axonal development.|||Membrane http://togogenome.org/gene/10090:Tyw3 ^@ http://purl.uniprot.org/uniprot/E9PYE2|||http://purl.uniprot.org/uniprot/Q8BSA9 ^@ Function|||Similarity ^@ Belongs to the TYW3 family.|||Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA (By similarity).|||Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. http://togogenome.org/gene/10090:Vmn1r59 ^@ http://purl.uniprot.org/uniprot/Q8R2B9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bckdk ^@ http://purl.uniprot.org/uniprot/O55028|||http://purl.uniprot.org/uniprot/Q3UCB5 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the PDK/BCKDK protein kinase family.|||Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex.|||Expression in female liver is influenced by circadian rhythm.|||Mitochondrion|||Mitochondrion matrix|||Monomer.|||Mutant animals are born at the expected Mendelian ratio, but they exhibit a decreased fertility. They are healthy at birth. At 3 weeks of age, they start showing growth retardation. At 12 weeks, they are 15% smaller than their wild-type littermates. Adults develop neurological abnormalities, such as tremors, epileptic seizures and hindlimb clasping. These neurological deficits can be completely abolished when mice are fed with a diet enriched in branched amino acids.|||Ubiquitous. http://togogenome.org/gene/10090:Rbbp8 ^@ http://purl.uniprot.org/uniprot/Q80YR6 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COM1/SAE2/CtIP family.|||Binds one Zn(2+) atom per dimer. Zn(2+)-binding is not required for homotetramerization.|||Chromosome|||Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway (By similarity). HR is restricted to S and G2 phases of the cell cycle and preferentially repairs DSBs resulting from replication fork collapse (By similarity). Key determinant of DSB repair pathway choice, as it commits cells to HR by preventing classical non-homologous end-joining (NHEJ) (By similarity). Functions downstream of the MRN complex and ATM, promotes ATR activation and its recruitment to DSBs in the S/G2 phase facilitating the generation of ssDNA (By similarity). Component of the BRCA1-RBBP8 complex that regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage (By similarity). During immunoglobulin heavy chain class-switch recombination, promotes microhomology-mediated alternative end joining (A-NHEJ) and plays an essential role in chromosomal translocations (PubMed:21131978, PubMed:21131982). Binds preferentially to DNA Y-junctions and to DNA substrates with blocked ends and promotes intermolecular DNA bridging (By similarity).|||Homotetramer; formed by antiparallel association of helical extensions protruding from the N-termini of two parallel coiled-coil dimers (By similarity). Forms a dumbbell-shaped particle in which polar globular domains are held about 30 nm apart by a central rod (By similarity). Homotetramerization is required for DNA-end resection and repair (By similarity). Interacts (via the PXDLS motif) with CTBP1; the interaction is disrupted via binding of the adenovirus E1A to CTBP1. Component of the BRCA1-RBBP8 complex. Interacts (the Ser-326 phosphorylated form) with BRCA1 (via the C-terminal BRCT domains): the interaction occurs in the G2 phase, ubiquitinates RBBP8 and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Interacts with RB1. Interacts with the MRN complex. Interacts directly with MRE11; the interaction is required for efficient homologous recombination (HR) and regulation of the MRN complex. Interacts directly with RAD50. Interacts directly with NBN. Interacts with LMO4 (via the LIM zinc-binding 1 domain) (PubMed:23353824). Interacts with SIAH1. Interacts with RNF138. Interacts with EXD2. Interacts with CUL3 and KLHL15; this interaction leads to RBBP8 proteasomal degradation. Directly interacts with PIN1; this interaction depends upon RBBP8 phosphorylation, predominantly at Thr-315. Interacts with FZR1; this interaction leads to APC/C-mediated RBBP8 proteasomal degradation. Interacts with AUNIP; leading to recruit RBBP8 to sites of DNA damage. Interacts with SAMHD1 (By similarity). Interacts with HDGFL2 (By similarity).|||Hyperphosphorylation upon ionizing radiation results in dissociation from BRCA1. Phosphorylation at Thr-843 by CDK1 is essential for the recruitment to DNA and the DNA repair function. Phosphorylated at Ser-326 as cells enter G2 phase. This phosphorylation is required for binding BRCA1 and for the G2/M DNA damage transition checkpoint control (By similarity). Phosphorylation at Thr-315 is required for PIN1-binding, while phosphorylation at Ser-276 serves as a PIN1 isomerization site. Phosphorylation at Thr-315 is cell-cycle dependent. It steadily increases during S phase, peaks at late S/G2 phase, and drops at G1 (By similarity). Phosphorylation is not required for tetramerization (By similarity). Binds to DNA more strongly when dephosphorylated (By similarity).|||Nucleus|||The PXDLS motif binds to a cleft in CtBP proteins.|||The damage-recruitment motif is required for DNA binding and translocation to sites of DNA damage.|||Ubiquitinated. Ubiquitination at multiple sites by BRCA1 (via its N-terminal RING domain) does not lead to its proteasomal degradation but instead the ubiquitinated RBBP8 binds to chromatin following DNA damage and may play a role in G2/M checkpoint control. Ubiquitinated by RNF138 at its N-terminus. Ubiquitinated through 'Lys-48' by the E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation. Ubiquitinated by the E3 FZR1/APC/C complex; this modification leads to proteasomal degradation.|||Upon DNA damage, was shown to interact with SIRT6 resulting in its deacetylation. However, this study was later retracted. http://togogenome.org/gene/10090:Map7 ^@ http://purl.uniprot.org/uniprot/D3YWN7|||http://purl.uniprot.org/uniprot/E9QMU3|||http://purl.uniprot.org/uniprot/O88735 ^@ Developmental Stage|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the MAP7 family.|||Contaminating sequence. Potential poly-A sequence.|||Expressed in several epithelia from 9.5 dpc onwards, with expression levels increasing during development. From 14.5 dpc onwards, found in some neuronal cells as well.|||Highly expressed in the epithelial cells of the kidney tubules and in the absorptive cells of the intestine, and widely distributed in the testis. Expression correlates with the differentiation of certain epithelial cell types: in the adult intestine, more abundantly expressed in the differentiating than in the proliferative cell compartment. The expression clearly correlates with the degree of cellular apicobasal polarity. Expressed in lung, kidney, brain and fat. Colocalized with TRPV4 in ependymal cells, in the choroid plexus, in bronchial and renal cortical tubular cells. Widely expressed in excitable neuronal cells, vascular cells as well as in epithelial cells. In seminiferous epithelium, associated with the microtubule of the spermatid manchette.|||Interacts with TRPV4.|||Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments.|||The association with microtubules is regulated by phosphorylation during the cell cycle. During interphase only phosphorylated on serine. Phosphorylated on threonine in mitosis (By similarity).|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Raet1d ^@ http://purl.uniprot.org/uniprot/Q9JI58 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Acts as a ligand for KLRK1.|||Belongs to the NKG2D ligand family.|||By retinoic acid.|||Cell membrane|||Expressed predominantly during early embryogenesis. Detected at high levels in 7, 11 and 14-day-old embryos but not in 18-day-old embryos. Very low levels detected in adults.|||Glycosylated. http://togogenome.org/gene/10090:Or10c1 ^@ http://purl.uniprot.org/uniprot/Q8VFE2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Epb41l2 ^@ http://purl.uniprot.org/uniprot/O70318 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with FCGR1A. Interacts with TRPC4 (By similarity). Interacts (via CTD domain) with FKBP2 (PubMed:9531554). Interacts with NUMA1; this interaction is negatively regulated by CDK1 during metaphase and promotes anaphase-specific localization of NUMA1 in symmetrically dividing cells (By similarity).|||Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase.|||Widely expressed.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Chd3 ^@ http://purl.uniprot.org/uniprot/B1AR17|||http://purl.uniprot.org/uniprot/E9Q614 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SNF2/RAD54 helicase family.|||Nucleus http://togogenome.org/gene/10090:Adnp2 ^@ http://purl.uniprot.org/uniprot/Q8CHC8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed at 7.5 dpc, increasing by 9.5 dpc, concomitant with cranial neural tube closure, and at 11.5 dpc (PubMed:18179478). Expression levels were relatively stable between 12.5 dpc and birth, continuing into adulthood (PubMed:18179478).|||Expressed widely, with the highest level in the brain.|||May be involved in transcriptional regulation (PubMed:23071114). May play a role in neuronal function; perhaps involved in protection of brain tissues from oxidative stress (PubMed:18179478). May be involved in erythroid differentiation (PubMed:23071114).|||May interact with SMARCA4/BRG1.|||Nucleus http://togogenome.org/gene/10090:Ubn2 ^@ http://purl.uniprot.org/uniprot/Q80WC1 ^@ Similarity ^@ Belongs to the ubinuclein family. http://togogenome.org/gene/10090:Vmn1r48 ^@ http://purl.uniprot.org/uniprot/Q9EQ52 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Tiprl ^@ http://purl.uniprot.org/uniprot/Q8BH58 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TIP41 family.|||Cytoplasm|||Interacts with PPP2CA. Interacts with PPP2CB, PPP4C and PPP6C. Interacts with IGBP1; the interaction is dependent on PPP2CA. Associates with a protein phosphatase 2A PP2A(C):IGBP1 complex (By similarity). Interacts with PPP4C and PPP4R2 (PubMed:26717153).|||May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AX phosphorylated on Ser-140 (gamma-H2AX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair (By similarity). http://togogenome.org/gene/10090:Pcdhga3 ^@ http://purl.uniprot.org/uniprot/Q91XY5 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Gpm6a ^@ http://purl.uniprot.org/uniprot/P35802|||http://purl.uniprot.org/uniprot/Q542P2|||http://purl.uniprot.org/uniprot/Q8R1P3 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the myelin proteolipid protein family.|||Cell membrane|||First detected in presumptive postmitotic neurons in the developing neural tube at embryonic day 9. Expressed in 14 dpc retinas, and expression continued after birth with a slight decrease between P12 and P15. In the 14 dpc retina is mainly and strongly expressed in the NFL. In P1 and P5 retinas strong expression is confined to the IPL and also in NFL. At P10 and in the adult retina strong expression is detected in the IPL, and weak expression in NFL, OPL, and inner nuclear layer. Is expressed on postmitotic mature neurons.|||Interacts with OPRM1 (By similarity). Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction leads to palmitoylation of GPM6A (By similarity).|||Involved in neuronal differentiation, including differentiation and migration of neuronal stem cells. Plays a role in neuronal plasticity and is involved in neurite and filopodia outgrowth, filopodia motility and probably synapse formation. Gpm6a-induced filopodia formation involves mitogen-activated protein kinase (MAPK) and Src signaling pathways. Conflictingly, PubMed:22162747 reports that induced cellular protrusions are simple membrane-wrapped tubules without actin or tubulin-based cytoskeletons and with Gpm6a gliding along membrane edges indicative for a function in actin-independent membrane deformation. May be involved in neuronal NGF-dependent Ca(2+) influx. May be involved in regulation of endocytosis and intracellular trafficking of G-protein-coupled receptors (GPCRs); enhances internalization and recycling of mu-type opioid receptor.|||Membrane|||N-glycosylated.|||Palmitoylated by ZDHHC17/HIP14.|||Widely expressed in the CNS. Found especially in the granule cell layer of the cerebellum but not in the molecular layer or white matter. Expressed in the immature embryonic retina including the nerve fiber layer (NFL), inner plexiform layer (IPL), and outer plexiform layer (OPL). Weakly expressed in processes of Mueller glia cells.|||axon|||dendritic spine|||filopodium|||growth cone|||neuron projection http://togogenome.org/gene/10090:Acox3 ^@ http://purl.uniprot.org/uniprot/Q3TAW3|||http://purl.uniprot.org/uniprot/Q9EPL9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the acyl-CoA oxidase family.|||Oxidizes the CoA-esters of 2-methyl-branched fatty acids.|||Peroxisome http://togogenome.org/gene/10090:Gclc ^@ http://purl.uniprot.org/uniprot/P97494|||http://purl.uniprot.org/uniprot/Q3TEF1|||http://purl.uniprot.org/uniprot/Q3UNA7 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Belongs to the glutamate--cysteine ligase type 3 family.|||Catalyzes the ATP-dependent ligation of L-glutamate and L-cysteine and participates in the first and rate-limiting step in glutathione biosynthesis.|||Feedback inhibition by glutathione.|||Heterodimer of a catalytic heavy chain and a regulatory light chain. http://togogenome.org/gene/10090:Prap1 ^@ http://purl.uniprot.org/uniprot/Q80XD8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum|||Interacts with MTTP (PubMed:33168624). Interacts with MAD1L1 (By similarity).|||Lipid-binding protein which promotes lipid absorption by facilitating MTTP-mediated lipid transfer (mainly triglycerides and phospholipids) and MTTP-mediated apoB lipoprotein assembly and secretion (PubMed:33168624). Protects the gastrointestinal epithelium from irradiation-induced apoptosis (PubMed:32629119). May play an important role in maintaining normal growth homeostasis in epithelial cells (By similarity). Involved in p53/TP53-dependent cell survival after DNA damage (By similarity).|||Mice show an increase in the length of the small intestine (PubMed:33168624). Gain significantly less body weight and fat mass when on high-fat diets compared with littermate controls and are prevented from hepatosteatosis (PubMed:33168624). Show increased cytokine expression and altered gut microbiota, and are significantly more susceptible to oxidative insult by ionizing radiation, showing accelerated mortality and enterocyte apoptosis (PubMed:32629119).|||Predominantly expressed in the intestinal epithelial cells than in the liver (at protein level) (PubMed:33168624, PubMed:32629119). Abundantly expressed in the uterus during late pregnancy by uterus epithelial cells. After birth expression rapidly decreases and is no longer found in the uterus by the third day. Also highly expressed in the small intestine where it shows a proximal-distal graded expression.|||Secreted http://togogenome.org/gene/10090:Npc2 ^@ http://purl.uniprot.org/uniprot/Q9Z0J0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NPC2 family.|||Binds cholesterol in a hydrophobic pocket; there are no hydrogen bonds between the sterol and the protein.|||Detected in liver and bile (PubMed:21315718). Detected in epididymis (at protein level). Detected in caput epididymis, corpus epididymis, cauda epididymis and ovary (PubMed:10863096).|||Endoplasmic reticulum|||Interacts with NPC1 (via the second lumenal domain) in a cholestrol-dependent manner. Interacts with NUS1/NgBR, the interaction stabilizes NCP2 and regulates cholesterol trafficking. Interacts with DHDDS. Interacts with NEDD4L (via C2 domain). Interacts with NPC1L1.|||Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment (PubMed:12591949, PubMed:17018531, PubMed:21315718, PubMed:26296895). Unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes is transferred by NPC2 to the cholesterol-binding pocket in the N-terminal domain of NPC1. May bind and mobilize cholesterol that is associated with membranes. NPC2 binds cholesterol with a 1:1 stoichiometry. Can bind a variety of sterols, including lathosterol, desmosterol and the plant sterols stigmasterol and beta-sitosterol (By similarity). The secreted form of NCP2 regulates biliary cholesterol secretion via stimulation of ABCG5/ABCG8-mediated cholesterol transport (PubMed:21315718).|||Lysosome|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Or56b35 ^@ http://purl.uniprot.org/uniprot/Q8VG18 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem232 ^@ http://purl.uniprot.org/uniprot/Q5K6N0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Deficient mice are viable and display no apparent abnormalities. However male mice are infertile. Mice display an abnormal sperm flagellum morphology. Furthermore, mice have low sperm motility and decreased total sperm count. The sperm flagella of deficient mice have abnormalities in the cytoplasm removal and the flagella axoneme lacks microtubule doublet 7 and the corresponding ODF.|||High expression in the testis and weak expression levels in the spleen, liver, brain, uterus, lung, epididymis and kidney. Not detected in the heart or ovary.|||Membrane|||Plays a critical role for male fertility and sperm motility by regulating sperm cytoplasm removal and maintaining axoneme integrity. http://togogenome.org/gene/10090:Bbs12 ^@ http://purl.uniprot.org/uniprot/Q5SUD9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family. BBS12 subfamily.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with MKKS.|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Involved in adipogenic differentiation.|||cilium http://togogenome.org/gene/10090:Gabarap ^@ http://purl.uniprot.org/uniprot/Q9DCD6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATG8 family.|||Cytoplasmic vesicle|||Endomembrane system|||Golgi apparatus membrane|||Interacts with GPHN (PubMed:10900017). Interacts with NSF (By similarity). Interacts with ATG7 (PubMed:11890701). Interacts with ATG3 and ATG13 (By similarity). Interacts with alpha-tubulin (By similarity). Interacts with beta-tubulin (PubMed:10899939). Interacts with GABRG2 (By similarity). Interacts with RB1CC1 (By similarity). Interacts with ULK1 (By similarity). Interacts with CALR (By similarity). Interacts with DDX47 (By similarity). Interacts with TP53INP1 and TP53INP2 (By similarity). Interacts with TBC1D5 (By similarity). Interacts with TBC1D25 (PubMed:21383079). Directly interacts with SQSTM1 (By similarity). Interacts with MAPK15 (By similarity). Interacts with TECPR2 (By similarity). Interacts with PCM1 (By similarity). Interacts with TRIM5 and TRIM21 (By similarity). Interacts with MEFV (By similarity). Interacts with KIF21B (By similarity). Interacts with WDFY3; this interaction is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies (By similarity). Interacts with FLCN; interaction regulates autophagy (By similarity). Interacts with UBA5 (By similarity). Interacts with KBTBD6 and KBTBD7; the interaction is direct and required for the ubiquitination of TIAM1 (By similarity). Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3 (By similarity). Interacts with Irgm1 (By similarity). Interacts with STX17 (By similarity). Interacts with CT55; this interaction may be important for GABARAP protein stability (By similarity).|||The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, GABARAP-I (PubMed:14530254). The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, GABARAP-II (By similarity). During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid (By similarity). ATG4 proteins also mediate the delipidation of PE-conjugated forms (PubMed:33795848). In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy (By similarity). ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (PubMed:33795848).|||Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in autophagy: while LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. Also required for the local activation of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor (GEF) that activates RAC1 and downstream signal transduction. Thereby, regulates different biological processes including the organization of the cytoskeleton, cell migration and proliferation. Involved in apoptosis.|||autophagosome membrane|||cytoskeleton http://togogenome.org/gene/10090:Cops7b ^@ http://purl.uniprot.org/uniprot/Q8BV13 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CSN7/EIF3M family. CSN7 subfamily.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively (By similarity).|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B) and COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS5, COPS6 and COPS8. Interacts with EIF3S6 (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Tas2r113 ^@ http://purl.uniprot.org/uniprot/Q7M711 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Adam6a ^@ http://purl.uniprot.org/uniprot/B2RSY5 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Hfm1 ^@ http://purl.uniprot.org/uniprot/D3Z4R1 ^@ Disruption Phenotype|||Function|||Similarity ^@ Belongs to the helicase family. SKI2 subfamily.|||Male and female mutants are sterile due to severe blockage of spermatogenesis and oogenesis.|||Required for crossover formation and complete synapsis of homologous chromosomes during meiosis. http://togogenome.org/gene/10090:Cpeb1 ^@ http://purl.uniprot.org/uniprot/P70166|||http://purl.uniprot.org/uniprot/Q059Z2 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM CPEB family.|||Cytoplasm|||Cytoplasmic granule|||Expressed in embryonic ovaries at 14.5, 16.5 and 18.5 dpc (at protein level).|||Expressed in hippocampus, cerebral cortex and oocytes (at protein level). Expressed in brain, heart, kidney, lung and ovary and testis. Weakly expressed in granular cells of dentate gyrus and the pyramidal cells of CA3 and CA1 of the hippocampus.|||Interacts with kinesin, dynein, APLP1, APLP2, TENT2/GLD2 and APP. Both phosphorylated and non phosphorylated forms interact with APLP1 (PubMed:12629046, PubMed:16314516, PubMed:16705177, PubMed:17927953). Interacts with TENT4B; the interaction is required for TENT4B-mediated translational control (By similarity).|||Membrane|||Not induced by kainate.|||P-body|||Phosphorylated on serine/threonine residues by AURKA within positions 165 and 196 (By similarity). Phosphorylation and dephosphorylation on Thr-171 regulates cytoplasmic polyadenylation and translation of CPE-containing mRNAs. Phosphorylation on Thr-171 by AURKA in embryonic ovaries at 16.5 dpc (mostly pachytene oocytes) activates CPEB1. Not phosphorylated on Thr-171 in embryonic ovaries between 18.5 dpc (diplotene oocytes) and metaphase I. Dephosphorylation on Thr-171 by PP1 in embryonic ovaries at 18.5 dpc (mostly diplotene oocytes) inactivates CPEB1. In maturing oocytes, re-phosphorylation on Thr-171 by AURKA reactivates CPEB1. Phosphorylation on Thr-171 by CAMK2A in depolarized hippocampal neurons activates CPEB1. Dephosphorylation on Thr-171 (indirectly by PP1) in hippocampal neurons inactivates CPEB1. Phosphorylation on Thr-171 may be promoted by APLP1. Phosphorylation increases binding to RNA.|||Postsynaptic density|||Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation, early development and at postsynapse sites of neurons. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the 3'-UTR of mRNAs. In absence of phosphorylation and in association with TACC3 is also involved as a repressor of translation of CPE-containing mRNA; a repression that is relieved by phosphorylation or degradation (By similarity). Involved in the transport of CPE-containing mRNA to dendrites; those mRNAs may be transported to dendrites in a translationally dormant form and translationally activated at synapses. Its interaction with APLP1 promotes local CPE-containing mRNA polyadenylation and translation activation. Induces the assembly of stress granules in the absence of stress (By similarity). Required for cell cycle progression, specifically for prophase entry (By similarity).|||Synapse|||The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA. The interdomain linker (411-429) acts as a hinge to fix the relative orientation of the 2 RRMs. The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs. A continuous hydrophobic interface is formed between the 2 RRM. http://togogenome.org/gene/10090:Cd83 ^@ http://purl.uniprot.org/uniprot/O88324 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in spleen and brain, but is also detected in most tissues analyzed.|||May play a significant role in antigen presentation or the cellular interactions that follow lymphocyte activation.|||Membrane|||Monomer. http://togogenome.org/gene/10090:Il31 ^@ http://purl.uniprot.org/uniprot/Q6EAL8 ^@ Function|||Miscellaneous|||Subcellular Location Annotation ^@ Activates STAT3 and possibly STAT1 and STAT5 through the IL31 heterodimeric receptor composed of IL31RA and OSMR (PubMed:15184896). May function in skin immunity (PubMed:15184896). Enhances myeloid progenitor cell survival in vitro (PubMed:17379091). Induces RETNLA and serum amyloid A protein expression in macrophages (PubMed:25847241).|||Il31 transgenic mice develop dermatitis. A similar phenotype is caused by local delivery of Il31.|||Secreted http://togogenome.org/gene/10090:Max ^@ http://purl.uniprot.org/uniprot/P28574 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAX family.|||By serum; in 3T3 fibroblasts.|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MYC or MAD. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with SPAG9. The heterodimer MYC:MAX interacts with ABI1; the interaction may enhance MYC:MAX transcriptional activity.|||Nucleus|||Phosphorylated.|||Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC:MAX complex is a transcriptional activator, whereas the MAD:MAX complex is a repressor. CpG methylation of the recognition site greatly inhibits DNA binding, suggesting that DNA methylation may regulate the MYC:MAX complex in vivo. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 'Lys-9' histone methyltransferase activity. Represses MYC transcriptional activity from E-box elements (By similarity).|||dendrite http://togogenome.org/gene/10090:Prdm11 ^@ http://purl.uniprot.org/uniprot/A2AGX3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Cytoplasm|||May be involved in transcription regulation.|||Mutant mice are born in expected Mendelian ratios and exhibit no apparent phenotype. Mutant embryonic fibroblasts show an increased oncogenic transformation capacity.|||Nucleus|||Widely expressed, with the highest levels in spleen, lung, mesenteric lymph node and kidney. Among splenocytes, predominantly expressed by B-cells (at protein level). http://togogenome.org/gene/10090:Znrf3 ^@ http://purl.uniprot.org/uniprot/Q5SSZ7 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZNRF3 family.|||Cell membrane|||During limb development, at 14.5 dpc, ubiquitously expressed in the limb bud. In developing lungs, at 14.5 dpc, ubiquitously expressed.|||E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components Frizzled and LRP6. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby restricting the size of the intestinal stem cell zone (PubMed:22575959, PubMed:22895187). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (By similarity).|||Embryos die around birth due to activation of Wnt signaling pathway. Embryos display a lack of lens formation due to Wnt activation. Conditional knockout mice lacking both Rnf43 and Znrf3 in intestine show a marked expansion of the proliferative compartment, resembling the effects of acute deletion of Apc.|||Interacts with LRP6, FZD4, FZD5, FZD6 and FZD8 (By similarity). Interacts with RSPO1; interaction promotes indirect interaction with LGR4 and membrane clearance of ZNRF3 (By similarity). Interacts with LMBR1L (PubMed:31073040).|||Negatively regulated by R-spondin proteins such as RSPO1: interaction with RSPO1 induces the indirect association between ZNRF3 and LGR4, promoting membrane clearance of ZNRF3. http://togogenome.org/gene/10090:Or11g24 ^@ http://purl.uniprot.org/uniprot/E9Q1P0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Acvr1c ^@ http://purl.uniprot.org/uniprot/A2AJR5|||http://purl.uniprot.org/uniprot/Q3V348|||http://purl.uniprot.org/uniprot/Q8K348 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Binds the type 2 receptor protein ACVR2A.|||Expressed in interdigital regions in developing limb buds.|||Membrane|||Serine/threonine protein kinase which forms a receptor complex on ligand binding. The receptor complex consisting of 2 type II and 2 type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators, SMAD2 and SMAD3. Receptor for activin AB, activin B and NODAL. Plays a role in cell differentiation, growth arrest and apoptosis. http://togogenome.org/gene/10090:Idh3g ^@ http://purl.uniprot.org/uniprot/P70404|||http://purl.uniprot.org/uniprot/Q3TGZ3 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the isocitrate and isopropylmalate dehydrogenases family.|||Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) ion per subunit.|||Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.|||Mitochondrion|||Regulatory subunit which plays a role in the allosteric regulation of the enzyme catalyzing the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal activity but the full activity of the heterotetramer (containing two subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly and cooperative function of both heterodimers.|||The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits. http://togogenome.org/gene/10090:9530068E07Rik ^@ http://purl.uniprot.org/uniprot/Q8K201 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Oas1f ^@ http://purl.uniprot.org/uniprot/Q14AZ4 ^@ Similarity ^@ Belongs to the 2-5A synthase family. http://togogenome.org/gene/10090:Helb ^@ http://purl.uniprot.org/uniprot/Q6NVF4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 5'-3' DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection (PubMed:26774285). Recruitment to single-stranded DNA (ssDNA) following DNA damage leads to inhibit the nucleases catalyzing resection, such as EXO1, BLM and DNA2, possibly via the 5'-3' ssDNA translocase activity of HELB (PubMed:26774285). As cells approach S phase, DNA end resection is promoted by the nuclear export of HELB following phosphorylation (PubMed:26774285). Acts independently of TP53BP1 (PubMed:26774285). Unwinds duplex DNA with 5'-3' polarity. Has single-strand DNA-dependent ATPase and DNA helicase activities. Prefers ATP and dATP as substrates. During S phase, may facilitate cellular recovery from replication stress (PubMed:11557815, PubMed:7596831, PubMed:7794903).|||Belongs to the RecD family. HELB subfamily.|||Binds to RPA1; this interaction promotes HELB recruitment to chromatin following DNA damage. Interacts with at least two subunits of the DNA polymerase alpha complex. Interacts with CDC45. Interacts with TOPB1.|||Chromosome|||Cytoplasm|||Nucleus|||Phosphorylated at Ser-942 by CDK2 during the G1/S transition, resulting in its nuclear export into the cytoplasm. As S phase progresses, its exclusion from the nucleus promotes the activation of long-range resection. http://togogenome.org/gene/10090:Mthfd2l ^@ http://purl.uniprot.org/uniprot/D3YZG8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.|||Bifunctional mitochondrial folate-interconverting enzyme that has both NAD/NADP-dependent methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities.|||Expressed at all embryonic days examined in the neural tube and the forebrain, midbrain, and hindbrain. Also detected in the branchial arches and limb buds, particularly along the progress zone. Expression is low at 8.5 dpc but increases at 10.5 dpc.|||Mitochondrion inner membrane|||Widely expressed. http://togogenome.org/gene/10090:Aqp7 ^@ http://purl.uniprot.org/uniprot/O54794|||http://purl.uniprot.org/uniprot/Q5DX24 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro/Ala-Ala/Ser (NPA).|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Detected in proximal tubules in kidney (PubMed:15998844, PubMed:17077387). Detected in the capillary network between muscle fibers in skeletal muscle and heart, and in spermatids and on spermatozoa tails in testis and epididymis (PubMed:17077387). Detected in white and brown adipose tissue, especially on small blood vessels (at protein level) (PubMed:15591341, PubMed:17077387, PubMed:25643985). Detected in kidney and white adipose tissue (PubMed:15746100).|||Forms a channel that mediates water and glycerol transport across cell membranes at neutral pH (PubMed:15591341, PubMed:15746100, PubMed:16009937). The channel is also permeable to urea (By similarity). Plays an important role in body energy homeostasis under conditions that promote lipid catabolism, giving rise to glycerol and free fatty acids (PubMed:15591341, PubMed:16009937). Mediates glycerol export from adipocytes (PubMed:15591341, PubMed:15746100, PubMed:16009937). After release into the blood stream, glycerol is used for gluconeogenesis in the liver to maintain normal blood glucose levels and prevent fasting hypoglycemia (PubMed:15591341). Required for normal glycerol reabsorption in the kidney (PubMed:15998844, PubMed:17077387).|||Homotetramer. Interacts (via N-terminus) with PLIN1.|||Lipid droplet|||Membrane|||Young mutant mice appear normal and are fertile (PubMed:16009937, PubMed:17077387). However, they start to become obese after about 12 weeks and display enlarged adipocytes (PubMed:15746100, PubMed:16009937). The effects on plasma glycerol levels vary between experiments; some reports find no significant difference in plasma glycerol levels in fed animals (PubMed:15746100, PubMed:15998844, PubMed:17077387). Others report decreased plasma glycerol levels in fed animals (PubMed:15591341). After fasting, mutant mice display lower plasma glycerol levels than wild-type, and increased glycerol content in their adipose tissue (PubMed:15591341, PubMed:16009937). After fasting, mutant mice display lower blood glucose levels than wild-type (PubMed:15591341). Mutant mice display strongly increased glycerol levels in urine (PubMed:15998844, PubMed:17077387). Water permeability of brush border membranes is slightly reduced, but urinary concentrating ability is not altered (PubMed:15998844).|||cell cortex http://togogenome.org/gene/10090:Sdk2 ^@ http://purl.uniprot.org/uniprot/Q6V4S5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adhesion molecule that promotes lamina-specific synaptic connections in the retina and is specifically required for the formation of neuronal circuits that detect motion (PubMed:26287463). Acts by promoting formation of synapses between two specific retinal cell types: the retinal ganglion cells W3B-RGCs and the excitatory amacrine cells VG3-ACs. Formation of synapses between these two cells plays a key role in detection of motion (PubMed:26287463). Promotes synaptic connectivity via homophilic interactions (PubMed:26287463).|||Belongs to the sidekick family.|||Cell membrane|||Due to intron retention.|||Expressed in retinal ganglion cells (RGCs) that form synapses in distinct inner plexiform layer (IPL) sublaminae. Specifically expressed in specific subsets of retinal ganglion cells (RGCs), named W3B-RGCs, that specifically respond when the timing of the movement of a small object differs from that of the background, but not when they coincide (at protein level). Also present in excitatory amacrine cell type called VG3-ACs, that provide strong and selective input W3B-RGCs (at protein level) (PubMed:26287463). Expressed at low levels in the glomeruli (PubMed:15213259).|||Highly expressed in many fetal tissues, inlcuding kidney but shows markedly lower expression in adult organs. Expression in kidney is high throughout development with maximal expression occurring near birth.|||Homodimer; mediates homophilic interactions to promote cell adhesion (PubMed:15703275, PubMed:26287463). Interacts (via PDZ-binding motif) with MAGI1, MAGI2, DLG2, DLG3 and DLG4 (PubMed:20219992).|||Mice are viable and fertile but show decreased synaptic connectivity between the retinal ganglion cells W3B-RGCs and the excitatory amacrine cells VG3-ACs.|||Synapse|||the PDZ-binding motif mediates interaction with PDZ domain-containing proteins MAGI1, MAGI2, DLG2, DLG3 and DLG4 and is required for is required for synaptic localization in photoreceptors. http://togogenome.org/gene/10090:Slc25a2 ^@ http://purl.uniprot.org/uniprot/Q99ML6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Membrane http://togogenome.org/gene/10090:Sec22c ^@ http://purl.uniprot.org/uniprot/Q8BXT9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptobrevin family.|||Endoplasmic reticulum membrane|||May be involved in vesicle transport between the ER and the Golgi complex. http://togogenome.org/gene/10090:Gm4565 ^@ http://purl.uniprot.org/uniprot/A0A140LJ87 ^@ Similarity ^@ Belongs to the protein kinase superfamily. http://togogenome.org/gene/10090:Lpp ^@ http://purl.uniprot.org/uniprot/Q8BFW7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the zyxin/ajuba family.|||Cell junction|||Cytoplasm|||Fusion protein carrying the DNA-binding domains of HMGA2/HMGIC and the LIM domain of LPP causes malignant transformation of NIH3T3 cells.|||Interacts with VASP, with PDZ domains of SCRIB and with ACTN1/alpha-actinin.|||May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus (By similarity).|||Nucleus http://togogenome.org/gene/10090:Slc14a1 ^@ http://purl.uniprot.org/uniprot/Q8VHL0 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the urea transporter family.|||Cell membrane|||Down-regulated by water deprivation in urinary bladder and ureter, but not in kidney medulla, colon, testis nor brain.|||Expressed in brain, kidney, heart, liver, lung, skeletal muscle, spleen, testis, ureter and urinary bladder (at protein level). Along the gastrointestinal tract, detected in colon, jejunum and stomach (at protein level). In the kidney, expressed in some microvessels of the inner and outer medulla, but not all (at protein level). Not detected in the cortex (at protein level). Detected in the urothelium all along the urinary tract, including the papilla surface, the ureter, the bladder and the urethra (at protein level). In the brain, expressed at the border of the corpus callosum and striatum in astrocytic cellular processes surrounding blood microvessels (at protein level). Detected in erythrocytes (at protein level).|||Homotrimer; each subunit contains a pore through which urea permeates (By similarity). Identified in a complex with STOM (By similarity).|||Mediates the transport of urea driven by a concentration gradient across the cell membranes of erythrocytes and the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism (PubMed:11792714). Facilitates water transport in erythrocytes (PubMed:12133842).|||Mutant mice exhibit grossly normal appearance, activity and behavior. Plasma sodium, potassium, chloride, bicarbonate and creatinine concentrations, as well as hematocrit, are similar to wild type animals. Urea permeability in erythrocytes is 45-fold lower than that from wild-type mice. Daily urine output is 1.5-fold greater and urine osmolarity is lower than in wild-type mice. After 24 hours of water deprivation, plasma urea concentration is 30% higher and urine urea concentration 35% lower in mutant mice than in wild-type animals. Mice lacking both Aqp1 and Slc14a1 are born at the expected Mendelian ratio, but do not thrive; half of them die within ten days after birth and none are alive after two weeks. Urine osmolality is somewhat lower than that observed with mice lacking Aqp1. Besides, erythrocyte water permeability is significantly lower than in mice lacking only Aqp1.|||N-glycosylated in red blood cells, as well as in most non-erythroid tissues, except in the gastrocnemius muscle and in the gastrointestinal tract, including liver, colon and stomach. http://togogenome.org/gene/10090:Hexa ^@ http://purl.uniprot.org/uniprot/P29416 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Addition of GM2A stimulates the hydrolysis of sulfated glycosphingolipid SM2 and the ganglioside GM2.|||Belongs to the glycosyl hydrolase 20 family.|||Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides. The isozyme S is as active as the isozyme A on the anionic bis-sulfated glycans, the chondroitin-6-sulfate trisaccharide (C6S-3), and the dermatan sulfate pentasaccharide, and the sulfated glycosphingolipid SM2. The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide. Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A.|||Lysosome|||There are 3 beta-hexosaminidase isozymes: isozyme A (hexosaminidase A) is an heterodimer composed of one subunit alpha and one subunit beta (chain A and B); isozyme B (hexosaminidase B) is an homodimer of two beta subunits (two chains A and B); isozyme S (hexosaminidase S) is a homodimer of two alpha subunits. The composition of the dimer (isozyme A versus isozyme S) has a significant effect on the substrate specificity of the alpha subunit active site.|||Ubiquitous. Most abundant in testis, adrenal, epididymis and heart. Low levels seen in the liver. http://togogenome.org/gene/10090:Vmn1r37 ^@ http://purl.uniprot.org/uniprot/Q8R2E4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myh4 ^@ http://purl.uniprot.org/uniprot/Q3UUB1|||http://purl.uniprot.org/uniprot/Q5SX39 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).|||Muscle contraction.|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||Represents a conventional myosin. This protein should not be confused with the unconventional myosin-4 (MYO4).|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||myofibril http://togogenome.org/gene/10090:Foxm1 ^@ http://purl.uniprot.org/uniprot/Q6P1H7 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Or8b46 ^@ http://purl.uniprot.org/uniprot/Q8VG76 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pknox1 ^@ http://purl.uniprot.org/uniprot/O70477 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) In complex with PBX1, binds to the 5'-TGATTGAC-3' consensus sequence in the U5 region of Moloney murine leukemia virus and promotes viral transcription.|||Activates transcription in the presence of PBX1A and HOXA1.|||Belongs to the TALE/MEIS homeobox family.|||Interacts with MN1.|||Nucleus http://togogenome.org/gene/10090:Ccnk ^@ http://purl.uniprot.org/uniprot/Q3U3M5 ^@ Similarity ^@ Belongs to the cyclin family. http://togogenome.org/gene/10090:Or8c13 ^@ http://purl.uniprot.org/uniprot/E9Q843 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Arl15 ^@ http://purl.uniprot.org/uniprot/Q8BGR6 ^@ Similarity ^@ Belongs to the small GTPase superfamily. Arf family. http://togogenome.org/gene/10090:Coq6 ^@ http://purl.uniprot.org/uniprot/Q8R1S0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, expressed in the metanephric mesenchyme. At 16.5 dpc, expressed in the condensing metanephric mesenchyme surrounding the ureter tips. At 18.5 dpc, expressed in whole kidney.|||Belongs to the UbiH/COQ6 family.|||Cell projection|||Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with COQ8B and COQ7.|||Expressed in the kidney, in podocytes.|||FAD-dependent monooxygenase required for the C5-ring hydroxylation during ubiquinone biosynthesis. Catalyzes the hydroxylation of 3-polyprenyl-4-hydroxybenzoic acid to 3-polyprenyl-4,5-dihydroxybenzoic acid. The electrons required for the hydroxylation reaction may be funneled indirectly from NADPH via a ferredoxin/ferredoxin reductase system to COQ6.|||Golgi apparatus|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Sh3pxd2a ^@ http://purl.uniprot.org/uniprot/O89032 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide (By similarity).|||Belongs to the SH3PXD2 family.|||Cytoplasm|||Interacts with ADAM12, ADAM15 and ADAM19 (By similarity). Interacts with NOXO1 (By similarity). Interacts (via SH3 domains) with NOXA1; the interaction is direct (By similarity). Interacts (via N-terminus) with CYBA. Interacts with FASLG (By similarity).|||Shows significant decrease in total cellular reactive oxygen species (ROS) and in podosome formation.|||The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity).|||The fifth SH3 domain mediates binding with ADAM12, ADAM15 and ADAM19.|||Tyrosine phosphorylated by SRC. Phosphorylation plays a regulatory role in the protein localization. The intramolecular interaction of the PX domain with the third SH3 domain maintains the protein in the cytoplasm and phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region. Phosphorylated on serine upon DNA damage, probably by ATM or ATR (By similarity).|||Widely expressed. Not found in the spleen and testis.|||podosome http://togogenome.org/gene/10090:Cdkl5 ^@ http://purl.uniprot.org/uniprot/Q3UTQ8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Interacts with MECP2.|||Mediates phosphorylation of MECP2. May regulate ciliogenesis.|||Nucleus|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Itk ^@ http://purl.uniprot.org/uniprot/A1A560|||http://purl.uniprot.org/uniprot/Q03526|||http://purl.uniprot.org/uniprot/Q3U5G1|||http://purl.uniprot.org/uniprot/Q5STT8 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Homooligomerizes; this association negatively regulates kinase activity. Interacts with PPIA/CYPA; this interaction regulates TCR signal strength via a proline-directed conformational switch in ITK. Interacts with THEMIS (By similarity). Interacts with FASLG. Interacts with VAV1; this interaction is important for VAV1 localization and TCR-induced actin polarization. Interacts with TBX21 (PubMed:15662016).|||Is detected in the thymus, lymph node and very faintly in the spleen, but is not detected in the liver, lung, kidney, heart, brain, intestine or testis. Expressed in T-lymphocytes and mast cells. It may also be expressed in natural killer cells.|||Is present in the fetal thymus as early as day 14 of gestation. The levels are 5- to 10-fold higher in thymocytes than in peripheral T-cells, and increase in the thymus during development from neonate to adult.|||Mice display decreased mature thymocytes and elicit profound defect in CD4+ and CD8+ T-cell development (PubMed:8777721, PubMed:10213685, PubMed:16860760, PubMed:21036902). Additionally, they show a strong decrease of cytokine production in response to TCR receptor stimulation (PubMed:21036902). Impaired TCR-mediated calcium response in gamma-delta T-cells (PubMed:23562159). Loss of Vgamma2-positive immature thymocyte-specific transcriptomic profile, although there is no change to overall transcription factor expression levels (PubMed:23562159). Not required for the generation of IL17A expressing gamma-delta T-cells (PubMed:23562159).|||Nucleus|||Phosphorylated at Tyr-517 in the activation loop of the kinase domain by LCK. Subsequent autophosphorylation at Tyr-186 leads to the kinase activation. The autophosphorylated Tyr-186 lies within the substrate binding sequence of the SH3 domain (By similarity).|||The N-terminal PH domain allows ITK to be recruited to the plasma membrane by an activated PI3 kinase. This domain contains also a proline-rich region (PRR). The adjoining domain is a SH3 domain, which binds to PRR (from itself or from other proteins). Next, a SH2 domain is required for binding tyrosine-phosphorylated substrates. In the C-terminal region, the kinase domain is required for tyrosine phosphorylation (By similarity).|||Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors.|||Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (PubMed:23562159). Phosphorylates TBX21 at 'Tyr-525' and mediates its interaction with GATA3 (PubMed:15662016).|||Ubiquitinated. http://togogenome.org/gene/10090:Rgs7bp ^@ http://purl.uniprot.org/uniprot/Q8BQP9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RGS7BP/RGS9BP family.|||Cell membrane|||Cytoplasm|||Interacts with 'R7' family proteins RGS6, RGS7, RGS9 and RGS11. Component of some R7-Gbeta5 complex composed of some R7 protein (RGS6, RGS7, RGS9 or RGS11), Gbeta5 (GNB5) and RGS7BP.|||Nucleus|||Palmitoylated (PubMed:15897264, PubMed:16574655, PubMed:21343290). Undergoes rapid palmitoylation turnover (PubMed:21343290). De novo and turnover palmitoylation are both mediated by ZDHHC2 (PubMed:21343290). Palmitoylation regulates the cell membrane and nuclear shuttling and the regulation of GPCR signaling (PubMed:15897264, PubMed:16574655, PubMed:16867977, PubMed:21343290). Upon depalmitoylation, it is targeted from the plasma membrane into the nucleus (PubMed:15897264, PubMed:16574655). GPCR signaling inhibits depalmitoylation and promotes localization to the plasma membrane (PubMed:21343290).|||Regulator of G protein-coupled receptor (GPCR) signaling. Regulatory subunit of the R7-Gbeta5 complexes that acts by controlling the subcellular location of the R7-Gbeta5 complexes. When palmitoylated, it targets the R7-Gbeta5 complexes to the plasma membrane, leading to inhibit G protein alpha subunits. When it is unpalmitoylated, the R7-Gbeta5 complexes undergo a nuclear/cytoplasmic shuttling. May also act by controlling the proteolytic stability of R7 proteins, probably by protecting them from degradation.|||Specifically expressed in the central nervous system including the retina but not in other non-neuronal tissues (at protein level).|||The nuclear localization signal is both required for nuclear localization and palmitoylation. http://togogenome.org/gene/10090:Crym ^@ http://purl.uniprot.org/uniprot/O54983 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ornithine cyclodeaminase/mu-crystallin family.|||Cytoplasm|||Homodimer.|||Specifically catalyzes the reduction of imine bonds in brain substrates that may include cystathionine ketimine (CysK) and lanthionine ketimine (LK). Binds thyroid hormone which is a strong reversible inhibitor. Presumably involved in the regulation of the free intracellular concentration of triiodothyronine and access to its nuclear receptors (By similarity). http://togogenome.org/gene/10090:Igfals ^@ http://purl.uniprot.org/uniprot/P70389 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Forms a ternary complex of about 140 to 150 kDa with IGF-I or IGF-II and IGFBP-3.|||May have an important role in regulating the access of circulating IGFs to the tissues.|||extracellular space http://togogenome.org/gene/10090:N4bp2l2 ^@ http://purl.uniprot.org/uniprot/Q8JZS6 ^@ Miscellaneous ^@ Due to a partial intron retention. http://togogenome.org/gene/10090:Rhof ^@ http://purl.uniprot.org/uniprot/Q8BYP3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Causes the formation of thin, actin-rich surface projections called filopodia. Functions cooperatively with CDC42 and Rac to generate additional structures, increasing the diversity of actin-based morphology (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:E2f1 ^@ http://purl.uniprot.org/uniprot/Q547J6|||http://purl.uniprot.org/uniprot/Q61501|||http://purl.uniprot.org/uniprot/Q9CYB4 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation stimulates DNA-binding. Enhanced under stress conditions such as DNA damage and inhibited by retinoblastoma protein RB1. Regulated by KAP1/TRIM28 which recruits HDAC1 to E2F1 resulting in deacetylation. Acetylated by P/CAF/KAT2B (By similarity).|||BIRC2/c-IAP1 stimulates its transcriptional activity.|||Belongs to the E2F/DP family.|||Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F1 complex binds specifically hypophosphorylated retinoblastoma protein RB1 (PubMed:8336704). During the cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering E2F transcriptionally active. Interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation. Binds TOPBP1 and EAPP. Interacts with ARID3A. Interacts with TRIM28; the interaction inhibits E2F1 acetylation through recruiting HDAC1 and represses its transcriptional activity. Interaction with KAT2B; the interaction acetylates E2F1 enhancing its DNA-binding and transcriptional activity. Interacts with BIRC2/c-IAP1 (via BIR domains). The complex TFDP1:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target genes promoters and represses its transcriptional activity. Interacts with RRP1B (By similarity). Interacts with HCFC1 (By similarity). Interacts with KMT2E; the interaction is probably indirect and is mediated via HCFC1 (By similarity). Interacts with DCAF5 and L3MBTL3; the interaction requires methylation at Lys-180 and is necessary to target E2F1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex (By similarity).|||In the developing nervous system, first detected in the neural tube at 9.5 dpc. By 10.5 dpc, levels increase throughout the brain, with highest levels in the hindbrain and in the spinal cord, expressed only in the rostral half. By 11.5 dpc, expression found throughout the brain and spinal cord. From 12.5 dpc, expression restricted to the ventricular regions of the brain, peaks at 13.5 dpc and declines thereafter. Only weak expression in the developing spinal cord from 11.5-16.5 dpc. In the developing retina, expression is confined to the undifferentiated retinoblastic cell layer. In other developing tissues, E2F1 is expressed in kidney, lung, liver hepatocytes, heart and thymus. Highest levels in liver. Absent in choroid plexus.|||Methylation at Lys-180 by SETD7 promotes E2F1 ubiquitin-dependent proteasomal degradation.|||Nucleus|||Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase. Phosphorylation by CHEK2 stabilizes E2F1 upon DNA damage and regulates its effect on transcription and apoptosis. Phosphorylation at Ser-396 by GSK3B promotes interaction with USP11, leading to its deubiquitination and stabilization.|||Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication (PubMed:11672531, PubMed:20176812, PubMed:9674698). The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase (By similarity). E2F1 binds preferentially RB1 in a cell-cycle dependent manner (By similarity). It can mediate both cell proliferation and TP53/p53-dependent apoptosis (PubMed:9674698). Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:11672531, PubMed:20176812). Directly activates transcription of PEG10 (By similarity). Positively regulates transcription of RRP1B (By similarity).|||Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its degradation. Deubiquitinated by USP11 follwong phosphorylation by GSK3B, promoting its stability. http://togogenome.org/gene/10090:Pcdhgb2 ^@ http://purl.uniprot.org/uniprot/Q91XX7 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Or8b57 ^@ http://purl.uniprot.org/uniprot/Q8VG90 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ppt1 ^@ http://purl.uniprot.org/uniprot/O88531|||http://purl.uniprot.org/uniprot/Q3TEL0|||http://purl.uniprot.org/uniprot/Q3U6J9|||http://purl.uniprot.org/uniprot/Q3U6W3 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the palmitoyl-protein thioesterase family.|||Expressed in the retina at a higher level than that in the brain at all developmental stages and this high level of expression in the retina is detectable much earlier than that in the brain (at protein level).|||Glycosylated.|||Highest level in testis and kidney, lower in heart, brain and lung and lowest in skeletal muscle.|||Interacts with CLN5, ATP5F1A and ATP5F1B (PubMed:19941651).|||Lysosome|||Removes thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. Prefers acyl chain lengths of 14 to 18 carbons.|||Secreted http://togogenome.org/gene/10090:Ap1s1 ^@ http://purl.uniprot.org/uniprot/P61967 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).|||Belongs to the adaptor complexes small subunit family.|||Cytoplasmic vesicle membrane|||Detected in brain and embryonic stem cells.|||Golgi apparatus|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.|||clathrin-coated pit http://togogenome.org/gene/10090:Lgi3 ^@ http://purl.uniprot.org/uniprot/Q3V1R3|||http://purl.uniprot.org/uniprot/Q8K406 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain.|||Interacts with STX1A.|||LGI3-null mice are fertile, have a normal lifespan, and do not show obvious behavioral abnormalities. They show strongly reduced expression and mislocalization of Kv1 channel complexes that infringe on the paranodal domain. Kv1 channel complexes mislocalization is further exacerbated following nerve injury, as Kv1 complexes are confined to the paranodal domain in remyelinated axons.|||May participate in the regulation of neuronal exocytosis.|||Secreted|||axon|||synaptic vesicle|||synaptosome http://togogenome.org/gene/10090:Bin3 ^@ http://purl.uniprot.org/uniprot/Q9JI08 ^@ Function|||Subcellular Location Annotation ^@ Involved in cytokinesis and septation where it has a role in the localization of F-actin.|||cytoskeleton http://togogenome.org/gene/10090:Or52ab7 ^@ http://purl.uniprot.org/uniprot/Q7TRR2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dnaaf5 ^@ http://purl.uniprot.org/uniprot/B9EJR8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNAAF5 family.|||Cytoplasm|||Cytoplasmic granule|||Cytoplasmic protein involved in the delivery of the dynein machinery to the motile cilium. It is required for the assembly of the axonemal dynein inner and outer arms, two structures attached to the peripheral outer doublet A microtubule of the axoneme, that play a crucial role in cilium motility.|||Enriched in tissues with differentiating ciliated cells including 18.5 dpc trachea and bronchus.|||Expressed in ciliated cells including ependymal cells lining the lateral ventricles and multiciliated epithelium of oviduct ampulla.|||Interacts with DNAI2; probably involved in outer arm dynein assembly. http://togogenome.org/gene/10090:Cdc42bpa ^@ http://purl.uniprot.org/uniprot/E9PVY0|||http://purl.uniprot.org/uniprot/H7BX44|||http://purl.uniprot.org/uniprot/Q3UU96 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.|||Cytoplasm|||Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42. Forms a tripartite complex with MYO18A and LRP35A with the latter acting as an adapter connecting CDC42BPA and MYO18A. LRP35A binding results in activation of CDC42BPA by abolition of its negative autoregulation. Interacts with LURAP1 (By similarity). Interacts (via AGC-kinase C-terminal domain) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with FAM89B/LRAP25 and LIMK1 (PubMed:25107909).|||Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation. Inhibited by chelerythrine chloride (By similarity).|||Proteolytically cleaved by caspases upon apoptosis induction. The cleavage at Asp-478 by CASP3 increases its kinase activity (in vitro).|||Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2. In concert with MYO18A and LRP35A, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Phosphorylates: PPP1R12A and LIMK2. May play a role in TFRC-mediated iron uptake (By similarity). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (PubMed:25107909). Triggers the formation of an extrusion apical actin ring required for epithelial extrusion of apoptotic cells (By similarity).|||lamellipodium http://togogenome.org/gene/10090:Serpinb6c ^@ http://purl.uniprot.org/uniprot/Q6P6K7|||http://purl.uniprot.org/uniprot/W4VSP4 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Slc17a8 ^@ http://purl.uniprot.org/uniprot/D3YTT3|||http://purl.uniprot.org/uniprot/Q3UE85|||http://purl.uniprot.org/uniprot/Q8BFU8 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.|||Cell membrane|||Expressed in restricted areas of the brain. Highest expression is found in the neurons of the basal forebrain, the hippocampal formation, and the majority of the neurons of the mesencephalic raphe nuclei. Expressed in inner hair cells of the ear.|||Expression peaks at P7 in the brain. Expressed in inner hair cells from 19 dpc onwards.|||Membrane|||Mice are hyperactive and suffer from intermittent, spontaneous cortical seizures. They exhibit reduced cholinergic transmission in the ventral portion of the striatum and defective acetylcholine release. They are hypersensitive to cocaine and less prone to haloperidol-induced catalepsy.|||Mice defective in Slc17a8 are profoundly deaf owing to the absence of glutamate release from hair cells at the first synapse in the auditory pathway. They lack auditory-nerve responses to acoustic stimuli, although auditory brainstem responses could be elicited by electrical stimuli.|||Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, sodium and phosphate (PubMed:18215623, PubMed:18080752, PubMed:12384506). At the synaptic vesicle membrane, mainly functions as an uniporter that mediates the uptake of L-glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells (PubMed:18215623, PubMed:18080752, PubMed:12384506). The L-glutamate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (PubMed:12384506). In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification (By similarity). At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation (By similarity). The symporter activity is electrogenic (By similarity). Moreover, operates synergistically with SLC18A3/VACHT under a constant H(+) gradient, thereby allowing striatal vesicular acetylcholine uptake (PubMed:18278042).|||The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release.|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Arg1 ^@ http://purl.uniprot.org/uniprot/Q61176 ^@ Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the arginase family.|||Binds 2 manganese ions per subunit.|||By T helper 2 (Th2) cytokines such as IL-4, IL-13 and IL-10. In tumor-infiltrating dendritic cells by prostaglandin E2.|||Cytoplasm|||Cytoplasmic granule|||Expressed in macrophages (PubMed:7537672, PubMed:12193690, PubMed:19360123). Expressed in precursor and mature group 2 innate lymphoid cells (ILC2s) (PubMed:27043409). Expressed in lung tumor-associated myeloid cells (PubMed:15313928). Expressed in lung tumor-infiltrating dendritic cells (PubMed:19414774).|||Functions in L-arginine homeostasis in nonhepatic tissues characterized by the competition between nitric oxide synthase (NOS) and arginase for the available intracellular substrate arginine. Arginine metabolism is a critical regulator of innate and adaptive immune responses. Involved in an antimicrobial effector pathway in polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated from the phagolysosome and depletes arginine in the microenvironment leading to suppressed T cell and natural killer (NK) cell proliferation and cytokine secretion (By similarity). In group 2 innate lymphoid cells (ILC2s) promotes acute type 2 inflammation in the lung and is involved in optimal ILC2 proliferation but not survival (PubMed:27043409). Plays a role in the immune response of alternatively activated or M2 macrophages in processes such as wound healing and tissue regeneration, immune defense against multicellular pathogens and parasites, and immune suppression and allergic inflammation; the regulatory outcome seems to be organ specific (PubMed:7537672, PubMed:19360123, PubMed:20483789, PubMed:23552798, PubMed:23637937). In tumor-infiltrating dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) plays a role in suppression of T cell-mediated antitumor immunity (PubMed:19414774, PubMed:23248265).|||Homotrimer (By similarity). Interacts with CMTM6 (By similarity).|||Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys. http://togogenome.org/gene/10090:Galnt4 ^@ http://purl.uniprot.org/uniprot/O08832 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a highest activity toward EA2 peptide substrate and a much lower activity with EPO-T, Muc2, Muc1a, Muc1b.|||Golgi apparatus membrane|||Highly expressed in sublingual gland, stomach, colon, small intestine and cervix. Expressed at intermediate levels in kidney, ovary, lung and uterus. Weakly expressed in spleen, liver, heart and brain. Not expressed in submandibular and parotid glands, skeletal muscle and testis.|||The ricin B-type lectin domain directs the glycopeptide specificity. It is required in the glycopeptide specificity of enzyme activity but not for activity with naked peptide substrates, suggesting that it triggers the catalytic domain to act on GalNAc-glycopeptide substrates.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Cygb ^@ http://purl.uniprot.org/uniprot/Q546K1|||http://purl.uniprot.org/uniprot/Q9CX80 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the globin family.|||Cytoplasm|||May have a protective function during conditions of oxidative stress. May be involved in intracellular oxygen storage or transfer. http://togogenome.org/gene/10090:Cebpz ^@ http://purl.uniprot.org/uniprot/A0A0R4J046|||http://purl.uniprot.org/uniprot/P53569 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CBF/MAK21 family.|||Nucleus|||Stimulates transcription from the HSP70 promoter.|||Ubiquitous. http://togogenome.org/gene/10090:Or5m12 ^@ http://purl.uniprot.org/uniprot/A2ASU7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:1700019D03Rik ^@ http://purl.uniprot.org/uniprot/Q9CPS8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small membrane AKAP family.|||Binds to type I regulatory subunits of protein kinase A (PKA-RI) and may anchor/target them to the plasma membrane.|||Cell membrane|||Interacts with PKA type I regulatory subunits PRKAR1A and PRKAR1B. Also binds to type II regulatory subunits, but at a tenfold lower affinity (By similarity).|||May be palmitoylated at Cys-3.|||Widely expressed, with very low levels in spleen and liver. http://togogenome.org/gene/10090:Hdlbp ^@ http://purl.uniprot.org/uniprot/Q8VDJ3 ^@ Function|||Subcellular Location Annotation ^@ Appears to play a role in cell sterol metabolism. It may function to protect cells from over-accumulation of cholesterol (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Srp68 ^@ http://purl.uniprot.org/uniprot/Q8BMA6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SRP68 family.|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (By similarity). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER (By similarity). The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER (By similarity). Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently (By similarity). The SRP complex possibly participates in the elongation arrest function (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Heterodimer with SRP72 (By similarity). SRP68/SRP72 heterodimer formation is stabilized by the presence of 7SL RNA (By similarity). Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9 (By similarity). Within the SRP complex, interacts (via C-terminus) with SRP72 (via N-terminus) (By similarity).|||The N-terminus is required for RNA-binding.|||nucleolus http://togogenome.org/gene/10090:Dgcr8 ^@ http://purl.uniprot.org/uniprot/Q9EQM6 ^@ Cofactor|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 heme group per homodimer.|||Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis (PubMed:17259983). Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing (By similarity). Involved in the silencing of embryonic stem cell self-renewal (PubMed:17259983).|||Expressed in embryonic stem cells. During embryo development it is expressed in neuroepithelium of primary brain, limb bud, vessels, thymus, and around the palate.|||Monomer; in absence of heme (By similarity). Homodimer; the association with heme promotes its dimerization (By similarity). Component of the microprocessor complex, or pri-miRNA processing protein complex, which is composed of DROSHA and DGCR8 (PubMed:26255770). The microprocessor complex is a heterotrimer; each of the two DROSHA RNase III domains binds one DGCR8 (via C-terminal region) (By similarity). Interacts with ILF3, NCL and DROSHA (By similarity). Interacts with CPSF3 and ISY1; this interaction is in an RNA dependent manner (PubMed:26255770). Interacts with PUS10; interaction promotes pri-miRNAs processing (By similarity).|||Nucleus|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Fnta ^@ http://purl.uniprot.org/uniprot/Q541Z2|||http://purl.uniprot.org/uniprot/Q61239 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Activated by the AGRIN-induced phosphorylation which is mediated by MUSK.|||Belongs to the protein prenyltransferase subunit alpha family.|||Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation.|||Heterodimer of FNTA and FNTB (farnesyltransferase) (By similarity). Heterodimer of FNTA and PGGT1B (geranylgeranyltransferase) (By similarity).|||Phosphorylated. Phosphorylation is mediated by MUSK upon AGRIN stimulation and results in the activation of FNTA. http://togogenome.org/gene/10090:Chd1 ^@ http://purl.uniprot.org/uniprot/P40201 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (By similarity). Required for maintaining open chromatin and pluripotency in embryonic stem cells (PubMed:19587682). Is also associated with histone deacetylase (HDAC) activity (PubMed:12890497).|||Abundance is higher in cells representing early stages of the B-lymphoid lineage such as pre-B and B-cells, than in cells representing mature plasmacytes or other cell lineages such as fibroblasts.|||Belongs to the SNF2/RAD54 helicase family.|||Component of the SAGA complex (By similarity). Specifically interacts with methylated H3K4me2 and H3K4me3. Interacts with the FACT complex, the PAF complex and the U2 snRNP. Interacts directly with PAF1, SFA3A1, SFA3A2, SFA3A3, SNF2 and SSRP1 (By similarity). Interacts with BCLAF1, NCoR, SRP20 and SAFB.|||Cytoplasm|||Nucleus|||The 2 chromodomains are involved in the binding to the histone H3 methyllysine at position 4 (H3K4me3).|||The CHD1 helical C-terminal domain (CHCT) binds DNA and nucleosomes. http://togogenome.org/gene/10090:Tnks1bp1 ^@ http://purl.uniprot.org/uniprot/P58871 ^@ PTM|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by TNKS1.|||Binds to the ANK repeat domain of TNKS1 and TNKS2.|||Chromosome|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Mtdh ^@ http://purl.uniprot.org/uniprot/Q80WJ7 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance (By similarity).|||Endoplasmic reticulum membrane|||In the mammary gland, expressed at the apical surface of epithelial cells lining ducts, as well as in the mammary fat pad. Not detected in the spleen, kidney, lung, or skin; minute amounts seen in the liver. Expressed in Purkinje neurons in the early postnatal and adult cerebellum. Overexpressed in mammary tumors (at protein level).|||Interacts with BCCIP, CREBBP/CBP and RELA/p65.|||Nucleus membrane|||Was originally thought to be a type II membrane protein but this is inconsistent with the results of multiple phosphorylation studies because this topology would locate the phosphorylation sites in the lumen or extracellularly rather than in the cytoplasm.|||nucleolus|||perinuclear region|||tight junction http://togogenome.org/gene/10090:Ear14 ^@ http://purl.uniprot.org/uniprot/Q5GAN2 ^@ Similarity ^@ Belongs to the pancreatic ribonuclease family. http://togogenome.org/gene/10090:Atf7 ^@ http://purl.uniprot.org/uniprot/Q3TZR9|||http://purl.uniprot.org/uniprot/V9GXN6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family.|||Homodimer; binds DNA as homodimer. Heterodimer; heterodimerizes with other members of ATF family and with JUN family members.|||Nucleus|||Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation. In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes. Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation. In response to TNF-alpha, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening. http://togogenome.org/gene/10090:Snai1 ^@ http://purl.uniprot.org/uniprot/Q02085 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylation by PARP1 increases protein half-life and may be involved in TGFB-induced SNAI1 up-regulation.|||Belongs to the snail C2H2-type zinc-finger protein family.|||Cytoplasm|||Embryos die early in gestation, exhibiting defects in gastrulation and mesoderm formation. Recessive lethal mutation.|||Interacts with LOXL2 and LOXL3 (By similarity). Interacts with FBXL14 and GSK3B. Interacts with BTRC; interaction occurs when it is phosphorylated on the destruction motif. Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains). Interacts (via N-terminal region) with CSNK2A1. Interacts with EGR1 upon TPA induction. Interacts (via N-terminal region) with LATS2; the interaction is dependent on LATS2 kinase activity but independent of SNAI1 Thr-203 phosphorylation. Interacts (via zinc fingers) with KPNB1 and TNPO1; the interactions mediate nuclear import. Interacts (via zinc fingers) with KPNA1; the interaction disrupts the transport complex with KPNB1 and prevents nuclear import increasing SNAI1 degradation in the cytoplasm. Interacts (via zinc fingers) with KPNA2; the interaction, in combination with KPNB1, mediates nuclear import. Interacts with KPNA4; this interaction mediates nuclear import. May interact (via zinc fingers) with IPO7. Interacts (via zinc fingers) with PARP1; the interaction requires SNAI1 to be poly-ADP-ribosylated and non-phosphorylated (active) by GSK3B. Interacts (via SNAG domain) with KDM1A; the interaction is necessary for the down-regulation of dimethylated H3K4 mark and promoter activity of E-cadherin/CDH1, CDN7 and KRT8. Interacts with TP53/p53 and (via zinc fingers) with NOTCH1 (via intracellular domain); the interactions induce SNAI1 degradation via MDM2-mediated ubiquitination and inhibit SNAI1-induced cell invasion. Interacts with MDM2; the interaction promotes SNAI1 ubiquitination. Interacts (via zinc fingers) with CSNK1E. Interacts with PAK1.|||Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. The N-terminal SNAG domain competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (in vitro) (By similarity). During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription (PubMed:24239292). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (PubMed:24239292). Associates with EGR1 and SP1 to mediate 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3'. In addition, may also activate the CDKN2B promoter by itself.|||Nucleus|||O-GlcNAcylation at Ser-112 is enhanced in hyperglycaemic conditions, it opposes phosphorylation by GSK3B, and stabilizes the protein.|||Phosphorylated by GSK3B. Once phosphorylated, it becomes a target for BTRC ubiquitination. Phosphorylation by CSNK1E, probably at Ser-104, provides the priming site for the subsequent phosphorylation by GSK3B, probably at Ser-100 and Ser-96. Phosphorylation by PAK1 may modulate its transcriptional activity by promoting increased accumulation in the nucleus. Phosphorylation at Ser-11 and Ser-104 positively regulates its function in induction of EMT and/or cell survival, respectively. Phosphorylation by LATS2, upon mitotic stress, oncogenic stress or Hippo pathway activation, occurs in the nucleus and promotes nuclear retention and stabilization of total cellular protein level.|||Postimplantation. Expression is observed in undifferentiated mesoderm and in tissues undergoing EMTs, namely the precursors of the neural crest cells and the primitive streak.|||Ubiquitinated on Lys-98, Lys-137 and Lys-146 by FBXL14 and BTRC leading to degradation. BTRC-triggered ubiquitination requires previous GSK3B-mediated SNAI1 phosphorylation. Ubiquitination induced upon interaction with NOTCH1 or p53 is mediated by MDM2. Ubiquitinated in a FBXL5-dependent manner; preventing interaction with DNA and promoting its degradation. Deubiquitinated by USP37; leading to stabilization.|||While expression is completely absent from non-invasive cell lines, it is high in invasive and metastatic cell types. http://togogenome.org/gene/10090:Dgki ^@ http://purl.uniprot.org/uniprot/D3YWQ0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic diacylglycerol kinase family.|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Has probably no preference for any of the diacylglycerols in terms of the acyl chain composition, especially for the acyl chain at the sn-2 position (By similarity). By controlling the diacylglycerol/DAG-mediated activation of RASGRP3, negatively regulates the Rap1 signaling pathway (PubMed:15894621). May play a role in presynaptic diacylglycerol/DAG signaling and control neurotransmitter release during metabotropic glutamate receptor-dependent long-term depression (PubMed:21119615).|||Homozygous knockout mice lacking Dgki do not display overt phenotype (PubMed:15894621). They are slower to habituation to a novel environment, but have normal levels of locomotor activity, anxiety, and motor coordination (PubMed:21119615). They display a small increase in presynaptic release probability and synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (PubMed:21119615).|||In brain, expressed in the hippocampus and cerebellum with stronger expression in the Purkinje cell layer (at protein level) (PubMed:21119615). Expressed in kidney (PubMed:15894621).|||Interacts (via PDZ-binding motif) with DLG4; controls the localization of DGKI to the synapse (By similarity). Interacts (via PDZ-binding motif) with DLG1 (By similarity). Interacts (via PDZ-binding motif) with DLG2 (By similarity). Interacts (via PDZ-binding motif) with DLG3 (PubMed:21119615). May interact with RASGRP3; involved in the regulation of RASGRP3 activity (Probable).|||Nucleus|||Postsynapse|||Postsynaptic density|||Presynapse|||Synaptic cell membrane|||axon|||cytosol|||dendrite|||synaptic vesicle membrane http://togogenome.org/gene/10090:Zxdb ^@ http://purl.uniprot.org/uniprot/A2CE44 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZXD family.|||Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.|||Nucleus|||Self-associates. Interacts with ZXDC and CIITA (By similarity). http://togogenome.org/gene/10090:Or1af1 ^@ http://purl.uniprot.org/uniprot/Q7TRY4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sox14 ^@ http://purl.uniprot.org/uniprot/Q04892|||http://purl.uniprot.org/uniprot/Q3UUP3|||http://purl.uniprot.org/uniprot/Q497H4|||http://purl.uniprot.org/uniprot/Q7TNS9 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a negative regulator of transcription.|||Highly expressed in developing brain and spinal cord.|||Nucleus http://togogenome.org/gene/10090:Dynll2 ^@ http://purl.uniprot.org/uniprot/Q9D0M5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures (By similarity).|||Belongs to the dynein light chain family.|||Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits which present intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. Dynein ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer (PubMed:11546872). Interacts with DYNC1I1 (PubMed:11148209). Interacts with BMF (PubMed:11546872). Component of the myosin V motor complex (PubMed:11546872). Interacts with BCAS1 (By similarity). Interacts with Basson/BSN (By similarity). Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton (By similarity). Interacts with IQUB (PubMed:36417862).|||cytoskeleton http://togogenome.org/gene/10090:Tmem222 ^@ http://purl.uniprot.org/uniprot/Q8BVA2 ^@ Subcellular Location Annotation ^@ Membrane|||dendrite http://togogenome.org/gene/10090:Dner ^@ http://purl.uniprot.org/uniprot/Q8JZM4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expression in the central nervous system starts at 11 dpc, peaks during postnatal development and declines in the adult brain. At P7 and P20, present in several types of post-mitotic neurons, including cortical and hippocampal pyramidal neurons, cerebellar granule cells and Purkinje cells. Absent from mitotic neuroblasts in the ventricular zones.|||Interacts with AP1G1. Interacts with NOTCH1.|||Mediates neuron-glia interaction during astrocytogenesis. May promote differentiation of Bergmann glia during cerebellar development by activating DELTEX-dependent NOTCH1 signaling.|||Mice show no obvious abnormality and no apparent survival disadvantage. However, they have delayed cerebellar histogenesis and exhibit motor discoordination at adult stages.|||N-glycosylated.|||Specifically expressed in brain neurons (at protein level). http://togogenome.org/gene/10090:Cmtm6 ^@ http://purl.uniprot.org/uniprot/Q9CZ69 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chemokine-like factor family.|||Cell membrane|||Early endosome membrane|||Interacts with PD-L1/CD274 (via transmembrane domain); the interaction is direct. Interacts with CMTM4. Interacts with CD58, ARG1, ENO1 and TMPO.|||Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Associates with both constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where it protects PD-L1/CD274 from being targeted for lysosomal degradation, likely by preventing its ubiquitination. May stabilize PD-L1/CD274 expression on antigen presenting cells and potentiates inhibitory signaling by PDCD1/CD279, its receptor on T-cells, ultimately triggering T-cell anergy.|||Recycling endosome membrane http://togogenome.org/gene/10090:Ptges3l ^@ http://purl.uniprot.org/uniprot/Q9D9A7 ^@ Similarity ^@ Belongs to the p23/wos2 family. http://togogenome.org/gene/10090:Ccr9 ^@ http://purl.uniprot.org/uniprot/Q9WUT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Highly expressed in the thymus and low in lymph nodes and spleen.|||Receptor for chemokine SCYA25/TECK. Subsequently transduces a signal by increasing the intracellular calcium ions level. http://togogenome.org/gene/10090:Sowaha ^@ http://purl.uniprot.org/uniprot/Q8BLS7 ^@ Similarity ^@ Belongs to the SOWAH family. http://togogenome.org/gene/10090:Gramd4 ^@ http://purl.uniprot.org/uniprot/Q8CB44 ^@ Caution|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with RTN4 (isoform B).|||It is uncertain whether Met-1 or Met-52 is the initiator.|||Mitochondrion membrane|||Plays a role as a mediator of E2F1-induced apoptosis in the absence of p53/TP53 (By similarity). Inhibits TLR9 response to nucelic acids and regulates TLR9-mediated innate immune response (PubMed:25917084).|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:Pcdha5 ^@ http://purl.uniprot.org/uniprot/Q91Y15 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Galr3 ^@ http://purl.uniprot.org/uniprot/O88853 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for the hormone galanin and spexin-1. http://togogenome.org/gene/10090:Prl7b1 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0K6|||http://purl.uniprot.org/uniprot/Q8CGZ9 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Detectable throughout the second half of gestation.|||Expression restricted to placenta. Abundantly expressed in trophoblast cells of the junctional zone and trophoblasts migrating into the mesometrial decidua.|||Secreted http://togogenome.org/gene/10090:Tuba8 ^@ http://purl.uniprot.org/uniprot/Q9JJZ2 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At embryonic day (E) 13.5, expressed in the cortical preplate and cingulate cortex. By 15.5 dpc, the strongest expression is seen in the cortical plate. By 18.5 dpc, cortical expression is most intense in the upper layers and subplate. There is strong expression in the areas CA1-3 of the hippocampus. At P0, cortical expression is strongest in the dense cortical plate and subplate. Hippocampal expression is more intense in areas CA1-3 than in the dentate gyrus. At P8, lamination is almost complete and cortical expression is strongest in layers II-III and V and the subplate. There is also expression in the mediodorsal nuclei of the thalamus, the mitral cell layer of the olfactory bulb, and the external granular layer, molecular layer, and internal granular cell layer of the cerebellum.|||Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Expressed at highest levels in the testis, followed by skeletal and heart muscle. Expressed at low levels in the developing brain.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The C-terminal phenylalanine residue is cleaved by KIAA0895L/MATCAP.|||The MREC motif may be critical for tubulin autoregulation.|||This tubulin does not have a C-terminal tyrosine; however, its C-terminal phenylalanine residue can be cleaved.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Cdcp3 ^@ http://purl.uniprot.org/uniprot/Q8BZE1 ^@ Similarity ^@ Belongs to the DMBT1 family. http://togogenome.org/gene/10090:Sdcbp2 ^@ http://purl.uniprot.org/uniprot/Q99JZ0 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds phosphatidylinositol 4,5-bisphosphate (PIP2). May play a role in the organization of nuclear PIP2, cell division and cell survival.|||Cell membrane|||Cytoplasm|||Monomer and homodimer. Interacts with SDCBP. Interacts with TM4SF1.|||Nucleus speckle|||The two PDZ domains mediate the interaction with phosphatidylinositol 4,5-bisphosphate (PIP2) and target SDCBP2 to the plasma membranes and nucleoli, PIP2-rich regions.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Tifab ^@ http://purl.uniprot.org/uniprot/Q8JZM6 ^@ Function|||Subunit|||Tissue Specificity ^@ Expressed at high levels in spleen and at moderate levels in lung, thymus, and small intestine.|||Inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA.|||Interacts with TIFA. http://togogenome.org/gene/10090:H1f6 ^@ http://purl.uniprot.org/uniprot/I7HFT9|||http://purl.uniprot.org/uniprot/Q07133 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the histone H1/H5 family.|||Chromosome|||Citrullination at Arg-56 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.|||Nucleus|||Phosphorylated in early spermatids.|||Testis-specific histone H1 that forms less compacted chromatin compared to other H1 histone subtypes. Formation of more relaxed chromatin may be required to promote chromatin architecture required for proper chromosome regulation during meiosis, such as homologous recombination. Histones H1 act as linkers that bind to nucleosomes and compact polynucleosomes into a higher-order chromatin configuration.|||Testis-specific.|||This histone is a testis-specific H1 variant that appears during meiosis in spermatogenesis. http://togogenome.org/gene/10090:Rpn1 ^@ http://purl.uniprot.org/uniprot/Q5RKP4|||http://purl.uniprot.org/uniprot/Q8BMR3|||http://purl.uniprot.org/uniprot/Q91YQ5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OST1 family.|||Component of the oligosaccharyltransferase (OST) complex.|||Component of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity). Interacts with TMEM35A/NACHO (PubMed:32783947).|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Melanosome|||Membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity.|||Ufmylated by UFL1 in response to endoplasmic reticulum stress, promoting reticulophagy of endoplasmic reticulum sheets. http://togogenome.org/gene/10090:Tmem116 ^@ http://purl.uniprot.org/uniprot/G3X9M9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Txk ^@ http://purl.uniprot.org/uniprot/A0A0G2JG94|||http://purl.uniprot.org/uniprot/B2RQ20|||http://purl.uniprot.org/uniprot/P42682 ^@ Activity Regulation|||Caution|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation by FYN.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.|||Cell membrane|||Cytoplasm|||Expressed in early thymocytes, T-cells and mast cells.|||Interacts with PARP1 and EEF1A1 (By similarity). Interacts with SH2D2A (PubMed:10587356). Interacts with FYN (PubMed:11353545).|||Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation leads to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with PARP1 and EEF1A1 (By similarity). Within the complex, phosphorylates both PARP1 and EEF1A1 (By similarity). Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.|||Nucleus|||Phosphorylated at Tyr-420 by FYN. Autophosphorylation at Tyr-91 is critical for the activation of TXK, leading to the up-regulation of IFN-gamma gene transcription.|||Produced by alternative initiation at Met-55 of isoform 1.|||The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location.|||Unlike the other TEC subfamily members, TXK is activated independently of the activity of phosphatidylinositol 3-kinase, consistent with its lack of a PH domain. Membrane association is performed through palmitoylation at the N-terminus. http://togogenome.org/gene/10090:Bpifb9a ^@ http://purl.uniprot.org/uniprot/Q80XI7 ^@ Miscellaneous|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in lung. Not detected in other tissues tested (at protein level).|||May be due to intron retention.|||N-glycosylated. The N-glycans consist mainly of complex sialylated and fucosylated biantennary structures.|||Secreted http://togogenome.org/gene/10090:Card14 ^@ http://purl.uniprot.org/uniprot/Q99KF0 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ A linker region between the coiled-coil and PDZ region holds the protein in an inactive state.|||Acts as a scaffolding protein that can activate the inflammatory transcription factor NF-kappa-B and p38/JNK MAP kinase signaling pathways. Forms a signaling complex with BCL10 and MALT1, and activates MALT1 proteolytic activity and inflammatory gene expression. MALT1 is indispensable for CARD14-induced activation of NF-kappa-B and p38/JNK MAP kinases. May play a role in signaling mediated by TRAF2, TRAF3 and TRAF6 and protects cells against apoptosis.|||Cytoplasm|||Interacts (via CARD domain) with BCL10 (via CARD domain). Forms a complex with MALT1 and BCL10; resulting in the formation of a CBM (CARD14-BLC10-MALT1) complex. Interacts with TRAF2, TRAF3 and TRAF6.|||Supposed to contain a SH3 domain which is not detected by PROSITE, Pfam or SMART. http://togogenome.org/gene/10090:Oas1e ^@ http://purl.uniprot.org/uniprot/A0A0J9YV76|||http://purl.uniprot.org/uniprot/Q8C2W3 ^@ Similarity ^@ Belongs to the 2-5A synthase family. http://togogenome.org/gene/10090:Pcsk1 ^@ http://purl.uniprot.org/uniprot/P63239|||http://purl.uniprot.org/uniprot/Q32MU0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S8 family.|||Belongs to the peptidase S8 family. Furin subfamily.|||Increase in unprocessed AGRP.|||Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP.|||Vesicle|||secretory vesicle http://togogenome.org/gene/10090:Smurf2 ^@ http://purl.uniprot.org/uniprot/A2A5Z6 ^@ Activity Regulation|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activated by NDFIP1- and NDFIP2-binding.|||Auto-ubiquitinated and ubiquitinated in the presence of RNF11 and UBE2D1 (By similarity). Ubiquitinated by the SCF(FBXL15) complex and TTC3, leading to its degradation by the proteasome (By similarity). 'Lys-48'-linked polyubiquitination mediated by TRAF4 at Lys-119 leads to SMURF2 proteasomal degradation (By similarity).|||Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1. Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation. SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation. Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation.|||Interacts (via WW domains) with SMAD1. Interacts (via WW domains) with SMAD2 (via PY-motif). Interacts (via WW domains) with SMAD3 (via PY-motif). Interacts with SMAD6. Interacts with SMAD7 (via PY-motif) and TGFBR1; SMAD7 recruits SMURF2 to the TGF-beta receptor and regulates its degradation. Does not interact with SMAD4; SMAD4 lacks a PY-motif. Interacts with AIMP1 (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (By similarity). Interacts with TTC3 (By similarity).|||Level decreases under the suppression of SCYE1, suggesting that AIMP1 stabilizes SMURF2.|||Membrane raft|||Nucleus|||The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.|||The second and third WW domains are responsible for interaction with the PY-motif of R-SMAD (SMAD1, SMAD2 and SMAD3).|||Up-regulated about ten-fold by activation of the TNF-signaling pathway in vitro. http://togogenome.org/gene/10090:Pofut2 ^@ http://purl.uniprot.org/uniprot/B2RV73|||http://purl.uniprot.org/uniprot/Q8VHI3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 68 family.|||Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue in the consensus sequence C1-X-X-S/T-C2 of thrombospondin type I repeats (TSRs) where C1 and C2 are the first and second cysteines of the repeat, respectively (PubMed:20637190). O-fucosylates members of several protein families including the ADAMTS, the thrombospondin (TSP) and spondin families (PubMed:20637190). Required for the proper secretion of ADAMTS family members such as ADAMTSL1 and ADAMTS13 (By similarity). The O-fucosylation of TSRs is also required for restricting epithelial to mesenchymal transition (EMT), maintaining the correct patterning of mesoderm and localization of the definite endoderm (PubMed:20637190).|||Endoplasmic reticulum|||Golgi apparatus|||Null mice embryos die before 10.5 dpc. At the onset of gastrulation at 6.5 dpc, embryos are rounder and the embryonic and extra-embryonic ectoderm appears thickened and disorganized. Expression of NODAL and WNT3 is significantly expanded and/or displaced in the primitive streak as is BMP4 in the extra-embryonic ectoderm. By 7.5 dpc, embryos are unusually dense and shorter characterized by a dumb-bell appearance. There is unrestricted epithelial to mesenchymal transition (EMT) producing an abundance of mesenchymal cells. SNAIL1 expression is expanded and E-cadherin expression decreased. There is distal expansion of the proximal visceral endoderm. http://togogenome.org/gene/10090:Srebf2 ^@ http://purl.uniprot.org/uniprot/Q3U1N2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activation by cleavage is down-regulated upon activation of SIRT3-dependent PRKAA1/AMPK-alpha signaling cascade which leads to inhibition of ATP-consuming lipogenesis to restore cellular energy balance.|||Belongs to the SREBP family.|||COPII-coated vesicle membrane|||Death around embryonic day 7-8.|||Endoplasmic reticulum membrane|||Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane. Interacts (via C-terminal domain) with RNF139.|||Golgi apparatus membrane|||Homodimer; efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein (PubMed:11283257). Interacts with LMNA (PubMed:11929849).|||Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis (PubMed:9616204). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (By similarity). Regulates transcription of genes related to cholesterol synthesis pathway (PubMed:9616204).|||Nucleus|||Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression.|||Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 2), which is embedded in the endoplasmic reticulum membrane (By similarity). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis (PubMed:9616204, PubMed:16100574).|||Processed in the Golgi apparatus, releasing the protein from the membrane. At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum. In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases. The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane. Apoptosis triggers cleavage by the cysteine proteases caspase-3 and caspase-7. Cleavage and activation is induced by mediated cholesterol efflux.|||Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus. http://togogenome.org/gene/10090:Epdr1 ^@ http://purl.uniprot.org/uniprot/Q99M71 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ependymin family.|||Binds anionic lipids and gangliosides at acidic pH.|||Detected in brain, small intestine and in soleus, extensor digitorum longus and white gastrocnemius (at protein level) (PubMed:16954209). Detected in brain and skeletal muscle, and at lower leavels in heart (PubMed:11749721).|||Homodimer.|||Lysosome lumen|||N-glycosylated; the glycan contains mannose-6-phosphate moieties.|||Secreted http://togogenome.org/gene/10090:Adam10 ^@ http://purl.uniprot.org/uniprot/O35598|||http://purl.uniprot.org/uniprot/Q6NZC0 ^@ Activity Regulation|||Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Catalytically inactive when the propeptide is intact and associated with the mature enzyme (By similarity). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (By similarity).|||Cell membrane|||Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (By similarity). Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) at '687-Lys-|-Leu-688' (By similarity). Contributes to the normal cleavage of the cellular prion protein (By similarity). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (By similarity). Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (PubMed:9244301). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form (By similarity). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (PubMed:17245433). Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (PubMed:26876177). Enhances the cleavage of CHL1 by BACE1 (PubMed:29325091). Cleaves NRCAM (PubMed:29430990). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (By similarity). Involved in the development and maturation of glomerular and coronary vasculature (PubMed:30446855, PubMed:29397483). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (PubMed:30639848). May regulate the EFNA5-EPHA3 signaling (By similarity).|||Conditional knockout in endothelial cells results in abnormal myocardial compaction, insufficient systolic contraction, and enlarged hearts relative to body weight (PubMed:30446855). Conditional knockout in endothelial cells also results in dilated glomerular vessels and maturation defects in glomerular endothelial cells but kidney function is not impacted (PubMed:29397483).|||Cytoplasm|||Expressed in the brain, specifically in neurons and astrocytes (at protein level) (PubMed:23676497, PubMed:29325091). Expressed in inner and outer pillar cells of the organ of Corti (at protein level) (PubMed:30639848). Expressed in kidney and lung (PubMed:30463011).|||Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells (By similarity). Interacts with the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts (via extracellular domain) with TSPAN33 (via extracellular domain) and (via cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the docking of ADAM10 to zonula adherens through a PDZ11-dependent interaction between TSPAN33 and PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens (PubMed:30463011). Forms a ternary complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10 cleaves CADH1 which disrupts adherens junctions (PubMed:30639848). Interacts with EPHA2 (PubMed:10958785). Interacts with NGF in a divalent cation-dependent manner (By similarity). Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression (PubMed:23035126, PubMed:26668317). Interacts with TSPAN5, TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity (PubMed:23035126, PubMed:26668317). Interacts with DLG1; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (PubMed:23676497). Interacts (via extracellular domain) with BACE1 (via extracellular domain) (PubMed:29325091). Interacts with FAM171A1 (By similarity).|||Golgi apparatus membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins (By similarity). Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is sufficient for interaction with TSPAN15 (PubMed:26668317).|||The precursor is cleaved by furin and PCSK7.|||The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||Widely expressed in the nervous system at 18 dpc, with high expression in the posterior midbrain, which diminished toward the anterior midbrain.|||adherens junction|||axon|||clathrin-coated vesicle|||dendrite http://togogenome.org/gene/10090:Trir ^@ http://purl.uniprot.org/uniprot/Q9D735 ^@ Domain|||Function|||Subunit ^@ Exoribonuclease that is part of the telomerase RNA 3' end processing complex and which has the ability to all four unpaired RNA nucleotides from 5' end or 3' end with higher efficiency for purine bases (By similarity).|||Part of the telomerase RNA 3' end complex which contains about 488 proteins (By similarity).|||The C-terminus contains a key domain which is responsible for the RNA digestion activity (By similarity). http://togogenome.org/gene/10090:Slurp2 ^@ http://purl.uniprot.org/uniprot/P0DP59 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds and may modulate the functional properties of nicotinic and muscarinic acetylcholine receptors. May regulate keratinocytes proliferation, differentiation and apoptosis. In vitro moderately inhibits ACh-evoked currents of alpha-3:beta-2-containing nAChRs, strongly these of alpha-4:beta-2-containing nAChRs, modulates alpha-7-containing nAChRs, and inhibits nicotine-induced signaling probably implicating alpha-3:beta-4-containing nAChRs. Proposed to act on alpha-3:beta-2 and alpha-7 nAChRs in an orthosteric, and on mAChRs, such as CHRM1 and CHRM3, in an allosteric manner.|||Interacts with CHRNA3, CHRNA4, CHRNA5, CHRNA7, CHRNB2 and CHRNB4. Interacts with CHRM1 and CHRM3 probably in an allosteric manner (By similarity).|||Secreted|||Widely expressed, including in dendritic cells, macrophages, B- and T-lymphocytes. http://togogenome.org/gene/10090:Ercc6l ^@ http://purl.uniprot.org/uniprot/Q8BHK9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||Chromosome|||DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase. Functions as ATP-dependent DNA translocase. Can promote Holliday junction branch migration (in vitro).|||Expressed mainly in the neural tube and heart of 10.5 dpc embryo. Significantly down-regulated after alcohol exposure in embryonic brain and heart, but not in embryonic kidney, liver, or lung.|||Interacts with PLK1, which phosphorylates it. Both proteins are mutually dependent on each other for correct subcellular localization. Interacts (via N-terminal TPR repeat) with BEND3 (via BEN domains 1 and 3); the interaction is direct.|||Phosphorylation by PLK1 prevents the association with chromosome arms and restricts its localization to the kinetochore-centromere region.|||centromere|||kinetochore http://togogenome.org/gene/10090:Or56b34 ^@ http://purl.uniprot.org/uniprot/Q6W049 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Fnbp1l ^@ http://purl.uniprot.org/uniprot/E9PUI5|||http://purl.uniprot.org/uniprot/E9PUK3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FNBP1 family.|||Cell membrane|||Cytoplasmic vesicle|||Membrane|||Vesicle|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Chid1 ^@ http://purl.uniprot.org/uniprot/Q922Q9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 18 family.|||Interacts with STAB1.|||Lysosome|||Saccharide- and LPS-binding protein with possible roles in pathogen sensing and endotoxin neutralization. Ligand-binding specificity relates to the length of the oligosaccharides, with preference for chitotetraose (in vitro) (By similarity).|||Secreted http://togogenome.org/gene/10090:Or4c3 ^@ http://purl.uniprot.org/uniprot/Q9R0K2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc5a1 ^@ http://purl.uniprot.org/uniprot/Q8C3K6|||http://purl.uniprot.org/uniprot/Q8CCA7|||http://purl.uniprot.org/uniprot/Q9QXI6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Electrogenic Na(+)-coupled sugar simporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:22124465, PubMed:28974690). Has a primary role in the transport of dietary monosaccharides from enterocytes to blood. Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2. Additionally, functions as a D-glucose sensor in enteroendocrine cells, triggering the secretion of the incretins GCG and GIP that control food intake and energy homeostasis (PubMed:22124465). Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules (PubMed:22124465). Transports D-glucose into endometrial epithelial cells, controlling glycogen synthesis and nutritional support for the embryo as well as the decidual transformation of endometrium prior to conception (PubMed:28974690). Acts as a water channel enabling passive water transport in response to the osmotic gradient created upon sugar and Na(+) uptake. Has high water conductivity comparable to aquaporins and therefore is expected to play an important role in transepithelial water permeability, especially in the small intestine.|||Expressed in enterocytes and enteroendocrine cells of small intestine (at protein level) (PubMed:22124465). Expressed in S3 segments of renal proximal tubules (at protein level) (PubMed:22124465). Expressed in endometrial glandular and epithelial cells (at protein level) (PubMed:28974690).|||Membrane|||Mutant mice had significantly lower embryo implantation rate associated with lower litter size (PubMed:28974690). On a standard diet, they developed symptoms of the glucose and galactose malabsorption and died within 2 days after weaning, a phenotype reminiscent of GGM syndrome in humans (PubMed:22124465). Weaned mice survived and were fertile when maintained on a glucose and galactose free diet (PubMed:22124465).|||N-glycosylation is not necessary for the cotransporter function.|||The cholesterol-binding site is formed by transmembrane helices TM1, TM7 and TM13. http://togogenome.org/gene/10090:Eif2s3x ^@ http://purl.uniprot.org/uniprot/Q9Z0N1 ^@ Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.|||Encoded by an chromosome X-linked gene which escapes inactivation. Has a homolog on chromosome Y (Eif2s3y).|||Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). Along with its paralog on chromosome Y, may contribute to spermatogenesis up to the round spermatid stage (PubMed:26823431).|||Widely expressed. In the brain, high mRNA levels are observed in specific regions, including the habenula, anterodorsal thalamic nucleus, hippocampus, hypothalamus, and cerebellum. Also expressed in the embryonic brain. There is a differential expression between males and females, wich is tissue-specific. Females tend to have higher expression levels than males in the brain (cortex, hippocampus and paraventricular nucleus, but not in the habenula), as well as in other tissues. The up-regulation observed in females at the mRNA level may be due to the presence of 2 active copies of the gene.|||eIF2 is an heterotrimer composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (Eif2s3x and Eif2s3y) chain. eIF2 is member of the 43S pre-initiation complex (43S PIC). http://togogenome.org/gene/10090:Tcp11 ^@ http://purl.uniprot.org/uniprot/B2KF24|||http://purl.uniprot.org/uniprot/Q5FWA2 ^@ Similarity ^@ Belongs to the TCP11 family. http://togogenome.org/gene/10090:Dnajb4 ^@ http://purl.uniprot.org/uniprot/Q9D832 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Homodimer. The C-terminal section interacts with the C-terminal tail of OPRM1. Interacts also with SDIM1 (By similarity).|||Probable chaperone. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro). http://togogenome.org/gene/10090:Trpm7 ^@ http://purl.uniprot.org/uniprot/A2AI57|||http://purl.uniprot.org/uniprot/Q923J1 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Binds 1 zinc ion per subunit.|||Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium. Has a central role in magnesium ion homeostasis and in the regulation of anoxic neuronal cell death. Involved in TNF-induced necroptosis downstream of MLKL by mediating calcium influx. The kinase activity is essential for the channel function. May be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1).|||Forms heterodimers with TRPM6. Interacts with PLCB1 (By similarity). Homodimer.|||Found to be expressed in brain and skeletal muscle, with stronger signals in kidney, heart, liver and spleen.|||In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.|||In the N-terminal section; belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM7 sub-subfamily.|||Membrane http://togogenome.org/gene/10090:Pfn3 ^@ http://purl.uniprot.org/uniprot/Q9DAD6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the profilin family.|||Binds to actin and affects the structure of the cytoskeleton. Binds to poly-L-proline, phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 4-phosphate (PtdIns(4)P). Slightly reduces actin polymerization. May be involved in spermatogenesis.|||Interacts with ACTRT3.|||Nucleus|||Testis specific.|||cytoskeleton http://togogenome.org/gene/10090:Cyp2j9 ^@ http://purl.uniprot.org/uniprot/Q924D1 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Ano1 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQF2|||http://purl.uniprot.org/uniprot/G8JL82|||http://purl.uniprot.org/uniprot/Q8BHY3 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) (By similarity). Activated by heat with activation seen at temperatures above 44 degrees Celsius (PubMed:22634729). Activated by BDNF in radial glial cells (PubMed:31147466).|||Apical cell membrane|||Belongs to the anoctamin family.|||Calcium-activated chloride channel (CaCC) (PubMed:28561733, PubMed:29236691, PubMed:29236684, PubMed:25779870, PubMed:28963502, PubMed:22634729, PubMed:31147466, PubMed:34433575, PubMed:34089532, PubMed:24913262, PubMed:35135993, PubMed:23840801). Plays a role in transepithelial anion transport and smooth muscle contraction (PubMed:28561733, PubMed:29236691, PubMed:29236684). Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. Required for CFTR activation by enhancing endoplasmic reticulum Ca(2+) store release and is also required for CFTR membrane expression (By similarity). Required for basal and ATP-dependent mucus secretion in airways and intestine, probably by controlling exocytosis of mucus-filled granules by providing Ca(2+) to an apical signaling compartment (PubMed:30586313). Contributes to airway mucus expression induced by interleukins IL3 and IL8 and by the asthma-associated protein CLCA1 and is required for expression of mucin MUC5AC (By similarity). However, was shown in another study not to be required for MUC5AC expression (By similarity). Plays a role in the propagation of Ca(2+) waves in Kolliker's organ in the cochlea and contributes to the refinement of auditory brainstem circuitries prior to hearing onset (PubMed:35129434). In vomeronasal sensory neurons, modulates spontaneous firing patterns in the absence of stimuli as well as the firing pattern of pheromone-evoked activity (PubMed:34433575). Responsible for calcium-activated chloride channel activity in type I taste cells of the vallate papillae (PubMed:34089532). Acts as a heat sensor in nociceptive neurons (PubMed:22634729). In dorsal root ganglion neurons, plays a role in mediating non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-dependent itching, acting as a downstream effector of MRGPRs (PubMed:35135993). In the developing brain, required for the Ca(2+)-dependent process extension of radial glial cells (PubMed:31147466).|||Cell membrane|||Contains ten transmembrane regions, not eight as predicted.|||Expressed at the apical surface of the vomeronasal epithelium (at protein level) (PubMed:25779870, PubMed:34433575). Expressed in the lateral and septal nasal glands (at protein level) (PubMed:25779870). Highly expressed in pulmonary bronchiole epithelial cells, pancreatic and submandibular gland acinar cells, kidney proximal tubule, all retinal cell layers, most sensory cells of dorsal root ganglia, Leydig cells and spermatocytes (at protein level). In the dorsal root ganglia, detected in small-diameter nociceptive neurons and in larger myelinated neurons (at protein level) (PubMed:22634729). In the dorsal root ganglia, expressed in MrgprA3-positive neurons (at protein level) (PubMed:35135993). In the developing brain, highly expressed in the ventricular zone and subventricular zone at 12.5 dpc and 14.5 dpc where it is detected in radial glial cells but not in neurons with expression dramatically decreased at P1 (at protein level) (PubMed:31147466). Highly expressed in the endometrial stroma (at protein level) (PubMed:31175367). In taste buds of the vallate papillae, expressed in the apical region of type I taste cells (at protein level) (PubMed:34089532). In the kidney, expressed in the collecting duct (at protein level) (PubMed:24913262). In the retina, strongly expressed in the outer and inner plexiform layers, weakly expressed in some somata in the inner nuclear layer and ganglion cell layer and not expressed in the outer nuclear layer (at protein level) (PubMed:23840801). Expressed in various retinal neurons including rod bipolar cells (at protein level) (PubMed:23840801). Expressed in eye, brain, myometrium and endometrium with higher levels in endometrium than myometrium in estrus and day 18 pregnant mice (PubMed:31175367). Not detected in uterine smooth muscle cells (PubMed:31175367). Expressed at high levels in the thyroid gland and gastrointestinal muscles.|||Homodimer (PubMed:28561733, PubMed:29236691, PubMed:29236684). Interacts with CFTR (By similarity). Interacts with TRPV4 (PubMed:24509911).|||In the developing respiratory system, expressed in epithelium of trachea and lung at 12.5 dpc and 14.5 dpc but not detected in distal epithelial tips. Expressed in the mesenchyme adjacent to the proximal conducting airway epithelium at 14.5 dpc but not at 16.5 dpc. Epithelial expression persists at 16.5 dpc. At 18.5 dpc, high levels detected only in epithelial cells of terminal sacules. In the developing gastrointestinal tract, expressed in the esophageal mesenchyme and epithelium of posterior stomach and intestine. In the developing skeleton, expressed in the perichondria of the neural arch of developing vertebrae at 14.5 dpc and 16.5 dpc. In developing skin, expression is restricted to basal layers of the epidermis at 16.5 dpc.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mice display severe tracheomalacia with gaps in the tracheal cartilage rings along the entire length of the trachea (PubMed:18585372). 90% of mutants die within the first nine days of postnatal life and no mutants survive longer than 30 days postpartum (PubMed:18585372). Embryonic radial glial cells exhibit significantly shorter processes and mutant embryos display abnormal cortical organization and decreased cortical thickness (PubMed:31147466). Conditional knockout in mature vomeronasal sensory neurons abolishes calcium-activated chloride currents but does not affect Tmem16b expression or glomerular development in the accessory olfactory bulb (PubMed:25779870, PubMed:34433575). Conditional knockout in intestinal and respiratory epithelial cells abolishes both calcium-activated chloride channel activity and CFTR-dependent chloride secretion (PubMed:28963502). Conditional knockout in ciliated airway epithelial cells results in inhibition of basal airway mucus secretion with accumulation of mucus in airway club cells (PubMed:30586313). Conditional knockout in intestinal epithelial cells results in accumulation of mucus in both large and small intestinal goblet cells (PubMed:30586313). Conditional knockout in Syn1-expressing cells results in impaired social behavior, depressive-like behavior and decreased weight but does not affect locomotor activity, cognitive function or motor coordination (PubMed:29928889). Conditional knockout in dorsal root ganglion neurons results in reduction of heat-sensitive Cl- currents and a pronounced analgesic effect in response to heat (PubMed:22634729). Conditional knockout in dorsal root ganglion neurons results in reduced Mas-related G-protein coupled receptor-dependent itching (PubMed:35135993). Conditional knockout in the inner ear does not affect morphological development of the organ of Corti but impairs pre-hearing cochlear activity and spontaneous burst firing as well as sensitivity and frequency selectivity of sound-evoked firing of neurons of the medial nucleus of the trapezoid body (MNTB) (PubMed:35129434). Conditional knockout in smooth muscle cells does not alter Ca2+ signaling, uterine contraction, gestation length, or litter size (PubMed:31175367). RNAi-mediated knockdown reduces calcium-activated chloride currents and saliva production (PubMed:18724360). RNAi-mediated knockdown results in a pronounced analgesic effect in response to heat (PubMed:22634729).|||Presynapse|||The region spanning the fifth and sixth transmembrane domains probably forms the pore-forming region.|||The term 'anoctamin' was coined because these channels are anion selective and are predicted to have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Capn15 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLS3|||http://purl.uniprot.org/uniprot/Q9JLG8 ^@ Disruption Phenotype|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase C2 family.|||Highly expressed in the brain and eye during development (PubMed:32885237). Expressed in olfactory bulbs (at protein level) (PubMed:10708520).|||Knockout animals show significantly reduced viability. Homozygous knockout mice also weigh significantly less than their wild-type or heterozygous littermates. These mice also display severe developmental eye defects, including anophthalmia, microphthalmia, and cataract, and the presence of these phenotypes is significantly increased compared to wild-type or heterozygous mice. http://togogenome.org/gene/10090:Dao ^@ http://purl.uniprot.org/uniprot/A0A0R4J203|||http://purl.uniprot.org/uniprot/P18894|||http://purl.uniprot.org/uniprot/Q91WH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DAMOX/DASOX family.|||Homodimer.|||Peroxisome|||Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids. http://togogenome.org/gene/10090:Gfra3 ^@ http://purl.uniprot.org/uniprot/O35118 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GDNFR family.|||Cell membrane|||Interacts with SORL1.|||Receptor for the glial cell line-derived neurotrophic factor, artemin. Mediates the artemin-induced autophosphorylation and activation of the RET receptor tyrosine kinase (By similarity). http://togogenome.org/gene/10090:Iffo1 ^@ http://purl.uniprot.org/uniprot/Q8BXL9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intermediate filament family.|||Forms a heterotetramer with XRCC4 (By similarity). The interaction with XRCC4 is direct, involves LIG4-free XRCC4 and leads to relocalization of IFFO1 at the double-strand break (DSB) sites (By similarity). Interacts with LMNA; the interaction forms an interior nucleoskeleton and the recruitment to DNA double-strand breaks (By similarity).|||Nuclear matrix protein involved in the immobilization of broken DNA ends and the suppression of chromosome translocation during DNA double-strand breaks (DSBs) (PubMed:31548606). Interacts with the nuclear lamina component LMNA, resulting in the formation of a nucleoskeleton that will relocalize to the DSB sites in a XRCC4-dependent manner and promote the immobilization of the broken ends, thereby preventing chromosome translocation (PubMed:31548606). Acts as a scaffold that allows the DNA repair protein XRCC4 and LMNA to assemble into a complex at the DSB sites (PubMed:31548606).|||Nucleus|||Nucleus inner membrane|||Nucleus matrix|||nucleoplasm http://togogenome.org/gene/10090:Slco6c1 ^@ http://purl.uniprot.org/uniprot/Q8C0X7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353) (By similarity). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (Probable).|||flagellum membrane http://togogenome.org/gene/10090:Baz1b ^@ http://purl.uniprot.org/uniprot/Q9Z277 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (By similarity). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:16514417). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (By similarity). The WICH-5 ISWI chromatin remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (PubMed:16514417). Within the B-WICH complex has a role in RNA polymerase III transcription (By similarity). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (By similarity).|||Belongs to the WAL family. BAZ1B subfamily.|||Component of the WICH-1 ISWI chromatin remodeling complex, at least composed of SMARCA1 and BAZ1B/WSTF, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (By similarity). Within the WICH-1 ISWI chromatin remodeling complex interacts with SMARCA1; the interaction is direct (By similarity). Component of the WICH-5 ISWI chromatin remodeling complex (also called the WICH complex), at least composed of SMARCA5/SNF2H and BAZ1B/WSTF, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (PubMed:16514417). Within the WICH-5 ISWI chromatin remodeling complex interacts with SMARCA5/SNF2H; the interaction is direct (PubMed:16514417, PubMed:19092802). Component of the B-WICH chromatin remodeling complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (By similarity). Within the B-WICH chromatin remodeling complex, interacts with SMARCA5/SNF2H, DDX21, DEK, MYBBP1A, SF3B1 and ERCC6 (By similarity). Interacts with MYO1C (PubMed:16514417). Interacts with PCNA; the interaction is direct and is required for BAZ1B/WSTF binding to replication foci during S phase (By similarity). Interacts with CDT1 (By similarity).|||Expressed as early as day 7 and in equal amounts during gestation.|||Nucleus http://togogenome.org/gene/10090:Htr3b ^@ http://purl.uniprot.org/uniprot/Q9JHJ5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3B sub-subfamily.|||Cell membrane|||Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.|||Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.|||N-glycosylation is required for membrane localization.|||Postsynaptic cell membrane|||The HA-stretch region of HTR3B seems to confer increased conductance to HTR3A/HTR3B heteromers compared to that of HTR3A homomers. http://togogenome.org/gene/10090:Fbln1 ^@ http://purl.uniprot.org/uniprot/B2CQD6|||http://purl.uniprot.org/uniprot/Q08879|||http://purl.uniprot.org/uniprot/Q3TWK8 ^@ Caution|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibulin family.|||Detected in most organs (brain, heart, lung, spleen, liver and kidney). Neurons are the predominant source of production in the brain. Not expressed significantly by astrocytes or microglia.|||Glucocorticoids suppressed mRNA expression and protein synthesis.|||Homomultimerizes and interacts with various extracellular matrix components such as FN1, LAMA1, LMA2, NID, ACAN, CSPG2 and type IV collagen. Binding analysis demonstrated for isoform C a 100-fold stronger binding to the basement membrane protein NID than for isoform D. Interacts with FBLN7. Interacts with CCN3 (By similarity).|||Homomultimerizes and interacts with various extracellular matrix components.|||Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||The differential expression of the fibulin family contributes to the formation of molecularly distinct extracellular matrices already during early developmental stages of a large number of tissues. Increased expression at neonate stage in the brain. Expressed in interdigital regions of the handplate of a 12 dpc embryo and in the lateral perichondrial region. Similar expression persists in the 13 dpc handplate particularly in the perichondrial regions and apical aspects of the developing digits.|||extracellular matrix http://togogenome.org/gene/10090:Alpl ^@ http://purl.uniprot.org/uniprot/P09242|||http://purl.uniprot.org/uniprot/Q3TQ02 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (PubMed:10620060, PubMed:11028439, PubMed:14982838, PubMed:23942722, PubMed:33981039). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi), pyridoxal 5'-phosphate (PLP) and N-phosphocreatine are natural substrates (PubMed:19874193, PubMed:23942722, PubMed:33981039). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (PubMed:9056646, PubMed:10620060, PubMed:11004006, PubMed:11028439, PubMed:12082181, PubMed:14982838, PubMed:32035618). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (PubMed:20684022, PubMed:26457330). Also promotes dephosphorylation of osteopontin (SSP1), an inhibitor of hydroxyapatite crystallization in its phosphorylated state; it is however unclear whether ALPL/TNAP mediates SSP1 dephosphorylation via a direct or indirect manner (PubMed:23427088). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (PubMed:7550313). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (PubMed:19874193, PubMed:23942722, PubMed:23825434, PubMed:32028019). Also capable of dephosphorylating microbial products, such as lipopolysaccharides (LPS) as well as other phosphorylated small-molecules, such as poly-inosine:cytosine (poly I:C) (By similarity). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating hydrolysis of N-phosphocreatine to initiate a futile cycle of creatine dephosphorylation and phosphorylation (PubMed:33981039). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (PubMed:33981039).|||Belongs to the alkaline phosphatase family.|||Binds 1 Mg(2+) ion.|||Binds 2 Zn(2+) ions.|||By cold: up-regulated in response to cold both in brown and beige fat cells.|||Calcium-binding is structural and does not influence the alkaline phosphatase activity. At very high concentrations, calcium can however substitute for zinc at zinc-binding sites, leading to strongly reduced enzyme activity.|||Cell membrane|||Early death caused by defective metabolism of vitamin B6 (PubMed:7550313). At about two weeks of age, mice display seizures from which they die (PubMed:7550313, PubMed:9056646). Seizures are caused by a defect in the metabolism of pyridoxal 5'-phosphate (PLP) similar to that found in patients with hypophosphatasia, which ultimately results in a decrease in levels of 4-aminobutanoate (GABA) in the brain (PubMed:7550313). Mice do not show defects in skeletal formation during the first 8 days of life (PubMed:7550313, PubMed:10620060). Skeletal defects first appear at approximately 10 days of age and are characterized by worsening rachitic changes, osteopenia and fracture (PubMed:9056646, PubMed:10620060). Osteoblasts differentiate normally but are unable to initiate mineralization: histologic studies reveal developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones (PubMed:10620060, PubMed:11028439). Mineral crystals are initiated within matrix vesicles (MVs) of the growth plate and bone; however, mineral crystal proliferation and growth is inhibited in the matrix surrounding MVs, as in the case with hypophosphatasia (PubMed:14982838). Progressive osteoidosis from defective skeletal matrix mineralization is observed but not associated with features of secondary hyperparathyroidism (PubMed:10620060). Abnormal vitamin B6 metabolism is not the cause of impaired bone mineralization (PubMed:11169525). An accumulation of substrates is observed, characterized by strong elevation of urinary diphosphate (PPi) and phosphoethanolamine (PEA) levels and a striking accumulation of plasma PLP (PubMed:10620060). Mice lacking both Phospho1 and Alpl show a complete absence of skeletal mineralization, leading to perinatal lethality (PubMed:20684022). Bone mineralization in mice lacking both Enpp1 and Alpl is essentially normal, demonstrating that Enpp1 and Alpl are antagonist key regulators of bone mineralization by determining the normal steady-state levels of diphosphate (PPi) (PubMed:12082181). Conditional deletion in adipocytes leads to defective adaptive thermogenesis: defects are caused by abolition of the futile creatine cycle, thereby reducing whole-body energy expenditure and leading to rapid-onset obesity in mice, with no change in movement or feeding behavior (PubMed:33981039).|||Extracellular vesicle membrane|||Homodimer.|||In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP).|||Membrane|||Mitochondrion intermembrane space|||Mitochondrion membrane|||N-glycosylated.|||Not expressed prior to gastrulation in embryo, while it is expressed before in extraembryonic lineage cells destined to form the chorion (PubMed:7789278). Expressed in both embryonic and extraembryonic lineages during embryogenesis (PubMed:7789278). Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (PubMed:29148101).|||Phosphatase activity is specifically inhibited by 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425).|||Widely expressed (PubMed:3478679). Expressed in DRG neurons and spinal cord neurons (PubMed:23825434). http://togogenome.org/gene/10090:Scamp3 ^@ http://purl.uniprot.org/uniprot/E9Q855|||http://purl.uniprot.org/uniprot/O35609|||http://purl.uniprot.org/uniprot/Q3UXS0 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCAMP family.|||Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.|||Interacts with NEDD4 and NEDD4L and TSG101 (By similarity). Interacts with RNF126.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Monoubiquitinated. http://togogenome.org/gene/10090:Vrk1 ^@ http://purl.uniprot.org/uniprot/Q3UWH3|||http://purl.uniprot.org/uniprot/Q80X41 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Active in presence of Mn(2+), Mg(2+) and Zn(2+), but is not functional with Ca(2+) or Cu(2+). Has a higher affinity for Mn(2+) than for Mg(2+). RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3 (By similarity).|||Autophosphorylated at various serine and threonine residues (PubMed:14645249). Autophosphorylation does not impair its ability to phosphorylate p53/TP53 (By similarity). Phosphorylation by PLK3 leads to induction of Golgi fragmentation during mitosis (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.|||Cytoplasm|||Expressed from 10.5 dpc to 14 dpc in developing liver and then decreases. It increases again from 17.5 dpc and remains thereafter. Highly expressed in hematopoietic embryonic tissues from 10.5 dpc to 14.5 dpc. Weakly expressed in the yolk-sac.|||Highly expressed in testis. Expressed in liver, kidney and muscle. Weakly expressed in thymus, bone marrow and spleen.|||Nucleus|||Serine/threonine kinase involved in cell cycle, nuclear condensation and transcription regulation (PubMed:14645249, PubMed:9521809, PubMed:33076429). Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation (By similarity). Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2 (By similarity). Phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429). Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm (By similarity). Phosphorylates ATF2 which activates its transcriptional activity (By similarity). http://togogenome.org/gene/10090:Or2t47 ^@ http://purl.uniprot.org/uniprot/Q5NCD3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Serpina7 ^@ http://purl.uniprot.org/uniprot/Q3UEL9|||http://purl.uniprot.org/uniprot/Q8BII9 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Zfp532 ^@ http://purl.uniprot.org/uniprot/Q3TQ12|||http://purl.uniprot.org/uniprot/Q6NXK2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus http://togogenome.org/gene/10090:Or12k8 ^@ http://purl.uniprot.org/uniprot/Q8VF16 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cldn1 ^@ http://purl.uniprot.org/uniprot/O88551|||http://purl.uniprot.org/uniprot/Q4FJV3 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the claudin family.|||Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN3, but not CLDN2, homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with MPDZ and PATJ. Interacts with OCLN, CD81, CLDN4, CLDN6 and CLDN9 (By similarity).|||Cell membrane|||Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. Required for normal water homeostasis and to prevent excessive water loss through the skin, probably via an indirect effect on the expression levels of other proteins, since CLDN1 itself seems to be dispensable for water barrier formation in keratinocyte tight junctions.|||Complete perinatal lethality. Mice are born at the expected Mendelian rate, but die within one day after birth, due to severe defects in the skin barrier function, leading to rapid transepidermal water loss and dehydration.|||Detected in epidermis and liver (at protein level). Widely expressed, with highest levels in liver and kidney.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Ubr4 ^@ http://purl.uniprot.org/uniprot/A2AN08 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UBR4 family.|||Cytoplasm|||E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization. Regulates integrin-mediated signaling. May play a role in activation of FAK in response to cell-matrix interactions. Mediates ubiquitination of ACLY, leading to its subsequent degradation.|||Interacts with RB1 and calmodulin.|||Membrane|||Nucleus|||Widely expressed in adult and embryonic stages with highest levels in testis and brain.|||cytoskeleton http://togogenome.org/gene/10090:Zbtb4 ^@ http://purl.uniprot.org/uniprot/Q5F293 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expressed in adult and aged myogenic satellite cells.|||Interacts with HIPK2. Interacts with CBFA2T3. Interacts with ZBTB38.|||Not expressed during development, is induced during establishment of satellite cells and acquisition of quiescence.|||Nucleus|||Phosphorylated by HIPK2. This phosphorylation reduces stability and triggers ZBTB4 protein degradation in response to DNA damage.|||Transcriptional repressor with bimodal DNA-binding specificity. Represses transcription in a methyl-CpG-dependent manner. Binds with a higher affinity to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' but can also bind to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Can also bind specifically to a single methyl-CpG pair and can bind hemimethylated DNA but with a lower affinity compared to methylated DNA. Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (PubMed:27446912). http://togogenome.org/gene/10090:Esp1 ^@ http://purl.uniprot.org/uniprot/Q3LHH8 ^@ Developmental Stage|||Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the exocrine gland-secreted peptide family.|||Expressed at very low levels in most inbred strains with high levels detected only in strains BALB/c and DBA/2. Expressed at high levels in a number of wild mouse-derived strains.|||Expressed in the extraorbital lacrimal gland from where it is secreted into tears.|||Expression is observed after 4 weeks of age in males only. Not expressed in females or in males castrated at 3 weeks of age whereas expression is not down-regulated in castrated adult males.|||Male-specific phermone which is recognized by the Vmn2r116/V2rp5 receptor in the vomeronasal organ (VNO) and enhances female sexual receptive behavior (lordosis) upon male mounting, resulting in successful copulation.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Pqbp1 ^@ http://purl.uniprot.org/uniprot/Q91VJ5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic granule|||Detected in brain cortex and hippocampus neurons (at protein level). Expressed in brain with high level in cerebellar cortex, hippocampus and olfactory bulb.|||Except for the WW domain, the protein is intrinsically disordered.|||Interacts with POU3F2/Brn-2, ATXN1, TXNL4A, HTT and AR. Interaction with ATXN1 correlates positively with the length of the polyglutamine tract. Interacts with RNA polymerase II large subunit in a phosphorylation-dependent manner. Forms a ternary complex with ATXN1 mutant and phosphorylated RNA polymerase II. Interacts (via C-terminus) with TXNL4A and CD2BP2. Interacts (via WW domain) with ATN1 and SF3B1, and may interact with additional splice factors. Interacts (via WW domain) with WBP11; Leading to reduce interaction between PQBP1 and TXNL4A. Interacts with CAPRIN1. Interacts with DDX1. Interacts with SFPQ. Interacts with KHSRP.|||Intrinsically disordered protein that acts as a scaffold, and which is involved in different processes, such as pre-mRNA splicing, transcription regulation, innate immunity and neuron development (By similarity). Interacts with splicing-related factors via the intrinsically disordered region and regulates alternative splicing of target pre-mRNA species (PubMed:23512658). May suppress the ability of POU3F2 to transactivate the DRD1 gene in a POU3F2 dependent manner (By similarity). Can activate transcription directly or via association with the transcription machinery (By similarity). May be involved in ATXN1 mutant-induced cell death (By similarity). The interaction with ATXN1 mutant reduces levels of phosphorylated RNA polymerase II large subunit (By similarity). Involved in the assembly of cytoplasmic stress granule, possibly by participating in the transport of neuronal RNA granules (By similarity). Also acts as an innate immune sensor of infection by retroviruses, by detecting the presence of reverse-transcribed DNA in the cytosol (By similarity). Directly binds retroviral reverse-transcribed DNA in the cytosol and interacts with CGAS, leading to activate the cGAS-STING signaling pathway, triggering type-I interferon production (By similarity).|||Nucleus|||Nucleus speckle|||The WW domain may play a role as a transcriptional activator directly or via association with the transcription machinery. The WW domain mediates interaction with WBP11, ATN1, SF3B1 and the C-terminal domain of the RNA polymerase II large subunit. http://togogenome.org/gene/10090:Pter ^@ http://purl.uniprot.org/uniprot/Q60866 ^@ Cofactor|||Similarity|||Tissue Specificity ^@ Belongs to the metallo-dependent hydrolases superfamily. Phosphotriesterase family.|||Binds 2 divalent metal cations per subunit.|||Expressed in kidney and liver. http://togogenome.org/gene/10090:Rpl18 ^@ http://purl.uniprot.org/uniprot/A0A1B0GSF7|||http://purl.uniprot.org/uniprot/P35980|||http://purl.uniprot.org/uniprot/Q58EW0|||http://purl.uniprot.org/uniprot/Q642K1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL18 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||Rough endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Fam78a ^@ http://purl.uniprot.org/uniprot/Q8C552 ^@ Similarity ^@ Belongs to the FAM78 family. http://togogenome.org/gene/10090:Emsy ^@ http://purl.uniprot.org/uniprot/Q8BMB0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer (By similarity). Interacts with the transactivation domain of BRCA2 (PubMed:14651845). Interacts with CBX1 (via chromoshadow domain) (By similarity). Interacts with ZMYND11 (By similarity). Does not interact with CBX3 or CBX5 (By similarity). Component of a nuclear receptor-mediated transcription complex composed of at least ZNF335, CCAR2 and EMSY; the complex stimulates the transcription of nuclear receptor target genes such as SOX9 and HOXA1 (By similarity). Within the complex interacts with CCAR2 and ZNF335 (By similarity). Components of this complex may associate with components of a histone methylation complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (By similarity). Within this complex, interacts with ASH2L and RBBP5 (By similarity).|||Nucleus|||Regulator which is able to repress transcription, possibly via its interaction with a multiprotein chromatin remodeling complex that modifies the chromatin (By similarity). Its interaction with BRCA2 suggests that it may play a central role in the DNA repair function of BRCA2 (By similarity). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (By similarity). http://togogenome.org/gene/10090:Setmar ^@ http://purl.uniprot.org/uniprot/Q80UJ9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Chromosome|||Histone methyltransferase that methylates 'Lys-4' and 'Lys-36' of histone H3, 2 specific tags for epigenetic transcriptional activation. Specifically mediates dimethylation of H3 'Lys-36'.|||In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.|||Nucleus http://togogenome.org/gene/10090:Trp53bp2 ^@ http://purl.uniprot.org/uniprot/E9QJU8|||http://purl.uniprot.org/uniprot/Q8CG79 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ASPP family.|||Interacts with P53/TP53; the interaction promotes pro-apoptotic activity (By similarity). Interacts with BCL2 (By similarity). Interacts with protein phosphatase 1. Interacts with RELA NF-kappa-B subunit. This interaction probably prevents the activation of apoptosis, possibly by preventing its interaction with p53/TP53. Interacts with APC2 and APPBP1. Interacts with DDX42 (via the C-terminus); the interaction is not inhibited by TP53BP2 ubiquitination and is independent of p53/TP53 (By similarity).|||Nucleus|||Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions with proteins such as TP53 (By similarity). Regulates p53/TP53 by enhancing the DNA binding and transactivation function of p53/TP53 on the promoters of proapoptotic genes in vivo. Inhibits the ability of APPBP1 to conjugate NEDD8 to CUL1, and thereby decreases APPBP1 ability to induce apoptosis. Impedes cell cycle progression at G2/M. Its apoptosis-stimulating activity is inhibited by its interaction with DDX42 (By similarity).|||The ankyrin repeats and the SH3 domain are required for a specific interactions with p53/TP53.|||perinuclear region http://togogenome.org/gene/10090:Rap2b ^@ http://purl.uniprot.org/uniprot/P61226|||http://purl.uniprot.org/uniprot/Q6ZWR0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Ras family.|||Endosome membrane|||Interacts with PLCE1. Interacts with SGSM1, SGSM2 and SGSM3 (By similarity). The GTP-bound form of RAP2B interacts with RUNDC3A.|||Palmitoylated.|||Palmitoylated. Unlike RAP2A and RAP2C, palmitoylation of RAP2B is not required for association with recycling endosome membranes and activation of TNIK.|||Recycling endosome membrane|||Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form.|||Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. Involved in EGFR and CHRM3 signaling pathways through stimulation of PLCE1. May play a role in cytoskeletal rearrangements and regulate cell spreading through activation of the effector TNIK. May regulate membrane vesiculation in red blood cells.|||The effector domain mediates the interaction with RUNDC3A. http://togogenome.org/gene/10090:Spint2 ^@ http://purl.uniprot.org/uniprot/Q9WU03 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Inhibitor of HGFAC (By similarity). Also inhibits plasmin, and plasma and tissue kallikrein (By similarity). Inhibits serine protease activity of TMPRSS13 (By similarity). Inhibits serine protease activity of ST14/matriptase in vitro (By similarity).|||Interacts with TMPRSS13; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13.|||Isoform 2 is more predominantly expressed than isoform 1.|||This inhibitor contains two inhibitory domains. http://togogenome.org/gene/10090:Gm4846 ^@ http://purl.uniprot.org/uniprot/B2RWH8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Phlda2 ^@ http://purl.uniprot.org/uniprot/O08969 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PHLDA2 family.|||Cytoplasm|||Expressed at high levels in the very early conceptus limited to polar trophectoderm. Strongly expressed in the ectoplacental cone shortly after implantation at 5.5 dpc, and the high expression remains restricted to the extraembryonic tissues at later stages. By 10.5 dpc expression is restricted to the labyrinthine trophoblast and the endodermal component of the visceral yolk sac. Between 12.5 and 14.4 dpc expression in placenta decreases, due to a number of expressing cells. On day 12 of gestation, the abundant expressing cells are trophoblast at the chorionic plate, and clustered type II trophoblast deeper in the labyrinth. Less expressed by terminally differentiated trophoblast. As early as 14.5 dpc, becomes confined to a monolayer of cells at the chorionic plate and to rare cells in septa that protrude into the labyrinth (at protein level).|||Maternal Phlda2 allele is activated, while paternal Phlda2 is repressed due to genomic imprinting.|||Membrane|||Mice are viable, and show overgrowth of placentas with expansion of the spongiotrophoblast. These larger placentas do not confer a fetal growth advantage.|||Plays a role in regulating placenta growth. May act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids.|||Specifically expressed at high levels in extraembryonic tissues in the developing conceptus (at protein level). Expressed in placenta and yolc sac. Expressed at low levels in fetal liver and kidney.|||The PH domain binds phosphoinositides with a broad specificity. It may compete with the PH domain of some other proteins, thereby interfering with their binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity).|||The Phlda2 locus is imprinted. Loss of imprinting results in overexpression, leading to placental growth retardation phenotypes. http://togogenome.org/gene/10090:Rasgrf1 ^@ http://purl.uniprot.org/uniprot/P27671 ^@ Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Brain.|||Homooligomer and heterooligomer with RASGRF2. Interacts with USP8, thereby regulating its stability.|||Phosphorylated by PLK2, leading to ubiquitination and degradation by the proteasome.|||Phosphorylated by SRC and LCK. Phosphorylation by LCK increases its capacity to stimulate the GDP/GTP exchange on Ras, whereas its phosphorylation by SRC seems not to have an effect on stimulation activity (By similarity).|||Promotes the exchange of Ras-bound GDP by GTP.|||The DH (DBL-homology) domain mediates interaction with RASGRF2.|||Ubiquitinated and degraded following phosphorylation by PLK2. http://togogenome.org/gene/10090:Spaca3 ^@ http://purl.uniprot.org/uniprot/A0A077S9M6|||http://purl.uniprot.org/uniprot/Q9D9X8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the glycosyl hydrolase 22 family, Thr-128 and Asn-145 are present instead of the conserved Glu and Asp which are active site residues. It is therefore expected that this protein lacks hydrolase activity.|||Belongs to the glycosyl hydrolase 22 family.|||Interacts with ASTL.|||Secreted|||Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. It could be a potential receptor for the egg oligosaccharide residue N-acetylglucosamine, which is present in the extracellular matrix over the egg plasma membrane. The processed form has no detectable bacteriolytic activity in vitro (By similarity).|||The processed form is expressed in sperm (at protein level). Expressed strongly in testis and epididymis and weakly in pancreas.|||acrosome membrane http://togogenome.org/gene/10090:Paqr5 ^@ http://purl.uniprot.org/uniprot/Q9DCU0 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ADIPOR family.|||Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(i) mediated pathway. May be involved in oocyte maturation. http://togogenome.org/gene/10090:Khsrp ^@ http://purl.uniprot.org/uniprot/Q3U0V1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KHSRP family.|||Binds to the dendritic targeting element and may play a role in mRNA trafficking. Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs (By similarity).|||Cytoplasm|||Nucleus|||Part of a ternary complex containing FUBP2, PTBP1, PTBP2 and HNRPH1. Interacts with PARN. Interacts with PQBP1. http://togogenome.org/gene/10090:Tnp2 ^@ http://purl.uniprot.org/uniprot/P11378 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Appears in elongating/condensing spermatids when histones are still detectable (PubMed:15163613). Coexpressed with H2ab1 during late spermiogenesis (PubMed:28366643).|||Belongs to the nuclear transition protein 2 family.|||Chromosome|||Male mice lacking both Tnp1 and Tnp2 are completely infertile, but protamine alone are capable of histone eviction (PubMed:15163613, PubMed:15189834, PubMed:15083521). A significant proportion of Prm2 remains unprocessed (PubMed:15163613, PubMed:15189834, PubMed:15083521). Chromatin in mature spermatozoa shows defects in density (PubMed:15189834, PubMed:15083521).|||Nucleus|||Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals (PubMed:15163613, PubMed:15189834, PubMed:15083521, PubMed:28366643). In condensing spermatids, loaded onto the nucleosomes, where it promotes the recruitment and processing of protamines, which are responsible for histone eviction (PubMed:28366643). The histone H2AB1-H2BC1/TH2B dimer is required for loading of TNP2 onto chromatin (PubMed:28366643). http://togogenome.org/gene/10090:Popdc2 ^@ http://purl.uniprot.org/uniprot/Q6P3F7|||http://purl.uniprot.org/uniprot/Q9ES82 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the popeye family.|||Expressed in the developing and adult heart, with high expression levels in the sinus and atrioventricular nodes. Also expressed in the bladder and skeletal muscle.|||Expression was first detected at 7.5 dpc in the cardiac crescent. Expression was observed in the myocardial layer but not in the endocardium. Expression was homogeneous in all heart segments with the exception of the outflow tract. Between 9.5 dpc and 10.5 dpc expression was also observed in the trabeculated areas. In more advanced stages of myocardial differentiation, expression in the ventricle was largely restricted to the compact layer.|||Important for the maintenance of cardiac function. Plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding and, probably, by increasing cell surface expression of the potassium channel KCNK2 and enhancing current density.|||Knockout mice are deficient to adapt heart rate to physiological stress, this deficiency develops in older mice. They show severe sinus node dysfunction with long pauses and intercurrent periods of normal synus rhythm. The sinus node structure is abnormal with a loss of pacemaker tissue from the inferior part of the sinus node and a compact structure of the superior sinus node.|||Membrane|||sarcolemma http://togogenome.org/gene/10090:Rcvrn ^@ http://purl.uniprot.org/uniprot/P34057 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a calcium sensor and regulates phototransduction of cone and rod photoreceptor cells (By similarity). Modulates light sensitivity of cone photoreceptor in dark and dim conditions (PubMed:25673692). In response to high Ca(2+) levels induced by low light levels, prolongs RHO/rhodopsin activation in rod photoreceptor cells by binding to and inhibiting GRK1-mediated phosphorylation of RHO/rhodopsin (By similarity). Plays a role in scotopic vision/enhances vision in dim light by enhancing signal transfer between rod photoreceptors and rod bipolar cells (PubMed:15882641). Improves rod photoreceptor sensitivity in dim light and mediates response of rod photoreceptors to facilitate detection of change and motion in bright light (PubMed:29435986).|||At postnatal day 11 abundantly expressed in the retina outer plexiform layer, outer nuclear layer, and outer limiting membrane, with weak expression in the inner nuclear layer and inner plexiform layer (PubMed:28151698). At postnatal day 22 abundantly expressed in the retina inner nuclear layer, outer plexiform layer, outer nuclear layer, outer limiting membrane, outer segment, and inner segment (PubMed:28151698).|||Belongs to the recoverin family.|||EF-hand 2 and EF-hand 3 domains are the low-affinity and the high-affinity calcium binding sites, respectively. EF-hand 1 and EF-hand 4 domains do not bind calcium due to substitutions that disrupt their respective Ca(2+) binding loops. The cooperative binding of calcium to the EF-hand 2 domain following EF-hand 3 domain calcium binding requires myristoylation (By similarity). Calcium binding to the 2 EF-hand domains induces exposure of the myristoyl group through a protein conformation change, this process known as the calcium-myristoyl switch facilitates binding to photoreceptor cell membranes (By similarity).|||Expressed in rod photoreceptors in the retina (at protein level).|||Homodimer; disulfide-linked (By similarity). Homodimerization is caused by prolonged intense illumination (By similarity). May form a complex composed of RHO, GRK1 and RCVRN in a Ca(2+)-dependent manner; RCVRN prevents the interaction between GRK1 and RHO (By similarity). Interacts (via C-terminus) with GRK1 (via N-terminus); the interaction is Ca(2+)-dependent (By similarity).|||Knockout mice exhibit reduced scotopic vision acuity, however do not show rod photoreceptor degeneration (PubMed:15882641). Rod photoreceptors have a higher visual response threshold resulting in a 4-fold enhancement in sensitivity to low light intensity, with no change in pupil size (PubMed:15882641). Dark adapted rod photoreceptors have a reduced recovery time following stimulus, a reduced adaption time to background light and sustained photoreceptor signaling response following stimulus (PubMed:29435986). Rod photoreceptors have an increased sensitivity to stimulus in saturating background conditions (PubMed:29435986). Mice show a decrease in response, sensitivity and photoreceptor recovery to light stimulus in dark-adapted cone photoreceptors (PubMed:25673692). Rcvrn, Guca1a, and Guca1b triple knockout mice have a sustained photoreceptor signaling response following stimulus during light response in rod photoreceptors (PubMed:29435986).|||Oxidation on Cys-39 occurs in response to prolonged intense illumination and results in the formation of disulfide homodimers, and to a lesser extent disulfide-linked heterodimers.|||Perikaryon|||Photoreceptor inner segment|||Photoreceptor outer segment membrane|||The N-terminal glycine is linked to one of four different types of acyl groups. The most abundant is myristoleate (14:1), but 14:0, 14:2, and 12:0 acyl residues are also present (By similarity). The Ca(2+) induced exposure of the myristoyl group, known as the calcium-myristoyl switch, promotes RCVRN binding to the photoreceptor cell membranes only when intracellular Ca(2+) concentration is high (By similarity).|||photoreceptor outer segment http://togogenome.org/gene/10090:Or6c202 ^@ http://purl.uniprot.org/uniprot/Q8VFH6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chrna9 ^@ http://purl.uniprot.org/uniprot/G3X8Z7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Cacnb4 ^@ http://purl.uniprot.org/uniprot/A2ATZ8|||http://purl.uniprot.org/uniprot/Q3TYI5|||http://purl.uniprot.org/uniprot/Q8R0S4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the calcium channel beta subunit family.|||The L-type calcium channel is composed of four subunits: alpha-1, alpha-2, beta and gamma. Interacts with FASLG (By similarity). Interacts with CBARP (PubMed:24751537).|||The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting. http://togogenome.org/gene/10090:Micos10 ^@ http://purl.uniprot.org/uniprot/Q7TNS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MICOS complex subunit Mic10 family.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13 (By similarity). This complex was also known under the names MINOS or MitOS complex (By similarity). The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9 (By similarity). The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with IMMT/MIC60 and MICOS13/MIC13 (By similarity). Interacts with APOO/MIC23/MIC26 and APOOL/MIC27 (By similarity). Interacts with ARMC1 (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Vmn1r138 ^@ http://purl.uniprot.org/uniprot/D3YTY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fxyd4 ^@ http://purl.uniprot.org/uniprot/Q9D2W0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FXYD family.|||Membrane http://togogenome.org/gene/10090:Washc4 ^@ http://purl.uniprot.org/uniprot/Q3UMB9 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting.|||Belongs to the SWIP family.|||Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. The WASH core complex associates via WASHC2 with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex (By similarity).|||Contaminating sequence. Potential poly-A sequence.|||Early endosome http://togogenome.org/gene/10090:Pou6f1 ^@ http://purl.uniprot.org/uniprot/Q5U4D4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the POU transcription factor family.|||Nucleus http://togogenome.org/gene/10090:Atp6v1g2 ^@ http://purl.uniprot.org/uniprot/G5E923|||http://purl.uniprot.org/uniprot/Q54A87|||http://purl.uniprot.org/uniprot/Q9WTT4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase G subunit family.|||Melanosome|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR.|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Duox2 ^@ http://purl.uniprot.org/uniprot/A0A494BAW1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.|||In the N-terminal section; belongs to the peroxidase family.|||Membrane http://togogenome.org/gene/10090:Cyp19a1 ^@ http://purl.uniprot.org/uniprot/P28649|||http://purl.uniprot.org/uniprot/Q3ZAT3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively. Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid. Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen. Also displays 2-hydroxylase activity toward estrone. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Pramel4 ^@ http://purl.uniprot.org/uniprot/Q3ULC4 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Msi2 ^@ http://purl.uniprot.org/uniprot/Q3TE41|||http://purl.uniprot.org/uniprot/Q920Q6 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Musashi family.|||Cytoplasm|||Phosphorylated.|||RNA binding protein that regulates the expression of target mRNAs at the translation level. May play a role in the proliferation and maintenance of stem cells in the central nervous system.|||Ubiquitous. Expressed in proliferating neural precursor cells.|||Up-regulated in astrocytes after brain injury. http://togogenome.org/gene/10090:Osgepl1 ^@ http://purl.uniprot.org/uniprot/Q6PEB4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KAE1 / TsaD family.|||Binds 1 divalent metal cation per subunit.|||Mitochondrion|||Monomer.|||Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read codons beginning with adenine. Probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. Involved in mitochondrial genome maintenance. http://togogenome.org/gene/10090:Epha5 ^@ http://purl.uniprot.org/uniprot/E9PUQ0|||http://purl.uniprot.org/uniprot/Q60629 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts (via SAM domain) with SAMD5 (via SAM domain) (PubMed:29749928).|||Membrane|||Phosphorylated. Phosphorylation is stimulated by the ligand EFNA5. Dephosphorylation upon stimulation by glucose, inhibits EPHA5 forward signaling and results in insulin secretion.|||Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.|||Specifically expressed in the brain. Highly expressed in hippocampus, tenia tecta, indusium griseum and piriform cortex. The highest level of expression is found in the CA3 region of the hippocampus and the pyramidal cell layer of the piriform cortex. In addition, elevated levels of expression are also found in amygdala, medial septum, nucleus of the diagonal band, and in olfactory bulb. Expressed in pancreatic islet cells (at protein level). Expressed in myogenic progenitor cells (PubMed:27446912).|||Within the developing nervous system, the expression is very dynamic. At 16.5 dpc expressed predominantly in the primordial cortex of the telencephalon. Besides the midbrain it is also expressed in the hypothalamus, and the neurohypophysis. Non neuronal expression domains include the ectoderm of the branchial arches, the ectoderm and mesenchyme surrounding the dorsal root ganglia, the intervertebral disks, maxillary and mandibulary mesenchymal elements as well as the nasal mesenchyme and ectoderm. In myogenic progenitor cells, expressed at least as early as 11.5 dpc until adulthood (PubMed:27446912).|||axon|||dendrite http://togogenome.org/gene/10090:Ssbp3 ^@ http://purl.uniprot.org/uniprot/Q9D032 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcription regulation of the alpha 2(I) collagen gene where it binds to the single-stranded polypyrimidine sequences in the promoter region.|||Nucleus http://togogenome.org/gene/10090:Crybb1 ^@ http://purl.uniprot.org/uniprot/Q9WVJ5 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms.|||Specific cleavages in the N-terminal arm occur during lens maturation and give rise to truncated forms, leading to impaired oligomerization and protein insolubilization. The protease responsible for this partial degradation could be calpain II. http://togogenome.org/gene/10090:Ppp1r15a ^@ http://purl.uniprot.org/uniprot/B2RRL7|||http://purl.uniprot.org/uniprot/P17564 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) By infection with various viruses such as vesicular stomatitis virus (VSV).|||Belongs to the PPP1R15 family.|||Endoplasmic reticulum membrane|||Expressed strongly in spleen and lung, moderately in thymus and muscle, and weakly in brain.|||Expression starts at 8.5 dpc, and decreases to undetectable levels at 10.5 dpc and 11.5 dpc. Expression is strongly up-regulated at 12.5 dpc, decreases at 16.5 dpc and reappears at 18.5 dpc. At 12.5 dpc, ubiquitously expressed, with high levels in brain, spinal cord, tongue, lung and genital tubercle.|||Interacts with PPP1CA (PubMed:9023344, PubMed:11381086). Interacts with EIF2S1 (By similarity). Interacts with PCNA (PubMed:9371605). Interacts with LYN and KMT2A/MLL1 (PubMed:11517336). Interacts with PPP1R1A and SMARCB1. Interacts with SMAD7. Interacts with BAG1. Interacts with NOX4 (By similarity).|||Mice display abnormal erythrocytes and reduced hemoglobin content due to defects in hemoglobin synthesis.|||Mitochondrion outer membrane|||Phosphorylated at multiple Ser/Thr residues. Phosphorylated on tyrosine by LYN; which impairs its antiproliferative activity. Phosphorylation at Tyr-239 enhances proteasomal degradation, this position is dephosphorylated by PTPN2.|||Polyubiquitinated. Exhibits a rapid proteasomal degradation with a half-life under 1 hour, ubiquitination depends on endoplasmic reticulum association.|||Recruits the serine/threonine-protein phosphatase PPP1CA to prevents excessive phosphorylation of the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress (PubMed:11381086, PubMed:12824288). Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1 (By similarity). May promote apoptosis by inducing TP53 phosphorylation on 'Ser-15' (By similarity). Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux (By similarity). Acts also a viral restriction factor by attenuating vesicular stomatitis virus (VSV) replication (PubMed:17670836).|||Specifically produced in response to stress: in absence of stress, some upstream open reading frame (uORF) of this transcript is translated, thereby preventing its translation (PubMed:19131336). By IL6 and various endoplasmic stresses such as methyl methanesulfonate (PubMed:12606582, PubMed:12824288, PubMed:8139541). http://togogenome.org/gene/10090:Lrrc42 ^@ http://purl.uniprot.org/uniprot/Q8R2U7 ^@ Similarity ^@ Belongs to the LRRC42 family. http://togogenome.org/gene/10090:Or6c65 ^@ http://purl.uniprot.org/uniprot/Q8VGI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nae1 ^@ http://purl.uniprot.org/uniprot/E0CZE0|||http://purl.uniprot.org/uniprot/Q3UK27|||http://purl.uniprot.org/uniprot/Q8VBW6 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.|||Binding of TP53BP2 to the regulatory subunit NAE1 decreases neddylation activity.|||Cell membrane|||Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M. Binds APP and TP53BP2 (By similarity).|||Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M.|||Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation (By similarity). The covalent attachment of NEDD8 to target proteins is known as 'neddylation' and the process is involved in the regulation of cell growth, viability and development.|||Ubiquitinated by TRIP12, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Dpysl2 ^@ http://purl.uniprot.org/uniprot/O08553 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.|||Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or DPYSL5. Interacts through its C-terminus with the C-terminus of CYFIP1/SRA1. Interacts with HTR4. Interacts with CLN6. Interacts with MICALL1.|||Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.|||Membrane|||Phosphorylation by DYRK2 at Ser-522 is required for subsequent phosphorylation by GSK3B (By similarity). Phosphorylation at Thr-514 by GSK3B abolishes tubulin-binding leading to destabilization of microtubule assembly in axons and neurodegeneration.|||Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis.|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Pnma1 ^@ http://purl.uniprot.org/uniprot/Q8C1C8 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PNMA family.|||Predominantly expressed in testis. Very low levels in the brain, including in the piriform cortex, hippocampus and some subcortical nuclei.|||nucleolus http://togogenome.org/gene/10090:Rps15a ^@ http://purl.uniprot.org/uniprot/P62245|||http://purl.uniprot.org/uniprot/Q5M9M4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS8 family.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity). Required for proper erythropoiesis (By similarity).|||Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Shank3 ^@ http://purl.uniprot.org/uniprot/Q4ACU6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals deficient for isoforms 1-7 exhibit self-injourious repetitive grooming and deficits in social interaction. They show defects at striatal synapses and cortico-striatal circuits with an increase in striatal volume, dendritic length, and surface area and a decrease of spine density, length and thickness of PSD. They seem to have an altered molecular composition of postsynaptic machinery in the striatum (PubMed:21423165). In contrast, animals deficient for isoforms 1 and 2 exhibit a normal initiation of social interaction with a perturbed recognition of social novelty (PubMed:21423165). In PubMed:21558424, animals deficient for isoforms 1 and 2 show abnormal social behaviors, communication patterns, repetitive behaviors, learning and memory. In CA1 hippocampus, the synaptic plasticity is impaired with longer dendritic spines, decreased spine density and deficient long-term potentiation. The expression of specific synaptic scaffolding proteins and receptor subunits are altered. Animals deficient for isoforms 1-5 exhibit self-injourious repetitive grooming, brain-region-specific up-regulation of ionotropic glutamate receptors and increased levels of SHANK2 (PubMed:22699619). Animals deficient for predominant isoforms containing exon 21 exhibit motor-coordination deficits, hypersensitivity to heat, novelty avoidance, altered locomotor response to novelty and minimal social abnormalities. They show a decrease in NMDA-AMPA excitatory postsynaptic current ratio in hippocampal CA1, reduced long-term potentiation and deficits in hippocampus-dependent spatial learning and memory (PubMed:24259569).|||Belongs to the SHANK family.|||Cytoplasm|||In brain, highly expressed in striatum, thalamus, hippocampus and granule cells of the cerebellum.|||In isoform 1, the N-terminal region preceding the ANK repeats interacts with the 6 ANK repeats in an intramolecular manner, thereby restricting access to ligands, such as SHARPIN and SPTAN1.|||Isoform 3 is weakly expressed at 17 dpc but its expression increases after birth.|||Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation.|||May homomultimerize via its SAM domain. Interacts with BAIAP2, DBNL and SLC17A7/VGLUT1. Interacts with DLGAP1/GKAP, GRM1/MGLUR1, GRM5/MGLUR5 and LZTS3 C-termini via its PDZ domain. Interacts with ABI1, HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain. Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts (via PDZ domain) with the GRIA1 subunit of the AMPA receptor (via PDZ-binding motif). Interacts with WASF1 and CYFIP2; the interactions mediate the association of SHANK3 with the WAVE1 complex. Interacts with ARPC2; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex. Interacts (via ANK repeats) with SHARPIN and SPTAN1. Interacts (via PDZ domain) with ARHGAP44 (probably via PDZ-binding motif); the interaction takes place in dendritic spines and promotes GRIA1 exocytosis. Interacts with CAMK2A (By similarity). Interacts with DIP2A (PubMed:31600191).|||Postsynaptic density|||Produced by alternative promoter usage and alternative splicing.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 3.|||Produced by alternative splicing of isoform 6.|||Produced by alternative splicing of isoform 8.|||Synapse|||dendritic spine http://togogenome.org/gene/10090:Prl3b1 ^@ http://purl.uniprot.org/uniprot/P09586|||http://purl.uniprot.org/uniprot/Q5SZY3 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Placental lactogen I is expressed in mid-pregnancy, while placental lactogen II is expressed throughout the later half of pregnancy.|||Secreted http://togogenome.org/gene/10090:Cnpy4 ^@ http://purl.uniprot.org/uniprot/Q8BQ47 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the canopy family.|||Highly expressed in lung, spleen, thymus, and uterus. Moderately expressed in kidney, stomach and placenta. Weakly expressed in brain, heart, liver, small intestine, skeletal muscle and testis.|||Interacts with TLR4.|||Plays a role in the regulation of the cell surface expression of TLR4.|||Secreted http://togogenome.org/gene/10090:Ssh1 ^@ http://purl.uniprot.org/uniprot/F8WHT2|||http://purl.uniprot.org/uniprot/Q76I79 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||Cleavage furrow|||Expressed in brain, heart, kidney and thymus. Also expressed at lower levels in liver, skeletal muscle, small intestine and spleen.|||Interacts with the 14-3-3 proteins YWHAB, YWHAG, YWHAQ, and YWHAZ. Interaction with 14-3-3 proteins inhibits phosphatase activity and also blocks recruitment to lamellipodia and stimulation by actin (By similarity). Interacts with actin and this stimulates phosphatase activity. Interacts with LIMK1.|||Midbody|||Phosphorylated. Inhibitory phosphorylation by PAK4 promotes binding to YWHAZ. Phosphorylation at Ser-970 is decreased by stimuli which promote actin reorganization and lamellipodia formation. Can be dephosphorylated and activated by PPP3CA/calcineurin A. Phosphorylation decreases immediately prior to telophase (By similarity).|||Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein.|||Tyrosine phosphatase activity has not been demonstrated for this protein to date.|||Ubiquitously expressed in the embryo at 14.5 dpc.|||cytoskeleton http://togogenome.org/gene/10090:Armc2 ^@ http://purl.uniprot.org/uniprot/Q3URY6 ^@ Disruption Phenotype|||Function|||Miscellaneous ^@ Due to intron retention.|||Male mice are infertile, while female fertility is not affected (PubMed:30686508). Spermatozoa exhibit multiple morphologic abnormalities including short, thick, and/or coiled flagella, whereas sperm heads conserve an overall typical hooked shape (PubMed:30686508).|||Required for sperm flagellum axoneme organization and function (PubMed:30686508). Involved in axonemal central pair complex assembly and/or stability (PubMed:30686508). http://togogenome.org/gene/10090:Sat1 ^@ http://purl.uniprot.org/uniprot/P48026 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family.|||Enzyme which catalyzes the acetylation of polyamines (PubMed:18690703). Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine (By similarity). This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines (By similarity). Also involved in the regulation of polyamine transport out of cells (By similarity). Also acts on 1,3-diaminopropane and 1,5-diaminopentane (By similarity).|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Rpl24 ^@ http://purl.uniprot.org/uniprot/Q8BP67 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL24 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||Mono-ADP-ribosylation at Glu-4 by PARP16 inhibits polysome assembly and mRNA loading, thereby inhibiting protein translation. http://togogenome.org/gene/10090:Fyttd1 ^@ http://purl.uniprot.org/uniprot/Q91Z49 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UIF family.|||Interacts with DDX39B/UAP56 and NXF1; interaction with DDX39B/UAP56 and NXF1 are mutually exclusive. Interacts with SSRP1; required for its recruitment to mRNAs (By similarity). Interacts with CHTOP.|||Nucleus speckle|||Required for mRNA export from the nucleus to the cytoplasm. Acts as an adapter that uses the DDX39B/UAP56-NFX1 pathway to ensure efficient mRNA export and delivering to the nuclear pore. Associates with spliced and unspliced mRNAs simultaneously with ALYREF/THOC4 (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Plxnb1 ^@ http://purl.uniprot.org/uniprot/B2RWT9|||http://purl.uniprot.org/uniprot/Q8CJH3 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Detected in brain, heart, lung, liver, kidney, stomach, testis, uterus and placenta (PubMed:12559962). Expressed in neurons and glia in the developing hippocampus (PubMed:29981480).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Monomer, and heterodimer with PLXNB2 after proteolytic processing (By similarity). Binds RAC1 that has been activated by GTP binding (By similarity). Interaction with SEMA4D promotes binding of cytoplasmic ligands (By similarity). Interacts with RRAS, ARHGEF11, ARHGEF12, ERBB2, MET, MST1R, RND1, RHOD, NRP1 and NRP2 (By similarity). Interacts with PLXNA1 (PubMed:12559962).|||Phosphorylated on tyrosine residues by ERBB2 and MET upon SEMA4D binding.|||Proteolytic processing favors heterodimerization with PLXNB2 and SEMA4D binding.|||Receptor for SEMA4D (PubMed:19788569). Plays a role in GABAergic synapse development (PubMed:23699507, PubMed:29981480). Mediates SEMA4A- and SEMA4D-dependent inhibitory synapse development (PubMed:23699507, PubMed:29981480). Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton (By similarity). Plays a role in axon guidance, invasive growth and cell migration (By similarity). http://togogenome.org/gene/10090:Vmn2r22 ^@ http://purl.uniprot.org/uniprot/E9Q7S8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Fkbp11 ^@ http://purl.uniprot.org/uniprot/Q9D1M7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FKBP-type PPIase family.|||Interacts with IFITM5.|||Membrane|||PPIases accelerate the folding of proteins during protein synthesis. http://togogenome.org/gene/10090:Mcts1 ^@ http://purl.uniprot.org/uniprot/Q9DB27 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Anti-oncogene that plays a role in cell cycle regulation; decreases cell doubling time and anchorage-dependent growth; shortens the duration of G1 transit time and G1/S transition. When constitutively expressed, increases CDK4 and CDK6 kinases activity and CCND1/cyclin D1 protein level, as well as G1 cyclin/CDK complex formation. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role as translation enhancer; recruits the density-regulated protein/DENR and binds to the cap complex of the 5'-terminus of mRNAs, subsequently altering the mRNA translation profile; up-regulates protein levels of BCL2L2, TFDP1, MRE11, CCND1 and E2F1, while mRNA levels remains constant. Hyperactivates DNA damage signaling pathway; increased gamma-irradiation-induced phosphorylation of histone H2AX, and induces damage foci formation. Increases the overall number of chromosomal abnormalities such as larger chromosomes formation and multiple chromosomal fusions when overexpressed in gamma-irradiated cells. May play a role in promoting lymphoid tumor development: lymphoid cell lines overexpressing MCTS1 exhibit increased growth rates and display increased protection against apoptosis. May contribute to the pathogenesis and progression of breast cancer via promotion of angiogenesis through the decline of inhibitory THBS1/thrombospondin-1, and inhibition of apoptosis. Involved in the process of proteasome degradation to down-regulate Tumor suppressor p53/TP53 in breast cancer cell; Positively regulates phosphorylation of MAPK1 and MAPK3 (By similarity).|||Belongs to the MCTS1 family.|||Cytoplasm|||Interacts (via PUA domain) with DENR.|||Phosphorylation is critical for stabilization and promotion of cell proliferation.|||The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function. MCT1 N-terminal region is required to enhance translation possibly through interaction with other proteins (By similarity). http://togogenome.org/gene/10090:Endov ^@ http://purl.uniprot.org/uniprot/Q8C9A2 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the endonuclease V family.|||Cytoplasm|||Endoribonuclease that specifically cleaves inosine-containing RNAs: cleaves RNA at the second phosphodiester bond 3' to inosine. Active against both single-stranded and double-stranded RNAs. Has strong preference for single-stranded RNAs (ssRNAs) toward double-stranded RNAs (dsRNAs). Cleaves mRNAs and tRNAs containing inosine. Also able to cleave structure-specific dsRNA substrates containing the specific sites 5'-IIUI-3' and 5'-UIUU-3'. Inosine is present in a number of RNAs following editing; the function of inosine-specific endoribonuclease is still unclear: it could either play a regulatory role in edited RNAs, or be involved in antiviral response by removing the hyperedited long viral dsRNA genome that has undergone A-to-I editing. Binds branched DNA structures.|||Highest levels detected in liver with high levels also found in heart, kidney and testis. Expressed at low levels in brain.|||Monomer. Interacts with PABPC1; the interaction is RNA-dependent and stimulates ENDOV activity.|||Probable cloning artifact.|||Stress granule|||Was initially characterized as an endodeoxyribonuclease involved in DNA repair (PubMed:12853604). While it shows some weak endodeoxyribonuclease activity in vitro, such activity probably does not exist in vivo.|||nucleolus http://togogenome.org/gene/10090:Mpdz ^@ http://purl.uniprot.org/uniprot/B2RQR2|||http://purl.uniprot.org/uniprot/Q3TUR5|||http://purl.uniprot.org/uniprot/Q8VBX6 ^@ Developmental Stage|||Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Expressed at the outer limiting membrane of the retina at 3 months of age.|||In the brain, it is strongly expressed in the choroid plexus. Within the hippocampal formation, strongest expression was seen in the soma of CA1-4 pyramidal cells. Expressed in most neocortical regions with the strongest expression in piriform cortex and amygdaloid nuclei but also detected in the subiculum and olfactory bulb. In the cerebellum, the highest level of expression was found in Purkinje cells. Moderately expressed in the granular layer and molecular layer. Expressed in the pontine nuclei, parts of spinal trigeminal nuclei, and the principal sensory trigeminal nuclei of the metencephalon. Expressed in all thalamic and hypothalamic nuclei, and the substantia nigra (at protein level). Ubiquitously expressed.|||Interacts with CLDN5, DLG4, GRIN1, SYNGAP1, CAMK2A and CAMK2B, HTR2A, HTR2B, HTR2C, PLEKHA1/TAPP1 and PLEKHA2/TAPP2 (By similarity). Interacts with F11R/JAM, CLDN1, NG2, CXADR, CRB1, MPP4 and PALS1. Interacts with FAT4 (via cytoplasmic domain). Interacts with DLL1 (PubMed:15509766).|||Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses (By similarity). Promotes clustering of HT2RC at the cell surface (By similarity).|||Postsynaptic density|||Probable cloning artifact.|||Synapse|||The PDZ domain 2 mainly binds CAMK2A and CAMK2B. The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 10 binds the C-terminal PDZ-binding motif of HTR2C. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds SYNGAP1 (By similarity). The PDZ domain 1 binds NG2. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT. The PDZ domain 13 binds CXADR.|||dendrite|||synaptosome|||tight junction http://togogenome.org/gene/10090:Slc4a8 ^@ http://purl.uniprot.org/uniprot/Q8JZR6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Expressed in the hippocampal neurons (at protein level). Highly expressed in brain with lower levels in lung, kidney and heart. In the kidney, there is high expression in the inner medulla, localized to the inner medullary collecting duct. In the brain, there seems to be three transcripts each having a different expression pattern. The smaller 3kb transcript has highest expression levels in the thalamus and the largest 9.5kb transcript has highest levels in the substantia nigra. The middle transcript of 4.4kb, which is also the main transcript in kidney, is highly expressed in thalamus. Hence, the highest levels are observed in the thalamus, amygdala and caudate nucleus and very low expression was seen in the corpus callosum.|||Homodimer.|||Mediates electroneutral sodium- and carbonate-dependent chloride-HCO3(-) exchange with a Na(+):HCO3(-) stoichiometry of 2:1 (PubMed:20389022). Plays a major role in pH regulation in neurons (PubMed:21593314). Mediates sodium reabsorption in the renal cortical collecting ducts (PubMed:20389022).|||synaptic vesicle membrane http://togogenome.org/gene/10090:Cldn2 ^@ http://purl.uniprot.org/uniprot/O88552 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Both female and male Cldn2-knockout mice are similarly hypercalciuric compared to wild-type littermates. Cldn2-null mice are hypercalciuric due to a primary defect in renal tubule calcium transport and develop papillary nephrocalcinosis. Cldn2-null mice are also found to have increased net intestinal calcium absorption, but reduced paracellular calcium permeability in the colon, suggesting reduced intestinal calcium secretion.|||By CDX1 and CDX2. Induction by CDX2, but not CDX1, is potentiated by TCF1.|||Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN3, but not CLDN1, homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.|||Cell membrane|||Expressed in the kidney, liver and intestine, with higher levels in the ileum than in the jejunum. Low levels in the brain.|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||The disulfide bond is necessary for pore formation, but is not required for correct protein trafficking.|||tight junction http://togogenome.org/gene/10090:Txlna ^@ http://purl.uniprot.org/uniprot/Q3UD58|||http://purl.uniprot.org/uniprot/Q6PAM1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the taxilin family.|||Binds to the C-terminal coiled coil region of syntaxin family members STX1A, STX3A and STX4A, but not when these proteins are complexed with SNAP25, VAMP2 or STXBP1, suggesting that it interacts with syntaxins that do not form the SNARE complex.|||May be involved in intracellular vesicle traffic and potentially in calcium-dependent exocytosis in neuroendocrine cells. http://togogenome.org/gene/10090:Osgep ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Y3|||http://purl.uniprot.org/uniprot/Q3UQ67|||http://purl.uniprot.org/uniprot/Q8BWU5 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the KAE1 / TsaD family.|||Binds 1 divalent metal cation per subunit.|||Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.|||Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. OSGEP likely plays a direct catalytic role in this reaction, but requires other protein(s) of the complex to fulfill this activity.|||Cytoplasm|||Mouse embryos display primary microcephaly characterized by significantly shorter cortex lengths, cortex-midbrain midline lengths and cortex widths. Mice do not show a renal phenotype.|||Nucleus|||Weakly expressed in 7, 11 and 17 day embryos. Expressed at a higher level in 15 day embryos.|||Widely expressed at low level. Expressed at intermediate level in lung. Weakly expressed in testis, skeletal muscle, kidney, liver, spleen, brain and heart. http://togogenome.org/gene/10090:Klk11 ^@ http://purl.uniprot.org/uniprot/Q9QYN3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Expressed in brain and prostate (isoform 1) and prostate (isoform 2).|||Possible multifunctional protease. Efficiently cleaves 'bz-Phe-Arg-4-methylcoumaryl-7-amide', a kallikrein substrate, and weakly cleaves other substrates for kallikrein and trypsin (By similarity).|||Secreted http://togogenome.org/gene/10090:St7 ^@ http://purl.uniprot.org/uniprot/Q99M95|||http://purl.uniprot.org/uniprot/Q99M96 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ST7 family.|||Membrane http://togogenome.org/gene/10090:Myl6b ^@ http://purl.uniprot.org/uniprot/Q8CI43 ^@ Function|||Subunit ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains.|||Regulatory light chain of myosin. Does not bind calcium. http://togogenome.org/gene/10090:Ddx43 ^@ http://purl.uniprot.org/uniprot/D3Z6P9 ^@ Similarity ^@ Belongs to the DEAD box helicase family. http://togogenome.org/gene/10090:Coa8 ^@ http://purl.uniprot.org/uniprot/Q9CQW7 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the COA8 family.|||Expressed in atherosclerotic smooth muscle cells (at protein level). Expressed in aorta, brain, heart, kidney, liver, lung and spleen. Isoform 1 is strongly expressed in Kidney. Isoform 2 is strongly expressed in brain.|||First thought to play a role in the regulation of apoptosis, mediating mitochondria-induced cell death in vascular smooth muscle cells through the release of cytochrome c (COX) from mitochondria and the activation of the caspase cascade (PubMed:16782708, PubMed:18977203). However, recent studies show that it is not directly involved in apoptosis regulation but in the protection of COX from oxidatively induced degradation (PubMed:30552096).|||In conditions of increased oxidative stress, the protein is stabilized, increasing its mature intramitochondrial form and thereby protecting COX from oxidatively induced degradation.|||In normal conditions, the cytoplasmic precursor protein is rapidly degraded by the ubiquitination-proteasome system (UPS). Oxidative stress induces protein stabilization and import into mitochondria where it protects COX from degradation.|||Mitochondrion inner membrane|||Mutant mice generated by CRISPR-Cas9-mediated gene editing are born at the expected Mendelian rate. They show impaired motor skills, with decreased motor coordination and endurance. Mutant show global COX deficiency with reduced enzymatic activity, low steady-state levels of structural subunits and defective assembly in all the tested tissues.|||N-terminal mitochondrial targeting sequence is cleaved from the mature protein once in the mitochondrion.|||Required for cytochrome c complex (COX) IV assembly and function Protects COX assembly from oxidation-induced degradation, COX being the terminal component of the mitochondrial respiratory chain. http://togogenome.org/gene/10090:Or9i16 ^@ http://purl.uniprot.org/uniprot/Q8VFQ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aaas ^@ http://purl.uniprot.org/uniprot/P58742 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Female mutants are sterile due to delayed oocyte maturation and meiotic spindle assembly.|||Interacts with NDC1, the interaction is required for nuclear pore localization. Interacts with the inactive form aurora kinase AURKA. Interacts with PGRMC2 (By similarity).|||Nucleus envelope|||Plays a role in the normal development of the peripheral and central nervous system. Required for the correct localization of aurora kinase AURKA and the microtubule minus end-binding protein NUMA1 as well as a subset of AURKA targets which ensures proper spindle formation and timely chromosome alignment.|||Widely expressed. Particularly abundant in cerebellum, corpus callosum, adrenal gland, pituitary gland, gastrointestinal structures and fetal lung.|||nuclear pore complex|||spindle pole http://togogenome.org/gene/10090:Gys2 ^@ http://purl.uniprot.org/uniprot/Q8VCB3 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subunit ^@ Allosteric activation by glucose-6-phosphate. Phosphorylation reduces the activity towards UDP-glucose. When in the non-phosphorylated state, glycogen synthase does not require glucose-6-phosphate as an allosteric activator; when phosphorylated it does (By similarity).|||Belongs to the glycosyltransferase 3 family.|||Expression in the liver oscillates in a circadian manner with peak levels during the night.|||Interacts with GYG1 (via C-terminus); required for GYS2-mediated glycogen synthesis.|||Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CSNK2A2 is required for inhibitory phosphorylation at Ser-641 (site 3a), Ser-645 (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A an GSK3B (By similarity). Dephosphorylation at Ser-641 and Ser-645 by PP1 activates the enzyme (By similarity). Phosphorylation at Ser-8 is not required for interaction with GYG1 (PubMed:24982189). Interaction with GYG1 does not regulate the phosphorylation at Ser-8 and Ser-641 (PubMed:24982189).|||Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan. http://togogenome.org/gene/10090:Susd5 ^@ http://purl.uniprot.org/uniprot/G3UW60 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Tekt1 ^@ http://purl.uniprot.org/uniprot/Q5NBU4|||http://purl.uniprot.org/uniprot/Q9DAJ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tektin family.|||Interacts with TEKT3.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules. Required for normal sperm mobility.|||cilium axoneme|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Apba3 ^@ http://purl.uniprot.org/uniprot/O88888 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the cytoplasmic domain of amyloid protein (APP). Interacts with HIF1AN (via N-terminus) (By similarity). Interacts with NECAB3; seems to mediate the interaction between NECAB3 and HIF1AN (By similarity).|||Composed of an N-terminal domain, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane.|||May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. May enhance the activity of HIF1A in macrophages by inhibiting the activity of HIF1AN (By similarity).|||Ubiquitous.|||perinuclear region http://togogenome.org/gene/10090:Ccnc ^@ http://purl.uniprot.org/uniprot/Q3U6Q7|||http://purl.uniprot.org/uniprot/Q3UXL9|||http://purl.uniprot.org/uniprot/Q62447|||http://purl.uniprot.org/uniprot/Q8CAS3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin C subfamily.|||Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm14819 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Tas2r144 ^@ http://purl.uniprot.org/uniprot/Q7TQB8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5 (By similarity).|||Membrane|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Ifnar1 ^@ http://purl.uniprot.org/uniprot/P33896 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II cytokine receptor family.|||Cell membrane|||Heterodimer with IFNAR2; forming the receptor for type I interferon (By similarity). Interacts with TYK2 (By similarity). Interacts with STAT1 and STAT2 (By similarity). Interacts (serine-phosphorylated form) with FBXW11, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:14532120). 3Interacts with SHMT2; this promotes interaction with ABRAXAS2 and the BRISC complex (By similarity). Interacts with TRIM10; this interaction prevents association between IFNAR1 and TYK2 (By similarity).|||Late endosome|||Lysosome|||Mice are protected from the lethal septic effects of intraperitoneal LPS administration observed in wild-type mice (PubMed:23872679). Double knockout with TREX1 does not show a visible phenotype (PubMed:18724932).|||Phosphorylated on serine residues in response to interferon binding; this promotes interaction with FBXW11 and ubiquitination (PubMed:14532120).|||The interferon signaling pathway is not identical between species. Thus, the interaction with STAT1 and STAT2 may not be conserved in mouse; in human it requires phosphorylation at 'Tyr-466', but the mouse protein has a Phe at the equivalent position. Likewise, cysteine palmitoylation is required for the activation of STAT1 and STAT2 in human, but the Cys is not conserved in mouse.|||Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:14532120, PubMed:1533935, PubMed:24075985). Type I interferon binding activates the JAK-STAT signaling cascade, and triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and the IFNR alpha- and beta-subunits themselves (By similarity). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (By similarity). Can also act independently of IFNAR2: form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (PubMed:23872679).|||Ubiquitinated (PubMed:14532120). This leads to its internalization and lysosomal degradation. The 'Lys-63'-linked ubiquitin chains are cleaved off by the BRISC complex; this prevents receptor internalization and degradation. Probable ubiquitination sites have been identified in human, but are poorly conserved across species. http://togogenome.org/gene/10090:Pnpla5 ^@ http://purl.uniprot.org/uniprot/Q32LZ8 ^@ Function ^@ Has abundant triacylglycerol lipase activity. http://togogenome.org/gene/10090:Fam114a1 ^@ http://purl.uniprot.org/uniprot/Q9D281 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At embryonic days 12 and 15, it is strongly expressed in the ventricular and intermediate zones of the brain and of the spinal cord. At postnatal day 10, it is detected in the dentate gyrus, the hippocampus, the cerebellum and the olfactory bulb.|||Belongs to the FAM114 family.|||Cytoplasm|||May play a role in neuronal cell development.|||Over-expressed in brain. Also detected in lung, stomach, and in a lower extent in testis and thymus. http://togogenome.org/gene/10090:Alkbh7 ^@ http://purl.uniprot.org/uniprot/Q9D6Z0 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Increased body weight and body fat, a phenotype amplified under high-fat diet.|||May function as protein hydroxylase; can catalyze auto-hydroxylation at Leu-110 (in vitro), but this activity may be due to the absence of the true substrate. Required to induce programmed necrosis in response to DNA damage caused by cytotoxic alkylating agents. Acts by triggering the collapse of mitochondrial membrane potential and loss of mitochondrial function that leads to energy depletion and cell death. ALKBH7-mediated necrosis is probably required to prevent the accumulation of cells with DNA damage. Does not display DNA demethylase activity (By similarity). Involved in fatty acid metabolism.|||Mitochondrion matrix|||Widely expressed. http://togogenome.org/gene/10090:Lhfpl6 ^@ http://purl.uniprot.org/uniprot/Q8BM86 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the LHFP family.|||Membrane http://togogenome.org/gene/10090:Or7g32 ^@ http://purl.uniprot.org/uniprot/Q8VFF2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dhh ^@ http://purl.uniprot.org/uniprot/Q544P6|||http://purl.uniprot.org/uniprot/Q61488 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hedgehog family.|||Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in adult testes (PubMed:8805249). Not expressed in limb buds.|||Female mice homozygous for the Dhh gene are fully viable and fertile, whereas male mice are viable but infertile, owing to a complete absence of mature sperm (PubMed:8805249). Male mice exhibit a dramatic reduction in testicular growth (PubMed:8805249). The severity of the phenotype varies depending upon the genetic background of the mice (PubMed:8805249). The majority of the Dhh-null males are pseudohermaphrodites with a blind vaginal opening and evidence of teats. These mice show anastomotic seminiferous tubules, pertitubular cell abnormalities, and absence of adult-type Leydig cells (PubMed:11090455).|||First detected at 11.5 dpc in the presumptive testis (PubMed:8805249). No expression in the ovary at this or any later time (PubMed:8805249). At 12.5 dpc testis expression is confined to Sertoli cells and is not detected in precursors of the androgen-producing interstitial somatic cells (the Leydig cells) (PubMed:8805249). At 13 dpc expressed by Schwann cell precursors both in the dorsal and ventral roots and in the emerging spinal nerves (PubMed:10482238). Expressed in Schwann cells of newborn (PubMed:10482238). Expressed primarily within the valve endocardium at 15.5 dpc with lower levels of expression within the trabeculated endothelium, primary atrial septum and epicardium (PubMed:32151560). Expressed within the valve endocardium at embryonic, fetal and neonatal timepoints with evidence of protein diffusion into the interstitium (PubMed:32151560). Primarily expressed within the atrialis aspect of the anterior and posterior mitral leaflets with the highest signal present at the valve tip (PubMed:32151560).|||Golgi apparatus membrane|||Interacts with BOC and CDON. Interacts with HHIP.|||Membrane|||Multimer.|||N-palmitoylation by HHAT of DhhN is required for desert hedgehog protein N-product multimerization and full activity (By similarity).|||Partially autoproteolyzed (By similarity). The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (DhhN) (By similarity).|||Secreted|||The C-terminal domain regulates the auto-processing and controls the juxtacrine signaling.|||The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (DhhN and DhhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated DhhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Functions in cell-cell mediated juxtacrine signaling (By similarity). Promotes endothelium integrity (PubMed:33063110). Binds to PTCH1 receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes in endothelial cells (PubMed:33063110). In Schwann cells, controls the development of the peripheral nerve sheath and the transition of mesenchymal cells to form the epithelium-like structure of the perineurial tube (PubMed:10482238).|||The C-terminal part of the hedgehog protein precursor displays an autoproteolysis activity that results in the cleavage of the full-length protein into two parts (N-product and C-product). In addition, the C-terminal part displays a cholesterol transferase activity that results by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product.|||The dually lipidated desert hedgehog protein N-product (DhhNp) is essential for a variety of patterning events during development (By similarity). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (PubMed:9811851). Required for normal testis development and spermatogenesis, namely for the formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules (PubMed:8805249, PubMed:11090455). Activates primary cilia signaling on neighboring valve interstitial cells through a paracrine mechanism (PubMed:32151560). May induce motor neurons in lateral neural tube and may have a polarizing activity. Prevents the desert hedgehog protein precursor binding to PTCH1 (By similarity). Binds PTCH2 (PubMed:9811851).|||The dually lipidated hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development. http://togogenome.org/gene/10090:Glud1 ^@ http://purl.uniprot.org/uniprot/P26443|||http://purl.uniprot.org/uniprot/Q3TSQ7 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by SIRT4, leading to inactivate glutamate dehydrogenase activity (PubMed:16959573). Stoichiometry shows that ADP-ribosylation occurs in one subunit per catalytically active homohexamer (By similarity).|||Acetylation of Lys-84 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the Glu/Leu/Phe/Val dehydrogenases family.|||Endoplasmic reticulum|||Homohexamer (By similarity). Interacts with HADH; this interaction inhibits the activation of GLUD1 (PubMed:20670938).|||Mitochondrial glutamate dehydrogenase that converts L-glutamate into alpha-ketoglutarate (PubMed:20670938). Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle (By similarity). Plays a role in insulin homeostasis (PubMed:16959573). May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).|||Mitochondrion|||Subject to allosteric regulation. Activated by ADP. Inhibited by GTP and ATP. ADP can occupy the NADH binding site and activate the enzyme. Inhibited by SIRT4 (By similarity). Inhibited by HADH (PubMed:20670938). http://togogenome.org/gene/10090:Pikfyve ^@ http://purl.uniprot.org/uniprot/Q9Z1T6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylates which inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:11123925). Dephosphorylated by FIG4 in the PI(3,5)P2 regulatory complex, at Ser-48, Ser-1668 and Ser-2052 (By similarity). Phosphorylated in response to insulin at Ser-318 in a protein kinase B (PKB)-dependent manner (PubMed:20513353).|||Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities (PubMed:19037259). Interacts (via chaperonin-like domain) with RABEPK; the interaction recruits RABEPK to the endosomal membrane (PubMed:14530284). Interacts with SPAG9 (PubMed:19056739). Interacts with EGFR (PubMed:17909029).|||Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:19037259, PubMed:22621786, PubMed:17909029). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:10567352, PubMed:10419465). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:22621786, PubMed:10419465). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:11123925) (By similarity). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (By similarity). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (PubMed:31427458, PubMed:25178411). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (By similarity). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (PubMed:23673157, PubMed:22621786). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, trhough association with SPAG9 and RABEPK (PubMed:19056739, PubMed:14530284). Mediates EGFR trafficking to the nucleus (PubMed:17909029).|||Early endosome membrane|||Endosome membrane|||Inhibited by apilimod and YM201636.|||Interaction of FYVE-type domain with phosphatidylinositol 3-phosphate (PtdIns(3)P) is necessary for targeting to the membranes of the late endocytic pathway.|||Knockout embryos die before the 32-64-cell stage (PubMed:21349843). Melanocyte-specific knockout mice exhibit greying of the mouse coat and the accumulation of single membrane vesicle structures in melanocytes resembling multivesicular endosomes (PubMed:29584722). Myeloid cell-specific knockout micedevelop diffuse tissue infiltration of foamy macrophages, hepatosplenomegaly and systemic inflammation (PubMed:31427458). Striated muscle-specific knockout mice exhibit systemic glucose intolerance and insulin resistance at an early age but have unaltered muscle mass. From 10 weeks of age, mice progressively accumulate greater body weight and fat mass (PubMed:23673157). Platelet-specific knockout mice exhibit mild growth delay and body hair loss. Over time, they develop coarse facial features, abdominal distention, an increase in the bulk of their soft tissues and body weight gain. They also have decreased bone mineral density. As mutants aged, they remain infertile and their general body functions deteriorate. The majority die before 28 weeks of age. Animals show massive accelerated arterial thrombosis and organomegaly with inappropriate inflammatory responses characterized by macrophage accumulation in multiple tissues (PubMed:25178411).|||Late endosome membrane|||Phosphorylated in response to insulin at Ser-318 in a protein kinase B (PKB)-dependent manner (PubMed:20513353). Autophosphorylates which down-regulates lipid product formation (PubMed:11123925).|||Ubiquitous.|||phagosome membrane http://togogenome.org/gene/10090:Dse ^@ http://purl.uniprot.org/uniprot/Q8BLI4 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Also has weak activity in the presence of Mg(2+) or Ca(2+) ions.|||Belongs to the dermatan-sulfate isomerase family.|||Converts D-glucuronic acid to L-iduronic acid (IdoUA) residues. Plays an important role in the biosynthesis of the glycosaminoglycan/mucopolysaccharide dermatan sulfate.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Microsome membrane|||N-glycosylated. Glycosylation is important for enzymatic activity. http://togogenome.org/gene/10090:Anln ^@ http://purl.uniprot.org/uniprot/Q8K298 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with F-actin. Interacts with CD2AP. May interact with RHOA. Interacts with FZR1/CDH1 during mitotic exit.|||Nucleus|||Phosphorylated during mitosis.|||Required for cytokinesis. Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis. May play a significant role in podocyte cell migration.|||Ubiquitinated, and this requires FZR1/CDH1.|||bleb|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Rita1 ^@ http://purl.uniprot.org/uniprot/Q9D1H0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RITA family.|||Cytoplasm|||Interacts with RBPJ/RBPSUH.|||Nucleus|||Tubulin-binding protein that acts as a negative regulator of Notch signaling pathway. Shuttles between the cytoplasm and the nucleus and mediates the nuclear export of RBPJ/RBPSUH, thereby preventing the interaction between RBPJ/RBPSUH and NICD product of Notch proteins (Notch intracellular domain), leading to down-regulate Notch-mediated transcription. May play a role in neurogenesis (By similarity).|||centrosome http://togogenome.org/gene/10090:Trpc4ap ^@ http://purl.uniprot.org/uniprot/Q9JLV2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the DCX(TRPC4AP) E3 ubiquitin ligase complex, at least composed of CUL4A, DDB1, TRPC4AP/TRUSS and RBX1 (By similarity). Interacts with MYC (By similarity). Constitutively associated with TNFRSF1A (PubMed:14585990). Directly interacts with TRADD, TRAF2, CHUK, IKBKB and IKBKG (PubMed:16876162, PubMed:14585990). Interacts with TRPC1, TRPC4 and TRPC5 (PubMed:20458742).|||Phosphorylated by GSK3B; phosphorylation is required for ubiquitination.|||Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control. The DCX(TRPC4AP) complex specifically mediates the polyubiquitination and subsequent degradation of MYC as part of the DesCEND (destruction via C-end degrons) pathway. The DesCEND (destruction via C-end degrons) pathway recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The DCX(TRPC4AP) complex specifically recognizes proteins with an arginine at the minus 3 position (R-3 motif) at the C-terminus, such as MYC, leading to their ubiquitination and degradation (By similarity). Also participates in the activation of NFKB1 in response to ligation of TNFRSF1A, possibly by linking TNFRSF1A to the IKK signalosome (PubMed:14585990). Involved in JNK activation via its interaction with TRAF2 (PubMed:16876162). Also involved in elevation of endoplasmic reticulum Ca(2+) storage reduction in response to CHRM1 (PubMed:20458742).|||Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase containing SKP2, leading to its degradation. Phosphorylation by GSK3B is required for ubiquitination.|||Widely expressed, with high levels in heart, liver and testis.|||perinuclear region http://togogenome.org/gene/10090:Dnali1 ^@ http://purl.uniprot.org/uniprot/Q8BVN8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inner dynein arm light chain family.|||Cytoplasm|||Dynein axonemal particle|||Interacts with CFAP45 (By similarity). Interacts with DYNC1H1 (PubMed:16496424).|||May play a dynamic role in flagellar motility.|||Predominantly expressed in the testis, also detected at lower levels in several tissues expressing cilia (PubMed:16496424). Strongly expressed in elongating spermatid cells (at protein level) (PubMed:16496424).|||cilium|||flagellum http://togogenome.org/gene/10090:Cyp26c1 ^@ http://purl.uniprot.org/uniprot/B2RXA7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (Probable) (PubMed:15911617). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (Probable). Catalyzes the oxidation of atRA primarily at C-4 (Probable). Oxidation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination, thereby contributes to the regulation of atRA homeostasis and signaling. Able to metabolize other RAs such as 9-cis with high efficiency (By similarity). Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (Probable). Shares sequence similarity with other CYP26 family members, but has higher affinity to 9-cis-RA and is much less sensitive to the inhibitory effects of ketoconazole (By similarity). In cooperation with Cyp26a1, contributes to the CNS patterning and the development of regions of higher visual acuity (PubMed:15531370, PubMed:17067568).|||Belongs to the cytochrome P450 family.|||During murine development it is initially expressed in the hindbrain and first branchial arch, while in late stages of embryogenesis, it can only be found in tooth buds and in inner ear structures (PubMed:12915310, PubMed:15872003). At E8.0, it is specifically expressed in prospective rhombomeres 2 (r2) and 4 (r4), and in the rostral portion of the first branchial arch (PubMed:12915310, PubMed:15872003). At E8.5 it is expressed in the mid-portion of the neuroepithelium of the prospective hindbrain and the branchial arch ectoderm (PubMed:12915310). By E9.5, its expression is observed in the maxillary and the mandibular components of the first branchial arch, in r2 and in the lateral epibranchial placodes (PubMed:12915310). By E10.5, it displays a specific pattern of expression in the cervical mesenchyme and is restricted to a few cells ventral to the pontine flexure (PubMed:12915310). By E11.5, its expression is confined only to a narrow band in the lateral cervical mesenchyme (PubMed:12915310). At E12.5, it is expressed along the mouth epithelium and at the level of the dental lamina, as well as in the cervical mesenchyme caudal to the otic vesicle (PubMed:12915310). By E14.5 there is strong expression in the dental epithelium (presumptive enamel organ), whereas it almost disappears from the mouth and tongue epithelium (PubMed:12915310). By E15, strongly expressed in a stripe across the retina (PubMed:15531370). At E16.5 expressed only in the enamel organ (specifically the inner dental epithelium) of the various tooth anlagen (PubMed:12915310). At E18.5 it is highly expressed in the second molar, but almost absent in the first molar epithelium (PubMed:12915310). Expression continues for several days postnatally, and persists longer in the temporal than nasal retina, disappearing around P14 (PubMed:15531370).|||Membrane|||The knockout presents no discernible embryological defects, however double homozygous mutants for Cyp26a1/c1 display a more severe RA embryopathy phenotype than either mutant alone, with lethality by E11.0. Among others, this includes CNS patterning abnormalities, a reduced size of the head, eye, frontonasal region and an open neural tube between the fore and hindbrain. http://togogenome.org/gene/10090:Cbln3 ^@ http://purl.uniprot.org/uniprot/Q9JHG0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum|||Expressed in brain, restricted to the cerebellar cortex. Within the cerebellum, expressed in granule layers (at protein level). Also detected in postsynaptic Purkinje cell spines (at protein level).|||Heterohexamer; disulfide-linked heterotrimers (By similarity). Interacts with CBLN1. May also form oligomers with CBLN2 and CBLN4.|||In the developing brain, selectively expressed as early as postnatal day 7-10 in cerebellar granule cells.|||May be involved in synaptic functions in the CNS.|||Secreted|||Synapse|||cis-Golgi network http://togogenome.org/gene/10090:Slc27a2 ^@ http://purl.uniprot.org/uniprot/O35488 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Cell membrane|||Conditional knockout in liver results in decreased long-chain fatty acids (LCFA) uptake by hepatocytes and decreased peroxisomal long chain and very long-chain acyl-CoA synthetase (VLACS) activity.|||Endoplasmic reticulum membrane|||Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes, playing an important role in hepatic fatty acid uptake (PubMed:9671728, PubMed:15699031, PubMed:20530735). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (PubMed:15699031, PubMed:20530735). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis (PubMed:15699031, PubMed:20530735). Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid (By similarity). May contribute to the synthesis of sphingosine-1-phosphate (By similarity). Does not activate C24 bile acids, cholate and chenodeoxycholate (By similarity). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol. However, it is not critical for THCA activation and bile synthesis in vivo (By similarity).|||Microsome|||Peroxisome membrane|||Strong expression in liver and kidney (at protein level) (PubMed:20530735, PubMed:11980911, PubMed:9671728). Lower expression in brain and testis, no expression in skeletal muscle and spleen (PubMed:11980911). Shows uniform distribution in liver acinus (PubMed:11980911). http://togogenome.org/gene/10090:Kifc1 ^@ http://purl.uniprot.org/uniprot/Q9QWT9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. NCD subfamily.|||Binds NUBP1 and NUBP2 (PubMed:16638812). Interacts with PPP1R42 (PubMed:18237440).|||Centrosome amplification as well as multipolar spindles. Cells overexpressing Kifc1 show a single microtubule aster and growth arrest in prometaphase.|||Early endosome|||Highly expressed in 14 dpc embryos, spleen and NIH3T3 cells. Also expressed in testis, brain, lung, kidney and cultured astrocytes. Very low levels in skeletal muscle and heart.|||Highly expressed in hippocampus of 13 dpc embryos declining to low levels by 18 dpc and to undetectable levels in juvenile and adult hippocampus.|||Minus end-directed microtubule-dependent motor required for bipolar spindle formation (PubMed:16638812). May contribute to movement of early endocytic vesicles (PubMed:17360972). Regulates cilium formation and structure (PubMed:23807208).|||Nucleus|||Purified early endocytic vesicles bind minus end-directed Kifc1 as well as plus end-directed Kif5b. Addition of anti-Kifc1 antibodies leads to a decrease in minus end-directed vesicle motility in vitro.|||centrosome|||spindle http://togogenome.org/gene/10090:Cisd1 ^@ http://purl.uniprot.org/uniprot/Q91WS0 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CISD protein family.|||Binds 1 [2Fe-2S] cluster per subunit. The [2Fe-2S] cluster is redox-active and pH labile and is significantly less stable at pH 4.5 as compared with pH 7.0.|||Homodimer.|||L-cysteine transaminase that catalyzes the reversible transfer of the amino group from L-cysteine to the alpha-keto acid 2-oxoglutarate to respectively form 2-oxo-3-sulfanylpropanoate and L-glutamate (By similarity). The catalytic cycle occurs in the presence of pyridoxal 5'-phosphate (PLP) cofactor that facilitates transamination by initially forming an internal aldimine with the epsilon-amino group of active site Lys-55 residue on the enzyme (PLP-enzyme aldimine), subsequently displaced by formation of an external aldimine with the substrate amino group (PLP-L-cysteine aldimine). The external aldimine is further deprotonated to form a carbanion intermediate, which in the presence of 2-oxoglutarate regenerates PLP yielding final products 2-oxo-3-sulfanylpropanoate and L-glutamate. The proton transfer in carbanion intermediate is suggested to be controlled by the active site lysine residue, whereas PLP stabilizes carbanion structure through electron delocalization, also known as the electron sink effect (By similarity). Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (PubMed:17376863). May be involved in iron-sulfur cluster shuttling and/or in redox reactions. Can transfer the [2Fe-2S] cluster to an apo-acceptor protein only when in the oxidation state, likely serving as a redox sensor that regulates mitochondrial iron-sulfur cluster assembly and iron trafficking upon oxidative stress (By similarity).|||Liver, adipose, skeletal muscle and heart (at protein level). Widely expressed. Expressed at the highest levels in the heart.|||Mitochondrion outer membrane|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Zfpl1 ^@ http://purl.uniprot.org/uniprot/Q9DB43 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZFPL1 family.|||Interacts with GOLGA2/GM130.|||Phosphorylated.|||Required for cis-Golgi integrity and efficient ER to Golgi transport. Involved in the maintenance of the integrity of the cis-Golgi, possibly via its interaction with GOLGA2/GM130 (By similarity).|||The B box-type and RING-type zinc fingers although degenerate play a central role in function of the protein.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Fmo6 ^@ http://purl.uniprot.org/uniprot/J3QMN6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FMO family.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Smpd1 ^@ http://purl.uniprot.org/uniprot/Q04519 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Secretion is activated by bacteria such as P. aeruginos, this activation results in the release of ceramide in the outer leaflet of the plasma membrane which facilitates the infection.|||Belongs to the acid sphingomyelinase family.|||Binds 2 Zn(2+) ions per subunit (PubMed:27435900).|||Both lysosomal and secreted forms are glycosylated but they show a differential pattern of glycosylation.|||Converts sphingomyelin to ceramide (PubMed:9660788, PubMed:8706124). Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly. However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form (By similarity).|||Hydrolysis of liposomal sphingomyelin is stimulated by incorporation of diacylglycerol (DAG), ceramide and free fatty acids into the liposomal membranes. Phosphatidylcholine hydrolysis is inhibited by incorporation of cholesterol, ceramide, DAG, monoacylglycerol and fatty acids.|||In the lysosomes, converts sphingomyelin to ceramide. Plays an important role in the export of cholesterol from the intraendolysosomal membranes. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol (PubMed:27435900). Modulates stress-induced apoptosis through the production of ceramide (PubMed:8706124).|||Lipid droplet|||Lysosome|||Monomer (PubMed:27435900). Interacts with SORT1; the interaction is required for SMPD1 targeting to lysosomes (By similarity).|||Mutants infected with Pseudomonas aeruginosa die within 7 days whereas all wild-type mice survive the infection (PubMed:12563314). Mutants are defective in radiation-induced apoptosis (PubMed:8706124).|||Phosphorylated at Ser-506 by PRKCD upon stress stimuli. Phosphorylation is required for secretion.|||Proteolytically processed. Mature lysosomal form arises from C-terminal proteolytic processing of pro-sphingomyelin phosphodiesterase.|||Secreted|||There are two types of sphingomyelinases: ASM (acid), and NSM (neutral).|||This form is generated following cleavage by CASP7 in the extracellular milieu (PubMed:35705808). It shows increased activity (PubMed:35705808).|||This form is generated following cleavage by CASP7 in the extracellular milieu in response to bacterial infection (PubMed:35705808). It shows increased ability to convert sphingomyelin to ceramide and promotes plasma membrane repair. Plasma membrane repair by ceramide counteracts the action of gasdermin-D (GSDMD) perforin (PRF1) pores that are formed in response to bacterial infection (PubMed:35705808).|||When secreted, modulates cell signaling with its ability to reorganize the plasma membrane by converting sphingomyelin to ceramide. Secreted form is increased in response to stress and inflammatory mediators such as IL1B, IFNG or TNF as well as upon infection with bacteria and viruses. Produces the release of ceramide in the outer leaflet of the plasma membrane playing a central role in host defense. Ceramide reorganizes these rafts into larger signaling platforms that are required to internalize P. aeruginosa, induce apoptosis and regulate the cytokine response in infected cells. In wounded cells, the lysosomal form is released extracellularly in the presence of Ca(2+) and promotes endocytosis and plasma membrane repair.|||extracellular space http://togogenome.org/gene/10090:Acbd5 ^@ http://purl.uniprot.org/uniprot/E9QNH7|||http://purl.uniprot.org/uniprot/Q5CZX6|||http://purl.uniprot.org/uniprot/Q5XG73 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters (By similarity).|||Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters.|||Belongs to the ATG37 family.|||Membrane|||Peroxisome membrane http://togogenome.org/gene/10090:Pwwp4d ^@ http://purl.uniprot.org/uniprot/A2BG95 ^@ Similarity ^@ Belongs to the PWWP3A family. http://togogenome.org/gene/10090:Tcerg1l ^@ http://purl.uniprot.org/uniprot/Q3B807 ^@ Sequence Caution ^@ Contaminating sequence. Potential poly-A sequence. http://togogenome.org/gene/10090:Pcare ^@ http://purl.uniprot.org/uniprot/Q6PAC4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Deficient mice develop severe early-onset retinal degeneration associated with a disorganized outer segment, progressive thinning of the outer nuclear layer, microglia activation and non-responsive to light by 8 weeks of age.|||Expressed in the developing eye at 14 dpc.|||Photoreceptor inner segment|||Plays an essential role for normal photoreceptor cell maintenance and vision.|||Specifically expressed in retina.|||photoreceptor outer segment http://togogenome.org/gene/10090:Irf2bp1 ^@ http://purl.uniprot.org/uniprot/Q8R3Y8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities. May act as an E3 ligase towards JDP2, enhancing its polyubiquitination. Represses ATF2-dependent transcriptional activation.|||Belongs to the IRF2BP family.|||Interacts with IRF2. Part of a corepressor complex containing IRF2 and IRF2BP2. Interacts with JDP2.|||Nucleus http://togogenome.org/gene/10090:4930415L06Rik ^@ http://purl.uniprot.org/uniprot/Q3V0Y1 ^@ Similarity ^@ Belongs to the SMEK family. http://togogenome.org/gene/10090:Vmn2r13 ^@ http://purl.uniprot.org/uniprot/L7N1X2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm44504 ^@ http://purl.uniprot.org/uniprot/P21126|||http://purl.uniprot.org/uniprot/Q3UK94 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome.|||Component of the BAG6/BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with BAG6; the interaction is direct and required for UBL4A protein stability. Interacts with USP13; may be indirect via BAG6.|||Nucleus|||Polyubiquitinated. Ubiquitination by AMFR and deubiquitination by USP13 may regulate the interaction between the BAG6/BAT3 complex and SGTA and therefore may regulate client proteins fate.|||cytosol http://togogenome.org/gene/10090:Hnrnpa2b1 ^@ http://purl.uniprot.org/uniprot/O88569 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Asymmetric dimethylation at Arg-266 constitutes the major methylation site (By similarity). According to a report, methylation affects subcellular location and promotes nuclear localization (By similarity). According to another report, methylation at Arg-266 does not influence nucleocytoplasmic shuttling (By similarity).|||Cytoplasm|||Cytoplasmic granule|||Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs. Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm (By similarity). Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts. Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs. Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs (By similarity). Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (By similarity). Also plays a role in the activation of the innate immune response. Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6. In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production (PubMed:31320558).|||Homodimer; dimerization is required for nucleocytoplasmic translocation (PubMed:31320558). Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with IGF2BP1. Interacts with C9orf72. Interacts with DGCR8. Interacts with TARDBP. Interacts with CKAP5. Interacts with TBK1 (PubMed:31320558). Interacts with STING1 (PubMed:31320558). Interacts with SRC (PubMed:31320558). Interacts with PPIA/CYPA (By similarity).|||Nucleus|||Sumoylated in exosomes, promoting miRNAs-binding.|||The disordered region, when incubated at high concentration, is able to polymerize into labile, amyloid-like fibers and form cross-beta polymerization structures, probably driving the formation of hydrogels. In contrast to irreversible, pathogenic amyloids, the fibers polymerized from LC regions disassemble upon dilution. A number of evidence suggests that formation of cross-beta structures by LC regions mediate the formation of RNA granules, liquid-like droplets, and hydrogels.|||extracellular exosome|||nucleoplasm http://togogenome.org/gene/10090:Esrp1 ^@ http://purl.uniprot.org/uniprot/Q3US41 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ESRP family.|||Epithelial cell-specific. Epithelial-specific expression in diverse tissues and organs with particularly notable levels of expression in skin and gastrointestinal epithelia.|||Homozygous knockout mice die soon after birth due to complications from cleft-lip and palate defects. Knockout embryos show alterations in inner ear morphogenesis and auditory hair cell differentiation.|||It is broadly expressed throughout the epithelium of the otic vesicle at embryonic day 10.5 dpc, but it is absent from the surrounding mesenchyme. High expression is detected in sensory and non-sensory epithelial progenitors during cochlear and vestibular morphogenesis, although the level is weaker at later stages of inner ear development.|||Nucleus|||mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Also regulates the splicing of CD44, CTNND1, ENAH, 3 transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of FGFR2 (By similarity). Regulates splicing and expression of genes involved in inner ear development, auditory hair cell differentiation, and cell fate specification in the cochlear epithelium (PubMed:29107558). http://togogenome.org/gene/10090:Or4c106 ^@ http://purl.uniprot.org/uniprot/Q7TR10 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zfp711 ^@ http://purl.uniprot.org/uniprot/E9PUP8|||http://purl.uniprot.org/uniprot/Q8BYM9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Arf2 ^@ http://purl.uniprot.org/uniprot/Q8BSL7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Arf family.|||GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.|||Golgi apparatus http://togogenome.org/gene/10090:Pramel33 ^@ http://purl.uniprot.org/uniprot/A0A0J9YU00 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Cpd ^@ http://purl.uniprot.org/uniprot/O89001 ^@ Cofactor|||Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M14 family.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||There are 3 carboxypeptidase-like domains. Only the first two domains seem to have kept a catalytic activity. http://togogenome.org/gene/10090:Ift57 ^@ http://purl.uniprot.org/uniprot/B2RQZ0|||http://purl.uniprot.org/uniprot/Q8BXG3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT57 family.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:19253336, PubMed:23810713). Interacts with IFT20 (PubMed:12821668). Interacts with IFT88 (PubMed:11062270, PubMed:19253336, PubMed:23810713). Interacts with IFT80, IFT-81, IFT74, IFT172, IFT70B and KIF17 (PubMed:23810713). Interacts with BLOC1S2 (PubMed:18188704). Interacts with RYBP (PubMed:17874297). Interacts with HOMER1; the interaction possibly prevents the pro-apoptotic effects of IFT57 (PubMed:17107665). Interacts with HIP1 (By similarity). In normal conditions, it poorly interacts with HIP1, HIP1 being strongly associated with HTT (By similarity). However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57, leading to apoptosis (By similarity). Interacts with BFAR (By similarity). Interacts with TTC25 (PubMed:25860617). Interacts with USH1G (By similarity).|||Golgi apparatus|||Mice show randomization of the embryo turning process and heart looping, which are hallmarks of defective left-right (LR) axis patterning. Motile monocilia normally present at the surface of the embryonic node, and proposed to initiate the break in LR symmetry, are absent. Furthermore, defects in central nervous system development are observed. The Sonic hedgehog (Shh) pathway is down-regulated in the neural tube, resulting in failure to establish ventral neural cell fate.|||Present in retina and testis. In brain, it is present in the cortex, striatum, globus pallidus, hypothalamus and cerebellum. Present at high level in neurons and neuropil throughout the brain (at protein level). Expressed in hippocampal neurons, where it colocalizes with HOMER1 at postsynaptic regions.|||Required for the formation of cilia. Plays an indirect role in sonic hedgehog signaling, cilia being required for all activity of the hedgehog pathway. Has pro-apoptotic function via its interaction with HIP1, leading to recruit caspase-8 (CASP8) and trigger apoptosis. Has the ability to bind DNA sequence motif 5'-AAAGACATG-3' present in the promoter of caspase genes such as CASP1, CASP8 and CASP10, suggesting that it may act as a transcription regulator; however the relevance of such function remains unclear.|||The pseudo DED region (pDED) mediates the interaction with HIP1.|||Ubiquitous through the epiblast. Expression is detected in mesoderm and most strongly in ectoderm, but not in endoderm. Highly expressed in the region of the node, a depression at the surface of the embryo proposed to have a role in left-right axis patterning. At 8.5 dpc, it is widely expressed except in the heart. Stronger expression is observed in the anterior midline, the forebrain and the somites. Strong expression remains in the forebrain at 9.5 dpc and 10.5 dpc and extends to all regions of the neural tube. At those stages, high expression is also found in the branchial arches and in the limb buds. Embryo section at 9.5 dpc also shows expression throughout the neural tube and the mesoderm, but not in the surface ectoderm. The strongest expression is observed on the luminal edge of the neural tube and in the ventral foregut.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Bphl ^@ http://purl.uniprot.org/uniprot/Q8R164 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Cytoplasm|||Monomer. May also form homodimers (By similarity).|||Serine hydrolase that catalyzes the hydrolytic activation of amino acid ester prodrugs of nucleoside analogs such as valacyclovir and valganciclovir. Activates valacyclovir to acyclovir. May play a role in detoxification processes. It is a specific alpha-amino acid ester hydrolase that prefers small, hydrophobic, and aromatic side chains and does not have a stringent requirement for the leaving group other than preferring a primary alcohol (By similarity). http://togogenome.org/gene/10090:Pax8 ^@ http://purl.uniprot.org/uniprot/Q00288 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the developing excretory system and the thyroid gland.|||Interacts with WWTR1.|||Nucleus|||Thought to encode a transcription factor. It may have a role in kidney cell differentiation. May play a regulatory role in mammalian development. http://togogenome.org/gene/10090:Nr1h5 ^@ http://purl.uniprot.org/uniprot/A0A0G2JEJ9|||http://purl.uniprot.org/uniprot/A0A0G2JG67|||http://purl.uniprot.org/uniprot/E9Q5A6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Nucleus http://togogenome.org/gene/10090:Cd209a ^@ http://purl.uniprot.org/uniprot/Q91ZX1 ^@ Caution|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Down-regulated upon activation of dendritic cells.|||In mouse, 5 genes homologous to human CD209/DC-SIGN and CD209L/DC-SIGNR have been identified. Mouse CD209A product was named DC-SIGN by PubMed:11581173 because of its similar expression pattern and chromosomal location in juxtaposition to CD23, but despite of the low sequence similarity.|||Membrane|||Predominantly expressed in dendritic cells. Detected at very low levels in lung, spleen, lymph nodes and bone marrow.|||Probable pathogen-recognition receptor. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. May recognize in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens. http://togogenome.org/gene/10090:Zfhx3 ^@ http://purl.uniprot.org/uniprot/E9QMD3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pcdha1 ^@ http://purl.uniprot.org/uniprot/Q91Y21 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dynlrb1 ^@ http://purl.uniprot.org/uniprot/A2AVR9|||http://purl.uniprot.org/uniprot/P62627 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.|||Belongs to the GAMAD family.|||Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer.|||Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNLRB2. Interacts with DYNC1I1 and DYNC1I2. Interacts with RAB6A isoform 1 (GTP-bound); the interaction is direct. Interacts with RAB6A isoform 2 (GDP-bound); the interaction is direct. Interacts with RAB6B (GDP-bound).|||cytoskeleton http://togogenome.org/gene/10090:Spry4 ^@ http://purl.uniprot.org/uniprot/Q9WTP2 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8 dpc expressed in the lateral plate mesoderm of the primitive streak. At 9.5 and 10.5 dpc expressed in the nasal placodes, maxillary and mandibular processes, posterior part of the hyoid arch and the progress zone of the limb buds and the presomitic mesoderm. At 11.5 dpc expressed in the dorso-lateral region of the somites (mostly in the myotome) and in the otic vesicle. At 11.5 and 12.5 dpc expressed in the distal lung mesenchyme, with a strong expression in the accessory lobe of the lung.|||Belongs to the sprouty family.|||By FGF signaling.|||Cytoplasm|||Expressed in the embryo and adult tissues including heart, brain, lung, kidney, and skeletal muscle.|||Interacts (via C-terminus) with TESK1 (via both C- and N-termini); the interaction inhibits TESK1 kinase activity (PubMed:17974561). Interacts with RAF1 (By similarity). Interacts with CAV1 (via C-terminus) (PubMed:16877379).|||Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Probably impairs the formation of GTP-Ras (By similarity). Inhibits Ras-independent, but not Ras-dependent, activation of RAF1 (By similarity). Represses integrin-mediated cell spreading via inhibition of TESK1-mediated phosphorylation of cofilin (By similarity).|||The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.|||ruffle membrane http://togogenome.org/gene/10090:Cyp4a14 ^@ http://purl.uniprot.org/uniprot/O35728 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:17112342). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:17112342). Catalyzes the hydroxylation of saturated carbon hydrogen bonds of fatty acids (PubMed:17112342). May act as a major omega- and ommega-1 hydroxylase for dodecanoic (lauric) acid in kidney (PubMed:17112342). Catalyzes with low efficiency the epoxidation of 11,12-double bond of arachidonic acid (PubMed:17112342).|||Belongs to the cytochrome P450 family.|||By peroxisome proliferator methylclofenapate; 1000-fold in liver, 10-fold in kidney.|||Endoplasmic reticulum membrane|||Gender- and strain-specific expression in kidney (at protein level). Predominantly expressed in females, the expression among strains decreasing in the following order: FVB/N > NMRI > Balb/c > 129 Sv/J > C57BL/6 (PubMed:17112342). Expressed at very low level in liver, kidney and spleen of both male and female C57BL/6 X CBA hybrid mice (PubMed:9271096).|||Microsome membrane http://togogenome.org/gene/10090:Snx30 ^@ http://purl.uniprot.org/uniprot/Q8CE50 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Early endosome membrane|||Heterodimer; heterodimerizes with SNX4.|||Involved in the regulation of endocytosis and in several stages of intracellular trafficking. Together with SNX4, involved in autophagosome assembly. http://togogenome.org/gene/10090:Echs1 ^@ http://purl.uniprot.org/uniprot/Q8BH95 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of Lys-101 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the enoyl-CoA hydratase/isomerase family.|||Converts unsaturated trans-2-enoyl-CoA species ((2E)-enoyl-CoA) to the corresponding (3S)-3-hydroxyacyl-CoA species through addition of a water molecule to the double bond. Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (By similarity). Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA ((2E)-2-methylpropenoyl-CoA). Can bind tiglyl-CoA (2-methylcrotonoyl-CoA), but hydrates only a small amount of this substrate (By similarity). Plays a key role in the beta-oxidation spiral of short- and medium-chain fatty acid oxidation. At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity).|||Homohexamer; dimer of trimers.|||Mitochondrion matrix http://togogenome.org/gene/10090:Or8k24 ^@ http://purl.uniprot.org/uniprot/Q7TR74 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Yaf2 ^@ http://purl.uniprot.org/uniprot/Q99LW6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to MYC and inhibits MYC-mediated transactivation. Also binds to MYCN and enhances MYCN-dependent transcriptional activation. Increases calpain 2-mediated proteolysis of YY1 in vitro. Component of the E2F6.com-1 complex, a repressive complex that methylates 'Lys-9' of histone H3, suggesting that it is involved in chromatin-remodeling.|||Expressed in both pre- and post-implantation embryos.|||In the mesoderm, expressed in the region close to the surface ectoderm.|||Interacts with MYC, MYCN, RNF2/RING1B and YY1. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, L3MBTL2 and YAF2.|||Nucleus http://togogenome.org/gene/10090:Or4c15b ^@ http://purl.uniprot.org/uniprot/Q7TQZ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Asmt ^@ http://purl.uniprot.org/uniprot/D3KU66 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family.|||Catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine).|||Exhibits very subtle night/day variation, if any.|||Expressed predominantly in the pineal gland (at protein level). Very low expression, if any, in the retina.|||Homodimer.|||Pineal melatonin synthesis is severely compromised in most inbred strains. In many inbred strains, genetic defects in ASMT have been identified. Melatonin production may have an impact on gonadal development, testis development being significantly promoted in melatonin-deficient C57BL/6J x Mus musculus molossinus animals (PubMed:20308563). http://togogenome.org/gene/10090:Ambra1 ^@ http://purl.uniprot.org/uniprot/A2AH22 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8.5 dpc, it is detected throughout the neuroepithelium (PubMed:17589504). At 11.5 dpc, it is highly expressed in the ventral-most part of the spinal cord, the encephalic vesicles, the neural retina, the limbs and the dorsal root ganglia (PubMed:17589504). Later, it is expressed in the entire developing nervous system as well as in other tissues (PubMed:17589504). In brain, strong expression is observed in the cortex, hippocampus and striatum of postnatal brain (PubMed:17589504).|||Belongs to the WD repeat AMBRA1 family.|||Component of the DCX(AMBRA1) E3 ubiquitin ligase complex, also named CRL4(AMBRA1), at least composed of CUL4 (CUL4A or CUL4B), DDB1, AMBRA1 and RBX1 (PubMed:23974797). Interacts with BECN1 (PubMed:17589504, PubMed:23974797). Probably forms a complex with BECN1 and PIK3C3 (PubMed:17589504). Interacts with BECN2 (By similarity). Interacts with BCL2; leading to prevent interaction with BCN1 and autophagy, interaction is disrupted upon autophagy induction (By similarity). Interacts with ULK1 (By similarity). Interacts (via PxP motifs) with PPP2CA; enhancing interaction between PPP2CA and MYC or FOXO3 (PubMed:25438055). Forms a complex with PPP2CA and BECN1 (By similarity). Interacts (TQT motifs) with DYNLL1 and DYNLL2; tethering AMBRA1 and the BECN1-PIK3C3 complex in absence of autophagy (By similarity). Interacts with TRAF6; interaction is required to mediate 'Lys-63'-linked ubiquitination of ULK1 (By similarity). Interacts with TRIM32; promoting activation of ULK1 by TRIM32 via unanchored 'Lys-63'-linked polyubiquitin chains (By similarity). Interacts with PRKN (PubMed:21753002). Interacts (via LIR motif) with LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C) (By similarity). Interacts with HUWE1 (By similarity). Interacts with PTK2/FAK (PubMed:28362576). Interacts with SRC; required for SRC trafficking to autophagosomes (PubMed:28362576).|||Embryonic lethality: mice display severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death (PubMed:17589504). Cells show an accumulation of cyclin-D proteins (Ccnd1, Ccnd2 and Ccnd3), correlated with an increase in retinoblastoma (RB) protein family phosphorylation, leading to increased cell proliferation (PubMed:33854232, PubMed:33854235). Conditional knockout mice lacking Ambra1 in the nervous system display an increase in the volume of the cortex and the lateral ventricles, associated with an enhanced rate of proliferation in the whole 13.5 dpc brain and in the olfactory bulbs of the 18.5 dpc brain (PubMed:33854232). Ambra1 deletion in a mouse lung cancer model leads to increased cell proliferation, formation of replication stress and chek1/Chk1 activation; cells are hypersensitive to chek1/Chk1 inhibition (PubMed:33854232). Impaired regulatory T-cells (Treg) differentiation, leading to worsen disease pathogenesis in a mouse model of multiple sclerosis (PubMed:30513302).|||Endoplasmic reticulum|||Expressed throughout the brain, including midbrain and striatum.|||Mitochondrion|||Nucleus|||Phosphorylation at Ser-52 by MTOR inhibits its ability to regulate autophagy and mediate ubiquitination of ULK1. Phosphorylation by ULK1 in response to autophagy induction abolishes interaction with DYNLL1 and DYNLL2, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation. Phosphorylation by MTOR inhibits interaction with PPP2CA and subsequent dephosphorylation of MYC. Phosphorylation at Ser-1044 by CHUK/IKKA promotes its interaction with ATG8 family proteins GABARAP and MAP1LC3B and its mitophagic activity.|||Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy (PubMed:17589504, PubMed:33854232, PubMed:33854235, PubMed:33854239). The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins such as BECN1, CCND1, CCND2, CCND3, ELOC and ULK1 (PubMed:23974797, PubMed:33854232, PubMed:33854235, PubMed:33854239). Acts as an upstream master regulator of the transition from G1 to S cell phase: AMBRA1 specifically recognizes and binds phosphorylated cyclin-D (CCND1, CCND2 and CCND3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation (PubMed:33854232, PubMed:33854235, PubMed:33854239). By controlling the transition from G1 to S phase and cyclin-D degradation, AMBRA1 acts as a tumor suppressor that promotes genomic integrity during DNA replication and counteracts developmental abnormalities and tumor growth (PubMed:33854232, PubMed:33854235, PubMed:33854239). AMBRA1 also regulates the cell cycle by promoting MYC dephosphorylation and degradation independently of the DCX(AMBRA1) complex: acts via interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA), which enhances interaction between PPP2CA and MYC, leading to MYC dephosphorylation and degradation (PubMed:25438055). Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (By similarity). Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation (PubMed:17589504). In normal conditions, AMBRA1 is tethered to the cytoskeleton via interaction with dyneins DYNLL1 and DYNLL2 (By similarity). Upon autophagy induction, AMBRA1 is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy (By similarity). The DCX(AMBRA1) complex mediates 'Lys-63'-linked ubiquitination of BECN1, increasing the association between BECN1 and PIK3C3 to promote PIK3C3 activity (PubMed:23974797). In collaboration with TRAF6, AMBRA1 mediates 'Lys-63'-linked ubiquitination of ULK1 following autophagy induction, promoting ULK1 stability and kinase activity (By similarity). Also activates ULK1 via interaction with TRIM32: TRIM32 stimulates ULK1 through unanchored 'Lys-63'-linked polyubiquitin chains (By similarity). Also acts as an activator of mitophagy via interaction with PRKN and LC3 proteins (MAP1LC3A, MAP1LC3B or MAP1LC3C); possibly by bringing damaged mitochondria onto autophagosomes (PubMed:21753002, PubMed:25215947). Also activates mitophagy by acting as a cofactor for HUWE1; acts by promoting HUWE1-mediated ubiquitination of MFN2 (By similarity). AMBRA1 is also involved in regulatory T-cells (Treg) differentiation by promoting FOXO3 dephosphorylation independently of the DCX(AMBRA1) complex: acts via interaction with PPP2CA, which enhances interaction between PPP2CA and FOXO3, leading to FOXO3 dephosphorylation and stabilization (PubMed:28789945, PubMed:30513302). May act as a regulator of intracellular trafficking, regulating the localization of active PTK2/FAK and SRC (PubMed:28362576). Also involved in transcription regulation by acting as a scaffold for protein complexes at chromatin (PubMed:32616651).|||The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP and MAP1LC3B.|||The PxP motifs mediate interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA).|||The TQT motifs mediate interaction with the dynein light chain proteins DYNLL1 and DYNLL2, tethering AMBRA1 to the cytoskeleton in absence of autophagy.|||Ubiquitinated by RNF2 via 'Lys-48'-linkage in unstressed cells, leading to its degradation by the proteasome (PubMed:24980959). Induction of autophagy promotes stabilization via interaction with CUL4 (CUL4A or CUL4B) and DDB1. Upon prolonged starvation, ubiquitinated and degraded, terminating the autophagy response (By similarity).|||Undergoes proteolytic processing by caspase-6 (CASP6), caspase-7 (CASP7) and caspase-8 (CASP8) during apoptosis, resulting in the dismantling of the autophagic machinery and the accomplishment of the programmed cell death program. Also cleaved by calpains during apoptosis, which mediate a complete proteolytic degradation.|||autophagosome|||cytoskeleton|||cytosol|||focal adhesion http://togogenome.org/gene/10090:Zfp775 ^@ http://purl.uniprot.org/uniprot/Q8BI73 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Klc4 ^@ http://purl.uniprot.org/uniprot/Q9DBS5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the kinesin light chain family.|||Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (By similarity).|||Oligomeric complex composed of two heavy chains and two light chains.|||cytoskeleton http://togogenome.org/gene/10090:Grem2 ^@ http://purl.uniprot.org/uniprot/O88273|||http://purl.uniprot.org/uniprot/Q3TST1 ^@ Caution|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DAN family.|||Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells.|||Expressed in commissural neurons in the developing spinal cord (PubMed:9639362). Expressed during the development of teeth and hair follicles (PubMed:26416033).|||Highly expressed in the ovary, followed by brain, spleen, colon, kidney and uterus. In ovary expressed in granulosa cells of selective early antral follicles.|||Homodimer. Interacts with BMP2, BMP4 and BMP7, but has lower affinity for BMP7 than for BMP2 and BMP4. Binds heparin; this impairs the interaction with BMP2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Secreted|||Up-regulated by gonadotropin treatment. http://togogenome.org/gene/10090:Pramel49 ^@ http://purl.uniprot.org/uniprot/J3QMM8 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Bcl2 ^@ http://purl.uniprot.org/uniprot/P10417|||http://purl.uniprot.org/uniprot/Q6NTH7|||http://purl.uniprot.org/uniprot/Q8BQK4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ BH1 and BH2 domains are required for the interaction with BAX and for anti-apoptotic activity.|||Belongs to the Bcl-2 family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in a variety of tissues.|||Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 (the 'Ser-338' and 'Ser-339' phosphorylated form). Interacts (via the BH4 domain) with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2 (By similarity). Interacts with EI24. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex. Interacts with PPIF; the interaction is impaired by CsA (By similarity). Interacts with BOP (By similarity). Interacts with the SCF(FBXO10) complex (By similarity). Interacts (via the loop between motifs BH4 and BH3) with NLRP1 (via LRR repeats) (By similarity). Interacts with GIMAP3/IAN4 and GIMAP4/IAN1 (PubMed:16509771). Also interacts with GIMAP5/IAN5 (PubMed:16509771, PubMed:21502331). Interacts with BCAP31 (By similarity). Interacts with IRF3 (By similarity). Interacts with BECN1; thereby inhibiting autophagy in non-starvation conditions (By similarity). Interacts with AMBRA1; thereby inhibiting autophagy (By similarity).|||In response to intraperitoneal injection of muramyl dipeptide (MDP), knockout animals show lower serum IL1B levels than wild type. Mutant macrophages release 30% less IL1B than the wild-type cells.|||Membrane|||Mitochondrion outer membrane|||Monoubiquitinated by PRKN, leading to an increase in its stability (By similarity). Ubiquitinated by SCF(FBXO10), leading to its degradation by the proteasome (By similarity).|||Nucleus membrane|||Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity (PubMed:9115213). Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle (PubMed:9115213). In the absence of growth factors, BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases (PubMed:9115213). Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-84, wich stimulates starvation-induced autophagy (By similarity). Dephosphorylated by protein phosphatase 2A (PP2A) (PubMed:9852076).|||Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity, causes the release of cytochrome c into the cytosol promoting further caspase activity.|||Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). Also acts as an inhibitor of autophagy: interacts with BECN1 and AMBRA1 during non-starvation conditions and inhibits their autophagy function (By similarity). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).|||The BH3 motif is required for XIAP-mediated ubiquitination and subsequent induction of apoptosis.|||The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3.|||The loop between motifs BH4 and BH3 is required for the interaction with NLRP1. http://togogenome.org/gene/10090:Axin1 ^@ http://purl.uniprot.org/uniprot/E9QMJ8|||http://purl.uniprot.org/uniprot/O35625|||http://purl.uniprot.org/uniprot/Q14DJ8 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination and subsequent activation of the Wnt signaling pathway (By similarity).|||Cell membrane|||Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also a component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.|||Cytoplasm|||Expressed in embryonic stem cells.|||Homodimer (PubMed:17681137). Component of the beta-catenin destruction complex, containing at least CTNNB1, an axin and GSK3B, that regulates CTNNB1 protein levels through phosphorylation and ubiquitination (By similarity). Interacts with GSK3B; the interaction hyperphosphorylates CTNNB1 leading to its ubiquitination and destruction (By similarity). Interacts with DAXX; the interaction stimulates the interaction of DAXX with TP53, stimulates 'Ser-46' phosphorylation of TP53 and induces cell death on UV irradiation (By similarity). Also interacts with APC, RNF111, SMAD6 and SMAD7 (By similarity). Interacts (via the C-terminal) with PPP1CA; the interaction dephosphorylates AXIN1 and regulates interaction with GSK3B (By similarity). Interacts with PPP2CA; the interaction dephosphorylates AXIN1 (By similarity). Interacts with MDFI; the interaction decreases AXIN1-mediated JUN N-terminal kinase (JNK) activation (By similarity). Interacts with MDFIC; the interaction inhibits beta-cateninin-mediated signaling and AXIN1-mediated JUN N-terminal kinase (JNK) activation (By similarity). Binds ANKRD6, PIAS1, PIAS2, PIAS4, SUMO1, MAP3K1 and MAP3K4 (PubMed:12183362, PubMed:12223491). Component of the AXIN1-HIPK2-TP53 complex (PubMed:15526030). Interacts directly in the complex with TP53 and HIPK2 (PubMed:15526030). Interacts with DIXDC1; the interaction prevents interaction with MAP3K1 (PubMed:15262978). Interacts with AIDA; the interaction blocks the AXIN1-mediated JNK activation through disrupting AXIN1 homodimerization and Wnt signaling (PubMed:17681137). Interacts with LRP5 (via its phosphorylated PPPSP motifs); the interaction is stimulated by WNT1 and GSK3B and activates beta-catenin signaling (PubMed:11336703). Interacts with CTNNB1 (via the armadillo repeats 2-7) (PubMed:10581160, PubMed:15063782). Interacts with MACF1 (By similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with TNKS (By similarity). Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction (PubMed:19581931). Interacts with ZBED3 (via PPPSP motif); the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations (PubMed:19141611). Interacts with WDR26 (By similarity). Interacts with GID8 (By similarity). Interacts with SIAH1 and SIAH2; both probably catalyze AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin-dependent degradation. Interaction with GSK3B and AXIN1 is competitive (By similarity).|||Membrane|||Nucleus|||Phosphorylation and dephosphorylation of AXIN1 regulates assembly and function of the beta-catenin complex. Phosphorylated by CK1 and GSK3B. Dephosphorylated by PPP1CA and PPP2CA. Phosphorylation by CK1 enhances binding of GSK3B to AXIN1 (By similarity). Also phosphorylated by CDK2 which regulates interaction with CTNBB1.|||The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2.|||Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway. Deubiquitinated by USP34, deubiquitinated downstream of beta-catenin stabilization step: deubiquitination is important for nuclear accumulation during Wnt signaling to positively regulate beta-catenin (CTNBB1)-mediated transcription (By similarity). Sumoylation at Lys-858 and Lys-861 prevents ubiquitination and degradation. Sumoylation is required for AXIN1-mediated JNK activation. Ubiquitination by SIAH1 and SIAH2 induces its proteasomal degradation as part of the activation of the Wnt signaling pathway (By similarity).|||Widely expressed at 10.5 dpc to 16.5 dpc. http://togogenome.org/gene/10090:Fdx1 ^@ http://purl.uniprot.org/uniprot/P46656 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adrenodoxin/putidaredoxin family.|||Binds 1 [2Fe-2S] cluster.|||Essential for the synthesis of various steroid hormones, participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis. Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage. Does not form a ternary complex with adrenodoxin reductase and CYP11A1 but shuttles between the two enzymes to transfer electrons.|||Interacts with CYP11A1.|||Mitochondrion matrix http://togogenome.org/gene/10090:C2cd4c ^@ http://purl.uniprot.org/uniprot/Q5HZI2 ^@ Similarity ^@ Belongs to the C2CD4 family. http://togogenome.org/gene/10090:Fgg ^@ http://purl.uniprot.org/uniprot/Q3UEM7|||http://purl.uniprot.org/uniprot/Q3UER8|||http://purl.uniprot.org/uniprot/Q8VCM7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure.|||Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers (By similarity).|||Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain (By similarity).|||Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain.|||Secreted|||Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix (By similarity). Fibrin has a major function in hemostasis as one of the primary components of blood clots (By similarity). In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization (By similarity). Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo (By similarity). Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway (PubMed:19332769). Maternal fibrinogen is essential for successful pregnancy (By similarity). Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage (By similarity). May also facilitate the immune response via both innate and T-cell mediated pathways (By similarity). http://togogenome.org/gene/10090:Vps16 ^@ http://purl.uniprot.org/uniprot/G3X8X7|||http://purl.uniprot.org/uniprot/Q8BWV2|||http://purl.uniprot.org/uniprot/Q8C016 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the VPS16 family.|||Early endosome|||Late endosome membrane|||Lysosome membrane|||Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes.|||Vesicle http://togogenome.org/gene/10090:Serpina3m ^@ http://purl.uniprot.org/uniprot/Q03734 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the serpin family.|||Expressed in liver and testis.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the serpin reactive site and the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina3 paralogs may determine target protease specificity.|||The single human alpha1-antichymotrypsin gene (SERPINA3) is represented by a cluster of 14 individual murine paralogs. http://togogenome.org/gene/10090:Npc1l1 ^@ http://purl.uniprot.org/uniprot/A3KMG9|||http://purl.uniprot.org/uniprot/Z4YJC9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the patched family.|||Membrane http://togogenome.org/gene/10090:Hspb9 ^@ http://purl.uniprot.org/uniprot/G3UWB9|||http://purl.uniprot.org/uniprot/Q9DAM3 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small heat shock protein (HSP20) family.|||Cytoplasm|||Expressed notably in the spermatogenic cells from late pachytene spermatocyte stage till elongate spermatid stage.|||Nucleus|||Testis specific. http://togogenome.org/gene/10090:Psat1 ^@ http://purl.uniprot.org/uniprot/Q3U6K9|||http://purl.uniprot.org/uniprot/Q543K5|||http://purl.uniprot.org/uniprot/Q99K85 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. SerC subfamily.|||Binds 1 pyridoxal phosphate per subunit.|||Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine.|||Homodimer. http://togogenome.org/gene/10090:Spice1 ^@ http://purl.uniprot.org/uniprot/Q8C804 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with CEP120.|||Regulator required for centriole duplication, for proper bipolar spindle formation and chromosome congression in mitosis.|||centriole|||spindle http://togogenome.org/gene/10090:Ep400 ^@ http://purl.uniprot.org/uniprot/Q8CHI8 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family. SWR1 subfamily.|||Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. May also participate in the formation of NuA4 related complexes which lack the KAT5/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. The NuA4 complex interacts with MYC. EP400 interacts with TRRAP, RUVBL1 and RUVBL2. Component of a SWR1-like complex (By similarity). Interacts with ZNF42. Interacts with PHF5A.|||Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. May be required for transcriptional activation of E2F1 and MYC target genes during cellular proliferation. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (By similarity). Regulates transcriptional activity of ZNF42.|||Expressed in brain, thymus, lung, liver, spleen, kidney, colon and bone marrow.|||Intron retention.|||Nucleus http://togogenome.org/gene/10090:Rpl8 ^@ http://purl.uniprot.org/uniprot/P62918 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL2 family.|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with CRY1 (PubMed:19129230).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm|||Hydroxylated on His-216 by RIOX1. The modification is impaired by hypoxia. http://togogenome.org/gene/10090:Serpinb13 ^@ http://purl.uniprot.org/uniprot/Q8CDC0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||May play a role in the proliferation or differentiation of keratinocytes. http://togogenome.org/gene/10090:Sult2b1 ^@ http://purl.uniprot.org/uniprot/O35400 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Expressed at high levels in epididymis, intestine and uterus, and low levels in brain and hypothalamus (PubMed:9647753). Isoform 2 is most prominent in the brain and spinal cord, with modest expression in the lung, skin and spleen (PubMed:12639899). Isoform 1 is most prominently expressed in skin and small intestine, with modest expression in muscle and prostate (PubMed:12639899).|||Isoform 1 and isoform 2 are expressed from stages 8.5-19 dpc.|||Microsome|||Nucleus|||Strongly sulfonates pregnenolone, however is capable to sulfonate cholesterol with a high degree of efficiency. DHEA is a relatively poor substrate.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation. Preferentially sulfonates cholesterol (PubMed:12639899). Catalyzes sulfation of the 3beta-hydroxyl groups of steroids, such as, pregnenolone and dehydroepiandrosterone (DHEA). Cholesterol sulfation is approximately 10-fold higher than for pregnenolone and 20-fold higher than for DHEA (PubMed:12639899). Plays a role in epidermal cholesterol metabolism and in the regulation of epidermal proliferation and differentiation (By similarity).|||cytosol http://togogenome.org/gene/10090:Satb2 ^@ http://purl.uniprot.org/uniprot/Q546B3|||http://purl.uniprot.org/uniprot/Q8VI24 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CUT homeobox family.|||Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Required for the initiation of the upper-layer neurons (UL1) specific genetic program and for the inactivation of deep-layer neurons (DL) and UL2 specific genes, probably by modulating Bcl11b expression. Repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex. May play an important role in palate formation. Acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.|||Expressed in cortical neurons that extend axons across the corpus callosum. Also expressed in branchial arches and in cells of the osteoblast lineage, but not in chondrocytes and osteoclasts.|||Expression first detected at 10.5 dpc in the maxillary component of the first pharyngeal arch and the lateral aspect of the frontonasal process in the regions that will subsequently fuse to form the primary palate. At 11 - 11.5 dpc, the expression pattern demarcates the region of the medial aspect of the maxillary process within the primitive oral cavity, which will form the palate shelf. By 12.5 dpc, symmetrical expression is seen in the medial edges of the developing palate shelves and this continues until 13.5 dpc when the strongest expression is in the mesenchyme underlying the medial edge epithelia. By the time of palatal shelf fusion at 14.5 dpc the expression is dramatically down-regulated. No expression detected elsewhere in the embryo at any stage examined.|||Interacts with PIAS1 (By similarity). Interacts with ATF4 and RUNX2; resulting in enhanced DNA binding and transactivation by these transcription factors.|||Malformations in 2 of the major axonal tracts interconnecting the cortical hemispheres: the corpus callosum (c.c) and the anterior commissure (a.c). Misrouted afferent and efferent cortical axon connections. Impaired migration of upper-layer neurons. Ectopic expression of Ctip2. Craniofacial abnormalities and defects in osteoblast differentiation and function.|||Nucleus|||Nucleus matrix|||Sumoylated by PIAS1. Sumoylation promotes nuclear localization, but represses transcription factor activity (By similarity). http://togogenome.org/gene/10090:Fam184b ^@ http://purl.uniprot.org/uniprot/Q0KK56 ^@ Similarity ^@ Belongs to the FAM184 family. http://togogenome.org/gene/10090:Cdk10 ^@ http://purl.uniprot.org/uniprot/Q0VH02|||http://purl.uniprot.org/uniprot/Q3UMM4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||CDK10 knockout results in partial prenatal lethality. Surviving mice display severe growth retardation, a reduced volume of mineralized matrix in the head, femur, tibia and fibula, bifidity or clefting of C1 (atlas) or C2 (axis), and absence of the dens. Additional defects are present in the kidney, lung, heart, spleen, liver, and muscle. At cellular level, CDK10 knockout does not affect cell proliferation. However, knocked-out mouse embryonic fibroblasts (MEFs) develop longer cilia.|||Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells). Involved in the regulation of actin cytoskeleton organization through the phosphorylation of actin dynamics regulators such as PKN2. Is a negative regulator of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling.|||Heterodimer with CCNQ, the interaction is required for kinase activity. Interacts with ETS2. Interacts with PRK2.|||cilium basal body http://togogenome.org/gene/10090:Lpgat1 ^@ http://purl.uniprot.org/uniprot/E9QL80|||http://purl.uniprot.org/uniprot/Q3UZK0|||http://purl.uniprot.org/uniprot/Q6A0A4|||http://purl.uniprot.org/uniprot/Q91YX5 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Endoplasmic reticulum membrane|||Lysophospholipid acyltransferase involved in fatty acyl chain remodeling of glycerophospholipids in the endoplasmic reticulum membrane (PubMed:35131264). Selectively catalyzes the transfer and esterification of saturated long-chain fatty acids from acyl-CoA to the sn-1 position of 1-lyso-2-acyl phosphatidylethanolamines (1-lyso-PE, LPE), with a preference for stearoyl CoA over palmitoyl CoA as acyl donor (PubMed:36049524). Acts in concert with an unknown phospholipase A1 to convert palmitate PE species into stearate ones. Provides substrates to the PE methylation pathway, controlling stearate/palmitate composition of PE and phosphatidylcholine (PC) species with an overall impact on de novo hepatic lipid synthesis, body fat content and life span (PubMed:35131264). Can acylate lysophosphatidylglycerols (LPG) using various saturated fatty acyl-CoAs as acyl donors (By similarity). Can also acylate monoacylglycerols with a preference for 2-monoacylglycerols over 1-monoacylglycerols (PubMed:20018982, PubMed:35131264). Has no activity toward lysophosphatidic acids (LPA) and lysophosphatidylcholines (LPC) (PubMed:35131264).|||Mice are born at the expected Mendelian frequency. They show reduced body fat and increased mortality during early adulthood with an average life span of about 5 months. Mutant mice produce poorly nutritional milk and are unable to nourish their litters leading in high pre-weaning mortality.|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||The role in phosphatidylglycerols remodeling and cardiolipin synthesis is questioned as both processes occur in mitochondria. The monoacylglycerol acyltransferase activity is also weak and a direct role in triacylglycerol synthesis appears unlikely.|||Ubiquitous. Expressed in heart, kidney, liver, skin, intestine, and thymus. Highest expression is detected in brain and testis. http://togogenome.org/gene/10090:Psma4 ^@ http://purl.uniprot.org/uniprot/Q9R1P0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1A family.|||Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).|||Cytoplasm|||Detected in liver (at protein level).|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:16857966, PubMed:22341445). http://togogenome.org/gene/10090:Fus ^@ http://purl.uniprot.org/uniprot/P56959|||http://purl.uniprot.org/uniprot/Q3USY4|||http://purl.uniprot.org/uniprot/Q564D0|||http://purl.uniprot.org/uniprot/Q8CFQ9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM TET family.|||DNA/RNA-binding protein that plays a role in various cellular processes such as transcription regulation, RNA splicing, RNA transport, DNA repair and damage response. Binds to nascent pre-mRNAs and acts as a molecular mediator between RNA polymerase II and U1 small nuclear ribonucleoprotein thereby coupling transcription and splicing. Binds also its own pre-mRNA and autoregulates its expression; this autoregulation mechanism is mediated by non-sense-mediated decay. Plays a role in DNA repair mechanisms by promoting D-loop formation and homologous recombination during DNA double-strand break repair (By similarity). In neuronal cells, plays crucial roles in dendritic spine formation and stability, RNA transport, mRNA stability and synaptic homeostasis (PubMed:16317045, PubMed:25968143).|||Nucleus|||Phosphorylated in its N-terminal serine residues upon induced DNA damage. ATM and DNA-PK are able to phosphorylate FUS N-terminal region.|||Self-oligomerizes (via N-terminal region). Oligomerization is essential for chromatin binding. Component of nuclear riboprotein complexes. Interacts with ILF3, TDRD3 and SF1. Interacts through its C-terminus with SFRS13A. Interacts with OTUB1 and SARNP. Interacts with LRSAM1. Interacts with SAFB1 in a DNA-dependent manner; this interaction tethers FUS to chromatin. Interacts with MATR3. Interacts with SNRNP70 and POLR2A; these interactions couple RNA transcription and splicing. Interacts (through its RNA-binding domain) with RALY (through its RNA-binding domain); both are components of the same RNPs. http://togogenome.org/gene/10090:Poglut2 ^@ http://purl.uniprot.org/uniprot/Q9JHP7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the KDELC family.|||Endoplasmic reticulum lumen|||Expressed in various fetal tissues.|||N-glycosylated.|||Protein glucosyltransferase that catalyzes the transfer of glucose from UDP-glucose to a serine residue within the consensus sequence peptide C-X-N-T-X-G-S-F-X-C. Can also catalyze the transfer of xylose from UDP-xylose but less efficiently. Specifically targets extracellular EGF repeats of proteins such as NOTCH1, NOTCH3, FBN1, FBN2 and LTBP1. May regulate the transport of NOTCH1 and NOTCH3 to the plasma membrane and thereby the Notch signaling pathway.|||Widely expressed. http://togogenome.org/gene/10090:Slc39a9 ^@ http://purl.uniprot.org/uniprot/Q8BFU1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ZIP transporter (TC 2.A.5) family.|||Cell membrane|||Mitochondrion|||Nucleus|||Transports zinc ions across cell and organelle membranes into the cytoplasm and regulates intracellular zinc homeostasis. Participates in the zinc ions efflux out of the secretory compartments. Regulates intracellular zinc level, resulting in the enhancement of AKT1 and MAPK3/MAPK1 (Erk1/2) phosphorylation in response to the BCR activation (By similarity). Also functions as membrane androgen receptor that mediates, through a G protein, the non-classical androgen signaling pathway, characterized by the activation of MAPK3/MAPK1 (Erk1/2) and transcription factors CREB1 or ATF1 (PubMed:26208885). This pathway contributes to CLDN1 and CLDN5 expression and tight junction formation between adjacent Sertoli cells (By similarity). Mediates androgen-induced vascular endothelial cell proliferation through activation of an inhibitory G protein leading to the AKT1 and MAPK3/MAPK1 (Erk1/2) activation which in turn modulate inhibition (phosphorylation) of GSK3B and CCND1 transcription. Moreover, has dual functions as membrane-bound androgen receptor and as an androgen-dependent zinc transporter both of which are mediated through an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling leading to the androgen-dependent apoptotic process (By similarity).|||perinuclear region|||trans-Golgi network membrane http://togogenome.org/gene/10090:Bex1 ^@ http://purl.uniprot.org/uniprot/Q9R224 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BEX family.|||Cytoplasm|||Down-regulated following RA treatment. Up-regulated in parthenogenetic embryos.|||Interacts with neurotrophin receptor p75NTR/NGFR (By similarity). Interacts with OMP (PubMed:12054873, PubMed:12911636, PubMed:15198671).|||Nucleus|||Phosphorylated. Phosphorylation of Ser-105 protects it from the proteasome.|||Primarily localized to neuronal cells within several regions of the brain, including the olfactory epithelium, bulb, peri/paraventricular nuclei, suprachiasmatic nucleus, arcuate nucleus, median eminence, lateral hypothalamic area, thalamus, hippocampus and cerebellum (at protein level). Expressed in brain, mid term embryos and to a lesser extent in ovary. In testis, it is expressed in the pachytene spermatocytes and spermatids but not in spermatogonia.|||Signaling adapter molecule involved in p75NTR/NGFR signaling (By similarity). Plays a role in cell cycle progression and neuronal differentiation (By similarity). Inhibits neuronal differentiation in response to nerve growth factor (NGF) (By similarity). May act as a link between the cell cycle and neurotrophic factor signaling, possibly by functioning as an upstream modulator of receptor signaling, coordinating biological responses to external signals with internal cellular states (By similarity). In absence of reductive stress, acts as a pseudosubstrate for the CRL2(FEM1B) complex: associates with FEM1B via zinc, thereby preventing association between FEM1B and its substrates (PubMed:34562363).|||The histidine cluster (His cluster) and Cys-125 mediate zinc-binding.|||Ubiquitinated. Degraded by the proteasome. http://togogenome.org/gene/10090:Ly6c2 ^@ http://purl.uniprot.org/uniprot/P0CW03 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Ipo9 ^@ http://purl.uniprot.org/uniprot/E9QKZ2 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Arfip1 ^@ http://purl.uniprot.org/uniprot/G5E8V9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Forms homodimers or heterodimers with ARFIP2. Interacts with non-myristoylated GTP-bound ARF3, but not to GDP-bound ARF3. Interacts with ARF1. Binds with lower affinity to ARF5 and with very little affinity to ARF6. Interacts with ARL1. Interacts with ATG9A.|||Golgi apparatus|||Phosphorylated by PRKD1; phosphorylation delocalizes ARFIP1 from the Golgi and disrupts its ability to inhibit the activity of ADP-ribosylation factor, an important component of the vesicle scission machinery.|||Plays a role in controlling biogenesis of secretory granules at the trans-Golgi network. Mechanistically, binds ARF-GTP at the neck of a growing secretory granule precursor and forms a protective scaffold. Once the granule precursor has been completely loaded, active PRKD1 phosphorylates ARFIP1 and releases it from ARFs. In turn, ARFs induce fission. Through this mechanism, ensures proper secretory granule formation at the Golgi of pancreatic beta cells.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Spp1 ^@ http://purl.uniprot.org/uniprot/F8WIP8|||http://purl.uniprot.org/uniprot/P10923|||http://purl.uniprot.org/uniprot/Q3UBR1|||http://purl.uniprot.org/uniprot/Q547B5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity.|||Belongs to the osteopontin family.|||Extensively phosphorylated by FAM20C in the extracellular medium at multiple sites within the S-x-E/pS motif (By similarity). The phosphorylated form inhibits hydroxyapatite crystallization (PubMed:23427088). Dephosphorylation via a mechanism involving ALPL/TNAP promotes hydroxyapatite crystallization (PubMed:23427088).|||Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers, increasing its collagen binding properties.|||Ligand for integrin alpha-V/beta-3.|||Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.|||O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Rbm15b ^@ http://purl.uniprot.org/uniprot/Q6PHZ5 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Aberrant splicing.|||Belongs to the RRM Spen family.|||Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B). May interact with NCOR2. Interacts with NXF1, the interaction is required to promote mRNA export.|||Nucleus envelope|||Nucleus speckle|||RNA-binding protein that acts as a key regulator of N6-methyladenosine (m6A) methylation of RNAs, thereby regulating different processes, such as alternative splicing of mRNAs and X chromosome inactivation mediated by Xist RNA. Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Plays a key role in m6A methylation, possibly by binding target RNAs and recruiting the WMM complex. Involved in random X inactivation mediated by Xist RNA: acts by binding Xist RNA and recruiting the WMM complex, which mediates m6A methylation, leading to target YTHDC1 reader on Xist RNA and promoting transcription repression activity of Xist. Functions in the regulation of alternative or illicit splicing, possibly by regulating m6A methylation. Inhibits pre-mRNA splicing. Also functions as a mRNA export factor by acting as a cofactor for the nuclear export receptor NXF1.|||nucleoplasm http://togogenome.org/gene/10090:Mgam ^@ http://purl.uniprot.org/uniprot/A0A571BF69|||http://purl.uniprot.org/uniprot/B5THE2 ^@ Caution|||Similarity ^@ Belongs to the glycosyl hydrolase 31 family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Il11ra2 ^@ http://purl.uniprot.org/uniprot/P70225 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 3 subfamily.|||Expression restricted to testis, lymph node and thymus. Highest level in testis.|||Il11ra2 appears to arise through gene duplication of ancestral origin and has been lost in some inbred mouse strains.|||Membrane|||On ligand binding, forms a multimer complex with IL6ST/gp130.|||Receptor for interleukin-11. The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells. http://togogenome.org/gene/10090:Prss42 ^@ http://purl.uniprot.org/uniprot/Q8VIF2 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Cytoplasm|||In testis, expressed at all stages from the late pachytene primary spermatocyte to the secondary spermatocyte. Not detected at day 7 after birth. Expression is detected at day 14 and increases dramatically at day 21 and reach a peak at day 28 to remain high until day 56.|||Lacks protease activity in vitro.|||Plays a role in spermatogenesis. Involved in germ cell survival during meiosis. Lacks protease activity in vitro.|||Testis-specific (PubMed:23536369). Mainly detected in round spermatids at all the eminiferous epithelial stages (at protein level) (PubMed:23536369). http://togogenome.org/gene/10090:Cdc42ep2 ^@ http://purl.uniprot.org/uniprot/Q8JZX9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BORG/CEP family.|||Endomembrane system|||Interacts with CDC42 and RHOQ in a GTP-dependent manner, and with SEPT7.|||Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts in a CDC42-dependent manner (By similarity).|||The CRIB domain mediates interaction with CDC42.|||cytoskeleton http://togogenome.org/gene/10090:Wtip ^@ http://purl.uniprot.org/uniprot/Q7TQJ8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates Hippo signaling pathway and antagonizes phosphorylation of YAP1. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. In podocytes, may play a role in the regulation of actin dynamics and/or foot process cytoarchitecture. In the course of podocyte injury, shuttles into the nucleus and acts as a transcription regulator that represses WT1-dependent transcription regulation, thereby translating changes in slit diaphragm structure into altered gene expression and a less differentiated phenotype. Involved in the organization of the basal body (By similarity). Involved in cilia growth and positioning (By similarity).|||Belongs to the zyxin/ajuba family.|||Cell membrane|||Expressed in kidney, lung, eye and ovary. In kidney, restricted to podocytes.|||Forms homodimers. Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM domains) with VHL (By similarity). Interacts with CD2AP and WT1. Interacts (via LIM domains) with SNAI1 (via SNAG domain), SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain). Interacts with ROR2. Following treatment with bacterial lipopolysaccharide (LPS), forms a complex with MAPK8IP3 and dynein intermediate chain. Interacts with PRICKLE3 (By similarity).|||From 9.5 to 11.5 dpc, expressed in the branchial arches, otic vesicle, limb buds, somites, craniofacial mesenchyme and tail buds. At 14.5 dpc, expressed in the developing tongue, nasal cavity, palate, adrenal gland, in the forebrain, dorsal root ganglia and in the somites. At 14.5 dpc, also detected in lung, rib cartilage, kidney and intestine (at protein level). In the kidney, expression peaks at 15 to 16 dpc and decreases thereafter, but persists in adulthood.|||Nucleus|||adherens junction|||cytosol|||focal adhesion http://togogenome.org/gene/10090:Rrn3 ^@ http://purl.uniprot.org/uniprot/B2RS91 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRN3 family.|||Interacts with TAF1B. Interacts with POLR1F, EIF3L and TAF1C (By similarity).|||Phosphorylated at Thr-198 by MAPK9/JNK2, which abrogates initiation complex formation.|||Required for efficient transcription initiation by RNA polymerase I. Required for the formation of the competent preinitiation complex (PIC). Dissociates from pol I as a consequence of transcription. In vitro, cannot activate transcription in a subsequent transcription reaction.|||nucleolus http://togogenome.org/gene/10090:Cdh2 ^@ http://purl.uniprot.org/uniprot/P15116|||http://purl.uniprot.org/uniprot/Q3UIC2|||http://purl.uniprot.org/uniprot/Q8BSI9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins.|||Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell (PubMed:2762814, PubMed:11433297, PubMed:17988630, PubMed:9655503, PubMed:25253890). Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence (PubMed:24952463). Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells (PubMed:26750727). Required for proper neurite branching. Required for pre- and postsynaptic organization (By similarity). CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density.|||Cell junction|||Cell membrane|||Cell surface|||Cleaved by MMP24 (PubMed:19805319, PubMed:24952463). Ectodomain cleavage leads to the generation of a soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa (PubMed:24952463). Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence (PubMed:24952463).|||Embryonic lethality.|||Expressed at all stages of testicular development with the highest expression levels found in testes of 21-day-old mice (PubMed:8879495). Expressed at the outer limiting membrane of the retina at 3 months of age (PubMed:23001562). Expression is restricted to the lens stalk region between 10 and 11 dpc. At later stages (17.5 dpc), it is expressed in the developing lens and corneal endothelium (PubMed:31650526).|||Expressed in cardiac muscle (at protein level).|||Homodimer (via extracellular region) (PubMed:21300292, PubMed:25253890). Can also form heterodimers with other cadherins (via extracellular region) (PubMed:25253890). Dimerization occurs in trans, i.e. with a cadherin chain from another cell (PubMed:21300292, PubMed:25253890). Interacts with CDCP1 (By similarity). Interacts with PCDH8; this complex may also include TAOK2 (By similarity). The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway (By similarity). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297). May interact with OBSCN (via protein kinase domain 2) (PubMed:23392350). Interacts with FBXO45 (By similarity).|||May be phosphorylated by OBSCN.|||Membrane|||O-glycosylated on Ser and Thr residues.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.|||adherens junction|||desmosome|||sarcolemma http://togogenome.org/gene/10090:Or5b109 ^@ http://purl.uniprot.org/uniprot/Q7TQR3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sln ^@ http://purl.uniprot.org/uniprot/Q9CQD6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sarcolipin family.|||Endoplasmic reticulum membrane|||Highly expressed in heart atrium, red gastrocnemius muscle and soleus. Detected at lower levels in the extensor digitorum longus muscle (at protein level).|||Interacts with calcium ATPase ATP2A1/SERCA1. Interact with ATP2A2; the inhibition decreases ATP2A1 Ca(2+) affinity. Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2 (By similarity).|||No visible phenotype at 22 degrees Celsius. Increased heat-loss and failure to maintain body temperature at 4 degrees Celsius when the shivering response is prevented. Mice show increased weight gain and obesity when kept on a high-fat diet. Mice display faster muscle relaxation rates in soleus due to an increase in the affinity of ATP2A1 for Ca(2+).|||Reversibly inhibits the activity of ATP2A1 and ATP2A2 in sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in muscle (PubMed:21697544, PubMed:26816378). Required for muscle-based, non-shivering thermogenesis (PubMed:22961106).|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Wdr77 ^@ http://purl.uniprot.org/uniprot/Q99J09 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the methylosome complex composed of PRMT5, WDR77 and CLNS1A (By similarity). Found in a complex composed of PRMT5, WDR77 and RIOK1 (By similarity). RIOK1 and CLNS1A bound directly to PRMT5 at the same binding site, in a mutually exclusive manner, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively (By similarity). Found in a complex with the component of the methylosome, PRMT5, CLNS1A, WDR77, PRMT1 and ERH (By similarity). Directly interacts with PRMT5, as well as with several Sm proteins, including SNRPB and SNRPD2 and, more weakly, SNRPD3 and SNRPE (By similarity). Forms a compact hetero-octamer with PRMT5, decorating the outer surface of a PRMT5 tetramer (By similarity). Interacts with SUZ12 and histone H2A/H2AC20, but not with histones H2B, H3 nor H4 (PubMed:16712789). Interacts with CTDP1 and LSM11 (By similarity). Interacts with APEX1, AR and NKX3-1 (By similarity). Interacts with CHTOP (By similarity). Interacts with FAM47E (By similarity). Component of the DCX(WDR77) complex, composed of Cul4b, Ddb1, Wdr77 and Rbx1 (PubMed:35197566). Interacts with TSC22D2 (By similarity).|||Cytoplasm|||Non-catalytic component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones (By similarity). This modification targets Sm proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein core particles (By similarity). Might play a role in transcription regulation (By similarity). The methylosome complex also methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (PubMed:19584108).|||Nucleus|||Substrate-recognition component of the DCX(WDR77) complex, which mediates ubiquitination and degradation of Irgm1 in intestinal cells. http://togogenome.org/gene/10090:Sstr1 ^@ http://purl.uniprot.org/uniprot/P30873|||http://purl.uniprot.org/uniprot/Q543T0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Jejunum and stomach.|||Membrane|||Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins. http://togogenome.org/gene/10090:Serpinb9g ^@ http://purl.uniprot.org/uniprot/Q8VHQ1|||http://purl.uniprot.org/uniprot/Q9DAZ7 ^@ Similarity ^@ Belongs to the serpin family. Ov-serpin subfamily. http://togogenome.org/gene/10090:Pebp4 ^@ http://purl.uniprot.org/uniprot/Q9D9G2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the phosphatidylethanolamine-binding protein family.|||Promotes AKT phosphorylation, suggesting a possible role in the PI3K-AKT signaling pathway.|||Secreted http://togogenome.org/gene/10090:Pdlim4 ^@ http://purl.uniprot.org/uniprot/P70271 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Early endosome membrane|||Expressed in several non-muscle tissues including lung, brain, ovary and uterus, and especially in epithelial cells at 14 dpc. In the uterus, high expression in the glandular epithelium, but absent in the simple columnar epithelium lining the uterus cavity.|||Homodimer (By similarity). Interacts (via C-terminus only or via combined C-terminus and LIM domain, but not LIM domain only) with PTPN13 (via the second or fourth PDZ domains) (PubMed:9487134, PubMed:15663004). Found in a complex with PTPN13 and TRIP6 (PubMed:10826496). Interacts (via PDZ domain) with ACTN1 and ACTN2 (via C-terminal SDL residues) (By similarity). Interacts (via PDZ domain) with TRIP6 (via the second LIM domain or via the third LIM domain plus C-terminus) (PubMed:10826496). Interacts (via LIM domain) with GRIA1 (via C-terminus); this interaction as well as the interaction with alpha-actinin is required for their colocalization in early endosomes. Interacts with PDLIM1 (By similarity). Forms (via LIM domain) a heterodimer with PDLIM3 (PubMed:15663004). Interacts directly with SRC (via kinase domain and to a lesser extent the SH2 domain) (By similarity).|||Nucleus|||Phosphorylated on tyrosine residue(s). Can be dephosphorylated by PTPN13.|||Recycling endosome membrane|||Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle. Involved in reorganization of the actin cytoskeleton (By similarity). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity).|||cytoskeleton|||dendritic spine|||lamellipodium|||perinuclear region|||synaptosome http://togogenome.org/gene/10090:Pbld1 ^@ http://purl.uniprot.org/uniprot/Q9DCG6 ^@ Similarity ^@ Belongs to the PhzF family. http://togogenome.org/gene/10090:Cd40lg ^@ http://purl.uniprot.org/uniprot/P27548|||http://purl.uniprot.org/uniprot/Q0VEI3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which have cell-type dependent effects, such as B-cell activation, NF-kappa-B signaling and anti-apoptotic signaling.|||Belongs to the tumor necrosis factor family.|||Cell membrane|||Cell surface|||Cytokine that acts as a ligand to CD40/TNFRSF5 (By similarity). Costimulates T-cell proliferation and cytokine production (By similarity). Its cross-linking on T-cells generates a costimulatory signal which enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation (By similarity). Induces the activation of NF-kappa-B (By similarity). Induces the activation of kinases MAPK8 and PAK2 in T-cells (By similarity). Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4 (PubMed:1374165). Involved in immunoglobulin class switching (PubMed:1374165).|||Cytokine that acts as a ligand to CD40/TNFRSF5. Costimulates T-cell proliferation and cytokine production. Involved in immunoglobulin class switching.|||Homotrimer (PubMed:8095800). Interacts with CD28 (By similarity). CD40 ligand, soluble form: Exists as either a monomer or a homotrimer (By similarity). Forms a ternary complex between CD40 and integrins for CD40-CD40LG signaling (By similarity).|||Homotrimer.|||Secreted|||Specifically expressed on activated CD4+ T-lymphocytes.|||The soluble form derives from the membrane form by proteolytic processing. http://togogenome.org/gene/10090:Gm21660 ^@ http://purl.uniprot.org/uniprot/J3QP49 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or13ae2 ^@ http://purl.uniprot.org/uniprot/Q8VF43 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or4p22 ^@ http://purl.uniprot.org/uniprot/Q8VG86 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stag3 ^@ http://purl.uniprot.org/uniprot/O70576 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SCC3 family.|||Chromosome|||Component of the meiosis-specific cohesin complex, which also contains the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer. Such complex likely contains RAD21, or the meiosis-specific related protein REC8 (By similarity). Interacts with CCDC79/TERB1; recruiting cohesin to telomeres to develop structural rigidity.|||Deficient mice are sterile and their fetal oocytes are arrested at early prophase I leading to oocyte depletion at 1 week of age.|||Meiosis specific component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I.|||Nucleus|||Phosphorylated.|||Testis specific.|||centromere http://togogenome.org/gene/10090:Abcc12 ^@ http://purl.uniprot.org/uniprot/Q80WJ6 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Does not transport any of the organic anions transported by the other multidrug resistance-associated proteins (MRPs) in vesicular transport assays, nor does it confer resistance to cytotoxic agents in intact cell assays.|||Endoplasmic reticulum membrane|||First detected at 3 weeks of age IN the pachytene spermatocytes. During germ cell differentiation in the adult testis, pachytene spermatocytes in stage VI of the epithelial cycle are the first germ cells to show MRP9 expression.|||Probable transporter, its substrate specificity is unknown.|||Widely expressed at low level (PubMed:12801629, PubMed:16141072, PubMed:17472575). Highly expressed in testis by Sertoli cells and Leydig cells (PubMed:12801629, PubMed:16141072). Detected in testicular germ cells and sperm (at protein level) (PubMed:17472575). http://togogenome.org/gene/10090:Klhl40 ^@ http://purl.uniprot.org/uniprot/Q9D783 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A band|||Absent early during embryogenesis (7 dpc), present at the middle stage (11 dpc) and highly expressed at the later stages (15 dpc and 17 dpc) (PubMed:24361185). Specifically expressed in the somites at 11.5 dpc and in the skeletal muscle at 15.5 dpc (PubMed:24361185).|||Belongs to the KLHL40 family.|||Component of the BCR(KLHL40) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL40 and RBX1 (PubMed:24361185). Interacts with LMOD3 (PubMed:24960163).|||Cytoplasm|||I band|||Neonates are normal in size at birth and were born with the expected Mendelian ratio (PubMed:24960163, PubMed:25940086). They however fail to gain weight and do not survive to weaning (PubMed:24960163, PubMed:25940086). Defects are due to smaller muscle fibers and a disorganized sarcomeric structure (PubMed:24960163, PubMed:25940086).|||Specifically expressed in skeletal muscles in embryonic, neonatal and adults (PubMed:24960163, PubMed:25940086). Expressed in various types of muscles, including extensor digitorum longus, gastrocnemius, soleus, diaphragm, masseter and heart (at protein level). Not detected in brain, liver and lung (at protein level).|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:25940086). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (PubMed:25940086). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (PubMed:24960163).|||Up-regulated during myogenic differentiation (PubMed:24361185). Induced during the differentiation of myoblasts into myotubes (PubMed:23746549). http://togogenome.org/gene/10090:Or4p23 ^@ http://purl.uniprot.org/uniprot/Q7TR12 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdhga11 ^@ http://purl.uniprot.org/uniprot/Q91XY8 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Clic6 ^@ http://purl.uniprot.org/uniprot/Q8BHB9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the chloride channel CLIC family.|||Cell membrane|||Cytoplasm|||Interacts with dopamine receptors DRD2, DRD3 and DRD4.|||May insert into membranes and form chloride ion channels. May play a critical role in water-secreting cells, possibly through the regulation of chloride ion transport (By similarity).|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity).|||Phosphorylated. http://togogenome.org/gene/10090:Fbxo44 ^@ http://purl.uniprot.org/uniprot/Q8BK26 ^@ Developmental Stage|||Function|||Subunit|||Tissue Specificity ^@ Expressed in brain, liver, pancreas and adipose tissue (at protein level). Widely expressed.|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with SKP1 and CUL1 (By similarity).|||Strong expression in embryos. Maximally expressed in brain during embryonic development but declined thereafter.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Eif3f ^@ http://purl.uniprot.org/uniprot/Q3U8X1|||http://purl.uniprot.org/uniprot/Q3UVY8|||http://purl.uniprot.org/uniprot/Q9DCH4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit F family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with RNF139; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner. Interacts with DTX1, the interaction is required for deubiquitinating activity towards NOTCH1 (By similarity).|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm|||Deubiquitinates activated NOTCH1, promoting its nuclear import, thereby acting as a positive regulator of Notch signaling.|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation.|||Phosphorylation is enhanced upon serum stimulation. Phosphorylated during apoptosis by caspase-processed CDK11 (By similarity).|||The MPN domain mediates deubiquitinating activity. http://togogenome.org/gene/10090:Tex29 ^@ http://purl.uniprot.org/uniprot/Q9DA77 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Boc ^@ http://purl.uniprot.org/uniprot/Q6AZB0 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells.|||Highly expressed in embryonic somites, limb buds, dermomyotomes and in the neural tube.|||Membrane|||Part of a complex that contains BOC, CDON, NEO1, cadherins and CTNNB1. Interacts with SHH, DHH and IHH. Interacts with NTN3 (By similarity). Interacts with CDH2 and CTNNB1. Interacts with CDH15 only during the early stages of myoblast differentiation.|||Up-regulated during early stages of myoblast differentiation. http://togogenome.org/gene/10090:Trim27 ^@ http://purl.uniprot.org/uniprot/Q62158 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates and thereby plays a role in diffent processes including proliferation, innate immunity, apoptosis, immune response or autophagy (PubMed:24144979). Ubiquitinates PIK3C2B and inhibits its activity by mediating the formation of 'Lys-48'-linked polyubiquitin chains; the function inhibits CD4 T-cell activation (By similarity). Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, leading to promote endosomal F-actin assembly (By similarity). Has a transcriptional repressor activity by cooperating with EPC1 (By similarity). Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events (By similarity). May function in male germ cell development (By similarity). Has DNA-binding activity and preferentially bound to double-stranded DNA (By similarity). Forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which in turn deubiquitinates RIPK1 resulting in the positive regulation of TNF-alpha-induced apoptosis (PubMed:24144979). In addition, acts with USP7 or PTPN11 as an inhibitor of the antiviral signaling pathway by promoting kinase TBK1 ubiquitination and degradation (By similarity). Acts as a negative regulator of NOD2 signaling by mediating ubiquitination of NOD2, promoting its degradation by the proteasome (By similarity). Alternatively, facilitates mitophagy via TBK1 activation (By similarity). Negatively regulates autophagy flux under basal conditions by directly polyubiquitinating ULK1 (By similarity). During starvation-induced autophagy, catalyzes non-degradative ubiquitination of the kinase STK38L promoting its activation and phosphorylation of ULK1 leading to its ubiquitination and degradation to restrain the amplitude and duration of autophagy (By similarity).|||Early endosome|||Homomultimerizes. Part of a complex consisting of TRIM27, USP7 and MAGEL2; directly interacts with USP7. Interacts with PML, EIF3S6, EPC1, CHD4 and EID1. Interacts with MAGED4, MAGEF1 and MAGEL2. Interacts with PTPN11. Interacts with autophagy receptor p62/SQSTM1.|||Mitochondrion|||Nucleus|||PML body|||TRIM27-deficient mice are resistant to TNF-alpha-induced apoptosis.|||The coiled-coil region mediates interaction with EPC1 and CHD4. The B box and coiled-coil domains mediate interaction with PML. The B box and the distal coiled-coil domains mediate homomultimerisation. The B30.2 domain mediates interaction with EIF3S6.|||Widely expressed. High expression is detected in testis. Low levels were detected in spleen, thymus, cerebrum and cerebellum. http://togogenome.org/gene/10090:Ccdc61 ^@ http://purl.uniprot.org/uniprot/Q3UJV1 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC61 family.|||Forms homodimers (via head domain) (By similarity). Interacts with CEP170 (By similarity). Interacts with PCM1 and CEP131 (By similarity). Binds tubulin (By similarity).|||Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker. In interphase, required for anchoring microtubule at the mother centriole subdistal appendages and for centrosome positioning. During mitosis, may be involved in spindle assembly and chromatin alignment by regulating the organization of spindle microtubules into a symmetrical structure. Plays a non-essential role in ciliogenesis.|||The N-terminal 3D structure (head domain) resembles that of NHEJ1/XLF, PAXX, SASS6 and XRCC4.|||The coiled-coil domains are involved in microtubule-binding.|||centriolar satellite|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Nt5c2 ^@ http://purl.uniprot.org/uniprot/A0A494B9X3|||http://purl.uniprot.org/uniprot/E9Q9M1|||http://purl.uniprot.org/uniprot/Q3V1L4 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate. Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding. Inhibited by inorganic phosphate.|||Belongs to the 5'(3')-deoxyribonucleotidase family.|||Binds 1 Mg(2+) ion per subunit.|||Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates. In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine. Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP. Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency. Through these activities regulates the purine nucleoside/nucleotide pools within the cell.|||Homotetramer.|||cytosol http://togogenome.org/gene/10090:Chac2 ^@ http://purl.uniprot.org/uniprot/Q9CQG1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.|||Catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide (PubMed:27913623). Acts specifically on glutathione, but not on other gamma-glutamyl peptides (By similarity).|||Monomer.|||cytosol http://togogenome.org/gene/10090:Sub1 ^@ http://purl.uniprot.org/uniprot/P11031 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is controlled by protein kinases that target the regulatory region. Phosphorylation inactivates both ds DNA-binding and cofactor function, but does not affect binding to ssDNA (By similarity).|||Belongs to the transcriptional coactivator PC4 family.|||General coactivator that functions cooperatively with TAFs and mediates functional interactions between upstream activators and the general transcriptional machinery. May be involved in stabilizing the multiprotein transcription complex. Binds single-stranded DNA. Also binds, in vitro, non-specifically to double-stranded DNA (ds DNA).|||Homodimer. Interacts with CSTF2 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Dync1i1 ^@ http://purl.uniprot.org/uniprot/D6Q0F3|||http://purl.uniprot.org/uniprot/D6Q0F4|||http://purl.uniprot.org/uniprot/O88485|||http://purl.uniprot.org/uniprot/Q3TYJ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1. May play a role in mediating the interaction of cytoplasmic dynein with membranous organelles and kinetochores.|||Belongs to the dynein intermediate chain family.|||Cytoplasm|||Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1H1. Interacts with DYNLT1 and DYNLT3. Interacts with DCTN1 (By similarity). Interacts with DYNLL2.|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Smg8 ^@ http://purl.uniprot.org/uniprot/Q8VE18 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the SMG8 family.|||Component of the SMG1C complex composed of SMG1, SMG8 and SMG9; the recruitment of SMG8 to SMG1 N-terminus induces a large conformational change in the SMG1 C-terminal head domain containing the catalytic domain. Forms heterodimers with SMG9; this assembly form may represent a SMG1C intermediate form (By similarity).|||Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG9 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required to mediate the recruitment of SMG1 to the ribosome:SURF complex and to suppress SMG1 kinase activity until the ribosome:SURF complex locates the exon junction complex (EJC). Acts as a regulator of kinase activity (By similarity).|||Phosphorylated by SMG1. http://togogenome.org/gene/10090:Trim66 ^@ http://purl.uniprot.org/uniprot/Q924W6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can form homodimers and heterodimers. Interacts with CBX5, CBX1 and CBX3 via PxVxL motif.|||May function as transcription repressor; The repressive effects are mediated, at least in part, by recruitment of deacetylase activity. May play a role as negative regulator of postmeiotic genes acting through CBX3 complex formation and centromere association.|||No significant expression in testis of 2- or 3-week-old mouse, but clear detection at the age of 4 weeks.|||Nucleus|||Predominant in testis, specifically in elongating spermatids. http://togogenome.org/gene/10090:Cbl ^@ http://purl.uniprot.org/uniprot/A0A0X1KG61|||http://purl.uniprot.org/uniprot/P22682 ^@ Disease Annotation|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Ubiquitinates SPRY2 (By similarity). Ubiquitinates EGFR (By similarity). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-737' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3 (PubMed:10393178, PubMed:12649282, PubMed:19265199, PubMed:20100865, PubMed:9653117). In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (PubMed:29237719).|||Can be converted to an oncogenic protein by deletions or mutations that disturb its ability to down-regulate RTKs.|||Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.|||Forms homodimers; IFT20 promotes the formation of stable homodimers (By similarity). Interacts (phosphorylated) with PIK3R1. Interacts with phosphorylated LAT2 (By similarity). Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Interacts with FGR. Also interacts with BLK, SORBS1 and INPPL1/SHIP2. Interacts with CBLB. Interacts with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with ALK, AXL and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with ATX2 (PubMed:18602463). Interacts with SH3KBP1 and this interaction is inhibited in the presence of SHKBP1 (PubMed:21830225). Interacts with SIGLEC10 (PubMed:23374343). Interacts with IFT20 (By similarity). Interacts with SPRY2; the interaction inhibits CBL-mediated ubiquitination of EGFR (By similarity). Interacts (phosphorylated at Tyr-780) with tensin TNS4 (via SH2 domain); the interaction is enhanced in the presence of EGF and reduces interaction of CBL with EGFR (By similarity). Interacts with EGFR; the interaction is reduced in the presence of TNS4 (By similarity).|||Golgi apparatus|||Phosphorylated on tyrosine residues by ALK, EGFR, FGR, INSR, SYK, FYN and ZAP70. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Phosphorylated on tyrosine residues by activated PDGFRA and PDGFRB (By similarity). Phosphorylated on tyrosine residues in response to CSF1R, FLT1 and KIT signaling. Phosphorylated on tyrosine residues by HCK.|||The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.|||The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.|||This protein has one functional calcium-binding site.|||Ubiquitinated, leading to its degradation via the proteasome. Ubiquitination is negatively regulated by IFT20.|||cilium http://togogenome.org/gene/10090:Vmn1r217 ^@ http://purl.uniprot.org/uniprot/Q8R270 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Creb3l2 ^@ http://purl.uniprot.org/uniprot/Q8BH52 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. ATF subfamily.|||Binds DNA as a dimer.|||Endoplasmic reticulum membrane|||Mutant mice are born at the expected Mendelian rate, but die by suffocation shortly after birth because of an immature chest cavity. They exhibit severe chondrodysplasia. The cartilage shows a lack of typical columnar structure in the proliferating zone and a decrease in the size of the hypertrophic zone, resulting in a significant reduction of extracellular matrix proteins. Proliferating chondrocytes show abnormally expanded ER, containing aggregated type II collagen and cartilage oligomeric matrix protein (COMP). Displays significant decrease in Sec23a levels.|||N-glycosylated.|||Nucleus|||Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (PubMed:19767744). In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827).|||Ubiquitinated by HRD1/SYVN1; undergoes 'Lys-48'-linked ubiquitination, followed by rapid proteasomal degradation under normal conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase dissociates from its substrate, ubiquitination does not occur and CREB3L2 is stabilized.|||Up-regulated by ER stress at the transcript and protein levels, the increase at the protein level is much higher than at the transcript level. This induction is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain. Up-regulated in brain areas undergoing ischemic injury, in neurons, but not astrocytes. Up-regulated by SOX9 during chondrocyte differentiation, possibly through SOX9-induced mild ER stress (PubMed:19767744).|||Upon ER stress, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain. The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2).|||Widely expressed, including in lung, bladder, ovary, testis and spleen (PubMed:17178827). Highly expressed in chondrocytes (PubMed:19767744). http://togogenome.org/gene/10090:Or12e9 ^@ http://purl.uniprot.org/uniprot/L7MTT1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sprr2a3 ^@ http://purl.uniprot.org/uniprot/Q4KL71|||http://purl.uniprot.org/uniprot/Q9CQK8 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cornifin (SPRR) family.|||By type-2 cytokines IL4 and IL13 in response to helminth infection.|||Forms five pairs of intrachain disulfide bonds.|||Gut bactericidal protein that selectively kills Gram-positive bacteria by binding to negatively charged lipids on bacterial membranes, leading to bacterial membrane permeabilization and disruption (PubMed:34735226). Specifically binds lipids bearing negatively charged headgroups, such as phosphatidic acid, phosphatidylserine (PS), cardiolipin (CL), and phosphatidylinositol phosphates, but not to zwitterionic or neutral lipids (By similarity). Induced by type-2 cytokines in response to helminth infection and is required to protect against helminth-induced bacterial invasion of intestinal tissue (PubMed:34735226). May also be involved in the development of the cornified envelope of squamous epithelia; however, additional evidences are required to confirm this result in vivo (By similarity).|||Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an expansion of Gram-positive bacteria in the small intestinal lumen and mucus layer (PubMed:34735226). Mice were born in normal Mendelian ratios, are healthy and show normal intestinal morphology with no signs of inflammation in normal conditions (PubMed:34735226). They however show an increased abundance of Gram-positive bacteria in the small intestinal lumen, with a marked increase in the relative abundance of Lactobacillus, Turicibacter, and C.Arthromitus (PubMed:34735226). At the same time, a reduction in the abundance of Bacteroidetes, a class of Gram-negative bacteria is observed (PubMed:34735226). Mice are more susceptible to L. monocytogenes infection (PubMed:34735226).|||Mice lacking Sprr2a1, Sprr2a2 and Sprr2a3 show an expansion of Gram-positive bacteria in the small intestinal lumen and mucus layer (PubMed:34735226). Mice were born in normal Mendelian ratios, are healthy and show normal intestinal morphology with no signs of inflammation in normal conditions (PubMed:34735226). They however show an increased abundance of Gram-positive bacteria in the small intestinal lumen, with a marked increase in the relative abundance of Lactobacillus, Turicibacter, and C.arthromitus (PubMed:34735226). At the same time, a reduction in the abundance of Bacteroidetes, a class of Gram-negative bacteria is observed (PubMed:34735226). Mice are more susceptible to L. monocytogenes infection (PubMed:34735226).|||Secreted|||extracellular space|||secretory vesicle http://togogenome.org/gene/10090:Cd200r4 ^@ http://purl.uniprot.org/uniprot/H3BJX3|||http://purl.uniprot.org/uniprot/Q6XJV4 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to some authors (PubMed:15187158), CD200R4 is a receptor for the CD200/OX2 cell surface glycoprotein, but it was later found (PubMed:23602662) to miss key amino-acids for binding to CD200.|||Belongs to the CD200R family.|||Highly expressed in monocytes, NK cells and a subset of NKT cells. Weakly expressed in granulocytes and B-cells (at protein level). Expressed in brain, lung, testis, thymus, intestine and uterus. Expressed in bone marrow derived-macrophage and dendritic cells and mast cells.|||Interacts with TYROBP.|||Involved in the recruitment or surface expression of the TYROBP receptor.|||May be expressed in adult splenic cells (PubMed:15187158), as the antibody used could not discriminate between CD200R1 and CD200R4. May be expressed in uterus at 12.5 dpc (at protein level) (PubMed:15274657), as the antibody used could not discriminate between CD200R1 and CD200R4.|||Membrane http://togogenome.org/gene/10090:Ptch1 ^@ http://purl.uniprot.org/uniprot/Q61115 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Sonic hedgehog.|||Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis.|||Belongs to the patched family.|||Cell membrane|||Detected in cerebellar Bergmann glia cells (at protein level) (PubMed:24062445). In the developing embryo, first detected within the ventral neural tube and later in the somites and limb buds (PubMed:8595881). Expression in the limb buds is restricted to the posterior ectoderm surrounding the zone of polarizing activity (PubMed:8595881). In the adult, expression is seen in brain, lung, liver, kidney and ocular tissues; lower levels in heart, skeletal muscle, and testis (PubMed:8595881).|||Expressed at very low levels at 7 dpc, is most strongly expressed between 11 and 15 dpc, and persists at moderate levels at 17 dpc (PubMed:8595881). Also expressed in the adult (PubMed:8595881).|||Glycosylation is necessary for SHH binding.|||In the absence of Hh ligands, ubiquitination by ITCH at Lys-1413 promotes endocytosis and both proteasomal and lysosomal degradation.|||Interacts with SNX17 (By similarity). Interacts with IHH (PubMed:21537345). Interacts with G-protein coupled receptor GPR37L1 (PubMed:24062445). http://togogenome.org/gene/10090:Lxn ^@ http://purl.uniprot.org/uniprot/P70202|||http://purl.uniprot.org/uniprot/Q14BZ3 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protease inhibitor I47 (latexin) family.|||By CSF1 and lipopolysaccharides (LPS).|||Cytoplasm|||Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4 (By similarity). May play a role in inflammation.|||Highly enriched in macrophages. http://togogenome.org/gene/10090:Itgb1bp2 ^@ http://purl.uniprot.org/uniprot/Q9R000 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subunit|||Tissue Specificity ^@ Detectable in embryo limbs at day 15, reached a maximum in newborn, and declined in adult limb muscles. During heart development level remains steady from embryonic day 15 to adult stage.|||During muscle regeneration.|||Expressed in skeletal and cardiac muscles but not in other tissues. Is localized in rows flanking the Z line containing alpha-actinin.|||Interacts with beta-1 integrin subunit. This interaction is regulated by divalent cations, and it occurs only in absence of calcium.|||May play a role during maturation and/or organization of muscles cells.|||The tail domain binds to the cytoplasmic domain of both integrin beta-1a and beta-1d isoforms. The presence of Ca(2+) ions does not prevent binding of a fragment consisting of the second cysteine rich repeat and the tail domain but prevents the binding of the full-length protein. http://togogenome.org/gene/10090:Slc7a4 ^@ http://purl.uniprot.org/uniprot/Q8BLQ7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.|||Involved in the transport of the cationic amino acids (arginine, lysine and ornithine).|||Membrane http://togogenome.org/gene/10090:Or10u3 ^@ http://purl.uniprot.org/uniprot/Q7TS26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5h22 ^@ http://purl.uniprot.org/uniprot/K7N5T5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dap ^@ http://purl.uniprot.org/uniprot/Q91XC8 ^@ Function|||PTM|||Similarity|||Subunit ^@ Associates with ribosomes; inhibiting translation. Interacts with eiF5a (EIF5A and EIF5A2); inhibiting translation.|||Belongs to the DAP-DAPL1 family.|||Phosphorylated. Phosphorylation by MTOR inhibits the suppressive activity of DAP toward autophagy.|||Ribosome-binding protein involved in ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation. Acts via its association with eiF5a (EIF5A and EIF5A2) at the polypeptide exit tunnel of the ribosome, preventing mRNA translation. Involved in ribosome hibernation in the mature oocyte by preventing mRNA translation, leading to ribosome inactivation. Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo (By similarity). Also acts as a negative regulator of autophagy. Involved in mediating interferon-gamma-induced cell death (By similarity). http://togogenome.org/gene/10090:Sprr1a ^@ http://purl.uniprot.org/uniprot/Q62266 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane. May participate widely in the construction of cell envelopes in cornifying epithelia characterized by either increased thickness or a requirement for extreme flexibility.|||Cytoplasm|||Expressed in fetal periderm, hair follicles and in the thickened epidermis of the lip and footpad. Also present in the epithelia of various tissues such as the penis, vagina, forestomach, tongue and esophagus.|||First detected in fetal skin around day 16 and expression continues throughout newborn and adult stages. http://togogenome.org/gene/10090:Kcnn4 ^@ http://purl.uniprot.org/uniprot/O89109 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel KCNN family. KCa3.1/KCNN4 subfamily.|||Cell membrane|||Forms a voltage-independent potassium channel that is activated by intracellular calcium (PubMed:9705284). Activation is followed by membrane hyperpolarization which promotes calcium influx. Required for maximal calcium influx and proliferation during the reactivation of naive T-cells (PubMed:20884616). Plays a role in the late stages of EGF-induced macropinocytosis (By similarity).|||Heterotetramer of potassium channel proteins (Probable). Interacts with MTMR6 (By similarity).|||Phosphorylation at His-356 by NDKB activates the channel, and conversely it's dephosphorylation by PHPT1 inhibits the channel.|||The channel is inhibited by clotrimazole and charybdotoxin but is insensitive to apamin. http://togogenome.org/gene/10090:Coq7 ^@ http://purl.uniprot.org/uniprot/P97478|||http://purl.uniprot.org/uniprot/Q3TYT1 ^@ Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the COQ7 family.|||Binds 2 iron ions per subunit.|||Catalyzes the hydroxylation of 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2) during ubiquinone biosynthesis. Has also a structural role in the COQ enzyme complex, stabilizing other COQ polypeptides (By similarity). Involved in lifespan determination in a ubiquinone-independent manner (PubMed:19478076). Plays a role in modulating mitochondrial stress responses, acting in the nucleus, perhaps via regulating gene expression, independent of its characterized mitochondrial function in ubiquinone biosynthesis.|||Catalyzes the hydroxylation of 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2) during ubiquinone biosynthesis. Has also a structural role in the COQ enzyme complex, stabilizing other COQ polypeptides. Involved in lifespan determination in a ubiquinone-independent manner.|||Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with ADCK4 and COQ6. Interacts with COQ9.|||Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with COQ8B and COQ6. Interacts with COQ9.|||Highly expressed in tissues with high energy demand such as heart, muscle, liver, and kidney.|||In life-span analysis, transgenic expression reverted the extended life span of clk-1 to the comparable level with wild-type control.|||Mice lacking Coq7 start to die after E8. Heterozygous mutant reveal that the reduction of Coq7 levels in these animals profoundly alters their mitochondrial function despite the fact that ubiquinone production is unaffected. The mitochondria of young mutants heterozygous are dysfunctional, exhibiting reduced energy metabolism and a substantial increase in oxidative stress.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Agk ^@ http://purl.uniprot.org/uniprot/Q9ESW4 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AGK family.|||Both the ceramide and diacylglycerol kinase activities are inhibited by sphingosine and stimulated by cardiolipin (PubMed:15252046). Both activities are stimulated by calcium when magnesium concentrations are low but inhibited by calcium when magnesium concentrations are high (PubMed:15252046).|||Component of the TIM22 complex, which core is composed of TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and TIMM29.|||Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively (PubMed:15252046). Phosphorylates ceramide but not sphingosine (PubMed:15252046). Phosphorylates 1,2-dioleoylglycerol more rapidly than 2,3-dioleoylglycerol (PubMed:18004883). Independently of its lipid kinase activity, acts as a component of the TIM22 complex (By similarity). The TIM22 complex mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane by forming a twin-pore translocase that uses the membrane potential as the external driving force (By similarity). In the TIM22 complex, required for the import of a subset of metabolite carriers into mitochondria, such as ANT1/SLC25A4 and SLC25A24, while it is not required for the import of TIMM23 (By similarity). Overexpression increases the formation and secretion of LPA, resulting in transactivation of EGFR and activation of the downstream MAPK signaling pathway, leading to increased cell growth (By similarity).|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||Ubiquitously expressed.|||Was originally (PubMed:15252046) thought to have ceramide kinase activity. Such activity is however unlikely in vivo. http://togogenome.org/gene/10090:Nog ^@ http://purl.uniprot.org/uniprot/A2RTJ4|||http://purl.uniprot.org/uniprot/P97466 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the noggin family.|||Defects in Nog are the cause of a recessive lethal phenotype at birth. Multiple defects include a failure of neural tube closure, broad club-shaped limbs, loss of caudal vertebrae, a shortened body axis, and retention of a small vestigial tail.|||Embryonic expression was first detected in the node at 7.5 dpc. By early somite stages, expression extends anteriorly along the entire length of the notochord and is expressed in the dorsal neural tube from the caudal hindbrain to the posterior-most region of the embryo. By the time cranial tube closure is completed expression is continuous along most of the dorsal midline of the neural tube, to its rostral termination at the base of the forebrain. Expression in the neural tube and caudal notochord remains unchanged during early organogenesis from 9.5 dpc to 10.5 dpc.|||Essential for cartilage morphogenesis and joint formation. Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite (PubMed:9585504, PubMed:9603738). Inhibits chondrocyte differentiation through its interaction with GDF5 and, probably, GDF6 (By similarity).|||Expressed in condensing cartilage and immature chondrocytes.|||Homodimer.|||Homodimer. Interacts with GDF5; inhibits chondrocyte differentiation.|||Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite.|||Secreted http://togogenome.org/gene/10090:Nckap1l ^@ http://purl.uniprot.org/uniprot/Q8K1X4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Essential hematopoietic-specific regulator of the actin cytoskeleton. Controls lymphocyte development, activation, proliferation and homeostasis, erythrocyte membrane stability, as well as phagocytosis and migration by neutrophils and macrophages (PubMed:19015308, PubMed:23424621). Component of the WAVE2 complex which signals downstream of RAC to stimulate F-actin polymerization (PubMed:23424621). Required for stabilization and/or translation of the WAVE2 complex proteins in hematopoietic cells (PubMed:19015308). Within the WAVE2 complex, enables the cortical actin network to restrain excessive degranulation and granule release by T-cells. Required for efficient T-lymphocyte and neutrophil migration (By similarity). Exhibits complex cycles of activation and inhibition to generate waves of propagating the assembly with actin. Also involved in mechanisms WAVE independent to regulate myosin and actin polymerization during neutrophil chemotaxis (By similarity). In T-cells, required for proper mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, cell proliferation and cytokine secretion, including that of IL2 and TNF (By similarity).|||In hematopoietic cells, component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1L/HEM1 and WASF2/WAVE2. Interacts with ARHGAP4, PIK3C3/VPS34 and PPP1R12A/MYPT1. Interacts with mammalian target of rapamycin complex 2 (mTORC2) components, including MTOR and RICTOR.|||Membrane|||Mutants exhibit lymphopenia, neutrophilia and anemia. T cell development is disrupted at the CD4(-)CD8(-) to CD4(+)CD8(+) cell stages and T cell activation and adhesion are impaired. Neutrophils fail to migrate in response to chemotactic agents and are deficient in their ability to phagocytose bacteria. They show enhanced Th17 cells production (PubMed:19015308). The anemia is microcytic, hypochromic and characterized by abnormally shaped erythrocytes with aberrant F-actin foci and decreased lifespan (PubMed:23424621).|||Predominantly expressed in developing and mature hematopoietic cells. Also detected in urogenital tissues, including testis. http://togogenome.org/gene/10090:Tafa3 ^@ http://purl.uniprot.org/uniprot/Q7TPG6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TAFA family.|||By ischemia. Up-regulated in the microglia in the middle cerebral artery occlusion (MCAO), expression reduced back to control level at 14 days after MCAO.|||Highly expressed in brain, in regions such as the hippocampus, the habenular, thalamic nuclei and hypophysial pars tuberalis (PubMed:25595455). Expression levels in the hypophysial pars tuberalis vary between day and night: they are low at mid-day and high at mid-night. The expression in the other regions do not display a day/night difference (PubMed:22426341).|||Plays a role in the regulation of microglia polarization.|||Secreted http://togogenome.org/gene/10090:Tmem237 ^@ http://purl.uniprot.org/uniprot/Q3V0J1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM237 family.|||Component of the transition zone in primary cilia. Required for ciliogenesis.|||Membrane|||Part of the tectonic-like complex (also named B9 complex). Interacts with TMEM107.|||cilium http://togogenome.org/gene/10090:Lurap1 ^@ http://purl.uniprot.org/uniprot/Q9D6I9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as an activator of the canonical NF-kappa-B pathway and drive the production of pro-inflammatory cytokines. Promotes the antigen (Ag)-presenting and priming function of dendritic cells via the canonical NF-kappa-B pathway. In concert with MYO18A and CDC42BPA/CDC42BPB, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Activates CDC42BPA/CDC42BPB and targets it to actomyosin through its interaction with MYO18A, leading to MYL9/MLC2 phosphorylation and MYH9/MYH10-dependent actomyosin assembly in the lamella (By similarity).|||Cytoplasm|||Forms a tripartite complex with CDC42BPA/CDC42BPB and MYO18A acting as an adapter connecting both. Its binding to CDC42BPA/CDC42BPB results in their activation by abolition of their negative autoregulation. Interacts with CDC42BPA and CDC42BPB.|||Phosphorylated. http://togogenome.org/gene/10090:Elmod2 ^@ http://purl.uniprot.org/uniprot/Q8BGF6 ^@ Function ^@ Acts as a GTPase-activating protein (GAP) toward guanine nucleotide exchange factors like ARL2, ARL3, ARF1 and ARF6, but not for GTPases outside the Arf family. http://togogenome.org/gene/10090:Marchf2 ^@ http://purl.uniprot.org/uniprot/Q99M02 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||E3 ubiquitin-protein ligase that may mediate ubiquitination of TFRC and CD86, and promote their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. Together with GOPC/CAL mediates the ubiquitination and lysosomal degradation of CFTR (By similarity). Ubiquitinates and therefore mediates the degradation of DLG1 (By similarity). Regulates the intracellular trafficking and secretion of alpha1-antitrypsin/SERPINA1 and HP/haptoglobin via ubiquitination and degradation of the cargo receptor ERGIC3 (By similarity). Negatively regulates the antiviral and antibacterial immune response by repression of the NF-kB and type 1 IFN signaling pathways, via MARCHF2-mediated K48-linked polyubiquitination of IKBKG/NEMO, resulting in its proteasomal degradation (PubMed:32935379). May be involved in endosomal trafficking through interaction with STX6.|||Endoplasmic reticulum membrane|||Endosome membrane|||Golgi apparatus membrane|||Induced in macrophages by viral or bacterial infection.|||Interacts with STX6; the interaction promotes MARCHF2-mediated ubiquitination and degradation of CFTR (By similarity). Interacts with MARCHF3 (By similarity). Interacts with GOPC/CAL; the interaction leads to CFTR ubiquitination and degradation (By similarity). Interacts with CFTR; the interaction leads to CFTR ubiqtuitination and degradation (By similarity). Interacts (via PDZ domain) with DLG1 (via PDZ domains); the interaction leads to DLG1 ubiqtuitination and degradation (By similarity). Interacts with ERGIC3 (By similarity). Interacts with ADRB2 (By similarity). Interacts with IKBKG/NEMO; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO (PubMed:32935379).|||Knockout mice are phenotypically normal (PubMed:32935379). Increase in cytokine production following viral and bacterial challenge, including increases in Ifnb1, Il6, Il12, Ccl5, Cxcl10 and Tnf protein abundance (PubMed:32935379). Increase in survival following exposure to a lethal dose of L.monocytogenes and decrease in bacterial load in the spleen and liver (PubMed:32935379). Increase in susceptibility to endotoxin shock (PubMed:32935379).|||Lysosome membrane|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Odf3 ^@ http://purl.uniprot.org/uniprot/Q920N1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 'Shippo' is a Japanese word for tail.|||Belongs to the CIMAP family.|||Cytoplasm|||Outer dense fibers are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail. May help to maintain the passive elastic structures and elastic recoil of the sperm tail.|||Testis-specific (at protein level). Expression restricted to the germ cell fraction, absent in somatic cell fractions such as Sertoli and Leydig cells. Expression detected in the third week postpartum (23 days) after haploid germ cells developed, expression increased with age. Expressed in the tails of elongated spermatids sticking out toward the tubular lumen, and in cytoplasmic droplets still attached to the spermatid tail membrane. Expressed in the tails of mature sperm, from the connecting piece proximal to the head, along the middle and principal pieces, down to the distal end piece.|||flagellum http://togogenome.org/gene/10090:Orc3 ^@ http://purl.uniprot.org/uniprot/Q9JK30 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORC3 family.|||Chromosome|||Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase.|||Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3.|||It is uncertain whether Met-1 or Met-8 is the initiator.|||Multi-mono-ubiquitinated by OBI1; ubiquitination is important for efficient DNA replication origin site activation. Ubiquitination levels are low in mitotic and early G1-phAse cells and are induced in late G1-/early S-phase, peaking in S-phase and decrease toward the end of the cell cycle.|||Nucleus http://togogenome.org/gene/10090:Tspyl4 ^@ http://purl.uniprot.org/uniprot/Q8VD63 ^@ Similarity ^@ Belongs to the nucleosome assembly protein (NAP) family. http://togogenome.org/gene/10090:Or9g20 ^@ http://purl.uniprot.org/uniprot/A2ASV2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Acat1 ^@ http://purl.uniprot.org/uniprot/Q8QZT1 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by potassium ions, but not sodium ions.|||Belongs to the thiolase-like superfamily. Thiolase family.|||Homotetramer.|||Mitochondrion|||Succinylation at Lys-265, adjacent to a coenzyme A binding site. Desuccinylated by SIRT5.|||This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA. Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms. The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA. Thereby, it plays a major role in ketone body metabolism. http://togogenome.org/gene/10090:Dnaaf6b ^@ http://purl.uniprot.org/uniprot/Q8C6P5 ^@ Similarity ^@ Belongs to the PIH1 family. http://togogenome.org/gene/10090:Xxylt1 ^@ http://purl.uniprot.org/uniprot/Q3U4G3 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha-1,3-xylosyltransferase, which elongates the O-linked xylose-glucose disaccharide attached to EGF-like repeats in the extracellular domain of target proteins by catalyzing the addition of the second xylose. Known targets include Notch proteins and coagulation factors, such as F9.|||Belongs to the glycosyltransferase 8 family.|||Endoplasmic reticulum membrane|||Has the highest in vitro activity with 20 mM Mn(2+), a concentration entirely out of the physiological range. Can also utilize Mg(2+), suggesting this may be the physiological cofactor.|||Homodimer (PubMed:26414444). Dimer formation may be essential for the retention in endoplasmic reticulum (Probable).|||It is uncertain whether Met-1 or Met-14 is the initiator. http://togogenome.org/gene/10090:Zfp182 ^@ http://purl.uniprot.org/uniprot/Q6P560 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Pla2g4d ^@ http://purl.uniprot.org/uniprot/Q50L43 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position (PubMed:15866882). Compared to its human ortholog, may have no preference for the fatty acid found at the sn-2 position (PubMed:15866882).|||Membrane|||Stimulated by cytosolic Ca(2+).|||The N-terminal C2 domain mediates the association with lipid membranes upon calcium binding. An additional second C2 domain may stand in between the C2 domain and the PLA2c domain.|||Weakly or not expressed in most tissues. Detected in placenta of 17.5 dpc embryos.|||cytosol http://togogenome.org/gene/10090:Map4k4 ^@ http://purl.uniprot.org/uniprot/P97820 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Appears to be ubiquitous, expressed in all tissue types examined. Highest levels observed in heart and brain.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Interacts with the SH3 domain of the adapter proteins Nck. Interacts (via its CNH regulatory domain) with ATL1 (via the N-terminal region). Interacts with RAP2A (GTP-bound form preferentially) (By similarity).|||Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322 (By similarity). http://togogenome.org/gene/10090:Polr2c ^@ http://purl.uniprot.org/uniprot/P97760 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.|||Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB11/POLR2J and RPB3/POLR2C subunits interact with each other.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fam228a ^@ http://purl.uniprot.org/uniprot/Q8CDW1 ^@ Similarity ^@ Belongs to the FAM228 family. http://togogenome.org/gene/10090:Kazn ^@ http://purl.uniprot.org/uniprot/Q69ZS8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the kazrin family.|||Cell junction|||Component of the cornified envelope of keratinocytes. May be involved in the interplay between adherens junctions and desmosomes. The function in the nucleus is not known.|||Expressed in eggs and early embryos. Detected in unfertilized eggs associated with the spindle apparatus and cytoskeletal sheets. As quickly as 5 min after egg activation, relocates to a diffuse peri-spindle position, followed 20-30 min later by localization to the presumptive cytokinetic ring. Before the blastocyst stage of development, associates with the nuclear matrix in a cell cycle-dependent manner, and also associates with the cytoplasmic actin cytoskeleton. After blastocyst formation, is found associating with cell-cell junctions, the cytoskeleton and nucleus.|||Expressed in skin interfollicular epidermis and hair follicles. Expressed in tongue epithelium basal suprabasal layers.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Pclo ^@ http://purl.uniprot.org/uniprot/Q9QYX7 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 3 Ca(2+) ions per C2 domain.|||C2 domain 1 is involved in binding calcium and phospholipids. Calcium binds with low affinity but with high specificity and induces a large conformational change.|||Highly expressed in brain. Moderately expressed in pituitary gland and pancreatic islets. Low levels found in stomach.|||Interacts with BSN, ERC2/CAST1, RIMS1 and UNC13A (PubMed:10508862, PubMed:12401793). Interacts (via C-terminus) with TRIO (via N-terminus) (By similarity). Interacts with CTBP1 (By similarity). Interacts with SIAH1; this interaction negatively regulates SIAH1 E3 ligase activity (By similarity). Directly interacts with GIT1 and GIT2 (By similarity).|||Knockdown of both Bassoon/BSN and Piccolo/PCLO leads to the formation of presynaptic autophagosomes.|||Presynaptic active zone|||Probable cloning artifact.|||Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released (PubMed:19812333). After synthesis, participates in the formation of Golgi-derived membranous organelles termed Piccolo-Bassoon transport vesicles (PTVs) that are transported along axons to sites of nascent synaptic contacts (By similarity). At the presynaptic active zone, regulates the spatial organization of synaptic vesicle cluster, the protein complexes that execute membrane fusion and compensatory endocytosis (By similarity). Organizes as well the readily releasable pool of synaptic vesicles and safeguards a fraction of them to be not immediately available for action potential-induced release (By similarity). Functions also in processes other than assembly such as the regulation of specific presynaptic protein ubiquitination by interacting with SIAH1 or the regulation of presynaptic autophagy (PubMed:28231469) (By similarity). Mediates also synapse to nucleus communication leading to reconfiguration of gene expression by associating with the transcriptional corepressor CTBP1 and by subsequently reducing the size of its pool available for nuclear import (By similarity).|||Unlikely isoform. Several sequence problems. http://togogenome.org/gene/10090:Rdh11 ^@ http://purl.uniprot.org/uniprot/Q9QYF1 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Deficient mice are fertile and developed normally but exhibit delayed dark adaptation vision (PubMed:15790565). Testis and livers of deficient mice exhibit a lower rate of all-trans-retinal conversion to all-trans-retinol (PubMed:29567832).|||Down-regulated in liver by fasting and rose by refeeding.|||Endoplasmic reticulum membrane|||Expressed at high level in liver and testis (PubMed:12807874, PubMed:15790565, PubMed:29567832). Expressed at lower levels in smooth muscle, thymus, submaxillary gland and epididymis. In testis, expression is restricted to pachytene spermatocytes. Also expressed in four layers of the retina, including the outer segment of rods and cones (PubMed:12807874, PubMed:15790565).|||Not glycosylated.|||Retinol dehydrogenase with a clear preference for NADP (PubMed:12807874, PubMed:29567832). Displays high activity towards 9-cis, 11-cis and all-trans-retinol, and to a lesser extent on 13-cis-retinol (By similarity) (PubMed:12807874). Exhibits also reductive activity towards toxic lipid peroxidation products such as medium-chain aldehydes trans-2-nonenal, nonanal, and cis-6-nonenal (PubMed:12807874). Has no dehydrogenase activity towards steroid (PubMed:12807874). Seems to be required for homeostasis of retinol in liver and testis (PubMed:29567832).|||Shows clear specificity for the pro-S hydrogen on C4 of NADPH and the pro-R hydrogen on C15 of retinols. http://togogenome.org/gene/10090:Lamp2 ^@ http://purl.uniprot.org/uniprot/P17047|||http://purl.uniprot.org/uniprot/Q8C5K0 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ About half of the mutant mice die between 20 and 40 days after birth. Survivors are smaller, weigh 10 to 15 % less than their littermates, but show normal lifespan. Both mice that die early and long-time survivors display an accumulation of autophagic vacuoles in liver, pancreas, cardiac and skeletal muscle. Mutant mice display an increased ratio of heart weight to body weight and severely impaired contractile function of the heart muscle. Hepatocytes from mutant mice show a decreased rate of degradation of long-lived proteins.|||Belongs to the LAMP family.|||Cell membrane|||Detected in liver and kidney (at protein level). Detected in liver and kidney.|||Endosome membrane|||Extensively N-glycosylated. Contains a minor proportion of O-linked glycans.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:10972293). Acts as an important regulator of lysosomal lumen pH regulation by acting as a direct inhibitor of the proton channel TMEM175, facilitating lysosomal acidification for optimal hydrolase activity (By similarity). Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live (By similarity). Functions by binding target proteins, such as GAPDH, NLRP3 and MLLT11, and targeting them for lysosomal degradation (By similarity). In the chaperone-mediated autophagy, acts downstream of chaperones, such as HSPA8/HSC70, which recognize and bind substrate proteins and mediate their recruitment to lysosomes, where target proteins bind LAMP2 (By similarity). Plays a role in lysosomal protein degradation in response to starvation (PubMed:27628032). Required for the fusion of autophagosomes with lysosomes during autophagy (PubMed:27628032). Cells that lack LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on autophagosomes, which is the most likely explanation for the lack of fusion between autophagosomes and lysosomes (PubMed:27628032). Required for normal degradation of the contents of autophagosomes (PubMed:10972293, PubMed:12221139). Required for efficient MHCII-mediated presentation of exogenous antigens via its function in lysosomal protein degradation; antigenic peptides generated by proteases in the endosomal/lysosomal compartment are captured by nascent MHCII subunits (By similarity). Is not required for efficient MHCII-mediated presentation of endogenous antigens (By similarity).|||Lysosome membrane|||Membrane|||Monomer. Forms large homooligomers (By similarity). Interacts (via its cytoplasmic region) with HSPA8; HSPA8 mediates recruitment of proteins with a KFERQ motif to the surface of the lysosome for chaperone-mediated autophagy (By similarity). Interacts with HSP90 in the lysosome lumen; this enhances LAMP2 stability (By similarity). Interacts with MLLT11 (By similarity). Interacts with ABCB9 (PubMed:22641697). Interacts with FURIN (By similarity). Interacts with CT55; this interaction may be important for LAMP2 protein stability (By similarity). Interacts with TMEM175; inhibiting the proton channel activity of TMEM175 (By similarity).|||autophagosome membrane http://togogenome.org/gene/10090:Uchl3 ^@ http://purl.uniprot.org/uniprot/Q8BWQ9|||http://purl.uniprot.org/uniprot/Q9JKB1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C12 family.|||Cytoplasm|||Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3'', and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome.|||Expressed at 8.5 dpc in structures required for skeletal patterning. Highly expressed at 11 dpc, and decreases markedly from 15 dpc.|||Inhibited by monoubiquitin and diubiquitin.|||Mice have no developmental defects, are fertile, and show normal T-cell differentiation. They have normal anxiety, locomotor behavior, motor function and synaptic transmission, but show defects in spatial learning and working memory. Exhibit stress-related effects with profound apoptosis-mediated germ cell loss and also, prominent retinal degeneration with photoreceptor cell apoptosis and mitochondrial oxidative stress. Mice show reduced capacity for adipocyte differentiation and impaired insulin responses.|||Preferentially binds diubiquitin; the interaction does not hydrolyze diubiquitin but, in vitro, inhibits the hydrolyzing activity on other substrates.|||Ubiquitously expressed, with highest levels in brain, liver, heart, thymus, kidney and testis. Highly expressed in the cauda epididymidis, in meiotic pachytene spermatocytes and post-meiotic spematids. In the retina, enriched in the photoreceptor inner segment. http://togogenome.org/gene/10090:Trim33 ^@ http://purl.uniprot.org/uniprot/Q99PP7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway (By similarity). May act as a transcriptional repressor (By similarity). Inhibits the transcriptional response to TGF-beta/BMP signaling cascade (By similarity). Plays a role in the control of cell proliferation (By similarity). Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor. Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade) (By similarity).|||Belongs to the TRIM/RBCC family.|||Expressed in round hematopoietic cells in yolk sac blood islands at 8.5 dpc. Expressed uniformly at 10.5 dpc. Expressed in the brain, spinal cord, neuroepithelium and in spinal ganglia at 12.5 dpc. Expressed in brain, spinal cord, developing epithelia of the lung, stomach, intestine, outer region of the developing kidney, liver, brown fat tissue, skeletal muscle, developing craniofacial region, thymus, cochlear and pharyngeal epithelia and olfactory and respiratory epithelia at 16.5 dpc.|||Homooligomer and heterooligomer with TRIM24 and TRIM28 family members (By similarity). Interacts with SMAD4 in unstimulated cells (By similarity). Found in a complex with SMAD2 and SMAD3 upon addition of TGF-beta (By similarity). Interacts with SMAD2 and SMAD3 (By similarity). Interacts with SMAD4 under basal and induced conditions and, upon TGF-beta signaling, with activated SMAD2. Forms a ternary complex with SMAD4 and SMAD2 upon TGF-beta signaling (By similarity).|||Nucleus|||Sumoylated with SUMO1.|||Ubiquitous with high level in testis. http://togogenome.org/gene/10090:Sfi1 ^@ http://purl.uniprot.org/uniprot/Q3UZY0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SFI1 family.|||CETN2-binding regions contains a conserved Trp residue in their C-terminal ends, which seems critical for interaction with CETN2.|||Interacts with CETN2 (via C-terminus).|||Plays a role in the dynamic structure of centrosome-associated contractile fibers via its interaction with CETN2.|||centriole http://togogenome.org/gene/10090:Cap1 ^@ http://purl.uniprot.org/uniprot/P40124 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAP family.|||Cell membrane|||Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity.|||Homodimer. Binds actin monomers (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Gphb5 ^@ http://purl.uniprot.org/uniprot/B2RTN6|||http://purl.uniprot.org/uniprot/Q812B2 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycoprotein hormones subunit beta family.|||Expressed in the anterior lobe of pituitary.|||Functions as a heterodimeric glycoprotein hormone with GPHA2 able to bind and activate the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production. Plays a central role in controlling thyroid cell metabolism.|||Heterodimer with GPHA2; this heterodimer interacts with thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP production.|||N-glycosylated.|||Overexpression of Gphb5 results in proptosis, elevated serum T4 levels and significantly reduced body weight.|||Secreted http://togogenome.org/gene/10090:Or6c1b ^@ http://purl.uniprot.org/uniprot/Q8VFH8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gstz1 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VNC1|||http://purl.uniprot.org/uniprot/Q9WVL0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Zeta family.|||Cytoplasm|||Expressed in liver, kidney, seminal glands and breast.|||Glutathione is required for the MAAI activity.|||Homodimer.|||Probable bifunctional enzyme showing minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1, 3-diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with t-butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid (By similarity). http://togogenome.org/gene/10090:Gm10058 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Wdcp ^@ http://purl.uniprot.org/uniprot/Q6NV72 ^@ PTM|||Subunit ^@ Oligomer. Interacts with HCK (via SH3 domain).|||Phosphorylated on Tyr when associated with HCK. http://togogenome.org/gene/10090:Nkapl ^@ http://purl.uniprot.org/uniprot/Q5SZT7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKAP family.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with RBPJ, CIR1 and HDAC3.|||Nucleus|||Specific to testis (at protein level). Detected in differenting spermatogonia and early spermatocytes (at protein level).|||Strongly expressed in testis from 3 weeks onwards.|||Transcriptional repressor of Notch-mediated signaling. Required for spermatogenesis.|||Viable. Males are infertile with reduced testis size, while female fertility is not affected. In the testis, germ cell development arrests at the pachytene spermatocyte stage leading to complete absence of mature spermatozoa. http://togogenome.org/gene/10090:Commd6 ^@ http://purl.uniprot.org/uniprot/Q3V4B5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Interacts (via COMM domain) with COMMD1 (via COMM domain). Does not interact with NFKBIB. Interacts with RELA, RELB, NFKB1/p105. Does not interact with NFKBIB. Interacts with CCDC22, CCDC93, SCNN1B, CUL4A.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Inhibits TNF-induced NFKB1 activation.|||Nucleus http://togogenome.org/gene/10090:A430033K04Rik ^@ http://purl.uniprot.org/uniprot/E9Q8G5 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed during osteogenic differentiation where levels increase from the first days of differentiation and remain high during the whole process (PubMed:30654721). Highly expressed in lung (PubMed:30654721).|||May modulate osteogenic differentiation, at least in part, through the bone morphogenetic protein (BMP) signaling pathway, increasing RUNX2 activation and leading to osteoblast commitment and maturation.|||Nucleus|||Polyubiquitinated, leading to its degradation via the ubiquitin-proteasome pathway.|||Up-regulated during osteogenic differentiation. http://togogenome.org/gene/10090:Mapk15 ^@ http://purl.uniprot.org/uniprot/Q80Y86 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by threonine and tyrosine phosphorylation (By similarity). Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Phosphorylation and activation in response to DNA damaging agents, serum stimulation. Constitutively activated when phosphorylated on Tyr-178. Activity depends on the relative rates of MAPK15 autophosphorylation and dephosphorylation by PTPN1 (By similarity).|||Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (By similarity) (PubMed:25823377). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation. Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling. Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins. Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion. Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA. Regulates DA transporter (DAT) activity and protein expression via activation of RhoA. In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (By similarity). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (By similarity). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (PubMed:23351492). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (By similarity).|||Autophosphorylated on Thr-176 and Tyr-178; activates the enzyme.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Cytoplasm|||Expressed at all stages of oocyte meiotic maturation.|||Golgi apparatus|||Interacts with TGFB1I1 (PubMed:16624805). Interacts with CSK/c-Src, ABL1 and RET. Interacts with GABARAP, MAP1LC3B and GABARAPL1; controls, in a kinase-dependent fashion, both basal and starvation-induced autophagy. Interacts with ESRRA; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity. Interacts with PCNA; the interaction is chromatin binding- and kinase activity-dependent and prevents MDM2-mediated PCNA destruction by inhibiting the association of PCNA with MDM2 (By similarity). Interacts with DVL2 (PubMed:25823377). Interacts with CLIC3; MAPK15 does not phosphorylates CLIC3 (By similarity).|||Nucleus|||The N-terminal region (1-20) is the minimal region necessary for ubiquitination and further proteasomal degradation.|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.|||Ubiquitinated. Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase (By similarity).|||autophagosome|||centriole|||cilium basal body|||spindle|||tight junction http://togogenome.org/gene/10090:Lrrc8d ^@ http://purl.uniprot.org/uniprot/Q8BGR2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRC8 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in pancreatic beta cells (PubMed:29773801). Also expressed in glucagon-secreting pancreatic alpha cells (PubMed:29773801).|||Heterohexamer (Probable). Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8C and/or LRRC8E) to form a heterohexamer. In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (PubMed:24782309).|||Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:29773801). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Plays a redundant role in the efflux of amino acids, such as aspartate, in response to osmotic stress family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (By similarity). Also acts as a regulator of glucose-sensing in pancreatic beta cells: VRAC currents, generated in response to hypotonicity- or glucose-induced beta cell swelling, depolarize cells, thereby causing electrical excitation, leading to increase glucose sensitivity and insulin secretion (PubMed:29773801). VRAC channels containing LRRC8D inhibit transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (By similarity).|||The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins. http://togogenome.org/gene/10090:Atp6v1g1 ^@ http://purl.uniprot.org/uniprot/Q5HZY7|||http://purl.uniprot.org/uniprot/Q9CR51 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the V-ATPase G subunit family.|||Kidney; localizes to early distal nephron, encompassing thick ascending limbs and distal convoluted tubules (at protein level)(PubMed:29993276). Ubiquitous (PubMed:12527205).|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (By similarity).|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. http://togogenome.org/gene/10090:Txnl4b ^@ http://purl.uniprot.org/uniprot/Q8BUH1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DIM1 family.|||Essential role in pre-mRNA splicing. Required in cell cycle progression for S/G(2) transition (By similarity).|||Homodimer. Interacts with the U5-102 kDa protein subunit of the spliceosome (By similarity).|||Nucleus http://togogenome.org/gene/10090:Anapc16 ^@ http://purl.uniprot.org/uniprot/Q9CPV2|||http://purl.uniprot.org/uniprot/S4R2B6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APC16 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.|||Cytoplasm|||Nucleus|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. ANAPC16 associates with the rest of the complex independently of ANAPC2 and ANAPC11.|||kinetochore http://togogenome.org/gene/10090:Enox1 ^@ http://purl.uniprot.org/uniprot/Q8BHR2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ENOX family.|||Cell membrane|||Not inhibited by the antitumor sulfonylurea LY181984, the vabilloid capsaicin, and retinoids.|||Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 24 minutes and play a role in control of the ultradian cellular biological clock (By similarity).|||extracellular space http://togogenome.org/gene/10090:Cryba2 ^@ http://purl.uniprot.org/uniprot/Q9JJV1 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms (By similarity). http://togogenome.org/gene/10090:Tnf ^@ http://purl.uniprot.org/uniprot/A0A0R4J210|||http://purl.uniprot.org/uniprot/P06804|||http://purl.uniprot.org/uniprot/Q3U593 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (PubMed:25586176). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (By similarity). Promotes osteoclastogenesis and therefore mediates bone resorption (PubMed:32741026).|||Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6.|||Homotrimer. Interacts with SPPL2B.|||Interacts with SPPL2B (By similarity). Homotrimer.|||Membrane|||O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.|||Secreted|||The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.|||The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1 (By similarity).|||The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.|||The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space (By similarity). The soluble form derives from the membrane form by proteolytic processing.|||The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.|||The soluble form is demyristoylated by SIRT6, promoting its secretion. http://togogenome.org/gene/10090:Krt25 ^@ http://purl.uniprot.org/uniprot/Q8VCW2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Essential for the proper assembly of type I and type II keratin protein complexes and formation of keratin intermediate filaments in the inner root sheath (irs) (PubMed:14996088, PubMed:17920809). Plays a role in the cytoskeleton organization (By similarity).|||Heterodimer of a type I and a type II keratin (PubMed:14996088). Heterodimer with type II keratin KRT5 leading to the formation of keratin intermediate filament (KIF) network. Interacts with KRT6A to form filaments (By similarity).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Krr1 ^@ http://purl.uniprot.org/uniprot/Q8BGA5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KRR1 family.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Trabd2b ^@ http://purl.uniprot.org/uniprot/B1ATG9 ^@ Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TIKI family.|||Cell membrane|||Divalent metal cations. Mn(2+) or Co(2+).|||Highly expressed in heart and kidney. Also found in white and brown adipose tissue.|||Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the 8 N-terminal residues of a subset of Wnt proteins. Following cleavage, Wnt proteins become oxidized and form large disulfide-bond oligomers, leading to their inactivation. Able to cleave WNT3A, WNT5, but not WNT11. Required for head formation (By similarity).|||Transiently induced during 3T3-L1 cell differentiation into adipocytes. In vivo, down-regulated by fasting in both white and brown adipose tissues. High-fat diet down-regulates expression in white adipose tissue and up-regulates it in brown adipose tissue. http://togogenome.org/gene/10090:Plk5 ^@ http://purl.uniprot.org/uniprot/G3X967|||http://purl.uniprot.org/uniprot/Q4FZD7 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.|||Cytoplasm|||Down-regulated in proliferating cells or in serum-stimulated cells or growth factors. Up-regulated in asynchronous cells, or upon serum deprivation or following stress inducible DNA damage treatment.|||Expressed in the cerebellum, eye and brain cortex (at protein level). Expressed in highly differentiated tissues, such as brain, eyes and ovary. Not detectable in proliferating tissues, such as the colon, spleen and placenta.|||Inactive serine/threonine-protein kinase that plays a role in cell cycle progression and neuronal differentiation.|||The protein kinase domain is predicted to be catalytically inactive; has lost the main activatory autophosphorylation site and the conserved key residues involved in phospho-substrate. The C-terminal region (containing the POLO box domain) is sufficient for inducing cell cycle arrest (By similarity).|||nucleolus http://togogenome.org/gene/10090:Prn ^@ http://purl.uniprot.org/uniprot/A0A075B668 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the prion family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem121b ^@ http://purl.uniprot.org/uniprot/B2RQD1|||http://purl.uniprot.org/uniprot/Q99MX7 ^@ Similarity ^@ Belongs to the TMEM121 family. http://togogenome.org/gene/10090:Ldhc ^@ http://purl.uniprot.org/uniprot/P00342|||http://purl.uniprot.org/uniprot/Q548Z6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LDH/MDH superfamily. LDH family.|||Cytoplasm|||Expressed within the midpiece of sperm tail (at protein level).|||Homotetramer. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2.|||Possible role in sperm motility. http://togogenome.org/gene/10090:Aatk ^@ http://purl.uniprot.org/uniprot/Q80YE4 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylated by CDK5 (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Cytoplasm|||Expressed in brain, and, to a lower extent, in kidney, heart, lung and skeletal muscle. In the brain, expressed in the olfactory bulb, cerebellum, striatum, hippocampal formation, thalamus, hypothalamus, and pontine nuclei (at protein level).|||Interacts with CDK5.|||Isoform 2 is predominantly expressed in adult stage. Isoform 3 is up-regulated during postnatal development.|||May be involved in neuronal differentiation.|||Membrane|||Up-regulated during the apoptotic death of myeloid cells induced by cytokine withdrawal, such as IL3, and during G-CSF-induced terminal differentiation of myeloblasts to granulocytes.|||axon|||dendrite|||growth cone|||perinuclear region http://togogenome.org/gene/10090:Megf6 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQ83 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Proser3 ^@ http://purl.uniprot.org/uniprot/Q7TSA6 ^@ Subcellular Location Annotation ^@ centrosome http://togogenome.org/gene/10090:Mlf2 ^@ http://purl.uniprot.org/uniprot/Q3UNV7|||http://purl.uniprot.org/uniprot/Q99KX1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MLF family.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Clec1b ^@ http://purl.uniprot.org/uniprot/Q9JL99 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a receptor for the platelet-aggregating snake venom protein rhodocytin. Rhodocytin binding leads to tyrosine phosphorylation and this promotes the binding of spleen tyrosine kinase (Syk) and initiation of downstream tyrosine phosphorylation events and activation of PLC-gamma-2 (PubMed:16174766).|||C-type lectin-like receptor that functions as a platelet receptor for the lymphatic endothelial marker, PDPN. After ligand activation, signals via sequential activation of SRC and SYK tyrosine kinases leading to activation of PLCG2.|||Glycosylated.|||Hematopoietic cells, megakaryocytes and platelets.|||Homodimer. Interacts (via cytoplasmic domain) with RACK1; promotes CLEC1B ubiquitination and proteasome-mediated degradation. Interacts (dimer) with SYK (via SH2 domains) (By similarity). Interacts with PDPN; the interaction is independent of CLEC1B glycosylation and activates CLEC1B (By similarity).|||Membrane|||Phosphorylated on tyrosine residue in response to rhodocytin binding. http://togogenome.org/gene/10090:Dmc1 ^@ http://purl.uniprot.org/uniprot/Q14AN8|||http://purl.uniprot.org/uniprot/Q61880|||http://purl.uniprot.org/uniprot/Q8C610 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RecA family. DMC1 subfamily.|||Chromosome|||Double stacked ring-shaped homooctamer (By similarity). Interacts with BRCA2 (By similarity). Interacts with the MND1-PSMC3IP heterodimer (PubMed:15834424). Interacts with RAD51AP1; the interaction is direct and stimulates DMC1-mediated homologous recombination (By similarity).|||In spermatocytes, shows punctate localization along chromosome axes specifically in early meiotic prophase I cells. Foci start to appear from the leptotene stage, reach their greatest number in the zygotene stage, in the early pachytene stage, the DMC1 foci mostly disappeared from autosomes and became restricted to the sex chromosomes.|||May participate in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.|||Nucleus|||Participates in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.|||Testis. http://togogenome.org/gene/10090:Brd7 ^@ http://purl.uniprot.org/uniprot/O88665 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase (By similarity). Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR.|||Chromosome|||Expressed ubiquitously from 10.5 to 18.5 dpc.|||Interacts with IRF2 and HNRPUL1 (By similarity). Interacts (via N-terminus) with TP53. Interacts (via C-terminus) with EP300. Interacts with BRCA1. Interacts (via bromo domain) with histone H3 (via N-terminus) acetylated at 'Lys-14' (H3K14ac). Has low affinity for histone H3 acetylated at 'Lys-9' (H3K9ac). Has the highest affinity for histone H3 that is acetylated both at 'Lys-9' (H3K9ac) and at 'Lys-14' (H3K14ac). Has very low affinity for non-acetylated histone H3. Interacts (via bromo domain) with histone H4 (via N-terminus) acetylated at 'Lys-8' (H3K8ac) (in vitro) (By similarity). Interacts with TRIM24, PTPN13 and DVL1. Identified in a complex with SMARCA4/BRG1, SMARCC1/BAF155, SMARCE1/BAF57, DPF2/BAF45D and ARID2, subunits of the SWI/SNF-B (PBAF) chromatin remodeling complex.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Rap2c ^@ http://purl.uniprot.org/uniprot/Q8BU31 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Ras family.|||Cytoplasm|||Palmitoylated. Palmitoylation is required for association with recycling endosome membranes and activation of TNIK.|||Recycling endosome membrane|||Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form. May play a role in cytoskeletal rearrangements and regulate cell spreading through activation of the effector TNIK. May play a role in SRE-mediated gene transcription. http://togogenome.org/gene/10090:Smarcal1 ^@ http://purl.uniprot.org/uniprot/Q8BJL0 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent annealing helicase that binds selectively to fork DNA relative to ssDNA or dsDNA and catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA. May play an important role in DNA damage response by acting at stalled replication forks (By similarity).|||Belongs to the SNF2/RAD54 helicase family. SMARCAL1 subfamily.|||DNA damage-regulated phosphorylation by kinases that may include ATM, ATR and PRKDC.|||Interacts with RPA2; the interaction is direct and mediates the recruitment by the RPA complex of SMARCAL1 to sites of DNA damage.|||May be due to an intron retention.|||Nucleus|||Ubiquitously expressed, with high levels in brain, heart, kidney, liver and testis. http://togogenome.org/gene/10090:Pfn2 ^@ http://purl.uniprot.org/uniprot/Q9JJV2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the profilin family.|||Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.|||Interacts with ACTMAP (via N-terminus); the interaction may facilitate efficient cleavage of the acetylated N-terminus of immature actin by ACTMAP.|||Isoform IIa is the main isoform and is abundant in brain. Isoform IIb is a minor isoform.|||Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio (By similarity). Interacts with PFN2 (PubMed:19403918).|||cytoskeleton http://togogenome.org/gene/10090:Clec11a ^@ http://purl.uniprot.org/uniprot/O88200 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Detected in femur where it localizes to trabecular bone of the femur metaphysis, and cortical bone of the proximal femur. Also expressed in trabecular and cortical bone of vertebrae (at protein level). Strongly expressed in osteoblasts and bone marrow stromal cells. Also has very weak expression in B cell progenitors in the bone marrow and T cells in the spleen.|||O-glycosylated. Probably sulfated on the O-glycans (By similarity).|||Promotes osteogenesis by stimulating the differentiation of mesenchymal progenitors into mature osteoblasts. Important for repair and maintenance of adult bone.|||Secreted|||Viable with no gross defects. Trabecular bone volume and bone mineral density is significantly reduced at two months of age, and progressively worsens with age. Bone strength is reduced and fracture healing is impaired. Hematopoiesis appears to be normal. http://togogenome.org/gene/10090:Sytl3 ^@ http://purl.uniprot.org/uniprot/Q99N48 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endomembrane system|||Highly expressed in spleen and lung. Detected at lower levels in heart and testis.|||May act as Rab effector protein and play a role in vesicle trafficking. Binds phospholipids in the presence of calcium ions.|||Monomer. Binds NRXN1. Binds RAB27A that has been activated by GTP-binding via its N-terminus. http://togogenome.org/gene/10090:Anapc1 ^@ http://purl.uniprot.org/uniprot/P53995 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Abundantly expressed in proliferating fibroblasts, juvenile testis, adult brain and epididymis.|||Belongs to the APC1 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Phosphorylated. Phosphorylation on Ser-355 occurs specifically during mitosis (By similarity).|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.|||Uniformly expressed throughout interphase of the cell cycle. http://togogenome.org/gene/10090:Alms1 ^@ http://purl.uniprot.org/uniprot/A0A1D5RMI8|||http://purl.uniprot.org/uniprot/Q8K4E0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ALMS1 family.|||Cytoplasm|||Expressed at 7.5 dpc. At 8.0 dpc expression is found in mesodermal- and ectodermal-derived layers. At 10.5 dpc mainly detected in midbrain, hindbrain, forelimb and hindlimb. Also expressed at 15.5 dpc and 18.5 dpc.|||Involved in PCM1-dependent intracellular transport. Required, directly or indirectly, for the localization of NCAPD2 to the proximal ends of centrioles. Required for proper formation and/or maintenance of primary cilia (PC), microtubule-based structures that protrude from the surface of epithelial cells (By similarity).|||Mice display obesity, hypogonadism, hyperinsulinemia, retinal dysfunction and hearing loss.|||Ubiquitously expressed.|||centrosome|||cilium basal body|||spindle pole http://togogenome.org/gene/10090:Pcdhgb5 ^@ http://purl.uniprot.org/uniprot/Q91XX5 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Rhd ^@ http://purl.uniprot.org/uniprot/A0A0R4J0A2|||http://purl.uniprot.org/uniprot/Q8CF94 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.|||Cell membrane|||May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane.|||Membrane|||Palmitoylated. http://togogenome.org/gene/10090:Gal3st2c ^@ http://purl.uniprot.org/uniprot/Q3ULK5 ^@ Similarity ^@ Belongs to the galactose-3-O-sulfotransferase family. http://togogenome.org/gene/10090:Xrcc3 ^@ http://purl.uniprot.org/uniprot/Q80W51|||http://purl.uniprot.org/uniprot/Q9CXE6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RecA family. RAD51 subfamily.|||Cytoplasm|||Interacts with RAD51C and RAD51. Part of the CX3 complex consisting of RAD51C and XRCC3; the complex has a ring-like structure arranged into a flat disc around a central channel; CX3 can interact with RAD51 in vitro. Forms a complex with FANCD2, BRCA2 and phosphorylated FANCG. Interacts with SWSAP1 and ZSWIM7; involved in homologous recombination repair. Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (By similarity).|||Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD21 paralog protein complex CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C (By similarity).|||Mitochondrion matrix|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Esx1 ^@ http://purl.uniprot.org/uniprot/A2AG22|||http://purl.uniprot.org/uniprot/O88933 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rnf207 ^@ http://purl.uniprot.org/uniprot/Q3V3A7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with the core-glycosylated, but not the fully glycosylated form of KCNH2/HERG. Interacts with DNAJA1 and HSPA8. Interacts (via the C-terminus) with HSPA1A; this interaction additively increases KCNH2 expression.|||Plays a role in cardiac repolarization possibly by stabilizing membrane expression of the potassium channel KCNH2/HERG, or by assisting its synthesis, folding or export from the endoplasmic reticulum, in a heat shock protein-dependent manner. http://togogenome.org/gene/10090:Dync1i2 ^@ http://purl.uniprot.org/uniprot/A2BFF5|||http://purl.uniprot.org/uniprot/A2BFF7|||http://purl.uniprot.org/uniprot/A2BFF8|||http://purl.uniprot.org/uniprot/A2BFF9|||http://purl.uniprot.org/uniprot/D6Q0F5|||http://purl.uniprot.org/uniprot/D6Q0F6|||http://purl.uniprot.org/uniprot/D6Q0F7|||http://purl.uniprot.org/uniprot/O88487|||http://purl.uniprot.org/uniprot/Q3TPJ8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (By similarity). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (By similarity). The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1 (PubMed:27474409). Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes (PubMed:27474409).|||Belongs to the dynein intermediate chain family.|||Cytoplasm|||Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition (By similarity). The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits (By similarity). The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer (By similarity). Interacts with DYNLT3 (By similarity). Interacts with DYNLT1 (By similarity). Interacts (dephosphorylated at Ser-84) with DCTN1 (PubMed:27474409). Interacts with BICD2 (PubMed:22956769). Interacts with SPEF2 (PubMed:28619825).|||Pyrophosphorylation by 5-diphosphoinositol pentakisphosphate (5-IP7) promotes interaction with DCTN1 (PubMed:27474409). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue (PubMed:27474409).|||The phosphorylation status of Ser-84 appears to be involved in dynactin-dependent target binding.|||cytoskeleton http://togogenome.org/gene/10090:Atp5g1 ^@ http://purl.uniprot.org/uniprot/Q9CR84 ^@ Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase C chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. A homomeric c-ring of probably 10 subunits is part of the complex rotary element (By similarity).|||Mitochondrion membrane|||There are three genes which encode the mitochondrial ATP synthase proteolipid and they specify precursors with different import sequences but identical mature proteins.|||This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).|||Trimethylated by ATPSCKMT at Lys-104. Methylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration. http://togogenome.org/gene/10090:Irak1 ^@ http://purl.uniprot.org/uniprot/Q62406 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.|||Cytoplasm|||Expressed from 11 dpc to 18 dpc.|||Following recruitment on the activated receptor complex, phosphorylated on Thr-209, probably by IRAK4, resulting in a conformational change of the kinase domain, allowing further phosphorylations to take place. Thr-387 phosphorylation in the activation loop is required to achieve full enzymatic activity (By similarity).|||Highly expressed in liver, followed by kidney and skeletal muscle.|||Homodimer (By similarity). Forms a complex with TRAF6, PELI1, IRAK4 and MYD88 (PubMed:16951688). Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression (By similarity). The TRAF6-PELI1-IRAK4-MYD88 complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation (By similarity). Interaction with MYD88 recruits IRAK1 to the stimulated receptor complex (By similarity). Interacts with TOLLIP; this interaction occurs in the cytosol prior to receptor activation (By similarity). Interacts with IL1RL1 (By similarity). Interacts (when polyubiquitinated) with IKBKG/NEMO (By similarity). Interacts with RSAD2/viperin (PubMed:21435586). Interacts with IRAK1BP1 (PubMed:11096118). Interacts with PELI2 (PubMed:12370331). Interacts with ZC3H12A; this interaction increases the interaction between ZC3H12A and IKBKB/IKKB (PubMed:22037600). Interacts with IRAK4 (By similarity). Interacts with PELI3 (By similarity). Interacts with PELI1 and TRAF6 (By similarity). Interacts with INAVA; the interaction takes place upon PRR stimulation (By similarity). Interacts (via C-terminus) with NFATC4 (via N-terminus) (By similarity).|||Lipid droplet|||Mice show a loss in TLR7- and TLR9-mediated IFN-alpha production in plasmacytoid dendritic cells demonstrating an important role in innate immune response.|||Nucleus|||Polyubiquitinated by TRAF6 after cell stimulation with IL-1-beta by PELI1, PELI2 and PELI3. Polyubiquitination occurs with polyubiquitin chains linked through 'Lys-63'. Ubiquitination promotes interaction with NEMO/IKBKG. Also sumoylated; leading to nuclear translocation (By similarity).|||Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3 (By similarity).|||The ProST region is composed of many proline and serine residues (more than 20 of each) and some threonines. This region is the site of IRAK-1 hyperphosphorylation (By similarity). http://togogenome.org/gene/10090:Bcl2a1a ^@ http://purl.uniprot.org/uniprot/Q07440 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Bcl-2 family.|||By granulocyte-macrophage colony-stimulating factor and LPS in macrophages.|||Cytoplasm|||Expressed in hemopoietic tissues, including bone marrow, spleen and thymus.|||Interacts directly with BCL2L11/BIM and PMAIP1 (By similarity). Interacts directly with BAK1, BID, BMF and BBC3. Interacts with BOP (By similarity). Interacts with isoform 3, isoform 4 and isoform 5 of ING4. Interacts with UBQLN4 (By similarity).|||Retards apoptosis induced by IL-3 deprivation. May function in the response of hemopoietic cells to external signals and in maintaining endothelial survival during infection. Can inhibit apoptosis induced by serum starvation in the mammary epithelial cell line HC11 (PubMed:11888890). http://togogenome.org/gene/10090:Cdca7l ^@ http://purl.uniprot.org/uniprot/Q922M5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in all tissues but not detected in total brain.|||Interacts with MYC (By similarity). Interacts (via IBM motifs) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (By similarity).|||Nucleus|||Phosphorylation increases its interaction with PSIP1.|||Plays a role in transcriptional regulation as a repressor that inhibits monoamine oxidase A (MAOA) activity and gene expression by binding to the promoter. Plays an important oncogenic role in mediating the full transforming effect of MYC in medulloblastoma cells (By similarity). Involved in apoptotic signaling pathways; May act downstream of P38-kinase and BCL-2, but upstream of CASP3/caspase-3 as well as CCND1/cyclin D1 and E2F1. http://togogenome.org/gene/10090:Or5d39 ^@ http://purl.uniprot.org/uniprot/Q7TR26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptgis ^@ http://purl.uniprot.org/uniprot/O35074 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Catalyzes the biosynthesis and metabolism of eicosanoids. Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2), a potent mediator of vasodilation and inhibitor of platelet aggregation. Additionally, displays dehydratase activity, toward hydroperoxyeicosatetraenoates (HPETEs), especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE).|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Postn ^@ http://purl.uniprot.org/uniprot/A0A097BW18|||http://purl.uniprot.org/uniprot/A0A097BW21|||http://purl.uniprot.org/uniprot/Q62009 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By TGF-beta (PubMed:11335131).|||Gamma-carboxylation is controversial. Gamma-carboxyglutamated; gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation; these residues may be required for binding to calcium (PubMed:18450759). According to a more recent report in human, does not contain vitamin K-dependent gamma-carboxyglutamate residues (By similarity).|||Golgi apparatus|||Homodimer (By similarity). Interacts with BMP1 and fibronectin (PubMed:20181949).|||In the heart, expressed from embryonic day 10.5. Continues to be strongly expressed throughout cardiac development and into adulthood (PubMed:11335131).|||Induces cell attachment and spreading and plays a role in cell adhesion (PubMed:10404027). Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic activation of lysyl oxidase LOX (PubMed:20181949).|||Preferentially expressed in periosteum and periodontal ligament (PubMed:10404027). Also expressed in the developing and adult heart (PubMed:11335131).|||Reduced amount of collagen cross-linking in femur and periosteum (PubMed:20181949).|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Vars ^@ http://purl.uniprot.org/uniprot/Q790I0|||http://purl.uniprot.org/uniprot/Q9Z1Q9 ^@ Activity Regulation|||Similarity|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Can be regulated by protein kinase C-dependent phosphorylation.|||Forms high-molecular-mass aggregates with elongation factor 1. http://togogenome.org/gene/10090:Reck ^@ http://purl.uniprot.org/uniprot/Q9Z0J1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RECK family.|||Cell membrane|||Embryonic lethality around 10.5 dpc, caused by reduced tissue integrity, arrested vasculogenesis and precocious neuronal differentiation (PubMed:11747814). Conditional knockout mice lacking Reck in endothelial cells show central nervous system (CNS) angiogenesis defects, characterized by moderate hemorrhages in the forebrain and vascular malformations in the cortex (PubMed:26658478, PubMed:28803732). Conditional deletion in endothelial cells also cause blood-brain barrier defects in neonates (PubMed:28803732). Phenotypes are caused by impaired beta-catenin-dependent signaling (PubMed:28803732).|||Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (PubMed:28803732). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (PubMed:26658478, PubMed:28803732). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7 (By similarity). ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex (By similarity). Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity (PubMed:11747814). Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP) (PubMed:11747814).|||In 10.5 dpc embryos, widely expressed in mesenchymal tissues and is relatively abundant in the marginal zone of the neural tube and large blood vessels such as the aorta.|||Interacts (via knot repeats) with WNT7A (via disordered linker region); the interaction is direct (By similarity). Interacts (via knot repeats) with WNT7B (via disordered linker region); the interaction is direct (By similarity). Interacts with ADGRA2; the interaction is direct (PubMed:28803732). Interacts with MMP9 (By similarity).|||The Kazal-like domains mediate the serine protease inhibitor activity. http://togogenome.org/gene/10090:Pomgnt2 ^@ http://purl.uniprot.org/uniprot/Q8BW41 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 61 family.|||Endoplasmic reticulum membrane|||Expressed during brain development. At 14.5 dpc, expressed throughout the cortical plate and the developing brain, as well as throughout the eye, including the lens and cornea. Cortical expression is already detected at 12.5 dpc, peaks between 14.5 and 16.5 dpc and is reduced at birth.|||Mainly expressed in the central nervous system.|||Newborns are slightly smaller and die within the first day of birth due to abnormal basal lamina formation and neuronal migration defects. Defects are due to a lack of laminin-binding glycans.|||O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein (By similarity). Involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:24256719). http://togogenome.org/gene/10090:Ptgdr ^@ http://purl.uniprot.org/uniprot/P70263 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Most abundantly expressed in the ileum, followed by lung, stomach and uterus.|||Mutant mice show decreased susceptibility to passive cutaneous anaphylaxis associated with decreased mast cell degranulation.|||Receptor for prostaglandin D2 (PGD2). The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobilization of calcium is also observed, but without formation of inositol 1,4,5-trisphosphate (By similarity). Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by immature mast cells and acts on nearby fibroblasts upstream to PTDGS to synthesize PGD2, which in turn promotes mast cell maturation and degranulation via PTGDR (PubMed:23624557). http://togogenome.org/gene/10090:Wscd1 ^@ http://purl.uniprot.org/uniprot/Q80XH4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WSCD family.|||Golgi apparatus membrane|||Sialate:O-sulfotransferase which catalyzes 8-O-sulfation at the Sia-glycan level using 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a donor, forming 8-O-sulfated Sia (Sia8S)-glycans. http://togogenome.org/gene/10090:Or52n4 ^@ http://purl.uniprot.org/uniprot/Q8VGV5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or2n1d ^@ http://purl.uniprot.org/uniprot/Q8VG72 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cldn15 ^@ http://purl.uniprot.org/uniprot/Q9Z0S5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Can form linear homooligomers in the membrane, giving rise to tight junction strand-like structures.|||Cell membrane|||Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members function as impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN15 forms tight junctions that mediate the paracellular transport of small monovalent cations along a concentration gradient, due to selective permeability for Na(+), Li(+) and K(+) ions, but selects against Cl(-) ions. Plays an important role in paracellular Na(+) transport in the intestine and in Na(+) homeostasis. Required for normal Na(+)-dependent intestinal nutrient uptake.|||Detected in duodenum, jejunum and ileum. Detected on intestinal villi and crypts (at protein level). Ubiquitous. Detected in small intestine, colon, jejunum, heart, kidney and lung.|||No visible phenotype at birth and during the first four weeks after birth. After about eight weeks, the upper part of the small intestine is abnormally increased both in length and in thickness with enlarged villi and crypts. The villi are about two times larger than normal, and each is associated with about forty abnormally large crypts instead of the normally observed ratio of ten crypts per villus. In contrast, there is no difference in the size of the lower part of the small intestine. The body weight of mutant mice does not differ from that of wild-type littermates (PubMed:18242218). According to PubMed:20727355, the intestinal mucosa from newborn and adult mutant mice displays strongly decreased transepithelial conductance with strongly reduced paracellular Na(+) permeability, but no major changes in paracellular permeability to Cl(-). Adults show strongly decreased Na(+) levels in the lumen of the small intestine. Mutant mice also display decreased intestinal glucose uptake, probably due to decreased Na(+) levels. According to PubMed:23089202, mutant mice lacking both Cldn2 and Cldn15 display no visible phenotype at birth, but show decreased growth after about 10 days, severe developmental retardation about 14 days after birth, and then die from malnutrition. None survive more than 25 days after birth. Mice lacking both Cldn2 and Cldn15 show abnormally low Na(+) levels in the intestine, leading to decreased intestinal glucose uptake; glucose uptake can be restored to normal levels by addition of Na(+). Likewise, mice lacking both Cldn2 and Cldn15 show decreased intestinal uptake of milk fat, fatty acids, bile acids and amino acids; again, normal bile acid and amino acid uptake can be restored by the addition of Na(+).|||Palmitoylated when heterogeneously expressed in S.frugiperda cells.|||tight junction http://togogenome.org/gene/10090:Sec11a ^@ http://purl.uniprot.org/uniprot/Q9R0P6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S26B family.|||Catalytic component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. Specifically cleaves N-terminal signal peptides that contain a hydrophobic alpha-helix (h-region) shorter than 18-20 amino acids.|||Component of the signal peptidase complex paralog A (SPC-A) composed of a catalytic subunit SEC11A and three accessory subunits SPCS1, SPCS2 and SPCS3. Within the complex, interacts with SPCS2 and SPCS3. The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids.|||Endoplasmic reticulum membrane|||The C-terminal short (CTS) helix is essential for catalytic activity. It may be accommodated as a transmembrane helix in the thinned membrane environment of the complex, similarly to the signal peptide in the complex substrates. http://togogenome.org/gene/10090:Or6z1 ^@ http://purl.uniprot.org/uniprot/Q8VGH3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wdr37 ^@ http://purl.uniprot.org/uniprot/Q8CBE3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Forms homodimers (By similarity). Interacts with PACS1 (PubMed:33630350). Interacts with PACS2 (By similarity).|||Mice lacking WDR37 have reduced absolute numbers of circulating T and B lymphocytes.|||Nucleus|||Required for normal ER Ca2+ handling in lymphocytes. Together with PACS1, it plays an essential role in stabilizing peripheral lymphocyte populations. http://togogenome.org/gene/10090:Evc2 ^@ http://purl.uniprot.org/uniprot/Q8K1G2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Component of the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE (PubMed:24582806). Interacts with EVC (PubMed:21356043, PubMed:24582806). Interacts (via N-terminal end) with EFCAB7 (PubMed:24582806). Interacts (via N-terminal end) with IQCE (PubMed:24582806).|||Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling (PubMed:21356043, PubMed:24582806). Plays a critical role in bone formation and skeletal development (PubMed:21356043). May be involved in early embryonic morphogenesis (PubMed:21356043).|||Expressed in long and cranial bones, kidney and heart. Strongly expressed in proliferating chondrocytes, osteoblasts and osteoclasts.|||Found in the embryo at day 7 dpc, 11 dpc, 15 dpc, and 17 dpc. At the limb bud formation stage 11 dpc, it is expressed in fore- and hindlimb buds, branchial arches, and facial primordia.|||Nucleus|||cilium|||cilium basal body|||cilium membrane http://togogenome.org/gene/10090:Mtor ^@ http://purl.uniprot.org/uniprot/Q9JLN9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylates when part of mTORC1 or mTORC2 (By similarity). Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation (PubMed:19487463). Phosphorylation in the kinase domain modulates the interactions of MTOR with RPTOR and AKT1S1/PRAS40 and leads to increased intrinsic mTORC1 kinase activity (By similarity). Phosphorylation at Ser-2159 by TBK1 in response to growth factors and pathogen recognition receptors promotes mTORC1 activity (PubMed:29150432). Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity (By similarity).|||Belongs to the PI3/PI4-kinase family.|||Cytoplasm|||Early embryonic lethality (PubMed:15485918). Embryonic development stops at 5.5 dpc and embryos are severely runted and display an aberrant developmental phenotype (PubMed:15485918). Embryos are able to implant due to a maternal mRNA contribution, which persists during preimplantation development (PubMed:15485918). Embryos display a lesion in inner cell mass proliferation, due to the inability to establish embryonic stem cells (PubMed:15485918).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Lysosome membrane|||Microsome membrane|||Mitochondrion outer membrane|||Nucleus|||PML body|||Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR (PubMed:20801936). The mTORC1 complex is a 1 Md obligate dimer of two stoichiometric heterotetramers with overall dimensions of 290 A x 210 A x 135 A (By similarity). It has a rhomboid shape and a central cavity, the dimeric interfaces are formed by interlocking interactions between the two MTOR and the two RPTOR subunits (By similarity). The MLST8 subunit forms distal foot-like protuberances, and contacts only one MTOR within the complex, while the small AKT1S1/PRAS40 localizes to the midsection of the central core, in close proximity to RPTOR (By similarity). mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity by blocking MTOR substrate-recruitment site (By similarity). Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15467718, PubMed:16962653). Interacts with PLPP7 and PML (PubMed:16915281, PubMed:19704009). Interacts with PRR5 and RICTOR; the interaction is direct within the mTORC2 complex and interaction with RICTOR is enhanced by deubiquitination of RICTOR by USP9X (PubMed:20801936). mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity (By similarity). Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation (By similarity). Interacts with UBQLN1 (By similarity). Interacts with TTI1 and TELO2 (By similarity). Interacts with CLIP1; phosphorylates and regulates CLIP1 (By similarity). Interacts with NBN (By similarity). Interacts with HTR6 (PubMed:23027611). Interacts with BRAT1 (By similarity). Interacts with MEAK7 (via C-terminal domain); the interaction increases upon nutrient stimulation (By similarity). Interacts with TM4SF5; the interaction is positively regulated by arginine and is negatively regulated by leucine (By similarity). Interacts with GPR137B (By similarity). Interacts with NCKAP1L (By similarity). Interacts with TPCN1 and TPCN2; the interaction is required for TPCN1 and TPCN2 sensitivity to ATP (By similarity). Interacts with ATP6V1A and with CRYAB, forming a ternary complex (PubMed:31786107). Interacts with SLC38A7; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation (By similarity).|||Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:15467718, PubMed:15545625, PubMed:15485918, PubMed:16221682, PubMed:16915281, PubMed:16962653, PubMed:18046414, PubMed:19440205, PubMed:21659604). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15467718, PubMed:15545625, PubMed:16221682, PubMed:16915281, PubMed:16962653, PubMed:18046414, PubMed:19440205, PubMed:21659604). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15467718, PubMed:16962653, PubMed:21659604). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:15485918). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:15485918). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:15485918). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (By similarity). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (By similarity). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (By similarity). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:11792863). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (PubMed:18046414). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:21258367). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:21258367). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (By similarity). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (By similarity). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (By similarity). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (By similarity). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (By similarity). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:27913603). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:27913603). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (PubMed:19346248). As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. mTORC2 plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (By similarity). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (PubMed:19440205). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (PubMed:29750810). Phosphorylates SQSTM1, promoting interaction between SQSTM1 and KEAP1 and subsequent inactivation of the BCR(KEAP1) complex (PubMed:24011591).|||The FAT domain forms three discontinuous subdomains of alpha-helical TPR repeats plus a single subdomain of HEAT repeats. The four domains pack sequentially to form a C-shaped a-solenoid that clamps onto the kinase domain (By similarity).|||The kinase domain (PI3K/PI4K) is intrinsically active but has a highly restricted catalytic center.|||The mTORC1 complex is activated in response to nutrients, growth factors or amino acids: activation requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD (By similarity). Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1 (By similarity). Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1 (PubMed:19487463). On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1 (PubMed:15545625). The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 (By similarity). The kinase activity of MTOR is inhibited by DEPTOR and AKT1S1 (By similarity). The non-canonical mTORC1 complex is independent of the RHEB GTPase and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 but not other mTORC1 substrates: it is activated by FLCN, which activates Rag GTPases RagC/RRAGC and RagD/RRAGD (By similarity). MTOR is the target of the immunosuppressive and anti-cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and specifically inhibits its kinase activity (PubMed:7809080). mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (By similarity). mTORC2 may also be regulated by RHEB but in an indirect manner through the PI3K signaling pathway (By similarity).|||phagosome http://togogenome.org/gene/10090:Or5p78 ^@ http://purl.uniprot.org/uniprot/Q7TRU6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ksr2 ^@ http://purl.uniprot.org/uniprot/Q3UVC0 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cytoplasm|||Heterodimerizes (via N-terminus) with BRAF (via N-terminus) in a MAP2K1/MEK1-dependent manner. Interacts with BRAF; this increases the low intrinsic protein kinase activity of KSR2. Interacts with MAP2K1, forming a heterodimer that can dimerize to form a heterotetramer. Interacts with MAP3K8, MAPK, RAS and RAF.|||Location-regulated scaffold connecting MEK to RAF. Has very low protein kinase activity and can phosphorylate MAP2K1 at several Ser and Thr residues with very low efficiency (in vitro). Acts as MAP2K1/MEK1-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1. Interaction with BRAF enhances KSR2-mediated phosphorylation of MAP2K1 (in vitro). Blocks MAP3K8 kinase activity and MAP3K8-mediated signaling. Acts as a negative regulator of MAP3K3-mediated activation of ERK, JNK and NF-kappa-B pathways, inhibiting MAP3K3-mediated interleukin-8 production.|||Membrane|||Phosphorylated on Ser-475 by MARK3.|||The protein kinase domain is predicted to be catalytically inactive and seems to have very low intrinsic kinase activity. This low kinase activity can be increased by interaction with BRAF (By similarity). http://togogenome.org/gene/10090:Sun5 ^@ http://purl.uniprot.org/uniprot/Q9DA32 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Golgi apparatus|||Highly glycosylated in the Golgi apparatus during spermiogenesis.|||Mutant males are infertile. Spermatozoa are acephalic, the sperm head to tail coupling apparatus is detached from nucleus during spermatid elongation.|||Nucleus inner membrane|||Observed in spermatocyte meiosis I and II stages (PubMed:21711156). Expressed during spermiogenesis (PubMed:29298896).|||Plays an essential role in anchoring sperm head to the tail. Is responsible for the attachment of the coupling apparatus to the sperm nuclear envelope.|||Probable homotrimer (Probable). Interacts with DNAJB13 (PubMed:29298896).|||Testis-specific, abundantly expressed in spermatocytes and round spermatids. http://togogenome.org/gene/10090:Cyth2 ^@ http://purl.uniprot.org/uniprot/P63034 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a guanine-nucleotide exchange factor (GEF). Promotes guanine-nucleotide exchange on ARF1, ARF3 and ARF6. Activates ARF factors through replacement of GDP with GTP (PubMed:18042453). The cell membrane form, in association with ARL4 proteins, recruits ARF6 to the plasma membrane (By similarity). Involved in neurite growth (PubMed:25326380).|||Autoinhibited by its C-terminal basic region.|||Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate. The PH domain is necessary and sufficient for plasma membrane relocalization (By similarity).|||Cell membrane|||Cell projection|||Cytoplasm|||Heteromer. Composed of TAMALIN, CYTH2 and at least one GRM1. Interacts with ARRB1. Interacts with ARL4D; the interaction is direct (By similarity). Directly interacts with CCDC120 through the coiled coil domain; this interaction stabilizes CCDC120, possibly by preventing its ubiquitination, and is required for neurite growth in a neuroblastoma cell line (PubMed:25326380). Interacts with FRMD4A (PubMed:20080746). Interacts (via N-terminal domain) with INAVA (via N-terminal domain) (By similarity).|||Present in all tissues tested, with highest protein levels in brain and adrenal.|||The coiled coil domain is involved in interaction with CCDC120.|||Up-regulated in differentiating neuroblastoma cells.|||adherens junction|||growth cone|||tight junction http://togogenome.org/gene/10090:Snph ^@ http://purl.uniprot.org/uniprot/Q80U23 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds to syntaxin-1.|||Inhibits SNARE complex formation by absorbing free syntaxin-1.|||Membrane|||synaptosome http://togogenome.org/gene/10090:Grb14 ^@ http://purl.uniprot.org/uniprot/A2ASX2|||http://purl.uniprot.org/uniprot/Q9JLM9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein which modulates coupling of cell surface receptor kinases with specific signaling pathways. Binds to, and suppresses signals from, the activated insulin receptor (INSR). Potent inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical role regulating PDPK1 membrane translocation in response to insulin stimulation and serves as an adapter protein to recruit PDPK1 to activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and transduction of the insulin signal (By similarity).|||Belongs to the GRB7/10/14 family.|||Cytoplasm|||Endosome membrane|||Interacts with the cytoplasmic domain of the autophosphorylated insulin receptor, through the SH2 domain. Interacts with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop on INSR from dephosphorylation (By similarity). Binds to the ankyrin repeat region of TNKS2 via its N-terminus. Interacts with activated NRAS (By similarity). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated).|||Phosphorylated on serine residues. Phosphorylated on tyrosine residues by TEK/TIE2 (By similarity).|||The PH domain binds relatively non-specifically and with low affinity to several phosphoinositides, the best binder being PI(3,4,5)P3. http://togogenome.org/gene/10090:Usp11 ^@ http://purl.uniprot.org/uniprot/Q99K46 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Chromosome|||Cytoplasm|||Monomer (By similarity). Associated component of the Polycomb group (PcG) multiprotein PRC1-like complex (By similarity). Interacts with RANBP9/RANBPM (By similarity). Interacts with BRCA2 (By similarity). Interacts with CHUK/IKKA (By similarity). Interacts with NFKBIA (By similarity). Interacts with SPRY3, RAE1, MYCBP2/PAM, and KCTD6 (By similarity).|||Nucleus|||Protease that can remove conjugated ubiquitin from target proteins and polyubiquitin chains. Inhibits the degradation of target proteins by the proteasome. Cleaves preferentially 'Lys-6' and 'Lys-63'-linked ubiquitin chains. Has lower activity with 'Lys-11' and 'Lys-33'-linked ubiquitin chains, and extremely low activity with 'Lys-27', 'Lys-29' and 'Lys-48'-linked ubiquitin chains (in vitro). Plays a role in the regulation of pathways leading to NF-kappa-B activation. Plays a role in the regulation of DNA repair after double-stranded DNA breaks. Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex. Promotes cell proliferation by deubiquitinating phosphorylated E2F1. http://togogenome.org/gene/10090:Tmem200a ^@ http://purl.uniprot.org/uniprot/B2RUN2|||http://purl.uniprot.org/uniprot/Q8C817 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM200 family.|||Membrane http://togogenome.org/gene/10090:Arhgef19 ^@ http://purl.uniprot.org/uniprot/Q8BWA8 ^@ Function|||Tissue Specificity ^@ Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase.|||Highly expressed in intestine, and at lower levels in liver, heart and kidney. http://togogenome.org/gene/10090:Duoxa1 ^@ http://purl.uniprot.org/uniprot/Q8VE49 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DUOXA family.|||May be required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX1.|||May interact with NUMB.|||Membrane http://togogenome.org/gene/10090:Tuft1 ^@ http://purl.uniprot.org/uniprot/O08970 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ameloblasts, and also non-odontogenic tissues including kidney, lung, liver and testis.|||Belongs to the tuftelin family.|||Expressed in tooth from 13 dpc, the bud stage. Continues to be expressed even when thick enamel is formed.|||Interacts with TFIP11. May form oligomers.|||Involved in the mineralization and structural organization of enamel.|||Secreted http://togogenome.org/gene/10090:Or6c74 ^@ http://purl.uniprot.org/uniprot/Q8VG45 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nusap1 ^@ http://purl.uniprot.org/uniprot/Q9ERH4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NUSAP family.|||Chromosome|||Cytoplasm|||Expression peaks at G2/M phase and is low in G1 phase. Expressed at higher levels in immature erythroblasts relative to mature erythroblasts.|||Interacts with DNA and microtubules. Microtubule bundling is inhibited by IPO7, KPNA2 and KPNB1 while association with DNA is also inhibited by IPO7 and KPNA2.|||Microtubule-associated protein with the capacity to bundle and stabilize microtubules. May associate with chromosomes and promote the organization of mitotic spindle microtubules around them.|||The KEN box is required for the FZR1-dependent degradation of this protein subsequent to ubiquitination.|||Ubiquitinated. Ubiquitination by FZR1 may lead to proteasome-dependent degradation of this protein (By similarity).|||nucleolus|||spindle http://togogenome.org/gene/10090:Plekha3 ^@ http://purl.uniprot.org/uniprot/Q9ERS4 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with GTP-bound ARF1 (By similarity). Interacts with SACM1L and VAPA and/or VAPB to form a ternary complex (By similarity).|||Plays a role in regulation of vesicular cargo transport from the trans-Golgi network (TGN) to the plasma membrane (By similarity). Regulates Golgi phosphatidylinositol 4-phosphate (PtdIns(4)P) levels and activates the PtdIns(4)P phosphatase activity of SACM1L when it binds PtdIns(4)P in 'trans' configuration (By similarity). Binds preferentially to PtdIns(4)P (By similarity). Negatively regulates APOB secretion from hepatocytes (By similarity).|||The PH domain binds the small GTPase ARF1 and phosphatidylinositol-4-phosphate (PtdIns4P) with high selectivity, and is required for its recruitment to the trans-Golgi network (TGN).|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ly75 ^@ http://purl.uniprot.org/uniprot/Q60767 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an endocytic receptor to direct captured antigens from the extracellular space to a specialized antigen-processing compartment. Causes reduced proliferation of B lymphocytes (By similarity).|||Expressed in dendritic and thymic epithelial cells and lymph nodes.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Catsperd ^@ http://purl.uniprot.org/uniprot/E9Q9F6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation (PubMed:34225353). Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization (PubMed:21224844). Required for CATSPER1 stability before intraflagellar transport and/or incorporation of the CatSper complex channel into the flagellar membrane (PubMed:21224844).|||Belongs to the CATSPERD family.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:21224844, PubMed:34998468). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (PubMed:34225353).|||Expressed in spermatocytes and spermatids in different stages of spermatogenesis (at protein level).|||Mice are normal but males are sterile. Male sterility is due to defects in sperm cell hyperactivation and decreased stability of Catsper1.|||Testis-specific.|||flagellum membrane http://togogenome.org/gene/10090:Cep76 ^@ http://purl.uniprot.org/uniprot/Q0VEJ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP76 family.|||Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication (By similarity).|||Interacts with CCP110 and CEP97.|||centriole|||centrosome http://togogenome.org/gene/10090:Cgas ^@ http://purl.uniprot.org/uniprot/Q8C6L5 ^@ Activity Regulation|||Caution|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-372, Lys-382 and Lys-402 inhibits the cyclic GMP-AMP synthase activity. Deacetylated upon cytosolic DNA challenge such as viral infections. Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation.|||Belongs to the mab-21 family.|||Binds 1 Mg(2+) per subunit (PubMed:23647843). Is also active with Mn(2+) (PubMed:23647843, PubMed:32814054). Mn(2+)-activated enzyme forms an inverted pppGp(2'-5')A intermediate, suggesting a non-canonical but accelerated 2',3'-cGAMP cyclization without substrate flip-over (PubMed:32814054). Mn(2+) ions are coordinated by triphosphate moiety of the inverted substrate, independent of the catalytic triad residues (PubMed:32814054).|||Cell membrane|||Chromosome|||Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes CGAS recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagic degradation.|||Monomer in the absence of DNA (PubMed:28214358). Homodimer in presence of dsDNA: forms a 2:2 dimer with two enzymes binding to two DNA molecules (PubMed:29426904, PubMed:28902841). Interacts with nucleosomes; interaction is mainly mediated via histones H2A and H2B and inactivates the nucleotidyltransferase activity by blocking DNA-binding and subsequent activation (PubMed:32911481, PubMed:32911480, PubMed:32913000). Interacts with PQBP1 (via WW domain) (By similarity). Interacts with TRIM14; this interaction recruits USP14, leading to deubiquitinate and stabilize CGAS and promote type I interferon production (By similarity). Interacts with ZCCHC3; promoting sensing of dsDNA by CGAS (By similarity). Interacts (when not monomethylated) with (poly-ADP-ribosylated) PARP1; interaction takes place in the nucleus and prevents the formation of the PARP1-TIMELESS complex (PubMed:35210392). Interacts (when monomethylated) with SGF29; interaction with SGF29 prevents interaction with PARP1 (PubMed:35210392). Interacts with PCBP2; preventing the formation of liquid-like droplets in which CGAS is activated (By similarity). Interacts with Irgm1; promoting CGAS degradation (By similarity).|||Monomethylated at Lys-491 by SETD7 (PubMed:35210392). Monomethylation promotes interaction with SGF29, preventing interaction between PARP1 nad SGF29 (PubMed:35210392). Demethylation by RIOX1 promotes interaction with PARP1, followed by PARP1 inactivation (PubMed:35210392).|||Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23647843, PubMed:23722158, PubMed:26829768, PubMed:28214358, PubMed:29625897, PubMed:29426904, PubMed:32814054). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:23258413, PubMed:23647843, PubMed:23722158, PubMed:26829768, PubMed:28214358). Acts as a key DNA sensor: directly binds double-stranded DNA (dsDNA), inducing the formation of liquid-like droplets in which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates STING1, thereby triggering type-I interferon production (PubMed:23722158, PubMed:28314590, PubMed:28363908, PubMed:28095500). Preferentially binds long dsDNA (around 45 bp) and forms ladder-like networks that function cooperatively to stabilize individual cGAS-dsDNA complexes (PubMed:28902841). Acts as a key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:23722158, PubMed:28314590, PubMed:28363908). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:23258413, PubMed:23722158, PubMed:23647843). Also acts as an innate immune sensor of infection by retroviruses by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (By similarity). Also detects the presence of DNA from bacteria (By similarity). 2',3'-cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote STING1 activation and convey immune response to connecting cells (PubMed:24077100). 2',3'-cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but STING1-dependent manner (PubMed:26229117). Also senses the presence of neutrophil extracellular traps (NETs) that are translocated to the cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP (PubMed:33688080). In addition to foreign DNA, can also be activated by endogenous nuclear or mitochondrial DNA (By similarity). When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, DNA damage, mitotic arrest or senescence), or is present in form of cytosolic micronuclei, CGAS is activated leading to a state of sterile inflammation (PubMed:28738408, PubMed:28759028). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via STING1 and promote cellular senescence (PubMed:28759028). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability (PubMed:28738408). Micronuclei, which as frequently found in cancer cells, consist of chromatin surrounded by its own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to 2',3'-cGAMP synthesis and subsequent activation of STING1 and type-I interferon production (PubMed:28738408). In a healthy cell, CGAS is however kept inactive even in cellular events that directly expose it to self-DNA, such as mitosis, when cGAS associates with chromatin directly after nuclear envelope breakdown or remains in the form of postmitotic persistent nuclear cGAS pools bound to chromatin (By similarity). Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity (PubMed:31808743, PubMed:32911481, PubMed:32911480, PubMed:32913000). Also acts as a suppressor of DNA repair in response to DNA damage: inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214, PubMed:31544964, PubMed:35210392). In addition to DNA, also sense translation stress: in response to translation stress, translocates to the cytosol and associates with collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity).|||Nucleus|||Palmitoylation at Cys-459 by ZDHHC18 impairs DNA-binding, thereby preventing the cyclic GMP-AMP synthase activity.|||Poly-ADP-ribosylation at Glu-176 by PARP1 impairs DNA-binding, thereby preventing the cyclic GMP-AMP synthase activity.|||Polyglutamylated by TTLL6 at Glu-272, leading to impair DNA-binding activity. Monoglutamylated at Glu-302 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.|||Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation (PubMed:25525874, PubMed:30878284). The damage of the nucleus and the mitochondria during apoptosis leads to leakage of nuclear and mitochondrial DNA, which activate CGAS: cleavage and inactivation during apoptosis in required to prevent cytokine overproduction (PubMed:25525874). Cleaved by CASP7 and CASP3 during virus-induced apoptosis, thereby inactivating it and preventing cytokine overproduction (PubMed:30878284). Cleaved by CASP1 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 during non-canonical inflammasome activation; does not cut at the same sites than CASP1 (PubMed:28314590).|||Sumoylated at Lys-217 and Lys-464 by TRIM38 in uninfected cells and during the early phase of viral infection, promoting its stability by preventing ubiquitination at Lys-271 and Lys-464, and subsequent degradation (PubMed:27637147). Desumoylated by SENP2 during the late phase of viral infection (PubMed:27637147). Sumoylation at Lys-335, Lys-372 and Lys-382 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (PubMed:28095500). Desumoylation at Lys-335, Lys-372 and Lys-382 by SENP7 relieves inhibition and activates CGAS (PubMed:28095500).|||The N-terminal disordered part (1-146) binds unspecifically dsDNA and expand the binding and moving range of CGAS on dsDNA (PubMed:28214358, PubMed:28314590, PubMed:28363908). The disordered and positively charged residues enhance CGAS-DNA phase separation by increasing the valencies of DNA-binding (By similarity). The N-terminus is required to sense chromatin and its phosphorylation blocks its activation by chromatin DNA (By similarity). When the N-terminal part (1-146) is missing the protein bound to dsDNA homodimerizes (PubMed:28214358).|||The N-terminal disordered part (1-146) is phosphorylated by AURKB during the G2-M transition, blocking CGAS liquid phase separation and preventing activation (By similarity). Phosphorylation at Tyr-201 by BLK promotes cytosolic retention (By similarity). Localizes into the nucleus following dephosphorylation at Tyr-201 (By similarity). Phosphorylation at Ser-420 activates the nucleotidyltransferase activity (PubMed:32474700). Dephosphorylation at Ser-420 by PPP6C impairs its ability to bind GTP, thereby inactivating it (PubMed:32474700). Phosphorylation at Thr-52 and Ser-199 by PRKDC inhibits its cyclic GMP-AMP synthase activity by impairing homodimerization and activation (By similarity). Phosphorylation at Ser-291 by AKT (AKT1, AKT2 or AKT3) suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-291 by CDK1 during mitosis leads to its inhibition, thereby preventing CGAS activation by self-DNA during mitosis (PubMed:32351706). Dephosphorylated at Ser-291 by protein phosphatase PP1 upon mitotic exit (PubMed:32351706).|||The arginine-anchor tightly binds to the canonical H2A acidic-patch residues.|||The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA (By similarity). DNA-binding induces the formation of liquid-like droplets in which CGAS is activated (By similarity). Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (By similarity). A number of mechanisms exist to restrict its activity toward self-DNA (PubMed:32911481, PubMed:32911480, PubMed:32913000). The nucleotidyltransferase activity is inhibited in the nucleus via its association with nucleosomes: interacts with the acidic patch of histones H2A and H2B, thereby blocking DNA-binding and subsequent activation (PubMed:32156810, PubMed:32911481, PubMed:32911480, PubMed:32913000). CGAS is also inactive when associated with mitotic chromatin (By similarity). Chromatin-bound CGAS cannot be activated by exogenous DNA in mitotic cells: phosphorylation of the N-terminal disordered part by AURKB during the G2-M transition blocks CGAS liquid phase separation and activation (By similarity). Activity toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-binding, thereby preventing CGAS activation (PubMed:32156810). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation (By similarity). Acetylation at Lys-372, Lys-382 and Lys-402 inhibits the cyclic GMP-AMP synthase activity (By similarity). Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (By similarity). Phosphorylation at Ser-291 suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-420 promotes the cyclic GMP-AMP synthase activity (PubMed:32474700). Phosphorylation at Thr-52 and Ser-199 inhibits its cyclic GMP-AMP synthase activity (By similarity). Ubiquitination at Lys-372 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-335 promotes oligomerization and subsequent activation (PubMed:29426904). Sumoylation at Lys-335, Lys-372 and Lys-382 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (PubMed:28095500). The enzyme activity is impaired by the cleavage by CASP1 (PubMed:28314590). In addition to DNA, also activated by collided ribosomes upon translation stress: specifically binds collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity). In hematopoietic stem cells, binding to circular RNA cia-cGAS inhibits the cyclic GMP-AMP synthase activity (PubMed:29625897). Strongly inhibited by compound RU.521, which is specific for mouse protein (PubMed:28963528, PubMed:30007416).|||Ubiquitinated at Lys-402 via 'Lys-48'-linked polyubiquitin chains, leading to its SQSTM1-mediated autophagic degradation (By similarity). Interaction with TRIM14 promotes recruitment of USP14, leading to deubiquitinate Lys-402 and stabilize CGAS (By similarity). Ubiquitinated at Lys-372 by RNF185 via 'Lys-27'-linked polyubiquitination, promoting CGAS cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-335 by TRIM56 promotes oligomerization and subsequent activation (PubMed:29426904). Monoubiquitination by TRIM41 promotes CGAS activation (By similarity). Ubiquitination at Lys-271 and Lys-464 via 'Lys-48'-linked polyubiquitination promotes its degradation (PubMed:32457395, PubMed:27637147). Deubiquitination at Lys-271 by USP29 promotes its stabilization (PubMed:32457395). Deubiquitinated by USP27X, promoting its stabilization (PubMed:31534008). Ubiquitinated at Lys-399 via 'Lys-63'-linked polyubiquitin chains by MARCHF8, leading to the inhibition of its DNA binding ability (By similarity).|||Undergoes a liquid-like phase transition after binding to DNA, which is dependent on zinc.|||Was reported to homodimerize in presence of double-stranded DNA (dsDNA) (PubMed:24332030). However, this result was based on a structure lacking the N-terminal part (1-146), which caused homodimerization in presence of dsDNA (PubMed:28214358).|||cytosol http://togogenome.org/gene/10090:Mitd1 ^@ http://purl.uniprot.org/uniprot/Q8VDV8 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Interacts (via MIT domain) with CHMP1A, CHMP1B, CHMP2A and IST1 (By similarity).|||Late endosome membrane|||Membrane|||Midbody|||Required for efficient abscission at the end of cytokinesis, together with components of the ESCRT-III complex.|||The C-terminal domain interacts with lipid membranes containing acidic phosphoinositides and is required for location at the midbody.|||The MIT domain interacts with the MIT-interacting motifs of several components of the ESCRT-III complex. http://togogenome.org/gene/10090:Hells ^@ http://purl.uniprot.org/uniprot/Q60848 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||By concanavalin or lipopolysaccharide in unactivated splenocytes.|||Differentially expressed during embryonic development, with highest expression in developing face, limbs, skeletal muscle, heart, and tail. Highly expressed in fetal thymocytes from day 14 to 16 of gestation, and expressed at much lower levels in adult thymus.|||Highly expressed in thymus, bone marrow, and testis. Not detected in heart, brain, liver, kidney, skeletal muscle, spleen, peripheral blood lymphocytes, small intestine, colon, prostate or ovary.|||Nucleus|||Plays an essential role in normal development and survival. Involved in regulation of the expansion or survival of lymphoid cells. Required for de novo or maintenance DNA methylation. May control silencing of the imprinted CDKN1C gene through DNA methylation. May play a role in formation and organization of heterochromatin, implying a functional role in the regulation of transcription and mitosis. http://togogenome.org/gene/10090:Or56a4 ^@ http://purl.uniprot.org/uniprot/Q7TRN8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cul3 ^@ http://purl.uniprot.org/uniprot/Q9JLV5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cullin family.|||Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (By similarity). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (By similarity). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component (By similarity). BCR(KLHL42) is involved in ubiquitination of KATNA1 (By similarity). BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3 (By similarity). Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity (By similarity). BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis (By similarity). BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (By similarity). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (By similarity). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (By similarity). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (By similarity). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (By similarity). The BCR(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:34491895). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (By similarity). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition (By similarity). Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (By similarity). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM (By similarity). The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (By similarity). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (By similarity). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (By similarity). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:12193649, PubMed:14764894, PubMed:15282312). As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1. By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (By similarity).|||Cytoplasm|||Forms neddylation-dependent homodimers (By similarity). Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit (By similarity). The BCR complex may be active as a heterodimeric complex, in which NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule (By similarity). Interacts with RBX1, RNF7 and TIP120A/CAND1 (By similarity). Part of the BCR(SPOP) containing SPOP, and of BCR containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL (By similarity). Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13 (By similarity). Part of the BCR(KLHL41) complex containing KLHL41 (By similarity). Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1 (By similarity). Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (By similarity). Part of the BCR(ENC1) complex containing ENC1 (By similarity). Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP (By similarity). Part of a complex consisting of BRMS1, CUL3 and SPOP (By similarity). Component of the BCR(KLHL21) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL21 and RBX1 (By similarity). Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (By similarity). Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1 (PubMed:34491895). Part of a complex consisting of MACROH2A1, CUL3 and SPOP (By similarity). Component of the BCR(KLHL42) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL42 (By similarity). Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1 (By similarity). Interacts with KLHL42 (via the BTB domain) (By similarity). Interacts with KATNA1; the interaction is enhanced by KLHL42 (By similarity). Interacts with KCTD5, KLHL9, KLHL11, KLHL13, GAN, ZBTB16, KLHL3, KLHL15, KLHL20, KLHL36, GMCL2, BTBD1 (By similarity). Part of a complex that contains CUL3, RBX1 and GAN (By similarity). Interacts (via BTB domain) with KLHL17; the interaction regulates surface GRIK2 expression (By similarity). Interacts with KCTD7 (By similarity). Part of the BCR(GAN) complex containing GAN (By similarity). Part of the BCR(KEAP1) complex containing KEAP1 (PubMed:15282312, PubMed:16790436, PubMed:27697860). Interacts with KAT5 and ATF2 (By similarity). Interacts with KCTD17 in the BCR(KCTD17) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD17 and RBX1 (By similarity). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (By similarity). Interacts with COPS9 (By similarity). Interacts with PPP2R5B; this interaction is indirect and mediated through KLHL15-binding and leads to PPP2R5B proteasomal degradation (By similarity). Interacts with RBBP8/CtIP; this interaction is indirect and mediated through KLHL15-binding and leads to RBBP8 proteasomal degradation (By similarity). Interacts with KLHL24 in the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24 (By similarity). Interacts with RHOBTB2 (By similarity). Interacts with CYCE (PubMed:10500095). Interacts with KLHL10 (PubMed:16162871). Interacts with AURKA and KLHL18 (via BTB domain) (By similarity). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (By similarity). Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (By similarity). Component of the BCR(KBTBD2) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD2 and RBX1. Interacts with KBTBD2 (via the BTB domain) (PubMed:27708159).|||Golgi apparatus|||Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.|||Nucleus|||Null deficient mice are not viable. Extraembryonic ectoderm shows a greatly increased number of cells in S phase. In the trophectoderm cells are blocked to entry into S phase. Embryonic stem (ES) cells form tightly packed cell clusters with prominent actin cables and aberrant adhesions. ES cells are retained in proliferation, yet retain their pluripotency.|||Widely expressed, with highest expression in brain, spleen and testis. In the testis, it is mainly expressed in spermatids.|||centrosome|||flagellum|||spindle|||spindle pole http://togogenome.org/gene/10090:Rida ^@ http://purl.uniprot.org/uniprot/P52760 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Also promotes endoribonucleolytic cleavage of some transcripts by promoting recruitment of the ribonuclease P/MRP complex. Acts by bridging YTHDF2 and the ribonuclease P/MRP complex. RIDA/HRSP12 binds to N6-methyladenosine (m6A)-containing mRNAs containing a 5'-GGUUC-3' motif: cooperative binding of RIDA/HRSP12 and YTHDF2 to such transcripts lead to recruitment of the ribonuclease P/MRP complex and subsequent endoribonucleolytic cleavage.|||Belongs to the RutC family.|||Catalyzes the hydrolytic deamination of enamine/imine intermediates that form during the course of normal metabolism. May facilitate the release of ammonia from these potentially toxic reactive metabolites, reducing their impact on cellular components. It may act on enamine/imine intermediates formed by several types of pyridoxal-5'-phosphate-dependent dehydratases including L-threonine dehydratase.|||Cytoplasm|||Expressed predominantly in liver and kidney. Lower levels in lung and brain.|||Homotrimer. Interacts with YTHDF2.|||Mitochondrion|||Nucleus|||Peroxisome http://togogenome.org/gene/10090:Map1s ^@ http://purl.uniprot.org/uniprot/Q8C052 ^@ Developmental Stage|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAP1 family.|||Contaminating sequence. At the N-terminus.|||Expressed in embryo at 10 dpc onwards (at protein level).|||Expressed in ventral and dorsal horns of the spinal cord, hippocampus, cerebral cortex, molecular, Purkinje and granular cell layers of the cerebellum and in dorsal root ganglia of the PNS (at protein level). Expressed in brain, testis, heart, lung, kidney and liver.|||Heterodimer of a heavy and a light chain. Interacts with microtubules and actin. Both MAP1S heavy and light chains interact with microtubules. MAP1S light chain interacts with actin. Interacts with ESR1, LRPPRC, RASSF1, microtubules and VCY2. Interacts with WDR47 (via N-terminus of light chain) (By similarity). Interacts (via C-terminus) with GAN (via Kelch domains).|||Its C-terminal part of the heavy chain interacts with ESR1 (By similarity). The N-terminus of the heavy chain associates with the C-terminus of the light chain to form the heterodimer complex.|||Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis (By similarity). Involved in the formation of microtubule bundles.|||Nucleus|||cytoskeleton|||cytosol|||spindle http://togogenome.org/gene/10090:Mrfap1 ^@ http://purl.uniprot.org/uniprot/Q9CQL7 ^@ Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MORF4 family-associated protein family.|||Found in a complex composed of MORF4L1, MRFAP1 and RB1. Interacts via its N-terminus with MORF4L1. Interacts with CSTB and MORF4L2.|||Male mice are viable, fertile and show normal T-cell function.|||Nucleus|||Widely expressed in all tissues examined and as early as 7 days during embryonic development.|||perinuclear region http://togogenome.org/gene/10090:Abhd13 ^@ http://purl.uniprot.org/uniprot/Q80UX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the serine esterase family.|||Membrane http://togogenome.org/gene/10090:Lin54 ^@ http://purl.uniprot.org/uniprot/Q571G4 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the lin-54 family.|||Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, RBL2, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity).|||Component of the DREAM complex, a multiprotein complex that can both act as a transcription activator or repressor depending on the context. In G0 phase, the complex binds to more than 800 promoters and is required for repression of E2F target genes. In S phase, the complex selectively binds to the promoters of G2/M genes whose products are required for mitosis and participates in their cell cycle dependent activation. In the complex, acts as a DNA-binding protein that binds the promoter of CDK1 in a sequence-specific manner. Specifically recognizes the consensus motif 5'-TTYRAA-3' in target DNA.|||Contaminating sequence. Potential poly-A sequence.|||Nucleus|||The CRC domain mediates DNA-binding. It contains two CXC subdomains (joined by a flexible linker) which are both required for efficient association with target DNA. Each CXC subdomain coordinates three Zn(2+) ions. http://togogenome.org/gene/10090:Casq1 ^@ http://purl.uniprot.org/uniprot/O09165|||http://purl.uniprot.org/uniprot/Q6P3C3|||http://purl.uniprot.org/uniprot/Q8C7M8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calsequestrin family.|||Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.|||Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, often at the interface between subunits. Can bind around 80 Ca(2+) ions (By similarity). Regulates the release of lumenal Ca(2+) via the calcium release channel RYR1; this plays an important role in triggering muscle contraction. Negatively regulates store-operated Ca(2+) entry (SOCE) activity (By similarity).|||Detected in skeletal muscle (at protein level). Detected in skeletal muscle.|||Endoplasmic reticulum|||Mice are viable and fertile, but have a lower body weight than wild-type, due to a reduction in fast-twitch muscle mass. Fast-twitch muscle from mutant mice exhibits slower contraction kinetics and requires more time to achieve peak tension and to achieve half-relaxation after a contraction. Fast-twitch muscle fibers from mutant mice show a strikingly altered structure of the calcium release units in the sarcoplasmic reticulum with a strongly increased number of ryanodine receptors, plus narrower sarcoplasmic reticulum cisternae. In addition, the number of mitochondria is increased in mutant muscle. Mutant muscle fibers show smaller calcium transients upon electrical stimulation and release less Ca(2+) in response to caffeine.|||Mitochondrion matrix|||Monomer; increases in response to a depletion of intracellular calcium. Homodimer. Homotetramer and homopolymer. Can form linear homooligomers. Ca(2+) ions promote oligomerization. Interacts (via C-terminal end and preferentially with the monomeric form) with STIM1; this interaction increases in response to a depletion of intracellular calcium, decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) entry (SOCE) activity. Interacts with ASPH and TRDN.|||N-glycosylated.|||Sarcoplasmic reticulum|||Sarcoplasmic reticulum lumen|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Csta2 ^@ http://purl.uniprot.org/uniprot/Q9D8D6 ^@ Similarity ^@ Belongs to the cystatin family. http://togogenome.org/gene/10090:Pnrc1 ^@ http://purl.uniprot.org/uniprot/Q3TWH3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Cwh43 ^@ http://purl.uniprot.org/uniprot/Q91YL7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PGAP2IP family.|||Interacts with PGAP2/FRAG1.|||Involved in lipid remodeling during GPI-anchor maturation.|||Membrane http://togogenome.org/gene/10090:Brd4 ^@ http://purl.uniprot.org/uniprot/Q9ESU6 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds acetylated histone H4. Interacts with p53/TP53; the interaction is direct (By similarity). Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex (PubMed:16109376). Interacts with RELA (when acetylated at 'Lys-310'). Interacts (via NET domain) with NSD3, CHD4, BICRA and ATAD5. The interaction with BICRA bridges BRD4 to the GBAF complex. Interacts (via NET domain) with JMJD6 (via JmjC and N-terminal domains); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers. Interacts with NSD3 (By similarity).|||Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure (PubMed:10938129). During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II (By similarity). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:16109376). According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo. In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B. Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (By similarity).|||Chromosome|||Embryonic lethal. Embryos ndie shortly after implantation and are compromised in their ability to maintain an inner cell mass.|||Nucleus|||Phosphorylation by CK2 disrupt the intramolecular binding between the bromo domain 2 and the NPS region and promotes binding between the NPS and the BID regions, leading to activate the protein and promote binding to acetylated histones. In absence of phosphorylation, BRD4 does not localize to p53/TP53 target gene promoters, phosphorylation promoting recruitment to p53/TP53 target promoters.|||Some specific inhibitors of Brd4 that prevent binding to acetylated histones by binding Asn-140 and Asn-434 are promising therapeutic molecules for the treatment of leukemias. JQ1, a thieno-triazolo-1,4-diazepine derivative, and I-BET, a benzodiazepine derivative, have been tested on tumors with success. Treatment with GSK1210151A (I-BET151, a I-BET derivative) has strong effets on mixed lineage leukemia and promotes myeloid differentiation and leukemia stem-cell depletion (PubMed:21814200, PubMed:21964340).|||The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-434, respectively (PubMed:19828451). The exact combination of modified histone tails required to recruit BRD4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3. A number of specific inhibitors bind competitively to acetyl-lysine-binding residues Asn-140 and Asn-434, promoting removal from acetylated histones. Many of these inhibitors are benzodiazepine derivatives.|||The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex. It is also required for maintenance of higher-order chromatin structure.|||The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (NSD3, JMJD6, CHD4, GLTSCR1 and ATAD5). http://togogenome.org/gene/10090:Ccr5 ^@ http://purl.uniprot.org/uniprot/P51682 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with PRAF2. Efficient ligand binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4. Interacts with GRK2. Interacts with ARRB1 and ARRB2. Interacts with CNIH4. Interacts with S100A4; this interaction stimulates T-lymphocyte chemotaxis.|||O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site. Also sialylated glycans present which contribute to chemokine binding (By similarity).|||Palmitoylation in the C-terminal is important for cell surface expression.|||Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES.|||Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor.|||Sulfated on at least 2 of the N-terminal tyrosines. Sulfation is required for efficient binding of the chemokines, CCL3 and CCL4 (By similarity). http://togogenome.org/gene/10090:Naa25 ^@ http://purl.uniprot.org/uniprot/B2RQV1|||http://purl.uniprot.org/uniprot/Q8BWZ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MDM20/NAA25 family.|||Component of the N-terminal acetyltransferase B (NatB) complex which is composed of NAA20 and NAA25.|||Cytoplasm|||Non-catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. May play a role in normal cell-cycle progression. http://togogenome.org/gene/10090:Or5p55 ^@ http://purl.uniprot.org/uniprot/Q8VGI4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Zfp26 ^@ http://purl.uniprot.org/uniprot/P10076 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Chst4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1C9|||http://purl.uniprot.org/uniprot/Q9R1I1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.|||Golgi apparatus membrane|||Membrane|||Mice are impaired in lymphocyte homing and exhibit faster lymphocyte rolling and reduced lymphocyte sticking in HEV. The epitope of SELL ligands recognized by the MECA-79 antibody is greatly reduced or abolished in the abluminal aspect of HEV. Simultaneous knockdown of CHST4 and CHST2 results in lower contact hypersensitivity response when compared to wild-type littermates.|||Monomer.|||Specifically expressed in high endothelial venules (HEV) of peripheral lymph nodes.|||Sulfotransferase involved in SELL/L-selectin ligand biosynthesis pathway. Catalyzes the transfer of the sulfate group from 3'-phospho-5'-adenylyl sulfate (PAPS) onto the hydroxyl group at C-6 position of the non-reducing N-acetylglucosamine (GlcNAc) residue within O-linked mucin-type glycans (PubMed:10435581, PubMed:16227985, PubMed:15319280, PubMed:16227986, PubMed:14597732, PubMed:15111310). Contributes to generate sialyl 6-sulfo Lewis X determinant (also known as MECA-79 epitope) for SELL recognition, a prerequisite for continuous lymphocyte homing into peripheral lymph nodes and antigen immune surveillance. Transfers the sulfate group primarily on core 2 GlcNAcbeta1-6(Galbeta1-3)GalNAcalphaSer/Thr and extended core 1 GlcNAcbeta1-3Galbeta1-3GalNAcalphaSer/Thr based O-linked glycans on CD34 and GLYCAM1 peripheral node addressins (PNAds) expressed on the lumenal side of high endothelial venules (HEVs) (PubMed:10435581, PubMed:16227985, PubMed:15319280, PubMed:16227986, PubMed:15111310, PubMed:14593101). The recognition of PNAds by SELL initiates a multistep process comprising tethering and rolling of blood lymphocytes on HEVs against the blood flow, followed by chemokine signaling, integrin-mediated lymphocyte adhesion onto endothelial cells and lymphocyte transendothelial migration. Modulates rolling velocity and differential T and B lymphocyte recruitment into peripheral lymph nodes, with a major role in B lymphocyte homing (PubMed:16227985, PubMed:15319280, PubMed:16227986, PubMed:14597732, PubMed:10435581). Might be redundant in sulfation of MADCAM1 and lymphocyte trafficking to mesenteric lymph nodes (PubMed:10435581, PubMed:11520459, PubMed:16227986). Can also sulfonate core 3 GlcNAcbeta1-3GalNAc-R based glycans as well as GlcNAcbeta1-3Galbeta1-Glc, GlcNAcbeta1-6ManOMe and GlcNAcbeta1-2Man oligosaccharides, which might be ectopically expressed during tumorigenesis (By similarity). http://togogenome.org/gene/10090:Mgst2 ^@ http://purl.uniprot.org/uniprot/A0A0A6YWX7|||http://purl.uniprot.org/uniprot/A2RST1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Catalyzes several different glutathione-dependent reactions. Catalyzes the glutathione-dependent reduction of lipid hydroperoxides, such as 5-HPETE. Has glutathione transferase activity, toward xenobiotic electrophiles, such as 1-chloro-2, 4-dinitrobenzene (CDNB). Catalyzes also the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4 (LTC4) (By similarity). Involved in oxidative DNA damage induced by ER stress and anticancer agents by activating LTC4 biosynthetic machinery in nonimmune cells (PubMed:26656251).|||Deficient mice display resistance to induced ER stress with reduced cell death and mortality.|||Each monomer binds on GSH molecule but only one subunit is catalytically active.|||Endoplasmic reticulum membrane|||Homotrimer.|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Kdelr3 ^@ http://purl.uniprot.org/uniprot/Q8R1L4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ERD2 family.|||Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).|||COPI-coated vesicle membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum. http://togogenome.org/gene/10090:Ska3 ^@ http://purl.uniprot.org/uniprot/Q8C263 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SKA3 family.|||Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. In the complex, it mediates the microtubule-stimulated oligomerization. Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules.|||Component of the SKA1 complex, composed of SKA1, SKA2 and SKA3. The core SKA1 complex is composed of 2 SKA1-SKA2 heterodimers, each heterodimer interacting with a molecule of the SKA3 homodimer. The core SKA1 complex associates with microtubules and forms oligomeric assemblies. Interacts with SKA1; the interaction is direct.|||kinetochore|||spindle http://togogenome.org/gene/10090:Gm21627 ^@ http://purl.uniprot.org/uniprot/A0A087WRK1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Dnajc30 ^@ http://purl.uniprot.org/uniprot/P59041 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the ATP synthase complex. Interacts with MT-ATP6; interaction is direct. Interacts with ATP5MC2; interaction is direct.|||In brain, expressed in gray matter structures.|||Mice are smaller and have a decreased weight (PubMed:30318146). Neocortical projection neurons display morphological defects reminiscent of Williams-Beuren syndrome (WBS) in human, characterized by less complex dendritic architecture and a smaller corpus callosum (PubMed:30318146). Mitochondria show decreased ATP production (PubMed:30318146). Mice do not show significant systemic metabolic defects (PubMed:30318146).|||Mitochondrial protein enriched in neurons that acts as a regulator of mitochondrial respiration (PubMed:30318146). Associates with the ATP synthase complex and facilitates ATP synthesis (PubMed:30318146). May be a chaperone protein involved in the turnover of the subunits of mitochondrial complex I N-module. It facilitates the degradation of N-module subunits damaged by oxidative stress, and contributes to complex I functional efficiency (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pramel34 ^@ http://purl.uniprot.org/uniprot/E0CZF1 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Ndufa8 ^@ http://purl.uniprot.org/uniprot/Q9DCJ5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA8 subunit family.|||Complex I is composed of 45 different subunits.|||Contains four C-X9-C motifs that are predicted to form a helix-coil-helix structure, permitting the formation of intramolecular disulfide bonds.|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Csad ^@ http://purl.uniprot.org/uniprot/Q9DBE0 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Activated by Mn(2+). Inhibited by bis-carboxymethyl-trithiocarbonate, ethylxanthogenacetic acid and 2,5-disulfoaniline. Not affected by Li(+) within 0.05-40 mM concentration range.|||Belongs to the group II decarboxylase family.|||Catalyzes the decarboxylation of L-aspartate, 3-sulfino-L-alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine, hypotaurine and taurine, respectively. The preferred substrate is 3-sulfino-L-alanine. Does not exhibit any decarboxylation activity toward glutamate.|||Expressed in kidney and liver not detected in lymphoid tissues and lung. Expressed in kidney, liver and brain. 7 and 4 times higher expression in kidney and liver than in brain, respectively. Low level of detection in skeletal muscle. Expressed in brain, olfactory bulb, liver, skeletal muscle and kidney with the highest expression in liver and lowest in skeletal muscle (at protein level) (PubMed:26327310).|||Expression in the brain decreases with age as detected from 17 dpc to 12 months.|||Homodimer. http://togogenome.org/gene/10090:Plppr5 ^@ http://purl.uniprot.org/uniprot/Q8BJ52 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Cell membrane|||Has most probably no lipid phosphatase activity (By similarity). Critical residues that support the reaction mechanism in active members of that protein family, including the residues of the active site acting respectively as proton donor and nucleophile, are not conserved.|||Induces filopodia formation and promotes neurite growth in a CDC42-independent manner; impedes neurite growth inhibitory-mediated axonal retraction. http://togogenome.org/gene/10090:Zfp280c ^@ http://purl.uniprot.org/uniprot/Q6P3Y5 ^@ Function|||Subcellular Location Annotation ^@ May function as a transcription factor.|||Nucleus http://togogenome.org/gene/10090:Wfs1 ^@ http://purl.uniprot.org/uniprot/P56695 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Highly expressed in the developing lens.|||Interacts with ATP6V1A.|||Participates in the regulation of cellular Ca(2+) homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca(2+) store (By similarity). Negatively regulates the ER stress response and positively regulates the stability of V-ATPase subunits ATP6V1A and ATP1B1 by preventing their degradation through an unknown proteasome-independent mechanism (By similarity).|||secretory vesicle http://togogenome.org/gene/10090:Epor ^@ http://purl.uniprot.org/uniprot/P14753|||http://purl.uniprot.org/uniprot/Q3UTV9 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 1 subfamily.|||Cell membrane|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Expressed in relatively mature erythroid progenitor cells and in EPO-responsive erythroleukemia cells.|||Forms homodimers on EPO stimulation.|||Forms homodimers on EPO stimulation. The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN, the adapter protein APS, PTPN6, PTPN11, JAK2, PI3 kinases, STAT5A/B, SOCS3 and CRKL. The N-terminal SH2 domain of PTPN6 binds Tyr-453 and inhibits signaling through dephosphorylation of JAK2. APS binding also inhibits the JAK-STAT signaling. Binding to PTPN11, preferentially through the N-terminal SH2 domain, promotes mitogenesis and phosphorylation of PTPN11. Binding of JAK2 (through its N-terminal) promotes cell-surface expression. Interaction with the ubiquitin ligase NOSIP mediates EPO-induced cell proliferation. Interacts with ATXN2L (By similarity). Forms heterooligomers with friend spleen focus-forming virus (FSFFV) gp55, probably via their respective transmembrane domains. Interacts with INPP5D/SHIP1.|||Interaction with FSFFV envelope-like membrane glycoprotein gp55 leads to ligand-independent activation of EPOR and to the abnormally rapid proliferation of erythroid precursor cells.|||Membrane|||On EPO stimulation, phosphorylated on C-terminal tyrosine residues by JAK2. The phosphotyrosine motifs are also recruitment sites for several SH2-containing proteins and adapter proteins which mediate cell proliferation. Phosphorylation on Tyr-453 is required for PTPN6 interaction, Tyr-425 for PTPN11. Tyr-425 is also required for SOCS3 binding, but Tyr-453/Tyr-455 motif is the preferred binding site (By similarity).|||Receptor for erythropoietin.|||Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase.|||Secreted|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||The identity of the C-linked hexose on the WXXW motif has not been determined. It is probably mannose.|||Ubiquitinated by NOSIP; appears to be either multi-monoubiquitinated or polyubiquitinated. Ubiquitination mediates proliferation and survival of EPO-dependent cells (By similarity). Ubiquitination at Lys-280 mediates receptor internalization, whereas ubiquitination at Lys-452 promotes trafficking of activated receptors to the lysosomes for degradation.|||Viral promoter integration by Friend spleen focus-forming virus (F-SFFVP) in the murine erythroleukemia cell line F5-5, results in aberrant EPOR sequences and EPOR overexpression in erythroid progenitor cells. http://togogenome.org/gene/10090:Gchfr ^@ http://purl.uniprot.org/uniprot/P99025|||http://purl.uniprot.org/uniprot/Q4VAF4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GFRP family.|||Homopentamer. Forms a complex with GCH1 where a GCH1 homodecamer is sandwiched by two GFRP homopentamers. Interacts with GCH1 (By similarity).|||Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1. This inhibition is reversed by L-phenylalanine (By similarity).|||Membrane|||Nucleus|||Nucleus membrane|||cytosol http://togogenome.org/gene/10090:Mrpl41 ^@ http://purl.uniprot.org/uniprot/Q9CQN7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL41 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Interacts with BCL2.|||Component of the mitochondrial ribosome large subunit. Also involved in apoptosis and cell cycle. Enhances p53/TP53 stability, thereby contributing to p53/TP53-induced apoptosis in response to growth-inhibitory condition. Enhances p53/TP53 translocation to the mitochondria. Has the ability to arrest the cell cycle at the G1 phase, possibly by stabilizing the CDKN1A and CDKN1B (p27Kip1) proteins.|||Mitochondrion http://togogenome.org/gene/10090:Epsti1 ^@ http://purl.uniprot.org/uniprot/Q8VDI1 ^@ Disruption Phenotype|||Function|||Induction|||Tissue Specificity ^@ Down-regulation of M1 macrophage marker genes, including Il12a, Il12b, Cxcl9, Cxcl10, Cxcl11, Hif1a and Il23a, and up-regulation of M2 marker genes, including Arg1, Ym1, Msr1 and Ccl17, in M1 macrophages. In bone marrow derived macrophages, impaired induction of M1 macrophage marker gene expression and impaired phosphorylation and nuclear localization of Rela/p65 and Stat1 after LPS and IFNG stimulation and enhanced M2 macrophage marker gene expression after Il4 stimulation. Reduced number of MHC class II- and F4/80-expressing cells within the population of M1 marker-expressing macrophages.|||Expressed in the spleen, with expression in T cells, B cells, natural killer cells and natural killer T cells and high expression in monocytes and macrophages.|||Plays a role in M1 macrophage polarization and is required for the proper regulation of gene expression during M1 versus M2 macrophage differentiation (PubMed:29217193). Might play a role in RELA/p65 and STAT1 phosphorylation and nuclear localization upon activation of macrophages (PubMed:29217193).|||Up-regulated in macrophages upon induction by lipopolysaccharides (LPS) and IFNG. http://togogenome.org/gene/10090:Rab6b ^@ http://purl.uniprot.org/uniprot/P61294 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasmic vesicle|||Endoplasmic reticulum-Golgi intermediate compartment|||Golgi apparatus membrane|||Interacts (GTP-bound) with BICD1 (via C-terminus); the interaction is direct. Interacts (GDP-bound) with DYNLRB1. Interacts (GTP-bound) with APBA1/MINT1 isoform 3, also called Mint1_826. Interacts (GTP-bound) with VPS13B.|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology. Recruits VPS13B to the Golgi membrane. Regulates the compacted morphology of the Golgi. Seems to have a role in retrograde membrane traffic at the level of the Golgi complex. May function in retrograde transport in neuronal cells. Plays a role in neuron projection development. http://togogenome.org/gene/10090:Luc7l2 ^@ http://purl.uniprot.org/uniprot/E9Q715|||http://purl.uniprot.org/uniprot/Q05CX5|||http://purl.uniprot.org/uniprot/Q3U5L2|||http://purl.uniprot.org/uniprot/Q3UGK2|||http://purl.uniprot.org/uniprot/Q3USM3|||http://purl.uniprot.org/uniprot/Q3UZ17|||http://purl.uniprot.org/uniprot/Q7TNC4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All isoforms are expressed in brain, kidney, heart, thymus, stomach, skeletal muscle, testis and spinal cord.|||Belongs to the Luc7 family.|||Interacts with SCNM1.|||May bind to RNA via its Arg/Ser-rich domain.|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Ppp3cc ^@ http://purl.uniprot.org/uniprot/A0A2I3BPC5|||http://purl.uniprot.org/uniprot/P48455|||http://purl.uniprot.org/uniprot/Q80XK0 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)-bound calmodulin following an increase in intracellular Ca(2+). At low Ca(2+) concentrations, the catalytic subunit (also known as calcineurin A) is inactive and is bound to the regulatory subunit (also known as calcineurin B) in which only two high-affinity binding sites are occupied by Ca(2+). In response to elevated calcium levels, the occupancy of the low-affinity sites on calcineurin B by Ca(2+) causes a conformational change of the C-terminal regulatory domain of calcineurin A, resulting in the exposure of the calmodulin-binding domain and in the partial activation of calcineurin A. The subsequent binding of Ca(2+)-bound calmodulin leads to the displacement of the autoinhibitory domain from the active site and possibly of the autoinhibitory segment from the substrate binding site which fully activates calcineurin A.|||Belongs to the PPP phosphatase family. PP-2B subfamily.|||Binds 1 Fe(3+) ion per subunit.|||Binds 1 zinc ion per subunit.|||Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32.|||Expressed in osteoblasts and bone marrow (at protein level) (PubMed:16286645). Expressed in the testis (PubMed:1309945, PubMed:34446558). Expressed in the sperm midpiece in a SPATA33-dependent manner (at protein level) (PubMed:34446558).|||Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). In response to an increase in Ca(2+) intracellular levels, forms a complex composed of PPP3CC/calcineurin A, calcineurin B and calmodulin. Interacts (via calmodulin-binding domain) with calmodulin; the interaction depends on calmodulin binding to Ca(2+) (By similarity). Interacts with UNC119 (PubMed:31696965). Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558). Interacts with VDAC2 in a SPATA33-dependent manner (PubMed:34446558).|||Mitochondrion|||Possible isomerization of Pro-305 within the SAPNY motif triggers a conformation switch which affects the organization and thus accessibility of the active site and the substrate binding region (PxIxIF motif). The trans- to cis-transition may favor calcineurin A activation and substrate binding. The reverse cis- to trans-transition may be enhanced by peptidyl-prolyl isomerases such as PPIA.|||The autoinhibitory domain prevents access to the catalytic site.|||The autoinhibitory segment prevents access to the substrate binding site. http://togogenome.org/gene/10090:Actl7b ^@ http://purl.uniprot.org/uniprot/Q9QY83 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the actin family.|||Testis specific.|||cytoskeleton http://togogenome.org/gene/10090:Cfap90 ^@ http://purl.uniprot.org/uniprot/Q9DAR0 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in sperm (at protein level).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||On the 2D-gel the determined pI of this protein is: 7.7, its MW is: 22 kDa.|||cilium axoneme http://togogenome.org/gene/10090:Edil3 ^@ http://purl.uniprot.org/uniprot/O35474|||http://purl.uniprot.org/uniprot/Q8C4U8|||http://purl.uniprot.org/uniprot/Q8C8K0 ^@ Caution|||Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ EGF2 and EGF3 form a rigid rod via an interdomain calcium ion binding site, while the long linker between EGF1 and EGF2 lends considerable flexibility to EGF1.|||Expressed in angioblasts and early endothelial cells. By embryonic day 13.5, also expressed in a restricted group of non-endothelial cells including chondrocytes and retinal neurons.|||Expressed in the embryo from day 7. After day 15.5, expression decreases and disappears completely by the time of birth.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Promotes adhesion of endothelial cells through interaction with the alpha-v/beta-3 integrin receptor. Inhibits formation of vascular-like structures. May be involved in regulation of vascular morphogenesis of remodeling in embryonic development.|||Secreted http://togogenome.org/gene/10090:Sh2d1b2 ^@ http://purl.uniprot.org/uniprot/Q45HK4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family. In SLAM signaling may cooperate with Sh2d1a/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through Cd244/2b4. However, conflicting results are reported which may reflect the use of different strain backgrounds. Proposed to act as an inhibitor of Cd244-mediated NK cell function including cytotoxicity and IFN-gamma production, the latter found also by triggering Klra4 and Klrk1 next to Cd244 (PubMed:16127454). Seems to positively regulate Cd244- and Cd84-dependent NK cell functions implicating Cd244-mediated phosphorylation of Vav1 (PubMed:20962259).|||Expressed in spleen. Expressed in macrophages, CD8(+) T-Cells and NK cells (PubMed:16425036). Conflictingly found only in NK cells (PubMed:16127454).|||Interacts with SLAMF1 (phosphorylated). Interacts with CD244. Interacts with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains). http://togogenome.org/gene/10090:Lrpprc ^@ http://purl.uniprot.org/uniprot/Q6PB66 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed at embryonic stages 7 dpc, 11 dpc, 15 dpc and 17 dpc with a slight increase of levels during development.|||Interacts with CECR2, HEBP2, MAP1S and UXT (By similarity). Interacts with PPARGC1A (By similarity). Interacts with FOXO1. Component of mRNP complexes associated with HNRPA1 (By similarity). Interacts (via N-terminus) with EIF4E; the interaction promotes association of EIF4E with 4ESE-containing mRNAs (PubMed:19262567, PubMed:28325843). Interacts with exportin XPO1/CRM1; interacts both alone and in complex with EIF4E and 4ESE-containing mRNAs to form an EIF4E-dependent mRNA export complex (By similarity). Interacts with importin IPO8; the interaction occurs when LRPPRC is in its RNA-free form and returns LRPPRC to the nucleus for further export rounds (By similarity).|||May play a role in RNA metabolism in both nuclei and mitochondria. In the nucleus binds to HNRPA1-associated poly(A) mRNAs and is part of nmRNP complexes at late stages of mRNA maturation which are possibly associated with nuclear mRNA export. Positively modulates nuclear export of mRNAs containing the EIF4E sensitivity element (4ESE) by binding simultaneously to both EIF4E and the 4ESE and acting as a platform for assembly for the RNA export complex (By similarity). Also binds to exportin XPO1/CRM1 to engage the nuclear pore and traffic the bound mRNAs to the cytoplasm (By similarity). May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. Plays a role in translation or stability of mitochondrially encoded cytochrome c oxidase (COX) subunits. May be involved in transcription regulation. Cooperates with PPARGC1A to regulate certain mitochondrially encoded genes and gluconeogenic genes and may regulate docking of PPARGC1A to transcription factors. Seems to be involved in the transcription regulation of the multidrug-related genes MDR1 and MVP. Part of a nuclear factor that binds to the invMED1 element of MDR1 and MVP gene promoters (By similarity). Binds single-stranded DNA.|||Mitochondrion|||Nucleus|||Nucleus inner membrane|||Nucleus outer membrane|||Strongly expressed in heart, liver and kidney. Weakly expressed in brain, skeletal muscle and testes.|||nucleoplasm http://togogenome.org/gene/10090:Uba3 ^@ http://purl.uniprot.org/uniprot/Q3TL72|||http://purl.uniprot.org/uniprot/Q66JT6|||http://purl.uniprot.org/uniprot/Q8C878 ^@ Activity Regulation|||Disease Annotation|||Function|||Miscellaneous|||Similarity|||Subunit ^@ Arg-211 acts as a selectivity gate, preventing misactivation of ubiquitin by this NEDD8-specific E1 complex.|||Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.|||Binding of TP53BP2 to the regulatory subunit NAE1 decreases activity.|||Catalytic subunit of the dimeric E1 enzyme, which activates NEDD8.|||Catalytic subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Down-regulates steroid receptor activity. Necessary for cell cycle progression.|||Defects in Uba3 are a cause of embryonic lethality. Mouse embryos deficient in Uba3 die at the preimplantation stage (PubMed:11696557).|||Heterodimer of UBA3 and NAE1. Interacts with NEDD8, UBE2F and UBE2M. Binds ESR1 and ESR2 with bound steroid ligand (By similarity). Interacts with TBATA. http://togogenome.org/gene/10090:Cd86 ^@ http://purl.uniprot.org/uniprot/P42082 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed on activated B-cells.|||Homodimer. Interacts with MARCH8 (By similarity). Interacts (via cytoplasmic domain) with PHB1 and PHB2; the interactions increases after priming with CD40 (PubMed:23241883).|||Polyubiquitinated; which is promoted by MARCH8 and results in endocytosis and lysosomal degradation.|||Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Also involved in the regulation of B cells function, plays a role in regulating the level of IgG(1) produced. Upon CD40 engagement, activates NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (PubMed:23241883). http://togogenome.org/gene/10090:Chst5 ^@ http://purl.uniprot.org/uniprot/Q9QUP4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.|||Expressed in cornea.|||Golgi apparatus membrane|||In human, there are 2 related proteins, CHST5 and CHST6, the latter mediating sulfation of keratan in cornea. In mouse however, there is no CHST6 protein, CHST5 functioning as a corneal keratan sulfotransferase and mediates such function.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues of keratan. Mediates sulfation of keratan in cornea. Keratan sulfate plays a central role in maintaining corneal transparency. Acts on the non-reducing terminal GlcNAc of short and long carbohydrate substrates that have poly-N-acetyllactosamine structures. May also have activity toward O-linked sugars of mucin-type acceptors. http://togogenome.org/gene/10090:Or2y3 ^@ http://purl.uniprot.org/uniprot/Q8VGC8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gabra1 ^@ http://purl.uniprot.org/uniprot/P62812|||http://purl.uniprot.org/uniprot/Q3URD4|||http://purl.uniprot.org/uniprot/Q544F7 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by benzodiazepines, the neuroanesthetic alphaxalone and pentobarbital (By similarity). Inhibited by the antagonist bicuculline (By similarity).|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA1 sub-subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||Gene knockdown in orbitofrontal prefrontal cortex results in an inability of mice to select actions based on their consequences, developing instead habit-like behavioral inflexibility.|||Glycosylated.|||Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (By similarity). Interacts with UBQLN1 (By similarity). Interacts with TRAK1 (PubMed:16380713). Interacts with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (By similarity). Interacts with NLGN2 (By similarity). Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (PubMed:31601770).|||Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:27129275). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:27129275). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (PubMed:27129275). The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (PubMed:27129275). GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane|||The extracellular domain contributes to synaptic contact formation. http://togogenome.org/gene/10090:Aspdh ^@ http://purl.uniprot.org/uniprot/Q9DCQ2 ^@ Similarity ^@ Belongs to the L-aspartate dehydrogenase family. http://togogenome.org/gene/10090:Tmem160 ^@ http://purl.uniprot.org/uniprot/Q9D938 ^@ Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM160 family.|||Expressed in peripheral sensory neurons of dorsal root ganglia (DRG).|||Homozygous knockout mice for Tmem160 are healthy and fertile and display normal motor function regarding coordination and locomotion as well as similar somatosensory thresholds for mechanical (tactile) and heat stimulation as wild-type littermates (PubMed:34936870). Homozygous knockout male mice show a delay establishment of tactile hypersensitivity and alterations in selfgrooming after nerve injury (PubMed:34936870). Conditional knockout mice lacking Tmem160 in sensory neurons of dorsal root ganglia (DRG) are healthy and fertile (PubMed:34936870).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Tnmd ^@ http://purl.uniprot.org/uniprot/Q9EP64 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the chondromodulin-1 family.|||Expression already detected at 9.5 dpc and maintained throughout embryonic development. At 17.5 dpc, high levels found in tendons and ligaments of the skeletomuscular system, including the knee joint, the upper limb and the intercostal ligaments. At this developmental stage, high expression is also detected in the tendinous part of the diaphragm. By contrast, low levels are observed in resting and proliferative chondrocytes of long bones and vertebral bodies, and in the cartilaginous part of the intervertebral disks. No expression in hypertrophic chondrocytes. Outside the skeletomuscular system, expressed in neuronal cells of all brain regions and the spinal cord, liver, lung, bowels, thymus and eye.|||May be an angiogenesis inhibitor.|||Membrane|||Nucleus envelope|||Widely expressed with highest expression in tendons and ligaments, in the diaphragm, eye and skeletal muscle. Expressed in neuronal cells of all brain regions. Very low expression, if any, in glial cells. http://togogenome.org/gene/10090:Rpl4 ^@ http://purl.uniprot.org/uniprot/Q564E8|||http://purl.uniprot.org/uniprot/Q9D8E6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL4 family.|||Citrullinated by PADI4.|||Component of the large ribosomal subunit (PubMed:36517592). May bind IPO9 with low affinity (By similarity). Interacts with RBM3 (By similarity).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm http://togogenome.org/gene/10090:Slc22a16 ^@ http://purl.uniprot.org/uniprot/Q497L8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Facilitative organic cation transporter that mediates the transport of carnitine as well as the polyamine spermidine. Mediates the partially Na(+)-dependent bidirectional transport of carnitine. May mediate L-carnitine secretion from testis epididymal epithelium into the lumen which is involved in the maturation of spermatozoa. http://togogenome.org/gene/10090:Ero1b ^@ http://purl.uniprot.org/uniprot/Q8R2E9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EROs family.|||Endoplasmic reticulum membrane|||Glutathione may be required to regulate its activity in the endoplasmic reticulum.|||Homodimer; disulfide-linked (By similarity). Heterodimer with ERO1A; disulfide-linked (By similarity). Also detected as monomer. Homodimers may be somewhat less active than monomers. The abundance of monomers and homodimers may be tissue-specific. Interacts with P4HB (By similarity). Interacts with ERP44 (By similarity).|||N-glycosylated.|||Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Other protein disulfide isomerase family members can also be reoxidized, but at lower rates compared to P4HB, including PDIA2, PDIA3, PDIA4, PDIA6 and NXNDC12. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell (By similarity). Involved in oxidative proinsulin folding in pancreatic cells, hence required for glucose homeostasis in vivo.|||Predominantly expressed in stomach and pancreas (mostly in the islets of Langerhans) (at protein level).|||The Cys-90/Cys-95 and Cys-393/Cys-396 disulfide bonds constitute the redox-active center. The Cys-90/Cys-95 disulfide bond may accept electron from P4HB and funnel them to the active site disulfide Cys-393/Cys-396 (By similarity). http://togogenome.org/gene/10090:Vmn1r237 ^@ http://purl.uniprot.org/uniprot/Q8R296 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ms4a4c ^@ http://purl.uniprot.org/uniprot/Q9D3F6 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Crip3 ^@ http://purl.uniprot.org/uniprot/Q6Q6R3 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed specifically by the thymus. http://togogenome.org/gene/10090:Amn1 ^@ http://purl.uniprot.org/uniprot/B8JKV0 ^@ Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the AMN1 family.|||Expressed in the Sertoli cells of the testis.|||Interacts with TASOR. http://togogenome.org/gene/10090:Ube2l6 ^@ http://purl.uniprot.org/uniprot/Q9QZU9 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3.|||ISGylated.|||Interacts with RNF19A, RNF19B and RNF144B. Interacts with FLT3 (tyrosine phosphorylated). http://togogenome.org/gene/10090:Vip ^@ http://purl.uniprot.org/uniprot/A0A0R4J003|||http://purl.uniprot.org/uniprot/P32648 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glucagon family.|||PHM-27 is a potent agonist of the calcitonin receptor CALCR, with similar efficacy as calcitonin (By similarity). PHM also causes vasodilation.|||Secreted|||VIP causes vasodilation, lowers arterial blood pressure, stimulates myocardial contractility, increases glycogenolysis and relaxes the smooth muscle of trachea, stomach and gall bladder. http://togogenome.org/gene/10090:Itgb2l ^@ http://purl.uniprot.org/uniprot/D3YXH8|||http://purl.uniprot.org/uniprot/Q3UV74 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin beta chain family.|||Cell membrane|||During inflammatory stimulation, plays a role in retaining Cxcl13-expressing cells at the site of the inflammatory response.|||Expressed predominantly in maturing and mature neutrophils.|||Membrane|||Mice display normal neutrophil maturation and function including appropriate migration into sites of inflammation and response to bacterial infection. Following inflammatory stimulus in the peritoneal cavity, they display decreased levels of Cxcl13 due to the migration of resident Cxcl13-expressing macrophages from the peritoneal cavity during the inflammatory response.|||Monomer and homodimer (Probable). Unlike integrin beta chains, no alpha chain partner has yet been found.|||N-glycosylated.|||Strain C57BL/6 preferentially expresses isoform 1 while strains BALB/c and C3H/HeJ preferentially express isoform 2. This is due to a single nucleotide difference at the second splice acceptor site in exon 13 which results in production of isoform 2 when this splice site is used in strains BALB/c and C3H/HeJ.|||The human orthologous protein seems not to exist. http://togogenome.org/gene/10090:Scgb1b19 ^@ http://purl.uniprot.org/uniprot/F6WYW0 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Hus1b ^@ http://purl.uniprot.org/uniprot/Q059L7|||http://purl.uniprot.org/uniprot/Q8K572 ^@ Similarity|||Subunit ^@ Belongs to the HUS1 family.|||Interacts with RAD1 and RAD9B. http://togogenome.org/gene/10090:Slc52a3 ^@ http://purl.uniprot.org/uniprot/Q9D6X5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the riboflavin transporter family.|||Cell membrane|||Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism.|||Within the small intestine, it is particulary expressed in the jujenum and the ileum. Almost negligible expression in the stomach, duodenum, and large intestine. http://togogenome.org/gene/10090:Vmn1r22 ^@ http://purl.uniprot.org/uniprot/Q8R2D1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hspb7 ^@ http://purl.uniprot.org/uniprot/P35385 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small heat shock protein (HSP20) family.|||Cajal body|||Cytoplasm|||Found in both cardiac and slow skeletal (soleus) muscle.|||Interacts with C-terminal domain of actin-binding protein 280.|||Nucleus http://togogenome.org/gene/10090:Hexim2 ^@ http://purl.uniprot.org/uniprot/Q3TVI4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HEXIM family.|||Homooligomer and heterooligomer with HEXIM1; probably dimeric. Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1). Interacts with CCNT2.|||Nucleus|||The coiled-coil domain mediates oligomerization.|||Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor. Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation. http://togogenome.org/gene/10090:Ap4m1 ^@ http://purl.uniprot.org/uniprot/Q9JKC7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). Interacts with tyrosine-based sorting signals on the cytoplasmic tail of cargo proteins such as APP, ATG9A, LAMP2 and NAGPA. Interacts with the C-terminal domain of GRID2 (By similarity). Interacts with GRIA1 and GRIA2; the interaction is indirect via CACNG3 (PubMed:18341993). Interacts with CACNG3; CACNG3 associates GRIA1 and GRIA2 with the adaptor protein complex 4 (AP-4) to target them to the somatodendritic compartment of neurons (PubMed:18341993). Interacts with HOOK1 and HOOK2; the interactions are direct, mediate the interaction between FTS-Hook-FHIP (FHF) complex and AP-4 and the perinuclear distribution of AP-4 (By similarity).|||Belongs to the adaptor complexes medium subunit family.|||Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways. AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system (By similarity). It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons (PubMed:18341993). Within AP-4, the mu-type subunit AP4M1 is directly involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos. The adaptor protein complex 4 (AP-4) may also recognize other types of sorting signal (By similarity).|||Early endosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Agr3 ^@ http://purl.uniprot.org/uniprot/Q8R3W7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AGR family.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in the ciliated cells of the airway epithelium. Not detected in the mucous cells.|||Interacts with LYPD3 and DAG1 (alphaDAG1).|||Knockout mice develop ciliated cells with normal-appearing cilia and histology. However, ciliary beat frequency was lower in airways from knockout mice compared with control mice in presence of calcium (20% lower in the absence of stimulation, 35% lower after ATP stimulation). Knockout mice show reduced mucociliary clearance. Knockout mice do not seem to show endoplasmic reticulum stress response.|||Required for calcium-mediated regulation of ciliary beat frequency and mucociliary clearance in the airway. Might be involved in the regulation of intracellular calcium in tracheal epithelial cells. http://togogenome.org/gene/10090:Vmn1r201 ^@ http://purl.uniprot.org/uniprot/Q8R262 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Sfrp5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J001|||http://purl.uniprot.org/uniprot/Q9WU66 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the secreted frizzled-related protein (sFRP) family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP5 may be involved in determining the polarity of photoreceptor, and perhaps, other cells in the retina.|||The FZ domain is involved in binding with Wnt ligands. http://togogenome.org/gene/10090:Stard4 ^@ http://purl.uniprot.org/uniprot/Q99JV5 ^@ Function|||Induction|||Tissue Specificity ^@ Down-regulated by dietary cholesterol.|||Expressed in most tissues, with highest levels in liver and in kidney.|||Involved in the intracellular transport of cholesterol. Binds cholesterol or other sterols. http://togogenome.org/gene/10090:Wnt11 ^@ http://purl.uniprot.org/uniprot/P48615|||http://purl.uniprot.org/uniprot/Q059Y4|||http://purl.uniprot.org/uniprot/Q3UTY8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Wnt family.|||Expressed during embryogenesis.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||extracellular matrix http://togogenome.org/gene/10090:Ankrd17 ^@ http://purl.uniprot.org/uniprot/Q99NH0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Could play pivotal roles in cell cycle and DNA regulation. Involved in innate immune defense against viruse by positively regulating the viral dsRNA receptors RIGI and IFIH1 signaling pathways. Involves in NOD2- and NOD1-mediated responses to bacteria suggesting a role in innate antibacterial immune pathways too. Could play a central role for the formation and/or maintenance of the blood vessels of the circulation system (PubMed:19619540).|||Cytoplasm|||Deficient mice display embryonic lethality during organogenesis with hemorrhages, impaired vascular smooth muscle cell development, impaired vascular integrity and growth retardation.|||Expressed at 8.0-8.5 dpc in the foregut endoderm and at 9.5 dpc in cells migrating into the septum transversum. At 10.5 dpc, highly expressed exclusively in the fetal liver. From 10.5 dpc, expressed in the developing liver throughout gestation and in neonates. At 17.5 dpc, detected in the dorsal root ganglia of the peripheral nervous system.|||Highly expressed in fetal liver. Detected in adult liver cells, ovarian oocytes, seminiferous tubules of the testes and pelvic region of the kidney. It was not detected in heart, gut, lung, spleen and skeletal muscle. Earliest specific in situ marker of hepatic differentiation during embryogenesis, useful for characterization of inductive events involved in hepatic specification.|||Interacts (via N-terminus) with NOD2. Interacts with CDK2, MCM3, MCM5, MCM7, CDC6 and PCNA. Interacts with MAVS and IFIH1. Interacts (via the second ankyrin repeat cluster) with RIGI.|||Nucleus|||Phosphorylated by CDK2.|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:Or13a20 ^@ http://purl.uniprot.org/uniprot/Q8VGL8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sec24d ^@ http://purl.uniprot.org/uniprot/Q6NXL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SEC23/SEC24 family. SEC24 subfamily.|||COPII-coated vesicle membrane|||Endoplasmic reticulum membrane|||Membrane|||cytosol http://togogenome.org/gene/10090:Raet1e ^@ http://purl.uniprot.org/uniprot/D7F2B6|||http://purl.uniprot.org/uniprot/Q9CZQ6 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Acts as a ligand for KLRK1.|||Belongs to the NKG2D ligand family.|||By retinoic acid.|||Cell membrane|||Glycosylated.|||Membrane http://togogenome.org/gene/10090:S100a3 ^@ http://purl.uniprot.org/uniprot/P62818 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the S-100 family.|||Binds both calcium and zinc. May be involved in calcium-dependent cuticle cell differentiation, hair shaft and hair cuticular barrier formation (By similarity).|||Cytoplasm|||Homodimer and homotetramer for the citrullinated form.|||More than half of the arginine residues undergo citrullination by PAD1 and PAD2. Arg-51 is specifically citrullinated by PAD3 and promotes tetramerization (By similarity).|||Skin specific, specifically expressed in cuticle of pelage follicle. http://togogenome.org/gene/10090:Lpar3 ^@ http://purl.uniprot.org/uniprot/Q544B4|||http://purl.uniprot.org/uniprot/Q9EQ31 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Most abundantly expressed in testes, kidney, and lung, with moderate levels in small intestine, and low levels in heart, stomach, spleen, and adult and perinatal brain. Little or no expression in embryonic brain, liver, or thymus.|||Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins. http://togogenome.org/gene/10090:Asap2 ^@ http://purl.uniprot.org/uniprot/Q7SIG6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activates the small GTPases ARF1, ARF5 and ARF6. Regulates the formation of post-Golgi vesicles and modulates constitutive secretion. Modulates phagocytosis mediated by Fc gamma receptor and ARF6. Modulates PXN recruitment to focal contacts and cell migration (By similarity).|||Binds PXN, ARF1, ARF5, ARF6, PTK2B and SRC.|||Cell membrane|||Cytoplasm|||Golgi stack membrane|||Phosphorylated on tyrosine residues by SRC and PTK2B.|||The conserved Arg-467 in the Arf-GAP domain probably becomes part of the active site of bound small GTPases and is necessary for GTP hydrolysis. http://togogenome.org/gene/10090:Rnf183 ^@ http://purl.uniprot.org/uniprot/Q8QZS5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:29300766). Triggers apoptosis in response to prolonged ER stress by mediating the polyubiquitination and subsequent proteasomal degradation of BCL2L1 (By similarity). May collaborate with FATE1 to restrain BIK protein levels thus regulating apoptotic signaling (By similarity).|||Autoubiquitinated (in vitro).|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Highly expressed in the kidney and testis.|||Interacts with FATE1 (By similarity). Interacts with SEC16A (PubMed:29300766). Interacts with BCL2L1 (By similarity).|||Lysosome membrane|||cis-Golgi network membrane http://togogenome.org/gene/10090:Yipf3 ^@ http://purl.uniprot.org/uniprot/Q3UDR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YIP1 family.|||Cell membrane|||Cytoplasm|||Expressed by splenocytes (at protein level).|||Interacts with YIPF4 and YIPF5.|||Involved in the maintenance of the Golgi structure. May play a role in hematopoiesis (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Exosc3 ^@ http://purl.uniprot.org/uniprot/Q7TQK4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRP40 family.|||Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts with GTPBP1 (By similarity). Interacts with ZC3HAV1 (By similarity). Interacts with DDX17 only in the presence of ZC3HAV1 in an RNA-independent manner (By similarity). Interacts with DHX36; this interaction occurs in a RNase-insensitive manner (By similarity).|||Cytoplasm|||Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC3 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC9 and EXOSC5 (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Rcc1 ^@ http://purl.uniprot.org/uniprot/Q8VE37 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Cytoplasm|||Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP, and thereby plays an important role in RAN-mediated functions in nuclear import and mitosis. Contributes to the generation of high levels of chromosome-associated, GTP-bound RAN, which is important for mitotic spindle assembly and normal progress through mitosis. Via its role in maintaining high levels of GTP-bound RAN in the nucleus, contributes to the release of cargo proteins from importins after nuclear import. Involved in the regulation of onset of chromosome condensation in the S phase. Binds both to the nucleosomes and double-stranded DNA.|||Interacts with RAN. Interacts with KPNA3. Interacts (via N-terminus and RCC1 repeats) with KPNA4. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation.|||N-terminal methylation by METTL11A/NTM1 is required for binding double-stranded DNA and stable chromatin association. Dimethylation produces a permanent positive charge on the amino group, which facilitates electrostatic binding to the phosphate groups on DNA, while inhibiting histone-binding. Methylated tail helps retain RCC1 on chromosomes during nucleotide exchange on Ran.|||Nucleus http://togogenome.org/gene/10090:Zfp639 ^@ http://purl.uniprot.org/uniprot/Q99KZ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds DNA and may function as a transcriptional repressor.|||Interacts with CTNNA2.|||Nucleus http://togogenome.org/gene/10090:Mypop ^@ http://purl.uniprot.org/uniprot/Q8R4U1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with PFN1. Homodimer and heterodimer with PFN1.|||Nucleus|||The proline-rich region is required for PFN1 interaction.|||Transcriptional repressor; DNA-binding protein that specifically recognizes the core sequence 5'-YAAC[GT]G-3'. Dimerization with PFN1 reduces its DNA-binding capacity.|||Ubiquitous. Highly expressed in brain, liver and testis. Moderate expression in heart, lung and skeletal muscle. Low expression in spleen and kidney. http://togogenome.org/gene/10090:Uba2 ^@ http://purl.uniprot.org/uniprot/Q9Z1F9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-activating E1 family.|||Broadly expressed, with highest levels in testis.|||Cytoplasm|||Heterodimer of SAE1 and UBA2/SAE2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with UBE2I (By similarity).|||Nucleus|||Sumoylated with SUMO1 and SUMO2/3 and by UBC9. Sumoylation at Lys-236 inhibits enzymatic activity. Sumoylation at the C-terminal lysine cluster plays an essential role in nuclear trafficking (By similarity).|||The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2 (By similarity). http://togogenome.org/gene/10090:Plpp1 ^@ http://purl.uniprot.org/uniprot/Q61469 ^@ Activity Regulation|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the PA-phosphatase related phosphoesterase family.|||Cell membrane|||Forms functional homodimers and homooligomers that are not required for substrate recognition and catalytic activity (PubMed:14725715). Can also form heterooligomers with PLPP2 and PLPP3 (By similarity).|||Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P (PubMed:8702556, PubMed:10359651, PubMed:10818444, PubMed:10620492, PubMed:15461590, PubMed:19215222). Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (By similarity). Through its extracellular phosphatase activity allows both the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (PubMed:17379599). It is for instance essential for the extracellular hydrolysis of S1P and subsequent conversion into intracellular S1P (PubMed:17379599). Involved in the regulation of inflammation, platelets activation, cell proliferation and migration among other processes (PubMed:15461590, PubMed:17057224). May also have an intracellular activity to regulate phospholipid-mediated signaling pathways (PubMed:17057224).|||Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide.|||Membrane raft|||Moderately, by hydrogen peroxide, calcium ionophore and dexamethasone.|||N-glycosylated (PubMed:8702556, PubMed:10620492). N-linked sugars are of the complex type (PubMed:8702556). N-glycosylation is not required for the phosphatase activity (PubMed:10620492).|||Overexpression elicited a number of phenotypic alteration without affecting several aspects of LPA signaling. Phenotypic abnormalities affect primarily three organs: the liver, the skin, and the reproductive organs. There is a reduction on body size, birth weight, abnormalities in fur growth, and a severely impaired spermatogenesis.|||Widely expressed (PubMed:19215222). Highly expressed in kidney and lung. Almost undetectable in brain, heart, bone, muscle or spleen.|||caveola http://togogenome.org/gene/10090:Bloc1s6 ^@ http://purl.uniprot.org/uniprot/Q9R0C0 ^@ Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BLOC1S6 family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. May play a role in intracellular vesicle trafficking, particularly in the vesicle-docking and fusion process.|||Cytoplasm|||Defects in Pldn are the cause of the pallid (pa) phenotype that is characterized by an altered formation or function of intracellular storage granules in melanocytes, platelets, and lysosomes in kidney. Pallid mice have a prolonged bleeding time owing to the inability of immature platelet dense granules to accumulate normal amounts of ATP, ADP, and serotonin. Pa animals also suffer from pigment dilution, kidney lysosomal enzyme elevation and serum alpha1-antitrypsin activity deficiency. Finally, pallid mice exhibit defects in otolith formation that lead to balance abnormalities.|||Expressed in liver, kidney and spleen (at protein level). Ubiquitously expressed, with the highest expression levels observed in brain, heart, liver and kidney.|||May be due to a competing acceptor splice site.|||May be due to exon 2 skipping.|||Membrane|||Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts with SNAP47 (By similarity). Homodimer. Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts with BLOC1S4, BLOC1S5, DTNBP1/BLOC1S7, F-actin, SNAP25 isoform 1 and STX12.|||Phosphorylated. http://togogenome.org/gene/10090:Gpr182 ^@ http://purl.uniprot.org/uniprot/G3X9R9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lbx1 ^@ http://purl.uniprot.org/uniprot/P52955 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Death at birth. Mice fail to expand their lungs and do not move their abnormally thin limbs.|||Expressed in the developing central nervous system from 10.5 dpc to 16.5 dpc. Expressed in presumptive myogenic cells from 9.5 dpc until 16.5 dpc with highest levels at 10.5-11.5 dpc.|||Expressed in the dorsal part of the spinal cord and hindbrain and in presumptive myogenic cells in lateral regions of differentiating somites.|||Interacts with SKOR1 which acts as a transcriptional corepressor.|||Nucleus|||Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord. http://togogenome.org/gene/10090:Bbc3 ^@ http://purl.uniprot.org/uniprot/Q99ML1 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Bcl-2 family.|||By DNA damage, glucocorticoid treatment, growth factor deprivation and p53 (By similarity). By ER stress in a DDIT3/CHOP-dependent manner.|||Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (By similarity). Promotes partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53, releasing the bound p53/TP53 to induce apoptosis (By similarity). Regulates ER stress-induced neuronal apoptosis (PubMed:21159964, PubMed:22761832).|||Interacts with MCL1 and BCL2A1 (PubMed:18589438, PubMed:18462686). Interacts with BCL2 and BCL2L1/BCL-XL (By similarity). Interacts (via BH3 domain) with NOL3 (via CARD domain); this interaction prevents BBC3 association with BCL2 and results in CASP8 activation (By similarity).|||Mitochondrion|||The BH3 motif is intrinsically disordered in the absence of a binding partner but folds upon binding (PubMed:18589438). Folds when bound to BCL2L1 (By similarity). Also folds when bound to MCL1 (PubMed:18589438). http://togogenome.org/gene/10090:Trio ^@ http://purl.uniprot.org/uniprot/Q0KL02 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cell projection|||Cytoplasm|||Early endosome|||Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases. Involved in coordinating actin remodeling, which is necessary for cell migration and growth (By similarity). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (By similarity). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (PubMed:22666460).|||Interacts with CARMIL1. Interacts with PTPRF/LAR. Interacts with ANKRD26 (By similarity). Interacts with Bassoon/BSN and Piccolo/PCLO (By similarity). Interacts with the cytoplasmic region of the heterodimer formed by NGFR and SORCS2. ProNGF binding mediates dissociation of TRIO from the receptor complex (By similarity).|||The N-terminal DBL/GEF domain specifically catalyzes nucleotide exchange for RAC1, leading to the activation of Jun kinase and the production of membrane ruffles. The second DBL/GEF domain is an exchange factor for rhoa and induces the formation of stress fibers (By similarity).|||Widespread in the brain, with more intense signals in the hippocampus, olfactory bulb, cortical layers and cerebellum. Isoform 2 is predominantly expressed in Purkinje neurons of brain. http://togogenome.org/gene/10090:Lztfl1 ^@ http://purl.uniprot.org/uniprot/Q9JHQ5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LZTFL1 family.|||Cytoplasm|||Highly expressed in testis. Expressed in brain, cerebellum, eye, heart, kidney, liver, lung and trachea. In small intestine, graded expression along the crypt-villus axis with high levels in the villus apex and lower levels in the crypt stem cells (at protein level). Not expressed in skeletal muscle and white adipose tissue.|||In hippocampus, up-regulated by exercise training.|||Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function.|||Self-associates. Interacts with BBS9; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking. http://togogenome.org/gene/10090:Scly ^@ http://purl.uniprot.org/uniprot/Q9JLI6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the decomposition of L-selenocysteine to L-alanine and elemental selenium.|||Homodimer.|||Widely expressed. Present in liver, kidney, testis (at protein level).|||cytosol http://togogenome.org/gene/10090:Serpina1c ^@ http://purl.uniprot.org/uniprot/A0A0R4J0X5|||http://purl.uniprot.org/uniprot/Q00896 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Inhibitor of serine proteases. Can inhibit trypsin and chymotrypsin; relatively ineffective against elastase.|||Murine alpha-1-antitrypsin is represented by a cluster of up to 6 individual Serpina1-related genes. The precise complement of Serpina1-related genes present varies according to the strain of the animal.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity. http://togogenome.org/gene/10090:Ces1e ^@ http://purl.uniprot.org/uniprot/Q3UN14|||http://purl.uniprot.org/uniprot/Q64176 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Endoplasmic reticulum lumen|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes retinyl esters.|||Microsome membrane http://togogenome.org/gene/10090:Cox11 ^@ http://purl.uniprot.org/uniprot/Q6P8I6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COX11/CtaG family.|||Exerts its effect at some terminal stage of cytochrome c oxidase synthesis, probably by being involved in the insertion of the copper B into subunit I.|||Interacts with CNNM4/ACDP4. Interacts with RANBP2.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Rab27b ^@ http://purl.uniprot.org/uniprot/Q549X4|||http://purl.uniprot.org/uniprot/Q99P58 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Endosome|||Expressed abundantly in the stomach and is predominantly localized at the apical region of gastric-surface mucus cells. Also expressed in the brain and spleen.|||Interacts with SYTL2, SYTL4, MYRIP and MLPH. Interacts with RPH3A and RPH3A. Interacts (GDP-bound form preferentially) with DENND10 (By similarity).|||Late endosome|||Membrane|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Activated by GEFs such as DENND10.|||Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion (By similarity). Plays a role in NTRK2/TRKB axonal anterograde transport by facilitating the association of NTRK2/TRKB with KLC1 (By similarity). May be involved in targeting uroplakins to urothelial apical membranes (By similarity). http://togogenome.org/gene/10090:Stard8 ^@ http://purl.uniprot.org/uniprot/Q8K031 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Accelerates GTPase activity of RHOA and CDC42, but not RAC1. Stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate by PLCD1 (By similarity).|||Binds both the SH2 and PTB domains of TNS1.|||focal adhesion http://togogenome.org/gene/10090:Carf ^@ http://purl.uniprot.org/uniprot/Q8VHI4 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a transcriptional activator that mediates the calcium- and neuron-selective induction of BDNF exon III transcription. Binds to the consensus calcium-response element CaRE1 5'-CTATTTCGAG-3' sequence (By similarity).|||Highly expressed in brain and testis.|||Nucleus|||The N-terminus is necessary for DNA-binding. The C-terminus is necessary for transcriptional activation. http://togogenome.org/gene/10090:Gm20842 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Cnot2 ^@ http://purl.uniprot.org/uniprot/A0A1S6GWJ6|||http://purl.uniprot.org/uniprot/E9Q027|||http://purl.uniprot.org/uniprot/Q5CZY5|||http://purl.uniprot.org/uniprot/Q8C5L3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CNOT2/3/5 family.|||Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity; prevents their differentiation towards extraembryonic trophectoderm lineages.|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. In the complex interacts directly with CNOT3. Interacts with NCOR1, NCOR2. HDAC3 and GPS2 (By similarity).|||Cytoplasm|||Expressed in embryonic stem (ES) cells and in inner cell mass (ICM) of the blastocyst.|||Nucleus http://togogenome.org/gene/10090:Ssxb8 ^@ http://purl.uniprot.org/uniprot/B1AY40 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Scrn1 ^@ http://purl.uniprot.org/uniprot/Q9CZC8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ 'Secern' is an archaic English term meaning 'secrete'.|||Belongs to the peptidase C69 family. Secernin subfamily.|||Cytoplasm|||Regulates exocytosis in mast cells. Increases both the extent of secretion and the sensitivity of mast cells to stimulation with calcium (By similarity). http://togogenome.org/gene/10090:Folr2 ^@ http://purl.uniprot.org/uniprot/Q05685 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the folate receptor family.|||Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release (By similarity).|||Cell membrane|||No visible phenotype. http://togogenome.org/gene/10090:Rhbdd2 ^@ http://purl.uniprot.org/uniprot/Q8VEK2 ^@ Caution|||Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although strongly related to the peptidase S54 family, it lacks the conserved active sites, suggesting that it has no peptidase activity.|||Belongs to the peptidase S54 family.|||In the developing eye, already detected at 10.5 dpc. Expression increases from 12.5 though 18.5 dpc in all retinal cells (at protein level). At P1, expressed in a small number of cells at the level of the ganglion cell layer and in the inner edge of the ventricular zone of the retina. The number of expressing cells increases and, by P8 to P11, entirely occupies the ganglion cell layer and inner nuclear layer. At that stage, not detected in the photoreceptor cell bodies of the outer nuclear layer. At P21, expressed in all nuclear layers of the retina, including cones (at protein level).|||Might form homotrimers; these trimers are only formed in retina.|||Widely expressed, including in retina and brain (at protein level), as well as in kidney, testis and ovary. Expressed in all layers of the retina, including inner segments of photoreceptor cells and ganglion cells (at protein level).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Hpx ^@ http://purl.uniprot.org/uniprot/Q91X72 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the hemopexin family.|||Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.|||Expressed by the liver and secreted in plasma.|||Secreted|||The isolated N-terminal domain binds one heme. The full-length protein also binds one heme, but at a different site. The physiological significance of this is not clear (By similarity). http://togogenome.org/gene/10090:Or1e1 ^@ http://purl.uniprot.org/uniprot/Q7TRX9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il12rb1 ^@ http://purl.uniprot.org/uniprot/Q60837 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Dimer or oligomer; disulfide-linked. Interacts with IL12RB2 to form the high affinity IL12 receptor. Heterodimer with IL23R; in presence of IL23. The heterodimer forms the IL23 receptor (By similarity).|||Functions as an interleukin receptor which binds interleukin-12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. Associates also with IL23R to form the interleukin-23 receptor which functions in IL23 signal transduction probably through activation of the Jak-Stat signaling cascade.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Hmga1 ^@ http://purl.uniprot.org/uniprot/A0A338P6E8|||http://purl.uniprot.org/uniprot/A0A338P6F6|||http://purl.uniprot.org/uniprot/P17095|||http://purl.uniprot.org/uniprot/Q3TE85|||http://purl.uniprot.org/uniprot/Q3TVP0|||http://purl.uniprot.org/uniprot/Q566K0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HMGA family.|||Chromosome|||HMG-I/Y bind preferentially to the minor groove of A+T rich regions in double-stranded DNA. It is suggested that these proteins could function in nucleosome phasing and in the 3'-end processing of mRNA transcripts. They are also involved in the transcription regulation of genes containing, or in close proximity to A+T-rich regions.|||Interacts with HIPK2.|||Isoforms HMG-I and HMG-Y can be phosphorylated by HIPK2. Phosphorylation may modulate DNA-binding affinity (By similarity).|||Methylation at Arg-58 is mutually exclusive with methylation at Arg-60.|||Nucleus http://togogenome.org/gene/10090:Ctsh ^@ http://purl.uniprot.org/uniprot/P49935 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C1 family.|||Composed of a mini chain and a large chain. The large chain may be split into heavy and light chain. All chains are held together by disulfide bonds.|||Important for the overall degradation of proteins in lysosomes.|||Lysosome|||Mice exhibit markedly abnormal posterior chamber of eyeball with a configuration suggestive of increased axial lengthening, compared to the rounded appearance in wild-type littermates.|||Widely expressed with highest expression found in non-skeletal tissues. Low levels found in skeletal tissue. http://togogenome.org/gene/10090:Atcay ^@ http://purl.uniprot.org/uniprot/Q8BHE3 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cleaved by CASP3 and CASP7. The potential C-terminal product released by CASP3 cleavage may inhibit the ERK signaling pathway through MAP2K2.|||Cytoplasm|||Defects in Atcay are the cause of jittery phenotype, which is characterized by severe truncal and limb ataxia and death due to starvation and dehydration by 3-4 weeks of age.|||Expressed in embryo, where it is also completely restricted to neuronal tissues, including brain, dorsal root ganglia and enteric nervous system. MRNA and protein expressions are not correlated during development.|||Functions in the development of neural tissues, particularly the postnatal maturation of the cerebellar cortex. May play a role in neurotransmission through regulation of glutaminase/GLS, an enzyme responsible for the production in neurons of the glutamate neurotransmitter. Alternatively, may regulate the localization of mitochondria within axons and dendrites.|||Interacts with KLC1; may link mitochondria to KLC1 and regulate mitochondria localization into neuron projections. Interacts with GLS; the interaction is direct and may control GLS localization, negatively regulating its activity. Interacts with PIN1 (via WW domain); upon NGF stimulation (By similarity). The interaction with PIN1 and GLS is competitive (By similarity).|||May be ubiquitinated by STUB1.|||Mitochondrion|||Neuronal tissues specific. Strongly expressed in brain. Expressed in virtually all parts of the adult brain, including cortex, cerebellum and olfactory bulbs. Enriched in hippocampus, cerebellar cortex, deep cerebellar nuclei, and pontine nuclei (at protein level).|||Presynapse|||The CRAL-TRIO domain is known to bind small hydrophobic molecules.|||axon|||dendrite|||growth cone http://togogenome.org/gene/10090:Ftsj1 ^@ http://purl.uniprot.org/uniprot/Q8CBC7 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. TRM7 subfamily.|||Cytoplasm|||Interacts with WDR6; the interaction is direct, and required for 2'-O-methylation of position 34 in substrate tRNAs.|||Leads to a reduction in the level of tRNA(Phe(GAA)) in the brain, but not in the liver, kidney or testis (PubMed:33771871). The levels of tRNA(Leu(CAA)) and tRNA(Leu(UAA)) appear normal in the brain, liver, kidney and testis (PubMed:33771871). Impairs long-term potentiation and long-term depression in the hippocampus (PubMed:33771871, PubMed:36101392). Causes immature spine formation in hippocampal and cortical neurons, with an increase in thin dendritic spines and in the striatal neurons, with an increase in the immature filopodia-like spines (PubMed:33771871, PubMed:36101392). Decreases length and width of the postsynaptic density (PSD) of hippocampal and cortical neurons (PubMed:33771871). Leads to a reduction in the apical layer of the hippocampal CA1 area (PubMed:36101392). Slows spatial learning, impairs fear-conditioning and affects anxiety-like behaviors (PubMed:30557699, PubMed:33771871). Reduces blood sugar levels and platelet count, and decreases levels of alpha-amylase, cholesterol, triglycerides and creatinine (PubMed:30557699). Increases blood corticosterone levels (PubMed:30557699). Leads to a slight reduction in body size and weight (PubMed:30557699, PubMed:33771871).|||Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs (PubMed:33771871). Requisite for faithful cytoplasmic translation (PubMed:33771871). Requires THADA for methylation of the cytidine at position 32 of the anticodon loop of substrate tRNAs (By similarity). Requires WDR6 for methylation of the nucleotide at position 34 of the anticodon loop of substrate tRNAs (By similarity). Promotes translation efficiency of the UUU codon (PubMed:33771871). Plays a role in neurogenesis (PubMed:33771871, PubMed:36101392). Required for expression of genes involved in neurogenesis and mitochondrial translation and energy generation (PubMed:30557699, PubMed:33771871, PubMed:36101392). Requisite for RNA-mediated gene silencing (By similarity). May modify position 32 in tRNA(Arg(ACG)), tRNA(Gln(CUG)), tRNA(Leu(UAA)), tRNA(Leu(UAG)), tRNA(Leu(AAG)), tRNA(Leu(CAG)), tRNA(Phe(GAA)), tRNA(Trp(CCA)) and tRNA(Val(AAC)), and position 34 in tRNA(Phe(GAA)), tRNA(Leu(CAA)), tRNA(Leu(UAA)), tRNA(Sec(UCA)), and tRNA(Trp(CCA)) (PubMed:33771871).|||Nucleus|||Probable cloning artifact. http://togogenome.org/gene/10090:Or6c2 ^@ http://purl.uniprot.org/uniprot/Q8VGJ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ucp2 ^@ http://purl.uniprot.org/uniprot/P70406|||http://purl.uniprot.org/uniprot/Q549J5 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiporter that exports dicarboxylate intermediates of the Krebs cycle in exchange for phosphate plus a proton across the inner membrane of mitochondria, a process driven by mitochondrial motive force with an overall impact on glycolysis, glutaminolysis and glutathione-dependent redox balance. Continuous export of oxaloacetate and related four-carbon dicarboxylates from mitochondrial matrix into the cytosol negatively regulates the oxidation of acetyl-CoA substrates via the Krebs cycle lowering the ATP/ADP ratio and reactive oxygen species (ROS) production (By similarity). Proton transporter activity is debated, but if it occurs it may mediate inducible proton re-entry into the mitochondrial matrix affecting ATP turnover as a protection mechanism against oxidative stress. Proton re-entry may be coupled to metabolite transport to allow for proton flux switching and optimal ATP turnover (PubMed:12011051, PubMed:11756659) (By similarity). Regulates the use of glucose as a source of energy. Required for glucose-induced DRP1-dependent mitochondrial fission and neuron activation in the ventromedial nucleus of the hypothalamus (VMH). This mitochondrial adaptation mechanism modulates the VMH pool of glucose-excited neurons with an impact on systemic glucose homeostasis (PubMed:26919426). Regulates ROS levels and metabolic reprogramming of macrophages during the resolution phase of inflammation. Attenuates ROS production in response to IL33 to preserve the integrity of the Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (PubMed:34644537). Can unidirectionally transport anions including L-malate, L-aspartate, phosphate and chloride ions (By similarity). Does not mediate adaptive thermogenesis (PubMed:11101840).|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Down-regulated upon macrophage stimulation with LPS.|||Homotetramer. Adopts an asymmetrical dimer of dimers functional form.|||Membrane|||Mitochondrion inner membrane|||Mutant mice are viable, have normal postnatal development and show normal thermogenesis in response to cold and diet (PubMed:11101840). They develop glucose intolerance through reduced insulin sensitivity in peripheral organs (PubMed:26919426). Deficient mice are resistant to infection by intracellular parasite Toxoplasma gondi likely due to increased macrophage ROS production (PubMed:11101840).|||The role of UCP2/SLC25A8 in mitochondrial proton transport is a matter of debate. It was initially suggested that it mediates proton leak that increases net proton conductance in response to ROS such as reactive alkenals generated during fatty acid oxidation in mitochondria. By lowering the proton motive force, it would provide for feedback control of mitochondrial ROS metabolism limiting extensive ROS production and protecting cells against oxidative stress. This activity and its potential regulation by ubiquinones and nucleotides was disputed by later studies, which failed to reproduce the effect on proton conductance under physiological conditions. Rather than 'uncoupling' the link between electron transfer and ATP synthesis, it may couple metabolite transport to proton re-entry to allow for proton flux switching and optimal ATP turnover.|||Widely expressed. Highest in spleen, lung, white and brown adipose tissues (PubMed:9133562, PubMed:12011051, PubMed:11101840). 4-6 times higher levels are detected in white adipose tissue of ob/ob and db/db mice when compared to lean littermates (PubMed:9133562). Expressed in neurons of the ventromedial nucleus of the hypothalamus (at protein level) (PubMed:26919426). Expressed in thymocytes (at protein level) (PubMed:11756659). http://togogenome.org/gene/10090:Tesk1 ^@ http://purl.uniprot.org/uniprot/O70146 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autophosphorylation on Ser-215. Kinase activity is inhibited by SPRED1.|||Autophosphorylated on serine and tyrosine residues.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cytoplasm|||Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues (By similarity). Regulates the cellular cytoskeleton by enhancing actin stress fiber formation via phosphorylation of cofilin and by preventing microtubule breakdown via inhibition of TAOK1/MARKK kinase activity (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (PubMed:30115939). Positively regulates integrin-mediated cell spreading, via phosphorylation of cofilin (By similarity). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of ciliary vesicle directional trafficking to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (By similarity). Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity).|||Expressed in testes and brain (at protein level).|||Interacts (via both C- and N-termini) with SPRY4 (via C-terminus); the interaction inhibits TESK1 kinase activity (By similarity). Interacts with TAOK1; the interaction inhibits TAOK1 kinase activity (By similarity). Interacts (via C-terminus) with SPRED1 (via C-terminus); the interaction inhibits TESK1 kinase activity (By similarity). Interacts (via C-terminus) with PARVA/PARVIN (via C-terminus); the interaction inhibits TESK1 kinase activity (By similarity). Interacts with YWHAB/14-3-3 beta; the interaction is dependent on the phosphorylation of TESK1 Ser-439 and inhibits TESK1 kinase activity (By similarity). Interacts with SPRY1, SPRY3 and SPRED2 (By similarity). Interacts (via C-terminus) with SPRY2 (via C-terminus); the interaction disrupts SPRY2 interaction with PPP2CA/PP2A-C, possibly by vesicular sequestration of SPRY2 (PubMed:17974561). Therefore dephosphorylation of SPRY2 by the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme is lost, inhibiting its interaction with GRB2 (By similarity).|||The extracatalytic C-terminal part is highly rich in proline residues.|||centrosome|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Akr1c14 ^@ http://purl.uniprot.org/uniprot/Q91WT7 ^@ Similarity ^@ Belongs to the aldo/keto reductase family. http://togogenome.org/gene/10090:Cebpa ^@ http://purl.uniprot.org/uniprot/P53566 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, expressed in the chorionic plate. From 10.5 to at least 11.5 dpc, is also expressed in the trophoblasts of the labyrinthine layer.|||Belongs to the bZIP family. C/EBP subfamily.|||Binds DNA as a homodimer and as a heterodimer. Can form stable heterodimers with CEBPB, CEBPD, CEBPE and CEBPG (By similarity). Interacts with PRDM16 (PubMed:19641492). Interacts with UBN1 (By similarity). Interacts with ZNF638; this interaction increases transcriptional activation (PubMed:21602272). Interacts with the complex TFDP2:E2F1; the interaction prevents CEBPA binding to target gene promoters and represses its transcriptional activity (By similarity). Interacts with RB1 (PubMed:15107404). Interacts (when phosphorylated at Ser-193) with CDK2, CDK4, E2F4 and SMARCA2 (PubMed:15107404). Interacts with SREBPF1 (PubMed:17290224). Interacts with FOXO1 (via the Fork-head domain); the interaction increases when FOXO1 is deacetylated (PubMed:17090532, PubMed:17627282). Interacts with SIX1 (PubMed:27923061). Interacts (via recognition sequence) with TRIB1 (By similarity). Interacts (via bZIP domain) with OVOL2 (via zinc-finger domains); the interaction inhibits the transcription factor activity of CEBPA and is required to repress adipogenesis (PubMed:36228616).|||Can act as dominant-negative. Binds DNA and have transctivation activity, even if much less efficiently than isoform 2. Does not inhibit cell proliferation.|||Directly and specifically enhances ribosomal DNA transcription interacting with RNA polymerase I-specific cofactors and inducing histone acetylation.|||Interacts with TAF1A and UBTF (By similarity). Interacts with NPM1 (By similarity).|||Interacts with TAF1A and UBTF.|||Isoform 2 and isoform 3 are expressed in adipose tissue and liver (at protein level).|||Mutants die of hypoglycemia at 7-10 hours after birth. They have defects in the control of hepatic growth and lung development. The liver architecture is disturbed with acinar formation. They show hyperproliferation of type II pneumocytes and disturbed alveolar architecture. At the molecular level, accumulation of glycogen and lipids in the liver and adipose tissues is impaired, and the mutant animals are severely hypoglycemic (PubMed:8798745). In very few cases (less than 1%) mutants are able to survive up to 4 weeks but they are sevrely retarded in development. At 2 weeks, they are about half the size of their littermates, very thin and with skin problems. Conditional knockout in adults leads to a lack of granulopoiesis in all hematopoietic organs with no mature peripheral blood granulocytes and the presence of >30% immature myeloid cells in the bone marrow, but without anemia or thrombocytopenia. Animals rarely survive 4 to 5 weeks of age due to sepsis as a result of granulocytopenia (PubMed:15589173). Double knockout CEBPA and CEBPB results in embryonic developmental arrest and death at around 10 dpc to 11 dpc, associated with a gross placenta failure (PubMed:15509779).|||Nucleus|||Phosphorylation at Ser-193 is required for interaction with CDK2, CDK4 and SWI/SNF complex leading to cell cycle inhibition. Dephosphorylated at Ser-193 by protein phosphatase 2A (PP2A) through PI3K/AKT signaling pathway regulation (PubMed:15107404). Phosphorylation at Thr-222 and Thr-226 by GSK3 is constitutive in adipose tissue and lung. In liver, both Thr-222 and Thr-226 are phosphorylated only during feeding but not during fasting (PubMed:17290224). Phosphorylation of the GSK3 consensus sites selectively decreases transactivation activity on IRE-controlled promoters (PubMed:17290224).|||Sumoylated, sumoylation blocks the inhibitory effect on cell proliferation by disrupting the interaction with SMARCA2.|||The recognition sequence (54-72) is required for interaction with TRIB1.|||Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta (PubMed:8415748, PubMed:15107404, PubMed:15589173, PubMed:36228616). Binds directly to the consensus DNA sequence 5'-T[TG]NNGNAA[TG]-3' acting as an activator on distinct target genes. During early embryogenesis, plays essential and redundant functions with CEBPB (PubMed:15509779). Essential for the transition from common myeloid progenitors (CMP) to granulocyte/monocyte progenitors (GMP) (PubMed:24367003). Critical for the proper development of the liver and the lung (PubMed:8798745). Necessary for terminal adipocyte differentiation, is required for postnatal maintenance of systemic energy homeostasis and lipid storage (PubMed:1935900, PubMed:8090719). To regulate these different processes at the proper moment and tissue, interplays with other transcription factors and modulators. Down-regulates the expression of genes that maintain cells in an undifferentiated and proliferative state through E2F1 repression, which is critical for its ability to induce adipocyte and granulocyte terminal differentiation. Reciprocally E2F1 blocks adipocyte differentiation by binding to specific promoters and repressing CEBPA binding to its target gene promoters (PubMed:11672531). Proliferation arrest also depends on a functional binding to SWI/SNF complex (PubMed:14660596). In liver, regulates gluconeogenesis and lipogenesis through different mechanisms. To regulate gluconeogenesis, functionally cooperates with FOXO1 binding to IRE-controlled promoters and regulating the expression of target genes such as PCK1 or G6PC1 (PubMed:17627282). To modulate lipogenesis, interacts and transcriptionally synergizes with SREBF1 in promoter activation of specific lipogenic target genes such as ACAS2 (PubMed:17290224). In adipose tissue, seems to act as FOXO1 coactivator accessing to ADIPOQ promoter through FOXO1 binding sites (PubMed:17090532).|||Ubiquitinated by COP1 upon interaction with TRIB1.|||nucleolus http://togogenome.org/gene/10090:Btnl4 ^@ http://purl.uniprot.org/uniprot/A2CG29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Membrane http://togogenome.org/gene/10090:Gpr141 ^@ http://purl.uniprot.org/uniprot/Q7TQP0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Nkap ^@ http://purl.uniprot.org/uniprot/Q9D0F4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional repressor. Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development. Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter (By similarity).|||Belongs to the NKAP family.|||Component of the Notch corepressor complex. Interacts with CIR1 and HDAC3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Pomgnt1 ^@ http://purl.uniprot.org/uniprot/Q91X88 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 13 family.|||Broadly expressed in late embryonic and early postnatal cerebellar neurons, including premigratory granule neurons of the external granule cell layer. Expression is maintained in neurons of the internal granule cell layer after migration is complete. Expressed in Purkinje cells throughout development. Expressed in Bergmann glial scaffolds used by granule cells during early posnatal radial migration.|||Expressed at basal body and daughter centriole of photoreceptor cells (at protein level).|||Golgi apparatus membrane|||Interacts with DAG1 (via O-linked mannose moiety). Interacts (via transmembrane domain) with FKTN; the interaction is direct and is required for normal location in Golgi membranes.|||Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins. Catalyzes the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins, providing the necessary basis for the addition of further carbohydrate moieties. Is specific for alpha linked terminal mannose.|||The GG-type lectin domain is known as the stem domain in POMGnT1. It mediates specific interaction with beta-linked N-acetylglucosamine moieties of O-glycosylated proteins. It also interacts with its product, N-acetyl-beta-D-glucosaminyl-(1->2)-O-alpha-D-mannosylprotein.|||The manganese ion interacts primarily with the substrate UDP-N-acetylglucosamine. http://togogenome.org/gene/10090:Rufy1 ^@ http://purl.uniprot.org/uniprot/Q8BIJ7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in early endosomal trafficking.|||Broadly expressed.|||Cytoplasm|||Early endosome membrane|||Interacts with BMX. May interact with SSB (By similarity). Interacts with RAB4 and RAB5 that have been activated by GTP-binding.|||Phosphorylation on Tyr-393 and/or Tyr-404 is required for interaction with BMX and endosomal targeting.|||The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions (By similarity). http://togogenome.org/gene/10090:Ibtk ^@ http://purl.uniprot.org/uniprot/Q6ZPR6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as an inhibitor of BTK tyrosine kinase activity, thereby playing a role in B-cell development. Down-regulates BTK kinase activity, leading to interference with BTK-mediated calcium mobilization and NF-kappa-B-driven transcription (By similarity).|||Cytoplasm|||Interacts with the PH domain of BTK.|||Membrane http://togogenome.org/gene/10090:Tenm1 ^@ http://purl.uniprot.org/uniprot/A2ANL9|||http://purl.uniprot.org/uniprot/A2ANM0|||http://purl.uniprot.org/uniprot/Q9WTS4 ^@ Caution|||Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tenascin family. Teneurin subfamily.|||Binds to the plasma membrane and may be internalized by a receptor- and caveolae-mediated endocytosis manner to reach cytosolic compartments in a dynamin-dependent manner.|||Cell membrane|||Cytoplasm|||Cytoplasmic proline-rich regions could serve as docking domains for intracellular SH3-containing proteins.|||Derives from the plasma membrane form by proteolytic processing. Further proteolytic cleavage may generate 11.9 and 4.7 kDa bioactive peptides.|||EGF-like domains 2 and 5 which have an odd number of cysteines might enable the formation of intermolecular disulfide bonds.|||Homodimer; disulfide-linked. Heterodimer with either TENM2 or TENM3. May also form heterodimer with TENM4. Ten-1 ICD interacts with SORBS1 (via third SH3 domain). Interacts with MBD1 isoform 2 (PubMed:15777793). Ten-1 ICD interacts with HINT1 (PubMed:31088288).|||Induces gene transcription activation.|||Involved in neural development, regulating the establishment of proper connectivity within the nervous system. May function as a cellular signal transducer (By similarity).|||Isoform 1 and isoform 2 are expressed in hippocampal cells at 14 dpc (at protein level).|||Isoform 1 and isoform 2 are expressed in the brain. Isoform 2 is expressed in the granular layer of the dentate gyrus and the pyramidal layer (Py) of the CA1, CA2 and CA3 of the hippocampus (at protein level). Expressed in the cortex, thalamus, CA1, CA2, CA3, dentate gyrus and granular layer of the hippocampus. Weakly expressed in kidney, testis and lung.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Nucleus|||Nucleus matrix|||Nucleus speckle|||Once secreted, may also be cleaved to give rise to the TCAP-1 form.|||Plays a role in the regulation of neuroplasticity in the limbic system. Mediates a rapid reorganization of actin- and tubulin-based cytoskeleton elements with an increase in dendritic arborization and spine density formation of neurons in the hippocampus and amygdala. Induces BDNF transcription inhibition in neurons. Activates the mitogen-activated protein (MAP) kinase 2 (MEK2) and extracellular signal-regulated kinase (ERK) cascade. Acts also as a bioactive neuroprotective peptide on limbic neurons of the brain and regulates stress-induced behavior: attenuates alkalosis-associated necrotic cell death and the effects of corticotropin-releasing factor (CRF) on c-fos/FOS induction and on the reinstatement of cocaine seeking.|||Secreted|||cytoskeleton http://togogenome.org/gene/10090:Atf5 ^@ http://purl.uniprot.org/uniprot/O70191 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-29 by EP300, the acetylation enhances the interaction with CEBPB, DNA-binding and transactivation activity.|||Belongs to the bZIP family.|||Binds DNA as a dimer. Interacts with PTP4A1/PRL-1 (By similarity). Interacts with CCND3, but not with CCND1 or CCND2. Interacts with HSPA1A or HSPA1B; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes. Interacts (via C-terminal region) with NPM1 (via C-terminal region); the interaction leads to loss of association between HSPA1A or HSPA1B and ATF5 and promotes ATF5 degradation via proteasome-dependent and caspase-dependent processes. Interacts with NLK; the interaction stabilizes ATF5 at the protein level in a kinase-independent manner. Interacts with alpha-tubulin, gamma-tubulin members TUBGCP2 and TUBGCP4, PCNT; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome (By similarity). Interacts with CEBPB and EP300; EP300 is required for ATF5 and CEBPB interaction and DNA binding (PubMed:24216764).|||Cytoplasm|||Expressed in a circadian manner in the liver. Down-regulated by pro-apoptotic stimuli such IL3-deprivation that induce LCN2 expression (PubMed:12130540). In neural stem cells the expression is induced by retinoic acid (PubMed:23090999).|||Expressed in sensory neurons during embryonic development of the olfactory epithelium and vomeronasal organ. From, at least, 11.5 dpc through adulthood, expressed in the olfactory system. At 14.5 dpc, highly expressed in the olfactory epithelia, vomeronasal organ, the Grueneberg ganglion, the septal organ and the olfactory bulb (PubMed:23090999). At 14.5 dpc, expressed within germinal regions in the ventricular zone of the brain, the rhombic lip and the nascent external granule layer (EGL). At 16.5 dpc expression at the EGL is more intense and extensive. From P1 to P15, expressed in cerebellar granule neuron progenitor cells (CGNPs) of the EGL (PubMed:22095825).|||Highly expressed in liver and at lower levels in heart, brain, lung, kidney, adipose tissue, and skeletal muscle. Expressed in some immature and in all mature olfactory sensory neurons (at protein level) (PubMed:23090999).|||Nucleus|||Phosphorylated by NLK, probably at Ser-92 and Ser-126.|||The majority of pups die within 48h after birth even if there is no major phenotypic differences at birth. Mice reveal a lack of milk in their stomach and show a dramatic loss of mature olfactory sensory neurons.|||Transcription factor that either stimulates or represses gene transcription through binding of different DNA regulatory elements such as cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), ATF5-specific response element (ARE) (consensus: 5'-C[CT]TCT[CT]CCTT[AT]-3') but also the amino acid response element (AARE), present in many viral and cellular promoters. Critically involved, often in a cell type-dependent manner, in cell survival, proliferation, and differentiation. Its transcriptional activity is enhanced by CCND3 and slightly inhibited by CDK4 (By similarity). Important regulator of the cerebral cortex formation, functions in cerebral cortical neuroprogenitor cells to maintain proliferation and to block differentiation into neurons. Must be down-regulated in order for such cells to exit the cycle and differentiate. Participates in the pathways by which SHH promotes cerebellar granule neuron progenitor cells proliferation (PubMed:22095825). Critical for survival of mature olfactory sensory neurons (OSN), directs expression of OSN-specific genes (PubMed:23090999). May be involved in osteogenic differentiation. Promotes cell proliferation and survival by inducing the expression of EGR1 sinergistically with ELK1. Once acetylated by EP300, binds to ARE sequences on target genes promoters, such as BCL2 and EGR1 (By similarity). Plays an anti-apoptotic role through the transcriptional regulation of BCL2, this function seems to be cell type-dependent (By similarity) (PubMed:12130540). Cooperates with NR1I3/CAR in the transcriptional activation of CYP2B6 in liver. In hepatic cells, represses CRE-dependent transcription and inhibits proliferation by blocking at G2/M phase. May act as a negative regulator of IL1B transduction pathway in liver. Upon IL1B stimulus, cooperates with NLK to activate the transactivation activity of C/EBP subfamily members. Besides its function of transcription factor, acts as a cofactor of CEBPB to activate CEBPA and promote adipocyte differentiation. Regulates centrosome dynamics in a cell-cycle- and centriole-age-dependent manner. Forms 9-foci symmetrical ring scaffold around the mother centriole to control centrosome function and the interaction between centrioles and pericentriolar material (By similarity).|||Ubiquitinated by CDC34 and UBE2B in order to be degraded by the proteasome. Cisplatin inhibits ubiquitination and proteasome-mediated degradation by inhibiting the interaction with CDC34. Ubiquitination and degradation by the proteasome are inhibited by NLK in a kinase-independent manner.|||centrosome http://togogenome.org/gene/10090:Pex11b ^@ http://purl.uniprot.org/uniprot/Q9Z210 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxin-11 family.|||Homodimer. Heterodimer with PEX11G. Interacts with PEX19. Interacts with FIS1.|||Involved in peroxisomal proliferation. May regulate peroxisome division by recruiting the dynamin-related GTPase DNM1L to the peroxisomal membrane. Promotes membrane protrusion and elongation on the peroxisomal surface.|||Mice have a marked decrease in peroxisome abundance. They share several phenotypes with Zellweger syndrome mouse models, including neuronal migration defects, hypotonia, a developmental delay, and neonatal lethality but no detectable defect in peroxisomal protein import and only mild defects in peroxisomal metabolic function.|||Peroxisome membrane http://togogenome.org/gene/10090:Itpr3 ^@ http://purl.uniprot.org/uniprot/P70227 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the InsP3 receptor family.|||Endoplasmic reticulum membrane|||Homotetramer. Interacts with TRPC1, TRPC3, TRPC4. Interacts with TRPV4 (By similarity). Interacts with SIGMAR1 (PubMed:11149946). Interacts with AKT1 and PML (PubMed:21030605). Interacts with IRAG2 (via coiled-coil domain) (PubMed:20071408). Interacts with CABP1 (By similarity). Interacts with TMBIM4/LFG4 (By similarity). Interacts with CEMIP (By similarity). Interacts with TESPA1 (PubMed:23650607). Interacts with TMEM203 (By similarity). Interacts with BOK; regulates ITPR3 expression (By similarity). Interacts with BCL2L10 (By similarity).|||Phosphorylated on tyrosine residues (By similarity). Phosphorylated by AKT1 on serine and/or threonine residues.|||Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. Involved in cellular calcium ion homeostasis (By similarity).|||The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region. http://togogenome.org/gene/10090:Skint3 ^@ http://purl.uniprot.org/uniprot/A7TZF0 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin and thymus.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Synm ^@ http://purl.uniprot.org/uniprot/A0A140LJ61|||http://purl.uniprot.org/uniprot/Q70IV5 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 11.5 dpc, isoform 1 and isoform 2 are widely expressed in the developing nervous and vascular systems and are also found specifically associated with vimentin in endothelial cells. By 15 dpc, isoform 1, isoform 2 and isoform 3, are found coexpressed with neurofilament, peripherin and internexin in the peripheral nervous system (at protein level). In the developing embryo, isoform 2 is detected as early as 5 dpc, whereas isoform 1 is first observed at 9 dpc in the nervous system and mesodermic derivatives. Isoform 3 is observed later in neurons at 15 dpc.|||Belongs to the intermediate filament family.|||Interacts with DES, DMD, DTNA, TLN1, UTRN and VCL (By similarity). Isoform 1 and isoform 2 interact with GFAP and VIM.|||Isoform 2 and isoform 3 are detected in adult skeletal muscle, heart and bladder, whereas isoform 1 is only detected in adult bladder (at protein level).|||Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells (By similarity).|||Up-regulated in reactive astrocytes following neurotrauma (at protein level).|||adherens junction|||cytoskeleton http://togogenome.org/gene/10090:Mlf1 ^@ http://purl.uniprot.org/uniprot/Q3V042|||http://purl.uniprot.org/uniprot/Q8JZS2|||http://purl.uniprot.org/uniprot/Q9QWV4 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MLF family.|||Cytoplasm|||Expression is activated by FOXJ1.|||Highly expressed in skeletal muscle, heart, testis. Also found in lung, but not in spleen, thymus, bone marrow, liver and kidney.|||Interacts with CENPU (By similarity). Also interacts with NRBP1/MADM, YWHAZ/14-3-3-zeta and HNRPUL2/MANP. NRBP1 recruits a serine kinase which phosphorylates both itself and MLF1. Phosphorylated MLF1 then binds to YWHAZ and is retained in the cytoplasm. Retained in the nucleus by binding to HNRPUL2. Binds to COPS3/CSN3 which is required for suppression of COP1 and activation of p53.|||Involved in lineage commitment of primary hemopoietic progenitors by restricting erythroid formation and enhancing myeloid formation. Interferes with erythropoietin-induced erythroid terminal differentiation by preventing cells from exiting the cell cycle through suppression of CDKN1B/p27Kip1 levels. Suppresses COP1 activity via CSN3 which activates p53 and induces cell cycle arrest. Binds DNA and affects the expression of a number of genes so may function as a transcription factor in the nucleus.|||Nucleus|||Phosphorylation is required for binding to YWHAZ.|||cilium|||cilium basal body http://togogenome.org/gene/10090:Stat1 ^@ http://purl.uniprot.org/uniprot/A0A087WSP5|||http://purl.uniprot.org/uniprot/Q8C3V4|||http://purl.uniprot.org/uniprot/Q8C497|||http://purl.uniprot.org/uniprot/Q8C8M3|||http://purl.uniprot.org/uniprot/Q8CFQ1|||http://purl.uniprot.org/uniprot/Q99K94 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the transcription factor STAT family.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Hcfc2 ^@ http://purl.uniprot.org/uniprot/Q9D968 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds KMT2A/MLL1. Component of the MLL1/MLL complex, at least composed of KMT2A/MLL1, ASH2L, RBBP5, DPY30, WDR5, MEN1, HCFC1 and HCFC2 (By similarity). Interacts with TASOR (PubMed:31112734).|||Cytoplasm|||Expressed in the spermatogonia, spermatocytes and ovary.|||Nucleus http://togogenome.org/gene/10090:Tank ^@ http://purl.uniprot.org/uniprot/P70347 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein involved in I-kappa-B-kinase (IKK) regulation which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity. Acts as a regulator of TRAF function by maintaining them in a latent state. Blocks TRAF2 binding to LMP1 and inhibits LMP1-mediated NF-kappa-B activation. Negatively regulates NF-kappaB signaling and cell survival upon DNA damage. Plays a role as an adapter to assemble ZC3H12A, USP10 in a deubiquitination complex which plays a negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage. Promotes UBP10-induced deubiquitination of TRAF6 in response to DNA damage. May control negatively TRAF2-mediated NF-kappa-B activation signaled by CD40, TNFR1 and TNFR2. Essential for the efficient induction of IRF-dependent transcription following infection with Sendai virus.|||Cytoplasm|||Heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Homodimer (By similarity). Found in a deubiquitination complex with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta-mediated NF-kappaB activation by promoting IKBKG or TRAF6 deubiquitination (By similarity). Interacts with IKBKG; this interaction increases in response to DNA damage (By similarity). Interacts with TRAF6; this interaction increases in response to DNA damage and recruits USP10 to the ubiquitinated TRAF6 (By similarity). Interacts with USP10; this interaction increases in response to DNA damage (By similarity). Interacts with TBK1 and IKBKE (By similarity). Interacts also with TRAF1, TRAF2, and TRAF3 by binding to their TRAF-C domains; the interaction with TRAF2 is disrupted by the phosphorylation of TANK by IKBKE (By similarity). Interacts more strongly with TRAF1 and TRAF2 than TRAF3 (By similarity). Part of a ternary complex consisting of TANK, IKBKB and IKBKG (By similarity). Interacts with IKBKG; the interaction is enhanced by IKBKE and TBK1 (PubMed:12133833). http://togogenome.org/gene/10090:Cryab ^@ http://purl.uniprot.org/uniprot/P23927|||http://purl.uniprot.org/uniprot/Q52L78 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small heat shock protein (HSP20) family.|||Heteromer composed of three CRYAA and one CRYAB subunits. Aggregates with homologous proteins, including the small heat shock protein HSPB1, to form large heteromeric complexes. Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens (By similarity). Interacts with HSPBAP1 (PubMed:10751411). Interacts with TTN/titin. Interacts with TMEM109; in the cellular response to DNA damage. Interacts with DES; binds rapidly during early stages of DES filament assembly and a reduced binding seen in the later stages. Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (By similarity). Interacts with ATP6V1A and with MTOR, forming a ternary complex (PubMed:31786107).|||Lens as well as other tissues.|||Lysosome|||May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions.|||May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. In lens epithelial cells, stabilizes the ATP6V1A protein, preventing its degradation by the proteasome (PubMed:31786107).|||Nucleus|||Secreted|||Up-regulated by HSF4.|||cytosol http://togogenome.org/gene/10090:Steap2 ^@ http://purl.uniprot.org/uniprot/B2RX33|||http://purl.uniprot.org/uniprot/D3YUM6|||http://purl.uniprot.org/uniprot/Q8BWB6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the STEAP family.|||Cell membrane|||Endosome membrane|||Integral membrane protein that functions as NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane (PubMed:16609065). Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (By similarity). Can also reduce Cu(2+) to Cu(1+) (PubMed:16609065).|||Membrane http://togogenome.org/gene/10090:Thoc2 ^@ http://purl.uniprot.org/uniprot/B1AZI6|||http://purl.uniprot.org/uniprot/Q3US09 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the THOC2 family.|||Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with THOC1, POLDIP3 and ZC3H11A (By similarity).|||Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with THOC1, POLDIP3 and ZC3H11A.|||Expressed in the hippocampus and the cortical neurons.|||Nucleus|||Nucleus speckle|||Required for efficient export of polyadenylated RNA and spliced mRNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. Plays a role for proper neuronal development. http://togogenome.org/gene/10090:Cnpy3 ^@ http://purl.uniprot.org/uniprot/Q9DAU1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the canopy family.|||Endoplasmic reticulum|||Interacts with HSP90B1; this interaction is disrupted in the presence of ATP. Interacts with TLR1, TLR2, TLR4 and TLR9. Strongest interaction with TLR4.|||The birth rate of knockout mice on a C57BL/6 background is very low (approximately 10% of pups). The animals appear normal, but their growth after birth is severely retarded. Half of them die by the end of the weaning period. Mutant mice have profoundly impaired T-helper type 1 lymphocyte (Th1)-mediated responses (PubMed:17998391). On a BALB/c background, under resting conditions, they show spastic or dystonic features and, during the open field test, they exhibit hyperactivity and anxiety. Their resting electroencephalography show enhanced activity in the fast beta frequency band (20-35 Hz). They do not show any apparent structural brain anomaly (PubMed:29394991).|||Toll-like receptor (TLR)-specific co-chaperone for HSP90B1. Required for proper TLR folding, except that of TLR3, and hence controls TLR exit from the endoplasmic reticulum. Consequently, required for both innate and adaptive immune responses. http://togogenome.org/gene/10090:Piezo1 ^@ http://purl.uniprot.org/uniprot/E9PUQ9 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PIEZO (TC 1.A.75) family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Scn3b ^@ http://purl.uniprot.org/uniprot/H3BJR6|||http://purl.uniprot.org/uniprot/Q0P666|||http://purl.uniprot.org/uniprot/Q8BHK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sodium channel auxiliary subunit SCN3B (TC 8.A.17) family.|||Membrane|||Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with NFASC may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).|||Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with NFASC may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.|||The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1, beta-2, beta-3 and/or beta-4 subunits. Beta-1 and beta-3 are non-covalently associated with alpha, while beta-2 and beta-4 are covalently linked by disulfide bonds (By similarity). http://togogenome.org/gene/10090:Mogat2 ^@ http://purl.uniprot.org/uniprot/Q80W94 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the diacylglycerol acyltransferase family.|||Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. Has a preference toward monoacylglycerols containing unsaturated fatty acids in an order of C18:3 > C18:2 > C18:1 > C18:0. Plays a central role in absorption of dietary fat in the small intestine by catalyzing the resynthesis of triacylglycerol in enterocytes. May play a role in diet-induced obesity. Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (By similarity).|||Endoplasmic reticulum membrane|||Inhibited by oleic acid and sphingosine, while it is stimulated by phosphatidylcholine, phosphatidylserine and phosphatidic acid.|||Mainly expressed in small intestine. Detected in the small intestine in a proximal-to-distal gradient that correlated with fat absorption pattern. Present not only in the villi, but also in the crypt regions of the small intestine, which suggests that expression occurs prior to the maturation of enterocytes. Not detectable in other sections of the digestive tract, including stomach, cecum, colon and rectum, or other tissues such as kidney, liver and adipocytes (at protein level). Also detected in kidney, adipose and stomach. Expressed at very low level in liver, skeletal muscle and spleen. Not expressed in brain, heart, lung, skin, testis and thymus.|||Up-regulated in mice fed a high fat diet, implicating a role in diet-induced obesity (at protein level).|||perinuclear region http://togogenome.org/gene/10090:Or8b56 ^@ http://purl.uniprot.org/uniprot/Q7TRB9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hhip ^@ http://purl.uniprot.org/uniprot/Q7TN16 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A flexible loop interacts with the SHH zinc binding site and contributes to zinc binding.|||Belongs to the HHIP family.|||Cell membrane|||First detected at 8.75 dpc, in the ventral midline of the neural tube and in the ventral medial somites. At 10.5 dpc, expression in the notochord is maintained in the caudal region. Expression is lost in the floor plate, but is retained in the ventral half of the neural tube and in the sclerotome of the adjacent somites. In the midbrain, expression confined to two lateral stripes adjacent to the floor plate. Also expressed in the gut mesenchyme along the length of the gastro-intestinal tract and in the mesenchyme of the posterior half of the limb. Expressed in the underlying mesenchyme of the epithelium of a number of tissues including lung, gut and whisker. Also expressed in the perichondrium and in the androgen-producing interstitial somatic cells of the developing testis.|||In the adult brain, high expression found in the ventral cochlear nucleus, medial habenula, indusium griseum and tenia tecta. Some expression also in the caudate putamen, the nucleus accumbens, the ventral pallidum and in the superficial layers of the superior colliculus.|||Interacts with all three hedgehog family members, SHH, IHH and DHH.|||Modulates hedgehog signaling in several cell types, including brain and lung through direct interaction with members of the hedgehog family. Soluble forms inhibit Shh-induced differentiation in the fibroblast cell line C3H/10T1/2.|||Secreted http://togogenome.org/gene/10090:Heyl ^@ http://purl.uniprot.org/uniprot/Q9DBX7 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HEY family.|||By activation of the Notch signaling pathway.|||Expressed in heart and at lower levels in brain, lung, muscle, ovary and testis.|||Expressed in the presmitic mesoderm, the somites, the developing peripheral nervous system and arterial smooth muscle. Expressed in atrioventricular cushions from 9.5 dpc to 12.5 dpc. Also expressed in developing retina.|||Expression in nascent somites is reduced in mice lacking Notch signaling.|||Interacts with HES1, HDAC1, NCOR1 and SIN3A (By similarity). Self-associates. Interacts with GATA4, GATA6, HEY1 and HEY2.|||Nucleus|||Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (By similarity). Downstream effector of Notch signaling required for cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6. http://togogenome.org/gene/10090:Setbp1 ^@ http://purl.uniprot.org/uniprot/Q9Z180 ^@ Subcellular Location Annotation|||Subunit ^@ Interacts with SET.|||Nucleus http://togogenome.org/gene/10090:Defa24 ^@ http://purl.uniprot.org/uniprot/Q5G865 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Fignl1 ^@ http://purl.uniprot.org/uniprot/Q8BPY9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family.|||Cytoplasm|||Expressed at high level in the testis (PubMed:22110678). Detected in pachytene spermatocytes and in metaphase spermatocytes (at protein level).|||Hexamer. Interacts (via N-terminal one-half region) with RAD51; the interaction is direct. Interacts (via N-terminal one-half region) with SPIDR (via the C-terminal region); the interaction is direct (By similarity). Interacts with FIRRM; may regulate homologous recombination (By similarity).|||Involved in DNA double-strand break (DBS) repair via homologous recombination (HR). Recruited at DSB sites independently of BRCA2, RAD51 and RAD51 paralogs in a H2AX-dependent manner. May regulate osteoblast proliferation and differentiation (PubMed:17352653). May play a role in the control of male meiosis dynamic (PubMed:22110678).|||Nucleus|||The N-terminus is necessary for its recruitment to DNA damage sites.|||perinuclear region http://togogenome.org/gene/10090:Fbxo6 ^@ http://purl.uniprot.org/uniprot/Q9QZN4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with CHEK1 and CUL1 (By similarity). Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with VCP.|||Present in liver and kidney (at protein level). Widely expressed.|||Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. Involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. Ubiquitination of CHEK1 is required to ensure that activated CHEK1 does not accumulate as cells progress through S phase, or when replication forks encounter transient impediments during normal DNA replication (By similarity). Involved in endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Able to recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. Also recognizes sulfated glycans.|||Weakly expressed in embryos. http://togogenome.org/gene/10090:Lin37 ^@ http://purl.uniprot.org/uniprot/Q9D8N6 ^@ Subunit ^@ Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity). http://togogenome.org/gene/10090:Dynlt2a3 ^@ http://purl.uniprot.org/uniprot/P11985 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein light chain Tctex-type family.|||Could be involved in transmission ratio distortion (trd) in mouse t-haplotype which causes male sterility.|||Cytoplasmic granule|||Expressed in testis (at protein level). Expressed at the pachyten stage of the first meiotic division and in later haploid spermatogenic stages.|||Interacts with CSNK2B.|||May be an accessory component of axonemal dynein and cytoplasmic dynein 1. Candidate for involvement in male sterility.|||Membrane|||cytoskeleton http://togogenome.org/gene/10090:Rnf32 ^@ http://purl.uniprot.org/uniprot/Q9JIT1 ^@ Function|||Miscellaneous|||Subcellular Location Annotation ^@ Cytoplasm|||May play a role in sperm formation.|||No coding region alterations in either Hemimelic extra-toes (Hx) or Hammertoe (Hm) mutant mice was detected. http://togogenome.org/gene/10090:Kiss1r ^@ http://purl.uniprot.org/uniprot/B2CP06|||http://purl.uniprot.org/uniprot/C5H7S2|||http://purl.uniprot.org/uniprot/Q91V45 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Highest level in the heart and 15- and 17-day embryos. Low level in other tissues. Colocalized with gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus.|||Membrane|||Receptor for metastin (kisspeptin-52 or kp-52), a C-terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. The receptor is essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/KISS1R system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. Analysis of the transduction pathways activated by the receptor identifies coupling to phospholipase C and intracellular calcium release through pertussis toxin-insensitive G(q) proteins. http://togogenome.org/gene/10090:Nckap5l ^@ http://purl.uniprot.org/uniprot/Q6GQX2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ CDK1/Cyclin B-dependent phosphorylation mediates its dissociation from centrosomes during mitosis.|||Homodimer. Interacts with CDK5RAP2. Interacts with MAPRE1. Interacts with beta-tubulin.|||Regulates microtubule organization and stabilization. Promotes microtubule growth and bundling formation and stabilizes microtubules by increasing intense acetylation of microtubules. Both tubulin-binding and homodimer formation are required for NCKAP5L-mediated microtubule bundle formation.|||centrosome http://togogenome.org/gene/10090:Rhoh ^@ http://purl.uniprot.org/uniprot/Q9D3G9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Inhibits the activation of NF-kappa-B by TNF and IKKB and the activation of CRK/p38 by TNF. Inhibits activities of RAC1, RHOA and CDC42. Negatively regulates leukotriene production in neutrophils (By similarity). Negative regulator of hematopoietic progenitor cell proliferation, survival and migration. Critical regulator of thymocyte development and T-cell antigen receptor (TCR) signaling by mediating recruitment and activation of ZAP70 (PubMed:17028588). Required for phosphorylation of CD3Z, membrane translocation of ZAP70 and subsequent activation of the ZAP70-mediated pathways. Essential for efficient beta-selection and positive selection by promoting the ZAP70-dependent phosphorylation of the LAT signalosome during pre-TCR and TCR signaling. Crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Plays critical roles in mast cell function by facilitating phosphorylation of SYK in Fc epsilon RI-mediated signal transduction. Essential for the phosphorylation of LAT, LCP2, PLCG1 and PLCG2 and for Ca(2+) mobilization in mast cells.|||Cell membrane|||Cytoplasm|||Expressed at all stages of thymocyte development, with relative peaks at the DN3 and DP stages.|||Expression is widespread in hematopoietic cells, including in bone marrow progenitor cells and in differentiated myeloid as well as lymphoid cells. Expressed at high levels in the thymus and mast cells, found in spleen and low-density bone marrow (LDBM) cells and is detected at a low level in neutrophils. In the thymus it is detected in thymocytes of the thymic cortex but not in non-lymphoid cells of fibrovascular and fibroadipose tissues. Expressed in T-cells, B-cells and mast cells.|||Interacts with GDI1 and GDI2 (By similarity). Interacts with ZAP70 (via SH2 domains) and the interaction is enhanced by its phosphorylation by LCK. Interacts with SYK and the interaction is enhanced by its phosphorylation by FYN.|||Knockout mice have smaller thymuses than wild-type animals, and T-cell lymphopenia due to defects in T-cell maturation and population expansion in the thymus (PubMed:17028588). Mice show impaired passive systemic anaphylaxis and histamine release upon challenge with the specific antigen.|||Phosphorylated on tyrosine by LCK. Phosphorylated by FYN. Phosphorylation enhances the interactions with ZAP70 and SYK and is critical for its function in thymocyte development.|||The region involved in interaction with ZAP70 is a non-canonical immunoreceptor tyrosine-based activation motif (ITAM). http://togogenome.org/gene/10090:Sprr4 ^@ http://purl.uniprot.org/uniprot/Q8CGN8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. Involved in UV-induced cornification (By similarity).|||Cross-linked to membrane proteins by transglutaminase.|||Cytoplasm|||cell cortex http://togogenome.org/gene/10090:Cyp2d12 ^@ http://purl.uniprot.org/uniprot/Q8BVD2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Cfap95 ^@ http://purl.uniprot.org/uniprot/Q9CQC3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Highly expressed in the testis. Weakly or not expressed in embryonic stem cells.|||Interacts with MYH9. Interacts with MYH10.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Spdye4b ^@ http://purl.uniprot.org/uniprot/Q8CDE8 ^@ Similarity ^@ Belongs to the Speedy/Ringo family. http://togogenome.org/gene/10090:Oog2 ^@ http://purl.uniprot.org/uniprot/A2A961|||http://purl.uniprot.org/uniprot/Q7TPX8 ^@ Similarity|||Tissue Specificity ^@ Belongs to the PRAME family.|||Expressed in ovary, specifically in oocytes. Detected in follicles with two layers of granulosa cells, and are present in early as well as large antral follicles. http://togogenome.org/gene/10090:Dhfr ^@ http://purl.uniprot.org/uniprot/P00375|||http://purl.uniprot.org/uniprot/Q544T5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dihydrofolate reductase family.|||Cytoplasm|||Homodimer.|||Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway (PubMed:25980602). Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (PubMed:25980602). Binds its own mRNA.|||Mitochondrion http://togogenome.org/gene/10090:Habp2 ^@ http://purl.uniprot.org/uniprot/E9QM92|||http://purl.uniprot.org/uniprot/Q3UEI7|||http://purl.uniprot.org/uniprot/Q3V1J8|||http://purl.uniprot.org/uniprot/Q8K0D2 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cleaves the alpha-chain at multiple sites and the beta-chain between 'Lys-53' and 'Lys-54' but not the gamma-chain of fibrinogen and therefore does not initiate the formation of the fibrin clot and does not cause the fibrinolysis directly. It does not cleave (activate) prothrombin and plasminogen but converts the inactive single chain urinary plasminogen activator (pro-urokinase) to the active two chain form. Activates coagulation factor VII (By similarity).|||Heterodimer; disulfide-linked. Heterodimer of a 50 kDa heavy and a 27 kDa light chain linked by a disulfide bond.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Liver and kidney.|||Proteolytic cleavage at Gly-23 or Met-27 can give rise to the 50 kDa heavy chain and cleavage at Arg-311 or Lys-317 can give rise to the 27 kDa light chain. The heavy chain can undergo further proteolytic cleavage at Arg-168 or Arg-169 to give rise to 2 inactive 26 kDa fragments and the light chain can undergo further proteolytic cleavage at Arg-478 to give rise to inactive 17 kDa and 8 kDa fragments.|||Secreted http://togogenome.org/gene/10090:Ints4 ^@ http://purl.uniprot.org/uniprot/Q8CIM8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 4 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Nucleus http://togogenome.org/gene/10090:Reps2 ^@ http://purl.uniprot.org/uniprot/Q80XA6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with EPN1 (By similarity). Interacts with EPS15 AND EPS15L1 (By similarity). Interacts with RALBP1; can form a ternary complex with activated Ral (RALA or RALB) (By similarity). Interacts with ASAP1; the interaction is direct and this complex can bind paxillin (PubMed:12149250). Also forms a ternary complex with RALBP1 and ASAP1 (By similarity). Interacts with GRB2 (By similarity).|||Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors as part of the Ral signaling pathway (By similarity). By controlling growth factor receptors endocytosis may regulate cell survival (By similarity). Through ASAP1 may regulate cell adhesion and migration (By similarity).|||Tyrosine-phosphorylated upon stimulation of cells with EGF. Phosphorylation on Tyr-residues induces its association with the EGF receptor probably indirectly through an adapter like GRB2. http://togogenome.org/gene/10090:Plekha1 ^@ http://purl.uniprot.org/uniprot/Q8BUL6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane (By similarity).|||Binds to membranes enriched in PtdIns3,4P2 via the C-terminal PH domain.|||Cell membrane|||Cytoplasm|||Interacts with MPDZ and PTPN13.|||Nucleus http://togogenome.org/gene/10090:Vmn1r198 ^@ http://purl.uniprot.org/uniprot/Q8R263 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ly6g6e ^@ http://purl.uniprot.org/uniprot/Q8K1T6 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Believed to act as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro potentiates alpha-3:beta-4-containing nAChRs maximum response by increasing peak current and slowing down receptor desensitization; the activity is dependent on its cell surface localization.|||Cell membrane|||Cell projection|||Cell surface|||Interacts with CHRNA4.|||LY6G6E is a pseudogene in humans.|||O-glycosylated. Contains sialic acid residues. http://togogenome.org/gene/10090:Tmem236 ^@ http://purl.uniprot.org/uniprot/A2ARJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM236 family.|||Membrane http://togogenome.org/gene/10090:Thsd4 ^@ http://purl.uniprot.org/uniprot/Q3UTY6 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16.5 dpc, detected in fibrillar structures in various elastic tissues, including developing dermis, perichondria surrounding cartilages and the vessel walls of aortae (at protein level). At postnatal day 7 (P7), weakly expressed in the early stage dental follicle, but becomes readily detectable in assembled microfibril-like structures during the periodontal ligament-forming stage of the dental follicle and in organized microfibrils in the adult periodontal ligament (P35) (at protein level). Up-regulated in the periodontal ligament during wound healing (at protein level).|||Both isoforms are expressed in the embryo from 7 dpc through 17. Isoform 1 is widely expressed in adult tissues. Isoform 2 is detected in brain, spinal cord, eye, kidney, stomach and uterus. Mainly observed in fibrillar extracellular matrices in elastic tissues (at protein level).|||Isoform 2 interacts with FBN1. Isoform 2 may interact with TGFB1.|||Promotes FBN1 matrix assembly. Attenuates TGFB signaling, possibly by accelerating the sequestration of large latent complexes of TGFB or active TGFB by FBN1 microfibril assembly, thereby negatively regulating the expression of TGFB regulatory targets, such as POSTN.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Nup133 ^@ http://purl.uniprot.org/uniprot/Q8CDZ5|||http://purl.uniprot.org/uniprot/Q8R0G9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleoporin Nup133 family.|||Forms part of the Nup160 subcomplex in the nuclear pore which is composed of NUP160, NUP133, NUP107 and Nup96. This complex plays a role in RNA export and in tethering Nup98 and NUP153 to the nucleus (By similarity).|||Involved in poly(A)+ RNA transport. Involved in nephrogenesis.|||kinetochore|||nuclear pore complex http://togogenome.org/gene/10090:Bap1 ^@ http://purl.uniprot.org/uniprot/Q99PU7 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C12 family. BAP1 subfamily.|||Component of the PR-DUB complex, at least composed of BAP1 and ASXL1. Interacts with BRCA1 (via the RING finger). Interacts (via HBM-like motif) with HCFC1. Interacts (when phosphorylated at Thr-492) with FOXK1. Interacts (when phosphorylated at Thr-492) with FOXK2; leading to recruit the PR-DUB complex and repress FOXK2 target genes.|||Cytoplasm|||Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Does not deubiquitinate monoubiquitinated histone H2B. Acts as a regulator of cell growth by mediating deubiquitination of HCFC1 N-terminal and C-terminal chains, with some specificity toward 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains. Deubiquitination of HCFC1 does not lead to increase stability of HCFC1. Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination. It however does not mediate deubiquitination of BRCA1 and BARD1. Able to mediate autodeubiquitination via intramolecular interactions to couteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration. Acts as a tumor suppressor.|||Has the ability to ability to suppress tumorigenicity when expressed in NCI-H226 cells.|||Highly expressed in mammary glands, testis and ovary. Up-regulated in mammary glands during puberty, pregnancy, and as a result of parity.|||Nucleus|||Ubiquitinated: monoubiquitinated at multiple site of its nuclear localization signal (NLS) BY UBE2O, leading to cytoplasmic retention. Able to mediate autodeubiquitination via intramolecular interactions to couteract cytoplasmic retention. http://togogenome.org/gene/10090:Eps8l2 ^@ http://purl.uniprot.org/uniprot/Q99K30 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EPS8 family.|||Cytoplasm|||Detected in fetal kidney, adrenal gland, salivary gland, stomach, gut, cartilage and skin. Detected in adult ovary, placenta, skin, adrenal gland, salivary gland, kidney, intestine and stomach. Expressed at the tips of cochlear hair cells stereocilia (PubMed:23918390).|||Interacts with ABI1. Part of a complex that contains SOS1, ABI1 and EPS8L2. Associates with F-actin (By similarity).|||Mutant animal have a progressive and severe hearing loss at young adulthood (PubMed:23918390). The generation of receptor potentials in hair cells at lower sound pressure is impaired, which leads to a reduction in auditory nerve responses (PubMed:23918390).|||Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton (By similarity). In the cochlea, is required for stereocilia maintenance in adult hair cells (PubMed:23918390).|||stereocilium http://togogenome.org/gene/10090:Gpr135 ^@ http://purl.uniprot.org/uniprot/A7E1Z8|||http://purl.uniprot.org/uniprot/Q7TQP2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Endosome membrane|||Interacts with MTNR1B. Interacts with ARRB1 and ARRB2 in a spontaneous and agonist-independent manner; leading to the internalization of GPR135 in the endosomal compartment (By similarity).|||Membrane|||Orphan receptor. Has spontaneous activity for beta-arrestin recruitment (By similarity). Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization (By similarity). http://togogenome.org/gene/10090:Rps20 ^@ http://purl.uniprot.org/uniprot/P60867|||http://purl.uniprot.org/uniprot/Q5BLK2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS10 family.|||Component of the 40S small ribosomal subunit.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Cytoplasm|||Polyubiquitinated by ZNF598 via 'Lys-63'-linked ubiquitin chains when a ribosome has stalled, initiating the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide. Deubiquitinated by OTUD3 and USP21, antagonizing ZNF598 activity.|||Ufmylated by UFL1. http://togogenome.org/gene/10090:Bcl6b ^@ http://purl.uniprot.org/uniprot/O88282 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a sequence-specific transcriptional repressor in association with BCL6. Necessary for activation of naive T-cells to antigenic stimulation. May attenuate the regulatory effect of BCL6 on antigenic activation of naive CD4 T-cells by forming a heterodimer with BCL6.|||Amino acids 178-210 are essential for repression activity.|||Associates with BCL6 through the BTB domain.|||Induced in activated lymphocytes.|||Nucleus|||Ubiquitously expressed with higher expression found in heart and lung. http://togogenome.org/gene/10090:Prpf40b ^@ http://purl.uniprot.org/uniprot/Q80W14 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRPF40 family.|||Interacts with the N-terminus of HD.|||May be involved in pre-mRNA splicing.|||Nucleus speckle http://togogenome.org/gene/10090:Tubg1 ^@ http://purl.uniprot.org/uniprot/P83887|||http://purl.uniprot.org/uniprot/Q6F4J1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Interacts with TUBGCP2 and TUBGCP3 (By similarity). Interacts with B9D2 (PubMed:18287022). Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of TUBG1 and CDK5RAP2 (By similarity). Interacts with CIMAP3 (PubMed:20643351). Interacts with SAS6 and NUP62 at the centrosome (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') and HAUS8 (By similarity).|||Phosphorylation at Ser-131 by BRSK1 regulates centrosome duplication, possibly by mediating relocation of gamma-tubulin and its associated proteins from the cytoplasm to the centrosome.|||Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation (By similarity).|||Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.|||centrosome|||spindle http://togogenome.org/gene/10090:Pdap1 ^@ http://purl.uniprot.org/uniprot/Q3UHX2 ^@ PTM|||Similarity ^@ Belongs to the PDAP1 family.|||Phosphorylated by several kinases in vitro. In vivo, can be phosphorylated by CK2. http://togogenome.org/gene/10090:Egfem1 ^@ http://purl.uniprot.org/uniprot/B7ZCE7 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Mrm1 ^@ http://purl.uniprot.org/uniprot/Q99J25 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase TrmH family.|||Mitochondrion matrix|||S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes the formation of 2'-O-methylguanosine at position 1145 (Gm1145) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a universally conserved modification in the peptidyl transferase domain of the mtLSU rRNA. http://togogenome.org/gene/10090:Dydc2 ^@ http://purl.uniprot.org/uniprot/Q9D3X8 ^@ Similarity ^@ Belongs to the dpy-30 family. http://togogenome.org/gene/10090:Amigo2 ^@ http://purl.uniprot.org/uniprot/Q80ZD9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. AMIGO family.|||Binds itself as well as AMIGO1 and AMIGO3.|||Cell membrane|||Highest level in cerebellum, retina, liver, and lung. Lower levels in cerebrum, kidney, small intestine, spleen and testis.|||Nucleus|||Required for depolarization-dependent survival of cultured cerebellar granule neurons. May mediate homophilic as well as heterophilic cell-cell interaction with AMIGO1 or AMIGO3. May contribute to signal transduction through its intracellular domain (By similarity). http://togogenome.org/gene/10090:Ripk4 ^@ http://purl.uniprot.org/uniprot/Q9ERK0 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Cytoplasm|||Expressed at 10.5 dpc at diverse locations including the embryonic forebrain, otic vesicle, branchial arches, primitive gut, and genitourinary system. Transient expression in the ventral neural tube at 12.5 dpc. By 14.5 dpc, strong expression throughout the gastrointestinal tract was observed in the luminal tissues of the esophagus, stomach, duodenum, and intestines, as well as transient expression in the skin. Not expressed in kidney.|||Interacts with PRKCB. Interacts with TRAF1, TRAF2, TRAF3 and TRAF5. Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4.|||Involved in stratified epithelial development (By similarity). It is a direct transcriptional target of TP63. Plays a role in NF-kappa-B activation.|||May be phosphorylated by MAP3K2 and MAP3K3.|||Membrane|||Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.|||Proteolytically cleaved by during Fas-induced apoptosis. Cleavage at Asp-342 and Asp-380.|||Ubiquitously expressed, with an abundant expression in the thymus, bone marrow, pro-B, pre-B and immature B cells and a weak expression in the spleen. http://togogenome.org/gene/10090:Ikbkg ^@ http://purl.uniprot.org/uniprot/O88522 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer; disulfide-linked (By similarity). Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits (PubMed:11080499). The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex (PubMed:11080499). The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65 (PubMed:20622870). Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP (By similarity). Interacts with COPS3, CYLD, NALP2, TRPC4AP and PIDD1 (By similarity). Interacts with ATM; the complex is exported from the nucleus (By similarity). Interacts with TRAF6 (By similarity). Interacts with IKBKE (By similarity). Interacts with TANK; the interaction is enhanced by IKBKE and TBK1 (By similarity). Part of a ternary complex consisting of TANK, IKBKB and IKBKG (PubMed:12133833). Interacts with ZFAND5 (By similarity). Interacts with RIPK2 (By similarity). Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG (By similarity). Interacts with TNFAIP3; the interaction is induced by TNF stimulation and by polyubiquitin (By similarity). Binds (via UBAN region) polyubiquitin; binds both 'Lys-63'-linked and linear polyubiquitin, with higher affinity for linear ubiquitin (PubMed:19303852, PubMed:19854204). Interacts with NLRP10 (By similarity). Interacts with TANK; this interaction increases in response to DNA damage (By similarity). Interacts with USP10; this interaction increases in response to DNA damage (By similarity). Interacts with ZC3H12A; this interaction increases in response to DNA damage (By similarity). Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation (By similarity). Interacts with TRIM29; this interaction induces IKBKG/NEMO ubiquitination and proteolytic degradation (By similarity). Interacts with TRIM13; this interaction leads to IKBKG/NEMO ubiquitination (By similarity). Interacts with ARFIP2 (By similarity). Interacts with RIPK1 (PubMed:31519886). Interacts with (ubiquitinated) BCL10; interaction with polyubiquitinated BCL10 via both 'Lys-63'-linked and linear ubiquitin is required for TCR-induced NF-kappa-B activation (By similarity). Interacts with MARCHF2; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO (PubMed:32935379).|||Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.|||Nucleus|||Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.|||Polyubiquitinated on Lys-278 via 'Lys-63'-linked ubiquitin; the ubiquitination is mediated downstream of NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway (By similarity). Polyubiquitinated on Lys-278 and Lys-302 through 'Lys-63'-linked ubiquitin; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway (By similarity). Monoubiquitinated on Lys-270 and Lys-302; promotes nuclear export (By similarity). Polyubiquitinated through 'Lys-27' by TRIM23; involved in antiviral innate and inflammatory responses (By similarity). Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation (By similarity). Deubiquitinated by USP10 in a TANK-dependent and -independent manner, leading to the negative regulation of NF-kappa-B signaling upon DNA damage (By similarity). Ubiquitinated at Lys-319 by MARCHF2 following bacterial and viral infection which leads to its degradation (By similarity). Polyubiquitinated via 'Lys-29'-linked ubiquitin; leading to lysosomal degradation (By similarity).|||Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:9927690). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways. Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much highr affinity for linear polyubiquitin. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (By similarity).|||Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.|||The leucine-zipper domain and the CCHC NOA-type zinc-fingers constitute the UBAN region and are essential for polyubiquitin binding and for the activation of IRF3. http://togogenome.org/gene/10090:Ifna16 ^@ http://purl.uniprot.org/uniprot/Q810G1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Mbd4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0A8|||http://purl.uniprot.org/uniprot/Q3UGS3|||http://purl.uniprot.org/uniprot/Q9Z2D7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with MLH1.|||Mismatch-specific DNA N-glycosylase involved in DNA repair. Has thymine glycosylase activity and is specific for G:T mismatches within methylated and unmethylated CpG sites. Can also remove uracil or 5-fluorouracil in G:U mismatches. Has no lyase activity. Was first identified as methyl-CpG-binding protein.|||Nucleus http://togogenome.org/gene/10090:Zfp36l2 ^@ http://purl.uniprot.org/uniprot/P23949 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the cytoplasmic CCR4-NOT deadenylase to trigger ARE-containing mRNA deadenylation and decay processes. Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner. Interacts with CNOT6L.|||Cytoplasm|||Expressed in preadipocytes and adipocytes (at protein level) (PubMed:22701344). Expressed at highest level in lymphoid tissues such as thymus, spleen, lung, uterus, ovary, small and large intestine, mammary gland, fat and bone marrow (PubMed:19633199, PubMed:22367205). Expressed at intermediate level in kidney, heart, adrenal, eye and fetal liver (PubMed:19633199). Weakly expressed in brain, skeletal muscle and liver (PubMed:19633199, PubMed:22367205). Expressed through B lymphocyte development (PubMed:27102483). Expressed in superior cervical ganglion (SCG) and dorsal root ganglion (DRG) (PubMed:25505318). Expressed in embryonic stem cells (ESCs) (PubMed:24733888). Expressed in oocytes.|||In embryos, expression is detected at 7 dpc, increases at 9.5 dpc, and then remains constant through 18.5 dpc (PubMed:19633199). Expression in the yolk sac is relatively constant between 10.5 dpc and 18.5 dpc (PubMed:19633199). Placenta expression is also constant throughout development with a slight decrease observed at 18.5 dpc (PubMed:19633199). Expressed in burst-forming unit-erythroid (BFU-E) progenitor cells and down-regulated as erythroid cells differentiate (PubMed:23748442).|||Lethality between 2 weeks of birth, due to pancytopenia (PubMed:19633199). Peripheral blood shows a decrease in red and white cells, hemoglobin, hematocrit and platelets (PubMed:19633199). Yolk sacs from 11.5 dpc and fetal livers from 14.5 dpc display markedly reduced numbers of definitive multilineage and lineage-committed hematopoietic progenitors (PubMed:19633199). Mice lacking the N-terminus (DeltaN-ZFP36L2) display female infertility, with embryos that cannot progress beyond the 2-cell stage of development (PubMed:15342461). Show evidence of axonal and fiber degeneration (PubMed:25505318). Exhibit increased REST mRNA stability and REST protein expression in primary neuronal cells from superior cervical ganglion (SCG) and dorsal root ganglion (DRG) (PubMed:25505318). Mice lacking both ZFP36L2 and ZFP36L1 during thymopoiesis lead to aberrant T cell development and subsequently develop a T-cell acute lymphoblastic leukemia (T-ALL) (PubMed:20622884). Show also higher levels of NOTCH1 mRNA and protein in thymocytes (PubMed:20622884). Conditional knockout mice of both ZFP36L2 and ZFP36L1 in pro-B cells display reduced B lymphocyte number and delayed variable-diversity-joining (VDJ) recombination (PubMed:27102483). Exhibit also increased protein and ARE-containing mRNA expressions of several factors implicated in cell cycle progression in late pre-B cells (PubMed:27102483).|||Nucleus|||Phosphorylated by RPS6KA1 at Ser-480 and Ser-482 upon phorbol 12-myristate 13-acetate (PMA) treatment; this phosphorylation results in dissociation of the CCR4-NOT-deadenylase complex and induces p38 MAPK-mediated stabilization of the low-density lipoprotein (LDL) receptor (LDLR) mRNA (By similarity). Phosphorylation occurs during early preadipocyte differentiation (PubMed:22701344).|||Up-regulated in response to fibroblast growth factor FGF4 in embryonic stem cells (ESCs) in a p38 MAPK-dependent manner (at protein level) (PubMed:24733888). Up-regulated by glucocorticoid agonists, such as dexamethasone (DEX), in burst-forming unit-erythroid (BFU-E) progenitors in a receptor NR3C1-dependent manner (PubMed:23748442). Down-regulated during erythroid cell differentiation (PubMed:23748442). Down-regulated during the conversion from quiescence to activated satellite cells upon muscle injury (PubMed:23046558, PubMed:25815583).|||Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:22701344, PubMed:22367205, PubMed:25505318, PubMed:24830504, PubMed:27102483). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (By similarity). Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:22701344, PubMed:22367205, PubMed:25505318, PubMed:24830504). Promotes ARE-containing mRNA decay of the low-density lipoprotein (LDL) receptor (LDLR) mRNA in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (By similarity). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs) (PubMed:22701344). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA (PubMed:25505318). Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA (PubMed:24830504). Acts as a negative regulator of erythroid cell differentiation: promotes glucocorticoid-induced self-renewal of erythroid cells by binding mRNAs that are induced or highly expressed during terminal erythroid differentiation and promotes their degradation, preventing erythroid cell differentiation (PubMed:19633199, PubMed:23748442). In association with ZFP36L1 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity-joining (VDJ) recombination process and functional immune cell formation (PubMed:27102483). Together with ZFP36L1 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA (PubMed:20622884). http://togogenome.org/gene/10090:Ccl7 ^@ http://purl.uniprot.org/uniprot/A9Z1Z1|||http://purl.uniprot.org/uniprot/Q03366 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic factor that attracts monocytes and eosinophils, but not neutrophils. Augments monocyte anti-tumor activity (By similarity).|||Monomer. Interacts with TNFAIP6 (via Link domain).|||Secreted http://togogenome.org/gene/10090:Farsa ^@ http://purl.uniprot.org/uniprot/Q8C0C7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 2 subfamily.|||Cytoplasm|||Heterotetramer; dimer of two heterodimers formed by FARSA and FARSB. http://togogenome.org/gene/10090:Fbxl14 ^@ http://purl.uniprot.org/uniprot/Q8BID8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Part of a SCF (SKP1-cullin-F-box) ubiquitin-protein ligase complex. Interacts with SKP1 and CUL1. Interacts with SNAI1; the interaction requires the phosphorylation of the two serine residues in the substrate destruction motif D-S-G-X(2,3,4)-S (By similarity).|||Substrate-recognition component of some (SKP1-CUL1-F-box protein)-type E3 ubiquitin-protein ligase complexes. The SCF(FBXL14) complex acts by mediating ubiquitination and subsequent degradation of SNAI1 (By similarity). http://togogenome.org/gene/10090:Smim7 ^@ http://purl.uniprot.org/uniprot/Q5RKS2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMIM7 family.|||Membrane http://togogenome.org/gene/10090:H2ac20 ^@ http://purl.uniprot.org/uniprot/Q149V4|||http://purl.uniprot.org/uniprot/Q64523 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Dcaf12l1 ^@ http://purl.uniprot.org/uniprot/Q8CBW4 ^@ Caution|||Similarity ^@ Belongs to the WD repeat DCAF12 family.|||It is uncertain whether Met-1 or Met-31 is the initiator. http://togogenome.org/gene/10090:Prmt1 ^@ http://purl.uniprot.org/uniprot/Q9JIF0 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-228 and Lys-233 regulates ubiquitination by the SCF(FBXL17) complex. Acetylated at Lys-233 by p300/EP300. Deacetylated at Lys-228 and Lys-233 by SIRT1.|||Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, FMR1, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4, SERBP1, RBM15, FOXO1, CHTOP and MAP3K5/ASK1 (PubMed:15327772, PubMed:19858291). Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation (By similarity). May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway (By similarity). Methylates RBM15, promoting ubiquitination and degradation of RBM15 (By similarity). Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity (PubMed:19858291). Methylates MAP3K5/ASK1 at 'Arg-85' and 'Arg-87' which promotes association of MAP3K5 with thioredoxin and negatively regulates MAP3K5 association with TRAF2, inhibiting MAP3K5 stimulation and MAP3K5-induced activation of JNK (By similarity). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (By similarity). Plays a role in regulating alternative splicing in the heart (PubMed:30321814).|||Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.|||Conditional knockout in cardiomyocytes results in dilated cardiomyopathy in juveniles and death within 60 days of birth with aberrant splicing occurring in a number of genes including Ktn1, Lmo7, Mef2a, Tmed2, Snap23, Sorbs1 and Ttn.|||Cytoplasm|||Expressed in the heart where it is detected in both cardiomyocytes and non-myocytes (at protein level).|||Homodimer and heterodimer with PRMT8. Homooctamer; individual homodimers associates to form a homooctamer. Individual homodimers can associate to form a homohexamer. Interacts with BTG1, BTG2 and IFNAR1. Interacts with ILF3 and SUPT5H. Interacts with and methylates FOXO1, leading to the nuclear retention of FOXO1 and the stimulation of FOXO1 transcriptional activity. Methylation of FOXO1 is increased upon oxidative stress (By similarity). Interacts with NFATC2IP. Interacts with and methylates CHTOP, thereby enabling the interaction of CHTOP with the 5FMC complex. Interacts with and probably methylates ATXN2L (By similarity). Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, PRMT1 and ERH (By similarity). Interacts with DHX9 (via RGG region) (By similarity). Interacts (via N-terminus) with HABP4 (By similarity). Interacts with MAP3K5/ASK1; the interaction results in MAP3K5 methylation by PRMT1 which inhibits MAP3K5 activation (By similarity). Interacts with TRIM48; the interaction results in ubiquitination of PRMT1 by TRIM48, leading to PRMT1 proteasomal degradation and activation of MAP3K5 (By similarity).|||Nucleus|||Polyubiquitinated at Lys-145 by the SCF(FBXL17) complex, leading to its subsequent degradation (PubMed:28883095). Ubiquitination is regulated by acetylation at Lys-228 and Lys-233 (PubMed:28883095). Polyubiquitinated by E3 ubiquitin-protein ligase TRIM48, leading to suppression of MAP3K5/ASK1 methylation and subsequent MAP3K5 activation (By similarity).|||cytosol|||nucleoplasm http://togogenome.org/gene/10090:Fam172a ^@ http://purl.uniprot.org/uniprot/Q3TNH5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM172 family.|||Cytoplasm|||Endoplasmic reticulum|||Homozygotes deficient mice die before postnatal day 25. Mice display retinal coloboma, cleft palate, and hypoplastic semicircular canals, retarded growth, genital anomalies and malformation of the heart and cranial nerves. Mice display a complex phenotype mimicking both the major and minor features of CHARGE syndrome (CHARGES).|||Interacts with AGO2 (PubMed:29311329). Found in a complex, composed of AGO2, CHD7 and FAM172A (PubMed:29311329).|||Nucleus|||Plays a role in the regulation of alternative splicing, by interacting with AGO2 and CHD7. Seems to be required for stabilizing protein-protein interactions at the chromatin-spliceosome interface (PubMed:29311329). May have hydrolase activity (PubMed:29311329).|||Widely expressed during development. http://togogenome.org/gene/10090:Eeig1 ^@ http://purl.uniprot.org/uniprot/A0A158RFU0|||http://purl.uniprot.org/uniprot/Q78T81 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EEIG family.|||Cytoplasm|||Expressed during TNFSF11/RANKL-induced differentiation of bone marrow-derived macrophages to osteoclasts.|||Induced by NFATC1 in bone marrow-derived macrophages (PubMed:23478294). Induced by TNFSF11/RANKL and TNF in bone marrow macrophages (PubMed:32741026).|||Key component of TNFSF11/RANKL- and TNF-induced osteoclastogenesis pathways, thereby mediates bone resorption in pathological bone loss conditions (PubMed:23478294, PubMed:32741026). Required for TNFSF11/RANKL-induced osteoclastogenesis via its interaction with TNFRSF11A/RANK, thereby facilitates the downsteam transcription of NFATC1 and activation of PLCG2 (PubMed:23478294). Facilitates recruitment of the transcriptional repressor PRDM1/BLIMP1 to the promoter of the anti-osteoclastogenesis gene IRF8, thereby resulting in transcription of osteoclast differentiation factors (PubMed:32741026). May play a role in estrogen action (By similarity).|||Membrane raft|||No effect on bone mass under homeostatic conditions, however reduces osteoclast number, amount of bone destruction, number of osteolytic cavities and abundance of serum Acp5/TRAP levels in a lipopolysaccharide-induced bone destruction model.|||Nucleus|||Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Interacts with PRDM1/BLIMP1; following TNFSF11/RANKL stimulation in bone marrow-derived macrophages, the interaction promotes the binding of PRDM1/BLIMP1 to the gene promoter of IRF8 (PubMed:32741026). Interacts (via N-terminus) with TNFRSF11A/RANK (via cytoplasmic domain); when in the presence of TNFSF11/RANKL (PubMed:23478294). http://togogenome.org/gene/10090:Or8c17 ^@ http://purl.uniprot.org/uniprot/L7N210 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sco1 ^@ http://purl.uniprot.org/uniprot/Q5SUC9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SCO1/2 family.|||Copper metallochaperone essential for the maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). Not required for the synthesis of MT-CO2/COX2 but plays a crucial role in stabilizing MT-CO2/COX2 during its subsequent maturation. Involved in transporting copper to the Cu(A) site on MT-CO2/COX2 (By similarity). Plays an important role in the regulation of copper homeostasis by controlling the abundance and cell membrane localization of copper transporter CTR1 (PubMed:25683716, PubMed:28973536).|||Heart-specific and striated muscle-specific knockout mice exhibit a lethal phenotype due to a combined COX and copper deficiency that results in a dilated cardiomyopathy. Cardiac copper deficiency is caused by the mislocalization of copper transporter CTR1 to the cytoplasm (PubMed:28973536). Liver-specific knockout mice exhibit a lethal phenotype associated with profound hepatic COX and copper deficiencies. Hepatic copper deficiency is due to reduced localization of CTR1 at the cell membrane and an enhanced proteasomal degradation of CTR1 (PubMed:25683716).|||Homodimer. Interacts with COA6. Found in a complex with TMEM177, COX20, COA6, MT-CO2/COX2, COX18 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20 in a MT-CO2/COX2- and COX18-dependent manner. Interacts with COX16.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Actmap ^@ http://purl.uniprot.org/uniprot/J3QPC3 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actin maturation protease that specifically mediates the cleavage of immature acetylated N-terminal actin, thereby contributing to actin maturation (PubMed:36173861). Cleaves N-terminal acetylated methionine of immature cytoplasmic beta- and gamma-actins Actb and Actg1 after translation (PubMed:36173861). Cleaves N-terminal acetylated cysteine of muscle alpha-actins Acta1, Actc1 and Acta2 after canonical removal of N-terminal methionine (PubMed:36173861).|||Animals are alive, but suffer from muscle weakness (PubMed:36173861). Absence of cytoplasmic actin processing in intestine and kidney (PubMed:36173861). Accumulation of immature alpha-skeletal muscle (Acta1), alpha-cardiac muscle (Actc1), and alpha-smooth muscle (Actc2) actin with N-terminal acetylated cysteine (PubMed:36173861). Undetectable actin maturation and accumulation of immature actin in acetylated and methionated state in intestine and kidney, however no effect on the total levels of actin (PubMed:36173861). Shorter sarcomeric thin filaments in skeletal muscle, decrease in muscle function and progressive accumulation of centralized nuclei, a common hallmark of myopathies (PubMed:36173861).|||Belongs to the ACTMAP family.|||Cytoplasm|||Interacts (via N-terminus) with PFN2 isoforms 1/IIa and 2/IIb; the interactions may facilitate efficient cleavage of the acetylated N-terminus of immature actin (By similarity). Interacts with PFN1 (By similarity).|||The N-terminal proline-rich disordered region contributes to the interaction with PFN2. http://togogenome.org/gene/10090:Rps13 ^@ http://purl.uniprot.org/uniprot/P62301|||http://purl.uniprot.org/uniprot/Q5BLJ7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS15 family.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Cytoplasm|||Ubiquitinated at Lys-27 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).|||nucleolus http://togogenome.org/gene/10090:Cep250 ^@ http://purl.uniprot.org/uniprot/Q60952 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ C-terminal part is phosphorylated by NEK2. Dephosphorylated in vitro by the PP1 phosphatase (By similarity).|||Expressed in the retina.|||May be involved in ciliogenesis. Probably plays an important role in centrosome cohesion during interphase.|||Monomer and homodimer (Probable). Forms a complex in vitro with both NEK2 kinase and the PPP1CC catalytic subunit of protein phosphatase 1 (PP1) (By similarity). Interacts with CEP135 (By similarity). Interacts with CROCC/rootletin (PubMed:16339073). Interacts with CNTLN (By similarity). Interacts with NIN (via C-terminus) (PubMed:27565344).|||Photoreceptor inner segment|||centriole|||cilium basal body|||perinuclear region|||photoreceptor outer segment http://togogenome.org/gene/10090:Abtb3 ^@ http://purl.uniprot.org/uniprot/Q6GQW0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Adam25 ^@ http://purl.uniprot.org/uniprot/A0A0R4J160|||http://purl.uniprot.org/uniprot/Q9R159 ^@ Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Adult levels are reached by day 25 after birth.|||Binds 1 zinc ion per subunit.|||Expressed specifically in testis.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Sperm surface membrane protein that may be involved in spermatogenesis and fertilization.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme. http://togogenome.org/gene/10090:Gata4 ^@ http://purl.uniprot.org/uniprot/E9PXW9|||http://purl.uniprot.org/uniprot/Q08369|||http://purl.uniprot.org/uniprot/Q3UYJ1 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By retinoic acid.|||Heart, intestine, liver, primative endoderm and gonads.|||Interacts with ZNF260 (By similarity). Interacts with the homeobox domain of NKX2-5 through its C-terminal zinc finger. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts (via the second Zn finger) with NFATC4 (PubMed:9568714). Interacts with LMCD1 (PubMed:16199866). Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes. Interacts with NR5A1, ZFPM2 and TBX5. Interacts with TBX18. Interacts with GLYR1; the interaction is required for a synergistic activation of GATA4 target genes transcription (By similarity).|||Methylation at Lys-299 attenuates transcriptional activity.|||Nucleus|||Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development (PubMed:35182466). In cooperation with TBX5, it binds to cardiac super-enhancers and promotes cardiomyocyte gene expression, while it down-regulates endocardial and endothelial gene expression (By similarity). Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression (By similarity). Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity). Acts as a transcriptional activator of ANF in cooperation with NKX2-5 (PubMed:9584153). Promotes cardiac myocyte enlargement (By similarity). Required during testicular development (By similarity). May play a role in sphingolipid signaling by regulating the expression of sphingosine-1-phosphate degrading enzyme, sphingosine-1-phosphate lyase (By similarity). http://togogenome.org/gene/10090:Gsx1 ^@ http://purl.uniprot.org/uniprot/B2RQ55|||http://purl.uniprot.org/uniprot/P31315 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Probable transcription factor that binds to the DNA sequence 5'-GC[TA][AC]ATTA[GA]-3'. Activates the transcription of the GHRH gene. Plays an important role in pituitary development. http://togogenome.org/gene/10090:Hnrnpab ^@ http://purl.uniprot.org/uniprot/Q20BD0|||http://purl.uniprot.org/uniprot/Q544Z3|||http://purl.uniprot.org/uniprot/Q99020 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with APOBEC1 (By similarity).|||Nucleus|||Transcriptional repressor. Binds to CArG box motifs, single-stranded and double-stranded DNA, and RNA. It may be that repression by CBF-A is a result of competitive binding of CBF, a putative positive factor, and CBF-A to the same or overlapping motifs around the CArG boxes.|||Ubiquitous. http://togogenome.org/gene/10090:Brpf3 ^@ http://purl.uniprot.org/uniprot/B2KF05 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of some HBO1 complexes composed of KAT7/HBO1, MEAF6, ING4 or ING5, and BRPF3. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with KAT7/HBO1; the interaction is direct.|||Highly expressed in the adult testis and brain.|||No visible phenotype.|||Nucleus|||Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity. Plays a role in DNA replication initiation by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby facilitating the activation of replication origins. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.|||Widely expressed in embryos at 12.5 dpc. http://togogenome.org/gene/10090:Spata19 ^@ http://purl.uniprot.org/uniprot/Q9DAQ9 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Essential for sperm motility and male fertility (PubMed:26265198). Plays an important role in sperm motility by regulating the organization and function of the mitochondria and is also required for correct sperm midpiece assembly (PubMed:26265198).|||Expressed specifically in adult testis (at protein level).|||Male mice are infertile, their sperms exhibit disorganized mitochondrial structure and the sperm-abundance of mitochondrial proteins and activities of mitochondrial respiratory chain complex IV, and ATP levels are significantly reduced (PubMed:26265198). Epididymal sperm possess seriously disrupted midpieces, leading to a severe reduction in sperm motility and infertility (PubMed:26265198).|||Mitochondrion|||Mitochondrion outer membrane|||flagellum http://togogenome.org/gene/10090:Itgax ^@ http://purl.uniprot.org/uniprot/Q9QXH4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. Alpha-X associates with beta-2 (By similarity).|||Integrin alpha-X/beta-2 is a receptor for fibrinogen. It recognizes the sequence G-P-R in fibrinogen. It mediates cell-cell interaction during inflammatory responses. It is especially important in monocyte adhesion and chemotaxis (By similarity).|||Membrane|||The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. http://togogenome.org/gene/10090:E2f7 ^@ http://purl.uniprot.org/uniprot/Q6S7F2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1. Acts as a regulator of S-phase by recognizing and binding the E2-related site 5'-TTCCCGCC-3' and mediating repression of G1/S-regulated genes. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Also involved in DNA damage response: up-regulated by p53/TP53 following genotoxic stress and acts as a downstream effector of p53/TP53-dependent repression by mediating repression of indirect p53/TP53 target genes involved in DNA replication. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. Acts as a negative regulator of keratinocyte differentiation.|||Belongs to the E2F/DP family.|||Highly expressed during mid to late S-phase.|||In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (PubMed:12893818).|||Induced at the onset of hepatocyte polyploidization.|||Interacts with HIF1A (By similarity). Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with E2F8. Dimerization is important for DNA-binding. Interacts with MN1 (By similarity).|||No visible phenotype; mice develop normally and live to old age. E2f7 and E2f8 double knockout embryos die by 11.5 dpc of massive apoptosis and dilation of blood vessels and show increased expression of E2f1 and Tp53, as well as many stress-related genes.|||Nucleus|||Widely expressed with highest levels in skin and thymus and very low levels in brain, muscle and stomach. Expressed in trophoblast giant cells throughout placenta development (at protein level). http://togogenome.org/gene/10090:Zfand2b ^@ http://purl.uniprot.org/uniprot/Q91X58 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 'Lys-48'-linked polyubiquitin chains of ubiquitinated proteins (PubMed:18467495, PubMed:24160817, PubMed:26876100). Associates with the proteasome complex; upon exposure to arsenite (PubMed:18467495, PubMed:26876100). Interacts (via VIM motif) with VCP; the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with BAG6 (PubMed:24160817, PubMed:26337389, PubMed:26876100). Interacts with IGF1R (nascent precursor form) (PubMed:26692333). Interacts with DERL1, FAF2, NPLOC4 and UFD1; probably through VCP (PubMed:24160817).|||Endoplasmic reticulum membrane|||Knockout mice undergo premature death due to the occurrence of myelo-proliferative neoplasms. The absence of Zfand2b plays a driver role in the development of these neoplasms by hyperactivating the insulin-like growth factor receptor signaling pathway. This is due to increased expression, in particular at the cell surface, of the IGF1R receptor.|||Phosphorylated by MAPK14 (Probable). Phosphorylation has no effect on association with the proteasome complex (Probable).|||Plays a role in protein homeostasis by regulating both the translocation and the ubiquitin-mediated proteasomal degradation of nascent proteins at the endoplasmic reticulum (PubMed:24160817, PubMed:26337389, PubMed:26692333). It is involved in the regulation of signal-mediated translocation of proteins into the endoplasmic reticulum (PubMed:24160817). It also plays a role in the ubiquitin-mediated proteasomal degradation of proteins for which signal-mediated translocation to the endoplasmic reticulum has failed (PubMed:18467495, PubMed:26337389). May therefore function in the endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:24160817, PubMed:26337389). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).|||The UIM domains specifically bind 'Lys-48'-linked ubiquitin polymers (PubMed:18467495, PubMed:26876100). The UIM domains mediate interaction with polyubiquitinated proteins (PubMed:18467495, PubMed:26337389). http://togogenome.org/gene/10090:Pla2g2f ^@ http://purl.uniprot.org/uniprot/Q9QZT4 ^@ Cofactor|||Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Cell membrane|||No signal peptide could be predicted in this isoform, challenging its subcellular location within the secretory pathway and hence the formation of disulfide bonds, which are required for its activity.|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids (PubMed:10531313). Hydrolyzes the ester bond of the fatty acyl group attached at the sn-2 position of phospholipids (phospholipase A2 activity), the catalytic efficiency decreasing in the following order: phosphatidylglycerols > phosphatidylethanolamines > phosphatidylcholines > phosphatidylserines (PubMed:11877435, PubMed:10531313). May play a role in lipid mediator production in inflammatory conditions, by providing arachidonic acid to downstream cyclooxygenases and lipoxygenases (PubMed:10531313).|||Strongly expressed during embryogenesis.|||Strongly expressed in testis.|||Strongly up-regulated by lipopolysaccharide (LPS) in brain, heart, liver, colon and testis. http://togogenome.org/gene/10090:Cdca5 ^@ http://purl.uniprot.org/uniprot/Q9CPY3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sororin family.|||Chromosome|||Cytoplasm|||Interacts with the APC/C complex (By similarity). Interacts with the chromatin-bound cohesin complex; the interaction is indirect, occurs after DNA replication and requires acetylation of the cohesin component SMC3. Interacts (via the FGF motif) with PDS5A and PDS5B; the interaction is direct and prevents the interaction of PDS5A with WAPL.|||Nucleus|||Phosphorylated. Phosphorylation, as cells enter mitosis, disrupts the interaction with PDS5A and relieves the inhibition of WAPL by CDCA5 (By similarity).|||Regulator of sister chromatid cohesion in mitosis stabilizing cohesin complex association with chromatin. May antagonize the action of WAPL which stimulates cohesin dissociation from chromatin. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Required for efficient DNA double-stranded break repair.|||The KEN box is required for the association with the APC/C complex.|||Ubiquitinated by the APC/C complex in G1, leading to its degradation. http://togogenome.org/gene/10090:Gdf5 ^@ http://purl.uniprot.org/uniprot/P43027|||http://purl.uniprot.org/uniprot/Q8BRW9 ^@ Disease Annotation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Cell membrane|||Defects in Gdf5 are the cause of brachypodism (bp) which alters the length and numbers of bones in the limbs but spares the axial skeleton.|||Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (By similarity). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (By similarity). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (PubMed:24076600). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (By similarity).|||Homodimer; disulfide-linked (By similarity). Interacts with serine proteases, HTRA1 and HTRA3 (PubMed:15206957, PubMed:14973287). Following LPS binding, may form a complex with CXCR4, HSP90AA1 and HSPA8 (By similarity). Interacts with high affinity with NOG; inhibits chondrogenesis (By similarity). Interacts with high affinity with BMPR1B and lower affinity with BMPR1A; positively regulates chondrocyte differentiation and induces SMAD-dependent signaling. Interacts with FBN1 (via N-terminal domain) and FBN2 (By similarity).|||Induced over 300-fold in tibialis anterior muscles 3 days following denervation. High expression is maintained at least until 10 days after denervation.|||Secreted http://togogenome.org/gene/10090:Izumo3 ^@ http://purl.uniprot.org/uniprot/A6PWV3 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Izumo family.|||Cell membrane|||Izumo is the name of a Japanese shrine to marriage.|||Monomer and homodimer.|||Sperm-specific (at protein level). http://togogenome.org/gene/10090:Prep ^@ http://purl.uniprot.org/uniprot/Q543B9|||http://purl.uniprot.org/uniprot/Q9QUR6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S9A family.|||Cleaves peptide bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long.|||Cytoplasm http://togogenome.org/gene/10090:Otulin ^@ http://purl.uniprot.org/uniprot/Q3UCV8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated.|||Belongs to the peptidase C65 family. Otulin subfamily.|||Cytoplasm|||Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:27523608, PubMed:29950720). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by regulating the activity of the LUBAC complex (By similarity). OTULIN function is mainly restricted to homeostasis of the LUBAC complex: acts by removing 'Met-1'-linked autoubiquitination of the LUBAC complex, thereby preventing inactivation of the LUBAC complex (PubMed:29950720). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608, PubMed:29950720). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a role in innate immune response by restricting linear polyubiquitin formation on LUBAC complex in response to NOD2 stimulation, probably to limit NOD2-dependent pro-inflammatory signaling (By similarity).|||Embryonic lethality (PubMed:23708998, PubMed:27523608). Specific deletion in immune cells leads to acute systemic inflammation characterized by rapid weight loss, increased levels of pro-inflammatory cytokines in serum, neutrophilia with all the hallmarks of emergency granulopoiesis (PubMed:27523608). Specific deletion in T- or B-cells generates healthy mice with no overt inflammatory phenotypes (PubMed:27523608). In contrast, specific deletion in myeloid cells results in a strong inflammatory phenotype, characterized by chronic inflammation and autoimmunity, caused by sterile autoactivation of inflammatory pathways (PubMed:27523608).|||Enriched in a subset of endothelial cells near presumptive tips of vessels and vascular buds (at protein level).|||Interacts (via the PUB domain) with RNF31 (via the PIM motif); the interaction is direct (PubMed:23708998). Interacts with DVL2 (PubMed:23708998).|||Phosphorylated. Phosphorylation at Tyr-56 prevents interaction with RNF31; dephosphorylation promotes interaction with RNF31 and the LUBAC complex.|||The PIM (PUB-interaction motif) motif mediates interaction with the PUB domain of RNF31. Does not interact with other PUB domain-containing proteins. Phosphorylation at Tyr-56 prevents interaction with RNF31.|||The specificity for linear polyubiquitin is given by the 'Glu-16' residue in ubiquitin chain.|||Ubiquitinated. http://togogenome.org/gene/10090:Mxra7 ^@ http://purl.uniprot.org/uniprot/Q9CZH7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cdh16 ^@ http://purl.uniprot.org/uniprot/O88338 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.|||Cell membrane|||Kidney specific.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Ccdc149 ^@ http://purl.uniprot.org/uniprot/F6V035 ^@ Similarity ^@ Belongs to the CCDC149 family. http://togogenome.org/gene/10090:Aplf ^@ http://purl.uniprot.org/uniprot/Q9D842 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APLF family.|||Chromosome|||Histone chaperone involved in single-strand and double-strand DNA break repair (By similarity). Recruited to sites of DNA damage through interaction with branched poly-ADP-ribose chains, a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions (By similarity). Following recruitment to DNA damage sites, acts as a histone chaperone that mediates histone eviction during DNA repair and promotes recruitment of histone variant MACROH2A1 (PubMed:27875275). Also has a nuclease activity: displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro (By similarity). Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage (By similarity). Together with PARP3, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). Also acts as a negative regulator of cell pluripotency by promoting histone exchange (PubMed:27875275). Required for the embryo implantation during the epithelial to mesenchymal transition in females (PubMed:33277378).|||Interacts with LIG4 (By similarity). Interacts with PARP1 (By similarity). Interacts with XRCC4. Interacts (via KBM motif) with XRCC5 and XRCC6; promoting recruitment to DNA damage sites (By similarity). Interacts with XRCC1 (By similarity). Interacts (via C-terminal disordered region) with histones; interacts with histone H2A, H2B and H3-H4 (By similarity).|||Nucleus|||Phosphorylated in an ATM-dependent manner upon double-strand DNA break.|||Poly-ADP-ribosylated. In addition to binding non covalently poly-ADP-ribose via its PBZ-type zinc fingers, the protein is also covalently poly-ADP-ribosylated by PARP1.|||Present in the 4-cell stage (PubMed:33277378). Expression is enhanced in early morula and late morula stage embryos (PubMed:33277378). Down-regulated during the first differentiation to form inner cell mass and trophectoderm within a blastocyst (32-cell stage) (PubMed:33277378).|||The FHA-like domain mediates interaction with XRCC1 and XRCC4.|||The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites.|||The NAP1L motif is required for the histone chaperone activity.|||The PBZ-type zinc fingers (also named CYR) mediate non-covalent poly-ADP-ribose-binding. Specifically recognizes branched poly-ADP-ribose chains generated by PARP2. Poly-ADP-ribose-binding is dependent on the presence of zinc and promotes its recruitment to DNA damage sites.|||cytosol http://togogenome.org/gene/10090:Cxadr ^@ http://purl.uniprot.org/uniprot/P97792 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Cell membrane|||Component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. Also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. Upon epithelial CXADR-binding, JAML induces downstream cell signaling events in gamma-delta T-cells through PI3-kinase and MAP kinases. It results in proliferation and production of cytokines and growth factors by T-cells that in turn stimulate epithelial tissues repair.|||Expressed in liver, kidney, heart, lung, and brain. In skeletal muscle is found at the neuromuscular junction. In cardiac muscle, isoform 1 and isoform 2 are found at intercalated disks.|||Expression starts in the embryonic ectoderm in the uterus on 6.5 dpc. Then it is strongly expressed in the neuroepithelium of the neural tube, the developing brain and the spinal cord from 8.5 dpc to postnatal day 7 (P7), in the cranial motor nerves from 9.5 dpc to 11.5 dpc, and in the optic nerve from 13.5 dpc to P7. Expression increases until perinatal period and decreases postnatally. Expressed in the immature neuroepithelium including progenitor cells it still occurs in a few proliferating cells of the hippocampal dentate gyrus, the subventricular zone of the lateral ventricles, and the rostral migratory stream over P21. Also expressed in heart, kidney and liver of newborn mice.|||Monomer. May form homodimer. Interacts with LNX, MAGI1, DLG4, PRKCABP, TJP1 and CTNNB1. Interacts with MPDZ; recruits MPDZ to intercellular contact sites. Interacts with JAML (homodimeric form).|||Palmitoylated on Cys-259 and/or Cys-260; required for proper localization to the plasma membrane.|||Secreted|||The Ig-like C2-type 1 domain mediates homodimerization and interaction with JAML.|||The PDZ-binding motif mediates interaction with MPDZ and MAGI1.|||adherens junction|||tight junction http://togogenome.org/gene/10090:Gm13289 ^@ http://purl.uniprot.org/uniprot/Q8CD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Tmtc1 ^@ http://purl.uniprot.org/uniprot/Q3UV71 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMTC family.|||Endoplasmic reticulum|||May interact with FAM168B.|||Membrane|||Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3. http://togogenome.org/gene/10090:Pex10 ^@ http://purl.uniprot.org/uniprot/B1AUE5 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pex2/pex10/pex12 family.|||Component of the PEX2-PEX10-PEX12 retrotranslocation channel, composed of PEX2, PEX10 and PEX12. Interacts with PEX19.|||E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (By similarity). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX10 also regulates PEX5 recycling by acting as a E3 ubiquitin-protein ligase (By similarity). When PEX5 recycling is compromised, PEX10 catalyzes polyubiquitination of PEX5 during its passage through the retrotranslocation channel, leading to its degradation (By similarity).|||Peroxisome membrane|||The E3 ubiquitin-protein ligase activity is stimulated by PEX12.|||The three subunits of the retrotranslocation channel (PEX2, PEX10 and PEX12) coassemble in the membrane into a channel with an open 10 Angstrom pore. The RING-type zinc-fingers that catalyze PEX5 receptor ubiquitination are positioned above the pore on the cytosolic side of the complex. http://togogenome.org/gene/10090:Piwil1 ^@ http://purl.uniprot.org/uniprot/Q9JMB7 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arginine methylation by PRMT5 is required for the interaction with Tudor domain-containing protein (TDRD1, TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9) and subsequent localization to the meiotic nuage, also named P granule.|||Belongs to the argonaute family. Piwi subfamily.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Endoribonuclease that plays a central role in postnatal germ cells by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:11578866, PubMed:22121019, PubMed:21237665). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:11578866, PubMed:22121019, PubMed:21237665). Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:11578866, PubMed:22121019, PubMed:21237665). Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias) (PubMed:24757166). Not involved in the piRNA amplification loop, also named ping-pong amplification cycle (PubMed:22121019). Acts as an endoribonuclease that cleaves transposon messenger RNAs (PubMed:22121019). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation (PubMed:16938833). Probable component of some RISC complex, which mediates RNA cleavage and translational silencing (PubMed:16938833). Also plays a role in the formation of chromatoid bodies and is required for some miRNAs stability (PubMed:16787948). Required to sequester RNF8 in the cytoplasm until late spermatogenesis; RNF8 being released upon ubiquitination and degradation of PIWIL1 (PubMed:28552346).|||Expressed in brain. Expressed in testis, specifically in spermatocytes (at protein level). Only detected in germ lineage cells of adult testis. Expressed in male gonads 2 weeks after birth at the initiation of spermatogenesis, but not expressed in female gonads.|||Expression is activated by MYBL1/A-MYB.|||Interacts (via Piwi domain) with DICER1, suggesting that it forms ribonucleoprotein RISC complexes; this interaction is regulated by HSP90AB1 activity (PubMed:16938833). Interacts with MAEL, KIF17, PABPC1, PRMT5 and WDR77 (PubMed:16787948, PubMed:16787967, PubMed:19020299, PubMed:19584108). Interacts (when methylated on arginine residues) with TDRD1, TDRKH/TDRD2, RNF17/TDRD4, TDRD6, TDRD7 and TDRD9 (PubMed:19584108, PubMed:19918066, PubMed:19926723, PubMed:23714778). Interacts with CLOCK (PubMed:22900038). Interacts with MOV10L1 (PubMed:20534472). Interacts with ANAPC10; interaction oly takes place following piRNA-binding (PubMed:23328397). Interacts with RNF8; leading to sequester RNF8 in the cytoplasm (PubMed:28552346). Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886).|||Mice display spermatogenic arrest at the beginning of the round spermatid stage, resembling the phenotype of CREM, a master regulator of spermiogenesis; mRNAs of FHL5/activator of CREM and CREM target genes are down-regulated in testes. Female are fertile but male are completely sterile, no sperm is found in the epididimus. Chromatoid bodies from round spermatids are not fully compacted and remain as a diffuse chromatoid material.|||The D-box (destruction box) acts as a recognition signal for association with the APC/C complex, ubiquitination and degradation (PubMed:23328397).|||The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs (PubMed:21237665). The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias) (PubMed:24757166).|||Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) in late spermatids, leading to its degradation (PubMed:23328397). Ubiquitination only takes place following piRNA-binding in adult testis (PubMed:23328397). Ubiquitination and degradation in late spermatogenesis by APC/C is probably required to release RNF8 from the cytoplasm and promote histone to protamine exchange by RNF8 (PubMed:28552346). http://togogenome.org/gene/10090:Fkbp7 ^@ http://purl.uniprot.org/uniprot/O54998 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds calcium.|||Endoplasmic reticulum lumen|||Expressed at highest levels in heart, lung and testis. Weakly expressed in kidney and lymph node. Little or no expression detected in brain, thymus, spleen and liver.|||Expression begins at embryonic day 8.5.|||Glycosylated.|||PPIases accelerate the folding of proteins during protein synthesis. http://togogenome.org/gene/10090:Zfand6 ^@ http://purl.uniprot.org/uniprot/Q9DCH6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with PKN1. Interacts with TRAF2 (By similarity). Interacts with mono- and polyubiquitin. Interacts with PEX6. Interacts with PEX5 (Cys-linked ubiquitinated).|||Involved in regulation of TNF-alpha induced NF-kappa-B activation and apoptosis. Involved in modulation of 'Lys-48'-linked polyubiquitination status of TRAF2 and decreases association of TRAF2 with RIPK1 (By similarity). Required for PTS1 target sequence-dependent protein import into peroxisomes and PEX5 stability; may cooperate with PEX6. In vitro involved in PEX5 export from the cytosol to peroxisomes.|||The A20-type zinc finger domain mediates regulation of NF-kappa-B activity.|||The AN1-type zinc finger domain mediates association with TRAF2. http://togogenome.org/gene/10090:Entrep3 ^@ http://purl.uniprot.org/uniprot/E9Q6C9|||http://purl.uniprot.org/uniprot/Q5HZJ5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ENTREP family.|||May interact with WWOX.|||Membrane http://togogenome.org/gene/10090:Cyp2d40 ^@ http://purl.uniprot.org/uniprot/Q6P8N9 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Arid1a ^@ http://purl.uniprot.org/uniprot/A2BH40 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of SWI/SNF chromatin remodeling complexes, in some of which it can be mutually exclusive with ARID1B/BAF250B. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF (SWI/SNF-A) complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Component of a SWI/SNF-like EBAFa complex, at least composed of SMARCA4/BRG1/BAF190A, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCC1/BAF155, SMARCC2/BAF170, BAF250A and MLLT1/ENL. Interacts through its C-terminus with SMARCA2/BRM/BAF190B and SMARCA4/BRG1/BAF190A. Interacts with SMARCC1/BAF155 (By similarity). Interacts with FOS (via bZIP domain and leucine-zipper region), FOSB isoform 1 and 2, FOSL1 and FOSL2 (PubMed:29272704).|||Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5 dpc-16.5 dpc. In the earlier stages at 9.5 dpc and 10.5 dpc, is fairly ubiquitous though with clearly elevated expression in the progress zone and lateral mesoderm of limb buds, optic and otic vesicle, neural tube, and brain. Later on at 11.5 dpc and 12.5 dpc, expression becomes more restricted and is confined to the interdigital area of limbs, dorsal mes/metencephalon, neocortex, and neural tube. Expression is seen in the eye lens from 10.5 dpc until 12.5 dpc.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (PubMed:17640523).|||Nucleus|||Widely expressed. Expressed at high levels in the testis. http://togogenome.org/gene/10090:Gle1 ^@ http://purl.uniprot.org/uniprot/Q8R322 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with the NPC, however it may not be a stable component of the NPC complex since it shuttles between the nucleus and the cytoplasm. Interacts with nuclear pore complex proteins NUP155 and NUPL2 (By similarity).|||Belongs to the GLE1 family.|||Cytoplasm|||Nucleus|||Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm. May be involved in the terminal step of the mRNA transport through the nuclear pore complex (NPC) (By similarity).|||nuclear pore complex http://togogenome.org/gene/10090:Abcb1b ^@ http://purl.uniprot.org/uniprot/B2RUR3|||http://purl.uniprot.org/uniprot/P06795 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.|||Cell membrane|||Cytoplasm|||In mouse the MDR gene family includes three or more related but distinct cellular genes.|||Interacts with PSMB5.|||Membrane|||Several phosphorylated serine residues are present in the linker domain.|||Translocase activity is inhibited by verapamil and is sensitive to energy depletion. C1orf115 regulates drug efflux through modulation of ABCB1 localization and activity.|||Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins. Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. http://togogenome.org/gene/10090:Cth ^@ http://purl.uniprot.org/uniprot/Q8VCN5 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by calmodulin in the presence of calcium ions.|||Belongs to the trans-sulfuration enzymes family.|||Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate. Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione. Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce hydrogen sulfide (H2S). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, and two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia. Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (By similarity). Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function (PubMed:19903941, PubMed:22244329). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (PubMed:18948540) (By similarity). Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (PubMed:33826201). Can also accept homoserine as substrate (By similarity). Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity).|||Cytoplasm|||Detected in liver and kidney, and at lower levels in small intestine (at protein level) (PubMed:15038791). Highly expressed in liver, kidney and lung, detected at lower levels in stomach, small intestine and adipose tissue, and hardly found in heart, bone, and thymus (PubMed:15038791, PubMed:20305127).|||First detected at low levels in embryonic liver after 12.5 days of embryonic development. Highly expressed in liver and kidney after 18.5 days of embryonic development. Expressed at high levels in liver and kidney after birth and in adults. Age-dependent expression in mouse skeletal muscles; protein expression in skeletal muscles increased 5 days after birth, and remained stable until 10 weeks, then slightly decreased at 26 weeks and was significantly lower at 51 weeks (PubMed:33826201).|||Homotetramer (By similarity). Interacts with CALM in a calcium-dependent manner (PubMed:18948540).|||No visible phenotype at birth. Mice exhibit strongly decreased levels of hydrogen sulfide (H2S) in heart and aorta. Mice also show absence of protein sulfhydration on target proteins. Hydrogen sulfide serum levels are also lower than normal. No effect on brain hydrogen sulfide levels. Age-dependent hypertension beginning at about seven weeks of age (PubMed:18948540, PubMed:19903941). Deteriorated the loss of skeletal muscle mass in aging mice (PubMed:33826201).|||Tumor necrosis factor alpha (TNF-alpha) promotes the binding of SP1 to the CSE promoter, inducing its transcription. http://togogenome.org/gene/10090:Pnma5 ^@ http://purl.uniprot.org/uniprot/Q5DTT8 ^@ Similarity|||Tissue Specificity ^@ Belongs to the PNMA family.|||Restricted to testis, where expression is low. Not detected in the brain. http://togogenome.org/gene/10090:Ptk7 ^@ http://purl.uniprot.org/uniprot/Q8BKG3 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell junction|||Expressed at high levels in lung and un-pregnant uterus among adult tissues, and in the tail, limbs, somites, gut and craniofacial regions among embryonic tissues.|||Inactive tyrosine kinase involved in Wnt signaling pathway. Component of both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathway. Functions in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization and apoptosis. Has a role in embryogenesis, epithelial tissue organization and angiogenesis.|||Interacts with CTNNB1.|||MMP14 cleaves PTK7 between Pro-613 and Leu-614 generating an N-terminal soluble (70 kDa) fragment and a membrane C-terminal (50 kDa) fragment. Proteolysis by MMP14 regulates PTK7 function in non-canonical Wnt signaling pathway.|||Membrane|||Mice die perinatally and display craniorachischisis, a severe form of neural tube defect in which the neural tube fails to close from the midbrain hindbrain boundary to the base of the spine. Chuzhoi mutants also display disruption of planar cell polarity in the inner ear, and defective heart and lung development.|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Or4c102 ^@ http://purl.uniprot.org/uniprot/A2AV11 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Filip1 ^@ http://purl.uniprot.org/uniprot/Q9CS72 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FILIP1 family.|||By acting through a filamin-A/F-actin axis, it controls the start of neocortical cell migration from the ventricular zone. May be able to induce the degradation of filamin-A.|||Interacts with FLNA. Interacts with RHOD (in GTP-bound form).|||cytoskeleton http://togogenome.org/gene/10090:Tns3 ^@ http://purl.uniprot.org/uniprot/A0A5F8MP98|||http://purl.uniprot.org/uniprot/Q5SSZ5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PTEN phosphatase protein family.|||Expressed at 13.5 dpc in lung, liver, spleen, stomach, aorta, trachea, and perichondrium (PubMed:15733665). Expression increases during osteoclast differentiation (PubMed:27505886).|||Expressed in brain, heart, lung, liver, spleen, kidney, stomach, small intestine, skeletal muscle, skin, thymus, testis, uterus, placenta, aorta and trachea.|||Interacts with EGFR; EGF promotes the interaction with EGFR (By similarity). Interacts with PTK2/FAK1 and BCAR1 (By similarity). Tyrosine phosphorylation is critical for these interactions (By similarity). Interacts with Rho GTPase-activating protein DLC1 and with the regulatory p85 subunit of the PI3K kinase complex; in resting cells, interacts (via C2 tensin-type domain) with DLC1 but, following growth factor stimulation, TNS3 is phosphorylated which leads to weakened interaction with DLC1 and enhanced interaction (via C2 tensin-type domain) with p85 while DLC1 interaction with PTEN increases (By similarity). Interacts (when phosphorylated on the SH2 domain) with integrins ITGB1, ITGB3 and ITGB5 and with scaffolding protein PEAK1 (phosphorylated on 'Tyr-632'); these interactions mediate the association of PEAK1 with ITGB1, ITGB3 and ITGB5 (PubMed:35687021). Interacts (via N-terminus) with DOCK5 (via N-terminus); the interaction increases DOCK5 guanine nucleotide exchange activity towards Rac (PubMed:27505886). Interacts with receptor tyrosine kinase MET (By similarity).|||May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in the dissociation of the integrin-tensin-actin complex (By similarity). EGF activates TNS4 and down-regulates TNS3 which results in capping the tail of ITGB1 (By similarity). Increases DOCK5 guanine nucleotide exchange activity towards Rac and plays a role in osteoclast podosome organization (PubMed:27505886). Enhances RHOA activation in the presence of DLC1 (By similarity). Required for growth factor-induced epithelial cell migration; growth factor stimulation induces TNS3 phosphorylation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex, displacing PI3K inhibitor PTEN and resulting in translocation of the TNS3-p85 complex to the leading edge of migrating cells to promote RAC1 activation (By similarity). Meanwhile, PTEN switches binding preference from p85 to DLC1 and the PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA (By similarity). Acts as an adapter protein by bridging the association of scaffolding protein PEAK1 with integrins ITGB1, ITGB3 and ITGB5 which contributes to the promotion of cell migration (PubMed:35687021). Controls tonsil-derived mesenchymal stem cell proliferation and differentiation by regulating the activity of integrin ITGB1 (By similarity).|||Mice display growth retardation and incomplete development of small intestine, lung, and bone. Postnatal lethality is detected in one third of the homozygous mutants.|||Phosphorylated on Ser/Thr and Tyr residues. Phosphorylated on Thr-323 in the C2-type tensin domain following EGF stimulation which changes its binding preference from DLC1 to the p85 regulatory subunit of the PI3K kinase complex. EGF induces tyrosine phosphorylation in a time- and dose-dependent manner. Phosphorylation of the SH2 domain enhances interaction with PEAK1.|||focal adhesion|||podosome http://togogenome.org/gene/10090:Gjc1 ^@ http://purl.uniprot.org/uniprot/A0A654IER4|||http://purl.uniprot.org/uniprot/P28229 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins. Interacts with CNST.|||Belongs to the connexin family. Gamma-type subfamily.|||Cell membrane|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Mup22 ^@ http://purl.uniprot.org/uniprot/Q4FZE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Ugt2b34 ^@ http://purl.uniprot.org/uniprot/Q8K154 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Ccne2 ^@ http://purl.uniprot.org/uniprot/A2API1|||http://purl.uniprot.org/uniprot/Q544H6|||http://purl.uniprot.org/uniprot/Q9Z238 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin E subfamily.|||Essential for the control of the cell cycle at the late G1 and early S phase.|||Highest levels in adult testis, thymus and brain. Lower levels in placenta, spleen and colon.|||Interacts with the CDK2 (in vivo) and CDK3 (in vitro) protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex (By similarity).|||Nucleus|||Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway. http://togogenome.org/gene/10090:Prkab1 ^@ http://purl.uniprot.org/uniprot/Q542K0|||http://purl.uniprot.org/uniprot/Q9R078 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity).|||Belongs to the 5'-AMP-activated protein kinase beta subunit family.|||Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3) (By similarity).|||Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).|||Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.|||The glycogen-binding domain may target AMPK to glycogen so that other factors like glycogen-bound debranching enzyme or protein phosphatases can directly affect AMPK activity. http://togogenome.org/gene/10090:Sult1d1 ^@ http://purl.uniprot.org/uniprot/Q3UZZ6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Cytoplasm|||Detected in kidney and liver. Detected in kidney collecting duct cells.|||Sulfotransferase with broad substrate specificity that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, such as dopamine, prostaglandins, leukotriene E4, drugs and xenobiotic compounds. Has sulfotransferase activity towards p-nitrophenol, 2-naphthylamine and minoxidil (in vitro). Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites.|||Up-regulated in liver and kidney by dexamethasone, a glucocorticoid analog. http://togogenome.org/gene/10090:Gosr2 ^@ http://purl.uniprot.org/uniprot/O35166 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GOSR2 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.|||Part of a unique SNARE complex composed of the Golgi SNAREs GOSR1, STX5 and YKT6.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Ncbp1 ^@ http://purl.uniprot.org/uniprot/Q3UYV9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NCBP1 family.|||Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus via its interaction with ALYREF/THOC4/ALY, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC) via its interaction with UPF1, promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export and is particularly important in cellular stress situations such as virus infections. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export. NCBP1/CBP80 is required for cell growth and viability (By similarity).|||Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA. Found in a U snRNA export complex containing PHAX/RNUXA, NCBP1/CBP80, NCBP2/CBP20, RAN, XPO1 and m7G-capped RNA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with PHAX/RNUXA, SRRT/ARS2, EIF4G2, IGF2BP1, HNRNPF, HNRNPH1, KIAA0427/CTIF, PARN, DROSHA, UPF1 and ALYREF/THOC4. May interact with EIF4G1; the interaction is however controversial. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1/CBP80 and POLR2A (active). Component of an alternative nuclear cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3 (By similarity). Interacts with METTL3 (By similarity). Interacts with ZFC3H1 in a RNase-insensitive manner (By similarity). Interacts with MTREX (By similarity). Interacts with TASOR (PubMed:31112734). Interacts with DHX34; the interaction is RNA-dependent (By similarity). Interacts with KPNA3 (By similarity).|||Cytoplasm|||Expressed in the spermatogonia, spermatocytes and granular cells within the cerebellum.|||Nucleus http://togogenome.org/gene/10090:Defb19 ^@ http://purl.uniprot.org/uniprot/Q8K3I8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Not detected at 11.5 dpc. Specific signals are observed within seminiferous cords in male gonads at 12.5, 13.5, 14.5, and 16.5 dpc and in newborn testes. In 16.5 and newborn testes, its expression is also found in epididymis. No specific signal is found in female gonads.|||Secreted|||Specifically expressed in male gonads (Sertoli cells). http://togogenome.org/gene/10090:Wdr45 ^@ http://purl.uniprot.org/uniprot/Q91VM3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat PROPPIN family.|||Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Binds phosphatidylinositol 3-phosphate (PtdIns3P). Activated by the STK11/AMPK signaling pathway upon starvation, WDR45 is involved in autophagosome assembly downstream of WIPI2, regulating the size of forming autophagosomes. Together with WIPI1, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes. Probably recruited to membranes through its PtdIns3P activity.|||Cytoplasm|||Interacts with WIPI1. Interacts with WIPI2. Interacts with ATG2A and ATG2B. Interacts with ULK1. May interact with the PRKAA1, PRKAA2, PRKAB1 and PRKAG1 subunits of the AMPK kinase. May interact with NUDC.|||Preautophagosomal structure|||The L/FRRG motif is required for recruitment to PtdIns3P. http://togogenome.org/gene/10090:Me2 ^@ http://purl.uniprot.org/uniprot/Q99KE1 ^@ Activity Regulation|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the malic enzymes family.|||Divalent metal cations. Prefers magnesium or manganese.|||Homotetramer.|||Mitochondrion matrix|||NAD-dependent mitochondrial malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate.|||Subject to allosteric activation by fumarate.|||This isoenzyme can also use NADP(+) but is more effective with NAD(+). http://togogenome.org/gene/10090:Prrx1 ^@ http://purl.uniprot.org/uniprot/G3UZ44|||http://purl.uniprot.org/uniprot/P63013 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer.|||Belongs to the paired homeobox family.|||Expressed during cardiogenesis.|||Expressed exclusively in mesodermally derived cell types. During embryogenesis, highest levels of expression are found in the mesenchyme and precartilage elements of the face and hind limbs. In the adult, expression is restricted to skeletal muscle, heart and uterus.|||Nucleus http://togogenome.org/gene/10090:Dcbld2 ^@ http://purl.uniprot.org/uniprot/Q91ZV3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Gtpbp1 ^@ http://purl.uniprot.org/uniprot/O08582 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. GTPBP1 subfamily.|||Cytoplasm|||Detected in some neurons in the brain cortex. Detected in small arteries, dendritic cells and macrophages in the thymus. Detected in lung bronchi, in bronchial epithelial cells and in bronchial smooth muscle cells. Detected in smooth muscle cells in a broad range of organs (at protein level). Expressed in brain, thymus, lung, and kidney.|||Interacts with EXOSC2/RRP4, EXOSC3/RRP40, EXOSC5/RRP46, HNRNPD, HNRNPR and SYNCRIP. Identified in a complex with AANAT mRNA, but does not bind mRNA by itself (By similarity).|||No visible phenotype. Mice are born at the expected Mendelian ratio, develop normally and are fertile. They exhibit increased stability of some mRNA species.|||Promotes degradation of target mRNA species. Plays a role in the regulation of circadian mRNA stability. Binds GTP and has GTPase activity (By similarity). http://togogenome.org/gene/10090:Or8g51 ^@ http://purl.uniprot.org/uniprot/Q8VF78 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbmy ^@ http://purl.uniprot.org/uniprot/O35698 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with splicing factor proteins SFRS3/SRP20, TRA2B/SFRS10, KHDRBS1/SAM68 and KHDRBS3.|||Nucleus|||Only expressed in spermatogonia and early spermatocytes, suggesting that expression is inactivated in the XY body during meiosis.|||Overexpression of Rbmy proteins in mice carrying the Y(d1) deletion that removes most of the multi-copy Rbmy gene cluster does not have any effect and fails to reduce the frequency of abnormal sperm. These results raize the question of the role of Rbmy proteins in sperm development.|||RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs.|||Testis-specific.|||The RBMY1 proteins are encoded by repeated regions of the Y chromosome. The exact number of functional copies is unclear and may vary between individuals, and some of them may represent pseudogenes. http://togogenome.org/gene/10090:Adamts17 ^@ http://purl.uniprot.org/uniprot/E9Q4D1|||http://purl.uniprot.org/uniprot/Q3V310 ^@ Caution|||Cofactor|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular matrix http://togogenome.org/gene/10090:Caap1 ^@ http://purl.uniprot.org/uniprot/Q8VDY9 ^@ Function ^@ Anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop. http://togogenome.org/gene/10090:Kcnq4 ^@ http://purl.uniprot.org/uniprot/Q9JK97 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basal cell membrane|||Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.4/KCNQ4 sub-subfamily.|||Homotetramer. May form heteromultimers with KCNQ3 (By similarity). Interacts with HSP90AB1; promotes cell surface expression of KCNQ4 (By similarity).|||In the inner ear expressed in the outer sensory hair cells of the cochlea and in type I hair cells of the vestibular organs. Also expressed in the postsynaptic membrane of the calyx nerve endings innervating type I cells. In the brain expressed in neurons of many, but not all, nuclei of the central auditory pathway. Absent from most other brain regions.|||Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea.|||The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded (By similarity).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Gm14744 ^@ http://purl.uniprot.org/uniprot/B1AVU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Cavin1 ^@ http://purl.uniprot.org/uniprot/O54724 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAVIN family.|||Cell membrane|||Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4 (PubMed:19546242). Homotrimer (PubMed:25588833). Interacts with LIPE in the adipocyte cytoplasm (By similarity). Interacts with RNA polymerase I (PubMed:9582279). Interacts with TTF1 (PubMed:9582279, PubMed:27528195). Binds the 3' end of pre-rRNA (PubMed:9582279). Interacts with transcription factor ZNF148 (PubMed:10727401). Interacts with CAV1, CAVIN2 and CAVIN3 (PubMed:25588833, PubMed:19546242). Interacts with CAVIN4 (PubMed:19546242).|||Endoplasmic reticulum|||Expressed in the heart, stomach, adipose tissue and lung (at protein level). Expressed in testis, kidney, muscle, liver, spleen and brain.|||Mice show a metabolic phenotype of significantly reduced adipose tissue mass, higher circulating triglyceride levels, glucose intolerance, and hyperinsulinemia, consistent with a lipodystrophy. Cells from various tissues, including lung epithelium, intestinal smooth muscle, skeletal muscle, and endothelial cells showed no detectable caveolae cells.|||Microsome|||Mitochondrion|||Monoubiquitinated.|||Nucleus|||Phosphorylated. Present in active and inactive forms. Changes in phosphorylation pattern may alter activity. Phosphorylation at Tyr-158 is essential for its function in the regulation of the ribosomal transcriptional activity.|||Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues (PubMed:18191225, PubMed:18840361, PubMed:18056712, PubMed:30188967). Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1) (PubMed:19546242). Essential for normal oligomerization of CAV1 (PubMed:23652019). Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop (PubMed:27528195). Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template (PubMed:9582279, PubMed:11139612). The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A (PubMed:30188967).|||The leucine-zipper domain 1 is essential for its localization in the caveolae.|||caveola|||cytosol http://togogenome.org/gene/10090:Or2h2 ^@ http://purl.uniprot.org/uniprot/Q0VEL5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bbx ^@ http://purl.uniprot.org/uniprot/Q8VBW5 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Contaminating sequence. Potential poly-A sequence.|||Nucleus|||Transcription factor that is necessary for cell cycle progression from G1 to S phase. http://togogenome.org/gene/10090:Hbq1a ^@ http://purl.uniprot.org/uniprot/Q8BYM1 ^@ Similarity ^@ Belongs to the globin family. http://togogenome.org/gene/10090:Chmp4b ^@ http://purl.uniprot.org/uniprot/Q9D8B3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||ISGylated. Isgylation weakens its interaction with VPS4A (By similarity).|||Late endosome membrane|||Midbody|||Nucleus envelope|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan.|||Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with CHMP6 and CHMP4C. Interacts with PDCD6IP; the interaction is direct. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with CHMP7. Interacts with CFTR; the interaction requires misfolded CFTR. Interacts with PTPN23 (By similarity).|||The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components (By similarity).|||cytosol http://togogenome.org/gene/10090:Mup7 ^@ http://purl.uniprot.org/uniprot/Q58EV3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Stxbp2 ^@ http://purl.uniprot.org/uniprot/Q548T0|||http://purl.uniprot.org/uniprot/Q64324 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Expressed in testis, intestine, kidney, rat adipose tissue and 3T3-L1 cells.|||Interacts with STX1A, STX2 and STX3. Interacts with STX11.|||Involved in intracellular vesicle trafficking and vesicle fusion with membranes. Contributes to the granule exocytosis machinery through interaction with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that regulate membrane fusion. Regulates cytotoxic granule exocytosis in natural killer (NK) cells (By similarity). http://togogenome.org/gene/10090:Or8w1 ^@ http://purl.uniprot.org/uniprot/Q8VG97 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Traf3ip1 ^@ http://purl.uniprot.org/uniprot/Q149C2 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAF3IP1 family.|||Contaminating sequence. Potential poly-A sequence.|||Homozygous mutant mice are not viable and have neural development defects, abnormal neural tube patterning, polydactyly, cardiac edema, and variable microphthalmia. Mutant cells have a marked reduction in the number of cilia.|||Interacts with IL13RA1. Binds to microtubules, TRAF3 and DISC1 (By similarity). Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88. Interacts with IFT88. Interacts with MAP4 (PubMed:26487268).|||Plays an inhibitory role on IL13 signaling by binding to IL13RA1. Involved in suppression of IL13-induced STAT6 phosphorylation, transcriptional activity and DNA-binding. Recruits TRAF3 and DISC1 to the microtubules (By similarity). Involved in epithelial morphogenesis and in the regulation of microtubule cytoskeleton organization. Is a negative regulator of microtubule stability, acting through the control of MAP4 levels (PubMed:26487268). Involved in ciliogenesis (PubMed:21945076).|||cilium|||cilium axoneme|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:St3gal5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1J3|||http://purl.uniprot.org/uniprot/O88829 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ (Microbial infection) Cerebellar granule cells are no longer susceptible to C.botulinum neurotoxin type C (BoNT/C), and syntaxin, the BoNT/C target, is not degraded. Cells remain susceptible to neurotoxins C.botulinum neurotoxin types CD and D (BoNT/CD and BoNT/D, botD) (PubMed:16115873). Knockout mice survive 6 times longer when injected intravenously with BoNT/C; the knockout has no effects on time of survival for BoNT/CD and BoNT/D (PubMed:16115873).|||(Microbial infection) Gangliosides GD1b and GT1b (derived from GM3) may serve as receptors for some C.botulinum neurotoxins (minimally types BoNT/A, B, C) (PubMed:16115873).|||Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||Mainly expressed in brain, and then testis, heart and liver, almost all tissues showed some levels of the gene expression.|||Membrane|||Mice are viable and fertile, and do not show any obvious abnormality apart from an increased sensitivity to insulin (PubMed:12629211). The major brain gangliosides derived from GM3 (GM1a, GD1a, GD1b, and GT1b) are missing (PubMed:12629211).|||Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the non-reducing terminal galactose (Gal) of glycosphingolipids forming gangliosides (important molecules involved in the regulation of multiple cellular processes, including cell proliferation and differentiation, apoptosis, embryogenesis, development, and oncogenesis) (PubMed:9875239, PubMed:10092602, PubMed:12629211). Mainly involved in the biosynthesis of ganglioside GM3 but can also use different glycolipids as substrate acceptors such as D-galactosylceramide (GalCer), asialo-GM2 (GA2) and asialo-GM1 (GA1), although less preferentially than beta-D-Gal-(1->4)-beta-D-Glc-(1<->1)-Cer (LacCer) (By similarity). http://togogenome.org/gene/10090:Nxph2 ^@ http://purl.uniprot.org/uniprot/Q3KP70|||http://purl.uniprot.org/uniprot/Q61199 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the neurexophilin family.|||May be proteolytically processed at the boundary between the N-terminal non-conserved and the central conserved domain in neuron-like cells.|||May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors.|||May be signaling molecules that resemble neuropeptides.|||Rodents express at detectable levels only neurexophilins-1, -3, and -4.|||Secreted http://togogenome.org/gene/10090:Pramel27 ^@ http://purl.uniprot.org/uniprot/Q4VAD2 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Tgif2lx1 ^@ http://purl.uniprot.org/uniprot/Q8K5B9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Lfng ^@ http://purl.uniprot.org/uniprot/B2RRW2|||http://purl.uniprot.org/uniprot/O09010 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A soluble form may be derived from the membrane form by proteolytic processing.|||Belongs to the glycosyltransferase 31 family.|||Detected at 12.5 dpc in all tissues examined with the highest level observed in adult brain and spleen. Detected in the dental epithelium.|||Developmental protein. During segmentation it shows a cyclic transcription pattern which is under the control of Notch. Expressed in the caudal region of the presomitic mesoderm with each cycle corresponding to the formation time of one somite. In the dental epithelium it is detected at stage 13.5 dpc. The pattern of expression corresponds exactly to the formation of the enamel knot between late bud and early cap stages.|||Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in inhibition of NOTCH1 activation by JAG1 and enhancement of NOTCH1 activation by DLL1 via an increase in its binding to DLL1 (PubMed:28089369). Decreases the binding of JAG1 to NOTCH2 but not that of DLL1 (By similarity). Essential mediator of somite segmentation and patterning. During somite boundary formation, it restricts Notch activity in the presomitic mesoderm to a boundary-forming territory in the posterior half of the prospective somite. In this region, Notch function activates a set of genes that are involved in boundary formation and in anterior-posterior somite identity (PubMed:10330372). Ectopically expressed in the thymus, Lfgn inhibits Notch signaling which results in inhibition of T-cell commitment and promotes B-cell development in lymphoid progenitors (PubMed:11520458). May play a role in boundary formation of the enamel knot (PubMed:12167404).|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Dennd6a ^@ http://purl.uniprot.org/uniprot/Q8BH65 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DENND6 family.|||Cytoplasm|||Guanine nucleotide exchange factor (GEF) for RAB14. Component of an endocytic recycling pathway that is required for the control of ADAM10 transport, shedding of N-cadherin/CDH2 by ADAM9 or ADAM10 and regulation of cell-cell junctions. Required for RAB14 recruitment to recycling endosomes (By similarity).|||Identified as having similarity to the core DENN family and referred to as DENN6A. Prediction methods do not indicate a DENN domain for this sequence and, the exact role of the DENN or the DENN-like domain in GEF activity needs to be clarified.|||Recycling endosome http://togogenome.org/gene/10090:Dytn ^@ http://purl.uniprot.org/uniprot/A2CI98 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ At 10.5 dpc, expressed largely in the brain and neural tube.|||Cell membrane|||Strongly expressed in the nervous and muscular tissues. http://togogenome.org/gene/10090:Fam24b ^@ http://purl.uniprot.org/uniprot/Q9DAL9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM24 family.|||Secreted http://togogenome.org/gene/10090:Tmem129 ^@ http://purl.uniprot.org/uniprot/Q8K304 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM129 family.|||E3 ubiquitin-protein ligase involved in ER-associated protein degradation, preferentially associates with the E2 enzyme UBE2J2. Exploited by viral US11 proteins to mediate HLA class I proteins degradation.|||Endoplasmic reticulum membrane|||Integral component of ER-resident dislocation complexes.|||The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity. http://togogenome.org/gene/10090:Barx2 ^@ http://purl.uniprot.org/uniprot/O08686 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BAR homeobox family.|||Highly expressed in small groups of cells undergoing tissue remodeling, such as ectodermal cells within indentations surrounding the eye and maxillo-nasal groove and in the first branchial pouch, lung buds, precartilagenous condensations, and mesenchyme of the limb. At 9.5 dpc, expressed only to head, prominent in the region of telencephalon and mesencephalon, and concentrated in cells along the dorsal midline. At 10.5 dpc, expression is moderated in the most rostral regions of the head, but particularly prominent in a lateral band of cells in the periocular region. At 11.5 dpc, detected in the telencephalon, frontonasal region and limbs. At 12.5 dpc, expressed in the telencephalon and hindbrain.|||Nervous system, particularly in the telencephalon, spinal cord, and dorsal root ganglia.|||Nucleus|||Transcription factor. Binds optimally to the DNA consensus sequence 5'-YYTAATGRTTTTY-3'. May control the expression of neural adhesion molecules such as L1 or Ng-CAM during embryonic development of both the central and peripherical nervous system. May be involved in controlling adhesive processes in keratinizing epithelia. http://togogenome.org/gene/10090:Slc25a22 ^@ http://purl.uniprot.org/uniprot/Q80X52|||http://purl.uniprot.org/uniprot/Q9D6M3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Membrane|||Mitochondrial glutamate/H(+) symporter. Responsible for the transport of glutamate from the cytosol into the mitochondrial matrix with the concomitant import of a proton (By similarity). Plays a role in the control of glucose-stimulated insulin secretion (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pkd1l3 ^@ http://purl.uniprot.org/uniprot/A2A258|||http://purl.uniprot.org/uniprot/Q2EG98 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the polycystin family.|||Calcium channels are probably composed of 3 subunit of PKD2L1 and 1 subunit of PKD1L3.|||Cell membrane|||Component of a calcium channel. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect.|||Expressed in a subset of taste receptor cells distinct from those involved in bitter, sweet and umami taste. Expressed in circumvallate and foliate taste buds, but not in surrounding non-gustatory lingual epithelium cells. Expressed in testis.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||No significant reduction in taste responsiveness: mice have normal nerve and behavioral responses to sour stimuli.|||Pkd1l3 and Pkd2l1 have been identified as sour taste receptor in gustatory cells based on a number of indirect evidences: Pkd2l1 is expressed in circumvallate papillae cells on the posterior part of the tongue distinct from those responsible for sweet, bitter and unami taste and genetic elimination of cells expressing Pkd2l1 reduces gustatory nerve responses to sour taste stimuli (PubMed:16891422, PubMed:16929298). However, a number of experiments have recently shown that the sour taste receptor activity is probably indirect: mice lacking Pkd1l3 do not show defects in sour taste perception (PubMed:20605874, PubMed:21625513). Moreover, the Pkd1l3-Pkd2l1 heteromer, when expressed in cells does not respond to acid stimuli used to evoke proton currents in taste cells (PubMed:21098668).|||The calcium channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application. http://togogenome.org/gene/10090:Fpr1 ^@ http://purl.uniprot.org/uniprot/P33766 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in neutrophils, dendritic cells, microglia, spleen, lung and liver. Low level of expression in the vomeronasal organ.|||High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors. Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Receptor for TAFA4, mediates its effects on chemoattracting macrophages, promoting phagocytosis and increasing ROS release (By similarity). Receptor for cathepsin CTSG, leading to increased phagocyte chemotaxis (By similarity).|||Phosphorylated; which is necessary for desensitization. http://togogenome.org/gene/10090:Kbtbd2 ^@ http://purl.uniprot.org/uniprot/G3X9X1 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subunit|||Tissue Specificity ^@ Component of the BCR(KBTBD2) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD2 and RBX1 (PubMed:27708159). Interacts (via the BTB domain) with CUL3 (PubMed:27708159).|||Expressed at high levels in muscle, liver, brain, heart as well as white and brown adipose tissues.|||In adipose tissue, expression is inhibited by diet-induced obesity, the inhibition is mediated by leptin.|||Mutants exhibit growth retardation, hyperglycemia, insulin resistance, lipodystrophy and hepatosteatosis (PubMed:27708159). Double knockouts for KBTBD2 and PIK3R1 have increased body weight, restored fat storage and decreased blood glucose and insulin (PubMed:27708159). Adipocyte-specific knockouts accumulate PIK3R1 in white and brown adipose tissues, causing insulin resistance, moderate rather than severe hyperglycemia, sustained hyperinsulinemia without late failure of insulin production and lipodystrophy leading to ectopic lipid accumulation in the liver. Adipocyte-extrinsic insulin resistance is observed in liver and muscle. None of these abnormalities are observed in liver- or muscle-specific knockout mice. Mice with knockout in adipocytes, liver and muscle show normal growth (PubMed:32381739).|||Recognizes the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex substrate, PIK3R1, through the 4 tandem C-terminal Kelch domains.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of the insulin signaling pathway, modulating insulin sensitivity by limiting PIK3R1/p85alpha abundance in adipocytes. Targets PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase (PI3K), for 'Lys-48'-linked polyubiquitination and proteasome-mediated degradation. http://togogenome.org/gene/10090:Phc3 ^@ http://purl.uniprot.org/uniprot/B7ZNA5|||http://purl.uniprot.org/uniprot/D3YY34|||http://purl.uniprot.org/uniprot/Q8CHP6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a PRC1-like complex.|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (By similarity).|||Nucleus|||Ubiquitous expression. http://togogenome.org/gene/10090:Casp4 ^@ http://purl.uniprot.org/uniprot/P70343 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) ADP-riboxanation by S.flexneri OspC3 blocks CASP4 autoprocessing, preventing CASP4 activation and ability to recognize and cleave GSDMD, thereby thwarting the inflammasome/pyroptosis-mediated defense.|||A variant of this gene has been observed in several 129 substrains, including 129/SvJ, 129S1/Sv, 129P3/J and 129S6/SvEvTac. This variant displays a 5-bp deletion encompassing the exon 7 splice acceptor junction. As a result, exon 7 is spliced out. Joining of exon 6 to exon 8 creates a frameshift after Pro-304 and a stop codon occurs after 5 aberrant amino acids. The mRNA may be the target of nonsense-mediated mRNA decay. It is detected only at low levels, while the corresponding protein is not detected at all in any of the 129 substrains tested.|||Activated by homooligomerization induced by direct binding to cytosolic LPS, in a TLR4-independent manner (PubMed:22002608, PubMed:23348507, PubMed:23887873, PubMed:24031018, PubMed:25119034). In addition to LPS, CASP4/CASP11 may also be activated by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC), in dendritic cells, promoting adaptive immunity (PubMed:27103670). The role of oxPAPC is however unclear and another report suggests that oxPAPC competes with LPS-binding and inhibits the non-canonical inflammasome in macrophages (PubMed:29520027).|||Belongs to the peptidase C14A family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit (PubMed:32109412). Upon direct LPS-binding, forms large homooligomers, resulting in its activation (PubMed:25119034). These oligomers are often referred to as 'non-canonical inflammasomes' (PubMed:25119034). In its precursor form, interacts with TMEM214; this interaction is required for association with the endoplasmic reticulum membrane (By similarity). Interacts with CASP1 (By similarity). Interacts with NOD2 (By similarity). Interacts with Serpinb1a, Serpinb1b and Serpinb1c; these interactions regulate CASP4 activity (By similarity).|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (Caspase-4 subunit p20) and a 10 kDa (Caspase-4 subunit p10) subunit.|||In response to activation signals, including cholera enterotoxin subunit B, infection by E.coli or S.typhimurium or endoplasmic reticulum stress, undergoes autoproteolytic cleavage.|||Inflammasome|||Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:22002608, PubMed:23348507, PubMed:23887873, PubMed:24031018, PubMed:25119034, PubMed:30135078, PubMed:37001519). Also indirectly activates the NLRP3 and NLRP6 inflammasomes (PubMed:26320999, PubMed:30392956, PubMed:37001519). Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 (PubMed:26375003, PubMed:28314590, PubMed:30392956). Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B and IL18 (PubMed:22002608, PubMed:22895188, PubMed:23348507, PubMed:23887873, PubMed:24031018, PubMed:26320999, PubMed:26375003, PubMed:30135078, PubMed:30589883). In the non-canonical inflammasome, CASP4/CASP11 is activated by direct binding to LPS without the need of an upstream sensor (PubMed:22002608, PubMed:23348507, PubMed:25119034, PubMed:37001519). LPS-binding promotes CASP4/CASP11 activation and CASP4/CASP11-mediated cleavage of GSDMD, followed by pyroptosis of infected cells and their extrusion into the gut lumen (PubMed:22002608, PubMed:23348507, PubMed:25119034). Also indirectly promotes secretion of mature cytokines (IL1A, IL18 and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes (By similarity). Involved in NLRP3-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin (PubMed:26320999). Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B and IL18 secretion (PubMed:30392956). Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (By similarity). The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (PubMed:23348507). Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection (PubMed:25121752, PubMed:26375003, PubMed:34671164). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752). May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC) (PubMed:27103670). Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4/CASP11 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412, PubMed:32554464). Catalyzes cleavage and maturation of IL18 (By similarity). In contrast, it does not directly process IL1B (PubMed:8702803, PubMed:9038361). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Mitochondrion|||Mutant animals are largely resistant to lipopolysaccharide (LPS)-induced lethal septic shock (PubMed:22002608, PubMed:26375259, PubMed:37001519). However, they are susceptible to Burkholderia thailandensis infection, even at low bacterial doses (PubMed:26320999). During intestinal Salmonella Typhimurium infection, mutant animals display higher pathogen loads in their cecal tissues and lumen and lower levels of IL18 in cecal explants, associated with a significant reduction in cecal inflammation (PubMed:25121752). Bone-marrow-derived macrophages from knockout mice respond normally, in terms of IL1B secretion, to canonical inflammasome activators, such as ATP, monosodium urate, poly(dA:dT) double-stranded DNA, Francisella tularensis, flagellin or Pseudomonas aeruginosa, but fail to secrete IL1B in response to cholera enterotoxin subunit B or LPS (PubMed:22002608, PubMed:37001519). They also do not respond to live E.coli, C.rodentium and V.cholerae, with or without LPS priming (PubMed:22002608).|||Secreted|||The CARD domain mediates LPS recognition and homooligomerization.|||Up-regulated by LPS and E.coli (PubMed:8702803, PubMed:10986288, PubMed:22002608, PubMed:26375259). In LPS-induced lung inflammation, markedly up-regulated after 6 hours of treatment and decreases at 24 hours. The induction is dependent upon DDIT3/CHOP-mediated ER stress (at protein level) (PubMed:16670335). In the spleen and in bone marrow-derived macrophages, up-regulated by poly(I:C), a synthetic analog of double-stranded RNA (at protein level) (PubMed:26320999, PubMed:26375259). Also induced by IFNG and interferon-alpha. Up-regulated by R848, a TLR7 synthetic activator, and Pam3CysK4, a synthetic activator of TLR1/TLR2 (PubMed:26375259).|||Widely expressed, including in thymus, lung and spleen (at protein level). Very low levels, if any, in the brain.|||cytosol http://togogenome.org/gene/10090:B4galnt4 ^@ http://purl.uniprot.org/uniprot/Q766D5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the chondroitin N-acetylgalactosaminyltransferase family.|||Golgi stack membrane|||Transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine-beta-benzyl with a beta-1,4-linkage to form N,N'-diacetyllactosediamine, GalNAc-beta-1,4-GlcNAc structures in N-linked glycans and probably O-linked glycans. http://togogenome.org/gene/10090:Taldo1 ^@ http://purl.uniprot.org/uniprot/Q93092 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transaldolase family. Type 1 subfamily.|||Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway. Catalyzes the reversible conversion of sedheptulose-7-phosphate and D-glyceraldehyde 3-phosphate into erythrose-4-phosphate and beta-D-fructose 6-phosphate (PubMed:17003133, PubMed:27703206). Not only acts as a pentose phosphate pathway enzyme, but also affects other metabolite pathways by altering its subcellular localization between the nucleus and the cytoplasm (PubMed:27703206).|||Cytoplasm|||Deficient mice develop normally; however, males are sterile because of functional and structural defects of mitochondria (PubMed:17003133). Mice spontaneously develop hepatocellular carcinoma. The liver of these mice present an accumulation of five-carbon sugarphosphates and a depletion of NADPH and GSH (PubMed:19436114).|||Homodimer (PubMed:27703206). Heterodimer with isoform 2 (PubMed:27703206). Interacts with KPNA1 and KPNA4 (PubMed:27703206).|||Nucleus|||The first 10 amino acids are essential for nuclear localization. http://togogenome.org/gene/10090:Prrg4 ^@ http://purl.uniprot.org/uniprot/Q8BGN6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the commissureless family.|||Cell membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.|||Interacts (via cytoplasmic domain) with WW domain-containing proteins MAGI1, MAGI3, NEDD4, NEDD4L, WWTR1/TAZ and YAP1.|||May control axon guidance across the CNS (By similarity). Prevents the delivery of ROBO1 at the cell surface and down-regulates its expression (By similarity). http://togogenome.org/gene/10090:Gnpda2 ^@ http://purl.uniprot.org/uniprot/Q9CRC9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by N-acetylglucosamine-6-phosphate (GlcNAc6P).|||Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.|||Catalyzes the reversible conversion of alpha-D-glucosamine 6-phosphate (GlcN-6P) into beta-D-fructose 6-phosphate (Fru-6P) and ammonium ion, a regulatory reaction step in de novo uridine diphosphate-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) biosynthesis via hexosamine pathway. Deamination is coupled to aldo-keto isomerization mediating the metabolic flux from UDP-GlcNAc toward Fru-6P. At high ammonium level can drive amination and isomerization of Fru-6P toward hexosamines and UDP-GlcNAc synthesis. Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and their effects on hyaluronan synthesis that occur during tissue remodeling.|||Cytoplasm|||Homohexamer. http://togogenome.org/gene/10090:Ly6g5c ^@ http://purl.uniprot.org/uniprot/Q8K1T5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in adult brain.|||Forms oligomers.|||May have a role in hematopoietic cell differentiation.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:L3mbtl2 ^@ http://purl.uniprot.org/uniprot/G3UY70|||http://purl.uniprot.org/uniprot/P59178|||http://purl.uniprot.org/uniprot/Q80XB1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Nucleus|||Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, BAT8 and YAF2.|||Phosphorylated.|||Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Its association with a chromatin-remodeling complex suggests that it may contribute to prevent expression of genes that trigger the cell into mitosis. Binds to monomethylated and dimethylated 'Lys-20' on histone H4. Binds histone H3 peptides that are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27' (By similarity).|||Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Its association with a chromatin-remodeling complex suggests that it may contribute to prevent expression of genes that trigger the cell into mitosis. Binds to monomethylated and dimethylated 'Lys-20' on histone H4. Binds histone H3 peptides that are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27'.|||Ubiquitous. http://togogenome.org/gene/10090:Vmn1r181 ^@ http://purl.uniprot.org/uniprot/Q0P547 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il6ra ^@ http://purl.uniprot.org/uniprot/A0A0G2JGF1|||http://purl.uniprot.org/uniprot/P22272|||http://purl.uniprot.org/uniprot/Q3URV7 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A short soluble form is also released from the membrane by proteolysis (PubMed:26876177). The sIL6R is formed by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding (PubMed:26876177). mIL6R is cleaved by the proteases ADAM10 and ADAM17 (PubMed:26876177).|||Also interacts with SORL1; this interaction leads to soluble IL6R internalization. May form a trimeric complex with the soluble SORL1 ectodomain and circulating IL6 receptor; this interaction might stabilize circulating IL6, hence promote IL6 'trans-signaling'.|||Belongs to the type I cytokine receptor family. Type 3 subfamily.|||Cell membrane|||Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling.|||Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6 to associate with the signaling subunit IL6ST (PubMed:28265003). Interacts (via N-terminal ectodomain) with SORL1; this interaction may affect IL6-binding to IL6R, hence decrease IL6 'classic-signaling' (PubMed:28265003).|||Detected in the cerebrospinal fluid.|||Expressed by dendritic cells.|||Glycosylated. Glycosylation is dispensable for transport, signaling, and cell-surface turnover. Glycosylation at Asn-55 is a protease-regulatory exosite. Glycosylation is required for ADAM17-mediated proteolysis.|||Levels in the cerebrospinal fluid are increased in obese mice.|||Membrane|||Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis. The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells.|||Secreted|||Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (PubMed:27893700).|||Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:11113088). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (By similarity). In complex with IL6, is required for induction of VEGF production (By similarity). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (PubMed:11113088). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (PubMed:28402851).|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The two fibronectin type-III-like domains contained in the C-terminal part form together a cytokine-binding domain. http://togogenome.org/gene/10090:Rims3 ^@ http://purl.uniprot.org/uniprot/Q80U57 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds PPFIA3 (By similarity). Does not bind RAB3.|||Regulates synaptic membrane exocytosis.|||Synapse http://togogenome.org/gene/10090:Polr2j ^@ http://purl.uniprot.org/uniprot/Q3TYI2|||http://purl.uniprot.org/uniprot/Q6PI63 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft.|||Nucleus http://togogenome.org/gene/10090:Calb2 ^@ http://purl.uniprot.org/uniprot/Q08331 ^@ Function|||Similarity ^@ Belongs to the calbindin family.|||Calretinin is a calcium-binding protein which is abundant in auditory neurons. http://togogenome.org/gene/10090:Golga1 ^@ http://purl.uniprot.org/uniprot/Q9CW79 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Extended rod-like protein with coiled-coil domains.|||Interacts with RAB6A (By similarity). Directly interacts with TBC1D23 (PubMed:29084197). Interacts with FAM91A1; this interaction may be mediated by TBC1D23 (Probable).|||Involved in vesicular trafficking at the Golgi apparatus level. Involved in endosome-to-Golgi trafficking.|||Present in the acrosome of spermatids up to the late cap-stage, but not in mature spermatozoa.|||acrosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Otc ^@ http://purl.uniprot.org/uniprot/P11725|||http://purl.uniprot.org/uniprot/Q543H3 ^@ Activity Regulation|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-88 negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals.|||Belongs to the aspartate/ornithine carbamoyltransferase superfamily.|||Belongs to the aspartate/ornithine carbamoyltransferase superfamily. OTCase family.|||Catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline. The urea cycle ensures the detoxification of ammonia by converting it to urea for excretion.|||Defects in Otc are the cause of the Sparse fur (spf) phenotype. Spf mouse have an OTCase with an overall decrease in activity, and altered substrate affinity.|||Homotrimer.|||Mitochondrion matrix|||Negatively regulated by lysine acetylation. http://togogenome.org/gene/10090:Rps2 ^@ http://purl.uniprot.org/uniprot/P25444|||http://purl.uniprot.org/uniprot/Q58EU3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Asymmetric arginine dimethylation by PRMT3 occurs at multiple sites in the Arg/Gly-rich region.|||Belongs to the universal ribosomal protein uS5 family.|||Citrullinated by PADI4 in the Arg/Gly-rich region.|||Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:36517592). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:36517592). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:36517592). Plays a role in the assembly and function of the 40S ribosomal subunit (By similarity). Mutations in this protein affects the control of translational fidelity (By similarity). Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). Interacts with zinc finger protein ZNF277 (via zinc-finger domains); the interaction is direct; the interaction is extra-ribosomal (By similarity). Interaction with ZNF277 competes with the binding of RPS2 to protein arginine methyltransferase PRMT3 (By similarity).|||Cytoplasm|||Monoubiquitinated at Lys-54 and Lys-58 by RNF10 when a ribosome has stalled during translation, leading to its degradation by the proteasome. Deubiquitinated at Lys-54 and Lys-58 by USP10, preventing degradation by the proteasome and promoting 40S ribosome subunit recycling following ribosome dissociation.|||nucleolus http://togogenome.org/gene/10090:Psmb11 ^@ http://purl.uniprot.org/uniprot/Q8BG41 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase T1B family.|||Cytoplasm|||Displays defective development of CD8-positive T-cells in the thymus.|||Expressed exclusively in cortical thymic epithelial cells.|||Nucleus|||The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Incorporated instead of PSMB5 and PSMB8.|||The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome. Plays a pivotal role in development of CD8-positive T-cells. http://togogenome.org/gene/10090:Slc25a38 ^@ http://purl.uniprot.org/uniprot/Q91XD8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family. SLC25A38 subfamily.|||Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix. Plays an important role in providing glycine for the first enzymatic step in heme biosynthesis, the condensation of glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the mitochondrial matrix. Required during erythropoiesis.|||Mitochondrion inner membrane|||Plays a role as pro-apoptotic protein that induces caspase-dependent apoptosis. http://togogenome.org/gene/10090:Ppib ^@ http://purl.uniprot.org/uniprot/P24369|||http://purl.uniprot.org/uniprot/Q9DCY1 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclophilin-type PPIase family.|||Belongs to the cyclophilin-type PPIase family. PPIase B subfamily.|||Endoplasmic reticulum lumen|||Expressed in the kidney thick ascending limb (at protein level).|||Inhibited by cyclosporin A (CsA).|||Interacts with DYM. Interacts with CALR, CLGN and CANX. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.|||It is uncertain whether Met-1 or Met-9 is the initiator.|||Melanosome|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. http://togogenome.org/gene/10090:Slc2a9 ^@ http://purl.uniprot.org/uniprot/Q3T9X0 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.|||Conditional knockout mice lacking Slc2a9 in enterocytes are born at the expected Mendelian rate; they show no obvious phenotype and are fertile (PubMed:25100214). Mice however develop impaired enterocyte uric acid transport kinetics, hyperuricaemia, hyperuricosuria, spontaneous hypertension, dyslipidaemia and elevated body fat (PubMed:25100214).|||High-capacity urate transporter that was first described as a fructose and glucose transporter. Also described in the literature as high-affinity and low-capacity glucose and fructose transporter (By similarity). However, another group could not confirm transporter activity for glucose or fructose (By similarity).|||High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules. May have a residual high-affinity, low-capacity glucose and fructose transporter activity. Transports urate at rates 45- to 60-fold faster than glucose. Does not transport galactose. May mediate small uptake of adenine but not of other nucleobases.|||Highly expressed in the intestine, with high expression in the jejunum and ileum, the segments of the intestine that perform the majority of urate excretion (PubMed:25100214). Isoform 1: Widely expressed (PubMed:16293642). Isoform 1: In kidney, expressed at low levels in proximal tubules (PubMed:19587147). Isoform 2: Primarily expressed in liver and kidney; with specific expression in distal convoluted and connecting tubules of kidney (PubMed:16293642, PubMed:19587147).|||N-glycosylated. http://togogenome.org/gene/10090:Actg1 ^@ http://purl.uniprot.org/uniprot/P63260|||http://purl.uniprot.org/uniprot/Q4KL81 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.|||Belongs to the actin family.|||In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.|||Methylated at His-73 by SETD3.|||Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.|||N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins. In contrast, filament nucleation by the Arp2/3 complex is not affected.|||N-terminal cleavage of acetylated methionine of immature cytoplasmic actin by ACTMAP.|||Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form (PubMed:23911929). The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization (PubMed:23911929).|||Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with TWF1, CAPZB, cofilin and profilin.|||cytoskeleton http://togogenome.org/gene/10090:Or8g32 ^@ http://purl.uniprot.org/uniprot/Q9EQ94 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Bok ^@ http://purl.uniprot.org/uniprot/O35425|||http://purl.uniprot.org/uniprot/Q3TH93 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Matador' means killer in Spanish.|||Apoptosis regulator that functions through different apoptotic signaling pathways (PubMed:23429263, PubMed:26015568, PubMed:26949185, PubMed:27098698, PubMed:9535847). Plays a roles as pro-apoptotic protein that positively regulates intrinsic apoptotic process in a BAX- and BAK1-dependent manner or in a BAX- and BAK1-independent manner (PubMed:23429263, PubMed:26015568, PubMed:26949185). In response to endoplasmic reticulum stress promotes mitochondrial apoptosis through downstream BAX/BAK1 activation and positive regulation of PERK-mediated unfolded protein response (PubMed:26015568). Activates apoptosis independently of heterodimerization with survival-promoting BCL2 and BCL2L1 through induction of mitochondrial outer membrane permeabilization, in a BAX- and BAK1-independent manner, in response to inhibition of ERAD-proteasome degradation system, resulting in cytochrome c release (PubMed:9535847, PubMed:26949185). In response to DNA damage, mediates intrinsic apoptotic process in a TP53-dependent manner. Plays a role in granulosa cell apoptosis by CASP3 activation (By similarity). Plays a roles as anti-apoptotic protein during neuronal apoptotic process, by negatively regulating poly ADP-ribose polymerase-dependent cell death through regulation of neuronal calcium homeostasis and mitochondrial bioenergetics in response to NMDA excitation (PubMed:27098698). In addition to its role in apoptosis, may regulate trophoblast cell proliferation during the early stages of placental development, by acting on G1/S transition through regulation of CCNE1 expression.May also play a role as an inducer of autophagy by disrupting interaction between MCL1 and BECN1 (By similarity).|||At 15.0 dpc, expressed in brain, liver, thymus, lung, intestinal epithelium and follicles of the whiskers.|||BH4 domain mediates interaction with ITPR1.|||Belongs to the Bcl-2 family.|||Cytoplasm|||Early endosome membrane|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Induced upon proteasome inhibition.|||Knockout Bok mice have a normal development.|||Membrane|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion membrane|||Mitochondrion outer membrane|||Monomer; positively regulates apoptotic process. Homodimer (PubMed:23429263). Heterodimer (By similarity). Oligomer; promoted by apoptotic stimuli and BH3-only proteins; mediates constitutive activation (PubMed:26949185). Interacts (via BH4 domain) with ITPR1; enhances BOK expression and stabilization; limits apoptosis and prevents ubiquitination and then degradation; protects ITPR1 from proteolysis by CASP3 during apoptosis (PubMed:27053113, PubMed:23884412). Interacts with ITPR2 and ITPR3; binds most strongly to ITPR2, and barely to ITPR3; regulates their expression (PubMed:23884412). Interacts with XPO1; translocates to the cytoplasm (By similarity). Interacts with BNIP3; promotes oligomerization (By similarity).|||Nucleus|||Nucleus outer membrane|||Recycling endosome membrane|||Ubiquitinated by AMFR/gp78 E3 ubiquitin ligase complex; mediates degradation by ubiquitin-proteasome pathway in a VCP/p97-dependent manner; prevents from proapoptotic activity; promotes degradation of newly synthesized proteins that are not ITPR1 associated.|||Widely expressed (PubMed:9535847, PubMed:23429263). Highly expressed in brain, kidney, and spleen (PubMed:27098698).|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ywhag ^@ http://purl.uniprot.org/uniprot/A8IP69|||http://purl.uniprot.org/uniprot/P61982 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24.|||Belongs to the 14-3-3 family.|||Cytoplasm|||Homodimer (By similarity). Interacts with SAMSN1 (PubMed:20478393). Interacts with RAF1, SSH1 and CRTC2/TORC2 (By similarity). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (By similarity). Interacts with GAB2 (By similarity). Interacts with MDM4 (phosphorylated); negatively regulates MDM4 activity toward TP53 (By similarity). Interacts with PKA-phosphorylated AANAT and SIRT2 (By similarity). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (By similarity). Interacts with SLITRK1 (By similarity). Interacts with LRRK2; this interaction is dependent on LRRK2 phosphorylation (By similarity). Interacts with MARK2 and MARK3 (By similarity). Interacts with MEFV (By similarity). Interacts with ENDOG, TSC2 and PIK3C3; interaction with ENDOG weakens its interaction with TSC2 and PIK3C3 (By similarity). Interacts with (phosphorylated) WDR24 (By similarity).|||Phosphorylated by various PKC isozymes. http://togogenome.org/gene/10090:Defb22 ^@ http://purl.uniprot.org/uniprot/Q8BVC1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||O-glycosylated; glycans contain alpha(2,3)-linked sialic acids.|||Probable component of sperm glycocalyx. Likely protects and facilitates transport of sperm in the female reproductive tract. Probably released from the sperm surface during capacitation.|||Specifically expressed in corpus epididymis and cauda epididymis with expression in corpus being highest (at protein level). Not detected in other tissues tested, including testis, prostate, seminal vesicle and vas deferens (at protein level).|||acrosome|||extracellular space http://togogenome.org/gene/10090:Bmpr2 ^@ http://purl.uniprot.org/uniprot/O35607|||http://purl.uniprot.org/uniprot/Q3UER5|||http://purl.uniprot.org/uniprot/Q3UG09 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Interacts with GDF5 (By similarity). Interacts with BMP4 (By similarity). Interacts with SCUBE3 (By similarity). Interacts with TSC22D1/TSC-22 (By similarity).|||On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6 (PubMed:23527555). http://togogenome.org/gene/10090:Mxi1 ^@ http://purl.uniprot.org/uniprot/P50540 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with SMC3. Interacts with RNF17.|||Nucleus|||Primarily expressed in differentiating cells. Also expressed in the proliferating cells of the developing CNS and the epidermis. In the spinal cord at embryonic day 10.5, expressed in the ventricular zone of the neural tube. Expressed at highest levels in cells accumulating in the intermediate zone. At 11.5 and 12.5 dpc, highly expressed in the intermediate zone and at reduced levels in the ventricular zone that mostly persists in the dorsal part of the neural tube. At 14.5 dpc, expressed throughout the spinal cord. In the developing epidermis at 14.5 dpc, found in the dorsal lateral epidermis. At 17 dpc, expression is restricted not only to the differentiating cells of the epidermis but also to the proliferating cell compartment and expression extends into the first differentiating cell layers, but decreases in the uppermost layers of the epidermis.|||Transcriptional repressor. MXI1 binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. MXI1 thus antagonizes MYC transcriptional activity by competing for MAX. Isoform Short, which lacks a segment, has a much stronger suppressive potential and associates with a SIN3 homologous protein. http://togogenome.org/gene/10090:Or2j6 ^@ http://purl.uniprot.org/uniprot/Q8VGL2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Itsn1 ^@ http://purl.uniprot.org/uniprot/Q9Z0R4 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery (PubMed:10064583). Acts as guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex (By similarity). Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits (By similarity). Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (PubMed:16914641). Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2 (By similarity). Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways (PubMed:16914641). In chromaffin cells, required for normal exocytosis of catecholamines (PubMed:18676989). Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones (PubMed:23633571). Inhibits ARHGAP31 activity toward RAC1 (By similarity).|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Detected in brain, adrenal gland and heart (PubMed:16914641, PubMed:18676989). Detected in neurons at the calyx of Held (at protein level) (PubMed:23633571). Isoform 1: Primarily detected in brain neurons. Isoform 2: Primarily detected in glia (at protein level) (PubMed:18676989). Widely expressed. Expressed at high levels in brain, heart and skeletal muscle (PubMed:10064583).|||Endomembrane system|||Endosome|||In an autoinhibited form the SH3 domain 5 may bind intramolecularly to the DH domain, thus blocking the CDC42-binding site.|||Interacts (via DH domain) with CDC42. Interacts (via SH3 domain 1) with WASL (By similarity). Interacts with dynamin, SNAP25 and SNAP23 (By similarity). Interacts with clathrin-associated proteins and other components of the endocytic machinery, such as SPIN90, EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2 (PubMed:10064583, PubMed:20448150). Interacts (via SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31 (PubMed:11744688). Interacts with ADAM15 (By similarity). Interacts with PRRT2 (PubMed:26797119). Interacts (via SH3 domain 4) with FCHSD2 (via SH3 domain 2). Interacts (via SH3 domain 1) with DENND2B (By similarity). Interacts (via SH3 domains) with CBL (PubMed:16914641). Isoform 2: Interacts with CBL and DNM1. Isoform 2: Interacts with LMNA (By similarity). Isoform 2: Interacts with importin subunit KPNA1; this is likely to mediate its import into the nucleus (PubMed:29599122).|||No visible phenotype, except that about 13% of the pups do not thrive. Mice are born at the expected Mendelian rate (PubMed:18676989). Mutant mice display no obvious defects in synaptic responses to single stimuli at the calyx of Held. Repetitive stimulation gives rise to decreased synaptic responses, due to perturbation of the replenishment of release-ready synaptic vesicles (PubMed:23633571).|||Nucleus envelope|||Overexpression results in the inhibition of the transferrin uptake and the blockage of the clathrin-mediated endocytosis.|||Plays a role in synaptic vesicle endocytosis in brain neurons.|||Recycling endosome|||SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin (By similarity). SH3-1 and SH3-4 bind to ARHGAP31.|||The KLERQ domain binds to SNAP-25 and SNAP-23.|||clathrin-coated pit|||lamellipodium|||synaptosome http://togogenome.org/gene/10090:Fam76b ^@ http://purl.uniprot.org/uniprot/Q80XP8 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM76 family.|||Nucleus speckle|||The polyhistidine repeat acts as a targeting signal to nuclear speckles. http://togogenome.org/gene/10090:Slc22a22 ^@ http://purl.uniprot.org/uniprot/Q8R0S9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Sodium-independent organic anion transporter which exhibits high specificity for a subset of prostaglandins including prostaglandin E2 (PGE2), prostaglandin E1 (PGE1), prostaglandin F2-alpha (PGF2-alpha) and prostaglandin D2 (PGD2).|||Specifically expressed in kidney where it is found in proximal convoluted tubules (at protein level). Colocalizes with the prostaglandin-inactivating enzyme HPGD in kidney (at protein level). Not detected in other tissues tested. http://togogenome.org/gene/10090:Pex13 ^@ http://purl.uniprot.org/uniprot/Q9D0K1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxin-13 family.|||Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (By similarity). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix. Involved in the import of PTS1- and PTS2-type containing proteins (By similarity).|||Interacts (via SH3 domain) with PEX14 (via SH3-binding motif); forming the PEX13-PEX14 docking complex. Interacts with PEX19.|||Peroxisome membrane http://togogenome.org/gene/10090:Ido1 ^@ http://purl.uniprot.org/uniprot/D3YXV1|||http://purl.uniprot.org/uniprot/P28776 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activity is inhibited by and MTH-trp (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan).|||Belongs to the indoleamine 2,3-dioxygenase family.|||Binds 1 heme group per subunit.|||By IFNG/IFN-gamma in most cells.|||Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway. Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells. Acts as a suppressor of anti-tumor immunity (PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan. Protects the fetus from maternal immune rejection (PubMed:15063630).|||Highly expressed in epididymis, duodemum, jejunum, ileum, colon and spleen (PubMed:19741271). Highly expressed in epididymis, prostate, duodemum, jejunum, ileum, colon and spleen, not detected in the liver (at protein level) (PubMed:19741271). Expressed in tumors only upon exposure to IFN gamma (PubMed:25691885). Constitutively expressed in placenta in trophoblast cells (PubMed:15063630). Expression is restricted to perinuclear regions of primary trophoblast giant cells (TGCs) of fetal origin at mid-gestation (10.5 dpc). After placentation (14 dpc), no IDO expression was detected at the maternal-fetal interface (PubMed:15063630).|||Ido1 and Ido2 are 2 distinct enzymes which catalyze the same reaction. Ido2 affinity for tryptophan is much lower than that of Ido1. Ido2 may play a role as a negative regulator of Ido1 by competing for heme-binding with Ido1. Low efficiency Ido2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency Ido1 enzymes are dispensable in many lower vertebrate lineages. Ido1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals.|||Knockout mice display normal development and function of dendritic cells, on T- or B-cells development (PubMed:18384884). They display increased sensitivity to the induction of inflammatory and autoimmune reactions (PubMed:22157149). They produce litters of normal sizes at normal rates, implying that compensatory or redundant immunosuppressive mechanisms protected allogeneic fetuses during gestation in knockout mice. Knockout mice display cardiac and gastrointestinal liabilities (PubMed:22157149).|||Monomer.|||cytosol http://togogenome.org/gene/10090:Wdr90 ^@ http://purl.uniprot.org/uniprot/Q6ZPG2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat WDR90/POC16 family.|||Required for efficient primary cilium formation.|||centriole http://togogenome.org/gene/10090:Sval3 ^@ http://purl.uniprot.org/uniprot/Q76I99 ^@ Similarity|||Subunit ^@ Belongs to the PIP family.|||Monomer. Interacts with AZGP1. http://togogenome.org/gene/10090:Dpy19l4 ^@ http://purl.uniprot.org/uniprot/A2AJQ3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the dpy-19 family.|||Membrane|||Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins. http://togogenome.org/gene/10090:F8 ^@ http://purl.uniprot.org/uniprot/B2RRC9|||http://purl.uniprot.org/uniprot/B7ZNH8|||http://purl.uniprot.org/uniprot/Q06194|||http://purl.uniprot.org/uniprot/Q8BQ43 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the multicopper oxidase family.|||Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.|||Found in most tissues.|||Interacts with vWF. vWF binding is essential for the stabilization of F8 in circulation (By similarity).|||Proteolytically cleaved by cathepsin CTSG to produce a partially activated form.|||The binding of vWF and activation depend on the sulfation of Tyr-1669.|||extracellular space http://togogenome.org/gene/10090:Gstt4 ^@ http://purl.uniprot.org/uniprot/Q9D4P7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Theta family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Napepld ^@ http://purl.uniprot.org/uniprot/Q8BH82 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by divalent cations (PubMed:17655883). Activated by bile acids (By similarity). Activated by membrane phospholipids such as phosphatidylethanolamines (PubMed:17655883).|||Belongs to the NAPE-PLD family.|||Binds 2 zinc divalent cations per subunit.|||D-type phospholipase that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce bioactive N-acylethanolamines/fatty acid ethanolamides (NAEs/FAEs) and phosphatidic acid (PubMed:14634025, PubMed:15760304, PubMed:17655883, PubMed:21801852). Cleaves the terminal phosphodiester bond of diacyl- and alkenylacyl-NAPEs, primarily playing a role in the generation of long-chain saturated and monounsaturated NAEs in the brain (PubMed:21801852, PubMed:16605240). May control NAPE homeostasis in dopaminergic neuron membranes and regulate neuron survival, partly through RAC1 activation (PubMed:31685899). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose (PubMed:25757720). Has limited D-type phospholipase activity toward N-acyl lyso-NAPEs (PubMed:14634025).|||Down-regulated by neurotoxin 6-hydroxydopamine.|||Early endosome membrane|||Golgi apparatus membrane|||Homodimer. Bile acids promote the assembly of inactive monomers into an active dimer and enable catalysis.|||Knockout mice are born at the expected Mendelian rate (PubMed:16605240). White adipose-tissue specific knockdown (effective when differentiation of adipose tissue is complete) causes obesity, adipose tissue inflammation, insulin resistance in the liver and profound changes of gut microbiota composition.|||Nucleus envelope|||Widely expressed. Highest expression in brain, spinal cord, kidney and testis (at protein level) (PubMed:14634025, PubMed:16605240). Expressed in adipose tissue (at protein level) (PubMed:25757720).|||nucleoplasm http://togogenome.org/gene/10090:Klhl41 ^@ http://purl.uniprot.org/uniprot/A2AUC9 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in the myotome part of the mature somites in embryos from embryonic day 9.5 onwards. It is not expressed in the developing heart at these embryonic stages.|||Interacts with NRAP. Part of a complex that contains CUL3, RBX1 and KLHL41. Interacts with LASP1.|||Involved in skeletal muscle development and differentiation. Regulates proliferation and differentiation of myoblasts and plays a role in myofibril assembly by promoting lateral fusion of adjacent thin fibrils into mature, wide myofibrils. Required for pseudopod elongation in transformed cells.|||M line|||Sarcoplasmic reticulum membrane|||Skeletal muscle. Localized between laterally fusing myofibrils in skeletal muscle (at protein level). Expressed at a lower level in the heart compared to skeletal muscle.|||Ubiquitinated by E3 ubiquitin ligase complex formed by CUL3 and RBX1 and probably targeted for proteasome-independent degradation. Quinone-induced oxidative stress increases its ubiquitination.|||cytoskeleton|||pseudopodium|||ruffle http://togogenome.org/gene/10090:Slc30a2 ^@ http://purl.uniprot.org/uniprot/D3Z5N1|||http://purl.uniprot.org/uniprot/Q2HJ10 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Cell membrane|||Down-regulated upon zinc starvation (at protein level). Up-regulated upon zinc intake (PubMed:20133611). Up-regulated by dexamethasone (PubMed:20133611).|||Electroneutral proton-coupled antiporter concentrating zinc ions into a variety of intracellular organelles including endosomes, zymogen granules and mitochondria. Thereby, plays a crucial role in cellular zinc homeostasis to confer upon cells protection against its potential cytotoxicity (PubMed:21289295). Regulates the zinc concentration of milk, through the transport of zinc ions into secretory vesicles of mammary cells (Probable). By concentrating zinc ions into lysosomes participates to lysosomal-mediated cell death during early mammary gland involution (By similarity).|||Electroneutral proton-coupled antiporter mediating the efflux of zinc ions through the plasma membrane.|||Endosome membrane|||Homodimer. Interacts (via lysosomal targeting motif) with AP3D1; in AP-3-mediated transport to lysosomes. Interacts with TMEM163.|||Lysosome membrane|||Membrane|||Mitochondrion inner membrane|||Phosphorylated at Ser-295. Phosphorylation at Ser-295 prevents localization to lysosomes. Dephosphorylation of Ser-295 which triggers localization to lysosomes, accumulation of zinc into lysosomes and lysosomal-mediated cell death is induced by TNF-alpha.|||Zymogen granule membrane|||secretory vesicle membrane http://togogenome.org/gene/10090:Inip ^@ http://purl.uniprot.org/uniprot/Q3TXT3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SOSS-C family.|||Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways (By similarity).|||Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1. Interacts with INTS3; the interaction is direct (By similarity).|||Nucleus http://togogenome.org/gene/10090:Fam24a ^@ http://purl.uniprot.org/uniprot/Q8CF27 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM24 family.|||Secreted http://togogenome.org/gene/10090:Or9k7 ^@ http://purl.uniprot.org/uniprot/Q8VEV5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Wipi1 ^@ http://purl.uniprot.org/uniprot/Q8R3E3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat PROPPIN family.|||Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:22275429). Plays an important role in starvation- and calcium-mediated autophagy, as well as in mitophagy. Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and maybe other phosphoinositides including PtdIns3,5P2 and PtdIns5P, and is recruited to phagophore assembly sites at the endoplasmic reticulum membranes. There, it assists WIPI2 in the recruitment of ATG12-ATG5-ATG16L1, a complex that directly controls the elongation of the nascent autophagosomal membrane. Together with WDR45/WIPI4, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes. Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Also plays a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway (By similarity).|||Endosome|||Interacts with androgen receptor (AR) and the estrogen receptors ESR1 and ESR2. Interacts with WIPI2. Interacts with WDR45. Interacts with ATG16L1. May interact with NUDC.|||Preautophagosomal structure membrane|||The L/FRRG motif is required for recruitment to PtdIns3P.|||The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P).|||clathrin-coated vesicle|||cytoskeleton|||trans-Golgi network http://togogenome.org/gene/10090:Necab3 ^@ http://purl.uniprot.org/uniprot/Q9D6J4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Golgi apparatus|||Inhibits the interaction of APBA2 with amyloid-beta precursor protein (APP), and hence allows formation of amyloid-beta (By similarity). May enhance the activity of HIF1A and thus promote glycolysis under normoxic conditions; the function requires its ABM domain and may implicate the stabilization of the interaction between HIF1AN and APBA3 (By similarity).|||Interacts with the N-terminal domain of APBA2. Interacts with NEK2 (By similarity). Interacts with APBA3; APBA3 seems to mediate the interaction between NECAB3 and HIF1AN (By similarity).|||Phosphorylated by NEK2.|||Widely expressed, with highest levels in the brain. http://togogenome.org/gene/10090:Casp12 ^@ http://purl.uniprot.org/uniprot/E9Q575|||http://purl.uniprot.org/uniprot/O08736 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C14A family.|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by two subunits (Potential). Interacts with TRAF2 under resting conditions; this interaction is reduced in ER stress conditions.|||Involved in the activation cascade of caspases responsible for apoptosis execution.|||Mainly expressed in skeletal muscle and lung. http://togogenome.org/gene/10090:1700014D04Rik ^@ http://purl.uniprot.org/uniprot/J3QMS2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Rybp ^@ http://purl.uniprot.org/uniprot/Q8CCI5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.0 dpc, selectively expressed in cells of the developing nervous system and from day E.5 onwards, expressed ubiquitously.|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1-like complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:22325148, PubMed:28596365). Component of a PRC1-like complex that mediates monoubiquitination of histone H2A 'Lys-119' on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females (PubMed:28596365). May stimulate ubiquitination of histone H2A 'Lys-119' by recruiting the complex to target sites (PubMed:22325148, PubMed:28596365). Inhibits ubiquitination and subsequent degradation of TP53, and thereby plays a role in regulating transcription of TP53 target genes (By similarity). May also regulate the ubiquitin-mediated proteasomal degradation of other proteins like FANK1 to regulate apoptosis (PubMed:17874297). May be implicated in the regulation of the transcription as a repressor of the transcriptional activity of E4TF1 (By similarity). May bind to DNA (PubMed:19170609). May play a role in the repression of tumor growth and metastasis in breast cancer by down-regulating SRRM3 (PubMed:27748911).|||Cytoplasm|||Embryonically lethal. Embryos die at early postimplantation stage.|||Expressed in embryonic stem cells.|||Intrinsically unstructured in the absence of binding partners. Folds upon binding to DNA or RNF2.|||Monomer. Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of BCOR, PCGF1, RING1 and RNF2/RING2 (By similarity). Component of PCR1-like complexes (PubMed:22325148, PubMed:28596365). Interacts with PCGF1. Part of a PCR1-like complex that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP. Interacts with RNF2; the interaction is direct (By similarity). Interacts with CBX2, YAF2, RING1 and RNF2 (PubMed:10369680, PubMed:19170609, PubMed:22226355). Interacts with ubiquitin and ubiquitinated proteins (PubMed:17070805). Interacts with ubiquitinated histone H2A (PubMed:17070805). Interacts with apoptin, DEDD, FADD, CASP8, CASP10, YY1 and GABPB1. Together with GABPB1 and YY1, it forms a ternary complex, probably being the bridge factor between these two transcription factors. Interacts with MDM2, and thereby inhibits ubiquitination of TP53. Identified in a ternary complex containing MDM2, TP53 and RYBP. Interacts with FANK1; may prevent the ubiquitin-mediated proteasomal degradation of FANK1 (By similarity). Interacts with IFT57 (PubMed:17874297).|||Monoubiquitinated.|||Nucleus|||nucleoplasm http://togogenome.org/gene/10090:Frmd8 ^@ http://purl.uniprot.org/uniprot/Q3UFK8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with iRhom proteins, including iRhom2/RHBDF2 (via cytoplasmic N-termini); this interaction leads to mutual protein stabilization (PubMed:29897336). Interacts with LRP6; this interaction affects LRP6-binding to AXIN1 (By similarity).|||Mutant mice are viable and fertile.|||Promotes the cell surface stability of iRhom1/RHBDF1 and iRhom2/RHBDF2 and prevents their degradation via the endolysosomal pathway (PubMed:29897333). By acting on iRhoms, involved in ADAM17-mediated shedding of TNF, amphiregulin/AREG, HBEGF and TGFA from the cell surface (By similarity). Negatively regulates Wnt signaling, possibly by antagonizing the recruitment of AXIN1 to LRP6 (By similarity).|||Widely expressed (at protein level).|||cytosol http://togogenome.org/gene/10090:Fam162b ^@ http://purl.uniprot.org/uniprot/B2RV81|||http://purl.uniprot.org/uniprot/Q9CX19 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UPF0389 family.|||Membrane http://togogenome.org/gene/10090:Sh3bp5 ^@ http://purl.uniprot.org/uniprot/Q9Z131 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SH3BP5 family.|||Cytoplasmic vesicle membrane|||Functions as guanine nucleotide exchange factor (GEF) with specificity for RAB11A and RAB25 (By similarity). Inhibits the auto- and transphosphorylation activity of BTK. Plays a negative regulatory role in BTK-related cytoplasmic signaling in B-cells. May be involved in BCR-induced apoptotic cell death.|||Interacts with BTK (By similarity). Interacts with all isoforms of MAPK8, MAPK9, MAPK10 and MAPK12 (By similarity). Interacts with GDP-bound and nucleotide-free forms of RAB11A (PubMed:26506309).|||Mitochondrion|||The N-terminal half of the protein mediates interaction with RAB11A and functions as guanine nucleotide exchange factor. Four long alpha-helices (interrupted by a central kink) assemble into coiled coils, giving rise to a 'V' shape. http://togogenome.org/gene/10090:Mmaa ^@ http://purl.uniprot.org/uniprot/Q8C7H1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.|||Cytoplasm|||GTPase activity is stimulated by MMUT.|||GTPase, binds and hydrolyzes GTP (By similarity). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis (By similarity). Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MMUT) (By similarity). Plays a dual role as both a protectase and a reactivase for MMUT (By similarity). Protects MMUT from progressive inactivation by oxidation by decreasing the rate of the formation of the oxidized inactive cofactor hydroxocobalamin (OH2Cbl) (By similarity). Additionally acts a reactivase by promoting the replacement of OH2Cbl by the active cofactor AdoCbl, restoring the activity of MMUT in the presence and hydrolysis of GTP (By similarity).|||Homodimer. Interacts with MMUT (the apoenzyme form); the interaction is GTP dependent.|||Mitochondrion http://togogenome.org/gene/10090:Vmn1r23 ^@ http://purl.uniprot.org/uniprot/Q8R2D0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam151a ^@ http://purl.uniprot.org/uniprot/Q8QZW3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM151 family.|||Membrane http://togogenome.org/gene/10090:Brms1 ^@ http://purl.uniprot.org/uniprot/Q547N0|||http://purl.uniprot.org/uniprot/Q99N20 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BRMS1 family.|||Contains an N-terminal anti-parallel coiled coil formed by two BRMS1 chains; this region can form homohexamers.|||Cytoplasm|||Homohexamer (Potential). Interacts with SNX6, HDAC1 and RELA. Interacts with ARID4A. Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, SUDS3, ARID4A, HDAC1 and HDAC2. Interacts with SPOP; this recruits the protein to a ubiquitin ligase complex containing SPOP and CUL3 (By similarity).|||Nucleus|||Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis (By similarity).|||Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing SPOP, leading to proteasomal degradation. http://togogenome.org/gene/10090:Aldh1a1 ^@ http://purl.uniprot.org/uniprot/P24549 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:12851412). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (PubMed:12851412). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (Probable). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:17567582). Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (By similarity). Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (PubMed:26430123).|||Expressed in retina (PubMed:1935685). Expressed in lens and cornea (at protein level) (PubMed:17567582). Expressed by midbrain dopamine neurons (PubMed:26430123).|||Homotetramer (By similarity). Interacts with PRMT3; the interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity and is independent of the methyltransferase activity of PRMT3 (By similarity).|||Mice lacking Aldh1a1, obtained at the expected Mendelian ratio, are viable and fertile without obvious defects in growth or survival (PubMed:12851412). However, they are more sensitive to retinol toxicity and are less efficient at metabolizing excess retinol to retinoic acid/RA (PubMed:12851412). An excess of retinol leads to the accumulation of retinaldehyde in these mice (PubMed:12851412). Enhanced alcohol consumption and preference is also observed in knockout mice (PubMed:26430123). A consistent lenticular opacification is also detected in old mice (PubMed:17567582).|||The N-terminus is blocked most probably by acetylation.|||The aminobutyraldehyde dehydrogenase activity is negatively regulated by ethanol in vivo.|||axon|||cytosol http://togogenome.org/gene/10090:Eef1e1 ^@ http://purl.uniprot.org/uniprot/Q9D1M4 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By DNA damaging agents, such as UV, adriamycin, actinomycin D and cisplatin.|||Cytoplasm|||Nucleus|||Part of a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:12060739). Can interact simultaneously with MARS1 and EPRS1. Forms a linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit complex. Interacts with ATM and ATR. The interaction with ATM, which takes place independently of TP53, is induced by DNA damage that may occur during genotoxic stress or cell growth. The interaction with ATR is enhanced by UV irradiation (By similarity).|||Positive modulator of ATM response to DNA damage. http://togogenome.org/gene/10090:Tex24 ^@ http://purl.uniprot.org/uniprot/Q5DP50 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected in testis from postnatal day 20 onwards.|||Nuclear factor which might have a role in spermatogenesis.|||Nucleus|||Specific to testis, where it is expressed in spermatogonia. http://togogenome.org/gene/10090:Tpd52l2 ^@ http://purl.uniprot.org/uniprot/Q3TAI4|||http://purl.uniprot.org/uniprot/Q3TUJ9|||http://purl.uniprot.org/uniprot/Q8BKP1|||http://purl.uniprot.org/uniprot/Q9CYZ2 ^@ Similarity|||Subunit ^@ Belongs to the TPD52 family.|||Forms a homodimer or heterodimer with other members of the family. Interacts with MAL2 (By similarity). http://togogenome.org/gene/10090:Mink1 ^@ http://purl.uniprot.org/uniprot/Q9JM52 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Appears to be ubiquitous, expressed in all tissue types examined. Highly expressed in the brain, moderately expressed in kidney and spleen, low levels present in heart and skeletal muscle. Isoform 2 is more abundant in the brain than isoform 1.|||Autophosphorylated.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Interacts with RAP2A and TANC1 (By similarity). Interacts with NCK1.|||Postsynaptic density|||Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1.|||Up-regulated during postnatal brain development.|||axon|||dendrite http://togogenome.org/gene/10090:Nanog ^@ http://purl.uniprot.org/uniprot/A2RS90|||http://purl.uniprot.org/uniprot/B7ZN41|||http://purl.uniprot.org/uniprot/Q80Z64 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Nanog' is derived from 'Tir nan Og' the mythologic Celtic land of the ever young.|||Belongs to the Nanog homeobox family.|||By the transcription factor POU5F1 in ES cells that acts as a direct biphasic regulator: a steady-state concentration of POU5F1 up-regulated its expression, while an elevated concentration of POU5F1 down-regulated its expression. Up-regulated by the transcription factor FOXD3. Up-regulated in ES cells by transcription factors T (Brachyury) and STAT3. Down-regulated by p53 in response to DNA damage induced by ultraviolet light (UV) or doxorubicin. Down-regulated upon ES differentiation by mediating autorepression through interaction with ZNF281/ZFP281.|||Expressed in the central portion of the morula, the inner cell mass (ICM) of the blastocyst, in embryonic stem (ES) and embryonic germ (EG) cells, in the epiblast between 6.5 and 7.5 dpc, in primordial germ cells (PGCs) between 7.75 and 12.5 dpc (at protein level). The expression in PGCs decreases in female germ cells that entered meiosis at 13.5 dpc and in male germ cells that entered mitotic arrest at 14.5 dpc (at protein level). Not expressed in unfertilized eggs or 2- or 8-cell-stage embryos (at protein level). Expressed in the central portion of the morula, the inner cell mass (ICM) of the blastocyst, in ES and EG cells, in the epiblast at 6 dpc and in PGCs of genital ridges between 11.5 and 12.5 dpc. Expression decreases with ES differentiation.|||Interacts with SMAD1 (PubMed:16801560). Interacts with SALL4 (PubMed:16840789). Interacts with ZNF281/ZFP281 (PubMed:21915945, PubMed:22988117). Interacts with PCGF1 (By similarity). Interacts with ESRRB; reciprocally modulates their transcriptional activities (PubMed:18957414). Interacts with NSD2 (PubMed:19483677).|||Loss of pluripotency in both ICM and ES cells and differentiated into extraembryonic (parietal and visceral) endoderm lineage.|||Not expressed in oocytes and spermatogonia (at protein level). Not expressed in many somatic organs, ovary, testis, fibroblast and hematopoietic cell lines.|||Nucleus|||Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal (PubMed:25825768). Imposes pluripotency on ES cells and prevents their differentiation towards extraembryonic endoderm and trophectoderm lineages. Blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes. Acts as a transcriptional activator or repressor. Binds optimally to the DNA consensus sequence 5'-TAAT[GT][GT]-3' or 5'-[CG][GA][CG]C[GC]ATTAN[GC]-3'. Binds to the POU5F1/OCT4 promoter (By similarity). Able to autorepress its expression in differentiating (ES) cells: binds to its own promoter following interaction with ZNF281/ZFP281, leading to recruitment of the NuRD complex and subsequent repression of expression. When overexpressed, promotes cells to enter into S phase and proliferation. http://togogenome.org/gene/10090:Impg1 ^@ http://purl.uniprot.org/uniprot/Q8R1W8 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in the retina (at protein level).|||Chondroitin sulfate-, heparin- and hyaluronan-binding protein (By similarity). May serve to form a basic macromolecular scaffold comprising the insoluble interphotoreceptor matrix (By similarity).|||Highly glycosylated (N- and O-linked carbohydrates and sialic acid).|||Photoreceptor inner segment|||interphotoreceptor matrix|||photoreceptor outer segment http://togogenome.org/gene/10090:Ipo13 ^@ http://purl.uniprot.org/uniprot/Q8K0C1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the importin beta family.|||Cytoplasm|||Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13 (By similarity).|||Interacts with UBC9, RAN, RBM8A, eIF-1A and PAX6.|||Nucleus http://togogenome.org/gene/10090:Vmn1r229 ^@ http://purl.uniprot.org/uniprot/Q8R2A9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Il16 ^@ http://purl.uniprot.org/uniprot/O54824 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Homotetramer (Probable). Isoform 2 interacts with GRIN2A. Isoform 1 interacts with GRIN2D, KCNJ10, KCNJ15 and CACNA1C. Isoform 2 interacts (via PDZ 3 domain) with PPP1R12A, PPP1R12B and PPP1R12C. Isoform 1 interacts with PPP1R12B. Isoform 3 interacts with GABPB1. Isoform 2 interacts (via PDZ 3 domain) with HDAC3 (By similarity).|||Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4.|||Isoform 1 is expressed in neurons of the cerebellum and hippocampus. Isoform 2 is expressed in thymus, spleen and lung.|||Isoform 1 may act as a scaffolding protein that anchors ion channels in the membrane.|||Isoform 2 is involved in cell cycle progression in T-cells. Appears to be involved in transcriptional regulation of SKP2 and is probably part of a transcriptional repression complex on the core promoter of the SKP2 gene. May act as a scaffold for GABPB1 (the DNA-binding subunit the GABP transcription factor complex) and HDAC3 thus maintaining transcriptional repression and blocking cell cycle progression in resting T-cells.|||Nucleus|||Produced by alternative promoter usage. Is probably proteolytically processed to yield IL-16.|||Produced by alternative promoter usage. Is proteolytically processed to yield IL-16.|||Secreted|||Synthesized as a chemo-attractant inactive precursor which is proteolytically cleaved by caspase-3 to yield IL-16. http://togogenome.org/gene/10090:Ckap4 ^@ http://purl.uniprot.org/uniprot/Q8BMK4 ^@ Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contaminating sequence. Vector contamination at the N-terminus.|||Endoplasmic reticulum membrane|||Expressed in cardiomyocytes (at protein level).|||High-affinity epithelial cell surface receptor for APF.|||Increased phosphorylation during mitosis prevents binding to microtubules.|||Interacts with REEP5.|||Mediates the anchoring of the endoplasmic reticulum to microtubules.|||Reversibly palmitoylated. Palmitoylation at Cys-79 by DHHC2 is required for its trafficking from the ER to the plasma membrane and for its perinuclear localization (By similarity).|||cytoskeleton|||perinuclear region http://togogenome.org/gene/10090:Top1 ^@ http://purl.uniprot.org/uniprot/Q04750 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type IB topoisomerase family.|||Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.|||Monomer (By similarity). Interacts with ERCC6 (By similarity).|||Phosphorylation at Ser-508 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.|||Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter.|||Sumoylated. Lys-119 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Rnf168 ^@ http://purl.uniprot.org/uniprot/E9PYW4|||http://purl.uniprot.org/uniprot/Q80XJ2 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ According to a well-established model, RNF168 cannot initiate H2A 'Lys-63'-linked ubiquitination and is recruited following RNF8-dependent histone ubiquitination to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidence is however required to confirm these data.|||According to a well-established model, RNF168 cannot initiate H2A 'Lys-63'-linked ubiquitination and is recruited following RNF8-dependent histone ubiquitination to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidences are however required to confirm these data.|||Belongs to the RNF168 family.|||E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).|||Monomer. Interacts with UBE2N/UBC13.|||Nucleus|||Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs).|||The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs).|||Ubiquitinated. http://togogenome.org/gene/10090:Klhl25 ^@ http://purl.uniprot.org/uniprot/Q8R2P1 ^@ Function|||Subunit ^@ Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL25 and RBX1.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex involved in various processes, such as translation homeostasis and lipid synthesis (PubMed:22578813, PubMed:34491895). The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated EIF4EBP1 (4E-BP1): ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low (PubMed:22578813). The BCR(KLHL25) complex does not target EIF4EBP1 (4E-BP1) when it is hyperphosphorylated or associated with eIF4E (PubMed:22578813). The BCR(KLHL25) complex also acts as a regulator of lipid synthesis by mediating ubiquitination and degradation of ACLY, thereby inhibiting lipid synthesis (PubMed:34491895). BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (PubMed:34491895). http://togogenome.org/gene/10090:Plpp3 ^@ http://purl.uniprot.org/uniprot/Q99JY8 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the PA-phosphatase related phosphoesterase family.|||Cell membrane|||Detected in lung, cerebellum and heart atrium.|||Display a characteristic dynamic and changing pattern of expression throughout the life cycle of the mouse (PubMed:12925589). Expression during early stages of development is specific of structures where multiple inductive interactions occur such as the limb buds, mammary gland primordia, heart cushions and valves among others (PubMed:19123136). Detected in a few cells of the extra-embryonic ectoderm of 6.5 dpc embryos. By 7.5 dpc, starts to be strongly expressed in the anterior visceral endoderm, as well as in the extra-embryonic membranes. By 8.0 dpc, expression extends to a highly localized region around the node and appears at the tip of the allantois. At 8.5 dpc, predominantly expressed in the allantois, the developing gut, the pericardio-peritoneal canal and somites. In 9.5 dpc embryos, persists in the umbilical cord, and is also found in the chorionic region. In later mid-gestation embryos, present at high levels in the apical ectodermal ridge and mesenchyme of the limb buds, in the peripheral nervous system, cranial nerves, and mammary gland primordia (PubMed:12925589).|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Forms functional homodimers and homooligomers that are not required for substrate recognition and catalytic activity. Can also form heterooligomers with other PLPP2 and PLPP3. Interacts with CTNND1; negatively regulates the PLPP3-mediated stabilization of beta-catenin/CTNNB1.|||Golgi apparatus membrane|||Independently of this phosphatase activity may also function in the Wnt signaling pathway and the stabilization of beta-catenin/CTNNB1, thereby regulating cell proliferation, migration and differentiation in angiogenesis or yet in tumor growth (PubMed:12925589, PubMed:27125875). Also plays a role in integrin-mediated cell-cell adhesion in angiogenesis (PubMed:16099422).|||Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound. Has both an extracellular and an intracellular phosphatase activity, allowing the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes. Through the dephosphorylation of extracellular sphingosine-1-phosphate and the regulation of its extra- and intracellular availability, plays a role in vascular homeostasis, regulating endothelial cell migration, adhesion, survival, proliferation and the production of pro-inflammatory cytokines (By similarity). By maintaining the appropriate levels of this lipid in the cerebellum, also ensure its proper development and function (PubMed:21319224). Through its intracellular lipid phosphatase activity may act in early compartments of the secretory pathway, regulating the formation of Golgi to endoplasmic reticulum retrograde transport carriers (By similarity).|||Magnesium-independent phospholipid phosphatase. Insensitive to N-ethylmaleimide.|||Membrane raft|||N-glycosylated. Contains high-mannose oligosaccharides.|||The dityrosine basolateral targeting motif mediates localization to the basolateral membrane in polarized cells.|||The homozygous knockout of Plpp3 is embryonic lethal (PubMed:12925589, PubMed:17610274, PubMed:19123136). It is characterized by a delay in development, absence of chorioallantoic fusion at the 6 somite stage, allantois compaction, impaired remodeling of the primary capillary plexus of the yolk sac and gastrulation defects with low penetrance. Persistence of open neural tube is also frequently observed (PubMed:12925589, PubMed:19123136). Conditional knockout of Plpp3 in the cerebellum is associated with defects in postnatal cerebellum development, modifications in the cytoarchitecture and arrangement of Bergmann glia with a mild non-progressive motor coordination defect (PubMed:21319224). Conditional knockout of Plpp3 in endothelial cells is associated with vascular leakage and hemorrhage that likely result in insufficient cardiovascular development and the observed embryonic lethality (PubMed:27125875). Conditional knockout of Plpp3 in adipocytes does not affect the development of the adipose tissue. However, mutant homozygous mice display lower accumulation of ceramide and sphingomyelin on high fat or Western diets compared to control animals (PubMed:29889835).|||The integrin-binding motif mediates the binding to integrin alpha-5/beta-1 (ITGA5:ITGB1) and integrin alpha-V/beta-3 (ITGAV:ITGB3) and is required for the function in integrin-mediated cell-cell adhesion.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Fen1 ^@ http://purl.uniprot.org/uniprot/Q8C952|||http://purl.uniprot.org/uniprot/Q91Z50 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.|||Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.|||Mitochondrion|||Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Atg9b ^@ http://purl.uniprot.org/uniprot/Q6EBV9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATG9 family.|||Expressed in heart, brain, and placenta and testis.|||Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9B-containing vesicles, thereby enabling growth into autophagosomes.|||Homotrimer; forms a homotrimer with a central pore that forms a path between the two membrane leaflets.|||Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:15755735). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome. Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion (By similarity). In addition to autophagy, also plays a role in necrotic cell death (By similarity).|||Preautophagosomal structure membrane|||The tyrosine-based sorting signal motif, also named YXX-psi motif, promotes interaction with the AP-4 complex. http://togogenome.org/gene/10090:Fmnl1 ^@ http://purl.uniprot.org/uniprot/A2AB60|||http://purl.uniprot.org/uniprot/Q3TY82|||http://purl.uniprot.org/uniprot/Q9JL26 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the formin homology family.|||Cell membrane|||Cytoplasm|||Highly expressed in the spleen, lymph node and bone marrow cells.|||Interacts with RAC1, PFN1 and PFN2. Interacts (activated by RAC1) with SRGAP2 (via SH3 domain); regulates the actin filament severing activity of FMNL1.|||Myristoylation mediates membrane localization.|||Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape. May play a role in the control of cell motility and survival of macrophages.|||The DAD domain regulates activation via by an autoinhibitory interaction with the N-terminus. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).|||phagosome http://togogenome.org/gene/10090:Adam1b ^@ http://purl.uniprot.org/uniprot/Q8R534 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expression is detected 20 days after birth and increases gradually up to day 60.|||Heterodimer with ADAM2/fertilin subunit beta.|||May play a role in spermatogenesis and sperm maturation.|||Membrane|||Testis. http://togogenome.org/gene/10090:Or4b12 ^@ http://purl.uniprot.org/uniprot/Q8VG62 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:7420426K07Rik ^@ http://purl.uniprot.org/uniprot/Q3UX66 ^@ Similarity ^@ Belongs to the PRR23 family. http://togogenome.org/gene/10090:Mob3c ^@ http://purl.uniprot.org/uniprot/Q8BJG4 ^@ Function|||Similarity ^@ Belongs to the MOB1/phocein family.|||May regulate the activity of kinases. http://togogenome.org/gene/10090:Or4f59 ^@ http://purl.uniprot.org/uniprot/Q8VF10 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grin2a ^@ http://purl.uniprot.org/uniprot/P35436 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.|||Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A subfamily.|||Cell membrane|||Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium (PubMed:1374164). Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have lower sensitivity to glutamate and faster deactivation kinetics than channels formed by GRIN1 and GRIN2B (By similarity). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (PubMed:7816096, PubMed:8987814).|||Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand-binding domains triggers channel gating.|||Cytoplasmic vesicle membrane|||Detected in striatum (PubMed:28469074). Detected in forbrain (PubMed:7816096). Detected in cerebellum (at protein level) (PubMed:8987814). Detected in brain cortex, piriform cortex, hippocampus, caudate-putamen, dentate gyrus and granule cell layer (PubMed:1374164, PubMed:7816096).|||Heterotetramer (By similarity). Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1374164). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (PubMed:12008020). In vivo, the subunit composition may depend on the expression levels of the different subunits. Found in a complex with GRIN1, GRIN3A and PPP2CB (By similarity). Found in a complex with GRIN1 and GRIN3B (PubMed:12008020). Interacts with AIP1 (By similarity). Interacts with HIP1 and NETO1 (PubMed:17329427, PubMed:19243221). Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (PubMed:23524343). Interacts with PDZ domains of PATJ and DLG4. Interacts with LRFN2 (By similarity). Interacts with RPH3A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity). Interacts with SORCS2 (PubMed:28469074). Interacts with ARC; preventing ARC oligomerization (By similarity).|||Mutant mice appear grossly normal and are fertile (PubMed:7816096, PubMed:8987814). NMDA channel currents are decreased in mutant brain slices. Contrary to wild-type, where tetanic stimulation leads to a strong long-term increase in synaptic strength, only modest long-term synaptic potentiation is seen in mutant mice (PubMed:7816096). Mossy fiber granule cells from mutant mice present a decrease of the slow component of the excitatory postsynaptic current (PubMed:8987814). The slow component of the excitatory postsynaptic current is nearly abolished in mossy fiber cells from mice lacking both Grin2a and Grin2c (PubMed:8987814). Mutant mice present subtle deficits in spatial learning (PubMed:7816096). Mice lacking both Grin2a and Grin2c display subtle motor deficits; they have no visible phenotype when performing simple tasks, but have decreased ability to walk across a narrow wooden bar, and are unable to stay on a rapidly rotating rod (PubMed:8987814).|||Postsynaptic cell membrane|||Synapse|||dendritic spine http://togogenome.org/gene/10090:Mmp24 ^@ http://purl.uniprot.org/uniprot/Q9R0S2 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Cleaved by a furin endopeptidase in the trans-Golgi network.|||Expressed at day 11 until day 15, before dropping around day 17 before birth. Expressed in the cerebrum in embryos, but it declines after birth, while expression in the cerebellum starts to increase postnatally and continues thereafter.|||Interacts with GRIP1 and GRIP2 (By similarity). Interacts (via PDZ-binding motif) with APBA3 (via PDZ domain).|||Mainly expressed in neuronal cells of both central and peripheral nervous systems. Expressed by CGRP-containing peptidergic nociceptors in dorsal root ganglia (PubMed:19805319). Expressed in adult neural stem cell and ependymocytes (PubMed:24952463). Expressed at low level in testis.|||Metalloprotease that mediates cleavage of N-cadherin (CDH2) and acts as a regulator of neuro-immune interactions and neural stem cell quiescence (PubMed:19805319, PubMed:24952463). Involved in cell-cell interactions between nociceptive neurites and mast cells, possibly by mediating cleavage of CDH2, thereby acting as a mediator of peripheral thermal nociception and inflammatory hyperalgesia (PubMed:19805319). Key regulator of neural stem cells quiescence by mediating cleavage of CDH2, affecting CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate their quiescence (PubMed:24952463). May play a role in axonal growth (PubMed:11714638). Able to activate progelatinase A. May also be a proteoglycanase involved in degradation of proteoglycans, such as dermatan sulfate and chondroitin sulfate proteoglycans. Cleaves partially fibronectin, but not collagen type I, nor laminin (PubMed:10622708).|||No visible phenotype. Mice are viable, develop normally and are fertile. They however display enhanced sensitivity to noxious thermal stimuli under basal conditions characterized by an absence of thermal inflammatory hyperalgesia (PubMed:19805319). In subependymal zone, more intense signal is observed for extracellular N-cadherin (Cdh2) as well as increased levels of full-length Cdh2 without changes in Cdh2 messenger RNA levels (PubMed:24952463).|||The PDZ-binding motif (also named EWV motif) is required for interaction with PDZ domains of APBA3 and recycling through the trans-Golgi network.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix|||trans-Golgi network membrane http://togogenome.org/gene/10090:Fam171b ^@ http://purl.uniprot.org/uniprot/Q14CH0 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAM171 family.|||Cytoplasmic granule|||Expressed in the brain, predominantly in the thalamus, in the hippocampal formation (in CA1, CA2 and CA3 regions and in the dentate gyrus), in the cerebellum (in Purkinje and granule cell layers, as well as neurons of the deep cerebellar nuclei) and cerebral cortex (at protein level) (PubMed:34052262). Expressed predominantly in neurons (PubMed:34052262).|||Membrane http://togogenome.org/gene/10090:Tial1 ^@ http://purl.uniprot.org/uniprot/P70318 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytolytic granule|||Cytoplasm|||Expressed both in primordial germ cells (PGCs) and in neighboring somatic cells.|||Interacts with FASTK.|||Nucleus|||Phosphorylated by MAPK14 following DNA damage, releasing TIAR from GADD45A mRNA.|||RNA-binding protein involved in alternative pre-RNA splicing and in cytoplasmic stress granules formation (By similarity). Shows a preference for uridine-rich RNAs (By similarity). Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIA1 mRNA (PubMed:11514562). Promotes the inclusion of TIA1 exon 5 to give rise to the long isoform (isoform a) of TIA1 (PubMed:17488725). Acts downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SG) (By similarity). Possesses nucleolytic activity against cytotoxic lymphocyte target cells (By similarity). May be involved in apoptosis (By similarity).|||Stress granule|||The RRM 2 domain is required for the binding to target RNA, and the RRM 1 and RRM 3 domains seem to contribute to the affinity of the interaction with RNA.|||The RRM2 domain and the C-terminal residues 290-339 contribute to nuclear localization.|||The RRM3 domain mediates nuclear export and cytoplasmic localization in a manner dependent on RNA- binding. http://togogenome.org/gene/10090:Mpp2 ^@ http://purl.uniprot.org/uniprot/Q9WV34 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAGUK family.|||Can homomultimerise. Interacts with CACNG2. Interacts (via the SH3-Guanylate kinase-like sub-module) with DLG4/PSD95 and DLGAP1/GKAP. Interacts (via the PDZ domain) with CADM1 (via C-terminus) (By similarity). Interacts with KCNN2/SK2 (via N-terminal domain) (PubMed:26880549). Interacts with SRC (By similarity).|||Expressed in pyramidal neurons of CA1 region of the hippocampus.|||Membrane|||Phosphorylated by SRC.|||Postsynaptic MAGUK scaffold protein that links CADM1 cell adhesion molecules to core components of the postsynaptic density (By similarity). In CA1 pyramidal neurons, required for synaptic KCNN2-containing channel function and long-term potentiation expression (PubMed:26880549). Seems to negatively regulate SRC function in epithelial cells (By similarity).|||Postsynaptic density|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Ralb ^@ http://purl.uniprot.org/uniprot/Q9JIW9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Interacts with EXOC2/Sec5 and EXOC8/Exo84 (By similarity). Interacts (via effector domain) with RALBP1 (By similarity).|||Midbody|||Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles (By similarity). Required both to stabilize the assembly of the exocyst complex and to localize functional exocyst complexes to the leading edge of migrating cells (By similarity). Required for suppression of apoptosis (By similarity). In late stages of cytokinesis, upon completion of the bridge formation between dividing cells, mediates exocyst recruitment to the midbody to drive abscission (By similarity). Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors (By similarity).|||Prenylation is essential for membrane localization.|||The farnesylated form confers resistance to the proapoptotic and anti-anchorage-dependent growth effects of some geranylgeranyltransferase I inhibitors. http://togogenome.org/gene/10090:Sms ^@ http://purl.uniprot.org/uniprot/P97355 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the spermidine/spermine synthase family.|||Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM) (PubMed:9467015). Required for normal viability, growth and fertility (PubMed:15459188).|||Composed of 3 domains: the N-terminal domain has structural similarity to S-adenosylmethionine decarboxylase, the central domain is made up of four beta strands and the C-terminal domain is similar in structure to spermidine synthase. The N- and C-terminal domains are both required for activity.|||Homodimer. Dimerization is mediated through the N-terminal domain and seems to be required for activity as deletion of the N-terminal domain causes complete loss of activity.|||Mouse ES cells lacking Sms display normal growth rates but are sensitive to antiproliferative and DNA damage-inducing drugs. http://togogenome.org/gene/10090:Or14a260 ^@ http://purl.uniprot.org/uniprot/Q8VFN8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fhl1 ^@ http://purl.uniprot.org/uniprot/P97447 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Isoform 1 seems to be most abundant in each tissue and isoform 2 much less abundant. Isoform 1 is highly expressed in skeletal muscle and lung, and to a lesser extent in heart, brain and kidney. Isoform 2 was found in brain, lung kidney and genital organs.|||May have an involvement in muscle development or hypertrophy. Isoform 2 binds to RBP-J and plays a negative regulatory role in the RBP-J-mediated transcription in mammalian systems.|||Nucleus http://togogenome.org/gene/10090:Cyp3a16 ^@ http://purl.uniprot.org/uniprot/Q2KHL4|||http://purl.uniprot.org/uniprot/Q64481 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Fetal- and puberty-specific.|||Membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens. http://togogenome.org/gene/10090:Aldoart1 ^@ http://purl.uniprot.org/uniprot/A6ZI46 ^@ Similarity ^@ Belongs to the class I fructose-bisphosphate aldolase family. http://togogenome.org/gene/10090:Qser1 ^@ http://purl.uniprot.org/uniprot/A0A338P6K9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Interacts with TET1.|||Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation. http://togogenome.org/gene/10090:Itpr2 ^@ http://purl.uniprot.org/uniprot/Q9Z329 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the InsP3 receptor family.|||Endoplasmic reticulum membrane|||Homotetramer. Interacts with CABP1. Interacts with BOK; regulates ITPR2 expression. Interacts with BCL2L10 (By similarity). Interacts with TRPC4 (By similarity).|||Isoform 3 has neither inositol 1,4,5-trisphosphate binding activity nor calcium releasing activity.|||Isoforms 1 and 3 are widely expressed. Isoform 2 is found in skeletal muscle and heart.|||Phosphorylation by cAMP-dependent PKA on Ser-937 increases calcium release.|||Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA.|||The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.|||There is a 3-fold reduction in the number of pilocarpine-responsive sweat glands in knockout animals. The sweat glands of these animals show a significant reduction in Ca(2+) response following acetylcholine stimulation compared with those of wild-type animals. The Itpr2-null animals retained some residual sweat production, in contrast to the human phenotype of anhidrosis. This phenotypic discrepancy may be due to differences between humans and mice in the expression of the 3 ITPR isoforms, as well as to the different stimuli used to provoke sweat production in Itpr2-null animals. http://togogenome.org/gene/10090:Prss48 ^@ http://purl.uniprot.org/uniprot/Q14B25 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Secreted http://togogenome.org/gene/10090:Or4k36 ^@ http://purl.uniprot.org/uniprot/Q8VGG8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lactbl1 ^@ http://purl.uniprot.org/uniprot/S4R213 ^@ Subcellular Location Annotation ^@ Mitochondrion http://togogenome.org/gene/10090:Hdgfl3 ^@ http://purl.uniprot.org/uniprot/Q9JMG7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HDGF family.|||Enhances DNA synthesis and may play a role in cell proliferation.|||Nucleus http://togogenome.org/gene/10090:Dap3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1B9|||http://purl.uniprot.org/uniprot/G3X9M0|||http://purl.uniprot.org/uniprot/Q9ER88 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS29 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins. Interacts with DELE1. Interacts with NOA1.|||Involved in mediating interferon-gamma-induced cell death.|||Mitochondrion http://togogenome.org/gene/10090:Lce3a ^@ http://purl.uniprot.org/uniprot/Q497I5 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Lactb2 ^@ http://purl.uniprot.org/uniprot/Q99KR3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||Binds 2 Zn(2+) ions per subunit.|||Endoribonuclease; cleaves preferentially 3' to purine-pyrimidine dinucleotide motifs in single-stranded RNA. The cleavage product contains a free 3' -OH group. Has no activity with double-stranded RNA or DNA. Required for normal mitochondrial function and cell viability.|||Mitochondrion matrix|||Monomer. http://togogenome.org/gene/10090:Or6c215 ^@ http://purl.uniprot.org/uniprot/Q8VFI1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adck5 ^@ http://purl.uniprot.org/uniprot/E9PUK2|||http://purl.uniprot.org/uniprot/Q80V03 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. ADCK protein kinase family.|||Intron retention.|||Membrane|||The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr). http://togogenome.org/gene/10090:Cacul1 ^@ http://purl.uniprot.org/uniprot/E9PV69|||http://purl.uniprot.org/uniprot/Q3TAW5|||http://purl.uniprot.org/uniprot/Q8R0X2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the cullin family.|||Cell cycle associated protein capable of promoting cell proliferation through the activation of CDK2 at the G1/S phase transition.|||Interacts with CDK2. http://togogenome.org/gene/10090:Ykt6 ^@ http://purl.uniprot.org/uniprot/Q9CQW1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synaptobrevin family.|||Cytoplasmic vesicle membrane|||Farnesylation is required for Golgi targeting.|||Golgi apparatus membrane|||Identified in 2 different SNARE complexes; the first one composed of GOSR1, GOSR2 and STX5 and the second one composed of BET1L, GOSR1 and STX5.|||Palmitoylated; catalyzes its own palmitoylation. Palmitoylation is required for Golgi targeting.|||The longin domain regulates palmitoylation and membrane targeting.|||Vesicular soluble NSF attachment protein receptor (v-SNARE) mediating vesicle docking and fusion to a specific acceptor cellular compartment. Functions in endoplasmic reticulum to Golgi transport; as part of a SNARE complex composed of GOSR1, GOSR2 and STX5. Functions in early/recycling endosome to TGN transport; as part of a SNARE complex composed of BET1L, GOSR1 and STX5. Has a S-palmitoyl transferase activity.|||cytosol http://togogenome.org/gene/10090:Or4k49 ^@ http://purl.uniprot.org/uniprot/Q7TQX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpx2 ^@ http://purl.uniprot.org/uniprot/Q9JHC0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glutathione peroxidase family.|||Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides. Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors.|||Homotetramer.|||cytosol http://togogenome.org/gene/10090:Gtf2i ^@ http://purl.uniprot.org/uniprot/Q3UHU8|||http://purl.uniprot.org/uniprot/Q9ESZ8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TFII-I family.|||Cytoplasm|||Homodimer (Potential). Interacts with SRF and PHOX1. Binds a pyrimidine-rich initiator (Inr) and a recognition site (E-box) for upstream stimulatory factor 1 (USF1). Associates with the PH domain of Bruton's tyrosine kinase (BTK) (By similarity). May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with BTK and ARID3A. Interacts with isoform beta of PRKG1 (By similarity).|||Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C-FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box (By similarity). Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation.|||Nucleus|||Sumoylated.|||Transiently phosphorylated on tyrosine residues by BTK in response to B-cell receptor stimulation. Phosphorylation on Tyr-248 and Tyr-398, and perhaps, on Tyr-503 contributes to BTK-mediated transcriptional activation (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Dhx8 ^@ http://purl.uniprot.org/uniprot/A2A4P0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DEAH subfamily. DDX8/PRP22 sub-subfamily.|||Identified in the spliceosome C complex. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation. Interacts with SRRM2. Interacts with CACTIN.|||Involved in pre-mRNA splicing as component of the spliceosome. Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome.|||Nucleus|||The RS domain confers a nuclear localization signal, and appears to facilitate the interaction with the spliceosome. http://togogenome.org/gene/10090:Atp7a ^@ http://purl.uniprot.org/uniprot/A2AG68|||http://purl.uniprot.org/uniprot/Q64430 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:25639447, PubMed:27337370, PubMed:18650808). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (By similarity). Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway (PubMed:27337370, PubMed:18650808, PubMed:16371425, PubMed:12488345). Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions (By similarity). May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (PubMed:25639447, PubMed:15634787, PubMed:16371425, PubMed:12488345). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (PubMed:18650808).|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.|||Cell membrane|||Cell-specific silencing in motor neurons is associated with loss of motor neuron cell bodies and progressive denervation of the neuromuscular junctions with aging, consistent with the clinical features of human distal spinal muscular atrophy X-linked disease, 3 (DSMAX3).|||Contains three di-leucine motifs in the C-terminus which are required for recycling from the plasma membrane to the TGN. The di-leucine 1478-Leu-Leu-1479 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1458-Leu-Leu-1459 motif is a sorting signal for retrograde trafficking to TGN via early endosomes.|||Defects in Atp7a are associated with mottled, an X-linked recessive condition characterized by mottled pigmentation of the coat, defects in connective tissue and neonatal or fetal death. It is due to a defect in absorption and transport of copper. The mottled mutants exhibit a diversity of phenotypes. Two of these mutants are called brindled and blotchy and their phenotypes resemble classical Menkes disease (MD) and occipital horn syndrome (OHS) in humans, respectively. Other mutants are called dappled, mosaic, tortoiseshell, pewter, etc.|||Detected 10 days after birth in pituitary and adrenal endocrine tissues and at a lower level in hypothalamus and atrium (at protein level).|||Early endosome membrane|||Melanosome membrane|||Membrane|||Monomer. Interacts with PDZD11. Interacts with ATOX1 and COMMD1 (By similarity). Interacts with TYRP1 (PubMed:18650808). Directly interacts with SOD3; this interaction is copper-dependent and is required for SOD3 activity (PubMed:16371425).|||Postsynaptic density|||The ATP binding site comprises residues located in alpha-1 and alpha-2 helices and beta-2 and beta-3 strands, which are involved in van der Waal's interactions, and Glu-1072 which forms an hydrogen bond with the adenine ring.|||The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion via the cysteine residues within the CXXC motif. The transfer of Cu(+) ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu(+)-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu(+) ion.|||Widely expressed (PubMed:25639447, PubMed:8054976, PubMed:12488345). Highly expressed in pituitary endocrine cells (PubMed:12488345). Expressed in melanocytes (at protein level) (PubMed:18650808). Expressed in motor neuron (at protein level) (PubMed:25639447). Expressed in hippocampal neuron (at protein level) (PubMed:15634787). In the kidney, it is detected in the proximal and distal tubules (at protein level) (PubMed:9215672). Expressed in aorta (at protein level) (PubMed:16371425).|||axon|||dendrite|||trans-Golgi network membrane http://togogenome.org/gene/10090:Pip5k1a ^@ http://purl.uniprot.org/uniprot/P70182 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphatidic acid.|||Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:8798574, PubMed:9535851). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (By similarity). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (PubMed:18772378). Can also use phosphatidylinositol (PtdIns) as substrate in vitro (By similarity). Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (PubMed:19153220). Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup (PubMed:19153220). Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion (PubMed:18772378). Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, IP3 and DAG, that will mobilize internal calcium and drive keratinocyte differentiation (By similarity). Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes (PubMed:27739494). Together with PIP5K1C has a role during embryogenesis (PubMed:20622009). Independently of its catalytic activity, is required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of the small GTPase RAC1 to the plasma membrane (PubMed:10679324). Also functions in the nucleus where it acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs (By similarity).|||Cell membrane|||Cytoplasm|||Expression is highest during early embryogenesis and slightly decreases over time.|||Highest expression in brain. Also detected in skeletal muscle, testis, brain and lung.|||Interacts with RAC1 (PubMed:10679324). Interacts with TUT1 (By similarity). Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and CTNND1 at the plasma membrane upon calcium stimulation (By similarity). Found in a ternary complex with IRS1 and DGKZ in the absence of insulin stimulation (PubMed:27739494). Interacts with DGKZ (By similarity). Interacts with PIP4K2C; the interaction inhibits PIP5K1A kinase activity (By similarity).|||Nucleus|||Nucleus speckle|||Survive to adulthood, but bred poorly and display reduced fertility. Failed to form any vessel occlusion after chemical-induced carotid injury. Platelets have defective aggregation. Bone marrow-derived macrophages are defective in actin polymerization during phagocytosis. PIP5K1A and PIP5K1C double mutant mice are embryonic lethal.|||There is confusion in the literature with phosphatidylinositol 4-phosphate 5-kinase type I nomenclature due to the fact that frequently mouse PIP5K1B is named Phosphatidylinositol 4-phosphate 5-kinase type I alpha.|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Nup43 ^@ http://purl.uniprot.org/uniprot/P59235 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13 (By similarity).|||Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation (By similarity).|||kinetochore|||nuclear pore complex http://togogenome.org/gene/10090:Tmem42 ^@ http://purl.uniprot.org/uniprot/Q9CR22 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Hhat ^@ http://purl.uniprot.org/uniprot/Q8BMT9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the membrane-bound acyltransferase family. HHAT subfamily.|||Broadly expressed from 7 dpc. At 10.5 dpc, strongly expressed in anterior ectoderm, pharyngeal arches, and distal part of the limb.|||Conditional knockout embryos are characterized by a smaller size and holoprosencephaly at 10.5 dpc, shortening of limbs at 13.5 dpc, and severe short-limb dwarfism at birth. They die soon after birth. Testicular development is significantly impaired in XY embryos by 12.5 dpc. There is a massive reduction in testis size, a reduction in the number of testis cords which are irregular in shape and diameter, and an almost complete absence of Leydig cells (PubMed:24784881).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Palmitoyl acyltransferase that catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling during limb development (PubMed:15075292). It also catalyzes N-terminal palmitoylation of DHH (By similarity). Promotes the transfer of palmitoyl-CoA from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane, where SHH palmitoylation occurs (By similarity). Plays a role in proper testis cord formation and the differentiation of Leydig cells (PubMed:24784881). http://togogenome.org/gene/10090:Hcrtr1 ^@ http://purl.uniprot.org/uniprot/P58307|||http://purl.uniprot.org/uniprot/Q0VDP6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding.|||The N-terminal region is required for orexin signaling.|||Widely expressed. http://togogenome.org/gene/10090:Tbx21 ^@ http://purl.uniprot.org/uniprot/Q9JKD8 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Induced during early Th1 cell differentiation, gradually decreasing at later stages.|||Interacts with RUNX1 and RUNX3 (PubMed:21151104). Interacts with ITK (PubMed:15662016). The phosphorylated form (at Tyr-525) interacts with GATA3 (PubMed:15662016, PubMed:21690296, PubMed:23616576). Interacts with ABL1 (PubMed:21690296). Interacts with RELA (PubMed:23616576). The phosphorylated form (at Thr-302) interacts with NFATC2 (PubMed:23616576). Interacts with KDM6B (PubMed:21095589). Interacts with SMARCA4 in a KDM6B-dependent manner (PubMed:21095589). Interacts with CCTN1 and CDK9 (PubMed:27292648). Interacts with USP10 (By similarity).|||Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs. Activates transcription of a set of genes important for Th1 cell function, including those encoding IFN-gamma and the chemokine receptor CXCR3. Activates IFNG and CXCR3 genes in part by recruiting chromatin remodeling complexes including KDM6B, a SMARCA4-containing SWI/SNF-complex, and an H3K4me2-methyltransferase complex to their promoters and all of these complexes serve to establish a more permissive chromatin state conducive with transcriptional activation (PubMed:10761931, PubMed:17923685, PubMed:21095589). Can activate Th1 genes also via recruitment of Mediator complex and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1) in the form of the super elongation complex (SEC) to super-enhancers and associated genes in activated Th1 cells (PubMed:27292648). Inhibits the Th17 cell lineage commitment by blocking RUNX1-mediated transactivation of Th17 cell-specific transcriptinal regulator RORC (PubMed:21151104). Inhibits the Th2 cell lineage commitment by suppressing the production of Th2 cytokines, such as IL-4, IL-5, and IL- 13, via repression of transcriptional regulators GATA3 and NFATC2 (PubMed:15662016, PubMed:21690296, PubMed:23616576). Protects Th1 cells from amplifying aberrant type-I IFN response in an IFN-gamma abundant microenvironment by acting as a repressor of type-I IFN transcription factors and type-I IFN- stimulated genes (PubMed:28623086). Acts as a regulator of antiviral B-cell responses; controls chronic viral infection by promoting the antiviral antibody IgG2a isotype switching and via regulation of a broad antiviral gene expression program (PubMed:27430722).|||Nucleus|||Phosphorylations at Ser-52, Tyr-76, Ser-224 and Ser-508 are regulated by mTORC1 (PubMed:28424242). Phosphorylation at Tyr-525 is essential for its interaction GATA3 (PubMed:15662016). Phosphorylation at Tyr-219, Tyr-265 and Tyr-304 enhances its transcriptional activator activity (PubMed:21690296). Phosphorylation at Thr-302 is required for its interaction with NFATC2 (PubMed:23616576).|||T-cell specific (PubMed:10761931, PubMed:11087660). Expressed in regulatory T (TReg) cells (PubMed:28607488).|||Ubiquitinated at Lys-313, leading to its degradation by the proteasome. Ubiquitination is essential for controlling protein stability, binding to the T-box-binding element of the IFN-gamma promoter, and for interaction with NFATC2 through induction of phosphorylation at Thr-302 (PubMed:23616576). Deubiquitinated by USP10 leading to its stabilization (By similarity). http://togogenome.org/gene/10090:Cacng8 ^@ http://purl.uniprot.org/uniprot/S4R2F1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Membrane|||Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. http://togogenome.org/gene/10090:Mnt ^@ http://purl.uniprot.org/uniprot/O08789 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds DNA as a heterodimer with MAX and represses transcription. Binds to the canonical E box sequence 5'-CACGTG-3' and, with higher affinity, to 5'-CACGCG-3'.|||Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer with MAX.|||Nucleus http://togogenome.org/gene/10090:Rflna ^@ http://purl.uniprot.org/uniprot/Q7TS73 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Refilin family.|||Detected in various tissues, with highest expression in lung, followed by spleen.|||Expression is first detected in the marginal zone of the vertebral primordia at 12.5 dpc. Expression is subsequently observed during skeletal development in the cartilaginous elements including the vertebral bodies, carpal bones, femora, ribs and caudal vertebrae. At 18.5 dpc, expression is increased in the layers of proliferating and prehypertrophic chondrocytes. Furthermore, expression is also observed in intervertebral disk, including nucleus pulposus and annulus fibrosus, during skeletal development.|||Interacts with FLNA and FLNB.|||Involved in the regulation of the perinuclear actin network and nuclear shape through interaction with filamins. Plays an essential role in the formation of cartilaginous skeletal elements.|||No visible phenotype; probably due to redundancy with RFLNB. RFLNA and RFLNB double mutant mice exhibit severe skeletal malformations, as characterized by scoliosis, kyphosis, intervertebral disks defects, vertebral fusion in the spine and longitudinal bone growth retardation. Chondrocyte maturation is accelerated in double mutant mice.|||Up-regulated during chondrocyte differentiation.|||cytoskeleton http://togogenome.org/gene/10090:Tmem168 ^@ http://purl.uniprot.org/uniprot/Q91VX9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM168 family.|||Nucleus membrane|||Plays a key role in maintaining the cardiac electrical stability by modulating cell surface expression of SCN5A (PubMed:32175648). Plays a role i the modulation of anxiety behavior by regulating GABAergic neuronal system in the nucleus accumbens (PubMed:29211814). http://togogenome.org/gene/10090:Or5a3 ^@ http://purl.uniprot.org/uniprot/Q8VFV3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpcpd1 ^@ http://purl.uniprot.org/uniprot/Q8C0L9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Down-regulated in skeletal muscles atrophies, including atrophies linked to aging and denervation.|||May be involved in the negative regulation of skeletal muscle differentiation, independently of its glycerophosphocholine phosphodiesterase activity.|||Widely expressed with highest levels in skeletal muscle and heart.|||cytosol http://togogenome.org/gene/10090:Mcfd2 ^@ http://purl.uniprot.org/uniprot/Q8K5B2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Golgi apparatus|||Interacts in a calcium-dependent manner with LMAN1.|||The MCFD2-LMAN1 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins. http://togogenome.org/gene/10090:Cmpk2 ^@ http://purl.uniprot.org/uniprot/Q3U5Q7 ^@ Disruption Phenotype|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the thymidylate kinase family.|||By lipopolysaccharides in macrophages and in primary microglia.|||Deletion mutant mice display calcification deposits in the brain. Neurons show reduced mitochondrial DNA copy number and impaired phosphorus and energy homeostasis, suggesting that dysregulation of mitochondrial function may promote the initiation and progressive development of brain calcification.|||Mitochondrial nucleotide monophosphate kinase needed for salvage dNTP synthesis that mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways. Restricts the replication of multiple viruses including flaviviruses or coronaviruses. Together with viperin/RSAD2 and ddhCTP, suppresses the replication of several coronaviruses through inhibition of the viral RNA-dependent RNA polymerase activities (By similarity). Concerning flaviviruses, restricts RNA translation when localized to the mitochondria independently of its kinase activity (By similarity). Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as phosphate donor. Efficacy is highest for dUMP followed by dCMP while CMP and UMP are poor substrates. Controls therefore mitochondrial DNA synthesis by supplying required deoxyribonucleotides (PubMed:36443312). CMPK2-dependent mitochondrial DNA synthesis is necessary for the production of oxidized mitochondrial DNA fragments after exposure to NLRP3 activators (PubMed:30046112). In turn, cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation (PubMed:30046112).|||Mitochondrion|||Sequence differs due to frameshifts, sequencing errors and other discrepancies.|||Strongly expressed in the brain. http://togogenome.org/gene/10090:Perp ^@ http://purl.uniprot.org/uniprot/Q9JK95 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM47 family.|||Cell membrane|||Component of intercellular desmosome junctions. Plays a role in stratified epithelial integrity and cell-cell adhesion by promoting desmosome assembly. Plays a role as an effector in the TP53-dependent apoptotic pathway.|||Deficient mice exhibit postnatal lethality and defects in stratified epithelia.|||Expressed in developing skin during and after the stratification process from 9.5 to 15.5 dpc (at protein level). Expressed in ectoderm of the developing branchial arches and limb buds from the 9.5 to 10.5 dpc. Expressed in epithelia of the oral mucosa and skin from the 16.5 to 18.5 dpc.|||Expressed in the stratified squamous skin epithelium of the skin and the tongue, but not in simple epithelia (at protein level). Expressed in apoptotic cells.|||Plays a role as an effector in the TP53-dependent apoptotic pathway.|||Up-regulated by UV irradiation, doxorubicin (DOX) and TP53 in embryo fibroblasts.|||desmosome http://togogenome.org/gene/10090:Dnai3 ^@ http://purl.uniprot.org/uniprot/B2RY71 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of cell migration, invasion, and metastasis downstream of p53/TP53, through inhibition of Arp2/3 complex-mediated actin polymerization (By similarity). Via its association with the multisubunit axonemal dynein complex, is potentially involved in the regulation of cilia function (PubMed:30060180). May play a role in osteogenesis of dental tissue-derived mesenchymal stem cells (PubMed:25498833).|||Cytoplasm|||Deficient mice shown no overt abnormalities in body size, development, behavior, or fertility.|||Interacts with ACTR2; this interaction reduces binding of the Arp2/3 complex to the VCA domain of nucleation promoting factors (By similarity). Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains (PubMed:30060180). Found in a associated with the catalytic heavy chain DNAH2, the intermediate chain DNAI4, and the light chain DYNLT1 (PubMed:30060180).|||Strongly expressed in the testes (PubMed:26501274). Detected also in brain and lung tissues (PubMed:26501274). http://togogenome.org/gene/10090:Gdf9 ^@ http://purl.uniprot.org/uniprot/Q07105|||http://purl.uniprot.org/uniprot/Q3UWR9|||http://purl.uniprot.org/uniprot/Q7TPZ4 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.|||Ovarian physiology and fertility are controlled by endocrine and paracrine signals. These act in a species-dependent manner and determine the ovulation quota in different mammalian species. While humans, and mammals such as the cow or red deer, normally ovulate only one egg per cycle, other mammals such as mouse and pig can ovulate in excess of ten per cycle. The mechanisms that regulate the species-specific differences in the number of follicles that go onto ovulate during each reproductive cycle are poorly understood. According to PubMed:21970812, mRNA expression levels of GDF9 and BMP15 are tightly coregulated within each species and influence species-specific ovulation-rates.|||Ovary. Strongly expressed in germinal vesicle (GV) stage oocytes, MII-stage oocytes and in zygotes (PubMed:24357321).|||Phosphorylated; phosphorylation is critical for GDF9 function.|||Required for ovarian folliculogenesis.|||Secreted http://togogenome.org/gene/10090:Or12j4 ^@ http://purl.uniprot.org/uniprot/Q7TRT7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Keg1 ^@ http://purl.uniprot.org/uniprot/Q9DCY0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acyltransferase which transfers the acyl group to the N-terminus of glycine. Can conjugate a multitude of substrates to form a variety of N-acylglycines (By similarity).|||Belongs to the glycine N-acyltransferase family.|||Binds to microtubules.|||centrosome http://togogenome.org/gene/10090:Samhd1 ^@ http://purl.uniprot.org/uniprot/Q60710 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Phosphorylation at Thr-634 by mouse cytomegalovirus kinase M97 leads to a reduced level of dNTP hydrolase activity and the loss of viral restriction.|||Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers. Isoform 1: Phosphorylation at Thr-634 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses.|||Belongs to the SAMHD1 family.|||Binds 1 zinc ion per subunit.|||By interferon alpha, beta and gamma (IFN-alpha, IFN-beta and IFN-gamma).|||Chromosome|||Homodimer; in absence of GTP and dNTP (By similarity). Homotetramer; in GTP- and dNTP-bound form (PubMed:29379009). Interacts with MRE11; leading to stimulate the exonuclease activity of MRE11 (By similarity). Interacts with RBBP8/CtIP (By similarity). Interacts with RBBP8/CtIP. Interacts (via its C-terminus) with CD81.|||In mouse, the SAM domain is required for deoxynucleoside triphosphate (dNTPase) activity and ability to restrict infection by viruses. It acts by capping allosteric sites.|||Mice are viable and fertile but show increased cellular dNTP concentrations and impaired ability to restrict retroviral replication in lymphocytes, macrophages and dendritic cells (PubMed:23972988). Mice also display interferon (IFN)-beta-dependent transcriptional up-regulation of type I IFN-inducible genes in various cell types indicative of spontaneous IFN production (PubMed:23972988, PubMed:23872947). In addition, the replication of mouse cytomegalovirus is significantly enhanced in mutant mice (PubMed:31548683).|||Not phosphorylated by CDK1 at the C-terminus.|||Nucleus|||Phosphorylation at Thr-634 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions (PubMed:26667483) (By similarity). Phosphorylation at Thr-634 takes place in cycling cells: it reduces the stability of the homotetramer, impairing the dNTPase activity and subsequent ability to restrict infection by viruses (Probable). It also inhibits ability to suppress LINE-1 retrotransposon activity (PubMed:26667483). In contrast, phosphorylation at Thr-634 promotes DNA end resection at stalled replication forks in response to DNA damage (By similarity).|||Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (By similarity). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed:23972988, PubMed:23872947, PubMed:26667483, PubMed:31548683, PubMed:29379009). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:26667483). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (By similarity). Phosphorylation at Thr-634 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (By similarity). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (By similarity). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (By similarity). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (By similarity). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (PubMed:29669924). http://togogenome.org/gene/10090:Wdr44 ^@ http://purl.uniprot.org/uniprot/Q6NVE8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Downstream effector for Rab11 involved in the inhibition of the intracellular ciliogenesis pathway in concert with AKT1 kinase (By similarity). When the LPAR1 receptor signaling pathway is activated, phosphorylated WDR44 binds to Rab11, thus preventing the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex (By similarity). Together with Rab11, also participates in the regulation of vesicle recycling (By similarity).|||Endosome membrane|||Interacts with the GTP-bound form of RAB11 when membrane-associated. Does not bind to other Rab and Rho small G proteins.|||Phosphorylated by ATK1; the phosphorylation stabilizes its interaction with RAB11A and RAB11B.|||cytosol|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:H2ac25 ^@ http://purl.uniprot.org/uniprot/A2AB79|||http://purl.uniprot.org/uniprot/Q8BFU2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (By similarity). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Panx3 ^@ http://purl.uniprot.org/uniprot/Q6IMP0|||http://purl.uniprot.org/uniprot/Q8CEG0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the pannexin family.|||Cell membrane|||Expressed in skin, cartilage, heart, lung, liver, spleen, thymus and kidney. Not expressed in brain.|||Membrane|||N-glycosylation may play a role in cell surface targeting.|||Structural component of the gap junctions and the hemichannels.|||gap junction http://togogenome.org/gene/10090:Nphp3 ^@ http://purl.uniprot.org/uniprot/Q7TNH6 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Defects in Nphp3 may be the cause of polycystic kidney disease (pcy). Pcy is a recessive disorder causing chronic renal failure. The Pcy phenotype can be slowed by diet modification such as protein restriction, administration of soy-based proteins, administration of methylprednisolone or treatment with V2R antagonist. In contrast administration of bicarbonate/citrate has no effect.|||In gastrulation-stage embryos, it is confined to the node between 7.5 and 8.25 dpc In sections of 14.5 and 16.5 dpc. embryos, it is strongly expressed in neural tissue (brain and ganglions). Also weakly expressed included in kidney tubules, retina, respiratory epithelium, biliary tract and liver. In the adult kidney, it is weakly but specifically expressed in distal tubules located at the cortico-medullary border, which corresponds to the site of cyst formation in mice lacking Nphp3. Expressed in retina and liver.|||Interacts with NPHP1 and INVS/NPHP2. Interacts (when myristoylated) with UNC119 and UNC119B; interaction is required for localization to cilium (By similarity). Interacts with CEP164 (By similarity). Component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (By similarity).|||Mice show situs inversus, congenital heart defects, and embryonic lethality.|||Required for normal ciliary development and function. Inhibits disheveled-1-induced canonical Wnt-signaling activity and may also play a role in the control of non-canonical Wnt signaling that regulates planar cell polarity. Probably acts as a molecular switch between different Wnt signaling pathways. Required for proper convergent extension cell movements.|||cilium http://togogenome.org/gene/10090:C130074G19Rik ^@ http://purl.uniprot.org/uniprot/Q8BGN9 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Regulates drug efflux through modulation of ABCB1 localization and activity. http://togogenome.org/gene/10090:Izumo4 ^@ http://purl.uniprot.org/uniprot/D3Z690 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Izumo family.|||Izumo is the name of a Japanese shrine to marriage.|||Secreted http://togogenome.org/gene/10090:Tirap ^@ http://purl.uniprot.org/uniprot/H3BKL1|||http://purl.uniprot.org/uniprot/Q3UB38|||http://purl.uniprot.org/uniprot/Q542S6|||http://purl.uniprot.org/uniprot/Q99JY1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter involved in the TLR2 and TLR4 signaling pathways in the innate immune response.|||Adapter involved in the TLR2, TLR4 and RAGE signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response (By similarity). Positively regulates the production of TNF-alpha and interleukin-6 (By similarity).|||Cell membrane|||Cytoplasm|||Homodimer.|||Homodimer. Also forms heterodimers with MYD88. Interacts with BMX and TBK1 (By similarity). Interacts with TLR4 and IRAK2 via their respective TIR domains. Interacts with EIF2AK2. Does not interact with IRAK1-1, nor TLR9. May interact with PIK3AP1. Interacts with RAGE/AGER (By similarity).|||Membrane|||Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.|||Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation (By similarity). http://togogenome.org/gene/10090:Ctnnb1 ^@ http://purl.uniprot.org/uniprot/Q02248 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the beta-catenin family.|||Cell junction|||Cell membrane|||Cytoplasm|||Deacetylated at Lys-49 by SIRT1.|||Expressed in bell stage dental mesenchymal cells at 17.5 dpc (at protein level).|||Expressed in cerebellar granule neurons (at protein level) (PubMed:21623382). Expressed in the intestinal epithelium (at protein level) (PubMed:22510880).|||Key downstream component of the canonical Wnt signaling pathway (PubMed:15132997). In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes (By similarity). Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex (PubMed:16325582, PubMed:18093941). Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML (By similarity). Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle (PubMed:21325504). Involved in chondrocyte differentiation via interaction with SOX9: SOX9-binding competes with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (PubMed:15132997). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, via promoting the transcription of differentiation factors such as LEF1, BMP2 and BMP4 (PubMed:29148101). Activity is repressed in a MSX1-mediated manner at the bell stage of mesenchymal tooth germ formation which prevents premature differentiation of odontoblasts (PubMed:29148101).|||Nucleus|||O-glycosylation at Ser-23 decreases nuclear localization and transcriptional activity, and increases localization to the plasma membrane and interaction with E-cadherin CDH1.|||Phosphorylation at Ser-552 by AMPK promotes stabilization of the protein, enhancing TCF/LEF-mediated transcription (PubMed:20361929). Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase (By similarity). Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33 (By similarity). Phosphorylated by NEK2 (By similarity). EGF stimulates tyrosine phosphorylation (By similarity). Phosphorylated on Ser-33 and Ser-37 by HIPK2 and GSK3B, this phosphorylation triggers proteasomal degradation (PubMed:20307497). Phosphorylation on Ser-191 and Ser-246 by CDK5 (By similarity). Phosphorylation by CDK2 regulates insulin internalization (By similarity). Phosphorylation by PTK6 at Tyr-64, Tyr-142, Tyr-331 and/or Tyr-333 with the predominant site at Tyr-64 is not essential for inhibition of transcriptional activity (By similarity). Phosphorylation by SRC at Tyr-333 promotes interaction with isoform M2 of PKM (PKM2); promoting transcription activation (By similarity).|||S-nitrosylation at Cys-619 within adherens junctions promotes VEGF-induced, NO-dependent endothelial cell permeability by disrupting interaction with E-cadherin, thus mediating disassembly adherens junctions.|||Sympathetic ganglia-specific conditional knockout mice lead to a reduction in sympathetic ganglia size and in progenitor cell number, but does not alter sympathetic innervation of peripheral target organs.|||Synapse|||Two separate complex-associated pools are found in the cytoplasm. The majority is present as component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1 and beta-catenin/CTNNB1, and possibly alpha-catenin/CTNNA1; the complex is located to adherens junctions. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Binds NHERF1. Interacts with PTPRU (via the cytoplasmic juxtamembrane domain) and with EMD. Interacts with SESTD1 and TRPC4. Interacts with CAV1. Interacts with PTPRJ. Interacts with PKT7. Interacts with FAT1 (via the cytoplasmic domain). Interacts with CDK2, NDRG2 and NANOS1. Interacts with NEK2 and CDK5. Interacts with CARM1, CXADR, PCDH11Y and PTK6. Interacts with RAPGEF2. Interacts with SOX7; this interaction may lead to proteasomal degradation of active CTNNB1 and thus inhibition of Wnt/beta-catenin-stimulated transcription. Identified in a complex with HINT1 and MITF. Interacts with FHIT. Interacts with FERMT2. Identified in a complex with TCF4 and FERMT2. Another cytoplasmic pool is part of a large complex containing AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates, CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus, where it binds TCF/LEF-1 family members, BCL9, BCL9L and possibly also RUVBL1 and CHD8. Interacts with TAX1BP3 (via the PDZ domain); this interaction inhibits the transcriptional activity of CTNNB1. Interacts with AJAP1, BAIAP1 and CTNNA3. Interacts with TRPV4; the TRPV4 and CTNNB1 complex can interact with CDH1. Interacts with VCL. The CTNNB1 and TCF4 complex interacts with PML. Interacts with XIRP1. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding. Interacts directly with AXIN1; the interaction is regulated by CDK2 phosphorylation of AXIN1. Interacts with GLIS2. Interacts with SCRIB. Interacts with TNIK and TCF7L2. Interacts with SLC30A9. Interacts with RORA. May interact with P-cadherin/CDH3. Interacts with RNF220 (By similarity). Interacts with CTNND2 (By similarity). Interacts (via the C-terminal region) with CBY1 (By similarity). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (By similarity). Interacts with DLG5 (PubMed:25232112). Interacts with FAM53B; promoting translocation to the nucleus. Interacts with TMEM170B (By similarity). Interacts with AHI1 (By similarity). Interacts with GID8 (By similarity). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (By similarity). Forms a complex comprising APPL1, RUVBL2, APPL2, HDAC1 and HDAC2 (By similarity). Interacts with IRF2BPL; mediates the ubiquitination and degradation of CTNNB1 (By similarity). Interacts with AMFR (PubMed:31073040). Interacts with LMBR1L (PubMed:31073040). Interacts with SOX30; prevents interaction of CTNNB1 with TCF7L2/TCF4 and leads to inhibition of Wnt signaling (By similarity). Interacts with SOX9; inhibiting CTNNB1 activity by competing with the binding sites of TCF/LEF within CTNNB1, thereby inhibiting the Wnt signaling (PubMed:15132997). Interacts with SPN/CD43 cytoplasmic tail (By similarity). Interacts (when phosphorylated at Tyr-333) with isoform M2 of PKM (PKM2); promoting transcription activation (By similarity). Interacts with PKP2 (via HEAD domain) (By similarity). Interacts with CDH1 (By similarity). Interacts (when unphosphorylated) with FLYWCH1, perhaps preventing interaction of CTNNB1 with TCF4, and thereby regulating transcription activation; phosphorylation of CTNNB1 may inhibit the interaction (By similarity). Interacts (via the central armadillo domains) with probable transcriptional regulator ADNP (via N-terminal region); interaction is direct and stabilizes CTNNB1 by modulating its phosphorylation by glycogen synthase kinase-3 beta GSK3B (PubMed:32533114).|||Ubiquitinated by the SCF(BTRC) E3 ligase complex when phosphorylated by GSK3B, leading to its degradation (By similarity). Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X, leading to its subsequent proteasomal degradation (By similarity). Ubiquitinated and degraded following interaction with SOX9 (Probable).|||adherens junction|||centrosome|||cilium basal body|||cytoskeleton|||spindle pole http://togogenome.org/gene/10090:Snurf ^@ http://purl.uniprot.org/uniprot/Q9WU12 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SNURF family.|||Encoded on a bicistronic transcript that code for two proteins, SNRPN and SNURF. Only the primary 1.6-kb bicistronic SNURF-SNRPN transcript is detected.|||Expressed in brain and embryonic stem (ES) cells (at protein level). Expressed in the brain, ovary, testis, liver, heart, kidney and muscle.|||Nucleus http://togogenome.org/gene/10090:Rnf169 ^@ http://purl.uniprot.org/uniprot/E9Q7F2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNF169 family.|||Chromosome|||Interacts with DYRK1B.|||Phosphorylated by DYRK1A; phosphorylation increases RNF169 ability to block accumulation of TP53BP1 at the DSB sites.|||Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization. Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1. E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair.|||The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif also mediates interaction with ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs).|||nucleoplasm http://togogenome.org/gene/10090:Acsm5 ^@ http://purl.uniprot.org/uniprot/Q8BGA8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism.|||Mitochondrion matrix http://togogenome.org/gene/10090:Elac2 ^@ http://purl.uniprot.org/uniprot/Q3U0M8|||http://purl.uniprot.org/uniprot/Q80Y81 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase Z family.|||Homodimer. Interacts with PTCD1.|||Mitochondrion|||Nucleus|||Zinc phosphodiesterase, which displays mitochondrial tRNA 3'-processing endonuclease activity. Involved in tRNA maturation, by removing a 3'-trailer from precursor tRNA. Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Vta1 ^@ http://purl.uniprot.org/uniprot/Q9CR26 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VTA1 family.|||Cytoplasm|||Endosome membrane|||Interacts with VPS4B. Interacts with CHMP1B. Interacts with CHMP2A; the interaction probably involves the open conformation of (polymerized) CHMP2A. Interacts with CHMP3. Interacts with CHMP5; the interaction involves soluble CHMP5. Interacts with IST1 (By similarity).|||Involved in the endosomal multivesicular bodies (MVB) pathway. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. Thought to be a cofactor of VPS4A/B, which catalyzes disassembles membrane-associated ESCRT-III assemblies (By similarity). Involved in the sorting and down-regulation of EGFR.|||Widely expressed. Expressed in brain, liver, kidney, spleen, lung and heart (at protein level). http://togogenome.org/gene/10090:Septin8 ^@ http://purl.uniprot.org/uniprot/B1AQY9|||http://purl.uniprot.org/uniprot/B1AQZ0|||http://purl.uniprot.org/uniprot/B7ZC46|||http://purl.uniprot.org/uniprot/Q8CHH9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Filament-forming cytoskeletal GTPase (By similarity). May play a role in platelet secretion (By similarity). Seems to participate in the process of SNARE complex formation in synaptic vesicles (By similarity).|||Filament-forming cytoskeletal GTPase.|||May be due to a competing acceptor splice site.|||Presynapse|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation (By similarity). Interacts with SEPTIN5 (PubMed:12909369). Interacts with CDK14, SEPTIN4 and SEPTIN7 (By similarity). Interacts with VAMP2; the interaction inhibits interaction of VAMP2 with SYP (PubMed:19196426). Interacts with STX1A (By similarity).|||Septins polymerize into heterooligomeric protein complexes that form filaments.|||Synapse|||axon|||cytoskeleton|||synaptic vesicle membrane http://togogenome.org/gene/10090:Hspa4 ^@ http://purl.uniprot.org/uniprot/Q3U2G2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 70 family.|||Cytoplasm|||Interacts with TJP1/ZO-1. http://togogenome.org/gene/10090:Anapc7 ^@ http://purl.uniprot.org/uniprot/Q9WVM3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APC7 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity). APC7 is not required for the assembly of the APC/C complex, but has an enzyme-substrate adapter activity mediating the processive ubiquitination of specific substrates (By similarity). Involved in brain development through the specific ubiquitination and clearance of MKI67 from constitutive heterochromatin after neuronal progenitors exit mitosis (PubMed:34942119).|||Mice lacking Anapc7 show growth delay around weaning, although birth weight and adult size are normal. They show sensorimotor dysfunction in locomotive assays, as well as defects in the regulation of short- and long-term memory retrieval of the contextual fear response. Loss of the protein does not alter the anatomy of brain regions.|||Nucleus|||V-shaped homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Pmfbp1 ^@ http://purl.uniprot.org/uniprot/Q9WVQ0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the testis.|||Knockout male mice are infertile and have acephalic spermatozoa, while females are fertile and show normal follicle development.|||Required for normal spermatogenesis (PubMed:30032984, PubMed:30298696). It functions as a scaffold protein that attaches the sperm head-tail connecting piece to the nuclear envelope, thus maintaining sperm head and tail integrity (PubMed:30032984). May also be involved in the general organization of cellular cytoskeleton.|||flagellum http://togogenome.org/gene/10090:Eif3d ^@ http://purl.uniprot.org/uniprot/O70194 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit D family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.|||Cytoplasm|||The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of eif3d into the full eukaryotic translation initiation factor 3 (eIF-3) complex.|||mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs. http://togogenome.org/gene/10090:Ccl8 ^@ http://purl.uniprot.org/uniprot/Q149U7|||http://purl.uniprot.org/uniprot/Q9Z121 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic factor that attracts monocytes. This protein can bind heparin (By similarity).|||Monomer or homodimer; in equilibrium.|||Secreted http://togogenome.org/gene/10090:Ldb1 ^@ http://purl.uniprot.org/uniprot/P70662 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LDB family.|||Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors (PubMed:8918878, PubMed:9192866). May regulate the transcriptional activity of LIM-containing proteins by determining specific partner interactions (PubMed:8918878, PubMed:9315627, PubMed:9192866, PubMed:16815859, PubMed:18539116). Plays a role in the development of interneurons and motor neurons in cooperation with LHX3 and ISL1 (PubMed:12150931, PubMed:8876198, PubMed:18539116). Acts synergistically with LHX1/LIM1 in axis formation and activation of gene expression (PubMed:8918878). Acts with LMO2 in the regulation of red blood cell development, maintaining erythroid precursors in an immature state (PubMed:9391090).|||Due to intron retention. Lacks LIM-binding domain. Lacks ability to activate LIM domain-dependent transcription.|||Expressed in multiple adult tissues including heart, brain, liver, kidney, testis, lung and muscle, with expression highest in the pituitary gland and skin.|||Expression in the embryo overlaps that of LIM domain-containing proteins (PubMed:9192866). Expressed widely in the embryo with highest expression in several regions of the brain, and the central nervous system ganglia (PubMed:8918878, PubMed:9391090, PubMed:9192866). Also expressed in fetal liver, lung, kidney, thymus and olfactory epithelium (PubMed:9192866, PubMed:16815859, PubMed:9391090). Expressed in, but not restricted to, the basal compartment of interfollicular epidermis, the developing hair follicles during embryogenesis and, in adult hair, expressed in matrix cells and the outer root sheath (PubMed:9860983). Expressed in both embryonic and adult hemopoietic cells, including the erythroid lineage (PubMed:9391090).|||Interacts with ESR1 (By similarity). Forms homodimers and heterodimers (PubMed:9315627, PubMed:9468533). Interacts with and activates LHX1/LIM1 (PubMed:8918878, PubMed:9468533). Interacts with the LIM domains of ISL1 and LMO2 (PubMed:12150931, PubMed:12727888). Can assemble in a complex with LMO2 and TAL1/SCL but does not interact with TAL1/SCL directly (PubMed:9391090). Strongly interacts with the LIM2 domain of LMX1A and more weakly with the LIM1 domain (PubMed:9315627). Homodimerization is not required for, and does not effect, LMX1A-binding (PubMed:9315627). Component of a nuclear TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 (PubMed:16407974). Interacts with LHX6 and LHX9 (PubMed:10393337, PubMed:10330499). At neuronal promoters, forms a complex with LHX3 involved in the specification of interneurons, in motor neurons, it is displaced by ISL1 to form a ternary complex in which ISL1 contacts both LHX3 and LDB1 (PubMed:12150931, PubMed:18539116). Interacts with SLK; leading to negatively regulate SLK kinase activity (PubMed:19675209). Interacts with YWHAZ (By similarity). Interacts with PRDM1/BLIMP1 (By similarity). Interacts with LMO4 (PubMed:15343268, PubMed:9860983, PubMed:23353824). Interacts with RLIM/RNF12; the interaction inhibits the ubiquitination of LMO proteins (PubMed:11882901).|||Nucleus|||The dimerization domain is located in the N-terminus.|||Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Large2 ^@ http://purl.uniprot.org/uniprot/Q5XPT3 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 8 family.|||Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity and in a phosphorylated-O-mannosyl trisaccharide dependent manner (PubMed:15958417, PubMed:23125099, PubMed:23135544, PubMed:25138275). Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (PubMed:23125099, PubMed:23135544, PubMed:25138275). Supports the maturation of DAG1 more effectively than LARGE1 (By similarity). In addition, can modify both heparan sulfate (HS)- and chondroitin/dermatan sulfate (CS/DS)-proteoglycans (PGs), namely GPC4, with a glycosaminoglycan (GAG)-like polysaccharide composed of xylose and glucuronic acid to confer laminin binding (PubMed:27496765).|||Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn(2+).|||Golgi apparatus membrane|||Highly expressed in the testis and kidney, but weakly expressed in the heart and brain. Expressed during embryogenesis from 7 dpc.|||In the C-terminal section; belongs to the glycosyltransferase 49 family.|||In the N-terminal section; belongs to the glycosyltransferase 8 family.|||Interacts with B4GAT1.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Clec2i ^@ http://purl.uniprot.org/uniprot/Q9WVF9 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Detected in osteoblasts, growth plate chondrocytes and skeletal muscle overlying the bone (at protein level). Detected in spleen, B-cells, dendritic cells, thymus, and in IL2-activated natural killer cells.|||Inhibits osteoclast formation. Receptor for KLRB1F. Enhances T-cell activation. Plays a role in splenocyte activation, T-cell responses and IL-2 production.|||Up-regulated in CD4(+) T-cells upon stimulation with CD3-ligands. Up-regulated in cultured calvarial osteoblasts by 1,25-dihydroxyvitamin D3. Constitutively expressed in cultured bone marrow cells during osteoclast formation. http://togogenome.org/gene/10090:Pitpnb ^@ http://purl.uniprot.org/uniprot/P53811 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PtdIns transfer protein family. PI transfer class I subfamily.|||Catalyzes the transfer of phosphatidylinositol, phosphatidylcholine and sphingomyelin between membranes (By similarity). Required for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum; phosphatidylinositol and phosphatidylcholine transfer activity is essential for this function (By similarity).|||Constitutive phosphorylation of Ser-262 has no effect on phospholipid transfer activity but is required for Golgi targeting.|||Endoplasmic reticulum membrane|||Golgi apparatus|||Golgi apparatus membrane http://togogenome.org/gene/10090:Otx2 ^@ http://purl.uniprot.org/uniprot/Q8R0B5|||http://purl.uniprot.org/uniprot/Q8VD35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Nucleus http://togogenome.org/gene/10090:Mmp7 ^@ http://purl.uniprot.org/uniprot/Q3UN27 ^@ Cofactor|||Similarity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit. http://togogenome.org/gene/10090:Xrcc6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J187|||http://purl.uniprot.org/uniprot/P23475 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP3.|||Belongs to the ku70 family.|||Chromosome|||Expression increases during promyelocyte differentiation.|||Heterodimer composed of XRCC5/Ku80 and XRCC6/Ku70 (By similarity). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). Additional component of the NHEJ complex includes PAXX (By similarity). Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). The XRCC5-XRCC6 dimer also associates with NAA15, and this complex binds to the osteocalcin promoter and activates osteocalcin expression (By similarity). In addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 and DLX5 (By similarity). Interacts with ELF3 (By similarity). Interacts with ATP23 (By similarity). The XRCC5-XRRC6 dimer associates in a DNA-dependent manner with APEX1 (By similarity). Binds to CDK9 (By similarity). Identified in a complex with DEAF1 and XRCC5 (By similarity). Interacts with DEAF1 (via the SAND domain); the interaction is direct and may be inhibited by DNA-binding (By similarity). Interacts with CLU (PubMed:12551933). Interacts with NR4A3; the DNA-dependent protein kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with CYREN (via KBM motif) (PubMed:30017584). Interacts (via N-terminus) with HSF1 (via N-terminus); this interaction is direct and prevents XRCC5/XRCC6 heterodimeric binding and non-homologous end joining (NHEJ) repair activities induced by ionizing radiation (IR) (By similarity). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA (By similarity). Interacts with HMBOX1 (By similarity). Interacts with ATF7 (By similarity). Interacts with APLF (via KBM motif) (By similarity). Interacts with WRN (via KBM motif) (By similarity). The XRCC5-XRCC6 dimer associates with ALKBH2.|||Nucleus|||Phosphorylation by PRKDC may enhance helicase activity. Phosphorylation of Ser-49 does not affect DNA repair.|||Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (By similarity). Required for double-strand break repair and V(D)J recombination (By similarity). Also has a role in chromosome translocation (By similarity). Has a role in chromosome translocation (By similarity). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (By similarity). It works in the 3'-5' direction (By similarity). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (By similarity). Binding to DNA may be mediated by XRCC6 (By similarity). The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (By similarity). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (By similarity). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (By similarity). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (By similarity). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (By similarity). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (By similarity). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (By similarity).|||Viable. Reduced number of peripheral lymphocytes, however number of erythrocytes, platelets and neutrophils are normal. Translation levels in erythrocyte precursors are normal. http://togogenome.org/gene/10090:Adamts6 ^@ http://purl.uniprot.org/uniprot/D3Z1A5 ^@ Caution|||Cofactor|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular matrix http://togogenome.org/gene/10090:Dclk3 ^@ http://purl.uniprot.org/uniprot/Q8BWQ5 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Cytoplasm|||Highly expressed in brain and to a lower extent in liver and kidney.|||Nucleus http://togogenome.org/gene/10090:Vps50 ^@ http://purl.uniprot.org/uniprot/Q8CI71 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN).|||Belongs to the syndetin family.|||Component of the endosome-associated retrograde protein (EARP) complex, composed of VPS51, VPS52, VPS53 and VPS50/Syndetin (By similarity). The EARP complex interacts with EIPR1 (By similarity). Interacts with VPS51 and VPS53 in an EIPR1-independent manner (By similarity).|||Membrane|||Recycling endosome http://togogenome.org/gene/10090:Vmn2r90 ^@ http://purl.uniprot.org/uniprot/E9PXJ8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Th ^@ http://purl.uniprot.org/uniprot/P24529 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.|||Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of cathecolamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to L-Dopa (By similarity). In addition to tyrosine, is able to catalyze the hydroxylation of phenylalanine and tryptophan with lower specificity (By similarity). Positively regulates the regression of retinal hyaloid vessels during postnatal development(PubMed:30936473).|||Cytoplasm|||Expressed in the adrenal gland (PubMed:1674869). Expressed in the retina (PubMed:30936473). Expressed in the in the striatum (at protein level) (PubMed:17296554).|||Expressed in the retinal inner nuclear layer and outer nuclear layer at postnatal day 8 (P8) (PubMed:30936473). Expressed in retinal dopaminergic amacrine cells in the retina at P8 and P15 (PubMed:30936473).|||Homotetramer. Interacts (when phosphorylated at Ser-19) with YWHAG; one YWHAG dimer bounds to one TH tetramer this interaction may influence the phosphorylation and dephosphorylation of other sites.|||Homozygotes deficient mice are deficient in catecholamines, and usually die around embryonic day 11.5-15.5 due to cardiac failure (PubMed:7715703). Increased number of persisting retinal hyaloid vessels due to loss of hyaloid vessel regression at P8 (PubMed:30936473).|||Inhibited in feedback fashion by the catecholamine neurotransmitters, especially by dopamine in competition with tetrahydrobiopterin. Phosphorylation of several Ser/Thr residues in the N-terminus regulates the catalytic activity. Ser-31 and Ser-40 are readily phosphorylated to activate the catalytic activity. A Cysteine modification induced by N-ethylmaleimide (NEM), inhibits tyrosine 3-monooxygenase activity through the modification of the Cys-177.|||Nucleus|||Phosphorylated on Ser-19, Ser-31 and Ser-40 by several protein kinases with different site specificities. Phosphorylation at Ser-31 and Ser-40 leads to an increase of TH activity. Phosphorylation at Ser-40 activates the enzyme and also counteracts the feedback inhibition of TH by catecholamines (By similarity). Phosphorylation of Ser-19 and Ser-31 triggers the proteasomal degradation of TH through the ubiquitin-proteasome pathway (By similarity). Phosphorylation at Ser-31 facilitates transport of TH from the soma to the nerve terminals via the microtubule network (By similarity). Phosphorylation at Ser-19 induces the high-affinity binding to the 14-3-3 protein YWHAG; this interaction may influence the phosphorylation and dephosphorylation of other sites (By similarity). Ser-19 increases the phosphorylation at Ser-40 in a hierarchical manner, leading to increased activity (By similarity).|||axon|||perinuclear region|||synaptic vesicle http://togogenome.org/gene/10090:Coq8b ^@ http://purl.uniprot.org/uniprot/E9QLB8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. ADCK protein kinase family.|||Membrane http://togogenome.org/gene/10090:Tpd52l1 ^@ http://purl.uniprot.org/uniprot/O54818 ^@ Similarity|||Subunit ^@ Belongs to the TPD52 family.|||Forms a homodimer or heterodimer with other members of the family. http://togogenome.org/gene/10090:Dstyk ^@ http://purl.uniprot.org/uniprot/Q6XUX1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation. Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death. In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types.|||Apical cell membrane|||At 14.5 dpc detected in lung and skeletal muscle, and by 18.5 dpc detected in skin, whisker, gut and testis.|||Basolateral cell membrane|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cell junction|||Cell membrane|||Cytoplasm|||Expressed in brain, heart, skeletal muscle, kidney and lung. Expressed in maturing tubular epithelia, with the most prominent expression in the medulla and the papilla. Expressed in thin ascending limb of the loop of Henle and the distal convoluted tubule. Expressed in all layers of transitional ureteric epithelium and in the ureteric smooth-muscle cells (at protein level). Widely expressed. Highly expressed in many brain regions, including in cerebellum, olfactory, hippocampus and cerebral cortex. http://togogenome.org/gene/10090:Mepce ^@ http://purl.uniprot.org/uniprot/Q8K3A9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily.|||Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1). Interacts with METTL16. Interacts with RBM7; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core, yielding to P-TEFb complex activation.|||Nucleus|||S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA (7SK RNA), leading to stabilize it (By similarity). Also has a non-enzymatic function as part of the 7SK RNP complex: the 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:23154982). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (By similarity). In the 7SK RNP complex, MEPCE is required to stabilize 7SK RNA and facilitate the assembly of 7SK RNP complex (By similarity). MEPCE has a non-enzymatic function in the 7SK RNP complex; it has a non-enzymatic function; interaction with LARP7 within the 7SK RNP complex occluding its catalytic center (By similarity). http://togogenome.org/gene/10090:Ins2 ^@ http://purl.uniprot.org/uniprot/P01326|||http://purl.uniprot.org/uniprot/Q5EEX1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the insulin family.|||Heterodimer of a B chain and an A chain linked by two disulfide bonds.|||Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.|||Secreted http://togogenome.org/gene/10090:Pirt ^@ http://purl.uniprot.org/uniprot/Q8BFY0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ First expressed in DRG neurons around embryonic day 11.5, and expression is maintained throughout adulthood.|||Interacts with TRPV1.|||Membrane|||Mice show impaired responsiveness to noxious heat and capsaicin. Noxious heat- and capsaicin-sensitive currents in DRG neurons are significantly attenuated.|||Regulatory subunit of TRPV1, a molecular sensor of noxious heat and capsaicin. Positively regulates TRPV1 channel activity via phosphatidylinositol 4,5-bisphosphate (PIP2). Binds various phosphoinositide, including phosphatidylinositol 4,5-bisphosphate (PIP2), but not phosphatidylinositol (PI).|||Strongly expressed in most dorsal root ganglia (DRG) and trigeminal neurons. Expressed by most peptidergic (CGRP+) and non-peptidergic (IB4+) DRG neurons. Weakly expressed in other parts of the peripheral nervous system (PNS) including sympathetic and enteric neurons. Not expressed in the spinal cord. http://togogenome.org/gene/10090:Lgr5 ^@ http://purl.uniprot.org/uniprot/Q9Z1P4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the intestinal epithelium (at protein level) (PubMed:22510880). Expressed in the gonads, the adrenal gland, and in the brain. In the central nervous system expression is restricted to the olfactory bulb. In the adrenal gland detected only in the neural-crest derived chromaffin cells of the medulla, but not in the cells of the adrenal cortex. In the gonads, the expression is high in Graafian follicle, but absent from primary and secondary follicles. In the intestine, exclusively expressed in cycling crypt base columnar cells. Expressed in the lower bulge and secondary germ area of telogen hair follicles and in the lower outer root sheath of anagen hair follicle.|||First expressed at 8.5 dpc in a few cells of the ectoplacental cone and, at 9.5 dpc, in a greater number of cells in the labyrinthine region of the forming placenta. In the embryo per se, expression starts at 9.5 dpc. At 10.5 dpc, detected in the facial area in the tissue overlaying the mandibular cleft and in the optic cup. In the central nervous system, expressed in the neuroepithelium at the roof of the mesencephalon and in the spinal cord. At 11.5 dpc, in the central nervous system, expressed in the neuroepithelium at the border between mes- and metencephalon and that lining the fourth ventricle and the retina, as well as in the spinal cord. Outside the nervous system, at 11.5 dpc, expressed in the mesenchyme over-laying the mandibular cleft, in the distal limb buds, especially the hind limb buds, as well as in the perichordal mesenchyme in the rostral region of the embryo. At 12.5 dpc, in the central nervous system, highly expressed in the rhombencephalic isthmus. In the facial area, expressed in the mesenchyme surrounding the olfactory epithelium and the forming vibrissae. Expression in the hind and front limb buds increases and spreads to more proximal directions, but is restricted to the area were the digits develop. At 13.5 dpc, the expression in the brain becomes restricted to the border between mes- and diencephalon. Also detected in the pituitary. Strongly expressed in the mesenchyme adjacent to the mandibular cleft, as well as in the most lateral aspects of the tongue and the teeth anlagen. Weak expression in the body wall and mesenchyme surrounding internal organs. At 14.5 dpc, becomes hardly detectable in the nervous system. In the body, expressed in the perichondrium, but levels decrease with ongoing age (PubMed:9920770). In the limbs, at 14.5 dpc, expressed in the mesenchyme, but not in the overlying ectoderm of the limb bud. In developing lungs, at 14.5 dpc, expressed at low levels in both the epithelium and mesenchyme lineages (PubMed:29769720).|||Identified in a complex composed of RNF43, LGR5 and RSPO1 (By similarity). Also interacts with other R-spondin ligands, including RSPO2, RSPO3 and RSPO4 (By similarity).|||LGR5 is used as a marker of adult tissue stem cells in the intestine, stomach, hair follicle, and mammary epithelium.|||Mice exhibit malformation of the tongue and of lower jam causing newborns to swallow air leading to 100% neonatal lethality. Conditional knockout of both Lgr4 and Lgr5 in the gut results in Wnt signaling inhibition and results in the rapid demise of intestinal crypts (PubMed:21727895). Simultaneous knockdown of LGR4, LGR5 and LGR6 results in developmental phenotypes, such as cleft palate and ankyloglossia, but not in tetra-amelia with lung agenesis (PubMed:29769720).|||Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Dab1 ^@ http://purl.uniprot.org/uniprot/P97318 ^@ Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Adapter molecule functioning in neural development. May regulate SIAH1 activity.|||Associates with the SH2 domains of SRC, FYN and ABL. Interacts (phosphorylated on tyrosine residues) with CRK and CRKL (via respective SH2 domain) (PubMed:15062102). Interacts with SIAH1, LRP8 and VLDLR (PubMed:12646221, PubMed:12737822). Interacts with LRP1 (By similarity). Interacts with APLP1 (via NPXY motif) (PubMed:12826668). Interacts with DAB2IP (By similarity).|||Expressed mainly in brain.|||Phosphorylated on Tyr-198 and Tyr-220 upon reelin induction in embryonic neurons (PubMed:11279201). Also found phosphorylated on Tyr-232 upon reelin induction (PubMed:15062102). Also phosphorylated on Ser-524 independently of reelin signaling.|||The PID domain specifically binds to the Asn-Pro-Xaa-Tyr(P) motif found in many tyrosine-phosphorylated proteins. http://togogenome.org/gene/10090:Or14j1 ^@ http://purl.uniprot.org/uniprot/Q14AJ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rngtt ^@ http://purl.uniprot.org/uniprot/O55236|||http://purl.uniprot.org/uniprot/Q3UA94|||http://purl.uniprot.org/uniprot/Q9DCC1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Bifunctional mRNA-capping enzyme exhibiting RNA 5'-triphosphate monophosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part. Catalyzes the first two steps of cap formation: by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and by transferring the GMP moiety of GTP to the 5'-diphosphate terminus of RNA via a covalent enzyme-GMP reaction intermediate.|||In the C-terminal section; belongs to the eukaryotic GTase family.|||In the N-terminal section; belongs to the non-receptor class of the protein-tyrosine phosphatase family.|||Interacts with SUPT5H and RNMT (By similarity). Interacts with POLR2A (via C-terminus); this enhances guanylyltransferase activity. Binds (via GTase domain) to the elongating phosphorylated form of RNA polymerase II; can form direct interactions with the phosphorylated POLR2A C-terminal domain and indirect interactions via bound RNA.|||Nucleus|||RNA triphosphatase activity is inhibited by vanadate, iodoacetate and magnesium. http://togogenome.org/gene/10090:Orai2 ^@ http://purl.uniprot.org/uniprot/A5CVE1|||http://purl.uniprot.org/uniprot/Q14BR6|||http://purl.uniprot.org/uniprot/Q8BH10 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Orai family.|||Ca(2+) release-activated Ca(2+)-like (CRAC-like) channel subunit which mediates Ca(2+) influx and increase in Ca(2+)-selective current by synergy with the Ca(2+) sensor, STIM1.|||Interacts with CRACR2A/EFCAB4B.|||Membrane http://togogenome.org/gene/10090:Qrfprl ^@ http://purl.uniprot.org/uniprot/G3UWA8|||http://purl.uniprot.org/uniprot/Q8BHH0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane http://togogenome.org/gene/10090:Krtap8-1 ^@ http://purl.uniprot.org/uniprot/O08633 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 8 family.|||Expression restricted exclusively to the cortical cells of hair follicles.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:4930451I11Rik ^@ http://purl.uniprot.org/uniprot/E9Q9R3 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Deficient mice have no overt developmental abnormalities. Furthermore, no deleterious effects on testicular histology and sperm morphology are observed. However male mice are severely subfertile, their spermatozoa show impaired ability to fuse with the oocytes.|||Plays a role in sperm-oocyte fusion process during fertilization.|||Secreted|||Testis-specific. http://togogenome.org/gene/10090:Akr1d1 ^@ http://purl.uniprot.org/uniprot/Q8VCX1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the aldo/keto reductase family.|||Catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure to yield an A/B cis-ring junction. This cis-configuration is crucial for bile acid biosynthesis and plays important roles in steroid metabolism. Capable of reducing a broad range of delta-(4)-3-ketosteroids from C18 (such as, 17beta-hydroxyestr-4-en-3-one) to C27 (such as, 7alpha-hydroxycholest-4-en-3-one).|||Cytoplasm|||Subject to inhibition by high substrate concentrations. Inhibited by testosterone concentrations above 10 uM. Inhibited by the primary and secondary bile acids chenodeoxycholic acid and ursodeoxycholic acid. http://togogenome.org/gene/10090:Trpm2 ^@ http://purl.uniprot.org/uniprot/Q91YD4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM2 sub-subfamily.|||Cell membrane|||Cell projection|||Cytoplasmic vesicle|||Detected in the preoptic area of the hypothalamus, a brain area involved in body temperature control (PubMed:27562954). Detected in beta-cells in pancreas islets (at protein level) (PubMed:16601673, PubMed:20921208). Detected in brain cortex, striatum, hippocampus CA1, CA2 and CA3 layers, and in the Purkinje cell layer in cerebellum (PubMed:15708008). Widely expressed, with highest levels in lung, spleen, eye and brain (PubMed:11804595). Detected in dendritic cells and in polymorphonuclear neutrophils (PubMed:21753080).|||Homotetramer.|||Lysosome|||Mutant mice display no obvious phenotype, but display increased blood glucose levels when fed ad libitum (PubMed:20921208). After oral or intraperitoneal glucose administration, they display increased blood glucose and lower plasma insulin levels; basal fasting glucose and insulin levels are not altered (PubMed:20921208). Ca(2+) influx into beta-cells is unchanged under basal conditions or upon stimulation with glucose up to 8.3 mM; Ca(2+) influx is decreased upon stimulation with high glucose levels (16.7 mM) (PubMed:20921208). Likewise, insulin secretion is decreased only upon stimulation with 11.2 or 16.7 mM glucose, but not in response to more moderate glucose levels (PubMed:20921208). Mutant mice have a reduced number of neurons that are activated by warm temperature (34 to 43 degrees Celsius) in their dorsal root ganglia and superior cervical ganglia (PubMed:27533035). Mutant mice show altered behavorial responses to environmental temperature; contrary to wild-type they show no preference for a cooler environment when exposed to 38 degrees Celsius (PubMed:27533035). Besides, they spend less time than wild-type in a cooler environment (23 degrees Celsius) (PubMed:27533035). Mutant mice develop higher fever in response to prostaglandin E2 injection into the preoptic area of the hypothalamus, a brain area involved in body temperature control (PubMed:27562954). Mutant mice display a defective innate immune response and are highly susceptible to infection by L.monocytogenes (PubMed:21709234). They are unable to contain the bacterial infection; contrary to wild-type, they die within a few days after infection (PubMed:21709234). The defective immune response is due to impaired secretion of Il12b and IFNG; mice are rescued by treatment with recombinant IFNG (PubMed:21709234).|||Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11804595, PubMed:19454650, PubMed:21753080, PubMed:22493272). Functions as ligand-gated ion channel. Binding of ADP-ribose to the cytoplasmic Nudix domain causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening. Extracellular calcium passes through the channel and increases channel activity (By similarity). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:21753080). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (PubMed:21753080). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (By similarity). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:27533035, PubMed:27562954). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:19454650, PubMed:21753080, PubMed:22493272). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate. Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (By similarity). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272, PubMed:25817999). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis (PubMed:27533035, PubMed:27562954). Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (PubMed:20921208, PubMed:25817999). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection (PubMed:21709234). Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro) (PubMed:22493272). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (PubMed:21753080). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its function in increasing cytoplasmic Ca(2+) and Zn(2+) levels (By similarity). Confers susceptibility to cell death following oxidative stress (PubMed:25562606).|||Perikaryon|||The cytosolic nudix box binds ADP-ribose and is required for channel activation by ADP-ribose. http://togogenome.org/gene/10090:Ube2a ^@ http://purl.uniprot.org/uniprot/Q3UCS1|||http://purl.uniprot.org/uniprot/Q9Z255 ^@ Function|||PTM|||Similarity|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA.|||Belongs to the ubiquitin-conjugating enzyme family.|||Interacts with RAD18 and WAC (By similarity). Interacts with RFPL4A and CCNB1 (PubMed:12525704).|||Phosphorylation at Ser-120 by CDK9 increases activity towards histone H2B. http://togogenome.org/gene/10090:Nfs1 ^@ http://purl.uniprot.org/uniprot/Q9Z1J3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Active only in complex with LYRM4.|||Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.|||Cysteine persulfide intermediate is reduced by thiol-containing molecules like glutathione and L-cysteine (PubMed:25597503). Persulfide reduction is a rate-limiting step of cysteine desulfurase catalytic cycle (PubMed:25597503).|||Homodimer (By similarity). Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer (By similarity). Component of cyteine desulfurase complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes to the activation of cysteine desulfurase activity and NFS1 stabilization. Interacts (homodimer form) with ISCU (D-state); each monomer interacts with the C-terminal regions of each NFS1 monomer. Interacts with HSPA9. Interacts (via homodimer form) with FDX2. Interacts (via homodimer form) with FXN. Interacts with LYRM4 (By similarity). Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (PubMed:21298097, PubMed:25597503).|||Mitochondrial cysteine desulfurase, of the core iron-sulfur cluster (ISC) assembly complex, that catalyzes the desulfuration of L-cysteine to L-alanine, as component of the cysteine desulfurase complex, leading to the formation of a cysteine persulfide intermediate at the active site cysteine residue and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (PubMed:25597503). The persulfide is then transferred on the flexible Cys loop from the catalytic site of NFS1 to the surface of NFS1 (By similarity). After the NFS1-linked persulfide sulfur is transferred to one of the conserved Cys residues of the scaffold, a reaction assisted by FXN (PubMed:25597503). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity).|||Mitochondrion|||N-gluconoylated.|||Ubiquitous. http://togogenome.org/gene/10090:Or1e1c ^@ http://purl.uniprot.org/uniprot/E9Q4M1|||http://purl.uniprot.org/uniprot/Q8VGI2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnq2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFQ2|||http://purl.uniprot.org/uniprot/B7ZBV4|||http://purl.uniprot.org/uniprot/B7ZBV5|||http://purl.uniprot.org/uniprot/B7ZBV6|||http://purl.uniprot.org/uniprot/B7ZBV7|||http://purl.uniprot.org/uniprot/B7ZBV8|||http://purl.uniprot.org/uniprot/B7ZBV9|||http://purl.uniprot.org/uniprot/B7ZBW1|||http://purl.uniprot.org/uniprot/B7ZBW2|||http://purl.uniprot.org/uniprot/Q3UY10|||http://purl.uniprot.org/uniprot/Q9Z351 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. Therefore, it is important in the regulation of neuronal excitability (PubMed:12223552). KCNQ2-KCNQ3 channel is selectively permeable to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+). Associates with Na(+)-coupled myo-inositol symporter SLC5A3 forming a coregulatory complex that alters ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (By similarity).|||Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.2/KCNQ2 sub-subfamily.|||Cell membrane|||Detected at day 11, 15 and 17 of the embryonic development. Expression increases by a factor of 2.5 at 1 week after birth. Then the expression level remains stable until the adult stage. The mRNAs for shorter forms (isoforms 9, 10 and 11) are specifically expressed in an embryo on the 11th day after gestation.|||Exclusively expressed in the brain. Expressed in every neuron-containing regions of the central nervous system examined, such as the cerebellum, cerebral cortex, occipital pole, substantia nigra, amygdala, caudate nucleus, hippocampus and thalamus. Also detected in the cochlea.|||Heterotetramer with KCNQ3; form the heterotetrameric M potassium channel (By similarity). Interacts with calmodulin; the interaction is calcium-independent, constitutive and participates in the proper assembly of a functional heterotetrameric M channel (PubMed:12223552). May associate with KCNE2 (By similarity). Interacts with IQCJ-SCHIP1 (PubMed:27979964). Interacts (via the pore module) with SLC5A3; forms a coregulatory complex that alters ion selectivity, voltage dependence and gating kinetics of the channel.|||KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to protein degradation. Degradation induced by NEDD4L is inhibited by USP36.|||KCNQ2/KCNQ3 heteromeric current can be increased by intracellular cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the N-terminal region.|||May be due to an intron retention.|||Membrane|||Mice lacking Kcnq2 present no overt phenotype, but die a few hours after birth of pulmonary atelectasis which is not due to the status of epileptic seizures.|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Ndufaf6 ^@ http://purl.uniprot.org/uniprot/A2AIL4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NDUFAF6 family.|||Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages. May play a role in the biogenesis of complex I subunit MT-ND1.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Fam174c ^@ http://purl.uniprot.org/uniprot/Q9DAZ5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM174 family.|||Membrane http://togogenome.org/gene/10090:Tanc2 ^@ http://purl.uniprot.org/uniprot/A2A690 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TANC family.|||Interacts with KIF1A; the interaction decreases in presence of calcium.|||Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines.|||dendritic spine http://togogenome.org/gene/10090:Por ^@ http://purl.uniprot.org/uniprot/P37040 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NADPH--cytochrome P450 reductase family.|||Binds 1 FAD per monomer.|||Binds 1 FMN per monomer.|||Endoplasmic reticulum membrane|||In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||In the N-terminal section; belongs to the flavodoxin family.|||This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5. http://togogenome.org/gene/10090:Msh4 ^@ http://purl.uniprot.org/uniprot/A0A087WQN0|||http://purl.uniprot.org/uniprot/A6H6D5|||http://purl.uniprot.org/uniprot/Q7TNA7|||http://purl.uniprot.org/uniprot/Q99MT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA mismatch repair MutS family.|||Chromosome|||Heterooligomer of MSH4 and MSH5.|||Involved in meiotic recombination. Required for reciprocal recombination and proper segregation of homologous chromosomes at meiosis.|||Predominantly expressed in testis. http://togogenome.org/gene/10090:Nr2f2 ^@ http://purl.uniprot.org/uniprot/P43135|||http://purl.uniprot.org/uniprot/Q3UST6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR2 subfamily.|||Interacts with SQSTM1. Binds DNA as a dimer; homodimer or heterodimer with NR2F6. Interacts with NCOA1, NCOA2, NCOA3 and PPARGC1A (By similarity). Interacts with ZFPM2.|||Ligand-activated transcription factor. Activated by high concentrations of 9-cis-retinoic acid and all-trans-retinoic acid, but not by dexamethasone, cortisol or progesterone (in vitro). Regulation of the apolipoprotein A-I gene transcription. Binds to DNA site A. May be required to establish ovary identity during early gonad development.|||Nucleus http://togogenome.org/gene/10090:Hsd3b7 ^@ http://purl.uniprot.org/uniprot/Q9EQC1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Predominantly expressed in liver.|||The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. Does not metabolize several different C(19/21) steroids as substrates. Involved in bile acid synthesis (PubMed:11067870). Plays a key role in cell positioning and movement in lymphoid tissues by mediating degradation of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC): 7-alpha,25-OHC acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells (PubMed:22999953). http://togogenome.org/gene/10090:Hook3 ^@ http://purl.uniprot.org/uniprot/Q8BUK6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with Salmonella typhimurium spiC.|||(Microbial infection) Serves as a target for the spiC protein from Salmonella typhimurium, which inactivates it, leading to a strong alteration in cellular trafficking.|||Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor. Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). May regulate clearance of endocytosed receptors such as MSR1. Participates in defining the architecture and localization of the Golgi complex. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.|||Belongs to the hook family.|||Expressed in brain, cerebellum, heart, intestine, kidney, liver, lung, skeletal muscle, spleen and stomach (at protein level).|||Golgi apparatus|||Self-associates (By similarity). Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3 (By similarity). May interact directly with AKTIP/FTS, HOOK1 and HOOK2 (By similarity). Associates with several subunits of the homotypic vesicular sorting complex (the HOPS complex) including VPS16 and VPS41; these interactions may be indirect (By similarity). Interacts with IIGP1 (PubMed:15075236). Interacts with MSR1, and this association is stimulated by ligand binding to MSR1 (PubMed:17237231). Interacts with microtubules. Part of a tripartite complex with dynein and dynactin, acts an adapter linking the dynein motor complex and dynactin (By similarity). Interacts with dynein intermediate chain and dynactin (DCTN1) (By similarity). Interacts with CCDC181 (PubMed:28283191). Interacts with LRGUK (PubMed:28003339).|||cytoskeleton http://togogenome.org/gene/10090:Cyp4f14 ^@ http://purl.uniprot.org/uniprot/Q9EP75 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. Catalyzes the omega-hydroxylation of LTB4 (By similarity).|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Ms4a4a ^@ http://purl.uniprot.org/uniprot/A0A087WRT7 ^@ Similarity ^@ Belongs to the MS4A family. http://togogenome.org/gene/10090:Cd320 ^@ http://purl.uniprot.org/uniprot/Q9Z1P5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Interacts (via LDL-receptor class A domains) with TCN2.|||Receptor for transcobalamin saturated with cobalamin (TCbl). Plays an important role in cobalamin uptake. Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells. Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation. Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10. http://togogenome.org/gene/10090:Mthfr ^@ http://purl.uniprot.org/uniprot/A2A7F7|||http://purl.uniprot.org/uniprot/Q3UDB2|||http://purl.uniprot.org/uniprot/Q9WU20 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subunit ^@ Allosterically regulated by S-adenosylmethionine (SAM).|||Belongs to the methylenetetrahydrofolate reductase family.|||Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Represents a key regulatory connection between the folate and methionine cycles.|||Contains a serine-rich phosphorylation region at the N-terminal and an eukaryote-only S-adenosylmethionine (SAM)-binding domain at the C-terminal. Through asymmetric homodimerization, the two regions are positioned next to each other and N-terminal phosphorylation increases sensitivity to SAM binding and inhibition.|||Homodimer.|||Phosphorylation of an N-terminal serine-rich phosphorylation region increases sensitivity to S-adenosylmethionine and inhibition. http://togogenome.org/gene/10090:Klk1b11 ^@ http://purl.uniprot.org/uniprot/P15946 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Usp17ld ^@ http://purl.uniprot.org/uniprot/G5E8G2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C19 family. USP17 subfamily.|||Detected in T-cell, myeloid, and embryonic stem cell lines.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes that may include cell proliferation, progression through the cell cycle, apoptosis, cell migration, and the cellular response to viral infection.|||Endoplasmic reticulum|||Nucleus http://togogenome.org/gene/10090:Gtpbp6 ^@ http://purl.uniprot.org/uniprot/Q3U6U5 ^@ Similarity ^@ Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. HflX GTPase family. http://togogenome.org/gene/10090:Pja1 ^@ http://purl.uniprot.org/uniprot/O55176 ^@ Domain|||Function|||Induction|||PTM|||Subunit|||Tissue Specificity ^@ Binds ubiquitin-conjugating enzymes (E2s). Binds, in vitro and in vivo, the MAGE conserved domain of MAGED1. Binds weakly Necdin, in vitro. Interacts with UBE2D2.|||By fear memory. Differential induction of isoforms.|||Expressed in brain, liver, kidney. Highest levels in brain where it is found in many regions including cortical and subcortical areas and in neurons of the amygdala. Weak expression also found in testis. Also expressed in developing embryo.|||Has E2-dependent E3 ubiquitin-protein ligase activity. Ubiquitinates MAGED1 antigen leading to its subsequent degradation by proteasome. May be involved in protein sorting.|||Substrate for E2-dependent ubiquitination.|||The RING-type zinc finger domain interacts with an ubiquitin-conjugating enzyme (E2) and facilitates ubiquitination. http://togogenome.org/gene/10090:Thrsp ^@ http://purl.uniprot.org/uniprot/Q543J4|||http://purl.uniprot.org/uniprot/Q62264|||http://purl.uniprot.org/uniprot/Q8BPB6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPOT14 family.|||Cytoplasm|||Decreased lipid synthesis in the lactating mammary gland. Milk has reduced triglyceride content, causing reduced weight gain in nursing pups. Adults exhibit reduced body fat content. No effect on lipid synthesis in liver. No effect on the expression of thyroid hormone-induced lipogenic genes.|||Homodimer. Heterodimer with MID1IP1. Interacts with THRB and PLAGL1 (By similarity).|||Mainly expressed in tissues that synthesize triglycerides.|||Nucleus|||Plays a role in the regulation of lipogenesis, especially in lactating mammary gland. Important for the biosynthesis of triglycerides with medium-length fatty acid chains. May modulate lipogenesis by interacting with MID1IP1 and preventing its interaction with ACACA. May function as transcriptional coactivator. May modulate the transcription factor activity of THRB (By similarity). http://togogenome.org/gene/10090:Fam205a3 ^@ http://purl.uniprot.org/uniprot/C0HKD1|||http://purl.uniprot.org/uniprot/C0HKD2|||http://purl.uniprot.org/uniprot/C0HKD3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Brwd1 ^@ http://purl.uniprot.org/uniprot/Q921C3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Broadly expressed during development. Expression begins to increase at 7.5 dpc, peaks at 10.5-11.5 dpc, and decreases from 14.5 dpc. Weakly expressed at late embryonic stages.|||Cytoplasm|||Interacts with SMARCA4.|||May be a transcriptional activator. May be involved in chromatin remodeling. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Kcna1 ^@ http://purl.uniprot.org/uniprot/P16388 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||RNA Editing|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A spontaneous mutation leading to a frameshift and truncation of Kcna2 causes megencephaly with a 25% increase of brain weight relative to wild-type. Especially the hippocampus shows increased proliferation of neurons and astrocytes, leading to increased brain volume (PubMed:17315199). Mutant mice appear normal at birth. After 3-4 weeks, they display low body weight, a subtle shakiness in their gait, a preference for a strange sitting position that is maintained for periods ranging from 30 seconds to several minutes, excessive lacrimation and acoustic startle hypersensitivity (PubMed:8995755, PubMed:21966978). The increase in the acoustic startle response is down-regulated by treatment with the anti-epileptic drug valproate (PubMed:21966978). Mutant mice display an abnormal electro-encephalogram with single spikes and waves, when anesthesized (PubMed:21966978). The electric activity of mossy cells from the dentate hilus region is altered and shows increased firing of action potentials, probably due to the absence of functional Kcna1 channels (PubMed:14686897). Heterozygotes show mechanical allodynia, but no increased sensitivity to heat (PubMed:23473320). Homozygotes show no alteration of the islet of Langerhans structure, of the basal levels of insulin secretion and blood glucose levels (PubMed:21483673). Compared to wild-type, they display moderately increased insulin secretion in response to a glucose stimulus (PubMed:21483673). Besides, the frequency of beta cell action potentials is increased (PubMed:21483673).|||Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.1/KCNA1 sub-subfamily.|||Cell junction|||Cell membrane|||Cytoplasmic vesicle|||Detected in brain (PubMed:2451788, PubMed:9581771, PubMed:21483673, PubMed:22158511). Expressed in cerebellar cortex basket cell terminals, the area surround the Purkinje cell soma, and the pinceaux expansions encircling the axon initial segment (at protein level) (PubMed:26269648). Detected in the juxtaparanodal regions of the nodes of Ranvier in myelinated axons (PubMed:8361541, PubMed:8046438). Detected in the paranodal region in sciatic nerve (PubMed:9736643). Detected on cell bodies in cerebellum, dorsal and ventral cochlear nucleus, pontine reticular nucleus, mesencephalic trigeminal nucleus, motor trigeminal nucleus and the pricipal sensory trigeminal nucleus (PubMed:8046438). Detected in terminal fields of basket cells in the cerebellum corpus medullare (PubMed:8361541, PubMed:8046438, PubMed:9581771). Detected in hippocampus CA3 pyramidal neurons and in the hilus and stratum moleculare of the dentate gyrus (PubMed:8046438, PubMed:9581771, PubMed:14686897). Detected in the central nucleus and the external nucleus of the inferior colliculus (PubMed:8046438, PubMed:21966978). Detected in fiber tracts in the optic tract, external medullary lamina, stria terminalis, medulla, ventral pallidum and substantia nigra (PubMed:8046438). Detected in neurons from dorsal root ganglion (PubMed:23473320). Detected in neurons in the medial nucleus of the trapezoid body (PubMed:12611922). Detected in midbrain dopamine neuron axon terminals (PubMed:21233214). Detected in brain cortex (PubMed:8046438, PubMed:14686897). Detected in brainstem (PubMed:8361541). Detected in juxtaparanodal regions of the nodes of Ranvier in the vagus nerve, but only at very low levels in the heart (PubMed:20392939, PubMed:22641786). Detected in the islet of Langerhans (PubMed:21483673). Detected at the luminal membrane in distal convoluted tubules in the kidney (at protein level) (PubMed:19307729). Detected in hippocampus, thalamus, neocortex and ventral brain cortex, including the piriform and entorhinal cortex and the amygdala (PubMed:14686897). Detected in midbrain dopamine neurons (PubMed:21233214). Detected in heart atrium, ventricle, sinoatrial node and atrioventricular node (PubMed:20392939). Detected in the islet of Langerhans (PubMed:21483673).|||Down-regulated by high dietary Mg(2+) levels.|||Endoplasmic reticulum|||Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8361541). Channel activity is regulated by interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:15361858). Identified in a complex with KCNA2 and KCNAB2. Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with LGI1 within a complex containing LGI1, KCNA4 and KCNAB1 (By similarity). Interacts (via N-terminus) with STX1A; this promotes channel inactivation (By similarity). Interacts (via N-terminus) with the heterodimer formed by GNB1 and GNG2; this promotes channel inactivation (By similarity). Can interact simultaneously with STX1A and the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG; this inhibits channel activity (By similarity). Interacts with ANK3; this inhibits channel activity (PubMed:23903368). Interacts with ADAM11 (PubMed:26269648).|||Inhibited by 4-aminopyridine (4-AP), tetraethylammonium (TEA) and dendrotoxin (DTX), but not by charybdotoxin (CTX).|||Membrane|||Mice are born at the expected Mendelian rate. After three weeks, mice begin to display episodic eye blinking, twitching of whiskers, forlimb padding, arrested motion and a hyperstartle response. About 50% of the homozygotes die between the third and the fifth week after birth. Surviving mice continue to display spontaneous seizures occurring once or twice every hour throughout adult life (PubMed:9581771). The fecundity of homozygotes is extremely low (PubMed:9581771). Mutant mice display interictal cardiac abnormalities, including a fivefold increase in atrioventricular conduction blocks, brachycardia and premature ventricular contractions; this may lead to sudden unexplained death in epilepsy (PubMed:20392939). Mutant mice have slightly elevated heart rates; they all have a reduced livespan and are subject to sudden death after presumed seizure activity and sinus bradycardia (PubMed:25377007). About 70% of the mutant mice have an enlarged hippocampus and ventral brain cortex (PubMed:17250763). Mutant mice show a temperature-sensitive alteration in neuromuscular transmission, causing nerve hyperexcitability when exposed to cold and delayed repetitive discharge after a single nerve stimulation (PubMed:9736643). After 2 minutes of swimming in cold water, mutant mice have impaired motor control; they fall over when placed on dry ground and exhibit severe neuromyotonia with violent tremors that decrease with time, leading to full recovery after twenty minutes (PubMed:9736643). Mutant mice have an increased frequency of spontaneous postsynaptic currents in Purkinje cells, impaired ability to maintain their balance on a thin stationary rod, but perform as well as wild-type on a rotarod (PubMed:10191303). Mutant mice have a normal hearing threshold, but altered brainstem responses to auditory stimuli and reduced sensitivity to small changes in sound location (PubMed:22396426). Mutant mice display no alteration of the islet of Langerhans, but have reduced blood glucose levels and increased insulin secretion in response to a glucose stimulus (PubMed:21483673).|||N-glycosylated.|||Palmitoylated on Cys-243; which may be required for membrane targeting.|||Partially edited. RNA editing varies from 35% in the frontal cortex to 75% in the spinal chord.|||Perikaryon|||Phosphorylated on tyrosine residues. Phosphorylation increases in response to NRG1; this inhibits channel activity (PubMed:22158511). Phosphorylation at Ser-446 regulates channel activity by down-regulating expression at the cell membrane (By similarity).|||Presynapse|||Presynaptic cell membrane|||Synapse|||The cytoplasmic N-terminus is important for tetramerization and for interaction with the beta subunits that promote rapid channel closure.|||The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney. Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:9736643, PubMed:9581771, PubMed:10191303, PubMed:12611922, PubMed:21966978, PubMed:22158511, PubMed:23473320). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:15361858). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:15361858). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:7517498, PubMed:15361858). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability (PubMed:23466697). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (PubMed:20392939, PubMed:22641786, PubMed:25377007). Required for normal neuromuscular responses (PubMed:9736643). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (PubMed:23473320). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (PubMed:21966978, PubMed:22396426). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21233214). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (PubMed:8995755, PubMed:17250763, PubMed:17315199, PubMed:22411008). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (By similarity).|||axon|||dendrite http://togogenome.org/gene/10090:Magt1 ^@ http://purl.uniprot.org/uniprot/A2ADH1|||http://purl.uniprot.org/uniprot/Q9CQY5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with TUSC3. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Has also oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition.|||Accessory component of the STT3B-containing form of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. OST can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes. The association of TUSC3 or MAGT1 with the STT3B-containing complex seems to be mutually exclusvice.|||Belongs to the OST3/OST6 family.|||Cell membrane|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Expressed at high levels in kidney, colon, heart and liver. Expressed at lower levels in intestine, spleen, brain and lung.|||Induced by low magnesium levels.|||May be involved in Mg(2+) transport in epithelial cells.|||Membrane http://togogenome.org/gene/10090:Or5k3 ^@ http://purl.uniprot.org/uniprot/Q8VGQ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gnb4 ^@ http://purl.uniprot.org/uniprot/P29387 ^@ Function|||Similarity|||Subunit ^@ Belongs to the WD repeat G protein beta family.|||G proteins are composed of 3 units, alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Nudt5 ^@ http://purl.uniprot.org/uniprot/Q9JKX6 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family.|||Binds 3 Mg(2+) ions per subunit.|||Enzyme that can either act as an ADP-sugar pyrophosphatase in absence of diphosphate or catalyze the synthesis of ATP in presence of diphosphate (By similarity). In absence of diphosphate, hydrolyzes with similar activities various modified nucleoside diphosphates such as ADP-ribose, ADP-mannose, ADP-glucose, 8-oxo-GDP and 8-oxo-dGDP (PubMed:10722730). Can also hydrolyze other nucleotide sugars with low activity (PubMed:10722730). In presence of diphosphate, mediates the synthesis of ATP in the nucleus by catalyzing the conversion of ADP-ribose to ATP and ribose 5-phosphate (By similarity). Nuclear ATP synthesis takes place when dephosphorylated at Thr-44 (By similarity). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (By similarity). Does not play a role in U8 snoRNA decapping activity (PubMed:21070968). Binds U8 snoRNA (PubMed:21070968).|||Homodimer. Interacts with PARG.|||Nucleus|||Phosphorylation at Thr-44 is required for homodimer stability; dephosphorylation results in destabilization of the homodimer. Dephosphorylation at Thr-44 promotes the ATP-synthesis activity.|||Widely expressed. Most abundant in liver. http://togogenome.org/gene/10090:Unc13b ^@ http://purl.uniprot.org/uniprot/A0A140LHX5|||http://purl.uniprot.org/uniprot/E9Q263|||http://purl.uniprot.org/uniprot/Q9Z1N9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the unc-13 family.|||Cytoplasm|||Golgi apparatus|||Interacts with RIMS1.|||Membrane|||Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-depending refilling of readily releasable vesicle pool (RRP) (By similarity). Essential for synaptic vesicle maturation in a subset of excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. In collaboration with UNC13A, facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896).|||Synapse|||The C2 domains are not involved in calcium-dependent phospholipid binding. http://togogenome.org/gene/10090:Tff3 ^@ http://purl.uniprot.org/uniprot/Q62395 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in goblet cells of the intestines and colon (at protein level). Expressed abundantly in goblet cells of intestine and colon, and at low levels in stomach. No expression in brain, lung, spleen, kidney, uterus, pancreas, liver, heart or thymus.|||Involved in the maintenance and repair of the intestinal mucosa. Promotes the mobility of epithelial cells in healing processes (motogen).|||Mice lacking this gene show impaired mucosal healing after injury and die from extensive colitis after oral administration of dextran sulfate.|||Monomer. Homodimer; disulfide-linked.|||No expression found in embryos.|||extracellular matrix http://togogenome.org/gene/10090:Or4x13 ^@ http://purl.uniprot.org/uniprot/A0A1L1SQ02 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dbf4 ^@ http://purl.uniprot.org/uniprot/Q9QZ41 ^@ Function|||Induction|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Forms a complex with CDC7. Note that CDC7 forms distinct complex either with DBF4A or DBF4B. Such complexes are stable upon replication stress. Interacts with MEN1, MCM2, ORC2, ORC4 and ORC6. Interacts (via IBM motifs) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (By similarity).|||In a cell cycle-dependent manner. Induced at low level through G1. Increased during S phase and decreased at the end of S phase.|||Nucleus|||Phosphorylation increases its interaction with PSIP1.|||Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role DNA in replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. http://togogenome.org/gene/10090:Chst9 ^@ http://purl.uniprot.org/uniprot/Q76EC5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 2 family.|||Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Participates in biosynthesis of glycoprotein hormones lutropin and thyrotropin, by mediating sulfation of their carbohydrate structures. Has a higher activity toward carbonic anhydrase VI than toward lutropin. Only active against terminal GalNAcbeta1,GalNAcbeta.|||Golgi apparatus membrane|||Highly expressed in kidney and pituitary gland. http://togogenome.org/gene/10090:Xcr1 ^@ http://purl.uniprot.org/uniprot/Q544D8|||http://purl.uniprot.org/uniprot/S4R1K3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane http://togogenome.org/gene/10090:Ddx39a ^@ http://purl.uniprot.org/uniprot/Q8VDW0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DECD subfamily.|||Binds ALYREF/THOC4 and DDX39B/BAT1 (By similarity). Interacts with SARNP (By similarity). Interacts with MX1 (By similarity). Interacts with MCM3AP (By similarity).|||Cytoplasm|||Involved in pre-mRNA splicing. Required for the export of mRNA out of the nucleus (By similarity).|||Nucleus http://togogenome.org/gene/10090:Polr3c ^@ http://purl.uniprot.org/uniprot/B2RX77|||http://purl.uniprot.org/uniprot/Q9D483 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic RPC3/POLR3C RNA polymerase subunit family.|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits (By similarity). RPC3/POLR3C, RPC6/POLR3F and RPC7/POLR3G form a Pol III subcomplex (By similarity). Directly interacts with POLR3G and POLR3GL. Directly interacts with POLR3F/RPC39. Interacts with GTF3C4. As part of the RNA polymerase III (Pol III) complex, interacts with PKP2 (By similarity).|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. May direct with other members of the subcomplex RNA Pol III binding to the TFIIIB-DNA complex via the interactions between TFIIIB and POLR3F. May be involved either in the recruitment and stabilization of the subcomplex within RNA polymerase III, or in stimulating catalytic functions of other subunits during initiation. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF-Kappa-B through the RIG-I pathway. Preferentially binds single-stranded DNA (ssDNA) in a sequence-independent manner.|||Nucleus http://togogenome.org/gene/10090:Tdrkh ^@ http://purl.uniprot.org/uniprot/Q80VL1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Tdrkh family.|||Cytoplasm|||Highly expressed in testis, present at lower level in brain. Weakly or not expressed in other tissues (at protein level).|||Interacts with (symmetrically methylated) PIWIL1, PIWIL2 and PIWIL4.|||Male mice are sterile due to defects in male meiosis, piRNA production defects, DNA demethylation of LINE-1 (L1) transposable elements and an increase in L1 expression in the adult testis. Mutants have severely reduced levels of mature piRNAs and accumulate 1'U-containing, 2'O-methylated 31-37 nt RNAs that complement the missing mature piRNAs.|||Mitochondrion|||Participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Required for the final steps of primary piRNA biogenesis by participating in the processing of 31-37 nt intermediates into mature piRNAs. May act in pi-bodies and piP-bodies by transferring piRNA precursors or intermediates to or between these granules.|||Present at low level in male gonads in postnatal day 7 (P7) Expressed at higher level in P14, P21 and adult testes, correlating with the onset of meiosis (at protein level). Expressed in spermatogonia, spermatocytes and round spermatids, but not in elongating spermatids.|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Bag4 ^@ http://purl.uniprot.org/uniprot/Q8CI61 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds to the ATPase domain of HSP/HSC70 chaperones. Binds to the death domain of TNFRSF12 (By similarity). Binds to the death domain of TNFRSF1A in the absence of TNF and thereby prevents binding of adapter molecules such as TRADD or TRAF2. Interacts with PRKN (By similarity).|||Cytoplasm|||Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Prevents constitutive TNFRSF1A signaling (By similarity). Negative regulator of PRKN translocation to damaged mitochondria (By similarity). http://togogenome.org/gene/10090:Zdhhc5 ^@ http://purl.uniprot.org/uniprot/Q8VDZ4 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autopalmitoylated (By similarity). Palmitoylation of the C-terminal tail regulates stimulation-dependent plasma membrane motility (By similarity).|||Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.|||Cell membrane|||Deletion mutant mice are born at half the expected rate, and survivors show a marked deficit in contextual fear conditioning, an indicator of defective hippocampal-dependent learning (PubMed:20178993). Loss of ZDHHC5 in oligodendrocytes inhibits myelination and reduces the expression levels of myelin-related and anti-apoptosis genes (PubMed:34724258).|||Highly enriched in brain, detectable in liver and heart, and undetectable in most other tissues.|||In neural stem cells, rapid up-regulation by EGF, combined with FGF2 and heparin.|||In neural stem cells, rapidly degraded through the proteasome pathway following growth factors withdrawal, a strategy used to induce differentiation.|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, fatty acid uptake, bacterial sensing or cardiac functions (PubMed:21820437, PubMed:22081607). Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:24562000). Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins. Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2. Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2. Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes. Participates also in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:30605677). Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis. Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (PubMed:34724258).|||Phosphorylation regulates association with endocytic proteins and its subcellular localization. Phosphorylation by LYN during fatty acid uptake leads to inactivation of the activity.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Slfnl1 ^@ http://purl.uniprot.org/uniprot/Q8BHW9 ^@ Similarity ^@ Belongs to the Schlafen family. Subgroup I subfamily. http://togogenome.org/gene/10090:Crhr1 ^@ http://purl.uniprot.org/uniprot/K9J9G1|||http://purl.uniprot.org/uniprot/P35347|||http://purl.uniprot.org/uniprot/Q0VGH2|||http://purl.uniprot.org/uniprot/Q3ZAT0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||C-terminal Ser or Thr residues may be phosphorylated.|||Cell membrane|||Detected in brain cortex (at protein level).|||Endosome|||G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.|||Heterodimer; heterodimerizes with GPER1 (By similarity). Interacts (via N-terminal extracellular domain) with CRH and UCN. Interacts with DLG1; this inhibits endocytosis of CRHR1 after agonist binding.|||Heterozygous mice are fertile and produce homozygous pups at the expected Mendelian rate, but about 15% of the homozygous males die between 3 and 12 weeks after birth. Mice are deficient in CRF-mediated secretion of ACTH and show no increase in intracellular cAMP levels in response to CRF. Mice display a marked decrease in the size of the zona fasciculata of the adrenal gland, where corticosterone is produced, and have very low plasma corticosterone levels. Mutant mice display reduced anxiety. They fail to produce increased levels of ACTH and corticosterone in response to stress, contrary to wild type mice. Homozygous mice are fertile, but almost all of the pups die within 48 hours after birth, due to defects in lung inflation and alveolar collapse. Treatment of pregnant females with corticosterone-containing drinking water results in normal lung maturation and normal survival of their progeny.|||Membrane|||Phosphorylation at Ser-301 by PKA prevents maximal coupling to Gq-protein, and thereby negatively regulates downstream signaling.|||The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure (By similarity). http://togogenome.org/gene/10090:Sh3bgr ^@ http://purl.uniprot.org/uniprot/Q9WUZ7 ^@ Similarity ^@ Belongs to the SH3BGR family. http://togogenome.org/gene/10090:Zfp592 ^@ http://purl.uniprot.org/uniprot/Q52KI9|||http://purl.uniprot.org/uniprot/Q8BHZ4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in the brain.|||Expressed in the embryo at least from 10 dpc until birth.|||Interacts with ZMYND8.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Or51f2 ^@ http://purl.uniprot.org/uniprot/E9Q554 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nfxl1 ^@ http://purl.uniprot.org/uniprot/E9Q8I7 ^@ Similarity ^@ Belongs to the NFX1 family. http://togogenome.org/gene/10090:Alkbh3 ^@ http://purl.uniprot.org/uniprot/Q8K1E6 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by ascorbate.|||Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||Detected in testis, kidney, liver and heart.|||Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A) (By similarity). Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:16174769). Has a strong preference for single-stranded DNA (PubMed:16174769). Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3. Can repair exocyclic 3,N4-ethenocytosine adducs in single-stranded DNA. Also acts on RNA. Demethylates N(1)-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5'-untranslated regions (UTRs) and in the vicinity of start codons. Requires molecular oxygen, alpha-ketoglutarate and iron (By similarity).|||Interacts with the ASCC complex composed of ASCC1, ASCC2 and ASCC3. Interacts directly with ASCC3, and is thereby recruited to the ASCC complex. Interacts with OTUD4; the interaction is direct. Interacts with USP7 and USP9X.|||No visible phenotype.|||Nucleus|||Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination. OTUD4 promotes USP7 and USP9X-dependent deubiquitination of 'Lys-48'-polyubiquitinated ALKBH3 promoting the repair of alkylated DNA lesions. http://togogenome.org/gene/10090:Trpc7 ^@ http://purl.uniprot.org/uniprot/E9PVJ9|||http://purl.uniprot.org/uniprot/Q0VFY2|||http://purl.uniprot.org/uniprot/Q3UXW9|||http://purl.uniprot.org/uniprot/Q9WVC5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC7 sub-subfamily.|||Cell membrane|||Interacts with MX1 and RNF24. Interacts (via ANK-repeat domains) with PRKG1.|||Membrane|||Nucleus envelope|||Phosphorylation by PRKG1 at Thr-15 negatively regulates TRPC7 activity.|||Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG). May also be activated by intracellular calcium store depletion. http://togogenome.org/gene/10090:Nell1 ^@ http://purl.uniprot.org/uniprot/Q2VWQ2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homotrimer. Binds to PKC beta-1. Interacts with ATRAID; the interaction promotes osteoblast cell differentiation and mineralization (By similarity).|||Nucleus envelope|||Plays a role in the control of cell growth and differentiation. Promotes osteoblast cell differentiation and terminal mineralization.|||Secreted http://togogenome.org/gene/10090:1110017D15Rik ^@ http://purl.uniprot.org/uniprot/Q2MH31 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPMIP6 family.|||Cytoplasm|||Deficient mice are viable and have normal fertility.|||During male germ cell development, expression of isoform 1 begins at day 21, increases after day 30 and continues to increase in the adult. Expressed in elongating spermatids from steps 9-12 (at protein level). Expression in the lung increases at 16 dpc.|||Expressed in both lung and testis.|||Interacts with alpha-tubulin.|||May participate in intramanchette transport and midpiece formation of the sperm tail (PubMed:31504408). May play a potential role in somatic cell proliferation (PubMed:31504408).|||Mitochondrion|||Nucleus|||Testis-specific, expressed exclusively in germ cells (at protein level).|||Testis-specific.|||Up-regulated during cilia assembly in IMCD3 cells.|||cytoskeleton|||flagellum http://togogenome.org/gene/10090:Leng8 ^@ http://purl.uniprot.org/uniprot/Q8CBY3 ^@ Subunit ^@ May be part of a SEM1-containing complex. http://togogenome.org/gene/10090:Sebox ^@ http://purl.uniprot.org/uniprot/P70368 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||Expressed in brain, skin, ovary and liver. Also expressed in maturing oocytes, eggs, zygotes and 2-cell embryos, but not 4-cell embryos.|||Expressed in embryos from day 7. Expression is low in 12 day embryos and higher in 18 and 19 day embryos.|||Nucleus|||Probable transcription factor involved in the control of specification of mesoderm and endoderm. http://togogenome.org/gene/10090:Vmn1r180 ^@ http://purl.uniprot.org/uniprot/B9EK86 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kif6 ^@ http://purl.uniprot.org/uniprot/E9PX57 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. http://togogenome.org/gene/10090:Zfp661 ^@ http://purl.uniprot.org/uniprot/Q8BIQ3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Galk1 ^@ http://purl.uniprot.org/uniprot/Q9CXZ9|||http://purl.uniprot.org/uniprot/Q9R0N0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the GHMP kinase family. GalK subfamily.|||Catalyzes the transfer of a phosphate from ATP to alpha-D-galactose and participates in the first committed step in the catabolism of galactose.|||Homodimer. http://togogenome.org/gene/10090:Ifitm1 ^@ http://purl.uniprot.org/uniprot/Q9D103 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD225/Dispanin family.|||Cell membrane|||IFN-induced antiviral protein which inhibits the entry of viruses to the host cell cytoplasm, permitting endocytosis, but preventing subsequent viral fusion and release of viral contents into the cytosol. Active against multiple viruses, including influenza A virus, SARS coronavirus (SARS-CoV), Marburg virus (MARV), Ebola virus (EBOV), Dengue virus (DNV) and West Nile virus (WNV). Can inhibit: influenza virus hemagglutinin protein-mediated viral entry, MARV and EBOV GP1,2-mediated viral entry and SARS-CoV S protein-mediated viral entry. Also implicated in cell adhesion and control of cell growth and migration. Plays a key role in the antiproliferative action of IFN-gamma either by inhibiting the ERK activation or by arresting cell growth in G1 phase in a p53-dependent manner. Acts as a positive regulator of osteoblast differentiation.|||In migrating PGCs, expression is first detected during germ cell differentiation.|||Interacts with CD81. Part of a complex composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of mature B-cells. Interacts with CAV1; this interaction enhances the ability of CAV1 in inhibiting ERK activation.|||It has been previously shown that mediates migration of early primordial germ cells (PGCs) (PubMed:16326387). But according to PubMed:16326387, have no detectable effects on development of the germ line or on the generation of live young, hence, is not essential for PGC migration.|||Lysosome membrane|||Palmitoylation on membrane-proximal cysteines controls clustering in membrane compartments and antiviral activity.|||Predominantly expressed in nascent primordial germ cells, as well as in gonadal germ cells. http://togogenome.org/gene/10090:Cant1 ^@ http://purl.uniprot.org/uniprot/Q8VCF1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the apyrase family.|||Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > IDP >> UTP > CDP = GTP = ITP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP. Involved in proteoglycan synthesis.|||Endoplasmic reticulum membrane|||Golgi stack membrane|||Monomer. Homodimer; dimerization is Ca(2+)-dependent. http://togogenome.org/gene/10090:Has3 ^@ http://purl.uniprot.org/uniprot/O08650 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NodC/HAS family.|||Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of three isoenzymes responsible for cellular hyaluronan synthesis.|||Cell membrane|||Cytoplasmic vesicle|||Deficient mice are viable and fertile however absence of HAS3 increases the excitability of neural networks and drives the formation of epileptic seizures.|||Expressed at 17.5 dpc.|||Golgi apparatus membrane|||O-GlcNAcylation increases the hyaluronan synthase activity, HAS3 stability and its plasma membrane residence. The concentration of UDP-GlcNAc controls the level of O-GlcNAc modification.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Saa4 ^@ http://purl.uniprot.org/uniprot/P31532 ^@ Caution|||Disease Annotation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apolipoprotein of the HDL complex.|||Belongs to the SAA family.|||Expressed by the liver; secreted in plasma.|||Major acute phase reactant.|||Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function.|||SAA4 used to be called SAA5. What was SAA4 is a pseudogene which is now called SAA-ps.|||Secreted|||Upon cytokine stimulation. http://togogenome.org/gene/10090:H2al1g ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:Psrc1 ^@ http://purl.uniprot.org/uniprot/Q9D0P7 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PSRC1 family.|||Cytoplasm|||Highly expressed in heart, brain and lung. Weaker expression in kidney and testis.|||Induced by adriamycin and mitomycin C, in a p53-dependent manner, in NIH3T3 cells. This induction is inhibited by actinomycin D. Also induced by cisplatin in a p73-dependent manner in embryonic cells.|||Interacts with APC2 (PubMed:17310996). Interacts with KIF2A (By similarity). Interacts with ANKRD53; recruits ANKRD53 to the spindle during mitosis (By similarity).|||Phosphorylated during mitosis.|||Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate, and for normal rate of chromosomal segregation during anaphase. Plays a role in the regulation of mitotic spindle dynamics. Increases the rate of turnover of microtubules on metaphase spindles, and contributes to the generation of normal tension across sister kinetochores. Recruits KIF2A and ANKRD53 to the mitotic spindle and spindle poles. May participate in p53/TP53-regulated growth suppression (By similarity).|||spindle|||spindle pole http://togogenome.org/gene/10090:Ap5m1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0K9|||http://purl.uniprot.org/uniprot/Q8BJ63 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.|||Belongs to the adaptor complexes medium subunit family.|||Endosome membrane|||Late endosome membrane|||Lysosome membrane|||May be due to intron retention.|||Membrane|||Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1.|||Widely expressed, including in small intestine and testis. In small intestine, highly expressed in cytoplasm of villi epithelial cells and internal glands. In testis, selectively expressed in maturing sperm cells (at protein level).|||cytosol http://togogenome.org/gene/10090:Slc14a2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J213|||http://purl.uniprot.org/uniprot/A0A494BAL3|||http://purl.uniprot.org/uniprot/G5E849|||http://purl.uniprot.org/uniprot/Q8BMD1|||http://purl.uniprot.org/uniprot/Q8R4T9 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the urea transporter family.|||Cell membrane|||Expressed in the kidney medulla.|||Expressed in the peritubular myoid cells forming the outermost layer of the seminiferous tubules within the testes and is not detected in kidney (PubMed:11029290). Expression levels are coordinated with the stage of testes development and increase 15 days postpartum, commensurate with the start of seminiferous tubule fluid movement (PubMed:11029290).|||Highly expressed in kidney medulla (at protein level) (PubMed:12217874). Also detected in testes, heart, brain and liver (at protein level) (PubMed:12217874). In the kidney, present in thin descending limbs of the loop of Henle and in the middle and terminal inner medullary collecting ducts.|||Inhibited by phloretin (PubMed:11029290). Activated by forskolin, 3-isobutyl-1-methylxanthine (IBMX) and cAMP (PubMed:12217874).|||Inhibited by phloretin (PubMed:12217874). Activated by forskolin, 3-isobutyl-1-methylxanthine (IBMX) and cAMP (PubMed:12217874).|||Inhibited by phloretin.|||It is uncertain whether Met-1 or Met-10 is the initiator.|||Mediates the transport of urea driven by a concentration gradient across the cell membrane (PubMed:11029290). Implicated in the urea movement across the blood-testis barrier and does not translocate water (PubMed:11029290).|||Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism.|||Membrane http://togogenome.org/gene/10090:Or8d1 ^@ http://purl.uniprot.org/uniprot/Q7TRB7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Smpdl3b ^@ http://purl.uniprot.org/uniprot/P58242|||http://purl.uniprot.org/uniprot/Q3TLX9 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the acid sphingomyelinase family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 2 Zn(2+) per subunit.|||Cell membrane|||Interacts with TLR4, TLR7, TLR8 and TLR9.|||Lipid-modulating phosphodiesterase. Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity (PubMed:26095358). Acts as a negative regulator of Toll-like receptor signaling (PubMed:26095358, PubMed:27687724). Has in vitro phosphodiesterase activity, but the physiological substrate is unknown (PubMed:26095358, PubMed:27687724). Lacks activity with phosphocholine-containing lipids, but can cleave CDP-choline, and can release phosphate from ATP and ADP (in vitro) (PubMed:27687724).|||Macrophages and dendritic cells.|||Mice display higher inflammatory responses in models of TLR-dependent peritonitis. Macrophages show enhanced responsiveness to TLR stimulation and a significant change in membrane fluidity and the global cellular lipid composition.|||N-glycosylated.|||Secreted|||Strongly up-regulated by TLR stimuli and interferon gamma. http://togogenome.org/gene/10090:Ube2e1 ^@ http://purl.uniprot.org/uniprot/P52482|||http://purl.uniprot.org/uniprot/Q541Z5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes the covalent attachment of ISG15 to other proteins. Mediates the selective degradation of short-lived and abnormal proteins. In vitro also catalyzes 'Lys-48'-linked polyubiquitination.|||Autoubiquitinated.|||Belongs to the ubiquitin-conjugating enzyme family.|||ISGylation suppresses ubiquitin E2 enzyme activity.|||Interacts with RNF14.|||Nucleus http://togogenome.org/gene/10090:Bicd1 ^@ http://purl.uniprot.org/uniprot/B2KG46|||http://purl.uniprot.org/uniprot/G3UXK5|||http://purl.uniprot.org/uniprot/Q8BR07 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BicD family.|||Due to intron retention.|||Expressed during embryonic development.|||Expressed in the brain, heart and skeletal muscle.|||Golgi apparatus|||Interacts with RAB6A. Interacts (via C-terminus) with RAB6B (GTP-bound); the interaction is direct (By similarity). Interacts with CLIP-115 and KIFC2.|||Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport by recruiting the dynein-dynactin motor complex. http://togogenome.org/gene/10090:Rpl27a ^@ http://purl.uniprot.org/uniprot/P14115 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL15 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||Hydroxylated on His-39 by MINA. http://togogenome.org/gene/10090:Rrp1b ^@ http://purl.uniprot.org/uniprot/Q91YK2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRP1 family.|||Chromosome|||Citrullinated by PADI4.|||Interacts with the transcriptional activator E2F1 (By similarity). Interacts with serine/threonine-protein phosphatase PP1 subunits PPP1CB and PPP1CC but not with PPP1CA (By similarity). Interacts with 60S ribosomal proteins RPL5 and RPL27, ribosomal processing protein RRP1/NNP1 and other nucleolar proteins including NOP2/NOL1 and FBL (By similarity). Also interacts with nucleolar protein NPM1/B23 (By similarity). Interacts with splicing factor SRSF1 and LUC7L3/CROP (By similarity). Interacts with GTPase activator SIPA1 (PubMed:18081427). Interacts with H1-10, NCL, PARP1, TRIM28 and YBX3 (By similarity).|||Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (By similarity). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (By similarity). Involved in regulation of mRNA splicing (PubMed:23604122). Inhibits SIPA1 GTPase activity (PubMed:18081427). Involved in regulating expression of extracellular matrix genes (PubMed:18081427). Associates with chromatin and may play a role in modulating chromatin structure (By similarity).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Exd1 ^@ http://purl.uniprot.org/uniprot/Q8CDF7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EXD1 family.|||Cytoplasm|||Homodimer (By similarity). Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs.|||Mice are viable and display normal fertility but show defective biogenesis of antisense piRNAs and activation of transposons. Reduced sequences generated by Piwil2 slicing, impaired biogenesis of Piwil4 piRNAs and derepressed LINE1 retrotransposons.|||RNA-binding component of the PET complex, a multiprotein complex required for the processing of piRNAs during spermatogenesis. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposable elements, preventing their mobilization, which is essential for the germline integrity (PubMed:26669262). The PET complex is required during the secondary piRNAs metabolic process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs. In the PET complex, EXD1 probably acts as an RNA adapter. EXD1 is an inactive exonuclease (By similarity).|||The 3'-5' exonuclease domain lacks the conserved Asp-Glu-Asp-Asp (DEDD) residues that coordinates divalent ions essential for exonuclease activity. http://togogenome.org/gene/10090:Zfp507 ^@ http://purl.uniprot.org/uniprot/Q6ZPY5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Rnf11 ^@ http://purl.uniprot.org/uniprot/Q9QYK7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acylation at both Gly-2 and Cys-4 is required for proper localization to the endosomes.|||Cytoplasm|||Early endosome|||Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of TNFAIP3 to RIPK1 after TNF stimulation. TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Recruits STAMBP to the E3 ubiquitin-ligase SMURF2 for ubiquitination, leading to its degradation by the 26S proteasome.|||Interacts (when phosphorylated) with 14-3-3. Interacts with the E3 ubiquitin-ligases NEDD4, ITCH, SMURF2 and WWP1 (By similarity). Also interacts with the E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2N, but neither with CDC34, nor with UBE2L3. Interacts with ZNF350, EPS15 and STAMBP (By similarity). After TNF stimulation, interacts with TAX1BP1, TNFAIP3 and RIPK1; these interactions are transient and they are lost after 1 hour of stimulation with TNF. Interacts with GGA1 (By similarity).|||Nucleus|||Phosphorylation by PKB/AKT1 may accelerate degradation by the proteasome.|||Recycling endosome|||The PPxY motif mediates interaction with NEDD4.|||Ubiquitinated in the presence of ITCH, SMURF2 and UBE2D1, as well as WWP1. http://togogenome.org/gene/10090:Tmem178 ^@ http://purl.uniprot.org/uniprot/Q9CZ16 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of osteoclast differentiation in basal and inflammatory conditions by regulating TNFSF11-induced Ca (2+) fluxes, thereby controlling the induction of NFATC1 (PubMed:26644563).|||Belongs to the TMEM178 family.|||Endoplasmic reticulum membrane|||Highly expressed in the bone and its expression increases during osteoclastogenesis.|||Interacts with STIM1.|||Mice are osteopenic and are more susceptible to inflammatory bone loss, owing to enhanced osteoclast formation. http://togogenome.org/gene/10090:Or4k40 ^@ http://purl.uniprot.org/uniprot/Q7TQY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defb28 ^@ http://purl.uniprot.org/uniprot/Q3V2L0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Prl5a1 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0X8|||http://purl.uniprot.org/uniprot/Q9JII2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Tbccd1 ^@ http://purl.uniprot.org/uniprot/Q640P7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TBCC family.|||Expressed in brain and testis (at protein level).|||Plays a role in the regulation of centrosome and Golgi apparatus positioning, with consequences on cell shape and cell migration.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Dgat2l6 ^@ http://purl.uniprot.org/uniprot/A2ADU8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the diacylglycerol acyltransferase family.|||Diglyceride acyltransferase that uses fatty acyl-CoA as substrate. Particularly active with oleate as a substrate. Has no wax synthase activity to produce wax esters.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Rhebl1 ^@ http://purl.uniprot.org/uniprot/Q9D8T3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rheb family.|||Binds GTP and exhibits intrinsic GTPase activity. May activate NF-kappa-B-mediated gene transcription. Promotes signal transduction through MTOR, activates RPS6KB1, and is a downstream target of the small GTPase-activating proteins TSC1 and TSC2 (By similarity).|||Cytoplasm|||Endomembrane system|||Interacts with MTOR. http://togogenome.org/gene/10090:Rad17 ^@ http://purl.uniprot.org/uniprot/Q3UYY2|||http://purl.uniprot.org/uniprot/Q6NXW6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rad17/RAD24 family.|||Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination (By similarity). Essential for embryonic development. May be involved in homologous recombination.|||Mice show numerous defects in embryonic development, starting at E8.5.|||Nucleus|||Part of a DNA-binding complex containing RFC2, RFC3, RFC4 and RFC5. Interacts with RAD1 and RAD9 within the RAD1-RAD9-HUS1 complex. Interacts with RAD9B, POLE, SNU13 and MCM7. DNA damage promotes interaction with ATR or ATM and disrupts interaction with the RAD1-RAD9-HUS1 complex (By similarity).|||Phosphorylated. Phosphorylation on Ser-647 and Ser-657 is cell cycle-regulated, enhanced by genotoxic stress, and required for activation of checkpoint signaling.|||Ubiquitous at low levels. Highly expressed in testis, where it is expressed in spermatogonia, spermatocytes and spermatids, but absent in mature spermatozoa (at protein level). http://togogenome.org/gene/10090:Nars2 ^@ http://purl.uniprot.org/uniprot/Q8BGV0 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Expressed in brain and inner ear, including the cochlear epithelium and organ of Corti.|||Homodimer.|||Mitochondrion|||Mitochondrion matrix http://togogenome.org/gene/10090:Nvl ^@ http://purl.uniprot.org/uniprot/Q9DBY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Interacts with NCL/nucleolin (PubMed:21474449). Isoform 1 and isoform 2 interact with TERT and isoform 1 exhibits a higher binding affinity for TERT compared to isoform 2. Isoform 1 interacts with MTREX in an ATP-dependent manner; the interaction is required to associate NVL with nuclear RNA exosome. Isoform 1 interacts with RPL5 in an ATP-dependent manner. Interacts with WDR74 (through WDR repeats); the interaction is independent of RNA or pre-60S ribosome particles (By similarity).|||Participates in the assembly of the telomerase holoenzyme and effecting of telomerase activity via its interaction with TERT. Involved in both early and late stages of the pre-rRNA processing pathways. Spatiotemporally regulates 60S ribosomal subunit biogenesis in the nucleolus. Catalyzes the release of specific assembly factors, such as WDR74, from pre-60S ribosomal particles through the ATPase activity.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Plcl1 ^@ http://purl.uniprot.org/uniprot/Q3USB7 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||In the PI-PLC X-box Asn-459 is present instead of the conserved His which is one of the active site residues. It is therefore expected that this protein lacks catalytic activity.|||Interacts with PPP2CA, Ins(1,4,5)P3, Ins(1,4,5,6)P4 GABARAP, GABA receptor beta subunits, GABA receptor gamma-2 subunits and PPP1C (By similarity). May form a ternary complex with GABA receptor beta subunit and GABARAP. The formation of a ternary complex with GABA receptor beta subunit and GABARAP could be the key step for facilitating the association of GABARAP with the GABA receptor gamma-2 subunit and to allow it to be transported at the right destination.|||Involved in an inositol phospholipid-based intracellular signaling cascade. Shows no PLC activity to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol. Component in the phospho-dependent endocytosis process of GABA A receptor. Acts as an inhibitor of PPP1C (By similarity). Involved in the assembly and/or the trafficking of gamma-2 subunit-containing GABA A receptors.|||Phosphorylated by the catalytic subunit of PKA. Phosphorylation of Thr-94 resulted in dissociation of PPP1C from PRIP1. http://togogenome.org/gene/10090:1700019N19Rik ^@ http://purl.uniprot.org/uniprot/Q9CQT6 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis (at protein level).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme. May serve to reinforce and thus stabilize the microtubule structure in the sperm flagella.|||Nucleus|||flagellum axoneme http://togogenome.org/gene/10090:Bcl2l13 ^@ http://purl.uniprot.org/uniprot/P59017 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Bcl-2 family.|||May promote the activation of caspase-3 and apoptosis.|||Mitochondrion membrane|||Monomer. http://togogenome.org/gene/10090:Nphs1 ^@ http://purl.uniprot.org/uniprot/Q9QZS7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily.|||Cell membrane|||Death by postnatal day 2 associated with proteinuria, edema and massive glomerular vascular leak. Kidneys display enlarged Bowman's spaces, dilated tubuli, effacement of podocyte foot processes and an absence of the glomerular epithelial slit diaphragm. Impaired skeletal muscle development characterized by incomplete myoblast fusion.|||Expressed in kidney glomeruli. In the embryo, expressed in the mesonephric kidney at 11 dpc with strong expression in cranial tubules with podocyte-like structures. Expression is observed in the podocytes of the developing kidney from 13 dpc. High expression is also detected in the developing cerebellum, hindbrain, spinal cord, retina and hypothalamus. Expressed in skeletal muscle during myoblast fusion such as in the adult following acute injury and in the embryo but not detected in uninjured adult skeletal muscle. Isoform 1 and isoform 2 are expressed in the newborn brain and developing cerebellum. Isoform 1 is the predominant isoform in adult kidney.|||Interacts with NPHS2 and with CD2AP (via C-terminal domain). Interacts with MAGI1 (via PDZ 2 and 3 domains) forming a tripartite complex with IGSF5/JAM4. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1 and SPTBN1 (By similarity). Interacts with DDN; the interaction is direct. Self-associates (via the Ig-like domains). Also interacts (via the Ig-like domains) with KIRREL1 and KIRREL2; the interaction with KIRREL1 is dependent on KIRREL1 glycosylation. Interacts with KIRREL3 (PubMed:15843475, PubMed:18752272). Interacts with phosphatidylinositol 3-kinase regulatory subunit PIK3R1; the interaction is reduced by high glucose levels (By similarity).|||Phosphorylated at Tyr-1208 by FYN, leading to the recruitment and activation of phospholipase C-gamma-1/PLCG1 (By similarity). Tyrosine phosphorylation is reduced by high glucose levels (By similarity). Dephosphorylated by tensin TNS2 which leads to reduced binding of NPHN1 to PIK3R1 (By similarity).|||Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoskeleton. Plays a role in skeletal muscle formation through regulation of myoblast fusion. http://togogenome.org/gene/10090:Polr3e ^@ http://purl.uniprot.org/uniprot/Q9CZT4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. Interacts with RPC4 (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific periphjeric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Essential for efficient transcription from both the type 2 VAI and type 3 U6 RNA polymerase III promoters. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity).|||Nucleus http://togogenome.org/gene/10090:Tagap ^@ http://purl.uniprot.org/uniprot/B2RWW0 ^@ Caution|||Developmental Stage|||Function|||Tissue Specificity ^@ Expressed in testis at 7 dpc.|||Highly expressed in testis.|||May function as a GTPase-activating protein. May play a role in transmission ratio distortion (TRD) in mouse, in which heterozygous males for t-locus transmit their t-carrying chromosome to 95% or more of their offspring.|||Previously thought to be the same gene as Tagap1. These are distinct loci that encode proteins with identical C-termini but each with a unique N-terminus. http://togogenome.org/gene/10090:Dnaaf6 ^@ http://purl.uniprot.org/uniprot/Q3KNI6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIH1 family.|||Cytoplasm|||Deficient mice develop normally but manifest male sterility. Sperm are immotile and fragile with the axoneme of the flagellum lacking outer dynein arms (ODAs) and inner dynein arms (IDAs) and showing a disturbed microtubules organization.|||Interacts with HSPA1A/B, HSP90AA1 and DNAI2 (PubMed:24421334). Interacts with DNAAF2 and DNAAF4 (By similarity).|||Plays a role in cytoplasmic pre-assembly of axonemal dynein.|||Specifically expressed in testis. Detected in pachytene spermatocytes from 5 weeks of age and in pachytene and diplotene spermatocytes of adult mice. Not detected in spermatids or mature sperm.|||trans-Golgi network http://togogenome.org/gene/10090:Or4f61 ^@ http://purl.uniprot.org/uniprot/A2AVL6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Snap25 ^@ http://purl.uniprot.org/uniprot/P60879 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type A (BoNT/A, botA) which hydrolyzes the 197-Gln-|-Arg-198 bond and inhibits neurotransmitter release (PubMed:8243676, PubMed:8103915).|||(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type E (BoNT/E) which hydrolyzes the 180-Arg-|-Ile-181 bond and inhibits neurotransmitter release (PubMed:8243676, PubMed:8103915).|||Belongs to the SNAP-25 family.|||Cell membrane|||Expressed in the outer nuclear layer of the retina (at protein level).|||Palmitoylated. Cys-85 appears to be the main site, and palmitoylation is required for membrane association.|||Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A; this complex constitutes the basic catalytic machinery of the complex neurotransmitter release apparatus (PubMed:19196426, PubMed:28821673). Recruited to the SNARE complex following binding of the SNARE complex component STX1A to STXBP1 (PubMed:28821673). This complex binds CPLX1 (PubMed:19196426). Found in a complex containing SYT1, SV2B and STX1A (PubMed:15466855). Found in a ternary complex with STX1A and VAMP8 (PubMed:9731768). Interacts with HSC70 and with SYT9, forming a complex with DNAJC5 (PubMed:20847230). The interaction with SYT9 is inhibited in presence of calcium (PubMed:20847230). Isoform 1 and isoform 2 interact with BLOC1S6 (PubMed:19546860). Interacts with CENPF (PubMed:16672379). Interacts with EQTN (PubMed:19285662). Interacts with HGS (By similarity). Interacts with KCNB1 (via N-terminus); reduces the voltage-dependent potassium channel KCNB1 activity in pancreatic beta cells (By similarity). Interacts with OTOF (PubMed:17055430). Interacts with RIMS1 (By similarity). Interacts with SNAPIN (PubMed:10195194). Interacts with STXBP6 (By similarity). Interacts with TRIM9 (By similarity). Interacts with ZDHHC13 (via ANK repeats) (PubMed:25253725). Interacts with ZDHHC17 (via ANK repeats) (PubMed:25253725). Associates with the BLOC-1 complex (PubMed:19546860). Interacts with PLCL1 (via C2 domain) (PubMed:23341457). Interacts with PRRT2; this interaction may impair the formation of the SNARE complex (PubMed:22832103, PubMed:27052163, PubMed:29056747). Interacts with alpha-synuclein/SNCA (PubMed:20798282). Interacts with PRPH2 (PubMed:26406599). Interacts with ROM1 (PubMed:26406599). Interacts with STX3 isoform 3B (PubMed:26406599).|||Photoreceptor inner segment|||perinuclear region|||synaptosome|||t-SNARE involved in the molecular regulation of neurotransmitter release (PubMed:8243676, PubMed:8103915). May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF (PubMed:16672379). Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells (By similarity). http://togogenome.org/gene/10090:Tmem132d ^@ http://purl.uniprot.org/uniprot/A0A0R4J0I2|||http://purl.uniprot.org/uniprot/Q76HP3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM132 family.|||Expressed in mature oligodendrocytes in the white and gray matter of the brain.|||May serve as a cell-surface marker for oligodendrocyte differentiation.|||Membrane http://togogenome.org/gene/10090:Rmi1 ^@ http://purl.uniprot.org/uniprot/Q9D4G9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RMI1 family.|||Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM. Directly interacts with RMI2 and TOP3A. May bind DHJ. Interacts (via N-terminal region) with BLM; the interaction is direct (By similarity).|||Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or10ag59 ^@ http://purl.uniprot.org/uniprot/A2AV41 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5ak23 ^@ http://purl.uniprot.org/uniprot/Q8VF75 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nbl1 ^@ http://purl.uniprot.org/uniprot/Q61477 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DAN family.|||Homodimer.|||Possible candidate as a tumor suppressor gene of neuroblastoma. May play an important role in preventing cells from entering the final stage (G1/S) of the transformation process.|||Secreted http://togogenome.org/gene/10090:Cd4 ^@ http://purl.uniprot.org/uniprot/P06332|||http://purl.uniprot.org/uniprot/Q3TSV7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Forms disulfide-linked homodimers at the cell surface. Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI. Interacts with IL16; this interaction induces a CD4-dependent signaling in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha chain (via alpha-2 domain) and beta chain (via beta-2 domain); this interaction increases the affinity of TCR for peptide-MHCII. CD4 oligomerization via Ig-like C2-type 2 and 3 domains appears to be required for stable binding to MHCII and adhesion between T cells and APCs.|||Highly expressed in T-helper cells. The presence of CD4 is a hallmark of T-helper cells which are specialized in the activation and growth of cytotoxic T-cells, regulation of B cells, or activation of phagocytes. CD4 is also present in other immune cells such as macrophages, dendritic cells or NK cells.|||Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages.|||Mice lacking Cd4 display markedly decreased T-helper cell activity.|||Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.|||Phosphorylated by PKC; phosphorylation plays an important role for CD4 internalization.|||The Ig-like V-type domain mediates the interaction with MHCII. http://togogenome.org/gene/10090:Nutm1 ^@ http://purl.uniprot.org/uniprot/Q8BHP2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NUT family.|||Cytoplasm|||Methylated at Gln-1042 by N6AMT1.|||Nucleus|||Phosphorylation on Ser-1022, Ser-1025 or Ser-1027 is important for cytoplasmic export.|||Plays a role in the regulation of proliferation. Regulates TERT expression by modulating SP1 binding to TERT promoter binding sites. http://togogenome.org/gene/10090:Gm3286 ^@ http://purl.uniprot.org/uniprot/Q3UL33 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Tril ^@ http://purl.uniprot.org/uniprot/Q9DBY4 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, MD-2 and TLR4. Interacts with TLR4; this interaction is greatly enhanced by LPS stimulation (By similarity). Interacts with LPS (By similarity).|||By bacterial lipopolysaccharides (LPS) (in vivo and in vitro).|||Component of the TLR4 signaling complex. Mediates the innate immune response to bacterial lipopolysaccharide (LPS) leading to cytokine secretion (By similarity).|||Highly expressed in brain, spinal cord and lung.|||Membrane|||N-glycolysaled. http://togogenome.org/gene/10090:Nme6 ^@ http://purl.uniprot.org/uniprot/O88425 ^@ Function|||Similarity ^@ Belongs to the NDK family.|||Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. http://togogenome.org/gene/10090:Pilrb2 ^@ http://purl.uniprot.org/uniprot/Q2YFS1 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRB2 is probably a cellular signaling activating receptor that associates with ITAM-bearing adapter molecules on the cell surface. http://togogenome.org/gene/10090:Hsd3b8 ^@ http://purl.uniprot.org/uniprot/Q3UIU9|||http://purl.uniprot.org/uniprot/Q61767 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Expression between 15-20 days post-implantation occurs only in the kidney of the male fetus and not in the female, whereas a similar expression is found in adult male and female kidneys.|||Kidney (at protein level); found only in the cortex, appears to be associated with the proximal tubules; and a minor expression in testis.|||Mitochondrion membrane|||Responsible for the reduction of the oxo group on the C-3 of 5alpha-androstane steroids. Catalyzes the conversion of dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Does not function as an isomerase. http://togogenome.org/gene/10090:Kbtbd13 ^@ http://purl.uniprot.org/uniprot/Q8C828 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||Component of the BCR(KBTBD13) E3 ubiquitin ligase complex, at least composed of CUL3 and KBTBD13 and RBX1. Interacts with CUL3 (By similarity).|||Cytoplasm|||Expressed in skeletal muscle, heart and lung.|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex.|||The BCB domain mediates the interaction with CUL3. http://togogenome.org/gene/10090:Clpx ^@ http://purl.uniprot.org/uniprot/Q6P8N8|||http://purl.uniprot.org/uniprot/Q8C4Z5|||http://purl.uniprot.org/uniprot/Q9JHS4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP. Targets specific substrates for degradation by the Clp complex. Can perform chaperone functions in the absence of CLPP. Enhances the DNA-binding activity of TFAM and is required for maintaining a normal mitochondrial nucleoid structure (PubMed:10347188). ATP-dependent unfoldase that stimulates the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis. Important for efficient erythropoiesis through up-regulation of heme biosynthesis (By similarity).|||Belongs to the ClpX chaperone family.|||Detected in liver (at protein level).|||Homohexamer that forms a ring structure; this hexamerization requires ATP binding. Component of the Clp complex formed by the assembly of two CLPP heptameric rings with two CLPX hexameric rings, giving rise to a symmetrical structure with two central CLPP rings flanked by a CLPX ring at either end of the complex (PubMed:22710082). Interacts with TFAM (By similarity).|||Mitochondrion|||mitochondrion nucleoid http://togogenome.org/gene/10090:Agt ^@ http://purl.uniprot.org/uniprot/Q3UTR7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.|||Secreted|||Stimulates aldosterone release. http://togogenome.org/gene/10090:Ces2f ^@ http://purl.uniprot.org/uniprot/Q08ED5 ^@ Similarity ^@ Belongs to the type-B carboxylesterase/lipase family. http://togogenome.org/gene/10090:Ccdc116 ^@ http://purl.uniprot.org/uniprot/Q80X53 ^@ Subcellular Location Annotation ^@ centrosome http://togogenome.org/gene/10090:Lce1m ^@ http://purl.uniprot.org/uniprot/Q9CR91 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Rnf167 ^@ http://purl.uniprot.org/uniprot/Q91XF4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Autoubiquitinated in vitro in the presence of UBE2D1 and UBE2E1.|||Belongs to the Godzilla family.|||Cell membrane|||E3 ubiquitin-protein ligase that acts as a regulator of the TORC1 signaling pathway. Positively regulates the TORC1 signaling pathway independently of arginine levels: acts by catalyzing 'Lys-29'-polyubiquitination and degradation of CASTOR1, releasing the GATOR2 complex from CASTOR1. Also negatively regulates the TORC1 signaling pathway in response to leucine deprivation: acts by mediating 'Lys-63'-linked polyubiquitination of SESN2, promoting SESN2-interaction with the GATOR2 complex. Also involved in protein trafficking and localization. Acts as a regulator of synaptic transmission by mediating ubiquitination and degradation of AMPAR receptor GluA2/GRIA2. Does not catalyze ubiquitination of GluA1/GRIA1. Also acts as a regulator of the recycling endosome pathway by mediating ubiquitination of VAMP3. Regulates lysosome positioning by catalyzing ubiquitination and degradation of ARL8B. Plays a role in growth regulation involved in G1/S transition by mediating, possibly by mediating ubiquitination of SLC22A18. Acts with a limited set of E2 enzymes, such as UBE2D1 and UBE2N.|||Endomembrane system|||Endosome membrane|||Lysosome membrane http://togogenome.org/gene/10090:Stap2 ^@ http://purl.uniprot.org/uniprot/Q8R0L1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with PTK6 and CSF1R.|||Membrane|||Phosphorylated on tyrosine. Phosphorylated by PTK6 at Tyr-250 modulates PTK6-mediated STAT3 activation.|||Substrate of protein kinase PTK6 (By similarity). May play a regulatory role in the acute-phase response in systemic inflammation and may modulate STAT3 activity.|||Widely expressed. http://togogenome.org/gene/10090:Sox11 ^@ http://purl.uniprot.org/uniprot/Q7M6Y2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expression detected from 8.5 dpc through to 13.5 dpc, with a considerable increase in expression apparent at 13.5 dpc (PubMed:9337129, PubMed:18505825, PubMed:20596238). Expressed throughout the central and peripheral nervous system, as well as the mesenchyme of many developing organs between 12.5 dpc and 14.5 dpc (PubMed:18403418). Abundantly expressed in the developing cerebral cortex, thalamus, hippocampus, cerebellar cortex, and ganglia in the brain at 14.5 dpc and 16.5 dpc with low expression at 18.5 dpc (PubMed:18505825). Abundantly expressed in the gut epithelium at 14.5 dpc (PubMed:18505825). Abundantly expressed in the olfactory epithelium with low expression in skin, spinal cord, kidney, heart, muscle, cartilage from 14.5 dpc to 18.5 dpc (PubMed:18505825). Very low expression in intestine and lung, with no expression detectable at 18.5 dpc (PubMed:18505825). Abundantly expressed in the subventricular zone of the brain at 18.5 dpc (PubMed:18505825). Expressed in the brain at postnatal day 2 (PubMed:18403418).|||Expression prominent in the periventricular cells of the central nervous system, also observed in a wide range of tissues involved in epithelial-mesenchymal interactions.|||Mice die at birth with numerous morphological abnormalities (PubMed:20596238). Incomplete separation of the heart ventricles with fused aorta and pulmonary arteries (PubMed:20596238). Skeletal malformations including hypoplastic sternebrae, unfused vertebral bodies and hypomineralized skull (PubMed:20596238). All mice have microphthalmia and open eyelids, with 50% of mice exhibiting omphalocele, and 40% exhibiting cleft palate, cleft lips and a tail kink (PubMed:20596238). Sox11 and Sox4 double knockout mice die in utero at 10.5 dpc (PubMed:20596238). Embryos are small and unturned with developmental defects such as failure of heart primordia fusion, a thin and undulated neural tube, failure of limb budding and somite formation, suggesting developmental arrest at 8.5 dpc (PubMed:20596238). Embryos showed reduced cell proliferation and increased cell death in the neural tube, branchial arches, somites and reduced expression of Tead2 at 9.5 dpc (PubMed:20596238). Sox4, Sox11, and Sox12 triple knockout mice show severe thinning and undulation of the neural tube (PubMed:20596238).|||Nucleus|||Transcription factor that acts as a transcriptional activator (PubMed:18505825, PubMed:18403418). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation (PubMed:18505825, PubMed:18403418). Acts as a transcriptional activator of TEAD2 by binding to its gene promoter and first intron (PubMed:20596238). Plays a redundant role with SOX4 and SOX12 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis (PubMed:20596238). http://togogenome.org/gene/10090:Pax7 ^@ http://purl.uniprot.org/uniprot/G3UX36|||http://purl.uniprot.org/uniprot/P47239 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the paired homeobox family.|||Can bind to DNA as a heterodimer with PAX3. Interacts with DAXX (By similarity). Interacts with PAXBP1; the interaction links PAX7 to a WDR5-containing histone methyltransferase complex (PubMed:22862948).|||Expressed specifically during the development of the nervous and muscular system.|||Nucleus|||Transcription factor that is involved in the regulation of muscle stem cells proliferation, playing a role in myogenesis and muscle regeneration. http://togogenome.org/gene/10090:Ttll11 ^@ http://purl.uniprot.org/uniprot/A4Q9F4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tubulin--tyrosine ligase family.|||Gln-252 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in brain, kidney, liver, lung, muscle and testis (PubMed:17499049). Expressed in heart, spleen and trachea (PubMed:17499049). In the brain, expressed in ependymal cilia, cortex, corpus callosum and striatum (PubMed:23897886).|||Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin (PubMed:17499049, PubMed:20530212). Preferentially mediates ATP-dependent polyglutamate long side-chain elongation over the initiation step of the polyglutamylation reaction (PubMed:17499049, PubMed:20530212). Preferentially modifies the alpha-tubulin tail over a beta-tail (PubMed:17499049). Required for CCSAP localization to both spindle and cilia microtubules (By similarity). Promotes tubulin polyglutamylation which stimulates spastin/SPAST-mediated microtubule severing, thereby regulating microtubule functions (PubMed:20530212).|||The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Cd14 ^@ http://purl.uniprot.org/uniprot/P10810|||http://purl.uniprot.org/uniprot/Q3UB18|||http://purl.uniprot.org/uniprot/Q3UE54|||http://purl.uniprot.org/uniprot/Q4FJP7 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (By similarity). Interacts with LPS-bound LPB. Interacts with LPAR1 (PubMed:21821728). Interacts with the TLR2:TLR6 or TLR2:TLR1 heterodimers; upon interaction with ligands such as diacylated lipopeptides and triacylated lipopeptides, respectively. Interacts with MYO18A (By similarity). Interacts with FSTL1 (By similarity).|||Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Interacts with LPAR1.|||Cell membrane|||Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:16148141). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:8612135, PubMed:15895089). Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway (By similarity). Acts as an accessory receptor for M.tuberculosis lipoproteins LprA, LprG and LpqH, in conjunction with coreceptors TLR2 and TLR1. The lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (By similarity).|||Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-).|||Detected on peritoneal macrophages (at protein level) (PubMed:8612135). Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and lung macrophages (at protein level) (PubMed:19362712).|||Golgi apparatus|||Membrane raft|||No visible phenotype. Mice are fertile and appear healthy when kept in a clean, microbe-free environment. Mice do not respond to bacterial smooth lipopolysaccharide (LPS). Contrary to wild-type, they do not develop toxic shock or secrete TNF in response to LPS. Surprisingly, they have fewer live bacteria in their lungs and bloodstream after inoculation with bacteria and are not killed by an inoculum that is lethal to wild-type; they are killed when the inoculum is further increased.|||Secreted|||The C-terminal leucine-rich repeat (LRR) region is required for responses to smooth LPS. http://togogenome.org/gene/10090:Luzp2 ^@ http://purl.uniprot.org/uniprot/Q8BGY3 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expression found only in the brain and spinal cord.|||Secreted http://togogenome.org/gene/10090:Or1ab2 ^@ http://purl.uniprot.org/uniprot/Q7TRY0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pgpep1 ^@ http://purl.uniprot.org/uniprot/Q9ESW8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C15 family.|||Cytoplasm|||Monomer.|||Removes 5-oxoproline from various penultimate amino acid residues except L-proline. http://togogenome.org/gene/10090:Pramel6 ^@ http://purl.uniprot.org/uniprot/Q810Y9 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Rnf135 ^@ http://purl.uniprot.org/uniprot/Q9CWS1 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E2-dependent E3 ubiquitin-protein ligase that functions as a RIGI coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response (PubMed:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIGI oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway (PubMed:21147464, PubMed:28469175, PubMed:31006531). Through a ubiquitin-independent parallel mechanism, which consists in bridging RIGI filaments forming on longer viral RNAs, further activates the RIG-I signaling pathway (PubMed:31006531). This second mechanism that synergizes with the ubiquitin-dependent one would thereby allow an RNA length-dependent regulation of the RIG-I signaling pathway (PubMed:31006531). Associated with the E2 ligase UBE2N, also constitutively synthesizes unanchored 'Lys-63'-linked polyubiquitin chains that may also activate the RIG-I signaling pathway (By similarity). It is not involved in the innate immune response against DNA viruses (PubMed:21147464).|||Homodimer. Interacts (homodimer) with RIGI (double-stranded RNA-bound oligomeric form); involved in both RIGI ubiquitination, oligomerization into filaments associated with viral RNAs and the bridging of these filaments. Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated ubiquitination of RIGI and activation of the RIG-I signaling pathway. Interacts with PCBP2.|||Mice lacking Rnf135 develop and breed normally (PubMed:21147464). They are susceptible to RNA viruses infection (PubMed:21147464).|||Stress granule|||The B30.2/SPRY domain mediates the interaction with the substrate RIGI.|||The coiled-coil domains mediate homodimerization and the bridging of viral RNA-associated RIGI filaments.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Tubb1 ^@ http://purl.uniprot.org/uniprot/A2AQ07 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with RANBP10.|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Fgr ^@ http://purl.uniprot.org/uniprot/P14234 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autophosphorylation. Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400. Activated by phorbol myristate acetate, phosphatidic acid and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Expressed in natural killer cells (at protein level).|||Interacts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G and FCGR2. Interacts (via SH2 domain) with SYK (tyrosine phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PTK2/FAK1. Interacts (via SH2 domain) with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and PTPNS1. Interacts (not phosphorylated on tyrosine residues) with CBL; FGR tyrosine phosphorylation promotes dissociation (By similarity). Interacts with CLNK (PubMed:16439675).|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||No visible phenotype. Mice lacking both Fgr and Hck are normal and fertile, but show increased susceptibility to infection with Listeria monocytogenes. In addition, their polymorphonuclear leukocytes show defects in cell spreading and adhesion.|||Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCER1G and FCGR2. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes (PubMed:11672534). Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages (PubMed:8666673, PubMed:9687507). Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation (PubMed:15561106). Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling (PubMed:21746961). Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (PubMed:16439675).|||Phosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2 engagement, cell adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-511 by SRC inhibits ulterior autophosphorylation at Tyr-400 (By similarity).|||Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation (By similarity).|||cytoskeleton|||cytosol|||ruffle membrane http://togogenome.org/gene/10090:Wdr46 ^@ http://purl.uniprot.org/uniprot/Q9Z0H1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with DDX21, NCL, NOP2 and EBNA1BP2.|||Scaffold component of the nucleolar structure. Required for localization of DDX21 and NCL to the granular compartment of the nucleolus. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Or4k1 ^@ http://purl.uniprot.org/uniprot/Q7TRM6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rps8 ^@ http://purl.uniprot.org/uniprot/P62242|||http://purl.uniprot.org/uniprot/Q497E9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS8 family.|||Component of the small ribosomal subunit (PubMed:36517592). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||Membrane|||nucleolus http://togogenome.org/gene/10090:Hivep2 ^@ http://purl.uniprot.org/uniprot/Q3UHF7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 13.5 dpc and 15.5 dpc expressed in anterior neural tube over primordial frontal cortex, spinal cord, dorsal root glanglia and developing skeletal muscle.|||Expressed in heart, lung, skeletal muscle and liver. In the brain expressed in cerebral cortex, hippocampus, corpora amygdala and cerebellar cortex.|||Interacts with TCF4.|||Nucleus|||Specifically binds to the DNA sequence 5'-GGGACTTTCC-3' which is found in the enhancer elements of numerous viral promoters such as those of SV40, CMV, or HIV1. In addition, related sequences are found in the enhancer elements of a number of cellular promoters, including those of the class I MHC, interleukin-2 receptor, somatostatin receptor II, and interferon-beta genes. It may act in T-cell activation (By similarity). http://togogenome.org/gene/10090:Gm8909 ^@ http://purl.uniprot.org/uniprot/A7VMS6|||http://purl.uniprot.org/uniprot/G3UXE9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Spag11b ^@ http://purl.uniprot.org/uniprot/Q3UW43 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antimicrobial activity against E.coli (By similarity). Plays a role in the defense response in the male reproductive tract, contributing to sperm maturation, storage and protection (By similarity).|||Secreted http://togogenome.org/gene/10090:Pramel50 ^@ http://purl.uniprot.org/uniprot/Q6P8K3 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Hgh1 ^@ http://purl.uniprot.org/uniprot/Q8C3I8 ^@ Similarity ^@ Belongs to the HGH1 family. http://togogenome.org/gene/10090:Alox12b ^@ http://purl.uniprot.org/uniprot/O70582|||http://purl.uniprot.org/uniprot/Q2KHL0 ^@ Activity Regulation|||Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the lipoxygenase family.|||Binds 1 Fe cation per subunit.|||Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:16129665). Does not convert arachidonic acid to (12R)-hydroperoxyeicosatetraenoic acid/(12R)-HPETE (PubMed:10100631, PubMed:11256953). In the skin, acts upstream of ALOXE3 on the lineolate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss (PubMed:17403930, PubMed:17429434, PubMed:21558561). May also play a role in the regulation of the expression of airway mucins (By similarity).|||Cytoplasm|||Expressed in skin epidermis and other stratified epithelia including tongue and forestomach. Low levels of expression are found in trachea, brain and lung. Not expressed in intestine, liver, kidney, adipose tissue, muscle or hematopoietic cells.|||In the embryo, expression begins at day 15.5.|||Increased by calcium.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice die within 3 to 5 hours after birth due to defective skin barrier function loosing around 30% of body weight within 3 hours. Dehydration through the skin is increased 8 folds. The outside-in barrier acquisition is also affected, the skin remaining permeable at 18.5 dpc while it is impermeable in wild-type mice. The stratum corneum is more tightly packed while other layers are unaffected. Processing of filaggrin/FG is aberrant and the skin displays structural abnormalities. The cornified envelope is more fragile and the ceramide composition of the epidermis is altered.|||Mummy, a recessive ethylnitrosurea-induced mutant has a nonsense mutation in the catalytic domain of Lox12b, resulting in truncation of the protein by 68 amino acids. The affected mice are born with red, shiny skin that desiccates and appears scaly. They probably die of dehydration like mice with targeted disruption of the gene (PubMed:17429434).|||perinuclear region http://togogenome.org/gene/10090:Or4k15b ^@ http://purl.uniprot.org/uniprot/Q05A45 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adgra3 ^@ http://purl.uniprot.org/uniprot/Q7TT36 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Expressed by spermatogonial progenitor cells located within the outer cell layer of the seminiferous tubule and by multipotent adult spermatogonial-derived stem cells.|||Interacts (via PDZ-binding motif) with DLG1.|||Membrane|||Most adhesion GPCRs proteins undergo autoproteolysis at the GPS domain. ADGRA3 is predicted non-cleavable because of the lack of a consensus catalytic triad sequence within GPS domain.|||Orphan receptor that may have a role in planar cell polarity pathway. http://togogenome.org/gene/10090:Dcaf12l2 ^@ http://purl.uniprot.org/uniprot/Q8BGW4 ^@ Similarity ^@ Belongs to the WD repeat DCAF12 family. http://togogenome.org/gene/10090:Sgcg ^@ http://purl.uniprot.org/uniprot/P82348|||http://purl.uniprot.org/uniprot/Q9EQ83 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sarcoglycan beta/delta/gamma/zeta family.|||Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.|||Interacts with the syntrophin SNTA1 and FLNC. Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans.|||Most strongly expressed in skeletal and heart muscle. Also detected in proliferating myoblasts.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Aph1b ^@ http://purl.uniprot.org/uniprot/Q8C7N7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APH-1 family.|||Membrane|||Probable component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist (By similarity). Interacts with PSEN1 and PSEN2 (By similarity).|||Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A (By similarity). http://togogenome.org/gene/10090:Maged1 ^@ http://purl.uniprot.org/uniprot/Q9QYH6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals show shortened circadian period and reduced total activity.|||Cell membrane|||Cytoplasm|||Interacts with DLX5, DLX7 and MSX2 and forms homomultimers. Interacts with UNC5A. Interacts with TRIM28 and PJA1. Interacts with NGFR/p75NTR and RORA.|||Involved in the apoptotic response after nerve growth factor (NGF) binding in neuronal cells. Inhibits cell cycle progression, and facilitates NGFR-mediated apoptosis. May act as a regulator of the function of DLX family members. May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. Plays a role in the circadian rhythm regulation. May act as RORA coregulator, modulating the expression of core clock genes such as BMAL1 and NFIL3, induced, or NR1D1, repressed.|||Nucleus|||Ubiquitously expressed in many adult tissues, except for the spleen. Expressed in osteoblastic and chondrogenic cell lines and also during embryonic development. http://togogenome.org/gene/10090:Mprip ^@ http://purl.uniprot.org/uniprot/P97434 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds RHOA, PPP1R12A/MBS and PPP1R12C/MBS85 through adjacent coiled coil domains. Interacts with MYZAP. Binds F-actin through its N-terminus.|||Expressed in Kidney, Brain, Heart and Lung.|||Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells.|||cytoskeleton http://togogenome.org/gene/10090:Or1j17 ^@ http://purl.uniprot.org/uniprot/Q8VGJ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnk2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1L0|||http://purl.uniprot.org/uniprot/A0A5F8MPC4|||http://purl.uniprot.org/uniprot/D3Z3U6|||http://purl.uniprot.org/uniprot/G3X9X7|||http://purl.uniprot.org/uniprot/O54967 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylation regulates kinase activity. Phosphorylation on Tyr-533 is required for interaction with SRC and is observed during association with clathrin-coated pits (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Cell membrane|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasmic vesicle membrane|||Down-regulated by EGF.|||Endosome|||Highly expressed at 14 dpc-16 dpc in the forebrain, in the proliferative ventricular zone of the neocortex and hippocampus, and in the cortical and hippocampal plates. Also observed in the septal area, the ganglionic eminence, and in the dorsal thalamus and hypothalamus. In the hindbrain, expressed in many nuclei in the brain stem and in the cerebellar anlage, external granule cell layer, in Purkinje cells and the deep cerebellar nuclei.|||Homodimer. Interacts with CSPG4 (activated). Interacts with MERTK (activated); stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3 domain). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (By similarity). Interacts with CDC42. Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1. Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4.|||Membrane|||Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.|||Nucleus|||Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced by EGF and is lysosome-dependent.|||The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR.|||The SAM-like domain is necessary for NEDD4-mediated ubiquitination. Promotes membrane localization and dimerization to allow for autophosphorylation.|||The UBA domain binds both poly- and mono-ubiquitin.|||Ubiquitously present in all tissues tested. Highly expressed in the adult central nervous system (CNS); hippocampus, neocortex, and cerebellum, both at dendritic spines and presynaptic axon terminals. Levels are strongly increased during enhanced neural activity.|||adherens junction|||clathrin-coated pit|||clathrin-coated vesicle|||cytosol http://togogenome.org/gene/10090:Fam50b ^@ http://purl.uniprot.org/uniprot/Q9WTJ8 ^@ Similarity|||Tissue Specificity ^@ Belongs to the FAM50 family.|||Widely expressed. Abundant in testis, where it is expressed in seminiferous tubules, not in the interstitium. At the cellular level, expressed in primary spermatocytes and round spermatids, but not detectable in spermatogonia, elongating spermatids, mature spermatozoa, Sertoli cells or Leydig cells. http://togogenome.org/gene/10090:Ankrd44 ^@ http://purl.uniprot.org/uniprot/B2RXR6 ^@ Function|||Subunit ^@ Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP6R1 (By similarity).|||Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates. http://togogenome.org/gene/10090:Zfp330 ^@ http://purl.uniprot.org/uniprot/Q922H9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the NOA36 family.|||Nucleus|||centromere|||nucleolus http://togogenome.org/gene/10090:Zfp551 ^@ http://purl.uniprot.org/uniprot/B2RUI1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Or5p72 ^@ http://purl.uniprot.org/uniprot/Q8VG08 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Slc2a10 ^@ http://purl.uniprot.org/uniprot/Q8VHD6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Endomembrane system|||Facilitative glucose transporter required for the development of the cardiovascular system.|||perinuclear region http://togogenome.org/gene/10090:Gpr137 ^@ http://purl.uniprot.org/uniprot/E9Q9I0|||http://purl.uniprot.org/uniprot/Q3TD99|||http://purl.uniprot.org/uniprot/Q3UPL3|||http://purl.uniprot.org/uniprot/Q3UQ21|||http://purl.uniprot.org/uniprot/Q80ZU9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GPR137 family.|||Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes. May play a role in autophagy.|||Lysosome membrane|||May activate Wnt/beta-catenin signaling to modulate epithelial cell function.|||Membrane http://togogenome.org/gene/10090:Spaca9 ^@ http://purl.uniprot.org/uniprot/Q7TPM5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Deficient mice are viable, fertile, and have no clear phenotypic differences from wild-type mice.|||Expressed in sperm (at protein level) (Ref.4). Expressed from almost all the cell types of testis, with abundant expression in round and elongated spermatids (at protein level) (PubMed:24256100). Predominantly expressed in tissues containing motile cilia (PubMed:27914912).|||Expressed in the developing fetal lung epithelium (at protein level).|||Expression is activated by FOXJ1 and NOTO.|||Interacts with CABP1 and CALR (PubMed:24256100). Interacts with INCA1 (By similarity). Interacts with microtubules (By similarity).|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated spermatozoa. May stabilize the protofilaments to which they are bound.|||Nucleus|||acrosome|||cilium axoneme|||cilium basal body|||flagellum http://togogenome.org/gene/10090:Srp14 ^@ http://purl.uniprot.org/uniprot/P16254 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SRP14 family.|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (By similarity). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP (By similarity). The complex of SRP9 and SRP14 is required for SRP RNA binding (By similarity).|||Cytoplasm|||Heterodimer with SRP9; binds RNA as heterodimer (By similarity). Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9 (PubMed:9233785). http://togogenome.org/gene/10090:Znhit1 ^@ http://purl.uniprot.org/uniprot/Q8R331 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZNHIT1 family.|||Component of the chromatin-remodeling SRCAP complex composed of at least SRCAP, DMAP1, RUVBL1, RUVBL2, ACTL6A, YEATS4, ACTR6 and ZNHIT1 (By similarity). Interacts with MAPK11 and MAPK14 (By similarity). Interacts with NR1D1 and NR2D2 (By similarity). Interacts (via HIT-type zinc finger) with the RUVBL1/RUVBL2 complex in the presence of ADP (By similarity). Interacts with histone deacetylase HDAC1 (PubMed:19501046). Interacts with histone H2AZ1; the interaction results in recruitment of H2AZ1 to the MYOG promoter region (By similarity). Interacts with PCID2; the interaction results in inhibition of SRCAP complex activity, preventing the deposition of histone variant H2AZ1 to lymphoid fate regulator genes and restricting lymphoid lineage commitment (PubMed:29138493).|||Conditional knockout in hematopoietic stem cells abrogates deposition of histone variant H2az1/H2A.Z to lymphoid fate regulator genes and causes reduced bone marrow cellularity and a decreased number of common lymphoid progenitors but an increased number of common myeloid progenitors compared with wild-type mice (PubMed:29138493). Conditional knockout in intestinal epithelium results in intestinal epithelium dysfunction after birth with dramatic body weight decrease leading to the death of 30% of mice after the first postnatal week while survivors show obvious growth retardation at P30 (PubMed:30842416). Intestinal villi and inter-villi structures are normal at 18.5 dpc but enlarged crypts and defective villi are observed during the postnatal crypt morphogenesis stage with depletion of Lgr5+ intestinal stem cells (PubMed:30842416). Conditional knockout in hematopoietic stem cells (HSCs) results in dramatic HSC expansion (PubMed:32694618). Conditional knockout in male germ cells blocks meiotic initiation, resulting in defective spermatogenesis and male infertility (PubMed:35413238). Conditional knockout in postnatal cardiomyocytes results in arrhythmia, idiopathic vacuolar cardiomyopathy, rapid heart failure and premature sudden death with massively elevated levels of Casq1 and reduced levels of Atp2a2/Serca2 (PubMed:35167494). Conditional knockout in embryonic cardiomyocytes results in reduced protein levels of Vps72/Yl1 and histone H2az1 with impairment of heart development by 13.5 dpc and heart failure by 18.5 dpc (PubMed:33913477). Mutants start to die from 17.5 dpc with half dying before birth and the remainder surviving after birth for less than half a day (PubMed:33913477). Mutants show myocardial mitochondrial swelling, severe damage to the cristae and impaired integrity of the respiratory complex (PubMed:33913477). Conditional knockout in the lens results in severe cataracts, microphthalmia, lens fibrosis, abnormal lens fiber cell differentiation with decreased cell proliferation and increased cell apoptosis of the lens epithelia, increased chromatin accessibility of the Cdkn1a/p21Cip1 and Cdkn1c/p57Kip2 promoters and increased Cdkn1a and Cdkn1c levels (PubMed:35472217).|||Expression increases during muscle differentiation (at protein level) (PubMed:20473270). In the lens, expressed at high levels throughout embryonic and early postnatal stages and then gradually diminishes to adulthood (at protein level) (PubMed:35472217). In the developing embryonic heart, expression is significantly increased at 11.5 dpc and 12.5 dpc (PubMed:33913477).|||Higher expression in testis than in other tissues (at protein level) (PubMed:35413238). Expressed in the lens (at protein level) (PubMed:35472217). In the intestinal epithelium, expression is enriched at the bottom of crypts (PubMed:30842416). In hematopoietic cells, enriched in hematopoietic stem cells and progenitors with significantly reduced expression in differentiated cells such as granulocytes, monocytes, T cells and B cells (PubMed:32694618).|||Nucleus|||Phosphorylated on Thr by MAPK11 or MAPK14 (PubMed:20473270). Phosphorylation is required for MYOG induction, for deposition of histone H2AZ1 at the MYOG promoter and for SRCAP complex integrity (By similarity).|||Plays a role in chromatin remodeling by promoting the incorporation of histone variant H2AZ1/H2A.Z into the genome to regulate gene expression (PubMed:29138493, PubMed:30842416, PubMed:32694618, PubMed:33913477, PubMed:35413238, PubMed:35167494). Promotes SRCAP complex-mediated deposition of histone variant H2AZ1 to lymphoid fate regulator genes, enhancing lymphoid lineage commitment (PubMed:29138493). Recruited to the promoter of the transcriptional activator MYOG at the early stages of muscle differentiation where it mediates binding of histone variant H2AZ1 to chromatin and induces muscle-specific gene expression (By similarity). Maintains hematopoietic stem cell (HSC) quiescence by determining the chromatin accessibility at distal enhancers of HSC quiescence genes such as PTEN, FSTL1 and KLF4, enhancing deposition of H2AZ1 to promote their sustained transcription and restricting PI3K-AKT signaling inhibition (PubMed:32694618). Plays a role in intestinal stem cell maintenance by promoting H2AZ1 deposition at the transcription start sites of genes involved in intestinal stem cell fate determination including LGR5, TGFB1 and TGFBR2, thereby contributing to gene transcription (PubMed:30842416). Promotes phosphorylation of the H2AZ1 chaperone VPS72/YL1 which enhances the interaction between HZAZ1 and VPS72 (PubMed:30842416). Regulates the entry of male germ cells into meiosis by controlling histone H2AZ1 deposition which facilitates the expression of meiotic genes such as MEIOSIN, leading to the initiation of meiosis (PubMed:35413238). Required for postnatal heart function through its role in maintenance of cardiac Ca(2+) homeostasis by modulating the expression of Ca(2+)-regulating proteins CASQ1 and ATP2A2/SERCA2A via deposition of histone H2AZ1 at their promoters (PubMed:35167494). During embryonic heart development, required for mitochondrial maturation and oxidative metabolism by functioning through H2AZ1 deposition to activate transcription of metabolic genes and is also required to maintain the stability of the respiratory complex (PubMed:33913477). In neural cells, increases deposition of the H2AZ1 histone variant and promotes neurite growth (By similarity). Plays a role in TP53/p53-mediated apoptosis induction by stimulating the transcriptional activation of several proapoptotic p53 target genes such as PMAIP1/NOXA and BBC3/PUMA (By similarity). Mediates cell cycle arrest induced in response to gamma-irradiation by enhancing recruitment of TP53/p53 to the promoter of the cell cycle inhibitor CDKN1A, leading to its transcriptional activation (By similarity). Recruited to the promoter of cyclin-dependent kinase CDK6 and inhibits its transcription, possibly by decreasing the acetylation level of histone H4, leading to cell cycle arrest at the G1 phase (PubMed:19501046). Plays a role in lens fiber cell differentiation by regulating the expression of cell cycle regulator CDKN1A/p21Cip1 (PubMed:35472217). Binds to transcriptional repressor NR1D2 and relieves it of its inhibitory effect on the transcription of apolipoprotein APOC3 without affecting its DNA-binding activity (By similarity). http://togogenome.org/gene/10090:Akp3 ^@ http://purl.uniprot.org/uniprot/F8VQM0|||http://purl.uniprot.org/uniprot/Q1LZM2 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alkaline phosphatase family.|||Binds 1 Mg(2+) ion.|||Binds 2 Zn(2+) ions.|||Cell membrane|||Homodimer.|||Membrane http://togogenome.org/gene/10090:Rnf133 ^@ http://purl.uniprot.org/uniprot/Q14B02 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Auto-ubiquitinated.|||Endoplasmic reticulum membrane|||Expression begins in the testis at day 21 and increases dramatically from day 28 and thereafter.|||Has E3 ubiquitin-protein ligase activity.|||Testis-specific. http://togogenome.org/gene/10090:Or13a26 ^@ http://purl.uniprot.org/uniprot/Q8VGM0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccnd3 ^@ http://purl.uniprot.org/uniprot/P30282|||http://purl.uniprot.org/uniprot/Q3TSW4|||http://purl.uniprot.org/uniprot/Q3TWY0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin D subfamily.|||Cytoplasm|||Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex. Interacts with ATF5. Interacts with EIF3K. Component of the ternary complex cyclin D/CDK4/CDKN1B required for nuclear translocation and modulation of CDK4-mediated kinase activity. Can form similar complexes with either CDKN1A or CDKN2A.|||Nucleus|||Phosphorylation at Thr-283 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.|||Regulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Shows transcriptional coactivator activity with ATF5 independently of CDK4.|||Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-283 phosphorylation (PubMed:33854232, PubMed:33854235). The DCX(AMBRA1) complex represents the major regulator of CCND3 stability during the G1/S transition (PubMed:33854232, PubMed:33854235). Polyubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Gtf3a ^@ http://purl.uniprot.org/uniprot/Q8VHT7 ^@ Caution|||Function|||Subcellular Location Annotation ^@ Involved in ribosomal large subunit biogenesis. Binds the approximately 50 base pairs internal control region (ICR) of 5S ribosomal RNA genes. It is required for their RNA polymerase III-dependent transcription and may also maintain the transcription of other genes (By similarity). Also binds the transcribed 5S RNA's (By similarity).|||It is uncertain whether Met-1 is the initiator. Based on the lack of an in-frame AUG codon, mammalian TFIIIA may be translated from this non-AUG initiation site, which has a good Kozak context and which is well conserved among mammals.|||Nucleus http://togogenome.org/gene/10090:Mrln ^@ http://purl.uniprot.org/uniprot/Q9CV60 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During embryogenesis, expressed in the myotomal compartment of the somites and the anlagen of skeletal muscle. During fetal and adult stages, strongly expressed in all skeletal muscles. Not detectable in cardiac or smooth muscles.|||Expression is regulated by MYEF2 and MYOD1.|||Inhibits the activity of ATP2A1/SERCA1 ATPase in sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+), thereby acting as a key regulator of skeletal muscle activity. Its high expression in adult skeletal muscle, suggests that it constitutes the predominant regulator of ATP2A1/SERCA1 in adult skeletal muscle.|||Interacts with ATP2A1/SERCA1.|||Mice were born at expected Mendelian ratios and did not show no obvious morphological abnormalities or differences in body or muscle weights. They however show enhanced Ca(2+) handling in skeletal muscle and improved exercise performance.|||Sarcoplasmic reticulum membrane|||Specifically expressed in all skeletal muscles. Not expressed in cardiac or smooth muscles. http://togogenome.org/gene/10090:Ccdc115 ^@ http://purl.uniprot.org/uniprot/Q8VE99 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump.|||Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. In aerobic conditions, required for intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. Necessary for endolysosomal acidification and lysosomal degradation (By similarity). May be involved in Golgi homeostasis (By similarity).|||COPI-coated vesicle|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Endosome|||Lysosome|||Modestly up-regulated by FGF2.|||Predominantly expressed in the heart, liver, kidney and testis and at lower levels in the brain and lung. Undetectable in the spleen and muscles.|||Strongly expressed at 13.5 dpc in a ventro-lateral area of striatum and piriform cortex. At 14.5 dpc, some of the positive cells shift toward the cortical plate. At this stage, strongly observed at the superficial layer of dorsal cortex, whereas that of ventral cortex decreases in its intensity. Expression extended further dorsally at 16.5 dpc. In the dorsal cortex, expressed in the ventricular zone at 13.5 dpc. At later stages, expression shifts to the cortical plate. At 15.5 dpc, localizes to both ventricular zone and cortical plate. At 16.5 dpc, almost all expression is in the deeper cortical plate, although some expressing cells are still detectable in the ventricular zone. In the lateral cortex, weak expression in the lateral ganglionic eminence at 13.5 dpc. At 15.5 dpc, strongly detected in the progenitor zones of the lateral ganglionic eminence and medial ganglionic eminence, as well as in tangentially migrating cells in the superficial area of lateral cortex. In the striatum and ventro-lateral cortex, expressed at both 13.5 dpc and 15.5 dpc. http://togogenome.org/gene/10090:Cntf ^@ http://purl.uniprot.org/uniprot/P51642|||http://purl.uniprot.org/uniprot/Q544D1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CNTF family.|||CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.|||Cytoplasm|||Nervous system. http://togogenome.org/gene/10090:B3glct ^@ http://purl.uniprot.org/uniprot/Q8BHT6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Endoplasmic reticulum membrane|||O-glucosyltransferase that transfers glucose toward fucose with a beta-1,3 linkage. Specifically glucosylates O-linked fucosylglycan on TSP type-1 domains of proteins, thereby contributing to elongation of O-fucosylglycan (By similarity). http://togogenome.org/gene/10090:Nat8 ^@ http://purl.uniprot.org/uniprot/Q9JIY7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylates the free alpha-amino group of cysteine S-conjugates to form mercapturic acids. This is the final step in a major route for detoxification of a wide variety of reactive electrophiles which starts with their incorporation into glutathione S-conjugates. The glutathione S-conjugates are then further processed into cysteine S-conjugates and finally mercapturic acids which are water soluble and can be readily excreted in urine or bile. Alternatively, may have a lysine N-acetyltransferase activity catalyzing peptidyl-lysine N6-acetylation of various proteins. Thereby, may regulate apoptosis through the acetylation and the regulation of the expression of PROM1. May also regulate amyloid beta-peptide secretion through acetylation of BACE1 and the regulation of its expression in neurons (By similarity).|||Belongs to the camello family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Expressed in brain (at protein level).|||Interacts with PROM1. Interacts with BACE1 (By similarity). http://togogenome.org/gene/10090:Or4a73 ^@ http://purl.uniprot.org/uniprot/Q7TQZ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zscan10 ^@ http://purl.uniprot.org/uniprot/Q3URR7 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Embryonic stem (ES) cell-specific transcription factor required to maintain ES cell pluripotency. Can both activate and /or repress expression of target genes, depending on the context. Specifically binds the 5'-[GA]CGCNNGCG[CT]-3' DNA consensus sequence. Regulates expression of POU5F1/OCT4, ZSCAN4 and ALYREF/THOC4.|||Embryonic stem (ES) cell-specific. Not expressed in adult, except in testis.|||Expressed throughout embryogenesis.|||Interacts with POU5F1/OCT4 and SOX2.|||Methylated at Gln-485 by N6AMT1.|||Nucleus|||Transcriptionally regulated by POU5F1/OCT4 and SOX2. http://togogenome.org/gene/10090:Ppp1r16b ^@ http://purl.uniprot.org/uniprot/Q544H9|||http://purl.uniprot.org/uniprot/Q8VHQ3 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cell projection|||Inhibited by TGF-beta1 (Probable). Down-regulated by LPS (PubMed:21907835).|||Interacts with PPP1CA, PPP1CB and MSN. Interacts (via its fourth ankyrin repeat) with the mature dimeric form of RPSA/LAMR1 (By similarity). Interacts with EEF1A1 (By similarity). Interacts with PTEN (By similarity). Interacts with ECE1 (By similarity).|||Membrane|||Nucleus|||Phosphorylated by PKA and, after PKA priming, by GSK3B. Phosphorylation by GSK3B reduces its association with PP1C and enhances PP1C activity. Dephosphorylation by its associated PP1C results in enhanced association with PP1C, but reduced PP1C activity (By similarity).|||Regulator of protein phosphatase 1 (PP1) that acts as a positive regulator of pulmonary endothelial cell (EC) barrier function. Protects the endothelial barrier from lipopolysaccharide (LPS)-induced vascular leakage (PubMed:21907835). Involved in the regulation of the PI3K/AKT signaling pathway (By similarity). Involved in the regulation of angiogenesis and endothelial cell proliferation through the control of ECE1 dephosphorylation, trafficking and activity (By similarity). Involved in the regulation of endothelial cell filopodia extension (By similarity). May be a downstream target for TGF-beta1 signaling cascade in endothelial cells (By similarity). Involved in PKA-mediated moesin dephosphorylation which is important in EC barrier protection against thrombin stimulation. Promotes the interaction of PPP1CA with RPSA/LAMR1 and in turn facilitates the dephosphorylation of RPSA/LAMR1 (By similarity). Involved in the dephosphorylation of EEF1A1 (By similarity). http://togogenome.org/gene/10090:Serinc4 ^@ http://purl.uniprot.org/uniprot/Q5XK03 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TDE1 family.|||Incorporates a polar amino acid serine into membranes and facilitates the synthesis of two serine-derived lipids, phosphatidylserine and sphingolipids.|||Membrane http://togogenome.org/gene/10090:Cry1 ^@ http://purl.uniprot.org/uniprot/P97784 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA photolyase class-1 family.|||Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per subunit.|||Binds 1 FAD per subunit. Only a minority of the protein molecules contain bound FAD. Contrary to the situation in photolyases, the FAD is bound in a shallow, surface-exposed pocket.|||Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins (PubMed:11779462). Interacts directly with TIMELESS (PubMed:10428031, PubMed:24489120, PubMed:23418588). Interacts directly with PER1 and PER2; interaction with PER2 inhibits its ubiquitination and vice versa (PubMed:10428031, PubMed:11889036, PubMed:11875063, PubMed:14701732, PubMed:16478995, PubMed:23746849, PubMed:23418588, PubMed:21613214, PubMed:20159955). Interacts with PER3 (PubMed:10428031, PubMed:14701732). Interacts with FBXL21 (PubMed:18953409, PubMed:23452855, PubMed:23452856). Interacts with FBXL3 (PubMed:17462724, PubMed:23746849, PubMed:23452855, PubMed:23452856, PubMed:30500822). Interacts with PPP5C (via TPR repeats) (By similarity). Interacts with CLOCK-BMAL1 independently of PER2 and DNA (PubMed:21613214). Interacts with HDAC1, HDAC2 and SIN3B (PubMed:15226430). Interacts with nuclear receptors AR, NR1D1, NR3C1/GR, RORA and RORC; the interaction with at least NR3C1/GR is ligand dependent (PubMed:22170608, PubMed:28751364). Interacts with PRKDC (PubMed:24158435). Interacts with the G protein subunit alpha GNAS; the interaction may block GPCR-mediated regulation of cAMP concentrations (By similarity). Interacts with PRMT5 (PubMed:23133559). Interacts with EZH2 (PubMed:16717091). Interacts with MYBBP1A, DOCK7, HNRNPU, RPL7A, RPL8 and RPS3 (PubMed:19129230). Interacts with MAP1LC3B (PubMed:29937374). Interacts with CLOCK (PubMed:16717091, PubMed:19917250). Interacts with BMAL1 (PubMed:26776516, PubMed:16717091, PubMed:19917250, PubMed:23746849). Interacts weakly with HDAC3; this interaction is enhanced in the presence of FBXL3 (PubMed:26776516). Interacts with TRIM28, KCTD5 and DDB1 (PubMed:27123980). Interacts with DTL (By similarity). Interacts with DDB1-CUL4A complex (PubMed:26431207). Interacts with FOXO1 (PubMed:28790135). Interacts with PSMD2 in a KDM8-dependent manner (PubMed:30500822). Interacts with KDM8 in a FBXL3-dependent manner (PubMed:30500822). Interacts with PPARA (PubMed:28683290). Interacts with PPARG in a ligand-dependent manner (PubMed:28683290). Interacts with PPARD (via domain NR LBD) in a ligand-dependent manner (PubMed:28683290, PubMed:28751364). Interacts with NR1I2 (via domain NR LBD) in a ligand-dependent manner (PubMed:28751364). Interacts with NR1I3, VDR and HNF4A (PubMed:28751364).|||Cytoplasm|||Expressed in cones, amacrine cells, and retinal ganglion cells of the retina (at protein level) (PubMed:29561690). Expressed in all tissues examined including heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis. Higher levels in brain, liver and testis. In the retina, highly expressed in the ganglion cell layer (GCL) and in the inner nuclear layer (INL). Evenly distributed in central and peripheral retina. In the brain, highly expressed in the suprachiasmatic nucleus (SCN). High levels in cerebral cortical layers particularly in the pyramidial cell layer of the hippocampus, the granular cell layer of the dentate gyrus (DG) and the pyramidal cell layer of the piriform cortex (PFC).|||KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1 resulting in lengthening of the circadian periods. KL001-mediated CRY1 stabilization can inhibit glucagon-induced gluconeogenesis in primary hepatocytes.|||Mice show an advanced phase shift (around 4 hours) in the expression of DBP, NR1D1 and PER1 genes in the liver. Double knockouts of CRY1 and CRY2 show slightly decrease body weight and lose the cycling rhythmicity of feeding behavior, energy expenditure and glucocorticoids expression. Glucose homeostasis is severely disrupted and animals exhibit elevated blood glucose in response to acute feeding after an overnight fast as well as severely impaired glucose clearance in a glucose tolerance test. When challenged with high-fat diet, animals rapidly gain weight and surpass that of wild-type mice, despite displaying hypophagia. They exhibit hyperinsulinemia and selective insulin resistance in the liver and muscle but show high insulin sensitivity in adipose tissue and consequent increased lipid uptake. Mice display enlarged gonadal, subcutaneous and perirenal fat deposits with adipocyte hypertrophy and increased lipied accumulation in liver. Mice show loss of circadian rhythms in photopic ERG b-wave amplitudes, visual contrast sensitivity and pupillary light responses, with reduced robustness and stability of bioluminescent rhythms (PubMed:29561690). Both single CRY1 knockout and double CRY1 and CRY2 knockout mice show increased exercise performance and increased mitochondrial reserve capacity in primary myotubes (PubMed:28683290).|||Nucleus|||Oscillates diurnally, rhythmic expression in the early night is critical for clock function (at protein level). In SCN, exhibits circadian rhythm expression with highest levels during the light phase at CT10. No detectable expression after 8 hours in the dark. Circadian oscillations also observed in liver, skeletal muscle and cerebellum, but not in testis.|||Phosphorylation on Ser-247 by MAPK is important for the inhibition of CLOCK-BMAL1-mediated transcriptional activity. Phosphorylation by CSNK1E requires interaction with PER1 or PER2. Phosphorylation at Ser-71 and Ser-280 by AMPK decreases protein stability. Phosphorylation at Ser-588 exhibits a robust circadian rhythm with a peak at CT8, increases protein stability, prevents SCF(FBXL3)-mediated degradation and is antagonized by interaction with PRKDC.|||The LIR motifs (LC3-interacting region) 3 and 5 are required for its interaction with MAP1LC3B and for its autophagy-mediated degradation.|||Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. More potent transcriptional repressor in cerebellum and liver than CRY2, though more effective in lengthening the period of the SCN oscillator. On its side, CRY2 seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY2, is dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. Interacts with CLOCK-BMAL1 independently of PER proteins and is found at CLOCK-BMAL1-bound sites, suggesting that CRY may act as a molecular gatekeeper to maintain CLOCK-BMAL1 in a poised and repressed state until the proper time for transcriptional activation. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1, ATF4, MTA1, KLF10 and NAMPT. May repress circadian target genes expression in collaboration with HDAC1 and HDAC2 through histone deacetylation. Mediates the clock-control activation of ATR and modulates ATR-mediated DNA damage checkpoint. In liver, mediates circadian regulation of cAMP signaling and gluconeogenesis by binding to membrane-coupled G proteins and blocking glucagon-mediated increases in intracellular cAMP concentrations and CREB1 phosphorylation. Inhibits hepatic gluconeogenesis by decreasing nuclear FOXO1 levels that down-regulates gluconeogenic gene expression. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity (PubMed:28683290). Plays an essential role in the generation of circadian rhythms in the retina (PubMed:29561690). Represses the transcriptional activity of NR1I2 (PubMed:28751364).|||Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complexes, regulating the balance between degradation and stabilization. The SCF(FBXL3) complex is mainly nuclear and mediates ubiquitination and subsequent degradation of CRY1. In contrast, cytoplasmic SCF(FBXL21) complex-mediated ubiquitination leads to stabilize CRY1 and counteract the activity of the SCF(FBXL3) complex. The SCF(FBXL3) and SCF(FBXL21) complexes probably mediate ubiquitination at different Lys residues. Ubiquitination at Lys-11 and Lys-107 are specifically ubiquitinated by the SCF(FBXL21) complex but not by the SCF(FBXL3) complex. Ubiquitination may be inhibited by PER2. Deubiquitinated by USP7 (PubMed:27123980).|||Undergoes autophagy-mediated degradation in the liver in a time-dependent manner. Autophagic degradation of CRY1 (an inhibitor of gluconeogenesis) occurs during periods of reduced feeding allowing induction of gluconeogenesis and maintenance of blood glucose levels. http://togogenome.org/gene/10090:Tmprss11d ^@ http://purl.uniprot.org/uniprot/Q8VHK8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Highly expressed in the esophagus, tongue, and trachea, low expression was seen in heart, lung, and adrenal gland. Isoform 2 is also highly expressed in the adrenal gland.|||May play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. Preferentially cleaves the C-terminal side of arginine residues at the P1 position of certain peptides (By similarity). Plays a role in the proteolytic processing of ACE2. Isoform 2 may play a key role in regulating adrenal proliferation by specifically cleaving N-POMC.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Or2z8 ^@ http://purl.uniprot.org/uniprot/Q7TRY2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gkn1 ^@ http://purl.uniprot.org/uniprot/Q9CR36 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the gastrokine family.|||Cytoplasmic granule|||Expressed in the stomach (PubMed:15221938). Highly expressed specifically in surface cells of the antrum mucosa from where it is secreted.|||Golgi apparatus|||Has mitogenic activity and may be involved in maintaining the integrity of the gastric mucosal epithelium.|||Secreted http://togogenome.org/gene/10090:Btnl6 ^@ http://purl.uniprot.org/uniprot/A2CG22 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Membrane http://togogenome.org/gene/10090:Dnajc9 ^@ http://purl.uniprot.org/uniprot/Q91WN1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a dual histone chaperone and heat shock co-chaperone (By similarity). As a histone chaperone, forms a co-chaperone complex with MCM2 and histone H3-H4 heterodimers; and may thereby assist MCM2 in histone H3-H4 heterodimer recognition and facilitate the assembly of histones into nucleosomes (By similarity). May also act as a histone co-chaperone together with TONSL (By similarity). May recruit histone chaperones ASF1A, NASP and SPT2 to histone H3-H4 heterodimers (By similarity). Also plays a role as co-chaperone of the HSP70 family of molecular chaperone proteins, such as HSPA1A, HSPA1B and HSPA8 (By similarity). As a co-chaperone, may play a role in the recruitment of HSP70-type molecular chaperone machinery to histone H3-H4 substrates, thereby maintaining the histone structural integrity (By similarity). Exhibits activity to assemble histones onto DNA in vitro (By similarity).|||Cell membrane|||Cytoplasm|||Forms a co-chaperone complex with MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts (via C-terminus) with MCM2 (via N-terminus); the interaction is histone-dependent (By similarity). Within the complex, interacts (via C-terminus) with histone H3.3-H4 heterodimers; the interaction is direct (By similarity). Interacts with histones H4, H3.3, H3.2 and H3.1, but not with CENPA or the testis-specific histone H3.1t (By similarity). Interacts (via J domain) with HSPA1A, HSPA1B and HSPA8 (By similarity). May interact with TONSL; the interaction seems to be histone-dependent (By similarity). May interact with HSPA8 and BAG2; the interactions seem to be histone-dependent (By similarity).|||Nucleus|||The functional J domain is required for the release from histone-dependent chromatin-binding. http://togogenome.org/gene/10090:Or5ak24 ^@ http://purl.uniprot.org/uniprot/Q8VF73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrrc56 ^@ http://purl.uniprot.org/uniprot/Q8K375 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LRRC56 family.|||Interacts with IFT88.|||Required for the assembly of dynein arms.|||cilium http://togogenome.org/gene/10090:Cox20 ^@ http://purl.uniprot.org/uniprot/Q9D7J4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COX20 family.|||Essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Acts as a chaperone in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation, stabilizing the newly synthesized protein and presenting it to metallochaperones SCO1/2 which in turn facilitates the incorporation of the mature MT-CO2/COX2 into the assembling CIV holoenzyme.|||Found in a complex with TMEM177, COA6, MT-CO2/COX2, COX18, SCO1 and SCO2. Interacts with SCO1, SCO2 and COA6 in a MT-CO2/COX2- and COX18-dependent manner. Interacts with COX18 in a MT-CO2/COX2-dependent manner. Interacts with MT-CO2/COX2 and TMEM177.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Polr1has ^@ http://purl.uniprot.org/uniprot/Q8R0E5 ^@ Function|||Tissue Specificity ^@ May be involved in male sterility.|||Specifically expressed in testis. http://togogenome.org/gene/10090:Echdc2 ^@ http://purl.uniprot.org/uniprot/Q3TLP5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||Mitochondrion http://togogenome.org/gene/10090:Prkra ^@ http://purl.uniprot.org/uniprot/Q9WTX2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRKRA family.|||Cytoplasm|||Expressed in brain, heart, kidney, liver, lung, muscle, spleen and testis.|||Homodimer. Interacts with DICER1, AGO2 and TARBP2. Also able to interact with dsRNA (By similarity). Interacts with EIF2AK2/PKR through its DRBM domains. Interacts with DUS2L (via DRBM domain) (By similarity). Interacts with UBC9. Forms a complex with UBC9 and p53/TP53.|||Phosphorylated at Ser-246 in unstressed cells and at Ser-287 in stressed cells. Phosphorylation at Ser-246 appears to be a prerequisite for subsequent phosphorylation at Ser-287. Phosphorylation at Ser-246 and Ser-287 are necessary for activation of EIF2AK2/PKR under conditions of stress (By similarity).|||Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1 (By similarity). Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner.|||Self-association may occur via interactions between DRBM domains as follows: DRBM 1/DRBM 1, DRBM 1/DRBM 2, DRBM 2/DRBM 2 or DRBM 3/DRBM3.|||perinuclear region http://togogenome.org/gene/10090:Chad ^@ http://purl.uniprot.org/uniprot/O55226 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily.|||Cartilage.|||Mostly monomeric. Interacts with collagen type II (By similarity).|||Promotes attachment of chondrocytes, fibroblasts, and osteoblasts. This binding is mediated (at least for chondrocytes and fibroblasts) by the integrin alpha(2)beta(1). May play an important role in the regulation of chondrocyte growth and proliferation (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Tnfrsf1a ^@ http://purl.uniprot.org/uniprot/P25118|||http://purl.uniprot.org/uniprot/Q3U479 ^@ Caution|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Glycosylated at Arg-376 by S.typhimurium protein Ssek3: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions.|||Binding of TNF to the extracellular domain leads to homotrimerization. The aggregated death domains provide a novel molecular interface that interacts specifically with the death domain of TRADD. Various TRADD-interacting proteins such as TRAFS, RIPK1 and possibly FADD, are recruited to the complex by their association with TRADD. This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4, BABAM2, FEM1B, GRB2, SQSTM1 and TRPC4AP. Interacts with DAB2IP (By similarity). Interacts directly with NOL3 (via CARD domain); inhibits TNF-signaling pathway (PubMed:24440909). Interacts with SH3RF2, TRADD and RIPK1. SH3RF2 facilitates the recruitment of RIPK1 and TRADD to TNFRSF1A in a TNF-alpha-dependent process (By similarity). Interacts with PGLYRP1; this interaction is important for cell death induction (By similarity). Interacts (via death domain) with MADD (via death domain) (By similarity).|||Both the cytoplasmic membrane-proximal region and the C-terminal region containing the death domain are involved in the interaction with TRPC4AP.|||Cell membrane|||Golgi apparatus membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (By similarity). http://togogenome.org/gene/10090:Mybphl ^@ http://purl.uniprot.org/uniprot/Q5FW53 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. MyBP family.|||Expressed in the atria as well as in discrete puncta throughout the right ventricular wall and septum.|||Knockout mouse hearts exhibit a 36% reduction in fractional shortening and an increased diastolic ventricular chamber size (PubMed:28778945). Mutants show cardiac conduction system abnormalities with aberrant atrioventricular conduction and an increased rate of arrhythmia (PubMed:28778945).|||Myosin-binding protein which plays a role in cardiac function (PubMed:28778945). Seems to regulate conduction in the atria and ventricular conduction systems (PubMed:28778945).|||sarcomere http://togogenome.org/gene/10090:Enam ^@ http://purl.uniprot.org/uniprot/O55196 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in developing teeth.|||Involved in the mineralization and structural organization of enamel. Involved in the extension of enamel during the secretory stage of dental enamel formation.|||Phosphorylated by FAM20C in vitro.|||extracellular matrix http://togogenome.org/gene/10090:4921509C19Rik ^@ http://purl.uniprot.org/uniprot/Q8C0X8 ^@ Function|||Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Smok subfamily.|||May play a role in sperm motility, especially in the regulation of flagellar function. http://togogenome.org/gene/10090:Acot4 ^@ http://purl.uniprot.org/uniprot/Q14DI6|||http://purl.uniprot.org/uniprot/Q8BWN8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the C/M/P thioester hydrolase family.|||Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16141203, PubMed:16940157). In contrast to its human ortholog, functions essentially as a succinyl-CoA thioesterase with no activity with medium to long chain saturated acyl-CoAs and with a low activity toward glutaryl-CoA (PubMed:16141203, PubMed:16940157).|||In the liver, by peroxisome proliferator (Clofibrate) treatment, via the peroxisome proliferator-activated receptors (PPARs) or fasting for 24 hours.|||Mainly expressed in liver and kidney. Weakly expressed in other tissues including intestine, adrenal gland and adipose tissues.|||Peroxisome http://togogenome.org/gene/10090:Zc3h11a ^@ http://purl.uniprot.org/uniprot/Q6NZF1 ^@ Function|||Sequence Caution|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Interacts with THOC2, DDX39 and POLDIP3; the interactions are ATP-dependent and indicative for an association with the TREX complex.|||Involved in nuclear mRNA export; probably mediated by association with the TREX complex. http://togogenome.org/gene/10090:Mcm2 ^@ http://purl.uniprot.org/uniprot/P97310 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by MCM3AP.|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division (PubMed:10567526). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (By similarity).|||Belongs to the MCM family.|||Chromosome|||Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (By similarity). Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (By similarity). Interacts with DBF4 (PubMed:10517317). Interacts with KAT7 (PubMed:11278932). May interact with MCM10 (By similarity). Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR (By similarity). Forms a co-chaperone complex with DNAJC9 and histone H3.3-H4 heterodimers (By similarity). Within the complex, interacts (via N-terminus) with DNAJC9 (via C-terminus); the interaction is histone-dependent (By similarity).|||Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.|||Nucleus|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.|||Phosphorylated on Ser-108 by ATR in proliferating cells. Ser-108 proliferation is increased by genotoxic agents. Ser-40 is mediated by the CDC7-DBF4 and CDC7-DBF4B complexes, while Ser-53 phosphorylation is only mediated by the CDC7-DBF4 complex. Phosphorylation by the CDC7-DBF4 complex during G1/S phase is required for the initiation of DNA replication (By similarity). http://togogenome.org/gene/10090:Mgme1 ^@ http://purl.uniprot.org/uniprot/Q9CXC3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MGME1 family.|||Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endoduclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair (By similarity). Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells.|||Mitochondrion http://togogenome.org/gene/10090:Tmem241 ^@ http://purl.uniprot.org/uniprot/Q3UME2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM241 family.|||Membrane http://togogenome.org/gene/10090:Or6c69b ^@ http://purl.uniprot.org/uniprot/Q8VFH9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krtcap3 ^@ http://purl.uniprot.org/uniprot/Q8K177 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM54 family.|||Membrane http://togogenome.org/gene/10090:Oc90 ^@ http://purl.uniprot.org/uniprot/Q80ZM2|||http://purl.uniprot.org/uniprot/Q9Z0L3 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Consists of 3 PA2-type domains.|||Expressed from embryonic day 9.5.|||In the embryo, highly expressed in the developing otocyst with weak expression in the brain. Also expressed in nonsensory epithelia of both the vestibular and cochlear portions of the developing inner ear. Not expressed in adult or embryonic macular sensory epithelia.|||Interacts with OTOL1.|||Major protein of the otoconia, a calcium carbonate structure in the saccule and utricle of the ear (PubMed:17300776). Together with OTOL1, acts as a scaffold for otoconia biomineralization: sequesters calcium and forms interconnecting fibrils between otoconia that are incorporated into the calcium crystal structure (PubMed:21655225, PubMed:24748133). Together with OTOL1, modulates calcite crystal morphology and growth kinetics (PubMed:24748133). It is unlikely that this protein has phospholipase A2 activity (PubMed:17300776).|||Otoconia show a strongly reduced matrix-calcium.|||Secreted http://togogenome.org/gene/10090:Hsd17b11 ^@ http://purl.uniprot.org/uniprot/Q9EQ06 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.|||Can convert androstan-3-alpha,17-beta-diol (3-alpha-diol) to androsterone in vitro, suggesting that it may participate in androgen metabolism during steroidogenesis. May act by metabolizing compounds that stimulate steroid synthesis and/or by generating metabolites that inhibit it. Has no activity toward DHEA (dehydroepiandrosterone), or A-dione (4-androste-3,17-dione), and only a slight activity toward testosterone to A-dione.|||Endoplasmic reticulum|||Expressed in the liver (at protein level) (PubMed:18359291). Also expressed in the intestine and, at much lower levels, in the kidney (PubMed:18359291).|||Lipid droplet http://togogenome.org/gene/10090:Svopl ^@ http://purl.uniprot.org/uniprot/Q6PDF3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Membrane http://togogenome.org/gene/10090:Hbs1l ^@ http://purl.uniprot.org/uniprot/L7N209|||http://purl.uniprot.org/uniprot/Q3TGM7|||http://purl.uniprot.org/uniprot/Q69ZS7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family.|||Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L. Interacts with the SKI complex.|||Cytoplasm|||Detected in embryos.|||Embryonic lethality; embryos fail to develop after 8.5 dpc (PubMed:33899734). Conditional deletion in the in the developing cerebellum and midbrain leads to severe development defects in the cerebellum characterized by the absence of multiple cell types (PubMed:33899734). In contrast, conditional deletion in the adult cerebellum and midbrain does not cause defects in neuron survival (PubMed:33899734). Defects are probably caused by ribosome pausing, due to inability to rescue stalled ribosomes (PubMed:33899734).|||GTPase component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway. The Pelota-HBS1L complex recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel. Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway. http://togogenome.org/gene/10090:Ssbp1 ^@ http://purl.uniprot.org/uniprot/Q8R2K3|||http://purl.uniprot.org/uniprot/Q9CYR0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA). In vitro, required to maintain the copy number of mitochondrial DNA (mtDNA) and plays a crucial role during mtDNA replication by stimulating the activity of the replisome components POLG and TWNK at the replication fork. Promotes the activity of the gamma complex polymerase POLG, largely by organizing the template DNA and eliminating secondary structures to favor ss-DNA conformations that facilitate POLG activity. In addition it is able to promote the 5'-3' unwinding activity of the mtDNA helicase TWNK. May also function in mtDNA repair.|||Expressed in all the layers of the retina (at protein level).|||Homotetramer. Interacts with MPG/AAG, through inhibition of its glycosylase activity it potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA. Interacts with POLDIP2. Interacts with PRIMPOL.|||Mitochondrion|||mitochondrion nucleoid http://togogenome.org/gene/10090:Kbtbd12 ^@ http://purl.uniprot.org/uniprot/Q9D618 ^@ Miscellaneous ^@ Due to intron retention. http://togogenome.org/gene/10090:Plat ^@ http://purl.uniprot.org/uniprot/P11214 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S1 family.|||Both FN1 and EGF-like domains are important for binding to LRP1.|||Both FN1 and one of the kringle domains are required for binding to fibrin.|||Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy (By similarity).|||Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Binds LRP1B; binding is followed by internalization and degradation. Forms heterodimer with SERPINA5 (By similarity). In complex with SERPINE1, interacts with SORL1 (By similarity).|||Inhibited by SERPINA5.|||The FN1 domain mediates binding to annexin A2.|||The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.|||The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-308 catalyzed by plasmin, tissue kallikrein or factor Xa.|||extracellular space http://togogenome.org/gene/10090:Src ^@ http://purl.uniprot.org/uniprot/P05480 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Dephosphorylated at Tyr-529 by PTPRJ (By similarity). Phosphorylated on Tyr-529 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-418. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-529, the SH3 domain engaged with the SH2-kinase linker, and Tyr-418 dephosphorylated. Dephosphorylation of Tyr-529 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-529, Tyr-418 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-529 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-74 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity (By similarity). Upon activation of IL6ST by IL6, Tyr-418 is phosphorylated and Tyr-529 dephosphorylated (PubMed:25731159).|||Displays enhanced levels of autophosphorylation at Tyr-418 compared to isoform 1.|||Displays reduced levels of autophosphorylation at Tyr-418 compared to isoform 2.|||Mitochondrion inner membrane|||Myristoylated at Gly-2, and this is essential for targeting to membranes.|||Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (By similarity). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (PubMed:9344858). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation (By similarity). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (By similarity). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-738'. Enhances RIGI-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-226'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (By similarity). Required for podosome formation (PubMed:21525037). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (By similarity).|||Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity.|||Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-418 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity).|||Nucleus|||Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on integrin mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Interacts with CDCP1, TGFB1I1 and TOM1L2 (By similarity). Interacts with DDEF1/ASAP1 via its SH3 domain (PubMed:9819391). Interacts with CCPG1 (PubMed:17000758). Interacts with the cytoplasmic domain of MUC1, phosphorylates it and increases binding of MUC1 with beta-catenin (By similarity). Interacts with RALGPS1 via its SH3 domain (By similarity). Interacts with CAV2 (tyrosine phosphorylated form) (By similarity). Interacts (via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation state of SRC C-terminus (By similarity). Interacts with FCAMR and PXN (By similarity). Interacts with ARRB2 (PubMed:19122674). Interacts with ARRB1 (By similarity). Interacts with SRCIN1 (By similarity). Interacts with NDFIP2 and more weakly with NDFIP1 (By similarity). Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1, ESR1 (dimethylated on arginine) and FAK (PubMed:14739300). Interacts (via SH2 and SH3 domain) with TNK2 (By similarity). Interacts (via protein kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt domain) (By similarity). Interacts with TRAF3 (via RING-type zinc finger domain) (By similarity). Interacts with RIGI, MAVS and TBK1 (By similarity). Interacts (via SH2 domain) with RACK1; the interaction is enhanced by tyrosine phosphorylation of RACK1 and inhibits SRC activity (By similarity). Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2 (PubMed:14739300). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated) (PubMed:16684964). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297). Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:12925710). Interacts with ERBB2 and STAT1 (PubMed:7542762, PubMed:9344858). Interacts with PDGFRA (tyrosine phosphorylated) (PubMed:14644164). Interacts with CSF1R (PubMed:7681396). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1 (By similarity). Interacts with DDR2 (By similarity). Interacts with AMOTL2; this interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites (By similarity). Interacts with DDR1 and DAB2 (PubMed:20093046). Interacts with TRAP1 (By similarity). Interacts with CBLC; the interaction is enhanced when SRC is phosphorylated at 'Tyr-424' (By similarity). Interacts with ARHGEF5 (PubMed:21525037). Interacts (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion (By similarity). Interacts with MPP2 (By similarity). Interacts with PRR7 (By similarity). Interacts (via kinase domain and to a lesser extent the SH2 domain) directly with PDLIM4; this interaction results in PTPN13-mediated dephosphorylation of this protein leading to its inactivation (By similarity). Interacts with P85 (PIK3R1 or PIK3R2) (By similarity). Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with IL6ST/gp130 (By similarity). Interacts (via SH3 domain) with PELP1 in the presence of 17-beta-estradiol (By similarity). Interacts with AMBRA1 (PubMed:28362576).|||Phosphorylation by CSK at Tyr-529 inhibits kinase activity. Inhibitory phosphorylation at Tyr-529 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-418 increases kinase activity.|||S-nitrosylation is important for activation of its kinase activity.|||Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-418 and may lead to lysosomal degradation (By similarity).|||cytoskeleton|||focal adhesion|||perinuclear region http://togogenome.org/gene/10090:Hoxc10 ^@ http://purl.uniprot.org/uniprot/P31257|||http://purl.uniprot.org/uniprot/Q8BZY5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Bpifb1 ^@ http://purl.uniprot.org/uniprot/Q61114 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Asymmetric expression in the embryonic node is dependent on Invs and Dnahc11.|||Belongs to the BPI/LBP/Plunc superfamily. Plunc family.|||Detectable in crown cells of the embryonic node from 7.5 dpc. Initial uniform expression develops asymmetrically with a higher level on the left side of the node until expression disappears around 13.5 dpc. Expressed in antrum pyloricum of the stomach from 11.5 dpc to 16.5 dpc and in dorsal tongue epithelium from 14.5 dpc to 16.5 dpc.|||Expressed in tongue, lung, thymus, and stomach. Expressed in epithelia of palate, anterior pharynx, trachea and upper bronchi. Expressed in distal tip of papillae in the anterior third of the tongue and in serous cells of von Ebner glands in the posterior third of the tongue. Expressed in columnar epithelium of the duodenum in embryonic gut at 16.5 dpc.|||May play a role in innate immunity in mouth, nose and lungs. Binds bacterial lipopolysaccharide (LPS) and modulates the cellular responses to LPS. May be involved in formation of the left-right axis in the node of the developing embryo.|||Secreted http://togogenome.org/gene/10090:Mterf4 ^@ http://purl.uniprot.org/uniprot/D3Z3A2|||http://purl.uniprot.org/uniprot/Q8BVN4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ablation of the gene is not viable. At 8.5 dpc, mutant homozygous embryos exhibit much reduced size, lack of heart and no optic disks. Conditional knockout in heart leads to severe mitochondrial cardiomyopathy. Premature death occurs at about 21 weeks and decreased body weight is observed from 15 weeks until death.|||Belongs to the mTERF family.|||Heterodimer with NSUN4; this interaction may be required for NSUN4 recruitment to the mitochondrial large ribosomal subunit.|||Mitochondrion|||Regulator of mitochondrial ribosome biogenesis and translation. Binds to mitochondrial ribosomal RNAs 16S, 12S and 7S (By similarity). Targets NSUN4 RNA methyltransferase to the mitochondrial large ribosomal subunit.|||The MTERF repeats form a half-donut shaped, right-handed superhelix, where the concave side displays a positively charged path for nucleic acid interaction.|||Widely expressed, with highest levels in liver, followed by testis, kidney and brain. http://togogenome.org/gene/10090:Or6z6 ^@ http://purl.uniprot.org/uniprot/Q8VF33 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or10v9 ^@ http://purl.uniprot.org/uniprot/Q7TQS3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ascc1 ^@ http://purl.uniprot.org/uniprot/Q9D8Z1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in 17.5-day-old embryos.|||Expressed in the spinal cord, brain, paraspinal ganglia, thyroid, and submandibular glands.|||Identified in the ASCC complex that contains ASCC1, ASCC2 and ASCC3. Interacts directly with ASCC3. The ASCC complex interacts with ALKBH3. Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3. Interacts with CSRP1. Interacts with ZCCHC4 (By similarity).|||Nucleus|||Nucleus speckle|||Plays a role in DNA damage repair as component of the ASCC complex. Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation. In cells responding to gastrin-activated paracrine signals, it is involved in the induction of SERPINB2 expression by gastrin. May also play a role in the development of neuromuscular junction. http://togogenome.org/gene/10090:Oxsm ^@ http://purl.uniprot.org/uniprot/Q9D404 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP synthases family.|||Inhibited by cerulenin.|||May play a role in the biosynthesis of lipoic acid as well as longer chain fatty acids required for optimal mitochondrial function.|||Mitochondrion http://togogenome.org/gene/10090:Trpv2 ^@ http://purl.uniprot.org/uniprot/Q9WTR1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in spleen, placenta, skeleton muscle, lung and brain.|||Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV2 sub-subfamily.|||Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH.|||Cell membrane|||Cytoplasm|||Homotetramer (Probable). Interacts with a cAMP-dependent protein kinase type II regulatory subunit (PRKAR2A or PRKAR2B) and ACBD3. Interacts with SLC50A1; the interaction probably occurs intracellularly and depends on TRPV2 N-glycosylation (By similarity).|||Melanosome|||N-glycosylated.|||Phosphorylated by PKA. http://togogenome.org/gene/10090:Kcnab1 ^@ http://purl.uniprot.org/uniprot/A0A5F8MPA4|||http://purl.uniprot.org/uniprot/P63143|||http://purl.uniprot.org/uniprot/Q3U6C5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shaker potassium channel beta subunit family.|||Cell membrane|||Cytoplasm|||Cytoplasmic potassium channel subunit that modulates the characteristics of the channel-forming alpha-subunits (PubMed:10454353). Modulates action potentials via its effect on the pore-forming alpha subunits (PubMed:10454353). Promotes expression of the pore-forming alpha subunits at the cell membrane, and thereby increases channel activity (PubMed:8824288). Mediates closure of delayed rectifier potassium channels by physically obstructing the pore via its N-terminal domain and increases the speed of channel closure for other family members (By similarity). Promotes the closure of KCNA1, KCNA2 and KCNA5 channels (By similarity). Accelerates KCNA4 channel closure (By similarity). Accelerates the closure of heteromeric channels formed by KCNA1 and KCNA4 (By similarity). Accelerates the closure of heteromeric channels formed by KCNA2, KCNA5 and KCNA6 (By similarity). Enhances KCNB1 and KCNB2 channel activity (PubMed:8824288). Binds NADPH; this is required for efficient down-regulation of potassium channel activity (By similarity). Has NADPH-dependent aldoketoreductase activity (By similarity). Oxidation of the bound NADPH strongly decreases N-type inactivation of potassium channel activity (By similarity).|||Detected in brain, in hippocampus and striatum (at protein level) (PubMed:10454353). Predominantly expressed in brain. No expression found in heart, skeletal muscle or kidney. In the late embryonic and early neonatal brain, highly expressed in hippocampus, cerebral cortex, caudate putamen, colliculus and cerebellum.|||Expressed from embryonic day 16. Expressed throughout embryonic development, in neonate and in adult.|||Homotetramer (By similarity). Interaction with tetrameric potassium channel alpha subunits gives rise to a heterooctamer (Probable). Identified in potassium channel complexes containing KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNAB1 and KCNAB2 (By similarity). Interacts with KCNA1 (By similarity). Interacts with the dimer formed by GNB1 and GNG2; this enhances KCNA1 binding (By similarity). Interacts with KCNA4 (By similarity). Interacts with KCNB2 and KCNA5 (PubMed:8824288). Interacts with SQSTM1 (By similarity). Part of a complex containing KCNA1, KCNA4 and LGI1; interaction with LGI1 inhibits down-regulation of KCNA1 channel activity (By similarity).|||Membrane|||Mutant mice show subtle defects in learning (PubMed:10454353). Such learning impairments are not detectable in older mice and are not observed when mice are kept in a stimulating environment (PubMed:14511342, PubMed:15530391).|||The N-terminal domain of the beta subunit mediates closure of delayed rectifier potassium channels by physically obstructing the pore. http://togogenome.org/gene/10090:Abhd17a ^@ http://purl.uniprot.org/uniprot/Q99JW1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. ABHD17 family.|||Cell membrane|||Endosome membrane|||Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards NRAS. Has depalmitoylating activity towards DLG4/PSD95. May have depalmitoylating activity towars MAP6.|||Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization. Palmitoylation is required for post-synaptic localization and for depalmitoylating activity towards DLG4/PSD95.|||Postsynaptic density membrane|||dendritic spine http://togogenome.org/gene/10090:Hcrt ^@ http://purl.uniprot.org/uniprot/O55241|||http://purl.uniprot.org/uniprot/Q547R2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the orexin family.|||Binds to orexin receptor HCRTR2/OX2R only (By similarity). Stimulates food intake (By similarity). Modulates pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner (By similarity).|||Binds to orexin receptors HCRTR1/OX1R and HCRTR2/OX2R with a high affinity (By similarity). Stimulates food intake (By similarity). Modulates pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner (By similarity).|||Cytoplasmic vesicle|||Endoplasmic reticulum|||Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested.|||Restricted to neuronal cell bodies of the dorsal and lateral hypothalamus.|||Rough endoplasmic reticulum|||Specific enzymatic cleavages at paired basic residues yield the different active peptides.|||Synapse|||Vesicle http://togogenome.org/gene/10090:Ache ^@ http://purl.uniprot.org/uniprot/P21836|||http://purl.uniprot.org/uniprot/Q543Z1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Cell membrane|||Isoform H generates GPI-anchored dimers; disulfide linked. Isoform T generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, isoform T subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers, from monomers and dimers (By similarity). Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers.|||Predominates in most expressing tissues except erythrocytes where a glycophospholipid-attached form of ACHE predominates.|||Secreted|||Synapse|||Synapses usually contain asymmetric molecules of cholinesterase, with a collagen-like part disulfide-bonded to the catalytic part. A different, globular type of cholinesterase occurs on the outer surfaces of cell membranes, including those of erythrocytes.|||Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft.|||This is the catalytic subunit of an asymmetric or soluble form of ACHE. http://togogenome.org/gene/10090:Steep1 ^@ http://purl.uniprot.org/uniprot/Q8VDP2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STEEP1 family.|||Cytoplasm|||Expressed in neurons in the brain cortex and cerebellum (at protein level).|||Interacts with STING1, PIK3C3, and ATG14; the STING1/STEEP1 interaction is increased upon STING1 cGAMP-activation and leads to recruitment of PI3K complex I.|||Nucleus|||Stimulates membrane curvature formation and subsequent endoplasmic reticulum exit site (ERES) establishment by recruiting PI3K complex I, leading to COPII vesicle-mediated transport (By similarity). Promotes endoplasmic reticulum (ER) exit of cGAMP-activated STING1 oligomers (PubMed:32690950). http://togogenome.org/gene/10090:Pacsin1 ^@ http://purl.uniprot.org/uniprot/Q3TYF2|||http://purl.uniprot.org/uniprot/Q543Y7|||http://purl.uniprot.org/uniprot/Q61644 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PACSIN family.|||Binds to membranes via its F-BAR domain and mediates membrane tubulation. Plays a role in the reorganization of the microtubule cytoskeleton via its interaction with MAPT; this decreases microtubule stability and inhibits MAPT-induced microtubule polymerization. Plays a role in cellular transport processes by recruiting DNM1, DNM2 and DNM3 to membranes. Plays a role in the reorganization of the actin cytoskeleton and in neuron morphogenesis via its interaction with COBL and WASL, and by recruiting COBL to the cell cortex. Plays a role in the regulation of neurite formation, neurite branching and the regulation of neurite length. Required for normal synaptic vesicle endocytosis; this process retrieves previously released neurotransmitters to accommodate multiple cycles of neurotransmission. Required for normal excitatory and inhibitory synaptic transmission.|||Cell membrane|||Cell projection|||Cytoplasm|||Cytoplasmic vesicle membrane|||Expression is seen at embryonic day 17 and is up-regulated developmentally with a correlation to neuronal differentiation.|||Highly expressed in brain. Detected in hippocampus and dorsal root ganglion neurons. Detected in rod photoreceptor terminals in the outer plexiform layer of the retina (at protein level). In CNS neurons, high levels in the pyramidal cells of the hippocampus, Purkinje cells of the cerebellum and large neurons of the cortex and brain stem.|||Homodimer. May form heterooligomers with other PACSINs. Interacts with both COBL and DBNL. Identified in a complex composed of COBL, PACSIN1 and WASL. Interacts with EHD3 (By similarity). Interacts (via SH3 domain) with SYNJ1 and WASL. Interacts (via SH3 domain) with DNM1; the interaction is reduced by DNM1 phosphorylation. Interacts with DNM2 and DNM3. Interacts with MAPT. Interacts with EHD1. Interacts with TRPV4.|||Membrane|||Mice are born at the expected Mendelian rate, but display a slightly reduced body weight and reduced fertility. Mice display increased synaptic vesicle diameter and impaired compensatory synaptic vesicle endocytosis after high synapse activity. Rod photoreceptor ribbon synapses display an abnormally high number of endosome-like structures and tubular elements after light exposure. Mice display defects in excitatory and inhibitory synaptic transmission in the hippocampus, and display a tendency to seizures when confronted with novelty.|||Phosphorylated by casein kinase 2 (CK2) and protein kinase C (PKC).|||Synapse|||The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain. DNM1 binding abolishes autoinhibition.|||cytosol|||ruffle membrane|||synaptosome http://togogenome.org/gene/10090:Siglece ^@ http://purl.uniprot.org/uniprot/Q91Y57 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.|||Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Expressed by monocytic/myeloid lineage cells. Found at higher levels in spleen, liver and heart. Found at lower levels in kidney and lung.|||Homodimer; disulfide-linked. Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation.|||Membrane|||Phosphorylation of Tyr-432 is required for binding to PTPN6 and PTPN11. Phosphorylation of Tyr-455 is involved in binding to PTPN6. Tyr-432 needs to be phosphorylated prior to Tyr-455.|||Putative adhesion molecule that mediates sialic-acid dependent binding to cells. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. http://togogenome.org/gene/10090:Nr1d1 ^@ http://purl.uniprot.org/uniprot/Q3UV55 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Binds DNA as a monomer or a homodimer (By similarity). Interacts with NR2E3 and ZNHIT1 (By similarity). Interacts with C1D (PubMed:9405624). Interacts with SP1 (PubMed:22549838). Interacts with OPHN1 (via C-terminus) (PubMed:21874017). Interacts with PER2; the interaction associates PER2 to BMAL1 promoter region (PubMed:20159955, PubMed:22170608). Interacts with CRY1 (By similarity). Interacts with CCAR2 (PubMed:23398316). Interacts with SIAH2 (By similarity). Interacts with FBXW7 and CDK1 (PubMed:27238018). Interacts with HUWE1 (By similarity). Interacts with NR0B2 (PubMed:25212631, PubMed:30555544). Interacts with NFIL3 (PubMed:29653076). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (PubMed:27686098).|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||During development at embryonic day 18.5 dpc, expressed in the outer neuroblastic layer of the retina where developing postmitotic photoreceptors and retinal progenitors reside (at protein level).|||Expressed during adipocyte differentiation (at protein level). Expressed in skeletal muscle, bladder, lumbar spinal cord, pancreatic islets and hypothalamus. Expressed in developing and adult retina. In the adult retina, predominantly expressed in the outer nuclear layer, where rod and cone cells reside, and also localized to the ganglion cell layer. Expressed in a circadian manner in the liver (PubMed:27686098). Expressed in a circadian manner in the lung with a peak between ZT8 and ZT12 (PubMed:29533925).|||Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues. In bladder smooth muscle cells, pancreas and lumbar spinal cord, exhibits night/day variations with a peak time at circadian time (CT) 4-12 and a trough at CT16-24.|||Mice display increased cold tolerance, higher oxygen consumption rates, enhanced brown adipose tissue metabolic capacity, maintenance of higher body temperature throughout the light phase and increased glucose uptake only during the day. They also show retinal abnormalities such as pan-retinal spotting and decreased response to light and decreased bile acid accumulation. Double knockout for NR1D1 and PER2 show a significantly shorter period length compared with wild type or single knockouts for both genes. 50% of double knockouts animals show a stable circadian throughout at least 5 weeks in constant darkness. The other 50% of animals lose their circadian rhythmicity when held in constant darkness for an average of 21 days. Animals have blunted steady-state levels of glycogen in the liver in spite of normal patterns of food consumption. Mice show exaggerated pulmonary inflammatory responses (PubMed:29533925). Mice display enhanced spontaneous hippocampal microglial and astrocyte activation, increased microglial NF-kappaB signaling and exacerbated LPS-induced neuroinflammation in the hippocampus (PubMed:30792350). Conditional knockout of both NR1D1 and NR1D2 in bronchiolar epithelial cells abolished diurnal rhythmicity of PER2 in the bronchioles and increased inflammatory responses and chemokine activation (PubMed:29533925).|||Nucleus|||Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization.|||Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a prerequisite to its ubiquitination.|||Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC1 and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (PubMed:30555544). Represses the transcription of CES2 (PubMed:29653076). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (PubMed:24794873). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (PubMed:27686098). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (PubMed:29533925). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (PubMed:30792350). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (PubMed:30096135).|||Ubiquitinated, leading to its proteasomal degradation (PubMed:20534529). Ubiquitinated by the SCF(FBXW7) complex when phosphorylated by CDK1 leading to its proteasomal degradation (PubMed:27238018). Ubiquitinated by SIAH2; leading to its proteasomal degradation (By similarity). Rapidly ubiquitinated in response to inflammatory triggers and sumoylation is a prerequisite to its ubiquitination (PubMed:29533925).|||Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Sprr2d ^@ http://purl.uniprot.org/uniprot/O70555 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane (By similarity).|||Cytoplasm|||During early pregnancy, uterine expression is markedly increased at 1 dpc and 2 dpc, with levels decreasing from 3 dpc onwards.|||Expressed in uterus.|||Up-regulated by estrogen in the uterus of ovariectomized animals, with strongly increased expression detected in luminal epithelial cells at 6 and 12 hours after hormone injection. http://togogenome.org/gene/10090:Myog ^@ http://purl.uniprot.org/uniprot/P12979 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation, cell cycle exit and muscle atrophy. Essential for the development of functional embryonic skeletal fiber muscle differentiation. However is dispensable for postnatal skeletal muscle growth; phosphorylation by CAMK2G inhibits its transcriptional activity in respons to muscle activity. Required for the recruitment of the FACT complex to muscle-specific promoter regions, thus promoting gene expression initiation. During terminal myoblast differentiation, plays a role as a strong activator of transcription at loci with an open chromatin structure previously initiated by MYOD1. Together with MYF5 and MYOD1, co-occupies muscle-specific gene promoter core regions during myogenesis. Cooperates also with myocyte-specific enhancer factor MEF2D and BRG1-dependent recruitment of SWI/SNF chromatin-remodeling enzymes to alter chromatin structure at myogenic late gene promoters. Facilitates cell cycle exit during terminal muscle differentiation through the up-regulation of miR-20a expression, which in turn represses genes involved in cell cycle progression. Binds to the E-box containing (E1) promoter region of the miR-20a gene. Plays also a role in preventing reversal of muscle cell differentiation. Contributes to the atrophy-related gene expression in adult denervated muscles. Induces fibroblasts to differentiate into myoblasts.|||Display normal myoblast formation during embryogenesis, but show perinatal lethality because of a deficiency during the later stages of skeletal muscle fiber formation. Show no abnormalities for smooth muscles and cardiocytes differentiation. Conditional mutant with expression abrogated in muscle cells from 15.5 or 17.5 dpc are viable, fertil and exhibit no noticeable muscle growth and reduction of myofiber diameter defects but show smaller body size and mass. Conditional mutant in muscle cells of denervated hindlimb muscles show an inhibition of the denervation-dependent reductions in mass, force and atrophy of slow fiber-type soleus muscles, without increased in satellite cell proliferation and fusion.|||Expressed in myoblast cells. Expressed weakly in myotubes (at protein level). Expressed strongly in denervated muscles and in satellite cells isolated from denervated muscles. Expressed weakly in innervated muscle and in satellite cells isolated from innervated muscles.|||Expressed in the myotome of the somites at 8.5 dpc, onward (at protein level). Expressed in proximal region of both the hindlimb and the forelimb at 11.5 dpc, onward. Expressed during muscle maturation between 15 and 17 dpc and decreases thereafter. Not detected within the heart.|||Homodimer and heterodimer with E12; heterodimerization enhances MYOG DNA-binding and transcriptional activities. Interacts with SMARCA4/BRG1/BAF190A. Interacts (via C-terminal region) with SSRP1 and SUPT16H; the interaction is indicative of an interaction with the FACT complex. nteracts with CSRP3 (By similarity).|||Nucleus|||Phosphorylated by CAMK2G on threonine and serine amino acids in a muscle activity-dependent manner. Phosphorylation of Thr-87 impairs both DNA-binding and trans-activation functions in contracting muscles (By similarity).|||Up-regulated in denervated muscles (at protein level). Up-regulated during myogenesis in the embryo and in cell culture models of myogenic differentiation via the p38 MAPK signaling pathway. http://togogenome.org/gene/10090:Mzt1 ^@ http://purl.uniprot.org/uniprot/Q8BUR9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MOZART1 family.|||Part of the gamma-tubulin complex. Interacts with TUBG1.|||Required for gamma-tubulin complex recruitment to the centrosome.|||centrosome|||spindle http://togogenome.org/gene/10090:Gzmc ^@ http://purl.uniprot.org/uniprot/P08882 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytolytic granule|||This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. http://togogenome.org/gene/10090:Celf2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J2B0|||http://purl.uniprot.org/uniprot/E9QA47|||http://purl.uniprot.org/uniprot/Q9Z0H4|||http://purl.uniprot.org/uniprot/S4R1S7 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CELF/BRUNOL family.|||Cytoplasm|||Expressed in heart, muscle, brain, liver, thigh, stomach and lung at 14 dpc (at protein level). Expressed in embryo at 7, 11 and 17 dpc. Expressed in the developing central nervous system from 12 to 16 dpc.|||Expressed in tongue, spleen and brain (at protein level). Expressed in liver, thigh, stomach, lung and heart to very low levels (at protein level). Expressed in heart, brain, lung and muscle.|||Gene prediction based on similarity to rat ortholog.|||Interacts with A1CF.|||Nucleus|||RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing (By similarity). Specifically activates exon 5 inclusion of TNNT2 in embryonic, but not adult, skeletal muscle (By similarity). Activates TNNT2 exon 5 inclusion by antagonizing the repressive effect of PTB (By similarity). Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs (By similarity). Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre-mRNA (By similarity). Involved in the apoB RNA editing activity (By similarity). Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury. Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression. Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK (By similarity). Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5 (By similarity). Binds preferentially to UG-rich sequences, in particular UG repeat and UGUU motifs (By similarity). Binds to apoB mRNA, specifically to AU-rich sequences located immediately upstream of the edited cytidine (By similarity). Binds AU-rich sequences in the 3'-UTR of COX2 mRNA. Binds to an intronic RNA element responsible for the silencing of exon 21 splicing. Binds to (CUG)n repeats. May be a specific regulator of miRNA biogenesis. Binds to primary microRNA pri-MIR140 and, with CELF1, negatively regulates the processing to mature miRNA (By similarity).|||Up-regulated following ionizing radiation in the crypt epithelial cells of the intestin. Down-regulated by bacterial lipopolysaccharides (LPS). Down-regulated by prostaglandin E2 following ionizing radiation. http://togogenome.org/gene/10090:Ccnb1 ^@ http://purl.uniprot.org/uniprot/P24860|||http://purl.uniprot.org/uniprot/Q3TQW9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accumulates steadily during G2 and is abruptly destroyed at mitosis.|||Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin AB subfamily.|||Cytoplasm|||Essential for the control of the cell cycle at the G2/M (mitosis) transition.|||Interacts with the CDC2 protein kinase to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex. Binds HEI10. Interacts with catalytically active RALBP1 and CDC2 during mitosis to form an endocytotic complex during interphase. Interacts with CCNF; interaction is required for nuclear localization. Interacts with CDK5RAP3 (By similarity). Interacts with RFPL4A and UBE2A (PubMed:12525704). Interacts with INCA1 (By similarity).|||Nucleus|||Phosphorylated by PLK1 at Ser-130 on centrosomes during prophase: phosphorylation by PLK1 does not cause nuclear import. Phosphorylation at Ser-144 was also reported to be mediated by PLK1 but Ser-130 seems to be the primary phosphorylation site (By similarity).|||Ubiquitinated by the SCF(NIPA) complex during interphase, leading to its destruction. Not ubiquitinated during G2/M phases (By similarity).|||centrosome http://togogenome.org/gene/10090:Pid1 ^@ http://purl.uniprot.org/uniprot/Q3UBG2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with LRP1 and CUBN.|||Increases proliferation of preadipocytes without affecting adipocytic differentiation. http://togogenome.org/gene/10090:Emb ^@ http://purl.uniprot.org/uniprot/P21995 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At neuromuscular junctions, 5-fold higher expression levels at P0 compared to adult.|||Cell membrane|||Interacts with SLC16A1, SLC16A6 and SLC16A7.|||Only member of the immunoglobulin superfamily to be expressed in embryonal carcinoma cells, which resemble multipotential cells of early embryos.|||Plays a role in targeting the monocarboxylate transporters SLC16A1, SLC16A6 and SLC16A7 to the cell membrane (By similarity). Plays a role in the outgrowth of motoneurons and in the formation of neuromuscular junctions. Following muscle denervation, promotes nerve terminal sprouting and the formation of additional acetylcholine receptor clusters at synaptic sites without affecting terminal Schwann cell number or morphology. Delays the retraction of terminal sprouts following re-innervation of denervated endplates.|||Regulated by muscle activity. Strongly up-regulated after muscle denervation, including that of gastrocnemius muscle. Maximal expression is observed 10 days after denervation (at protein level).|||Synapse http://togogenome.org/gene/10090:Arpc1b ^@ http://purl.uniprot.org/uniprot/Q9WV32 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat ARPC1 family.|||Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC.|||Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility. In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Cyp4a10 ^@ http://purl.uniprot.org/uniprot/O88833 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long-chain fatty acids (By similarity). Acts as a major omega-hydroxylase for dodecanoic (lauric) acid in liver (PubMed:17112342) (By similarity). In kidney, may play an important role in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (By similarity). Also participates in the formation of anti-inflammatory hydroxyepoxyeicosatrienoic acids (HEETs) in kidney by converting 8,9-epoxyeicosatrienoic acid (EET) to 20,8,9-HEET, an activator of PPARA. Displays substantially lower fatty acid omega-1 hydroxylase activity (By similarity). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highly expressed in the kidneys of both genders.|||Microsome membrane|||Mutant mice are hypertensive due to constitutive activation of renal epithelial sodium channels and increased sodium reabsorption. http://togogenome.org/gene/10090:Fsbp ^@ http://purl.uniprot.org/uniprot/Q8BKE5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with APBA1 (via PDZ 1 and 2 domains).|||Nucleus|||Transcriptional repressor that down-regulates the expression of the fibrinogen gamma chain. Represses transcription of GSK3B gene promoter via its interaction with APBA1. http://togogenome.org/gene/10090:Agtrap ^@ http://purl.uniprot.org/uniprot/Q9WVK0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Appears to be a negative regulator of type-1 angiotensin II receptor-mediated signaling by regulating receptor internalization as well as mechanism of receptor desensitization such as phosphorylation. Induces also a decrease in angiotensin II-stimulated transcriptional activity. May play a role of negative regulator in cardiomyocyte hypertrophy induced by angiotensin II through an inhibition of p38 mitogen-activated protein kinase pathway.|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with RACK1 (By similarity), and with the C-terminal region of AGTR1.|||Ubiquitous but more abundant in kidney, testis and heart. http://togogenome.org/gene/10090:Gprc5c ^@ http://purl.uniprot.org/uniprot/I7HPW4|||http://purl.uniprot.org/uniprot/J3JS84|||http://purl.uniprot.org/uniprot/Q8K3J9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Membrane|||This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways. http://togogenome.org/gene/10090:Tbc1d4 ^@ http://purl.uniprot.org/uniprot/Q8BYJ6 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake (By similarity).|||Phosphorylated by AKT1; insulin-induced. Also phosphorylated by AMPK in response to insulin. Insulin-stimulated phosphorylation is required for SLC2A4/GLUT4 translocation. Has no effect on SLC2A4/GLUT4 internalization.|||Widely expressed, including in pancreatic beta cells. http://togogenome.org/gene/10090:Ube2j1 ^@ http://purl.uniprot.org/uniprot/Q9JJZ4 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Catalyzes the covalent attachment of ubiquitin to other proteins. Functions in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD) and is essential for cells to recover from ER stress. Plays a role in MAPKAPK2-dependent translational control of TNF-alpha synthesis. Acts also as a platform for perinuclear positioning of the endosomal system by mediating ubiquitination of SQSTM1 through interaction with the E3 ubiquitin-protein ligase RNF26.|||Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1. Interacts with E3 ligase RNF26.|||Deletion mice have reduced viability and fail to thrive early after birth. Specific components of the ER dislocation machinery are up-regulated. In addition, males are sterile due to a defect in late spermatogenesis.|||Endoplasmic reticulum membrane|||Phosphorylated UBE2J1 is rapidly ubiquitinated and subsequently degraded by the proteasome.|||Phosphorylated at Ser-184 in a cytosolic stress-dependent manner by MAP kinase p38 MAPKAPK2. http://togogenome.org/gene/10090:Sprr2k ^@ http://purl.uniprot.org/uniprot/G5E8D1|||http://purl.uniprot.org/uniprot/O70562 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane (By similarity).|||Cytoplasm|||Not expressed in uterus. http://togogenome.org/gene/10090:Elf3 ^@ http://purl.uniprot.org/uniprot/Q3UPW2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Cytoplasm|||Expressed in small intestine, colon, lung, kidney and uterus. Also expressed in the corneal epithelium and conjunctiva of the developing and adult eye. Not detected in liver, spleen, thymus, brain, heart, skeletal muscle or ovary.|||Expression in HC11 cells from midpregnant mouse mammary epithelium increases upon reaching lactogenic competency, and is down-regulated upon exposure to lactogenic hormones that induce milk protein (Beta-casein) expression. Up-regulated upon differentiation in corneal epithelium.|||Expression increases progressively from 7 dpc and is detectable in virgin mammary glands, then shows little if any change during pregnancy and declines to barely detectable levels after 3 days of lactation. Detected from 13.5 dpc in conjunctiva epithelium. In cornea, a weak signal is detected at 16.5 dpc and persists throughout the later stages of development.|||Interacts with TBP. Interacts with CREBBP and EP300; these act as transcriptional coactivators of ELF3 and positively modulate its function. Interacts with XRCC5/KU86 and XRCC6/KU70; these inhibit the ability of ELF3 to bind DNA and negatively modulate its transcriptional activity. Associated with CLND7 and POU2F3 (By similarity). Interacts with ZNF768 (By similarity).|||Mice show about 30% fetal lethality at around 11.5 dpc. Approximately 70% of the mutant progeny are born and display severe alterations in tissue architecture in the small intestine. Elf3-deficient enterocytes express markedly reduced levels of TGFBR2.|||Nucleus|||Transcriptional activator that binds and transactivates ETS sequences containing the consensus nucleotide core sequence GGA[AT]. Acts synergistically with POU2F3 to transactivate the SPRR2A promoter and with RUNX1 to transactivate the ANGPT1 promoter (By similarity). Also transactivates collagenase, CCL20, CLND7, FLG, KRT8, NOS2, PTGS2, SPRR2B, TGFBR2 and TGM3 promoters. Represses KRT4 promoter activity (By similarity). Involved in mediating vascular inflammation. May play an important role in epithelial cell differentiation and tumorigenesis. May be a critical downstream effector of the ERBB2 signaling pathway (By similarity). May be associated with mammary gland development and involution. Plays an important role in the regulation of transcription with TATA-less promoters in preimplantation embryos, which is essential in preimplantation development. http://togogenome.org/gene/10090:Ffar4 ^@ http://purl.uniprot.org/uniprot/Q3V2S5|||http://purl.uniprot.org/uniprot/Q7TMA4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice show glucose intolerance, hyperinsulinemia and display insulin (INS) resistance and a reduced preference for fatty acids (PubMed:22343897, PubMed:24742677, PubMed:20573884). When fed a high-fat diet, they develop obesity and have fatty liver with decreased adipocyte differentiation and lipogenesis, and enhanced hepatic lipogenesis (PubMed:22343897). INS resistance in such mice is associated with reduced INS signaling and enhanced inflammation in adipose tissue (PubMed:20813258).|||Endosome membrane|||Expression detected in differentiated mature adipocytes, with levels increasing during late stage adipocyte differentiation (PubMed:17250804, PubMed:29343498). Low expression is detected in preadipocytes, mainly localized in primary cilium (PubMed:31761534). Expression level in bone marrow mesenchymal stem cells is gradually increased during differentiation toward osteoblasts (PubMed:26365922).|||G-protein-coupled receptor for long-chain fatty acids (LCFAs) with a major role in adipogenesis, energy metabolism and inflammation. Signals via G-protein and beta-arrestin pathways (PubMed:27852822, PubMed:26873857). LCFAs sensing initiates activation of phosphoinositidase C-linked G proteins GNAQ and GNA11 (G(q)/G(11)), inducing a variety of cellular responses via second messenger pathways such as intracellular calcium mobilization, modulation of cyclic adenosine monophosphate (cAMP) production, and mitogen-activated protein kinases (MAPKs) (PubMed:27852822, PubMed:26873857). After LCFAs binding, associates with beta-arrestin ARRB2 that acts as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:27852822, PubMed:26873857). In response to dietary fats, plays an important role in the regulation of adipocyte proliferation and differentiation (PubMed:17250804, PubMed:22343897, PubMed:27853148, PubMed:29343498, PubMed:31761534). Acts as a receptor for omega-3 polyunsaturated fatty acids (PUFAs) at primary cilium of perivascular preadipocytes, initiating an adipogenic program via cAMP and CTCF-dependent chromatin remodeling that ultimately results in transcriptional activation of adipogenic genes and cell cycle entry (PubMed:31761534). Induces differentiation of brown and beige adipocytes probably via autocrine and endocrine functions of FGF21 hormone (PubMed:27853148, PubMed:29343498). Contributes to the thermogenic activation of brown adipose tissue and the browning of white adipose tissue (PubMed:27853148, PubMed:29343498). Activates brown adipocytes by initiating intracellular calcium signaling leading to mitochondrial depolarization and fission, and overall increased mitochondrial respiration (PubMed:29343498). Consequently stimulates fatty acid uptake and oxidation in mitochondria together with UCP1-mediated thermogenic respiration, eventually reducing fat mass (PubMed:29343498). Regulates bi-potential differentiation of bone marrow mesenchymal stem cells toward osteoblasts or adipocytes likely by up-regulating distinct integrins (PubMed:26365922). In response to dietary fats regulates hormone secretion and appetite (PubMed:15619630, PubMed:25535828, PubMed:24742677, PubMed:24663807, PubMed:24222669). Stimulates GIP and GLP1 secretion from enteroendocrine cells as well as GCG secretion in pancreatic alpha cells, thereby playing a role in the regulation of blood glucose levels (PubMed:15619630, PubMed:25535828, PubMed:24742677). Negatively regulates glucose-induced SST secretion in pancreatic delta cells (PubMed:24663807). Mediates LCFAs inhibition of GHRL secretion, an appetite-controlling hormone (PubMed:24222669). In taste buds, contributes to sensing of dietary fatty acids by the gustatory system (PubMed:20573884). During the inflammatory response, promotes anti-inflammatory M2 macrophage differentiation in adipose tissue (PubMed:20813258). Mediates the anti-inflammatory effects of omega-3 PUFAs via inhibition of NLRP3 inflammasome activation (By similarity). In this pathway, interacts with adapter protein ARRB2 and inhibits the priming step triggered by Toll-like receptors (TLRs) at the level of TAK1 and TAB1 (PubMed:20813258). Further inhibits the activation step when ARRB2 directly associates with NLRP3, leading to inhibition of pro-inflammatory cytokine release (By similarity). Mediates LCFAs anti-apoptotic effects (PubMed:15774482).|||Highly expressed in brown and white adipose tissue (PubMed:27853148, PubMed:17250804, PubMed:24222669). Expressed in perivascular ciliated preadipocytes (at protein level) (PubMed:31761534). Expressed in the taste buds of the circumvallate and fungiform papillae, mainly in type II cells (at protein level) (PubMed:19071193, PubMed:20573884). Abundant expression is detected in the gastrointestinal tract (PubMed:15619630, PubMed:27853148, PubMed:17250804, PubMed:24222669). Highly expressed in lung and pituitary gland (PubMed:15619630, PubMed:17250804). Expressed in enteroendocrine K cells of the upper small intestine (PubMed:25535828). Expressed in alpha and delta cells of pancreatic islets (PubMed:24742677, PubMed:24663807). Expressed in pro-inflammatory CD11C-positive macrophages (PubMed:20813258). Also expressed in spleen (PubMed:17250804).|||Interacts (via C-terminus) with ARRB2 following LCFAs stimulation.|||Lysosome membrane|||Membrane|||Phosphorylated at two clusters of Ser and Thr residues located in the intracellular C-terminus, a prerequisite for FFAR4 internalization via an ARRB2-dependent pathway.|||Up-regulated in response to high-fat diet in adipose tissue macrophages and in hepatic Kupffer cells (PubMed:17250804, PubMed:20813258). Up-regulated in response to either short- or long-term cold exposure in brown adipose tissue and inguinal white adipose tissue (PubMed:27853148). Up-regulated by ADRB3 agonist (PubMed:29343498).|||cilium membrane http://togogenome.org/gene/10090:Amer3 ^@ http://purl.uniprot.org/uniprot/Q6NS69 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Amer family.|||Cell membrane|||Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane (By similarity). http://togogenome.org/gene/10090:App ^@ http://purl.uniprot.org/uniprot/A0A2I3BPT1|||http://purl.uniprot.org/uniprot/A0A2I3BQZ9|||http://purl.uniprot.org/uniprot/P12023|||http://purl.uniprot.org/uniprot/Q3TWF3|||http://purl.uniprot.org/uniprot/Q6GR78 ^@ Caution|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Amyloid-beta peptides are degraded by IDE.|||Amyloid-beta peptides are lipophilic metal chelators with metal-reducing activity. Binds transient metals such as copper, zinc and iron. Rat and mouse amyloid-beta peptides bind only weakly transient metals and have little reducing activity due to substitutions of transient metal chelating residues. Amyloid-beta protein 42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Also binds GPC1 in lipid rafts (By similarity).|||Belongs to the APP family.|||Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB family members, the APBA family, MAPK8IP1, SHC1, NUMB and DAB1. Binding to DAB1 inhibits its serine phosphorylation. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Also interacts with GPCR-like protein BPP, APPBP1, IB1, KNS2 (via its TPR domains), APPBP2 (via BaSS) and DDB1 (By similarity). In vitro, it binds MAPT via the MT-binding domains (By similarity). Associates with microtubules in the presence of ATP and in a kinesin-dependent manner (By similarity). Interacts, through a C-terminal domain, with GNAO1 (By similarity). Amyloid-beta protein 42 binds CHRNA7 in hippocampal neurons (By similarity). Amyloid-beta associates with HADH2 (By similarity). Interacts with ANKS1B, TNFRSF21 and AGER (By similarity). Interacts with CPEB1. Interacts with ITM2B. Interacts with ITM2C. Interacts with IDE. Can form homodimers; dimerization is enhanced in the presence of Cu(2+) ions. Can form homodimers; this is promoted by heparin binding (By similarity). Amyloid-beta protein 40 interacts with S100A9 (By similarity). CTF-alpha product of APP interacts with GSAP (By similarity). Isoform APP695 interacts with SORL1 (via N-terminal ectodomain); this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (PubMed:16174740, PubMed:16407538). The C99 fragment also interacts with SORL1 (PubMed:16407538). Isoform APP751 interacts with SORL1 (PubMed:16174740). Isoform APP770 interacts with SORL1 (PubMed:16174740). Interacts with PLD3 (By similarity). Interacts with VDAC1 (PubMed:25168729). Interacts with NSG1; could regulate APP processing (PubMed:21084623). Amyloid-beta protein 42 interacts with FPR2 (By similarity). Interacts with SYT7 (PubMed:30429473). Interacts (via transmembrane region) with PSEN1; the interaction is direct (By similarity). Interacts with LRRK2 (PubMed:28720718). Interacts (via cytoplasmic domain) with KIF5B (By similarity). Interacts (via C-terminus) with APBB2/FE65L1 (via C-terminus) (PubMed:18650440). Interacts (via intracellular domain) with APBB3 (By similarity).|||Cell membrane|||Cell surface|||Chelation of metal ions, notably copper, iron and zinc, can induce histidine-bridging between amyloid-beta molecules resulting in amyloid-beta-metal aggregates. Rat and mouse amyloid-beta peptides have an arginine residue substituted for the bridging histidine residue and are thus less capable of forming amyloid aggregates. Extracellular zinc-binding increases binding of heparin to APP and inhibits collagen-binding (By similarity).|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Endoplasmic reticulum|||Endosome|||Expressed in 4 to 24 week old mice.|||Expressed in kidney.|||Expressed in several different brain regions including hippocampus, substantia nigra pars compacta and cerebellum (PubMed:8510506). Within the cerebellum, abundantly expressed in Purkinje cells (PubMed:8510506).|||Expressed in the brain with expression in cortex, cerebellum, hippocampus, olfactory bulb, neurons, astrocytes and microglia (at protein level) (PubMed:25757569, PubMed:26260791, PubMed:28720718). Expressed in the retinal lens (PubMed:25757569). Expressed at a low level in muscle cells (at protein level) (PubMed:25757569).|||Expressed in the brain, kidney and liver (PubMed:8510506). Expressed in several different brain regions including hippocampus, substantia nigra pars compacta and cerebellum (PubMed:8510506). Within the cerebellum, abundantly expressed in Purkinje cells (PubMed:8510506).|||Extracellular binding and reduction of copper, results in a corresponding oxidation of Cys-144 and Cys-158, and the formation of a disulfide bond.|||Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.|||Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibit Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o)-alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (By similarity). May be involved in copper homeostasis/oxidative stress through copper ion reduction. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV (By similarity). The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons (By similarity). Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1.|||Golgi apparatus|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||N- and O-glycosylated.|||N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).|||Nucleus|||Perikaryon|||Phosphorylation in the C-terminal on tyrosine, threonine and serine residues is neuron-specific (By similarity). Phosphorylation can affect APP processing, neuronal differentiation and interaction with other proteins (By similarity). Phosphorylated on Thr-743 in neuronal cells by Cdc5 kinase and Mapk10, in dividing cells by Cdc2 kinase in a cell-cycle dependent manner with maximal levels at the G2/M phase and, in vitro, by GSK-3-beta (By similarity). The Thr-743 phosphorylated form causes a conformational change which reduces binding of Fe65 family members (By similarity). In dopaminergic (DA) neurons, phosphorylation on Thr-743 by LRKK2 promotes the production and the nuclear translocation of the APP intracellular domain (AICD) which induces DA neuron apoptosis (PubMed:28720718). Phosphorylation on Tyr-757 is required for SHC binding (By similarity). Phosphorylated in the extracellular domain by casein kinases on both soluble and membrane-bound APP (By similarity). This phosphorylation is inhibited by heparin (By similarity).|||Proteolytically cleaved by caspases during neuronal apoptosis. Cleavage at Asp-739 by either CASP6, CASP8 or CASP9 results in the production of the neurotoxic C31 peptide and the increased production of amyloid-beta peptides.|||Proteolytically processed under normal cellular conditions (PubMed:11553691, PubMed:23931995). Cleavage either by alpha-secretase, beta-secretase or theta-secretase leads to generation and extracellular release of soluble APP peptides, S-APP-alpha and S-APP-beta, and the retention of corresponding membrane-anchored C-terminal fragments, C80, C83 and C99 (PubMed:11553691, PubMed:23931995). Subsequent processing of C80 and C83 by gamma-secretase yields P3 peptides. This is the major secretory pathway and is non-amyloidogenic. Alternatively, presenilin/nicastrin-mediated gamma-secretase processing of C99 releases the amyloid-beta proteins, amyloid-beta protein 40 and amyloid-beta protein 42, major components of amyloid plaques, and the cytotoxic C-terminal fragments, gamma-CTF(50), gamma-CTF(57) and gamma-CTF(59). PSEN1 cleavage is more efficient with C83 than with C99 as substrate (in vitro). Amyloid-beta protein 40 and Amyloid-beta protein 42 are cleaved by ACE. Many other minor amyloid-beta peptides, amyloid-beta 1-X peptides, are found in cerebral spinal fluid (CSF) including the amyloid-beta X-15 peptides, produced from the cleavage by alpha-secretase (By similarity).|||Secreted|||Sulfated on tyrosine residues.|||The C-terminal region can bind zinc ions; this favors dimerization and formation of higher oligomers.|||The GFLD subdomain binds Cu(2+) ions; this promotes homodimerization.|||The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The PID domain-containing proteins which bind APP require the YENPTY motif for full interaction. These interactions are independent of phosphorylation on the terminal tyrosine residue. The YENPXY site is also involved in clathrin-mediated endocytosis.|||The OX-2 motif shows some similarity to a region in the N-terminus of CD200/MOX2.|||The basolateral sorting signal (BaSS) is required for sorting of membrane proteins to the basolateral surface of epithelial cells.|||The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.|||The transmembrane helix undergoes a conformation change and unravels partially when bound to PSEN1, facilitating cleavage by PSEN1.|||Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP).|||Up-regulated in animals on a high-fat diet compared to a regular diet.|||Vesicle|||Widely expressed (PubMed:8510506). Expressed in several different brain regions including hippocampus, substantia nigra pars compacta and cerebellum (PubMed:8510506). Within the cerebellum, abundantly expressed in Purkinje cells (PubMed:8510506).|||clathrin-coated pit|||growth cone|||trans-Golgi network http://togogenome.org/gene/10090:Nap1l4 ^@ http://purl.uniprot.org/uniprot/A2RSB1|||http://purl.uniprot.org/uniprot/B7ZNL2|||http://purl.uniprot.org/uniprot/Q78ZA7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as histone chaperone in nucleosome assembly (PubMed:28366643). In condensing spermatids, mediates the loading of the heterodimer composed of histones H2AB1 and H2BC1/TH2B onto the nucleosomes, thereby promoting the replacement of histones to protamine in male germ cells (PubMed:28366643).|||Belongs to the nucleosome assembly protein (NAP) family.|||Cytoplasm|||Interacts with core (H2A, H2B, H3, H4) and linker (H1) histones.|||Nucleus|||Phosphorylated at the G0/G1 boundary but it is not phosphorylated in S-phase. Phosphorylated protein remains in the cytoplasm in a complex with histones during the G0/G1 transition, whereas dephosphorylation triggers its transport into the nucleus at the G1/S-boundary.|||Polyglutamylated and polyglycylated. These 2 modifications occur exclusively on glutamate residues and result in either polyglutamate or polyglycine chains on the gamma-carboxyl group. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Polyglutamylated by TTLL4. http://togogenome.org/gene/10090:Msrb3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J139|||http://purl.uniprot.org/uniprot/Q8BU85 ^@ Cofactor|||Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MsrB Met sulfoxide reductase family.|||Binds 1 zinc ion per subunit.|||Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine.|||Contains a signal peptide followed by a mitochondrial transit peptide within a single transcript. However, the protein is detected exclusively within the endoplasmic reticulum. This contasts with other species, including Homo sapiens, where the signal and transit peptides are encoded on 2 mutually exclusive exons (PubMed:15249228), and where alternative splicing leads to the synthesis of either the endoplasmic reticulum resident form or the mitochondrial form.|||Endoplasmic reticulum|||Expressed in temporal bones at 15 dpc through postnatal 30, levels decrease thereafter, but is still present in the inner ear at P180.|||Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine. While in many cases methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residues.|||Monomer.|||Widely expressed. Detected in the sensory epithelia of the organ of Corti and vestibular end organs as early as P2 up to adulthood (at protein level). In the organ of Corti, present in inner and outer hair cells and, to a lesser extent, in supporting cells (at protein level). In hair cells, distributed throughout the cell body. Barely detectable level in stereocilia. Also observed in spiral ganglion neurons, but not in the stria vascularis. In the vestibular end organs, found throughout the sensory epithelium, but more intense expression in hair cells than in supporting cells (at protein level). In vestibular hair cells, present within cell bodies and to a lesser extent in kinocilia. Barely detectable in stereocilia. http://togogenome.org/gene/10090:Tmem184a ^@ http://purl.uniprot.org/uniprot/G3X923|||http://purl.uniprot.org/uniprot/Q3UFJ6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a heparin receptor in vascular cells (By similarity). May be involved in vesicle transport in exocrine cells and Sertoli cells (PubMed:18321981, PubMed:19097053).|||Belongs to the TMEM184 family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Early endosome membrane|||Endosome|||Expressed in testis, pancreas, parotid salivary gland and mammary gland (at protein level)(PubMed:17616727, PubMed:19097053).|||Membrane|||Up-regulated in the testes from 11.5 dpc until 16.5 dpc, expression is maintained in the male Sertoli cells throughout embryonic development and into adulthood. Not expressed in the female gonad during embryonic development (PubMed:17616727, PubMed:18321981). Expressed in the granulosa cells, a few days after birth, expression is maintained in granulosa cells during folliculogenesis (PubMed:17616727, PubMed:18321981). Up-regulated during embryonic pancreatic acinar cell differentiation (PubMed:19097053).|||perinuclear region|||secretory vesicle membrane http://togogenome.org/gene/10090:Arhgap17 ^@ http://purl.uniprot.org/uniprot/Q3UIA2 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3. Interacts with NHERF1, FNBP1, TRIP10, CAPZA (CAPZA1, CAPZA2 or CAPZA3), CAPZB, CD2AP and SH3KBP1/CIN85 (By similarity).|||Cytoplasm|||Membrane|||Rho GTPase-activating protein involved in the maintenance of tight junction by regulating the activity of CDC42, thereby playing a central role in apical polarity of epithelial cells. Specifically acts as a GTPase activator for the CDC42 GTPase by converting it to an inactive GDP-bound state. The complex formed with AMOT acts by regulating the uptake of polarity proteins at tight junctions, possibly by deciding whether tight junction transmembrane proteins are recycled back to the plasma membrane or sent elsewhere. Participates in the Ca(2+)-dependent regulation of exocytosis, possibly by catalyzing GTPase activity of Rho family proteins and by inducing the reorganization of the cortical actin filaments. Acts as a GTPase activator in vitro for RAC1 (By similarity).|||The BAR domain mediates the interaction with the coiled coil domain of AMOT, leading to its recruitment to tight junctions.|||tight junction http://togogenome.org/gene/10090:C2cd3 ^@ http://purl.uniprot.org/uniprot/Q52KB6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the centrioles that acts as a positive regulator of centriole elongation (PubMed:24997988). Promotes assembly of centriolar distal appendage, a structure at the distal end of the mother centriole that acts as an anchor of the cilium, and is required for recruitment of centriolar distal appendages proteins CEP83, SCLT1, CEP89, FBF1 and CEP164. Not required for centriolar satellite integrity or RAB8 activation (PubMed:24469809). Required for primary cilium formation. Required for sonic hedgehog/SHH signaling and for proteolytic processing of GLI3 (PubMed:19004860).|||Embryonic lethality between 11 dpc and 13 dpc. Embryos show multiple defects including neural tube defects, abnormal dorsal-ventral patterning of the spinal cord, a defect in left-right axis determination and severe polydactyly (extra digits).|||Interacts with OFD1; OFD1 may act as a negative regulator of C2CD3. Associates with the BBSome complex (By similarity). Interacts with IFT88, BBS4 and PCM1.|||Ubiquitously expressed in embryos between 8.5 dpc and 10.5 dpc.|||centriole|||cilium basal body http://togogenome.org/gene/10090:Marchf8 ^@ http://purl.uniprot.org/uniprot/Q9DBD2 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasmic vesicle membrane|||E3 ubiquitin-protein ligase that plays several important roles in innate immunity and adaptive immunity (PubMed:16785530, PubMed:35503863). Mediates ubiquitination of CD86 and MHC class II proteins, such as HLA-DR alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies. Possesses a very broad antiviral activity by specifically inactivating different viral fusion proteins. Targets and ubiquitinates cytoplasmic lysine residues of viral envelope glycoproteins with single transmembrane domains leading to their lysosomal degradation. Mediates the regulation of constitutive ubiquitination and trafficking of the viral restriction factor BST2 within the endocytic pathway. Plays a role in maintenance of immune tolerance to self by promoting the turnover and proteasomal degradation of PD-L1/CD274 via ubiquitination. Catalyzes the 'Lys-63'-linked polyubiquitylation of cGAS thereby inhibiting its DNA binding ability and impairing its antiviral innate immunity (PubMed:35503863).|||Early endosome membrane|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with CD86.|||Lysosome membrane|||March8-deficient mice are less susceptible than WT mice to herpesvirus infection.|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Taok2 ^@ http://purl.uniprot.org/uniprot/Q6ZQ29 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Phosphorylated by ATM (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Contaminating sequence. Sequence of unknown origin in the N- and C-terminal parts.|||Cytoplasmic vesicle membrane|||Interacts with MAP2K3 and MAP2K6 (By similarity). Self-associates. Interacts with tubulins. Interacts with MAP3K7 and interfers with MAP3K7-binding to CHUK and thus prevents NF-kappa-B activation (By similarity). Isoform 2 interacts with PCDH8; this complex may also include CDH2 (By similarity).|||Phosphorylated on Ser-1037 by MAPK14. This phosphorylation is required PCDH8 for endocytosis (By similarity).|||Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. May affect microtubule organization and stability. May play a role in the osmotic stress-MAPK8 pathway. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14/p38 MAPK activation (By similarity).|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Tesk2 ^@ http://purl.uniprot.org/uniprot/Q8VCT9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by autophosphorylation on Ser-219.|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues. Phosphorylates cofilin at 'Ser-3'. May play an important role in spermatogenesis (By similarity).|||Nucleus http://togogenome.org/gene/10090:Adra1b ^@ http://purl.uniprot.org/uniprot/Q9DBL0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasm|||Membrane|||Nucleus membrane|||This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.|||caveola http://togogenome.org/gene/10090:Wnk4 ^@ http://purl.uniprot.org/uniprot/Q80UE6 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation requires autophosphorylation of Ser-328 and Ser-332 (By similarity). Autophosphorylation and subsequent activation is inhibited by increases in intracellular ionic strength: Cl(-) potently inhibits WNK4 kinase activity via direct binding (By similarity). Also inhibited by K(+) ions (PubMed:33439774).|||Autophosphorylated at Ser-328 and Ser-332, promoting its activation (By similarity). Phosphorylated by WNK1 and WNK3 (PubMed:17975670). Phosphorylated at Ser-572 in a MAP3K15/ASK3-dependent process in response to osmotic stress or hypotonic low-chloride stimulation (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.|||Embryonic lethality (PubMed:19633012). Hypomorphic mice do not display hypokalemia and metabolic alkalosis, but show low blood pressure and increased Na(+) and K(+) excretion under low-salt diet (PubMed:19633012). Phosphorylation of OXSR1/OSR1, STK39/SPAK and SLC12A3/NCC is significantly reduced in the hypomorphic mice (PubMed:19633012).|||Interacts with the C-terminal region of KCNJ1 (PubMed:14608358). Interacts with WNK1 and WNK3 (PubMed:17975670). Interacts with KLHL3 (By similarity).|||Locates to the distal convoluted tubule, the medullary collecting duct and the cortical collecting duct of the kidney (PubMed:11498583). Expressed in pancreatic duct (PubMed:21317537).|||Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (PubMed:12515852, PubMed:14608358, PubMed:16964266, PubMed:17488636, PubMed:17975670, PubMed:17360470, PubMed:19633012, PubMed:19240212, PubMed:21486947). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:21486947). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:17488636, PubMed:19633012, PubMed:21486947). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (PubMed:14608358, PubMed:16964266, PubMed:17975670). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (PubMed:14608358, PubMed:17488636, PubMed:17975670, PubMed:19633012, PubMed:21486947). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (PubMed:14608358, PubMed:16403833, PubMed:17673510, PubMed:21317537). Also inhbits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (PubMed:17360470). May also phosphorylate NEDD4L (By similarity).|||The RFXV motif mediates recognition with downstream kinases OXSR1/OSR1 and STK39/SPAK.|||Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation. Also ubiquitinated by the BCR(KLHL2) complex.|||Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins.|||tight junction http://togogenome.org/gene/10090:Dusp13 ^@ http://purl.uniprot.org/uniprot/Q7TNW3|||http://purl.uniprot.org/uniprot/Q9DA25|||http://purl.uniprot.org/uniprot/Q9QYJ7 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Dual specificity phosphatase that dephosphorylates MAPK8/JNK and MAPK14/p38, but not MAPK1/ERK2, in vitro (By similarity). Exhibits intrinsic phosphatase activity towards both phospho-seryl/threonyl and -tyrosyl residues, with similar specific activities in vitro (PubMed:10585869).|||Most abundantly expressed in the testis.|||Not detectable in testis in the first 3 weeks of life. The expression markedly increases at approximately the 3rd week after birth and continues to increase gradually into adulthood. http://togogenome.org/gene/10090:Vmn2r83 ^@ http://purl.uniprot.org/uniprot/E9Q0G7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpx8 ^@ http://purl.uniprot.org/uniprot/Q9D7B7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glutathione peroxidase family.|||Membrane http://togogenome.org/gene/10090:Gimap4 ^@ http://purl.uniprot.org/uniprot/D3YWB5|||http://purl.uniprot.org/uniprot/D3Z7Q4|||http://purl.uniprot.org/uniprot/Q99JY3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.|||During thymocyte development, may play a role in the regulation of apoptosis.|||Expressed in thymus (in thymocytes), spleen (in splenocytes), lymph node and lung (PubMed:16509771). Expressed in B-cells and T-cells (at protein level) (PubMed:16569770, PubMed:16509771).|||Interacts (via IQ domain) with calmodulin/CALM1 only in the absence of Ca(2+) (PubMed:16569770). Interacts with BAX, but not with other Bcl-2 family members, including BAD, BAK1, BCL2, BCL2L1/Bcl-xL and BCL2L11/BimEL (PubMed:16509771).|||No visible phenotype. T-cell development, selection and activation in vivo appear to occur normally in knockout mice.|||Phosphorylated at very low levels in resting splenocytes. Rapidly and transiently phosphorylated in response to splenocyte activation. Phosphorylation is increased in cells undergoing apoptosis.|||Up-regulated during T cell development, including upon the maturation of CD4/CD8 double-positive to CD4 single-positive thymocytes.|||cytosol http://togogenome.org/gene/10090:Zfp703 ^@ http://purl.uniprot.org/uniprot/F6M3K1|||http://purl.uniprot.org/uniprot/P0CL69 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Elbow/Noc family.|||Cytoplasm|||Expressed in mammary epithelium.|||Expressed in mammary placodes from 11.5 dpc onward and in the developing intestinal epithelium.|||Interacts with DCAF7 and PHB2 (By similarity). Interacts with TLE4; increases transcriptional repression.|||Nucleus|||Transcriptional corepressor which does not bind directly to DNA and may regulate transcription through recruitment of histone deacetylases to gene promoters. Regulates cell adhesion, migration and proliferation. May be required for segmental gene expression during hindbrain development. http://togogenome.org/gene/10090:Or6b3 ^@ http://purl.uniprot.org/uniprot/Q8VGU5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prkcsh ^@ http://purl.uniprot.org/uniprot/O08795 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum|||Expressed in kidney (at protein level).|||Heterodimer of a catalytic alpha subunit (GANAB) and a beta subunit (PRKCSH) (PubMed:9148925, PubMed:27462106). Binds glycosylated PTPRC (PubMed:9148925).|||Knockout mice exhibit early embryonic lethality by 11.5 dpc. Conditional ubiquitous or kidney-specific knockdown results in polycystic liver and kidney phenotypes, respectively.|||Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:27462106, PubMed:9148925). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (PubMed:21685914). http://togogenome.org/gene/10090:Hsd3b5 ^@ http://purl.uniprot.org/uniprot/Q61694 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Expressed in the male liver, starting in late puberty.|||Mitochondrion membrane|||Responsible for the reduction of the oxo group on the C-3 of 5alpha-androstane steroids. Catalyzes the conversion of dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Does not function as an isomerase. http://togogenome.org/gene/10090:St8sia6 ^@ http://purl.uniprot.org/uniprot/Q148N5|||http://purl.uniprot.org/uniprot/Q8K4T1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Alpha-2,8-sialyltransferase that prefers O-glycans to N-glycans or glycolipids as acceptor substrates. The minimal acceptor substrate is the NeuAc-alpha-2,3(6)-Gal sequence at the non-reducing end of their carbohydrate groups.|||Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||Highly expressed in kidney and expressed and all tissues tested.|||Membrane http://togogenome.org/gene/10090:Gjb4 ^@ http://purl.uniprot.org/uniprot/A0A654ICD1|||http://purl.uniprot.org/uniprot/Q02738|||http://purl.uniprot.org/uniprot/Q8C677 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels (By similarity). Forms heteromeric channels with GJB2 (PubMed:15692151).|||Belongs to the connexin family.|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Detected in cochlea (at protein level) (PubMed:15692151). Detected in cochlea (PubMed:15692151). Expressed in skin (PubMed:1512260).|||Detected in cochlea after 15 dpc. Detected in the spiral limbus in neoneates at 2, 8 and 10 days after birth, before the onset of hearing.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||Structural component of gap junctions (PubMed:15692151). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (By similarity). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:15692151).|||gap junction http://togogenome.org/gene/10090:Mab21l1 ^@ http://purl.uniprot.org/uniprot/O70299 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10 dpc, expressed in the temporal aspect of the retina and the anterior portion of the alar midbrain. At 10.5 dpc this retinal pattern of expression persists, with expression also beginning in the lens. Also expressed in the spinal cord, the optic cup, the presumptive lens and the genital ridge. Expressed in the dorsal midline, somites, and interdigital tissues from 9.5 dpc to 13.5 dpc.|||Belongs to the mab-21 family.|||Expressed in the adult cerebellum and eye, with lower levels in the adult forebrain.|||Expression is down-regulated by BMP2.|||Mice show eye and preputial gland defects (PubMed:12642482). Most male mice are sterile, but they can reproduce by in vitro fertilization (PubMed:12642482). Mice display calvarial ossification characterized by an unclosed calvarial region with impaired growth of fontanelle and parietal bones during postnatal development (PubMed:29156428).|||Monomer. Homodecamer; composed of 2 back to back homopentamers. The protein may exist as monomer in solution and oiligomerizes upon ligand binding.|||Nucleus|||Putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye, notochord, neural tube and other organ tissues, and for embryonic turning (PubMed:11857508, PubMed:12642482). It is unclear whether it displays nucleotidyltransferase activity in vivo (By similarity). Binds single-stranded RNA (ssRNA) (By similarity). http://togogenome.org/gene/10090:Or6k14 ^@ http://purl.uniprot.org/uniprot/E9Q7E7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm13283 ^@ http://purl.uniprot.org/uniprot/A0A087WPG5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Cog6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0L5|||http://purl.uniprot.org/uniprot/Q8R3I3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG6 family.|||Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.|||Golgi apparatus membrane|||Membrane|||Required for normal Golgi function. http://togogenome.org/gene/10090:Kdm1a ^@ http://purl.uniprot.org/uniprot/A3KG93|||http://purl.uniprot.org/uniprot/Q6ZQ88 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flavin monoamine oxidase family.|||Component of a histone demethylase complex with RCOR1 (By similarity). Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. In the complex, RCOR1 strongly enhances the demethylase activity and protects it from the proteasome while PHF21A inhibits the demethylase activity. Interacts with the androgen receptor (AR) (By similarity). Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly with GFI1 and GFI1B (PubMed:17707228). Interacts with SNAI1 (via SNAG domain) (By similarity). Interacts with INSM1 (PubMed:24227653). Interacts (via AOD/Tower domain) with JADE2 (via C-terminus) (PubMed:25018020). Interacts with ESRRB; co-occupes the core set of ESRRB targets (PubMed:26206133). Interacts with SAMD1 (via WH domain); the interaction modulates KDM1A function (PubMed:33980486). Interacts with RBPJ (By similarity). Interacts with L3MBTL3 (By similarity). Interacts with ZMYND8 (By similarity).|||Down-regulated during neural differentiation.|||Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity.|||Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation (By similarity). Demethylates and stabilizes the DNA methylase DNMT1 (By similarity). Demethylates methylated 'Lys-44' and methylated 'Lys-119' of SOX2 (By similarity). Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7.|||Nucleus|||Polyubiquitinated by JADE2; which leads to its proteasomal degradation. Deubiquitinated by USP38; preventing it from degradation by the 26S proteasome (By similarity).|||Promotes neural differentiation. Accelerated emergence of neural progenitors and mature neurons in differentiating embryonic stem cells.|||The N-terminal sequences of INSM1 and SNAI1 compete with histone H3 for the same binding site and thereby inhibit histone demethylation (in vitro).|||The SWIRM domain may act as an anchor site for a histone tail.|||Ubiquitously expressed.|||Zygotic expression first appears at the morula stage. In blastocysts, expressed in the inner cell mass and trophectodermal cells. In postimplantation embryos, expression becomes ubiquitous. http://togogenome.org/gene/10090:Kcnj12 ^@ http://purl.uniprot.org/uniprot/B1ATI1|||http://purl.uniprot.org/uniprot/P52187|||http://purl.uniprot.org/uniprot/Q9D3L6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ12 subfamily.|||Cell membrane|||Highest level in cerebellum.|||Homotetramer. Forms heteromer with KCNJ4. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking (By similarity).|||Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium.|||Membrane|||Phosphatidylinositol 4,5-bisphosphate binding to the cytoplasmic side of the channel triggers a conformation change leading to channel opening. http://togogenome.org/gene/10090:Loxl3 ^@ http://purl.uniprot.org/uniprot/Q9Z175 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the lysyl oxidase family.|||Contains 1 lysine tyrosylquinone.|||Cytoplasm|||Expressed in palate: predominantly present in the palate mesenchyme and tongue (at protein level) (PubMed:26307084). In spine, expressed in the original intervertebral disk, cartilage primordia, anterior and posterior longitudinal ligaments, meninges of spinal cord, lung and heart (PubMed:26307084). In eyes, strongly expressed in the skin of the eyelid and weakly expressed in the cornea and sclera (PubMed:26307084). In lung, predominantly expressed in the pulmonary mesenchyme (PubMed:27645581). In developing muscle, expressed at myofiber ends (at protein level) (PubMed:26954549).|||Nucleus|||Perinatal lethality, due to impaired development of the palate shelves and abnormalities in the cartilage primordia of the thoracic vertebrae (PubMed:26307084, PubMed:26954549). Cleft palates and spinal deformities are caused by the decreased collagen cross-links in the palate and spine (PubMed:26307084). In addition, mice display a reduction in the saccular space in the lungs at 18.5 dpc (PubMed:26307084, PubMed:27645581). Lungs also show reduced lung volumes and weights and deformed and smaller thoracic cavities (PubMed:27645581). Excess elastic fibers are detected, possibly due to an increased expression of Loxl4 (PubMed:27645581). Embryos show defects in the somitic boundaries, due to defects in myofibers that anchor prematurely or overshoot to adjacent somites, and lack tension (PubMed:26954549). Splenocytes show increased number of T-cells into T-helper Th17 cells and constitutive acetylation of Stat3 (PubMed:28065600).|||Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins (PubMed:26954549). Catalyzes the post-translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin (PubMed:26307084). Required for somite boundary formation by catalyzing oxidation of fibronectin (FN1), enhancing integrin signaling in myofibers and their adhesion to the myotendinous junction (MTJ) (PubMed:26954549). Acts as a regulator of inflammatory response by inhibiting differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acts by interacting with STAT3 in the nucleus and catalyzing both deacetylation and oxidation of lysine residues on STAT3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (By similarity). Also able to catalyze deacetylation of lysine residues on STAT3 (By similarity).|||The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.|||extracellular space http://togogenome.org/gene/10090:Cyp26a1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J061|||http://purl.uniprot.org/uniprot/O55127 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (PubMed:9250660, PubMed:9442090, PubMed:15911617). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (By similarity). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling (PubMed:9250660, PubMed:9442090, PubMed:15911617). Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (By similarity). Involved in the convertion of atRA to all-trans-4-oxo-RA (PubMed:15911617). Able to metabolize other RAs such as 9-cis, 13-cis and 9,13-di-cis RA (PubMed:9250660). Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (Probable). May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid (By similarity).|||Belongs to the cytochrome P450 family.|||By retinoic acid.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Cep135 ^@ http://purl.uniprot.org/uniprot/Q6P5D4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CEP135/TSGA10 family.|||Centrosomal protein involved in centriole biogenesis. Acts as a scaffolding protein during early centriole biogenesis. Required for the targeting of centriole satellite proteins to centrosomes such as of PCM1, SSX2IP and CEP290 and recruitment of WRAP73 to centrioles. Also required for centriole-centriole cohesion during interphase by acting as a platform protein for CEP250 at the centriole. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (By similarity).|||Interacts with CEP250 (By similarity). Interacts with DCTN2.|||centriole http://togogenome.org/gene/10090:Pbp2 ^@ http://purl.uniprot.org/uniprot/E9QLE5 ^@ Similarity ^@ Belongs to the phosphatidylethanolamine-binding protein family. http://togogenome.org/gene/10090:Vmn2r59 ^@ http://purl.uniprot.org/uniprot/E9PUT5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Wapl ^@ http://purl.uniprot.org/uniprot/B7ZP47|||http://purl.uniprot.org/uniprot/Q65Z40 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WAPL family.|||Chromosome|||Cytoplasm|||Deubiquitinated by USP37; leading to stabilization.|||Highly expressed in large pachytene spermatocytes of testis. Down-regulated by dioxin in testis.|||Interacts with the cohesin complex throughout the cell cycle; interacts with both chromatin-bound and soluble pools of the complex. Interacts with RAD21; the interaction is direct (By similarity). Interacts with PDS5A; the interaction is direct, cohesin-dependent and competitive with CDCA5/SORORIN (By similarity). Interacts (via FGF motifs) with PDS5B; the interaction is direct (By similarity). Interacts with a SMC1 protein (SMC1A or SMC1B) and SMC3 (By similarity).|||Nucleus|||Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin. Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair (By similarity). http://togogenome.org/gene/10090:Bard1 ^@ http://purl.uniprot.org/uniprot/O70445 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.|||Homo- and heterodimer. Heterodimer (RING-type zinc finger) with BRCA1. Heterodimer (via ANK repeats and BRCT domains) with CSTF1/CSTF-50. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts with UBXN1.|||Nucleus|||Processed during apoptosis. The homodimer is more susceptible to proteolytic cleavage than the BARD1/BRCA1 heterodimer. http://togogenome.org/gene/10090:Zfp1 ^@ http://purl.uniprot.org/uniprot/P08042 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed at peak level in day 12 embryos (PubMed:2574853). Isoform 1: Maternally contributed and highly expressed at the zygotic stage, with rapidly decreasing expression at the two cell stage remaining consistently low through to morula stage (PubMed:20624068).|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Slc50a1 ^@ http://purl.uniprot.org/uniprot/Q9CXK4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SWEET sugar transporter family.|||Cell membrane|||Expressed at high levels in lung, placenta, spleen and thymus, at intermediate levels in brain, heart, kidney and testis, and at low levels in bone marrow, liver and lymph node. Within the thymus expression is highest in non-lymphoid cells.|||Golgi apparatus membrane|||Interacts with TRPV2; the interaction probably occurs intracellularly and depends on TRPV2 N-glycosylation.|||Mediates sugar transport across membranes (By similarity). May regulate the expression of RAG1 a gene involved in V(D)J recombination.|||Up-regulated in mammary gland during lactation. http://togogenome.org/gene/10090:Slc5a4a ^@ http://purl.uniprot.org/uniprot/Q9ET37 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Does not function as sodium/D-glucose symporter (PubMed:22301059). Generates D-glucose-induced depolarization in a pH-dependent manner, with activity in acidic conditions (pH 5) but not neutral conditions (PubMed:22301059).|||Expressed in small intestine (PubMed:22301059). Expressed in kidney (PubMed:12969150).|||Not inhibited by phlorizin. http://togogenome.org/gene/10090:Catsper1 ^@ http://purl.uniprot.org/uniprot/Q91ZR5 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353, PubMed:21224844, PubMed:17478420, PubMed:19516020, PubMed:17227845, PubMed:34998468). HSPA1 may be an additional auxiliary complex member (PubMed:17478420, PubMed:19516020). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE, and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (PubMed:34998468). Interacts with Ca(v)3.3/CACNA1I, leading to suppression of T-type calcium channel activity (By similarity).|||Detected only after round spermatids are produced approximately at day 18.|||In contrast to the human ortholog, not activated by progesterone.|||Mice are normal but males are sterile. Male sterility is due to defects in sperm motility unability to fertilize intact eggs. In mice lacking Catsper1, sperm lacks CatSper2 protein, while in mice lacking CatSper1, sperm lacks CatSper1 protein, suggesting that stable expression of CatSper1 protein requires CatSper2 and vice versa.|||Testis-specific.|||Voltage-gated calcium channel that plays a central role in sperm cell hyperactivation. Controls calcium entry to mediate the hyperactivated motility, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Activated by intracellular alkalinization.|||flagellum membrane http://togogenome.org/gene/10090:Atf6 ^@ http://purl.uniprot.org/uniprot/F6VAN0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Animals have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age.|||Belongs to the bZIP family. ATF subfamily.|||During unfolded protein response, a fragment of approximately 50 kDa containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases (By similarity).|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer and heterodimer with ATF6-beta. The dimer interacts with the nuclear transcription factor Y (NF-Y) trimer through direct binding to NF-Y subunit C (NF-YC). Interacts also with the transcription factors GTF2I, YY1 and SRF.|||Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which facilitates its processing, activation and nuclear translocation (PubMed:22682248). Interacts (via lumenal domain) with THBS1 (PubMed:22682248).|||Interacts with XBP1 isoform 2; the interaction occurs in a ER stress-dependent manner. Interacts with LACC1.|||N-glycosylated. The glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR) (By similarity).|||Nucleus|||Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane. Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR).|||The basic domain functions as a nuclear localization signal.|||The basic leucine-zipper domain is sufficient for association with the NF-Y trimer and binding to ERSE.|||Transcription factor that initiates the unfolded protein response (UPR) during endoplasmic reticulum stress by activating transcription of genes involved in the UPR. Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3'). Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor. May play a role in foveal development and cone function in the retina.|||Ubiquitinated by RNF186 at Lys-139, which is required for pattern recognition receptor-induced unfolded protein response-associated outcomes. http://togogenome.org/gene/10090:Dock3 ^@ http://purl.uniprot.org/uniprot/F8VPQ1|||http://purl.uniprot.org/uniprot/Q3UHH9 ^@ Similarity ^@ Belongs to the DOCK family. http://togogenome.org/gene/10090:Jrk ^@ http://purl.uniprot.org/uniprot/Q543Z9|||http://purl.uniprot.org/uniprot/Q60976 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tigger transposable element derived protein family.|||Brain; highest in the temporal and brainstem regions.|||May bind DNA.|||Nucleus http://togogenome.org/gene/10090:Man2c1 ^@ http://purl.uniprot.org/uniprot/Q91W89 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 38 family.|||Cleaves alpha 1,2-, alpha 1,3-, and alpha 1,6-linked mannose residues from glycoproteins. Involved in the degradation of free oligosaccharides in the cytoplasm.|||Cytoplasm|||Expressed in kidney and liver (at protein level) (PubMed:24550399). Widely expressed, with highest levels in lung, ovary and testis (PubMed:16904268). Also detected at lower levels in heart, brain, liver, spleen, kidney and thymus (PubMed:16904268).|||Inhibited by 1,4-dideoxy-1,4-imino-d-mannitol (DIM) and EDTA.|||Viable and fertile with no gross defects. Loss of neutral mannosidase activity leading to accumulation of free higher-order oligosaccharides such as Man(8-9)GlcNAc(1) in many organs, particularly liver and heart. Tissues show histopathological changes with strongest defects observed in liver, small intestine, kidney and central nervous system (CNS). In liver, hepatocytes appear swollen with increased levels of glycogen and accumulation of lipid droplets. In the small intestine, enterocytes accumulate glycogen apically and also develop vacuoles in the basal cell region. In the CNS, neurons in isocortex lamina V show signs of degeneration with formation of vacuoles in basal cell regions. Vacuolation is also found in glial cells of white matter tracts. In kidney, there are signs of fibrosis along Bowman's capsule and a small number of glomeruli appear to be collapsed. http://togogenome.org/gene/10090:Zp3 ^@ http://purl.uniprot.org/uniprot/P10761 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZP domain family. ZPC subfamily.|||Cell membrane|||Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP3 is essential for sperm binding and zona matrix formation.|||Cys-320, Cys-322, Cys-323 and Cys-328 are involved in two additional disulfide bonds.|||Expressed during the 2-week growth phase of oogenesis, prior to ovulation.|||Expressed in oocytes.|||O-glycosylated; removal of O-linked glycans may play an important role in the post-fertilization block to polyspermy.|||Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers. Interacts with ZP1 and ZP2.|||Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida.|||The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.|||Zona pellucida http://togogenome.org/gene/10090:Ephb2 ^@ http://purl.uniprot.org/uniprot/P54763 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated; ligand binding stimulates autophosphorylation on tyrosine residues.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||Expressed in the epithelial dark cells of the inner ear. Expressed in the region of the proximal tubules of the kidney nephron. Expressed in myogenic progenitor cells (PubMed:27446912).|||Heterotetramer upon binding of the ligand (PubMed:11780069). The heterotetramer is composed of an ephrin dimer and a receptor dimer (PubMed:11780069). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (PubMed:9883737). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome (PubMed:21029865). Interacts with AQP1; involved in endolymph production in the inner ear (PubMed:10839360). Interacts with EFNA5 (PubMed:15107857). Interacts with SPSB1 (By similarity). Interacts with SPSB4 (PubMed:28931592). Interacts with SH2D3C (PubMed:10542222).|||Highly expressed in ventral cells of the neural tube and within axons of the peripheral nervous system during development. Expressed in the vestibulo-acoustic system and hindbrain as early as 11.5 dpc. Detected in the spinal cord at 12 dpc. Expressed in cells of the developing outer retina. Also expressed in mesenchyme adjacent to vessels. In myogenic progenitor cells, highly expressed during early development (11.5 dpc) and progressively repressed as developments proceeds (PubMed:27446912).|||Ligand binding induces cleavage by matrix metalloproteinases (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved by MMPs, producing EphB2/CTF1 which is further cleaved by the PS1/gamma-secretase producing EphB2/CTF2.|||Mice are long-lived and fertile. They display strain-specific circling behavior, are hyperactive and exhibit rapid head bobbing and twirled excessively when picked-up by the tail. This is probably due to abnormal vestibular function.|||Polyubiquitinated; ligand binding stimulates ubiquitination (PubMed:17428795, PubMed:28931592). Ubiquitinated by RNF186 at Lys-891, mainly through 'Lys-27'-linked polyubiquitin chains (By similarity).|||Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (By similarity).|||axon|||dendrite http://togogenome.org/gene/10090:Ces5a ^@ http://purl.uniprot.org/uniprot/Q6AW46 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type-B carboxylesterase/lipase family.|||Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Pramel35 ^@ http://purl.uniprot.org/uniprot/A0A0J9YU01 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Nell2 ^@ http://purl.uniprot.org/uniprot/Q61220 ^@ Caution|||Function|||Subcellular Location Annotation ^@ It is uncertain whether Met-1 or Met-4 is the initiator.|||Required for neuron survival through the modulation of MAPK pathways (By similarity). Involved in the regulation of hypothalamic GNRH secretion and the control of puberty (By similarity).|||Secreted http://togogenome.org/gene/10090:Srsf10 ^@ http://purl.uniprot.org/uniprot/Q9R0U0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the splicing factor SR family.|||Nucleus speckle|||Phosphorylated. Fully dephosphorylated in mitosis and partially dephosphorylated on heat shock.|||Splicing factor that in its dephosphorylated form acts as a general repressor of pre-mRNA splicing. Seems to interfere with the U1 snRNP 5'-splice recognition of SNRNP70. Required for splicing repression in M-phase cells and after heat shock. Also acts as a splicing factor that specifically promotes exon skipping during alternative splicing. Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (By similarity). May be involved in regulation of alternative splicing in neurons (PubMed:10583508).|||The phosphorylated but not the dephosphorylated form interacts with TRA2B/SFRS10. The dephosphorylated form interacts with SNRNP70. Interacts with FUS C-terminus. Interacts with YTHDC1, leading to inhibit RNA-binding activity of SRSF10.|||Widely expressed, with high levels in brain and testis. http://togogenome.org/gene/10090:Cers4 ^@ http://purl.uniprot.org/uniprot/Q9D6J1 ^@ Caution|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Ceramide synthase that catalyzes formation of ceramide from sphinganine and acyl-CoA substrates, with high selectivity toward long and very-long chains (C18:0-C22:0) as acyl donor.|||Endoplasmic reticulum membrane|||Phosphorylated at the C-terminus by CK2.|||Some prediction bioinformatics tools predict the presence of a homeobox domain (By similarity). However, the domain is degenerate and residues that are important for DNA-binding are absent (By similarity). Moreover, the protein localizes in the endoplasmic reticulum and not in the nucleus, strongly suggesting that it does not constitute a canonical homeobox domain (PubMed:12912983).|||The last loop motif confers selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) to behenoyl-CoA (docosanoyl-CoA; C22:0-CoA) as acyl donors.|||Ubiquitously expressed, with highest levels in skin. http://togogenome.org/gene/10090:Akt1 ^@ http://purl.uniprot.org/uniprot/P31750 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:21620960, PubMed:21432781, PubMed:26095253, PubMed:26107252, PubMed:32350463). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (PubMed:9415393). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (PubMed:11579209). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (PubMed:22057101). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (PubMed:22057101). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (By similarity). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (PubMed:10454575). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (PubMed:19778506). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) (PubMed:11282895, PubMed:18288188). AKT mediates the antiapoptotic effects of IGF-I (PubMed:11282895). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (By similarity). May be involved in the regulation of the placental development (PubMed:12783884). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53. Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility. Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation. Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (By similarity). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (By similarity). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a negative regulator of the cGAS-STING pathway by mediating phosphorylation of CGAS during mitosis, leading to its inhibition (PubMed:26440888). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (By similarity). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (By similarity).|||Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the inhibition (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.|||Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction.|||Cell membrane|||Cleavage by caspase-3/CASP3 (PubMed:12124386). Cleaved at the caspase-3 consensus site Asp-462 during apoptosis, resulting in down-regulation of the AKT signaling pathway and decreased cell survival (PubMed:12124386).|||Cytoplasm|||Expressed in trophoblast and vessel endothelial cells of the placenta and in the brain at 14.5 dpc (at protein level).|||In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.|||Interacts with and phosphorylated by PDPK1 (By similarity). Interacts with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the presence of guanine nucleotides. Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A and TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression. Interacts with MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3 and STK4. Interacts (via PH domain) with SIRT1. Interacts with SRPK2 in a phosphorylation-dependent manner. Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with RAF1 (By similarity). Interacts (via the C-terminus) with CCDC88A (via its C-terminus) and THEM4 (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding. Interacts with KCTD20 (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256). Interacts with PA2G4 (By similarity). Interacts with KIF14; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529, PubMed:20189988). Forms a complex with WDFY2 and FOXO1 (PubMed:18388859). Interacts with FAM168A (By similarity). Interacts with SYAP1 (via phosphorylated form and BSD domain); this interaction is enhanced in a mTORC2-mediated manner in response to epidermal growth factor (EGF) stimulation and activates AKT1 (PubMed:23300339). Interacts with PKHM3 (PubMed:19028694). Interacts with FKBP5/FKBP51; promoting interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1 (By similarity). Interacts with TMEM175; leading to formation of the lysoK(GF) complex (By similarity).|||Nucleus|||O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction between AKT1 and PDPK1 (By similarity). O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site (PubMed:18570920, PubMed:18288188).|||Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity (PubMed:26095253, PubMed:26107252, PubMed:32350463). Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA (By similarity). This phosphorylated form localizes to the plasma membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation (By similarity). Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1 and PRKDC (PubMed:26095253, PubMed:26107252, PubMed:32350463). Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1. Ser-473 phosphorylation is enhanced by signaling through activated FLT3 (By similarity). Ser-473 is dephosphorylated by PHLPP (By similarity). Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase (PubMed:32350463). The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase (By similarity). Ser-473 is dephosphorylated by CPPED1, leading to termination of signaling (By similarity). AIM2 acts as an inhibitor of AKT1 by inhibiting phosphorylation Ser-473: AIM2 acts both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (PubMed:26107252, PubMed:32350463).|||Show fetal growth impairment and reduced vascularization in the placenta; majority of pups died within 10 days.|||The AGC-kinase C-terminal mediates interaction with THEM4.|||Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation.|||Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation.|||Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis. http://togogenome.org/gene/10090:Ptprn2 ^@ http://purl.uniprot.org/uniprot/A3KN68|||http://purl.uniprot.org/uniprot/P80560|||http://purl.uniprot.org/uniprot/Q3UU93 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||By GHRL in brain, pancreas, and insulinoma cell lines.|||Detected in brain (PubMed:15220191, PubMed:19361477). Detected in pancreas islets (at protein level) (PubMed:8681804). Detected in pancreas and brain (PubMed:8681804, PubMed:8637868).|||Expressed in early stages of pancreatic development. First expressed in 8.5 dpc embryos in the dorsal part of the midgut endoderm and by 9.5 dpc, in the pancreatic rudiment specifically in early endocrine progenitor cells. At later stages expressed in insulin- or glucagon-producing cells. During neural development, the type 2 PTP-NP is expressed in early stages of neurogenesis, and the type 1 weakly in the later stages.|||Has no tyrosine-protein phosphatase activity at mild acidic conditions (pH 5.5). The in vivo relevance of the low PPase activity for the human protein at acidic conditions (pH 4.5) is questioned. This catalytic activity seems to be affected by the replacement of a highly conserved residue in the tyrosine-protein phosphatase domain.|||Membrane|||Mice appear healthy and normal, but display mildly decreased glucose tolerance and impaired glucose-stimulated insulin secretion (PubMed:15220191). Pancreatic islets from mice lacking both Ptprn and Ptprn2 contain decreased numbers of insulin-containing vesicles and show a further decrease in insulin secretion after glucose stimuli (PubMed:21732083). Mice lacking both Ptprn and Ptprn2 appear normal, but have lower levels of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. Likewise, they have decreased numbers of synaptic vesicles in the hippocampus and show decreased neurotransmitter release after K(+) stimulation; basal levels of neurotransmitter release are unaffected. They show increased anxiety-like behavior with strongly decreased exploratory activity and rearing. Besides, they show defects in remembering conditioned learning. With increasing age, mutant mice develop a tendency to suffer seizures and display a reduced life span; roughly half of the mutant mice are dead after 40 weeks (PubMed:19361477). The majority of female mice deficient in both Ptprn and Ptprn2 are infertile or have small litters, due to abnormalities of the estrous cycle and absence of corpora lutea. These defects are due to decreased levels of luteinizing hormone and follicle-stimulating hormone (FSH) in the pituitary and decreased levels of luteinizing hormone (LH) in the blood plasma. In contrast, male mice lacking both Ptprn and Ptprn2 display normal hormone levels and normal fertility (PubMed:16269463).|||Plays a role in vesicle-mediated secretory processes (PubMed:21732083). Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation (PubMed:21732083). Plays a role in insulin secretion in response to glucose stimuli (PubMed:15220191, PubMed:16418280, PubMed:21732083). Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (PubMed:16269463). Required to maintain normal levels of renin expression and renin release (PubMed:19019914). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (PubMed:12364328). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate (By similarity). Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolyzation of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (By similarity).|||Self-associates. Interacts (via cytoplasmic domain) with PTPRN (via cytoplasmic domain) (PubMed:12364328). Interacts (precursor form) with CPE (PubMed:21210912). Interacts with HAP1 isoform A (PubMed:21544547). Interacts with AP2A1 or AP2A2 and AP1G1; indicative for an association with adaptor protein complex 2 (AP-2) and adaptor protein complex 1 (AP-1) (PubMed:16262730). Interacts with AP2M1; indicative for an association with adaptor protein complex 2 (AP-2). Interacts with MYO5A (By similarity).|||Subject to proteolytic cleavage at multiple sites during maturation of secretory granules. In the brain at least IA-2beta71, IA-2beta64 and IA-2beta60 have been detected, in the pancreas and a pancreatic beta cell line only IA-2beta60 has been detected.|||The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane.|||The tyrosine-based internalization signal is proposed to function in clathrin-mediated endocytosis and recycling.|||secretory vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Atxn3 ^@ http://purl.uniprot.org/uniprot/E9Q717|||http://purl.uniprot.org/uniprot/Q546X9|||http://purl.uniprot.org/uniprot/Q5M8S1|||http://purl.uniprot.org/uniprot/Q810M8|||http://purl.uniprot.org/uniprot/Q9CVD2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (By similarity). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (By similarity). Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (PubMed:21855799). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (By similarity). Acts as a negative regulator of mTORC1 signaling in response to amino acid deprivation by mediating deubiquitination of RHEB, thereby promoting RHEB inactivation by the TSC-TBC complex (By similarity). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (PubMed:28445460).|||Interacts with STUB1/CHIP (when monoubiquitinated) (PubMed:21855799). Interacts with DNA repair proteins RAD23A and RAD23B (By similarity). Interacts with BECN1 (via its poly-Gln domain) (PubMed:28445460). Interacts with PRKN, UBR2, VCP and tubulin (By similarity).|||Lysosome membrane|||Monoubiquitinated by UBE2W, possibly leading to activate the deubiquitinating enzyme activity (By similarity).|||Nucleus|||Nucleus matrix|||The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to limit the length of ubiquitin chains (PubMed:21855799). http://togogenome.org/gene/10090:Pdzd11 ^@ http://purl.uniprot.org/uniprot/Q9CZG9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts with ATP2B1, ATP2B2, ATP2B3, ATP2B4 and ATP7A (By similarity). Interacts with PLEKHA7 (via WW domains) at zonula adherens; this interaction is essential for the interaction between PLEKHA7 and the ADAM10-binding protein TSPAN33 (PubMed:30463011). Interacts with SLC5A6 (By similarity).|||Mediates docking of ADAM10 to zonula adherens by interacting with PLEKHA7 which is required for PLEKHA7 to interact with the ADAM10-binding protein TSPAN33.|||adherens junction http://togogenome.org/gene/10090:Smco4 ^@ http://purl.uniprot.org/uniprot/Q9JIS3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMCO4 family.|||Membrane http://togogenome.org/gene/10090:C1qbp ^@ http://purl.uniprot.org/uniprot/Q8R5L1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MAM33 family.|||Cell membrane http://togogenome.org/gene/10090:Slc35d2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J181|||http://purl.uniprot.org/uniprot/A0A1Y7VL74|||http://purl.uniprot.org/uniprot/Q762D5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPT transporter family. SLC35D subfamily.|||Golgi apparatus membrane|||Membrane|||Nucleotide sugar antiporter transporting UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-glucose (UDP-Glc) from the cytosol into the lumen of the Golgi in exchange of UMP. By supplying UDP-N-acetylglucosamine, a donor substrate to heparan sulfate synthases, probably takes part in the synthesis of these glycoconjugates. http://togogenome.org/gene/10090:Mtif2 ^@ http://purl.uniprot.org/uniprot/Q91YJ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.|||Mitochondrion|||Monomer.|||One of the essential components for the initiation of protein synthesis. Protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the 30S ribosomal subunits. Also involved in the hydrolysis of GTP during the formation of the 70S ribosomal complex (By similarity). http://togogenome.org/gene/10090:Pdgfb ^@ http://purl.uniprot.org/uniprot/A0A0R4IZW4|||http://purl.uniprot.org/uniprot/P31240 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiparallel homodimer; disulfide-linked. Antiparallel heterodimer with PDGFA; disulfide-linked. The PDGFB homodimer interacts with PDGFRA and PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts with XLKD1 (By similarity). Interacts with LRP1 (By similarity). Interacts with SORL1 (via the N-terminal ectodomain) (By similarity).|||Belongs to the PDGF/VEGF growth factor family.|||Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal proliferation and recruitment of pericytes and vascular smooth muscle cells in the central nervous system, skin, lung, heart and placenta. Required for normal blood vessel development, and for normal development of kidney glomeruli. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFA.|||Localized to vascular smooth muscle cells. Also weakly expressed by cortical interstitial cells but absent in tubules. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, an increased expression in interstitial cells and in some tubules observed after day 4.|||Perinatal lethality, due to severe hemorrhages shortly before birth. Kidney glomerular tufts do not form, apparently because of absence of mesangial cells. The heart and some large arteries are dilated in late-stage embryos. Mice lack microvascular pericytes, which normally form part of the capillary wall, and develop numerous capillary microaneurysms, leading to hemorrhages. Mice display erythroblastosis, macrocytic anemia, and thrombocytopenia.|||Secreted http://togogenome.org/gene/10090:Sertad3 ^@ http://purl.uniprot.org/uniprot/Q9ERC3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Antiviral interferon-stimulated protein that plays a role in innate immunity and in the suppression of viruses through different mechanisms (By similarity). Plays a role in the late phase response of TLR-induced immune effector expression (PubMed:28750197). Strong transcriptional coactivator (By similarity).|||Interacts with RPA2.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Rgs17 ^@ http://purl.uniprot.org/uniprot/Q9QZB0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in brain (at protein level) (PubMed:15827571, PubMed:16900103). Highly expressed in the hypothalamus, periaqueductal gray matter, and pons-medulla. Lower levels in the thalamus, cortex and spinal cord. Weak expression in the striatum and cerebellum.|||Interacts with GNAI1 and GNAQ (By similarity). Interacts with GNAZ and GNAI2 (PubMed:15827571, PubMed:16900103). Interacts with OPRM1 (PubMed:15827571). Forms a complex with mu-opioid receptors and G(alpha)z/i2 subunits, including GNAZ and GNAI2; the formation of this complex results in mu-opioid receptor desensitization (PubMed:15827571). Interacts with HINT1 (PubMed:31088288).|||Membrane|||N- and O-glycosylated in synapsomal membranes.|||Nucleus|||Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2 (By similarity). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Binds selectively to GNAZ and GNAI2 subunits, accelerates their GTPase activity and regulates their signaling activities. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins.|||Serine phosphorylated in synapsomal membranes.|||Sumoylated with SUMO1 and SUM02 in synaptosomes. The sumoylated forms act as a scaffold for sequestering mu-opioid receptor-activated G(alpha) subunits (PubMed:16900103). Desumoylated by HINT1 (PubMed:31088288).|||synaptosome http://togogenome.org/gene/10090:Bicral ^@ http://purl.uniprot.org/uniprot/Q8CHH5 ^@ Function|||Subunit ^@ Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, the core BAF subunits, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A. http://togogenome.org/gene/10090:Gykl1 ^@ http://purl.uniprot.org/uniprot/Q8C635 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FGGY kinase family.|||Cytoplasm http://togogenome.org/gene/10090:Oxct2b ^@ http://purl.uniprot.org/uniprot/A0A0R4J198|||http://purl.uniprot.org/uniprot/Q9ESL0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 3-oxoacid CoA-transferase family.|||Homodimer.|||Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity). Probably play and important roles in the energy metabolism of spermatozoa.|||Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.|||Mitochondrion|||Testis specific. Expressed in late spermatids. Accumulates during spermiogenesis. Also detected in the midpiece of spermatozoa. http://togogenome.org/gene/10090:Arhgdia ^@ http://purl.uniprot.org/uniprot/Q99PT1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Rho GDI family.|||Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1.|||Cytoplasm|||From 1 week to 12 weeks of age, progressive deterioration from mild to massive albuminuria as consequence of renal abnormalities. In kidney, severe podocyte damage, glomerular lesions with focal and segmental sclerosis, along with prominent intratubular casts and luminal dilatation. Tubular epithelial cells show degenerative changes with basement membrane thickening. Increase of apoptotic cells in kidney glomeruli and tubulointerstitium.|||In kidney glomerulus, expressed in podocytes and mesangial cells.|||Monomer (PubMed:22628549). Interacts with FER (By similarity). Interacts with PLXNB3 (PubMed:20696765). Forms a heterodimer with RAC1 (PubMed:23434736). Interacts with RHOA, the affinity is increased by three orders of magnitude when RHOA is prenylated (PubMed:23434736). Interacts with PSMD10; the interaction increases ARHGDIA association with RHOA, leading to ARHGDIA-mediated inactivation of RHOA and ROCK and prolonged AKT activation (By similarity). Interacts with KANK2; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (By similarity). Interacts with RHOC (By similarity). Interacts with CDC42 (PubMed:23434736). Interacts with NGFR (via death domain); NGFR binding decreases the affinity for RHOA (By similarity). http://togogenome.org/gene/10090:Cyp4a12b ^@ http://purl.uniprot.org/uniprot/A2A974|||http://purl.uniprot.org/uniprot/B0G0Y1|||http://purl.uniprot.org/uniprot/B0G0Y2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of fatty acids and their oxygenated derivatives (oxylipins) (PubMed:17112342). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:17112342). Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of saturated and unsaturated fatty acids (PubMed:17112342). May act as a major omega-hydroxylase for dodecanoic (lauric) acid in kidney (PubMed:17112342). Participates in omega-hydroxylation of (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to 20-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:17112342). Acts as an omega-hydroxylase and epoxidase toward (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoc acid (EPA). Catalyzes the epoxidation of the last double bond of EPA with no preferred stereoselectivity, producing both (R,S) and (S,R) stereoisomers (PubMed:17112342). Can also catalyze the omega-1 and omega-2 oxidation of fatty acids with lower efficiency (PubMed:17112342).|||Activated by cytochrome b5. The Vmax almost doubles in the presence of cytochrome b5.|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in lung, but almost undetectable in the kidneys of five different strains.|||Microsome membrane http://togogenome.org/gene/10090:Trnt1 ^@ http://purl.uniprot.org/uniprot/Q8K1J6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family.|||Cytoplasm|||Mitochondrion|||Monomer, and homodimer.|||Nucleotidyltransferase that catalyzes the addition and repair of the essential 3'-terminal CCA sequence in tRNAs, which is necessary for the attachment of amino acids to the 3' terminus of tRNA molecules, using CTP and ATP as substrates. tRNA 3'-terminal CCA addition is required both for tRNA processing and repair. Promotes tRNA repair and recycling downstream of the ribosome-associated quality control (RQC) pathway by mediating addition of the tRNA 3'-terminal CCA following cleavage by ANKZF1 and repair by ELAC1. Also involved in tRNA surveillance by mediating tandem CCA addition to generate a CCACCA at the 3' terminus of unstable tRNAs and tRNA-like transcripts. While stable tRNAs receive only 3'-terminal CCA, unstable tRNAs beginning with GG are marked with CCACCA and rapidly degraded. The structural flexibility of RNA controls the choice between CCA versus CCACCA addition: following the first CCA addition cycle, nucleotide-binding to the active site triggers a clockwise screw motion, producing torque on the RNA. This ejects stable RNAs, whereas unstable RNAs are refolded while bound to the enzyme and subjected to a second CCA catalytic cycle.|||Nucleus http://togogenome.org/gene/10090:Tcl1b5 ^@ http://purl.uniprot.org/uniprot/P56845|||http://purl.uniprot.org/uniprot/Q3UT92 ^@ Similarity ^@ Belongs to the TCL1 family. http://togogenome.org/gene/10090:Abcd2 ^@ http://purl.uniprot.org/uniprot/Q61285 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (By similarity). Like ABCD1 seems to have fatty acyl-CoA thioesterase (ACOT) and ATPase activities, according to this model, VLCFA-CoA as free VLCFA is transpoted in an ATP-dependent manner into peroxisomes after the hydrolysis of VLCFA-CoA mediated by the ACOT activity of ABCD2 (By similarity). Shows overlapping substrate specificities with ABCD1 toward saturated fatty acids (FA) and monounsaturated FA (MUFA) but has a distinct substrate preference for shorter VLCFA (C22:0) and polyunsaturated fatty acid (PUFA) such as C22:6-CoA and C24:6-CoA (in vitro) (By similarity). Thus, may play a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation (PubMed:18854420, PubMed:16223892).|||Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.|||Deficient mice exhibit a late-onset cerebellar and sensory ataxia, loss of Purkinje cells, dorsal root ganglia cell degeneration, axonal degeneration in the spinal cord, and an accumulation of very long chain fatty acids (C26:0 and C24:0) in dorsal root ganglia cells, and reduced levels of C22:6omega3 in primary neurons.|||Homodimers. Homotetramers. The minimal functional unit is a homodimer but the major oligomeric form in peroxisomal membrane is a homotetramer. Forms heterotramers with ABCD1. Forms heterodimers with ABCD3. In addition to tetramers, some larger molecular assemblies are also found but represented only a minor fraction. Interacts with PEX19.|||Peroxisome membrane|||Strongly expressed in brain and adrenals, and weakly expressed in liver. http://togogenome.org/gene/10090:Trim43c ^@ http://purl.uniprot.org/uniprot/P86449 ^@ Developmental Stage|||Similarity ^@ Belongs to the TRIM/RBCC family.|||Expression is restricted to preimplantation embryos and peaks at the 8-cell to morula stage. http://togogenome.org/gene/10090:Pus3 ^@ http://purl.uniprot.org/uniprot/Q9JI38 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tRNA pseudouridine synthase TruA family.|||Formation of pseudouridine at position 39 in the anticodon stem and loop of transfer RNAs. Also acts on position 38, but much less efficiently.|||Nucleus http://togogenome.org/gene/10090:Rcbtb1 ^@ http://purl.uniprot.org/uniprot/Q6NXM2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ In the retina, mainly expressed in the inner retina with strong signals reaching up to the outer plexiform layer (at protein level).|||May be involved in cell cycle regulation by chromatin remodeling.|||Nucleus http://togogenome.org/gene/10090:Nmnat2 ^@ http://purl.uniprot.org/uniprot/Q5HZI3|||http://purl.uniprot.org/uniprot/Q8BNJ3 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic NMN adenylyltransferase family.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Degraded in response to injured neurite (PubMed:20126265, PubMed:23665224, PubMed:23610559). Degradation is caused by polyubiquitination by MYCBP2 after recognition by FBXO45 (PubMed:23665224, PubMed:23610559).|||Divalent metal cations. Mg(2+) confers the highest activity.|||Expressed predominantly in the brain and nervous system.|||Golgi apparatus membrane|||Inhibited by P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate (Np3AD) and P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate (Np4AD).|||Monomer.|||Nicotinamide/nicotinate-nucleotide adenylyltransferase that acts as an axon maintenance factor (PubMed:20126265, PubMed:23082226). Axon survival factor required for the maintenance of healthy axons: acts by delaying Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons (PubMed:20126265, PubMed:23082226, PubMed:25818290). Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (By similarity). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate but with a lower efficiency. Cannot use triazofurin monophosphate (TrMP) as substrate (By similarity). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity prefers NAD(+), NADH and NaAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively (By similarity). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (By similarity). Also acts as an activator of ADP-ribosylation by supporting the catalytic activity of PARP16 and promoting mono-ADP-ribosylation of ribosomes by PARP16 (By similarity).|||Palmitoylated; palmitoylation is required for membrane association.|||Perinatal lethality (PubMed:23082226). Mice show a greatly distended bladder, underdeveloped diaphragm and a reduction in total skeletal muscle mass (PubMed:23082226). Defects are caused by defects in innervation of major organs and tissues (PubMed:23082226). Mice lacking both Sarm1 and Nmnat2 are viable and survive: Sarm1 deficiency corrects axon outgrowth in mice lacking Nmnat2, independently of NMNAT metabolites, preventing perinatal lethality (PubMed:25818290).|||axon http://togogenome.org/gene/10090:Pcolce2 ^@ http://purl.uniprot.org/uniprot/Q8R4W6 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds to the C-terminal propeptide of types I and II procollagens and may enhance the cleavage of that propeptide by BMP1.|||Expressed at all stages of development, with expression level decreasing from 7 to 11 dpc and more abundant levels of expression at 15 and 17 dpc. First detectable at relatively low level at 10.5 dpc in the area of the third and fourth branchial arches. At 13.5 dpc easily discernible expression seems primarily confined to the cartilage primordia of future bones. At 15.5 dpc expressed at the highest levels in skeletal elements in the interior non-ossified regions of cartilaginous structures and excluded from regions of ossification.|||Interacts with heparin with high affinity, and type I or II collagen.|||O-glycosylated; contains sialic acid.|||Secreted http://togogenome.org/gene/10090:Rpp14 ^@ http://purl.uniprot.org/uniprot/Q9CQH8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic/archaeal RNase P protein component 2 family.|||Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.|||RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA.|||nucleolus http://togogenome.org/gene/10090:Prl8a2 ^@ http://purl.uniprot.org/uniprot/O35258|||http://purl.uniprot.org/uniprot/O54832 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Or10aa3 ^@ http://purl.uniprot.org/uniprot/E9Q8M2|||http://purl.uniprot.org/uniprot/Q3KPC8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Frzb ^@ http://purl.uniprot.org/uniprot/P97401 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the secreted frizzled-related protein (sFRP) family.|||Expressed in kidney, brain, testis. Weak expression in spleen and heart.|||In early gastrulation, expressed in all three germ layers. In later embryogenesis, expressed in a range of tissues including the central and peripheral nervous systems and the nephogenic mesenchyme.|||Interacts with MYOC.|||Secreted|||Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP3/FRZB appears to be involved in limb skeletogenesis. Antagonist of Wnt8 signaling. Regulates chondrocyte maturation and long bone development (By similarity).|||The FZ domain is involved in binding with Wnt ligands. http://togogenome.org/gene/10090:Mrps35 ^@ http://purl.uniprot.org/uniprot/Q8BJZ4 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS35 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Rcan3 ^@ http://purl.uniprot.org/uniprot/Q9JKK0 ^@ Function|||Similarity|||Subunit ^@ Belongs to the RCAN family.|||Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development (By similarity).|||Interacts with protein phosphatase PPP3CA/calcineurin A. http://togogenome.org/gene/10090:Or10k2 ^@ http://purl.uniprot.org/uniprot/E9Q848 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sowahd ^@ http://purl.uniprot.org/uniprot/Q8BY98 ^@ Similarity ^@ Belongs to the SOWAH family. http://togogenome.org/gene/10090:Kcnmb3 ^@ http://purl.uniprot.org/uniprot/E9Q7U0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KCNMB (TC 8.A.14.1) family.|||Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB per KCNMA1 tetramer.|||Membrane|||N-glycosylated.|||Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. http://togogenome.org/gene/10090:Prr23a3 ^@ http://purl.uniprot.org/uniprot/Q9CWP9 ^@ Similarity ^@ Belongs to the PRR23 family. http://togogenome.org/gene/10090:Vmn1r76 ^@ http://purl.uniprot.org/uniprot/F8VQ63 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aipl1 ^@ http://purl.uniprot.org/uniprot/Q924K1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with NUB1.|||May be important in protein trafficking and/or protein folding and stabilization.|||Nucleus http://togogenome.org/gene/10090:Idi2 ^@ http://purl.uniprot.org/uniprot/Q8BFZ6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IPP isomerase type 1 family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to its highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).|||Peroxisome http://togogenome.org/gene/10090:Chaf1a ^@ http://purl.uniprot.org/uniprot/Q9QWF0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CHAF1A family.|||Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain.|||Core component of the CAF-1 complex, a complex that is thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer. It may play a role in heterochromatin maintenance in proliferating cells by bringing newly synthesized cbx proteins to heterochromatic DNA replication foci.|||Homodimer. Part of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A. CHAF1A binds directly to CHAF1B. Only minor amounts of RBBP4 are complexed with CHAF1A and CHAF1B in G1 phase. CHAF1A binds directly to PCNA and to CBX1. Interacts with MBD1. Interacts directly with CBX5 via the PxVxL motif. Interacts with CBX5. Interacts with histones H3.1, H3.2 and H3.1t (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or10j3b ^@ http://purl.uniprot.org/uniprot/Q8VGE1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Il13ra1 ^@ http://purl.uniprot.org/uniprot/O09030|||http://purl.uniprot.org/uniprot/Q8BNM4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 5 subfamily.|||Binds with low affinity to interleukin-13 (IL13). Together with IL4RA can form a functional receptor for IL13. Also serves as an alternate accessory protein to the common cytokine receptor gamma chain for interleukin-4 (IL4) signaling, but cannot replace the function of IL2RG in allowing enhanced interleukin-2 (IL2) binding activity (By similarity).|||Interleukin-13 receptor is a complex of IL4R, IL13RA1, and possibly other components. Interacts with TRAF3IP1 (By similarity). Interacts with IL4 (By similarity).|||Membrane|||Spleen, liver, thymus, heart, lung, kidney, testis, stomach, brain, skin, and colon; but not skeletal muscle.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Cenpi ^@ http://purl.uniprot.org/uniprot/Q3TTB0|||http://purl.uniprot.org/uniprot/Q8K1K4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-I/CTF3 family.|||Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Required for the localization of CENPF, MAD1L1 and MAD2 (MAD2L1 or MAD2L2) to kinetochores. Involved in the response of gonadal tissues to follicle-stimulating hormone (By similarity).|||Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Interacts with SENP6 (By similarity).|||Nucleus|||Sumoylated. Sumoylated form can be polyubiquitinated by RNF4, leading to its degradation. Desumoylation by SENP6 prevents its degradation (By similarity).|||centromere http://togogenome.org/gene/10090:Creb3l3 ^@ http://purl.uniprot.org/uniprot/Q91XE9 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. ATF subfamily.|||Binds DNA as a dimer. May form homodimers (By similarity). Interacts with ATF6 (By similarity). Interacts with SYNV1/HRD1; this interaction leads to CREB3L3 ubiquitination and proteasomal degradation (PubMed:30389664).|||By IL6. Pro-inflammatory cytokines and lipopolysaccharide activate the UPR and induce cleavage of CREBH in the liver (PubMed:16469704). Down-regulated in the liver during fasting-refeeding. This down-regulation may occur at the postranscriptional level and may be mediated by SYNV1/HRD1, which induces CREB3L3 ubiquitination and proteasomal degradation (PubMed:30389664).|||Endoplasmic reticulum membrane|||Expressed in adult liver (at protein level) and small intestine.|||Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (By similarity).|||Knockout mice display decreased triglyceride clearance from plasma resulting in hypertriglyceridemia.|||N-glycosylation is required for optimal proteolytic activation.|||Nucleus|||Transcription factor that may act during endoplasmic reticulum (ER) stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. Binds to the cAMP response element (CRE). Activates transcription through box-B element (By similarity). Activates transcription through CRE. May function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression. Regulates FGF21 transcription (PubMed:30389664). Plays a crucial role in the regulation of triglyceride metabolism and is required for the maintenance of normal plasma triglyceride concentrations (PubMed:21666694).|||Ubiquitinated at Lys-290 by SYNV1/HRD1 via 'Lys-27'-linked ubiquitin. http://togogenome.org/gene/10090:Obox5 ^@ http://purl.uniprot.org/uniprot/G3X9P6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Ogn ^@ http://purl.uniprot.org/uniprot/Q543C5|||http://purl.uniprot.org/uniprot/Q62000 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.|||Contains keratan sulfate.|||Induces bone formation in conjunction with TGF-beta-1 or TGF-beta-2.|||extracellular matrix http://togogenome.org/gene/10090:Strap ^@ http://purl.uniprot.org/uniprot/Q9Z1Z2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat STRAP family.|||Cytoplasm|||Nucleus|||Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG. Interacts directly with GEMIN6 and GEMIN7. Associates with the SMN complex in the cytoplasm but not in the nucleus. Also interacts with CSDE1/UNR and MAWBP. Interacts with PDPK1. Interacts with TRIM48.|||The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. STRAP plays a role in the cellular distribution of the SMN complex. Negatively regulates TGF-beta signaling but positively regulates the PDPK1 kinase activity by enhancing its autophosphorylation and by significantly reducing the association of PDPK1 with 14-3-3 protein (By similarity). http://togogenome.org/gene/10090:Rpl29 ^@ http://purl.uniprot.org/uniprot/P47915|||http://purl.uniprot.org/uniprot/Q5M8M8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL29 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Or6c3b ^@ http://purl.uniprot.org/uniprot/Q8VFI3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fut8 ^@ http://purl.uniprot.org/uniprot/B2X2D7|||http://purl.uniprot.org/uniprot/B2X2D8|||http://purl.uniprot.org/uniprot/Q9WTS2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 23 family.|||Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.|||Golgi stack membrane|||Tyrosine phosphorylated by PKDCC/VLK. http://togogenome.org/gene/10090:Tbata ^@ http://purl.uniprot.org/uniprot/Q7TSD4 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBATA family.|||Expressed in the subcapsular region of the thymus and lymph node (at protein level). Highly expressed in thymic cortical stromal cells and testis. Lower levels found in brain cortex, hippocampus, kidney, cerebellum, skeletal muscle, epididymis and ovary. No expression detected in other lymphoid organs including bone marrow and spleen. Isoform 1 and isoform 2 are expressed predominantly in testis. Isoform 3, isoform 4 and isoform 5 are expressed predominantly in thymus although isoform 3 is also expressed in testis. In the CNS, highly expressed in restricted areas, the cerebellum and hippocampus.|||In testis, isoform 1 and isoform 2 are expressed only in the adult from postnatal week 7. Expression is detected in pachytene spermatocytes, increases greatly in round spermatids and is very strong in round/elongating and elongating spermatids. Expression is reduced in condensed spermatids and persists in spermatozoa. Isoform 3 is specifically expressed in round spermatids and is greatly reduced in spermatids under maturation (at protein level). Isoform 7 is detected in the embryo from day 10 while isoform 7 is not detected until day 12. In brain, predominantly expressed by granule cells during cerebellar development. Isoform 1 and isoform 3 are differentially expressed during cerebellar development.|||Interacts with KIF17. Interacts with UBA3.|||Isoform 1 and isoform 2 may play a role in spermatid differentiation. Isoform 1 and isoform 2 regulate thymus function by modulating stromal cell proliferation via interference with the NEDD8 pathway.|||Nucleus|||Up-regulated in aged mice (4 months of age or older).|||cytosol http://togogenome.org/gene/10090:Sorl1 ^@ http://purl.uniprot.org/uniprot/O88307 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ After maturation cleavage, interacts (via N-terminus) with its own propeptide; this interaction prevents interaction with other ligands, including CRLF1, GDNF, GFRA1, IL6 and IL6R (By similarity). Interacts (via N-terminal ectodomain) with APP, forming a 1:1 stoichiometric complex, including with isoforms APP695, APP751 and APP770; this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides (PubMed:16174740, PubMed:16407538). Also interacts with APP C-terminal fragment C99 and with Abeta40 (By similarity). Interacts with beta-secretase BACE1/BACE; this interaction may affect BACE1-binding to APP and hence reduce BACE1-dependent APP cleavage (PubMed:16407538). Interacts with LRPAP1/RAP (By similarity). Interacts (via C-terminal cytosolic domain) with GGA1 and GGA2 (via N-terminal VHS domain) (By similarity). Interacts with PACS1 (By similarity). May interact (via the N-terminal ectodomain) with the morphogenetic neuropeptide, also called head activator or HA; this interaction is impaired in the presence of propeptide (By similarity). Interacts with neurotensin/NTS (By similarity). Interacts (via the N-terminal ectodomain) with PDGFB homodimer (By similarity). Interacts (via N-terminal ectodomain) with the uPA receptor PLAUR (By similarity). Interacts with uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each other, leading to endocytosis (By similarity). Also interacts with PAI1/SERPINE1 in complex with tPA/PLAT. Interacts (via C-terminus) with AP-1 and AP-2 complexes (By similarity). Interacts with BMPR1A and BMPR1B (PubMed:26584636). Interacts with lipoprotein lipase LPL; this interaction is optimal in slightly acidic conditions (By similarity). Interacts (via N-terminal ectodomain) with GDNF (via propeptide) and GDNF receptor alpha-1/GFRA1, either individually or in complex with each other (By similarity). The interaction with GDNF occurs mostly intracellularly (By similarity). Also interacts with other GDNF receptor alpha family members, including GFRA2, GFRA3 and GFRA4 (By similarity). Interacts with the insulin receptor INSR; this interaction strongly increases the surface exposure of INSR (PubMed:27322061). Interacts (via cytosolic C-terminus) with STK39/SPAK (By similarity). Interacts (via N-terminal ectodomain) with the heterodimeric complex CRLF1-CLC; within this complex, the interaction is mediated predominantly by the CRLF1 moiety (By similarity). Interacts with CNTFR, as well as with the tripartite signaling complex formed by CRLF1, CLC and CNTFR (By similarity). Interacts (via N-terminal ectodomain) with IL6; this interaction leads to IL6 internalization and lysosomal degradation. Binding of SOLRL1 secreted N-terminal ectodomain to IL6 may increase IL6 trans signaling (By similarity). Interacts with secreted IL6R; this interaction leads to IL6R internalization (PubMed:28265003). Also interacts with transmembrane IL6R; this interaction does not affect subcellular location. Interacts with APOE (By similarity). Interacts with apolipoprotein E-rich beta-VLDL (By similarity). Interacts with APOA5; this interaction leads to APOA5 internalization and is abolished by heparin. Interaction with APOA5 results in enhanced binding to chylomicrons. Interacts with ROCK2 (By similarity). Interacts (via cytosolic C-terminus) with PPP3CB/calcineurin A beta (PubMed:25967121). Interacts with NTRK2/TRKB; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (PubMed:23977241). Interacts (via cytosolic C-terminus) with HSPA12A in an ADP-dependent manner; this interaction affects SORL1 internalization and subcellular localization (By similarity). Interacts (via N-terminal ectodomain) with ERBB2/HER2 (By similarity).|||Belongs to the VPS10-related sortilin family. SORL1 subfamily.|||Cell membrane|||Early endosome membrane|||Endoplasmic reticulum membrane|||Endosome membrane|||Expression starts at 6.5 dpc (PubMed:9726247, PubMed:9510025). At 7.5 dpc, expressed over the entire embryo, with highest levels in the amnion. Up to 8.5 dpc, expression further increases and becomes more restricted to the foregut and the amnion. At 9.5 dpc, expression increases in the somites, as well as the developing gut, and is observed over the facial-cranial mesenchyme and the branchial arches. At 10.5 dpc, expression in the mesenchyme and the somites reaches its maximal intensity. At this stage, highest expression level is observed over the ventral part of the neural tube, in the marginal zone, and extends throughout the hindbrain. Also expressed in motor neurons of the spinal cord. With ongoing development, the brain becomes the main site of expression. At 11.5 dpc, expressed in the telencephalon, being restricted to the lateral aspects of the developing cerebral cortex, with highest levels in the outer layer of the neuronal tissue of the developing cerebral cortex. Also observed in the myelencephalon and in a thin cell layer in the rhombic lip of the metencephalon. At 12.5 dpc, expression begins in the mesencephalon and the diencephalon. Up to 14.5 dpc, expression levels in the developing cerebral cortex become more even and spread to more dorsal and caudal locations. At 14.5 dpc, decreased expression in the metencephalon and the myelencephalon. At 16.5 dpc, expressed over the entire cortical area, although at a slightly lower intensity. Expressed in the hypothalamus. At this stage, expression begins in the peripheral nervous system, including in the trigeminal ganglion, the dorsal root ganglia, the cochlear-vestibular ganglia and the sympathetic ganglia chain, but at lower levels compared to the central nervous system. Expressed over the mitral cell layer of the olfactory bulb and between the 2 outer walls of the gut. The overall expression levels in the cortex decrease until birth. At 18.5 dpc, the outer aspects of the cortical plate shows lower expression levels than the subventricular zone. At 18.5 dpc, expressed in the retina and the geniculate nucleus of the thalamus; this expression increases towards P0. At P0, expression levels are higher in the outer aspects of the cortical plate than in the subventricular zone (PubMed:9510025). 1 week after birth, abundantly expressed in the cerebrum, then levels decrease and become nearly undetectable at 4 weeks. Expression increases again and reaches moderate levels at 12 weeks. In the cerebellum, expressed at high levels during the first 2 weeks. Expression decreases at 4 and 8 weeks, and then increases again at 12 weeks (PubMed:9726247). Expressed in many organs outside the nervous system during organogenesis, such as the primitive gut where expression is detected already at 8.5 dpc. Other SORL1-expressing organs include the genital bud, the mesenchymal tissue, the developing skeletal muscles, the myocardium, the pituitary, the pineal, the thyroid and the Haderian glands, as well as the developing serous glands of the nasal cavity, the salivary and the submandibular glands, the pancreas, the epithelia of the stomach, the tubules of the kidney, the tooth germ, the cochlea, the nasal cavity, the trachea, the lung, the bladder and urethra, the intestine and the rectum (PubMed:9510025).|||Golgi apparatus membrane|||Highly expressed in the central nervous system, including in the brain and spinal cord, in neurons, as well as in glial cells (at protein level) (PubMed:9726247, PubMed:9510025, PubMed:11082041, PubMed:16174740, PubMed:21385844, PubMed:23333276, PubMed:23977241, PubMed:30679749). In the brain, mainly expressed in the cerebellum, hippocampus, dentate gyrus, hypothalamus, and in the cerebral cortex (at protein level) (PubMed:9726247, PubMed:9510025, PubMed:23333276, PubMed:27322061). Also detected in kidney, heart, lung and spleen (PubMed:9726247, PubMed:9510025). In the kidney, expressed in epithelial cells in the thick ascending limb of Henle's loop, the distal convoluted tubule, the connecting tubule and the cortical collecting duct (at protein level) (PubMed:20385770, PubMed:25967121). Expressed in skeletal muscle (at protein level) (PubMed:9726247, PubMed:9510025, PubMed:27322061). Expressed in adipose tissue, including in brown adipose tissue and subcutaneous white adipose tissue (PubMed:26584636, PubMed:27322061). Expressed in intimal smooth muscle cells (at protein level) (PubMed:14764453).|||Knockout mice are viable and fertile with no overt phenotype (PubMed:16174740). They tend to be lighter than their wild-type littermates, with reduced adiposity (PubMed:26584636, PubMed:27322061). On a high-fat diet, they show a reduced gain in body weight compared with wild-type littermates (PubMed:27322061). Mutant animals display improved serum biochemistry profiles compared to wild-type, with lower fasting glucose, insulin and triglyceride levels, particularly on high fat diet (PubMed:26584636, PubMed:27322061). On a high-fat diet, brown adipose tissue from knockout mice shows reduced lipid content and subcutaneous white adipose tissue contains smaller, less lipid replete adipocytes, with increased thermogenic markers (PubMed:26584636). Mutant animals exhibit an increased production of soluble APP and enhanced amount of neuron-associated amyloid-beta protein 40 and 42 in the brain at 10 months of age (PubMed:16174740). Following vascular injury, knockout mice placed on a high-fat diet show reduced intimal thickness and decreased infiltration of lipid-laden macrophages compared to wild-type littermates (PubMed:17332490). Mutant mice display elevated GDNF levels, altered dopaminergic function, marked hyperactivity, and reduced anxiety (PubMed:23333276). Knockout mice show a weak phenotype in the maintenance of renal ion balance. Under basal conditions, they exhibit significant urinary loss of potassium and calcium compared to controls. Serum Na(+), Cl(-), and K(+) levels are normal, but aldosterone levels are elevated 2-fold. Mean arterial blood pressure is decreased despite the hyperaldosteronemic phenotype (PubMed:20385770). The lack of major renal phenotype in mutant mice may be explained by the fact that animals remain responsive to vasopressin endocrine stimulation (PubMed:25967121).|||Phosphorylation at Ser-2207 facilitates the interaction with GGA1.|||Recycling endosome membrane|||Secreted|||Sorting receptor that directs several proteins to their correct location within the cell. Along with AP-1 complex, involved Golgi apparatus - endosome sorting. Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated. May also sort newly produced amyloid-beta peptides to lysosomes for catabolism. Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments (By similarity). Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor (PubMed:23977241). Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion (PubMed:21994944). Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities (PubMed:23333276). Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling (By similarity). Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL (By similarity). Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network (By similarity). Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization (PubMed:27322061). Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB (PubMed:20385770, PubMed:25967121). Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration (By similarity). By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury (PubMed:14764453). Promotes adhesion of monocytes (By similarity). Stimulates proliferation and migration of monocytes/macrophages. Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis (PubMed:17332490). Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain (PubMed:23486467). Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway (PubMed:26584636). May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation (PubMed:26858303). May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R (PubMed:28265003).|||Up-regulated by BDNF in cortical neurons (at protein level) (PubMed:20007471). Up-regulated under hypoxic conditions in hematopoietic stem and progenitor cells, a physiological conditions encountered by these cells in the endosteum (at protein level) (PubMed:23486467). In brown and sucutaneous white adipose tissues, down-regulated when environmental temperature rises from cold to thermoneutrality (PubMed:26584636). Up-regulated in adipose tissue by insulin through a post-transcriptional mechanism (PubMed:27322061). Expression levels increase in the fed state and decline after fasting (PubMed:26584636).|||Within the Golgi apparatus, the propeptide may be cleaved off by FURIN or a furin-like protease. After cleavage, the propeptide interacts with the mature protein N-terminus, preventing the association with other ligands. At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain in the extracellular milieu. The shedding may be catalyzed by ADAM17/TACE. Following shedding, PSEN1/presenilin-1 cleaves the remaining transmembrane fragment and catalyzes the release of a C-terminal fragment in the cytosol and of a soluble N-terminal beta fragment in the extracellular milieu. The C-terminal cytosolic fragment localizes to the nucleus.|||multivesicular body membrane|||secretory vesicle membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Spint1 ^@ http://purl.uniprot.org/uniprot/Q9R097 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Inhibitor of HGFAC (By similarity). Inhibits serine protease activity of ST14/matriptase in vitro (By similarity). Inhibits serine protease activity of TMPRSS13, via the BPTI/Kunitz inhibitor 1 domain (By similarity).|||Interacts with HGFAC (By similarity). Interacts with TMPRSS13; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13 (By similarity).|||Secreted|||This inhibitor contains two inhibitory domains. http://togogenome.org/gene/10090:Cxcl16 ^@ http://purl.uniprot.org/uniprot/A2CFE9|||http://purl.uniprot.org/uniprot/Q8BSU2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Glycosylated.|||Induces a strong chemotactic response. Induces calcium mobilization. Binds to CXCR6/Bonzo. Also acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis.|||Membrane|||Widely expressed. Not detected in purified B- and T-cells. http://togogenome.org/gene/10090:Pram1 ^@ http://purl.uniprot.org/uniprot/Q6BCL1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subunit|||Tissue Specificity ^@ Expressed in bone marrow and mature neutrophils. Weakly expressed in macrophages and mast cells.|||Interacts with SKAP2, LCP2 and DBNL. May interact with LYN (By similarity). Interacts with NEK6 (By similarity).|||May be involved in integrin signaling in neutrophils. Binds to PtdIns(4)P.|||May be phosphorylated on tyrosines.|||Mice are healthy and do not display any obvious abnormality. They have normal hematopoietic differentiation.|||The SH3 domain binds to PtdIns(4)P. http://togogenome.org/gene/10090:Stk25 ^@ http://purl.uniprot.org/uniprot/Q9Z2W1 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Golgi apparatus|||Homodimer. Interacts with CTTNBP2NL.|||Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-174, possibly as a consequence of stabilization of dimer formation. The C-terminal non-catalytic region inhibits the kinase activity (By similarity).|||Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration (By similarity). http://togogenome.org/gene/10090:Rdh7 ^@ http://purl.uniprot.org/uniprot/O88451 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts on androgens and retinols, i.e. has steroid 3-alpha- and 17-beta-dehydrogenase and cis/trans-retinol catalytic activities.|||Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum|||Highly expressed in liver. Also expressed in lung, eye, kidney, and brain.|||Microsome http://togogenome.org/gene/10090:Cd40 ^@ http://purl.uniprot.org/uniprot/P27512 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Monomer and homodimer. Interacts with TRAF1, TRAF2 and TRAF6 (By similarity). Interacts with TRAF3 and TRAF5. Interacts with TRAF6 and MAP3K8; the interaction is required for ERK activation.|||Receptor for TNFSF5/CD40LG (By similarity). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (PubMed:12881420).|||Secreted http://togogenome.org/gene/10090:Arhgap35 ^@ http://purl.uniprot.org/uniprot/Q91YM2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, the highest level of expression is in the spinal cord and lower expression levels are seen in the developing brain. At 15.5 dpc, highly expressed in brain, spinal cord and eyes (PubMed:11044403). In developing kidney, at 17.5 dpc, low expression is observed in the glomerulus, while high expression levels are detected in the proximal tubule (PubMed:26859289). At 14.5 dpc, is expressed within the epithelial compartment of the embryonic mammary bud and at lower level in the surrounding stroma and skin. Also expressed at terminal end bunds (TEB) at comparable levels in body and cap cells as well as in fibroblasts and stroma surrounding the TEB (PubMed:21945077).|||Cell membrane|||Cytoplasm|||Deficiency leads to perinatal lethality and defective neural development. One third of the fetuses show exencephaly and spina bifida as well as defective kidney development.|||Expressed in the developing kidneys (PubMed:26859289). Expressed in all regions of the mature nervous system (at protein level) (PubMed:11044403). Detected in neutrophils (at protein level) (PubMed:20675588).|||Interacts with the general transcription factor GTF2I, the interaction sequesters GTF2I in the cytoplasm (By similarity). Interacts with RASA1 (PubMed:16971514).|||N-terminal part (1-266) has GTPase activity. Required for proper cellular localization. Mutation of this region is a severely defective loss of function. Mutants have defective morphogenesis of neural retinal tissue, agenesis of the corpus callosum due to defectuous midline fusion of the cerebral hemispheres (PubMed:11044403). Mutants show defects in axon guidance and fasciculation (PubMed:11283609).|||Nucleus|||Phosphorylation of Tyr-1105 by PTK6 promotes the association with RASA1, inactivating RHOA while activating RAS. Phosphorylation at Tyr-308 by PDGFRA inhibits binding to GTF2I (By similarity). Phosphorylated by PRKCA at Ser-1221 and Thr-1226, induces relocalization from the cytoplasm to regions of plasma membrane ruffling and prevents the binding and substrate specificity regulation by phospholipids (PubMed:11044403). In brain, phosphorylated by FYN and SRC (PubMed:11283609). During focal adhesion formation, phosphorylated by MAPK1 and MAPK3 at the C-terminal region, probably at Ser-1451, Ser-1476, Thr-1480 and Ser-1483. Phosphorylation by MAPK1 and MAPK3 inhibits GAP function and localizes ARGHAP35 away from newly forming focal adhesions and stress fibers in cells spreading on fibronectin (By similarity). Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires priming by MAPK and inhibits RhoGAP activity and modulates polarized cell migration (PubMed:18502760).|||Rho GTPase-activating protein (GAP). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:16971514). This binding is inhibited by phosphorylation by PRKCA (By similarity). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (PubMed:11044403, PubMed:11283609, PubMed:18502760, PubMed:21945077). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (PubMed:16971514). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (PubMed:11283609). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (PubMed:11044403, PubMed:26859289, PubMed:18502760). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (PubMed:21945077). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (By similarity).|||The pG1 pseudoGTPase domain does not bind GTP.|||cilium basal body http://togogenome.org/gene/10090:Foxp2 ^@ http://purl.uniprot.org/uniprot/P58463 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in developing lung, neural, intestinal and cardiovascular tissues. Expressed at a high level in the distal airway epithelium and at a low level in the proximal airway epithelium at 12.5 dpc, and restricted to the distal airway epithelium by 14.5 dpc. In the spinal cord, at 12.5 dpc, expressed in a subset of interneurons dorsal to motor neurons. At 16.5 dpc, expression in the brain is observed in the inner intermediate zone of the neopallial cortex and in the developing cerebral hemispheres. In the gastrointestinal system, at 12.5 expressed in the outer mesodermal layer and in the intestinal epithelium. By 16.5 dpc, expression is restricted to the outer longitudinal muscle layer of the intestine and stomach. In the cardiovascular system, at 14.5 dpc, expressed in the outflow tract region of the developing heart. By 16.5 dpc, observed in the outflow tract and atrium, but not in the ventricles.|||Forms homodimers and heterodimers with FOXP1 and FOXP4. Dimerization is required for DNA-binding (By similarity). Interacts with CTBP1 (PubMed:14701752). Interacts with FOXP1 (By similarity). Interacts with TBR1 (By similarity). Interacts with ZMYM2 (By similarity).|||Highest expression in lung. Lower expression in spleen, skeletal muscle, brain, kidney and small intestine.|||May be due to a competing acceptor splice site.|||Nucleus|||The leucine-zipper is required for dimerization and transcriptional repression.|||Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. http://togogenome.org/gene/10090:Or7d11 ^@ http://purl.uniprot.org/uniprot/Q7TRF3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Possible olfactory or taste receptor. http://togogenome.org/gene/10090:Cyp46a1 ^@ http://purl.uniprot.org/uniprot/Q3US73|||http://purl.uniprot.org/uniprot/Q9WVK8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in high level in the pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, and neuronal cell bodies in layers II/III, V, and VI of the cortex. Expressed in hippocampal and cerebellar interneurons, in retinal ganglion cells, and in a subset of retinal cells localized to the inner nuclear layer (at protein level).|||Microsome membrane|||Mutant mice are deficient in spatial, associative and motor learning.|||P450 monooxygenase that plays a major role in cholesterol homeostasis in the brain. Primarily catalyzes the hydroxylation (with S stereochemistry) at C-24 of cholesterol side chain, triggering cholesterol diffusion out of neurons and its further degradation (PubMed:10377398, PubMed:16505352, PubMed:28190002). By promoting constant cholesterol elimination in neurons, may activate the mevalonate pathway and coordinate the synthesis of new cholesterol and nonsterol isoprenoids involved in synaptic activity and learning (PubMed:16505352). Further hydroxylates cholesterol derivatives and hormone steroids on both the ring and side chain of these molecules, converting them into active oxysterols involved in lipid signaling and biosynthesis (By similarity). Acts as an epoxidase converting cholesta-5,24-dien-3beta-ol/desmosterol into (24S),25-epoxycholesterol, an abundant lipid ligand of nuclear NR1H2 and NR1H3 receptors shown to promote neurogenesis in developing brain (By similarity). May also catalyze the oxidative metabolism of xenobiotics, such as clotrimazole (By similarity).|||Postsynapse|||Presynapse|||dendrite http://togogenome.org/gene/10090:Defb43 ^@ http://purl.uniprot.org/uniprot/Q30KM9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has bactericidal activity.|||Secreted http://togogenome.org/gene/10090:Rarg ^@ http://purl.uniprot.org/uniprot/P18911 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Homodimer (By similarity). Heterodimer with a RXR molecule (By similarity). Binds DNA preferentially as a RAR/RXR heterodimer (By similarity). Forms a complex with PUS1 and the SRA1 RNA in the nucleus.|||In 9.5-12.5 dpc embryos, expression throughout limb bud mesenchyme. This expression overlaps with that of CYP26B1. Also strongly expressed in the caudal and craniofacial regions.|||Nucleus|||Rarg and Rarb double null mice exhibit growth retardation 3 weeks after birth. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed. Isoform 2 mutants appear normal. The Rarg and Cyp26b1 double null mutation is able to partially rescue limb skeletal morphology without restoring normal expression of proximo-distal patterning genes.|||Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors (By similarity). Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function. http://togogenome.org/gene/10090:Tmem154 ^@ http://purl.uniprot.org/uniprot/Q8C4Q9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Gm21425 ^@ http://purl.uniprot.org/uniprot/Q3TTD8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Slc25a37 ^@ http://purl.uniprot.org/uniprot/Q920G8|||http://purl.uniprot.org/uniprot/Q9CQG7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Erythroblasts generated from murine embryonic stem cells null for Slc25a37/Mfrn show maturation arrest with severely impaired incorporation of iron into heme.|||Highly expressed in hematopoietic organs, fetal liver, bone marrow and spleen.|||In the developing embryo, it is first detected at 7.5 dpc in the extraembryonic yolk sac, coincident with the appearance of blood islands. Later, restricted expression is seen in 14.5 dpc fetal liver, the primary source of erythrocyte production in mid-gestation. Expression decreases in the spleen around 4-5 weeks of age, suggesting that it is decreased during splenic lymphocyte maturation.|||Interacts with ACB10; this interaction stabilizes SLC25A37 and enhances the function of SLC25A37 to import mitochondrial iron during erythroid differentiation.|||Membrane|||Mitochondrial iron transporter that specifically mediates iron uptake in developing erythroid cells, thereby playing an essential role in heme biosynthesis.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Olfr765 ^@ http://purl.uniprot.org/uniprot/Q7TRI6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stimate ^@ http://purl.uniprot.org/uniprot/Q3UF25 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a regulator of store-operated Ca(2+) entry (SOCE) at junctional sites that connect the endoplasmic reticulum (ER) and plasma membrane (PM), called ER-plasma membrane (ER-PM) junction or cortical ER. SOCE is a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts by interacting with STIM1, promoting STIM1 conformational switch. Involved in STIM1 relocalization to ER-PM junctions. Contributes to the maintenance and reorganization of store-dependent ER-PM junctions.|||Belongs to the STIMATE family.|||Endoplasmic reticulum membrane|||Homooligomer. Interacts with STIM1.|||The GXXXG motif may mediate oligomerization. The C-terminus is necessary for its localization at ER-plasma membrane (ER-PM) junctions as well as for the store-dependent rearrangement of ER-PM junctions.|||Widely expressed. http://togogenome.org/gene/10090:Prr19 ^@ http://purl.uniprot.org/uniprot/B2RW88 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Interacts with CNTD1.|||Mice are unfertile in both sexes. Testis weight is significantly lower. Mice males show a depletion of late prophase spermatocytes. are depleted of post-meiotic cells and their weight is significantly lower.|||Nucleus|||Preferentially expressed in gonads.|||Promotes meiotic crossing over formation through its interaction with CNTD1 by participating in the crossover differentiation step of crossover-specific recombination intermediates. http://togogenome.org/gene/10090:Or4d10 ^@ http://purl.uniprot.org/uniprot/Q7TQS1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Etv5 ^@ http://purl.uniprot.org/uniprot/Q9CXC9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Binds to DNA sequences containing the consensus nucleotide core sequence 5'-GGAA.-3'.|||In the brain, expressed predominantly in the cerebral cortex, the amygdala and the hypothalamus. Within the cerebral cortex, there is conspicuously high expression in cortical layers 2, 4 and 6 while expression is almost absent from layers 1, 3 and 5. High expression is also observed in the dorsal and ventral endopiriform claustrum. Strong expression is observed in limited parts of the amygdala including the basolateral amygdaloid nucleus, the bed stria terminalis and the central amygdaloid nucleus. Low to moderate levels are found in the hypothalamus while expression is almost absent in the thalamus. Hypothalamic expression is seen in the dorsomedial hypothalamic nucleus and also the central, dorsomedial and ventrolateral parts of the ventromedial hypothalamic nucleus. Strong expression is also identified in the nigrostriatal tract. In the mesencephalon, expression is restricted to the ventral tegmental area including the parabrachial pigmented nucleus. In the hippocampus, strongly expressed in the pyramidal cell layer. Some expression is also found in the lacunosum moleculare layer. Low levels of expression in the cerebellum, including the granular, molecular and Purkinje cell layers.|||Interacts (via C-terminal) with ZMYM5 (via N-terminal 120 amino acid region).|||Nucleus http://togogenome.org/gene/10090:Lrrc34 ^@ http://purl.uniprot.org/uniprot/Q9DAM1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in unfertilized oocytes; expression continues in preimplantation embryos though to the blastula stage (at protein level) (PubMed:24991885). In testis, detected in very early spermatogonial germ cells with expression continuing through to the elongated spermatid stage (at protein level) (PubMed:24435972, PubMed:24991885). Weakly expressed in spermatozoa (at protein level) (PubMed:24435972). Not detected in spermatozoa (at protein level) (PubMed:24991885).|||Expressed in testis where it specifically localizes to germ cells (at protein level) (PubMed:24435972, PubMed:24991885). Not detected in other tissues tested (at protein level) (PubMed:24435972, PubMed:24991885). Expressed in pluripotent embryonic stem cells and multipotent adult germline stem cells (PubMed:24991885).|||Highly expressed in stem cells where it may be involved in regulation of pluripotency. In embryonic stem cells (ESCs), important for normal expression of the pluripotency regulators POU5F1/OCT4 and KLF4. Also important for expression of the ectodermal marker gene NES and the endodermal marker gene GATA4. Promotes stem cell proliferation in vitro.|||Interacts with NPM1 and NCL.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Rtkn ^@ http://purl.uniprot.org/uniprot/Q8C6B2 ^@ Function|||Subunit|||Tissue Specificity ^@ Abundantly expressed in brain and kidney. Weakly expressed in lung, testis, skeletal muscle, heart and thymus.|||Interacts via its C-terminal region with the TAX1BP3 PDZ domain. This interaction facilitates Rho-mediated activation of the c-Fos serum response element (SRE). Interacts with SEPT9 (By similarity). Specifically binds to GTP-bound RHOA, RHOB and RHOC and inhibits their GTPase activity.|||Mediates Rho signaling to activate NF-kappa-B and may confer increased resistance to apoptosis to cells in gastric tumorigenesis. May play a novel role in the organization of septin structures (By similarity). http://togogenome.org/gene/10090:Ggcx ^@ http://purl.uniprot.org/uniprot/B2RS80|||http://purl.uniprot.org/uniprot/Q9QYC7 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the vitamin K-dependent gamma-carboxylase family.|||Embryonic lethality between 9.5-18 dpc due to massive hemorrhage (PubMed:17327402). Conditional deletion in osteoblasts leads to altered glucose metabolism due to inability to carboxylate osteocalcin (bglap and bglap2) (PubMed:25264202).|||Endoplasmic reticulum membrane|||Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide (By similarity). Catalyzes gamma-carboxylation of various proteins, such as blood coagulation factors (F2, F7, F9 and F10), osteocalcin (bglap and bglap2) or matrix Gla protein (MGP) (PubMed:25264202).|||Membrane|||Monomer (By similarity). May interact with CALU (By similarity).|||The vitamin K-dependent protein substrates of carboxylase have usually a propeptide that binds to a high-affinity site on the carboxylase. CO(2), O(2) and reduced vitamin K are cosubstrates. http://togogenome.org/gene/10090:Gnat1 ^@ http://purl.uniprot.org/uniprot/P20612 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||Functions as signal transducer for the rod photoreceptor RHO. Required for normal RHO-mediated light perception by the retina (By similarity). Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs), such as the photoreceptor RHO. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Activated RHO promotes GDP release and GTP binding. Signaling is mediated via downstream effector proteins, such as cGMP-phosphodiesterase (By similarity).|||Heterotrimeric G proteins are composed of 3 subunits alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with RHO. Interacts with RGS9 and PDE6G (By similarity). Interacts (when myristoylated) with UNC119; interaction is required for localization in sensory neurons (By similarity).|||In the retina, expressed in the rod photoreceptors.|||Membrane|||Photoreceptor inner segment|||photoreceptor outer segment http://togogenome.org/gene/10090:Faim2 ^@ http://purl.uniprot.org/uniprot/Q8K097 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiapoptotic protein which protects cells uniquely from Fas-induced apoptosis. Regulates Fas-mediated apoptosis in neurons by interfering with caspase-8 activation. Plays a role in cerebellar development by affecting cerebellar size, internal granular layer (IGL) thickness, and Purkinje cell (PC) development.|||Belongs to the BI1 family. LFG subfamily.|||Brain. Highly expressed in cerebellum, also found in cortex, olfactory bulb, and hippocampus.|||Cell membrane|||Interacts with FAS/TNFRSF6 and BAX.|||Membrane raft|||Mice show reduced cerebellar size and internal granular layer (IGL) thickness in early developmental stages, delayed Purkinje Cell (PC) development, with an abnormal morphology and reduced cellular density, increased caspase-8 and caspase-3 activity in PCs and higher sensitivity to Fas-mediated apoptosis.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Glis2 ^@ http://purl.uniprot.org/uniprot/Q8VDL9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GLI C2H2-type zinc-finger protein family.|||C-terminus cleavage is induced by interaction with CTNND1 and enhances by Src tyrosine kinase.|||Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context. Acts as a repressor of the Hedgehog signaling pathway. Represses the Hedgehog-dependent expression of Wnt4. Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition. Represses transcriptional activation by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation.|||Cytoplasm|||Expressed at high levels in kidney, and at lower levels in heart and lung.|||Expression begins at 9.5 dpc in cranial ganglia, dorsal root ganglia and neural tube. At 10.5 dpc, broadly expressed in the intermediate zone of the hindbrain, spinal cord and dorsal root ganglia. By 12.5 dpc, expression in the spinal cord becomes restricted to a narrow band of cells in the ventricular zone.|||Interacts with CTBP1 and HDAC3. Interacts with CTNNB1 and CTNND1. Interacts with SUFU.|||Nucleus speckle|||The C2H2-type zinc finger 1 has a major repressor function and is required for CTNNB1 binding. http://togogenome.org/gene/10090:Tomm20 ^@ http://purl.uniprot.org/uniprot/Q4KL41|||http://purl.uniprot.org/uniprot/Q9DCC8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Tom20 family.|||Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the TOM40 translocation pore (By similarity). Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases.|||Expressed in brain, kidney, stomach, colon, jejunum, ileum, testis, ovary and oviduct (at protein level) (PubMed:19492028). In the brain, expressed in neural cells of the cerebrum and cerebellum (at protein level) (PubMed:19492028). In the kidney, expressed in the proximal to distal tubule in the cortex and the outer and inner zones of the medulla (at protein level) (PubMed:19492028). In the stomach, expressed in the basal layer of stratified squamous epithelia in the forestomach and in the gastric pit and fundic gland of the glandular stomach (at protein level) (PubMed:19492028). Expressed in epithelial cells of the jejunum, ileum, and colon (at protein level) (PubMed:19492028). In the testis, expressed by spermatocytes and spermatogonia (at protein level) (PubMed:19492028). In the ovaries, expressed by follicular epithelial cells and corpus luteum cells (at protein level) (PubMed:19492028). In the oviduct, expressed in the epithelia of the isthmus and the ciliated cells of the ampulla (at protein level) (PubMed:19492028). Expressed in the sperm midpiece (at protein level) (PubMed:19492028, PubMed:32976492).|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70). Interacts with TOM22. Interacts with APEX1 (By similarity). Interacts with TBC1D21 (PubMed:32976492).|||Membrane|||Mitochondrion outer membrane|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Lbh ^@ http://purl.uniprot.org/uniprot/Q9CX60 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LBH family.|||Cytoplasm|||Expressed at highest levels in heart, and at lower levels in brain, spleen, lung, liver and kidney.|||First detected at 7.5 dpc in the mesendoderm that forms the anterior gut and the heart. At midgestation, expressed in the limb bud ectoderm and other specialized epithelia, as well as in the branchial arches and some neural crest derivatives. In the heart, expression initiates in the myocardial plate at the presomitic stage, with highest levels in the anterior myocardium. During heart chamber formation, expressed transiently in the right ventricle, atrioventricular canal and inflow tract. In the limb bud, expression is restricted to the ventral ectodermal compartment and the apical ectodermal ridge.|||Mice overexpressing Lbh in heart exhibit severe cardiac abnormalities and dysfunction.|||Modulates the activity of key transcription factors involved in cardiogenesis.|||Nucleus http://togogenome.org/gene/10090:Spata32 ^@ http://purl.uniprot.org/uniprot/Q8C5V0 ^@ Subunit|||Tissue Specificity ^@ Highly expressed in the testis and weakly in the brain and heart.|||Interacts with syntaxin-1 and ACTB. http://togogenome.org/gene/10090:Ppargc1a ^@ http://purl.uniprot.org/uniprot/O70343 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Dramatically induced in brown adipose tissue and skeletal muscle by exposure of animals to cold. Up-regulated in brown adipose tissue of obese leptin-deficient (ob/ob) and leptin-unresponsive (db/db) mice. Leptin is required for normal basal and cold-stimulated expression in brown adipose tissue and hyperleptinemia rapidly up-regulates its expression. Induced in muscle by exercise. Oscillates diurnally in liver and skeletal muscle.|||Heavily acetylated by KAT2A/GCN5 under conditions of high nutrients, leading to inactivation of PPARGC1A (PubMed:15744310). Deacetylated by SIRT1 in low nutrients/high NAD conditions, leading to its activation (PubMed:15716268, PubMed:15744310).|||Homooligomer (By similarity). Interacts with MYBBP1A; inhibits MYBBP1A transcriptional activation (PubMed:14744933). Interacts with PRDM16, LPIN1 and PML (PubMed:16950137, PubMed:17618855, PubMed:18483224, PubMed:22886304). Interacts (via LXXLL motif) with RORA and RORC (via AF-2 motif); activates RORA and RORC transcriptional activation (PubMed:17476214). Interacts with LRPPRC (By similarity). Interacts with FOXO1 (PubMed:12754525).|||Mice show abnormal diurnal rhythms of activity, body temperature and metabolic rate.|||Nucleus|||PML body|||Phosphorylation by AMPK in skeletal muscle increases activation of its own promoter (PubMed:17609368). Phosphorylated by CLK2 (PubMed:20074525).|||Produced by alternative promoter usage and alternative splicing.|||Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:15744310, PubMed:12754525, PubMed:23217713, PubMed:9529258). Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter (PubMed:15744310, PubMed:12754525, PubMed:23217713, PubMed:9529258). Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis (PubMed:15744310, PubMed:12754525, PubMed:23217713, PubMed:9529258). Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism (PubMed:15744310, PubMed:12754525, PubMed:23217713, PubMed:9529258). Acts as a key regulator of gluconeogenesis: stimulates hepatic gluconeogenesis by increasing the expression of gluconeogenic enzymes, and acting together with FOXO1 to promote the fasting gluconeogenic program (PubMed:12754525). Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner (By similarity). Also involved in the integration of the circadian rhythms and energy metabolism (PubMed:17476214). Required for oscillatory expression of clock genes, such as BMAL1 and NR1D1, through the coactivation of RORA and RORC, and metabolic genes, such as PDK4 and PEPCK (PubMed:17476214).|||Ubiquitinated. Ubiquitination by RNF34 induces proteasomal degradation.|||White quadriceps and red tibialis anterior (TA) muscles, liver, kidney and brown adipose tissue (at protein level). Skeletal muscle, brown adipose tissue, heart, kidney and brain. http://togogenome.org/gene/10090:Afp ^@ http://purl.uniprot.org/uniprot/P02772 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ALB/AFP/VDB family.|||Binds estrogens, fatty acids and metals.|||Glycosylated; contains two glycans.|||Plasma.|||Secreted|||Sulfated. http://togogenome.org/gene/10090:Pih1d1 ^@ http://purl.uniprot.org/uniprot/Q9CQJ2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIH1 family.|||Component of the R2TP complex composed at least of RUVBL1, RUVBL2, RPAP3 and PIHD1 (By similarity). Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (By similarity). Interacts with phosphorylated TELO2 (PubMed:24794838). Mediates interaction of TELO2 with the R2TP complex (By similarity). Interacts with phosphorylated ECD, EFTUD2/SNRP116, RPB1 and UBR5 and with RPB1 in a phosphorylation-independent manner (By similarity). Interacts with the core C/D box snoRNP particle components NOP58 and FBL and with RUVBL1/TIP49 (By similarity). Interacts with RPAP3 and DNAAF10 (By similarity). Interacts with histone H4 and with SWI/SNF complex member SMARCB1/SNF5 (By similarity). Interacts with the mTORC1 complex member RPTOR (By similarity). Interacts with isoform 1 of MSL1 (PubMed:17335777).|||Involved in the assembly of C/D box small nucleolar ribonucleoprotein (snoRNP) particles (By similarity). Recruits the SWI/SNF complex to the core promoter of rRNA genes and enhances pre-rRNA transcription (By similarity). Mediates interaction of TELO2 with the R2TP complex which is necessary for the stability of MTOR and SMG1 (By similarity). Positively regulates the assembly and activity of the mTORC1 complex (By similarity).|||Nucleus|||The N-terminal region is required for binding to phosphorylated substrates while the C-terminal region binds to the other R2TP complex components. http://togogenome.org/gene/10090:Vmn2r94 ^@ http://purl.uniprot.org/uniprot/E9PZK8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Scn8a ^@ http://purl.uniprot.org/uniprot/A0A0J9YUW5|||http://purl.uniprot.org/uniprot/A0A0R5RP22|||http://purl.uniprot.org/uniprot/F6U329|||http://purl.uniprot.org/uniprot/F7D6J5|||http://purl.uniprot.org/uniprot/F7D6K4|||http://purl.uniprot.org/uniprot/Q9WTU3 ^@ Activity Regulation|||Caution|||Disease Annotation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.|||Cell membrane|||Defects in Scn8a are a cause of degenerating muscle (dmu). Dmu is an autosomal recessive neuromuscular disorder that is characterized by skeletal and cardiac muscle degeneration. It produces early onset progressive loss of mobility of the hind limbs and subsequent lethality in the first month of life.|||Defects in Scn8a are the cause of motor endplate disease (med). Med is a recessive neuromuscular disorder that is characterized by lack of signal transmission at the neuromuscular junction, excess preterminal arborization and degeneration of cerebellar Purkinje cells. It produces early onset progressive paralysis of hind limbs, severe muscle atrophy and juvenile lethality.|||Defects in Scn8a are the cause of the jolting mutant (medjo), a mild form of motor endplate disease which is characterized by the absence of spontaneous, regular, simple discharges from Purkinje cells. After 3 weeks of age, jolting mice are unsteady and have wide-based gait and a rhythmical tremor of head and neck induced by attempted movement.|||Due to aberrant splicing.|||Expressed in the hippocampus (at protein level) (PubMed:28842554). Expressed in brain, cerebellum and spinal cord. Isoform 5: May be expressed in non-neuronal tissues, such as peritoneal macrophages.|||Inhibited by tetrodotoxin and, more weakly, by its metabolite 4,9-ah-tetrodotoxin.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May be ubiquitinated by NEDD4L; which would promote its endocytosis.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages, isoform 5 may participate in the control of podosome and invadopodia formation.|||Membrane|||Phosphorylation at Ser-1495 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.|||The voltage-sensitive sodium channel consists of an ion-conducting pore-forming alpha subunit regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B) subunits. Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by disulfide bonds. Interacts with FGF13 (By similarity). Interacts with NEDD4 and NEDD4L (PubMed:15123669). Interacts with FGF14, GBG3, GBB2 and SCN1B (By similarity). Interacts with the conotoxin GVIIJ (By similarity). Interacts with the scorpion toxin BMK M1 (PubMed:20678086). Interacts with CALM1; the interaction modulates the inactivation rate of SCN8A (PubMed:23942337).|||axon http://togogenome.org/gene/10090:Mov10l1 ^@ http://purl.uniprot.org/uniprot/Q99MV5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent RNA helicase required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for germline integrity (PubMed:20534472, PubMed:20547853, PubMed:23166510, PubMed:25762440). Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:20534472, PubMed:20547853, PubMed:23166510, PubMed:25762440). Involved in the primary piRNA metabolic process (PubMed:20534472, PubMed:20547853, PubMed:23166510, PubMed:25762440). Specifically binds to piRNA precursors and promotes the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins (PubMed:25762440). Acts via its ATP-dependent RNA helicase activity: displays 5'-3' RNA unwinding activity and probably mediates unwinding and funneling of single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing to generate piRNA intermediate fragments that are subsequently loaded to Piwi proteins (PubMed:25762440).|||Belongs to the DNA2/NAM7 helicase family. SDE3 subfamily.|||Cytoplasm|||Expression is first observed in the linear heart tube at 8 dpc. The highest expression is in the region that will give rise to the ventricular segments. At 9.5 dpc, the ventricular expression is maintained in the looped heart tube. In the adult, expression is observed exclusively within myocardial cells.|||Interacts with PIWIL1 (PubMed:20534472). Interacts with PIWIL2 (PubMed:20534472, PubMed:20547853). Interacts with PIWIL4 (PubMed:20534472, PubMed:20547853). Interacts with HSPA2 (PubMed:20547853). Interacts with PLD6 (PubMed:25762440).|||Isoform 1: Specifically expressed in testis (PubMed:12754203). Isoform 1: In testis, present in pachytene spermatocytes but absent in postmeiotic spermatids (at protein level) (PubMed:20534472, PubMed:20547853). Isoform 2: Present in cardiomyocytes (at protein level) (PubMed:11279525). Isoform 2: Heart specific (PubMed:11854500). Isoform 3: Heart specific and is specifically expressed in cardiac myocytes (PubMed:12754203).|||Isoform 2: Activated by MEF2C. Isoform 3: Activated by Nkx2-5.|||May act downstream of MEF2C during heart formation. Acts as a cardiac-specific suppressor of cardiomyocyte hypertrophy and cell cycle progression, suggesting that it may suppress these processes through the regulation of CDKN1A. Such results however require additional evidence.|||Mice are viable and healthy but show male sterility due to defects in spermatogenesis at early prophase of meiosis I (PubMed:20534472, PubMed:20547853, PubMed:23166510). Retrotransposons are derepressed due to DNA demethylation (PubMed:20534472). Defects are caused by impaired piRNA biogenesis during pachytene (PubMed:20534472, PubMed:20547853). The absence of pachytene piRNAs causes disruption of germ cell development and results in defects in post-meiotic genome integrity (PubMed:23166510). Mice do not show any cardiac abnormalities (PubMed:20547853). http://togogenome.org/gene/10090:Aqr ^@ http://purl.uniprot.org/uniprot/A2AQA7|||http://purl.uniprot.org/uniprot/Q8CFQ3 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWF11 family.|||By retinoic acid (RA).|||Contains an N-terminal domain with structural similarity to ARM repeat regions; this domain functions as scaffold for protein-protein interactions, but is not required for RNA binding or for ATP-dependent RNA helicase activity.|||First detected at 8.5 dpc, when neural crest cells are visible at the lateral ridges of the neural plate. During embryogenesis, it is expressed in mesoderm, in the neural crest (and its target tissues) and in neuroepithelium.|||Identified in the spliceosome C complex. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE.|||Identified in the spliceosome C complex. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex. The IB complex does not contain PRPF19. Within the spliceosome, interacts with SNRPA1, SF3B1, SF3B3, SF3A1 and SF3A2.|||Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis. Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly. May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing.|||Involved in pre-mRNA splicing as component of the spliceosome. Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis. Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly. May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing. Has ATP-dependent RNA helicase activity and can unwind double-stranded RNA molecules with a 3' overhang (in vitro).|||Nucleus|||nucleoplasm http://togogenome.org/gene/10090:C1rl ^@ http://purl.uniprot.org/uniprot/Q3UZ09 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Expressed in liver (at protein level).|||Mediates the proteolytic cleavage of HP/haptoglobin in the endoplasmic reticulum.|||Secreted http://togogenome.org/gene/10090:Rspo2 ^@ http://purl.uniprot.org/uniprot/Q8BFU0 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Probably also acts as a ligand for frizzled and LRP receptors (PubMed:21693646). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form (By similarity).|||Belongs to the R-spondin family.|||Detected from day 9.5 in various neural and mesodermal derivatives, mainly along diencephalon. Strongly expressed in limb buds, particularly in the morphogenetically active region such as the apical ectodermal ridge (AER).|||Interacts with WNT1 (PubMed:16543246). Binds heparin (PubMed:16543246). Interacts with LGR4, LGR5 and LGR6 (PubMed:21693646).|||Secreted|||The FU repeat is required for activation and stabilization of beta-catenin. http://togogenome.org/gene/10090:Pcgf1 ^@ http://purl.uniprot.org/uniprot/Q8R023 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the Polycomb group (PcG) multiprotein BCOR complex, a complex required to maintain the transcriptionally repressive state of some genes, such as BCL6 and the cyclin-dependent kinase inhibitor, CDKN1A. Transcriptional repressor that may be targeted to the DNA by BCL6; this transcription repressor activity may be related to PKC signaling pathway. Represses CDKN1A expression by binding to its promoter, and this repression is dependent on the retinoic acid response element (RARE element). Promotes cell cycle progression and enhances cell proliferation as well. May have a positive role in tumor cell growth by down-regulating CDKN1A. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity. Regulates the expression of DPPA4 and NANOG in the NT2 embryonic carcinoma cells.|||Expressed in the otic vesicle, urogenital bud and dorsal root ganglia at 10.5 dpc, in the neural tube and neural crest cell derivatives of the peripheral nervous system at 11.5 dpc.|||Interacts with BCORL1, forming heterodimers (By similarity). The PCGF1-BCORL1 heterodimeric complex interacts with the KDM2B-SKP1 heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (By similarity). Component of the repressive BCOR complex containing a Polycomb group subcomplex at least composed of RYBP, RING1 and RNF2/RING2 (By similarity). Specifically interacts with BCOR, RING1 and RNF2/RING2 (By similarity). Component of a PRC1-like complex (By similarity). Interacts with CBX6, CBX7 and CBX8 (By similarity). Interacts with DPPA4, NANOG, POU5F1 and RYBP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Trim38 ^@ http://purl.uniprot.org/uniprot/Q5SZ99 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 ubiquitin-protein and E3 SUMO-protein ligase that acts as a regulator of innate immunity (PubMed:22539786, PubMed:26392463, PubMed:27637147). Acts as a negative regulator of type I interferon IFN-beta production by catalyzing 'Lys-48'-linked polyubiquitination of AZI2/NAP1, leading to its degradation (PubMed:22539786). Mediates 'Lys-48'-linked polyubiquitination and proteasomal degradation of the critical TLR adapter TICAM1, inhibiting TLR3-mediated type I interferon signaling (PubMed:26392463). Acts as positive regulator of the cGAS-STING pathway by acting as a E3 SUMO-protein ligase: mediates sumoylation of CGAS and STING, preventing their degradation and thereby activating the innate immune response to DNA virus (PubMed:27637147). Also acts as a negative regulator of NF-kappa-B signaling independently of its E3 protein ligase activity by promoting lysosome-dependent degradation of TAB2 and TAB3 adapters (By similarity).|||Interacts (via B30.2/SPRY domain) with TAB2 and TAB3.|||Mice are more susceptible to death triggered by polyinosinic:polycytidylic acid, LPS and S.typhimurium (PubMed:26392463). Increased TLR3/4-mediated cytokine induction (PubMed:26392463). http://togogenome.org/gene/10090:Klk1b26 ^@ http://purl.uniprot.org/uniprot/P36369 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.|||Prorenin-converting enzyme cleaves mouse REN-2 prorenin at a dibasic site to yield mature renin. http://togogenome.org/gene/10090:Tmem220 ^@ http://purl.uniprot.org/uniprot/Q8BP07 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Duox1 ^@ http://purl.uniprot.org/uniprot/A2AQ92 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.|||In the N-terminal section; belongs to the peroxidase family.|||Membrane http://togogenome.org/gene/10090:Prl2c3 ^@ http://purl.uniprot.org/uniprot/A0A0M5HDY5|||http://purl.uniprot.org/uniprot/P04768 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Endoplasmic reticulum|||Expressed during hair follicle morphogenesis, with highest expression levels detected at late anagen stage of the hair follicle cycle (PubMed:11316781). Expressed in developing brain from embryo to adult (PubMed:16876275). In placenta, detected at 8 dpc, peaks at 10 dpc and declines thereafter (PubMed:10537154).|||Expressed in placenta and hair follicles, with highest expression levels detected in the outer root sheath and no expression detected in bulb (PubMed:11316781). Expressed in placenta, skin wounds, keratinocytes and weakly in embryonic fibroblasts (PubMed:10537154, PubMed:11316781, PubMed:16876275). Expressed in brain, cerebellum and in Neuro-2a cell line (PubMed:16876275). Not detected in liver, kidney, ovary, pituitary gland and brain (PubMed:3859868).|||May have a role in embryonic development. It is likely to provide a growth stimulus to target cells in maternal and fetal tissues during the development of the embryo at mid-gestation. May play a role during wound healing and in the hair follicle cycle as a growth factor and/or an angiogenesis factor. May play a role in microvilli formation and cell proliferation of neuroblastoma cells.|||N-glycosylated and sialylated.|||Prl2c3 and Prl2c4 have previously been regarded as different proteins, but they seem to be products of the same gene.|||Secreted http://togogenome.org/gene/10090:Pstpip2 ^@ http://purl.uniprot.org/uniprot/Q99M15 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds to F-actin. May be involved in regulation of the actin cytoskeleton.|||Cytoplasm|||Expressed in macrophage-containing tissues, including bone marrow, spleen, liver, kidney, intestine and brain.|||Membrane|||Phosphorylated on tyrosine. http://togogenome.org/gene/10090:Sfr1 ^@ http://purl.uniprot.org/uniprot/Q8BP27 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SFR1/MEI5 family.|||Component of the SWI5-SFR1 complex (PubMed:20976249). Interacts with RAD51; the interaction is weak (By similarity).|||Component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination (PubMed:20976249). Acts as a transcriptional modulator for ESR1.|||Nucleus http://togogenome.org/gene/10090:Fut2 ^@ http://purl.uniprot.org/uniprot/A6H6C9|||http://purl.uniprot.org/uniprot/Q9JL27 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 11 family.|||Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose on both O- and N-linked glycans chains of cell surface glycoproteins and glycolipids and the resulting epitope regulates several processes such as cell-cell interaction including host-microbe interaction, cell surface expression and cell proliferation (PubMed:11018479, PubMed:11368156, PubMed:14967068, PubMed:11323419, PubMed:27161092, PubMed:19706747). Preferentially fucosylates gangliosides GA1 and GM1 in the antrum, cecum and colon and in the female reproductive organs (PubMed:11713270, PubMed:14967068). Fucosylated host glycoproteins or glycolipids mediate interaction with intestinal microbiota influencing its composition (PubMed:27161092, PubMed:19706747). Creates a soluble precursor oligosaccharide FuC-alpha ((1,2)Galbeta-) called the H antigen which is an essential substrate for the final step in the soluble ABO blood group antigen synthesis pathway (PubMed:11323419).|||Detected at highest levels in proestrus and estrus, with 10- to 12-fold increases over early diestrus.|||Expressed in stomach, colon, ovary and uterus, specifically in luminal uterine epithelium (PubMed:11323419, PubMed:11368156). Expressed in various tissues including heart, liver, kidney, testis, epididymis, small intestine,and cecum (PubMed:11368156). Expressed in duodenum, jejunum and ileum (PubMed:14967068).|||Golgi stack membrane|||Homozygous knockout mice for FUT2 are fertiles and develop normally and exhibit no gross phenotypic abnormalities.|||In mouse, there are three genes (Fut1, Fut2 and Sec1) which encode galactoside 2-L-fucosyltransferase.|||Induced after microbes administration in the intestinal epithelia, particularly in the duodenal and jejunal epithelia (PubMed:11368156, PubMed:14967068). Down-regulated by androgen in the caput epididymis (PubMed:24284406).|||Membrane http://togogenome.org/gene/10090:Gm20834 ^@ http://purl.uniprot.org/uniprot/J3QM72 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:H4c8 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Tcl1b4 ^@ http://purl.uniprot.org/uniprot/P56844 ^@ Similarity ^@ Belongs to the TCL1 family. http://togogenome.org/gene/10090:Acbd7 ^@ http://purl.uniprot.org/uniprot/Q9D258 ^@ Function|||Similarity ^@ Belongs to the ACBD7 family.|||Binds medium- and long-chain acyl-CoA esters. http://togogenome.org/gene/10090:Usp48 ^@ http://purl.uniprot.org/uniprot/A2ALR9|||http://purl.uniprot.org/uniprot/Q3V0C5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Cytoplasm|||Interacts with TRAF2 and RELA.|||Nucleus|||Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. May be involved in the regulation of NF-kappa-B activation by TNF receptor superfamily via its interactions with RELA and TRAF2. May also play a regulatory role at postsynaptic sites (By similarity). http://togogenome.org/gene/10090:Dnttip2 ^@ http://purl.uniprot.org/uniprot/Q8R2M2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Forms a ternary complex with DNTT and core histone; interaction with PCNA releases DNTT and H2A/H2B histones from this ternary complex. Interacts with ESR1, ESR2, PPARG and RXRA. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Nucleus|||Regulates the transcriptional activity of DNTT and ESR1. May function as a chromatin remodeling protein. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Krtap26-1 ^@ http://purl.uniprot.org/uniprot/Q9D7N2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).|||Interacts with hair keratins. http://togogenome.org/gene/10090:Ptpn13 ^@ http://purl.uniprot.org/uniprot/G5E8B1|||http://purl.uniprot.org/uniprot/Q64512 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Expressed predominantly in kidney and, to a lesser extent, in lung, heart, brain and testis.|||Interacts (via the first PDZ domain) with PLEKHA1 and PLEKHA2. Interacts (via the second PDZ domain) with TNFRSF6 (Fas receptor) (via C-terminus) (By similarity). Interacts (via the second PDZ domain) with TRIP6 (via the third LIM domain and C-terminus) (PubMed:10826496). Interacts (via the third PDZ domain) with NGFR (via C-terminal SVP motif) and PKN2 (via C-terminus) (By similarity). Interacts (via the second or fourth PDZ domains) with PDLIM4 (via C-terminus only or via combined C-terminus and LIM domain, but not LIM domain only) (PubMed:9487134, PubMed:15663004). Found in a complex with PDLIM4 and TRIP6 (PubMed:10826496). Interacts with PDLIM4; this interaction results in dephosphorylation of SRC 'Tyr-419' by this protein leading to its inactivation (By similarity). Interacts with BRD7 (PubMed:10526152). Interacts with RAPGEF6. Interacts with ARHGAP29. Interacts with PIK3R2; dephosphorylates PIK3R2. Interacts with FBXL2 (By similarity). Interacts (via the FERM domain) with ENTR1 (PubMed:23108400). Found in a complex with ENTR1, PTPN13 and GIT1 (PubMed:23108400).|||Nucleus|||Regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling.|||Tyrosine phosphatase which regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling. May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2.|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Mbl1 ^@ http://purl.uniprot.org/uniprot/P39039 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-dependent lectin. Plays a role in the innate immune response by binding mannose, fucose and N-acetylglucosamine moieties on different microorganisms and mediating activation of the lectin complement pathway (By similarity). Binds to late apoptotic cells, as well as to apoptotic blebs and to necrotic cells, but not to early apoptotic cells, facilitating their uptake by macrophages (By similarity).|||Detected in liver and blood serum (at protein level) (PubMed:1637828, PubMed:25419660). Detected in liver (PubMed:1712818).|||Homotrimer (By similarity). Forms higher oligomeric complexes formed by the association of two, three or more homotrimers (PubMed:25419660). Oligomerization occurs in the endoplasmic reticulum (By similarity). Interacts with MASP1 and MASP2 (By similarity).|||Hydroxylated on lysine and proline residues within the collagen-like domain.|||May be due to competing donor splice site.|||O-glycosylated. O-linked glycans on hydroxylysine residues consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups.|||Secreted|||The helical collagen-like domains from three protein chains assemble into a coiled coil and mediate trimerization. http://togogenome.org/gene/10090:Ppp3r1 ^@ http://purl.uniprot.org/uniprot/Q63810 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcineurin regulatory subunit family.|||Cell membrane|||Expressed in osteoblasts and bone marrow (at protein level) (PubMed:16286645). Expressed in the brain, kidney, liver, lung, muscle, ovary, spleen, thymus, heart and testis (PubMed:1325794).|||Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B) (PubMed:26794871). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2). The regulatory subunit confers calcium sensitivity. Interacts with catalytic subunit PPP3CA/calcineurin A (PubMed:26794871). Interacts with catalytic subunit PPP3CB/calcineurin A (By similarity). Isoform 1 and isoform 2 interact with CIB1 (via C-terminal region); the interaction increases upon cardiomyocyte hypertrophy (PubMed:20639889). Interacts with SPATA33 (via PQIIIT motif) (By similarity).|||Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.|||This protein has four functional calcium-binding sites.|||cytosol|||sarcolemma http://togogenome.org/gene/10090:Spred1 ^@ http://purl.uniprot.org/uniprot/Q924S8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in brain. Weakly expressed in lung, heart, liver, kidney, intestine, spleen, testis, thymus, colon and ovary. Also expressed in embryonic tissues such as heart, lung, liver and brain. Highly expressed in IL3-dependent hematopoietic cell lines (Ba/F3 and MC/9) and bone marrow-derived mast cells (BMMC).|||Homodimer and heterodimer (By similarity). Able to interact with SPRED2 to form heterodimers (By similarity). Interacts (via C-terminus) with TAOK1/MARKK (via C-terminus); the interaction does not affect TAOK1 kinase activity (By similarity). Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction inhibits TESK1 kinase activity (PubMed:17974561). Interacts with CAV1 (By similarity). Interacts with RAS (PubMed:11493923). Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction leads to palmitoylation of SPRED1 (PubMed:24705354).|||Nucleus|||Palmitoylated by ZDHHC17/HIP14.|||Phosphorylated on tyrosine.|||Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase (PubMed:11493923). Negatively regulates hematopoiesis of bone marrow (PubMed:15465815). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (PubMed:29501879). Attenuates actin stress fiber formation via inhibition of TESK1-mediated phosphorylation of cofilin (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (PubMed:25576668).|||Ubiquitinated.|||caveola http://togogenome.org/gene/10090:Mrpl45 ^@ http://purl.uniprot.org/uniprot/Q9D0Q7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL45 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Or2i1 ^@ http://purl.uniprot.org/uniprot/Q6UAH0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Thumpd2 ^@ http://purl.uniprot.org/uniprot/Q9CZB3 ^@ Similarity|||Subunit ^@ Belongs to the methyltransferase superfamily.|||Interacts with TRMT112. http://togogenome.org/gene/10090:Neurog2 ^@ http://purl.uniprot.org/uniprot/P70447 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Nucleus|||Transcriptional regulator. Involved in neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). http://togogenome.org/gene/10090:Olfml2a ^@ http://purl.uniprot.org/uniprot/B2RQD8|||http://purl.uniprot.org/uniprot/Q8BHP7 ^@ Caution|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in lung, eye, testis, uterus, ovary, and to a lesser extent in heart, skeletal muscle, mammary gland, skin and prostate. Within the eye, mainly present in photoreceptor layers (at protein level).|||Homodimer. Binds to heparin and chondroitin sulfate E.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||O-glycosylated but not N-glycosylated.|||Secreted|||Seems to be cleaved at Lys-301 after secretion. http://togogenome.org/gene/10090:Elapor1 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQC6|||http://purl.uniprot.org/uniprot/A2AFS3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ELAPOR family.|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with HSPA5; may regulate the function of HSPA5 in apoptosis and cell proliferation.|||Late endosome membrane|||Lysosome membrane|||May protect cells from cell death by inducing cytosolic vacuolization and up-regulating the autophagy pathway. May play a role in apoptosis and cell proliferation through its interaction with HSPA5.|||Membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Crhr2 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLK7|||http://purl.uniprot.org/uniprot/E9QNK5|||http://purl.uniprot.org/uniprot/Q3UQP0|||http://purl.uniprot.org/uniprot/Q5ERJ2|||http://purl.uniprot.org/uniprot/Q60748 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A N-glycosylation site within the signal peptide impedes its proper cleavage and function.|||Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Contains a disulfide bond in positions 45-70.|||G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels.|||Highly expressed in the heart. Also expressed in lungs, skeletal muscle, gastrointestinal tract, epididymis, and brain.|||Membrane|||Monomer. Interacts with CRF, UCN, UCN2 and UCN3 (By similarity).|||The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure (By similarity).|||The uncleaved pseudo signal peptide prevents receptor's oligomerization and coupling to G(i) subunits. It is also responsible for the rather low receptor localization at the plasma membrane (By similarity). http://togogenome.org/gene/10090:Osbp ^@ http://purl.uniprot.org/uniprot/Q3B7Z2 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OSBP family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer or homotrimer. Interacts (via FFAT motif) with VAPA. Interacts (via C-terminus) with RELCH (via the third HEAT repeat) (PubMed:29514919). Found in a complex composed of RELCH, OSBP1 and RAB11A (PubMed:29514919).|||Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.|||Probable cloning artifact.|||The FFAT motif is required for interaction with VATA and proper localization of the protein.|||The PH and the Ala/Gly-rich domains control cholesterol binding without affecting 25-hydroxycholesterol binding.|||The second coiled-coil domain is required for interaction with the tyrosine phosphatase.|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Gm21281 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or8b1 ^@ http://purl.uniprot.org/uniprot/K7N5P3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mapkap1 ^@ http://purl.uniprot.org/uniprot/Q8BKH7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All isoforms except isoform 4 can be incorporated into the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Interacts with ATF2, MAP3K2 and MAPK8. Interacts with GTP-bound HRAS and KRAS. Interacts with IFNAR2 and SGK1. Isoform 2 interacts with NBN. Isoform 1 interacts with CCDC28B.|||Belongs to the SIN1 family.|||Cell membrane|||Cytoplasmic vesicle|||Death during early embryonic stages.|||Nucleus|||Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is required for complex formation and mTORC2 kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription. Isoform 1 is involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex.|||Uniquitously expressed, with highest levels in testis, kidney and liver. Present in renal tubule cells (at protein level). http://togogenome.org/gene/10090:Hcst ^@ http://purl.uniprot.org/uniprot/Q9QUJ0 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DAP10 family.|||Homodimer; Disulfide-linked. Interacts with KLRK1 to form a stable complex, which results in surface expression of both proteins, whereas alone, it is minimally expressed. Interacts with PIK3R1 and GRB2. Interacts with CLEC5A (By similarity). Forms an CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP. Heterohexamer composed of four subunits of HCST/DAP10 and two subunits of KLRK1. Interacts (via transmembrane domain) with KLRK1 isoform 1 (via transmembrane domain); the interaction is required for KLRK1 cell surface expression on naive NK cells and activated CD8(+) T-cells, but is dispensable on activated TYROBP-expressing NK cells. Interacts (via transmembrane domain) with KLRK1 isoform 2 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induces NK cell-mediated cytotoxicity. Interacts with CD300H (By similarity).|||Immune reactivity to healthy cells that express KLRK1 ligands can happen under physiological conditions; NK cells are able to reject syngeneic bone marrow grafts when the bone marrow cells expressed sufficient KLRK1 ligand.|||Membrane|||Mice exhibit low expression of KLRK1 in NK cells, but no expression in resting T-cells. KLRK1 expression is not induced upon T-cell activation, while it is up-regulated in activated NK cells; NK cells promote KLRK1-mediated tumor rejection due to substitution of HCST by DAP12/TYROBP. Mice lacking HCST exhibit antitumor phenotype; they show enhanced immunity against melanoma malignancies due to hyperactive functioning of a group of T-cells that share properties of both T-cells and NK cells (NKT cells). NKT cells exhibit increased cytokine production and cytotoxicity, leading to efficient killing of melanoma tumors. Upon activation, T regulatory cells (Tregs) maintain higher levels of IL2 and produced significantly lower amounts of IL10 and IFN-gamma cytokines. NKT cells activated by IL2 efficiently lyse B16-melanoma tumors in vitro in an KLRK1-independent way; The hyperactivity of NKT cells in these mice is not related to signaling of KLRK1.|||O-glycosylated.|||Phosphorylated; PIK3R1 and GRB2 associate specifically with tyrosine-phosphorylated HCST.|||Transmembrane adapter protein which associates with KLRK1 to form an activation receptor KLRK1-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full KLRK1-HCST-mediated activation and ultimate killing of target cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity and enhances cytokine production initiated via DAP12/TYROBP-associated receptors. In T-cells, it provides primarily costimulation for TCR-induced signals. KLRK1-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells; indeed, melanoma cells that do not express KLRK1 ligands escape from immune surveillance mediated by NK cells. http://togogenome.org/gene/10090:Il1b ^@ http://purl.uniprot.org/uniprot/P10749 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-1 family.|||By LPS.|||Expressed in activated macrophages (at protein level).|||IL1B production occurs in 2 steps, each being controlled by different stimuli. First, inflammatory signals, such as LPS, stimulate the synthesis and promote the accumulation of cytosolic stores of pro-IL1B (priming). Then additional signals are required for inflammasome assembly, leading to CASP1 activation, pro-IL1B processing and eventually secretion of the active cytokine. IL1B processing and secretion are temporarily associated.|||Lysosome|||Monomer. Interacts with MEFV. Interacts with integrins ITGAV:ITGBV and ITGA5:ITGB1; integrin-binding is required for IL1B signaling. Interacts with cargo receptor TMED10; the interaction is direct and is required for the secretion of IL1B mature form (By similarity). Interacts with HSP90AB1; the interaction facilitates cargo translocation into the ERGIC (By similarity). Interacts with HSP90B1; the interaction facilitates cargo translocation into the ERGIC (By similarity).|||Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells. Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6. Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore.|||Secreted|||cytosol|||extracellular exosome http://togogenome.org/gene/10090:Gpatch11 ^@ http://purl.uniprot.org/uniprot/A0A0R4J215|||http://purl.uniprot.org/uniprot/Q3UFS4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the GPATCH11 family.|||kinetochore http://togogenome.org/gene/10090:Pfkm ^@ http://purl.uniprot.org/uniprot/P47857 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.|||Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E' sub-subfamily.|||Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.|||Cytoplasm|||GlcNAcylation decreases enzyme activity.|||Homo- and heterotetramers (By similarity). Phosphofructokinase (PFK) enzyme functions as a tetramer composed of different combinations of 3 types of subunits, called PFKM (M), PFKL (L) and PFKP (P). The composition of the PFK tetramer differs according to the tissue type it is present in. The kinetic and regulatory properties of the tetrameric enzyme are dependent on the subunit composition, hence can vary across tissues (Probable). Isoform 2 and isoform 3 interact (via N-terminal testis-specific region) with GSTM5. Isoform 2 and isoform 3 interact (via C-terminus) with HK1 (via N-terminal spermatogenic cell-specific region).|||Intron retention.|||Isoform 1 is expressed in skeletal muscle (at protein level). Isoform 2 and isoform 3 are testis-specific and are detected in quiescent sperm (at protein level). They are first detected in the cytoplasm of round spermatids and subsequently in the flagellum of elongated spermatids extending into the seminiferous tubule lumen (at protein level). Isoform 2 is expressed at higher level than isoform 3 in testis.|||Isoform 2 and isoform 3 are first seen on postnatal day 16 corresponding to the age when midpachytene spermatocytes are present in the synchronous first wave of spermatogenesis. Isoform 2 and isoform 3 levels increase substantially between days 14 and 18 and continue to increase to age 30 days of neonatal testis development.|||flagellum http://togogenome.org/gene/10090:Prpf6 ^@ http://purl.uniprot.org/uniprot/Q91YR7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Identified in the spliceosome B complex. Identified in the spliceosome C complex. Associates with the U5 snRNP particle. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, LSm proteins LSm2-8 and Sm proteins. Interacts with ARAF1. Interacts with AR and NR3C1, but not ESR1, independently of the presence of hormones. Interacts with USH1G.|||Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation.|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:Stau1 ^@ http://purl.uniprot.org/uniprot/Q9Z108 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds double-stranded RNA (regardless of the sequence) and tubulin. May play a role in specific positioning of mRNAs at given sites in the cell by cross-linking cytoskeletal and RNA components, and in stimulating their translation at the site.|||Binds tubulin. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Binds with low affinity single-stranded RNA or DNA homopolymers. Interacts with CASC3 in an RNA-dependent manner (By similarity).|||Cytoplasm|||One of the DRDB could be involved in RER binding.|||Rough endoplasmic reticulum|||The C-terminal contains the tubulin binding domain (TBD). http://togogenome.org/gene/10090:Pck2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0G0|||http://purl.uniprot.org/uniprot/Q8BH04 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.|||Binds 1 Mn(2+) ion per subunit.|||Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.|||In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one.|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Cplane1 ^@ http://purl.uniprot.org/uniprot/Q8CE72 ^@ Disease Annotation|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Intron sequences at both 5' and 3' ends.|||Defects in Jbts17 are the cause of the Hug (Heart under glass) phenotype which is a model of Joubert syndrome. Hug mice die prenatally and show skelatal dysplasia, craniofacial defects, polydactyly, cystic kidney, cerebellar hypoplasia and congenital heart defects of varying degrees. Most severely affected mutants die at mid-gestation with a transparent chest wall due to complete failure to form the rib cage. The phenotype is consistent with the spectrum of MKS-BBS-Joubert syndrome phenotypes.|||Interacts with FUZ; INTU and WDPCP; the interactors are proposed to form the core CPLANE (ciliogenesis and planar polarity effectors) complex (PubMed:27158779).|||Involved in ciliogenesis. Involved in the establishment of cell polarity required for directional cell migration (PubMed:25877302). Proposed to act in association with the CPLANE (ciliogenesis and planar polarity effectors) complex. Involved in recruitment of peripheral IFT-A proteins to basal bodies (PubMed:27158779).|||Membrane|||cilium http://togogenome.org/gene/10090:Or6c208 ^@ http://purl.uniprot.org/uniprot/Q8VFZ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cds1 ^@ http://purl.uniprot.org/uniprot/P98191 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDS family.|||Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (By similarity). Exhibits almost no acyl chain preference for PA, showing no discrimination for the sn-1/sn-2 acyl chain composition of PAs (By similarity). Plays an important role in regulating the growth of lipid droplets which are storage organelles at the center of lipid and energy homeostasis (PubMed:26946540). Positively regulates the differentiation and development of adipocytes (PubMed:26946540).|||Endoplasmic reticulum membrane|||Expressed in a structure probably corresponding to the thymic rudiment 12.5 dpc. No expression could be detected at earlier and later stages of embryonic development (10.5 dpc and 17.5 dpc).|||Expressed in adult brain, eye, smooth muscle and testis. Highly expressed in the inner segment of the photoreceptor layer of adult retina.|||Homodimer (By similarity). Interacts with FOS; this interaction may enhance catalytic activity (PubMed:22105363). http://togogenome.org/gene/10090:Ucma ^@ http://purl.uniprot.org/uniprot/Q14BU0 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the UCMA family.|||Expression inhibited by TGFB1, and weakly inhibited by BMP2.|||Golgi apparatus|||May be involved in the negative control of osteogenic differentiation of osteochondrogenic precursor cells in peripheral zones of fetal cartilage and at the cartilage-bone interface.|||Predominantly expressed in resting chondrocytes.|||Proteolytically cleaved by a furin-like convertase to generate a persistent C-terminal fragment found in almost the entire cartilage matrix, and affecting osteoblast differentiation.|||Secreted|||Sulfated on one or two tyrosine residues within the tryptic peptide 121-135.|||Transiently expressed in the developing mouse skeleton between day 13.5 dpc of embryonic development and 5 months of postnatal development. Absent in undifferentiated mesenchymal cells. Isoforms 1 and 3 are significantly increased with the onset of chondrogenesis, whereas Isoforms 2 and 4 are detected at a later stage.|||cytoskeleton|||extracellular matrix http://togogenome.org/gene/10090:Cenpb ^@ http://purl.uniprot.org/uniprot/P27790 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Antiparallel homodimer. Interacts with CENPT. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1.|||Interacts with centromeric heterochromatin in chromosomes and binds to a specific 17 bp subset of alphoid satellite DNA, called the CENP-B box. May organize arrays of centromere satellite DNA into a higher-order structure which then directs centromere formation and kinetochore assembly in mammalian chromosomes.|||N-terminally methylated by METTL11A/NTM1. Alpha-N-methylation is stimulated in response to extracellular stimuli, including increased cell density and heat shock, and seems to facilitate binding to CENP-B boxes. Chromatin-bound CENP-B is primarily trimethylated.|||Nucleus|||Poly-ADP-ribosylated by PARP1.|||centromere http://togogenome.org/gene/10090:Hsd17b8 ^@ http://purl.uniprot.org/uniprot/P50171 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.|||Kidney, liver, testis, ovary and spleen (PubMed:9712896, PubMed:15923359). Oviduct, uterus, mammary gland, vagina, prostate, clitoral gland and moderately heart, dorsal skin, brain and lung (PubMed:15923359).|||Mitochondrion matrix|||Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex, acts as scaffold protein, required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference, this enzymatic activity is not needed for the KAR function. Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+)(H). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters (By similarity). NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol. It efficiently catalyzes the oxidation of estradiol (E2), testosterone, and dihydrotestosterone. Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active estradiol (E2) (PubMed:9712896). http://togogenome.org/gene/10090:Ppa1 ^@ http://purl.uniprot.org/uniprot/Q4FK49|||http://purl.uniprot.org/uniprot/Q9D819 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPase family.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Tmem52b ^@ http://purl.uniprot.org/uniprot/Q0VBF2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Klf5 ^@ http://purl.uniprot.org/uniprot/Q9Z0Z7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Highest expression in digestive track.|||Interacts with WWP1. Interacts with ANP32B; this interaction induces promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcription factor that binds to GC box promoter elements. Activates the transcription of these genes.|||Ubiquitinated (By similarity). Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein. http://togogenome.org/gene/10090:Ifna14 ^@ http://purl.uniprot.org/uniprot/Q810G3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Matn4 ^@ http://purl.uniprot.org/uniprot/O89029 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with COMP.|||Lung, brain, sternum, kidney and heart.|||Major component of the extracellular matrix of cartilage.|||Secreted|||The short isoform was detected in 7 weeks old mice but not in developing mice (19.5 dpc embryos or in 2, 8, and 21 days old animals). http://togogenome.org/gene/10090:Cyp4f40 ^@ http://purl.uniprot.org/uniprot/G3UW81 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Trmo ^@ http://purl.uniprot.org/uniprot/Q562D6 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the tRNA methyltransferase O family.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||S-adenosyl-L-methionine-dependent methyltransferase responsible for the addition of the methyl group in the formation of N6-methyl-N6-threonylcarbamoyladenosine at position 37 (m(6)t(6)A37) of the tRNA anticodon loop of tRNA(Ser)(GCU). The methyl group of m(6)t(6)A37 may improve the efficiency of the tRNA decoding ability. May bind to tRNA. http://togogenome.org/gene/10090:Ifi47 ^@ http://purl.uniprot.org/uniprot/Q61635 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Or1e16 ^@ http://purl.uniprot.org/uniprot/Q8VGI1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. Activated by a lily-derived aldehyde as well as other odorants. May signal through an inositol 1,4,5-trisphosphate (IP3) second messenger system (By similarity).|||Olfactory epithelium. http://togogenome.org/gene/10090:Efs ^@ http://purl.uniprot.org/uniprot/Q64355 ^@ Domain|||Function|||PTM|||Similarity|||Tissue Specificity ^@ Belongs to the CAS family.|||Contains a central domain (substrate domain) containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL SH2 domains.|||Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. May serve as an activator of SRC and a downstream effector. Interacts with the SH3 domain of FYN and with CRK, SRC, and YES.|||Phosphorylated on multiple tyrosine residues. Phosphorylated on tyrosines by FYN and SRC.|||The SH3-binding sites that bind to the SRC SH3 domain are required for interaction with CRK and are implicated in promotion of serum response element (SRE) activation. The SH3 domain interacts with PTK2/FAK1.|||Widely expressed. Higher levels found in placenta and embryo. Lower levels found in brain, brainstem, muscle and lung. No expression in liver and intestine. http://togogenome.org/gene/10090:Clip2 ^@ http://purl.uniprot.org/uniprot/Q9Z0H8 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed at 10.5 dpc, expression declines until birth after which it suddenly increases. Expression gradually decreases until postnatal day 10, (the day when DLBs start to occur), then again increases and reaches the levels present in adult brain.|||Expressed in the brain, and very low levels in kidneys.|||Interacts with CLASP1 and CLASP2 (PubMed:11290329). Binds preferentially to tyrosinated microtubules, and only marginally to detyrosinated microtubules (PubMed:16954346).|||Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Mfsd4a ^@ http://purl.uniprot.org/uniprot/Q6PDC8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Membrane http://togogenome.org/gene/10090:Apba1 ^@ http://purl.uniprot.org/uniprot/B2RUJ5 ^@ Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Composed of an N-terminal domain that binds Munc18-1 and LIN-2/CASK, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane.|||Cytoplasm|||Golgi apparatus|||Isoform 3 is expressed in brain.|||Nucleus|||Part of a multimeric complex containing STXBP1 and STX1A. Interacts with STXBP1 (PubMed:21445306). Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (PubMed:10846156). Within the complex, interacts (via PDZ domain) with the motor protein KIF17; the interaction is direct and is required for association of KIF17 with the cargo that is to be transported (PubMed:10846156). Binds to the cytoplasmic domain of amyloid protein (APP) (By similarity). Interacts (via PDZ 1 and 2 domains) with FSPB (By similarity). Isoform 3 interacts (via its truncated PID domain) with active, GTP-bound RAB6A. Also interacts with GTP-bound RAB6B (By similarity).|||Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of AAP-beta (By similarity). Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (PubMed:10846156).|||The PID domain, truncated by 11 amino acids, as observed in isoform 3, but not full-length, mediates the interaction with RAB6A.|||The autoinhibitory helix linker occludes the APP binding site.|||This isoform interacts with RAB6 GTPases.|||perinuclear region http://togogenome.org/gene/10090:Exosc10 ^@ http://purl.uniprot.org/uniprot/P56960 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the RNA exosome complex. The catalytically inactive RNA exosome core (Exo-9) complex is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Interacts with C1D and MPHOSPH6 (By similarity). Interacts with ALYREF/THOC4 (By similarity). Interacts with MTREX; the interaction mediates the association of MTREX with nuclear RNA exosomes (By similarity). Interacts with DHX36; this interaction occurs in a RNase-insensitive manner (By similarity). Interacts with NRDE2 (By similarity).|||Cytoplasm|||Nucleus|||Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. EXOSC10 is required for nucleolar localization of C1D and probably mediates the association of MTREX, C1D and MPHOSPH6 with the RNA exosome involved in the maturation of 5.8S rRNA.|||nucleolus http://togogenome.org/gene/10090:Rabggta ^@ http://purl.uniprot.org/uniprot/Q9JHK4 ^@ Activity Regulation|||Disease Annotation|||Function|||Similarity|||Subunit ^@ Belongs to the protein prenyltransferase subunit alpha family.|||Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A.|||Defects in Rabggta are the cause of the gunmetal (gm) phenotype. Mice homozygous for gm have prolonged bleeding, thrombocytopenia and reduced platelet alpha- and delta-granule contents.|||Heterotrimer composed of RABGGTA, RABGGTB and CHM; within this trimer, RABGGTA and RABGGTB form the catalytic component B, while CHM (component A) mediates peptide substrate binding. The Rab GGTase dimer (RGGT) interacts with CHM (component A) prior to Rab protein binding; the association is stabilized by geranylgeranyl pyrophosphate (GGpp). The CHM:RGGT:Rab complex is destabilized by GGpp. Interacts with non-phosphorylated form of RAB8A; phosphorylation of RAB8A at 'Thr-72' disrupts this interaction.|||The enzymatic reaction requires the aid of a Rab escort protein (also called component A), such as CHM. http://togogenome.org/gene/10090:Sla2 ^@ http://purl.uniprot.org/uniprot/Q8R4L0 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Interacts (via its C-terminal domain) with CBL (phosphorylated). Interacts (via SH2 domain) with ZAP70 (phosphorylated) and CD3Z (phosphorylated). Interacts (via SH2 domain) with CSF1R (phosphorylated).|||Late endosome|||Mainly expressed in immune system. Highly expressed in spleen and thymus and expressed at intermediate levels in lung. Not expressed in liver, heart and brain. Isoform 1 is predominant in lung and spleen, while isoform 2 is predominant in thymus.|||Phosphorylated by CSF1R.|||PubMed:12024036 confirmed the alternative initiation by mutating the Met in position 1 to Val, and showed that isoform 1 is abolished in favor of isoform 2.|||The loss of the C-terminal domain partially abolishes the inhibitory function. http://togogenome.org/gene/10090:Timm29 ^@ http://purl.uniprot.org/uniprot/Q8BGX2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. The TIM22 complex forms a twin-pore translocase that uses the membrane potential as the external driving force. Required for the stability of the TIM22 complex and functions in the assembly of the TIMM22 protein into the TIM22 complex. May facilitate cooperation between TIM22 and TOM complexes by interacting with TOMM40.|||Component of the TIM22 complex, which core is composed of TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and TIMM29. Interacts with TIMM10B; the interaction is direct. Interacts with TOMM40; linking the TIM22 complex to the TOM complex. Interacts with TIMM22 (when oxidized); the interaction is direct.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Mocs2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J206|||http://purl.uniprot.org/uniprot/F6ZGI7|||http://purl.uniprot.org/uniprot/Q9Z223 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a sulfur carrier required for molybdopterin biosynthesis. Component of the molybdopterin synthase complex that catalyzes the conversion of precursor Z into molybdopterin by mediating the incorporation of 2 sulfur atoms into precursor Z to generate a dithiolene group. In the complex, serves as sulfur donor by being thiocarboxylated (-COSH) at its C-terminus by MOCS3. After interaction with MOCS2B, the sulfur is then transferred to precursor Z to form molybdopterin.|||Belongs to the MoaD family. MOCS2A subfamily.|||Belongs to the MoaE family. MOCS2B subfamily.|||C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-adenylated (-COAMP) via the hesA/moeB/thiF part of MOCS3, then thiocarboxylated (-COSH) via the rhodanese domain of MOCS3.|||Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin. Acts by mediating the incorporation of 2 sulfur atoms from thiocarboxylated MOCS2A into precursor Z to generate a dithiolene group.|||Heterotetramer; composed of 2 small (MOCS2A) and 2 large (MOCS2B) subunits.|||This protein is produced by a bicistronic gene which also produces the large subunit (MOCS2B) from an overlapping reading frame.|||This protein is produced by a bicistronic gene which also produces the small subunit (MOCS2A) from an overlapping reading frame.|||cytosol http://togogenome.org/gene/10090:Or4a77 ^@ http://purl.uniprot.org/uniprot/Q8VGM3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cib3 ^@ http://purl.uniprot.org/uniprot/Q0P523 ^@ Function|||Miscellaneous|||Subunit|||Tissue Specificity ^@ Acts as an auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells (PubMed:34089643). Plays a role in regulating hair cell MET channel localization and function (PubMed:34089643).|||Expressed in heart, liver and inner ear (PubMed:29255404). In the inner ear, expressed in vestibule and basilar membrane cells (PubMed:29255404). Expressed in megakaryocytes and endothelial cells.|||Monomer and homodimer (By similarity). Interacts with ITGA2B (via C-terminus cytoplasmic tail region); the interaction is stabilized/increased in a calcium and magnesium-dependent manner (PubMed:18989529). Interacts with TMC1 (PubMed:34089643).|||The binding of either calcium or magnesium significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form). http://togogenome.org/gene/10090:Atp6v1c2 ^@ http://purl.uniprot.org/uniprot/Q99L60 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase C subunit family.|||Predominantly expressed in the lung and kidney. Isoform 1 is lung-specific while isoform 3 is a kidney-specific isoform. Isoform 1 is localized in the lamellar bodies of type II alveolar cells. Isoform 2 is strongly expressed in the cortical and medulla collecting ducts and is found in the plasma membranes of renal alpha and beta intercalated cells.|||Significant expression seen at 17 dpc and not earlier.|||Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR. http://togogenome.org/gene/10090:Mybl2 ^@ http://purl.uniprot.org/uniprot/P48972 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2 (By similarity). Interacts with CCNF (via the Cyclin N-terminal domain) (By similarity).|||Nucleus|||Phosphorylated by cyclin A/CDK2 during S-phase. Phosphorylation at Thr-524 is probably involved in transcriptional activity (By similarity).|||Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene (By similarity). http://togogenome.org/gene/10090:Gjd3 ^@ http://purl.uniprot.org/uniprot/A0A654IET7|||http://purl.uniprot.org/uniprot/Q91YD1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family.|||Belongs to the connexin family. Delta-type subfamily.|||Cell membrane|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Ms4a6c ^@ http://purl.uniprot.org/uniprot/Q99N08 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MS4A family.|||Expressed only by thymus, spleen, peripheral lymph node and bone marrow.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Acod1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J027|||http://purl.uniprot.org/uniprot/P54987 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PrpD family.|||Cis-aconitate decarboxylase that catalyzes production of itaconate and is involved in the inhibition of the inflammatory response (PubMed:23609450, PubMed:23610393, PubMed:30635240, PubMed:31548418). Acts as a negative regulator of the Toll-like receptors (TLRs)-mediated inflammatory innate response by stimulating the tumor necrosis factor alpha-induced protein TNFAIP3 expression via reactive oxygen species (ROS) in LPS-tolerized macrophages (PubMed:23609450). Involved in antimicrobial response of innate immune cells; ACOD1-mediated itaconic acid production contributes to the antimicrobial activity of macrophages by generating itaconate, leading to alkylation of proteins, such as TFEB (PubMed:23610393, PubMed:35662396). Involved in antiviral response following infection by flavivirus in neurons: ACOD1-mediated itaconate production inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes (PubMed:30635240). Plays a role in the embryo implantation (PubMed:14500577).|||Expressed in LPS-tolerized macrophages (at protein level) (PubMed:23609450, PubMed:35662396). Expressed in the luminal epithelial cells of pregnant uterus (PubMed:14500577). Expressed in microglia and macrophage cells (PubMed:23609450, PubMed:35662396, PubMed:23610393).|||Homodimer.|||Mitochondrion|||Up-regulated after lipopolysaccharide (LPS) stimulation (PubMed:23609450, PubMed:23610393). Up-regulated in LPS-tolerized macrophage by LPS (PubMed:23609450, PubMed:23610393). Up-regulated synergistically by pro-inflammatory cytokines TNF and IFNG (PubMed:19014335). Up-regulated by pro-inflammatory cytokines IL1B and IFNB1 (PubMed:19014335). Up-regulated by progesterone and at the time of the embryo implantation (PubMed:14500577). Expression is activated by IRF1 in neurons in response to flavivirus infection in neurons (PubMed:30635240). http://togogenome.org/gene/10090:Mff ^@ http://purl.uniprot.org/uniprot/Q6PCP5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tango11 family.|||Homodimer (PubMed:30059978). Interacts with DNM1L (PubMed:30059978). Interacts with C11orf65/MFI; the interaction inhibits MFF interaction with DNM1L (PubMed:30059978).|||Mitochondrion outer membrane|||Peroxisome|||Plays a role in mitochondrial and peroxisomal fission (PubMed:23283981, PubMed:30059978). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface (PubMed:23283981). May be involved in regulation of synaptic vesicle membrane dynamics by recruitment of DNM1L to clathrin-containing vesicles (By similarity).|||synaptic vesicle http://togogenome.org/gene/10090:Arhgap18 ^@ http://purl.uniprot.org/uniprot/Q8K0Q5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with MPHOSPH6.|||Rho GTPase activating protein that suppresses F-actin polymerization by inhibiting Rho. Rho GTPase activating proteins act by converting Rho-type GTPases to an inactive GDP-bound state. Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts downstream of YAP1 and inhibits actin polymerization, which in turn reduces nuclear localization of YAP1. Regulates cell shape, spreading, and migration (By similarity).|||Widely expressed: expressed in most organs, except small intestine. http://togogenome.org/gene/10090:Noct ^@ http://purl.uniprot.org/uniprot/O35710 ^@ Caution|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCR4/nocturin family.|||Binds 2 magnesium ions, but the ions are only loosely bound to the protein.|||Cytoplasm|||Expression is highest in oocytes, begins to decrease after fertilization by the 4-cell stage and then slightly increases up to the blastocyst stage.|||Highly expressed in the differentiated adipocyte (at protein level). Ubiquitous.|||Immediate early gene (IEG) showing acute responses to several stimuli including serum shock, phorbol ester, lipopolysaccharide (LPS) and rosiglitazone, a PPARG agonist. Exhibits a high amplitude circadian rhythm with maximal levels in early evening. In constant darkness or constant light, the amplitude of the rhythm decreases. Expression is regulated by both light and food-entrained cues and by the CLOCK-BMAL1 heterodimer and PPARG. Up-regulated in cells undergoing adipogenesis.|||Interacts with PPARG.|||Mice exhibit metabolic defects including a resistance to diet-induced obesity, decreased fat storage, changes in lipid-related gene expression profiles in the liver, and altered glucose and insulin sensitivities. Exhibit a delayed early embryo development and at 12 weeks of age show enhanced skeletal mass and increased osteoblastogenesis.|||Mitochondrion|||Nucleus|||Phosphatase which catalyzes the conversion of NADP(+) to NAD(+) and of NADPH to NADH (By similarity). Shows a small preference for NADPH over NADP(+) (By similarity). Represses translation and promotes degradation of target mRNA molecules (By similarity). Plays an important role in post-transcriptional regulation of metabolic genes under circadian control (PubMed:20685873, PubMed:20498072). Exerts a rhythmic post-transcriptional control of genes necessary for metabolic functions including nutrient absorption, glucose/insulin sensitivity, lipid metabolism, adipogenesis, inflammation and osteogenesis (PubMed:20498072, PubMed:22082366, PubMed:21820310, PubMed:22073225, PubMed:22331129). Plays an important role in favoring adipogenesis over osteoblastogenesis and acts as a key regulator of the adipogenesis/osteogenesis balance (PubMed:20498072, PubMed:22082366). Promotes adipogenesis by facilitating PPARG nuclear translocation which activates its transcriptional activity (PubMed:20498072). Regulates circadian expression of NOS2 in the liver and negatively regulates the circadian expression of IGF1 in the bone (PubMed:22073225, PubMed:20685873). Critical for proper development of early embryos (PubMed:23449310).|||Was initially shown to have low deadenylase activity that was lost when the metal-binding Glu was mutated (PubMed:17400819). Later studies showed that the purified protein lacked deadenylase activity (PubMed:29860338). Was subsequently shown to act as a phosphatase (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Csta1 ^@ http://purl.uniprot.org/uniprot/B2RT71|||http://purl.uniprot.org/uniprot/P56567 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cystatin family.|||Cytoplasm|||This is an intracellular thiol proteinase inhibitor. http://togogenome.org/gene/10090:Svs6 ^@ http://purl.uniprot.org/uniprot/Q9D268 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SVP2/SVP5/SVP6 family.|||extracellular space http://togogenome.org/gene/10090:Trappc4 ^@ http://purl.uniprot.org/uniprot/Q544R8|||http://purl.uniprot.org/uniprot/Q9ES56 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAPP small subunits family.|||Belongs to the TRAPP small subunits family. TRAPPC4 subfamily.|||Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12 (By similarity). Interacts with SDC2 (PubMed:11018053).|||Core component of the TRAPP complexes which has a function of guanine nucleotide exchange factor activity for Rab1 GTPase. Plays a role in vesicular transport from endoplasmic reticulum to Golgi and autophagy (By similarity). May play a role in dendrite postsynaptic membrane trafficking (PubMed:11018053).|||Endoplasmic reticulum|||Golgi apparatus membrane|||Part of the multisubunit transport protein particle (TRAPP) complex.|||Postsynaptic cell membrane|||Vesicle|||Widely expressed.|||cis-Golgi network http://togogenome.org/gene/10090:Sdc3 ^@ http://purl.uniprot.org/uniprot/Q64519 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syndecan proteoglycan family.|||Cell membrane|||Cell surface proteoglycan that may bear heparan sulfate. May have a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism (By similarity).|||Interacts with TIAM1 (By similarity). Interacts with PTN (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment (By similarity). Interacts with MDK; this interaction induces SDC3 clustering; this interaction induces neuronal cell adhesion and neurite outgrowth (PubMed:12084985).|||O-glycosylated within the Thr/Ser-rich region which could interact with lectin domains on other molecules. http://togogenome.org/gene/10090:Zfp526 ^@ http://purl.uniprot.org/uniprot/Q8BI66 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus|||Partially unspliced pre-RNA. http://togogenome.org/gene/10090:Cars2 ^@ http://purl.uniprot.org/uniprot/Q8BYM8 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Binds 1 zinc ion per subunit.|||Mitochondrion matrix http://togogenome.org/gene/10090:Slc10a1 ^@ http://purl.uniprot.org/uniprot/A0A8V5KH54|||http://purl.uniprot.org/uniprot/O08705 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins (PubMed:10209268). It is strictly dependent on the extracellular presence of sodium (PubMed:10209268, PubMed:34060352). It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate (PubMed:10209268, PubMed:34060352). Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (By similarity).|||Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.|||Cell membrane|||Expressed in liver in higher amounts than isoform 2.|||Expressed in liver in lower amounts than isoform 1.|||Membrane http://togogenome.org/gene/10090:Gm20795 ^@ http://purl.uniprot.org/uniprot/J3QP49 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Csn1s2a ^@ http://purl.uniprot.org/uniprot/A0A0G2JET6|||http://purl.uniprot.org/uniprot/A0A0G2JGC6|||http://purl.uniprot.org/uniprot/Q02862|||http://purl.uniprot.org/uniprot/Q3TP41|||http://purl.uniprot.org/uniprot/Q547D1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-casein family.|||Important role in the capacity of milk to transport calcium phosphate.|||Mammary gland-specific. Secreted in milk.|||Secreted http://togogenome.org/gene/10090:Ptpn20 ^@ http://purl.uniprot.org/uniprot/O55082 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.|||Cytoplasm|||Detected between 2 and 3 weeks after birth, in parallel with the onset of meiosis.|||Nucleus|||Testis-specific. Specifically expressed in testicular germ cells that undergo meiosis (at protein level).|||Tyrosine-protein phosphatase targeted to sites of actin polymerization in response of varied extracellular stimuli. Has tyrosine phosphatase activity towards various tyrosyl phosphorylated substrates.|||centrosome http://togogenome.org/gene/10090:Xrcc4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J024|||http://purl.uniprot.org/uniprot/Q924T3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an activator of the phospholipid scramblase activity of XKR4 (PubMed:33725486). This form, which is generated upon caspase-3 (CASP3) cleavage, translocates into the cytoplasm and interacts with XKR4, thereby promoting phosphatidylserine scramblase activity of XKR4 and leading to phosphatidylserine exposure on apoptotic cell surface (PubMed:33725486).|||Belongs to the XRCC4-XLF family. XRCC4 subfamily.|||Chromosome|||Cytoplasm|||DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:9875844). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired. The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other. The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors. Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed. XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity. Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends. Promotes displacement of PNKP from processed strand break termini (By similarity).|||Homodimer and homotetramer in solution. Interacts with NHEJ1/XLF; the interaction is direct and is mediated via a head-to-head interaction between N-terminal head regions. Interacts with LIG4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry and XRCC4 is required for LIG4 stability. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Interacts with PRKDC; the interaction is direct. Interacts with XRCC6/Ku70; the interaction is direct. Interacts with APTX and APLF. Forms a heterotetramer with IFFO1; the interaction involves LIG4-free XRCC4 and leads to the relocalization of IFFO1 to the sites of DNA damage. Interacts with PNKP; mainly interacts with PNKP when phosphorylated at Thr-231, but is also able to interact at much lower level with PNKP when not unphosphorylated. Interacts with POLL (DNA polymerase lambda).|||Interacts with XKR4; interacts with the processed form of XKR4, which is cleaved by caspase.|||Mice show growth defects, premature senescence, IR sensitivity, and inability to support V(D)J recombination (PubMed:9875844). XRCC4 deficiency causes late embryonic lethality accompanied by defective lymphogenesis and defective neurogenesis manifested by extensive apoptotic death of newly generated postmitotic neuronal cells (PubMed:9875844).|||Nucleus|||Phosphorylated by PRKDC at the C-terminus in response to DNA damage; Ser-254 and Ser-312 constitute the main phosphorylation sites (PubMed:14599745). Phosphorylation by PRKDC at the C-terminus of XRCC4 and NHEJ1/XLF are highly redundant and regulate ability of the XRCC4-NHEJ1/XLF subcomplex to bridge DNA (By similarity). Phosphorylation by PRKDC does not prevent interaction with NHEJ1/XLF but disrupts ability to bridge DNA and promotes detachment from DNA (By similarity). Phosphorylation at Ser-319 and Ser-320 by PRKDC promotes recognition by the SCF(FBXW7) complex and subsequent ubiquitination via 'Lys-63'-linked ubiquitin (By similarity). Phosphorylation at Thr-231 by CK2 promotes interaction with PNKP; regulating PNKP activity and localization to DNA damage sites (By similarity). Phosphorylation by CK2 promotes interaction with APTX (By similarity).|||Ubiquitinated at Lys-290 by the SCF(FBXW7) complex via 'Lys-63'-linked ubiquitination, thereby promoting double-strand break repair: the SCF(FBXW7) complex specifically recognizes XRCC4 when phosphorylated at Ser-319 and Ser-320 by PRKDC, and 'Lys-63'-linked ubiquitination facilitates DNA non-homologous end joining (NHEJ) by enhancing association with XRCC5/Ku80 and XRCC6/Ku70. Monoubiquitinated.|||Undergoes proteolytic processing by caspase-3 (CASP3). This generates the protein XRCC4, C-terminus (XRCC4/C), which translocates to the cytoplasm and activates phospholipid scramblase activity of XKR4, thereby promoting phosphatidylserine exposure on apoptotic cell surface. http://togogenome.org/gene/10090:Zscan30 ^@ http://purl.uniprot.org/uniprot/Q149X8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Smarcd3 ^@ http://purl.uniprot.org/uniprot/Q6P9Z1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMARCD family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3 (By similarity). Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (By similarity). May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:22952240, PubMed:26601204). Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). Interacts with SMARCA4/BRG1/BAF190A. The precise distribution of the related SMARCD1, SMARCD2 and SMARCD3 proteins among these and other SWI/SNF nucleosome-remodeling complexes is not fully known. May allow recruitment of SWI/SNF containing complexes specifically to promoters where these factors are located. Also interacts with several nuclear receptors including PPARG/NR1C3, RXRA/NR1F1, ESR1, NR5A1, NR5A2/LRH1 and other transcriptional activators including the HLH protein SREBF1/SREBP1 and the homeobox protein PBX1 (By similarity). Interacts with PRDM1/BLIMP1 (By similarity).|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:22952240, PubMed:26601204). Stimulates nuclear receptor mediated transcription. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (PubMed:17640523).|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Socs2 ^@ http://purl.uniprot.org/uniprot/O35717 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subunit|||Tissue Specificity ^@ Expressed primarily in the testis, some expression in liver and lung.|||In the developing brain, expressed at relatively high levels from 10 dpc stages to young adulthood (P25) with peak levels from 14 dpc to P8. Levels of SOCS2 increase dramatically between 10 dpc and 12 dpc. At 12 dpc, high expression found in the olfactory epithelium with moderate expression in the neuroepithelium of the neocortex, presumptive striatum, hippocampus and septum. Low expression in the retina. At 14 dpc, in the cortical wall, levels increase in the cortical plate and decrease in the intermediate zone. High expression also in the hippocampus, fimbria, thalamic neuroepithelium and innermost layer of the retina. At P8, high expression in the neurons of the hippocampus. Lower levels found in the dentate gyrus. Levels of expression decrease between P8 and P15 and remain constant until P25. In adulthood, levels decrease. In the peripheral nervous system, expression found at low levels at 14 dpc in a subpopulation of neurons in the dorsal root ganglion.|||Interacts with IGF1R (By similarity). Associates with the Elongin BC complex (By similarity). Interacts with AREL1 and PRKCA (PubMed:31578312). Interacts with DCUN1D1 (By similarity).|||Mice deficient in SOCS2 exhibit considerable weight increase (30-40% more than normal) after 3 weeks of age. This is attributable to increase in visceral organ weight, carcass weight, long bone length and body length. In addition there is a thickening of the dermis due to excess collagen accumulation.|||Phosphorylation at Ser-52 by PKC facilitates its ubiquitination and proteasomal degradation.|||SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.|||Ubiquitinated; mediated by AREL1 and leading to its subsequent proteasomal degradation (PubMed:31578312). Ubiquitination is dependent on phosphorylation at Ser-52, by PKC and is stimulated by LPS (PubMed:31578312). http://togogenome.org/gene/10090:Dnaaf3 ^@ http://purl.uniprot.org/uniprot/Q3UYV8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DNAAF3 family.|||Cytoplasm|||Dynein axonemal particle|||Required for the assembly of axonemal inner and outer dynein arms. Involved in preassembly of dyneins into complexes before their transport into cilia (By similarity). http://togogenome.org/gene/10090:Defb45 ^@ http://purl.uniprot.org/uniprot/Q3V490 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Tafa2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0M7|||http://purl.uniprot.org/uniprot/Q3US64|||http://purl.uniprot.org/uniprot/Q7TPG7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TAFA family.|||Cytoplasm|||Expressed as early as 13.5 dpc, increases and peaks at 2 weeks after birth and is highly expressed until adulthood.|||Has a role as neurotrophic factor involved in neuronal survival and neurobiological functions.|||Mainly expressed in different brain regions, including cortex, amygdala and hippocampus (at protein level) (PubMed:30137205). Expressed by neurons and astrocytes (PubMed:30137205).|||Mutant mice grow and develop normally but exhibit impairments in spatial learning and memory and impairments in short- and long-term memory, accompanied with increased level of anxiety-like behaviors in open-field test. They also show decreased level of depression-like behaviors in forced-swim test and tail-suspension test (PubMed:30137205). They show neuronal loss, defects in dendritic and synaptic morphology, and apoptosis in the brain (PubMed:30137205).|||Nucleus http://togogenome.org/gene/10090:Atp5g2 ^@ http://purl.uniprot.org/uniprot/P56383 ^@ Disease Annotation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase C chain family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Interacts with DNAJC30; interaction is direct.|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. A homomeric c-ring of probably 10 subunits is part of the complex rotary element.|||Mitochondrion membrane|||There are three genes which encode the mitochondrial ATP synthase proteolipid and they specify precursors with different import sequences but identical mature proteins.|||This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).|||Trimethylated by ATPSCKMT at Lys-114. Methylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration. http://togogenome.org/gene/10090:H2al1d ^@ http://purl.uniprot.org/uniprot/Q5M8Q2 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical histone H2A which can replace conventional H2A in some nucleosomes and may play a role during spermatogenesis. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Belongs to the histone H2A family.|||Chromosome|||In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.|||Nucleus|||Strongly enriched in step 12-16 spermatids and accumulate during late spermiogenesis, in condensing spermatids (PubMed:17261847). Remains present in mature spermatozoa isolated from epididymis (PubMed:17261847). Rapidly disappears from the paternal pericentric heterochromatin regions after sperm-egg fusion (PubMed:18703863).|||Testis-specific.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules. Interacts with H2BC1/TH2B; preferentially dimerizes with H2BC1/TH2B to form nucleosomes (PubMed:17261847). http://togogenome.org/gene/10090:I830077J02Rik ^@ http://purl.uniprot.org/uniprot/Q3U7U4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Kdm4d ^@ http://purl.uniprot.org/uniprot/Q3U2K5 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the JHDM3 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys-9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.|||Nucleus http://togogenome.org/gene/10090:Mat2a ^@ http://purl.uniprot.org/uniprot/Q3THS6|||http://purl.uniprot.org/uniprot/Q99J57 ^@ Caution|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subunit ^@ According to a report, N6-methylation of MAT2A affects MAT2A mRNA stability instead of preventing splicing (PubMed:29262316). However, it was later shown that N6-methylation of MAT2A transcripts prevents recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production (By similarity).|||Belongs to the AdoMet synthase family.|||Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.|||Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.|||Catalyzes the formation of S-adenosylmethionine from methionine and ATP.|||Catalyzes the formation of S-adenosylmethionine from methionine and ATP. The reaction comprises two steps that are both catalyzed by the same enzyme: formation of S-adenosylmethionine (AdoMet) and triphosphate, and subsequent hydrolysis of the triphosphate.|||Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain. Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain.|||Protein expression is regulated by post-transcriptional regulation: in presence of S-adenosyl-L-methionine, METTL16 binds and methylates the first hairpin of the 3'-UTR region of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase. In S-adenosyl-L-methionine-limiting conditions, METTL16 binds the 3'-UTR region of MAT2A mRNA without methylating it due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A. http://togogenome.org/gene/10090:Mst1r ^@ http://purl.uniprot.org/uniprot/Q62190 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated in response to ligand binding on Tyr-1215 and Tyr-1216 in the kinase domain leading to further phosphorylation of Tyr-1330 and Tyr-1337 in the C-terminal multifunctional docking site.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Expressed in liver, skin, lung, brain, testis and kidney.|||Heterodimer of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2. Interacts when phosphorylated with downstream effectors including PIK3R1, PCLG1, GRB2 and GAB1. Interacts with integrin beta1/ITGB1 in a ligand-independent fashion. Isoform sf-Stk forms covalent heterodimers with friend spleen focus-forming virus (FSFFV) gp55.|||In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity.|||Interaction with FSFFV envelope-like membrane glycoprotein gp55 results in constitutive tyrosine phosphorylation and activation of isoform sf-Stk.|||Lacks part of the extracellular domain, oligomerizes and is constitutively activated. This isoform confers host susceptibility to Friend disease.|||Membrane|||Mice show increased inflammation in an IFN-gamma-mediated delayed-type hypersensitivity reaction and increased susceptibility to lipopolysaccharide-induced endotoxic shock.|||O-mannosylation of IPT/TIG domains on Thr or Ser residues by TMEM260 is required for protein maturation. O-mannosylated residues are composed of single mannose glycans that are not elongated or modified.|||Proteolytic processing yields the two subunits.|||Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.|||Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Cse1l ^@ http://purl.uniprot.org/uniprot/Q9ERK4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the XPO2/CSE1 family.|||Complete embryonic lethality at around 5.5 dpc.|||Cytoplasm|||Export receptor for importin-alpha. Mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates (cargos) have been released into the nucleoplasm. In the nucleus binds cooperatively to importin-alpha and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the importin-alpha from the export receptor. CSE1L/XPO2 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.|||Found in a complex with CSE1L/XPO2, Ran and KPNA2. Binds with high affinity to importin-alpha only in the presence of RanGTP. The complex is dissociated by the combined action of RanBP1 and RanGAP1. Interacts with CFTR.|||Nucleus|||Ubiquitous. Detected in embryos from 5 to 17 dpc. Highly expressed in adult testis, heart, brain, lung, liver, skeletal muscle, spleen and kidney. http://togogenome.org/gene/10090:Dapk1 ^@ http://purl.uniprot.org/uniprot/Q80YE7 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+)/calmodulin. Regulated by a locking mechanism, involving autophosphorylation at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.|||Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3 (By similarity). Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.|||High levels in bladder, uterus, vas deferens, lung, liver and kidney.|||In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can cause dephosphorylation at Ser-308.|||Interacts with KLHL20 (By similarity). Interacts (via death domain) with MAPK1 and MAPK3 (By similarity). Interacts with MAP1B (via N-terminus) (By similarity). Interacts with PRKD1 in an oxidative stress-regulated manner (By similarity). Interacts with PIN1, PDCD6, BECN1, TSC2 and STX1A (By similarity). Interacts (via kinase domain) with DAPK3 (via kinase domain) (By similarity). Interacts with GRINB (PubMed:20141836). Interacts (via death domain) with UNC5B (via death domain) (PubMed:15729359). Interacts with UNC5C (via death domain) (By similarity).|||Mice are protected against cerebral ischemic neuronal death.|||The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.|||Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Insm1 ^@ http://purl.uniprot.org/uniprot/Q05BD7|||http://purl.uniprot.org/uniprot/Q63ZV0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the INSM1 family.|||Expressed in adrenal gland. Expressed in the dentate gyrus of the hippocampus and the wall of the lateral ventricle. Expressed in pancreatic and intestinal endocrine cells.|||Expressed in differentiating endocrine cells of the anterior pituitary gland between 11.5 and 17.5 dpc. Expressed in all hormone-secreting cell types of the pituitary gland. Expressed in primary sympathetic ganglion chain, spinal cord and in neurons of the dorsal root ganglia at 9.5 dpc. Expressed in chromaffin cells of the adrenal medulla at 13.5 dpc (at protein level). Expressed in the developing central nervous system (CNS). Expressed in midbrain-hindbrain region at 9.5 dpc, in the spinal cord and telencephalon at 11 dpc. Expressed in the forebrain, midbrain, hind brain, spinal cord, cerebellum, olfactory bulb and retina between 11.5 and 14.5 dpc. Expressed in neural stem and progenitor cells of the developing neocortex in both the ventricular zone (VZ) and in the adjacent subventricular zone (SVZ), and in the external granule cell layer of the developing cerebellum between 11 and 16.5 dpc. Expressed in neural progenitor cells at the apical side of the VZ, collectively referred to as apical basal cells (APs; neuroepithelial cells, radial glial cells and short neural precursors) between 10.5 and 16.5 dpc. Expressed in neural progenitor cells in the basal region of the VZ between 10.5 and 16.5 dpc and at later stages in basal progenitor cells (BPs) of the SVZ. Expressed in the cerebellum and pineal gland at 18.5 dpc. Expressed in islet progenitor cells at 10.5 dpc. Expressed in endocrine pancreatic cells, enteric nervous system, duodenum, stomach, thymus, thyroid, adrenal glands at 15.5 dpc.|||Interacts (via the N-terminal region) with CCND1 (via cyclin N-terminal domain); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and increases its transcriptional repressor activity. Interacts with HDAC3; the interaction increases its transcriptional repressor activity (By similarity). Interacts (via the SNAG domain) with HDAC1. Interacts (via the SNAG domain) with HDAC2. Interacts (via the SNAG domain) with KDM1A. Interacts (via the SNAG domain) with RCOR1. Interacts with SORBS1.|||Mice die during the second half of gestation; lethality is caused by heart failure due to insufficient catecholamine synthesis. Display pancreatic, intestinal and sympatho-adrenal endocrine cell development impairment. Exhibits fewer terminally dividing neuronogenic basal progenitor cells (BPs) in the neocortex.|||Nucleus|||Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle-specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (By similarity). Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation.|||The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity. http://togogenome.org/gene/10090:Epas1 ^@ http://purl.uniprot.org/uniprot/P97481 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in most tissues, with highest levels in lung, followed by heart, kidney, brain and liver. Predominantly expressed in endothelial cells. Also found in smooth muscle cells of the uterus, neurons, and brown adipose tissue. High expression in embryonic choroid plexus and kidney glomeruli.|||In day 11 embryo, expression is almost exclusively seen in endothelial cells of the intersegmental blood vessels separating the somites, the atrial and ventricular chambers of the heart, and the dorsal aorta. High expression also occurs in extraembryonic membranes. In the developing brain of day 13 embryo, endothelial cells of the highly vascularized choroid plexus contain high levels of EPAS1.|||In normoxia, is hydroxylated on Asn-851 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.|||In normoxia, is probably hydroxylated on Pro-405 and Pro-530 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity).|||Interacts with HIF3A isoform 2 (PubMed:21546903). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Interacts with CREBBP (PubMed:11983697). Interacts with EGLN1. Interacts with VHL (By similarity).|||Nucleus|||Nucleus speckle|||Phosphorylated on multiple sites in the CTAD.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.|||Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD (By similarity). http://togogenome.org/gene/10090:Snrpd2 ^@ http://purl.uniprot.org/uniprot/P62317|||http://purl.uniprot.org/uniprot/Q14AF6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP core protein family.|||Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Component of the minor spliceosome, which splices U12-type introns. Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly. Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP.Interacts with SMN1; the interaction is direct. Interacts with GEMIN2; the interaction is direct. Interacts with SNRPD1; the interaction is direct. Interacts with SNRPF; the interaction is direct.|||Nucleus|||Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.|||cytosol http://togogenome.org/gene/10090:Amz1 ^@ http://purl.uniprot.org/uniprot/A1L312|||http://purl.uniprot.org/uniprot/Q8BVF9 ^@ Cofactor|||Function|||Similarity ^@ Belongs to the peptidase M54 family.|||Binds 2 Zn(2+) ions per subunit. One is catalytic, whereas the other seems to have a structural role.|||Probable zinc metalloprotease. http://togogenome.org/gene/10090:Prl2c1 ^@ http://purl.uniprot.org/uniprot/Q5SVM0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Rin3 ^@ http://purl.uniprot.org/uniprot/P59729|||http://purl.uniprot.org/uniprot/Q3U332 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RIN (Ras interaction/interference) family.|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Interacts with CD2AP, RAB5B, RAB31 and BIN1.|||Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function (By similarity). http://togogenome.org/gene/10090:Hebp2 ^@ http://purl.uniprot.org/uniprot/Q9WU63 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HEBP family.|||Can promote mitochondrial permeability transition and facilitate necrotic cell death under different types of stress conditions (By similarity). May have low affinity for heme (PubMed:15518569).|||Cytoplasm|||Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel.|||Has been described as heme-binding protein (PubMed:15518569) in mouse, but the human protein does not bind hemin. His-42, a residue essential for heme binding in mouse, is not conserved in all orthologs, or in the heme-binding family member HEBP1.|||Mitochondrion|||Monomer. Interacts with LRPPRC. May interact with BCL2L1; an interaction with BCL2L1 was observed using a peptide, but not with the full-length protein. The full-length protein would have to undergo a major conformation change for the interaction to occur. Interacts with PDCD6. http://togogenome.org/gene/10090:Sftpb ^@ http://purl.uniprot.org/uniprot/P50405 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked.|||Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).|||Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of palmitic acid to nearly 70 millinewtons per meter.|||surface film http://togogenome.org/gene/10090:Acyp2 ^@ http://purl.uniprot.org/uniprot/P56375 ^@ Similarity ^@ Belongs to the acylphosphatase family. http://togogenome.org/gene/10090:H2-Q6 ^@ http://purl.uniprot.org/uniprot/P79568 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Stx8 ^@ http://purl.uniprot.org/uniprot/O88983 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Forms a SNARE complex with STX7, VTI1B and VAMP8 which functions in the homotypic fusion of late endosomes. Part of the SNARE core complex containing STX7, VAMP8 and VTI1B. Interacts with VAMP8 (By similarity). Interacts with HECTD3. Interacts with TPC1 (PubMed:28855648).|||Membrane|||Ubiquitinated by HECTD3.|||Vesicle trafficking protein that functions in the early secretory pathway, possibly by mediating retrograde transport from cis-Golgi membranes to the ER. http://togogenome.org/gene/10090:S1pr3 ^@ http://purl.uniprot.org/uniprot/Q9Z0U9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Most abundant in heart, lung, kidney and spleen; low but detectable in brain, thymus, muscle and testis; and nearly undetectable in liver, stomach, and intestine. Expressed in embryonic lung from embryonic day 14-18. Also abundantly detected in embryonic nasal cartilage, sphenoid bone, vena cava, Meckel's cartilage/incisor teeth, genital tubercle and bladder.|||Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. http://togogenome.org/gene/10090:Or5af2 ^@ http://purl.uniprot.org/uniprot/Q5NC55 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccdc120 ^@ http://purl.uniprot.org/uniprot/A2AEV7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells (PubMed:28422092). Together with CCDC68, cooperate with subdistal appendage components ODF2, NIN and CEP170 for hierarchical subdistal appendage assembly (PubMed:28422092). Recruits NIN and CEP170 to centrosomes (PubMed:28422092). Also required for neurite growth (By similarity). Localizes CYTH2 to vesicles to allow its transport along neurites, and subsequent ARF6 activation and neurite growth (By similarity).|||Cytoplasm|||Endosome|||Interacts with NIN and CEP170; leading to recruit them to centrosomes (By similarity). Interacts with CYTH2; this interaction is direct and stabilizes CCDC120, possibly by preventing ubiquitination (By similarity).|||Ubiquitinated; interaction with CYTH2 may prevent ubiquitination.|||centriole|||growth cone|||neuron projection http://togogenome.org/gene/10090:Kif13a ^@ http://purl.uniprot.org/uniprot/F8VQ75 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. http://togogenome.org/gene/10090:Or52h9 ^@ http://purl.uniprot.org/uniprot/Q8VG78 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mpz ^@ http://purl.uniprot.org/uniprot/A0A5F8MPM4|||http://purl.uniprot.org/uniprot/E9QK82|||http://purl.uniprot.org/uniprot/P27573 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the myelin P0 protein family.|||Cell membrane|||Expressed in the sciatic nerves at postnatal days P6 to P12.|||Found only in peripheral nervous system Schwann cells.|||Homodimer and homotetramer.|||Is an adhesion molecule necessary for normal myelination in the peripheral nervous system. It mediates adhesion between adjacent myelin wraps and ultimately drives myelin compaction.|||Membrane|||N-glycosylated; contains sulfate-substituted glycan. http://togogenome.org/gene/10090:Idh2 ^@ http://purl.uniprot.org/uniprot/P54071 ^@ Cofactor|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-413 dramatically reduces catalytic activity. Deacetylated by SIRT3 (By similarity).|||Belongs to the isocitrate and isopropylmalate dehydrogenases family.|||Binds 1 Mg(2+) or Mn(2+) ion per subunit.|||By oxidative stress (at protein level).|||Homodimer.|||Mitochondrion|||Plays a role in intermediary metabolism and energy production (PubMed:8867815). It may tightly associate or interact with the pyruvate dehydrogenase complex (PubMed:8867815).|||Predominantly expressed in heart, liver and kidney (PubMed:8867815, PubMed:11278619). Expressed in activated B lymphocytes (PubMed:8867815).|||Up-regulated in activated B lymphocytes. http://togogenome.org/gene/10090:Dgkb ^@ http://purl.uniprot.org/uniprot/Q6NS52 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by calcium.|||Belongs to the eukaryotic diacylglycerol kinase family.|||Cell membrane|||Cytoplasm|||Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:20657643). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable). Has a higher activity with long-chain diacylglycerols like 1,2-di-(9Z-octadecenoyl)-sn-glycerol compared to 1,2-didecanoyl-sn-glycerol (By similarity). Specifically expressed in brain, it regulates neuron-specific morphological changes including neurite branching and neurite spine formation (PubMed:20657643).|||Expressed in hippocampus, cerebral cortex, and caudate putamen (at protein level).|||Homozygous knockout mice are viable and fertile with no significant difference in weight (PubMed:20657643). However, long-term potentiation (LTP) and cognitive functions including spatial and long-term memory are affected in these mice (PubMed:20657643). A decrease in the total length of neurites and branches together with a reduced number of neurite spines are observed (PubMed:20657643).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Kirrel2 ^@ http://purl.uniprot.org/uniprot/Q7TSU7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily.|||Cell membrane|||Highly expressed in beta-cells of the pancreatic islets. Expression is seen in podocytes of kidney glomeruli, and in the cerebellum and hindbrain at 12.5 dpc, in the spinal cord at 10.5 dpc, and in retina and hypothalamus at 13.5 dpc.|||Homodimer (PubMed:26324709). Interacts with NPHS2/podocin (via the C-terminus). Interacts with NPHS1 (via the Ig-like domains). Interacts with FYN (PubMed:26324709).|||May regulate basal insulin secretion.|||N-glycosylated.|||No visible phenotype. However basal insulin secretion is modestly increased in pancreatic islets of KIRREL2 deficient mice.|||Phosphorylated at Ser-548 or Ser-549; due to site ambiguity, the exact position of the serine phosphorylation could not be determined. Phosphorylation at residues Tyr-631 and/or Tyr-632. FYN mediates tyrosine phosphorylation in pancreatic beta-cells.|||The extracellular domain is cleaved leading to the generation of a soluble fragment and a membrane-bound C-terminal fragment, which is further cleaved by gamma-secretase. http://togogenome.org/gene/10090:Stac ^@ http://purl.uniprot.org/uniprot/P97306|||http://purl.uniprot.org/uniprot/Q3UPL9|||http://purl.uniprot.org/uniprot/Q3UYD4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed predominantly in brain (PubMed:8954993, PubMed:23818578) Detected in brain neurons, more specifically in hippocampus, cerebellum and inferior olive (PubMed:8954993). Highly expressed in urinary bladder, and detected at lower levels in adrenal gland (PubMed:23818578). Detected at very low levels in heart, liver, lung and kidney (PubMed:8954993).|||Expression in brain started at late 13.5 dpc and continued to adult (8W) with a peak around P10.|||Interacts (via SH3 domains) with CACNA1S (PubMed:29467163). Interacts with CACNA1H (PubMed:27149520). Interacts with CACNA1C (Probable) (PubMed:29363593).|||Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity (PubMed:27149520). Plays a minor and redundant role in promoting the expression of calcium channel CACNA1S at the cell membrane, and thereby contributes to increased channel activity (PubMed:29467163). Slows the rate of calcium-mediated inactivation of CACNA1C calcium channel activity (PubMed:29363593).|||cytosol|||sarcolemma http://togogenome.org/gene/10090:Npm2 ^@ http://purl.uniprot.org/uniprot/Q80W85 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleoplasmin family.|||Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development. Probably involved in sperm DNA decondensation during fertilization.|||Homopentamer, when bound to H2A-H2B dimers only. Homodecamer of two stacked pentamers, when bound to H2A-H2B dimers and H3-H4 tetramers simultaneously (By similarity).|||Nucleus|||Ovary specific.|||The acidic tract A2 mediates histone binding. http://togogenome.org/gene/10090:Actn3 ^@ http://purl.uniprot.org/uniprot/O88990 ^@ Function|||Similarity|||Subunit ^@ Belongs to the alpha-actinin family.|||F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (By similarity).|||Homodimer; antiparallel. Also forms heterodimers with ACTN2. Interacts with MYOZ1 (By similarity). http://togogenome.org/gene/10090:Slfn1 ^@ http://purl.uniprot.org/uniprot/Q9Z0I7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Schlafen family.|||Cytoplasm|||Interacts with DNAJB6; promoting nuclear translocation and ability to promote cell-cycle arrest.|||Mainly expressed in the thymus, lymph node and spleen (PubMed:9846487). Specifically expressed in T-lineage cells, but not in B-cells (PubMed:9846487). Strongly up-regulated during the differentiation from CD4(+)CD8(+) double-positive (DP) to CD4(+) or CD8(+) single-positive (SP) thymocytes (PubMed:9846487). Highly expressed in quiescent single-positive thymocytes and T-cells (PubMed:9846487). The expression substantially decreases after TCR (T-cell receptor)-mediated activation (PubMed:9846487).|||No visible phenotype.|||Nucleus|||Protein expressed in resting T-cells, which is required for maintaining T-cells in the quiescent state (PubMed:9846487, PubMed:15946944, PubMed:18373498). Acts by promoting cell-cycle arrest of T-cells through inhibiting the expression of cyclin-D1 (CCND1) (PubMed:15946944). http://togogenome.org/gene/10090:Oprl1 ^@ http://purl.uniprot.org/uniprot/A0A5F8MPZ9|||http://purl.uniprot.org/uniprot/B0R0C0|||http://purl.uniprot.org/uniprot/P35377|||http://purl.uniprot.org/uniprot/Q542U1 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasmic vesicle|||G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.|||In the brain, isoform KOR3 and isoform KOR3C are most abundant in hypothalamus and periaqueductal gray. Isoform KOR3A is highly expressed in cortex, striatum and brainstem. Isoform KOR3D is highly expressed in cerebellum, hypothalamus and brainstem. Detected in spleen lymphocytes.|||Membrane|||Mutant mice do not show altered basal nociception, but are no longer susceptible to modulation of nociception by the neuropeptide nociceptin. Contrary to wild-type, they do not show reduced locomotion in response to the neuropeptide nociceptin. In addition, mutant mice show subtle hearing defects.|||Phosphorylation at Ser-360 requires GRK3.|||Vesicle http://togogenome.org/gene/10090:Map2k1 ^@ http://purl.uniprot.org/uniprot/P31938|||http://purl.uniprot.org/uniprot/Q3TMJ8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Affects fibroblast shape and impairs haptotaxis and adhesion-dependent ERK-signaling.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.|||Cytoplasm|||Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (By similarity). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.|||Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14 (By similarity). Forms a heterodimer with MAP2K2/MEK2 (PubMed:19219045). Forms heterodimers with KSR2 which further dimerize to form tetramers (By similarity). Interacts with KSR1 or KSR2 and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF or KSR2-BRAF dimerization (By similarity). Interacts with ARBB2, LAMTOR3, MAPK1/ERK2 and RAF1 (By similarity). Interacts with MAPK1/ERK2 (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with PPARG (By similarity). Interacts with SGK1 (By similarity). Interacts with BIRC6/bruce (By similarity). Interacts with KAT7; the interaction promotes KAT7 phosphorylation (PubMed:23319590). Interacts with RAF1 and NEK10; the interaction is required for ERK1/2-signaling pathway activation in response to UV irradiation (By similarity). Interacts with TRAF3IP3 (By similarity).|||Membrane|||Nucleus|||Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity (PubMed:8385802). Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK (PubMed:19219045). MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK (PubMed:19219045). Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation (By similarity).|||Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222 (By similarity). MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (By similarity). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By similarity). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity).|||The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1.|||centrosome|||spindle pole body http://togogenome.org/gene/10090:Ctxn3 ^@ http://purl.uniprot.org/uniprot/Q8BXZ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the cortexin family.|||Membrane http://togogenome.org/gene/10090:Cps1 ^@ http://purl.uniprot.org/uniprot/Q8C196 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with P.berghei (ANKA strain) phospholipid scramblase PLSCR; the interaction is involved in the interaction between parasite sporozoites and host hepatocytes.|||Acetylation of Lys-287, Lys-603, Lys-841 and Lys-1291 is observed in liver mitochondria from fasted mice but not from fed mice.|||Can form homooligomers (monomers as predominant form and dimers).|||Cell membrane|||Expressed in hepatocytes (at protein level).|||Glutarylated. Glutarylation levels increase during fasting. Deglutarylated by SIRT5 at Lys-55, Lys-219, Lys-412, Lys-889, Lys-892, Lys-915, Lys-1360 and Lys-1486, leading to activation.|||Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.|||Mitochondrion|||Requires N-acetyl-L-glutamate (NAG) as an allosteric activator.|||Succinylated at Lys-44, Lys-287 and Lys-1291. Desuccinylated at Lys-1291 by SIRT5, leading to activation.|||The type-1 glutamine amidotransferase domain is defective.|||Undergoes proteolytic cleavage in the C-terminal region corresponding to the loss of approximately 12 AA residues from the C-terminus.|||Was initially reported to be deacetylated by Sirt5 (PubMed:19410549). However, it was later shown that Sirt5 has poor deacetylase activity and mediates desuccinylation of Cps1 instead (PubMed:22076378).|||nucleolus http://togogenome.org/gene/10090:Defa17 ^@ http://purl.uniprot.org/uniprot/P28310 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-defensin family.|||Paneth cells of the small bowel.|||Probably contributes to the antimicrobial barrier function of the small bowel mucosa.|||Secreted http://togogenome.org/gene/10090:Abracl ^@ http://purl.uniprot.org/uniprot/E9QMV2|||http://purl.uniprot.org/uniprot/Q4KML4 ^@ Similarity ^@ Belongs to the costars family. http://togogenome.org/gene/10090:Aen ^@ http://purl.uniprot.org/uniprot/Q9CZI9 ^@ Function|||Subcellular Location Annotation ^@ Exonuclease with activity against single- and double-stranded DNA and RNA. Mediates p53-induced apoptosis. When induced by p53 following DNA damage, digests double-stranded DNA to form single-stranded DNA and amplifies DNA damage signals, leading to enhancement of apoptosis (By similarity).|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Or12j3 ^@ http://purl.uniprot.org/uniprot/Q8VFE8 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Lcn8 ^@ http://purl.uniprot.org/uniprot/Q924P3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||May play a role in male fertility. May act as a retinoid carrier protein within the epididymis.|||Predominantly expressed in epididymis.|||Secreted http://togogenome.org/gene/10090:Vmn1r211 ^@ http://purl.uniprot.org/uniprot/Q8R266 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plxnb2 ^@ http://purl.uniprot.org/uniprot/B2RXS4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling (PubMed:17554007). Plays a role in glutamatergic synapse development and is required for SEMA4A-mediated excitatory synapse development (PubMed:29981480). Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248' (PubMed:17554007). Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development (PubMed:19948886). Regulates the migration of cerebellar granule cells in the developing brain (PubMed:21122816). Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton (By similarity). Plays a role in axon guidance, invasive growth and cell migration (By similarity). May modulate the activity of RAC1 and CDC42 (PubMed:21966369). Down-regulates macrophage migration in wound-healing assays (in vitro) (PubMed:21966369).|||Detected in macrophages from spleen and bone marrow (at protein level) (PubMed:21966369). Detected in granule cells in the developing cerebellum, dentate gyrus and olfactory bulb (PubMed:17554007). Expressed in neurons and glia in the developing hippocampus (PubMed:29981480).|||Embryonic and perinatal lethality, due to defects in brain and neural tube development. Mice exhibit abnormal cortical layering and defective migration and differentiation of several subtypes of cortical neurons. Cranial neural folds fail to converge in most embryos, leading to an open neural tube and exencephaly. Likewise, mice exhibit defects in the embryonic development of the cerebellum and the olfactory bulb.|||Monomer, and heterodimer with PLXNB1 (By similarity). Interacts with MET, ARHGEF11 and ARHGEF12 (By similarity). May also interact with MST1R (By similarity). Interacts with SEMA4C (PubMed:17554007, PubMed:21122816). Interacts with SEMA4D (PubMed:17554007). Interacts with SEMA4G (PubMed:21122816). http://togogenome.org/gene/10090:Dnd1 ^@ http://purl.uniprot.org/uniprot/Q6VY05 ^@ Developmental Stage|||Disease Annotation|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Defects in Dnd1 are the cause of the Ter mutation phenotype. Ter mice are characterized by primordial germ cell loss and susceptibility to spontaneous testicular germ cell tumors (TGCT). They are sterile, but viable. Isoform 1 defects may be the cause of tumor development.|||Interacts with APOBEC3.|||Isoform 1 and isoform 2 are expressed in testis. Isoform 1 is expressed continuously in post natal (PN) testis although levels are low between PN1 to PN6. Isoform 2 is expressed from PN 20 onwards. Isoform 2 is strongly expressed in meiotic and in post-meiotic germ cells of the testis with highest expression at the elongated spermatid stage (at protein level). Expressed in testis and heart. Expressed in germ cells and genital ridges. Not detected in testicular tumors.|||Isoform 1, but not isoform 2, is expressed in embryos at 13.5 and 15.5 dpc. Isoform 1, but not isoform 2, is expressed in primordial gonads at 13.5 and 15.5 dpc. Isoform 1, but not isoform 2, is expressed in ES cell lines. Isoform 1, but not isoform 2, is expressed in embryonic germ (EG) cells (at protein level). Detected in the embryo and allantoic bud at 7.5 dpc, in the neuroectoderm at 8.5 dpc, and widespread at 9.5 dpc, including the neural tube, head mesenchyme, first branchial arch and the hindgut, through which primordial germ cells are migrating. At 11.5 dpc, also expressed in the XY and XX genital ridges. Expressed in genital ridges at 13.5 dpc. Between 12.5 to 14.5 dpc, up-regulated in the testis cords of the XY gonads and down-regulated in XX gonads. Down-regulation occurs progressively as an anterior to posterior wave.|||May be due to intron retention.|||Nucleus|||RNA-binding factor that positively regulates gene expression by prohibiting miRNA-mediated gene suppression (By similarity). Relieves miRNA repression in germline cells (By similarity). Prohibits the function of several miRNAs by blocking the accessibility of target mRNAs (By similarity). Sequence-specific RNA-binding factor that binds specifically to U-rich regions (URRs) in the 3' untranslated region (3'-UTR) of several mRNAs (By similarity). Does not bind to miRNAs (By similarity). Isoform 1 may play a role during primordial germ cell (PGC) survival. However, does not seem to be essential for PGC migration. http://togogenome.org/gene/10090:Ncan ^@ http://purl.uniprot.org/uniprot/A0A0R4IZX5|||http://purl.uniprot.org/uniprot/P55066 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the aggrecan/versican proteoglycan family.|||Brain.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May modulate neuronal adhesion and neurite growth during development by binding to neural cell adhesion molecules (NG-CAM and N-CAM). Chondroitin sulfate proteoglycan; binds to hyaluronic acid.|||O-glycosylated; contains chondroitin sulfate.|||Secreted http://togogenome.org/gene/10090:Gm20932 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Ogfod3 ^@ http://purl.uniprot.org/uniprot/Q9D136 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the OGFOD3 family.|||Binds 1 Fe(2+) ion per subunit.|||Membrane http://togogenome.org/gene/10090:Ascl3 ^@ http://purl.uniprot.org/uniprot/Q9JJR7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein.|||Expressed in the salivary duct cells (PubMed:11784080, PubMed:18572159). Also expressed at lower levels in testis and epididymis (PubMed:11784080). Expressed in the olfactory epithelium (OE), in a subset of apical microvillar cells (PubMed:27910949).|||Expressed throughout embryonic development at 12.5, 14.5, 16.5 and 18.5 days post coitum (dpc), in cells localized at the apical region of the developing olfactory epithelium (OE) (PubMed:27910949). Expressed transiently in the progenitors of the secretory microvillar cells and Bowman's glands in the OE, expression being abolished by 2 months of age (PubMed:27910949). Also expressed at the canalicular stage, at 15.5 days post coitum (dpc), in the large excretory duct of the developing salivary glands (PubMed:18572159). By the terminal bud stage, just prior to birth, at 17.5 dpc, expressed in a small number of cells in ductal structures of all three major salivary glands (PubMed:18572159). At three weeks of age, expressed in duct cells in the submandibular, sublingual and parotid glands (PubMed:18572159).|||Following injury of the olfactory epithelium (OE) in 3-4 week olds, up-regulated in the multipotent horizontal basal cells (HBCs) at between 1 and 28 days later.|||Nucleus|||Transcriptional repressor (PubMed:11784080). Inhibits myogenesis (PubMed:11784080). Plays a role in progenitor cells which differentiate into ductal and acinar, but not myoepithelial, cell lineages in the salivary glands (PubMed:18572159, PubMed:21377457). Involved in the functions of the microvillar cells and Bowman's glands and probably, in a non-cell-autonomous manner, in the development or regeneration of a complete olfactory epithelium (OE) (PubMed:27910949).|||Viable and fertile (PubMed:21377457, PubMed:27910949). Salivary glands develop, but the submandibular glands are consistently smaller and overall levels of cell proliferation lower (PubMed:21377457). Expression of cation-chloride cotransporter Nkcc1 is dramatically reduced in salivary ducts (PubMed:21377457). No obvious morphological changes in the olfactory epithelium (OE) (PubMed:27910949). http://togogenome.org/gene/10090:1810055G02Rik ^@ http://purl.uniprot.org/uniprot/Q9D8N1 ^@ Subcellular Location Annotation ^@ Cell membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Pigq ^@ http://purl.uniprot.org/uniprot/Q9QYT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGQ family.|||Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts with PIGA, PIGH and PIGC.|||Membrane|||Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. http://togogenome.org/gene/10090:Xpo6 ^@ http://purl.uniprot.org/uniprot/Q924Z6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the exportin family.|||Cytoplasm|||Found in a complex with XPO6, Ran, ACTB and PFN1. Interacts with ACTB. Interacts with ACTB in a RanGTP-dependent manner.|||Mediates the nuclear export of actin and profilin-actin complexes in somatic cells.|||Nucleus http://togogenome.org/gene/10090:Akap8 ^@ http://purl.uniprot.org/uniprot/Q059U9|||http://purl.uniprot.org/uniprot/Q9DBR0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AKAP8 and FIGN double mutant mice die soon after birth due to cleft palate.|||Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (By similarity). Specifically involved in recruitment of CAPD2 to, and condensation of maternal but not paternal chromosomes (PubMed:12082153). May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L. Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation. May be involved in regulation of DNA replication by acting as scaffold for MCM2. Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation. May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells. May act as a carrier protein of GJA1 for its transport to the nucleus. May play a repressive role in the regulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and transcribed regions (By similarity). Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (PubMed:19531803).|||Belongs to the AKAP95 family.|||Binds to the PKA RII-alpha regulatory subunit PRKAR2A (By similarity). Interacts (via C-terminus) with FIGN (PubMed:16751186). Interacts with NCAPD2, CCND3, CCNE1, MCM2, RPS6KA1, DDX5, PDE4A (By similarity). Interacts with MYCBP; MYCBP is translocated to the nucleus and the interaction prevents the association of the PKA catalytic subunit leading to suppression of PKA activity (PubMed:12414807). Interacts with CCND1, CASP3 (PubMed:14641107, PubMed:16227597). Interacts with NFKB1; detetcted in the cytoplasm (PubMed:19531803). Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex. Interacts with HDAC3; increased during mitosis. Interacts with GJA1; in the nucleus and in the nuclear membrane; the nuclear association increases with progress of cell cycle G1, S and G2 phase and decreases in M phase (By similarity).|||Cytoplasm|||Nucleus matrix|||Phosphorylated on tyrosine residues probably by SRC subfamily protein kinases; multiple phosphorylation is leading to dissociation from nuclear structures implicated in chromatin structural changes.|||Weakly expressed in metaphase II oocytes. Strongly up-regulated after fertilization at the pronuclear stage and restricted to the female pronucleus. Subsequently localized to the nucleus of each blastomere and on condensed chromosomes in mitotic cells.|||nucleolus http://togogenome.org/gene/10090:Imp3 ^@ http://purl.uniprot.org/uniprot/Q921Y2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS4 family.|||Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Component of a heterotrimeric complex containing IMP3, IMP4 and MPHOSPH10. Interacts with MPHOSPH10.|||nucleolus http://togogenome.org/gene/10090:Slc39a7 ^@ http://purl.uniprot.org/uniprot/A0A068BIT0|||http://purl.uniprot.org/uniprot/Q31125 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ZIP transporter (TC 2.A.5) family. KE4/Catsup subfamily.|||Down-regulated in an insulin-resistant, and high-fat diet state.|||Endoplasmic reticulum membrane|||Homodimer.|||Membrane|||Methylation at some His residue by METTL9 leads to reduced zinc-binding.|||Rapidly phosphorylated by CK2 following Zn(2+) treatment. This phosphorylation is required for efficient cytosolic Zn(2+) release.|||Transports Zn(2+) from the endoplasmic reticulum (ER)/Golgi apparatus to the cytosol, playing an essential role in the regulation of cytosolic zinc levels (PubMed:15705588). Acts as gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation, resulting in activation of multiple downstream pathways leading to cell growth and proliferation (By similarity). Has an essential role in B cell development and is required for proper B cell receptor signaling (PubMed:30718914). Plays an important role in maintaining intestinal epithelial homeostasis and skin dermis development by regulating ER function (PubMed:28545780, PubMed:27736879). Controls cell signaling pathways involved in glucose metabolism in skeletal muscle (PubMed:31266232). Has a protective role against ER stress in different biological contexts (PubMed:31266232). Mediates Zn(2+)-induced ferroptosis (By similarity).|||Widely expressed (PubMed:15705588, PubMed:2294398). Highly expressed in the intestinal crypts (PubMed:27736879).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Mapk4 ^@ http://purl.uniprot.org/uniprot/Q6P5G0 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation at Ser-186.|||Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Cytoplasm|||Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5.|||In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.|||Nucleus|||Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.|||The FRIEDE motif is required for docking MAPKAPK5. http://togogenome.org/gene/10090:Pcdhgc3 ^@ http://purl.uniprot.org/uniprot/Q91XX1 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Mpnd ^@ http://purl.uniprot.org/uniprot/Q3TV65 ^@ Domain|||Function|||PTM|||Similarity ^@ Belongs to the peptidase M67 family.|||Degraded following binding to N(6)-methyladenosine methylated DNA (m6A).|||Probable protease (By similarity). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its degradation (By similarity).|||The RAMA domain recognizes and binds N(6)-methyladenosine methylation on DNA (m6A). http://togogenome.org/gene/10090:Nfkb2 ^@ http://purl.uniprot.org/uniprot/Q3UG25|||http://purl.uniprot.org/uniprot/Q3UV15|||http://purl.uniprot.org/uniprot/Q9WTK5 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the NF-kappa-B RelB-p52 complex. Homodimer; component of the NF-kappa-B p52-p52 complex. Component of the NF-kappa-B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex. NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 (By similarity). Directly interacts with MEN1 (By similarity).|||Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.|||Cytoplasm|||Highly expressed in lymph nodes and thymus.|||NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65 (By similarity). In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer.|||Nucleus|||Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.|||The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation.|||The glycine-rich region (GRR) appears to be a critical element in the generation of p52.|||While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p52 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing (By similarity). http://togogenome.org/gene/10090:Midn ^@ http://purl.uniprot.org/uniprot/Q3TPJ7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed at high levels in brain and liver with significantly lower levels in muscle.|||Facilitates ubiquitin-independent proteasomal degradation of polycomb protein CBX4 (PubMed:27326929). Plays a role in inhibiting the activity of glucokinase GCK and both glucose-induced and basal insulin secretion (By similarity).|||Interacts with GCK; the interaction occurs preferentially at low glucose levels.|||Nucleus|||Strongly expressed at the mesencephalon (midbrain) of 12.5 dpc embryos.|||cytosol|||nucleolus http://togogenome.org/gene/10090:Gldn ^@ http://purl.uniprot.org/uniprot/Q8BMF8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in sciatic nerve (at protein level) (PubMed:17293346, PubMed:20188654, PubMed:24719088). Widely expressed with higher expression in testis and skeletal muscle (PubMed:12642876).|||Homotrimer (via collagen-like domains) (PubMed:17293346). Interacts with NRCAM and NFASC/neurofascin (PubMed:16039564, PubMed:20188654). Interaction with glial NRCAM enhances interaction with axonal NFASC (PubMed:20188654). Interacts with MYOC (PubMed:23897819).|||Ligand for NRCAM and NFASC/neurofascin that plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Mediates interaction between Schwann cell microvilli and axons via its interactions with NRCAM and NFASC (PubMed:20188654). Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters (PubMed:20188654). Required, together with NRCAM, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier (PubMed:24719088).|||Mutant mice present no obvious neurological phenotype and have normal nerve conduction. Nerves from their peripheral nervous system have myelin sheets that are indistinguishable from wild-type. In contrast, they present impaired and disorganized attachment of Schwann cell microvilli to the axolemma at nodes of Ranvier. Mature nodes are formed by the fusion of two heminodes. During development, mutant mice present defective clustering of sodium channels at heminodes, but display normal sodium channel clustering at mature nodes (PubMed:20188654). Mice lacking both Gldn and Nrcam are born at the expected Mendelian rate, but are smaller than control littermates and display important neurological impairments, in spite of seemingly normal nerve myelination. Motor abnormalities vary between individuals, ranging from ataxia, uncoordinated movements and premature death to weakness of the hind limbs, hypomotility, strongly impaired ability to hang from a horizontal bar with their forelimbs and a tendency to stumble. The motor defects correlate with decreased velocity of nerve conduction and slower propagation of action potentials. Most mice die within 60 days after birth, and none are fertile. Mutant mice display delayed formation of mature nodes of Ranvier; 15 days after birth about 20% of the nodes lack detectable sodium channel clusters. Sodium channel clustering and nerve conduction appear normal 60 and 75 days after birth, but subsequently a gradual disintegration of the nodal protein complexes is seen. About 70% of the mutant nodes present high-density sodium channel clustering at 120 days after birth, as opposed to nearly 100% for wild-type. Contrary to wild-type, in adult nodes of Ranvier the sodium channels are often clustered near the paranode border with an empty gap in the middle. At nodes of Ranvier, Schwann cell microvilli are sparse or absent and show defects in their orientation, resulting in various structural abnormalities at the node and the paranode border (PubMed:24719088).|||N-glycosylated.|||Proteolytic proccessing by a furin-like protease causes shedding of the ectodomain. Further cleavage by BMP1 releases the olfactomedin-like domain.|||Secreted|||The olfactomedin-like domain mediates NFASC/neurofascin and NRCAM binding.|||axon|||extracellular matrix http://togogenome.org/gene/10090:Aoc1l1 ^@ http://purl.uniprot.org/uniprot/Q6IMK7 ^@ Cofactor|||PTM|||Similarity ^@ Belongs to the copper/topaquinone oxidase family.|||Contains 1 topaquinone per subunit.|||Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. http://togogenome.org/gene/10090:Slc35a3 ^@ http://purl.uniprot.org/uniprot/Q8R1T4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.|||Golgi apparatus membrane|||Interacts with SLC35A2; the interaction is reduced in the presence of SLC35A4. Found in a complex with SLC35A2 and SLC35A4. Interacts with MGAT4B.|||O-Glcnacylation regulates the stability of SLC35A3 and the specific complex formation with MGAT4B.|||Transports diphosphate-N-acetylglucosamine (UDP-GlcNAc) from the cytosol into the lumen of the Golgi apparatus, functioning as an antiporter that exchanges UDP-N-acetyl-alpha-D-glucosamine for UMP (PubMed:31118275). May supply UDP-GlcNAc as substrate for Golgi-resident glycosyltransferases that generate highly branched, multiantennary complex N-glycans and keratan sulfate (By similarity). However, the exact role of SLC35A3 still needs to be elucidated, it could be a member of a catalytically more efficient multiprotein complex rather than function independently as a single transporter (By similarity). http://togogenome.org/gene/10090:Ccl21d ^@ http://purl.uniprot.org/uniprot/P86792|||http://purl.uniprot.org/uniprot/P86793 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Binds to CCR7 and to CXCR3. Interacts with PDPN; relocalizes PDPN to the basolateral membrane.|||Expressed strongly in lung, spleen, thymus, peripheral and mesentric lymph nodes. Also expressed in the testis, kidney, liver, and heart.|||Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Potent mesangial cell chemoattractant. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs.|||Secreted|||Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c produce identical proteins while the protein produced by Ccl21a differs at only one position. Ccl21b and Ccl21c have Leu-65 (6Ckine-Leu) while Ccl21a has 'Ser-65' (6Ckine-Ser). http://togogenome.org/gene/10090:Il21 ^@ http://purl.uniprot.org/uniprot/E9PX58|||http://purl.uniprot.org/uniprot/Q5SUE2|||http://purl.uniprot.org/uniprot/Q9ES17 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the IL-15/IL-21 family.|||Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (PubMed:15100251). Implicated in the generation and maintenance of T follicular helper (Tfh) cells and the formation of germinal-centers. Together with IL6, control the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection (PubMed:23045607). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15 (PubMed:11970879). May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells (By similarity). During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation (PubMed:12893770).|||Expressed in CD4(+) T cells.|||In CD4(+) T cells, expression is induced upon influenza virus infection by IL6.|||Mutants infected with influenza virus do not show a significant difference on germinal center B cells compared to wild-types (PubMed:23045607). Double knockouts for IL21 and IL6 infected with influenza virus show a significant reduction in germinal centers in both the draining lymphatic nodes and the spleens compared to wild-types. Animals show a significant reduction in virus-specific IgM and IgG (PubMed:23045607).|||Secreted http://togogenome.org/gene/10090:Adcy4 ^@ http://purl.uniprot.org/uniprot/Q91WF3 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by forskolin. Insensitive to calcium/calmodulin. Stimulated by GNAS and by the G-protein beta and gamma subunit complex.|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).|||Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.|||Cell membrane|||Cytoplasm|||The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules. http://togogenome.org/gene/10090:Aqp5 ^@ http://purl.uniprot.org/uniprot/Q9WTY4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).|||Belongs to the MIP/aquaporin (TC 1.A.8) family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Detected at the luminal membrane of secretory epithelial cells in hindpaw sweat glands (PubMed:12042359, PubMed:23473857). Detected in acinar cells in salivary glands, in duct cells in lacrimal glands and in lung (at protein level) (PubMed:10337625, PubMed:10400615, PubMed:10619865, PubMed:16571723, PubMed:18027168). Detected in lung, parotid, submandibular, sublingual, and lacrimal gland tissues (PubMed:10337625).|||Forms a water-specific channel (By similarity). Plays an important role in fluid secretion in salivary glands (PubMed:10400615, PubMed:16571723, PubMed:18027168). Required for TRPV4 activation by hypotonicity. Together with TRPV4, controls regulatory volume decrease in salivary epithelial cells (PubMed:16571723). Seems to play a redundant role in water transport in the eye, lung and in sweat glands (PubMed:10619865, PubMed:12042359, PubMed:18027168).|||Homotetramer (By similarity). Interacts with TRPV4; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (PubMed:16571723).|||Homozygous mice are born at less than the expected Mendelian rate, indicative of embryonic lethality (PubMed:10400615, PubMed:10619865). After weaning, mice display decreased pilocarbine-induced saliva secretion, and their saliva displays increased osmolality and viscosity (PubMed:10400615, PubMed:18027168). Mice display reduced Ca2+ entry and loss of regulatory volume decrease in response to hypotonicity in acinar cells. HTS-stimulated Ca2+ entry is significantly decreased in submandibular gland acini and almost completely abolished in parotid acini (PubMed:16571723). Lung airspace-capillary osmotic water permeability is strongly decreased. In contrast, there is no change in alveolar fluid clearance (PubMed:10619865). Paws of mutant mice display normal sweat secretion (PubMed:12042359). Tear secretion is not changed in mutant mice (PubMed:18027168). http://togogenome.org/gene/10090:Dynll1 ^@ http://purl.uniprot.org/uniprot/P63168 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures (By similarity).|||Belongs to the dynein light chain family.|||Binds and inhibits the catalytic activity of neuronal nitric oxide synthase/NOS1.|||Homodimer. Monomer; the monomeric form is incapable of binding to target proteins. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with TXNDC17. Interacts with WWC1 and ESR1. The interaction with WWC1 is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin. Interacts with BCL2; the interaction is greatly enhanced in the nucleus and in mitochondria upon induction of apoptosis. Interacts with PAK1; the interaction requires dimeric DYNLL1. Interacts with MYZAP. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with ATMIN; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. Interacts with NEK9 (not phosphorylated at 'Ser-944') (By similarity). Interacts with BCL2L11 (PubMed:21478148). Interacts with BICD2 (PubMed:22956769). Interacts with BCAS1 (By similarity). Interacts with Bassoon/BSN (By similarity). Interacts with HDAC6 (By similarity). Interacts with TPPP (By similarity). Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton (By similarity). Interacts with FAM83D/CHICA (via C-terminus) (By similarity). Interacts with HMMR, SPAG5/Astrin and KNSTRN/Kinastrin (By similarity). Interacts with TLK2 (By similarity). Interacts with NOS1 (By similarity).|||Mitochondrion|||Nucleus|||Phosphorylation at Ser-88 appears to control the dimer-monomer transition.|||Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.|||Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity (By similarity).|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Egr2 ^@ http://purl.uniprot.org/uniprot/P08152|||http://purl.uniprot.org/uniprot/Q3U207 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-247. May be deacetylated by HDAC6, HDAC10 or SIRT1.|||Activated during G0/G1 transition in cultured cells.|||Before 8 dpc, expressed in the future rhombomere r3 at 0-3 somites, followed by expression in rhombomere r5 in 4-7 somites at 8 dpc, and maintained until 12 somites (PubMed:8093858). Expressed in migrating neural crest cells from r5/r6 (PubMed:8093858). Expressed in boundary cap cells that surround nerve exit points from the central nervous system at 10.5 dpc (PubMed:7935840, PubMed:8093858). Up to 14.5 dpc, expressed in motor and sensory roots of cranial and spinal nerves (PubMed:7935840). After 15.5 dpc, expressed in the entire peripheral nervous system (PubMed:7935840). Expressed in the embryonic nervous system (PubMed:17938205). Expressed in myelinating Schwann cells 2 weeks after birth (PubMed:7935840).|||Belongs to the EGR C2H2-type zinc-finger protein family.|||E3 SUMO-protein ligase helping SUMO1 conjugation to its coregulators NAB1 and NAB2, whose sumoylation down-regulates EGR2 transcriptional activity.|||Expressed mainly in the thymus.|||Failure to promote expression of the Hoxb3 reporter in rhombomere r5 in the hindbrain (PubMed:11823429). Changed morphology of the sciatic nerves, with a higher density of Schwann cells, and a reduction in major components of compacted myelin, including lipidic components, as well as myelin proteins Mpz and Mbp (PubMed:7935840). Schwann cells in the sciatic nerves exhibit increased expression of Scip, reduced expression of Mpz, elevated mitotic activity and increased apoptosis at postnatal day P12 (PubMed:10068633). Total absence of myelin along the axons of sciatic nerves at postnatal day P15 (PubMed:7935840). Does not seem to affect the myelination in the central nervous system (PubMed:7935840). Signs of atrophy in the jaw openener anterior digastric (AD) and mylohoid (MY) muscles at 15 dpc with smaller diameter fibers, fibers with triangular shape, increased amount of connective tissue surrounding the fibers, suggesting a lack of neural innervation (PubMed:11509834). Reduced volume of the delineated trigeminal motor nucleus and restructuring of the brainstem at 15 dpc (PubMed:11509834). Reduced volume in both AD and MY musculature and reduced milk indigestion after birth (PubMed:11509834).|||Interacts with HCFC1 (By similarity). Interacts with WWP2 (PubMed:19651900). Interacts with UBC9 (By similarity). Interacts with CITED1 (PubMed:17938205). Interacts (via phosphorylated form) with SFN (PubMed:17938205).|||Nucleus|||Sequence-specific DNA-binding transcription factor (PubMed:1969796, PubMed:1674431, PubMed:11823429, PubMed:31852952). Plays a role in hindbrain segmentation by regulating the expression of a subset of homeobox containing genes and in Schwann cell myelination by regulating the expression of genes involved in the formation and maintenance of myelin (PubMed:1969796, PubMed:1674431, PubMed:11823429, PubMed:31852952, PubMed:8093858). Binds to two EGR2-consensus sites EGR2A (5'-CTGTAGGAG-3') and EGR2B (5'-ATGTAGGTG-3') in the HOXB3 enhancer and promotes HOXB3 transcriptional activation (PubMed:11823429). Binds to specific DNA sites located in the promoter region of HOXA4, HOXB2 and ERBB2 (PubMed:1969796, PubMed:8093858, PubMed:17938205). Regulates hindbrain segmentation by controlling the expression of Hox genes, such as HOXA4, HOXB3 and HOXB2, and thereby specifying odd and even rhombomeres (PubMed:11823429, PubMed:1674431). Promotes the expression of HOXB3 in the rhombomere r5 and of HOXB3 in r3 and r5 in the hindbrain (PubMed:11823429, PubMed:8093858). Regulates myelination in the peripheral nervous system after birth, possibly by regulating the expression of myelin proteins, such as MPZ, and by promoting the differentiation of Schwann cells (PubMed:7935840, PubMed:10068633). Involved in the development of the jaw openener musculature, probably by playing a role in its innervation through trigeminal motor neurons (PubMed:11509834). May play a role in adipogenesis, possibly by regulating the expression of CEBPB (PubMed:16054051).|||Ubiquitinated by WWP2 leading to proteasomal degradation. http://togogenome.org/gene/10090:Vmn1r3 ^@ http://purl.uniprot.org/uniprot/A2AMT7 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Dnah1 ^@ http://purl.uniprot.org/uniprot/E9Q8T7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynein heavy chain family.|||Consists of at least two heavy chains and a number of intermediate and light chains.|||Force generating protein of cilia required for sperm flagellum motility (PubMed:11371505). Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP (By similarity). Required in spermatozoa for the formation of the inner dynein arms and biogenesis of the axoneme (By similarity).|||Mice are viable and show no malformations; however, homozygous males are infertile, due to inability of spermatozoa to move from the uterus into the oviduct. Spermatozoa show decreased motility. In addition, tracheal beating frequency is reduced.|||cilium axoneme|||flagellum http://togogenome.org/gene/10090:Slx1b ^@ http://purl.uniprot.org/uniprot/Q8BX32 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLX1 family.|||Catalytic subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products.|||Expressed in testis, colon, bone marrow, brain, thymus and to a lesser extent in heart, kidney, skeletal muscle and spleen.|||Forms a heterodimer with SLX4.|||Nucleus http://togogenome.org/gene/10090:Dusp1 ^@ http://purl.uniprot.org/uniprot/P28563|||http://purl.uniprot.org/uniprot/Q3U8K3 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle.|||Expression in lung increases after birth.|||Nucleus|||Phosphorylation at Ser-359 and Ser-364 by MAPK1/ERK2 and MAPK3/ERK1 reduces its rate of degradation.|||Up-regulated by growth factors and mitogens. http://togogenome.org/gene/10090:Ackr4 ^@ http://purl.uniprot.org/uniprot/B2RU75|||http://purl.uniprot.org/uniprot/Q924I3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus and inhibits spontaneous autoimmunity.|||Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.|||Cell membrane|||Early endosome|||Expressed in lung, heart, spleen, skeletal muscle, testis, astrocytes and microglia. Expressed by cortical thymic epithelial cells.|||Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2 (By similarity).|||Membrane|||Mice have a larger thymus with relatively fewer cortical thymic epithelial cells and this is associated with severe reductions in cortical CCL25 distribution and accumulation of DN2 thymocyte precursor cells in the medulla. The downstream effects materialize in reduced proportions of DN3 cells and significantly reduced numbers of cortical DN3 cells. Aberrant thymocyte development culminates in increased prevalence of spontaneous autoimmune-like disease, characterized by lymphocytic infiltration of peripheral organs.|||Recycling endosome|||The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated. http://togogenome.org/gene/10090:Cwf19l1 ^@ http://purl.uniprot.org/uniprot/Q8CI33 ^@ Sequence Caution|||Similarity ^@ Belongs to the CWF19 family.|||Contaminating sequence. Potential poly-A sequence. http://togogenome.org/gene/10090:Or10g3b ^@ http://purl.uniprot.org/uniprot/L7N457 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or13c7 ^@ http://purl.uniprot.org/uniprot/Q9QZ22 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tuba4a ^@ http://purl.uniprot.org/uniprot/P68368 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.|||Although this tubulin does not encode a C-terminal tyrosine, a C-terminal tyrosine can be added post-translationally by the tubulin tyrosine ligase (TTL). It can then undergo a detyrosination cycle by the tubulin tyrosine carboxypeptidase (KIAA0895L/MATCAP).|||Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with CFAP157 (PubMed:27965440).|||Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREC motif may be critical for tubulin autoregulation.|||This tubulin does not have a C-terminal tyrosine.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Cdsn ^@ http://purl.uniprot.org/uniprot/Q7TPC1 ^@ Function|||Subcellular Location Annotation ^@ Important for the epidermal barrier integrity.|||Secreted http://togogenome.org/gene/10090:Eef1d ^@ http://purl.uniprot.org/uniprot/A0A0R4J1E2|||http://purl.uniprot.org/uniprot/A0A0R4J1L2|||http://purl.uniprot.org/uniprot/P57776|||http://purl.uniprot.org/uniprot/Q80T06|||http://purl.uniprot.org/uniprot/Q91VK2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EF-1-beta/EF-1-delta family.|||EF-1 is composed of 4 subunits: alpha, beta, delta isoform 1, and gamma. Isoform 3 interacts with HSF1 and NFE2L2.|||EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.|||Nucleus|||Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE). http://togogenome.org/gene/10090:Plxnb3 ^@ http://purl.uniprot.org/uniprot/Q9QY40 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Binds MET and MST1R. Interacts with RIT2/RIN. May form homodimers (via Sema domain) (By similarity). Interacts (via cytoplasmic domain) with FSCN1, ARHGDIA and RAC1.|||Cell membrane|||Expressed in brain (at protein level). In cerebellum, strongest expression detected in Purkinje and granular cells. Detected at very low levels in several fetal tissues, including dorsal root ganglia (DRG), heart, lung, optic bulb, brain and liver.|||In brain, detected first perinatally, with expression reaching maximal levels at postnatal day 9 (P9). In the developing nervous system, barely detectable until birth, and postnatally expressed in white matter tracks including the corpus callosum, external capsule, fimbria hippocampi and corticospinal tracts. In spinal cord, not detected until birth, and postnatally expressed in spinal white matter. In cerebellum, expressed only in cerebellar white matter cells, with expression detected first shortly after birth in the cerebellar peduncle and increasing progressively in the white matter tracts of the cerebellar lobes until P10.|||Mutant mice are viable and fertile and display no obvious morphological abnormalities in the brain or spinal cord.|||Receptor for SEMA5A that plays a role in axon guidance, invasive growth and cell migration. Stimulates neurite outgrowth and mediates Ca(2+)/Mg(2+)-dependent cell aggregation. In glioma cells, SEMA5A stimulation of PLXNB3 results in the disassembly of F-actin stress fibers, disruption of focal adhesions and cellular collapse as well as inhibition of cell migration and invasion through ARHGDIA-mediated inactivation of RAC1 (By similarity). Seem to be non-essential for normal development and function of the central nervous system. http://togogenome.org/gene/10090:Tle5 ^@ http://purl.uniprot.org/uniprot/B7ZNK7|||http://purl.uniprot.org/uniprot/P63002|||http://purl.uniprot.org/uniprot/Q3TYD9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat Groucho/TLE family.|||Expressed in the developing eye and forebrain of embryos.|||Homooligomer and heterooligomer with other family members. Binds TCF7 and the NF-kappa-B subunit RELA. Interacts with PHF12 (By similarity). Interacts (via Q domain) with SIX3. Interacts with SIX6.|||Lacks the C-terminal WD repeats.|||Nucleus|||Transcriptional corepressor. Acts as dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development.|||Ubiquitinated by XIAP/BIRC4.|||Ubiquitously expressed in developing embryos by midgestation, a wide expression is conserved in adult. In mouse, abundantly expressed in muscle, heart and brain. http://togogenome.org/gene/10090:Rasef ^@ http://purl.uniprot.org/uniprot/Q5RI75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Binds predominantly GDP, and also GTP (By similarity). Acts as a dynein adapter protein that activates dynein-mediated transport and dynein-dynactin motility on microtubules (By similarity).|||Homodimer (By similarity). Interacts with the dynein-dynactin complex (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Prss39 ^@ http://purl.uniprot.org/uniprot/O70169 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Expressed in testis. More specifically, abundantly expressed in the haploid round spermatid.|||In contrast to other members of the family, lacks the conserved Asp at position 158, which is replaced by an Asn residue, suggesting it is inactive.|||May play an important role in the sperm/egg interaction; released during the acrosome reaction.|||Secreted|||There appears to be no human ortholog of this protein.|||acrosome http://togogenome.org/gene/10090:Zdhhc18 ^@ http://purl.uniprot.org/uniprot/Q5Y5T2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.|||Golgi apparatus membrane|||Mice were born at the expected Mendelian ratio, develop normally and are fertile (PubMed:35438208). Mice display increased resistance to infection by DNA viruses due to increased activation of the cGAS-STING pathway (PubMed:35438208).|||Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates, such as CGAS, HRAS and LCK (PubMed:15603741, PubMed:35438208). Palmitoylates HRAS and LCK (PubMed:15603741). Acts as a negative regulator of the cGAS-STING pathway be mediating palmitoylation and inactivation of CGAS (PubMed:35438208). May also have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and therefore regulate G protein-coupled receptor signaling (By similarity).|||The DHHC domain is required for palmitoyltransferase activity.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Hmcn1 ^@ http://purl.uniprot.org/uniprot/D3YXG0 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell junction|||Cleavage furrow|||Cytoplasm|||Expression increases with age from 3 weeks to 15-20 weeks (at protein level).|||Has been shown in one study to play a role in cleavage furrow maturation during cytokinesis (PubMed:21215633). However, other studies have shown no role in this process (PubMed:32035013, PubMed:34504132).|||In the kidney, expressed in the glomerulus (at protein level) (PubMed:29488390, PubMed:32035013). Expressed in whisker and hair follicles, eye, tongue, and splenic and lymph node conduits (at protein level) (PubMed:32035013). In the embryo, localizes to the cleavage furrow at the two-cell stage (at protein level) (PubMed:34504132). In neonatal skin, expressed throughout the dermis (at protein level) (PubMed:34504132). In adult skin, strongly concentrated at the dermal side of the basement membrane but not detectable in the deeper dermis (PubMed:34504132). Shows tendon-specific localization at the myotendinous junction and is also detected in the perichondrium (at protein level) (PubMed:34504132). Expressed by chondrocytes residing in articular cartilage and the femoral growth plate of 52 week old mice (at protein level) (PubMed:34504132). Expressed in vascular endothelial cells in coronary arteries and sparsely in endocardial endothelium (at protein level) (PubMed:24951538). Expressed in skin, tongue, lung and eye (PubMed:17015624). At 14.5 dpc, expressed in the vibrissae, dermis, forelimb, kidney, intestine, lung and iliac cartilage where expression is found mainly in mesenchymal cells (PubMed:34504132).|||Induced by high glucose and transforming growth factor beta (at protein level) (PubMed:29488390). Following wounding, up-regulated in the dermis adjacent to the epidermal tongues of closing wounds (at protein level) (PubMed:34504132). Up-regulated following myocardial infarction.|||Involved in transforming growth factor beta-mediated rearrangement of the podocyte cytoskeleton which includes reduction of F-actin fibers and broadening, flattening and elongation of podocytes (By similarity). Plays a role in basement membrane organization (PubMed:34504132). May promote cleavage furrow maturation during cytokinesis in preimplantation embryos (PubMed:21215633). May play a role in the architecture of adhesive and flexible epithelial cell junctions (PubMed:17015624). May play a role during myocardial remodeling by imparting an effect on cardiac fibroblast migration (PubMed:24951538).|||Mutants are viable and fertile with no gross phenotypes (PubMed:32035013, PubMed:34504132). Ultrastructural basement membrane alterations are observed at dermal-epidermal and myotendinous junctions (PubMed:34504132). However, another study showed that embryos arrest between the one- and four-cell stages with cleavage furrows that form but fail to ingress and often retract prior to completion, resulting in multinucleate cells (PubMed:21215633). Double knockout of Hmcn1 and Hmcn2 results in no overt phenotypes with mice being viable and fertile (PubMed:32035013).|||basement membrane http://togogenome.org/gene/10090:Aadac ^@ http://purl.uniprot.org/uniprot/Q99PG0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 'GDXG' lipolytic enzyme family.|||Displays cellular triglyceride lipase activity in liver, increases the levels of intracellular fatty acids derived from the hydrolysis of newly formed triglyceride stores and plays a role in very low-density lipoprotein assembly (By similarity). Displays serine esterase activity in liver. Deacetylates a variety of arylacetamide substrates, including xenobiotic compounds and procarcinogens, converting them to the primary arylamide compounds and increasing their toxicity.|||Endoplasmic reticulum membrane|||Highest levels in liver with lower levels in jejunum and kidney.|||Microsome membrane|||N-glycosylated. http://togogenome.org/gene/10090:Cavin2 ^@ http://purl.uniprot.org/uniprot/Q63918 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAVIN family.|||Binds phosphatidylserine (PS) in a calcium-independent manner. PS-binding is inhibited by phosphotidic acid and phosphatidylinositol. Does not bind phosphatidylcholine (By similarity).|||Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4 (PubMed:19546242). Binds to PRKCA in the presence of phosphatidylserine. Interacts with CAVIN4; this augments the transactivation of NPPA by CAVIN4 (By similarity). Interacts with CAVIN1 (PubMed:25588833, PubMed:19546242). Interacts with CAV3 (By similarity).|||Expression gradually increases during embryonic stages and reaches a maximum in neonates.|||Heart, adipose tissue, lung and endothelial cells (at protein level). Highly expressed in kidney and expressed at lower levels in liver, spleen, thymus, stomach, intestine and uterus.|||Mice show loss of endothelial caveolae in lung and adipose tissue but no effect on the abundance of endothelial caveolae in the heart.|||Plays an important role in caveolar biogenesis and morphology. Regulates caveolae morphology by inducing membrane curvature within caveolae (By similarity). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in the lung and fat endothelia but not in the heart endothelia. Negatively regulates the size or stability of CAVIN complexes in the lung endothelial cells (PubMed:23652019). May play a role in targeting PRKCA to caveolae (By similarity).|||The N-terminus is blocked.|||The leucine-zipper domain is essential for its localization in the caveolae.|||Up-regulated in response to cardiac hypertrophy and in serum-starved but not in density-dependent growth-arrested NIH3T3 cells. Down-regulated within 6 hours after the addition of serum or epidermal growth factor to serum-starved cells.|||caveola|||cytosol http://togogenome.org/gene/10090:Paip2 ^@ http://purl.uniprot.org/uniprot/Q9D6V8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a repressor in the regulation of translation initiation of poly(A)-containing mRNAs. Its inhibitory activity on translation is mediated via its action on PABPC1. Displaces the interaction of PABPC1 with poly(A) RNA and competes with PAIP1 for binding to PABPC1. Its association with PABPC1 results in disruption of the cytoplasmic poly(A) RNP structure organization (By similarity).|||Belongs to the PAIP2 family.|||Cytoplasm|||Expressed at high levels in testis with expression also detected in heart, brain, lung, liver, kidney, pancreas and small intestine (at protein level).|||Interacts with the second and third RRM domains and C-terminus regions of PABPC1 in a 2:1 stoichiometry.|||Only the PABPC1-interacting motif-1 (PAM1) interferes with the binding of PABPC1 to poly(A) RNA and translation initiation.|||Ubiquitinated, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Grhl2 ^@ http://purl.uniprot.org/uniprot/Q8K5C0|||http://purl.uniprot.org/uniprot/Q9DCN4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 14.5 dpc expressed in lung, esophagus, skin and kidney. At 9.5 dpc expressed in foregut and surface ectoderm but not in the neural tube. At 9.5 dpc and 15.5 dpc, detected in the lung epithelium and in branchiolar and alveolar epithelial cells at 18.5 dpc and adult. Expressed in otocyst at 11.5 dpc, prominent in epithelial derivatives of the otic placode in the vestibule and cochlear duct at 18.5 dpc. At postnatal day 5, epithelial cells of the cochlear duct, which surround the endolymph-containing scala media, continued to express low levels, while little or no expression was seen in the mesenchyme-derived cells lining the scala tympani and scala vestibuli. Detected in cholangiocytes in postnatal day 1 and postnatal day 8 livers.|||Belongs to the grh/CP2 family. Grainyhead subfamily.|||GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxal lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.|||Homodimer, also forms heterodimers with GRHL1 or GRHL3.|||Membrane|||Mutant embryos show an epithelial and anterior and posterior neural tube defects leading to death at around 11.5 dpc (PubMed:20654612, PubMed:20978075). They exhibit a fully penetrant split-face malformation, associated with cranioschisis. Closure of the remainder of the neural tube ocrurred normally with the exception of the posterior neuropore. The dorso-lateral hinge points fail to form and closure do not proceed beyond this point (PubMed:20654612).|||Nucleus|||Transcription factor playing an important role in primary neurulation and in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (PubMed:22696678). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (PubMed:20654612). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (PubMed:22696678). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia (PubMed:20978075). Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events such as eyelid fusion and epidermal wound repair (PubMed:21081122). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (PubMed:22955271). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity. In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (By similarity). http://togogenome.org/gene/10090:Eeig2 ^@ http://purl.uniprot.org/uniprot/E9Q4R1|||http://purl.uniprot.org/uniprot/Q8BQS4 ^@ Similarity|||Tissue Specificity ^@ Belongs to the EEIG family.|||Expressed in bone marrow-derived macrophages. http://togogenome.org/gene/10090:Cdc42bpb ^@ http://purl.uniprot.org/uniprot/Q7TT50 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.|||Cell junction|||Cell membrane|||Cytoplasm|||Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42. Interacts with TJP1; this interaction requires the presence of catalytically active CDC42. Forms a tripartite complex with MYO18A and LURAP1 with the latter acting as an adapter connecting CDC42BPB and MYO18A. LURAP1 binding results in activation of CDC42BPB by abolition of its negative autoregulation. Interacts with STRIP1, STRN3 and SIKE1 (By similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with LURAP1 (By similarity). Interacts (via AGC-kinase C-terminal domain) with FAM89B/LRAP25 (via LRR repeat)(PubMed:25107909). Forms a tripartite complex with FAM89B/LRAP25 and LIMK1 (PubMed:25107909).|||Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation. Inhibited by chelerythrine chloride (By similarity).|||Proteolytically cleaved by caspases upon apoptosis induction.|||Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2. In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration. Phosphorylates PPP1R12A (By similarity). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (PubMed:25107909).|||lamellipodium http://togogenome.org/gene/10090:Nipsnap2 ^@ http://purl.uniprot.org/uniprot/Q7TMG8 ^@ Similarity ^@ Belongs to the NipSnap family. http://togogenome.org/gene/10090:Pdzd8 ^@ http://purl.uniprot.org/uniprot/B9EJ80 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with MSN.|||Molecular tethering protein that connects endoplasmic reticulum and mitochondria membranes (PubMed:29097544). PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544). In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544).|||Null animals show poor overall growth and reduced total brain volume, although the relative volume of certain regions is increased. Mutant mice demonstrate impaired hippocampal-dependent spatial memory, increased spontaneous repetitive stereotypic motor movements and decreased anxiety-like behavior compared to controls.|||The SMP-LTD domain is a barrel-like domain that binds phospholipids. http://togogenome.org/gene/10090:Tmem132c ^@ http://purl.uniprot.org/uniprot/E9QP73|||http://purl.uniprot.org/uniprot/Q8CEF9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM132 family.|||Membrane http://togogenome.org/gene/10090:Kctd7 ^@ http://purl.uniprot.org/uniprot/Q8BJK1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||High expression in brain, particularly in post-mitotic neurons. Expressed in the mitral cells of the olfactory bulbs, the hippocampus, the deep layers of the cerebral cortex and Purkinje cells of the cerebellum. Not detected in astrocytes or microglial cells. Also expressed in heart, liver, spleen and kidney.|||Interacts with CUL3.|||May be involved in the control of excitability of cortical neurons.|||cytosol http://togogenome.org/gene/10090:Clnk ^@ http://purl.uniprot.org/uniprot/Q9QZE2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An adapter protein which plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation (PubMed:10562326, PubMed:10744659, PubMed:11509653, PubMed:12681493). Together with FGR, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (PubMed:15199160, PubMed:16439675). Acts as a positive regulator of both T-cell receptor and natural killer T (NKT) cell receptor signaling in CD4-positive NKT cells (PubMed:16439675). Together with MAP4K1, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (PubMed:11509653). May be involved in tumor necrosis factor induced cell death by promoting reactive oxidative species generation, and MLKL oligomerization, ultimately leading to necrosis (PubMed:26009488). Involved in phosphorylation of LAT (PubMed:11463797). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (PubMed:12681493).|||By cytokines such as IL2 and IL3 (PubMed:10562326, PubMed:15199160, PubMed:16439675). In natural killer T cells, by alpha-galactoceramide (PubMed:16439675).|||Cytoplasm|||Expressed in T-cells, mast cells, natural killer and natural killer T cells (at protein level) (PubMed:10744659, PubMed:15199160, PubMed:16439675, PubMed:11509653). Expressed in cytokine-stimulated hemopoietic cells (PubMed:10562326).|||No visible phenotype.|||The N-terminal proline-rich region interacts with the SH3 domain of PLCG1.|||The SH2 domain is important for restoration of BCR-induced calcium response and JNK2 activation in BLNK-deficient DT40 cells expressing LAT.|||Tyrosine-phosphorylated upon BCR cross-linking (PubMed:10744659, PubMed:11463797). Tyrosine phosphorylation at both Tyr-69 and Tyr-96 are required for BCR-induced calcium response and are essential to restore PLCG2-mediated signaling in BLNK-deficient DT40 cells, but this phosphorylation is dispensable in cells expressing LAT (PubMed:10744659, PubMed:11463797). Interacts with the SH2 domain of PLCG1 via phosphorylated Tyr-96 (PubMed:10744659, PubMed:11463797). Tyrosine phosphorylation is increased when complexed with SKAP1 and FYB1 (PubMed:12681493).|||When phosphorylated, interacts with PLCG1, PLCG2, GRB2, VAV and LAT (PubMed:10744659, PubMed:11463797). Associated with a tyrosine-phosphorylated polypeptide (p92) in response to immunoreceptor stimulation (PubMed:10562326). Interacts with LBR and AGO2 (PubMed:26009488). Interacts with FGR (PubMed:16439675). Part of a complex consisting of CLNK, SKAP1 and FYB1 (PubMed:12681493). Interacts (via SH2 domain) with FYB1; this interaction allows SKAP1 and FYB1 to promote tyrosine phosphorylation of CLNK by LYN (PubMed:26009488). Interacts (via SH2 domain) with MAP4K1 (PubMed:11509653). http://togogenome.org/gene/10090:Rgs5 ^@ http://purl.uniprot.org/uniprot/O08850 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in heart and muscle.|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G(i)-alpha and G(o)-alpha, but not to G(s)-alpha.|||Membrane http://togogenome.org/gene/10090:Tpp1 ^@ http://purl.uniprot.org/uniprot/O89023 ^@ Cofactor|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing and activity (By similarity).|||Binds 1 Ca(2+) ion per subunit.|||Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:28464005). May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (By similarity). Requires substrates with an unsubstituted N-terminus (By similarity).|||Lysosome|||Melanosome|||Monomer (By similarity). Interacts with CLN5 (PubMed:19941651). Interacts with CLN3 (By similarity). http://togogenome.org/gene/10090:Eif5b ^@ http://purl.uniprot.org/uniprot/Q05D44 ^@ Cofactor|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.|||Binds 1 monovalent cation per monomer in the active site. Structural cofactor that stabilizes the GTP-bound 'on' state. May also act as a transition state stabilizer of the hydrolysis reaction.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Interacts through its C-terminal domain (CTD) with the CTD of eIF1A (EIF1AX) or with the CTD of EIF5 (mutually exclusive) through a common binding site. Interacts with eIF1A (EIF1AX) from the location of the start codon by the 43S complex until the formation of the 80S complex (By similarity). Interacts with ANXA5 in a calcium and phospholipid-dependent manner (By similarity).|||Plays a role in translation initiation. Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon. Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after formation of the 80S initiation complex. Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes. In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit. http://togogenome.org/gene/10090:Lypla1 ^@ http://purl.uniprot.org/uniprot/P97823 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS (By similarity). Has depalmitoylating activity toward KCNMA1 (By similarity). Could also depalmitoylate ADRB2 (By similarity). Acts as a lysophospholipase hydrolyzing various lysophospholipids including lysophosphatidylcholine (lyso-PC), lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-PI) and lysophosphatidylserine (lyso-PS)(PubMed:9139730). Has much higher thioesterase activity than lysophospholipase activity (By similarity). Contributes to the production of lysophosphatidic acid (LPA) during blood coagulation by recognizing and cleaving plasma phospholipids to generate lysophospholipids which in turn act as substrates for ENPP2 to produce LPA (By similarity).|||Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum|||Homodimer.|||May be due to an intron retention.|||Nucleus membrane http://togogenome.org/gene/10090:Dcaf11 ^@ http://purl.uniprot.org/uniprot/Q3TYA0|||http://purl.uniprot.org/uniprot/Q3UD98|||http://purl.uniprot.org/uniprot/Q91VU6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the WD repeat LEC14B family.|||Interacts with DDB1 and CUL4A.|||May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. http://togogenome.org/gene/10090:Bhlhe22 ^@ http://purl.uniprot.org/uniprot/Q8C6A8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain-specific, with the highest expression in the cerebellum.|||Expressed at 11.5 dpc within the neuroblast layer (NBL) of the central retina. As retinogenesis progressed from central to peripheral retina from 12 dpc to 15.5 dpc, expression expanded to the entire retina with the majority of Bhlhb5+ cells being detected in the proliferating NBL. From 17.5 dpc to birth (P0), expression became restricted to the ganglion cell layer (GCL) and to the inner boundary of the NBL (INL; inner nuclear layer), presumably the newly formed ACL (amacrine cells). Predominantly expressed in post-mitotic cells in the developing retina. Expressed from 9.5 dpc in the neural tube, restricted to longitudinal ventral columns of neurons, extending from the hindbrain to the caudal spinal cord. In the developing cortex, at 12.5 dpc, expressed in the nascent cortical plate of the dorsal telencephalon (at protein level). During peak production of deep layer neurons between 12.5 and 13.5 dpc, restricted to postmigrational neurons, with no expression in the proliferative ventricular zone (VZ) or in migrating neurons. Between 15.5 and 17.5 dpc, when superficial layer neurons are generated, strongly expressed in the cortical plate and weakly in presumptive migrating neurons and in the subventricular zone (SVZ). Does not colocalize with proliferating progenitors in S or M phase in either the VZ or the SVZ; restricted to postmitotic glutamatergic projection neurons during neurogenesis. Not detected in cortical GABAergic interneurons or their extracortical sites of genesis, the medial and caudal ganglionic eminences (at protein level). Postnatally, down-regulation begins at the junction of the cingulate cortex and neocortex; by postnatal day 4 (P4), down-regulation well into the neocortex is observed anteriorly, with the exception of the most superficial layer. At P4, expressed in neocortical layers II, III, IV, and V. Within layer VI, expressed in only very rare scattered TBR1 negative neurons. Down-regulation continues from medial to lateral, exhibiting a markedly reduced expression by P14. Expression varies strikingly along the A-P axis with a precipitous decrease in the rostral cortical plate. At 12.5 dpc, highly expressed medially in the cingulate cortex with weak expression in the rest of the cortex. At 15.5 dpc, expressed in a high caudomedial to a low rostrolateral gradient. Between 15.5dpc and P0, expression increases laterally and the gradient gradually transforms into a sharp border between the presumptive rostral motor and sensory domains. During the first postnatal week, there is a further transformation from homogeneous expression across sensory cortex into discrete areas of high expression coincident with the primary sensory areas. At P4 and P7, expressed in primary visual cortex, primary auditory cortex and distinct primary somatosensory representations, including the vibrissal barrel field. In the spinal chord, transiently expressed in V1, V2, and dI6 interneurons at 10.5 dpc. Also observed in a subpopulation of late-born neurons that migrate to the superficial layers of the dorsal horn. Expression starts shortly after the neurons exit mitosis at 13.5 dpc and persisting for up to 2 weeks postnatally. At birth, about one-third of dorsal horn neurons expressing the protein are excitatory and two-thirds inhibitory. Also expressed in the developing eye and hair follicles, in the epithelial layer of the cochlea in the developing inner, and in the nasal epithelium. At 16.5 dpc, expressed outside the CNS, in particular in all sensory organs; in the nasal pits, transcripts can be detected in the olfactory epithelium. In the developing eye it can be found in the inner and outer retinal layer, and it is also detectable in the sensory layer of the cochlea in the developing inner ear. In addition, expression is found in the developing hair follicles, both in the epithelial component and in the dermal papilla, and in the skin.|||Inhibits DNA binding of TCF3/E47 homodimers and TCF3 (E47)/NEUROD1 heterodimers and acts as a strong repressor of Neurod1 and Myod-responsive genes, probably by heterodimerization with class a basic helix-loop-helix factors. Despite the presence of an intact basic domain, does not bind to DNA (By similarity). In the brain, may function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization. May be required for the survival of a specific population of inhibitory neurons in the superficial laminae of the spinal cord dorsal horn that may regulate pruritis. Seems to play a crucial role in the retinogenesis, in the specification of amacrine and bipolar subtypes. Forms with PRDM8 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation (PubMed:22284184).|||Interacts with PRDM8.|||Nucleus|||Null mice exhibits aberrant expression of brain area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, vibrissal barrels display postsynaptic disorganization. In caudal motor cortex, anomalous differentiation of corticospinal motor neurons is observed, accompanied by failure of corticospinal tract formation. Mice also develop self-inflicted skin lesions and show significantly enhanced scratching responses to pruritic agents, due to the selective loss of a subset of spinal cord inhibitory interneurons. http://togogenome.org/gene/10090:Zdhhc9 ^@ http://purl.uniprot.org/uniprot/P59268 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with GOLGA7.|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates. The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS. May have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and therefore regulate G protein-coupled receptor signaling.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Pcdh20 ^@ http://purl.uniprot.org/uniprot/Q8BIZ0 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Potential calcium-dependent cell-adhesion protein. http://togogenome.org/gene/10090:Huwe1 ^@ http://purl.uniprot.org/uniprot/A2AFQ0|||http://purl.uniprot.org/uniprot/Q4JG03|||http://purl.uniprot.org/uniprot/Q7TMY8 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UPL family. TOM1/PTR1 subfamily.|||Cytoplasm|||E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15767685, PubMed:18488021). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (By similarity). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (By similarity). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15767685). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (By similarity). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (By similarity). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (By similarity). Mediates polyubiquitination of PA2G4 (By similarity). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (By similarity). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (By similarity).|||Expression increases during neuronal differentiation such that the cortical plate contains the highest level.|||Interacts with isoform p19ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity (By similarity). Interacts with MYCN, POLB and CDC6 (By similarity). Interacts with PA2G4 (By similarity). Interacts with NR1D1 (By similarity). Interacts with AMBRA1 (By similarity). Interacts with HAPSTR1 (By similarity). Interacts with HAPSTR2 (By similarity).|||Mitochondrion|||Nucleus|||Phosphorylated on tyrosine; phosphorylation is probably required for its ability to inhibit TP53 transactivation.|||The HECT domain mediates inhibition of the transcriptional activity of p53.|||Widely expressed. http://togogenome.org/gene/10090:Rbm26 ^@ http://purl.uniprot.org/uniprot/Q6NZN0 ^@ Developmental Stage|||Tissue Specificity ^@ Expressed in testis and ovary at 15.5 dpc.|||Expressed in testis and ovary. http://togogenome.org/gene/10090:Ext1 ^@ http://purl.uniprot.org/uniprot/P97464|||http://purl.uniprot.org/uniprot/Q3V1P4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 47 family.|||Endoplasmic reticulum membrane|||Expressed in maturing chondrocytes.|||Forms a homo/heterooligomeric complex with EXT2. Interacts with NDST1.|||Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity).|||Golgi apparatus membrane|||Initially expressed at 6.5 dpc, which coincides with gastrulation of the embryo. High level of expression in developing limb buds at 10.5 to 12.5 dpc.|||Membrane|||cis-Golgi network membrane http://togogenome.org/gene/10090:Ccdc25 ^@ http://purl.uniprot.org/uniprot/A0PK78|||http://purl.uniprot.org/uniprot/Q78PG9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC25 family.|||Cell membrane|||Endomembrane system|||In the context of cancer, mice display reduced metastase formation, without affecting primary tumor growth.|||Interacts (via cytoplasmic region) with ILK.|||Transmembrane receptor that senses neutrophil extracellular traps (NETs) and triggers the ILK-PARVB pathway to enhance cell motility. NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Formation of NETs is also associated with cancer metastasis, NET-DNA acting as a chemotactic factor to attract cancer cells (By similarity). Specifically binds NETs on its extracellular region, in particular the 8-OHdG-enriched DNA present in NETs, and recruits ILK, initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells (By similarity). In the context of cancer, promotes cancer metastasis by sensing NETs and promoting migration of tumor cells (By similarity). http://togogenome.org/gene/10090:Slfn14 ^@ http://purl.uniprot.org/uniprot/V9GXG1 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with ribosomes in an ATP-independent manner (PubMed:25996083).|||C-terminally truncated SLFN14 endoribonuclease: Requires manganese and magnesium for its endoribonuclease activity.|||Displays polysome-associated endoribonuclease activity towards mRNAs and rRNAs (PubMed:25996083). May play a role in RNA surveillance pathways by recognizing stalled ribosomes and triggering endonucleolytic cleavage of aberrant mRNAs (Probable). Cleaves different types of rRNAs and mRNAs in a magnesium- and manganese-dependent and ATP-independent manner. Involved in correct maturation of megakaryocytes and especially important for proplatelet extension (By similarity).|||Expressed in spleen (PubMed:19619625).|||Nucleus|||Shows no ribosome-associated and endoribonuclease activities. http://togogenome.org/gene/10090:Spock1 ^@ http://purl.uniprot.org/uniprot/B2RXY1|||http://purl.uniprot.org/uniprot/Q6DIC9|||http://purl.uniprot.org/uniprot/Q8BKQ3 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Nck1 ^@ http://purl.uniprot.org/uniprot/Q99M51 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA (By similarity).|||Associates with BLNK, PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with SOCS7. This interaction is required for nuclear import. Part of a complex containing PPP1R15B, PP1 and NCK1. Interacts with RALGPS1. Interacts with CAV2 (tyrosine phosphorylated form). Interacts with ADAM15. Interacts with FASLG. Directly interacts with RASA1. Interacts with MINK1. Interacts with KDR (tyrosine phosphorylated). Interacts (via SH2 domain) with EPHB1; activates the JUN cascade to regulate cell adhesion. Interacts with EPHA2. Interacts (via SH2 domain) with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain and SH3 domain 2) with EGFR. Interacts with PAK1 and SOS1. Interacts (via SH3 domains) with PKN2 (By similarity). Interacts with FLT1 (tyrosine phosphorylated). Interacts with the inactive form of EIF2AK2/PKR (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Nucleus|||Only the first and third SH3 domains seem to be involved in RASA1-binding; the second SH3 domain and the SH2 domains do not seem to be involved.|||Phosphorylated on Ser and Tyr residues. Phosphorylated in response to activation of EGFR and FcERI. Phosphorylated by activated PDGFRB (By similarity). http://togogenome.org/gene/10090:Dus4l ^@ http://purl.uniprot.org/uniprot/A0A0R4J016|||http://purl.uniprot.org/uniprot/Q32M08 ^@ Function|||Similarity ^@ Belongs to the Dus family. Dus4 subfamily.|||Belongs to the dus family.|||Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs. http://togogenome.org/gene/10090:Or5b116 ^@ http://purl.uniprot.org/uniprot/F6QVZ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rab18 ^@ http://purl.uniprot.org/uniprot/A0A3Q4EI12|||http://purl.uniprot.org/uniprot/P35293|||http://purl.uniprot.org/uniprot/Q0PD38 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expression is high in the brain, moderate in the pituitary, and low in the liver. Detected in all tissues. Highly enriched on apical endocytic structures in polarized epithelial cells of kidney proximal tubules. Detected on both the apical and basolateral domains in epithelial cells of the intestine.|||Interacts (in GTP-bound form) with ZFYVE1 (By similarity). Interacts with ZW10 and this interaction is enhanced in the presence of ZFYVE1 (By similarity). Interacts with BSCL2 (By similarity).|||Lipid droplet|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (By similarity). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). Required for the localization of ZFYVE1 to lipid droplets and for its function in mediating the formation of endoplasmic reticulum-lipid droplets (ER-LD) contacts (By similarity). Also required for maintaining endoplasmic reticulum structure (By similarity). Plays a role in apical endocytosis/recycling (PubMed:7706395). Plays a key role in eye and brain development and neurodegeneration (By similarity). http://togogenome.org/gene/10090:Lax1 ^@ http://purl.uniprot.org/uniprot/Q8BHB3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in T-cells and B-cells.|||Mice are viable, fertile and healthy, and show normal lymphocyte development. However, their T- and B-cells are hyperresponsive to stimulation via TCR or BCR.|||Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and BCR (B-cell antigen receptor)-mediated signaling in B-cells.|||Phosphorylated on tyrosines upon TCR or BCR activation; which leads to the recruitment of GRB2, PIK3R1 and GRAP2.|||Up-regulated in T- and B-cells following TCR and BCR engagement, respectively.|||When phosphorylated, interacts with GRB2, PIK3R1 and GRAP2. http://togogenome.org/gene/10090:Nts ^@ http://purl.uniprot.org/uniprot/Q9D3P9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the neurotensin family.|||Interacts with NTSR1. Interacts with SORT1. Interacts with SORL1.|||Neurotensin is cleaved and degraded by Angiotensin-converting enzyme (ACE) and neprilysin (MME).|||Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle (By similarity).|||Secreted|||secretory vesicle http://togogenome.org/gene/10090:Pglyrp1 ^@ http://purl.uniprot.org/uniprot/O88593|||http://purl.uniprot.org/uniprot/Q4FK86 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.|||Cytoplasm|||Homodimer; disulfide-linked. Interacts with HSPA1A; this interaction forms a cytotoxic complex that is released by lymphokine-activated killer cells (PubMed:14585845). Interacts with HSPBP1; this interaction blocks the cytotoxic activity of the PGLYRP1-HSPA1A complex (PubMed:14585845).|||Innate immunity protein that plays several important functions in antimicrobial and antitumor defense systems.|||Innate immunity protein that plays several important functions in antimicrobial and antitumor defense systems. Acts as a pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria and thus provides bactericidal activity (PubMed:9707603, PubMed:9660837, PubMed:12649138). Forms an equimolar complex with heat shock protein HSPA1A and induces programmed cell death through apoptosis and necroptosis in tumor cell lines by activating the TNFR1 receptor on the target cell membrane (PubMed:14585845). In addition, acts in complex with the Ca(2+)-binding protein S100A4 as a chemoattractant able to induce lymphocyte movement. Mechanistically, this complex acts as a ligand of the chemotactic receptors CCR5 and CXCR3 which are present on the cells of the immune system. Promotes also the activation of lymphocytes that become able to kill virus-infected cells as well as tumor cells by modulating the spectrum of their target-cell specificity. Induction of cytotoxicity on monocyte surface requires interaction with TREM1 receptor (By similarity).|||Secreted|||Strongly expressed in spleen and lung. Also detected in brain and thymus. In the lung, expressed in the intraalveolar space, in the brain, expressed in the Purkinje cells of the cerebellum and in certain layers of neurons in the hippocampus. Also detected in cells filling the space within the intestinal villus. http://togogenome.org/gene/10090:Rad21l ^@ http://purl.uniprot.org/uniprot/A2AU37 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rad21 family.|||Chromosome|||Component of some meiotic cohesin complex composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their hinge domain, RAD21L which link them, and STAG3.|||Male mice are sterile due to defects in chromosome synapsis at prophase I, leading to an arrest at a zygotene-like stage leading to total azoospermia. Females are fertile but develop an age-dependent sterility.|||Meiosis-specific component of some cohesin complex required during the initial steps of prophase I in male meiosis. Probably required during early meiosis in males for separation of sister chromatids and homologous chromosomes. Replaces RAD21 in premeiotic S phase (during early stages of prophase I), while RAD21 reappears in later stages of prophase I. Involved in synaptonemal complex assembly, synapsis initiation and crossover recombination between homologous chromosomes during prophase I. Not required for meiosis in females in young mice, while it is required later as mice age.|||Nucleus|||Specifically expressed in male and female gonads (at protein level). http://togogenome.org/gene/10090:Htr1d ^@ http://purl.uniprot.org/uniprot/Q61224 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in the motor column in spinal cord, and in several cranial motor nuclei, including nucleus ambiguous, oculomotoris, trochelaris and abducens. Detected in gamma motor neurons in the lumbar spinal cord. Detected in proprioceptive sensory neurons in dorsal root ganglia.|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.|||Homodimer. Heterodimer with HTR1B (By similarity).|||No visible phenotype. Depending on the task, mutant mice show improved motor coordination, especially in avoiding hind limb slips when crossing a narrow beam and in climbing onto a horizontal hanging wire. http://togogenome.org/gene/10090:Crocc ^@ http://purl.uniprot.org/uniprot/Q8CJ40 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the rootletin family.|||Highest expression detected in photoreceptor cells of retina. Expressed at lower levels in brain, trachea and kidney. Detected in all major ciliated epithelia. During embryonic development, enriched along the apical domains of neuroepithelium in brain ventricular zone, in primordia of retinal pigment epithelia and in neural retina.|||Homomer. Interacts with KLC3, NEK2 and the N-terminus of CEP250 (PubMed:12427867, PubMed:16339073). Interacts with CEP44 (By similarity).|||Major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus (PubMed:12427867). Furthermore, is required for the correct positioning of the cilium basal body relative to the cell nucleus, to allow for ciliogenesis (By similarity). Contributes to centrosome cohesion before mitosis (By similarity).|||Mice have no ciliary rootlets in ciliated cells.|||Phosphorylated by NEK2 which may regulate its association with centrosomes.|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Hsd3b6 ^@ http://purl.uniprot.org/uniprot/O35469|||http://purl.uniprot.org/uniprot/Q7TPU0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. May be involved in local production of progesterone.|||Belongs to the 3-beta-HSD family.|||Earliest isoform to be expressed during embryogenesis in cells of embryonic origin at 7 and 9.5 dpc, and is the major isoform expressed in uterine tissue at the time of implantation (4.5 dpc) and continues to be expressed in uterine tissue at 6.5, 7.5 and 9.5 dpc. It is expressed in giant trophoblasts at 9.5 dpc and is expressed in the placenta through 15.5 dpc.|||Endoplasmic reticulum membrane|||Expressed in skin and testis.|||Mitochondrion membrane http://togogenome.org/gene/10090:A1bg ^@ http://purl.uniprot.org/uniprot/Q19LI2 ^@ Developmental Stage|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed at 3-days but not at 11-days of age in both female and male GH transgenic mice. Expression in the normal female mice begins as early as 2 months and is detected at much higher levels at 5, 12 and 24 months while at 30 months, expression is lower.|||Expressed in the liver hepatocytes of male and female GH transgenic mice and in the liver of female, but not of male, non-transgenic mice.|||Induced in hepatocytes during the proliferative phase of liver regeneration. Induction requires a continuous pattern of GH (growth hormaone) secretion and an intact GH-GH receptor-signaling complex.|||Interacts with CRISP3.|||Secreted http://togogenome.org/gene/10090:Dpcd ^@ http://purl.uniprot.org/uniprot/Q8BPA8 ^@ Function|||Similarity ^@ Belongs to the DPCD family.|||May play a role in the formation or function of ciliated cells. http://togogenome.org/gene/10090:Sanbr ^@ http://purl.uniprot.org/uniprot/Q68FF0 ^@ Domain|||Function|||Similarity|||Subunit ^@ Belongs to the KIAA1841 family.|||Homodimer (PubMed:33831416). Interacts (via the BTB domain) with HDAC1 and NCOR2 (PubMed:33831416).|||Negatively regulates class switch recombination or isotype switching in splenic B-cells.|||The BTB domain is important for homodimerization and for its function in negative regulation of class switch recombination. http://togogenome.org/gene/10090:Cipc ^@ http://purl.uniprot.org/uniprot/Q8R0W1 ^@ Caution|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the heart, kidney and liver and shows a circadian oscillation in these tissues with a peak at circadian time 14 hours (at protein level). Expressed in the brain, including the suprachiasmatic nucleus (SCN) of the brain, and in multiple peripheral tissues such as heart, liver and kidney. Exhibits a circadian oscillation in the peripheral tissues with a peak at circadian time 14 hours.|||Interacts with CLOCK. Forms a ternary complex with the CLOCK-BMAL1 heterodimer. Interacts with CAD and HSPA5 (By similarity).|||It is uncertain whether Met-1 or Met-36 is the initiator.|||No visible phenotype. Knockout mice display normal locomotor activity rhythms and normal behavioral responses to light. Animals show reduction liver PER1 peak levels, but no change in the expression of other core clock genes.|||Nucleus|||Transcriptional repressor which may act as a negative-feedback regulator of CLOCK-BMAL1 transcriptional activity in the circadian-clock mechanism. May stimulate BMAL1-dependent phosphorylation of CLOCK (PubMed:17310242, PubMed:19414601). However, the physiogical relevance of these observations is unsure, since experiments in knockout mice showed that CIPC is not critially required for basic circadian clock (PubMed:25862660).|||cytosol http://togogenome.org/gene/10090:Eri1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0C8|||http://purl.uniprot.org/uniprot/Q7TMF2 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it can bind simultaneously with SLBP to the 3'-end of histone mRNA, the presence of SLBP prevents the exonuclease activity.|||Binds 2 magnesium ions per subunit.|||Cytoplasm|||High neonatal mortality rate. Reduced body size in surviving mice which is observed as early as embryonic day 15.5 and remains significant in adults.|||Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Binds to 40S and 60S ribosomal subunits and to 80S assembled ribosomes. Interacts in a cooperative manner with SLBP to the mature 3'-end of histone mRNAs. Found in a ternary complex with SLBP and the stem-loop structure of the 3'-end of histone mRNAs (By similarity).|||Nucleus|||RNA exonuclease that binds to the 3'-end of histone mRNAs and degrades them, suggesting that it plays an essential role in histone mRNA decay after replication. A 2' and 3'-hydroxyl groups at the last nucleotide of the histone 3'-end is required for efficient degradation of RNA substrates. Also able to degrade the 3'-overhangs of short interfering RNAs (siRNAs) in vitro, suggesting a possible role as regulator of RNA interference (RNAi). Required for binding the 5'-ACCCA-3' sequence present in stem-loop structure. Able to bind other mRNAs (By similarity). Required for 5.8S rRNA 3'-end processing. Also binds to 5.8s ribosomal RNA (PubMed:18438418). Binds with high affinity to the stem-loop structure of replication-dependent histone pre-mRNAs. In vitro, does not have sequence specificity. In vitro, has weak DNA exonuclease activity. In vitro, shows biphasic kinetics such that there is rapid hydrolysis of the last three unpaired RNA nucleotides in the 39 flanking sequence followed by a much slower cleavage through the stem that occurs over a longer incubation period in the order of hours (By similarity).|||The SAP domain is necessary for binding to the stem-loop structure of histone mRNAs and to form the ternary complex with SLBP, but not for 3'-end histone mRNA exonuclease activity.|||Widely expressed with high levels in spleen, thymus and testis (at protein level).|||nucleolus http://togogenome.org/gene/10090:Tnfrsf9 ^@ http://purl.uniprot.org/uniprot/P20334 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in activated thymocytes, splenic T cells, CD4(+), and CD8(+) T-cells.|||Predominantly homodimeric, but may also exist as a monomer (PubMed:7678621). Associates with p56-LCK. Interacts with TRAF1, TRAF2 and TRAF3 (By similarity).|||Receptor for TNFSF9/4-1BBL. Conveys a signal that enhances CD8(+) T-cell survival, cytotoxicity, and mitochondrial activity, thereby promoting immunity against viruses and tumors (By similarity).|||Up-regulated after cell treatment by PMA and ionomycin, suggesting that optimal expression requires both protein kinase C activation and increase in intracellular calcium. http://togogenome.org/gene/10090:Laptm4a ^@ http://purl.uniprot.org/uniprot/Q8BG66 ^@ Similarity ^@ Belongs to the LAPTM4/LAPTM5 transporter family. http://togogenome.org/gene/10090:Or14j8 ^@ http://purl.uniprot.org/uniprot/Q7TRJ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbck1 ^@ http://purl.uniprot.org/uniprot/Q9WUB0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subunit ^@ Auto-ubiquitinated. Auto-ubiquitination leads to degradation by the proteasome (By similarity).|||Belongs to the RBR family.|||Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31. LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits (By similarity). Interacts with beta-I-type (PRKCB1) and zeta-type protein kinase C (PRKCZ) (By similarity). Interacts with UBE2L3 (PubMed:10431818). Interacts with IREB2 only in iron-rich conditions. Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner. Interacts with EYA1, TAB2, TAB3, MAP3K7 TRAF6 and RIPK1 (PubMed:20956555). Interacts with IRF3 (By similarity).|||E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria. LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin. The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation. Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types.|||Impaired TNF-alpha-mediated NF-kappa-B activation and enhanced JNK-mediated apoptosis.|||Phosphorylated. In vitro, phosphorylation inhibits auto-ubiquitination activity (By similarity).|||The RanBP2-type zinc finger, also called Npl4 zinc finger (NZF), mediates binding to 'Met-1'-linked polyubiquitins.|||The UBL domain mediates association with RNF31 via interaction with its UBA domain. http://togogenome.org/gene/10090:Chrm5 ^@ http://purl.uniprot.org/uniprot/Q920H4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM5 sub-subfamily.|||Cell membrane|||Postsynaptic cell membrane|||The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover (By similarity). http://togogenome.org/gene/10090:Frey1 ^@ http://purl.uniprot.org/uniprot/Q8CF31 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Expressed in round spermatids (at protein level).|||Expressed in round spermatids belonging to stages V to VII/VIII with no visible expression in earlier or later stages.|||Interacts with SPPL2C (via active sites); the interaction stabilizes FREY1 protein and inhibits SPPL2C proteolytic activity (PubMed:35960805). Interacts with IZUMO1; the interaction retains IZUMO1 at the endoplasmic reticulum membrane and coordinates IZUMO1 complex assembly (PubMed:35960805).|||Key regulator for male fertility expressed transiently in round spermatids where it recruits IZUMO1 at the endoplasmic reticulum (ER) membrane and coordinates the oolemmal binding multimeric complex (IZUMO1 complex) assembly. Upon complete assembly of the IZUMO1 complex, its ER retention is released, facilitating IZUMO1 complex export to the acrosome (PubMed:35960805, PubMed:36050562). Through the interaction with SPPL2C, inhibits its intramembrane protease activity directly accessing the catalytic center of an I-CLiP (PubMed:35960805).|||Mutant males are normozoospermic infertile (PubMed:35960805, PubMed:36050562). Mutant males neither have significant differences in testis/body weight ratios nor testicular morphology. They do not show any alteration in basic sperm motility (PubMed:35960805). Sperm from mutant males passes through the zona pellucida, but fails to bind to the oocyte membrane and accumulates in the perivitelline space (PubMed:36050562). FREY1 and SPPL2C double knockout mice are normozoospermic infertile (PubMed:35960805). http://togogenome.org/gene/10090:Smok3b ^@ http://purl.uniprot.org/uniprot/C0HKC8|||http://purl.uniprot.org/uniprot/C0HKC9 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Smok subfamily.|||May play a role in sperm motility, especially in the regulation of flagellar function.|||Testis-specific. Expressed in the testis from 22 days postpartum (22 dpp). http://togogenome.org/gene/10090:Tbcel ^@ http://purl.uniprot.org/uniprot/Q8C5W3 ^@ Function|||Subcellular Location Annotation ^@ Acts as a regulator of tubulin stability.|||cytoskeleton http://togogenome.org/gene/10090:Smarcc1 ^@ http://purl.uniprot.org/uniprot/P97496 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SMARCC family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3 (By similarity). Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:22952240, PubMed:26601204). Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). May also interact with the SIN3A histone deacetylase transcription repressor complex in conjunction with SMARCA2 and SMARCA4. The minimal complex composed of SMARCC1 and SMARCA4 seems to be able to associate with cyclin such as CCNE1 or transcription factors such as KLF1 or GATA1. Interacts with NR3C1 and SMARD1. Interacts with TRIP12; leading to disrupt interaction between TRIP12 and SMARCE1 and prevent SMARCE1 ubiquitination (By similarity). Interacts with CEBPB (when not methylated) (PubMed:20111005). Interacts with KDM6B (PubMed:21095589). Interacts with MKKS; the interaction takes place predominantly in the cytoplasm and may modulate SMARCC1 location (By similarity). Interacts with DPF2 (By similarity). Interacts with PRDM1/BLIMP1 (By similarity). Interacts with DPF3a (isoform 2 of DPF3/BAF45C) and with HDGFL2 in a DPF3a-dependent manner (By similarity).|||Cytoplasm|||Highly expressed in adult brain, testis and thymus.|||Highly expressed in all organs except heart and liver (12.5 dpc and 14.5 dpc). The level of expression gradually diminishes as embryos develop, with expression restricted mostly to the CNS and thymus at 18.5 dpc. Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5 dpc-16.5 dpc.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. May stimulate the ATPase activity of the catalytic subunit of the complex. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.|||Nucleus http://togogenome.org/gene/10090:Cdk11b ^@ http://purl.uniprot.org/uniprot/A2A9P6|||http://purl.uniprot.org/uniprot/P24788 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||May interact PAK1 and RANBP9. p110C interacts with RNPS1. Interacts with CCND3. Interacts with CCNL1 and CCNL2. Forms complexes with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 AND SRSF7/SLU7.|||Phosphorylation at Ser-115 creates a binding site for 14-3-3 proteins.|||Phosphorylation at Thr-437 or Tyr-438 inactivates the enzyme, while phosphorylation at Thr-584 activates it.|||Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. May act as a negative regulator of normal cell cycle progression. http://togogenome.org/gene/10090:Hao1 ^@ http://purl.uniprot.org/uniprot/Q3UEE8|||http://purl.uniprot.org/uniprot/Q9WU19 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.|||Broad substrate specificity (S)-2-hydroxy-acid oxidase that preferentially oxidizes glycolate (PubMed:9891009). The glyoxylate produced by the oxidation of glycolate can then be utilized by alanine-glyoxylate aminotransferase for the peroxisomal synthesis of glycine; this pathway appears to be an important step for the detoxification of glyoxylate which, if allowed to accumulate, may be metabolized to oxalate with formation of kidney stones (By similarity). Can also catalyze the oxidation glyoxylate, and long chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate (By similarity). Active in vitro with the artificial electron acceptor 2,6-dichlorophenolindophenol (DCIP), but O2 is believed to be the physiological electron acceptor, leading to the production of H2O2 (PubMed:9891009).|||Homotetramer.|||Liver.|||Peroxisome matrix http://togogenome.org/gene/10090:Ifi27l2a ^@ http://purl.uniprot.org/uniprot/Q8R412 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IFI6/IFI27 family.|||Homodimer (By similarity). Interacts with SKP2 (By similarity). Interacts with NR4A1 (By similarity). May interact with BCL2 (By similarity).|||Homozygous knockout mice exhibit no obvious phenotype, having normal growth rates, survival, fertility and litter sizes (PubMed:22427340). No organ pathology is detected (PubMed:22427340). However, they display decreased restenosis, the narrowing of blood vessels, upon vascular injury (PubMed:22427340).|||May be involved in the interferon-induced negative regulation of the transcriptional activity of NR4A1, NR4A2 and NR4A3 through the enhancement of XPO1-mediated nuclear export of these nuclear receptors (PubMed:22427340). Through the regulation of NR4A1 transcriptional activity, may play a role in the vascular response to injury (PubMed:22427340).|||Nucleus inner membrane|||Up-regulated by interferon (PubMed:22427340). Up-regulated by vascular tissues injury (PubMed:22427340). http://togogenome.org/gene/10090:Sult1a1 ^@ http://purl.uniprot.org/uniprot/E9QNL5|||http://purl.uniprot.org/uniprot/Q91W19 ^@ Similarity ^@ Belongs to the sulfotransferase 1 family. http://togogenome.org/gene/10090:Lrfn4 ^@ http://purl.uniprot.org/uniprot/Q80XU8 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRFN family.|||Can form heteromeric complexes with LRFN1, LRFN2, LRFN3 and LRFN5. Unable to form homophilic interactions across cell junctions. Interacts with DLG1, DLG2 and DLG3 (By similarity). Also interacts with DLG4.|||Expressed in brain and testis. In the brain, weak, but broad expression in the cerebral cortex and diencephalic nuclei. Also detected in other parts of the central nervous system, including the olfactory bulb, pons, cerebellum, and medulla oblongata, as well as in the peripheral nervous system, such as the ganglia of cranial nerves and the dorsal root ganglion during gestation.|||Glycosylated.|||Low expression from 4.5 dpc onwards. Expression increases at 10.5 dpc and decreases after 15.5 dpc. At 11.5 dpc, broadly expressed in the telencephalic and diencephalic vesicles. This pattern of expression continues until 17.5 dpc.|||Membrane|||Promotes neurite outgrowth in hippocampal neurons. May play a role in redistributing DLG4 to the cell periphery.|||The PDZ-binding motif is required for neurite outgrowth promotion. This motif is also involved in DLG1-, DLG3- and DLG4-binding (By similarity). http://togogenome.org/gene/10090:Mup15 ^@ http://purl.uniprot.org/uniprot/A9R9W0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Eral1 ^@ http://purl.uniprot.org/uniprot/Q9CZU4|||http://purl.uniprot.org/uniprot/Q9ESC5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Era GTPase family.|||Membrane|||Mitochondrion inner membrane|||Mitochondrion matrix|||Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly (By similarity).|||Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly. http://togogenome.org/gene/10090:Or51r1 ^@ http://purl.uniprot.org/uniprot/E9Q544 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxo32 ^@ http://purl.uniprot.org/uniprot/Q9CPU7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO32) formed of CUL1, SKP1, RBX1 and FBXO32.|||Specifically expressed in cardiac and skeletal muscle.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins during skeletal muscle atrophy. Recognizes TERF1 (By similarity). http://togogenome.org/gene/10090:Gpaa1 ^@ http://purl.uniprot.org/uniprot/Q9WTK3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the GPI transamidase complex, necessary for transfer of GPI to proteins (By similarity). Essential for GPI-anchoring of precursor proteins but not for GPI synthesis. Acts before or during formation of the carbonyl intermediate.|||Endoplasmic reticulum membrane|||Forms a complex with PIGK/GPI8, PIGT, PIGU and PIGS.|||Ubiquitously expressed in fetal and adult tissues. Expressed at higher levels in fetal tissues than adult tissues. In embryos abundant in the choroid plexus, skeletal muscle,. http://togogenome.org/gene/10090:Or4c15 ^@ http://purl.uniprot.org/uniprot/Q7TR09 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arr3 ^@ http://purl.uniprot.org/uniprot/Q9EQP6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 11 (P11) expressed in the soma and photoreceptor processes of the retinal inner segment, outer segment, outer plexiform layer, and inner plexiform layer. Expression in the inner plexiform layer is lost at P22.|||Belongs to the arrestin family.|||Homodimer; disulfide-linked in response to retinal illumination (By similarity). Interacts with CXCR4; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and modulates the calcium ion mobilization activity of CXCR4 (By similarity).|||Inner and outer segments, and the inner plexiform regions of the retina.|||May play a role in an as yet undefined retina-specific signal transduction. Could bind to photoactivated-phosphorylated red/green opsins.|||Photoreceptor inner segment|||photoreceptor outer segment http://togogenome.org/gene/10090:Kcnj10 ^@ http://purl.uniprot.org/uniprot/Q56VN0|||http://purl.uniprot.org/uniprot/Q8C7Z5|||http://purl.uniprot.org/uniprot/Q9JM63 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.|||Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ10 subfamily.|||Heterodimer with Kir5.1/KCNJ16; this interaction is required for KCNJ16 localization to the basolateral membrane in kidney cells. Interacts with MAGI1, alone and possibly as a heterodimer with KCNJ16; this interaction may facilitate KCNJ10/KCNJ16 potassium channel expression at the basolateral membrane in kidney cells (By similarity). Interacts with PATJ (PubMed:9647694).|||May be responsible for potassium buffering action of glial cells in the brain. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity). In the kidney, together with KCNJ16, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules (By similarity).|||Membrane|||Widely expressed in adult brain, including in the neocortex, the stratum pyrimadale of the hippocampus and the piriform cortex. Expressed by cultured astrocytes and also by cocultured cortical neurons (at protein level). Expressed in the distal segment of the nephron (PubMed:33811157). http://togogenome.org/gene/10090:Gm13276 ^@ http://purl.uniprot.org/uniprot/A0A087WR18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Spacdr ^@ http://purl.uniprot.org/uniprot/Q9EQN3 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TSC-22/Dip/Bun family.|||Binds DNA and acts as a transcriptional repressor (PubMed:27827363). Involved in the regulation of systematic glucose homeostasis and insulin sensitivity, via transcriptional repression of downstream insulin signaling targets such as OBP2A/LCN13 (PubMed:27827363). Acts as a negative regulator of lipogenic gene expression in hepatocytes and thereby mediates the control of very low-density lipoprotein release (PubMed:23307490). May play a role in neurite elongation and survival (PubMed:20878296).|||Cytoplasm|||Expressed in the liver (at protein level) (PubMed:23307490, PubMed:27827363). Expressed in Purkinje cells and proliferating cerebellar granular neurons (at protein level) (PubMed:20878296). Expressed in the cortex, medulla and papilla of the kidney.|||Expression starts at 8.5 dpc and undergoes a second peak of activation at 12.5 dpc (PubMed:11707329). At 12.5 dpc, expression encompasses the entire central nervous system, with highest levels in the dorsal root and trigeminal ganglia (PubMed:11707329). Expressed in the granule neurons and Purkinje cells in the external and internal granular layers of the cerebellum from postnatal day 6 (PubMed:20878296).|||Forms a homodimer or heterodimer (By similarity). Forms a heterodimer with TSC22D1 isoforms 1 and 2 (By similarity). Interacts with NRBP1 (By similarity).|||Induced by TGF-beta treatment (PubMed:11707329). Induced by a wasting-associated liver metabolism as a result of a methionine-choline deficient diet or cancer-induced cachectic phenotype (PubMed:23307490). Induced by renal hyperosmotic stress (PubMed:17147695).|||Involved in the development of hyperglycaemia and insulin resistance in diabetic mouse models (PubMed:27827363). May be involved in altered hepatic lipid handling as part of cancer-induced cachexia (PubMed:23307490).|||Nucleus|||Synapse|||dendrite http://togogenome.org/gene/10090:Pla2g2c ^@ http://purl.uniprot.org/uniprot/A2APR1|||http://purl.uniprot.org/uniprot/P48076 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Expressed mainly in pachytene and secondary spermatocytes and round spermatids and predominates in stage VI-VII tubules.|||PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Testis PA2 may be important in the production of prostaglandins, by the release of arachidonic acid, which in turn are necessary for the contractions of the seminiferous tubules and the testicular capsule; they also seem to decrease sperm transit time through the male reproductive tract.|||Secreted|||Testis specific. http://togogenome.org/gene/10090:Tektip1 ^@ http://purl.uniprot.org/uniprot/A6H6Q4 ^@ Function|||Subcellular Location Annotation ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Located at the center of the tektin bundle where may function to recruit tektins or stabilize the bundle.|||cilium axoneme http://togogenome.org/gene/10090:Or11a4 ^@ http://purl.uniprot.org/uniprot/Q8VFE3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Edem2 ^@ http://purl.uniprot.org/uniprot/Q8BJT9 ^@ Caution|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 47 family.|||Endoplasmic reticulum lumen|||Has similarity to alpha 1,2-mannosidases, but the catalytic activity of this protein is controversial. One study shows that it is important for a specific oligosaccharide trimming step from Man9GlcNAc2 to Man8GlcNAc2, suggesting activity as a mannosidase. However, another study reports that this protein has no mannosidase activity.|||Involved in the endoplasmic reticulum-associated degradation (ERAD) pathway that targets misfolded glycoproteins for degradation in an N-glycan-dependent manner (PubMed:15579471, PubMed:25655076). May initiate ERAD by promoting the first mannose trimming step of ERAD substrates, from Man9GlcNAc2 to Man8GlcNAc2 (By similarity). Seems to recognize and bind to exposed hydrophobic regions in target proteins (PubMed:25655076).|||N-glycosylated.|||Up-regulated by the unfolded protein response (UPR) via the XBP1 transcription factor. http://togogenome.org/gene/10090:Or5b119 ^@ http://purl.uniprot.org/uniprot/Q8VEV6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gnb1 ^@ http://purl.uniprot.org/uniprot/P62874|||http://purl.uniprot.org/uniprot/Q3TQ70 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the WD repeat G protein beta family.|||G proteins are composed of 3 units, alpha, beta and gamma (By similarity). The heterodimer formed by GNB1 and GNG2 interacts with ARHGEF5 (By similarity). The heterodimer formed by GNB1 and GNG2 interacts with GRK2 (By similarity). Forms a complex with GNAO1 and GNG3. Interacts with ARHGEF18 and RASD2 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity).|||Phosphorylation at His-266 by NDKB contributes to G protein activation by increasing the high energetic phosphate transfer onto GDP. http://togogenome.org/gene/10090:Dgcr6 ^@ http://purl.uniprot.org/uniprot/D3Z558|||http://purl.uniprot.org/uniprot/E9QP31|||http://purl.uniprot.org/uniprot/O35347|||http://purl.uniprot.org/uniprot/Q3TV71 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the gonadal family.|||Expressed in all the examined tissues with highest expression in testis.|||Expressed in early embryogenesis. Found in the peripheral and central nervous systems.|||May have a role in early embryogenesis. http://togogenome.org/gene/10090:Sh3bp4 ^@ http://purl.uniprot.org/uniprot/Q921I6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homodimer or homooligomer. Interacts with DNM2, EPS15, clathrin, the adapter protein complex 2/AP-2 and TFRC. Interacts with the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD; the interaction is most probably direct, preferentially occurs with their inactive GDP-bound form and is negatively regulated by amino acids (By similarity).|||May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy (By similarity).|||Nucleus|||Phosphorylated upon EGF stimulation. Phosphorylation prevents interaction with DNM2 (By similarity).|||The SH3 domain mediates localization to the clathrin-coated pits and vesicles. The SH3 domain mediates interaction with DNM2 and the cytoplasmic part of TFRC with a lower affinity. The SH3 domain also mediates interaction with RRAGB, RRAGC and is required for the negative regulation of mTORC1 (By similarity).|||clathrin-coated pit|||clathrin-coated vesicle http://togogenome.org/gene/10090:Ube2z ^@ http://purl.uniprot.org/uniprot/Q3UE37 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Catalyzes the covalent attachment of ubiquitin to other proteins. Specific substrate for UBA6, not charged with ubiquitin by UBE1. May be involved in apoptosis regulation.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Spin2c ^@ http://purl.uniprot.org/uniprot/Q6NVE3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPIN/STSY family.|||Interacts with C11orf84/SPINDOC.|||May be involved in the regulation of cell cycle progression. Exhibits H3K4me3-binding activity.|||Nucleus http://togogenome.org/gene/10090:Or5m10b ^@ http://purl.uniprot.org/uniprot/L7MTT3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Setd7 ^@ http://purl.uniprot.org/uniprot/Q8VHL1 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET7 subfamily.|||Chromosome|||Expressed during all pre-implementation stages in both male and female embryos.|||Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3 (By similarity). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). Plays a central role in the transcriptional activation of genes such as collagenase or insulin (PubMed:12711597). Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription (By similarity). Has also methyltransferase activity toward non-histone proteins such as CGAS, p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins (PubMed:35210392). Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II (By similarity). Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation (By similarity). Monomethylates 'Lys-491' of CGAS, promoting interaction between SGF29 and CGAS (PubMed:35210392).|||Interacts with IPF1/PDX-1.|||Nucleus|||The SET domain is necessary but not sufficient for histone methyltransferase activity. http://togogenome.org/gene/10090:Vars2 ^@ http://purl.uniprot.org/uniprot/Q3U2A8 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Mitochondrion|||The sequence differs from that shown because it seems to be derived from a pre-mRNA. http://togogenome.org/gene/10090:Hesx1 ^@ http://purl.uniprot.org/uniprot/Q61658 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ANF homeobox family.|||Can form heterodimers with PROP1 in binding to DNA Interacts with TLE1.|||Down-regulated during embryonic stem (ES) cell differentiation.|||Early expression seen in the anterior midline endoderm and prechordal plate precursor, subsequently activated in the overlying ectoderm of the cephalic neural plate. Later disappears in the mesendoderm while remaining in the prospective prosencephalic region of the neural plate ectoderm, ultimately expression is restricted to Rathke pouch, the primordium of the pituitary. Expressed in embryonic stem cells.|||High levels found in the embryonic liver, lower level expression seen in the viscera, amnion and yolk sac.|||Nucleus|||Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation. http://togogenome.org/gene/10090:Sgsh ^@ http://purl.uniprot.org/uniprot/Q3URR4|||http://purl.uniprot.org/uniprot/Q9EQ08 ^@ Similarity ^@ Belongs to the sulfatase family. http://togogenome.org/gene/10090:Ifi35 ^@ http://purl.uniprot.org/uniprot/Q9D8C4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a signaling pathway regulator involved in innate immune system response (PubMed:29350881). In response to interferon IFN-alpha, associates in a complex with transcriptional regulator NMI to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 and correlates with IFI35 dephosphorylation (By similarity). In complex with NMI, inhibits virus-triggered type I interferon/IFN-beta production (By similarity). In complex with NMI, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of the NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries (PubMed:29350881). Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation when actively released by macrophage to the extracellular space during cell injury and pathogen invasion (By similarity). Macrophage-secreted IFI35 activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines (By similarity).|||Belongs to the NMI family.|||Cytoplasm|||Homodimer. Also interacts with B-ATF. Interacts with TRIM21. Interacts (via NID domains) with NMI (via NID domains); the interaction is direct and is facilitated by TRIM21.|||Knockout mice show decreased inflammatory response when exposed to infection or injury, which can lead to lower inflammation-induced mortality.|||Nucleus|||Phosphorylated. Dephosphorylation correlates with the formation of a complex with NMI.|||Secreted|||The NID domain 1 is involved in the negative regulation of p65/RELA transcription and the negative regulation of NF-kappa-B pathway activation. http://togogenome.org/gene/10090:Tkt ^@ http://purl.uniprot.org/uniprot/P40142 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the transketolase family.|||Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+).|||Binds 1 thiamine pyrophosphate per subunit.|||Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.|||Homodimer. http://togogenome.org/gene/10090:Uspl1 ^@ http://purl.uniprot.org/uniprot/Q3ULM6 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Cajal body|||Interacts with ELL.|||Probably inactive as a hydrolase due to lack of catalytic Cys and His.|||SUMO-specific isopeptidase involved in protein desumoylation. Specifically binds SUMO proteins with a higher affinity for SUMO2 and SUMO3 which it cleaves more efficiently. Also able to process full-length SUMO proteins to their mature forms (By similarity). Plays a key role in RNA polymerase-II-mediated snRNA transcription in the Cajal bodies (By similarity). Is a component of complexes that can bind to U snRNA genes (By similarity). http://togogenome.org/gene/10090:Oprm1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Z2|||http://purl.uniprot.org/uniprot/P42866 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||During adult neurogenesis in hippocampus, increased numbers of granule cells maturing into neurons, larger granule cell layers and increased numbers of granule cells.|||Endosome|||Forms homooligomers and heterooligomers with other GPCRs, such as OPRD1, OPRK1, OPRL1, NPFFR2, ADRA2A, SSTR2, CNR1 and CCR5 (probably in dimeric forms) (PubMed:10842167, PubMed:12270145, PubMed:18836069, PubMed:21422164). Interacts with heterotrimeric G proteins; interaction with a heterotrimeric complex containing GNAI1, GNB1 and GNG2 stabilizes the active conformation of the receptor and increases its affinity for endomorphin-2, the synthetic opioid peptide DAMGO and for morphinan agonists (PubMed:26245379). Interacts with PPL; the interaction disrupts agonist-mediated G-protein activation. Interacts (via C-terminus) with DNAJB4 (via C-terminus). Interacts with calmodulin; the interaction inhibits the constitutive activity of OPRM1; it abolishes basal and attenuates agonist-stimulated G-protein coupling. Interacts with FLNA, PLD2, RANBP9 and WLS and GPM6A (By similarity). Interacts with RTP4 (PubMed:18836069). Interacts with SYP and GNAS (By similarity). Interacts with RGS9, RGS17, RGS20, RGS4, PPP1R9B and HINT1 (PubMed:15827571, PubMed:17725581, PubMed:18439408, PubMed:21153910). Isoform 9 interacts with GRPR (PubMed:22000021).|||Isoform 9 is involved in morphine-induced scratching and seems to cross-activate GRPR in response to morphine.|||Membrane|||Perikaryon|||Phosphorylated. Differentially phosphorylated in basal and agonist-induced conditions. Agonist-mediated phosphorylation modulates receptor internalization. Phosphorylated by GRK2 in a agonist-dependent manner. Phosphorylation at Tyr-166 requires receptor activation, is dependent on non-receptor protein tyrosine kinase Src and results in a decrease in agonist efficacy by reducing G-protein coupling efficiency. Phosphorylated on tyrosine residues; the phosphorylation is involved in agonist-induced G-protein-independent receptor down-regulation. Phosphorylation at Ser-375 is involved in G-protein-dependent but not beta-arrestin-dependent activation of the ERK pathway.|||Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:21422164, PubMed:22437502, PubMed:10842167, PubMed:16682964, PubMed:26245379, PubMed:7797593, PubMed:9037090). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:16682964, PubMed:7797593, PubMed:9037090). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (PubMed:6933569, PubMed:35201898). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:10842167, PubMed:21422164, PubMed:22437502). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:9767386, PubMed:26245379). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (PubMed:15827571, PubMed:17725581). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (PubMed:12642578). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity).|||Ubiquitinated. A basal ubiquitination seems not to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.|||axon|||dendrite http://togogenome.org/gene/10090:Cfh ^@ http://purl.uniprot.org/uniprot/E9Q8I0|||http://purl.uniprot.org/uniprot/P06909 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Polymorphism|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ CFH is one of the most abundant complement components in blood where the liver is the major source of CFH protein in vivo. in addition, CFH is secreted by additional cell types including monocytes, fibroblasts, or endothelial cells.|||Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces. Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of the complement amplification loop. As a cofactor of the serine protease factor I, CFH also regulates proteolytic degradation of already-deposited C3b. In addition, mediates several cellular responses through interaction with specific receptors. For example, interacts with CR3/ITGAM receptor and thereby mediates the adhesion of human neutrophils to different pathogens. In turn, these pathogens are phagocytosed and destroyed.|||Homodimer. Forms also homooligomers. Interacts with complement protein C3b; this interaction inhibits complement activation. Interacts with complement protein C3d. Interacts with CR3/ITGAM; this interaction mediates adhesion of neutrophils to pathogens leading to pathogen clearance.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||Sulfated on tyrosine residues.|||Sushi 1-3 domain represents the minimal unit capable of cofactor activity. The property to discriminate self surfaces from non-self surfaces depends on the C-terminal region made of Sushis 19-20.|||The lack of CFH alters the microarchitecture of bone and affects osteoblast and osteoclast dynamics.|||Two codominant alleles of factor H are present in mice. http://togogenome.org/gene/10090:Defa27 ^@ http://purl.uniprot.org/uniprot/F2Z403 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Lss ^@ http://purl.uniprot.org/uniprot/Q8BLN5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the terpene cyclase/mutase family.|||Endoplasmic reticulum membrane|||Key enzyme in the cholesterol biosynthesis pathway. Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus. Through the production of lanosterol may regulate lens protein aggregation and increase transparency.|||Monomer. http://togogenome.org/gene/10090:Nrp2 ^@ http://purl.uniprot.org/uniprot/O35375|||http://purl.uniprot.org/uniprot/Q3U5I8|||http://purl.uniprot.org/uniprot/Q8QZY7 ^@ Caution|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neuropilin family.|||Expressed in developing CNS, PNS and in some nonneural tissues including limb buds, developing bones, muscles, intestinal epithelium, kidney, lung and submandibular gland.|||Heterodimer with NRP1. Binds PLXNB1 (By similarity).|||High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||The expression pattern is very dynamic and is developmentally regulated.|||The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding. http://togogenome.org/gene/10090:Bola1 ^@ http://purl.uniprot.org/uniprot/Q9D8S9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins (By similarity). Probably acts together with the monothiol glutaredoxin GLRX5. May protect cells against oxidative stress (By similarity).|||Belongs to the BolA/IbaG family.|||Interacts with GLRX5.|||Mitochondrion http://togogenome.org/gene/10090:Stkld1 ^@ http://purl.uniprot.org/uniprot/Q80YS9 ^@ Caution|||Domain|||Similarity ^@ Asn-126 is present instead of the conserved Asp which is expected to be an active site residue.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily.|||The protein kinase domain is predicted to be catalytically inactive. http://togogenome.org/gene/10090:Cyb5d1 ^@ http://purl.uniprot.org/uniprot/Q5NCY3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome b5 family.|||Radial spoke stalk protein that binds heme under oxidizing conditions. Required for the coordinated beating of multiple cilia maybe by functioning in a redox signaling pathway.|||cilium axoneme http://togogenome.org/gene/10090:Nlgn1 ^@ http://purl.uniprot.org/uniprot/E9QK34|||http://purl.uniprot.org/uniprot/Q99K10 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type-B carboxylesterase/lipase family.|||Brain and arteries (at protein level). Expressed in olfactory bulb. Detected in brain.|||Cell membrane|||Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep (PubMed:23716671). The protein is involved in nervous system development.|||Expressed in a circadian manner in the brain with highest expression seen at Zeitgeber time (ZT) 6 hours.|||Interacts with neurexins NRXN1, NRXN2 and NRXN3 (By similarity). Interaction with neurexins is mediated by heparan sulfate glycan modification on neurexin (PubMed:30100184). Interacts (via its C-terminus) with DLG4/PSD-95 (via PDZ domain 3). Interacts with AIP1, GOPC and PDZRN3 (By similarity). Interacts with NLGN3.|||Membrane|||No obvious phenotype, but mice present subtle behavorial changes with some deficits in spatial learning and memory. In addition, mice have reduced brain volume. Mice lacking both NLGN1 and NLGN2, or NLGN1 and NLGN3, are viable, but have impaired breathing, drastically reduced reproduction rates and striking deficits in raising their offspring. Mice lacking NLGN1, NLGN2 and NLGN3 are born at the expected Mendelian rate, but die shortly after birth due to respiratory failure. They do not show a significant change in the number of synapses, but synapse function is strongly impaired. Mice exhibit social novelty and fear-conditioning deficits and also show reduced wakefulness duration and altered EEG during wakefulness and sleep.|||Postsynaptic density|||Synaptic cell membrane|||Synaptic cleft http://togogenome.org/gene/10090:Smad9 ^@ http://purl.uniprot.org/uniprot/Q3UVC6|||http://purl.uniprot.org/uniprot/Q9JIW5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dwarfin/SMAD family.|||Cytoplasm|||Interaction with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit (By similarity). Interacts with RANBP3L (By similarity).|||Nucleus|||Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase and activin type I receptor-like kinases (ALK-2, ALK-3 and ALK-6).|||Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD9 is a receptor-regulated SMAD (R-SMAD). Has been shown to be activated by activin type I receptor-like kinases (ALK-2, ALK-3, ALK-6) which stimulate heteromerization between SMAD9 and SMAD4. May play a role in osteoblast differentiation and maturation. http://togogenome.org/gene/10090:Bcl2l10 ^@ http://purl.uniprot.org/uniprot/Q9Z0F3 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Bcl-2 family.|||Endoplasmic reticulum|||Expressed during all phases of oocyte maturation; localized at the meiotic spindle and spindle poles during meiosis.|||Expressed in multiple embryonic tissues (PubMed:9829980). Restricted to the ovary and testis in adult mice (PubMed:9878060, PubMed:9829980).|||Interacts with BAX (By similarity). Interacts with BCL2 and BCL2L1/BCLX (By similarity). Interacts with APAF1 (PubMed:9878060, PubMed:9829980). Interacts with ITPR1, ITPR2 and ITPR3; the interaction with ITPR1 is increased in the presence of AHCLY1 (By similarity). Interacts with AHCYL1 (By similarity). Interacts with HIP1R (via ENTH and I/LWEQ domains) (By similarity). Interacts with CASP9 (By similarity). Interacts with BCL2L11/BIM (By similarity). Interacts with BIK (By similarity). Interacts with UBQLN4 (By similarity). Interacts with NME2/NM23-H2 (PubMed:17532299). Interacts with PMAIP1/NOXA (By similarity). Interacts with TPX2 (PubMed:27753540). Interacts with UBQLN1; in the cytoplasm (By similarity). Interacts (via BH1 domain) with BECN1 (By similarity).|||Mitochondrion|||Monoubiquitinated by UBQLN1; results in stabilization of BCL2L10 protein abundance and in relocalization from mitochondria to cytoplasm.|||Nucleus membrane|||Promotes cell survival by suppressing apoptosis induced by BAX but not BAK (By similarity). Increases binding of AHCYL1/IRBIT to ITPR1 (By similarity). Reduces ITPR1-mediated calcium release from the endoplasmic reticulum cooperatively with AHCYL1/IRBIT under normal cellular conditions (By similarity). Under apoptotic stress conditions, dissociates from ITPR1 and is displaced from mitochondria-associated endoplasmic reticulum membranes, leading to increased Ca(2+) transfer to mitochondria which promotes apoptosis (By similarity). Required for the correct formation of the microtubule organizing center during oocyte cell division, potentially via regulation of protein abundance and localization of other microtubule organizing center components such as AURKA and TPX2 (PubMed:27753540).|||spindle http://togogenome.org/gene/10090:Dennd1b ^@ http://purl.uniprot.org/uniprot/Q3U1T9 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in a subset of dendritic cells (DCs).|||Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells. Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Plays a role in clathrin-mediated endocytosis. Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity. Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells.|||Interacts with RAB35 (PubMed:26774822). Interacts with clathrin heavy chain/CLTC (By similarity). Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 (By similarity). Interacts with CD3E (PubMed:26774822).|||Mice are developmentally normal and fertile but accumulate more splenic and lymph node CD4(+) and CD8(+) effector/memory T-cells with age. TH2 cells display increased TCR-mediated responses, due to delayed surface TCR down-modulation and recycling, and increased production of cytokines. Mice have increased antigen-induced allergic responses.|||Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity.|||The FXDXF motif mediates interaction the AP-2 complex.|||The clathrin box motif mediates interaction with clathrin.|||clathrin-coated vesicle|||cytosol http://togogenome.org/gene/10090:Dixdc1 ^@ http://purl.uniprot.org/uniprot/Q80Y83 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in brain and testis and to a lower extent in lung, kidney, colon, ovary and urinary bladder. Expressed in brain, liver, testis and spleen (at protein level). Expressed throughout the brain with strong expression in main and accessory olfactory bulbs, cerebral cortex, piriform cortex, hippocampus, habenular nucleus, dorsal thalamus, superior and inferior colliculi and cerebellum.|||Belongs to the DIXDC1 family.|||Cytoplasm|||Expressed in embryonic brain, liver and spleen (at protein level). First detected at 7.5 dpc in the node. Expressed in the cephalic mesenchyme and tail bud at 8.5 dpc, and in the branchial arch and forelimb bud at 9.5 dpc. In the central nervous system, expression begins and persists in the regions where the neurons differentiate. Expression is also strong in the peripheral nervous system, including sensory cranial ganglia, dorsal root ganglia, and autonomic ganglia, and in the sensory organs, such as the inner nuclear layer of the neural retina, saccule and cochlea of the inner ear, and nasal epithelium. Outside the nervous system, expression is detected in the cartilage, tongue, lung bud, stomach, and gonad from 12.5 dpc to 14.5 dpc, and in the tooth bud, bronchial epithelium, and kidney at 17.5 dpc.|||Major isoform.|||May bind filamentous actin. Directly interacts (via DIX domain) with DVL2 (via DIX domain). Interacts with gamma-tubulin (By similarity). Interacts with the complex composed of DVL2 and Rac. Interacts with AXIN1; competes with MAP3K1. Interacts with MAP3K4 preventing MAP3K4 interaction with AXIN1.|||Phosphorylated on tyrosine and serine residues.|||Polyubiquitinated, leading to its proteasomal degradation. WNT3A signaling increases DIXDC1 protein levels by inhibiting its ubiquitination and subsequent degradation.|||Positive effector of the Wnt signaling pathway; activates WNT3A signaling via DVL2. Regulates JNK activation by AXIN1 and DVL2.|||The DIX domain mediates interaction with AXIN1 and inhibition of AXIN1-mediated JNK activation through MAP3K1. Mediates interaction with DVL2; this interaction is required for activation of Wnt signaling (By similarity).|||The coiled-coil domain mediates interaction with MAP3K4 and inhibition of AXIN1-mediated JNK activation through MAP3K4.|||focal adhesion|||stress fiber http://togogenome.org/gene/10090:Nme8 ^@ http://purl.uniprot.org/uniprot/Q715T0 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains 3 inactive NDK domains that each lack the active His residue, suggesting that they have no NDP kinase activity.|||Cytoplasm|||First expressed after puberty.|||In the C-terminal section; belongs to the NDK family.|||Monomer.|||Probably required during the final stages of sperm tail maturation in the testis and/or epididymis, where extensive disulfide bonding of fibrous sheath (FS) proteins occurs. May be involved in the reduction of disulfide bonds within the sperm FS components. In vitro, it has neither NDP kinase nor reducing activity on disulfide bonds (By similarity).|||Testis-specific. Expressed mainly in round spermatids. http://togogenome.org/gene/10090:Tcap ^@ http://purl.uniprot.org/uniprot/O70548 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with MYOZ1, MYOZ2 and MYOZ3. Interacts with CSRP3. Interacts directly with the N-terminal Ig-like domains of 2 titin (TTN) molecules. Interacts with ANKRD2; the interaction is direct (By similarity).|||Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk (By similarity).|||sarcomere http://togogenome.org/gene/10090:Prpf38a ^@ http://purl.uniprot.org/uniprot/B2RTE3|||http://purl.uniprot.org/uniprot/Q4FK66 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRP38 family.|||Component of the spliceosome B complex.|||Component of the spliceosome B complex. Interacts (via N-terminal interaction domain) with ZMAT2 and MFAP1.|||Involved in pre-mRNA splicing as a component of the spliceosome.|||Nucleus http://togogenome.org/gene/10090:Gfral ^@ http://purl.uniprot.org/uniprot/Q6SJE0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GDNFR family.|||Brainstem-restricted receptor for GDF15 which regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846099, PubMed:28846097, PubMed:28846098). Upon interaction with its ligand, GDF15, interacts with RET and induces cellular signaling through activation of MAPK- and AKT- signaling pathways (PubMed:28846098, PubMed:28846099).|||Cell membrane|||Expressed in the brainstem, restricted to cells in the area postrema and the immediately adjacent region of the nucleus tractus solitarius.|||Interacts (via the extracellular domain) with GDF15 and RET; receptor of GDF15, mediates cellular signaling through interaction with RET after GDF15-binding (PubMed:28846098, PubMed:28846099). Interaction with RET requires previous GDF15-binding (PubMed:28846099).|||On a chow diet, mutants show no difference in food intake, energy expenditure or body weight compare to wild-type controls. On high-fat diet, they gain substantially more weight and are more glucose intolerant. Diet-induced obese mutants are hyperphagic and have 32% greater total mass and 9% greater lean mass than diet-induced obese wild-type mice (PubMed:28953886, PubMed:28846097, PubMed:28846099). Upon chronical administration of GDF15, mutants are refractory to the GDF15 effects in comparison to wild-types that show attenuated food-intake and sustained weightloss (PubMed:28846098, PubMed:28953886, PubMed:28846097, PubMed:28846099). http://togogenome.org/gene/10090:Xpot ^@ http://purl.uniprot.org/uniprot/A0A1W2P7Q6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the exportin family.|||Cytoplasm|||Nucleus|||tRNA nucleus export receptor which facilitates tRNA translocation across the nuclear pore complex. http://togogenome.org/gene/10090:Pgf ^@ http://purl.uniprot.org/uniprot/P49764|||http://purl.uniprot.org/uniprot/Q544A5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Antiparallel homodimer; disulfide-linked. Also found as heterodimer with VEGFA/VEGF (By similarity).|||Belongs to the PDGF/VEGF growth factor family.|||Growth factor active in angiogenesis and endothelial cell growth, stimulating their proliferation and migration. It binds to the receptor FLT1/VEGFR-1. Also promotes cell tumor growth (By similarity).|||Secreted http://togogenome.org/gene/10090:Extl1 ^@ http://purl.uniprot.org/uniprot/Q3TSP4|||http://purl.uniprot.org/uniprot/Q9JKV7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 47 family.|||Endoplasmic reticulum membrane|||Glycosyltransferase required for the biosynthesis of heparan-sulfate (HS). Transfers N-acetyl-alpha-D-glucosamine to the nascent HS chain (GlcNAcT-II activity). Appears to lack GlcNAcT I and GlcAT-II activities.|||Membrane http://togogenome.org/gene/10090:Ccbe1 ^@ http://purl.uniprot.org/uniprot/Q3MI99 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CCBE1 family.|||Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis.|||Secreted http://togogenome.org/gene/10090:Tcp11x2 ^@ http://purl.uniprot.org/uniprot/A2AEI7|||http://purl.uniprot.org/uniprot/Q9DAK1 ^@ Similarity ^@ Belongs to the TCP11 family. http://togogenome.org/gene/10090:Crat ^@ http://purl.uniprot.org/uniprot/P47934 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the carnitine/choline acetyltransferase family.|||Catalyzes the reversible transfer of acyl groups from carnitine to coenzyme A (CoA) and regulates the acyl-CoA/CoA ratio. Also plays a crucial role in the transport of fatty acids for beta-oxidation. Responsible for the synthesis of short- and branched-chain acylcarnitines. Active towards some branched-chain amino acid oxidation pathway (BCAAO) intermediates. Trans-2-enoyl-CoAs and 2-methylacyl-CoAs are poor substrates.|||Endoplasmic reticulum|||Mitochondrion inner membrane|||Monomer.|||Peroxisome http://togogenome.org/gene/10090:Lep ^@ http://purl.uniprot.org/uniprot/P41160|||http://purl.uniprot.org/uniprot/Q544U0 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the leptin family.|||Defects in Lep are the cause of profound obesity and type II diabetes.|||Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways (PubMed:15899045, PubMed:16825198, PubMed:11373681, PubMed:12594516, PubMed:20620997). In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity (By similarity) (PubMed:8589726, PubMed:10660043, PubMed:25383904, PubMed:25060689, PubMed:9732873, PubMed:12594516). In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides (By similarity) (PubMed:20620997, PubMed:11373681). In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption. Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways (By similarity) (PubMed:16825198, PubMed:20620997). May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression (By similarity). Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) (PubMed:16825198). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells (Probable). Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38 (PubMed:15899045). In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses (By similarity). Increases CD4(+)CD25(-) T cells proliferation and reduces autophagy during TCR (T cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation (PubMed:25060689).|||Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity. In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides. In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption. Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways. May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression. Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells. Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38. In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses. Increases CD4(+)CD25(-) T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.|||Mutants are severely obese and sterile (PubMed:8589726). Animals have an increased bone formation leading to high bone mass (PubMed:10660043). Have impaired T-cell immunity, Th2 responses are favoured in mutants (PubMed:9732873). CD4(+)CD25(-) T-cells of mutant mice show high levels of autophagy (PubMed:25060689).|||Secreted http://togogenome.org/gene/10090:Hsd3b2 ^@ http://purl.uniprot.org/uniprot/P26149 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.|||Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Liver and kidney.|||Mitochondrion membrane http://togogenome.org/gene/10090:Actr6 ^@ http://purl.uniprot.org/uniprot/A0A0R4J009|||http://purl.uniprot.org/uniprot/Q9D864 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin family.|||Belongs to the actin family. ARP6 subfamily.|||Component of the chromatin-remodeling SRCAP complex composed of at least SRCAP, DMAP1, RUVBL1, RUVBL2, ACTL6A, YEATS4, ACTR6 and ZNHIT1. Interacts with CBX1, CBX3 and CBX5.|||Nucleus|||Required for formation and/or maintenance of proper nucleolar structure and function (By similarity). Plays a dual role in the regulation of ribosomal DNA (rDNA) transcription (By similarity). In the presence of high glucose, maintains active rDNA transcription through H2A.Z deposition and under glucose starvation, is required for the repression of rDNA transcription, and this function may be independent of H2A.Z (By similarity).|||cytoskeleton|||nucleolus http://togogenome.org/gene/10090:Rnf130 ^@ http://purl.uniprot.org/uniprot/Q8VEM1 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an E3 ubiquitin-protein ligase (By similarity). May have a role during the programmed cell death of hematopoietic cells.|||Cytoplasm|||Expression is highest in liver, with lesser amounts in the lung, spleen, brain, heart, kidney and testis.|||Membrane|||Up-regulated in response to interleukin-3 (IL-3) withdrawal-induced apoptosis of 32Dcl3 cells (derived from bone marrow). http://togogenome.org/gene/10090:Ccdc66 ^@ http://purl.uniprot.org/uniprot/Q6NS45 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the retina from postnatal stages to adulthood. Highest levels are observed at postnatal stage P1 and P4 and expression decreases afterward. Steady levels are observed from P12 to adulthood. Expression increases in the outer segments from P12 to P19 paralleling the differentiation of outer segments.|||Homodimer; disulfide-linked (Probable). Interacts with CEP290. Interacts with PCM1 (By similarity). Interacts with ARMC9, TOGARAM1, CSPP1 and CEP104 (By similarity).|||Mice lacking Ccdc66 are viable but display degeneration of the retina. Initial formation of the retina is normal up to postnatal stage P10. Malformation of photoreceptors develops around P13. The degeneration progresses slowly until 3 months after birth, when the outer nuclear layer is reduced to 5-6 rows. From 5 to 7 months, only a thin outer nuclear and photoreceptor layer with severely shrunken outer and inner segments is preserved. It is associated with impaired photoreceptor function with early visual impairment detectable 1 month after birth and progressing slightly until 7 months.|||Microtubule-binding protein required for ciliogenesis. May function in ciliogenesis by mediating the transport of proteins like BBS4 to the cilium, but also through the organization of the centriolar satellites (By similarity). Plays a role in retina morphogenesis and/or homeostasis (PubMed:21680557).|||Partial nucleotide duplication in position 392 that disrupts the frame.|||Photoreceptor inner segment|||Widely expressed (PubMed:19777273). Expressed in retina by rod photoreceptors but also detected in outer plexiform and ganglion cell layers (at protein level) (PubMed:21680557, PubMed:19777273).|||centriolar satellite|||centrosome|||cilium|||cilium basal body|||photoreceptor outer segment http://togogenome.org/gene/10090:Mllt11 ^@ http://purl.uniprot.org/uniprot/P97783|||http://purl.uniprot.org/uniprot/Q543U0 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MLLT11 family.|||Cofactor for the transcription factor TCF7. Involved in regulation of lymphoid development by driving multipotent hematopoietic progenitor cells towards a T-cell fate.|||Cytoplasm|||Detected in embryonic brain cortex.|||Interacts with HSPA8 and LAMP2 isoform A; the interaction may target MLLT11 for degradation via chaperone-mediated autophagy. Interacts with TCF7.|||Nucleus|||Ubiquitinated, leading to degradation.|||Up-regulated during neuronal differentiation (in vitro).|||centrosome http://togogenome.org/gene/10090:B3gat3 ^@ http://purl.uniprot.org/uniprot/P58158 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 43 family.|||Expressed in heart, aorta, bone, and also in osteoblasts.|||Glycosaminoglycans biosynthesis. Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal-beta-1,3-Gal-beta-1,4-Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. Can also play a role in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. Stimulates 2-phosphoxylose phosphatase activity of PXYLP1 in presence of uridine diphosphate-glucuronic acid (UDP-GlcUA) during completion of linkage region formation.|||Golgi apparatus membrane|||Homodimer; disulfide-linked. Interacts with PXYLP1; the interaction increases the 2-phosphoxylose phosphatase activity of PXYLP1 during completion of linkage region formation in a B3GAT3-mediated manner.|||N-glycosylated.|||cis-Golgi network http://togogenome.org/gene/10090:Pcdhga5 ^@ http://purl.uniprot.org/uniprot/Q91XY3 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Nova1 ^@ http://purl.uniprot.org/uniprot/Q9JKN6 ^@ Disease Annotation|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Defects in Nova1 leads to neuronal death in spinal and brainstem neurons.|||Expressed in neurons of the cortex, sub-cortex, cerebellum and brainstem (at protein level)(PubMed:10829067). Expressed in motor neurons, but not in glia (PubMed:10829067).|||Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion (PubMed:8558240, PubMed:15933722, PubMed:17065982, PubMed:14615540). It binds specifically to the sequences 5'-YCAY-3' and regulates splicing in only a subset of regulated exons (PubMed:9154818, PubMed:8558240, PubMed:14615540). Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhances spliceosome assembly and exon inclusion (PubMed:10719891). Binding to 5'-YCAY-3' clusters results in a local and asymmetric action to regulate spliceosome assembly and alternative splicing in neurons. Binding to an exonic 5'-YCAY-3' cluster changed the protein complexes assembled on pre-mRNA, blocking U1 snRNP (small nuclear ribonucleoprotein) binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhanced spliceosome assembly and exon inclusion (PubMed:17065982, PubMed:15933722). With NOVA1, they perform unique biological functions in different brain areas and cell types (PubMed:30638744). Autoregulates its own expression by acting as a splicing repressor (PubMed:15933722). Acts to activate the inclusion of exon E3A in the glycine receptor alpha-2 chain and of exon E9 in gamma-aminobutyric-acid receptor gamma-2 subunit via a distal downstream UCAU-rich intronic splicing enhancer (PubMed:12808107). Acts to regulate a novel glycine receptor alpha-2 chain splice variant (alpha-2N) in developing spinal cord (PubMed:17065982).|||Interacts with PTBP2; the interaction is direct.|||Nucleus|||The KH domain consists of approximately 70 amino acids and includes a conserved hydrophobic core, an invariant Gly-X-X-Gly motif, and an additional variable segment. The third KH domain (KH3) binds a hairpin RNA loop containing the 5'-UCAY-3' motif on targeted molecules. RNA binding by KH3 requires residues C-terminal to the KH domain. http://togogenome.org/gene/10090:Nrep ^@ http://purl.uniprot.org/uniprot/Q07475 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Down-regulated in lungs by dexamethasone treatment.|||Expressed in brain and fetal lung.|||Expressed mainly in neurons belonging to a late migration wave. During adulthood, it persists at a high level in the granular layer of the cerebellum, the hippocampus and the olfactory bulb. In lung, detected at low levels at the pseudoglandular stage (14.5 dpc), with expression starting to increase at the beginning of distal lung development (16.5 dpc) and remaining at the same level during saccular development (18.5 dpc). The expression levels are highest at the beginning of and during alveolar development (P5-P14) before decreasing again to low levels at the end of alveolization (P30).|||Interacts with FLNA (By similarity). Interacts with the latency-associated peptides (LAP) of TGFB1 and TGFB2; the interaction results in a decrease in TGFB autoinduction.|||May have roles in cellular differentiation. Ectopic expression induces differentiation of fibroblast into myofibroblast and myofibroblast ameboid migration. Increases retinoic-acid regulation of lipid-droplet biogenesis. May also have neural functions. Promotes axonal regeneration and augments motility of gliomas. Down-regulates the expression of TGFB1 and TGFB2 but not of TGFB3. May play a role in the regulation of alveolar generation.|||Normal heat and mechanical sensitivity, as well as normal formalin-induced inflammatory pain. Reduced formalin-induced avoidance behavior, which reflects pain-related negative emotion, indicating a role in the affective, but not in the sensory component of the pain. Also exhibits altered behavioral responses in learning and memory.|||Phosphorylated on Ser-59. Phosphorylation decreases stability and activity. http://togogenome.org/gene/10090:Nln ^@ http://purl.uniprot.org/uniprot/Q91YP2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M3 family.|||Binds 1 zinc ion per subunit.|||Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1.|||Mitochondrion intermembrane space|||cytosol http://togogenome.org/gene/10090:Rhox2g ^@ http://purl.uniprot.org/uniprot/L7MUB9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pax9 ^@ http://purl.uniprot.org/uniprot/P47242|||http://purl.uniprot.org/uniprot/Q3V1K1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Death shortly after birth. Mice lack thymus, parathyroid glands, ultimobranchial bodies and teeth. They show craniofacial and visceral malformations as well as malformations of their distal limbs.|||In the embryo, expressed in pharyngeal pouches and derivatives, developing vertebral column, tail, head and limbs.|||In the embryo, expression increases slightly from day 9.5 to day 11.5, remains almost constant until day 14.5 and then decreases.|||Interacts with KDM5B.|||Nucleus|||Transcription factor required for normal development of thymus, parathyroid glands, ultimobranchial bodies, teeth, skeletal elements of skull and larynx as well as distal limbs. http://togogenome.org/gene/10090:Ilkap ^@ http://purl.uniprot.org/uniprot/Q8R0F6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Cytoplasm|||Interacts with ILK.|||Protein phosphatase that may play a role in regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation. Selectively associates with integrin linked kinase (ILK), to modulate cell adhesion and growth factor signaling. Inhibits the ILK-GSK3B signaling axis and may play an important role in inhibiting oncogenic transformation (By similarity). http://togogenome.org/gene/10090:Ece1 ^@ http://purl.uniprot.org/uniprot/A0A183ZRM3|||http://purl.uniprot.org/uniprot/Q4PZA2 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M13 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Converts big endothelin-1 to endothelin-1.|||Homodimer; disulfide-linked (By similarity). Interacts with PPP1R16B (By similarity).|||Inhibited by phosphoramidon.|||Membrane http://togogenome.org/gene/10090:Podn ^@ http://purl.uniprot.org/uniprot/Q7TQ62 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class V subfamily.|||Binds to type I collagen.|||Detected at low levels in normal embryonic kidney from embryonic day 14 through birth. Expression increases dramatically within 24 hours following birth and maximal levels coincide with the completion of morphogenesis at 2 weeks of age.|||Kidney. Expressed in podocytes and likely vascular endothelial cells within the glomerulus.|||N-glycosylated.|||Negatively regulates cell proliferation and cell migration, especially in smooth muscle cells.|||extracellular matrix http://togogenome.org/gene/10090:Or7g27 ^@ http://purl.uniprot.org/uniprot/Q7TRG2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gcm1 ^@ http://purl.uniprot.org/uniprot/P70348 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Placenta specific.|||Polyubiquitinated in the presence of UBE2D2 and FBXW2 (in vitro).|||Transcription factor that is necessary for placental development (PubMed:8962155). Involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes. Binds to the trophoblast-specific element 2 (TSE2) of the aromatase gene enhancer. Binds to the SYDE1 promoter. Has a central role in mediating the differentiation of trophoblast cells along both the villous and extravillous pathways in placental development (By similarity). http://togogenome.org/gene/10090:Alx3 ^@ http://purl.uniprot.org/uniprot/O70137|||http://purl.uniprot.org/uniprot/Q3UQX2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||Expressed in embryos from 8 days of gestation onward.|||Nucleus|||Predominantly in neural crest-derived mesenchyme and in lateral plate mesoderm. Prominent expression in frontonasal head mesenchyme and in the first and second pharyngeal arches and some of their derivatives. High expression is also seen in the tail and in many derivatives of the lateral plate mesoderm including the limbs, the body wall, and the genital tubercle.|||Transcriptional regulator with a possible role in patterning of mesoderm during development. http://togogenome.org/gene/10090:Masp1 ^@ http://purl.uniprot.org/uniprot/A0A2R8VHR3|||http://purl.uniprot.org/uniprot/P98064 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoproteolytic processing of the proenzyme produces the active enzyme composed on the heavy and the light chain held together by a disulfide bond. Isoform 1 but not isoform 2 is activated through autoproteolytic processing (By similarity).|||Belongs to the peptidase S1 family.|||Contains a N-linked (GlcNAc...) asparagine at position 538 Contains a N-linked (GlcNAc...) asparagine at position 604.|||Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5. Also plays a role in development.|||Homodimer. Interacts with the oligomeric lectins MBL2, FCN2 and FCN3; triggers the lectin pathway of complement through activation of C3. Interacts with SERPING1. Interacts with COLEC11; probably triggers the lectin pathway of complement.|||Inhibited by SERPING1 and A2M.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mice are smaller and more vulnerable indicating developmental and growth defects. Mice serum has low C4 and C3 cleavage activity together with low MASP2 activation.|||N-glycosylated. Some N-linked glycan are of the complex-type (By similarity).|||Protein of the plasma which is primarily expressed by liver.|||Secreted|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Katnal1 ^@ http://purl.uniprot.org/uniprot/Q8K0T4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily. A-like 1 sub-subfamily.|||Cytoplasm|||Expressed in Sertoli cells from 15.5 dpc onwards (at protein level).|||Interacts with KATNB1 and KATNBL1.|||Regulates microtubule dynamics in Sertoli cells, a process that is essential for spermiogenesis and male fertility. Severs microtubules in an ATP-dependent manner, promoting rapid reorganization of cellular microtubule arrays (PubMed:22654668). Has microtubule-severing activity in vitro (By similarity).|||Widely expressed, including in testis, brain, heart, lung, kidney, liver, spleen, seminal vesicles and ovary. In testis, restricted to Sertoli cells within the seminiferous epithelium (at protein level).|||cytoskeleton|||spindle|||spindle pole http://togogenome.org/gene/10090:Letm1 ^@ http://purl.uniprot.org/uniprot/Q9Z2I0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LETM1 family.|||Contaminating sequence. Potential poly-A sequence.|||Homohexamer (PubMed:27669901). Interacts with BCS1L (By similarity). Interacts with GHITM (By similarity).|||Inhibited by ruthenium red or its derivative Ru360.|||Knockout Letm1 homozygous mice show embryonic lethality before day E6.5 and around 50% of the heterozygotes die before day E13.5 (PubMed:23716663). Surviving mice show reduced mitochondrial calcium uptake, impaired mitochondrial ATP generation capacity, disrupted early embryonic development, altered glucose metabolism and increased susceptibility to seizures (PubMed:23716663).|||Mitochondrion inner membrane|||PINK1-mediated phosphorylation at Thr-191, positively regulates its mitochondrial calcium transport activity.|||Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (PubMed:27669901, PubMed:23716663). Mediates proton-dependent calcium efflux from mitochondrion (PubMed:27669901, PubMed:23716663). Functions also as an electroneutral mitochondrial proton/potassium exchanger (By similarity). Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain (By similarity). Required for the maintenance of the tubular shape and cristae organization (By similarity). Essential for early embryonic development (PubMed:23716663). http://togogenome.org/gene/10090:Gngt2 ^@ http://purl.uniprot.org/uniprot/A2A614|||http://purl.uniprot.org/uniprot/Q61017|||http://purl.uniprot.org/uniprot/Q6P8Y9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||G proteins are composed of 3 units; alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.|||Membrane http://togogenome.org/gene/10090:Slc66a2 ^@ http://purl.uniprot.org/uniprot/Q80XM9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Bcdin3d ^@ http://purl.uniprot.org/uniprot/Q91YP1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily.|||Cytoplasm|||Interacts with DICER1; the interaction may be mediated by RNA.|||O-methyltransferase that specifically monomethylates 5'-monophosphate of cytoplasmic histidyl tRNA (tRNA(His)), acting as a capping enzyme by protecting tRNA(His) from cleavage by DICER1. Also able, with less efficiently, to methylate the 5' monophosphate of a subset of pre-miRNAs, acting as a negative regulator of miRNA processing. The 5' monophosphate of pre-miRNAs is recognized by DICER1 and is required for pre-miRNAs processing: methylation at this position reduces the processing of pre-miRNAs by DICER1. Was also reported to mediate dimethylation of pre-miR-145; however dimethylation cannot be reproduced by another group which observes a monomethylation of pre-miR-145. http://togogenome.org/gene/10090:Or4c11 ^@ http://purl.uniprot.org/uniprot/A2ATJ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mtap ^@ http://purl.uniprot.org/uniprot/Q9CQ65 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PNP/MTAP phosphorylase family. MTAP subfamily.|||Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates.|||Cytoplasm|||Homotrimer.|||Nucleus http://togogenome.org/gene/10090:Syne4 ^@ http://purl.uniprot.org/uniprot/H3BL35|||http://purl.uniprot.org/uniprot/Q8CII8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (By similarity). Behaves as a kinesin cargo, providing a functional binding site for kinesin-1 at the nuclear envelope. Hence may contribute to the establishment of secretory epithelial morphology, by promoting kinesin-dependent apical migration of the centrosome and Golgi apparatus and basal localization of the nucleus.|||Belongs to the nesprin family.|||Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies. Probably part of a SUN1-containing LINC complex. Interacts with kinesins KIF5B and KLC1.|||Expressed in secretory epithelial cells, such as those found in exocrine pancreas, bulbourethral gland, mammary gland and salivary gland (at protein level). Also expressed in the cochlea, where it is restricted primarily to the 3 rows of outer hair cells and 1 row of inner hair cells (at protein level). Not detected in other cells of the cochlea, including Deiter's cells and pillar cells, nor in liver and kidney (at protein level).|||In the cochlea, low expression at P0 and P15, then rises significantly by P30 and remains steady. In the HC11 cell line model, up-regulated during differentiation of mammary cells into milk-secreting cells (at protein level).|||Mice are born at the expected Mendelian rate and look overtly normal. In the cochlea, outer hair cells form, but appear to degenerate as hearing matures. Inner hair cells remain intact. Hearing loss is already detected at P15 and progresses at all frequencies by P60.|||Nucleus outer membrane|||The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.|||The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces. http://togogenome.org/gene/10090:Neurod1 ^@ http://purl.uniprot.org/uniprot/Q60867 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis.|||Cytoplasm|||Efficient DNA-binding requires dimerization with another bHLH protein (PubMed:12810726, PubMed:18069799). Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element (PubMed:18069799, PubMed:23395635). Interacts with EP300; the interaction is inhibited by NR0B2 (PubMed:9512516). Interacts with RREB1 (By similarity). Interacts with ATOH8 (PubMed:18560595).|||Expressed in glucagon- and ghrelin-producing cells of the pancreas at 14.5 dpc. Expressed in each of the hormone-producing cells population of the pancreas, except somatostatin-producing cells at 16.5 dpc (at protein level). Expressed during embryonic development. Expressed in the earliest islet precursor cells of the pancreas at 9.5 dpc. Expressed in neuronal cells in the inner ear between 9.5 and 12.5 dpc. Expressed within the otic epithelium and among the delaminating cells migrating away from the ear to form sensory neurons at 10.5 dpc. Expressed in the upper blade of the nascent dentate gyrus at 16.5 dpc.|||Expressed in pancreatic beta cells, pulmonary neuroendocrine cells and retinal interneurons amacrine cells (at protein level). Expressed in endocrine cells of the pancreas. Expressed in the inner layer of cerebellar external granular layer (EGL). Expressed in the Ammon's horn (AH), which includes the CA1-CA3 pyramidal layer and in granule cells of the dentate gyrus (DG). Expressed in photoreceptors of the outer nuclear layer (ONL), in a subset of cells in the lower half of the inner nuclear layer (INL), and in a subset of cells in the ganglion cell layer (GCL) of the retina. Expressed in cholinergic and AII amacrine cell types. Expressed in differentiating neurons of both the central and peripheral nervous systems.|||In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-336; which promotes dendritic growth (By similarity). Phosphorylated by MAPK1; phosphorylation regulates heterodimerization and DNA-binding activities. Phosphorylation on Ser-266 and Ser-274 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells.|||Mice are deaf and die shortly after birth due to neonatal diabetes that results from developmental and functional defects of the pancreatic endocrine cells. Show a loss of enteroendocrine cells in the small intestine, airway and alveolar epithelial cells in the lung, granular neuronal cells in the cerebellum, hippocampal dentate gyrus and sensory neurons in the inner ear due to extensive cell death that occurs during the early stages of differentiation.|||Nucleus|||Up-regulated by NKX2-2 and NEUROG3. http://togogenome.org/gene/10090:Spink4 ^@ http://purl.uniprot.org/uniprot/O35679 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the intestinal tract.|||Secreted http://togogenome.org/gene/10090:AB124611 ^@ http://purl.uniprot.org/uniprot/Q75VT8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Lpcat2 ^@ http://purl.uniprot.org/uniprot/Q8BYI6 ^@ Activity Regulation|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acetyltransferase activity is increased following acute inflammatory stimulation by lipopolysaccharide (LPS). Acyltransferase activity is unchanged.|||Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||By inflammatory stimulation by LPS and by ODN1826, a TLR9 ligand, but not by poly(I:C), a TLR3 ligand.|||Cell membrane|||Endoplasmic reticulum membrane|||Exhibits both acyltransferase and acetyltransferase activities (PubMed:17182612, PubMed:18156367, PubMed:18285344). Activity is calcium-dependent (PubMed:17182612). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:17182612, PubMed:18156367). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (PubMed:17182612, PubMed:18285344). Also converts lyso-PAF to 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (PC), a major component of cell membranes and a PAF precursor (PubMed:17182612). Under resting conditions, acyltransferase activity is preferred (PubMed:17182612). Upon acute inflammatory stimulus, acetyltransferase activity is enhanced and PAF synthesis increases (PubMed:17182612). Involved in the regulation of lipid droplet number and size (By similarity).|||Golgi apparatus membrane|||Highest expression is found in resident macrophages and casein-induced neutrophils followed by skin, colon, spleen and thioglycollate-induced macrophages. Detected in erythroleukemic cells but not in reticulocytes.|||Lipid droplet|||The HXXXXD motif is essential for acyltransferase activity. http://togogenome.org/gene/10090:Mapk13 ^@ http://purl.uniprot.org/uniprot/Q3UIB2|||http://purl.uniprot.org/uniprot/Q9Z1B7 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subunit ^@ Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1 (By similarity).|||Interacts with MAPK8IP2.|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. http://togogenome.org/gene/10090:Gpc2 ^@ http://purl.uniprot.org/uniprot/Q8BKV1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glypican family.|||Cell membrane|||Cell surface proteoglycan that bears heparan sulfate. May fulfill a function related to the motile behaviors of developing neurons (By similarity).|||Interacts (via heparan sulfate) with PTN; this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2. Interacts (heparan sulfate chain) with MDK; this interaction is inhibited by heparin followed by chondroitin sulfate E; this interaction induces GPC2 clustering through heparan sulfate chain; this interaction induces neuronal cell adhesion and neurite outgrowth (By similarity).|||extracellular space http://togogenome.org/gene/10090:Ciao1 ^@ http://purl.uniprot.org/uniprot/Q99KN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat CIA1 family.|||Component of the CIA complex. Interacts with CIAO2A and forms a complex with CIAO2B and MMS19; the interactions with CIAO2A and CIAO2B are mutually exclusive (PubMed:23891004) (By similarity). Interacts with CHD1L, ERCC2, IREB2 and POLD1 (By similarity). Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with WT1 (By similarity). Interacts with CIAO3 (By similarity). Interacts (via LYR motif) with HSC20.|||Cytoplasm|||Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins (By similarity). As a CIA complex component, interacts specifically with CIAO2A or CIAO2B and MMS19 to assist different branches of iron-sulfur protein assembly, depending of its interactors. The complex CIAO1:CIAO2B:MMS19 binds to and facilitates the assembly of most cytosolic-nuclear Fe/S proteins. CIAO1:CIAO2A specifically matures ACO1 and stabilizes IREB2 (By similarity). Seems to specifically modulate the transactivation activity of WT1. As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation (By similarity). http://togogenome.org/gene/10090:Uqcc6 ^@ http://purl.uniprot.org/uniprot/Q8BTC1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UQCC6 family.|||Highly expressed in brown adipose, cardiac and skeletal muscle (at protein level).|||Interacts with UQCRC1 (PubMed:32161263). Interacts with UQCRQ (PubMed:32161263). Interacts with UQCC5 (By similarity). Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion (PubMed:35977508). Forms a complex, named COMA, composed of UQCC1, UQCC2 and UQCC4; activates MT-CYB translation (PubMed:35977508). Forms a complex, named COMC, composed of UQCC1, UQCC2; UQCC3 and UQCC4; mediates MT-CYB hemylation and association with the first nuclear-encoded complex III subunit UQCRQ (PubMed:35977508). Interacts with MT-CYB (PubMed:35977508).|||Mitochondrion inner membrane|||Required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative phosphorylation (PubMed:32161263, PubMed:35977508). Mediates early complex III biogenesis (PubMed:35977508). Participates in regulating the levels of electron transport chain proteins, and therefore energy supply, in response to changes in energy demand (PubMed:35977508). Also required for cytochrome c oxidase complex (complex IV) assembly (By similarity).|||Uqcc6 deficiency leads to complete loss of mitochondrial respiratory chain complex III, resulting in growth retardation and a mild increase in blood lactate levels and significantly decreased exercise tolerance. The subunits of mitochondrial respiratory chain complex I, II, IV, and V are not affected. http://togogenome.org/gene/10090:Frmd3 ^@ http://purl.uniprot.org/uniprot/Q8BHD4 ^@ Function|||Subcellular Location Annotation ^@ Membrane|||Putative tumor suppressor gene that may be implicated in the origin and progression of lung cancer. http://togogenome.org/gene/10090:Ugt2b1 ^@ http://purl.uniprot.org/uniprot/Q8R084 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Calb1 ^@ http://purl.uniprot.org/uniprot/P12658 ^@ Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the calbindin family.|||Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase.|||Expressed in the modiolar nerve root and in bushy neurons in the ventral cochlear nucleus (at protein level).|||Interacts with RANBP9.|||This protein has four functional calcium-binding sites; potential sites II and VI have lost affinity for calcium. http://togogenome.org/gene/10090:Mnd1 ^@ http://purl.uniprot.org/uniprot/Q8K396 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MND1 family.|||Heterodimer with PSMC3IP/HOP2. MND1-PSMC3IP interacts with DMC1 and RAD51 and binds to ssDNA and dsDNA showing no preference for either form of DNA.|||Nucleus|||Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis. Stimulates both DMC1- and RAD51-mediated homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks. http://togogenome.org/gene/10090:Cyp2u1 ^@ http://purl.uniprot.org/uniprot/Q9CX98 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in the metabolism of arachidonic acid and its conjugates. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Acts as an omega and omega-1 hydroxylase for arachidonic acid and possibly for other long chain fatty acids. May modulate the arachidonic acid signaling pathway and play a role in other fatty acid signaling processes. May down-regulate the biological activities of N-arachidonoyl-serotonin, an endocannabinoid that has anti-nociceptive effects through inhibition of fatty acid amide hydrolase FAAH, TRPV1 receptor and T-type calcium channels. Catalyzes C-2 oxidation of the indole ring of N-arachidonoyl-serotonin forming a less active product 2-oxo-N-arachidonoyl-serotonin.|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed at all stages after 7 dpc. Expressed in brain structures including cortex, diencephalon, medulla oblongata, spine and cerebellum at 12 dpc. Expression in embryonic nervous system increases during development, as measured at 15 dpc and 18 dpc timepoints.|||Microsome membrane|||Mitochondrion inner membrane|||Widely expressed. Expressed in heart, brain and liver. http://togogenome.org/gene/10090:Myl12b ^@ http://purl.uniprot.org/uniprot/Q3THE2 ^@ Function|||Miscellaneous|||PTM|||Subunit ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains: interacts with myosin heavy chain MYO19.|||Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Phosphorylation triggers actin polymerization in vascular smooth muscle. Implicated in cytokinesis, receptor capping, and cell locomotion.|||Phosphorylation increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. It is required to generate the driving force in the migration of the cells but not necessary for localization of myosin-2 at the leading edge. Phosphorylation is reduced following epigallocatechin-3-O-gallate treatment.|||This chain binds calcium. http://togogenome.org/gene/10090:Gucy2e ^@ http://purl.uniprot.org/uniprot/P52785 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by GUCA1A when free calcium ions concentration is low, and inhibited by GUCA1A when free calcium ions concentration is high (PubMed:21598940). Negatively regulated by RD3; RD3 inhibits the basal and GUCA1A-stimulated guanylate cyclase activity (By similarity).|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Catalyzes the synthesis of cyclic GMP (cGMP) in rods and cones of photoreceptors. Plays an essential role in phototransduction, by mediating cGMP replenishment (PubMed:21598940). May also participate in the trafficking of membrane-asociated proteins to the photoreceptor outer segment membrane (PubMed:17255100).|||Deficient mice exhibit abnormal retinal cone cell morphology, impaired cone and rod electrophysiology, and severe retinal cone cell degeneration. GUCY2E and GUCY2F double knockout mice does not show any photoresponse, their rods and cones degenerate and the intracellular transport of some phototransduction proteins is impaired.|||Endoplasmic reticulum membrane|||Homodimer; requires homodimerization for guanylyl cyclase activity (By similarity). Interacts (via C-terminus) with RD3 (via C-terminus); promotes the exit of GUCY2E from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments (By similarity). Interaction with RD3 negatively regulates GUCY2E guanylate cyclase activity (By similarity).|||Photoreceptor outer segment membrane|||The gene name nomenclature of retinal guanylyl cyclase 1 is confusing; for mouse the gene name is GUCY2E whereas the gene name is GUCY2D for human and rat orthologs.|||There are 9 conserved cysteine residues in sensory guanylate cyclases, 6 in the extracellular domain, which may be involved in intra- or interchain disulfide bonds. http://togogenome.org/gene/10090:Chst1 ^@ http://purl.uniprot.org/uniprot/Q3UY35|||http://purl.uniprot.org/uniprot/Q9EQC0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.|||Broadly expressed with highest levels in central nervous system. Expressed in cortex (at protein level) (PubMed:24152993, PubMed:23254996). Expressed in high endothelial venules in peripheral lymph nodes, mesenteric lymph nodes and Peyer's patches (PubMed:23254996).|||Expressed in cortex and cerebellum throughout the postnatal period (at protein level).|||Golgi apparatus membrane|||Membrane|||Mutant mice are born at the expected Mendelian rate and have normal developmental and reproductive potential.|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of internal galactose (Gal) residues of keratan. Cooperates with B4GALT4 and B3GNT7 glycosyltransferases and CHST6 sulfotransferase to construct and elongate disulfated disaccharide unit [->3(6-sulfoGalbeta)1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Has a preference for sulfating keratan sulfate, but it also transfers sulfate to the unsulfated polymer (By similarity). Involved in biosynthesis of phosphacan, a major keratan sulfate proteoglycan in the developing brain (PubMed:24152993). Involved in biosynthesis of 6-sulfoGalbeta-containing O-linked glycans in high endothelial venules of lymph nodes. May act in a synergistic manner with CHST4 to generate sialyl 6',6-disulfo Lewis X motif, a recognition determinant for immune cell receptors implicated in leukocyte trafficking (PubMed:23254996) (By similarity). Catalyzes sulfation of N-acetyllactosamine (LacNAc) oligosaccharides with highest efficiency for sialylated LacNAc structures (By similarity). http://togogenome.org/gene/10090:Ndufaf2 ^@ http://purl.uniprot.org/uniprot/Q59J78 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a molecular chaperone for mitochondrial complex I assembly. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFA12 subunit family.|||Mitochondrion http://togogenome.org/gene/10090:Hspd1 ^@ http://purl.uniprot.org/uniprot/P63038 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ . Potential poly-A sequence.|||Belongs to the chaperonin (HSP60) family.|||Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein.|||Homoheptamer arranged in a ring structure. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. Interacts with 2 heptameric Hsp10 rings to form the symmetrical football complex (By similarity). Interacts with HRAS (PubMed:1347942). Interacts with ATAD3A. Interacts with ETFBKMT and EEF1AKMT3 (By similarity). Interacts with MFHAS1 (By similarity).|||Mitochondrion matrix http://togogenome.org/gene/10090:Nr4a3 ^@ http://purl.uniprot.org/uniprot/A0A6F8X1J9|||http://purl.uniprot.org/uniprot/Q9QZB6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR4 subfamily.|||Induced by inflammatory stimuli (PubMed:20558821). Up-regulated by the anorexigenic signal leptin via the transcription factor cyclic AMP response element-binding protein (CREB). Suppressed by orexigenic signal glucocorticoid that mobilizes NR3C1 to inhibit NR4A3 expression by antagonizing the action of CREB (PubMed:23897430).|||Interacts with SIX3 (via homeobox); differentially regulates the transcriptional activities of NR4A3. Interacts with NCOA2; potentiates the activity of the NR4A3 (PubMed:12709428). Interacts with NCOA1, NCOA3, MED1 and KAT2B. Interacts with EP300 and NCOA2; mediates the recruitment of MED1 in the coactivator complex (PubMed:12709428). Interacts with the constituents of DNA-PK heterotrimer PRKDC, XRCC6 and XRCC5; phosphorylates and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with NR3C1 (via nuclear receptor DNA-binding domain); the interactions represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE). Interacts with TRIM28; the interactions potentiates NR4A3 activity on NurRE promoter. Binds DNA as a monomer and homodimer. Interacts with PARP1; activates PARP1 by improving acetylation of PARP1 and suppressing the interaction between PARP1 and SIRT1 (By similarity).|||Not expressed during the earliest stages of vesicle formation (10.5 dpc). Expression begins coincidentally with the initiation of regional shape changes in the otic vesicle at 11.5 dpc and is restricted to the dorsolateral region. At 13.5 dpc, expression is limited to the inner edge of the semicircular canal epithelium, flanking the site of fusion, and this restricted expression continues at P1 (PubMed:11784868). At 14.5 dpc expression is observed in the primitive plexiform layer of the hippocampus. At P0, expression is observed in both the pyramidal and granule cell layers. Expression persistes in these cells in the adult hippocampus after their postnatal maturation. In addition, expression is also observed in the hilar mossy cells of the dentate gyrus (PubMed:15456880). At 7.5 dpc expression is ubiquitous, whereas at 9 dpc and 9.5 dpc, expression is restricted to the brain (PubMed:13129926).|||Nr4a3 homozygous knockout mice are viable and normal in appearance; however, abnormal hyperactive and partial bidirectional circling behavior is observed by 3 weeks of age in 15% of these mice. The circling behavior is interspersed with noncircling periods of feeding, grooming, and sleep (PubMed:11784868). A small percentage of adult Nr4a3 homozygotes displayes brief freezing spells with tonic posturing that are exacerbated with handling (PubMed:15456880). The overall food consumption of Nr4a3 homozygous knockout mice is higher. Moreover, Nr4a3 homozygous mice lose more body weight upon fasting but clearly consumed more food during refeeding. By the end of the fasting period, Nr4a3 homozygous mice display signs of exhaustion (PubMed:23897430). Nr4a3 homozygous leads to embryonic lethality around 8.5 dpc (PubMed:13129926).|||Nucleus|||Phosphorylated by PRKDC.|||The AF-1 domain mediates transcription activation. The N-terminal region (1-292) directly interacts with the C-terminal LBD (380-627): the interaction is potentiated by AF-1-mediated recruitment of NCOA2.|||Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner (PubMed:12709428). Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (PubMed:21868379). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner (PubMed:24806827). During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (PubMed:11784868). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance (PubMed:20566846, PubMed:15456880). Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (PubMed:19153266). Also plays a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (PubMed:24586680). Also plays a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1 (PubMed:23897430, PubMed:19523439). Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (PubMed:18325999). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (By similarity). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration (PubMed:13129926). Inhibits adipogenesis (PubMed:18945812). Also participates in cardiac hypertrophy by activating PARP1 (By similarity).|||Ubiquitous. Highest levels of expression in brain. Widely expressed throughout the arcuate nucleus region of the hypothalamus, namely in AgRP neurons. http://togogenome.org/gene/10090:Ccn5 ^@ http://purl.uniprot.org/uniprot/A2AHD1|||http://purl.uniprot.org/uniprot/Q9Z0G4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CCN family.|||May play an important role in modulating bone turnover. Promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, inhibits osteocalcin production (By similarity).|||Secreted http://togogenome.org/gene/10090:Slc39a5 ^@ http://purl.uniprot.org/uniprot/Q9D856 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the ZIP transporter (TC 2.A.5) family.|||Expressed at 10 dpc, postnatal day P0, P13 and adult.|||Expressed in all stages of eye development and primarily in the sclera and several layers of the retina, including the inner segment, outer plexiform layer and ganglion cell layer (PubMed:24891338). Expressed in pancreas, kidney and the proximal and distal small intestine as well as in the embryonic visceral yolk sac (PubMed:15358787). In the proximal intestine, expression is predominant in the crypts but diminishes toward the apical regions of the villi (PubMed:15358787).|||Homodimer.|||Homozygous knockout mice lacking Slc39a5 display normal fecondity and seem normal.|||Induced in a zinc-responsive manner (PubMed:18020946). During zinc deficiency, the transcript remains associated with polysomes and is rapidly resynthesized and targeted to the basolateral membranes of these cell types after zinc-repletion (PubMed:18020946).|||Methylated at His-371 by METTL9.|||N-Glycosylated.|||Uniporter that transports zinc(2+) into polarized cells of enterocytes, pancreatic acinar and endoderm cells across the basolateral membrane and participates, notably, in zinc excretion from the intestine by the uptake of zinc from the blood into the intestine (PubMed:15322118, PubMed:24303081). The transport mechanism is temperature- and concentration-dependent and saturable (PubMed:15322118). In addition, is also a high affinity copper transporter in vitro (By similarity). Also may regulate glucose-stimulated insulin secretion (GSIS) in islets primarily through the zinc-activated SIRT1-PPARGC1A axis (PubMed:30324491). Could regulate the BMP/TGF-beta (bone morphogenetic protein/transforming growth factor-beta) signaling pathway and modulates extracellular matrix (ECM) proteins of the sclera (By similarity). Plays a role in eye development (By similarity). http://togogenome.org/gene/10090:Or12d12 ^@ http://purl.uniprot.org/uniprot/Q920Z0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Col10a1 ^@ http://purl.uniprot.org/uniprot/Q05306 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homotrimer.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.|||extracellular matrix http://togogenome.org/gene/10090:Dhx29 ^@ http://purl.uniprot.org/uniprot/Q6PGC1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-binding RNA helicase involved in translation initiation. Part of the 43S pre-initiation complex that is required for efficient initiation on mRNAs of higher eukaryotes with structured 5'-UTRs by promoting efficient NTPase-dependent 48S complex formation. Specifically binds to the 40S ribosome near the mRNA entrance. Does not possess a processive helicase activity.|||Belongs to the DEAD box helicase family. DEAH subfamily.|||Cytoplasm|||Part of the 43S pre-initiation complex (PIC) that contains at least Met-tRNA, EIF1, EIF1A (EIF1AX or EIF1AY), EIF2S1, EIF2S2, EIF2S3, EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L, EIF3M, DHX29 and the 40S ribosomal subunit. http://togogenome.org/gene/10090:Myl9 ^@ http://purl.uniprot.org/uniprot/Q9CQ19 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Myosin is a hexamer of 2 heavy chains and 4 light chains: interacts with myosin heavy chain MYO19.|||Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Implicated in cytokinesis, receptor capping, and cell locomotion (By similarity). In myoblasts, regulates PIEZO1-dependent cortical actomyosin assembly involved in myotube formation (PubMed:29799007).|||Phosphorylation increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. It is required to generate the driving force in the migration of the cells but not necessary for localization of myosin-2 at the leading edge (By similarity). Phosphorylation is required for myotube formation (PubMed:29799007).|||This chain binds calcium.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Actl9 ^@ http://purl.uniprot.org/uniprot/Q8CG27 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin family.|||Interacts with ACTL7A.|||Testis-specic protein that plays an important role in fusion of proacrosomal vesicles and perinuclear theca formation.|||acrosome|||perinuclear theca http://togogenome.org/gene/10090:Vmn2r40 ^@ http://purl.uniprot.org/uniprot/F6W043 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nkx6-2 ^@ http://purl.uniprot.org/uniprot/D3Z4R4 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pcdhb14 ^@ http://purl.uniprot.org/uniprot/Q6PB90 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:L1cam ^@ http://purl.uniprot.org/uniprot/A2AFG8|||http://purl.uniprot.org/uniprot/Q6PGJ3 ^@ Similarity ^@ Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family. http://togogenome.org/gene/10090:Or5b113 ^@ http://purl.uniprot.org/uniprot/Q8VFW1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Brsk2 ^@ http://purl.uniprot.org/uniprot/Q69Z98 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-175 by STK11/LKB1.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Detected in pancreas islets and in brain (at protein level). Detected in brain and pancreas.|||Endoplasmic reticulum|||Interacts with FZR1, a regulatory subunit of the APC ubiquitin ligase complex. Interacts with COPS5. Interacts with PAK1 (By similarity).|||May be phosphorylated at Thr-261 by PKA (By similarity). Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-175 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-175 by PP2C.|||No visible phenotype. Mice are fertile and healthy. In contrast, mice lacking both Brsk1 and Brsk2 show little spontaneous movement and are only weakly responsive to tactile stimulation: they die within 2 hours of birth. Defects are due to impaired neuronal differentiation and polarity.|||Polyubiquitinated by the APC complex in conjunction with FZR1, leading to its proteasomal degradation. Targeted for proteasomal degradation by interaction with COPS5. BRSK2 levels change during the cell cycle. BRSK2 levels are low at the G1/S boundary and gradually increase as cells progress into G2 phase. BRSK2 levels decrease rapidly at the end of mitosis (By similarity).|||Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-504' and 'Ser-554'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-175 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-261 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress.|||The KEN box motif is required for interaction with FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination.|||centrosome|||perinuclear region http://togogenome.org/gene/10090:Tmprss11b ^@ http://purl.uniprot.org/uniprot/Q14C59 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Expressed in esophagus, cervix, tongue, and testes.|||Inhibited by aprotinin, leupeptin, benzamidine, SERPINA1, SPINT1 and SPINT2.|||Serine protease. http://togogenome.org/gene/10090:Xirp2 ^@ http://purl.uniprot.org/uniprot/Q4U4S6 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Xin family.|||By MEF2A in skeletal muscle. By angiotensin II in heart.|||Cell junction|||Expression is restricted to heart and skeletal muscle. Present in intercalated disks of the heart and in the Z-disk region of skeletal muscle (at protein level).|||Interacts with ACTN2. Interacts with F-actin (By similarity).|||Protects actin filaments from depolymerization.|||Xin repeats bind F-actin. http://togogenome.org/gene/10090:Col9a1 ^@ http://purl.uniprot.org/uniprot/Q05722 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.|||Covalently linked to the telopeptides of type II collagen by lysine-derived cross-links.|||Each subunit is composed of three triple-helical domains interspersed with non-collagenous domains. The globular domain at the N-terminus of type IX collagen molecules represents the NC4 domain which may participate in electrostatic interactions with polyanionic glycosaminoglycans in cartilage.|||Heterotrimer of an alpha 1(IX), an alpha 2(IX) and an alpha 3(IX) chain.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Structural component of hyaline cartilage and vitreous of the eye.|||extracellular matrix http://togogenome.org/gene/10090:Gzmd ^@ http://purl.uniprot.org/uniprot/P11033 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytolytic granule|||This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. http://togogenome.org/gene/10090:Rnf31 ^@ http://purl.uniprot.org/uniprot/Q924T7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated (PubMed:29950720). Interaction with OTULIN is required to suppress formation of 'Met-1'-linked polyubiquitin chains and prevent subsequent inactivation of the LUBAC complex (PubMed:29950720).|||Belongs to the RBR family.|||Cleaved by caspase during apoptosis.|||Component of the LUBAC complex (linear ubiquitin chain assembly complex) which consists of SHARPIN, RBCK1 and RNF31 (By similarity). LUBAC has a MW of approximately 600 kDa suggesting a heteromultimeric assembly of its subunits (By similarity). Associates with the TNF-R1 signaling complex (TNF-RSC) in a stimulation-dependent manner (By similarity). Interacts (via the PUB domain) with OTULIN (via the PIM motif); the interaction is direct (PubMed:23708998). Interacts (via the PUB domain) with VCP (via the PIM motif) (By similarity). Interacts (via the PUB domain) with SPATA2 (via the PIM motif); interaction is direct and bridges RNF31 and CYLD (By similarity). Interacts with CYLD; the interaction is indirect and is mediated via SPATA2 (By similarity). Interacts with MUSK (PubMed:14678832). Interacts with CARD11, promoting linear ubiquitination of BCL10 (By similarity).|||Cytoplasm|||E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:28701375). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (By similarity). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:28701375). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (By similarity). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (By similarity). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (By similarity). Recruited to the surface of bacteria by RNF213, which initiates the bacterial ubiquitin coat (By similarity). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (By similarity). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (By similarity). RNF31 is required for linear ubiquitination of BCL10, thereby promoting TCR-induced NF-kappa-B activation (By similarity). Binds polyubiquitin of different linkage types (By similarity).|||RING 1 and IBR zinc-fingers catalyze the first step transfer of ubiquitin from the E2 onto RING 2, to transiently form a HECT-like covalent thioester intermediate.|||The PUB domain mediates interaction with the PIM motifs of VCP and RNF31, with a strong preference for RNF31.|||The RanBP2-type zinc fingers mediate the specific interaction with ubiquitin.|||The UBA domain mediates association with RBCK1/HOIL1 via interaction with its UBL domain.|||The linear ubiquitin chain determining domain (LDD) mediates the final transfer of ubiquitin from RING 2 onto the N-terminus of a target ubiquitin.|||Widely expressed (at protein level). Not expressed in heart. http://togogenome.org/gene/10090:Dpep1 ^@ http://purl.uniprot.org/uniprot/P31428 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.|||Deficient mice are phenotypically normal. However deficient mice display a partial loss in the conversion of leukotriene D4 to leukotrience E4 and in the conversion of cys-bis-gly to cysteine and glycine (PubMed:9560193). Deficient mice display reduces mortality in models of sepsis (PubMed:31442408).|||Expressed in heart, lung, skeletal muscle, kidney, liver, and testis. Not detected in brain and spleen.|||Homodimer; disulfide-linked.|||Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4 (PubMed:12738806, PubMed:31442408, PubMed:9560193). Hydrolyzes cystinyl-bis-glycine (cys-bis-gly) formed during glutathione degradation (PubMed:12738806, PubMed:9560193). Possesses also beta lactamase activity and hydrolytically inactivates beta-lactam antibiotics (PubMed:12738806).|||Independently of its dipeptidase activity, acts as an adhesion receptor for neutrophil recruitment from bloodstream into inflamed lungs and liver.|||Inhibited by L-penicillamine. Inhibited by cilastatin.|||microvillus membrane http://togogenome.org/gene/10090:Prune1 ^@ http://purl.uniprot.org/uniprot/Q8BIW1 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by magnesium ions and inhibited by manganese ions. Inhibited by dipyridamole, moderately sensitive to IBMX and inhibited by vinpocetine (By similarity).|||Belongs to the PPase class C family. Prune subfamily.|||Binds 2 manganese ions per subunit.|||Cytoplasm|||Homooligomer. Able to homodimerize via its C-terminal domain. Interacts with NME1. Interacts with GSK3; at focal adhesion complexes where paxillin and vinculin are colocalized. Interacts with alpha and beta tubulin.|||In the developing embryo, a high level of expression is confined to the nervous system particularly in the dorsal root ganglia, cranial nerves, and neural retina. From 10.5 dpc, expressed at low levels in the basal plate along the entire neural tube, while at 12.5 dpc the expression in the nervous system is definitively stronger, especially in the cranial and dorsal root ganglia and in the spinal nerves. In the hypothalamus, the expression is confined to the retro-chiasmatic area (RCH) and is also detectable in the remnant of the Rathke's pouch. In the developing eye, exclusively expressed in the prospective neural retina, equally distributed in both the deep and superficial layers. At 16.5 dpc, expression is still detectable in the outer neuroblast layer of the neural retina.|||Nucleus|||Phosphodiesterase (PDE) that has higher activity toward cAMP than cGMP, as substrate. Plays a role in cell proliferation, migration and differentiation, and acts as a negative regulator of NME1. Plays a role in the regulation of neurogenesis. Involved in the regulation of microtubule polymerization.|||focal adhesion http://togogenome.org/gene/10090:Tnni2 ^@ http://purl.uniprot.org/uniprot/P13412 ^@ Function|||Similarity|||Subunit ^@ Belongs to the troponin I family.|||Binds to actin and tropomyosin.|||Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. http://togogenome.org/gene/10090:Siva1 ^@ http://purl.uniprot.org/uniprot/O54926 ^@ Cofactor|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds through its N-terminal region to the C-terminus of CD27 and to PXMP2/PMP22. Binds to the C-terminus of TNFRSF18/GITR. Isoform 1 binds to BCL2L1/BCLX isoform Bcl-x(L) but not to BAX.|||By p53, camptothecin, stroke injury and infection with coxsackievirus B3. This up-regulation is sufficient to induce apoptosis in neural tissue.|||Cytoplasm|||Highly expressed in testis, heart, liver, lung, and muscle, and less in kidney, spleen and brain.|||Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits activation of NF-kappa-B and promotes T-cell receptor-mediated apoptosis (By similarity).|||Isoform 1 binds 3 zinc ions. Isoform 2 binds 2 zinc ions.|||Mouse isoform 2 has been shown to have no pro-apoptotic activity.|||Nucleus|||Phosphorylated by ABL2/ARG in response to oxidative stress. http://togogenome.org/gene/10090:Mat2b ^@ http://purl.uniprot.org/uniprot/Q99LB6 ^@ Function|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the dTDP-4-dehydrorhamnose reductase family. MAT2B subfamily.|||Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain. Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain. NADP binding increases the affinity for MAT2A.|||Intron retention.|||Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine. Can bind NADP (in vitro). http://togogenome.org/gene/10090:Eps8l3 ^@ http://purl.uniprot.org/uniprot/Q91WL0 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EPS8 family.|||Cytoplasm|||Detected in embryonic gut. Detected in adult testis, placenta, adrenal gland and intestine.|||Interacts with ABI1. Part of a complex that contains SOS1, ABI1 and EPS8L2. Interacts with FASLG (By similarity). http://togogenome.org/gene/10090:Fgf13 ^@ http://purl.uniprot.org/uniprot/A0A7U3JW69|||http://purl.uniprot.org/uniprot/P70377 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Conditional knockout mice lacking fgf13 in the cerebral cortex or mice lacking fgf13 in most tissues display similar phenotypes of impaired spatial acquisition and memory. The cued memory and the capacity of novel object recognition are altered. They also display anxiety-related and reduced depression-like behaviors. This is associated with a disorganization of cortical structure and neural circuits. The laminar formation of the neocortex is delayed and the hippocampal development is also affected.|||Cytoplasm|||Detected in brain, eye and heart. In brain, the different isoforms display different patterns of expression. Expressed in brain and heart (at protein level). Isoform 3 is highly expressed in cardiac myocytes while isoform 1 is the most abundant in brain.|||Expressed in the subplate of the embryonic cortex and the axonal tracts in the intermediate zone, and in axonal tracts of projection neurons, specifically in the corticothalamic tract and the corpus callosum (at protein level). Isoform 2 is transiently expressed in the neocortex and hippocampus from 17 dpc to P7 (at protein level). In embryonic brain, present in all divisions of the central and peripheral nervous system and it is at least 5 times more abundant than other FHFs. Detected in the subplate, ganglionic eminences, and proliferative zones of the cortical wall at 14 dpc. Detected in the cortical plate of the cerebral cortex, hippocampus, and striatum from 17 dpc to P14. Expression is markedly reduced in adult brain where it is most abundant in hippocampus. Also detected in developing kidney. Expressed in developing chandelier neurons.|||Interacts with SCN8A; regulates SCN8A activity (By similarity). Interacts with SCN1A; may regulate SCN1A activity (By similarity). Interacts with SCN5A; the interaction is direct and may regulate SNC5A density at membranes and function (PubMed:21817159). May also interact with SCN2A and SCN11A (By similarity). Interacts with MAPK8IP2; may regulate the MAPK8IP2 scaffolding activity (PubMed:11378392).|||May be phosphorylated.|||Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules (PubMed:22726441). Through its action on microtubules, may participate to the refinement of axons by negatively regulating axonal and leading processes branching (PubMed:22726441). Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus (PubMed:22726441). Regulates voltage-gated sodium channel transport and function (PubMed:21817159). May also play a role in MAPK signaling (PubMed:11378392, PubMed:12244047). Required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons (PubMed:30679375).|||Nucleus|||Seems not to be involved in neuroblast polarization and migration but regulates axon branching.|||dendrite|||filopodium|||growth cone|||sarcolemma http://togogenome.org/gene/10090:Pycard ^@ http://purl.uniprot.org/uniprot/Q54AA2|||http://purl.uniprot.org/uniprot/Q9EPB4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Lys-63'-linked polyubiquitination by TRAF3 is critical for speck formation and inflammasome activation.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in small intestine, colon, thymus, spleen, brain, heart, skeletal muscle, kidney, lung and liver.|||Functions as key mediator in apoptosis and inflammation (PubMed:32424362, PubMed:34678144). Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner (By similarity). Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3 (By similarity). Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes (NLRP2, NLRP3, NLRP6 and AIM2) which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:32424362, PubMed:34678144, PubMed:15190255, PubMed:15507117, PubMed:21892172, PubMed:22555457). Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death (By similarity). The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions (By similarity). Clustered PYCARD nucleates the formation of caspase-1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization (By similarity). In the NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1 (By similarity). In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation (By similarity). May be involved in RIGI-triggered pro-inflammatory responses and inflammasome activation (By similarity). In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8 (PubMed:22555457). In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form (By similarity). Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways (By similarity). For regulation of NF-kappa-B activating and inhibiting functions have been reported (By similarity). Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK (By similarity). Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing (By similarity). Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590).|||Increased resistance to endotoxic shock and severe defects in caspase-1 activation and interleukin-1 beta and interleukin-18 production in macrophages in response to several pro-inflammatory molecules (PubMed:15190255, PubMed:15507117). Mutants are resitant to vaccinia virus (VACV) but not vesicular somatitis virus (VSV) infection. They show lower viral loads in the lungs compared to wild type mice, they produce higher levels of type I IFN, IL6 and RSAD2/Viperin after VCAV INFECTION (PubMed:28314590).|||Inflammasome|||Mitochondrion|||Nucleus|||Phosphorylated.|||Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta secretion (By similarity). Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height (By similarity). Component of several inflammasomes containing one pattern recognition receptor/sensor, such as NLRP2, NLRP3, NLRP6, NLRC4, AIM2, MEFV or NOD2, and probably NLRC4 or NLRP12 (PubMed:32424362, PubMed:34678144). Major component of the ASC pyroptosome, a 1-2 um supramolecular assembly (one per macrophage cell) which consists of oligomerized PYCARD dimers and CASP1 (By similarity). Interacts with CASP1 (precursor form); the interaction induces activation of CASP1 leading to the processing of interleukin-1 beta; PYCARD competes with RIPK2 for binding to CASP1 (By similarity). Interacts with NLRP3; the interaction requires the homooligomerization of NLRP3 (PubMed:30487600). Interacts with NLRP2, NLRC4, MEFV, CARD16, AIM2, NOD2, RIGI, RIPK2, PYDC1, PYDC2, NLRP10, CHUK, IKBKB and BAX (By similarity). Interacts with CASP8 (PubMed:22555457). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287).|||Strongly expressed at 9.5 dpc in the telencephalon, thalamic areas of the diencephalon, heart and liver.|||The CARD domain mediates interaction with CASP1 and NLRC4.|||The pyrin domain mediates homotypic interactions with pyrin domains of proteins such as of NLRP3, PYDC1, PYDC2 and AIM2. http://togogenome.org/gene/10090:Atp5h ^@ http://purl.uniprot.org/uniprot/Q9DCX2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase d subunit family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding (PubMed:32973183).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Tmem203 ^@ http://purl.uniprot.org/uniprot/Q8R235 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum membrane|||Interacts with ATP2A2, ITPR3 and STIM1.|||Involved in the regulation of cellular calcium homeotasis (PubMed:25996873). Required for spermatogenesis (PubMed:25996873).|||Male mutants are sterile and exhibit a profound defect in spermatogenesis and spermagiogenesis. http://togogenome.org/gene/10090:Aqp11 ^@ http://purl.uniprot.org/uniprot/Q8BHH1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MIP/aquaporin (TC 1.A.8) family. AQP11/AQP12 subfamily.|||Cell membrane|||Channel protein that facilitates the transport of water, glycerol and hydrogen peroxide across membrane of cell or organelles guaranteeing intracellular homeostasis in several organes like liver, kidney and brain (PubMed:21118806, PubMed:21251984). In situation of stress, participates in endoplasmic reticulum (ER) homeostasis by regulating redox homeostasis through the transport of hydrogen peroxide across the endoplasmic reticulum membrane thereby regulating the oxidative stress through the NADPH oxidase 2 pathway (PubMed:23275615, PubMed:30656220). Plays a role by maintaining an environment suitable for translation or protein foldings in the ER lumen namely by participating in the PKD1 glycosylation processing resulting in regulation of PKD1 membrane trafficking thereby preventing the accumulation of unfolding protein in ER (PubMed:24854278, PubMed:18606867). Plays a role in the proximal tubule function by regulating its endosomal acidification (PubMed:16107722). May play a role in postnatal kidney development (PubMed:18701606, PubMed:23486012, PubMed:27582095).|||Cytoplasm|||Cytoplasmic vesicle membrane|||Endoplasmic reticulum membrane|||Highly expressed in the S1 proximal tubule segment, (PubMed:23486012). Expressed in the testis, kidney, and liver. Weakly expressed in the heart, brain, and muscle. Highly expressed in the testis. Expressed in the proximal tubule of the cortex of 8-day-old mouse kidney (PubMed:16107722). Expressed in retina specifically at retinal Mueller glial cells (PubMed:27107718). Expressed in brain. Expressed abundantly at the choroid plexus but also expressed weakly in the parenchyma. Expressed at the capillary endothelium in the cerebral white matter (PubMed:27258268). Expressed in adult testis, in the elongated spermatids (ES) and in residual bodies inside Sertoli cells (PubMed:19812234).|||Homodimer; disulfide-linked (PubMed:16107722, PubMed:21118806). Can also form homomultimer (PubMed:21118806).|||Homozygous Aqp11 knockout mice are born normally at the expected Mendelian frequency and are normal. However, after 15 days mice begin dying, and only 15% survive until day 60. Mice exhibit severe renal dysfunction with a significant increase of blood urea nitrogen (BUN) level. The kidneys are large and pale with rough texture occupying the whole abdominal cavity. The kidneys are anemic and polycystic following swelling and vacuolization of the proximal tubule (PubMed:18701606, PubMed:16107722). Mice with conditional knockout of Aqp11 in liver appear to have a normal life span of more than 1 year, are fertile (both females and males), show a normal growth rate, and do not show any behavioral abnormalities. Unchallenged mice have normal longevity, their livers appear normal, and reveal only a minor defect in lipid handling. In contrast, rough endoplasmic reticulum (RER)-derived vacuoles develop rapidly in the periportal hepatocytes of liver-specific following 24 hours of fasting and refeeding (PubMed:23275615). Mice with temporal conditional knockout of Aqp11 between post natal days (P) P2 and P12 exhibit apparently normal kidneys at birth and within the first two postnatal weeks of life exhibit tubular dilations. When conditional knockout of Aqp11 is induced until P8, proximal tubule (PT) cell vacuolization and apparent tubular cysts are formed, whereas no deficient renal development are observed if conditional knockout of Aqp11 starts at P12 (PubMed:27582095).|||Increased by glucose (PubMed:23486012). Decreased by phlorizin (PubMed:23486012).|||Mainly expressed at the brain surface with a slight expression in the brain parenchyma at postnatal day 1, 7, and 14. At the stage of postnatal day 28, mainly expressed in the parenchyma.|||Not glycosylated.|||The NPC motif is essential for oligomerization and water permeability function.|||perinuclear region http://togogenome.org/gene/10090:Tusc3 ^@ http://purl.uniprot.org/uniprot/Q8BTV1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory component of the STT3B-containing form of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. OST can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes. The association of TUSC3 or MAGT1 with the STT3B-containing complex seems to be mutually exclusvice.|||Acts as accessory component of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues; in this function seems to act redundantly with MAGT1. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Has also oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition.|||Belongs to the OST3/OST6 family.|||Endoplasmic reticulum membrane|||Magnesium transporter. http://togogenome.org/gene/10090:Ocm ^@ http://purl.uniprot.org/uniprot/P51879 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the parvalbumin family.|||Found in tumor tissues and not detected in normal tissues.|||Has some calmodulin-like activity with respect to enzyme activation and growth regulation. Binds two calcium ions. http://togogenome.org/gene/10090:Gpx5 ^@ http://purl.uniprot.org/uniprot/P21765|||http://purl.uniprot.org/uniprot/Q496Q2|||http://purl.uniprot.org/uniprot/Q8CC60|||http://purl.uniprot.org/uniprot/Q8CDQ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glutathione peroxidase family.|||Epididymis.|||Protects cells and enzymes from oxidative damage, by catalyzing the reduction of hydrogen peroxide, lipid peroxides and organic hydroperoxide, by glutathione. May constitute a glutathione peroxidase-like protective system against peroxide damage in sperm membrane lipids.|||Secreted http://togogenome.org/gene/10090:Med28 ^@ http://purl.uniprot.org/uniprot/Q920D3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 28 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May be part of a complex containing NF2/merlin that participates in cellular signaling to the actin cytoskeleton downstream of tyrosine kinase signaling pathways (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Forms a ternary complex with NF2/merlin and GRB2. Binds to actin (By similarity).|||Cytoplasm|||Membrane|||Nucleus http://togogenome.org/gene/10090:Tmem100 ^@ http://purl.uniprot.org/uniprot/Q9CQG9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Endoplasmic reticulum|||Expressed in dorsal root ganglia. Expressed in neurons as well as nerve fiber bundles connecting ganglia and fibers innervating muscle layer of the gastric body, jejunum, and proximal colon. Expressed in arterial endothelial cells and neurons of the central nervous system and peripheral nervous system (at protein level). Expressed strongly in lung, weakly in brain, heart and muscle. Expressed in enteric neurons and vascular tissue in the muscularis propria of the gastrointestinal tract.|||Expressed in embryo at 8.5 dpc. Expressed in arterial endothelial cells of the pharyngeal arch artery and endocardium at 9.5 dpc, onward. Expressed in dorsal aorta, pharyngeal arch and primitive internal carotid arteries at 11.5 dpc. Expressed also in intersomitic, mesenchephalic, metencephalic and anterior choroidal arteries at 12.5 dpc. Expressed in the ventral neural tube of the embryo.|||Interacts (via C-terminus) with TRPA1 and TRPV1 (PubMed:25640077). Interacts with TASOR (PubMed:31112734).|||Membrane|||Mice die at a mid- or late-gestational period. Show embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis (PubMed:22783020). Conditional knockout in endothelial cells show similar vascular defects to those observed in global null mice (PubMed:20848592, PubMed:22783020). Conditional knockout mice lacking Tmem100 in dorsal root ganglia (DRG) primary sensory neurons, exhibit normal mechanical sensitivity but reduced acute nocifensive behaviors induced by mustard oil, consistent with a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain (PubMed:25640077).|||Perikaryon|||Plays a role during embryonic arterial endothelium differentiation and vascular morphogenesis through the ACVRL1 receptor-dependent signaling pathway upon stimulation by bone morphogenetic proteins, such as GDF2/BMP9 and BMP10 (PubMed:22783020). Involved in the regulation of nociception, acting as a modulator of the interaction between TRPA1 and TRPV1, two molecular sensors and mediators of pain signals in dorsal root ganglia (DRG) neurons (PubMed:25640077). Mechanistically, it weakens their interaction, thereby releasing the inhibition of TRPA1 by TRPV1 and increasing the single-channel open probability of the TRPA1-TRPV1 complex (PubMed:25640077).|||perinuclear region http://togogenome.org/gene/10090:Fto ^@ http://purl.uniprot.org/uniprot/Q8BGW1 ^@ Activity Regulation|||Caution|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by ascorbate (PubMed:17991826). Inhibited by N-oxalylglycine, fumarate and succinate (PubMed:17991826).|||Belongs to the fto family.|||Binds 1 Fe(2+) ion per subunit.|||Cytoplasm|||Down-regulated in fasting animals.|||Elevated perinatal mortality (PubMed:19234441). Mice have normal body weight at birth, but show growth retardation from day 2 onwards, resulting in a weight reduction of 30-40% after 6 weeks, both in males and females (PubMed:19234441). In addition, animals display reduced nose to anus length (PubMed:19234441). Fat mass is reduced by 60% in males and by 23% in females (PubMed:19234441). Lean body mass is reduced by 26% in males and 19% in females (PubMed:19234441). White adipose tissue decreases more and more over time, while brown adipose tissue is not affected (PubMed:19234441). Serum leptin levels are decreased, while serum levels of adiponectin are increased (PubMed:19234441). Mice exhibit significant hyperphagia after correction for body weight (PubMed:19234441). They show increased oxygen consumption, carbon dioxide production and heat generation, indicating increased energy expenditure, in spite of reduced spontaneous locomotor activity (PubMed:19234441). Plasma adrenaline concentrations are significantly increased (PubMed:19234441). Overall glucose metabolism appears normal (PubMed:19234441). Conditional deletion in the adult affects body composition and metabolism, and causes a small reduction in food intake and weight gain (PubMed:23300482). Mice with conditional deletion in dopaminergic neurons show abnormal dopamine signaling pathways, including impaired dopamine receptor type 2 (D2R) and type 3 (D3R) signaling and the related locomotion function (PubMed:23817550). Deficient mice show increased N(6)-methyladenosine (m6A) in a subset of mRNAs important for neuronal signaling, including many in the dopaminergic signaling pathway (PubMed:23817550). Knockout cells show strongly increased levels of N(6),2'-O-dimethyladenosine cap (m6A(m)) mRNAs (PubMed:28002401).|||Many publications have reported a critical role of Fto in regulating fat mass, adipogenesis and total body weight (PubMed:19234441, PubMed:19680540, PubMed:21076408, PubMed:23817550, PubMed:23300482). However, some reports suggest that some effects are indirect and caused by impaired expression of adjacent genes such as Irx3 and Rpgrip1l (PubMed:24807221, PubMed:24646999).|||Monomer (PubMed:19680540). May also exist as homodimer (PubMed:19680540).|||Nucleus|||Nucleus speckle|||RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:17991826, PubMed:18775698, PubMed:28002401). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:28002401). M6A demethylation by FTO affects mRNA expression and stability (By similarity). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (By similarity). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:28002401). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (By similarity). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (By similarity). Has no activity towards 1-methylguanine (By similarity). Has no detectable activity towards double-stranded DNA (By similarity). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:17991826, PubMed:18775698). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:17991826, PubMed:18775698). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:19234441, PubMed:19680540, PubMed:21076408, PubMed:23817550, PubMed:23300482). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:19234441, PubMed:19680540). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (PubMed:23817550).|||The 3D-structure of the Fe2OG dioxygenase domain is similar to that of the Fe2OG dioxygenase domain found in the bacterial DNA repair dioxygenase alkB and its mammalian orthologs, but sequence similarity is very low. As a consequence, the domain is not detected by protein signature databases.|||Ubiquitous. Detected in brain, brain cortex, hypothalamus, cerebellum, liver, pancreas, heart, kidney, white adipose tissue and skeletal muscle. Most abundant in the brain, particularly in hypothalamic nuclei governing energy balance. http://togogenome.org/gene/10090:Nod1 ^@ http://purl.uniprot.org/uniprot/Q8BHB0 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although ubiquitously expressed, NOD1 levels are more abundant in immune cells, the gastrointestinal tract, and adipose tissue.|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the NOD1-NOD2 family.|||Cell membrane|||Cytoplasm|||Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes NOD1-RIPK2 RIPosome recruitment to autophagosome membranes, promoting their SQSTM1/p62-dependent autophagic degradation.|||Homooligomer: homooligomerizes following ligand-binding, promoting RIPK2 recruitment (By similarity). Interacts (via CARD domain) with RIPK2 (via CARD domain) (By similarity). Following RIPK2 recruitment, RIPK2 homooligomerizes via its CARD domain and forms long filaments named RIPosomes (By similarity). Interacts (via CARD domain) with ubiquitin; inhibiting interaction with RIPK2 (By similarity). Interacts with ARHGEF2 (By similarity). Interacts with NLRP10 and recruits it to the cell membrane following invasive bacterial infection (By similarity). Interacts with IFIH1; this interaction promotes transcription of antiviral genes and inhibition of viral replication (By similarity). Interacts with Irgm1; promoting NOD1 degradation (By similarity). Interacts with ATG16L1 (PubMed:19898471).|||Human and mouse NOD1 bind gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) in a different context (PubMed:16211083). do not detect the same muropeptide from bacterial peptidoglycan: while human NOD1 detects a tripeptide-containing muropeptide (MurNAc-TriDAP or TriDAP), mouse Nod1 needs a tetrapeptide structure for efficient sensing (MurNAc-tetraDAP or TetraDAP) (PubMed:16211083).|||No visible phenotype in absence of infection (PubMed:12796777). Mice however show impaired cytokine secretion in response to bacterial infection: macrophages do not secrete cytokines in response to synthetic gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and do not prime the lipopolysaccharide response (PubMed:12796777). Deletion mutant mice show a normal glucose tolerance but the level of circulating insulin after glucose infusion was significantly lower than in wild-type mice (PubMed:31201384). Mice lacking Nod1 and Nod2 are protected from high-fat diet-induced inflammation, lipid accumulation, and peripheral insulin intolerance (PubMed:21715553).|||Palmitoylated. Palmitoylation is required for proper recruitment to the bacterial entry site and hence for proper signaling upon cognate peptidoglycan detection.|||Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and thus participates in both innate and adaptive immune responses (PubMed:12796777, PubMed:21715553). Specifically recognizes and binds gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), a dipeptide present in peptidoglycan of Gram-negative bacteria (PubMed:12796777, PubMed:16211083). Preferentially binds iE-DAP in tetrapeptide-containing muropeptides (MurNAc-TetraDAP or TetraDAP) (PubMed:16211083). Ligand binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2 (By similarity). Following recruitment, RIPK2 undergoes 'Met-1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin-protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a scaffolding protein for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling (By similarity). This in turn leads to the transcriptional activation of hundreds of genes involved in immune response (By similarity). Also acts as a regulator of antiviral response elicited by dsRNA and the expression of RLR pathway members by targeting IFIH1 and TRAF3 to modulate the formation of IFIH1-MAVS and TRAF3-MAVS complexes leading to increased transcription of type I IFNs (By similarity). Also acts as a regulator of autophagy via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry (PubMed:19898471). Besides recognizing pathogens, also involved in the endoplasmic reticulum stress response: acts by sensing and binding to the cytosolic metabolite sphingosine-1-phosphate generated in response to endoplasmic reticulum stress, initiating an inflammation process that leads to activation of the NF-kappa-B and MAP kinases signaling (PubMed:27007849). In addition, plays a role in insulin trafficking in beta cells in a cell-autonomous manner (PubMed:21715553, PubMed:31201384). Mechanistically, upon recognizing cognate ligands, NOD1 and RIPK2 localize to insulin vesicles where they recruit RAB1A to direct insulin trafficking through the cytoplasm (PubMed:31201384).|||Ubiquitinated. 'Lys-48'-linked polyubiquitination by RNF34 promotes proteasomal degradation and thereby negatively regulates NOD1 for instance in NF-kappa-B activation. http://togogenome.org/gene/10090:Or2av9 ^@ http://purl.uniprot.org/uniprot/Q5NC45 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Spp2 ^@ http://purl.uniprot.org/uniprot/Q8K1I3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SPP2 family.|||Could coordinate an aspect of bone turnover.|||Phosphorylation sites are present in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Gm20822 ^@ http://purl.uniprot.org/uniprot/J3KMI7 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Ang ^@ http://purl.uniprot.org/uniprot/P21570|||http://purl.uniprot.org/uniprot/Q3TBG7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the pancreatic ribonuclease family.|||Homodimer. Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur (By similarity).|||Ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs) (PubMed:19114040, PubMed:33986151). Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus (By similarity). Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA (By similarity). Angiogenin induces vascularization of normal and malignant tissues (By similarity). Angiogenic activity is regulated by interaction with RNH1 in vivo (By similarity).|||Secreted|||nucleolus|||secretory vesicle lumen http://togogenome.org/gene/10090:Il18bp ^@ http://purl.uniprot.org/uniprot/Q9Z0M9 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Binds to IL-18 and inhibits its activity. Functions as an inhibitor of the early TH1 cytokine response (By similarity).|||Intron retention.|||Secreted http://togogenome.org/gene/10090:Pkp2 ^@ http://purl.uniprot.org/uniprot/Q9CQ73 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the beta-catenin family.|||Cell junction|||Cytoplasm|||Expressed in cardiomyocytes of the atrium and ventricle of the heart in embryos at 10.75 and 13.75 dpc.|||Expressed in heart (at protein level).|||Interacts with DSC2 (By similarity). Interacts with JUP (By similarity). Interacts with KRT5/CK5, KRT8/CK8, KRT14/CK14, KRT18/CK18 and VIM (By similarity). Interacts (via N-terminus) with MARK3/C-TAK1 (By similarity). Interacts with DSP (By similarity). Interacts with DSG1, DSG2 and DSG3 (By similarity). Interacts (via N-terminus) with CTNNB1 (By similarity). Interacts with CDH1 (By similarity). Interacts with the RNA polymerase III (Pol III) complex proteins POLR3A/RPC155, POLR3F/RPC39 and POLR3C/RPC82 (By similarity). Interacts with CTNNA3 (By similarity). Interacts (via N-terminus) with SCN5A/Nav1.5 (By similarity).|||Knockout mice die during embryogenesis (PubMed:15479741). Embryos show accumulation of blood in the pericardial and peritoneal cavities, and absence in the head, dorsal trunk and yolk sac at 10.75 dpc followed by a significant decrease in viable embryos at 11.5 dpc (PubMed:15479741). Embryonic heart formation is abnormal showing reduced trabeculation in the heart ventricles and thinning of the atria walls (PubMed:15479741). Loss of DSP and DSG2 localization at cell-cell junctions in cardiomyocytes, DSP localizes to granular aggregates in the cytoplasm which are surrounded by disordered swirls of intermediate filaments (PubMed:15479741). Loss of fascia adherens-like and desmosome-like cell junctions at the intercalated disks (PubMed:15479741).|||Nucleus|||Regulates focal adhesion turnover resulting in changes in focal adhesion size, cell adhesion and cell spreading, potentially via transcriptional modulation of beta-integrins (By similarity). Required to maintain gingival epithelial barrier function (By similarity). Required for cardiac sodium current propagation and electrical synchrony in cardiac myocytes (By similarity). Required for the formation of desmosome cell junctions in cardiomyocytes, thereby required for the correct formation of the heart, specifically trabeculation and formation of the atria walls (PubMed:15479741). Loss of desmosome cell junctions leads to mis-localization of DSP and DSG2 resulting in disruption of cell-cell adhesion and disordered intermediate filaments (PubMed:15479741). Modulates profibrotic gene expression in cardiomyocytes via regulation of DSP expression and subsequent activation of downstream TGFB1 and MAPK14/p38 MAPK signaling (By similarity). May play a role in junctional plaques (By similarity).|||desmosome http://togogenome.org/gene/10090:Timm8a1 ^@ http://purl.uniprot.org/uniprot/Q9WVA2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small Tim family.|||Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22 (By similarity).|||Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins (By similarity).|||Mitochondrion inner membrane|||Present at high level in liver and brain, and at lower level in muscle and heart. In CNS sections, it is predominantly present in the soma and the dendritic portion of the Purkinje cells of the cerebellum, but not in the glial cells. Scattered expression also is also detected in the brain stem, olfactory bulb, substantia nigra, hippocampus and striatum (at protein level). Ubiquitously expressed.|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). http://togogenome.org/gene/10090:Bend6 ^@ http://purl.uniprot.org/uniprot/Q6PFX2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a corepressor of recombining binding protein suppressor hairless (RBPJ) and inhibits Notch signaling in neural stem cells, thereby opposing their self-renewal and promoting neurogenesis (PubMed:23571214, PubMed:25561495).|||Expressed in differentiating neurons in embryonic neocortex (at protein level).|||Interacts (via BEN domain) with RBPJ.|||Nucleus http://togogenome.org/gene/10090:Mageb4 ^@ http://purl.uniprot.org/uniprot/A2A9R3 ^@ Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Detected between 13.5 and 14.5 dpc in both female and male gonads (at protein level). Increases in the male gonads and intensely expressed before birth (at protein level). In female gonads, remains constant until birth (at protein level). In testis, specifically expressed in premeiotic germ cells (at protein level). In fetal ovary, expressed in both premeiotic germ cells, and germ cells that have gone through the pachytene phase and entered meiotic arrest (at protein level).|||Expressed in testis (at protein level). http://togogenome.org/gene/10090:Or5d41 ^@ http://purl.uniprot.org/uniprot/Q8VFG1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcsk7 ^@ http://purl.uniprot.org/uniprot/Q61139 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S8 family.|||Inhibited by zinc and copper.|||Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive secretory pathway.|||Ubiquitously expressed at constitutive levels during embryogenesis.|||Widely expressed. Expressed in brain, lung, muscle, heart, liver, kidney, spleen and thymus.|||trans-Golgi network membrane http://togogenome.org/gene/10090:A2ml1 ^@ http://purl.uniprot.org/uniprot/Q3TTY9|||http://purl.uniprot.org/uniprot/Q3UU35 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.|||Homotetramer.|||Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism.|||Secreted http://togogenome.org/gene/10090:Or5h18 ^@ http://purl.uniprot.org/uniprot/Q8VEX5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:3110040N11Rik ^@ http://purl.uniprot.org/uniprot/Q9CRC3 ^@ Similarity ^@ Belongs to the UPF0235 family. http://togogenome.org/gene/10090:Crtam ^@ http://purl.uniprot.org/uniprot/Q149L7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nectin family.|||Cell membrane|||In the immune system, expression is restricted to activated class-I MHC-restricted cells, including NKT, NK and CD8+ T-cells (at protein level) (PubMed:10811014, PubMed:15811952, PubMed:18329370, PubMed:19752223). Transiently expressed in activated CD8+ T-cells and a subset of activated CD4+ T-cells (at protein level) (PubMed:18329370). Expressed in activated intestinal T-cells, specifically intraepithelial CD4+ CD8+ T-cells, intraepithelial CD4+ T-cells and, CD8+ T-cells in the intestine epithelium, lamina propria, Peyer's Patches and mesenteric lymph nodes (PubMed:24687959). Also expressed in spleen, brain and testis (PubMed:10811014).|||Mediates heterophilic cell-cell adhesion which regulates the activation, differentiation and tissue retention of various T-cell subsets (PubMed:15811952, PubMed:18329370, PubMed:19752223, PubMed:24687959). Interaction with CADM1 promotes natural killer (NK) cell cytotoxicity and IFNG/interferon-gamma secretion by CD8+ T-cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM1 in vivo (PubMed:15811952). Regulates CD8+ T-cell proliferation in response to T-cell receptor (TCR) activation (PubMed:18329370). Appears to be dispensable for CD8+ T-cell-mediated cytotoxicity (PubMed:19752223). Interaction with SCRIB promotes the late phase of cellular polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG, IL17 and IL22 production (PubMed:18329370). By interacting with CADM1 on CD8+ dendritic cells, regulates the retention of activated CD8+ T-cells within the draining lymph node (PubMed:19752223). Required for the intestinal retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent, intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells (PubMed:24687959). Interaction with CADM1 promotes the adhesion to gut-associated CD103+ dendritic cells, which may facilitate the expression of gut-homing and adhesion molecules on T-cells and the conversion of CD4+ T-cells into CD4+ CD8+ T-cells (PubMed:24687959).|||Monomer (By similarity). May form homodimer (via Ig-like V-type domain) (By similarity). Interacts (via Ig-like V-type domain) with CADM1 (via Ig-like V-type domain); the interaction competes with CRTAM homodimerization and CADM1 homodimerization (PubMed:15781451, PubMed:15811952). Interacts (via PDZ-binding motif) with SCRIB (via PDZ domain 3); the interaction promotes CRTAM and SCRIB polarization in a subset of CD4+ T-cells (PubMed:18329370).|||No visible phenotype (PubMed:18329370, PubMed:19752223). In the small intestine mucosa and under steady-state conditions, severe reduction in the number of intraepithelial CD4+ CD8+ T-cells and, partial reduction in the number of lamina propria and intraepithelial CD8+ and CD4+ T-cells (PubMed:24687959). In intestinal CD4+ T-cells, expression of gut-retention molecules Itgae/CD103 and Cd69, and gut-homing molecule Ccr9 is reduced (PubMed:24687959). Development of lymphocytes and myeloid cells is normal (PubMed:18329370, PubMed:19752223). However, in older mice, the number of CD4+ and CD8+ T-cells is increased in lymph nodes and blood (PubMed:18329370). Susceptible to oral infection with bacterium C.rodentium resulting in higher bacteria load in the colon and spleen (PubMed:18329370). However, in another study, the mice were not susceptible to oral infection with bacterium C.rodentium (PubMed:24687959). Impaired immune response following intranasal infection with influenza virus caused by a decrease in the number of antigen-specific CD8+ T-cells in the infected lung (PubMed:19752223). However, the capacity of CD8+ T-cells to kill infected cells is not affected (PubMed:19752223). Increased resistance to oral infection with intracellular parasite T.gondii caused by a reduced number of IL17-producing CD4+ T-cells resulting in enhanced clearance of the parasite (PubMed:24687959).|||The extracellular domain is required for the regulation of IFNG and IL22 production, but is dispensable for late T-cell polarization. http://togogenome.org/gene/10090:Alpk2 ^@ http://purl.uniprot.org/uniprot/Q91ZB0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Basolateral cell membrane|||Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.|||Protein kinase that recognizes phosphorylation sites in which the surrounding peptides have an alpha-helical conformation (PubMed:10021370). Regulates cardiac development and cardiomyocyte differentiation by negatively regulating Wnt/beta-catenin signaling (By similarity). http://togogenome.org/gene/10090:Manbal ^@ http://purl.uniprot.org/uniprot/A2BGN7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UPF0239 family.|||Membrane http://togogenome.org/gene/10090:Ttc9c ^@ http://purl.uniprot.org/uniprot/Q810A3 ^@ Similarity ^@ Belongs to the TTC9 family. http://togogenome.org/gene/10090:Clu ^@ http://purl.uniprot.org/uniprot/Q06890|||http://purl.uniprot.org/uniprot/Q549A5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers.|||Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers. Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ. Slightly acidic pH promotes interaction with misfolded proteins. Forms high-molecular weight oligomers upon interaction with misfolded proteins. Interacts with APOA1, LRP2, CLUAP1 and PON1. Interacts with the complement complex (By similarity). Interacts (via alpha chain) with XRCC6 (PubMed:12551933). Interacts with SYVN1, COMMD1, BTRC, CUL1 and with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. Interacts (via alpha chain) with BAX in stressed cells, where BAX undergoes a conformation change leading to association with the mitochondrial membrane. Does not interact with BAX in unstressed cells. Found in a complex with LTF, CLU, EPPIN and SEMG1. Interacts (immaturely glycosylated pre-secreted form) with HSPA5; this interaction promotes CLU stability and facilitates stress-induced CLU retrotranslocation from the secretory pathway to the mitochondria, thereby reducing stress-induced apoptosis by stabilizing mitochondrial membrane integrity. Interacts with BCL2L1; this interaction releases and activates BAX and promotes cell death. Interacts with TGFBR2 and ACVR1 (By similarity). Interacts (secreted form) with STMN3; this interaction may act as an important modulator during neuronal differentiation (By similarity). Interacts with VLDLR and LRP8 (By similarity).|||Belongs to the clusterin family.|||Cytoplasm|||Endoplasmic reticulum|||Extensively glycosylated with sulfated N-linked carbohydrates (By similarity). About 30% of the protein mass is comprised of complex N-linked carbohydrate. Endoplasmic reticulum (ER) stress induces changes in glycosylation status and increases level of hypoglycosylated forms. Core carbohydrates are essential for chaperone activity. Non-secreted forms are hypoglycosylated or unglycosylated (By similarity).|||Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins (By similarity). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:14741101). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. When secreted, protects cells against apoptosis and against cytolysis by complement. Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity (By similarity). Following stress, promotes apoptosis (PubMed:12551933). Inhibits apoptosis when associated with the mitochondrial membrane by interference with BAX-dependent release of cytochrome c into the cytoplasm. Plays a role in the regulation of cell proliferation. Following ER stress, suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5. When secreted, does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (By similarity). When secreted, acts as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (PubMed:11865066).|||Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins.|||Membrane|||Microsome|||Mitochondrion|||Mitochondrion membrane|||Most abundant in stomach, liver, brain, and testis, with intermediate levels in heart, ovary and kidney.|||No visible phenotype (PubMed:11067863, PubMed:11865066). During myocarditis, mice show an increased tendency to cardiac tissue injury (PubMed:11067863). Homozygous CLU aging mice exhibit a striking glomerulopathy characterized by progressive mesangial expansion and collapse of capillary lumens (PubMed:11865066).|||Nucleus|||Polyubiquitinated, leading to proteasomal degradation. Under cellular stress, the intracellular level of cleaved form is reduced due to proteasomal degradation.|||Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen. Proteolytic cleavage is not necessary for its chaperone activity. All non-secreted forms are not proteolytically cleaved. Chaperone activity of uncleaved forms is dependent on a non-reducing environment.|||Secreted|||chromaffin granule|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Nmu ^@ http://purl.uniprot.org/uniprot/Q059S5|||http://purl.uniprot.org/uniprot/Q9QXK8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NmU family.|||Does not function as a ligand for either NMUR1 or NMUR2. Indirectly induces prolactin release although its potency is much lower than that of neuromedin precursor-related peptide 36.|||Does not function as a ligand for either NMUR1 or NMUR2. Indirectly induces prolactin release from lactotroph cells in the pituitary gland, probably via the hypothalamic dopaminergic system.|||Ligand for receptors NMUR1 and NMUR2 (By similarity). Stimulates muscle contractions of specific regions of the gastrointestinal tract.|||Secreted|||Stimulates muscle contractions of specific regions of the gastrointestinal tract. http://togogenome.org/gene/10090:Odr4 ^@ http://purl.uniprot.org/uniprot/Q4PJX1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ODR-4 family.|||May play a role in the trafficking of a subset of G-protein coupled receptors.|||Membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Map3k12 ^@ http://purl.uniprot.org/uniprot/Q60700 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under basal conditions and dephosphorylated when membrane-associated.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Cell membrane|||Cytoplasm|||Homodimer (PubMed:8663324). Interacts with MBIP (By similarity).|||Interacts with MBIP through the leucine-zipper motif.|||Protein kinase which is part of a non-canonical MAPK signaling pathway (PubMed:7983011, PubMed:8663324, PubMed:28111074). Activated by APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and MAPK3/ERK1 (PubMed:28111074). May be an activator of the JNK/SAPK pathway.|||The activity of MAP3K12 can be regulated through its proteasomal degradation. APOE, through a receptor-mediated mechanism, activates MAP3K12 by preventing its proteasomal degradation.|||Within the nervous system, predominantly expressed in neurons and enriched in synaptic terminals (PubMed:8663324). Expressed in brain, kidney, lung, heart, testis, gastrointestinal tract, stomach, liver and pancreas (PubMed:8769565, PubMed:7983011). http://togogenome.org/gene/10090:Txnrd3 ^@ http://purl.uniprot.org/uniprot/Q3UY43|||http://purl.uniprot.org/uniprot/Q99MD6 ^@ Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates in the testis after puberty. Not detected in 20-day-old mice but highly expressed in testes of 7-month-old mice.|||Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.|||Binds 1 FAD per subunit.|||Cytoplasm|||Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components.|||Endoplasmic reticulum|||Expressed preferentially in testis where it is found in spermatids and spermatocytes but not in sperm. In elongating spermatids, expressed at the site of mitochondrial sheath formation. Low levels in other tissues including heart, lung, liver, kidney, brain, muscle and prostate.|||Homodimer.|||Microsome|||Nucleus|||The N-terminal glutaredoxin domain does not contain the C-X-X-C redox-active motif normally found in glutaredoxins but activity may be mediated through a single cysteine. The C-terminal Cys-Sec motif of one subunit of the homodimer may transfer electrons from the thiol-disulfide center to the glutaredoxin domain of the other subunit.|||The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity (By similarity).|||This sequence initiates at a CTG codon.|||Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon. http://togogenome.org/gene/10090:Nes ^@ http://purl.uniprot.org/uniprot/Q6P5H2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Constitutively phosphorylated. This increases during mitosis when the cytoplasmic intermediate filament network is reorganized (By similarity).|||Embryonic lethality with the neuroepithelium of developing neural tube exhibiting low numbers of neural stem cells and high levels of apoptosis. No effect on cytoskeletal integrity.|||Forms homodimers and homotetramers in vitro. In mixtures with other intermediate filament proteins such as vimentin and alpha-internexin, this protein preferentially forms heterodimers which can assemble to form intermediate filaments if nestin does not exceed 25%. Interacts with FHOD3 (By similarity).|||Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division (By similarity). Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells. http://togogenome.org/gene/10090:Peg3 ^@ http://purl.uniprot.org/uniprot/Q3URU2 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Brain, glial cells, neurons, skeletal muscle, uterus and placenta. In the placenta it is found in all trophoblast cells.|||Cytoplasm|||Homodimer. Interacts with SIAH1A and SIAH2. Interacts with TRAF2.|||Induced during p53/TP53 mediated apoptosis. Up-regulated by DNA damage in cortical neurons in the presence of p53/TP53.|||Induces apoptosis in cooperation with SIAH1A. Acts as a mediator between p53/TP53 and BAX in a neuronal death pathway that is activated by DNA damage. Acts synergistically with TRAF2 and inhibits TNF induced apoptosis through activation of NF-kappa-B. Plays a role in regulating maternal behavior and offspring growth.|||Nucleus|||Strongly expressed upon gastrulation and subsequently becomes restricted to skeletal muscle and subregions of the CNS. At 9.5 dpc, expressed in the branchial arches, somites and gut but little in the heart and neural tissues. At 12.5 dpc strongly expressed in the cranial skeleton, tongue, vertebral cartilage, pituitary and the luminal epithelium.|||The SCAN domain enables PEG3 homo- or heterodimerization to control gene expression in a combinatorial fashion. http://togogenome.org/gene/10090:Ap1s2 ^@ http://purl.uniprot.org/uniprot/Q3TIV9|||http://purl.uniprot.org/uniprot/Q8BW87|||http://purl.uniprot.org/uniprot/Q9DB50 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Binds to MUC1 (By similarity).|||Belongs to the adaptor complexes small subunit family.|||Cytoplasmic vesicle membrane|||Golgi apparatus|||Membrane|||Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules (By similarity).|||Widely expressed.|||clathrin-coated pit http://togogenome.org/gene/10090:Esrp2 ^@ http://purl.uniprot.org/uniprot/Q8K0G8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ESRP family.|||Epithelial cell-specific.|||Nucleus|||mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Also regulates the splicing of CD44, CTNND1, ENAH, 3 transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of FGFR2 (By similarity). http://togogenome.org/gene/10090:Dcdc2c ^@ http://purl.uniprot.org/uniprot/Q9D1B8 ^@ Subcellular Location Annotation ^@ Cytoplasm|||flagellum http://togogenome.org/gene/10090:Or4x18 ^@ http://purl.uniprot.org/uniprot/A2ATW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp4b ^@ http://purl.uniprot.org/uniprot/P50992|||http://purl.uniprot.org/uniprot/Q0VBB6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the X(+)/potassium ATPases subunit beta family.|||Cell membrane|||Expressed in parietal cells (at protein level).|||Membrane|||N-glycosylation is necessary for assembly and functional expression of the pump at the plasma membrane.|||The ATPase pump is composed of two subunits: alpha (catalytic) and beta (regulatory). Interacts with alpha subunit ATP12A; this interaction is required for the formation of a functionally active pump and targeting at the plasma membrane (By similarity). Interacts (via N-terminus) with alpha subunit ATP4A (via the P-domain) (By similarity).|||The C-terminal lobe folds into an immunoglobulin-like domain and mediates cell adhesion properties.|||The beta subunit of the gastric H(+)/K(+) ATPase pump which transports H(+) ions in exchange for K(+) ions across the apical membrane of parietal cells. Plays a structural and regulatory role in the assembly and membrane targeting of a functionally active pump (By similarity). Within a transport cycle, the transfer of a H(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation of the alpha subunit that shifts the pump conformation from inward-facing (E1) to outward-facing state (E2). Interacts with the phosphorylation domain of the alpha subunit and functions as a ratchet, stabilizing the lumenal-open E2 conformation and preventing the reverse reaction of the transport cycle (By similarity).|||This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. http://togogenome.org/gene/10090:Lrrc24 ^@ http://purl.uniprot.org/uniprot/Q8BHA1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ndufv1 ^@ http://purl.uniprot.org/uniprot/Q91YT0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I 51 kDa subunit family.|||Binds 1 FMN.|||Binds 1 [4Fe-4S] cluster.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits (By similarity). This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme (By similarity). Interacts with RAB5IF (PubMed:31536960).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Gpr84 ^@ http://purl.uniprot.org/uniprot/A0A0R4J100|||http://purl.uniprot.org/uniprot/Q8CIM5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By lipopolysaccharide in the monocyte/macrophage cell lines.|||Cell membrane|||Expressed predominantly in hematopoietic tissues. Expressed mainly in the bone marrow with transcripts also detected in spleen, the lymph node, liver and the lung.|||Membrane|||Receptor for medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0), undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent agonists. Not activated by short-chain and long-chain saturated and unsaturated FFAs. Activation by medium-chain free fatty acid is coupled to a pertussis toxin sensitive G(i/o) protein pathway. May have important roles in processes from fatty acid metabolism to regulation of the immune system (By similarity). http://togogenome.org/gene/10090:Gpkow ^@ http://purl.uniprot.org/uniprot/Q56A08 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MOS2 family.|||Component of the minor spliceosome, which splices U12-type introns (By similarity). Interacts with PRKX, PRKACB and DHX16.|||Nucleus|||Phosphorylation regulates its ability to bind RNA.|||RNA-binding protein involved in pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). http://togogenome.org/gene/10090:Or10ag52 ^@ http://purl.uniprot.org/uniprot/Q7TR54 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Btbd1 ^@ http://purl.uniprot.org/uniprot/P58544 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts (via C-terminus) with TOP1. Interacts with TRIM5 isoform Delta. Interacts with CUL3.|||Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Seems to regulate expression levels and/or subnuclear distribution of TOP1, via an unknown mechanism (PubMed:15486563, PubMed:17462629). May play a role in mesenchymal differentiation where it promotes myogenic differentiation and suppresses adipogenesis (PubMed:15486563, PubMed:17462629).|||Strongly expressed in heart and skeletal muscle. Weakly expressed in myoblast C2C12 cells, but strongly up-regulated upon their differentiation into myotubes. http://togogenome.org/gene/10090:Tnfsf18 ^@ http://purl.uniprot.org/uniprot/Q7TS55 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine that binds to TNFRSF18/AITR/GITR (PubMed:14521928, PubMed:14647196). Regulates T-cell responses (PubMed:14647196). Can function as costimulator and lower the threshold for T-cell activation and T-cell proliferation (PubMed:14608036, PubMed:15128759). Important for interactions between activated T-lymphocytes and endothelial cells. Mediates activation of NF-kappa-B (PubMed:14521928, PubMed:14647196, PubMed:18178614). Triggers increased phosphorylation of STAT1 and up-regulates expression of VCAM1 and ICAM1 (By similarity). Promotes leukocyte adhesion to endothelial cells (PubMed:23892569). Regulates migration of monocytes from the splenic reservoir to sites of inflammation (PubMed:24107315).|||Detected in immature and mature dendritic cells and in macrophages (at protein level). Detected in spleen, lung, heart, thymus, monocytes, macrophages, B-cells and dendritic cells.|||Homotrimer. Homodimer.|||N-glycosylated.|||Reduced levels of pro-inflammatory macrophages in the peritoneal cavity following injection with thioglycollate broth to induce peritonitis and reduced AGTR1 levels in spleen macrophages.|||Up-regulated by exposure to bacterial lipopolysaccharide (LPS). http://togogenome.org/gene/10090:Rarres1 ^@ http://purl.uniprot.org/uniprot/F6ZIS7|||http://purl.uniprot.org/uniprot/Q8BVL6 ^@ Similarity ^@ Belongs to the protease inhibitor I47 (latexin) family. http://togogenome.org/gene/10090:Epb41l5 ^@ http://purl.uniprot.org/uniprot/Q8BGS1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 10.5 dpc, strongly expressed in the developing neural tube and optic vesicle, as well as in the branchial arches and kidney (PubMed:17920587). In the developing kidney, detected in the mesonephrotic tubules (PubMed:17920587). At 11.5 dpc, expressed along the entire cranial-caudal length of the developing neural tube, including the anterior forebrain and the posterior spinal cord (PubMed:17920587). Always restricted to the ventricular layer, where proliferative cells are located (PubMed:17920587). Conversely, not detected in postmitotic neural compartments (PubMed:17920587). In the developing lung, at 11.5 dpc, expressed in the internal endodermal layer and in particular in the nascent bronchial tips (PubMed:17920587). At 12.5 dpc, expressed in the optic vesicle, detected mainly in the retinal layer (PubMed:17920587). The retinal pigment epithelium shows only background levels (PubMed:17920587). At 15.5 dpc expressed at the basolateral side of the plasma membrane in brain, spinal cord, kidney, testis, intestine, skin, and muscles (PubMed:17920587).|||Cell membrane|||Component of a complex composed of PALS1, CRB1 and EPB41L5 (By similarity). Within the complex, interacts (via FERM domain) with PALS1 (via HOOK domain) and with CRB1 (via intracellular domain) (By similarity). Interacts with CRB2 (via intracellular domain) (By similarity). Interacts with CRB3 (via intracellular domain) (By similarity).|||Cytoplasm|||In the retina, expressed at the outer limiting membrane, retinal pigment epithelium, outer nuclear layer and outer plexiform layer (at protein level) (PubMed:17920587). Also detected in the inner segments (at protein level) (PubMed:17920587). Expressed at the basolateral and apical sides of the mesonephric tubules in the kidney (at protein level) (PubMed:17920587).|||Photoreceptor inner segment|||Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells.|||adherens junction http://togogenome.org/gene/10090:Deup1 ^@ http://purl.uniprot.org/uniprot/Q7M6Y5|||http://purl.uniprot.org/uniprot/U5KUF9 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CEP63 family.|||CEP63 and DEUP1 paralogs are both involved in centriole amplification: while CEP63 mediates mother-centriole-dependent centriole duplication, DEUP1 mediates de novo centriole amplification in multiciliated cells.|||Cytoplasm|||Highly enriched in multicilia-abundant tissues (trachea and oviduct).|||Interacts with CEP152; the interaction is mutually exclusive with CEP63.|||It is uncertain whether Met-1 or Met-22 is the initiator.|||Key structural component of the deuterosome, a structure that promotes de novo centriole amplification in multiciliated cells. Deuterosome-mediated centriole amplification occurs in terminally differentiated multiciliated cells and can generate more than 100 centrioles. Probably sufficient for the specification and formation of the deuterosome inner core. Interacts with CEP152 and recruits PLK4 to activate centriole biogenesis. http://togogenome.org/gene/10090:Arsa ^@ http://purl.uniprot.org/uniprot/P50428 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Endoplasmic reticulum|||Homodimer at neutral pH and homooctamer at acidic pH. Exists both as a single chain of 58 kDa (component A) or as a chain of 50 kDa (component B) linked by disulfide bond(s) to a 7 kDa chain (component C). Interacts with SUMF1 (By similarity).|||Hydrolyzes cerebroside sulfate.|||Lysosome|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. This post-translational modification is severely defective in multiple sulfatase deficiency (MSD). http://togogenome.org/gene/10090:Pkib ^@ http://purl.uniprot.org/uniprot/F7D7A9|||http://purl.uniprot.org/uniprot/Q3TZU5|||http://purl.uniprot.org/uniprot/Q6P8N5|||http://purl.uniprot.org/uniprot/Q8BNE5 ^@ Function|||Similarity ^@ Belongs to the PKI family.|||Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains. http://togogenome.org/gene/10090:Sh3rf2 ^@ http://purl.uniprot.org/uniprot/Q8BZT2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated.|||Belongs to the SH3RF family.|||Has E3 ubiquitin-protein ligase activity. Acts as an anti-apoptotic regulator of the JNK pathway by ubiquitinating and promoting the degradation of SH3RF1, a scaffold protein that is required for pro-apoptotic JNK activation. Facilitates TNF-alpha-mediated recruitment of adapter proteins TRADD and RIPK1 to TNFRSF1A and regulates PAK4 protein stability via inhibition of its ubiquitin-mediated proteasomal degradation. Inhibits PPP1CA phosphatase activity (By similarity).|||Interacts with FASLG and PPP1CA. Interacts with PAK4 and TNFRSF1A. Interacts with DLK1, MAP3K10, MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3. Interacts with RAC1 (both active GTP- or inactive GDP-bound forms).|||Nucleus|||The RING finger domain is required for ubiquitin ligase activity and autoubiquitination. http://togogenome.org/gene/10090:Acsbg1 ^@ http://purl.uniprot.org/uniprot/Q99PU5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family. Bubblegum subfamily.|||Catalyzes the conversion of fatty acids such as long-chain and very long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (By similarity) (PubMed:11112418, PubMed:12975357, PubMed:14516277). Can activate diverse saturated, monosaturated and polyunsaturated fatty acids (PubMed:11112418, PubMed:14516277).|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Endoplasmic reticulum|||First detected on embryonic day 18 and increases steadily towards adulthood.|||Mainly expressed in brain. Also expressed in adrenal gland and testis. In brain, it is present in cerebral cortical and cerebellar neurons and in steroidogenic cells of the adrenal gland, testis and ovary (at protein level).|||Microsome http://togogenome.org/gene/10090:Eif2s1 ^@ http://purl.uniprot.org/uniprot/Q6ZWX6 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (43S PIC) (PubMed:11106749, PubMed:12176355, PubMed:15277680, PubMed:19131336, PubMed:21285359). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR, such as ATF4, ATF5, DDIT3/CHOP and PPP1R15A/GADD34 (PubMed:15277680, PubMed:19131336, PubMed:21285359).|||Belongs to the eIF-2-alpha family.|||Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:15277680, PubMed:19131336). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex (PubMed:15277680, PubMed:19131336). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex (PubMed:15277680, PubMed:19131336). In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (PubMed:15277680, PubMed:19131336). EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases (EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2) in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:15277680, PubMed:21285359).|||Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs (PubMed:10504407, PubMed:11106749, PubMed:12176355, PubMed:15213227, PubMed:15277680, PubMed:16054071, PubMed:19131336, PubMed:21285359). Substrate for at least 4 kinases: EIF2AK1/HRI, EIF2AK2/PKR, EIF2AK3/PERK and EIF2AK4/GCN2 (PubMed:10504407, PubMed:11106749, PubMed:12176355, PubMed:15213227, PubMed:15277680, PubMed:16054071). Phosphorylated; phosphorylation on Ser-52 by the EIF2AK4/GCN2 protein kinase occurs in response to amino acid starvation and UV irradiation (PubMed:10504407, PubMed:12176355, PubMed:15213227, PubMed:16054071).|||Stress granule|||This gene should not be confused with EIF2A, with which it shares the alias EIF2A. Although both of these proteins function in binding initiator tRNA to the 40S ribosomal subunit, the eIF2 complex requires GTP, whereas the EIF2A protein does so in a codon-dependent manner.|||eIF2 is an heterotrimer composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (EIF2S3) chain (By similarity). eIF2 is member of the 43S pre-initiation complex (43S PIC). eIF2 forms a complex with at least CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (PubMed:16931514). Interaction with METAP2 protects EIF2S1 from inhibitory phosphorylation (By similarity). Interacts with ABCF1 (By similarity). Associates with ribosomes (By similarity). Interacts with DDX3X in an RNA-independent manner (By similarity). http://togogenome.org/gene/10090:Coro6 ^@ http://purl.uniprot.org/uniprot/B9EIZ7 ^@ Similarity ^@ Belongs to the WD repeat coronin family. http://togogenome.org/gene/10090:Camta1 ^@ http://purl.uniprot.org/uniprot/A2A891 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAMTA family.|||Cytoplasm|||May interact with calmodulin.|||Nucleus|||Transcriptional activator. http://togogenome.org/gene/10090:Tgif2 ^@ http://purl.uniprot.org/uniprot/A2AVY9|||http://purl.uniprot.org/uniprot/Q3TZS1|||http://purl.uniprot.org/uniprot/Q8C0Y1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TALE/TGIF homeobox family.|||Interacts with the transcriptional modulator SMAD3 and the histone deacetylase HDAC1.|||Nucleus|||The C-terminal part is phosphorylated in response to EGF signaling by the Ras/MAPK pathway.|||Transcriptional repressor, which probably repress transcription by binding directly the 5'-CTGTCAA-3' DNA sequence or by interacting with TGF-beta activated SMAD proteins. Probably represses transcription via the recruitment of histone deacetylase proteins (By similarity). http://togogenome.org/gene/10090:Enpep ^@ http://purl.uniprot.org/uniprot/P16406|||http://purl.uniprot.org/uniprot/Q52JJ6|||http://purl.uniprot.org/uniprot/Q6P3C1|||http://purl.uniprot.org/uniprot/Q8CD51 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Early B-lineage cells and certain stromal cell of hemopoietic tissues. Also expressed by capillary endothelial cells, placenta, and epithelial cells of the intestine and proximal renal tubules.|||Homodimer; disulfide-linked.|||Regulates central hypertension through its calcium-modulated preference to cleave N-terminal acidic residues from peptides such as angiotensin II.|||Substrate specificity is modulated by calcium which enhances the enzymatic activity for cleavage of acidic residues while reducing its activity with basic residues. Inhibited by aminopeptidase inhibitors amastatin and bestatin. http://togogenome.org/gene/10090:Apobec3 ^@ http://purl.uniprot.org/uniprot/Q99J72 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytidine and deoxycytidylate deaminase family.|||Cytoplasm|||DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity against HIV-1, simian immunodeficiency viruses (SIVs), mouse mammary tumor virus (MMTV) and friend murine leukemia virus (FrMLV) and may inhibit the mobility of LTR retrotransposons.|||Expressed in spleen, node and lung.|||Homodimer. Interacts with mouse mammary tumor virus (MMTV) nucleocapsid protein p14.|||Lacks exon V. Found in cell line MDTF.|||Probable human APOBEC3G ortholog.|||The CMP/dCMP deaminase domain 1 confers deoxycytidine deaminase activity, whereas the CMP/dCMP deaminase domain 2 mediates RNA-dependent oligomerization and virion incorporation. http://togogenome.org/gene/10090:Smco1 ^@ http://purl.uniprot.org/uniprot/Q8CEZ1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Sema3a ^@ http://purl.uniprot.org/uniprot/A0A803Z7F8|||http://purl.uniprot.org/uniprot/O08665 ^@ Caution|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the semaphorin family.|||Expressed early in embryonic development (11 dpc) in distinct regions of the neuroectoderm and mesoderm. Expression became more extensive at later stages.|||Interacts with PXND1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Plays a role in growth cones guidance. May function to pattern sensory projections by selectively repelling axons that normally terminate dorsally. Involved in the development of the olfactory system and in neuronal control of puberty (By similarity).|||Secreted|||Strong binding to neuropilin is mediated by the carboxy third of the protein. http://togogenome.org/gene/10090:Cstpp1 ^@ http://purl.uniprot.org/uniprot/Q8BHR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CSTPP1 family.|||Interacts with PCM1. Interacts with TTLL1, TPGS1, TPGS2 and LRRC49; the interactions link CSTPP1 to the complex TPGC. Binds to alpha-tubulin.|||Regulator of the tubulin polyglutamylase complex (TPGC) that controls cytoskeletal organization, nuclear shape, and cilium disassembly by balancing microtubule and actin assembly. Regulates the assembly and stability of the TPGC and thereby modulates polyglutamylation of the microtubule, which antagonizes MAP4 binding.|||centriolar satellite|||cytoskeleton http://togogenome.org/gene/10090:Fip1l1 ^@ http://purl.uniprot.org/uniprot/Q9D824 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FIP1 family.|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex (By similarity).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with CPSF1, CPSF4, CSTF2 and CSTF3 (By similarity). Interacts with AHCYL1 (when phosphorylated); the interaction is direct and associates AHCYL1 with the CPSF complex and RNA (PubMed:19224921). Interacts with PAPOLA; the interaction seems to be increased by the interaction with AHCYL1 (PubMed:19224921). Interacts with NUDT21/CPSF5; this interaction occurs in a RNA sequence-specific manner. Interacts (preferentially via unphosphorylated form and Arg/Glu/Asp-rich domain) with CPSF6 (via Arg/Ser-rich domain); this interaction mediates, at least in part, the interaction between the CFIm and CPSF complexes and may be inhibited by CPSF6 hyper-phosphorylation. Interacts (preferentially via unphosphorylated form and Arg/Asp/Glu-rich domain) with CPSF7 (via Arg/Ser-rich domain); this interaction mediates, at least in part, the interaction between the CFIm and CPSF complexes and may be inhibited by CPSF7 hyper-phosphorylation (By similarity).|||Nucleus http://togogenome.org/gene/10090:Arnt2 ^@ http://purl.uniprot.org/uniprot/Q61324 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein (By similarity). Heterodimer with NPAS4 or SIM1 (PubMed:27782878). Heterodimer with the aryl hydrocarbon receptor (AHR) or the SIM1 protein (By similarity). Interacts with TACC3 (PubMed:11025203).|||Nucleus|||Restricted to adult brain and kidney.|||Transcription factor that plays a role in the development of the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function. Specifically recognizes the xenobiotic response element (XRE). http://togogenome.org/gene/10090:Magohb ^@ http://purl.uniprot.org/uniprot/A0A023T778|||http://purl.uniprot.org/uniprot/G3UZW7|||http://purl.uniprot.org/uniprot/Q9CQL1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mago nashi family.|||Component of the pre-catalytic, catalytic and post-catalytic spliceosome complexes. Heterodimer with RBM8A. Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A.|||In macrophages, strongly induced by bacterial lipopolysaccharide (LPS). Levels reach a maximum 6 hours after exposure to LPS and are lower, but still much increased after 12 and 24 hours.|||Nucleus|||Required for pre-mRNA splicing as component of the spliceosome. Plays a redundant role with MAGOH in the exon junction complex and in the nonsense-mediated decay (NMD) pathway.|||Ubiquitous. Detected in brain, heart, liver, lung, spleen and testis. http://togogenome.org/gene/10090:Tsen54 ^@ http://purl.uniprot.org/uniprot/Q8C2A2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEN54 family.|||Non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5' and 3' splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3' cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events (By similarity).|||Nucleus|||nucleolus|||tRNA splicing endonuclease is a heterotetramer composed of TSEN2, TSEN15, TSEN34/LENG5 and TSEN54. tRNA splicing endonuclease complex also contains proteins of the pre-mRNA 3'-end processing machinery such as CLP1, CPSF1, CPSF4 and CSTF2 (By similarity). http://togogenome.org/gene/10090:Egr1 ^@ http://purl.uniprot.org/uniprot/P08046|||http://purl.uniprot.org/uniprot/Q544D6|||http://purl.uniprot.org/uniprot/Q8CAT6 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the EGR C2H2-type zinc-finger protein family.|||Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers (PubMed:1740423, PubMed:8336701, PubMed:2028256, PubMed:8939742). The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif (PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine (By similarity).|||By growth factors (PubMed:3133658). Up-regulated in lung vasculature in response to reperfusion after ischemia (PubMed:11100120). Up-regulated in liver in response to partial hepatectomy (PubMed:15265859).|||Cytoplasm|||Detected in lung vasculature and in mononuclear phagocytes (PubMed:11100120). Detected in liver (at protein level) (PubMed:15265859). Detected in lung vasculature and in mononuclear phagocytes (PubMed:11100120). Expressed in the liver in a circadian manner (PubMed:26471974).|||Interacts with SNAI1 and SP1 upon 12-O-tetradecanoylphorbol-13-acetate (TPA) induction.|||Mice appear grossly normal, but females are anestrous and infertile with an uterus weight that is roughly 30% of that of wild-type. Ovaries contain normal numbers of follicles, but lack corpora lutea. Serum progesterone levels are strongly reduced; estradiol levels are normal. The level of luteinizing hormone (LHB) in the pituitary is strongly reduced in males and not detectable in females (PubMed:8703054). Responses to ischemia and hypoxia are blunted, leading to reduced tissue damage in response to ischemia and increased survival (PubMed:11100120). Liver regeneration is impaired after partial hepatectomy, due to impaired mitotic progress and reduced proliferation of hepatocytes (PubMed:15265859). Untreated mutant mice do not display an increased tendency to develop tumors, but develop tumors earlier than wild-type when treated first with a tumor initiator, and then with a tumor promoter (PubMed:15958557). Mice lack daily rhythmicity in the expression of the core-clock gene BMAL1 and display a reduced and altered locomotor activity and altered temperature regulation (PubMed:29138967).|||Nucleus|||Transcriptional regulator (PubMed:8336701, PubMed:8703054, PubMed:15958557). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (PubMed:8703054, PubMed:15958557, PubMed:2028256, PubMed:8939742). Binds double-stranded target DNA, irrespective of the cytosine methylation status (By similarity). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia (PubMed:11100120, PubMed:15958557). Plays a role in the regulation of cell survival, proliferation and cell death (PubMed:15265859, PubMed:15958557). Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation (PubMed:15958557). Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy (PubMed:15265859). Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia (PubMed:11100120). Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (PubMed:8703054). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription (PubMed:26471974). Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (PubMed:29138967).|||Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. http://togogenome.org/gene/10090:Meis1 ^@ http://purl.uniprot.org/uniprot/Q60954 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator of PAX6. Also acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.|||Belongs to the TALE/MEIS homeobox family.|||Expressed at high levels in all stages of embryonic development analyzed (7 days to 17 days).|||Expressed at high levels in the lung with lower levels detected in the heart and brain. Expressed in pancreatic islets (beta-cells and non-beta-cells) (PubMed:21059917).|||Expression is coactivated by retroviral integration in BXH-2 murine myeloid leukemias.|||Interacts with the N-terminal region of PBX1 to form a heterodimer which binds DNA including a cAMP-responsive sequence in CYP17. Also forms heterodimers with PBX2. Forms heterotrimers with PBX1 or PBX2 and a number of HOX proteins including HOXA9, HOXD4 and HOXD9 where it acts as a non-DNA-binding partner. Also forms heterotrimers with PBX1 and HOX proteins including HOXD9 and HOXD10 where PBX1 is the non-DNA-binding partner. Heterodimer with DLX3. Heterodimer with HOXB13 (By similarity).|||Meis1 serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice that develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus.|||Mice die between embryonic days 11.5 and 14.5, showing internal hemorrhage, liver hypoplasia and anemia.|||Nucleus http://togogenome.org/gene/10090:Mndal ^@ http://purl.uniprot.org/uniprot/D0QMC3 ^@ Function|||Induction|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HIN-200 family.|||By interferon-alpha and interferon-beta.|||Highest expression observed in spleen and thymus with moderate levels in bone marrow, lung, skin and heart, low levels in muscle, liver and intestine and little or no expression in brain and pancreas.|||Nucleus|||Suppresses cell growth when expressed ectopically.|||This gene is present in strains 129/J, 129/SvJ, BALB/cAn, BALB/cJ, BALB/cHeA, CBA/N, C3H/HeJ, C3H/HeN, C57BL/6J, C57BL/10SnJ, C57L/J, NOD and NZW/LacJ but is absent in strains 129S6/SvEvTac, AKR/N, A/J, DBA/2J, NON, NZB/BlNJ, P/J, SENCARA/Pt, SWR/J and STS/A. http://togogenome.org/gene/10090:Sag ^@ http://purl.uniprot.org/uniprot/P20443|||http://purl.uniprot.org/uniprot/Q3UPX6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the arrestin family.|||Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO (PubMed:9333241, PubMed:16421323). May play a role in preventing light-dependent degeneration of retinal photoreceptor cells (PubMed:16421323).|||Detected in retina (at protein level).|||Membrane|||Monomer. Homodimer. Homotetramer (PubMed:21288033). Interacts with RHO (via the phosphorylated C-terminus) (PubMed:26200343, PubMed:28753425).|||The C-terminus interferes with binding to non-phosphorylated RHO. Interaction with phosphorylated RHO triggers displacement of the C-terminus and leads to a conformation change that mediates high-affinity RHO binding.|||The morphology of the retina is not affected when mice are kept in constant darkness. When mice are exposed to alternating 12 hour light and dark cycles, the rod photoreceptor outer segments are about 25% shorter than in wild-type, and the photoreceptor outer segments appear somewhat disordered (PubMed:9333241). After one year exposure to alternating 12 hour light and dark cycles, there are clear signs of photoreceptor degeneration with about 50% reduction in the number of photoreceptor nuclei in the outer layer of the retina (PubMed:16421323). Rod photoreceptor cells show normal flash sensitivity, but display prolonged RHO signaling, due to a strongly decreased rate of deactivation (PubMed:9333241, PubMed:16421323).|||photoreceptor outer segment http://togogenome.org/gene/10090:Klra7 ^@ http://purl.uniprot.org/uniprot/F8WJ94|||http://purl.uniprot.org/uniprot/Q60654 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked.|||Membrane|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Vmn2r55 ^@ http://purl.uniprot.org/uniprot/G3UWZ4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Fgf2 ^@ http://purl.uniprot.org/uniprot/P15655|||http://purl.uniprot.org/uniprot/Q541T2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Also acts as an integrin ligand which is required for FGF2 signaling (By similarity). Binds to integrin ITGAV:ITGB3 (By similarity). Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration (By similarity). Functions as a potent mitogen in vitro (By similarity). Can induce angiogenesis (By similarity). Mediates phosphorylation of ERK1/2 and thereby promotes retinal lens fiber differentiation (By similarity).|||Belongs to the heparin-binding growth factors family.|||Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Interacts with CSPG4, FGFBP1 and TEC. Found in a complex with FGFBP1, FGF1 and FGF2 (By similarity). Interacts with FGFBP3 (PubMed:20851768). Interacts with integrin ITGAV:ITGB3; the interaction is required for FGF2 signaling (By similarity). Interacts with SNORC (via the extracellular domain) (PubMed:28323137). Interacts with glypican GPC3 (By similarity).|||Nucleus|||Phosphorylation at Tyr-81 regulates FGF2 unconventional secretion.|||Secreted http://togogenome.org/gene/10090:Kdm4c ^@ http://purl.uniprot.org/uniprot/A2BEG5|||http://purl.uniprot.org/uniprot/Q8VCD7 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the JHDM3 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.|||Nucleus|||The 2 Tudor domains recognize and bind methylated histones. Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails (By similarity). http://togogenome.org/gene/10090:Terb2 ^@ http://purl.uniprot.org/uniprot/Q9D494 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TERB2 family.|||Component of the MAJIN-TERB1-TERB2 complex, composed of MAJIN, TERB1 and TERB2.|||Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA.|||Mice develop normally, exhibit no overt phenotype, but are infertile (both males and females). Gonads are characterized by the absence of post-meiotic cells.|||Nucleus inner membrane|||Specifically expressed in germline tissues.|||telomere http://togogenome.org/gene/10090:Pcgf6 ^@ http://purl.uniprot.org/uniprot/Q99NA9 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of a PRC1-like complex. Interacts with BMI1/PCGF4, RING1 and RNF2. Interacts with KDM5D. Interacts with CBX4, CBX6, CBX7 and CBX8.|||Expressed in embryo at 10.5 dpc.|||Expressed in ovary, testis, stomach, liver, thymus and kidney (at protein level).|||Nucleus|||Phosphorylated during mitosis.|||Transcriptional repressor. May modulate the levels of histone H3K4Me3 by activating KDM5D histone demethylase. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity. http://togogenome.org/gene/10090:Tapt1 ^@ http://purl.uniprot.org/uniprot/Q4VBD2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TAPT1 family.|||Membrane|||Mice die during perinatal development and are the cause of the L5Jcs1 phenotype. They exhibit posterior-to-anterior transformations of the vertebral column midsection, similar to mice deficient for Hoxc8 and Hoxc9.|||Plays a role in primary cilia formation (By similarity). May act as a downstream effector of HOXC8 possibly by transducing or transmitting extracellular information required for axial skeletal patterning during development (By similarity). May be involved in cartilage and bone development (By similarity). May play a role in the differentiation of cranial neural crest cells (By similarity).|||Ubiquitous. Expressed throughout embryo.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Mcpt2 ^@ http://purl.uniprot.org/uniprot/P15119 ^@ Similarity|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Mucosal mast cells. http://togogenome.org/gene/10090:Wnt9a ^@ http://purl.uniprot.org/uniprot/Q8R5M2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Wnt family.|||Expressed in adult brain, lung, skeletal muscle, heart, and 17-day embryo.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids.|||Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway (By similarity). Required for normal timing of IHH expression during embryonic bone development, normal chondrocyte maturation and for normal bone mineralization during embryonic bone development (PubMed:16818445). Plays a redundant role in maintaining joint integrity (PubMed:16818445).|||Mutant mice die during the first 12 hours after birth. Heart, lung, liver, intestinal tract, kidney and brain appear grossly normal, but the mice display skeletal abnormalities, with slightly shortened long bones in their limbs. The region of bone mineralization is reduced in scapula, humerus, ileum and femur. Besides, hyoid bone and atlas are hypoplastic. In the scull, the supraoccipital bone shows reduced mineralization, with increased distance between the frontal bones. The basioccipital bone displays an abnormal shape and is smaller than in wild-type. Ectopic cartilage nodules are detected within the skull midline sutures. Ectopic cartilaginous material is detected in the interfrontal and sagittal suture regions between the frontal and parietal bones. In neonate forelimbs, the synovial fold contains cells with a chondrocyte-like appearance. Mutant mice display also partial joint fusions between the navicular and intermediate cuneiform tarsal elements in the foot, and between wrist carpal elements.|||Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Gucy2g ^@ http://purl.uniprot.org/uniprot/Q6TL19 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Cell membrane|||Highly expressed in testis.|||Homooligomer. In vitro interacts with NPR1/GC-A.|||N-glycosylated. http://togogenome.org/gene/10090:Tnfsf4 ^@ http://purl.uniprot.org/uniprot/B6DXE3|||http://purl.uniprot.org/uniprot/P43488 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.|||Homotrimer.|||Membrane http://togogenome.org/gene/10090:Sox4 ^@ http://purl.uniprot.org/uniprot/Q06831 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-95 by KAT5 promotes the transcription activator activity and is required during myoblast differentiation (By similarity). Acetylation by KAT5 abolishes the interaction between SOX4 and HDAC1 and switches SOX4 into a transcriptional activator (By similarity).|||Expressed in both gamma-delta T-cells and Cd4+ Cd8+ double-positive (DP) alpha-beta T-cells (PubMed:17218525). Expressed in the ovaries and the thymus (PubMed:8404853, PubMed:17218525).|||Expressed in molar and incisor tooth germs at 14.5 dpc.|||In T-cell-specific knockout mice, loss of mature Il17a-producing Vgamma2-positive gamma-delta T-cells and reduction of Rorc expression in immature Vgamma2-positive thymocytes (PubMed:23562159). In a mouse model for psoriasis, dermal inflammation induced by skin application of TLR7 synthetic ligand imiquimod is substantially reduced due to the absence of Vgamma2-positive gamma-delta T-cells (PubMed:23562159).|||Interacts with UBE2I. Interacts with HDAC1; interaction inhibits the transcriptional activator activity.|||May be involved in the T-cell immune response in the psoriasis-like disease which is induced in mice by the application of the TLR7 ligand Imiquimod to skin.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif (PubMed:8404853). Required for IL17A-producing Vgamma2-positive gamma-delta T-cell maturation and development, via binding to regulator loci of RORC to modulate expression (PubMed:23562159). Involved in skeletal myoblast differentiation by promoting gene expression of CALD1 (PubMed:26291311). http://togogenome.org/gene/10090:Gpr179 ^@ http://purl.uniprot.org/uniprot/E9PY61 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Defects in Gpr179 are the cause of nob5 (no b-wave 5), a spontaneous mutation that causes failure to transmit the photoreceptor signal through the depolarizing bipolar cells, characterized by an absence of the electroretinogram (ERG) b-wave (PubMed:22325362, PubMed:24415894, PubMed:24084093). In retina, rod and cone ON-bipolar cell function is absent (PubMed:22325362).|||Defects in Pde6b are involved in the retinal degeneration 1 (rd1) allele, which causes retinal degeneration (PubMed:25613321). The rd1 allele is mainly caused by defects in the Pde6b gene, but it contains a cofounding mutation in the Gpr179 gene (PubMed:25613321).|||Homodimer (PubMed:34333057). Associates with the R7 group RGS-GNB5 complexes, composed of an R7 group RGS subunit (RGS6, RGS7, RGS9 or RGS11) and GNB5, promoting their localization to the cell membrane and regulating the GTPase activator activity of R7 RGS proteins (PubMed:22689652). Interacts with TRPM1 (PubMed:24114537, PubMed:24790204). Interacts with GRM6 (PubMed:24114537). Interacts with EGFLAM; transsynaptic interaction is required for synaptic organization of photoreceptor cells (PubMed:30282023).|||Mice display impaired night vision due to a failure to transmit the photoreceptor signal through the depolarizing bipolar cells (PubMed:33922602). Mice also show myopic features, probably caused by a decrease in both retinal dopamine and 3,4-dihydroxyphenylacetic acid (PubMed:36613663).|||Orphan receptor involved in vision (PubMed:22325362, PubMed:24114537, PubMed:24790204, PubMed:30282023). Required for signal transduction through retinal depolarizing bipolar cells (PubMed:22325362, PubMed:24114537, PubMed:24790204, PubMed:33922602). Acts as an atypical G-protein coupled receptor that recruits and regulates the R7 group RGS-GNB5 complexes instead of activating G proteins: promotes the GTPase activator activity of R7 RGS proteins, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:22689652, PubMed:24790204). Associates with components of metabotropic signaling cascade in retina ON-bipolar neurons, such as TRPM1 and GRM6: may control the ability of the GRM6 cascade to gate TRPM1 (PubMed:24114537, PubMed:24790204).|||Postsynaptic cell membrane|||dendrite http://togogenome.org/gene/10090:Memo1 ^@ http://purl.uniprot.org/uniprot/Q91VH6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the MEMO1 family.|||Interacts with ERBB2 phosphorylated on 'Tyr-1249'.|||May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. Mediator of ERBB2 signaling. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). http://togogenome.org/gene/10090:Tmem225 ^@ http://purl.uniprot.org/uniprot/Q9D9S2 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in testis 25 days after birth and thereafter.|||Expressed in testis, epididymis and spermatozoa (at protein level). Not expressed in brain, heart, lung, liver, spleen, kidney and skeletal muscle.|||Interacts (via RVxF motif) with PPP1CC.|||Probably inhibits protein phosphatase 1 (PP1) in sperm via binding to catalytic subunit PPP1CC.|||This protein is not related to the claudin family.|||acrosome membrane http://togogenome.org/gene/10090:Spata31d1d ^@ http://purl.uniprot.org/uniprot/E9Q5W2|||http://purl.uniprot.org/uniprot/Q8C5W2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Eef1g ^@ http://purl.uniprot.org/uniprot/Q4FZK2|||http://purl.uniprot.org/uniprot/Q9D8N0 ^@ Function|||Subunit ^@ EF-1 is composed of four subunits: alpha, beta, delta, and gamma.|||Probably plays a role in anchoring the complex to other cellular components. http://togogenome.org/gene/10090:Fzr1 ^@ http://purl.uniprot.org/uniprot/Q3U3D4|||http://purl.uniprot.org/uniprot/Q9R1K5 ^@ Function|||PTM|||Similarity|||Subunit ^@ Acetylated. Deacetylated by SIRT2 at Lys-69 and Lys-159; deacetylation enhances the interaction of FZR1 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C).|||Belongs to the WD repeat CDC20/Fizzy family.|||Following DNA damage, it is dephosphorylated by CDC14B in G2 phase, leading to its reassociation with the APC/C, and allowing an efficient G2 DNA damage checkpoint (By similarity). Phosphorylated by MAK (By similarity).|||Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR).|||The unphosphorylated form interacts with APC/C during mitosis. Interacts with NINL. Interacts (in complex with the anaphase promoting complex APC) with MAD2L2; inhibits FZR1-mediated APC/C activation (By similarity). Interacts with SIRT2 (PubMed:22014574). Interacts with USP37. Interacts (via WD repeats) with MAK. Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation. Interacts with HECW2 (By similarity). Interacts with SASS6; the interaction is regulated by CENATAC and leads to SASS6 proteasomal degradation (By similarity). Interacts (via N-terminus) with CCNF (By similarity). Interacts with CDC6 (By similarity). Interacts with TK1 (via the KEN box) (By similarity). http://togogenome.org/gene/10090:Ydjc ^@ http://purl.uniprot.org/uniprot/Q14BV6 ^@ Function|||Similarity ^@ Belongs to the YdjC deacetylase family.|||Probably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides. http://togogenome.org/gene/10090:Colec10 ^@ http://purl.uniprot.org/uniprot/Q8CF98 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 16 dpc expressed in the liver, amnion and visceral yolk sac. Expression is gradually increased with embryonic age (PubMed:12450124). Expressed in the epithelium and mesenchyme of the palate shelf and jaw as early as 13.5 dpc. This particular mandibular epithelial expression is still present at 18.5 dpc (PubMed:28301481).|||Belongs to the COLEC10/COLEC11 family.|||Cytoplasm|||Expressed mainly in the liver and stomach, but also in muscles, testes, and intestines.|||Golgi apparatus|||Lectin that binds to various sugars: galactose > mannose = fucose > N-acetylglucosamine > N-acetylgalactosamine. Acts as a chemoattractant, probably involved in the regulation of cell migration.|||Secreted http://togogenome.org/gene/10090:Phc1 ^@ http://purl.uniprot.org/uniprot/Q3TJ47|||http://purl.uniprot.org/uniprot/Q3V116|||http://purl.uniprot.org/uniprot/Q64028 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By retinoic acid.|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Required for proper control of cellular levels of GMNN expression (By similarity).|||Expressed ubiquitously in 8.5 dpc embryos. At 10.5 dpc, strongly expressed in pharyngeal arches and weakly expressed in heart. By 14.5 dpc, expression is detected throughout the central nervous system.|||Highly expressed in testis with lower levels in most other tissues. Expressed in embryonic stem cells (PubMed:22226355).|||Homodimer. Component of a PRC1-like complex (By similarity). Interacts with the SAM domain of SCMH1 via its SAM domain in vitro (PubMed:10653359). Interacts with RNF2 and CBX7 (PubMed:22226355). Interacts with PHC2 (PubMed:16024804). Interacts with BMI1 (PubMed:9009205).|||Nucleus http://togogenome.org/gene/10090:Mettl5 ^@ http://purl.uniprot.org/uniprot/Q8K1A0 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily. PrmA family.|||Catalytic subunit of a heterodimer with TRMT112, which specifically methylates the 6th position of adenine in position 1832 of 18S rRNA (PubMed:32783360, PubMed:35033535). N6-methylation of adenine(1832) in 18S rRNA resides in the decoding center of 18S rRNA and is required for translation and embryonic stem cells (ESCs) pluripotency and differentiation (PubMed:32783360, PubMed:32217665).|||Heterodimer; heterodimerizes with TRMT112.|||Mice were born at non-Mendelian rates and develop morphological, such as craniofacial abnormalities, snout deviation due to altered nasal bone development and incomplete fusion of the frontal bone suture (PubMed:32217665). Mice display reduced body size and evidence of metabolic defects (PubMed:35033535). Mice also show behavioral abnormalities (PubMed:32217665). Deletion in embryonic stem cells (ESCs) results in a decrease in global translation rate, spontaneous loss of pluripotency and compromised differentiation potential (PubMed:32783360, PubMed:32217665). Cells show abolished level of N6-methylation of adenine(1832) in 18S rRNA (PubMed:35033535).|||Nucleus|||Postsynapse|||Presynapse|||Ubiquitously expressed in brain.|||rRNA N6-adenosine-methyltransferase activity is inhibited by zinc. http://togogenome.org/gene/10090:Dpy19l2 ^@ http://purl.uniprot.org/uniprot/P0CW70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dpy-19 family.|||Deficient male exhibit sterility associated with globozoospermia.|||Interacts with FAM209.|||Nucleus inner membrane|||Predominantly expressed in testis. Present in testis but absent from epididymal sperm (at protein level).|||Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.|||Required during spermatogenesis for sperm head elongation and acrosome formation. Also plays a role in acrosome attachment to the nuclear envelope. http://togogenome.org/gene/10090:Trmt12 ^@ http://purl.uniprot.org/uniprot/Q8BG71 ^@ Function|||Similarity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.|||S-adenosyl-L-methionine-dependent transferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the transfer of the alpha-amino-alpha-carboxypropyl (acp) group from S-adenosyl-L-methionine to the C-7 position of 4-demethylwyosine (imG-14) to produce wybutosine-86 (By similarity). http://togogenome.org/gene/10090:Wnk3 ^@ http://purl.uniprot.org/uniprot/Q80XP9 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated in response to hyperosmotic stress: cell shrinkage promotes formation of a membraneless compartment that concentrates WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK (By similarity). Activation requires autophosphorylation of Ser-307 and, to a lower extent, Ser-303 (By similarity). Autophosphorylation and subsequent activation is inhibited by increases in intracellular ionic strength: Cl(-) potently inhibits WNK3 kinase activity via direct binding (By similarity). Also inhibited by K(+) ions. Kinase activity is inhibited by WNK4 (By similarity).|||Autophosphorylated at Ser-303 and Ser-307, promoting its activity (By similarity). Phosphorylation at Thr-540 prevents interaction with KLHL3 and subsequent ubiquitination and degradation by the BCR(KLHL3) complex (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily.|||Cytoplasm|||Disordered regions undergo liquid-liquid phase separation (LLPS) for the formation of a cytoplasmic membraneless compartment that concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK.|||Expressed in pancreatic duct (PubMed:21317537).|||Interacts with WNK1 and WNK4.|||Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (By similarity). WNK3 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (By similarity). The membraneless compartment concentrates WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:19470686). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (By similarity). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (By similarity). May also phosphorylate NEDD4L (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (By similarity). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (By similarity).|||Ubiquitinated by the BCR(KLHL2) complex, leading to its degradation. Ubiquitinated by the BCR(KLHL3) complex, leading to its degradation.|||Was named WNK/'with no lysine(K)' because key residues for catalysis, including the lysine involved in ATP binding, are either not conserved or differ compared to the residues described in other kinase family proteins. http://togogenome.org/gene/10090:Lama5 ^@ http://purl.uniprot.org/uniprot/Q3TZ05|||http://purl.uniprot.org/uniprot/Q61001 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Alpha-5 may be the major laminin alpha chain of adult epithelial and/or endothelial basal laminae. Plays a role in the regulation of skeletogenesis, through a mechanism that involves integrin-mediated signaling and PTK2B/PYK2 (By similarity).|||Domains VI, IV and G are globular.|||In adult, high levels in heart, lung, and kidney; lower in brain, muscle and testis; very low in liver, gut and skin. Expressed in many tissues in embryonic day 11.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-5 is a subunit of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523).|||The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.|||basement membrane http://togogenome.org/gene/10090:Usp29 ^@ http://purl.uniprot.org/uniprot/Q9ES63 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C19 family.|||Deubiquitinase involved in innate antiviral immunity by mediating 'Lys-48'-linked deubiquitination of CGAS, thereby promoting its stabilization.|||No visible phenotype in normal conditions.|||Predominantly expressed in brain and testis (PubMed:30919279). Highest expression levels in adult brain, especially in the cerebral cortex and hippocampus, and in the forebrain, face, and limb buds of midgestation mouse embryos (PubMed:10958632).|||perinuclear region http://togogenome.org/gene/10090:Lrrc55 ^@ http://purl.uniprot.org/uniprot/Q3UY51 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium (By similarity).|||Cell membrane|||Interacts with KCNMA1.|||The transmembrane domain is necessary for interaction with KCNMA1. http://togogenome.org/gene/10090:Syp ^@ http://purl.uniprot.org/uniprot/Q62277 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synaptophysin/synaptobrevin family.|||Homohexamer or homotetramer. Interacts with SRCIN1 (By similarity). Interacts with VAMP2; the interaction is inhibit by interaction of VAPM2 with SEPT8 (PubMed:19196426).|||Mice lackin both SYNGR1 and SYP show normal brain structure and composition, but impaired short-term and long-term synaptic plasticity.|||Phosphorylated by SRC.|||Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane (By similarity). Involved in the regulation of short-term and long-term synaptic plasticity.|||The calcium-binding activity is thought to be localized in the cytoplasmic tail of the protein.|||Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation.|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Tnn ^@ http://purl.uniprot.org/uniprot/Q80Z71 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tenascin family.|||Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1 (By similarity) (PubMed:14709716). Involved in neurite outgrowth and cell migration in hippocampal explants (PubMed:12812753). During endochondral bone formation, inhibits proliferation and differentiation of proteoblasts mediated by canonical WNT signaling (PubMed:17395156). In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (By similarity). Expressed in most mammary tumors, may facilitate tumorigenesis by supporting the migratory behavior of breast cancer cells (PubMed:15592496).|||Hardly detectable at embryonic day (E) 14, then increases until postnatal day 17 and remains detectable in the adult (PubMed:12812753). Expressed as early as 11.5 dpc in the maxillary process until 16.5 dpc when is expressed in the newly formed mandible. At 14.5 dpc is detected in smooth muscle cells of the stomach and intestine and at 15.5, in the periosteum of the ribs. At 16.5 dpc the expression is restricted to mandible, palate and teeth (PubMed:14709716). During endochondral bone formation, first expressed at 13.5 dpc in the perichondrium. At E 16.5, detected in perichondrium and periosteum (PubMed:17395156).|||Highest expression in kidney followed by spleen and brain. In brain, highest expression is found in hippocampus, cerebellum and olfactory bulb. Expressed in aortic valve, corneal limbus (PubMed:14709716). Expressed in ribs periosteum. During a fracture repair process, expression increases in cells of newly formed perichondrium/peristeum surrounding the cartalaginous callus (PubMed:14709716, PubMed:17395156).|||Homohexamer.|||extracellular matrix http://togogenome.org/gene/10090:Cmbl ^@ http://purl.uniprot.org/uniprot/Q8R1G2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the dienelactone hydrolase family.|||Cysteine hydrolase.|||cytosol http://togogenome.org/gene/10090:Cd163 ^@ http://purl.uniprot.org/uniprot/B7ZMW6|||http://purl.uniprot.org/uniprot/Q2VLH6 ^@ Caution|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A soluble form (sCD163) is produced by proteolytic shedding which can be induced by lipopolysaccharide, phorbol ester and Fc region of immunoglobulin gamma. This cleavage is dependent on protein kinase C and tyrosine kinases and can be blocked by protease inhibitors. The shedding is inhibited by the tissue inhibitor of metalloproteinase TIMP3, and thus probably induced by membrane-bound metalloproteinases ADAMs (By similarity).|||After shedding, the soluble form (sCD163) may play an anti-inflammatory role.|||Cell membrane|||Expressed in monocytes and mature macrophages such as Kupffer cells in the liver, red pulp macrophages in the spleen and mesenteric lymph nodes.|||Induced by anti-inflammatory mediators such as glucocorticoids and IL10; suppressed by IL4.|||Interacts with CSNK2B.|||Involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted|||The SRCR domain 3 mediates calcium-sensitive interaction with hemoglobin/haptoglobin complexes. http://togogenome.org/gene/10090:Or2y1e ^@ http://purl.uniprot.org/uniprot/Q8VFA4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Zw10 ^@ http://purl.uniprot.org/uniprot/O54692 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZW10 family.|||Cytoplasm|||Endoplasmic reticulum membrane|||Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex. Involved in regulation of membrane traffic between the Golgi and the endoplasmic reticulum (ER); the function is proposed to depend on its association in the interphase NRZ complex which is believed to play a role in SNARE assembly at the ER (By similarity).|||Interacts with NBAS and KNTC1/ROD; the interactions are mutually exclusive and indicative for its association in two different vesicle tethering complexes (By similarity). Component of the RZZ complex composed of KNTC1/ROD, ZW10 and ZWILCH (By similarity). Component of the NRZ complex composed of NBAS, ZW10 and RINT1/TIP20L; NRZ associates with SNAREs STX18, USE1L, BNIP1/SEC20L and SEC22B (the assembly has been described as syntaxin 18 complex) (By similarity). Interacts directly with RINT1/TIP20L bound to BNIP1/SEC20L (By similarity). Interacts with C19orf25 and ZWINT (By similarity). Interacts with ZFYVE1 (By similarity). Interacts with RAB18 and this interaction is enhanced in the presence of ZFYVE1 (By similarity).|||Lipid droplet|||kinetochore|||spindle http://togogenome.org/gene/10090:Sec14l4 ^@ http://purl.uniprot.org/uniprot/Q8R0F9 ^@ Function ^@ Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids. http://togogenome.org/gene/10090:Srgap2 ^@ http://purl.uniprot.org/uniprot/Q91Z67 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Expressed throughout cortical development culminating at P1. Expression is reduced but still present in the adult cortex. Expressed in the cortical wall both in neuronal progenitors in the ventricular zone and post-mitotic neurons in the cortical plate (at protein level).|||Homodimer (PubMed:19737524). Forms a heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain (By similarity). Interacts (via SH3 domain) with GPHN (PubMed:22126966, PubMed:27373832). Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1 and actin dynamics (PubMed:21148482). Interacts (via SH3 domain) with FMNL3 (PubMed:21148482). Interacts with RAC1; specifically stimulates RAC1 GTPase activity (PubMed:19737524). Interacts (via F-BAR domain) with HOMER1 (PubMed:27373832). Interacts with ROBO1 and ROBO2 (PubMed:21148482). Interacts with FASLG (By similarity). Interacts with PRMT5 (By similarity).|||Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions.|||Mice are viable and show no abnormality of cortical lamination. However, a delay in dendritic spine maturation coupled to an increase in spine neck and spine density is observed.|||Nucleus|||Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:19737524, PubMed:22559944, PubMed:27373832). Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:19737524, PubMed:22559944, PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (PubMed:27373832). Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:19737524, PubMed:22559944, PubMed:26439400). Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (PubMed:26439400). In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:22559944).|||Postsynaptic cell membrane|||Postsynaptic density|||The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.|||cytosol|||dendritic spine|||lamellipodium|||phagosome http://togogenome.org/gene/10090:Tm4sf19 ^@ http://purl.uniprot.org/uniprot/B2RWD4|||http://purl.uniprot.org/uniprot/E9Q9H8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the L6 tetraspanin family.|||Membrane http://togogenome.org/gene/10090:Cts3 ^@ http://purl.uniprot.org/uniprot/Q91ZD5|||http://purl.uniprot.org/uniprot/Q9DAZ8 ^@ Similarity ^@ Belongs to the peptidase C1 family. http://togogenome.org/gene/10090:Cxcr5 ^@ http://purl.uniprot.org/uniprot/Q04683 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC). Involved in B-cell migration into B-cell follicles of spleen and Peyer patches but not into those of mesenteric or peripheral lymph nodes.|||Mainly in spleen, in resting B-cells. http://togogenome.org/gene/10090:Ctps ^@ http://purl.uniprot.org/uniprot/P70698 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by GTP and inhibited by CTP.|||Belongs to the CTP synthase family.|||This enzyme is involved in the de novo synthesis of CTP, a precursor of DNA, RNA and phospholipids. Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as a source of nitrogen. This enzyme and its product, CTP, play a crucial role in the proliferation of activated lymphocytes and therefore in immunity.|||cytosol http://togogenome.org/gene/10090:Parm1 ^@ http://purl.uniprot.org/uniprot/Q923D3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PARM family.|||Cell membrane|||Endosome membrane|||Golgi apparatus membrane|||Highly N-glycosylated and O-glycosylated.|||May regulate TLP1 expression and telomerase activity, thus enabling certain prostatic cells to resist apoptosis. http://togogenome.org/gene/10090:Pmch ^@ http://purl.uniprot.org/uniprot/P56942 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MCH family.|||Expression is enhanced between postnatal days 10 and 15.|||MCH may act as a neurotransmitter or neuromodulator in a broad array of neuronal functions directed toward the regulation of goal-directed behavior, such as food intake, and general arousal.|||Predominantly expressed in hypothalamus. Also found in heart, intestine, spleen and testis (spermatogonia, early spermatocytes and Sertoli cells). In brain only mature MCH and NEI peptides are present. In peripheral tissues a large product, encompassing the NEI and MCH domains of the precursor, is found predominantly.|||Pro-MCH is processed differentially in the brain and in peripheral organs producing two neuropeptides; NEI and MCH. A third peptide, NGE, may also be produced. Preferential processing in neurons by prohormone convertase 2 (PC2) generates NEI. MCH is generated in neurons of the lateral hypothalmic area by several prohormone convertases including PC1/3, PC2 and PC5/6.|||Secreted http://togogenome.org/gene/10090:Iqcf1 ^@ http://purl.uniprot.org/uniprot/Q9D9K8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homozygote Iqcf1 mice are significantly less fertile because of reduced sperm motility and acrosome reaction.|||Interacts with calmodulin.|||Involved in sperm capacitation and acrosome reaction.|||Specifically expressed in testes and mature spermatozoa (at protein level).|||acrosome http://togogenome.org/gene/10090:Cpsf6 ^@ http://purl.uniprot.org/uniprot/H3BJ30|||http://purl.uniprot.org/uniprot/H3BJW3|||http://purl.uniprot.org/uniprot/Q6NVF9 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM CPSF6/7 family.|||Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. CPSF6 enhances NUDT21/CPSF5 binding to 5'-UGUA-3' elements localized upstream of pA signals and promotes RNA looping, and hence activates directly the mRNA 3'-processing machinery. Plays a role in mRNA export.|||Component of the cleavage factor Im (CFIm) complex which is a heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7. The cleavage factor Im (CFIm) complex associates with the CPSF and CSTF complexes to promote the assembly of the core mRNA 3'-processing machinery. Associates with the exon junction complex (EJC). Associates with the 80S ribosome particle. Interacts (via the RRM domain) with NUDT21/CPSF5; this interaction is direct and enhances binding to RNA. Interacts (via Arg/Ser-rich domain) with FIP1L1 (preferentially via unphosphorylated form and Arg/Glu/Asp-rich domain); this interaction mediates, at least in part, the interaction between the CFIm and CPSF complexes and may be inhibited by CPSF6 hyper-phosphorylation. Interacts (via N-terminus) with NXF1; this interaction is direct. Interacts with SRSF3. Interacts with SRSF7. Interacts with SNRNP70. Interacts with TRA2B/SFRS10. Interacts with UPF1. Interacts with UPF3B. Interacts with VIRMA. Interacts (via Arg/Ser-rich domain) with TNPO3; promoting nuclear import of CPSF6 independently of its phosphorylation status (By similarity). Interacts with YTHDC1 (PubMed:29799838).|||Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing and alternative polyadenylation (APA).|||Cytoplasm|||Expressed in testis (PubMed:18032416). Expressed in male germ cells (at protein level) (PubMed:18032416).|||Nucleus|||Nucleus speckle|||Phosphorylated. Phosphorylated in the Arg/Ser-rich domain by SRPK1, in vitro.|||Symmetrically dimethylated on arginine residues by PRMT5 in a WDR77- and CLNS1A-dependent manner. Asymmetrically dimethylated on arginine residues by PRMT1.|||Symmetrically dimethylated on arginine residues in the GAR motif by PRMT5 in a WDR77- and CLNS1A-dependent manner. Asymmetrically dimethylated on arginine residues in the GAR motif by PRMT1.|||Up-regulated during spermatogenesis (PubMed:18032416).|||nucleoplasm http://togogenome.org/gene/10090:Cacng1 ^@ http://purl.uniprot.org/uniprot/O70578|||http://purl.uniprot.org/uniprot/Q4KL26 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.|||Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:10799530, PubMed:12409298). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity).|||Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2.|||Detected in skeletal muscle (at protein level).|||Membrane|||N-glycosylated.|||No visible phenotype.|||Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics.|||sarcolemma http://togogenome.org/gene/10090:Zgpat ^@ http://purl.uniprot.org/uniprot/Q8VDM1 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Interacts with CHD4/Mi-2; the interaction is direct.|||Nucleus|||The sequence differs from that shown because it seems to be derived from a pre-mRNA.|||Transcription repressor that specifically binds the 5'-GGAG[GA]A[GA]A-3' consensus sequence. Represses transcription by recruiting the chromatin multiprotein complex NuRD to target promoters. Negatively regulates expression of EGFR, a gene involved in cell proliferation, survival and migration. Its ability to repress genes of the EGFR pathway suggest it may act as a tumor suppressor (By similarity). http://togogenome.org/gene/10090:Fgf23 ^@ http://purl.uniprot.org/uniprot/Q3U1V5|||http://purl.uniprot.org/uniprot/Q9EPC2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heparin-binding growth factors family.|||Following secretion this protein is inactivated by cleavage into a N-terminal fragment and a C-terminal fragment. The processing is effected by proprotein convertases (By similarity).|||Interacts with FGFR1 (PubMed:17086194). Interacts with FGFR2, FGFR3 and FGFR4 (By similarity). Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL and heparan sulfate glycosaminoglycans that function as coreceptors (PubMed:17086194).|||Mainly expressed in the brain and thymus at low levels. In brain; preferentially expressed in the ventrolateral thalamic nucleus.|||O-glycosylated at Thr-171 and Thr-178 by GALNT3 and glycosylation of Thr-178 requires previous glycosylation at Thr171. Glycosylation is necessary for secretion; it blocks processing by proprotein convertases when the O-glycan is alpha 2,6-sialylated. Competition between proprotein convertase cleavage and block of cleavage by O-glycosylation determines the level of secreted active FGF23 (By similarity).|||Phosphorylation at Ser-180 mediated by FAM20C slows down glycosylation at Thr-178 notably.|||Regulator of phosphate homeostasis (By similarity). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism (By similarity). Negatively regulates osteoblasts differentiation and matrix mineralization (By similarity). Up-regulates EGR1 expression in the presence of KL (PubMed:17086194).|||Secreted http://togogenome.org/gene/10090:Gng12 ^@ http://purl.uniprot.org/uniprot/Q9DAS9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Nop10 ^@ http://purl.uniprot.org/uniprot/Q9CQS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOP10 family.|||Cajal body|||Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. During assembly, the complex contains NAF1 instead of GAR1/NOLA1. The complex also interacts with TERC, which contains a 3'-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1.|||Required for ribosome biogenesis and telomere maintenance. Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. May also be required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (By similarity).|||nucleolus http://togogenome.org/gene/10090:Prkag3 ^@ http://purl.uniprot.org/uniprot/Q8BGM7 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. AMPK also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. The AMPK gamma3 subunit is a non-catalytic subunit with a regulatory role in muscle energy metabolism. It mediates binding to AMP, ADP and ATP, leading to AMPK activation or inhibition: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.|||AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity).|||Belongs to the 5'-AMP-activated protein kinase gamma subunit family.|||Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.|||The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.|||The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 (By similarity). http://togogenome.org/gene/10090:Apln ^@ http://purl.uniprot.org/uniprot/Q544B5|||http://purl.uniprot.org/uniprot/Q9R0R4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the apelin family.|||Endogenous ligand for the apelin receptor (APLNR). Drives internalization of APLNR (By similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (PubMed:10525157). Plays a role in early coronary blood vessels formation (PubMed:28890073). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (PubMed:11359874).|||Expressed in extraembryonic visceral endoderm and in the primitive streak at 6.5 and 7.5 dpc (PubMed:28854362). Expressed in the anterior visceral yolk sac at 8.25 dpc (PubMed:28854362). Expressed weakly in the embryonic heart at 11.5 dpc (PubMed:26611206). Expressed in the adult heart (PubMed:26611206). Expressed in endothelial cells and cardiomyocytes and weakly expressed in fibroblasts (PubMed:26611206).|||Mice heart of embryos show increased coronary vessel growth at 13.5 dpc and 15.5 dpc (PubMed:28890073). Double knockout mice of APELA and APLN genes exhibit the same penetrance, embryonic lethality and cardiovascular malformations as single APELA knockout mice (PubMed:28854362).|||Not up-regulated following myocardial infarction (MI) (at protein level) (PubMed:26611206).|||Secreted|||Several active peptides may be produced by proteolytic processing of the peptide precursor.|||extracellular space http://togogenome.org/gene/10090:Dusp4 ^@ http://purl.uniprot.org/uniprot/Q8BFV3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Hollow spherical complex composed of 24 subunits with pseudooctahedral symmetry, has a tetramer as the basic unit.|||Nucleus|||Phosphorylation in the C-terminus by ERK1/2 inhibits proteasomal degradation and stabilizes the protein.|||Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2. http://togogenome.org/gene/10090:Tle2 ^@ http://purl.uniprot.org/uniprot/Q3UN01|||http://purl.uniprot.org/uniprot/Q5DTI7|||http://purl.uniprot.org/uniprot/Q9WVB2 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat Groucho/TLE family.|||Expressed in bone marrow-derived macrophages.|||Homooligomer and heterooligomer with other family members (By similarity). Binds LEF1, TCF7, TCF7L1, TCF7L2, UTY, HES1 and HES5 (By similarity).|||Nucleus|||Repressed during TNFSF11/RANKL-induced osteoclast differentiation.|||Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity).|||Ubiquitinated by XIAP/BIRC4.|||WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain. http://togogenome.org/gene/10090:Or5b12 ^@ http://purl.uniprot.org/uniprot/Q8VFX1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Specc1l ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J8|||http://purl.uniprot.org/uniprot/Q2KN98|||http://purl.uniprot.org/uniprot/Q6GQV8|||http://purl.uniprot.org/uniprot/Q8C9Q9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 9.5-10.5 dpc, expressed in the developing maxillary prominence and the lateral nasal process, as well as in the limbs and eye.|||Belongs to the cytospin-A family.|||Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration (By similarity).|||Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration.|||May interact with both microtubules and actin cytoskeleton.|||cytoskeleton|||gap junction|||spindle http://togogenome.org/gene/10090:Flacc1 ^@ http://purl.uniprot.org/uniprot/Q8BVM7 ^@ Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic granule|||Isoform 1 is specific to germ cells of the testis and localizes to the principal piece of the sperm flagellum. Isoform 2 seems to be expressed mainly in somatic cells of the testis, and is not detected in mature spermatozoa (at protein level). Isoform 2 may also be expressed weakly in brain.|||May be due to intron retention.|||flagellum http://togogenome.org/gene/10090:Mrm3 ^@ http://purl.uniprot.org/uniprot/Q5ND52 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase TrmH family.|||Mitochondrion|||S-adenosyl-L-methionine-dependent 2'-O-ribose methyltransferase that catalyzes the formation of 2'-O-methylguanosine at position 1370 (Gm1370) in the 16S mitochondrial large subunit ribosomal RNA (mtLSU rRNA), a conserved modification in the peptidyl transferase domain of the mtLSU rRNA. http://togogenome.org/gene/10090:Teddm1b ^@ http://purl.uniprot.org/uniprot/Q8CC62 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Membrane http://togogenome.org/gene/10090:Dio3 ^@ http://purl.uniprot.org/uniprot/Q91ZI8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the iodothyronine deiodinase family.|||Cell membrane|||Endosome membrane|||Homodimer. May undergo minor heretodimerization with DIO1 and DIO2 (By similarity).|||It is uncertain whether Met-1 or Met-27 is the initiator.|||Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development. http://togogenome.org/gene/10090:Ccdc65 ^@ http://purl.uniprot.org/uniprot/Q8VHI7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DRC2 family.|||Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes. Coassembles with DRC1 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules.|||Component of the nexin-dynein regulatory complex (N-DRC). Interacts with DRC1.|||flagellum|||flagellum axoneme|||flagellum basal body http://togogenome.org/gene/10090:Eda2r ^@ http://purl.uniprot.org/uniprot/Q3KP88|||http://purl.uniprot.org/uniprot/Q8BX35 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Associates with TRAF1, TRAF3 and TRAF6.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for EDA isoform A2, but not for EDA isoform A1. Mediates the activation of the NF-kappa-B and JNK pathways. Activation seems to be mediated by binding to TRAF3 and TRAF6 (By similarity). http://togogenome.org/gene/10090:Ddx25 ^@ http://purl.uniprot.org/uniprot/Q9QY15 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATP-dependent RNA helicase. Required for mRNA export and translation regulation during spermatid development.|||Belongs to the DEAD box helicase family.|||Cytoplasm|||Isoform 1 is expressed in germ cells. Isoform 2 is expressed in Leydig cells and in round spermatids of adult testis upon gonadotropin stimulation.|||Male mice display normal sexual behavior but are sterile with testes that are 25% smaller than the wild-type. Round spermatids arrest at step 8 and fail to elongate. Chromatoid bodies are unusually condensed, greatly reduced in size and lack the typical amorphous texture throughout all steps of spermiogenesis.|||Nucleus|||Phosphorylated on threonine residues. The phosphorylated form is found in the cytoplasm but not in the nucleus. http://togogenome.org/gene/10090:Sh3bgrl2 ^@ http://purl.uniprot.org/uniprot/Q8BG73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SH3BGR family.|||Nucleus http://togogenome.org/gene/10090:St6galnac2 ^@ http://purl.uniprot.org/uniprot/P70277 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Catalyzes the transfer of N-acetylneuraminyl groups onto glycan chains in glycoproteins (PubMed:8662927). Shows a preference for N-acetylgalactosamine (GalNAc) residues already modified by the addition of galactose or galactose followed by sialic acid in alpha-2,3 linkage (PubMed:8662927).|||Golgi apparatus membrane|||Highly expressed in lactating mammary gland and adult testis. Lower levels in kidney. http://togogenome.org/gene/10090:Gnrh1 ^@ http://purl.uniprot.org/uniprot/P13562|||http://purl.uniprot.org/uniprot/Q3UTE9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GnRH family.|||Secreted|||Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.|||The precursor is cleaved by ACE, which removes the Gly-Lys-Arg peptide at the C-terminus, leading to mature hormone. The mature form of Gonadoliberin-1 is also cleaved and degraded by ACE. http://togogenome.org/gene/10090:Fmnl2 ^@ http://purl.uniprot.org/uniprot/A2APV2|||http://purl.uniprot.org/uniprot/A2AQW2|||http://purl.uniprot.org/uniprot/F8VPR2|||http://purl.uniprot.org/uniprot/Q8BI52 ^@ Similarity ^@ Belongs to the formin homology family. http://togogenome.org/gene/10090:Xlr4a ^@ http://purl.uniprot.org/uniprot/A2BI40 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Ppp4r2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0U2|||http://purl.uniprot.org/uniprot/Q0VGB7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP4R2 family.|||Nucleus|||Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4). May regulate the activity of PPP4C at centrosomal microtubule organizing centers. Its interaction with the SMN complex leads to enhance the temporal localization of snRNPs, suggesting a role of PPP4C in maturation of spliceosomal snRNPs. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on 'Ser-140' (gamma-H2AX) generated during DNA replication and required for DNA double strand break repair (By similarity). Mediates RPA2 dephosphorylation by recruiting PPP4C to RPA2 in a DNA damage-dependent manner. RPA2 dephosphorylation is required for the efficient RPA2-mediated recruitment of RAD51 to chromatin following double strand breaks, an essential step for DNA repair (By similarity).|||Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complexes PPP4C-PPP4R2, PPP4C-PPP4R2-PPP4R3A and PPP4C-PPP4R2-PPP4R3B. The PPP4C-PPP4R2 complex appears to be a tetramer composed of 2 molecules of PPP4C and 2 molecules of PPP4R2. Interacts with DDX20/GEMIN3 and GEMIN4 (By similarity). Interacts with RPA2; this DNA damage-dependent interaction recruits PPP4C leading to RPA2 dephosphorylation (By similarity).|||centrosome http://togogenome.org/gene/10090:Cops5 ^@ http://purl.uniprot.org/uniprot/O35864 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M67A family. CSN5 subfamily.|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9. In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B) and COPS9. The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interacts with CDKN1B, HIF1A, ID1 and ID3. Interacts with IFIT3. Interacts with BRSK2 (By similarity). Interacts with ZDHHC16 (By similarity). Interacts with MINDY3 (By similarity). Interacts with FANK1; regulates the phosphorylation of JUN and the transcriptional activity of AP-1 (By similarity). Interacts with NUPR1; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation (By similarity).|||Nucleus|||Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Promotes the proteasomal degradation of BRSK2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex.|||The CSN complex is associated with some 'Lys-63'-specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex (By similarity).|||The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex.|||Widely expressed.|||cytosol|||perinuclear region|||synaptic vesicle http://togogenome.org/gene/10090:Or5b102 ^@ http://purl.uniprot.org/uniprot/Q8VFW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rab11a ^@ http://purl.uniprot.org/uniprot/P62492 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Cleavage furrow|||Cytoplasmic vesicle membrane|||Endosome membrane|||Golgi apparatus|||Interacts with RAB11FIP1, RAB11FIP2, RAB11FIP3 (via its C-terminus) and RAB11FIP4 (By similarity). Interacts with EVI5; EVI5 and RAB11FIP3 may be mutually exclusive and compete for binding RAB11A (By similarity). Forms a complex with RAB11FIP3 and dynein intermediate chain DYNC1LI1; the interaction between RAB11A1 and RAB11FIP3 is direct; the complex regulates endocytic trafficking (By similarity). Interacts with RAB11FIP5 (By similarity). Interacts with STXBP6 (By similarity). Interacts (GDP-bound form) with ZFYVE27 (By similarity). Interacts with SGSM1, SGSM2, SGSM3 and VIPAS39 (PubMed:17509819, PubMed:20190753). Interacts with EXOC6 in a GTP-dependent manner (PubMed:15292201). Interacts with BIRC6/bruce (By similarity). May interact with TBC1D14 (By similarity). Interacts with UNC119; in a cell cycle-dependent manner (By similarity). GDP-bound and nucleotide-free forms interact with SH3BP5 (PubMed:26506309). Interacts (GDP-bound form) with KIF5A in a ZFYVE27-dependent manner (By similarity). Interacts (GDP-bound form) with RELCH (PubMed:29514919). Found in a complex composed of RELCH, OSBP1 and RAB11A (PubMed:29514919). Interacts with TBC1D12 (PubMed:28384198). Interacts with DEF6 (By similarity). Interacts with VPS33B (By similarity). Interacts with ATP9A (By similarity). Forms a heterotetramer with RAB11FIP3; the GTP-bound form is preferred for binding. Forms a complex with Rabin8/RAB3IP and RAB11FIP3, probably a heterohexamer with two of each protein subunit, where Rabin8/RAB3IP and RAB11FIP3 simultaneously bind to RAB11A; the complex promotes preciliary trafficking and cilia growth. Forms a complex containing RAB11A, ASAP1, Rabin8/RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport. Interacts (GTP-bound form) with WDR44; the interaction prevents RAB11A-RAB3IP-RAB11FIP3 complex formation (By similarity).|||Recycling endosome membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (By similarity). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). The small Rab GTPase RAB11A regulates endocytic recycling (By similarity). Forms a functional Rab11/FIP3/dynein complex that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (By similarity). Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes (By similarity). May also play a role in melanosome transport and release from melanocytes (PubMed:21291502). Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation. On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth (By similarity). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-endososomal dependent export route via interaction with WDR44 (By similarity).|||phagosome|||trans-Golgi network http://togogenome.org/gene/10090:Fis1 ^@ http://purl.uniprot.org/uniprot/G3X9U9|||http://purl.uniprot.org/uniprot/Q9CQ92 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FIS1 family.|||Interacts with DNM1L/DLP1 through the TPR region; may form part of a larger protein complex at the endoplasmic reticulum-mitochondrial interface during mitochondrial fission (By similarity). Interacts with MARCHF5 (By similarity). Interacts with MIEF1 (By similarity). Interacts with PEX11A, PEX11B and PEX11G (By similarity).|||Involved in the fragmentation of the mitochondrial network and its perinuclear clustering (PubMed:23283981). Plays a minor role in the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface and mitochondrial fission (PubMed:23283981). May not be essential for the assembly of functional fission complexes and the subsequent membrane scission event (By similarity). Also mediates peroxisomal fission (By similarity). May act when the products of fission are directed toward mitochondrial homeostasis, mitophagy, or apoptosis (By similarity). Can induce cytochrome c release from the mitochondrion to the cytosol, ultimately leading to apoptosis (By similarity).|||Involved in the fragmentation of the mitochondrial network and its perinuclear clustering.|||Membrane|||Mitochondrion outer membrane|||Peroxisome membrane|||The C-terminus is required for mitochondrial localization, while the N-terminus is necessary for mitochondrial fission.|||The C-terminus is required for mitochondrial or peroxisomal localization, while the N-terminus is necessary for mitochondrial or peroxisomal fission, localization and regulation of the interaction with DNM1L.|||Ubiquitinated by MARCHF5. http://togogenome.org/gene/10090:Or5k1b ^@ http://purl.uniprot.org/uniprot/E9Q8F6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gnaz ^@ http://purl.uniprot.org/uniprot/O70443|||http://purl.uniprot.org/uniprot/Q542R8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||G-proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with ADGRB2 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.|||Membrane http://togogenome.org/gene/10090:Prodh ^@ http://purl.uniprot.org/uniprot/Q9WU79 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the proline oxidase family.|||Converts proline to delta-1-pyrroline-5-carboxylate.|||Expressed in liver, kidney, heart and to a lesser extent in brain, lung and muscle.|||Mitochondrion matrix|||Pro/re mice that have a premature termination on Prodh are sluggish in their movement. http://togogenome.org/gene/10090:Rab39 ^@ http://purl.uniprot.org/uniprot/Q0PD15|||http://purl.uniprot.org/uniprot/Q8BHD0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Interacts with BECN1. Probably associates with the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex (By similarity). Interacts with UACA. Interacts with isoform a of RASSF1 (PubMed:23294242). Does not interact with isoform c of RASSF1 (PubMed:23294242).|||Lysosome|||Membrane|||Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays a role in vesicular trafficking. Plays a role in the fusion of phagosomes with lysosomes. Negatively regulates LPS-induced autophagosome formation in macrophages possibly by implicating PI3K (By similarity). May be involved in multiple neurite formation (PubMed:23624502).|||phagosome|||phagosome membrane http://togogenome.org/gene/10090:Tmem9 ^@ http://purl.uniprot.org/uniprot/Q9CR23 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM9 family.|||Expressed in heart, lung, kidney, liver and intestines (PubMed:30374053). Enriched in the hepatocytes around the central vein (PubMed:32380568).|||Interacts with the v-ATPase accessory protein ATP6AP2 and with the v-ATPase complex subunit ATP6V0D1; these interactions lead to the assembly of the v-ATPase complex.|||Knockout mice are viable and exhibit no discernible phenotypes in the overall liver architecture and hepatocytes (PubMed:30374053, PubMed:32380568). However, they display impaired hepatic regeneration with reduced Wnt signaling (PubMed:32380568). Knockout mice also show a suppression of intestinal tumorigenesis (PubMed:30374053).|||Late endosome membrane|||Lysosome membrane|||N-glycosylated.|||The transmembrane domain (TMD) is essential for the interaction with ATP6AP2.|||Transmembrane protein that binds to and facilitates the assembly of lysosomal proton-transporting V-type ATPase (v-ATPase), resulting in enhanced lysosomal acidification and trafficking (By similarity). By bringing the v-ATPase accessory protein ATP6AP2 and the v-ATPase subunit ATP6V0D1 together, allows v-ATPase complex formation and activation (By similarity). TMEM9-controlled vesicular acidification induces hyperactivation of Wnt/beta-catenin signaling, involved in development, tissue homeostasis and tissue regeneration, through lysosomal degradation of adenomatous polyposis coli/APC (PubMed:30374053, PubMed:32380568). In the liver, involved in hepatic regeneration (PubMed:32380568).|||multivesicular body membrane http://togogenome.org/gene/10090:Mlc1 ^@ http://purl.uniprot.org/uniprot/Q8VHK5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Endoplasmic reticulum|||Interacts with ATP1B1. Part of a complex containing ATP1B1, TRPV4, AQP4 and HEPACAM.|||Membrane|||Regulates the response of astrocytes to hypo-osmosis by promoting calcium influx.|||perinuclear region http://togogenome.org/gene/10090:Trim24 ^@ http://purl.uniprot.org/uniprot/Q64127 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A chromosomal aberration involving TRIM24 produces a TRIM24-BRAF (T18) oncogene originally isolated from a furfural-induced hepatoma.|||Before puberty, highly expressed in liver from males and females. After puberty, expression is considerably higher in liver from females compared to males. Up-regulated in males by continuous exposure to growth hormone.|||Cytoplasm|||Detected in embryonic and adult liver. Detected in zygote and throughout embryogenesis (at protein level). Detected in all adult tissues, with the highest expression level in testis.|||Interacts (via bromo domain) with histone H3 (via N-terminus), provided that it is not methylated at 'Lys-4' (H3K4me0). Does not interact with histone H3 that is methylated at 'Lys-4' (H3K4me1, H3K4me2 or H3K4me3). Interacts (via bromo domain) with histone H3 (via N-terminus) that is acetylated at 'Lys-23' (H3K23ac). Has the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has very low affinity for histone H3 that is methylated at 'Lys-9' (H3K9me), or acetylated at both 'Lys-9' (H3K9ac) and 'Lys-14' (H3K14ac), or acetylated at 'Lys-27' (H3K27ac) (in vitro). Interacts with TRIM16. Interacts with NR3C2/MCR (By similarity). Interacts with the ligand-binding domain of estrogen receptors (in vitro). Interaction with DNA-bound estrogen receptors requires the presence of estradiol (By similarity). Interacts with AR, CARM1, KAT5/TIP60, NCOA2/GRIP1, BRD7, CBX1, CBX3 and CBX5. Part of a coactivator complex containing TRIM24, NCOA2/GRIP1 and CARM1. Interacts with p53/TP53 and PML.|||No visible phenotype during the first few months. Impaired transition from proliferating neonatal hepatocytes to quiescent adult hepatocytes. Hepatocytes continue to proliferate throughout adulthood. High incidence hypertrophic hepatocytes with enlarged nuclei after three months. After nine months, about half of the mice have hepatocellular adenomas. Very high incidence of hepatocarcinoma in 13 to 29 month old mice, increasing from 40% to 80%. When one copy of Rara is disrupted, mice do not develop liver tumors or liver dysplasia.|||Nucleus|||Phosphorylated at Ser-768 by ATM kinase induces ubiquitination and degradation during DNA damage.|||Sumoylated.|||Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac) (By similarity). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, such as RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes. Required for normal transition from proliferating neonatal hepatocytes to quiescent adult hepatocytes.|||Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. During the DNA damage response, participates in an autoregulatory feedback loop with TP53. Early in response to DNA damage, ATM kinase phosphorylates TRIM24 leading to its ubiquitination and degradation. After sufficient DNA repair has occurred, TP53 activates TRIM24 transcription, ultimately leading to TRIM24-mediated TP53 ubiquitination and degradation (By similarity). Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes (By similarity). Participates also in innate immunity by mediating the specific 'Lys-63'-linked ubiquitination of TRAF3 leading to activation of downstream signal transduction of the type I IFN pathway. Additionally, negatively regulates NLRP3/CASP1/IL-1beta-mediated pyroptosis and cell migration probably by ubiquitinating NLRP3 (By similarity).|||Undergoes ubiquitination-mediated degradation in response to DNA damage. http://togogenome.org/gene/10090:Pgm2 ^@ http://purl.uniprot.org/uniprot/Q7TSV4 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phosphohexose mutase family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the conversion of the nucleoside breakdown products ribose-1-phosphate and deoxyribose-1-phosphate to the corresponding 5-phosphopentoses. Catalyzes the interconversion of glucose-1-phosphate into glucose-6-phosphate but with a lower catalytic efficiency. In vitro, has also a low glucose 1,6-bisphosphate synthase activity which is most probably not physiologically relevant.|||Highly expressed in lung, spleen and thymus. Expressed at lower levels in liver, brain, kidney, skeletal muscle, testis and heart.|||There is a known reversal of the Pgm1 and Pgm2 nomenclature applied to mouse versus other vertebrates. The official name of this gene in mouse is Pgm1 but it is the ortholog of other vertebrate PGM2 genes.|||cytosol http://togogenome.org/gene/10090:Twf2 ^@ http://purl.uniprot.org/uniprot/Q9Z0P5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles. May play a role in regulating the mature length of the middle and short rows of stereocilia.|||Belongs to the actin-binding proteins ADF family. Twinfilin subfamily.|||Expression was relatively weak during all of the embryonic stages. At 14.5 dpc, a slight increase in the expression could be observed in heart, CNS, and PNS. At 18.5 dpc, it is strongly expressed in the inner ear, hair cells and in the head muscles. No expression is detected in the nasal epithelium or in the skin keratinocytes.|||Interacts with G-actin; ADP-actin form and capping protein (CP). Isoform 2 interacts (via its N-terminal ADF-H domain) with G-actin (ADP-bound form) with significantly higher affinity than isoform 1. May also be able to interact with TWF1 and phosphoinositides, PI(4,5)P2. When bound to PI(4,5)P2, it is down-regulated. Interacts with MYO7A.|||Isoform 1 is ubiquitously expressed (at protein level). Isoform 2 expression is restricted to heart and skeletal muscle where it is the predominant form.|||Mice lacking isoform 1 develop normally to adulthood, are fertile, and do not exhibit obvious morphological or behavioral abnormalities.|||Phosphorylated on both serine/threonine and tyrosine.|||cytoskeleton|||perinuclear region|||stereocilium http://togogenome.org/gene/10090:Gmpr2 ^@ http://purl.uniprot.org/uniprot/Q99L27 ^@ Function|||Similarity|||Subunit ^@ Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.|||Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides (Probable). Plays a role in modulating cellular differentiation (By similarity).|||Homotetramer. http://togogenome.org/gene/10090:Ptdss2 ^@ http://purl.uniprot.org/uniprot/Q9Z1X2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Almost complete inhibition by ethanolamine in both the mitochondria-associated membrane (MAM) and endoplasmic reticulum (ER) per se.|||Belongs to the phosphatidyl serine synthase family.|||Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (PubMed:10432300, PubMed:10938271, PubMed:23071296, PubMed:12361952). Catalyzes the conversion of phosphatatidylethanolamine and does not act on phosphatidylcholine (PubMed:10938271, PubMed:23071296). Can utilize both phosphatidylethanolamine (PE) plasmalogen and diacyl PE as substrate and the latter is six times better utilized, indicating the importance of an ester linkage at the sn-1 position (PubMed:23071296). Although it shows no sn-1 fatty acyl preference, exhibits significant preference towards docosahexaenoic acid (22:6n-3) compared with 18:1 or 20:4 at the sn-2 position (PubMed:23071296).|||Endoplasmic reticulum membrane|||Highly expressed in testis. Detected at lower levels in kidney and heart.|||Membrane|||Null mice exhibit a reduction of more than 95% in serine exchange in testis and approximately 90% reduction in brain and liver. Testis weight is reduced and some animals are infertile. Elimination of either Pss1 or Pss2, but not both, is compatible with mouse viability. Mice can tolerate as little as 10% serine-exchange activity and are viable with small amounts of phosphatidylserine and phosphatidylethanolamine content. http://togogenome.org/gene/10090:Mtss1 ^@ http://purl.uniprot.org/uniprot/Q8R1S4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MTSS family.|||Binds to actin.|||Inhibits the nucleation of actin filaments in vitro.|||Strongly expressed in the developing neurons and skeletal and cardiac muscles in embryos. Strongly expressed also in liver, outer layers of the kidney, and in the Purkinje cells of the brain.|||The WH2 motif at the C-terminus binds to actin monomers.|||cytoskeleton http://togogenome.org/gene/10090:Or8d23 ^@ http://purl.uniprot.org/uniprot/Q9EQ99 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r128 ^@ http://purl.uniprot.org/uniprot/L7N2B4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sgms1 ^@ http://purl.uniprot.org/uniprot/Q8VCQ6 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ (Microbial infection) Contributes to the brain SM production for Japanese encephalitis virus attachment and infection.|||Belongs to the sphingomyelin synthase family.|||Golgi apparatus membrane|||Induced by TNF-alpha.|||Isoform 1 is widely expressed, isoform 2 shows a more narrow distribution and isoform 3 is detected only in testis and heart.|||Major sphingomyelin synthase at the Golgi apparatus (By similarity). Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER. The direction of the reaction depends on the levels of CER and DAG in Golgi membranes (By similarity). Does not use free phosphorylcholine or CDP-choline as donor. Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:22580896, PubMed:16879426) (By similarity). Plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (By similarity).|||Null mice have hearing impairments with stria vascularis (SV) in these mice exhibiting atrophy and disorganized marginal cells resulting in significantly smaller endocochlear potentials (EPs). These decreased EPs, together with abnormal KCNQ1 expression patterns, increase with age. There is a decrease in plasma, liver, and macrophage sphingomyelin (59%, 45%, and 54%, respectively) and a dramatic increase in glycosphingolipids. No change in ceramide, total cholesterol, phospholipids nor triglycerides levels. Diminished macrophage MAP kinase and NFKB1 activation is observed. Atherosclerosis in SMS1(-/-)/LDLR(-/-) mice is significantly decreased. http://togogenome.org/gene/10090:Gbp2b ^@ http://purl.uniprot.org/uniprot/A4UUI2 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. http://togogenome.org/gene/10090:Pik3r2 ^@ http://purl.uniprot.org/uniprot/O08908 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the PI3K p85 subunit family.|||Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL. Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated) (By similarity). Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex. Interacts with PTPN13; dephosphorylates PIK3R2 (By similarity). Interacts with NYAP1, NYAP2 and MYO16 (PubMed:21946561). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner (PubMed:20348926). Interacts with SRC (By similarity).|||Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Dephosphorylated at Tyr-649 by PTPN13. Phosphorylation of Tyr-649 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination.|||Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy (By similarity). Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348926).|||The SH2 2 domain is required for interaction with FBXL2 and PTPN13.|||Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2. http://togogenome.org/gene/10090:Gal3st4 ^@ http://purl.uniprot.org/uniprot/E9Q7N6|||http://purl.uniprot.org/uniprot/Q3V1B8 ^@ Similarity ^@ Belongs to the galactose-3-O-sulfotransferase family. http://togogenome.org/gene/10090:Kpnb1 ^@ http://purl.uniprot.org/uniprot/P70168|||http://purl.uniprot.org/uniprot/Q3UHW8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the importin beta family. Importin beta-1 subfamily.|||Cytoplasm|||Forms a complex with an importin alpha subunit (By similarity). Interacts with XPO1 (By similarity). Forms a heterodimer with IPO7 (By similarity). The KPNB1/IPO7 heterodimer interacts with H1 histone (By similarity). Interacts with SNUPN (By similarity). Interacts with H2A, H2B, H3 and H4 histones (PubMed:11493596). Component of an import snRNP complex composed of KPNB1, SNUPN, SMN1 and ZNF259 (By similarity). Component of a nuclear export receptor complex composed of KPNB1, Ran, SNUPN and XPO1 (By similarity). Interacts with SRY (PubMed:11535586). Interacts with PRKCI/atypical protein kinase C iota (By similarity). Interacts with KPNA2 (By similarity). Interacts with KPNA7 (PubMed:20699224). Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc fingers) (By similarity). Interacts with SLC35G1 and STIM1 (By similarity). Interacts with DCAF8 (By similarity). Interacts with RAN (PubMed:25946333). Interacts with NUMA1 (via C-terminus); this interaction is inhibited by RanGTP (By similarity). Interacts with ZBED1/hDREF; required for nuclear import of ZBED1/hDREF (By similarity). Interacts with SRP19 (By similarity). Interacts with RPL23A (via BIB domain), RPS7 and RPL5 (By similarity). Interacts with PARP16 (By similarity).|||Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor. Acting autonomously, serves itself as NLS receptor. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5. In association with IPO7, mediates the nuclear import of H1 histone. In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. Imports SNAI1 and PRKCI into the nucleus (By similarity).|||Mono-ADP-ribosylated by PARP16.|||Nucleus envelope http://togogenome.org/gene/10090:Lpar2 ^@ http://purl.uniprot.org/uniprot/Q9JL06 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cell surface|||Interacts with SLC9A3R2/NHERF2, MAGI3 and PLCB3. Interacts with RALA and GRK2 (By similarity).|||Most abundantly expressed in testes, kidney, and embryonic brain. Other organs also express the transcript, including heart, lung, spleen, thymus, stomach, and adult brain. Several have little or no expression, including liver, small intestine, and skeletal muscle.|||Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Plays a key role in phospholipase C-beta (PLC-beta) signaling pathway Stimulates phospholipase C (PLC) activity in a manner that is independent of RALA activation (By similarity). http://togogenome.org/gene/10090:Mme ^@ http://purl.uniprot.org/uniprot/Q61391 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M13 family.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.|||Mice are overtly normal in appearance and size and do not show obvious abnormalities in motor performance or coordination. Nerve conduction studies reveal no significant differences between mutant and control animals.|||Myristoylation is a determinant of membrane targeting.|||Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (By similarity). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (By similarity). Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (By similarity). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (By similarity). Involved in the degradation of the atrial natriuretic factor (ANF) (By similarity). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573). http://togogenome.org/gene/10090:Or5g29 ^@ http://purl.uniprot.org/uniprot/Q8VF76 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Iqschfp ^@ http://purl.uniprot.org/uniprot/A0A088MLT8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Based on a naturally occurring readthrough transcript which produces an IQCJ-SCHIP1 fusion protein.|||Cytoplasm|||Homooligomer (via coiled coil domain) (PubMed:27979964). Interacts (via IQ domain) with calmodulin; the interaction is direct and lost in presence of calcium (PubMed:18550753). Interacts with ANK3 (via ANK repeats); required for its localization at axon initial segments (AIS) and nodes of Ranvier (PubMed:18550753). Interacts with SPTBN4 (PubMed:27979964). Interacts with KCNQ2 and KCNQ3 (PubMed:27979964).|||May play a role in action potential conduction in myelinated cells through the organization of molecular complexes at nodes of Ranvier and axon initial segments (PubMed:25953347, PubMed:25950943, PubMed:27979964). May also play a role in axon outgrowth and guidance (PubMed:25953347).|||Mice lacking all isoforms encoded by both Schip1 and Iqcj-Schip1 are fertile and survive as long as wild-type mice. However, they exhibit mild growth delay associated with ataxia and reduced pain sensitivity. They display decreased thickness of the piriform cortex and partial agenesis of the anterior comissure which could be due to impaired axon elongation and guidance. The morphology of nodes of Ranvier is affected but nerves do not exhibit significant electrophysiological characteristic differences. A reduction in the number of axonal projections in the peripheral nerve system is also observed.|||axon http://togogenome.org/gene/10090:Flnb ^@ http://purl.uniprot.org/uniprot/Q80X90 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the filamin family.|||Comprised of a NH2-terminal actin-binding domain, 24 internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. The first hinge region prevents binding to ITGA and ITGB subunits (By similarity).|||Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton (By similarity).|||Expressed in hippocampus, cortex, cerebellar Purkinje cells and granule cell layers.|||Expressed within the ventricular, periventricular and subventricular zones at 12.5 dpc; olfactory epithelium, radial glial fibers, cortical plate and lateral ventricles at 16 dpc; in a lesser degree in lung, renal cortices and alimentary tract.|||Homodimer. Interacts with FLNA, FLNC, INPPL1, ITGB1A, ITGB1D, ITGB3, ITGB6, MYOT, MYOZ1, PSEN1 and PSEN2 (By similarity). Interacts with MICALL2. Interacts with RFLNA and RFLNB (PubMed:21709252, PubMed:24436304). Interacts with ASB2 isoform 1; the interaction targets FLNB for proteasomal degradation (PubMed:26343497).|||ISGylation prevents ability to interact with the upstream activators of the JNK cascade and inhibits IFNA-induced JNK signaling.|||Ubiquitination by a SCF-like complex containing ASB2 isoform 1 leads to proteasomal degradation which promotes muscle differentiation.|||Z line|||cell cortex|||cytoskeleton|||stress fiber http://togogenome.org/gene/10090:Gtf2a1l ^@ http://purl.uniprot.org/uniprot/Q8R4I4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TFIIA subunit 1 family.|||Expressed from 14 days postnatal day.|||May function as a testis specific transcription factor. Binds DNA in conjunction with GTF2A2 and TBP (the TATA-binding protein) and together with GTF2A2, allows mRNA transcription.|||Nucleus|||Testis specific. Expressed in pachytene spermatocytes and haploid spermatids. http://togogenome.org/gene/10090:Zic2 ^@ http://purl.uniprot.org/uniprot/F8VPV3 ^@ Similarity ^@ Belongs to the GLI C2H2-type zinc-finger protein family. http://togogenome.org/gene/10090:Il6st ^@ http://purl.uniprot.org/uniprot/Q00560|||http://purl.uniprot.org/uniprot/Q6PDI9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Cell membrane|||Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; associates with the complex IL6:IL6R but does not interact with IL6 (By similarity). Forms heterodimers composed of LIFR and IL6ST (type I OSM receptor) which are activated by LIF and OSM. Also forms heterodimers composed of OSMR and IL6ST (type II receptor) which are activated by OSM but not by LIF. Interacts with HCK (By similarity). Interacts with INPP5D/SHIP1 (PubMed:17105399). Interacts with SRC and YES (By similarity). Interacts with ARMH4; this interaction prevents IL6ST protein homodimerization and bridges ARMH4 with IL6R and STAT3 and therefore inhibits phosphorylation of STAT3 at 'Tyr-705' (By similarity).|||Expression not restricted to IL6-responsive cells. Found in tissues such as brain, heart, thymus, spleen, kidney, lung and liver. Found in all the cell lines tested except BaF-B03. Expressed paraventricular nucleus of the hypothalamus (PubMed:28402851).|||Heavily N-glycosylated. Glycosylation is required for protein stability and localization in plasma membrane but not for ligand binding.|||In embryonic stem cells it is found from day 6 of gestation. It reaches a peak on day 8 and gradually declines during the rest of embryogenesis.|||In paraventricular nucleus of the hypothalamus, expression is enhanced by obesity.|||Membrane|||Phosphorylation of Ser-780 down-regulates cell surface expression.|||Progressively lethal between 12.5 dpc and birth (PubMed:8552649). Embryos show hypoplastic ventricular myocardium without septal and trabecular defect, reduced numbers of pluripotential and committed hematopoietic progenitors in liver and reduced differentiated lineages in thymus (PubMed:8552649). Impaired differentiation of astrocytes and decreased number of dorsal root ganglion and motor neurons at 18.5 dpc (PubMed:10377352). Decreased volume of mineralized trabecular bones, while number of osteoclasts is increased (PubMed:9348227, PubMed:26255596). Conditional knockout from the entire osteoblast lineage or specifically in osteocytes causes no significant skeletal or morphological defects but mice show 30% lower trabecular bone formation rate and larger cortical diameter compared to wild type (PubMed:24339143, PubMed:26255596). Conditional knockout in primary nociceptive afferents causes reduced sensitivity to mechanical stimulation due to reduced sensitivity of nociceptive neurons and reduces TRPA1 mRNA expression in dorsal root ganglion neurons (PubMed:25057188).|||Signal-transducing molecule (PubMed:1602143). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways (PubMed:1602143, PubMed:10661409). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:10661409). In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (PubMed:9202125). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (PubMed:25731159). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (PubMed:10661409, PubMed:26255596, PubMed:25057188, PubMed:8552649). Has a role in embryonic development (PubMed:10661409). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (PubMed:10377352). Required for expression of TRPA1 in nociceptive neurons (PubMed:25057188). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (PubMed:25228504). Required for normal trabecular bone mass and cortical bone composition (PubMed:24339143, PubMed:9348227, PubMed:26255596).|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Siah2 ^@ http://purl.uniprot.org/uniprot/Q06986|||http://purl.uniprot.org/uniprot/Q3UEV2 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SINA (Seven in absentia) family.|||Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:24809345, PubMed:26070566). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. Promotes monoubiquitination of SNCA (By similarity). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP) (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes (PubMed:11257006, PubMed:14645235, PubMed:14645526, PubMed:17003045, PubMed:9637679, PubMed:26070566). Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation (By similarity). Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance (PubMed:26392558). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (PubMed:24809345). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (By similarity).|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.|||Homodimer (By similarity). Interacts with UBE2E2 (By similarity). Interacts with VAV1, without mediating its ubiquitin-mediated degradation (By similarity). Interacts with CACYBP/SIP (By similarity). Probable component of some large E3 complex possibly composed of UBE2D1, SIAH2, CACYBP/SIP, SKP1, APC and TBL1X (By similarity). Interacts with UBE2I (By similarity). Interacts with PEG10, which may inhibit its activity (By similarity). Interacts with EGLN2 and SNCAIP (By similarity). Interacts with DYRK2 (By similarity). Interacts with PEG3 (PubMed:10681424). Interacts with NR1D1 and NR1D2 (By similarity). Interacts with DCC (By similarity). Interacts with AXIN1.|||May be induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response (PubMed:12417719). The relevance of such activity in vivo is however unclear and may not exist (PubMed:12417719). Induced by ATF4 in response to the unfolded protein response (UPR) (PubMed:24809345).|||Nucleus|||Phosphorylated at Ser-29 by DYRK2; this increases the ubiquitin ligase activity and promotes degradation of EGLN3 (By similarity). Phosphorylated at Thr-24 and Ser-29 by MAPK14, which mediates the degradation by the proteasome of EGLN3.|||The RING-type zinc finger domain is essential for ubiquitin ligase activity.|||The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.|||The SBD domain (substrate-binding domain) mediates the interaction with substrate proteins. It is related to the TRAF family.|||Widely expressed at low level in embryos and adults. Expressed in a specific population of germ cells within both the mouse ovary and testis. Absent in primordial oocytes but expressed in all growing oocytes, coincident with their recruitment from the pool of quiescent cells. Its level of expression increases as the oocytes mature. Expressed in Graafian follicles and in fertilized zygotes up until the two cell stage, a time of extensive maternal transcript degradation and zygotic gene activation. Expressed in the testis from postmeiotic spermatids. http://togogenome.org/gene/10090:Glycam1 ^@ http://purl.uniprot.org/uniprot/A0A2I3BPT0|||http://purl.uniprot.org/uniprot/Q02596 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adhesion molecule that accomplishes cell binding by presenting carbohydrate(s) to the lectin domain of L-selectin.|||Belongs to the PP3/GlyCAM-1 family.|||Cell membrane|||Extensively O-glycosylated.|||Lymph nodes. Associated with the lumenal surface of the high endothelial venules of peripheral lymph nodes. http://togogenome.org/gene/10090:Cox4i2 ^@ http://purl.uniprot.org/uniprot/Q91W29 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase IV family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lrrc3 ^@ http://purl.uniprot.org/uniprot/P59034 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the LRRC3 family.|||Membrane http://togogenome.org/gene/10090:Cntn3 ^@ http://purl.uniprot.org/uniprot/Q07409 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. Contactin family.|||Cell membrane|||Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity (By similarity).|||Interacts with PTPRG.|||Specifically expressed in brain. Ectopically expressed in tumors expressing endogenous intracisternal A-type particles (IAPs). http://togogenome.org/gene/10090:Obox3 ^@ http://purl.uniprot.org/uniprot/Q3UT54 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pin1 ^@ http://purl.uniprot.org/uniprot/Q9QUR7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals display more and larger germinal centers (PubMed:17828269). In response to intranasal administration of IL33, lung inflammation is reduced compared to wild-type and is associated with low infiltration by inflammatory cells, especially granulocytes, a severe reduction in Th2-type cytokine secretion, including Il4, Il5 and Il13 in bronchial alveolar fluids, and reduced up-regulation of Il6, Csf3, Cxcl2 and Ccl5 mRNAs (PubMed:29686383). In addition, the increase in IRAK3/IRAK-M protein levels in infiltrated inflammatory cells is impaired (PubMed:29686383). In an ovalbumin-induced model of allergic asthma, causes reduced lung inflammation and, reduced Th2-type cytokine levels and inflammatory cell infiltration in bronchial alveolar fluids (PubMed:29686383).|||Cytoplasm|||Expressed in dendritic cells (at protein level).|||Interacts with STIL (PubMed:16024801). Interacts with KIF20B. Interacts with NEK6. Interacts (via WW domain) with PRKX (PubMed:19367327). Interacts with BTK. Interacts (via PpiC domain) with DAPK1. Interacts with the phosphorylated form of RAF1. Interacts (via WW domain) with ATCAY; upon NGF stimulation. Interacts with PML. Interacts with BCL6. Interacts with FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity). Directly interacts with RBBP8/CtIP; this interaction depends upon RBBP8 phosphorylation (By similarity). Interacts (via WW domain) with IRAK3/IRAK-M (when phosphorylated at 'Ser-110') in response to IL33-mediated (but not TLR4 ligand LPS) dendritic cell stimulation (PubMed:29686383).|||Nucleus|||Nucleus speckle|||Peptidyl-prolyl cis/trans isomerase (PPIase) that binds to and isomerizes specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs (PubMed:29686383). By inducing conformational changes in a subset of phosphorylated proteins, acts as a molecular switch in multiple cellular processes. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation (By similarity). Binds and targets PML and BCL6 for degradation in a phosphorylation-dependent manner (PubMed:17828269). Acts as a regulator of JNK cascade by binding to phosphorylated FBXW7, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation: degradation of FBXW7 leads to subsequent stabilization of JUN (By similarity). May facilitate the ubiquitination and proteasomal degradation of RBBP8/CtIP through CUL3/KLHL15 E3 ubiquitin-protein ligase complex, hence favors DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (By similarity). Upon IL33-induced lung inflammation, catalyzes cis-trans isomerization of phosphorylated IRAK3/IRAK-M, inducing IRAK3 stabilization, nuclear translocation and expression of pro-inflammatory genes in dendritic cells (PubMed:29686383).|||Phosphorylation at Ser-73 by DAPK1 results in inhibition of its catalytic activity, nuclear localization, and its ability to induce centrosome amplification, chromosome instability and cell transformation (By similarity). Ser-73 is dephosphorylated upon IL33-stimulation of dendritic cells (PubMed:29686383).|||The WW domain is required for the interaction with STIL and KIF20B. http://togogenome.org/gene/10090:Atxn1 ^@ http://purl.uniprot.org/uniprot/J3QPR1|||http://purl.uniprot.org/uniprot/P54254 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atxn1 protein levels are directly regulated by Pum1 protein: Pum1 acts by binding to the 3'-UTR of Atxn1 mRNA, affecting Atxn1 mRNA stability and leading to reduced Atxn1 protein levels.|||Belongs to the ATXN1 family.|||Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression (By similarity). May be involved in RNA metabolism (By similarity). In concert with CIC and ATXN1L, involved in brain development (PubMed:28288114).|||Cytoplasm|||Different transgenic mouse, containing a poly-Gln region insertion in position 199 have been developed to replicate phenotypes of the spinocerebellar ataxia 1 disease (SCA1) in human (PubMed:10624951, PubMed:12086639). Heterozygous mice with a poly-Gln of 92 residues [92Q] develop the ataxia typical of human SCA1. However, they show only the phenotype associated with dysfunctional Purkinje cells and usually live a normal lifespan (PubMed:10624951). Heterozygous mice with a poly-Gln of 154 residues [154Q] develop a progressive neurological disorder that resembles human SCA1, with motor incoordination, cognitive deficits, wasting, and premature death, accompanied by Purkinje cell loss and age-related hippocampal synaptic dysfunction (PubMed:12086639). Phenotypes are caused by an accumulation of Atxn1 in neurons, exerting toxicity. The expanded poly-Gln tract causes stabilization of Atxn1 and impairs its ubiquitination and subsequent degradation, increasing its abundance in neurons (PubMed:10624951).|||Expressed in the cortex and hypothalamus (at protein level). Widely expressed. In brain, the pattern of distribution is limited to neuron populations.|||Homooligomer (By similarity). Interacts with PQBP1, UBQLN4 and USP7 (By similarity). Interacts with ANP32A (PubMed:9353121). Interacts with CIC (PubMed:17190598). Directly interacts with RBPJ; this interaction is disrupted in the presence of Notch intracellular domain. Interacts with ATXN1L; competes with ATXN1L for RBPJ-binding (PubMed:17322884). Found in a complex with CIC and ATXN1L (PubMed:28288114).|||Mice with conditional knockouts of either ATXN1-ATXN1L or CIC in the developing forebrain exhibit intellectual disability, hyperactivity, social-behavioral deficits and reduced thickness of upper cortical layers.|||Nucleus|||Sumoylation is dependent on nuclear localization and phosphorylation at Ser-751.|||The AXH domain is required for interaction with CIC.|||The murine poly-Gln region is very limited in comparison to human ATXN1 and is not polymorphic.|||Transient expression burst in Purkinje cells as the cerebellar cortex becomes functional (postnatal day 14), and in mesenchymal cells of the developing intervertebral disks of the spinal column.|||Ubiquitinated by UBE3A, leading to its degradation by the proteasome. The presence of poly-Gln repeats in trangenic models developed to replicate phenotypes of the spinocerebellar ataxia 1 disease (SCA1) impair ubiquitination and degradation, leading to accumulation of Atxn1 in neurons and subsequent toxicity. http://togogenome.org/gene/10090:Add1 ^@ http://purl.uniprot.org/uniprot/E9Q1K3|||http://purl.uniprot.org/uniprot/F8WGR0|||http://purl.uniprot.org/uniprot/F8WHZ9|||http://purl.uniprot.org/uniprot/Q9QYC0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the aldolase class II family. Adducin subfamily.|||Cell membrane|||Each subunit is comprised of three regions: a NH2-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.|||Heterodimer of an alpha and a beta subunit or an alpha and a gamma subunit.|||Membrane|||Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin.|||cytoskeleton http://togogenome.org/gene/10090:St7l ^@ http://purl.uniprot.org/uniprot/Q8K4P7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ST7 family.|||Membrane|||Ubiquitously expressed. http://togogenome.org/gene/10090:Yipf2 ^@ http://purl.uniprot.org/uniprot/Q99LP8 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the YIP1 family.|||Interacts with YIPF6; this interaction may stabilize YIPF2. May also form a ternary complex with YIPF1 and YIPF6.|||Late endosome membrane|||cis-Golgi network membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Atr ^@ http://purl.uniprot.org/uniprot/A0A1L1SSL9|||http://purl.uniprot.org/uniprot/E9QPK4 ^@ Similarity ^@ Belongs to the PI3/PI4-kinase family. ATM subfamily. http://togogenome.org/gene/10090:Cxcr2 ^@ http://purl.uniprot.org/uniprot/P35343 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with IL8. Interacts with GNAI2.|||Phosphorylated upon ligand binding; which is required for desensitization.|||Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2. http://togogenome.org/gene/10090:Mgat4d ^@ http://purl.uniprot.org/uniprot/Q9D4R2 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 54 family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Expression of isoform 1 and isoform 2 is up-regulated in testis at postnatal day 17; isoform 1 maintains similar expression levels until the adult; expression of isoform 2 peaks at postnatal day 22 and is barely detected in the adult.|||For isoform 1 inhibition of MGAT1 activity is demonstrated in vitro upon forced membrane-association. Its rat ortholog is the most abundant protein in testis Golgi preparations.|||Golgi apparatus membrane|||Isoform 1 and isoform 2 are specifically expressed in testis. Isoform 2 is expressed in spermatocytes but not in spermatids. Isoform 1 is expressed in spermatids.|||Isoform 2 is N-glycosylated; consisting of high-mannose and/or hybrid glycans.|||Isoform 2 self-associates; specifically in the endoplasmic reticulum prior to its translocation to the Golgi. Isoform 1 and isoform 2 interact with MGAT1, MGAT3 and MAN2A2; isoform 2 interacts specifically with MGAT1 in the Golgi.|||May play a role in male spermatogenesis. In vitro acts as inhibitor of MGAT1 activity causing cell surface proteins to carry mainly high mannose N-glycans. The function is mediated by its lumenal domain and occurs specifically in the Golgi. A catalytic glucosyltransferase activity is not detected. May be involved in regulation of Sertoli-germ cell interactions during specific stages of spermatogenesis. http://togogenome.org/gene/10090:Clec4n ^@ http://purl.uniprot.org/uniprot/Q9JKF4 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A short stretch of the intracellular domain (AA 8-14) proximal to the transmembrane domain is required for association with Fc receptor gamma chain.|||Associated with FCER1G (PubMed:17050534). Heterodimer with CLEC4D; this heterodimer forms a pattern recognition receptor (PRR) against fungal infection (By similarity).|||Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: specifically recognizes and binds alpha-mannans on C.albicans hypheas (PubMed:17050534, PubMed:19703985, PubMed:20493731). Binding of C.albicans alpha-mannans to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes (PubMed:17050534, PubMed:19703985, PubMed:20493731, PubMed:32358020). Recognizes also, in a mannose-dependent manner, allergens from house dust mite and fungi, by promoting cysteinyl leukotriene production (PubMed:19124755). Recognizes soluble elements from the eggs of Shistosoma mansoni altering adaptive immune responses (PubMed:21059925).|||Cell membrane|||Deficient mice are healthy, fertile, with normal lymphoid cells, but show reduced survival after intravenous Candida albicans infection (PubMed:20493731). In deficient mice fungal burden is higher in kidneys of mutant and in response to yeast antigen inflammatory cytokines and Th17 cells are reduced (PubMed:20493731).|||Expressed by the XS52 DC (dendritic cell) line (at protein level). Expressed constitutively by the epidermis, and skin resident DC appear to be the major source of this expression. Expressed in the spleen and thymus. Expression was undetectable in non-DC lines, including macrophage lines (J774 and Raw), T-cell lines (7-17, HDK-1, and D10), B-cell hybridoma (5C5), a keratinocyte line (Pam 212), and a fibroblast line (NS01). http://togogenome.org/gene/10090:Kctd12 ^@ http://purl.uniprot.org/uniprot/Q6WVG3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization.|||Expressed in the brain, mainly in the hippocampus and cerebellum.|||Interacts as a tetramer with GABRB1 and GABRB2.|||Postsynaptic cell membrane|||Presynaptic cell membrane http://togogenome.org/gene/10090:Pomc ^@ http://purl.uniprot.org/uniprot/P01193 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ACTH and MSH are produced by the pituitary gland.|||Anorexigenic peptide. Increases the pigmentation of skin by increasing melanin production in melanocytes.|||Belongs to the POMC family.|||Endogenous opiate.|||Endogenous orexigenic opiate.|||In hypothalamic paraventricular nucleus (PVN), up-regulated by cannabinoids, including the CNR1/CB1R agonist arachidonyl-29-chloroethylamide (ACEA) (at protein level).|||Increases the pigmentation of skin by increasing melanin production in melanocytes.|||Secreted|||Specific enzymatic cleavages at paired basic residues yield the different active peptides.|||Stimulates the adrenal glands to release cortisol. http://togogenome.org/gene/10090:Cyp2c37 ^@ http://purl.uniprot.org/uniprot/P56654|||http://purl.uniprot.org/uniprot/Q9DBD9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that metabolizes (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) to primarily produce 12-hydroxyeicosatetraenoic acid (12-HETE). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Liver.|||Microsome membrane http://togogenome.org/gene/10090:Syt17 ^@ http://purl.uniprot.org/uniprot/Q920M7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the synaptotagmin family.|||Membrane|||Plays a role in dendrite formation by melanocytes. http://togogenome.org/gene/10090:Smad4 ^@ http://purl.uniprot.org/uniprot/P97471 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dwarfin/SMAD family.|||Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling. Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity). Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (PubMed:15329343). Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (PubMed:15329343). In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8.|||Conditional knockout in muscle leads to muscle atrophy and weakness. Mutant mice loose significantly more muscle mass after denervation as compared to wild-type animals and show excessive proteolysis in denervated muscle. The loss of maximal absolute force after fasting is greater in mutant mice than in controls.|||Cytoplasm|||Monomer; in the absence of TGF-beta activation (By similarity). Heterotrimer; on TGF-beta activation (By similarity). Heterotrimer composed of two molecules of a C-terminally phosphorylated R-SMAD molecule, SMAD2 or SMAD3, and one molecule of SMAD4 to form the transcriptional active SMAD2/SMAD3-SMAD4 complex (PubMed:21145499). Found in a ternary complex composed of SMAD4, STK11/LKB1 and STK11IP. Interacts with ATF2, COPS5, DACH1, MSG1, SKI, STK11/LKB1, STK11IP and TRIM33. Found in a complex with SMAD1 and YY1 (PubMed:15329343). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (By similarity). Associates with ZNF423 or ZNF521 in response to BMP2 leading to activate transcription of BMP target genes. Interacts with USP9X. Interacts with RBPMS. Interacts with WWTR1 (via coiled-coil domain). Interacts with CITED1 and CITED2 (By similarity). Interacts with PDPK1 (via PH domain) (By similarity). Interacts with VPS39; this interaction affects heterodimer formation with SMAD3, but not with SMAD2, and leads to inhibition of SMAD3-dependent transcription activation (By similarity). Interactions with VPS39 and SMAD2 may be mutually exclusive (By similarity). Interacts (via MH2 domain) with ZNF451 (via N-terminal zinc-finger domains) (By similarity). Found in a complex with SMAD1 and YY1 (PubMed:15329343). Interacts with ZC3H3 (PubMed:16115198). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with NUP93 and IPO7; translocates SMAD4 to the nucleus through the NPC upon BMP7 stimulation resulting in activation of SMAD4 signaling (By similarity). Interacts with CREB3L1, the interaction takes place upon TGFB1 induction and SMAD4 acts as CREB3L1 coactivator to induce the expression of genes involved in the assembly of collagen extracellular matrix (By similarity). Interacts with DLX1 (By similarity). Interacts with ZBTB7A; the interaction is direct and stimulated by TGFB1 (By similarity). Interacts with CREBBP; the recruitment of this transcriptional coactivator is negatively regulated by ZBTB7A (By similarity). Interacts with EP300; the interaction with this transcriptional coactivator is negatively regulated by ZBTB7A (By similarity). Interacts with HDAC1 (By similarity). Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (By similarity). Interacts (via N-terminus) with TSC22D1 (By similarity).|||Monoubiquitinated on Lys-518 by E3 ubiquitin-protein ligase TRIM33. Monoubiquitination hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination by USP9X restores its competence to mediate TGF-beta signaling (By similarity).|||Nucleus|||Phosphorylated by PDPK1.|||The MH1 domain is required for DNA binding.|||The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Or11g25 ^@ http://purl.uniprot.org/uniprot/L7N1Y5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Car1 ^@ http://purl.uniprot.org/uniprot/P13634 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-carbonic anhydrase family.|||Catalyzes the reversible hydration of carbon dioxide. Can hydrate cyanamide to urea.|||Cytoplasm|||Inhibited by acetazolamide. http://togogenome.org/gene/10090:Vmn2r82 ^@ http://purl.uniprot.org/uniprot/G3UWA2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Eri2 ^@ http://purl.uniprot.org/uniprot/Q5BKS4 ^@ Cofactor|||Similarity ^@ Belongs to the ERI2 family.|||Binds 2 magnesium ions per subunit. http://togogenome.org/gene/10090:Hes5 ^@ http://purl.uniprot.org/uniprot/P70120 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).|||Nucleus|||The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.|||Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.|||Transcriptional repressor of genes that require a bHLH protein for their transcription. Plays an important role as neurogenesis negative regulator. http://togogenome.org/gene/10090:Spout1 ^@ http://purl.uniprot.org/uniprot/Q3UHX9 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class IV-like SAM-binding methyltransferase superfamily.|||Interacts with INCA1.|||May be due to intron retention.|||Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase. Also involved in chromosome alignment. May promote centrosome maturation probably by recruiting A-kinase anchor protein AKAP9 to centrosomes in early mitosis. Binds specifically to miRNA MIR145 hairpin, regulates MIR145 expression at a postranscriptional level (By similarity).|||centrosome|||kinetochore|||spindle http://togogenome.org/gene/10090:Snu13 ^@ http://purl.uniprot.org/uniprot/Q9D0T1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL8 family.|||Identified in the spliceosome B complex. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, NHP2L1, EFTUD2, SART1 and USP39. Interacts with RAD17 and PRPF31. The complex formed by SNU13 and PRPF31 binds U4 snRNA. The complex formed by SNU13 and PRPF31 binds also U4atac snRNA, a characteristic component of specific, less abundant spliceosomal complexes. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Nucleus|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in pre-mRNA splicing as component of the spliceosome. Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly. The protein undergoes a conformational change upon RNA-binding.|||nucleolus http://togogenome.org/gene/10090:Kcnj5 ^@ http://purl.uniprot.org/uniprot/P48545 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ5 subfamily.|||May associate with GIRK1 and GIRK2 to form a G-protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger.|||Membrane|||Predominantly atrial and pancreatic expression.|||This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium. http://togogenome.org/gene/10090:Gprasp2 ^@ http://purl.uniprot.org/uniprot/Q8BUY8 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the GPRASP family.|||Interacts with cytoplasmic tails of a variety of G-protein coupled receptors such as muscarinic acetylcholine receptor M1/CHRM1 and calcitonin receptor/CALCR.|||May play a role in regulation of a variety of G-protein coupled receptors.|||Strongly expressed in the brain and the cochlea. Also in lung and muscle tissues. Localized in multiple structures of the cochlea, detected in the spiral ganglion, stria vascularis, spiral ligament, inner and outer hair cells. http://togogenome.org/gene/10090:Npy6r ^@ http://purl.uniprot.org/uniprot/Q61212 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in embryo at 7 dpc.|||Kidney and discrete regions of the hypothalamus including the suprachiasmatic nucleus, anterior hypothalamus, bed nucleus stria terminalis, and the ventromedial nucleus.|||Receptor for neuropeptide Y and peptide YY. The rank order of affinity of this receptor for pancreatic polypeptides is NPY = PYY >= NPY (2-36) = [Leu-31, Pro-34] NPY > NPY (13-36) > PP. The activity of this receptor is mediated by G proteins that inhibits adenylate cyclase activity.|||Was originally called NPY5-R. http://togogenome.org/gene/10090:Ampd2 ^@ http://purl.uniprot.org/uniprot/Q9DBT5 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subunit ^@ AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle.|||Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.|||Binds 1 zinc ion per subunit.|||Homotetramer.|||Mice have normal brain histology. http://togogenome.org/gene/10090:Atad1 ^@ http://purl.uniprot.org/uniprot/Q9D5T0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ About 80% of the mutant mice die of a seizure-like syndrome between postnatal days 19 and 25; the remaining 20% survive up to 8 weeks of age. No gross abnormalities in tissues analyzed, including heart, lung, spleen, kidney, thymus, liver, intestine, testis, eyes, and muscle. In the CA1 region of the hippocampus, no substantial difference in the dendritic complexity or in the number or size of dendritic spines and normal density of synapses in mutant animals compared to wild-type.|||Belongs to the AAA ATPase family. MSP1 subfamily.|||Interacts with GRIA2 and GRIP1 in an ATP-dependent manner (PubMed:21496646). ATAD1-catalyzed ATP hydrolysis disrupts not only its binding to GRIA2 and GRIP1, but also interaction between GRIP1 and GRIA2, leading to AMPAR complex disassembly (PubMed:21496646).|||Mitochondrion outer membrane|||Outer mitochondrial translocase required to remove mislocalized tail-anchored transmembrane proteins on mitochondria (By similarity). Specifically recognizes and binds tail-anchored transmembrane proteins: acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins from the mitochondrion outer membrane (By similarity). Also plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory (PubMed:21496646). Required for NMDA-stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent (PubMed:21496646).|||Peroxisome membrane|||Postsynaptic cell membrane|||Widely expressed with the highest expression in the brain and testis. In the brain, relatively high expression in hippocampal CA1 pyramidal cells (at protein level). http://togogenome.org/gene/10090:Mynn ^@ http://purl.uniprot.org/uniprot/Q99MD8 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expression is developmentally regulated in muscle and is associated with neuromuscular junctions during the late embryonic period.|||Mainly expressed in the neuromuscular system. Located in and around synaptic myonuclei in adult muscle. Expression is dysregulated after nerve injury. Also found in the cerebellum, testis, heart, brain and liver.|||Nucleus http://togogenome.org/gene/10090:Vmn1r260 ^@ http://purl.uniprot.org/uniprot/K9J7F4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pdxk ^@ http://purl.uniprot.org/uniprot/Q8K183 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is increased in the presence of K(+)or Na(+).|||Belongs to the pyridoxine kinase family.|||Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (By similarity). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions (By similarity).|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Pelo ^@ http://purl.uniprot.org/uniprot/Q80X73 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic release factor 1 family. Pelota subfamily.|||Component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway. In the Pelota-HBS1L complex, PELO recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel. Following mRNA extraction from stalled ribosomes by the SKI complex, the Pelota-HBS1L complex promotes recruitment of ABCE1, which drives the disassembly of stalled ribosomes, followed by degradation of damaged mRNAs as part of the NGD pathway. As part of the PINK1-regulated signaling, upon mitochondrial damage is recruited to the ribosome/mRNA-ribonucleoprotein complex associated to mitochondrial outer membrane thereby enabling the recruitment of autophagy receptors and induction of mitophagy.|||Component of the Pelota-HBS1L complex, also named Dom34-Hbs1 complex, composed of PELO and HBS1L. Interacts with PINK1. Interacts with ABCE1. Interacts with CNOT4.|||Cytoplasm|||Embryonic lethality due to defects in chromosome segregation during cell division, resulting in aneuploidy and loss of genomic stability.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Mark3 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VNZ6|||http://purl.uniprot.org/uniprot/Q03141 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564 (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cell membrane|||Cytoplasm|||Interacts with MAPT/TAU (By similarity). Interacts with DLG5 (via coiled-coil domain) (By similarity). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5 (By similarity). Interacts with YWHAB, YWHAG, YWHAQ and YWHAZ (By similarity). Interacts with PKP2 (via N-terminus) (By similarity). Interacts with CDC25C (By similarity). Interacts with KSR1 (PubMed:12941695).|||Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity (By similarity).|||Serine/threonine-protein kinase. Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU. Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol. Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1. Phosphorylates PKP2 and KSR1.|||dendrite http://togogenome.org/gene/10090:Zfp503 ^@ http://purl.uniprot.org/uniprot/Q7TMA2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Elbow/Noc family.|||May function as a transcriptional repressor.|||Nucleus http://togogenome.org/gene/10090:Emc8 ^@ http://purl.uniprot.org/uniprot/O70378|||http://purl.uniprot.org/uniprot/Q3TPU5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC8/EMC9 family.|||Component of the ER membrane protein complex (EMC). EMC8 and EMC9 are mutually exclusive subunits of the EMC complex.|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Ak6 ^@ http://purl.uniprot.org/uniprot/Q8VCP8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ AK6 and TAF9 were initially considered as products of the same gene since they share two exons. However, they are translated from different initiation codons and reading frames and encode unrelated proteins. This arrangement is conserved in some mammalian species.|||Belongs to the adenylate kinase family. AK6 subfamily.|||Broad-specificity nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. May have a role in nuclear energy homeostasis. Has also ATPase activity. May be involved in regulation of Cajal body (CB) formation.|||Cajal body|||Monomer and homodimer. Interacts with COIL (via C-terminus).|||nucleoplasm http://togogenome.org/gene/10090:Calcb ^@ http://purl.uniprot.org/uniprot/Q3UW96 ^@ Similarity ^@ Belongs to the calcitonin family. http://togogenome.org/gene/10090:Wdr73 ^@ http://purl.uniprot.org/uniprot/Q9CWR1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat WDR73 family.|||Cleavage furrow|||May play a role in the regulation of microtubule organization and dynamics.|||cytosol|||spindle|||spindle pole http://togogenome.org/gene/10090:Errfi1 ^@ http://purl.uniprot.org/uniprot/Q3TK48|||http://purl.uniprot.org/uniprot/Q99JZ7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MIG6 family.|||Cell membrane|||Cytoplasm|||Detected at low levels during embryogenesis. Strongly up-regulated during the first days after birth. Levels are increased on the first day after birth, and culminate three days after birth. Detected at low levels four days after birth, and throughout the remaining life span.|||Detected in lung, in airway epithelial cells and alveolar type 2 cells (at protein level). Detected in uterus stroma, luminal epithelium and glandular epithelium.|||Embryos are present at the expected Mendelian ratio, but half of the mice die before adolescence, due to defects in prenatal and perinatal lung development. In the 15.5 dpc embryo, lungs are smaller, have a less complex structure than normal, and present fewer blood vessels. Lungs in newborns present abnormal patterns of cell proliferation and apoptosis. Adults develop chronic obstructive pulmonary disease (COPD). Mice present epidermal hyperplasia with thickening and flaking skin and ulcerations on tail and footpads. Papillomas develop at sites of wounding. Mice are highly susceptible to chemical carcinogens and develop melanomas and/or papillomas after application of a carcinogen. They have a high incidence of spontaneous hyperplastic and neoplastic lesions, such as adenocarcinomas or squamous cell carcinomas. They present bone and cartilage hyperplasia, leading to fixed joints. Mice have altered response to progesterone in the uterus, resulting in endometrial epithelial hyperplasia and complete loss of fertility. Mice have a shortened life span and die prematurely at an age of five to seven months.|||Interacts with EGFR (By similarity). Interacts with ERBB2.|||Membrane|||Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development.|||Nucleus|||The EGFR-binding region prevents binding of a cyclin-like activator to the EGFR kinase domain, and thereby keeps EGFR in an inactive conformation. Also maintains EGFR in an inactive conformation by preventing formation of an asymmetric homodimer (By similarity).|||Up-regulated by lysophosphatidic acid (LPA) and sphingosine 1-phosphate. Up-regulated by globular actin monomers, via MKL1 signaling. Up-regulated in uterus in response to progesterone. Up-regulated in uterus in response to estrogen. Up-regulated in pregnant uterus. http://togogenome.org/gene/10090:Zzef1 ^@ http://purl.uniprot.org/uniprot/Q5SSH7 ^@ Function|||Subunit ^@ Histone H3 reader which may act as a transcriptional coactivator for KLF6 and KLF9 transcription factors.|||Interacts with KLF6 and KLF9 (By similarity). Interacts via (ZZ-type 2 zinc finger) with histone H3 trimethylated at 'Lys-4' (H3K4me3) and histone H3 acetylated at 'Lys-4' (H3K4ac) (By similarity). http://togogenome.org/gene/10090:Knstrn ^@ http://purl.uniprot.org/uniprot/Q9D9Z1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase. Promotes the metaphase-to-anaphase transition and is required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture. The astrin (SPAG5)-kinastrin (SKAP) complex promotes stable microtubule-kinetochore attachments. Required for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis, possibly by forming a link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division.|||Nucleus|||Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2 (By similarity). Interacts with SPAG5 (By similarity). Directly binds to microtubules, although at relatively low affinity (By similarity). Interacts with CENPE; this interaction greatly favors microtubule-binding (By similarity). Interacts with DSN1/MIS13; leading to localization to kinetochores (By similarity). Interacts with MAPRE1/EB1; leading to localization to the microtubule plus ends (By similarity). Interacts with PRPF19 (By similarity). Interacts with DYNLL1 (By similarity). Interacts with MAP4 (By similarity).|||The coiled coil regions mediate binding to kinetochores.|||kinetochore|||microtubule organizing center|||spindle pole http://togogenome.org/gene/10090:Cox6a2 ^@ http://purl.uniprot.org/uniprot/P43023 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase subunit 6A family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. Plays a role in the assembly and stabilization of complex IV (PubMed:31155743).|||Knockout mice show significant decline of COX activity and assembly in skeletal muscle. In particular, complexes IV, IV(2) and III(2)IV(2), and supercomplex I(1)III(2)IV(1) are reduced, whereas levels of complexes I, II, and III are normal.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Spopl ^@ http://purl.uniprot.org/uniprot/Q2M2N2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tdpoz family.|||Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, but with relatively low efficiency. Cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL are less efficient than ubiquitin ligase complexes containing only SPOP. May function to down-regulate the activity of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain SPOP (By similarity).|||Homodimer. Heterodimer with SPOP. Component of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL. Interacts with CUL3 and MACROH2A1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Slc16a12 ^@ http://purl.uniprot.org/uniprot/Q8BGC3 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Creatine uptake is inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and by valinomycin.|||Expressed in lens at P1 and P7 (PubMed:21778275). The expression levels are higher than in adult lens (PubMed:21778275). Detected in the basolateral membrane of the lens epithelium, with strong staining at equatorial epithelium, and in differentiating secondary fiber cells at P1 (at protein level) (PubMed:21778275).|||Functions as a transporter for creatine and as well for its precursor guanidinoacetate. Transport of creatine and GAA is independent of resting membrane potential and extracellular Na(+), Cl(-), or pH. Contributes to the process of creatine biosynthesis and distribution.|||Highly expressed in the lung, liver, kidney, and pancreas (PubMed:26376857). Expressed in eye lens.|||Interacts with isoform 2 of BSG; this interaction is required for its localization to the plasma membrane. http://togogenome.org/gene/10090:Tmc3 ^@ http://purl.uniprot.org/uniprot/E9Q6Y0|||http://purl.uniprot.org/uniprot/F8VQI4|||http://purl.uniprot.org/uniprot/Q7TQ69 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMC family.|||Detected in most neuronal organs and also in some non-neuronal tissues.|||Membrane|||Probable ion channel. http://togogenome.org/gene/10090:Med23 ^@ http://purl.uniprot.org/uniprot/E9QNV2|||http://purl.uniprot.org/uniprot/F8WJB0|||http://purl.uniprot.org/uniprot/Q80YQ2 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 23 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors (By similarity). Also required for transcriptional activation subsequent to the assembly of the pre-initiation complex. Required for transcriptional activation by adenovirus E1A protein. Required for ELK1-dependent transcriptional activation in response to activated Ras signaling.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CEBPB (when not methylated), CTNNB1, and GLI3. Interacts with CDK8 and ELK1.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus http://togogenome.org/gene/10090:Npw ^@ http://purl.uniprot.org/uniprot/F7B5D6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the neuropeptide B/W family.|||Secreted http://togogenome.org/gene/10090:Fbxo46 ^@ http://purl.uniprot.org/uniprot/Q8BG80 ^@ Function|||Subunit ^@ Interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Dennd2b ^@ http://purl.uniprot.org/uniprot/Q924W7 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form.|||Interacts with ITSN1 and GRB2. Isoform 1 interacts with the SH3 domain of ABL1.|||May be involved in cytoskeletal organization and tumorogenicity. Seems to be involved in a signaling transduction pathway leading to activation of MAPK1/ERK2. Plays a role in EGFR trafficking from recycling endosomes back to the cell membrane.|||May be produced by alternative promoter usage. Alternative promoter usage has been proven in human.|||May block ERK2 activation stimulated by ABL1. May alter cell morphology and cell growth.|||Phosphorylated. Phosphorylation decreases ITSN1 binding.|||Produced by alternative splicing of isoform 1.|||Recycling endosome|||cell cortex http://togogenome.org/gene/10090:Adcyap1 ^@ http://purl.uniprot.org/uniprot/O70176|||http://purl.uniprot.org/uniprot/Q3UYH8|||http://purl.uniprot.org/uniprot/Q8BJT8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glucagon family.|||Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells (By similarity). Promotes neuron projection development through the RAPGEF2/Rap1/B-Raf/ERK pathway (By similarity). In chromaffin cells, induces long-lasting increase of intracellular calcium concentrations and neuroendocrine secretion (By similarity). Involved in the control of glucose homeostasis, induces insulin secretion by pancreatic beta cells (PubMed:23913443).|||Interacts with ADCYAP1R1 (via N-terminal extracellular domain).|||Secreted http://togogenome.org/gene/10090:Efhb ^@ http://purl.uniprot.org/uniprot/Q8CDU5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Cytosolic sensor for calcium, modulates the interaction of STIM1 and ORAI1 upon store depletion and the activation of store-operated Ca(2+) entry (SOCE) and NFAT translocation from cytosol to nucleus (By similarity). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity).|||Interacts with STIM1 and ORAI1; the interactions take place upon Ca(2+)-store depletion and dissociate through a Ca(2+)-dependent mechanism. Interaction with STIM1 inhibits STIM1 interaction with SARAF.|||cilium axoneme http://togogenome.org/gene/10090:Ak3 ^@ http://purl.uniprot.org/uniprot/Q9WTP7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylate kinase family. AK3 subfamily.|||Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP hydrolysis.|||Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities.|||Mitochondrion matrix|||Monomer. http://togogenome.org/gene/10090:Sec13 ^@ http://purl.uniprot.org/uniprot/Q9D1M0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as a E3 ubiquitin-protein ligase toward GATOR1. In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex. Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex.|||At the nuclear pore: component of the Y-shaped Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13. At the COPII coat complex: interacts with SEC31A and SEC31B. Interacts with SEC16A. Interacts with SEC16B. Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids.|||Belongs to the WD repeat SEC13 family.|||COPII-coated vesicle membrane|||Endoplasmic reticulum membrane|||Functions as a component of the nuclear pore complex (NPC) and the COPII coat (By similarity). At the endoplasmic reticulum, SEC13 is involved in the biogenesis of COPII-coated vesicles. Required for the exit of adipsin (CFD/ADN), an adipocyte-secreted protein from the endoplasmic reticulum (PubMed:27354378).|||Lysosome membrane|||The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.|||nuclear pore complex http://togogenome.org/gene/10090:Cpne3 ^@ http://purl.uniprot.org/uniprot/Q8BT60 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the copine family.|||Calcium-dependent phospholipid-binding protein that plays a role in ERBB2-mediated tumor cell migration in response to growth factor heregulin stimulation.|||Cell junction|||Cell membrane|||Cytoplasm|||Monomer. Interacts with ERBB2 (preferentially with the tyrosine phosphorylated form); this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner. Interacts with SHC1; this interaction may mediate the binding of CPNE3 with ERBB2. Interacts with RACK1.|||Nucleus|||Phosphorylated on serine and threonine residues.|||focal adhesion http://togogenome.org/gene/10090:Tubal3 ^@ http://purl.uniprot.org/uniprot/Q3UX10 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (By similarity). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (By similarity).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility.|||The MREC motif may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Cep44 ^@ http://purl.uniprot.org/uniprot/Q5HZK1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Centriole-enriched microtubule-binding protein involved in centriole biogenesis. In collaboration with CEP295 and POC1B, is required for the centriole-to-centrosome conversion by ensuring the formation of bona fide centriole wall. Functions as a linker component that maintains centrosome cohesion. Associates with CROCC and regulates its stability and localization to the centrosome.|||Interacts with CROCC. Interacts with POC1B; the interaction is direct and recruits POC1B to centriolar microtubules. Binds to centriolar microtubules.|||Midbody|||centriole|||centrosome|||spindle pole http://togogenome.org/gene/10090:Dsg4 ^@ http://purl.uniprot.org/uniprot/Q7TMD7 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Coordinates the transition from proliferation to differentiation in hair follicle keratinocytes.|||Defects in Dsg4 are the cause of an autosomal recessive phenotype lanceolate hair (lah). Lah mice pups develop only a few short hairs on the head and neck which form a lance head at the tip and disappear within a few month. They have thickened skin and do not exhibit any growth retardation.|||Expressed in embryo at 7 to 17 dpc.|||Strongly expressed in the skin; during the anagen stage of hair follicles in the matrix, precortex and inner rooth sheath.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Myo5c ^@ http://purl.uniprot.org/uniprot/E9Q1F5 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Adgrg5 ^@ http://purl.uniprot.org/uniprot/Q3V3Z3 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adhesion G protein-coupled receptor (GPCR). Transduces intracellular signals through coupling to guanine nucleotide-binding protein G(s) subunit alpha and activation of adenylate cyclase pathway (PubMed:22575658). Isoform 1, but not isoform 2, is constitutively active, as evidenced by elevated basal cAMP levels, and responds to mechanical activation (shaking) (PubMed:26499266).|||Autoproteolysis between residues Leu-222 and Thr-223 occurs in the lumen of the endoplasmic reticulum during receptor biosynthesis. The N-terminal fragment (NTF) subsequently reassociates with the C-terminal fragment (CTF) either in a homogeneric heterodimerization, or with another family member through heterogeneric heterodimerization. Autocatalytic cleavage is thought to be critical for the maturation, stability, trafficking, and function.|||Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Expressed at least in kidney, heart, brain and spleen. In the kidney, both isoform 1 and isoform 2 are expressed at similar levels. Isoform 1 is predominant in spleen, while isoform 2 is the major form in heart and brain.|||May be due to competing acceptor splice site. http://togogenome.org/gene/10090:Prox2 ^@ http://purl.uniprot.org/uniprot/Q8BII1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Prospero homeodomain family.|||Expressed in testis.|||Expressed in the developing nervous system. Expressed at 9.5 dpc in the geniculate (VIIth), petrosal (IXth), and nodose (Xth) ganglia. Expressed in postnatal eyes.|||Mice grow normally and body weight was similar to that of wild type. Heterozygous mutant mice survived to adulthood and appeared normal.|||Nucleus|||The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain.|||Transcription regulator. Does not seem to be essential for embryonic development and postnatal survival. http://togogenome.org/gene/10090:Or8g18 ^@ http://purl.uniprot.org/uniprot/P34983 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Tgtp1 ^@ http://purl.uniprot.org/uniprot/Q3T9E4|||http://purl.uniprot.org/uniprot/Q62293 ^@ Caution|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in thymus and lymph nodes, predominantly T-cells. Not expressed by immature CD4(+) CD8(+) thymocytes (at protein level) (PubMed:7836757). Expressed in IFNG-stimulated macrophages (PubMed:7884320). Expressed at low levels in unstimulated astrocytes (PubMed:19285957). Due to sequence similarity with Tgtp1, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene.|||Expressed in thymus and lymph nodes, predominantly T-cells. Not expressed by immature CD4(+) CD8(+) thymocytes (at protein level) (PubMed:7836757). Expressed in IFNG-stimulated macrophages (PubMed:7884320). Expressed at low levels in unstimulated astrocytes (PubMed:19285957). Due to sequence similarity with Tgtp2, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene.|||Golgi apparatus|||In macrophages, up-regulated by IFNG, but not by IL2, IL4, IL10, nor TNF (PubMed:7884320). Up-regulated by IFNG in lymph node cells and thymocytes and other cell types (PubMed:7836757, PubMed:9725230, PubMed:24563254). In astrocytes, up-regulated by TNF and IFNG; when both cytokines are combined, the effect is synergistic (PubMed:19285957). Due to sequence similarity with Tgtp1, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene (Probable).|||In macrophages, up-regulated by IFNG, but not by IL2, IL4, IL10, nor TNF (PubMed:7884320). Up-regulated by IFNG in lymph node cells and thymocytes and other cell types (PubMed:7836757, PubMed:9725230, PubMed:24563254). In astrocytes, up-regulated by TNF and IFNG; when both cytokines are combined, the effect is synergistic (PubMed:19285957). Due to sequence similarity with Tgtp2, it is impossible to assign unambiguously experimental data published in the literature to Tgtp1 or Tgtp2 gene (Probable).|||Involved in innate cell-autonomous resistance to intracellular pathogens, such as Toxoplasma gondii (PubMed:19265156, PubMed:20109161, PubMed:24563254). During avirulent type II T. gondii infection, recruited to the parasitophorous vacuole (PV) membrane, leading to PV vesiculation and rupture, and subsequent digestion of the parasite within the cytosol (PubMed:19265156, PubMed:24563254). Not recruited to virulent type I T. gondii PV membrane (PubMed:19265156). May confer an antiviral state for vesicular stomatitis virus (PubMed:9725230).|||The gene Tgtp1 belongs to a large family of eutherian IFNG-inducible GTPases, called immunity-related p47 GTPases, which comprises a variable amount of paralogs depending upon the species studied. In C57BL/6J mice, there is over 20 genes, whereas humans have only one ortholog. Tgtp1 closest paralog is Tgtp2. Both genes encode identical proteins. At the nucleotide sequence level, their CDSs differ at only 4 positions. Consequently it is almost impossible to assign unambiguously to one gene or the other experimental data published in the literature.|||The gene Tgtp1 belongs to a large family of eutherian IFNG-inducible GTPases, called immunity-related p47 GTPases, which comprises a variable amount of paralogs depending upon the species studied. In C57BL/6J mice, there is over 20 genes, whereas humans have only one ortholog. Tgtp2 closest paralog is Tgtp1. Both genes encode identical proteins. At the nucleotide sequence level, their CDSs differ at only 4 positions. Consequently it is almost impossible to assign unambiguously to one gene or the other experimental data published in the literature. http://togogenome.org/gene/10090:Ly86 ^@ http://purl.uniprot.org/uniprot/O88188 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in spleen, liver, brain and thymus, and at lower levels in kidney.|||M-shaped tetramer of two CD180-LY86 heterodimers.|||May cooperate with CD180 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and cytokine production. Important for efficient CD180 cell surface expression.|||extracellular space http://togogenome.org/gene/10090:Eva1b ^@ http://purl.uniprot.org/uniprot/Q8K2Y3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the EVA1 family.|||Membrane http://togogenome.org/gene/10090:Lrrc10 ^@ http://purl.uniprot.org/uniprot/Q8K3W2 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected specifically in the heart.|||May play important roles in cardiac development and/or cardiac function.|||Nucleus http://togogenome.org/gene/10090:Lgals9 ^@ http://purl.uniprot.org/uniprot/O08573 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accentuated expression in liver and thymus of embryo, detected in embryonic heart, brain, lung, liver, and kidney. Highly expressed in adult thymus, small intestine, and liver, and to a lesser extent in lung, kidney, spleen, cardiac, and skeletal muscle. Barely detectable in brain and reticulocyte. Expressed in placenta, uterus and decidua during pregnancy (PubMed:23242525). Expressed in CD4+ T-cells with higher levels in iTreg cells than other T-cell types and sustained high levels throughout iTreg cell differentiation (at protein level) (PubMed:25065622). Expressed in myeloid cells in lung (PubMed:20937702). Constitutively expressed in microglia (PubMed:25158758). Isoform 1 is expressed exclusively in the small intestine. Isoform 2 expression in decidua increases in pathological pregnancy from gestation day 7.5 to 13.5 and it is higher than in normal pregnancy (PubMed:23242525). Isoform 3 expression in decidua is higher in normal pregnancy than in pathological pregnancy (PubMed:23242525).|||Acts as an eosinophil chemoattractant (By similarity). It also inhibits angiogenesis (By similarity). Suppresses IFNG production by natural killer cells.|||Binds galactosides (By similarity). Has high affinity for the Forssman pentasaccharide (By similarity). Ligand for HAVCR2/TIM3 (By similarity). Binding to HAVCR2 induces T-helper type 1 lymphocyte (Th1) death (By similarity). Also stimulates bactericidal activity in infected macrophages by causing macrophage activation and IL1B secretion which restricts intracellular bacterial growth (PubMed:20937702). Ligand for P4HB; the interaction retains P4HB at the cell surface of Th2 T-helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). Ligand for CD44; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up-regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function (PubMed:25065622). Promotes ability of mesenchymal stromal cells to suppress T-cell proliferation (By similarity). Expands regulatory T-cells and induces cytotoxic T-cell apoptosis following virus infection (By similarity). Activates ERK1/2 phosphorylation inducing cytokine (IL-6, IL-8, IL-12) and chemokine (CCL2) production in mast and dendritic cells (By similarity). Inhibits degranulation and induces apoptosis of mast cells (By similarity). Induces maturation and migration of dendritic cells (By similarity). Inhibits natural killer (NK) cell function (PubMed:23408620). Can transform NK cell phenotype from peripheral to decidual during pregnancy (By similarity). Astrocyte derived galectin-9 enhances microglial TNF production (PubMed:25158758). May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. May provide the molecular basis for urate flux across cell membranes, allowing urate that is formed during purine metabolism to efflux from cells and serving as an electrogenic transporter that plays an important role in renal and gastrointestinal urate excretion (By similarity). Highly selective to the anion urate (By similarity).|||By viral mimic polyinosinic:polycytidylic acid (poly I:C) and lipopolysaccharides (LPS) in microglia (PubMed:25158758). Up-regulated in macrophages following infection with Mycobacterium tuberculosis (PubMed:20937702).|||Contains two homologous but distinct carbohydrate-binding domains.|||Cytoplasm|||Homodimer.|||Increased natural killer (NK) cell activity with enhanced degranulation, higher expression of NK cell activating receptors, increased frequency of intermediate and mature NK cells, and greater production of interferon-gamma following murine cytomegalovirus infection (PubMed:23408620). Defective iTreg cell differentiation with impaired Foxp3 expression, reduced stability and suppressor function of iTreg cells and reduced frequency of iTreg cells but not natural regulatory T (nTreg) cells in lamina propria (PubMed:25065622).|||Nucleus|||Secreted|||The expression increases with successive stages of embryonic development. http://togogenome.org/gene/10090:Tyrobp ^@ http://purl.uniprot.org/uniprot/O54885|||http://purl.uniprot.org/uniprot/Q3U419 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:15471863, PubMed:9647200). TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation (PubMed:15728241). Also has an inhibitory role in some cells (PubMed:21727189). Non-covalently associates with activating receptors of the CD300 family to mediate cell activation (By similarity). Also mediates cell activation through association with activating receptors of the CD200R family (PubMed:15471863). Required for neutrophil activation mediated by integrin (PubMed:17086186). Required for the activation of myeloid cells mediated by the CLEC5A/MDL1 receptor (By similarity). Associates with natural killer (NK) cell receptors such as the KLRD1/KLRC2 heterodimer to mediate NK cell activation (By similarity). Also associates non-covalently with the NK cell receptors KLRA4/LY49D and KLRA8/LY49H which leads to NK cell activation (PubMed:9647200). Associates with TREM1 to mediate activation of neutrophils and monocytes (By similarity). Associates with TREM2 on monocyte-derived dendritic cells to mediate up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (By similarity). Association with TREM2 mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (PubMed:18957693). Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) which is produced by TREM2 ectodomain shedding (By similarity). In microglia, required with TREM2 for phagocytosis of apoptotic neurons (PubMed:15728241). Required with ITGAM/CD11B in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (PubMed:18685038). Promotes pro-inflammatory responses in microglia following nerve injury which accelerates degeneration of injured neurons (PubMed:25690660). Positively regulates the expression of the IRAK3/IRAK-M kinase and IL10 production by liver dendritic cells and inhibits their T cell allostimulatory ability (PubMed:21257958). Negatively regulates B cell proliferation (PubMed:21727189). Required for CSF1-mediated osteoclast cytoskeletal organization (PubMed:18691974). Positively regulates multinucleation during osteoclast development (PubMed:12569157, PubMed:14969392).|||Belongs to the TYROBP family.|||Cell membrane|||Expressed on microglia (at protein level) (PubMed:12569157, PubMed:18685038). Expressed on oligodendrocytes (at protein level) (PubMed:12569157). Expressed on macrophages and osteoclasts (PubMed:14969392). Expressed on dendritic cells in liver, spleen, kidney and lung with highest levels in liver dendritic cells (PubMed:21257958).|||Homodimer; disulfide-linked (By similarity). Homotrimer; disulfide-linked (By similarity). Homotetramer; disulfide-linked (By similarity). Homotrimers and homotetramers form when low levels of partner receptors are available and are competitive with assembly with interacting receptors (By similarity). They may represent alternative oligomerization states or may be intermediates in the receptor assembly process (By similarity). Binding of a metal cation aids in homooligomerization through coordination of the metal ion by the subunits of the oligomer (By similarity). Interacts with TREM1 (By similarity). Interacts with TREM2 (PubMed:29518356). Interacts with TREM3 (PubMed:11754004). Interacts with CLECSF5 (PubMed:10449773). Interacts with CD300LB and CD300C2 (PubMed:12874256, PubMed:12893283, PubMed:17202337, PubMed:17928527). Interacts with CD300E (By similarity). Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophil and macrophage integrin-mediated activation (PubMed:17086186). Interacts (via transmembrane domain) with KLRK1 isoform 2 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and NK cell-mediated cytotoxicity (PubMed:12426564, PubMed:12426565, PubMed:15294961). Interacts with KLRC2 (By similarity). Interacts with CD300H (By similarity). Interacts with KLRD1 (By similarity). Interacts with KLRA4 and KLRA8 (PubMed:9647200).|||Increased bone mass and failure to generate multinuclear osteoclasts in vitro (PubMed:12569157, PubMed:14969392). Thalamic hypomyelination, synaptic degeneration, reduced startle response and aberrant electrophysiological profiles (PubMed:12569157). Enhanced proliferation of B cells (PubMed:21727189). Reduced number of microglia at sites of nerve injury and high rate of neuronal survival (PubMed:25690660). Impaired macrophage fusion (PubMed:18957693). Defective osteoclast cytoskeletal organization and function (PubMed:18691974).|||Induced in microglia following nerve injury (at protein level) (PubMed:25690660). Induced in liver dendritic cells by physiological concentrations of lipopolysaccharide (PubMed:21257958).|||Membrane|||Tyrosine phosphorylated (PubMed:11754004, PubMed:12426565, PubMed:15728241, PubMed:17086186, PubMed:18691974, PubMed:9490415, PubMed:9852069). Following ligand binding by associated receptors, tyrosine phosphorylated in the ITAM domain which leads to activation of additional tyrosine kinases and subsequent cell activation (By similarity). http://togogenome.org/gene/10090:Supt4b ^@ http://purl.uniprot.org/uniprot/Q9Z199 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SPT4 family.|||Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (By similarity).|||Expressed in brain, heart and liver.|||Interacts with SUPT5H to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of WHSC2/NELFA, COBRA1/NELFB, TH1L/NELFD and RDBP/NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with HRMT1L2/PRMT1, HTATSF1/TATSF1, RNGTT/CAP1A, SKB1/PRMT5, SUPT6H, and can interact with PIN1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Pcnx2 ^@ http://purl.uniprot.org/uniprot/Q5DU28 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pecanex family.|||May play a role in tumorigenesis.|||Membrane http://togogenome.org/gene/10090:Tmem259 ^@ http://purl.uniprot.org/uniprot/Q8CIV2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the membralin family.|||Detected in brain, spinal cord, lung, liver and kidney.|||Endoplasmic reticulum membrane|||Interacts with ERLIN2.|||Lethality typically occurs several days after birth, associated with motor neuron deficiency and paresis.|||May have a role in the ERAD pathway required for clearance of misfolded proteins in the endoplasmic reticulum (ER). Promotes survival of motor neurons, probably by protecting against ER stress. http://togogenome.org/gene/10090:Pfkfb1 ^@ http://purl.uniprot.org/uniprot/A2AFM9|||http://purl.uniprot.org/uniprot/P70266 ^@ Activity Regulation|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Homodimer.|||In the C-terminal section; belongs to the phosphoglycerate mutase family.|||Liver.|||Phosphorylation at Ser-33 inhibits the kinase and activates the bisphosphatase.|||Synthesis and degradation of fructose 2,6-bisphosphate. http://togogenome.org/gene/10090:Hmga2 ^@ http://purl.uniprot.org/uniprot/P52927|||http://purl.uniprot.org/uniprot/Q6NSP9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HMGA family.|||Expressed in mitotic spermatogonia, meiotic spermatocytes, and postmeiotic round spermatids (at protein level) (PubMed:14668482). Expressed in embryonic myogenic progenitor cells (PubMed:27446912).|||Expressed predominantly during embryogenesis. In myogenic progenitor cells, expressed during early myogenic development (11.5 dpc) to be gradually down-regulated during the fetal stages (17.5 dpc) (PubMed:27446912).|||Functions as a transcriptional regulator. Functions in cell cycle regulation through CCNA2. Plays an important role in chromosome condensation during the meiotic G2/M transition of spermatocytes. Plays a role in postnatal myogenesis, is involved in satellite cell activation (PubMed:27446912). Positively regulates IGF2 expression through PLAG1 and in a PLAG1-independent manner (By similarity).|||Interacts with E4F1 (By similarity). Interacts with NEK2 (PubMed:14668482).|||Nucleus|||Regulated by cell cycle-dependent phosphorylation which alters its DNA binding affinity. Phosphorylated by NEK2. http://togogenome.org/gene/10090:Arfgap2 ^@ http://purl.uniprot.org/uniprot/Q99K28 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). May regulate coatomer-mediated protein transport from the Golgi complex to the endoplasmic reticulum. Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes (By similarity).|||Golgi apparatus membrane|||High levels in mammary glands of virgin mice and in mammary glands of pregnant mice associated with extensive proliferation of ductal cells and lobulo-alveolar development. Expression declines at the beginning of lactation when the glands fully differentiate. No expression after day 2 of lactation until day 21. Expression may be controlled by ID1.|||Highly expressed in liver, heart and kidney. Low expression in skeletal muscle and spleen.|||Interacts with the coatomer complex. Interacts with the C-terminal appendage domain of COPG1 (By similarity). http://togogenome.org/gene/10090:Rhcg ^@ http://purl.uniprot.org/uniprot/Q9QXP0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Ammonium transporter involved in the maintenance of acid-base homeostasis. Transports ammonium and its related derivative methylammonium across the plasma membrane of epithelial cells likely contributing to renal transepithelial ammonia transport and ammonia metabolism. Postulated to primarily mediate an electroneutral bidirectional transport of NH3 ammonia species according to a mechanism that implies interaction of an NH4(+) ion with acidic residues of the pore entry followed by dissociation of NH4(+) into NH3 and H(+). As a result NH3 transits through the central pore and is protonated on the extracellular side reforming NH4(+) (PubMed:16131648) (By similarity). May act as a CO2 channel providing for renal acid secretion (By similarity).|||Apical cell membrane|||Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.|||Expressed in the forestomach and the fundus of the stomach. Expressed at the level of villous in duodenum, jejunum, ileum and colon. Expressed in kidney by connecting segments and collecting tubules (at protein level). Expressed in testis by seminiferous tubules.|||Homotrimer.|||N-glycosylated. http://togogenome.org/gene/10090:Necab1 ^@ http://purl.uniprot.org/uniprot/Q8BG18 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain (at protein level). Expressed in the cerebral cortex only in layer 4, thalamic nuclei (the mediodorsal nucleus), hippocampus (a small band of pyramidal neurons at the boundary between CA1 and CA3), interneurons interspersed throughout the hippocampus proper, interneurons in the hilus, bodies of the neurons but also their dendritic projections (at protein level).|||Interacts with STX1. May interact with CPNE6. http://togogenome.org/gene/10090:Or8d4 ^@ http://purl.uniprot.org/uniprot/Q8VGB4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Uxs1 ^@ http://purl.uniprot.org/uniprot/Q91XL3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family. UDP-glucuronic acid decarboxylase subfamily.|||Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose. Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis.|||Golgi stack membrane|||Homodimer and homotetramer (By similarity). Interacts with AKT1 (By similarity). http://togogenome.org/gene/10090:Eml4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0H0|||http://purl.uniprot.org/uniprot/A0A0R4J1G7|||http://purl.uniprot.org/uniprot/A0A3Q4EHV9|||http://purl.uniprot.org/uniprot/A7ISP9|||http://purl.uniprot.org/uniprot/F8WJ93|||http://purl.uniprot.org/uniprot/Q3UMY5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat EMAP family.|||Cytoplasm|||Essential for the stability of microtubules (MTs) (PubMed:17196341). Essential for the formation of MTs (By similarity). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs (By similarity). Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression (By similarity).|||Homotrimer; self-association is mediated by the N-terminal coiled coil (By similarity). Interacts (via WD repeats) with NUDC (By similarity). Interacts with alpha- and beta-tubulin during mitosis (By similarity).|||Midbody|||Phosphorylated during mitosis (By similarity). Phosphorylation at Ser-144 and Ser-146 promotes its dissociation from microtubules during mitosis which is required for efficient chromosome congression (By similarity).|||cytoskeleton|||microtubule organizing center|||spindle http://togogenome.org/gene/10090:Cilp2 ^@ http://purl.uniprot.org/uniprot/D3Z7H8 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in articulated and meniscal cartilage (at protein level). Also detected in heart, skeletal muscle and brain. Not detected in growth plate cartilage.|||In the knee joint, detected in articular cartilage from 2 weeks of age but not at earlier stages (at protein level). Initially localizes to the surface zone of articular cartilage but by maturity (8 weeks) is found in the intermediate to deep zones (at protein level).|||May be cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.|||May play a role in cartilage scaffolding.|||N-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Tmem81 ^@ http://purl.uniprot.org/uniprot/Q9D5K1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Sprr2i ^@ http://purl.uniprot.org/uniprot/O70560 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cornifin (SPRR) family.|||Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane (By similarity).|||Cytoplasm|||Not expressed in uterus. http://togogenome.org/gene/10090:Or10ag58 ^@ http://purl.uniprot.org/uniprot/A2AT86 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Laptm5 ^@ http://purl.uniprot.org/uniprot/Q544S4|||http://purl.uniprot.org/uniprot/Q61168 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LAPTM4/LAPTM5 transporter family.|||Binds to ubiquitin.|||By retinoic acid. Likely target of the activated retinoic acid receptor alpha.|||During embryonic development it is expressed in both hematopoietic and nonhematopoietic tissues.|||Lysosome membrane|||May have a special functional role during embryogenesis and in adult hematopoietic cells.|||Preferentially expressed in adult hematopoietic tissues. High levels in lymphoid and myeloid tissues. http://togogenome.org/gene/10090:Cfap126 ^@ http://purl.uniprot.org/uniprot/Q6P8X9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the Flattop family.|||Expressed in mono- and multiciliated tissues during planar cell polarity acquisition.|||First detected in the embryonic node at 7.5 dpc. At 8.5-13.5 dpc, strong expression is detected in tissues that are either mono- or multiciliated, such as the eye, notochord, floor plate of the neural tube and all 4 choroid plexi. Expressed during development and early postnatal life in all 6 sensory regions of the inner ear.|||Interacts with DLG3.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme (By similarity). Acts as a regulator of cilium basal body docking and positioning in mono- and multiciliated cells. Regulates basal body docking and cilia formation in multiciliated lung cells. Regulates kinocilium positioning and stereocilia bundle morphogenesis in the inner ear.|||cilium axoneme|||cilium basal body|||mice were born at the expected Mendelian ratio and are viable and fertile but show basal body docking and ciliogenesis defects in multiciliated lung cells. http://togogenome.org/gene/10090:Plekha7 ^@ http://purl.uniprot.org/uniprot/Q3UIL6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in kidney and lung (at protein level).|||Interacts with CAMSAP3 and CTNND1 (By similarity). Interacts (via WW domains) with TSPAN33 (via cytoplasmic domain) and with PDZD11; the interaction with TSPAN33 is dependent on PDZD11 being bound to PLEKHA7 and facilitates the docking of ADAM10 to zonula adherens through interaction of TSPAN33 with ADAM10 (PubMed:30463011).|||Required for zonula adherens biogenesis and maintenance. Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site (By similarity). Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33 (PubMed:30463011).|||adherens junction|||centrosome http://togogenome.org/gene/10090:Cdh22 ^@ http://purl.uniprot.org/uniprot/Q9WTP5 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. PB-cadherins may have a role in the morphological organization of pituitary gland and brain tissues.|||Cell membrane|||Down-regulated by thyroid hormone.|||Expressed at 9.5 dpc onwards. At 10.5 dpc, in brain (telencephalic vesicles and isthmus), spinal cord and limb buds (in the zone of polarizing activity). At 14.5 dpc, in olfactory bulb and cerebellum.|||Predominantly expressed in brain. Abundant in olfactory bulb, cerebrum, and cerebellum, less in pons, medulla, and spinal cord. Low expression in heart. No expression in lung, liver, spleen, kidney, testis, stomach, intestine, colon, and placenta.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Stra8 ^@ http://purl.uniprot.org/uniprot/P70278 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed exclusively in premeiotic germ cells in both sexes. In females, is expressed in the embryonic ovary. In males, is expressed in pubertal and adult testes, in premeiotic spermatogenic cells. Expressed by some type A and B spermatogonia, preleptotene spermatocytes, and early leptotene spermatocytes (at protein level). Expression begins in late undifferentiated spermatogonia and persists during differentiating spermatogonia (at protein level).|||Female and male mice are infertile due to severe gametogenesis impairment. In female mutant embryos, the initial mitotic development of germ cells is normal, but they fail to undergo promeiotic DNA replication and meiotic chromosome condensation. In male mutants, the premeiotic DNA replication is conserved and germ cells are able to partly condense chromosomes and initiate meiotic recombination. However, they fail to regularily continue over the leptotene stage of prophase I.|||Interacts with XPO1. Interacts with MEIOSIN (PubMed:32032549).|||Meiosis-inducer required for the transition into meiosis for both female and male germ cells (PubMed:16461896, PubMed:17115059, PubMed:18799751, PubMed:18799790, PubMed:19805549, PubMed:32054698, PubMed:32032549). In female germ cells, acts downstream of ZGLP1 as a key effector of the meiotic program: required for premeiotic DNA replication and subsequent events in meiotic prophase (PubMed:16461896, PubMed:17115059, PubMed:18799751, PubMed:18799790, PubMed:32054698). During spermatogenesis, next to its role in meiotic initiation, promotes (but is not required for) spermatogonial differentiation (PubMed:25902548). In complex with MEIOSIN, directly activates the transcription of a subset of critical meiotic genes playing a central role in cell-cycle switching from mitosis to meiosis (PubMed:19805549, PubMed:32032549).|||Nucleus|||Phosphorylated in P19 EC cells.|||Up-regulated by retinoic acid in embryonic ovaries and adult testes, and by all-trans and 9-cis retinoic acid in P19 embryonic carcinoma (EC) cells. Transcription is repressed by DMRT1 in undifferentiated spermatogonia.|||Up-regulated in embryonic germ cells of the female gonads in an anterior-to-posterior wave from 12.5 dpc to 16.5 dpc. In male gonads, expression is first detected after birth. http://togogenome.org/gene/10090:Fam98c ^@ http://purl.uniprot.org/uniprot/E9PYD1 ^@ Similarity ^@ Belongs to the FAM98 family. http://togogenome.org/gene/10090:Cfhr1 ^@ http://purl.uniprot.org/uniprot/Q61406 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Nrarp ^@ http://purl.uniprot.org/uniprot/Q91ZA8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Axial skeletal defects in newborn mice such as rib fusions, fused vertebral bodies and fused pedicles of the vertebrae; defects are influenced by the strain-specific genetic background. Embryos exhibit expansion and fusion of myotomes, dorsal root ganglia fusions and defects in projection of the spinal nerves. Embryos show increased level of Notch 1 intracellular domain (NICD) expression in presomitic mesoderm and somites (PubMed:21998026). In contrast, fewer somites and vertebrae found in -/- are linked to a longer segmentation clock period (PubMed:21795391). Defects in the radial expansion of the vascular plexus from the optic nerve head to the periphery, reduction of retinal vessel density; however, most of the defects in angiogenesis resolve over time (PubMed:19154719).|||Belongs to the NRARP family.|||By Notch signaling via a CBF1/Su(H)/Lag-1 (CSL)-dependent pathway.|||Downstream effector of Notch signaling. Involved in the regulation of liver cancer cells self-renewal (By similarity). Involved in the regulation of canonical Wnt signaling by stabilizing LEF1 (By similarity). Involved in angiogenesis acting downstream of Notch at branch points to regulate vascular density. Proposed to integrate endothelial Notch and Wnt signaling to control stalk cell proliferation and to stablilize new endothelial connections during angiogenesis (PubMed:19154719). During somitogenesis involved in maintenance of proper somite segmentation and proper numbers of somites and vertebrae. Required for proper anterior-posterior somite patterning. Proposed to function in a negative feedback loop to destabilize Notch 1 intracellular domain (NICD) and down-regulate the Notch signal, preventing expansion of the Notch signal into the anterior somite domain (PubMed:21795391, PubMed:21998026).|||During embryogenesis, expressed in several tissues in which cellular differentiation is regulated by the notch signaling pathway. At 10.5 dpc expressed in intersomatic vessels and in vessels of the limb buds with strongest expression at vascular branch points. Cyclic expression between 8.5 dpc and 10.5 dpc somitogenesis is dependent on DLL3.|||Expressed at high levels in the brain, heart, colon, kidney, liver, lung and small intestine. Expressed in retina, most prominent in endothelial cells at the migrating point of the vasculature behind leading tip cells. Expressed in testis.|||Interacts with LEF1. http://togogenome.org/gene/10090:Arf1 ^@ http://purl.uniprot.org/uniprot/P84078 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alternates between an inactive GDP-bound form and an active GTP-bound form (By similarity). Activated by guanine nucleotide-exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs) (By similarity).|||Belongs to the small GTPase superfamily. Arf family.|||Golgi apparatus membrane|||Interacts (when activated) with GGA1, GGA2 and GGA3; the interaction is required for proper subcellular location of GGA1, GGA2 and GGA3 (PubMed:11950392, PubMed:12679809). Interacts with ARHGAP21, ASAP2, HERC1, PRKCABP, PIP5K1B, TMED2, PSCD2, TMED10 and GRIA2 (PubMed:17347647). Interacts with ARFGAP1, which hydrolyzes GTP and thus, regulates its function. Interacts with PI4KB in the Golgi complex. Interacts with NCS1/FREQ in the Golgi and at the plasma membrane. Interacts with PLEKHA3. Interacts with PLEKHA8; the interaction, together with phosphatidylinositol 4-phosphate binding, is required for FAPP2-mediated glucosylceramide transfer activity. Interacts (activated) with PICK1 (via PDZ domain); the interaction blocks Arp2/3 complex inhibition. Interacts with IQSEC1 (By similarity). Interacts with C9orf72 (PubMed:27723745) (By similarity).|||Postsynaptic density|||Small GTPase involved in protein trafficking between different compartments (PubMed:11950392). Modulates vesicle budding and uncoating within the Golgi complex (By similarity). In its GTP-bound form, triggers the recruitment of coatomer proteins to the Golgi membrane (By similarity). The hydrolysis of ARF1-bound GTP, which is mediated by ARFGAPs proteins, is required for dissociation of coat proteins from Golgi membranes and vesicles (By similarity). The GTP-bound form interacts with PICK1 to limit PICK1-mediated inhibition of Arp2/3 complex activity; the function is linked to AMPA receptor (AMPAR) trafficking, regulation of synaptic plasticity of excitatory synapses and spine shrinkage during long-term depression (LTD) (By similarity).|||synaptosome http://togogenome.org/gene/10090:Nlrp4b ^@ http://purl.uniprot.org/uniprot/Q8C6J9 ^@ Function|||Similarity ^@ Belongs to the NLRP family.|||May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. http://togogenome.org/gene/10090:Dennd10 ^@ http://purl.uniprot.org/uniprot/Q3TH34|||http://purl.uniprot.org/uniprot/Q9D8N2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DENND10 family.|||Endosome|||Guanine nucleotide exchange factor (GEF) regulating homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as RAB27A and RAB27B. Seems to promote the exchange of GDP to GTP, converting inactive GDP-bound RAB27A and RAB27B into their active GTP-bound form.|||Interacts with RAB27A and RAB27B (GDP-bound forms preferentially).|||Late endosome http://togogenome.org/gene/10090:Klc2 ^@ http://purl.uniprot.org/uniprot/Q91YS4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the kinesin light chain family.|||Kinesin is a microtubule-associated force-producing protein that play a role in organelle transport.|||Oligomeric complex composed of two heavy chains and two light chains.|||cytoskeleton http://togogenome.org/gene/10090:Dlgap2 ^@ http://purl.uniprot.org/uniprot/Q0VF59|||http://purl.uniprot.org/uniprot/Q3V2X4|||http://purl.uniprot.org/uniprot/Q8BJ42 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SAPAP family.|||Cell membrane|||Expressed in various brain areas.|||Interacts with DLG4/PSD-95.|||May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/SAP90 at the plasma membrane.|||Postsynaptic density|||Synapse http://togogenome.org/gene/10090:Dbp ^@ http://purl.uniprot.org/uniprot/Q3USN7|||http://purl.uniprot.org/uniprot/Q60925 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates according to a robust circadian rhythm in liver and kidney. In liver nuclei, the amplitude of daily oscillation has been estimated to be >50-fold, and 2-fold in the brain.|||Belongs to the bZIP family. PAR subfamily.|||Binds DNA as a homodimer or a heterodimer. Can form a heterodimer with TEF (By similarity).|||Expressed in the suprachiasmatic nuclei (SCN) and in most peripheral tissues, with a strong circadian rhythmicity.|||Mice deficient for all three PAR bZIP proteins (DBP, HLF and TEF) display a dramatically shortened life span and are highly susceptible to generalized spontaneous and audiogenic epilepsies (due for example to the noise of a vacuum cleaner) that are frequently lethal. The down-regulation of pyridoxal kinase (Pdxk) expression in these mice may participate in this seizure phenotype.|||Nucleus|||This transcriptional activator recognizes and binds to the sequence 5'-RTTAYGTAAY-3' found in the promoter of genes such as albumin, CYP2A4 and CYP2A5. It is not essential for circadian rhythm generation, but modulates important clock output genes. May be a direct target for regulation by the circadian pacemaker component clock. May affect circadian period and sleep regulation (By similarity). http://togogenome.org/gene/10090:Neurl2 ^@ http://purl.uniprot.org/uniprot/A2A5J5 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Iws1 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLV0|||http://purl.uniprot.org/uniprot/Q8C1D8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IWS1 family.|||Interacts with SUPT6H; binds preferentially to the POLR2A-bound SUPT6H. Interacts with ALYREF/THOC4, SETD2 and PRMT5 (By similarity). Interacts with HDGFRP2 (By similarity). Interacts (via IBM motif) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (By similarity).|||Nucleus|||Phosphorylation increases its interaction with PSIP1.|||Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription (By similarity).|||Ubiquitous. Expressed at highest level in kidney, then testicle, large intestine, small intestine, spleen and prostate, whereas the lowest level is detected in heart. http://togogenome.org/gene/10090:Upk3bl ^@ http://purl.uniprot.org/uniprot/Q9D701 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the uroplakin-3 family.|||Membrane http://togogenome.org/gene/10090:Bnc2 ^@ http://purl.uniprot.org/uniprot/Q8BMQ3 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Detected at embryonic days 15.5 and 17.5. Expressed in the developing lower urinary-tract structures, with emphasis on the genital tubercle above the phallic urethra and below the pelvic urethra at as early as embryonic day 13.5 dpc, the critical time point for urethral development. In embryos, expression is also visible in the brain, in the mandibular region, and in dorsal parts above the spinal cord.|||Highly expressed in ovary, testis and kidney. Expressed at moderate levels in skin and small intestine, and at lower levels in lung. Trace amounts of expression detected in liver and colon. Not detected in brain, spleen or thymus.|||Nucleus|||Probable transcription factor specific for skin keratinocytes. May play a role in the differentiation of spermatozoa and oocytes. May also play an important role in early urinary-tract development. http://togogenome.org/gene/10090:Dmrtc1a ^@ http://purl.uniprot.org/uniprot/B1AX34|||http://purl.uniprot.org/uniprot/Q9D9R7 ^@ Caution|||Developmental Stage|||Similarity|||Tissue Specificity ^@ Although related to other DMRT proteins, it does not contain a canonical DM DNA-binding domain.|||Belongs to the DMRT family.|||Detected in many tissues at 13.5 dpc.|||Expressed in Sertoli cells in male testis. http://togogenome.org/gene/10090:Klhdc8b ^@ http://purl.uniprot.org/uniprot/Q9D2D9 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Involved in pinching off the separated nuclei at the cleavage furrow and in cytokinesis. Required for mitotic integrity and maintenance of chromosomal stability. Protects cells against mitotic errors, centrosomal amplification, micronucleus formation and aneuploidy. Plays a key role of midbody function involving abscission of the daughter cells during cytokinesis and appropriate chromosomal and nuclear segregation into the daughter cells.|||Midbody http://togogenome.org/gene/10090:Mrps33 ^@ http://purl.uniprot.org/uniprot/Q58DZ5|||http://purl.uniprot.org/uniprot/Q9D2R8 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mS33 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Procr ^@ http://purl.uniprot.org/uniprot/Q64695 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds activated protein C. Enhances protein C activation by the thrombin-thrombomodulin complex; plays a role in the protein C pathway controlling blood coagulation.|||Expressed in endothelial cells.|||Membrane http://togogenome.org/gene/10090:Eif2ak3 ^@ http://purl.uniprot.org/uniprot/E9QQ30|||http://purl.uniprot.org/uniprot/Q7TQC8|||http://purl.uniprot.org/uniprot/Q9Z2B5 ^@ Activity Regulation|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity.|||Autophosphorylated. Phosphorylated at Tyr-615 following endoplasmic reticulum stress, leading to activate its tyrosine-protein kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate its enzyme activity (By similarity). Oligomerization of the N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr-980 on the kinase activation loop.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily.|||By ER stress.|||Endoplasmic reticulum membrane|||Forms dimers with HSPA5/BIP in resting cells (PubMed:21543844). Oligomerizes in ER-stressed cells (PubMed:10854322). Interacts with DNAJC3 (PubMed:12446838). Interacts with MFN2 (PubMed:23921556). Interacts with TMEM33 (By similarity). Interacts with PDIA6 (By similarity). Interacts with LACC1 (By similarity).|||Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:9930704, PubMed:11106749, PubMed:23921556). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as unfolded protein response (UPR) and low amino acid availability (PubMed:9930704, PubMed:11106749, PubMed:23921556). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:11106749, PubMed:23921556). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (PubMed:11035797). Involved in control of mitochondrial morphology and function (PubMed:23921556).|||N-glycosylated.|||Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction.|||The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.|||Ubiquitous. http://togogenome.org/gene/10090:Cntnap2 ^@ http://purl.uniprot.org/uniprot/E9QNF7|||http://purl.uniprot.org/uniprot/Q9CPW0 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neurexin family.|||Detected at postnatal day 8 in sciatic nerve at the paranodes and the juxtaparanodal region. Is progressively translocated to the adjacent juxtaparanodal region until it becomes completely absent from the paranodes in the adult.|||In sciatic nerve predominantly found at the juxtaparanodal regions (at protein level).|||Interacts (via C-terminus) with KCNA2.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mutants don't show difference of Ranvier nodes length and width compared to wild-type littermates. Double mutants CNTNAP1 and CNTNAP2 have wider Ranvier nodes.|||Required for gap junction formation (By similarity). Required, with CNTNAP1, for radial and longitudinal organization of myelinated axons (PubMed:25378149). Plays a role in the formation of functional distinct domains critical for saltatory conduction of nerve impulses in myelinated nerve fibers. Demarcates the juxtaparanodal region of the axo-glial junction (Probable) (PubMed:25378149).|||axon|||paranodal septate junction http://togogenome.org/gene/10090:Vmn2r67 ^@ http://purl.uniprot.org/uniprot/K7N6T2 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm20881 ^@ http://purl.uniprot.org/uniprot/Q9D9T3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Qrfp ^@ http://purl.uniprot.org/uniprot/Q8CE23 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RFamide neuropeptide family.|||Expressed in the brain with highest levels in the periventricular hypothalamic nucleus and lateral hypothalamic areas. Expressed at moderate levels in the adrenal gland, eye, heart, intestine, liver, lung, kidney, mesenteric lymph node, ovary, placenta, Peyer patches, skin, spleen, stomach, testis, thymus and uterus.|||Ligand for the G-protein coupled receptor QRFPR/GPR103.|||Secreted|||Stimulates feeding and grooming behavior, metabolic rate and locomotor activity and increases blood pressure. May have orexigenic activity. May promote aldosterone secretion by the adrenal gland. http://togogenome.org/gene/10090:Figla ^@ http://purl.uniprot.org/uniprot/O55208 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected as early as embryonic day 13, shortly after the onset of sexual dimorphism of the gonads. Dramatically increases at the end of the embryonic development and peaks at 2 dpp, a time in ovarian development at which oocytes have become enclosed in primordial follicles. Decreases markedly by 7 and 14 days after birth. Persists, but at low level, in adult females. Not detected in male embryos, but detected in adult testes.|||Expressed only in the oocytes within the ovary and at lower level in the testis. Found in the resting oocytes of the primordial follicle cells, at the periphery of the ovary and in the hilar region. Also detected in growing oocytes, but at lower levels.|||Females display a defect in the formation of primordial follicles leading to infertility. Although embryonic gonadogenesis appeared normal, primordial follicles were not formed at birth, and massive depletion of oocytes resulted in shrunken ovaries and female sterility. Null females do not express ZP1, ZP2 or ZP3. Since its expression is oocyte-specific in females, Figla is a plausible candidate gene for primary ovarian failure in otherwise phenotypically normal women. The gene for Figla null males have normal fertility.|||Germ-line specific transcription factor implicated in postnatal oocyte-specific gene expression. Plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida (ZP1, ZP2 and ZP3) required for fertilization and early embryonic survival. Essential for oocytes to survive and form primordial follicles. The persistence of FIGLA in adult females suggests that it may regulate additional pathways that are essential for normal ovarian development. Binds to the E-box (5'-CANNTG-3') of the ZPs (ZP1, ZP2, ZP3) promoters.|||Heterodimer with TCF3/isoform E12.|||Nucleus http://togogenome.org/gene/10090:Csf1r ^@ http://purl.uniprot.org/uniprot/P09581|||http://purl.uniprot.org/uniprot/Q0P635|||http://purl.uniprot.org/uniprot/Q3UKC6|||http://purl.uniprot.org/uniprot/Q6NXV8 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated in response to CSF1 or IL34 binding. Phosphorylation at Tyr-559 is important for normal down-regulation of signaling by ubiquitination, internalization and degradation. Phosphorylation at Tyr-559 and Tyr-807 is important for interaction with SRC family members, including FYN, YES1 and SRC, and for subsequent activation of these protein kinases. Phosphorylation at Tyr-697 and Tyr-921 is important for interaction with GRB2. Phosphorylation at Tyr-721 is important for interaction with PIK3R1. Phosphorylation at Tyr-721 and Tyr-807 is important for interaction with PLCG2. Phosphorylation at Tyr-974 is important for interaction with CBL. Dephosphorylation by PTPN2 negatively regulates downstream signaling and macrophage differentiation.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell membrane|||Membrane|||Mice are born at slightly less than the expected Mendelian rate, and the number of surviving mice is significantly reduced after three weeks. Mice are considerably smaller than wild-type littermates and suffer from general skeletal deformities with shortened limbs, increased bone density, and decreased volume of femoral bone marrow. Mice have decreased numbers of circulating monocytes and lymphocytes, decreased numbers of tissue macrophages, paired with an increase in the number of circulating granulocytes. In addition, mice are deaf and have reduced male and female fertility. In females, the duration of the diestrous period is increased, and in pregnant females the lactating mammary gland fails to develop normally. Males mate less frequently and give rise to fewer pregnant females.|||Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts with INPPL1/SHIP2 and THOC5. Interacts (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2.|||Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580.|||The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity).|||The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase (By similarity).|||Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of pro-inflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding, including the ERK1/2 and the JNK pathway (By similarity). Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. In the central nervous system, may play a role in the development of microglia macrophages (By similarity).|||Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation.|||Widely expressed. http://togogenome.org/gene/10090:H4c3 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Fbxl17 ^@ http://purl.uniprot.org/uniprot/Q9QZN1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FBXL17 family.|||Cytoplasm|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL17) composed of CUL1, SKP1, RBX1 and FBXL17. Interacts with BTB domain-containing proteins such as KLHL12, BCL6 and BACH1; specifically recognizes and binds a conserved degron of non-consecutive residues present at the interface of BTB dimers of aberrant composition. Interacts with SUFU (By similarity). Interacts with PRMT1 (PubMed:28883095).|||Substrate-recognition component of the SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC). FBXL17 specifically recognizes and binds a conserved degron of non-consecutive residues present at the interface of BTB dimers of aberrant composition: aberrant BTB dimer are then ubiquitinated by the SCF(FBXL17) complex and degraded by the proteasome (By similarity). The ability of the SCF(FBXL17) complex to eliminate compromised BTB dimers is required for the differentiation and survival of neural crest and neuronal cells (By similarity). The SCF(FBXL17) complex mediates ubiquitination and degradation of BACH1 (By similarity). The SCF(FBXL17) complex is also involved in the regulation of the hedgehog/smoothened (Hh) signaling pathway by mediating the ubiquitination and degradation of SUFU, allowing the release of GLI1 from SUFU for proper Hh signal transduction (PubMed:27234298). The SCF(FBXL17) complex mediates ubiquitination and degradation of PRMT1 (PubMed:28883095). http://togogenome.org/gene/10090:Septin3 ^@ http://purl.uniprot.org/uniprot/Q9Z1S5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cytoplasm|||Expressed in the brain including the cerebrum, hippocampus and cerebellum (at protein level).|||Expressed in the cerebral cortex from 13.5 dpc to P30, expression peaks at P15.|||Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential).|||Phosphorylated by PKG on serine residues. Phosphorylated by PKG on Ser-91 (By similarity).|||Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation (By similarity).|||Synapse|||cytoskeleton http://togogenome.org/gene/10090:Mrpl55 ^@ http://purl.uniprot.org/uniprot/Q9CZ83 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL55 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ankrd34b ^@ http://purl.uniprot.org/uniprot/Q3UUF8 ^@ Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ANKRD34 family.|||Cytoplasm|||Nucleus|||Phosphorylated.|||Specifically and constitutively expressed in brain (at protein level).|||Up-regulated in bone marrow upon differentiation (at protein level). http://togogenome.org/gene/10090:Arl6 ^@ http://purl.uniprot.org/uniprot/O88848|||http://purl.uniprot.org/uniprot/Q3TUM2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Arf family.|||Interacts with SEC61B, ARL6IP1, ARL6IP2, ARL6IP3, ARL6IP4 ARL6IP5 and ARL6IP6. Interacts (GTP-bound form) with the BBSome a complex that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts (GTP-free form) with IFT27.|||Involved in membrane protein trafficking at the base of the ciliary organelle (By similarity). Mediates recruitment onto plasma membrane of the BBSome complex which would constitute a coat complex required for sorting of specific membrane proteins to the primary cilia (By similarity). Together with BBS1, is necessary for correct trafficking of PKD1 to primary cilia (PubMed:24939912). Together with the BBSome complex and LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation (By similarity). May regulate cilia assembly and disassembly and subsequent ciliary signaling events such as the Wnt signaling cascade (By similarity). Isoform 2 may be required for proper retinal function and organization (PubMed:20333246).|||Isoform 2 deficient mice present a disruption of the normal photoreceptor architecture.|||Most abundant in brain and kidney. Expressed in heart and eye. Isoform 2 is expressed only in the retina.|||cilium axoneme|||cilium basal body|||cilium membrane http://togogenome.org/gene/10090:Golga5 ^@ http://purl.uniprot.org/uniprot/Q9QYE6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Golgi apparatus membrane|||Highly phosphorylated during mitosis. Phosphorylation is barely detectable during interphase (By similarity).|||Homodimer. Interacts with RAB1A that has been activated by GTP-binding. Interacts with isoform CASP of CUX1 (By similarity).|||Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport (By similarity). http://togogenome.org/gene/10090:Armc8 ^@ http://purl.uniprot.org/uniprot/G3X920|||http://purl.uniprot.org/uniprot/Q9DBR3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1.|||Cytoplasm|||Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles.|||Nucleus http://togogenome.org/gene/10090:Syn1 ^@ http://purl.uniprot.org/uniprot/O88935 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synapsin family.|||Golgi apparatus|||Homodimer (By similarity). Can form oligomers with SYN2 (By similarity). Interacts with CAPON (By similarity). Forms a ternary complex with NOS1 (By similarity). Isoform Ib interacts with PRNP (PubMed:11571277).|||Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton. Acts as a regulator of synaptic vesicles trafficking, involved in the control of neurotransmitter release at the pre-synaptic terminal (By similarity). Also involved in the regulation of axon outgrowth and synaptogenesis (PubMed:7568107). The complex formed with NOS1 and CAPON proteins is necessary for specific nitric-oxide functions at a presynaptic level (By similarity).|||Presynapse|||Substrate of different protein kinases. Phosphorylation, including phosphorylation at Ser-9, promotes synapsin-1 dissociation from synaptic vesicles, regulates its rate of dispersion, and controls the kinetics of vesicle pool turnover.|||Synapse|||The A region binds phospholipids with a preference for negatively charged species.|||synaptic vesicle http://togogenome.org/gene/10090:Slc17a3 ^@ http://purl.uniprot.org/uniprot/G3UWD9|||http://purl.uniprot.org/uniprot/Q5SZ92 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:a ^@ http://purl.uniprot.org/uniprot/A0A510NUK5|||http://purl.uniprot.org/uniprot/Q03288 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Epithelial cells of the hair follicles and the epidermis.|||Involved in the regulation of melanogenesis. The binding of ASP to MC1R precludes alpha-MSH initiated signaling and thus blocks production of cAMP, leading to a down-regulation of eumelanogenesis (brown/black pigment) and thus increasing synthesis of pheomelanin (yellow/red pigment). Causes hair follicle melanocytes to synthesize phaeomelanin instead of black or brown pigment eumelanin and produces hairs with a subapical yellow band on an otherwise black or brown background when expressed during the mid-portion of hair growth.|||Secreted|||The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.|||The products of the Gag polyproteins of infectious retroviruses perform highly complex orchestrated tasks during the assembly, budding, maturation, and infection stages of the viral replication cycle. During viral assembly, the proteins form membrane associations and self-associations that ultimately result in budding of an immature virion from the infected cell. Gag precursors also function during viral assembly to selectively bind and package two plus strands of genomic RNA. Endogenous Gag proteins may have kept, lost or modified their original function during evolution.|||Widely expressed in embryonic and neonatal skin. http://togogenome.org/gene/10090:Gpt ^@ http://purl.uniprot.org/uniprot/Q566C3|||http://purl.uniprot.org/uniprot/Q8QZR5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family. Alanine aminotransferase subfamily.|||Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with precursors transported from skeletal muscles (By similarity).|||Cytoplasm|||Homodimer.|||Mainly expressed in liver, intestine, colon and white adipose tissue. http://togogenome.org/gene/10090:Cox8a ^@ http://purl.uniprot.org/uniprot/Q64445 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIII family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Cpne5 ^@ http://purl.uniprot.org/uniprot/Q8JZW4 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the copine family.|||Binds 3 Ca(2+) ions per C2 domain.|||Cell projection|||Expressed at the ventricular zone and subventricular zone areas, in the tectum, frontal cortex, ganglionic eminence, dorsal thalamus, hippocampus and tegmentum of the embryonic brain from 12.5 to 14.5 dpc. Expressed in neural progenitor cells (at protein level). Expressed in the embryonic brain from 10.5 to 17.5 dpc. Expressed in the telencephalon, mesencephalon and rhombencephalon areas from 11.5 to 12.5 dpc. Expressed in the developing central nervous system (CNS), such as the frontal cortex, hypothalamus and ventricular zones along the IV ventricle and aquaeductus mesencephali at 13.5 dpc (PubMed:18614158).|||Expressed in the cerebra and cerebellum of newborn brain. Expressed in the eye, lung and muscles but weakly expressed in the adult brain (at protein level) (PubMed:18614158).|||Perikaryon|||Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes. Plays a role in dendrite formation by melanocytes. http://togogenome.org/gene/10090:Tmem62 ^@ http://purl.uniprot.org/uniprot/Q8BXJ9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Sfta2 ^@ http://purl.uniprot.org/uniprot/E9PXB6 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Down-regulated in response to LPS (lipopolysaccharide) challenge.|||Expressed in lung, and specifically in alveolar type II epithelial cells.|||Golgi apparatus|||N-glycosylated.|||Putative surfactant protein.|||Secreted|||secretory vesicle http://togogenome.org/gene/10090:Kcnk12 ^@ http://purl.uniprot.org/uniprot/Q76M80 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Membrane http://togogenome.org/gene/10090:Tas2r110 ^@ http://purl.uniprot.org/uniprot/Q7M712 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5 (By similarity).|||Membrane|||Several bitter taste receptors with distinct ligand specificities are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Dot1l ^@ http://purl.uniprot.org/uniprot/Q6XZL8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.|||Histone methyltransferase that specifically trimethylates histone H3 to form H3K79me3. This methylation is required for telomere silencing and for the pachytene checkpoint during the meiotic cell cycle by allowing the recruitment of RAD9 to double strand breaks. Nucleosomes are preferred as substrate compared to free histone.|||Histone methyltransferase. Methylates 'Lys-79' of histone H3.|||In contrast to other lysine histone methyltransferases, it does not contain a SET domain, suggesting the existence of another mechanism for methylation of lysine residues of histones.|||Nucleus http://togogenome.org/gene/10090:Frmd6 ^@ http://purl.uniprot.org/uniprot/Q8C0V9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Cytoplasm http://togogenome.org/gene/10090:Myh7b ^@ http://purl.uniprot.org/uniprot/A2AQP0 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Involved in muscle contraction.|||Membrane|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||Represents a conventional myosin. This protein should not be confused with the unconventional myosin-7 (MYO7).|||The cardiac alpha isoform is a 'fast' ATPase myosin, while the beta isoform is a 'slow' ATPase. http://togogenome.org/gene/10090:Arap2 ^@ http://purl.uniprot.org/uniprot/E9QP44 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Pvalb ^@ http://purl.uniprot.org/uniprot/P32848|||http://purl.uniprot.org/uniprot/Q545M7 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the parvalbumin family.|||Expressed in the modiolar nerve root (at protein level).|||In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions. http://togogenome.org/gene/10090:Yars ^@ http://purl.uniprot.org/uniprot/A2A7S7|||http://purl.uniprot.org/uniprot/Q91WQ3 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Cytoplasm|||Homodimer. Interacts (when binding to resveratrol) with PARP1; interaction stimulates the poly-ADP-ribosyltransferase activity of PARP1.|||Nucleus|||Resveratrol strongly inhibits the tyrosine--tRNA ligase activity.|||The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound.|||Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (By similarity). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (By similarity). Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949). http://togogenome.org/gene/10090:Terb1 ^@ http://purl.uniprot.org/uniprot/Q8C0V1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TERB1 family.|||Component of the MAJIN-TERB1-TERB2 complex, composed of MAJIN, TERB1 and TERB2 (PubMed:26548954). Interacts with TERF1, STAG3 and SUN1 (PubMed:24413433). Interacts (via Myb-like domain) with the cohesin complex; probably mediated via interaction with STAG3 (PubMed:24413433).|||Expressed during meiotic prophase and becomes undetectable in metaphase I in spermatocytes and oocytes (at protein level).|||Expressed in testis and fetal oocytes.|||Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis (PubMed:24885367, PubMed:24413433, PubMed:26548954). Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA (PubMed:26548954). In the MAJIN-TERB1-TERB2 complex, TERB1 probably mediates association with the shelterin/telosome complex via interaction with TERF1, promoting priming telomeric DNA attachment' (PubMed:26548954). Promotes telomere association with the nuclear envelope and deposition of the SUN-KASH/LINC complex (PubMed:24885367, PubMed:24413433). Also recruits cohesin to telomeres to develop structural rigidity (PubMed:24413433).|||Mice develop normally, exhibit no overt phenotype, but are infertile (both males and females). Testis lack postmeiotic cells due to massive elimination of spermatocytes, while females show degeneration of the ovaries, lacking growing follicles and mature oocytes.|||Nucleus inner membrane|||Phosphorylated by CDK (PubMed:24413433, PubMed:26548954). Phosphorylation by CDK takes place in late prophase when the cap exchange is prominent (PubMed:26548954). is important for the stabilization of telomere attachment but dispenable for the cap exchange (PubMed:26548954).|||telomere http://togogenome.org/gene/10090:Pttg1ip ^@ http://purl.uniprot.org/uniprot/Q8R143 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Interacts with PTTG1.|||May facilitate PTTG1 nuclear translocation.|||Nucleus http://togogenome.org/gene/10090:Cdc73 ^@ http://purl.uniprot.org/uniprot/Q8JZM7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CDC73 family.|||Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. The PAF1 complex interacts with PHF5A (PubMed:27749823). Within the PAF1 complex interacts directly with PHF5A (PubMed:27749823). Interacts with POLR2A, CPSF1, CPSF4, CSTF2, KMT2A/MLL1 and CTNNB1. Interacts with a Set1-like complex that has histone methyltransferase activity and methylates histone H3. Found in a complex with BCL9L or BCL9, CDC73, CTNNB1 and PYGO1 indicative for the participation in a nuclear Wnt signaling complex. Interacts with PTPN11 (By similarity). Interacts with SETD5 (PubMed:27864380).|||Found in the adrenal gland, kidney, heart, ovary and liver.|||Nucleus|||Phosphorylated. Dephosphorylated by PTPN11.|||Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. Connects PAF1C with the cleavage and polyadenylation specificity factor (CPSF) complex and the cleavage stimulation factor (CSTF) complex, and with Wnt signaling. Involved in polyadenylation of mRNA precursors (By similarity). http://togogenome.org/gene/10090:Prkca ^@ http://purl.uniprot.org/uniprot/P20444|||http://purl.uniprot.org/uniprot/Q4VA93 ^@ Activity Regulation|||Cofactor|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.|||Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP. Depending on the cell type, is involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation. In cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (By similarity). Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (PubMed:31578312). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity).|||Cell membrane|||Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation.|||Cytoplasm|||Expression of the mutant form UV25 causes malignant transformation of cells.|||Interacts with ADAP1/CENTA1 and CSPG4 (By similarity). Interacts with PRKCABP (PubMed:7844141). Binds to CAVIN2 in the presence of phosphatidylserine. Interacts with PICK1 (via PDZ domain). Interacts with TRIM41 (By similarity). Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and RACK1 (PubMed:20093473). Interacts with PARD3 (By similarity). Interacts with SOCS2 (PubMed:31578312).|||Membrane|||Mitochondrion membrane|||Nucleus http://togogenome.org/gene/10090:Ankrd52 ^@ http://purl.uniprot.org/uniprot/Q8BTI7 ^@ Function|||Subunit ^@ Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS). Interacts with PPP6R1 (By similarity).|||Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates. http://togogenome.org/gene/10090:Ptcd1 ^@ http://purl.uniprot.org/uniprot/Q8C2E4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with mitochondrial leucine tRNAs. Interacts with ELAC2.|||Belongs to the PTCD1 family.|||Mitochondrial protein implicated in negative regulation of leucine tRNA levels, as well as negative regulation of mitochondria-encoded proteins and COX activity. Affects also the 3'-processing of mitochondrial tRNAs.|||Mitochondrion|||Mitochondrion matrix http://togogenome.org/gene/10090:Helz ^@ http://purl.uniprot.org/uniprot/Q6DFV5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA2/NAM7 helicase family.|||Interacts with POLR2A. Interacts with SMYD3; the interaction may bridge SMYD3 and RNA polymerase II (By similarity). Interacts with SMYD2.|||May act as a helicase that plays a role in RNA metabolism in multiple tissues and organs within the developing embryo.|||May be due to intron retention.|||Nucleus http://togogenome.org/gene/10090:Smox ^@ http://purl.uniprot.org/uniprot/Q99K82 ^@ Cofactor|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Active. Nuclear and cytoplasmic.|||Belongs to the flavin monoamine oxidase family.|||Binds 1 FAD per subunit.|||By antitumor polyamine analogs.|||Cytoplasm|||Flavoenzyme which catalyzes the oxidation of spermine to spermidine. Can also use N(1)-acetylspermine and spermidine as substrates, with different affinity depending on the isoform (isozyme) and on the experimental conditions. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs. May contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-amino-propanal.|||Major isoform.|||No detectable activity. Cytoplasmic.|||Nucleus|||Widely expressed. Isoform 1 and isoform 2 are expressed at higher level in brain and skeletal muscle. Isoform 7 is found in brain and spleen, isoform 10 is widely expressed but found at lower level in heart, kidney, liver and lung. http://togogenome.org/gene/10090:Trpm1 ^@ http://purl.uniprot.org/uniprot/Q2TV84 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM1 sub-subfamily.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed in the retina where it localizes on dendritic tips of ON bipolar cells. Specifically, it is expressed in retinal bipolar cells (BPCs) of the ON subtype (PubMed:30027108). Not detected in brain, lung, liver, heart, kidney, spleen or small intestine. Also expressed at high levels in poorly metastatic variants of B16 melanoma and at much reduced levels in highly metastatic variants of B16 melanoma.|||Forms nonselective divalent cation-conducting channels which mediate the influx of Na(2+), Ca(2+), Mg(2+), Mn(2+), Ba(2+), and Ni(2+) into the cytoplasm, leading to membrane depolarization (By similarity). Impermeable to zinc ions (By similarity). In addition, forms heteromultimeric ion channels with TRPM3 which are permeable for calcium and zinc ions (By similarity). Essential for the depolarizing photoresponse of retinal ON bipolar cells. It is part of the GRM6 signaling cascade. Calcium channel which may play a role in metastasis suppression. May act as a spontaneously active, calcium-permeable plasma membrane channel.|||Inhibited by zinc ions.|||Interacts with TRPM3; the interaction results in the formation of a heteromultimeric cation channel complex (By similarity). Interacts with GPR179 (PubMed:24114537, PubMed:24790204).|||axon http://togogenome.org/gene/10090:Thap7 ^@ http://purl.uniprot.org/uniprot/Q8VCZ3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Chromatin-associated, histone tail-binding protein that represses transcription via recruitment of HDAC3 and nuclear hormone receptor corepressors.|||Chromosome|||Interacts with HDAC3 and nuclear hormone receptor corepressors.|||Nucleus http://togogenome.org/gene/10090:Wdr1 ^@ http://purl.uniprot.org/uniprot/O88342 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat AIP1 family.|||Embryonic lethal. Partial deficiencies disrupt megakaryocyte maturation, platelet shedding and provoke neutrophilic autoinflammatory disease.|||Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (By similarity). Enhances cofilin-mediated actin severing (PubMed:25915128). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (By similarity). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth at the postnatal and maintenance at the adult stage (PubMed:24840128). Involved in neutrophil actin dynamics and migration. Involved in megakaryocyte maturation and platelet shedding (PubMed:17515402). Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (PubMed:25915128). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (By similarity).|||cytoskeleton|||podosome http://togogenome.org/gene/10090:Fbxl16 ^@ http://purl.uniprot.org/uniprot/A2RT62 ^@ Function|||Subunit ^@ Interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:4931406C07Rik ^@ http://purl.uniprot.org/uniprot/Q91V76 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.|||Monomer.|||Nucleus http://togogenome.org/gene/10090:4933402N03Rik ^@ http://purl.uniprot.org/uniprot/Q8CDT9 ^@ Disruption Phenotype|||Function|||Tissue Specificity ^@ Dispensable for normal development and fertility.|||Expressed in testis and epididymis (PubMed:36871790). Expressed at lower levels in ovary (PubMed:36871790).|||No visible phenotype (PubMed:36871790). No effect on testis size, testis-to-body weight ratio, germ cell development or spermiogenesis (PubMed:36871790). No effect on sperm morphology, count or motility (PubMed:36871790). No effect on levels of germ cell apoptosis, chromosome H1t histone association or acrosome biogenesis (PubMed:36871790). http://togogenome.org/gene/10090:Srd5a3 ^@ http://purl.uniprot.org/uniprot/Q9WUP4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the steroid 5-alpha reductase family. Polyprenol reductase subfamily.|||Death by 12.5 dpc. At 10.5 dpc, embryos are smaller and fail to undergo axial rotation observed at 8.5 dpc in wild-types and present dilated hearts and open neural tubes.|||Endoplasmic reticulum membrane|||Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol (PubMed:20637498). Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation (PubMed:20637498). Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism (PubMed:20637498). Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT) (By similarity). http://togogenome.org/gene/10090:Ubtfl1 ^@ http://purl.uniprot.org/uniprot/Q3USZ2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Cytoplasm|||Essential for proliferation of the inner cell mass and trophectodermal cells in peri-implantation development.|||Nucleus|||Transcriptionally activated at the 2-cell stage, peaks at the 4-cell stage and then gradually decreased until the blastocyst stage. The protein is detected from the 4-cell stage until the blastocyst stage. In blastocysts, expressed both by inner cell mass and trophectodermal cells (at protein level). Not detected in post-implentation, neither in fetal, nor adult tissues. http://togogenome.org/gene/10090:Micos13 ^@ http://purl.uniprot.org/uniprot/Q8R404 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MICOS complex subunit Mic13 family.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Constituent of mature MICOS complex, it is required for the formation of cristae junction (CJ) and maintenance of cristae morphology. Required for the incorporation of MICOS10/MIC10 into the MICOS complex.|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOO/MIC26, MICOS13/MIC13, APOOL/MIC27 and IMMT/MIC60. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Edf1 ^@ http://purl.uniprot.org/uniprot/Q9JMG1 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain, liver, kidney and heart (at protein level). Also expressed in testis.|||Interacts with TBP and the transcription factor IID (TFIID) complex, NR5A2, NR1H3 and PPARG. Interaction with TBP is regulated by phosphorylation. Binds NR5A1, ATF1, FOS and JUN via their conserved basic region. Binding to calmodulin is regulated by calcium and phosphorylation of the IQ motif (By similarity).|||Nucleus|||Phosphorylated.|||The IQ motif, which is involved in calmodulin binding, overlaps with the binding domain for nuclear receptors and transcription factors. Its phosphorylation probably allows a switch between the two activities of the protein (By similarity).|||Transcriptional coactivator stimulating NR5A1 and ligand-dependent NR1H3/LXRA and PPARG transcriptional activities. Enhances the DNA-binding activity of ATF1, ATF2, CREB1 and NR5A1. Regulates nitric oxid synthase activity probably by sequestering calmodulin in the cytoplasm. Might function in endothelial cells differentiation, hormone-induced cardiomyocytes hypertrophy and lipid metabolism (By similarity).|||Very highly expressed seven days after implantation, when gastrulation and neurulation occurs. Expression decreases 11 days after implantation, when organogenesis is being completed, and remains rather low up to late developmental stages. http://togogenome.org/gene/10090:Tha1 ^@ http://purl.uniprot.org/uniprot/Q6XPS7 ^@ Similarity ^@ Belongs to the threonine aldolase family. http://togogenome.org/gene/10090:Tmem131 ^@ http://purl.uniprot.org/uniprot/O70472 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM131 family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||May play a role in the immune response to viral infection.|||Membrane http://togogenome.org/gene/10090:Nmt1 ^@ http://purl.uniprot.org/uniprot/O70310|||http://purl.uniprot.org/uniprot/Q3UJC3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins (PubMed:15753093). Also able to mediate N-terminal lysine myristoylation of proteins: catalyzes myristoylation of ARF6 on both 'Gly-2' and 'Lys-3' (By similarity). Lysine myristoylation is required to maintain ARF6 on membranes during the GTPase cycle (By similarity). Required for normal embryogenesis (PubMed:15753093).|||Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.|||Belongs to the NMT family.|||Complete embryonic lethality. Embryos die between 3.5 and 7.5 dpc.|||Cytoplasm|||Membrane|||Ubiquitous.|||cytosol http://togogenome.org/gene/10090:H3c4 ^@ http://purl.uniprot.org/uniprot/B9EI85|||http://purl.uniprot.org/uniprot/P84228 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. During nucleosome assembly the chaperone ASF1A interacts with the histone H3-H4 heterodimer (By similarity). Interacts with DNAJC9, CHAF1A and CHAF1B (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Lgi4 ^@ http://purl.uniprot.org/uniprot/Q8K1S1 ^@ Developmental Stage|||Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Brain. Expressed in the entire developing peripheral nerves. Strongly expressed in the trigeminal nerve and ganglion and particularly abundant in the boundary cap cells - a transient population of cells that contributes to the Schwann cell population of the dorsal root nerve.|||Can bind to ADAM11, ADAM22 and ADAM23.|||Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation.|||Defects in Lgi4 are the cause of the claw paw (clp) phenotype. Mice are characterized by limb posture abnormalities and peripheral hypomyelination, with no sign of dysmyelination in the CNS.|||Expressed at 14 dpc.|||Secreted http://togogenome.org/gene/10090:Snx25 ^@ http://purl.uniprot.org/uniprot/Q3ZT31 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||Endosome membrane|||Intron retention.|||May be involved in several stages of intracellular trafficking. http://togogenome.org/gene/10090:Muc4 ^@ http://purl.uniprot.org/uniprot/Q8JZM8 ^@ Domain|||Function|||PTM|||Polymorphism|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A heterodimeric complex, composed of a mucin-4 alpha chain and a cysteine-rich transmembrane mucin-4 beta chain. Mucin-4 beta chain interacts with ERBB2 via the EGF-like domain 1. In nonpolarized cells, associates with ERBB2 and ERBB3.|||Cell membrane|||Essentially composed of an array of serine- and threonine-rich tandem repeats which is highly polymorphic, the variable number of tandem repeats (VNTR) region.|||Expressed in trachea, duodenum and intestine. Lower expression in stomach, salivary glands, liver, gallbladder, and kidney.|||Highly O-glycosylated.|||Membrane-bound mucin, a family of highly glycosylated proteins that constitute the major component of the mucus, the slimy and viscous secretion covering epithelial surfaces. These glycoproteins play important roles in the protection of the epithelium and are implicated in epithelial renewal and differentiation. Regulates cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and its ability to act as an intramembrane ligand for ERBB2. Plays an important role in proliferation and differentiation of epithelial cells by inducing specific phosphorylation of ERBB2. In polarized epithelial cells, segregates ERBB2 and other ERBB receptors and prevents ERBB2 from acting as a coreceptor. The interaction with ERBB2 leads to enhanced expression of CDKN1B. The formation of a MUC4-ERBB2-ERBB3-NRG1 complex leads to down-regulation of CDKN1B, resulting in repression of apoptosis and stimulation of proliferation. Its ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation.|||Predominantly N-glycosylated.|||Proteolytically cleaved into 2 chains, mucin-4 alpha chain and mucin-4 beta chain.|||Secreted|||The sequence differs significantly from the reference genome sequence for various reasons.|||The variable number of tandem repeats (VNTR) region, an array of serine- and threonine-rich tandem repeats, is encoded by a single exon (exon 2) which is highly polymorphic. http://togogenome.org/gene/10090:Il33 ^@ http://purl.uniprot.org/uniprot/Q8BVZ5 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Interacts (in reduced form) with H.polygyrus ARI; the interaction abolishes the interaction with its primary receptor IL1RL1.|||Belongs to the IL-1 family. Highly divergent.|||By cold stress, and by infection with the fungus A.alternata and the parasite H.polygyrus.|||Chromosome|||Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:29045903). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines (By similarity). Also involved in activation of mast cells, basophils, eosinophils and natural killer cells (By similarity). Acts as an enhancer of polarization of alternatively activated macrophages (By similarity). Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury (By similarity). Induces rapid UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (PubMed:34644537).|||Cytoplasm|||Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets (By similarity). This form is rapidely lost upon angiogenic or pro-inflammatory activation (By similarity).|||Intraperitoneal injections of IL-33 induce the expression of IL-4, IL-5, and IL-13 and lead to severe pathological changes in mucosal organs.|||Nucleus|||Secreted|||The full-length protein can be released from cells and is able to signal via the IL1RL1/ST2 receptor (PubMed:16286016). However, proteolytic processing by CELA1, CSTG/cathepsin G and ELANE/neutrophil elastase produces C-terminal peptides that are more active than the unprocessed full-length protein (PubMed:22307629, PubMed:35749514). May also be proteolytically processed by calpains. Proteolytic cleavage mediated by apoptotic caspases including CASP3 and CASP7 results in IL33 inactivation (PubMed:16286016, PubMed:19465481). In vitro proteolytic cleavage by CASP1 was reported (PubMed:16286016) but could not be confirmed in vivo (PubMed:19465481) suggesting that IL33 is probably not a direct substrate for that caspase (PubMed:16286016, PubMed:19465481).|||The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.|||secretory vesicle http://togogenome.org/gene/10090:Fads1 ^@ http://purl.uniprot.org/uniprot/Q920L1 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 5 located between a preexisting double bond and the carboxyl end of the fatty acyl chain. Involved in biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors. Specifically, desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to generate arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3), respectively (Probable). As a rate limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived eicosanoid biosynthesis, controls the metabolism of inflammatory lipids like prostaglandin E2, critical for efficient acute inflammatory response and maintenance of epithelium homeostasis. Contributes to membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major acyl chain esterified into phospholipids. In particular, regulates phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory cytokine production in T-cells (PubMed:22534642). Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of LA (18:2n-6) (By similarity).|||Belongs to the fatty acid desaturase type 1 family.|||Endoplasmic reticulum membrane|||Expression in liver is down-regulated by dietary PUFA.|||Highly expressed in the adrenal gland, liver, brain, and testis, tissues where lipogenesis and steroidogenesis are active (PubMed:11792729). Expressed in colonic mucosa (PubMed:22534642).|||Knockout mice die prematurely with no survivors past 12 weeks of age. This phenotype can be rescued by adding arachidonic acid (AA) to the diet.|||Mitochondrion|||The histidine box domains may contain the active site and/or be involved in metal ion binding. http://togogenome.org/gene/10090:Sgf29 ^@ http://purl.uniprot.org/uniprot/Q9DA08 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SGF29 family.|||Chromatin reader component of some histone acetyltransferase (HAT) SAGA-type complexes like the TFTC-HAT, ATAC or STAGA complexes (By similarity). SGF29 specifically recognizes and binds methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3) (By similarity). In the SAGA-type complexes, SGF29 is required to recruit complexes to H3K4me (By similarity). Involved in the response to endoplasmic reticulum (ER) stress by recruiting the SAGA complex to H3K4me, thereby promoting histone H3 acetylation and cell survival (By similarity). Also binds non-histone proteins that are methylated on Lys residues: specifically recognizes and binds CGAS monomethylated on 'Lys-491' (PubMed:35210392).|||Interacts with dimethylated and trimethylated 'Lys-4' of histone H3 (H3K4me2 and H3K4me3), with a preference for the trimethylated form (H3K4me3) (By similarity). Component of some SAGA-type complexes. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). Interacts with (methylated) CGAS (PubMed:35210392). Interacts with TADA3L, GCN5L2, SUPT3H and MYC (By similarity).|||Nucleus|||The SGF29 C-terminal (also named tudor-like) domain mediates binding to methylated 'Lys-4' of histone H3 (H3K4me). http://togogenome.org/gene/10090:Or2y11 ^@ http://purl.uniprot.org/uniprot/Q7TQT4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or2y15 ^@ http://purl.uniprot.org/uniprot/Q8VFA9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tbx18 ^@ http://purl.uniprot.org/uniprot/G3X919|||http://purl.uniprot.org/uniprot/Q8C003|||http://purl.uniprot.org/uniprot/Q9EPZ6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Acts as transcriptional repressor involved in developmental processes of a variety of tissues and organs, including the heart, the coronary vessels, the ureter, and the vertebral column. Required for embryonic development of the sino atrial node (SAN) head area.|||Deficient mice fail to maintain anterior-posterior polarity, resulting in abnormal dorsal-ventral polarity of the somites. Mutant mice display neonatal lethality and abnormal morphology of vertebrae, ribs, spinal nerves and coronary vessels. Besides, mutant mice develop anomalies of the urinary tract, including hydroureter and hydronephrosis.|||Expressed in the renal pelvis and ureter smooth muscle layer at 17.5 dpc (at protein level) (PubMed:26235987). During development expression is most prominent in the proepicardial organ and in the epicardium. Expressed also in the cranial paraxial mesoderm, the presomitic mesoderm, the anterior somite half, the genital ridge and the developing limb buds (PubMed:11118889).|||Homodimer. Can form a heterodimer with TBX15. Interacts with GATA4 and NKX2-5. Interacts (via engrailed homology 1 repressor motif) with TLE3; this interaction represses TBX18 transcriptional activity. Interacts with PAX3. Interacts with SIX1 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus http://togogenome.org/gene/10090:Vopp1 ^@ http://purl.uniprot.org/uniprot/Q8R1C3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VOPP1/ECOP family.|||Cytoplasmic vesicle membrane|||Increases the transcriptional activity of NFKB1 by facilitating its nuclear translocation, DNA-binding and associated apoptotic response, when overexpressed. May sequester WWOX in lysosomal vesicles and thereby regulate WWOX role as tumor suppressor.|||Interacts with WWOX (via WW domain).|||Late endosome membrane|||Lysosome membrane http://togogenome.org/gene/10090:Ankrd24 ^@ http://purl.uniprot.org/uniprot/Q80VM7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Componement of the stereocilia rootlet in hair cells of inner ear. Bridges the apical plasma membrane with the lower rootlet and maintains normal distribution of TRIOBP, thereby reinforcing stereocilia insertion points and organizing rootlets for hearing with long-term resilience.|||Deficient mice exhibit progressive hearing loss. Loss of Ankrd24 induces morphological changes in hair bundles, early postnatal hair bundles are warped. Stereocilia of deficient mice show diminished recovery of auditory function after noise damage and increased susceptibility to overstimulation of the hair bund.|||Expressed in vestibular hair bundles.|||Homodimer (PubMed:35175278). Interacts (via C-terminal domain) with TRIOBP (via C-terminal domain) isoform 4; recruits TRIOBP isoform 4 to stereocilia rootlets (PubMed:35175278).|||Prominently associated with the stereocilia rootlet in outer hair cells (OHCs), inner hair cells (IHCs), and vestibular (utricle) hair cells (VHCs) on postnatal day 7.5. On postnatal day 1.5, is initially present in outer hair cells (OHCs) and inner hair cells (IHCs) as well as at the rootlets. At postnatal day 19.5 is concentrated at stereocilia insertion points.|||stereocilium http://togogenome.org/gene/10090:Vmn1r100 ^@ http://purl.uniprot.org/uniprot/Q9EPS5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r221 ^@ http://purl.uniprot.org/uniprot/A0A494B935 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kcnk2 ^@ http://purl.uniprot.org/uniprot/P97438|||http://purl.uniprot.org/uniprot/Q6P6P9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Cell membrane|||Detected in hippocampus astrocytes (at protein level) (PubMed:24496152). High expression in brain and lung. Also detected in kidney, heart and skeletal muscle. Not detected in liver. In the brain, highest expression in olfactory bulb, hippocampus and cerebellum.|||Homodimer; disulfide-linked (PubMed:24496152). Heterodimer with KCNK1; disulfide-linked (PubMed:24496152). Interacts with BVES; the interaction enhances KCNK2 surface expression and is inhibited by cAMP (PubMed:22354168, PubMed:26642364).|||Inhibited by barium (PubMed:9003761). Activated by volatile general anesthetics such as chloroform, diethyl ether, halothane and isoflurane (PubMed:10321245).|||Ion channel that contributes to passive transmembrane potassium transport. Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner. In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2 (PubMed:24496152). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (PubMed:24496152).|||Membrane|||Phosphorylation at Ser-348 controls the reversible conversion from a leak channel to a voltage-dependent channel. http://togogenome.org/gene/10090:Vtcn1 ^@ http://purl.uniprot.org/uniprot/Q7TSP5 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Cell membrane|||Down-regulated upon activation of B-cells.|||Expressed on the surface of professional antigen-presenting cells (at protein level). Widely expressed, including in kidney, liver, lung, pancreas, placenta, prostate, spleen, testis and thymus.|||Mice mount mildy augmented T-helper 1 responses and display slightly lowered parasitic burdens upon Leishmania major infection.|||N-glycosylated.|||Negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. Involved in promoting epithelial cell transformation. http://togogenome.org/gene/10090:Tle3 ^@ http://purl.uniprot.org/uniprot/E0CXS9|||http://purl.uniprot.org/uniprot/F8WIE2|||http://purl.uniprot.org/uniprot/Q08122|||http://purl.uniprot.org/uniprot/Q80TC1 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat Groucho/TLE family.|||Expressed only in testis (PubMed:8365415). Expressed in bone marrow-derived macrophages (PubMed:23990468).|||Homotetramer and heterooligomer with other family members. Binds FOXA2 (By similarity). Interacts with XIAP/BIRC4 (By similarity). Binds LEF1, TCF7, TCF7L1 and TCF7L2/TCF4. Interacts with TBX18 (via engrailed homology 1 repressor motif), leading to decreased of TBX18 transcriptional activity.|||Nucleus|||Repressed during TNFSF11/RANKL-induced osteoclast differentiation.|||Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity). May play an important role during spermatogenesis.|||Ubiquitinated by XIAP/BIRC4. This ubiquitination does not affect its stability, nuclear localization, or capacity to tetramerize but inhibits its interaction with TCF7L2/TCF4.|||WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain. http://togogenome.org/gene/10090:Or8g55 ^@ http://purl.uniprot.org/uniprot/Q9EQA2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prss23 ^@ http://purl.uniprot.org/uniprot/Q9D6X6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Secreted http://togogenome.org/gene/10090:Ap5s1 ^@ http://purl.uniprot.org/uniprot/Q9D742 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.|||Late endosome membrane|||Lysosome membrane|||Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1. Interacts with ZFYVE26 and SPG11 (By similarity).|||cytosol http://togogenome.org/gene/10090:Rara ^@ http://purl.uniprot.org/uniprot/P11416|||http://purl.uniprot.org/uniprot/Q3U3R3 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated; acetylation is increased upon pulsatile shear stress and decreased upon oscillatory shear stress.|||Belongs to the nuclear hormone receptor family. NR1 subfamily.|||By retinoic acid.|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Cytoplasm|||Expressed in Sertoli cells and germ cells.|||Heterodimer; with RXRA (PubMed:17205979). Binds DNA preferentially as a heterodimer (By similarity). RXRA serves as enhancer to induce RARA binding to RARE (By similarity). Interacts with RXRG (By similarity). Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes (PubMed:10788465, PubMed:9192892). Interacts with NCOA7; the interaction requires ligand-binding (By similarity). Interacts (via the ligand-binding domain) with PRAME; interaction is direct and ligand (retinoic acid)-dependent (By similarity). Interacts with PRKAR1A; the interaction negatively regulates RARA transcriptional activity (By similarity). Interacts with NCOR1; the interaction occurs in the absence of ligand and represses transcriptional activity (PubMed:17205979). Interacts with NCOR2 (By similarity). Interacts with PRMT2 (By similarity). Interacts with LRIF1 (By similarity). Interacts with ASXL1 and NCOA1 (By similarity). Interacts with ACTN4 (By similarity). Interacts with CDK7; the interaction is enhanced by interaction with GTF2H3 (PubMed:9230306). Interacts with GTF2H3; the interaction requires prior phosphorylation on Ser-369 which then enhances interaction with CDK7 (PubMed:19078967). In a complex with HDAC3, HDAC5 and HDAC7; the HDACs serve as corepressors of RARA, causing its deacetylation and inhibition of RARE DNA element binding; association with HDAC3, HDAC5 and HDAC7 is increased upon oscillatory shear stress (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).|||Nucleus|||Phosphorylated on serine and threonine residues. Phosphorylation does not change during cell cycle. Phosphorylation on Ser-77 is crucial for the N-terminal AF1 transcriptional activity. Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation. Phosphorylation by AKT1 inhibits the transactivation activity. On retinoic acid stimulation, phosphorylation on Ser-369 by RPS6KA5 promotes interaction with GTF2H3 and the CDK7-mediated phosphorylation of Ser-77.|||Receptor for retinoic acid (PubMed:17205979). Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes (PubMed:17205979). The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (PubMed:17205979). In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression (By similarity). On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation (PubMed:17205979, PubMed:9230306, PubMed:19078967). Formation of heterocomplex with histone deacetylases might lead to inhibition of RARE DNA element binding and to transcriptional repression (By similarity). Transcriptional activation and RARE DNA element binding might be supported by the transcription factor KLF2 (By similarity). RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis (PubMed:15901285). Has a role in the survival of early spermatocytes at the beginning prophase of meiosis (PubMed:15901285, PubMed:17905941). In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes (PubMed:10660575, PubMed:17905941). In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (PubMed:19389355). Together with RXRA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells (By similarity). In association with HDAC3, HDAC5 and HDAC7 corepressors, plays a role in the repression of microRNA-10a and thereby promotes the inflammatory response (By similarity).|||Seminiferous tubules of 6 month-old animals display varying degrees of testicular degeneration, with moderate to severe levels of germ-cell degeneration. Epithelial cells in the epididymis show general disorganization. Sperm count is reduced to about 1.7% of wild-type and sperm mobility reduced by half. Rara and Rarg, but not Rara and Rarb, double knockout mice exhibit growth retardation after 3 weeks. Defects are found in the growth plates with deficiency in cartilage. Growth retardation was noticable in limb sketal elements such as femurs. Early lethality and male sterility due to squamous metaplasia of the seminal vesicles and prostate are also observed.|||Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding. On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171. Probably desumoylated by SENP6. Sumoylation levels determine nuclear localization and regulate ATRA-mediated transcriptional activity (By similarity).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. http://togogenome.org/gene/10090:Rundc1 ^@ http://purl.uniprot.org/uniprot/Q0VDN7 ^@ Function ^@ May play a role as p53/TP53 inhibitor and thus may have oncogenic activity. http://togogenome.org/gene/10090:Sox5 ^@ http://purl.uniprot.org/uniprot/P35710 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed during spermatogenesis.|||Expressed in chondrocytes and, to a lesser extent, in brain.|||Expressed in the embryo and in adult testis.|||Expression is dependent on SOX9.|||Expression is transiently increased during brown adipocyte differentiation.|||Forms homodimers and heterodimers with SOX6.|||Newborn mice display mild skeletal abnormalities (PubMed:11702786). Mice lacking both Sox5 and Sox6 develop a severe chondrodysplasia characterized by the virtual absence of cartilage: chondrogenic cells are largely arrested at the stage of chondrogenic mesenchymal condensations (PubMed:11702786). Embryos lacking Sox5 (homozygous knockout) and heterozygous for Sox6 live until birth and show severe growth plate chondrocyte defects (PubMed:14993235). Embryos lacking Sox6 (homozygous knockout) and heterozygous for Sox5 live until birth and show severe growth plate chondrocyte defects (PubMed:14993235).|||Nucleus|||Testis-specific.|||Transcription factor involved in chondrocytes differentiation and cartilage formation (PubMed:1396566, PubMed:11702786, PubMed:8078769, PubMed:15529345, PubMed:14993235). Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including cartilage matrix protein-coding genes, such as COL2A1 and AGC1 (PubMed:9755172, PubMed:11702786, PubMed:26150426). Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: SOX5 and SOX6 cooperatively bind with SOX9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate SOX9's ability to transactivate (PubMed:11702786, PubMed:15529345, PubMed:14993235, PubMed:26150426). Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes (PubMed:14993235). Together with SOX6, required to form and maintain a pool of highly proliferating chondroblasts between epiphyses and metaphyses, to form columnar chondroblasts, delay chondrocyte prehypertrophy but promote hypertrophy, and to delay terminal differentiation of chondrocytes on contact with ossification fronts (PubMed:14993235). Binds to the proximal promoter region of the myelin protein MPZ gene (PubMed:26525805). http://togogenome.org/gene/10090:Elf1 ^@ http://purl.uniprot.org/uniprot/A0A2I3BPX9|||http://purl.uniprot.org/uniprot/Q3UQ47|||http://purl.uniprot.org/uniprot/Q3V1H4|||http://purl.uniprot.org/uniprot/Q60775 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Binds to the underphosphorylated form of RB. May interact with other transcription factors in order to regulate specific genes. Interacts with RUNX1. Interacts with SP1; the interaction is inhibited by glycosylation of SP1 (By similarity).|||Nucleus|||Predominantly found in hematopoietic cells. Detected in other cell types such as fibroblasts.|||Transcription factor that activates the LYN and BLK promoters. http://togogenome.org/gene/10090:Ranbp3 ^@ http://purl.uniprot.org/uniprot/Q9CT10 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP prevents binding of XPO1/CRM1 to the nuclear pore complex. Binds to CHC1/RCC1 and increases the guanine nucleotide exchange activity of CHC1/RCC1. Recruits XPO1/CRM1 to CHC1/RCC1 in a Ran-dependent manner. Negative regulator of TGF-beta signaling through interaction with the R-SMAD proteins, SMAD2 and SMAD3, and mediating their nuclear export (By similarity).|||Cytoplasm|||Interacts with CHC1 in a Ran-stimulated manner. Interacts with XPO1. Interacts (via its C-terminal R domain) with SMAD2 (dephosphorylated form via its MH1 and MH2 domains); the interaction results in the nuclear export of SMAD2 and termination of the TGF-beta signaling. Interacts (via its C-terminal R domain) with SMAD3 (dephosphorylated form via its MH1 domain); the interaction results in the nuclear export of SMAD3 and termination of the TGF-beta signaling (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ppp1r8 ^@ http://purl.uniprot.org/uniprot/Q8R3G1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Has a basic N- and C-terminal and an acidic central domain.|||Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Essential for cell proliferation and early embryonic development.|||Interacts with phosphorylated CDC5L, SF3B1 and MELK. Part of the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC (By similarity). Interacts with EED. Part of a complex consisting of PPP1R8, EED, HDAC2 and PP-1.|||May be inactivated by phosphorylation on Ser-199 or Ser-204.|||Mice display a retarded growth and embryonic lethality at E6.5, due to defects in proliferation rate.|||Nucleus|||Nucleus speckle|||The FHA domain mediates interactions with threonine-phosphorylated MELK. http://togogenome.org/gene/10090:Vat1 ^@ http://purl.uniprot.org/uniprot/Q499X4|||http://purl.uniprot.org/uniprot/Q62465 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.|||Cytoplasm|||Mitochondrion outer membrane|||Plays a part in calcium-regulated keratinocyte activation in epidermal repair mechanisms. Has no effect on cell proliferation (By similarity). Possesses ATPase activity. Negatively regulates mitochondrial fusion in cooperation with mitofusin proteins (MFN1-2) (By similarity). http://togogenome.org/gene/10090:Tnfrsf13c ^@ http://purl.uniprot.org/uniprot/Q9D8D0 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response.|||Defects in Tnfrsf13c are a cause of severe B-cell deficiency. B-cell deficient strain A/WySnJ has a 4.7 kb insertion in the BAFFR gene leading to an altered C-terminus. The mutant RNA is not detectable. B-cell lymphopoiesis is normal, but the life span of peripheral B-cells is much reduced.|||Highly expressed in spleen and testis; detected at lower levels in lung and thymus.|||Membrane http://togogenome.org/gene/10090:Hoxb5 ^@ http://purl.uniprot.org/uniprot/P09079 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Antp homeobox family.|||Embryo.|||Expressed in a broad spectrum of tissues.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Crh ^@ http://purl.uniprot.org/uniprot/Q8CIT0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.|||Expressed in parvocellular paraventricular nucleus of the hypothalamus and in medial accessory olivary nucleus.|||Hormone regulating the release of corticotropin from pituitary gland. Induces NLRP6 in intestinal epithelial cells, hence may influence gut microbiota profile (PubMed:23470617).|||Interacts (via C-terminus) with CRFR1 (via N-terminal extracellular domain).|||Secreted|||Up-regulated during water-avoidance stress. http://togogenome.org/gene/10090:Rftn2 ^@ http://purl.uniprot.org/uniprot/Q8CHX7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the raftlin family.|||Cell membrane|||Double RFTN1 and RFTN2 mutant mice show no visible phenotype under pathogen-free conditions but show greatly reduced interferon beta production in splenic dendritic cells under poly(I:C) or lipopolysaccharide stimulation.|||Expressed in B-cells, heart, brain, spleen, large intestine and lung (PubMed:19414744). Expressed in dendritic cells and macrophages (PubMed:27022195).|||Upon bacterial lipopolysaccharide stimulation, mediates clathrin-dependent internalization of TLR4 in dendritic cells, resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production (PubMed:27022195). May regulate B-cell antigen receptor-mediated signaling. http://togogenome.org/gene/10090:Vti1a ^@ http://purl.uniprot.org/uniprot/O89116|||http://purl.uniprot.org/uniprot/Q5FWJ7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the VTI1 family.|||Golgi apparatus membrane|||Interacts with distinct SNARE complexes that contain either STX5 or STX6. Interacts with NAPA and, to a lesser extent, with NAPG. Identified in a complex containing STX6, STX12, VAMP4 and VTI1A (By similarity).|||Membrane|||V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane. These interactions are proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. Involved in vesicular transport from the late endosomes to the trans-Golgi network. Along with VAMP7, involved in an non-conventional RAB1-dependent traffic route to the cell surface used by KCNIP1 and KCND2. May be concerned with increased secretion of cytokines associated with cellular senescence.|||Widely expressed. http://togogenome.org/gene/10090:Tnrc6b ^@ http://purl.uniprot.org/uniprot/Q8BKI2|||http://purl.uniprot.org/uniprot/Q8BWL0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GW182 family.|||Interacts with AGO1, AGO2, AGO3 and AGO4. Interacts with CNOT1; the interaction mediates the association with the CCR4-NOT complex. Interacts with PAN3; the interaction mediates the association with the PAN complex. Interacts with MOV10; the interaction is direct and RNA-dependent.|||P-body|||Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes. http://togogenome.org/gene/10090:Fga ^@ http://purl.uniprot.org/uniprot/E9PV24 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure.|||Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots (PubMed:7649481). In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization (PubMed:11389004). Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood (PubMed:7649481). However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo (PubMed:10930441). Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway (PubMed:19332769). Maternal fibrinogen is essential for successful pregnancy (PubMed:7649481). Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage (PubMed:12629066). May also facilitate the immune response via both innate and T-cell mediated pathways (PubMed:23487423).|||Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers.|||Expressed in liver.|||Forms F13A-mediated cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming fibronectin-fibrinogen heteropolymers.|||Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain.|||Knockout mice are viable but only males are fertile (PubMed:7649481). Neonates frequently develop spontaneous hemorrhages, but in spite of this over 90% of mice survive the neonatal period (PubMed:7649481). However only half survive beyond 70 days of age; lethality is most often due to intra-abdominal hemorrhage (PubMed:7649481). Pregnancy in female mice fails at around 10 days of gestation, associated with severe intrauterine bleeding (PubMed:7649481). Secondary loss of FGB and FGG from circulating blood is observed, although FGB and FGG mRNA is normally expressed in hepatocytes (thought to be the main site of fibrinogen synthesis) (PubMed:7649481). In vitro, blood fails to clot and platelet aggregations do not form (PubMed:7649481). In vivo, platelet aggregation in injured arterioles initially occurs normally although thrombi are unstable and readily embolize (PubMed:10930441). In double knockouts of FGA and VWF, platelet aggregation is delayed and thrombi frequently embolize (PubMed:10930441). Mice succumb more rapidly to Y. pestis infection, associated with increased bacterial loads in liver and lung; however induction of the inflammatory response factors TNF, IFNG, CXCL1, and LCN2 is not affected (PubMed:23487423). Mice succumb more rapidly to T. gondii infection, with increased hemorrhagic pathology; however parasite numbers are not significantly increased and induction of the inflammatory response markers IL12, IFNG, TNF, IL10, and nitric oxide is not affected (PubMed:12629066). Mice succumb more rapidly to L. monocytogenes infection, with increased hemorrhagic pathology and increased bacterial burdens in hepatic tissue; however there is little effect on peritoneal bacterial numbers or bacterial dissemination to other tissues, and also no effect on induction of the inflammatory markers IFNG, TNF and NOS2 (PubMed:15972474).|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Fndc4 ^@ http://purl.uniprot.org/uniprot/Q3TR08 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an anti-inflammatory factor in the intestine and colon. Binds to and acts on macrophages to down-regulate pro-inflammatory gene expression. Affects key macrophage functions, including phagocytosis, by down-regulating many key pathways for macrophage activation, partly via by STAT3 activation and signaling. May be required to dampen the immunological response in colitis.|||During embryo development, expressed in the brain.|||Highly expressed in adult liver and brain tissues.|||Membrane|||Secreted|||Therapeutic delivery of FNDC4 reduces the disease severity of chemical-induced colitis in mice.|||Up-regulated in the context of tissue inflammation. http://togogenome.org/gene/10090:Clec16a ^@ http://purl.uniprot.org/uniprot/Q80U30 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CLEC16A/gop-1 family.|||Endosome membrane|||Interacts with RNF41/NRDP1.|||Lysosome membrane|||Mice with pancreatic specific deletion of Clec16a are significantly hyperglycemic and have reduced basal and blunted insulin release after glucose administration. Mutant mice have normal islet architecture and beta cell mass, but beta cells show accumulation of vacuolated structures and unhealthy mitochondria (rounded mitochondria with disordered and amorphous structure). Not associated with immune infiltration and insulitis.|||Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway. Mitophagy is a selective form of autophagy necessary for mitochondrial quality control. The RNF41/NRDP1-PRKN pathway regulates autophagosome-lysosome fusion during late mitophagy. May protect RNF41/NRDP1 from proteasomal degradation, RNF41/NRDP1 which regulates proteasomal degradation of PRKN. Plays a key role in beta cells functions by regulating mitophagy/autophagy and mitochondrial health.|||Ubiquitously expressed. Expressed in pancreatic islets. http://togogenome.org/gene/10090:Synj2bp ^@ http://purl.uniprot.org/uniprot/Q9D6K5 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds (via the PDZ domain) to isoform 2A of SYNJ2 (via the unique motif in the C-terminus) (By similarity). Interacts (via C-terminus) with RALBP1. Interacts (via PDZ domain) with ACVR2A (via C-terminus) and ACVR2B (via C-terminus). Forms a ternary complex with ACVR2A and RALBP1 (PubMed:11882656, PubMed:16648306). Interacts with MAPK12 (By similarity). Interacts with DLL1; enhances DLL1 protein stability, and promotes notch signaling in endothelial cells (By similarity).|||Isoform 1 and isoform 2 are widely expressed, notably in brain, heart, lung, liver, kidney, skeletal muscle, ovary and testis. Isoform 3 is detected only in heart, spleen and testis.|||Isoform 1 regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Isoform 2 and isoform 3 show a stimulatory affect on activin-induced signal transduction and enhance activin type 2 expression at the cell surface.|||Mitochondrion outer membrane|||Up-regulated between 12 and 24 hours after treatment with activin A and lipopolysaccharide (LPS). Down-regulated by calcium ionophore A23187.|||perinuclear region http://togogenome.org/gene/10090:Ptgs1 ^@ http://purl.uniprot.org/uniprot/P22437|||http://purl.uniprot.org/uniprot/Q543T1 ^@ Activity Regulation|||Caution|||Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prostaglandin G/H synthase family.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.|||Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PTGS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PTGS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.|||Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products.|||Endoplasmic reticulum membrane|||Homodimer.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Microsome membrane|||PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.|||The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.|||The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac and diclofenac. http://togogenome.org/gene/10090:Star ^@ http://purl.uniprot.org/uniprot/P51557 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed within glia and neurons in discrete regions of the brain.|||May interact with TSPO.|||Mitochondrion|||Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Transporter that binds to and transport cholesterol through the intermembrane space of the mitochondrion. http://togogenome.org/gene/10090:Il19 ^@ http://purl.uniprot.org/uniprot/Q14BK1|||http://purl.uniprot.org/uniprot/Q8CJ70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-10 family.|||Cytokine that functions as an anti-inflammatory and proangiogenic factor (PubMed:12370360, PubMed:27053520). Polarizes adaptive immunity to an anti-inflammatory phenotype through induction of T-helper 2 responses by both down-regulation of IFN-gamma and up-regulation of IL4 and IL5 (PubMed:15557163). Produced by osteocytes, stimulates granulopoiesis and neutrophil formation (PubMed:33684929). Exerts its biological effect through a receptor complex consisting of a heterodimer of IL20RA and IL20RB. In turn, activates the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway, and importantly, STAT3 (By similarity).|||IL19-deficient mice are more susceptible to innate-mediated colitis and develop more severe inflammation in response to injury (PubMed:19834971). In addition, mice respond to vascular endothelial growth factor (VEGF) significantly less than wild-type mice (PubMed:27053520).|||Immune regulatory cytokine.|||Secreted http://togogenome.org/gene/10090:Adarb1 ^@ http://purl.uniprot.org/uniprot/Q91ZS8 ^@ Cofactor|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.|||Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can inhibit cell proliferation and migration and can stimulate exocytosis.|||Homodimer. Homodimerization is essential for its catalytic activity. Can form heterodimers with isoform 5 of ADAR/ADAR1 (By similarity).|||Likely expressed from an alternative promoter. Contains a region highly similar to the so-called ssRNA-binding R-domain of ADARB2.|||Nucleus|||nucleolus http://togogenome.org/gene/10090:Vmn2r12 ^@ http://purl.uniprot.org/uniprot/L7N217 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rbms1 ^@ http://purl.uniprot.org/uniprot/Q91W59 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||Single-stranded DNA binding protein that interacts with the region upstream of the MYC gene. Binds specifically to the DNA sequence motif 5'-[AT]CT[AT][AT]T-3'. Probably has a role in DNA replication.|||Ubiquitous. Expressed in all tissues except testis. http://togogenome.org/gene/10090:Ypel3 ^@ http://purl.uniprot.org/uniprot/P61237 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the yippee family.|||Involved in proliferation and apoptosis in myeloid precursor cells.|||Probably ubiquitinated leading to its degradation by the proteasome.|||Up-regulated after the removal of interleukin 3 and exposure to granulocyte colony stimulating factor.|||Widely expressed. Strongly expressed in heart, brain, testis, lung, spleen, liver, kidney and myeloid cells.|||nucleolus http://togogenome.org/gene/10090:Zic3 ^@ http://purl.uniprot.org/uniprot/Q62521 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.|||Belongs to the GLI C2H2-type zinc-finger protein family.|||CNS. A high level expression is seen in the cerebellum.|||Cytoplasm|||Expressed in the CNS, tailbud and somites.|||Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity (By similarity). Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity.|||Nucleus|||Some mice exhibit embryonic and postnatal lethality. Viable mice show heart disease, disturbances of laterality, neural tube defects and vertebral and rib defects.|||The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation. http://togogenome.org/gene/10090:Ilf3 ^@ http://purl.uniprot.org/uniprot/A0A1L1STE4|||http://purl.uniprot.org/uniprot/Q45VK5|||http://purl.uniprot.org/uniprot/Q45VK6|||http://purl.uniprot.org/uniprot/Q9Z1X4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with FUS and SMN. Interacts (via C-terminus) with PRMT1. Forms a complex with ILF2. Can also bind to PRKDC/XRCC7: this may stabilize the interaction of PRKDC/XRCC7 and the heterodimeric complex of XRCC6/KU70 and XRCC5/KU80. Forms a heteromeric complex with ZNF346 and ILF3. Found in a nuclear export complex with XPO5, ILF3, Ran and double-stranded RNA or double-stranded minihelix VA1 RNA. Found in a nuclear export complex with XPO5, RAN, ILF3, ZNF346 and double-stranded RNA. Interacts with XPO5 and ZNF346. Forms a complex with ILF2, YLPM1, KHDRBS1, RBMX, NCOA5 and PPP1CA. Interacts with AGO1 and AGO2. Interacts with DHX36; this interaction occurs in a RNA-dependent manner. Interacts with ELAVL1; this interaction occurs in a RNA-dependent manner. Interacts with HAVCR2; this interaction promotes ILF3 ubiquitination and subsequent degradation (By similarity).|||Methylated by protein arginine N-methyltransferase 1.|||Nucleus|||Phosphorylated at Thr-188 and Thr-315 by PKR in response to RNA viruses. This phosphorylation results in the dissociation of ILF2 from the ILF2-ILF3 complex resulting in a cytoplasmic sequestration of ILF3 where it can bind to viral RNAs and impede viral replication.|||RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs. As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response. Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs.|||Ubiquitous. Expressed at high levels in the thymus, testis, ovary and at lower levelss in the spleen.|||nucleolus http://togogenome.org/gene/10090:Pigr ^@ http://purl.uniprot.org/uniprot/O70570 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Either free or part of the secretory IgA (sIgA) complex that consists of two, four or five IgA monomers, and two additional non-Ig polypeptides, namely the JCHAIN and the secretory component (the proteolytic product of PIGR). Free secretory component interacts with bacterial antigens toxA of C. difficile and eae of E. coli.|||Interacts (mainly via CDR1-like domain) with dimeric IgA. Interacts (mainly via CDR2-like domain) with pentameric IgM.|||Mediates selective transcytosis of polymeric IgA and IgM across mucosal epithelial cells. Binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process, a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment.|||N-glycosylated. N-glycosylation is required for anchoring IgA molecules to mucus, but is not necessary for Ig binding.|||Secreted|||The Ig-like V-type 1/D1 domain contains three complementarity determining region-like loops CDR1-3, which mediate interaction with IgA and IgM.|||Through its N-linked glycans ensures anchoring of secretory IgA (sIgA) molecules to mucus lining the epithelial surface to neutralize extracellular pathogens. On its own (free form) may act as a non-specific microbial scavenger to prevent pathogen interaction with epithelial cells. http://togogenome.org/gene/10090:Gnb3 ^@ http://purl.uniprot.org/uniprot/Q54AE3|||http://purl.uniprot.org/uniprot/Q61011 ^@ Function|||Similarity|||Subunit ^@ Belongs to the WD repeat G protein beta family.|||G proteins are composed of 3 units, alpha, beta and gamma. Interacts with RASD2 (By similarity).|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Rabgap1 ^@ http://purl.uniprot.org/uniprot/A2AWA9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with RAB6A and tubulin gamma.|||May act as a GTPase-activating protein of RAB6A. May play a role in microtubule nucleation by centrosome. May participate in a RAB6A-mediated pathway involved in the metaphase-anaphase transition (By similarity).|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.|||centrosome|||cytosol http://togogenome.org/gene/10090:Gpr12 ^@ http://purl.uniprot.org/uniprot/P35412 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed predominantly in the forebrain and a lesser extent in the hindbrain. Lower expression in the liver.|||Receptor with constitutive G(s) signaling activity that stimulates cyclic AMP production (By similarity). Promotes neurite outgrowth and blocks myelin inhibition in neurons.|||Was originally thought to be a receptor for sphingosine 1-phosphate. http://togogenome.org/gene/10090:Tyw5 ^@ http://purl.uniprot.org/uniprot/A2RSX7 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the TYW5 family.|||Binds 1 Fe(2+) ion per subunit.|||Homodimer.|||tRNA hydroxylase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the hydroxylation of 7-(a-amino-a-carboxypropyl)wyosine (yW-72) into undermodified hydroxywybutosine (OHyW*). OHyW* being further transformed into hydroxywybutosine (OHyW) by LCMT2/TYW4. OHyW is a derivative of wybutosine found in higher eukaryotes. http://togogenome.org/gene/10090:Paxx ^@ http://purl.uniprot.org/uniprot/Q8K0Y7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the XRCC4-XLF family. PAXX subfamily.|||Chromosome|||Homodimer (By similarity). Interacts with the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer (Ku complex); the interaction is direct (By similarity). Associated component of the non-homologous end joining (NHEJ) complex, composed of the core proteins PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). Interacts with POLL (DNA polymerase lambda); promoting POLL recruitment to double-strand breaks (DSBs) and stimulation of the end-filling activity of POLL (By similarity).|||No visible phenotype in normal conditions (PubMed:27798842, PubMed:28051062, PubMed:29511619, PubMed:29511621). Mice are viable, grow normally, are fertile and have normal lymphocyte development (PubMed:27798842, PubMed:29511619, PubMed:29511621). They however show mild radiosensitivity (PubMed:29511619, PubMed:29511621). Mice lacking both Paxx and Nhej1/Xlf show embryonic lethality caused by severe defects in classical non-homologous end joining (NHEJ) (PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092).|||Non-essential DNA repair protein involved in DNA non-homologous end joining (NHEJ); participates in double-strand break (DSB) repair and V(D)J recombination (PubMed:27601299, PubMed:27798842, PubMed:27601633, PubMed:27830975, PubMed:28051062, PubMed:29077092). May act as a scaffold required for accumulation of the Ku heterodimer, composed of XRCC5/Ku80 and XRCC6/Ku70, at double-strand break sites and promote the assembly and/or stability of the NHEJ machinery (PubMed:28051062). Involved in NHEJ by promoting the ligation of blunt-ended DNA ends (By similarity). Together with NHEJ1/XLF, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (By similarity). Constitutes a non-essential component of classical NHEJ: has a complementary but distinct function with NHEJ1/XLF in DNA repair (PubMed:27601299, PubMed:27798842, PubMed:27830975, PubMed:28051062).|||Nucleus|||Phosphorylation may inhibit interaction with the DNA-bound XRCC5/Ku80 and XRCC6/Ku70 heterodimer (Ku complex).|||The N-terminus (residues 1-115) forms a head domain that is structurally related to those of XRCC4, XLF/NHEJ1, and SASS6. http://togogenome.org/gene/10090:Sfxn3 ^@ http://purl.uniprot.org/uniprot/Q3U4F0|||http://purl.uniprot.org/uniprot/Q91V61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sideroflexin family.|||Membrane|||Mitochondrial serine transporter that mediates transport of serine into mitochondria, an important step of the one-carbon metabolism pathway. Mitochondrial serine is converted to glycine and formate, which then exits to the cytosol where it is used to generate the charged folates that serve as one-carbon donors.|||Mitochondrion membrane|||Widely expressed. http://togogenome.org/gene/10090:Glrx ^@ http://purl.uniprot.org/uniprot/Q3U6L3|||http://purl.uniprot.org/uniprot/Q9QUH0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glutaredoxin family.|||Cytoplasm|||Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins. http://togogenome.org/gene/10090:Sirpa ^@ http://purl.uniprot.org/uniprot/P97797 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds PTPN11 when tyrosine-phosphorylated, except in macrophages, where it primarily binds PTPN6. Binds GRB2 vitro. Binds FGR. Binds JAK2 irrespective of its phosphorylation status and forms a stable complex. Binds SCAP1 and/or SCAP2. The resulting complex recruits FYB1. Binds PTK2B (By similarity). Interacts with TRIM2 (PubMed:30726215).|||Highly expressed in cerebral cortex, brain, spinal cord, cerebellum and spleen, and at much lower levels in kidney, thymus, heart, lung and liver. Within the cerebellum, highly expressed throughout the molecular layer, and in synaptic glomeruli in the granule cell layer. Detected in neurons of the hippocampus and dentate gyrus, and in olfactory bulb. Not detected in Purkinje cells. Highly expressed in the plexiform layers, optic fiber layer and the outer segments of the photoreceptor layer in the retina. Highly expressed in macrophages. Isoform 3 is detected at very low levels in all tissues tested.|||Highly expressed in the CNS of embryos from day 7 to 17.|||Immunoglobulin-like cell surface receptor for CD47 (PubMed:18045614). Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function. Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells (By similarity). Plays a role in antiviral immunity and limits new world arenavirus infection by decreasing virus internalization (PubMed:30726215). Receptor for THBS1 (By similarity). Interaction with THBS1 stimulates phosphorylation of SIRPA (By similarity). In response to THBS1, involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production (By similarity).|||Membrane|||N-glycosylated.|||Phosphorylated on tyrosine residues. http://togogenome.org/gene/10090:Pcmt1 ^@ http://purl.uniprot.org/uniprot/E0CYV0|||http://purl.uniprot.org/uniprot/E9PWE0|||http://purl.uniprot.org/uniprot/P23506|||http://purl.uniprot.org/uniprot/Q545L9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.|||Initiates the repair of damaged proteins by catalyzing methyl esterification of L-isoaspartyl and D-aspartyl residues produced by spontaneous isomerization and racemization of L-aspartyl and L-asparaginyl residues in aging peptides and proteins (PubMed:12023972, PubMed:16923807, PubMed:20424163). Acts on EIF4EBP2, microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin C-terminal hydrolase isozyme L1, phosphatidylethanolamine-binding protein 1, stathmin, beta-synuclein and alpha-synuclein (PubMed:16923807, PubMed:20424163).|||Monomer.|||The survival of Pcmt1 homozygous knockout mice drops significantly between the ages of 20 and 50 days compared to their wild-type counterparts (PubMed:12023972). They have 20 times more damaged aspartyl residues in their brains (PubMed:12023972).|||cytosol http://togogenome.org/gene/10090:Vmn2r17 ^@ http://purl.uniprot.org/uniprot/E9PYF5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc25a46 ^@ http://purl.uniprot.org/uniprot/Q9CQS4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex. May associate with the endoplasmic reticulum membrane protein complex (EMC).|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrion outer membrane|||Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization. May regulate the assembly of the MICOS (mitochondrial contact site and cristae organizing system) complex which is essential to the biogenesis and dynamics of mitochondrial cristae, the inwards folds of the inner mitochondrial membrane. Through its interaction with the EMC (endoplasmic reticulum membrane protein complex), could regulate mitochondrial lipid homeostasis and thereby mitochondrial fission. http://togogenome.org/gene/10090:Ptprb ^@ http://purl.uniprot.org/uniprot/A0A1W2P7W3|||http://purl.uniprot.org/uniprot/B2RU80 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.|||Expressed in both arterial and venous vascular endothelium in embryos, although more strongly in arterial vessels. Highly expressed in the developing outflow tract of the heart and later is expressed in developing heart valves.|||Expression is very high in the vasculature of lung, spleen, and kidney, as well as in the heart valves, and is also present in the endothelium of arterioles and venules. Also expressed in tumor vasculature.|||Membrane|||Mice show severe cardiovascular defects and embryonic lethality by 10 dpc. Vasculogenesis occurs normally however, angiogenesis is abnormal. Angiogenic defects are most pronounced in the yolk sac and include a complete failure to elaborate the primitive vascular scaffold into higher-order branched arteries, veins, and capillaries.|||Monomer (By similarity). Interacts with TEK (PubMed:10557082, PubMed:19451274). Interacts via fibronectin type-III 17 domain with CDH5 (PubMed:19015309). Detected in a complex with CNTN1 and NRCAM (PubMed:11564762). Interacts (phosphorylated form) with FYN and GRB2 (PubMed:20398064).|||Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin. http://togogenome.org/gene/10090:Trpm6 ^@ http://purl.uniprot.org/uniprot/A0A1W5LU38|||http://purl.uniprot.org/uniprot/Q8CIR4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Essential ion channel and kinase. Crucial for magnesium homeostasis. Has an important role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney (By similarity).|||Forms heterodimers with TRPM7. Interacts (via kinase domain) with RACK1 (By similarity).|||In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.|||In the N-terminal section; belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM6 sub-subfamily.|||Membrane http://togogenome.org/gene/10090:Mertk ^@ http://purl.uniprot.org/uniprot/Q60805 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on Tyr-744, Tyr-748 and Tyr-749 in the activation loop allowing full activity (By similarity). Autophosphorylated on Tyr-867 leading to recruitment of downstream partners of the signaling cascade such as PLCG2.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.|||Cell membrane|||Expressed during most, if not all, stages of embryological development beginning in the morula and blastocyst and progressing through the yolk sac and fetal liver stages.|||Expressed predominantly in the hematopoietic lineages: macrophages, NK cells, NKT cells, dendritic cells and platelets.|||Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation. Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6. Interacts with VAV1 in a phosphotyrosine-independent manner. Interacts with TIMD4; this interaction enhances TIMD4-mediated efferocytosis (By similarity).|||Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.|||knockout mice are fertile, but male animals that lack all three receptors TYRO3, AXL and MERTK produce no mature sperm. http://togogenome.org/gene/10090:Ubl4a ^@ http://purl.uniprot.org/uniprot/P21126|||http://purl.uniprot.org/uniprot/Q3UK94 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome.|||Component of the BAG6/BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with BAG6; the interaction is direct and required for UBL4A protein stability. Interacts with USP13; may be indirect via BAG6.|||Nucleus|||Polyubiquitinated. Ubiquitination by AMFR and deubiquitination by USP13 may regulate the interaction between the BAG6/BAT3 complex and SGTA and therefore may regulate client proteins fate.|||cytosol http://togogenome.org/gene/10090:Taf10 ^@ http://purl.uniprot.org/uniprot/Q8K0H5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF10 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the TATA-binding protein-free TAF complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. The PCAF complex consists at least of TADA2L/ADA2, TADA3L/ADA3, SUPT3H, TAF5L TAF6L, TAF9, TAF10, TAF12 and TRRAP. The TFTC-HAT complex consists at least of TAF5L, TAF6L, TADA3L, SUPT3H, TAF2, TAF4, TAF5, GCN5L2/GCN5, TAF10 and TRRAP. The STAGA transcription coactivator-HAT complex consists at least of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. The STAGA core complex is associated with a subcomplex required for histone deubiquitination composed of ATXN7L3, ENY2 and USP22. Interacts with LOXL2. Interacts with TAF12 isoform TAFII20; the interaction is direct (By similarity). Interacts with TAF3 (PubMed:11438666).|||Lysine deamination at Lys-189 to form allysine is mediated by LOXL2. Allysine formation by LOXL2 results in release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription.|||Monomethylated at Lys-189 by SETD7, leading to increased affinity for RNA polymerase II.|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. TAF10 is also component of the PCAF histone acetylase complex, the TATA-binding protein-free TAF complex (TFTC) and the STAGA transcription coactivator-HAT complex (By similarity). May regulate cyclin E expression (PubMed:10469660).|||The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase. http://togogenome.org/gene/10090:Ndufa9 ^@ http://purl.uniprot.org/uniprot/Q9DC69 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Acetylated on lysine residues. BLOC1S1 is required for acetylation. Acetylated by CLOCK in a circadian manner.|||Belongs to the complex I NDUFA9 subunit family.|||Binds 1 FAD per subunit.|||Complex I is composed of 45 different subunits (By similarity). This a component of the hydrophobic protein fraction (By similarity). Interacts with BLOC1S1 (By similarity). Interacts with SLC2A4 (By similarity). Interacts with CLOCK (By similarity). Interacts with RAB5IF (PubMed:31536960).|||Mitochondrion matrix http://togogenome.org/gene/10090:Rreb1 ^@ http://purl.uniprot.org/uniprot/Q3UH06 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in splenic B-cells.|||Interacts with NEUROD1 (By similarity). Interacts with AR (By similarity).|||Nucleus speckle|||Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters (PubMed:12700664). Represses the angiotensinogen gene (By similarity). Negatively regulates the transcriptional activity of AR (By similarity). Potentiates the transcriptional activity of NEUROD1 (By similarity). Binds specifically to the allelic variant of the CDKN2A promoter present in Balb/c mice, which leads to a down-regulation of CDKN2A expression in this strain, and, as a consequence, to an elevated susceptibility to pristane-induced tumors (PubMed:12700664). Promotes brown adipocyte differentiation (PubMed:27923061). May be involved in Ras/Raf-mediated cell differentiation by enhancing calcitonin expression (By similarity). http://togogenome.org/gene/10090:Rpl39 ^@ http://purl.uniprot.org/uniprot/P62892|||http://purl.uniprot.org/uniprot/Q505A8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL39 family.|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with IMPACT (PubMed:22404850).|||Cytoplasm|||RNA-binding component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:34428590, PubMed:36517592). http://togogenome.org/gene/10090:Atg2b ^@ http://purl.uniprot.org/uniprot/Q80XK6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATG2 family.|||Endoplasmic reticulum membrane|||Interacts with WDR45/WIPI4.|||Lipid droplet|||Lipid transfer protein required for both autophagosome formation and regulation of lipid droplet morphology and dispersion. Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion (By similarity). Binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, and extracts phospholipids from the membrane source and transfers them to ATG9 (ATG9A or ATG9B) to the IM for membrane expansion (By similarity). Lipid transfer activity is enhanced by WDR45/WIPI4, which promotes ATG2B-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (By similarity).|||Preautophagosomal structure membrane|||The chorein N-terminal domain mediates lipid transfer activity. http://togogenome.org/gene/10090:B2m ^@ http://purl.uniprot.org/uniprot/P01887 ^@ Function|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the beta-2-microglobulin family.|||Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.|||Heterodimer of an alpha chain and a beta chain. Beta-2-microglobulin is the beta-chain of major histocompatibility complex class I molecules. Forms a heterotrimer with MR1 and a metabolite antigen.|||Secreted|||The following alleles of B2M are known: A, B, W2, W3, W4 and W5 (C). The sequence shown is that of allele B. http://togogenome.org/gene/10090:Trpm3 ^@ http://purl.uniprot.org/uniprot/B2RUS0|||http://purl.uniprot.org/uniprot/D3Z539|||http://purl.uniprot.org/uniprot/E9PUC8|||http://purl.uniprot.org/uniprot/J9SVL3|||http://purl.uniprot.org/uniprot/Q5F4S6|||http://purl.uniprot.org/uniprot/Q5F4S7|||http://purl.uniprot.org/uniprot/Q5F4S8|||http://purl.uniprot.org/uniprot/Q5F4S9|||http://purl.uniprot.org/uniprot/Q5F4T0|||http://purl.uniprot.org/uniprot/Q69ZE8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rsl24d1 ^@ http://purl.uniprot.org/uniprot/Q5EBK7|||http://purl.uniprot.org/uniprot/Q99L28 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with nucleolar and cytoplasmic pre-60S particles (By similarity). At the end of biogenesis it dissociates from cytoplasmic pre-60S particles and is likely to be exchanged for its ribosomal homolog, RPL24 (By similarity).|||Belongs to the eukaryotic ribosomal protein eL24 family.|||Involved in the biogenesis of the 60S ribosomal subunit. Ensures the docking of GTPBP4/NOG1 to pre-60S particles (By similarity).|||nucleolus http://togogenome.org/gene/10090:Pik3c2b ^@ http://purl.uniprot.org/uniprot/E9QAN8 ^@ Similarity ^@ Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily. http://togogenome.org/gene/10090:Or2t46 ^@ http://purl.uniprot.org/uniprot/Q5NCD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Scyl1 ^@ http://purl.uniprot.org/uniprot/Q9EQC5 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Cytoplasm|||Defects in Scyl1 are the cause of the muscle deficient phenotype (mdf). Mice exhibit progressive neuromuscular atrophy, hindlimb paralysis, gait ataxia, abnormal hindlimb posture and tremor. Pathology of mdf comprises cerebellar atrophy, Purkinje cell loss and optic nerve atrophy.|||Endoplasmic reticulum-Golgi intermediate compartment|||Expressed in diaphragm, quadriceps, thymus, liver, lung, spleen, kidney, heart and brain. Prominently expressed in neurons, and enriched at central nervous system synapses and neuromuscular junctions.|||Homooligomer (By similarity). Interacts with GORAB. Interacts with COPA, COPB1 and COPB2. Interacts with AP2B1 (By similarity).|||Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum. Involved in the maintenance of the Golgi apparatus morphology. Has no detectable kinase activity in vitro.|||The protein kinase domain is predicted to be catalytically inactive.|||centrosome|||cis-Golgi network http://togogenome.org/gene/10090:Tmem89 ^@ http://purl.uniprot.org/uniprot/Q9DA04 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Impact ^@ http://purl.uniprot.org/uniprot/O55091 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IMPACT family.|||Cytoplasm|||Detected in embryos at 7, 11, 15, and 17 dpc. At 16 dpc, predominantly expressed in the central nervous system (at protein level). Strongly up-regulated during brain development from 17 dpc up to at least postnatal days 14 (at protein level). In N2a neuroblastoma cell line model and in primary cultures of hippocampal neurons, up-regulated during neuronal differentiation induced by serum reduction (at protein level).|||Interacts with GCN1; prevents the interaction of GCN1 with EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity (PubMed:15937339, PubMed:22404850). Interaction with RPL39; this interaction occurs in a GCN1-independent manner (PubMed:22404850). Associates with ribosomes; this interaction occurs in a GCN1-independent manner (PubMed:22404850). Associates with actin; this interaction occurs in a GCN1-independent manner (PubMed:22404850).|||Present in neurons in most areas of the brain. Present at high level in hypothalamus, particularly in the suprachiasmatic nucleus (at protein level) (PubMed:15937339, PubMed:18260151). Preferentially expressed in brain, with a weaker expression in other tissues (PubMed:9256468).|||The Impact locus is imprinted. Paternal inherited gene is expressed, while the maternal inherited gene is silenced. In contrast with most imprinted genes, neighboring genes are apparently not imprinted.|||Translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation. Plays a role as a negative regulator of the EIF2AK4/GCN2 kinase activity; impairs GCN1-mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis (PubMed:15937339, PubMed:23447528, PubMed:24333428). May be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis (PubMed:15937339, PubMed:23447528). Through its inhibitory action on EIF2AK4/GCN2, plays a role in differentiation of neuronal cells by stimulating neurite outgrowth (PubMed:23447528).|||Up-regulated after serum withdrawal during neuronal differentiation (PubMed:23447528). http://togogenome.org/gene/10090:Baiap3 ^@ http://purl.uniprot.org/uniprot/Q80TT2 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the unc-13 family.|||Binds 3 Ca(2+) ions per C2 domain.|||Cell membrane|||Functions in endosome to Golgi retrograde transport. In response to calcium influx, may interact with SNARE fusion receptors and membrane phospholipids to mediate endosome fusion with the trans-Golgi network. By promoting the recycling of secretory vesicle transmembrane proteins, it indirectly controls dense-core secretory vesicle biogenesis, maturation and their ability to mediate the constitutive and regulated secretion of neurotransmitters and hormones. May regulate behavior and food intake by controlling calcium-stimulated exocytosis of neurotransmitters including NPY and serotonin and hormones like insulin (By similarity). Proposed to play a role in hypothalamic neuronal firing by modulating gamma-aminobutyric acid (GABA)ergic inhibitory neurotransmission (Probable).|||Interacts with ADGRB1, this interaction is direct. Interacts with endosomal SNARE proteins VAMP3, VAMP4, STX6 and STX16; this interaction is increased in the presence of calcium.|||Late endosome membrane|||Mutant mice are viable, fertile and have overall normal development. Behavioral phenotyping show increased susceptibility to pentylenetetrazole-induced seizures, increased anxiety in females, and benzodiazepine tolerance in males.|||Prominently expressed in brain structures including hypothalamus, amygdala, stria terminalis and periaqueductal gray (at protein level). Expressed in nonneuronal tissues, including placenta, lung, pancreas, spleen, and testes. Within placenta, expression is restricted to the syncytiotrophoblasts.|||Recycling endosome membrane|||cytosol|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ufd1 ^@ http://purl.uniprot.org/uniprot/P70362 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UFD1 family.|||Essential component of the ubiquitin-dependent proteolytic pathway which degrades ubiquitin fusion proteins. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. It may be involved in the development of some ectoderm-derived structures (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and NPLOC4, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (By similarity).|||Expressed at high levels in the otocyst (between 9.5 dpc and 11.5 dpc embryos fading away after 12 dpc) and in the developing eye. Lower expression is found in different sites of the embryos such as developing brain, the lungs and the cardiac outflow tract.|||Heterodimer with NPLOC4, this heterodimer binds VCP and inhibits Golgi membrane fusion. Interacts with USP13 (By similarity). Interacts with ZFAND2B; probably through VCP (PubMed:24160817).|||Nucleus|||cytosol http://togogenome.org/gene/10090:Ubald2 ^@ http://purl.uniprot.org/uniprot/Q8BQH4 ^@ Similarity ^@ Belongs to the UBALD family. http://togogenome.org/gene/10090:Bri3 ^@ http://purl.uniprot.org/uniprot/E9PUB2|||http://purl.uniprot.org/uniprot/P28662|||http://purl.uniprot.org/uniprot/Q8C4X5|||http://purl.uniprot.org/uniprot/Q8C7X8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BRI3 family.|||High expression in cerebral cortex, and in cerebellar cortex.|||Interacts with BRI3BP. Interacts with MGAT1 and IFITM3 (By similarity).|||Lysosome membrane|||Membrane|||Participates in tumor necrosis factor-alpha (TNF)-induced cell death (Ref.4). May be a target of Wnt/beta-catenin signaling in the liver (By similarity).|||Up-regulated during TNF-mediated inflammation and immunity.|||perinuclear region http://togogenome.org/gene/10090:Ncor2 ^@ http://purl.uniprot.org/uniprot/E9PY55|||http://purl.uniprot.org/uniprot/E9Q9V3|||http://purl.uniprot.org/uniprot/F8VQL9|||http://purl.uniprot.org/uniprot/Q9WU42 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the N-CoR nuclear receptor corepressors family.|||Forms a large corepressor complex that contains SIN3A/B and histone deacetylases HDAC1 and HDAC2. This complex associates with the thyroid (TR) and the retinoid acid receptors (RAR) in the absence of ligand, and may stabilize their interaction with TFIIB. Interacts directly with RARA in the absence of ligand; the interaction represses RARA activity. Interacts (isoform SMRT) with HDAC10. Interacts with MINT. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with CBFA2T3 and ATXN1L. Interacts with RARB; the interaction is weak and does not repress RARB transactivational activity. Interacts with HDAC7 and C1D. Interacts with NR4A2; this interaction increases in the absence of PITX3. Interacts with BCL6 (via the BTB domain), required for BCL6 transcriptional repressor activity on a subset of target genes. Forms ternary complexes with BCOR and BCL6 on target gene promoters but, on enhancer elements, interacts with BCL6 and HDAC3 to repress proximal gene expression. May interact with DEAF1. Interacts with RXRA. Interacts with MECP2. Interacts with ZBTB7A (By similarity). Interacts with AR (By similarity). Interacts with TBL1Y (By similarity). Interacts with SANBR (via the BTB domain) (PubMed:33831416).|||Nucleus|||The N-terminal region contains repression functions that are divided into three independent repression domains (RD1, RD2 and RD3). The C-terminal region contains the nuclear receptor-interacting domains that are divided in two separate interaction domains (ID1 and ID2).|||The two interaction domains (ID) contain a conserved sequence referred to as the CORNR box. This motif is required and sufficient to permit binding to unligated TR and RARS. Sequences flanking the CORNR box determine nuclear hormone receptor specificity.|||Transcriptional corepressor. Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors. Involved in the regulation BCL6-dependent of the germinal center (GC) reactions, mainly through the control of the GC B-cells proliferation and survival. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation.|||Ubiquitous. Also widely expressed in early embryos. http://togogenome.org/gene/10090:Mtarc1 ^@ http://purl.uniprot.org/uniprot/Q9CW42 ^@ Cofactor|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Catalyzes the reduction of N-oxygenated molecules, acting as a counterpart of cytochrome P450 and flavin-containing monooxygenases in metabolic cycles. As a component of prodrug-converting system, reduces a multitude of N-hydroxylated prodrugs particularly amidoximes, leading to increased drug bioavailability. May be involved in mitochondrial N(omega)-hydroxy-L-arginine (NOHA) reduction, regulating endogenous nitric oxide levels and biosynthesis. Postulated to cleave the N-OH bond of N-hydroxylated substrates in concert with electron transfer from NADH to cytochrome b5 reductase then to cytochrome b5, the ultimate electron donor that primes the active site for substrate reduction.|||Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase and MTARC1.|||Comprises two structural domains, the molybdenum cofactor/Moco sulfurase C-terminal (MOSC) domain and the MOSC N-terminal region, forming a cleft that accommodates Moco. The MOSC domain, which contains a large seven-stranded mostly antiparallel beta-barrel, engages multiple interactions with Moco both pterin ring and phosphate group, allowing for a tight coordination of Moco within the core of the enzyme.|||Membrane|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Eno1 ^@ http://purl.uniprot.org/uniprot/P17182|||http://purl.uniprot.org/uniprot/Q5FW97 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the enolase family.|||Binds two Mg(2+) per subunit. Required for catalysis and for stabilizing the dimer.|||Cell membrane|||Cytoplasm|||During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells, and to the alpha/gamma heterodimer in nerve cells. In embryonic muscle, ENO1 is highly expressed until 17 dpc. Decreased levels from P5.|||Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses. May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons. Stimulates immunoglobulin production.|||ISGylated.|||Lysine 2-hydroxyisobutyrylation (Khib) by p300/EP300 activates the phosphopyruvate hydratase activity.|||Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific. ENO1 interacts with PLG in the neuronal plasma membrane and promotes its activation. The C-terminal lysine is required for this binding (By similarity). In vitro, interacts with several glycolytic enzymes including PKM, PGM, CKM and aldolase (PubMed:9169614). Also binds troponin, in vitro (PubMed:9169614). Interacts with ENO4 and PGAM2 (PubMed:23446454). Interacts with CMTM6 (By similarity).|||Testis. Found in the principal piece of sperm tail (at protein level). The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons. In striated muscle, expression of ENO1 appears to be independent of fiber type. http://togogenome.org/gene/10090:Nif3l1 ^@ http://purl.uniprot.org/uniprot/Q9EQ80 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GTP cyclohydrolase I type 2/NIF3 family.|||Cytoplasm|||Expressed in the developing brain from 10.5 dpc until 14.5 dpc. The expression decreases after 16.5 dpc, but an up-regulation is observed at P5 and the expression remains constant thereafter.|||Homodimer (By similarity). Interacts with COPS2 (PubMed:12522100). Interacts with THOC7 (PubMed:12951069).|||May function as a transcriptional corepressor through its interaction with COPS2, negatively regulating the expression of genes involved in neuronal differentiation.|||Nucleus|||Ubiquitous. Detected in all tissues tested with higher expression in cerebellum, heart and kidney and to a lower level in cerebrum, lung, liver, spleen and muscle. http://togogenome.org/gene/10090:Spata3 ^@ http://purl.uniprot.org/uniprot/Q9D9T6 ^@ Miscellaneous|||Tissue Specificity ^@ May be due to competing acceptor splice site and by intron retention.|||May be due to competing acceptor splice site.|||May be due to competing donor splice site.|||Strongly expressed in testis. Faintly expressed in epididymis, ovary, spleen, kidney, lung, heart, brain, epididymis, liver and skeletal muscle. http://togogenome.org/gene/10090:Or7c70 ^@ http://purl.uniprot.org/uniprot/Q7TQU8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fer ^@ http://purl.uniprot.org/uniprot/P70451|||http://purl.uniprot.org/uniprot/Q3TZJ5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphatidic acid binding (By similarity). Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS).|||Autophosphorylated.|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.|||Cell junction|||Cell membrane|||Cell projection|||Cytoplasm|||Detected in liver and testis. Isoform 4 is detected only in testis (at protein level). Widely expressed.|||Homotrimer. Isoform 4 is a monomer, due to the absence of the N-terminal coiled coil domains. Interacts with CTNND1, EGFR, FLT3, PECAM1 and PDGFR. Interacts (via SH2 domain) with CTTN. Component of a complex that contains at least FER, CTTN and PTK2/FAK1 (By similarity). Interacts with IRS1 and PIK3R1. Interacts with STAT3. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320'. Interacts with JAK1. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Interacts with ARHGDIA, NRP1, PLEC and TMF1.|||Membrane|||No visible phenotype, and the mice are fertile. Mice have reduced CTTN phosphorylation. Mice lacking both Fps/Fes and Fer activity are viable and fertile, but produce slightly fewer pups per litter than normal. They display elevated levels of circulating neutrophils, erythrocytes and platelets, while other cell counts are normal.|||Nucleus|||Polyubiquitinated; this leads to proteasomal degradation.|||The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.|||The coiled coil domains mediate homooligomerization and are required for location at microtubules.|||Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3 according to PubMed:10878010 and PubMed:19159681, but clearly plays a redundant role in STAT3 phosphorylation. According to PubMed:11134346, cells where wild type FER has been replaced by a kinase-dead mutant show no reduction in STAT3 phosphorylation. Phosphorylates TMF1. Isoform 3 lacks kinase activity.|||Up-regulated by insulin in myogenic cells (in vitro).|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Ms4a15 ^@ http://purl.uniprot.org/uniprot/Q3UPL6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MS4A family.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Galnt2 ^@ http://purl.uniprot.org/uniprot/Q6PB93 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region (By similarity). Involved in O-linked glycosylation of APOC-III, ANGPTL3 and PLTP. It participates in the regulation of HDL-C metabolism (PubMed:27508872).|||GALNT2 knockout results in significant embryonic lethality. Surviving mice show decreased body weight, abnormal craniofacial features, and neuro-behavioral abnormalities, including deficits in coordination and impaired responses to acoustic stimuli (PubMed:32293671). Knockout mice have reduced HDL-C levels compared to wild-type littermate (PubMed:27508872).|||Golgi stack membrane|||Secreted|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.|||Widely expressed at high level. http://togogenome.org/gene/10090:Ranbp9 ^@ http://purl.uniprot.org/uniprot/E9Q5D6|||http://purl.uniprot.org/uniprot/P69566 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RANBP9/10 family.|||Cell membrane|||Cytoplasm|||May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways. Acts as a mediator of cell spreading and actin cytoskeleton rearrangement. Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA.|||Nucleus|||Part of a complex consisting of RANBP9, MKLN1 and GID8. Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with GTP-bound Ran, AR, CDC2L1/p110C, CALB1, S100A7, USP11, SOS1 or SOS2, GID8, and FMR1. Interacts with the Dyrk kinases HIPK2, DYRK1A, and DYRK1B. Interacts with TP73 isoform Alpha but not with TP53. Interacts with the HGF receptor MET and the integrins ITGB1 and ITGB2, but not with ITGAL. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Directly interacts with RANBP10. Interacts with YPEL5 (By similarity). Interacts with MKLN1 (PubMed:18710924). Interacts with DDX4 (PubMed:14648869). Interacts with NGFR (PubMed:12963025). Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886).|||Phosphorylated in response to stress.|||The SPRY domain mediates the interaction with MET, AR, and CDC2L1.|||Ubiquitinated. Polyubiquitination targets the protein for rapid degradation via the ubiquitin system (By similarity).|||Ubiquitously expressed, with highest levels in maturating spermatocytes. http://togogenome.org/gene/10090:Cyp4f39 ^@ http://purl.uniprot.org/uniprot/Q8BGU0 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Kirrel3 ^@ http://purl.uniprot.org/uniprot/Q8BR86 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At embryonic day 11.5, it is expressed in the differentiating zones of various regions, such as the caudate-putamen, the geniculate body, the thalamus, the amygdala and the brainstem. This expression persists in the adult, although expression is lower. After birth, highly expressed in the glomerular and mitral layers of the olfactory bulb, the cortical plate of the neocortex, the cochlear nucleus, and the molecular and granule cell layers of the cerebellum. In the hippocampus, expression is first observed in the dentate gyrus at postnatal day 7.|||Belongs to the immunoglobulin superfamily.|||Cell membrane|||Expressed mainly in adult brain, bone marrow and stromal cells (PubMed:12665856). Expressed in diverse regions of the brain, including the cortex, hippocampus, striatum, olfactory bulb and cerebellum (PubMed:15908127, PubMed:26283919). In brain, expressed in pontine nucleus neurons (at protein level) (PubMed:21241806). In hippocampus, produced in both the dentate granule neurons and the GABAergic neurons, but not the CA3 neurons (PubMed:26575286). Expressed in subpopulations of vomeronasal sensory neurons (PubMed:23637329). Expressed in a subset of neurons in dorsal root ganglia (PubMed:18752272).|||Homodimer; mediates homophilic interactions to promote cell adhesion (PubMed:26575286). Interacts with NPHS1; forms heterodimers with NPHS1 (PubMed:15843475, PubMed:18752272). Interacts with NPHS2/podocin (via the C-terminus) (By similarity). Interacts with CASK. Interacts (via extracellular region) with MAP1B. Interacts (via extracellular region) with MYO16. Interacts (via intracellular region) with ATP1B1. Interacts (via intracellular region) with SHMT2. Interacts (via intracellular region) with UFC1 (By similarity).|||Mice are viable and their size is normal. Mice show defects of the accessory olfactory system characterized by disorganization of the glomerular layer of the posterior accessory olfactory bulb and formation of fewer, larger glomeruli. Mice display a loss of male-male aggression in a resident-intruder assay (PubMed:23637329). Mice display moderate hyperactivity in a familiar, but not novel, environment and defective novel object recognition with normal performances in Morris water maze spatial learning and memory, contextual fear conditioning and extinction, and pattern separation tests (PubMed:26283919). Young mutant mice form fewer synapse-forming structures between dentate granule neurons and GABAergic neurons than normal mice, while the synapses that connect dentate granule neurons to CA3 neurons form normally. This may affect the balance of activity across the two types of dentate granule synapses and the CA3 neurons, leading to hyperactivity (PubMed:26575286).|||Secreted|||Synaptic adhesion molecule required for the formation of target-specific synapses (PubMed:23637329, PubMed:26575286). Required for formation of target-specific synapses at hippocampal mossy fiber synapses. Required for formation of mossy fiber filopodia, the synaptic structures connecting dentate granule and GABA neurons. Probably acts as a homophilic adhesion molecule that promotes trans-cellular interactions and stabilize mossy fiber filipodia contact and subsequent synapse formation (PubMed:26575286). Required for the coalescence of vomeronasal sensory neuron axons (PubMed:23637329). May be involved in the hematopoietic supportive capacity of stroma cells; the secreted extracellular domain is directly responsible for supporting hematopoietic stem cells (PubMed:12665856).|||Undergoes proteolysis by a metalloprotease and gives rise to a soluble form.|||axon|||dendrite http://togogenome.org/gene/10090:Wwc1 ^@ http://purl.uniprot.org/uniprot/Q5SXA9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WWC family. KIBRA subfamily.|||Cytoplasm|||Deficient mice have significant deficits in hippocampal long-term potentiation (LTP) and long-term depression (LTD)vcand have profound learning and memory defects.|||Expressed in mammary tissue throughout development (at protein level). Strongly up-regulated during pregnancy, falls during lactation and is again up-regulated during involution of the gland at weaning.|||Homodimer. Interacts with DDN. Interacts with DYNLL1 and histone H3. The interaction with DYNLL1 is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin and the interaction with histone H3 ensures proper regulatory interaction of WWC1-DYNLL1-ESR1 complexes with target chromatin. Interacts (via WW domains) with DDR1 (via PPxY motif) in a collagen-regulated manner. Interacts with PRKCZ (via the protein kinase domain). Forms a tripartite complex with DDR1 and PRKCZ, but predominantly in the absence of collagen. Interacts (via the ADDV motif) with PATJ (via PDZ domain 8). Interacts (via WW domains) with SYNPO (via PPxY motifs). Interacts with NF2 and SNX4 (By similarity). Interacts with CCDC141; retains AMPAR in the cytosol after internalization (PubMed:31730661).|||Mammary epithelium.|||Nucleus|||Phosphorylation at Ser-542 and Ser-923 by CDK1 in response to spindle damage stress regulates mitotic exit, these two sites are dephosphorylated by CDC14B.|||Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ and may be associated with memory performance (By similarity). Regulates collagen-stimulated activation of the ERK/MAPK cascade. Plays an important role in regulating AMPA-selective glutamate receptors (AMPARs) trafficking (PubMed:31730661).|||The C2-domain mediates homodimerization.|||perinuclear region|||ruffle membrane http://togogenome.org/gene/10090:Pik3r5 ^@ http://purl.uniprot.org/uniprot/Q5SW28 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Greatly activated by G gamma proteins.|||Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit. Interacts with beta-gamma G protein dimers (By similarity).|||Nucleus|||Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity).|||The heterodimerization region allows the binding to the catalytic subunit. http://togogenome.org/gene/10090:Rell2 ^@ http://purl.uniprot.org/uniprot/Q8BRJ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RELT family.|||Cell membrane|||Induces activation of MAPK14/p38 cascade, when overexpressed. Induces apoptosis, when overexpressed.|||Interacts with RELT, RELL1, OXSR1, PLSCR1 and TRAF2. http://togogenome.org/gene/10090:Tdg ^@ http://purl.uniprot.org/uniprot/P56581 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the uracil-DNA glycosylase (UDG) superfamily. TDG/mug family.|||DNA glycosylase that plays a key role in active DNA demethylation: specifically recognizes and binds 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in the context of CpG sites and mediates their excision through base-excision repair (BER) to install an unmethylated cytosine (PubMed:21817016). Cannot remove 5-hydroxymethylcytosine (5hmC). According to an alternative model, involved in DNA demethylation by mediating DNA glycolase activity toward 5-hydroxymethyluracil (5hmU) produced by deamination of 5hmC (PubMed:21722948). Also involved in DNA repair by acting as a thymine-DNA glycosylase that mediates correction of G/T mispairs to G/C pairs: in the DNA of higher eukaryotes, hydrolytic deamination of 5-methylcytosine to thymine leads to the formation of G/T mismatches. Its role in the repair of canonical base damage is however minor compared to its role in DNA demethylation. It is capable of hydrolyzing the carbon-nitrogen bond between the sugar-phosphate backbone of the DNA and a mispaired thymine. In addition to the G/T, it can remove thymine also from C/T and T/T mispairs in the order G/T >> C/T > T/T. It has no detectable activity on apyrimidinic sites and does not catalyze the removal of thymine from A/T pairs or from single-stranded DNA. It can also remove uracil and 5-bromouracil from mispairs with guanine.|||Embryonic lethality between 10.5 and 12.5 dpc. Embryos display specific patterning defects of the developing heart; vasculogenesis defects of dorsal aortae, carotid arteries and branchial arteries. Global defects of angiogenesis are also observed. Defects are due to epigenetic aberrations affecting the expression of developmental genes, coincident with imbalanced histone modification and CpG methylation at promoters of affected genes.|||Homodimer. Interacts with AICDA and GADD45A (By similarity).|||Nucleus|||Sumoylation on Lys-341 by either SUMO1 or SUMO2 induces dissociation of the product DNA. http://togogenome.org/gene/10090:Or51a6 ^@ http://purl.uniprot.org/uniprot/Q8VH16 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrba ^@ http://purl.uniprot.org/uniprot/Q9ESE1 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By lipopolysaccharide (LPS).|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with TOM1 and TOLLIP.|||Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (PubMed:11254716). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (By similarity).|||Isoform 1 is expressed in the brain, is absent from the lung and the bone marrow and is less abundant in the spleen. Isoform 2 is expressed in the spleen, lung, brain and bone marrow. Isoform 3 is expressed in the brain, is absent from the bone marrow and is less abundant in the spleen and lung.|||Lysosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Wdr5 ^@ http://purl.uniprot.org/uniprot/P61965 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat WDR5/wds family.|||Contributes to histone modification (By similarity). May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4' (By similarity). As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3 (By similarity). H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (By similarity). May regulate osteoblasts differentiation (PubMed:11551928). In association with RBBP5 and ASH2L, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (By similarity).|||Expressed in liver (at protein level). Detected in brain, testis and kidney.|||Interacts with PAXBP1; the interaction is direct and links a WDR5-containing histone methyltransferase complex to PAX7 and PAX3 (PubMed:22862948). Interacts with HCFC1 (By similarity). Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (By similarity). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 (By similarity). Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7 (PubMed:21335234). Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin (PubMed:21335234). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (By similarity). Interacts with KMT2A/MLL1 (via WIN motif) and RBBP5; the interaction is direct (By similarity). Component ofthe ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity). In the complex, it probably interacts directly with KAT2A, MBIP and KAT14 (By similarity). Interacts with histone H3 (By similarity). Interacts with SETD1A (via WIN motif) (By similarity). Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for 'Lys-4' of histone H3 (By similarity). Interacts with ZNF335 (PubMed:23178126). Components of this complex may associate with components of the ZNF335-CCAR2-EMSY nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (By similarity). Interacts with PER1 (By similarity). Interacts with KMT2D (via WIN motif) (PubMed:21335234). Interacts with KMT2B (via WIN motif), KMT2C (via WIN motif) and SETD1B (via WIN motif) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Calcrl ^@ http://purl.uniprot.org/uniprot/A2AR99|||http://purl.uniprot.org/uniprot/Q9R1W5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Expressed predominantly in the lung, thymus, heart and brain.|||Heterodimer of CALCRL and RAMP1, RAMP2 or RAMP3.|||Heterodimer of CALCRL and RAMP3 (By similarity). Heterodimer of CALCRL and RAMP1 or CALCRL and RAMP2 (By similarity).|||Membrane|||Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP2 or RAMP3. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity).|||Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP2 or RAMP3. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. http://togogenome.org/gene/10090:Tbrg4 ^@ http://purl.uniprot.org/uniprot/Q91YM4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAST kinase family.|||Expression detected in spleen, testis, colon, heart, smooth muscle, kidney, brain, lung, liver, brown and white adipose tissue with highest expression in testis, heart, smooth muscle and brown adipose tissue.|||Mitochondrion matrix|||Plays a role in processing of mitochondrial RNA precursors and in stabilization of a subset of mature mitochondrial RNA species, such as MT-CO1, MT-CO2, MT-CYB, MT-CO3, MT-ND3, MT-ND5 and MT-ATP8/6. May play a role in cell cycle progression. http://togogenome.org/gene/10090:Gm21247 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Stambpl1 ^@ http://purl.uniprot.org/uniprot/Q76N33 ^@ Cofactor|||Domain|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the peptidase M67C family.|||Binds 2 Zn(2+) ions per subunit.|||The JAMM motif is essential for the protease activity.|||Ubiquitously expressed. Isoform 1 is widely expressed while isoform 2 is testis-specific.|||Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Acts as a positive regulator of the TORC1 signaling pathway by mediating 'Lys-63'-linked deubiquitination of SESN2, thereby inhibiting SESN2-interaction with the GATOR2 complex. Does not cleave 'Lys-48'-linked polyubiquitin chains. http://togogenome.org/gene/10090:Vil1 ^@ http://purl.uniprot.org/uniprot/Q62468|||http://purl.uniprot.org/uniprot/Q8CEJ4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the villin/gelsolin family.|||Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity. Two major calcium-sensitive sites are involved in conformational changes and determine separate functional properties: the first site (Glu-25, Asp-44 and Glu-74) regulates the actin-capping and actin-severing activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates only the actin-severing activity (By similarity).|||Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination.|||Expressed in small intestin, colon, kidney and enterocytes (at protein level).|||Mice are viable and fertile. The ultrastructure of the intestinal brush border is normal. Show increase epithelial cell apoptosis and are more sensitive to extran sodium sulfate-induced colitis. Newborn mice inoculated with S.flexneri are not susceptible to infection; cell invasion and intestinal inflammation were not observed, even though bacteria were seen in large number in the intestinal lumen, close to the intestinal epithelial cells (IEC) brush border.|||Monomer. Homodimer; homodimerization is necessary for actin-bundling. Associates with F-actin; phosphorylation at tyrosine residues decreases the association with F-actin. Interacts (phosphorylated at C-terminus tyrosine phosphorylation sites) with PLCG1 (via the SH2 domains) (By similarity). Interacts (phosphorylated form) with PLCG1; the interaction is enhanced by hepatocyte growth factor (HGF).|||Phosphorylated on tyrosine residues by SRC. The unphosphorylated form increases the initial rate of actin-nucleating activity, whereas the tyrosine phosphorylated form inhibits actin-nucleating activity, enhances actin-bundling activity and enhances actin-severing activity by reducing high Ca(2+) requirements. The tyrosine phosphorylated form does not regulate actin-capping activity. Tyrosine phosphorylation is essential for cell migration: tyrosine phosphorylation sites in the N-terminus half regulate actin reorganization and cell morphology, whereas tyrosine phosphorylation sites in the C-terminus half regulate cell migration via interaction with PLCG1 (By similarity). Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration.|||cytoskeleton|||filopodium|||filopodium tip|||lamellipodium|||microvillus|||ruffle http://togogenome.org/gene/10090:Stx2 ^@ http://purl.uniprot.org/uniprot/Q3TJ55|||http://purl.uniprot.org/uniprot/Q80W45 ^@ Similarity ^@ Belongs to the syntaxin family. http://togogenome.org/gene/10090:Cdh11 ^@ http://purl.uniprot.org/uniprot/P55288|||http://purl.uniprot.org/uniprot/Q8C7Q6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cadherins are calcium-dependent cell adhesion proteins.|||Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Required for proper focal adhesion assembly. Involved in the regulation of cell migration.|||Cell membrane|||In the testis, expression is highest in fetal gonad and decreases 8-fold in newborn.|||Interacts with PCDH8.|||Membrane|||Selectively expressed in osteoblastic cell lines, precursor cell lines of osteoblasts, and primary osteoblastic cells from calvaria, as well as in lung, testis, and brain tissues at low levels.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Tmem248 ^@ http://purl.uniprot.org/uniprot/Q3TBN1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM248 family.|||Membrane http://togogenome.org/gene/10090:Nrros ^@ http://purl.uniprot.org/uniprot/Q8BMT4 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRC32/LRRC33 family.|||Cell membrane|||Down-regulated by IFN-gamma (IFNG), LPS or TNF-alpha in bone marrow-derived macrophages (BMDMs).|||Endoplasmic reticulum membrane|||Interacts with TGFB1; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1 (PubMed:29909984). Interacts (via LRR repeats) with TLR2, TLR3, TLR4, TLR9 and probably other Toll-like receptors (By similarity). Interacts with CYBB/NOX2; the interaction is direct (PubMed:24739962).|||Key regulator of transforming growth factor beta-1 (TGFB1) specifically required for microglia function in the nervous system (PubMed:29909984). Required for activation of latent TGF-beta-1 in macrophages and microglia: associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGFB1, and regulates integrin-dependent activation of TGF-beta-1 (PubMed:29909984). TGF-beta-1 activation mediated by LRRC33/NRROS is highly localized: there is little spreading of TGF-beta-1 activated from one microglial cell to neighboring microglia, suggesting the existence of localized and selective activation of TGF-beta-1 by LRRC33/NRROS (PubMed:29909984). Indirectly plays a role in Toll-like receptor (TLR) signaling: ability to inhibit TLR-mediated NF-kappa-B activation and cytokine production is probably a consequence of its role in TGF-beta-1 signaling (Probable).|||Mainly expressed in cells of hematopoietic origin, such as in immune organs such as lymph nodes, thymus and spleen (PubMed:24739962, PubMed:29909984). Among leukocytes, expressed at higher level in myeloid cell such as macrophages, neutrophils and dendritic cells (PubMed:24739962). Highly expressed in central nervous system-resident macrophages, including microglia and perivascular macrophages (PubMed:28459434, PubMed:29909984).|||Mice develop paraparesis and neurodegeneration and display reactive microglia caused by defects in TGF-beta-1 signaling (PubMed:29909984). Mice are viable at six-weeks of age and immune organs and leukocyte subsets are not affected (PubMed:24739962). However, significantly increased reactive oxygen species (ROS) production is observed in primary bone marrow-derived macrophages (BMDMs) upon zymosan stimulation (PubMed:24739962). Mice are more susceptible to Toll-like receptor (TLR) ligand challenges: the macrophages and dendritic cells produce more pro-inflammatory cytokines through increased activation of MAPK and NF-kappa-B (PubMed:24550525). By two months of age, mice begin to display neurological symptoms including defects in motor control and strength and die before six months of age (PubMed:28459434, PubMed:29909984). Mice show microglial development defects (PubMed:28459434, PubMed:29909984). Mice develop progressive paraparesis associated with loss of myelin and axons in the spinal cord and brainstem (PubMed:29909984).|||N-glycosylated.|||Was initially thought to act as a negative regulator of reactive oxygen species (ROS) that limits ROS production by phagocytes during inflammatory response, thereby playing a role during host defense (PubMed:24739962). However, these results were based on indirect evidences and could not be confirmed by another group (PubMed:29909984). It was later shown to act as a key regulator of transforming growth factor beta-1 (TGFB1) (PubMed:29909984). http://togogenome.org/gene/10090:Ptk6 ^@ http://purl.uniprot.org/uniprot/Q05AA8|||http://purl.uniprot.org/uniprot/Q64434 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by EGF, NRG1 and IGF1. Inhibited by SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region. Interaction between Trp-184 within SH2-TK linker region and the catalytic domain appears essential for positive regulation of kinase activity.|||Autophosphorylated. Autophosphorylation of Tyr-342 leads to an increase of kinase activity. Tyr-447 binds to the SH2 domain when phosphorylated and negatively regulates kinase activity (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. BRK/PTK6/SIK subfamily.|||Cytoplasm|||Deficient mice have an increased cell turnover in the small intestine, which is accompanied by increased villus length and crypt depth and delayed enterocyte differentiation that is accompanied by increased PTK/AKT and WNT signaling.|||Expressed only in epithelial tissues, including the skin and lining of the alimentary canal. Restricted to the cell layers immediately above the proliferative cell zone in these epithelia.|||First detected at day 15.5 of gestation in the embryo, where it is expressed in the newly forming granular layer of the skin. Is found in stomach at day 17.5.|||Interacts with KHDRBS1. Interacts with phosphorylated IRS4 (By similarity). Interacts with GAP-A.p65. Interacts with ADAM15 (By similarity). Interacts (via SH3 and SH2 domains) with phosphorylated IRS4 (By similarity). Interacts (via SH3 domain) with SFPQ (By similarity). Interacts with EGFR and ERBB2 (By similarity). Interacts with STAP2 (By similarity). Interacts with PNX (By similarity). Interacts with SFPQ (By similarity). Interacts with PTK/ATK (By similarity). Interacts with CTNNB1 (By similarity).|||Membrane|||Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.|||Nucleus|||The SH3 domain plays a major role in substrate interactions. The SH2 domain of PTK6 plays a role in protein-protein interactions, but is likely more important for the regulation of catalytic activity (By similarity).|||ruffle http://togogenome.org/gene/10090:Xbp1 ^@ http://purl.uniprot.org/uniprot/O35426 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by EP300; acetylation positively regulates the transcriptional activity of XBP1 isoform 2 (PubMed:20955178). Isoform 2 is deacetylated by SIRT1; deacetylation negatively regulates the transcriptional activity of XBP1 isoform 2 (PubMed:20955178).|||Belongs to the bZIP family.|||Cytoplasm|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Expressed mainly in exocrine glands and bone precursors in the embryonic mouse (PubMed:7693055).|||Functions as a stress-inducible potent transcriptional activator during endoplasmic reticulum (ER) stress by inducing unfolded protein response (UPR) target genes via binding to the UPR element (UPRE). Up-regulates target genes encoding ER chaperones and ER-associated degradation (ERAD) components to enhance the capacity of productive folding and degradation mechanism, respectively, in order to maintain the homeostasis of the ER under ER stress (PubMed:11850408, PubMed:14559994). Plays a role in the production of immunoglobulins and interleukin-6 in the presence of stimuli required for plasma cell differentiation, and promotes as well membrane phospholipid biosynthesis necessary for ER expansion (PubMed:12612580, PubMed:17213183). Contributes to the VEGF-induced endothelial cell (EC) growth and proliferation in a Akt/GSK-dependent and/or -independent signaling pathway, respectively, leading to beta-catenin nuclear translocation and E2F2 gene expression. Promotes umbilical vein EC apoptosis and atherosclerotisis development in a caspase-dependent signaling pathway, and contributes to VEGF-induced EC proliferation and angiogenesis in adult tissues under ischemic conditions. Involved in the regulation of endostatin-induced autophagy in EC through BECN1 transcriptional activation. Plays a role as an oncogene by promoting tumor progression: stimulates zinc finger protein SNAI1 transcription to induce epithelial-to-mesenchymal (EMT) transition, cell migration and invasion of breast cancer cells (By similarity). Involved in adipocyte differentiation by regulating lipogenic gene expression during lactation (PubMed:23623498, PubMed:25223794). Plays a role in the survival of both dopaminergic neurons of the substantia nigra pars compacta (SNpc), by maintaining protein homeostasis and of myeloma cells (PubMed:12902539, PubMed:24753614). Increases insulin sensitivity in the liver as a response to a high carbohydrate diet, resulting in improved glucose tolerance (PubMed:20348926). Improves also glucose homeostasis in an ER stress- and/or insulin-independent manner through both binding and proteasome-induced degradation of the transcription factor FOXO1, hence resulting in suppression of gluconeogenic genes expression and in a reduction of blood glucose levels (PubMed:21317886). Controls the induction of de novo fatty acid synthesis in hepatocytes by regulating the expression of a subset of lipogenic genes in an ER stress- and UPR-independent manner (PubMed:18556558). Binds to the 5'-CCACG-3' motif in the PPARG promoter (PubMed:25223794). Associates preferentially to the HDAC3 gene promoter region in a disturbed flow-dependent manner. Binds to the BECN1 gene promoter region. Binds to the CDH5/VE-cadherin gene promoter region. Binds to the ER stress response element (ERSE) upon ER stress (By similarity).|||Functions as a transcription factor during endoplasmic reticulum stress by regulating the unfolded protein response (UPR). Required for cardiac myogenesis and hepatogenesis during embryonic development and the development of secretory tissues such as exocrine pancreas and salivary gland (PubMed:10425189, PubMed:10652269, PubMed:16362047, PubMed:17612490). Involved in differentiation of B lymphocytes to plasma cells and production of immunoglobulins. Modulates the cellular response to ER stress in a PIK3R-dependent manner. Binds to the cis-acting X box present in the promoter regions of major histocompatibility complex class II genes (By similarity). Involved in VEGF-induced endothelial cell (EC) proliferation and retinal blood vessel formation during embryonic development but also for angiogenesis in adult tissues under ischemic conditions (PubMed:23529610). Functions also as a major regulator of the UPR in obesity-induced insulin resistance and type 2 diabetes for the management of obesity and diabetes prevention (PubMed:15486293).|||Isoform 1 and isoform 2 are expressed at higher level in branch curves of vessel walls and in atherosclerotic plaques relative to healthy segments of the same aortas (at protein level) (PubMed:19416856). Expressed in skeletal muscles, plasma cells and pancreatic beta cells (PubMed:17612490). Isoform 1 and isoform 2 are expressed in gonadal adipose tissue. Isoform 1 is expressed in inguinal adipose tissue (PubMed:23623498).|||Isoform 1 interacts with HM13. Isoform 1 interacts with RNF139; the interaction induces ubiquitination and degradation of isoform 1. Isoform 1 interacts (via luminal domain) with DERL1; the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage. Isoform 1 interacts with isoform 2; the interaction sequesters isoform 2 from the nucleus and enhances isoform 2 degradation in the cytoplasm. Isoform 1 interacts with HDAC3 and AKT1; the interactions occur in endothelial cell (EC) under disturbed flow. Isoform 1 interacts with the oncoprotein FOS. Isoform 2 interacts with ATF6; the interaction occurs in a ER stress-dependent manner and is required for DNA binding to the unfolded protein response element (UPRE). Isoform 2 interacts with PIK3R1; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus and the unfolded protein response (UPR) XBP1-dependent target genes activation in a ER stress- and/or insulin-dependent but PI3K-independent manner (By similarity). Isoform 2 interacts with SIRT1 (PubMed:20955178). Isoform 2 interacts with PIK3R1 and PIK3R2; the interactions are direct and induce translocation of XBP1 isoform 2 into the nucleus and the unfolded protein response (UPR) XBP1-dependent target genes activation in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348926). Isoform 2 interacts with FOXO1; the interaction is direct and leads to FOXO1 ubiquitination and degradation via the proteasome pathway in hepatocytes (PubMed:21317886).|||Isoform 1 transmembrane signal-anchor domain is necessary for its own mRNA to be recruited to the endoplasmic reticulum (ER) which will undergo unconventional ERN1-dependent splicing in response to ER stress. Isoform 1 N-terminus and C-terminus regions are necessary for DNA-binding and weak transcriptional activity, respectively. Isoform 2 N-terminus and C-terminus regions are necessary for DNA-binding and strong transcriptional activity upon ER stress, respectively. Isoform 2 C-terminus region contains a nuclear exclusion signal (NES) at positions 182 through 204. Isoform 2 C-terminus region contains a degradation domain at positions 204 through 256 (By similarity). Isoform 1 and isoform 2 N-terminus domains are necessary for nuclear localization targeting. Isoform 1 C-terminus domain confers localization to the cytoplasm and is sufficient to impose rapid degradation (PubMed:16332684).|||Isoform 2 is up-regulated during adipocyte differentiation (PubMed:25223794). Isoform 2 is up-regulated upon refeeding after a fasting period in liver and in ob/ob mice (obese) (at protein level) (PubMed:20348926). Induced by chemical activators of the unfolded protein response (UPR) such as tunicamycin, DTT and thapsigargin (PubMed:17612490). Up-regulated after partial hepatectomy during the acute phase response (PubMed:10652269). Isoform 1 and isoform 2 are up-regulated by interleukin-4 in B cells in a STAT6-dependent manner (PubMed:12612580). Isoform 1 and isoform 2 are up-regulated during lactation and by the lactogenic hormone prolactin (PubMed:23623498). Isoform 2 is up-regulated by prolonged feeding of high-carbohydrate diets in hepatocytes in absence of ER-stress (PubMed:18556558). Isoform 2 is up-regulated by insulin-like growth factor and glucose starvation (PubMed:17612490). Isoform 2 is up-regulated during plasma-cell differentiation in response to endoplasmic reticulum (ER) stress, such as lipopolysaccharide (LPS) (PubMed:11780124, PubMed:11850408, PubMed:12612580).|||Membrane|||Mice embryos die at 12.5-13.5 dpc and display less blood vessels (PubMed:23529610). Embryos display hypoplastic livers, cellular necrosis in the myocardium, hypoplasia of the heart and die in utero from severe anemia (PubMed:10425189, PubMed:10652269). Mice display severe abnormalities in the development and function of secretory cells, such as plasma B cells and pancreatic acinar cells (PubMed:16362047). Haploinsufficient mice fed a high-fat diet gain more weight, display enhanced ER stress in adipose tissue, reduced insulin receptor signaling and develop peripheral insulin resistance and type 2 diabetes (PubMed:15486293). Endothelial-specific knockout mice show delayed retinal vascular development and impaired postischemic angiogenesis (PubMed:23529610, PubMed:23184933). Dopaminergic neuron-specific knockout mice display ER dysfonction and accumulation of abnormal protein aggregates (PubMed:24753614). Liver-specific knockout mice leads to reduced lipogenic gene expression and diminished hepatic lipid synthesis (PubMed:18556558). Adipocyte-specific knockout female mice fed with a regular or high-fat diet, show no alteration in body weight, adipose tissue mass, blood glucose, serum insulin and lipid levels; however during lactation adipose tissue mass increases and milk production decreases but mammary gland structure and milk composition remains normal (PubMed:23623498). Intestinal epithelial cell-specific knockout mice born and developed normally but displayed small intestinal mucosal inflammation in association with increased ER stress, a diminution of Paneth and goblet cells with reduced secretory granules (PubMed:18775308).|||Nucleus|||Plays a role in the unconventional cytoplasmic splicing processing of its own mRNA triggered by the endoplasmic reticulum (ER) transmembrane endoribonuclease ERN1: upon ER stress, the emerging XBP1 polypeptide chain, as part of a mRNA-ribosome-nascent chain (R-RNC) complex, cotranslationally recruits its own unprocessed mRNA through transient docking to the ER membrane and translational pausing, therefore facilitating efficient IRE1-mediated XBP1 mRNA isoform 2 production. In endothelial cells (EC), associated with KDR, promotes IRE1-mediated XBP1 mRNA isoform 2 production in a vascular endothelial growth factor (VEGF)-dependent manner, leading to EC proliferation and angiogenesis (By similarity). Functions as a negative feed-back regulator of the potent transcription factor XBP1 isoform 2 protein levels through proteasome-mediated degradation, thus preventing the constitutive activation of the ER stress response signaling pathway (PubMed:16332684). Inhibits the transactivation activity of XBP1 isoform 2 in myeloma cells (PubMed:12902539). Acts as a weak transcriptional factor. Together with HDAC3, contributes to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to EC survival under disturbed flow/oxidative stress. Binds to the ER stress response element (ERSE) upon ER stress. Binds to the consensus 5'-GATGACGTG[TG]N(3)[AT]T-3' sequence related to cAMP responsive element (CRE)-like sequences. Binds the Tax-responsive element (TRE) present in the long terminal repeat (LTR) of T-cell leukemia virus type 1 (HTLV-I) and to the TPA response elements (TRE). Associates preferentially to the HDAC3 gene promoter region in a static flow-dependent manner. Binds to the CDH5/VE-cadherin gene promoter region (By similarity).|||Potent transcriptional activator. Induced by unconventional ERN1-dependent splicing in response to endoplasmic reticulum stress. ERN1 cleaves a 26-bp fragment causing a frameshift of the mRNA transcript (PubMed:11780124, PubMed:11850408).|||Ubiquitinated, leading to proteasomal degradation in response to ER stress (PubMed:11780124, PubMed:12902539, PubMed:16332684).|||X-box-binding protein 1, cytoplasmic form and luminal form are produced by intramembrane proteolytic cleavage of ER membrane-anchored isoform 1 triggered by HM13/SPP in a DERL1-RNF139-dependent and VCP/p97-independent manner. X-box-binding protein 1, luminal form is ubiquitinated leading to proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Eps15 ^@ http://purl.uniprot.org/uniprot/P42567 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasm|||Early endosome membrane|||Interacts with HGS; the interaction bridges the interaction of STAM or STAM2 with EPS15. Isoform 2 interacts with HGS and AP2A2. Part of a complex at least composed of EPS15, HGS, and either STAM or STAM2. Binds AP2A2. Interacts with AP2B1; clathrin competes with EPS15. Binds STON2. Interacts (via its SH3-binding sites) with CRK. Interacts with SH3BP4/TTP. Interacts with ERBB2. Interacts (via UIM repeats) with CORO7 (when ubiquitinated at 'Lys-472') (By similarity). Interacts with FCHO1 (By similarity). Interacts with FCHO2. Interacts with SGIP1. Interacts (via EH domains) with DAB2. Interacts (via UIM domains) with UBQLN1 (via ubiquitin-like domain) and can interact with both the ubiquitinated and the non-ubiquitinated forms of UBQLN1. Interacts with UBQLN2 (By similarity). Interacts with REPS2; the interaction is direct (PubMed:10393179). Interacts with EPN1; the interaction is direct (By similarity).|||Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.|||Phosphorylated on serine upon DNA damage, probably by ATM or ATR (By similarity). Phosphorylation on Tyr-850 is involved in the internalization of EGFR. Not required for membrane translocation after EGF treatment or for targeting to coated pits, but essential for a subsequent step in EGFR endocytosis.|||The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.|||The UIM (ubiquitin-interacting motif) repeats specifically bind 'Lys-33'-linked ubiquitin.|||Ubiquitinated.|||clathrin-coated pit http://togogenome.org/gene/10090:Qrich2 ^@ http://purl.uniprot.org/uniprot/Q3V2A7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis (PubMed:30683861). Not detected in heart, brain, kidney, stomach, ovary, liver, lung and uterus.|||Has an essential role in the formation of sperm flagella and flagellar structure maintainance. It acts as a suppressor of ubiquitination and degradation of proteins involved in flagellar development and motility.|||Interacts with AKAP3, ODF2 and TSSK4.|||Knockout mice show coiled, bent, irregular, short or absent flagella, defects of sperm flagellar ultrastructure, a significant reduction in sperm locomotion, and decreased sperm count.|||Nucleus|||Nucleus membrane|||Significant expression begins at postnatal day 15 and reaches a peak at postnatal day 22. Stable and high expression is detected after postnatal day 22.|||flagellum http://togogenome.org/gene/10090:Prickle1 ^@ http://purl.uniprot.org/uniprot/Q3U5C7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prickle / espinas / testin family.|||Interacts with REST.|||Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure (By similarity). Convergent extension is a complex morphogenetic process during which cells elongate, move mediolaterally, and intercalate between neighboring cells, leading to convergence toward the mediolateral axis and extension along the anteroposterior axis. Necessary for nuclear localization of REST. May serve as nuclear receptor (By similarity).|||Nucleus membrane|||cytosol http://togogenome.org/gene/10090:Rnf10 ^@ http://purl.uniprot.org/uniprot/D3Z1N2|||http://purl.uniprot.org/uniprot/H7BX06|||http://purl.uniprot.org/uniprot/Q3UIW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNF10 family.|||Cytoplasm|||E3 ubiquitin-protein ligase that catalyzes monoubiquitination of 40S ribosomal proteins RPS2/us5 and RPS3/us3 in response to ribosome stalling. Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): RNF10 acts by mediating monoubiquitination of RPS2/us5 and RPS3/us3, promoting their degradation by the proteasome. Also promotes ubiquitination of 40S ribosomal proteins in response to ribosome stalling during translation elongation. The action of RNF10 in iRQC is counteracted by USP10 (By similarity). May also act as a transcriptional factor involved in the regulation of MAG (Myelin-associated glycoprotein) expression. Acts as a regulator of Schwann cell differentiation and myelination (By similarity).|||Interacts with MEOX2.|||Nucleus http://togogenome.org/gene/10090:Yod1 ^@ http://purl.uniprot.org/uniprot/Q8CB27 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome membranes decorated with K48-linked ubiquitin chains and remove these chains allowing autophagosome formation.|||Interacts with VCP; the interaction is direct. Interacts with FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on the UBAX-like region, suggesting that it may be indirect. Interacts with PLAA, UBXN6 and VCP; may form a complex involved in macroautophagy.|||The C2H2-type zinc finger mediates specificity for 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains but not for 'Lys-11'-linked ubiquitin chains. Selectivity for 'Lys-11'-linked ubiquitin chains is provided by recognition of the sequence surrounding 'Lys-11' in ubiquitin. The S2 site region provides specificity for longer 'Lys-11'-linked ubiquitin chains.|||The UBAX-like region mediates the interaction with VCP. http://togogenome.org/gene/10090:Prkag1 ^@ http://purl.uniprot.org/uniprot/O54950 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive (By similarity).|||AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity).|||Belongs to the 5'-AMP-activated protein kinase gamma subunit family.|||Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK.|||The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.|||The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 (By similarity). http://togogenome.org/gene/10090:Arnt ^@ http://purl.uniprot.org/uniprot/P53762 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Monomer (PubMed:28602820). Homodimer only upon binding to a DNA (PubMed:26245371, PubMed:28602820). Efficient DNA binding requires dimerization with another bHLH protein (By similarity). Interacts with TACC3 (PubMed:11025203). Interacts with HIF1A, EPAS1, NPAS1 and NPAS3; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371, PubMed:27782878). Forms a heterodimer with AHRR, as well as with other bHLH proteins (PubMed:9887096). Interacts with NOCA7 (By similarity). Interacts with AHR; the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820, PubMed:24001774, PubMed:27782878). Interacts with SIM1 and NPAS4 (PubMed:27782878).|||Nucleus|||Required for activity of the AHR. Upon ligand binding, AHR translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). Not required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex initiates transcription of genes involved in the regulation of a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (By similarity). The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (PubMed:26245371, PubMed:27782878). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820, PubMed:26245371, PubMed:27782878).|||Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens (By similarity). The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (PubMed:26245371, PubMed:27782878). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820).|||Ubiquitous. http://togogenome.org/gene/10090:Gpc4 ^@ http://purl.uniprot.org/uniprot/P51655 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glypican family.|||Cell membrane|||Cell surface proteoglycan that bears heparan sulfate. May be involved in the development of kidney tubules and of the central nervous system.|||Highly expressed in developing brain and kidney.|||Knockout mice have short fore and hind paws, and display a significant decrease in the length of the snout.|||extracellular space http://togogenome.org/gene/10090:Abitram ^@ http://purl.uniprot.org/uniprot/Q80ZQ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein that regulates actin polymerization, filopodia dynamics and increases the branching of proximal dendrites of developing neurons.|||Belongs to the ABITRAM family.|||Detected (at protein level) in liver, lung, heart, spleen, kidney, and ovaries. In brain expression is higher in the hippocampus, the nuclear layer of the cerebellum, the cortex and the caudoputamen.|||Interacts with F-actin (PubMed:24782708). Interacts with G-actin (PubMed:24782708).|||Nucleus|||Nucleus speckle|||dendrite|||growth cone|||lamellipodium http://togogenome.org/gene/10090:Golga7 ^@ http://purl.uniprot.org/uniprot/Q91W53 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ERF4 family.|||Golgi apparatus membrane|||Interacts with GOLGA3. Interacts with ZDHHC9 (By similarity).|||May be involved in protein transport from Golgi to cell surface. The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS (By similarity).|||Palmitoylated on Cys-69 and Cys-72; which is required for Golgi localization and interaction with GOLGA3. http://togogenome.org/gene/10090:Or13l2 ^@ http://purl.uniprot.org/uniprot/Q8VET1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rpl12 ^@ http://purl.uniprot.org/uniprot/P35979|||http://purl.uniprot.org/uniprot/Q5BLK0 ^@ Function|||PTM|||Similarity ^@ Belongs to the universal ribosomal protein uL11 family.|||Binds directly to 26S ribosomal RNA.|||Ubiquitinated at Lys-48 and Lys-83 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling). http://togogenome.org/gene/10090:Bace1 ^@ http://purl.uniprot.org/uniprot/P56818|||http://purl.uniprot.org/uniprot/Q8C4F4 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307 (PubMed:20826464). Acetylation by NAT8 and NAT8B is transient and deacetylation probably occurs in the Golgi. Acetylation regulates the maturation, the transport to the plasma membrane, the stability and the expression of the protein.|||Belongs to the peptidase A1 family.|||Cell membrane|||Cell surface|||Cytoplasmic vesicle membrane|||DXXLL motif is required for a proper endocytosis and retrograde transport to the trans-Golgi network, as well as for regulation of lysosomal degradation.|||Early endosome|||Endoplasmic reticulum|||Endosome|||Expressed in the brain, specifically in neurons and astrocytes (at protein level).|||In brain oxidative stress induced by amyloid-beta deposition during aging increases protein levels.|||Inhibited by RTN3 and RTN4.|||Late endosome|||Lysosome|||Membrane|||Membrane raft|||Mice show a higher mortality rate early in life.|||Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498. Interacts with RTN1; RTN2; RTN3 and RTN4; the interaction leads to inhibition of amyloid precursor protein processing (By similarity). Interacts with SNX6. Interacts with PCSK9. Interacts with NAT8 and NAT8B. Interacts with BIN1 (By similarity). Interacts (via extracellular domain) with ADAM10 (via extracellular domain) (PubMed:29325091). Interacts with SORL1; this interaction may affect binding with APP and hence reduce APP cleavage (PubMed:16407538). Interacts with NRDC AND NRG1 (PubMed:19935654).|||N-Glycosylated (By similarity). Addition of a bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting, further degradation and is required for maintaining stability under stress conditions (PubMed:25592972, PubMed:26467158).|||Palmitoylation mediates lipid raft localization.|||Phosphorylation at Ser-498 is required for interaction with GGA1 and retrograded transport from endosomal compartments to the trans-Golgi network. Non-phosphorylated BACE1 enters a direct recycling route to the cell surface.|||Recycling endosome|||Responsible for the proteolytic processing of the amyloid precursor protein (APP) (PubMed:29325091). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase (PubMed:29325091). Cleaves CHL1 (PubMed:29325091).|||The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP.|||Ubiquitinated at Lys-501, ubiquitination leads to lysosomal degradation. Monoubiquitinated and 'Lys-63'-linked polyubitinated. Deubiquitnated by USP8; inhibits lysosomal degradation.|||axon|||dendrite|||trans-Golgi network http://togogenome.org/gene/10090:Gm20736 ^@ http://purl.uniprot.org/uniprot/J3QNV4|||http://purl.uniprot.org/uniprot/Q497M4 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Apcdd1 ^@ http://purl.uniprot.org/uniprot/Q3U128 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ APCDD1 is transcriptionally regulated by the CTNNB1/TF7L2 complex.|||Belongs to the APCDD1 family.|||Cell membrane|||Expressed during early development of the extraembryonic structures, nervous system, vascular system and inner ear. Also expressed in mesenchyme of various parts of the embryo and in adult hair follicles.|||Homodimer. Interacts with LRP5 and WNT3A (By similarity).|||N-Glycosylated.|||Negative regulator of the Wnt signaling pathway. Inhibits Wnt signaling in a cell-autonomous manner and functions upstream of beta-catenin. May act via its interaction with Wnt and LRP proteins (By similarity). http://togogenome.org/gene/10090:Chd6 ^@ http://purl.uniprot.org/uniprot/A3KFM7|||http://purl.uniprot.org/uniprot/Q8BJ75 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family.|||DNA-dependent ATPase that plays a role in chromatin remodeling. Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin. Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2.|||Interacts with NFE2L2; involved in activation of the transcription.|||Mice with targeted deletion of exon 12 lacking part of the Helicase ATP-binding domain are born in normal Mendelian ratios and are viable. They are fertile and exhibit no obvious morphological or histological difference. However, they display a coordination deficiency which is not due to muscle weakness or bradykinesia.|||Probable cloning artifact. Spurious priming from an intronic poly-A tract.|||Widely expressed.|||nucleoplasm http://togogenome.org/gene/10090:Mrpl11 ^@ http://purl.uniprot.org/uniprot/Q9CQF0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL11 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Rcor3 ^@ http://purl.uniprot.org/uniprot/Q6PGA0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CoREST family.|||May act as a component of a corepressor complex that represses transcription.|||Nucleus http://togogenome.org/gene/10090:Pwwp4c ^@ http://purl.uniprot.org/uniprot/A3KG49 ^@ Similarity ^@ Belongs to the PWWP3A family. http://togogenome.org/gene/10090:Frem1 ^@ http://purl.uniprot.org/uniprot/A2ADN1|||http://purl.uniprot.org/uniprot/Q684R7 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FRAS1 family.|||Defects in Frem1 are the cause of head blebs (heb) which is a spontaneous mutation that is characterized by absent or malformed eyes, which are often open at birth. Cryptophthalmos is noted in all heb homozygous animals, as is occasional hindlimb polydactyly.|||Expressed in epidermis and hair follicles. Expressed in many developing epidermal appendages, including the whisker and sensory vibrissae, cranial and trunk hair follicles, meibomian glands, teeth, footpads, eyelash primordia and invaginating mammary glands. Limb expression localizes to sheets of dermal cells on the apical and basal surfaces of the digits but, unlike FRAS1, is excluded from the apical ectodermal ridge. Usually expressed at higher level in dermal cells underlying the differentiating epithelial components, especially underlying the epidermis of the head, limbs, and eyelids. Expression in the eyelid dermis is apparent as early as 13 dpc. Postnatal expression in the skin is limited to the dermal papillae. In the kidney, it is expressed from 12.5 dpc in the mesenchyme surrounding the branching ureteric tree, with a strong expression in the more proximal regions of these tubules rather than at the proliferating and branching ends of the ureteric buds. In hair follicle, it is selectively expressed in the vibrissal hair primordia during development. Preferentially expressed in the whisker pad epithelia of 12.5 dpc embryos, in both the epithelial and mesenchymal cells of developing hair follicles. In the early stages of hair follicle development (i.e. stages 0-1), it is expressed in both hair placodes and dermal condensations. In stage 2, it is detected in dermal condensations and adjacent epithelia, but not in the upper region of the hair follicles. Expressed at the tip of developing hair follicles in the later stages (i.e. stages 3-5).|||Expressed in the embryos of all stages examined and in some adult tissues including eye, kidney, ovary, urinary bladder and testes; however, the overall expression levels in adult tissues are relatively low compared with those in embryonic tissues.|||Extracellular matrix protein that plays a role in epidermal differentiation and is required for epidermal adhesion during embryonic development.|||Frem1 also corresponds to a N-ethyl-N-nitrosourea-induced allele called 'bat'. Homozygous bat mice display similar phenotype than heb mice.|||Interacts with FREM2.|||The Calx-beta domain binds calcium with high affinity and undergo a major conformational shift upon binding.|||Was termed QBRICK because it contains 12 repeats: 'Q' stands for queen and is taken from the queen being the 12th in a suit of playing card, and 'BRICK' stands for the repeating unit.|||basement membrane http://togogenome.org/gene/10090:Dhx32 ^@ http://purl.uniprot.org/uniprot/Q8BZS9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Ppp4r4 ^@ http://purl.uniprot.org/uniprot/Q8C0Y0 ^@ Function|||Miscellaneous|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Putative regulatory subunit of serine/threonine-protein phosphatase 4.|||Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complex PPP4C-PPP4R4 (By similarity). http://togogenome.org/gene/10090:Hk3 ^@ http://purl.uniprot.org/uniprot/E9Q3Z4|||http://purl.uniprot.org/uniprot/E9Q8S8|||http://purl.uniprot.org/uniprot/Q3TRM8 ^@ Activity Regulation|||Domain|||Function|||Similarity ^@ Belongs to the hexokinase family.|||Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate.|||Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate.|||The N- and C-terminal halves of this hexokinase contain a hexokinase domain. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. http://togogenome.org/gene/10090:Rpl36 ^@ http://purl.uniprot.org/uniprot/P47964 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL36 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm|||cytosol http://togogenome.org/gene/10090:Rc3h2 ^@ http://purl.uniprot.org/uniprot/A2AVP4|||http://purl.uniprot.org/uniprot/P0C090|||http://purl.uniprot.org/uniprot/Q148V4|||http://purl.uniprot.org/uniprot/Q148V5 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binding to dsRNA, but not CDE RNA, crosstalks with the E3 ubiquitin ligase activity and may inhibit ubiquitination.|||HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence.|||Highest levels in lymph node and thymus and slightly lesser amounts in brain, lung, and spleen (at protein level). Very weak expression in heart, muscle, and kidney (at protein level). Expressed in CD4(+) helper T-cells (at protein level).|||Interacts with EDC4 (PubMed:23583643). Interacts with CCR4-NOT deadenylase complex (PubMed:23663784). Interacts with MAP3K5; the interaction is probably stimulus-dependent (By similarity).|||Mutant animals are born at Mendelian ratio, but very few reach adulthood, a large proportion die within the first days after birth. Lethality can be rescued by changing the genetic background from C57BL/6 to outbred NMRI, on which mutant animals appear healthy and fertile, although smaller. Immune cell homeostasis is normal (PubMed:23583643). However, Mice lacking both Rc3h1 and Rc3h2 genes in CD4(+) T-cells develop lymphadenopathy and splenomegaly with increased spleen weight and cellularity, already at young age. They show a prominent lung pathology with a progressive reduction in the alveolar space concomitant with inflammation. They show an average survival of 130 days. CD4(+) T-cells of these mutants show a pronounced bias toward Th17 differentiation (PubMed:23583643, PubMed:25282160).|||P-body|||Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (PubMed:23663784). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation (PubMed:23583643, PubMed:23583642). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (PubMed:25282160). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains. Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains. Involved in the ubiquitination of MAP3K5 (By similarity). Able to interact with double-stranded RNA (dsRNA).|||Proteolytically cleaved by MALT1 in activated CD4(+) T cells; cleavage at Arg-509 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation.|||The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies.|||The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA (PubMed:23663784). It may also be involved in localization to stress granules (By similarity). http://togogenome.org/gene/10090:Lzic ^@ http://purl.uniprot.org/uniprot/Q8K3C3 ^@ Similarity|||Subunit ^@ Belongs to the CTNNBIP1 family.|||Does not interact with CTNNB1. http://togogenome.org/gene/10090:Gmnn ^@ http://purl.uniprot.org/uniprot/O88513|||http://purl.uniprot.org/uniprot/Q3V295 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Absent during G1 phase, accumulates during S, G2, and M phases, and disappears at the time of the metaphase-anaphase transition.|||Belongs to the geminin family.|||Cytoplasm|||Homotetramer (By similarity). Interacts with CDT1; this inhibits binding of the MCM complex to origins of replication (PubMed:12192004, PubMed:15286659, PubMed:15811859). The complex with CDT1 exists in two forms, a 'permissive' heterotrimer and an 'inhibitory' heterohexamer (By similarity). Interacts (via coiled-coil domain) with IDAS (via coiled-coil domain); this targets GMNN to the nucleus (By similarity). The heterodimer formed by GMNN and MCIDAS has much lower affinity for CDT1 than the GMNN homodimer (By similarity). Interacts with a subset of Hox proteins, affinity increasing from anterior to posterior types, the strongest interaction being with HOXB1, HOXC9 and HOXD10 (By similarity). Interacts with LRWD1 from G1/S to mitosis (By similarity).|||Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC) (PubMed:12192004, PubMed:9635433). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle (PubMed:12192004, PubMed:9635433). Inhibits histone acetyltransferase activity of KAT7/HBO1 in a CDT1-dependent manner, inhibiting histone H4 acetylation and DNA replication licensing (By similarity). Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control (By similarity).|||Nucleus|||Phosphorylated during mitosis. Phosphorylation at Ser-181 by CK2 results in enhanced binding to Hox proteins and more potent inhibitory effect on Hox transcriptional activity. http://togogenome.org/gene/10090:Ccndbp1 ^@ http://purl.uniprot.org/uniprot/Q3TVC7 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCNDBP1 family.|||Cytoplasm|||Expressed at high levels in brain, intestine, muscle and ovary and at lower levels in heart, kidney, liver, lung, spleen and testis.|||Expression is induced by partial hepatectomy.|||Highly expressed in the unfertilized egg. Expression is reduced at the two cell and blastocyst stages. Expressed in the liver, CNS and dorsal root ganglia throughout organogenesis. Also expressed in the intestine, kidney, lung, nasal cavities and thymus from 13 dpc.|||Interacts with CCND1 and GRAP2. May also interact with COPS5, RPLP0, SIRT6, SYF2 and TCF3.|||May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription (By similarity). May be required for hepatocyte proliferation.|||Nucleus|||Phosphorylated. http://togogenome.org/gene/10090:Fgf3 ^@ http://purl.uniprot.org/uniprot/Q0VG15 ^@ Similarity ^@ Belongs to the heparin-binding growth factors family. http://togogenome.org/gene/10090:Gsc ^@ http://purl.uniprot.org/uniprot/Q02591 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||By activin.|||In early gastrulation, expressed in the dorsal lip. In later stages of development found in head, limbs and body wall. In the embryo, expressed in the postotic cranial neural crest cells, the frontonasal prominence, the first branchial arch and cleft, and specific regions of large joints.|||Nucleus|||Regulates chordin (CHRD). May play a role in spatial programing within discrete embryonic fields or lineage compartments during organogenesis (By similarity). In concert with NKX3-2, plays a role in defining the structural components of the middle ear; required for the development of the entire tympanic ring. Goosecoid-expressing regions of the gastrulating mouse egg cylinder have organizer-like activity when transplanted into Xenopus embryos. Probably involved in the regulatory networks that define neural crest cell fate specification and determine mesoderm cell lineages in mammals (By similarity). http://togogenome.org/gene/10090:Hrct1 ^@ http://purl.uniprot.org/uniprot/Q9D6B9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or8g24 ^@ http://purl.uniprot.org/uniprot/Q9EQ93 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ucn ^@ http://purl.uniprot.org/uniprot/P81615 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts in vitro to stimulate the secretion of adrenocorticotropic hormone (ACTH) (By similarity). Binds with high affinity to CRF receptor types 1, 2-alpha, and 2-beta (By similarity). Plays a role in the establishment of normal hearing thresholds (PubMed:12091910). Reduces food intake and regulates ghrelin levels in gastric body and plasma (By similarity).|||Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.|||In skin, levels decrease gradually from the telogen (resting) phase of the hair follicle with lowest levels observed in late anagen IV phase of active growth (at protein level).|||In the organ of Corti, detected in the inner hair cell region (at protein level) (PubMed:12091910). Expressed in skin (at protein level) (PubMed:10690896).|||Increased anxiety-like behavior, reduced Crhr2 mRNA levels in the lateral septum, normal basal feeding behavior, and hearing impairment at the level of the inner ear with shorter outer hair cells, higher threshold for auditory stimuli and higher distortion product otoacoustic emissions.|||Interacts with CRHR1 and CRHR2 (via their N-terminal extracellular domain).|||Secreted http://togogenome.org/gene/10090:Lin7a ^@ http://purl.uniprot.org/uniprot/Q8JZS0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the lin-7 family.|||Cell junction|||Cell membrane|||Expressed in the kidney, along the length of the nephron.|||Forms a complex with CASK and CASKIN1 (By similarity). Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (PubMed:10846156). Can also interact with other modular proteins containing protein-protein interaction domains like PALS1, PALS2, MPP7, DLG1, DLG2 and DLG3 through its L27 domain. Interacts with DLG4, GRIN2B and MARCHF11 as well as CDH1 and CTNNB1, the channels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably KCNJ2/Kir2.1 and SLC6A12/BGT-1 via its PDZ domain. The association of LIN7A with cadherin and beta-catenin is calcium-dependent, occurs at synaptic junctions and requires the actin cytoskeleton. Interacts with EGFR, ERBB2, ERBB3 and ERBB4 with both PDZ and KID domains. Associates with KIF17 via APBA1. Interacts with HTR4. Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C) (By similarity).|||Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (PubMed:10846156). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells.|||Postsynaptic density membrane|||The L27 domain mediates interaction with CASK and is involved in the formation of multimeric complexes and the association of LIN7 to membranes.|||The PDZ domain regulates endocytosis and recycling of the receptor at the membrane.|||The kinase interacting site is required for proper delivery of ERBB2 to the basolateral membrane.|||tight junction http://togogenome.org/gene/10090:C1galt1c1 ^@ http://purl.uniprot.org/uniprot/Q9JMG2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with core 1 beta-3-galactosyltransferase (C1GALT1), probably not with the soluble active form.|||Belongs to the glycosyltransferase 31 family. Beta3-Gal-T subfamily.|||Membrane|||Probable chaperone required for the generation of 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins. Probably acts as a specific molecular chaperone assisting the folding/stability of core 1 beta-3-galactosyltransferase (C1GALT1) (By similarity).|||Was originally assigned to be a glycosyltransferase. http://togogenome.org/gene/10090:Cav1 ^@ http://purl.uniprot.org/uniprot/P49817 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adipose tissue, lung, heart, skeletal muscle, stomach, small bowel, kidney, spleen and testis (at protein level).|||Belongs to the caveolin family.|||Cell membrane|||Golgi apparatus membrane|||Homooligomer. Interacts (via the N-terminus) with DPP4; the interaction is direct. Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Interacts with BMX, BTK, CTNNB1, CDH1, GLIPR2, JUP, NOSTRIN, SNAP25 and STX1A. Interacts with SLC7A9. Interacts with TGFBR1 (By similarity). Interacts with CTNNB1, CDH1 and JUP. Interacts with PACSIN2; this interaction induces membrane tubulation (PubMed:21610094). Interacts with CAVIN3 (via leucine-zipper domain) in a cholesterol-sensitive manner. Interacts with EHD2 in a cholesterol-dependent manner (By similarity). Interacts with CAVIN1 (PubMed:19546242). Forms a ternary complex with UBXN6 and VCP; mediates CAV1 targeting to lysosomes for degradation (By similarity). Interacts with ABCG1; this interaction regulates ABCG1-mediated cholesterol efflux (By similarity). Interacts with NEU3; this interaction enhances NEU3 sialidase activity within caveola. Interacts (via C-terminus) with SPRY1, SPRY2 (via C-terminus), SPRY3, and SPRY4 (PubMed:16877379).|||May act as a scaffolding protein within caveolar membranes (By similarity). Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae (PubMed:19546242). Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (By similarity). Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway (PubMed:10816572). Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation (By similarity).|||Membrane raft|||Phosphorylated at Tyr-14 by ABL1 in response to oxidative stress.|||The N-terminus of both isoforms are blocked.|||Ubiquitinated. Undergo monoubiquitination and multi- and/or polyubiquitination. Monoubiquitination of N-terminal lysines promotes integration in a ternary complex with UBXN6 and VCP which promotes oligomeric CAV1 targeting to lysosomes for degradation. Ubiquitinated by ZNRF1; leading to degradation and modulation of the TLR4-mediated immune response.|||caveola|||trans-Golgi network http://togogenome.org/gene/10090:Uaca ^@ http://purl.uniprot.org/uniprot/Q8CGB3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the apoptosome complex, composed of APAF1, pro-caspase-9 and UACA. In the complex, it probably interacts directly with APAF1. Interacts with LGALS3, ARF6 and ACTB. Interacts with RAB39A.|||Cytoplasm|||First detected at 9.5 dpc in heart at the edge of both sides of the common ventricular chamber and is then progressively increased and restricted to the myocardial wall of left common ventricular chamber of heart.|||Highly expressed in heart, liver, kidney and testis. Weakly expressed in lung and skeletal muscle. Not expressed in brain and spleen.|||Mice show a high incidence of inflammatory lesions in preputial glands. Cells around the lesions showed resistance to apoptosis.|||Modulates isoactin dynamics to regulate the morphological alterations required for cell growth and motility. Interaction with ARF6 may modulate cell shape and motility after injury (By similarity). May be involved in multiple neurite formation (PubMed:23624502).|||Nucleus|||Regulates APAF1 expression and plays an important role in the regulation of stress-induced apoptosis. Promotes apoptosis by regulating three pathways, apoptosome up-regulation, LGALS3/galectin-3 down-regulation and NF-kappa-B inactivation. Regulates the redistribution of APAF1 into the nucleus after proapoptotic stress. Down-regulates the expression of LGALS3 by inhibiting NFKB1.|||Up-regulated during cardiomyogenic differentiation. By apoptotic stress in a dose-dependent manner.|||cytoskeleton http://togogenome.org/gene/10090:Nampt ^@ http://purl.uniprot.org/uniprot/Q99KQ4 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NAPRTase family.|||Cytoplasm|||Expression shows a diurnal pattern of oscillation across the 24-hour light-dark cycle in liver, with a reduction in levels before the onset of the dark period (at protein level). Expression shows a diurnal pattern of oscillation in white adipose tissue (WAT), peaking at the beginning of the dark period. Up-regulated during polyclonal immune responses.|||Homodimer.|||Nucleus|||Secreted|||The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma (By similarity). Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression.|||Ubiquitously expressed in lymphoid and non-lymphoid tissues. http://togogenome.org/gene/10090:Prdx5 ^@ http://purl.uniprot.org/uniprot/P99029 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peroxiredoxin family. Prx5 subfamily.|||Cytoplasm|||Mitochondrion|||Monomer.|||Peroxisome matrix|||S-palmitoylated. Depalmitoylated by ABHD10.|||S-palmitoylated. Palmitoylation occurs on the active site, inhibiting its reactivity; therefore PRDX5 palmitoylation status determines its antioxidant capacity.|||The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this atypical 2-Cys Prx, C(R) is present in the same subunit to form an intramolecular disulfide. The disulfide is subsequently reduced by thioredoxin.|||Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events.|||Widely expressed. http://togogenome.org/gene/10090:Taar8b ^@ http://purl.uniprot.org/uniprot/Q5QD06 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Fezf2 ^@ http://purl.uniprot.org/uniprot/Q9ESP5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in the olfactory epithelium, hypothalamus, ventrolateral pallium and prethalamus at mid-gestation. At 12.5 dpc, highly enriched in the postmigratory pyramidal neurons forming the cortical plate situated beneath the pial surface. At 13.5 dpc, expressed in the ventricular zone and subventricular zone at low levels, expression is much higher in the developing cortical plate, where postmitotic neurons are positioned. During late embryonic and early postnatal development, expression disappears from cortical progenitors and becomes restricted to the subplate and the prospective layer V and VI pyramidal neurons.|||Highly expressed in neocortical layer V, moderately expressed in layer VI. Expressed in subcortically projecting neurons.|||In null mutant mice, no subcerebral projection neurons are born and no cortical projections to the brainstem or the spinal cord ever develop. In contrast, other populations of neurons are unaffected. There seems to be a redundant role for FEZF1 and FEZF2 in diencephalon development.|||Nucleus|||Transcription repressor. Required for the specification of corticospinal motor neurons and other subcerebral projection neurons. May play a role in layer and neuronal subtype-specific patterning of subcortical projections and axonal fasciculation. Controls the development of dendritic arborization and spines of large layer V pyramidal neurons. Plays a role in rostro-caudal patterning of the diencephalon and in prethalamic formation. http://togogenome.org/gene/10090:Slc16a8 ^@ http://purl.uniprot.org/uniprot/O35308|||http://purl.uniprot.org/uniprot/Q5UB50 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Deficient mice exhibit significant differences in lactate concentration and pH in the retina and display reduced visual function.|||Expressed exclusively in retinal pigment epithelium and choroid plexus epithelium.|||Lateral cell membrane|||Membrane|||Probable retinal pigment epithelium (RPE)-specific proton-coupled L-lactate transporter (By similarity). May facilitate transport of lactate and H(+) out of the retina and could therefore play an essential role in maintenance of metabolic and ionic homeostasis of the outer retina (PubMed:18524945).|||The two basolateral sorting signals (BLSS) in C-terminal cytoplasmic tails direct SLC16A8 to the basolateral membrane. http://togogenome.org/gene/10090:Il2ra ^@ http://purl.uniprot.org/uniprot/P01590|||http://purl.uniprot.org/uniprot/Q544I2 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Non-covalent dimer of an alpha and a beta subunit. IL2R exists in 3 different forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit). The high and intermediate affinity forms also associate with a gamma subunit.|||Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autoreactive T-cells. http://togogenome.org/gene/10090:Rab11fip5 ^@ http://purl.uniprot.org/uniprot/Q8R361 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds to vesicles enriched in neutral phospholipids via its C2 domain. The interaction is favored by Mg(2+) rather than Ca(2+) (By similarity).|||Cytoplasm|||Early endosome membrane|||Golgi apparatus membrane|||Interacts with RAB11FIP4 (By similarity). Interacts with NAPG (By similarity). Interacts with RO60 (By similarity). Interacts with RAB11A that has been activated by GTP binding (By similarity).|||Mitochondrion membrane|||Phosphorylated on serine and threonine residues. Phosphorylation at Ser-357 is PKA-dependent.|||Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis.|||Recycling endosome membrane|||secretory vesicle membrane http://togogenome.org/gene/10090:Jkamp ^@ http://purl.uniprot.org/uniprot/Q8BI36 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Expressed in numerous tissues, including brain, spleen, thymus, liver, kidney and testis.|||Interacts with RNF5 and MAPK8, but not with MAPK9. Binding to MAPK8 occurs before and after exposure to stress, such as UV irradiation. After exposure to stress, interacts with phosphorylated MAPK8. Competes with DUSP10 for MAPK8 binding (PubMed:16166642, PubMed:19269966). Associates with multiple components of the proteasome and with ERAD regulatory proteins, including AMFR/GP78, CANX, PSMC1, PSMC2, PSMC3/TBP1, PSMC5, PSMC6, PSMD8, SEC61-ALPHA and UFD1 (PubMed:18784250).|||Regulates the duration of MAPK8 activity in response to various stress stimuli (PubMed:16166642). Facilitates degradation of misfolded endoplasmic reticulum (ER) proteins through the recruitment of components of the proteasome and endoplasmic reticulum-associated degradation (ERAD) system (PubMed:18784250).|||Ubiquitinated by RNF5 via 'Lys-63'-linked ubiquitin linkage in a UBE2N-dependent manner. Ubiquitination decreases association with components of the proteasome and ERAD. http://togogenome.org/gene/10090:Stk11ip ^@ http://purl.uniprot.org/uniprot/Q3TAA7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STK11IP family.|||Cytoplasm|||Found in a ternary complex composed of STK11/LKB1, STK11IP and SMAD4 (By similarity). Interacts with SMAD4 (By similarity). Interacts with STK11/LKB1.|||May regulate STK11/LKB1 function by controlling its subcellular localization. http://togogenome.org/gene/10090:Or10a49 ^@ http://purl.uniprot.org/uniprot/Q7TRU4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vwf ^@ http://purl.uniprot.org/uniprot/E9QPU1|||http://purl.uniprot.org/uniprot/Q8CIZ8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ All cysteine residues are involved in intrachain or interchain disulfide bonds.|||Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.|||Multimeric. Interacts with F8 (By similarity).|||Multimeric. Interacts with F8.|||N- and O-glycosylated.|||Plasma. Expressed in liver.|||Platelet deposition and thrombus formation is significantly delayed, but despite this small thrombi do eventually form. At later stages, thrombus growth frequently arrests leaving open channels within arterioles. In double knockouts of FGA and VWF, in addition to delayed platelet deposition, thrombi are fragile and frequently embolize.|||Secreted|||The von Willebrand antigen 2 is required for multimerization of vWF and for its targeting to storage granules.|||extracellular matrix http://togogenome.org/gene/10090:Zkscan8 ^@ http://purl.uniprot.org/uniprot/A0A286YCX3|||http://purl.uniprot.org/uniprot/B2RX01|||http://purl.uniprot.org/uniprot/Q78WV9|||http://purl.uniprot.org/uniprot/Q8BSL0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Rtl1 ^@ http://purl.uniprot.org/uniprot/Q7M732 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Down-regulated during time-course of induced adipogenesis in 3T3L1 cells; Lipid accumulation is unchanged during adipocyte differentiation when Rtl1 is overexpressed.|||Expressed in placenta and in various tissues in late-fetal stage.|||Increased expression throughout development from 9.5 dpc to 18.5 dpc in placenta and, from 12.5 dpc to 15.5 dpc in embryo. Barely detectable in adult brain and midbrains of 14.5 dpc, but abundant at 8.5 dpc.|||Membrane|||Mice suffer from late fetal or neonatal lethality. Mice overexpressing Rtl1 show notable overgrowth and morphological abnormalities of the placenta.|||Plays an essential role in capillaries endothelial cells for the maintenance of feto-maternal interface and for development of the placenta.|||Rtl1 is an imprinted gene located in a cluster of imprinted genes on distal chromosome 12. It is expressed from the paternal chromosome and has an antisense transcript expressed from the maternal chromosome containing 2 microRNAs, mir-136 and mir-127, with full complementarity to Rtl1; mir-136 and mir-127 are processed from an antisense transcript, Rtl1as, and may function as small interfering RNAs to silence Rtl1.|||Rtl1 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes. http://togogenome.org/gene/10090:Ttpal ^@ http://purl.uniprot.org/uniprot/Q9D3D0 ^@ Function ^@ May act as a protein that binds a hydrophobic ligand. http://togogenome.org/gene/10090:Bysl ^@ http://purl.uniprot.org/uniprot/O54825 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bystin family.|||Binds trophinin, tastin and cytokeratins.|||Cytoplasm|||High levels in preimplantation embryos, bone marrow, brain, testis and ovary.|||High levels of maternal transcript in unfertilized eggs. High levels up to blastocyst stage.|||Mice show embryonic lethality around stage 6.5 dpc shortly after implantation. Mice lacking maternal Bysl transcript upon injection of siRNA into fertilized eggs are arrested at the 16-cell stage, fail to induce trophectoderm, and show altered morphology of developing nucleoli. Embryonic stem cells lacking Bysl show accumulation of pre-20S rRNA precursors and a reduction of 40S ribosomal subunits in the cytoplasm.|||Required for processing of 20S pre-rRNA precursor and biogenesis of 40S ribosomal subunits.|||nucleolus http://togogenome.org/gene/10090:Or8b35 ^@ http://purl.uniprot.org/uniprot/Q8VF63 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Spata18 ^@ http://purl.uniprot.org/uniprot/Q0P557 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MIEAP family.|||By p53/TP53 and p63/TP63. Directly activated by p53/TP53.|||Cytoplasm|||In testis, expressed primarily in spermatids.|||Interacts (via coiled-coil domains) with BNIP3L (via BH3 domain). Interacts (via coiled-coil domains) with BNIP3 (via BH3 domain).|||Key regulator of mitochondrial quality that mediates the repairing or degradation of unhealthy mitochondria in response to mitochondrial damage. Mediator of mitochondrial protein catabolic process (also named MALM) by mediating the degradation of damaged proteins inside mitochondria by promoting the accumulation in the mitochondrial matrix of hydrolases that are characteristic of the lysosomal lumen. Also involved in mitochondrion degradation of damaged mitochondria by promoting the formation of vacuole-like structures (named MIV), which engulf and degrade unhealthy mitochondria by accumulating lysosomes. May have a role in spermatogenesis, especially in cell differentiation from late elongate spermatids to mature spermatozoa (By similarity). The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix (By similarity).|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Sik2 ^@ http://purl.uniprot.org/uniprot/Q8CFH6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6 (By similarity).|||Activated by phosphorylation on Thr-175 (By similarity). Inhibited by phosphorylation at Ser-343, Ser-358, Thr-484 and/or Ser-587, probably by PKA, which triggers interaction with 14-3-3 proteins (PubMed:29211348).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Constitutive knockout combined with conditional knockout of SIK3 in the haemopoietic cells results in a severe reduction in peripheral T-cells without reducing B-cell number.|||Cytoplasm|||Interacts with and phosphorylates TORC2/CRTC2 (PubMed:29211348). Interacts (when phosphorylated at Ser-343, Ser-358, Thr-484 and/or Ser-587) with 14-3-3 proteins; the interaction inhibits its kinase activity towards TORCs (PubMed:29211348). There is a cooperative effect of the phosphorylation sites in 14-3-3 binding as the interaction is stronger when more sites are modified.|||Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (By similarity). Phosphorylated at Thr-484 in response to insulin in adipocytes (By similarity). Phosphorylation at Ser-358, Thr-484 and/or Ser-587 following cAMP signaling is required for 14-3-3 interaction and thus inactivation (PubMed:29211348).|||Present in both white and brown adipose tissues with levels increasing during adipocyte differentiation. Lower levels observed in the testis.|||Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:12624099, PubMed:16817901, PubMed:29211348). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction (PubMed:12624099). Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:16817901). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity. In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (By similarity). Also plays a role in thymic T-cell development (PubMed:34732767).|||The RK-rich region is required for cAMP responsiveness. http://togogenome.org/gene/10090:Col4a2 ^@ http://purl.uniprot.org/uniprot/B2RQQ8|||http://purl.uniprot.org/uniprot/P08122 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.|||Belongs to the type IV collagen family.|||Brominated by PXDN.|||Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins (By similarity).|||Contaminating sequence. Potential poly-A sequence starting in position 277.|||Membrane|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Proteolytic processing produces the C-terminal NC1 peptide, canstatin.|||The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.|||There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. Interacts with EFEMP2 (PubMed:17324935).|||Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.|||Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.|||basement membrane http://togogenome.org/gene/10090:Arvcf ^@ http://purl.uniprot.org/uniprot/P98203 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Aberrant splicing.|||Belongs to the beta-catenin family.|||Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as ARVCF (By similarity). Interacts (via the extreme C-terminus) with FRMPD2 (via the PDZ 2 domain). Interacts with CCDC85B (By similarity).|||Contributes to the regulation of alternative splicing of pre-mRNAs.|||Cytoplasm|||Nucleus|||adherens junction http://togogenome.org/gene/10090:Or5p53 ^@ http://purl.uniprot.org/uniprot/Q8VG44 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Hormad2 ^@ http://purl.uniprot.org/uniprot/Q5SQP1 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity. Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes. Required for the DNA double-strand break-independent, BRCA1-dependent activation of ATR on the sex chromosomes that is essential for normal sex body formation.|||Interacts with HORMAD1.|||Male mice are infertile due to spermatocyte loss as a result of characteristic impairment of sex body formation. Spermatocyte apoptosis is confined to the stage IV seminiferous tubules. In contrast to males, female mice are fertile.|||Nucleus|||Phosphorylated in a SPO11-dependent manner.|||Specifically expressed in meiotic germ cells. http://togogenome.org/gene/10090:Ppp1r13l ^@ http://purl.uniprot.org/uniprot/Q5I1X5 ^@ Disease Annotation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the iASPP family.|||Cytoplasm|||Defects in Ppp1r13l are the cause of the waved 3 phenotype, a recessive mutation characterized by abnormalities of the heart and skin. Affected animals have open eyes at birth and hair abnormalities. They develop focal cardiac necrosis at an early age which progresses to fatal dilated cardiomyopathy. This is due to a 14-bp deletion which gives rise to a truncated protein.|||Interacts with TP63 and TP73 (By similarity). Interacts with RELA NF-kappa-B subunit and with SP1 via its C-terminal part. Interacts (via SH3 domain and ANK repeats) with p53/TP53; the interaction inhibits pro-apoptotic activity of p53/TP53 (By similarity).|||Most abundant in skin with high levels also found in heart, testis and stomach. In 15.5 dpc embryonic heart, expressed at higher levels in atria than ventricles.|||Nucleus|||Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (By similarity).|||The ANK repeats and the SH3 domain are required for specific interactions with p53/TP53.|||The N-terminal region is required for cytoplasmic localization. http://togogenome.org/gene/10090:Rgs1 ^@ http://purl.uniprot.org/uniprot/Q9JL25 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in spleen, lymph node and intestine.|||Interacts with GNAI1 and GNAQ.|||Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the N-formylpeptide chemoattractant receptors and leukotriene receptors. Inhibits B cell chemotaxis toward CXCL12 (PubMed:10779778). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form (By similarity).|||cytosol http://togogenome.org/gene/10090:Trim16 ^@ http://purl.uniprot.org/uniprot/Q99PP9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinates via its B-Boxes.|||Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays an essential role in the organization of autophagic response and ubiquitination upon lysosomal and phagosomal damages. Plays a role in the stress-induced biogenesis and degradation of protein aggresomes by regulating the p62-KEAP1-NRF2 signaling and particularly by modulating the ubiquitination levels and thus stability of NRF2. Acts as a scaffold protein and facilitates autophagic degradation of protein aggregates by interacting with p62/SQSTM, ATG16L1 and LC3B/MAP1LC3B. In turn, protects the cell against oxidative stress-induced cell death as a consequence of endomembrane damage.|||Homodimerizes via its coiled-coil domain. Heterodimerizes with MID1, TRIM24 and PML. Interacts with Galectin-3/LGALS3 in a ULK1-dependent manner; this interaction mediates autophagy of damage endomembranes. Interacts with BECN1. Interacts with ATG16L1. Interacts with p62/SQSTM and LC3B/MAP1LC3B.|||Phosphorylated by ULK1.|||Widely expressed. Expressed in basal keratinocytes. http://togogenome.org/gene/10090:Hcrtr2 ^@ http://purl.uniprot.org/uniprot/P58308 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides. Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding.|||The N-terminal region is required for orexin signaling.|||Widely expressed. Isoform 2 not detected in skeletal muscle and kidney. http://togogenome.org/gene/10090:Cited4 ^@ http://purl.uniprot.org/uniprot/A2A7E7|||http://purl.uniprot.org/uniprot/Q9WUL8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as transcriptional coactivator for TFAP2/AP-2. Enhances estrogen-dependent transactivation mediated by estrogen receptors. May function as an inhibitor of transactivation by HIF1A by disrupting HIF1A interaction with CREBBP. May be involved in regulation of gene expression during development and differentiation of blood cells, endothelial cells and mammary epithelial cells.|||Belongs to the CITED family.|||Cytoplasm|||Interacts via its C-terminal region with the CH1 domain of CREBBP and EP300. Interacts with all TFAP2/AP-2 isoforms.|||Nucleus|||Strongly expressed in heart, spleen and testis, and weakly in liver and kidney.|||Undetectable in nulliparous mammary glands but strongly expressed in 11.5 dpc pregnant mammary glands. Strong expression continued until the end of the lactacting stage and then rapidly diminished during the weaning stage. http://togogenome.org/gene/10090:Vmn2r114 ^@ http://purl.uniprot.org/uniprot/E9Q281 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sp110 ^@ http://purl.uniprot.org/uniprot/Q8BVK9 ^@ Disease Annotation|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Contaminating sequence. Potential poly-A sequence.|||Defects in Sp110 are a cause of severely impaired resistance to infection by M.tuberculosis.|||Detected in lung and macrophages.|||May act as a transcription factor. Plays a role in the innate immunity against intracellular pathogens. Required for resistance to M.tuberculosis and L.monocytogenes. Promotes apoptosis of infected cells.|||Nucleus|||Up-regulated after infection with M.tuberculosis. http://togogenome.org/gene/10090:Tmtc4 ^@ http://purl.uniprot.org/uniprot/Q8BG19 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMTC family.|||Endoplasmic reticulum|||Membrane|||Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3. http://togogenome.org/gene/10090:Camsap3 ^@ http://purl.uniprot.org/uniprot/Q80VC9 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAMSAP1 family.|||Cytoplasm|||Expressed at the apical surface of respiratory epithelia, as well as in the acini of submucosal glands (at protein level)(PubMed:32482850). In cochlea, restricted to the organ of Corti and increases during development (at protein level) (PubMed:24244856). Highly expressed in both sensory hair cells and supporting cells (PubMed:24244856).|||Interacts with PLEKHA7 (By similarity). Interacts with CAMSAP2 (PubMed:23169647). Interacts with KATNA1 and KATNB1; leading to regulate the length of CAMSAP3-decorated microtubule stretches (By similarity). Interacts with AKAP9; regulating Golgi assembly in epithelial cells (By similarity). Interacts with MACF1 (By similarity). Interacts with isoform C of CDH23; leading to inhibit CAMSAP3 ability to induce microtubule bundle formation (PubMed:27349180). Interacts with AKNA (PubMed:30787442).|||Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24706919, PubMed:26715742). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24706919). Required for the biogenesis and the maintenance of zonula adherens by anchoring the minus-end of microtubules to zonula adherens and by recruiting the kinesin KIFC3 to those junctional sites (By similarity). Required for orienting the apical-to-basal polarity of microtubules in epithelial cells: acts by tethering non-centrosomal microtubules to the apical cortex, leading to their longitudinal orientation (PubMed:26715742). Plays a key role in early embryos, which lack centrosomes: accumulates at the microtubule bridges that connect pairs of cells and enables the formation of a non-centrosomal microtubule-organizing center that directs intracellular transport in the early embryo (PubMed:28860385). Couples non-centrosomal microtubules with actin: interaction with MACF1 at the minus ends of non-centrosomal microtubules, tethers the microtubules to actin filaments, regulating focal adhesion size and cell migration (By similarity). Plays a key role in the generation of non-centrosomal microtubules by accumulating in the pericentrosomal region and cooperating with KATNA1 to release non-centrosomal microtubules from the centrosome (By similarity). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (By similarity). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (By similarity). Through interaction with AKAP9, involved in translocation of Golgi vesicles in epithelial cells, where microtubules are mainly non-centrosomal (By similarity). Plays an important role in motile cilia function by facilitatating proper orientation of basal bodies and formation of central microtubule pairs in motile cilia (PubMed:32482850).|||Mice are viable but show growth defects (PubMed:26715742). Disorganization of epithelial architecture, characterized by impaired apical-to-basal polarity of microtubules in epithelial cells (PubMed:26715742). Defects in the stereotypic positioning of the nucleus and Golgi apparatus (PubMed:26715742). Mice display subfertility in both sexes and severe nasal airway blockage leading to coughing, sneezing, hyposmia and rhinosinusitis (PubMed:32482850). Majority of cilia lack the central microtubule pair in their axoneme and display disorientated basal bodies and defects in ciliary motion, which is no longer synchronized (PubMed:32482850).|||The CKK domain binds microtubules and specifically recognizes the minus-end of microtubules.|||adherens junction|||cilium axoneme|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Gpr89 ^@ http://purl.uniprot.org/uniprot/Q8BS95 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Golgi pH regulator (TC 1.A.38) family.|||Golgi apparatus membrane|||Homotrimer (By similarity). Interacts with RABL3; the interaction stabilizes GPR89 (PubMed:32220963).|||Voltage dependent anion channel required for acidification and functions of the Golgi apparatus that may function in counter-ion conductance (By similarity). Plays a role in lymphocyte development, probably by acting as a RABL3 effector in hematopoietic cells (PubMed:32220963). http://togogenome.org/gene/10090:Zfp62 ^@ http://purl.uniprot.org/uniprot/Q8C827 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 8.5 dpc, expressed predominantly in neural tube and somites. At 9.5 dpc, expression is higher in the peripheral region of the brain, in the dorsal region of the neural tube, in the segmental plate and in the somites. In developing brain, expression is restricted to regions with actively proliferating cells. At later stages, expressed in many tissues of neuroectodermal and mesodermal origin. At 17 dpc, expression is high in the skeletal muscle fibers, which are mitotically arrested and terminally differentiated.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in skeletal and cardiac muscle.|||May play a role in differentiating skeletal muscle.|||Nucleus http://togogenome.org/gene/10090:Naa11 ^@ http://purl.uniprot.org/uniprot/A8W660|||http://purl.uniprot.org/uniprot/Q3UX61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family. ARD1 subfamily.|||Component of the N-terminal acetyltransferase A (NatA) complex composed of NAA11 and NAA15. Interacts with HIF1A.|||Cytoplasm|||Displays alpha (N-terminal) acetyltransferase activity. Proposed alternative catalytic subunit of the N-terminal acetyltransferase A (NatA) complex.|||Nucleus http://togogenome.org/gene/10090:Yif1b ^@ http://purl.uniprot.org/uniprot/Q9CX30 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YIF1 family.|||Endoplasmic reticulum membrane|||Functions in endoplasmic reticulum to Golgi vesicle-mediated transport and regulates the proper organization of the endoplasmic reticulum and the Golgi (PubMed:26077767, PubMed:33103737). Plays a key role in targeting to neuronal dendrites receptors such as HTR1A (By similarity). Also plays a role in primary cilium and sperm flagellum assembly probably through protein transport to these compartments (PubMed:33103737).|||Golgi apparatus membrane|||Highly expressed in brain. Expressed in Purkinje cells of the cerebellum.|||Homozygous knockout mice lacking Yif1b show impaired visual perception associated with retinal dysfunction and optic atrophy while no ventilator defects or increased susceptibility to seizures is observed. Some deficits in fine motor skills and coordination are also observed. Mutant mice have delayed cerebral myelination, enlarged ventricles, and cerebellar atrophy associated with a reduction in the number of Purkinje cells due to neurodegeneration and necrosis. Purkinje cells show fragmentation of the Golgi apparatus, large autophagosome-like vacuoles, and alteration of the endoplasmic reticulum with dilated cisternae. Male knockout mice are infertile due to abnormal spermatozoa flagella that show microtubule disorganization. Primary cilium abnormalities are also observed in cerebellar Purkinje cells and hippocampal pyramidal cells, for instance.|||Interacts with HTR1A (via C-terminus) (By similarity). Interacts with ABCB9 (via TMD0); this interaction allows (but is not essential) the ER-to-Golgi trafficking and strongly depends on a salt bridge within TMD0 (By similarity). http://togogenome.org/gene/10090:Gtf2b ^@ http://purl.uniprot.org/uniprot/P62915|||http://purl.uniprot.org/uniprot/Q3ULN2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated. Autoacetylated; autoacetylation at Lys-238 stimulates transcription activation.|||Belongs to the TFIIB family.|||Chromosome|||Found in a ternary complex with TATA box-bound TBP. Part of a TFIID-containing RNA polymerase II pre-initiation complex (PIC) that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Associates with TFIID-TFIIA (DA complex) to form TFIID-TFIIA-TFIIB (DAB complex), which is then recognized by RNA polymerase II (Pol II). Found in a RNA polymerase II initiation complex. Interacts (via C-terminus) with TBP; this interaction with TATA box-bound TBP guides Pol II into the PIC. Interacts (via N-terminus) with Pol II. Interacts (via C-terminus) with SSU72; this interaction is inhibited by SYMPK. Interacts with NR2F1; this interaction is direct. Interacts with PGR. Interacts with ESR1. Interacts with GTF2F1 (via C-terminus and preferentially via acetylated form); this interaction prevents binding of GTF2B to GTF2F2. Interacts with GTF2F2 (via N-terminus); this interaction is inhibited in presence of GTF2F1. Interacts with the transcription elongation factor TCEA2. Interacts with HSF1 (via transactivation domain) (By similarity). Interacts with GPBP1 (PubMed:14612417).|||General transcription factor that plays a role in transcription initiation by RNA polymerase II (Pol II). Involved in the pre-initiation complex (PIC) formation and Pol II recruitment at promoter DNA. Together with the TATA box-bound TBP forms the core initiation complex and provides a bridge between TBP and the Pol II-TFIIF complex. Released from the PIC early following the onset of transcription during the initiation and elongation transition and reassociates with TBP during the next transcription cycle. Associates with chromatin to core promoter-specific regions. Binds to two distinct DNA core promoter consensus sequence elements in a TBP-independent manner; these IIB-recognition elements (BREs) are localized immediately upstream (BREu), 5'-[GC][GC][GA]CGCC-3', and downstream (BREd), 5'-[GA]T[TGA][TG][GT][TG][TG]-3', of the TATA box element. Modulates transcription start site selection. Exhibits also autoacetyltransferase activity that contributes to the activated transcription.|||Nucleus|||The TFIIB-type zinc-binding domain is necessary for the interaction and recruitment of RNA polymerase II to the core promoter, the formation of a fully competent pre-initiation complex (PIC) assembly and basal transcription initiation. The C-terminus is necessary and sufficient for interaction with the TATA box-bound TBP complex and for the formation of PIC. http://togogenome.org/gene/10090:Scgb2b1 ^@ http://purl.uniprot.org/uniprot/A0A087WNN9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the secretoglobin family.|||Secreted http://togogenome.org/gene/10090:Txndc8 ^@ http://purl.uniprot.org/uniprot/Q69AB2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the thioredoxin family.|||Cytoplasm|||First expressed after puberty.|||Golgi apparatus|||May be required for post-translational modifications of proteins required for acrosomal biogenesis. May act by reducing disulfide bonds within the sperm (By similarity).|||Testis-specific. Only expressed during spermiogenesis, prominently in the Golgi apparatus of pachytene spermatocytes and round and elongated spermatids, with a transient localization in the developing acrosome of round spermatids (at protein level). http://togogenome.org/gene/10090:Mrpl30 ^@ http://purl.uniprot.org/uniprot/Q9D7N6 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL30 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Nlrp9c ^@ http://purl.uniprot.org/uniprot/Q66X01 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NLRP family.|||Cytoplasm|||May be involved in inflammation.|||Oocyte specific. http://togogenome.org/gene/10090:Sumf1 ^@ http://purl.uniprot.org/uniprot/Q8R0F3 ^@ Caution|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sulfatase-modifying factor family.|||Endoplasmic reticulum lumen|||Mice display frequent early mortality, congenital growth retardation, skeletal abnormalities and neurological defects. Defects are caused by absence of all sulfatases activities. Massive glycosaminoglycans accumulation and cell vacuolization are observed in all tissues and are associated with systemic inflammation, apoptosis and neurodegeneration.|||Monomer, homodimer and heterodimer with SUMF2.|||N-glycosylated. Contains high-mannose-type oligosaccharides.|||Oxidase that catalyzes the conversion of cysteine to 3-oxoalanine on target proteins, using molecular oxygen and an unidentified reducing agent. 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation of arylsulfatases and some alkaline phosphatases that use the hydrated form of 3-oxoalanine as a catalytic nucleophile. Known substrates include GALNS, ARSA, STS and ARSE.|||The catalytic copper is required to activate oxygen and catalyze oxidative C-H activation.|||The enzyme reaction was initially thought to act via a redox-active disulfide bond mechanism; however the disulfide bond only takes place with inactive enzyme that lacks the copper cofactor. The catalytic copper is required to activate oxygen and catalyze oxidative C-H activation. http://togogenome.org/gene/10090:Vmn1r256 ^@ http://purl.uniprot.org/uniprot/K9J7H2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lipo1 ^@ http://purl.uniprot.org/uniprot/F6WYC8 ^@ Similarity ^@ Belongs to the AB hydrolase superfamily. Lipase family. http://togogenome.org/gene/10090:Tnip2 ^@ http://purl.uniprot.org/uniprot/Q99JG7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||In vitro phosphorylated by CHUK.|||Inhibits NF-kappa-B activation by blocking the interaction of RIPK1 with its downstream effector NEMO/IKBKG. Forms a ternary complex with NFKB1 and MAP3K8 but appears to function upstream of MAP3K8 in the TLR4 signaling pathway that regulates MAP3K8 activation. Involved in activation of the MEK/ERK signaling pathway during innate immune response; this function seems to be stimulus- and cell type specific. Required for stability of MAP3K8. Involved in regulation of apoptosis in endothelial cells; promotes TEK agonist-stimulated endothelial survival. May act as transcriptional coactivator when translocated to the nucleus. Enhances CHUK-mediated NF-kappa-B activation involving NF-kappa-B p50-p65 and p50-c-Rel complexes.|||Interacts with STK11/LKB1, TNFAIP3, IKBKG, NFKB1, MAP3K8, TEK, RIPK1, CHUK, IKBKB and SMARCD1. Interacts with polyubiquitin (By similarity).|||Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination probably leading to constitutive proteasomal degradation which can be impaired by IKK-A/CHUK or IKBKB probably involving deubiquitination. Deubiquitinated by USP35; leading to stabilization and inhibition of TNFalpha-induced NF-kappa-B activation.|||Ubiquitously expressed in all tissues examined. http://togogenome.org/gene/10090:Pum1 ^@ http://purl.uniprot.org/uniprot/Q80U78 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Cytoplasmic granule|||During the development of the testis, expressed 2 days postpartum (dpp) and then starts to increase at 14 dpp when pachytene spermatocytes first appear.|||Mice are viable and grow to adulthood without apparent defects except that they are smaller than wild-type mice at 8 weeks of age (PubMed:22342750, PubMed:25768905). Males mice however show significantly reduced sperm counts and fertility: testicular hypoplasia is observed (PubMed:22342750). Heterozygous knockout mice manifest neurological dysfunction, hyperactivity, and progressive cerebellar signs including gross and fine motor incoordination (PubMed:25768905, PubMed:29474920). They show spontaneous seizures, abnormal EEG activity with generalized epileptiform spikes by the age of 16 weeks, and have smaller than normal cerebella (PubMed:29474920).|||P-body|||Phosphorylation at Ser-715 promotes RNA-binding activity. Following growth factor stimulation phosphorylated at Ser-715, promoting binding to the 3'-UTR of CDKN1B/p27 mRNA.|||Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (By similarity). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (By similarity).|||Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation. Also mediates deadenylation-independent repression by promoting accessibility of miRNAs. Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (By similarity). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (By similarity). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (By similarity). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53 (PubMed:22342750). Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (PubMed:24412312). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (By similarity).|||The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface. PUM1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine.|||Widely expressed. Expressed in brain, heart, kidney, liver, lung, skin, intestine, spleen, testis and thymus. Weakly or not expressed in muscles and stomach. Expressed at various stages of myeloid and lymphoid cell development (PubMed:12667987). Highly expressed in testis (PubMed:22342750). Expressed in all major brain regions (at protein level) (PubMed:25768905). http://togogenome.org/gene/10090:Kansl3 ^@ http://purl.uniprot.org/uniprot/A2RSY1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.|||Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.|||Nucleus http://togogenome.org/gene/10090:H2al1k ^@ http://purl.uniprot.org/uniprot/J3QP08 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Tlx1 ^@ http://purl.uniprot.org/uniprot/Q9QX99 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Dapl1 ^@ http://purl.uniprot.org/uniprot/Q9D757 ^@ Developmental Stage|||Function|||Tissue Specificity ^@ Expressed in hair follicle, corneal epithelium, epidermis and footpad epithelium (at protein level).|||May play a role in the early stages of epithelial differentiation or in apoptosis.|||Weakly expressed in outer cells of the two cell-layer ectoderm at embryonic day 14.5. Detected only in the intermediate cells, undetectable in the basal or outermost epidermal cells or the occasional follicular buds. In 17.5 dpc and 18.5 dpc epidermis expression is restricted to a single layer of suprabasal cells and is absent in the granular cell layer. Also present in the differentiated follicular cells at the apex of the 'horseshoeshaped' matrix. Detected throughout the limbal and corneal epithelium at day 1 of postnatal life, at day 5 of post-natal life it was no longer detected in the limbal epithelium. http://togogenome.org/gene/10090:Ywhaz ^@ http://purl.uniprot.org/uniprot/P63101 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB. Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (By similarity). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity).|||Belongs to the 14-3-3 family.|||Cytoplasm|||Homodimer. Heterodimerizes with YWHAE (By similarity). Homo- and heterodimerization is inhibited by phosphorylation on Ser-58 (By similarity). Interacts with FOXO4, NOXA1, SSH1 and ARHGEF2. Interacts with CDK16 and with WEE1 (C-terminal). Interacts with MLF1 (phosphorylated form); the interaction retains it in the cytoplasm. Interacts with BSPRY. Interacts with Thr-phosphorylated ITGB2 (By similarity). Interacts with Pseudomonas aeruginosa exoS (unphosphorylated form). Interacts with BAX; the interaction occurs in the cytoplasm. Under stress conditions, MAPK8-mediated phosphorylation releases BAX to mitochondria. Interacts with phosphorylated RAF1; the interaction is inhibited when YWHAZ is phosphorylated on Thr-232. Interacts with TP53; the interaction enhances p53 transcriptional activity. The Ser-58 phosphorylated form inhibits this interaction and p53 transcriptional activity. Interacts with ABL1 (phosphorylated form); the interaction retains ABL1 in the cytoplasm. Interacts with PKA-phosphorylated AANAT; the interaction modulates AANAT enzymatic activity by increasing affinity for arylalkylamines and acetyl-CoA and protecting the enzyme from dephosphorylation and proteasomal degradation (By similarity). It may also prevent thiol-dependent inactivation (By similarity). Interacts with AKT1; the interaction phosphorylates YWHAZ and modulates dimerization (By similarity). Interacts with GAB2 (By similarity). Interacts with SAMSN1. Interacts with BCL2L11 and TLK2. Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (By similarity). Interacts with ZFP36L1 (via phosphorylated form); this interaction occurs in a p38 MAPK- and AKT-signaling pathways (PubMed:22701344). Interacts with SLITRK1 (By similarity). Interacts with AK5, LDB1, MADD, PDE1A and SMARCB1 (By similarity). Interacts with ARHGEF7 and GIT1 (PubMed:16959763). Interacts with MEFV (By similarity). Interacts with ADAM22 (via C-terminus) (By similarity).|||Melanosome|||The delta, brain-specific form differs from the zeta form in being phosphorylated (Probable). Phosphorylation on Ser-184 by MAPK8; promotes dissociation of BAX and translocation of BAX to mitochondria (By similarity). Phosphorylation on Thr-232; inhibits binding of RAF1 (By similarity). Phosphorylated on Ser-58 by PKA and protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion (PubMed:9705322). Phosphorylation on Ser-58 by PKA; disrupts homodimerization and heterodimerization with YHAE and TP53 (By similarity). http://togogenome.org/gene/10090:Ffar1 ^@ http://purl.uniprot.org/uniprot/Q76JU9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in pancreatic islet beta cells (at protein level) (PubMed:16044321). Expressed in pancreatic islet beta cells.|||G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation (PubMed:23335512). Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway. Mediates the anti-inflammatory effects of omega-3 polyunsaturated fatty acids (PUFAs) via inhibition of NLRP3 inflammasome activation.|||Is also activated by synthetic agonists, such as AM-8182, AM-6331 and TAK-875 (fasiglifam). AM-8182 is a full agonist, while AM-6331 and TAK-875 (fasiglifam) are partial agonists that potentiate the activity of the endogenous ligands, such as alpha-linolenic acid and gamma-linolenic acid.|||No visible phenotype at birth and during the following six weeks. Male mice tend to develop a slightly decreased glucose tolerance after 13 weeks of age, but this is not observed with female mice. Insulin secretion in response to glucose is unchanged in mutant mice, but it is not potentiated by fatty acids, contrary to what is observed with wild-type mice. On the other hand, wild-type and mutant mice display the same inhibition of the first phase of glucose-stimulated insulin secretion after prolonged exposure to fatty acids or exposure to a high-fat diet (PubMed:17395749, PubMed:18559658). Compared to wild-type, mutant mice that are kept on a high-fat diet display a decrease of the second phase of glucose-stimulated insulin secretion (PubMed:18559658). Mutant mice do not display increased secretion of glucagon-like peptide 1 (GLP-1) in response to oral absorption of corn oil and display slightly increased blood glucose levels after oral absorption of corn oil (PubMed:23403053). Besides, mutant mice display decreased bone density (PubMed:23335512). http://togogenome.org/gene/10090:Nucb1 ^@ http://purl.uniprot.org/uniprot/A0A1C7CYU3|||http://purl.uniprot.org/uniprot/Q02819 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nucleobindin family.|||Cytoplasm|||Discovered as DNA-binding protein in the serum of lupus-prone mice.|||Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunits GNAI1, GNAI2 and GNAI3 with higher affinity for GNAI1 and GNAI3 than for GNAI2. Preferentially interacts with inactive rather than active GNAI3. Interaction with GNAI3 is inhibited when NUCB1 binds calcium, probably due to a conformational change which renders the GBA motif inaccessible.|||Lymphoid cells as well as other somatic cells, such as liver and kidney cells.|||Major calcium-binding protein of the Golgi which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates alpha subunits of guanine nucleotide-binding proteins (G proteins) (By similarity).|||Secreted|||The EF-hand domains are unfolded in the absence of Ca(2+) and fold upon Ca(2+) addition.|||The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Chchd2 ^@ http://purl.uniprot.org/uniprot/Q9D1L0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with RBPJ.|||Mitochondrion|||Mitochondrion intermembrane space|||Nucleus|||Transcription factor. Binds to the oxygen responsive element of COX4I2 and activates its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen). http://togogenome.org/gene/10090:Mrpl13 ^@ http://purl.uniprot.org/uniprot/Q9D1P0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL13 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity). Interacts with OXA1L (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Or1r1 ^@ http://purl.uniprot.org/uniprot/Q8VFY0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pigh ^@ http://purl.uniprot.org/uniprot/Q5M9N4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGH family.|||Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts with PIGQ.|||Cytoplasm|||Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. http://togogenome.org/gene/10090:Ndufs6 ^@ http://purl.uniprot.org/uniprot/P52503 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFS6 subunit family.|||Male and female mice are fertile but produce smaller litters and pups have a lower neonatal survival rate (PubMed:22474353). While mice are normal during the first 4 months of life, they are prone to rapid onset weight loss and sudden death after this period (PubMed:22474353). They display cardiomyopathy associated with a doubling of heart weight, impaired systolic function and a reduction in functional capacity (PubMed:22474353). Males are most severely affected, with a propensity to develop cardiac failure and diminished survival after 4 months of age (PubMed:22474353). Defects are due to membrane respiratory chain NADH dehydrogenase (Complex I) deficiency (PubMed:22474353). In the knockout experiment described above, mice show a complete knockout of Ndufs6 subunit in heart resulting in marked complex I deficiency, but small amounts of wild-type Ndufs6 mRNA are still present in other tissues, probably due to tissue-specific mRNA splicing, resulting in milder complex I defects (PubMed:22474353).|||Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:0610030E20Rik ^@ http://purl.uniprot.org/uniprot/Q149G0 ^@ Similarity ^@ Belongs to the UPF0561 family. http://togogenome.org/gene/10090:Rdh9 ^@ http://purl.uniprot.org/uniprot/Q8K5C8 ^@ Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family. http://togogenome.org/gene/10090:Adh5 ^@ http://purl.uniprot.org/uniprot/P28474|||http://purl.uniprot.org/uniprot/Q6P5I3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione. Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate. Class-III ADH is remarkably ineffective in oxidizing ethanol. Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.|||Cytoplasm|||Homodimer.|||Ubiquitous. http://togogenome.org/gene/10090:Selenoo ^@ http://purl.uniprot.org/uniprot/Q9DBC0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SELO family.|||Catalyzes the transfer of adenosine 5'-monophosphate (AMP) to Ser, Thr and Tyr residues of target proteins (AMPylation). May be a redox-active mitochondrial selenoprotein which interacts with a redox target protein.|||Mitochondrion http://togogenome.org/gene/10090:Atg12 ^@ http://purl.uniprot.org/uniprot/Q9CQY1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) May act as a proviral factor. In association with ATG5, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection.|||Acetylated by EP300.|||Belongs to the ATG12 family.|||Cytoplasm|||Forms a conjugate with ATG5 (PubMed:11266458, PubMed:12482611, PubMed:12890687, PubMed:12665549, PubMed:18768753, PubMed:19417210). The ATG12-ATG5 conjugate forms a complex with several units of ATG16L1 (PubMed:12665549). Forms an 800-kDa complex composed of ATG12-ATG5 and ATG16L2 (PubMed:22082872). Interacts with DHX58/RIG-1, IFIH1/MDA5 and MAVS/IPS-1 in monomeric form as well as in ATG12-ATG5 conjugate. The interaction with MAVS is further enhanced upon vesicular stomatitis virus (VSV) infection. Interacts with ATG3 and ATG7 (By similarity). Interacts with ATG10 (PubMed:12482611). Interacts with TECPR1 (By similarity). Interacts with SH3BGRL (By similarity).|||Preautophagosomal structure membrane|||Shares weak sequence similarity with ubiquitin family, but contains an 'ubiquitin superfold' and the C-terminal Gly is required for isopeptide linkage.|||Ubiquitin-like protein involved in autophagy vesicles formation. Conjugation with ATG5 through a ubiquitin-like conjugating system involving also ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes.|||Ubiquitous. http://togogenome.org/gene/10090:Cntn6 ^@ http://purl.uniprot.org/uniprot/Q9JMB8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. Contactin family.|||Cell membrane|||Contactins mediate cell surface interactions during nervous system development. Participates in oligodendrocytes generation by acting as a ligand of NOTCH1. Its association with NOTCH1 promotes NOTCH1 activation through the released notch intracellular domain (NICD) and subsequent translocation to the nucleus (By similarity). Involved in motor coordination.|||Expressed in brain. In brain, it is preferentially expressed in the accessory olfactory bulb, layers II/III and V of the cerebral cortex, piriform cortex, anterior thalamic nuclei, locus coeruleus of the pons and mesencephalic trigeminal nucleus and in Purkinje cells of the cerebellum.|||Highly expressed after birth, reaching a maximum at the postnatal day 7, and declines thereafter in the cerebrum, whereas it increases in the cerebellum to adulthood.|||Interacts with PTPRG.|||Mice are viable and fertile, the formation and organization of all nuclei and layers throughout the brains are apparently normal. They are however slow to learn to stay on the rotating rod in the rotorod test during repeated trials, and display dysfunction of equilibrium and vestibular senses in the wire hang and horizontal rod-walking tests. http://togogenome.org/gene/10090:Ppt2 ^@ http://purl.uniprot.org/uniprot/O35448 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the palmitoyl-protein thioesterase family.|||Expressed throughout the brain, primarily in neurons, and at lower levels in glial cells.|||Lysosome|||Mice are healthy at birth, but develop neuronal abnormalities, infiltration of bone marrow by macrophages and multinucleated giant cells, and splenomegaly caused by extramedullary hematopoiesis. Autofluorescent storage material is present in many cell types, particularly reticuloendothelial cells and neurons.|||Removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. Has the highest S-thioesterase activity for the acyl groups palmitic and myristic acid followed by other short- and long-chain acyl substrates. However, because of structural constraints, is unable to remove palmitate from peptides or proteins (By similarity). http://togogenome.org/gene/10090:Mcidas ^@ http://purl.uniprot.org/uniprot/Q3UZ45 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 12.5 dpc expression is restricted to the developing mouse brain. High levels are detected in the cortical hem and the choroid plexus epithelium in the telencephalic midline by cells starting to differentiate (at protein level).|||Belongs to the geminin family.|||Heterodimer (via coiled-coil domain) with GMNN (via coiled-coil domain); targets GMNN to the nucleus. Can form homodimers (in vitro, via coiled-coil domain), but these are much less stable than the heterodimer formed with GMNN.|||Nucleus|||Transcription regulator specifically required for multiciliate cell differentiation. Acts in a multiprotein complex containing E2F4 and E2F5 that binds and activates genes required for centriole biogenesis. Required for the deuterosome-mediated acentriolar pathway. Plays a role in mitotic cell cycle progression by promoting cell cycle exit. Modulates GMNN activity by reducing its affinity for CDT1. http://togogenome.org/gene/10090:Isl1 ^@ http://purl.uniprot.org/uniprot/A2RSV5|||http://purl.uniprot.org/uniprot/P61372|||http://purl.uniprot.org/uniprot/Q8BTH7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ At neuronal promoters, displaces LDB1 from LHX3 LIM domain to form a ternary complex in which ISL1 contacts both LHX3 and LDB1; allosteric structural changes in the DNA binding domain of LHX3, induced by the ISL1:LHX3 interaction, may explain differences in sequence specificity of the different complexes (PubMed:18583962, PubMed:18539116). Interacts with LHX3 (PubMed:18539116). Interacts (via C-terminus) with POU4F2 (via C-terminus) isoform 1 (PubMed:24643061). Interacts with POU3F2 (PubMed:24643061). Interacts with POU4F3 (PubMed:24643061). Interacts (via N-terminal domain) with MLIP; the interaction represses ISL1 transactivator activity (PubMed:22343712, PubMed:36112854). Interacts with GCN5/KAT2A. Interactions of ISL1 with MLIP1 or KAT2A may be mutually exclusive (PubMed:36112854).|||Between 7.5 dpc and 8.5 dpc, as the heart tube forms, expressed in splanchnic mesenchyme comprising the mesocardium and adjacent to foregut endoderm as well as in both splanchnic mesoderm and in ventral foregut endoderm. At 10 dpc, continues to be expressed in ventral endoderm and splanchnic mesoderm but is not expressed in the myocardium of the heart (PubMed:14667410). At 10.5 dpc, expressed in cardiomyocytes located in the outflow tract (PubMed:22343712).|||DNA-binding transcriptional activator (PubMed:14664703, PubMed:24643061, PubMed:25775587, PubMed:22343712, PubMed:18539116). Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes (PubMed:24643061, PubMed:25775587, PubMed:18539116). Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation (PubMed:25775587). Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina (PubMed:24643061, PubMed:25775587). Involved in the specification of motor neurons in cooperation with LHX3 and LDB1 (PubMed:18583962). Binds to insulin gene enhancer sequences (By similarity). Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (PubMed:14667410).|||Down-regulated by beta-catenin/CTNNB1 in mesenchymal stem cells (at protein level). The down-regulation probably proceeds through ubiquitination by WWP1 E3 ubiquitin ligase and protein degradation.|||Embryonic mutants exhibit growth retardation at approximately 9.5 dpc and die at approximately 10.5 dpc. Between 9.0 dpc and 9.5 dpc hearts are severely abnormal, appear misshapen and unlooped. Hearts are completely missing the outflow tract, right ventricle, and much of the atria (PubMed:14667410). Conditional mutants for retina expression show a decrease in several gene expression levels involved in the differentiation of retinal ganglion cells (RGC) (PubMed:24643061).|||Isoform 1 is phosphorylated.|||Nucleus|||Preferentially expressed in insulinoma cell lines. Expression is much lower than that of isoform 1. Shows relatively higher transcriptional activity than isoform 1.|||Ubiquitinated probably by WWP1 E3 ubiquitin ligase; ubiquitination is followed by protein degradation. http://togogenome.org/gene/10090:Pim2 ^@ http://purl.uniprot.org/uniprot/Q62070|||http://purl.uniprot.org/uniprot/Q8R1Z0 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.|||Induced by a wide range of growth factors and mitogens; IL2, IL3, IL4, IL7,IL9 and by interferon-gamma (IFNG).|||Initiates from CTG codon.|||Interacts with MYC.|||Mice are viable and fertile. Deficient mice shown reduced T-cell activation and expansion in the presence of the serine/threonine protein kinase mTOR inhibitor rapamycin. Triple knockout mice PIM1/PIM2/PIM3 shown a profound reduction in body size at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size.|||Mutagen in position: 61:K->A (loss of kinase activity).|||Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade; this process requires phosphorylation of MAP3K8/COT. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate.|||Widely expressed, with highest expression in spleen, thymus and brain. Expressed in epiphyseal chondrocytes. http://togogenome.org/gene/10090:Tmem182 ^@ http://purl.uniprot.org/uniprot/B2RVY9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM182 family.|||Cell membrane|||Highly expressed in white adipose tissues (WAT), with 10-fold to 20-fold higher levels than in brown adipose tissue (BAT). Also expressed in skeletal muscle, heart and lung. Lower relative levels of expression in kidney, spleen, testis, brain and liver.|||Interacts with ITGB1.|||Mice exhibit significant increases in body weight, muscle mass, muscle fiber number, muscle fiber diameter and myotube formation and an acceleration of skeletal muscle regeneration.|||Negatively regulates myogenesis and skeletal muscle regeneration via its association with ITGB1 (PubMed:34427057). Modulates ITGB1 activation by decreasing ITGB1-LAMB1 interaction and inhibiting ITGB1-mediated intracellular signaling during myogenesis (PubMed:34427057).|||Up-regulated during myoblast differentiation.|||Up-regulated in adipogenesis and also markedly up-regulated during in vitro myogenesis of C2C12 myoblasts to myocytes. http://togogenome.org/gene/10090:Prokr2 ^@ http://purl.uniprot.org/uniprot/E0CY28|||http://purl.uniprot.org/uniprot/Q8K458 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in several regions of the brain, including paraventricular hypothalamic nucleus, dorsal medial hypothalamic nucleus, paratenial thalamic nuclei, paracentral thalamic nucleus, lateral habenular nucleus, lateral septal nucleus, lateral globus pallidus and amygdala. Highest expression seen in paraventricular thalamic nuclei and is also extensively expressed in the suprachiasmatic nucleus.|||Homodimer.|||Membrane|||Receptor for prokineticin 2. Exclusively coupled to the G(q) subclass of heteromeric G proteins. Activation leads to mobilization of calcium, stimulation of phosphoinositide turnover and activation of p44/p42 mitogen-activated protein kinase (By similarity). http://togogenome.org/gene/10090:Ufsp2 ^@ http://purl.uniprot.org/uniprot/Q99K23 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C78 family.|||Cytoplasm|||Endoplasmic reticulum|||Expressed at high level in brain, kidney, stomach, skeletal muscle, liver, pancreas, spleen and testis.|||Interacts with DDRGK1 (PubMed:21228277). Interacts with TRIP4; deufmylates TRIP4 (By similarity).|||Nucleus|||Thiol-dependent isopeptidase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins (PubMed:17182609, PubMed:21228277). Through TRIP4 deufmylation may regulate intracellular nuclear receptors transactivation and thereby regulate cell proliferation and differentiation (By similarity). http://togogenome.org/gene/10090:Tcf20 ^@ http://purl.uniprot.org/uniprot/Q9EPQ8 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain, lung, liver, kidney and testes.|||Homodimer (Probable). Interacts with RNF4 and JUN. Binds to the regulatory region of MMP3.|||Isoform 2 is exclusively expressed at 7-11 days of development. Isoform 1 is found only at low levels in 15-17 days embryos.|||Nucleus|||The atypical PHD domain functions as a negative modulator of cofactor binding.|||Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. http://togogenome.org/gene/10090:Fam98b ^@ http://purl.uniprot.org/uniprot/Q80VD1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM98 family.|||Cytoplasm|||Homodimer. Component of a tRNA-splicing ligase complex. Interacts with FAM98A.|||Nucleus|||Positively stimulates PRMT1-induced protein arginine dimethylated arginine methylation. http://togogenome.org/gene/10090:Ifi209 ^@ http://purl.uniprot.org/uniprot/Q8BV49 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the HIN-200 family.|||Nucleus http://togogenome.org/gene/10090:Sap18b ^@ http://purl.uniprot.org/uniprot/E9Q317 ^@ Similarity ^@ Belongs to the SAP18 family. http://togogenome.org/gene/10090:Elp4 ^@ http://purl.uniprot.org/uniprot/Q9ER73 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELP4 family.|||Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6.|||Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.|||Cytoplasm|||Expressed throughout the cerebellum.|||Nucleus|||The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification. http://togogenome.org/gene/10090:Icam1 ^@ http://purl.uniprot.org/uniprot/P13597|||http://purl.uniprot.org/uniprot/Q3U8M7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. ICAM family.|||Expressed at low level on a subpopulation of lymphocytes, macrophages, and endothelial cells, but is strongly induced on these cells, and on fibroblasts and epithelial cells.|||Homodimer. Interacts with MUC1 and promotes cell aggregation in epithelial cells. Interacts with ARHGEF26/SGEF. Interacts (on T cell side) with CD81, CD247 and CD9 at immunological synapses between antigen-presenting cells and T cells.|||ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation (By similarity).|||Membrane|||Monoubiquitinated, which is promoted by MARCH9 and leads to endocytosis.|||Spontaneous onset of obesity in 16-week old mice with higher levels of white and brown fat and a slightly heavier liver. Enhanced susceptibility to high fat diet-induced obesity characterized by a weight increase and higher levels of white and brown fat. http://togogenome.org/gene/10090:Rps27 ^@ http://purl.uniprot.org/uniprot/Q6ZWU9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS27 family.|||Binds 1 zinc ion per subunit.|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Required for proper rRNA processing and maturation of 18S rRNAs (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Pwwp2b ^@ http://purl.uniprot.org/uniprot/E9Q9M8 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes (PubMed:30228260). Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z (By similarity). Plays a role in facilitating transcriptional elongation through regulation of histone acetylation (PubMed:30228260). Negatively regulates brown adipocyte thermogenesis by interacting with and stabilizing HDAC1 at the UCP1 gene promoter, thereby promoting histone deacetylation at the promoter leading to the repression of UCP1 expression (PubMed:34180153).|||Component of a MTA1-specific subcomplex of the NuRD complex composed of PWWP2B, MTA1 and HDAC1 but does not contain CHD4 and MBD3 (By similarity). Interacts with MTA1, MTA2, MTA3, HDAC1, HDAC2, RBBP4, RBBP7, BRCC3 and ZNF516 (PubMed:34180153). Does not interact with CHD4 and MBD3 (By similarity).|||Deubiquitinated by BRCC3; leading to its stabilization.|||Expressed in the brown adipose tissue.|||Induced in response to cold.|||Nucleus http://togogenome.org/gene/10090:Ct55 ^@ http://purl.uniprot.org/uniprot/Q14BQ3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed during spermatogenesis, with highest expression in late spermatids. Detected in the cytoplasm of spermatocyte and spermatogonia. Also found in acrosome or flagellum in early and late spermatids (at protein level).|||Expressed in spermatozoa (at protein level).|||Interacts with GABARAP; this interaction may be important for GABARAP protein stability (By similarity). Interacts with LAMP2; this interaction may be important for LAMP2 protein stability (By similarity).|||Knockout mice do not exhibit any gross abnormalities and survive to adulthood. Homozygous females are fertile, while the numbers of both litters and pups progressively decrease in hemizygous males over time. Males are totally infertile around 32 weeks of age.|||Plays a role in spermatogenesis, possibly acting in the regulation of the autophagy pathway.|||acrosome|||flagellum http://togogenome.org/gene/10090:Tax1bp1 ^@ http://purl.uniprot.org/uniprot/Q3UKC1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expressed at 11.5 dpc and 12.5 dpc in distal limb and genital bud.|||Homooligomer. Interacts with TNFAIP3. Interacts with STARD13. Interacts with MYO6. Interacts with TOM1; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and TAX1BP1. Interacts with MAVS; this interaction induces MAVS polyubiquitination. Interacts with TNIP1. Interacts with TRAF6; this interaction mediates deubiquitination of TRAF6 and inhibition of NF-kappa-B activation. Interacts with RIPK1; this interaction negatively regulates RIPK1 ubiquitination (PubMed:18239685). Interacts with NBR1. Interacts with TBK1. Interacts with RB1CC1. Interacts with SQSTM1. Interacts with AZI2.|||Mice genetically knocked out for TAX1BP1 show no obvious abnormalities at birth, but develop age-dependent inflammatory cardiac valvulitis, die prematurely, and are hypersensitive to low doses of TNF-alpha and IL-1beta (PubMed:18239685). In addition, TAX1BP1 deletion impairs clearance of ubiquitinated protein aggregates (PubMed:33207181).|||Mitochondrion|||Phosphorylated in the C-terminal region by CHUK/IKKA leading to NF-kappa-B signaling down-regulation.|||Preautophagosomal structure|||The C-terminal UBZ-type zinc fingers function as ubiquitin-binding domains.|||Ubiquitin-binding adapter that participates in inflammatory, antiviral and innate immune processes as well as selective autophagy regulation (PubMed:18239685, PubMed:33207181). Plays a key role in the negative regulation of NF-kappa-B and IRF3 signalings by acting as an adapter for the ubiquitin-editing enzyme A20/TNFAIP3 to bind and inactivate its substrates. Disrupts the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKBKE to attenuate 'Lys63'-linked polyubiquitination of TBK1 and thereby IFN-beta production (By similarity). Recruits also A20/TNFAIP3 to ubiquitinated signaling proteins TRAF6 and RIPK1, leading to their deubiquitination and disruption of IL-1 and TNF-induced NF-kappa-B signaling pathways (PubMed:18239685). Inhibits virus-induced apoptosis by inducing the 'Lys-48'-linked polyubiquitination and degradation of MAVS via recruitment of the E3 ligase ITCH, thereby attenuating MAVS-mediated apoptosis signaling (By similarity). As a macroautophagy/autophagy receptor, facilitates the xenophagic clearance of pathogenic bacteria such as Salmonella typhimurium and Mycobacterium tuberculosis. Upon NBR1 recruitment to the SQSTM1-ubiquitin condensates, acts as the major recruiter of RB1CC1 to these ubiquitin condensates to promote their autophagic degradation (By similarity).|||autophagosome http://togogenome.org/gene/10090:Smim5 ^@ http://purl.uniprot.org/uniprot/Q8BT42 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tmem176a ^@ http://purl.uniprot.org/uniprot/Q9DCS1 ^@ Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM176 family.|||Interacts with MCOLN2.|||Membrane|||Specifically expressed in lung, kidney and spleen.|||Up-regulated in kidney upon proteinuria. http://togogenome.org/gene/10090:H2-Q9 ^@ http://purl.uniprot.org/uniprot/Q52PG7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Parp2 ^@ http://purl.uniprot.org/uniprot/O88554 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition. Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences. CHD1L promotes PARP2 removal from chromatin.|||Acetylation reduces DNA binding and enzymatic activity.|||At stage 12.5 dpc, expressed at high level in the developing liver and kidneys (PubMed:11948190). At 18.5 dpc, preferentially expressed in the thymus and in regions of the nervous system (PubMed:11948190). Within the developing trunk, preferential expression persisted in the liver and became restricted to the cortical region of the kidney, spleen, adrenal gland, and to stomach and intestinal epithelia (PubMed:11948190). From 14.5 dpc to 18.5 dpc, as well as in the adult, expressed at the highest level in thymus (PubMed:11948190). Expression is particularly high in the subcapsular zone of the thymus where immature lymphocytes proliferate (PubMed:11948190).|||Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP2-HPF1 complex from chromatin (By similarity). Poly-ADP-ribosylated by PARP1 (PubMed:11948190).|||Belongs to the ARTD/PARP family.|||By high levels of DNA-damaging agents.|||Chromosome|||Component of a base excision repair (BER) complex, containing at least XRCC1, PARP1, POLB and LRIG3 (PubMed:11948190). Homo- and heterodimer with PARP1 (By similarity). Interacts (via the PARP catalytic domain) with HPF1 (By similarity). Interacts with core nucleosomes.|||No visible phenotype in normal conditions, but mutant mice are sensitive to ionizing radiation (PubMed:12727891). Following alkylating agent treatment, cells show increased post-replicative genomic instability, G2/M accumulation and chromosome missegregation accompanying kinetochore defects (PubMed:12727891). Mice lacking both Parp1 and Parp2 are not viable and die at the onset of gastrulation (PubMed:12727891). Female mice lacking both Parp1 and Parp2 in the uterus display infertility; defects are caused by decidualization failure and pregnancy loss (PubMed:34580230).|||Nucleus|||Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:12065591). Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:12065591). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (By similarity). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (By similarity). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (By similarity). PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (By similarity). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (By similarity). Specifically mediates formation of branched poly-ADP-ribosylation (By similarity). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex (By similarity).|||Proteolytically cleaved by caspase-8 (CASP8) in response to apoptosis, leading to its inactivation.|||The N-terminal disordered region does not act as a key DNA-binding domain. The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage.|||The N-terminal region (NTR) recognizes and binds poly-ADP-ribose chains produced by PARP1, leading to its recruitment to DNA damage sites.|||The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition.|||The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation. The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins.|||Widely expressed; the highest levels were in testis followed by ovary (PubMed:11133988). Expression is correlated with proliferation, with higher levels occurring during early fetal development and organogenesis and in the highly proliferative cell compartments of adult (PubMed:11948190). http://togogenome.org/gene/10090:Slco3a1 ^@ http://purl.uniprot.org/uniprot/Q8R3L5 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basal cell membrane|||Basolateral cell membrane|||Belongs to the organo anion transporter (TC 2.A.60) family.|||By androgens in kidney and lung.|||In a cholestasis model, mutant mice show decreased survival rate associated with excessive accumulation of bile acids in liver.|||Putative organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormone L-thyroxine, prostanoids such as prostaglandin E1 and E2, bile acids such as taurocholate, glycolate and glycochenodeoxycholate and peptide hormones such as L-arginine vasopressin, likely operating in a tissue-specific manner (By similarity). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable).|||Widely expressed. http://togogenome.org/gene/10090:Chp1 ^@ http://purl.uniprot.org/uniprot/P61022 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calcineurin regulatory subunit family. CHP subfamily.|||Both N-myristoylation and calcium-mediated conformational changes are essential for its function in exocytic traffic. N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes (By similarity).|||Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membranes. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium-dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner (By similarity).|||Cell membrane|||Cytoplasm|||Endomembrane system|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Membrane|||Monomer. Interacts with STK17B; the interaction occurs in a calcium-independent manner and induces the translocation of CHP1 from the Golgi to the nucleus. Interacts with GAPDH; the interaction is direct, occurs in a N-myristoylation-dependent manner and facilitates the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the C-terminal end of the kinesin-motor domain); the interaction occurs in a calcium-dependent manner. Associates (via C-terminal domain) with microtubules; the association occurs with polymerized microtubules during the cell cycle in a myristoylation- and calcium-independent manner and is enhanced by GAPDH. Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the cytoplasmic C-terminal domain); the interaction occurs at the plasma membrane in a calcium-dependent manner and at a domain that is critical for growth factor stimulation of the exchanger (By similarity). Interacts with SLC9A3; increases SLC9A3 trafficking and activity at the plasma membrane (By similarity).|||Nucleus|||Phosphorylated; decreased phosphorylation is associated with an increase in SLC9A1/NHE1 Na(+)/H(+) exchange activity. Phosphorylation occurs in serum-dependent manner. The phosphorylation state may regulate the binding to SLC9A1/NHE1 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Smarcb1 ^@ http://purl.uniprot.org/uniprot/Q3UDA4|||http://purl.uniprot.org/uniprot/Q6ZWP4|||http://purl.uniprot.org/uniprot/Q9Z0H3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF5 family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57 SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (PubMed:26601204). Binds to double-stranded DNA. Interacts with CEBPB (when not methylated) (PubMed:20111005). Interacts with PIH1D1. Interacts with MYK and MAEL (PubMed:16787967). Interacts with PPP1R15A (By similarity). Interacts with DPF2 (By similarity). Interacts with YWHAZ (By similarity). Interacts with ERCC6 (By similarity). Interacts with FOS, FOSB isoform 1 and 2, FOSL1 and FOSL2 (PubMed:29272704).|||Core component of the BAF (SWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.|||Expressed ubiquitously throughout the developing spinal cord, brain and other embryonic tissues at 10.5 dpc-16.5 dpc.|||Nucleus|||The N-terminal DNA-binding region is structurally similar to winged helix domains. http://togogenome.org/gene/10090:Sipa1l1 ^@ http://purl.uniprot.org/uniprot/Q8C0T5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with DLG4, PDLIM5, PDLIM7 and LZTS3. Interacts with the actin cytoskeleton (By similarity). Interacts (via PDZ domain) with EPHA4 (via PDZ motif); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases.|||Phosphorylated at Ser-1328 by CDK5, creating a docking site for the POLO box domains of PLK2. Subsequently, PLK2 binds and phosphorylates SIPA1L1, leading to ubiquitination and degradation by the proteasome (By similarity).|||Postsynaptic density|||Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity).|||Ubiquitinated and degraded by the SCF(BTRC) following phosphorylation by PLK2.|||cytoskeleton|||synaptosome http://togogenome.org/gene/10090:Krtap5-5 ^@ http://purl.uniprot.org/uniprot/Q2TA51 ^@ Function|||Similarity|||Subunit ^@ Belongs to the KRTAP type 5 family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:B9d1 ^@ http://purl.uniprot.org/uniprot/Q9R1S0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the B9D family.|||Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling.|||Mice display impaired cilia formation associated with renal cystic dysplasia, as well as ductal plate malformation of the liver and polydactyly. Additional phenotypes, occurring at varying frequencies, include randomized heart looping, holoprosencephaly, microphthalmia, cleft palate, ventricular septal defect and thinning of the myocardial wall. Depending on their genetic background, mutant mice die between 14.5 dpc and P1.|||Part of the tectonic-like complex (also named B9 complex).|||Specifically or prominently expressed in mouse blastocysts compared to 4-cell stage embryos.|||cilium basal body http://togogenome.org/gene/10090:Scn4a ^@ http://purl.uniprot.org/uniprot/G3X8T7|||http://purl.uniprot.org/uniprot/Q9ER60 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.4/SCN4A subfamily.|||Cell membrane|||Channel activity is regulated by the ancillary beta subunit SCN1B. SCN1B strongly enhances the presence of the pore-forming alpha subunit at the cell surface (By similarity). Interaction with SCN1B is required for rapid channel inactivation and rapid recovery after inactivation, and prevents decrease of channel activity in response to repetitive, high-frequency depolarizations (By similarity). The channel is inhibited by tetrodotoxin (PubMed:11834499).|||Component of a voltage-sensitive sodium channel complex that consists of a pore-forming alpha subunit and one or more regulatory beta subunits. Interacts with SCN1B (By similarity). Heterooligomer with SCN2B or SCN4B; disulfide-linked (By similarity). Interacts with the PDZ domain of the syntrophins SNTA1, SNTB1 and SNTB2 (PubMed:9412493). Interacts with the conotoxin GVIIJ (By similarity).|||Detected in quadriceps muscle (at protein level) (PubMed:18317596). Detected in hind-limb skeletal muscles, but not in heart or brain (PubMed:18317596). Detected at low levels in the myocardium.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Membrane|||Phosphorylation at Ser-1322 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.|||Pore-forming subunit of a voltage-gated sodium channel complex through which Na(+) ions pass in accordance with their electrochemical gradient. Alternates between resting, activated and inactivated states (PubMed:11834499). Required for normal muscle fiber excitability, normal muscle contraction and relaxation cycles, and constant muscle strength in the presence of fluctuating K(+) levels (PubMed:18317596, PubMed:21881211).|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Myadm ^@ http://purl.uniprot.org/uniprot/O35682|||http://purl.uniprot.org/uniprot/Q0VE46 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MAL family.|||Membrane http://togogenome.org/gene/10090:Hnmt ^@ http://purl.uniprot.org/uniprot/A2AQK4|||http://purl.uniprot.org/uniprot/Q91VF2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.|||Cytoplasm|||Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.|||Monomer. http://togogenome.org/gene/10090:Cdcp2 ^@ http://purl.uniprot.org/uniprot/Q8BQH6 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Tmx2 ^@ http://purl.uniprot.org/uniprot/D3Z2J6|||http://purl.uniprot.org/uniprot/Q9D710 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Endoplasmic reticulum and mitochondria-associated protein that probably functions as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. Indirectly regulates neuronal proliferation, migration, and organization in the developing brain.|||Endoplasmic reticulum membrane|||Membrane|||Mitochondrion membrane|||Monomer (By similarity). Homodimer; disulfide-linked (By similarity). Occurs in both reduced and oxidized monomeric form (By similarity). Oxidative conditions increase homodimerization (By similarity). Interacts with CANX (By similarity). Interacts with ATP2A2 (By similarity).|||The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins.|||The thioredoxin domain lacks the 2 redox-active cysteines, suggesting that it lacks thioredoxin activity. http://togogenome.org/gene/10090:Actl6a ^@ http://purl.uniprot.org/uniprot/Q505L1|||http://purl.uniprot.org/uniprot/Q9Z2N8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the actin family.|||Component of numerous complexes with chromatin remodeling and histone acetyltransferase activity. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3 (Probable). Component of the BAF53 complex, at least composed of ACTL6A/BAF53A, RUVBL1/TIP49, SMARCA2/BRM/BAF190B and TRRAP/PAF400, and which may also include a HAT activity related to, but distinct from, that of KAT5. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (By similarity). Interacts with SMARCA4/BRG1/BAF190A (By similarity). Interacts with PHF10/BAF45A (PubMed:17640523). Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80 (By similarity). Interacts with DPF2 (By similarity).|||Expressed predominantly in 10.5 dpc-11.5 dpc neural cells. In the developing spinal cord (10.5 dpc-16.5 dpc), is specifically expressed in proliferating neural progenitors of the ventricular zone. In the developing forebrain and cerebellar primordium, expression is restricted to proliferating neuroepithelial progenitors and cerebellar granule precursors.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Required for maximal ATPase activity of SMARCA4/BRG1/BAF190A and for association of the SMARCA4/BRG1/BAF190A containing remodeling complex BAF with chromatin/nuclear matrix. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (PubMed:17640523). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Putative core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair (By similarity).|||Nucleus|||Widely expressed. Expressed selectively in neural stem and progenitor cells (at protein level). http://togogenome.org/gene/10090:Kctd16 ^@ http://purl.uniprot.org/uniprot/Q5DTY9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization.|||Expressed in the brain, mainly in the hippocampus.|||Homopentamer; forms an open pentamer (By similarity). In contrast to other BTB domain-containing proteins, does not interact with CUL3 (By similarity). Interacts as a tetramer with GABRB1 and GABRB2 (PubMed:20400944).|||Postsynaptic cell membrane|||Presynaptic cell membrane http://togogenome.org/gene/10090:Rpl7 ^@ http://purl.uniprot.org/uniprot/P14148|||http://purl.uniprot.org/uniprot/Q5M9N8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL30 family.|||Component of the large ribosomal subunit (PubMed:36517592). Homodimer (By similarity). Interacts with DHX33 (PubMed:26100019).|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Binds to G-rich structures in 28S rRNA and in mRNAs (By similarity). Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs (By similarity).|||Cytoplasm http://togogenome.org/gene/10090:Vcan ^@ http://purl.uniprot.org/uniprot/E9PYH0|||http://purl.uniprot.org/uniprot/E9QMK2|||http://purl.uniprot.org/uniprot/E9QMK3|||http://purl.uniprot.org/uniprot/G3XA35|||http://purl.uniprot.org/uniprot/Q8BS97 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the aggrecan/versican proteoglycan family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||extracellular matrix http://togogenome.org/gene/10090:Pdia3 ^@ http://purl.uniprot.org/uniprot/P27773 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum|||Endoplasmic reticulum lumen|||In caput and cauda epididymal spermatozoa, detected in the acrosome and principal piece (at protein level).|||Melanosome|||Part of the major histocompatibility complex class I (MHC I) peptide loading complex composed of TAP1, TAP2, B2M, MHC heavy chain, TAPBP, PDIA3, and CALR. Interacts with ERP27 and CANX. Interacts with SERPINA2 and with SERPINA1 (By similarity). Interacts with ATP2A2 (PubMed:23395171).|||Phosphorylated.|||Protein disulfide isomerase that catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins and functions as a protein folding chaperone. Core component of the major histocompatibility complex class I (MHC I) peptide loading complex where it functions as an essential folding chaperone for TAPBP. Through TAPBP, assists the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. Therefore, plays a crucial role in the presentation of antigens to cytotoxic T cells in adaptive immunity.|||Was originally thought to be a phosphatidylinositol 4,5-bisphosphate phosphodiesterase type I (phospholipase C-alpha).|||Within the major histocompatibility complex class I (MHC I) peptide loading complex forms reversible disulfide-linked heterodimers with TAPBP as part of its protein folding chaperone activity. This is essential to assist the dynamic assembly of the MHC I complex with high affinity antigens in the endoplasmic reticulum. http://togogenome.org/gene/10090:Shroom3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1H8|||http://purl.uniprot.org/uniprot/A0A286YDQ8|||http://purl.uniprot.org/uniprot/E9QMY5|||http://purl.uniprot.org/uniprot/Q9QXN0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||At 8.75 dpc, strongly expressed in the cranial neuroepithelium, and also expressed in neural tube, paraxial mesoderm and gut. At 10.5 dpc, expressed in neural tube, forebrain, somites, ventral body wall, heart and gut. At 14.5 dpc, expression is restricted to skeletal muscle, tips of the digits and forebrain.|||Belongs to the shroom family.|||Controls cell shape changes in the neuroepithelium during neural tube closure (PubMed:10589677, PubMed:14680628). Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers (PubMed:14680628, PubMed:16249236, PubMed:16684770, PubMed:22493320). Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays (By similarity).|||Death at birth due to defects in neural tube closure causing exencephaly, acrania, facial clefting and spina bifida.|||Interacts with F-actin (PubMed:10589677). Interacts with ROCK1 (PubMed:22493320).|||The ASD1 domain mediates F-actin binding.|||The ASD2 domain mediates the interaction with ROCK1 and is required for apical constriction induction.|||adherens junction|||cytoskeleton http://togogenome.org/gene/10090:Abhd6 ^@ http://purl.uniprot.org/uniprot/Q8R2Y0 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abhd6 partial knockdown inducing a stronger depletion in liver, kidney and white adipose tissues protects mice against hight-fat diet-induced metabolic disorder and obesity. De novo lipogenesis in liver is reduced and associated with a reduced expression of lipogenic genes. Accumulation of phospholipids and lysophospholipds in the liver is also observed.|||Belongs to the AB hydrolase superfamily.|||Late endosome membrane|||Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol (PubMed:18096503, PubMed:20657592). Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways (PubMed:18096503, PubMed:20657592). Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids (PubMed:24095738). Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism (PubMed:26491015). BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting (PubMed:26491015).|||Lysosome membrane|||Mitochondrion membrane|||Up-regulated in small intestine and liver by high-fat diet.|||Widely expressed with higher expression in small intestine, liver and brown adipose tissue (PubMed:24095738). In brain, expressed postsynaptically in cortical neurons but not detected in microglia (at protein level) (PubMed:20657592). http://togogenome.org/gene/10090:Wnt1 ^@ http://purl.uniprot.org/uniprot/P04426|||http://purl.uniprot.org/uniprot/Q3UR96 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A palmitoylation site was proposed at Cys-93, but it was later shown that this cysteine is engaged in a disulfide bond.|||Accumulates throughout the neural plate at the anterior head folds of the 9 day embryo but only at its lateral tips in more posterior regions. Following neural tube closure, expression is restricted to specific regions of the dorsal wall of the brain ventricles and spinal cord, the ventral wall of the midbrain and the diencephalon, and the lateral walls of the neuroepithelium at the midbrain-hindbrain junction.|||Belongs to the Wnt family.|||Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Interacts with PORCN (PubMed:10866835). Interacts with RSPO1, RSPO2 and RSPO3 (PubMed:16543246). Interacts with WLS (PubMed:19841259).|||Important perinatal lethality, due to defects in brain development. After 14.5 dpc, embryos display dramatic malformations of the mesencephalon and metencephalon, and especially the cerebellum. They show mild midbrain hydrocephaly by 17.5 dpc. Only one out of ten live-born pups survives more than 30 days; these mice respond normally to light, sound, smell and touch, but display severe ataxia.|||Ligand for members of the frizzled family of seven transmembrane receptors.|||Ligand for members of the frizzled family of seven transmembrane receptors. Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (By similarity). In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling (PubMed:15454084, PubMed:16116452). Plays an essential role in the development of the embryonic brain and central nervous system (CNS) (PubMed:2202907, PubMed:16116452). Has a role in osteoblast function, bone development and bone homeostasis (By similarity).|||Many mouse mammary tumors induced by mouse mammary tumor virus (MMTV) contain a provirus integrated into a host cell region which has been named INT-1 (now Wnt1).|||Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface (By similarity). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway (By similarity).|||Secreted|||Testis and mid-gestational embryos. In the testis, detected only in postmeiotic germ cells undergoing differentiation from round spermatids into mature spermatozoa. In the embryos, expression is restricted to the developing CNS in regions of the neural tube other than the telencephalon. Expressed in osteoblast; expression levels increase with advancing osteoblast differentiation. Expressed in the brain, femur, spleen, and hematopoietic bone marrow.|||extracellular matrix http://togogenome.org/gene/10090:Wscd2 ^@ http://purl.uniprot.org/uniprot/D4PHA7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WSCD family.|||Golgi apparatus membrane|||May be due to an intron retention.|||Sialate:O-sulfotransferase which catalyzes 8-O-sulfation at the Sia-glycan level using 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a donor, forming 8-O-sulfated Sia (Sia8S)-glycans. http://togogenome.org/gene/10090:Il10 ^@ http://purl.uniprot.org/uniprot/A0A7R8GUQ3|||http://purl.uniprot.org/uniprot/P18893|||http://purl.uniprot.org/uniprot/Q3U879 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-10 family.|||Homodimer. Interacts with IL10RA and IL10RB.|||Immune regulatory cytokine.|||Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha. Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation (By similarity). In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling (By similarity) (PubMed:28473584).|||Secreted http://togogenome.org/gene/10090:Scgb1b2 ^@ http://purl.uniprot.org/uniprot/O35176 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Sirt7 ^@ http://purl.uniprot.org/uniprot/Q8BKJ9 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sirtuin family. Class IV subfamily.|||Binds 1 zinc ion per subunit.|||Chromosome|||Cytoplasm|||Detected in liver, spleen and testis (PubMed:16618798). Detected in embryos (PubMed:16618798).|||Interacts with UBTF and the RNA polymerase I complex (By similarity). Interacts with components of the B-WICH complex, such as MYBBP1A, SMARCA5/SNF2H and BAZ1B/WSTF (By similarity). Interacts with ELK4, leading to stabilization at target promoters for H3K18Ac deacetylation (By similarity). Interacts with histone H2A and/or histone H2B (By similarity). Interacts with DNMT1 (PubMed:28842251). Interacts with SIRT1 (PubMed:28842251, PubMed:28923965).|||Methylation at Arg-390 by PRMT6 inhibits the H3K18Ac histone deacetylase activity, promoting mitochondria biogenesis and maintaining mitochondria respiration.|||Mice show a reduction in lifespan and develop heart hypertrophy (PubMed:18239138). The mean and maximum lifespan is reduced by 59% and 55% (PubMed:18239138). Mice develop kyphosis and lose subcutaneous fat early in life; they also show a general decrease in stress-resistance mechanisms (PubMed:18239138). Mice suffer from degenerative heart hypertrophy and inflammatory cardiomyopathy (PubMed:18239138). Hearts are also characterized by an extensive fibrosis (PubMed:18239138). Mice also display multisystemic mitochondrial dysfunction, characterized by increased blood lactate levels, reduced exercise performance, cardiac dysfunction, hepatic microvesicular steatosis and age-related hearing loss (PubMed:25200183). Cells show impaired oxidative phosphorylation (OxPhos) (PubMed:25200183). A substantial proportion of mice also show perinatal lethality and an accelerated aging phenotype, probably caused by increased replication stress and impaired DNA caused repair (PubMed:27225932). Females display reduced fertility and produce fewer oocytes and ovulate fewer eggs (PubMed:31256246). Oocytes show impaired meiotic progression with reduced levels of crossovers and chromosome synapsis defects (PubMed:31256246). Mice also show severe osteopenia characterized by decreased bone formation and an increase of osteoclasts (PubMed:30026585).|||NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids. Histone deacetylase activity is activated by DNA. Protein-lysine deacylase activity is activated by RNA. H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-390. H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7.|||NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase and deglutarylase), depending on the context (PubMed:25200183, PubMed:30026585, PubMed:31075303). Also acts as a dedecanoylase (By similarity). Specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac) (By similarity). In contrast to other histone deacetylases, displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression (By similarity). H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors; SIRT7 thereby acts as a transcription repressor (By similarity). Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells (By similarity). Also able to mediate deacetylation of histone H3 at 'Lys-36' (H3K36Ac) in the context of nucleosomes (By similarity). Also mediates deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1, FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53 (By similarity). Enriched in nucleolus where it stimulates transcription activity of the RNA polymerase I complex (PubMed:16618798). Acts by mediating the deacetylation of the RNA polymerase I subunit POLR1E/PAF53, thereby promoting the association of RNA polymerase I with the rDNA promoter region and coding region (By similarity). In response to metabolic stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased RNA polymerase I transcription (By similarity). Required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis (PubMed:16618798). Promotes pre-ribosomal RNA (pre-rRNA) cleavage at the 5'-terminal processing site by mediating deacetylation of RRP9/U3-55K, a core subunit of the U3 snoRNP complex (By similarity). Mediates 'Lys-37' deacetylation of Ran, thereby regulating the nuclear export of NF-kappa-B subunit RELA/p65 (PubMed:31075303). Acts as a regulator of DNA damage repair by mediating deacetylation of ATM during the late stages of DNA damage response, promoting ATM dephosphorylation and deactivation (By similarity). May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation (PubMed:18239138). Suppresses the activity of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes by mediating deacetylation of DDB1, which prevents the interaction between DDB1 and CUL4 (CUL4A or CUL4B) (By similarity). Activates RNA polymerase II transcription by mediating deacetylation of CDK9, thereby promoting 'Ser-2' phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (By similarity). Deacetylates FBL, promoting histone-glutamine methyltransferase activity of FBL (By similarity). Acts as a regulator of mitochondrial function by catalyzing deacetylation of GABPB1 (PubMed:25200183). Regulates Akt/AKT1 activity by mediating deacetylation of FKBP5/FKBP51 (By similarity). Required to prevent R-loop-associated DNA damage and transcription-associated genomic instability by mediating deacetylation and subsequent activation of DDX21, thereby overcoming R-loop-mediated stalling of RNA polymerases (By similarity). In addition to protein deacetylase activity, also acts as protein-lysine deacylase (By similarity). Acts as a protein depropionylase by mediating depropionylation of Osterix (SP7), thereby regulating bone formation by osteoblasts (PubMed:30026585). Acts as a histone deglutarylase by mediating deglutarylation of histone H4 on 'Lys-91' (H4K91glu); a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (By similarity). Acts as a histone desuccinylase: in response to DNA damage, recruited to DNA double-strand breaks (DSBs) and catalyzes desuccinylation of histone H3 on 'Lys-122' (H3K122succ), thereby promoting chromatin condensation and DSB repair (By similarity). Also promotes DSB repair by promoting H3K18Ac deacetylation, regulating non-homologous end joining (NHEJ) (PubMed:27225932). Along with its role in DNA repair, required for chromosome synapsis during prophase I of female meiosis by catalyzing H3K18Ac deacetylation (PubMed:31256246). Involved in transcriptional repression of LINE-1 retrotransposon via H3K18Ac deacetylation, and promotes their association with the nuclear lamina (PubMed:31226208). Required to stabilize ribosomal DNA (rDNA) heterochromatin and prevent cellular senescence induced by rDNA instability (PubMed:28842251). Acts as a negative regulator of SIRT1 by preventing autodeacetylation of SIRT1, restricting SIRT1 deacetylase activity (PubMed:28923965).|||Phosphorylated during mitosis.|||Ubiquitinated via 'Lys-63'-linked ubiquitin chains. Deubiquitinated by USP7, inhibiting the H3K18Ac histone deacetylase activity and regulating gluconeogenesis. Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to proteasomal degradation.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:H2-Q10 ^@ http://purl.uniprot.org/uniprot/P01898 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MHC class I family.|||Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin).|||Involved in the presentation of foreign antigens to the immune system.|||Membrane http://togogenome.org/gene/10090:Epm2a ^@ http://purl.uniprot.org/uniprot/Q9WUA5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family.|||Cell membrane|||Cytoplasm|||Detected in skeletal muscle and in brain (at protein level) (PubMed:24430976). Widely expressed. Higher levels of expression are found in heart, brain, liver, skeletal muscle and kidney (PubMed:10092504).|||Endoplasmic reticulum membrane|||Homodimer (PubMed:16971387). Interacts with PPP1R3B, PPP1R3C, HIRIP5, and EPM2AIP1 (By similarity). Binds glycogen and Lafora bodies. Interacts with NHLRC1/malin (via the NHL repeats) (By similarity). Forms a complex with NHLRC1/malin and HSP70 (PubMed:19036738). Interacts with PPP1R3D; in the presence of NHLC1/malin the interaction leads to ubiquitination and autophagic degradation of PPP1R3D (PubMed:23624058). Interacts (via the phosphatase domain) with MAPT/Tau; the interaction dephosphorylates MAPT (PubMed:19542233). Interacts with PRDM8 (By similarity).|||Impaired behavioral responses, ataxia, spontaneous myoclonic seizures and progressive accumulation of poorly-branched, insoluble forms of glycogen (Lafora bodies) in liver, brain and skeletal muscle tissue (PubMed:12019206, PubMed:18040046, PubMed:24430976). Expression of both wild-type Epm2a and mutated Epm2a without phosphatase activity can abolish the appearance of Lafora bodies in brain and heart from 7 to over 12 month old mutant mice (PubMed:24430976). At 3 months of age, overall glycogen levels are normal; by 9 months of age, a 3-fold increase in overall glycogen levels and a 6-fold increase in glycogen phosphate levels is observed (PubMed:18040046, PubMed:18852261, PubMed:22669944, PubMed:23663739). Muscle glycogen has an altered structure, with a reduced size, an abnormally high proportion of very short side chains, fewer medium-length chains and an increased number of long chains (PubMed:23663739). Glycogen synthase (Gys1) and 1,4-alpha-glucan-branching enzyme (Gbe1) activities in brain and muscle tissue are normal (PubMed:18040046). 10 month old mice have neurofibrillary tangles (NFTs, aggregates of hyperphosphorylated Mapt/Tau) in brain and muscle tissue, however NFTs are not observed in 4 and 6 month old mice (PubMed:19542233). 3- and 12- month old mice show reduced numbers of autophagosomes in liver extracts, and 3-month old starved mice have increased levels of the autophagy dysfunction marker Map1lc3b/LC3-II and increased levels of ubiquitinated proteins, suggesting impaired macroautophagy (PubMed:20453062).|||In the embryo, highly expressed at 17 dpc. Detected in all postnatal stages, but highest expression is found at day 160 after birth.|||Phosphorylation on Ser-25 by AMPK affects the phosphatase activity of the enzyme and its ability to homodimerize and interact with NHLRC1, PPP1R3C or PRKAA2.|||Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin (PubMed:18040046, PubMed:18852261, PubMed:19036738, PubMed:23663739, PubMed:24430976, PubMed:24068615). Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro) (PubMed:16971387, PubMed:24430976). Has also been shown to dephosphorylate MAPT (PubMed:19542233). Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates (PubMed:18040046, PubMed:18852261, PubMed:23663739). Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS) (PubMed:19036738, PubMed:24068615). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin. Also promotes proteasome-independent protein degradation through the macroautophagy pathway (PubMed:20453062).|||Polyubiquitinated by NHLRC1/malin.|||The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies. http://togogenome.org/gene/10090:Vmn2r28 ^@ http://purl.uniprot.org/uniprot/L7N203 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Rheb ^@ http://purl.uniprot.org/uniprot/Q921J2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alternates between an inactive form bound to GDP and an active form bound to GTP (PubMed:24648513). Inactivated by the TSC-TBC complex via the GTPase activating protein (GAP) domain of TSC2 (PubMed:12820960). Autoinhibited by Tyr-35, which constrains the active site conformation, restricting the access of the catalytic Asp-65 to the nucleotide-binding pocket (By similarity).|||Associates with the mTORC1 complex (MTOR, MLST8 and RPTOR) in a guanyl nucleotide-independent manner (By similarity). Interacts with TSC2 (By similarity). Interacts (when prenylated) with PDE6D; this promotes release from membranes (By similarity).|||Belongs to the small GTPase superfamily. Rheb family.|||Embryonic lethality around midgestation (PubMed:21321084). The inner cell mass differentiates normally, but embryos do not develop beyond 12 dpc embryos, due to impaired development of the cardiovascular system (PubMed:21321084).|||Endomembrane system|||Endoplasmic reticulum membrane|||Farnesylation is important for efficiently activating mTORC1-mediated signaling.|||Golgi apparatus membrane|||Lysosome membrane|||Phosphorylation by MAPKAPK5 impairs GTP-binding and inactivation.|||Polyubiquitinated in response to amino acid, promoting its interaction with MTOR and mTORC1 activation. Deubiquitination by ATXN3 promotes recruitment of the TSC-TBC complex and RHEB inactivation by TSC2. Monoubiquitinated at Lys-8 by RNF152, promoting its association with the TSC-TBC complex. Deubiquitinated at Lys-8 by USP4, promoting mTORC1 activation.|||Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12820960, PubMed:16631613, PubMed:21321084, PubMed:24648513). In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (By similarity). RHEB is also required for localization of the TSC-TBC complex to lysosomal membranes (By similarity). In response to starvation, RHEB is inactivated by the TSC-TBC complex, preventing activation of mTORC1 (By similarity). Has low intrinsic GTPase activity (By similarity).|||The conserved catalytic Gln-64 found in other Ras-like GTPases seems not to be involved in GTP hydrolysis in RHEB.|||cytosol http://togogenome.org/gene/10090:Snca ^@ http://purl.uniprot.org/uniprot/O55042 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.|||Belongs to the synuclein family.|||Cytoplasm|||Expressed in brain (at protein level) (PubMed:31034892). Expressed in the striatum (at protein level) (PubMed:17296554). Highly expressed in presynaptic terminals in the central nervous system (PubMed:10707987).|||Membrane|||Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (By similarity). Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (By similarity). Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (By similarity). Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282, PubMed:25246573). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (By similarity). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (By similarity).|||Nucleus|||Phosphorylated, predominantly on serine residues. Phosphorylated on Tyr-125 upon osmotic stress.|||Secreted|||Snca-deficient mice are viable and fertile, possess intact brain architecture but exhibit decreased striatal dopamin content and amphetamine sensitivity (PubMed:10707987). Simultaneous knockout of SNCA, SNCB and SNCG exhibit an age-dependent decrease in SNARE-complex assembly. Thus, synucleins are required for maintaining normal SNARE-complex assembly during aging in mice (PubMed:20798282).|||Soluble monomer. Homotetramer. A dynamic intracellular population of tetramers and monomers coexists normally and the tetramer plays an essential role in maintaining homeostasis (By similarity). Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones. Interacts (via N-terminus) with synphilin-1/SNCAIP; this interaction promotes formation of SNCA inclusions in the cytoplasm. Interacts with CALM1. Interacts with STXBP1; this interaction controls SNCA self-replicating aggregation. Interacts with SNARE components VAMP2 and SNAP25; these interactions allows SNARE complex assembly and integrity (PubMed:20798282, PubMed:25246573). Interacts with RPH3A and RAB3A (By similarity). Interacts with SERF1A; this interaction promotes the aggregation of SNCA (By similarity). Interacts with SEPTIN4 (PubMed:17296554).|||Synapse|||Ubiquitinated. The predominant conjugate is the diubiquitinated form.|||axon http://togogenome.org/gene/10090:Elmo2 ^@ http://purl.uniprot.org/uniprot/Q8BHL5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts directly with the SH3-domain of DOCK1 via its SH3-binding site (PubMed:25533347). Probably forms a heterotrimeric complex with DOCK1 and RAC1. Interacts with ARHGEF16, DOCK4 and EPHA2; mediates activation of RAC1 by EPHA2 (By similarity). Interacts with ADGRB3 (By similarity). Interacts with AUTS2; the interaction is direct (PubMed:25533347).|||Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1 (By similarity).|||Membrane|||cytosol http://togogenome.org/gene/10090:Rexo1 ^@ http://purl.uniprot.org/uniprot/Q7TT28 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the REXO1/REXO3 family.|||Interacts with TCEA2 and ELOA.|||May be due to an intron retention.|||Nucleus|||Seems to have no detectable effect on transcription elongation in vitro. http://togogenome.org/gene/10090:Nedd8 ^@ http://purl.uniprot.org/uniprot/P29595|||http://purl.uniprot.org/uniprot/Q3UI46 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:1378265 and PubMed:15183309, down-regulated during embryonic development, but according to PubMed:10597293, expression does not change during embryonic development. Between 10 dpc and 12 dpc, expressed in heart and spinal ganglia. Between 13.5 dpc and 16.5 dpc, strongly expressed in spinal and sympathetic ganglia, neural epithelium of the retina, oral and olfactory epithelia and thymus.|||Belongs to the ubiquitin family.|||Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.|||Interacts with AHR; interaction is direct. Interacts with NUB1; interaction is direct.|||Mice die in utero at the periimplantation stage due to impaired cell cycle progression (PubMed:11696557). Embryos show selective apoptosis of the inner cell mass but not of trophoblastic cells (PubMed:11696557). However, trophoblastic cells do not enter the S phase of the endoreduplication cycle (PubMed:11696557).|||Nucleus|||Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53 (PubMed:11696557). Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M (By similarity).|||Ubiquitously expressed (at protein level). http://togogenome.org/gene/10090:Xlr3c ^@ http://purl.uniprot.org/uniprot/B1B0S0 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Hoxd10 ^@ http://purl.uniprot.org/uniprot/P28359 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Expressed in the developing limb buds. Expressed in the posterior-most regions of the fetus. Strongly expressed in 12.5 day old fetuses in both spinal cord and pre-vertebral column with an anterior boundary of expression lying at the level of the second or third lumbar pre-vertebrae.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Hecw2 ^@ http://purl.uniprot.org/uniprot/Q6I6G8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73. Involved in the regulation of mitotic metaphase/anaphase transition.|||Interacts with TP73 (By similarity). Interacts with FZR1 (By similarity).|||spindle http://togogenome.org/gene/10090:Tsc22d2 ^@ http://purl.uniprot.org/uniprot/E9Q7M2|||http://purl.uniprot.org/uniprot/Q9CVK3 ^@ Function|||Induction|||Sequence Caution|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TSC-22/Dip/Bun family.|||Expressed in the cortex, medulla and papilla of the kidney.|||Expressed in the kidney.|||Induced by renal hypertonic stress, via mRNA stabilization.|||Interacts with NRBP1 (By similarity). Interacts with PKM isoform M2; the interaction results in reduced nuclear levels of PKM isoform M2, leading to repression of cyclin CCND1 transcription and reduced cell growth (By similarity). Interacts with WDR77 (By similarity).|||May protect kidney cells from hyperosmotic stress.|||Probable cloning artifact.|||Reduces the level of nuclear PKM isoform M2 which results in repression of cyclin CCND1 transcription and reduced cell growth. http://togogenome.org/gene/10090:Fbxl22 ^@ http://purl.uniprot.org/uniprot/Q8C7B6 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Directly interacts with SKP1 and CUL1.|||Enriched in cardiac muscle (at protein level).|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes ubiquitination of sarcomeric proteins alpha-actinin-2 (ACTN2) and filamin-C (FLNC) (By similarity).|||Z line http://togogenome.org/gene/10090:Habp4 ^@ http://purl.uniprot.org/uniprot/E9QKB2|||http://purl.uniprot.org/uniprot/Q3UJC1|||http://purl.uniprot.org/uniprot/Q9JKS5 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with ribosomes; promoting ribosome stabilization (By similarity). Interacts with EEF2/eEF2; promoting ribosome stabilization (By similarity). Interacts with FMR1. Interacts with FXR1 and FXR2. Interacts with CHD3 (via C-terminus). Interacts (via C-terminus) with RACK1. Interacts with p53/TP53 (By similarity). Interacts (via N-terminus) with SRSF9; this interaction is direct (PubMed:19523114). Interacts with SYNCRIP; this interaction is direct. Interacts with MEF2C (via N-terminus); this interaction decreases DNA-binding activity of MEF2C in myocardial cells in response to mechanical stress. Interacts with PRMT1 (via N-terminus) (By similarity). Interacts with SPIN1 (PubMed:23894536).|||Belongs to the SERBP1-HABP4 family.|||Cajal body|||Cytoplasm|||Expressed in adult heart, brain, liver, kidney, testis, and in various embryonic tissues, but not in adult spleen, lung or skeletal muscle.|||Intron retention.|||Methylated. Methylation is decreased by phorbol 12-myristate 13-acetate (PMA)-activated PKC, in vitro.|||Nucleus|||Nucleus speckle|||Phosphorylated by phorbol 12-myristate 13-acetate (PMA)-activated PKC isoforms at Thr-352 and Thr-373.|||Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (By similarity). Acts via its association with EEF2/eEF2 factor at the A-site of the ribosome, promoting ribosome stabilization in an inactive state compatible with storage (By similarity). Plays a key role in ribosome hibernation in the mature oocyte by promoting ribosome stabilization (By similarity). Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo (By similarity). Also binds RNA, regulating transcription and pre-mRNA splicing. Binds (via C-terminus) to poly(U) RNA. Seems to play a role in PML-nuclear bodies formation (By similarity). Negatively regulates DNA-binding activity of the transcription factor MEF2C in myocardial cells in response to mechanical stress (By similarity).|||Stress granule|||The C-terminal region is necessary for nucleus and cytoplasmic localization. The N-terminal region is necessary for nucleus and nuclear bodies localization. Regions containing Arg-Gly-Gly repeats (RGG/RXR-box) may be preferentially methylated by PRMT1.|||gem|||nuclear body|||nucleolus|||sarcoplasm http://togogenome.org/gene/10090:Tinag ^@ http://purl.uniprot.org/uniprot/Q9WUR0 ^@ Similarity ^@ Belongs to the peptidase C1 family. http://togogenome.org/gene/10090:Gdf10 ^@ http://purl.uniprot.org/uniprot/P97737|||http://purl.uniprot.org/uniprot/Q8C991 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 3T3-L1 cells endogenously secrete biologically active Gdf10 as a unique complex that contains both the pro-region and the mature region.|||Belongs to the TGF-beta family.|||During embryogenes is expressed most prominently in developing skeletal structures both in the craniofacial region and in the vertebral column.|||Growth factor involved in osteogenesis and adipogenesis. Plays an inhibitory role in the process of osteoblast differentiation via SMAD2/3 pathway (PubMed:22155034). Plays an inhibitory role in the process of adipogenesis (PubMed:21712809).|||Highly expressed in epididymal adipose tissue, brain, bone and aorta and to a lesser extent in liver and spleen. Expressed at higher levels in preadipocytes than in mature adipocytes (PubMed:21712809). Strongly expressed in glial cells of the cerebellum (PubMed:24963847).|||Homodimer or heterodimer. Can form a non-covalent complex of the mature region and the pro-region (PubMed:21712809).|||No visible phenotype.|||Secreted http://togogenome.org/gene/10090:Nudt14 ^@ http://purl.uniprot.org/uniprot/Q9D142 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Nudix hydrolase family.|||Cytoplasm|||Homodimer.|||Hydrolyzes UDP-glucose to glucose 1-phosphate and UMP and ADP-ribose to ribose 5-phosphate and AMP. The physiological substrate is probably UDP-glucose. Poor activity on other substrates such as ADP-glucose, CDP-glucose, GDP-glucose and GDP-mannose (By similarity). http://togogenome.org/gene/10090:Tnfsf13 ^@ http://purl.uniprot.org/uniprot/Q5F2A4|||http://purl.uniprot.org/uniprot/Q9D777 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cytokine that binds to TNFRSF13B/TACI and to TNFRSF17/BCMA. Plays a role in the regulation of tumor cell growth. May be involved in monocyte/macrophage-mediated immunological processes.|||Homotrimer.|||Secreted|||The soluble form derives from the membrane form by proteolytic processing.|||Transgenic mice develop lymphoid tumors that originate from expansion of the peritoneal B-1 B-cell population. Aging transgenic mice develop progressive hyperplasia in mesenteric lymph nodes and Peyer patches, disorganization of affected lymphoid tissues, mucosal and capsular infiltration, and eventual tumor cell infiltration into non-lymphoid tissues such as kidney and liver (PubMed:15488762). http://togogenome.org/gene/10090:Fshr ^@ http://purl.uniprot.org/uniprot/B2RQM3|||http://purl.uniprot.org/uniprot/P35378 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.|||Cell membrane|||G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.|||Homotrimer. Functions as a homotrimer binding the FSH hormone heterodimer composed of CGA and FSHB (By similarity). Interacts with ARRB2 (By similarity). Interacts with APPL2; interaction is independent of follicle stimulating hormone stimulation (By similarity).|||Membrane|||N-glycosylated; indirectly required for FSH-binding, possibly via a conformational change that allows high affinity binding of hormone.|||Sulfated. http://togogenome.org/gene/10090:Cystm1 ^@ http://purl.uniprot.org/uniprot/D3YWV2 ^@ Similarity ^@ Belongs to the CYSTM1 family. http://togogenome.org/gene/10090:Harbi1 ^@ http://purl.uniprot.org/uniprot/Q8BR93 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HARBI1 family.|||Cytoplasm|||Detected in adult brain, eye, nerve tissue and lung. Detected in embryo.|||Interacts with NAIF1.|||Nucleus|||Transposase-derived protein that may have nuclease activity (Potential). Does not have transposase activity (By similarity). http://togogenome.org/gene/10090:Zfp2 ^@ http://purl.uniprot.org/uniprot/P08043 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Probable transcription factor involved in neuronal differentiation and/or phenotypic maintenance. http://togogenome.org/gene/10090:Lrsam1 ^@ http://purl.uniprot.org/uniprot/Q80ZI6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (viral proteins) cargos (By similarity). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (By similarity). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (By similarity).|||Interacts with TSG101. Interacts with PHF23. Interacts with FUS.|||The LRR domain is necessary and sufficient for localization to bacterial targets.|||The PTAP motifs mediate the binding to UEV domains.|||The RING domain is required for ubiquitination.|||The coiled coil domains interact with the SB domain of TSG101.|||Ubiquitination promoted by PHF23 leads to proteasomal degradation.|||Widely expressed. http://togogenome.org/gene/10090:Lingo2 ^@ http://purl.uniprot.org/uniprot/Q3URE9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Sost ^@ http://purl.uniprot.org/uniprot/Q99P68 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sclerostin family.|||Interacts with LRP4 (via the extracellular domain); the interaction facilitates the inhibition of Wnt signaling. Interacts with LRP5 (via the first two YWTD-EGF repeat domains); the interaction inhibits Wnt-mediated signaling. Interacts with LRP6.|||Mice were resistant to mechanical unloading-induced bone loss.|||Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.|||extracellular matrix http://togogenome.org/gene/10090:Rbm12 ^@ http://purl.uniprot.org/uniprot/Q8R4X3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Hic2 ^@ http://purl.uniprot.org/uniprot/Q9JLZ6 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family. Hic subfamily.|||Nucleus|||Probable cloning artifact.|||Self-associates. Interacts with HIC1 (By similarity).|||Transcriptional repressor. http://togogenome.org/gene/10090:Or51a8 ^@ http://purl.uniprot.org/uniprot/Q8VH12 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ube2e3 ^@ http://purl.uniprot.org/uniprot/P52483 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination (By similarity). Participates in the regulation of transepithelial sodium transport in renal cells. May be involved in cell growth arrest.|||Belongs to the ubiquitin-conjugating enzyme family.|||Cytoplasm|||Interacts with NEDD4L. The ubiquitin-loaded form interacts specifically with importin-11 (IPO11), leading to its import into the nucleus.|||Nucleus http://togogenome.org/gene/10090:Pitpnm1 ^@ http://purl.uniprot.org/uniprot/O35954 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.|||Catalyzes the transfer of phosphatidylinositol (PI) between membranes (By similarity). Binds PI (PubMed:10400687). Also binds phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC (By similarity). Regulates RHOA activity, and plays a role in cytoskeleton remodeling (By similarity). Necessary for normal completion of cytokinesis (By similarity). Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus (By similarity). Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus (By similarity). Required for protein export from the endoplasmic reticulum and the Golgi (By similarity). Binds calcium ions (By similarity).|||Cleavage furrow|||Cytoplasm|||Detected at high levels in brain, and at lower levels in lung, kidney, spleen and liver (at protein level). Ubiquitous. Highly expressed in embryonic retina and the central nervous system.|||Detected at low levels during fetal development up to day 15. Highly expressed at day 17.|||Endoplasmic reticulum membrane|||Golgi stack membrane|||Interacts with PTK2B via its C-terminus. Interacts with RHOA. Has higher affinity for the inactive, GDP-bound form of RHOA. The CDK1-phosphorylated form interacts with PLK1. Interacts with VAPB and PIK4CA (By similarity).|||Lipid droplet|||Midbody|||Phosphorylated on multiple sites by CDK1 at the onset of mitosis. Phosphorylation facilitates dissociation from the Golgi complex and is required for interaction with PLK1 (By similarity).|||Phosphorylated on threonine residues upon treatment with oleic acid.|||Phosphorylated on tyrosine residues by PTK2B. http://togogenome.org/gene/10090:Pax4 ^@ http://purl.uniprot.org/uniprot/A2RRY5|||http://purl.uniprot.org/uniprot/B7ZNC8|||http://purl.uniprot.org/uniprot/P32115 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the paired homeobox family.|||Expressed in early pancreas. Later restricted to beta cells. Undetectable in adult islets.|||Nucleus|||Plays an important role in the differentiation and development of pancreatic islet beta cells. Transcriptional repressor that competes with PAX6 in binding to a common element in the glucagon, insulin and somatostatin promoters. http://togogenome.org/gene/10090:Sox1 ^@ http://purl.uniprot.org/uniprot/P53783 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Mainly in the developing central nervous system. Expressed in developing urogenital ridge.|||Nucleus|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional activator. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity). http://togogenome.org/gene/10090:Prom1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JDH9|||http://purl.uniprot.org/uniprot/A0A0G2JE50|||http://purl.uniprot.org/uniprot/A0A0R4J0B0|||http://purl.uniprot.org/uniprot/G3X9J8|||http://purl.uniprot.org/uniprot/G5E8G5|||http://purl.uniprot.org/uniprot/O54990|||http://purl.uniprot.org/uniprot/Q8CDK8|||http://purl.uniprot.org/uniprot/Q8R056 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-226, Lys-258 and Lys-265 by NAT8 and NAT8B may control PROM1 protein expression and its function in cell apoptosis.|||Apical cell membrane|||At birth, is detected at the interface between the developing neuroretina and the retinal pigment epithelium (RPE) layer. In the postnatal retina (P20) detected in photoreceptors, with particular concentration in the region of plasma membrane evaginations at the basal part of the outer segment (OS). Expressed by rod and cone photoreceptor cells, most abundantly between the OS and inner segment (IS), in close proximity to the connecting cilium.|||Belongs to the prominin family.|||Endoplasmic reticulum|||Endoplasmic reticulum-Golgi intermediate compartment|||Fundus images and light microscopy of retinal sections from transgenic mice expressing mutant PROM1 reveal progressive retinal abnormalities visible as subretinal deposits and photoreceptor atrophy.|||In the submandibular gland, expressed on the apical side of epithelial cells. In the parotid gland, expressed in the intercalated ducts. In the sublingual gland, expressed in intercalated ducts. In the extraorbital lacrimal gland, expressed in the intercalated tubules and larger intralobular ducts. Expressed in the retina. Present in urine within small membrane particles (at protein level). In the embryo, expressed on the apical side of neuroepithelial cells and of other epithelia such as lung buds, gut and ureter buds. In the adult, expressed at the apical side of the kidney tubules and of the ependymal layer of the brain. Not expressed in gut, liver, lung, pituitary, adrenal, heart or spleen. Localized to the nascent disk membranes at the base of the rod outer segment in the retina (at protein level).|||Interacts with CDHR1 and with actin filaments. Interacts with NAT8 and NAT8B (By similarity).|||May play a role in cell differentiation, proliferation and apoptosis. Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization of the apical plasma membrane in epithelial cells. During early retinal development acts as a key regulator of disk morphogenesis (PubMed:19228982). Involved in regulation of MAPK and Akt signaling pathways. In neuroblastoma cells suppresses cell differentiation such as neurite outgrowth in a RET-dependent manner.|||Membrane|||Progressive degeneration and functional deterioration of both cone and rod photoreceptors associated with impaired morphogenesis of the disks and OS.|||microvillus membrane|||photoreceptor outer segment http://togogenome.org/gene/10090:Dmrt1 ^@ http://purl.uniprot.org/uniprot/Q9QZ59 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DMRT family.|||Detected already at 9.5 dpc. At 10.5 dpc, expressed in the genital ridges of both sexes. At 14.5 dpc, during gonadal sexual differentiation, expression declines in the ovary, but is maintained in the testis, where it becomes restricted to Sertoli and germ cells in the developing seminiferous tubules of the testis. Accumulates primarily in Sertoli cells. From P1, appears in germ cells and reach high levels by P7, just before meiosis begins. From P7 through adult stage, present in Sertoli cells and undifferentiated germ cells, but not in differentiating germ cells.|||Nucleus|||Severe defects in the adult testis with hypoplastic testes and disorganization of seminiferous tubules and absence of germ cells, due to pre-meiotic germ cell death in testes. Sertoli cell fail to differentiate. Female mutant mice have normal ovaries and are fertile. Depending on the strain background mice also show testis teratomas: deletion in 129/Sv strain causes a high incidence of teratomas, whereas these tumors do not form in C57BL/6J mutant mice. Deletion of Dmrt1 during fetal development causes postnatal Sertoli cells to lose male-promoting Sox9 and instead activation of female-promoting genes such as Foxl2, leading to reprogrammation of Sertoli cells into granulosa cells. As a consequence, theca cells form, estrogen is produced and germ cells appear feminized.|||Testis-specific. In adult testis, expressed in Sertoli cells in all regions of the seminiferous tubules. Expressed dynamically in premeiotic germ cells (spermatogonia), with high expression only in regions of the seminiferous tubule that are early in the spermatogenic cycle (at protein level). Expressed in all mitotic spermatogonia. Expression decreases with the onset of spermatogonial differentiation and disappears at the initiation of meiosis.|||Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. Plays a central role in spermatogonia by inhibiting meiosis in undifferentiated spermatogonia and promoting mitosis, leading to spermatogonial development and allowing abundant and continuous production of sperm. Acts both as a transcription repressor and activator: prevents meiosis by restricting retinoic acid (RA)-dependent transcription and repressing STRA8 expression and promotes spermatogonial development by activating spermatogonial differentiation genes, such as SOHLH1. Also plays a key role in postnatal sex maintenance by maintaining testis determination and preventing feminization: represses transcription of female promoting genes such as FOXL2 and activates male-specific genes. May act as a tumor suppressor. May also play a minor role in oogenesis. http://togogenome.org/gene/10090:Nptx2 ^@ http://purl.uniprot.org/uniprot/O70340|||http://purl.uniprot.org/uniprot/Q3UYB9 ^@ Caution|||Cofactor|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds 2 calcium ions per subunit.|||Homooligomer or heterooligomer (probably pentamer) with neuronal pentraxin receptor (NPTXR).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Likely to play role in the modification of cellular properties that underlie long-term plasticity. Binds to agar matrix in a calcium-dependent manner (By similarity).|||Secreted http://togogenome.org/gene/10090:Crot ^@ http://purl.uniprot.org/uniprot/Q9DC50 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the carnitine/choline acetyltransferase family.|||Beta-oxidation of fatty acids. The highest activity concerns the C6 to C10 chain length substrate.|||Peroxisome http://togogenome.org/gene/10090:Uck1 ^@ http://purl.uniprot.org/uniprot/A2AN37|||http://purl.uniprot.org/uniprot/P52623 ^@ Function|||Similarity ^@ Belongs to the uridine kinase family.|||Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate (PubMed:8951040). Does not phosphorylate deoxyribonucleosides or purine ribonucleosides. Can use ATP or GTP as a phosphate donor (By similarity). http://togogenome.org/gene/10090:Rab37 ^@ http://purl.uniprot.org/uniprot/Q9JKM7 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasmic vesicle|||Interacts with RIMS1.|||Specifically expressed in the bone marrow mast cells. http://togogenome.org/gene/10090:Kctd6 ^@ http://purl.uniprot.org/uniprot/Q8BNL5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in cerebellum and brain.|||Homopentamer. Interacts with KCTD11; KCTD6 and KCTD11 may associate in heteropentameric assemblies. Interacts (via BTB domain) with CUL3; initially a 4:4 stoichiometry has been reported, however, electron microscopy revealed pentameric states with a five-pointed pinwheel shape. The interaction with CUL3 is indicative for a participation in a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Interacts with HDAC1; probably indirect as the interaction requires the presence of KCTD11. Interacts with USP21 (preferentially catalytic inactive form). Interacts with ANK1 isoform Mu7; detected in striated muscle. Interacts with USP11 (By similarity).|||M line|||Probable substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes the ubiquitination of HDAC1; the function seems to depend on KCTD11:KCTD6 oligomerization. Can function as antagonist of the Hedgehog pathway by affecting the nuclear transfer of transcription factor GLI1; the function probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. Inhibits cell growth and tumorigenicity of medulloblastoma (MDB). Involved in regulating protein levels of ANK1 isoform Mu7 probably implicating CUL3-dependent proteasomal degradation. http://togogenome.org/gene/10090:Nutm2 ^@ http://purl.uniprot.org/uniprot/Q3V0C3 ^@ Similarity ^@ Belongs to the NUT family. http://togogenome.org/gene/10090:Gab2 ^@ http://purl.uniprot.org/uniprot/Q3ZB57|||http://purl.uniprot.org/uniprot/Q3ZB59 ^@ Similarity ^@ Belongs to the GAB family. http://togogenome.org/gene/10090:Il17re ^@ http://purl.uniprot.org/uniprot/Q8BH06 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Expression starts at 10.5 dpc and reaches a plateau of expression at 12.5 dpc.|||Forms heterodimers with IL17RA; the heterodimer binds IL17C.|||Mutant animals are born normally at the expected Mendelian frequency. They exhibit much lower expression of genes encoding antibacterial molecules, much greater bacterial burdens and total mortality after infection with Citrobacter rodentium.|||Predominantly expressed in mucosal tissues, including trachea, lung, kidney and stomach. Highly expressed in colon epithelial cells. Also expressed in testis. Low expression, if any, in heart, liver, spleen, or brain. Among CD4 T-helper cells, expressed at high levels in Th17 cells.|||Secreted|||Specific functional receptor for IL17C, signaling through the NF-kappa-B and MAPK pathways. Requires TRAF3IP2 /ACT1 for signaling. Crucial regulator in innate immunity to bacterial pathogens, such as Citrobacter rodentium. Isoform 4 and isoform 5 may be either cytoplasmic inactive or dominant active forms. Isoform 2 and isoform 3 may act as soluble decoy receptors.|||Up-regulated by its own ligand IL17C. Also up-regulated by IL6 and TNF acting synergically. This induction can be further increased by IL23. http://togogenome.org/gene/10090:S100a5 ^@ http://purl.uniprot.org/uniprot/P63084|||http://purl.uniprot.org/uniprot/Q149U2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the S-100 family.|||Binds calcium, zinc and copper. One subunit can simultaneously bind 2 calcium ions or 2 copper ions plus 1 zinc ion. Calcium and copper ions compete for the same binding sites (By similarity).|||Homodimer. http://togogenome.org/gene/10090:Timm8a2 ^@ http://purl.uniprot.org/uniprot/Q4FZG7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small Tim family.|||Heterohexamer; possibly composed of 3 copies of TIMM8AB and 3 copies of TIMM13.|||Mitochondrion inner membrane|||Putative mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity).|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of Timm8ab from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). http://togogenome.org/gene/10090:Or9i14 ^@ http://purl.uniprot.org/uniprot/Q8VG65 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Leprot ^@ http://purl.uniprot.org/uniprot/O89013 ^@ Caution|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OB-RGRP/VPS55 family.|||Endosome membrane|||Golgi apparatus membrane|||Interacts with LEPR. Interacts with RAB13 (By similarity).|||May be due to competing acceptor splice site.|||Negatively regulates leptin receptor (LEPR) cell surface expression, and thus decreases response to leptin. Negatively regulates growth hormone (GH) receptor cell surface expression in liver. May play a role in liver resistance to GH during periods of reduced nutrient availability.|||This protein is encoded by the leptin receptor (LEPR) gene, but shares with LEPR only the first two 5'-UTR exons. It therefore does not share any sequence similarity with LEPR.|||Up-regulated in the liver of fasting animals.|||Widely distributed in the brain, with elevated expression in the hypothalamic regions, including the paraventricular nucleus. In the placenta, present at high levels in the junctional zone situated towards the maternal aspect and throughout the labyrinth zone in close proximity to the developing fetus. http://togogenome.org/gene/10090:Gclm ^@ http://purl.uniprot.org/uniprot/O09172|||http://purl.uniprot.org/uniprot/Q4FJZ6 ^@ Similarity|||Subunit ^@ Belongs to the aldo/keto reductase family. Glutamate--cysteine ligase light chain subfamily.|||Heterodimer of a catalytic heavy chain and a regulatory light chain. http://togogenome.org/gene/10090:Kcnb1 ^@ http://purl.uniprot.org/uniprot/Q03717 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated. Acetylation occurs in pancreatic beta cells in response to stimulation by incretin hormones in a histone acetyltransferase (HAT)/histone deacetylase (HDAC)-dependent signaling pathway, promoting beta cell survival.|||Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.|||Cell membrane|||Expressed in the brain (PubMed:17767909, PubMed:22056818). Expressed in the heart (PubMed:14684365). Expressed in pyramidal neurons and interneurons of the hippocampus (PubMed:22056818, PubMed:24494598). Expressed in neocortical pyramidal neurons (PubMed:22056818, PubMed:24477962). Expressed in dorsal root ganglia (DRG) neurons (PubMed:19357235). Expressed in pancreatic beta cells (PubMed:12270920, PubMed:17767909). Expressed in Schwann cells (PubMed:10921884). Expressed in ventricular myocytes (at protein level) (PubMed:14684365, PubMed:10506487).|||Homotetramer or heterotetramer with KCNB2. Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (By similarity). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (PubMed:22056818). Interacts with KCNV2 (By similarity). Self-associates (via N-terminus and C-terminus); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel. Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons. Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner. Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate. Interacts with CREB1; this promotes channel acetylation in response to stimulation by incretin hormones. Interacts (via N-terminus and C-terminus) with MYL12B. Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface. Interacts with SUMO1 (By similarity). Interacts (via phosphorylated form) with PTPRE isoform 2; this reduces phosphorylation and channel activity in heterologous cells (PubMed:10921884). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).|||Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata. Inhibited by 100 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (By similarity). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:2002364, PubMed:10414301, PubMed:15858231). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).|||Lateral cell membrane|||Membrane|||Mice show normal motor coordination and visual acuity, but are hyperactive, exhibit defects in spatial learning ability and show reduced anxiety-like behavior (PubMed:24494598). Show a higher incidence and a shorter latency to seizure progression compared to wild-type mice (PubMed:24494598). Display reduced fasting blood glucose levels and elevated serum insulin levels (PubMed:17767909, PubMed:19383458). Glucose tolerance and insulin secretion is enhanced compared to control animals (PubMed:17767909, PubMed:19383458). Show impaired long-term potentiation in hippocampal neurons (PubMed:24494598). Display a reduction in the slowly deactivating delayed rectifier potassium current in hippocampal pyramidal neurons (PubMed:24494598). Glucose-induced action potential (AP) duration and amplitude is increased while the firing frequency is reduced in pancreatic beta cells (PubMed:17767909, PubMed:19383458).|||Perikaryon|||Phosphorylated. Differential C-terminal phosphorylation on a subset of serines allows graded activity-dependent regulation of channel gating in hippocampal neurons. Ser-607 and Tyr-128 are significant sites of voltage-gated regulation through phosphorylation/dephosphorylation activities. Tyr-128 can be phosphorylated by Src and dephosphorylated by cytoplasmic form of the phosphatase PTPRE. CDK5-induced Ser-607 phosphorylation increases in response to acute blockade of neuronal activity. Phosphorylated on Tyr-128 by Src and on Ser-804 by MAPK14/P38MAPK; phosphorylations are necessary and sufficient for an increase in plasma membrane insertion, apoptotic potassium current surge and completion of the neuronal cell death program. Phosphorylated on Ser-520, Ser-655, Ser-607 and Ser-804 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation. The Ser-607 phosphorylation state differs between KCNB1-containing clusters on the proximal and distal portions of the axon initial segment (AIS). Highly phosphorylated on serine residues in the C-terminal cytoplasmic tail in resting neurons. Phosphorylated in pancreatic beta cells in response to incretin hormones stimulation in a PKA- and RPS6KA5/MSK1-dependent signaling pathway, promoting beta cell survival. Phosphorylation on Ser-567 is reduced during postnatal development with low levels at P2 and P5; levels then increase to reach adult levels by P14. Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-655 and Ser-719 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties. Dephosphorylation by phosphatase PTPRE confers neuroprotection by its inhibitory influence on the neuronal apoptotic potassium current surge in a Zn(2+)-dependent manner. Dephosphorylated at Ser-607 by protein phosphatase PPP1CA. Hypoxia-, seizure- or glutamate-induced neuronal activities promote calcium/calcineurin-dependent dephosphorylation resulting in a loss of KCNB1-containing clustering and enhanced channel activity. In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-719 are less dephosphorylated. In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced (By similarity). Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic nerve tissue (PubMed:10921884). Phosphorylation at Ser-593 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB (By similarity).|||Postsynaptic cell membrane|||Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity. Sumoylation increases the frequency of repetitive action potential firing at the cell surface of hippocampal neurons and decreases its frequency in pancreatic beta cells. Desumoylated by SENP1.|||Synapse|||The FFAT motif is involved in the interaction with VAPA and VAPB and its phosphorylation regulates these interactions.|||The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (By similarity). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits (PubMed:22056818). The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells. The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons (By similarity).|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.|||Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:14684365, PubMed:19383458, PubMed:24494598). Also plays a role in the regulation of exocytosis independently of its electrical function (By similarity). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:22056818). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (By similarity). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits, such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (PubMed:22056818). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle (PubMed:10506487, PubMed:12270920, PubMed:17767909, PubMed:23161216, PubMed:24494598). Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation (By similarity). Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (PubMed:24494598). Contributes to the regulation of the glucose-induced amplitude and duration of action potentials in pancreatic beta-cells, hence limiting calcium influx and insulin secretion (PubMed:12270920, PubMed:17767909, PubMed:19383458, PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells (By similarity). May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (PubMed:10506487, PubMed:14684365). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury (By similarity). May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (By similarity). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity).|||axon|||dendrite|||sarcolemma|||synaptosome http://togogenome.org/gene/10090:Slc49a4 ^@ http://purl.uniprot.org/uniprot/Q8BFQ6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily.|||Cleaved in lysosomes by cathepsin L between Leu-214 and Ala-261, generating a N-glycosylated N-terminal and a non-glycosylated C-terminal fragment.|||Lysosome membrane|||Mediates H(+)-dependent pyridoxine transport. http://togogenome.org/gene/10090:Lce1l ^@ http://purl.uniprot.org/uniprot/Q9D1G7 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Abcc9 ^@ http://purl.uniprot.org/uniprot/E9PUE8|||http://purl.uniprot.org/uniprot/P70170 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.|||Interacts with KCNJ11.|||Isoforms SUR2A and SUR2B are found in cerebellum, eye, atrium, ventricle, urinary bladder and skeletal muscle. Isoform SUR2B is also found in forebrain, liver, lung, pancreas, kidney, spleen, stomach, small intestine, colon, uterus, ovary and fat tissue. Isoform SUR2C is expressed exclusively in the heart.|||Membrane|||Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation. http://togogenome.org/gene/10090:Vmn1r130 ^@ http://purl.uniprot.org/uniprot/D3YTY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Map4k1 ^@ http://purl.uniprot.org/uniprot/P70218 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subunit|||Tissue Specificity ^@ Autophosphorylates: phosphorylation promotes ubiquitination by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Expressed in hemopoietic cells (at protein level) (PubMed:11509653). Ubiquitously expressed in all tissues examined at embryonic stage 16.5 dpc with high levels in lung, heart and fetal liver. In the neonate, expression is restricted to the tissues which undergo lineage decisions, lung, thymus, liver, kidney and brain. In the adult, expression is limited to hemopoietic organs, thymus, bone marrow, and spleen and to the testis (PubMed:9003777).|||Interacts with MAP3K1 (By similarity). Interacts with FBXW8 (By similarity). Interacts with CLNK (via its SH2 domain) (PubMed:11509653).|||Intron retention.|||Serine/threonine-protein kinase, which may play a role in the response to environmental stress (By similarity). Appears to act upstream of the JUN N-terminal pathway (PubMed:9003777). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:9003777). Able to autophosphorylate (PubMed:9003777). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (PubMed:11509653).|||Tyrosine-phosphorylated after activation of hemopoietic cells.|||Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex following autophosphorylation, leading to its degradation by the proteasome. http://togogenome.org/gene/10090:Kcnk7 ^@ http://purl.uniprot.org/uniprot/A0A494B9E8|||http://purl.uniprot.org/uniprot/Q9JJ14|||http://purl.uniprot.org/uniprot/Q9Z2T1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Detected in embryo, eye, lung and liver. Weakly expressed in colon, testis, atria, kidney, intestine, bladder, uterus, ovary, salivary gland, thymus and brain stem. Not detected in brain, cerebellum, spinal cord, heart, ventricle, skeletal muscle, liver, placenta and pancreas. In the eye, highly expressed in the retinal ganglion cell layer and inner nuclear layer.|||Homodimer.|||Membrane|||Probable potassium channel subunit. No channel activity observed in vitro as protein remains in the endoplasmic reticulum. May need to associate with an as yet unknown partner in order to reach the plasma membrane. http://togogenome.org/gene/10090:Ppp2ca ^@ http://purl.uniprot.org/uniprot/P63330 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP phosphatase family. PP-1 subfamily.|||Binds 2 manganese ions per subunit.|||Cytoplasm|||Double mutation Phe-307 and Gln-309 results in association of the PP2A C subunit with alpha-4 protein.|||Nucleus|||PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunitst (By similarity). Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with NXN; the interaction is direct (By similarity). Interacts with KCTD20 (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256). Interacts with SGO1 and SGO2 (By similarity). Interacts with TP53 (By similarity). Interacts with AXIN1; the interaction dephosphorylates AXIN1 (By similarity). Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3 (By similarity). Interacts with RAF1 (By similarity). Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination (By similarity). Interacts with GSK3B (via C2 domain) (By similarity). Interacts with MFHAS1; retains PPP2CA into the cytoplasm and excludes it from the nucleus (By similarity). Interacts with PABIR1/FAM122A (By similarity). Interacts with ADCY8; interaction is phosphatase activity-dependent; antagonizes interaction between ADCY8 and calmodulin (PubMed:16258073). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2; the interaction is inhibited by TESK1 interaction with SPRY2, possibly by vesicular sequestration of SPRY2 (By similarity). Interacts with TRAF3IP3 (By similarity). Interacts with AMBRA1 (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3 (PubMed:25438055). Forms a complex with AMBRA1 and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (By similarity).|||PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (By similarity). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (By similarity). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (PubMed:18084284). Can dephosphorylate p53/TP53 (By similarity). Activates RAF1 by dephosphorylating it at 'Ser-259' (By similarity). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (By similarity). Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (PubMed:25438055). Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (By similarity). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28465465). Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (PubMed:26974206, PubMed:33505023). Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability (PubMed:33505023).|||Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.|||Polyubiquitinated, leading to its degradation by the proteasome (By similarity). May be monoubiquitinated by NOSIP (PubMed:25546391).|||Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (Lcmt1) and protein phosphatase methylesterase 1 (Ppme1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization.|||centromere|||spindle pole http://togogenome.org/gene/10090:Ccser1 ^@ http://purl.uniprot.org/uniprot/Q8C0C4 ^@ Similarity ^@ Belongs to the CCSER family. http://togogenome.org/gene/10090:Sall2 ^@ http://purl.uniprot.org/uniprot/Q9QX96 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sal C2H2-type zinc-finger protein family.|||Expressed throughout embryonic development. In adult predominantly in brain.|||No overt phenotypic abnormalities. Histologic analysis of the eyes reveales a colobomatous phenotype, with delayed apposition of the optic fissure margins and persistence of an anterior retinal coloboma phenotype after birth. Deficient embryos display correct posterior closure toward the optic nerve head, and upon contact of the fissure margins, dissolution of the basal lamina occurs and PAX2, known to be critical for this process, is expressed normally. Anterior closure is disrupted with the fissure margins failing to meet, or in some cases misaligning leading to a retinal lesion.|||Nucleus|||Probable transcription factor that plays a role in eye development before, during, and after optic fissure closure. http://togogenome.org/gene/10090:Cracr2b ^@ http://purl.uniprot.org/uniprot/Q80ZJ8 ^@ Function|||Similarity ^@ Belongs to the EFCAB4 family.|||Plays a role in store-operated Ca(2+) entry (SOCE). http://togogenome.org/gene/10090:Adam29 ^@ http://purl.uniprot.org/uniprot/G3X9B5 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Zdhhc14 ^@ http://purl.uniprot.org/uniprot/Q8BQQ1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates. May have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and thereby regulate G protein-coupled receptor signaling. May play a role in cell differentiation and apoptosis.|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Pde4b ^@ http://purl.uniprot.org/uniprot/B1AWD0|||http://purl.uniprot.org/uniprot/Q3TTI9|||http://purl.uniprot.org/uniprot/Q6IQY6|||http://purl.uniprot.org/uniprot/Q80VK8|||http://purl.uniprot.org/uniprot/Q8VBU5 ^@ Cofactor|||Similarity ^@ Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions. http://togogenome.org/gene/10090:Traf3ip3 ^@ http://purl.uniprot.org/uniprot/Q8C0G2 ^@ Disruption Phenotype|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays essential roles in both innate and adaptive immunity. Plays a crucial role in the regulation of thymocyte development (PubMed:26195727). Mechanistically, mediates TCR-stimulated activation through recruiting MAP2K1/MEK1 to the Golgi and, thereby, facilitating the interaction of MAP2K1/MEK1 with its activator BRAF (PubMed:26195727). Also plays an essential role in regulatory T-cell stability and function by recruiting the serine-threonine phosphatase catalytic subunit (PPP2CA) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component RPTOR and restricting glycolytic metabolism (PubMed:30115741). Positively regulates TLR4 signaling activity in macrophage-mediated inflammation by acting as a molecular clamp to facilitate LPS-induced translocation of TLR4 to lipid rafts (PubMed:30115741). In response to viral infection, facilitates the recruitment of TRAF3 to MAVS within mitochondria leading to IRF3 activation and interferon production (PubMed:30115741). However, participates in the maintenance of immune homeostasis and the prevention of overzealous innate immunity by promoting 'Lys-48'-dependent ubiquitination of TBK1 (By similarity).|||Cell membrane|||Expressed in bone marrow, spleen and thymus. Not detected in heart, kidney and liver.|||Golgi apparatus membrane|||Interacts (via its coiled-coil domain) with TRAF3 (via isoleucine zipper). Interacts with MAP2K1 (By similarity). Interacts with PPP2CA; this interaction targets PPP2CA to the lysosomes (By similarity). Interacts with MAVS (By similarity). Interacts with TBK1 (By similarity).|||Knockout mice have considerably lower frequencies of CD4(+) and CD8(+) single positive thymocytes, and concomitantly higher frequencies of double positive thymocytes (PubMed:26195727). TRAF3IP3 deletion also affects regulatory T-cell transcriptional programs and stability (PubMed:30115741). In addition, mice show a severely compromised potential to induce interferon production and are vulnerable to RNA virus infection (PubMed:31390091).|||Lysosome membrane|||Mitochondrion outer membrane|||Sequencing errors. http://togogenome.org/gene/10090:Arhgap23 ^@ http://purl.uniprot.org/uniprot/Q69ZH9 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Pip4k2c ^@ http://purl.uniprot.org/uniprot/Q91XU3 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endoplasmic reticulum|||Interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase activity.|||No significant expression was discerned throughout the prenatal brains except for the olfactory mantle zone, which exhibited the expression signals weakly. On P0 and P7, the expression was weakly positive in the gray matter throughout the brain, with higher expression in the olfactory mitral cell layer. In the cerebellum, the expression was evenly positive in external and internal granule cell layers. On P21 and P56, the expression in non-cortical brain parenchyma was negligible. However, the expression was evident in the olfactory mitral cell layer, the piriform cortex, the hippocampal pyramidal CA1-3, and the cerebellar Purkinje cell layer, although much less distinct in the dentate granule cell layer and the cerebellar granule cell layer. In the cerebral cortex, the expression was weaker in layer V than the other layers. No significant expression was seen in the white matter.|||Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic activity. May be a GTP sensor, has higher GTP-dependent kinase activity than ATP-dependent kinase activity. PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3.|||Phosphorylated, phosphorylation is induced by EGF. http://togogenome.org/gene/10090:Tjap1 ^@ http://purl.uniprot.org/uniprot/Q9DCD5 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with DLG1 (By similarity). Interacts with ARF6 (GTP-bound form) (PubMed:22841714).|||Plays a role in regulating the structure of the Golgi apparatus.|||Widely expressed including in adult thymus, heart, lung, liver, small intestine, kidney, spleen, testis and skeletal muscle and in embryonic brain but not detected in adult brain (at protein level).|||tight junction|||trans-Golgi network http://togogenome.org/gene/10090:St8sia1 ^@ http://purl.uniprot.org/uniprot/Q3V3B1|||http://purl.uniprot.org/uniprot/Q64687 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 29 family.|||Catalyzes the addition of sialic acid in alpha 2,8-linkage to the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3; gangliosides are a subfamily of complex glycosphinglolipds that contain one or more residues of sialic acid (PubMed:8910600). Can catalyze the addition of a second alpha-2,8- sialic acid to GD3 to form GT3 (PubMed:8910600). Can use GM1b, GD1a and GT1b as acceptor substrates to synthesize GD1c, GT1a and GQ1b respectively (PubMed:8910600).|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Ufl1 ^@ http://purl.uniprot.org/uniprot/Q8CCJ3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UFL1 family.|||Chromosome|||E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (By similarity). In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane by DDRGK1, and mediates ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting reticulophagy of endoplasmic reticulum sheets (By similarity). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha (By similarity). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response (PubMed:25952549, PubMed:29461087, PubMed:30701081). Regulates inflammation in response to endoplasmic reticulum stress by promoting reticulophagy, leading to inhibit the activity of the NF-kappa-B transcription factor (By similarity). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is a collateral effect or is required for ufmylation (By similarity). Catalyzes ufmylation of various subunits of the ribosomal complex or associated components, such as RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (PubMed:28575669). Anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition (By similarity). Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 (By similarity). Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription (By similarity). Required for hematopoietic stem cell function and hematopoiesis (PubMed:25952549). Required for cardiac homeostasis (PubMed:30354401).|||Embryonic lethality caused by impaired erythroid development (PubMed:25952549). Conditional deletion in adult mice results in severe anemia and cytopenia (PubMed:25952549). Cells show elevated endoplasmic reticulum stress and unfolded protein response in bone marrow cells and impaired autophagic degradation (PubMed:25952549). Conditional knockout in cardiomyocytes causes age-dependent cardiomyopathy and heart failure, characterized by elevated cardiac fetal gene expression, increased fibrosis, and impaired cardiac contractility (PubMed:30354401). When challenged with pressure overload, cardiac-specific knockout mice display greater hypertrophy, exacerbated fibrosis, and worsened cardiac contractility compared to wild-type mice counterparts (PubMed:30354401). Conditional knockout in adults causes a significant loss of both Paneth and goblet cells in intestine, which in turn results in dysbiotic microbiota and increased susceptibility to experimentally induced colitis (PubMed:30701081).|||Endoplasmic reticulum membrane|||Interacts with DDRGK1 (via PCI domain) (By similarity). Interacts with UFC1 (By similarity). Interacts with RELA (By similarity). Interacts with TRIP4 (By similarity). Interacts with CDK5RAP3; the interaction is direct (PubMed:21494687, PubMed:30635284). Interacts with NBN; promoting recruitment to double-strand breaks following DNA damage (By similarity).|||Nucleus|||Phosphorylated at Ser-462 by ATM, enhancing protein ligase activity and promoting ATM activation in a positive feedback loop.|||Ubiquitinated, leading to its degradation by the proteasome. Interaction with CDK5RAP3 protects both proteins against ubiquitination and degradation via the proteasome.|||Ubiquitously expressed with higher expression in pancreatic islets and other secretory tissues (PubMed:20228063, PubMed:21494687). In the embryonic brain at 17 dpc, detected in Sox2-positive neural stem cells and in Slc1a3/GLAST-positive radial glia (PubMed:20531390). In perinatal brain, highly expressed in Slc1a3-positive Bergmann glia of the cerebellum (PubMed:20531390). Continues to be expressed in Bergmann glia of adult brain at 16 weeks (PubMed:20531390). Expressed in adult heart (PubMed:30354401). Highly expressed in the intestinal exocrine cells (PubMed:30701081).|||Up-regulated in hypertrophic hearts (at protein level).|||cytosol http://togogenome.org/gene/10090:Cer1 ^@ http://purl.uniprot.org/uniprot/A2ADM9|||http://purl.uniprot.org/uniprot/O55233 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 6.5 dpc, early and mid-streak stage embryos, was expressed in the anterior visceral endoderm. The expression domain extended from the extraembryonic-embryonic junction to approximately two thirds of the way down the epiblast. By the mid-streak to late streak stage, expressed in the anterior visceral endoderm but was also expressed in the definitive endoderm emanating from the anterior portion of the primitive streak. By the neural plate stage at 7.5 dpc expression was present throughout the anterior definitive endoderm layer including both the midline and anterior lateral endoderm. At the early headfold stage expression was reduced in the anterior lateral region and expression was seen primarily in the foregut endoderm. In early 8.5 dpc embryos, expression was restricted to the two most recently formed somites. In 9 dpc and 9.5 dpc embryos, expression continued in the two newest formed somites and also in the anterior presomitic mesoderm.|||Belongs to the DAN family.|||Cytokine that may play a role in anterior neural induction and somite formation during embryogenesis in part, through a BMP-inhibitory mechanism. Can regulate Nodal signaling during gastrulation as well as the formation and patterning of the primitive streak.|||Forms monomers and predominantly dimers.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Cntn4 ^@ http://purl.uniprot.org/uniprot/Q69Z26 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. Contactin family.|||Cell membrane|||Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity. May be involved in synaptogenesis.|||Expressed from 14 dpc at a time when developing axons reach the olfactory bulb.|||Expressed in the region of developing olfactory neurons. Isoform 2 is expressed in mature sensory cells of the vomeronasal neuroepithelium and at lower level in olfactory neuroepithelium.|||Interacts with PTPRG.|||Secreted http://togogenome.org/gene/10090:Frmpd4 ^@ http://purl.uniprot.org/uniprot/A2AFR3 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in various regions of the brain, including cortex, hippocampus, cerebellum, olfactory bulb and medial habenular nucleus.|||Interacts (via C-terminus) with DLG1, DLG2, DLG3 and DLG4/PSD95. Interacts (via N-terminus) with ARHGEF7; the interaction is mediated by the PDZ domain. Interacts with GPSM2 (via TPR repeat region).|||Positive regulator of dendritic spine morphogenesis and density. Required for the maintenance of excitatory synaptic transmission. Binds phosphatidylinositol 4,5-bisphosphate.|||The FERM domain mediates the interaction with phosphatidylinositol 4,5-bisphosphate.|||dendritic spine http://togogenome.org/gene/10090:Prepl ^@ http://purl.uniprot.org/uniprot/Q8BKS6|||http://purl.uniprot.org/uniprot/Q8C167 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S9A family.|||Golgi apparatus|||Highly expressed in the brain, specifically in neurons of the neocortex, substantia nigra, locus coeruleus, and cerebellum, and a slightly lesser extent in neurons in the hypothalamus and hippocampus (at protein level) (PubMed:23321636, PubMed:23485813). Also expressed in interneurons in the stratum lacunosum moleculare and stratum radiatum (PubMed:23485813).|||Homodimer (By similarity). Interacts with the AP-1 complex (By similarity).|||Inhibited by 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile.|||Nucleus|||PREPL-null mice are significantly shorter and lighter than their wild-type littermates and suffer from neonatal hypotonia.|||Serine peptidase whose precise substrate specificity remains unclear (PubMed:21692504). Does not cleave peptides after a arginine or lysine residue (By similarity). Regulates trans-Golgi network morphology and sorting by regulating the membrane binding of the AP-1 complex (PubMed:23321636). May play a role in the regulation of synaptic vesicle exocytosis (By similarity).|||cytoskeleton|||cytosol|||trans-Golgi network http://togogenome.org/gene/10090:Ptchd4 ^@ http://purl.uniprot.org/uniprot/B9EKX1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the patched family.|||Could act as a repressor of canonical hedgehog signaling by antagonizing the effects of SMO, as suggested by down-regulation of hedgehog target genes, including GLI1, PTCH1, and PTCH2 in PTCHD4-expressing cells.|||Membrane http://togogenome.org/gene/10090:Fsd2 ^@ http://purl.uniprot.org/uniprot/Q8BZ52 ^@ Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed predominantly in heart and skeletal muscle (at protein level).|||Interacts with CMYA5 (PubMed:28740084). In cardiac muscles, identified in a complex composed of FSD2, CMYA5 and RYR2 (PubMed:28740084).|||Nucleus|||Sarcoplasmic reticulum|||perinuclear region http://togogenome.org/gene/10090:Slc35b3 ^@ http://purl.uniprot.org/uniprot/F8WGD7|||http://purl.uniprot.org/uniprot/Q922Q5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.|||Golgi apparatus membrane|||Membrane|||Probably functions as a 3'-phosphoadenylyl sulfate:adenosine 3',5'-bisphosphate antiporter at the Golgi membranes. Mediates the transport from the cytosol into the lumen of the Golgi of 3'-phosphoadenylyl sulfate/adenosine 3'-phospho 5'-phosphosulfate (PAPS), a universal sulfuryl donor for sulfation events that take place in that compartment. http://togogenome.org/gene/10090:Defa35 ^@ http://purl.uniprot.org/uniprot/E9QLQ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Twnk ^@ http://purl.uniprot.org/uniprot/Q8CIW5 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Homohexamer (via C-terminus) which assembled in a ring-like structure. Homoheptamer which assembled in a ring-like structure. Oligomerization is Mg(2+), nucleotide and DNA-independent, however, Mg(2+) and nucleotide stabilize the homohexameric form. Interacts with POLG in vitro. Interacts with LONP1.|||Mitochondrial helicase involved in mtDNA replication and repair (By similarity). Might have a role in mtDNA repair (By similarity). Has DNA strand separation activity needed to form a processive replication fork for leading strand synthesis which is catalyzed by the formation of a replisome complex with POLG and mtSDB (By similarity). Preferentially unwinds DNA substrates with pre-existing 5'-and 3'- single-stranded tails but is also active on a 5'- flap substrate (By similarity). Can dissociate the invading strand of immobile or mobile D-loop DNA structures irrespective of the single strand polarity of the third strand (By similarity). In addition to its DNA strand separation activity, also has DNA strand annealing, DNA strand-exchange and DNA branch migration activities (By similarity).|||N-terminus enhances protein stability and hexamer formation, which is important for DNA binding, and is required for DNA helicase activity and, ultimately, for mtDNA replisome processivity.|||The N-terminus contains a putative primase-like domain; however the absence of the zinc binding domain and other motifs important for catalysis suggests that TWNK lacks primase activity.|||Ubiquitous with the highest levels in the liver, heart and kidneys. The skeletal muscle, brain and testis showed lower but detectable expression. Expression is coregulated with MRPL43.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Msn ^@ http://purl.uniprot.org/uniprot/P26041 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Cell membrane|||Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex. Tethers actin filaments by oscillating between a resting and an activated state providing transient interactions between moesin and the actin cytoskeleton (By similarity). Once phosphorylated on its C-terminal threonine, moesin is activated leading to interaction with F-actin and cytoskeletal rearrangement (By similarity). These rearrangements regulate many cellular processes, including cell shape determination, membrane transport, and signal transduction (By similarity). The role of moesin is particularly important in immunity acting on both T and B-cells homeostasis and self-tolerance, regulating lymphocyte egress from lymphoid organs (PubMed:22875842). Modulates phagolysosomal biogenesis in macrophages (PubMed:28978692). Participates also in immunologic synapse formation (By similarity).|||In resting T-cells, part of a PAG1-NHERF1-MSN complex which is disrupted upon TCR activation (PubMed:11777944). Interacts with NHERF1 (PubMed:11777944). Interacts with PPP1R16B (By similarity). Interacts with PDZD8 (By similarity). Interacts with SELPLG and SYK; these interactions mediate the activation of SYK by SELPLG (By similarity). Interacts with PDPN (via cytoplasmic domain); this interaction activates RHOA and promotes epithelial-mesenchymal transition (By similarity). Interacts with SPN/CD43 cytoplasmic tail (PubMed:9472040). Interacts with CD44 (PubMed:9472040). Interacts with ICAM2 (PubMed:9472040). Interacts with ICAM3 (via C-terminus) (By similarity). Interacts with PDZD8 (By similarity). Interacts with F-actin (By similarity). Interacts with CD46 (By similarity). Interacts with PTPN6 (PubMed:29247647).|||Moesin-deficient mice exhibit no obvious abnormalities in appearance or fertility, but display altered humoral immune responses.|||Phosphorylation on Thr-558 by STK10 negatively regulates lymphocyte migration and polarization (By similarity). Phosphorylation on Thr-558 is crucial for the formation of microvilli-like structures. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding.|||S-nitrosylation of Cys-117 is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) implicating the iNOS-S100A8/9 transnitrosylase complex.|||The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.|||cytoskeleton|||microvillus|||microvillus membrane http://togogenome.org/gene/10090:Rilpl2 ^@ http://purl.uniprot.org/uniprot/Q99LE1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RILPL family.|||Homodimer (PubMed:23798443). Interacts with RAC1 (By similarity). Interacts (via N-terminus) with MYO5A, the interaction is required for its role in dendrite formation (PubMed:23798443). Interacts with RAB8A; interaction is dependent on the phosphorylation of RAB8A on 'Thr-72' (PubMed:29125462). Interacts with RAB10 and RAB12; interaction is dependent on the phosphorylation of 'Thr-73' on RAB10 and 'Ser-105' on RAB12 (By similarity).|||Involved in cell shape and neuronal morphogenesis, positively regulating the establishment and maintenance of dendritic spines (By similarity). Plays a role in cellular protein transport, including protein transport away from primary cilia (PubMed:23264467). May function via activation of RAC1 and PAK1 (By similarity).|||centrosome|||cilium|||cytosol http://togogenome.org/gene/10090:Majin ^@ http://purl.uniprot.org/uniprot/Q9D992 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MAJIN family.|||Component of the MAJIN-TERB1-TERB2 complex, composed of MAJIN, TERB1 and TERB2.|||MAJIN was named after the 'genie in Aladdin's lamp' in Japanese.|||Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA. In the complex, MAJIN acts as the anchoring subunit to the nucleus inner membrane. MAJIN shows DNA-binding activity, possibly for the stabilization of telomere attachment on the nucleus inner membrane.|||Mice develop normally, exhibit no overt phenotype, but are infertile (both males and females). Gonads are characterized by the absence of post-meiotic cells. Impaired localization of Terb1 and Terb2 to the nucleus inner membrane.|||Nucleus inner membrane|||Specifically expressed in germline tissues.|||telomere http://togogenome.org/gene/10090:Or10n1 ^@ http://purl.uniprot.org/uniprot/Q05AA1|||http://purl.uniprot.org/uniprot/Q60887 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Odorant receptor. http://togogenome.org/gene/10090:Sh3gl3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0B8|||http://purl.uniprot.org/uniprot/Q497N4|||http://purl.uniprot.org/uniprot/Q62421|||http://purl.uniprot.org/uniprot/Q9CZV7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes.|||Belongs to the endophilin family.|||Cytoplasm|||Early endosome membrane|||Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity).|||Interacts with ARC, DNM1, SGIP1, SYNJ1 and DYDC1. Interacts with FASLG (By similarity). Interacts with ATXN2. Interacts with BIN2 (By similarity).|||Membrane http://togogenome.org/gene/10090:Scn7a ^@ http://purl.uniprot.org/uniprot/B1AYL1|||http://purl.uniprot.org/uniprot/Q62467 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Membrane http://togogenome.org/gene/10090:Tspoap1 ^@ http://purl.uniprot.org/uniprot/Q7TNF8 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RIMBP family.|||Cytoplasm|||Due to intron retention.|||Interacts with RIMS1, RIMS2 and TSPO.|||Mitochondrion|||Predominantly expressed in the brain.|||The SH3 and proline-rich domain is required for the interaction with TSPO and the second SH3 domain mediates binding to a proline-rich motif in RIMS1 and RIMS2. http://togogenome.org/gene/10090:Setd3 ^@ http://purl.uniprot.org/uniprot/Q91WC0 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. SETD3 actin-histidine methyltransferase family.|||Cytoplasm|||Expression is repressed by microRNAs miR-15b and miR-322, repressing muscle cell differentiation.|||Interacts with MYOD1.|||Mice are viable, but females display severely decreased litter sizes due to primary maternal dystocia (delayed parturition) that is refractory to ecbolic induction agents (PubMed:30626964). Cells show complete loss of actin histidine methylation (PubMed:30626964).|||Nucleus|||Phosphorylated by GSK3B, which is required for recognition by the SCF(FBXW7) complex and subsequent degradation.|||Prominently expressed in the heart and skeletal muscles and is also detected weakly in the stomach, small intestine, and colon.|||Protein-histidine N-methyltransferase that specifically mediates 3-methylhistidine (tele-methylhistidine) methylation of actin at 'His-73' (PubMed:30626964). Histidine methylation of actin is required for smooth muscle contraction of the laboring uterus during delivery (PubMed:30626964). Does not have protein-lysine N-methyltransferase activity and probably only catalyzes histidine methylation of actin (PubMed:30626964).|||The SET domain specifically recognizes and binds actin, suggesting that it does not accommodate substrates diverging from actin.|||Ubiquitinated by the SCF(FBXW7) complex following phosphorylation by GSK3B, leading to its degradation by the proteasome.|||Was initially reported to have histone methyltransferase activity and methylate 'Lys-4' and 'Lys-36' of histone H3 (H3K4me and H3K36me) (PubMed:21832073). However, this conclusion was based on mass spectrometry data wherin mass shifts were inconsistent with a bona fide methylation event and the histone methyltransferase activity could not be confirmed (PubMed:30626964). http://togogenome.org/gene/10090:Tatdn1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1E8|||http://purl.uniprot.org/uniprot/Q6P8M1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.|||Binds 2 divalent metal cations per subunit.|||Deoxyribonuclease which catalyzes (in vitro) the decatenation of kinetoplast DNA, which are circular DNA catenated to each other, producing linear DNA molecules (By similarity). Plays an important role in chromosomal segregation and cell cycle progression during eye development probably via its DNA decatenation activity (By similarity).|||Nucleus http://togogenome.org/gene/10090:Pole2 ^@ http://purl.uniprot.org/uniprot/O54956 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory component of the DNA polymerase epsilon complex (By similarity). Participates in DNA repair and in chromosomal DNA replication (By similarity).|||Belongs to the DNA polymerase epsilon subunit B family.|||Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4.|||In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.|||Nucleus http://togogenome.org/gene/10090:Rlig1 ^@ http://purl.uniprot.org/uniprot/Q8BHN7 ^@ Function|||PTM ^@ AMPylates itself (auto-AMPylation).|||Functions as an RNA ligase, in vitro. The ligation reaction entails three nucleotidyl transfer steps. In the first step, the RNA ligase reacts with ATP in the absence of nucleic acid to form a covalent ligase-AMP intermediate and release pyrophosphate. In step 2, the ligase-AMP binds to the nucleic acid and transfers the adenylate to the 5'-PO4 terminus to form an adenylylated intermediate. In step 3, the RNA ligase directs the attack of the 3'-OH on the 5'-phosphoanhydride linkage, resulting in a repaired 3'-5' phosphodiester and release of AMP. Exhibits selectivity for single-stranded RNA substrates and may not have nick-sealing activity on double-stranded DNA-RNA hybrids. May play a role in maintaining RNA integrity under stress conditions, for example in response to reactive oxygen species (ROS). http://togogenome.org/gene/10090:Ppara ^@ http://purl.uniprot.org/uniprot/P23204|||http://purl.uniprot.org/uniprot/Q542P9 ^@ Developmental Stage|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with NCOA3 coactivator. Interacts with CITED2; the interaction stimulates its transcriptional activity. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the interaction seems to be modulated by NAD(+) levels (By similarity). Interacts with CRY1 and CRY2 (PubMed:28683290).|||Highly expressed in liver, kidney and heart. Very weakly expressed in brain and testis.|||It appears first at 13.5 dpc and increases until birth.|||Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.|||Nucleus|||Peroxisome proliferators are a diverse group of chemicals that include hypolipidaemic drugs, herbicides and industrial plasticisers. Administration of these chemicals to rodents results in the dramatic proliferation of hepatic peroxisomes as well as liver hyperplasia. http://togogenome.org/gene/10090:Wfdc13 ^@ http://purl.uniprot.org/uniprot/Q5DQQ6 ^@ Function|||Subcellular Location Annotation ^@ Putative acid-stable proteinase inhibitor.|||Secreted http://togogenome.org/gene/10090:Cope ^@ http://purl.uniprot.org/uniprot/O89079 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COPE family.|||COPI-coated vesicle membrane|||Cytoplasm|||Golgi apparatus membrane|||Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.|||Phosphorylated by PKA.|||Polyubiquitinated by RCHY1 in the presence of androgen, leading to proteasomal degradation.|||The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated with ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). http://togogenome.org/gene/10090:Fam178b ^@ http://purl.uniprot.org/uniprot/E9PUL8|||http://purl.uniprot.org/uniprot/E9PXB2|||http://purl.uniprot.org/uniprot/Q24JP3 ^@ Similarity ^@ Belongs to the FAM178 family. http://togogenome.org/gene/10090:Mc4r ^@ http://purl.uniprot.org/uniprot/P56450 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with ATRNL1. Homodimer; disulfide-linked, also forms higher order oligomers. Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production (By similarity). Interacts with MRAP and MRAP2; these associated factors increase ligand-sensitivity and generation of cAMP.|||Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP). http://togogenome.org/gene/10090:Gfy ^@ http://purl.uniprot.org/uniprot/J3KML8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ First expressed at embryonic day (E) 11.5 in the olfactory epithelium and at 13.5 dpc in the vomeronasal organ. Expression increases thereafter, reached maximal level at P14, and strong expression level is maintained into adulthood.|||Golgi apparatus membrane|||Required for proper function of the olfactory system. May be involved in establishing the acuity of olfactory sensory signaling.|||Specifically expressed in the olfactory epithelium and vomeronasal organ throughout development. Expressed in both immature and mature olfactory sensory neurons in the olfactory epithelium (at protein level).|||Various olfactory phenotypes, such as abnormal localization of ADCY3, shortened olfactory cilia, and reduced electrophysiological and behavioral sensitivities to odorants. http://togogenome.org/gene/10090:Hbb-bh1 ^@ http://purl.uniprot.org/uniprot/P04444|||http://purl.uniprot.org/uniprot/Q5EBL1 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the globin family.|||Heterotetramer of two alpha chains and two beta chains.|||Red blood cells.|||This is an embryonic beta-type chain. http://togogenome.org/gene/10090:Fam53b ^@ http://purl.uniprot.org/uniprot/Q8BGR5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization.|||Belongs to the FAM53 family.|||Interacts with CTNNB1.|||Nucleus http://togogenome.org/gene/10090:Mroh2b ^@ http://purl.uniprot.org/uniprot/Q7M6Y6 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Constitutively phosphorylated on serine and threonine residues in acrosomal region of the sperm head, midpiece and flagellar regions of noncapacitated spermatozoa. Phosphorylation on tyrosine residues increases upon sperm capacitation within the acrosomal and tail regions in a protein kinase A (PKA)-dependent signaling pathway.|||Cytoplasm|||Embryonically lethal before 10 dpc.|||Expressed strongly in round spermatids and fully mature spermatozoa. Expressed weakly in pachytene spermatocytes (at protein level). Isoform 2 is specifically expressed in the testis. Isoform 2 is expressed in pachytene spermatocytes and round spermatids. Isoform 3 is weakly expressed in testis.|||Found in a complex at least composed of MROH2B isoform 2, PRKACA isoform 2 and TCP11 (PubMed:27105888). Interacts with PRKACA isoform 2 (PubMed:27105888). Interacts with TCP11 (PubMed:27105888).|||May play a role in the process of sperm capacitation (PubMed:27105888).|||acrosome|||flagellum http://togogenome.org/gene/10090:Gsg1 ^@ http://purl.uniprot.org/uniprot/Q8R1W2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GSG1 family.|||Endoplasmic reticulum membrane|||Expressed in spermatogenic cells (at protein level). Expressed in germ cells within the testis from day 21 onwards.|||Interacts with PAPOLB.|||May cause the redistribution of PAPOLB from the cytosol to the endoplasmic reticulum. http://togogenome.org/gene/10090:Triml1 ^@ http://purl.uniprot.org/uniprot/Q8BVP1 ^@ Developmental Stage|||Function|||Subunit|||Tissue Specificity ^@ Expressed from two-cell to blastocyst stage of embryo development.|||Interacts with USP5.|||Probable E3 ubiquitin-protein ligase which plays an important role in blastocyst development. Involved in progression of blastocyst stage and subsequent embryo development.|||Testis. http://togogenome.org/gene/10090:Dimt1 ^@ http://purl.uniprot.org/uniprot/Q9D0D4 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.|||Introns retention.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Specifically dimethylates two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA in the 40S particle. Involved in the pre-rRNA processing steps leading to small-subunit rRNA production independently of its RNA-modifying catalytic activity. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Lat ^@ http://purl.uniprot.org/uniprot/O54957 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Lys-63'-linked ubiquitinated by TRAF6.|||Cell membrane|||Engagement of killer inhibitory receptors (KIR) disrupts the interaction of PLCG1 with LAT and blocks target cell-induced activation of PLC, maybe by inducing the dephosphorylation of LAT.|||Expressed in T-cells and mast cells.|||Palmitoylation of Cys-27 and Cys-30 is required for raft targeting and efficient phosphorylation.|||Phosphorylated on tyrosines by ZAP70 upon TCR activation, or by SYK upon other immunoreceptor activation; which leads to the recruitment of multiple signaling molecules. Is one of the most prominently tyrosine-phosphorylated proteins detected following TCR engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK leading to the recruitment of VAV1 to LAT-containing complexes (By similarity).|||Phosphorylated on tyrosines by ZAP70 upon TCR activation, or by SYK upon other immunoreceptor activation; which leads to the recruitment of multiple signaling molecules. Is one of the most prominently tyrosine-phosphorylated proteins detected following TCR engagement. May be dephosphorylated by PTPRJ. Phosphorylated by ITK leading to the recruitment of VAV1 to LAT-containing complexes.|||Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development. Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules.|||When phosphorylated, interacts directly with the PIK3R1 subunit of phosphoinositide 3-kinase and the SH2 domains of GRB2, GRAP, GRAP2, PLCG1 and PLCG2. Interacts indirectly with CBL, SOS, VAV, and LCP2. Interacts with SHB and SKAP2. Interacts with FCGR1A (By similarity). Interacts with CLNK. Interacts with GRB2, PLCG1 and THEMIS upon TCR activation in thymocytes. Interacts with THEMIS2 (PubMed:22732588). http://togogenome.org/gene/10090:Chrnb2 ^@ http://purl.uniprot.org/uniprot/Q9ERK7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodiun ions.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-2/CHRNB2 sub-subfamily.|||Cell membrane|||Neuronal AChR is composed of two different types of subunits: alpha and beta. Beta-2 subunit can be combined to alpha-2, alpha-3 or alpha-4 to give rise to functional receptors, complexes with beta-2 may be heteropentamers. Alpha-2/4:beta-2 nAChR complexes are proposed to exist in two subtypes: LS (low agonist sensitivity) with a (alpha-2/4)3:(beta-2)2 and HS (high agonist sensitivity) with a (alpha-2/4)2:(beta-2)3 stoichiometry; the subtypes differ in their subunit binding interfaces which are involved in ligand binding. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6. The heteropentamer alpha3-beta-2 interacts with alpha-cconotoxins BuIA, MII, ImI, ImII, PnIA and GID (By similarity). The heteropentamer alpha-4-beta-2 interacts with the alpha-conotoxins PnIA, GID and MII (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Gpr15 ^@ http://purl.uniprot.org/uniprot/Q0VDU3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Probable chemokine receptor. http://togogenome.org/gene/10090:Eif4ebp1 ^@ http://purl.uniprot.org/uniprot/Q60876 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eIF4E-binding protein family.|||Cytoplasm|||Highest expression in fat cells.|||Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:7629182). Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:24139800).|||Mice lacking both Eif4ebp1 and Eif4ebp2 display increased their sensitivity to diet-induced obesity (PubMed:17273556). Mice lacking both Eif4ebp1 and Eif4ebp2 show defects in myelopoiesis: mice display an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements (PubMed:19175792).|||Nucleus|||Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-36, Thr-45, Ser-64 and Thr-69, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.|||Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (PubMed:7629182).|||The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.|||Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E. http://togogenome.org/gene/10090:Naa80 ^@ http://purl.uniprot.org/uniprot/Q9R123 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the acetyltransferase family.|||N-alpha-acetyltransferase that specifically mediates the acetylation of the acidic amino terminus of processed forms of beta- and gamma-actin (ACTB and ACTG, respectively). N-terminal acetylation of processed beta- and gamma-actin regulates actin filament depolymerization and elongation. In vivo, preferentially displays N-terminal acetyltransferase activity towards acid N-terminal sequences starting with Asp-Asp-Asp and Glu-Glu-Glu. In vitro, shows high activity towards Met-Asp-Glu-Leu and Met-Asp-Asp-Asp. May act as a tumor suppressor.|||cytosol http://togogenome.org/gene/10090:Rnf214 ^@ http://purl.uniprot.org/uniprot/Q8BFU3 ^@ Miscellaneous|||Sequence Caution ^@ Intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. http://togogenome.org/gene/10090:Dact1 ^@ http://purl.uniprot.org/uniprot/D3Z5V0|||http://purl.uniprot.org/uniprot/Q8R4A3 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dapper family.|||Can form homodimers and heterodimers with DACT2 or DACT3. Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, CSNK2A1, CSNK2B, DVL1, DLV2, DVAL3, VANGL1, VANGL2, CTNND1 and HDAC1. Interacts with GSK3B; the interaction is indicative for an association of DACT1 with the beta-catenin destruction complex. Interacts with GSK3A. Interacts with YWHAB; the interaction is enhanced by PKA phosphorylating DACT1 at Ser-769. Interacts with CTNNB1 (By similarity).|||Cytoplasm|||Expressed in multiple tissues including brain, heart, kidney, liver and testis.|||Expression strongly increases from 9.5 dpc, peaks between 11.5 dpc and 13.5 dpc and diminishes slowly thereafter. Expressed in the somites during segmentation, limb bud mesenchyme, and developing central nervous system. Expressed in primitive streak mesoderm, neuroectoderm, neural crest, presomitic mesoderm and somites.|||Involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins. The activation/inhibition of Wnt signaling may depend on the phosphorylation status. Proposed to regulate the degradation of CTNNB1/beta-catenin, thereby modulating the transcriptional activation of target genes of the Wnt signaling pathway. Its function in stabilizing CTNNB1 may involve inhibition of GSK3B activity. Promotes the membrane localization of CTNNB1. The cytoplasmic form can induce DVL2 degradation via a lysosome-dependent mechanism; the function is inhibited by PKA-induced binding to 14-3-3 proteins, such as YWHAB (By similarity). Seems to be involved in morphogenesis at the primitive streak by regulating VANGL2 and DVL2; the function seems to be independent of canonical Wnt signaling and rather involves the non-canonical Wnt/planar cell polarity (PCP) pathway. The nuclear form may prevent the formation of LEF1:CTNNB1 complex and recruit HDAC1 to LEF1 at target gene promoters to repress transcription thus antagonizing Wnt signaling (By similarity). May be involved in positive regulation of fat cell differentiation. During neuronal differentiation may be involved in excitatory synapse organization, and dendrite formation and establishment of spines.|||Mice die within a day of birth with malformations involving the spine, genitourinary system and distal digestive tract due to disrupted germ-layer morphogenesis at the primitive streak where cells undergo an epithelial-mesenchymal transition. Urogenital defects due to impaired hindgut formation start at embryonic day 8.25. Dvl2 and Vangl2 are found increased at the primitive streak, associated with abnormal distribution of E-cadherin.|||Nucleus|||Synapse|||The C-terminal PDZ-binding motif mediates interaction with the PDZ domains of DSH (Dishevelled) family proteins. http://togogenome.org/gene/10090:Naalad2 ^@ http://purl.uniprot.org/uniprot/Q3UZV6|||http://purl.uniprot.org/uniprot/Q9CZR2 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M28 family. M28B subfamily.|||Binds 2 Zn(2+) ions per subunit. Required for NAALADase activity.|||Cell membrane|||Expressed ovary, testes and lung, but not brain.|||Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivates the peptide neurotransmitter N-acetylaspartylglutamate.|||Homodimer.|||Membrane|||The NAALADase activity is found in the central region, the dipeptidyl peptidase IV type activity in the C-terminal. http://togogenome.org/gene/10090:4930579G24Rik ^@ http://purl.uniprot.org/uniprot/Q3UUX7 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Vmn2r98 ^@ http://purl.uniprot.org/uniprot/E9PZ56 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mphosph10 ^@ http://purl.uniprot.org/uniprot/Q810V0|||http://purl.uniprot.org/uniprot/Q9CYN7|||http://purl.uniprot.org/uniprot/Q9D7V6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MPP10 family.|||Chromosome|||Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Component of a heterotrimeric complex containing IMP3, IMP4 and MPHOSPH10. Interacts with IMP3 and IMP4.|||Phosphorylated in M (mitotic) phase.|||nucleolus http://togogenome.org/gene/10090:Plaat5 ^@ http://purl.uniprot.org/uniprot/Q9CPX5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the H-rev107 family.|||Exhibits both phospholipase A1/2 and acyltransferase activities (By similarity). Shows phospholipase A1 (PLA1) and A2 (PLA2) activity, catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (By similarity). Shows N-acyltransferase activity, catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (PubMed:19000777).|||Isoform 4 shows highest expression level in testis.|||cytosol http://togogenome.org/gene/10090:Tcea2 ^@ http://purl.uniprot.org/uniprot/Q810R3|||http://purl.uniprot.org/uniprot/Q9QVN7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TFS-II family.|||Expressed in testicular germ cells during and after meiosis in the course of spermatogenesis, while it is not expressed in premeiotic or early meiotic testicular germ cells.|||Interacts with the basal transcription factor GTF2B. Interacts with REXO1 (By similarity).|||Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.|||Nucleus|||Testis and ovary specific. Specific to testicular germ cells. http://togogenome.org/gene/10090:Gch1 ^@ http://purl.uniprot.org/uniprot/Q05915|||http://purl.uniprot.org/uniprot/Q3U7P6 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTP cyclohydrolase I family.|||Cytoplasm|||GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg(2+).|||May positively regulate nitric oxide synthesis in endothelial cells. May be involved in dopamine synthesis. May modify pain sensitivity and persistence.|||Nucleus|||Phosphorylated.|||Toroid-shaped homodecamer, composed of two pentamers of five dimers. Interacts with AHSA1 and GCHFR/GFRP. http://togogenome.org/gene/10090:Sema3c ^@ http://purl.uniprot.org/uniprot/Q62181 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the semaphorin family.|||Binds to plexin family members and plays an important role in the regulation of developmental processes. Required for normal cardiovascular development during embryogenesis. Functions as attractant for growing axons, and thereby plays an important role in axon growth and axon guidance.|||Expressed from day 10 in the embryo. Maximum expression between days 10-12 with moderate levels from day 13 until birth.|||Interacts with PLXND1.|||Perinatal lethality. Mice display severe defects in cardiovascular development, including aortic arch malformations and septation defects in the cardiac outflow tract.|||Secreted http://togogenome.org/gene/10090:Exd2 ^@ http://purl.uniprot.org/uniprot/Q8VEG4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EXD2 family.|||Chromosome|||Divalent metal cations; Mg(2+) or Mn(2+). Acts as a 3'-5' exoribonuclease in presence of Mg(2+), while it has no 3'-5' exodeoxyribonuclease activity. Has both as a 3'-5' exoribonuclease and exodeoxyribonuclease activities in presence of Mn(2+).|||Exonuclease that has both 3'-5' exoribonuclease and exodeoxyribonuclease activities, depending on the divalent metal cation used as cofactor. In presence of Mg(2+), only shows 3'-5' exoribonuclease activity, while it shows both exoribonuclease and exodeoxyribonuclease activities in presence of Mn(2+). Acts as an exoribonuclease in mitochondrion, possibly by regulating ATP production and mitochondrial translation. Also involved in the response to DNA damage. Acts as 3'-5' exodeoxyribonuclease for double-strand breaks resection and efficient homologous recombination. Plays a key role in controlling the initial steps of chromosomal break repair, it is recruited to chromatin in a damage-dependent manner and functionally interacts with the MRN complex to accelerate resection through its 3'-5' exonuclease activity, which efficiently processes double-stranded DNA substrates containing nicks. Also involved in response to replicative stress: recruited to stalled forks and is required to stabilize and restart stalled replication forks by restraining excessive fork regression, thereby suppressing their degradation.|||Homodimer. Interacts with RBBP8, MRE11 and BRCA1.|||Mitochondrion matrix|||Mitochondrion outer membrane|||Nucleus http://togogenome.org/gene/10090:Plek ^@ http://purl.uniprot.org/uniprot/Q9JHK5 ^@ Function ^@ Major protein kinase C substrate of platelets. http://togogenome.org/gene/10090:Limd2 ^@ http://purl.uniprot.org/uniprot/Q8BGB5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as an activator of the protein-kinase ILK, thereby regulating cell motility.|||Cytoplasm|||Interacts with ILK.|||Nucleus http://togogenome.org/gene/10090:Smim15 ^@ http://purl.uniprot.org/uniprot/Q3UTD9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SMIM15 family.|||Membrane http://togogenome.org/gene/10090:Thyn1 ^@ http://purl.uniprot.org/uniprot/Q8BJZ7|||http://purl.uniprot.org/uniprot/Q91YJ3 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Down-regulated upon induction of apoptosis.|||Expressed in the medulla containing mature thymocytes, but not the cortex having immature thymocytes (at protein level). Abundant expression seen in testis, liver, brain and kidney with lower levels of the expression in thymus, spleen, heart and stomach.|||Nucleus|||Phosphorylated.|||Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC. http://togogenome.org/gene/10090:Polr1d ^@ http://purl.uniprot.org/uniprot/P97304|||http://purl.uniprot.org/uniprot/Q545W2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I) and RNA polymerase III (Pol III) complexes consisting of at least 13 and 17 subunits, respectively.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common core component of RNA polymerases I and III which synthesize ribosomal RNA precursors and small RNAs, such as 5S rRNA and tRNAs, respectively.|||Nucleus http://togogenome.org/gene/10090:Snx3 ^@ http://purl.uniprot.org/uniprot/Q78ZM0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||Early endosome|||Endosome|||phagosome http://togogenome.org/gene/10090:Adamts4 ^@ http://purl.uniprot.org/uniprot/Q8BNJ2 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Cleaves aggrecan at the '392-Glu-|-Ala-393' site (By similarity).|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||In embryonic skeletal muscle, significantly increased levels between 13.5 dpc and 15.5 dpc with maximal expression observed at 15.5 dpc (PubMed:23233679). Decreased levels in postnatal skeletal muscle (PubMed:23233679). In myoblasts, up-regulated soon after induction of myoblast differentiation (PubMed:23233679).|||Interacts with SRPX2.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Cyfip1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J119|||http://purl.uniprot.org/uniprot/Q7TMB8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CYFIP family.|||Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. May act as an invasion suppressor in cancers. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (PubMed:27605705).|||Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the CYFIP1-EIF4E-FMR1 complex which is composed of CYFIP, EIF4E and FMR1. Interacts with FMR1 but does not bind to related proteins FXR1 or FXR2. Interaction with EIF4E stimulates FMR1 binding. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1L/HEM1 in hematopoietic cells) and WASF2/WAVE2. Interacts with the active GTP-bound form of RAC1. Interacts through its C-terminus with the C-terminus of DPYSL2/CRMP2 which is necessary for DPYSL2-induced axon outgrowth. Interacts with NYAP1, NYAP2 and MYO16. Interacts with TMEM108 (via N-terminus); the interaction associates TMEM108 with the WAVE1 complex (PubMed:27605705).|||Cytoplasm|||Highly expressed in embryonic and adult developing nervous system.|||Mice display greatly reduced lamellipodium formation in response to growth factor stimulation or aluminum fluoride treatment. Abnormal epithelial morphogenesis in vitro, and cooperation with oncogenic Ras to produce invasive carcinomas in vivo.|||lamellipodium|||perinuclear region|||ruffle|||synaptosome http://togogenome.org/gene/10090:Haus8 ^@ http://purl.uniprot.org/uniprot/Q99L00 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HAUS8 family.|||Component of the HAUS augmin-like complex. The complex interacts with the gamma-tubulin ring complex and this interaction is required for spindle assembly. Associates with microtubules. The interaction with microtubules is strong during mitosis, while it is weak or absent during interphase. It is unclear whether this interaction is direct or indirect (By similarity). Interacts with EML3 (phosphorylated at 'Thr-882') and TUBG1 (By similarity).|||Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex.|||Cytoplasm|||centrosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Eipr1 ^@ http://purl.uniprot.org/uniprot/Q8K0G5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network (By similarity). Mediates the recruitment of Golgi-associated retrograde protein (GARP) complex to the trans-Golgi network and controls early endosome-to-Golgi transport of internalized protein (By similarity). Promotes the recycling of internalized transferrin receptor (TFRC) to the plasma membrane through interaction with endosome-associated recycling protein (EARP) complex (By similarity). Controls proper insulin distribution and secretion, and retention of cargo in mature dense core vesicles (By similarity). Required for the stability of the endosome-associated retrograde protein (EARP) complex subunits and for proper localization and association of EARP with membranes (By similarity).|||Belongs to the WD repeat EIPR1 family.|||Interacts with two multisubunit tethering complexes: EARP composed of VPS50, VPS51, VPS52 and VPS53 subunits and GARP complex composed of VPS51, VPS52, VPS53 and VPS54 subunits. Interacts with SNAP29.|||trans-Golgi network http://togogenome.org/gene/10090:Smad3 ^@ http://purl.uniprot.org/uniprot/Q8BUN5 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.|||Belongs to the dwarfin/SMAD family.|||Cytoplasm|||Highly expressed in the brain and ovary. Detected in the pyramidal cells of the hippocampus, granule cells of the dentate gyrus, granular cells of the cerebral cortex and the granulosa cells of the ovary.|||Monomer; in the absence of TGF-beta (By similarity). Homooligomer; in the presence of TGF-beta (By similarity). Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex (PubMed:21145499). Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:15496141). Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta (By similarity). Found in a complex composed of SMAD3, RAN and XPO4; within the complex interacts directly with XPO4 (By similarity). Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta (By similarity). Part of a ternary complex composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4; the complex mediates ubiquitination and proteasomal degradation of NEDD9/HEF1 (By similarity). Interacts with NEDD9; the interaction promotes NEDD9 ubiquitination and proteasomal degradation (By similarity). Interacts (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta (By similarity). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (By similarity). Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling (By similarity). Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (By similarity). Interacts (when phosphorylated) with RNF111; RNF111 acts as an enhancer of the transcriptional responses by mediating ubiquitination and degradation of SMAD3 inhibitors (PubMed:17341133). Interacts (dephosphorylated form via the MH1 and MH2 domains) with RANBP3 (via its C-terminal R domain); the interaction results in the export of dephosphorylated SMAD3 out of the nucleus and termination of the TGF-beta signaling (By similarity). Interacts (via MH2 domain) with LEMD3; the interaction represses SMAD3 transcriptional activity through preventing the formation of the heteromeric complex with SMAD4 and translocation to the nucleus (By similarity). Interacts (via the linker region) with EP300 (C-terminal); the interaction promotes SMAD3 acetylation and is enhanced by TGF-beta phosphorylation in the C-terminal of SMAD3 (By similarity). This interaction can be blocked by competitive binding of adenovirus oncoprotein E1A to the same C-terminal site on EP300, which then results in partially inhibited SMAD3/SMAD4 transcriptional activity (By similarity). Interacts with TGFBR1 (By similarity). Interacts with TGFB1I1 (PubMed:14755691). Interacts with PRDM16 (PubMed:17467076). Interacts with SNW1 (By similarity). Interacts (via MH2 domain) with ZFYVE9 (PubMed:15356634). Interacts with HDAC1 (By similarity). Interacts with TGIF2 (By similarity). Interacts with SKOR1 (By similarity). Interacts with SKOR2 (By similarity). Interacts with DACH1; the interaction inhibits the TGF-beta signaling (By similarity). Interacts with RBPMS (By similarity). Interacts (via MH2 domain) with MECOM (By similarity). Interacts with WWTR1 (via its coiled-coil domain) (By similarity). Interacts with SKI; the interaction represses SMAD3 transcriptional activity (By similarity). Interacts with MEN1 (By similarity). Interacts with IL1F7 (By similarity). Interaction with CSNK1G2 (By similarity). Interacts with PDPK1 (via PH domain) (By similarity). Interacts with DAB2; the interactions are enhanced upon TGF-beta stimulation (By similarity). Interacts with USP15 (By similarity). Interacts with PPP5C; the interaction decreases SMAD3 phosphorylation and protein levels (PubMed:22781750). Interacts with LDLRAD4 (via the SMAD interaction motif) (By similarity). Interacts with PMEPA1 (By similarity). Interacts with ZNF451 (By similarity). Interacts with ZFHX3 (By similarity). Interacts weakly with ZNF8 (PubMed:12370310). Interacts with STUB1, HSPA1A, HSPA1B, HSP90AA1 and HSP90AB1 (By similarity). Interacts with YAP1 (when phosphorylated at 'Ser-112') (PubMed:21145499). Interacts with MAGI2/ARIP1 (PubMed:10681527). Interacts (via MH2 domain) with CITED2 (via C-terminus) (By similarity). Interacts with HGS (PubMed:11094085). Interacts with WWP1 (PubMed:15221015). Interacts with TTRAP (PubMed:18039968). Interacts with FOXL2 (PubMed:19106105). Interacts with PML (PubMed:15356634). Interacts with NEDD4L; the interaction requires TGF-beta stimulation (PubMed:15496141). Interacts with ZC3H3 (PubMed:16115198). Interacts with TGIF. Interacts with CREBBP. Interacts with ATF2. Interacts with NEDD9; the interaction is inhibited by oxidation of NEDD9 (By similarity).|||Nucleus|||Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses (By similarity). Phosphorylated by PDPK1 (By similarity).|||Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.|||Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity).|||SMAD3 null mice exhibit inhibition of proliferation of mammary gland epithelial cells. Fibrobasts are only partially growth inhibited. Defects in osteoblast differentiation are observed. Animals are osteopenic with less cortical and cancellous bone. Facture healing is accelerated. Decreased bone mineral density (BMD) reflects the inability of osteoblasts to balance osteoclast activity. Wound healing is accelerated to about two and a half times that of normal animals. Wound areas are significantly reduced with less quantities of granulation tissue. There is reduced local infiltration of moncytes and keratinocytes show altered patterns of growth and migration. Accelerated wound healing is observed on castration of null male mice, while null female mice exhibited delayed healing following ovariectomy.|||The MH1 domain is required for DNA binding (By similarity). Also binds zinc ions which are necessary for the DNA binding.|||The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import (By similarity).|||The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.|||Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding. Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (By similarity). Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover (PubMed:17341133). Undergoes STUB1-mediated ubiquitination and degradation (By similarity). http://togogenome.org/gene/10090:Gm10487 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Ints15 ^@ http://purl.uniprot.org/uniprot/Q8BGA7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Probable component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing.|||Probable component of the multiprotein Integrator (INT) complex. http://togogenome.org/gene/10090:Mbnl1 ^@ http://purl.uniprot.org/uniprot/Q9JKP5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the muscleblind family.|||Cytoplasm|||Cytoplasmic granule|||Highly expressed in cardiac and skeletal muscle. Weakly expressed in heart and eye (at protein level).|||Interacts with DDX1 and YBX1. Interacts with HNRNPH1; the interaction in RNA-independent (By similarity).|||Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y-3'consensus sequence. Binds to the IR RNA. Binds to CUG triplet repeat expansion in myotonic dystrophy muscle cells by sequestering the target RNAs (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gale ^@ http://purl.uniprot.org/uniprot/Q8R059 ^@ Function|||Similarity|||Subunit ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family.|||Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids.|||Homodimer. http://togogenome.org/gene/10090:Dusp5 ^@ http://purl.uniprot.org/uniprot/Q1HL35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Nucleus http://togogenome.org/gene/10090:Epn1 ^@ http://purl.uniprot.org/uniprot/Q80VP1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the epsin family.|||Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis (By similarity).|||Cell membrane|||Cytoplasm|||Monomer. Binds clathrin and ZBTB16/ZNF145 (By similarity). Binds ubiquitinated proteins (By similarity). Interacts with RALBP1 in a complex also containing NUMB and TFAP2A during interphase and mitosis (By similarity). Interacts with AP2B1 (By similarity). Interacts with UBQLN2 (By similarity). Interacts with ITSN1. Interacts with AP2A1 and AP2A2. Interacts with REPS2; the interaction is direct (By similarity). Interacts with EPS15; the interaction is direct (By similarity). Interacts with ENTREP1 (By similarity).|||Nucleus|||Phosphorylated on serine and/or threonine residues in mitotic cells. Phosphorylation reduces interaction with REPS2, AP-2 and the membrane fraction. Depolarization of synaptosomes results in dephosphorylation.|||The DPW repeat domain is involved in AP2A2 and clathrin binding.|||The NPF repeat domain is involved in EPS15 binding.|||The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates interaction the AP-2 complex subunit AP2B1.|||Ubiquitinated.|||clathrin-coated pit http://togogenome.org/gene/10090:Cdin1 ^@ http://purl.uniprot.org/uniprot/Q3U4G0 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Nucleus|||Plays a role in erythroid cell differentiation. http://togogenome.org/gene/10090:Pias1 ^@ http://purl.uniprot.org/uniprot/O88907|||http://purl.uniprot.org/uniprot/Q2M4G9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PIAS family.|||Expressed as early as 7.6 dpc. Expression remains high through 15.5 dpc (PubMed:10854042). In 3T3-L1 cells, expression is transiently induced during late adipocyte differentiation (PubMed:24061474).|||Expressed in kidney, heart, spleen, brain and cerebellum; weak expression, if any, in liver and lung.|||Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. In vitro, binds A/T-rich DNA (By similarity). The effects of this transcriptional coregulation, transactivation or silencing, may vary depending upon the biological context. Sumoylates PML (at'Lys-65' and 'Lys-160') and PML-RAR and promotes their ubiquitin-mediated degradation. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 which in turn promotes PML phosphorylation and degradation. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. Plays a dynamic role in adipogenesis by promoting the SUMOylation and degradation of CEBPB (PubMed:24061474). Mediates the nuclear mobility and localization of MSX1 to the nuclear periphery, whereby MSX1 is brought into the proximity of target myoblast differentiation factor genes (PubMed:16600910). Also required for the binding of MSX1 to the core enhancer region in target gene promoter regions, independent of its sumolyation activity (PubMed:16600910). Capable of binding to the core enhancer region TAAT box in the MYOD1 gene promoter (PubMed:16600910).|||Interacts with NR2C1; the interaction promotes its sumoylation. Interacts with DDX21, CSRP2, AXIN1, JUN, SATB2, PLAG1, TP53 and STAT1 (dimer), following IFNA1-stimulation. Interacts with SP3 (preferentially when SUMO-modified). Interacts with KLF8; the interaction results in SUMO ligation and repression of KLF8 transcriptional activity and of its cell cycle progression into G(1) phase (By similarity). Interacts with CHUK/IKKA; this interaction induces PIAS1 phosphorylation. Interacts with PTK2/FAK1; the interaction promotes its sumoylation (By similarity). Interacts with SUMO1, UBE2I, NCOA2 and AR. Interacts with NR2C1; the interaction promotes its sumoylation. Interacts with DDX5. Interacts with MTA1 (By similarity). Interacts with PML (isoform PML-12). Interacts with PRDM1 (By similarity). Interacts (via N-terminus) with MSX1 (via C-terminus); the interaction is required for the localization of both proteins to the nuclear periphery and specific binding of MSX1 to the core enhancer region in target gene promoters (PubMed:16600910).|||Nucleus|||Nucleus speckle|||PML body|||Sumoylated.|||The LXXLL motif is a transcriptional coregulator signature.|||The SP-RING-type domain is required for promoting EKLF sumoylation.|||cytoskeleton http://togogenome.org/gene/10090:Nudt10 ^@ http://purl.uniprot.org/uniprot/P0C027|||http://purl.uniprot.org/uniprot/P0C028 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. DIPP subfamily.|||Binds 3 Mg(2+) or Mn(2+) ions per subunit. Mn(2+) may be the true cofactor in vivo.|||Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate; however, the relevance of such activity in vivo remains unclear.|||Cytoplasm|||Mainly expressed in testis, liver kidney and, at lower level, in heart, brain, spleen, lung and skeletal muscle.|||Nudt10 and Nudt11 code for identical proteins, which gives their indidual characterization difficult. Thus, most experiments do not discriminate between the 2 proteins.|||Predominantly expressed in brain and is weakly or not expressed in other tissues. http://togogenome.org/gene/10090:Eed ^@ http://purl.uniprot.org/uniprot/Q921E6 ^@ Caution|||Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat ESC family.|||Chromosome|||Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By similarity). The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By similarity). Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit (By similarity). Interacts with HDAC, HDAC2, histone H1 and YY1 (By similarity). May interact with ITGA4, ITGAE and ITGB7 (By similarity). Interacts with CDYL (By similarity). Interacts with EZH2. Interacts with KMT2A/MLL1 in adult brain. Interacts with BMAL1.|||Expressed in brain, heart, kidney, liver, lung, muscle, ovary, spleen and testis. Expressed throughout the brain.|||Induced in embryonic stem cells (ES cells) by STAT3 and POU5F1.|||Maternally expressed. Expressed from 5.5 dpc, and expression remains high throughout development. Expression decreases during differentiation of embryonic stem cells (ES cells). Expression increases in prostate during prostate tumor development.|||Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines (By similarity).|||Mice homozygous for a null allele of this protein (Pro-196) exhibit disrupted anterior posterior patterning of the primitive streak during gastrulation and reduced numbers of trophoblast giant cells. Mice homozygous for a hypomorphic allele of this protein (Asn-193) exhibit posterior transformations along the axial skeleton and altered patterns of Hox gene expression.|||Nucleus|||Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark (By similarity). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (By similarity). Genes repressed by the PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. Plays a role in X chromosome inactivation (XCI), in which one of the two X chromosomes in female mammals is transcriptionally silenced to equalize X-linked gene dosage with XY males. Required for stable maintenance of XCI in both embryonic and extraembryonic tissues. May prevent transcriptional activation of facultative heterochromatin during differentiation. Required for development of secondary trophoblast giant cells during placental development. May regulate hippocampal synaptic plasticity in the developing brain.|||The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365 (By similarity).|||Translation initiates from a non-canonical start codon (GUG).|||Was originally thought (PubMed:9234727) to interact with HNRNPK. This apparent interaction may be mediated by the translated product of the 5'-UTR sequence of the 2-hybrid clone. http://togogenome.org/gene/10090:Irx2 ^@ http://purl.uniprot.org/uniprot/P81066 ^@ Caution|||Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TALE/IRO homeobox family.|||Called Irx6 by PubMed:10704856.|||Expressed in specific and overlapping patterns with Irx1 and Irx3 in the developing and adult metanephric kidney. In the adult metanephros, renal expression is found in the loop of Henle in the S3 proximal tubule segment and in the thick ascending limb (TAL) of the distal tubule.|||First expressed at 8.0 dpc. During neural tube closure (8.5 dpc), expression appears for the first time in the rhombencephalon in the presumptive region of future rhombomere 4. During neurogenesis (9.5 dpc to 10.5 dpc), predominantly expressed along the anteroposterior axis of the CNS in the mesencephalon, metencephalon and rhombencephalon. Expression is strong in the tectum of the mesencephalon and in the hindbrain, expression is restricted to rhombomeres. Expression in the spinal cord is weak and confined to the alar plate. Beginning at 9.5 dpc, expressed in the epithelial component of the branchial arches and foregut. At 10.5 dpc, expression extends rostrally into the dorsal diencephalon. Starting at the otic vesicle stage, shows regionalized expression in the developing inner ear with expression in the entire otic vesicle from 10.5 dpc onwards. From 10.5 dpc onwards, weak expression begins in the limb bud. Also expressed in other tissues during organogenesis; at 9.5 dpc, expressed in the superficial ectoderm surrounding the body and in the region of the foregut, which will form the pharynx and the lung bud. at 10.5 dpc, found in the cephalic mesenchyme around the optic vesicle. By 12.5 dpc, still expressed in the mesenchyme, and expression begins in specific subsets of post-mitotic cells in the neuroretina. As development ensues, expression increases in the neuroretina and mesenchymal expression gradually decreases. At 16.5 dpc, expressed exclusively in the inner neuroblast layers of the neuroretina. Expressed in the developing heart in the ventricular septum from the onset of its formation (10.5 dpc) onward. In fetal stages, expression becomes confined to the myocardium of the atrioventricular bundle and bundle branches of the forming ventricular conduction system.|||Nucleus http://togogenome.org/gene/10090:Entpd5 ^@ http://purl.uniprot.org/uniprot/Q3TQC7|||http://purl.uniprot.org/uniprot/Q9WUZ9 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GDA1/CD39 NTPase family.|||Endoplasmic reticulum|||Expressed in response to phosphoinositide 3-kinase (PI3K) signaling. Activation of PI3K results in FOXO phosphorylation by AKT1 and loss of ENTPD5 transcriptional repression. Up-regulated in PTEN-deficient cells.|||Hydrolyzes nucleoside diphosphates with a preference for GDP, IDP and UDP compared to ADP and CDP (PubMed:10369669, PubMed:21074248). In the lumen of the endoplasmic reticulum, hydrolyzes UDP that acts as an end-product feedback inhibitor of the UDP-Glc:glycoprotein glucosyltransferases. UMP can be transported back by an UDP-sugar antiporter to the cytosol where it is consumed to regenerate UDP-glucose (PubMed:21074248). Therefore, it positively regulates protein reglucosylation by clearing UDP from the ER lumen and by promoting the regeneration of UDP-glucose (PubMed:21074248). Protein reglucosylation is essential to proper glycoprotein folding and quality control in the ER (PubMed:21074248).|||Mice display hepatopathy and aspermia. The hepatopathy is progressive and characterized by centrilobular hepatocyte hypertrophy, oval cell proliferation, bile staining of Kupffer cells, and hepatocyte degeneration with increasing incidence and severity of degenerative lesions, development of multiple foci of cellular alteration, and hepatocellular neoplasia with age.|||Monomer; active form. Homodimer; disulfide-linked. Homodimers are enzymatically inactive.|||N-glycosylated; high-mannose type.|||Secreted|||Ubiquitous. http://togogenome.org/gene/10090:Tab2 ^@ http://purl.uniprot.org/uniprot/Q99K90 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF) (By similarity). Acts as an adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains (By similarity). The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1/RIP1 and RIPK2: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7/TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7/TAK1 (PubMed:19927120). Regulates the IL1-mediated translocation of NCOR1 out of the nucleus (PubMed:12150997). Involved in heart development (By similarity).|||Degraded in a lysosome-dependent manner following interaction with TRIM38.|||Endosome membrane|||Interacts with MAP3K7 and TRAF6. Identified in the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2. Binds 'Lys-63'-linked polyubiquitin chains (By similarity). Interacts with NCOR1 and HDAC3 to form a ternary complex (PubMed:12150997). Interacts (via C-terminal) with NUMBL (via PTB domain). Interacts (via the C-terminus) with DYNC2I2 (via WD domains). Interacts with RBCK1. Interacts with TRIM5 (By similarity). Interacts with TRIM38 (via B30.2/SPRY domain), leading to its translocation to lysosomes and degradation (By similarity).|||Lysosome membrane|||Membrane|||Nucleus|||Phosphorylated.|||SUMOylated by TRIM60; leading to inhibition of MAPK/NF-kappaB activation and the innate immune response.|||The RanBP2-type zinc finger (NZF) mediates binding to two consecutive 'Lys-63'-linked ubiquitins.|||Ubiquitinated; following IL1 stimulation or TRAF6 overexpression. Ubiquitination involves RBCK1 leading to proteasomal degradation. Ubiquitinated at Lys-611 by TRIM45 leading to proteasomal degradation.|||Widely expressed.|||cytosol http://togogenome.org/gene/10090:Hipk2 ^@ http://purl.uniprot.org/uniprot/Q9QZR5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15 dpc-17 dpc, mainly in the developing retina, telencephalon and myoblasts. At 12.5 dpc, detected in the developing trigeminal and dorsal root ganglia, and in the developing spinal cord (at protein level). Highly induced during primary fetal liver erythropoiesis. Expressed in the inner retina during late embryogenesis, in nucleus. Highest levels at 14.5 dpc for isoform 2 and P12.5 for isoform 1.|||Autophosphorylation at Tyr-361 in the activation loop activates the kinase and promotes nuclear localization.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.|||Cleaved at Asp-923 and Asp-984 by CASP6 in a p53/TP53-dependent manner. The cleaved form lacks the autoinhibitory C-terminal domain (AID), resulting in a hyperactive kinase, which potentiates p53/TP53 Ser-46 phosphorylation and subsequent activation of the cell death machinery.|||Cytoplasm|||During T-cell activation.|||Inhibited terminal erythroid cell proliferation and terminal enucleation, as well as reduced accumulation of hemoglobin. Impaired transcription of many genes involved in cell proliferation and apoptosis, and of erythroid-specific genes involved in hemoglobin biosynthesis, such as HBA and SLC25A37/MFRN. Enhanced stability of CTNNB1; accumulation of beta-catenin leading to the potentiation of beta-catenin-mediated cell proliferation and tumor formation. Small eyes with deficient lens, abnormal retinal lamination, and thickened retinas.|||Interacts with CREB1, SIAH1, WSB1, CBX4, TRADD, p53/TP53, TP73, TP63, CREBBP, DAXX, P53DINP1, SKI, SMAD1, SMAD2 and SMAD3, but not SMAD4. Interacts with SP100; positively regulates TP53-dependent transcription (By similarity). Interacts with ATF1, PML, RUNX1, EP300, NKX1-2, NKX2-5, UBE2I, HMGA1, CTBP1, AXIN1, NLK, MYB, POU4F1, POU4F2, POU4F3, UBE2I, UBL1 and ZBTB4. Probably part of a complex consisting of p53/TP53, HIPK2 and AXIN1. Interacts with DAZAP2; the interaction results in phosphorylation of DAZAP2 which causes localization of DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent degradation of HIPK2 (By similarity). Interacts with SIAH1; the interaction is promoted by DAZAP2 and results in SIAH1-mediated ubiquitination and subsequent proteasomal degradation of HIPK2 (By similarity).|||Interacts with SPN/CD43 cytoplasmic tail.|||Nucleus|||PML body|||Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (By similarity). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis.|||Sumoylated. When conjugated it is directed to nuclear speckles. Desumoylated by SENP1. Sumoylation on Lys-32 is promoted by the E3 SUMO-protein ligase CBX4 (By similarity).|||Ubiquitinated by FBXO3, WSB1 and SIAH1, leading to rapid proteasome-dependent degradation. The degradation mediated by FBXO3, but not ubiquitination, is prevented in the presence of PML. The degradation mediated by WSB1 and SIAH1 is reversibly reduced upon DNA damage.|||Ubiquitous. Abundant in muscle, heart, small intestine, stomach, kidney and brain; and low in testis, skin and lung. http://togogenome.org/gene/10090:Gltp ^@ http://purl.uniprot.org/uniprot/Q9JL62 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides (By similarity).|||Belongs to the GLTP family.|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Or52e3 ^@ http://purl.uniprot.org/uniprot/Q7TRR4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fosl1 ^@ http://purl.uniprot.org/uniprot/P48755 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. Fos subfamily.|||Heterodimer (By similarity). Interacts with the BAF multiprotein chromatin-remodeling complex subunits SMARCB1 and SMARCD1 (PubMed:29272704). Interacts with ARID1A and JUN (PubMed:29272704).|||Nucleus http://togogenome.org/gene/10090:Pign ^@ http://purl.uniprot.org/uniprot/A0A087WQ32|||http://purl.uniprot.org/uniprot/G3X9F1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGG/PIGN/PIGO family. PIGN subfamily.|||Endoplasmic reticulum membrane|||Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the first alpha-1,4-linked mannose of the glycosylphosphatidylinositol precursor of GPI-anchor.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Or1e29 ^@ http://purl.uniprot.org/uniprot/Q7TRX7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Trap1a ^@ http://purl.uniprot.org/uniprot/P19473 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Nucleus|||P185A and B result from the expression by tumor P815 of a gene that is silent or expressed at a very low level in most if not all normal cells of adult mice. Expressed in testis and mastocytoma. http://togogenome.org/gene/10090:Or6c219 ^@ http://purl.uniprot.org/uniprot/Q8VG46 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5b121 ^@ http://purl.uniprot.org/uniprot/Q7TQQ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ndufb5 ^@ http://purl.uniprot.org/uniprot/D3Z568|||http://purl.uniprot.org/uniprot/Q9CQH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB5 subunit family.|||Complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Slc30a7 ^@ http://purl.uniprot.org/uniprot/Q9JKN1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Cytoplasmic vesicle|||Golgi apparatus membrane|||Highly expressed in liver, spleen, duodenum and part of the jejunum of small intestine (at protein level). Moderately expressed in kidney, lung, and brain. Barely detectable in heart (PubMed:12446736, PubMed:17954933). In brain, expressed in cerebellum, cerebral cortex and hippocampus (at protein level) (PubMed:19283665).|||Homooligomer.|||Homozygous knockout mice are viable, fertile, and display no obvious morphological abnormalities. However, they accumulate less zinc in cells and tissues and have a low body zinc status. This is associated with classic manifestations of dietary zinc deficiency, reduced food intake and poor growth. A decrease in body fat accumulation and reduced zinc absorption in the gut are observed.|||Mitochondrion|||Sarcoplasmic reticulum|||Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway (PubMed:12446736, PubMed:17954933). By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases (By similarity).|||trans-Golgi network http://togogenome.org/gene/10090:Sycp2l ^@ http://purl.uniprot.org/uniprot/A0A0M3U1B0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SYCP2 family.|||Nucleus|||Oocyte-specific protein that localizes to centromeres at the dictyate stage and regulates the survival of primordial oocytes.|||Reduced fertility in females: acceleration of the age-associated decline of fertility in female mice, due to progressive loss of oocytes. Males are normal and fertile.|||Specifically expressed in oocytes.|||centromere http://togogenome.org/gene/10090:Ablim2 ^@ http://purl.uniprot.org/uniprot/E9Q0W6|||http://purl.uniprot.org/uniprot/E9Q4K0|||http://purl.uniprot.org/uniprot/Q8BL65 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15.5 dpc, predominantly expressed in skeletal muscle tissue, including diaphragm, and to a lesser extent in the central nervous system.|||Cytoplasm|||Expressed in brain. Highly expressed in caudate/putamen, moderately expressed in the olfactory bulb. In the hippocampus, expressed in the CA1, CA2 and CA3 fields. In the cerebellum, expressed in Purkinje cells.|||Interacts with F-actin and ABRA.|||May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity. http://togogenome.org/gene/10090:Kif20b ^@ http://purl.uniprot.org/uniprot/Q80WE4 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Expressed in the brain (at protein level) (PubMed:24173802).|||Expressed in the developing brain (PubMed:23864681). Expressed in the apical aspect of the ventricular zone, in the marginal zone, in a narrow stripe between the intermediate zone and the cortical plate at 14.5 dpc (PubMed:23864681). Expressed in multipolar cells at 14 dpc (at protein level) (PubMed:23864681). Expressed in neuronal stem/progenitor cells at 14.5 dpc (PubMed:24173802).|||Midbody|||Nucleus|||Oligomerizes (via kinesin motor domain). Associates with microtubules. Interacts (via C-terminal globular tail region) with PIN1 (via WW domain). Interacts with PRC1 (By similarity). Interacts with SHTN1 (via N-terminus); the interaction is direct and promotes the association of SHTN1 to microtubules in primary neurons (PubMed:23864681). Associates with microtubules (PubMed:23864681).|||Phosphorylated during mitosis by CDK1.|||Plus-end-directed motor enzyme that is required for completion of cytokinesis (By similarity). Required for proper midbody organization and abscission in polarized cortical stem cells (PubMed:24173802). Plays a role in the regulation of neuronal polarization by mediating the transport of specific cargos. Participates in the mobilization of SHTN1 and in the accumulation of PIP3 in the growth cone of primary hippocampal neurons in a tubulin and actin-dependent manner (PubMed:23864681). In the developing telencephalon, cooperates with SHTN1 to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex (PubMed:23864681). Involved in cerebral cortex growth (PubMed:24173802). Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (By similarity).|||axon|||centrosome|||cytoskeleton|||growth cone|||nucleolus|||nucleoplasm|||spindle|||spindle pole http://togogenome.org/gene/10090:Mettl16 ^@ http://purl.uniprot.org/uniprot/Q9CQG2 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ According to a report, N6-methylation of MAT2A affects MAT2A mRNA stability instead of preventing splicing (PubMed:29262316). However, it was later shown that N6-methylation of MAT2A transcripts prevents recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production (By similarity).|||Belongs to the methyltransferase superfamily. METTL16/RlmF family.|||Cytoplasm|||Embryonic lethality: embryos develop until blastocyst stage but development is stopped around the time of implantation (PubMed:30197299). Defects are caused by dysregulation of MAT2A mRNAs (PubMed:30197299).|||Interacts with MEPCE. Interacts with LARP7.|||Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding. Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity. mRNA N6-adenosine-methyltransferase activity is inhibited by zinc.|||Nucleus|||RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:29262316, PubMed:30197299). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (By similarity). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (By similarity). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (By similarity). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:29262316). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (By similarity). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (By similarity). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (By similarity) (PubMed:29262316, PubMed:30197299).|||The K-loop region occludes the S-adenosyl-L-methionine-binding pocket. Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding.|||The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs. The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region. http://togogenome.org/gene/10090:Cars ^@ http://purl.uniprot.org/uniprot/Q9ER72 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Binds 1 zinc ion per subunit.|||Catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys).|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Camk2n1 ^@ http://purl.uniprot.org/uniprot/Q6QWF9 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAMK2N family.|||Expressed in the brain (at protein level) (PubMed:17350603). Expressed in cardiomyocytes but not cardiac fibroblasts (at protein level) (PubMed:33746041).|||Interacts with CAMK2B; the presence of Ca(2+)/calmodulin increases the interaction but is not essential (By similarity). Interacts with CAMK2A; this interaction requires CAMK2A activation by Ca(2+) (By similarity).|||Knockout mice show normal growth rates (PubMed:33746041). Increased expression of inflammatory markers and enhanced recruitment of macrophages to the cardiac infarct border 3 days post-myocardial infarction (MI) (PubMed:33746041). Increased infarct size, interstitial fibrosis, and area of cardiac hypertrophy, leading to decreased left ventricular ejection fractions, fractional shortening and increased spontaneous ventricular arrhythmia at 28 days post MI (PubMed:33746041). Overall survival of mice following MI was significantly decreased (PubMed:33746041). In hippocampal knockdown mice, long-term retrieval-induced memory in response to contextual fear is impaired (PubMed:28642476). Increase in Camk2a T-296 autophosphorylation and Gria1/GluA1 abundance following conditioning and long-term memory retrieval (PubMed:28642476).|||Postsynaptic density|||Potent and specific inhibitor of CaM-kinase II (CAMK2) (By similarity). Plays a role in the maintenance of long-term retrieval-induced memory in response to contextual fear (PubMed:28642476). Modulates blood pressure and vascular reactivity via regulation of CAMK2 activity in addition to regulation of left ventricular mass (By similarity). Mediates the NLRP3 inflammasome in cardiomyocytes via acting as an inhibitor of the MAPK14/p38 and MAPK8/JNK pathways, thereby regulating ventricular remodeling and cardiac rhythm post-myocardial infarction (PubMed:33746041). Negatively effects insulin sensitivity and promotes lipid formation in adipose tissues independent of CAMK2 signaling (PubMed:31327268).|||Synapse|||Up-regulated during retrieval and consolidation of fear memory (PubMed:16819996, PubMed:28642476). Down-regulated in brain during Japanese encephalitis virus (JEV) and rabies virus infection (PubMed:17010311).|||dendrite http://togogenome.org/gene/10090:Slc9a1 ^@ http://purl.uniprot.org/uniprot/Q3UDC9|||http://purl.uniprot.org/uniprot/Q61165 ^@ Activity Regulation|||Caution|||Disease Annotation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated at acidic pHs. Inhibited by cariporide and eniporide. Inhibited by amiloride and 5-amino-substituted derivatives. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) bind and differentially regulate SLC9A1 activity.|||Basolateral cell membrane|||Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Defects in Slc9a1 is the cause of slow-wave epilepsy (swe) phenotype (PubMed:9335342). Mutant mice display slow-wave epilepsy, with a neurological syndrome including ataxia and a unique epilepsy phenotype consisting of 3/sec absence and tonic-clonic seizures. Mutants show selective neuronal death in the cerebellum and brainstem. Mice display also several other significant abnormalities in growth and development, and less than half of the mutant homozygous animals survived to weaning. Most died by 35-40 days (PubMed:9335342).|||Deficient mice exhibit a decreased rate of postnatal growth that is first evident at 2 week of age. At this time, deficient animals also begin to exhibit ataxia and epileptic-like seizures. Approximately 67% of the mutants die before weaning.|||Electroneutral Na(+) /H(+) antiporter that extrudes Na(+) in exchange for external protons driven by the inward sodium ion chemical gradient, protecting cells from acidification that occurs from metabolism (By similarity). Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry (By similarity). Plays a key role in maintening intracellular pH neutral and cell volume, and thus is important for cell growth, proliferation, migration and survival. In addition, can transport lithium Li(+) and functions also as a Na(+)/Li(+) antiporter. SLC9A1 also functions in membrane anchoring and organization of scaffolding complexes that coordinate signaling inputs (By similarity).|||Expressed in kidney, brain and stomach.|||Homodimer; dimerization is crucial for its function (By similarity). Oligomer (By similarity). Interacts with CALM1 in a calcium-dependent manner (By similarity). Interacts with TESC (By similarity). Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium-dependent manner (By similarity). Interacts with CHP2; the interaction occurs in a calcium-dependent manner (By similarity). Interacts with EZR; regulates the cytoskeletal interactions of SLC9A1 and promotes stress fiber formation (By similarity).|||Lateral cell membrane|||Membrane|||O-glycosylated.|||Palmitoylated; may play a major role in SLC9A1 regulation.|||Phosphorylation at Thr-784 increases SLC9A1 activity. Specifically dephosphorylated at Thr-784 by PPP3CA that negatively regulates SLC9A1 activity. Phosphorylation at Ser-652 by AKT1 reduces SLC9A1 binding to CALM1.|||Predicted models used for more than 20 years predicted 10-12 transmembrane segments. Recently, the stucture of SLC9A1 has been solved and reveals that SLC9A1 posseses 13 transmembranes.|||The interacting region with TESC is conflicting: In human, it has been reported that SLC9A1 interacts with TESC via the juxtamembrane region of the cytoplasmic C-terminal domain, including residues 507-549. However, another publication has reported interaction with TESC via residues 637-820, the region of the cytoplasmic C-terminus more distal to the membrane.|||Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1. http://togogenome.org/gene/10090:Myct1 ^@ http://purl.uniprot.org/uniprot/Q8R411 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MYCT1 family.|||Highly expressed in lung, heart, and skeletal muscle. Expressed in brain, eye, liver, kidney, smooth muscle, pancreas, thyroid, thymus, submaxillary gland, spleen, testis, ovary, prostate, epididymis, and uterus. Deregulated expression promotes apoptosis in response to growth factor deprivation. Overexpression in synergy with CCNB1 may promote genomic instability.|||Low levels of expression seen in 7-, 11-, 15- and 17-day embryos.|||May regulate certain MYC target genes, MYC seems to be a direct upstream transcriptional activator. Does not seem to significantly affect growth cell capacity. Overexpression seems to mediate many of the known phenotypic features associated with MYC, including promotion of apoptosis, alteration of morphology, enhancement of anchorage-independent growth, tumorigenic conversion, promotion of genomic instability and inhibition of hematopoietic differentiation.|||Nucleus membrane http://togogenome.org/gene/10090:Or4c107 ^@ http://purl.uniprot.org/uniprot/Q7TR08 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdh15 ^@ http://purl.uniprot.org/uniprot/Q99PJ1 ^@ Developmental Stage|||Disease Annotation|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiparallel heterodimer with CDH23 (PubMed:23135401, PubMed:17805295). Found in a complex with TMIE and LHFPL5 (PubMed:25467981). Interacts with LHFPL5/TMHS; this interaction is required for efficient localization to hair bundles (PubMed:23217710). Interacts with MYO7A (PubMed:16481439). Interacts with USH1G; this interaction may recruit USH1G to the plasma membrane (PubMed:21436032). Interacts with TOMT (PubMed:28504928). Isoforms CD1 and CD3 interact with TMC1 (via N-terminus) and TMC2 (via N-terminus) (PubMed:25114259).|||Cadherin repeats 1 and 2 mediate calcium-dependent heterophilic interaction with CDH23.|||Calcium-dependent cell-adhesion protein. Required for inner ear neuroepithelial cell elaboration and cochlear function. Probably involved in the maintenance of normal retinal function.|||Cell membrane|||Defects in Pcdh15 are the cause of the Ames waltzer (av) phenotype. It is characterized by deafness and a balance disorder, associated with the degeneration of inner ear neuroepithelia.|||Expressed in brain and sensory epithelium of the developing inner ear. Expressed in the retina, in the photoreceptor inner segments, the outer plexiform layer, the inner nuclei layer and the ganglion cell layer and, more diffusely in the inner plexiform layer (at protein level). Not detected in the retinal pigment epithelium (at protein level). Expressed in the spleen, dorsal root ganglion, dorsal aspect of neural tube, floor plate and ependymal cells adjacent to the neural canal.|||Highest level of expression is detected at embryonic day 16. Alternative splicing isoforms have different spatiotemporal expression patterns. In cochlear cultures at the equivalent of postnatal day 3, isoforms belonging to the CD1 (isoforms 1 through 9) and CD3 (isoforms 18 through 20) groups are highly expressed in hair bundles in the basal coils and moderately in those in the middle of the apical coil; they are hardly detectable in those at the apical end of the apical coil (at protein level). At the base of the cultured cochlea, in the more mature hair bundles, CD3 group isoforms are restricted to the tips of the shorter stereocilia in both inner and outer hair cells. By contrast, at the same stage, isoforms belonging to the CD2 group (isoforms 10 through 17) are highly expressed in hair bundles in the apex of the cochlea and, at lower levels, in those in the middle of the apical coil; they are hardly detectable at the base of the cochlea (at protein level). In mature hair bundles, CD1 group isoforms are distributed fairly evenly along most of the length of the stereocilia on auditory hair cells, whereas they are concentrated toward the upper third of the hair bundle in vestibular hair cells. In both the auditory and the vestibular organs, these isoforms are excluded from a region at the very tip of each stereocilium (at protein level). In contrast, CD2 group isoforms are undetectable in adult cochlear hair cells (at protein level). These isoforms are expressed in the entire hair bundle of the immature cells in the sensory epithelium of the early postnatal vestibule and only in the kinocilium in the more mature hair bundles (at protein level). CD3 group isoforms are detected in immature vestibular hair bundles, concentrated toward the tip of each stereocilium, as early as 15.5 dpc. They also localize to the tips of the shorter stereocilia in the mature vestibular hair bundles and are not detected at the tips of the stereocilia in the tallest row (at protein level).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Produced by aberrant splicing sites.|||Secreted|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Mief1 ^@ http://purl.uniprot.org/uniprot/B2RPW2|||http://purl.uniprot.org/uniprot/Q8BGV8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MID49/MID51 family.|||Homodimer. Interacts with DNM1L.|||Membrane|||Mitochondrial outer membrane protein which regulates mitochondrial fission. Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. Regulates DNM1L GTPase activity and DNM1L oligomerization. Binds ADP and can also bind GDP, although with lower affinity. Does not bind CDP, UDP, ATP, AMP or GTP. Inhibits DNM1L GTPase activity in the absence of bound ADP. Requires ADP to stimulate DNM1L GTPase activity and the assembly of DNM1L into long, oligomeric tubules with a spiral pattern, as opposed to the ring-like DNM1L oligomers observed in the absence of bound ADP. Does not require ADP for its function in recruiting DNM1L.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Or5w12 ^@ http://purl.uniprot.org/uniprot/Q7TR42 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or8g54 ^@ http://purl.uniprot.org/uniprot/Q8VG89 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fuz ^@ http://purl.uniprot.org/uniprot/E9QL29|||http://purl.uniprot.org/uniprot/Q3UYI6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fuzzy family.|||Cytoplasm|||Embryonically lethal. Embryos display severe developmental defects, including neural tube closure defects, abnormal patterning of the spinal cord and the limb buds. They display polydactyly on all limbs and defects in skeletal development and organogenesis, including malformed sternum, ribs and long bones, as well as severely hypoplastic lungs and conotruncal defects. The number of hair follicles is also reduced. Defects in ciliogenesis are clearly noticed and result in abnormal hedgehog/smoothened signaling.|||Expressed in dermal and epidermal cells.|||Interacts with CPLANE1. Interacts with INTU and WDPCP; FUZ, INTU and WDPCP probably form the core CPLANE (ciliogenesis and planar polarity effectors) complex.|||Probable planar cell polarity effector involved in cilium biogenesis. May regulate protein and membrane transport to the cilium. Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (PubMed:19877275, PubMed:19767740, PubMed:27158779). May regulate the morphogenesis of hair follicles which depends on functional primary cilia (PubMed:20962855).|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Ccdc97 ^@ http://purl.uniprot.org/uniprot/Q9DBT3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Associates with splicing factor SF3B complex, involved in branch-site recognition.|||May play a role pre-mRNA splicing through the association with the splicing factor SF3B complex which is involved in branch-site recognition.|||Nucleus http://togogenome.org/gene/10090:Phka1 ^@ http://purl.uniprot.org/uniprot/A2AI91|||http://purl.uniprot.org/uniprot/P18826|||http://purl.uniprot.org/uniprot/Q3TQJ0|||http://purl.uniprot.org/uniprot/Q3UV91|||http://purl.uniprot.org/uniprot/Q8CBA7 ^@ Activity Regulation|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.|||Belongs to the phosphorylase b kinase regulatory chain family.|||Both isoforms are expressed in muscle.|||By phosphorylation of various serine residues and by calcium.|||Cell membrane|||Defects in Phka1 are the cause of phosphorylase kinase deficiency in I-strain mice.|||Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin.|||Membrane|||Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.|||Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin. http://togogenome.org/gene/10090:Tlr8 ^@ http://purl.uniprot.org/uniprot/P58682 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by RNAs having enough uridines.|||Belongs to the Toll-like receptor family.|||Endosomal receptor that plays a key role in innate and adaptive immunity. Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2. Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction. In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively.|||Endosome membrane|||Homodimer (By similarity). Interacts with MYD88 via their respective TIR domains (Probable). Interacts with UNC93B1 (PubMed:19451267). Interacts with BTK (By similarity). Interacts with SMPDL3B (PubMed:26095358).|||Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins. The cleavage is necessary for dimer formation and subsequent activation.|||Ubiquitinated by RNF216; leading to degradation by the proteasome. http://togogenome.org/gene/10090:Cnbp ^@ http://purl.uniprot.org/uniprot/P53996 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Arginine methylation by PRMT1 in the Arg/Gly-rich region impedes RNA binding.|||Associates with the 40S ribosomal subunit, the 80S ribosome and with polysomes.|||Cytoplasm|||Endoplasmic reticulum|||Expressed from pre-gastrulation to organogenesis stages (at protein level) (PubMed:12706888). At this stage 7.5 dpc, expression becomes asymmetrical and localizes to all three germ layer regions of the anterior conceptus, suggesting a possible role in anterior-posterior axis patterning (at protein level) (PubMed:12706888). Later expressed in the forebrain (9 dpc and 10 dpc) and in the midbrain (11.5 dpc) (at protein level) (PubMed:12706888). From 9 dpc to 11.5 dpc, expressed in the early craniofacial structures, limb buds and somites (at protein level) (PubMed:12706888). Highest expression is in the face and includes the cranial and caudal regions of the mandibular prominences, the budding maxillary prominences and the roof of the stomodeum (at protein level) (PubMed:12706888). Before gastrulation, 5.5 dpc, expression is initially symmetric and uniform in the epiblast and in the extra-embryonic visceral endoderm (PubMed:7896269).|||Nucleus|||Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5'-GTGCGGTG-3', and thereby mediates transcriptional repression (By similarity). Has a role as transactivator of the Myc promoter (PubMed:12706888). Binds single-stranded RNA in a sequence-specific manner (By similarity). Binds G-rich elements in target mRNA coding sequences (By similarity). Prevents G-quadruplex structure formation in vitro, suggesting a role in supporting translation by resolving stable structures on mRNAs (By similarity). http://togogenome.org/gene/10090:Tas1r2 ^@ http://purl.uniprot.org/uniprot/Q925I4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family. TAS1R subfamily.|||Cell membrane|||Expressed mainly in circumvallate and foliate taste papillae.|||Forms heterodimers with TAS1R3.|||Putative taste receptor. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners. http://togogenome.org/gene/10090:Isoc2b ^@ http://purl.uniprot.org/uniprot/Q9DCC7 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the isochorismatase family.|||Cytoplasm|||Interacts with CDKN2A.|||Nucleus|||Ubiquitous. Expressed predominantly in uterus, stomach and urinary tract. http://togogenome.org/gene/10090:Dctn5 ^@ http://purl.uniprot.org/uniprot/Q9QZB9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynactin subunits 5/6 family. Dynactin subunit 5 subfamily.|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.|||Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. Within the complex DCTN6 forms a heterodimer with DCTN5 (PubMed:10525537). The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity).|||cytoskeleton|||kinetochore http://togogenome.org/gene/10090:Ift56 ^@ http://purl.uniprot.org/uniprot/Q8BS45 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT56 family.|||Component of the IFT complex B. Interacts with IFT46; the interaction is direct.|||Component of the intraflagellar transport (IFT) complex B required for transport of proteins in the motile cilium. Required for transport of specific ciliary cargo proteins related to motility, while it is neither required for IFT complex B assembly or motion nor for cilium assembly. Required for efficient coupling between the accumulation of GLI2 and GLI3 at the ciliary tips and their dissociation from the negative regulator SUFU (PubMed:22718903, PubMed:25340710). Plays a key role in maintaining the integrity of the IFT complex B and the proper ciliary localization of the IFT complex B components. Not required for IFT complex A ciliary localization or function. Essential for maintaining proper microtubule organization within the ciliary axoneme (PubMed:28264835).|||Expressed during early development stages (12.5 dpc, 13.5 dpc, and 14.5 dpc).|||High expression detected in testis. Detected also retina, kidney, lung and brain tissue. The expression level is low in spleen (PubMed:22718903). Expressed in the developing liver (PubMed:31595528). Present in the airway epithelial cells and the testes (at protein level) (PubMed:25340710).|||Partial embryonic lethality and patterning defects. Surviving mice show hopping gait, polydactyly, hydrocephalus, and male sterility. Impaired hedgehog signaling. Primary cilia are not reduced in number and their length is normal (PubMed:25340710). Mice exhibit defective cilia structure, including abnormal positioning and number of ciliary microtubule doublets, abnormal localization of IFT complex B components and significantly reduced ciliary tip accumulation of proteins GLI2 and GLI3 (PubMed:28264835).|||cilium http://togogenome.org/gene/10090:Fxr1 ^@ http://purl.uniprot.org/uniprot/A0A0G2JEP0|||http://purl.uniprot.org/uniprot/Q61584 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FMR1 family.|||Cytoplasm|||Cytoplasmic ribonucleoprotein granule|||Death shortly after birth (PubMed:15128702). Mice expressing low levels of Fxr1 show postnatal growth retardation with reduced increase in muscle mass and strength (PubMed:15128702). They die within 3 weeks of birth (PubMed:15128702). Conditional deletion in macrophages leads to enhanced Tumor necrosis factor (TNF) production (PubMed:15548538). Conditional deletion in excitatory neurons in the forebrain of early postnatal mice enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation: defects are caused by de novo GRIA2/GluA2 synthesis (PubMed:25456134). Conditional deletion in adult neural stem cells results in fewer adult-born cells in the dentate gyrus, reducing populations across different stages of neurogenesis, including radial glia-like cells, intermediate progenitors, neuroblasts, immature neurons and neurons (PubMed:28204491). Conditional deletion in germline cells leads to male infertility: defects are caused by impaired translation of a subset of transcripts in adult mouse testes (PubMed:35951695).|||Disordered region at the C-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that stores mRNAs.|||In early embryogenesis, highest expression in somites and central nervous system (PubMed:10409431, PubMed:16000371). Also expressed in spinal cord, surrounding mesenchymal tissue and undifferentiated gonad (PubMed:10409431). In mid-embryogenesis, most prominent in gonad and muscle tissue (PubMed:10409431). Also expressed in liver, retina, telencephalon and mesencephalon (PubMed:10409431). In late embryogenesis, restricted to skeletal muscle and proliferative active layers of brain (PubMed:10409431). After birth, highly expressed in postmeiotic spermatids (at protein level) (PubMed:10409431, PubMed:35951695). Expressed in neurons of the developing hippocampus (PubMed:22022532). Expressed in new cells generated in the adult dentate gyrus throughout the progression of adult neurogenesis (PubMed:28204491). Intermediate levels are found in heart, liver and kidney with lower levels in brain and skeletal muscle (PubMed:10409431). Isoform(s) containing the 27 amino acid pocket (residues 564-590) are present in adult heart and muscle (PubMed:10409431, PubMed:32328638).|||Interacts with FMR1 (By similarity). Interacts with FRX2 (By similarity). Interacts with TDRD3 (By similarity). Interacts with HABP4 (By similarity). Interacts with CYFIP2 but not with CYFIP1 (PubMed:11438699). Interacts with EIF4G3; promoting translation of target mRNAs (PubMed:35951695). Interacts with ELAVL1 (By similarity). Interacts with CEP63; inhibiting 'Lys-63'-linked ubiquitination (By similarity).|||Nucleus envelope|||Phosphorylation at Ser-449 by PAK1 promotes its relocalization to stress granules and activity (By similarity). Phosphorylated by MAPK1/ERK2, promoting subsequent phosphorylation by GSK3B (PubMed:26240334). Phosphorylated by GSK3B, promoting ubiquitination and degradation by the proteasome (PubMed:26240334, PubMed:29142209, PubMed:32893934).|||Postsynapse|||Present in adult heart and muscle.|||Stress granule|||Synapse|||The tandem Agenet-like domains preferentially recognize trimethylated histone peptides.|||Ubiquitinated by the SCF(FBXO4) complex, leading to its degradation by the proteasome: ubiquitination by the SCF(FBXO4) complex takes place following phosphorylation by GSK3B (PubMed:29142209, PubMed:32893934, PubMed:26240334). Ubiquitinated and degraded in a GSK3B-dependent manner in during both scaling and sleep deprivation (PubMed:32893934). Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its degradation: interaction with CEP63 inhibits 'Lys-63'-linked ubiquitination (By similarity).|||axon|||dendrite|||dendritic spine|||mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis (PubMed:15128702, PubMed:25456134, PubMed:32328638, PubMed:35951695). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:25456134). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:32328638, PubMed:35951695). Required to activate translation of stored mRNAs during late spermatogenesis: acts by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules that recruit translation initiation factor EIF4G3 to activate translation of stored mRNAs in late spermatids (PubMed:35951695). Promotes translation of MYC transcripts by recruiting the eIF4F complex to the translation start site (By similarity). Acts as a negative regulator of inflammation in response to IL19 by promoting destabilization of pro-inflammatory transcripts (By similarity). Also acts as an inhibitor of inflammation by binding to TNF mRNA, decreasing TNF protein production (PubMed:15548538). Acts as a negative regulator of AMPA receptor GRIA2/GluA2 synthesis during long-lasting synaptic potentiation of hippocampal neurons by binding to GRIA2/GluA2 mRNA, thereby inhibiting its translation (PubMed:25456134). Regulates proliferation of adult neural stem cells by binding to CDKN1A mRNA and promoting its expression (PubMed:28204491). Acts as a regulator of sleep and synaptic homeostasis by regulating translation of transcripts in neurons (PubMed:32893934). Required for embryonic and postnatal development of muscle tissue by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules (PubMed:15128702, PubMed:32328638). Involved in the nuclear pore complex localization to the nuclear envelope by preventing cytoplasmic aggregation of nucleoporins: acts by preventing ectopic phase separation of nucleoporins in the cytoplasm via a microtubule-dependent mechanism (By similarity). http://togogenome.org/gene/10090:Rela ^@ http://purl.uniprot.org/uniprot/Q04207 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-c-Rel complex. Homodimer; component of the NF-kappa-B p65-p65 complex. Component of the NF-kappa-B p65-p52 complex. May interact with ETHE1. Binds TLE5 and TLE1. Interacts with TP53BP2. Binds to and is phosphorylated by the activated form of either RPS6KA4 or RPS6KA5. Interacts with ING4 and this interaction may be indirect. Interacts with CARM1, USP48 and UNC5CL. Interacts with IRAK1BP1. Interacts with NFKBIA. Interacts with GSK3B. Interacts with NFKBIB. Interacts with NFKBIE. Interacts with NFKBIZ. Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14. Interacts with HDAC3; HDAC3 mediates the deacetylation of RELA. Interacts with HDAC1; the interaction requires non-phosphorylated RELA. Interacts with CBP; the interaction requires phosphorylated RELA. Interacts (phosphorylated at 'Thr-254') with PIN1; the interaction inhibits p65 binding to NFKBIA. Interacts with SOCS1. Interacts with MTDH and PHF11. Interacts with NFKBID. Interacts with ARRB2. Interacts with NFKBIA (when phosphorylated), the interaction is direct; phosphorylated NFKBIA is associated with a SCF(BTRC)-like complex lacking CUL1. Interacts with RNF25. Interacts (via C-terminus) with DDX1 (By similarity). Interacts with UFL1 and COMMD1 (By similarity). Interacts with BRMS1; this promotes deacetylation of 'Lys-310'. Interacts (when acetylated at Lys-310) with BRD4; leading to activation of the NF-kappa-B pathway (By similarity). Interacts with EHMT1 (via ANK repeats). Interacts with NOTCH2. Directly interacts with MEN1; this interaction represses NFKB-mediated transactivation (By similarity). Interacts with AKIP1, which promotes the phosphorylation and nuclear retention of RELA (By similarity). Interacts (via the RHD) with GFI1; the interaction, after bacterial lipopolysaccharide (LPS) stimulation, inhibits the transcriptional activity by interfering with the DNA-binding activity to target gene promoter DNA. Interacts with MEFV (By similarity). Interacts with CLOCK. Interacts with FOXP3 (By similarity). Interacts (via N-terminus) with CPEN1; this interaction induces proteolytic cleavage of p65/RELA subunit and inhibition of NF-kappa-B transcriptional activity (By similarity). Interacts with CDK5RAP3; stimulates the interaction of RELA with HDAC1, HDAC2 and HDAC3 thereby inhibiting NF-kappa-B transcriptional activity (By similarity). Interacts with DHX9; this interaction is direct and activates NF-kappa-B-mediated transcription (By similarity). Interacts with TBX21 (PubMed:23616576). Interacts with LRRC25 (By similarity). Interacts with KAT2A (PubMed:25024434). Interacts (via transcriptional activation domain 3) with ZBTB7A; involved in the control by RELA of the accessibility of target gene promoters (PubMed:29813070). Directly interacts with DDX3X; this interaction may trap RELA in the cytoplasm, impairing nuclear relocalization upon TNF activating signals (By similarity). Interacts with PHF2 (PubMed:22921934). Interacts with MKRN2; the interaction leads to its polyubiquitination and proteasome-dependent degradation (PubMed:28378844). Interacts with ECSIT (By similarity).|||Cytoplasm|||Monomethylated at Lys-310 by SETD6. Monomethylation at Lys-310 is recognized by the ANK repeats of EHMT1 and promotes the formation of repressed chromatin at target genes, leading to down-regulation of NF-kappa-B transcription factor activity. Phosphorylation at Ser-311 disrupts the interaction with EHMT1 without preventing monomethylation at Lys-310 and relieves the repression of target genes.|||NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression (PubMed:29813070). Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (By similarity). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression (By similarity).|||Nucleus|||Phosphorylation on Ser-534 stimulates acetylation on Lys-310 and interaction with CBP; the phosphorylated and acetylated forms show enhanced transcriptional activity (By similarity). Phosphorylation at Ser-311 disrupts the interaction with EHMT1 and promotes transcription factor activity. Phosphorylation at Ser-276 by RPS6KA4 and RPS6KA5 promotes its transactivation and transcriptional activities.|||Proteolytically cleaved within a conserved N-terminus region required for base-specific contact with DNA in a CPEN1-mediated manner, and hence inhibits NF-kappa-B transcriptional activity.|||RELA haploinsufficient mice show cutaneous ulceration, epidermal skin loss and a predominance of neutrophils and macrophages in the dermis and hypodermis in response to TNF treatment.|||Reversibly acetylated; the acetylation seems to be mediated by CBP, the deacetylation by HDAC3 and SIRT2. Acetylation at Lys-122 enhances DNA binding and impairs association with NFKBIA. Acetylation at Lys-310 is required for full transcriptional activity in the absence of effects on DNA binding and NFKBIA association. Acetylation at Lys-310 promotes interaction with BRD4. Acetylation can also lower DNA-binding and results in nuclear export. Interaction with BRMS1 promotes deacetylation of Lys-310. Lys-310 is deacetylated by SIRT2 (By similarity).|||S-nitrosylation of Cys-38 inactivates the enzyme activity.|||Sulfhydration at Cys-38 mediates the anti-apoptotic activity by promoting the interaction with RPS3 and activating the transcription factor activity.|||Sumoylation by PIAS3 negatively regulates DNA-bound activated NF-kappa-B.|||The transcriptional activation domain 1/TA1 and the transcriptional activation domain 2/TA2 have direct transcriptional activation properties (PubMed:29813070). The 9aaTAD motif found within the transcriptional activation domain 2 is a conserved motif present in a large number of transcription factors that is required for their transcriptional transactivation activity (By similarity).|||The transcriptional activation domain 3/TA3 does not participate in the direct transcriptional activity of RELA but is involved in the control by RELA of the accessibility of target gene promoters. Mediates interaction with ZBTB7A.|||Ubiquitinated by MKRN2, leading to its proteasomal degradation (PubMed:28378844). Degradation is required for termination of NF-kappa-B response (By similarity). Polyubiquitinated via 'Lys-29'-linked ubiquitin; leading to lysosomal degradation (By similarity). http://togogenome.org/gene/10090:Zfand1 ^@ http://purl.uniprot.org/uniprot/Q8BFR6 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Associates with the 26S proteasome; this association occurs upon exposure to arsenite and is reduced in the presence of ATP. Interacts (via AN1-type 1 and 2 zinc fingers) with PSMD1; this interaction is increased upon arsenite treatment and occurs in an ATP-independent manner. Interacts with PSMC4. Interacts with PSMA1. Interacts (via its ubiquitin-like region) with VCP; this interaction occurs in an arsenite-dependent manner and is necessary for the recruitment of the ubiquitin-selective ATPase VCP to stress granules (SGs).|||Plays a role in the regulation of cytoplasmic stress granules (SGs) turnover. SGs are dynamic and transient cytoplasmic ribonucleoprotein assemblies important for cellular protein homeostasis when protein production is suspended after acute exogenous stress. Associates with SGs and is involved in the efficient and specific arsenite-induced clearance process of SGs through the recruitment of the ubiquitin-selective ATPase VCP and the 26S proteasome. This process requires both complexes for efficient degradation of damaged ubiquitinated SG proteins during recovery from arsenite stress, and hence avoiding aberrant cytoplasmic SGs degradation via autophagy.|||Stress granule|||The ubiquitin-like region is necessary for its localization to stress granules (SGs) in a VCP-independent manner. The AN1-type 1 and 2 zinc finger domains are necessary for the recruitment of the 26S proteasome to SGs. Both the AN1-type 1 and 2 zinc finger domains and the ubiquitin-like region are necessary for efficient SGs clearance upon specific arsenite-induced responses. http://togogenome.org/gene/10090:Spsb1 ^@ http://purl.uniprot.org/uniprot/Q9D5L7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPSB family.|||Component of the probable ECS(SPSB1) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB1 (By similarity). Interacts with CUL5, RNF7, ELOB and ELOC (By similarity). Directly interacts with MET tyrosine kinase domain in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction (PubMed:16369487). When phosphorylated, interacts with RASA1 without affecting its stability (By similarity). Interacts (via B30.2/SPRY domain) with PAWR; this interaction is direct and occurs in association with the Elongin BC complex (PubMed:16369487, PubMed:16498413, PubMed:20561531).Interacts with EPHB2 (By similarity). Interacts with NOS2 (PubMed:20603330).|||Cytoplasm|||Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (By similarity). Acts as a bridge which links the NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By similarity).|||The B30.2/SPRY domain is involved in MET and PAWR binding.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (By similarity).|||cytosol http://togogenome.org/gene/10090:Acad8 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0P1|||http://purl.uniprot.org/uniprot/Q9D7B6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acyl-CoA dehydrogenase family.|||Homotetramer, formed by a dimer of dimers.|||Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway. To a lesser extent, also able to catalyze the oxidation of (2S)-2-methylbutanoyl-CoA.|||Mitochondrion http://togogenome.org/gene/10090:Mif4gd ^@ http://purl.uniprot.org/uniprot/Q3UBZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MIF4GD family.|||Cytoplasm|||Functions in replication-dependent translation of histone mRNAs which differ from other eukaryotic mRNAs in that they do not end with a poly-A tail but a stem-loop. May participate in circularizing those mRNAs specifically enhancing their translation (By similarity).|||Interacts with EIF4G1, EIF4G2 and SLBP; probably tethered by SLBP to the 3'-end of mRNAs ending with the histone stem-loop, it also interacts with EIF4G1 which is bound to their 5'-end.|||Nucleus http://togogenome.org/gene/10090:Or10ak8 ^@ http://purl.uniprot.org/uniprot/L7MTV4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Cdc25c ^@ http://purl.uniprot.org/uniprot/P48967|||http://purl.uniprot.org/uniprot/Q3UR74 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MPI phosphatase family.|||Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.|||Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle. Directly dephosphorylates CDK1 and activates its kinase activity. When phosphorylated, highly effective in activating G2 cells into prophase (By similarity). May be involved in regulating the proliferation of T-lymphocytes following cytokine stimulation.|||Interacts with MAPK14 and 14-3-3 proteins (By similarity). When phosphorylated at Ser-128 and/or Thr-129, interacts with PLK1 (By similarity). Interacts with MARK3/C-TAK1 (By similarity).|||Nucleus|||Phosphorylated by PLK4. Phosphorylated by PLK1, leading to activate the phosphatase activity (By similarity). Phosphorylated by CHEK1 and MAPKAPK2. This phosphorylation creates a binding site for 14-3-3 protein and inhibits the phosphatase activity. Phosphorylation by PLK3 at Ser-213 promotes nuclear translocation. Ser-220 is a minor phosphorylation site (By similarity). Phosphorylation by CDK1 occurs at G2 and G2-M transition and leads to increased activity (By similarity).|||Spleen and thymus. http://togogenome.org/gene/10090:Tex28 ^@ http://purl.uniprot.org/uniprot/B1AYN9 ^@ Similarity ^@ Belongs to the TEX28 family. http://togogenome.org/gene/10090:Zfp449 ^@ http://purl.uniprot.org/uniprot/Q8CB76 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Lrp2bp ^@ http://purl.uniprot.org/uniprot/Q9D4C6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with LRP2.|||May act as an adapter that regulates LRP2 function. http://togogenome.org/gene/10090:Kat14 ^@ http://purl.uniprot.org/uniprot/Q8CID0 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. May function as a scaffold for the ATAC complex to promote ATAC complex stability. Has also weak histone acetyltransferase activity toward histone H4. Required for the normal progression through G1 and G2/M phases of the cell cycle (By similarity).|||Cytoplasm|||Early embryonic lethality. Severe growth retardation, increased apoptosis, and alterations in the cell cycle.|||Interacts with the LIM 1 domain of CSRP2. Component of the ADA2A-containing complex (ATAC), composed of CSRP2BP, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1. In the complex, it probably interacts directly with KAT2A, MBIP and WDR5.|||Nucleus http://togogenome.org/gene/10090:Ehhadh ^@ http://purl.uniprot.org/uniprot/Q9DBM2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated, leading to enhanced enzyme activity. Acetylation is enhanced by up to 80% after treatment either with trichostin A (TCA) or with nicotinamide (NAM) with highest increase on Lys-344. Acetylation and enzyme activity increased by about 1.5% on addition of fatty acids (By similarity).|||Enzyme activity enhanced by acetylation.|||In the C-terminal section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.|||In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.|||Monomer.|||Mutant mice fed a normal chow are phenotypically indistinguishable from wild-types. Mutant mice fed coconut oil rapidly lose weight and most of them die within 3 weeks. They overaccumulate dicarboxylic fatty acids, which activate all fatty acid oxidation pathways and lead to liver inflammation, fibrosis, and death.|||Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-CoA isomerase activities. Catalyzes two of the four reactions of the long chain fatty acids peroxisomal beta-oxidation pathway (PubMed:17442273, PubMed:24075987). Can also use branched-chain fatty acids such as 2-methyl-2E-butenoyl-CoA as a substrate, which is hydrated into (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA (By similarity). Optimal isomerase for 2,5 double bonds into 3,5 form isomerization in a range of enoyl-CoA species. Also able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species (By similarity). With HSD17B4, catalyzes the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity (Probable). Regulates the amount of medium-chain dicarboxylic fatty acids which are essential regulators of all fatty acid oxidation pathways (PubMed:24075987). Also involved in the degradation of long-chain dicarboxylic acids through peroxisomal beta-oxidation (By similarity).|||Peroxisome http://togogenome.org/gene/10090:Pfdn2 ^@ http://purl.uniprot.org/uniprot/O70591 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the prefoldin subunit beta family.|||Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.|||Cytoplasm|||Heterohexamer of two PFD-alpha type and four PFD-beta type subunits. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with URI1; the interaction is phosphorylation-dependent and occurs in a growth-dependent manner.|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:Tmc2 ^@ http://purl.uniprot.org/uniprot/Q8R4P4 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMC family.|||Cell membrane|||Expressed at low, constant levels in temporal bone from embryonic day 14 to day 1 after birth. Increases by 8 to 16-fold at day 5, 10 and 20.|||Inner ear and testis.|||Interacts with TOMT. The interaction of TMC1 and TMC2 with TOMT is required for the transportation of TMC1/2 into the stereocilia of hair cells (PubMed:28504928). Interacts (via N-terminus) with both isoforms CD1 and CD3 of PCDH15 (PubMed:25114259). Interacts with CIB2 (PubMed:28663585).|||Probable ion channel required for the normal function of cochlear hair cells (By similarity). Component of the hair cell's mechanotransduction (MET) machinery. Involved in mechanosensitive responses of the hair cells (By similarity). http://togogenome.org/gene/10090:Zfp523 ^@ http://purl.uniprot.org/uniprot/Q8BMU0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Rtn3 ^@ http://purl.uniprot.org/uniprot/Q9ES97 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Homodimer. Interacts with RTN4. Isoform 3 interacts with BACE1, BACE2, BCL2 and FADD (By similarity). Interacts with ATL1 and ATL2 (PubMed:19665976). Isoform 3 interacts with TMEM33 (PubMed:25612671). Interacts with ZFYVE27 and with KIF5A in a ZFYVE27-dependent manner (By similarity). Interacts with RIGI (By similarity). Interacts with TRIM25 (By similarity).|||Isoform 1, isoform 3, isoform 4 and isoform 5 are expressed in spinal cord. Isoform 1 is present in brain, where it is expressed in the neurons of cerebral cortex, hippocampus, hypothalamus and cerebellum (at protein level).|||May be involved in membrane trafficking in the early secretory pathway. Inhibits BACE1 activity and amyloid precursor protein processing. May induce caspase-8 cascade and apoptosis. May favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress (PubMed:24262037). Induces the formation of endoplasmic reticulum tubules. Acts also as an inflammation-resolving regulator by interacting with both TRIM25 and RIGI, subsequently impairing RIGI 'Lys-63'-linked polyubiquitination leading to IRF3 and NF-kappa-B inhibition (By similarity). http://togogenome.org/gene/10090:Trpc5 ^@ http://purl.uniprot.org/uniprot/Q2KHN9|||http://purl.uniprot.org/uniprot/Q8C8A8|||http://purl.uniprot.org/uniprot/Q9QX29 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC5 sub-subfamily.|||Calcium channel activity is enhanced by MYLK, that promotes its subcellular localization at the plasma membrane.|||Cell membrane|||Expressed almost exclusively in brain, in mitral cells of the olfactory bulb, in lateral cerebellar nuclei and in pyramidal neurons of the hippocampus. Very low levels detected in liver kidney, testis, and uterus.|||Homotetramer and heterotetramer with TRPC1 and/or TRPC4 (By similarity). Interacts (via C-terminus) with CABP1 (PubMed:15895247). Interacts with SLC9A3R1/NHERF (PubMed:10980202). Interacts with MX1 and RNF24 (By similarity). Interacts with SESTD1 (via the spectrin 1 repeat) (By similarity). Interacts with TRPC4AP (PubMed:20458742). Interacts with PLSCR1 (PubMed:32110987).|||Membrane|||Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Has also been shown to be calcium-selective. May also be activated by intracellular calcium store depletion (By similarity). Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with PLSCR1 (PubMed:32110987). http://togogenome.org/gene/10090:Ceacam15 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1L0 ^@ Similarity|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. CEA family.|||Detected in placenta. http://togogenome.org/gene/10090:Npr1 ^@ http://purl.uniprot.org/uniprot/P18293|||http://purl.uniprot.org/uniprot/Q2TAY4|||http://purl.uniprot.org/uniprot/Q3UY30 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Homodimer.|||Membrane|||Mice display systemic hypertension associated with cardiac hypertrophy and ventricular enlargement.|||Phosphorylation of the protein kinase-like domain is required for full activation by ANP.|||Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand. http://togogenome.org/gene/10090:Cst10 ^@ http://purl.uniprot.org/uniprot/Q9JM84 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cystatin family.|||By high phosphate diet.|||In cartilage, expressed mainly in mature chondrocytes including prehypertrophic and hypertrophic cells (at protein level) (PubMed:13679380). Expressed exclusively in cartilage (PubMed:11856874).|||In maturing chondrocytes, expression appears at day 3 and increases thereafter.|||May play a role in the last steps of the chondrocyte differentiation pathway as an inducer of maturation (PubMed:13679380). Induces chondrocyte calcification during endochondral ossification by playing a role in the transcriptional inhibition of ENPP1, a generator of pyrophosphate which inhibits calcification (PubMed:16680148). Possibly impairs the binding of a transcription factor to the ENPP1 promoter (PubMed:16680148). Unlike other cystatins, does not have thiol protease inhibitor activity (PubMed:16680148).|||No visible phenotype. Microscopic decrease in the calcification of hypertrophic chondrocytes at the growth plate.|||cytosol http://togogenome.org/gene/10090:Atg4a ^@ http://purl.uniprot.org/uniprot/Q5EBK1|||http://purl.uniprot.org/uniprot/Q8C9S8 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C54 family.|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.|||Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins to reveal a C-terminal glycine. Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy. Preferred substrate is GABARAPL2 followed by MAP1LC3A and GABARAP. Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3. In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy. Compared to ATG4B, the major protein for proteolytic activation of ATG8 proteins, shows weaker ability to cleave the C-terminal amino acid of ATG8 proteins, while it displays stronger delipidation activity. Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy.|||Cytoplasm|||Inhibited by N-ethylmaleimide. Redox-regulated during autophagy since reducing conditions activate ATG4A whereas an oxidizing environment such as the presence of H(2)O(2) inhibits its activity.|||Interacts with ATG9A; the interaction is direct.|||The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins. Required for proteolytic activation and delipidation of ATG8 proteins. http://togogenome.org/gene/10090:Tdp2 ^@ http://purl.uniprot.org/uniprot/Q9JJX7 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCR4/nocturin family.|||Binds 1 magnesium or manganese ion per subunit.|||Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity.|||Cytoplasm|||DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (PubMed:23104055, PubMed:24808172, PubMed:27099339, PubMed:27060144). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2 (PubMed:22740648). Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. Acts as a regulator of ribosome biogenesis following stress (By similarity).|||Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4.|||Nucleus|||PML body|||Ubiquitinated by TRAF6.|||Widely expressed (PubMed:10764746). Expressed in whole brain, cerebellum, quiescent cortical astrocytes and cerebellar granule neurons (PubMed:24658003).|||nucleolus http://togogenome.org/gene/10090:Zscan22 ^@ http://purl.uniprot.org/uniprot/Q8BGS5|||http://purl.uniprot.org/uniprot/Q8C5G3 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pyroxd1 ^@ http://purl.uniprot.org/uniprot/Q3TMV7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. PYROXD1 subfamily.|||Binds 1 FAD per subunit.|||Cytoplasm|||Nucleus|||Probable FAD-dependent oxidoreductase; involved in the cellular oxidative stress response (By similarity). Required for normal sarcomere structure and muscle fiber integrity (By similarity).|||sarcomere http://togogenome.org/gene/10090:Rnf182 ^@ http://purl.uniprot.org/uniprot/Q8C432 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||E3 ubiquitin-protein ligase that mediates the ubiquitination of ATP6V0C and targets it to degradation via the ubiquitin-proteasome pathway. Also plays a role in the inhibition of TLR-triggered innate immune response by mediating 'Lys'-48-linked ubiquitination and subsequent degradation of NF-kappa-B component RELA.|||Expressed in the cortex, hippocampus, cerebellum and spinal cord, but not in the heart, liver, kidney or skeletal muscle.|||Interacts with ATP6V0C.|||Membrane|||The RING-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Pdgfd ^@ http://purl.uniprot.org/uniprot/Q925I7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by proteolytic cleavage. Proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor-binding epitopes of the core domain. Cleavage after Arg-247 or Arg-249 by urokinase plasminogen activator gives rise to the active form (By similarity).|||Belongs to the PDGF/VEGF growth factor family.|||Expressed at high levels in developing heart, lung, kidney and some muscle derivatives. Moderately expressed in liver, brain and testis. In the kidney, localized to glomerular mesangial cells and vascular smooth muscle cells. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, expressed in interstitial cells at day 4, with an increased to maximal expression at day 14.|||Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Plays an important role in wound healing (By similarity). Has oncogenic potential and can induce tumor formation. Induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Can initiate events that lead to a mesangial proliferative glomerulonephritis, including influx of monocytes and macrophages and production of extracellular matrix.|||Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB (By similarity).|||Secreted http://togogenome.org/gene/10090:Arhgap33 ^@ http://purl.uniprot.org/uniprot/A0A140LHW2|||http://purl.uniprot.org/uniprot/Q3UQS4|||http://purl.uniprot.org/uniprot/Q80YF9 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PX domain-containing GAP family.|||Cell membrane|||Dramatically induced during adipocyte differentiation.|||Highly expressed in brain and testis. Also expressed in white adipose tissue (WAT) and muscle at a low level.|||May be involved in several stages of intracellular trafficking (By similarity). Could play an important role in the regulation of glucose transport by insulin. May act as a downstream effector of RHOQ/TC10 in the regulation of insulin-stimulated glucose transport.|||Specifically interacts with CDC42 and RHOQ/TC10 through its Rho-GAP domain. Interacts with NEK6 (By similarity).|||The N-terminal PX domain interacts specifically with phosphatidylinositol 4,5-bisphosphate. http://togogenome.org/gene/10090:Ccl3 ^@ http://purl.uniprot.org/uniprot/P10855|||http://purl.uniprot.org/uniprot/Q5QNW0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Expressed in lung, spleen, and pancreas.|||Monokine with inflammatory, pyrogenic and chemokinetic properties. Has a potent chemotactic activity for eosinophils. Binding to a high-affinity receptor activates calcium release in neutrophils.|||Secreted http://togogenome.org/gene/10090:Nepn ^@ http://purl.uniprot.org/uniprot/Q9CQ76 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family.|||Detected in the definitive endoderm from 7.5 dpc onwards (PubMed:17683524). Strongly expressed in the developing midgut by 9 dpc, but then at 9.5 dpc expression appears to decrease (PubMed:17683524). Global expression levels peak during 11 dpc: also detected at slightly lower levels during 7 dpc, 15 dpc and 17 dpc (PubMed:16990280).|||Expressed at highest levels in the kidney, where it is primarily detected in the epithelial cells of distal tubules and collecting ducts, and more weakly in proximal epithelial cells. Expressed at lower levels in heart and lung (at protein level). Detected in skeletal muscle.|||May inhibit TGF-beta signaling.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Bsg ^@ http://purl.uniprot.org/uniprot/P18572 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||By estrogen in the uterine epithelium of ovariectomized animals. By eCG in ovary.|||Cell membrane|||Endoplasmic reticulum membrane|||Essential for normal retinal maturation and development (PubMed:10967074, PubMed:11273674, PubMed:11853760). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687).|||In developing eye expressed at embryonic days 12 dpc, 15 dpc and 18 dpc, and at postnatal days P1, P7, P14, and P21. Expression progressed from a more generalized distribution throughout the undifferentiated neural retina to specific staining of retina-pigmented epithilia, the MCs, photoreceptor cells and the ciliary apparatus. Expression is highest at P21. Isoform 1 and isoform 2 are expressed at equivalent levels at P7, isoform 1 is more abundant at P14, P21 and P28. In uterus during the peri-implantation period strongly expressed in luminal and glandular epithelium on day 1 of pregnancy and gradually decreased to a basal level from day 2-4 of pregnancy. Expression in the sub-luminal stroma was first detected on day 3 of pregnancy and increased on day 4 of pregnancy. On day 5 of pregnancy, the expression of basigin protein and mRNA was only detected in the implanting embryos, and the luminal epithelium and sub-luminal stroma surrounding the embryos. In ovary during sexual maturation expressed in the granulosa cells of preantral follicles at days 20 and 25 after birth. Expressed during corpus luteum formation.|||Interacts with ATP1B2, MAG and L1CAM (PubMed:12558975). Interacts with SLC16A7 (PubMed:21792931). Interacts with VEGFA, KDR/VEGFR2, PPIA/CYPA, SLC1A3, SLC16A11 and SLC16A12 (By similarity). Interacts with PPIL2; regulates BSG transport to the cell membrane (By similarity). Interacts with SLC16A1; interaction mediates SLC16A1 targeting to the plasma membrane (By similarity). Interacts with SLC16A3; interaction mediates SLC16A3 targeting to the plasma membrane (By similarity).|||Interacts with NXNL1 (PubMed:25957687). Interacts with SLC2A1 and SLC16A1/GLUT1 (By similarity). Interacts with XKR8; promoting its localization at the cell membrane (PubMed:27503893).|||Interacts with SLC16A6; this interaction mediates targeting to the plasma membrane.|||Male mice are sterile, testis lack elongated spermatids and mature spermatozoa, spermatogenesis is arrested at the early round spermatid stages before any spermatid differentiation occurrs and a large increase in the number of germ cells undergoing apoptosis is seen in the testis (PubMed:23727514). Mice are visually impaired at the time of eye opening (2 weeks of age), despite normal retina architecture at that age (PubMed:10967074, PubMed:11273674, PubMed:11853760). At visual maturity (3 weeks of age), the photoreceptor outer segments appear less dense and shorter than those of control animals, and at 8 weeks, retinal degeneration is observed (PubMed:10967074, PubMed:11273674, PubMed:11853760).|||N-glycosylated (PubMed:12558975, PubMed:23727514). During spermatogenesis, probably deglycosylated during epididymal transit (PubMed:11882021).|||N-glycosylated.|||Photoreceptor inner segment|||Retina-specific (PubMed:12939332, PubMed:11273674, PubMed:11853760, PubMed:25957687). Expressed in both rods and cones (at protein level) (PubMed:25957687).|||Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (By similarity). Plays an important role in targeting the monocarboxylate transporters SLC16A1, SLC16A3 and SLC16A8 to the plasma membrane (PubMed:12601063). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (By similarity). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA and KDR/VEGFR2 in endothelial cells (By similarity). Plays an important role in spermatogenesis; mediates interactions between germ cells and Sertoli cell and is essential for the development/differentiation of germ cells to round spermatids (PubMed:23727514, PubMed:11882021).|||Testis and caput, corpus and cauda epididymides (at protein level) (PubMed:11882021, PubMed:23727514, PubMed:21792931). Expressed in the brain, lung, liver, kidney, heart, spleen, uterus, retina and skeletal muscle (PubMed:2361961, PubMed:12939332, PubMed:12601063).|||photoreceptor outer segment http://togogenome.org/gene/10090:Spr ^@ http://purl.uniprot.org/uniprot/Q91XH5 ^@ Similarity ^@ Belongs to the sepiapterin reductase family. http://togogenome.org/gene/10090:Hsf4 ^@ http://purl.uniprot.org/uniprot/B2RQY2|||http://purl.uniprot.org/uniprot/Q9R0L1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HSF family.|||Heat-shock transcription factor that specifically binds heat shock promoter elements (HSE) (By similarity). Required for denucleation and organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (By similarity). In this process, may regulate denucleation of lens fiber cells in part by activating DNASE2B transcription (By similarity). May be involved in DNA repair through the transcriptional regulation of RAD51 (By similarity). May up-regulate p53/TP53 protein in eye lens fiber cells, possibly through protein stabilization (By similarity). In the eye lens, controls the expression of alpha-crystallin B chain/CRYAB and consequently may be involved in the regulation of lysosomal acidification (PubMed:31786107).|||Homotrimer (PubMed:10488131). Exhibits constitutive DNA binding and forms trimers even in the absence of stress (PubMed:10488131). Interacts with ALKBH4, DUSP26, MAPK1, MAPK2, MAPK8 and MAP kinase p38 (By similarity).|||Isoform HSF4B is constitutively sumoylated. Sumoylation represses the transcriptional activity and is promoted by phosphorylation on Ser-298. HSFA is not sumoylated (By similarity).|||Nucleus|||Phosphorylated mainly on serine residues. Phosphorylation on Ser-298 promotes sumoylation on Lys-293 (By similarity).|||Preferentially expressed in brain and lung. Also found in the eye. Slightly detected in liver and skeletal muscle. Isoform B is the major species in various tissues.|||Transcriptional activator.|||Transcriptional repressor. http://togogenome.org/gene/10090:Gpr6 ^@ http://purl.uniprot.org/uniprot/Q6YNI2 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice show reduced striatal cyclic AMP production and selective alterations in instrumental conditioning.|||Mainly expressed in the brain. Selectively expressed in striatopallidal neurons in the striatum.|||Orphan receptor with constitutive G(s) signaling activity that activate cyclic AMP. Promotes neurite outgrowth and blocks myelin inhibition in neurons (By similarity).|||Was originally (PubMed:14592418) thought to be a receptor for sphingosine 1-phosphate. It has been demonstrated that it is not the case in human. http://togogenome.org/gene/10090:Coprs ^@ http://purl.uniprot.org/uniprot/Q9CQ13 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Histone-binding protein required for histone H4 methyltransferase activity of PRMT5. Specifically required for histone H4 'Arg-3' methylation mediated by PRMT5, but not histone H3 'Arg-8' methylation, suggesting that it modulates the substrate specificity of PRMT5. Specifically interacts with the N-terminus of histone H4 but not with histone H3, suggesting that it acts by promoting the association between histone H4 and PRMT5. Involved in CCNE1 promoter repression (By similarity). Plays a role in muscle cell differentiation by modulating the recruitment of PRMT5 to the promoter of genes involved in the coordination between cell cycle exit and muscle differentiation.|||Interacts with PRMT5. Interacts with histone H4; specifically interacts with the N-terminus of histone H4 but not with histone H3 (By similarity). Interacts with CBFB. Found in a complex with PRMT5, RUNX1 and CBFB.|||Nucleus http://togogenome.org/gene/10090:Gid4 ^@ http://purl.uniprot.org/uniprot/Q9CPY6 ^@ Caution|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the GID4/VID24 family.|||Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles.|||Substrate-recognition subunit of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. Binds proteins and peptides with a Pro/N-degron consisting of an unmodified N-terminal Pro followed by a small residue, and has the highest affinity for the peptide Pro-Gly-Leu-Trp. Binds peptides with an N-terminal sequence of the type Pro-[Ala,Gly]-[Leu,Met,Gln,Ser,Tyr]-[Glu,Gly,His,Ser,Val,Trp,Tyr]. Does not bind peptides with an acetylated N-terminal Pro residue.|||The first four residues of target peptides with a free N-terminal Pro (a Pro/N-degron) are bound inside a deep and narrow beta-barrel structure.|||The human orthologous sequence is longer in the N-terminus. http://togogenome.org/gene/10090:Itln1 ^@ http://purl.uniprot.org/uniprot/O88310 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By infection with the helminth parasite N.brasiliensis.|||Cell membrane|||Constitutive expression does not lead to enhanced immunity to N.brasiliensis or M.tuberculosis.|||Expressed in small intestinal Paneth cells in uninfected mice. Expression also detected in various other tissues including stomach, kidney, ovary and brain.|||In the embryo, levels are highest at day 7, decrease by mid-embryogenesis at day 11 and increase again in late embryogenesis at day 17.|||Lectin that specifically recognizes microbial carbohydrate chains in a calcium-dependent manner (PubMed:26148048). Binds to microbial glycans that contain a terminal acyclic 1,2-diol moiety, including beta-linked D-galactofuranose (beta-Galf), D-phosphoglycerol-modified glycans, D-glycero-D-talo-oct-2-ulosonic acid (KO) and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO). Binds to glycans from Gram-positive and Gram-negative bacteria, including K.pneumoniae, S.pneumoniae, Y.pestis, P.mirabilis and P.vulgaris. Does not bind mammalian glycans. Probably plays a role in the defense system against microorganisms. May function as adipokine that has no effect on basal glucose uptake but enhances insulin-stimulated glucose uptake in adipocytes. Increases AKT phosphorylation in the absence and presence of insulin. May interact with lactoferrin/LTF and increase its uptake, and may thereby play a role in iron absorption (By similarity).|||Monomer (PubMed:17621593). May interact with LTF (By similarity).|||Secreted http://togogenome.org/gene/10090:Aifm2 ^@ http://purl.uniprot.org/uniprot/Q8BUE4 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A NAD(P)H-dependent oxidoreductase that acts as a key inhibitor of ferroptosis (By similarity). At the plasma membrane, catalyzes reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and consequently ferroptosis (By similarity). Acts in parallel to GPX4 to suppress phospholipid peroxidation and ferroptosis (By similarity). This anti-ferroptotic function is independent of cellular glutathione levels (By similarity). Also acts as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4 and menadione) to hydroquinone forms (PubMed:35922516). Hydroquinones act as potent radical-trapping antioxidants inhibitor of phospholipid peroxidation and ferroptosis (PubMed:26689472). May play a role in mitochondrial stress signaling (PubMed:26689472). Upon oxidative stress, associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct devoid of oxidoreductase activity, which then translocates from mitochondria into the nucleus triggering DNA damage and cell death (PubMed:26689472).|||Belongs to the FAD-dependent oxidoreductase family.|||Binds 6-hydroxy-FAD non-covalently.|||Cell membrane|||Cytoplasm|||Detected in most normal tissues as two transcripts of 1.8 and 4.0 kb in length, respectively. Highly expressed in liver, testis, and kidney, and expressed at lower levels in pancreas, spleen, brain and lung (PubMed:16186796). Expressed in heart (at protein level) (PubMed:26689472).|||Expression is up-regulated in mouse embryonic fibroblasts by genotoxic reagents 5-fluorouracil and etoposide (PubMed:16186796). Up-regulated in cardiac cells by anticancer drug doxorubicin (PubMed:26689472).|||Interacts with importin subunits KPNA2 and IPO5; this interaction likely mediates the translocation into the nucleus upon oxidative stress.|||Lipid droplet|||Mitochondrion membrane|||N-myristoylation at Gly-2 mediates the recruitment to lipid droplets and plasma membrane.|||Nucleus|||The modification by 4-hydroxy-2-nonenal (HNE) adduction in mitochondria results in loss of the oxidoreductase activity and activation of a novel function in mitochondrial oxidative stress signaling. http://togogenome.org/gene/10090:Rftn1 ^@ http://purl.uniprot.org/uniprot/Q6A0D4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the raftlin family.|||Cell membrane|||Cytoplasm|||Early endosome|||Endosome|||Expressed in T-cells, B-cells, thymus and spleen (at protein level) (PubMed:19414744, PubMed:12805216). Expressed in dendritic cells, macrophages, heart, lung and small intestine (PubMed:19414744).|||Interacts with TLR4; the interaction occurs in response to lipopolysaccharide stimulation. Interacts with CLTC; the interaction occurs in response to pathogens. Interacts with AP2A1 and AP2B1.|||Involved in protein trafficking via association with clathrin and AP2 complex (By similarity). Upon bacterial lipopolysaccharide stimulation, mediates internalization of TLR4 to endosomes in dendritic cells and macrophages, and internalization of poly(I:C) to TLR3-positive endosomes in myeloid dendritic cells and epithelial cells; resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production (PubMed:27022195). Involved in T-cell antigen receptor-mediated signaling by regulating tyrosine kinase LCK localization, T-cell dependent antibody production and cytokine secretion (PubMed:19414744). May regulate B-cell antigen receptor-mediated signaling (By similarity). May play a pivotal role in the formation and/or maintenance of lipid rafts (By similarity).|||Membrane raft|||Mutant mice have smaller spleen, fewer splenocytes, reduced IgM production and secrete less IFNG, during antigen re-stimulation (PubMed:19414744). Double RFTN1 and RFTN2 mutant mice show no visible phenotype under pathogen-free conditions but show greatly reduced IFNB1 production in splenic dendritic cells following poly(I:C) or LPS stimulation (PubMed:27022195). http://togogenome.org/gene/10090:Nrsn1 ^@ http://purl.uniprot.org/uniprot/P97799 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the VMP family.|||By retinoic acid in neuroblastoma Neuro2a cells. Down-regulated following fear conditioning (at protein level) (PubMed:26430118).|||Expressed predominantly in brain. Also weakly expressed in lung and spleen. In brain, expressed strongly in nerve fibers of the cerebral cortex, anterior cerebral nuclei, hypothalamus, amygdaloid complex, brain stem of the metaencephalon and medulla oblongata, and moderately expressed in soma of neurons of the dentate gyrus of the hippocampus and Purkinje cells of the cerebellum.|||Expression is developmentally regulated as axonal fibers innervate, extend collateral fibers and finally attain a stable state. First detected at postnatal day 6 in cell bodies and apical dendrites of pyramidal neurons in the developing cerebral cortex, with expression gradually increasing during postnatal development. In P1 retina, strongly expressed in the optic nerve fiber layer, and weakly expressed in ganglion cells, presumptive amacrine and horizontal cells. At P10, also strongly expressed in other parts of the retina such as the ganglion cells, inner plexiform layer and horizontal cells. Expression decreases as the retina develops further to maturity.|||May play an important role in neural organelle transport, and in transduction of nerve signals or in nerve growth (PubMed:12445626, PubMed:16527258, PubMed:16696124, PubMed:9191101). May play a role in neurite extension (PubMed:26430118).|||Membrane|||neuron projection http://togogenome.org/gene/10090:Esco2 ^@ http://purl.uniprot.org/uniprot/Q8CIB9 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Acetyltransferase required for the establishment of sister chromatid cohesion. Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during the S phase. Acetylates the cohesin component SMC3.|||At 14.5 dpc the expression is detected in developing murine lip, eyelid, palate, digit, tongue and hair follicles. Its expression is also observed in the long bones of the developing forelimb but not the hindlimb.|||Belongs to the acetyltransferase family. ECO subfamily.|||Chromosome|||Nucleus|||The N-terminal region seems to be responsible for association with chromosomes, thus excluding any involvement of the Zn finger in this process. http://togogenome.org/gene/10090:Pgls ^@ http://purl.uniprot.org/uniprot/D3Z4X1|||http://purl.uniprot.org/uniprot/Q9CQ60 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.|||Cytoplasm|||Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate. http://togogenome.org/gene/10090:Cxxc4 ^@ http://purl.uniprot.org/uniprot/M0QWU0 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Cyp8b1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0N7|||http://purl.uniprot.org/uniprot/O88962 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis (By similarity). Controls biliary balance of cholic acid and chenodeoxycholic acid, ultimately regulating the intestinal absorption of dietary lipids (PubMed:12393855, PubMed:28377401). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase) (By similarity).|||Belongs to the cytochrome P450 family.|||By cholestyramine treatment (PubMed:10051404). Induced upon starvation (PubMed:10051404).|||Endoplasmic reticulum membrane|||Expressed in liver.|||Knockout mice are resistant to Western diet-induced hepatic steatosis due to impaired cholic acid synthesis and deficient fat absorption.|||Microsome membrane http://togogenome.org/gene/10090:Ston1 ^@ http://purl.uniprot.org/uniprot/Q8CDJ8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Stoned B family.|||Cytoplasm|||In contrast to other members of the family, it does not contain NPF (Asn-Pro-Phe) sites and thereby does not interact with EPS15, EPS15R and ITSN1.|||May be involved in the endocytic machinery.|||Membrane http://togogenome.org/gene/10090:Dars2 ^@ http://purl.uniprot.org/uniprot/Q8BIP0 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family. Type 1 subfamily.|||Homodimer.|||Mitochondrion matrix http://togogenome.org/gene/10090:Gsdmc ^@ http://purl.uniprot.org/uniprot/Q99NB5 ^@ Activity Regulation|||Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage by CASP8 relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-C, N-terminal) that initiates pyroptosis.|||Despite its name, does not contain a functional leucine zipper.|||Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.|||Pore-forming protein that causes membrane permeabilization and pyroptosis. Produced by the cleavage of gasdermin-D by caspase CASP8 in response to death signals. After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids. Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis.|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-C, N-terminal) following cleavage by caspase CASP8.|||This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-C, N-terminal) binds to membranes and forms pores, triggering pyroptosis.|||cytosol http://togogenome.org/gene/10090:Lmx1a ^@ http://purl.uniprot.org/uniprot/Q543W2|||http://purl.uniprot.org/uniprot/Q9JKU8 ^@ Disease Annotation|||Function|||Subcellular Location Annotation ^@ Acts as a transcriptional activator by binding to an A/T-rich sequence, the FLAT element, in the insulin gene promoter. Required for development of the roof plate and, in turn, for specification of dorsal cell fates in the CNS and developing vertebrae.|||Defects in Lmx1a are the cause of the spontaneous neurologic mutant mouse, called 'dreher' (dr) and results from a failure of the roof plate to develop.|||Nucleus http://togogenome.org/gene/10090:Dnajc27 ^@ http://purl.uniprot.org/uniprot/Q8CFP6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed. May act as a nuclear scaffold for MAPK1, probably by association with MAPK1 nuclear export signal leading to enhanced ERK1/ERK2 signaling.|||Interacts directly with MAPK1 (wild-type and kinase-deficient forms). Interacts directly (in GTP-bound form) with MAP2K1 (wild-type and kinase-deficient forms).|||Nucleus http://togogenome.org/gene/10090:Ppp1r3b ^@ http://purl.uniprot.org/uniprot/Q8C767 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subunit|||Tissue Specificity ^@ Acts as a glycogen-targeting subunit for phosphatase PP1. Facilitates interaction of the PP1 with enzymes of the glycogen metabolism and regulates its activity. Suppresses the rate at which PP1 dephosphorylates (inactivates) glycogen phosphorylase and enhances the rate at which it activates glycogen synthase and therefore limits glycogen breakdown. Its activity is inhibited by PYGL, resulting in inhibition of the glycogen synthase and glycogen phosphorylase phosphatase activities of PP1. Dramatically increases basal and insulin-stimulated glycogen synthesis upon overexpression in hepatocytes (By similarity).|||Expressed in lung at 12.5 and 16.5 dpc and declines thereafter. Expressed in epithelial cells of the bronchus and smooth muscle of the pulmonary artery at 13.5 and 16.5 dpc.|||Highly expressed in liver (at protein level). Expressed predominantly in liver. Expressed moderately in heart. Expressed weakly in prostate, stomach, thyroid, lung, kidney, spleen and skeletal muscle.|||Interacts with glycogen, PPP1CC catalytic subunit of PP1 and PYGL. Associates with glycogen particles. Forms complexes with debranching enzyme, glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity (By similarity).|||The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to PYGL.|||Up-regulated by TITF1. http://togogenome.org/gene/10090:Slc37a4 ^@ http://purl.uniprot.org/uniprot/Q9D1F9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.|||Membrane http://togogenome.org/gene/10090:Prim2 ^@ http://purl.uniprot.org/uniprot/P33610 ^@ Cofactor|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the eukaryotic-type primase large subunit family.|||Binds 1 [4Fe-4S] cluster.|||Heterodimer of a catalytic subunit PRIM1 and a regulatory subunit PRIM2, also known as the DNA primase complex (PubMed:8026492, PubMed:8253737). Interacts via (C-terminus) with PRIM1 (By similarity). Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:8253737). Within the complex, POLA1 directly interacts with PRIM2 (PubMed:8026492).|||Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:8026492, PubMed:8253737). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:8253737). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:8253737). Binds RNA:DNA duplex and coordinates the catalytic activities of PRIM1 and POLA2 during primase-to-polymerase switch.|||The RNA:DNA duplex-binding domain interacts with the template phosphates at positions -2, -1, 1, and 2 positioning its bases -1, 1, and 2 for duplex formation. Interacts only with the beta- and gamma-phosphates of triphosphate moiety of initiating NTP of the primer. The side chain of His-303 mimics a RNA base that would be paired with the template nucleotide at position -1 via a hydrogen bond, thereby facilitating the stacking of the initiating NTP. In the initiating primosome a 'mini RNA:DNA' duplex is formed comprising three template nucleotides at positions -1, 1, and 2 on one strand and His-303, initiating NTP, and incoming NTP on the other strand.|||The interdomain linker provides flexibility in movement relative to primosome platform composed of PRIM1, the N-terminus of PRIM2, the C-terminus of POLA1 and POLA2. Together with POLA1 interdomain linker, allows for large-scale conformational changes of primosome and coordinated autoregulation of catalytic centers of PRIM1 and POLA1. It is proposed to move the C-terminus of PRIM2 close to PRIM1 during initiation, then move it away with the 5'-end of the nascent primer during elongation. The steric hindrance between the N- and C-terminus of PRIM2 as the RNA primer is elongated limits its length to 9 nucleotides. Ultimately a large rotation of the C-terminus of PRIM2 transfers the primer to POLA1 active site for DNA synthesis. http://togogenome.org/gene/10090:Fam187a ^@ http://purl.uniprot.org/uniprot/Q9D3R5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM187 family.|||Membrane http://togogenome.org/gene/10090:Ano8 ^@ http://purl.uniprot.org/uniprot/Q6PB70 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anoctamin family.|||Cell membrane|||Detected in the mantle layer of the neural tube and in the dorsal root ganglia at 14.5 dpc.|||Does not exhibit calcium-activated chloride channel (CaCC) activity.|||Predominant expression seen in epithelial tissues.|||The term 'anoctamin' was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology. http://togogenome.org/gene/10090:Pik3cg ^@ http://purl.uniprot.org/uniprot/Q3UVA4|||http://purl.uniprot.org/uniprot/Q8C5Q7|||http://purl.uniprot.org/uniprot/Q9JHG7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunit PIK3R5 leading to the translocation from the cytosol to the plasma membrane and to kinase activation; the respective activation involving PIK3R6 requires HRAS for membrane recruitment. Wortmannin sensitive in nM range. Inhibited by AS252424.|||Autophosphorylation at Ser-1101 has no effect on the phosphatidylinositol-4,5-bisphosphate 3-kinase activity.|||Belongs to the PI3/PI4-kinase family.|||Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.|||Cell membrane|||Cytoplasm|||Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with GRK2 through the PIK helical domain (By similarity). Interaction with GRK2 is required for targeting to agonist-occupied receptor. Interacts with PDE3B; regulates PDE3B activity and thereby cAMP levels in cells (PubMed:15294162). Interacts with TPM2 (By similarity). Interacts with EPHA8; regulates integrin-mediated cell adhesion to substrate. Interacts with HRAS; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6.|||PIK3CG-null mice are viable and fertile, and display immunological abnormalities when the immune system is stressed. There is reduced T(reg) cells amount, reduced levels of IgG, enhanced IL12 production in macrophages, and increased T-cell infiltration in the gut (PubMed:31554793). Leukocyte migration in response to chemotactic agents and towards the site of inflammation, as well as neutrophil oxidative burst in response to chemotactic agents are decreased. Mutant mice show reduced thymocyte survival, defective T lymphocyte activation, and are protected from leukocyte infiltration of synovia in a model of rheumatoid arthritis. Dendritic cell showed reduced response to chemokines and migration to draining lymph nodes under inflammatory conditions. Platelets have defects in thrombus formation. PIK3CG-null mice show increased cardiac contractility, and display myocardial damage after transverse aortic constriction.|||Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contribute to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis (By similarity).|||Phosphorylated at Thr-1024 by PKA. Phosphorylation inhibits lipid kinase activity. http://togogenome.org/gene/10090:Ncoa7 ^@ http://purl.uniprot.org/uniprot/Q6DFV7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OXR1 family.|||Enhances the transcriptional activities of several nuclear receptors. Involved in the coactivation of different nuclear receptors, such as ESR1, THRB, PPARG and RARA (By similarity).|||Highly expressed in brain and kidney. Weakly expressed in mammary gland, lung and testis. In brain, expression is found in neurons of cerebral cortex, thalamus, hypothalamus, hippocampus, cerebellum, striatum and choroid plexus.|||Interacts with ESR1, ESR2A, ESR2B, THRB, PPARG and RARA in a ligand-inducible manner. Interacts with the heterodimer AHR-ARNT (By similarity).|||Nucleus http://togogenome.org/gene/10090:Usp9y ^@ http://purl.uniprot.org/uniprot/F8VPU6 ^@ Similarity ^@ Belongs to the peptidase C19 family. http://togogenome.org/gene/10090:Ifnb1 ^@ http://purl.uniprot.org/uniprot/P01575|||http://purl.uniprot.org/uniprot/Q0VE17 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alpha/beta interferon family.|||Mice show impaired antiviral activity and are highly susceptible to vaccinia virus infection (PubMed:10708458). Mice show spontaneous neurodegeneration: mice display motor and cognitive learning impairments associated with alpha-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region (PubMed:26451483). Mice also show defects in adaptive immunity: bone marrow cells display B-cells maturation defects, and bone marrow macrophages show impaired myelopoiesis and lipopolysaccharide (LPS)-inducible production of tumor necrosis factor (PubMed:14597717). Deletion leads to increased and chronic demyelination in mouse models of experimental autoimmune encephalitis (EAE) (PubMed:12707359).|||Monomer.|||Secreted|||This beta interferon does not have a disulfide bond.|||Type I interferon cytokine that plays a key role in the innate immune response to infection, developing tumors and other inflammatory stimuli (PubMed:10708458, PubMed:23872679). Signals via binding to high-affinity (IFNAR2) and low-affinity (IFNAR1) heterodimeric receptor, activating the canonical Jak-STAT signaling pathway resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response, such as antiviral proteins, regulators of cell proliferation and differentiation, and immunoregulatory proteins (By similarity). Signals mostly via binding to a IFNAR1-IFNAR2 heterodimeric receptor, but can also function with IFNAR1 alone and independently of Jak-STAT pathways (PubMed:23872679). Elicits a wide variety of responses, including antiviral and antibacterial activities, and can regulate the development of B-cells, myelopoiesis and lipopolysaccharide (LPS)-inducible production of tumor necrosis factor (PubMed:10708458, PubMed:14597717). Plays a role in neuronal homeostasis by regulating dopamine turnover and protecting dopaminergic neurons: acts by promoting neuronal autophagy and alpha-synuclein clearance, thereby preventing dopaminergic neuron loss (PubMed:26451483). IFNB1 is more potent than interferon-alpha (IFN-alpha) in inducing the apoptotic and antiproliferative pathways required for control of tumor cell growth (PubMed:14597717). http://togogenome.org/gene/10090:Son ^@ http://purl.uniprot.org/uniprot/Q9QX47 ^@ Domain|||Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By leptin. Highly expressed in hypothalamus following leptin injection.|||Contains 8 types of repeats which are distributed in 3 regions.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with SRSF2. Associates with the spliceosome. Interacts with USH1G.|||Nucleus speckle|||RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3' (By similarity). Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (By similarity). May also regulate the ghrelin signaling in hypothalamic neuron by acting as a negative regulator of GHSR expression (PubMed:20876580).|||Widely expressed. Highly expressed in brain, heart, spleen, liver, skeletal muscle, kidney and testis. http://togogenome.org/gene/10090:Azin2 ^@ http://purl.uniprot.org/uniprot/A8Y5E7|||http://purl.uniprot.org/uniprot/B2RSR5|||http://purl.uniprot.org/uniprot/Q6P078|||http://purl.uniprot.org/uniprot/Q8BVM4 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme-binding (PubMed:18062773, PubMed:18508777, PubMed:18973822). Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production (PubMed:16916800, PubMed:24967154). Participates in the morphological integrity of the trans-Golgi network (TGN) and functions as a regulator of intracellular secretory vesicle trafficking (By similarity).|||Belongs to the Orn/Lys/Arg decarboxylase class-II family.|||Belongs to the Orn/Lys/Arg decarboxylase class-II family. ODC antizyme inhibitor subfamily.|||Cytoplasm|||Cytoplasmic granule|||Cytoplasmic vesicle|||Endoplasmic reticulum-Golgi intermediate compartment|||Expressed in the medulla and chromaffin cells of the adrenal gland. Expressed in the Langerhans islets of the pancreas. Expressed in the inner part of the seminiferous tubules and in spermatozoa located in the lumen of the epididymis of the testis. Expressed in the cortex, hippocampus and cerebellum of the brain. Expressed in normal and neoplastic mast cells (MC) (at protein level). Expressed in testis, pancreas and brain. Expressed throughout the differentiation process from spermatids to spermatozoa in the inner part of the seminiferous tubules. Expressed in the kidney: expressed in the superficial (Cs) and the deep layer (Cd) of the cortex region and in the outer stripe (OS), inner stripe (IS) and the inner medulla papilla (IM) of the medulla region.|||Gly-70 is present instead of the conserved Lys which would otherwise be the covalent pyridoxal phosphate binding site.|||Membrane|||Monomer. Interacts with OAZ1, OAZ2 and OAZ3; this interaction disrupts the interaction between the antizyme and ODC1. Does not form a heterodimer with ODC1.|||Nucleus|||Perikaryon|||Previously reported to be localized in the mitochondrion (PubMed:16916800). However, it was not confirmed by later reports (PubMed:18062773).|||The N-terminus domain is necessary for its localization to the ER-Golgi intermediate compartment (ERGIC).|||The human ortholog was initially reported to have ornithine or arginine decarboxylase activities, but it was later found to possess neither of them.|||Ubiquitinated, leading to its proteasomal degradation; a process that is reduced in presence of antizymes. May also be degraded through the lysosomal degradative pathway in a proteasomal-independent manner.|||axon|||cis-Golgi network|||dendrite|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Pnrc2 ^@ http://purl.uniprot.org/uniprot/Q9CR73 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PNRC family. PNRC2 subfamily.|||Interacts with UPF1/RENT1; preferentially interacts with hyperphosphorylated form. Interacts with DCP1A. Interacts with many nuclear receptors including ESR1, ESRRA, ESRRG, NR3C1/GR, NR5A1, PGR, TR, RAR and RXR.|||Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery (By similarity). May act by targeting the NMD machinery to the P-body and recruiting the decapping machinery to aberrant mRNAs (By similarity). Required for UPF1/RENT1 localization to the P-body (By similarity). Plays a role in glucocorticoid receptor-mediated mRNA degradation by interacting with the glucocorticoid receptor NR3C1 in a ligand-dependent manner when it is bound to the 5' UTR of target mRNAs and recruiting the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (By similarity). Also acts as a nuclear receptor coactivator. May play a role in controlling the energy balance between energy storage and energy expenditure (PubMed:17971453).|||Mice are lean, resistant to high fat diet-induced obesity but without the induction of insulin resistance and have a higher metabolic rate than wild-type mice.|||Nucleus|||P-body|||Strong expression is detected in lung, spleen, ovary, thymus, and colon.|||The interaction between PNRC2 and nuclear receptors is dependent on the SH3 binding motif. http://togogenome.org/gene/10090:Or6b6 ^@ http://purl.uniprot.org/uniprot/Q9EPG2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:H3c11 ^@ http://purl.uniprot.org/uniprot/P68433 ^@ Developmental Stage|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.|||Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).|||Belongs to the histone H3 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).|||Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.|||Hydroxybutyrylation of histones is induced by starvation. It is linked to gene activation and may replace histone acetylation on the promoter of specific genes in response to fasting.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression (By similarity).|||Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.|||Nucleus|||Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.|||Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).|||Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).|||Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (By similarity).|||This histone is only present in mammals.|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins (By similarity). Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination. http://togogenome.org/gene/10090:Rars ^@ http://purl.uniprot.org/uniprot/Q9D0I9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Cytoplasm|||Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis (PubMed:12060739). Modulates the secretion of AIMP1 and may be involved in generation of the inflammatory cytokine EMAP2 from AIMP1.|||Interacts (via N-terminus) with AIMP1 (via N-terminus); this stimulates its catalytic activity. Interacts (via N-terminus) with LARS2 (via C-terminus). Monomer (By similarity). Part of a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:12060739). Interacts with QARS1. Part of a complex composed of RARS1, QARS1 and AIMP1 (By similarity).|||The alpha-helical N-terminus (residues 1-72) mediates interaction with AIMP1 and thereby contributes to the assembly of the multisynthetase complex.|||cytosol http://togogenome.org/gene/10090:Upp1 ^@ http://purl.uniprot.org/uniprot/P52624|||http://purl.uniprot.org/uniprot/Q5SUC8 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subunit ^@ Belongs to the PNP/UDP phosphorylase family.|||By a mixture of inflammatory cytokines: TNF-alpha, IL-1 and interferon gamma.|||Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate (PubMed:7744869). The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.|||Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.|||Homodimer.|||Strongly inhibited by 2,2'-anhydro-5-ethyluridine, a competitive inhibitor.|||The N-terminus is blocked. http://togogenome.org/gene/10090:Pacrg ^@ http://purl.uniprot.org/uniprot/Q9DAK2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Forms a large molecular chaperone complex containing heat shock proteins 70 and 90 and chaperonin components. Interacts with STIP1, PRKN, GPR37, HSPA8, TCP1/CCT1, CCT2, CCT3, CCT4, CCT5, CCT6A, CCT7 and CCT8 (By similarity). Interacts with MEIG1.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). Suppresses cell death induced by accumulation of unfolded Pael receptor (Pael-R, a substrate of Parkin). Facilitates the formation of inclusions consisting of Pael-R, molecular chaperones, protein degradation molecules and itself when proteasome is inhibited. May play an important role in the formation of Lewy bodies and protection of dopaminergic neurons against Parkinson disease (By similarity).|||cilium axoneme http://togogenome.org/gene/10090:Kdr ^@ http://purl.uniprot.org/uniprot/P35918 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-949 is important for interaction with SH2D2A/TSAD and VEGFA-mediated reorganization of the actin cytoskeleton. Phosphorylation at Tyr-1173 is important for interaction with PLCG1 and SHB. Phosphorylation at Tyr-1212 is important for interaction with NCK1 and FYN. Dephosphorylated by PTPRJ at Tyr-799, Tyr-949, Tyr-994, Tyr-1052, Tyr-1057, Tyr-1173 and Tyr-1212 (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell junction|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle|||Early endosome|||Embryonic lethality at 8.5 to 9.5 dpc, due to early defects in the development of hematopoietic and endothelial cells, leading to defects in vasculogenesis and endocardium development. At 7.5 dpc, there are no blood islands in the yolk sac. Organized blood vessels are absent in the yolk sac and in the embryo.|||Endoplasmic reticulum|||Expressed in endothelial cells (at protein level). Detected in embryonic endothelial cells, as well as hematopoietic stem and progenitor cells. Detected in vascular endothelium. Expressed at high levels in adult heart, lung, kidney, brain and skeletal muscle, but is also expressed at lower levels in most other adult tissues.|||Expressed in endothelial cells of allantois/umbilical vessels at 8.5 dpc (at protein level). Increases moderately during pregnancy (maximum 2.7-fold at 19 days), and increases further during lactation (maximum 3.7-fold increase on day 7).|||Homodimer in the presence of bound dimeric VEGFA, VEGFC or VEGFD ligands; monomeric in the absence of bound ligands. Can also form heterodimers with FLT1/VEGFR1 and KDR/VEGFR2. Interacts (tyrosine phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine-phosphorylated active form preferentially) with DAB2IP (via C2 domain and active form preferentially); the interaction occurs at the late phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6 (PubMed:12796773, PubMed:12881528, PubMed:15026417, PubMed:15673613, PubMed:17702744, PubMed:19668192, PubMed:7681362, PubMed:8356051). Interacts (via C-terminus domain) with ERN1 (via kinase domain); the interaction is facilitated in a XBP1 isoform 1- and vascular endothelial growth factor (VEGF)-dependent manner in endothelial cells (By similarity). Interacts (via juxtamembrane region) with chaperone PDCL3 (via thioredoxin fold region); the interaction leads to increased KDR/VEGFR2 abundance through inhibition of its ubiquitination and degradation (By similarity). Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via SH2-like region); binding requires autophosphorylation of the KDR/VEGFR2 C-terminal region (By similarity). Interacts with isoform 2 of BSG (By similarity). Interacts with SLC31A1; this interaction is induced upon VEGFA stimulation leading to SLC31A1 and KDR subsequent co-internalization to early endosomes, thereby activating KDR downstream signaling in endothelial cells (By similarity).|||N-glycosylated.|||Nucleus|||Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization and activation by autophosphorylation on tyrosine residues. May be regulated by hydrogen sulfide (H(2)S) levels via a sensitive intracellular disulfide bond (By similarity).|||Secreted|||The inhibitory disulfide bond between Cys-1022 and Cys-1043 may serve as a specific molecular switch for H(2)S-induced modification that regulates KDR/VEGFR2 function.|||The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFC binding.|||Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as a negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and by preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.|||Ubiquitinated. Tyrosine phosphorylation of the receptor promotes its poly-ubiquitination, leading to its degradation via the proteasome or lysosomal proteases (By similarity). http://togogenome.org/gene/10090:Defb4 ^@ http://purl.uniprot.org/uniprot/P82019 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Exhibits antimicrobial activity against Gram-negative bacteria and Gram-positive bacteria. May act as a ligand for C-C chemokine receptor CCR6. Can bind to mouse (but not human) CCR6 and induce chemotactic activity of CCR6-expressing cells (PubMed:20068036).|||Secreted|||Tongue, esophagus and trachea. http://togogenome.org/gene/10090:Pdf ^@ http://purl.uniprot.org/uniprot/S4R2K0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the polypeptide deformylase family.|||Binds 1 Co(2+) ion.|||Homodimer.|||Mitochondrion|||Removes the formyl group from the N-terminal Met of newly synthesized proteins. http://togogenome.org/gene/10090:Sgo1 ^@ http://purl.uniprot.org/uniprot/Q9CXH7 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shugoshin family.|||Interacts with PPP2CA (or PPP2CB), PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E, SET, LRRC59, RBM10 (or RBM5), RPL10A, RPL28, RPL7, RPL7A and RPLP1. Interaction with protein phosphatase 2A occurs most probably through direct binding to the regulatory B56 subunits: PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E. Interacts with PPP2R1A and NEK2. Interacts with CDCA8 (By similarity).|||Nucleus|||Phosphorylation by NEK2 is essential for chromosome congression in mitosis and for the proper attachment of spindle microtubule to the kinetochore. Phosphorylated by PLK1 and AUKRB (By similarity).|||Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Involved in centromeric enrichment of AUKRB in prometaphase.|||Shugoshin is Japanese for guardian spirit (as it is known to be a protector of centromeric cohesin).|||Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.|||Ubiquitously expressed in proliferating cells. Moderately expressed in the oocytes.|||centromere|||centrosome|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Smyd3 ^@ http://purl.uniprot.org/uniprot/Q9CWR2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family.|||Cytoplasm|||Histone methyltransferase activity strongly stimulated by HSPCA.|||Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. Also methylates 'Lys-5' of histone H4. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences.|||Interacts with HSPCA. Interacts with HELZ. Interacts with POLR2A; the interaction may be indirect and may be mediated by HELZ. Interacts with HSP90AA1; this interaction enhances SMYD3 histone-lysine N-methyltransferase.|||Nucleus http://togogenome.org/gene/10090:Tpk1 ^@ http://purl.uniprot.org/uniprot/Q9R0M5 ^@ Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the thiamine pyrophosphokinase family.|||Catalyzes the phosphorylation of thiamine to thiamine pyrophosphate. Can also catalyze the phosphorylation of pyrithiamine to pyrithiamine pyrophosphate.|||Detected in kidney and liver, and at lower levels in heart, brain and testis.|||Homodimer.|||May be due to intron retention. http://togogenome.org/gene/10090:Slc35g2 ^@ http://purl.uniprot.org/uniprot/D3YVE8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC35G solute transporter family.|||Cell membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Drp2 ^@ http://purl.uniprot.org/uniprot/Q05AA6 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Detected in quadriceps nerve Schwann cells (PubMed:22764250). Detected in sciatic nerve (PubMed:11430802, PubMed:22764250). Detected in trigeminal nerve Schwann cells (at protein level) (PubMed:11430802). Detected in brain and spinal cord (PubMed:8640231).|||Interacts with PRX; this enhances phosphorylation (PubMed:22764250). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (PubMed:11430802).|||Mice with a Schwann cell-specific gene disruption show no obvious impairment of nerve conduction velocity and display no visible defects of their motor skills. After six months, about 6% of their nerve fibers present myelination defects, including myelin outfoldings, focal hypermyelination, and onion bulbs with thin myelin and supernumerary Schwann cells. At the molecular level, Schwann cell-specific gene disruption impairs formation of Cajal bands and location of Prx in patches that colocalize with appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane. Cytoplasm from mutant Schwann cells forms an annulus under the cell membrane, insted of being strictly compartmentalized. Besides, mutant nerves display increased numbers of Schmidt-Lanterman incisures.|||Perikaryon|||Postsynaptic density|||Required for normal myelination and for normal organization of the cytoplasm and the formation of Cajal bands in myelinating Schwann cells (PubMed:22764250). Required for normal PRX location at appositions between the abaxonal surface of the myelin sheath and the Schwann cell plasma membrane (PubMed:22764250). Possibly involved in membrane-cytoskeleton interactions of the central nervous system.|||dendrite http://togogenome.org/gene/10090:Lrit2 ^@ http://purl.uniprot.org/uniprot/Q6PFC5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tgm6 ^@ http://purl.uniprot.org/uniprot/Q8BM11 ^@ Cofactor|||Similarity ^@ Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 1 Ca(2+) ion per subunit. http://togogenome.org/gene/10090:Pacs2 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VLZ7|||http://purl.uniprot.org/uniprot/E9Q7E9|||http://purl.uniprot.org/uniprot/Q3V3Q7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PACS family.|||Endoplasmic reticulum|||Interacts with BID and PKD2. Interacts with SIRT1. Interacts with HDAC1. Interacts with TRPV1. Interacts with WDR37.|||Mitochondrion|||Multifunctional sorting protein that controls the endoplasmic reticulum (ER)-mitochondria communication, including the apposition of mitochondria with the ER and ER homeostasis. In addition, in response to apoptotic inducer, translocates BIB to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated BID, the release of cytochrome c, the activation of caspase-3 thereby causing cell death. May also involved in ion channel trafficking, directing acidic cluster-containing ion channels to distinct subcellular compartments (By similarity). http://togogenome.org/gene/10090:Tctn1 ^@ http://purl.uniprot.org/uniprot/Q8BZ64 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tectonic family.|||Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Regulator of Hedgehog (Hh), required for both activation and inhibition of the Hh pathway in the patterning of the neural tube. During neural tube development, it is required for formation of the most ventral cell types and for full Hh pathway activation. Functions in Hh signal transduction to fully activate the pathway in the presence of high Hh levels and to repress the pathway in the absence of Hh signals. Modulates Hh signal transduction downstream of SMO and RAB23.|||During embryonic development, it is expressed in regions that participate in Hedgehog signaling. First expressed during gastrulation stages in the ventral node. At 9.5 dpc, expressed in the gut endoderm, limb buds, notochord, somites, neural tube and floorplate.|||Null animals show disruption of nodal flow, laterality defects, and neural tube dorsalization. Basal bodies dock to the cellular plasma membrane, but fail to extend axonemes. However, cilia are present in the notochord, early gut epithelium, and mesenchymal cells surrounding the neural tube and in the limb bud. Null embryos develop an extra preaxial digit on 1 or both hindlimbs. Although sonic hedgehog (Shh) expression is normal, downstream signaling is disturbed, suggesting that Tctn1 is required for cilium-dependent Shh signal transduction.|||Part of the tectonic-like complex (also named B9 complex).|||Secreted|||Was named 'Tectonic' after the Greek word for builder.|||cilium basal body http://togogenome.org/gene/10090:Lypd6b ^@ http://purl.uniprot.org/uniprot/Q9D7F2 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Likely acts as a modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro acts on nAChRs in a subtype- and stoichiometry-dependent manner. Modulates specifically alpha-3(3):beta-4(2) nAChRs by enhancing the sensitivity to ACh, decreasing ACh-induced maximal current response and increasing the rate of desensitization to ACh; has no effect on alpha-7 homomeric nAChRs; modulates alpha-3(2):alpha-5:beta-4(2) nAChRs in the context of CHRNA5/alpha-5 variant Asn-398 but not its wild-type sequence. However, according to another report in vitro it can weakly inhibits alpha-7 nAChRs. http://togogenome.org/gene/10090:Or5d46 ^@ http://purl.uniprot.org/uniprot/Q8VG40 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gsn ^@ http://purl.uniprot.org/uniprot/P13020|||http://purl.uniprot.org/uniprot/Q6PAC1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the villin/gelsolin family.|||Binds to actin and to fibronectin. Identified in a complex composed of ACTA1, COBL, GSN and TMSB4X (By similarity). Interacts with the inactive form of EIF2AK2/PKR.|||Binds to actin and to fibronectin. Identified in a complex composed of ACTA1, COBL, GSN and TMSB4X. Interacts with the inactive form of EIF2AK2/PKR.|||Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed (By similarity). Plays a role in ciliogenesis (By similarity).|||Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis.|||Comprises six structurally related gelsolin-like (G1-G6) domains, that, in a calcium-free environment, are packed together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur (By similarity). Binding calcium may release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently (By similarity). G1 and G4 bind two Ca(2+) in a type I and in a type II manner (PubMed:24743229, PubMed:28695858, PubMed:31199804). G2, G3, G5 and G6 bind only one Ca(2+) in a type II manner (PubMed:12742020, PubMed:24743229, PubMed:28695858, PubMed:31199804). Type I Ca(2+) binding sites are shared between actin and gelsolin-like repeats G1 and G4 (PubMed:24743229, PubMed:31199804). Type I binding governs the strength of interactions between gelsolin and actin by direct participation at the binding interface (By similarity). Ca(2+) binding to G2 and G6 disrupts the interactions between G2 and G6, releases the C-terminal tail, and induces large interdomain rearrangements that result in the exposure of the F-actin-binding site on G2 and contributes to the activation of gelsolin (By similarity). Binding to phosphoinositides may inhibit the severing and capping properties of gelsolin (By similarity).|||Phosphorylated on tyrosine residues in vitro.|||Secreted|||cytoskeleton http://togogenome.org/gene/10090:Ate1 ^@ http://purl.uniprot.org/uniprot/J3QNU1|||http://purl.uniprot.org/uniprot/Q80YP1|||http://purl.uniprot.org/uniprot/Q9Z2A5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the R-transferase family.|||Cytoplasm|||Interacts with LIAT1; has a higher affinity than the other isoforms.|||Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein. This arginylation is required for degradation of the protein via the ubiquitin pathway.|||Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein. This arginylation is required for degradation of the protein via the ubiquitin pathway. Does not arginylate cysteine residues.|||Monomer (Probable). Interacts with LIAT1; LIAT1 is not a substrate of ATE1, the interaction takes place in the cytoplasm and seems to increase ATE1 arginyltransferase activity (PubMed:25369936, PubMed:33443146).|||Nucleus|||Shows significantly higher activity than isoform ATE1-2.|||Widely expressed. http://togogenome.org/gene/10090:Naaladl1 ^@ http://purl.uniprot.org/uniprot/Q7M758 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Aminopeptidase with broad substrate specificity. Has lower activity with substrates that have Asp or Glu in the P2' position, or Pro in the P3' position. Lacks activity with substrates that have both Pro in the P3' position and Asp or Glu in the P2' position. Lacks carboxypeptidase activity. Lacks dipeptidyl-peptidase IV type activity.|||Apical cell membrane|||Belongs to the peptidase M28 family. M28B subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Homodimer.|||N-glycosylated. http://togogenome.org/gene/10090:D16Ertd472e ^@ http://purl.uniprot.org/uniprot/Q9D7G4 ^@ Developmental Stage|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the EURL family.|||Expressed in brain (at protein level) (PubMed:27404227). Expressed in neural progenitor cells and postmitotic neurons of the embryonic cerebral cortex (PubMed:27404227).|||Expressed in the embryonic cortex and germinal ventricular zone (PubMed:27404227). Expressed in cells of the cortical plate and in retinal pigment epithelium and lens between 12 and 14 dpc (at protein level) (PubMed:27404227).|||Interacts with CCDC85B (PubMed:27404227).|||Plays a role in cortical progenitor cell proliferation and differentiation (PubMed:27404227). Promotes dendritic spine development of post-migratory cortical projection neurons by modulating the beta-catenin signaling pathway (PubMed:27404227). http://togogenome.org/gene/10090:Prpf40a ^@ http://purl.uniprot.org/uniprot/Q9R1C7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRPF40 family.|||Binds to WASL/N-WASP and suppresses its translocation from the nucleus to the cytoplasm, thereby inhibiting its cytoplasmic function. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. May play a role in cytokinesis. May be involved in pre-mRNA splicing.|||Interacts with the N-terminus of HTT and with the phosphorylated C-terminal domain of POLR2A (By similarity). Interacts with AKAP8L, SF1, SRPK1, ENAH, ATBF1 and MECP2. Interacts through the WW domains with formin proline-rich regions and with WASL/N-WASP.|||Nucleus matrix|||Nucleus speckle|||The WW domains are essential for localization to nuclear speckles. http://togogenome.org/gene/10090:Dctn1 ^@ http://purl.uniprot.org/uniprot/E9Q3M3|||http://purl.uniprot.org/uniprot/E9Q586|||http://purl.uniprot.org/uniprot/O08788|||http://purl.uniprot.org/uniprot/Q6NZM3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dynactin 150 kDa subunit family.|||Cytoplasm|||Monomer and homodimer (By similarity). Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. DCTN1/p150(glued) binds directly to microtubules and to cytoplasmic dynein. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Interacts with FBXL5. Interacts with ECPAS. Interacts with CLIP1. Interacts with CLN3 and DYNAP. Interacts with MISP; this interaction regulates its distribution at the cell cortex. Interacts with CEP131. Interacts with CEP126. Interacts with dynein intermediate chain and dynein heavy chain. Interacts with PLK1 (via POLO-box domain). Interacts with TBCB and PARD6A (By similarity). Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules (PubMed:16954346). Interacts with KIF3A (PubMed:23386061). Interacts with HPS6 (PubMed:25189619). Interacts with SNX6 (PubMed:19935774). Interacts with BICD2 (PubMed:22956769). Interacts with DST (isoform 1) (PubMed:14581450). Identified in a complex with MREG and RILP (PubMed:22275436). Interacts with BCCIP. Interacts with DCDC1 (By similarity). Interacts with AKNA (PubMed:30787442). Interacts with DYNC1I2 (PubMed:27474409).|||Nucleus envelope|||Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Essential for targeting dynein to microtubule plus ends, recruiting dynein to membranous cargos and enhancing dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Can also act as a brake to slow the dynein motor during motility along the microtubule. Can regulate microtubule stability by promoting microtubule formation, nucleation and polymerization and by inhibiting microtubule catastrophe in neurons. Inhibits microtubule catastrophe by binding both to microtubules and to tubulin, leading to enhanced microtubule stability along the axon. Plays a role in metaphase spindle orientation. Plays a role in centriole cohesion and subdistal appendage organization and function. Its recruitment to the centriole in a KIF3A-dependent manner is essential for the maintenance of centriole cohesion and the formation of subdistal appendage. Also required for microtubule anchoring at the mother centriole. Plays a role in primary cilia formation (By similarity).|||Phosphorylation by SLK at Thr-145, Thr-146 and Thr-147 targets DCTN1 to the centrosome. It is uncertain if SLK phosphorylates all three threonines or one or two of them. PLK1-mediated phosphorylation at Ser-179 is essential for its localization in the nuclear envelope and promotes its dissociation from microtubules during early mitosis and positively regulates nuclear envelope breakdown during prophase.|||The CAP-Gly domain is essential for interactions with microtubules and its binding partners and for its motion along the microtubules. Essential for its preferential binding to tyrosinated microtubules and for promoting the sustained interaction of the dynein motor with microtubules.|||Ubiquitinated by a SCF complex containing FBXL5, leading to its degradation by the proteasome.|||cell cortex|||centriole|||centrosome|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Aga ^@ http://purl.uniprot.org/uniprot/A2RSS6|||http://purl.uniprot.org/uniprot/B7ZNK6|||http://purl.uniprot.org/uniprot/Q64191 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Ntn-hydrolase family.|||Cleaved into an alpha and beta chain by autocatalysis; this activates the enzyme (PubMed:8586423). The N-terminal residue of the beta subunit is responsible for the nucleophile hydrolase activity.|||Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins.|||Heterotetramer of two alpha and two beta chains arranged as a dimer of alpha/beta heterodimers.|||Lysosome|||N-glycosylated. http://togogenome.org/gene/10090:Cfap107 ^@ http://purl.uniprot.org/uniprot/Q4KKZ1 ^@ Function|||Subcellular Location Annotation ^@ Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Ubl5 ^@ http://purl.uniprot.org/uniprot/Q9EPV8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CLK1, CLK3 and CLK4. Interacts with coilin/COIL. Interacts with spliceosome components SART1 and EFTUD2. Intracts with FANCI; this interaction promotes FANCI dimerization.|||Nucleus|||Ubiquitin-like protein that plays a role in cell proliferation and sister chromatid cohesion by associating with spliceosomal proteins. Participates thereby in pre-mRNA splicing by maintaining spliceosome integrity. Promotes the functional integrity of the Fanconi anemia DNA repair pathway by interacting with FANCI component and subsequently mediating the formation of FANCI homodimers. Plays also a protective role against ER stress-induced apoptosis. http://togogenome.org/gene/10090:Or4c108 ^@ http://purl.uniprot.org/uniprot/A2ATG2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem141 ^@ http://purl.uniprot.org/uniprot/A2AJB2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM141 family.|||Membrane http://togogenome.org/gene/10090:Tgm1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J293|||http://purl.uniprot.org/uniprot/Q9JLF6 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 1 Ca(2+) ion per subunit.|||Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Responsible for cross-linking epidermal proteins during formation of the stratum corneum. Involved in cell proliferation (By similarity).|||Expressed in large amounts in epithelial tissues (lung, liver and kidney).|||Interacts with PLAAT4.|||Membrane|||Palmitoylated.|||The membrane anchorage region possesses a cluster of five cysteines within which fatty acid(s) may become thioester-linked. It is subject to phorbol ester-stimulated phosphorylation and is hypersensitive to proteolysis, which releases the enzyme in a soluble form.|||Tyrosine-phosphorylated. http://togogenome.org/gene/10090:Cox17 ^@ http://purl.uniprot.org/uniprot/P56394|||http://purl.uniprot.org/uniprot/Q54AC6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COX17 family.|||Copper metallochaperone essential for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase. Binds two copper ions and delivers them to the metallochaperone SCO1 which transports the copper ions to the Cu(A) site on the cytochrome c oxidase subunit II (MT-CO2/COX2).|||Cytoplasm|||Interacts with COA1. Interacts with the chaperone CHCHD4; this is important for correct folding and the formation of disulfide bonds that stabilize the structure.|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Tuba3b ^@ http://purl.uniprot.org/uniprot/P05214|||http://purl.uniprot.org/uniprot/Q5FW91 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.|||Alpha-3 and alpha-7 are identical but coded by two different genes, they are testis-specific.|||Belongs to the tubulin family.|||Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488).|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.|||Nitration of Tyr-450 is irreversible and interferes with normal dynein intracellular distribution.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREC motif may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).|||Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.|||cytoskeleton http://togogenome.org/gene/10090:Hivep3 ^@ http://purl.uniprot.org/uniprot/A2A884 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in macrophages, lymphocytes, brain, thymus, spleen and bone marrow. Expressed in osteoblasts, whole bone and, to a lesser extent, in osteoclasts.|||Expressed in the thymus with increasing level, approximately 4-fold, from 15.5 dpc to 16.5 dpc, constant level from 16.5 dpc to birth, then decrease to a low level by P30. Expressed at 13.5 dpc in the dorsal root ganglia of the peripheral nervous system and the trigeminal ganglion of the metencephalon and at relatively low levels in the cerebral cortex; no significant expression was observed prior to 13.5 dpc. Expressed in the spinal cord at 19 dpc, but weakly detected in the lung and the liver.|||Hivep3 gene expression is probably controlled by a combination of differential promoter usage, alternative splicing, and possible intergenic splicing.|||Interacts with TRAF1 and TRAF2 as well as with JUN. Forms a multimeric complex with RUNX2 and E3 ubiquitin ligase WWP1.|||Mice display adult-onset osteosclerosis with increased bone mass due to increased osteoblast activity; the osteoblasts contain elevated levels of Runx2.|||Nucleus|||Phosphorylated on threonine and serine residues. Phosphorylation by cyclin-dependent kinase CDK1 decreases HIVEP3 DNA binding affinity, and by epidermal growth factor receptor kinase increases its DNA binding affinity.|||Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Binds also to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-alpha-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and pro-inflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation.|||Upon CD3/CD28 stimulation in CD4 T-cells. Induced by LPS in pre-B-cells.|||ZAS2 domain binds DNA as dimers, tetramers, and multiple of tetramers and readily forms highly ordered DNA-protein structures. http://togogenome.org/gene/10090:Tspan33 ^@ http://purl.uniprot.org/uniprot/Q8R3S2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Cytoplasm|||Homodimer; disulfide-linked (PubMed:17158226). Interacts (via extracellular domain) with ADAM10 (via extracellular domain) (PubMed:30463011). Interacts (via cytoplasmic domain) with PLEKHA7 (via WW domains); the interaction is dependent on PDZD11 being bound to PLEKHA7 and facilitates the docking of ADAM10 to zonula adherens (PubMed:30463011).|||Plays an important role in normal erythropoiesis (PubMed:17158226). It has a role in the differentiation of erythroid progenitors (PubMed:17158226). Regulates maturation and trafficking of the transmembrane metalloprotease ADAM10 (PubMed:23035126, PubMed:30463011). Negatively regulates ligand-induced Notch activity probably by regulating ADAM10 activity (By similarity). Mediates docking of ADAM10 to zonula adherens by interacting with ADAM10 and, in a PDZD11-dependent manner, with the zonula adherens protein PLEKHA7 (PubMed:30463011).|||Predominantly expressed in erythroblasts.|||adherens junction http://togogenome.org/gene/10090:Dok6 ^@ http://purl.uniprot.org/uniprot/Q2MHE5 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the DOK family. Type B subfamily.|||DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK6 promotes Ret-mediated neurite growth. May have a role in brain development and/or maintenance (By similarity).|||Interacts via its PTB domain with phosphorylated RET.|||On Ret activation, phosphorylated on one or more C-terminal tyrosine residues by an Src family kinase.|||PTB domain mediates receptor interaction. http://togogenome.org/gene/10090:Nmbr ^@ http://purl.uniprot.org/uniprot/O54799|||http://purl.uniprot.org/uniprot/Q0VEH1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||During osteoclast development, expression is abundant in early osteoclast precursor cells, decreases as the cells differentiate and is almost absent in mature osteoclasts.|||Expressed in a subset of neurons of the pre-Botzinger complex (PubMed:26855425). Within the pre-Botzinger complex, there is some overlap with neurons expressing Grpr with some cells expressing only Grpr or Nmbr while some cells express both (PubMed:26855425). Expressed in dorsal root ganglion neurons and mast cells (PubMed:30734045). Expressed in lung (PubMed:31601264).|||Membrane|||Receptor for neuromedin-B (By similarity). Contributes to the maintenance of basal sigh rate through signaling in the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity (PubMed:26855425). Contributes to the induction of sneezing following exposure to chemical irritants or allergens which causes release of NMB by nasal sensory neurons and activation of NMBR-expressing neurons in the sneeze-evoking region of the brainstem (PubMed:34133943). These in turn activate neurons of the caudal ventral respiratory group, giving rise to the sneezing response (PubMed:34133943). Contributes to induction of acute itch, possibly through its activation on dorsal root ganglion neurons by the NMB peptide (PubMed:30734045). Plays a role in the innate immune response to influenza A virus infection by enhancing interferon alpha expression and reducing expression of IL6 (PubMed:31601264). Plays a role in CSF1-induced proliferation of osteoclast precursors by contributing to the positive regulation of the expression of the CSF1 receptor CSF1R (PubMed:28780306).|||Reduction in rate of basal sighing without affecting the respiratory rate (PubMed:26855425). Significantly reduced sneezing responses to chemical and allergen stimuli (PubMed:34133943).|||Up-regulated in lung tissue in response to infection with influenza A virus. http://togogenome.org/gene/10090:Lepr ^@ http://purl.uniprot.org/uniprot/P48356|||http://purl.uniprot.org/uniprot/Q3UNU8|||http://purl.uniprot.org/uniprot/Q3US58 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antagonizes Isoform A and isoform B-mediated LEP binding and endocytosis.|||Basolateral cell membrane|||Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Cell membrane|||Isoform A: highest level of expression in lung and kidney, also present in heart, brain, spleen, liver, muscle, choroid plexus and hypothalamus. Isoform B: highest levels of expression in hypothalamus and lower levels in brain, testes and adipose tissue. Expressed by neurons of the parabrachial nucleus (PubMed:25383904). Expressed by peripheral blood mononuclear cells and CD4(+) T-cells (PubMed:9732873). Isoform E: expressed in adipose tissue, liver, hypothalamus, cerebral microvessels, heart, and testes (PubMed:17620316).|||Lateral cell membrane|||May transport LEP across the blood-brain barrier. Binds LEP and mediates LEP endocytosis (PubMed:17620316, PubMed:20223942). Does not induce phosphorylation of and activate STAT3 (PubMed:11923481, PubMed:20223942).|||Membrane|||Mutants are hyperphagic, obese, infertile, diabetic and have impaired growth (PubMed:12594516). Have wet brain weight significantly lower than controls. Brain uptake of leptin is also reduced (PubMed:11861497). Animals have an increased bone formation leading to high bone mass (PubMed:10660043). Have impaired T-cell immunity, Th2 responses are favoured in mutants (PubMed:9732873). Conditional knockout in parabrachial nucleus CCK-expressing neurons, treated with 2-deoxyglucose, have increased levels of glucagon, corticosterone and epinephrin concentrations compared to wild-types (PubMed:25383904).|||On ligand binding, phosphorylated on two conserved C-terminal tyrosine residues (isoform B only) by JAK2. Tyr-985 is required for complete binding and activation of PTPN11, ERK/FOS activation,for interaction with SOCS3 and SOCS3 mediated inhibition of leptin signaling. Phosphorylation on Tyr-1138 is required for STAT3 binding/activation. Phosphorylation of Tyr-1077 has a more accessory role.|||Present as a mixture of monomers and dimers (Probable). The phosphorylated receptor binds a number of SH2 domain-containing proteins such as JAK2, STAT3, PTPN11, and SOCS3 (By similarity) (PubMed:11018044, PubMed:11923481). Interaction with SOCS3 inhibits JAK/STAT signaling and MAPK cascade (PubMed:11018044).|||Receptor for hormone LEP/leptin (Probable) (PubMed:11861497). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS (PubMed:10799542, PubMed:25383904, PubMed:11923481, PubMed:11861497). In the hypothalamus, LEP acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (PubMed:10660043, PubMed:12594516). In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic and affects innate and adaptive immunity (PubMed:25383904, PubMed:11923481). Control of energy homeostasis and melanocortin production (stimulation of POMC and full repression of AgRP transcription) is mediated by STAT3 signaling, whereas distinct signals regulate NPY and the control of fertility, growth and glucose homeostasis (PubMed:12594516). Involved in the regulation of counter-regulatory response to hypoglycemia by inhibiting neurons of the parabrachial nucleus (PubMed:25383904). Has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T-cells. Leptin increases Th1 and suppresses Th2 cytokine production (PubMed:9732873).|||Secreted|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Col7a1 ^@ http://purl.uniprot.org/uniprot/Q63870 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homotrimer. Interacts with MIA3/TANGO1; facilitating its loading into transport carriers and subsequent secretion (By similarity).|||Mice do not express type VII collagen in their skin; they are born with extensive cutaneous blistering and die during the first two weeks of life, possibly because of complications arising from blistering; this mouse mutant resembles the autosomal recessive inherited form of the dystrophic epidermolysis bullosa (DEB) in humans. Heterozygotes by comparison display a normal phenotype.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen.|||Transcription of COL7A1 is stimulated by TGFB1 in keratinocytes and this is possibly dependent on a putative interaction between SMADS and AP1.|||basement membrane http://togogenome.org/gene/10090:Top2b ^@ http://purl.uniprot.org/uniprot/Q64511 ^@ Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II topoisomerase family.|||Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+).|||Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.|||Homodimer (By similarity). Interacts with KIAA1210 (PubMed:28203736). Interacts with PLSCR1 (By similarity).|||Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation.|||Knockout animals have B-cell developmental defects affecting multiple stages of development likely due to transcriptional defects. These mutant mice have altered splenic follicle structure with reduce marginal zone and follicular B-cell zones; immunophenotyping show decreased B- cells at all stages of development. Mutant mice fail to mount an antibody response to vaccination and B-cells fail to proliferate in response to stimulation, indicating deficits in B-cell function.|||Nucleus|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Arhgap1 ^@ http://purl.uniprot.org/uniprot/Q5FWK3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. Interacts with BNIPL (By similarity).|||GTPase activator for the Rho, Rac and Cdc42 proteins, converting them to the putatively inactive GDP-bound state. Cdc42 seems to be the preferred substrate (By similarity). http://togogenome.org/gene/10090:H2ac10 ^@ http://purl.uniprot.org/uniprot/Q8CGP5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Deiminated on Arg-4 in granulocytes upon calcium entry.|||Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.|||Nucleus|||Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.|||Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Or4n4 ^@ http://purl.uniprot.org/uniprot/Q8VFT5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r235 ^@ http://purl.uniprot.org/uniprot/Q8R297 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cobl ^@ http://purl.uniprot.org/uniprot/Q5NBX1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Detected in brain cortex and in the Purkinje cell layer in the cerebellum. Detected in hippocampus neurons, and at lower levels in testis, lung and spleen (at protein level). Detected in embryonic neural tube.|||Identified in a complex composed of COBL, PACSIN1 and WASL. Interacts with PACSIN1, PACSIN2 and PACSIN3 (By similarity). Identified in a complex composed of ACTA1, COBL, GSN and TMSB4X. Interacts (via WH2 domains) with actin monomers. Interacts with DBNL.|||Plays an important role in the reorganization of the actin cytoskeleton. Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells.|||cytoskeleton|||ruffle http://togogenome.org/gene/10090:Or10g3 ^@ http://purl.uniprot.org/uniprot/Q8VF72 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Apob ^@ http://purl.uniprot.org/uniprot/E9Q414 ^@ Function|||PTM|||RNA Editing|||Subcellular Location Annotation|||Subunit ^@ Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor.|||Cytoplasm|||Interacts with PCSK9 (By similarity). Interacts with MTTP (By similarity). Interacts with AUP1 (By similarity). Interacts with CIDEB (PubMed:19187774, PubMed:23297397).|||Lipid droplet|||Palmitoylated; structural requirement for proper assembly of the hydrophobic core of the lipoprotein particle.|||Secreted|||The stop codon (UAA) at position 2179 is created by an APOBEC1-containing mRNA editing complex. Apo B-48, derived from the fully edited RNA, is produced only in the intestine and is found in chylomicrons. Apo B-48 is a shortened form of apo B-100 which lacks the LDL-receptor region. The unedited version (apo B-100) is produced by the liver and is found in the VLDL and LDL (By similarity). http://togogenome.org/gene/10090:Miip ^@ http://purl.uniprot.org/uniprot/A2A7Y5 ^@ Caution|||Function|||Sequence Caution|||Subunit ^@ Inhibits glioma cells invasion and down-regulates adhesion- and motility-associated genes such as NFKB2 and ICAM1. Exhibits opposing effects to IGFBP2 on cell invasion (By similarity).|||Interacts with IGFBP2.|||Intron retention.|||It is uncertain whether Met-1 or Met-4 is the initiator. http://togogenome.org/gene/10090:Efhc1 ^@ http://purl.uniprot.org/uniprot/B2CKC6|||http://purl.uniprot.org/uniprot/Q9D9T8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in adult brain including hippocampus, cerebellum, cerebral cortex, thalamus, hypothalamus, amygdala and upper brainstem. Expressed in soma and dentrites of pyramidal neurons of the hippocampal CA1 region, pyramidal neurons of the cerebral cortex and Purkinje cells of cerebellum. Highly expressed in testis, trachea, and oviduct, moderately in lung, and slightly in brain. Highly expressed in sperm flagella and tracheal cilia (at protein level).|||Interacts with the C-terminus of CACNA1E. InteractS with alpha-tubulin.|||Microtubule-associated protein which regulates cell division and neuronal migration during cortical development. Necessary for mitotic spindle organization. Necessary for radial and tangential cell migration during brain development, possibly acting as a regulator of cell morphology and process formation during migration (By similarity). May enhance calcium influx through CACNA1E and stimulate programmed cell death. Overexpression of EFHC1 in hippocampal primary culture neurons induced apoptosis (PubMed:15258581). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity).|||centrosome|||cilium axoneme|||spindle|||spindle pole http://togogenome.org/gene/10090:Mageb18 ^@ http://purl.uniprot.org/uniprot/Q8BQR7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis, stomach, large intestine, small intestine, spleen, lymph node, bone marrow lymphocytes and blood T-lymphocytes. Not detected in brain, heart, lung, liver or kidney (at protein level).|||In the testis, expression is detected from the first day of birth, increases steadily in the first 3 weeks of life, decreases around day 28, increases at day 35 and is stable between 35 and 56 days. Highly expressed in spermatogonia and is also observed in primary and secondary spermatocytes but less so in spermatids (at protein level).|||Interacts with LNX1.|||May enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. http://togogenome.org/gene/10090:Nr1h2 ^@ http://purl.uniprot.org/uniprot/Q60644|||http://purl.uniprot.org/uniprot/Q8BP65 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Forms a heterodimer with RXR. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts (when sumoylated) with GPS2; interaction with GPS2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (By similarity). Interacts with ABCA12 and ABCA1; this interaction is required for ABCA1 localization to the cell surface and is necessary for its normal activity and stability (By similarity).|||Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:18055760, PubMed:19520913, PubMed:20427281). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4) (PubMed:18055760, PubMed:19520913, PubMed:20427281). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8 (PubMed:18055760, PubMed:19520913, PubMed:20427281). Interplays functionally with RORA for the regulation of genes involved in liver metabolism (PubMed:18055760, PubMed:19520913, PubMed:20427281, PubMed:24206663, PubMed:28846071). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (PubMed:28846071, PubMed:25806685). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (PubMed:25806685). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (PubMed:24206663). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (By similarity).|||Nucleus|||Sumoylated by SUMO2 at Lys-395 and Lys-433 during the hepatic acute phase response, leading to promote interaction with GPS2 and prevent N-Cor corepressor complex dissociation.|||Ubiquitous. http://togogenome.org/gene/10090:Sgo2b ^@ http://purl.uniprot.org/uniprot/J3QMK1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the shugoshin family.|||centromere http://togogenome.org/gene/10090:Fat3 ^@ http://purl.uniprot.org/uniprot/E9QK16 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Xpnpep2 ^@ http://purl.uniprot.org/uniprot/B1AVD1|||http://purl.uniprot.org/uniprot/B1AVD2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M24B family.|||Cell membrane|||Expressed in embryos from 7 days onwards, with highest expression at 15 days.|||Homotrimer.|||Membrane-bound metalloprotease which catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro. May play a role in the metabolism of the vasodilator bradykinin.|||N-glycosylated.|||Strongly expressed in small intestine, heart and lung. Also detected in testis, skeletal muscle, spleen, liver, kidney, brain, uterus, eye, lymph node, thymus, stomach, prostate and bone marrow. http://togogenome.org/gene/10090:Cldn23 ^@ http://purl.uniprot.org/uniprot/Q3ULX4|||http://purl.uniprot.org/uniprot/Q9D7D7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Lcmt2 ^@ http://purl.uniprot.org/uniprot/Q8BYR1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the methyltransferase superfamily. LCMT family.|||Interacts with RNF144B/IBRDC2.|||Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA (By similarity). May methylate the carboxyl group of leucine residues to form alpha-leucine ester residues. http://togogenome.org/gene/10090:Lmod1 ^@ http://purl.uniprot.org/uniprot/F8VPR1|||http://purl.uniprot.org/uniprot/Q8BVA4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the tropomodulin family.|||Detected in aorta, urinary bladder and uterus (at protein level). Detected in smooth muscle cells. Detected in aorta, bladder, colon, intestine, stomach and uterus.|||Required for proper contractility of visceral smooth muscle cells (PubMed:28292896). Mediates nucleation of actin filaments (By similarity).|||cytoskeleton|||sarcomere http://togogenome.org/gene/10090:Plppr3 ^@ http://purl.uniprot.org/uniprot/A0A0R3P9D0|||http://purl.uniprot.org/uniprot/E9QAX3|||http://purl.uniprot.org/uniprot/Q7TPB0 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Has most probably no phospholipid phosphatase activity (By similarity). This is supported by the fact that the phosphatase sequence motifs as well as the His residue acting as a nucleophile in active phosphatases of the PA-phosphatase related phosphoesterase family are not conserved (By similarity).|||Membrane http://togogenome.org/gene/10090:Ncoa5 ^@ http://purl.uniprot.org/uniprot/Q91W39 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds HTATIP2/TIP30. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and PPP1CA (By similarity).|||Contains one Leu-Xaa-Xaa-Leu-Leu (LxxLL) motif that is essential for the association with nuclear receptors.|||Expressed in both unfertilized and fertilized eggs during preimplantation development (at protein level) (PubMed:24268775). Detected in all blastmeres of morulae at 3 days post-coitum (dpc) (at protein level) (PubMed:24268775). Localizes to the pluripotent inner cell mass (ICM) of blastocysts at 4 dpc (at protein level) (PubMed:24268775). Expressed in many fetal tissues (PubMed:11113208). High expression in fetal heart and kidney (PubMed:11113208). Weak expression in fetal liver (PubMed:11113208).|||Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) of the ESR receptors, and with the orphan nuclear receptor NR1D2. Involved in the coactivation of nuclear steroid receptors (ER) as well as the corepression of MYC in response to 17-beta-estradiol (E2) (By similarity).|||Nucleus http://togogenome.org/gene/10090:Slc7a13 ^@ http://purl.uniprot.org/uniprot/Q91WN3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Associates with SLC3A1/rBAT to form a functional heterodimeric complex that transports anionic and neutral amino acids across the apical plasma membrane of renal epithelium. Preferentially mediates exchange transport, but can also operate via facilitated diffusion. May act as a major transporter for L-cystine in late proximal tubules, ensuring its reabsorption from the luminal fluid in exchange for cytosolic L-glutamate or L-aspartate.|||Belongs to the amino acid-polyamine-organocation (APC) superfamily.|||Disulfide-linked heterodimer composed of the catalytic light subunit SLC7A13 and the heavy subunit SLC3A1.|||Expressed in renal tubules in the outer stripe of the outer medulla and medullary ray (at protein level). Detected in male but not in female kidney. http://togogenome.org/gene/10090:Brf1 ^@ http://purl.uniprot.org/uniprot/G3X8S2 ^@ Similarity ^@ Belongs to the TFIIB family. http://togogenome.org/gene/10090:Ltbp3 ^@ http://purl.uniprot.org/uniprot/Q61810 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 8.5-9.0 dpc highly expressed in liver. Significant expression was also seen in the developing central nervous, somites and cardiovascular tissue. At 13.5-16.5 dpc expression was seen in osteoblasts, respiratory epithelial cells, and nephrons and dermal connective tissue.|||Belongs to the LTBP family.|||Contains hydroxylated asparagine residues.|||Forms part of the large latent transforming growth factor beta (TGFB1) precursor complex; removal is essential for activation of complex. Interacts with EFEMP2 (By similarity).|||Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta.|||Secreted|||Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Tgm2 ^@ http://purl.uniprot.org/uniprot/P21981 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites. In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form. In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity.|||Auto-transglutaminated: Forms covalent cross-links mediated by transglutaminase between Gln-632 and the epsilon-amino group of a lysine residue of itself or HMGB1, forming homopolymers and heteropolymers, respectively.|||Belongs to the transglutaminase superfamily. Transglutaminase family.|||Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively (By similarity). Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis (By similarity). Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:11274171, PubMed:11113189, PubMed:20489165). Under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses (By similarity). When secreted, catalyzes cross-linking of proteins of the extracellular matrix, such as FN1 and SPP1 resulting in the formation of scaffolds (By similarity). Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components (PubMed:12810961, PubMed:15905580). In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (PubMed:32116663). Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity). Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3 (By similarity). Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription (By similarity). Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system (By similarity). Regulates vein remodeling by mediating serotonylation and subsequent inactivation of ATP2A2/SERCA2 (PubMed:32116663). Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate (By similarity). Catalyzes specific deamidation of protein gliadin, a component of wheat gluten in the diet (By similarity). May also act as an isopeptidase cleaving the previously formed cross-links (By similarity). Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (PubMed:11274171).|||Cell membrane|||Chromosome|||Disulfide bond formation inactivates the calcium-dependent acyltransferase activity. Cys-370 can form disulfide bonds with both Cys-230 and Cys-371: formation of a disulfide bond between Cys-230 and Cys-370 facilitates formation of the disulfide between Cys-370 and Cys-371, which promotes inactivation of the acyltransferase activity. May also form interchain disulfids between Cys-230 and Cys-370. Ca(2+) protects against disulfide bond formation and inactivation.|||Mitochondrion|||Monomer. Interacts with phospholipase C; promoting alpha-1 adrenergic receptor signaling (By similarity). Interacts with PLCD1 (By similarity).|||No visible phenotype in normal conditions (PubMed:11274171, PubMed:11113189). During apoptosis, mice display defective clearance of apoptotic cells in the thymus (PubMed:12810961). Moreover, inflammatory as well as autoimmune reactions develop spontaneously with age (PubMed:12810961). Defective clearance of apoptotic cells is caused by an impaired capacity of macrophages to engulf, but not to bind, apoptotic cells (PubMed:15905580). Mice also show glucose intolerance after intraperitoneal glucose loading: mice manifest a tendency to develop hypoglycemia after administration of exogenous insulin as a consequence of enhanced IRS2 phosphorylation (PubMed:12205028).|||Nucleus|||S-nitrosylated, leading to inactivation of the acyltransferase activity.|||cytosol|||extracellular matrix http://togogenome.org/gene/10090:Or6c212 ^@ http://purl.uniprot.org/uniprot/Q8VFI4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sfxn5 ^@ http://purl.uniprot.org/uniprot/Q925N0 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sideroflexin family.|||Expressed in liver and brain. Expressed in brown adipose tissue (PubMed:36334589).|||In brown adipose tissue, expression is induced by cold.|||Knockdown in brown adipose tissue attenuates whole-body thermogenic responses upon exposure to cold. Brown adipocytes show decreased glycerol-3-phosphate levels in mitochondria.|||Mitochondrial amino-acid transporter (By similarity). Transports citrate (By similarity). Does not act as a serine transporter: not able to mediate transport of serine into mitochondria (By similarity). In brown adipose tissue, plays a role in the regulation of UCP1-dependent thermogenesis probably by supporting mitochondrial glycerol-3-phosphate utilization (PubMed:36334589).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ngfr ^@ http://purl.uniprot.org/uniprot/Q9Z0W1 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Binds to rabies virus glycoprotein Gs.|||(Microbial infection) Cell surface receptor for rabies virus glycoprotein Gs.|||Cell membrane|||Detected in Schwann cells (PubMed:11559852). Detected in embryonic brain, in hippocampus neurons (at protein level) (PubMed:22155786, PubMed:27457814). Detected in brain and spinal cord (PubMed:11559852).|||Detected in embryonic large blood vessels at 11.5 dpc.|||Does not bind NGF, BDNF, NTF3, and NTF4.|||Embryos are present at the expected Mendelian rate at 15.5 dpc, but mutant mice display about 40% perinatal lethality. At 11.5 dpc, mutant embryos display mildly to severely dilated blood vessels with thinner walls. The dorsal aorta is particularly affected. Many embryos show massive dilatations, ruptures and blood leakage. Surviving animals display small size and hind limb ataxia at 13 days after birth. When held by their tails, they respond by stretching their hind legs pointing upwards. The diameter of their sciatic nerve is strongly reduced. At 3 days after birth, the number of Schwann cells is strongly reduced in sciatic nerve from mutant mice. Likewise, the number of sensory neurons in dorsal root ganglia is strongly reduced (PubMed:11559852). The initially reported gene disruption experiment finds that mice are born at the expected Mendelian rate, are fertile, and have no visible phenotype when young. However, after 4 months mutant mice develop skin alterations with severe ulcers on all extremities. Already before the onset of symptoms, mutant mice display decreased skin innervation and smaller dorsal root ganglia, plus impaired heat sensitivity (PubMed:11559852).|||Expression oscillates in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain and in liver. Expression seen at higher levels during the light period and lower during the dark period.|||Homodimer; disulfide-linked. Heterodimer with SORCS2 (PubMed:22155786, PubMed:24908487, PubMed:27457814). The extracellular domains of the heterodimer bind NGF. The cytoplasmic region of the heterodimer binds TRIO. NGF binding mediates dissociation of TRIO from the receptor complex (PubMed:22155786). Interacts with TRAF2, TRAF4, TRAF6, PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1 which bridges NGFR to NTRK1. Interacts with BEX1 (By similarity). Interacts with BEX3 (PubMed:11830582). Interacts with KIDINS220 and NTRK1. Can form a ternary complex with NTRK1 and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1. Interacts (via death domain) with RAB31 (PubMed:22460790). Interacts with NTRK2; may regulate the ligand specificity of the NTRK2 receptor (PubMed:11559852). Interacts with LINGO1. Interacts with NRADD. Interacts with MAGED1; the interaction antagonizes the association NGFR:NTRK1 (By similarity). Interacts with RTN4R (PubMed:22923615). Interacts (via death domain) with ARHGDIA and RIPK2 (By similarity).|||Low affinity neurotrophin receptor which can bind to mature NGF, BDNF, NTF3, and NTF4 (PubMed:11559852, PubMed:1317267). Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF (proNGF), BDNF (proBDNF) and NTF3 (proNT3) with high affinity, and has much lower affinity for mature NGF and BDNF (PubMed:22155786, PubMed:24908487, PubMed:27457814). Plays an important role in differentiation and survival of specific neuronal populations during development (PubMed:1317267, PubMed:11559852). Can mediate cell survival as well as cell death of neural cells (PubMed:1317267, PubMed:11559852, PubMed:24908487). The heterodimeric receptor formed with SORCS2 plays a role in proBDNF-dependent synaptic plasticity, in hippocampal long term depression (LTD) and long term potentiation (LTP) (PubMed:27457814). Plays a role in the inactivation of RHOA (By similarity). Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (PubMed:22460790). Necessary for the circadian oscillation of the clock genes BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver (PubMed:23785138).|||Minor isoform that lacks exon 3.|||N-glycosylated (PubMed:11559852). O-glycosylated.|||Perikaryon|||Phosphorylated on serine residues.|||The death domain mediates interaction with RANBP9 (By similarity). It also mediates interaction with ARHGDIA and RIPK2 (By similarity).|||The extracellular domain is responsible for interaction with NTRK1.|||The initial gene disruption experiment found a less pronounced phenotype than that reported in a later study (PubMed:1317267, PubMed:11559852). Both experiments disrupt expression of isoform 1 and NGF binding (PubMed:1317267, PubMed:11559852). The differences may be due to the presence of isoform 2; its expression is disrupted in the later experiment, but not in the initial experiment (PubMed:11559852).|||dendritic spine|||growth cone http://togogenome.org/gene/10090:Zfp653 ^@ http://purl.uniprot.org/uniprot/Q6YND2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Highly expressed in testis and spleen. Moderately expressed in lung, adrenal gland, uterus, and ovary. Very low expression in pancreas, heart, skeletal muscle, adipose tissue, kidney, and liver.|||Interacts with NR5A1.|||Nucleus|||Transcriptional repressor. May repress NR5A1, PPARG, NR1H3, NR4A2, ESR1 and NR3C1 transcriptional activity (By similarity). http://togogenome.org/gene/10090:Adpgk ^@ http://purl.uniprot.org/uniprot/Q8VDL4 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ADP-dependent glucokinase family.|||Binds 1 Mg(2+) ion per subunit.|||Catalyzes the phosphorylation of D-glucose to D-glucose 6-phosphate using ADP as the phosphate donor. GDP and CDP can replace ADP, but with reduced efficiency.|||Monomer.|||Secreted http://togogenome.org/gene/10090:9930111J21Rik1 ^@ http://purl.uniprot.org/uniprot/Q5SVP0 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Or2y1d ^@ http://purl.uniprot.org/uniprot/Q8VGX0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rab33a ^@ http://purl.uniprot.org/uniprot/P97950|||http://purl.uniprot.org/uniprot/Q3SXA7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Expressed predominantly in brain. Weak expression in ovary. http://togogenome.org/gene/10090:Abca9 ^@ http://purl.uniprot.org/uniprot/Q8K449 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCA family.|||Detected along the outer surface of the brain or along the fissure of cerebellar lobules at 13 dpc to P21.|||Down-regulated by digoxin.|||Highly expressed in heart and to lower extent in kidney, brain and spleen (PubMed:12532264). Weakly expressed in developing and adult brains (PubMed:29520568). Weakly expressed in the cerebellar granular layer at P14 and P21 (PubMed:29520568).|||Membrane|||Transporter that may play a role in monocyte differentiation and lipid transport and homeostasis. http://togogenome.org/gene/10090:Tmem218 ^@ http://purl.uniprot.org/uniprot/Q9CQ44 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM218 family.|||Diffuse renal cyst development with tubulointerstitial nephropathy and disruption of tubular basement membranes in essentially normal-sized kidneys. Retinal lesions characterized by slow-onset loss of photoreceptors.|||Interacts with TMEM67.|||May be involved in ciliary biogenesis or function.|||Membrane|||cilium http://togogenome.org/gene/10090:Or5p67 ^@ http://purl.uniprot.org/uniprot/Q8VFD1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Glipr1l1 ^@ http://purl.uniprot.org/uniprot/Q9DAG6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CRISP family.|||Cell membrane|||Detected at postnatal day 14 in developing testis (at protein level). Detected from postnatal day 18 onwards, with increasing levels through to postnatal day 36.|||Expressed in testis (at protein level). Little or no expression in other tissues tested.|||Membrane raft|||Mutants have normal number of pups per litter, body weight, testis weight and daily sperm production (PubMed:31672133). Mutant sperm have a significantly reduced ability to undergo the progesterone-induced acrosome reaction compared to wild type (PubMed:31672133).|||N-glycosylated (PubMed:20219979). N-glycosylation decreases during the transit in the caput.|||Part of a oolemmal binding multimeric complex (IZUMO1 complex) composed at least of IZUMO1 and GLIPR1L1; the complex assemblage is influenced by the maturation status of the male germ cell (PubMed:31672133). Interacts with IZUMO1 (PubMed:31672133).|||Required for optimal fertilization at the stage of sperm-oocyte fusion, plays a role in optimizing acrosome function, the translocation of IZUMO1 during the acrosome reaction and the fertilization process (PubMed:20219979, PubMed:31672133). Component of epididymosomes, one type of membranous microvesicules which mediate the transfer of lipids and proteins to spermatozoa plasma membrane during epididymal maturation. Also component of the CD9-positive microvesicules found in the cauda region.|||Secreted|||acrosome http://togogenome.org/gene/10090:S100a11 ^@ http://purl.uniprot.org/uniprot/P50543 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the S-100 family.|||Binds two calcium ions per molecule with an affinity similar to that of the S100 proteins.|||Cytoplasm|||Facilitates the differentiation and the cornification of keratinocytes.|||Homodimer; disulfide-linked.|||Nucleus|||Phosphorylation at Thr-5 significantly suppresses homodimerization and promotes association with NCL/nucleolin which induces nuclear translocation. http://togogenome.org/gene/10090:Bpifc ^@ http://purl.uniprot.org/uniprot/Q3V1D7|||http://purl.uniprot.org/uniprot/Q8C186 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||Monomer. Homodimer; disulfide-linked.|||Secreted|||The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues.|||The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested.|||The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope. http://togogenome.org/gene/10090:Artn ^@ http://purl.uniprot.org/uniprot/Q9Z0L2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family. GDNF subfamily.|||Homodimer; disulfide-linked (By similarity). Binds to RET.|||Ligand for the GFR-alpha-3-RET receptor complex but can also activate the GFR-alpha-1-RET receptor complex. Supports the survival of sensory and sympathetic peripheral neurons in culture and also supports the survival of dopaminergic neurons of the ventral mid-brain (By similarity). Strong attractant of gut hematopoietic cells thus promoting the formation Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue.|||Secreted http://togogenome.org/gene/10090:Cetn3 ^@ http://purl.uniprot.org/uniprot/O35648 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.|||Belongs to the centrin family.|||Monomer (By similarity). Component of the TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3.|||Nucleus envelope|||Plays a fundamental role in microtubule-organizing center structure and function.|||centriole|||centrosome|||nuclear pore complex|||nucleolus http://togogenome.org/gene/10090:Pfkl ^@ http://purl.uniprot.org/uniprot/P12382 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation (By similarity).|||Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E' sub-subfamily.|||Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis (By similarity). Negatively regulates the phagocyte oxidative burst in response to bacterial infection by controlling cellular NADPH biosynthesis and NADPH oxidase-derived reactive oxygen species. Upon macrophage activation, drives the metabolic switch toward glycolysis, thus preventing glucose turnover that produces NADPH via pentose phosphate pathway (PubMed:26194095).|||Cytoplasm|||GlcNAcylation at Ser-529 by OGT decreases enzyme activity, leading to redirect glucose flux through the oxidative pentose phosphate pathway. Glycosylation is stimulated by both hypoxia and glucose deprivation (By similarity).|||Homo- and heterotetramers (By similarity). Phosphofructokinase (PFK) enzyme functions as a tetramer composed of different combinations of 3 types of subunits, called PFKM (M), PFKL (L) and PFKP (P). The composition of the PFK tetramer differs according to the tissue type it is present in. The kinetic and regulatory properties of the tetrameric enzyme are dependent on the subunit composition, hence can vary across tissues (Probable). http://togogenome.org/gene/10090:Capn8 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0K6|||http://purl.uniprot.org/uniprot/Q91VA3 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C2 family.|||Binds 2 calcium ions.|||Calcium-regulated non-lysosomal thiol-protease (By similarity). Involved in membrane trafficking in the gastric surface mucus cells (pit cells) and may involve the membrane trafficking of mucus cells via interactions with coat protein. Proteolytically cleaves the beta-subunit of coatomer complex.|||Cytoplasm|||Golgi apparatus|||Monomer and homooligomer. Interacts with COPS1/GPS1, COPB1, EYA2, NME2, NME4 and TOMM70.|||Predominantly expressed in the stomach. Localizes strictly to the surface mucus cells in the gastric epithelium and the mucus-secreting goblet cells in the duodenum.|||The concentration of calcium for half-maximal activity is 0.3 mM. Inhibited by calpastatin and calpeptin.|||The domain III mediates oligomerization.|||Undergoes autolytic cleavage between Ala-5 and Ala-6 which gives rise to fragments extending from Ala-6 to the C-terminus, Ala-6 to the EF-hand 2 domain and from Ala-6 to the beginning of domain III. http://togogenome.org/gene/10090:Slc31a1 ^@ http://purl.uniprot.org/uniprot/Q8K211 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||At E14.5, expressed in the forebrain, liver, nasal regions, and somites (PubMed:11391004). By E16.5, expression is ubiquitous, with high expression in the liver, intestine, somites, and choroid plexus (PubMed:11391004). By E18.5 expression is more restricted to the choroid plexus, kidney, intestine, and tooth buds (PubMed:11391004). Expressed principally by Sertoli cells (SCs) and the spermatocytes with the highest expression in the primary pachytene spermatocytes within seminiferous tubule stages II-VI (PubMed:31002737).|||Basolateral cell membrane|||Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.|||Cell membrane|||Early endosome membrane|||Expressed in the tubules in the inner cortex and inner medulla of the kidney, the villi of the small intestine, the choroid plexus of the brain, the stroma of the ovary, the seminiferous tubules of the testes, and the sclera of the eye (PubMed:11391004). Expressed in intestinal epithelial cells, with an increase expression from the crypt to the tip of the villus (PubMed:16950140). Mainly expressed in both proximal and distal tubular cells in kidneys (PubMed:19144690).|||Homotrimer; is stabilized by cisplatin via interactions between cisplatin and the Met motif, and could be crucial for the copper(2+) reduction process and copper(1+) stabilization. Heterotrimer between SLC31A1, CCS and SOD1; this heterotrimer is copper(1+)-mediated and its maintenance is regulated through SOD1 activation. Interacts with KDR; this interaction is induced upon VEGFA stimulation leading to SLC31A1 and KDR subsequent co-internalization to early endosomes, thereby activating KDR downstream signaling in endothelial cells. Interacts (via C-terminal domain) with ATOX1 (via dimer form); this interaction improves ATOX1 stability and controls intracellular copper(1+) levels (By similarity). Interacts with SLC31A2; this interaction stabilizes SLC31A2 and protects its from ubiquitination and degradation (PubMed:24167251). Interacts (via C-terminal domain) with CCS; this interaction is copper(1+)-mediated (By similarity).|||Homozygous mice lacking Slc31a1 exhibit profound growth and developmental defects and die in utero in mid-gestation (PubMed:11391005, PubMed:11391004). Homozygous embryos exhibit a dramatic reduction in size at E7.5, which is exacerbated during the progression of in utero development through day E10.5 (PubMed:11391005). Although the fundamental mouse embryonic structures are conserved at E7.5, homozygous embryos show that many structures including the neural ectoderm and mesoderm cell layers are poorly developed (PubMed:11391005). Conditionnal knockout mice lacking Slc31a1 in intestinal epithelial cells, are born at the expected frequency and exhibit normal growth rate and mass for the first 6-8 days postpartum, poor growth and lethality occurred beginning approximately 10 days after birth (PubMed:16950140). Conditionnal knockout mice lacking Slc31a1 in germ cells (GCs) seem normal in appearance (PubMed:31002737). Conditionnal knockout mice lacking Slc31a1 in Sertoli cells (SCs) exhibit normal fertility and display similar appearance as their wild-type littermates; no obvious behavioral deficit are noted (PubMed:31002737).|||Late endosome membrane|||Mobilizes copper(1+) out of the endosomal compartment, making copper(1+) available for export out of the cells.|||O-Glycosylation at Thr-34 protects from proteolytic cleavage in the N-terminal extracellular domain.|||Proteolytic cleavage, leading to a truncated form, is facilitated by SLC31A2 (PubMed:24167251) and initiated preferentially by CTSL and to a minor extend by CTSB in endolysosomal compartments (PubMed:27143361, PubMed:24167251). A post-CTSL/cathepsin L processing occurs to yield to the fully truncated form (PubMed:27143361).|||Recycling endosome membrane|||Sulfenylated at Cys-195 after stimulation with VEGFA, which induces SLC31A1-KDR disulfide bond formation and their co-internalization to early endosomes, driving to a sustained VEGFR2 signaling.|||The C-terminal domain mediates copper(1+) binding and is involved in the copper(1+)-dependent-ATOX1 interaction. The C-terminal domain appears to act to limit transport through the pore by regulating the rate of exit of copper ions at the intracellular side. The N-terminal domain can collect copper(2+) from copper(2+) carriers in blood. The N-terminal domain, in the trimeric arrangement, tunes its reactivity with copper, promoting copper(2+) reduction and copper(1+) stabilization. The bis-His motif directly coordinate to copper(2+).|||Uniporter that mediates the transport of copper(1+) from the extracellular space to the cytoplasm, across the plasma membrane (PubMed:11391005, PubMed:12177073, PubMed:16847145, PubMed:24167251). Then, delivers directly copper(1+) to specific chaperone such as ATOX1, via a copper(1+)- mediated transient interaction between the C-terminal domain and a copper(1+) chaperone, thus controlling intracellular copper(1+) levels (By similarity). May function in copper(1+) import from the apical membrane thus may drive intestinal copper absorption (PubMed:16950140). The copper(1+) transport mechanism is sodium-independent, saturable and of high-affinity (By similarity). Also mediates the uptake of silver(1+) (PubMed:20569931). May function in the influx of the platinum-containing chemotherapeutic agents (PubMed:16847145, PubMed:19144690, PubMed:12370430). The platinum-containing chemotherapeutic agents uptake is saturable (By similarity). Also participates in the first step of copper(2+) acquisition by cells through a direct transfer of copper(2+) from copper(2+) carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper(2+) reduction and probably followed by copper(1+) stabilization (By similarity). In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper(1+) transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-195 leading to a subsequent disulfide bond formation between SLC31A1 and KDR (PubMed:35027734). The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (By similarity). http://togogenome.org/gene/10090:Pbx1 ^@ http://purl.uniprot.org/uniprot/D9J2V6|||http://purl.uniprot.org/uniprot/P41778|||http://purl.uniprot.org/uniprot/Q71VB4 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) In complex with PREP1, binds to the 5'-TGATTGAC-3' consensus sequence in the U5 region of Moloney murine leukemia virus and promotes viral transcription.|||As part of a PDX1:PBX1b:MEIS2B complex in pancreatic acinar cells, is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element.|||Belongs to the TALE/PBX homeobox family.|||Conditional knockout in hematopoietic cells leads to a reduction in the number of natural killer cell-committed progenitors in bone marrow, decreases the number of natural killer cells in bone marrow and spleen and reduces NFIL3 expression in bone marrow and splenic natural killer cells.|||Expressed constitutively in natural killer cell precursors in bone marrow.|||Forms a heterodimer with MEIS1 which binds DNA (PubMed:9525891, PubMed:19799567). The PBX1-MEIS1 heterodimer binds a cAMP-responsive sequence in CYP17 (PubMed:9525891). It also binds a consensus region in the SOX3 promoter (PubMed:19799567). PBX1 forms heterotrimers with MEIS1 and a number of HOX proteins including HOXA9, HOXD4, HOXD9 and HOXD10 (PubMed:9315626, PubMed:10082572, PubMed:10523646, PubMed:12409300). Forms heterodimers with HOXA1, HOXA5, HOXB7 and HOXB8 which bind the 5'-TGATTGAT-3' consensus sequence (By similarity). Also forms heterodimers with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4 which bind the 5'-ATCAATCAA-3' consensus sequence (PubMed:7791786). Interacts with PBXIP1 (By similarity). Interacts with TLX1 (By similarity). Interacts with FOXC1 (By similarity). Interacts with MN1 (By similarity).|||Interacts with MEIS2 isoform Meis2D, SP1, SP3 and KLF4.|||Nucleus|||Part of a PDX1:PBX1b:MEIS2B complex; PBX1b recruits MEIS2B to the complex.|||The homeobox is required for PBX1 nuclear localization and for transcriptional activation of NFIL3.|||Transcription factor which binds the DNA sequence 5'-TGATTGAT-3' as part of a heterodimer with HOX proteins such as HOXA1, HOXA5, HOXB7 and HOXB8 (By similarity). Binds the DNA sequence 5'-TGATTGAC-3' in complex with a nuclear factor which is not a class I HOX protein (By similarity). Has also been shown to bind the DNA sequence 5'-ATCAATCAA-3' cooperatively with HOXA5, HOXB7, HOXB8, HOXC8 and HOXD4 (PubMed:7791786). Acts as a transcriptional activator of PF4 in complex with MEIS1 (By similarity). Also activates transcription of SOX3 in complex with MEIS1 by binding to the 5'-TGATTGAC-3' consensus sequence (PubMed:19799567). In natural killer cells, binds to the NFIL3 promoter and acts as a transcriptional activator of NFIL3, promoting natural killer cell development (PubMed:32190943). Plays a role in the cAMP-dependent regulation of CYP17A1 gene expression via its cAMP-regulatory sequence (CRS1) (PubMed:7913464). Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4 (By similarity). Acts as a transcriptional activator of NKX2-5 and a transcriptional repressor of CDKN2B (PubMed:22560297). Together with NKX2-5, required for spleen development through a mechanism that involves CDKN2B repression (PubMed:22560297). http://togogenome.org/gene/10090:Recql4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J3|||http://purl.uniprot.org/uniprot/Q75NR7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the helicase family. RecQ subfamily.|||Cytoplasm|||DNA-dependent ATPase (By similarity). May play a role in development of the palate and the limbs. May modulate chromosome segregation.|||Early embryonic lethality. Transgenic mice with exon 13-deleted RECQL4 are severely growth-retarded and show high (95%) perinatal lethality. They exhibit various skin, bone, intestine, tooth and thymus abnormalities and premature aging features, but have normal sensitivity to IR and UV irradiation. In contrast, transgenic mice expressing a truncated form of RECQL4 exhibit mild perinatal lethality, no growth defect, but show defects of the skin and skeleton, aneuploidy and increased cancer susceptibility.|||Interacts with UBR1 and UBR2. Interacts with MCM10; this interaction regulates RECQL4 unwinding activity (By similarity).|||Not expressed at 12.5 dpc. Expressed at 15.5 dpc-18.5 dpc, with highest levels in chondrocytes of developing bone and cartilage and immature proliferating enterocytes of intestine.|||Nucleus http://togogenome.org/gene/10090:Rnf25 ^@ http://purl.uniprot.org/uniprot/Q9QZR0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RNF25 family.|||Cytoplasm|||E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (By similarity). Catalyzes ubiquitination of RPS27A in response to ribosome collisions, promoting activation of RNF14 (By similarity). RNF25 catalyzes ubiquitination of other ribosomal proteins on stalled ribosomes, such as RPL0, RPL1, RPL12, RPS13 and RPS17 (By similarity). Also involved in ubiquitination and degradation of stalled ETF1/eRF1 (By similarity). Independently of its function in the response to stalled ribosomes, mediates ubiquitination and subsequent proteasomal degradation of NKD2 (PubMed:10500182, PubMed:18757723). May also stimulate transcription mediated by NF-kappa-B via its interaction with RELA/p65 (By similarity).|||Interacts with UBE2D2, and may also interact with UBE2E1 and UBE2E3 (PubMed:10500182). Interacts with RELA/p65 (By similarity).|||Ubiquitinated; autoubiquitinated.|||Ubiquitous. http://togogenome.org/gene/10090:Zkscan6 ^@ http://purl.uniprot.org/uniprot/Q810A1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Treml2 ^@ http://purl.uniprot.org/uniprot/Q2LA85 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cell surface receptor that may play a role in the innate and adaptive immune response. Acts as a counter-receptor for CD276 and interaction with CD276 on T-cells enhances T-cell activation (By similarity).|||Detected in B-lymphocytes and macrophages. Detected in spleen, lymph nodes, blood, bone marrow and cells from the peritoneal cavity (at protein level).|||Interacts with CD276 and this interaction enhances T-cell activation.|||Up-regulated in neutrophils and macrophages in response to bacterial lipopolysaccharide (LPS) and inflammatory stimuly. http://togogenome.org/gene/10090:Or2aa1 ^@ http://purl.uniprot.org/uniprot/Q8VF69 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fanci ^@ http://purl.uniprot.org/uniprot/Q8K368 ^@ Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Interacts with FANCD2; the interaction is direct. Interacts with FANCL. Interacts with MTMR15/FAN1. Interacts with POLN. Interacts with UBL5; the interaction promotes FANCI homodimerization.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Monoubiquitinated by FANCL on Lys-522 during S phase and upon genotoxic stress. Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the FANCA-FANCB-FANCC-FANCE-FANCF-FANCG-FANCM complex. Ubiquitination is required for binding to chromatin, DNA repair, and normal cell cycle progression. Monoubiquitination is stimulated by DNA-binding (By similarity).|||Nucleus|||Phosphorylated in response to DNA damage by ATM and/or ATR.|||Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage.|||The C-terminal 30 residues are probably required for function in DNA repair. http://togogenome.org/gene/10090:Dym ^@ http://purl.uniprot.org/uniprot/Q8CHY3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dymeclin family.|||Cytoplasm|||Golgi apparatus|||Interacts with GOLM1 and PPIB.|||Membrane|||Myristoylated in vitro; myristoylation is not essential for protein targeting to Golgi compartment.|||Necessary for correct organization of Golgi apparatus. Involved in bone development. http://togogenome.org/gene/10090:Angptl7 ^@ http://purl.uniprot.org/uniprot/Q8R1Q3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Has a role in the formation and organization of the extracellular matrix. In the eye, it functions as a mediator of dexamethasone-induced matrix deposition in the trabecular meshwork, the tissue responsible for the outflow of the ocular aqueous humor and for the maintenance of intraocular pressure (By similarity). Is a negative regulator of angiogenesis in the cornea, and plays a major role in maintaining corneal avascularity and transparency (PubMed:25622036).|||Homotetramer; disulfide-linked.|||Secreted http://togogenome.org/gene/10090:Golt1b ^@ http://purl.uniprot.org/uniprot/Q9CR60 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the GOT1 family.|||Golgi apparatus membrane|||May be involved in fusion of ER-derived transport vesicles with the Golgi complex. http://togogenome.org/gene/10090:Slc27a4 ^@ http://purl.uniprot.org/uniprot/Q91VE0 ^@ Disease Annotation|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Defects in Slc27a4 are the cause of wrinkle-free (wrfr) phenotype. It is a spontaneous, autosomal recessive mutation resulting in very tight, thick skin and is secondary characterized by severe breathing difficulties. Mice die shortly after birth. This phenotype is similar to human restrictive dermopathy, a very rare human genetic disorder.|||Deletion of Slc27a4 results in embryonic lethality, which has been attributed to a requirement for fat absorption early in embryonic development across the visceral endoderm.|||Endoplasmic reticulum membrane|||Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes (PubMed:10518211, PubMed:20448275). Appears to be the principal fatty acid transporter in small intestinal enterocytes (PubMed:20448275). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (By similarity). Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis (PubMed:11404000, PubMed:12821645, PubMed:15653672, PubMed:15699031). Probably involved in fatty acid transport across the blood barrier (By similarity). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones (PubMed:23407971).|||Most abundantly expressed in small intestine, brain, kidney, liver, skin and heart. In small intestine, expressed at high levels on the apical side of mature enterocytes. Highly expressed by the epithelial cells of the visceral endoderm and localized to the brush-border membrane of extraembryonic endodermal cells (at protein level). Expressed in the retinal pigment epithelium and in the retina (at protein level). Expressed in the retinal pigment epithelium and in the retina.|||Slc27a4 deficient mice display features of a neonatally lethal restrictive dermopathy. Their skin is characterized by hyperproliferative hyperkeratosis with a disturbed epidermal barrier, a flat dermal-epidermal junction, a reduced number of pilo-sebaceous structures, and a compact dermis. The rigid skin consistency results in an altered body shape with facial dysmorphia, generalized joint flexion contractures and impaired movement including suckling and breathing deficiencies. Lipid analysis demonstrates a disturbed fatty acid composition of epidermal ceramides, in particular a decrease in the C26:0 and C26:0-OH fatty acid substitutes. http://togogenome.org/gene/10090:Hnrnpa1 ^@ http://purl.uniprot.org/uniprot/P49312|||http://purl.uniprot.org/uniprot/Q5EBP8 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with SEPT6. Interacts with C9orf72. Interacts with KHDRBS1. Interacts with UBQLN2 (By similarity). Interacts with PPIA/CYPA (By similarity).|||Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1. May bind to specific miRNA hairpins.|||Nucleus|||Sumoylated. http://togogenome.org/gene/10090:Duoxa2 ^@ http://purl.uniprot.org/uniprot/Q9D311 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DUOXA family.|||Endoplasmic reticulum membrane|||Heterodimer with DUXA2; disulfide-linked (By similarity). Interacts with CSNK1G2 (By similarity).|||N-glycosylated.|||Required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX2. May play a role in thyroid hormone synthesis (By similarity). http://togogenome.org/gene/10090:Gm13306 ^@ http://purl.uniprot.org/uniprot/Q9Z1X0 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic factor that attracts skin-associated memory T-lymphocytes. May play a role in mediating homing of lymphocytes to cutaneous sites. May play a role in cell migration during embryogenesis. Nuclear forms may facilitate cellular migration by inducing cytoskeletal relaxation. Binds to CCR10.|||Expressed during development.|||Isoform 1 is predominantly expressed in placenta and weakly in skin. Isoform 2 is predominantly expressed in testes and brain, weakly in kidney and liver and even lower in heart and muscle. Low expression of both isoforms in other tissues.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Monomer, dimer, and tetramer. Heparin avidly promotes oligomerization. Interacts with TNFAIP6 (via Link domain).|||Nucleus|||Secreted http://togogenome.org/gene/10090:Spdye4a ^@ http://purl.uniprot.org/uniprot/A0A0G2JEI8|||http://purl.uniprot.org/uniprot/B9EIX3|||http://purl.uniprot.org/uniprot/Q5IBH6|||http://purl.uniprot.org/uniprot/Q9D5G0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Speedy/Ringo family.|||Interacts with CDK1. Does not interact with CDK2 in vivo.|||Nucleus|||Promotes progression through the cell cycle via binding and activation of CDK1.|||Testis-specific. http://togogenome.org/gene/10090:Brca1 ^@ http://purl.uniprot.org/uniprot/P48754|||http://purl.uniprot.org/uniprot/Q6NV63 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation.|||Chromosome|||Cytoplasm|||E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.|||Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1 (By similarity). Interacts with EXD2 (By similarity). Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme (By similarity).|||Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1. Interacts with EXD2. Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme.|||In the embryo, expressed in otic vesicles at day 9.5. At day 10.5, this expression decreases and high levels are found in the neuroectoderm. At days 11-12.5, high levels in differentiating keratinocytes and whisker pad primordia. At days 14-17, expression also observed in kidney epithelial cells. In the adult, highest levels found in spleen, thymus, lymph nodes, epithelial organs, and alveolar and ductal epithelial cells of the mammary gland. Very low levels in brain, kidney, and skin. No expression in heart, liver or lung.|||In the mammary gland, expression increases dramatically during pregnancy. Levels fall during lactation and increase again during post-lactational regression of the mammary gland.|||Nucleus|||Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-971 by CHEK2 regulates mitotic spindle assembly. Phosphorylation by AURKA regulates centrosomal microtubule nucleation.|||The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of ABRAXAS1, recruits BRCA1 at DNA damage sites.|||The RING-type zinc finger domain interacts with BAP1. http://togogenome.org/gene/10090:Zdhhc1 ^@ http://purl.uniprot.org/uniprot/Q8R0N9 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family.|||Endoplasmic reticulum membrane|||Endosome membrane|||Expressed at high levels in fetal lung and heart. Expressed at lower levels in fetal liver and brain. Also detected in adult islet cells of pancreas, Leydig cells of testis, retina and molecular layer of cerebellum.|||Golgi apparatus|||Has also a palmitoyltransferase activity-independent function in DNA virus-triggered and CGAS-mediated innate immune response (PubMed:25299331). Functions as an activator of STING1 by promoting its cGAMP-induced oligomerization and the recruitment of downstream signaling components (PubMed:25299331).|||Homozygous knockout mice are viable, fertile and do not display overt phenotype (PubMed:25299331). Composition and number of major immune cells is normal but mice are more susceptible to DNA-virus infection and death than their wild-type counterpart (PubMed:25299331).|||Interacts with STING1; ZDHHC1 constitutively interacts with STING1 and in presence of DNA viruses activates it by promoting its cGAMP-induced oligomerization and the recruitment of downstream signaling components.|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates (PubMed:23687301). Has a palmitoyltransferase activity toward NCDN and regulates NCDN association with endosome membranes through this palmitoylation (PubMed:23687301).|||The DHHC domain is required for palmitoyltransferase activity. http://togogenome.org/gene/10090:Fkrp ^@ http://purl.uniprot.org/uniprot/Q8CG64 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LicD transferase family.|||Catalyzes the transfer of CDP-ribitol to ribitol 5-phosphate previously attached by FKTN/fukutin of to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1) (PubMed:26923585). This constitutes the second step in the formation of the ribose 5-phosphate tandem repeat which links the phosphorylated O-mannosyl trisaccharide to the ligand binding moiety composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1 (PubMed:26923585).|||Cytoplasm|||Embryonic lethality before 12.5 dpc.|||Expressed in the retina, specifically in the inner segments of the photoreceptors, the outer plexiform layers, inner nuclear layers, and ganglion cell layers (at protein level) (PubMed:29416295). Expressed at highest levels in brain, lung, heart, kidney and liver (PubMed:12471058).|||Golgi apparatus membrane|||Homodimer; disulfide-linked (By similarity). Forms a complex composed of FKRP, FKTN/fukutin, and RXYLT1/TMEM5 (By similarity). Exists also as large multimeric protein complexes (By similarity). May interact with the dystrophin-glycoprotein complex (DGC) (PubMed:17452335).|||N-glycosylated.|||Rough endoplasmic reticulum|||Secreted|||sarcolemma http://togogenome.org/gene/10090:Rps6kl1 ^@ http://purl.uniprot.org/uniprot/Q8R2S1 ^@ Similarity ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. S6 kinase subfamily. http://togogenome.org/gene/10090:Serpinf2 ^@ http://purl.uniprot.org/uniprot/Q5ND36|||http://purl.uniprot.org/uniprot/Q61247 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the serpin family.|||Expressed by the liver and secreted in plasma.|||Forms protease inhibiting heterodimer with TMPRSS7.|||Proteolytically cleaved at Pro-35 by both the prolyl endopeptidase FAP form and antiplasmin-cleaving enzyme FAP soluble form to generate mature alpha-2-antiplasmin.|||Secreted|||Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin (By similarity). http://togogenome.org/gene/10090:Arhgdib ^@ http://purl.uniprot.org/uniprot/Q61599 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Rho GDI family.|||Interacts with RHOA. Interacts with RAC1. Interacts with RAC2. Interacts with CDC42.|||Preferentially expressed in hematopoietic cells.|||Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Regulates reorganization of the actin cytoskeleton mediated by Rho family members.|||cytosol http://togogenome.org/gene/10090:Esr2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Y6|||http://purl.uniprot.org/uniprot/A0A1W2P736|||http://purl.uniprot.org/uniprot/O08537 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA1, NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with UBE1C and AKAP13. Interacts with DNTTIP2 (By similarity). Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with DNAAF4. Interacts with PRMT2. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner (By similarity). Interacts with RBM39, in the presence of estradiol (E2) (PubMed:11704680).|||Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.|||Corresponds to exon 5 deletion (PubMed:9685228). May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.|||Corresponds to exon 6 deletion (PubMed:9685228). May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.|||Corresponds to exons 5 and 6 deletion.|||Expressed in prostate, ovary, Leydig cells and in epithelium of the efferent ductules and of the initial segment of the epididymis.|||Isoforms 1 and 2 are down-regulated by 17-beta-estradiol.|||Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner.|||Nucleus|||Phosphorylation at Ser-87 and Ser-105 recruits NCOA1. http://togogenome.org/gene/10090:Psmd9 ^@ http://purl.uniprot.org/uniprot/Q9CR00 ^@ Function|||Similarity|||Subunit ^@ Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex assembly is part of an intermediate PSMD9:PSMC6:PSMC3 module, also known as modulator trimer complex; PSMD9 is released during the further base assembly process (By similarity).|||Belongs to the proteasome subunit p27 family.|||Interacts with PSMC3. Part of a transient complex (modulator) containing PSMD9, PSMC6 and PSMC3 formed during the assembly of the 26S proteasome (By similarity). http://togogenome.org/gene/10090:Sgcz ^@ http://purl.uniprot.org/uniprot/Q8BX51 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sarcoglycan beta/delta/gamma/zeta family.|||Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix. May play a role in the maintenance of striated muscle membrane stability.|||Expressed in the heart, skeletal muscle and arterial vascular smooth muscle.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Khdc1c ^@ http://purl.uniprot.org/uniprot/Q4KL78 ^@ Similarity ^@ Belongs to the KHDC1 family. http://togogenome.org/gene/10090:Rdh13 ^@ http://purl.uniprot.org/uniprot/Q8CEE7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Mitochondrion inner membrane|||Retinol dehydrogenase with a clear preference for NADP. Oxidizes all-trans-retinol, but seems to reduce all-trans-retinal with much higher efficiency. Has no activity towards steroid. http://togogenome.org/gene/10090:Ribc2 ^@ http://purl.uniprot.org/uniprot/Q9D4Q1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RIB43A family.|||Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.|||cilium axoneme http://togogenome.org/gene/10090:Ube2w ^@ http://purl.uniprot.org/uniprot/Q8VDW4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Specifically monoubiquitinates the N-terminus of various substrates, including ATXN3, MAPT/TAU, POLR2H/RPB8 and STUB1/CHIP, by recognizing backbone atoms of disordered N-termini (PubMed:21855799, PubMed:21229326). Involved in degradation of misfolded chaperone substrates by mediating monoubiquitination of STUB1/CHIP, leading to recruitment of ATXN3 to monoubiquitinated STUB1/CHIP, and restriction of the length of ubiquitin chain attached to STUB1/CHIP substrates by ATXN3 (PubMed:21855799). After UV irradiation, but not after mitomycin-C (MMC) treatment, acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway (PubMed:21229326). In vitro catalyzes 'Lys-11'-linked polyubiquitination. UBE2W-catalyzed ubiquitination occurs also in the presence of inactive RING/U-box type E3s, i.e. lacking the active site cysteine residues to form thioester bonds with ubiquitin, or even in the absence of E3, albeit at a slower rate (By similarity).|||Autoubiquitinated at Met-1.|||Belongs to the ubiquitin-conjugating enzyme family.|||Homodimer (By similarity). Interacts with FANCL. Interacts with STUB1/CHIP.|||Nucleus http://togogenome.org/gene/10090:Ormdl3 ^@ http://purl.uniprot.org/uniprot/Q9CPZ6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORM family.|||Ceramide-sensitive subunit of the serine palmitoyltransferase (SPT) complex, which is also composed of SPTLC1, SPTLC2/3 and SPTSSA/B.|||Ceramides bind to ORMDL3 N-terminus and stabilize it in a conformation that physically restricts the accessibility of the substrates to their binding sites in the serine palmitoyltransferase (SPT) complex, hence inhibiting SPT catalytic activity. In the absence of ceramides, the N-terminus is flexible and permits substrate binding, thus liberating SPT from inhibition.|||Endoplasmic reticulum membrane|||No overt phenotype, although knockout mice show elevated brain levels of sphingolipids, including dihydrosphingosine, dihydroceramide, ceramide and sphingosine, compared with wild-type animals (PubMed:31880535). Double knockdown of ORMDL1 and ORMDL3 show elevated brain levels of sphingolipids, compared with single knockout and wild-type animals (PubMed:31880535). At 8 weeks of age, both male and female ORMDL1/3 double knockout mice weigh significantly less than wild-type mice and exhibit impaired myelination and motor-function abnormalities (PubMed:31880535). The triple knockout ORMDL1, ORMDL2 and ORMDL3 is not viable (PubMed:31880535).|||Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:31880535, PubMed:30700557). When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (By similarity).|||When hydroxylated at Pro-137, ubiquitinated via 'Lys-48'-linkage, leading to proteasomal degradation. In endothelial cells, ORMDL3 proteasomal degradation is controlled by the sphingosine 1-phosphate receptor signaling pathway. http://togogenome.org/gene/10090:0610009B22Rik ^@ http://purl.uniprot.org/uniprot/Q8R3W2|||http://purl.uniprot.org/uniprot/Q9CQP2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAPP small subunits family. Sedlin subfamily.|||Cytoplasm|||Endoplasmic reticulum-Golgi intermediate compartment|||Expressed in chondrocytes at various stages of differentiation, including proliferating, prehypertrophic and hypertrophic chondrocytes in the distal femoral joint.|||Nucleus|||Part of the multisubunit TRAPP (transport protein particle) complex. Interacts with ENO1, PITX1, SF1 and TRAPPC2L (By similarity). Interacts with TRAPPC3.|||Prevents ENO1-mediated transcriptional repression and antagonizes ENO1-mediated cell death. May play a role in vesicular transport from endoplasmic reticulum to Golgi (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Treh ^@ http://purl.uniprot.org/uniprot/E9PYP7|||http://purl.uniprot.org/uniprot/Q9JLT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 37 family.|||Cell membrane|||Homodimer; disulfide-linked.|||Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose. http://togogenome.org/gene/10090:Dlx2 ^@ http://purl.uniprot.org/uniprot/P40764|||http://purl.uniprot.org/uniprot/Q52KJ2 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator (PubMed:21875655). Activates transcription of CGA/alpha-GSU, via binding to the downstream activin regulatory element (DARE) in the gene promoter (PubMed:23371388). Plays a role in terminal differentiation of interneurons, such as amacrine and bipolar cells in the developing retina (PubMed:21875655). Likely to play a regulatory role in the development of the ventral forebrain (PubMed:1678612). May play a role in craniofacial patterning and morphogenesis (PubMed:1678612).|||Belongs to the distal-less homeobox family.|||Developmentally regulated (PubMed:1678612, PubMed:1687503). Initially expressed in the branchial arches at 8.5 dpc, expression is confined to the maxillary and mandibular portions of the branchial arches at 9.5 dpc (PubMed:7893603). Expressed in the caudal portion of the mandibular process and the forebrain at 10.5 dpc (PubMed:7893603). Expressed in developing retinal progenitor cells at 12 dpc (PubMed:21875655). Expressed in the auditory hillocks, ventral olfactory bulbs, the oral epithelium and the external naris at 12.5 dpc (PubMed:7893603). Expressed in the condensed mesenchyme from which the malleus and incus develop at 13.5 dpc (PubMed:7893603). Expressed in the developing otic vesicle at 11.5 dpc, expression is then restricted to the vestibular region at 12.5 and 13.5 dpc (PubMed:7893603). Expression declines thereafter with no expression detected in the developing inner ear at 14.5 dpc (PubMed:7893603). Expressed in the oral epithelium and adjacent mesenchyme at sites of tooth development at 12.5 dpc (PubMed:7893603). Found in the dental epithelium and the adjacent mesenchyme of both incisors and molars at 13.5 dpc, expression is restricted to the ectoderm-derived ameloblast layer at 16.5 dpc (PubMed:7893603). Expressed in a patchy pattern in the epithelium of the upper lip at 12.5 dpc, however expression is lost by 14.5 dpc (PubMed:7893603).|||Expressed only in neural and other ectodermal structures of the head: the brain, the vomeronasal organ, and the preameloblasts of the teeth (PubMed:8098616). Primarily expressed in the germinal cells of the ventral forebrain in the midgestational embryo, and in both dorsal and ventral ventricular zones in late embryogenesis and early postnatal life (PubMed:8098616). Expressed in the inner nuclear layer of the retina (PubMed:21875655).|||Interacts (via homeobox DNA-binding domain) with POU4F2; this interaction enhances retinal ganglion cell (RGC) differentiation (PubMed:21875655).|||Nucleus|||Phosphorylated by serine/threonine kinases. http://togogenome.org/gene/10090:Tpo ^@ http://purl.uniprot.org/uniprot/P35419 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxidase family. XPO subfamily.|||Binds 1 Ca(2+) ion per heterodimer.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.|||Cleaved in its N-terminal part.|||Heme is covalently bound through a H(2)O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface (By similarity).|||Interacts with DUOX1, DUOX2 and CYBA.|||Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).|||Membrane http://togogenome.org/gene/10090:Atf7ip2 ^@ http://purl.uniprot.org/uniprot/Q3UL97 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MCAF family.|||Expressed in early mouse embryo, especially in the embryonic gonad from 11.5 dpc. Continuously expressed from newborn testis to adult.|||Expressed in testis.|||Interacts with MBD1, SETDB1 and SP1. Probably forms a complex with SETDB1 and MBD1 (By similarity).|||Nucleus|||Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context. Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing SETDB1. The complex formed with MBD1 and SETDB1 represses transcription and probably couples DNA methylation and histone H3 'Lys-9' trimethylation (H3K9me3) activity (By similarity). http://togogenome.org/gene/10090:Cdc20 ^@ http://purl.uniprot.org/uniprot/Q9JJ66 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated. Deacetylated at Lys-66 by SIRT2; deacetylation enhances the interaction of CDC20 with CDC27, leading to activation of anaphase promoting complex/cyclosome (APC/C).|||Belongs to the WD repeat CDC20/Fizzy family.|||Component of a complex with CDC20, CDC27, SPATC1 and TUBG1 (PubMed:15280373). Interacts with NEUROD2 (PubMed:19900895). Interacts with dimeric MAD2L1 in its closed conformation form (By similarity). Interacts with BUB1B (By similarity). The phosphorylated form interacts with APC/C (By similarity). Interacts with NINL (By similarity). May interact with MAD2L2 (By similarity). Interacts with CDK5RAP2 (By similarity). Interacts with SIRT2 (PubMed:22014574). Interacts with isoform 1 of NEK2 (By similarity). Interacts with HSF1 (via phosphorylated form); this interaction occurs in mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated degradation of HSF1 by blocking the recruitment of the SCF(BTRC) ubiquitin ligase complex (By similarity). Interacts (via the N-terminal substrate-binding domain) with FBXO5 (PubMed:15526037). Interacts with CCNF (By similarity).|||Dephosphorylated by CTDP1.|||Involved in the metaphase/anaphase transition of cell cycle (PubMed:32666501). Required for full ubiquitin ligase activity of the anaphase promoting complex/cyclosome (APC/C) and may confer substrate specificity upon the complex. Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation. The CDC20-APC/C complex promotes proper dilation formation and radial migration by degrading CCDC41 (PubMed:34298015).|||Phosphorylated during mitosis (By similarity). Phosphorylated by BUB1 at Ser-41; Ser-72; Ser-92; Ser-153; Thr-157 and Ser-161 (By similarity). Phosphorylated by NEK2 (By similarity).|||Ubiquitinated and degraded by the proteasome during spindle assembly checkpoint. Ubiquitinated at Lys-490 during prometaphase. Ubiquitination at Lys-485 and Lys-490 has no effect on its ability to bind the APC/C complex (By similarity).|||centrosome|||kinetochore|||spindle pole http://togogenome.org/gene/10090:Cxcr6 ^@ http://purl.uniprot.org/uniprot/Q9EQ16 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for the C-X-C chemokine CXCL16. http://togogenome.org/gene/10090:Jakmip1 ^@ http://purl.uniprot.org/uniprot/Q8BVL9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with microtubules and may play a role in the microtubule-dependent transport of the GABA-B receptor. May play a role in JAK1 signaling and regulate microtubule cytoskeleton rearrangements.|||Belongs to the JAKMIP family.|||Homodimer (By similarity). Interacts with JAK1 and TYK2 (By similarity). Forms a complex with GABBR1 and KIF5B/kinesin-1.|||Membrane|||Phosphorylated.|||cytoskeleton http://togogenome.org/gene/10090:Ppm1d ^@ http://purl.uniprot.org/uniprot/Q3TZJ9|||http://purl.uniprot.org/uniprot/Q80WV2|||http://purl.uniprot.org/uniprot/Q9QZ67 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||By p53.|||Interacts with CHEK1 and CHEK2; dephosphorylates them. Interacts with MAPK14.|||Involved in the negative regulation of p53 expression. Required for the relief of p53-dependent checkpoint mediated cell cycle arrest. Binds to and dephosphorylates 'Ser-15' of TP53 and 'Ser-345' of CHEK1 which contributes to the functional inactivation of these proteins. Mediates MAPK14 dephosphorylation and inactivation (By similarity). Is also an important regulator of global heterochromatin silencing and critical in maintaining genome integrity (PubMed:24135283).|||Knockout mice show defective spermatogenesis. On histological sections, testes display an abnormal architecture and considerably narrower seminiferous tubules than those of wild-type mice, accompanied by changes in heterochromatin structure and globally altered gene expression in germ cells, and depletion of the most differentiated germ cell types.|||Nucleus|||Ubiquitously expressed.|||cytosol http://togogenome.org/gene/10090:Veph1 ^@ http://purl.uniprot.org/uniprot/A1A535 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MELT/VEPH family.|||Cell membrane|||Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling.|||Interacts with TGFBR1.|||No visible phenotype.|||Specifically expressed in kidney and eye. In the eye, expressed in retinal pigmented epithelium but not in the neural retina.|||Strongly expressed in brain and eye from 12 dpc to 17 dpc. After birth, brain expression decreases, whereas eye expression remains stable.|||The PH domain is required for membrane targeting. http://togogenome.org/gene/10090:Melk ^@ http://purl.uniprot.org/uniprot/Q61846 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by autophosphorylation of the T-loop at Thr-167 and Ser-171: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-167 is not mediated by STK11/LKB1 but via autophosphorylation instead. Inhibited by calcium-binding. Kinase activity is also regulated by reducing agents: dithiothreitol (DTT) or reduced glutathione are required for kinase activity in vitro; such dependence is however not due to the presence of disulfide bonds (By similarity).|||Autophosphorylated: autophosphorylation of the T-loop at Thr-167 and Ser-171 is required for activation.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cell membrane|||Expressed in testis, ovary, thymus, spleen and T-cell. Expressed by neural progenitors: highly enriched in cultures containing multipotent progenitors.|||Expressed in the 2-cell-stage embryo, followed by a strong expression at 8-cell-stage.|||Monomer. Interacts with ZNF622 and PPP1R8 (By similarity).|||Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis.|||The KA1 domain mediates binding to phospholipids and targeting to membranes. http://togogenome.org/gene/10090:Grik1 ^@ http://purl.uniprot.org/uniprot/Q3UZT1|||http://purl.uniprot.org/uniprot/Q8BQZ0|||http://purl.uniprot.org/uniprot/Q8BRT2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.|||Cell membrane|||Membrane|||Postsynaptic cell membrane|||Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. http://togogenome.org/gene/10090:Pthlh ^@ http://purl.uniprot.org/uniprot/Q540C1|||http://purl.uniprot.org/uniprot/Q924X4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the parathyroid hormone family.|||Cytoplasm|||Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Up-regulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath.|||Nucleus|||Osteostatin is a potent inhibitor of osteoclastic bone resorption.|||PTHrP interacts with PTH1R (via N-terminal extracellular domain).|||Secreted|||There are several secretory forms, including osteostatin, arising from endoproteolytic cleavage of the initial translation product. Each of these secretory forms is believed to have one or more of its own receptors that mediates the normal paracrine, autocrine and endocrine actions. http://togogenome.org/gene/10090:Fxyd1 ^@ http://purl.uniprot.org/uniprot/Q9Z239 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adults exhibit increased cardiac mass, larger cardiomyocytes, higher ejection fractions (the amount of blood pumped out of the ventricles with each contraction) and reduced sodium/potassium-transporting ATPase (NKA) activity in a mixed strain background of C57BL/6 and 129/SvJ (PubMed:15563542). Decreased cardiac contractile function and increased NKA activity in a congenic C57BL/6 background (PubMed:18065526). Increased glutathionylation of the NKA beta subunit ATP1B1 (PubMed:21454534). Decreased excitability of neurons which secrete gonadotropin-releasing hormone and delayed female puberty (PubMed:19187398).|||Apical cell membrane|||Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell (PubMed:15563542, PubMed:18065526). Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated (By similarity). Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1 (PubMed:21454534). Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone (PubMed:19187398).|||Belongs to the FXYD family.|||Homotetramer (By similarity). Monomer (By similarity). Regulatory subunit of the sodium/potassium-transporting ATPase (NKA) which is composed of a catalytic alpha subunit, a non-catalytic beta subunit and an additional regulatory subunit (By similarity). The monomeric form associates with NKA while the oligomeric form does not (PubMed:23532852). Interacts with the catalytic alpha-1 subunit ATP1A1 (PubMed:17283221). Also interacts with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3 (By similarity). Very little interaction with the catalytic alpha subunits ATP1A1, ATP1A2 or ATP1A3 when phosphorylated at Ser-83 (By similarity). Interacts with the non-catalytic beta-1 subunit ATP1B1 (By similarity). Oxidative stress decreases interaction with ATP1A1 but increases interaction with ATP1B1 (By similarity).|||Major plasma membrane substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in several different tissues. Phosphorylated in response to insulin and adrenergic stimulation. Phosphorylation at Ser-88 stimulates sodium/potassium-transporting ATPase activity while the unphosphorylated form inhibits sodium/potassium-transporting ATPase activity. Phosphorylation increases tetramerization, decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity. Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3. May be phosphorylated by DMPK.|||Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.|||T-tubule|||The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.|||caveola|||sarcolemma http://togogenome.org/gene/10090:Tmem192 ^@ http://purl.uniprot.org/uniprot/Q9CXT7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM192 family.|||Homodimer.|||Late endosome|||Lysosome membrane http://togogenome.org/gene/10090:Odad4 ^@ http://purl.uniprot.org/uniprot/Q9D4B2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ At 7.5 dpc, strong expression restricted to the ventral node, the left-right organizer (PubMed:27486780). Up-regulated in tracheal epithelial cells during in vitro differentiation into multiciliated cells (PubMed:25860617).|||Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Plays an essential role for the assembly of ODA-DC and for the docking of ODA in ciliary axoneme.|||Component of the outer dynein arm-docking complex along with ODAD1, ODAD2, and ODAD3 (By similarity). Interacts with ODAD1; this interaction may facilitate the recruitment and/or attachment of outer dynein arm docking complex proteins, including ODAD1, ODAD3 and ODAD2, to ciliary axonemes (By similarity). Interacts with components of the IFT complex A, including IFT140, TTC21B/IFT139 and WDR19/IFT144, and the IFT complex B, including IFT46, IFT52 and IFT57 (PubMed:25860617).|||Heterozygous intercrosses reveal deviation from the Mendelian distribution, with only 6 homozygous out of 53 born mice, suggesting increased death in utero. Most surviving homozygous mice present with small body size, some with hydrocephalus at the age of 2 weeks. They display a variety of left-right body asymmetry defects, including reversal of lung lobation or dextrocardia. At the cell level, the trachea and fallopian tubes of mutant animals show absence of outer dynein arms from the ciliary axonemes, and consequently severe reduction of cilia beating. There is no evidence of short cilia or a reduction in cilia number.|||cilium|||cilium axoneme http://togogenome.org/gene/10090:Wdr5b ^@ http://purl.uniprot.org/uniprot/Q9D7H2 ^@ Function|||Similarity|||Subunit ^@ Belongs to the WD repeat WDR5/wds family.|||May function as a substrate receptor for CUL4-DDB1 ubiquitin E3 ligase complex.|||Probable part of a cullin-RING E3 protein ligase complex containing CUL4B-DDB1 and a substrate-recruiting component (DCAF). Interacts with CUL4B and DDB1. http://togogenome.org/gene/10090:Ypel4 ^@ http://purl.uniprot.org/uniprot/Q0VEE5|||http://purl.uniprot.org/uniprot/Q65Z93 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the yippee family.|||Detected in brain, spleen and testis.|||nucleolus http://togogenome.org/gene/10090:Spata22 ^@ http://purl.uniprot.org/uniprot/Q5SV06 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of a multiprotein complex with MEIOB and RPA2 (PubMed:24240703). Interacts with the complex BRME1:HSF2BP:BRCA2 (PubMed:32345962).|||In testis, weakly present from 8 dpp, and readily detectable from 10 dpp, with expression sustained through adulthood. Present in all populations of spermatocytes (at protein level).|||Meiosis-specific protein required for homologous recombination in meiosis I.|||Mice develop and grow normally but show infertility in both sexes. Gametogenesis is affected with germ cells that do not progress beyond early meiotic prophase, with subsequent germ cell loss in both males and females.|||Specifically expressed in gonadal germ cells, when male and female germ cells progress through prophase of meiosis I. http://togogenome.org/gene/10090:Or2t48 ^@ http://purl.uniprot.org/uniprot/Q8VGD9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Morc4 ^@ http://purl.uniprot.org/uniprot/Q8BMD7 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation ^@ Contaminating sequence. Potential poly-A sequence.|||Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) 'Lys-4' on histone H3 (By similarity). The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0 (By similarity).|||Nucleus|||The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3. http://togogenome.org/gene/10090:Ankk1 ^@ http://purl.uniprot.org/uniprot/Q8BZ25 ^@ Similarity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Nat3 ^@ http://purl.uniprot.org/uniprot/P50296|||http://purl.uniprot.org/uniprot/Q546K5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the arylamine N-acetyltransferase family.|||Cytoplasm|||Participates in the detoxification of a plethora of hydrazine and arylamine drugs. http://togogenome.org/gene/10090:A2m ^@ http://purl.uniprot.org/uniprot/Q6GQT1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.|||Expressed in uterus of pregnant females during decidualization from 6 dpc with highest level around 10 dpc declining throughout the rest of the pregnancy.|||Expressed in uterus, mesometrial lymphoid aggregate and mammary tissue during pregnancy. Expressed in ovary, testis and kidney. Low level expression in heart. Not expressed in liver.|||Homotetramer; disulfide-linked.|||Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase (By similarity).|||Secreted http://togogenome.org/gene/10090:Matcap1 ^@ http://purl.uniprot.org/uniprot/Q810A5 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase MATCAP family.|||Binds 1 zinc ion per subunit.|||Metalloprotease with an atypical HExxxH zinc-binding motif instead of HExxH, which interrupts the active site-containing helix without affecting the integrity of the catalytic site arrangement.|||No visible phenotype: mice are viable and fertile and display no gross alterations (PubMed:35482892). Mice lacking both Matcap and Svbp are viable but show a reduction in brain volume: microcephaly is associated with proliferative defects during neurogenesis and abnormal behavior (PubMed:35482892). Cells lacking both Matcap and Svbp show abolished tubulin detyrosination (PubMed:35482892).|||The N-terminal disordered region enhances its anchoring on microtubules, while dampening processivity on the polymerized substrate.|||Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:35482892). Also able to remove the C-terminal phenylalanine residue of alpha-tubulin TUBA8. Recognizes adjacent tubulin dimers along the same protofilament (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Slc35f4 ^@ http://purl.uniprot.org/uniprot/B2RSS2|||http://purl.uniprot.org/uniprot/Q8BZK4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC35F solute transporter family.|||Membrane|||Putative solute transporter. http://togogenome.org/gene/10090:Thoc1 ^@ http://purl.uniprot.org/uniprot/Q8R3N6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An intact death domain is needed for apoptosis.|||Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Binds to the hypophosphorylated form of RB1. Interacts with THOC2, DDX39B and RNA polymerase II (By similarity). Interacts with THOC5 (PubMed:16909111). Interacts with LUZP4 (By similarity).|||Expression is altered specifically during apoptosis and is accompanied by the appearance of novel forms with smaller apparent molecular mass.|||In the inner ear, specifically expressed in inner and outer hair cells (at protein level).|||Mice show early embryonic lethality and severely diminished fertility.|||Nucleus|||Nucleus matrix|||Participates in an apoptotic pathway which is characterized by activation of caspase-6, increases in the expression of BAK1 and BCL2L1 and activation of NF-kappa-B. This pathway does not require p53/TP53, nor does the presence of p53/TP53 affect the efficiency of cell killing. Activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. Apoptosis is inhibited by association with RB1 (By similarity). Essential for early embryonic development. Required for normal gene expression during postnatal testis development.|||Polyubiquitinated, leading to proteasomal degradation; probably involves NEDD4.|||Required for efficient export of polyadenylated RNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. Regulates transcriptional elongation of a subset of genes. Involved in genome stability by preventing co-transcriptional R-loop formation (By similarity). May play a role in hair cell formation, hence may be involved in hearing (By similarity).|||Widely expressed during embryonic development.|||cytosol|||nucleoplasm http://togogenome.org/gene/10090:Hira ^@ http://purl.uniprot.org/uniprot/Q61666 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat HIR1 family.|||Embryonic stem cells (ES cells) exhibit accelerated differentiation in the early stages which may be attributable to increased availability of soluble histones.|||Expressed in cerebrum, cerebellum, heart, kidney, liver, lung and spleen.|||Interacts with CCNA1, HIRIP3 and NFU1/HIRIP5 (By similarity). Part of a complex which includes ASF1A, CABIN1, histone H3.3, histone H4 and UBN1 (By similarity). Interacts with histone H2B, histone H3-3B, PAX3 and PAX7 (PubMed:9731536).|||Nucleus|||PML body|||Phosphorylated by CDK2/CCNA1 and CDK2/CCNE1 on Thr-554 in vitro (By similarity). Also phosphorylated on Thr-554 in vivo.|||Required for the periodic repression of histone gene transcription during the cell cycle (By similarity). Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit.|||Sumoylated.|||Throughout development the long isoform is more abundant. In embryos, ubiquitously expressed with high levels detected in cranial neural folds, subregions of pharyngeal arches 1 and 2, circumpharyngeal neural crest and limb buds. http://togogenome.org/gene/10090:Isx ^@ http://purl.uniprot.org/uniprot/A1A546|||http://purl.uniprot.org/uniprot/B1Q2M1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Appears late in development, just before the villus transition in intestine morphogenesis. Restricted to the epithelial compartment in both adult and fetal intestine.|||Expressed in intestinal epithelial cells from the duodenum to the proximal colon.|||Mice appear healthy for at least 1 year and display normal histological features in the gut. They however show defects in intestinal gene expression with a dysregulation of the scavenger receptor Scarb1.|||Nucleus|||Transcription factor that regulates gene expression in intestine. May participate in vitamin A metabolism most likely by regulating BCO1 expression in the intestine. http://togogenome.org/gene/10090:Vmn1r189 ^@ http://purl.uniprot.org/uniprot/Q8K3N3 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Ctxn1 ^@ http://purl.uniprot.org/uniprot/Q8K129 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cortexin family.|||May mediate extracellular or intracellular signaling of cortical neurons during forebrain development.|||Membrane http://togogenome.org/gene/10090:Ms4a13 ^@ http://purl.uniprot.org/uniprot/Q5FWC3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the MS4A family.|||It is uncertain whether Met-1 or Met-22 is the initiator.|||May be involved in signal transduction as a component of a multimeric receptor complex.|||Membrane http://togogenome.org/gene/10090:Or5p76 ^@ http://purl.uniprot.org/uniprot/Q8VG09 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Krt85 ^@ http://purl.uniprot.org/uniprot/Q9Z2T6 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Med17 ^@ http://purl.uniprot.org/uniprot/Q8VCD5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 17 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with STAT2 (By similarity). Interacts with GATA1 and PPARG.|||Nucleus http://togogenome.org/gene/10090:Kat8 ^@ http://purl.uniprot.org/uniprot/Q9D1P2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoacetylation at Lys-274 is required for binding histone H4 with high affinity and for proper function.|||Belongs to the MYST (SAS/MOZ) family.|||Cerebrum-specific knockout of the gene resulted in impaired postnatal growth, hyperactive behavior, and early death. Analysis of mutant mice at various stages of embryonic development showed cerebral hypoplasia with defects in neocortical lamination, abnormal neuronal differentiation with decreased neuronal progenitor cells, and aberrant neuronal migration. These defects were associated with impaired cell proliferation, increased apoptosis, defective neurosphere formation in vitro, and decreased H4K16 propionylation and acetylation in the cerebrocortical neuroepithelium.|||Chromosome|||Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the MOF/KAT8, MSL1/hampin, MSL2L1 and MSL3L1 (By similarity). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (By similarity). Interacts with KANSL1; the interaction is direct (By similarity). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MOF/KAT8, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (By similarity). Interacts with the chromodomain of MORF4L1/MRG15 (By similarity). Interacts with ATM (via its Tudor-knot domain) (By similarity). Interacts with MSL1; the interaction is direct (PubMed:21217699, PubMed:17335777). Interacts with MSL3 (By similarity). Interacts with NELFD (PubMed:17335777).|||Histone acetyltransferase which may be involved in transcriptional activation (PubMed:31794431). May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac (Probable). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex. Can also acetylate TP53/p53 at 'Lys-120' (By similarity).|||Nucleus http://togogenome.org/gene/10090:Dkc1 ^@ http://purl.uniprot.org/uniprot/Q9ESX5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pseudouridine synthase TruB family.|||Cajal body|||Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:12522253, PubMed:15240872). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs (PubMed:12522253, PubMed:15240872). Required for ribosome biogenesis and telomere maintenance (By similarity). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (By similarity).|||Expressed throughout development, particularly in developing epithelial tissues.|||Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit. The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate. During assembly, the complex contains NAF1 instead of GAR1/NOLA1. The complex also interacts with TERC, which contains a 3'-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140. H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex. Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1. Interacts with SHQ1; this interaction may lead to the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA (By similarity). Interacts with HMBOX1 (By similarity). Interacts with DHX36 (By similarity).|||Ubiquitously expressed, with elevated levels in Purkinje cells, the olfactory bulb, and Leydig cells of the testis.|||nucleolus http://togogenome.org/gene/10090:Soat2 ^@ http://purl.uniprot.org/uniprot/O88908 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.|||Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. Utilizes oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-CoA) as substrates. May provide cholesteryl esters for lipoprotein secretion from hepatocytes and intestinal mucosa.|||Each protomer consists of 9 transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site: acyl-CoA enters the active site through the cytosolic tunnel, whereas cholesterol enters from the side through the transmembrane tunnel.|||Endoplasmic reticulum membrane|||May form homo- or heterodimers (By similarity). Interacts with INSIG1; the interaction is direct and promotes association with AMFR/gp78 (By similarity).|||Mice are more susceptible to high-fat diet-induced insulin resistance.|||Oxidized at Cys-280: high concentration of cholesterol and fatty acid induce reactive oxygen species, which oxidizes Cys-280, preventing ubiquitination at the same site, and resulting in protein stabilization.|||Polyubiquitinated by AMFR/gp78 at Cys-280, leading to its degradation when the lipid levels are low. Association with AMFR/gp78 is mediated via interaction with INSIG1. High concentration of cholesterol and fatty acid results in Cys-280 oxidation, preventing ubiquitination at the same site, resulting in protein stabilization. http://togogenome.org/gene/10090:Celf3 ^@ http://purl.uniprot.org/uniprot/Q8CIN6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CELF/BRUNOL family.|||Cytoplasm|||Nucleus|||RNA-binding protein involved in the regulation of pre-mRNA alternative splicing. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and developmentally regulated alternative splicing. Specifically activates exon 5 inclusion of cardiac isoforms of TNNT2 during heart remodeling at the juvenile to adult transition. Activates the splicing of MAPT/Tau exon 10. Binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the alternative exon 5 of TNNT2 pre-mRNA (By similarity). http://togogenome.org/gene/10090:Cyp21a1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J048|||http://purl.uniprot.org/uniprot/P03940|||http://purl.uniprot.org/uniprot/Q3UJ92 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane|||The leucine-rich hydrophobic amino acid N-terminal region probably helps to anchor the protein to the microsomal membrane. http://togogenome.org/gene/10090:Nabp1 ^@ http://purl.uniprot.org/uniprot/Q8BGW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SOSS-B family. SOSS-B2 subfamily.|||Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways (By similarity).|||Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1 (By similarity).|||Nucleus|||Ubiquitous with high expression in the thymus. http://togogenome.org/gene/10090:Usp13 ^@ http://purl.uniprot.org/uniprot/Q5BKP2 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Cytoplasm|||Deficient mice are more resistant than wild-type littermates to lethal HSV-1 infection. In addition, USP13 deficiency impairs autophagy in lungs of aged mice (PubMed:36150040).|||Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB. In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1. Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion. Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1.|||Interacts with UFD1. Interacts (via UBA domains) with SIAH2 (when ubiquitinated). Interacts with BAG6; the interaction is direct and may mediate UBL4A deubiquitination. Interacts (via UBA 2 domain) with AMFR; the interaction is direct. Interacts with UBL4A; may be indirect via BAG6. Interacts with NEDD4.|||Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes. The weak deubiquitinase activity in vitro suggests the existence of some mechanism that activates the enzyme (By similarity).|||The UBA domains mediate binding to ubiquitin.|||The UBP-type zinc finger has lost its ability to bind ubiquitin and USP13 is not activated by unanchored ubiquitin. http://togogenome.org/gene/10090:Arl6ip5 ^@ http://purl.uniprot.org/uniprot/Q8R5J9 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRA1 family.|||By methyl-beta-cyclodextrin. Up-regulated upon chronic morphine injection, in amygdala only, other brain regions remain unaffected. Induction by morphine may affect glutamate uptake in the amygdala, causing mice to develop morphine tolerance and dependence (PubMed:12438930). Was originally reported to be induced by retinoic acid (PubMed:12562531).|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in the cerebral cortex, cerebellum, hippocampus, olfactory bulbs, medulla oblongate and limbic system (at protein level) (PubMed:18684713). Ubiquitous.|||Homodimer. Heterodimer with ARL6IP1 (PubMed:18684713). Forms multimers. Interacts with ARL6 (PubMed:10508919). Interacts with prenylated RAB1A and RAB3A. Interacts with SLC1A1/EAAC1 (PubMed:18684713, PubMed:12119102). Interacts with RTN2 (via first transmembrane domain) (By similarity). Does not interact with VAMP1, VAMP2 or VAMP3 (By similarity).|||Regulates intracellular concentrations of taurine and glutamate (By similarity). Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner (PubMed:12119102, PubMed:18684713). Plays a role in the retention of SLC1A1/EAAC1 in the endoplasmic reticulum (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Usp20 ^@ http://purl.uniprot.org/uniprot/Q8C6M1 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family. USP20/USP33 subfamily.|||Cytoplasm|||Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis. Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination. Promotes cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'-linked ubiquitination of STING1 leading to its stabilization. Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1. Acts as a positive regulator for NF-kappa-B activation by TNF-alpha through deubiquitinating 'Lys-48'-linked polyubiquitination of SQSTM1, leading to its increased stability. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity. Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability. Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol.|||Endoplasmic reticulum|||Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with CCP110. Interacts with DIO2. Interacts with HIF1A. Interacts with ADRB2. Interacts with USP18.|||The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 55 is replaced by a Glu residue (By similarity).|||USP20-deletion mice produce decreased type I IFNs and proinflammatory cytokines and exhibit increased susceptibility to lethal viral infection compared with WT mice.|||Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.|||centrosome|||perinuclear region http://togogenome.org/gene/10090:Hsd17b1 ^@ http://purl.uniprot.org/uniprot/P51656|||http://purl.uniprot.org/uniprot/Q790P4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Cytoplasm|||Favors the reduction of estrogens and androgens. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2) (PubMed:9658408). Also has 20-alpha-HSD activity. Uses preferentially NADH (By similarity).|||Homodimer. Exists predominantly as an homodimer but also exits as monomer. http://togogenome.org/gene/10090:Ramacl ^@ http://purl.uniprot.org/uniprot/Q3TQP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the RAM family.|||Nucleus http://togogenome.org/gene/10090:Ogt ^@ http://purl.uniprot.org/uniprot/Q8CGY8 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.|||Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc) (PubMed:29465778). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, ATG4B, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU, NOD2 and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing. Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (By similarity).Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues. O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (By similarity). Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:23337503, PubMed:23395176). O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (By similarity). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Glycosylates HOXA1 (PubMed:29465778). O-glycosylates FNIP1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B (By similarity).|||Cell membrane|||Cell projection|||Cytoplasm|||Expression in the liver oscillates in a circadian manner.|||Homotrimer, oligomerizes via TPR repeats 6 and 7. Trimerization is not necessary for activity in vitro, however it increases affinity for UDP-GlcNAc (By similarity). Component of a THAP1/THAP3-HCFC1-OGT complex. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts directly with HCFC1; the interaction O-glycosylates HCFC1, regulates its proteolytic processing and transcriptional activity and, in turn, stabilizes OGT in the nucleus. Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase (By similarity). Interacts (via TPR 5-6) with TET1, TET2 and TET3 (PubMed:23352454). Interacts (via TPR repeats 6 and 7) with ATXN10 (PubMed:16182253). Interacts with histone H2B (By similarity). Interacts with BMAL1 (PubMed:23337503). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (PubMed:28554894). Interacts with SINHCAF (PubMed:28554894). Component of a complex composed of KMT2E/MLL5, OGT and USP7; the complex stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination and proteasomal-mediated degradation. Interacts (via TRP repeats) with KMT2E/MLL5 (via N-terminus). Interacts with USP7 (By similarity). Interacts with TRAK1; this interaction is not required for glycosylation of TRAK1 by this protein. Found in a complex with KIF5B, RHOT1, RHOT2 and TRAK1 (By similarity). Interacts (via TPR repeats domain) with HOXA1; the interaction takes place mainly in the nucleus (PubMed:29465778). Interacts with NSD2 (PubMed:19483677). Interacts with PROSER1; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2 (By similarity).|||Mitochondrion membrane|||Nucleus|||Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity.|||The TPR repeat domain is required for substrate binding and oligomerization.|||Ubiquitinated, leading to its proteasomal degradation. http://togogenome.org/gene/10090:Or2l13 ^@ http://purl.uniprot.org/uniprot/Q8VGX2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Acadvl ^@ http://purl.uniprot.org/uniprot/P50544 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acyl-CoA dehydrogenase family.|||Homodimer. Homodimerizes after import into the mitochondrion.|||Mitochondrion inner membrane|||S-nitrosylation at Cys-238 in liver improves catalytic efficiency.|||Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process breaking down fatty acids into acetyl-CoA and allowing the production of energy from fats. The first step of fatty acid beta-oxidation consists in the removal of one hydrogen from C-2 and C-3 of the straight-chain fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA. Among the different mitochondrial acyl-CoA dehydrogenases, very long-chain specific acyl-CoA dehydrogenase acts specifically on acyl-CoAs with saturated 12 to 24 carbons long primary chains. http://togogenome.org/gene/10090:Lrch4 ^@ http://purl.uniprot.org/uniprot/Q921G6 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Accessory protein that regulates signaling by multiple TLRs, acting as a broad-spanning regulator of the innate immune response. In macrophages, binds LPS and promotes proper docking of LPS in lipid raft membrane. May be required for lipid raft maintenance.|||Cell membrane|||Expression is inhibited by LPS.|||Widely expressed across tissues, with the most abundant expression in spleen, testes, thymus, intestine, and blood (PubMed:30523158). Expressed in macrophages (PubMed:30523158). http://togogenome.org/gene/10090:Rfc5 ^@ http://purl.uniprot.org/uniprot/Q5HZI8|||http://purl.uniprot.org/uniprot/Q9D0F6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the activator 1 small subunits family.|||Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA (By similarity).|||Nucleus|||The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. http://togogenome.org/gene/10090:Prkd3 ^@ http://purl.uniprot.org/uniprot/D3Z6I0|||http://purl.uniprot.org/uniprot/Q5FWX6|||http://purl.uniprot.org/uniprot/Q8K1Y2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by DAG and phorbol esters.|||Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains 1 and 2 bind both DAG and phorbol ester with high affinity and mediate translocation to the cell membrane. Autophosphorylation of Ser-734 and phosphorylation of Ser-730 by PKC relieves auto-inhibition by the PH domain.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.|||Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress (By similarity).|||Cytoplasm|||Membrane http://togogenome.org/gene/10090:Isy1 ^@ http://purl.uniprot.org/uniprot/Q69ZQ2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ISY1 family.|||Component of the spliceosome C complex required for the selective processing of microRNAs (miRNAs) during embryonic stem cell differentiation (PubMed:26255770, PubMed:29804889). Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (PubMed:26255770). Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (PubMed:29804889). Required during the transition of embryonic stem cells (ESCs) from the naive to primed state (PubMed:29804889). By enhancing miRNA biogenesis, promotes exit of ESCs from the naive state to an intermediate state of poised pluripotency, which precedes the transition to the primed state (PubMed:29804889). Involved in pre-mRNA splicing as component of the spliceosome.|||During embryoid body (EB) formation, expression peaks at day 1 of EB differentiation (at protein level) (PubMed:29804889). Expressed during embryonic stem cell differentiation in vitro, with high expression during the earliest time point of differentiation during a 'poised' pluripotency phase that occurs in between embryonic day 4.5 and embryonic day 5.5 (PubMed:26255770, PubMed:29804889).|||Identified in the spliceosome C complex. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex. The IB complex does not contain PRPF19. Interacts with CPSF3; this interaction is in an RNA independent manner (PubMed:26255770). Interacts with the microprocessor complex subunits DGCR8 and DROSHA; this interaction is in an RNA dependent manner (PubMed:26255770).|||Nucleus http://togogenome.org/gene/10090:Slc16a10 ^@ http://purl.uniprot.org/uniprot/Q3U9N9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Deficient mice grow and reproduce normally, show no gross phenotype and no obvious neurological defect. Deficient mice, however, display increased plasma, muscle and kidney aromatic amino acids (AAA) concentration under both normal and high protein diet, although this concentration remains normal in the liver, but it does not alter thyroid hormones homeostasis.|||Highly expressed in small intestine, particularly in jejunum and ileum, scarcely in colon and substantially in kidney, liver and skeletal muscle (PubMed:16245314). In the brain expression is low and appears to be restricted to a subset of neurons, microglia cells, and oligodendrocytes (PubMed:24994998).|||Not N-glycosylated.|||Sodium- and proton-independent thyroid hormones and aromatic acids transporter. Mediates both uptake and efflux of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) with high affinity, suggesting a role in the homeostasis of thyroid hormone levels (By similarity). Responsible for low affinity bidirectional transport of the aromatic amino acids, such as phenylalanine, tyrosine, tryptophan and L-3,4-dihydroxyphenylalanine (L-dopa) (PubMed:16245314). Plays an important role in homeostasis of aromatic amino acids (PubMed:23045339). http://togogenome.org/gene/10090:Mfsd14a ^@ http://purl.uniprot.org/uniprot/P70187 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily.|||Evenly distributed throughout the neonatal brain.|||Expressed in various tissues.|||Membrane http://togogenome.org/gene/10090:Zfyve1 ^@ http://purl.uniprot.org/uniprot/Q810J8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Endoplasmic reticulum|||Golgi apparatus|||Golgi stack|||Interacts with RAB18 (in GTP-bound form) (By similarity). Interacts with BSCL2 in a RAB18-dependent manner (By similarity). Interacts with ZW10 (By similarity).|||Lipid droplet|||Mitochondrion|||Plays a role in the formation of lipid droplets (LDs) which are storage organelles at the center of lipid and energy homeostasis (PubMed:30970241). Regulates the morphology, size and distribution of LDs (PubMed:31293035, PubMed:30970241). Mediates the formation of endoplasmic reticulum-lipid droplets (ER-LD) contact sites by forming a complex with RAB18 and ZW10 (By similarity). Binds to phosphatidylinositol 3-phosphate (PtdIns3P) through FYVE-type zinc finger (By similarity).|||Preautophagosomal structure|||Ubiquitous. http://togogenome.org/gene/10090:Upb1 ^@ http://purl.uniprot.org/uniprot/Q8VC97 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the carbon-nitrogen hydrolase superfamily. BUP family.|||Catalyzes a late step in pyrimidine degradation. Converts N-carbamoyl-beta-alanine (3-ureidopropanoate) into beta-alanine, ammonia and carbon dioxide. Likewise, converts N-carbamoyl-beta-aminoisobutyrate (3-ureidoisobutyrate) into beta-aminoisobutyrate, ammonia and carbon dioxide.|||Cytoplasm|||Homodimer, homotetramer, homooctamer; can also form higher homooligomers. http://togogenome.org/gene/10090:Dr1 ^@ http://purl.uniprot.org/uniprot/Q91WV0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NC2 beta/DR1 family.|||Heterodimer with DRAP1. DR1 exists in solution as a homotetramer that dissociates during interaction with TBP and then, after complexing with TBP, reassociates at a slow rate, to reconstitute the tetramer. Interacts with NFIL3. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1 (By similarity).|||Nucleus|||Phosphorylation regulates its interaction with TBP. Not phosphorylated when bound to DRAP1 (By similarity).|||The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (By similarity). http://togogenome.org/gene/10090:Slc24a2 ^@ http://purl.uniprot.org/uniprot/Q8BUN9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.|||Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+) (By similarity). Required for learming and memory by regulating neuronal Ca(2+), which is essential for the development of synaptic plasticity (PubMed:16407245).|||Cell membrane|||Mice display a significant reduction in Ca(2+) flux in cortical neurons, leading to a profound loss of long term potentiation and an increase in long term depression at hippocampal Schaffer/CA1 synapses, and clear deficits in specific tests of motor learning and spatial working memory (PubMed:16407245). Mice do not show any obvious loss of photoreceptor function in cones (PubMed:16407245). http://togogenome.org/gene/10090:Dop1a ^@ http://purl.uniprot.org/uniprot/H7BWZ9 ^@ Similarity ^@ Belongs to the dopey family. http://togogenome.org/gene/10090:Or5o1 ^@ http://purl.uniprot.org/uniprot/Q7TQW4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpr88 ^@ http://purl.uniprot.org/uniprot/B2RXU4|||http://purl.uniprot.org/uniprot/Q9EPB7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasm|||Expressed predominantly in the striatum.|||Membrane|||Mice have increased locomotion, increased motor stereotypical behavior, and impaired motor skill learning. Mutant mice also show facilitated hippocampal-mediated behaviors and decreased anxiety. Chronic blockade of delta opioid receptors and mu opioid, but not other Gi/o coupled receptors, using delta opioid receptor antagonist partially improved motor coordination and normalized spatial navigation and anxiety of mutant mice.|||Nucleus|||Probable G-protein coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function. http://togogenome.org/gene/10090:Rs1 ^@ http://purl.uniprot.org/uniprot/Q9Z1L4 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds negatively charged membrane lipids, such as phosphatidylserine and phosphoinositides (PubMed:17325137, PubMed:20677810). May play a role in cell-cell adhesion processes in the retina, via homomeric interaction between octamers present on the surface of two neighboring cells (By similarity). Required for normal structure and function of the retina (PubMed:11983912, PubMed:17325137).|||Cell membrane|||Detected in the eye cup (PubMed:11983912). Detected in retina, in the inner segment of the photoreceptors, the inner nuclear layer, the inner plexiform layer and the ganglion cell layer (at protein level) (PubMed:10915776, PubMed:11983912, PubMed:17325137). Restricted to the retina (PubMed:10023077, PubMed:10915776). At the mRNA level, detected only within the photoreceptor cell layer, most prominently within the inner segments of the photoreceptors (PubMed:10023077, PubMed:10915776). Undetectable in the inner plexiform layers and the inner nuclear layer (PubMed:10915776).|||Homooctamer of 4 homodimers; disulfide-linked. The homooctamer has a flat, cogwheel structure with a diameter of about 14 nm. Two stacked octamers can assemble to form a hexadecamer.|||No visible phenotype at birth (PubMed:11983912). After two months, mutant males display a profound disorganization of the inner and outer nuclear layer of the retina, with increased extracellular spaces in the region of photoreceptor ribbon synapses and the appearance of gaps, and a decrease in the number of photoreceptor cell outer segments (PubMed:11983912, PubMed:17325137). The number of cone photoreceptors is reduced threefold (PubMed:11983912). After three months, mutant males display a layer of small, cyst-like structures in the inner retina (PubMed:11983912). They have profoundly altered electroretinograms, indicating a decreased light sensitivity due to a decrease in the number of functional photoreceptors (PubMed:11983912).|||Secreted http://togogenome.org/gene/10090:Tnni1 ^@ http://purl.uniprot.org/uniprot/Q9WUZ5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the troponin I family.|||Binds to actin and tropomyosin.|||Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. http://togogenome.org/gene/10090:Wee1 ^@ http://purl.uniprot.org/uniprot/P47810 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.|||Binds 2 magnesium ions per subunit.|||Binds to 14-3-3 protein zeta.|||Dephosphorylated at Thr-239 by CTDP1 (By similarity). Dephosphorylated at Ser-52 and Ser-123 by the serine/threonine-protein phosphatase 2A preventing its ubiquitin-mediated degradation (By similarity).|||Nucleus|||Phosphorylated during M and G1 phases. Also autophosphorylated. Phosphorylation at Ser-642 by BRSK1 and BRSK2 in post-mitotic neurons, leads to down-regulate WEE1 activity in polarized neurons. Phosphorylated at Ser-52 and Ser-123 by PLK1 and CDK1, respectively, generating an signal for degradation that can be recognized by the SCF(BTRC) complex, leading to its ubiquitination and degradation at the onset of G2/M phase (By similarity).|||Synthesis is increased during S and G2 phases, presumably by an increase in transcription; activity is decreased by phosphorylation during m phase. Protein levels fall in M phase as a result of decreased synthesis combined with degradation. Activity seems to be negatively regulated by phosphorylation upon entry into mitosis, although N-terminal phosphorylation might also regulate the protein stability via protection from proteolysis or might regulate the subcellular location (By similarity).|||Ubiquitinated and degraded at the onset of G2/M phase. http://togogenome.org/gene/10090:Gm5127 ^@ http://purl.uniprot.org/uniprot/Q3UQH6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Spata31d1a ^@ http://purl.uniprot.org/uniprot/E9QA35|||http://purl.uniprot.org/uniprot/Q8CDS1|||http://purl.uniprot.org/uniprot/Q9CVY6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Cdon ^@ http://purl.uniprot.org/uniprot/Q32MD9 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells. Required for response to NTN3 and activation of NFATC3.|||Highly expressed in somites and the dorsal lips of the neural tube during embryogenesis. Detected at very low levels in adult tissues.|||N-glycosylated.|||Part of a complex that contains BOC, CDON, NEO1, cadherins and CTNNB1. Interacts with NTN3. Interacts with DHH, IHH and SHH (By similarity).|||Transiently up-regulated during myoblast differentiation. http://togogenome.org/gene/10090:Sdc2 ^@ http://purl.uniprot.org/uniprot/P43407 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the syndecan proteoglycan family.|||Cell surface proteoglycan which regulates dendritic arbor morphogenesis.|||Interacts (via cytoplasmic domain) with SARM1 (PubMed:21555464). Forms a complex with SDCBP and PDCD6IP (By similarity).|||Membrane|||O-glycosylated; contains both heparan sulfate and chondroitin sulfate.|||Phosphorylated on serine residues.|||Preferential expression in cells of mesenchymal origin. http://togogenome.org/gene/10090:Parp8 ^@ http://purl.uniprot.org/uniprot/F8WIK2|||http://purl.uniprot.org/uniprot/Q3UD82 ^@ Function|||PTM|||Similarity ^@ Auto-mono-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. http://togogenome.org/gene/10090:Ppp2r5c ^@ http://purl.uniprot.org/uniprot/Q60996|||http://purl.uniprot.org/uniprot/Q6ZQK4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphatase 2A regulatory subunit B56 family.|||Highest levels in heart, liver and brain. Lower levels in skeletal muscle, spleen, kidney and lung. Isoform 4 is testis-specific.|||Nucleus|||PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1 (By similarity). Interacts with SGO1; the interaction is direct. May interact with TP53 (By similarity). Interacts with IER3 and/or ERK kinases; regulates ERK dephosphorylation (By similarity). Interacts with CIP2A; this interaction stabilizes CIP2A (By similarity).|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation (By similarity).|||centromere http://togogenome.org/gene/10090:Dhtkd1 ^@ http://purl.uniprot.org/uniprot/A2ATU0 ^@ Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 2-oxoadipate dehydrogenase (E1a) component of the 2-oxoadipate dehydrogenase complex (OADHC). Participates in the first step, rate limiting for the overall conversion of 2-oxoadipate (alpha-ketoadipate) to glutaryl-CoA and CO(2) catalyzed by the whole OADHC. Catalyzes the irreversible decarboxylation of 2-oxoadipate via the thiamine diphosphate (ThDP) cofactor and subsequent transfer of the decarboxylated acyl intermediate on an oxidized dihydrolipoyl group that is covalently amidated to the E2 enzyme (dihydrolipoyllysine-residue succinyltransferase or DLST). Can catalyze the decarboxylation of 2-oxoglutarate in vitro, but at a much lower rate than 2-oxoadipate. Responsible for the last step of L-lysine, L-hydroxylysine and L-tryptophan catabolism with the common product being 2-oxoadipate.|||Belongs to the alpha-ketoglutarate dehydrogenase family.|||Intron retention.|||Mitochondrion|||The 2-oxoadipate dehydrogenase complex is composed of OADH (2-oxoadipate dehydrogenase; E1a), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). E1a functional unit is a dimer.|||The mitochondrial 2-oxoglutarate and 2-oxoadipate dehydrogenase complexes (OGDHC and OADHC, respectively) share their E2 (DLST) and E3 (dihydrolipoyl dehydrogenase or DLD) components, but the E1 component is specific to each complex (E1o and E1a, respectively). http://togogenome.org/gene/10090:Fndc5 ^@ http://purl.uniprot.org/uniprot/Q8K4Z2 ^@ Developmental Stage|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||During embryonic development, it is detected almost exclusively in the skeletal muscle, and at lower level in brain. In skeletal muscle, it is induced after myoblast differentiation, when myotube formation is promoted.|||In adult, it is highly expressed in skeletal muscle, heart and brain.|||Mediates beneficial effects of muscular exercise. Induces browning of white adipose tissue by stimulating UCP1 expression, at least in part, via the nuclear receptor PPARA.|||N-Glycosylated.|||Peroxisome membrane|||Secreted|||The extracellular domain is cleaved and released from the cell membrane.|||Up-regulated by muscular exercise. This effect can be mediated, at least partly, by PPARGC1A. http://togogenome.org/gene/10090:Trpv3 ^@ http://purl.uniprot.org/uniprot/Q8K424 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV3 sub-subfamily.|||Expressed in keratinocytes and hair follicles.|||May form a heteromeric channel with TRPV1. Interacts with TRPV1 (By similarity).|||Membrane|||Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen) (By similarity). http://togogenome.org/gene/10090:Gjb6 ^@ http://purl.uniprot.org/uniprot/P70689|||http://purl.uniprot.org/uniprot/Q3URC5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||A connexon is composed of a hexamer of connexins. Interacts with CNST.|||Belongs to the connexin family.|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Highly expressed in adult brain and skin. Less in uterus, lung and eye. Very low in testis and sciatic nerve. No expression before birth.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Tppp ^@ http://purl.uniprot.org/uniprot/Q3URG1|||http://purl.uniprot.org/uniprot/Q7TQD2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TPPP family.|||Degraded by the proteasome; zinc-binding inhibits degradation by the proteasome.|||Golgi outpost|||Homodimer. Binds tubulin; binding is inhibited by GTP (By similarity). Interacts with MAPK1. Interacts with GAPDH; the interaction is direct (By similarity). Interacts with LIMK1 (via the PDZ domain); the interaction is direct. Interacts with LIMK2. Interacts with HDAC6; thereby inhibiting the tubulin deacetylase activity of HDAC6. Interacts with aggregated SNCA; may have a pro-aggregatory role in synucleinopathies. Interacts with DYNLL1 (By similarity).Interacts (via C-terminus) with S100A2, S100A6 and S100B; these interactions inhibit TPPP dimerization (By similarity).|||Mice display hypomyelination with shorter, thinner myelin sheaths and show breeding and motor coordination deficits (PubMed:31522887). Oligodendrocytes have thinner and more numerous branches in proximal processes (PubMed:31522887). Fewer microtubules are nucleated from Golgi outposts and these are no longer arranged in parallel bundles with their growing plus-ends distal, but show random polarity (PubMed:31522887).|||Most of the protein is composed of disordered regions. Zinc-binding induces structural rearrangement by promoting molten globule state formation.|||Nucleus|||Phosphorylated by LIMK1 on serine residues; phosphorylation may alter the tubulin polymerization activity. Phosphorylation by LIMK2, but not LIMK1, regulates astral microtubule organization at early stage of mitosis. Phosphorylation by ROCK1 at Ser-31, Ser-106 and Ser-158 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin, increased cell motility and entry into S-phase. Phosphorylation by CDK1 inhibits the microtubule polymerizing activity.|||Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath (PubMed:31522887). Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath (PubMed:31522887). Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes (PubMed:31522887). Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear (By similarity). In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network (PubMed:18028908). Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6 (By similarity). Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility (By similarity). Plays a role in cell proliferation by regulating the G1/S-phase transition (By similarity). Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2 (By similarity).|||Widely expressed with higher expression in brain (at protein level).|||cytoskeleton|||microtubule organizing center|||spindle http://togogenome.org/gene/10090:Tollip ^@ http://purl.uniprot.org/uniprot/F7AT44|||http://purl.uniprot.org/uniprot/Q9QZ06 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tollip family.|||Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.|||Component of the signaling pathway of IL-1 and Toll-like receptors (By similarity). Inhibits cell activation by microbial products (By similarity). Recruits IRAK1 to the IL-1 receptor complex (By similarity). Inhibits IRAK1 phosphorylation and kinase activity. Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates (By similarity). The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (By similarity). In a complex with TOM1, recruits ubiquitin-conjugated proteins onto early endosomes (By similarity). Binds to phosphatidylinositol 3-phosphate (PtdIns(3)P) (By similarity).|||Cytoplasm|||Detected in heart, brain, spleen, lung, liver, skeletal muscle, kidney, thymus, pancreas and testis.|||Early endosome|||Endosome|||Oligomerizes. Binds to TLR2 and the TLR4-MD2 complex via its C-terminus. Exists as complex with IRAK1 in unstimulated cells. Upon IL-1 signaling, Tollip binds to the activated IL-1 receptor complex containing IL-1RI, IL-1RacP and the adapter protein MyD88, where it interacts with the TIR domain of IL-1RacP. MyD88 then triggers IRAK1 autophosphorylation, which in turn leads to the dissociation of IRAK1 from Tollip and IL-1RAcP. Found in a complex with TOM1; interacts (via N-terminus) with TOM1 (via GAT domain); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns(3)P (By similarity). Interacts with TOM1L2 (By similarity). Interacts with ATG8 family proteins (via the AIM motifs), and ubiquitin (via the CUE domain) (By similarity). Interacts with LRBA (By similarity).|||The N-terminal TOM1-binding domain (residues 1-53) is a disordered domain that partially folds when bound to the GAT domain of TOM1. http://togogenome.org/gene/10090:Oas3 ^@ http://purl.uniprot.org/uniprot/Q8VI93 ^@ Activity Regulation|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 2-5A synthase family.|||By type I interferon (IFN) and viruses.|||Cytoplasm|||Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L.|||Intestine.|||Monomer.|||Nucleus|||OAS domain 3 is catalytically active. OAS domain 1 has no catalytic activity but is essential for recognition of long dsRNAs.|||Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. Strongly activated by long dsRNAs at least 50 nucleotides in length. ssRNA does not activate the enzyme. http://togogenome.org/gene/10090:Ranbp17 ^@ http://purl.uniprot.org/uniprot/Q99NF8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the exportin family.|||Binds to nucleoporins and the GTP-bound form of Ran.|||Cytoplasm|||Highly expressed in primary spermatocytes and very weakly in pancreas.|||May function as a nuclear transport receptor.|||Nucleus|||nuclear pore complex http://togogenome.org/gene/10090:Vmn1r121 ^@ http://purl.uniprot.org/uniprot/K7N6J4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Vmn1r250 ^@ http://purl.uniprot.org/uniprot/K7N6B8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gulp1 ^@ http://purl.uniprot.org/uniprot/Q8K2A1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ced-6 family.|||Cytoplasm|||Detected throughout the brain, particularly in Purkinje cells, hippocampal and cortical neurons (at protein level).|||Homodimer. Interacts with clathrin and MEGF10 (By similarity). Interacts with GDP-bound ARF6, but not with GTP-bound ARF6. Part of a complex composed of GULP1, ACAP1 and ARF6. Interacts with ACAP1, LRP1 and STAB2.|||Modulates cellular glycosphingolipid and cholesterol transport. May play a role in the internalization of various LRP1 ligands, such as PSAP (By similarity). May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. Increases cellular levels of GTP-bound ARF6. http://togogenome.org/gene/10090:Cdk5rap1 ^@ http://purl.uniprot.org/uniprot/Q8BTW8 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methylthiotransferase family. MiaB subfamily.|||Binds 2 [4Fe-4S] clusters. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||Expressed in brain, liver, skeletal muscle and heart.|||Interacts with CDK5R1 (p35 form). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. Probably forms a complex with CDK5R1 and CDK5.|||Knockout mice show a deficiency in ms(2)i(6)A modification, resulting in impaired mitochondrial protein synthesis, which leads to respiratory defects.|||Methylthiotransferase that catalyzes the conversion of N6-(dimethylallyl)adenosine (i(6)A) to 2-methylthio-N6-(dimethylallyl)adenosine (ms(2)i(6)A) at position 37 (adjacent to the 3'-end of the anticodon) of four mitochondrial DNA-encoded tRNAs (Ser(UCN), Phe, Tyr and Trp) (PubMed:25738458). Essential for efficient and highly accurate protein translation by the ribosome (PubMed:25738458). Specifically inhibits CDK5 activation by CDK5R1 (By similarity). Essential for efficient mitochondrial protein synthesis and respiratory chain (PubMed:25738458).|||Mitochondrion http://togogenome.org/gene/10090:Bmp2k ^@ http://purl.uniprot.org/uniprot/Q91Z96 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Expressed in osteocytes and osteoblasts.|||May be involved in osteoblast differentiation.|||Nucleus http://togogenome.org/gene/10090:Pigz ^@ http://purl.uniprot.org/uniprot/Q8BTP0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 22 family. PIGZ subfamily.|||Endoplasmic reticulum membrane|||Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers a fourth mannose to some trimannosyl-GPIs during GPI precursor assembly. The presence of a fourth mannose in GPI is facultative and only scarcely detected, suggesting that it only exists in some tissues (By similarity). http://togogenome.org/gene/10090:Wac ^@ http://purl.uniprot.org/uniprot/Q924H7 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription. Regulates the cell-cycle checkpoint activation in response to DNA damage. Positive regulator of amino acid starvation-induced autophagy. Also acts as a negative regulator of basal autophagy. Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation. May negatively regulate the ubiquitin proteasome pathway.|||Interacts (via coiled coil domain) with RNF20, RNF40 and UBE2A. Interacts (via WW domain) with RNA polymerase II. Interacts with MTOR and other components of the MTOR pathway including RPTOR, RUVBL1, RUVBL2, TTI1 and TTI2.|||Nucleus|||Nucleus speckle|||Phosphorylated on tyrosine residues. http://togogenome.org/gene/10090:Crygn ^@ http://purl.uniprot.org/uniprot/Q8VHL5 ^@ Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens (Probable). Also plays an important role for integrity and function of auditory nuclei (PubMed:27517863).|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||Monomer.|||Primordially eye-specific. Present in lens nucleus. In the retina, expression in observed in the outer plexiform layer (containing photoreceptors axons and synapses) and photoreceptor outer segments (at protein level) (PubMed:15853812). Also detected in the auditory hindbrain where it is highly expressed in the medial nucleus of the trapezoid body, but also present in other nuclei of the superior olivary complex (PubMed:27517863). http://togogenome.org/gene/10090:Syap1 ^@ http://purl.uniprot.org/uniprot/Q9D5V6 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the liver, kidney, skeletal muscle and in white and brown adipose tissues (PubMed:23300339, PubMed:27344443). Expressed in the cortex, cerebellum, thalamus, hippocampus, braistem, olfactory bulb, spinal cord and striatum of the brain (PubMed:27344443). Expressed in most neuropil regions containing glutamatergic synaptic terminals (PubMed:27344443). Expressed in the CA1, CA2 and CA3 perikarya of the hippocampus (PubMed:27344443). Expressed in neurons and Purkinje cells (at the protein level) (PubMed:27344443).|||Golgi apparatus|||Interacts (via phosphorylated form and BSD domain) with AKT1; this interaction is enhanced in a mTORC2-mediated manner in response to epidermal growth factor (EGF) stimulation and activates AKT1 (PubMed:23300339).|||Membrane|||Mice appear normal and healthy (PubMed:27344443). Display no alteration on the survival or axonal elongation in primary embryonic motoneurons (PubMed:27344443). Show no alteration in total AKT phosphorylation in primary embryonic motoneurons (PubMed:27344443).|||Perikaryon|||Phosphorylated (PubMed:23300339). Phosphorylation increases in a mTORC2-mediated manner in response to epidermal growth factor (EGF) stimulation (PubMed:23300339).|||Plays a role in adipocyte differentiation by promoting mTORC2-mediated phosphorylation of AKT1 at 'Ser-473' after growth factor stimulation (PubMed:23300339).|||Postsynaptic cell membrane|||Presynaptic cell membrane|||Up-regulated during adipocyte differentiation (at protein level) (PubMed:23300339).|||axon|||dendrite|||growth cone|||perinuclear region http://togogenome.org/gene/10090:2510009E07Rik ^@ http://purl.uniprot.org/uniprot/Q6GQU0 ^@ Function|||Similarity ^@ Belongs to the UPF0524 family.|||May play a role in neuronal and neurobehavioral development. http://togogenome.org/gene/10090:Iigp1c ^@ http://purl.uniprot.org/uniprot/Q3UED7 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Or8k3b ^@ http://purl.uniprot.org/uniprot/Q7TR63 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxo4 ^@ http://purl.uniprot.org/uniprot/Q8CHQ0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer (By similarity). Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO4) formed of CUL1, SKP1, RBX1 and FBXO4 (PubMed:17081987). Interacts with TERF1; this interaction is prevented in the presence of GNL3L (PubMed:19487455). Identified in a complex with CRYAB and CCND1 (PubMed:17081987).|||Phosphorylation at Ser-11 varies during the cell cycle. It is low in resting cells and high in the S phase and the G2/M phase of the cell cycle. Phosphorylation is decreased during late G1 phase. Phosphorylation at Ser-11 is important for homodimerization and for optimal ubiquitin ligase activity towards CCND1.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:17081987, PubMed:18598945, PubMed:19767775, PubMed:29142209). Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation (PubMed:17081987, PubMed:18598945, PubMed:19767775). Recognizes TERF1 and promotes its ubiquitination together with UBE2D1 (By similarity). Promotes ubiquitination of FXR1 following phosphorylation of FXR1 by GSK3B, leading to FXR1 degradation by the proteasome (PubMed:29142209). http://togogenome.org/gene/10090:Fam205a2 ^@ http://purl.uniprot.org/uniprot/C0HKD1|||http://purl.uniprot.org/uniprot/C0HKD2|||http://purl.uniprot.org/uniprot/C0HKD3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Tspan1 ^@ http://purl.uniprot.org/uniprot/Q99J59 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||Lysosome membrane http://togogenome.org/gene/10090:Vmn1r51 ^@ http://purl.uniprot.org/uniprot/A0A0R4J266|||http://purl.uniprot.org/uniprot/Q78GE8|||http://purl.uniprot.org/uniprot/Q8VIC6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in a subset of sensory neurons located in the apical layer of the vomeronasal organ.|||Membrane|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social as well as reproductive behavior. http://togogenome.org/gene/10090:Rpl36a ^@ http://purl.uniprot.org/uniprot/P83882|||http://purl.uniprot.org/uniprot/Q5M9P1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL42 family.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Dok3 ^@ http://purl.uniprot.org/uniprot/Q14AA1|||http://purl.uniprot.org/uniprot/Q9QZK7 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DOK family. Type A subfamily.|||Cell membrane|||Constitutively tyrosine-phosphorylated.|||Cytoplasm|||DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK3 is a negative regulator of JNK signaling in B-cells through interaction with INPP5D/SHIP1. May modulate ABL1 function.|||Major, and shortest isoform.|||On IL2 stimulation, phosphorylated on C-terminal tyrosine residues possibly by Src kinases. Can also be phosphorylated by ABL1 kinase.|||On tyrosine phosphorylation, interacts with CSK and INPP5D/SHIP1 via their SH2 domains. Both Tyr-325 and Tyr-343 are required for interaction with INPP5D. Only Tyr-325 is required for interaction with CSK. Binds ABL1 through the PTB domain and in a kinase-dependent manner. Does not interact with RasGAP.|||Overexpression of DOK3 inhibits the transforming activity of v-ABL, the ABL oncogene.|||PTB domain mediates receptor interaction.|||Predominantly expressed in bone marrow, spleen and lung. Low levels in heart, brain, liver, muscle, thymus, kidney and testis. Highly expressed in B-cells and macrophages. http://togogenome.org/gene/10090:Npbwr1 ^@ http://purl.uniprot.org/uniprot/P49681 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts specifically with a number of opioid ligands. Receptor for neuropeptides B and W, which may be involved in neuroendocrine system regulation, food intake and the organization of other signals (By similarity). http://togogenome.org/gene/10090:Ngrn ^@ http://purl.uniprot.org/uniprot/Q99KS2 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neugrin family.|||Expressed in heart, brain, liver and kidney. In brain, mainly expressed in neurons rather than glial cells.|||Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA. Interacts with 16S mt-rRNA; this interaction is direct.|||Highly up-regulated in neuroblastostoma cells by RA and MG132 treatment inducing neurite outgrowth.|||Level of expression increases with embryonal development.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Mitochondrion membrane|||Nucleus|||Plays an essential role in mitochondrial ribosome biogenesis. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation of core subunits of the oxidative phosphorylation system.|||Secreted|||The N-terminus contains a duplicated region of sequence. http://togogenome.org/gene/10090:Gap43 ^@ http://purl.uniprot.org/uniprot/P06837 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neuromodulin family.|||Cell membrane|||Cytoplasm|||Expressed in the hippocampus (at protein level) (PubMed:18493953, PubMed:11573004). Expressed in the dorsal root ganglion and the spinal cord (at protein level) (PubMed:28111162).|||Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297). Interacts (via IQ domain) with calmodulin (PubMed:18493953). Binds calmodulin with a greater affinity in the absence of Ca(2+) than in its presence (By similarity).|||Palmitoylated by ZDHHC3 (PubMed:27875292). Palmitoylation is regulated by ARF6 and is essential for plasma membrane association and axonal and dendritic filopodia induction. Deacylated by LYPLA2 (By similarity).|||Perikaryon|||Phosphorylated (PubMed:18493953). Phosphorylation of this protein by a protein kinase C is specifically correlated with certain forms of synaptic plasticity (By similarity).|||Synapse|||This protein is associated with nerve growth. It is a major component of the motile 'growth cones' that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction.|||Up-regulated after memory training in radial arm maze experiments (PubMed:11573004). Up-regulated after sciatic nerve injury (PubMed:28111162).|||axon|||dendrite|||filopodium membrane|||growth cone membrane http://togogenome.org/gene/10090:Slc4a5 ^@ http://purl.uniprot.org/uniprot/D3YVG0 ^@ Similarity|||Subcellular Location Annotation ^@ Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Lateral cell membrane|||Membrane http://togogenome.org/gene/10090:Nubp1 ^@ http://purl.uniprot.org/uniprot/Q9R060 ^@ Cofactor|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP1/NBP35 subfamily.|||Binds 4 [4Fe-4S] clusters per heterotetramer. Contains two stable clusters in the N-termini of NUBP1 and two labile, bridging clusters between subunits of the NUBP1-NUBP2 heterotetramer.|||Cell projection|||Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The NUBP1-NUBP2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins (By similarity). Implicated in the regulation of centrosome duplication (PubMed:16638812, PubMed:23807208). Negatively regulates cilium formation and structure (PubMed:23807208).|||Cytoplasm|||Expressed in trachea epithelial cells, and kidney inner medullary collecting duct cells.|||Heterotetramer of 2 NUBP1 and 2 NUBP2 chains (PubMed:16638812). Interacts with KIFC1 (PubMed:16638812). Interacts with NUBP2 (PubMed:16638812). Interacts with the BBS/CCT complex subunit CCT1 (PubMed:23807208).|||High and constant expression in cycling cells. Down-regulated upon cell cycle exit and quiescence.|||NIH3T3 cells expressing reduced levels of Nubp1 show an increase in number of centrosomes per cell and an increase in the fraction of multinucleated cells.|||Nucleus|||centriole|||cilium axoneme|||cilium basal body|||microtubule organizing center http://togogenome.org/gene/10090:Zfp593 ^@ http://purl.uniprot.org/uniprot/Q9DB42 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with pre-60S ribosomal particles.|||Belongs to the ZNF593/BUD20 C2H2-type zinc-finger protein family.|||Cytoplasm|||Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome. Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity.|||The protein is largely disordered, with the exception of the zinc finger domain.|||nucleolus http://togogenome.org/gene/10090:Slc24a1 ^@ http://purl.uniprot.org/uniprot/Q91WD8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.|||Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+). Critical component of the visual transduction cascade, controlling the calcium concentration of outer segments during light and darkness. Light causes a rapid lowering of cytosolic free calcium in the outer segment of both retinal rod and cone photoreceptors and the light-induced lowering of calcium is caused by extrusion via this protein which plays a key role in the process of light adaptation.|||Cell membrane|||The uncleaved signal sequence is required for efficient membrane targeting and proper membrane integration and topology. http://togogenome.org/gene/10090:Atp5l ^@ http://purl.uniprot.org/uniprot/Q9CPQ8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATPase g subunit family.|||F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MPL (By similarity).|||Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Sptan1 ^@ http://purl.uniprot.org/uniprot/A3KGU5|||http://purl.uniprot.org/uniprot/A3KGU7|||http://purl.uniprot.org/uniprot/A3KGU9|||http://purl.uniprot.org/uniprot/B2RXX6|||http://purl.uniprot.org/uniprot/B7ZWK3|||http://purl.uniprot.org/uniprot/B9EKJ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the spectrin family.|||cell cortex|||cytoskeleton http://togogenome.org/gene/10090:Rtp3 ^@ http://purl.uniprot.org/uniprot/Q5QGU6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM7 family.|||Expressed predominantly in the liver. Not detected in the olfactory epithelium.|||Interacts with TAS2R16.|||Membrane|||Promotes functional cell surface expression of the bitter taste receptors TAS2R16 and TAS2R43. http://togogenome.org/gene/10090:Tubb6 ^@ http://purl.uniprot.org/uniprot/Q3UMM1|||http://purl.uniprot.org/uniprot/Q922F4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tubulin family.|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.|||The highly acidic C-terminal region may bind cations such as calcium.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||cytoskeleton http://togogenome.org/gene/10090:Rom1 ^@ http://purl.uniprot.org/uniprot/P32958|||http://purl.uniprot.org/uniprot/Q3UZZ7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PRPH2/ROM1 family.|||Expressed in the retina (at protein level).|||Homodimer; disulfide-linked (By similarity). Forms a homotetramer (By similarity). Forms a heterotetramer with PRPH2 (PubMed:26406599, PubMed:29961824). Homotetramer and heterotetramer core complexes go on to form higher order complexes by formation of intermolecular disulfide bonds (By similarity). Interacts with STX3 isoform 3B (PubMed:26406599). Interacts with SNAP25 (PubMed:26406599).|||Knockout mice are viable, fertile and grossly phenotypically normal (PubMed:10802659). 50% reduction in maximal rod photoreceptor response at 9 months of age (PubMed:10802659). Progressive thinning of the retinal outer nuclear layer becomes evident at 1 month of age (PubMed:10802659). Evidence of rod photoreceptor degeneration, shortened rod outer segment (ROS) length, increased ROS disk diameter, and progressive disorganization of the ROS at 1 month of age, leading to near-complete loss of organization by 2 months of age, however organization returns to near normal levels by 4 months of age (PubMed:10802659). Rod photoreceptors progressively die by apoptosis (PubMed:10802659). Knockout does not affect localization of Prph2 or Abca4 to ROS disk rims (PubMed:10802659).|||Membrane|||Photoreceptor inner segment membrane|||Photoreceptor outer segment membrane|||Plays a role in rod outer segment (ROS) morphogenesis (PubMed:10802659). May play a role with PRPH2 in the maintenance of the structure of ROS curved disks (By similarity). Plays a role in the organization of the ROS and maintenance of ROS disk diameter (PubMed:10802659). Involved in the maintenance of the retina outer nuclear layer (PubMed:10802659). http://togogenome.org/gene/10090:C8g ^@ http://purl.uniprot.org/uniprot/Q8VCG4|||http://purl.uniprot.org/uniprot/Q9DAC2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calycin superfamily. Lipocalin family.|||C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol (By similarity).|||C8 is composed of three chains: alpha, beta and gamma. The alpha and gamma chains are disulfide bonded (By similarity).|||Secreted http://togogenome.org/gene/10090:Slc5a10 ^@ http://purl.uniprot.org/uniprot/Q5SWY8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Electrogenic Na+-coupled sugar symporter that actively transports D-mannose or D-fructose at the plasma membrane, with a Na+ to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na+ electrochemical gradient set by the Na+/K+ pump. Exclusively recognizes sugar substrates having a pyranose ring with an axial hydroxyl group on carbon 2 (PubMed:23451068) (By similarity). Has likely evolved to enable renal reabsorption of D-mannose, an important constituent of oligosaccharide chains of glycoproteins. Contributes to dietary D-fructose reabsorption from glomerular filtrate across the brush border of the kidney (PubMed:23451068) (By similarity).|||Mice are born at the expected Mendelian rate and have no apparent morphological abnormalities. In response to long-term fructose consumption, they develop exacerbated hepatic steatosis associated with massive urinary fructose excretion and increased hepatic triglyceride levels.|||Predominantly expressed at high levels in kidney. Very low expression is detected in testes. http://togogenome.org/gene/10090:Apod ^@ http://purl.uniprot.org/uniprot/P51910 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ APOD occurs in the macromolecular complex with lecithin-transport and binding of bilin. Appears to be able to transport a variety of ligands in a number of different contexts.|||Belongs to the calycin superfamily. Lipocalin family.|||Highest levels of expression in brain, testis, virgin mammary gland and salivary gland. Moderate levels in skeletal muscle, lactating mammary gland and thymus. Low levels in lung and lymph node. No expression in kidney, pancreas, liver or spleen.|||Homodimer.|||Secreted http://togogenome.org/gene/10090:Vcam1 ^@ http://purl.uniprot.org/uniprot/Q3UPN1 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Slc9c1 ^@ http://purl.uniprot.org/uniprot/Q6UJY2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Interacts with soluble adenylyl cyclase (sAC).|||Mice are normal but males are sterile. Male sterility is due to defects in sperm motility inability to fertilize intact eggs. Moreover, spermatozoa fail to develop the cAMP-dependent protein tyrosine phosphorylation that coincides with the functional maturation occurring upon incubation in capacitating conditions in vitro. cAMP analogs almost completely rescue the motility and infertility phenotypes.|||Sperm-specific sodium/hydrogen exchanger involved in intracellular pH regulation of spermatozoa. Required for sperm motility and fertility. Involved in sperm cell hyperactivation, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for the expression and bicarbonate regulation of the soluble adenylyl cyclase (sAC).|||Testis-specific. Specifically present in the principal piece of sperm tail (at protein level).|||The ion transport-like region is related to the membrane segments of voltage-gated ion channels. Its function is unknown.|||flagellum membrane http://togogenome.org/gene/10090:Hycc1 ^@ http://purl.uniprot.org/uniprot/Q6P9N1 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Hyccin family.|||Cell membrane|||Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. HYCC1 plays a key role in oligodendrocytes formation, a cell type with expanded plasma membrane that requires generation of PtdIns(4)P. Its role in oligodendrocytes formation probably explains its importance in myelination of the central and peripheral nervous system. May also have a role in the beta-catenin/Lef signaling pathway.|||Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2). Interacts with TTC7 (TTC7A or TTC7B), interaction is direct.|||Down-regulated by beta-catenin.|||No visible phenotype. Lysates from total brain and optic nerve (a pure white matter tract) display a selective decrease of Ttc7a and Efr3a protein levels.|||Predominantly expressed in the central nervous system, where it is found in neurons but not in myelinating cells. Lower abundance is observed in peripheral neurons, where it is detectable only at early postnatal ages (PubMed:22461884). Expressed in both oligodendrocytes and neurons (PubMed:26571211).|||cytosol http://togogenome.org/gene/10090:Fhl2 ^@ http://purl.uniprot.org/uniprot/O70433 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in heart but also detectable in brain and skeletal muscle.|||Interacts with ZNF638 and TTN/titin. Interacts with E4F1. Interacts with GRB7. Interacts with SIRT1 and FOXO1. Interacts with CEFIP (By similarity). Interacts with calcineurin (PubMed:22851699). Interacts with FOXK1 (PubMed:20013826).|||May function as a molecular transmitter linking various signaling pathways to transcriptional regulation. Negatively regulates the transcriptional repressor E4F1 and may function in cell growth. Inhibits the transcriptional activity of FOXO1 and its apoptotic function by enhancing the interaction of FOXO1 with SIRT1 and FOXO1 deacetylation (By similarity). Negatively regulates the calcineurin/NFAT signaling pathway in cardiomyocytes (PubMed:22851699).|||Nucleus|||The third LIM zinc-binding mediates interaction with E4F1.|||Up-regulated in hearts exposed to isoproterenol (at protein level).|||Z line http://togogenome.org/gene/10090:Cspg4 ^@ http://purl.uniprot.org/uniprot/Q8VHY0 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Cell surface|||Expressed in microcascular pericytes and not endothelial cells.|||Interacts with ITGA4 through its chondroitin sulfate glycosaminoglycan. Interacts with BCAR1, CDC42 and ACK1. Interacts with MMP16. Interacts with the first PDZ domain of MPDZ. Interacts with PRKCA. Interacts with LGALS3 and the integrin composed of ITGB1 and ITGA3. Binds TNC, laminin-1, COL5A1 and COL6A2. Interacts with PLG and angiostatin. Binds FGF2 and PDGFA (By similarity). Interacts with GRIP1, GRIP2 and GRIA2. Forms a ternary complex with GRIP1 and GRIA2.|||Mice are unresponsive to PDGF-AA through PDGF-alpha receptor.|||O-glycosylated; contains glycosaminoglycan chondroitin sulfate which are required for proper localization and function in stress fiber formation. Involved in interaction with MMP16 and ITGA4 (By similarity).|||Phosphorylation by PRKCA regulates its subcellular location and function in cell motility.|||Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis. May also inhibit neurite outgrowth and growth cone collapse during axon regeneration. Cell surface receptor for collagen alpha 2(VI) which may confer cells ability to migrate on that substrate. Binds through its extracellular N-terminus growth factors, extracellular matrix proteases modulating their activity. May regulate MPP16-dependent degradation and invasion of type I collagen participating in melanoma cells invasion properties. May modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. Functions also as a signal transducing protein by binding through its cytoplasmic C-terminus scaffolding and signaling proteins. May promote retraction fiber formation and cell polarization through Rho GTPase activation. May stimulate alpha-4, beta-1 integrin-mediated adhesion and spreading by recruiting and activating a signaling cascade through CDC42, ACK1 and BCAR1. May activate FAK and ERK1/ERK2 signaling cascades.|||Valuable marker for several incompletely differentiated precursor cells.|||lamellipodium membrane http://togogenome.org/gene/10090:1700040F15Rik ^@ http://purl.uniprot.org/uniprot/A0A087WRK1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Htr2b ^@ http://purl.uniprot.org/uniprot/Q02152 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1426253). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:1426253, PubMed:16940156). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and downstream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores (By similarity). Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity (PubMed:16940156, PubMed:18337424). May play a role in the perception of pain (PubMed:21273425). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development (PubMed:10944220, PubMed:11413089). Protects cardiomyocytes against apoptosis (PubMed:12738797). Plays a role in the adaptation of pulmonary arteries to chronic hypoxia (PubMed:12244304). Plays a role in vasoconstriction (PubMed:12244304, PubMed:23346101). Required for normal osteoblast function and proliferation, and for maintaining normal bone density (PubMed:17846081). Required for normal proliferation of the interstitial cells of Cajal in the intestine (PubMed:19941613).|||Interacts (via C-terminus) with MPDZ.|||Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.|||Partial embryonic and perinatal lethality, due to heart ventricle hypoplasia and impaired proliferative capacity of heart myocytes. Mutant mice that survive into adulthood have a decreased heart weight relative to body weight. They display dilated cardiomyopathy with a loss of ventricular mass, due to a reduction in the number and size of cardiomyocytes. The myocardium from mutant mice displays abnormal organization of the contractile elements, with an irregular array of sarcomeric myofibrils and abnormally wide Z bands. In addition, heart muscle mitochondria display structural and functional defects. Mutant mice do not respond to chronic exposure to low oxygen levels by remodeling of their lung arteries, unlike wild-type mice, and as a consequence, do not develop increased right ventricular systolic pressure in response to chronic hypoxia. Adult mutant female mice display reduced bone density that worsens with age. Osteopenia is due to reduced proliferation and delayed differentiation of osteoblasts and reduced calcium incorporation by osteoblasts (PubMed:17846081). In addition, mutant mice display a reduced number of proliferating interstitial cells of Cajal in the myenteric plexus in jejunum muscle, and a reduced number of interstitial cells of Cajal in the deep muscular plexus (PubMed:19941613). Mutant mice also show increased locomotor activity in a novel environment, compared to the wild-type. Unlike the wild-type, they do not respond to the drug 3,4-methylenedioxymethamphetamine with increased locomotion and increased 5-hydroxytryptamine and dopamine levels in the brain (PubMed:18337424).|||Ubiquitous. Detected in intestine, heart, skeletal muscle, testis, urinary bladder, stomach, liver, lung, brain and kidney. Detected in osteoblasts. Detected in the raphe nucleus in the brain, in dorsal root ganglion neurons, the brain stem, cerebellum and spinal cord. Detected in interstitial cells of Cajal in the small intestine.|||synaptosome http://togogenome.org/gene/10090:Esrra ^@ http://purl.uniprot.org/uniprot/O08580 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by diethylstilbestrol (DES) and estradiol in the uterus.|||Belongs to the nuclear hormone receptor family. NR3 subfamily.|||Binds DNA as a monomer or a homodimer. Interacts (via the AF2 domain) with coactivator PPARGC1A (via the L3 motif); the interaction greatly enhances transcriptional activity of genes involved in energy metabolism. Interacts with PIAS4; the interaction enhances sumoylation (By similarity). Interacts with MAPK15; promotes re-localization of ESRRA to the cytoplasm through a XPO1-dependent mechanism then inhibits ESRRA transcriptional activity (PubMed:21190936).|||Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle (By similarity).|||Cytoplasm|||Expressed in an organ specific manner through mid- to late embryonic development with persistent high-level expression in brown adipose tissue and intestinal mucosa.|||Most highly expressed in kidney, heart, and brown adipocytes. Also found in uterus, cervix and vagina.|||No visible phenotype; mice are viable, fertile and display no gross anatomical alterations, with the exception of reduced body weight and peripheral fat deposits. Mice are resistant to a high-fat diet-induced obesity. Cardiomyocyte-specific double konckout for ESRRA and ESRRG are slower at gaining weight, smaller and shorter from 5 to 7 days of age compared to controls. They show decreased absolute weight of most internal organs except the heart. They have about 70% decreased plasma IGF1 levels but normal plasma growth hormone levels. At 14-15 days, mutants develop lethal dilated cardiomyopathy and heart failure (PubMed:28572090).|||Nucleus|||Phosphorylation on Ser-19 enhances sumoylation on Lys-14 increasing repression of transcriptional activity.|||Reversibly acetylated. Acetylation by PCAF/KAT2 at Lys-129, Lys-138, Lys-160 and Lys-162 and PCAF/KAT2 decreases transcriptional activity probably by inhibiting DNA-binding activity; deacetylation involves SIRT1 and HDAC8 and increases DNA-binding (By similarity).|||Sumoylated with SUMO2. Main site is Lys-14 which is enhanced by phosphorylation on Ser-19, cofactor activation, and by interaction with PIAS4. Sumoylation enhances repression of transcriptional activity, but has no effect on subcellular location nor on DNA binding (By similarity). http://togogenome.org/gene/10090:Stc2 ^@ http://purl.uniprot.org/uniprot/O88452|||http://purl.uniprot.org/uniprot/Q5SS12 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the stanniocalcin family.|||Found in a variety of tissues including skeletal muscle, small intestine, kidney, liver and brain.|||Has an anti-hypocalcemic action on calcium and phosphate homeostasis.|||Homodimer; disulfide-linked.|||Secreted http://togogenome.org/gene/10090:Padi4 ^@ http://purl.uniprot.org/uniprot/Q9Z183 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.|||Belongs to the protein arginine deiminase family.|||Binds 5 Ca(2+) ions per subunit.|||Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance (PubMed:15339660, PubMed:32528174). Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci) (PubMed:15339660). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance (PubMed:24463520, PubMed:32528174). Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci (PubMed:20733033, PubMed:23650392). Required for the formation of neutrophil extracellular traps (NETs); NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (PubMed:20733033, PubMed:32528174). Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription (By similarity). Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1 (By similarity).|||Cytoplasm|||Cytoplasmic granule|||Expressed in pluripotent embryonic stem and induced pluripotent stem cells but not multipotent neural stem cells.|||Mice survive to adulthood and do not display detectable physical abnormality (PubMed:20733033). However, mice were born at a rate lower than predicted by the Mendelian ratio and display defects in innate immune response (PubMed:20733033). Impaired formation of neutrophil extracellular traps (NETs) (PubMed:20733033, PubMed:32528174). Mice are more susceptible to bacterial infection: neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs (PubMed:20733033). Less than 10% of deficient mice produce a thrombus 48 hours after inferior vena cava stenosis whereas 90% of wild-type mice do (PubMed:23650392).|||Nucleus|||Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family. http://togogenome.org/gene/10090:Clip1 ^@ http://purl.uniprot.org/uniprot/D3Z2Z1|||http://purl.uniprot.org/uniprot/D3Z3M7|||http://purl.uniprot.org/uniprot/F8WIA1|||http://purl.uniprot.org/uniprot/Q922J3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking.|||Cytoplasm|||Cytoplasmic vesicle membrane|||Expressed in the testes (at protein level).|||Interacts with MTOR; phosphorylates and regulates CLIP1. Interacts (via CAP-Gly domains) with tubulin. Interacts with SLAIN2. Interacts with TUBA1B, MAPRE1 and MAPRE3. Interacts (via zinc finger) with DCTN1 (By similarity). Binds preferentially to tyrosinated microtubules, and only marginally to detyrosinated microtubules (PubMed:16954346).|||Intramolecular interaction between the zinc finger domain and the CAP-Gly domains may inhibit interaction with tubulin.|||Phosphorylated (PubMed:26972003). Phosphorylation induces conformational changes by increasing the affinity of the N-terminus for C-terminus, resulting in inhibition of its function thus decreasing its binding to microtubules and DCTN1. Exhibits a folded, autoinhibited conformation when phosphorylated and an open conformation when dephosphorylated with increased binding affinity to microtubules and DCTN1. Phosphorylation regulates its recruitment to tyrosinated microtubules and the recruitment of vesicular cargo to microtubules in neurons. Phosphorylation by MTOR may positively regulate CLIP1 association with microtubules (By similarity).|||cytoskeleton|||ruffle http://togogenome.org/gene/10090:Pklr ^@ http://purl.uniprot.org/uniprot/E9Q509|||http://purl.uniprot.org/uniprot/G3X925|||http://purl.uniprot.org/uniprot/Q3UEH4|||http://purl.uniprot.org/uniprot/Q3UEI4 ^@ Similarity ^@ Belongs to the pyruvate kinase family. http://togogenome.org/gene/10090:Vmn2r45 ^@ http://purl.uniprot.org/uniprot/L7N2B5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Hk2 ^@ http://purl.uniprot.org/uniprot/O08528 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hexokinase family.|||Catalyzes the phosphorylation of hexose, such as D-glucose and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-fructose 6-phosphate, respectively) (By similarity). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity). Plays a key role in maintaining the integrity of the outer mitochondrial membrane by preventing the release of apoptogenic molecules from the intermembrane space and subsequent apoptosis (PubMed:18350175).|||Embryonic lethality around E7.5 stage probably caused by the absence of hexokinase activity.|||Hexokinase activity is specifically inhibited by 2,6-disubstituted glucosamines.|||Mitochondrion outer membrane|||Monomer (By similarity). Interacts with TIGAR; the interaction increases hexokinase activity in a hypoxia- and HIF1A-dependent manner (By similarity).|||Predominantly expressed in skeletal muscle, heart and adipose tissues.|||The N- and C-terminal halves of the protein contain a hexokinase domain. In contrast to hexokinase-1 and -3 (HK1 and HK3, respectively), both hexokinase domains display catalytic activity. The region connecting the two hexokinase domains is required for the catalytic activity of the N-terminal hexokinase domain. The N-terminal half regulates stability of the whole enzyme.|||cytosol http://togogenome.org/gene/10090:Kat5 ^@ http://purl.uniprot.org/uniprot/A0A494BAP7|||http://purl.uniprot.org/uniprot/Q3UJQ1|||http://purl.uniprot.org/uniprot/Q8CHK4 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acyltransferase and acetyltransferase activities are activated by phosphorylation and autoacetylation (PubMed:22539723). Autoacetylation activates the histone acetyltransferase activity (By similarity).|||Autoacetylated (By similarity). Autoacetylation is required for histone acetyltransferase activity (By similarity). Autoacetylation at Lys-327 is facilitated by interaction with EP300/p300: it prevents ubiquitination and subsequent degradation by the proteasome and promotes acetylation of target proteins (By similarity). Deacetylated by HDAC3 and SIRT1 (By similarity). Deacetylation by HDAC3 promotes its ubiquitination and cytoplasmic localization (By similarity).|||Belongs to the MYST (SAS/MOZ) family.|||Catalytic subunit of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H2A and H4 (PubMed:28694333, PubMed:30297459, PubMed:32542325). Histone acetylation alters nucleosome-DNA interactions and promotes interaction of the modified histones with other proteins which positively regulate transcription (By similarity). The NuA4 histone acetyltransferase complex is required for the activation of transcriptional programs associated with proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:17728759). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR): the complex inhibits TP53BP1 binding to chromatin via MBTD1, which recognizes and binds histone H4 trimethylated at 'Lys-20' (H4K20me), and KAT5 that catalyzes acetylation of 'Lys-15' of histone H2A (H2AK15ac), thereby blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks (PubMed:30297459). Also involved in DSB repair by mediating acetylation of 'Lys-5' of histone H2AX (H2AXK5ac), promoting NBN/NBS1 assembly at the sites of DNA damage (By similarity). The NuA4 complex plays a key role in hematopoietic stem cell maintenance and is required to maintain acetylated H2A.Z/H2AZ1 at MYC target genes (PubMed:32542325). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone hyperacetylation is required for histone replacement during the transition from round to elongating spermatids (PubMed:28694333). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (By similarity). Also acetylates non-histone proteins, such as BMAL1, ATM, AURKB, CHKA, CGAS, ERCC4/XPF, LPIN1, NDC80/HEC1, NR1D2, RAN, SOX4, FOXP3, ULK1 and RUBCNL/Pacer (PubMed:22539723, PubMed:24835996, PubMed:31294688). Directly acetylates and activates ATM (By similarity). Promotes nucleotide excision repair (NER) by mediating acetylation of ERCC4/XPF, thereby promoting formation of the ERCC4-ERCC1 complex (By similarity). Relieves NR1D2-mediated inhibition of APOC3 expression by acetylating NR1D2 (By similarity). Acts as a regulator of regulatory T-cells (Treg) by catalyzing FOXP3 acetylation, thereby promoting FOXP3 transcriptional repressor activity (PubMed:24835996). Involved in skeletal myoblast differentiation by mediating acetylation of SOX4 (PubMed:26291311). Catalyzes acetylation of APBB1/FE65, increasing its transcription activator activity (By similarity). Promotes transcription elongation during the activation phase of the circadian cycle by catalyzing acetylation of BMAL1, promoting elongation of circadian transcripts (PubMed:31294688). Together with GSK3 (GSK3A or GSK3B), acts as a regulator of autophagy: phosphorylated at Ser-86 by GSK3 under starvation conditions, leading to activate acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:22539723). Acts as a regulator of the cGAS-STING innate antiviral response by catalyzing acetylation the N-terminus of CGAS, thereby promoting CGAS DNA-binding and activation (By similarity). Also regulates lipid metabolism by mediating acetylation of CHKA or LPIN1 (PubMed:29765047). Promotes lipolysis of lipid droplets following glucose deprivation by mediating acetylation of isoform 1 of CHKA, thereby promoting monomerization of CHKA and its conversion into a tyrosine-protein kinase (By similarity). Acts as a regulator of fatty-acid-induced triacylglycerol synthesis by catalyzing acetylation of LPIN1, thereby promoting the synthesis of diacylglycerol (PubMed:29765047). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA) and 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), and is able to mediate protein crotonylation and 2-hydroxyisobutyrylation, respectively (By similarity). Acts as a key regulator of chromosome segregation and kinetochore-microtubule attachment during mitosis by mediating acetylation or crotonylation of target proteins (By similarity). Catalyzes acetylation of AURKB at kinetochores, increasing AURKB activity and promoting accurate chromosome segregation in mitosis (By similarity). Acetylates RAN during mitosis, promoting microtubule assembly at mitotic chromosomes (By similarity). Acetylates NDC80/HEC1 during mitosis, promoting robust kinetochore-microtubule attachment (By similarity). Catalyzes crotonylation of MAPRE1/EB1, thereby ensuring accurate spindle positioning in mitosis (By similarity).|||Chromosome|||Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6 (PubMed:32542325). KAT5/TIP60, EPC1, and ING3 together constitute a minimal HAT complex termed Piccolo NuA4 (By similarity). The NuA4 complex interacts with MYC (By similarity). Interacts with ATM (By similarity). Interacts with JADE1 (By similarity). Interacts with PLA2G4A/CPLA2, EDNRA and HDAC7 (By similarity). Interacts with the cytoplasmic tail of APP and APBB1/FE65 (By similarity). Interacts with TRIM24 and TRIM68 (By similarity). Forms a complex with SENP6 and UBE2I in response to UV irradiation (By similarity). Identified in a complex with HINT1 (By similarity). Interacts with ATF2 and CUL3 (By similarity). Interacts with NR1D2 (via N-terminus) (By similarity). Component of a SWR1-like complex (By similarity). Interacts with FOXP3 (PubMed:19696312). Interacts with ZBTB49 (By similarity). Interacts with SRF (PubMed:16597624). Interacts with ATF3; promoting autoacetylation and deubiquitination by USP7 (By similarity). Interacts with EP300/p300; interaction promotes KAT5 autoacetylation (By similarity). Interacts with PRKDC; interaction is impaired following KAT5 sumoylation (By similarity).|||Cytoplasm|||Embryonic lethality before implantation (PubMed:17728759). Conditional deletion leads to rapid hematopoietic stem cell loss in both fetal and adult stages (PubMed:32542325). Conditional deletion at postnatal day 15 leads to impaired spermatid development: testes are smaller and show defects in the transition from the transition from round to elongating spermatids (PubMed:28694333). Defects in spermatid development is probably caused by impaired acetylation of histones that affects histone replacement (PubMed:28694333). Conditional deletion in response to DNA damage leads to impaired homologous recombination (HR)repair in response to DNA double-strand breaks (DSBs), associated with increased non-homologous end joining (NHEJ)-mediated repair mediated by TP53BP1 (PubMed:30297459).|||Expressed in testis, heart, brain, kidney and liver. Weakly expressed in lung.|||Mice lacking isoform 5 die during mid-gestation (around embryonic day 11.5) (PubMed:30297694). Prior to developmental arrest, embryos display defects in heart and neural tube (PubMed:30297694). Specification of cardiac and neural cell fates is first normal; however, cell division and survival are impaired in heart and neural tube, respectively (PubMed:30297694).|||Nucleus|||Phosphorylated on Ser-86 and Ser-90; enhanced during G2/M phase (PubMed:22539723, PubMed:30297459, PubMed:34608293). The phosphorylated form has a higher activity (PubMed:30297459, PubMed:34608293). Phosphorylation at Ser-90 by CDK1 or CDK9 is a prerequisite for phosphorylation at Ser-86 by GSK3 (PubMed:34608293). Phosphorylation at Ser-86 by GSK3 (GSK3A or GSK3B) activates acetyltransferase and acyltransferase activity (PubMed:22539723, PubMed:30297459). Phosphorylation at Ser-90 by CDK9 promotes KAT5 recruitment to chromatin (By similarity). Phosphorylation by VRK1 following DNA damage promotes KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429).|||Sumoylated by UBE2I at Lys-430 and Lys-451, leading to increase of its histone acetyltransferase activity in UV-induced DNA damage response, as well as its translocation to nuclear bodies (By similarity). Sumoylation with SUMO2 by PIAS4 at Lys-430 promotes repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity). Sumoylation by PIAS4 impairs interaction with PRKDC, inhibiting non-homologous end joining (NHEJ)-mediated repair of DSBs, thereby facilitating HR (By similarity). Desumoylated by SENP3 (By similarity).|||Ubiquitinated by MDM2, leading to its proteasome-dependent degradation (By similarity). Ubiquitination is prevented by autoacetylation at Lys-327 (By similarity). Ubiquitinated following deacetylation by HDAC3, leading to cytoplasmic localization (By similarity). Deubiquitinated by USP7 following interaction with ATF3, promoting its stabilization (By similarity).|||kinetochore|||nucleolus|||perinuclear region|||spindle pole http://togogenome.org/gene/10090:Ube2g1 ^@ http://purl.uniprot.org/uniprot/P62254|||http://purl.uniprot.org/uniprot/Q5F239 ^@ Function|||PTM|||Similarity ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. May be involved in degradation of muscle-specific proteins. Mediates polyubiquitination of CYP3A4.|||Autoubiquitinated.|||Belongs to the ubiquitin-conjugating enzyme family. http://togogenome.org/gene/10090:Fn3k ^@ http://purl.uniprot.org/uniprot/Q9ER35 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the fructosamine kinase family.|||Expressed in red blood cells, brain, heart, kidney and muscle (PubMed:15331600). Lower expression is observed in liver (PubMed:15331600). Not expressed in lung, spleen, testis and thymus (PubMed:15331600).|||Fructosamine-3-kinase involved in protein deglycation by mediating phosphorylation of fructoselysine residues on glycated proteins, to generate fructoselysine-3 phosphate (PubMed:11016445, PubMed:16819943). Fructoselysine-3 phosphate adducts are unstable and decompose under physiological conditions (By similarity). Involved in intracellular deglycation in erythrocytes and pancreatic islets (PubMed:16819943, PubMed:20009024). Involved in the response to oxidative stress by mediating deglycation of NFE2L2/NRF2, glycation impairing NFE2L2/NRF2 function (PubMed:31398338). Also able to phosphorylate psicosamines and ribulosamines (By similarity).|||Mice are viable and healthy and show normal blood glucose and serum fructosamine levels (PubMed:16819943). They however display increased protein glycation levels in cells such as erythrocytes and pancreatic islets (PubMed:16819943, PubMed:20009024). Increased levels of protein glycation levels do not affect the maintenance and function of pancreatic islets (PubMed:20009024).|||Monomer. http://togogenome.org/gene/10090:Slc35f2 ^@ http://purl.uniprot.org/uniprot/Q7TML3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC35F solute transporter family.|||Membrane|||Putative solute transporter. http://togogenome.org/gene/10090:Kat7 ^@ http://purl.uniprot.org/uniprot/Q1AJD0|||http://purl.uniprot.org/uniprot/Q3TD41|||http://purl.uniprot.org/uniprot/Q3UGF2|||http://purl.uniprot.org/uniprot/Q5SVQ0 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoacetylation at Lys-434 is required for proper function.|||Belongs to the MYST (SAS/MOZ) family.|||Catalytic subunit of histone acetyltransferase HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby regulating various processes, such as gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance and embryonic development (PubMed:21753189, PubMed:21149574, PubMed:23319590, PubMed:27733580, PubMed:31827282). Some complexes also catalyze acetylation of histone H4 at 'Lys-5', 'Lys-8' and 'Lys-12' (H4K5ac, H4K8ac and H4K12ac, respectively), regulating DNA replication initiation, regulating DNA replication initiation (By similarity). Specificity of the HBO1 complexes is determined by the scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE (JADE1, JADE2 and JADE3) scaffold direct KAT7/HBO1 specificity towards histone H4 (By similarity). H3K14ac promotes transcriptional elongation by facilitating the processivity of RNA polymerase II (PubMed:31827282). Acts as a key regulator of hematopoiesis by forming a complex with BRD1/BRPF2, directing KAT7/HBO1 specificity towards H3K14ac and promoting erythroid differentiation (By similarity). H3K14ac is also required for T-cell development (PubMed:27733580). KAT7/HBO1-mediated acetylation facilitates two consecutive steps, licensing and activation, in DNA replication initiation: H3K14ac facilitates the activation of replication origins, and histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac) facilitates chromatin loading of MCM complexes, promoting DNA replication licensing (By similarity). Acts as a positive regulator of centromeric CENPA assembly: recruited to centromeres and mediates histone acetylation, thereby preventing centromere inactivation mediated by SUV39H1, possibly by increasing histone turnover/exchange (By similarity). Involved in nucleotide excision repair: phosphorylation by ATR in response to ultraviolet irradiation promotes its localization to DNA damage sites, where it mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites (By similarity). Acts as an inhibitor of NF-kappa-B independently of its histone acetyltransferase activity (By similarity).|||Chromosome|||Component of the HBO1 complex composed of KAT7/HBO1, MEAF6, ING4 or ING5, and one scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE scaffold (JADE1, JADE2 and JADE3) mediate acetylation of histone H4 (PubMed:21753189, PubMed:31827282). Interacts with MCM2 and ORC1 (By similarity). Interacts with the androgen receptor (AR) in the presence of dihydrotestosterone (By similarity). Interacts with CDT1 (By similarity). Interacts with MAP2K1 and CUL1 (PubMed:23319590). Interacts with p53/TP53; leading to inhibit histone acetyltransferase activity (By similarity).|||Embryonic lethality caused by a strong reduction of histone H3 'Lys-14' acetylation (H3K14ac) (PubMed:21149574). Development is arrested at the 10-somite stage (PubMed:21149574). Blood vessels, mesenchyme, and somites are disorganized (PubMed:21149574). No defects in DNA replication or cell proliferation are observed (PubMed:21149574). Conditional mice lacking Kat7 in thymocytes display normal alpha-beta T-cells but show impaired development of peripheral CD4(+) or CD8(+) T-cells (PubMed:27733580).|||Expressed ubiquitously in the embryonic and extraembryonic tissues (PubMed:21149574). High levels are present in the chorionic plate (8.5 dpc and 9.5 dpc) as well as in and around the foregut and hindgut regions (9.5 dpc) (PubMed:21149574).|||Histone acetyltransferase activity is inhibited by GMNN in the context of a complex with CDT1, inhibiting histone H4 acetylation and DNA replication licensing.|||Nucleus|||Phosphorylated at Ser-52 and Ser-55 by ATR in response to DNA damage, promoting its ubiquitination by the CRL4(DDB2) complex and subsequent degradation. Phosphorylation at Ser-52 and Ser-55 by ATR in response to ultraviolet-induced DNA, promotes localization to DNA damage sites. Phosphorylation at Ser-59 by PLK1 during mitosis seems important for prereplicative complex formation and DNA replication licensing, and requires prior phosphorylation at Thr-87 and Thr-90 by CDK1 (By similarity). Phosphorylated by MAP2K1, which accelerates its degradation (PubMed:23319590).|||Plays a central role in the maintenance of leukemia stem cells in acute myeloid leukemia (AML) (PubMed:31827282). Acts by mediating acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby facilitating the processivity of RNA polymerase II to maintain the high expression of key genes, such as HOXA9 and HOXA10 that help to sustain the functional properties of leukemia stem cells (PubMed:31827282).|||The C2HC MYST-type zinc finger is required for interaction with MCM2 and ORC1.|||The N-terminus is involved in transcriptional repression, while the C-terminus mediates AR-interaction.|||Ubiquitinated at Lys-340, leading to proteasomal degradation. Ubiquitinated by the CRL4(DDB2) complex following phosphorylation by ATR, leading to its subsequent degradation.|||Widely expressed in adult tissues.|||centromere|||cytosol http://togogenome.org/gene/10090:Qdpr ^@ http://purl.uniprot.org/uniprot/Q8BVI4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Catalyzes the conversion of quinonoid dihydrobiopterin into tetrahydrobiopterin.|||Homodimer. http://togogenome.org/gene/10090:Ctsl ^@ http://purl.uniprot.org/uniprot/P06797|||http://purl.uniprot.org/uniprot/Q543M3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the peptidase C1 family.|||Dimer of a heavy and a light chain linked by disulfide bonds (Probable). Interacts with Long isoform of CD74/Ii chain; the interaction stabilizes the conformation of mature CTSL (PubMed:11483509, PubMed:12417635).|||During export along the endocytic pathway, pro-CTSL undergoes several proteolytic cleavages to generate the CTSL single-chain and two-chain mature forms, composed of a heavy chain linked to a light chain by disulfide bonds (PubMed:11483509). Autocleavage; produces the single-chain CTSL after cleavage of the propeptide. The cleavage can be intermolecular (By similarity).|||Enlarged thyroid follicles, reduced extension of the thyroid epithelium and increased levels of Tg/thyroglobulin in the thyroid follicles. Lysosomes are enlarged and CTSB/cathepsin B is mis-localized to the apical membrane of thyroid epithelial cells. Serum levels of thyroid hormone thyroxine (T4) are reduced. The phenotype is more severe in CTSK/cathepsin K and CTSL double knockout mice (PubMed:12782676). Mutants possess reduced levels of Met-enkephalin in brain (PubMed:12869695). Mice show impaired CD4(+) T cell selection (PubMed:12021314). They have reduced numbers of CD4(+) T cells in the thymus and periphery and CD8(+) T cells relatively increased (PubMed:9545226). One-year-old mutant mice show ventricular and atrial enlargement associated with a comparatively small increase in relative heart weight and severely impaired myocardial contraction. They show interstitial fibrosis and pleomorphic nuclei (PubMed:11972068). Cardiomyocytes contain multiple large and apparently fused lysosomes characterized by storage of electron-dense heterogeneous material (PubMed:11972068). Mutants have delayed hair follicle morphogenesis and late onset of the first catagen stage. Their skin show mild epidermal hyperplasia and hyperkeratosis, severe hyperplasia of the sebaceous glands, and structural alterations of hair follicles (PubMed:12163394).|||Expressed in thymus, kidney and liver (PubMed:9545226). Expressed in thyroid epithelial cells. Expressed in cortical thymic epithelial cells (PubMed:9545226). Expressed by antigen presenting cells (APCs) such as dendritic cells and macrophages (PubMed:11483509, PubMed:12417635).|||Long isoform of CD74/Ii chain stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of APCs (PubMed:11483509, PubMed:12417635). IFNG enhances the conversion into the CTSL mature and active form (PubMed:11483509). Inhibited by CST6. Inhibited by the glycopeptide antibiotic teicoplanin. Inhibited by amantadine (By similarity).|||Lysosome|||Secreted|||Thiol protease important for the overall degradation of proteins in lysosomes (Probable). Involved in the solubilization of cross-linked TG/thyroglobulin and in the subsequent release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:12782676). In neuroendocrine chromaffin cells secretory vesicles, catalyzes the prohormone proenkephalin processing to the active enkephalin peptide neurotransmitter (PubMed:12869695). In thymus, regulates CD4(+) T cell positive selection by generating the major histocompatibility complex class II (MHCII) bound peptide ligands presented by cortical thymic epithelial cells (PubMed:12021314). Also mediates invariant chain processing in cortical thymic epithelial cells (PubMed:9545226). Major elastin-degrading enzyme at neutral pH. Accumulates as a mature and active enzyme in the extracellular space of antigen presenting cells (APCs) to regulate degradation of the extracellular matrix in the course of inflammation (PubMed:12417635). Secreted form generates endostatin from COL18A1 (PubMed:10716919). Critical for cardiac morphology and function (PubMed:11972068). Plays an important role in hair follicle morphogenesis and cycling, as well as epidermal differentiation (PubMed:12163394). Required for maximal stimulation of steroidogenesis by TIMP1 (By similarity).|||chromaffin granule|||extracellular space http://togogenome.org/gene/10090:Or12d17 ^@ http://purl.uniprot.org/uniprot/Q8VG96 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnfrsf21 ^@ http://purl.uniprot.org/uniprot/Q9EPU5 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with TRADD (By similarity). Interacts with NGFR. Interacts with CASP8 (By similarity). Interacts with N-APP (PubMed:19225519).|||Cell membrane|||Detected in spleen B-cells (at protein level). Ubiquitous. Highly expressed in adult spleen, thymus, testis, prostate, ovary, small intestine, colon, brain, lung and kidney, and in fetal brain, liver and lung. Detected at lower levels in adult peripheral blood leukocytes, lung, and in fetal muscle, heart, kidney, small intestine and skin. Detected in T-cells, B-cells and monocytes. In T-cells expression is highest in Th0 cells, intermediate in Th2 cells and lower in Th1 cells. Expressed at low levels in proliferating progenitors in the spinal cord, but is highly expressed by differentiating neurons within the spinal cord and adjacent dorsal root ganglia. Expressed by developing neurons as they differentiate and enter a pro-apoptotic state. Expressed by both cell bodies and axons.|||It is uncertain whether Met-1 or Met-25 is the initiator.|||No visible phenotype. Mice are born at the expected Mendelian rate, are viable and fertile. Mutant mice display an increased number of T-cells in the peripheral blood, but only a minor increase of the number of T-cells in spleen and thymus. T-cells from mutant mice show increased proliferative responses to antigens and produce higher levels of IL4, IL5, IL10, IL13 and IFNG. Mutant mice have normal serum levels of IgG and IgM in the absence of antigen, but produce higher levels of IgG, IgM and IgM in response to antigens. Likewise, B-cells from mutant mice display increased proliferation and decreased apoptosis in response to antigens. Mutant mice show increased levels of mature oligodendrocytes, decreased levels of apoptotic oligodendrocytes and increased myelination. Mutant mice are not susceptible to neuronal apoptosis triggered by exposure to amyloid peptides derived from APP.|||Oxidized in response to reactive oxygen species (ROS), leading to endocytosis.|||Promotes apoptosis, possibly via a pathway that involves the activation of NF-kappa-B (PubMed:11485735, PubMed:11714751, PubMed:12515813, PubMed:19225519, PubMed:21725297, PubMed:23559013). Can also promote apoptosis mediated by BAX and by the release of cytochrome c from the mitochondria into the cytoplasm (By similarity). Plays a role in neuronal apoptosis, including apoptosis in response to amyloid peptides derived from APP, and is required for both normal cell body death and axonal pruning (PubMed:19225519). Trophic-factor deprivation triggers the cleavage of surface APP by beta-secretase to release sAPP-beta which is further cleaved to release an N-terminal fragment of APP (N-APP) (PubMed:23559013). N-APP binds TNFRSF21; this triggers caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6) (PubMed:23559013). Negatively regulates oligodendrocyte survival, maturation and myelination (PubMed:21725297). Plays a role in signaling cascades triggered by stimulation of T-cell receptors, in the adaptive immune response and in the regulation of T-cell differentiation and proliferation (By similarity). Negatively regulates T-cell responses and the release of cytokines such as IL4, IL5, IL10, IL13 and IFNG by Th2 cells (By similarity). Negatively regulates the production of IgG, IgM and IgM in response to antigens (By similarity). May inhibit the activation of JNK in response to T-cell stimulation (By similarity). Also acts as a regulator of pyroptosis: recruits CASP8 in response to reactive oxygen species (ROS) and subsequent oxidation, leading to activation of GSDMC (By similarity). http://togogenome.org/gene/10090:Tmbim7 ^@ http://purl.uniprot.org/uniprot/Q9D561|||http://purl.uniprot.org/uniprot/Q9D592 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BI1 family.|||Membrane http://togogenome.org/gene/10090:Slit1 ^@ http://purl.uniprot.org/uniprot/Q80TR4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ During retinal development, is expressed at 12.5 dpc in the dorsocentral region of the retina, and at 17.5 dpc is only very weakly expressed. In the developing optic chiasm is expressed at 12.5 dpc around the junction of the optic nerve and the brain, with strongest expression dorsal to the site at which the optic stalk joins the diencephalon, and also weakly in a subset of the CD44/SSEA neurons. In the more dorsal region of the developing optic chiasm, is expressed in some distance posterior to the axons. However, more ventrally, is expressed in a region directly adjacent to the path taken by the RGC axons. By 17.5 dpc is not longer be detected at the junction of the brain and optic nerve and is only weakly expressed by the CD44/SSEA neurons. Outside the developing brain detected at between 8.5 dpc and 9.5 dpc in the primordiun of the branchial arches, between 9.5 dpc and 10.5 dpc in the posterior dermamyotome. By 11.5 dpc the expression pattern along somite boundaries was most prominent caudally. Weak expression was also observed in the nasal pit at 11.5 dpc. From 13.5 dpc to 17.5 dpc expression was observed in the trigeminal ganglion, in the olfactory epithelium, and in the neural layer of the retina in the developing eye (with strongest expression in the inner nuclear layer).|||Interacts with GREM1 (By similarity) and ROBO1.|||Mice show significant axon guidance errors in a variety of pathways, including corticofugal, callosal and thalamocortical tracts. Mice double-deficient in SLIT1 and SLIT2 show retinal axon guidance defects and a disorganized lateral olfactory tract (LOT).|||Secreted|||Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions (By similarity). SLIT1 and SLIT2 together seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. http://togogenome.org/gene/10090:Impa1 ^@ http://purl.uniprot.org/uniprot/A0A0A6YW07|||http://purl.uniprot.org/uniprot/Q924B0 ^@ Similarity ^@ Belongs to the inositol monophosphatase superfamily. http://togogenome.org/gene/10090:Nos3 ^@ http://purl.uniprot.org/uniprot/P70313|||http://purl.uniprot.org/uniprot/Q8C5P3 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NOS family.|||Binds 1 FAD.|||Binds 1 FMN.|||Cell membrane|||Golgi apparatus|||Homodimer. Interacts with NOSIP and NOSTRIN (By similarity). Interacts with HSP90AB1 (By similarity). Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.|||Phosphorylation by AMPK at Ser-1176 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin, AMPK also phosphorylates Thr-494, resulting in inhibition of activity (By similarity).|||Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.|||Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. May play a significant role in normal and abnormal limb development.|||Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity).|||Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.|||caveola|||cytoskeleton http://togogenome.org/gene/10090:Hipk3 ^@ http://purl.uniprot.org/uniprot/Q9ERH7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated, but autophosphorylation is not required for catalytic activity.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. HIPK subfamily.|||Cytoplasm|||Heart, skeletal muscle, spleen, testis and lung.|||Interacts with UBL1/SUMO-1 (By similarity). Interacts with and stabilizes ligand-bound androgen receptor (AR). Interacts with Nkx1-2. Interacts with FAS and DAXX. Probably part of a complex consisting of HIPK3, FAS and FADD. Binds to NR5A1/SF1, SPEN/MINT and RUNX2.|||May be sumoylated.|||Nucleus|||Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). http://togogenome.org/gene/10090:Six3 ^@ http://purl.uniprot.org/uniprot/Q62233 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SIX/Sine oculis homeobox family.|||Embryos die at birth and lack most head structures anterior to the midbrain, including the eyes and nose (PubMed:12569128). Embryonic SHH and SIX3 double heterozygous mice exhibit a semilobar holoprosencephaly-like phenotype and a dorsoventral patterning defects in telencephalon (PubMed:18694563). Embryonic WNT1 and SIX3 double homozygous mice lack cerebellum and colliculus and have a severely reduced midbrain (PubMed:18094027). Conditional knockout in eye exhibit drastically reduced lens size, cataracts, or absence of the lens (PubMed:17066077). Embryo of SIX3 and HESX1 heterozygous mice exhibit severe growth retardation after weaning, with additional gonadal and thyroid gland defects, resulting in a lethal phenotype (PubMed:18775421).|||Expressed in ependymal cells during the formation of the lateral wall.|||Expressed in the developing retina (at protein level). First expressed at 6.5 dpc of embryo development around the anterior border. At 8.5 dpc, expression is found over the anterior neural plate. At 9.5 dpc, in the diencephalic part of the ventral forebrain, optic vesicles, olfactory placodes and Rathke pouch. In later stages, present in hypothalamus, eyes and pituitary. Expression at around 7.5 dpc to 8 dpc is high in the anterior neural ectoderm. Weaker expression is detected in the prechordal plate. At the 5 somite stage (8.0 dpc), expression is maintained in the anterior neural ectoderm. Around the 8 somite stage (8.0 dpc), expression is already restricted to the ventral forebrain and eye field. At the 12 somite stage (8.5 dpc), expression is maintained in the ventral forebrain (PubMed:18694563). At 9.5 dpc strongly expressed throughout the prospective nasal ectoderm. At 10.5 dpc remains expressed throughout the nasal ectoderm (PubMed:16024294). At 7.5 dpc expression is found in the developing anterior neuroectoderm. At 9.0 dpc expression is found in the region of the presumptive lens ectoderm and developing optic vesicle. At 9.5 dpc expression is found in the lens placode, optic vesicles, and ventral forebrain (PubMed:11458394).|||Interacts with EYA4; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes. Interacts with MTA1 and HDAC2; represses its own transcription. Interacts with MTA1; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter. Interacts with EYA1; promotes EYA1 translocation to the nucleus. Interacts with TLE1 and TLE5 (via Q domain); can act in combination with either TLE1 and/or TLE5 leading to transcriptional repression or activation, respectively (By similarity). Interacts (via homeobox) with NR4A3; differentially regulates the transcriptional activities NR4A3 (By similarity). Interacts with GMNN (By similarity). Interacts with TLE4.|||Nucleus|||Represses its own transcription in a TLE4-dependent manner. Induces in lens by PAX6 in a dosage-dependent manner. Activated by SOX2 during forebrain development. Inhibited by MTA1 in mammary glands.|||Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon (PubMed:18094027). Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression (PubMed:18775421). In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration (PubMed:22071110). Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 AND CCND2 (PubMed:17576749). During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm (PubMed:17066077). In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation (PubMed:12072567). Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory (PubMed:20890044). Its action during retina development and lens morphogenesis is TLE5 and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element (PubMed:11139622). Directly activates RHO transcription, or cooperates with CRX or NRL (PubMed:17666527). Six3 functions also in the formation of the proximodistal axis of the optic cup (PubMed:12163408), and promotes the formation of optic vesicles-like structures (PubMed:11458394). During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (PubMed:18694563). Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway (By similarity). http://togogenome.org/gene/10090:Klhdc7a ^@ http://purl.uniprot.org/uniprot/A2APT9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ptgir ^@ http://purl.uniprot.org/uniprot/P43252 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts (non-isoprenylated C-terminus) with PDZK1.|||Isoprenylation does not influence ligand binding but is required for efficient coupling to the effectors adenylyl cyclase and phospholipase C.|||Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase. http://togogenome.org/gene/10090:Kcnn3 ^@ http://purl.uniprot.org/uniprot/P58391 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the potassium channel KCNN family. KCa2.3/KCNN3 subfamily.|||Expressed at low levels in atrial and ventricular myocytes (at protein level).|||Forms a voltage-independent potassium channel activated by intracellular calcium (PubMed:11557517). Activation is followed by membrane hyperpolarization (By similarity). Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization (By similarity).|||Heterooligomer. The complex is composed of 4 channel subunits each of which binds to a calmodulin subunit which regulates the channel activity through calcium-binding (By similarity). Interacts with CALM1 (By similarity).|||Inhibited by bee venom neurotoxin apamin.|||Membrane http://togogenome.org/gene/10090:Trcg1 ^@ http://purl.uniprot.org/uniprot/Q58Y74 ^@ Tissue Specificity ^@ Expression is restricted to circumvallate papillae. http://togogenome.org/gene/10090:Irf4 ^@ http://purl.uniprot.org/uniprot/Q5SUZ4|||http://purl.uniprot.org/uniprot/Q5SUZ5|||http://purl.uniprot.org/uniprot/Q64287 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IRF family.|||Interacts with SPIB and DEF6 (By similarity). Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct. Directly interacts with NLRP3 in the nucleus of Th2 cells; this interaction enhances IRF4 ability to bind to the IL4 promoter and is required for optimal IRF4-dependent IL4 transcription (PubMed:26098997). Interacts with SPI1 (By similarity).|||Lymphoid cells.|||Not induced by interferons.|||Nucleus|||Phosphorylation by ROCK2 regulates IL-17 and IL-21 production.|||Transcriptional activator. Binds to the interferon-stimulated response element (ISRE) of the MHC class I promoter. Binds the immunoglobulin lambda light chain enhancer, together with PU.1. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 and activation of genes. http://togogenome.org/gene/10090:Mal2 ^@ http://purl.uniprot.org/uniprot/Q2KHK7|||http://purl.uniprot.org/uniprot/Q8BI08 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the MAL family.|||Cell membrane|||Interacts with TPD52L2.|||Member of the machinery of polarized transport. Required for the indirect transcytotic route at the step of the egress of the transcytosing cargo from perinuclear endosomes in order for it to travel to the apical surface via a raft-dependent pathway (By similarity).|||Membrane http://togogenome.org/gene/10090:Or6d15 ^@ http://purl.uniprot.org/uniprot/Q8VF82 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mpped2 ^@ http://purl.uniprot.org/uniprot/B1APT2|||http://purl.uniprot.org/uniprot/Q9CZJ0 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Belongs to the UPF0046 family.|||Displays low metallophosphoesterase activity (in vitro). May play a role in the development of the nervous system.|||Homodimer.|||Inhibited by nmolar levels of AMP and GMP. http://togogenome.org/gene/10090:Tymp ^@ http://purl.uniprot.org/uniprot/Q99N42 ^@ Function|||Similarity|||Subunit ^@ Belongs to the thymidine/pyrimidine-nucleoside phosphorylase family.|||Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (By similarity).|||Homodimer. http://togogenome.org/gene/10090:Hpf1 ^@ http://purl.uniprot.org/uniprot/Q8CFE2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HPF1 family.|||Chromosome|||Cofactor for serine ADP-ribosylation that confers serine specificity on PARP1 and PARP2 and plays a key role in DNA damage response. Initiates the repair of double-strand DNA breaks: recruited to DNA damage sites by PARP1 and PARP2 and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues, licensing serine ADP-ribosylation of target proteins. Serine ADP-ribosylation of target proteins, such as histones, promotes decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. HPF1 acts by completing the active site of PARP1 and PARP2: forms a composite active site composed of residues from HPF1 and PARP1 or PARP2. While HPF1 promotes the initiation of serine ADP-ribosylation, it restricts the polymerase activity of PARP1 and PARP2 in order to limit the length of poly-ADP-ribose chains. HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1.|||Interacts with PARP1 (via the PARP catalytic domain). Interacts with PARP2 (via the PARP catalytic domain). Interacts with core nucleosomes in a PARP1- and PARP2-dependent manner.|||Nucleus http://togogenome.org/gene/10090:Nid1 ^@ http://purl.uniprot.org/uniprot/P10493 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with FBLN1 and LGALS3BP. Interacts with PLXDC1.|||N- and O-glycosylated.|||Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin. Also binds to collagen IV and perlecan. It probably has a role in cell-extracellular matrix interactions.|||basement membrane http://togogenome.org/gene/10090:Sptbn2 ^@ http://purl.uniprot.org/uniprot/Q68FG2 ^@ Similarity ^@ Belongs to the spectrin family. http://togogenome.org/gene/10090:Tceal3 ^@ http://purl.uniprot.org/uniprot/Q8R0A5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TFS-II family. TFA subfamily.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Cnot6 ^@ http://purl.uniprot.org/uniprot/Q8K3P5 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCR4/nocturin family.|||Binds 2 magnesium ions, but the ions interact each with only 1 or 2 residues.|||Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8. Interacts with CNOT7 and CNOT8 (By similarity). Interacts with UNR (PubMed:15314026). Interacts with ZFP36L1 (via N-terminus). Interacts with ZNF335 (By similarity).|||Cytoplasm|||Expressed in embryonic stem (ES) cells.|||Nucleus|||Poly(A) nuclease with 3'-5' RNase activity. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in mRNA decay mediated by the major-protein-coding determinant of instability (mCRD) of the FOS gene in the cytoplasm. In the presence of ZNF335, enhances ligand-dependent transcriptional activity of nuclear hormone receptors. Mediates cell proliferation and cell survival and prevents cellular senescence. http://togogenome.org/gene/10090:Ncdn ^@ http://purl.uniprot.org/uniprot/Q9Z0E0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the neurochondrin family.|||Death between 3.5 and 6.5 dpc. Heterozygous mutant do not display gross anatomic abnormalities. They however show abnormalities in developing cartilage. Nervous system-specific gene disruption by conditional knockout results in epileptic seizure. Displays no overt neurite outgrowth phenotype (PubMed:15790563). Shows a behavioral phenotype associated with a rodent model of schizophrenia, as observed in alterations in both sensorimotor gating and psychotomimetic-induced locomotor activity.|||Endosome membrane|||Expressed in the neuronal, chondral and bone tissues. Expressed in dendrites. Enriched in the brain in the surface layer I-IV. In brains, protein level increases in male but decreases in female with advancing age (at protein level). In adult brains, it is highly expressed in the forebrain and hindbrain. Highly expressed in the hippocampus, piriform cortex, septum, amygdaloid complex, medial geniculate nucleus, inferior colliculus, cerebellar nuclei and the nuclei of the Vth, VIIth, and XIIth cranial nerves. In bone tissues, it is expressed in osteoblasts and osteocytes.|||In the developing brain, it is first expressed in the hindbrain and spinal cord at 10.5 dpc followed by expression in the midbrain at 11.5 dpc. By 18 dpc it is also expressed in the diencephalon and telencephalon, with a strongest expression in the hindbrain. Highly expressed in the developing olfactory bulb and in the lateral choroid plexus.|||Interacts with MCHR1 (By similarity). Interacts with SEMA4C (PubMed:11162505). Interacts with DIAPH1 (via FH3 domain) (PubMed:18572016). Interacts with GRM5 (By similarity).|||Palmitoylated. Palmitoylation by ZDHHC1, ZDHHC3 and ZDHHC11 regulates the association of NCDN with endosome membranes. May also be palmitoylated by ZDHHC7.|||Postsynapse|||Probably involved in signal transduction, in the nervous system, via increasing cell surface localization of GRM5 and positively regulating its signaling. Required for the spatial learning process. Acts as a negative regulator of Ca(2+)-calmodulin-dependent protein kinase 2 (CaMK2) phosphorylation. May play a role in modulating melanin-concentrating hormone-mediated functions via its interaction with MCHR1 that interferes with G protein-coupled signal transduction. May be involved in bone metabolism. May also be involved in neurite outgrowth.|||cytosol|||dendrite http://togogenome.org/gene/10090:Sri ^@ http://purl.uniprot.org/uniprot/Q6P069 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-binding protein that modulates excitation-contraction coupling in the heart. Contributes to calcium homeostasis in the heart sarcoplasmic reticulum. Modulates the activity of RYR2 calcium channels.|||Cytoplasm|||Detected in cardiac myocytes.|||Homodimer. Interacts with GCA, RYR2 and ANXA7 (By similarity).|||Sarcoplasmic reticulum membrane|||This protein has been shown to bind calcium with high affinity. http://togogenome.org/gene/10090:Or8b52 ^@ http://purl.uniprot.org/uniprot/Q7TRC3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cmc4 ^@ http://purl.uniprot.org/uniprot/A3KGA5|||http://purl.uniprot.org/uniprot/Q61908 ^@ Domain|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CMC4 family.|||Expressed in many tissues.|||Mitochondrion|||Shares a non-coding 5' exon with isoform 2 which is spliced to a different set of 3' exons encoding an unrelated protein.|||The twin Cx9C motifs are involved in the recognition by the mitochondrial disulfide relay system. http://togogenome.org/gene/10090:Nkain1 ^@ http://purl.uniprot.org/uniprot/Q9D035 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NKAIN family.|||Cell membrane|||Detected in the brain only and specifically in neurons. Expressed in multiple regions such as cerebral cortex, thalamus, hippocampus, olfactory bulb and brainstem as well as in cerebellum with high expression in granular cell layer.|||Interacts with ATP1B1 C-terminus. http://togogenome.org/gene/10090:Esd ^@ http://purl.uniprot.org/uniprot/H3BKH6|||http://purl.uniprot.org/uniprot/Q9R0P3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the esterase D family.|||Cytoplasm|||Cytoplasmic vesicle|||Homodimer.|||Serine hydrolase involved in the detoxification of formaldehyde. http://togogenome.org/gene/10090:Gm21661 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or52p1 ^@ http://purl.uniprot.org/uniprot/Q8VGX9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Shisa5 ^@ http://purl.uniprot.org/uniprot/Q9D7I0 ^@ Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shisa family.|||Can induce apoptosis in a caspase-dependent manner and plays a role in p53/TP53-dependent apoptosis.|||Endoplasmic reticulum membrane|||Induced in a p53/TP53-dependent manner in response to cellular stress.|||Interacts with PDCD6; PDCD6 can stabilze SHISA5.|||Nucleus membrane|||Probable cloning artifact.|||Spleen and thymus.|||The proline-rich region is required for endoplasmic reticulum localization. http://togogenome.org/gene/10090:Cdk19 ^@ http://purl.uniprot.org/uniprot/G5E8L1|||http://purl.uniprot.org/uniprot/Q8BKC7|||http://purl.uniprot.org/uniprot/Q8BWD8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Cytoplasm|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Nrde2 ^@ http://purl.uniprot.org/uniprot/Q80XC6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NRDE2 family.|||Interacts with MTREX; the interaction is direct and stabilizes NRDE2 (By similarity). Interacts with EXOSC10, EFTUD2 and EIF4A3 (By similarity).|||Nucleus|||Nucleus speckle|||Protein of the nuclear speckles that regulates RNA degradation and export from the nucleus through its interaction with MTREX an essential factor directing various RNAs to exosomal degradation. Changes the conformation of MTREX, precluding its association with the nuclear exosome and interaction with proteins required for its function in RNA exosomal degradation. Negatively regulates, for instance, the degradation of mRNAs and lncRNAs by inhibiting their MTREX-mediated recruitment to nuclear exosome. By preventing the degradation of RNAs in the nucleus, it promotes their export to the cytoplasm (By similarity). U5 snRNP-associated RNA splicing factor which is required for efficient splicing of CEP131 pre-mRNA and plays an important role in centrosome maturation, integrity and function during mitosis (By similarity). Suppresses intron retention in a subset of pre-mRNAs containing short, GC-rich introns with relatively weak 5' and 3' splice sites (By similarity). Plays a role in DNA damage response (By similarity).|||The MID/MTR4-interacting domain is necessary and sufficient to mediate interaction with MTREX.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Cacybp ^@ http://purl.uniprot.org/uniprot/Q9CXW3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in brain and EAT cells. Expressed at low level in heart, muscle, and at very low level in the liver, spleen, lung, kidney and stomach.|||May be involved in calcium-dependent ubiquitination and subsequent proteasomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1) (By similarity).|||Monomer or homodimer. Component of some large E3 complex at least composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts directly with SIAH1, SIAH2 and SKP1 (By similarity). Interacts with proteins of the S100 family S100A1, S100A6, S100B, S100P and S100A12 in a calcium-dependent manner (By similarity).|||Nucleus|||Phosphorylated on serine residues. Phosphorylated upon induction by RA or at high calcium concentrations. http://togogenome.org/gene/10090:Bltp1 ^@ http://purl.uniprot.org/uniprot/A2AAE1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Endoplasmic reticulum membrane|||Expressed during spermatogenesis and adipogenesis.|||Highly expressed in testis and ovary. Weakly or not expressed in other tissues.|||Mitochondrion membrane|||Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum. Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics. Acts as regulator of phagocytosis. http://togogenome.org/gene/10090:Fkbp6 ^@ http://purl.uniprot.org/uniprot/Q91XW8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it contains a PPIase FKBP-type domain, does not show peptidyl-prolyl cis-trans isomerase activity.|||Belongs to the FKBP6 family.|||Chromosome|||Co-chaperone required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes.|||Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH; leading to inhibit GAPDH catalytic activity (By similarity). Interacts (via TPR repeats) with HSP90.|||Males mice are sterile and aspermic due to abnormal pachytene spermatocytes, characterized by the appearance of unusual inclusion bodies and dense compacted nuclei. Spermatocytes fail to proceed beyond the pachytene stage due to abnormal pairing and misalignments between homologous chromosomes, non-homologous partner switches and autosynapsis of X chromosome cores in meiotic spermatocytes. No other abnormalities are detected in any tissues of males. Females mice are fertile (PubMed:12764197). Spermatocytes show derepressed LINE-1 retrotransposon and reduced DNA methylation due to deficient nuclear accumulation of Miwi2 (PubMed:22902560).|||Nucleus|||Present in spermatocytes. Expression is lost as cells exit prophase I. Not detected in spermatids (at protein level).|||Testis-specific.|||cytosol http://togogenome.org/gene/10090:Pex19 ^@ http://purl.uniprot.org/uniprot/Q8VCI5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxin-19 family.|||Cytoplasm|||Interacts with a broad range of peroxisomal membrane proteins, including PEX3, PEX10, PEX11A, PEX11B, PEX12, PEX13, PEX14 and PEX16, PXMP2/PMP22, PXMP4/PMP24, SLC25A17/PMP34, ABCD1/ALDP, ABCD2/ALDRP, and ABCD3/PMP70. Also interacts with the tumor suppressor CDKN2A/p19ARF (By similarity).|||Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.|||Peroxisome membrane http://togogenome.org/gene/10090:Rspo1 ^@ http://purl.uniprot.org/uniprot/B1ASC1|||http://purl.uniprot.org/uniprot/Q9Z132 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes (PubMed:21693646). Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination (By similarity). Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 (By similarity).|||Belongs to the R-spondin family.|||Expressed in the dorsal part of the neural tube on 10 and 12 dpc, especially in the boundary region between roof plate and neuroepithelium. This expression is enhanced in the rostral part. Also expressed in other tissues such as truncal region neighboring forelimbs and mesenchymal tissues around the nasal cavity.|||Interacts with ZNRF3; promoting indirect interaction between ZNRF3 and LGR4 and membrane clearance of ZNRF3. Identified in a complex composed of RNF43, LGR5 and RSPO1 (By similarity). Interacts with the extracellular domain of FZD8 and LRP6. It however does not form a ternary complex with FZD8 and LRP6. Interacts with WNT1. Binds heparin. Interacts with LGR4, LGR5 and LGR6 (PubMed:16543246, PubMed:21693646). Interacts (via FU repeats) with KREM1 (By similarity).|||Nucleus|||Secreted|||The FU repeats are required for activation and stabilization of beta-catenin.|||Transiently expressed in the central nervous system (CNS) during development. Predominantly expressed in the tailbud of embryos. Also detected in the primitive streak, dorsal neural tube, forebrain and migrating neural crests of embryos. Detected from day 9.5, in various neural and mesodermal derivatives, mainly along dorsal neural tube and diencephalon. Strongly expressed in limb buds, particularly in the morphogenetically active region such as the apical ectodermal ridge (AER). The developing skin showed expression in patches of the developing dermis at 12.5 dpc and at lower levels at 14.5 dpc. By 18.5 dpc expression is restricted to the dermal papilla of the developing hair, which persisted into adulthood. In the developing kidney, strong expression at 11.5 dpc in the uninduced metanephric mesenchyme is observed. By 14.5 dpc this expression is restricted to the condensing mesenchyme surrounding the ureter and the developing nephrons. Specific expression in the urogenital ridge as early as 10.5 dpc in the coelomic epithelium. Sex-specific differences of expression began to appear starting at 12.5 dpc, with an increase in the somatic cells of the XX gonad. http://togogenome.org/gene/10090:Art1 ^@ http://purl.uniprot.org/uniprot/Q545U9|||http://purl.uniprot.org/uniprot/Q60935 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in cardiac and skeletal muscle. Low levels also found in lung.|||Belongs to the Arg-specific ADP-ribosyltransferase family.|||Has ADP-ribosyltransferase activity toward GLP1R.|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Myo5a ^@ http://purl.uniprot.org/uniprot/D3YZ62|||http://purl.uniprot.org/uniprot/D3Z4J3|||http://purl.uniprot.org/uniprot/Q99104 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Detected in melanocytes.|||May be a homodimer, which associates with multiple calmodulin or myosin light chains (PubMed:17151196). Interacts with RIPL2, the interaction is required for its role in dendrite formation (PubMed:23798443). Interacts with MLPH (PubMed:11887186). Interacts with SYTL4 (PubMed:23798443). Interacts with MYRIP (PubMed:12221080). Interacts with RAB10; mediates the transport to the plasma membrane of SLC2A4/GLUT4 storage vesicles (PubMed:22908308). Interacts with FMR1; this interaction occurs in association with polyribosome (PubMed:12147688).|||Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Involved in melanosome transport. Also mediates the transport of vesicles to the plasma membrane. May also be required for some polarization process involved in dendrite formation. http://togogenome.org/gene/10090:Agfg1 ^@ http://purl.uniprot.org/uniprot/Q8K2K6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contains FG repeats.|||Cytoplasmic vesicle|||Expressed in the testes (at protein level).|||Highly expressed during spermiogenesis.|||Interacts with FCHO1 (By similarity). Interacts with EPS15R and EPS15.|||Mice have a normal life-span and show no apparent abnormalities. Females display normal fertility but males are infertile due to a lack of acrosome in their spermatozoa.|||Nucleus|||O-glycosylated.|||Required for vesicle docking or fusion during acrosome biogenesis. May play a role in RNA trafficking or localization. http://togogenome.org/gene/10090:Mdfi ^@ http://purl.uniprot.org/uniprot/P70331 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MDFI family.|||Cytoplasm|||In the embryo, highly expressed in the sclerotome. Also expressed in the notochord, neural tube, limb buds, heart, branchial arches and head mesenchyme. In the adult, highly expressed in skeletal muscle. Expressed at lower levels in most other tissues.|||Inhibits the transactivation activity of the Myod family of myogenic factors and represses myogenesis. Acts by associating with Myod family members and retaining them in the cytoplasm by masking their nuclear localization signals. Can also interfere with the DNA-binding activity of Myod family members. Plays an important role in trophoblast and chondrogenic differentiation. Regulates the transcriptional activity of TCF7L1/TCF3 by interacting directly with TCF7L1/TCF3 and preventing it from binding DNA. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin regulation of the WNT and JNK signaling pathways.|||Nucleus|||The C-terminus interacts with AXIN1 and LEF1 (PubMed:12192039). Interacts with CCNT2 (By similarity). http://togogenome.org/gene/10090:Prss40 ^@ http://purl.uniprot.org/uniprot/A6H6T1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Expressed in testis. More specifically, abundantly expressed in the haploid round spermatid.|||May play an important role in the sperm/egg interaction; released during the acrosome reaction.|||Secreted|||There appears to be no human ortholog of this protein.|||acrosome http://togogenome.org/gene/10090:Hsf1 ^@ http://purl.uniprot.org/uniprot/A0A075F5C6|||http://purl.uniprot.org/uniprot/A0A075F6C2|||http://purl.uniprot.org/uniprot/A0A075F882|||http://purl.uniprot.org/uniprot/A0A075F891|||http://purl.uniprot.org/uniprot/P38532|||http://purl.uniprot.org/uniprot/Q52L52 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated on Lys-118; this acetylation is decreased in a IER5-dependent manner. Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner. Acetylated on Lys-80; this acetylation inhibits DNA-binding activity upon heat shock. Deacetylated on Lys-80 by SIRT1; this deacetylation increases DNA-binding activity.|||Belongs to the HSF family.|||Cytoplasm|||Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival. Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 (By similarity). Binds the promoter region upstream of exon 1 of Mpv17l to activate expression of the M-LPS isoform which is involved in metabolism of reactive oxygen species (PubMed:20231359). Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner. Plays a role in nuclear export of stress-induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner.|||In unstressed cells, spontaneous homotrimerization is inhibited. Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation. Furthermore, intramolecular interactions between the regulatory domain and the nonadjacent transactivation domain prevents transcriptional activation, a process that is relieved upon heat shock. The regulatory domain is necessary for full repression of the transcriptional activation domain in unstressed cells through its phosphorylation on Ser-303 and Ser-307. In heat stressed cells, HSF1 homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity. The D domain is necessary for translocation to the nucleus, interaction with JNK1 and MAPK3 and efficient JNK1- and MAPK3-dependent phosphorylation. The regulatory domain confers heat shock inducibility on the transcriptional transactivation domain. The regulatory domain is necessary for transcriptional activation through its phosphorylation on Ser-230 upon heat shock. 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors.|||Monomer; cytoplasmic latent and transcriptionally inactive monomeric form in unstressed cells. Homotrimer; in response to stress, such as heat shock, homotrimerizes and translocates into the nucleus, binds to heat shock element (HSE) sequences in promoter of heat shock protein (HSP) genes and acquires transcriptional ability. Interacts (via monomeric form) with FKBP4; this interaction occurs in unstressed cells. Associates (via monomeric form) with HSP90 proteins in a multichaperone complex in unnstressed cell; this association maintains HSF1 in a non-DNA-binding and transcriptional inactive form by preventing HSF1 homotrimerization. Homotrimeric transactivation activity is modulated by protein-protein interactions and post-translational modifications. Interacts with HSP90AA1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities. Part (via regulatory domain in the homotrimeric form) of a large heat shock-induced HSP90-dependent multichaperone complex at least composed of FKBP4, FKBP5, HSP90 proteins, PPID, PPP5C and PTGES3; this association maintains the HSF1 homotrimeric DNA-bound form in a transcriptionally inactive form. Interacts with BAG3 (via BAG domain); this interaction occurs in normal and heat-shocked cells promoting nuclear shuttling of HSF1 in a BAG3-dependent manner. Interacts (via homotrimeric and hyperphosphorylated form) with FKBP4; this interaction occurs upon heat shock in a HSP90-dependent multichaperone complex. Interacts (via homotrimeric form preferentially) with EEF1A proteins. In heat shocked cells, stress-denatured proteins compete with HSF1 homotrimeric DNA-bound form for association of the HSP90-dependent multichaperone complex, and hence alleviating repression of HSF1-mediated transcriptional activity. Interacts (via homotrimeric form preferentially) with DAXX; this interaction relieves homotrimeric HSF1 from repression of its transcriptional activity by HSP90-dependent multichaperone complex upon heat shock. Interacts (via D domain and preferentially with hyperphosphorylated form) with JNK1; this interaction occurs under both normal growth conditions and immediately upon heat shock. Interacts (via D domain and preferentially with hyperphosphorylated form) with MAPK3; this interaction occurs upon heat shock. Interacts with IER5 (via central region); this interaction promotes PPP2CA-induced dephosphorylation on Ser-121, Ser-307, Ser-314 and Thr-323 and HSF1 transactivation activity. Found in a ribonucleoprotein complex composed of the HSF1 homotrimeric form, translation elongation factor eEF1A proteins and non-coding RNA heat shock RNA-1 (HSR1); this complex occurs upon heat shock and stimulates HSF1 DNA-binding activity. Interacts (via transactivation domain) with HSPA1A/HSP70 and DNAJB1; these interactions result in the inhibition of heat shock- and HSF1-induced transcriptional activity during the attenuation and recovery phase from heat shock. Interacts (via Ser-303 and Ser-307 phosphorylated form) with YWHAE; this interaction promotes HSF1 sequestration in the cytoplasm in an ERK-dependent manner. Found in a complex with IER5 and PPP2CA. Interacts with TPR; this interaction increases upon heat shock and stimulates export of HSP70 mRNA. Interacts with SYMPK (via N-terminus) and CSTF2; these interactions occur upon heat shock. Interacts (via transactivation domain) with HSPA8. Interacts with EEF1D; this interaction occurs at heat shock promoter element (HSE) sequences. Interacts with MAPKAPK2. Interacts with PRKACA/PKA. Interacts (via transactivation domain) with GTF2A2. Interacts (via transactivation domain) with GTF2B. Interacts (via transactivation domain) with TBP. Interacts with CDK9, CCNT1 and EP300. Interacts (via N-terminus) with XRCC5 (via N-terminus) and XRCC6 (via N-terminus); these interactions are direct and prevent XRCC5/XRCC6 heterodimeric binding and non-homologous end joining (NHEJ) repair activities induced by ionizing radiation (IR). Interacts with PLK1; this interaction occurs during the early mitotic period, increases upon heat shock but does not modulate neither HSF1 homotrimerization and DNA-binding activities. Interacts (via Ser-216 phosphorylated form) with CDC20; this interaction occurs in mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated degradation of HSF1 by blocking the recruitment of the SCF(BTRC) ubiquitin ligase complex. Interacts with MAD2L1; this interaction occurs in mitosis. Interacts with BTRC; this interaction occurs during mitosis, induces its ubiquitin-dependent degradation following stimulus-dependent phosphorylation at Ser-216, a process inhibited by CDC20. Interacts with HSP90AA1 and HSP90AB1. Forms a complex with TTC5/STRAP and p300/EP300; these interactions augment chromatin-bound HSF1 and p300/EP300 histone acetyltransferase activity (By similarity).|||Nucleus|||Phosphorylated. Phosphorylated in unstressed cells; this phosphorylation is constitutive and implicated in the repression of HSF1 transcriptional activity. Phosphorylated on Ser-121 by MAPKAPK2; this phosphorylation promotes interaction with HSP90 proteins and inhibits HSF1 homotrimerization, DNA-binding and transactivation activities. Phosphorylation on Ser-303 by GSK3B/GSK3-beat and on Ser-307 by MAPK3 within the regulatory domain is involved in the repression of HSF1 transcriptional activity and occurs in a RAF1-dependent manner. Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner. Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303. According to, Ser-303 is not phosphorylated in unstressed cells. Phosphorylated on Ser-415 by PLK1; phosphorylation promotes nuclear translocation upon heat shock. Hyperphosphorylated upon heat shock and during the attenuation and recovery phase period of the heat shock response. Phosphorylated on Thr-142; this phosphorylation increases HSF1 transactivation activity upon heat shock. Phosphorylation on Ser-230 by CAMK2A; this phosphorylation enhances HSF1 transactivation activity upon heat shock. Phosphorylation on Ser-326 by MAPK12; this phosphorylation enhances HSF1 nuclear translocation, homotrimerization and transactivation activities upon heat shock. Phosphorylated on Ser-320 by PRKACA/PKA; this phosphorylation promotes nuclear localization and transcriptional activity upon heat shock. Phosphorylated by MAPK8; this phosphorylation occurs upon heat shock, induces HSF1 translocation into nuclear stress bodies and negatively regulates transactivation activity. Neither basal nor stress-inducible phosphorylation on Ser-230, Ser-292, Ser-303, Ser-307, Ser-314, Ser-319, Ser-320, Thr-323, Ser-326, Ser-338, Ser-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity. Phosphorylated on Ser-216 by PLK1 in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex inducing HSF1 degradation, and hence mitotic progression. Dephosphorylated on Ser-121, Ser-307, Ser-314 and Thr-323 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity.|||Sumoylated with SUMO1 and SUMO2 upon heat shock in a ERK2-dependent manner. Sumoylated by SUMO1 on Lys-298; sumoylation occurs upon heat shock and promotes its localization to nuclear stress bodies and DNA-binding activity. Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.|||Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis. Polyubiquitinated. Undergoes proteasomal degradation upon heat shock and during the attenuation and recovery phase period of the heat shock response.|||centrosome|||kinetochore|||nucleoplasm|||perinuclear region|||spindle pole http://togogenome.org/gene/10090:Slc25a34 ^@ http://purl.uniprot.org/uniprot/A2ADF7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrion inner membrane|||Putative antiporter that exchanges dicarboxylates and sulfur oxoanions across the inner membrane of mitochondria. http://togogenome.org/gene/10090:Prkn ^@ http://purl.uniprot.org/uniprot/A0A3B2W489|||http://purl.uniprot.org/uniprot/Q9WVS6 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinates in an E2-dependent manner leading to its own degradation. Also polyubiquitinated by RNF41 for proteasomal degradation.|||Belongs to the RBR family. Parkin subfamily.|||Endoplasmic reticulum|||Expressed in all subdivisions of the brain (at protein level) (PubMed:11675120). Highly expressed in brainstem, cranial nerve, pontine, cerebellar nuclei, indusium griseum, nuclei reticularis, strata oriens and laccunosum moleculare of the hippocampal CA2 region (PubMed:11122330). Low levels were found in the telencephalon and diencephalon (PubMed:11122330). Expressed in heart, liver, skeletal muscle, kidney and testis (PubMed:10818204).|||Forms an E3 ubiquitin ligase complex with UBE2L3 or UBE2L6. Mediates 'Lys-63'-linked polyubiquitination by associating with UBE2V1. Part of a SCF-like complex, consisting of PRKN, CUL1 and FBXW7. Interacts with SNCAIP. Binds to the C2A and C2B domains of SYT11. Interacts and regulates the turnover of SEPTIN5. Part of a complex, including STUB1, HSP70 and GPR37. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN and GPR37, thus facilitating PRKN-mediated GPR37 ubiquitination. HSP70 transiently associates with unfolded GPR37 and inhibits the E3 activity of PRKN, whereas, STUB1 enhances the E3 activity of PRKN through promotion of dissociation of HSP70 from PRKN-GPR37 complexes. Interacts with PSMD4 and PACRG. Interacts with LRRK2. Interacts with RANBP2. Interacts with SUMO1 but not SUMO2, which promotes nuclear localization and autoubiquitination. Interacts (via first RING-type domain) with AIMP2 (via N-terminus). Interacts with PSMA7 and RNF41. Interacts with PINK1. Forms a complex with PINK1 and PARK7. Interacts with CHPF, the interaction with isoform 2 may facilitate PRKN transport into the mitochondria. Interacts with MFN2 (phosphorylated), promotes PRKN localization in dysfunctional depolarized mitochondria. Interacts with FBXO7; this promotes translocation to dysfunctional depolarized mitochondria. Interacts with ZNF746. Interacts with heat shock protein 70 family members, including HSPA1L, HSPA1A and HSPA8; interaction HSPA1L promotes translocation to damaged mitochondria. Interacts with BAG4 and, to a lesser extent, BAG5; interaction with BAG4 inhibits translocation to damaged mitochondria. Forms a complex with PRKN and PARK7 (By similarity). Interacts with AMBRA1 (PubMed:21753002).|||Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:32047033, PubMed:29311685). Substrates include SYT11 and VDAC1 (PubMed:32047033, PubMed:29311685). Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2 (By similarity). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:32047033, PubMed:25474007). Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (By similarity). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (By similarity). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (By similarity). Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:32047033, PubMed:25474007, PubMed:22082830, PubMed:24898855). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:32047033, PubMed:22082830, PubMed:24898855). Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin (PubMed:25474007). After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30 (PubMed:21753002). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy (By similarity). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:24192653). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity). Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (By similarity). Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A (By similarity). Limits the production of reactive oxygen species (ROS) (By similarity). Regulates cyclin-E during neuronal apoptosis (By similarity). In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (By similarity). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene (By similarity).|||In brain, increased protein levels of p53/TP53 and CHPF (PubMed:19801972, PubMed:22082830). Cortical neurons display a slight increase in process fragmentation but no dendritic retraction (PubMed:24898855).|||In late 10 dpc weakly expressed in postmitotic neurons in the mantle layer of the developing nervous system (at protein level). Expression increased at 11-12 dpc (at protein level). At 15-16 dpc, as more specialized neurons and nonneural cells are formed, expression is more tissue specific (at protein level). Expression was highest in the neurites, moderate levels were observed in the migrating postmitotic neurons in the intermediate and neopallial layers (at protein level). In the diencephalon and other CNS regions, while the weakest level of expression was observed in the cell bodies (at protein level). In nonneural tissues, high levels of expression were found in the muscle walls of the intestine, the blood vessels and the dermis (at protein level).|||In the autoinhibited state the side chain of Phe-462 inserts into a hydrophobic groove in RING-0, occluding the ubiquitin acceptor site Cys-430, whereas the REP repressor element binds RING-1 and blocks its E2-binding site. Activation of PRKN requires 2 steps: (1) phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated ubiquitin, leading to unlock repression of the catalytic Cys-430 by the RING-0 region via an allosteric mechanism and converting PRKN to its fully-active form. According to another report, phosphorylation at Ser-65 by PINK1 is not essential for activation and only binding to phosphorylated ubiquitin is essential to unlock repression. In addition, ISG15 conjugation positively regulates its ubiquitin E3 ligase activity by suppressing the intramolecular interaction that maintains its autoinhibited conformation.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.|||Mitochondrion|||Mitochondrion outer membrane|||Nucleus|||Phosphorylated. Activation requires phosphorylation at Ser-65 by PINK1 and binding to PINK1 phosphorylated ubiquitin. Phosphorylation at Thr-174 by PINK1 and at Thr-216 is important for mitochondrial localization.|||Postsynaptic density|||Presynapse|||S-nitrosylated.|||The RING-type 1 zinc finger domain is required to repress p53/TP53 transcription.|||The ubiquitin-like domain binds the PSMD4 subunit of 26S proteasomes.|||cytosol|||neuron projection http://togogenome.org/gene/10090:Purb ^@ http://purl.uniprot.org/uniprot/O35295 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PUR DNA-binding protein family.|||Has capacity to bind repeated elements in single-stranded DNA such as the purine-rich single strand of the PUR element located upstream of the MYC gene. Participates in transcriptional and translational regulation of alpha-MHC expression in cardiac myocytes by binding to the purine-rich negative regulatory (PNR) element. Modulates constitutive liver galectin-3 gene transcription by binding to its promoter. May play a role in the dendritic transport of a subset of mRNAs (By similarity). Plays a role in the control of vascular smooth muscle (VSM) alpha-actin gene transcription as repressor in myoblasts and fibroblasts.|||Homodimer, heterodimer with PURA and heterotrimer with PURA and YBX1/Y-box protein 1.|||Nucleus http://togogenome.org/gene/10090:Tatdn2 ^@ http://purl.uniprot.org/uniprot/B7ZNL9|||http://purl.uniprot.org/uniprot/F8VQE6 ^@ Similarity ^@ Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family. http://togogenome.org/gene/10090:Dnajb13 ^@ http://purl.uniprot.org/uniprot/Q80Y75 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed during spermiogenesis.|||Expressed in ciliated cell-containing tissues such as testis, brain, lung, ovary and oviduct.|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.|||Homodimer (By similarity). Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB (PubMed:36417862). Interacts with SUN5 (PubMed:29298896). Interacts with IQUB (PubMed:36417862).|||cilium|||flagellum http://togogenome.org/gene/10090:Kdm3a ^@ http://purl.uniprot.org/uniprot/Q6PCM1 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the JHDM2 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||By beta-adrenergic stimulation (at protein level).|||Cytoplasm|||Expression increases significantly during spermatogenesis with a 70-fold increase from day 7 testis to day 30 testis. First detected in the late pachytene stage, increases in diplotene and secondary spermatocytes and reaches its highest levels in round spermatids.|||Highly expressed in testis (at protein level). Also expressed at high levels in tissues responsive to sympathetic nerve activity such as brown adipose tissue and skeletal muscle.|||Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation (By similarity). Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin (PubMed:17943087). Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1.|||Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.|||Nucleus|||Spermatogenesis defects and adult obesity.|||The JmjC domain and the C6-type zinc-finger are required for the demethylation activity. http://togogenome.org/gene/10090:Abcd3 ^@ http://purl.uniprot.org/uniprot/P55096 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Animals show normal activity and have no obvious malformations. However, necroscopy show increased liver size compared to controls, and fibroblasts show reduced numbers of enlarged peroxisomes. They show however a defect in bile acid biosynthesis and they have impaired beta-oxidation of the branched-chain pristanic and phytanic fatty acids on a phytol-loaded diet.|||Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.|||Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that catalyzes the transport of long-chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched-chain fatty acids-CoA and bile acids from the cytosol to the peroxisome lumen for beta-oxydation. Has fatty acyl-CoA thioesterase and ATPase activities (By similarity). Probably hydrolyzes fatty acyl-CoAs into free fatty acids prior to their ATP-dependent transport into peroxisomes (By similarity). Thus, play a role in regulation of LCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation (PubMed:25168382).|||Homodimers. Can form heterodimers with ABCD1 and ABCD2. Dimerization is necessary to form an active transporter. Interacts with PEX19; mediates the targeting of ABCD3 to peroxisomes.|||Peroxisome membrane|||Ubiquitinated by PEX2 during pexophagy in response to starvation, leading to its degradation. http://togogenome.org/gene/10090:Ccdc107 ^@ http://purl.uniprot.org/uniprot/Q9DCC3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ckap5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0K2|||http://purl.uniprot.org/uniprot/A2AGT5|||http://purl.uniprot.org/uniprot/K3W4R5 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TOG/XMAP215 family.|||Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with TACC1. Interacts with HNRNPA2B1. Interacts with TACC3 independently of clathrin. Interacts with TACC3 and clathrin forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges. Interacts with NDC80; indicative for an association with the NDC80 complex. Interacts with SLAIN2 (By similarity). Interacts with SLAIN1 (PubMed:21646404).|||The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice.|||centrosome|||kinetochore|||spindle|||spindle pole http://togogenome.org/gene/10090:Pspc1 ^@ http://purl.uniprot.org/uniprot/Q8R326 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PSPC family.|||Cytoplasm|||Forms heterodimers with NONO; this involves formation of a coiled coil domain by helices from both proteins (By similarity). Interaction with NONO is required for its targeting to paraspeckles and perinucleolar caps (By similarity). Found in a RNP complex with CAT2 transcribed nuclear RNA (CTN-RNA). Interacts with NONO and SFPQ. Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA.|||Isoform 1 is strongly expressed in testis (leptoten spermatocytes, round spematids and Sertoli cells) and moderately in cerebrum, cerebellum, lung, spleen and ovary (at protein level). Isoform 2 is strongly expressed in kidney and moderately in salivary gland (at protein level).|||Nucleus matrix|||Nucleus speckle|||Together with NONO, required for the formation of nuclear paraspeckles. Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line. Binds to poly(A), poly(G) and poly(U) RNA homopolymers. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.|||nucleolus http://togogenome.org/gene/10090:Bckdha ^@ http://purl.uniprot.org/uniprot/Q3U3J1 ^@ Function|||Similarity ^@ Belongs to the BCKDHA family.|||Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction. http://togogenome.org/gene/10090:U2af2 ^@ http://purl.uniprot.org/uniprot/P26369|||http://purl.uniprot.org/uniprot/Q80XR5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Interacts with U2AF1L4 (PubMed:16819553). Heterodimer with U2AF1. Binds unphosphorylated SF1. Interacts with SCAF11 and SNW1. Interacts with ZRSR2/U2AF1-RS2. Interacts with RBM17. Interacts with PRPF19; the interaction is direct. Interacts with POLR2A (via the C-terminal domain); Interacts with PRPF19; the interaction is direct. Interacts with POLR2A (via the C-terminal domain); recruits PRPF19 and the Prp19 complex to the pre-mRNA. Interacts with KHDC4 (Isoform 2). Interacts with ZRSR2. Interacts with the SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A (By similarity). Interacts (via N-terminus) with CPSF7 (via C-terminus); this interaction stimulates pre-mRNA 3'-end processing by promoting the recruitment of the CFIm complex to cleavage and polyadenylation signals (By similarity).|||Lysyl-hydroxylation at Lys-15 and Lys-276 affects the mRNA splicing activity of the protein, leading to regulate some, but not all, alternative splicing events.|||Necessary for the splicing of pre-mRNA.|||Nucleus|||Plays a role in pre-mRNA splicing and 3'-end processing. By recruiting PRPF19 and the PRP19C/Prp19 complex/NTC/Nineteen complex to the RNA polymerase II C-terminal domain (CTD), and thereby pre-mRNA, may couple transcription to splicing. Required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene. Positively regulates pre-mRNA 3'-end processing by recruiting the CFIm complex to cleavage and polyadenylation signals. http://togogenome.org/gene/10090:Atg9a ^@ http://purl.uniprot.org/uniprot/Q68FE2 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATG9 family.|||Endoplasmic reticulum membrane|||Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer. Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9A-containing vesicles, thereby enabling growth into autophagosomes.|||Homotrimer; forms a homotrimer with a central pore that forms a path between the two membrane leaflets (By similarity). Interacts (via cytoplasmic its C-terminus) with ATG2A (By similarity). Interacts with SUPT20H (By similarity). Interacts (via the tyrosine-based sorting signal motif) with AP4M1; promoting association with the AP-4 complex (By similarity). Interacts with ARFIP1 and ARFIP2 (By similarity). Interacts with ATG4A; the interaction is direct and promotes ATG9A trafficking (By similarity).|||Late endosome membrane|||Lethality; mice die within one day after birth caused by impaired autophagy (PubMed:19926846). Mice also show aberrant activation of the innate immune response (PubMed:19926846). Fetal mice display significantly retarded growth (PubMed:26370455). Conditional deletion in brain causes axon-specific degeneration: mice were born normally, but half of them die within one week, and none live beyond 4 weeks of age (PubMed:28513333). Defects are caused by impaired autophagy in neurons, leading to progressive degeneration in the axons and their terminals, but not in neuronal cell bodies (PubMed:28513333). In addition to defects in autophagy, mice also display impaired necrotic cell death during bone morphogenesis: the bone surface is rougher and bones are more porous due to defects in necrotic cell death in bone surface formation (PubMed:27811852).|||Mitochondrion membrane|||Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:23402761, PubMed:27587839). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome (By similarity). Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion (By similarity). Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1 (By similarity). In addition to autophagy, also plays a role in necrotic cell death (PubMed:27811852).|||Preautophagosomal structure membrane|||Recycling endosome membrane|||The tyrosine-based sorting signal motif, also named YXX-psi motif, promotes interaction with the AP-4 complex.|||autophagosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Nabp2 ^@ http://purl.uniprot.org/uniprot/Q8R2Y9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SOSS-B family. SOSS-B1 subfamily.|||Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways (By similarity).|||Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1. Directly interacts with ATM, SOSS-A/INTS3 and RAD51. Interacts with INTS7 (By similarity).|||Nucleus|||Phosphorylated by ATM in response to DNA damage. Phosphorylation prevents degradation by the proteasome, hence stabilization of the protein and accumulation within cells (By similarity).|||Ubiquitinated in a FBXL5-dependent manner, leading to proteasomal degradation. http://togogenome.org/gene/10090:Fabp1 ^@ http://purl.uniprot.org/uniprot/P12710|||http://purl.uniprot.org/uniprot/Q3V2F7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.|||Binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm. May be involved in intracellular lipid transport.|||Cytoplasm|||Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.|||Plays a role in lipoprotein-mediated cholesterol uptake in hepatocytes. Binds cholesterol. Binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm. May be involved in intracellular lipid transport. http://togogenome.org/gene/10090:Vmn1r71 ^@ http://purl.uniprot.org/uniprot/Q8VIC0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cuedc2 ^@ http://purl.uniprot.org/uniprot/A0A494BAT2|||http://purl.uniprot.org/uniprot/A0A494BB93|||http://purl.uniprot.org/uniprot/Q9CVB0|||http://purl.uniprot.org/uniprot/Q9CXX9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CUEDC2 family.|||Controls PGR and ESR1 protein levels through their targeting for ubiquitination and subsequent proteasomal degradation.|||Cytoplasm|||Interacts with PGR and ESR1.|||Nucleus|||The CUE domain mediates interaction with PGR and ESR1. http://togogenome.org/gene/10090:Hs3st6 ^@ http://purl.uniprot.org/uniprot/A2RTI7|||http://purl.uniprot.org/uniprot/Q3UIC7|||http://purl.uniprot.org/uniprot/Q5GFD5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Expressed in liver and kidney, followed by heart, brain, lung and testis.|||Golgi apparatus membrane|||Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to heparan sulfate. Unlike 3-OST-1, does not convert non-anticoagulant heparan sulfate to anticoagulant heparan sulfate. http://togogenome.org/gene/10090:Vmn1r11 ^@ http://purl.uniprot.org/uniprot/Q3SXA2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Birc6 ^@ http://purl.uniprot.org/uniprot/O88738 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its targets include CASP9 and DIABLO/SMAC. Acts as an inhibitor of CASP3, CASP7 and CASP9. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification. Required for normal placenta development.|||Endosome|||Homodimer. Binds the activated, processed forms of CASP3, CASP6 and CASP7. Interacts with RNF41, KIF23/MKLP1, USP8/UBPY, BIRC5/survivin, MAP2K1/MEK1, RAB8A/RAB8, RAB11A/RAB11, PLK1, EXOC3/SEC6 and EXOC4/SEC8 (By similarity). Interacts with CASP9, DIABLO/SMAC and HTRA2.|||In the C-terminal section; belongs to the ubiquitin-conjugating enzyme family.|||Inhibited by DIABLO/SMAC, HTRA2, CASP3, CASP6, CASP7 and CASP9.|||Mice exhibit perinatal lethality and growth deficiencies, which are linked to a defect in proper placental development.|||Midbody ring|||The BIR domain is essential for its antiapoptotic function and is important for binding to DIABLO/SMAC and CASP9.|||Ubiquitinated. Ubiquitination is mediated by the RNF41 E3 ligase and leads to proteasomal degradation, impairing inhibition of apoptosis. Deubiquitinated by USP8/UBPY (By similarity).|||Widely expressed. Highly expressed in the brain and kidney.|||centrosome|||spindle pole|||trans-Golgi network membrane http://togogenome.org/gene/10090:Ugcg ^@ http://purl.uniprot.org/uniprot/O88693 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 2 family.|||Embryonic lethal (PubMed:10430909). Homozygous knockout embryos initiate gastrulation with clear differentiation into embryonic germ layers, mesoderm, endoderm and ectoderm as well as the regional expression of critical genes (PubMed:10430909). However, a major apoptotic process leads to their resorption that starts at 7.5 dpc and is completed at 9.5 dpc (PubMed:10430909). Neural cell-specific conditional knockout does not affect early brain development but mice die between postnatal days 11 and 24 (PubMed:16109770). Dysfunction of cerebellum and peripheral nerves associated with some structural defects are observed (PubMed:16109770, PubMed:20544855). Peripheral nerves display increased surface area for both axon and myelin (PubMed:16109770). Purkinje cells undergo axonal degeneration associated with a disruption of myelin sheaths (PubMed:20544855). Forebrain neuron-specific conditional knockout leads to development of progressive obesity, hyperleptinemia, and glucose intolerance (PubMed:23554574). Epidermal-specific conditional knockout leads to a significant decrease of the total glucosylceramide content in the epidermis, a failure of the skin water barrier and a detachment of the stratum corneum (PubMed:17145749). Enterocyte-specific conditional knockout mice display deficient absorption of nutritional lipids (PubMed:22851168). Severe defects in intestinal epithelial differentiation also appear between postnatal days 5 and 7 but not before (PubMed:22851168). Hepatocyte-specific conditional knockout does not change basic liver functions with respect to sterol, glucose, and lipoprotein homeostasis (PubMed:20432257).|||Expressed early in preimplantation development, being already detected in eight-cell-stage embryos.|||Golgi apparatus membrane|||Interacts with RTN1; regulates the ceramide glucosyltransferase activity of UGCG.|||Participates in the initial step of the glucosylceramide-based glycosphingolipid/GSL synthetic pathway at the cytosolic surface of the Golgi. Catalyzes the transfer of glucose from UDP-glucose to ceramide to produce glucosylceramide/GlcCer (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) (PubMed:10430909, PubMed:16109770, PubMed:28373486). Glucosylceramide is the core component of glycosphingolipids/GSLs, amphipathic molecules consisting of a ceramide lipid moiety embedded in the outer leaflet of the membrane, linked to one of hundreds of different externally oriented oligosaccharide structures (PubMed:10430909). Glycosphingolipids are essential components of membrane microdomains that mediate membrane trafficking and signal transduction (PubMed:10430909). They are implicated in many fundamental cellular processes, including growth, differentiation, migration, morphogenesis, cell-to-cell and cell-to-matrix interactions (PubMed:10430909). They are required for instance in the proper development and functioning of the nervous system (PubMed:16109770). As an example of their role in signal transduction, they regulate the leptin receptor/LEPR in the leptin-mediated signaling pathway (PubMed:23554574). They also play an important role in the establishment of the skin barrier regulating keratinocyte differentiation and the proper assembly of the cornified envelope (PubMed:17145749, PubMed:23748427). The biosynthesis of GSLs is also required for the proper intestinal endocytic uptake of nutritional lipids (PubMed:22851168). Catalyzes the synthesis of xylosylceramide/XylCer (such as beta-D-xylosyl-(1<->1')-N-acylsphing-4-enine) using UDP-Xyl as xylose donor (PubMed:33361282).|||The D1, D2, D3, (Q/R)XXRW motif is a critical part of the GCS active site, involved in catalysis and UDP-sugar binding. http://togogenome.org/gene/10090:Mylk ^@ http://purl.uniprot.org/uniprot/B1B1A8 ^@ Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Shc4 ^@ http://purl.uniprot.org/uniprot/Q6S5L9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates both Ras-dependent and Ras-independent migratory pathways in melanomas. Contributes to the early phases of agrin-induced tyrosine phosphorylation of CHRNB1.|||Expressed in both brain and skeletal muscle; widely expressed in brain namely olfactory bulb, cortex, hippocampus, striatum, thalamus, and brain stem (at protein level). Only expressed in melanomas. Weakly expressed in normal melanocytes and benign nevi. Highly expressed at the transition from radial growth phase to vertical growth phase and metastatic melanomas, when tumor cells acquire migratory competence and invasive potential.|||Interacts (via PID domain) with phosphorylated MUSK (via NPXY motif); undergoes tyrosine phosphorylation downstream of activated MUSK. Interacts with GRB2; the interaction is dependent of Tyr-422 phosphorylation and increased by EGF (By similarity).|||Phosphorylated; the phosphorylation is enhanced by EGF. Phosphorylation at Tyr-422 is required for the interaction with GRB2 (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Pfdn1 ^@ http://purl.uniprot.org/uniprot/Q9CQF7 ^@ Function|||Similarity ^@ Belongs to the prefoldin subunit beta family.|||Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. http://togogenome.org/gene/10090:Htr1f ^@ http://purl.uniprot.org/uniprot/Q02284|||http://purl.uniprot.org/uniprot/Q543V2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in hippocampus.|||G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.|||Membrane http://togogenome.org/gene/10090:Rorb ^@ http://purl.uniprot.org/uniprot/Q8R1B8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AF-2 (activation function-2) motif is required for recruiting coregulators containing the LXXLL motif, such as NCOA1, and control the transactivational activity.|||Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Expressed in inner and outer neuroblastic layer as well as in the ganglion cell layer of the developing retina. Expressed in bone marrow osteoprogenitor cells.|||Expressed in the lateral cortical plate at 18.5 dpc and only very weakly expressed by cortical neurons at 15.5 dpc. Expression progressively increases in layer IV neurons of the prospective somatosensory, visual and auditory cortices. At much lower levels, also expressed by scattered neurons in layer V in these areas. By P4, expression is striking in the whisker barrel cortex of the somatosensory cortex. During retinal development, isoform 1 is broadly expressed in between 13.5 dpc and P5 then declines and is maintained at lower levels into adulthood. At 15.5 dpc, is expressed in the immature cochlea, brainstem, spinal cord and cerebral cortex. Isoform 2 is first detected at low levels at late embryonic stages (18.5 dpc), the expression highly increases during the first postnatal week and is maintained during the adulthood.|||Induced by aging in bone marrow.|||Intron retention.|||Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4.|||Mice are blind, show juvenile ataxia, duck gait, hind paw clasping reflex as well as delayed onset of male fertility. They suffer a degeneration of the retina during postnatal development with severe defects in photoreceptor cell morphology. Mice display reduced anxiety and learned helplessness-related behaviors. They also show a significant increase of the circadian period. Knockouts for isoform 1 display duck gait and lack amacrine and horizontal cells with an excess of ganglion cells in the retina (PubMed:23652001).|||Monomer. Interacts with CRX.|||Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity.|||Nucleus|||nucleoplasm http://togogenome.org/gene/10090:Dscam ^@ http://purl.uniprot.org/uniprot/Q9ERC8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell adhesion molecule that plays a role in neuronal self-avoidance. Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells. Mediates within retinal amacrine and ganglion cell subtypes both isoneuronal self-avoidance for creating an orderly dendritic arborization and heteroneuronal self-avoidance to maintain the mosaic spacing between amacrine and ganglion cell bodies (PubMed:18216855, PubMed:19196994, PubMed:19945391). Receptor for netrin required for axon guidance independently of and in collaboration with the receptor DCC (PubMed:18585357). Might also collaborate with UNC5C in NTN1-mediated axon repulsion independently of DCC (PubMed:22685302). In spinal cord development plays a role in guiding commissural axons projection and pathfinding across the ventral midline to reach the floor plate upon ligand binding. Mediates intracellular signaling by stimulating the activation of MAPK8 and MAP kinase p38. Adhesion molecule that promotes lamina-specific synaptic connections in the retina: expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions (By similarity).|||Cell membrane|||Expressed in cortical and cerebellar neurons, in cells of the external and internal granular layer and of the Purkinje cell layer (at protein level) (PubMed:22685302). In the retina, expressed in dopaminergic and Nos1-positive amacrine cells and most retinal ganglion cells (at protein level). Expressed in the brain with highest levels in the cortex, olfactory bulb, hippocampus, thalamus, cerebellum and spinal cord. Expressed in the retinal ganglion layer (RGL).|||Expressed in embryo at 11 dpc. Expressed in the spinal cord, including the motor columns, motor axons, dorsal root ganglions, commissural axons and ventral funiculus at 11.5 dpc (at protein level). Detected at 15 dpc in the cortex and cerebellum and at postnatal day 2 in the cerebellum (at protein level) (PubMed:22685302). Expressed in the retinal ganglion layer (RGL) at 12.5, 14.5 and 17 dpc. Expressed in hindbrain (cerebellar plate neurons), midbrain and forebrain at 10 dpc. Expressed in follicles of vibrissae and nasal processes at 12 dpc. Expressed in eyes at 14 dpc. Expressed in spinal cord, heart, liver, forelimb and hindlimb, buds at 14 dpc onwards.|||Has been reported to enhance netrin-induced phosphorylation of PAK1 and FYN; and the interaction between DSCAM, PAK1 and RAC1 has been described. This article has been withdrawn by the authors.|||Homodimer; mediates homophilic interactions to promote cell adhesion (By similarity). Interacts with DCC; the interaction is abolished in response to NTN1 (PubMed:18585357). Interacts (via extracellular domain) with NTN1 (PubMed:18585357). Interacts (via extracellular domain) with UNC5C (via Ig-like C2-type domain) (PubMed:22685302). Interacts with PTK2 (PubMed:22685302). Interacts with FYN (PubMed:22685302).|||Ig-like C2-type domains 7 to 9 are sufficient for interaction with NTN1 and commissural axon outgrowth. The transmembrane domain is necessary for interaction with DCC.|||Phosphorylated at tyrosine residues (PubMed:22685302). Phosphorylation is enhanced by NTN1 (PubMed:22685302).|||Synapse|||The ganglion cell layer and developing inner plexiform layer in the retina are disorganised at postnatal day 4 (P4). This desorganisation persisted into adulthood in amacrine and ganglions cells. Amacrine and ganglion cell populations show fasciculated dendrites that self-crossed and their cell bodies are randomly distributed or pulled into clumps.|||axon|||dendrite|||growth cone http://togogenome.org/gene/10090:Angpt1 ^@ http://purl.uniprot.org/uniprot/O08538 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. Mediates blood vessel maturation/stability. Implicated in endothelial developmental processes later and distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme (By similarity).|||Early in development, at 9 dpc to 11 dpc, it is found most prominently in the heart myocardium surrounding the endocardium. Later, it becomes more widely distributed, most often in the mesenchyme surrounding developing vessels, in close association with endothelial cells.|||Embryonically lethal. Embryos die at about 12.5 dpc, due to important developmental defects of the endocardium and myocardium, plus generalized defects in vascular development.|||Homooligomer. Interacts with TEK/TIE2 (By similarity).|||Secreted http://togogenome.org/gene/10090:Nsmaf ^@ http://purl.uniprot.org/uniprot/O35242 ^@ Function ^@ Couples the p55 TNF-receptor (TNF-R55 / TNFR1) to neutral sphingomyelinase (N-SMASE). Specifically binds to the N-smase activation domain of TNF-R55. May regulate ceramide production by N-SMASE. http://togogenome.org/gene/10090:Prpf19 ^@ http://purl.uniprot.org/uniprot/Q99KP6 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat PRP19 family.|||Cytoplasm|||Expressed in white and brown adipose tissues, brain and to a lower extent in liver, kidney, muscle, lung and spleen (at protein level).|||Forced expression leads to suppression of neuronal differentiation, and on the contrary to stimulation of astroglial cell differentiation in retinoic acid-primed P19 cells (PubMed:16352598).|||Homotetramer. Component of activated, catalytic and post-catalytic spliceosomes. Component of the Prp19 complex/PRP19C/Nineteen complex/NTC and related complexes described as PRP19-CDC5L splicing complex and PSO4 complex. A homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2 constitute the core of those complexes. The interaction with CDC5L, PLRG1 and BCAS2 is direct within this core complex. At least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 are found in the Prp19 complex. The Prp19 complex associates with the spliceosome during its assembly and remodeling recruiting additional proteins. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Interacts with CWC22 and EIF4A3 in an RNA-independent manner. Interacts with RPA1 and RPA2; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it interacts with the replication protein A complex (RPA). Interacts with SETMAR; required for SETMAR recruitment to site of DNA damage. Interacts with U2AF2; the interaction is direct and recruits the Prp19 complex to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA. Interacts with PRPF3. Interacts with APEX1, DNTT and PSMB4. Interacts with KNSTRN (By similarity). Interacts with PSMC5 (PubMed:17349974). Isoform 2 (via N-terminus) interacts with PPIA. Isoform 2 does not interact with CDC5L (PubMed:16352598). Interacts with KHDC4 (By similarity). Interacts with USB1 (By similarity).|||Lipid droplet|||Nucleus|||The 7 WD repeats are necessary and sufficient to support interaction with the RPA complex.|||Ubiquitin-protein ligase which is a core component of several complexes mainly involved in pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex. Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries. The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair. Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response. May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA. As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process. In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:17349974). May play a role in the biogenesis of lipid droplets (PubMed:17118936). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity).|||Up-regulated in differentiating adipocytes (PubMed:17118936). Isoform 2 maximal expression level during the neural differentiation of P19 cells treated with retinoic acid (RA) is estimated to be 2.5-fold of the expression level of the untreated cells and it is detected 1-2 days after RA treatment and it decreases steeply thereafter to the basal level. Isoform 2 expression level increases steeply after 1 day of RA treatment and is estimated to be 4.2-fold of the original level at 0 hours (PubMed:16352598).|||nucleoplasm|||spindle http://togogenome.org/gene/10090:Mcmdc2 ^@ http://purl.uniprot.org/uniprot/E9Q956 ^@ Disruption Phenotype|||Function|||Tissue Specificity ^@ Mutant mice are viable and show no overt phenotype. However, both males and females are sterile. Males fail to produce spermatozoa, and formation of primordial follicles is disrupted in females.|||Plays an important role in meiotic recombination and associated DNA double-strand break repair.|||Predominantly expressed in the gonads and the brain. Not detected in the heart, lung, nor embryonic fibroblasts. http://togogenome.org/gene/10090:Tacc3 ^@ http://purl.uniprot.org/uniprot/Q6NV52|||http://purl.uniprot.org/uniprot/Q99LH8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TACC family.|||centrosome http://togogenome.org/gene/10090:Nyx ^@ http://purl.uniprot.org/uniprot/P83503 ^@ Developmental Stage|||Disease Annotation|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily.|||Defects in Nyx are the cause of the nob (no b-wave) phenotype which is characterized by a decreased sensitivity to light and an absence of the rod b-wave in electroretinograms. An 85-bp deletion in exon 3 results in the loss of 288 residues from the C-terminus of the protein.|||Expressed abundantly in retina with lower levels in brain, lung, spleen and testis. Not detected in kidney, heart or liver. In the retina, highest expression found in the inner nuclear layer and ganglion cell layer.|||Expressed during all stages of postnatal retinal development.|||extracellular matrix http://togogenome.org/gene/10090:Vmn2r44 ^@ http://purl.uniprot.org/uniprot/L7N2E1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Acvr2a ^@ http://purl.uniprot.org/uniprot/A2AI38|||http://purl.uniprot.org/uniprot/P27038|||http://purl.uniprot.org/uniprot/Q8BRV4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Brain, testis, intestine, liver and kidney.|||Cell membrane|||Membrane|||On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. Mediates induction of adipogenesis by GDF6 (PubMed:23527555).|||Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:10681527). Interacts with MAGI2/ARIP1 (PubMed:10681527). Interacts with type I receptor ACVR1 (By similarity). Interacts with BMP7 (By similarity). Interacts with TSC22D1/TSC-22 (By similarity). http://togogenome.org/gene/10090:Abhd8 ^@ http://purl.uniprot.org/uniprot/Q8R0P8 ^@ Caution|||Similarity ^@ Belongs to the AB hydrolase superfamily.|||It is uncertain whether Met-1 or Met-7 is the initiator. http://togogenome.org/gene/10090:Erg ^@ http://purl.uniprot.org/uniprot/A0A384DVA0|||http://purl.uniprot.org/uniprot/B7ZND4|||http://purl.uniprot.org/uniprot/E9PY05|||http://purl.uniprot.org/uniprot/P81270|||http://purl.uniprot.org/uniprot/Q3UQJ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ETS family.|||Cytoplasm|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with SETDB1.|||Nucleus|||Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure. http://togogenome.org/gene/10090:Slc8a2 ^@ http://purl.uniprot.org/uniprot/Q8K596 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.|||Calcium transport is down-regulated by Na(+) and stimulated by Ca(2+).|||Cell membrane|||Detected in kidney cortex, in distal convoluted tubules and connecting segments (PubMed:25498502). Detected in brain and spinal cord (at protein level) (PubMed:12818181). Detected in brain, especially in hippocampus CA1, CA2 and CA3 fiels, dentate gyrus, cerebellum and brain cortex (PubMed:12818181).|||Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:12818181). Contributes to cellular Ca(2+) homeostasis in excitable cells (PubMed:12818181). Contributes to the rapid decrease of cytoplasmic Ca(2+) levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory (PubMed:12818181). Plays a role in regulating urinary Ca(2+) and Na(+) excretion (PubMed:25498502).|||No obvious phenotype. In hippocampus pyramidal neurons, calcium exchange activity is reduced by about half, suggesting that other, additional calcium exchangers are active in these neurons. In these neurons, the neurotransmitter glutamate triggers a sharp increase in cellular Ca(2+) that does not depend on calcium exchanger activity. In contrast, the decrease to basal levels is mediated by calcium exchangers, and is considerably slower in mutant mice than in wild-type. Basal synaptic function is not impaired in mutant mice, but they display enhanced short-term plasticity and facilitated long-term potentiation, probably due to the slower decrease of Ca(2+) after an initial impulse. Mutant mice display an increased capacity for spatial learning and memory (PubMed:12818181). Heterozygous mutants show increased basal urine volume and increased urinary secretion of Ca(2+) and Na(+) (PubMed:25498502).|||The cytoplasmic Calx-beta domains bind the regulatory Ca(2+). The first Calx-beta domain can bind up to four Ca(2+) ions. The second domain can bind another two Ca(2+) ions that are essential for calcium-regulated ion exchange. http://togogenome.org/gene/10090:Ccn4 ^@ http://purl.uniprot.org/uniprot/O54775|||http://purl.uniprot.org/uniprot/Q3UFJ5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CCN family.|||Downstream regulator in the Wnt/Frizzled-signaling pathway (By similarity). Associated with cell survival. Adheres to skin and melanoma fibroblasts (By similarity). In vitro binding to skin fibroblasts occurs through the proteoglycans, decorin and biglycan (By similarity). Suppresses tumor growth in vivo.|||Highly expressed in kidney and lung. Lower levels in heart, brain, spleen, liver, skeletal muscle and testis. Expressed in low metastatic melanoma cells.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Tmem235 ^@ http://purl.uniprot.org/uniprot/B1AQL3 ^@ PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the PMP-22/EMP/MP20 family.|||Endoplasmic reticulum|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Fut1 ^@ http://purl.uniprot.org/uniprot/O09160|||http://purl.uniprot.org/uniprot/Q32MG3 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 11 family.|||Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose residue of glycoconjugates through an alpha(1,2) linkage leading to H antigen synthesis that is an intermediate substrate in the synthesis of ABO blood group antigens (PubMed:11368156, PubMed:14967068, PubMed:16884711). H antigen is essential for maturation of the glomerular layer of the main olfactory bulb, in cell migration and early cell-cell contacts during tumor associated angiogenesis (PubMed:16884711). Preferentially fucosylates soluble lactose and to a lesser extent, fucosylates glycolipids gangliosides GA1 and GM1a (PubMed:11368156, PubMed:14967068).|||Golgi stack membrane|||Homozygous mutant knockout mice for Fut1 develop normally, exhibit no gross phenotypic abnormalities and the Fucalpha(1-->2)Galbeta epitope is absent from the epithelia of the epididymis mice.|||In mouse, there are three genes (Fut1, Fut2 and Sec1) which encode galactoside 2-L-fucosyltransferase.|||In the adult, highly expressed in pancreas, testis and epididymis and to a lesser extent in thymus, lung, stomach, small intestine, colon, spleen and uterus. Not expressed in brain, heart, skeletal muscle, kidney, liver and bone marrow (PubMed:9355741). Expressed in epididymis and testis (PubMed:11368156).|||Membrane http://togogenome.org/gene/10090:Tgif2lx2 ^@ http://purl.uniprot.org/uniprot/Q8K5B9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Uros ^@ http://purl.uniprot.org/uniprot/P51163|||http://purl.uniprot.org/uniprot/Q3TPL3|||http://purl.uniprot.org/uniprot/Q3UG55|||http://purl.uniprot.org/uniprot/Q3UKR3 ^@ Function|||Similarity|||Subunit ^@ Belongs to the uroporphyrinogen-III synthase family.|||Catalyzes cyclization of the linear tetrapyrrole, hydroxymethylbilane, to the macrocyclic uroporphyrinogen III, the branch point for the various sub-pathways leading to the wide diversity of porphyrins. Porphyrins act as cofactors for a multitude of enzymes that perform a variety of processes within the cell such as methionine synthesis (vitamin B12) or oxygen transport (heme) (By similarity).|||Monomer. http://togogenome.org/gene/10090:Rnf13 ^@ http://purl.uniprot.org/uniprot/O54965|||http://purl.uniprot.org/uniprot/Q3UTG4|||http://purl.uniprot.org/uniprot/Q8CB78 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoubiquitinated.|||E3 ubiquitin-protein ligase that regulates cell proliferation (PubMed:19292867). Involved in apoptosis regulation (By similarity). Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA (By similarity). Also involved in protein trafficking and localization (By similarity).|||Endoplasmic reticulum membrane|||Expressed in the brain, heart, kidney, liver and spleen. Higher expression in adult tissues compared to the embryonic counterparts.|||Interacts with ERN1.|||Late endosome membrane|||Lysosome membrane|||Membrane|||N-glycosylated and also modified with chondroitin sulfate.|||Nucleus inner membrane|||The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis. http://togogenome.org/gene/10090:Podnl1 ^@ http://purl.uniprot.org/uniprot/Q6P3Y9 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class V subfamily.|||Detected in bone where it is expressed in osteoblasts and newly formed bone matrix (at protein level). Also expressed weakly in osteoclasts (at protein level). Expressed strongly in calvaria, lung and femur, and weakly in kidney.|||N-glycosylated.|||extracellular matrix http://togogenome.org/gene/10090:Klf10 ^@ http://purl.uniprot.org/uniprot/O89091 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||By TGF-beta and GDNF. Expressed in a circadian manner in the liver with a high at ZT14-18 and a low at ZT2 (at protein level). Expressed in a circadian manner in the bone, kidney and skeletal muscle. Up-regulated in response to glucose.|||Male mice display postprandial and fasting hyperglycemia while female mice are normoglycemic but display higher plasma triglycerides.|||Nucleus|||Transcriptional repressor which binds to the consensus sequence 5'-GGTGTG-3'. May play a role in the cell cycle regulation (By similarity). Plays a role in the regulation of the circadian clock; binds to the GC box sequence in the promoter of the core clock component ARTNL/BMAL1 and represses its transcriptional activity. Regulates the circadian expression of genes involved in lipogenesis, gluconeogenesis, and glycolysis in the liver. Represses the expression of PCK2, a rate-limiting step enzyme of gluconeogenesis.|||Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Eif2b1 ^@ http://purl.uniprot.org/uniprot/Q3UZR8|||http://purl.uniprot.org/uniprot/Q99LC8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the eIF-2B alpha/beta/delta subunits family.|||Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.|||Complex of five different subunits; alpha, beta, gamma, delta and epsilon. http://togogenome.org/gene/10090:Dach2 ^@ http://purl.uniprot.org/uniprot/Q925Q8 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DACH/dachshund family.|||Expressed in embryo, and at lower levels in the newborn.|||From 8.5 to 14.5 dpc detected in nervous tissue. In the brain detected at 8.5 dpc within the prospective hindbrain, but not within the developing forebrain or midbrain. At 9.5 dpc expressed within the ventral prosencephalon, hindbrain and forebrain. Expression within the forebrain neuroectoderm flanked the optic vesicle with rostral and caudal restrictions. In addition, dorsal and ventral expression domains were observed within the hindbrain. At 10.5 to 12.5 dpc detected in the dorsal mesencephalon, in addition to the telencephalon and hindbrain. At 14.5 dpc visible in the olfactory bulbs. Detected from 9.5 to 12.5 dpc in the dorsal neural tube with the highest expression near the hindbrain. At 9.5 and 10.5 dpc detected in cells located in the dorsal and ventral neural tube and dorsal root ganglia. Detected during the development of the optic and the auditory systems. At 10.5 dpc, a small ring of ocular staining was observed suggesting expression in the lens pit. At 10.5 dpc expressed in the developing lens epithelium and in the mesenchyme surrounding the retina. However, expression in the lens placode ectoderm was not detected, suggesting that DACH2 is activated after lens vesicle formation. Low levels of expression could also be detected in the peripheral neuroretina at 10.5 and 12.5 dpc. Detected in the otic pit at 9.5 dpc and in the otic endolymphatic duct at 10.5, 11.5 and 12.5 dpc. From 10.5 to 14.5 dpc detected in the developing fore and hind limbs. At 10.5 and 11.5 dpc observed in the anterior and posterior margins and presumptive hand plate of the limb bud. At 9.5 and 10.5 dpc expressed in the limb. At 12.5 dpc is detected in the hand plate with strong expression at the margins of the limb plate. At 14.5 dpc detected in the hand plate and lateral edges of the digits. At 8.5 dpc expression was not detected in the developing somites. In contrast, from 9.5 to 12.5 dpc, expression is detected in a repeated pattern located lateral to the neural tube and in the interlimb bud region suggesting expression in somite derivatives. At 9.5 dpc detected in the forelimb dermamyotome. Also located along the lateral portion of the trunk and within a dorsal domain within the limb bud. At 10.5 dpc expressed in lateral and limb mesoderm. From 9.5 to 10.5 dpc detected in head mesenchyme and the branchial arches. At 9.5 and 10 dpc. expressed in the head mesoderm associated with the developing eye. At 10.5 dpc this pattern appears as a ring of expression surrounding the eye. At 11.5 dpc expression is still detectable in the branchial arches with strong expression at the cranial sinus. At 14.5 dpc mammary gland primordia. Detected in the nasal openings and vibrissae.|||Interacts with SIX6. Interacts with EYA2 (By similarity).|||Nucleus|||The DACHbox-N domain forms a structure containing a DNA binding motif similar to that of the forkhead/winged helix domain.|||Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator for SIX1 and SIX6. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter. Is recruited with SIX6 to the p27Kip1 promoter in embryonal retina. SIX6 corepression seems also to involve NCOR1, TBL1, HDAC1 and HDAC3. May be involved together with PAX3, SIX1, and EYA2 in regulation of myogenesis. In the developing somite, expression of DACH2 and PAX3 is regulated by the overlying ectoderm, and DACH2 and PAX3 positively regulate each other's expression. Probably binds to DNA via its DACHbox-N domain. http://togogenome.org/gene/10090:Kmt5b ^@ http://purl.uniprot.org/uniprot/Q3U8K7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar4-20 subfamily.|||Chromosome|||Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:28114273, PubMed:24049080, PubMed:15145825). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By similarity). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression (PubMed:15145825). Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions (PubMed:15145825). KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (PubMed:16612004, PubMed:15750587). Plays a role in myogenesis by regulating the expression of target genes, such as EID3 (PubMed:23720823). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273).|||Homodimer (PubMed:24049080). Interacts with HP1 proteins CBX1, CBX3 and CBX5 (PubMed:15145825). Interacts with RB1 family proteins RB1, RBL1 and RBL2 (PubMed:15750587, PubMed:16612004). Interacts (via C-terminus) with FRG1 (PubMed:23720823).|||Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196). A-196 is competitive with the histone peptide substrate H4K20me1 but non competitive with S-adenosyl-L-methionine.|||Nucleus|||Partial muscle-specific knockout mice display several signs of muscular dystrophy including necrosis and an increased number of centrally nucleated myofibers. RNAi-mediated knockdown in C2C12 muscle cells causes reduced myogenic differentiation of the cells. http://togogenome.org/gene/10090:Mknk2 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZX7|||http://purl.uniprot.org/uniprot/Q8CDB0 ^@ Activity Regulation|||Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Binds 1 zinc ion per monomer.|||Cytoplasm|||Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14 (By similarity). Dephosphorylated by PP2A.|||Inhibited by CGP57380 and staurosporine.|||Interacts with ESR2 and EIF4E in the nucleus (By similarity). Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation.|||PML body|||Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Enhances the formation of EIF4F complex in pachytene spermatocytes, thus promoting mRNA translation during spermatogenesis. Displays a high basal kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.|||Ubiquitously expressed in all tissues examined, with high levels in skeletal muscle and low levels in brain. http://togogenome.org/gene/10090:Gbp7 ^@ http://purl.uniprot.org/uniprot/Q91Z40 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||By IFNG/IFN-gamma and IFNB1/IFN-beta (PubMed:18025219). Up-regulated upon infection by T.gondii or L.monocytogenes (PubMed:18025219). Up-regulated in response to influenza virus A infection (PubMed:33408175).|||Cytoplasmic vesicle membrane|||Inhibited by orthovanadate, berylium fluoride and aluminum flouride.|||Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:18025219, PubMed:21551061, PubMed:31964735, PubMed:24739961). Hydrolyzes GTP to GMP in two consecutive cleavage reactions and predominantly uses GTP and not GDP or GMP as the substrate (PubMed:21551061, PubMed:31689351). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (PubMed:24739961). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (PubMed:24739961). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis, such as Gm12250/Irgb10: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (PubMed:24739961). Also promotes IFN-gamma-mediated host defense against bacterial infections by regulating oxidative responses and bacteriolytic peptide generation (PubMed:21551061). May help to assemble NADPH oxidase on phagosomal membranes by acting as a bridging protein between NADPH oxidase cytosolic subunits NCF2-NCF4 and the membrane subunits CYBA-CYBB (PubMed:21551061). Participates along with GBP1 in trafficking monoubiquinated protein cargo to autolysosomes for generating ubiquitin-derived antimicrobial peptides (PubMed:21551061). Facilitates influenza A virus replication by inhibiting the activation of NF-kappaB and JAK-STAT signaling pathways and the expression of type I, type III interferons and pro-inflammatory cytokines (By similarity). Confers protection to several pathogens, including the bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii (PubMed:18025219, PubMed:21551061, PubMed:31964735). Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite (PubMed:31964735).|||Mice show a dramatic susceptibility to T. gondii infection, resulting in rapid death of infected mice in the acute phase of infection. A significantly increased parasite load seen in the spleen, liver and the peritoneal fluid, with markedly elevated production of pro-inflammatory cytokines and development of severe ascites.|||Monomer and dimer (PubMed:31689351). Interacts with CYBA, CYBA-CYBB complex and ATG4B (PubMed:21551061). Interacts (via GB1/RHD3-type G domain) with NCF2 and NCF2-NCF4 complex (PubMed:21551061). http://togogenome.org/gene/10090:Prrt2 ^@ http://purl.uniprot.org/uniprot/E9PUL5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system. In hippocampal neurons, in presynaptic terminals, plays an important role in the final steps of neurotransmitter release, possibly by regulating Ca(2+)-sensing (PubMed:27052163). In the cerebellum, may inhibit SNARE complex formation and down-regulate short-term facilitation (PubMed:29056747).|||At the mRNA level, expressed at low levels in the developing brain before 16 dpc. Expression markedly increases during early postnatal stages with a peak at P14. At this stage, expressed throughout the brain, with high levels in the cerebral cortex (cortical layers), hippocampus and cerebellum (granule cells and Purkinje cell layers). Progressively declines to relatively low levels in adulthood. At the protein level, first detected at very low levels at 17.5 dpc. Expression increases at early postnatal stages in the cerebral cortex, hippocampus and cerebellum. Expression increases to reach a plateau around P14, a period of intense synapse formation and rearrangement, and starts to slightly decrease around P90 (at protein level) (PubMed:27052163, PubMed:29056747).|||Belongs to the CD225/Dispanin family.|||Cell membrane|||Component of the outer core of AMPAR complex (PubMed:22632720, PubMed:25915028). AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (PubMed:22632720). Interacts with intersectin 1/ITSN1 (PubMed:26797119). Interacts with SNARE complex components, including SNAP25, STX1A, SYT1 and SYT2; this interaction may inhibit SNARE complex formation (PubMed:22832103, PubMed:27052163, PubMed:29056747).|||Mutant mice are normal at birth, but display paroxysmal movements at the onset of locomotion that persist in the adulthood. Adult animals present abnormal motor behaviors characterized by wild running and jumping in response to audiogenic stimuli that are ineffective in wild-type mice and an increased sensitivity to the convulsive effects of pentylentetrazol. Although the overall brain structure is not affected by the knockout, the thickness of the neocortex in young adult is significantly reduced in medial and caudal regions compared to their wild-type littermates. No significant differences are observed in the thickness of the CA1, CA3 and DG regions of the hippocampus, as well as for the molecular and granule layers of the cerebellum (PubMed:28007585). Mice with a conditional knockout in the central nervous system develop normally, but showed poor performance in motor coordination functions (PubMed:29056747).|||Neuron-specific expression throughout the brain, with the highest levels in the cerebellum, basal ganglia, hippocampus, substantia nigra, and neocortex (at protein level) (PubMed:22101681, PubMed:22243967, PubMed:22832103, PubMed:22632720, PubMed:25915028, PubMed:27052163, PubMed:27172900, PubMed:28007585, PubMed:29056747). Highly expressed also in spinal cord (at protein level) (PubMed:22101681, PubMed:22832103). Detected at very low levels in the heart, lung, kidney and skin (PubMed:22101681).|||Postsynaptic density membrane|||Presynaptic cell membrane|||Synapse|||axon|||dendritic spine|||synaptic vesicle membrane http://togogenome.org/gene/10090:Zyx ^@ http://purl.uniprot.org/uniprot/Q62523 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adhesion plaque protein. Binds alpha-actinin and the CRP protein. Important for targeting TES and ENA/VASP family members to focal adhesions and for the formation of actin-rich structures. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression (By similarity).|||Belongs to the zyxin/ajuba family.|||Cytoplasm|||Interacts, via the Pro-rich regions, with the EVH1 domains of ENAH, EVL and VASP. Interacts with the first LIM domain of TES. Interacts with SYNPO2 (By similarity).|||Nucleus|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Aspn ^@ http://purl.uniprot.org/uniprot/A6H6K1|||http://purl.uniprot.org/uniprot/Q99MQ4 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 12.5 dpc, it is present in the mandibular as well as maxillary components of the first branchial arch. Also detected in the thoracic body wall adjacent to the heart. At 13.5 dpc, it is detected in the mesenchyme lateral to Meckel's cartilage. Pronounced expression is observed in the perichondrium of the humerus, ribs, and scapula. At 14.5 dpc, it is detected in the mesenchymal condensations lateral to Meckel's cartilage, in the perichondrium surrounding the central cartilaginous elements of the vertebra and also in the dermal mesenchyme. At 15.5 dpc, it is expressed in the perichondrium/periosteum of the long bones (i.e. femur, tibia, and fibula), some of the flat bones at the base of the skull (i.e. sphenoid bone), ribs, clavicle, and vertebrae. Also detected in the intramembranous bones of the maxilla and mandible (alveolar bone) and a strong expression is observed in sagittal sections of the subcutaneous muscles or panniculus carnosus of the thorax, trunk, and head/ neck (platysma muscle) region. Very little expression is detected in the major parenchymal organs (with the exception of the large bronchi of the lung). Its expression is prominent in the developing mouse skeleton, particularly in the perichondrium/periosteum of cartilage/bone, and is also found in other specialized connective tissues such as tendon, sclera, the connective tissue sheath surrounding muscle and dermis. In the sclera of the eye it is first detected at 15.5 dpc and stronger expression was detected at 17.5 dpc.|||Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.|||Binds calcium and plays a role in osteoblast-driven collagen biomineralization activity (By similarity). Critical regulator of TGF-beta in articular cartilage and plays an essential role in cartilage homeostasis and osteoarthritis (OA) pathogenesis. Negatively regulates chondrogenesis in the articular cartilage by blocking the TGF-beta/receptor interaction on the cell surface and inhibiting the canonical TGF-beta/Smad signal. Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system. Inhibits BMP2-induced cytodifferentiation of PDL cells by preventing its binding to BMPR1B/BMP type-1B receptor, resulting in inhibition of BMP-dependent activation of SMAD proteins. Inhibits the interaction between TGFB1 and TGF-beta receptor type II in the presence of heparin/heparan sulfate in vitro.|||By TGFB1. Induction requires ALK5 kinase activity and SMAD3.|||Higher expression in heart, also detected in kidney, stomach, testes, and skin but only weakly in lung, skeletal muscle, small intestine, and thymus. Expressed specifically and predominantly in the periodontal ligament (PDL). During tooth development, strong expression is seen in the dental follicle, which is the progenitor tissue that forms cementum, alveolar bone, and the PDL. Expressed in the perichondria of the maxilla, mandible, vertebrae, and long bones. Predominantly expressed in the perichondrium/periosteum of long bones (at protein level).|||Interacts with type I collagen. DCN can inhibit collagen binding (By similarity). Interacts with TGFB1, TGFB2 and TGFB3. DCN, BGN, and FMOD inhibit binding to TGFB1. Interacts with BMP2. Interacts in vitro with type II collagen.|||The repeats LRR 9, LRR 10 and LRR 11 are involved in binding type I collagen. The poly-Asp region is involved in binding calcium (By similarity). The LRR 5 repeat can inhibit BMP2-induced cytodifferentiation and may be involved in the interaction with BMP2.|||extracellular matrix http://togogenome.org/gene/10090:Bcap29 ^@ http://purl.uniprot.org/uniprot/Q542A1|||http://purl.uniprot.org/uniprot/Q61334 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BCAP29/BCAP31 family.|||Endoplasmic reticulum membrane|||Highly expressed in brain and testis; detected at lower levels in thymus, spleen, liver, lung and bone marrow.|||Homodimer and heterodimer with BCAP31. Binds CASP8 as a complex containing BCAP31, BCAP29, BCL2 and/or BCL2L1. Interacts with VAMP3, VAMP1 and membrane IgD immunoglobulins. May interact with ACTG1 and non-muscle myosin II (By similarity).|||May play a role in anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi. May be involved in CASP8-mediated apoptosis (By similarity).|||Membrane|||Plays a role in the export of secreted proteins in the ER. http://togogenome.org/gene/10090:Cenpl ^@ http://purl.uniprot.org/uniprot/Q14A61 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CENP-L/IML3 family.|||Nucleus http://togogenome.org/gene/10090:Lsp1 ^@ http://purl.uniprot.org/uniprot/P19973 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Isoform 1 is expressed in normal mouse B and T-lymphocytes and in transformed B-cells but not (or in smaller amounts) in nine T-lymphoma lines tested. Isoform 2 is expressed in non-lymphoid cell lines (myocytes, stromal cells, fibroblasts).|||May play a role in mediating neutrophil activation and chemotaxis.|||Phosphorylated by casein kinase II, protein kinase C and MAPKAPK2. Phosphorylation by PKC induces translocation from membrane to cytoplasm. Phosphorylation by MAPKAPK2 may regulate neutrophil chemotaxis. http://togogenome.org/gene/10090:Thap11 ^@ http://purl.uniprot.org/uniprot/Q9JJD0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the THAP11 family.|||Cytoplasm|||First appears at the 2-cell stage, intensifies during the 8-cell and compact morula stages, but subsides in the blastocyst.|||Interacts (via coiled coil domain) with HCFC1.|||Mainly restricted to pluripotent cells of the developing embryo, to oocytes, and to certain regions of the adult brain.|||Mice show periimplantational lethality and have defects in the inner cell mass. Conditional knockout prevents the growth of ES cells while forced expression allows ES cells to proliferate without differentiation under conditions that normally do not promote self-renewal.|||Nucleus|||Transcriptional repressor that plays a central role for embryogenesis and the pluripotency of embryonic stem (ES) cells. Sequence-specific DNA-binding factor that represses gene expression in pluripotent ES cells by directly binding to key genetic loci and recruiting epigenetic modifiers.|||Was named 'Ronin' (a masterless Japanese samurai) by PubMed:18585351 because of its lack of apparent relationship to known 'master' regulator of pluripotency. http://togogenome.org/gene/10090:Gm20812 ^@ http://purl.uniprot.org/uniprot/J3QPZ4 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Dcaf5 ^@ http://purl.uniprot.org/uniprot/Q80T85 ^@ Function|||Subunit ^@ Interacts with DDB1, CUL4A or CUL4B. Interacts with L3MBTL3 (PubMed:30442713). Interacts with SOX2 (PubMed:30442713). Interacts with DNMT1 (By similarity). Interacts with E2F1 (By similarity).|||Is a substrate receptor for the CUL4-DDB1 E3 ubiquitin-protein ligase complex (CRL4), involved in the ubiquitination of a set of methylated non-histone proteins, including SOX2 (PubMed:30442713). The complex CRL4-DCAF5 is also involved in the ubiquitination of methylated DNMT1 and E2F1 (By similarity). http://togogenome.org/gene/10090:Fnip1 ^@ http://purl.uniprot.org/uniprot/Q68FD7 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FNIP family.|||Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:23582324). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (By similarity). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (By similarity). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (By similarity). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (By similarity). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (By similarity). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (By similarity). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (PubMed:32941802). Required for B-cell development (PubMed:22709692, PubMed:27303042).|||GlcNAcylation at Ser-937 by OGT following dephosphorylation by protein phosphatase 5 (PP5) promotes ubiquitination and degradation by the proteasome.|||Homodimer and homomultimer (By similarity). Heterodimer and heteromultimer with FNIP2 (By similarity). Interacts with FLCN (via C-terminus) (By similarity). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with HSPCA and with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (AMPK) (By similarity). Phosphorylated FLCN and AMPK are preferentially bound (By similarity). Interacts with HSP70, STIP1, PTGES3, CDC37, BRAF, GCR and CDK4 (By similarity). Interacts with HSP90AA1; the interaction inhibits HSP90AA1 ATPase activity (By similarity). Interacts with ATP2A2 (PubMed:35412553).|||Lysosome membrane|||Mice develop normally but display defects in B-cell development independent of mTOR activity (PubMed:22709692, PubMed:27303042). B-cell development defects result from rapid caspase-induced pre-B cell death (PubMed:22709692). Heterozygous mice show caused a loss of marginal zone B-cells (PubMed:27303042). Mice also develop cardiomyopathy characterized by left ventricular hypertrophy and elevated AMPK activity (PubMed:25775561, PubMed:27303042). Mice do not show strong susceptibility to kidney neoplasia (PubMed:22709692, PubMed:25775561). They however display slightly enlarged kidney size and slightly increased renal cyst formation, characterized by decreased AMPK activation, increased mTOR activation and metabolic hyperactivation (PubMed:29897930). Conditional deletion in adipocytes promotes browning of white adipose tissue (PubMed:35412553). Mice lacking both Fnip1 and Fnip2 show enlarged polycystic kidneys (PubMed:25775561).|||Oxidation of the Cys degron in normal conditions promotes its stabilization by preventing recognition and ubiquitination by the CRL2(FEM1B) complex.|||Phosphorylated by AMPK in response to energetic stress (PubMed:37079666). Phosphorylation by AMPK in response to mitochondrial damage promotes inactivation of the non-canonical mTORC1 signaling, nuclear translocation of TFEB and TFE3, inducing transcription of lysosomal or autophagy genes (PubMed:37079666). Sequential phosphorylation by CK2 promotes its gradual interaction with HSP90AA1/Hsp90 (By similarity). Priming phosphorylation at Ser-937 is followed by relay phosphorylation at Ser-938, Ser-940, Ser-945 and Ser-947, promoting its gradual interaction with HSP90AA1/Hsp90 (By similarity). This leads to incremental inhibition of HSP90AA1/Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients (By similarity). Dephosphorylated by protein phosphatase 5 (PP5), promoting glycosylation by OGT (By similarity).|||The KY-finger orients the Cys degron for ubiquitination by the CRL2(FEM1B) complex.|||Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties at Lys-1118 following glycosylation by OGT, leading to its degradation by the proteasome (By similarity). Ubiquitinated by the CRL2(FEM1B) complex in response to reductive stress: reductive stress causes reduction of the conserved Cys degron in FNIP1, followed by zinc-binding, zinc acting as a molecular glue for recognition by the CRL2(FEM1B) complex (PubMed:32941802, PubMed:34562363). Ubiquitination leads to FNIP1 degradation, and activation of mitochondria to recalibrate reactive oxygen species (ROS) (PubMed:32941802, PubMed:34562363).|||cytosol http://togogenome.org/gene/10090:Cyp2b9 ^@ http://purl.uniprot.org/uniprot/P12790 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Slc6a18 ^@ http://purl.uniprot.org/uniprot/A0A217FL56|||http://purl.uniprot.org/uniprot/O88576 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals lacking this protein exhibit no gross abnormalities and grow to adulthood, although they do exhibit hypertension. The elevated blood pressure appears to be attributable to a decreased level of renal glycine. High-affinity renal reabsorption of glycine is eliminated and intrarenal glycine concentration is reduced.|||Apical cell membrane|||Barely detectable at post natal day 0, reaching maximum expression after the third week of life.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A18 subfamily.|||Cell membrane|||Expressed predominantly in kidney.|||Human SLC6A18 has been shown to be an inactive protein.|||Interacts with CLTRN; this interaction regulates the trafficking of SLC6A18 to the cell membrane and its activity.|||Membrane|||Symporter that transports one amino acid molecule together with two sodium and one chloride ions in kidneys and plays a role in the neutral amino acids reabsorption (PubMed:19478081, PubMed:26240152, PubMed:20377526). Preferentially transports neutral amino acids such as L-glycine and L-alanine but also other neutral amino acids (PubMed:19478081, PubMed:26240152, PubMed:20377526). Required CLTRN for cell surface expression and for its amino acid transporter activity (PubMed:26240152, PubMed:20377526). The transport mechanism is pH-independent (PubMed:19478081). http://togogenome.org/gene/10090:Nudt16 ^@ http://purl.uniprot.org/uniprot/Q6P3D0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. NUDT16 subfamily.|||Binds 3 or 4 divalent metal cations. Acts specifically on U8 snoRNA with magnesium as cofactor. Has broad substrate specificity with bound manganese or cobalt (in vitro).|||Cytoplasm|||Expressed in brain, testis, spleen, lung, heart, liver, kidney and muscle (at protein level).|||Homodimer.|||Nucleus|||RNA-binding and decapping enzyme that catalyzes the cleavage of the cap structure of snoRNAs and mRNAs in a metal-dependent manner. Part of the U8 snoRNP complex that is required for the accumulation of mature 5.8S and 28S rRNA. Has diphosphatase activity and removes m7G and/or m227G caps from U8 snoRNA and leaves a 5'monophosphate on the RNA. Catalyzes also the cleavage of the cap structure on mRNAs. Does not hydrolyze cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG). Also hydrolysis m7G- and m227G U3-capped RNAs but with less efficiencies. Has broad substrate specificity with manganese or cobalt as cofactor and can act on various RNA species. Binds to the U8 snoRNA; metal is not required for RNA-binding. May play a role in the regulation of snoRNAs and mRNAs degradation (By similarity). Acts also as a phosphatase; hydrolyzes the non-canonical purine nucleotides inosine diphosphate (IDP) and deoxyinosine diphosphate (dITP) as well as guanosine diphosphate (GDP), deoxyguanosine diphosphate (dGDP), xanthine diphosphate (XDP), inosine triphosphate (ITP) and deoxyinosine triphosphate (ITP) to their respective monophosphate derivatives and does not distinguish between the deoxy- and ribose forms. The order of activity with different substrates is IDP > dIDP >> GDP = dGDP > XDP = ITP = dITP. Binds strongly to GTP, ITP and XTP. Participates in the hydrolysis of dIDP/IDP and probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. Exhibits decapping activity towards NAD-capped RNAs and FAD-capped RNAs (By similarity). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (PubMed:32432673).|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Pcyox1 ^@ http://purl.uniprot.org/uniprot/Q3UYP2|||http://purl.uniprot.org/uniprot/Q9CQF9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the prenylcysteine oxidase family.|||Highly expressed in the liver, kidney, heart and brain.|||Lysosome|||Mice are healthy and fertile, but show an accumulation of prenylcysteines within cells (PubMed:12151402). Significant accumulation of both farnesylcysteine and geranylgeranylcysteine in the brain and liver (PubMed:12151402).|||Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine (PubMed:12151402). Only active against free prenylcysteines and not prenylcysteine residues within prenylated proteins or peptides (By similarity). Involved in the final step in the degradation of prenylated proteins, by degrading prenylcysteines after the protein has been degraded (PubMed:12151402). http://togogenome.org/gene/10090:Col11a1 ^@ http://purl.uniprot.org/uniprot/Q61245 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibrillar collagen family.|||Defects in Col11a1 are associated with chondrodysplasia, an autosomal recessive disease characterized by skeletal defects caused by abnormalities in the cartilage of limbs, ribs, mandibles and trachea.|||May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.|||N-glycosylated.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||Trimers composed of three different chains: alpha 1(XI), alpha 2(XI), and alpha 3(XI). Alpha 3(XI) is a post-translational modification of alpha 1(II). Alpha 1(V) can also be found instead of alpha 3(XI)=1(II) (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Sdhaf3 ^@ http://purl.uniprot.org/uniprot/Q0VF92|||http://purl.uniprot.org/uniprot/Q8BQU3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I LYR family. SDHAF3 subfamily.|||Interacts with Sdhb within an Sdha-Sdhb subcomplex.|||Interacts with the iron-sulfur protein subunit within the SDH catalytic dimer.|||Mitochondrion matrix|||Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Promotes maturation of the iron-sulfur protein subunit Sdhb of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF1.|||Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Promotes maturation of the iron-sulfur protein subunit of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF1. http://togogenome.org/gene/10090:Adam7 ^@ http://purl.uniprot.org/uniprot/O35227 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a result of decreased egg fertilization male knockout mice produce a 15% reduced litter size whereas female knockout mice are unaffected (PubMed:26246218). No difference in male gross organ morphology (PubMed:26246218). Reduced epithelial cell heights in the caput regions of the epididymis, resulting in increased circumferences of the epididymal lumina (PubMed:26246218). Infrequent histological abnormalities can be found in the caput epididymis, such as sperm granulomas and mineralization-like features (PubMed:26246218). Increased frequency of intraepithelial vacuoles and hyperplasia found in the cauda epididymis (PubMed:26246218). Sperm obtained from the uterus of mated females show morphologically abnormal flagella with repeated bending and zigzag patterns (PubMed:26246218). Sperm incubated in vitro show reduced motility and abnormal flagella, additionally they show a reduction in overall levels of protein phosphotyrosine levels independent of capacitation state, resulting in an overall reduction in fertilization rate of 60% (PubMed:26246218). Decrease in protein levels of HSPA5 and ITM2B in both uncapacitated and capacitated sperm, and reduction in the levels of ADAM2 in capacitated sperm (PubMed:26246218).|||Expressed in both the head and tails of sperm (at protein level) (PubMed:26246218, PubMed:20945367). Expressed in the epididymis (at protein level) (PubMed:26246218). Abundantly expressed in the apical region of the proximal caput epididymal epithelium, with decreasing expression in the mid and distal caput epididymal epithelium (PubMed:9322939).|||Induced by testis factors and androgens including testosterone.|||Interacts with ITM2B in sperm; the interaction increases following capacitation (PubMed:20945367). Interacts with HSPA5 and CANX (PubMed:20945367).|||Membrane|||Required for normal male fertility via maintenance of epithelial cell morphology in the caput epididymis and subsequently correct epididymis lumen structure required for sperm development (PubMed:26246218). Plays a role in sperm motility, flagella morphology and tyrosine phosphorylation during sperm capacitance (PubMed:26246218). Plays a role in normal expression levels of HSPA5, ITM2B and ADAM2 in sperm both prior to and post-capacitation (PubMed:26246218). This is a non catalytic metalloprotease-like protein (Probable). http://togogenome.org/gene/10090:Gnpnat1 ^@ http://purl.uniprot.org/uniprot/Q9JK38 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the acetyltransferase family. GNA1 subfamily.|||Endosome membrane|||Golgi apparatus membrane|||Homodimer.|||Ubiquitous. Shows a strong differential expression pattern in adult hematopoietic precursor cells.|||Widely expressed at early stages of embryonic development but is confined to bones, skin and the hematopoietic system at later developmental stages. http://togogenome.org/gene/10090:Cops8 ^@ http://purl.uniprot.org/uniprot/Q8VBV7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CSN8 family.|||Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively (By similarity).|||Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 (PubMed:9707402). In the complex, it probably interacts directly with COPS3, COPS4 and COPS7 (COPS7A or COPS7B) (By similarity).|||Cytoplasm|||Expressed in embryonic stem (ES) cells and throughout early embryo development from zygote, preimplantation embryos, to post-implantation embryos. Predominantly expressed in the inner cell mass (ICM) of 3.5 dpc blastocyst and widely expressed in 9.5 dpc embryos.|||Nucleus|||Widely expressed. http://togogenome.org/gene/10090:Rexo2 ^@ http://purl.uniprot.org/uniprot/Q9D8S4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3'-to-5'exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides (PubMed:31588022). Binds and degrades longer oligonucleotides with a lower affinity (By similarity). Plays dual roles in mitochondria, scavenging nanoRNAs (small RNA oligonucleotides of <5 nucleotides) that are produced by the degradosome and clearing short RNAs that are generated by RNA processing (By similarity). Essential for correct initiation of mitochondrial transcription, degrading mitochondrial RNA dinucleotides to prevent RNA-primed transcription at non-canonical sites in the mitochondrial genome (PubMed:31588022). Essential for embryonic development (PubMed:31588022).|||Belongs to the oligoribonuclease family.|||Causes embryonic lethality before E8.5 (PubMed:31588022). Heart- and skeletal-muscle-specific knockout mice show elevated concentrations of the RNA dinucleotide pApA in the mitochondria purified from the heart (PubMed:31588022).|||Cytoplasm|||Homodimer (By similarity). Homotetramer (By similarity).|||Mitochondrion|||Mitochondrion intermembrane space|||Mitochondrion matrix|||Nucleus http://togogenome.org/gene/10090:Dnase2b ^@ http://purl.uniprot.org/uniprot/Q9QY48 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the DNase II family.|||Highly expressed in the eye lens. Detected in liver, but not in the other tissues tested.|||Hydrolyzes DNA under acidic conditions. Does not require divalent cations for activity. Participates in the degradation of nuclear DNA during lens cell differentiation.|||Inhibited by aurintricarboxylic acid and Zn(2+).|||Lysosome http://togogenome.org/gene/10090:Zfp346 ^@ http://purl.uniprot.org/uniprot/Q9R0B7 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds with low affinity to dsDNA and ssRNA, and with high affinity to dsRNA, with no detectable sequence specificity (By similarity) (PubMed:10488071). May bind to specific miRNA hairpins (By similarity).|||Cytoplasm|||Expressed in all tissues tested, including heart, brain, spleen, lung, liver, muscle, kidney and testis. Exogenous expression induced apoptosis.|||Forms a heteromeric complex with XPO5 and ILF3. Found in a nuclear export complex with XPO5, RAN, ILF3, ZNF346 and double-stranded RNA. Interacts with XPO5. Interacts with ILF3 in an RNA-independent manner (By similarity).|||The zinc-finger domains are required for binding to dsRNA, and also for nuclear localization.|||nucleolus http://togogenome.org/gene/10090:Lyrm4 ^@ http://purl.uniprot.org/uniprot/Q8K215 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I LYR family.|||Homodimer. Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer (By similarity). Component of the cyteine desulfurase complex composed of NFS1, LYRM4 and NDUFAB1; this complex contributes to the stability and cysteine desulfurase activity of NFS1. Interacts with FXN; this interaction is nickel-dependent. Interacts with the cytoplasmic form of NFS1; the complex increases the stability of NFS1. Forms a complex with the cytoplasmic form of NFS1; this complex increases the stability and cysteine desulfurase activity of NFS1. Interacts with NFS1 (By similarity). Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (PubMed:21298097, PubMed:25597503).|||Mitochondrion|||Nucleus|||Stabilizing factor, of the core iron-sulfur cluster (ISC) assembly complex, that regulates, in association with NDUFAB1, the stability and the cysteine desulfurase activity of NFS1 and participates in the [2Fe-2S] clusters assembly on the scaffolding protein ISCU (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May also participates in the iron-sulfur protein biogenesis in the cytoplasm through its interaction with the cytoplasmic form of NFS1 (By similarity). http://togogenome.org/gene/10090:Zfp174 ^@ http://purl.uniprot.org/uniprot/B9EJW5 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Tssc4 ^@ http://purl.uniprot.org/uniprot/Q9JHE7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TSSC4 family.|||Cytoplasm|||Expressed in embryo at 12.5 dpc and 16.5 dpc.|||Expressed in placenta. Widely expressed in embryo and newborn.|||Interacts in a RNA-independent manner with distinct U5 snRNP-containing complexes, the mono-U5 snRNP and the post-splicing U5 snRNP-PRPF19 complex. Interacts with SNRNP200; the interaction is direct, excludes recruitment of C9ORF78 and WBP4 to SNRNP200 and negatively regulates its RNA helicase activity. Interacts with PRPF8; the interaction is direct.|||Nucleus|||Protein associated with the U5 snRNP, during its maturation and its post-splicing recycling and which is required for spliceosomal tri-snRNP complex assembly in the nucleus. Has a molecular sequestering activity and transiently hinders SNRNP200 binding sites for constitutive splicing factors that intervene later during the assembly of the spliceosome and splicing. Together with its molecular sequestering activity, may also function as a molecular adapter and placeholder, coordinating the assembly of the U5 snRNP and its association with the U4/U6 di-snRNP. http://togogenome.org/gene/10090:Srsf9 ^@ http://purl.uniprot.org/uniprot/Q9D0B0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Extensively phosphorylated on serine residues in the RS domain.|||Interacts with KHDRBS3/SLM-2 (PubMed:11118435). Interacts with HABP4. Interacts with NOL3/ARC/NOP30, NSEP1/YB-1/YB1, SAFB/SAFB1, SRSF6/SFRS6, TRA2B/SFRS10 and C1QBP. May also interact with DUSP11/PIR1 (By similarity).|||Nucleus|||Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10 (By similarity). http://togogenome.org/gene/10090:Adgrf1 ^@ http://purl.uniprot.org/uniprot/Q8VEC3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Expressed in liver, kidney and adrenal gland. In kidney strong expression in the renal pelvis and the ureter.|||Glycosylated.|||Mice lacking Adgrf1 show no visible phenotype.|||Orphan receptor. http://togogenome.org/gene/10090:Wfdc15b ^@ http://purl.uniprot.org/uniprot/Q9JHY4 ^@ Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Antibacterial protein which inhibits the growth of E.coli and S.aureus.|||By intranasal administration of S.pneumoniae.|||Constitutively expressed in kidney and epididymis.|||Secreted http://togogenome.org/gene/10090:Ldaf1 ^@ http://purl.uniprot.org/uniprot/Q922Z1 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LDAF1 family.|||Endoplasmic reticulum membrane|||In liver with hepatic adiposis caused by PPAR gamma 1 overexpression (PubMed:15589683). Up-regulated during adipogenesis (PubMed:30901948).|||Interacts with BSCL2/seipin to form an oligomeric complex.|||Lipid droplet|||Plays an important role in the formation of lipid droplets (LD) which are storage organelles at the center of lipid and energy homeostasis (By similarity). In association with BSCL2/seipin, defines the sites of LD formation in the endoplasmic reticulum (By similarity).|||Prominently expressed in the heart and kidney. Expressed at higher levels in white fat as compared to brown fat and skeletal muscle. Expressed at lower levels in lung, liver and testis. http://togogenome.org/gene/10090:Gipc1 ^@ http://purl.uniprot.org/uniprot/Q9Z0G0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GIPC family.|||Cytoplasm|||Detected already at 4.5 dpc, expression peaks at 11.5-12.5 dpc and gradually declines to its adult levels by 18.5 dpc.|||Inhibits endothelial cell migration (in vitro). May be involved in G protein-linked signaling (By similarity).|||Interacts with GLUT1 (C-terminus), ACTN1, KIF1B, MYO6 and PLEKHG5 (By similarity). Interacts with RGS19 C-terminus. Interacts with SDC4/syndecan-4 and SEMA4C/semaphorin-4C.|||Membrane|||Widely expressed. http://togogenome.org/gene/10090:Sacs ^@ http://purl.uniprot.org/uniprot/Q9JLC8 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Brain (at protein level).|||Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins.|||Cytoplasm|||The J domain is functional and is able to stimulate E.coli dnaK ATPase activity.|||The ubiquitin-like domain mediates interaction with the proteasome. http://togogenome.org/gene/10090:Eci2 ^@ http://purl.uniprot.org/uniprot/Q9WUR2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species (PubMed:24344334). Has a preference for 3-trans substrates (By similarity).|||Acetylation of Lys-60 is observed in liver mitochondria from fasted mice but not from fed mice.|||Expressed in liver and kidney (at protein level).|||In the C-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.|||Mitochondrion|||Peroxisome matrix http://togogenome.org/gene/10090:Mob3b ^@ http://purl.uniprot.org/uniprot/Q8VE04 ^@ Function ^@ Modulates LATS1 expression in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. http://togogenome.org/gene/10090:Fbxo33 ^@ http://purl.uniprot.org/uniprot/Q8VE08 ^@ Function|||Subunit ^@ Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO33) formed of CUL1, SKP1, RBX1 and FBXO33. Interacts via its N-terminus with YBX1 CSD domain. Directly interacts with SKP1 and CUL1 (By similarity).|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. Recognizes YBX1. http://togogenome.org/gene/10090:Mbd5 ^@ http://purl.uniprot.org/uniprot/B1AYB6 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds to heterochromatin. Does not interact with either methylated or unmethylated DNA (in vitro) (By similarity).|||Both MBD and PWWP domains are necessary for chromocentric localization.|||Chromosome|||Expressed in embryo at 7, 11, 15 and 17 dpc.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Klhl15 ^@ http://purl.uniprot.org/uniprot/A2AAX3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Dimerization does not affect PPP2R5B-binding, but is required for its proteasomal degradation. Interacts with CUL3. Directly interacts with PPP2R5B; this interaction leads to PPP2R5B proteasomal degradation. Interacts with RBBP8/CtIP; this interaction leads to RBBP8 proteasomal degradation. Interacts with PACMP micropeptide; interaction prevents ubiquitination and degradation of RBBP8/CtIP.|||Nucleus|||Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex. Acts as an adapter for CUL3 to target the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits and regulating PP2A holoenzyme composition. Acts as an adapter for CUL3 to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR). http://togogenome.org/gene/10090:Cct6b ^@ http://purl.uniprot.org/uniprot/B1AT05|||http://purl.uniprot.org/uniprot/Q497N0|||http://purl.uniprot.org/uniprot/Q61390|||http://purl.uniprot.org/uniprot/Q8BVT1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter.|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis.|||Cytoplasm|||Testis specific. http://togogenome.org/gene/10090:Or2ag2b ^@ http://purl.uniprot.org/uniprot/Q9D3U9|||http://purl.uniprot.org/uniprot/Q9D4F9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Hspa1a ^@ http://purl.uniprot.org/uniprot/Q3TU85|||http://purl.uniprot.org/uniprot/Q61696 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 70 family.|||Component of the CatSper complex (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Interacts with CHCHD3, DNAJC7, IRAK1BP1, PPP5C and TSC2 (By similarity). Interacts with TERT; the interaction occurs in the absence of the RNA component, TERC, and dissociates once the TERT complex has formed (By similarity). Interacts with METTL21A (By similarity). Interacts with DNAAF2 (PubMed:19052621). Interacts with TRIM5 (via B30.2/SPRY domain) (By similarity). Interacts with PRKN (By similarity). Interacts with FOXP3 (PubMed:23973223). Interacts with NOD2; the interaction enhances NOD2 stability (By similarity). Interacts with DNAJC9 (via J domain) (By similarity). Interacts with ATF5; the interaction protects ATF5 from degradation via proteasome-dependent and caspase-dependent processes (By similarity). Interacts with RNF207 (via the C-terminus); this interaction additively increases KCNH2 expression (By similarity). Interacts with HSF1 (via transactivation domain); this interaction results in the inhibition of heat shock- and HSF1-induced transcriptional activity during the attenuation and recovery phase period of the heat shock response. Interacts with NAA10, HSP40, HSP90 and HDAC4. The acetylated form and the non-acetylated form interact with HOPX and STUB1 respectively. Interacts with NEDD1 and SMAD3. Interacts (via NBD) with BAG1, BAG2, BAG3 and HSPH1/HSP105. Interacts with DNAJC8 (By similarity). Interacts with NLRP12. Interacts with PGLYRP (PubMed:14585845).|||Cytoplasm|||In response to cellular stress, acetylated at Lys-77 by NA110 and then gradually deacetylated by HDAC4 at later stages. Acetylation enhances its chaperone activity and also determines whether it will function as a chaperone for protein refolding or degradation by controlling its binding to co-chaperones HOPX and STUB1. The acetylated form and the non-acetylated form bind to HOPX and STUB1 respectively. Acetylation also protects cells against various types of cellular stress.|||Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1. Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation. Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle. Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation. Negatively regulates heat shock-induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response.|||Nucleus|||Secreted|||The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.|||centrosome http://togogenome.org/gene/10090:Ranbp2 ^@ http://purl.uniprot.org/uniprot/Q9ERU9 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RanBP2 E3 ligase family.|||Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited.|||Despite the presence of a PPIase cyclophilin-type domain, it has probably no peptidyl-prolyl cis-trans isomerase activity.|||E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Binds single-stranded RNA (in vitro). May bind DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1. Inhibits EIF4E-dependent mRNA export. Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB. Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity.|||Nucleus|||Nucleus envelope|||Nucleus membrane|||Part of the nuclear pore complex (By similarity). Forms a complex with NXT1, NXF1 and RANGAP1 (By similarity). Forms a tight complex with RANBP1 and UBE2I (By similarity). Interacts with SUMO1 but not SUMO2 (By similarity). Interacts with sumoylated RANGAP1 (By similarity). Interacts with CDCA8 (By similarity). Interacts with PML (By similarity). Interacts with BICD2 (By similarity). Interacts with PRKN (PubMed:16332688). Interacts with MCM3AP (By similarity). Interacts with COX11 (By similarity).|||Polyubiquitinated by PRKN, which leads to proteasomal degradation.|||The PPIase cyclophilin-type domain has high structural similarity with PPIA, but has extremely low and barely detectable proline isomerase activity (in vitro) (By similarity). Only about half of the residues that surround the PPIA active site cleft are conserved.|||The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.|||nuclear pore complex http://togogenome.org/gene/10090:Or10ag60 ^@ http://purl.uniprot.org/uniprot/A0A1L1SQT2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or13a22 ^@ http://purl.uniprot.org/uniprot/Q8VGL3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lilrb4a ^@ http://purl.uniprot.org/uniprot/Q64281 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.|||Expressed on mast cells and natural killer cells (at protein level) (PubMed:8977169, PubMed:8977170, PubMed:11457897). Expressed on neutrophils (at protein level) (PubMed:14557414). Expressed on eosinophils (at protein level) (PubMed:17761953). Expressed on dendritic cells (at protein level) (PubMed:18792399). Expressed on memory and marginal zone B cells (at protein level) (PubMed:24935931). Expressed on CD8 T cells (at protein level) (PubMed:12682239). Expressed in the uterus of pregnant mice where it is detected at day 4.0 of pregnancy with levels dropping at day 4.5 (PubMed:9338594). Highly expressed in the luminal epithelium of uterine endometrium with lower levels in the glandular epithelium (PubMed:9338594).|||Induced by lipopolysaccharide on neutrophils (at protein level) (PubMed:14557414). Induced by IL6 and LIF (PubMed:9338594).|||Inhibitory receptor involved in the down-regulation of the immune response (PubMed:10026201, PubMed:24935931). Receptor for FN1 (PubMed:34089617). Receptor for integrin ITGAV/ITGB3 (PubMed:11323698). Inhibits IgE-mediated mast cell activation, at least in part through interaction with ITGAV/ITGB3 (PubMed:8855262, PubMed:10026201, PubMed:11457897, PubMed:11323698). Also inhibits KITLG/SCF-mediated mast cell activation (PubMed:12884301). Through interaction with ITGAV/ITGB3, inhibits antibody production by memory and marginal zone B cells, probably by suppressing their differentiation into plasma cells (PubMed:24935931). Inhibits IFNG production by CD8 T cells, CD4 T cells and natural killer cells (PubMed:12682239). Inhibits antigen presentation by dendritic cells to T cells, preventing T cell activation (PubMed:18792399). Inhibits lipopolysaccharide-mediated neutrophil-dependent vascular injury (PubMed:14557414). Suppresses the allergic inflammatory response by inhibiting infiltration of neutrophils and eosinophils and preventing mast cell degranulation (PubMed:17761953). Inhibits lysis by natural killer cells (PubMed:8977169).|||Interacts (when tyrosine phosphorylated) with SH2 domain-containing phosphatases PTPN6/SHP-1 and PTPN11/SHP-2; interaction with PTPN6 enhances inhibition of mast cell activation.|||No effect on fertility or litter size (PubMed:10982834, PubMed:11457897). Normal development of mast cells and natural killer cells (PubMed:10982834). Increased severity of local and systemic anaphylactic reactions (PubMed:11457897). Significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis with greater tissue swelling and mast cell degranulation, and significantly greater and faster death rate in active systemic anaphylaxis (PubMed:11457897). However, another study found no effect on mast cell activity with no increase in mast cell degranulation (PubMed:10982834). Macroscopic hemorrhages following intradermal injection of E.coli lipopolysaccharide with increased neutrophil numbers around the site of injection (PubMed:14557414). Normal B cell development and memory B cell formation but increased production by marginal zone and memory B cells of IgM after a primary immunization and of IgM, IgG1 and IgE after a secondary immunization (PubMed:24935931). Reduced ERK activation and reduced Prdm1/Blimp1 expression, indicative of suppression of plasma cell differentiation (PubMed:24935931). No effect on antigen uptake or cytokine production by dendritic cells but dendritic cells show enhanced antigen presentation to T cells and induce increased T cell stimulation (PubMed:18792399). Increased neutrophilia, eosinophilia and mast cell degranulation following ocular ragweed (RW) sensitization and challenge, and increased lung inflammation following RW sensitization and challenge (PubMed:17761953). Increased Kitlg/SCF-induced mast cell degranulation and tissue swelling (PubMed:12884301). Enhanced IFNG production by CD8 T cells, CD4 T cells and NK cells following viral infection (PubMed:12682239).|||Tyrosine phosphorylated. http://togogenome.org/gene/10090:Neurod2 ^@ http://purl.uniprot.org/uniprot/Q3TYB2|||http://purl.uniprot.org/uniprot/Q62414 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in dorsal and ventral parts of the lateral, basolateral and basomedial amygdala at 17 and 18 dpc (at protein level). Initially expressed in embryo at 11 dpc, with persistent expression in the nervous system until birth.|||Expressed in the external germinal layer (EGL) and internal granular layer (IGL) of the cerebellum (at protein level). Expressed in layers V and VI of the neocortex at postnatal day 1. Expressed in all layers of the neocortex at postnatal day 4. Strongly expressed in layer IV of the neocortex, particularly in the barrel cortex at postnatal day 7. Expressed in the CA1, CA2 and CA3 and dentate gyrus of the hippocampus and many nuclei such as the habenular thalamic nuclei, paraventricular hypothalamic nuclei, amygdala nuclei, and pyramidal nucleus. Expressed in granule cells, molecular layer neurons, and deep cerebella nuclei of the cerebellum. Expressed in brainstem neurons in the external cuneate nucleus and central gray.|||Interacts with TCF3, TCF4 and TCF12. Interacts with CDC20. Efficient DNA-binding and transcription activation require dimerization with another bHLH protein.|||Mice exhibit small brains, ataxia, reduced seizure threshold, growth failure, and postnatal premature death. Show excessive apoptosis in central nervous system. Lacks nuclei of the lateral and basolateral amygdala. Organization of cortical neurons into barrel structures is disrupted; thalamocortical axon terminals fail to segregate in the somatosensory cortex.|||Nucleus|||The C-terminal region is necessary for depolarization-induced and calcium-dependent transcription activation.|||Transcriptional regulator implicated in neuronal determination. Mediates calcium-dependent transcription activation by binding to E box-containing promoter. Critical factor essential for the repression of the genetic program for neuronal differentiation; prevents the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Induces transcription of ZEB1, which in turn represses neuronal differentiation by down-regulating REST expression. Plays a role in the establishment and maturation of thalamocortical connections; involved in the segregation of thalamic afferents into distinct barrel domains within layer VI of the somatosensory cortex. Involved in the development of the cerebellar and hippocampal granular neurons, neurons in the basolateral nucleus of amygdala and the hypothalamic-pituitary axis. Associates with chromatin to the DPYSL3 E box-containing promoter.|||Ubiquitinated by the APC/C complex; leading to its degradation in neurons. The CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation. http://togogenome.org/gene/10090:Or2y17 ^@ http://purl.uniprot.org/uniprot/Q8VGW9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Armcx6 ^@ http://purl.uniprot.org/uniprot/Q8K3A6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the eutherian X-chromosome-specific Armcx family.|||Highly expressed in the developing neural tissues, neural crest derivatives and hind limbs. Also widely expressed in the adult nervous tissue, especially in the forebrain, including the cerebral cortex, hippocampus and thalamus.|||May regulate the dynamics and distribution of mitochondria in neural cells.|||Mitochondrion|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Vmn1r61 ^@ http://purl.uniprot.org/uniprot/W4VSP5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rdh14 ^@ http://purl.uniprot.org/uniprot/Q9ERI6 ^@ Function|||Miscellaneous|||Similarity ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Retinol dehydrogenase with a clear preference for NADP. Displays high activity towards 9-cis, 11-cis and all-trans-retinol. Shows a very weak activity towards 13-cis-retinol. Has no activity towards steroids.|||Shows clear specificity for the pro-S hydrogen on C4 of NADPH and the pro-R hydrogen on C15 of retinols. http://togogenome.org/gene/10090:Tbkbp1 ^@ http://purl.uniprot.org/uniprot/A2A9T0 ^@ Function|||Subunit ^@ Adapter protein which constitutively binds TBK1 and IKBKE playing a role in antiviral innate immunity. Essential for the efficient induction of IRF-dependent transcription following infection with Sendai virus.|||Homodimer (PubMed:17568778). May form a heterodimer with NAP1. Interacts with TKB1 and IKBKE (PubMed:17568778). Weakly interacts with DDX3X (By similarity). http://togogenome.org/gene/10090:Srp54a ^@ http://purl.uniprot.org/uniprot/P14576 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GTP-binding SRP family. SRP54 subfamily.|||Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9 (By similarity). Interacts with RNPS1 (By similarity). Interacts with the SRP receptor subunit SRPRA (By similarity).|||Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (By similarity). As part of the SRP complex, associates with the SRP receptor (SR) component SRPRA to target secretory proteins to the endoplasmic reticulum membrane (By similarity). Binds to the signal sequence of presecretory proteins when they emerge from the ribosomes (By similarity). Displays basal GTPase activity, and stimulates reciprocal GTPase activation of the SR subunit SRPRA (By similarity). Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SR subunit SRPRA (By similarity). SR compaction and GTPase mediated rearrangement of SR drive SRP-mediated cotranslational protein translocation into the ER (By similarity). Requires the presence of SRP9/SRP14 and/or SRP19 to stably interact with RNA (By similarity). Plays a role in proliferation and differentiation of granulocytic cells, neutrophils migration capacity and exocrine pancreas development (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Nucleus speckle|||The M domain binds the 7SL RNA in presence of SRP19 and binds the signal sequence of presecretory proteins.|||The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA (By similarity). The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another (By similarity). SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (By similarity). http://togogenome.org/gene/10090:Gpr152 ^@ http://purl.uniprot.org/uniprot/Q8BXS7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Vmn1r208 ^@ http://purl.uniprot.org/uniprot/Q8R275 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Naa35 ^@ http://purl.uniprot.org/uniprot/Q6PHQ8 ^@ Caution|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues. Involved in regulation of apoptosis and proliferation of smooth muscle cells.|||Belongs to the MAK10 family.|||Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.|||Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||PubMed:16484612 decribes a Naa35/Egap-containing complex as evolutionary conserved NatC complex; however, the mMak3 protein investigated in this context corresponds to mammalian NAA50 and not NAA30 and its interaction with NAA35 is ambiguous. http://togogenome.org/gene/10090:Rasl11a ^@ http://purl.uniprot.org/uniprot/Q6IMB1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although highly related to the Ras family, lacks the conserved prenylation motif at the C-terminus, which serves to target Ras proteins to membrane compartments.|||Belongs to the small GTPase superfamily. Ras family.|||Interacts with UBF/UBTF.|||Regulator of rDNA transcription. Acts in cooperation UBF/UBTF and positively regulates RNA polymerase I transcription.|||nucleolus http://togogenome.org/gene/10090:Ccnf ^@ http://purl.uniprot.org/uniprot/P51944 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclin family. Cyclin AB subfamily.|||Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF (By similarity). Interacts with SKP1 (By similarity). Interacts with CUL1 (By similarity). Interacts with CCNB1; interaction is required for nuclear localization of CCNB1 (By similarity). Interacts with CCP110; this interaction leads to CCP110 ubiquitination and degradation via the proteasome pathway (By similarity). Interacts (via the Cyclin N-terminal domain) with MYBL2/BMYB (By similarity). Interacts with FZR1/CDH1 (via N-terminus) (By similarity). Interacts with RRM2 (via Cy motif and when phosphorylated at 'Thr-33'); the interaction occurs exclusively in G2 and early M (By similarity). Interacts with CDC6 (via Cy motif); the interaction takes place during G2 and M phase (By similarity).|||Death by 10.5 dpc, with many developmental anomalies due in part to failures in yolk sac and chorioallantoic placentation. Heterozygous mice are normal and fertile.|||Degraded when the spindle assembly checkpoint is activated during the G2-M transition. Degradation is not dependent on the proteasome or ubiquitin and depends on the C-terminal PEST sequence.|||Expression is activated by the FOXM1 transcription factor.|||Nucleus|||Phosphorylated just before cells enter into mitosis.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). The SCF(CCNF) E3 ubiquitin-protein ligase complex is an integral component of the ubiquitin proteasome system (UPS) and links proteasome degradation to the cell cycle (By similarity). Mediates the substrate recognition and the proteasomal degradation of various target proteins involved in the regulation of cell cycle progression and in the maintenance of genome stability (By similarity). Mediates the ubiquitination and subsequent proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication (By similarity). In G2, mediates the ubiquitination and proteasomal degradation of CDC6, thereby suppressing DNA re-replication and preventing genome instability (By similarity). Involved in the ubiquitination and degradation of the substrate adapter CDH1 of the anaphase-promoting complex (APC/C), thereby acting as an antagonist of APC/C in regulating G1 progression and S phase entry (By similarity). May play a role in the G2 cell cycle checkpoint control after DNA damage, possibly by promoting the ubiquitination of MYBL2/BMYB (By similarity).|||The D box motifs 1-4 (amino acid sequence RxxL) are involved in substrate binding, such as FZR1/CDH1, and may be ubiquitinated.|||The nuclear localization signals mediate the localization to the nucleus and are required for CCNB1 localization to the nucleus.|||Ubiquitinated by the anaphase-promoting complex (APC/C); leading to its degradation by the proteasome.|||centriole|||perinuclear region http://togogenome.org/gene/10090:Pla2g1b ^@ http://purl.uniprot.org/uniprot/Q9Z0Y2 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by trypsin cleavage in the duodenum. Can also be activated by thrombin or autocatalytically.|||Belongs to the phospholipase A2 family.|||Binds 1 Ca(2+) ion per subunit.|||Expressed in pancreas, liver, lung and spleen (PubMed:10066760). Expressed in EPCAM-positive intestinal epithelial cell (at protein level) (PubMed:29024642).|||Monomer or homodimer (By similarity). Interacts with PLA2R1; this interaction mediates intracellular signaling as well as clearance of extracellular PLA2G1B via endocytotic pathway (PubMed:10066760).|||Mutant mice are susceptible to H. polygyrus and N. brasiliensis infection, failing to expel larvae and retaining a sustained infection (PubMed:29024642). In response to high fat diet, mutant mice are resistant to hyperlipidemia associated with reduced hepatic very low density lipoprotein production and increased triglyceride-rich lipoprotein clearance (PubMed:21908646).|||Secreted|||Secretory calcium-dependent phospholipase A2 that primarily targets dietary phospholipids in the intestinal tract (By similarity). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation in the intestinal tract. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (By similarity). May act in an autocrine and paracrine manner (PubMed:10066760). Upon binding to the PLA2R1 receptor can regulate podocyte survival and glomerular homeostasis (By similarity). Has anti-helminth activity in a process regulated by gut microbiota (PubMed:29024642). Upon helminth infection of intestinal epithelia, directly affects phosphatidylethanolamine contents in the membrane of helminth larvae, likely controlling an array of phospholipid-mediated cellular processes such as membrane fusion and cell division while providing for better immune recognition, ultimately reducing larvae integrity and infectivity (PubMed:29024642).|||Up-regulated in EPCAM-positive intestinal epithelial cell upon helminth infection (PubMed:29024642). Up-regulated in intestinal epithelial organoids in response to stimulation with T-helper type 2 cytokines IL4 and IL13 (PubMed:29024642). http://togogenome.org/gene/10090:Angptl1 ^@ http://purl.uniprot.org/uniprot/Q640P2 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Mark1 ^@ http://purl.uniprot.org/uniprot/Q14DQ3|||http://purl.uniprot.org/uniprot/Q8VHJ5 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cell membrane|||Cytoplasm|||Inhibited by phosphorylation at Ser-219. Activated by phosphorylation on Thr-215 (By similarity).|||Interacts with MAPT/TAU.|||Phosphorylated at Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity (By similarity).|||Serine/threonine-protein kinase (By similarity). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (By similarity). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3).|||The KA1 domain mediates binding to phospholipids and targeting to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (By similarity).|||The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain (By similarity).|||cytoskeleton|||dendrite http://togogenome.org/gene/10090:Scg5 ^@ http://purl.uniprot.org/uniprot/P12961|||http://purl.uniprot.org/uniprot/Q3TT51 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway. Binds to inactive PCSK2 in the endoplasmic reticulum and facilitates its transport from there to later compartments of the secretory pathway where it is proteolytically matured and activated. Also required for cleavage of PCSK2 but does not appear to be involved in its folding. Plays a role in regulating pituitary hormone secretion. The C-terminal peptide inhibits PCSK2 in vitro.|||Belongs to the 7B2 family.|||Interacts with PCSK2/PC2 early in the secretory pathway. Dissociation occurs at later stages.|||Mice have no demonstrable Pcsk2/Pc2 activity, are deficient in processing islet hormones, and display hypoglycemia, hyperproinsulinemia and hypoglucagonemia, similar to Pcsk2 null mice. In contrast to Pcsk2 null mice, they develop Cushing's disease due to excessive secretion of corticotropin from the pituitary and die before 9 weeks, indicating a role for Sgne1 in control of peptide secretion from the pituitary.|||Proteolytically cleaved in the Golgi by a furin-like convertase to generate bioactive peptides.|||Secreted|||Sulfated on tyrosine residues. http://togogenome.org/gene/10090:Eif1ax ^@ http://purl.uniprot.org/uniprot/Q8BMJ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1.|||Component of the 43S pre-initiation complex (43S PIC), which is composed of the 40S ribosomal subunit, EIF1, eIF1A (EIF1AX), eIF3 complex, EIF5 and eIF2-GTP-initiator tRNA complex (eIF2 ternary complex). Interacts with EIF5; this interaction contributes to the maintenance of EIF1 within the open 43S PIC. Interacts through its C-terminal domain (CTD) with the CTD of EIF5B; from the location of the start codon by the 43S complex until the formation of the 80S complex.|||Cytoplasm http://togogenome.org/gene/10090:Rhox4g ^@ http://purl.uniprot.org/uniprot/Q2MDF7 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Mrpl50 ^@ http://purl.uniprot.org/uniprot/Q8VDT9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL50 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Tmed11 ^@ http://purl.uniprot.org/uniprot/A2RTW8|||http://purl.uniprot.org/uniprot/Q9D2R4|||http://purl.uniprot.org/uniprot/Q9D941 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the EMP24/GP25L family.|||Endoplasmic reticulum membrane|||Membrane|||Part of a complex whose function is to bind Ca(2+) to the ER membrane and thereby regulate the retention of ER resident proteins. http://togogenome.org/gene/10090:Alas1 ^@ http://purl.uniprot.org/uniprot/Q3V0B2|||http://purl.uniprot.org/uniprot/Q8VC19 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products.|||Homodimer (By similarity). Interacts (hydroxylated form) with VHL (By similarity).|||In normoxia, is hydroxylated at Pro-578, promoting interaction with VHL, initiating ubiquitination and subsequent degradation via the proteasome.|||Mitochondrion inner membrane|||Ubiquitinated; in normoxia following hydroxylation and interaction with VHL, leading to its subsequent degradation via the proteasome. http://togogenome.org/gene/10090:Kcng3 ^@ http://purl.uniprot.org/uniprot/P59053 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. G (TC 1.A.1.2) subfamily. Kv6.3/KCNG3 sub-subfamily.|||Cell membrane|||Cytoplasm|||Heterotetramer with KCNB1. Does not form homomultimers.|||Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1.|||The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. http://togogenome.org/gene/10090:Gm20854 ^@ http://purl.uniprot.org/uniprot/Q62461 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Ago2 ^@ http://purl.uniprot.org/uniprot/Q8CJG0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A phosphorylation cycle of C-terminal serine cluster (Ser-825-Ser-835) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target.|||Belongs to the argonaute family. Ago subfamily.|||Embryonic death with a strong defect in neural tube closure and apparent cardiac failure.|||Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.|||Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1 (PubMed:16357216). Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA (By similarity). Interacts with TRIM71 (PubMed:19898466, PubMed:22508726, PubMed:22735451). Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36 (By similarity). Interacts with RC3H1; the interaction is RNA independent (PubMed:25697406). Interacts with FAM172A (PubMed:29311329). Found in a complex composed of AGO2, CHD7 and FAM172A (PubMed:29311329). Interacts with SND1 and SYT11 (PubMed:24882364). Interacts with CLNK (PubMed:26009488). Interacts with GARRE1 (By similarity).|||Nucleus|||P-body|||Phosphorylation at Ser-388 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage.|||Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. Regulates lymphoid and erythroid development and function, and this is independent of endonuclease activity.|||The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).|||Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target.|||Ubiquitous expression in 9.5 day embryos with highest levels in forebrain, heart, limb buds, and branchial arches. http://togogenome.org/gene/10090:Plag1 ^@ http://purl.uniprot.org/uniprot/Q9QYE0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by lysine acetyltransferase EP300; which activates transcriptional capacity. Lysine residues that are sumoylated also seem to be target for acetylation (By similarity).|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||C2H2-type zinc fingers 3 interacts with DNA-binding site G-clusterinc fingers. C2H2-type zinc fingers 6 and 7 interact with DNA-binding site core sequence (By similarity).|||Expressed in heart, spleen, lung, kidney, brain, testis and epididymis but not in salivary glands.|||High fetal expression with a strong decline after birth. Expressed at 9.5 dpc and 10.5 dpc in nervous system with highest level in telencephalon, diencephalon, and midbrain, as well as regionalized expression in the neural tube, which is characteristic of genes involved in the specification of neuronal fates.|||Interacts with KPNA2, which escorts protein to the nucleus via interaction with nuclear localization signal. Interacts with E3 SUMO-protein ligase PIAS1, PIAS2 and PIAS4 (By similarity).|||Mice exhibit growth retardation with lower birth weight and disproportionally small seminal vesicles and ventral prostate as well as decreased fertility in both male and female. However, IGFII expression is normal in embryos.|||Mice overexpressing Plag1 develop normally with high Plag1 transgene expression in salivary glands, spleen and weak mammary gland detection. They develop salivary gland tumors with major pathological features of human pleimorphic adenomas at the age of 1-5 months.|||Mice with Plag1 overexpression targeted to salivary and mammary gland develop multifocal salivary gland tumors with pathological features of human pleimorphic adenomas at the age of 5 weeks, as well as mammary gland tumors at the age of 1 year. Plag1 overexpression in salivary gland are accompanied by increased IGFII expression. Besides features characteristic of benign pleimorphic adenomas, malignant characteristics are also observed in salivary gland tumors as well as metastasis to the lungs, reinforcing the tumorigenic role of Plag1.|||Neonate mice carrying a human myeloid leukemia translocation-associated fusion gene CBFB-MYH11, injected with a retrovirus (4070A), develop the pathology within 2-5 months due to few viral insertions in some genes, such as PLAG1. Insertions near the transcription start site of PLAG1 are predominant in the related tumors and probably participate in the transformation process. Plag1 is one candidate gene that can cooperate with CBFB-MYH11 for leukemogenesis in this mouse model.|||Nucleus|||Sumoylated with SUMO1; which inhibits transcriptional activity, but does not affect nuclear localization. Blockers of sumoylation pathway such as SENP3 and inactive UBE2I increases transcriptional capacity. Sumoylation is increased in the presence of PIAS1 (By similarity).|||Transcription factor whose activation results in up-regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Cooperates with CBFB-MYH11. http://togogenome.org/gene/10090:Kcnk13 ^@ http://purl.uniprot.org/uniprot/Q3TYG8|||http://purl.uniprot.org/uniprot/Q8R1P5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Homodimer.|||Membrane|||Potassium channel displaying weak inward rectification in symmetrical K(+) solution.|||The current is enhanced by arachidonic acid and inhibited by halothane. http://togogenome.org/gene/10090:Adarb2 ^@ http://purl.uniprot.org/uniprot/Q9JI20 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Brain specific.|||Lacks editing activity. It prevents the binding of other ADAR enzymes to targets in vitro, and decreases the efficiency of these enzymes. Capable of binding to dsRNA but also to ssRNA (By similarity).|||Nucleus http://togogenome.org/gene/10090:Tuba1c ^@ http://purl.uniprot.org/uniprot/P68373|||http://purl.uniprot.org/uniprot/Q52L87 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.|||Belongs to the tubulin family.|||Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle (PubMed:26446751). In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (PubMed:27102488).|||Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.|||Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.|||Minor alpha-tubulin expressed in all tissues.|||Nitration of Tyr-449 is irreversible and interferes with normal dynein intracellular distribution.|||Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:15890843). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity). Glutamylation is also involved in cilia motility (PubMed:23897886).|||Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. Cilia and flagella glycylation is required for their stability and maintenance. Flagella glycylation controls sperm motility (PubMed:33414192).|||The MREC motif may be critical for tubulin autoregulation.|||Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.|||Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (PubMed:16954346, PubMed:19564401). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules. In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).|||Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.|||cytoskeleton http://togogenome.org/gene/10090:Magi1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SUZ0|||http://purl.uniprot.org/uniprot/A0A0R4J0S6|||http://purl.uniprot.org/uniprot/Q3TQ86|||http://purl.uniprot.org/uniprot/Q4H4B4|||http://purl.uniprot.org/uniprot/Q4H4B5|||http://purl.uniprot.org/uniprot/Q6RHR9 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Interacts through its WW 2 domain with SYNPO and through its PDZ 5 domain with ACTN4. Interacts with cytoplasmic domain of ADGRB1. Interacts via its WW domains with DRPLA (By similarity). Interacts with ESAM, LRP2 and CXADR (PubMed:15383320, PubMed:11274227, PubMed:15304526). Isoform 2 interacts with CTNNB1 (PubMed:10772923). Interacts through its PDZ 1 domain with NET1 (PubMed:11350080). Interacts with ASIC3 and AMOT (By similarity) (PubMed:15317815). Interacts with FCHSD2 (By similarity). Interacts with IGSF5/JAM4 and through its PDZ 2 and 3 domains with NPHS1 forming a tripartite complex (By similarity). Interacts with DDN. May interact (via PDZ domain) with RAPGEF2 (By similarity). Interacts with DLL1 (PubMed:15509766). Interacts with KCNJ10 and possibly with KCNJ10/KCNJ16 heterodimer; this interaction may facilitate KCNJ10/KCNJ16 potassium channel expression at the basolateral membrane in kidney tubular cells (By similarity). Interacts with PRRG4 (via cytoplasmic domain) (By similarity).|||May play a role as scaffolding protein at cell-cell junctions. May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface.|||Membrane|||Nucleus|||Widely expressed, including kidney glomeruli.|||tight junction http://togogenome.org/gene/10090:Pcsk6 ^@ http://purl.uniprot.org/uniprot/E9Q4D0|||http://purl.uniprot.org/uniprot/F6XJP7 ^@ Similarity ^@ Belongs to the peptidase S8 family. http://togogenome.org/gene/10090:Gpr171 ^@ http://purl.uniprot.org/uniprot/Q8BG55 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice exhibit stronger antitumor immunity.|||G-protein coupled receptor for Big LEN, a 16-amino acid neuropeptide produced from the precursor protein, proSAAS (encoded by PCSK1N) (PubMed:24043826, PubMed:28425495). Acts through a G(i)-alpha-mediated pathway in response to Big LEN (PubMed:24043826). Big LEN-GPR171 system plays an important role in regulating feeding and metabolism (PubMed:24043826). Also plays a role in modulating fear and anxiety-like behaviors in the basolateral amygdala (PubMed:28425495). Big LEN-GPR171 modulates the mu-type opioid receptor signaling and antinociception (PubMed:31308196). Acts as a negative regulator T cell function (PubMed:34615877).|||Highly expressed in hypothalamus, including the arcuate nucleus, paraventricular nucleus and dorsomedial hypothalamus (PubMed:24043826). Expressed in periaqueductal gray (at protein level), found primarily in GABAergic neurons and to a lesser extent in glutamatergic neurons (PubMed:31308196). Expressed in T cells and natural killer cells (PubMed:34615877).|||Induced upon antigen stimulation. http://togogenome.org/gene/10090:Sema4g ^@ http://purl.uniprot.org/uniprot/Q9WUH7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Brain, spinal cord, and several sensory organs as well as specific populations of projection neurons.|||Cell membrane|||Cell surface receptor for PLXNB2. May play a role in axon guidance.|||Expressed early in development.|||Interacts with PLXNB2.|||No visible phenotype. http://togogenome.org/gene/10090:Commd3 ^@ http://purl.uniprot.org/uniprot/Q63829 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4A, CUL4B, CUL5.|||May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. May down-regulate activation of NF-kappa-B. Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits.|||Nucleus http://togogenome.org/gene/10090:Slco1a1 ^@ http://purl.uniprot.org/uniprot/Q53ZW9|||http://purl.uniprot.org/uniprot/Q9QXZ6 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Binds to PDZK1. Interaction with PDZK1 is required for expression on hepatocyte surface (By similarity).|||Cell membrane|||Highly expressed in liver, and at lower levels in kidney (PubMed:10600646, PubMed:11267661). Not detected in other tissues (PubMed:10600646).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the Na(+)-independent transport of organic anions such as steroid sulfate conjugates (dehydroepiandrosterone sulfate (DHEAS), 17-beta-glucuronosyl estradiol, estrone-3-sulfate), conjugated (taurocholate) and unconjugated (cholate) bile acids, prostaglandin E2 (PGE2) and L-thyroxine T4 (PubMed:10600646, PubMed:11267661). Also capable of transporting sulfobromophthalein (BSP), ouabain and gadoxetate (PubMed:10600646). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (By similarity). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (By similarity).|||Membrane http://togogenome.org/gene/10090:Them6 ^@ http://purl.uniprot.org/uniprot/Q80ZW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the THEM6 family.|||Secreted http://togogenome.org/gene/10090:Nat8f7 ^@ http://purl.uniprot.org/uniprot/E0CYR6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||Has histone acetyltransferase activity in vitro, with specificity for histone H4.|||Membrane http://togogenome.org/gene/10090:Rgcc ^@ http://purl.uniprot.org/uniprot/Q9DBX1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CDK1 and PLK1 (By similarity). Interacts with SMAD3.|||Modulates the activity of cell cycle-specific kinases. Enhances CDK1 activity. May contribute to the regulation of the cell cycle. May inhibit growth of glioma cells by promoting arrest of mitotic progression at the G2/M transition. Fibrogenic factor contributing to the pathogenesis of renal fibrosis through fibroblast activation.|||Nucleus|||centrosome http://togogenome.org/gene/10090:Ttc39a ^@ http://purl.uniprot.org/uniprot/A2ACP1 ^@ Similarity ^@ Belongs to the TTC39 family. http://togogenome.org/gene/10090:Sinhcaf ^@ http://purl.uniprot.org/uniprot/Q8C8M1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SINHCAF family.|||Component of the Sin3/HDAC corepressor complex at least composed of BRMS1, BRMS1L, ING2, SAP30, SAP30L, HDAC1 (By similarity). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with SIN3A and OGT (PubMed:28554894).|||Embryonic stem cells (at protein level).|||Nucleus|||Subunit of the Sin3 deacetylase complex (Sin3/HDAC), this subunit is important for the repression of genes encoding components of the TGF-beta signaling pathway (By similarity). Core component of a SIN3A complex (composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1) present in embryonic stem (ES) cells. Promotes the stability of SIN3A and its presence on chromatin and is essential for maintaining the potential of ES cells to proliferate rapidly, while ensuring a short G1-phase of the cell cycle, thereby preventing premature lineage priming (PubMed:28554894). http://togogenome.org/gene/10090:Mxra8 ^@ http://purl.uniprot.org/uniprot/Q9DBV4 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At embryonic stage 15.5 dpc, expressed in the growth plate of long bones where it is mostly found in chondrocytes in the resting and proliferative zones (at protein level) (PubMed:29702220). Expression gradually increases in differentiating osteoclasts, but then decreases during the late stages of differentiation (PubMed:22492581).|||Cell membrane|||Cytoplasm|||Disruption of the blood-brain barrier by cold injury results in a drastic reduction in expression (PubMed:14603461). Up-regulated in primary chondrocytes in response to BMP2 and PTHLH/PTHrP (PubMed:29702220).|||Homodimer in cis (PubMed:18366072). Does not appear to form trans-homodimers (PubMed:18366072). Interacts with ITGB3; the interaction inhibits ITGAV:ITGB3 heterodimer formation (PubMed:22492581).|||Nucleus|||RGD motif 2 (but not RGD motif 1) is involved in integrin ITGAV:ITGB3 binding.|||Transmembrane protein which can modulate activity of various signaling pathways, probably via binding to integrin ITGAV:ITGB3 (PubMed:18366072, PubMed:22492581, PubMed:29702220). Mediates heterophilic cell-cell interactions in vitro (PubMed:18366072). Inhibits osteoclastogenesis downstream of TNFSF11/RANKL and CSF1, where it may function by attenuating signaling via integrin ITGB3 and MAP kinase p38 (PubMed:22492581). Plays a role in cartilage formation where it promotes proliferation and maturation of growth plate chondrocytes (PubMed:29702220). Stimulates formation of primary cilia in chondrocytes (PubMed:29702220). Enhances expression of genes involved in the hedgehog signaling pathway in chondrocytes, including the hedgehog signaling molecule IHH; may also promote signaling via the PTHLH/PTHrP pathway (PubMed:29702220). Plays a role in angiogenesis where it suppresses migration of endothelial cells and also promotes their apoptosis (By similarity). Inhibits VEGF-induced activation of AKT and p38 MAP kinase in endothelial cells (By similarity). Also inhibits VTN (vitronectin)-mediated integrin ITGAV:ITGB3 signaling and activation of PTK2/FAK (By similarity). May play a role in the maturation and maintenance of the blood-brain barrier (PubMed:14603461).|||Widely expressed (at protein level) (PubMed:18366072). Highly expressed in brain where it localizes to the glia limitans, which is formed by the endfeet of astrocytes surrounding capillaries, and beneath the pia mater (at protein level) (PubMed:14603461). In lung, detected in epithelial cells of the bronchus (at protein level). Expressed in intercalated disks in the heart (at protein level) (PubMed:18366072). Detected in pancreatic alpha-cells in the islet of Langerhans (at protein level) (PubMed:18366072). In kidney, found in the brush border of the proximal convoluted tubule (at protein level) (PubMed:18366072). Expressed in the epithelium of the small intestine (at protein level) (PubMed:18366072). Weakly expressed in liver (at protein level) (PubMed:18366072). Detected in myeloid cells (PubMed:22492581).|||cilium membrane|||tight junction http://togogenome.org/gene/10090:Dnajc16 ^@ http://purl.uniprot.org/uniprot/Q80TN4 ^@ Function|||Subcellular Location Annotation ^@ Endoplasmic reticulum membrane|||Plays an important role in regulating the size of autophagosomes during the formation process. http://togogenome.org/gene/10090:Lexm ^@ http://purl.uniprot.org/uniprot/A2AVQ5 ^@ Caution ^@ Was reported to promote CD8+ T cell immunity through effects on mitochondrial respiration (PubMed:25883318). However, the corresponding article has been retracted (PubMed:27980177). http://togogenome.org/gene/10090:Rasa4 ^@ http://purl.uniprot.org/uniprot/Q6PFQ7 ^@ Cofactor|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 3 Ca(2+) ions per C2 domain.|||Ca(2+)-dependent Ras GTPase-activating protein, that switches off the Ras-MAPK pathway following a stimulus that elevates intracellular calcium. Functions as an adaptor for Cdc42 and Rac1 during FcR-mediated phagocytosis. Isoform 2 activates the Ras pathway and promotes RANKL shedding by modulating the expression of MMP14.|||Cell membrane|||Isoform 2 is expressed in osteoblasts.|||The PH domain does not bind phosphatidylinositol 4,5-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate. This lack of binding activity is due to Leu-591, compared to Arg found in other family members (By similarity).|||cytosol http://togogenome.org/gene/10090:Il1rap ^@ http://purl.uniprot.org/uniprot/E9Q6I2|||http://purl.uniprot.org/uniprot/Q3V2X3|||http://purl.uniprot.org/uniprot/Q61730 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with secreted ligand-bound IL1R2 and increases the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. Enhances the ability of secreted IL1R1 to inhibit IL-33 signaling.|||Belongs to the interleukin-1 receptor family.|||Cell membrane|||Coreceptor for IL1RL2 in the IL-36 signaling system. Coreceptor with IL1R1 in the IL-1 signaling system. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Secreted forms (isoforms 2 and 3) associate with secreted ligand-bound IL1R2 and increase the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors. Coreceptor for IL1RL1 in the IL-33 signaling system. Can bidirectionally induce pre- and postsynaptic differentiation of neurons by trans-synaptically binding to PTPRD (PubMed:25908590). May play a role in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells (By similarity).|||Detected in lung, brain, spleen, thymus and liver. Expressed in brain endothelial cells, astrocytes, microglia and neurons. Isoform 3 is predominantly expressed in brain; expressed in hippocampal neurons.|||Required for Src phosphorylation by IL1B. Required for IL1B-potentiated NMDA-induced calcium influx in neurons acting in cooperation with IL1R1 isoform 2 to mediate Akt kinase activation.|||Secreted|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.|||The interleukin-36 receptor complex is a heterodimer of IL1RL2 and IL1RAP; the association is inhibited by IL36RN. The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Associates with IL1R2 to form a non-signaling interleukin-1 receptor complex. Interacts with IL-33-bound IL1RL1 to form the minimal interleukin-33 signaling complex with a 1:1:1 stoichiometry. Interacts with KIT (independently of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88. Interacts (via the first immunoglobilin domain) with PTPRD (via the third immunoglobilin domain); induces pre- and postsynaptic differentiation of neurons (PubMed:25908590). http://togogenome.org/gene/10090:Foxa2 ^@ http://purl.uniprot.org/uniprot/G5E8P5|||http://purl.uniprot.org/uniprot/P35583 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA as a monomer. Binds TLE1 (By similarity). Interacts with FOXA1 and FOXA3 (By similarity). Interacts with PRKDC (By similarity). Interacts with AKT1 (PubMed:14500912). Interacts with TET1; this interaction may recruit TET1 to specific genomic loci to mediate their demethylation (By similarity).|||Cytoplasm|||Embryonic lethal; absence of organized node and notochord formation, which leads to secondary defects in dorsal-ventral patterning of the neural tube. Mice deficient for Fox1a and deficient for Foxa2 in the endoderm from 8.5 dpc onwards do not show hepatic bud formation. Mice deficient for Fox1a and deficient for Foxa2 in the midbrain from 10.5 dpc onwards show almost complete loss of mDA neurons. Mice deficient for Fox1a and deficient for Foxa2 in the embryonic liver show hyperplasia of the biliary tree due to at least in part activation of IL-6 expression, a proliferative signal for cholangiocytes. Mice deficient for Fox2a in pancreatic beta cell show hypoglycemia and disorganized islets arrangements.|||Most abundant in midgestation embryos (day 9.5).|||Nucleus|||Phosphorylation on Thr-156 abolishes binding to target promoters and subsequent transcription activation upon insulin stimulation.|||Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine). Expressed in epididymis with region-specific expression pattern: no expression is observed in initial segment, low expression in proximal caput, gradiently higher levels of expression in middle and distal caput and highest level in corpus and cauda (at protein level).|||Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; Foxa1 and Foxa2 seem to have at least in part redundant roles. FOXA1 and FOXA2 are essential for hepatic specification. FOXA1 and FOXA2 are required for morphogenesis and cell differentiation during formation of the lung. FOXA1 and FOXA2 are involved in bile duct formation; they positively regulate the binding glucocorticoid receptor/NR3C1 to the IL6 promoter. FOXA1 and FOXA2 regulate multiple phases of midbrain dopaminergic neuron development; they regulate expression of NEUROG2 at the beginning of mDA neurogenesis and of NR4A2 and EN1 in immature mDA neurons. Modulates the transcriptional activity of nuclear hormone receptors; inhibits AR-mediated transcription from the LCN5 promoter. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. In pancreatic beta cells activates transcription of potassium channel subunits KCNJ11 and ABCC8. Involved in regulation of fat metabolism; activates transcriptional programs of lipid metabolism and ketogenesis at low insulin state. Involved in transcriptional regulation of MUC2 in the intestine. http://togogenome.org/gene/10090:Trmt1 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZW7|||http://purl.uniprot.org/uniprot/E9PWD4|||http://purl.uniprot.org/uniprot/Q3TX08 ^@ Function|||Similarity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.|||Dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl-L-methionine as donor of the methyl groups. http://togogenome.org/gene/10090:Lrp5 ^@ http://purl.uniprot.org/uniprot/Q91VN0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins. Activates the canonical Wnt signaling pathway that controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration (PubMed:11956231). In particular, may play an important role in the development of the posterior patterning of the epiblast during gastrulation (PubMed:15142971). During bone development, regulates osteoblast proliferation and differentiation thus determining bone mass (PubMed:11956231). Mechanistically, the formation of the signaling complex between Wnt ligand, frizzled receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5, stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional programs (By similarity). Acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling known to be required for retinal vascular development (By similarity). Plays a role in controlling postnatal vascular regression in retina via macrophage-induced endothelial cell apoptosis (PubMed:11956231).|||Belongs to the LDLR family.|||Endoplasmic reticulum|||Expressed in early embryo throughout the ectoderm at 6.5 dpc and in visceral endoderm overlying the extraembryonic ectoderm at 7.5 dpc. Not present in the mesoderm nor in endoderm emerging from the primitive streak (PubMed:15142971). Expressed in differentiating osteoblasts that contribute to the lateral membranous part of clavicle at embryonic day 13.5. Expressed in osteoblasts lining the bony trabeculae of the humerus at embryonic day 16.5. Expressed in osteoblasts on both surfaces of the temporal bone at embryonic day 17.5 (PubMed:11719191).|||Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling (PubMed:12581525). Component of a WNT-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts with FZD8; the interaction is formed on WNT-binding and signaling. Interacts (via the phosphorylated PPPSP motif domains) with AXIN1; the interaction prevents inhibition of beta-catenin phosphorylation and signaling and is enhanced in the presence of GSK3B and WNT1 or WNT3A. Interacts (via beta-propeller regions 3 and 4) with DKK1; the interaction, enhanced by MESD and/or KREMEN, inhibits beta-catenin signaling by preventing GSK3-mediated phosphorylation of the PPPSP motifs and subsequent, AXIN1 binding. Interacts with CSNK1E. Interacts with SOST; the interaction antagonizes canonical Wnt signaling. Interacts with APCDD1 (By similarity). Interacts with MESD; the interaction prevents the formation of LRP5 aggregates, targets LRP5 to the plasma membrane and, when complexed with KREMEN2, increases DKK1 binding (PubMed:12581525). Interacts with CAPRIN2 (By similarity).|||Membrane|||Mice exhibit decreased osteoblast proliferation, developing low bone mass postnatally. Also display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. Mutant animals exhibit a loss of middle phalanx ossification at 18.5 dpc. LRP5 and LRP6 double null mutants are more severely affected. Embryos arrest prior to mid-gestation.|||Phosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1.|||Widely expressed, with the highest expression levels in liver, heart, and lung and the lowest levels in brain and spleen. http://togogenome.org/gene/10090:Mcpt1 ^@ http://purl.uniprot.org/uniprot/P11034 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytoplasmic granule|||Has a chymotrypsin-like activity.|||Mucosal mast cells.|||Secreted http://togogenome.org/gene/10090:Or6c205 ^@ http://purl.uniprot.org/uniprot/Q7TRI4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cpeb4 ^@ http://purl.uniprot.org/uniprot/Q5SU48|||http://purl.uniprot.org/uniprot/Q7TN98 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM CPEB family.|||Cytoplasm|||Endoplasmic reticulum|||Highly expressed in brain, including hippocampus, amygdala, granule and Purkinje cells of the cerebellum (at protein level) (PubMed:17024188, PubMed:24386439). Expressed in spinal cord (at protein level) (PubMed:27381259). Expressed in kidney, lung and heart (at protein level) (PubMed:12871996, PubMed:27381259, PubMed:24386439). Expressed in liver (at protein level) (PubMed:28092655, PubMed:12871996, PubMed:27381259, PubMed:24386439). Expressed in spleen and testis (at protein level) (PubMed:24386439, PubMed:12871996). Weakly expressed in ovary and in granular cells of dentate gyrus and the pyramidal cells of CA3 and CA1 of the hippocampus (PubMed:12871996).|||Highly expressed in developing brain, spinal cord and attached dorsal root ganglia (DRG) (at protein level). At embryonic day 18.5 expressed in gray matter of spinal cord, diencephalons, hippocampus and parts of midbrain and hindbrain. At postnatal day 20 expression persists in spinal cord and brain. Expressed in embryonic heart.|||Interacts with TOB1.|||No visible phenotype at young age or under unchallenged conditions (PubMed:24386439, PubMed:28092655). At 80 weeks or under high fat diet feeding conditions, mutant mice develop hepatosteatosis with excessive liver weight and accumulation of cytosolic lipid droplets sometimes accompanied by fibrosis (PubMed:28092655).|||Postsynaptic density|||Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR (PubMed:17024188). RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism (By similarity). Regulates activation of unfolded protein response (UPR) in the process of adaptation to ER stress in liver, by maintaining translation of CPE-regulated mRNAs in conditions in which global protein synthesis is inhibited (PubMed:28092655). Required for cell cycle progression, specifically for cytokinesis and chromosomal segregation (By similarity). Plays a role as an oncogene promoting tumor growth and progression by positively regulating translation of t-plasminogen activator/PLAT (PubMed:22138752). Stimulates proliferation of melanocytes (By similarity). In contrast to CPEB1 and CPEB3, does not play role in synaptic plasticity, learning and memory (PubMed:24386439).|||The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA. The interdomain linker (564-579) acts as a hinge to fix the relative orientation of the 2 RRMs. The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs. Unlike in CPEB1, a continuous polar interface is formed between the 2 RRMs.|||Up-regulated in granular cells of the dentate gyrus of CA1 and CA3 after kainate-induced seizures (PubMed:12871996). Up-regulated by high-fat-diet and aging-induced endoplasmic reticulum stress (PubMed:28092655). Expression level fluctuation follows the circadian clock amplitude (PubMed:28092655).|||axon|||dendrite|||dendritic spine|||growth cone|||perinuclear region http://togogenome.org/gene/10090:Pim1 ^@ http://purl.uniprot.org/uniprot/P06803 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated on both serine/threonine and tyrosine residues. Phosphorylated. Interaction with PPP2CA promotes dephosphorylation (By similarity).|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.|||Cell membrane|||Cytoplasm|||Deficient mice are viable and fertile however they have a specific defect in interleukin-7 (IL7)-driven growth of pre-B cells, as well as IL3-dependent growth of bone marrow-derived mast cells. Triple knockout mice PIM1/PIM2/PIM3 are viable and fertile too, but their body size is reduced at birth and throughout postnatal life due to a reduction in the number of cells rather than cell size.|||Frequently activated by provirus insertion in murine leukemia virus-induced T-cell lymphomas.|||Initiates from CTG codon.|||Interacts with RP9 (PubMed:10931201). Interacts with HSP90AA1, this interaction stabilizes PIM1 protein levels. Interacts (ubiquitinated form) with HSP70 and promotes its proteasomal degradation (By similarity).|||Isoform 1 is isolated as a monomer whereas isoform 2 complexes with other proteins.|||Nucleus|||Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis (PubMed:15199164, PubMed:1825810). Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3) (By similarity). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity (PubMed:18438430). The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis (PubMed:18438430). Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1 (PubMed:15280015). Phosphorylation of MAP3K5, another proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis (By similarity). Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C (By similarity). Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability (By similarity). Promotes cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels (By similarity). Phosphorylation of CDKN1B, induces 14-3-3 proteins binding, nuclear export and proteasome-dependent degradation (By similarity). May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3 (By similarity). Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis (PubMed:19687226). Acts as a positive regulator of mTORC1 signaling by mediating phosphorylation and inhibition of DEPDC5 component of the GATOR1 complex (PubMed:31548394). Also phosphorylates and activates the ATP-binding cassette transporter ABCG2, allowing resistance to drugs through their excretion from cells (By similarity). Promotes brown adipocyte differentiation (PubMed:27923061).|||Ubiquitinated, leading to proteasomal degradation. http://togogenome.org/gene/10090:Cd36 ^@ http://purl.uniprot.org/uniprot/Q08857|||http://purl.uniprot.org/uniprot/Q3U6Y9|||http://purl.uniprot.org/uniprot/Q3UAI3|||http://purl.uniprot.org/uniprot/Q3UC79|||http://purl.uniprot.org/uniprot/Q8C6Z4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Acts as an accessory receptor for M.tuberculosis lipoprotein LprA, in conjunction with coreceptors TLR2 and TLR1; the lipoprotein acts as an agonist to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling (PubMed:19864601, PubMed:23395392). Mediates uptake of E.coli and S.aureus but has no effect on uptake of M.fortuitum (PubMed:16020694).|||Apical cell membrane|||Belongs to the CD36 family.|||Cell membrane|||Expressed in a circadian manner in the circumvallate papillae, levels being lower during the dark period. Protein levels decrease in presence of lipids.|||Expressed in the apical side of lingual taste bud cells of the circumvallate papillae (PubMed:16276419, PubMed:21901153). Highly expressed in the intestine on the luminal surface of enterocytes. In small intestines expression levels follow a steep decreasing gradient from proximal to distal segments (PubMed:17507371). Expressed in macrophages (PubMed:23395392, PubMed:23812099). Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and lung macrophages (at protein level) (PubMed:19362712).|||Golgi apparatus|||Interacts with THBS1 and THBS2; the interactions mediate the THBS antiangiogenic activity (By similarity) (PubMed:15748999). Upon interaction with a ligand, such as oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42, rapidly forms a complex with TLR4 and TLR6; the complex is internalized and triggers an inflammatory signal. Through its C-terminus, interacts with PTK2, PXN and LYN, but not with SRC. LYN kinase activity is required for facilitating TLR4-TLR6 heterodimerization and signal initiation (By similarity). Interacts with CD9, CD81, FCER1G, ITGB2 and/or ITGB2; forming a membrane heteromeric complex required for the internalization of CD36 and its ligands (PubMed:23395392).|||Membrane raft|||Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides (PubMed:7685021). They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (Probable) (PubMed:19847289, PubMed:20037584, PubMed:23395392). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (PubMed:30605677). Mechanistically, binding of fatty acids activates downstream kinase LYN, which phosphorylates the palmitoyltransferase ZDHHC5 and inactivates it, resulting in the subsequent depalmitoylation of CD36 and caveolar endocytosis (By similarity). In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway (By similarity) (PubMed:17507371, PubMed:18753675, PubMed:21610069). Involved in oral fat perception and preferences (PubMed:16276419). Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions (By similarity) (PubMed:16276419). In taste receptor cells, mediates the induction of an increase in intracellular calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (PubMed:18162488). Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis (By similarity) (PubMed:23557700). Receptor for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (PubMed:15748999). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting together with THBS1 (PubMed:25835637). As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome (PubMed:20037584, PubMed:23812099). Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (By similarity) (PubMed:15690042, PubMed:19847289).|||Palmitoylated by ZDHHC5. Palmitoylation is required for proper localization at the plasma membrane.|||The preference to lipids such linoleic acid is fully abolished in mutant mice as well as the induction of both flux and protein content of pancreatobiliary secretions (PubMed:21901153, PubMed:16276419). Animals with a double knockout of APOE and CD36, fed a Western diet for 12 weeks, exhibit much lower levels of CXCL1, CXCL2 and CCL5 cytokine mRNA expression in the descending aorta and a corresponding decrease in atherosclerotic lesion formation, compared to APOE single knockout mice. Enterocytes from proximal small intestine exhibit reduced uptake of fatty acid and cholesterol. They also show reduced fatty acid incorporation into triglycerides and triglyceride secretion (PubMed:17507371). After oral fat loading, animals have lipoproteins smaller than chylomicron in size in plasma and intestinal lymph (PubMed:18753675). Fewer apoptotic cells and reduced levels of active caspase 3 in glomeruli.|||Ubiquitinated at Lys-469 and Lys-472. Ubiquitination is induced by fatty acids such as oleic acid and leads to degradation by the proteasome (PubMed:21610069, PubMed:18353783). Ubiquitination and degradation are inhibited by insulin which blocks the effect of fatty acids (PubMed:18353783). http://togogenome.org/gene/10090:Dbndd1 ^@ http://purl.uniprot.org/uniprot/H3BK17|||http://purl.uniprot.org/uniprot/H3BKU0|||http://purl.uniprot.org/uniprot/Q9CZ00 ^@ Similarity ^@ Belongs to the dysbindin family. http://togogenome.org/gene/10090:Gata2 ^@ http://purl.uniprot.org/uniprot/O09100|||http://purl.uniprot.org/uniprot/Q3U320 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Interacts with BRD3. Interacts with AR and CCAR1 (By similarity). Interacts with MDFIC (PubMed:35235341).|||Nucleus|||Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'-AGATAG-3'. http://togogenome.org/gene/10090:Csn3 ^@ http://purl.uniprot.org/uniprot/P06796 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the kappa-casein family.|||Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk.|||Mammary gland specific. Secreted in milk.|||Secreted http://togogenome.org/gene/10090:Cdh18 ^@ http://purl.uniprot.org/uniprot/E9Q9Q6 ^@ Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Myb ^@ http://purl.uniprot.org/uniprot/A0A087WPA7|||http://purl.uniprot.org/uniprot/P06876 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds to HIPK1 (By similarity). Interacts with HIPK2, MAF, MYBBP1A and NLK.|||C-terminal truncated mutants display increased transactivation.|||Comprised of 3 domains; an N-terminal DNA-binding domain, a centrally located transcriptional activation domain and a C-terminal domain involved in transcriptional repression.|||Nucleus|||Phosphorylated by HIPK1. This phosphorylation reduces MYB transcription factor activity but not MYB protein levels (By similarity).|||Phosphorylated by NLK on multiple sites, which induces proteasomal degradation.|||SUMOylated by TRAF7; leading to MYB transcriptional activity inhibition.|||Transcriptional activator; DNA-binding protein that specifically recognize the sequence 5'-YAAC[GT]G-3'. Plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells.|||Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Cyp4b1 ^@ http://purl.uniprot.org/uniprot/Q3TNA0|||http://purl.uniprot.org/uniprot/Q64462 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane|||P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.|||Present abundantly in renal microsomes of male mice but not in those of female mice. Also present in pulmonary microsomes of male and female mice. Not found in liver.|||Responsible for mutagenic activation of 3-methoxy-4-aminoazobenzene (3-MeO-AAB); a potent procarcinogen. Also active on 2-aminofluorene and 2-aminoanthracene. http://togogenome.org/gene/10090:Or2at4 ^@ http://purl.uniprot.org/uniprot/E9Q518 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rpl7l1 ^@ http://purl.uniprot.org/uniprot/Q9D8M4 ^@ Similarity ^@ Belongs to the universal ribosomal protein uL30 family. http://togogenome.org/gene/10090:Nfil3 ^@ http://purl.uniprot.org/uniprot/O08750 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator that recognizes and binds to the sequence 5'-[GA]TTA[CT]GTAA[CT]-3', a sequence present in many cellular and viral promoters. Represses transcription from promoters with activating transcription factor (ATF) sites (By similarity). Represses promoter activity in osteoblasts. Represses transcriptional activity of PER1. Represses transcriptional activity of PER2 via the B-site on the promoter. Activates transcription from the interleukin-3 promoter in T-cells (By similarity). Competes for the same consensus-binding site with PAR DNA-binding factors (DBP, HLF and TEF). Component of the circadian clock that acts as a negative regulator for the circadian expression of PER2 oscillation in the cell-autonomous core clock. Protects pro-B cells from programmed cell death. Represses the transcription of CYP2A5 (PubMed:30555544). Positively regulates the expression and activity of CES2 by antagonizing the repressive action of NR1D1 on CES2 (PubMed:29653076). Required for the development of natural killer cell precursors (PubMed:32190943).|||Belongs to the bZIP family. NFIL3 subfamily.|||Expressed in suprachiasmatic nucleus and liver (at protein level). Expressed in suprachiasmatic nucleus, hippocampus, gyrus dentatus, piriform cortex, internal granular layer of olfactory bulb, dorsomedial hypothalamic nucleus, pontine nuclei, granular layer of cerebellum, liver and calvariae osteoblasts. Expressed in natural killer cell precursors in bone marrow (PubMed:32190943).|||Expression is regulated by circadian rhythms. Up-regulated by parathyroid hormone (PTH) (at protein level). Up-regulated by IL-3, forskolin, 8-bromo-cAMP, phorbol myristate acetate and PTH in primary osteoblasts and calvariae.|||Homodimer (By similarity). Binds DNA as a dimer (By similarity). Interacts with DR1 (By similarity). Interacts with PER2 and CRY2 (PubMed:17274955). Interacts with NR0B2 (PubMed:30555544). Interacts with NR1D1 (PubMed:29653076). Interacts with MYSM1 (By similarity).|||Nucleus|||Reduced number of natural killer cell-committed progenitors in bone marrow. http://togogenome.org/gene/10090:Myo16 ^@ http://purl.uniprot.org/uniprot/Q5DU14 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At postnatal day 1, highly expressed in upper neocortex and also detected in the olfactory bulb, but not in the striatum.|||Binds PPP1CA and/or PPP1CC. Binds F-actin in an ATP-sensitive manner (By similarity). Interacts with ACOT9, ARHGAP26 and PIK3R2. Interacts with components of the WAVE1 complex, CYFIP1 and NCKAP1; this interaction mediates PI3K-WAVE1 association and actin cytoskeleton remodeling (PubMed:21946561). Interacts with KIRREL3 (By similarity).|||Cytoplasm|||Expressed predominantly in brain where it is present in the neurons, but not in astrocytes or oligodendrites.|||In the C-terminal section; belongs to the NYAP family.|||In the N-terminal section; belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. May be involved in targeting of the catalytic subunit of protein phosphatase 1 during brain development (By similarity). Activates PI3K and concomitantly recruits the WAVE1 complex to the close vicinity of PI3K and regulates neuronal morphogenesis.|||Phosphorylated on tyrosine residues by FYN upon stimulation with CNTN5. Phosphorylation begins at 14 dpc, reaches a peak during perinatal days in brain, then gradually decreases.|||Triple knockout mice NYAP1/NYAP2/MYO16 are fertile and appear healthy. However, compared to wild-type mice they show a clear reduction in brain size, exhibiting a reduction in the size of the cortex and striatum, but not the olfactory bulb or corpus callosum. The total neurite length of neurons in these mice is also significantly shorter. http://togogenome.org/gene/10090:Clybl ^@ http://purl.uniprot.org/uniprot/Q8R4N0 ^@ Caution|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HpcH/HpaI aldolase family. Citrate lyase beta subunit-like subfamily.|||Binds 1 Mg(2+) ion per subunit.|||Detected in brown fat, brain, liver, kidney, heart, skeletal muscle and ovary (at protein level).|||Homotrimer.|||Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (By similarity). The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (By similarity). Also displays malyl-CoA thioesterase activity. Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (By similarity). Also has very weak citramalate synthase activity in vitro (By similarity).|||Mitochondrion|||This organism lacks the other subunits that are necessary for ATP-independent citrate lyase activity. Even though this protein has clear similarity to citrate lyase beta subunit, it is expected to have a somewhat different enzyme activity. http://togogenome.org/gene/10090:Or5p1 ^@ http://purl.uniprot.org/uniprot/Q8VG06 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Fibin ^@ http://purl.uniprot.org/uniprot/Q9CQS3 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 9.5 dpc and 10.5 dpc, abundantly expressed in the forelimb buds.|||Belongs to the FIBIN family.|||Endoplasmic reticulum|||Golgi apparatus|||Homodimer; disulfide-linked. Seems to also exist as monomers (By similarity).|||Secreted http://togogenome.org/gene/10090:Qsox2 ^@ http://purl.uniprot.org/uniprot/Q3TMX7 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the quiescin-sulfhydryl oxidase (QSOX) family.|||Binds 1 FAD per subunit.|||Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide. May contribute to disulfide bond formation in a variety of secreted proteins (By similarity).|||Membrane http://togogenome.org/gene/10090:Psmd1 ^@ http://purl.uniprot.org/uniprot/Q3TXS7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the proteasome subunit S1 family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD1. Interacts with ADRM1. Interacts with ZFAND1 (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. http://togogenome.org/gene/10090:Pacsin3 ^@ http://purl.uniprot.org/uniprot/Q99JB8 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PACSIN family.|||Cell membrane|||Cytoplasm|||Highly expressed in skeletal muscle, heart and lung; also detected in brain, kidney and uterus (at protein level).|||Homodimer. May form heterooligomers with other PACSINs. Interacts (via SH3 domain) with DNM1, SYNJ1 and WASL. Interacts with TRPV4.|||Phosphorylated by casein kinase 2 (CK2) and protein kinase C (PKC).|||Plays a role in endocytosis and regulates internalization of plasma membrane proteins. Overexpression impairs internalization of SLC2A1/GLUT1 and TRPV4 and increases the levels of SLC2A1/GLUT1 and TRPV4 at the cell membrane. Inhibits the TRPV4 calcium channel activity.|||The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. http://togogenome.org/gene/10090:Or10ak11 ^@ http://purl.uniprot.org/uniprot/Q7TQV7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Pheta1 ^@ http://purl.uniprot.org/uniprot/Q8BH49 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sesquipedalian family.|||Early endosome|||Forms homodimers and heterodimers with PHETA2. Interacts with OCRL and INPP5B (By similarity). Interaction with OCRL may be important for endosomal morphology and function (By similarity).|||Plays a role in endocytic trafficking. Required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane.|||Recycling endosome|||The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B.|||Was named after 'sesquipedalian', an unnecessarily long description of a simple thing.|||clathrin-coated vesicle|||trans-Golgi network http://togogenome.org/gene/10090:Rimbp2 ^@ http://purl.uniprot.org/uniprot/A0A0G2JFB0|||http://purl.uniprot.org/uniprot/D3YXR8|||http://purl.uniprot.org/uniprot/Q80U40 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RIMBP family.|||Cell membrane|||Interacts with RIMS1, RIMS2, CACNA1D and CACNA1B, and potentially with other Ca(2+) channel alpha-1 isoforms.|||Plays a role in the synaptic transmission as bifunctional linker that interacts simultaneously with RIMS1, RIMS2, CACNA1D and CACNA1B.|||Synapse|||The SH3 domains mediate binding to a proline-rich motif in RIMS1, RIMS2, CACNA1D and CACNA1B. http://togogenome.org/gene/10090:Icam4 ^@ http://purl.uniprot.org/uniprot/Q14AB0|||http://purl.uniprot.org/uniprot/Q9ERM2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Adhesion molecule that binds to leukocyte adhesion LFA-1 protein LFA-1 (integrin alpha-L/beta-2). ICAM4 is also a ligand for alpha-4/beta-1 and alpha-V integrins (By similarity). Isoform 2 may modulate binding of membrane-associated ICAM4.|||Belongs to the immunoglobulin superfamily. ICAM family.|||Cell membrane|||Membrane|||Secreted http://togogenome.org/gene/10090:Nuak1 ^@ http://purl.uniprot.org/uniprot/Q641K5 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation on Thr-212. Activated by phosphorylation at Ser-601 AKT1 during glucose starvation; the relevance of such activation in normal cells is however unsure (By similarity).|||At 7.5 dpc, expressed in allantois and anterior visceral endoderm. In the embryonic part, present in mesoderm migrating laterally but not in the primitive streak; the expression is not apparent in ectoderm or endoderm at this stage. At 8.5 dpc, no expression is found in mesodermal tissues, while it is expressed in midbrain and isthmic regions of the neuroectoderm; it is also found in the pharyngeal region of the foregut. At 9.5 dpc, the expression is found throughout the undifferentiated neuroectoderm, except the telencephalic region. The expression is also ubiquitous in the epidermis; it is especially apparent in the ventral body wall. Also expressed in dorsal root ganglia of neural crest origin. The expression persists in the anterior gut and is also found in bulb arteriosus, kidney, and several connective tissues. At 12.5 dpc, the expression is greatly reduced in most of the neuroectoderm, but some expression remains in pons, anterior tectum, tegmentum, pretectum, prethalamus, mammillary region and hypothalamus. In telencephalon, expression is present in the differentiating preplate of the cortex. The expression is sustained in the epidermis of the whole body. In 14.5 and 18.5 dpc brain, expressed in differentiated fields of the cortex; no significant expression is found in other parts of brain or in the spinal cord. The expression is also present in a variety of connective tissues and in the epidermis of the whole body.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.|||Cytoplasm|||Expressed in the developing central nervous system, in epidermis, and some other tissues.|||Interacts (via GILK motif) with PPP1CB; the interaction is direct and bridges NUAK1 and PPP1R12A. Interacts with CDKN1A.|||Lethal during development, no live-born. At 18.5 dpc, homozygous mutants suffer from omphalocele with a failure in closure of the secondary body wall leading to organs outside of the abdomen. Omphalocele are apparent at 14.5 dpc when the physiological hernia is almost rectified in wild-type embryos.|||Nucleus|||Phosphorylated at Thr-212 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not dephosphorylated by the myosin PP1 complex when regulating its activity, due to the presence of PPP1R12A, which prevents myosin PP1 from dephosphorylating NUAK1. Phosphorylated by STK38L upon stimulation with IGF1 (By similarity).|||Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair.|||The GILK motif mediates interaction with PPP1CB.|||Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X (By similarity). http://togogenome.org/gene/10090:Capn7 ^@ http://purl.uniprot.org/uniprot/Q9R1S8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C2 family.|||Calcium-regulated non-lysosomal thiol-protease.|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Zfp263 ^@ http://purl.uniprot.org/uniprot/Q8CF60 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ An isoform of Znf263 lacking residues 1-288 was described, however this paper was retracted due to concerns about the validity of figures published in the paper.|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed in Purkinje cells in the brain (at protein level).|||Interacts with a number of proteins involved in chromatin modification and transcriptional corepression including DNMT1, DNMT3A, HDAC2, PHF8, TRIM28/KAP1, SETDB1, EZH2, UHRF1, CBX3/HP1-gamma, and CBX5/HP1-alpha; recruits these proteins to the SIX3 promoter region, leading to SIX3 transcriptional repression (By similarity). Interacts with MAPK3/ERK1 and MAPK1/ERK2 (By similarity).|||Nucleus|||Transcription factor that binds to the consensus sequence 5'-TCCTCCC-3' and acts as a transcriptional repressor (By similarity). Binds to the promoter region of SIX3 and recruits other proteins involved in chromatin modification and transcriptional corepression, resulting in methylation of the promoter and transcriptional repression (By similarity). Acts as transcriptional repressor of HS3ST1 and HS3ST3A1 via binding to gene promoter regions (By similarity).|||Ubiquitinated, leading to proteasomal degradation. http://togogenome.org/gene/10090:Eya2 ^@ http://purl.uniprot.org/uniprot/O08575|||http://purl.uniprot.org/uniprot/Q3UR62|||http://purl.uniprot.org/uniprot/Q3UV00 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HAD-like hydrolase superfamily. EYA family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Extensively expressed in cranial placodes, branchial arches, CNS and developing eye and nose. Low expression in lung with little or no expression in skin, liver, intestine and kidney. Predominantly expressed in the upper one-third of the oxyntic mucosa and in most regions of the pyloric mucosa.|||Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:10490620, PubMed:17098221). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis (By similarity). Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1 (By similarity).|||No visible phenotype. In contrast, mice lacking both Eya1 and Eya2 display complete embryonic lethality, due to severe defects in muscle development, including the absence of the diaphragm, the absence of ventral hypaxial muscles of the trunk and muscles in forelimbs and hindlimbs, similar to the phenotype of mice lacking both Six1 and Six4. While Six1 is normally expressed in these mice, it does not activate transcription from cognate promoter elements, and does not activate transcription of Pax3.|||Nucleus|||Probably interacts with SIX2, SIX4 and SIX5. Interacts with DACH2. Interacts with GNAZ and GNAI2; this retains EYA2 in the cytoplasm and prevents its translocation into the nucleus and transcriptional activity (By similarity). Interacts with SIX1. Interacts with CAPN8. http://togogenome.org/gene/10090:Abcf3 ^@ http://purl.uniprot.org/uniprot/Q8K268 ^@ Caution|||Function|||Similarity ^@ Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.|||Displays an antiviral effect against flaviviruses such as west Nile virus (WNV) in the presence of OAS1B.|||Lacks transmembrane domains and is probably not involved in transport. http://togogenome.org/gene/10090:G6pc3 ^@ http://purl.uniprot.org/uniprot/Q6NSQ9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glucose-6-phosphatase family.|||Endoplasmic reticulum membrane|||Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function.|||Inhibited by vanadate.|||Mice display reduced glucose-6-phosphate hydrolytic activity in the brain. No phenotypic difference was noted at birth but 4 months old female mice display growth retardation. Mutant mice exhibit a decreased plasma cholesterol concentration and an increased plasma glucagon concentration but no difference in blood glucose concentration (PubMed:17023421). Mice display neutropenia and neutrophil dysfunctions.|||Widely expressed. Highly expressed in heart and testis and to a lower extent in spleen, stomach, small intestine, skeletal muscle and uterus. Expressed in muscle, brain, thymus, lung, kidney, spleen and pancreas (at protein level). In the brain, expressed in astrocytes (at protein level) (PubMed:15661744). http://togogenome.org/gene/10090:Ly6d ^@ http://purl.uniprot.org/uniprot/P35459 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Lymphoid cells lacking Ly6d, called ALP (all-lymphoid progenitor), retain full lymphoid potential and early thymic seeding activity, whereas cells containing Ly6d, called BLP (B-cell-biased lymphoid progenitor), up-regulate the B-cell specifying factors Ebf1 and Pax5 and behave essentially as B-cell progenitors (at protein level). Thymocytes and B-cells.|||May act as a specification marker at earliest stage specification of lymphocytes between B- and T-cell development. Marks the earliest stage of B-cell specification. http://togogenome.org/gene/10090:C1qtnf7 ^@ http://purl.uniprot.org/uniprot/Q8BVD7 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Dusp21 ^@ http://purl.uniprot.org/uniprot/Q9D9D8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with preference for the phosphotyrosine and diphosphorylated forms over phosphothreonine.|||Cytoplasm|||Mitochondrion inner membrane|||Nucleus|||Selectively expressed in testis. http://togogenome.org/gene/10090:Cyp2r1 ^@ http://purl.uniprot.org/uniprot/Q32MW1|||http://purl.uniprot.org/uniprot/Q6VVW9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in activation of vitamin D precursors (PubMed:12867411, PubMed:24019477). Catalyzes hydroxylation at C-25 of both forms of vitamin D, vitamin D(2) and D(3) (calciol). Can metabolize vitamin D analogs/prodrugs 1alpha-hydroxyvitamin D(2) (doxercalciferol) and 1alpha-hydroxyvitamin D(3) (alfacalcidol) forming 25-hydroxy derivatives. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:12867411, PubMed:24019477) (By similarity).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highly expressed in the liver and testis.|||Homodimer.|||Microsome membrane|||Mutant mice are born at the expected Mendelian rate and have normal development. They display substantial reduction of serum calcidiol levels. http://togogenome.org/gene/10090:Sncaip ^@ http://purl.uniprot.org/uniprot/Q99ME3 ^@ PTM|||Subunit ^@ Associates with SNCA, RNF19A and PRKN.|||Ubiquitinated; mediated by SIAH1 or RNF19A and leading to its subsequent proteasomal degradation. http://togogenome.org/gene/10090:Tbc1d7 ^@ http://purl.uniprot.org/uniprot/Q9D0K0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the TSC-TBC complex (also named Rhebulator complex), composed of 2 molecules of TSC1, 2 molecules of TSC2 and 1 molecule of TBC1D7 (PubMed:22795129). Interacts with TSC1 (via C-terminal half of the coiled-coil domain) (By similarity).|||Cytoplasmic vesicle|||Lysosome membrane|||Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:22795129). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (By similarity). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (By similarity). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (By similarity).|||cytosol http://togogenome.org/gene/10090:Tcte1 ^@ http://purl.uniprot.org/uniprot/A6H639 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DRC5 family.|||Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. May play a role in the assembly of N-DRC (By similarity). Required for sperm motility (PubMed:28630322).|||Component of the nexin-dynein regulatory complex (N-DRC). Interacts with DRC1 (By similarity). Interacts with FBXL13/DRC6, DRC3 and DRC7 (PubMed:28630322, PubMed:31961863).|||Male mice are sterile due to asthenozoospermia (sperm with diminished progressive motility) and the diminished motility is due to aberrant flagellar function, with sperm tails contracting toward one side and generating a circular path for sperm.|||Testis-specific (at protein level).|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Tom1l1 ^@ http://purl.uniprot.org/uniprot/Q8BZR6 ^@ Similarity ^@ Belongs to the TOM1 family. http://togogenome.org/gene/10090:Tmem150a ^@ http://purl.uniprot.org/uniprot/Q91WN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DRAM/TMEM150 family.|||Cell membrane|||Interacts (via C-terminal cytoplasmic tail) with PI4KA.|||Regulates localization of phosphatidylinositol 4-kinase (PI4K) to the plasma membrane, possibly by reducing the association of TTC7 (TTC7A or TTC7B) with the PI4K complex. Acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (By similarity). May also play a role in fasting-induced catabolism (By similarity). http://togogenome.org/gene/10090:Rhoa ^@ http://purl.uniprot.org/uniprot/Q9QUI0 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Cleavage furrow|||Cytoplasm|||Interacts with ARHGEF28 (PubMed:11058585). Interacts (via GTP-bound form) with RIPOR1 (via N-terminus); this interaction links RHOA to STK24 and STK26 kinases. Interacts with RIPOR2 (via active GTP- or inactive GDP-bound forms) isoform 1 and isoform 2; these interactions are direct, block the loading of GTP to RHOA and decrease upon chemokine CCL19 stimulation in primary T lymphocytes. Binds PRKCL1, ROCK1 and ROCK2 (By similarity). Interacts with ARHGEF2, ARHGEF3, NET1 and RTKN (PubMed:9535835, PubMed:8662891). Interacts with PLCE1 and AKAP13 (By similarity). Interacts with DIAPH1 (PubMed:9214622). Interacts (in the constitutively activated, GTP-bound form) with DGKQ. Interacts with RACK1; enhances RHOA activation. Interacts with PKP4; the interaction is detected at the midbody (By similarity). Interacts (GTP-bound form preferentially) with PKN2; the interaction stimulates autophosphorylation and phosphorylation of PKN2 (PubMed:20974804). Interacts with ARHGDIA; this interaction inactivates and stabilizes RHOA. Interacts with ARHGDIB (By similarity). Interacts (GTP-bound form) with KCNA2 (via cytoplasmic N-terminal domain) (PubMed:9635436). Interacts (GTP-bound form) with ECT2; the interaction results in allosteric activation of ECT2 (By similarity). Interacts with RAP1GDS1; the interaction is direct and in a 1:1 stoichiometry (By similarity).|||Midbody|||Nucleus|||Phosphorylation by PRKG1 at Ser-188 inactivates RHOA signaling (By similarity). Phosphorylation by SLK at Ser-188 in response to AGTR2 activation (By similarity).|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Activated by GEFs such as ARHGEF2, ARHGEF3, ARHGEF28 and BCR. Inhibited by GAPs such as ARHGAP30. Inhibited by GDP dissociation inhibitors such as ARHGDIA.|||Serotonylation of Gln-63 by TGM2 during activation and aggregation of platelets leads to constitutive activation of GTPase activity.|||Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:14697203). Mainly associated with cytoskeleton organization, in active state binds to a variety of effector proteins to regulate cellular responses such as cytoskeletal dynamics, cell migration and cell cycle. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis (By similarity). Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion (PubMed:11777936, PubMed:20974804). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis. Acts as an allosteric activator of guanine nucleotide exchange factor ECT2 by binding in its activated GTP-bound form to the PH domain of ECT2 which stimulates the release of PH inhibition and promotes the binding of substrate RHOA to the ECT2 catalytic center (By similarity). May be an activator of PLCE1 (PubMed:9635436). In neurons, involved in the inhibition of the initial spine growth. Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (PubMed:14697203).|||Ubiquitinated by the BCR(KCTD13) and BCR(TNFAIP1) E3 ubiquitin ligase complexes, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and synaptic transmission in neurons. Ubiquitinated at Lys-135 in a FBXL19-mediated manner; leading to proteasomal degradation (By similarity).|||Up-regulated during keratinocyte differentiation.|||cell cortex|||cytoskeleton|||dendrite|||lamellipodium http://togogenome.org/gene/10090:Cdh7 ^@ http://purl.uniprot.org/uniprot/Q8BM92 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types (By similarity).|||Cell membrane|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. http://togogenome.org/gene/10090:Babam1 ^@ http://purl.uniprot.org/uniprot/Q3UI43 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BABAM1 family.|||Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1 and BABAM2. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex.|||Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination.|||Cytoplasm|||Nucleus|||The VWFA-like region is similar to the VWFA domain. Its presence reveals similarities between the structure of the 19S proteasome and the BRCA1-A complexes. http://togogenome.org/gene/10090:Txnrd2 ^@ http://purl.uniprot.org/uniprot/Q9JLT4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.|||Expressed in liver, heart, testis and kidney.|||Homodimer.|||Involved in the control of reactive oxygen species levels and the regulation of mitochondrial redox homeostasis (By similarity). Maintains thioredoxin in a reduced state. May play a role in redox-regulated cell signaling (By similarity).|||Mitochondrion|||The active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity (By similarity). http://togogenome.org/gene/10090:Tpgs2 ^@ http://purl.uniprot.org/uniprot/Q66JT5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1 (PubMed:15890843). Interacts with CSTPP1 and LRRC49 (By similarity).|||Subunit of the tubulin polyglutamylase complex (TPGC). The complex mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility.|||centriolar satellite|||cytoskeleton http://togogenome.org/gene/10090:Ndufa4l2 ^@ http://purl.uniprot.org/uniprot/Q4FZG9 ^@ Similarity ^@ Belongs to the complex I NDUFA4 subunit family. http://togogenome.org/gene/10090:Krt34 ^@ http://purl.uniprot.org/uniprot/Q9D646 ^@ Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in the hair root in the hair shaft cuticle and cortex.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Pdk2 ^@ http://purl.uniprot.org/uniprot/Q9JK42 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDK/BCKDK protein kinase family.|||Detected in heart (at protein level).|||Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3).|||Kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2 (PubMed:22360721). This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.|||Mitochondrion matrix|||No visible phenotype, due to the fact that PDK2-deficient mice have increased PDK1 levels (PubMed:21411764). Mice have lower blood glucose levels in the fed state, but not after fasting. Likewise, they display increased pyruvate dehydrogenase activity in liver and skeletal muscle in the fed state, but not after fasting. Fasting mice lacking both PDK2 and PDK4 show strongly decreased blood glucose levels, increased circulating ketone body levels leading to ketoacidosis with dangerously low blood pH levels, hypothermia, and ultimately death (PubMed:22360721).|||Up-regulated by glucose and palmitic acid. Up-regulated by PPARD. http://togogenome.org/gene/10090:Tchp ^@ http://purl.uniprot.org/uniprot/Q3TVW5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCHP family.|||Cell membrane|||Cytoplasm|||Expressed in all tissues examined, including brain, liver, small intestine, large intestine, lung and heart. Found concentrated in tubular structures within hepatocytes, and in the apical cortical region and desmosomes of the apical junctional domain in enterocytes of the small intestine. In the hair follicle, localized at the outer root sheath. Also expressed in blood vessels (at protein level).|||Interacts specifically with keratin proteins including, KRT5, KRT6A, KRT8, KRT14, KRT16 and KRT18. Interacts with KCTD17 (By similarity).|||Mitochondrion|||Tumor suppressor which has the ability to inhibit cell growth and be pro-apoptotic during cell stress. May act as a 'capping' or 'branching' protein for keratin filaments in the cell periphery. May regulate K8/K18 filament and desmosome organization mainly at the apical or peripheral regions of simple epithelial cells (By similarity). Is a negative regulator of ciliogenesis (By similarity).|||Ubiquitinated. Ubiquitination by the BCR(KCTD17) E3 ubiquitin ligase complex results in proteasomal degradation, and induces ciliogenesis.|||cytoskeleton http://togogenome.org/gene/10090:P3h1 ^@ http://purl.uniprot.org/uniprot/A2A7Q5|||http://purl.uniprot.org/uniprot/A6PW84|||http://purl.uniprot.org/uniprot/Q3V1T4 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts (By similarity).|||Belongs to the leprecan family.|||Endoplasmic reticulum|||Intron retention.|||O-glycosylated; chondroitin sulfate.|||extracellular matrix http://togogenome.org/gene/10090:Retreg3 ^@ http://purl.uniprot.org/uniprot/Q9CQV4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RETREG family.|||Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (By similarity). Required for collagen quality control in a LIR motif-dependent manner (PubMed:34338405). Mediates NRF1-enhanced neurite outgrowth (By similarity).|||Endoplasmic reticulum membrane|||Interacts with ATG8 family modifier proteins MAP1LC3A, MAP1LC3B, GABARAPL1 and GABARAPL2 (PubMed:34338405). Also interacts with ATG8 family modifier protein GABARAP (By similarity). Interacts with CANX (By similarity). Interacts with RTN4 isoform B (By similarity).|||The LIR motif interacts with ATG8 family proteins.|||Widely expressed with highest levels in brain, lung, liver, muscle and spleen (protein level) (PubMed:34338405). Mainly expressed in the central nervous system and in parenchymatous organs including liver, lung and kidney. http://togogenome.org/gene/10090:Vwc2l ^@ http://purl.uniprot.org/uniprot/Q505H4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ From 12.5 dpc to 18.5 dpc, expressed in the developing neural tissues, including several discrete regions in the forebrain, midbrain and hindbrain, as well as in the spinal cord. May be up-regulated in the course of preosteblast differentiation and matrix mineralization.|||May play a role in neurogenesis. May promote matrix mineralization (PubMed:22209847), but has been shown to weakly, but significantly inhibit BMP2 and BMP6 activity in a preosteoblastic cell line (PubMed:19852960).|||Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including VWC2L. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.|||Predominantly expressed in the brain (at protein level). Also detected in bones, including femur and calvaria, heart, lung and kidney. Isoform 5 is predominant in lung and heart, compared to isoforms 1 and 3. Isoform 4 is expressed in femur and calvaria at higher levels than isoforms 1 and 5. Isoforms 1 and 4 are expressed at higher levels than isoform 5 in kidney and brain.|||Secreted|||Synapse http://togogenome.org/gene/10090:Slc30a5 ^@ http://purl.uniprot.org/uniprot/Q8R4H9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||COPII-coated vesicle membrane|||Could homodimerize through the formation of dityrosine bonds upon oxidative stress.|||Golgi stack membrane|||Heterodimer with SLC30A6/ZNT6; form a functional zinc ion transmembrane transporter.|||Homozygous knockout mice are viable and fertile (PubMed:12095919). However, they grow poorly and display lean phenotype, muscle weakness, osteopenia due to impairment of osteoblast maturation to osteocyte and male-specific sudden cardiac death associated with bradyarrhythmia (PubMed:12095919).|||Together with SLC30A6 forms a functional proton-coupled zinc ion antiporter mediating zinc entry into the lumen of organelles along the secretory pathway. By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis. Through the transport of zinc into secretory granules of pancreatic beta-cells, plays an important role in the storage and secretion of insulin.|||Ubiquitously expressed.|||secretory vesicle membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:Krt32 ^@ http://purl.uniprot.org/uniprot/B1ATJ5|||http://purl.uniprot.org/uniprot/Q62168 ^@ Miscellaneous|||Similarity|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cuticle of the hair shaft.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Spata7 ^@ http://purl.uniprot.org/uniprot/Q80VP2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the retina (at protein level) (PubMed:19268277, PubMed:29100828, PubMed:29899041). Expressed in the choroid region and retinal pigment endothelium, within the photoreceptor layer (at protein level) (PubMed:25398945, PubMed:29100828, PubMed:29899041).|||Found in a complex with CFAP410, NEK1 and SPATA7 (By similarity). Interacts with NEK1 (By similarity). Interacts with RPGRIP1 (PubMed:25398945, PubMed:29899041). Interacts with RPGR (PubMed:29899041). Interacts with NPHP4 (PubMed:29899041). Interacts with NPHP1 (PubMed:29899041). Interacts with AHI1 (PubMed:29899041).|||Involved in the maintenance of both rod and cone photoreceptor cells (PubMed:25398945, PubMed:29100828, PubMed:29899041). Required for photoreceptor-specific localization of proximal connecting cilium (CC) proteins RPGR, AHI1, NPHP1, NPHP4, and RPGRIP1 at the distal CC, a photoreceptor-specific extension of the primary cilium transition zone (PubMed:25398945, PubMed:29100828, PubMed:29899041). Maintenance of protein localization at the photoreceptor-specific distal CC is essential for normal microtubule stability and to prevent photoreceptor degeneration (PubMed:25398945, PubMed:29899041).|||Viable and fertile with no gross morphological abnormalities (PubMed:25398945). Knockout mice show severe early-onset retinal defects and progressive photoreceptor cell degeneration (PubMed:25398945). Significant and progressive reduction in response to light, accompanied by progressive thinning of the outer nuclear layer from P15 to 7 months, loss of Spata7-interacting proteins at the distal CC, and destabilization of the photoreceptor distal connecting cilium (CC) microtubule core (PubMed:25398945, PubMed:29899041). Impaired trafficking of photoreceptor proteins between the inner and outer nuclear segments resulting in loss of photoreceptor-specific protein localization at the distal CC (PubMed:25398945). Conditional knockdown of Spata7 in the retina shows an indistinguishable phenotype from knockout mice (PubMed:29100828). Electroretinogram (ERG) recordings show a significant and progressive reduction in response to light under scotopic (dark-adapted) and photopic (light-adapted) conditions (PubMed:29100828). Amplitude of both a-wave and b-wave responses is reduced indicating defects in both rod and cone type photoreceptors (PubMed:29100828).|||cilium axoneme|||cilium basal body|||cytoskeleton|||photoreceptor outer segment http://togogenome.org/gene/10090:Galntl5 ^@ http://purl.uniprot.org/uniprot/Q9D4M9 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Contaminating sequence. Potential poly-A sequence.|||Expressed in testis. Mainly expressed in the round and elongated spermatids during spermiogenesis, not in the outermost cells of the seminiferous tubules, which contain spermatogonia and somatic Sertoli cells. Present in the juxtanuclear space in the round spermatids, not in the acrosomal vesicles. In the elongating spermatids, localizes strongly in the acroplaxome, the region between the developing acrosome and nucleus. During differentiation, also weakly detected in the transient manchette containing microtubules. In epididymal spermatozoa, weakly detected in the midpiece, but concentrates mainly in the neck region around the head-tail coupling apparatus (at protein level).|||Heterozygous mice show male infertility because of immotile sperm: glycolytic enzymes required for sperm motility are decreased, their protein loading into acrosomes disrupted, and aberrant localization of the ubiquitin-proteasome system is observed. Females show normal fertility.|||In contrast to other members of the family, lacks the C-terminal ricin B-type lectin domain that contributes to the glycopeptide specificity, and lacks the conserved His residue in position 341. No glycosyltransferase activity has been detected in an in vitro assay (PubMed:24398516).|||Late endosome membrane|||Probable inactive glycosyltransferase required during spermatid development. May participate in protein loading into the acrosomes and accumulation of ubiquitin-proteasome systems around the head-tail coupling apparatus region.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Prex1 ^@ http://purl.uniprot.org/uniprot/Q69ZK0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Functions as a RAC guanine nucleotide exchange factor (GEF), which activates the Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. May function downstream of heterotrimeric G proteins in neutrophils (By similarity).|||Interacts preferentially with RAC2 (PubMed:16243036). Interacts with RAC1 (PubMed:16243036). Interacts with AUTS2 (PubMed:25533347).|||cytosol http://togogenome.org/gene/10090:Plppr4 ^@ http://purl.uniprot.org/uniprot/Q7TME0 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PA-phosphatase related phosphoesterase family.|||Brain-specific, it is exclusively expressed in neurons (at protein level).|||Knockout mice lacking Plppr4 are viable but show a severe alteration of synaptic transmission leading to juvenile epileptic seizures (PubMed:19766573). Excitatory transmission in CA1 pyramidal neurons is significantly increased (PubMed:19766573). It is associated with transiently reduced weight during development, a reduction in brain size and higher mortality 3 to 4 weeks after birth (PubMed:19766573). Heterozygous knockout mice, show loss of somatosensory filter function and altered resilience during stress-related behaviors (PubMed:26671989).|||O-glycosylated. Probably at Ser-347.|||Originally described as a 2-lysophosphatidate/LPA phosphatase (PubMed:12730698). However, following studies suggested it does not have such activity or only a residual one (PubMed:19766573). This is further supported by the fact that the phosphatase sequence motifs as well as the His residue acting as a nucleophile in active phosphatases of the PA-phosphatase related phosphoesterase family are not conserved (PubMed:19766573).|||Postsynaptic density membrane|||Postsynaptic density membrane protein that indirectly regulates glutamatergic synaptic transmission through lysophosphatidic acid (LPA)-mediated signaling pathways (PubMed:19766573). Binds lysophosphatidic acid (LPA) and mediates its internalization into cells (PubMed:26671989). Could act as receptor or a transporter of this lipid at the post-synaptic membrane (PubMed:19766573, PubMed:26671989). Modulates lysophosphatidic acid (LPA) activity in neuron axonal outgrowth during development by attenuating phospholipid-induced axon collapse (By similarity). http://togogenome.org/gene/10090:Fam53c ^@ http://purl.uniprot.org/uniprot/Q8BXQ8 ^@ Similarity ^@ Belongs to the FAM53 family. http://togogenome.org/gene/10090:Itm2b ^@ http://purl.uniprot.org/uniprot/O89051 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ITM2 family.|||Bri23 peptide prevents aggregation of APP amyloid-beta protein 42 into toxic oligomers.|||Cell membrane|||Endosome membrane|||Expressed in the brain, testis, testicular sperm, epididymis and mature epididymal sperm (at protein level).|||Glycosylation at Asn-170 is important for cell surface localization, but doesn't affect furin- and ADAM10-induced proteolytic processing.|||Golgi apparatus membrane|||Homodimer; disulfide-linked. Interacts with SPPL2A and SPPL2B. Interacts with APP. Mature BRI2 (mBRI2) interacts with the APP amyloid-beta A4 protein; the interaction occurs at the cell surface and in the endocytic compartments and enable alpha- and beta-secretase-induced APP cleavage inhibition. Mature BRI2 (mBRI2) interacts with the APP C99; the interaction occurs in the endocytic compartments and enable gamma-secretase-induced C99 cleavage inhibition. May form heterodimers with Bri23 peptide and APP amyloid-beta protein 40 (By similarity). Interacts with ADAM7 in sperm; the interaction increases following capacitation (PubMed:20945367).|||Mature BRI2 (mBRI2) functions as a modulator of the amyloid-beta A4 precursor protein (APP) processing leading to a strong reduction in the secretion of secretase-processed amyloid-beta protein 40 and amyloid-beta protein 42.|||Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition. Plays a role in the induction of neurite outgrowth. Functions as a protease inhibitor by blocking access of secretases to APP cleavage sites (By similarity).|||Secreted|||The ectodomain C-terminal part of the imBRI2 is processed by furin producing a secreted Bri23 peptide and a mature BRI2, membrane form (mBRI2). The remaining part of the ectodomain of mBRI2 containing the BRICHOS domain is cleaved by ADAM10 and is secreted (BRI2C, soluble form). The membrane-bound N-terminal fragment (BRI2C, membrane form) is further proteolytically processed by SPPL2A and SPPL2B through regulated intramembrane proteolysis producing a secreted C-peptide and a BRI2 intracellular domain (BRI2 ICD) released in the cytosol. Shedding by ADAM10 facilitates intramembrane cleavage but is not absolutely required for BRI2 ICD generation (By similarity). http://togogenome.org/gene/10090:Trim6 ^@ http://purl.uniprot.org/uniprot/Q8BGE7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||E3 ubiquitin ligase that plays a crucial role in the activation of the IKBKE-dependent branch of the type I interferon signaling pathway (PubMed:24882218). In concert with the ubiquitin-conjugating E2 enzyme UBE2K, synthesizes unanchored 'Lys-48'-linked polyubiquitin chains that promote the oligomerization and autophosphorylation of IKBKE leading to stimulation of an antiviral response (PubMed:24882218). Ubiquitinates also MYC and inhibits its transcription activation activity, maintaining the pluripotency of embryonic stem cells (PubMed:22328504). Promotes the association of unanchored 'Lys-48'-polyubiquitin chains with DHX16 leading to enhancement of RIGI-mediated innate antiviral immune response (By similarity).|||Homotrimer. Forms heteromultimers (via B30.2/SPRY domain) with TRIM5 (By similarity). Interacts with MYC (PubMed:22328504). Interacts (via SPRY domain) with IKBKE (By similarity). Interacts with VAMP8; this interaction contributes to the activation of the type I interferon antiviral response (By similarity). Interacts with DHX16 (By similarity).|||The B-box zinc finger and the linker region between the coiled coil and B30.2/SPRY domains contribute to higher order self-association. http://togogenome.org/gene/10090:Irx3 ^@ http://purl.uniprot.org/uniprot/P81067 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TALE/IRO homeobox family.|||Expressed by neural progenitor cells in discrete domains of the ventral neural tube. Also expressed in specific and overlapping patterns with Irx1 and Irx2 in the developing and adult metanephric kidney. In the adult metanephros, renal expression is confined to the S3 segment of the proximal tubule, in the loop of Henle.|||Mice are viable and fertile but display a significant reduction of body weight, primarily through the loss of fat mass and increase in basal metabolic rate with browning of white adipose tissue.|||Nucleus|||The earliest expressed of the Irx family, with expression seen in trophectoderm-derived extraembryonic tissues from 6.5 dpc, including expression in the chorionic ectoderm at 8.0 dpc. Embryonic expression starts at the end of gastrulation (7.5 dpc) in the ectodermal layer which gives rise to the nervous system. At 8.0 dpc, expression is confined to the thickening neural ectoderm corresponding to the future mesencephalon (midbrain) and rhombencephalon (hindbrain) and from 8.5 dpc onwards, expression also includes the rostral part of the closing neural tube. After neural tube closure at 9.5 dpc, expression predominates in the CNS in the midbrain, hindbrain and spinal cord. Also expressed in a number of tissues outside of the CNS including ectodermal layer of the branchial arches. Expressed in the prospective limb buds of the lateral plate mesoderm, and from 10.5 dpc onwards a gradient exists along the dorsoventral and proximodistal axes of developing limbs. Expressed in the notochord at stage 9.0 dpc. At 9.5 dpc found in the cephalic mesoderm surrounding the optic vesicle. Around 10.5 dpc, expression in the head mesoderm extends into the nasal pits. By 12.5 dpc, still expressed in the mesenchyme, and expressions begins in specific subsets of post-mitotic cells in the neuroretina. As development ensues, expression increases in the neuroretina and mesenchymal expression gradually decreases. At 16.5 dpc, expressed exclusively in the inner neuroblast layers of the neuroretina. In the developing heart, first expressed in the trabecules of embryonic ventricles at 9.5 dpc, and from then onwards localizes specifically to the trabeculated myocardium of the ventricles.|||Transcription factor involved in SHH-dependent neural patterning (PubMed:10830170, PubMed:15201216). Together with NKX2-2 and NKX6-1 acts to restrict the generation of motor neurons to the appropriate region of the neural tube (PubMed:10830170, PubMed:15201216). Belongs to the class I proteins of neuronal progenitor factors, which are repressed by SHH signals (PubMed:10830170, PubMed:15201216). Involved in the transcriptional repression of MNX1 in non-motor neuron cells (PubMed:15201216). Acts as a regulator of energy metabolism (PubMed:24646999). http://togogenome.org/gene/10090:Cxcl14 ^@ http://purl.uniprot.org/uniprot/Q9WUQ5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Chemotactic for CESS B-cells and THP-1 monocytes, but not T-cells.|||Highly expressed in brain, lung, ovary, muscle and in kidney and liver parenchyma, and at lower levels in bone marrow.|||Secreted|||The destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.|||Ubiquitinated, followed by degradation by the proteasome. http://togogenome.org/gene/10090:Id2 ^@ http://purl.uniprot.org/uniprot/P41136|||http://purl.uniprot.org/uniprot/Q545T4 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Expressed in a circadian manner in the liver with peak levels seen at CT12 (at protein level). Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain and heart with peak levels seen between CT16 and CT20 in the SCN and between CT8 and CT12 in the heart.|||Interacts with NR0B2 (By similarity). Interacts with CLOCK and BMAL1 (By similarity). Interacts with GATA4 and NKX2-5 (PubMed:16556596). Interacts with IFI204 (PubMed:11940648). Interacts with NEDD9/HEF1 (By similarity).|||Mice exhibit disrupted locomotor rhythms, reduced locomotor activity, enhanced phase shifts and an increased rate of entrainment when subjected to a large delay of the photoschedule. Show a reduction in lipid storage in the liver and white adipose tissue.|||Nucleus|||Polyubiquitinated; which is favored by Ifi204 and leads to proteasomal degradation.|||The bHLH domain is essential for its repressor activity towards the CLOCK-BMAL1 heterodimer.|||Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Inhibits skeletal muscle and cardiac myocyte differentiation. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Restricts the CLOCK and BMAL1 localization to the cytoplasm. Plays a role in both the input and output pathways of the circadian clock: in the input component, is involved in modulating the magnitude of photic entrainment and in the output component, contributes to the regulation of a variety of liver clock-controlled genes involved in lipid metabolism. http://togogenome.org/gene/10090:Or5l14 ^@ http://purl.uniprot.org/uniprot/A2AVC4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rfx3 ^@ http://purl.uniprot.org/uniprot/G5E890|||http://purl.uniprot.org/uniprot/P48381 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RFX family.|||Expressed in ciliated cells of the node and in the ciliated ependymal cells of the subcommissural organ (SCO), choroid plexuses (CP) and ventricular walls during embryonic and postnatal development. Expressed in developing and mature pancreatic endocrine cells during embryogenesis and in adults (at protein level).|||Heterodimer; heterodimerizes with RFX1 and RFX2, and RFX6.|||High rate of embryonic lethality. 2 peaks of death are observed: approximately half of the embryos die around days 11 or 12 of embryonic development. Of the embryos that survive past this stage, approximately two-thirds die at birth. Surviving mice are systematically smaller. Their body weights at birth are approximately one-third lower. This growth retardation increases with age, and the body weights that adult male or female mice attain are less than half those of wild-type mice. Mice exhibit a pronounced defect in nodal cilia: cilia are present but remain markedly stunted. Mice also suffer from hydrocephalus without stenosis of the aqueduct of Sylvius. In pancreatic endocrine cells, primary cilia are reduced in number and severely stunted: this ciliary abnormality is associated with a developmental defect leading to an altered cellular composition of the islets of Langerhans. Just before birth, islets contain considerably less insulin-, glucagon-, and ghrelin-producing cells, whereas pancreatic PP (polypeptide-producing) cells are markedly increased in number. In adult mice, the defect leads to small and disorganized islets, reduced insulin production, and impaired glucose tolerance.|||Nucleus|||Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development. Essential for the differentiation of nodal monocilia and left-right asymmetry specification during embryogenesis. Required for the biogenesis of motile cilia by governing growth and beating efficiency of motile cells (PubMed:15121860, PubMed:19671664). Also required for ciliated ependymal cell differentiation (PubMed:16930429). Together with RFX6, participates in the differentiation of 4 of the 5 islet cell types during endocrine pancreas development, with the exception of pancreatic PP (polypeptide-producing) cells (PubMed:17229940). Regulates transcription by forming a heterodimer with another RFX protein and binding to the X-box in the promoter of target genes (By similarity). Regulates the expression of genes involved in ciliary assembly (DYNC2LI1, FOXJ1 and BBS4) and genes involved in ciliary motility (DNAH11, DNAH9 and DNAH5). Represses transcription of MAP1A in non-neuronal cells but not in neuronal cells. http://togogenome.org/gene/10090:Prdm9 ^@ http://purl.uniprot.org/uniprot/E9Q4V2 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rhox3g ^@ http://purl.uniprot.org/uniprot/B9EJQ9 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rpsa ^@ http://purl.uniprot.org/uniprot/P14206 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acylated. Acylation may be a prerequisite for conversion of the monomeric 37 kDa laminin receptor precursor (37LRP) to the mature dimeric 67 kDa laminin receptor (67LR), and may provide a mechanism for membrane association.|||Belongs to the universal ribosomal protein uS2 family.|||Cell membrane|||Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage by stromelysin-3 may be a mechanism to alter cell-extracellular matrix interactions.|||Cytoplasm|||It is thought that in vertebrates 37/67 kDa laminin receptor acquired a dual function during evolution. It developed from the ribosomal protein SA, playing an essential role in the protein biosynthesis lacking any laminin binding activity, to a cell surface receptor with laminin binding activity.|||Monomer (37LRP) and homodimer (67LR) (By similarity). Component of the small ribosomal subunit (PubMed:36517592). Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S) (PubMed:36517592). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S) (PubMed:36517592). Interacts with RPS21 (By similarity). Interacts with several laminins including at least LAMB1. Interacts with MDK. Interacts with PRNP. The mature dimeric form interacts with PPP1R16B (via its fourth ankyrin repeat). Interacts with PPP1CA only in the presence of PPP1R16B (By similarity).|||Nucleus|||Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis. Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria. Acts as a PPP1R16B-dependent substrate of PPP1CA (By similarity). Enables malignant tumor cells to penetrate laminin tissue and vessel barriers. Activates precursor thymic anti-OFA/iLRP specific cytotoxic T-cell. May induce CD8 T-suppressor cells secreting IL-10.|||This protein appears to have acquired a second function as a laminin receptor specifically in the vertebrate lineage. http://togogenome.org/gene/10090:Zfp444 ^@ http://purl.uniprot.org/uniprot/Q3TDV8 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Dld ^@ http://purl.uniprot.org/uniprot/O08749 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.|||Binds 1 FAD per subunit.|||Expressed in liver (at protein level).|||Homodimer. Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDHA (PDHA1 or PDHA2) and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (by non covalent bonds). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A. Interacts with PDHX.|||Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (By similarity). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (By similarity). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (By similarity). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity).|||Mitochondrion matrix|||Nucleus|||The active site is a redox-active disulfide bond.|||Tyrosine phosphorylated.|||acrosome|||flagellum http://togogenome.org/gene/10090:Ndufb3 ^@ http://purl.uniprot.org/uniprot/Q9CQZ6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFB3 subunit family.|||Complex I is composed of 45 different subunits.|||Methylation at His residues by METTL9 enhances complex I-mediated mitochondrial respiration.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Arid2 ^@ http://purl.uniprot.org/uniprot/E9Q7E2|||http://purl.uniprot.org/uniprot/Q9D982 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RFX family.|||Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin. Interacts with SRF. Forms complexes with SRF and SRF cofactors MYOCD, NKX2-5 and SRFBP1.|||Highly expressed in testis, expressed in heart, liver and kidney.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Required for the stability of the SWI/SNF chromatin remodeling complex SWI/SNF-B (PBAF). May be involved in targeting the complex to different genes. May be involved in regulating transcriptional activation of cardiac genes.|||Nucleus http://togogenome.org/gene/10090:Gimap8 ^@ http://purl.uniprot.org/uniprot/A0A0R3P9C7|||http://purl.uniprot.org/uniprot/Q75N62 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in the thymus (in thymocytes), spleen (in splenocytes), lymph node, followed by bone marrow and lung.|||Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.|||Endoplasmic reticulum|||Exerts an anti-apoptotic effect in the immune system and is involved in responses to infections.|||Golgi apparatus|||Mitochondrion|||cytosol http://togogenome.org/gene/10090:Cartpt ^@ http://purl.uniprot.org/uniprot/P56388|||http://purl.uniprot.org/uniprot/Q3UYI4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CART family.|||Satiety factor closely associated with the actions of leptin and neuropeptide y; this anorectic peptide inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus.|||Secreted http://togogenome.org/gene/10090:9930111J21Rik2 ^@ http://purl.uniprot.org/uniprot/Q8CB10 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Lamtor5 ^@ http://purl.uniprot.org/uniprot/G3UW70|||http://purl.uniprot.org/uniprot/Q9D1L9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. When complexed to BIRC5, interferes with apoptosome assembly, preventing recruitment of pro-caspase-9 to oligomerized APAF1, thereby selectively suppressing apoptosis initiated via the mitochondrial/cytochrome c pathway.|||Belongs to the LAMTOR5 family.|||Homodimer. Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer. The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability. The Ragulator complex interacts with SLC38A9; the probable amino acid sensor. Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interacts with phosphorylated BIRC5; the resulting complex binds pro-caspase-9, as well as active caspase-9, but much less efficiently. Interacts with SUPV3L1.|||Lysosome|||cytosol http://togogenome.org/gene/10090:Xcl1 ^@ http://purl.uniprot.org/uniprot/P47993|||http://purl.uniprot.org/uniprot/Q542T1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the intercrine gamma family.|||Chemotactic activity for lymphocytes but not for monocytes or neutrophils. In thymus, mediates medullary accumulation of thymic dendritic cells and contributes to regulatoy T cell development, playing a role in self-tolerance establishment.|||Expressed in activated CD8(+) T cells. In the thymus, expressed by medullary thymic epithelial cells.|||Secreted|||The thymus of knockout mice shows a lower medullary accumulation of dendritic cells. Animals have a defective generation of naturally ocurring regulatory T cells. http://togogenome.org/gene/10090:Sdhaf2 ^@ http://purl.uniprot.org/uniprot/Q8C6I2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SDHAF2 family.|||Interacts with SDHA within the SDH catalytic dimer.|||Mitochondrion matrix|||Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Required for flavinylation (covalent attachment of FAD) of the flavoprotein subunit SDHA of the SDH catalytic dimer. http://togogenome.org/gene/10090:Rbfa ^@ http://purl.uniprot.org/uniprot/Q6P3B9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the RbfA family.|||Mitochondrion http://togogenome.org/gene/10090:Akr1c19 ^@ http://purl.uniprot.org/uniprot/G3X9Y6 ^@ Similarity ^@ Belongs to the aldo/keto reductase family. http://togogenome.org/gene/10090:Ppfia3 ^@ http://purl.uniprot.org/uniprot/P60469 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the liprin family. Liprin-alpha subfamily.|||Cytoplasm|||Detected in sperm (at protein level).|||Forms homodimers and heterodimers with liprins-alpha and liprins-beta. Interacts with the second PTPase domain of PTPRD, PTPRF and PTPRS. Binds RIMS1, RIMS2, RIMS3 and RIMS4.|||May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates.|||The N-terminal coiled coil regions mediate homodimerization preferentially and heterodimerization type alpha/alpha. The C-terminal, non-coiled coil regions mediate heterodimerization type alpha/beta and interaction with PTPRD, PTPRF and PTPRS.|||acrosome http://togogenome.org/gene/10090:Or10g9 ^@ http://purl.uniprot.org/uniprot/Q8VH10 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Sftpd ^@ http://purl.uniprot.org/uniprot/P50404 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SFTPD family.|||Contributes to the lung's defense against inhaled microorganisms, organic antigens and toxins. Interacts with compounds such as bacterial lipopolysaccharides, oligosaccharides and fatty acids and modulates leukocyte action in immune response. May participate in the extracellular reorganization or turnover of pulmonary surfactant. Binds strongly maltose residues and to a lesser extent other alpha-glucosyl moieties.|||Oligomeric complex of 4 set of homotrimers.|||Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).|||S-nitrosylation at Cys-34 and Cys-39 alters the quaternary structure which results in a pro-inflammatory chemoattractive signaling activity with macrophages.|||extracellular matrix|||surface film http://togogenome.org/gene/10090:Defb9 ^@ http://purl.uniprot.org/uniprot/Q8R2I6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted|||Weakly expressed in adult and neonatal brain. http://togogenome.org/gene/10090:Try5 ^@ http://purl.uniprot.org/uniprot/Q9QUK9 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by autocatalytic cleavage (PubMed:23814066). Cleavage by CTRC inhibits autoactivation (PubMed:23814066).|||Belongs to the peptidase S1 family.|||Expressed in the heart, lung, brain, kidney, liver, epididymis, ovary and uterus. Expression in the testis is limited to round and elongating spermatids.|||Expressed in the testis from 20 days of age onwards.|||Proteolytically cleaved and activated by an autocatalytic mechanism (PubMed:23814066). Cleavage by CTRC inhibits autoactivation (PubMed:23814066).|||Serine protease capable of autoactivation.|||acrosome http://togogenome.org/gene/10090:Lmf1 ^@ http://purl.uniprot.org/uniprot/Q3U3R4 ^@ Caution|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Additional evidence for its localization to the endoplasmic reticulum membrane was found. However this paper was retracted due to manipulation of data.|||Belongs to the lipase maturation factor family.|||Defects in Lmf1 are the cause of combined lipase deficiency (cld). Cld is characterized by severe hypertriglyceridemia with accumulation of chylomicrons that gradually pack the lumina of capillaries and sinusoids. Severe hypertriglyceridemia causes an increase in blood viscosity, ischemia, and cyanosis, and the inability of tissues to access circulating triglycerides results in starvation, poor thermoregulation, and death 2 to 3 days after birth. The disorder is caused by a decrease in the activity of lipoprotein lipase (Lpl) and the related hepatic lipase (Lipc), caused by impaired maturation of nascent Lpl and hepatic lipase polypeptides in the endoplasmic reticulum.|||Endoplasmic reticulum membrane|||Expressed in all tissues synthesizing lipoprotein lipase (Lpl) and hepatic lipase (Lipc), including adipose tissue, skeletal muscle, heart, and liver. Expressed at higher levels in tissues that express little or no lipase activity such as testis and pancreas suggesting additional functions in these tissues.|||Interacts with LPL and SEL1L.|||Involved in the maturation of specific proteins in the endoplasmic reticulum. Required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway. Each LMF1 molecule chaperones 50 or more molecules of LPL. http://togogenome.org/gene/10090:Or8g50 ^@ http://purl.uniprot.org/uniprot/Q60895 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. http://togogenome.org/gene/10090:Xlr4c ^@ http://purl.uniprot.org/uniprot/Q3TKR2 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Hlf ^@ http://purl.uniprot.org/uniprot/Q8BW74 ^@ Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accumulates according to a robust circadian rhythm. Displays only a moderate amplitude in the liver (1.6-fold) and none in the brain.|||Belongs to the bZIP family. PAR subfamily.|||Binds DNA specifically as homodimer or heterodimer with other PAR factors.|||Mice deficient for all three PAR bZIP proteins (DBP, HLF and TEF) display a dramatically shortened life span and are highly susceptible to generalized spontaneous and audiogenic epilepsies (due for example to the noise of a vacuum cleaner) that are frequently lethal. The down-regulation of pyridoxal kinase (Pdxk) expression in these mice may participate in this seizure phenotype.|||Nucleus http://togogenome.org/gene/10090:Nemp2 ^@ http://purl.uniprot.org/uniprot/Q8CB65 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NEMP family.|||In the ovary, highly expressed in somatic cells.|||Nucleus inner membrane http://togogenome.org/gene/10090:Gp2 ^@ http://purl.uniprot.org/uniprot/Q9D733 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Cell membrane|||Each ZP domain consists of an N-terminal (ZP-N) and C-terminal (ZP-C) region connected by a flexible linker; the linker allows the ZP domain to wrap around the ZP-C subdomain of the preceding subunit.|||Endosome|||Functions as an intestinal M-cell transcytotic receptor specific of type-I-piliated bacteria that participates in the mucosal immune response toward these bacteria. At the apical membrane of M-cells it binds fimH, a protein of the bacteria type I pilus tip. Internalizes bound bacteria, like E.coli and S.typhimurium, from the lumen of the intestine and delivers them, through M-cells, to the underlying organized lymphoid follicles where they are captured by antigen-presenting dendritic cells to elicit a mucosal immune response.|||Interacts with SYCN. Interacts with bacterial adhesin fimH.|||Knockout mice lacking Gp2 fail to induce antigen-specific helper-T-cells and antibody immune responses after oral immunization with FimH positive bacteria (PubMed:19907495). This is not due to a general defect in the immunological functions, since a normal response is induced by other systemic immunizations (PubMed:19907495).|||Membrane raft|||N-glycosylated.|||Secreted|||Specifically expressed by M (microfold) cells which are atypical epithelial cells of the intestine.|||Zymogen granule membrane http://togogenome.org/gene/10090:Apbb1 ^@ http://purl.uniprot.org/uniprot/Q9QXJ1 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation at Lys-204 and Lys-701 by KAT5 promotes its transcription activator activity.|||Cell membrane|||Component of a complex, at least composed of APBB1, RASD1/DEXRAS1 and APP (By similarity). Interacts (via PID domain 2) with APP (with the intracellular domain of the amyloid-beta precursor protein) (By similarity). Interacts (via PID domain 2) with RASD1/DEXRAS1; impairs the transcription activation activity (By similarity). Interacts (via PID domain 1) with KAT5/TIP60 (By similarity). Interacts (via the WW domain) with the proline-rich region of APBB1IP (PubMed:9407065). Interacts with TSHZ1 and TSHZ2 (PubMed:19343227). Interacts (via the WW domain) with histone H2AX (when phosphorylated on 'Tyr-142') and the proline-rich region of ENAH (PubMed:9407065). Interacts with MAPK8 (By similarity). Interacts (via PID domain 1) with TSHZ3 (via homeobox domain) (By similarity). Interacts with SET (By similarity). Found in a trimeric complex with HDAC1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (By similarity). Interacts (via WWW domain) with NEK6. Interacts (via WWW domain) with ABL1. Interacts with RNF157 (By similarity).|||Cytoplasm|||Expressed in the brain, retinal lens and muscle cells (at protein level).|||No phenotype in normal conditions (PubMed:17121854). Displays an increased sensitivity to genotoxic stress and exposure to DNA damaging agents (PubMed:17121854). Knockout mice have decreased muscle strength, however clasping ability is unaffected (PubMed:25757569). Impaired spatial memory retrieval and learning (PubMed:27734846). Reduced branching of hippocampal neurites and increased fragmentation of neuromuscular junctions (PubMed:27734846). APBB1 and APBB2 double knockout mice show progressive retinal lens disruption from 1 month of age, morphologically lenses show massive vacuolization, lens capsule rupture and disruption of the lens fiber cells organization (PubMed:25757569). Decreased muscle strength, however clasping ability is unaffected (PubMed:25757569, PubMed:27734846). Defects in peripheral motor function including balance and coordination, reduced environmental anxiety, reduced hippocampal basal synaptic transmission and synaptic plasticity (PubMed:27734846).|||Nucleus|||Nucleus speckle|||Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity). Phosphorylated following nuclear translocation. Phosphorylation at Tyr-546 by ABL1 enhances transcriptional activation activity and reduces the affinity for RASD1/DEXRAS1 (By similarity).|||Polyubiquitination by RNF157 leads to degradation by the proteasome (PubMed:25342469).|||Transcription coregulator that can have both coactivator and corepressor functions (PubMed:17121854, PubMed:25342469). Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain (PubMed:17121854, PubMed:25342469). Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs) (By similarity). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its transcription activation activity (By similarity). Functions in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s) (By similarity). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (PubMed:27734846). Plays a role in the maintenance of lens transparency (PubMed:25757569). May play a role in muscle cell strength (PubMed:25757569, PubMed:27734846).|||growth cone http://togogenome.org/gene/10090:Cyp2d34 ^@ http://purl.uniprot.org/uniprot/L7N463 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Mrgprx1 ^@ http://purl.uniprot.org/uniprot/Q8CIP3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed in a subset of IB4-positive small diameter nociceptive dorsal root neurons.|||Orphan receptor activated by neuropeptides terminating in Arg-Phe or Arg-Phe-amide. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. May regulate the function of nociceptive neurons by modulation of pain perception. http://togogenome.org/gene/10090:Cd48 ^@ http://purl.uniprot.org/uniprot/P18181 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Deletion mice do not develop signs of autoimmunity, but exhibit defects in induction of tolerance.|||Glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that interacts via its N-terminal immunoglobulin domain with cell surface receptors including 2B4/CD244 or CD2 to regulate immune cell function and activation (PubMed:9881969, PubMed:21278219). Participates in T-cell signaling transduction by associating with CD2 and efficiently bringing the Src family protein kinase LCK and LAT to the TCR/CD3 complex. In turn, promotes LCK phosphorylation and subsequent activation (PubMed:9881969). Induces the phosphorylation of the cytoplasmic immunoreceptortyrosine switch motifs (ITSMs) of CD244 initiating a series of signaling events that leads to the generation of the immunological synapse and the directed release of cytolytic granules containing perforin and granzymes by T-lymphocytes and NK-cells (By similarity) (PubMed:9881969, PubMed:21278219).|||Interacts with CD2 (PubMed:1383383). Interacts with CD244 (PubMed:17950006). Interacts with LCK (By similarity).|||Secreted http://togogenome.org/gene/10090:Or4k41 ^@ http://purl.uniprot.org/uniprot/Q7TQY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fli1 ^@ http://purl.uniprot.org/uniprot/P26323|||http://purl.uniprot.org/uniprot/Q544B3|||http://purl.uniprot.org/uniprot/Q8BZ56 ^@ Disease Annotation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Can form homodimers or heterodimers with ETV6/TEL1.|||Expressed in both hematopoietic and nonhematopoietic tissues.|||Involved in erythroleukemia induction by Friend murine leukemia virus (F-MULV).|||Nucleus|||Sequence-specific transcriptional activator. Recognizes the DNA sequence 5'-C[CA]GGAAGT-3'.|||Specifically up-regulated in leukemic clones with F-MuLV insertions up-stream of the FLI-1 locus. http://togogenome.org/gene/10090:Klra6 ^@ http://purl.uniprot.org/uniprot/Q60653 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked.|||Membrane|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Gm21466 ^@ http://purl.uniprot.org/uniprot/A0A571BDE3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Gpihbp1 ^@ http://purl.uniprot.org/uniprot/Q9D1N2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adult mice display chylomicronemia when kept on a normal chow diet, with milky-looking blood plasma due to marked accumulation of chylomicrons in the plasma. Their plasma triglyceride levels are generally above 1000 mg/dl and can be as high as 5000 mg/dl. Mice display decreased plasma levels of lipoprotein lipase LPL (PubMed:17403372). Contrary to wild-type, LPL is not recruited to the apical surface of endothelial cell that faces the lumen of capillaries, but is mislocalized to the interstitial spaces surrounding myocytes and adipocytes (PubMed:20620994, PubMed:24726386, PubMed:27811232).|||Apical cell membrane|||Basolateral cell membrane|||Cell membrane|||Detected in fat tissue (PubMed:18340083, PubMed:17403372). Detected on the luminal surface of capillary endothelial cells in heart, skeletal muscle and brown adipose tissue (at protein level) (PubMed:17403372, PubMed:20620994). Detected in heart and brown adipose tissue (PubMed:12496272, PubMed:17403372). Expressed at lower levels in lung and liver (PubMed:12496272).|||Glycosylation of Asn-76 is critical for cell surface localization.|||Induced by fasting.|||Mediates the transport of lipoprotein lipase LPL from the basolateral to the apical surface of endothelial cells in capillaries (PubMed:20620994). Anchors LPL on the surface of endothelial cells in the lumen of blood capillaries (PubMed:20620994, PubMed:24726386, PubMed:27811232). Thereby, plays an important role in lipolytic processing of chylomicrons by LPL, triglyceride metabolism and lipid homeostasis (PubMed:17403372). Binds chylomicrons and phospholipid particles that contain APOA5 (PubMed:18340083). Binds high-density lipoprotein (HDL) and plays a role in the uptake of lipids from HDL (PubMed:12496272).|||Mostly monomer, but also homodimer and homooligomer (PubMed:25387803). Interacts with lipoprotein lipase (LPL) (PubMed:17403372, PubMed:18340083, PubMed:19304573, PubMed:20620994, PubMed:25387803, PubMed:24726386, PubMed:27811232). Interacts with high affinity with high-density lipoprotein (HDL) (PubMed:12496272). Interacts with chylomicrons (PubMed:17403372). Interacts with APOA5 (PubMed:18340083).|||Sulfation of a Tyr in the N-terminal acidic region increases the affinity for LPL.|||The N-terminal acidic region is intrinsically disordered (By similarity). This region contributes to LPL binding (PubMed:20620994). It stabilizes LPL and protects LPL against loss of activity (By similarity). http://togogenome.org/gene/10090:Tbc1d10a ^@ http://purl.uniprot.org/uniprot/P58802 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as GTPase-activating protein for RAB27A.|||Binds to the first PDZ domain of NHERF1 and NHERF2.|||Expressed in most tissues, except for skeletal muscle.|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.|||microvillus http://togogenome.org/gene/10090:Cpsf1 ^@ http://purl.uniprot.org/uniprot/Q9EPU4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CPSF1 family.|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. This subunit is involved in the RNA recognition step of the polyadenylation reaction (By similarity). May play a role in eye morphogenesis and the development of retinal ganglion cell projections to the midbrain (By similarity).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with FIP1L1 and SRRM1. Interacts with TUT1; the interaction is direct and mediates the recruitment of the CPSF complex on the 3'UTR of selected pre-mRNAs (By similarity). Interacts with TENT2/GLD2.|||nucleoplasm http://togogenome.org/gene/10090:Gde1 ^@ http://purl.uniprot.org/uniprot/Q9JL56 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Cell membrane|||Cytoplasmic vesicle membrane|||Hydrolyzes the phosphodiester bond of glycerophosphodiesters such as glycerophosphoinositol (GroPIns) and glycerophosphoethanolamine (GroPEth), to yield a glycerol phosphate and an alcohol (PubMed:18227059, PubMed:21801852, PubMed:25596343). Hydrolyzes glycerophospho-N-acylethanolamines to N-acylethanolamines in the brain and participates in bioactive N-acylethanolamine biosynthesis such as anandamide (an endocannabinoid), N-palmitoylethanolamine (an anti-inflammatory), and N-oleoylethanolamine (an anorexic) (PubMed:18227059). In addition, has a lysophospholipase D activity by hydrolyzing N-acyl-lysoplasmenylethanolamine (N-acyl-lysoPlsEt) to N-acylethanolamine (PubMed:21801852, PubMed:25596343). However lysophospholipase D activity is lower than glycerophosphodiester phosphodiesterase activity (PubMed:21801852, PubMed:25596343). Has little or no activity towards glycerophosphocholine (By similarity).|||Inhibited by EDTA, calcium chloride, and zinc chloride (PubMed:18227059, PubMed:25596343). Enhanced by magnesium chloride (PubMed:18227059, PubMed:25596343). Glycerophosphodiester phosphodiesterase activity can be modulated by G-protein signaling pathways (By similarity).|||Interacts with PRAF2 (By similarity). Interacts with RGS16 (By similarity).|||N-glycosylated.|||Widely expressed (PubMed:10760272). Highly expressed in the brain and spinal cord, followed by kidney, liver, and testis. In contrast, little or no expression is detected in the heart or spleen (PubMed:18227059). http://togogenome.org/gene/10090:Actl6b ^@ http://purl.uniprot.org/uniprot/Q99MR0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the actin family.|||By retinoic acid of P19 embryonic carcinoma stem cells induced by this treatment to differentiate into neuronal cells.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (PubMed:22952240, PubMed:26601204).Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (By similarity). Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A or SMARCD2/BAF60B or SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (ACTB)(PubMed:12368262, PubMed:17640523, PubMed:17920018). Note that the nBAF complex is polymorphic in regard to the ATPase, SMARCA2 and SMARCA4 occupying mutually exclusive positions (PubMed:12368262). May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (By similarity).|||Expression begins near the time of neuronal cell type specification. First apparent at 10.5 dpc in the nervous system, with high levels in the telencephalon and less in the diencephalon, mesencephalon and spinal cord. This pattern of expression persists and becomes more defined at 12.5 dpc and later stages. Detected in dorsal root ganglia, but not in neural crest derivatives that give rise to non-neuronal tissues, including great vessels. Expressed in postmitotic cells in the CNS, but not in actively proliferating precursor cells. At protein level, first detected at 12.5 dpc in nervous tissues. In the developing forebrain, cerebellar primordium and spinal cord, strictly expressed in postmitotic neurons.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex), as such plays a role in remodeling mononucleosomes in an ATP-dependent fashion, and is required for postmitotic neural development and dendritic outgrowth. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. ACTL6B/BAF53B is not essential for assembly of the nBAF complex but is required for targeting the complex and CREST to the promoter of genes essential for dendritic growth. Essential for neuronal maturation and dendrite development (By similarity).|||Mice have lethal defects in neuronal development, including defects in activity-dependent dendritic outgrowth.|||Nucleus|||Restricted to the brain and peripheral nervous tissue (at protein level). Present in virtually all neurons in the cerebral neocortex (layers II-VI), hippocampus (CA1-CA3 region and dentate gyrus), cerebellum (molecular, granular and Purkinje cell layers), spinal cord (dorsally and ventrally), dorsal root ganglion, retina and the olfactory bulb (mitral and granule cell layers). Expressed specifically in postmitotic neurons (at protein level). http://togogenome.org/gene/10090:Sstr5 ^@ http://purl.uniprot.org/uniprot/O08858 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in adult brain but not in liver, heart, spleen, or kidney.|||Heterodimer with SSTR2. Heterodimerization with SSTR2 increases cell growth inhibition activity of SSTR2 (By similarity).|||Palmitoylated at Cys-319 by ZDHHC5, but not ZDHHC8. Palmitoylation creates an additional intracellular loop which is thought to be important for efficient coupling to G-proteins and may target the protein to lipid rafts.|||Receptor for somatostatin-28. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition activity of SSTR2 following heterodimerization. http://togogenome.org/gene/10090:Nufip1 ^@ http://purl.uniprot.org/uniprot/Q9QXX8 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds RNA.|||Expressed in the brain; in neurons and not in glial cells.|||Interacts with FMR1 (PubMed:10556305). Interacts with ZNHIT3 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Pigu ^@ http://purl.uniprot.org/uniprot/Q3TAA8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGU family.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Avl9 ^@ http://purl.uniprot.org/uniprot/Q80U56 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AVL9 family.|||Functions in cell migration.|||Membrane|||Recycling endosome http://togogenome.org/gene/10090:Txnrd1 ^@ http://purl.uniprot.org/uniprot/Q9JMH6 ^@ Cofactor|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.|||Binds 1 FAD per subunit.|||Cytoplasm|||Homodimer.|||ISGylated.|||Reduces disulfideprotein thioredoxin (Trx) to its dithiol-containing form. Homodimeric flavoprotein involved in the regulation of cellular redox reactions, growth and differentiation. Contains a selenocysteine residue at the C-terminal active site that is essential for catalysis. Also has reductase activity on hydrogen peroxide (H2O2).|||The thioredoxin reductase active site is a redox-active disulfide bond. The selenocysteine residue is also essential for catalytic activity. http://togogenome.org/gene/10090:Hnrnpf ^@ http://purl.uniprot.org/uniprot/Q9Z2X1 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state (By similarity).|||Identified in the spliceosome C complex. Interacts with AGO1, AGO2, TBP and TXNL4/DIM1 (By similarity).|||Sumoylated.|||The N-terminal RRM domains are responsible for recognizing the G-tract of BCL-X RNA.|||nucleoplasm http://togogenome.org/gene/10090:Or5m3b ^@ http://purl.uniprot.org/uniprot/Q8VFK5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Malsu1 ^@ http://purl.uniprot.org/uniprot/Q9CWV0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial ribosome large subunit (39S) via interaction with MRPL12 and/or MRPL14. The interaction generates steric hindrance that is expected to prevent premature association of the 28S and 39S ribosomal subunits. Identified in a complex composed of MALSU1, MIEF1 upstream open reading frame protein and NDUFAB1; within the trimeric complex, MIEF1 upstream open reading frame protein functions as a bridging scaffold that interacts with MALSU1 on one side, and with NDUFAB1 on the other side. Interacts with MRPL12 and MRPL14.|||Belongs to the Iojap/RsfS family.|||Mitochondrion matrix|||Required for normal mitochondrial ribosome function and mitochondrial translation. May play a role in ribosome biogenesis by preventing premature association of the 28S and 39S ribosomal subunits. Interacts with mitochondrial ribosomal protein uL14m (MRPL14), probably blocking formation of intersubunit bridge B8, preventing association of the 28S and 39S ribosomal subunits. Addition to isolated mitochondrial ribosomal subunits partially inhibits translation, probably by interfering with the association of the 28S and 39S ribosomal subunits and the formation of functional ribosomes. May also participate in the assembly and/or regulation of the stability of the large subunit of the mitochondrial ribosome. May function as a ribosomal silencing factor. http://togogenome.org/gene/10090:Rcn2 ^@ http://purl.uniprot.org/uniprot/Q8BP92 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CREC family.|||Endoplasmic reticulum lumen|||Not known. Binds calcium (By similarity). http://togogenome.org/gene/10090:Palmd ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J0|||http://purl.uniprot.org/uniprot/Q3UVT7|||http://purl.uniprot.org/uniprot/Q9JHU2 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paralemmin family.|||Cytoplasm|||Interacts with GLUL.|||Phosphorylated.|||Ubiquitous. Expressed at highest levels in the heart and lung.|||dendrite|||dendritic spine http://togogenome.org/gene/10090:Usp43 ^@ http://purl.uniprot.org/uniprot/Q8BUM9 ^@ Function|||Similarity ^@ Belongs to the peptidase C19 family.|||May recognize and hydrolyze the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins (By similarity). http://togogenome.org/gene/10090:Brat1 ^@ http://purl.uniprot.org/uniprot/Q8C3R1 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||High levels detected in the cortex and much lower levels detected in the cerebellum, spinal cord and lung (at protein level).|||Interacts with BRCA1 and ATM. Interacts with MTOR, RPTOR, NDFIP1, SMC1A and PRKDC.|||Involved in DNA damage response; activates kinases ATM, SMC1A and PRKDC by modulating their phosphorylation status following ionizing radiation (IR) stress. Plays a role in regulating mitochondrial function and cell proliferation (By similarity). Required for protein stability of MTOR and MTOR-related proteins, and cell cycle progress by growth factors (PubMed:25657994).|||Nucleus|||Ubiquitinated by NEDD4, NEDD4L and ITCH; mono- and polyubiquitinated forms are detected. http://togogenome.org/gene/10090:Tmem18 ^@ http://purl.uniprot.org/uniprot/Q3TUD9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM18 family.|||Cytoplasm|||Forms homooligomers, independently of the DNA-binding domain.|||Nucleus membrane|||Transcription repressor. Sequence-specific ssDNA and dsDNA binding protein, with preference for GCT end CTG repeats. Cell migration modulator which enhances the glioma-specific migration ability of neural stem cells (NSC) and neural precursor cells (NPC) (By similarity). http://togogenome.org/gene/10090:Mettl2 ^@ http://purl.uniprot.org/uniprot/Q8BMK1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METL family.|||Cytoplasm|||Mice were born with normal Mendelian ratio without developmental defects (PubMed:28655767). Cells show reduced N(3)-methylcytidine modification in tRNA fractions (PubMed:28655767).|||Monomer. Interacts with DALRD3.|||S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Thr)(UGU) and tRNA(Arg)(CCU) (PubMed:28655767). N(3)-methylcytidine methylation by METTL2 requires the N6-threonylcarbamoylation of tRNA (t6A37) by the EKC/KEOPS complex as prerequisite (By similarity). http://togogenome.org/gene/10090:Brd1 ^@ http://purl.uniprot.org/uniprot/G5E8P1 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Component of some HBO1 complexes composed of KAT7/HBO1, MEAF6, ING4 and BRD1/BRPF2 (PubMed:21753189). Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3 (By similarity). Interacts (via PHD-type zinc finger domain) with unmodified histone H3 (By similarity). Interacts (via PWWP domain) with dimethylated and trimethylated 'Lys-79' on histone H3 (By similarity).|||Embryos die at mid-gestation because of anemia and impaired fetal liver erythropoiesis.|||Nucleus|||Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, that acts as a regulator of hematopoiesis (PubMed:21753189). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby promoting erythroid differentiation (PubMed:21753189). http://togogenome.org/gene/10090:Higd1a ^@ http://purl.uniprot.org/uniprot/Q1XG81|||http://purl.uniprot.org/uniprot/Q9JLR9 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ Associates with cytochrome c oxidase (COX, complex IV); proposed complex component. Also associates with respiratory chain supercomplexes (By similarity).|||By hypoxia.|||Mitochondrion inner membrane|||Mitochondrion membrane|||Proposed subunit of cytochrome c oxidase (COX, complex IV), which is the terminal component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. May play a role in the assembly of respiratory supercomplexes (By similarity). http://togogenome.org/gene/10090:Mmp3 ^@ http://purl.uniprot.org/uniprot/P28862|||http://purl.uniprot.org/uniprot/Q3UFJ0|||http://purl.uniprot.org/uniprot/Q922W6 ^@ Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Binds 4 Ca(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||MMP3-deficient mice have impaired antiviral cytokine and chemokine responses at early stage of viral infections (PubMed:35940311). In addition, neuronal degeneration, microglial activation, and superoxide generation are largely attenuated in these mutant mice (PubMed:17116747).|||Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates different molecules including growth factors, plasminogen or other matrix metalloproteinases such as MMP9. Once released into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin cascade signaling pathway. Acts also intracellularly. For example, in dopaminergic neurons, gets activated by the serine protease HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration by mediating microglial activation and alpha-synuclein/SNCA cleavage (PubMed:17116747). In addition, plays a role in immune response and possesses antiviral activity against various viruses (PubMed:35940311). Mechanistically, translocates from the cytoplasm into the cell nucleus upon virus infection to influence NF-kappa-B activities (PubMed:35940311).|||Present in unfertilized eggs and at the zygote and cleavage stages. Levels increase at the blastocyst stage and with endoderm differentiation.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||extracellular matrix http://togogenome.org/gene/10090:Ccl27a ^@ http://purl.uniprot.org/uniprot/Q9Z1X0 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Chemotactic factor that attracts skin-associated memory T-lymphocytes. May play a role in mediating homing of lymphocytes to cutaneous sites. May play a role in cell migration during embryogenesis. Nuclear forms may facilitate cellular migration by inducing cytoskeletal relaxation. Binds to CCR10.|||Expressed during development.|||Isoform 1 is predominantly expressed in placenta and weakly in skin. Isoform 2 is predominantly expressed in testes and brain, weakly in kidney and liver and even lower in heart and muscle. Low expression of both isoforms in other tissues.|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Monomer, dimer, and tetramer. Heparin avidly promotes oligomerization. Interacts with TNFAIP6 (via Link domain).|||Nucleus|||Secreted http://togogenome.org/gene/10090:H2ab2 ^@ http://purl.uniprot.org/uniprot/S4R1M3 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Fermt3 ^@ http://purl.uniprot.org/uniprot/Q3TEE6|||http://purl.uniprot.org/uniprot/Q8K1B8 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the kindlin family.|||Interacts with ITGB1, ITGB2 and ITGB3 (via cytoplasmic tails).|||Mice suffer from fatal anemia, caused by severe bleeding and erythrocytopenia. Mice also show markedly reduced size and cellularity. Platelets cannot activate integrins despite normal Talin (Tln1) expression.|||Plays a central role in cell adhesion in hematopoietic cells (By similarity). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (PubMed:18278053). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234461). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (PubMed:18278053).|||Specifically expressed in hematopoietic cells.|||The FERM domain is not correctly detected by PROSITE or Pfam techniques because it contains the insertion of a PH domain.|||podosome http://togogenome.org/gene/10090:Gper1 ^@ http://purl.uniprot.org/uniprot/Q8BMP4 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle membrane|||Early endosome|||Endoplasmic reticulum membrane|||Expressed in brain, heart, spleen, preadipocytes, mature adipocytes and primary hippocampal neurons. Expressed in neurons of the hippocampus, hypothalamic paraventricular nucleus (PVH), supraoptic nucleus (SON) and the median eminence. Expressed in the nucleus ambiguous (at protein level). Expressed in brain, pituitary gland, adrenal medulla, renal pelvis, ovary, endothelial cells, visceral fat tissues and islets of Langerhans.|||G-protein coupled estrogen receptor that binds to 17-beta-estradiol (E2) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Stimulates cAMP production, calcium mobilization and tyrosine kinase Src inducing the release of heparin-bound epidermal growth factor (HB-EGF) and subsequent transactivation of the epidermal growth factor receptor (EGFR), activating downstream signaling pathways such as PI3K/Akt and ERK/MAPK. Mediates pleiotropic functions among others in the cardiovascular, endocrine, reproductive, immune and central nervous systems. Has a role in cardioprotection by reducing cardiac hypertrophy and perivascular fibrosis in a RAMP3-dependent manner. Regulates arterial blood pressure by stimulating vasodilation and reducing vascular smooth muscle and microvascular endothelial cell proliferation. Plays a role in blood glucose homeostasis contributing to the insulin secretion response by pancreatic beta cells. Triggers mitochondrial apoptosis during pachytene spermatocyte differentiation. Stimulates uterine epithelial cell proliferation. Enhances uterine contractility in response to oxytocin. Contributes to thymic atrophy by inducing apoptosis. Attenuates TNF-mediated endothelial expression of leukocyte adhesion molecules. Promotes neuritogenesis in developing hippocampal neurons. Plays a role in acute neuroprotection against NMDA-induced excitotoxic neuronal death. Increases firing activity and intracellular calcium oscillations in luteinizing hormone-releasing hormone (LHRH) neurons. Inhibits early osteoblast proliferation at growth plate during skeletal development. Inhibits mature adipocyte differentiation and lipid accumulation. Involved in the recruitment of beta-arrestin 2 ARRB2 at the plasma membrane in epithelial cells. Functions also as a receptor for aldosterone mediating rapid regulation of vascular contractibility through the PI3K/ERK signaling pathway. Involved in cancer progression regulation. Stimulates cancer-associated fibroblast (CAF) proliferation by a rapid genomic response through the EGFR/ERK transduction pathway. Associated with EGFR, may act as a transcription factor activating growth regulatory genes (c-fos, cyclin D1). Promotes integrin alpha-5/beta-1 and fibronectin (FN) matrix assembly in breast cancer cells.|||Golgi apparatus membrane|||Interacts with RAMP3. Interacts with KRT7 and KRT8. Interacts with EGFR; the interaction increases after agonist-induced stimulation in cancer-associated fibroblasts (CAF). Interacts with EGFR and ESR1. Interacts (via C-terminus tail motif) with DLG4 (via N-terminus tandem pair of PDZ domains); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner (By similarity). Homodimer (Probable). Heterodimer; heterodimerizes with other G-protein-coupled receptor (GPCRs) like CRHR1, HTR1A and PAQR8.|||Mitochondrion membrane|||N-glycosylated.|||Nucleus|||Postsynaptic density|||Recycling endosome|||Strong variations in phenotypes, probably depending on the distinct targeting strategies, genetic background and experimental conditions used in the different experiments. According to PubMed:18063692, mice are viable and fertile and do not display any gross physical, immunological, reproductive and neurological abnormalities, but show 17-beta-estradiol (E2)-induced alleviated thymic atrophy. According to PubMed:20734455, male mice display increased body size, femur length, bone mass and cell proliferative activity within the growth plate. According to PubMed:18845638, female mice, but not male, show reduced body weight and skeletal growth, hyperglycemia, impaired glucose tolerance with reduced glucose-stimulated insulin release and increased blood pressure. According to PubMed:19179659 mice show increased body weight, visceral adiposity, vascular tone and blood pressure. No visible phenotype according to PubMed:18799753.|||Ubiquitinated; ubiquitination occurs at the plasma membrane and leads to proteasome-mediated degradation.|||Up-regulated during adipogenesis.|||axon|||cytoskeleton|||dendrite|||dendritic spine membrane|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Zfp185 ^@ http://purl.uniprot.org/uniprot/Q62394 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ At 14.5 dpc, only expressed in mesenchymal cells. At 16.5 dpc expressed also in cells lining the vertebrae and tendons of the proximal tail. In late embryogenesis, expressed in mesenchymal cells adjacent to the distal limb bones (tibia and calcaneum), in tendons and in the connective tissue sheath (epimysium) surrounding the skeletal muscle. Also expressed in the epithelia of the epididymis of the testis.|||Expressed in skin, kidney, ovary, testis. Also expressed in brain, cartilage, heart, lung, spleen and thymus.|||May be involved in the regulation of cellular proliferation and/or differentiation.|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Rrp12 ^@ http://purl.uniprot.org/uniprot/Q3UJA1|||http://purl.uniprot.org/uniprot/Q6P5B0 ^@ Sequence Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RRP12 family.|||Intron retention.|||Nucleus membrane|||nucleolus http://togogenome.org/gene/10090:Kif13b ^@ http://purl.uniprot.org/uniprot/A0A286YCV9|||http://purl.uniprot.org/uniprot/E9Q4K7 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. http://togogenome.org/gene/10090:Adgrb2 ^@ http://purl.uniprot.org/uniprot/B1ASC0|||http://purl.uniprot.org/uniprot/Q8CGM1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoproteolytically processed at the GPS domain; this cleavage modulates receptor activity. Additionally, furin is involved in the cleavage at another site, in the middle of the extracellular domain, generating a soluble fragment.|||Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Deficient mice show significant resistance to depression after repeated stress in the social defeat test. Additionally, hippocampal cell proliferation in deficient mice is increased.|||Down-regulated after hypoxia.|||Glycosylated.|||Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked. Interacts with GABPB2 (PubMed:16412436). Interacts (via carboxy-terminus) with TAX1BP3. Interacts with GNAZ (By similarity). Interacts with SH3GL2 (PubMed:28891236).|||Membrane|||Orphan G-protein coupled receptor involved in cell adhesion and probably in cell-cell interactions. Activates NFAT-signaling pathway, a transcription factor, via the G-protein GNAZ. Involved in angiogenesis inhibition (PubMed:12218411).|||Receptor activity is regulated by proteolytic processing. The long N-terminal has a an inhibitory effect on the constitutive signaling activity. Removal of the N-terminal region induces an increase of the receptor activity.|||Secreted|||Specifically expressed in the brain. The peak level in the brain is observed 10 days after birth.|||Ubiquitous in embryonic tissues, but expression is acutely down-regulated after birth, except in the brain, to a level that is maintained throughout adulthood. http://togogenome.org/gene/10090:Vps52 ^@ http://purl.uniprot.org/uniprot/Q8C754 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD. Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane.|||Belongs to the VPS52 family.|||Component of the Golgi-associated retrograde protein (GARP) complex, also called VFT (VPS fifty-three) complex, composed of VPS51, VPS52, VPS53 and VPS54. Component of the endosome-associated retrograde protein (EARP) complex, composed of VPS51, VPS52, VPS53 and VPS50/Syndetin. EIPR1 interacts with both EARP and GARP complexes and mediates the recruitment of the GARP complex to the trans-Golgi network. Interacts with RAB6A and STX10. Interacts with BLTP3B.|||Endosome membrane|||Recycling endosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Mtfmt ^@ http://purl.uniprot.org/uniprot/Q3V021|||http://purl.uniprot.org/uniprot/Q9D799 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Fmt family.|||Composed of an N- and a C-terminal domain. The N-terminal domain carries the tetrahydrofolate (THF)-binding site and the C-terminal domain is presumably involved in positioning the Met-tRNA substrate for the formylation reaction.|||Methionyl-tRNA formyltransferase that formylates methionyl-tRNA in mitochondria and is crucial for translation initiation.|||Mitochondrion http://togogenome.org/gene/10090:Pramel47 ^@ http://purl.uniprot.org/uniprot/D3YUK0 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Gja8 ^@ http://purl.uniprot.org/uniprot/P28236|||http://purl.uniprot.org/uniprot/Q548M7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels. Forms heteromeric channels with GJA3.|||Belongs to the connexin family. Alpha-type (group II) subfamily.|||Cell membrane|||Detected in eye lens (at protein level). Eye lens.|||Membrane|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||Structural component of eye lens gap junctions (PubMed:1325220). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (By similarity). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:1325220).|||gap junction http://togogenome.org/gene/10090:Vmn2r29 ^@ http://purl.uniprot.org/uniprot/L7N2D4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Irx4 ^@ http://purl.uniprot.org/uniprot/Q9QY61 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TALE/IRO homeobox family.|||Expressed in the developing central nervous system, skin, and vibrissae, but predominantly expressed in the cardiac ventricles of the developing heart. Not expressed in the developing metanephric kidney or adult kidney.|||Interacts with the vitamin D receptor VDR but doesn't affect its transactivation activity.|||Likely to be an important mediator of ventricular differentiation during cardiac development.|||Nucleus http://togogenome.org/gene/10090:Zbed6 ^@ http://purl.uniprot.org/uniprot/D2EAC2|||http://purl.uniprot.org/uniprot/G0LE24 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Encoded by an exapted DNA transposon located in an intron of the Zc3h11a gene.|||Expressed in fetal muscle tissues at 12.5 dpc.|||Expressed in pancreatic islet cells and weakly expressed in surrounding exocrine tissues (at protein level) (PubMed:24043816). Expressed in muscle and brain (at protein level) (PubMed:20016685). Shows broad tissue distribution with expression detected in brain, stomach, intestine, heart, kidney, liver, lung, skeletal muscle, ovary, spleen, tail and testis (PubMed:20016685).|||Increase in body weight of mice at 20 weeks of age, at 23 weeks of age only female mice show an increase in body weight and lean mass as a result of an increase in muscle mass (PubMed:29440408). Increase in the weight of kidneys in both male and female adult mice with an increase in the weight of the liver in female mice (PubMed:29440408). Decrease in plasma insulin levels with an increase in blood glucose clearance and increased reliance on carbohydrates as a fuel source in male mice (PubMed:29440408). Increase in serum IGF2 protein levels in adult mice (PubMed:29440408). Increase in expression of IGF2, PGAP6/TMEM8, and ENHO in skeletal muscle (PubMed:29440408). Expression of ENHO and PIANP also increases in the heart and kidney, in addition to an increase of PGAP6/TMEM8 expression in the heart (PubMed:29440408). Significant increase in expression of PGAP6/TMEM8 and ENHO in fetal muscle tissue with a small marginal increase in IGF2 expression (PubMed:29440408).|||Nucleus|||Transcriptional repressor which binds to the consensus sequence 5'-GCTCGC-3', transcription regulation may be tissue-specific (PubMed:20016685, PubMed:20134481, PubMed:24043816, PubMed:29440408, PubMed:32557799). Regulates the expression of target genes such as: IGF2, PGAP6/TMEM8, ENHO, and PIANP (PubMed:20016685, PubMed:20134481, PubMed:24043816, PubMed:29440408, PubMed:32557799). Acts as a transcriptional repressor of growth factor IGF2, thereby negatively regulating postnatal growth of muscles and internal organs, especially in females (PubMed:20016685, PubMed:29440408, PubMed:32557799). Negatively regulates myoblast differentiation and myoblast mitochondrial activity via its regulation of IGF2 transcription (PubMed:32557799). Negatively regulates the cell cycle of myoblasts, potentially via transcriptional regulation of the E2F family of transcription factors such as: E2F1 and E2F2 (PubMed:20016685, PubMed:32557799). Positively regulates the cell cycle and survival of pancreatic beta cells (PubMed:24043816). Binds to the CDH2 gene and may directly repress CDH2 transcription (PubMed:26750727). Probably by controlling CDH2 expression, regulates pancreatic beta cell adhesion, and formation of cell-to-cell junctions between pancreatic beta cells and neural crest stem cells (PubMed:26750727). May also play a role in embryonic beta cell differentiation (PubMed:24043816). May play a role in insulin sensitivity and glucose clearance (PubMed:29440408).|||nucleolus http://togogenome.org/gene/10090:Serpinb3d ^@ http://purl.uniprot.org/uniprot/Q6UKZ0 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Ppp1r35 ^@ http://purl.uniprot.org/uniprot/Q9D8C8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP1R35 family.|||During centriole duplication, plays a role in the centriole elongation by promoting the recruitment of the microtubule-binding elongation machinery through its interaction with TTTN, leading to the centriole to centrosome conversion (By similarity). In addition may play a role in the primary cilia assembly (PubMed:32628936).|||Expressed throughout much of the embryo at 7.5 dpc, in mesoderm and ectoderm-derived structures at 8.5 dpc, and throughout much of the embryo at 9.5 dpc but is absent in the extra-embryonic visceral endoderm (VE) at all stages.|||Interacts with PPP1CA; this interaction mediates the PPP1CA phosphatase activity inhibition. Interacts with RTTN; this interaction allows the mutual recruitment to the centriole.|||Mice homozygous embryos for the Ppp1r35 gene are lethal during early embryogenesis (PubMed:32628936). Homozygous embryos are capable of initiating and completing gastrulation as well as specifying the anterior/posterior and the dorsal/ventral axis, but exhibit a developmental delays which are the result in the failure to progress past 8.5 dpc to 9.0 dpc (PubMed:32628936).|||centriole|||centrosome http://togogenome.org/gene/10090:Or7g21 ^@ http://purl.uniprot.org/uniprot/Q8VFJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slf2 ^@ http://purl.uniprot.org/uniprot/E9Q839 ^@ Similarity ^@ Belongs to the FAM178 family. http://togogenome.org/gene/10090:F5 ^@ http://purl.uniprot.org/uniprot/O88783 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated protein C inactivates factor V and factor Va by proteolytic degradation.|||Belongs to the multicopper oxidase family.|||Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.|||Domain B contains 32 X 9 AA tandem repeats, and 1 X 17 AA repeats.|||Factor Va, the activated form of factor V, is composed of a heavy chain and a light chain, non-covalently bound. The interaction between the two chains is calcium-dependent. Forms heterodimer with SERPINA5 (By similarity).|||Inhibited by SERPINA5.|||Secreted|||Sulfation is required for efficient thrombin cleavage and activation and for full procoagulant activity.|||Thrombin activates factor V proteolytically to the active cofactor, factor Va (formation of a heavy chain at the N-terminus and a light chain at the C-terminus). http://togogenome.org/gene/10090:Igf2bp2 ^@ http://purl.uniprot.org/uniprot/Q5SF07 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRM IMP/VICKZ family.|||Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Interacts with HNRPD. Interacts with IGF2BP1. Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1.|||Cytoplasm|||Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules.|||Expressed in oocytes, granulosa cells of small and growing follicles and Leydig cells of the testis (at protein level). Expressed in testis and ovary.|||Expressed in zygotes and blastocysts (at protein level). Expressed in gonads at 12.5, 14.5 and 16.5 dpc (at protein level). Expressed during fetal development at 12.5, 14.5 and 17.5 dpc and declining towards birth.|||Nucleus|||P-body|||RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation (By similarity). Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (By similarity). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs. Binding is isoform-specific. Binds to beta-actin/ACTB and MYC transcripts (By similarity). Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (By similarity).|||Stress granule http://togogenome.org/gene/10090:Gpn1 ^@ http://purl.uniprot.org/uniprot/Q4VAB2|||http://purl.uniprot.org/uniprot/Q8VCE2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GPN-loop GTPase family.|||Binds to RNA polymerase II.|||Cytoplasm|||Heterodimer with GPN3. Binds to RNA polymerase II (RNAPII). Interacts directly with RNAPII subunits RPB4 and RPB7 and the CTD of RPB1. Interacts with XPA.|||Nucleus|||Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import.|||Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import. Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding proteins, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. May be involved in nuclear localization of XPA. http://togogenome.org/gene/10090:Aass ^@ http://purl.uniprot.org/uniprot/Q3UEQ9|||http://purl.uniprot.org/uniprot/Q99K67 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Bifunctional enzyme that catalyzes the first two steps in lysine degradation.|||Highly expressed in kidney and liver, very low expression is seen in heart, brain, spleen, lung, skeletal muscle and testis.|||Homotetramer.|||In the C-terminal section; belongs to the saccharopine dehydrogenase family.|||In the N-terminal section; belongs to the AlaDH/PNT family.|||Induced by starvation.|||Mitochondrion|||The N-terminal and the C-terminal domains contain respectively the lysine ketoglutarate reductase and saccharopine dehydrogenase activity. http://togogenome.org/gene/10090:Hba-a1 ^@ http://purl.uniprot.org/uniprot/Q91VB8 ^@ Similarity ^@ Belongs to the globin family. http://togogenome.org/gene/10090:Pot1a ^@ http://purl.uniprot.org/uniprot/Q91WC1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the telombin family.|||Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. Is a component of the double-stranded telomeric DNA-binding TRF1 complex which is involved in the regulation of telomere length by cis-inhibition of telomerase. Also acts as a single-stranded telomeric DNA-binding protein and thus may act as a downstream effector of the TRF1 complex and may transduce information about telomere maintenance and/or length to the telomere terminus. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Binds to two or more telomeric single-stranded 5'-TTAGGG-3' repeats (G-strand) and with high specificity to a minimal telomeric single-stranded 5'-TAGGGTTAG-3' sequence. Binds telomeric single-stranded sequences internally or at proximity of a 3'-end. Its activity is TERT dependent but it does not increase TERT activity (By similarity).|||Homodimer or homooligomer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP, ACD and POT1. Binds single-stranded telomeric DNA as a monomer. Associated component of the telomerase holoenzyme complex. Found in a complex with TERF1, TINF2 and TNKS1. Interacts with TNKS1. Forms heterodimers with ACD. Identified in a complex with ACD and single-stranded telomeric DNA.|||Nucleus|||telomere http://togogenome.org/gene/10090:Ajap1 ^@ http://purl.uniprot.org/uniprot/A2ALI5 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Basolateral cell membrane|||Forms a complex with CDH1 and CTNNB1; interacts directly with CTNNB1 (By similarity). Interacts with AP1M2 and isoform 2 of BSG/CD147 (By similarity).|||Plays a role in cell adhesion and cell migration.|||adherens junction http://togogenome.org/gene/10090:Cog1 ^@ http://purl.uniprot.org/uniprot/Q9Z160 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG1 family.|||Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.|||Golgi apparatus membrane|||Required for normal Golgi function. http://togogenome.org/gene/10090:Erbb2 ^@ http://purl.uniprot.org/uniprot/P70424 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Ligand-binding increases phosphorylation on tyrosine residues. Signaling via SEMA4C promotes phosphorylation at Tyr-1249. Dephosphorylated by PTPN12.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.|||Cell membrane|||Early endosome|||Expressed predominantly in uterine epithelial cells. In the muscle, expression localizes to the synaptic sites of muscle fibers.|||Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1197. Interacts with PLXNB1. Interacts (when phosphorylated on Tyr-1249) with MEMO1. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1140) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1249) with ERBIN. Interacts with KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA194 and ACTB. Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner. Interacts with HSP90AA1 and HSP90AB1 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (By similarity). Interacts with SRC (PubMed:7542762). Interacts with MYOC (PubMed:23897819). Interacts with PRKCABP (PubMed:11278603). Interacts with SORL1; this interaction regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulates ERBB2-mediated signaling (By similarity). Interacts with SH3BGRL (By similarity).|||In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth (By similarity).|||Nucleus|||On days 1-4 of pregnancy, ERBB2 is detected primarily in epithelial cells, the day 1 uterus showing the highest accumulation. On day 5, the epithelium and the decidualizing stromal cells around the implanting blastocyst exhibit accumulation of this receptor. On days 6-8, the expression persists in the epithelium at both the implantation and interimplantation sites in addition to modest levels in the secondary decidual zone. On days 7 and 8, accumulation is also prominent in the trophoblastic giant cells.|||Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity).|||perinuclear region|||ruffle membrane http://togogenome.org/gene/10090:Ube2dnl1 ^@ http://purl.uniprot.org/uniprot/A2AFH1 ^@ Similarity ^@ Belongs to the ubiquitin-conjugating enzyme family. http://togogenome.org/gene/10090:Kif3a ^@ http://purl.uniprot.org/uniprot/B1AQZ2|||http://purl.uniprot.org/uniprot/P28741|||http://purl.uniprot.org/uniprot/Q3TET1|||http://purl.uniprot.org/uniprot/Q3UI47 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin II subfamily.|||Expressed almost exclusively in adult brain tissue (mainly in the cerebellar granular layer) within a single type of neuronal cell.|||Heterodimer of KIF3A and KIF3B (PubMed:7559760). Interacts with CIMAP3 (PubMed:20643351). Interacts with CLN3 (By similarity). Interacts with DCTN1 (PubMed:23386061). Interacts with FLCN (By similarity). Interacts with AP3B1 (By similarity).|||Microtubule-based anterograde translocator for membranous organelles. Plus end-directed microtubule sliding activity in vitro. Plays a role in primary cilia formation (PubMed:21670265). Plays a role in centriole cohesion and subdistal appendage organization and function. Regulates the formation of the subdistal appendage via recruitment of DCTN1 to the centriole. Also required for ciliary basal feet formation and microtubule anchoring to mother centriole (PubMed:23386061).|||centriole|||cilium|||cytoskeleton http://togogenome.org/gene/10090:Defb14 ^@ http://purl.uniprot.org/uniprot/Q7TNV9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Ostn ^@ http://purl.uniprot.org/uniprot/P61364 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Osteocrin family.|||Expressed during matrix production and maturation. Also expressed during myocyte differentiation.|||Expressed in skeletal muscle and to a much lesser extent in bone, brown adipose tissue, spleen and testis (PubMed:14523025, PubMed:15044443, PubMed:26668395). Not expressed in neurons (PubMed:27830782).|||Hormone that acts as a ligand for natriuretic peptide receptor NPR3/NPR-C and promotes bone growth and physical endurance in muscle. Acts as a regulator of osteoblast differentiation and bone growth by binding to natriuretic peptide receptor NPR3/NPR-C, thereby preventing binding between NPR3/NPR-C and natriuretic peptides, leading to increase cGMP production (PubMed:14523025, PubMed:17951249). Required to enhance physical endurance: induced following physical exercise in muscle and promotes cGMP production, probably by interacting with NPR3/NPR-C (PubMed:26668395). May act as an autocrine and paracrine factor linked to glucose metabolism in skeletal muscle (PubMed:15044443).|||Interacts with NPR3.|||Is regulated by nutritional changes (PubMed:15044443). Is up-regulated dose-dependently by insulin (PubMed:15044443). Is down-regulated dose-dependently by forskolin (PubMed:15044443). Induced in muscle following physical exercise (PubMed:26668395).|||Mice grow normally and do not display any visible phenotype but show reduced physical endurance (PubMed:26668395). Mice do not show skeletal deformities, differences in bone density, growth abnormalities, blood pressure nor body composition changes (PubMed:26668395).|||Secreted|||This protein-coding gene has been repurposed in primates, with the presence of a new enhancer sequence that drives expression in brain in response to sensory experience (PubMed:27830782). http://togogenome.org/gene/10090:Tex13c1 ^@ http://purl.uniprot.org/uniprot/D3YU32 ^@ Similarity ^@ Belongs to the TEX13 family. http://togogenome.org/gene/10090:Or10g7 ^@ http://purl.uniprot.org/uniprot/E9Q985 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nat14 ^@ http://purl.uniprot.org/uniprot/Q8BVG8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the camello family.|||May act as a transcription factor regulating the expression of coproporphyrinogen oxidase by binding to a promoter regulatory element.|||Membrane|||Probable acetyltransferase that binds the 5'-GGACTACAG-3' sequence of coproporphyrinogen oxidase promoter. Able to activate transcription of a reporter construct in vitro (By similarity).|||Probable acetyltransferase. http://togogenome.org/gene/10090:Ndufs5 ^@ http://purl.uniprot.org/uniprot/Q99LY9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I NDUFS5 subunit family.|||Contains two C-X9-C motifs that are predicted to form a helix-coil-helix structure, permitting the formation of intramolecular disulfide bonds.|||Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme.|||Mitochondrion inner membrane|||Mitochondrion intermembrane space http://togogenome.org/gene/10090:Syt12 ^@ http://purl.uniprot.org/uniprot/Q920N7 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptotagmin family.|||Detected at low levels in the brain at postnatal day 5 (at protein level) (PubMed:17190793). Expression in the brain is increased by postnatal days 9 and 10, and continues to increase at postnatal days 15 and 20 (at protein level) (PubMed:17190793).|||Expressed in the brain, specifically by neurons in the hippocampus, and in the adrenal medulla (at protein level).|||Homodimer (By similarity). Can also form heterodimers (By similarity). Interacts with SYT1 (By similarity).|||No measurable change in basal synaptic strength or short-term neuronal plasticity (PubMed:23739973). Neurons from the CA3 hippocampal region exhibit an impairment of cAMP-dependent long-term potentiation in mossy-fiber synapses (PubMed:23739973).|||Phosphorylation of Ser-97 is required for mossy-fiber long-term potentiation.|||Synaptic vesicle phosphoprotein that enhances spontaneous neurotransmitter release but does not effect induced neurotransmitter release (By similarity). Unlike other synaptotagmins, it does not bind Ca(2+) or phospholipids (By similarity). Essential for mossy-fiber long-term potentiation in the hippocampus (PubMed:23739973).|||Unlike classical synaptotagmins, lacks Ca(2+)-binding sequences and does not bind phospholipids.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Dzip1 ^@ http://purl.uniprot.org/uniprot/Q8BMD2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DZIP C2H2-type zinc-finger protein family.|||Cytoplasm|||Expressed in testis and undifferentiated ES cells.|||Interacts with DAZ1 (By similarity). Interacts with the BBSome; recruits the BBSome to centriolar satellites of the cilium (PubMed:27979967). Interacts with PCM1; localizes DZIP1 and the associated BBSome to centriolar satellites (PubMed:27979967). Interacts with RAB8A (GDP-bound inactive form); recruits RAB8A to the basal body of the cilium and prevents its inhibition by GDI2 (PubMed:25860027). Interacts with GDI2; negatively regulates the interaction of GDI2 with GDP-bound RAB8A (PubMed:25860027). Interacts with GLI3; retains GLI3 within the cytoplasm (PubMed:23955340). Interacts with CEP164 (PubMed:23955340). Interacts with IFT88 (PubMed:23955340).|||Male animals were all infertile. Few spermatozoa were collected from the epididymides of the mutant, and no motile spermatozoa were seen. Light microscopy of the mutant spermatozoa showed severe morphologic abnormalities, primarily absent flagella as well as residual cytoplasm and abnormal heads.|||Molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body (PubMed:23955340, PubMed:25860027, PubMed:31118289, PubMed:32051257). At the exit of mitosis, localizes to the basal body and ciliary base of the forming primary cilium where it recruits and activates RAB8A to direct vesicle-mediated transport of proteins to the cilium (PubMed:25860027). Also recruits the BBSome, a complex involved in cilium biogenesis, by bridging it to PCM1 at the centriolar satellites of the cilium (PubMed:27979967). It is also required for the recruitment to the cilium basal body of the intraflagellar transport (IFT) machinery as well as the ciliary appendage proteins CEP164 and NINEIN (PubMed:23955340). Functions as a regulator of Hedgehog signaling both through its role in cilium assembly but also probably through its ability to retain GLI3 within the cytoplasm (PubMed:23955340). It is involved in spermatogenesis through its role in organization of the basal body and assembly of the sperm flagellum (PubMed:32051257). Also indirectly involved in heart development through its function in ciliogenesis (PubMed:31118289).|||Nucleus|||Nucleus speckle|||Phosphorylation at Ser-210 by PLK1 before mitosis prevents interaction with PCM1 and localization to centriolar satellites. Thereby, it negatively regulates the localization of the BBSome to centriolar satellites (PubMed:27979967). Undergoes postmitotic phosphorylation at Ser-520 by GSK3B. That phosphorylated form of DZIP1 interacts with GDI2, disrupting its interaction with RAB8A, leading to RAB8A activation and localization to the cilium where it mediates protein transport and participates to cilium biogenesis (PubMed:25860027).|||centriolar satellite|||centriole|||cilium basal body http://togogenome.org/gene/10090:Or14j3 ^@ http://purl.uniprot.org/uniprot/Q923Q8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp4x1 ^@ http://purl.uniprot.org/uniprot/Q6A152 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase that selectively catalyzes the epoxidation of the last double bond of the arachidonoyl moiety of anandamide, potentially modulating endocannabinoid signaling. Has no hydroxylase activity toward various fatty acids, steroids and prostaglandins. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Expressed in brain and aorta. In the brain, expressed in the Purkinje cells of the cerebellum, pyramidal neurons in the dentate gyrus of the hippocampus, cortical forebrain neurons and those of brain stem nuclei (at protein level). In addition to neurons, also expressed in cerebral vascular endothelial cells (at protein level). Also expressed in epithelial cells of the choroid plexus (at protein level). Hardly detectable in heart, lung, kidney and spleen.|||Microsome membrane http://togogenome.org/gene/10090:Tmem210 ^@ http://purl.uniprot.org/uniprot/Q9D2F0 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Ube2b ^@ http://purl.uniprot.org/uniprot/A2RSE4|||http://purl.uniprot.org/uniprot/P63147 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA. Associates to the E3 ligase RAD18 to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. May be involved in neurite outgrowth.|||Belongs to the ubiquitin-conjugating enzyme family.|||Cell membrane|||Interacts with RAD18, UBR2 and WAC.|||Nucleus http://togogenome.org/gene/10090:Nol6 ^@ http://purl.uniprot.org/uniprot/Q8R5K4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NRAP family.|||Chromosome|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with RRP7A; required for NOL6 localization to nucleolus.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Ccn3 ^@ http://purl.uniprot.org/uniprot/Q64299 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCN family.|||Cytoplasm|||Expressed in large vessels including the ascending aorta, carotid arteries, and the thoracic aorta, in medium-sized vessels such as coronary arteries and small pulmonary veins and also in small vessels. In addition, also found to be present in the heart (at protein level) (PubMed:21063504). Expressed in astrocytes (at protein level) (PubMed:15213231). Detected in brain, bone, lung and muscle tissues (PubMed:20139355, PubMed:23653360). Expressed in skin, expression highly increases 5 days post-wounding, peaking on the 7th day to decline after 9 days (PubMed:15611078). Expressed in pancreatic ducts and beta-cell islets (PubMed:23705021).|||Expression is reduced in atherosclerosis progression.|||Immediate-early protein playing a role in various cellular processes including proliferation, adhesion, migration, differentiation and survival. Acts by binding to integrins or membrane receptors such as NOTCH1. Essential regulator of hematopoietic stem and progenitor cell function. Inhibits myogenic differentiation through the activation of Notch-signaling pathway. Inhibits vascular smooth muscle cells proliferation by increasing expression of cell-cycle regulators such as CDKN2B or CDKN1A independently of TGFB1 signaling. Ligand of integrins ITGAV:ITGB3 and ITGA5:ITGB1, acts directly upon endothelial cells to stimulate pro-angiogenic activities and induces angiogenesis. In endothelial cells, supports cell adhesion, induces directed cell migration (chemotaxis) and promotes cell survival. Also plays a role in cutaneous wound healing acting as integrin receptor ligand. Supports skin fibroblast adhesion through ITGA5:ITGB1 and ITGA6:ITGB1 and induces fibroblast chemotaxis through ITGAV:ITGB5. Seems to enhance bFGF-induced DNA synthesis in fibroblasts (By similarity). Involved in bone regeneration as a negative regulator (PubMed:23653360). Enhances the articular chondrocytic phenotype, whereas it repressed the one representing endochondral ossification (By similarity). Impairs pancreatic beta-cell function, inhibits beta-cell proliferation and insulin secretion (PubMed:23705021). Plays a role as negative regulator of endothelial pro-inflammatory activation reducing monocyte adhesion, its anti-inflammatory effects occur secondary to the inhibition of NF-kappaB signaling pathway (By similarity). Contributes to the control and coordination of inflammatory processes in atherosclerosis (PubMed:24722330). Attenuates inflammatory pain through regulation of IL1B- and TNF-induced MMP9, MMP2 and CCL2 expression. Inhibits MMP9 expression through ITGB1 engagement (By similarity).|||Interacts with FBLN1. Interacts (via CTCK domain) with NOTCH1 (via the EGF-like repeat region). Interacts with GJA1/CX43. Interacts with ITGA5:ITGB1, ITGAV:ITGB3 and ITGAV:ITGB5. Interacts with ZDHHC22; the interaction may lead to CCN3 palmitoylation (PubMed:29287726).|||May be palmitoylated on Cys-241, which is important for extracellular secretion.|||Mutants develop normally but have enhanced arterial neointimal hyperplasia in response to injury (PubMed:20139355). Animals show an accelerated bone regeneration comparing to in wild-type mice (PubMed:24722330).|||Secreted|||Up-regulated in the early phase of bone regeneration.|||gap junction http://togogenome.org/gene/10090:Actr8 ^@ http://purl.uniprot.org/uniprot/Q8R2S9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the actin family. ARP8 subfamily.|||Chromosome|||Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80. Exists as monomers and dimers, but the dimer is most probably the biologically relevant form required for stable interactions with histones that exploits the twofold symmetry of the nucleosome core (By similarity).|||Nucleus|||Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize (By similarity).|||Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Required for the recruitment of INO80 (and probably the INO80 complex) to sites of DNA damage Strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting it may act as a nucleosome recognition module within the complex (By similarity). http://togogenome.org/gene/10090:Inha ^@ http://purl.uniprot.org/uniprot/Q04997 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TGF-beta family.|||Dimeric, linked by one or more disulfide bonds. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B.|||Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. Inhibin deficient mice are viable but are acutely sensitive to development of gonadal sex-cord stromal tumors.|||Proteolytic processing yields a number of bioactive forms, consisting either solely of the mature alpha chain, of the most N-terminal propeptide linked through a disulfide bond to the mature alpha chain, or of the entire proprotein.|||Secreted http://togogenome.org/gene/10090:Tra2b ^@ http://purl.uniprot.org/uniprot/P62996 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the splicing factor SR family.|||Found in a pre-mRNA exonic splicing enhancer (ESE) complex with TRA2B/SFRS10, SNRNP70, SNRPA1 and SRRM1. Binds to A3 enhancer proteins SFRS4, SFRS5, SFRS6 and SFRS9. Interacts with CPSF6, RBMY1A1, RBMX, RNPS1 and phosphorylated SFRS13A (By similarity). Interacts with SAFB/SAFB1 (By similarity). Interacts with ILDR1 (via C-terminus) and ILDR2 (PubMed:28785060).|||Induced by reoxygenation following hypoxia and by exposure to silica. Repressed by interferon gamma, LPS and TPA.|||Nucleus|||Phosphorylated in the RS domains.|||Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing (PubMed:28785060). Can either activate or suppress exon inclusion. Acts additively with RBMX to promote exon 7 inclusion of the survival motor neuron SMN2. Activates the splicing of MAPT/Tau exon 10. Alters pre-mRNA splicing patterns by antagonizing the effects of splicing regulators, like RBMX. Binds to the AG-rich SE2 domain in the SMN exon 7 RNA. Binds to pre-mRNA (By similarity).|||Widely expressed. Highly expressed in uterus and brain. Expressed in inner ear (PubMed:28785060). http://togogenome.org/gene/10090:Klhl6 ^@ http://purl.uniprot.org/uniprot/Q6V595 ^@ Disruption Phenotype|||Function|||Induction|||Tissue Specificity ^@ Expressed in embryonic blood vessel endothelial cells but not in the vasculature of adult organs. In adults, detected at high levels in hematopoietic and lymphoid organs.|||Involved in B-lymphocyte antigen receptor signaling and germinal center formation.|||Mice show impaired antigen-dependent germinal center formation and B-cell antigen receptor (BCR) signaling. The number of mature B-cells is reduced.|||Up-regulated during germinal center formation. http://togogenome.org/gene/10090:Or4a47 ^@ http://purl.uniprot.org/uniprot/Q8VGP1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp4a32 ^@ http://purl.uniprot.org/uniprot/A2A8T1 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Psmc3 ^@ http://purl.uniprot.org/uniprot/O88685|||http://purl.uniprot.org/uniprot/Q3TKG4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC3 and few additional components. Interacts with PAAF1.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC3 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Ttn ^@ http://purl.uniprot.org/uniprot/E9Q8N1 ^@ Similarity ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. http://togogenome.org/gene/10090:Tas2r122 ^@ http://purl.uniprot.org/uniprot/D3YU55 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane http://togogenome.org/gene/10090:Or7g16 ^@ http://purl.uniprot.org/uniprot/Q8VFM8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Xdh ^@ http://purl.uniprot.org/uniprot/Q00519 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the xanthine dehydrogenase family.|||Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Binds 2 [2Fe-2S] clusters per subunit.|||By interferon.|||Can be converted from the dehydrogenase form (D) to the oxidase form (O) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups.|||Contains sulfhydryl groups that are easily oxidized (in vitro); this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O).|||Cytoplasm|||Homodimer. Interacts with BTN1A1.|||Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species.|||Peroxisome|||Secreted|||Subject to partial proteolysis; this alters the enzyme from the dehydrogenase form (D) to the oxidase form (O). http://togogenome.org/gene/10090:Or10ac1 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1M2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem151b ^@ http://purl.uniprot.org/uniprot/Q68FE7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM151 family.|||Membrane http://togogenome.org/gene/10090:Gsdmd ^@ http://purl.uniprot.org/uniprot/A0A679AXP3|||http://purl.uniprot.org/uniprot/Q9D8T2 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage at Asp-276 by CASP1 (mature and uncleaved precursor forms), CASP4/CASP11 or CASP8 relieves autoinhibition and is sufficient to initiate pyroptosis (PubMed:26375259, PubMed:26611636, PubMed:32554464, PubMed:32553275). Cleavage by CASP1 and CASP4/CASP11 is not strictly dependent on the consensus cleavage site on GSDMD but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32554464, PubMed:32553275). Cleavage by CASP8 takes place following inactivation of MAP3K7/TAK1 by Yersinia toxin YopJ (PubMed:30361383, PubMed:30381458). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis, but generates the Gasdermin-D, p13 chain, which translocates to the nucleus and acts as a transcription regulator (PubMed:37327784). Cleavage by papain allergen generates the Gasdermin-D, p40 chain (PubMed:35794369).|||Expression starts at 8.5 dpc and increases from 13.5 dpc on. Still detected after birth.|||Forms a ring-shaped pore complex containing 27-28 subunits that inserts into the membrane. The pore conduit is predominantly negatively charged, facilitating the release of mature interleukin-1 (IL1B and IL18). In contrast interleukin-1 precursors are not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation.|||Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane (PubMed:34289345). Homooligomerization is promoted by the mTORC1 complex in macrophages (PubMed:34289345). In response to a canonical inflammasome stimulus, such as nigericin, recruited to NLRP3 inflammasone with similar kinetics to that of uncleaved CASP1 precursor (PubMed:26611636). Although this recruitment is also observed in the absence of PYCARD, it is more efficient in its presence (PubMed:26611636).|||Inflammasome|||Intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of cleavage by inflammatory caspases CASP1 or CASP4/CASP11 (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:29576317, PubMed:31097341). The linker helix loop inserts into the N-terminal domain (By similarity). The intrinsic pyroptosis-inducing activity is carried by Gasdermin-D, N-terminal, that is released upon cleavage by inflammatory caspases (PubMed:26375003, PubMed:26375259, PubMed:26611636).|||Knockout mice are born at the expected Mendelian rate and do not exhibit any overt phenotype in normal housing conditions. The gastrointestinal tract develops normally. They are however resistant to LPS-induced lethal septic shock. Primary bone marrow-derived macrophages fail to undergo pyroptosis in response to canonical (acting via CASP1), as well as to non-canonical (acting via CASP4) inflammasome activators. CASP1-mediated IL1B release is also impaired, but not CASP1 autoprocessing, nor IL1B maturation.|||Membrane|||Mitochondrion membrane|||Nucleus|||Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-D, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190).|||Produced by the cleavage by papain allergen (PubMed:35794369). After cleavage, moves to the plasma membrane and homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the specific release of mature interleukin-33 (IL33), promoting type 2 inflammatory immune response (PubMed:35794369, PubMed:35749514).|||Promotes pyroptosis in response to microbial infection and danger signals (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190, PubMed:32820063, PubMed:34289345, PubMed:35705808). Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1 or CASP4/CASP11 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:27383986, PubMed:27385778, PubMed:27418190, PubMed:35705808). After cleavage, moves to the plasma membrane where it strongly binds to inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine (PubMed:27383986, PubMed:27339137). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukin-1 (IL1B and IL18) and triggering pyroptosis (PubMed:27383986, PubMed:29274245, PubMed:29195811, PubMed:33883744). Gasdermin pores also allow the release of mature caspase-7 (CASP7) (PubMed:35705808). Also forms pores in the mitochondrial membrane, resulting in release of mitochondrial DNA (mtDNA) into the cytosol (PubMed:37001519). Gasdermin-D, N-terminal released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity (PubMed:27383986). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (PubMed:27383986). Also active in response to MAP3K7/TAK1 inactivation by Yersinia toxin YopJ, which triggers cleavage by CASP8 and subsequent activation (PubMed:30361383, PubMed:30381458). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27383986).|||Secreted|||Succination of Cys-192 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits processing by caspases, and ability to initiate pyroptosis (PubMed:32820063). Succination modification is catalyzed by a non-enzymatic reaction caused by an accumulation of fumarate (PubMed:32820063).|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:29576317, PubMed:31097341). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-D, N-terminal) following cleavage by inflammatory caspases CASP1, CASP4/CASP11 or CASP8 (PubMed:26375003, PubMed:26375259, PubMed:26611636, PubMed:30361383, PubMed:30381458, PubMed:32554464, PubMed:32553275). Cleavage at Asp-88 by CASP3 or CAPS7 inactivates the ability to mediate pyroptosis (By similarity).|||Transcription coactivator produced by the cleavage by CASP3 or CASP7 in the upper small intestine in response to dietary antigens (PubMed:37327784). Required to maintain food tolerance in small intestine: translocates to the nucleus and acts as a coactivator for STAT1 to induce the transcription of CIITA and MHC class II molecules, which in turn induce type 1 regulatory T (Tr1) cells in upper small intestine (PubMed:37327784).|||cytosol http://togogenome.org/gene/10090:Dcbld1 ^@ http://purl.uniprot.org/uniprot/Q9D4J3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Or14c45 ^@ http://purl.uniprot.org/uniprot/Q7TS07 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Med16 ^@ http://purl.uniprot.org/uniprot/E9QP84|||http://purl.uniprot.org/uniprot/G3UW74|||http://purl.uniprot.org/uniprot/Q3UET8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 16 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.|||Nucleus http://togogenome.org/gene/10090:Pebp1 ^@ http://purl.uniprot.org/uniprot/P70296|||http://purl.uniprot.org/uniprot/Q5EBQ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phosphatidylethanolamine-binding protein family.|||Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase. Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation (By similarity).|||Cytoplasm|||HCNP is expressed in brain. Increased expression in aged senescence-accelerated mice.|||HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity).|||Has a tendency to form dimers by disulfide cross-linking. Interacts with RAF1 and this interaction is enhanced if RAF1 is phosphorylated on residues 'Ser-338', 'Ser-339', 'Tyr-340' and 'Tyr-341'. Interacts with ALOX15; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade (By similarity). http://togogenome.org/gene/10090:Actrt3 ^@ http://purl.uniprot.org/uniprot/Q8BXF8 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the actin family.|||Cytoplasm|||Interacts with PFN3.|||Nucleus|||Testis specific (at protein level). Expressed specifically in haploid germ cells.|||cytoskeleton http://togogenome.org/gene/10090:Prps1 ^@ http://purl.uniprot.org/uniprot/Q9D7G0 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subunit ^@ Activated by magnesium and inorganic phosphate.|||Belongs to the ribose-phosphate pyrophosphokinase family.|||Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.|||Expressed in both vestibular and cochlea hair cells in early developing and postnatal mice and can also be detected in the spiral ganglion cells in at post natal day 6.|||Homodimer. The active form is probably a hexamer composed of 3 homodimers (By similarity). http://togogenome.org/gene/10090:H2bc13 ^@ http://purl.uniprot.org/uniprot/P10853 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Egfl7 ^@ http://purl.uniprot.org/uniprot/Q3UTJ7|||http://purl.uniprot.org/uniprot/Q9QXT5 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed early during mouse embryogenesis in the yolk sac mesoderm and in the developing vascular system. At 7.5 dpc, it is expressed in the primitive blood islands where the first endothelial cells differentiate. At 10.5 and 13.5 dpc expression is restricted to endothelial cells.|||Expressed specifically by endothelial cells of the highly vascularized organs heart, lung and kidney.|||Interacts with ITGAV/ITGB3 in an RGD-dependent manner, increasing endothelial cell's motility.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Regulates vascular tubulogenesis in vivo. Inhibits platelet-derived growth factor (PDGF)-BB-induced smooth muscle cell migration and promotes endothelial cell adhesion to the extracellular matrix and angiogenesis.|||extracellular space http://togogenome.org/gene/10090:Stxbp1 ^@ http://purl.uniprot.org/uniprot/O08599 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Expressed in the inner and outer plexiform layers of the retina (at protein level).|||Interacts with SYTL4 (By similarity). Interacts with STX1A; the interaction recruits SNARE complex components SNAP25 and VAMP2 and mediates neurotransmitter release from neurons (PubMed:21445306, PubMed:28821673). Interacts with alpha-synuclein/SNCA; this interaction controls SNCA self-replicating aggregation (By similarity). Interacts with RAB3A; this interaction promotes RAB3A dissociation from the vesicle membrane (By similarity). Interacts with CABP5 (By similarity). Interacts with APBA1 (PubMed:21445306).|||Membrane|||Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins (By similarity). Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. Involved in the release of neurotransmitters from neurons through interacting with SNARE complex component STX1A and mediating the assembly of the SNARE complex at synaptic membranes (PubMed:21445306, PubMed:28821673). May play a role in determining the specificity of intracellular fusion reactions (By similarity).|||cytosol http://togogenome.org/gene/10090:Ager ^@ http://purl.uniprot.org/uniprot/Q62151 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cell surface pattern recognition receptor that senses endogenous stress signals with a broad ligand repertoire including advanced glycation end products, S100 proteins, high-mobility group box 1 protein/HMGB1, amyloid beta/APP oligomers, nucleic acids, phospholipids and glycosaminoglycans (PubMed:21270403, PubMed:32670276). Advanced glycosylation end products are nonenzymatically glycosylated proteins which accumulate in vascular tissue in aging and at an accelerated rate in diabetes. These ligands accumulate at inflammatory sites during the pathogenesis of various diseases, including diabetes, vascular complications, neurodegenerative disorders, and cancers and RAGE transduces their binding into pro-inflammatory responses. Upon ligand binding, uses TIRAP and MYD88 as adapters to transduce the signal ultimately leading to the induction or inflammatory cytokines IL6, IL8 and TNFalpha through activation of NF-kappa-B. Interaction with S100A12 on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key pro-inflammatory mediators (By similarity). Interaction with S100B after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Contributes to the translocation of amyloid-beta peptide (ABPP) across the cell membrane from the extracellular to the intracellular space in cortical neurons (PubMed:19901339). ABPP-initiated RAGE signaling, especially stimulation of p38 mitogen-activated protein kinase (MAPK), has the capacity to drive a transport system delivering ABPP as a complex with RAGE to the intraneuronal space. Participates in endothelial albumin transcytosis together with HMGB1 through the RAGE/SRC/Caveolin-1 pathway, leading to endothelial hyperpermeability (By similarity). Mediates the loading of HMGB1 in extracellular vesicles (EVs) that shuttle HMGB1 to hepatocytes by transferrin-mediated endocytosis and subsequently promote hepatocyte pyroptosis by activating the NLRP3 inflammasome (By similarity). Promotes also extracellular hypomethylated DNA (CpG DNA) uptake by cells via the endosomal route to activate inflammatory responses (By similarity).|||Constitutive homodimer; disulfide-linked. Forms homooligomers (By similarity). Interacts with S100A1 and APP (PubMed:19901339). Interacts with S100B, S100A12 and S100A14 (PubMed:10399917). Interacts with TIRAP (By similarity). Interacts with HMGB1 (By similarity).|||Down-regulates receptor for advanced glycosylation end products (RAGE)-ligand induced signaling through various MAPK pathways including ERK1/2, p38 and SAPK/JNK. Significantly affects tumor cell properties through decreasing cell migration, invasion, adhesion and proliferation, and increasing cellular apoptosis. Exhibits drastic inhibition on tumorigenesis in vitro.|||In deletion mutant mice, the elevation of serum TNF-alpha, IL6 and EDN1 and the tissue damage induced by LPS is significantly attenuated when compared with WT mice (PubMed:21270403). The lower hepatic expression of pro-inflammatory cytokines, while the activation of immune cells remains unaffected, results in improved survival after challenge with D-galactosamine (PubMed:32670276).|||Is able to advanced glycosylation end product (AGE)-induce nuclear factor NF-kappa-B activation.|||Isoform 1: Expressed at higher levels in the coronary arterioles in type 2 diabetic mice (at protein level). Endothelial cells (PubMed:18539754). Expressed in lung, kidney, brain and heart. Most prevalent isoform with the highest level in heart (PubMed:19164451). Isoform 2: Expressed in brain, lung, kidney and small intestine with the highest level in lung. Expressed in brain, lung, kidney and small intestine with the highest level in small intestine (at protein level). Detected in neurons of the cerebrum, bronchial epithelium, endothelial cells, tubular cells of kidney and epithelial cells of small intestine (at protein level). Expression is increased in the kidney of diabetic wild-type mice (at protein level), but not in the other tissues (PubMed:16503878). Expressed only in kidney. Expression is increased in the kidney of diabetic mice (PubMed:19164451). Isoform 3: Expressed in lung, kidney and heart. The second most prevalent isoform with the highest level in lung. Not expressed in brain (PubMed:19164451). Isoform 4: Expressed at very low level in lung only (PubMed:19164451). Isoform 5: Expressed at very low level in lung only (PubMed:19164451). Isoform 6: Expressed at very low level in lung only (PubMed:19164451). Isoform 7: Expressed at very low level in heart only (PubMed:19164451). Isoform 8: Expressed at very low level in lung only (PubMed:19164451). Isoform 9: Expressed at very low level in heart only (PubMed:19164451). Isoform 10: Expressed in lung, brain, heart and kidney with a very high level in kidney (PubMed:24260107). Isoform 11: Expressed in brain, kidney and heart. Not expressed in lung (PubMed:19164451). Isoform 12: Expressed at very low level in lung and kidney (PubMed:19164451). Isoform 13: Expressed at very low level in lung only (PubMed:19164451).|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane|||Phosphorylated on its cytoplasmic domain by PKCzeta/PRKCZ upon ligand binding.|||Secreted|||Targeted by the ubiquitin E3 ligase subunit FBXO10 to mediate its ubiquitination and degradation. http://togogenome.org/gene/10090:Armcx2 ^@ http://purl.uniprot.org/uniprot/Q6A058|||http://purl.uniprot.org/uniprot/Q8BJ81|||http://purl.uniprot.org/uniprot/Q8BTE8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the eutherian X-chromosome-specific Armcx family.|||May regulate the dynamics and distribution of mitochondria in neural cells.|||Membrane|||Mitochondrion|||Mitochondrion outer membrane|||Widely expressed in the adult nervous tissue, especially in the forebrain, including the cerebral cortex, hippocampus and thalamus. http://togogenome.org/gene/10090:Wdr20rt ^@ http://purl.uniprot.org/uniprot/Q9D5R2 ^@ Function|||Subunit ^@ Interacts with USP12. Component of the USP12/WDR20/WDR48 deubiquitinating complex. Interacts with USP46.|||Regulator of deubiquitinating complexes. Activates deubiquitinating activity of complexes containing USP12. http://togogenome.org/gene/10090:Fam20c ^@ http://purl.uniprot.org/uniprot/Q5MJS3 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the FAM20 family.|||Endoplasmic reticulum|||Golgi apparatus membrane|||Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth (PubMed:22900076, PubMed:22732358, PubMed:25789606). Constitutes the main protein kinase for extracellular proteins, generating the majority of the extracellular phosphoproteome (By similarity). Mainly phosphorylates proteins within the Ser-x-Glu/pSer motif, but also displays a broader substrate specificity (By similarity). Phosphorylates ERO1A, enhancing its activity which is required to maintain endoplasmic reticulum redox homeostasis and for oxidative protein folding (By similarity). During endoplasmic reticulum stress, phosphorylates P4HB/PDIA1 which induces a functional switch, causing P4HB to change from an oxidoreductase to a molecular chaperone (By similarity). This is critical to maintain ER proteostasis and reduce cell death under ER stress (By similarity). Phosphorylation of P4HB also promotes its interaction with ERN1, leading to reduced activity of ERN1, a key sensor for the endoplasmic reticulum unfolded protein response (By similarity). Required for osteoblast differentiation and mineralization (By similarity). Phosphorylates casein as well as a number of proteins involved in biomineralization such as AMELX, AMTN, ENAM and SPP1 (PubMed:25789606). In addition to its role in biomineralization, also plays a role in lipid homeostasis, wound healing and cell migration and adhesion (By similarity).|||Homodimer; disulfide-linked (By similarity). Interacts with FAM20A; probably forming a heterotetramer of 2 subunits of FAM20A and 2 subunits of FAM20C (PubMed:25789606). Interacts with COPII components SEC23A and SEC24A; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles (By similarity).|||In the developing tooth, initial expression observed in odontoblasts at all stages of development. At later stages, restricted expression pattern in ameloblasts. Also observed in osteoblasts in the alveolar bone.|||In the mammary gland, expressed at higher levels in lactating mice than in virgin mice (at protein level) (PubMed:29858230). Highly expressed in the tooth. No expression in the dental pulp. At the secretory stage of amelogenesis, it is detected in the matrix of the enamel, in the ameloblasts, and within the cells adjoining the stratum intermedium (a tissue layer analogous to the stellate reticulum seen in the developing molar). Strong expression is observed in maturation stage ameloblasts and throughout the non-cornified layers of the gingival epithelium. Expressed at moderate levels in bone and at low levels in kidney, liver, brain and lung. Very low expression, if any, in spleen and skeletal muscle.|||Mice survive to adulthood and show biomineralization defects, suc as severe amelogenesis imperfecta (AI). In addition, mice are severely hypophosphatemic and develop notable lesions in both dentin and bone.|||N-glycosylation is required for folding.|||Propeptide cleavage by MBTPS1/S1P promotes FAM20C secretion and maximal kinase activity which is essential for efficient osteoblast differentiation and biomineralization.|||Secreted|||Serine/threonine protein kinase activity is increased upon interaction with FAM20A. http://togogenome.org/gene/10090:Sfswap ^@ http://purl.uniprot.org/uniprot/Q3USH5 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Plays a role as an alternative splicing regulator. Regulates its own expression at the level of RNA processing. Also regulates the splicing of fibronectin and CD45 genes. May act, at least in part, by interaction with other R/S-containing splicing factors. Represses the splicing of MAPT/Tau exon 10 (By similarity). http://togogenome.org/gene/10090:Gzma ^@ http://purl.uniprot.org/uniprot/P11032 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent pyroptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA.|||Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytoplasmic granule|||Found in cytotoxic lymphocytes and in normal lymphoid tissues such as thymus and spleen.|||Homodimer; disulfide-linked. Interacts with APEX1.|||More abundant in lymphoid tissues than isoform HF2.|||Secreted|||The predicted cleavage site for the activation peptide of HF2 is uncertain. It could have either 2 (ER) or 7 (KRGGCER) AA. http://togogenome.org/gene/10090:Slc1a4 ^@ http://purl.uniprot.org/uniprot/O35874|||http://purl.uniprot.org/uniprot/Q3US35|||http://purl.uniprot.org/uniprot/Q3UTP8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.|||Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A4 subfamily.|||Melanosome|||Membrane|||Sodium-dependent neutral amino-acid transporter that mediates transport of alanine, serine, cysteine, proline, hydroxyproline and threonine. http://togogenome.org/gene/10090:Or10a3n ^@ http://purl.uniprot.org/uniprot/Q7TRU3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lingo4 ^@ http://purl.uniprot.org/uniprot/Q149C3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Drd4 ^@ http://purl.uniprot.org/uniprot/P51436 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Detected in olfactory bulb, hypothalamus, olfactory tubercle, brainstem and striatum.|||Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs. Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (By similarity). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (PubMed:24048828).|||Forms homo- and heterooligomers with DRD2. D4.7 allele exhibits higher affinity for homodimers compared to DRD2 heterodimers, while alleles D42. and 4.4 have similar affinities for both. The interaction with DRD2 may modulate agonist-induced downstream signaling (By similarity). Interacts with CLIC6 (By similarity). Interacts with GPRASP1. May interact with ADORA2A. Interacts with KLHL12 (By similarity).|||In contrast to human protein, does not interact with KLHL12 and is not ubiquitinated by the BCR(KLHL12) complex.|||Mice show a significant reduction in daytime contrast sensitivity.|||Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane. http://togogenome.org/gene/10090:Ush1c ^@ http://purl.uniprot.org/uniprot/Q9ES64 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (PubMed:19447093). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018).|||Detected in stereocilia of cochlear hair cells (at protein level). Isoform 1 is expressed in the eye, cochlea, vestibule, heart, kidney, small intestine and testis; it is barely visible in skeletal muscle, liver, and lung and is absent from the brain. Isoforms 2 and 3 are expressed in the cochlea and vestibule.|||Mice lacking Ush1c display abnormal brush border morphology along the length of the intestinal tract.|||Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5 (By similarity). Part of a complex composed of USH1C, USH1G and MYO7A (By similarity). Interacts with F-actin (PubMed:19447093). Interacts with USH2A (PubMed:16301217). Interacts with SLC4A7 (PubMed:16301216). Interacts (via PDZ1 domain) with the C-terminus of USHBP1 (By similarity). Interacts (via N-terminus and PDZ 2 domain) with CDH23 (PubMed:19447093). Interacts with USH1G (By similarity). Interacts with MYO7B (PubMed:26812017). Interacts with CDHR2 and CDHR5; may mediate their interaction with MYO7B at the microvilli tip (By similarity) (PubMed:26812017). Interacts (via PDZ 1 domain) with ANKS4B (PubMed:12588794, PubMed:15461667). Interacts (via PDZ 1 domain) with DOCK4 (By similarity).|||The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity.|||The PDZ 1 domain mediates interaction with ANKS4B, USHBP1, USH1G, SLC4A7.|||cytoskeleton|||cytosol|||microvillus http://togogenome.org/gene/10090:Elovl4 ^@ http://purl.uniprot.org/uniprot/Q9EQC4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ELO family. ELOVL4 subfamily.|||Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that catalyzes the synthesis of very long chain saturated (VLC-SFA) and polyunsaturated (PUFA) fatty acids that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May play a critical role in early brain and skin development.|||Endoplasmic reticulum membrane|||Expressed in the ocular tissues of the retina at 10.5 dpc and becomes restricted predominantly to the photoreceptor layer in the mature retina (at protein level). Expressed in the embryo at 7 dpc.|||Expressed in the retina, exclusively in photoreceptor cells and in the brain, skin, testis and lens.|||N-glycosylated.|||Oligomer.|||Rod or cone-specific conditional knockout of Elovl4 results in a decrease in very long chain (C30-C34) polyunsaturated fatty acids in the retina, but has no effect on photoreceptors survival, phototransduction, synaptic transmission or visual behavior.|||The C-terminal di-lysine motif confers endoplasmic reticulum localization. http://togogenome.org/gene/10090:Dpysl4 ^@ http://purl.uniprot.org/uniprot/Q3TMU8 ^@ Similarity ^@ Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family. http://togogenome.org/gene/10090:Mettl8 ^@ http://purl.uniprot.org/uniprot/A2AUU0 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Absent in embryonic lung but is induced in a fibroblast cell line by stretch.|||Absent in undifferentiated embryonic lung mesenchymal cells, but expression is induced by stretch.|||According to some authors, contains a SANT domain but this domain is not detected by any prediction tool.|||Belongs to the methyltransferase superfamily. METL family.|||Cytoplasm|||Expressed in mature adipose tissue.|||Expressed in undifferentiated progenitor cells, while its expression is inhibited by stretch.|||Induced in stretched embryonic lung mesenchymal cells.|||Interacts with EP300.|||Mice were born with normal Mendelian ratio without developmental defects (PubMed:28655767). Cells show reduced N(3)-methylcytidine modification in mRNAs (PubMed:28655767).|||Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of mitochondrial tRNA(Ser)(UCN) and tRNA(Thr) (By similarity). N(3)-methylcytidine methylation modification regulates mitochondrial translation efficiency and is required for activity of the respiratory chain (By similarity). N(3)-methylcytidine methylation of mitochondrial tRNA(Ser)(UCN) requires the formation of N(6)-dimethylallyladenosine(37) (i6A37) by TRIT1 as prerequisite (By similarity). May also mediate N(3)-methylcytidine modification of mRNAs (PubMed:28655767). The existence of N(3)-methylcytidine modification on mRNAs is however unclear, and additional evidences are required to confirm the role of the N(3)-methylcytidine-specific mRNA methyltransferase activity of METTL8 in vivo (By similarity).|||Mitochondrion|||Nucleus|||Overexpression in lung progenitor cells stimulates smooth muscle-specific gene expression and suppresses adipogenic gene expression.|||Sequence differs from the displayed sequence in the N-terminal region.|||Stimulates adipogenesis. http://togogenome.org/gene/10090:Snapc5 ^@ http://purl.uniprot.org/uniprot/Q8R2K7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC5 interacts with SNAPC4 (By similarity).|||Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box (By similarity). http://togogenome.org/gene/10090:Hspbap1 ^@ http://purl.uniprot.org/uniprot/Q8BK58 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with CRYAB and HSPB1.|||May play a role in cellular stress response. http://togogenome.org/gene/10090:Cdc42se1 ^@ http://purl.uniprot.org/uniprot/Q8BHL7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CDC42SE/SPEC family.|||Cell membrane|||Interacts with CDC42 (in GTP-bound form). Interacts weakly with RAC1 and not at all with RHOA (By similarity).|||Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages (By similarity).|||The CRIB domain mediates interaction with CDC42.|||cytoskeleton http://togogenome.org/gene/10090:Setd1a ^@ http://purl.uniprot.org/uniprot/E9PYH6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Chromosome|||Component of the SET1A complex composed of the catalytic subunit SETD1A, WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 homotrimer (By similarity). Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity (By similarity). Interacts with BOD1L1 (via COMPASS-Shg1 domain) at replication forks (By similarity). Interacts with HCFC1. Interacts with ASH2/ASH2L, CXXC1/CFP1 and RBBP5. Interacts (via the RRM domain) with WDR82. Interacts (via the RRM domain) with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) only in the presence of WDR82. Binds specifically to CTD heptad repeats phosphorylated on 'Ser-5' of each heptad. Interacts with ZNF335. Interacts with SUPT6H (By similarity). Interacts with NAP1L1 (PubMed:29490266). Interacts (via WIN motif) with WDR5 (By similarity).|||High expression is detected in the oocyte that declines to a stable level from the 8-cell stage until 8.5 dpc.|||Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place (By similarity). Responsible for H3K4me3 enriched promoters and transcriptional programming of inner mass stem cells and neuron progenitors during embryogenesis (PubMed:24550110, PubMed:29490266, PubMed:31197650). Required for H3K4me1 mark at stalled replication forks. Mediates FANCD2-dependent nucleosome remodeling and RAD51 nucleofilaments stabilization at reversed forks, protecting them from nucleolytic degradation. Does not methylate 'Lys-4' of histone H3 if the neighboring 'Lys-9' residue is already methylated (By similarity).|||Mutant embryos fail to gastrulate and die before or at 7.5 dpc.|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Gna14 ^@ http://purl.uniprot.org/uniprot/P30677|||http://purl.uniprot.org/uniprot/Q8C3M7|||http://purl.uniprot.org/uniprot/Q8CBT5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the G-alpha family. G(q) subfamily.|||G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.|||Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. http://togogenome.org/gene/10090:Defa25 ^@ http://purl.uniprot.org/uniprot/Q5G864 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Phyhipl ^@ http://purl.uniprot.org/uniprot/F7D3N3|||http://purl.uniprot.org/uniprot/Q8BGT8 ^@ Function|||Sequence Caution|||Similarity ^@ Belongs to the PHYHIP family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||May play a role in the development of the central system. http://togogenome.org/gene/10090:Cdca7 ^@ http://purl.uniprot.org/uniprot/Q9D0M2 ^@ Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with MYC (via C-terminus), YWHAE and YWHAZ.|||Nucleus|||Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. May play a role as transcriptional regulator (By similarity).|||Phosphorylation at Thr-170 promotes interaction with YWHAE and YWHAZ, dissociation from MYC and sequestration in the cytoplasm.|||Transgenic mice overexpress Cdca7 in both T- and B-cell compartments. At 1 year of age, they exhibit elevated incidence of lymphomas, significant increased frequency of solid tumors and a 2-fold increased risk of lymphoid malignancies compared to their littermates. http://togogenome.org/gene/10090:Xlr ^@ http://purl.uniprot.org/uniprot/P05531|||http://purl.uniprot.org/uniprot/Q544L6|||http://purl.uniprot.org/uniprot/Q8BS74 ^@ Similarity|||Tissue Specificity ^@ Belongs to the XLR/SYCP3 family.|||Expressed in lymphoid cells. http://togogenome.org/gene/10090:Inf2 ^@ http://purl.uniprot.org/uniprot/Q0GNC1 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the formin homology family.|||Interacts with profilin and actin at the FH1 and FH2 domains respectively. Interacts with DAAM2 (By similarity).|||Phosphate inhibits both the depolymerization and severing activities.|||Regulated by autoinhibition due to intramolecular GBD-DAD binding.|||Severs actin filaments and accelerates their polymerization and depolymerization.|||The WH2 domain acts as the DAD (diaphanous autoregulatory) domain and binds to actin monomers.|||The severing activity is dependent on covalent attachment of the FH2 domain to the C-terminus.|||perinuclear region http://togogenome.org/gene/10090:Pccb ^@ http://purl.uniprot.org/uniprot/Q99MN9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AccD/PCCB family.|||Broadly expressed. Most abundantly expressed in the kidney, liver, small intestine and stomach.|||Mitochondrion matrix|||The beta subunit contains the carboxyl transferase (CT) domain.|||The holoenzyme is a dodecamer composed of 6 PCCA/alpha subunits and 6 PCCB/beta subunits.|||This is one of the 2 subunits of the biotin-dependent propionyl-CoA carboxylase (PCC), a mitochondrial enzyme involved in the catabolism of odd chain fatty acids, branched-chain amino acids isoleucine, threonine, methionine, and valine and other metabolites. Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-CoA/(S)-methylmalonyl-CoA (By similarity). Within the holoenzyme, the alpha subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, while the beta subunit then transfers the carboxyl group from carboxylated biotin to propionyl-CoA (By similarity). Propionyl-CoA carboxylase also significantly acts on butyryl-CoA/butanoyl-CoA, which is converted to ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA (By similarity). Other alternative minor substrates include (2E)-butenoyl-CoA/crotonoyl-CoA (By similarity). http://togogenome.org/gene/10090:Zfp128 ^@ http://purl.uniprot.org/uniprot/Q8BGV5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Interacts with SMAD1 (via MH1 and MH2 domains). Interacts with SMAD5. Interacts weakly with SMAD2, SMAD3 and SMAD4.|||Nucleus|||Strongly expressed in testis, where it localizes to seminiferous tubules. Weakly expressed in heart, brain, lung, liver and kidney.|||Transcriptional repressor. May modulate BMP and TGF-beta signal transduction, through its interaction with SMAD proteins.|||Ubiquitously expressed in embryos. Detected from stage 7 dpc onwards, reaching peak levels at stage 11 dpc and declining by stages 15 dpc and 17 dpc. http://togogenome.org/gene/10090:Bloc1s4 ^@ http://purl.uniprot.org/uniprot/Q8VED2 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BLOC1S4 family.|||Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking.|||Cytoplasm|||Defects in Cno are the cause of the cappuccino (Cno) mutant, which is characterized by a severe oculocutaneous albinism due to abnormal melanosome formation, and prolonged bleeding due to deficiency of platelet dense body contents.|||Octamer composed of one copy each BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8 (By similarity). Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. Interacts with BLOC1S5 and BLOC1S6.|||Widely expressed. http://togogenome.org/gene/10090:Mrpl4 ^@ http://purl.uniprot.org/uniprot/Q9DCU6 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL4 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins. Interacts with MIEF1 upstream open reading frame protein.|||Mitochondrion http://togogenome.org/gene/10090:Crb2 ^@ http://purl.uniprot.org/uniprot/Q80YA8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Apical polarity protein that plays a central role during the epithelial-to-mesenchymal transition (EMT) at gastrulation, when newly specified mesodermal cells move inside the embryo (PubMed:26496195, PubMed:27870829). Acts by promoting cell ingression, the process by which cells leave the epithelial epiblast and move inside the embryo to form a new tissue layer (PubMed:27870829). The anisotropic distribution of CRB2 and MYH10/myosin-IIB at cell edges define which cells will ingress: cells with high apical CRB2 are probably extruded from the epiblast by neighboring cells with high levels of apical MYH10/myosin-IIB (PubMed:27870829). Also required for maintenance of the apical polarity complex during development of the cortex.|||Belongs to the Crumbs protein family.|||Embryonic lethality due impaired gastrulation (PubMed:22072575, PubMed:27870829). Mesoderm formation is disrupted, and cells do not ingress (PubMed:27870829). Instead, a single layer forms, and the embryo fails to properly establish its body plan, leading to embryonic arrest (PubMed:27870829). Conditional deletion in the developing retina leads to progressive disorganization during late retinal development: retina show progressive thinning of the photoreceptor layer and sites of cellular mislocalization (PubMed:23001562). Conditional deletion in the dorsal telencephalon leads to defects in the maintenance of the apical complex (PubMed:26802325).|||Expressed in early embryonic cells, more specifically in embryonic regions undergoing dramatic rearrangement, such as the developing neuroepithelium which proceeds with neural tube closure, the anterior splitting lateral plate mesoderm that wraps the pericardial cavity and the differentiating somite epithelium (PubMed:22072575). Widely expressed throughout the epiblast and the lateral plate mesoderm at 7 dpc. At 7.5 dpc-7.75 dpc, continues to be expressed in these regions, and expression is also found on the apical side of the embryonic endoderm, and extraembryonic amnion and allantois (PubMed:22072575). At 8-8.5 dpc, expression is also detected in the heart tube, foregut and the apical side of the somite epithelium (PubMed:22072575). Stronger expression is detected on the apical sides of the splitting lateral plate mesoderm, and the apical side of the neural ectoderm at trunk region (PubMed:22072575). Not expressed in the notochord plate or the extra-embryonic endoderm (PubMed:22072575). Expressed in the developing spinal cord, eye, and forebrain at 10.5 dpc (PubMed:17920587). Expressed in the ventricular layers of the developing neural tube along the entire cranial-caudal length, including the anterior forebrain and the posterior spinal cord at 11.5 dpc (PubMed:17920587). Expressed in apical epithelial kidney cells at 15.5 dpc (PubMed:17920587).|||In the adult eye, strongly expressed in the outer nuclear layer, containing the cell bodies of the photoreceptor cells, and in the inner nuclear layer, containing the cell bodies of the horizontal, bipolar, amacrine, and Mueller glial cells (PubMed:15851977). Also expressed in some cells in the ganglion cell layer (or may be displaced amacrine cells rather than ganglion cells) (PubMed:15851977).|||Interacts (via intracellular domain) with EPB41L5.|||O-glucosylated by POGLUT1 at Ser-271; consists of an O-glucose trisaccharide, in which the O-glucose is elongated by the addition of two xylose residues (PubMed:26496195). O-glucosylation is required for localization at the plasma membrane (PubMed:26496195). http://togogenome.org/gene/10090:Trim34a ^@ http://purl.uniprot.org/uniprot/Q99PP6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||Functions as antiviral protein and contributes to the defense against retroviral infections (By similarity). Acts as a capsid-specific restriction factor with the help of TRIM5 and prevents infection from non-host-adapted retroviruses. During influenza A virus infection, promotes programmed cell death by targeting ZBP1 for 'Lys-63'-linked polyubiquitination. In turn, promotes ZBP1 recruitment of RIPK3 to mediate virus-induced programmed necrosis (By similarity). Negatively regulates the function of mitochondria by enhancing mitochondrial depolarization leading to cytochrome c release and mitochondria-dependent apoptosis. Promotes also the formation of multinucleated giant cells by means of cell fusion and phagocytosis in epithelial cells (By similarity). Plays an essential role in sustaining the integrity of the inner mucus layer in the colon by controlling the exocytosis of the major component of colonic mucus MUC2 from colonic goblet cells (PubMed:32094504).|||Homotrimer. Interacts (via B-box and SPRY domain) with TRIM5.|||Mitochondrion|||Trim34a- and TRIM34b-deficient mice show an impaired integrity of the inner mucus layer. http://togogenome.org/gene/10090:Ltv1 ^@ http://purl.uniprot.org/uniprot/Q6NSQ7 ^@ Similarity ^@ Belongs to the LTV1 family. http://togogenome.org/gene/10090:Krt77 ^@ http://purl.uniprot.org/uniprot/Q08EK5|||http://purl.uniprot.org/uniprot/Q6IFZ6 ^@ Miscellaneous|||PTM|||Similarity|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Expressed in stratified epithelia.|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).|||Undergoes deimination of some arginine residues (citrullination). http://togogenome.org/gene/10090:Scn2b ^@ http://purl.uniprot.org/uniprot/Q56A07 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sodium channel auxiliary subunit SCN2B (TC 8.A.17) family.|||Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).|||Membrane|||The voltage-sensitive sodium channel consists of an ion-conducting pore-forming alpha subunit (such as SCN2A or SCN8A) regulated by one or more beta subunits (SCN1B, SCN2B, SCN3B and SCN4B). SCN1B and SCN3B are non-covalently associated with the alpha subunit. SCN2B and SCN4B are disulfide-linked to the alpha subunit (By similarity). http://togogenome.org/gene/10090:Bag6 ^@ http://purl.uniprot.org/uniprot/G3UZT6|||http://purl.uniprot.org/uniprot/Q3UF95|||http://purl.uniprot.org/uniprot/Q9Z1R2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins (PubMed:18056262, PubMed:18678708, PubMed:20713601). Functions as part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, which maintains these client proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20713601). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated by RNF126, an E3 ubiquitin-protein ligase associated with BAG6 and are sorted to the proteasome. SGTA which prevents the recruitment of RNF126 to BAG6 may negatively regulate the ubiquitination and the proteasomal degradation of client proteins. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (By similarity). BAG6 is also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. In this context, it may participate in the production of antigenic peptides and play a role in antigen presentation in immune response (PubMed:20713601). BAG6 is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. BAG6 may ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress (By similarity). By inhibiting the polyubiquitination and subsequent proteasomal degradation of HSPA2 it may also play a role in the assembly of the synaptonemal complex during spermatogenesis (PubMed:18678708). Also positively regulates apoptosis by interacting with and stabilizing the proapoptotic factor AIFM1 (PubMed:18056262). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (By similarity).|||Component of the BAG6/BAT3 complex, also named BAT3 complex, at least composed of BAG6, UBL4A and GET4/TRC35. Interacts with GET4; the interaction is direct and localizes BAG6 in the cytosol (By similarity). Interacts with UBL4A; the interaction is direct and required for UBL4A protein stability (By similarity). Interacts with AIFM1 (PubMed:18056262). Interacts with HSPA2 (PubMed:18678708). Interacts with CTCFL. Interacts with p300/EP300. Interacts (via ubiquitin-like domain) with RNF126; required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol. Interacts (via ubiquitin-like domain) with SGTA; SGTA competes with RNF126 by binding the same region of BAG6, thereby promoting deubiquitination of BAG6-target proteins and rescuing them from degradation. Interacts with ricin A chain. Interacts with VCP and AMFR; both form the VCP/p97-AMFR/gp78 complex. Interacts with SYVN1. Interacts with USP13; the interaction is direct and may mediate UBL4A deubiquitination (By similarity). Interacts with ZFAND2B (PubMed:24160817, PubMed:26337389, PubMed:26876100). Interacts with KPNA2 (By similarity). Interacts with UBQLN4 (By similarity).|||Involved in DNA damage-induced apoptosis: following DNA damage, accumulates in the nucleus and forms a complex with p300/EP300, enhancing p300/EP300-mediated p53/TP53 acetylation leading to increase p53/TP53 transcriptional activity. When nuclear, may also act as a component of some chromatin regulator complex that regulates histone 3 'Lys-4' dimethylation (H3K4me2).|||Lethality associated with pronounced developmental defects in the lung, kidney and brain. Lethality is either embryonic consecutive to abnormal brain development or perinatal associated with pronounced developmental defects in the lung and kidney. These developmental defects were associated with widespread aberrant apoptosis and proliferation. Lethality can be partially rescued in an ICR genetic background: mice are slightly smaller in size than their wild-type counterparts and show impaired genotoxic stress responses.|||May mediate ricin-induced apoptosis.|||Nucleus|||Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC).|||Ricin can induce a cleavage by the caspase CASP3. The released C-terminal peptide induces apoptosis.|||The ubiquitin-like domain mediates interaction with the E3 ubiquitin-protein ligase RNF126 which is responsible for the BAG6-dependent ubiquitination of client proteins. SGTA also binds this domain and competes with RNF126 to antagonize client protein ubiquitination and degradation. The ubiquitin-like domain also mediates the interaction with USP13.|||cytosol|||extracellular exosome http://togogenome.org/gene/10090:Rnaseh2b ^@ http://purl.uniprot.org/uniprot/Q80ZV0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNase H2 subunit B family.|||Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.|||Nucleus|||The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C. http://togogenome.org/gene/10090:Atp4a ^@ http://purl.uniprot.org/uniprot/Q64436|||http://purl.uniprot.org/uniprot/Q91WH7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.|||Cell membrane|||Expressed in parietal cells (at protein level).|||Membrane|||Mutant mice are born at the expected Mendelian rate. They develop achlorhydria, hypergastrinemia and ciliated metaplasia. The parietal cell viability or chief cell differentiation are normal when compared to wild-type littermates. Mutant parietal cells have abnormal morphology characterized by dilated canaliculi with few microvilli, spherical vesicles rather than normal tubulovesicles and enlarged mitochondria filled with concentric cristae.|||The catalytic subunit of the gastric H(+)/K(+) ATPase pump which transports H(+) ions in exchange for K(+) ions across the apical membrane of parietal cells (PubMed:7762614). Uses ATP as an energy source to pump H(+) ions to the gastric lumen while transporting K(+) ion from the lumen into the cell (PubMed:7762614). Remarkably generates a million-fold proton gradient across the gastric parietal cell membrane, acidifying the gastric juice down to pH 1 (PubMed:10764766). Within a transport cycle, the transfer of a H(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing (E1) to outward-facing state (E2). The release of the H(+) ion in the stomach lumen is followed by binding of K(+) ion converting the pump conformation back to the E1 state (PubMed:7762614) (By similarity).|||The gastric H(+)/K(+) ATPase pump is composed of the catalytic alpha subunit ATP4A and the regulatory beta subunit ATP4B. Interacts (via the P-domain) with ATP4B (via N-terminus); this interaction stabilizes the lumenal-open E2 conformation state and prevents the reverse reaction of the transport cycle. http://togogenome.org/gene/10090:Ccar2 ^@ http://purl.uniprot.org/uniprot/Q8VDP4 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity.|||Component of the DBIRD complex (By similarity). Interacts with ZNF326/ZIRD; the interaction is direct (By similarity). Interacts (via N-terminus) with SIRT1, which inhibits the deacetylation of substrates (PubMed:21030595). Interacts (via N-terminus) with SUV39H1; this interaction abolishes the interaction with SIRT1 (PubMed:19218236). Component of a nuclear receptor-mediated transcription complex composed of at least ZNF335, CCAR2 and EMSY; the complex stimulates the transcription of nuclear receptor target genes such as SOX9 and HOXA1 (By similarity). Within the complex interacts with EMSY and interacts with ZNF335 (via C-terminus) (By similarity). Components of this complex may associate with components of a histone methylation complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (By similarity). Within this complex, interacts with ASH2L (By similarity). Interacts with NR1D1 (PubMed:23398316). Interacts (via N-terminus) with ESR1 and ESR2 (By similarity). Interacts (via N-terminus) with HDAC3 (via C-terminus) (PubMed:21030595). Interacts with HDAC1 and MED2F (PubMed:21030595). Interacts with MCC (By similarity). Interacts (via N-terminus) with NR1H2 and NR1H3 in a ligand-independent manner (By similarity). Interacts with CSNK2A1 (By similarity). Interacts (via N-terminus) with p53/TP53 (PubMed:25732823). Interacts (via N-terminus) with BRCA1 (via the BRCT domains) (By similarity). Interacts (via N-terminus) with CHEK2 (via protein kinase domain) (By similarity). Interacts with PSEM3 (By similarity). Interacts (via N-terminus) with PSIA3 and SENP1 (By similarity). The sumoylated form shows a preferential interaction with SIRT1 as compared to its unmodified form (By similarity).|||Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions (By similarity). Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis (By similarity). Inhibits SUV39H1 methyltransferase activity (PubMed:19218236). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (By similarity). Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress (By similarity). Regulates the circadian expression of the core clock components NR1D1 and BMAL1 (PubMed:23398316). Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (By similarity). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (By similarity). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (By similarity). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (By similarity). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (By similarity).|||Cytoplasm|||Genotoxic stress induces its sumoylation and sumoylation promotes the SIRT1-CCAR2 interaction which in turn inhibits SIRT1-mediated deacetylation of p53/TP53. Sumoylation leads to transcriptional activation of p53/TP53 by sequestering SIRT1 from p53/TP53. Desumoylated by SENP1.|||Mice mimic a fasted state and therefore, display an increased production of glucose. Display elevated levels of PCK1 and are glucose-intolerant in both a normal and a high-fat diet (PubMed:24415752). Mice develop more tumors including lymphomas, liver tumors, lung tumors (PubMed:25732823).|||Nucleus|||spindle http://togogenome.org/gene/10090:Syvn1 ^@ http://purl.uniprot.org/uniprot/Q9DBY1 ^@ Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated.|||Belongs to the HRD1 family.|||E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation (PubMed:12975321, PubMed:15611074). Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (PubMed:12975321, PubMed:15611074). Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis (PubMed:17170702). Required for embryogenesis (PubMed:15611074). Mediates the ubiquitination and subsequent degradation of cytoplasmic NFE2L1 (PubMed:21911472). During the early stage of B cell development, required for degradation of the pre-B cell receptor (pre-BCR) complex, hence supporting further differentiation into mature B cells (PubMed:29907570).|||Endoplasmic reticulum membrane|||Homodimer (By similarity). Interacts with p53/TP53 (PubMed:17170702). Interacts with HTT (By similarity). Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1 (PubMed:27064360) (By similarity). FAM8A1 is stabilized by interaction with SYNV1, which prevents its proteasomal degradation. OS9 and UBE2J1 recruitment to the complex may be mediated by SEL1L (By similarity). SYNV1 assembles with SEL1L and FAM8A1 through its transmembrane domains, but interaction with its cytoplasmic domain is required to confer stability to FAM8A1 and enhance recruitment of HERPUD1 (By similarity). The HRD1 complex also associates with VIMP and may transfer misfolded proteins from the endoplasmic reticulum to VCP (By similarity). May form a complex with ERLEC1; HSPA5; OS9 and SEL1L (By similarity). Interacts with VCP (By similarity). Interacts with UBXN6 (By similarity). Interacts with BAG6 (By similarity). Interacts with NFE2L1 (PubMed:21911472). Interacts (via N-terminus) with components of the pre-B cell receptor, including IGLL1 and VPREB1 (PubMed:29907570). Interacts with CREB3L3; this interaction leads to CREB3L3 ubiquitination and proteasomal degradation (PubMed:30389664).|||Mice overexpressing Syvn1 develop severe spontaneous arthropathy. Mice lacking Syvn1 die in utero around 13.5 dpc due to augmented apoptotic cell death.|||The RING-type zinc finger is required for E3 ligase activity.|||Up-regulated in conditions of cerebral ischemia (PubMed:15519674). In the liver, induced in postprandial conditions (PubMed:30389664).|||Widely expressed, with highest levels in bone, spleen, lung and testis. In the brain, present in neurons but not in glial cells. Up-regulated in synovial tissues from mice with collagen-induced arthritis (at protein level). Expressed in the liver (PubMed:30389664). http://togogenome.org/gene/10090:Med22 ^@ http://purl.uniprot.org/uniprot/Q62276 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 22 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Ccnt1 ^@ http://purl.uniprot.org/uniprot/Q9QWV9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylation on serine residues by PARP1 in response to DNA damage disrupts the phase separation activity of CCNT1, thereby preventing activation of CDK9.|||Belongs to the cyclin family. Cyclin C subfamily.|||Cyclin-T1 is the predominant cyclin that associates with CDK9 to form a heterodimer called P-TEFb (PubMed:27292648). P-TEFb forms a complex with AFF4/AF5Q31 (By similarity). Component of a complex which is at least composed of HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H, and NCL/nucleolin (By similarity). Component of the 7SK snRNP complex at least composed of P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, BCDIN3, SART3 proteins and 7SK and U6 snRNAs (By similarity). Interacts (via central region) with ZMYND8 (via N-terminus); the interaction is direct and the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (By similarity). Interacts with BRD4, targets chromatin binding (By similarity). Interacts with JMJD6 (By similarity). Interacts with MDFIC (By similarity). Interacts with HSF1. Interacts with HTATSF1 (By similarity). Interacts with TBX21 (PubMed:27292648).|||Nucleus|||Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II.|||The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance binding of the P-TEFb complex to the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). http://togogenome.org/gene/10090:Col16a1 ^@ http://purl.uniprot.org/uniprot/Q8BLX7 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 8 dpc no significant expression of mRNA or protein is observed, but strong signals are observed in placental trophoblasts. By 11 dpc weak positive signals are observed in heart. During later stages of development, stronger expression is observed in a variety of tissues, particularly in the atrial and ventricular walls of the developing heart, spinal root neural fibers and skin.|||Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.|||Expressed in most tissues examined with highest levels of expression observed in heart. Strongly expressed in cortical and medullar regions of kidney and more weakly expressed in lung. Also detected in the ciliary muscle of the eye, on the serosa layer lining the muscularis externa of intestinal tissue, and in the perimysium membrane lining both the cardiac muscle bundle and the smooth muscle tissue of the small intestine. Strongly stained in particulate or granular structures. Not detected in brain or skeletal muscle.|||Glycosylated.|||Homotrimer. Interacts with FBN1, fibronectin and integrins ITGA1/ITGB1 and ITGA2/ITGB1. Integrin ITGA1/ITGB1 binds to a unique site within COL16A1 located close to its C-terminal end between collagenous domains COL1-COL3 (By similarity).|||Involved in mediating cell attachment and inducing integrin-mediated cellular reactions, such as cell spreading and alterations in cell morphology.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||This sequence defines eighteen different domains, nine triple-helical domains (COL9 to COL1) and ten non-triple-helical domains (NC10 to NC1). The numerous interruptions in the triple helix may make this molecule either elastic or flexible.|||extracellular matrix http://togogenome.org/gene/10090:Anxa5 ^@ http://purl.uniprot.org/uniprot/P48036 ^@ Domain|||Function|||PTM|||Similarity|||Subunit ^@ A pair of annexin repeats may form one binding site for calcium and phospholipid.|||Belongs to the annexin family.|||Monomer. Binds ATRX and EIF5B (By similarity).|||S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.|||The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.|||This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. http://togogenome.org/gene/10090:Kcnk3 ^@ http://purl.uniprot.org/uniprot/O35111 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Cell membrane|||Homodimer. Heterodimer with KCNK1.|||Inactivated by barium.|||Very strong expression in heart, also detected in kidney, brain, skin, testis, lung, skeletal muscle, small intestine and stomach. Not detected in liver, thymus or spleen.|||pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward. http://togogenome.org/gene/10090:H2-Oa ^@ http://purl.uniprot.org/uniprot/B2RST7|||http://purl.uniprot.org/uniprot/Q9QWV1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Azin1 ^@ http://purl.uniprot.org/uniprot/O35484 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antizyme inhibitor (AZI) protein that positively regulates ornithine decarboxylase (ODC) activity and polyamine uptake. AZI is an enzymatically inactive ODC homolog that counteracts the negative effect of ODC antizymes (AZs) OAZ1, OAZ2 and OAZ3 on ODC activity by competing with ODC for antizyme-binding (PubMed:16916800, PubMed:18062773, PubMed:18508777). Inhibits antizyme-dependent ODC degradation and releases ODC monomers from their inactive complex with antizymes, leading to formation of the catalytically active ODC homodimer and restoring polyamine production (PubMed:10698696, PubMed:18062773, PubMed:18369191).|||Belongs to the Orn/Lys/Arg decarboxylase class-II family. ODC antizyme inhibitor subfamily.|||Expressed during testis development.|||Monomer (PubMed:18369191). Interacts with OAZ1 and OAZ3; this interaction disrupts the interaction between the antizyme and ODC1 (PubMed:18062773, PubMed:18369191).|||Nucleus|||Ubiquitinated, leading to its proteasomal degradation; a process that is reduced in presence of antizyme OAZ1. http://togogenome.org/gene/10090:Tmem117 ^@ http://purl.uniprot.org/uniprot/Q8BH18 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM117 family.|||Cell membrane|||Involved in endoplasmic reticulum (ER) stress-induced cell death pathway. http://togogenome.org/gene/10090:Sarm1 ^@ http://purl.uniprot.org/uniprot/Q6PDS3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Absence of Sarm1 provides a level of protection against axon degeneration (PubMed:22678360, PubMed:26912636, PubMed:28978465). Genetic deletion blocks Wallerian degeneration of sciatic nerve and cultured superior cervical ganglia and peripheral polyneuropathy induced by vincristine (PubMed:22678360, PubMed:27797810). Severed Sarm1 null axons are able to persist up to 72 hours after axotomy, whereas wild-type axons degenerate within 8 hours (PubMed:22678360). Similarly, axons appear to be protected from degeneration in a sciatic nerve lesion model, lasting up to 14 days compared with 3 days for wild type (PubMed:22678360). Mice display improved traumatic brain injury-associated phenotypes after injury: mice develop fewer beta-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury and show improved axonal integrity (PubMed:26912636). Mice show some protection against early but not late axonal degeneration in experimental allergic encephalomyelitis mouse model (PubMed:32584865). Mice exhibit normal glucose metabolism and pain sensitivity but show attenuated diabetic peripheral neuropathy (PubMed:31439642). Mice lacking both Sarm1 and Nmnat2 are viable and survive: Sarm1 deficiency corrects axon outgrowth in mice lacking Nmnat2, independently of NMNAT metabolites, preventing perinatal lethality (PubMed:25818290). Mice lacking both Rho and Sarm1 show a level of protection against retinal degeneration induced by the absence of Rho: the absence of Sarm1 promoting rod and cone photoreceptor cell survival (PubMed:32312889).|||Autoinhibited: in the inactive state, the enzymatic TIR domain is held apart by the autoinhibiting ARM repeats. NAD(+)-binding to ARM repeats maintains an inactive state by promoting interaction between ARM repeats and the TIR domain, thereby facilitating inhibition of the enzymatic TIR domain. Following activation, possibly by nicotinamide mononucleotide (NMN), auto-inhibitory interactions are released, allowing self-association of the TIR domains and subsequent activation of the NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is facilitated by the octamer of SAM domains.|||Belongs to the SARM1 family.|||Cytoplasm|||Down-regulated in sciatic nerve of mice with diabetic peripheral neuropathy (at protein level).|||Homooctamer; forms an octameric ring via SAM domains (By similarity). Interacts with TICAM1/TRIF and thereby interferes with TICAM1/TRIF function (By similarity). Interacts with SDC2 (via cytoplasmic domain) and MAPK10/JNK3 (PubMed:17724133, PubMed:21555464).|||Mitochondrion|||NAD(+) hydrolase, which plays a key role in axonal degeneration following injury by regulating NAD(+) metabolism (PubMed:25818290, PubMed:26686637, PubMed:27735788, PubMed:32312889). Acts as a negative regulator of MYD88- and TRIF-dependent toll-like receptor signaling pathway by promoting Wallerian degeneration, an injury-induced form of programmed subcellular death which involves degeneration of an axon distal to the injury site (PubMed:21555464, PubMed:22678360, PubMed:25818290, PubMed:26686637, PubMed:26423149). Wallerian degeneration is triggered by NAD(+) depletion: in response to injury, SARM1 is activated and catalyzes cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide; NAD(+) cleavage promoting cytoskeletal degradation and axon destruction (PubMed:28334607). Also able to hydrolyze NADP(+), but not other NAD(+)-related molecules (By similarity). Can activate neuronal cell death in response to stress (PubMed:19587044). Regulates dendritic arborization through the MAPK4-JNK pathway (PubMed:17724133, PubMed:21555464). Involved in innate immune response: inhibits both TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and the phosphorylation of MAPK14/p38 (PubMed:21555464).|||Phosphorylation at Ser-548 by JNK kinases (MAPK8, MAPK9 and /or MAPK10) enhance the NAD(+) hydrolase (NADase) activity. Phosphorylation at Ser-548 and subsequent activation takes place in response to oxidative stress conditions and inhibits mitochondrial respiration.|||Synapse|||The ARM repeats inhibit the NAD(+) hydrolase (NADase) activity by binding to NAD(+): NAD(+)-binding to ARM repeats facilitates inhibition of the TIR domain NADase through their domain interface. In contrast to classical ARM repeats, the last helix of ARM 6 does not fold back to interact with the first two helices, but instead turns towards the N-terminus of SARM1. As a result, the two following motifs ARM 7 and ARM 8 reverse their directions and lie perpendicularly. Moreover, ARM repeats interact with different domains not only within each protomer but also of the adjacent ones.|||The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.|||Widely expressed in the brain and neurons (at protein level) (PubMed:21555464). Expressed in photoreceptor cells of the neural retina (PubMed:32312889).|||axon|||dendrite http://togogenome.org/gene/10090:Fam110c ^@ http://purl.uniprot.org/uniprot/Q8VE94 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM110 family.|||Interacts with AKT1; the interaction is transient and follows AKT1 activation. Interacts with PPP2CA and alpha-tubulin.|||May play a role in microtubule organization. May play a role in cell spreading and cell migration of epithelial cells; the function may involve the AKT1 signaling pathway.|||Nucleus|||centrosome|||cytoskeleton|||spindle pole http://togogenome.org/gene/10090:Ccdc88a ^@ http://purl.uniprot.org/uniprot/Q5SNZ0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC88 family.|||Bifunctional modulator of guanine nucleotide-binding proteins (G proteins) (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits (By similarity). Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS (By similarity). Essential for cell migration (By similarity). Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration (By similarity). Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB (By similarity). Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (PubMed:15753085). Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (By similarity). Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (PubMed:19778506). Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation (By similarity). Essential for the integrity of the actin cytoskeleton (By similarity). Required for formation of actin stress fibers and lamellipodia (By similarity). May be involved in membrane sorting in the early endosome (By similarity). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (By similarity).|||CCDC88A knockout mice display mesial-temporal lobe epilepsy and early demise, and structural brain developmental defects affecting the corpus callosum and cerebrum.|||Cell membrane|||Cytoplasmic vesicle|||Expressed in the dentate gyrus, pyramidal cell layer of hippocampal regions CA1 and CA3 at postnatal 15. Expressed highly in neurons. Weakly in neuron progenitors (at protein level). Expressed in the dentate granule cell layer of the hippocampus. Expressed highly in the adult testis, moderately in the brain and at a low level in the spleen, lungs and fat.|||Homodimer (By similarity). Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunits GNAI1, GNAI2 and GNAI3 (By similarity). Also interacts (via GNA motif) with guanine nucleotide-binding protein G(s) alpha subunit GNAS (By similarity). Interaction with G(i) alpha subunits occurs before interaction with GNAS and is regulated by phosphorylation; phosphorylation at Ser-1677 enhances binding to G(i) alpha subunits while phosphorylation at Ser-1692 abolishes G(i) alpha subunit binding, promoting binding to GNAS (By similarity). Interacts (via C-terminal SH2-like region) with growth factor receptors EGFR, INSR and KDR/VEGFR2 (via their autophosphorylated cytoplasmic tails) (By similarity). Forms a complex with EGFR and GNAI3 which leads to enhanced EGFR signaling and triggering of cell migration; ligand stimulation is required for recruitment of GNAI3 to the complex (By similarity). Interacts (tyrosine-phosphorylated form) with phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a (via SH2 domains); the interaction enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration (By similarity). Interacts with serine/threonine-protein kinase PRKCQ; the interaction leads to phosphorylation of CCDC88A and inhibition of its guanine nucleotide exchange factor activity (By similarity). Interacts (via C-terminus) with DISC1; the interaction is direct (PubMed:19778506). Interacts with AKT proteins; the interaction is inhibited in the presence of DISC1 (PubMed:19778506). Interacts with AKT1/PKB (via C-terminus) (PubMed:15753085). The non-phosphorylated form interacts with phosphatidylinositol 4-phosphate [Pi(4)P] and weakly with phosphatidylinositol 3-phosphate [Pi(3)P] (By similarity). Interacts with microtubules (PubMed:15882442). Interacts with actin (By similarity).|||In the presence of tyrosine-autophosphorylated growth factor receptors, the C-terminus folds into an SH2-like region which promotes the stable recruitment of CCDC88A to the growth factor receptors. The SH2-like region is phosphorylated by the growth factor receptors prior to completion of folding.|||Phosphorylation is induced by epidermal growth factor (EGF) in a phosphoinositide 3-kinase (PI3K)-dependent manner (By similarity). Phosphorylation by AKT1/PKB is necessary for the delocalization from the cell membrane and for cell migration (By similarity). Phosphorylated on tyrosine residues which promotes binding to phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a and enhances PI3K activity (By similarity). Tyrosine-phosphorylated by both receptor and non-receptor tyrosine kinases in vitro (By similarity). Tyrosine phosphorylation is required for AKT1-dependent phosphorylation of Ser-1417 (By similarity). Phosphorylation at Ser-1692 by PRKCQ disrupts interaction with GNAI3 and inhibits guanine nucleotide exchange factor activity (By similarity).|||Temporally and spatially restricted during embryogenesis. At 10.5 dpc, expressed in the branchial arches, nasal processes, limbs, somites and dorsal root ganglia. At 11.5 dpc, expression persists at these sites in addition to the eye and fore-, mid- and hindbrain. By 12.5 dpc, expressed in the interdigital mesenchyme of the limbs. At 13.5 dpc, expression in the limbs flanks the digits and also appears in a subset of tendons in the hind- and forelimbs.|||The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).|||centriole|||cilium basal body|||cytosol|||lamellipodium http://togogenome.org/gene/10090:Ppp1r3f ^@ http://purl.uniprot.org/uniprot/Q9JIG4 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Glycogen-targeting subunit for protein phosphatase 1 (PP1).|||Highly expressed in brain (at protein level).|||Membrane http://togogenome.org/gene/10090:Babam2 ^@ http://purl.uniprot.org/uniprot/Q8K3W0 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BABAM2 family.|||Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1, BRCC3/BRCC36 and BABAM1/NBA1. Binds polyubiquitin. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BRCC3/BRCC36 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. May interact with FAS and TNFRSF1A (PubMed:9737713).|||Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Within the BRISC complex, acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. The BRISC complex plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination. May play a role in homeostasis or cellular differentiation in cells of neural, epithelial and germline origins (By similarity). May also act as a death receptor-associated anti-apoptotic protein, which inhibits the mitochondrial apoptotic pathway. May regulate TNF-alpha signaling through its interactions with TNFRSF1A; however these effects may be indirect (PubMed:9737713).|||Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. Probably also plays a role as a component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin (By similarity). May regulate TNF-alpha signaling through its interactions with TNFRSF1A.|||Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) regions. These regions lack the critical Cys residues required for ubiquitination but retain the ability to bind ubiquitin (By similarity).|||Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) regions. These regions lack the critical Cys residues required for ubiquitination but retain the ability to bind ubiquitin.|||Cytoplasm|||Expressed in brain, heart, kidney, liver, lung, testis, germinal center B-cells and various mouse cell lines.|||Nucleus|||Probable cloning artifact. http://togogenome.org/gene/10090:Apol10b ^@ http://purl.uniprot.org/uniprot/G3X9K7|||http://purl.uniprot.org/uniprot/Q8BZS1 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Or9g8 ^@ http://purl.uniprot.org/uniprot/Q7TR95 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam83a ^@ http://purl.uniprot.org/uniprot/Q8K2P2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM83 family.|||Cytoplasm|||Interacts with the regulatory subunit p85 of PI3-kinase; increased by EGFR activation. Interacts with RAF1; increased by EGFR activation it activates RAF1.|||Phosphorylated upon EGFR activation.|||Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both RAS/MAPK and PI3K/AKT/TOR signaling cascades downstream of EGFR. Required for the RAS/MAPK signaling cascade activation upon EGFR stimulation, it also activates both signaling cascades independently of EGFR activation. http://togogenome.org/gene/10090:Ccdc80 ^@ http://purl.uniprot.org/uniprot/Q8R2G6 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CCDC80 family.|||Binds to various extracellular matrix proteins.|||Expressed in brain, stomach, colon, rectum, liver, lung, kidney, adipocytes and testis.|||Expressed in embryo at 7 dpc onwards. Expressed in rib, sternal cartilage, heart, kidney, leg muscles, intestine and limb at 7 dpc. Expressed in chondrocytes at 14.5 dpc. Expressed in cartilage at 14 dpc. Present in rib cartilage and choroid plexus epithelium at 16.5 dpc (at protein level).|||Phosphorylated.|||Promotes cell adhesion and matrix assembly.|||Up-regulated in adipose tissue of obese BRS-3-deficient mice.|||extracellular matrix http://togogenome.org/gene/10090:Rps27l ^@ http://purl.uniprot.org/uniprot/D3YYB0|||http://purl.uniprot.org/uniprot/Q6ZWY3 ^@ Cofactor|||Similarity ^@ Belongs to the eukaryotic ribosomal protein eS27 family.|||Binds 1 zinc ion per subunit. http://togogenome.org/gene/10090:Cfap299 ^@ http://purl.uniprot.org/uniprot/Q810M1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed in testis, specifically in spermatogonia and primary spermatocytes but not in secondary spermatocytes and spermatids.|||Cytoplasm|||First detected in testis in two week old mice; expression continuously increases in testis from 2 to 8 weeks after birth and remains at a constant level in 6-month-old testis.|||May be involved in spermatogenesis.|||Nucleus http://togogenome.org/gene/10090:Fggy ^@ http://purl.uniprot.org/uniprot/A2AJL3 ^@ Function|||Similarity ^@ Belongs to the FGGY kinase family.|||Catalyzes ATP-dependent phosphorylation of D-ribulose at C-5 to form D-ribulose 5-phosphate. Postulated to function in a metabolite repair mechanism by preventing toxic accumulation of free D-ribulose formed by non-specific phosphatase activities. Alternatively, may play a role in regulating D-ribulose 5-phosphate recycling in the pentose phosphate pathway. Can phosphorylate ribitol with low efficiency. http://togogenome.org/gene/10090:Mmp21 ^@ http://purl.uniprot.org/uniprot/Q3KP73|||http://purl.uniprot.org/uniprot/Q3KP74|||http://purl.uniprot.org/uniprot/Q8K3F2 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||Plays a specialized role in the generation of left-right asymmetry during embryogenesis (PubMed:26437028). May act as a negative regulator of the NOTCH-signaling pathway. Cleaves alpha-1-antitrypsin (By similarity).|||Secreted|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase. http://togogenome.org/gene/10090:Ptk2b ^@ http://purl.uniprot.org/uniprot/E9Q2A6|||http://purl.uniprot.org/uniprot/K7QD41|||http://purl.uniprot.org/uniprot/Q3UDE9|||http://purl.uniprot.org/uniprot/Q9QVP9 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated in response to stimuli that lead to increased intracellular Ca(2+) levels; this activation is indirect and may be mediated by calcium-mediated production of reactive oxygen species (ROS). Activated by autophosphorylation at Tyr-402; this creates a binding site for SRC family kinases and leads to phosphorylation at additional tyrosine residues. Phosphorylation at Tyr-402, Tyr-579 and Tyr-580 is required for optimal kinase activity.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.|||Cell membrane|||Cytoplasm|||Homodimer, or homooligomer. Interacts with KCNA2 (By similarity). Interacts with NPHP1, ASAP1, ASAP2, ARHGAP26, SKAP2 and TGFB1I1. The Tyr-402 phosphorylated form interacts with SRC (via SH2 domain) and SRC family members. Forms a signaling complex with EPHA1, LCK and phosphatidylinositol 3-kinase; upon activation by EFNA1. Interacts with GRB2 (via SH2 domain). Interacts with P53/TP53 and MDM2. Interacts with MYLK. Interacts with BCAR1. Interacts with RB1CC1. Interacts with RHOU. Interacts with VAV1. Interacts with PDPK1. Interacts with DLG4. Interacts with LPXN and PTPN12. Interacts with SIRPA and SH2D3C. Interacts (hypophosphorylated) with PXN. Interacts with ARHGAP10.|||Mice are born at the expected Mendelian rate, appear normal and are fertile. Mice display increased bone formation and high bone mass, due to defects in osteoclastic bone resorption. Osteoclasts display defects in actin cytoskeleton reorganization, plus altered Rho activity, microtubule stabilization and podosome organization. Mice also display increased differentiation and activity of osteoprogenitor cells. Macrophages from mutant mice display defects in their responses to chemokines, including defects in cell polarization, actin cytoskeleton reorganization, directed migration towards sites of inflammation, but also defects in the regulation of intracellular Ca(2+) levels, phosphatidylinositol 3-kinase activity and inositol 1,4,5-trisphosphate production. Mutant mice have normal B-cell polulations in bone marrow, lymph nodes and blood, but lack marginal zone B-cells in the spleen.|||Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376' (By similarity). Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2 (By similarity).|||Nucleus|||Phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration; this activation is indirect and may be mediated by production of reactive oxygen species (ROS). Tyr-402 is the major autophosphorylation site, but other kinases can also phosphorylate Tyr-402. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-402 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-579; Tyr-580 and Tyr-881. Phosphorylation at Tyr-881 is important for interaction with GRB2. Phosphorylated on tyrosine residues upon activation of FGR and PKC. Recruitment by NPHP1 to cell matrix adhesions initiates Tyr-402 phosphorylation. In monocytes, adherence to substrata is required for tyrosine phosphorylation and kinase activation. Angiotensin II, thapsigargin and L-alpha-lysophosphatidic acid (LPA) also induce autophosphorylation and increase kinase activity. Phosphorylation by MYLK promotes ITGB2 activation and is thus essential to trigger neutrophil transmigration during lung injury. Dephosphorylated by PTPN12 (By similarity).|||cell cortex|||focal adhesion|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Apip ^@ http://purl.uniprot.org/uniprot/Q9WVQ5 ^@ Cofactor|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldolase class II family. MtnB subfamily.|||Binds 1 zinc ion per subunit.|||Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death.|||Cytoplasm|||Expressed in skeletal muscle (at protein level).|||Homotetramer. Interacts with APAF1. May interact with CASP1.|||Up-regulated upon ischemia/hypoxia. http://togogenome.org/gene/10090:Kcnj14 ^@ http://purl.uniprot.org/uniprot/Q8JZN3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ14 subfamily.|||Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ14 gives rise to low-conductance channels with a low affinity to the channel blockers Barium and Cesium (By similarity).|||Membrane http://togogenome.org/gene/10090:Cyc1 ^@ http://purl.uniprot.org/uniprot/Q9D0M3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c family.|||Binds 1 heme c group covalently per subunit.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding.|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. Cytochrome c1 is a catalytic core subunit containing a c-type heme. It transfers electrons from the [2Fe-2S] iron-sulfur cluster of the Rieske protein to cytochrome c.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Aunip ^@ http://purl.uniprot.org/uniprot/E9Q6Z5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AUNIP family.|||Chromosome|||DNA-binding protein that accumulates at DNA double-strand breaks (DSBs) following DNA damage and promotes DNA resection and homologous recombination. Serves as a sensor of DNA damage: binds DNA with a strong preference for DNA substrates that mimic structures generated at stalled replication forks, and anchors RBBP8/CtIP to DSB sites to promote DNA end resection and ensuing homologous recombination repair. Inhibits non-homologous end joining (NHEJ). Required for the dynamic movement of AURKA at the centrosomes and spindle apparatus during the cell cycle.|||Interacts (via C-terminus) with AURKA (via C-terminus). Interacts (via N-terminus) with NIN; this interaction blocks NIN phosphorylation by both AURKA and GSK3B. Identified in a complex with NIN and AURKA. Interacts with RBBP8/CtIP.|||Nucleus|||centrosome|||spindle pole http://togogenome.org/gene/10090:Or9i1b ^@ http://purl.uniprot.org/uniprot/Q7TQQ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cdan1 ^@ http://purl.uniprot.org/uniprot/Q8CC12 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Embryonic lethal; embryos die before 7.5 days of gestation.|||Expressed ubiquitously during early embryogenesis.|||Interacts with ASF1A and ASF1B. Found in a cytosolic complex with ASF1A, ASF1B, IPO4 and histones H3.1 and H4.|||May act as a negative regulator of ASF1 in chromatin assembly.|||Membrane|||Nucleus|||Widely expressed in adult mice, the highest levels can be measured in erythropoietic cells. http://togogenome.org/gene/10090:Nudt18 ^@ http://purl.uniprot.org/uniprot/Q3U2V3 ^@ Function|||Similarity ^@ Belongs to the Nudix hydrolase family.|||Mediates the hydrolysis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal hydrolysis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and GDP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools (By similarity). http://togogenome.org/gene/10090:Ssu2 ^@ http://purl.uniprot.org/uniprot/Q8C3L1 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||In the developing brain, expressed at low levels prior to 15 dpc. Expression increases in the early postnatal stages, peaks at P16, and decreases in adulthood.|||Nucleus|||Plays a role in odontogenesis.|||Widely expressed, with highest levels in the liver, intestine, tongue and underjaw. http://togogenome.org/gene/10090:Ppp1cb ^@ http://purl.uniprot.org/uniprot/P62141 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PPP phosphatase family. PP-1 subfamily.|||Binds 2 manganese ions per subunit.|||Cytoplasm|||Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress (By similarity).|||Nucleus|||PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. The targeting or regulatory subunits determine the substrate specificity of PP1. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R7 and PPP1R12C. Interacts with PPP1R12A and NUAK1; the interaction is direct. Interacts with TRIM28; the interaction is weak (By similarity). Interacts with PPP1R15A; the interaction mediates binding to EIF2S1. Interacts with PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with TRIM28; the interaction is weak (By similarity). Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PPP1R15B; the interaction mediates binding to EIF2S1. Interacts with FOXP3 (By similarity). Interacts with RRP1B (By similarity). Interacts with SERPINE1. Interacts with LZTR1 (By similarity).|||Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:F2r ^@ http://purl.uniprot.org/uniprot/P30558 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis.|||Phosphorylated in the C-terminal tail; probably mediating desensitization prior to the uncoupling and internalization of the receptor.|||Proteolytic cleavage by thrombin generates a new N-terminus that functions as a tethered ligand. Also proteolytically cleaved by cathepsin CTSG.|||The cleaved signal peptide may not be degraded and may function as an intracellular angiogenesis inhibitor peptide known as parstatin. http://togogenome.org/gene/10090:Gak ^@ http://purl.uniprot.org/uniprot/Q99KY4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1 (By similarity).|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||focal adhesion|||perinuclear region|||trans-Golgi network http://togogenome.org/gene/10090:Plcd3 ^@ http://purl.uniprot.org/uniprot/Q8K2J0 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.|||Cleavage furrow|||Cytoplasm|||Expressed in cerebellum and cerebral cortex.|||Expression increases during embryonic or postnatal brain development from cerebral cortex at 14 dpc to P7 stage.|||Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca(2+) from intracellular stores. Essential for trophoblast and placental development. May participate in cytokinesis by hydrolyzing PIP2 at the cleavage furrow. Regulates neurite outgrowth through the inhibition of RhoA/Rho kinase signaling (PubMed:21187285).|||Intron retention.|||Membrane|||Mice lacking Plcd1 and Plcd3 die between 11.5 and 13.5 dpc. They exhibit severe disruption of the normal labyrinth architecture in the placenta and decreased placental vascularization, as well as abnormal proliferation and apoptosis of trophoblasts in the labyrinth area. Furthermore, Plcd1 and Plcd3 double knockout embryos supplied with a normal placenta by the tetraploid aggregation method survive beyond 14.5 dpc, indicating that the embryonic lethality is caused by a defect in trophoblasts.|||Strongly activated by phosphatidic acid. Inhibited by phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), sphingomyelin and phosphatidylserine (PtdSer) (By similarity).|||The C2 domain is a Ca(2+)-dependent membrane-targeting module.|||The PH domain mediates interaction with the surface membrane by binding to PIP2. http://togogenome.org/gene/10090:Srxn1 ^@ http://purl.uniprot.org/uniprot/A2AQU8|||http://purl.uniprot.org/uniprot/Q9D975 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfiredoxin family.|||Contributes to oxidative stress resistance by reducing cysteine-sulfinic acid formed under exposure to oxidants in the peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4. Does not act on PRDX5 or PRDX6. May catalyze the reduction in a multi-step process by acting both as a specific phosphotransferase and a thioltransferase.|||Cytoplasm http://togogenome.org/gene/10090:Zfp628 ^@ http://purl.uniprot.org/uniprot/Q8CJ78 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During development, expression in the brain decreases gradually (PubMed:15556296). Shows increasing expression in testis from 16.5 dpc onwards, with maximum expression at postnatal day 21 (PubMed:31932482).|||Expressed widely in testis, in both germline and somatic cells (PubMed:31932482). Seems to have particularly strong expression in meiotic spermatocytes, postmeiotic round spermatids and Sertoli cells (PubMed:31932482). Not detected in elongating spermatids or mature sperm (at protein level) (PubMed:31932482). Expressed in testis, ovary, spleen, lung, brain, liver and kidney (PubMed:15556296, PubMed:31932482). Expressed in D3 embryonic stem cells and F9 embryonal carcinoma cells (PubMed:15556296).|||Interacts with TAF4B.|||Nucleus|||Transcriptional activator (PubMed:15556296, PubMed:31932482). Binds DNA on GT-box consensus sequence 5'-TTGGTT-3' (PubMed:15556296). Plays a role in spermiogenesis (PubMed:31932482).|||Viable, with no gross morphological or behavioral phenotypes. Males are infertile with complete absence of mature sperm. Spermiogenesis arrests at the round spermatid stage, accompanied by extensive apoptosis within the seminiferous tubules. Expression of spermiogenesis-associated genes TNP1, TNP2, PRM1 and PRM2 in testis is significantly reduced. http://togogenome.org/gene/10090:Exoc4 ^@ http://purl.uniprot.org/uniprot/O35382|||http://purl.uniprot.org/uniprot/Q9CXE1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SEC8 family.|||Cell projection|||Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.|||Expressed in the striatum (at protein level).|||Midbody ring|||The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8 (By similarity). Interacts with BIRC6/bruce (By similarity). Interacts with MYRIP. Interacts with SH3BP1; required for the localization of both SH3BP1 and the exocyst to the leading edge of migrating cells (By similarity). Interacts with SLC6A9 (By similarity).|||centrosome http://togogenome.org/gene/10090:Pcsk9 ^@ http://purl.uniprot.org/uniprot/Q80W65 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S8 family.|||Cell surface|||Cleavage by furin and PCSK5 generates a truncated inactive protein that is unable to induce LDLR degradation.|||Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.|||Cytoplasm|||Down-regulated following a high-cholesterol diet.|||Endoplasmic reticulum|||Endosome|||Golgi apparatus|||Hepatocytes, kidney mesenchymal cells, intestinal ileum, colon epithelia and embryonic brain telencephalon neurons.|||In the embryo, expressed in the liver at 9 dpc, in the skin and transiently in the telencephalon at 12 dpc, and in the kidney, small intestine and cerebellum at 15 dpc.|||Its proteolytic activity is autoinhibited by the non-covalent binding of the propeptide to the catalytic domain. Inhibited by EGTA.|||Lysosome|||Monomer. Can self-associate to form dimers and higher multimers which may have increased LDLR degrading activity. The precursor protein but not the mature protein may form multimers. Interacts with APOB, VLDLR, LRP8/APOER2 and BACE1. The full-length immature form (pro-PCSK9) interacts with SCNN1A, SCNN1B and SCNN1G. The pro-PCSK9 form (via C-terminal domain) interacts with LDLR. Interacts (via the C-terminal domain) with ANXA2 (via repeat Annexin 1); the interaction inhibits the degradation of LDLR.|||Phosphorylation protects the propeptide against proteolysis.|||Secreted|||The C-terminal domain (CRD) is essential for the LDLR-binding and degrading activities.|||The catalytic domain is responsible for mediating its self-association.|||Undergoes autocatalytic cleavage in the endoplasmic reticulum to release the propeptide from the N-terminus and the cleavage of the propeptide is strictly required for its maturation and activation. The cleaved propeptide however remains associated with the catalytic domain through non-covalent interactions, preventing potential substrates from accessing its active site. As a result, it is secreted from cells as a propeptide-containing, enzymatically inactive protein (By similarity). http://togogenome.org/gene/10090:Osmr ^@ http://purl.uniprot.org/uniprot/A0A0R4J268|||http://purl.uniprot.org/uniprot/G3X8V6|||http://purl.uniprot.org/uniprot/O70458 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with IL31RA to form the IL31 receptor (PubMed:9920829). Binds IL31 to activate STAT3 and possibly STAT1 and STAT5 (By similarity). Capable of transducing OSM-specific signaling events (By similarity).|||Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Heterodimer composed of OSMR and IL6ST (type II OSM receptor). Heterodimer with IL31RA to form the IL31 receptor.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||Up-regulated by IL31 in dorsal root ganglia.|||Widely expressed (PubMed:9584176). Expressed at highest levels in the lung, heart, thymus and spleen (PubMed:9920829). Expressed in dorsal root ganglia (PubMed:25381841). http://togogenome.org/gene/10090:Angel1 ^@ http://purl.uniprot.org/uniprot/Q8VCU0 ^@ Similarity ^@ Belongs to the CCR4/nocturin family. http://togogenome.org/gene/10090:Trappc9 ^@ http://purl.uniprot.org/uniprot/E9Q3T8|||http://purl.uniprot.org/uniprot/Q3U0M1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NIBP family.|||Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12 (By similarity). Directly interacts with IKBKB and MAP3K14.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in neurons of the pyramidal layer of the cortex, in spinal cord motor neurons and white matter neurons (at protein level).|||Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex. May function in neuronal cells differentiation. May play a role in vesicular transport from endoplasmic reticulum to Golgi.|||cis-Golgi network http://togogenome.org/gene/10090:Tpm4 ^@ http://purl.uniprot.org/uniprot/Q6IRU2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tropomyosin family.|||Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. Binds calcium.|||Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain.|||The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.|||cytoskeleton http://togogenome.org/gene/10090:Itfg1 ^@ http://purl.uniprot.org/uniprot/Q99KW9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TIP family.|||Interacts with RUVBL1, RUVBL2 and alpha-tubulin.|||Membrane|||Modulator of T-cell function. Has a protective effect in graft versus host disease model.|||Secreted http://togogenome.org/gene/10090:Npff ^@ http://purl.uniprot.org/uniprot/Q9WVA8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FARP (FMRFamide related peptide) family.|||Morphine modulating peptides. Have wide-ranging physiologic effects, including the modulation of morphine-induced analgesia, elevation of arterial blood pressure, and increased somatostatin secretion from the pancreas. Neuropeptide FF potentiates and sensitizes ASIC1 and ASIC3 channels.|||Secreted http://togogenome.org/gene/10090:Or5b12b ^@ http://purl.uniprot.org/uniprot/Q8VFW9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Kri1 ^@ http://purl.uniprot.org/uniprot/F6WIU1 ^@ Similarity ^@ Belongs to the KRI1 family. http://togogenome.org/gene/10090:Pbx2 ^@ http://purl.uniprot.org/uniprot/O35984|||http://purl.uniprot.org/uniprot/Q4FJL3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TALE/PBX homeobox family.|||Forms heterodimers with MEIS1 and heterotrimers with MEIS1 and HOXA9. Interacts with PBXIP1 (By similarity).|||Nucleus|||Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1 (By similarity). http://togogenome.org/gene/10090:Notch1 ^@ http://purl.uniprot.org/uniprot/Q01705 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NOTCH family.|||Cell membrane|||First detected in the mesoderm at 7.5 dpc By 8.5 dpc highly expressed in presomitic mesoderm, mesenchyme and endothelial cells, while much lower levels are seen in the neuroepithelium. Between 9.5-10.5 dpc expressed at high levels in the neuroepithelium. At 13.5 dpc expressed in the surface ectoderm, eye and developing whisker follicles. Hair follicle matrix cells expression starts as different cell types become distinguishable in the developing follicle. Expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level expression are in transition from mitotic precursors to several discrete, differentiating cell types. Specifically expressed in cerebellar Bergmann glial cells during postnatal development.|||Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).|||Heterodimer of a C-terminal fragment N(TM) and an N-terminal fragment N(EC) which are probably linked by disulfide bonds. Interacts with DNER, DTX1, DTX2 and RBPJ/RBPSUH. Also interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH1. Notch 1 intracellular domain interacts with SNW1; the interaction involves multimerized NOTCH1 NICD and is implicated in a formation of an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ. The activated membrane-bound form interacts with AAK1 which promotes NOTCH1 stabilization. Forms a trimeric complex with FBXW7 and SGK1. Interacts with HIF1AN. HIF1AN negatively regulates the function of notch intracellular domain (NICD), accelerating myogenic differentiation. Interacts (via NICD) with SNAI1 (via zinc fingers); the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts (via NICD) with MDM2A. Interacts (via NICD) with BCL6; the interaction decreases MAML1 recruitment by NOTCH1 NICD on target genes DNA and inhibits NOTCH1 transcractivation activity. Interacts with THBS4. Interacts (via the EGF-like repeat region) with CCN3 (via CTCK domain) (PubMed:12050162). Interacts (via EGF-like domains) with DLL4 (via N-terminal DSL and MNNL domains) (By similarity). Interacts with ZMIZ1. Interacts (via NICD domain) with MEGF10 (via the cytoplasmic domain) (PubMed:28498977). Interacts with DLL1 and JAG1 (PubMed:28089369). Interacts (via NICD domain) with PRAG1 (PubMed:25038227). Forms a complex with PRAG1, N1ICD and MAML1, in a MAML1-dependent manner (PubMed:25038227). Interacts (via transmembrane region) with PSEN1; the interaction is direct (By similarity). Interacts with ZFP64 (PubMed:18430783).|||Highly expressed in the brain, lung and thymus. Expressed at lower levels in the spleen, bone-marrow, spinal cord, eyes, mammary gland, liver, intestine, skeletal muscle, kidney and heart. In the hair follicle, highly expressed exclusively in the epithelial compartment.|||Hydroxylated at Asn-1945 and Asn-2012 by HIF1AN. Hydroxylation reduces affinity for HI1AN and may thus indirectly modulate negative regulation of NICD.|||Interaction with PSEN1 causes partial unwinding of the transmembrane helix, facilitating access to the scissile peptide bond.|||Nucleus|||O-linked glycosylation by GALNT11 is involved in determination of left/right symmetry: glycosylation promotes activation of NOTCH1, possibly by promoting cleavage by ADAM17, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO) (By similarity). O-glycosylated on the EGF-like domains (PubMed:21757702). O-glucosylated at Ser-435 by KDELC1 and KDELC2 (PubMed:30127001). Contains both O-linked fucose and O-linked glucose in the EGF-like domains 11, 12 and 13, which are interacting with the residues on DLL4 (By similarity). O-glycosylation at Ser-1027 is only partial (PubMed:21757702). MFNG-, RFNG- and LFNG-mediated modification of O-fucose residues at specific EGF-like domains results in inhibition of its activation by JAG1 and enhancement of its activation by DLL1 via an increased binding to DLL1 (PubMed:28089369).|||Phosphorylated.|||Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form (PubMed:10882062, PubMed:10882063). Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by ADAM17 to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT) (PubMed:10882062, PubMed:10882063). Following endocytosis, this fragment is then cleaved by one of the catalytic subunits of gamma-secretase (PSEN1 or PSEN2) to release a Notch-derived peptide containing the intracellular domain (NICD) from the membrane (PubMed:10882062, PubMed:11518718, PubMed:11459941).|||Ubiquitinated. Undergoes 'Lys-29'-linked polyubiquitination by ITCH; promotes the lysosomal degradation of non-activated internalized NOTCH1 (PubMed:18628966, PubMed:23886940). Monoubiquitination at Lys-1749 is required for activation by gamma-secretase cleavage, it promotes interaction with AAK1, which stabilizes it. Deubiquitination by EIF3F is necessary for nuclear import of activated Notch (PubMed:15240571). http://togogenome.org/gene/10090:Nfkbia ^@ http://purl.uniprot.org/uniprot/Q9Z1E3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NF-kappa-B inhibitor family.|||Cytoplasm|||Highly expressed in lymph node, thymus followed by liver, brain, muscle, kidney, gastrointestinal and reproductive tract.|||Hydroxylated by HIF1AN.|||Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:10097128, PubMed:9990853). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7878466, PubMed:10097128, PubMed:9990853).|||Interacts with RELA; the interaction requires the nuclear import signal (By similarity). Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (By similarity). Interacts with NKIRAS1 and NKIRAS2 (By similarity). Interacts with RWDD3; the interaction enhances sumoylation (By similarity). Interacts with PRMT2 (By similarity). Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen (By similarity). Interacts with MEFV (By similarity). Interacts with DDRGK1; positively regulates NFKBIA phosphorylation and degradation (By similarity).|||Nucleus|||Phosphorylated at Ser-32 and Ser-36 by IKKA/CHUK and IKKB/IKBKB; disables inhibition of NF-kappa-B DNA-binding activity (PubMed:7878466, PubMed:9859996, PubMed:9990853, PubMed:10097128). Phosphorylation at positions 32 and 36 is prerequisite to recognition by the SCF(FBXW11) and SCF(BTRC) complexes, leading to polyubiquitination and subsequent degradation (PubMed:9859996, PubMed:10097128).|||Polyubiquitinated at Lys-21 and/or Lys-22 following phosphorylation at Ser-32 and Ser-36 (PubMed:9990853). Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3 (By similarity). Ubiquitin chain elongation is then performed by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin (By similarity). The resulting polyubiquitination leads to protein degradation (By similarity). Also ubiquitinated by the SCF(BTRC) complex following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By similarity). Deubiquitinated by USP38, leading to NF-kappa-B inhibition (By similarity).|||Sumoylated; sumoylation requires the presence of the nuclear import signal. Sumoylation blocks ubiquitination and proteasome-mediated degradation of the protein thereby increasing the protein stability. http://togogenome.org/gene/10090:C1qtnf4 ^@ http://purl.uniprot.org/uniprot/Q8R066 ^@ Caution|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ High expression in testis, kidney, and brain. Expressed in brain and kidney (at protein level). Within the brain, highly expressed in cerebellum, cortex, hippocampus and hypothalamus, and lower expression in hindbrain (at protein level). Serum levels were increased in leptin-deficient ob/ob mice (a genetic model of hyperphagia and morbid obesity) relative to age-matched lean controls. No difference in serum levels were detected between mice fed a low-fat versus high-fat diet for 14 weeks (PubMed:24366864).|||Homomultimer. Forms trimers, hexamers and high molecular weight oligomers.|||Involvement in food intake and energy was only observed when the protein was externally administered in the brain, but not when this protein was overexpressed in vivo (PubMed:24366864).|||May be involved in the regulation of the inflammatory network. The role as pro- or anti-inflammatory seems to be context dependent (By similarity). Seems to have some role in regulating food intake and energy balance when administered in the brain. This effect is sustained over a two-day period, and it is accompanied by decreased expression of orexigenic neuropeptides in the hypothalamus 3 hours post-injection (Probable).|||Secreted|||There are conflicting results in its involvement in the inflammatory network. It was first described to be a pro-inflammatory cytokine by inducing the activation of NF-kappa-B signaling pathway and up-regulates IL6 production in liver carcinoma cells. While it seems to have the opposite effect in macrophages.|||Up-regulated during acute colitis induced by injection of dextran sulfate sodium (DSS). http://togogenome.org/gene/10090:Rnf186 ^@ http://purl.uniprot.org/uniprot/Q9D241 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ E3 ubiquitin protein ligase that is part of an apoptotic signaling pathway activated by endoplasmic reticulum stress. Stimulates the expression of proteins specific of the unfolded protein response (UPR), ubiquitinates BNIP1 and regulates its localization to the mitochondrion and induces calcium release from the endoplasmic reticulum that ultimately leads to cell apoptosis. Plays a role in the maintenance of intestinal homeostasis and clearance of enteric pathogens (PubMed:34623328). Upon NOD2 stimulation, ubiquitinates the ER stress sensor activating transcription factor 6/ATF6 and promotes the unfolded protein response UPR. Participates in basal level of autophagy maintenance by regulating the ubiquitination of EPHB2. Upon stimulation by ligand EFNB1, ubiquitinates EPHB2 and further recruits MAP1LC3B for autophagy induction (PubMed:33280498). Controls nutrient sensing by ubiquitinating Sestrin-2/SESN2, which is an intracellular sensor of cytosolic leucine and inhibitor of mTORC1 activity.|||Endoplasmic reticulum membrane|||Interacts with BNIP1.|||Mutant deletion mice demonstrate an increased bacterial burden in the mesenteric lymph nodes and spleen compared with WT mice (PubMed:34623328). They have also a more severe phenotype in the dextran sodium sulfate-induced colitis model, which is due to a defect in autophagy in colon epithelial cells (PubMed:33280498).|||Polyubiquitinated. 'Lys-29'-linked autoubiquitination leads to proteasomal degradation.|||The RING-type domain is required for ubiquitination. http://togogenome.org/gene/10090:Sorcs1 ^@ http://purl.uniprot.org/uniprot/A0A1B0GRC4|||http://purl.uniprot.org/uniprot/A0A1B0GRN1|||http://purl.uniprot.org/uniprot/A0A1B0GT94|||http://purl.uniprot.org/uniprot/Q8BSV0 ^@ Similarity ^@ Belongs to the VPS10-related sortilin family. SORCS subfamily. http://togogenome.org/gene/10090:Nxnl2 ^@ http://purl.uniprot.org/uniprot/Q9D531 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ At 10 months of age, mutant animals show signs of photoreceptor dysfunction. The progressive loss of cone function is followed by cone cell death, while in rods, the outer segment length id reduced, but not rod cell death is not observed. At 12 months, mice present a stronger age-dependent impairment of fine odor discrimination than their wild-type counterparts.|||Belongs to the nucleoredoxin family.|||Both isoforms are expressed in retina, in the photoreceptor layer, and throughout the olfactory sensory neuron layer of the nasal epithelium, in neurons. Also expressed at low levels in brain and testis.|||May be involved in the maintenance of both the function and the viability of sensory neurons, including photoreceptors and olfactory neurons. In the retina, isoform 1 may be required for rod function and isoform 2 for cone viability and function. http://togogenome.org/gene/10090:Slc66a1 ^@ http://purl.uniprot.org/uniprot/A6PWV7|||http://purl.uniprot.org/uniprot/Q8C4N4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Amino acid transporter that specifically mediates the pH-dependent export of the cationic amino acids arginine, histidine and lysine from lysosomes.|||Belongs to the laat-1 family.|||Lysosome membrane|||Membrane|||The di-leucine motif mediates lysosomal localization.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Adam5 ^@ http://purl.uniprot.org/uniprot/Q3TTE0 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in sperm (at protein level) (PubMed:20945367). Highly expressed in testis (PubMed:7750654). Expressed in the brain, kidney, liver, lung, spleen and ovary (PubMed:7750654).|||Interacts with TEX101.|||Membrane|||Not expected to have protease activity.|||Subject to proteolytic processing during epididymal transit of spermatozoa.|||This is a non catalytic metalloprotease-like protein. May play a role in sperm-egg fusion (By similarity). http://togogenome.org/gene/10090:Slc15a1 ^@ http://purl.uniprot.org/uniprot/Q14BA3|||http://purl.uniprot.org/uniprot/Q3UWE2|||http://purl.uniprot.org/uniprot/Q9JIP7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Apical cell membrane|||Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.|||Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1 (PubMed:11004485) (By similarity). Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (By similarity). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system (By similarity).|||Interacts (via extracellular domain region) with trypsin.|||Membrane|||The extracellular domain (ECD) region specifically binds trypsin. http://togogenome.org/gene/10090:Slain2 ^@ http://purl.uniprot.org/uniprot/Q8CI08 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SLAIN motif-containing family.|||Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Promotes cytoplasmic microtubule nucleation and elongation. Required for normal structure of the microtubule cytoskeleton during interphase.|||Contaminating sequence. Potential poly-A sequence.|||Contaminating sequence. Potential vector sequence.|||Interacts with CLIP1, CLIP2, CKAP5, CLASP1, MAPRE1 and MAPRE3.|||Is highly phosphorylated during mitosis, but not during interphase. The highly phosphorylated form does not localize at microtubule plus ends and does not interact with MAPRE1 or CKAP5 (By similarity).|||The N-terminus forms a two-stranded coiled coil.|||cytoskeleton http://togogenome.org/gene/10090:Ebi3 ^@ http://purl.uniprot.org/uniprot/O35228 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with IL27 to form the IL-27 interleukin, a heterodimeric cytokine which functions in innate immunity. IL-27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that has diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17). It drives rapid clonal expansion of naive but not memory CD4 T-cells. It also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines.|||Belongs to the type I cytokine receptor family. Type 3 subfamily.|||Heterodimer with IL27/IL27A; not disulfide-linked. This heterodimer is known as interleukin IL-27. Heterodimer with IL12A; not disulfide-linked. This heterodimer is known as interleukin IL-35. Interacts with SQSTM1.|||Secreted http://togogenome.org/gene/10090:Ctf2 ^@ http://purl.uniprot.org/uniprot/P83714|||http://purl.uniprot.org/uniprot/Q0VB69 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-6 superfamily.|||Binds to tripartite CNTF receptor complex consisting of CNTF alpha chain, LIFR and IL6ST (in vitro).|||Expressed in embryonic life, with a dramatic peak at day 11 of gestation. At 10 dpc, it is prominently expressed in cells scattered throughout all neuroepithelia, it is also detectable in cranial and dorsal root sensory ganglia, and spinal cord. At 14 dpc, outside the nervous system, it is detectable in vibrissae, dermis, and to a lesser extent in skeletal muscle, lung, and kidney.|||Increases the platelet count associated with splenomegaly. May have an important role in neuronal precursor development and maturation.|||Not detected in adult tissues.|||Secreted http://togogenome.org/gene/10090:Tnfrsf25 ^@ http://purl.uniprot.org/uniprot/B1AWN9|||http://purl.uniprot.org/uniprot/Q8VD70 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Trpv4 ^@ http://purl.uniprot.org/uniprot/Q9EPK8 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily.|||Cell membrane|||Detected in liver, kidney, heart, brain cortex, cerebellum and brainstem (at protein level). Expressed in salivary glands (at protein level) (PubMed:16571723). Expressed in heart, lung, spleen, liver, kidney, brain, skeletal muscle and testis. In the central nervous system, expressed in the lamina terminalis (arched vascular organ and neurons of the subfornical organ), median preoptic area, ventral hippocampal commissure, and ependymal cells of the choroid plexus. In the cochlea, expressed in both inner and outer hair cells, and in marginal cells of the cochlear stria vascularis. Expressed in large neurons of the trigeminal ganglion. In the kidney cortex, strongly expressed by epithelial cells of tubules and much weaker in glomeruli.|||Homotetramer. Interacts with calmodulin (By similarity). Interacts with CTNNB1 (PubMed:20413591). The TRPV4 and CTNNB1 complex can interact with CDH1 (PubMed:20413591). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 (By similarity). Interacts with MAP7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES (PubMed:14517216, PubMed:12538589). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) (PubMed:16627472, PubMed:18174177). Interacts with ITPR3 (By similarity). Interacts with AQP5; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (PubMed:16571723). Interacts with ANO1 (PubMed:24509911). Interacts (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040). Interacts with DDX3X; this interaction is decreased when the channel is activated (By similarity).|||Mice display impairment of the intercellular junction-dependent barrier function in the skin (PubMed:20413591). Increased energy expenditure and improved insulin sensitivity in white adipose tissues (PubMed:23021218). Reduced Ca2+ entry and loss of regulatory volume decrease in response to hypotonicity in acinar cells (PubMed:16571723).|||N-glycosylated.|||Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11094154). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:12093812, PubMed:14691263, PubMed:16368742, PubMed:16571723). Also activated by heat, low pH, citrate and phorbol esters (PubMed:14691263). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (By similarity). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (By similarity). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (PubMed:20413591). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (PubMed:23021218). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (PubMed:23021218). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (PubMed:16571723). Required for normal development and maintenance of bone and cartilage (By similarity). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (By similarity).|||The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding. The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides.|||adherens junction|||cilium http://togogenome.org/gene/10090:Fam3b ^@ http://purl.uniprot.org/uniprot/Q9D309 ^@ Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FAM3 family.|||By glucose.|||Expressed at high levels in the pancreas and, to a lesser extent, in small intestine and prostate. Also detected in stomach, testis and fetal liver. In the pancreas, localized in the islets of Langerhans; in the testis, found primarily in the round spermatids; in the CNS, found in the Purkinje cell layer of the cerebellum and in nerve cell bodies of numerous brainstem nuclei.|||Induces apoptosis of alpha and beta cells in a dose- and time-dependent manner.|||It is unclear whether the N-terminus residue of the mature protein is Glu-30 or Ser-46.|||O-glycosylated.|||Secreted http://togogenome.org/gene/10090:Mbd2 ^@ http://purl.uniprot.org/uniprot/Q9Z2E1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides (PubMed:9774669). Binds hemimethylated DNA as well (By similarity). Recruits histone deacetylases and DNA methyltransferases to chromatin (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (By similarity). Acts as transcriptional repressor and plays a role in gene silencing (By similarity). Functions as a scaffold protein, targeting GATAD2A and GATAD2B to chromatin to promote repression (By similarity). May enhance the activation of some unmethylated cAMP-responsive promoters (By similarity). Selectively represses transcription activity of methylated rRNA promoters (PubMed:14610093).|||Chromosome|||Heterodimer with MBD3 (via N-terminus) (By similarity). Component of the MeCP1 complex that contains HDAC1 and HDAC2 (By similarity). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (By similarity). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (By similarity). Interacts with CDK2AP1 (By similarity). Interacts with DHX9 (By similarity). Interacts with DNMT1 (By similarity). Interacts with GATAD2A/p66-alpha (By similarity). Interacts with GATAD2B/p66-beta (By similarity). Interacts with GPN1 (By similarity). Interacts with MIZF (By similarity). Interacts with PRMT5 (By similarity). Interacts with SIN3A (By similarity). Interacts with SPHK2 (By similarity).|||Highly expressed in brain, heart, kidney, lung, skeletal muscle, spleen and testis. Detected at lower levels in embryonic stem cells.|||Nucleus http://togogenome.org/gene/10090:Rgs13 ^@ http://purl.uniprot.org/uniprot/Q8K443 ^@ Function ^@ Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to both G(i)-alpha and G(q)-alpha. http://togogenome.org/gene/10090:Treml1 ^@ http://purl.uniprot.org/uniprot/Q8K558 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cell surface receptor that may play a role in the innate and adaptive immune response.|||Cytoplasm|||Highly expressed in bone marrow leukocytes, splenic megakaryocytes and platelets. Detected in brain, liver and in peritoneal monocytes.|||Phosphorylated on tyrosine residues.|||When phosphorylated, interacts with PTPN11 (By similarity). When phosphorylated, interacts with PTPN6. http://togogenome.org/gene/10090:Fgfbp3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0R6|||http://purl.uniprot.org/uniprot/Q1HCM0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibroblast growth factor-binding protein family.|||Expression is first detected at 10 dpc and reaches a peak at birth. After birth, levels decrease and remain constant throughout postnatal development.|||Heparin-binding protein which binds to FGF2, prevents binding of FGF2 to heparin and probably inhibits immobilization of FGF2 on extracellular matrix glycosaminoglycans, allowing its release and subsequent activation of FGFR signaling which leads to increased vascular permeability.|||In the adult, highly expressed in brain with lower levels in ovary. In the embryo, highest levels are found in the brain and spinal cord at 14 dpc and expression is almost completely restricted to the brain by 18 dpc. In the adult and postnatal brain, highly expressed in the orbitofrontal cortex where it is concentrated primarily in differentiated neurons.|||Interacts with FGF2.|||Mutants display a range of anxiety-related behaviors including reduced time spent in the central area of the open-field arena, reduced activity in lit areas of a light/dark transition test and prolonged latency to feeding in a novelty induced hypophagia test which assesses the drive to drink a sweetened milk solution.|||Secreted http://togogenome.org/gene/10090:Cpa1 ^@ http://purl.uniprot.org/uniprot/Q7TPZ8 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Tmem183a ^@ http://purl.uniprot.org/uniprot/Q9JJB9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM183 family.|||Membrane http://togogenome.org/gene/10090:Tspear ^@ http://purl.uniprot.org/uniprot/J3S6Y1 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell surface|||In the organ of Corti, expression at postnatal day 1 (P1) is restricted to the basal region of the stereocilia of inner and outer hair cells (at protein level). Expressed in the organ of Corti at P1 and P7, in cochlear ganglion, stria vascularis and vestibular ends at P7, and in inferior colliculus, remaining brainstem, cerebellum, brain hemispheres and retina at P1, P7 and in the adult. Also detected in adult liver, lung, kidney, intestine and testis but not in heart or skeletal muscle.|||Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway. May play a role in development or function of the auditory system.|||Secreted|||stereocilium http://togogenome.org/gene/10090:Dhdds ^@ http://purl.uniprot.org/uniprot/Q99KU1 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UPP synthase family.|||Binds 1 magnesium ion per subunit.|||Endoplasmic reticulum membrane|||Forms an active dehydrodolichyl diphosphate synthase complex with NUS1. Interacts with NPC2.|||The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs.|||With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length. Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol. http://togogenome.org/gene/10090:Zdhhc23 ^@ http://purl.uniprot.org/uniprot/B7ZNY8|||http://purl.uniprot.org/uniprot/Q5Y5T3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family.|||Expressed in the brain.|||Golgi apparatus membrane|||Interacts with NOS1.|||Membrane|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates and be involved in a variety of cellular processes. Palmitoyltransferase that mediates palmitoylation of KCNMA1, regulating localization of KCNMA1 to the plasma membrane. May be involved in NOS1 regulation and targeting to the synaptic membrane.|||The DHHC domain is required for palmitoyltransferase activity.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Cs ^@ http://purl.uniprot.org/uniprot/Q9CZU6 ^@ Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the citrate synthase family.|||Citrate synthase is found in nearly all cells capable of oxidative metabolism.|||Homodimer.|||Methylated. Trimethylation at Lys-395 by CSKMT decreases citrate synthase activity.|||Mitochondrion matrix http://togogenome.org/gene/10090:Slamf9 ^@ http://purl.uniprot.org/uniprot/Q9D780 ^@ Function|||Subcellular Location Annotation ^@ May play a role in the immune response.|||Membrane http://togogenome.org/gene/10090:Sycp3 ^@ http://purl.uniprot.org/uniprot/A2RSE7|||http://purl.uniprot.org/uniprot/P70281 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the XLR/SYCP3 family.|||Chromosome|||Component of the lateral elements of synaptonemal complexes (PubMed:16717126). Homotetramer; the tetrameric helix bundles assemble end to end into long homopolimeric fibers that exhibit a transversal striation with a periodicity of about 20 nm (in vitro) (By similarity). Interacts with SYCP2 (PubMed:16717126). Forms a complex with EWSR1, PRDM9, REC8 and SYCP1; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (PubMed:27932493).|||Component of the synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase (PubMed:11311943, PubMed:22761579). Required for centromere pairing during meiosis in male germ cells (PubMed:22761579). Required for normal meiosis during spermatogenesis and male fertility (PubMed:10678170). Plays a lesser role in female fertility (PubMed:10678170, PubMed:12004129). Required for efficient phosphorylation of HORMAD1 and HORMAD2 (PubMed:22346761).|||Composed of a long central coiled coil domain. The N-terminal and C-terminal regions interact with DNA.|||Detected in oocytes (PubMed:16717126). Detected in spermatocytes and testis (at protein level) (PubMed:10678170, PubMed:16717126, PubMed:22761579).|||Homozygous males with null mutations have smaller testes and are sterile, due to massive apoptotic cell death of male germ cells during meiotic prophase. Spermatocytes fail to form axial/lateral elements and synaptonemal complexes, and the chromosomes in the mutant spermatocytes do not synapse (PubMed:10678170). In contrast, females are fertile and generate healthy offspring. However, they exhibit a sharp reduction in litter size that increases with advancing maternal age (PubMed:10678170, PubMed:12004129). In contrast to wild-type, a high percentage of the mutant embryos display aneuploidy (PubMed:12004129).|||Nucleus|||Phosphorylated.|||centromere http://togogenome.org/gene/10090:Cd46 ^@ http://purl.uniprot.org/uniprot/O88174 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with C3b. Interacts with C4b. Interacts with moesin/MSN.|||Lacks transmembrane domain, probably secreted.|||May be O-glycosylated.|||May be involved in the fusion of the spermatozoa with the oocyte during fertilization.|||Mice have normal testis and fertile sperm.|||N-glycosylated.|||Not expressed until 29 dpc. Expressed in parallel with synthesis of spermatids.|||Present only in testis (at protein level).|||Secreted|||acrosome inner membrane http://togogenome.org/gene/10090:Bpnt2 ^@ http://purl.uniprot.org/uniprot/Q80V26 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ At 18.5 dpc, widely expressed with enhanced levels in brain, spinal cord, lung and kidney, including medulla and cortex. In the developing brain, strongly expressed in the neopallial cortex and throughout the cerebellum with intense expression within the developing Purkinje cells and adjacent choroid plexus. Strong expression also observed within the pons and throughout the medulla oblongata. In the lung, expressed in individual pneumocytes and particularly in cells surrounding developing bronchi/bronchioles. Moderate expression in chondrocytes of costal cartilage and in the surrounding perichondrium.|||Belongs to the inositol monophosphatase superfamily.|||Exhibits 3'-nucleotidase activity toward adenosine 3',5'-bisphosphate (PAP), namely hydrolyzes adenosine 3',5'-bisphosphate into adenosine 5'-monophosphate (AMP) and a phosphate (PubMed:18695242). May play a role in the formation of skeletal elements derived through endochondral ossification, possibly by clearing adenosine 3',5'-bisphosphate produced by Golgi sulfotransferases during glycosaminoglycan sulfation (PubMed:18695242). Has no activity toward 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or inositol phosphate (IP) substrates including I(1)P, I(1,4)P2, I(1,3,4)P3, I(1,4,5)P3 and I(1,3,4,5)P4.|||Golgi apparatus|||Mutant animals experience severe respiratory distress and died within minutes after birth. At 18.5 dpc, lungs exhibit small alveolar spaces and thickened septa. The rib cage cartilage is hypocellular with abnormal, fibrous-appearing extracellular matrix. Animals show severe skeletal abnormalities, most notably in the longitudinal growth of bones formed by endochondral ossification. The length of the axial skeleton is reduced. The appendicular bones of the upper limbs, as well as the ilium, femur, tibia and fibula of the lower limbs are markedly shorter than in wild-type littermates. The rib cages display malformation characterized by reduced sternal length and correspondingly diminished rib spacing. The process of intramembranous ossification is normal. Mutant animals exhibit a deficiency in glycosaminoglycan sulfation. Mutant cartilage and lung exhibit a substantial decrease in chondroitin 4-sulfate and an increase in nonsulfated chondroitin compared with wild type tissue.|||N-glycosylated (By similarity). Contains N-linked glycan resistant to endoglycosydase H (By similarity).|||Strongly inhibited by lithium.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Tap2 ^@ http://purl.uniprot.org/uniprot/P36371|||http://purl.uniprot.org/uniprot/Q792S7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ABC transporter associated with antigen processing. In complex with TAP1 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. During the transport cycle alternates between 'inward-facing' state with peptide binding site facing the cytosol to 'outward-facing' state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent 'outward-facing' conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the 'inward facing' state for a new cycle. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.|||Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.|||Endoplasmic reticulum membrane|||Heterodimer of TAP1 and TAP2 (TAP1-TAP2). A component of the peptide loading complex (PLC), interacts via TAPBP with MHCI heterodimer; this interaction mediates peptide-MHCI assembly.|||Membrane|||The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis.|||The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2. http://togogenome.org/gene/10090:Krt72 ^@ http://purl.uniprot.org/uniprot/Q6IME9 ^@ Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (By similarity).|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:F13b ^@ http://purl.uniprot.org/uniprot/Q07968|||http://purl.uniprot.org/uniprot/Q3UER0 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Lacks conserved residue(s) required for the propagation of feature annotation.|||Predominantly expressed in liver and kidney.|||Secreted|||Tetramer of two A chains (F13A1) and two B (F13B) chains.|||The B chain of factor XIII is not catalytically active, but is thought to stabilize the A subunits and regulate the rate of transglutaminase formation by thrombin. http://togogenome.org/gene/10090:Igf2r ^@ http://purl.uniprot.org/uniprot/Q07113|||http://purl.uniprot.org/uniprot/Q8C6V9 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MRL1/IGF2R family.|||Binds HA-I and HA-II plasma membrane adapters (By similarity). Interacts with DPP4; the interaction is direct. Binds GGA1, GGA2 and GGA3 (By similarity). Interacts with the heterotrimeric retromer cargo-selective complex (CSC), formed by VPS26 (VPS26A or VPS26B), VPS29 and VPS35; which is involved in retrograde trafficking of the receptor from endosomes to the Golgi apparatus (By similarity).|||Contains 15 repeating units of approximately 147 AA harboring four disulfide bonds each. The most highly conserved region within the repeat consists of a stretch of 13 AA that contains cysteines at both ends.|||Endosome membrane|||Golgi apparatus membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex. The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer. This receptor also binds IGF2. Acts as a positive regulator of T-cell coactivation by binding DPP4.|||Palmitoylated. Undergoes cysteine S-palmitoylation which promotes interaction with the retromer cargo-selective complex which mediates its retrograde trafficking to the Golgi apparatus. http://togogenome.org/gene/10090:Gm21344 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or11q2 ^@ http://purl.uniprot.org/uniprot/A2AHM8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defb3 ^@ http://purl.uniprot.org/uniprot/Q9WTL0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Antimicrobial activity against Gram-negative bacteria E.coli and P.aeruginosa.|||Belongs to the beta-defensin family. LAP/TAP subfamily.|||By bacterial infection.|||Highest expression in salivary glands, epididymis, ovary and pancreas and to a lesser extent in lung, liver and brain. Low or no expression in skeletal muscle and tongue.|||Secreted http://togogenome.org/gene/10090:Slc12a8 ^@ http://purl.uniprot.org/uniprot/Q8VI23 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the SLC12A transporter family.|||Cation/chloride cotransporter that may play a role in the control of keratinocyte proliferation.|||Membrane http://togogenome.org/gene/10090:Rap1a ^@ http://purl.uniprot.org/uniprot/P62835 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by guanine nucleotide-exchange factors (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR.|||Belongs to the small GTPase superfamily. Ras family.|||Cell junction|||Cell membrane|||Cytoplasm|||Early endosome|||Expressed in the testis and sperm midpiece (at protein level).|||Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (active GTP-bound form preferentially) with KRIT1 (via C-terminus FERM domain); the interaction does not induce the opening conformation of KRIT1. In its GTP-bound form interacts with PLCE1 and RADIL. Interacts with SGSM1, SGSM2 and SGSM3. Interacts (via GTP-bound active form) with RAPGEF2 (via Ras-associating domain) (By similarity). Interacts with TBC1D21 (PubMed:30360518). Interacts with RAP1GDS1 (By similarity).|||Induces morphological reversion of a cell line transformed by a Ras oncogene. Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner. Together with ITGB1BP1, regulates KRIT1 localization to microtubules and membranes (By similarity). Plays a role in nerve growth factor (NGF)-induced neurite outgrowth. Plays a role in the regulation of embryonic blood vessel formation. Involved in the establishment of basal endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR expression at endothelial cell-cell junctions.|||Late endosome|||perinuclear region http://togogenome.org/gene/10090:Rnase9 ^@ http://purl.uniprot.org/uniprot/P60154|||http://purl.uniprot.org/uniprot/Q5QJV3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pancreatic ribonuclease family.|||Does not exhibit any ribonuclease activity.|||Secreted http://togogenome.org/gene/10090:Egln1 ^@ http://purl.uniprot.org/uniprot/Q91YE3 ^@ Cofactor|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Fe(2+) ion per subunit.|||Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.|||Cytoplasm|||Expressed in heart, brain liver, skeletal muscle and kidney. Low levels were detected in the lung. Constitutively expressed during differentiation of C2C12 skeletal myocytes.|||Induced by growth factors in cultured vascular smooth muscle. Up-regulated in proliferating myoblasts induced to form differentiated myotubes.|||Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EPAS1. Interacts with CBFA2T3 and HIF1A.|||Nucleus|||Null mice are smaller than wild type and are erythematous with some animals having evidence of retroperitoneal hemorrhage. The resulting polycythemia can cause thrombosis and cardiac failure and animals die off after 10 weeks. Erythropoietin levels are increased in kidneys but not in livers. In neonatal null mice exposed to 75% oxygen, there are high levels of HIF1A nuclear abundance in retinal tissues accompanied by well-preserved retinal microvessels compared to wild type where oxygen-treated retinas exhibit reverse effects with increased risks of retinopathy.|||S-nitrosylation inhibits the enzyme activity up to 60% under aerobic conditions. Chelation of Fe(2+) has no effect on the S-nitrosylation. It is uncertain whether nitrosylation occurs on Cys-300 or Cys-303.|||The beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity. http://togogenome.org/gene/10090:Oxt ^@ http://purl.uniprot.org/uniprot/P35454|||http://purl.uniprot.org/uniprot/Q545V4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the vasopressin/oxytocin family.|||Interacts with oxytocin receptor (Ki=1.5 nM) (By similarity). Interacts with vasopressin V1aR/AVPR1A (Ki=37 nM), V1bR/AVPR1B (Ki=222 nM), and V2R/AVPR2 receptors (Ki=823 nM) (By similarity).|||Neurophysin 1 specifically binds oxytocin.|||Oxytocin causes contraction of the smooth muscle of the uterus and of the mammary gland. Acts by binding to oxytocin receptor (OXTR) (By similarity). http://togogenome.org/gene/10090:Tsc22d3 ^@ http://purl.uniprot.org/uniprot/Q9Z2S7 ^@ Developmental Stage|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TSC-22/Dip/Bun family.|||Can form homodimers, however it is likely to function as a monomer (PubMed:11397794). Interacts with NFKB1 (By similarity). Interacts (via N-terminus) with JUN and FOS; these interactions inhibit the binding of active AP1 to its target DNA (PubMed:11397794).|||Cytoplasm|||Expressed in T-cells (PubMed:26752201). Expression inversely correlates with T-cell activation, being higher in resting cells and lower in cells activated by TCR/CD3 triggering (at protein level) (PubMed:11468175). Constitutively expressed in lung, intestine, kidney and liver, most probably by resident cells from the macrophage lineage (PubMed:12393603). Expressed in thymus, lymph nodes, bone marrow, spleen, lung and skeletal muscle (PubMed:9430225).|||Expressed in differentiating myoblasts at a time of myotube formation.|||Expressed in spleen and skeletal muscle (at protein level) (PubMed:20124407). Expressed in the cortex, medulla and papilla of the kidney (PubMed:17147695).|||Expressed in spleen and skeletal muscle (at protein level).|||Expressed in the cortex, medulla and papilla of the kidney.|||Induced by aldosterone.|||Induced by dexamethasone in lymphoid cells (PubMed:9430225, PubMed:12393603). Induced by Il4, Il10 and Il13 expression in monocyte/macrophage cells (PubMed:12393603). Transiently induced by Il2 deprivation in T-cells.|||Induced by renal hyperosmotic stress and aldosterone (PubMed:17147695). Induced by the synthetic glucocorticoid dexamethasone in differentiating myoblasts (PubMed:20124407).|||Induced by the synthetic glucocorticoid dexamethasone in differentiating myoblasts.|||Inhibits myogenic differentiation and mediates anti-myogenic effects of glucocorticoids by binding and regulating MYOD1 and HDAC1 transcriptional activity resulting in reduced expression of MYOG.|||Interacts with MYOD1 (PubMed:20124407). Interacts with HDAC1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity (PubMed:20124407).|||Interacts with MYOD1.|||Nucleus|||Protects T-cells from IL2 deprivation-induced apoptosis through the inhibition of FOXO3A transcriptional activity that leads to the down-regulation of the pro-apoptotic factor BCL2L11 (PubMed:26752201). In macrophages, plays a role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL10 (By similarity). In T-cells, inhibits anti-CD3-induced NFKB1 nuclear translocation and thereby NFKB1 DNA-binding activities (By similarity). In vitro, suppresses AP-1 transcription factor complex DNA-binding activities (PubMed:11397794).|||The leucine-zipper is involved in homodimerization. http://togogenome.org/gene/10090:Rcan2 ^@ http://purl.uniprot.org/uniprot/Q543P2|||http://purl.uniprot.org/uniprot/Q8VIP4|||http://purl.uniprot.org/uniprot/Q9JHG2 ^@ Function|||Similarity|||Tissue Specificity ^@ Belongs to the RCAN family.|||Highest expression in heart, skeletal muscle and brain. Lower expression in all other tissues.|||Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development. http://togogenome.org/gene/10090:Phf13 ^@ http://purl.uniprot.org/uniprot/Q8K2W6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with histone H3 that is trimethylated at 'Lys-4' (H3K4me3). Interacts with GSK3B (By similarity).|||Modulates chromatin structure. Required for normal chromosome condensation during the early stages of mitosis. Required for normal chromosome separation during mitosis (By similarity).|||Nucleus|||Subject to proteasomal degradation. Stable when bound to chromatin. The soluble form is rapidly degraded (By similarity).|||nucleoplasm http://togogenome.org/gene/10090:Tut4 ^@ http://purl.uniprot.org/uniprot/A2A8R7|||http://purl.uniprot.org/uniprot/B2RX14|||http://purl.uniprot.org/uniprot/Q3V3D5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DNA polymerase type-B-like family.|||Cytoplasm|||Cytoplasmic ribonucleoprotein granule|||Double conditional knockouts that have deleted both TUT4 and TUT7 at the secondary oocyte stage are infertile. Females ovulate normal numbers of oocytes with normal morphology of antral follicles but with a slight decrease in the frequency of surrounded nucleolus state oocytes. Mutant oocytes are unable to support early embryonic development, they fail to complete meiosis I properly.|||Interacts with LIN28A in the presence of pre-let-7 RNA (PubMed:28671666). Interacts with T2BP. Interacts with MOV10; the interaction is RNA-dependent.|||Nucleus|||Ubiquitously expressed.|||Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:28792939). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (PubMed:28792939). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesiS using 3 different uridylation mechanisms (By similarity). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:28671666). Add oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (By similarity). May also suppress Toll-like receptor-induced NF-kappa-B activation via binding to T2BP (By similarity). Does not play a role in replication-dependent histone mRNA degradation (By similarity). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:28671666, PubMed:28792939, PubMed:22898984). TUT4 and TUT7 restrict retrotransposition of long interspersed element-1 (LINE-1) in cooperation with MOV10 counteracting the RNA chaperonne activity of L1RE1. TUT7 uridylates LINE-1 mRNAs in the cytoplasm which inhibits initiation of reverse transcription once in the nucleus, whereas uridylation by TUT4 destabilizes mRNAs in cytoplasmic ribonucleoprotein granules (By similarity).|||Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activities while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation. http://togogenome.org/gene/10090:Twist1 ^@ http://purl.uniprot.org/uniprot/P26687 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of pro-inflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation. Represses the activity of the circadian transcriptional activator: NPAS2-BMAL1 heterodimer.|||By TNF-alpha.|||Efficient DNA binding requires dimerization with another bHLH protein (PubMed:16502419, PubMed:17893140). Homodimer or heterodimer with E proteins such as TCF3 (PubMed:16502419, PubMed:17893140, PubMed:23395635). ID1 binds preferentially to TCF3 but does not interact efficiently with TWIST1 so ID1 levels control the amount of TCF3 available to dimerize with TWIST1 and thus determine the type of dimer formed (PubMed:16502419, PubMed:17893140).|||Nucleus|||Subset of mesodermal cells. http://togogenome.org/gene/10090:Lcn12 ^@ http://purl.uniprot.org/uniprot/Q2TA58|||http://purl.uniprot.org/uniprot/Q6JVL5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Binds all-trans retinoic acid and may act as a retinoid carrier protein within the epididymis. May play a role in male fertility (By similarity).|||Expressed in epididymis.|||Monomer.|||Secreted http://togogenome.org/gene/10090:Prl8a6 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0X0|||http://purl.uniprot.org/uniprot/Q9DAY2 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed specifically in the spongiotrophoblast and trophoblast giant cells from the junctional zone of the chorioallantoic placenta.|||Expression increased from midgestation to the end of the pregnancy.|||Secreted http://togogenome.org/gene/10090:Inpp4a ^@ http://purl.uniprot.org/uniprot/D3YUD3|||http://purl.uniprot.org/uniprot/D3Z230|||http://purl.uniprot.org/uniprot/E9Q9A0|||http://purl.uniprot.org/uniprot/F6V2U0|||http://purl.uniprot.org/uniprot/Q3UEQ1|||http://purl.uniprot.org/uniprot/Q9EPW0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.|||Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate (PubMed:20463662). Catalyzes also inositol 1,3,4-trisphosphate and inositol 1,4-bisphosphate (By similarity). Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival (PubMed:11087841, PubMed:19325558). May protect neurons from excitotoxic cell death by regulating the synaptic localization of cell surface N-methyl-D-aspartate-type glutamate receptors (NMDARs) and NMDAR-mediated excitatory postsynaptic current (PubMed:20463662).|||Cell membrane|||Cytoplasm|||Deficient mice are born at the expected Mendelian ratio and are indistinguishable from wild-type at birth. However, at about 14 days after birth, the growth rate of the mice slow significantly and all mutants died by the fourth week. At about 12 days after birth mice are unable to walk. In addition mice show extensive neurodegeneration accompanied by involuntary movements atarting at about 14 days after birth.|||Early endosome membrane|||Interacts with INPP5F.|||Nucleus|||Postsynaptic density|||Recycling endosome membrane|||Spleen, skeletal muscle, lung and uterus. http://togogenome.org/gene/10090:Spin2e ^@ http://purl.uniprot.org/uniprot/A0A571BDE3 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Mier2 ^@ http://purl.uniprot.org/uniprot/Q3U3N0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Nucleus|||Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2.|||Transcriptional repressor. http://togogenome.org/gene/10090:Bex6 ^@ http://purl.uniprot.org/uniprot/Q3TZW7 ^@ Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BEX family.|||Cytoplasm|||The human orthologous protein seems not to exist.|||Ubiquitinated (PubMed:15958283). Degraded by the proteasome (PubMed:15958283). http://togogenome.org/gene/10090:Tnni3 ^@ http://purl.uniprot.org/uniprot/P48787|||http://purl.uniprot.org/uniprot/Q497F1 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the troponin I family.|||Interacts with TRIM63 (By similarity). Binds to actin and tropomyosin. Interacts with STK4/MST1 (By similarity).|||Phosphorylated at Ser-23 and Ser-24 by PRKD1; phosphorylation reduces myofilament calcium sensitivity. Phosphorylated preferentially at Thr-32. Phosphorylation by STK4/MST1 alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T) (By similarity). Phosphorylated at Ser-43 and Ser-45 by PRKCE; phosphorylation increases myocardium contractile dysfunction.|||Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. http://togogenome.org/gene/10090:C1qb ^@ http://purl.uniprot.org/uniprot/P14106 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ C1 is a calcium-dependent trimolecular complex of C1q, R and S in the molar ration of 1:2:2. C1q subcomponent is composed of nine subunits, six of which are disulfide-linked dimers of the A and B chains, and three of which are disulfide-linked dimers of the C chain.|||C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.|||Highest expression in thioglycolate-activated peritoneal macrophages. Also found in spleen, thymus and heart. Very weak expression liver, kidney, lung and intestine.|||Hydroxylated on lysine and proline residues. Hydroxylated lysine residues can be glycosylated. Mouse C1Q contains up to 64.0 hydroxylysine-galactosylglucose residues. Total percentage hydroxylysine residues glycosylated is 95.1%. Contains no hydroxylysine-monosaccharides.|||Secreted http://togogenome.org/gene/10090:Vmn1r224 ^@ http://purl.uniprot.org/uniprot/E9PWK2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tlr9 ^@ http://purl.uniprot.org/uniprot/Q9EQU3 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain (PubMed:18931679, PubMed:18820679). Cleavage requires UNC93B1 (PubMed:18820679). Proteolytically processed by first removing the majority of the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling (PubMed:21402738).|||Belongs to the Toll-like receptor family.|||Endoplasmic reticulum membrane|||Endosome|||Expressed in the basolateral region of gastric epithelial cells with high levels detected in antrum and body mucosa (at protein level). Detected in spleen and stomach at higher levels in C57BL/6 mice than BALB/C.|||Following Helicobacter infection, down-regulated in C57BL/6 mice and up-regulated in BALB/C mice.|||Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:18931679, PubMed:21402738, PubMed:14993594, PubMed:17474149, PubMed:25686612, PubMed:18820679). Plays a role in defense against systemic mouse cytomegalovirus infection (PubMed:14993594). Controls lymphocyte response to Helicobacter infection (PubMed:17474149). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity).|||Lysosome|||Monomer and homodimer. Exists as a monomer in the absence of unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic processing of an insertion loop (Z-loop) is required for homodimerization upon binding to the unmethylated CpG ligand leading to its activation (By similarity). Interacts with MYD88 via their respective TIR domains (PubMed:18820679). Interacts with BTK (By similarity). Interacts (via transmembrane domain) with UNC93B1 (PubMed:17452530, PubMed:18931679). Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (PubMed:21940676). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800). Interacts with SMPDL3B (PubMed:26095358).|||Reduced proliferation of lymphocytes, reduced interferon-gamma production by splenocytes and reduced neutrophil numbers following Helicobacter infection.|||phagosome http://togogenome.org/gene/10090:Cyp4f15 ^@ http://purl.uniprot.org/uniprot/Q8VCA4|||http://purl.uniprot.org/uniprot/Q99N18 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Pcbd1 ^@ http://purl.uniprot.org/uniprot/P61458 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pterin-4-alpha-carbinolamine dehydratase family.|||Cytoplasm|||Homotetramer and homodimer. Heterotetramer with HNF1A; formed by a dimer of dimers (By similarity). Interacts with HNF1B (via HNF-p1 domain); the interaction increases HNF1B transactivation activity (By similarity).|||Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity (By similarity). Also acts as a coactivator for HNF1B-dependent transcription (By similarity).|||Mainly expressed in the liver, in pancreatic cells, and in the kidney, especially in the distal convoluted tubule, in the cortical thick ascending limb of Henle's loop and in the connecting tubule.|||Nucleus|||Up-regulated by a low magnesium-containing diet. http://togogenome.org/gene/10090:Cpne8 ^@ http://purl.uniprot.org/uniprot/Q9DC53 ^@ Caution|||Cofactor|||Function|||Similarity ^@ Belongs to the copine family.|||Binds 3 Ca(2+) ions per C2 domain.|||It is uncertain whether Met-1 or Met-14 is the initiator.|||Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes. http://togogenome.org/gene/10090:Spata31d1b ^@ http://purl.uniprot.org/uniprot/E9QA57 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SPATA31 family.|||Membrane http://togogenome.org/gene/10090:Nfkbib ^@ http://purl.uniprot.org/uniprot/Q60778 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NF-kappa-B inhibitor family.|||Cytoplasm|||Highly expressed in testis followed by spleen.|||Inhibits NF-kappa-B by complexing with and trapping it in the cytoplasm. However, the unphosphorylated form resynthesized after cell stimulation is able to bind NF-kappa-B allowing its transport to the nucleus and protecting it to further NFKBIA-dependent inactivation. Association with inhibitor kappa B-interacting NKIRAS1 and NKIRAS2 prevent its phosphorylation rendering it more resistant to degradation, explaining its slower degradation.|||Interacts with THRB (via ligand-binding domain) (By similarity). Interacts with RELA and REL (PubMed:8816457). Interacts with COMMD1 (By similarity). Interacts with inhibitor kappa B-interacting Ras-like NKIRAS1 and NKIRAS2 (PubMed:10657303).|||Nucleus|||Phosphorylated by RPS6KA1; followed by degradation. Interaction with NKIRAS1 and NKIRAS2 probably prevents phosphorylation. http://togogenome.org/gene/10090:Mafb ^@ http://purl.uniprot.org/uniprot/P54841 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional activator or repressor. Plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, osteoclast, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Required for the transcriptional activation of HOXB3 in the rhombomere r5 in the hindbrain (PubMed:11823429).|||Belongs to the bZIP family. Maf subfamily.|||Expressed in pancreatic alpha-cells (glucagon-positive cells), in podocytes of the kidney and macrophages (at protein level). Most abundant in kidney, gut, lung and brain.|||Expressed in pancreatic alpha-cells at 10.5 dpc (PubMed:17901057). Expressed in insulin and glucagon islet progenitor cells at 12 dpc onwards (at protein level) (PubMed:16443760). Detectable at 8.0 dpc (one somite) as a band in the caudal hindbrain and by 8.5 dpc (six to eight somites) as a sharp rostral edge coincident with the rhombomeres (r) 4 and 5 boundary and a diffuse caudal edge located midway through r6 (PubMed:8001130). Expressed in the lens epithelial cells at 10.5 to 14.5 dpc (PubMed:10383433). Expressed in the cochlear nucleus at 15.5 dpc (PubMed:17977745).|||Homodimer or heterodimer with other bHLH-Zip transcription factors. Forms homodimers and heterodimers with FOS, FOSB and FOSL2, but not with JUN proteins (JUN, JUNB and JUND). Interacts with the intracellular cytoplasmic domain of LRP1 (LRPICD); the interaction results in a moderate reduction of MAFB transcriptional potential (By similarity). Binds DNA as a homodimer or a heterodimer. Interacts with PAX6; the interaction is direct. Interacts with ETS1 and LRP1.|||Mice show a defect in frequency of respiratory rhythm with a fatal apnea at birth due to lack of neurons from the preBoetC region. They displayed renal dysgenesis with abnormal podocyte differentiation as well as tubular apoptosis. They show altered actin-dependent macrophage morphology. They show a reduced number of cells expressing insulin and glucagon. Embryos also lack the abducens nerve which normaly innervates the lateral rectus muscle that is involved in eye movement (PubMed:27181683).|||Nucleus|||Sumoylated. Sumoylation on Lys-32 and Lys-297 stimulates its transcriptional repression activity and promotes macrophage differentiation from myeloid progenitors.|||The leucine-zipper domain is involved in the interaction with LRPICD. http://togogenome.org/gene/10090:Vps41 ^@ http://purl.uniprot.org/uniprot/Q5KU39 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS41 family.|||Component of the putative homotypic fusion and vacuole protein sorting (HOPS) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS39 and VPS41. Interacts with RILP, MON1B. Interacts with ARL8B (GTP-bound form); involved in recruitment to lysosomes and probably hierarchial assembly of the HOPS complex at lysosomal membranes. In vitro can self-assemble into a lattice. Associates with adapter protein complex 3 (AP-3) and clathrin:AP-3 complexes. Interacts with STX17; this interaction is increased in the absence of TMEM39A. Interacts with ARL8B and PLEKHM1; the interaction mediates the recruitment of the HOPS complex to lysosomes.|||Early endosome membrane|||Endosome membrane|||Late endosome membrane|||Lysosome membrane|||Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act in part as a core component of the putative HOPS endosomal tethering complex is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes implicated in degradation of endocytosed cargo. Required for fusion of autophagosomes with lysosomes. Links the HOPS complex to endosomal via its association with RILP and to lysosomal membranes via its association with ARL8B, suggesting that these interactions may bring the compartments to close proximity for fusion (By similarity). Involved in the direct trans-Golgi network to late endosomes transport of lysosomal membrane proteins independently of HOPS (By similarity). Involved in sorting to the regulated secretory pathway presumably implicating the AP-3 adapter complex (By similarity). May play a role in HOPS-independent function in the regulated secretory pathway (By similarity).|||clathrin-coated vesicle|||cytosol|||trans-Golgi network http://togogenome.org/gene/10090:Samd8 ^@ http://purl.uniprot.org/uniprot/Q14AQ4|||http://purl.uniprot.org/uniprot/Q9DA37 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sphingomyelin synthase family.|||Endoplasmic reticulum membrane|||It is uncertain whether Met-1 or Met-64 is the initiator.|||Membrane|||The SAM domain is required to retain SMAD8 in the endoplasmic reticulum. membrane protein (By similarity).|||sphingomyelin synthases synthesize sphingolipids through transfer of a phosphatidyl head group on to the primary hydroxyl of ceramide. SAMD8 is an endoplasmic reticulum (ER) transferase that has no sphingomyelin synthase activity but can convert phosphatidylethanolamine (PE) and ceramide to ceramide phosphatidylethanolamine (CPE) albeit with low product yield. Appears to operate as a ceramide sensor to control ceramide homeostasis in the endoplasmic reticulum rather than a converter of ceramides. Seems to be critical for the integrity of the early secretory pathway (By similarity). http://togogenome.org/gene/10090:Acat3 ^@ http://purl.uniprot.org/uniprot/Q80X81 ^@ Similarity ^@ Belongs to the thiolase-like superfamily. Thiolase family. http://togogenome.org/gene/10090:Rala ^@ http://purl.uniprot.org/uniprot/P63321 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).|||Belongs to the small GTPase superfamily. Ras family.|||Cell membrane|||Cleavage furrow|||Interacts (via effector domain) with RALBP1; during mitosis, recruits RALBP1 to the mitochondrion where it promotes DNM1L phosphorylation and mitochondrial fission (By similarity). Interacts with EXOC2/Sec5 and EXOC8/Exo84; binding to EXOC2 and EXOC8 is mutually exclusive. Interacts with Clostridium exoenzyme C3. Interacts with RALGPS1. Interacts with LPAR1 and LPAR2. Interacts with GRK2 in response to LPAR1 activation. RALA and GRK2 binding to LPAR1 is mutually exclusive (By similarity). Interacts with CDC42 (By similarity).|||Midbody ring|||Mitochondrion|||Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells (By similarity). The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling (PubMed:20005108). During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody (By similarity). During mitosis, also controls mitochondrial fission by recruiting to the mitochondrion RALBP1, which mediates the phosphorylation and activation of DNM1L by the mitotic kinase cyclin B-CDK1 (By similarity).|||Phosphorylated. Phosphorylation at Ser-194 by AURKA/Aurora kinase A, during mitosis, induces RALA localization to the mitochondrion where it regulates mitochondrial fission.|||Prenylation is essential for membrane localization. http://togogenome.org/gene/10090:Vezt ^@ http://purl.uniprot.org/uniprot/D3Z4E6|||http://purl.uniprot.org/uniprot/Q3ZK22 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the vezatin family.|||Cell membrane|||Embryos die at the time of implantation because of a defect in intercellular adhesion.|||Expressed in developing cochlear hair cells (PubMed:17567809). Isoform 1, isoform 2 and isoform 3 are expressed in testis. In the seminiferous epithelium, present exclusively in the acrosome of spermatids (at protein level).|||Interacts with USH2A (via the cytoplasmic region); the interaction associates VEZT with the USH2 complex at the stereocilia base (PubMed:17567809). Interacts with myosin MYO7A and the cadherin-catenins complex (By similarity).|||Membrane|||Nucleus|||Plays a pivotal role in the establishment of adherens junctions and their maintenance in adult life. Required for morphogenesis of the preimplantation embryo, and for the implantation process.|||Present in oocytes and at every embryonic stage (at protein level).|||acrosome|||adherens junction|||stereocilium membrane http://togogenome.org/gene/10090:Oxsr1 ^@ http://purl.uniprot.org/uniprot/Q6P9R2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated following phosphorylation at Thr-185 by WNK kinases (WNK1, WNK2, WNK3 or WNK4).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:17488636, PubMed:19633012, PubMed:21486947). Specifically recognizes and binds proteins with a RFXV motif (By similarity). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:12386165, PubMed:16382158, PubMed:17488636, PubMed:19633012, PubMed:21486947). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:16382158, PubMed:21972418). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16382158). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:17488636, PubMed:19633012). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (PubMed:21972418). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (By similarity). Phosphorylates RELL1, RELL2, RELT and PAK1 (By similarity). Phosphorylates PLSCR1 in the presence of RELT (By similarity).|||Embryonic lethality caused by angiogenesis and cardiac defects beginning at 10.5 dpc (PubMed:23386621). Conditional deletion in endothelial cells leads to cardiovascular developmental defects, leading to embryonic lethality (PubMed:23386621).|||Phosphorylation at Thr-185 by WNK kinases (WNK1, WNK2, WNK3 or WNK4) is required for activation (PubMed:21486947). Autophosphorylated; promoting its activity (By similarity).|||Ubiquitously expressed in all tissues examined, except thymus. http://togogenome.org/gene/10090:Fancf ^@ http://purl.uniprot.org/uniprot/E9Q5Z5 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. In complex with FANCA, FANCG and FANCL, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins.|||DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.|||Nucleus|||Viable with no gross developmental abnormalities or significant growth retardation. Gonad defects are present in both male and female mice. Testes are devoid of germ cells. Ovaries show premature depletion of primordial follicles with almost complete loss by 14 weeks of age, and aberrant estrous cycle. Significantly increased incidence of tumors, particularly ovarian tumors. http://togogenome.org/gene/10090:Ing3 ^@ http://purl.uniprot.org/uniprot/D3YUP8|||http://purl.uniprot.org/uniprot/Q8VEK6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ING family.|||Component of an histone acetyltransferase complex.|||Component of an histone acetyltransferase complex. Interacts with H3K4me3 and to a lesser extent with H3K4me2.|||Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (By similarity).|||Interacts with H3K4me3 and to a lesser extent with H3K4me2 (By similarity). Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC. HTATTIP/TIP60, EPC1, and ING3 together constitute a minimal HAT complex termed Piccolo NuA4. Component of a SWR1-like complex (By similarity).|||Nucleus|||The PHD-type zinc finger mediates the binding to H3K4me3. http://togogenome.org/gene/10090:Rnft2 ^@ http://purl.uniprot.org/uniprot/Q3UF64 ^@ Function|||Induction|||Subcellular Location Annotation ^@ E3 ubiquitin-protein ligase that negatively regulates IL3-dependent cellular responses through IL3RA ubiquitination and degradation by the proteasome, having an anti-inflammatory effect.|||Expression is induced by IL3 and inhibited by LPS.|||Membrane http://togogenome.org/gene/10090:Ldlrad3 ^@ http://purl.uniprot.org/uniprot/A2AR95|||http://purl.uniprot.org/uniprot/B2RR20|||http://purl.uniprot.org/uniprot/B7ZND2 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LDLR family.|||Cell membrane|||Expressed in the cerebral cortex and hippocampus.|||Interacts with APP precursor C-terminus (PubMed:21795536). Interacts directly with ITCH; this interaction promotes ITCH auto-ubiquitination leading to its degradation. Interacts directly with NEDD4; this interaction promotes NEDD4 auto-ubiquitination. Interacts directly with NEDD4L (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May influence APP processing, resulting in a decrease in sAPP-alpha production and increased amyloidogenic P3 peptide production (PubMed:21795536). May regulate ITCH and NEDD4 E3 ligase activity and degradation (By similarity). http://togogenome.org/gene/10090:Gm20809 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Gorasp1 ^@ http://purl.uniprot.org/uniprot/Q3TCN5|||http://purl.uniprot.org/uniprot/Q91X51 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GORASP family.|||Homodimer. Forms higher-order oligomers under interphase but not mitotic conditions. Dimers of the protein on one membrane might be able to interact with dimers on another and so stack cisternae. Interacts with the C-terminus of GOLGA2/GM130 under both mitotic and non-mitotic conditions. The interaction is critical for the correct targeting of both proteins to the cis-Golgi. Interacts with TMED2 and TMED3.|||Key structural protein of the Golgi apparatus (PubMed:32573693). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon (PubMed:32573693). Acting in concert with GORASP2/GRASP55, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks (PubMed:32573693). However, other studies suggest that GORASP1 plays an important role in assembly and membrane stacking of the cisternae, and in the reassembly of Golgi stacks after breakdown during mitosis (By similarity). Caspase-mediated cleavage of GORASP1 is required for fragmentation of the Golgi during apoptosis (By similarity). Also mediates, via its interaction with GOLGA2/GM130, the docking of transport vesicles with the Golgi membranes (By similarity). Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (By similarity).|||Myristoylated.|||No visible loss of Golgi stacking in intestinal tissue at postnatal day 10, 21 or 42, in combination with conditional knockout of GORASP2/GRASP55 (PubMed:32573693). However, cisternal cross-sectional diameters are reduced and rims of the Golgi cisternae are vacuolated (PubMed:32573693). Abolishes expression of GOLGA2/GM130 in the cisternae (PubMed:32573693).|||Phosphorylated by CDC2/B1 and PLK kinases during mitosis. Phosphorylation cycle correlates with the cisternal stacking cycle. Phosphorylation of the homodimer prevents the association of dimers into higher-order oligomers, leading to cisternal unstacking.|||Target for caspase-3 cleavage during apoptosis. The cleavage contributes to Golgi fragmentation and occurs very early in the execution phase of apoptosis.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Satb1 ^@ http://purl.uniprot.org/uniprot/E9PVB7|||http://purl.uniprot.org/uniprot/Q60611 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CUT homeobox family.|||Cleaved at Asp-254 by caspase-3 and caspase-6 during T-cell apoptosis in thymus and during B-cell stimulation. The cleaved forms cannot dimerize and lose transcription regulation function because of impaired DNA and chromatin association.|||Expressed in the subventricular zone, rostral migratory stream and in the olfactory bulb (at protein level) (PubMed:26305964). Mainly expressed in thymus, spleen, and lymph nodes with a lower level observed in the brain (PubMed:15814699).|||Interacts with PCAF. Interacts with sumoylated PML and HDAC1 Tat via the ULD domain. Interacts also with DYNLT3 and POLR2J2. Binds to EP300 (By similarity). Homodimer. Part of the nuclear protein complex gamma-globin promoter and enhancer binding factor (gamma-PE) composed at least of SATB1 and HOXB2. Interaction with CtBP1 when not acetylated stabalizes attachment to DNA and promotes transcription repression. Interacts with CUX1 (via DNA-binding domains); the interaction inhibits the attachment of both proteins to DNA.|||Mice are small in size, have disproportionately small thymi and spleens, and die at 3 weeks of age. Multiple defects in T-cell development are observed, including interrupted thymocytes differentiation and abnormal T-cell transcriptome. RNAi-mediated knockdown in neural stem/progenitor cells in the adult subventricular zone impairs early neuronal differentiation (PubMed:26305964).|||Nucleus|||PML body|||Phosphorylated by PKC. Acetylated by PCAF. Phosphorylated form interacts with HDAC1, but unphosphorylated form interacts with PCAF. DNA binding properties are activated by phosphorylation and inactivated by acetylation. In opposition, gene expression is down-regulated by phosphorylation but up-regulated by acetylation (By similarity).|||Required for the switching of fetal globin species, and beta- and gamma-globin genes regulation during erythroid differentiation. Plays a role in chromatin organization and nuclear architecture during apoptosis (By similarity). Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma. Binds to DNA at special AT-rich sequences, the consensus SATB1-binding sequence (CSBS), at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcriptional repressor controlling nuclear and viral gene expression in a phosphorylated and acetylated status-dependent manner, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Modulates genes that are essential in the maturation of the immune T-cell CD8SP from thymocytes. Promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone, possibly by positively regulating the expression of NEUROD1 (PubMed:26305964).|||Sumoylated. Sumoylation promotes cleavage by caspases.|||Up-regulated during adult neuronal stem cell differentiation. http://togogenome.org/gene/10090:Zkscan7 ^@ http://purl.uniprot.org/uniprot/E9PVW1 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Etv1 ^@ http://purl.uniprot.org/uniprot/E0CZ54|||http://purl.uniprot.org/uniprot/P41164|||http://purl.uniprot.org/uniprot/Q549J8|||http://purl.uniprot.org/uniprot/Q8CCR6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in kidney (PubMed:1340465). Moderate levels seen in the heart, brain, lung, embryo and lower levels seen in spleen, intestine, testis and thymus (PubMed:1340465).|||Belongs to the ETS family.|||Expressed in the dopaminergic neurons of the olfactory bulb at postnatal day 0 (at protein level).|||Nucleus|||Phosphorylated at Ser-191 and Ser-216 by RPS6KA1 and RPS6KA5; phosphorylation activates transcriptional activity.|||Significant reduction in the number of tyrosine hydroxylase (TH)-positive cells in the olfactory bulb.|||Sumoylated.|||Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5'-CGGA[AT]-3' (PubMed:1340465). Required for olfactory dopaminergic neuron differentiation; may directly activate expression of tyrosine hydroxylase (TH) (PubMed:19287374). http://togogenome.org/gene/10090:Nenf ^@ http://purl.uniprot.org/uniprot/Q9CQ45 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a neurotrophic factor in postnatal mature neurons, enhancing neuronal survival (PubMed:15605373, PubMed:31536960). Promotes cell proliferation and neurogenesis in undifferentiated neural pro-genitor cells at the embryonic stage and inhibits differentiation of astrocytes (PubMed:16547973). Its neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways (PubMed:15605373, PubMed:16547973). Neurotrophic activity is enhanced by binding to heme (PubMed:18056703). Acts also as an anorexigenic neurotrophic factor that contributes to energy balance (PubMed:23576617).|||Belongs to the cytochrome b5 family. MAPR subfamily.|||Endoplasmic reticulum|||In embryonic cerebral cortex is first weakly detected at 12.5 dpc, and thereafter gradually increased. At 13.5 dpc expression is observed mostly in the preplate.|||In the embryo, expressed most abundantly in brain and spinal cord. Widely expressed in adult tissues including brain, heart, lung and kidney. In brain, expressed in neurons but not in glial cells (PubMed:15605373). In the hypothalamus is expressed primarily in the paraventricular nucleus (PVN), with lower levels of expression in the arcuate nucleus (ARC)(PubMed:23576617).|||Interacts with PINK1 and PARK7.|||Mitochondrion|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residue at position 81.|||extracellular space http://togogenome.org/gene/10090:Rrh ^@ http://purl.uniprot.org/uniprot/O35214|||http://purl.uniprot.org/uniprot/Q543W9|||http://purl.uniprot.org/uniprot/Q80XL3|||http://purl.uniprot.org/uniprot/Q9D1T9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.|||Found only in the eye, where it is localized to the retinal pigment epithelium (RPE). In the RPE, it is localized to the microvilli that surround the photoreceptor outer segments.|||May play a role in rpe physiology either by detecting light directly or by monitoring the concentration of retinoids or other photoreceptor-derived compounds.|||Membrane http://togogenome.org/gene/10090:Aldob ^@ http://purl.uniprot.org/uniprot/Q3TJ66|||http://purl.uniprot.org/uniprot/Q3UER1|||http://purl.uniprot.org/uniprot/Q91Y97 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I fructose-bisphosphate aldolase family.|||Catalyzes the aldol cleavage of fructose 1,6-biphosphate to form two triosephosphates dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in glycolysis as well as the reverse stereospecific aldol addition reaction in gluconeogenesis. In fructolysis, metabolizes fructose 1-phosphate derived from the phosphorylation of dietary fructose by fructokinase into dihydroxyacetone phosphate and D-glyceraldehyde (PubMed:25637246). Acts as an adapter independently of its enzymatic activity, exerts a tumor suppressor role by stabilizing the ternary complex with G6PD and TP53 to inhibit G6PD activity and keep oxidative pentose phosphate metabolism in check (PubMed:35122041).|||Homotetramer. Interacts with BBS1, BBS2, BBS4 and BBS7. Forms a ternary complex with G6PD and TP53; this interaction is direct.|||In vertebrates, 3 forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.|||Mice are born at the expected Mendelian rate. On a fructose diet, they develop fructose intolerance associated with hepatic steatosis and mortality.|||centriolar satellite|||cytosol http://togogenome.org/gene/10090:Pex14 ^@ http://purl.uniprot.org/uniprot/Q9R0A0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peroxin-14 family.|||Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (By similarity). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix. Plays a key role for peroxisome movement through a direct interaction with tubulin (By similarity).|||Interacts with PEX13; forming the PEX13-PEX14 docking complex. Interacts with PEX5 (via WxxxF/Y motifs). Interacts with PEX19. Interacts with tubulin.|||Peroxisome membrane http://togogenome.org/gene/10090:Vmn1r56 ^@ http://purl.uniprot.org/uniprot/Q9EPS9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Lrp12 ^@ http://purl.uniprot.org/uniprot/Q8BUJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LDLR family.|||May interact with RACK1, ZFYVE9 and NMRK2.|||Membrane|||Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. May act as a tumor suppressor (By similarity).|||coated pit http://togogenome.org/gene/10090:Zkscan16 ^@ http://purl.uniprot.org/uniprot/A2ALW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Rsph6a ^@ http://purl.uniprot.org/uniprot/Q8CDR2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flagellar radial spoke RSP4/6 family.|||Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB (PubMed:36417862, PubMed:34871179). Interacts with RSPH1 (PubMed:30185526, PubMed:34871179). Interacts with RSPH3B (PubMed:34871179). Interacts with RSPH4A (PubMed:30185526). Interacts with RSPH9 (PubMed:30185526, PubMed:34871179). Interacts with RSPH10B (PubMed:30185526).|||Expressed in sperm and testis (at protein level).|||First detected during the haploid phase of spermatogenesis when secondary spermatocytes begin to appear at about postnatal day 18 (PubMed:30185526). Expression is maintained in mature sperm (PubMed:30239614).|||Functions as part of radial spoke complexes in the axoneme of sperm flagella that play an important part in motility (PubMed:36417862). The triple radial spokes (RS1, RS2 and RS3) are required to modulate beating of the sperm flagellum (PubMed:36417862, PubMed:30185526, PubMed:30239614).|||Male mutant mice are infertile. Mutant spermatozoa exhibit shorter tails, misshapen heads and immotility. Manchette removal is impaired.|||Phosphorylated by PKA. Phosphorylation increases in capacitated sperm.|||flagellum axoneme http://togogenome.org/gene/10090:Ros1 ^@ http://purl.uniprot.org/uniprot/Q78DX7 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.|||Cell membrane|||Expressed by epithelial cells of the caput epididymis (at protein level).|||Inhibited by dephosphorylation by PTPN6.|||Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling pathway. Interacts with VAV3; constitutive interaction mediating VAV3 phosphorylation (By similarity). Interacts with PTPN6 (via SH2 1 domain); the interaction is direct and promotes ROS1 dephosphorylation.|||Mice are viable and healthy. Females display normal fertility while males are sterile due a non-cell autonomous defect in sperm maturation. It is associated with the absence of tall columnar epithelial cells with long microvilli in the proximal part of the caput epididymidis.|||Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1, and PLCG2.|||Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2267 and/or Tyr-2327 recruits PTPN11 (By similarity). Phosphorylation at Tyr-2267 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation. Phosphorylation at Tyr-2267 stimulates the kinase activity and the activation of the ERK1 signaling cascade. http://togogenome.org/gene/10090:Scnn1b ^@ http://purl.uniprot.org/uniprot/A2RS45|||http://purl.uniprot.org/uniprot/Q9WU38 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by WNK1, WNK2, WNK3 and WNK4.|||Apical cell membrane|||Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1B subfamily.|||Cytoplasmic vesicle membrane|||Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (By similarity). Interacts with NEDD4 (via WW domains) (PubMed:11244092, PubMed:15123669). Interacts with NEDD4L (via WW domains) (PubMed:11244092, PubMed:12424229, PubMed:15123669). Interacts with WWP1 (via WW domains). Interacts with WWP2 (via WW domains). Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (By similarity). Interacts (N-glycosylated) with BPIFA1; the interaction is direct and inhibits the proteolytic processing of SCNN1A and SCNN1G and the activation of ENaC (By similarity).|||Lung and kidney.|||Membrane|||N-glycosylated. N-glycosylation is required for interaction with BPIFA1.|||Phosphorylated on serine and threonine residues. Aldosterone and insulin increase the basal level of phosphorylation.|||Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception. http://togogenome.org/gene/10090:Slc25a54 ^@ http://purl.uniprot.org/uniprot/B1AUS6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pak3 ^@ http://purl.uniprot.org/uniprot/Q61036 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure (By similarity).|||Autophosphorylated when activated by CDC42/p21.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK. Interacts with the C-terminal of APP. Interacts with ARHGEF6 and ARHGEF7 (By similarity). Interacts with GIT1 and GIT2 (By similarity).|||Mice show significant abnormalities in synaptic plasticity as well as deficiencies in learning and memory. Pak1 and Pak3 double knockout mice display reduced brains characterized by simplified neuronal dendrites/axons and reduced synapse density.|||Neddylated.|||Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity (PubMed:25851601). Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (PubMed:15800193). http://togogenome.org/gene/10090:Myocd ^@ http://purl.uniprot.org/uniprot/Q8VIM5 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in the cardiac crescent at 7.75 dpc and in the linear heart tube at 8.0 dpc and the developing atrial and aortic ventricular chambers until birth. Also detected in a subset of vascular and visceral smooth muscle cells: aortic arch arteries at 9.5 dpc; walls of the esophagus, dorsal aorta, pulmonary outflow tract, lung, gut, stomach, small intestine, bladder, and the head mesenchyme at 13.5 dpc until birth. Not detected in skeletal muscle cells.|||Expressed in heart, aorta, and in smooth muscle cell-containing tissues: stomach, bladder and uterus. Isoform 1 and isoform 3 are predominantly expressed in cardiac muscle whereas isoform 4 and isoform 5 are predominantly expressed in SMC-rich tissues. Isoform 3 is the most abundant isoform in the heart from embryo to adult.|||Homodimer. Interacts with MLLT7/FOXO4 (By similarity). Interacts with SRF, its association does not depend on specific DNA sequences for ternary complex formation. Interacts (via C-terminal) with EP300 (via CREB-binding domain). Interacts with HDAC4 and HDAC5. Interacts with MEF2C.|||Nucleus speckle|||Phosphorylation regulates negatively transcriptional activity.|||Smooth muscle cells (SM) and cardiac muscle cells-specific transcriptional factor which uses the canonical single or multiple CArG boxes DNA sequence. Acts as a cofactor of serum response factor (SRF) with the potential to modulate SRF-target genes. Plays a crucial role in cardiogenesis, urinary bladder development, and differentiation of the smooth muscle cell lineage (myogenesis). Isoform 1 mediates the cardiac transcription factor MEF2C-dependent transcription. Isoform 1 and isoform 3 are more active than isoform 2 and isoform 4 in stimulating cardiac muscle promoters.|||The C-terminal region contains a general transcription activation domain. The N-terminal region, comprising a basic and a Gln-rich domain, confers transcriptional potency and specificity by mediating association with the MADS box of SRF. The basic domain may be required for nuclear localization. The SAP domain is important for transactivation and ternary complex formation. http://togogenome.org/gene/10090:Ifitm7 ^@ http://purl.uniprot.org/uniprot/Q8BVR2 ^@ Similarity ^@ Belongs to the CD225/Dispanin family. http://togogenome.org/gene/10090:Epc1 ^@ http://purl.uniprot.org/uniprot/Q8C9X6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the enhancer of polycomb family.|||Component of the NuA4 histone acetyltransferase (HAT) complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:28694333). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR) (By similarity). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone acetylation is required for histone replacement during the transition from round to elongating spermatids (PubMed:28694333). In the NuA4 complex, EPC1 is required to recruit MBTD1 into the complex (By similarity).|||Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6 (By similarity). KAT5/TIP60, EPC1, and ING3 together constitute a minimal HAT complex termed Piccolo NuA4 (By similarity). Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41 (By similarity). Interacts with TRIM27 (By similarity). Interacts with MBTD1; interaction is direct and promotes recruitment of MBTD1 into the NuA4 histone acetyltransferase complex (By similarity).|||Cytoplasm|||Expressed in adult brain, heart, kidney, liver, lung, skeletal muscle and testis (PubMed:9735366). Expressed in male germ cells, present in round spermatids of steps 1 to 4 (PubMed:28694333).|||Mice are viable but display growth retardation, homeotic transformations of the axis and sterility in both males and females (PubMed:28694333). Male sterility is caused by defects in generation of elongating spermatids (PubMed:28694333).|||Nucleus http://togogenome.org/gene/10090:Tmem11 ^@ http://purl.uniprot.org/uniprot/E9Q933|||http://purl.uniprot.org/uniprot/Q8BK08 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1, MTX2 and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. Interacts with IMMT/MIC60.|||Belongs to the TMEM11 family.|||Membrane|||Mitochondrion inner membrane|||Plays a role in mitochondrial morphogenesis. http://togogenome.org/gene/10090:Itpkc ^@ http://purl.uniprot.org/uniprot/Q7TS72 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Activated by calcium/calmodulin. Inhibited by high concentrations of the substrate Ins(1,2,4)P3, and allosterically activated by the product Ins(1,3,4,5)P4.|||Belongs to the inositol phosphokinase (IPK) family.|||Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis (By similarity). Can phosphorylate inositol 2,4,5-triphosphate to inositol 2,4,5,6-tetraphosphate (By similarity).|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Or4p8 ^@ http://purl.uniprot.org/uniprot/Q8VG47 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defa28 ^@ http://purl.uniprot.org/uniprot/D3Z1V9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Gprc5d ^@ http://purl.uniprot.org/uniprot/Q0VEL2|||http://purl.uniprot.org/uniprot/Q3UUY8|||http://purl.uniprot.org/uniprot/Q9JIL6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prlr ^@ http://purl.uniprot.org/uniprot/G3UVW6|||http://purl.uniprot.org/uniprot/Q08501 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 1 subfamily.|||Interacts with SMARCA1. Interacts with NEK3 and VAV2 and this interaction is prolactin-dependent.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||This is a receptor for the anterior pituitary hormone prolactin. http://togogenome.org/gene/10090:Hnrnpul1 ^@ http://purl.uniprot.org/uniprot/Q8VDM6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Also plays a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro (By similarity).|||Interacts with BRD7, PRMT2, TP53 and NXF1. Associates with histones and BRD7 (By similarity).|||Methylated.|||Nucleus|||The RGG-box domain is methylated. http://togogenome.org/gene/10090:Top1mt ^@ http://purl.uniprot.org/uniprot/Q8R4U6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type IB topoisomerase family.|||Divalent metal ions (calcium or magnesium).|||Mitochondrion|||Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). http://togogenome.org/gene/10090:Fam169a ^@ http://purl.uniprot.org/uniprot/Q5XG69 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM169 family.|||Nucleus envelope|||Nucleus inner membrane http://togogenome.org/gene/10090:Or5h26 ^@ http://purl.uniprot.org/uniprot/E9PYP4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tasl ^@ http://purl.uniprot.org/uniprot/Q9D3J9 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Endosome membrane|||Innate immune adapter that mediates the recruitment and activation of IRF5 downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9. Following recruitment to endolysosome by SLC15A4 downstream of TLR7, TLR8 and TLR9, specifically recruits IRF5 transcription factor via its pLxIS motif, leading to IRF5 activation and subsequent expression of type I interferons. Plays a role in the regulation of endolysosomal pH in immune cells such as B-cells, dendritic cells and monocytes.|||Interacts (via pLxIS motif) with IRF5; leading to IRF5 activation. Interacts with SLC15A4; leading to its recruitment to endolysosome.|||Lysosome membrane|||Nucleus|||The pLxIS motif constitutes an IRF5-binding motif: following phosphorylation, the phosphorylated pLxIS motif of TASL recruits IRF5.|||The phosphorylated pLxIS motif constitutes an IRF5-binding motif, leading to recruitment of the transcription factor IRF5 to induce type-I interferons and other cytokines. http://togogenome.org/gene/10090:Ro60 ^@ http://purl.uniprot.org/uniprot/O08848|||http://purl.uniprot.org/uniprot/Q3TJ75 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Ro 60 kDa family.|||Cilia absent or reduced, virtually no cilia of the normal 5 uM mean length.|||Cytoplasm|||Highest in brain, followed by lung, muscle, kidney and heart. Lower levels are found in testis, liver and spleen.|||Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Found in a complex with PUF60 and Y5 RNA (By similarity). Interacts with RAB11FIP5 (By similarity).|||RNA-binding protein that binds to misfolded non-coding RNAs, pre-5S rRNA, and several small cytoplasmic RNA molecules known as Y RNAs (By similarity). May play roles in cilia formation and/or maintenance (PubMed:21289087).|||The MIDAS-like motif in the VWFA-like domain binds divalent metal cations.|||The horseshoe-shaped TROVE domain is built with 7 helical HEAT-like repeats, and is closed by the VWFA-like domain giving rise to a ring-shaped monomer. Single-stranded RNA is bound in the positively charged central cavity (By similarity). http://togogenome.org/gene/10090:Tbxas1 ^@ http://purl.uniprot.org/uniprot/P36423|||http://purl.uniprot.org/uniprot/Q3UTF0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Catalyzes the conversion of prostaglandin H2 (PGH2) to thromboxane A2 (TXA2), a potent inducer of blood vessel constriction and platelet aggregation. Cleaves also PGH2 to 12-hydroxy-heptadecatrienoicacid (12-HHT) and malondialdehyde, which is known to act as a mediator of DNA damage. 12-HHT and malondialdehyde are formed stoichiometrically in the same amounts as TXA2. Additionally, displays dehydratase activity, toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) producing 15-KETE and 15-HETE.|||Deficient mice are viable, fertile and exhibited no gross abnormalities in size, body weight, and anatomical features of major organs. However deficency causes a mild hemostatic defect and protects mice against arachidonate-induced shock and death.|||Endoplasmic reticulum membrane|||Expressed primarily in lung, kidney, and spleen.|||Monomer. http://togogenome.org/gene/10090:Hbb-bt ^@ http://purl.uniprot.org/uniprot/A8DUK4|||http://purl.uniprot.org/uniprot/P02088 ^@ Function|||Miscellaneous|||Polymorphism|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the globin family.|||Heterotetramer of two alpha chains and two beta chains.|||Inbred mouse strains possess 1 of 4 alleles at the HBB locus: D (diffuse), S (single), P and W1. The D and P alleles are actually closely linked doublets that coordinately express a major and a minor chain, the minor chain being slightly different in the two alleles. The S allele produces only 1 chain, it is characteristic of North American wild mice. The W1 allele is observed mainly in Northwestern China.|||Involved in oxygen transport from the lung to the various peripheral tissues.|||Red blood cells.|||The D-major sequence is shown. See also the entry for the beta D and P-minor chain. http://togogenome.org/gene/10090:Gm10096 ^@ http://purl.uniprot.org/uniprot/Q62478 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Acbd6 ^@ http://purl.uniprot.org/uniprot/Q9D061 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Binds long-chain acyl-coenzyme A molecules with a strong preference for unsaturated C18:1-CoA, lower affinity for unsaturated C20:4-CoA, and very weak affinity for saturated C16:0-CoA. Does not bind fatty acids (By similarity).|||Cytoplasm|||Monomer. http://togogenome.org/gene/10090:Plxnc1 ^@ http://purl.uniprot.org/uniprot/Q9QZC2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Detected on dendritic cells, skin Langerhans cells and neutrophils (at protein level).|||Membrane|||Monomer. Homodimer. Interacts with SEMA7A (By similarity).|||No visible phenotype.|||Receptor for SEMA7A, for vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8 (By similarity). http://togogenome.org/gene/10090:Tmem50a ^@ http://purl.uniprot.org/uniprot/Q52KP1|||http://purl.uniprot.org/uniprot/Q9CXL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UPF0220 family.|||Membrane http://togogenome.org/gene/10090:Tep1 ^@ http://purl.uniprot.org/uniprot/P97499 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated component of the telomerase holoenzyme complex (By similarity). Component of the vault ribonucleoprotein particle, at least composed of MVP, PARP4 and one or more vault RNAs (vRNAs) (PubMed:11149928, PubMed:9020079). Binds to VAULTRC1, VAULTRC2 and VAULTRC4/hvg4 vRNAs (PubMed:11149928, PubMed:9020079).|||Component of the telomerase ribonucleoprotein complex that is essential for the replication of chromosome termini (By similarity). Also a component of the ribonucleoprotein vaults particle, a multi-subunit structure involved in nucleo-cytoplasmic transport (PubMed:11149928). Responsible for the localizing and stabilizing vault RNA (vRNA) association in the vault ribonucleoprotein particle (PubMed:11149928).|||Nucleus|||Ubiquitous.|||telomere http://togogenome.org/gene/10090:Vmn2r122 ^@ http://purl.uniprot.org/uniprot/O35190 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:H2-Ob ^@ http://purl.uniprot.org/uniprot/O35424|||http://purl.uniprot.org/uniprot/Q3U1X7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Cdr2 ^@ http://purl.uniprot.org/uniprot/P97817 ^@ Similarity|||Tissue Specificity ^@ Belongs to the CDR2 family.|||Expressed in brain and testis (at protein level). Expressed in the cerebellum, cerebral cortex, heart, lung, spleen, ovary, kidney and testis. http://togogenome.org/gene/10090:Lyz3 ^@ http://purl.uniprot.org/uniprot/Q8BM26|||http://purl.uniprot.org/uniprot/Q8BM27 ^@ Similarity ^@ Belongs to the glycosyl hydrolase 22 family. http://togogenome.org/gene/10090:Zfyve16 ^@ http://purl.uniprot.org/uniprot/Q80U44 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Early endosome membrane|||Interacts (via C-terminus) with TOM1 (via C-terminus); interaction is required to target TOM1 to endosomes (By similarity). Does not interact with TOM1L1 or TOM1L2 (By similarity).|||May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes (By similarity).|||The FYVE-type zinc finger is necessary and sufficient for its localization into early endosomes and mediates the association with PI3P. http://togogenome.org/gene/10090:Lrrc8c ^@ http://purl.uniprot.org/uniprot/Q8R502 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LRRC8 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed at very low levels in adipose tissue.|||Heterohexamer (PubMed:29769723). Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:29769723). Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity). In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable).|||Induced during the earliest stages of adipogenesis.|||Mice do not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but display significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Moreover, improved insulin resistance induced by the high-fat diet is observed.|||Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Plays a redundant role in the efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (By similarity). The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (By similarity). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (By similarity). May play a role in adipogenesis (PubMed:15184384, PubMed:15564382, PubMed:21804215).|||The cytoplasmic N-terminus preceding the first transmembrane (residues 1-22) regulates volume-regulated anion channel (VRAC) conductance, ion permeability and inactivation gating.|||The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins. http://togogenome.org/gene/10090:Shd ^@ http://purl.uniprot.org/uniprot/O88834 ^@ Function|||PTM|||Tissue Specificity ^@ May function as an adapter protein.|||Specifically expressed in brain.|||Tyrosine phosphorylated by ABL. http://togogenome.org/gene/10090:Sbf2 ^@ http://purl.uniprot.org/uniprot/E9PXF8 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 1433 in the dsPTPase catalytic loop, suggesting that it has no phosphatase activity.|||Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Endosome membrane|||Expressed in sciatic nerve and in Schwann cells (at protein level) (PubMed:16750429, PubMed:16399794, PubMed:17855448, PubMed:18349142, PubMed:23297362). Expressed in brain (at protein level) (PubMed:18349142, PubMed:22648168). Highly expressed in brain, heart, kidney and testis, and to a lesser extent in lung, stomach, small intestine, skeletal muscle, liver and placenta (PubMed:16750429). Expressed in spinal cord and eye (PubMed:16750429). Not expressed in thymus and spleen (PubMed:16750429).|||Guanine nucleotide exchange factor (GEF) which activates RAB21 and possibly RAB28 (By similarity). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (By similarity). In response to starvation-induced autophagy, activates RAB21 which in turn binds to and regulates SNARE protein VAMP8 endolysosomal transport required for SNARE-mediated autophagosome-lysosome fusion (By similarity). Acts as an adapter for the phosphatase MTMR2 (PubMed:16399794). Increases MTMR2 catalytic activity towards phosphatidylinositol 3,5-bisphosphate and to a lesser extent towards phosphatidylinositol 3-phosphate (PubMed:16399794).|||Homodimer (PubMed:16399794). Heterotetramer consisting of one MTMR2 dimer and one SBF2/MTMR13 dimer (PubMed:16399794). Interacts with class II PI3-kinase PIK3C2A (PubMed:22648168). Interacts (via DENN domain) with RAB21 (in GDP-bound form) in response to starvation; the interaction activates RAB21 (By similarity). Interacts with VAMP8 in response to starvation (By similarity).|||In 9 dpc embryos, strongly expressed in the craniofacial region, the branchial arches and in limb buds. Also expressed in brain and along the neural tube. At 9 dpc and 10 dpc, no expression is detected in the heart but at later stages expressed weakly in the ventricle. At 11 dpc and 12 dpc, highly expressed in the neural tube, limb bud, dorsal trunk and tail mesenchyme. In the brain of 13 dpc embryos, highly expressed in the cortex and the dorsal spinal cord and weakly in midbrain.|||MTMR2 protein levels are decreased in sciatic nerves but not in the brain (PubMed:18349142, PubMed:23297362). However, MTMR2 protein levels have also been shown not to be affected in sciatic nerves (PubMed:17855448).|||Membrane|||Mice are born at the expected Mendelian rate (PubMed:18349142). Display demyelinating peripheral neuropathy characterized by slowed nerve conduction velocity, axon degeneration, and myelin outfolding and infolding in motor and sensory peripheral nerves (PubMed:17855448, PubMed:18349142, PubMed:23297362). Defects in myelination start to appear at postnatal day 3 (P3) (PubMed:23297362). The neuropathy severity increases with age (PubMed:17855448, PubMed:23297362).|||The C-terminal domain mediates homodimerization (PubMed:16399794). By mediating SBF2/MTMR13 homodimerization, indirectly involved in SBF2/MTMR13 and MTMR2 homotetramerization (PubMed:16399794).|||The GRAM domain mediates binding to phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3,4,5-trisphosphate.|||The PH domain binds preferentially phosphatidylinositol 3,4,5-trisphosphate (PubMed:16399794). Appears to be dispensable for localization to membranes (PubMed:23297362).|||axon|||perinuclear region http://togogenome.org/gene/10090:Pnpla1 ^@ http://purl.uniprot.org/uniprot/B2KF06|||http://purl.uniprot.org/uniprot/Q3V1D5 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Homozygous knockout mice lacking Pnpla1 are obtained at the expected Mendelian ratio but die within 24 hours after birth (PubMed:27751867, PubMed:28248300). They display shiny and taut skin, often with a necrotic tail tip (PubMed:27751867, PubMed:28248300). They are less active, markedly smaller, and weighed significantly less than their wild-type counterpart (PubMed:27751867). Unique linoleate-containing lipids including acylceramides, acylglucosylceramides and (O-acyl)-omega-hydroxy fatty acids are almost absent in the epidermis while there is a reciprocal increase in their putative precursors (PubMed:27751867, PubMed:28248300). The absence of these highly hydrophobic linoleate-containing lipids in the epidermis is responsible for the lethal disruption of the epidermal permeability barrier which is characterized by a decrease in intercellular lipid lamellae in the stratum corneum, the loss or abnormalities of the cornified lipid envelope, and aberrant keratinocyte differentiation (PubMed:27751867, PubMed:28248300). Keratinocyte-specific conditional knockout mice also die shortly after birth, displaying desquamation with alteration of the stratum corneum and of the lipid composition of the epidermis (PubMed:28248300).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation (PubMed:27751867, PubMed:28248300). Catalyzes the last step of the synthesis of omega-O-acylceramides by transferring linoleic acid from triglycerides to an omega-hydroxyceramide (PubMed:27751867, PubMed:28248300). Omega-O-acylceramides, are required for the biogenesis of lipid lamellae in the stratum corneum and the formation of the cornified lipid envelope which are essential for the epidermis barrier function (PubMed:27751867, PubMed:28248300). These lipids also play a role in keratinocyte differentiation (PubMed:28248300). May also act on omega-hydroxylated ultra-long chain fatty acids (omega-OH ULCFA) and acylglucosylceramides (GlcEOS) (PubMed:28248300).|||Specifically expressed in skin by keratinocytes, at the boundary area between the nucleated stratum granulosum and the denucleated stratum corneum in the epidermis (at protein level) (PubMed:28248300). Also expressed in stomach and other surface lining tissues like intestine and tongue (PubMed:27751867, PubMed:28248300). Also detected in testis as well as in other tissues but at very low level (PubMed:28248300).|||Up-regulated upon induced differentiation of keratinocytes. http://togogenome.org/gene/10090:H2bc12 ^@ http://purl.uniprot.org/uniprot/B2RVD5|||http://purl.uniprot.org/uniprot/Q8CGP1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Fkbp8 ^@ http://purl.uniprot.org/uniprot/O35465 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds the immunosuppressant FK506 only in its calmodulin/calcium activated form.|||Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis (By similarity). Required for normal embryonic development.|||Detected throughout the embryonic body, in caudal neural tube, limbs and head. Detected in adult retina, brain, heart, kidney, liver, pancreas, lung, testis and urinary bladder (at protein level). Detected in adult brain, kidney, liver, testis and trigeminal nerve, and in embryo. Detected at lower levels in lung, spleen, heart and ovary. Widely expressed in forebrain. Detected in the Purkinje cell layer in the cerebellum and in hippocampus neurons.|||Homomultimers or heteromultimers (Potential). Forms heterodimer with calmodulin. When activated by calmodulin and calcium, interacts with the BH4 domain of BCL2 and weakly with BCLX isoform Bcl-X(L). Does not bind and inhibit calcineurin (By similarity). Interacts with ZFYVE27; may negatively regulate ZFYVE27 phosphorylation (By similarity).|||Mice die shortly after birth. They display neural tube and skeletal defects. The neuroepithelium is disorganized and the formation of dorsal root ganglia is defective, likely as a result of an increased frequency of apoptosis and aberrant migration of neuronal cells. The extension of nerve fibers in the spinal cord is also abnormal.|||Mitochondrion membrane|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30. http://togogenome.org/gene/10090:Pltp ^@ http://purl.uniprot.org/uniprot/P55065|||http://purl.uniprot.org/uniprot/Q3UE59|||http://purl.uniprot.org/uniprot/Q3UFS5 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||Glycosylation is necessary for secretion and its phospholipid transfer activity.|||Highest level expression in the lung, brain and heart with relatively low levels in the liver, skeletal muscle and testis and very low levels found in the spleen and kidney.|||Mediates the transfer of phospholipids and free cholesterol from triglyceride-rich lipoproteins (low density lipoproteins or LDL and very low density lipoproteins or VLDL) into high-density lipoproteins (HDL) as well as the exchange of phospholipids between triglyceride-rich lipoproteins themselves (PubMed:7654777, PubMed:7615508, PubMed:10079112). Facilitates the transfer of a spectrum of different lipid molecules, including sphingomyelin, phosphatidylcholine, phosphatidylinositol, phosphatidylglycerol, and phosphatidyl ethanolamine (PubMed:10079112). Plays an important role in HDL remodeling which involves modulating the size and composition of HDL (By similarity). Also plays a key role in the uptake of cholesterol from peripheral cells and tissues that is subsequently transported to the liver for degradation and excretion (By similarity). Two distinct forms of PLTP exist in plasma: an active form that can transfer phosphatidylcholine from phospholipid vesicles to HDL, and an inactive form that lacks this capability (By similarity).|||Mice show a complete loss of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and sphingomyelin transfer activities, and a partial loss of free cholesterol transfer activity (PubMed:10079112). Transfer of VLDL phospholipid into HDL is abolished (PubMed:10079112). A marked reduction in the levels of plasma HDL phospholipid, cholesteryl ester and free cholesterol seen, whereas the levels of non-HDL lipids are not significantly altered (PubMed:10079112).|||Nucleus|||Secreted http://togogenome.org/gene/10090:Bbox1 ^@ http://purl.uniprot.org/uniprot/Q924Y0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the gamma-BBH/TMLD family.|||Binds 1 Fe(2+) ion per subunit.|||Catalyzes the formation of L-carnitine from gamma-butyrobetaine.|||Cytoplasm http://togogenome.org/gene/10090:Or1i2 ^@ http://purl.uniprot.org/uniprot/Q7TQU7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm11437 ^@ http://purl.uniprot.org/uniprot/Q5QR91 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cpq ^@ http://purl.uniprot.org/uniprot/Q9WVJ3 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Aberrant splicing.|||Belongs to the peptidase M28 family.|||Carboxypeptidase that may play an important role in the hydrolysis of circulating peptides. Catalyzes the hydrolysis of dipeptides with unsubstituted terminals into amino acids. May play a role in the liberation of thyroxine hormone from its thyroglobulin (Tg) precursor (By similarity).|||Endoplasmic reticulum|||Golgi apparatus|||Homodimer. The monomeric form is inactive while the homodimer is active (By similarity).|||Lysosome|||N-glycosylated. The secreted form is modified by hybrid or complex type oligosaccharide chains.|||Secreted http://togogenome.org/gene/10090:Med6 ^@ http://purl.uniprot.org/uniprot/A0A0R4IZX3|||http://purl.uniprot.org/uniprot/E0CYA6|||http://purl.uniprot.org/uniprot/Q921D4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 6 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CTNNB1 and GLI3 (By similarity).|||Component of the Mediator complex.|||Nucleus http://togogenome.org/gene/10090:Exo1 ^@ http://purl.uniprot.org/uniprot/Q9QZ11 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis.|||Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.|||Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.|||Highly expressed in the spleen and testis. Also expressed in the bone marrow, brain, lung, lymph node and thymus.|||Interacts with the MLH1-PMS2 heterodimer via MLH1. Interacts with MSH3. Interacts with the MSH2-MSH6 heterodimer via MSH2, and this interaction may increase the processivity of the 5'->3' exonuclease activity. Interacts with PCNA, and this interaction may both stimulate the cryptic 3'->5' exonuclease activity and suppress the 5'->3' exonuclease activity. Interacts with WRN, and this interaction stimulates both the 5'->3' exonuclease activity and cleavage of 5'-overhanging flap structures. Interacts with RECQL/RECQ1, and this interaction stimulates cleavage of 5'-overhanging flap structures (By similarity).|||Nucleus|||Phosphorylated upon DNA damage and in response to agents stalling DNA replication, probably by ATM or ATR.|||Postnatal expression in the testis is elevated at the onset of pachytene (day 14). http://togogenome.org/gene/10090:Cldn34c2 ^@ http://purl.uniprot.org/uniprot/A0A571BG29 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Pitx2 ^@ http://purl.uniprot.org/uniprot/B1VD84|||http://purl.uniprot.org/uniprot/B1VD85|||http://purl.uniprot.org/uniprot/P97474|||http://purl.uniprot.org/uniprot/Q6DIA6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paired homeobox family. Bicoid subfamily.|||Controls cell proliferation in a tissue-specific manner and is involved in morphogenesis. During embryonic development, exerts a role in the expansion of muscle progenitors. May play a role in the proper localization of asymmetric organs such as the heart and stomach. Isoform Ptx2c is involved in left-right asymmetry the developing embryo.|||Expressed in the embryonic heart. Expressed in the left lateral plate mesoderm and symmetrically in the head mesoderm at 8.5 dpc. Isoform Ptx2c is expressed in the ventral outflow tract region (OFT), right ventricle (RV) and in the left atrium of the heart.|||In day-11 embryos, expressed in the periocular mesenchyme, maxillary and mandibular epithelia, umbilicus, Rathke pouch, vitelline vessels and limb mesenchyme. In adult tissues, expressed in pituitary gland, brain, kidney, eye, lung, testis and tongue.|||Interacts with PITX2.|||Mice embryos lacking isoform Ptx2c show left-right patterning defects and severe developmental abnormalities.|||Nucleus|||Phosphorylation at Thr-90 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1.|||Produced by alternative initiation at Met-35 of isoform Ptx2C. http://togogenome.org/gene/10090:Sh2d2a ^@ http://purl.uniprot.org/uniprot/Q9QXK9 ^@ Function|||Induction|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Could be a T-cell-specific adapter protein involved in the control of T-cell activation. May play a role in p56-LCK-mediated T-cell signaling. Could be involved in the regulation of responses to T-cell activation stimuli, specifically proliferation and lymphokine production. Interactions with ITK and TXK may provide important biochemical links of these two important kinases with other components in the T-cell activation machinery.|||Cytoplasm|||Expression limited to tissues of the immune system and, in particular, activated T-cells and natural killer cells. Expressed in the thymus, lymph node, and to a lesser extent, in the spleen and bone marrow. According to PubMed:10553045, also expressed in the lung.|||Interacts with KDR (By similarity). Interacts with p56-LCK, TXK and ITK.|||Phosphorylated on tyrosine residues upon TCR-stimulation.|||Proliferation of SH2D2A-deficient T-cells in response to T-cell receptor (TCR)-mediated activation is significantly impaired. These activated T-cells are defective in the production of interleukin (IL)-2 and interferon gamma, but not IL-4.|||Up-regulated substantially after T-cell activation. http://togogenome.org/gene/10090:Fktn ^@ http://purl.uniprot.org/uniprot/A0A1Y7VM91|||http://purl.uniprot.org/uniprot/Q8R507 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LicD transferase family.|||Catalyzes the transfer of CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1) (PubMed:12471058). This constitutes the first step in the formation of the ribitol 5-phosphate tandem repeat which links the phosphorylated O-mannosyl trisaccharide to the ligand binding moiety composed of repeats of 3-xylosyl-alpha-1,3-glucuronic acid-beta-1 (By similarity). Required for normal location of POMGNT1 in Golgi membranes, and for normal POMGNT1 activity (PubMed:19017726). May interact with and reinforce a large complex encompassing the outside and inside of muscle membranes (PubMed:19017726, PubMed:22922256). Could be involved in brain development (Probable).|||Cytoplasm|||Embryonic lethality (PubMed:19017726). However, when human FCMD disease-causing retrotransposon is introduced into the mouse fukutin gene, alpha-dystroglycan/DAG1 is hypoglycosylated in muscles as is seen in FCMD (congenital muscular dystrophy Fukuyama) patients. Transfer of normal fukutin gene into these knockin mice restores glycosylation of alpha-dystroglycan (PubMed:19017726). Conditional knockout in muscle results in near absence of glycosylated dystroglycan within 18 days of gene deletion. 20 week-old knockout mice show clear dystrophic histopathology and defects in glycosylation near the dystroglycan O-mannose phosphate when excision driven by muscle-specific promoters takes place at 8 dpc or 17 dpc. Earlier gene deletion causes more severe phenotypes (PubMed:22922256).|||Endoplasmic reticulum|||Expressed in the retina, with highest levels found in the inner segments of photoreceptors and the outer plexiform layer (at protein level) (PubMed:29416295). Expressed at lower levels in the inner and outer nuclear layers, the inner plexiform layers, and the ganglion cell layers of the retina (at protein level) (PubMed:29416295). Expressed in the heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis (PubMed:12471058, PubMed:12408965).|||Forms a complex composed of FKTN/fukutin, FKRP and RXYLT1/TMEM5 (By similarity). Interacts (via transmembrane domain) with POMGNT1; the interaction is direct and is required for normal POMGNT1 location in Golgi membranes (By similarity).|||Golgi apparatus membrane|||Nucleus|||Wide distribution of expression throughout embryonic development, most predominantly in the central and peripheral nervous systems. High expression in the ventricular zone of proliferating neurons at 13.5 dpc. Broadly expressed in late embryonic and early postnatal cerebellar neurons, including premigratory granule neurons of the external granule cell layer. Expression is maintained in neurons of the internal granule cell layer after migration is complete. Intense expression in Purkinje cells throughout development. A unique pattern of intense expression in irregularly spaced cell bodies that do not appear to correlate with known parasagittal stripes. Expressed in Bergmann glial scaffolds used by granule cells during early posnatal radial migration. http://togogenome.org/gene/10090:Pura ^@ http://purl.uniprot.org/uniprot/P42669 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PUR DNA-binding protein family.|||Homodimer, heterodimer with PURB and heterotrimer with PURB and YBX1/Y-box protein 1 (PubMed:10318844). Interacts with FMR1; this interaction occurs in association with polyribosome (PubMed:12147688).|||Nucleus|||This is a probable transcription activator that specifically binds the purine-rich single strand of the PUR element located upstream of the c-Myc gene. May play a role in the initiation of DNA replication and in recombination. http://togogenome.org/gene/10090:Bhlhe41 ^@ http://purl.uniprot.org/uniprot/Q99PV5 ^@ Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activity profiles and sleep recordings of transgenic mice carrying the mutation Arg-325 show increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner.|||Expressed in a circdadian manner in the liver with a peak at ZT10.|||Expressed in skeletal muscle, brain and lung.|||Homodimer (PubMed:15560782). Heterodimer with BHLHE40/DEC1 (PubMed:15560782). Interacts with CIART (PubMed:24736997). Interacts with BMAL1 (PubMed:12397359). Interacts with RXRA (By similarity). Interacts with NR0B2 and HNF1A (PubMed:30555544).|||Nucleus|||Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 and CYP3A11 (PubMed:30555544). http://togogenome.org/gene/10090:Ptdss1 ^@ http://purl.uniprot.org/uniprot/Q99LH2 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the phosphatidyl serine synthase family.|||Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (PubMed:10432300, PubMed:9516423, PubMed:18343815, PubMed:10938271). Catalyzes mainly the conversion of phosphatidylcholine (PubMed:9516423, PubMed:18343815, PubMed:10432300, PubMed:10938271). Also converts, in vitro and to a lesser extent, phosphatidylethanolamine (PubMed:10432300, PubMed:9516423, PubMed:18343815, PubMed:10938271).|||Endoplasmic reticulum membrane|||Expressed in kidney, testis, lung, skeletal muscle, liver brain, heart and spleen with highest expression in testis, liver, heart and brain.|||Null mice are viable, fertile and have a normal life span. Toal serine exchange is reduced up to 85%, but apart from in liver, the phosphatatidylserine content was unaltered. Elimination of either Pss1 or Pss2, but not both, is compatible with mouse viability. Mice can tolerate as little as 10% serine-exchange activity and are viable with small amounts of phosphatidylserine and phosphatidylethanolamine content. to phosphatidylethanolamine.|||Potently inhibited by choline in the mitochondria-associated membrane (MAM). Very little inhibition by choline in the endoplasmic reticulum (ER) per se. http://togogenome.org/gene/10090:Vmn1r259 ^@ http://purl.uniprot.org/uniprot/D3YTX5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Sv2c ^@ http://purl.uniprot.org/uniprot/Q69ZS6 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with C.botulinum neurotoxin type A (BoNT/A, botA).|||(Microbial infection) Interacts with C.botulinum neurotoxin type D (BoNT/D, botD).|||(Microbial infection) Possible receptor for C.botulinum neurotoxin type D (BoNT/D, botD) (PubMed:21483489).|||(Microbial infection) Receptor for C.botulinum neurotoxin type A (BoNT/A, botA); the toxin binds Sv2c via extracellular loop 4 (PubMed:16543415).|||Belongs to the major facilitator superfamily.|||Expressed during synaptogenesis in the retina (at protein level).|||Expressed in specific subsets of conventional synapses in the retina (at protein level) (PubMed:12687700). Expressed in diaphragm motor nerve terminals (at protein level) (PubMed:16543415). Expressed in a subset of hippocampus neurons (at protein level) (PubMed:18815274, PubMed:21483489).|||Interacts with SYT1 in a calcium-dependent manner.|||N-glycosylated.|||Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission. Positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles.|||Small interfering RNA knockdown of the protein in Neuro-2a cells (which only express this SV2 protein) prevents uptake of C.botulinum neurotoxin type A (BoNT/A, botA); uptake is restored by expression of rat SV2A or SV2B (PubMed:16543415).|||The use of this protein as a coreceptor for C.botulinum type D (BoNT/D, botD) is controversial. In double SV2A/SV2B knockout mice BoNT/D does not degrade its synaptobrevin target; introducing SV2A, SV2B or SV2C restores target cleavage (PubMed:21483489). However another group does not find a convincing interaction with SV2 (PubMed:21632541).|||Up-regulated upon Sv2a depletion.|||synaptic vesicle membrane http://togogenome.org/gene/10090:Jak1 ^@ http://purl.uniprot.org/uniprot/B1ASP2|||http://purl.uniprot.org/uniprot/Q3U8P8|||http://purl.uniprot.org/uniprot/Q3URU8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.|||Endomembrane system http://togogenome.org/gene/10090:Zmiz2 ^@ http://purl.uniprot.org/uniprot/Q8CIE2 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Increases ligand-dependent transcriptional activity of AR and other nuclear hormone receptors.|||Interacts with AR, SMARCA4/BRG1 and SMARCE1/BAF57. Interaction with either SMARCA4 and SMARCE1 enhances AR-mediated transcription (By similarity).|||May be due to a competing acceptor splice site.|||Nucleus http://togogenome.org/gene/10090:Yipf5 ^@ http://purl.uniprot.org/uniprot/Q9EQQ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the YIP1 family.|||COPII-coated vesicle|||Endoplasmic reticulum membrane|||Interacts with the COPII coat components Sec23 (SEC23A and/or SEC23B) and Sec24 (SEC24A and/or SEC24B) (By similarity). Interacts with YIF1A (By similarity). May interact with RAB1A (By similarity). Interacts with YIPF3 and YIPF4 (By similarity).|||Plays a role in transport between endoplasmic reticulum and Golgi. In pancreatic beta cells, required to transport proinsulin from endoplasmic reticulum into the Golgi.|||Ubiquitously expressed.|||cis-Golgi network membrane http://togogenome.org/gene/10090:Nagpa ^@ http://purl.uniprot.org/uniprot/Q8BJ48 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step. Also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases.|||Golgi stack membrane|||Homotetramer arranged as two disulfide-linked homodimers. Interacts with AP4M1.|||The C-terminal NPFKD sequence is an attractive candidate for either an endocytosis signal acting at the plasma membrane or a retrieval signal acting at the TGN to return the enzyme to the cis/medial-Golgi.|||The precursor is cleaved and activated in the trans-Golgi network by a furin endopeptidase.|||The tyrosine-based internalization signal may be essential for its retrieval from the plasma membrane to the TGN.|||trans-Golgi network http://togogenome.org/gene/10090:Meikin ^@ http://purl.uniprot.org/uniprot/Q5F2C3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Appears at centromeres during the pachytene stage, when homologous chromosomes are synapsed. Peaks during diplotene stage, persists with gradual reduction until metaphase I, and disappears in anaphase I. Does not reappear on chromatin in meiosis II.|||Germ cell-specific. Expressed in both testis and ovary. Not expressed in other tissues.|||Infertility due to defects in meiosis. Mice develop normally and show no visible phenotype but are completely infertile (both males and females) due to defects in meiotic chromosome segregation during meiosis I. Monooriented kinetochores split prematurely and sister chromosomes separate entirely before anaphase of meiosis II.|||Interacts with CENPC. Interacts with PLK1; required for recruitment of PLK1 at kinetochores.|||Key regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage. Acts by facilitating kinetochore mono-orientation during meiosis I, when kinetochores on sister chromosomes face the same direction and are thus captured and pulled by spindle fibers from the same pole. Also required to prevent cleavage of cohesin at centromeres during meiosis I, possibly by acting as a regulator of the shugoshin-dependent protection pathway. Acts in collaboration with PLK1: required for PLK1 enrichment to kinetochores. Not required during meiosis II or mitosis.|||centromere|||kinetochore http://togogenome.org/gene/10090:Dnaja3 ^@ http://purl.uniprot.org/uniprot/Q99M87 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with JAK2, HSPA9B and IFN-gammaR2 chain. Interacts with Ras GTPase-activating protein 1 (RASA1). Isoform 2 interacts with MUSK (via the cytoplasmic domain).|||Mitochondrion matrix|||Modulates apoptotic signal transduction or effector structures within the mitochondrial matrix. Affect cytochrome C release from the mitochondria and caspase 3 activation, but not caspase 8 activation. Isoform 1 increases apoptosis triggered by both TNF and the DNA-damaging agent mytomycin C; in sharp contrast, isoform 2 suppresses apoptosis. Can modulate IFN-gamma-mediated transcriptional activity (By similarity). Isoform 2 may play a role in neuromuscular junction development as an effector of the MUSK signaling pathway.|||Modulation of apoptosis, i.e. proapoptotic activity of isoform 1 and antiapoptotic activity of isoform 2, is J domain-dependent (By similarity).|||Postsynaptic cell membrane|||Tyrosine phosphorylated.|||cytosol http://togogenome.org/gene/10090:Gm20851 ^@ http://purl.uniprot.org/uniprot/A0A0A6YXW2 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Iscu ^@ http://purl.uniprot.org/uniprot/Q9D7P6 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NifU family.|||Cysteine persulfide is reduced by thiol-containing molecules such as glutathione and L-cysteine.|||Homodimer; Tyr-36-mediated dimerization of two iron- and sulfide-containing ISCU subunit bind to the cysteine desulfurase complex (By similarity). Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer (By similarity). Interacts (D-state) with NFS1 (homodimer form); each monomer interacts with the C-terminal regions of each NFS1 monomer. Interacts (monomer form) with FXN (via ferrous form); the interaction is possible when both are bound to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4) and enhances FXN interaction to the dimeric form of the cysteine desulfurase complex (NFS1:LYRM4). Interacts with GLRX5. Interacts (D-state) with HSPA9. Interacts (S-state) with HSCB; this interaction stimulates the ATPase activity of HSPA9 (By similarity). Component of a complex composed of FXN, NFS1, LYRM4 and ISCU (PubMed:21298097, PubMed:25597503).|||Mitochondrial scaffold protein, of the core iron-sulfur cluster (ISC) assembly complex, that provides the structural architecture on which the [2Fe-2S] clusters are assembled. The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5. Exists as two slow interchanging conformational states, a structured (S) and disordered (D) form. May modulate NFS1 desulfurase activity in a zinc-dependent manner. Modulates the interaction between FXN and the cysteine desulfurase complex.|||Mitochondrion|||Phosphorylation at Ser-15 is required for ISCU protein stabilization in the cytosol, whereas dephosphorylation of Ser-15, due to the inhibition of mTORC1 (mammalian target of rapamycin complex 1) complex, leads to degradation of the precursor form and ultimately to a decrease in the mitochondrial mature form.|||Previous publications report that ISCU could provide the architecture on which both [2Fe-2S] and [4Fe-4S] clusters could be assembled (By similarity). Recent reports confirm that only [2Fe-2S] clusters are formed by the core ISC assembly complex (By similarity). http://togogenome.org/gene/10090:Or4k35 ^@ http://purl.uniprot.org/uniprot/Q8VF41 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slco6d1 ^@ http://purl.uniprot.org/uniprot/Q14DL2|||http://purl.uniprot.org/uniprot/Q9D5W6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the organo anion transporter (TC 2.A.60) family.|||Membrane http://togogenome.org/gene/10090:Sds ^@ http://purl.uniprot.org/uniprot/Q8VBT2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the serine/threonine dehydratase family.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Or7g19 ^@ http://purl.uniprot.org/uniprot/Q7TRG9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aifm1 ^@ http://purl.uniprot.org/uniprot/B1AU25|||http://purl.uniprot.org/uniprot/Q9Z0X1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAD-dependent oxidoreductase family.|||Cytoplasm|||Expressed in cortical neurons (at protein level).|||Expressed in liver (at protein level).|||Functions both as NADH oxidoreductase and as regulator of apoptosis (By similarity). In response to apoptotic stimuli, it is released from the mitochondrion intermembrane space into the cytosol and to the nucleus, where it functions as a proapoptotic factor in a caspase-independent pathway (PubMed:9989411, PubMed:12114629, PubMed:21467298). Release into the cytoplasm is mediated upon binding to poly-ADP-ribose chains (PubMed:21467298). The soluble form (AIFsol) found in the nucleus induces 'parthanatos' i.e. caspase-independent fragmentation of chromosomal DNA (PubMed:9989411, PubMed:12114629, PubMed:21467298). Binds to DNA in a sequence-independent manner (PubMed:21467298). Interacts with EIF3G, and thereby inhibits the EIF3 machinery and protein synthesis, and activates caspase-7 to amplify apoptosis (By similarity). Plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells (By similarity). In contrast, participates in normal mitochondrial metabolism. Plays an important role in the regulation of respiratory chain biogenesis by interacting with CHCHD4 and controlling CHCHD4 mitochondrial import (PubMed:19447115).|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion intermembrane space|||Monomer (oxidized form). Homodimer (reduced form) (By similarity). Upon reduction with NADH, undergoes dimerization and forms tight, long-lived FADH2-NAD charge transfer complexes (CTC) resistant to oxidation (PubMed:19447115). Also dimerizes with isoform 3 preventing its release from mitochondria (By similarity). Interacts with XIAP/BIRC4 (By similarity). Interacts (via N-terminus) with EIF3G (via C-terminus) (By similarity). Interacts with PRELID1 (By similarity). Interacts with CHCHD4; the interaction increases in presence of NADH (By similarity). Interacts with processed form of PARP1 (Poly [ADP-ribose] polymerase 1, processed C-terminus); interaction is mediated with poly-ADP-ribose chains attached to PARP1, promoting translocation into the nucleus (By similarity).|||Nucleus|||Ubiquitination by XIAP/BIRC4 does not lead to proteasomal degradation. Ubiquitination at Lys-254 by XIAP/BIRC4 blocks its ability to bind DNA and induce chromatin degradation, thereby inhibiting its ability to induce cell death.|||Under normal conditions, a 54-residue N-terminal segment is first proteolytically removed during or just after translocation into the mitochondrial intermembrane space (IMS) by the mitochondrial processing peptidase (MPP) to form the inner-membrane-anchored mature form (AIFmit). During apoptosis, it is further proteolytically processed at amino-acid position 101 leading to the generation of the mature form, which is confined to the mitochondrial IMS in a soluble form (AIFsol). AIFsol is released to the cytoplasm in response to specific death signals, and translocated to the nucleus, where it induces nuclear apoptosis in a caspase-independent manner.|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Tek ^@ http://purl.uniprot.org/uniprot/B1AWS8|||http://purl.uniprot.org/uniprot/Q02858|||http://purl.uniprot.org/uniprot/Q80YS4 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-990 on the kinase activation loop.|||Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner, where Tyr-990 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1106 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2 (By similarity). Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1100 is important for interaction with GRB2 and GRB7. Phosphorylation at Tyr-1106 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.|||Cell junction|||Cell membrane|||Embryonically lethal. Embryos die at about 10 dpc, due to strongly decreased numbers of blood vessel endothelial cells, leading to severe hemorrhaging, and due to defects in heart trabeculae development. Mice display a general malformation of the vascular network with defective sprouting and dilated blood vessels. Conditional by inversion allele knockout mice don't have Schlemm's canal. Haploinsufficient mice developed a severely hypomorphic Schlemm's canal with convolutions and focal narrowing (PubMed:27270174).|||Expression detectable in day 8.5 embryos.|||Homodimer. Heterodimer with TIE1. Interacts with ANGPT1, ANGPT2 and ANGPT4. At cell-cell contacts in quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. In the absence of endothelial cell-cell contacts, interaction with ANGPT1 mediates contacts with the extracellular matrix. Interacts (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain) (By similarity). Interacts with PTPRB; this promotes endothelial cell-cell adhesion. Interacts with DOK2, GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at contacts with the extracellular matrix in migrating cells.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2).|||Secreted|||Specifically expressed in developing vascular endothelial cells. Abundantly expressed in lung and heart, moderately in brain, liver and kidney, and weakly in thymus, spleen and testis.|||The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins.|||Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1, SHC1 and TIE1.|||Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation (By similarity).|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Neu2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J224|||http://purl.uniprot.org/uniprot/E9Q0I0|||http://purl.uniprot.org/uniprot/Q0VGI4|||http://purl.uniprot.org/uniprot/Q3ULV6|||http://purl.uniprot.org/uniprot/Q9JMH3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 33 family.|||Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides (PubMed:10713120). Recognizes sialyl linkage positions of the glycan moiety as well as the supramolecular organization of the sialoglycoconjugate (By similarity). Displays preference for alpha-(2->3)-sialylated GD1a and GT1B gangliosides over alpha-(2->8)-sialylated GD1b, in both monomeric forms and micelles (PubMed:10713120). Hydrolyzes exclusively monomeric GM1 ganglioside, but has no activity toward the miscellar form (By similarity). Has lower sialidase activity for glycoproteins such as fetuin and TF/transferrin that carry a mixture of alpha-(2->3) and alpha-(2->6)-sialyl linkages (By similarity). Cleaves milk oligosaccharide alpha-(2->3)-sialyllactose, but is inactive toward isomer alpha-(2->6)-sialyllactose isomer. Has no activity toward colominic acid, a homomer of alpha-(2->8)-linked Neu5Ac residues (By similarity).|||Highly expressed in heart.|||cytosol http://togogenome.org/gene/10090:Itpk1 ^@ http://purl.uniprot.org/uniprot/Q8BYN3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit ^@ Acetylation by EP300 and CREBBP destabilizes ITPK1, and down-regulates enzymatic activity. Deacetylated by SIRT1.|||Belongs to the ITPK1 family.|||Binds 2 magnesium ions per subunit.|||Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain. Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis.|||Monomer. Interacts with GPS1/COPS1. http://togogenome.org/gene/10090:Or10u4 ^@ http://purl.uniprot.org/uniprot/K7N727 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ap4b1 ^@ http://purl.uniprot.org/uniprot/B0V3P4|||http://purl.uniprot.org/uniprot/Q7TND3|||http://purl.uniprot.org/uniprot/Q9D8S2|||http://purl.uniprot.org/uniprot/Q9WV76 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1). Interacts with TEPSIN; this interaction requires the presence of a functional AP-4 complex (By similarity). Interacts with GRIA2; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons (PubMed:18341993).|||Belongs to the adaptor complexes large subunit family.|||Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways. AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system (By similarity). It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons (PubMed:18341993). AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (By similarity).|||Mice lacking Ap4b1 are fertile, have no overt anatomical abnormalities and have normal life spans. They only show a significantly poorer rotorod performance than wild-type mice. No significant differences in body weight or grip power is observed compared to wild-type mice. The cerebella has normal foliation and a normal laminated cortical structure. Main neuronal types are present in the cerebella and the gross morphology of the soma and dendrites of Purkinje cells is normal.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Tmx3 ^@ http://purl.uniprot.org/uniprot/Q8BXZ1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein disulfide isomerase family.|||Endoplasmic reticulum membrane|||N-glycosylated.|||Probable disulfide isomerase, which participates in the folding of proteins containing disulfide bonds. May act as a dithiol oxidase (By similarity).|||The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins. http://togogenome.org/gene/10090:Rnf5 ^@ http://purl.uniprot.org/uniprot/O35445 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNF5 family.|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with PXN (By similarity). Interacts with JKAMP (PubMed:16166642). Interacts with STING1; the interaction of endogenous proteins is dependent on viral infection (By similarity).|||Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins (PubMed:23093945). May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4 (By similarity). Mediates ubiquitination of PXN/paxillin,thereby regulating cell motility and localization of PXN/paxillin (By similarity). Mediates the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD; the ubiquitination appears to involve E2 ubiquitin-conjugating enzyme UBE2N (By similarity). Mediates the 'Lys-48'-linked polyubiquitination of STING1 at 'Lys-150' leading to its proteasomal degradation; the ubiquitination occurs in mitochondria after viral transfection and regulates antiviral responses (By similarity). Catalyzes ubiquitination and subsequent degradation of ATG4B, thereby inhibiting autophagy (PubMed:23093945).|||Mice are more resistant to lethal infections by group A Streptococcus due to increased autophagy (PubMed:23093945). Macrophages show increased autophagosomes and more efficient bacterial clearance (PubMed:23093945).|||Mitochondrion membrane http://togogenome.org/gene/10090:Zfp277 ^@ http://purl.uniprot.org/uniprot/E9Q6D6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZNF277 family.|||Chromosome|||Cytoplasm|||Down-regulated by oxidative stress.|||Interacts (via zinc-finger domains) with RPS2/40S ribosomal protein S2, perhaps as nascent RPS2 is synthesized during translation; the interaction is direct; the interaction is extra-ribosomal. Interaction with RPS2 competes with the binding of RPS2 to protein arginine methyltransferase PRMT3 (By similarity). Interacts with Polycomb group (PcG) complex protein BMI1 (PubMed:20808772). May be part of a complex including at least ZNF277, BMI1 and RNF2/RING2 (PubMed:20808772).|||Nucleus|||Probable transcription factor (PubMed:20808772). Involved in modulation of cellular senescence; represses transcription of the tumor suppressor gene INK4A/ARF, perhaps acting via the Polycomb group (PcG) complex PRC1 (PubMed:20808772).|||nucleolus http://togogenome.org/gene/10090:Cog4 ^@ http://purl.uniprot.org/uniprot/Q7TSQ9|||http://purl.uniprot.org/uniprot/Q8R1U1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the COG4 family.|||Golgi apparatus membrane|||Monomer. Component of the conserved oligomeric Golgi (COG) complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Mediates interaction of SCFD1 with the COG complex. Interacts with STX5.|||Required for normal Golgi function. Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1.|||cytosol http://togogenome.org/gene/10090:Peg12 ^@ http://purl.uniprot.org/uniprot/Q9WVA7 ^@ Similarity ^@ Belongs to the GSK-3-binding protein family. http://togogenome.org/gene/10090:Tmem214 ^@ http://purl.uniprot.org/uniprot/Q8BM55 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM214 family.|||Constitutively interacts with CASP4; required for the localization of procaspase 4 to the ER.|||Critical mediator, in cooperation with CASP4, of endoplasmic reticulum-stress induced apoptosis. Required or the activation of CASP4 following endoplasmic reticulum stress (By similarity).|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Lox ^@ http://purl.uniprot.org/uniprot/P28301|||http://purl.uniprot.org/uniprot/Q3TP83|||http://purl.uniprot.org/uniprot/Q3TXH3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lysyl oxidase family.|||Contains 1 lysine tyrosylquinone.|||Expressed in aorta (at protein level). Expressed in embryonic, juvenil and adult aorta.|||Interacts with MFAP4.|||Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).|||Proteolytically cleaved by BMP1 which removes the propeptide (PubMed:20181949). Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream of the BMP1 cleavage site (By similarity). The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin (PubMed:16251195). Cleavage by BMP1 to remove the propeptide does not increase enzymatic activity but increases binding to collagen (By similarity). Cleavage by ADAMTS2 produces a form with reduced collagen-binding activity (By similarity).|||Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture (PubMed:27432961).|||Secreted|||Sulfated at Tyr-181 and also at either Tyr-177 or Tyr-178 which enhances binding to collagen.|||The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.|||extracellular space http://togogenome.org/gene/10090:Ajm1 ^@ http://purl.uniprot.org/uniprot/A2AJA9 ^@ Function|||Subcellular Location Annotation ^@ Apical cell membrane|||May be involved in the control of adherens junction integrity.|||adherens junction|||cilium http://togogenome.org/gene/10090:Ptpn6 ^@ http://purl.uniprot.org/uniprot/P29351|||http://purl.uniprot.org/uniprot/Q3UB72|||http://purl.uniprot.org/uniprot/Q3UCJ0 ^@ Disease Annotation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.|||Cytoplasm|||Defects in Ptpn6 are the cause of the motheaten (me) or viable motheaten (mev) phenotypes. Mice homozygous for the recessive allelic mutations develop severe defects in hematopoiesis.|||Expressed predominantly in hematopoietic cells.|||Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. Enhances the inhibition of mast cell activation mediated by the Lilrb4a receptor (PubMed:10026201). The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis.|||Monomer. Interacts with MTUS1 (By similarity). Interacts with MILR1 (tyrosine-phosphorylated) (PubMed:20526344). Interacts with KIT (PubMed:9528781). Interacts with SIRPA/PTPNS1 (PubMed:9712903). Interacts with FCRL2 and FCRL4 (By similarity). Interacts with CD84 (By similarity). Interacts with CD300LF (PubMed:14662855). Interacts with CDK2 (By similarity). Interacts with KIR2DL1; the interaction is enhanced by ARRB2 (By similarity). Interacts (via SH2 1 domain) with ROS1; the interaction is direct and promotes ROS1 dephosphorylation (By similarity). Interacts with EGFR; inhibits EGFR-dependent activation of MAPK/ERK (By similarity). Interacts with LYN (By similarity). Interacts with the tyrosine phosphorylated form of PDPK1 (By similarity). Interacts with CEACAM1 (via cytoplasmic domain); this interaction depends on the monomer/dimer equilibrium and is phosphorylation-dependent (PubMed:19948503, PubMed:9867848). Interacts with MPIG6B (via ITIM motif) (PubMed:23112346). Interacts with KLRI1 and KLRI2 (By similarity). Interacts with moesin/MSN. Interacts with Lilrb4a (when tyrosine phosphorylated); the interaction enhances Lilrb4a-mediated inhibition of mast cell activation (PubMed:10026201, PubMed:9973385). Interacts with CLEC12B (via ITIM motif).|||Nucleus|||Phosphorylated on tyrosine residues. Phosphorylation at Tyr-564 enhances phosphatase activity (By similarity). Binding of KITLG/SCF to KIT increases tyrosine phosphorylation.|||The N-terminal SH2 domain functions as an auto-inhibitory domain, blocking the catalytic domain in the ligand-free close conformation. http://togogenome.org/gene/10090:Tbp ^@ http://purl.uniprot.org/uniprot/P29037|||http://purl.uniprot.org/uniprot/Q6RI65 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBP family.|||Binds DNA as monomer. Belongs to the TFIID complex together with the TBP-associated factors (TAFs). Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (By similarity). Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Association of TBP to form either TFIID or SL1/TIF-IB appears to be mutually exclusive. Interacts with TAF1A, TAF1B and TAF1C (PubMed:9050847). Interacts with TFIIB, NCOA6, DRAP1, DR1 and ELF3. Interacts with SPIB, SNAPC1, SNAPC2 and SNAPC4 (By similarity). Interacts with UTF1 (PubMed:9524124). Interacts with BRF2; this interaction promotes recruitment of BRF2 to TATA box-containing promoters. Interacts with UBTF (By similarity). Interacts with GPBP1 (PubMed:14612417). Interacts with CITED2 (PubMed:10593900). Interacts with ATF7IP (Probable). Interacts with LLPH (PubMed:26961175). Interacts with HSF1 (via transactivation domain) (By similarity). Interacts with GTF2B (via C-terminus); this interaction with promoter-bound TBP guides RNA polymerase II into the pre-initiation complex (PIC) (By similarity). Interacts with PAX5 (By similarity). Interacts with MSX1; the interaction may inhibit MSX1 autoinactivation (PubMed:10215616). Interacts with MSX3 (PubMed:10215616).|||General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Component of a BRF2-containing transcription factor complex that regulates transcription mediated by RNA polymerase III. Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1 with the rDNA promoter. SL1 is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA.|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Nsa2 ^@ http://purl.uniprot.org/uniprot/Q9CR47 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS8 family. Ribosome biogenesis protein NSA2 subfamily.|||Component of the pre-66S ribosomal particle.|||Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles (By similarity).|||nucleolus http://togogenome.org/gene/10090:Zfp260 ^@ http://purl.uniprot.org/uniprot/Q62513 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, it is predominantly detected in cardiomyocyte nuclei This expression is maintained throughout embryonic development in the atria and in the ventricular walls and trabeculae. Also present in the outflow tract, the truncus arteriosus, the developing atrioventricular valve and the cushion mesenchyme. Appears to decrease after 14 dpc and by 17.5 dpc; it is then spatially redistributed, with highest levels in subendocardial myocytes and the septum and no expression in epicardial and apical myocytes. It is also strongly expressed in the atrioventricular valve. During postnatal development, it decreases in both atria and ventricles. In the adult heart, expression is found in the aortic valve in scattered cells and in the atria, ventricles, and septum. Interestingly, it is markedly up-regulated in hypertrophied adult ventricles of transgenic mice overexpressing the angiotensin II receptor (at protein level).|||Belongs to the krueppel C2H2-type zinc-finger protein family.|||Binds DNA. Interacts with GATA4 (By similarity).|||Nucleus|||Predominantly present in heart. Outside the heart, it is detected in embryonic and postnatal vascular smooth muscle cells and in epithelial cells of the lung, gut and kidney at sites of epithelial morphogenesis and in the spinal cord (at protein level).|||Transcription factor that acts as a cardiac regulator and an effector of alpha1-adrenergic signaling. Binds to PE response elements (PERE) present in the promoter of genes such as ANF/NPPA and acts as a direct transcriptional activator of NPPA. Also acts as a cofactor with GATA4, a key cardiac regulator. http://togogenome.org/gene/10090:Oca2 ^@ http://purl.uniprot.org/uniprot/Q62052 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CitM (TC 2.A.11) transporter family.|||Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation. One of the components of the mammalian pigmentary system (By similarity). May serve as a key control point at which color variation is determined. Major determinant of eye color (Probable). Seems to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis (PubMed:12058062).|||Defects in Oca2 are a cause of hypopigmentation of the eyes, skin, and fur. The protein is missing or altered in six independent mutant alleles of the OCA2 locus, suggesting that disruption of this gene results in hypopigmentation phenotype that defines mutant OCA2 alleles.|||Melanosome membrane|||Most abundant in melanocytes. Also present in neonatal and adult eye tissue presumably as a result of expression in the retinal pigmented epithelium and choroid body, known sites of melanogenesis in the eye. Small but detectable amounts also observed in fetal, neonatal and adult brain. Moderate amounts detected in adult testis and ovary. Not detected in heart, kidney, spleen, liver or thymus. http://togogenome.org/gene/10090:Ptprc ^@ http://purl.uniprot.org/uniprot/P06800 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 1/6 subfamily.|||Cell membrane|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Expression is restricted to the hematopoietic compartment of development.|||Heavily N- and O-glycosylated.|||Interacts with SKAP1. Interacts with DPP4; the interaction is enhanced in an interleukin-12-dependent manner in activated lymphocytes (By similarity). Binds GANAB and PRKCSH.|||It is uncertain whether Met-1 or Met-3 is the initiator.|||Membrane raft|||Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN (By similarity). Dephosphorylates LYN, and thereby modulates LYN activity.|||The first PTPase domain interacts with SKAP1. http://togogenome.org/gene/10090:Impdh2 ^@ http://purl.uniprot.org/uniprot/P24547|||http://purl.uniprot.org/uniprot/Q3UAT9 ^@ Activity Regulation|||Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylated by CLOCK in a circadian manner.|||Belongs to the IMPDH/GMPR family.|||Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.|||Cytoplasm|||Homotetramer.|||Homotetramer. Interacts with CLOCK; in a circadian manner. Interacts with ANKRD9; leading to its ubiquitination and degradation by the proteasome.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.|||Nucleus|||Ubiquitinated leading to its degradation by the proteasome.|||cytosol http://togogenome.org/gene/10090:Radx ^@ http://purl.uniprot.org/uniprot/Q8C779 ^@ Function|||Subcellular Location Annotation ^@ Chromosome|||Single-stranded DNA-binding protein recruited to replication forks to maintain genome stability. Prevents fork collapse by antagonizing the accumulation of RAD51 at forks to ensure the proper balance of fork remodeling and protection without interfering with the capacity of cells to complete homologous recombination of double-strand breaks. http://togogenome.org/gene/10090:Srp19 ^@ http://purl.uniprot.org/uniprot/G5E8T3|||http://purl.uniprot.org/uniprot/Q9D104 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SRP19 family.|||Cytoplasm http://togogenome.org/gene/10090:Or8c11 ^@ http://purl.uniprot.org/uniprot/E9Q891 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Defa22 ^@ http://purl.uniprot.org/uniprot/Q8C1N8|||http://purl.uniprot.org/uniprot/W4VSN6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Tlx2 ^@ http://purl.uniprot.org/uniprot/Q61663 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Detected in cranial ganglia at 9 dpc, and in dorsal root ganglia by 10.5 dpc. First detected in gut at 11.5 dpc, with a marked increase by 12.5 dpc. After birth, detected in myenteric and submucosal neurons innervating the distal ileum, colon and rectum.|||Mice are born at the expected Mendelian ratio and show no visible phenotype at birth. After weaning, about 43% of the mice exhibit distended abdomens and growth retardation, the others remain symptomless. About 36% of the mice die between 3 and 6 weeks after birth. Affected mice display distended proximal colons and cecums. Both affected and asymptotic mice have increased numbers of myenteric neurons in ganglia in the proximal and distal colon with a concomitant increase in myenteric ganglion size. In the urinary system, mice exhibit increased numbers of NADPH diaphorase positive neuronal cells in the vesical ganglia, and concomitant vesicourethral sphincter muscle dysfunction.|||Nucleus|||Transcription activator that binds DNA elements with the consensus sequence 5'-CGGTAATTGG-3'. Binds DNA via its homeobox. Required for normal cell death of enteric neurons in the gastrointestinal tract. Required for normal development of the enteric nervous system, and for proper development of normal motility of the gastrointestinal tract.|||Was originally thought to be the ortholog of human HOX11. http://togogenome.org/gene/10090:Krt82 ^@ http://purl.uniprot.org/uniprot/Q99M74 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Or8b101 ^@ http://purl.uniprot.org/uniprot/Q9EQA5 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Bpifa5 ^@ http://purl.uniprot.org/uniprot/Q9CQX3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the BPI/LBP/Plunc superfamily. Plunc family.|||Expressed in interpapillar epithelium of the anterior part of the tongue.|||Expressed in juvenile and adult mice from postnatal day 2.|||May play a role in innate immunity in the oral cavity.|||Secreted http://togogenome.org/gene/10090:Birc2 ^@ http://purl.uniprot.org/uniprot/Q62210 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.|||Belongs to the IAP family.|||Cytoplasm|||Expressed in heart, brain, spleen, lung, liver, skeletal muscle, kidney and testis.|||Interacts with DIABLO/SMAC and with PRSS25; these interactions inhibit apoptotic suppressor activity. Interacts with CASP9. Interacts (via BIR domains) with TRAF2; the interaction is required for IKBKE ubiquitination. Interacts with E2F1, RIPK1, RIPK2, RIPK3, RIPK4, BIRC5/survivin and USP19 (By similarity). Interacts with HSP90AB1 (By similarity). Interacts with several death receptors, inclusing FAS, TNFRSF10A and TNFRSF10B (By similarity). Recruited to TNFRSF10B in the absence of receptor stimulation. When TNFRSF10B is stimulated, further recruited to the receptor and cleaved by caspases. Proteolytic fragments remain associated with TNFRSF10B (By similarity).|||Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.|||Nucleus|||The BIR domains mediate nuclear localization.|||The CARD domain inhibits the activation of E3 ubiquitin ligase activity by preventing RING domain dimerization and E2 ubiquitin donor binding and activation. The CARD domain-mediated autoinhibition of the E3 ubiquitin-protein ligase activity suppresses cell proliferation and migration. USP19 regulates the stability of BIRC2/c-IAP1 by preventing its ubiquitination (By similarity).|||The CARD domain is necessary to stabilize the protein and inhibit the activation of E3 ubiquitin-protein ligase activity of BIRC2/c-IAP1 by preventing RING domain dimerization and E2 ubiquitin donor binding and activation.|||Upon stimulation of death receptors, including TNFRSF10B, recruited to receptors and cleaved by caspases. Proteolytic fragments remain associated with the receptors. This cleavage presumably inactivates the protein. http://togogenome.org/gene/10090:Srsf5 ^@ http://purl.uniprot.org/uniprot/O35326 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Extensively phosphorylated on serine residues in the RS domain.|||Found in a pre-mRNA splicing complex with SRSF4/SFRS4, SRSF5/SFRS5, SNRNP70, SNRPA1, SRRM1 and SRRM2 (By similarity). Interacts (via RS domain) with PHF5A (via N-terminus).|||May be required for progression through G1 and entry into S phase of cell growth. May play a regulatory role in pre-mRNA splicing. Autoregulates its own expression. Plays a role in constitutive splicing and can modulate the selection of alternative splice sites (By similarity).|||Nucleus http://togogenome.org/gene/10090:Tspan31 ^@ http://purl.uniprot.org/uniprot/Q9CQ88 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the tetraspanin (TM4SF) family.|||Membrane http://togogenome.org/gene/10090:Gfpt1 ^@ http://purl.uniprot.org/uniprot/P47856 ^@ Function|||Induction|||Subunit|||Tissue Specificity ^@ Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (PubMed:23395176). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (By similarity).|||Expression in the liver oscillates in an ultradian manner (with a 12 hour period/cycle).|||Homotetramer, may also exist as homodimers.|||Isoform 1 is predominantly expressed in hindlimb muscle and is also expressed weakly in the heart. Seems to be selectively expressed in striated muscle. http://togogenome.org/gene/10090:Dcp2 ^@ http://purl.uniprot.org/uniprot/Q3U671|||http://purl.uniprot.org/uniprot/Q9CYC6 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. DCP2 subfamily.|||Decapping metalloenzyme that catalyzes the cleavage of the cap structure on mRNAs (PubMed:21070968). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:21070968). Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (By similarity). Plays a role in replication-dependent histone mRNA degradation. Has higher activity towards mRNAs that lack a poly(A) tail (PubMed:21070968). Has no activity towards a cap structure lacking an RNA moiety (PubMed:21070968). The presence of a N(6)-methyladenosine methylation at the second transcribed position of mRNAs (N(6),2'-O-dimethyladenosine cap; m6A(m)) provides resistance to DCP2-mediated decapping (By similarity). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (By similarity).|||Found in a mRNA decay complex with LSM1, LSM3, LSM4, EXOSC2, EXOSC4, EXOSC10, PARN, XRN1, CNOT6, UPF1, UPF2 and UPF3B. Forms a complex with DCP1A, EDC3, DDX6 and EDC4/HEDLS, within this complex directly interacts with EDC4/HEDLS. Interacts with DPC1B, UPF1, UPF2 and UPF3B. Associates with polysomes. Interacts (via N-terminus and C-terminus) with TRIM21 (via N-terminus and C-terminus). Interacts with LIMD1, WTIP and AJUBA. Interacts with DDX17 in an RNA-dependent manner. Interacts with ZC3HAV1. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with ZFP36L1 (via N-terminus). Interacts with NBDY.|||Mn(2+) ion is required for highest activity. Can also utilize magnesium ions.|||Nucleus|||P-body|||Strongly expressed in brain and testis. Weakly expressed in lung. Not detected in heart, liver, kidney and muscle (at protein level).|||Strongly expressed in brain, heart, liver at 14.5 and 16.5 dpc. Strongly expressed in brain at 20 dpc. Weakly expressed in heart and liver at 20 dpc (at protein level). http://togogenome.org/gene/10090:Bco1 ^@ http://purl.uniprot.org/uniprot/E9Q321|||http://purl.uniprot.org/uniprot/Q05AC0|||http://purl.uniprot.org/uniprot/Q9JJS6 ^@ Cofactor|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundantly expressed at embryonic day 7 with lower levels at embryonic days 11, 13 and 15.|||Belongs to the carotenoid oxygenase family.|||Binds 1 Fe(2+) ion per subunit.|||Expressed in liver, kidney, small intestine and testis.|||Symmetrically cleaves beta-carotene into two molecules of retinal using a dioxygenase mechanism.|||cytosol http://togogenome.org/gene/10090:Cideb ^@ http://purl.uniprot.org/uniprot/O70303 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CIDE family.|||COPI-coated vesicle|||Endoplasmic reticulum membrane|||Golgi apparatus|||Highly enriched in the liver.|||Interacts with DFFA (By similarity). Interacts with DFFB; inhibited by DFFB (By similarity). Interacts with APOB (PubMed:19187774, PubMed:23297397). Interacts with PREB/SEC12; facilitating loading of SCAP-SREBP into COPII vesicles (PubMed:30858281).|||Lipid droplet|||Lipid transferase specifically expressed in hepatocytes, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion (PubMed:26733203). Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage (PubMed:26733203). Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by promoting directional net neutral lipid transfer from the smaller to larger lipid droplets (By similarity). The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair (By similarity). Promotes lipid exchange and lipid droplet fusion in both small and large lipid droplet-containing hepatocytes (PubMed:26733203). In addition to its role in lipid droplet fusion, also involved in cytoplasmic vesicle biogenesis and transport (PubMed:19187774, PubMed:23297397, PubMed:30858281). Required for very-low-density lipoprotein (VLDL) lipidation and maturation (PubMed:19187774, PubMed:23297397). Probably involved in the biogenesis of VLDL transport vesicles by forming a COPII vesicle coat and facilitating the formation of endoplasmic reticulum-derived large vesicles (PubMed:23297397). Also involved in sterol-regulated export of the SCAP-SREBP complex, composed of SCAP, SREBF1/SREBP1 and SREBF2/SREBP2, by promoting loading of SCAP-SREBP into COPII vesicles (PubMed:30858281). May also activate apoptosis (PubMed:9564035).|||Mice display lower levels of plasma triglycerides and free fatty acids and show smaller lipid droplets in hepatocytes (PubMed:17646209, PubMed:19187774). Mice are resistant to high-fat diet-induced obesity and are protected against hepatic steatosis (PubMed:17646209). Mice also show decreased very-low-density lipoprotein (VLDL)-triacylglycerol secretion and reduced VLDL size (PubMed:19187774). http://togogenome.org/gene/10090:Ly6f ^@ http://purl.uniprot.org/uniprot/P35460 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Rpl19 ^@ http://purl.uniprot.org/uniprot/A2A547|||http://purl.uniprot.org/uniprot/P84099|||http://purl.uniprot.org/uniprot/Q5I0T8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL19 family.|||Citrullinated by PADI4.|||Component of the large ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592).|||Component of the large ribosomal subunit.|||Cytoplasm http://togogenome.org/gene/10090:Ugt8a ^@ http://purl.uniprot.org/uniprot/Q64676 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system. Galactosylates both hydroxy- and non-hydroxy fatty acid-containing ceramides and diglycerides.|||Endoplasmic reticulum|||Membrane http://togogenome.org/gene/10090:Sgsm2 ^@ http://purl.uniprot.org/uniprot/Q80U12 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RUTBC family.|||Cytoplasm|||Interacts with RAB4A, RAB11A, RAP1A, RAP1B, RAP2A and RAP2B. No interaction with RAB27A. Interacts with RAB9A (By similarity).|||Melanosome|||Possesses GTPase activator activity towards RAB32, RAB33B and RAB38. Regulates the trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes by inactivating RAB32 and RAB38. Inhibits RAB32 and RAB38 activation both directly by promoting their GTPase activity and indirectly by disrupting the RAB9A-HPS4 interaction which is required for RAB32/38 activation (PubMed:26620560).|||The Rab-GAP TBC domain possesses GTPase activator activity.|||Widely expressed. http://togogenome.org/gene/10090:Nedd9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J212|||http://purl.uniprot.org/uniprot/O35177 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the CAS family.|||Contains a central domain containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif (By similarity). The SH2-binding sites putatively bind CRKL SH2 domains (By similarity). The HLH motif confers specific interaction with the HLH protein ID2 (By similarity). It is absolutely required for the induction of pseudohyphal growth in yeast and mediates homodimerization and heterodimerization with BCAR1/p130cas (By similarity).|||Cytoplasm|||Expressed in splenic lymphocytes (at protein level) (PubMed:19365570). Expressed in T-cells (at protein level) (PubMed:27359298). Expressed in the thymus (PubMed:16148091). Expressed throughout the brain however particularly abundant in the cortex and hippocampus (PubMed:26683084).|||Golgi apparatus|||Homodimer (By similarity). Forms heterodimers with BCAR1/p130cas (By similarity). Forms complexes with PTK2B/RAFTK, adapter protein CRKL and LYN kinase (By similarity). Part of a complex composed of NEDD9, AURKA and CTTN; within the complex NEDD9 acts as a scaffold protein and is required for complex formation (By similarity). Part of a ternary complex composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4 (via WW domains); the complex mediates ubiquitination and proteasomal degradation of NEDD9/HEF1 (By similarity). Interacts with SMAD3; the interaction promotes NEDD9 ubiquitination and proteasomal degradation (By similarity). Interacts with ID2 (By similarity). Interacts with CTTN (via N-terminus) (PubMed:24574519). Interacts with MICAL (By similarity). Interacts with TXNL4/DIM1 (By similarity). Interacts with BCAR3 (via Ras-GEF domain) (PubMed:12517963, PubMed:19103205). Interacts with SH2D3C isoform 1 and isoform 2 (PubMed:10692442, PubMed:17174122). Interacts with ECT2 (By similarity). Interacts with PTPN11/SHP-2 (via SH2 domains); the interaction is enhanced when NEDD9/CAS-L is tyrosine phosphorylated (By similarity). Interacts (via C-terminus) with PLK1 (via polo box domains) (PubMed:29191835). Interacts with NKX2-5 (By similarity). Interacts with SMAD3; the interaction is inhibited by oxidation of NEDD9 (By similarity). Interacts with NEDD9/HEF1; interaction is induced by CXCL12 promotion of ABL-mediated phosphorylation of NEDD9/HEF1 (By similarity). Interacts (via SH3 domain) with PTK2/FAK (PubMed:25059660). Interacts with FYN; in the presence of PTK2 (By similarity). Interacts with INPPL1/SHIP2 (By similarity).|||Induced by TGF-beta treatment in bone marrow macrophages.|||Knockout mice are morphologically normal and fertile, however take an increased amount of time to learn new spatial memories (PubMed:26683084). Reduced dendritic spine density in the dentate gyrus and both the basal and apical CA1 regions of the hippocampus, with additional decreased in apical dendrite length (PubMed:26683084). The difference in dendritic spine density becomes more pronounced with age (PubMed:26683084). Reduced numbers of osteoclasts in bone marrow macrophages, however overall displayed a normal skeletal phenotype (PubMed:27336669). Abolishes ICAM1 distribution at the pericentral ring of the immunological synapse of T-cells (PubMed:27359298). Impaired movement of T-cell receptor (TCR) microclusters from the synapse periphery to the central region and a decrease in TCR microcluster maturation (PubMed:27359298). Decreased Ca(2+) release from intracellular stores and decreased PLCG1 activation during synapse formation. T-cells failed to form stable immunological synapses, tended to polarize and exhibited uncoordinated, slow migration resulting in significantly smaller synapse area (PubMed:27359298). T-cells show a disorganized cortical actin network, smaller lamellipodial area and undefined lamella boundaries (PubMed:27359298). Decreased splenic follicular and marginal zone B-cells (MZB), however MZB cells were more significantly affected, leading to a decrease in phosphorylcholine-specific IgM and IgG2a (PubMed:16148091). Reduced chemotaxis of T-cells and follicular B-cells in response to CXCL12 and CXCL13 and reduced cell adhesion in response to the integrin ligands VCAM1 and ICAM1 (PubMed:16148091). Decreased number of homing B- and T-cells in the spleen, lymph nodes and peripheral blood, with elevated B-cells in the peripheral blood (PubMed:16148091).|||Nucleus|||PTK2/FAK1 phosphorylates the protein at the YDYVHL motif (conserved among all cas proteins) following integrin stimulation (By similarity). The SRC family kinases (FYN, SRC, LCK and CRK) are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues (By similarity). Ligation of either integrin beta-1 or B-cell antigen receptor on tonsillar B-cells and B-cell lines promotes tyrosine phosphorylation and both integrin and BCR-mediated tyrosine phosphorylation requires an intact actin network (By similarity). Phosphorylation is required to recruit NEDD9 to T-cell receptor microclusters at the periphery of newly formed immunological synapses (PubMed:27359298). In fibroblasts transformation with oncogene v-ABL results in an increase in tyrosine phosphorylation. Transiently phosphorylated following CD3 cross-linking and this phosphorylated form binds to CRKL and C3G (By similarity). A mutant lacking the SH3 domain is phosphorylated upon CD3 cross-linking but not upon integrin beta-1 cross-linking. Tyrosine phosphorylation occurs upon stimulation of the G-protein coupled C1a calcitonin receptor. Calcitonin-stimulated tyrosine phosphorylation is mediated by calcium- and protein kinase C-dependent mechanisms and requires the integrity of the actin cytoskeleton. Phosphorylation at Ser-368 induces proteasomal degradation (By similarity). Phosphorylated by LYN (By similarity). Phosphorylation at Ser-779 by CSNK1D or CSNK1E, or phosphorylation of Thr-803 by CSNK1E enhances the interaction of NEDD9 with PLK1 (By similarity).|||Polyubiquitinated by ITCH/AIP4, leading to proteasomal degradation.|||Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion (By similarity). As a focal adhesion protein, plays a role in embryonic fibroblast migration (PubMed:25059660). May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKl and SHPTP2 to the tyrosine phosphorylated form (By similarity). Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs (PubMed:16148091, PubMed:17174122). Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse (PubMed:27359298). Negatively regulates cilia outgrowth in polarized cysts (By similarity). Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (By similarity). Positively regulates RANKL-induced osteoclastogenesis (PubMed:27336669). Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory (PubMed:26683084).|||cell cortex|||cilium|||cilium basal body|||cytoskeleton|||focal adhesion|||lamellipodium|||spindle pole http://togogenome.org/gene/10090:Hes1 ^@ http://purl.uniprot.org/uniprot/P35428 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed at high levels in undifferentiated neural precursor cells, but the level of expression decreases as neural differentiation proceeds.|||Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).|||Interacts with SIRT1 (By similarity). Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts (via WPRW motif) with TLE1, and more weakly with TLE2. Interacts with HES6. Interacts with an FA complex, composed of FANCA, FANCF, FANCG and FANCL, but not of FANCC, nor FANCE (By similarity).|||Nucleus|||The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.|||The bHLH, as well as cooperation between the central Orange domain and the C-terminal WRPW motif, is required for transcriptional repressor activity.|||Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1 (By similarity). Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity. May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage (By similarity). http://togogenome.org/gene/10090:Or5b106 ^@ http://purl.uniprot.org/uniprot/Q8VFV9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cd109 ^@ http://purl.uniprot.org/uniprot/A6MDD3|||http://purl.uniprot.org/uniprot/Q8R422 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 2 forms of 150 (p150) and 120 kDa (p120) exist due to proteolytic degradation from a 180 kDa form.|||Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.|||Cell membrane|||Heterodimer; disulfide-linked. Interacts with TGFB1 and TGFBR1. Forms a heteromeric complex with TGFBR1, TGFBR2 and TGFBR3 in a ligand-independent manner (By similarity).|||Modulates negatively TGFB1 signaling in keratinocytes.|||N-glycosylated. http://togogenome.org/gene/10090:Igfbp3 ^@ http://purl.uniprot.org/uniprot/P47878|||http://purl.uniprot.org/uniprot/Q3UR87 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. Promotes testicular germ cell apoptosis.|||Interacts with XLKD1. Binds IGF2 more than IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa glycoprotein (ALS). Interacts with TMEM219 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||No effect on baseline apoptosis in the testis but germ cell apoptosis is dramatically reduced following treatment with a gonadotropin-releasing hormone antagonist.|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Gpc6 ^@ http://purl.uniprot.org/uniprot/Q3TP69|||http://purl.uniprot.org/uniprot/Q3V1C9|||http://purl.uniprot.org/uniprot/Q8R3X6|||http://purl.uniprot.org/uniprot/Q9R087 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glypican family.|||Cell membrane|||Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Enhances migration and invasion of cancer cells through WNT5A signaling (By similarity).|||Cell surface proteoglycan.|||Detected from 7 to 17 dpc. Overall expression clearly diminishes after 13 dpc. Mostly expressed in mesoderm-derived tissues, but also present in some neurectoderm-derived sites. High expression limited to mesenchymal tissues. In 11.5 and 13.5 dpc lungs, mostly restricted to the peribronchial mesenchymal cells. In the aorta and other major blood vessels, found in the subendothelial smooth muscle cell layers. Also expressed in the outflow tract of the heart ventricle, but not in other parts of the heart. At 13.5 dpc, in the developing kidney, detected in the metanephric cap mesenchyme of the cortical region, in the condensing mesenchyme surrounding the ureteric branches. Not detected in the adrenal glands. At 11.5 and 13.5 dpc, expressed weakly in the liver septae, but not in the parenchyme. Very strong expression in both the stomach and intestine, in the submucosal layers, in the condensing splanchnic mesenchyme. At 13.5 dpc, expressed in the mesenchymal cells of pancreas, gonad, mesonephric tissue and genital eminence. At 13.5 dpc, expressed in the thymus. At 11.5 dpc, strong expression in the mesenchyme of the mandibular process, with highest expression in the mesenchymal cell layer just below the oral epithelium. Not detected in the overlying epithelium. At 13.5 dpc, highly expressed in the dental mesenchyme surrounding the epithelial bud and near the top of the lip furrow, as well as in the tongue. At 13.5 dpc, expressed in the cartilage primordia of the ear and snout. Highly expressed in intervertebral disks, but not detected in the notochord and vertebrae, both at 11.5 and 13.5 dpc. Highly expressed in mesenchymal condensations of both the forelimb and hindlimb. Overall low expression in the nervous system. At 11.5 dpc, low expression in the neuroepithelium of the hindbrain, the telencephalic vesicle and neuro-epithelial cells lining the mesencephalic vesicle. At 13.5 dpc, detected in the roof of the neopallial cortex, which gives rise to the future cerebral cortex. Weak expression also observed in the medulla oblongata, the choroid plexus, and the ventral mantle layer of the spinal cord. Stronger expression in the ganglia of the glossopharyngeal nerve. At 11.5 and 13.5 dpc, expressed in the mesenchyme surrounding the olfactory epithelium, but not in the epithelium itself. Similarly expressed in the mesenchymal tissues lining the dorsal root ganglia (perineurium), but not in the ganglia. Expression also observed in a few epithelial cells (ectodermal origin), including, at 11.5 dpc, the ventromedial wall of the otic vesicle and, at 13.5 dpc, the cochlea of the inner ear. In the eye, expressed not only in the neural retina but also the cells that compose the wall of the lens vesicle.|||In the cartilage growth-plate, gradient of expression with highest levels from the proliferative and pre-hypertrophic zones to lowest, if any, in the hypertrophic zones (at protein level).|||extracellular space http://togogenome.org/gene/10090:Hoxc5 ^@ http://purl.uniprot.org/uniprot/P32043 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Antp homeobox family.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Ccr7 ^@ http://purl.uniprot.org/uniprot/P47774 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for the MIP-3-beta chemokine. http://togogenome.org/gene/10090:Uba7 ^@ http://purl.uniprot.org/uniprot/Q9DBK7 ^@ Similarity ^@ Belongs to the ubiquitin-activating E1 family. http://togogenome.org/gene/10090:Ubr7 ^@ http://purl.uniprot.org/uniprot/Q8BU04 ^@ Function|||Tissue Specificity ^@ E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation.|||Expressed in testis and sperm (at protein level). http://togogenome.org/gene/10090:Rnf24 ^@ http://purl.uniprot.org/uniprot/Q8BGI1 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Golgi apparatus membrane|||Interacts with TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7.|||May play a role in TRPCs intracellular trafficking. http://togogenome.org/gene/10090:Cchcr1 ^@ http://purl.uniprot.org/uniprot/G3UWS7|||http://purl.uniprot.org/uniprot/Q3TWA2|||http://purl.uniprot.org/uniprot/Q8K2I2 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||May be a regulator of keratinocyte proliferation or differentiation.|||Nucleus http://togogenome.org/gene/10090:Or4d6 ^@ http://purl.uniprot.org/uniprot/Q0VDY1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tor1aip2 ^@ http://purl.uniprot.org/uniprot/Q8BYU6|||http://purl.uniprot.org/uniprot/Q9ER81 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16 dpc, widely expressed with higher expression levels in non-neural cells and hippocampus. In the spinal cord, expressed as early as 12 dpc until p21, the expression levels decrease in the adulthood (at protein level).|||Belongs to the TOR1AIP family.|||Dubious isoform.|||Endoplasmic reticulum membrane|||Expressed in oocytes and preimplantation embryos with expression peaking at the blastocyst stage.|||Expressed in the spinal cord and liver (at protein level).|||Induced by interferon alpha.|||Interacts with TOR1A and TOR1B (ATP-bound).|||Nucleus envelope|||Required for endoplasmic reticulum integrity. Regulates the distribution of TOR1A between the endoplasmic reticulum and the nuclear envelope as well as induces TOR1A, TOR1B and TOR3A ATPase activity (By similarity). http://togogenome.org/gene/10090:Trmt9b ^@ http://purl.uniprot.org/uniprot/Q80WQ4 ^@ Function|||Similarity ^@ Belongs to the methyltransferase superfamily.|||May modify wobble uridines in specific arginine and glutamic acid tRNAs. Acts as a tumor suppressor by promoting the expression of LIN9 (By similarity). http://togogenome.org/gene/10090:Phf19 ^@ http://purl.uniprot.org/uniprot/Q9CXG9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:23160351, PubMed:22438827). Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin. Interacts with SUZ12; competes with AEBP2 for SUZ12 binding. Interacts with EZH2 (via its Tudor domain). Interacts with RIOX1 (By similarity).|||Belongs to the Polycomblike family.|||Nucleus|||Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity (PubMed:23104054, PubMed:23160351, PubMed:22438827, PubMed:23273982). Probably involved in the transition from an active state to a repressed state in embryonic stem cells: acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting H3K36me3 histone demethylases RIOX1 or KDM2B, leading to demethylation of H3K36 and recruitment of the PRC2 complex that mediates H3K27me3 methylation, followed by de novo silencing (PubMed:23160351). Recruits the PRC2 complex to CpG islands and contributes to embryonic stem cell self-renewal (PubMed:22438827). Also binds histone H3 dimethylated at 'Lys-36' (H3K36me2) (By similarity).|||The Tudor domain recognizes and binds H3K36me3. http://togogenome.org/gene/10090:Gprc5b ^@ http://purl.uniprot.org/uniprot/D2DFA9|||http://purl.uniprot.org/uniprot/Q923Z0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 3 family.|||Cell membrane|||Membrane|||Unknown. This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways (By similarity). http://togogenome.org/gene/10090:Abca15 ^@ http://purl.uniprot.org/uniprot/Q6XBG2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Klra3 ^@ http://purl.uniprot.org/uniprot/Q64329 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer; disulfide-linked.|||Membrane|||Receptor on natural killer (NK) cells for class I MHC. http://togogenome.org/gene/10090:Mterf1b ^@ http://purl.uniprot.org/uniprot/A0A096P6K7|||http://purl.uniprot.org/uniprot/B9EJ57 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mTERF family.|||Contains nine structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a left-handed superhelical assembly with a solenoid structure that wraps itself around DNA (By similarity).|||Double knockout of Mterf1a and Mterf1b results in viable animals with no gross phenotype, and normal oxidative phosphorylation capacity. Steady-state mitochondrial DNA levels are normal. There are subtle effects on levels of mitochondrial transcripts: transcripts initiated at the light strand promoter and also situated downstream of the MTERF binding site are increased, levels of 7S RNA are reduced, while levels of other mitochondrial transcripts appear normal.|||Expressed strongly in the heart and at lower levels in brain, liver and kidney.|||Mitochondrion|||Monomer.|||Phosphoprotein with mostly four phosphate groups. While the DNA-binding activity is unaffected by the phosphorylation state, only the phosphorylated form of the protein is active for termination activity. Functioning seems to be regulated by phosphorylation (By similarity).|||Transcription termination factor. Binds to a 28 bp region within the tRNA(Leu(uur)) gene at a position immediately adjacent to and downstream of the 16S rRNA gene; this region comprises a tridecamer sequence critical for directing accurate termination. Binds DNA along the major grove and promotes DNA bending and partial unwinding. Promotes base flipping. Transcription termination activity appears to be polarized with highest specificity for transcripts initiated on the light strand. http://togogenome.org/gene/10090:Sertad4 ^@ http://purl.uniprot.org/uniprot/A7DTG3 ^@ Tissue Specificity ^@ Highly expressed in adult epidermal tissues and in digits. http://togogenome.org/gene/10090:Mmp1b ^@ http://purl.uniprot.org/uniprot/G5E8A9 ^@ Cofactor|||Similarity ^@ Belongs to the peptidase M10A family.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit. http://togogenome.org/gene/10090:Tas2r126 ^@ http://purl.uniprot.org/uniprot/P59532 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor T2R family.|||Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells.|||Membrane|||Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.|||Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity).|||This protein was previously referred to as T2R26 or T2R12 but is now considered to be the ortholog of human TAS2R41. http://togogenome.org/gene/10090:Nlrp6 ^@ http://purl.uniprot.org/uniprot/Q91WS2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as the sensor component of the NLRP6 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to maturation and secretion of IL1B and IL18 (PubMed:21593405, PubMed:30392956, PubMed:32424362, PubMed:34678144). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:30392956). Acts as a recognition receptor (PRR): recognizes and binds specific pathogens and other damage-associated signals, such as lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, or double stranded RNA (dsRNA) (PubMed:26494172, PubMed:30392956, PubMed:34678144). May also recognize and bind lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria; however, LPS is probably not a major activator of the NLRP6 inflammasome (PubMed:34678144). Following LTA- or dsRNA-binding, NLRP6 undergoes liquid-liquid phase separation (LLPS), enhancing multivalent interactions, an essential step for the formation of the NLRP6 inflammasome polymeric complex (PubMed:34678144). The NLRP6 inflammasome acts by promoting recruitment of effector pro-inflammatory caspases (CASP1 and/or CASP4) that catalyze maturation and secretion of IL1B and IL18 in the extracellular milieu (PubMed:30392956). The NLRP6 inflammasome plays a central role in the maintenance of epithelial integrity and host defense against microbial infections in the intestine (PubMed:21565393, PubMed:22763455, PubMed:23696660, PubMed:26638072, PubMed:28445725, PubMed:30392956). Required to restrict infection against Gram-positive bacteria by recognizing lipoteichoic acid (LTA), leading to recruitment of CASP4 and CASP1, and subsequent maturation and secretion of IL1B and IL18 (PubMed:30392956). Involved in intestinal antiviral innate immunity together with DHX15: recognizes and binds viral dsRNA to restrict infection by enteric viruses through the interferon pathway and GSDMD-dependent release of IL18 (PubMed:26494172, PubMed:34678144). Required to prevent infection by the apicomplexan parasite C.tyzzeri in enterocytes by promoting GSDMD-dependent release of IL18 (PubMed:33372132). The NLRP6 inflammasome may also regulate the gut microbiota composition by acting as a sensor of microbiota-associated metabolites to form a PYCARD/ASC-dependent inflammasome for downstream IL18 release and secretion of antimicrobial peptides (PubMed:21565393, PubMed:22763455, PubMed:26638072, PubMed:33617596). Its role in the regulation of the gut microbiota composition is however subject to discussion (PubMed:29281815, PubMed:29281837, PubMed:28801232). Essential for gut mucosal self-renewal and proliferation (PubMed:21593405, PubMed:21543645, PubMed:21565393). Regulate mucus secretion in an inflammasome- and autophagy-dependent manner to prevent invasion by enteric bacteria (PubMed:24581500, PubMed:27339979). During systemic bacterial infections, the NLRP6 inflammasome negatively regulates neutrophil recruitment and neutrophil extracellular traps (NETs) formation (PubMed:22763455, PubMed:30248149, PubMed:33918100, PubMed:33230225). May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (PubMed:26253422).|||Belongs to the NLRP family.|||Cell membrane|||Cytoplasm|||Highly expressed in the gastrointestinal tract, predominantly in colonic myofibroblasts and in colonic epithelial and endothelial cells. Within the intestinal mucosa, highly expressed by goblet cells. Also expressed in hepatocytes and in immune cells, including CD4(+) and CD8(+) T-cells, dendritic cells, mastocytes and peritoneal macrophages, as well as in lung, kidney, bladder and gonads.|||Homomultimer; forms the NLRP6 inflammasome polymeric complex, a filament composed of homopolymers in response to pathogens and other damage-associated signals (PubMed:34678144). The core of NLRP6 inflammasomes consists of a signal sensor component (NLRP6), an adapter (PYCARD/ASC), which recruits effector pro-inflammatory caspases (CASP1 and CASP4) (PubMed:34678144). Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction takes place following NLRP6 activation and formation of liquid-liquid phase separation (LLPS), initiating nucleation which greatly enhances further addition of soluble PYCARD/ASC molecules to the speck in a prion-like polymerization process (PubMed:32424362, PubMed:34678144). Clustered PYCARD/ASC nucleates the formation of CASP1 (or possibly CASP4) filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization (PubMed:34678144). CASP1 filament formation increases local enzyme concentration, resulting in trans-autocleavage and activation (PubMed:34678144). Active CASP1 then processes IL1B and IL18 precursors, leading to the release of mature cytokines in the extracellular milieu and inflammatory response (PubMed:34678144). Interacts with DHX15 (PubMed:26494172).|||Inflammasome|||Knockout mice are born at the expected Mendelian rate with no morphological abnormalities (PubMed:20923861, PubMed:21593405). They are characterized by spontaneous intestinal hyperplasia, inflammatory cell recruitment, exacerbation of chemical colitis induced by exposure to dextran sodium sulfate (DSS) and develop higher tumor loads in response to a combined treatment with the alkylating procarcinogen azoxymethane (AOM) and DSS (PubMed:21593405, PubMed:21543645, PubMed:21565393, PubMed:26638072). The colitogenic phenotype is associated with altered microbiota and is transmissible to cohoused wild-type mice, both early in postnatal life and during adulthood (PubMed:22763455, PubMed:21565393, PubMed:26638072). The effect on microbiota composition is however unclear, since a number of reports do not observe any difference in microbiota composition between wild-type and knockout mice (PubMed:29281815, PubMed:29281837, PubMed:28801232). Mice infected with an enteric pathogen, such as Citrobacter rodentium, show impaired clearance of the bacteria from colon (PubMed:24581500). Their intestinal epithelium lack a thick continuous overlaying inner mucus layer and exhibit a marked goblet cell hyperplasia along with abrogated mucus secretion (PubMed:24581500). When injected intraperitoneally or intravenously, knockout mice show increased resistance to Salmonella typhimurium, Listeria monocytogenes or Escherichia coli (PubMed:22763455). Mice show reduced intestinal antiviral innate immunity and are more susceptible to oral infection with encephalomyocarditis virus (PubMed:26494172). After crushing the sciatic nerve, mutant mice have a more dramatic drop in sciatic function index immediately upon surgery compared to the control group and need more time to recover fully (PubMed:26253422). Mutant animals show reduced systolic blood pressure without affecting heart rate (PubMed:20923861). Males, but not females, exhibit increased urine flow and decreased ability to reduce urinary flow under water restriction conditions compared to wild type littermates (PubMed:20923861). Mutant males may show somewhat lowered cognitive performance (PubMed:20923861).|||Nucleus membrane|||Polyubiquitinated with 'Lys-63'-linked chains, promoting the interaction with PYCARD/ASC and formation of the NLRP6 inflammasome (PubMed:32424362). Deubiquitination by CYLD decreases the interaction with PYCARD/ASC (PubMed:32424362).|||Produced by alternative promoter usage.|||Produced by alternative splicing.|||The poly-Lys disordered region (350-354) mediates the formation of liquid-liquid phase separation (LLPS), an essential step for nucleation and formation of the NLRP6 inflammasome complex.|||The role of the NLRP6 inflammasome in the regulation of the gut microbiota composition is unclear (PubMed:21565393, PubMed:22763455, PubMed:26638072, PubMed:29281815, PubMed:29281837, PubMed:28801232). Some studies suggest that NLRP6 shapes the commensal gut microbiota composition (PubMed:21565393, PubMed:22763455, PubMed:26638072). However, other groups do not observe any difference in microbiota composition between wild-type and knockout mice (PubMed:29281815, PubMed:29281837, PubMed:28801232). Differences observed were attributed to mother and cage covariates rather than Nlrp6 deficiency (PubMed:29281815, PubMed:29281837, PubMed:28801232).|||Up-regulated by rosiglitazone, a PPARG agonist, in CT26 cells. Down-regulated by CRH during water-avoidance stress.|||Up-regulated transiently following sterile or LPS-induced sciatic nerve injury with a peak after 4 hours. http://togogenome.org/gene/10090:Slc28a2 ^@ http://purl.uniprot.org/uniprot/O88627 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Apicolateral cell membrane|||Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.|||Membrane|||Sodium-dependent and purine-selective transporter. Exhibits the transport characteristics of the nucleoside transport system cif or N1 subtype (N1/cif) (selective for purine nucleosides and uridine). Plays a critical role in specific uptake and salvage of purine nucleosides in kidney and other tissues. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (By similarity). http://togogenome.org/gene/10090:Kmt5c ^@ http://purl.uniprot.org/uniprot/Q6Q783 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar4-20 subfamily.|||Chromosome|||Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:15145825, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By similarity). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression (PubMed:15145825). Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions (PubMed:15145825). KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (PubMed:15750587, PubMed:16612004). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273).|||Homodimer (PubMed:24049080). Interacts with HP1 proteins CBX1, CBX3 and CBX5. Interacts with RB1 family proteins RB1, RBL1 and RBL2.|||Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196).|||Nucleus http://togogenome.org/gene/10090:Scd4 ^@ http://purl.uniprot.org/uniprot/Q6T707 ^@ Cofactor|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family.|||Detected in heart, but not in brain, liver, skin or adipose tissue.|||Endoplasmic reticulum membrane|||Expected to bind 2 Fe(2+) ions per subunit.|||Microsome membrane|||Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA (PubMed:12815040, PubMed:16443825). Required for the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides (By similarity).|||The histidine box domains are involved in binding the catalytic metal ions.|||Up-regulated by agonists that activate NR1H3. Up-regulated by a fat-free high-carbohydrate diet. Not down-regulated by a high-carbohydrate diet supplemented with unsaturated fatty acids. Down-regulated by leptin. http://togogenome.org/gene/10090:Neurl1a ^@ http://purl.uniprot.org/uniprot/Q923S6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ According to PubMed:11585928, knockout male mice lacking Neurl1 are sterile due to a defect in axoneme organization in the spermatozoa that leads to compromised tail movement and sperm motility; knockout female mice lacking Neurl1 are defective in the final stages of mammary gland maturation during pregnancy. According to PubMed:11481456 knockout mice lacking Neurl1 are viable and morphologically normal but display an olfactory discrimination and are more sensitive to the effect of ethanol on motor coordination.|||Cell membrane|||Expressed in CA1 pyramidal neurons (at protein level). Expressed throughout the adult forebrain, including the cerebral cortex, amygdala, striatum, and CA1 area of the hippocampus. Expressed in sensory neurons of the olfactory epithelium, the vomeronasal organ, mammary gland and skeletal muscle.|||Expressed in the somites at 8.5 dpc onwards.|||Interacts with CPEB3 (via N-terminal domain); the interaction increases CPEB3 ubiquitination. Interacts with DLL1 (PubMed:19723503).|||Myristoylation is a determinant of membrane targeting.|||Perikaryon|||Plays a role in hippocampal-dependent synaptic plasticity, learning and memory. Involved in the formation of spines and functional synaptic contacts by modulating the translational activity of the cytoplasmic polyadenylation element-binding protein CPEB3. Promotes ubiquitination of CPEB3, and hence induces CPEB3-dependent mRNA translation activation of glutamate receptor GRIA1 and GRIA2. Can function as an E3 ubiquitin-protein ligase to activate monoubiquitination of JAG1 (in vitro), thereby regulating the Notch pathway. Acts as a tumor suppressor; inhibits malignant cell transformation of medulloblastoma (MB) cells by inhibiting the Notch signaling pathway.|||Postsynaptic density|||Up-regulated by synaptic activity.|||dendrite|||perinuclear region http://togogenome.org/gene/10090:Aplnr ^@ http://purl.uniprot.org/uniprot/Q9WV08 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed from embryonic 8 days post-coitum (dpc) throughout the subsequent stages of formation of the cardiovascular system (PubMed:10473142).|||Expressed in coronary endothelial cells (at protein level) (PubMed:28890073). Expressed in the embryo, allantoic and endothelial precursor cells of the yolk sac at 8 days post-coitum (dpc) (PubMed:28663440). Expressed in the secondary heart field and somite at 8.25 dpc (PubMed:28854362). Expressed in fetal allantoic endothelial cells at 9 dpc (PubMed:28663440). Expressed in the allantoid and the invading fetal vasculature of the placenta at 9.5 dpc (PubMed:28854362). Expressed in endothelial cells adjacent to syncytiotrophoblast cells at 10.5 dpc (PubMed:28663440). Expressed weakly in the embryonic heart at 11.5 dpc (PubMed:26611206). Expressed in the adult heart (PubMed:26611206). Expressed in endothelial cells and cardiomyocytes and weakly expressed in fibroblasts (PubMed:10473142, PubMed:26611206).|||Mice lacking APLNR are not represented at Mendelian ratios. Mutant embryos exhibit incomplete penetrance of embryonic lethality (PubMed:28854362, PubMed:28663440). Mutant embryos display improper establishment of the fetal-maternal circulation, such as underdeveloped yolk sac vasculature, embryonic vascular malformations and impaired cardiac tube looping at 10.5 dpc (PubMed:28854362, PubMed:28663440). Mice heart of embryos show reduced coronary vessel growth at 13.5 dpc (PubMed:28890073). The heart of mutant adult mice induced by pressure overload display no improvement in cardiac dysfunction, hypertrophy and fibrosis in response to peptide hormone APELA treatment (PubMed:28371822). Conditional knockout in heart endothelial cells leads to delayed progression of vessel growth onto the heart and reduced branching of the developing coronary plexus in both the subepicardial and intramyocardial layers at 13.5 and 15.5 dpc (PubMed:28890073). Conditional endothelial-specific knockout adult mice, despite severe embryonic coronary vessel defects recover normal cardiac functions; endocardial-derived coronary vessels expand to rescue defective sinus venosus development in a APELA-APLNR-independent manner (PubMed:28890073). Double knockout mice of APLNR and APELA genes exhibited the same penetrance and embryonic lethality as single APELA knockout mice (PubMed:28854362).|||Receptor for apelin receptor early endogenous ligand (APELA) and apelin (APLN) hormones coupled to G proteins that inhibit adenylate cyclase activity. Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a receptor for APELA hormone (PubMed:28854362, PubMed:28890073, PubMed:28663440). May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Promotes sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development (PubMed:28890073). Also plays a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (PubMed:28371822).|||Up-regulated following myocardial infarction (MI) (at protein level) (PubMed:26611206). http://togogenome.org/gene/10090:Epha7 ^@ http://purl.uniprot.org/uniprot/A2BDQ4|||http://purl.uniprot.org/uniprot/Q61772 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.|||Cell membrane|||During visual system development, expressed in an anterior to posterior decreasing gradient stretching through the entire midbrain. This gradient has the reverse orientation to the one defined by the expression of ephrins. Isoform 4 and isoform 5 are expressed at the edges of the embryonic cranial neural fold. In myogenic progenitor cells, highly expressed, at least as early as 11.5 dpc, expression decreases until 4 weeks after birth (PubMed:27446912).|||Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain).|||Membrane|||Mice are viable, fertile and show no gross morphological or behavioral defects. However, topographic targeting errors of nasal and temporal retinal axons appear during development of the retinocollicular projections in the visual system. 10 percent of the embryos also display exencephalic overgrowth of forebrain tissues which might be the result of reduced apoptosis.|||Phosphorylated. Isoform 4 inhibits isoform 1 phosphorylation and may regulate its function in adhesion.|||Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 and MAPK3 which are phosphorylated upon activation of EPHA7. Isoform 4 which lacks the kinase domain may regulate isoform 1 adhesive properties.|||Truncated receptor lacking the kinase domain.|||Widely expressed in embryo. In adult, expression restricted to hippocampus, testis and spleen. Expressed in myogenic progenitor cells (PubMed:27446912). http://togogenome.org/gene/10090:Cyp4a30b ^@ http://purl.uniprot.org/uniprot/A0A087WS15 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Gsdma ^@ http://purl.uniprot.org/uniprot/Q9EST1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage by bacterial SpeB relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A, N-terminal) that initiates pyroptosis.|||Expressed predominantly in the gastrointestinal (GI) tract and in the skin at a lower level. In the GI tract, the expression is highly restricted to the esophagus and forestomach.|||Expression is first detected at 12.5 dpc.|||Homooligomer; homooligomeric ring-shaped pore complex containing 18-36 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.|||Mice are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model (PubMed:35110732). Mice lacking Gsdma, Gsdma2 and Gsdma3 are highly susceptible to subcutaneous group A Streptococcus (GAS) infection in an animal model (PubMed:35545676).|||Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:35110732). Released upon cleavage by bacterial effector protein SpeB, and binds to membrane inner leaflet lipids (PubMed:35110732). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (By similarity). Pyroptosis triggers the elimination of the infected skin cell, depriving the pathogen of its protective niche, while inducing an inflammatory response (PubMed:35110732, PubMed:35545676). This ultimately prevents bacterial penetration of the epithelial barrier and a subsequent systemic dissemination of the pathogen (PubMed:35110732, PubMed:35545676). Binds to cardiolipin and other acidic phospholipids, such as phosphatidylserine, which mediate its targeting to the inner leaflet membrane (By similarity).|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-A, N-terminal) following cleavage by bacterial effector protein SpeB (PubMed:35110732).|||This form constitutes the precursor of the pore-forming protein and acts as a sensor of bacterial infection: upon infection, specifically cleaved by bacterial effector protein SpeB in epithelial cells, releasing the N-terminal moiety (Gasdermin-A, N-terminal) that binds to membranes and forms pores, triggering pyroptosis.|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Cxcl2 ^@ http://purl.uniprot.org/uniprot/P10889|||http://purl.uniprot.org/uniprot/Q3U1J5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the intercrine alpha (chemokine CxC) family.|||Chemotactic for human polymorphonuclear leukocytes but does not induce chemokinesis or an oxidative burst.|||Homotetramer.|||Secreted http://togogenome.org/gene/10090:Smpd4 ^@ http://purl.uniprot.org/uniprot/Q6ZPR5 ^@ Activity Regulation|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by phosphatidylserine and tumor necrosis factor (TNF) (PubMed:25180167). Inhibited by scyphostatin (By similarity).|||Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:25180167). It has a relevant role in the homeostasis of membrane sphingolipids, thereby influencing membrane integrity, and endoplasmic reticulum organization and function. May sensitize cells to DNA damage-induced apoptosis. In skeletal muscle, mediates TNF-stimulated oxidant production (PubMed:25180167).|||Endoplasmic reticulum membrane|||Expressed in skeletal muscle (at protein level).|||Expressed in skeletal muscle but a lower levels than isoform 1 (at protein level).|||Golgi apparatus membrane|||Nucleus envelope|||sarcolemma http://togogenome.org/gene/10090:Rnf222 ^@ http://purl.uniprot.org/uniprot/Q8CEF8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Runx2 ^@ http://purl.uniprot.org/uniprot/E0CZ12|||http://purl.uniprot.org/uniprot/F8WHN7|||http://purl.uniprot.org/uniprot/Q08775 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes and contains the phosphorylation sites.|||Cytoplasm|||Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (PubMed:29148101).|||Expression occurs early during skeletal development and is restricted to cells of the mesenchymal condensations and of the osteoblast lineage at 12.5 dpc.|||Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX.|||Found in thymus and testis, T-cell lines but not in B-cell lines. Isoform 2 is exclusively found in bone, particularly in osteoblasts; isoforms 3 and 4 are expressed in T-cell lines; isoforms 5, 6, 7, 8 and 9 can be found in osteoblasts and osteosarcoma cell lines.|||Heterodimer of an alpha and a beta subunit. The alpha subunit binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Interacts with XRCC6 (Ku70) and XRCC5 (Ku80). Interacts with CCNB1, KAT6A and KAT6B (By similarity). Interacts with HIVEP3. Interacts with IFI204. Interaction with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors. Binds to HIPK3. Interacts with FOXO1 (via a C-terminal region); the interaction inhibits RUNX2 transcriptional activity towards BGLAP. Interacts with FOXP3 (By similarity). Interacts with TMEM119 (PubMed:21239498). Interacts with OLFM2 (By similarity). Interacts with IPO7; the interaction inhibits RUNX2 nuclear translocation in osteoblasts (PubMed:35922041).|||Induced during the early stages of odontoblastic differentiation in dental papilla cells (PubMed:35922041). Induced during osteoblastic differentiation (PubMed:35922041).|||Interacts with DDX5.|||Nucleus|||Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 transactivation during osteoblastic differentiation. Phosphorylation at Ser-537 by CDK1 promotes endothelial cell proliferation required for tumor angiogenesis probably by facilitating cell cycle progression (By similarity).|||Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. Inhibits KAT6B-dependent transcriptional activation (By similarity). In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). http://togogenome.org/gene/10090:1700057G04Rik ^@ http://purl.uniprot.org/uniprot/Q3V0U0 ^@ Function|||Similarity ^@ Belongs to the phospholipid scramblase family.|||May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. http://togogenome.org/gene/10090:Cadm3 ^@ http://purl.uniprot.org/uniprot/Q99N28 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc predominantly expressed in the nervous system.|||Belongs to the nectin family.|||Cell junction|||Cell membrane|||Homodimer. Can form trans-heterodimers with NECTIN3. Interacts with EPB41L1, DLG3, PALS2 and CASK.|||Involved in the cell-cell adhesion. Has both calcium-independent homophilic cell-cell adhesion activity and calcium-independent heterophilic cell-cell adhesion activity with IGSF4, NECTIN1 and NECTIN3. Interaction with EPB41L1 may regulate structure or function of cell-cell junctions.|||Mainly expressed in brain, in neuronal cell bodies of cerebellum, cortex, hippocampus, hypothalamus and spinal cord. In spinal cord predominantly expressed in motor neurons. Expressed in axons, presynaptic nerve terminals, glia cell processes.|||The cytoplasmic region mediates interaction with EPB41L1, DLG3, PALS2 and CASK. http://togogenome.org/gene/10090:Klra17 ^@ http://purl.uniprot.org/uniprot/Q8BJS9|||http://purl.uniprot.org/uniprot/Q9JMA4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cul2 ^@ http://purl.uniprot.org/uniprot/Q9D4H8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cullin family.|||Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and a variable substrate-specific adapter. Component of the ECS(VHL) or CBC(VHL) complex containing VHL. Component of the ECS(MED8) complex with the probable substrate recognition component MED8. Component of multiple ECS complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component (By similarity). Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:33590678). Component of a probable ECS E3 ubiquitin-protein ligase complex containing CUL2, RBX1, ELOB, ELOC and FEM1B. Part of an E3 ubiquitin-protein ligase complex including ZYG11B, CUL2 and Elongin BC. Part of an E3 ubiquitin-protein ligase complex including ZER1, CUL2 and Elongin BC. Interacts with RBX1, RNF7, FEM1B and TIP120A/CAND1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation. Component of VCB (elongins BC/CUL2/VHL) complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation.|||Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. CUL2 may serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (PubMed:33590678).|||Neddylated; which enhances the ubiquitination activity of ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes. CBC(VHL) complex formation seems to promote neddylation (By similarity). Deneddylated via its interaction with the COP9 signalosome (CSN) complex.|||Nucleus http://togogenome.org/gene/10090:Col3a1 ^@ http://purl.uniprot.org/uniprot/P08121 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibrillar collagen family.|||Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of ADGRG1 in the developing brain and binding to ADGRG1 inhibits neuronal migration and activates the RhoA pathway by coupling ADGRG1 to GNA13 and possibly GNA12.|||Expressed in embryonic brain, specifically in the meninges, pial basement membrane and blood vessels (at protein level).|||Neuronal ectopias and abnormal cortical lamination.|||O-linked glycan consists of a Glc-Gal disaccharide bound to the oxygen atom of a post-translationally added hydroxyl group.|||Proline residues at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||Trimers of identical alpha 1(III) chains. The chains are linked to each other by interchain disulfide bonds. Trimers are also cross-linked via hydroxylysines. Interacts with ADGRG1 (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Ncam2 ^@ http://purl.uniprot.org/uniprot/O35136 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Expressed in subsets of both olfactory and vomeronasal neurons in a zone-specific manner.|||May play important roles in selective fasciculation and zone-to-zone projection of the primary olfactory axons. http://togogenome.org/gene/10090:Mgat4e ^@ http://purl.uniprot.org/uniprot/A6H684 ^@ Function ^@ Glycosyltransferase-like protein that may participate in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N-linked glycans. http://togogenome.org/gene/10090:Tmem242 ^@ http://purl.uniprot.org/uniprot/Q8VCR3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM242 family.|||Interacts with the core subunits NDUFAF1, ECSIT and ACAD9 of the MCIA complex. Interacts with ATP5MC3, NDUFC2, TMEM70, MT-ND2 AND MT-ND3.|||Mitochondrion inner membrane|||Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by facilitating the membrane insertion and oligomer formation of the subunit c/ATP5MC3. Participates in the incorporation of the c-ring into vestigial complexes. Additionally influences the incorporation of subunits MT-ATP6, MT-ATP8, ATP5MJ, and ATP5MK in the ATP synthase. http://togogenome.org/gene/10090:Anpep ^@ http://purl.uniprot.org/uniprot/P97449 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines (By similarity). May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells (PubMed:8691132). May have a role in angiogenesis and promote cholesterol crystallization (By similarity). May have a role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 and regulating its activity (PubMed:22677001).|||Cell membrane|||Expressed in the intestinal brush border (at protein level) (PubMed:22677001). Highly expressed in intestinal tract and kidney, present in liver, lymph node, spleen, and brain (PubMed:8805662, PubMed:8103749). Found as well in monocytes, macrophages, dendritic cells, veiled cells and B-cells but not on T-cells and thymocytes (PubMed:8103749).|||Homodimer (By similarity). Interacts with SLC6A19 (PubMed:22677001).|||May undergo proteolysis and give rise to a soluble form.|||N- and O-glycosylated.|||Sulfated. http://togogenome.org/gene/10090:Dnah6 ^@ http://purl.uniprot.org/uniprot/E9Q0B6 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Hoxc13 ^@ http://purl.uniprot.org/uniprot/P50207 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Abd-B homeobox family.|||Expressed in differentiating keratinocytes. In the hair follicle lower matrix, expressed in all 3 hair shaft-forming compartments, i.e. cuticle, cortex and medulla. Expression stops sharply at the boundary with the germinal matrix compartment.|||Nucleus|||Transcription factor which plays a role in hair follicle differentiation. Regulates FOXQ1 expression and that of other hair-specific genes. http://togogenome.org/gene/10090:Rnps1 ^@ http://purl.uniprot.org/uniprot/Q99M28 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Cytoplasm|||Found in mRNA splicing-dependent exon junction complexes (EJC). Found in a post-splicing complex with NXF1, RBM8A, UPF1, UPF2, UPF3A, UPF3B and RNPS1. Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) and PSAP complexes consisting of RNPS1, SAP18 and either ACIN1 or PNN, respectively; the ASAP and PSAP complexes probably are formed mutually exclusive. Component of the active spliceosome. Associates with polysomes. Interacts with the cleaved p110 isoform of CDC2L1, CSNK2A1, PNN, SART3, SRP54, SRRM1 and TRA2B/SFRS10 (By similarity).|||Nucleus|||Nucleus speckle|||Part of pre- and post-splicing multiprotein mRNP complexes. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Enhances the formation of the ATP-dependent A complex of the spliceosome. Involved in both constitutive splicing and, in association with SRP54 and TRA2B/SFRS10, in distinctive modulation of alternative splicing in a substrate-dependent manner. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Participates in mRNA 3'-end cleavage. Involved in UPF2-dependent nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Also mediates increase of mRNA abundance and translational efficiency. Binds spliced mRNA 20-25 nt upstream of exon-exon junctions (By similarity).|||Phosphorylated on one or more of the four Ser/Thr residues (Ser-43, Thr-49, Ser-52 or Ser-53). Ser-53 phosphorylation site is important for splicing and translation stimulation activity in vitro (By similarity).|||The RRM domain is required for the formation of the ASAP complex. http://togogenome.org/gene/10090:Gas2l1 ^@ http://purl.uniprot.org/uniprot/Q8JZP9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GAS2 family.|||Interacts with MAPRE1.|||Seems to be involved in the cross-linking of microtubules and microfilaments (By similarity). Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers (By similarity).|||cytoskeleton|||stress fiber http://togogenome.org/gene/10090:Sctr ^@ http://purl.uniprot.org/uniprot/H7BX37|||http://purl.uniprot.org/uniprot/Q5FWI2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||In brain, expressed in the hippocampal CA1 region, the lower layer of cerebral cortex, the anterior olfactory nuclei, the anterior ventrolateral thalamus, the lateral region of hypothalamus, substantia nigra, tegmental area and central nucleus of the inferior colliculus, the ventral supramamillary nucleus and the cerebellum (PubMed:17008357). Expressed in brown adipocytes: expression predominates in mature brown adipocytes (at protein level) (PubMed:30449620).|||Membrane|||Mice are overtly normal and fertile (PubMed:17008357). Mice however display impaired synaptic plasticity in the hippocampus: the number of dendritic spines in the CA1 hippocampal pyramidal cells is slightly reduced and mice show abnormal social behavior (PubMed:17008357). Mice are not hyperphagic and display normal food intake (PubMed:24769669). Following a 12 week high-fat diet, knockout mice gain significantly less weight and exhibit lower body fat content, possibly caused by reduced fat absorption in the intestine (PubMed:24769669). Mice also show mild polydipsia and polyuria; kidney display altered glomerular and tubular morphology (PubMed:17283064).|||Phosphorylated on Ser and Thr residues at the cytoplasmic C-terminus by G protein-coupled receptor kinases (GRKs).|||Receptor for secretin (SCT), which is involved in different processes such as regulation of the pH of the duodenal content, food intake and water homeostasis (PubMed:20927047, PubMed:24273196, PubMed:30449620). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (PubMed:30449620). Upon binding to secretin, regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas (By similarity). In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation (PubMed:30449620). Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation (PubMed:30449620). Also able to stimulate lipolysis in white adipocytes (PubMed:24273196). Also plays an important role in cellular osmoregulation by regulating renal water reabsorption (PubMed:17283064). Also plays a role in the central nervous system: required for synaptic plasticity (PubMed:17008357). http://togogenome.org/gene/10090:Heg1 ^@ http://purl.uniprot.org/uniprot/A0A338P6D4|||http://purl.uniprot.org/uniprot/E9Q440|||http://purl.uniprot.org/uniprot/Q6DFX1 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Zbtb9 ^@ http://purl.uniprot.org/uniprot/Q8CDC7 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Tma7 ^@ http://purl.uniprot.org/uniprot/Q14A47|||http://purl.uniprot.org/uniprot/Q8K003 ^@ Similarity ^@ Belongs to the TMA7 family. http://togogenome.org/gene/10090:Mup12 ^@ http://purl.uniprot.org/uniprot/P11588|||http://purl.uniprot.org/uniprot/Q58ES8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in the urine of adult male mice but absent from that of females.|||Belongs to the calycin superfamily. Lipocalin family.|||Binds pheromones that are released from drying urine of males. These pheromones affect the sexual behavior of females.|||Secreted http://togogenome.org/gene/10090:Sdc4 ^@ http://purl.uniprot.org/uniprot/O35988|||http://purl.uniprot.org/uniprot/Q3U5S6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the syndecan proteoglycan family.|||Cell surface proteoglycan which regulates exosome biogenesis in concert with SDCBP and PDCD6IP.|||Cell surface proteoglycan.|||Homodimer. Interacts with CDCP1 and SDCBP (By similarity). Interacts (via its cytoplasmic domain) with GIPC (via its PDZ domain). Interacts (via its cytoplasmic domain) with NUDT16L1.|||Membrane|||O-glycosylated; contains both chondroitin sulfate and heparan sulfate. Ser-44, Ser-62 and Ser-64 can all be modified by either chondroitin sulfate or heparan sulfate, and the protein exists in forms that contain only chondroitin sulfate, only heparan sulfate and both chondroitin sulfate and heparan sulfate.|||Secreted|||Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3.|||Ubiquitous. Highest levels in liver, kidney and lung. http://togogenome.org/gene/10090:Tob2 ^@ http://purl.uniprot.org/uniprot/Q543X9|||http://purl.uniprot.org/uniprot/Q9JM55 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Anti-proliferative protein inhibits cell cycle progression from the G0/G1 to S phases.|||Associates with CAF1.|||Belongs to the BTG family.|||Ubiquitous. http://togogenome.org/gene/10090:Tmem71 ^@ http://purl.uniprot.org/uniprot/Q149F5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM71 family.|||Membrane http://togogenome.org/gene/10090:Or5b98 ^@ http://purl.uniprot.org/uniprot/Q8VF19 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gp9 ^@ http://purl.uniprot.org/uniprot/O88186 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Membrane|||The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis. GP-IX may provide for membrane insertion and orientation of GP-Ib (By similarity).|||Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage (By similarity). http://togogenome.org/gene/10090:Trappc6a ^@ http://purl.uniprot.org/uniprot/Q78XR0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAPP small subunits family. BET3 subfamily.|||Endoplasmic reticulum|||May play a role in vesicular transport during the biogenesis of melanosomes.|||Part of the multisubunit transport protein particle (TRAPP) complex. Heterodimer with TRAPPC3 (By similarity). The heterodimer TRAPPC3-TRAPPC6A interacts with TRAPPC2L. Interacts with TRAPPC2L (By similarity).|||Ubiquitous, with lowest expression in skeletal muscle and brain and highest in kidney, liver and testis, as well as in cultured melanocytes.|||cis-Golgi network http://togogenome.org/gene/10090:Gdpd1 ^@ http://purl.uniprot.org/uniprot/Q9CRY7 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycerophosphoryl diester phosphodiesterase family.|||Cytoplasm|||Endoplasmic reticulum|||Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines (PubMed:25528375, PubMed:25596343, PubMed:27637550). Shows a preference for 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF), lysophosphatidylethanolamine (lyso-PE) and lysophosphatidylcholine (lyso-PC) (PubMed:25528375, PubMed:25596343, PubMed:27637550). May be involved in bioactive N-acylethanolamine biosynthesis from both N-acyl-lysoplasmenylethanolamin (N-acyl-lysoPlsEt) and N-acyl-lysophosphatidylethanolamin (N-acyl-lysoPE) (PubMed:25596343, PubMed:27637550). In addition, hydrolyzes glycerophospho-N-acylethanolamine to N-acylethanolamine (PubMed:25596343, PubMed:27637550). Does not display glycerophosphodiester phosphodiesterase activity, since it cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine (PubMed:25528375).|||Lysophospholipase D activity is increased by magnesium and manganese and inhibited by calcium in a concentration dependent manner (By similarity). Loss of lysophospholipase D activity by addition of EDTA (PubMed:25596343).|||Membrane|||Up-regulated in white adipose tissue of obese mice.|||Widely expressed (PubMed:25528375, PubMed:25596343).|||perinuclear region http://togogenome.org/gene/10090:Mier3 ^@ http://purl.uniprot.org/uniprot/Q3UHF3 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Transcriptional repressor. http://togogenome.org/gene/10090:Mpg ^@ http://purl.uniprot.org/uniprot/Q04841 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA glycosylase MPG family.|||Binding to SSBP1 in mitochondria inhibits glycosylase activity in the context of a single-stranded DNA (ssDNA), but not a double-stranded DNA (dsDNA) substrates.|||Binds MBD1. Binds SSBP1.|||Cytoplasm|||Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.|||Nucleus|||mitochondrion nucleoid http://togogenome.org/gene/10090:Cfap410 ^@ http://purl.uniprot.org/uniprot/Q8C6G1 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cilia absent or reduced, virtually no cilia of the normal 5 uM mean length.|||Cytoplasm|||Expressed in the retina.|||Found in a complex with CFAP410, NEK1 and SPATA7 (By similarity). Interacts with NEK1 (By similarity).|||Mitochondrion|||Plays a role in cilia formation and/or maintenance (PubMed:21289087). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Involved in DNA damage repair (By similarity).|||Up-regulated during cartilage differentiation (PubMed:26974433).|||cilium|||cilium basal body|||photoreceptor outer segment http://togogenome.org/gene/10090:Abca17 ^@ http://purl.uniprot.org/uniprot/E9PX95 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCA family.|||Cytoplasm|||Detected in the testis at low levels at postnatal day 5 but increases at postnatal days 20 and 45 (at protein level).|||Endoplasmic reticulum membrane|||In the testis, detected predominantly in elongated spermatids at the late stage of germ cell development and in sperm, with no expression detected in immature germ cells such as spermatogonia and spermatocytes or in somatic cells such as Sertoli cells (at protein level) (PubMed:15810880). Expressed in the head and tail midpiece of elongated spermatids and sperm (at protein level) (PubMed:22237709). Expressed exclusively in the testis (PubMed:15810880, PubMed:22237709).|||N-glycosylated.|||Promotes cholesterol efflux from sperm which renders sperm capable of fertilization (PubMed:22237709). Has also been shown to decrease levels of intracellular esterified neutral lipids including cholesteryl esters, fatty acid esters and triacylglycerols (PubMed:15810880). http://togogenome.org/gene/10090:Peli3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J057|||http://purl.uniprot.org/uniprot/D3Z6V8|||http://purl.uniprot.org/uniprot/Q8BXR6 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the pellino family.|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:23892723). Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6 (By similarity). Mediates 'Lys-63'-linked polyubiquitination of IRAK1. Can activate AP1/JUN and ELK1 (By similarity). Acts as a regulator of innate immunity by mediating 'Lys-63'-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby transforming RIPK2 into a scaffolding protein for downstream effectors, ultimately leading to activation of the NF-kappa-B and MAP kinases signaling (PubMed:23892723). Catalyzes 'Lys-63'-linked polyubiquitination of RIPK2 in parallel of XIAP (PubMed:23892723).|||E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.|||Interacts with TRAF6, MAP3K14 and MAP3K7.|||Mice show impaired clearance of C.rodentium due to decreased NOD2 signaling (PubMed:23892723). Mice display decreased muramyl dipeptide (MDP)-induced expression of cytokines (PubMed:23892723).|||Phosphorylated by IRAK1 enhancing its E3 ligase activity. http://togogenome.org/gene/10090:Isca1 ^@ http://purl.uniprot.org/uniprot/Q9D924 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HesB/IscA family.|||Interacts with CRY2, but not with CRY1 (in vitro).|||Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. Probably involved in the binding of an intermediate of Fe/S cluster assembly.|||Mitochondrion http://togogenome.org/gene/10090:Tm2d1 ^@ http://purl.uniprot.org/uniprot/Q99MB3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TM2 family.|||Interacts with APP beta-APP42 (amyloid-beta protein 42).|||May participate in amyloid-beta-induced apoptosis via its interaction with beta-APP42.|||Membrane|||N-glycosylated. http://togogenome.org/gene/10090:Or52ad1 ^@ http://purl.uniprot.org/uniprot/E9PUN7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cyp2c68 ^@ http://purl.uniprot.org/uniprot/K7N6C2 ^@ Similarity ^@ Belongs to the cytochrome P450 family. http://togogenome.org/gene/10090:Calm4 ^@ http://purl.uniprot.org/uniprot/Q9JM83 ^@ Function ^@ Implicated in the early stage of ectopic ossification. http://togogenome.org/gene/10090:Foxr2 ^@ http://purl.uniprot.org/uniprot/Q3UM89 ^@ Developmental Stage|||Subcellular Location Annotation ^@ Expressed in 9.5 dpc embryo.|||Nucleus http://togogenome.org/gene/10090:Mettl3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J041|||http://purl.uniprot.org/uniprot/Q8C3P7 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MT-A70-like family.|||Cytoplasm|||Embryonic lethality (PubMed:25569111). Blastocysts retain normal morphology and expression of pluripotency markers and yield embryonic stem cells (ESCs) at the expected ratio. However, they fail to adequately terminate their naive state and undergo aberrant and restricted lineage priming at the postimplantation stage, leading to early embryonic lethality (PubMed:25456834, PubMed:25569111). mRNAs show a nearly complete absence of N6-methyladenosine (m6A) methylation (PubMed:25456834, PubMed:25569111). RNAs show defects in splicing and adenosine to inosine editing (PubMed:25569111). Conditional knockout mice lacking Mettl3 in germ cells show male infertility caused by defects in meiosis at the zygotene stage during spermatogenesis (PubMed:28809392). Conditional knockout mice lacking Mettl3 and Mettl14 in germ cells show impaired spermatogenesis (PubMed:28914256). Conditional knockout mice lacking Mettl3 in T-cells show impaired homeostatic expansion of naive T-cells, T-cells remaining in the naive state for up to 12 weeks, thereby preventing colitis (PubMed:28792938). Naive T-cells show loss of m6A modification leading to increased Socs1, Socs3 and Cish mRNA half-life and protein levels, thereby suppressing the IL-7/STAT5 signaling pathway (PubMed:28792938). Conditional knockout mice lacking Mettl3 in the developing nervous system display protracted cell-cycle progression of cortical neural progenitor cells and reduced differentiation of radial glial cells during embryonic cortical neurogenesis (PubMed:28965759).|||Gate loop 1 and gate loop 2 regions are adjacent to the S-adenosyl-L-homocysteine-binding site and display large conformational changes upon ligand-binding. They may play an important role in adenosine recognition. The interface loop contributes to the heterodimer interaction.|||Heterodimer; heterodimerizes with METTL14 to form an antiparallel heterodimer that constitutes an active methyltransferase (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716). Interacts with NCBP1/CBP80 (By similarity). Interacts with EIF4E (By similarity). Interacts with EIF3B (By similarity).|||Methyltransferase activity is regulated by miRNAs via a sequence pairing mechanism (PubMed:25683224). Methyltransferase activity is inhibited by sumoylation (By similarity).|||Nucleus|||Nucleus speckle|||Present in both germ cells and somatic cells during testis development (at protein level) (PubMed:28809392).|||Sumoylation inhibits the N6-adenosine-methyltransferase activity. Sumoylation does not affect subcellular location or interaction with METTL14. Desumoylated by SENP1.|||The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:25456834, PubMed:24394384, PubMed:25569111, PubMed:28809392, PubMed:28792938, PubMed:28869969, PubMed:28965759). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (By similarity). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (By similarity). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (PubMed:25456834, PubMed:24394384, PubMed:25569111). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (PubMed:24209618). M6A also regulates circadian regulation of hepatic lipid metabolism (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (PubMed:28809392, PubMed:28914256, PubMed:32943573). Also required for oogenesis (PubMed:32943573). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (By similarity). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (PubMed:28792938). Inhibits the type I interferon response by mediating m6A methylation of IFNB (By similarity). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (PubMed:28965759). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (By similarity). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (By similarity). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (By similarity).|||While different publications agree on the role of N6-methyladenosine (m6A) on RNA stability and its role in embryonic stem cells (ESCs) pluripotency, the precise function of Mettl3 in ESCs self-renewal is unclear. A first paper reported that Mettl3 promotes self-renewal of ESCs by maintaining the groung state of ESCs (PubMed:24394384). However, opposite conclusions were drawn by publications from other groups (PubMed:25456834, PubMed:25569111). The differences may be explained by different experimental conditions (such as cell types or RNAi off-target effects). http://togogenome.org/gene/10090:Apoh ^@ http://purl.uniprot.org/uniprot/Q01339|||http://purl.uniprot.org/uniprot/Q9CY42 ^@ Caution|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.|||Expressed by the liver and secreted in plasma.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Zfp622 ^@ http://purl.uniprot.org/uniprot/Q91VY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the REI1 family.|||Cytoplasm|||Homo- and heterodimer. Associates with pre-60S ribosomal particles. Interacts with MELK and MYBL2. Interacts with DNAJC21.|||Nucleus|||Phosphorylated by MELK. The phosphorylation may redirect the protein to the nucleus.|||Pre-60S-associated cytoplasmic factor involved in the cytoplasmic maturation of the 60S subunit.|||Ubiquitinated by HECTD1, leading to its degradation. http://togogenome.org/gene/10090:Ackr3 ^@ http://purl.uniprot.org/uniprot/P56485 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels (PubMed:31211835).|||Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.|||Cell membrane|||Early endosome|||Expression detected after 9.5 dpc in the endothelial layer of the forming heart, neural tube, brain and septum transversum. At 10.5 dpc, expressed at high levels in the prosencephalon and in a part of the rhombencephalon and at lower levels in the neural tube, somites and heart. Detected in liver at 11 dpc and 13 dpc, but not at 15 dpc and 17 dpc. During heart development, expression detected mainly in endocardial cells and endocardial cushion mesenchymal cells in both outflow tract and atrioventricular canal regions and to a lesser degree in myocardial cells at 10.5 dpc, in the mesenchyme of the forming valves and in numerous microvessels in the myocardium at 12.5 dpc, and from 14.5 dpc onward mainly in the microvasculature associated with myocardium, valves and great vessels. In developing telencephalon, observed at 11.5 dpc in the ventral telencephalon in proliferative zones of the medial ganglionic eminence (MGE), in ventral part of the lateral ganglionic eminence (LGE) and in Cajal-Retzius (CR) neurons of dorsal telencephalon. At 12.5 dpc, detected in migrating olfactory tubercle neuron precursors and cortical interneurons, and in CR cells and subplate neurons of the cortex. At 13.5 dpc, observed in the germinal zone of MGE in the subpallium, in the marginal zone and cortical subventricular zone (SVZ) of the lateral cortex as well as in pyramidal cells and tangentially migrating interneurons. At postnatal stages, expressed in postnatal cortical plate and in migrating olfactory bulb interneurons in the striatal SVZ and rostral migratory stream. Expressed in the developing neuroepithelium in the region of the developing oculomotor nucleus at 11.5 dpc and 13.5 dpc (PubMed:31211835).|||Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity. Interacts with ARRB1 and ARRB2.|||Lethal at perinatal stages, with most of the neonates dying within 24 hours. Mutants display slightly enlarged heart, but no clear effect on heart functionality is observed. Mutant mice display abnormalities in semilunar valves and ventricles, myocardial degeneration and fibrosis, as well as abnormal intracortical migration of interneurons and premature invasion of the cortical plate. According to PubMed:17804806, mutants display ventricular septal and atrial septal defects. According to PubMed:21246655, mutants display ventricular septal defects but no atrial septal defects. According to PubMed:18442043, no abnormalities in semilunar valve formation or ventricular septal defects are observed. No effect on hematopoiesis, neural development and gastrointestinal vascularization is observed. No apparent bone phenotype is observed. Mutant embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (PubMed:31211835).|||Not detected in blood, liver, lung and heart, but high expression detected in several tumor cell lines (at protein level). Expressed in heart, spleen, kidney, lung, ovary, brain, testis, astrocytes, neutrophils and B-lymphocytes.|||Recycling endosome|||The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively.|||The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.|||Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner. http://togogenome.org/gene/10090:Sec11c ^@ http://purl.uniprot.org/uniprot/Q9D8V7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S26B family.|||Catalytic component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. Specifically cleaves N-terminal signal peptides that contain a hydrophobic alpha-helix (h-region) shorter than 18-20 amino acids.|||Component of the signal peptidase complex paralog C (SPC-C) composed of a catalytic subunit SEC11C and three accessory subunits SPCS1, SPCS2 and SPCS3. Within the complex, interacts with SPCS2 and SPCS3. The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids.|||Endoplasmic reticulum membrane|||May undergo processing at the N-terminus.|||The C-terminal short (CTS) helix is essential for catalytic activity. It may be accommodated as a transmembrane helix in the thinned membrane environment of the complex, similarly to the signal peptide in the complex substrates. http://togogenome.org/gene/10090:Or8g26 ^@ http://purl.uniprot.org/uniprot/Q9EQ92 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or1j20 ^@ http://purl.uniprot.org/uniprot/Q8VGJ9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Snx20 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0D0|||http://purl.uniprot.org/uniprot/Q9D2Y5 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Cell membrane|||Cytoplasm|||Early endosome membrane|||Interacts with SELPLG (By similarity). Interaction with SELPLG is controversial and was not detected in PubMed:25882846.|||May play a role in cellular vesicle trafficking (PubMed:25882846). Has been proposed to function as a sorting protein that targets SELPLG into endosomes, but has no effect on SELPLG internalization from the cell surface, nor on SELPLG-mediated cell-cell adhesion (PubMed:18196517).|||Membrane|||No visible phenotype. Mice appear healthy and normal. Neutrophils from mutant mice display unchanged Selplg-mediated cell-cell adhesion and Selplg expression at the cell membrane is unchanged.|||Nucleus|||The PX domain binds phosphatidylinositol 3-phosphate which is necessary for localization to the endosomes. http://togogenome.org/gene/10090:Atf3 ^@ http://purl.uniprot.org/uniprot/Q60765 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. ATF subfamily.|||Binds DNA as a homodimer or a heterodimer. Interacts with KAT5; promoting KAT5 autoacetylation and KAT5 deubiquitination by USP7.|||By stress.|||Nucleus|||This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters (PubMed:11916968). Represses transcription from promoters with ATF sites (PubMed:11916968). It may repress transcription by stabilizing the binding of inhibitory cofactors at the promoter (By similarity). http://togogenome.org/gene/10090:Cox18 ^@ http://purl.uniprot.org/uniprot/G5E8U6|||http://purl.uniprot.org/uniprot/Q8VC74 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the OXA1/ALB3/YidC family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Found in a complex with TMEM177, COA6, MT-CO2/COX2, COX20, SCO1 and SCO2. Interacts transiently with MT-CO2/COX2 during its maturation. Interacts with COX20 in a MT-CO2/COX2-dependent manner.|||Membrane|||Mitochondrial membrane insertase required for the translocation of the C-terminus of cytochrome c oxidase subunit II (MT-CO2/COX2) across the mitochondrial inner membrane. Plays a role in MT-CO2/COX2 maturation following the COX20-mediated stabilization of newly synthesized MT-CO2/COX2 protein and before the action of the metallochaperones SCO1/2. Essential for the assembly and stability of the mitochondrial respiratory chain complex IV (also known as cytochrome c oxidase).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Endog ^@ http://purl.uniprot.org/uniprot/O08600|||http://purl.uniprot.org/uniprot/Q3UN47 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA/RNA non-specific endonuclease family.|||Endonuclease that preferentially catalyzes the cleavage of double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA (PubMed:25355512, PubMed:32095813). The 5hmC-modified nucleotide does not increase the binding affinity, but instead increases the efficiency of cutting and specifies the site of cleavage for the modified DNAs (PubMed:32095813). Shows significantly higher affinity for four-stranded Holliday junction over duplex and single-stranded DNAs (PubMed:32095813). Promotes conservative recombination when the DNA is 5hmC-modified (PubMed:25355512). Promotes autophagy through the suppression of mTOR by its phosphorylation-mediated interaction with YWHAG and its endonuclease activity-mediated DNA damage response (PubMed:33473107). GSK3-beta mediated phosphorylation of ENDOG enhances its interaction with YWHAG, leading to the release of TSC2 and PIK3C3 from YWHAG resulting in mTOR pathway suppression and autophagy initiation (By similarity). Promotes cleavage of mtDNA in response to oxidative and nitrosative stress, in turn inducing compensatory mtDNA replication (By similarity).|||GSK3-beta-mediated phosphorylation at Thr-125 is necessary for its interaction with YWHAG and the induction of autophagy.|||Homodimer; disulfide-linked (PubMed:32192768, PubMed:32095813). Homodimerization is essential for its activity (PubMed:32192768). Interacts with YWHAG (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Ctnnd1 ^@ http://purl.uniprot.org/uniprot/E9Q8Z5|||http://purl.uniprot.org/uniprot/E9Q8Z6|||http://purl.uniprot.org/uniprot/E9Q8Z8|||http://purl.uniprot.org/uniprot/E9Q905|||http://purl.uniprot.org/uniprot/E9Q986|||http://purl.uniprot.org/uniprot/P30999 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ARM repeats 1 to 5 mediate interaction with cadherins.|||Belongs to a multiprotein cell-cell adhesion complex that also contains E-cadherin/CDH1, alpha-catenin/CTNNA1, beta-catenin/CTNNB1, and gamma-catenin/JUP. Binds to the C-terminal fragment of PSEN1 and mutually competes for CDH1 (By similarity). Interacts with ZBTB33 (PubMed:10207085, PubMed:12087177). Interacts with GLIS2 (PubMed:17344476). Interacts with FER (By similarity). Interacts with NANOS1 (via N-terminal region) (By similarity). Interacts (via N-terminus) with GNA12; the interaction regulates CDH1-mediated cell-cell adhesion (PubMed:15240885). Interacts with GNA13 (PubMed:15240885). Component of a cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (By similarity). Interacts with CCDC85B (By similarity). Interacts with PLPP3; negatively regulates the PLPP3-mediated stabilization of CTNNB1 (By similarity).|||Belongs to the beta-catenin family.|||Cell membrane|||Cytoplasm|||Expressed at the outer limiting membrane of the retina at 18.5 dpc.|||Expressed in basal keratinocytes (at protein level).|||Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability. Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics. Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors.|||Nucleus|||Phosphorylated by FER and other protein-tyrosine kinases. Phosphorylated at Ser-288 by PAK5. Dephosphorylated by PTPRJ (By similarity).|||adherens junction http://togogenome.org/gene/10090:Gjd2 ^@ http://purl.uniprot.org/uniprot/O54851 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family. Delta-type subfamily.|||Cell membrane|||Highly expressed in neurons.|||One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.|||gap junction http://togogenome.org/gene/10090:Dsc3 ^@ http://purl.uniprot.org/uniprot/P55850 ^@ Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium may be bound by the cadherin-like repeats.|||Cell membrane|||Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.|||First expressed at 13.0 dpc in epithelium of whisker pads and external nares, and in most mature vibrissa follicles. 12 hours later, prominently expressed in whiskers and tactile follicles above the eye. At 14.5 dpc, also expressed in developing nails and teeth and, at low levels, in ventral and lateral skin. At 15.5 dpc, highly expressed in general body epidermis and at 16.5 dpc, detected over entire embryo. In the adult, highly expressed in basal layers of stratified cells.|||Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.|||desmosome http://togogenome.org/gene/10090:Lmf2 ^@ http://purl.uniprot.org/uniprot/Q8C3X8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the lipase maturation factor family.|||Endoplasmic reticulum membrane|||Involved in the maturation of specific proteins in the endoplasmic reticulum. May be required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway (By similarity). http://togogenome.org/gene/10090:Asb1 ^@ http://purl.uniprot.org/uniprot/G3X9J5|||http://purl.uniprot.org/uniprot/Q3U5A0|||http://purl.uniprot.org/uniprot/Q9WV74 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Decreased spermatogenesis with less complete filling of seminiferous tubules but fertility does not appear to be affected.|||Highest expression in testis, spleen, bone marrow and salivary gland.|||Interacts with CUL5 and RNF7.|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Mediates Notch-induced ubiquitination and degradation of TCF3/E2A and JAK2 (By similarity). May play a role in testis development (PubMed:11509662).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Cldn10 ^@ http://purl.uniprot.org/uniprot/Q9Z0S6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Can form homodimers both in trans (interaction between CLDN10 molecules in opposing membranes) and in cis (interaction between CLDN10 molecules within one membrane).|||Cell membrane|||Conditional knockout in the thick ascending limb (TAL) of Henle's loop in kidney leads to hypocalcemia, hypermagnesemia, hyperphosphatemia and nephrocalcinosis.|||Detected in developing kidney at 14 dpc, with levels increasing towards adulthood. Expressed during tooth development: at 12 dpc, detected in the thickening tooth epithelium, at 13.5 dpc in the lingual basal epithelium of the bud epithelium, at 14.5 dpc in lingual epithelium and between 18 dpc to postnatal day 1 in odontoblasts and stratum intermedium.|||Endoplasmic reticulum|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Involved in the regulation of paracellular epithelia permeability to ions in multiple organs. It acts as a paracellular ion channel probably forming permselective pores; isoform 1 appears to create pores preferentially permeable to cations and isoform 2 for anions. In sweat glands and in the thick ascending limb (TAL) of Henle's loop in kidney, it controls paracellular sodium permeability which is essential for proper sweat production and renal function.|||Produced by alternative splicing of isoform 2.|||Produced by alternative splicing of isoform 3.|||Strong expression detected in brain cortex and kidney and weak expression in lung and cecum. In kidney, detected in thick ascending limb (TAL) of Henle's loop and proximal convoluted tubule (PCT). Isoform 1 is widely expressed, with highest expression detected in brain cortex, kidney and lung. Isoform 2, isoform 3, isoform 4 and isoform 5 are only detected in kidney and uterus. In kidney, the expression of isoform 1 is highest in medulla, with transcripts being detected in medullary thick ascending limb of Henle's loop (mTAL) and outer and inner medullary collecting ducts, whereas isoform 2 (along with isoform 4) is more highly expressed in cortex, with transcripts being detected in PCT, mTAL and cortical collecting duct. Expressed in the inner ear where it is detected in organ of Corti, marginal cells of stria vascularis, Reissner's membrane and spiral limbus (at protein level) (PubMed:14698084). Expressed in salivary glands and skin (PubMed:28771254).|||The fourth transmembrane region (161-181), which is missing in isoform 3, isoform 5 and isoform 6, is necessary for integration into tight junctions.|||tight junction http://togogenome.org/gene/10090:Cldn34b3 ^@ http://purl.uniprot.org/uniprot/Q80ZS5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Maco1 ^@ http://purl.uniprot.org/uniprot/Q7TQE6 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the macoilin family.|||In the embryo, stronger expression at 15.5 dpc than at 10.5 dpc or 19.5 dpc. Expression decreases after birth although significant expression remains associated with some neuronal structures at P10.|||Nucleus membrane|||Plays a role in the regulation of neuronal activity.|||Rough endoplasmic reticulum membrane|||Strong expression in whole nervous system up to 12.5 dpc. Highly expressed in all neuronal differentiation fields from 14.5 dpc to birth, with highest expression in the telencephalic cortical plate and mitral cells in the olfactory bulb, and lower expression in neuronal progenitor zones. Progressively decreased expression in fields of neuron precursor proliferation from 14.5 dpc and virtually undetectable there by 17.5 dpc. No significant expression detected outside the nervous system. After birth, significant expression remains in the cerebellum, olfactory bulb and hippocampus. http://togogenome.org/gene/10090:Xaf1 ^@ http://purl.uniprot.org/uniprot/Q5NBU8 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with BIRC1, BIRC2, BIRC3, BIRC4, BIRC7 and BIRC8. Part of an complex consisting of BIRC4, XAF1 and BIRC5; the complex formation requires IFN-beta stimulation. Interacts with RNF114, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling (By similarity).|||Mitochondrion|||Nucleus|||Probable cloning artifact.|||Seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family. Inhibits anti-caspase activity of BIRC4. Induces cleavage and inactivation of BIRC4 independent of caspase activation. Mediates TNF-alpha-induced apoptosis and is involved in apoptosis in trophoblast cells. May inhibit BIRC4 indirectly by activating the mitochondrial apoptosis pathway. After translocation to mitochondria, promotes translocation of BAX to mitochondria and cytochrome c release from mitochondria. Seems to promote the redistribution of BIRC4 from the cytoplasm to the nucleus, probably independent of BIRC4 inactivation which seems to occur in the cytoplasm. The BIRC4-XAF1 complex mediates down-regulation of BIRC5/survivin; the process requires the E3 ligase activity of BIRC4. Seems to be involved in cellular sensitivity to the proapoptotic actions of TRAIL. May be a tumor suppressor by mediating apoptosis resistance of cancer cells (By similarity). http://togogenome.org/gene/10090:Nckap1 ^@ http://purl.uniprot.org/uniprot/P28660 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates preferentially with the first SH3 domain of NCK (By similarity). Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Interacts with NYAP1, NYAP2 and MYO16.|||Belongs to the HEM-1/HEM-2 family.|||Cell membrane|||Cytoplasm|||High expression in cerebral cortex, not in cerebellar cortex.|||Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (PubMed:27605705).|||lamellipodium membrane http://togogenome.org/gene/10090:Dusp14 ^@ http://purl.uniprot.org/uniprot/Q9JLY7 ^@ Function|||Similarity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Involved in the inactivation of MAP kinases. Dephosphorylates ERK, JNK and p38 MAP-kinases. Plays a negative role in TCR signaling by dephosphorylating MAP3K7 adapter TAB1 leading to its inactivation. http://togogenome.org/gene/10090:Or6b13 ^@ http://purl.uniprot.org/uniprot/Q7TRU0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ctsll3 ^@ http://purl.uniprot.org/uniprot/Q3ULP7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase C1 family.|||Lysosome http://togogenome.org/gene/10090:Frat1 ^@ http://purl.uniprot.org/uniprot/B2RU64|||http://purl.uniprot.org/uniprot/P70339 ^@ Developmental Stage|||Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation contributes to progression of mouse T-cell lymphomas (PubMed:9034327).|||Belongs to the GSK-3-binding protein family.|||Binds DVL1. Binds GSK-3 and prevent GSK-3-dependent phosphorylation.|||Cytoplasm|||Expressed at low levels during embryonic development.|||Highly expressed in testis. Lower level of expression in spleen, thymus and brain.|||Phosphorylated.|||Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis. http://togogenome.org/gene/10090:Sumo1 ^@ http://purl.uniprot.org/uniprot/P63166 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin family. SUMO subfamily.|||By hypoxia.|||Cell membrane|||Cleavage of precursor form by SENP1 or SENP2 is necessary for function.|||Covalently attached to KCNB1; UBE2I increases cross-linking with KCNB1 and PIAS1 decreases cross-links with KCNB1 (By similarity). Interacts with SAE2, RANBP2, PIAS1 and PIAS2 (By similarity). Interacts with PRKN (By similarity). Covalently attached to a number of proteins such as IKFZ1, PML, RANGAP1, HIPK2, SP100, p53, p73-alpha, MDM2, JUN, DNMT3B and TDG (By similarity). Also interacts with HIF1A, HIPK2, HIPK3, CHD3, EXOSC9, RAD51 and RAD52 (By similarity). Interacts with USP25 (via ts SIM domain); the interaction weakly sumoylates USP25 (By similarity). Interacts with SIMC1, CASP8AP2, RNF111 and SOBP (via SIM domains) (By similarity). Interacts with BHLHE40/DEC1 (By similarity). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with MTA1 (By similarity). Interacts with SENP2 (By similarity). Interacts with HINT1 (PubMed:31088288).|||Cytoplasm|||Expressed at 13.5 dpc strongly in the upper lip, primary palate and medial edge epithelia of the secondary palate. At 14.5 dpc expression could be seen in the medial edge epithelial seam.|||Nucleus|||Nucleus membrane|||Nucleus speckle|||PML body|||Polymeric SUMO1 chains undergo polyubiquitination by RNF4.|||Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (By similarity).|||Ubiquitous. http://togogenome.org/gene/10090:Or52n20 ^@ http://purl.uniprot.org/uniprot/Q8VGV6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Amotl1 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VM69|||http://purl.uniprot.org/uniprot/Q9D4H4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the angiomotin family.|||Expressed in exocrine glands, including pancreas, submandibular gland, lacrimal gland, parotid gland and sublingual gland (at protein level).|||Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus.|||Polyubiquitinated by NEDD4, leading to proteasomal degradation.|||tight junction http://togogenome.org/gene/10090:Aktip ^@ http://purl.uniprot.org/uniprot/Q64362 ^@ Caution|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-conjugating enzyme family. FTS subfamily.|||Cell membrane|||Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3. Interacts directly with HOOK1, HOOK2 and HOOK3. The FHF complex associates with the homotypic vesicular sorting complex (the HOPS complex). Also interacts with AKT1. May interact with FHIP1A.|||Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Regulates apoptosis by enhancing phosphorylation and activation of AKT1. Increases release of TNFSF6 via the AKT1/GSK3B/NFATC1 signaling cascade. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell.|||Cytoplasm|||Defects in Aktip are a cause of embryonic death in homozygous animals. Death occurs at about 10 days of development. Symptoms include loss of left-right asymmetry, malformation of the developing brain and of the spinal cord, syndactyly and polydactyly. Heterozygous animals are characterized by polydactyly and thymic hyperplasia.|||Lacks the conserved Cys residue necessary for ubiquitin-conjugating enzyme E2 activity.|||Ubiquitous. Highest expression in kidney, testis and brain and lowest in spleen and liver. http://togogenome.org/gene/10090:Rfx2 ^@ http://purl.uniprot.org/uniprot/P48379 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RFX family.|||Cytoplasm|||Detected in the anterior primitive streak preceding the morphological appearance of the node at 7.0 dpc. Expressed in the node and in the midline notochordal plate cells extending anteriorly from the node at 7.5 dpc. At 8.5 dpc, expressed in the node now located in the tail region. At 9.5 dpc, detected in the floor plate and in the dorsal portion of the neural tube, with highest expression in the anterior portion of the spinal cord. Also expressed in the developing gut. At 10.5 dpc, also observed in the telencephalon region of the brain and in the anterior portion of the limb bud at 12.5 dpc (PubMed:26248850). Localizes to cells at the posterior margin of the ciliated organ of asymmetry (PubMed:22233545).|||Homodimer; probably only forms homodimers in testis (PubMed:15229132). Heterodimer; heterodimerizes with RFX1 and RFX3 (PubMed:15229132).|||Mice are perfectly viable but show complete male sterility (PubMed:26248850, PubMed:26162102, PubMed:26853561). Spermatogenesis proceeds normally through meiosis. However, haploid cells undergo a complete arrest in spermatid development before spermatid elongation (PubMed:26248850, PubMed:26162102). Arrested cells show altered Golgi apparatus organization, leading to a deficit in the generation of a spreading acrosomal cap from proacrosomal vesicles and merge to form giant multinucleated cells released to the epididymis. Spermatids also completely fail to form the flagellar axoneme (PubMed:26162102).|||Nucleus|||Transcription factor that acts as a key regulator of spermatogenesis (PubMed:26248850, PubMed:26162102, PubMed:26853561). Acts by regulating expression of genes required for the haploid phase during spermiogenesis, such as genes required for cilium assembly and function (PubMed:26162102, PubMed:26853561). Recognizes and binds the X-box, a regulatory motif with DNA sequence 5'-GTNRCC(0-3N)RGYAAC-3' present on promoters (PubMed:15229132, PubMed:26162102). Probably activates transcription of the testis-specific histone gene H1-6 (PubMed:15229132). http://togogenome.org/gene/10090:Megf8 ^@ http://purl.uniprot.org/uniprot/P60882 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a negative regulator of hedgehog signaling (PubMed:29290584).|||Contaminating sequence. Sequence of unknown origin in the C-terminal part.|||Highest expression in brain, testis and kidney.|||Intron retention.|||Membrane http://togogenome.org/gene/10090:Bckdhb ^@ http://purl.uniprot.org/uniprot/Q6P3A8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that forms the branched-chain alpha-keto acid decarboxylase (E1) component of the BCKD complex. The branched-chain alpha-ketoacid dehydrogenase is a large complex composed of three major building blocks E1, E2 and E3. It is organized around E2, a 24-meric cubic core composed of DBT, to which are associated 6 to 12 copies of E1, and approximately 6 copies of the dehydrogenase E3, a DLD dimer.|||Mitochondrion matrix|||Together with BCKDHA forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction. http://togogenome.org/gene/10090:Crebrf ^@ http://purl.uniprot.org/uniprot/Q8CDG5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a negative regulator of the endoplasmic reticulum stress response or unfolded protein response (UPR). Represses the transcriptional activity of CREB3 during the UPR. Recruits CREB3 into nuclear foci (By similarity).|||Belongs to the bZIP family. CREBRF subfamily.|||Highly expressed in intestin, testis, heart and kidney, weakly in brain adipose, colon, liver, lung and skeletal.|||Interacts (via leucine-zipper domain) with CREB3 (via leucine-zipper domain); the interaction promotes CREB3 degradation.|||Nucleus|||Probably degraded by the proteasome. http://togogenome.org/gene/10090:Cdc42ep5 ^@ http://purl.uniprot.org/uniprot/Q9Z0X0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BORG/CEP family.|||Endomembrane system|||Highly expressed in the skeletal muscle.|||Interacts with CDC42 in a GTP-dependent manner, and with SEPT7.|||Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts. Inhibits MAPK8 independently of CDC42 binding. Controls septin organization and this effect is negatively regulated by CDC42.|||The CRIB domain mediates interaction with CDC42.|||cytoskeleton http://togogenome.org/gene/10090:ND2 ^@ http://purl.uniprot.org/uniprot/P03893|||http://purl.uniprot.org/uniprot/Q9MD59 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I subunit 2 family.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Interacts with TMEM242 (By similarity).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Lce3d ^@ http://purl.uniprot.org/uniprot/E9Q8V1 ^@ Similarity ^@ Belongs to the LCE family. http://togogenome.org/gene/10090:Ctdsp1 ^@ http://purl.uniprot.org/uniprot/P58466 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Mg(2+) ion per monomer.|||Expression is restricted to non-neuronal tissues.|||Monomer. Interacts with REST.|||Nucleus|||Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation (By similarity). Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. http://togogenome.org/gene/10090:Cert1 ^@ http://purl.uniprot.org/uniprot/Q9EQG9 ^@ Domain|||Function|||Miscellaneous|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||Endoplasmic reticulum|||Golgi apparatus|||Interacts with VAPA and VAPB. Interaction with VAPB is less efficient than with VAPA. Interacts (via FFAT motif) with MOSPD2 (via MSP domain).|||May be due to intron retention.|||Phosphorylation on Ser-132 decreases the affinity toward phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity. Inactivated by hyperphosphorylation of serine residues by CSNK1G2/CK1 that triggers dissociation from the Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide and sphingomyelin synthesis.|||Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.|||The FFAT motif is required for interaction with VAPA, VAPB and MOSPD2.|||The PH domain targets the Golgi apparatus.|||The START domain recognizes ceramides and diacylglycerol lipids, interacts with membranes, and mediates the intermembrane transfer of ceramides and diacylglycerol lipids. http://togogenome.org/gene/10090:Actl10 ^@ http://purl.uniprot.org/uniprot/A2AKE7 ^@ Similarity ^@ Belongs to the actin family. http://togogenome.org/gene/10090:L3mbtl3 ^@ http://purl.uniprot.org/uniprot/Q8BLB7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Death at a late embryonic stage due defective erythropoiesis, defects in the maturation of other types of myeloid lineage cells and anemia.|||Detected in hematopoietic progenitor cells in fetal liver. Detected in adult bone marrow, heart, brain, spleen, lung, liver, kidney and testis.|||Interacts with RNF2. Interacts (via SAM domain) with SAMD1 (via SAM domain); the interaction mediates L3MBTL3 binding to chromatin (PubMed:33980486). Interacts with RBPJ; the interaction is required for L3MBTL3 localization to chromatin and is impaired the Notch-derived peptides containing the intracellular domain (NICD) (PubMed:29030483). Interacts (via SAM domain) with KDM1A (By similarity). Interacts with DCAF5 (PubMed:30442713). Interacts with DNMT1 (By similarity). Interacts with E2F1 (By similarity). Interacts with SOX2 (PubMed:30442713). Interacts with SFMBT1 (PubMed:30442713).|||Is a negative regulator of Notch target genes expression, required for RBPJ-mediated transcriptional repression. It recruits KDM1A to Notch-responsive elements and promotes KDM1A-mediated H3K4me demethylation (By similarity). Involved in the regulation of ubiquitin-dependent degradation of a set of methylated non-histone proteins, including SOX2. It acts as an adapter recruiting the CRL4-DCAF5 E3 ubiquitin ligase complex to methylated target proteins (PubMed:30442713). Also involved in the regulation of ubiquitin-dependent degradation of methylated DNMT1 and E2F1 (By similarity). Required for normal maturation of myeloid progenitor cells.|||Nucleus http://togogenome.org/gene/10090:Or5e1 ^@ http://purl.uniprot.org/uniprot/Q8VFZ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stoml1 ^@ http://purl.uniprot.org/uniprot/A0A0B4J1F1|||http://purl.uniprot.org/uniprot/Q8CI66 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the band 7/mec-2 family.|||Cell membrane|||Cytoplasmic vesicle|||Expressed in dorsal root ganglion neurons.|||Interacts with STOM; may redistribute STOM from the plasma membrane to late endosomes.|||Late endosome membrane|||May play a role in cholesterol transfer to late endosomes (By similarity). May play a role in modulating membrane acid-sensing ion channels. Can specifically inhibit proton-gated current of ASIC1 isoform 1. Can increase inactivation speed of ASIC3. May be involved in regulation of proton sensing in dorsal root ganglions (PubMed:24247984).|||Membrane|||Membrane raft http://togogenome.org/gene/10090:Itgae ^@ http://purl.uniprot.org/uniprot/Q60677|||http://purl.uniprot.org/uniprot/Q8BS01 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chains linked by a disulfide bond. Alpha-E associates with beta-7.|||Integrin alpha-E/beta-7 is a receptor for E-cadherin. It mediates adhesion of intra-epithelial T-lymphocytes to epithelial cell monolayers. Mice expressing a null mutation of the alpha-E subunit gene exhibit a marked reduction in the numbers of intraepithelial lymphocytes in the gut and in the development of gut-associated lymphoid aggregates, supporting a specific role for this integrin in mediating retention of lymphocytes in the intestinal wall.|||Membrane|||The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage. http://togogenome.org/gene/10090:Urah ^@ http://purl.uniprot.org/uniprot/A0A0A0MQC3|||http://purl.uniprot.org/uniprot/Q9CRB3 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the transthyretin family. 5-hydroxyisourate hydrolase subfamily.|||Catalyzes the hydrolysis of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU).|||HIU hydrolysis also occurs spontaneously, but more slowly.|||Homotetramer.|||Peroxisome http://togogenome.org/gene/10090:Mtif3 ^@ http://purl.uniprot.org/uniprot/A4QMQ0|||http://purl.uniprot.org/uniprot/Q9CZD5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IF-3 family.|||IF-3 binds to the 28S ribosomal subunit and shifts the equilibrum between 55S ribosomes and their 39S and 28S subunits in favor of the free subunits, thus enhancing the availability of 28S subunits on which protein synthesis initiation begins.|||Mitochondrion http://togogenome.org/gene/10090:Sema3d ^@ http://purl.uniprot.org/uniprot/Q8BH34 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the semaphorin family.|||Induces the collapse and paralysis of neuronal growth cones. Could potentially act as repulsive cues toward specific neuronal populations. Binds to neuropilin (By similarity).|||Secreted|||Strong binding to neuropilin is mediated by the carboxy third of the protein. http://togogenome.org/gene/10090:Chrnd ^@ http://purl.uniprot.org/uniprot/P02716|||http://purl.uniprot.org/uniprot/Q80VZ5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Delta/CHRND sub-subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (By similarity).|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Tbc1d25 ^@ http://purl.uniprot.org/uniprot/A1A5B6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a GTPase-activating protein specific for RAB33B. Involved in the regulation of autophagosome maturation, the process in which autophagosomes fuse with endosomes and lysosomes.|||Cytoplasm|||Interacts (via N-terminus) with MAP1LC3B, GABARAP and GABARAPL2.|||autophagosome http://togogenome.org/gene/10090:Vkorc1l1 ^@ http://purl.uniprot.org/uniprot/A0A0M3HEP8|||http://purl.uniprot.org/uniprot/Q6TEK5 ^@ Activity Regulation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the VKOR family.|||Detected in testis and lung.|||Endoplasmic reticulum membrane|||Inhibited by warfarin (coumadin) (PubMed:23928358). Warfarin locks VKORC1 in both redox states into the closed conformation (By similarity).|||Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K, and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.|||Membrane|||Vkorc1l1 overexpression cannot rescue the lethal phenotype of Vkorc1-deficient mice, suggesting that the protein does not play a major role in vitamin K-dependent blood coagulation. http://togogenome.org/gene/10090:Lhx5 ^@ http://purl.uniprot.org/uniprot/P61375|||http://purl.uniprot.org/uniprot/Q543P4 ^@ Function|||Subcellular Location Annotation ^@ Nucleus|||Plays an essential role in the regulation of neuronal differentiation and migration during development of the central nervous system. http://togogenome.org/gene/10090:Rhox13 ^@ http://purl.uniprot.org/uniprot/F6YCR7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the paired-like homeobox family.|||In adult testis, expressed in differentiating spermatagonia and preleptotene spermatocytes, but not during other stages of spermatogenesis (at protein level). Detected in testis from 13.5 days post coitum (dpc) onwards. Detected in ovary from 13.5 dpc, but levels gradually decline and are undetectable by 3 days post partum (dpp).|||Nucleus|||Probable transcription factor. http://togogenome.org/gene/10090:Ddhd2 ^@ http://purl.uniprot.org/uniprot/Q80Y98 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PA-PLA1 family.|||Endoplasmic reticulum-Golgi intermediate compartment|||Forms homooligomers and, to a much smaller extent, heterooligomers with DDHD1.|||It is uncertain whether Met-1 or Met-31 is the initiator.|||Phospholipase that hydrolyzes preferentially phosphatidic acid, including 1,2-dioleoyl-sn-phosphatidic acid, and phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P), phosphatidylinositol 5-phosphate (PI(5)P) and possibly phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in the maintenance of the endoplasmic reticulum and/or Golgi structures. May regulate the transport between Golgi apparatus and plasma membrane (By similarity).|||SAM and DDHD domains together are required for phospholipid binding.|||cis-Golgi network|||cytosol http://togogenome.org/gene/10090:Kcnv1 ^@ http://purl.uniprot.org/uniprot/Q8BZN2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the potassium channel family. V (TC 1.A.1.2) subfamily. Kv8.1/KCNV1 sub-subfamily.|||Cell membrane|||Heteromultimer with KCNB1 and KCNB2. Interacts with KCNC4 and KCND1 (By similarity).|||Potassium channel subunit that does not form functional channels by itself. Modulates KCNB1 and KCNB2 channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. Can down-regulate the channel activity of KCNB1, KCNB2, KCNC4 and KCND1, possibly by trapping them in intracellular membranes (By similarity).|||The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. http://togogenome.org/gene/10090:Slc36a4 ^@ http://purl.uniprot.org/uniprot/Q8CH36 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the amino acid/polyamine transporter 2 family.|||Highly expressed in hippocampus, hypothalamus and piriform cortex (at protein level) (PubMed:24530433). Expressed in epithelial cells and both inhibitory and excitatory neurons (PubMed:24530433).|||Interacts with CRYBA1.|||Lysosome membrane|||Uniporter that mediates the transport of neutral amino acids like L-tryptophan, proline and alanine. The transport activity is sodium ions-independent, electroneutral and therefore functions via facilitated diffusion. http://togogenome.org/gene/10090:Cdkn1a ^@ http://purl.uniprot.org/uniprot/P39689|||http://purl.uniprot.org/uniprot/Q564P6 ^@ Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation leads to protein stability. Acetylated in vitro on Lys-136, Lys-149, Lys-156 and Lys-158. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1.|||Belongs to the CDI family.|||By p53, mezerein (antileukemic compound) and interferon beta.|||Cytoplasm|||Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 (PubMed:20154723). Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Interacts with PIM1 (By similarity). Interacts with STK11 (PubMed:25329316). Interacts with NUAK1 (By similarity). Interacts with DTL and TRIM39 (By similarity).|||May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex (PubMed:25329316). Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (By similarity). Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (By similarity).|||Nucleus|||Phosphorylation of Thr-140 or Ser-141 impairs binding to PCNA. Phosphorylation at Ser-112 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex (By similarity). Phosphorylation of Thr-140 by PIM2 enhances its stability and inhibits cell proliferation. Phosphorylation of Thr-140 by PIM1 results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. UV radiation-induced phosphorylation at Ser-78 and Ser-141 by NUAK1 leads to its degradation.|||Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:37178686). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (PubMed:37178686). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex (PubMed:25329316). Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (By similarity).|||The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex.|||The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.|||Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Ubiquitination at Ser-2 leads to degradation by the proteasome pathway. Ubiquitinated by RNF114; leading to proteasomal degradation (By similarity). http://togogenome.org/gene/10090:Gucy1b2 ^@ http://purl.uniprot.org/uniprot/E9Q6H0|||http://purl.uniprot.org/uniprot/Q8BXH3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Cytoplasm http://togogenome.org/gene/10090:Sphk1 ^@ http://purl.uniprot.org/uniprot/Q8CI15 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetyltransferase activity increases in presence of the kinase substrate, sphingosine (PubMed:29662056). In Purkinje cells, kinase activity on sphingosine increases in presence of VEGFA (PubMed:25417698). In neurons, kinase activity increases during the first 24h in presence of Amyloid-beta protein 42 to decrease after 96h (By similarity).|||At 10.5 dpc, expressed in the whole brain, with the highest levels in the telencephalon.|||Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions (PubMed:17346996, PubMed:21084291, PubMed:25417698, PubMed:29662056, PubMed:33334894). Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol (PubMed:9726979). In contrast to proapoptotic SPHK2, has a negative effect on intracellular ceramide levels, enhances cell growth and inhibits apoptosis (PubMed:16118219). Involved in the regulation of inflammatory response and neuroinflammation. Via the product sphingosine 1-phosphate, stimulates TRAF2 E3 ubiquitin ligase activity, and promotes activation of NF-kappa-B in response to TNF signaling (By similarity). In response to TNF and in parallel to NF-kappa-B activation, negatively regulates RANTES induction through p38 MAPK signaling pathway (By similarity). Involved in endocytic membrane trafficking induced by sphingosine, recruited to dilate endosomes, also plays a role on later stages of endosomal maturation and membrane fusion independently of its kinase activity (PubMed:27806293, PubMed:28049734). In Purkinje cells, seems to be also involved in the regulation of autophagosome-lysosome fusion upon VEGFA (PubMed:25417698).|||Cell membrane|||Cytoplasm|||Endosome membrane|||Has serine acetyltransferase activity on PTGS2/COX2 in an acetyl-CoA dependent manner. The acetyltransferase activity increases in presence of the kinase substrate, sphingosine. During neuroinflammation, through PTGS2 acetylation, promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.|||Interacts with ACY1 (PubMed:15196915). Binds to calmodulin. Interacts with SPHKAP (By similarity). Interacts with CIB1, the interaction occurs in a calcium-dependent manner (By similarity). Interacts with TRAF2 (By similarity). Interacts with EEF1A1; the interaction enhances SPHK1 kinase activity (By similarity).|||Mutants are viable, fertile and without any obvious abnormalities (PubMed:15459201). Mutant mice show reduced SPP levels in serum (PubMed:16314531, PubMed:15459201). Conditional mutants in neurons exhibit a decrease of amyloid-beta phagocytic activity (PubMed:29662056). Double knockout for SPHK1 and SPHK2 causes embryonic lethality (PubMed:16314531). Between 11.5 dpc and 12.5 dpc embryos exhibit cranial hemorrhage and die at 13.5 dpc (PubMed:16314531). At 11.5 dpc the wall of the dorsal aorta is poorly developed and endothelial cells are severely defective in all blood vessels in the mesenchymal region of the head (PubMed:16314531). Double knockout embryos also show a neural tube deffect (PubMed:16314531).|||Nucleus|||Synapse|||Widely expressed (PubMed:9726979). Expressed in brain (at protein level). Detected in neurons. http://togogenome.org/gene/10090:Dync1li2 ^@ http://purl.uniprot.org/uniprot/Q6PDL0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.|||Belongs to the dynein light intermediate chain family.|||Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1H1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H.|||cytoskeleton http://togogenome.org/gene/10090:Slc12a3 ^@ http://purl.uniprot.org/uniprot/P59158|||http://purl.uniprot.org/uniprot/Q543E4 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC12A transporter family.|||Cell membrane|||Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:15068971, PubMed:17488636, PubMed:19633012, PubMed:36370249). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (PubMed:26099046). May act either independently of IL18R1, or in a complex with IL18R1 (PubMed:26099046).|||Expressed predominantly in kidney, including in distal tubules (at protein level). Detected at low levels in heart, lung and liver. Not detected in normal aorta, but abundantly expressed in fatty streaks and advanced atherosclerotic lesions. In atherosclerotic lesions, expressed in macrophages, smooth muscle cells and endothelial cells (at protein level).|||Homodimer. Interacts with KLHL3 (By similarity). Interacts with IL18R1; this interaction is increased by IL18 treatment (PubMed:26099046).|||In macrophages and T-lymphocytes, up-regulated by IL18. In endothelial cells and smooth muscle cells, up-regulated by IL1B, IL18 and TNF (at protein level).|||Interaction between the cytoplasmic N-terminal and C-terminal domains (NTD and CTD, respectively) is essential for SLC12A3/NCC transporter activity. Phosphorylation by OXSR1/OSR1 and STK39/SPAK may activate SLC12A3/NCC by facilitating this interaction.|||Membrane|||Phosphorylated at Thr-53, Thr-58 and Ser-71 by OXSR1/OSR1 and STK39/SPAK downstream of WNK4, promoting its activity (PubMed:16263722, PubMed:17488636, PubMed:19633012). Phosphorylated in response to IL18 (PubMed:26099046).|||Phosphorylation by OXSR1/OSR1 and STK39/SPAK in kidney distal convoluted tubules promotes its activity (PubMed:16263722, PubMed:17488636, PubMed:19633012). Also activated by OXSR1/OSR1 and STK39/SPAK downstream of WNK3 (By similarity). Inhibited by thiazide-type diuretic metolazone (PubMed:15068971). Thiazide drugs, such as polythiazide, specifically inhibit SLC12A3/NCC transporter activity by competing with chloride for binding (By similarity).|||Simultaneous knockout of APOE and SLC12A3 results lower plasma Mg(2+) compared to plasma levels in wild-type and APOE knockout animals. Simultaneous knockdown of APOE and SLC12A3 shows no significant differences in aortic root atherosclerotic lesion intima area and thoracic-abdominal aorta lipid deposition as compared to APOE and double APOE and IL18R1 knockout animals. In contrast, simultaneous knockdown of APOE, SLC12A3 and IL18R1 results in significantly smaller aortic root intimal size and decreased thoracic-abdominal aorta lipid deposition. The triple knockout mice exhibit lower plasma K(+) and Mg(2+) compared to plasma levels in wild-type animals. The effect on atherosclerosis is due to IL18 activation of bone marrow-derived leukocytes, and possibly vascular cells, rather than to kidney tubular disorders or electrolyte disturbances.|||Ubiquitinated; ubiquitination is essential for regulation of endocytosis. http://togogenome.org/gene/10090:Fbxo38 ^@ http://purl.uniprot.org/uniprot/Q8BMI0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Conditional deletion in T-cells does not affect the development, peripheral homeostasis and population of memory T-cells, but leads to faster tumor progression (PubMed:30487606). Faster tumor progression is caused by higher levels of Pdcd1/PD-1 in tumor-infiltrating T-cells (PubMed:30487606).|||Expressed at high levels in embryo (developing brain, spinal chord, branchial arms and limbs) (PubMed:14729953). Widely expressed at low levels in adult tissues, with highest expression in testis. Expressed in postmeiotic spermatids (PubMed:14729953).|||In embryo expressed at 11 dpc, 15 dpc and 17 dpc.|||Nucleus|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO38) composed of CUL1, SKP1, RBX1 and FBXO38 (By similarity). Interacts with KLF7 (PubMed:14729953). Interacts with PDCD1/PD-1 (By similarity).|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of PDCD1/PD-1, thereby regulating T-cells-mediated immunity (PubMed:30487606). Required for anti-tumor activity of T-cells by promoting the degradation of PDCD1/PD-1; the PDCD1-mediated inhibitory pathway being exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (PubMed:30487606). May indirectly stimulate the activity of transcription factor KLF7, a regulator of neuronal differentiation, without promoting KLF7 ubiquitination (PubMed:14729953, PubMed:16990251).|||Up-regulated by IL2 (PubMed:30487606). Down-regulated in tumor-infiltrating T-cells (PubMed:30487606).|||cytosol http://togogenome.org/gene/10090:Gk2 ^@ http://purl.uniprot.org/uniprot/Q9WU65 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FGGY kinase family.|||Cytoplasm|||Interacts with PLD6 (PubMed:28852571). Interacts with ARMC12 (PubMed:33536340).|||Key enzyme in the regulation of glycerol uptake and metabolism. Essential for male fertility and sperm mitochondrial sheath formation (PubMed:28852571, PubMed:30662012). Required for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during spermatogenesis.(PubMed:30662012). Can induce mitochondrial clustering through interactions with PLD6 and up-regulation of phosphatidic acid synthesis in the mitochondria (PubMed:28852571).|||Male mice are infertile due to dysfunctional spermatozoa, which exhibit unregulated ATP production, disordered mitochondrial sheath formation, abnormal mitochondrial morphology, and defective sperm tail (PubMed:30662012, PubMed:33536340). Spermatozoa cannot transit the uterotubal junction due to reduced motility leading to male infertility (PubMed:33536340). Spermatids exhibit abnormal arrangement of crescent-like mitochondria, which causes a disorganization of the mitochondrial sheath (PubMed:33536340).|||Mitochondrion outer membrane|||Testis-specific. http://togogenome.org/gene/10090:Nkx6-3 ^@ http://purl.uniprot.org/uniprot/B2RU70|||http://purl.uniprot.org/uniprot/Q3UHX8 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in the developing CNS and gastro-intestinal tract.|||In the developing embryo, it is confined to the gut and caudal hindbrain. In caudal hindbrain, it is specifically expressed in a subpopulation of differentiating V2 neurons. Not detected prior to 12.5 dpc and is not found in motor nuclei. At 12.5 dpc, it is expressed in the ventral medial aspect of the medullary reticular formation (MDR). At 16.5 dpc, expression is confined to the gigantocellular nucleus, a nucleus that is part of the MDR. In addition to the CNS, it is also expressed in the developing gut, in duodenal and glandular stomach endoderm and, at the end of gestation becomes restricted to the base of the gastric units in the glandular stomach. Expressed at very low level in the pancreatic epithelium. Expressed in the pancreas at 15.5 dpc.|||Nucleus|||Putative transcription factor, which may be involved in patterning of central nervous system and pancreas. http://togogenome.org/gene/10090:Map3k21 ^@ http://purl.uniprot.org/uniprot/Q8VDG6 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subunit ^@ Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Homodimer. Interacts with TLR4.|||Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation.|||Negative regulator of TLR4 signaling. Does not activate JNK1/MAPK8 pathway, p38/MAPK14, nor ERK2/MAPK1 pathways (By similarity). http://togogenome.org/gene/10090:Guca1a ^@ http://purl.uniprot.org/uniprot/P43081 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds three calcium ions (via EF-hands 2, 3 and 4) when calcium levels are high. Binds Mg(2+) when calcium levels are low.|||Guca1a and Guca1b double knockout mice show an increase in response to light in dark-adapted cone photoreceptors (PubMed:25673692). Dark-adapted cone photoreceptors show a delayed response time and a delayed recovery time in response to light (PubMed:25673692). Guca1a, Guca1b and Rcvrn triple knockout mice show rod photoreceptors have a reduced current decay during light response (PubMed:29435986).|||Homodimer.|||In the retina, expressed in rod photoreceptors (at protein level) (PubMed:9620085). Expressed in cone photoreceptors (PubMed:9620085).|||Membrane|||Photoreceptor inner segment|||Stimulates retinal guanylyl cyclase when free calcium ions concentration is low and inhibits guanylyl cyclase when free calcium ions concentration is elevated (By similarity). This Ca(2+)-sensitive regulation of retinal guanylyl cyclase is a key event in recovery of the dark state of rod photoreceptors following light exposure (By similarity). May be involved in cone photoreceptor light response and recovery of response in bright light (PubMed:25673692).|||photoreceptor outer segment http://togogenome.org/gene/10090:Scgb1b24 ^@ http://purl.uniprot.org/uniprot/B1B0N6 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Sergef ^@ http://purl.uniprot.org/uniprot/Q80YD6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with SEC5. The interaction occurs only in the presence of magnesium or manganese and is stimulated by dCTP or GTP (By similarity).|||Nucleus|||Probable guanine nucleotide exchange factor (GEF), which may be involved in the secretion process. http://togogenome.org/gene/10090:Tm4sf1 ^@ http://purl.uniprot.org/uniprot/Q64302 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the L6 tetraspanin family.|||Highly expressed in skin and lung. Moderately expressed in lymph nodes and kidneys. Also present in thymic stroma and fibroblasts.|||Membrane|||Present in high molecular weight complexes in tumor cells. Interacts with SDCBP2 (By similarity). http://togogenome.org/gene/10090:Havcr2 ^@ http://purl.uniprot.org/uniprot/Q8VIM0 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the T-cell and airway phenotype regulator (Tapr) locus, a single chromosomal region that confers reduced T-helper type 2 responsiveness and protects against airway hyperactivity (AHR), the hallmark of human asthma.|||Belongs to the immunoglobulin superfamily. TIM family.|||Cell junction|||Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:18006747). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556006, PubMed:18006747). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits (By similarity). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (PubMed:21807895). Expressed on Treg cells can inhibit Th17 cell responses (By similarity). Receptor for LGALS9. Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6 (PubMed:22863785). Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (PubMed:20937702). However, the function as receptor for LGALS9 has been challenged (By similarity). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (PubMed:24567532). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent (PubMed:20083673). May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells (PubMed:19224762). Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells (PubMed:20083673). Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha (PubMed:18006747). In tumor-imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid-sensing and trafficking of nucleid acids to endosomes (PubMed:22842346). Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13 (PubMed:17620455). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity (By similarity). Negatively regulates NK cell function in LPS-induced endotoxic shock (PubMed:25337993).|||Endogenous expression on dendritic cells is proposed to act as a negative regulator of chemotherapy-induced antitumor responses.|||Experimental results based on the injection of HAVCR2/TIM-3 antibodies or use of HAVCR2/TIM-3-Fc fusion proteins can reflect changes in the activity of several cell types and pathways as HAVCR2/TIM-3 is expressed by multiple immune cell types.|||Expressed in T-helper type 1 lymphocytes. Not expressed by naive T-cells but up-regulated as they differentiate into T-helper-1 cells. Also expressed by differentiated type 1 CD8+ cytotoxic T-cells. Expressed on peritoneal exudate macrophages, monocytes, and splenic dendritic cells (DCs). Expression on natural killer (NK) cells is inversely associated with IFN-gamma production during the initial 24 hours of LPS-induced endotoxic shock. Expressed on mast cells.|||In vivo administration of antibody to HAVCR2 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease and increases the number and activation level of macrophages.|||Interacts with HMGB1; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (PubMed:22842346). Interacts with BAG6 (PubMed:22863785). Interacts (phosphorylated) with PIK3R1 and PIK3R2. Interacts (not dependent on its phosphorylation status) with FYN (PubMed:21807895). Interacts (in basal state T-cells) with VAV1; AKT1/2, LCP2, ZAP70, SYK, PIK3R1, FYN, SH3BP2 and SH2D2A. Interacts (in activated T-cells) with LCK and PLCG (By similarity). Interacts with ILF3; this interaction promotes ILF3 ubiquitination and degradation (By similarity).|||Membrane|||N-glycosylated.|||Phosphorylated on tyrosine residues; modestly increased after TCR/CD28 stimulation. Can be phosphorylated in the cytoplasmatic domain by FYN (PubMed:21807895). Phosphorylation at Tyr-256 is increased by stimulation with ligand LGALS9 (By similarity).|||Polymorphic differences between BALB/c and HBA alleles in the Ig-like V-type domain are the reason for distinct binding affinities for PtSer. The HBA2 allele binds PtSer approximately 50% less than BALB/c.|||Secreted|||The Ig-like V-type (immunoglobulin-like) domain mediates binding to PtSer involving a Ca(2+) ion. http://togogenome.org/gene/10090:Paics ^@ http://purl.uniprot.org/uniprot/Q9DCL9 ^@ Function|||Similarity|||Subunit ^@ Bifunctional phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase catalyzing two reactions of the de novo purine biosynthetic pathway.|||Homooctamer.|||In the C-terminal section; belongs to the AIR carboxylase family. Class II subfamily.|||In the N-terminal section; belongs to the SAICAR synthetase family. http://togogenome.org/gene/10090:Zkscan5 ^@ http://purl.uniprot.org/uniprot/Q69ZT2|||http://purl.uniprot.org/uniprot/Q6PAK4|||http://purl.uniprot.org/uniprot/Q9Z1D8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus|||Testis specific. http://togogenome.org/gene/10090:Or1j21 ^@ http://purl.uniprot.org/uniprot/Q8VGK5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Odorant receptor. Activated by (+) and (-)-carvone. http://togogenome.org/gene/10090:Anapc2 ^@ http://purl.uniprot.org/uniprot/Q8BZQ7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the cullin family.|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (By similarity). In the context of the APC/C complex, directly interacts with UBE2C and UBE2S (By similarity). Interacts (via cullin domain) with ANAPC11 and with UBCH10 (By similarity). Interacts with NEUROD2 (PubMed:19900895). Interacts with FBXO43; the interaction is direct.|||Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation. http://togogenome.org/gene/10090:Ube2v1 ^@ http://purl.uniprot.org/uniprot/Q9CZY3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation (By similarity). Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity). Together with RNF135 and UBE2N, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (By similarity). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway.|||Heterodimer with UBE2N. Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity. Interacts with TRAF6 (By similarity).|||Nucleus|||Ubiquitous. Highly expressed in heart, brain, liver, skeletal msucle, kidney and testis. Detected at lower levels in lung and spleen. http://togogenome.org/gene/10090:Sgpl1 ^@ http://purl.uniprot.org/uniprot/Q8R0X7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the group II decarboxylase family. Sphingosine-1-phosphate lyase subfamily.|||Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine (PubMed:9464245, PubMed:20097939). Elevates stress-induced ceramide production and apoptosis (PubMed:9464245). Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts (PubMed:20097939, PubMed:28262793). Involved in the regulation of pro-inflammatory response and neutrophil trafficking (PubMed:21173151). Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP (PubMed:28521611). Seems to play a role in establishing neuronal contact sites and axonal maintenance (By similarity).|||Endoplasmic reticulum membrane|||Expressed throughout mouse embryogenesis.A transient increase is observed from 5.5 dpc to 7.5 dpc.|||Highest levels are found in liver, small intestine and thymus, followed by kidney, lung, heart, spleen and brain (at protein level). Also detected in stomach, testis and skeletal muscle (at protein level).|||Mutant animals have a shortened lifespan (PubMed:21173151). Mutant mice show an increase of sphingoid base phosphates, but also other sphingolipids (including sphingosine, ceramide, and sphingomyelin) in the serum and/or liver, resulting in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol (PubMed:20097939). They are deficient in B and T lymphocytes yet have high blood levels of neutrophils and monocytes along with elevated expression of pro-inflammatory cytokines. Their tissues are largely clear of infiltrating leukocytes and their neutrophils are defective in migration to chemotactic stimulus (PubMed:21173151). Mice lacking Sgpl1 exhibit complete podocyte foot process effacement and absence of slit diaphragms in kidney (PubMed:9464245, PubMed:28165339). They display hypoalbuminemia and an elevated urinary albumin/creatinine ratio (PubMed:28165339). They also display abnormal adrenal gland morphology and defective expression of enzymes involved in steroidogenesis in this tissue (PubMed:28165343). Conditional knockout in brain significantly reduces phosphoethanolamine levels with alterations in basal and stimulated autophagy involving decreased conversion of LC3-I to LC3-II, increased levels of lysosomal markers and aggregate-prone proteins such as APP and SNCA. Animals show profound deficits in cognitive skills (PubMed:28521611). http://togogenome.org/gene/10090:Pcyt1a ^@ http://purl.uniprot.org/uniprot/P49586 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cytidylyltransferase family.|||Brain and liver (at protein level) (PubMed:12842190). Also found in heart, kidney, spleen, lung, skeletal muscle, ovary and testis (PubMed:12842190).|||By phosphorylation.|||Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.|||Endoplasmic reticulum|||Homodimer.|||Membrane|||Monoubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.|||Nucleus|||The serine residues of the C-terminus are phosphorylated. The inactive soluble form is stabilized by phosphorylation, the active membrane bound form is promoted by anionic lipids or diacylglycerol, and is stabilized by dephosphorylation (By similarity).|||cytosol http://togogenome.org/gene/10090:Asxl2 ^@ http://purl.uniprot.org/uniprot/B2RUG8|||http://purl.uniprot.org/uniprot/D6REV1|||http://purl.uniprot.org/uniprot/Q8BJR0|||http://purl.uniprot.org/uniprot/Q8BZ32 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Asx family.|||Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which may be required for an association with nuclear receptors.|||Interacts with PPARA and PPARG.|||Nucleus|||Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility. Involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as peroxisome proliferator-activated receptor gamma (PPARG). Acts as coactivator for PPARG and enhances its adipocyte differentiation-inducing activity; the function seems to involve differential recruitment of acetylated and methylated histone H3 (By similarity). http://togogenome.org/gene/10090:Meioc ^@ http://purl.uniprot.org/uniprot/A2AG06 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed specifically in fetal ovary and postnatal and adult testes (at protein level) (PubMed:26742488). In adult testis expressed in spermatocytes, beginning in preleptotene and extending through most stages of meiotic prophase I, including leptotene, zygotene, and pachytene (PubMed:28380054).|||In the ovary appears at 13.5 dpc and disappears shortly after. In postnatal testes, expression increases between 5 and 10 dpp and is maintained through adulthood. In male and female germal cells present from preleptotene to diplotene stages of meiosis prophase I.|||Interacts with YTHDC2; binds transcripts that regulate the mitotic cell cycle inhibiting progression into metaphase, thereby allowing meiotic prophase to proceed normally (PubMed:26742488, PubMed:28380054, PubMed:29033321). Interacts with RBM46 (PubMed:36001654).|||Is required for meiosis completion in both male and female germ cells. Confers stability to numerous meiotic mRNAs in gonads allowing proper initiation and progression into meiosis prophase I. The function may involve YTHDC2 and is independent of induction by retinoic acid (RA). Maintains an extended meiotic prophase I by properly promoting the transition from a mitotic to a meiotic cell cycle program by binding transcripts through its interaction with YTHDC2 that regulate the mitotic cell cycle (PubMed:28380054).|||Normal growth but mice are fully infertile with barely detectable ovaries and testes at adulthood. Complete absence of follicles in the ovaries and spermatozoon in the seminiferous tubules and epidymides. In testis, approximately 60% of the tubules contain spermatocytes arrested early in meiosis prophase I, the rest contains only spermatogonia. Testes completely lack postmeiotic germ cells, and are depleted for meiotic germ cells. In some individuals, germ cells does not progress past preleptotene, while in others, germ cells advanced to the zygotene stage of meiotic prophase (PubMed:28380054).|||Nucleus http://togogenome.org/gene/10090:Gm13287 ^@ http://purl.uniprot.org/uniprot/B1AYI3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Tcf25 ^@ http://purl.uniprot.org/uniprot/B2ZAC8|||http://purl.uniprot.org/uniprot/Q8R3L2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCF25 family.|||Broadly expressed in the embryo during the early stages of organogenesis with highest levels in dorsal root ganglia and little or no expression in liver and skin.|||Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (By similarity). In the RQC complex, required to promote formation of 'Lys-48'-linked polyubiquitin chains during ubiquitination of incompletely synthesized proteins by LTN1 (By similarity). Also acts as a transcriptional repressor: represses transcription of SRF in vitro and so may play a role in heart development (By similarity). May play a role in cell death control (PubMed:18068114).|||Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase LTN1, TCF25 and NEMF associated with the 60S ribosomal subunit (By similarity). Interacts with XIAP (PubMed:18068114).|||Nucleus|||The C-terminal region mediates transcriptional repression.|||cytosol http://togogenome.org/gene/10090:Or5bh3 ^@ http://purl.uniprot.org/uniprot/Q8VF35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nek6 ^@ http://purl.uniprot.org/uniprot/Q9ES70 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. Phosphorylation at Ser-206 is required for its activation. Phosphorylated upon IR or UV-induced DNA damage. Phosphorylated by CHEK1 and CHEK2. Interaction with APBB1 down-regulates phosphorylation at Thr-210 (By similarity).|||Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108.|||Cytoplasm|||Displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9 (By similarity).|||Highly expressed in the liver.|||Interacts with NEK9, predominantly in mitosis. Interacts with KIF11 (via C-terminus). Interacts with APBB1 (via WW domain). Interacts with ANKRA2, ATF4, ARHGAP33, CDC42, CIR1, PRAM1, PTN, PRDX3, PIN1, RAD26L, RBBP6, RPS7, RPS6KB1 and TRIP4 (By similarity). Interacts with STAT3.|||Nucleus|||Nucleus speckle|||Protein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis. Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, TRIP4, RPS6KB1 and histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle formation. Involved in G2/M phase cell cycle arrest induced by DNA damage. Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (By similarity). Phosphorylates STAT3 (PubMed:20595392). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (By similarity).|||centrosome|||spindle pole http://togogenome.org/gene/10090:C1ql2 ^@ http://purl.uniprot.org/uniprot/Q8CFR0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Forms homotrimers which can further assemble to form higher-order oligomeric complexes. Interacts with ADGRB3. May interact with ERFE. Forms heterooligomers with C1QL3 and C1QL4, when proteins are coexpressed; this interaction does not occur after secretion.|||Glycosylated, but not with N-linked glycans.|||Highest expression in eye, followed by placenta and brain, intermediate expression in adipose tissue and lowest expression in lymph node and testis.|||May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses.|||Secreted http://togogenome.org/gene/10090:Nlrp1a ^@ http://purl.uniprot.org/uniprot/Q2LKU9 ^@ Activity Regulation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as the sensor component of the Nlrp1a inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (PubMed:23219391). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (By similarity). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, and mediates the formation of the inflammasome polymeric complex (By similarity). In response to pathogen-associated signals, the N-terminal part of Nlrp1a is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the inflammasome recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (By similarity). In the absence of GSDMD expression, the Nlrp1a inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME) (By similarity). Activation of Nlrp1a inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (By similarity). When activated in the bone marrow, induces the pyroptosis of hematopoietic stem cells and progenitor cells of both myeloid and lymphoid lineages, hence allowing the removal of damaged cells, and the release of IL1B, which induces granulopoiesis (PubMed:23219391).|||Autocatalytically cleaved. Autocatalytic cleavage in FIIND region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal parts remain associated non-covalently.|||Belongs to the NLRP family.|||Constitutes the active part of the Nlrp1a inflammasome (By similarity). In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, N-terminus), preventing activation of the Nlrp1a inflammasome (By similarity). In response to pathogen-associated signals, the N-terminal part of Nlrp1a is degraded by the proteasome, releasing this form, which polymerizes to form the Nlrp1a inflammasome complex: the Nlrp1a inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis (By similarity).|||Constitutes the precursor of the Nlrp1a inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals.|||Cytoplasm|||Highly expressed in hematopoietic stem cells and progenitor cells of both myeloid and lymphoid origin (PubMed:23219391). The expression is highly strain-dependent. Not expressed in Balb/cJ animals, but widely expressed in C57BL/6J. Expressed in macrophages resistant to Bacillus anthracis lethal toxin, but not in toxin-sensitive macrophages, except in CAST/EiJ strain (PubMed:23506131).|||Inflammasome|||Interacts (via LRR repeats) with BCL2 and BCL2L1 (via the loop between motifs BH4 and BH3) (By similarity). Interacts with NOD2; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and increases IL1B release (By similarity). Interacts with EIF2AK2/PKR; this interaction requires EIF2AK2 activity, is accompanied by EIF2AK2 autophosphorylation and promotes inflammasome assembly in response to danger-associated signals (By similarity). Interacts with MEFV; this interaction targets Nlrp1a to degradation by autophagy, hence preventing excessive IL1B- and IL18-mediated inflammation (By similarity). Interacts with DPP9; leading to inhibit activation of the inflammasome (By similarity). DPP9 acts via formation of a ternary complex, composed of a DPP9 homodimer, one full-length Nlrp1a protein, and one cleaved C-terminus of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) (By similarity). Interacts with DPP8; leading to inhibit activation of the inflammasome, probably via formation of a ternary complex with DPP8 (By similarity).|||Interacts with the C-terminal part of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in absence of pathogens and other damage-associated signals.|||Interacts with the N-terminal part of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, N-terminus) in absence of pathogens and other damage-associated signals (By similarity). Homomultimer; forms the Nlrp1a inflammasome polymeric complex, a filament composed of homopolymers of this form in response to pathogens and other damage-associated signals (By similarity). Interacts (via CARD domain) with CASP1 (via CARD domain); leading to CASP1 activation (By similarity).|||Nlrp1a inflammasome is activated by pathogens and other damage-associated signals: activation promotes ubiquitination and degradation of the N-terminal part, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome (By similarity). Nlrp1a inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus) in a ternary complex, thereby preventing Nlrp1a oligomerization and activation (By similarity). Nlrp1a inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9 (PubMed:31383852). Val-boroPro relieves inhibition of DPP8 and/or DPP9 by promoting disruption of the ternary complex, releasing its C-terminal part from autoinhibition (By similarity).|||Nucleus|||Regulatory part that prevents formation of the Nlrp1a inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of Nlrp1a (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), preventing activation of the Nlrp1a inflammasome (By similarity). In response to pathogen-associated signals, this part is ubiquitinated and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the Nlrp1a inflammasome (By similarity).|||The C-terminal part of Nlrp1a oligomerizes to form the core of the Nlrp1a inflammasome filament: in the filament, the CARD domains form a central helical filaments that are promoted by oligomerized, but flexibly linked, UPA regions surrounding the filaments. The UPA region reduces the threshold needed for filament formation and signaling.|||The FIIND (domain with function to find) region is involved in homomerization, but not in CASP1-binding. Autocatalytic cleavage in this region occurs constitutively, prior to activation signals, and is required for inflammasome activity (IL1B release), possibly by facilitating CASP1 binding. Both N- and C-terminal fragments remain associated.|||The leucine-rich repeat (LRR) domain may be involved in autoinhibition in the absence of activating signal, possibly through intramolecular interaction with the NACHT domain.|||Three tandem Nrlp1 paralogs, Nrlp1a, Nrlp1b and Nrlp1c, are present in at least 2 strains, C57BL/6J and 129S1/SvImJ. Nlrp1c is predicted to be a pseudogene. Nlrp1b is the primary mediator of macrophage susceptibility to Bacillus anthracis lethal toxin (LT). Neither Nlrp1a, nor Nrlp1c are expressed in anthrax lethal toxin susceptible strains, hence neither of them is thought to play an important role in this phenotype.|||Ubiquitinated in response to pathogen-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1a, C-terminus), which polymerizes and forms the Nlrp1a inflammasome.|||cytosol http://togogenome.org/gene/10090:Vmn1r135 ^@ http://purl.uniprot.org/uniprot/K9J7G0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Creg1 ^@ http://purl.uniprot.org/uniprot/O88668 ^@ Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CREG family.|||Found at low level from 7 dpc and increased during embryonic development.|||Homodimer. Interacts with IGF2R; the interaction is dependent on glycosylation (By similarity).|||Induced during differentiation.|||May contribute to the transcriptional control of cell growth and differentiation. Antagonizes transcriptional activation and cellular transformation by the adenovirus E1A protein. The transcriptional control activity of cell growth requires interaction with IGF2R (By similarity).|||N-glycosylated.|||Secreted|||Widely expressed. http://togogenome.org/gene/10090:Plcb2 ^@ http://purl.uniprot.org/uniprot/A3KGF7|||http://purl.uniprot.org/uniprot/E9PYI3 ^@ Cofactor|||Function|||Miscellaneous|||Subunit ^@ Binds 1 Ca(2+) ion per subunit.|||Interacts with RAC1. Forms a complex composed of at least WDR26, a G-beta:gamma unit, and PLCB2.|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.|||The receptor-mediated activation of PLC-beta-2 is most effectively mediated by one G-protein alpha subunit, alpha-16. http://togogenome.org/gene/10090:Homer3 ^@ http://purl.uniprot.org/uniprot/Q99JP6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Homer family.|||Cytoplasm|||Expressed in the cerebellum, hippocampus, lung and thymus.|||Knockout mice show severe autoimmune phenotypes, with lymphocyte infiltration of multiple organs and hyperplasia in lymph nodes by 10 weeks of age.|||Postsynaptic density|||Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses (By similarity). Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA (PubMed:18218901).|||Synapse|||Tetramer (By similarity). Isoform 1 and isoform 2 encode coiled-coil structures that mediate homo- and heteromultimerization. Interacts with NFATC2; interaction is calcium independent; interaction competes with PPP3CA for NFATC2 binding; interaction is reduced by AKT activation (PubMed:18218901). Interacts with NFATC1 and NFATC4. Interacts with SHANK1; forms a high-order complex at least composed of SHANK1 and HOMER3; the complex formation is regulated by CAMK2A-mediated phosphorylation (By similarity).|||The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3. http://togogenome.org/gene/10090:Lect2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0R8|||http://purl.uniprot.org/uniprot/O88803 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the LECT2/MIM-1 family.|||Has a neutrophil chemotactic activity. Also a positive regulator of chondrocyte proliferation.|||Highly expressed in liver and weakly in testis. Not expressed in heart, brain, spleen, lung, skeletal muscle and kidney.|||Secreted http://togogenome.org/gene/10090:Pdik1l ^@ http://purl.uniprot.org/uniprot/Q8QZR7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Nucleus http://togogenome.org/gene/10090:Nol12 ^@ http://purl.uniprot.org/uniprot/Q8BG17 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RRP17 family.|||Continuously expressed during embryogenesis.|||Expressed in brain, lung, spleen, kidney and heart.|||Interacts with KIAA1191.|||May bind to 28S rRNA. In vitro binds single-stranded nucleic acids.|||nucleolus http://togogenome.org/gene/10090:Nlrp10 ^@ http://purl.uniprot.org/uniprot/Q8CCN1 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NLRP family.|||Cell membrane|||Cytoplasm|||Despite its official name, does not contain LRR repeats.|||Expressed in skin, tongue, heart, colon and several cell lines of hematopoietic and myocytic origin but not in kidney, skeletal muscle, spleen, liver, lung, thymus, brain or small intestine (at protein level).|||High susceptibility to systemic infection by C.albicans with 100% mortality by day 16 post-infection (PubMed:23071280). Does not alter Nlrp3 inflammasome activity and up-regulates Gdpd3 expression (PubMed:22538615). Does not impair skin repair after wounding (PubMed:27221772). Also does not impair the irritant contact dermatitis response following treatment with the irritant croton oil (PubMed:27221772). Significantly reduced inflammation in dinitrofluorobenzene-induced contact hypersensitivity response with reduced numbers of CD3(+), CD8(+) and CD4(+) T cells (PubMed:27221772).|||Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID (By similarity). Displays anti-inflammatory activity (By similarity). Required for immunity against C.albicans infection (PubMed:23071280). Involved in the innate immune response by contributing to pro-inflammatory cytokine release in response to invasive bacterial infection (By similarity). Contributes to T-cell-mediated inflammatory responses in the skin (PubMed:27221772). Plays a role in protection against periodontitis through its involvement in induction of IL1A via ERK activation in oral epithelial cells infected with periodontal pathogens (By similarity). Exhibits both ATPase and GTPase activities (By similarity).|||Oligomerizes (By similarity). Interacts with PYCARD (By similarity). Also interacts with CASP1 and IL1B (PubMed:15096476). Interacts with NOD1 and components of the NOD1 signaling pathway including RIPK2, NR2C2/TAK1 and IKBKG/NEMO (By similarity).|||The NACHT domain is required for inhibition of CASP1 autoprocessing.|||The pyrin and ATP-binding domains are required to elicit cytokine release following bacterial infection.|||Was originally thought to play a role in adaptive immunity through control of dendritic cell-mediated antigen transport to lymph nodes from peripheral sites (PubMed:22538615). However, this was later shown to be dependent on DOCK8 (PubMed:26605525). http://togogenome.org/gene/10090:Nup54 ^@ http://purl.uniprot.org/uniprot/Q8BTS4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NUP54 family.|||Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane.|||Component of the p62 complex, a complex composed of NUP62, NUP54, and the isoform p58 and isoform p45 of NUP58. Interacts with NUTF2.|||Contains FG repeats.|||Nucleus membrane|||O-glycosylated.|||nuclear pore complex http://togogenome.org/gene/10090:4930402F06Rik ^@ http://purl.uniprot.org/uniprot/A2AUQ8|||http://purl.uniprot.org/uniprot/Q14BP7 ^@ Cofactor|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Membrane http://togogenome.org/gene/10090:Tmem121 ^@ http://purl.uniprot.org/uniprot/Q80XA0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM121 family.|||Displays strong neural pattern at 8.5 dpc to 12.5 dpc. Not expressed in the heart.|||May play a role in MAPK signaling.|||Membrane http://togogenome.org/gene/10090:Sema3g ^@ http://purl.uniprot.org/uniprot/Q4LFA9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Has chemorepulsive activities for sympathetic axons. Ligand of NRP2.|||Highly expressed in lung and kidney. Weakly expressed in brain.|||Secreted http://togogenome.org/gene/10090:Smndc1 ^@ http://purl.uniprot.org/uniprot/Q8BGT7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with spliceosomes. Associates with U4/U5/U6 tri-snRNP and with U2 snRNP (By similarity).|||Belongs to the SMN family.|||Cajal body|||Involved in spliceosome assembly (By similarity).|||Nucleus speckle|||The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins. http://togogenome.org/gene/10090:Atosb ^@ http://purl.uniprot.org/uniprot/Q8BR27 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ATOS family.|||Nucleus|||The protein contains a transactivation domain (TAD) which may be required for transcriptional activation of a subset of target genes.|||Transcription regulator that syncronizes transcriptional and translational programs to promote macrophage invasion of tissues. http://togogenome.org/gene/10090:Tusc2 ^@ http://purl.uniprot.org/uniprot/Q9WVF8 ^@ PTM|||Similarity ^@ Belongs to the TUSC2 family.|||Myristoylation is required for tumor suppressor activity. http://togogenome.org/gene/10090:Zfp706 ^@ http://purl.uniprot.org/uniprot/B2RVQ7|||http://purl.uniprot.org/uniprot/Q9D115 ^@ Developmental Stage|||Function|||Subcellular Location Annotation ^@ Cytoplasm|||Nucleus|||Present in self-renewing embryonic stem cells (ESCs). Does not increase significantly at the onset of differentiation.|||Transcription repressor involved in the exit of embryonic stem cells (ESCs) from self-renewal. Acts by repressing expression of KLF4. http://togogenome.org/gene/10090:Lig3 ^@ http://purl.uniprot.org/uniprot/Q3UC82|||http://purl.uniprot.org/uniprot/Q80ZH7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ATP-dependent DNA ligase family.|||Nucleus http://togogenome.org/gene/10090:Mcur1 ^@ http://purl.uniprot.org/uniprot/Q9CXD6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC90 family.|||Conditional knockout mice lacking Mcur1 in cardiomyocytes and endothelial cells are viable and are born at the expected Mendelian. They however show impaired mitochondrial calcium uptake and mitochondrial calcium uniporter (MCU) current.|||Interacts (via coiled coil regions) with MCU; the interaction is direct. Interacts with SMDT1/EMRE; the interaction is direct. Interacts with PPIF.|||Key regulator of mitochondrial calcium uniporter (MCU) required for calcium entry into mitochondrion. Plays a direct role in uniporter-mediated calcium uptake via a direct interaction with MCU. Probably involved in the assembly of the membrane components of the uniporter complex (uniplex).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nppb ^@ http://purl.uniprot.org/uniprot/P40753|||http://purl.uniprot.org/uniprot/Q54AE9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the natriuretic peptide family.|||Cardiac hormone that plays a key role in mediating cardio-renal homeostasis (PubMed:8182124). May also function as a paracrine antifibrotic factor in the heart (PubMed:10737768). Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins that drive various biological responses (PubMed:8182124). Likely involved in regulating the extracellular fluid volume and maintaining the fluid-electrolyte balance through natriuresis, diuresis, kaluresis and chloruresis (By similarity).|||Expressed abundantly in the ventricle, and in a lesser extent in the atrium (at protein level).|||Mice are viable and fertile and do not display gross skeletal abnormalities. Fluid-electrolyte balance and blood pressure remain normal although an increased rate of focal fibrotic lesions is observed within the cardiac ventricles.|||Secreted|||The precursor molecule is proteolytically cleaved by the endoprotease Furin to produce brain natriuretic peptide 45 (By similarity). May undergo further proteolytic cleavage by various proteases such as DPP4, MME and possibly FAP, to give rise to a variety of shorter peptides (By similarity). May be cleaved at Ser-91 by the prolyl endopeptidase FAP (seprase) activity (in vitro) (By similarity). May be degraded by IDE (By similarity). During IDE degradation, the resulting products initially increase the activation of NPR1 and can also stimulate NPR2 to produce cGMP before the fragments are completely degraded and inactivated by IDE (in vitro) (By similarity). http://togogenome.org/gene/10090:Pla2g4e ^@ http://purl.uniprot.org/uniprot/Q50L42 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium-dependent N-acyltransferase involved in the biosynthesis of N-acyl ethanolamines (NAEs) in the brain (PubMed:27399000). Transfers the sn-1 fatty acyl chain of phosphatidylcholine (fatty acyl donor) to the amine group of phosphatidylethanolamine (fatty acyl acceptor) to generate N-acyl phosphatidylethanolamine (NAPE). Similarly can use plasmenylethanolamine as a fatty acyl acceptor to form N-acyl plasmenylethanolamine (N-Acyl-PlsEt). Both NAPE and N-Acyl-PlsEt can serve as precursors of bioactive NAEs like N-arachidonoyl phosphatidylethanolamine also called anandamide (PubMed:27399000, PubMed:29447909). Has weak phospholipase A2 and lysophospholipase activities (PubMed:27399000, PubMed:15866882). Regulates intracellular membrane trafficking that requires modulation of membrane curvature as it occurs by enrichment in lysophospholipids. Promotes tubule formation involved in clathrin-independent endocytotic trafficking and cargo recycling (PubMed:24413173).|||Cell membrane|||Early endosome membrane|||Lysosome membrane|||Predominantly expressed in brain, heart, skeletal muscle, testis and thyroid (PubMed:15866882, PubMed:27399000). Expressed in neurons but not astrocytes or microglia (PubMed:27399000). Expressed at lower level in stomach (PubMed:15866882).|||Stimulated by cytosolic Ca(2+) (PubMed:27399000, PubMed:29447909). Stimulated by anionic phospholipids such as phosphatidylserine (PubMed:29447909).|||The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity).|||cytosol http://togogenome.org/gene/10090:Acvr2b ^@ http://purl.uniprot.org/uniprot/P27040 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Forms an activin receptor complex with activin type II receptors such as ACVR1B. Interacts with VPS39. Interacts with DYNLT1. Interacts with BMP3 (PubMed:22074949). Interacts with BMP2 (By similarity). Interacts with BMP6 (By similarity).|||Phosphorylated. Constitutive phosphorylation is in part catalyzed by its own kinase activity (By similarity).|||Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor (By similarity). http://togogenome.org/gene/10090:Esam ^@ http://purl.uniprot.org/uniprot/Q925F2 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can mediate aggregation most likely through a homophilic molecular interaction.|||Cell membrane|||Expression in 8.5 dpc-9.5 dpc embryos is observed in embryonic blood vessels including the dorsal aorta, intersomitic arteries and the forming vascular plexus in the head as well as the cardiac outflow tract. By 10.5 dpc-11.5 dpc embryos expression is found in association with the all recognizable blood vessels and in association with cells lining the heart chambers. At 10.5-days embryos expression is associated with syncytiotrophoblasts and cytotrophoblasts as well as endothelial cells associated with blood vessels in the decidua. Expression decreased after mid-gestation from 15.5-day embryos.|||Highly expressed in the heart and lung. Weakly expressed in the kidney and skin. Expression is restricted to the vascular endothelial cells. Expressed in the kidney, heart and tongue (at protein level). Also expressed on megakaryocytes and activated platelets.|||Interacts with MAGI1.|||Up-regulated on the surface of platelets upon activation.|||adherens junction|||tight junction http://togogenome.org/gene/10090:2510002D24Rik ^@ http://purl.uniprot.org/uniprot/Q3U595 ^@ Similarity ^@ Belongs to the UPF0545 family. http://togogenome.org/gene/10090:Emc6 ^@ http://purl.uniprot.org/uniprot/Q9CQW0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMC6 family.|||Component of the ER membrane protein complex (EMC).|||Endoplasmic reticulum membrane|||Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. http://togogenome.org/gene/10090:Myo1f ^@ http://purl.uniprot.org/uniprot/Q8CG29 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Tnfrsf22 ^@ http://purl.uniprot.org/uniprot/Q9ER62 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Receptor for the cytotoxic ligand TNFSF10/TRAIL. Lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis. Protects cells against TRAIL mediated apoptosis possibly through ligand competition. Cannot induce the NF-kappa-B pathway.|||Secreted|||Ubiquitous. http://togogenome.org/gene/10090:Or4a66 ^@ http://purl.uniprot.org/uniprot/Q7TR14 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dipk1a ^@ http://purl.uniprot.org/uniprot/Q9D6I7 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Among the many cysteines in the lumenal domain, most are probably involved in disulfide bonds.|||Belongs to the DIPK family.|||Endoplasmic reticulum membrane|||Ubiquitous. http://togogenome.org/gene/10090:Vmn2r100 ^@ http://purl.uniprot.org/uniprot/E9QAZ9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Nceh1 ^@ http://purl.uniprot.org/uniprot/Q8BLF1 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 'GDXG' lipolytic enzyme family.|||Cell membrane|||Hydrolyzes 2-acetyl monoalkylglycerol ether (1-O-alkyl-2-acetyl-sn-glycerol), the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (PubMed:18164358, PubMed:20625037). May be responsible for the hydrolysis of cholesterol esters (such as cholesteryl (9Z-octadecenoate)) in macrophages (PubMed:18782767). Also involved in organ detoxification by hydrolyzing exogenous organophosphorus compounds (PubMed:15840715, PubMed:16978018, PubMed:18164358).|||Inhibited by bulky trifluoromethyl ketones.|||Mice are phenotypically normal but more sensitive to organophosphorus insecticide toxicity.|||Microsome|||N-glycosylated.|||Present in brain, heart, kidney, lung, spinal cord and testis but not liver (at protein level). Expressed in peritoneal macrophages and kidney. http://togogenome.org/gene/10090:Mindy4 ^@ http://purl.uniprot.org/uniprot/A0A0N4SVL4|||http://purl.uniprot.org/uniprot/Q3UQI9 ^@ Function|||Similarity ^@ Belongs to the MINDY deubiquitinase family. FAM188 subfamily.|||Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.|||Probable hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins. http://togogenome.org/gene/10090:Thumpd1 ^@ http://purl.uniprot.org/uniprot/Q99J36 ^@ Function|||Similarity|||Subunit ^@ Belongs to the THUMPD1 family.|||Functions as a tRNA-binding adapter to mediate NAT10-dependent tRNA acetylation modifying cytidine to N4-acetylcytidine (ac4C).|||Interacts with NAT10. Binds tRNA. http://togogenome.org/gene/10090:Cd164 ^@ http://purl.uniprot.org/uniprot/Q9R0L9 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD164 family.|||Cell membrane|||During embryogenesis, expression in found in all stages examined, with the highest levels of expression at early stages (8.5 dpc) and moderate levels of expression being found at mid- to late stages of embryogenesis. Expressed during early stages of skeletal muscle development. At embryonic stages 9.5 dpc and 10.5 dpc, expressed strongly in the dorsal somite (the structure of origin for skeletal muscle precursors). It is also expressed at later stages of muscle development;.|||Endosome membrane|||Expressed at high levels in the submaxillary gland and kidney, at moderate levels in the brain, heart, lung, liver, intestine, testis, muscle and bone marrow, and at low levels in the pancreas, spleen and thymus. In the ear, expressed in the inner and outer hair cells of the organ of Corti, cells of Kolliker's organ, cells in the lateral cochlear wall behind the spiral prominence and cells of the stria vascularis (PubMed:26197441).|||Highly N- and O-glycosylated; contains sialic acid.|||Interacts with CXCR4.|||Lysosome membrane|||Sialomucin that may play a key role in hematopoiesis. May be involved in cell adhesion (By similarity). Promotes myogenesis by enhancing CXCR4-dependent cell motility. Positively regulates myoblast migration and promotes myoblast fusion into myotubes. http://togogenome.org/gene/10090:Dusp6 ^@ http://purl.uniprot.org/uniprot/Q9DBB1 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cytoplasm|||Inactivates MAP kinases. Has a specificity for the ERK family (By similarity). Plays an important role in alleviating acute postoperative pain (PubMed:24155322, PubMed:28405172). Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (PubMed:24155322). Also important for dephosphorylation of MAPK1/3 in local wound tissue, which further contributes to resolution of acute pain (PubMed:28405172).|||Interacts with MAPK1/ERK2.|||Mice exhibit a persistent state of mechanical allodynia following plantar incision (PubMed:24155322, PubMed:28405172). This allodynia phenotype is concurrent with long-lasting spinal phosphorylation of MAPK1/3 and MAP kinase p38 (PubMed:24155322). Tissue at the local incision site also shows prolonged expression of phosphorylated MAPK1/3 which persists through to post-operative day 12, although levels of phosphorylated MAP kinase p38 are normal (PubMed:28405172).|||Up-regulated in local wound tissue 5-7 days after surgical incision. http://togogenome.org/gene/10090:C8a ^@ http://purl.uniprot.org/uniprot/A2A997|||http://purl.uniprot.org/uniprot/A2A998|||http://purl.uniprot.org/uniprot/Q8K182 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complement C6/C7/C8/C9 family.|||Cell membrane|||Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C8A inserts into the target membrane, but does not form pores by itself (By similarity).|||Heterotrimer of 3 chains: alpha, beta and gamma. The alpha and gamma chains are disulfide bonded. Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b sequentially binds C6, C7, C8 and multiple copies of the pore-forming subunit C9 (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Paqr8 ^@ http://purl.uniprot.org/uniprot/Q80ZE5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ADIPOR family.|||Cell membrane|||Expressed in brain and testis.|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(i) mediated pathway (By similarity). May be involved in oocyte maturation (PubMed:12601167). Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone (By similarity). http://togogenome.org/gene/10090:Irag2 ^@ http://purl.uniprot.org/uniprot/Q60664 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IRAG2 family.|||Chromosome|||Cytoplasm|||Endoplasmic reticulum membrane|||Interacts (via coiled-coil domain) with ITPR3 (PubMed:20071408). Interacts with SUN1 and SUN2 (PubMed:29878215). Interacts with microtubules (PubMed:29878215).|||Nucleus envelope|||Plays a role in the delivery of peptides to major histocompatibility complex (MHC) class I molecules; this occurs in a transporter associated with antigen processing (TAP)-independent manner. May play a role in taste signal transduction via ITPR3. May play a role during fertilization in pronucleus congression and fusion (PubMed:9314557). Plays a role in maintaining nuclear shape, maybe as a component of the LINC complex and through interaction with microtubules (PubMed:29878215).|||Spleen and thymus. Expressed at high levels in pre B-cells, mature B-cells and pre T-cells. Expressed at low levels in mature T-cells and plasma B-cells. Expressed in circumvallate (CV), foliate (FL) and fungiform (FF) taste papillae cells of the tongue epithelium.|||The removal of the C-terminal lumenal domain occurs by proteolytic processing.|||centrosome|||spindle pole http://togogenome.org/gene/10090:Or10a3m ^@ http://purl.uniprot.org/uniprot/Q8VFZ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccdc50 ^@ http://purl.uniprot.org/uniprot/Q810U5 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc, strong punctate expression in the otic mesenchyme. Detected in the cells lining the lumen of the primitive cochlear duct and in the nerve fibers of the spiral ganglion, as well as in the nerve fibers invading the cochlear epithelium. At 17.5 dpc, detected only in the mesenchyme around the cochlear duct. 2 days after birth (P2), the mesenchymal expression becomes weaker, except in the region of the spiral limbus, while expression is observed for the first time in the apical region of the developing pillar cells (PCs). Also observed in the cytoplasm of outer hair cells, in their innervating nerve fibers and in the marginal cells of stria vascularis. At P9 and P12, detected in the stria vascularis and strongly through the entire length of the inner and outer PCs. At these stages, in tissues of mesenchymal origin, restricted to the spiral limbus and the spiral ligament. At P14 and P16, strong expression is maintained in the PCs and in the marginal cells of the stria vascularis, weak expression in the spiral limbus and ligament. Also detected in Deiter's cells. At P19 and P22, intense expression in the PCs and stria vascularis, as well as in the cell bodies and processes of Deiter's cells. Weak expression in the spiral limbus and ligament. At P31, when the inner ear is functionally mature, expressed only in the PCs and stria vascularis. At P69, strong expression in the PCs and less intense in stria vascularis. In the vestibular maculae and the cristae ampullaris, expression similar to that observed in the cochlea: strong signal in the mesenchyme at the initial embryonic stages that progressively becomes weaker and is less prominent in the adult (P33). At 17.5 dpc and P2, observed in nerve fibers innervating the sensory epithelia. Expression in the vestibular epithelium starts at 17.5 dpc and is readily detected at P2. Later expression increases and persists in adult stages in which it is restricted to the apical cytoplasm of the epithelial cells (at protein level).|||Cytoplasm|||Interacts with RNF126.|||Involved in EGFR signaling.|||Phosphorylated on tyrosine residues.|||Widely expressed. http://togogenome.org/gene/10090:Foxi1 ^@ http://purl.uniprot.org/uniprot/Q922I5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in intercalated cells of the epithelium of the distal renal tubule.|||Expressed in the entire otic vesicle at stage 9.5 dpc gradually restricted to the epithelium of the endolymphatic ducts at stage 16.5 dpc.|||Mice are deaf, impaired in their sense of balance and suffer from distal renal tubular acidosis.|||Nucleus|||Transcriptional activator required for the development of normal hearing, sense of balance and kidney function. Required for the expression of SLC26A4/PDS, JAG1 and COCH in a subset of epithelial cells and the development of the endolymphatic system in the inner ear. Also required for the expression of SLC4A1/AE1, SLC4A9/AE4, ATP6V1B1 and the differentiation of intercalated cells in the epithelium of distal renal tubules. http://togogenome.org/gene/10090:Mier1 ^@ http://purl.uniprot.org/uniprot/Q5UAK0 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with HDAC1. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2.|||Nucleus|||Transcriptional repressor regulating the expression of a number of genes including SP1 target genes. Probably functions through recruitment of HDAC1 a histone deacetylase involved in chromatin silencing.|||Ubiquitously expressed. Isoform 1 is only expressed in testis. http://togogenome.org/gene/10090:Ppil1 ^@ http://purl.uniprot.org/uniprot/B9EJX8|||http://purl.uniprot.org/uniprot/Q9D0W5 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclophilin-type PPIase family.|||Belongs to the cyclophilin-type PPIase family. PPIL1 subfamily.|||Identified in the spliceosome C complex. Interacts with SNW1/SKIP. Interacts with CDC40/PRP17; this interaction leads to CDC40 isomerization. Interacts with RBM22.|||Inhibited by Cyclosporin A.|||Involved in pre-mRNA splicing as component of the spliceosome (PubMed:33220177). PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). Catalyzes prolyl peptide bond isomerization in CDC40/PRP17 (By similarity). Plays an important role in embryonic brain development; this function is independent of its isomerase activity (PubMed:33220177).|||Mutant mice, in which PPIL1 is truncated at position 102, die before 12.5 dpc.|||Nucleus|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.|||Widely expressed in the developing cortex at 14.5 dpc. http://togogenome.org/gene/10090:Adam4 ^@ http://purl.uniprot.org/uniprot/Q8CGQ2 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Rnf114 ^@ http://purl.uniprot.org/uniprot/Q9ET26 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated. Polyubiquitinated in the presence of E2 enzymes UBE2D1, UBE2D2 and UBE2D3, but only monoubiquitinated in the presence of UBE2E1.|||Cytoplasm|||E3 ubiquitin-protein ligase that promotes the ubiquitination of various substrates. In turn, participates in the regulation of many biological processes including cell cycle, apoptosis, osteoclastogenesis as well as innate or adaptive immunity. Acts as negative regulator of NF-kappa-B-dependent transcription by promoting the ubiquitination and stabilization of the NF-kappa-B inhibitor TNFAIP3. May promote the ubiquitination of TRAF6 as well. Acts also as a negative regulator of T-cell activation. Inhibits cellular dsRNA responses and interferon production by targeting MAVS component for proteasomal degradation. Ubiquitinates the CDK inhibitor CDKN1A leading to its degradationand probably also CDKN1B and CDKN1C. This activity stimulates cell cycle G1-to-S phase transition and suppresses cellular senescence. May play a role in spermatogenesis.|||Interacts with XAF1, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling.|||Mice show no significant difference of viral resistance or augmented antiviral responses compared to WT when both are infected with virus.|||Nucleus http://togogenome.org/gene/10090:Gpr52 ^@ http://purl.uniprot.org/uniprot/P0C5J4 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in brain, especially in striatum (PubMed:24587241). Expressed in the striatum, nucleus accumbens, and lateral globus pallidus (PubMed:28583861).|||G- protein coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (By similarity). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241, PubMed:28583861). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).|||GPR52 is located within an intron of RABGAP1L gene, which exhibits epistatic effects on GPR52-mediated modulation of HTT levels by blocking this modulation.|||Gpr52 knockout mice are normal in body and brain weight. In the open field test, mice stay and move around the central zone significantly longer. The total distance traveled and brain morphology are normal. Mice are much more sensitive to the startle response following dizocilpine administration. Thus mice displayed psychosis-related behaviors (PubMed:24587241). Mice exhibit a significantly higher istradefylline-induced locomotor activity (PubMed:28583861). http://togogenome.org/gene/10090:Gm13279 ^@ http://purl.uniprot.org/uniprot/Q8CD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Tbc1d31 ^@ http://purl.uniprot.org/uniprot/Q6NXY1 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Interacts with PJA2; the interaction is direct and recruits PJA2 to centrosomes. Interacts with OFD1; regulates its activity in cilium assembly. Interacts with PRKACA.|||Intron retention.|||Molecular adapter which is involved in cilium biogenesis. Part of a functional complex including OFD1 a centriolar protein involved in cilium assembly. Could regulate the cAMP-dependent phosphorylation of OFD1, and its subsequent ubiquitination by PJA2 which ultimately leads to its proteasomal degradation.|||Probable cloning artifact.|||centriolar satellite|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Zfp414 ^@ http://purl.uniprot.org/uniprot/Q9DCK4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Usp22 ^@ http://purl.uniprot.org/uniprot/Q5DU02 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C19 family. UBP8 subfamily.|||Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H, TAF10, TRRAP and USP22. Within the SAGA complex, ATXN7L3, ENY2 and USP22 form a subcomplex required for histone deubiquitination. Interacts directly with ATXN7L3; leading to its recruitment to the SAGA complex. Interacts with ATXN7L3 and weakly with ATXN7L3B.|||Highly expressed between 10.5 dpc and 12.5 dpc. Expressed in the midbrain, forebrain, hindbrain and dorsal root ganglia of embryos at 12.5 dpc.|||Highly expressed in brain and weakly in other organs.|||Histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complex SAGA. Catalyzes the deubiquitination of both histones H2A and H2B, thereby acting as a coactivator. Recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation and cell cycle progression (By similarity).|||Nucleus http://togogenome.org/gene/10090:Csnk1d ^@ http://purl.uniprot.org/uniprot/Q3UBT6|||http://purl.uniprot.org/uniprot/Q3USK2|||http://purl.uniprot.org/uniprot/Q9DC28 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. May be dephosphorylated by PP1.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.|||Cell membrane|||Cytoplasm|||Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (PubMed:29191835). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.|||Exhibits substrate-dependent heparin activation. Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation (By similarity).|||Expressed ubiquitously. However, kinase activity is not uniform, with highest kinase activity in splenocytes.|||Golgi apparatus|||Lethal. There are fewer embryos than expected at late stages of gestation; they weigh about 30% less than control animals, but appear otherwise normal. Mice die shortly after birth. Tissue-specific disruption increases the half-life of PER2 protein and alters circadian protein expression dynamics.|||Monomer (By similarity). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (PubMed:11779462). Interacts directly with PER1 and PER2 which may lead to their degradation (By similarity). Interacts with MAP1A (By similarity). Interacts with MAPT/TAU, DBNDD2, AIB1/NCOA3 and ESR1 (By similarity). Interacts with AKAP9/AKAP450; this interaction promotes centrosomal subcellular location (By similarity). Binds to tubulins in mitotic cells upon DNA damage (By similarity). Interacts with GJA1 (By similarity). Interacts with SNAPIN (PubMed:17101137). Interacts with DNMT1 (PubMed:20192920). Interacts with DDX3X; this interaction enhances CSNK1D kinase activity in vitro, but it is unclear whether this interaction is physiologically relevant (By similarity).|||Nucleus|||centrosome|||perinuclear region|||spindle http://togogenome.org/gene/10090:Gpatch2 ^@ http://purl.uniprot.org/uniprot/Q7TQC7 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Enhances the ATPase activity of DHX15 in vitro.|||Interacts with DHX15.|||Nucleus speckle|||nucleolus http://togogenome.org/gene/10090:Pkdcc ^@ http://purl.uniprot.org/uniprot/Q5RJI4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Down-regulated by hedgehog (Hh) signaling.|||Expressed throughout embryogenesis and in adulthood. During embryogenesis, expression is high at transition phases of mesenchymal cell differentiation such as from mesenchymal cells to chondrocytes and from mesenchymal to mesothelial cells. Expressed throughout all stages of humerus bone formation. During lung development, expressed in all mesenchymal cells at the early pseudoglandular stage. Expression is rapidly lost from the mesenchyme of the lung interstitium during the mid-to-late pseudoglandular stage but continues throughout life in the mesothelial pleural cells.|||Golgi apparatus|||Morphological defects at birth including growth retardation, short limbs, cleft palate, sternal dysraphia, shortened intestine and cyanosis. Long bones display reduced mineralization due to delayed chondrocyte differentiation. Neonates breathe abnormally, do not suckle and die within a day after birth, probably due to insufficient respiration as a result of the cleft palate.|||N-glycosylated.|||Phosphorylated on tyrosines; probably via autophosphorylation.|||Secreted|||Secreted tyrosine-protein kinase that mediates phosphorylation of extracellular proteins and endogenous proteins in the secretory pathway, which is essential for patterning at organogenesis stages. Mediates phosphorylation of MMP1, MMP13, MMP14, MMP19 and ERP29 (PubMed:25171405). May also have serine/threonine protein kinase activity (PubMed:25171405). Required for longitudinal bone growth through regulation of chondrocyte differentiation (PubMed:19097194, PubMed:23792766). May be indirectly involved in protein transport from the Golgi apparatus to the plasma membrane (PubMed:19465597). Probably plays a role in platelets: rapidly and quantitatively secreted from platelets in response to stimulation of platelet degranulation (PubMed:25171405).|||Strongly expressed in adult heart, liver and testis with weak expression in brain, spleen, lung and thymus. In the humerus, strongly expressed in early flat proliferative chondrocytes. In the embryo, expressed in the anterior visceral endoderm and anterior primitive streak at 6.5 dpc. At 7.5 dpc, expressed in the anterior definitive endoderm (ADE) and anterior mesoderm but not in the notochord. At 8.0 dpc, expressed in the ADE and anterior embryonic mesoderm. At 8.5 dpc, expressed more broadly in anterior tissues and at the midline of the neural plate in the midbrain region as well as the lateral margins of the neural plate posterior to the metencephalic region. Also weakly expressed in the anterior mesenchyme. At 9.5 dpc, strongest expression in branchial arches and limb buds. During mid-gestation, expression continues in mesenchymal cells, particularly in areas where these cells condense. http://togogenome.org/gene/10090:Camk2n2 ^@ http://purl.uniprot.org/uniprot/B2RXL5|||http://purl.uniprot.org/uniprot/Q78WH7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CAMK2N family.|||Interacts with CAMK2A and CAMK2B in the presence of Ca(2+)/calmodulin or after autophosphorylation.|||Nucleus|||Potent and specific cellular inhibitor of CaM-kinase II (CAMK2) (By similarity). Traps Ca(2+)/calmodulin on CAMK2 (By similarity).|||Synapse|||cytosol http://togogenome.org/gene/10090:Upp2 ^@ http://purl.uniprot.org/uniprot/A2APN2|||http://purl.uniprot.org/uniprot/Q3UEN1|||http://purl.uniprot.org/uniprot/Q8BLN7|||http://purl.uniprot.org/uniprot/Q8CGR7|||http://purl.uniprot.org/uniprot/Q8R093 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ A conditional disulfide bridge can form within the protein that dislocates a critical phosphate-coordinating arginine Arg-100 away from the active site, disabling the enzyme.|||Belongs to the PNP/UDP phosphorylase family.|||Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate (PubMed:14715930). The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (Probable).|||Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.|||Directly up-regulated in liver by HNF-4-alpha (HNF4A) binding to the promoter. May also be indirectly regulated by signaling via various orphan nuclear receptors. Strongly up-regulated by a liver X receptor (LXR) agonist. Slightly up-regulated by a pregnane X receptor (PXR) agonist. Strongly repressed by a peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonist. Slightly repressed by a farnesoid X receptor (FXR) agonist. Shows a diurnal expression pattern with peak levels 12 hours after light onset and lowest levels 0 hours after light onset.|||Homodimer.|||Liver specific. http://togogenome.org/gene/10090:Ggt6 ^@ http://purl.uniprot.org/uniprot/Q6PDE7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the gamma-glutamyltransferase family.|||Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.|||Heterodimer composed of the light and heavy chains. The active site is located in the light chain.|||Hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors.|||Membrane http://togogenome.org/gene/10090:Cbr4 ^@ http://purl.uniprot.org/uniprot/Q91VT4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Component of the heterotetramer complex KAR (3-ketoacyl-[acyl carrier protein] reductase or 3-ketoacyl-[ACP] reductase) that forms part of the mitochondrial fatty acid synthase (mtFAS). Beta-subunit of the KAR heterotetramer complex, responsible for the 3-ketoacyl-ACP reductase activity of the mtFAS, reduces 3-oxoacyl-[ACP] to (3R)-hydroxyacyl-[ACP] in a NADPH-dependent manner with no chain length preference, thereby participating in mitochondrial fatty acid biosynthesis. The homotetramer has NADPH-dependent quinone reductase activity (in vitro), hence could play a role in protection against cytotoxicity of exogenous quinones. As a heterotetramer, it can also reduce 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro).|||Homotetramer (in vitro). Heterotetramer with HSD17B8; contains two molecules each of HSD17B8 and CBR4. Does not form homotetramers when HSD17B8 is coexpressed, only heterotetramers (in vitro).|||Mitochondrion matrix http://togogenome.org/gene/10090:P2ry2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J289|||http://purl.uniprot.org/uniprot/P35383 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. The affinity range is UTP = ATP > ATP-gamma-S >> 2-methylthio-ATP = ADP.|||Spleen, testis, kidney, liver, lung, heart and brain. http://togogenome.org/gene/10090:Abraxas2 ^@ http://purl.uniprot.org/uniprot/Q3TCJ1|||http://purl.uniprot.org/uniprot/Z4YJY0 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although strongly related to the ABRAXAS1 protein, lacks the C-terminal pSXXF that constitutes a specific recognition motif for the BRCT domain of BRCA1.|||Belongs to the FAM175 family. Abro1 subfamily.|||Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (By similarity). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (PubMed:21195082). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage. Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (By similarity).|||Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts with BRCC3/BRCC36; the interaction is direct. Interacts with BABAM1. Does not interact with BRCA1. Interacts with SHMT1 and SHMT2; the interaction is direct. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. The BRISC complex binds monoubiquitin and both 'Lys-48'- and 'Lys-63'-linked polyubiquitin. Identified in complexes with IFNAR1, IFNAR2 and SHMT2. Interacts with THAP5 (By similarity). Interacts with ATF4 (PubMed:22974638). Identified in a complex with p53/TP53 and USP7; interacts directly with both proteins. Interacts with NUMA1. Interacts with microtubule minus ends. Binds polyubiquitin (By similarity).|||Cytoplasm|||Detected in heart (at protein level).|||Interaction with THAP5 has been shown in human, but rodents lack a THAP5 homolog.|||Mice are viable and fertile, and are protected against toxic shock caused by bacterial lipopolysaccharide (LPS). IFNAR1 'Lys-63'-linked ubiquitination and IFNAR1 internalization are increased.|||Nucleus|||Up-regulated in heart in response to ischemia and reperfusion (at protein level).|||cytoskeleton|||spindle pole http://togogenome.org/gene/10090:Csf3r ^@ http://purl.uniprot.org/uniprot/P40223 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 2 subfamily.|||Found in bone marrow.|||Homodimer. The dimeric receptor binds two CSF3 molecules. Interacts with CEACAM1; down-regulates the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (PubMed:21029969).|||Membrane|||N-glycosylated.|||Receptor for granulocyte colony-stimulating factor (CSF3). In addition it may function in some adhesion or recognition events at the cell surface.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Cbs ^@ http://purl.uniprot.org/uniprot/Q91WT9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Allosterically activated by S-adenosyl-methionine/AdoMet. Activated by S-adenosylhomocysteine/AdoHcy. Binds non-covalently to a heme group that may control the redox sensitivity of the enzyme.|||Belongs to the cysteine synthase/cystathionine beta-synthase family.|||Cytoplasm|||Homotetramer.|||Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (By similarity). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (By similarity).|||Nucleus http://togogenome.org/gene/10090:Lpcat3 ^@ http://purl.uniprot.org/uniprot/Q91V01 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the membrane-bound acyltransferase family.|||Detected ubiquitously, with high expression levels in small intestine, brown adipose tissue, liver, kidney and testis (PubMed:18287005, PubMed:28846071, PubMed:25898003, PubMed:25806685, PubMed:24206663). Expressed in liver and both proximal and distal small intestine (at protein level) (PubMed:25898003). Expressed in peritoneal macrophages (PubMed:24206663).|||Endoplasmic reticulum membrane|||Expressed at late embryonic stages between 18.5 and 19.5 dpc in intestine and liver.|||Lysophospholipid O-acyltransferase (LPLAT) that catalyzes the reacylation step of the phospholipid remodeling process also known as the Lands cycle (PubMed:18287005, PubMed:25898003). Catalyzes transfer of the fatty acyl chain from fatty acyl-CoA to 1-acyl lysophospholipid to form various classes of phospholipids. Converts 1-acyl lysophosphatidylcholine (LPC) into phosphatidylcholine (PC) (LPCAT activity), 1-acyl lysophosphatidylserine (LPS) into phosphatidylserine (PS) (LPSAT activity) and 1-acyl lysophosphatidylethanolamine (LPE) into phosphatidylethanolamine (PE) (LPEAT activity). Favors polyunsaturated fatty acyl-CoAs as acyl donors compared to saturated fatty acyl-CoAs (PubMed:18287005, PubMed:25898003). Has higher activity for LPC acyl acceptors compared to LPEs and LPSs (PubMed:18287005). Can also transfer the fatty acyl chain from fatty acyl-CoA to 1-O-alkyl lysophospholipid or 1-O-alkenyl lysophospholipid with lower efficiency (PubMed:18287005). Acts as a major LPC O-acyltransferase in liver and intestine (PubMed:25898003, PubMed:26833026). As a component of the liver X receptor/NR1H3 or NR1H2 signaling pathway, mainly catalyzes the incorporation of arachidonate into PCs of endoplasmic reticulum (ER) membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (PubMed:25806685). Promotes processing of sterol regulatory protein SREBF1 in hepatocytes, likely by facilitating the translocation of SREBF1-SCAP complex from ER to the Golgi apparatus (PubMed:28846071). Participates in mechanisms by which the liver X receptor/NR1H3 or NR1H2 signaling pathway counteracts lipid-induced ER stress response and inflammation (PubMed:24206663). Down-regulates hepatic inflammation by limiting arachidonic acid availability for synthesis of inflammatory eicosanoids, such as prostaglandins (PubMed:24206663). In enterocytes, acts as a component of a gut-brain feedback loop that coordinates dietary lipid absorption and food intake. Regulates the abundance of PCs containing linoleate and arachidonate in enterocyte membranes, enabling passive diffusion of fatty acids and cholesterol across the membrane for efficient chylomicron assembly (PubMed:26833026). In the intestinal crypt, acts as a component of dietary-responsive phospholipid-cholesterol axis, regulating the biosynthesis of cholesterol and its mitogenic effects on intestinal stem cells (PubMed:29395055).|||Mutant mice are born at the expected Mendelian frequency, but none survives beyond day 2 due to an extensive triacylglycerol accumulation in enterocytes associated with very low blood glucose levels at birth (P1.5) (PubMed:25806685, PubMed:25898003). Conditional knockdown in intestine results in hyperproliferation of the intestinal crypt and increased susceptibility to intestinal tumorigenesis (PubMed:29395055).|||The di-lysine motif confers endoplasmic reticulum localization.|||Up-regulated in response to liver X receptor/NR1H3 or NR1H2 agonist GW3965 (PubMed:28846071, PubMed:25898003, PubMed:25806685, PubMed:24206663). Up-regulated in peritoneal macrophages upon exposure to 22(R)-hydroxycholesterol (PubMed:24206663). http://togogenome.org/gene/10090:Smarca4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J170|||http://purl.uniprot.org/uniprot/Q3TKT4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF2/RAD54 helicase family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible developmental- and tissue-specific combinations (Probable). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (PubMed:17640523). Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin. Component of SWI/SNF (GBAF) subcomplex, which includes at least BICRA or BICRAL (mutually exclusive), BRD9, SS18, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, SMARCC1/BAF155, and SMARCD1/BAF60A (PubMed:29374058). Component of the BAF53 complex, at least composed of BAF53A, RUVBL1, SMARCA4/BRG1/BAF190A, and TRRAP, which preferentially acetylates histone H4 (and H2A) within nucleosomes (By similarity). Component of the CREST-BRG1 complex, at least composed of SMARCA4/BRG1/BAF190A, SS18L1/CREST, HDAC1, RB1 and SP1 (By similarity). Interacts with PHF10/BAF45A (PubMed:17640523). Interacts with MYOG (PubMed:16424906). Interacts directly with IKFZ1; the interaction associates IKFZ1 with the BAF complex. Interacts with ZEB1 (via N-terminus). Interacts with NR3C1, PGR, SMARD1, TOPBP1 and ZMIM2/ZIMP7. Interacts with (via the bromodomain) with TERT; the interaction regulates Wnt-mediated signaling (By similarity). Interacts with KDM6A and KDM6B (PubMed:21095589). Interacts with TBX21 in a KDM6B-dependent manner (PubMed:21095589). Interacts with HNRNPU; this interaction occurs in embryonic stem cells and stimulates global Pol II-mediated transcription (PubMed:22162999). Interacts with ACTL6A (By similarity). Interacts with DLX1 (PubMed:26138476). Interacts with DPF2 (By similarity). Interacts with DPF3a (isoform 2 of DPF3/BAF45C) (By similarity). Interacts with HDGFL2 in a DPF3a-dependent manner (PubMed:32459350). May interact with ADNP2 (By similarity). Interacts with LETMD1 (via C-terminal); the interaction regulates transcriptional expression of thermogenic genes in brown adipose tissue (PubMed:34910916).|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP (By similarity). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development, a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role in regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues. Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1 (By similarity). Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2 (PubMed:26138476). Binds to RNA in a promiscuous manner (PubMed:26138476). Binding to RNAs including lncRNA Evf2 leads to inhibition of SMARCA4 ATPase and chromatin remodeling activities (PubMed:26138476). In brown adipose tissue, involved in the regulation of thermogenic genes expression (PubMed:34910916).|||Nucleus http://togogenome.org/gene/10090:Xlr4b ^@ http://purl.uniprot.org/uniprot/Q9JJQ7 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Plcg1 ^@ http://purl.uniprot.org/uniprot/Q62077 ^@ Activity Regulation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation on tyrosine residues.|||Interacts (via SH2 domain) with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated). Interacts with RALGPS1. Interacts (via SH2 domains) with VIL1 (phosphorylated at C-terminus tyrosine phosphorylation sites). Interacts (via SH2 domain) with RET (By similarity). Interacts with AGAP2 via its SH3 domain. Interacts with LAT (phosphorylated) upon TCR activation. Interacts (via SH3 domain) with the Pro-rich domain of TNK1. Associates with BLNK, VAV1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with CBLB in activated T-cells; which inhibits phosphorylation. Interacts with SHB. Interacts (via SH3 domain) with the Arg/Gly-rich-flanked Pro-rich domains of KHDRBS1/SAM68. This interaction is selectively regulated by arginine methylation of KHDRBS1/SAM68. Interacts with INPP5D/SHIP1, THEMIS and CLNK. Interacts with FLT4 and KIT. Interacts with AXL (By similarity). Interacts with SYK; activates PLCG1 (By similarity). Interacts with FLT1 (tyrosine-phosphorylated). Interacts (via SH2 domain) with PDGFRA and PDGFRB (tyrosine phosphorylated). Interacts with PIP5K1C. Interacts with NTRK1 and NTRK2 (phosphorylated upon ligand-binding). Interacts with TESPA1 (By similarity). Interacts with GRB2, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1.|||Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin reorganization and cell migration (By similarity).|||The SH3 domain mediates interaction with RALGPS1 (By similarity). The SH3 domain also mediates interaction with CLNK.|||Tyrosine phosphorylated in response to signaling via activated FLT3, KIT and PDGFRA (By similarity). Tyrosine phosphorylated by activated FGFR1, FGFR2, FGFR3 and FGFR4. Tyrosine phosphorylated by activated FLT1 and KDR. Tyrosine phosphorylated by activated PDGFRB. The receptor-mediated activation of PLCG1 involves its phosphorylation by tyrosine kinases in response to ligation of a variety of growth factor receptors and immune system receptors. For instance, SYK phosphorylates and activates PLCG1 in response to ligation of the B-cell receptor. Phosphorylated by ITK and TXK on Tyr-783 upon TCR activation in T-cells. May be dephosphorylated by PTPRJ (By similarity).|||Ubiquitinated by CBLB in activated T-cells.|||lamellipodium|||ruffle http://togogenome.org/gene/10090:Cutal ^@ http://purl.uniprot.org/uniprot/A0A0J9YUN0|||http://purl.uniprot.org/uniprot/Q9D1U5 ^@ Similarity|||Subunit ^@ Belongs to the CutA family.|||Homotrimer. http://togogenome.org/gene/10090:Ppp2r5e ^@ http://purl.uniprot.org/uniprot/Q61151 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphatase 2A regulatory subunit B56 family.|||Cytoplasm|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1. Found in a complex with at least ARL2, PPP2CB; PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity).|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Interacts with cyclin G in vitro. http://togogenome.org/gene/10090:Aadacl2 ^@ http://purl.uniprot.org/uniprot/B2RWD2 ^@ Similarity ^@ Belongs to the 'GDXG' lipolytic enzyme family. http://togogenome.org/gene/10090:Prl2a1 ^@ http://purl.uniprot.org/uniprot/A0A0M5HDY7|||http://purl.uniprot.org/uniprot/Q9JHK0 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed specifically in the placenta. Expression restricted to the junctional zone of the chorioallantoic placenta.|||Secreted http://togogenome.org/gene/10090:Nadsyn1 ^@ http://purl.uniprot.org/uniprot/Q711T7 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source.|||Highly expressed in small intestine, kidney, liver and testis. Weakly expressed in skeletal muscle, spleen, lung, heart and brain.|||Homohexamer.|||In the C-terminal section; belongs to the NAD synthetase family. http://togogenome.org/gene/10090:Smim20 ^@ http://purl.uniprot.org/uniprot/D3Z7Q2 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By fatty acids, specifically palmitate, docosahexanoic acid and oleate.|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly (By similarity). Promotes the progression of complex assembly after the association of MT-CO1/COX1 with COX4I1 and COX6C (By similarity). Chaperone-like assembly factor required to stabilize newly synthesized MT-CO1/COX1 and to prevent its premature turnover (By similarity).|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14 (By similarity). Interacts with COA3/MITRAC12 and COX4I1 (By similarity). Directly interacts with newly synthesized MT-CO1/COX1 (By similarity).|||Highly expressed in the hypothalamus, the spinal cord, and sensory ganglia (at protein level) (PubMed:23912037, PubMed:26415767). Also expressed on in the epidermis and dermis layers of the skin (at protein level) (PubMed:26415767). Expressed in preadipocytes and adipocytes (at protein level) (PubMed:30251651). Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level) (PubMed:30933929).|||Mitochondrion inner membrane|||Peptide involved in a broad spectrum of regulatory functions (PubMed:25687846, PubMed:26505917, PubMed:27268078). Is a ligand for GPR173 (By similarity). As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone (PubMed:27268078). More specifically, it regulates the expression of transcription factors CEBPB and POU2F1/OCT1 through the cAMP-PKA signaling pathway, which subsequently regulate the expression of GNRHR and KISS1 (PubMed:27268078). Plays a protective role in memory retention through activation of GNRHR (PubMed:26505917). Regulates the secretion of AVP by hypothalamic neurons (By similarity). Plays a role in the transduction of the itch sensation (PubMed:26415767). Induces anxiolytic effects, reducing behavior associated with anxiety (PubMed:25687846). Regulates food intake as well as satiation and satiety by increasing Nucb2 expression in neurons (By similarity). In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR (PubMed:30933929). It also increases the production of estradiol (E2) (PubMed:30933929). In the heart, it regulates contractility and relaxation by activating the AKT1-NOS3 and MAPK1-MAPK3 signaling pathways (By similarity). It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways (By similarity). Stimulates the proliferation and differentiation of preadipocytes (PubMed:30251651). In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS through activation of the MAPK1-MAPK3 signaling pathways (PubMed:31422055).|||Secreted http://togogenome.org/gene/10090:Pknox2 ^@ http://purl.uniprot.org/uniprot/Q8BG99 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TALE/MEIS homeobox family.|||Nucleus http://togogenome.org/gene/10090:Ypel5 ^@ http://purl.uniprot.org/uniprot/P62700 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the yippee family.|||Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (By similarity). Required for normal cell proliferation (By similarity).|||Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with RANBP9 and RANBP10.|||Midbody|||Nucleus|||centrosome|||spindle pole http://togogenome.org/gene/10090:Cldn34c4 ^@ http://purl.uniprot.org/uniprot/A2ANA3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Desi2 ^@ http://purl.uniprot.org/uniprot/Q8BIB9|||http://purl.uniprot.org/uniprot/Q9D291 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DeSI family.|||Cytoplasm|||Has deubiquitinating activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Deubiquitinates 'Lys-48'-linked polyubiquitination of RPS7 leading to its stabilization.|||Interacts with RPS7.|||Widely expressed. http://togogenome.org/gene/10090:Cntn5 ^@ http://purl.uniprot.org/uniprot/P68500 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. Contactin family.|||Cell membrane|||Contactins mediate cell surface interactions during nervous system development. Has some neurite outgrowth-promoting activity in the cerebral cortical neurons but not in hippocampal neurons (By similarity). Involved in neuronal activity in the auditory system.|||Expressed in the nervous system. Preferentially expressed in the central auditory pathways.|||Interacts with PTPRG.|||Specifically expressed in the postnatal nervous system, reaching a maximum level at 3 weeks postnatal. http://togogenome.org/gene/10090:Gcsh ^@ http://purl.uniprot.org/uniprot/Q91WK5 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GcvH family.|||Binds 1 lipoyl cofactor covalently.|||Mitochondrion|||The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST) (By similarity).|||The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH). Interacts with GLDC (By similarity). http://togogenome.org/gene/10090:Slc16a11 ^@ http://purl.uniprot.org/uniprot/Q5NC32|||http://purl.uniprot.org/uniprot/Q9JJC0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with isoform 2 of BSG.|||Membrane|||Proton-linked monocarboxylate transporter. It catalyzes the transport of pyruvate across the plasma membrane. Probably involved in hepatic lipid metabolism: overexpression results in an increase of triacylglycerol(TAG) levels, small increases in intracellular diacylglycerols and decreases in lysophosphatidylcholine, cholesterol ester and sphingomyelin lipids. http://togogenome.org/gene/10090:Pcnt ^@ http://purl.uniprot.org/uniprot/A0A1W2P737|||http://purl.uniprot.org/uniprot/F8VPV0|||http://purl.uniprot.org/uniprot/P48725|||http://purl.uniprot.org/uniprot/Q3TQR8|||http://purl.uniprot.org/uniprot/Q80U10|||http://purl.uniprot.org/uniprot/Q8CDL2 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cleaved during mitotis which leads to removal of CDK5RAP2 from the centrosome and promotes centriole disengagement and subsequent centriole separation. The C-terminal fragment is rapidly degraded following cleavage.|||Composed of a coiled-coil central region flanked by non-helical N- and C-terminals.|||Expressed in embryo at 17 dpc (at protein level). Expressed in embryos at 7, 11, 15 and 17 dpc. Strongly expressed in brain tissues at early stages of development.|||Expressed in heart and lung (at protein level). Expressed in kidney, thymus, liver, brain, muscle, testis, spleen, lung and heart.|||Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome.|||Interacts with DISC1 and PCM1. Binds calmodulin. Interacts with CEP131 (By similarity). Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of PCNT and CDK5RAP2 (PubMed:20471352). Interacts with CHD3 (PubMed:17626165). Interacts with CHD4; the interaction regulates centrosome integrity (PubMed:17626165). Interacts with NEK2 (By similarity). Interacts with CCDC13 (By similarity). Interacts with CEP68 (By similarity). Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome (By similarity).|||Ubiquitinated by TRIM43; leading to proteasomal degradation.|||centrosome http://togogenome.org/gene/10090:Tnnt3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1A8|||http://purl.uniprot.org/uniprot/A0A0R4J1B0|||http://purl.uniprot.org/uniprot/A0A0R4J1B1|||http://purl.uniprot.org/uniprot/A2A6H6|||http://purl.uniprot.org/uniprot/A2A6I0|||http://purl.uniprot.org/uniprot/A2A6I3|||http://purl.uniprot.org/uniprot/A2A6I5|||http://purl.uniprot.org/uniprot/A2A6I8|||http://purl.uniprot.org/uniprot/A2A6J0|||http://purl.uniprot.org/uniprot/A2A6J1|||http://purl.uniprot.org/uniprot/Q9QZ47|||http://purl.uniprot.org/uniprot/Z4YJU0|||http://purl.uniprot.org/uniprot/Z4YKD9|||http://purl.uniprot.org/uniprot/Z4YKF8|||http://purl.uniprot.org/uniprot/Z4YKG3|||http://purl.uniprot.org/uniprot/Z4YKG8|||http://purl.uniprot.org/uniprot/Z4YNB2 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the troponin T family.|||Embryo and neonate express predominantly acidic isoforms while all adult isoforms are basic. Only one isoform, B2e17, is found in both embryo/neonate and adult. A transition from high to low molecular weight isoforms is also seen during postnatal development.|||Expressed predominantly in skeletal muscle.|||Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. http://togogenome.org/gene/10090:Itgb8 ^@ http://purl.uniprot.org/uniprot/Q0VBD0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin beta chain family.|||Cell membrane|||Embryonic or perinatal lethality caused profound defects in vascular development (PubMed:12050137). More than half embryos die at midgestation, with evidence of insufficient vascularization of the placenta and yolk sac (PubMed:12050137). Surviving embryos die shortly after birth with extensive intracerebral hemorrhage (PubMed:12050137). Conditional deletion in the neuroepithelium results in bilateral hemorrhage at in neonates caused by endothelial cell abnormalities in the developing cortex (PubMed:16251442).|||Expressed in endodermal cells surrounding endothelium in the yolk sac and in periventricular cells of the neuroepithelium in the brain.|||Heterodimer of an alpha and a beta subunit (PubMed:25127859). Beta-8 (ITGB8) associates with alpha-V (ITGAV) to form ITGAV:ITGB8 (PubMed:25127859). ITGAV:ITGB8 interacts with TGFB1 (PubMed:25127859).|||Integrin alpha-V:beta-8 (ITGAV:ITGB8) is a receptor for fibronectin (By similarity). It recognizes the sequence R-G-D in its ligands (By similarity). Integrin alpha-V:beta-6 (ITGAV:ITGB6) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation on the surface of activated regulatory T-cells (Tregs) (PubMed:25127859). Required during vasculogenesis (PubMed:12050137, PubMed:16251442).|||The VWFA domain (or beta I domain) contains two cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS) and the metal ion-dependent adhesion site (MIDAS). Unlike in the other beta integrins, the cation-binding site adjacent MIDAS site (ADMIDAS) in ITGB8 is not functional due to the presence of two Asn residues instead of 2 Asp residues. This domain is also part of the ligand-binding site. http://togogenome.org/gene/10090:Cenpn ^@ http://purl.uniprot.org/uniprot/Q9CZW2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-N/CHL4 family.|||Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.|||Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. Interacts directly with CENPA. Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1.|||Nucleus|||centromere|||kinetochore http://togogenome.org/gene/10090:Lcn9 ^@ http://purl.uniprot.org/uniprot/Q9D267 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calycin superfamily. Lipocalin family.|||Expressed in epididymis. Not detected in all other tissues tested.|||First detected after 3 weeks postnatal development.|||Secreted http://togogenome.org/gene/10090:Or6c217 ^@ http://purl.uniprot.org/uniprot/Q8VFU0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:C6 ^@ http://purl.uniprot.org/uniprot/Q91X70 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the complement C6/C7/C8/C9 family.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Secreted http://togogenome.org/gene/10090:Suds3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J243|||http://purl.uniprot.org/uniprot/Q8BR65 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SDS3 family.|||Expressed in all newborn tissues tested, including brain, kidney and liver.|||Interacts with HCFC1 (By similarity). Homodimer. Component of the SIN3 histone deacetylase (HDAC) corepressor complex. Interacts with SIN3A. Interaction with SIN3B enhances the interaction between SIN3B and HDAC1 to form a complex. Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2. Interacts with USP17L2; the interaction is direct (By similarity). Interacts with FOXK2 (By similarity).|||Nucleus|||Polyubiquitinated. 'Lys-63'-polyubiquitinated SUDS3 positively regulates histone deacetylation. Regulated through deubiquitination by USP17L2/USP17 that cleaves 'Lys-63'-linked ubiquitin chains (By similarity).|||Regulatory protein which represses transcription and augments histone deacetylase activity of HDAC1. May have a potential role in tumor suppressor pathways through regulation of apoptosis. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes (By similarity).|||The C-terminus is involved in transcriptional repression by HDAC-independent mechanisms. http://togogenome.org/gene/10090:Wfdc8 ^@ http://purl.uniprot.org/uniprot/Q4KUS1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Praf2 ^@ http://purl.uniprot.org/uniprot/Q9JIG8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRA1 family.|||Endosome membrane|||Interacts with CCR5 and GDE1.|||May be involved in ER/Golgi transport and vesicular traffic. Plays a proapoptotic role in cerulenin-induced neuroblastoma apoptosis (By similarity). http://togogenome.org/gene/10090:Or6c88 ^@ http://purl.uniprot.org/uniprot/Q8VF26 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pip4p2 ^@ http://purl.uniprot.org/uniprot/Q9CZX7 ^@ Function|||Subcellular Location Annotation ^@ Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P) (By similarity). Does not hydrolyze phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-bisphosphate, inositol 3,5-bisphosphate, inositol 3,4-bisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate (By similarity). Negatively regulates the phagocytosis of large particles by reducing phagosomal phosphatidylinositol 4,5-bisphosphate accumulation during cup formation (PubMed:29378918).|||Cell membrane|||Late endosome membrane|||Lysosome membrane|||phagosome membrane http://togogenome.org/gene/10090:Stxbp5 ^@ http://purl.uniprot.org/uniprot/D3Z079 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat L(2)GL family.|||Cell membrane|||Cytoplasm|||Membrane http://togogenome.org/gene/10090:Tex19.1 ^@ http://purl.uniprot.org/uniprot/Q99MV2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in early embryo and is later limited to the germ line. Expressed in the ectoderm and then in primordial germ cells (PGCs). Expressed in testis from 13.5 dpc to adulthood in gonocytes and spermatocytes. Also present in the developing and adult ovary as well as in the placenta and its precursor tissue, the ectoplacental cone.|||Expressed in testis, placenta and ovary. Expressed in pluripotent stem cells. In testis, expression is highest in mitotic spermatogonia, decreases as spermatocytes progress through meiosis, and is present at low levels in round spermatids (at protein level).|||Expression is down-regulated by DAZL protein, which binds to 3'UTR of Tex19.1 mRNAs and probably represses its translation.|||Interacts with UBR2; does not lead to Tex19.1 degradation and stabilizes it (PubMed:21103378). Interacts with piRNA-associated proteins DDX4, EDC4, MAEL, PIWIL1, PIWIL2, RANBP9 and TDRD6 (PubMed:28254886). Interacts with L1RE1 (PubMed:28806172).|||Mutant embryos exhibit intra-uterine growth retardation and have small placentas due to a reduction in the number of spongiotrophoblast, glycogen trophoblast and sinusoidal trophoblast giant cells. They show an incomplete penetrance of embryonic lethality preferentially affecting females. Knockout have heterogeneous spermatogenic defects and testicular degeneration leading to infertility in the most severe cases. During spermatogenesis, mutants show impaired recombination during leptotene stage of meiotic prophase leading to chromosome asynapsis. Knockout females are fertile (PubMed:23364048, PubMed:23674551, PubMed:18802469, PubMed:21103378, PubMed:28708824). Males deficient for both Tex19.1 and Tex19.2 have impaired spermatogenesis, small testes and are infertile. They show vacuolization and seminiferous epithelium degeneration as early as P16. They have defects in meiotic chromosome synapsis, persistence of DNA double-strand breaks during meiosis, lack of post-meiotic germ cell and up-regulation of MMERVK10C retrotransposon expression. Number of females deficient for both for Tex19.1 and Tex19.2 that survive 2 weeks or more is reduced compared to males. Females display normal fertility. Surviving mutants do not present gross somatic abnormalities (PubMed:28254886).|||Required during spermatogenesis and placenta development, participating in the repression of retrotransposable elements and preventing their mobilization (PubMed:18802469, PubMed:21103378, PubMed:23364048, PubMed:23674551, PubMed:28254886). With its paralog, Tex19.2, collaborates with the Piwi-interacting RNA (piRNA) pathway, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins. Interacts with Piwi proteins and directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:28254886). Also during spermatogenesis, promotes, with UBR2, SPO11-dependent meiotic recombination (PubMed:28708824). Interacts with LINE-1 retrotransposon encoded LIRE1, stimulates LIRE1 polyubiquitination, mediated by UBR2, and degradation, inhibiting LINE-1 retrotransposon mobilization (PubMed:28806172). http://togogenome.org/gene/10090:Hars ^@ http://purl.uniprot.org/uniprot/Q61035 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP). Plays a role in axon guidance.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Surf1 ^@ http://purl.uniprot.org/uniprot/I6L9E0|||http://purl.uniprot.org/uniprot/P09925 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SURF1 family.|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex (By similarity). Regulates cytochrome c oxidase assembly (PubMed:17210671, PubMed:23838831, PubMed:24911525).|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.|||Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14. Interacts with COA3.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mitochondrion inner membrane|||Mitochondrion membrane|||Results in smaller animals with mild decreased motor skills, enhanced working spatial and recognition memory, and increased longevity (PubMed:17210671, PubMed:23838831, PubMed:24911525). Increases global and regional cerebral blood flow (PubMed:23838831). Increases lactate levels in blood and brain, and increases glucose consumption in the brain (PubMed:17210671, PubMed:23838831, PubMed:24911525). Increases hydrogen peroxide production and succinate dehydrogenase (SDH) activity, but decreases COX activity and respiration (PubMed:17210671, PubMed:21167962, PubMed:23838831, PubMed:24911525). In the brain, increases Hif1a and phosphorylated cyclic AMP response element-binding protein levels (PubMed:23838831). In the brain, increases resistance to calcium-related excitotoxic brain damage (PubMed:17210671). In skeletal muscles, results in mitochondrial unfolded protein response (PubMed:24911525). In the heart, results in elevated Nfe2l2 and Hmox1 expression (PubMed:24911525). Primary cultures of mutant neuronal cells show reduced sensitivity to glutamate-induced cytosolic calcium signal and impaired mitochondrial calcium uptake without changing the mitochondrial structure and membrane potential (PubMed:17210671). Primary cultures of phrenic and central vagus nerves show increased respiratory frequency and altered response to systemic hypoxia and hypercapnia (PubMed:21167962). http://togogenome.org/gene/10090:Nmur1 ^@ http://purl.uniprot.org/uniprot/O55040 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for the neuromedin-U and neuromedin-S neuropeptides.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Med19 ^@ http://purl.uniprot.org/uniprot/Q8C1S0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 19 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gm14459 ^@ http://purl.uniprot.org/uniprot/A2BI73 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Sbds ^@ http://purl.uniprot.org/uniprot/P70122 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with the 60S ribosomal subunit. Interacts with NPM1, RPA1 and PRKDC. May interact with NIP7. Found in a complex consisting of the 60S ribosomal subunit, SBDS and EFL1. Interacts with CLN3 (By similarity).|||Belongs to the SDO1/SBDS family.|||Cytoplasm|||Detected in adult liver, brain, heart, spleen, pancreas, kidney, lung and testis (at protein level). Detected in heart, brain, lung, liver, kidney and testis.|||Embryonic lethality. Embryos cease to develop prior to 6.5 dpc. Reduced assembly of 60S ribosomes and accumulation of halfmer ribosomes.|||Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation (By similarity).|||nucleolus|||nucleoplasm|||spindle http://togogenome.org/gene/10090:Nars ^@ http://purl.uniprot.org/uniprot/Q8BP47 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the attachment of asparagine to tRNA(Asn) in a two-step reaction: asparagine is first activated by ATP to form Asn-AMP and then transferred to the acceptor end of tRNA(Asn). In addition to its essential role in protein synthesis, acts as a signaling molecule that induced migration of CCR3-expressing cells. Has an essential role in the development of the cerebral cortex, being required for proper proliferation of radial glial cells.|||Cytoplasm|||Homodimer.|||The N-terminal domain (1-77) recruits and activates specific immune cells by interacting with CCR3-expressing cells. http://togogenome.org/gene/10090:Cdip1 ^@ http://purl.uniprot.org/uniprot/Q9DB75 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Acts as an important p53/TP53-apoptotic effector. Regulates TNF-alpha-mediated apoptosis in a p53/TP53-dependent manner (By similarity).|||Belongs to the CDIP1/LITAF family.|||Late endosome membrane|||Lysosome membrane|||The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes. http://togogenome.org/gene/10090:Slc6a13 ^@ http://purl.uniprot.org/uniprot/P31649 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in neonatal brain, but not in adult brain.|||Basolateral cell membrane|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A13 subfamily.|||Cell membrane|||Expressed at high levels in liver, followed by kidney and leptomeninges, and very low levels in the cerebellum (at protein level). In the brain, detected in some blood vessels (at protein level). In the kidney, expressed in the cortex, including parts of the proximal tubules, but not in the medulla (at protein level). In the liver, highest expression in periportal hepatocytes, with highest density at the vascular side (at protein level). Also detected at low levels in other organs, including skeletal muscle.|||Gamma-aminobutyric acid (GABA) transport is inhibited by beta-alanine, taurine, hypotaurine, beta-guanidinopropionic acid, 2,3-diaminopropionic acid, guvacine and nipecotic acid (PubMed:8420981, PubMed:22896705). Beta-alanine transport is inhibited by GABA (PubMed:8420981). Taurine transport is inhibited by GABA, beta-alanine, SNAP-5114, nigericin, nipecotic acid and ouabain (PubMed:22896705).|||Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:8420981, PubMed:22896705, PubMed:30270321). Can also mediate transport of beta-alanine, taurine and hypotaurine and is the major taurine transporter in hepatocytes (PubMed:8420981, PubMed:22896705, PubMed:30270321).|||Mutant animals are born at the expected Mendelian ratio. They appear normal, fertile, with a normal life span. Tissue taurine levels are altered, with 50% decrease in the liver and 20% increase in the brain. http://togogenome.org/gene/10090:Pdha1 ^@ http://purl.uniprot.org/uniprot/P35486|||http://purl.uniprot.org/uniprot/Q3UFJ3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylation alters the phosphorylation pattern. Deacetylated by SIRT3.|||Complete embryonic lethality. Normal embryonic development ceases about 9.5 dpc. Conditional gene disruption in the heart causes death shortly after weaning in male mice fed normal chow, while mice on high fat diet survive, but develop left ventricular hypertrophy, due to impaired glucose and energy metabolism in the heart. Likewise, conditional gene disruption in pancreas islet beta cells disrupts normal insulin secretion in response to glucose stimuli, while conditional gene disruption in oocytes causes reduced ATP levels and thereby prevents normal meiosis during oocyte maturation.|||Heterotetramer of two PDHA1 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (By similarity).|||In all tissues, but in very low amount in testis.|||Mitochondrion matrix|||Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Phosphorylation at Ser-293 interferes with access to active site, and thereby inactivates the enzyme. Dephosphorylation at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required for reactivation (By similarity).|||Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA1; it is reactivated by dephosphorylation.|||The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. http://togogenome.org/gene/10090:AU040320 ^@ http://purl.uniprot.org/uniprot/Q8K135 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Acts as a receptor for adeno-associated virus and is involved in adeno-associated virus infection through endocytosis system.|||Cell membrane|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasmic granule membrane|||Golgi apparatus membrane|||Homozygous knockout mice Kiaa0319l are normal.|||Interacts with RTN4R.|||N-glycosylated.|||Possible role in axon guidance through interaction with RTN4R.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Mblac2 ^@ http://purl.uniprot.org/uniprot/Q8BL86 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Has an acyl-CoA thioesterase activity towards the long chain fatty acyl-CoA thioester palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA). Displays a substrate preference for fatty acyl-CoAs with chain-lengths C12-C18.|||Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.|||Binds 2 Zn(2+) ions per subunit.|||Cell membrane|||Endoplasmic reticulum membrane|||Palmitoylated on Cys-254 by ZDHHC20. http://togogenome.org/gene/10090:Or52d3 ^@ http://purl.uniprot.org/uniprot/E9PVA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Krt84 ^@ http://purl.uniprot.org/uniprot/Q99M73 ^@ Induction|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||In skin, only expressed in the suprabasal cells of tail scale epidermis. Suprabasally expressed in stratified squamous epithelia and also in the posterior unit of the complex filiform papillae of tongue. Expressed in rare anatomical sites in which an orthokeratinized stratum corneum would be too soft and a hard keratinized structure would be too rigid to meet the functional requirement of the respective epithelia.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).|||mRNA synthesis is suppressed during retinoic acid-mediated orthokeratotic conversion of tail scale epidermis. http://togogenome.org/gene/10090:Ift80 ^@ http://purl.uniprot.org/uniprot/Q8K057 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:19253336, PubMed:23810713). Interacts with IFT88 (PubMed:19253336). Interacts with IFT57 and IFT70B (PubMed:23810713).|||Component of the intraflagellar transport (IFT) complex B, which is essential for the development and maintenance of motile and sensory cilia.|||Cytoplasm|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Arl11 ^@ http://purl.uniprot.org/uniprot/Q6P3A9 ^@ Function|||Similarity ^@ Belongs to the small GTPase superfamily. Arf family.|||May play a role in apoptosis. May act as a tumor suppressor (By similarity). http://togogenome.org/gene/10090:Edem3 ^@ http://purl.uniprot.org/uniprot/A0A087WQK5|||http://purl.uniprot.org/uniprot/A0A087WR24|||http://purl.uniprot.org/uniprot/B7ZNP0|||http://purl.uniprot.org/uniprot/Q2HXL6 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 47 family.|||Contains a protease-associated domain of unknown function.|||Endoplasmic reticulum lumen|||Involved in endoplasmic reticulum-associated degradation (ERAD). Accelerates the glycoprotein ERAD by proteasomes, by catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 in the N-glycans. May also participate in mannose trimming from all glycoproteins and not just misfolded ones targeted to ERAD (PubMed:34143952). May have alpha 1,2-mannosidase activity.|||N-glycosylated.|||Slightly increased by endoplasmic reticulum stress.|||The knockout mice show largely skewed ratios of homozygous knockout pups versus heterozygous and wild-type pups. However knockout animals do not present with any obvious phenotype, only subtle changes, such as reduced weight of brains and body, as well as significantly increased abundance of circulating Man8GlcNAc2 and Man9GlcNAc2 in the plasma.|||Widely expressed. Expressed at higher level in liver, heart and kidney. http://togogenome.org/gene/10090:Cfc1 ^@ http://purl.uniprot.org/uniprot/P97766 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.|||Cell membrane|||Expressed during gastrulation (from 6.5 dpc to 11 dpc) in two spatial domains that correspond to the axial and lateral mesoderm. In the first domain expression is progressively localized to the anterior primitive streak, the head process, and the node and notochordal. In the second domain, expression is initially concentrated in the lateral region of the egg cylinder, and is later found circumferentially in the intermediate and lateral plate mesoderm. Furthermore, the expression can also be detected at the early head-fold stage in the midline neuroectoderm, and consequently is an early marker for the prospective floor plate of the neural tube. Expression ceases at the end of gastrulation, and has not been observed in later embryonic stages.|||N-glycosylated.|||No expressed in adult tissues.|||Nodal coreceptor involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation.|||Positional defects in internal organs. The lung presents a right pulmonary isomerism. The stomach is located on either the left or the right and the spleen is small and has an abnormal shape. The apex of the heart pointed to the right or left. In addition malpositioning of heart outflow tracts is observed, the aorta is connected to the right ventricle and emerged from the heart in a ventral position and to the right of the pulmonary artery. This one is connected to either the left or the right ventricle.|||Secreted http://togogenome.org/gene/10090:Rundc3b ^@ http://purl.uniprot.org/uniprot/D3YUQ5|||http://purl.uniprot.org/uniprot/Q6PDC0 ^@ Similarity|||Subunit ^@ Belongs to the RUNDC3 family.|||Interacts with RAP2A. http://togogenome.org/gene/10090:Dmac2 ^@ http://purl.uniprot.org/uniprot/Q9D7K5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP synthase subunit s family.|||Interacts with incompletely assembled mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).|||Mitochondrion|||Required for the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Involved in the assembly of the distal region of complex I. http://togogenome.org/gene/10090:Tmem120a ^@ http://purl.uniprot.org/uniprot/Q8C1E7 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM120 family.|||Cell membrane|||Embryonic lethality (PubMed:32084332). Conditional knockout in nociceptors decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli (PubMed:32084332).|||Homooligomer and heterooligomer with TMEM120B.|||Ion channel involved in sensing mechanical pain (PubMed:32084332). Contributes to mechanosensitive currents in nocireceptors and detecting mechanical pain stimuli (PubMed:32084332). May also be required for efficient adipogenesis (PubMed:26024229).|||Nucleus inner membrane|||TACAN means movement in Farsi.|||Up-regulated during adipocyte differentiation.|||Widely expressed, with higher expression in the heart, kidneys, colon and sensory neurons of the dorsal root ganglia (PubMed:32084332). Expressed in nociceptors (PubMed:32084332). Highly expressed in white adipose tissue (at protein level) (PubMed:26024229). Highly expressed in brown adipose tissue and expressed at low levels in liver (PubMed:26024229). http://togogenome.org/gene/10090:Slc19a3 ^@ http://purl.uniprot.org/uniprot/Q99PL8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.|||High expression in kidney, brain, lung and small intestine (PubMed:11136550). Detected in pancreatic acinar cells (at protein level) (PubMed:22194418). Also expressed strongly in pancreatic islet cells (PubMed:22194418).|||High-affinity transporter for the intake of thiamine (PubMed:22194418, PubMed:35512554, PubMed:35724964). Unlike the human ortholog, lacks H(+)-dependent pyridoxine transport activity due to an absence of seven critical amino-acids required for pyridoxine transport (PubMed:35512554, PubMed:35724964).|||Membrane|||Thiamine uptake by pancreatic acinar cells from knockout mice was found to be significantly lower than uptake by pancreatic acinar cells of the wild-type littermates. http://togogenome.org/gene/10090:Fam83b ^@ http://purl.uniprot.org/uniprot/Q0VBM2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM83 family.|||Cytoplasm|||Interacts with EGFR; positively regulates EGFR inducing its autophosphorylation in absence of stimulation by EGF. Interacts with RAF1; displaces 14-3-3 proteins from RAF1 and activates RAF1 within the RAS/MAPK signaling cascade. Interacts with AKT1, PIK3CA and PIK3R1; activates the PI3K/AKT signaling cascade.|||Membrane|||Probable proto-oncogene that functions in the epidermal growth factor receptor/EGFR signaling pathway. Activates both the EGFR itself and downstream RAS/MAPK and PI3K/AKT/TOR signaling cascades. http://togogenome.org/gene/10090:Ipo4 ^@ http://purl.uniprot.org/uniprot/Q8VI75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the importin beta family.|||Cytoplasm|||Found in a cytosolic complex with ASF1 (ASF1A or ASF1B) and histones H3 and H4.|||Nuclear transport receptor that mediates nuclear import of proteins, such as histones, RPS3A, TNP2 and VDR. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates the nuclear import of the histone H3-H4 dimer when in complex with ASF1 (ASF1A or ASF1B). Mediates the ligand-independent nuclear import of vitamin D receptor (VDR).|||Nucleus http://togogenome.org/gene/10090:1600014C10Rik ^@ http://purl.uniprot.org/uniprot/Q8WUR0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the C19orf12 family.|||Endoplasmic reticulum|||Mitochondrion|||Mitochondrion membrane|||cytosol http://togogenome.org/gene/10090:Adgrd1 ^@ http://purl.uniprot.org/uniprot/B2RXV6|||http://purl.uniprot.org/uniprot/Q80T32 ^@ Caution|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ A short peptide sequence (termed the Stachel sequence) in the C-terminal part of the extra-cellular domain (ECD) functions as a tethered agonist. Upon structural changes within the ECD, e.g. due to extracellular ligand binding or mechanical movements, this intramolecular agonist is exposed to the 7TM domain, triggering G-protein activation.|||Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Orphan receptor. Signals via G(s)-alpha family of G-proteins.|||The N-terminal domain and autocatalytic activity of ADGRD1 at the GPCR proteolysis site (GPS) are not required for G-protein coupling activity. http://togogenome.org/gene/10090:A530016L24Rik ^@ http://purl.uniprot.org/uniprot/Q8BNX7 ^@ Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Highly up-regulated during 3T3-L1 cell differentiation into adipocytes. In vivo, down-regulated by fasting in both white and brown adipose tissues. Reduced in white adipose tissue in obese animals.|||Predominantly expressed in white adipose tissue (at protein level) and brown adipose tissue. Also detected in heart. http://togogenome.org/gene/10090:Rpl27 ^@ http://purl.uniprot.org/uniprot/P61358|||http://purl.uniprot.org/uniprot/Q5BLJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eL27 family.|||Component of the large ribosomal subunit (PubMed:36517592). Interacts with RRP1B (By similarity). Interacts with DHX33 (PubMed:26100019).|||Component of the large ribosomal subunit (PubMed:36517592). Required for proper rRNA processing and maturation of 28S and 5.8S rRNAs (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Rough endoplasmic reticulum|||cytosol http://togogenome.org/gene/10090:Col1a1 ^@ http://purl.uniprot.org/uniprot/P11087 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the fibrillar collagen family.|||Contains 3-hydroxyproline at a few sites. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.|||Contains mostly 4-hydroxyproline. Proline residues at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Expressed in early bell stage dental mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588). Expressed in bell stage dental mesenchymal cells at 17.5 dpc (PubMed:29148101).|||Forms the fibrils of tendon, ligaments and bones. In bones the fibrils are mineralized with calcium hydroxyapatite.|||Lysine residues at the third position of the tripeptide repeating unit (G-X-Y) are 5-hydroxylated in some or all of the chains.|||O-glycosylated on hydroxylated lysine residues. The O-linked glycan consists of a Glc-Gal disaccharide.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||Trimers of one alpha 2(I) and two alpha 1(I) chains. Interacts with MRC2. Interacts with TRAM2. Interacts with MFAP4 in a Ca (2+)-dependent manner.|||Type I collagen is a member of group I collagen (fibrillar forming collagen).|||extracellular matrix http://togogenome.org/gene/10090:Prr23a2 ^@ http://purl.uniprot.org/uniprot/D3YWX5 ^@ Similarity ^@ Belongs to the PRR23 family. http://togogenome.org/gene/10090:Ilvbl ^@ http://purl.uniprot.org/uniprot/Q8BU33 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TPP enzyme family.|||Binds 1 Mg(2+) ion per subunit.|||Binds 1 thiamine pyrophosphate per subunit.|||Endoplasmic reticulum 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner. Involved in the phytosphingosine degradation pathway.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Defa37 ^@ http://purl.uniprot.org/uniprot/K9J724 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Csnk1g1 ^@ http://purl.uniprot.org/uniprot/A0A0U1RNW0|||http://purl.uniprot.org/uniprot/A0A0U1RPD7|||http://purl.uniprot.org/uniprot/Q6P2B2|||http://purl.uniprot.org/uniprot/Q8BTH8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated.|||Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.|||Cytoplasm|||Expressed in both the striatum and the neocortex.|||Monomer.|||Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CLSPN (By similarity). Regulates fast synaptic transmission mediated by glutamate. http://togogenome.org/gene/10090:Tgds ^@ http://purl.uniprot.org/uniprot/Q8VDR7 ^@ Similarity ^@ Belongs to the NAD(P)-dependent epimerase/dehydratase family. dTDP-glucose dehydratase subfamily. http://togogenome.org/gene/10090:Rgs4 ^@ http://purl.uniprot.org/uniprot/O08899|||http://purl.uniprot.org/uniprot/Q5D078 ^@ Function|||PTM|||Tissue Specificity ^@ Either Cys-2 or Cys-12 or both are palmitoylated.|||Expressed at high levels in brain, moderately low levels in heart, and very low levels in lung, liver, and skeletal muscle.|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(z)-alpha is inhibited by phosphorylation of the G-protein. Activity on G(z)-alpha and G(i)-alpha-1 is inhibited by palmitoylation of the G-protein (By similarity).|||Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(z)-alpha is inhibited by phosphorylation of the G-protein. Activity on G(z)-alpha and G(i)-alpha-1 is inhibited by palmitoylation of the G-protein.|||Phosphorylated by cyclic GMP-dependent protein kinase. http://togogenome.org/gene/10090:Fgd5 ^@ http://purl.uniprot.org/uniprot/E9QKY4|||http://purl.uniprot.org/uniprot/Q80UZ0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Mediates VEGF-induced CDC42 activation. May regulate proangiogenic action of VEGF in vascular endothelial cells, including network formation, directional movement and proliferation. May play a role in regulating the actin cytoskeleton and cell shape (By similarity).|||Detected at 10 dpc in the intersomitic vessels, dorsal aorta and brain vasculature. In retina, strongly expressed in the developing retinal vasculature at postnatal day 4 and down-regulated in preformed vessels at postnatal day 8. Predominantly detected in capillaries and veins, and particularly at the advancing vascular fronts, as compared to arteries.|||Early endosome|||Endoplasmic reticulum|||Expressed in highly vascularized tissues, such as lung, kidney and ovary.|||Golgi apparatus|||cytoskeleton|||ruffle membrane http://togogenome.org/gene/10090:Serpina1b ^@ http://purl.uniprot.org/uniprot/P22599 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the serpin family.|||Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin.|||Murine alpha-1-antitrypsin is represented by a cluster of up to 6 individual Serpina1-related genes. The precise complement of Serpina1-related genes present varies according to the strain of the animal.|||Secreted|||The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity). Variability within the reactive center loop (RCL) sequences of Serpina1-related genes may determine target protease specificity. http://togogenome.org/gene/10090:Foxp1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1H9|||http://purl.uniprot.org/uniprot/A0A0R4J282|||http://purl.uniprot.org/uniprot/D3Z6Q3|||http://purl.uniprot.org/uniprot/E2S038|||http://purl.uniprot.org/uniprot/H3BJ24|||http://purl.uniprot.org/uniprot/H3BLF2|||http://purl.uniprot.org/uniprot/P58462 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in developing lung, neural, intestinal and cardiovascular tissues. Expressed in both the airway epithelium of the forming lung as well as in the surrounding mesenchyme. By 16.5 dpc, expressed throughout the conducting airway epithelium, with highest expression in the distal alveolar regions. Also expressed in the endotheial cells of the pulmonary vasculature. During intestinal development, expressed in the mucosal layer but absent from the epithelium at 12.5 dpc. By 16.5 dpc, expressed in both the inner circular and outer longitudinal muscular layers of the intestine as well as in the epithelium of the intestine and developing stomach (PubMed:14516685). Expressed in 12.5 dpc midbrain dopaminergic neurons (PubMed:20175877).|||Forms homodimers and heterodimers with FOXP2 and FOXP4. Dimerization is required for DNA-binding. Self-associates (By similarity). Interacts with CTBP1 (PubMed:14701752). Interacts with NCOR2 and AR. Interacts with FOXP2 (By similarity). Interacts with TBR1 (By similarity). Interacts with AURKA; this interaction facilitates the phosphorylation of FOXP1, which suppresses the expression of FBXL7 (By similarity). Interacts with ZMYM2 (By similarity).|||Involved in transcriptional regulation in embryonic stem cells (ESCs). Stimulates expression of transcription factors that are required for pluripotency and decreases expression of differentiation-associated genes. Has distinct DNA-binding specifities as compared to the canonical form and preferentially binds DNA with the sequence 5'-CGATACAA-3' (or closely related sequences) (By similarity). Promotes ESC self-renewal and pluripotency (PubMed:21924763).|||Isoform 5 is specifically expressed in embryonic stem cells (PubMed:21924763). Highest expression in the lung, brain, and spleen. Lower expression in heart, skeletal muscle, kidney, small intestine (isoform 3 not present) and liver.|||Nucleus|||Produced by alternative initiation at Met-251 of isoform 1.|||Produced by alternative splicing.|||The leucine-zipper is required for dimerization and transcriptional repression.|||Transcriptional repressor. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential (PubMed:11358962, PubMed:14701752). Plays an important role in the specification and differentiation of lung epithelium. Acts cooperatively with FOXP4 to regulate lung secretory epithelial cell fate and regeneration by restricting the goblet cell lineage program; the function may involve regulation of AGR2 (PubMed:11358962, PubMed:22675208). Essential transcriptional regulator of B-cell development (PubMed:16819554). Involved in regulation of cardiac muscle cell proliferation (PubMed:20713518). Involved in the columnar organization of spinal motor neurons. Promotes the formation of the lateral motor neuron column (LMC) and the preganglionic motor column (PGC) and is required for respective appropriate motor axon projections. The segment-appropriate generation of spinal cord motor columns requires cooperation with other Hox proteins (PubMed:18667151, PubMed:18662545). Can regulate PITX3 promoter activity; may promote midbrain identity in embryonic stem cell-derived dopamine neurons by regulating PITX3 (PubMed:20175877). Negatively regulates the differentiation of T follicular helper cells T(FH)s (PubMed:24859450). Involved in maintenance of hair follicle stem cell quiescence; the function probably involves regulation of FGF18 (PubMed:23946441). Represses transcription of various pro-apoptotic genes and cooperates with NF-kappa B-signaling in promoting B-cell expansion by inhibition of caspase-dependent apoptosis. Binds to CSF1R promoter elements and is involved in regulation of monocyte differentiation and macrophage functions; repression of CSF1R in monocytes seems to involve NCOR2 as corepressor. Involved in endothelial cell proliferation, tube formation and migration indicative for a role in angiogenesis; the role in neovascularization seems to implicate suppression of SEMA5B. Can negatively regulate androgen receptor signaling (By similarity). Acts as a transcriptional activator of the FBXL7 promoter; this activity is regulated by AURKA (By similarity). http://togogenome.org/gene/10090:Cdv3 ^@ http://purl.uniprot.org/uniprot/A0A087WNP6|||http://purl.uniprot.org/uniprot/F8WGL9|||http://purl.uniprot.org/uniprot/Q4VAA2 ^@ PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CDV3 family.|||Cytoplasm|||Isoform 1 and isoform 2 are phosphorylated on tyrosines by ABL1 in B-cells.|||Ubiquitously expressed (at protein level). Up-regulated in ventricles of juvenile visceral steatosis mice. http://togogenome.org/gene/10090:Cutc ^@ http://purl.uniprot.org/uniprot/F8WHX2|||http://purl.uniprot.org/uniprot/Q9D725|||http://purl.uniprot.org/uniprot/Q9D8X1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CutC family.|||Cytoplasm|||Homotetramer.|||May play a role in copper homeostasis. Can bind one Cu(1+) per subunit (By similarity).|||Nucleus http://togogenome.org/gene/10090:Gucy2d ^@ http://purl.uniprot.org/uniprot/A0A0U1RPR8 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by Ca(2+).|||Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.|||Deficient mice lack olfactory response to uroguanylin and guanylin.|||Found in a subset of olfactory neurons in the main olfactory epithelium.|||Functions as an olfactory receptor activated by urine odorants, uroguanylin and guanylin and as well by the volatile semiochemicals carbon disulfide (CS2) and carbon dioxide (CO2) (PubMed:17724338, PubMed:17702944, PubMed:20637621). Has guanylate cyclase activity upon binding of the ligand (By similarity). Activation of GUCY2D neurons leads to the cGMP-dependent activation of the CNGA3 channels, membrane depolarization and an increase in action potential frequency (PubMed:17724338, PubMed:20637621). Signaling pathways activated by GUCY2D may trigger social behaviors such as acquisition of food preference (PubMed:20637621).|||Interacts (via the catalytic domain) with NCALD.|||The gene names for receptor guanylyl cyclases are inconsistent between mouse and human. The ortholog of the mouse Gucy2d gene is a pseudogene in humans. The mouse Gucy2d is not an ortholog of the human GUCY2D gene, the latter of which encodes a retinal receptor guanylyl cyclase involved in phototransduction.|||The protein kinase domain is predicted to be catalytically inactive.|||cilium membrane http://togogenome.org/gene/10090:Map3k7 ^@ http://purl.uniprot.org/uniprot/Q543B5|||http://purl.uniprot.org/uniprot/Q62073|||http://purl.uniprot.org/uniprot/Q923A8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 'Lys-48'-linked polyubiquitination at Lys-72 is induced by TNFalpha, and leads to proteasomal degradation (PubMed:16157589). Undergoes 'Lys-48'-linked polyubiquitination catalyzed by ITCH (PubMed:25632008). 'Lys-63'-linked polyubiquitination at Lys-158 by TRIM8 does not lead to proteasomal degradation but contributes to autophosphorylation and activation. Deubiquitinated by CYLD, a protease that selectively cleaves 'Lys-63'-linked ubiquitin chains (PubMed:17548520, PubMed:29291351).|||Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation (PubMed:20060931). Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation (PubMed:29291351). Association with TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 promotes activation through autophosphorylation, whereas PPM1B/PP2CB, PP2A and PPP6C dephosphorylation leads to inactivation (By similarity). Ceramides are also able to activate MAP3K7/TAK1 (By similarity).|||Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation. Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation.|||Association with TAB1/MAP3K7IP1 promotes autophosphorylation and subsequent activation. Association with TAB2/MAP3K7IP2, itself associated with free unanchored Lys-63 polyubiquitin chain, promotes autophosphorylation and subsequent activation of MAP3K7. Dephosphorylation at Thr-187 by PP2A and PPP6C leads to inactivation (By similarity).|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.|||Can form homodimer (By similarity). Binds both upstream activators and downstream substrates in multimolecular complexes (By similarity). Interacts with TAB1/MAP3K7IP1, TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3 (By similarity). Identified in the TRIKA2 complex composed of MAP3K7/TAK1, TAB1/MAP3K7IP1 and TAB2/MAP3K7IP2 (By similarity). Interacts with PPM1L and PPM1B/PP2CB (PubMed:12556533). Interaction with PP2A and PPP6C leads to its repressed activity (By similarity). Interacts with TRAF6 and TAB1/MAP3K7IP1; during IL-1 signaling (By similarity). Interacts with TAOK1 and TAOK2; interaction with TAOK2 interferes with MAP3K7 interaction with IKKA, thus preventing NF-kappa-B activation (By similarity). Interacts with DYNC2I2 (via WD domains) (By similarity). Interacts with CYLD and RBCK1 (PubMed:17548520). Interacts with TGFBR1; induces MAP3K7/TAK1 activation by TRAF6 (By similarity). Interacts with MAPK8IP1 and SMAD6 (PubMed:10748100, PubMed:17709393). Interacts with isoform 1 of VRK2 (PubMed:17709393). Interacts with DAB2; the interaction is induced by TGF-beta stimulation and may mediate TGF-beta stimulated JNK activation (By similarity). Interacts with TRIM5 (By similarity). Part of a complex containing ITCH, NDFIP1 and MAP3K7 (PubMed:25632008). Interacts with PLEKHM1 (via N- and C-terminus) (PubMed:27777970). Interacts with TRIM8 (By similarity). Found in a complex with SH3RF1, RAC2, MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103). Interacts with SASH1 (By similarity). Interacts with RIPK1 (PubMed:31519887).|||Cell membrane|||Cytoplasm|||Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10748100, PubMed:16157589, PubMed:21183079, PubMed:29291351). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10748100, PubMed:16157589, PubMed:21183079, PubMed:29291351). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:8533096, PubMed:10748100, PubMed:16157589, PubMed:21183079, PubMed:29291351). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (By similarity). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (By similarity). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:17965022). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (By similarity). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (By similarity). Promotes TRIM5 capsid-specific restriction activity (By similarity). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (PubMed:28842570). http://togogenome.org/gene/10090:Atp6v0c ^@ http://purl.uniprot.org/uniprot/A3KML5|||http://purl.uniprot.org/uniprot/P63082 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase proteolipid subunit family.|||Membrane|||Proton-conducting pore forming of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.|||Proton-conducting pore forming subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).|||Ubiquitinated by RNF182, leading to its degradation via the ubiquitin-proteasome pathway.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with the V0 complex V-ATPase subunit a4 ATP6V0A4 (PubMed:11495928). Interacts with LASS2 (By similarity). Interacts with RNF182; this interaction leads to ubiquitination and degradation via the proteasome pathway (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits.|||Vacuole membrane|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Nupr1l ^@ http://purl.uniprot.org/uniprot/Q497P3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a transcriptional repressor by inhibiting gene expression at the NUPR1 promoter in a p53/TP53-dependent manner in cancer cells. Involved in the G1 cell cycle arrest, and in a decrease in cell viability and cell proliferation of pancreatic cancer cells. Plays a role as a negative regulator of the protumoral factor NUPR1.|||Belongs to the NUPR family.|||Nucleus http://togogenome.org/gene/10090:Gimap3 ^@ http://purl.uniprot.org/uniprot/Q99MI6 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.|||By BCR-ABL oncogene.|||During thymocyte development, may support the positive selection of CD4 and CD8 T cells (PubMed:16509771). May play a role in mitochondrial DNA segregation in hematopoietic tissues (PubMed:25808953). Binds GTP (PubMed:11238997).|||Endoplasmic reticulum membrane|||Expressed in thymus (in thymocytes), spleen (in splenocytes), lymph node and, at lower levels, in lung (PubMed:16509771, PubMed:25808953). Highly expressed in T lymphocytes (PubMed:16509771).|||Interacts with BAD, BAK1, BAX, BCL2, BCL2L1/Bcl-xL and BCL2L11/BimEL (PubMed:16509771). The interaction with BAX is increased, when cells initiate apoptosis upon IL2 withdrawal (PubMed:16509771).|||Up-regulated upon the maturation of CD4/CD8 double-positive to CD4 single-positive thymocytes. http://togogenome.org/gene/10090:Asb9 ^@ http://purl.uniprot.org/uniprot/Q91ZT8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Mitochondrion|||Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes at least two forms of creatine kinase, CKB and CKMT1A (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Hspa2 ^@ http://purl.uniprot.org/uniprot/P17156 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the heat shock protein 70 family.|||Expressed in male germ cells (at protein level) (PubMed:24557841, PubMed:23055941, PubMed:3405224).|||Interacts with FKBP6 (By similarity). Interacts with ZNF541 (PubMed:18849567). Component of the CatSper complex (PubMed:21224844). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941). Interacts with SHCBP1L; this interaction may promote the recruitment of HSPA2 to the spindle (PubMed:24557841). Interacts with MOV10L1 (PubMed:20547853).|||Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (By similarity). Plays a role in spermatogenesis (PubMed:24557841). In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (PubMed:24557841).|||Specifically expressed in prophage stage of meiosis (PubMed:3405224).|||The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.|||spindle http://togogenome.org/gene/10090:Cntnap5b ^@ http://purl.uniprot.org/uniprot/Q0V8T8 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neurexin family.|||Expressed from 6 dpc in brain.|||Expressed in brain.|||May play a role in the correct development and proper functioning of the peripheral and central nervous system and be involved in cell adhesion and intercellular communication.|||Membrane http://togogenome.org/gene/10090:P2ry1 ^@ http://purl.uniprot.org/uniprot/P49650|||http://purl.uniprot.org/uniprot/Q544J5|||http://purl.uniprot.org/uniprot/Q8BMJ5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Platelets from mutant mice are defective in ADP-mediated platelet aggregation, leading to prolonged bleeding time. Otherwise, mice have no visible phenotype and do not display spontaneous bleeding.|||Receptor for extracellular adenine nucleotides such as ADP. In platelets, binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and ultimately platelet aggregation. http://togogenome.org/gene/10090:Prl3d1 ^@ http://purl.uniprot.org/uniprot/A0A286YC78|||http://purl.uniprot.org/uniprot/Q8BNL4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Secreted http://togogenome.org/gene/10090:Kyat1 ^@ http://purl.uniprot.org/uniprot/Q8BTY1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA), an intermediate in the tryptophan catabolic pathway which is also a broad spectrum antagonist of the three ionotropic excitatory amino acid receptors among others. Metabolizes the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites. Catalyzes the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond.|||Homodimer.|||cytosol http://togogenome.org/gene/10090:Prxl2b ^@ http://purl.uniprot.org/uniprot/Q9DB60 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peroxiredoxin-like PRXL2 family. Prostamide/prostaglandin F synthase subfamily.|||Catalyzes the reduction of prostaglandin-ethanolamide H(2) (prostamide H(2)) to prostamide F(2alpha) with NADPH as proton donor. Also able to reduce prostaglandin H(2) to prostaglandin F(2alpha).|||Mainly present in brain and spinal cord. In spinal cord, present in the superficial layer of the dorsal horn, in motor neurons of the ventral horn and in glia of the white matter of the spinal cord. In brain, expressed preferentially in the white matter bundles of the entire CNS of adult with less marked expression in neuronal cell bodies. Colocalizes with MBP in myelin sheaths but not in axons. Localizes to myelin sheaths (at protein level).|||cytosol http://togogenome.org/gene/10090:1110038F14Rik ^@ http://purl.uniprot.org/uniprot/Q3U6N9 ^@ Similarity ^@ Belongs to the UPF0488 family. http://togogenome.org/gene/10090:Hbegf ^@ http://purl.uniprot.org/uniprot/Q06186|||http://purl.uniprot.org/uniprot/Q5FW64 ^@ Caution|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor.|||Interacts with FBLN1 (By similarity). Interacts with EGFR and ERBB4.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Most abundant in kidney, skeletal muscle, lung, spleen, brain and heart.|||O-glycosylated.|||extracellular space http://togogenome.org/gene/10090:Or51b17 ^@ http://purl.uniprot.org/uniprot/F8VPZ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ap3m2 ^@ http://purl.uniprot.org/uniprot/Q8R2R9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (By similarity). AP-3 associates with the BLOC-1 complex.|||Belongs to the adaptor complexes medium subunit family.|||Component of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. Ap47 is a subunit of the plasma membrane adaptor (By similarity). In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.|||Cytoplasmic vesicle membrane|||Golgi apparatus http://togogenome.org/gene/10090:Pmm2 ^@ http://purl.uniprot.org/uniprot/Q545N8|||http://purl.uniprot.org/uniprot/Q9Z2M7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic PMM family.|||Cytoplasm|||Homodimer.|||Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. http://togogenome.org/gene/10090:Or4k38 ^@ http://purl.uniprot.org/uniprot/Q7TQY5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Osbpl2 ^@ http://purl.uniprot.org/uniprot/Q8BX94 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OSBP family.|||Cell membrane|||Detected in cochlea, in inner and outer hair cells in the organ of Corti (at protein level).|||Intracellular transport protein that binds sterols and phospholipids and mediates lipid transport between intracellular compartments. Increases plasma membrane cholesterol levels and decreases phosphatidylinositol-4,5-bisphosphate levels in the cell membrane. Binds phosphoinositides, such as phosphatidylinositol-4,5-bisphosphate. Exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Binds cholesterol, dehydroergosterol, 22(R)-hydroxycholesterol and 25-hydroxycholesterol (in vitro).|||Lipid droplet|||Monomer. Homotetramer; phosphatidylinositol-4,5-bisphosphate binding promotes formation of stable tetramers. Interacts with DIAPH1.|||cytosol http://togogenome.org/gene/10090:Ap2m1 ^@ http://purl.uniprot.org/uniprot/P84091|||http://purl.uniprot.org/uniprot/Q3TWV4|||http://purl.uniprot.org/uniprot/Q5FWI9|||http://purl.uniprot.org/uniprot/Q6A0C9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1) (By similarity). Interacts with ATP6V1H and MEGF10 (By similarity). Interacts with EGFR and TTGN1 (By similarity). Interacts with F2R (By similarity). Interacts with PIP5K1C isoform 1; tyrosine phosphorylation of PIP5K1C weakens the interaction. Does not interact with PIP5K1C isoform 3 (PubMed:16707488). Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319 (By similarity). Interacts with DVL2 (via DEP domain) (By similarity). Interacts with KCNQ1; mediates estrogen-induced internalization via clathrin-coated vesicles (By similarity). Interacts with P2RX4 (via internalization motif) (By similarity). Together with AP2A1 or AP2A2 and AP2B1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Probably interacts with ACE2 (via endocytic sorting signal motif); the interaction is inhibited by ACE2 phosphorylation (By similarity). Interacts with RALBP1; the interaction is direct (PubMed:10910768). Interacts with TMEM106B (via N-terminus) (By similarity).|||Belongs to the adaptor complexes medium subunit family.|||Cell membrane|||Component of the adaptor protein complex 2 (AP-2) (PubMed:14745134, PubMed:15473838). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways (PubMed:14745134, PubMed:15473838). Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation (PubMed:14745134, PubMed:15473838). AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome (PubMed:14745134, PubMed:15473838). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components (PubMed:14745134, PubMed:15473838). Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation (By similarity). AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis (By similarity). AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface (By similarity). AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules (By similarity). AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (By similarity). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs (By similarity). The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at Thr-156 in membrane-associated AP-2 (By similarity). The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity).|||Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules.|||Embryonic lethal before day 3.5 postcoitus (E3.5).|||Expressed in the brain (at protein level) (PubMed:23676497). Detected in spleen.|||Phosphorylation at Thr-156 increases the affinity of the AP-2 complex for cargo membrane proteins during the initial stages of endocytosis.|||coated pit http://togogenome.org/gene/10090:Vav3 ^@ http://purl.uniprot.org/uniprot/Q9R0C8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subunit|||Tissue Specificity ^@ Abundantly expressed in osteoclasts and mature osteoblasts. Also expressed in bone marrow macrophages (at protein level):.|||Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1. Binds physically to the nucleotide-free states of those GTPases (By similarity). Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. May be important for integrin-mediated signaling, at least in some cell types. In osteoclasts, along with SYK tyrosine kinase, required for signaling through integrin alpha-v/beta-1 (ITAGV-ITGB1), a crucial event for osteoclast proper cytoskeleton organization and function. This signaling pathway involves RAC1, but not RHO, activation. Necessary for proper wound healing. In the course of wound healing, required for the phagocytotic cup formation preceding macrophage phagocytosis of apoptotic neutrophils. Responsible for integrin beta-2-mediated macrophage adhesion and, to a lesser extent, contributes to beta-3-mediated adhesion. Does not affect integrin beta-1-mediated adhesion.|||Interacts with the PH domain of APS. Interacts with ROS1; constitutive interaction that mediates VAV3 phosphorylation (By similarity). Interacts (via SH2 domains) with the phosphorylated form of EPHA2.|||Mutant mice exhibit increased bone density, due to diminished bone resorption, including following parathyroid hormone treatment. This phenotype is due to defective terminal osteoclast differentiation. They also show a delayed wound repair program, characterized by a deficit in macrophage emigration to the wound, a reduced myofibroblast-dependent wound contraction and a diminished neovascularization in the restoration tissue.|||Phosphorylated. Phosphorylation can be mediated by ROS1 (By similarity). In osteoclasts, undergoes tyrosine phosphorylation in response to CSF1.|||Produced by alternative promoter usage.|||Produced by alternative splicing. http://togogenome.org/gene/10090:Fam221b ^@ http://purl.uniprot.org/uniprot/Q8C627 ^@ Similarity ^@ Belongs to the FAM221 family. http://togogenome.org/gene/10090:Or4c52 ^@ http://purl.uniprot.org/uniprot/Q8VG63 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ugt2b5 ^@ http://purl.uniprot.org/uniprot/Q3UWB9|||http://purl.uniprot.org/uniprot/Q8K169 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane http://togogenome.org/gene/10090:Vmn2r15 ^@ http://purl.uniprot.org/uniprot/A0A3B2WCV8|||http://purl.uniprot.org/uniprot/L7N2A0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Timm8b ^@ http://purl.uniprot.org/uniprot/P62077 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small Tim family.|||Heterohexamer; possibly composed of 3 copies of TIMM8B and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22 (By similarity).|||Mitochondrion inner membrane|||Probable mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity).|||The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8B from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity). http://togogenome.org/gene/10090:Ipo8 ^@ http://purl.uniprot.org/uniprot/Q7TMY7 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Abundantly expressed in secretory and mature ameloblasts and weakly expressed in pre-ameloblasts of the lower incisor and molar at birth (at protein level).|||Belongs to the importin beta family.|||Cytoplasm|||Forms a heterodimer with KPNB1. Interacts with SRP19. Interacts with RPL23A. Binds directly to nuclear pore complexes. Interacts with LRPPRC; the interaction occurs when LRPPRC is in its RNA-free form and promotes import of LRPPRC to the nucleus to allow for EIF4E-mediated export of mRNAS from the nucleus to the cytoplasm.|||Involved in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, may serve as receptor for nuclear localization signals (NLS) and promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro mediates the nuclear import of the signal recognition particle protein SRP19. May also be involved in cytoplasm-to-nucleus shuttling of a broad spectrum of other cargos, including Argonaute-microRNAs complexes, the JUN protein, RELA/NF-kappa-B p65 subunit, the translation initiation factor EIF4E and a set of receptor-activated mothers against decapentaplegic homolog (SMAD) transcription factors that play a critical role downstream of the large family of transforming growth factor beta and bone morphogenetic protein (BMP) cytokines.|||Knockout animals present with reduced grip strength and diminished vertical activity. Progressive dilatation can be observed in the aortic root at the level of the sinuses of Valsalva and distal ascending aorta, and aneurysms of the distal ascending aorta are becoming visible at the age of 8-12 weeks. Generally, males are more severely affected, exhibiting larger aortas and experiencing dissection and/or rupture more frequently than females.|||Nucleus|||The regions from 407 to 653 were deduced from the genomic sequence and ESTs by similarity to the human sequence. http://togogenome.org/gene/10090:Sfpq ^@ http://purl.uniprot.org/uniprot/Q8VIJ6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as transcriptional activator (By similarity). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF-I-stimulated transcriptional activity (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (PubMed:21680841, PubMed:22966205). Required for the assembly of nuclear speckles (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (By similarity).|||Heterodimer with NONO. Monomer and component of the SFPQ-NONO complex, which is probably a heterotetramer of two 52 kDa (NONO) and two 100 kDa (SFPQ) subunits. The coiled coil domain mediates interaction with NONO, and can also mediate formation of long, linear homooligomers (in vitro). SFPQ is a component of spliceosome and U5.4/6 snRNP complexes. Interacts with SNRPA/U1A. Component of a snRNP-free complex with SNRPA/U1A. Part of complex consisting of SFPQ, NONO and MATR3. Interacts with polypyrimidine tract-binding protein 1/PTB. Part of a complex consisting of SFPQ, NONO and NR5A1. Interacts with RXRA, probably THRA, and SIN3A. Interacts with TOP1. Part of a complex consisting of SFPQ, NONO and TOP1. Interacts with SNRNP70 in apoptotic cells. Interacts with PSPC1 (PubMed:15140795). Interacts with RNF43 (By similarity). Interacts with PITX3 and NR4A2/NURR1 (PubMed:19144721). Interacts with PTK6. Interacts with THRAP3; the interaction is dependent on SFPQ phosphorylation at 'Thr-687' and inhibits binding of SFPQ to a ESS1 exonic splicing silencer element-containing RNA (By similarity). The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A (PubMed:21680841). Interacts with PER1 and PER2 (PubMed:22966205). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA (By similarity). Interacts with PQBP1. Component of a multiprotein complex with NONO and WASL (By similarity). Interacts with ERCC6 (By similarity).|||Nucleus matrix|||Nucleus speckle|||Phosphorylated on multiple serine and threonine residues during apoptosis (By similarity). Phosphorylation of C-terminal tyrosines promotes its cytoplasmic localization, impaired its binding to polypyrimidine RNA and led to cell cycle arrest (By similarity). In resting T-cells is phosphorylated at Thr-679 by GSK3B which is proposed to promote association with THRAP and to prevent binding to PTPRC/CD45 pre-mRNA; T-cell activation leads to reduced phosphorylation at Thr-679.|||The coiled coil domain mediates interaction with NONO, and can also mediate formation of long, linear homooligomers (in vitro). The coiled coil domain is required for optimal DNA binding, and optimal transcription activation. http://togogenome.org/gene/10090:4930447C04Rik ^@ http://purl.uniprot.org/uniprot/Q9CTN5 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Interacts with SYCE1 (PubMed:27796301). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (PubMed:31437213).|||Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination (PubMed:27796301, PubMed:33508233). Required for the appropriate processing of intermediate recombination nodules before crossover formation (PubMed:27796301).|||Mice develop normally but males and females are sterile due to defects in chromosome synapsis at meiotic prophase I (PubMed:27796301). Spermatogenesis proceeds normally up to prophase I until a massive apoptosis of spermatocytes takes place at stage IV (PubMed:27796301). Ovaries of female mice at 4 months of age display a lack of oocytes (PubMed:27796301).|||Most abundantly expressed in testis (PubMed:27796301). Also expressed in retina and skeletal muscle (PubMed:15703187). http://togogenome.org/gene/10090:Omp ^@ http://purl.uniprot.org/uniprot/Q64288 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the olfactory marker protein family.|||Cytoplasm|||Interacts with BEX1 and BEX2.|||May act as a modulator of the olfactory signal-transduction cascade.|||Uniquely associated with mature olfactory receptor neurons. http://togogenome.org/gene/10090:Rwdd3 ^@ http://purl.uniprot.org/uniprot/E9Q1R6|||http://purl.uniprot.org/uniprot/Q3UYX7 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Crygf ^@ http://purl.uniprot.org/uniprot/Q9CXV3 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity ^@ Belongs to the beta/gamma-crystallin family.|||Crystallins are the dominant structural components of the vertebrate eye lens.|||Has a two-domain beta-structure, folded into four very similar Greek key motifs.|||In the embryo, expressed by day 12 of gestation. Maximum levels are found at day 30-40 followed by a rapid decline.|||There are six different gamma crystallins identified in mouse lens. http://togogenome.org/gene/10090:Ssxb2 ^@ http://purl.uniprot.org/uniprot/Q80ZT4|||http://purl.uniprot.org/uniprot/Q8C5Z3 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Fbp1 ^@ http://purl.uniprot.org/uniprot/Q9QXD6 ^@ Activity Regulation|||Cofactor|||Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the FBPase class 1 family.|||Binds 3 Mg(2+) ions per subunit.|||Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain.|||Detected in pancreatic beta-cell lines MIN6 and beta-TC and in liver (at protein level). Preferentially expressed in liver, with lower levels detected in pancreatic islets and intestine, and very low levels in blood, muscle, brain and spleen.|||Homotetramer.|||Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects (By similarity).|||Up-regulated in pancreas by obesity and dietary fat intake and in diabetic animals. http://togogenome.org/gene/10090:Alg14 ^@ http://purl.uniprot.org/uniprot/Q9D081 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ALG14 family.|||Endoplasmic reticulum membrane|||Heterodimer with ALG13 to form a functional enzyme.|||Involved in protein N-glycosylation. Essential for the second step of the dolichol-linked oligosaccharide pathway. Anchors the catalytic subunit ALG13 to the ER (By similarity).|||Nucleus membrane http://togogenome.org/gene/10090:Rin1 ^@ http://purl.uniprot.org/uniprot/Q921Q7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RIN (Ras interaction/interference) family.|||Cytoplasm|||Highly expressed in brain. Weakly or no expressed in other tissues, except in testis, where it is expressed at intermediate level. In brain, it is mainly expressed in postnatal forebrain neurons in which it is localized in dendrites and colocalizes with Ras.|||Interacts with the GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). This interaction prevents the association between RAF1 and Ras. Interacts with 14-3-3 proteins YWHAB, YWHAE and YWHAZ when phosphorylated on Ser-340. Interacts with the SH3 domain of ABL1 and ABL2. Interacts with RAB5A. The interaction with Ras is probably regulated and antagonized by the interaction with 14-3-3 proteins. The interaction with 14-3-3 proteins is regulated by phosphorylation on Ser-340 (By similarity).|||Membrane|||Phosphorylated on tyrosine residues by ABL1 and ABL2. Phosphorylation at Ser-340 by PRKD1 induces interaction with 14-3-3 proteins (By similarity).|||Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. Can affect Ras signaling at different levels. First, by competing with RAF1 protein for binding to activated Ras. Second, by enhancing signaling from ABL1 and ABL2, which regulate cytoskeletal remodeling. Third, by activating RAB5A, possibly by functioning as a guanine nucleotide exchange factor (GEF) for RAB5A, by exchanging bound GDP for free GTP, and facilitating Ras-activated receptor endocytosis (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Slc6a8 ^@ http://purl.uniprot.org/uniprot/A2ALM6|||http://purl.uniprot.org/uniprot/Q8VBW1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A8 subfamily.|||Brain. Highly expressed in brain capillaries branching in all cortical layers and moderately expressed in neuronal perikarya (at protein level).|||Cell membrane|||Creatine:sodium symporter which mediates the uptake of creatine (PubMed:12439290). Plays an important role in supplying creatine to the brain via the blood-brain barrier (PubMed:12439290).|||Glycosylated.|||Membrane http://togogenome.org/gene/10090:Ifna15 ^@ http://purl.uniprot.org/uniprot/Q61718 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Camsap1 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQE5|||http://purl.uniprot.org/uniprot/A2AHC3 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CAMSAP1 family.|||Expressed in the central nervous system.|||Highly and ubiquitously expressed in the brain and throughout the first pharyngeal arch, and neural tube at 10.5 dpc. At 14.5 dpc, expression in the brain becomes slightly more localized to the ganglionic eminences and cortex, and present in the caudal neural tube. At late stages of neurogenesis (18.5 dpc), it is most highly expressed in the cortex, particularly in upper layers of differentiated neurons and the ventricular zone. Postnatally, expression is particularly evident in upper cortical layers and in the hippocampus.|||Interacts with spectrin via SPTBN1; the interaction is direct. Interacts with calmodulin; calcium-dependent it prevents interaction with spectrin.|||Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization. Specifically recognizes growing microtubule minus-ends and stabilizes microtubules. Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization. In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation. Through interaction with spectrin may regulate neurite outgrowth.|||The CKK domain binds microtubules.|||cytoskeleton http://togogenome.org/gene/10090:Ddx28 ^@ http://purl.uniprot.org/uniprot/Q9CWT6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family.|||Mitochondrion|||Mitochondrion matrix|||Monomer. Found in a complex with GRSF1, DHX30, FASTKD2 and FASTKD5. Associates with the 16S mitochondrial rRNA (16S mt-rRNA) and with the mitochondrial ribosome large subunit (39S).|||Nucleus|||Plays an essential role in facilitating the proper assembly of the mitochondrial large ribosomal subunit and its helicase activity is essential for this function. May be involved in RNA processing or transport. Has RNA and Mg(2+)-dependent ATPase activity (By similarity).|||mitochondrion nucleoid http://togogenome.org/gene/10090:Ccr6 ^@ http://purl.uniprot.org/uniprot/O54689|||http://purl.uniprot.org/uniprot/Q542B6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Cell surface|||Membrane|||Receptor for the C-C type chemokine CCL20. Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25122636). Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity (By similarity). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma (PubMed:21376174). CCR6 is essential for the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation (PubMed:19050256). Required for the normal migration of Th17 cells in Peyers patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine (PubMed:19129757). Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors (PubMed:24638065). Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches (PubMed:27174992). Essential for appropriate anatomical distribution of memory B-cells in the spleen and for the secondary recall response of memory B-cells (PubMed:25505290). Positively regulates sperm motility and chemotaxis via its binding to CCL20 (PubMed:23765988).|||Sperm. Mainly localized in the principal piece and neck region of the tail but is also found in the acrosomal region in a small percentage of sperm cells. Expressed in natural regulatory T cells (nTregs) and a subset of early thymocyte progenitor double-negative 1 (DN1) cells. Expressed in memory B cells. Expressed by IL17 producing helper T-cells (Th17), type 1 effector cells (Th1), type 2 effector cells (Th2) and regulatory T-cells (Treg) (at protein level). Expressed by Th17 cells in spleen, Peyers patches, and lamina propria of small and large intestine. Highly expressed in testis, lung, colon, and dendritic cells.|||Up-regulated on pre-germinal center B-cells in a CD40-dependent manner. Up-regulated and down-regulated in Th17 cells by TGFB1 and IL2 respectively. http://togogenome.org/gene/10090:Sftpc ^@ http://purl.uniprot.org/uniprot/Q6P8P8 ^@ Function|||Subcellular Location Annotation ^@ Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces.|||surface film http://togogenome.org/gene/10090:Proc ^@ http://purl.uniprot.org/uniprot/P33587 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Calcium also binds, with stronger affinity to another site, beyond the GLA domain. This GLA-independent binding site is necessary for the recognition of the thrombin-thrombomodulin complex.|||Endoplasmic reticulum|||Golgi apparatus|||Plasma; synthesized in the liver.|||Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids. Exerts a protective effect on the endothelial cell barrier function.|||Secreted|||Synthesized as a single chain precursor, which is cleaved into a light chain and a heavy chain held together by a disulfide bond. The enzyme is then activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain; this reaction, which occurs at the surface of endothelial cells, is strongly promoted by thrombomodulin.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.|||The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium. http://togogenome.org/gene/10090:Mmp15 ^@ http://purl.uniprot.org/uniprot/O54732 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Endopeptidase that degrades various components of the extracellular matrix. May activate progelatinase A.|||Membrane|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase. http://togogenome.org/gene/10090:Tfpi2 ^@ http://purl.uniprot.org/uniprot/O35536|||http://purl.uniprot.org/uniprot/Q3V1S9 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Finds in a complex with ABCB1, TFPI2 and PPP2R3C; leading to the dephosphorylation of ABCB1.|||Highly expressed in placenta. Also expressed in liver and kidney.|||May play a role in the regulation of plasmin-mediated matrix remodeling. Inhibits trypsin, plasmin, factor VIIa/tissue factor and weakly factor Xa. Has no effect on thrombin (By similarity).|||Secreted|||This inhibitor contains three inhibitory domains. http://togogenome.org/gene/10090:Dcaf10 ^@ http://purl.uniprot.org/uniprot/A2AKB9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the WD repeat DCAF10 family.|||Interacts with DDB1.|||May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. http://togogenome.org/gene/10090:Sh3bp5l ^@ http://purl.uniprot.org/uniprot/Q3TK15|||http://purl.uniprot.org/uniprot/Q99LH9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SH3BP5 family.|||Cytoplasm|||Functions as guanine nucleotide exchange factor (GEF) for RAB11A.|||Interacts with GDP-bound and nucleotide-free forms of RAB11A.|||The N-terminal half of the protein mediates interaction with RAB11A and functions as guanine nucleotide exchange factor. Four long alpha-helices (interrupted by a central kink) assemble into coiled coils, giving rise to a 'V' shape. http://togogenome.org/gene/10090:Gabrg1 ^@ http://purl.uniprot.org/uniprot/Q9R0Y8 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG1 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.|||May be palmitoylated.|||Postsynaptic cell membrane|||This subunit carries the benzodiazepine binding site. http://togogenome.org/gene/10090:Chadl ^@ http://purl.uniprot.org/uniprot/E9Q7T7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with collagen and binds to collagen fibrils.|||Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily.|||Expressed in cartilage, including articular knee cartilage, where it localizes to the extracellular space in the area immediately surrounding the chondrocytes, not detected in any other tissues (at protein level).|||Not detected before 13.5 dpc. From 13.5 dpc on, prominently expressed only in mesenchymal condensations and in cartilaginous tissues. In the ATDC5 cell line model, up-regulated during chondrocyte differentiation, absent in precondrogenic, non-differentiating stage (at protein level).|||Potential negative modulator of chondrocyte differentiation. Inhibits collagen fibrillogenesis in vitro. May influence chondrocyte's differentiation by acting on its cellular collagenous microenvironment.|||extracellular matrix http://togogenome.org/gene/10090:Psme4 ^@ http://purl.uniprot.org/uniprot/Q5SSW2 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks.|||Belongs to the BLM10 family.|||Broadly expressed. Present in heart (at protein level).|||Homodimer. Interacts with the 20S and 26S proteasomes. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.|||Mice are viable and show no obvious developmental abnormalities. They have reduced male fertility due to defects in spermatogenesis in meiotic spermatocytes and during the maturation of postmeiotic haploid spermatids. Testes are defective in core histone replacement.|||Nucleus|||Nucleus speckle|||Phosphorylated.|||The bromodomain-like (BRDL) region specifically recognizes and binds acetylated histones.|||cytosol http://togogenome.org/gene/10090:Spag5 ^@ http://purl.uniprot.org/uniprot/Q7TME2 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected in testis, but not in the other tissues tested.|||Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase. Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture. In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes. Involved in centriole duplication. Required for CDK5RAP22, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2. In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis. May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (By similarity).|||Expression is cell cycle-regulated, with an increase from prophase to cytokinesis and return to basal levels at the next G1 phase.|||Homodimer, with a globular head domain and a long stalk. Homooligomer; the globular head domains associate, resulting in aster-like structures. Binds to microtubules in the mitotic spindle. Interacts with DCLRE1B/Apollo. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with KNSTRN. Interacts with RPTOR; this interaction competes with RPTOR binding to MTOR, resulting in decreased mTORC1 formation. Interacts with G3BP1. The complex formed with G3BP1 and RPTOR is increased by oxidative stress. Interacts with OSBPL8, PCM1 and CDK5RAP2. Interacts (via C-terminus) with NUMA1 (via C-terminus); this interaction promotes the recruitment of SPAG5 to the microtubules at spindle poles in a dynein-dynactin-dependent manner. Interacts with DYNLL1 (By similarity).|||Midbody|||Phosphorylated by AURKA.|||centriolar satellite|||centrosome|||kinetochore|||spindle|||spindle pole http://togogenome.org/gene/10090:Cpsf3 ^@ http://purl.uniprot.org/uniprot/Q3UDS1|||http://purl.uniprot.org/uniprot/Q9QXK7 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF3 subfamily.|||Binds 2 Zn(2+) ions per subunit.|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as mRNA 3'-end-processing endonuclease. Also involved in the histone 3'-end pre-mRNA processing. U7 snRNP-dependent protein that induces both the 3' endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner. Required for the selective processing of microRNAs (miRNAs) during embryonic stem cell differentiation via its interaction with ISY1 (PubMed:26255770, PubMed:29804889). Required for entering/progressing through S-phase of the cell cycle (By similarity). Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (PubMed:26255770). Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (PubMed:29804889).|||Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of CPSF1, CPSF2, CPSF3, CPSF4 and FIP1L1. Interacts with CPSF2, CSTF2 and SYMPK. Interacts with TUT1; the interaction is direct and mediates the recruitment of the CPSF complex on the 3'UTR of pre-mRNAs. Interacts with WDR33 (By similarity). Interacts with ZC3H3 (PubMed:16115198). Interacts with ISY1; this interaction is in an RNA independent manner (PubMed:26255770). Interacts with the microprocessor complex subunits DGCR8 and DROSHA; this interaction is in an RNA dependent manner (PubMed:26255770).|||Nucleus|||Sumoylated on Lys-462, Lys-465 and Lys-545, preferentially by SUMO3. http://togogenome.org/gene/10090:Pde6b ^@ http://purl.uniprot.org/uniprot/P23440 ^@ Cofactor|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Abolishes the retinal photoreceptor layer, outer nuclear layer, and outer plexiform layer in the retinal ultrastructure (PubMed:30240620). Loss of Opn1sw, Opn1mw and Rho expression in the retina (PubMed:30240620). Reduced rate of circadian photoentrainment, UVA and orange light-induced phase-shift response and Fos expression in the suprachiasmatic nuclei (SCN) in the brain (PubMed:30240620). Pde6b and Opn5 double knockout mice also show loss of retinal ultrastructures and a more severe reduction in the rate of circadian photoentrainment, light-induced phase-shift response and Fos expression in the SCN (PubMed:30240620).|||Belongs to the cyclic nucleotide phosphodiesterase family.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.|||Defects in Pde6b are the cause of the retinal degeneration (rd) allele, which is characterized by retinal degeneration (PubMed:1977087, PubMed:1656438). The retinal degeneration 1 (rd1) allele also contains a cofounding mutation in the Gpr179 gene (PubMed:25613321).|||Membrane|||Oligomer composed of two catalytic chains (alpha and beta), an inhibitory chain (gamma) and the delta chain.|||Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3',5'-cyclic GMP (By similarity). Necessary for the formation of a functional phosphodiesterase holoenzyme (PubMed:1847109). Involved in retinal circadian rhythm photoentrainment via modulation of UVA and orange light-induced phase-shift of the retina clock (PubMed:30240620). May participate in processes of transmission and amplification of the visual signal (By similarity).|||photoreceptor outer segment http://togogenome.org/gene/10090:Or10ad1c ^@ http://purl.uniprot.org/uniprot/E9Q1P2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tpcn1 ^@ http://purl.uniprot.org/uniprot/Q9EQJ0 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. Two pore calcium channel subfamily.|||Dimer. Interacts with MTOR; the interaction is required for TPCN1 ATP sensitivity (By similarity). Interacts with STX7, STX8 and STX12 (PubMed:28855648). Interacts with JPT2 (By similarity). Found in a complex with LSM12, TPCN1 and TPCN2 (By similarity).|||Each of the two internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.|||Early endosome membrane|||Endosome membrane|||Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a voltage-gated highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) that senses pH changes and confers electrical excitability to organelles (PubMed:24776928, PubMed:23394946, PubMed:23063126). Localizes to the early and recycling endosomes membranes where it plays a role in the uptake and processing of proteins and regulates organellar membrane excitability, membrane trafficking and pH homeostasis (PubMed:28855648). Ion selectivity is not fixed but rather agonist-dependent and under defined ionic conditions, can be readily activated by both NAADP and PI(3,5)P2 (By similarity). Required for mTOR-dependent nutrient sensing (PubMed:23394946).|||Lysosome membrane|||Mainly expressed in epithelial tissues like lung, kidney, colon, spleen and liver (at protein level).|||N-glycosylated.|||Na(+) current is inhibited by ATP in a MTORC-dependent manner. ATP sensitivity is independent of PI(3,5)P2 (By similarity). Probably regulated by Mg(2+) ions, cytosolic Mg(2+) selectively inhibits outward current while lysosomal Mg(2+) modestly inhibits both the outward and inward currents. In the absence of Mg(2+), NAADP readily activates TPCN2, with properties similar to PI(3,5)P2 (By similarity). Both current elicited by PI(3,5)P2 as well as NAADP are inhibited by tetrandrine (By similarity).|||Recycling endosome membrane|||TPCN1 and TPCN2 double knockouts are viable, fertile, have no obvious morphological abnormalities, and no obvious behavioral defects. After fasting for 3 days, they are less active and endurance performance is reduced by 8.3 fold in contrast to wild-type littermates that show no changes. Two days after re-introduction of food, mutants regain endurance and become as active as before fasting. http://togogenome.org/gene/10090:Gpc1 ^@ http://purl.uniprot.org/uniprot/Q3U379|||http://purl.uniprot.org/uniprot/Q9QZF2 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glypican family.|||Cell membrane|||Cell surface proteoglycan that bears heparan sulfate. Binds, via the heparan sulfate side chains, alpha-4 (V) collagen and participates in Schwann cell myelination (By similarity). May act as a catalyst in increasing the rate of conversion of prion protein PRPN(C) to PRNP(Sc) via associating (via the heparan sulfate side chains) with both forms of PRPN, targeting them to lipid rafts and facilitating their interaction. Required for proper skeletal muscle differentiation by sequestering FGF2 in lipid rafts preventing its binding to receptors (FGFRs) and inhibiting the FGF-mediated signaling. Binds Cu(2+) or Zn(2+) ions.|||Cell surface proteoglycan.|||Endosome|||N- and O-glycosylated. N-glycosylation is mainly of the complex type containing sialic acid. O-glycosylated with heparan sulfate. The heparan sulfate chains can be cleaved either by the action of heparanase or, degraded by a deaminative process that uses nitric oxide (NO) released from the S-nitrosylated cysteines. This process is triggered by ascorbate, or by some other reducing agent, in a Cu(2+)- or Zn(2+) dependent manner. Cu(2+) ions are provided by ceruloproteins such as APP, PRNP or CP which associate with GCP1 in intracellular compartments or lipid rafts.|||Null mice with induced pancreatic ductal adenocarcinomas (PDACs) exhibit attenuated pancreatic tumor growth and invasiveness, decreased cancer cell proliferation and mitogen-activated protein kinase activation. Pancreatic cancer cells isolated from the tumors of GPC1 (-/-) mice were not as invasive in response to fibroblast growth factor-2 (FGF-2) as cancer cells isolated from wild-type mice.|||S-nitrosylated in a Cu(2+)-dependent manner. Nitric acid (NO) is released from the nitrosylated cysteines by ascorbate or by some other reducing agent, in a Cu(2+) or Zn(2+) dependent manner. This free nitric oxide is then capable of cleaving the heparan sulfate side chains.|||This cell-associated glypican is further processed to give rise to a medium-released species.|||extracellular space http://togogenome.org/gene/10090:Klhl11 ^@ http://purl.uniprot.org/uniprot/Q8CE33 ^@ Function|||Subunit ^@ Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation.|||Homodimer. Interacts with CUL3. Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex (By similarity). http://togogenome.org/gene/10090:Fes ^@ http://purl.uniprot.org/uniprot/P16879 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated on Tyr-713 in response to FGF2. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Golgi apparatus|||Homooligomer. Interacts with BCR. Interacts (when activated, via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with phosphorylated KIT. Interacts with FLT3. Interacts (via F-BAR domain) with soluble tubulin. Interacts (via SH2 domain) with microtubules (By similarity).|||In a BRAF V600E-driven, PTEN deficient and FES deficient melanoma model, tumor growth is accelerated due to an increased proliferation of melanoma cells.|||Kinase activity is tightly regulated. Activated in response to signaling from a cell surface receptor. Activation probably requires binding of a substrate via the SH2 domain, plus autophosphorylation at Tyr-713. Present in an inactive form in the absence of activating stimuli.|||No visible phenotype. Mice are fertile and healthy, display slightly reduced numbers of myeloid cells and are more sensitive to lipopolysaccharide (LPS). Mice lacking both Fps/Fes and Fer activity are viable and fertile, but produce fewer offspring than normal. They display elevated levels of circulating neutrophils, erythrocytes and platelets, while other cell counts are normal.|||The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.|||The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins (By similarity).|||Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28.|||cytoskeleton|||cytosol|||focal adhesion http://togogenome.org/gene/10090:Larp7 ^@ http://purl.uniprot.org/uniprot/Q05CL8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LARP7 family.|||Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1) (By similarity). Interacts with METTL16 (By similarity). Interacts with RBM7; upon genotoxic stress this interaction is enhanced, triggering the release of inactive P-TEFb complex from the core, yielding to P-TEFb complex activation (By similarity). Associates with box C/D small nucleolar ribonucleoprotein (snoRNP) complexes (PubMed:32017896).|||Embryonic lethality between embryonic day 17.5 dpc and birth (PubMed:23154982). Conditional knockout mice lacking Larp7 in germline cells show defects in spermatogenesis: males are sterile, whereas all females display normal fertility (PubMed:32017896). Cells show reduced 2'-O-methylation of U6 snRNAs and defects in mRNA splicing (PubMed:32017896).|||Preferentially expressed in primordial germ cells (PubMed:23154982). Ubiquitously expressed in the embryo (PubMed:22865833).|||RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function (PubMed:32017896). Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II (By similarity). The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (By similarity). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (By similarity). LARP7 specifically binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex (By similarity). LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing (PubMed:32017896). Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes (PubMed:32017896). U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (PubMed:32017896). Binds U6 snRNAs with a 5'-CAGGG-3' sequence motif (By similarity). U6 snRNA processing is required for spermatogenesis (PubMed:32017896).|||The xRRM domain binds the 3' end of 7SK snRNA (7SK RNA) at the top of stem-loop 4.|||nucleoplasm http://togogenome.org/gene/10090:Sstr3 ^@ http://purl.uniprot.org/uniprot/P30935 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Homodimer and heterodimer with SSTR2. Heterodimerization with SSTR2 inactivates SSTR3 receptor function (By similarity).|||In the brain, primarily observed in the forebrain. Moderate levels found throughout laminae 2-6 of the neocortex and allocortex, and high levels in lamina 2 of the piriform and entorhinal cortices. High levels also present in the cornu ammonis fields of the hippocampus. In the amygdala, highly expressed in the nucleus of the lateral olfactory tract with expression also detected in the rostral portions of the basal magnocellular and lateral nuclei. In the diencephalon, moderate levels observed in the ventromedial and arcuate nuclei of the hypothalamus. In the midbrain, moderate levels found in the lateral portion of the substantia nigra pars reticulata.|||Phosphorylated. Phosphorylation increases upon somatostatin binding (By similarity).|||Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. http://togogenome.org/gene/10090:Dhx30 ^@ http://purl.uniprot.org/uniprot/Q99PU8 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Cytoplasm|||Detected at low levels of expression at 3.5 and 6.5 days post coitum (dpc). At 7.5 dpc, it is detected in the ectoderm, mesoderm, and ectoplacental cone. By 8.5 dpc, expression is increased, specifically in the central nervous system, neural plate, and neural tube, which remains constant until 10.5 dpc where it decreases. By 11.5 to 15.5 dpc, expression is reduced further in the central nervous system.|||Expressed in the heart, brain, spleen, lung, liver, skeletal muscle, kidney, and testis. Expression is strongest in the testis and brain, while the lowest levels of expression are found in the spleen and lung.|||Identified in a complex with TFAM and SSBP1. Interacts (via N-terminus) with ZC3HAV1 (via N-terminal domain) in an RNA-independent manner. Found in a complex with GRSF1, DDX28, FASTKD2 and FASTKD5.|||Mitochondrion|||Phosphorylated on Ser-15.|||RNA-dependent helicase (PubMed:25219788). Plays an important role in the assembly of the mitochondrial large ribosomal subunit (By similarity). Required for optimal function of the zinc-finger antiviral protein ZC3HAV1 (By similarity). Associates with mitochondrial DNA (By similarity). Involved in nervous system development and differentiation through its involvement in the up-regulation of a number of genes which are required for neurogenesis, including GSC, NCAM1, neurogenin, and NEUROD (PubMed:25219788).|||mitochondrion nucleoid http://togogenome.org/gene/10090:Eda ^@ http://purl.uniprot.org/uniprot/A0A0U5J8Q0|||http://purl.uniprot.org/uniprot/O54693|||http://purl.uniprot.org/uniprot/Q1L2D8|||http://purl.uniprot.org/uniprot/Q1L2D9|||http://purl.uniprot.org/uniprot/Q1L2E0|||http://purl.uniprot.org/uniprot/Q3UV69 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cell membrane|||Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Functions as a ligand activating the DEATH-domain containing receptors EDAR and EDA2R. Isoform TAA binds only to the receptor EDAR, while isoform TA-A2 binds exclusively to the receptor EDA2R (By similarity). May also play a role in cell adhesion (PubMed:10534613).|||Defects in Eda are the cause of the tabby phenotype in mice (the equivalent of anhidrotic ectodermal dysplasia in humans). The disease is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.|||Homotrimer. The homotrimers may then dimerize and form higher-order oligomers.|||Isoform TA-A2 binds exclusively to the receptor EDA2R.|||Isoform TAA binds only to the receptor EDAR, while isoform TA-A2 binds exclusively to the receptor EDA2R.|||N-glycosylated.|||Processing by furin produces a secreted form.|||Secreted http://togogenome.org/gene/10090:Snx11 ^@ http://purl.uniprot.org/uniprot/Q91WL6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Endosome|||Membrane|||Monomer.|||Phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes.|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate. http://togogenome.org/gene/10090:Or51aa2 ^@ http://purl.uniprot.org/uniprot/L7N462 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pigo ^@ http://purl.uniprot.org/uniprot/A2AG36|||http://purl.uniprot.org/uniprot/Q562G0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PIGG/PIGN/PIGO family. PIGO subfamily.|||Endoplasmic reticulum membrane|||Membrane http://togogenome.org/gene/10090:Scarf2 ^@ http://purl.uniprot.org/uniprot/P59222|||http://purl.uniprot.org/uniprot/Q58A84 ^@ Caution|||Function|||Subcellular Location Annotation|||Subunit ^@ Homophilic and heterophilic interaction via its extracellular domain. Interacts with SCARF1. The heterophilic interaction with SCARF1, which is stronger than the homophilic interaction with itself, is suppressed by the presence of SCARF1 ligand such as Ac-LDL.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Probable adhesion protein, which mediates homophilic and heterophilic interactions. In contrast to SCARF1, it poorly mediates the binding and degradation of acetylated low density lipoprotein (Ac-LDL). http://togogenome.org/gene/10090:Bhlha9 ^@ http://purl.uniprot.org/uniprot/Q5RJB0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ At 10.5 dpc, expressed in forelimb and hindlimb buds, in the distal mesenchyme below the apical ectodermal ridge. At 11.5 dpc, expression is restricted to the subridge mesenchymal layer, as well as in the dorsal and ventral regions of the developing limbs.|||Heterodimer. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with TCF3, TCF4, and TCF12.|||Nucleus|||Transcription factor, which play a role in limb development. Is an essential player in the regulatory network governing transcription of genes implicated in limb morphogenesis. http://togogenome.org/gene/10090:Nprl2 ^@ http://purl.uniprot.org/uniprot/Q9WUE4 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NPR2 family.|||Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:26166573, PubMed:29768191). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (By similarity). In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2 (By similarity). Within the GATOR1 complex, NPRL2 constitutes the catalytic subunit that mediates the GAP activity (By similarity).|||Embryonic lethality due to defective fetal liver hematopoiesis (PubMed:26166573). Embryos also display reduced methionine levels (PubMed:26166573). Lysosomal acidification is impaired, leading to defective lysosomal processing of cobalamin and methionine synthase (PubMed:26166573). Conditional deletion in skeletal muscle causes constitutive activation of mTORC1 signaling: muscle fibers are significantly larger and show altered fiber-type composition, with more fast-twitch glycolytic and fewer slow-twitch oxidative fibers (PubMed:29768191). Mice with a conditional deletion in muscle also have altered running behavior and enhanced glucose tolerance (PubMed:29768191).|||In the presence of abundant amino acids, ubiquitinated at Lys-158 and Lys-357 via 'Lys-6'-linked ubiquitination by the WDR24 component of the GATOR2 complex, thereby inhibiting the GATOR1 complex and promoting mTORC1 activation.|||Lysosome membrane|||Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues. May act as a tumor suppressor. Suppresses cell growth and enhances sensitivity to various anticancer drugs.|||The arginine finger is critical for the GTPase-activating mechanism.|||Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3. GATOR1 mediates the strong interaction of the GATOR complex with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) heterodimers. GATOR1 interacts with GPR155/LYCHOS; interaction takes place in presence of cholesterol and prevents interaction between GATOR1 and KICSTOR. Interacts with PDPK1. http://togogenome.org/gene/10090:Plcxd3 ^@ http://purl.uniprot.org/uniprot/Q8BLJ3 ^@ Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Widely expressed, with highest levels in brain, followed by heart atrium. Not detected in small intestine, nor stomach. http://togogenome.org/gene/10090:Anapc5 ^@ http://purl.uniprot.org/uniprot/A0A0G2JDE8|||http://purl.uniprot.org/uniprot/A0A0G2JDM7|||http://purl.uniprot.org/uniprot/A0A0G2JE03|||http://purl.uniprot.org/uniprot/Q3TWF7|||http://purl.uniprot.org/uniprot/Q3U5Y4|||http://purl.uniprot.org/uniprot/Q3U981|||http://purl.uniprot.org/uniprot/Q3UFC2|||http://purl.uniprot.org/uniprot/Q8BTZ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the APC5 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.|||Nucleus|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.|||spindle http://togogenome.org/gene/10090:Btk ^@ http://purl.uniprot.org/uniprot/P35991 ^@ Activity Regulation|||Cofactor|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation. In primary B lymphocytes, is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug acting as a tyrosine kinase inhibitor, also blocks BTK activity.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.|||Binds 1 zinc ion per subunit.|||Cell membrane|||Cytoplasm|||Defects in Btk are the cause of murine X-linked immunodeficiency (XID).|||Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-551 by LYN and SYK. Phosphorylation at Tyr-551 is followed by autophosphorylation of Tyr-223 which may create a docking site for a SH2 containing protein. Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction. Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes it's recruitment (By similarity).|||Membrane raft|||Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:7538439, PubMed:8629002, PubMed:10852954). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (By similarity). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (By similarity). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (By similarity). Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:17725607). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (By similarity). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (By similarity). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (By similarity). BTK also plays a critical role in transcription regulation (By similarity). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (By similarity). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (By similarity). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:11120822, PubMed:16738337). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:11120822, PubMed:16738337). ARID3A and NFAT are other transcriptional target of BTK (PubMed:11120822, PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:11120822, PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:11120822, PubMed:16738337). BTK has a dual role in the regulation of apoptosis (By similarity).|||Nucleus|||Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain. Interacts with ARID3A, CAV1, FASLG, PIN1, TLR8 and TLR9.|||Prevents BCR-induced activation of NF-kappa-B.|||The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain. http://togogenome.org/gene/10090:Brip1 ^@ http://purl.uniprot.org/uniprot/Q5SXJ3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DEAD box helicase family. DEAH subfamily.|||Binds 1 [4Fe-4S] cluster.|||Binds directly to the BRCT domains of BRCA1. Interacts with the CIA complex components CIAO1, CIAO2B and MMS19.|||Cytoplasm|||DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. Acts late in the 'Fanconi anemia' pathway, after FANCD2 ubiquitination. Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Mt1 ^@ http://purl.uniprot.org/uniprot/A0A1D5RLN7|||http://purl.uniprot.org/uniprot/P02802 ^@ Domain|||Function|||Similarity ^@ Belongs to the metallothionein superfamily. Type 1 family.|||Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.|||Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids. http://togogenome.org/gene/10090:Mamld1 ^@ http://purl.uniprot.org/uniprot/P0C6A2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mastermind family.|||Nucleus|||Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ (By similarity). Required for testosterone production. http://togogenome.org/gene/10090:Ehd3 ^@ http://purl.uniprot.org/uniprot/Q9QXY6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes tubulation of endocytic membranes (By similarity). Binding to phosphatidic acid induces its membrane tubulation activity (PubMed:26896729). Plays a role in endocytic transport. Involved in early endosome to recycling endosome compartment (ERC), retrograde early endosome to Golgi, and endosome to plasma membrane (rapid recycling) protein transport. Involved in the regulation of Golgi maintenance and morphology (By similarity). Involved in the recycling of internalized D1 dopamine receptor (By similarity). Plays a role in cardiac protein trafficking probably implicating ANK2. Involved in the ventricular membrane targeting of SLC8A1 and CACNA1C and probably the atrial membrane localization of CACNA1GG and CACNA1H implicated in the regulation of atrial myocyte excitability and cardiac conduction (PubMed:20489164, PubMed:24759929, PubMed:25825486). In conjunction with EHD4 may be involved in endocytic trafficking of KDR/VEGFR2 implicated in control of glomerular function (PubMed:21408024). Involved in the rapid recycling of integrin beta-3 implicated in cell adhesion maintenance (By similarity). Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating a function in neuronal APP processing. Plays a role in the formation of the ciliary vesicle, an early step in cilium biogenesis; possibly sharing redundant functions with Ehd1 (PubMed:25686250).|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Homooligomer. Heterooligomer with EHD1 (PubMed:12121420). Heterooligomer with EHD2 and EHD4; ATP-binding is required for heterooligomerization (By similarity). Interacts with PACSIN1 (PubMed:15930129). Interacts with PACSIN2 (PubMed:15930129). Interacts (via EH domain) with MICALL1 (By similarity). Interacts (via EH domain) with RAB11FIP2 (By similarity). Interacts with ANK2 (By similarity). Interacts with CACNA1GG and CACNA1H (PubMed:25825486).|||Recycling endosome membrane|||Strong expression seen in the kidney, brain and liver. In the kidney, expressed exclusively by glomerular endothelial cells; at protein level. Expressed in skeletal muscle neuromuscular junction perisynaptic region; at protein level.|||The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.|||cilium membrane http://togogenome.org/gene/10090:Pofut1 ^@ http://purl.uniprot.org/uniprot/Q91ZW2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 65 family.|||Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).|||Early embryos of null mice are defective in somitogenesis. At 8.5 dpc, embryos are of normal size and appearance but somites adjacent to the presomitic mesoderm (PSM) are fused. In 8.25 dpc embryos, expression of NOTCH target genes such as HES5 and JAG1 as well as LFNG and UNCX4.1 is severely reduced in somites. There is up-regulation of a number of these genes such as HES5 and LFNG as well as DLL1 and NOTCH1 in the neural tube and brain. Mice die at midgestation with severe defects in somitogenesis, vasculogenesis, cardiogenesis and neurogenesis.|||Endoplasmic reticulum|||Increased expression throughout embryo development. Ubiquitous expression at 9.5 dpc and 11.5 dpc with lower expression at 9.5 dpc.|||N-glycosylated.|||The cax (compact axial skeleton) spontaneous mutation is a hypomorphic allele that reduces Pofut1 expression and protein levels leading to reduced Notch signaling. cax mutant embryos have somites of variable size, partly abnormal Lfng expression, defective anterior-posterior somite patterning and abnormal axial skeleton development. Mice have kinky and shortened tails and shortened body length (PubMed:19161597). http://togogenome.org/gene/10090:Cd84 ^@ http://purl.uniprot.org/uniprot/Q18PI6 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Homodimer; via its extracellular domain. Forms a head to tail dimer with a CD48 molecule from another cell. Interacts with SH2 domain-containing proteins SH2D1A/SAP and SH2D1B/EAT-2. Interacts with tyrosine-protein phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 via its phosphorylated cytoplasmic domain, and this interaction is blocked by SH2D1A (By similarity).|||N-glycosylated.|||Phosphorylated by tyrosine-protein kinase LCK on tyrosine residues following ligation induced by agonist monoclonal antibody. The association with SH2D1A/SAP is dependent of tyrosine phosphorylation of its cytoplasmic domain. Phosphorylated on Tyr-280 and Tyr-300 following platelet aggregation. Phosphorylated on tyrosine residues upon high affinity immunoglobulin epsilon receptor aggregation in mast cells.|||Predominantly expressed in hematopoietic tissues such as lymph node, spleen, thymus, and bone marrow. Detected also in lung.|||Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2 (PubMed:20962259). Can mediate natural killer (NK) cell cytotoxicity dependent on SH2D1A and SH2D1B (PubMed:20962259). Increases proliferative responses of activated T-cells and SH2D1A/SAP does not seen be required for this process. Homophilic interactions enhance interferon gamma/IFNG secretion in lymphocytes and induce platelet stimulation via a SH2D1A/SAP-dependent pathway. May serve as a marker for hematopoietic progenitor cells (By similarity). Required for a prolonged T-cell:B-cell contact, optimal T follicular helper function, and germinal center formation (PubMed:20153220). In germinal centers involved in maintaining B cell tolerance and in preventing autoimmunity (PubMed:25801429). In mast cells negatively regulates high affinity immunoglobulin epsilon receptor signaling; independent of SH2D1A and SH2D1B but implicating FES and PTPN6/SHP-1 (By similarity). In macrophages enhances LPS-induced MAPK phosphorylation and NF-kappaB activation and modulates LPS-induced cytokine secretion; involving ITSM 2 (PubMed:20628063). Positively regulates macroautophagy in primary dendritic cells via stabilization of IRF8; inhibits TRIM21-mediated proteasomal degradation of IRF8 (By similarity).|||The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containingbinding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. A 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). http://togogenome.org/gene/10090:Fitm2 ^@ http://purl.uniprot.org/uniprot/P59266 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the FIT family.|||Endoplasmic reticulum membrane|||Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate (By similarity). Preferentially hydrolyzes unsaturated long-chain acyl-CoA substrates such as oleoyl-CoA/(9Z)-octadecenoyl-CoA and arachidonoyl-CoA/(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA in the endoplasmic reticulum (ER) lumen (By similarity). This catalytic activity is required for maintaining ER structure and for lipid droplets (LDs) biogenesis, which are lipid storage organelles involved in maintaining lipid and energy homeostasis (PubMed:18160536, PubMed:26504167) (By similarity). Directly binds to diacylglycerol (DAGs) and triacylglycerol, which is also important for LD biogenesis (PubMed:22106267) (By similarity). May support directional budding of nacent LDs from the ER into the cytosol by reducing DAG levels at sites of LD formation (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity).|||Homozygous knockout mice display embryonic lethality (PubMed:30923760). Heterozygous knockout mice exhibit shortened left ventricular end-diastolic dimension and shortened left ventricular end-systolic dimension (PubMed:30923760). They also exhibit improved profiles upon pressure overload-induced heart failure (PubMed:30923760).|||Widely expressed, with highest levels in white and brown adipose tissues (at protein level). In the heart, mRNA expression levels do not correlate well with protein levels, suggesting post-transcriptional regulation in this organ. http://togogenome.org/gene/10090:Dynlrb2 ^@ http://purl.uniprot.org/uniprot/Q9DAJ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.|||Belongs to the GAMAD family.|||Homodimer (Probable). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1I1 and DYNC1I2. Self-associates. Interacts with DYNLRB1 (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Taf11 ^@ http://purl.uniprot.org/uniprot/Q99JX1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF11 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts with TAF13 both in vitro and intracellularly; also interacts directly with TBP.|||Nucleus|||TBP and TAFII18 bind to distinct domains of TAFII28.|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. TAF11, together with TAF13 and TBP, play key roles during promoter binding by the TFIID and TFIIA transcription factor complexes. http://togogenome.org/gene/10090:Magoh ^@ http://purl.uniprot.org/uniprot/P61327 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the mago nashi family.|||Cytoplasm|||Heterodimer with RBM8A. Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A. Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro). Identified in the spliceosome C complex.|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the spliceosome. Plays a redundant role with MAGOHB as core component of the exon junction complex (EJC) and in the nonsense-mediated decay (NMD) pathway. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms; the function is different from the established EJC assembly.|||Ubiquitous. Detected in brain, heart, liver, lung, spleen and testis. http://togogenome.org/gene/10090:Map6 ^@ http://purl.uniprot.org/uniprot/Q7TSJ2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the STOP family.|||Golgi apparatus|||Interacts with calmodulin (via C-terminus); the interaction is dependent on Ca(2+) (PubMed:14516200). Interacts (via C-terminus) with TMEM106B (via N-terminus) (By similarity). Interacts with ZDHHC13 (via ANK repeats) (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:26198635).|||Involved in microtubule stabilization in many cell types, including neuronal cells (PubMed:9600916). Specifically has microtubule cold stabilizing activity (PubMed:9600916). Involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with TMEM106B (By similarity). Regulates KIF5A-mediated axonal cargo transport (By similarity). Regulates axonal growth during neuron polarization (PubMed:28521134).|||Isoform 1 is specifically expressed in adult brain. Isoform 2 is predominantly expressed in embryonic brain; expression persists at low levels in the adult brain. Isoform 3 is expressed at high levels in lung and at lower levels in testis, heart, muscle and kidney (at protein level). Oligodendrocytes express a major isoform of 89 kDa (O-STOP). Astrocytes also express an isoform of 60 kDa (A-STOP).|||Isoform 2 is expressed in embryonic brain.|||Mice are devoid of cold-stable microtubules and show no detectable defects in brain anatomy but show synaptic defects, with depleted synaptic vesicle pools and impaired synaptic plasticity, associated with severe behavioral disorders, including a disorganized activity with disruption of normal behavioral sequences and episodes of hyperlocomotion or apparent prostration, anxiety, severe social withdrawal and complete nurturing defects (PubMed:12231625). The behavioral defects are alleviated by long-term treatment with neuroleptics (PubMed:12231625). RNAi-mediated knockdown in brain at the 14.5 dpc stage disrupts proper neuron migration resulting in their accumulation in the ventricular and subventricular zones (PubMed:28521134).|||Palmitoylated. Probably depalmitoylated by ABHD17A, ABHD17B and ABHD17C. During neuronal polarization, palmitoylation and depalmitoylation cycles regulate MAP6 shuttling between secretory vesicles and microtubules, and its polarized distribution in the axon.|||Produced by alternative promoter usage.|||Produced by alternative splicing of isoform 1.|||axon|||cytoskeleton|||dendrite|||secretory vesicle membrane http://togogenome.org/gene/10090:Or51ag1 ^@ http://purl.uniprot.org/uniprot/E9Q598 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ube2h ^@ http://purl.uniprot.org/uniprot/P62257|||http://purl.uniprot.org/uniprot/Q3V2N4 ^@ Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. E2 ubiquitin conjugating enzyme that transfers ubiquitin to MAEA, a core component of the CTLH E3 ubiquitin-protein ligase complex. In vitro catalyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitination. Capable, in vitro, to ubiquitinate histone H2A.|||Autoubiquitinated in vitro in the presence of NEDD4L.|||Belongs to the ubiquitin-conjugating enzyme family.|||Detected in reticulocytes, lung, brain and skeletal muscle (at protein level) (PubMed:7761435). Ubiquitous. Detected in cardiac muscle, brain, spleen, lung, liver, skeletal muscle, kidney andmso testis (PubMed:7590289).|||Interacts with MAEA and WDR26, components of the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. http://togogenome.org/gene/10090:Foxa1 ^@ http://purl.uniprot.org/uniprot/P35582 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds DNA as a monomer. Interacts with FOXA2. Interacts with NKX2-1. Interacts with HDAC7. Interacts with the histone H3-H4 heterodimer. Associates with nucleosomes containing histone H2A. Interacts with AR. Interacts with NR0B2 (By similarity).|||Most abundant in midgestation embryos (day 9.5). In embryonic lung expressed at 12 dpc and 18 dpc with highest levels in proximal airways and lowest levels in the distal lung.|||Nucleus|||Restricted mainly to endoderm-derived tissues (lung, liver, stomach, and small intestine). Expressed in the prostate.|||The prostate shows a severely altered ductal pattern that resembles primitive epithelial cords surrounded by thick stromal layers; no differentiated or mature luminal epithelial cells are found. Dehydration and electrolyte imbalance, development of mild nephrogenic diabetes insipidus. Severe hypoglycemia due to at least in part diminished expression of GCG. Mice deficient for Fox1a and deficient for Foxa2 in the endoderm from 8.5 dpc onwards do not show hepatic bud formation. Mice deficient for Fox1a and deficient for Foxa2 in the midbrain from 10.5 dpc onwards show almost complete loss of mDA neurons. Mice deficient for Fox1a and deficient for Foxa2 in the embryonic liver show hyperplasia of the biliary tree due to at least in part activation of IL-6 expression, a proliferative signal for cholangiocytes.|||Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3' (By similarity). Proposed to play a role in translating the epigenetic signatures into cell type-specific enhancer-driven transcriptional programs. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas, lungs and prostate; FOXA1 and FOXA2 seem to have at least in part redundant roles. Plays a role in prostate morphogenesis and epithelial cell differentiation. FOXA1 and FOXA2 are essential for hepatic specification. FOXA1 and FOXA2 are required for morphogenesis and cell differentiation during formation of the lung. FOXA1 and FOXA2 are involved in bile duct formation; they positively regulate the binding of glucocorticoid receptor/NR3C1 to the IL6 promoter. FOXA1 and FOXA2 regulate multiple phases of midbrain dopaminergic neuron development; they regulate expression of NEUROG2 at the beginning of mDA neurogenesis and of NR4A2 and EN1 in immature mDA neurons. Modulates the transcriptional activity of nuclear hormone receptors. Is involved in ESR1-mediated transcription. Inhibits NKX2-1-mediated transcription from the SFTPC promoter in lung epithel independently from DNA-binding. Involved in regulation of apoptosis. Involved in cell cycle regulation. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; activates the GCG promoter. http://togogenome.org/gene/10090:Slc20a1 ^@ http://purl.uniprot.org/uniprot/Q61609 ^@ Developmental Stage|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ (Microbial infection) May function as a retroviral receptor but do not confer infection susceptibility to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B).|||Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.|||By growth hormone.|||Cell membrane|||Detected at 17 dpc of embryonic development in a subpopulation of early hypertrophic chondrocytes in bone, but not when fully differentiated.|||Intron retention. The sequence differs at the 3'end due to intron retention.|||Region A does not confer susceptibility to infection by Gibbon Ape Leukemia Virus (GaLV) and Feline leukemia virus subgroup B (FeLV-B). Substitution of Human SLC20A1 region A by region A of murine SLC20A1 prevents viral infection.|||Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion. May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification. Essential for cell proliferation but this function is independent of its phosphate transporter activity.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Trmt2a ^@ http://purl.uniprot.org/uniprot/E9PUQ7|||http://purl.uniprot.org/uniprot/Q8BNV1 ^@ Caution|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.|||Htf9a (RanBP1) and Trmt2a are transcribed with opposite polarity from complementary DNA strands from a shared bidirectional TATA-less promoter.|||In a cell-cycle manner (PubMed:9224656, PubMed:9417108). Transcription is activated at the G1/S transition of the cell cycle and peaks in S phase, while being repressed in quiescent tissues and growth-arrested cells (PubMed:9417108).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and some mRNAs. Mainly catalyzes the methylation of uridine at position 54 (m5U54) in cytosolic tRNAs. Also able to mediate the formation of 5-methyl-uridine in some mRNAs.|||Widely expressed at low level. Expressed at higher level in proliferating cells.|||cytosol http://togogenome.org/gene/10090:Il4 ^@ http://purl.uniprot.org/uniprot/P07750 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-4/IL-13 family.|||Cytokine secreted primarily by mast cells, T-cells, eosinophils, and basophils that plays a role in regulating antibody production, hematopoiesis and inflammation, and the development of effector T-cell responses (PubMed:3083412). Induces the expression of class II MHC molecules on resting B-cells (PubMed:3498301). Enhances both secretion and cell surface expression of IgE and IgG1 (PubMed:3498301). Regulates also the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes (By similarity). Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4 (PubMed:26416964). In addition, plays a critical role in higher functions of the normal brain, such as memory and learning (PubMed:25772794, PubMed:28202615). Upon binding to IL4, IL4R receptor dimerizes either with the common IL2R gamma chain/IL2RG to produce the type 1 signaling complex, located mainly on hematopoietic cells, or with the IL13RA1 to produce the type 2 complex, which is expressed also on nonhematopoietic cells. Engagement of both types of receptors initiates JAK3 and to a lower extend JAK1 phosphorylation leading to activation of the signal transducer and activator of transcription 6/STAT6 (PubMed:8624821, PubMed:25847241).|||Deletion mutant mice demonstrate anxiety-like behavior in comparison to WT mice (PubMed:25772794). In addition, they show impaired cognitive function (PubMed:28202615).|||Interacts with IL4R. Interacts with IL13RA1.|||Secreted http://togogenome.org/gene/10090:Ntsr1 ^@ http://purl.uniprot.org/uniprot/A2ACT4|||http://purl.uniprot.org/uniprot/O88319 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Neurotensin receptor subfamily. NTSR1 sub-subfamily.|||Cell membrane|||G-protein coupled receptor for the tridecapeptide neurotensin (NTS). Signaling is effected via G proteins that activate a phosphatidylinositol-calcium second messenger system. Signaling leads to the activation of downstream MAP kinases and protects cells against apoptosis.|||Interacts (palmitoylated form) with GNA11.|||Membrane|||Membrane raft|||N-glycosylated.|||Palmitoylated; this is required for normal localization at membrane rafts and normal GNA11-mediated activation of down-stream signaling cascades. The palmitoylation level increases in response to neurotensin treatment.|||The ligand binding pocket consists mainly of extracellular loops ECL2 and ECL3, as well as transmembrane regions TM6 and TM7. http://togogenome.org/gene/10090:Or13p4 ^@ http://purl.uniprot.org/uniprot/Q8VFY3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tspyl3 ^@ http://purl.uniprot.org/uniprot/Q3UYP3|||http://purl.uniprot.org/uniprot/Q6PE20 ^@ Similarity ^@ Belongs to the nucleosome assembly protein (NAP) family. http://togogenome.org/gene/10090:Ccr8 ^@ http://purl.uniprot.org/uniprot/P56484|||http://purl.uniprot.org/uniprot/Q3ZB17 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in thymus.|||Membrane|||Receptor for the CCL1/SCY1/TCA-3 chemokine. http://togogenome.org/gene/10090:Zfp598 ^@ http://purl.uniprot.org/uniprot/Q80YR4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZNF598/HEL2 family.|||E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation, leading to degradation of nascent peptide chains. ZNF598 is activated when ribosomes are stalled within an mRNA following translation of prematurely polyadenylated mRNAs. Acts as a ribosome collision sensor: specifically recognizes and binds collided di-ribosome, which arises when a trailing ribosome encounters a slower leading ribosome, leading to terminally arrest translation. Following binding to colliding ribosomes, mediates monoubiquitination of 40S ribosomal proteins RPS10/eS10 and RPS3/uS3, and 'Lys-63'-linked polyubiquitination of RPS20/uS10. Polyubiquitination of RPS20/uS10 promotes recruitment of the RQT (ribosome quality control trigger) complex, which drives the disassembly of stalled ribosomes, followed by degradation of nascent peptides. E3 ubiquitin-protein ligase activity is dependent on the E2 ubiquitin-conjugating enzyme UBE2D3. Also acts as an adapter that recruits the 4EHP-GYF2 complex to mRNAs. Independently of its role in RQC, may also act as a negative regulator of interferon-stimulated gene (ISG) expression.|||Interacts with the E2 ubiquitin-conjugating enzyme UBE2D3. Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598.|||cytosol http://togogenome.org/gene/10090:Uri1 ^@ http://purl.uniprot.org/uniprot/Q3TLD5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RNA polymerase II subunit 5-mediating protein family.|||Cytoplasm|||Expressed in embryo at 6 dpc, onward.|||Expressed in the spinal cord, ganglia, choroid plexus and olfactors epithelium of the developing brain. Expressed in skin, lung, kidney, testis and muscles (at protein level). Expressed strongly in brain and kidney. Expressed weakly in skeletal muscle, lung and liver.|||Homodimer. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with POLR2E/RPB5, RUVBL2 and RUVBL1. Interacts with PFDN2, PFDN4 and STAP1; the interactions are phosphorylation-dependent and occur in a growth-dependent manner in the mitochondrion. Interacts with UXT. Interacts with PPP1CC; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts (via the middle C-terminal region) with GTF2F1 and GTF2F2. Interacts with DMAP1. Interacts with TSC1 and TSC2. Interacts with PRPF8 and EFTUD2 in a ZNHIT2-dependent manner.|||Involved in gene transcription regulation. Acts as a transcriptional repressor in concert with the corepressor UXT to regulate androgen receptor (AR) transcription. May act as a tumor suppressor to repress AR-mediated gene transcription and to inhibit anchorage-independent growth in prostate cancer cells. Required for cell survival in ovarian cancer cells. Together with UXT, associates with chromatin to the NKX3-1 promoter region (By similarity).|||Mitochondrion|||Nucleus|||Phosphorylation occurs in response to androgen treatment in prostate cancer cells in a mTOR-dependent manner. Phosphorylated; hyperhosphorylated in mitochondria in a mTORC-dependent signaling pathway. Phosphorylated at Ser-369 by RPS6KB1 in a growth factor- and rapamycin-dependent manner. S6K1-mediated mitochondrial phosphorylation at Ser-369 disrupts the URI1-PPP1CC complex in the mitochondrion, relieves PPP1CC phosphatase inhibition activity and hence engages a negative feedback diminishing RPS6KB1 kinase activity, preventing sustained S6K1-dependent signaling (By similarity). Phosphorylated. Phosphorylation occurs essentially on serine residues.|||Plays a central role in maintaining S6K1 signaling and BAD phosphorylation under normal growth conditions thereby protecting cells from potential deleterious effects of sustained S6K1 signaling. The URI1-PPP1CC complex acts as a central component of a negative feedback mechanism that counteracts excessive S6K1 survival signaling to BAD in response to growth factors. Mediates inhibition of PPP1CC phosphatase activity in mitochondria. Coordinates the regulation of nutrient-sensitive gene expression availability in a mTOR-dependent manner. Seems to be a scaffolding protein able to assemble a prefoldin-like complex that contains PFDs and proteins with roles in transcription and ubiquitination (By similarity).|||dendrite http://togogenome.org/gene/10090:Or8k30 ^@ http://purl.uniprot.org/uniprot/A2AK60 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5b108 ^@ http://purl.uniprot.org/uniprot/Q8VFW3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Prkcz ^@ http://purl.uniprot.org/uniprot/Q02956|||http://purl.uniprot.org/uniprot/Q3V341 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity). Isoform 2: Constitutively active (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase (By similarity).|||Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro (By similarity).|||Cell junction|||Cytoplasm|||Endosome|||Induced during synaptic long term potentiation.|||Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 (By similarity). Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDPK1 (via N-terminal region) (By similarity). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529). Interacts with VAMP2 (PubMed:17313651). Forms a complex with WDFY2 and VAMP2 (PubMed:17313651). Interacts with APPL1 (By similarity).|||Involved in late synaptic long term potentiation phase in CA1 hippocampal cells and long term memory maintenance.|||Isoform 1: In brain, highly expressed in cerebellar granule neurons and cerebellar astrocytes (at protein level) (PubMed:1487145, PubMed:12932816). Expressed at low levels in testes, lung and kidney (PubMed:1487145, PubMed:23283171). Isoform 2: Specifically expressed in brain where it localizes to cerebellar granule neurons (at protein level) (PubMed:12932816, PubMed:23283171).|||Membrane|||No visible phenotype (PubMed:23283171). Reduced anxiety-like behavior in males (PubMed:23283171). Does not affect long term memory maintenance (PubMed:23283171, PubMed:27187150). However, when the conditions during the establishment of memory are more demanding, spatial long term memory maintenance is slightly affected (PubMed:27187150). Up-regulation of PRKCI/PKCiota protein levels following induction of synaptic long term potentiation abnormally persist. This compensatory mechanism is responsible for the lack of defect in long term memory maintenance in absence of isoform 1 and isoform 2 (PubMed:27187150). Isoform 2: RNAi-mediated knockdown prevents late synaptic long term potentiation and spatial long term memory (PubMed:27187150).|||Produced by alternative promoter usage.|||The C1 domain does not bind the diacylglycerol (DAG).|||The PB1 domain mediate mutually exclusive interactions with SQSTM1 and PARD6B. http://togogenome.org/gene/10090:Crispld1 ^@ http://purl.uniprot.org/uniprot/Q8CGD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the CRISP family.|||Secreted http://togogenome.org/gene/10090:Smg1 ^@ http://purl.uniprot.org/uniprot/Q8BKX6 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated.|||Belongs to the PI3/PI4-kinase family.|||Component of the SMG1C complex composed of SMG1, SMG8 and SMG9; the recruitment of SMG8 to SMG1 N-terminus induces a large conformational change in the SMG1 C-terminal head domain containing the catalytic domain. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Part of a complex composed of SMG1, DHX34 and UPF1; within the complex DHX34 acts as a scaffolding protein to facilitate SMG1 phosphorylation of UPF1 (By similarity). Interacts with PRKCI. Interacts with TELO2 and TTI1. Interacts with RUVBL1 and RUVBL2. Interacts with DHX34 (via C-terminus); the interaction is RNA-independent (By similarity).|||Cytoplasm|||Inhibited by caffeine, LY294002 and wortmannin.|||Nucleus|||Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ (By similarity). http://togogenome.org/gene/10090:Fez1 ^@ http://purl.uniprot.org/uniprot/Q8K0X8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the zygin family.|||Cell membrane|||Homodimer. Interacts with the NH2-terminal variable region (V1) of PKC zeta and weakly with that of PKC epsilon. Interacts with UBE4B and SAP30L (By similarity). Interacts with SCOC and ULK1; SCOC interferes with ULK1-binding to FEZ1 (By similarity). Directly interacts with SCOC and UVRAG. Stabilizes the interaction between SCOC and UVRAG during amino acid starvation (By similarity).|||May be involved in axonal outgrowth as component of the network of molecules that regulate cellular morphology and axon guidance machinery. May participate in the transport of mitochondria and other cargos along microtubules (By similarity).|||Phosphorylated by protein kinase C zeta; which enhances interaction with UBE4B and polyubiquitination.|||Polyubiquitinated in a UBE4B-dependent manner; which does not lead to proteasomal degradation and may be important for neurogenic activity. Polyubiquitin linkage seems to be mainly through Lys-26 (By similarity).|||centrosome http://togogenome.org/gene/10090:Vmn1r88 ^@ http://purl.uniprot.org/uniprot/E9Q235 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Inka2 ^@ http://purl.uniprot.org/uniprot/Q80VY2 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the INKA family.|||During development, expressed in oligodendrocyte progenitor cells and in the proliferative neuronal progenitors in the developing cerebellum. In the embryonic brain, not expressed in immature newborn neurons, except for the cells residing in the marginal zone of the embryonic telencephalon. As brain development proceeds during the postnatal stage, expressed in some populations of immature neurons, including the neocortical pyramidal neurons, hippocampal pyramidal neurons and granule cells migrating in the cerebellar cortex. In the adult brain, expression is confined in terminally differentiated neurons in the restricted forebrain regions.|||Enriched in the nervous system.|||Inhibitor of the serine/threonine-protein kinase PAK4. Acts by binding PAK4 in a substrate-like manner, inhibiting the protein kinase activity.|||Interacts with PAK4.|||Nucleus|||The Inka box (also named iBox or inca box) binds and inhibits PAK4 by binding a substrate-like manner. http://togogenome.org/gene/10090:Hpcal1 ^@ http://purl.uniprot.org/uniprot/P62748 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the recoverin family.|||May be involved in the calcium-dependent regulation of rhodopsin phosphorylation.|||Membrane|||Probably binds two or three calcium ions. http://togogenome.org/gene/10090:Tmem198 ^@ http://purl.uniprot.org/uniprot/Q8BG75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM198 family.|||Cell membrane|||Cytoplasmic vesicle|||Interacts with LRP6.|||Membrane|||Promotes LRP6 phosphorylation by casein kinases and thereby plays a role in Wnt signaling. May be a membrane scaffold protein involved in the self-aggregation of LRP6 to further enhance its activity (By similarity). http://togogenome.org/gene/10090:Slc17a7 ^@ http://purl.uniprot.org/uniprot/Q3TXX4 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.|||Cell membrane|||Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-). The allosteric activation by H(+) efficiently prevents non-vesicular efflux across the plasma membrane, thereby restricting L-glutamate transport activity to acidic membranes such as synaptic vesicles.|||Expressed in hippocampus (at protein level). Expressed in the molecular layer of the cerebellum and in retina.|||Expression in brain increases progressively from four days to adulthood.|||Interacts with SHANK3.|||Martineau M. et al. show that may function as a L-glutamate/H(+) antiporter (PubMed:29273736). However, according to Eriksen J. et al., H(+) is an allosteric activator (By similarity).|||Mice begin to die 3 weeks after birth. They exhibit a progressive neurological phenotype including blindness, loss of coordination and enhanced startle response. Glutamatergic neurotransmission is drastically reduced due to a decrease in the reserve pool of synaptic vesicles and reduced quantal size. Visual signaling from photoreceptors to retinal output neurons is impaired while photoentrainment and pupillary light responses remain intact.|||Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, proton, potassium, sodium and phosphate (PubMed:29642010, PubMed:25433636, PubMed:33440152, PubMed:29273736). At the synaptic vesicle membrane, mainly functions as an uniporter which transports preferentially L-glutamate but also phosphate from the cytoplasm into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells (PubMed:25433636, PubMed:29642010, PubMed:15103023, PubMed:15118123). The L-glutamate or phosphate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (PubMed:29642010). In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification (PubMed:25433636, PubMed:29273736, PubMed:29642010). Moreover, may function as a K(+)/H(+) antiport allowing to maintain the electrical gradient and to decrease chemical gradient and therefore sustain vesicular glutamate uptake (By similarity). The vesicular K(+)/H(+) antiport activity is electroneutral (By similarity). At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation (PubMed:33440152, PubMed:29642010). The symporter activity is driven by an inside negative membrane potential and is electrogenic (PubMed:29642010). Is necessary for synaptic signaling of visual-evoked responses from photoreceptors (PubMed:17611277).|||Oscillates diurnally in synaptic vesicles (at protein level).|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Fgfr3 ^@ http://purl.uniprot.org/uniprot/E9QNJ9|||http://purl.uniprot.org/uniprot/F6TK14|||http://purl.uniprot.org/uniprot/Q61563|||http://purl.uniprot.org/uniprot/Q7TSI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Alkbh2 ^@ http://purl.uniprot.org/uniprot/Q6P6J4 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by magnesium ions.|||Belongs to the alkB family.|||Binds 1 Fe(2+) ion per subunit.|||Detected in liver, testis and kidney (at protein level). Detected in heart and testis.|||Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA (PubMed:16174769, PubMed:16642038, PubMed:18519673). Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis (PubMed:16174769, PubMed:16642038, PubMed:18519673) (By similarity). Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine (By similarity). Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription (By similarity). In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (By similarity).|||Interacts with PCNA homotrimer; this interaction is enhanced during the S-phase of the cell cycle. Interacts with nucleolar proteins NCL, UBTF and NPM1. Interacts with XRCC5-XRCC6 heterodimer.|||No visible phenotype, and no effect on the level of 1-ethenoadenine in genomic DNA in aging mice. In contrast, the levels of 1-methyladenine in genomic DNA increase over time in aging adults.|||Nucleus|||The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif, APIM), mediates the colocalization of ALKBH2 with PCNA at the replication foci, coordinating the repair of alkylated DNA damage with DNA replication.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Ddit4 ^@ http://purl.uniprot.org/uniprot/B7ZNP9|||http://purl.uniprot.org/uniprot/Q9D3F7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DDIT4 family.|||By dexamethasone, heat-shock or osmotic stress. Up-regulated by hypoxia, in a HIF1A-dependent but TP53-independent mechanism. Up-regulated upon energy stress. Up-regulated in brain from MPTP-intoxicated mice, a model for Parkinson disease (at protein level). Up-regulated by hypoxia in bowel, liver, spleen, heart, lung, brain and kidney.|||Expressed at 7 dpc. At 11 dpc, expressed in the apical ectodermal ridge. At 13.5 dpc, expressed in the whisker pad, eyelid, breast primordia and developing limb. At 14.5 dpc, expressed in supraorbital and suborbital follicles, whisker pad, limbs and patches of developing epidermis.|||Mitochondrion|||Monomer. Interacts with BTRC. Identified in a complex with CUL4A, DDB1 and BTRC. Interacts with TXNIP; this inhibits the proteasomal degradation of DDIT4 (By similarity).|||No visible phenotype. Mice are normal and less sensitive to oxygen-induced retinopathy. Mitochondria show increased production of reactive oxygen species. Newborn mice show increased radiation-induced apoptosis in brain and thymus, due to increased levels of TP53 and increased TP53 activity. Likewise, cultured embryonic fibroblasts are highly sensitive to DNA damage caused by UV irradiation or doxomycin and display increased levels of TP53 and increased TP53 activity, leading to increased apoptosis. Cultured embryonic fibroblasts are more susceptible to cell death caused by influenza virus infection and produce about 200 times more virus particles than wild-type.|||Phosphorylated by GSK3B; this promotes proteasomal degradation.|||Polyubiquitinated by a DCX (DDB1-CUL4A-RBX1) E3 ubiquitin-protein ligase complex with BTRC as substrate-recognition component, leading to its proteasomal degradation.|||Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves DDIT4/REDD1, AKT1, the TSC1-TSC2 complex and the GTPase RHEB. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage. Regulates p53/TP53-mediated apoptosis in response to DNA damage via its effect on mTORC1 activity. Its role in the response to hypoxia depends on the cell type; it mediates mTORC1 inhibition in fibroblasts and thymocytes, but not in hepatocytes. Inhibits neuronal differentiation and neurite outgrowth mediated by NGF via its effect on mTORC1 activity. Required for normal neuron migration during embryonic brain development. Plays a role in neuronal cell death. Required for mTORC1-mediated defense against viral protein synthesis and virus replication.|||Ubiquitously expressed.|||cytosol http://togogenome.org/gene/10090:1700123O20Rik ^@ http://purl.uniprot.org/uniprot/Q9JJ93 ^@ Subcellular Location Annotation ^@ Mitochondrion http://togogenome.org/gene/10090:Krtap27-1 ^@ http://purl.uniprot.org/uniprot/E9PX37 ^@ Function|||Similarity|||Subunit ^@ Belongs to the PMG family.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Ankrd34a ^@ http://purl.uniprot.org/uniprot/B2RW11|||http://purl.uniprot.org/uniprot/Q7TST1 ^@ Similarity ^@ Belongs to the ANKRD34 family. http://togogenome.org/gene/10090:Or2k2 ^@ http://purl.uniprot.org/uniprot/A2AM35 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ehmt1 ^@ http://purl.uniprot.org/uniprot/Q5DW34 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Chromosome|||Embryos die around E9.5. Levels of H3K9me1 and H3K9me2 are drastically reduced.|||Expressed in the developing limb bud at 11.5 dpc (at protein level).|||Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. During G0 phase, it probably contributes to silencing of MYC- and E2F-responsive genes, suggesting a role in G0/G1 transition in cell cycle. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with probable chromatin reader Baz2b (PubMed:32103178).|||In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.|||Interacts with WIZ. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EHMT1, RING1, RNF2, MBLR, L3MBTL2 and YAF2. Interacts with MPHOSPH8 (By similarity). Interacts with CDYL. Interacts with REST only in the presence of CDYL. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (By similarity). Heterodimer; heterodimerizes with EHMT2. Interacts (via ANK repeats) with RELA (when monomethylated at 'Lys-310'). Interacts with Baz2b (PubMed:32103178). Interacts with MSX1 (PubMed:22629437).|||Methyltransferase activity is inhibited by BIX-01294. Efficiently inhibited by compound E72, a BIX-01294 derivative in which the diazepane ring and the benzyl are replaced with a 3-dimethylaminopropyl and a 5-aminopentyl group at sites B and C, respectively (By similarity).|||Nucleus|||The ANK repeats specifically recognize and bind H3K9me1 and H3K9me2 (By similarity). They also specifically recognize and bind RELA subunit of NF-kappa-B, when RELA is monomethylated at 'Lys-310'.|||The SET domain mediates interaction with WIZ.|||Ubiquitous. http://togogenome.org/gene/10090:Defb7 ^@ http://purl.uniprot.org/uniprot/Q91V70 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family. LAP/TAP subfamily.|||Has bactericidal activity.|||Secreted http://togogenome.org/gene/10090:Dstn ^@ http://purl.uniprot.org/uniprot/Q4FK36|||http://purl.uniprot.org/uniprot/Q9R0P5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Tissue Specificity ^@ Actin-depolymerizing protein. Severs actin filaments (F-actin) and binds to actin monomers (G-actin). Acts in a pH-independent manner.|||Belongs to the actin-binding proteins ADF family.|||ISGylated.|||In 10.5 dpc embryo somites is expressed in a superficial patch of cells (adaxial region).|||Widely expressed. Not found in skeletal muscle. http://togogenome.org/gene/10090:Tmem54 ^@ http://purl.uniprot.org/uniprot/A2A7R1|||http://purl.uniprot.org/uniprot/A2A7R2|||http://purl.uniprot.org/uniprot/Q9D6Y3|||http://purl.uniprot.org/uniprot/Q9D7S1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM54 family.|||Membrane http://togogenome.org/gene/10090:Or13f5 ^@ http://purl.uniprot.org/uniprot/Q7TS18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gsdme ^@ http://purl.uniprot.org/uniprot/Q9Z2D3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the gasdermin family.|||Cell membrane|||Cleavage at Asp-270 by CASP3 (mature and uncleaved precursor forms) or granzyme B (GZMB) relieves autoinhibition and is sufficient to initiate pyroptosis.|||Expressed in spleen, kidney, large and small intestine, testicle, stomach and by CD4(+)CD(8+) T cells in thymus (PubMed:28459430). Expressed by macrophages (PubMed:28045099).|||Homooligomer; homooligomeric ring-shaped pore complex containing 27-28 subunits when inserted in the membrane.|||Intramolecular interactions between N- and C-terminal domains may be important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain, that is released upon cleavage by CASP3 or granzyme B (GZMB).|||Mutant mice develop normally, including the immune system. After injection of the chemotherapy drug cisplatin, they look more healthy and vigorous than wild type.|||Pore-forming protein produced by cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis, respectively (PubMed:32188940). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukins (IL1B and IL16) and triggering pyroptosis (PubMed:33852854). Binds to inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (By similarity). Cleavage by CASP3 switches CASP3-mediated apoptosis induced by TNF or danger signals, such as chemotherapy drugs, to pyroptosis (PubMed:32188940). Mediates secondary necrosis downstream of the mitochondrial apoptotic pathway and CASP3 activation as well as in response to viral agents (PubMed:28045099). Exhibits bactericidal activity (By similarity). Cleavage by GZMB promotes tumor suppressor activity by triggering robust anti-tumor immunity (PubMed:32188940). Suppresses tumors by mediating granzyme-mediated pyroptosis in target cells of natural killer (NK) cells: cleavage by granzyme B (GZMB), delivered to target cells from NK-cells, triggers pyroptosis of tumor cells and tumor suppression (By similarity). May play a role in the p53/TP53-regulated cellular response to DNA damage (By similarity).|||Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis. This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-E, N-terminal) binds to membranes and forms pores, triggering pyroptosis.|||Succination by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits processing by caspases, and ability to initiate pyroptosis. Succination modification is catalyzed by a non-enzymatic reaction caused by an accumulation of fumarate.|||The full-length protein before cleavage is inactive: intramolecular interactions between N- and C-terminal domains mediate autoinhibition in the absence of activation signal (By similarity). The intrinsic pyroptosis-inducing activity is carried by the released N-terminal moiety (Gasdermin-E, N-terminal) following cleavage by CASP3 or granzyme B (GZMB) (By similarity). Activated by NLRP1 in the absence of GSDMD expression: NLRP1 cleaves and activates CASP8, promoting downstream activation of CASP3 and subsequent activation of GSDME (PubMed:33852854).|||cytosol http://togogenome.org/gene/10090:Usp17lc ^@ http://purl.uniprot.org/uniprot/G5E8I7 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase C19 family. USP17 subfamily.|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes (PubMed:8995226, PubMed:11443643). Important for preimplantation stage embryonic development (PubMed:22984479).|||Embryonic lethal, with no survival beyond embryonic stage E5.5. Blastocysts fail to hatch and there is significant apoptosis of the trophectoderm. Cell proliferation may also be impaired. Blastocysts at stage E3.5 appear to have normal morphology.|||Endoplasmic reticulum|||Expressed in T cells.|||Nucleus|||Rapidly up-regulated in response to the cytokine IL2. http://togogenome.org/gene/10090:Slitrk6 ^@ http://purl.uniprot.org/uniprot/Q8C110 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SLITRK family.|||Cell membrane|||During inner ear development, detected early in the otic vesicle, and later in cochlear and vestibular sensory epithelia. Present in the presumptive organ of Corti by 14.5 dpc, and then confined to the supporting cell types at later stages of embryonic development and at the newborn. In the vestibular sensory epithelia, present at the lumenal surface. However, it is detected in the non-hair cell region, presumably in the lumenal processes of the supporting cells. Transiently expressed in the spiral and vestibular ganglion neurons (at protein level) (PubMed:19936227). First expressed at 8.5 dpc. In the newborn, broadly detected in neural retina. Later, in P10 retina, expression is enhanced in the inner nuclear and outer plexiform layers. Expression in retina decreases as development proceeded, and is detected in the inner nuclear layer and in a subset of cells in the ganglion cell layer of adults (PubMed:23543054).|||In the embryo, expressed in otic cyst, lateral trunk epidermis and underlying mesodermal tissue, limb bud, maxillary process, cochlea, retina, tongue, tooth primordium, central nervous system, and primordia of visceral organs including lung, gastrointestinal tract and pancreas. In the central nervous system, expressed primarily in dorsal thalamus, cerebellum and medulla.|||Male and female mice grow without showing any external abnormalities and are fertile but display auditory deficits. In the developing inner ear, mice show pronounced reduction of cochlear innervation, despite normal gross morphology and general organization of the organ of Corti (PubMed:19936227). Adult mice have reduced startle response and impaired auditory brainstem responses consistent with mid-frequency range hearing loss (PubMed:21298075). Retinas in postnatal development display a delay in synaptogenesis (PubMed:23543054).|||Regulator of neurite outgrowth required for normal hearing and vision. http://togogenome.org/gene/10090:Hint3 ^@ http://purl.uniprot.org/uniprot/Q9CPS6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the HINT family.|||Cytoplasm|||Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By similarity). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase (By similarity).|||Forms dimers to octamers and even larger oligomer (By similarity). Interacts with CALM1 (PubMed:31088288).|||Nucleus http://togogenome.org/gene/10090:Msl1 ^@ http://purl.uniprot.org/uniprot/Q6PDM1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the msl-1 family.|||Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the KAT8/MOF/MYST1, MSL1/hampin, MSL2 and MSL3 (By similarity). Directly interacts with MSL2 via its coiled coil domain (By similarity). Directly interacts with NUPR1 (By similarity). Interacts with TP53BP1; this interaction may be required for MSL1 DNA repair activity, but not for histone acetyltransferase activity (By similarity). Forms a MSL heterotetrameric core with MSL2 (By similarity). Interacts with KAT8 and MSL3; both interactions are direct (PubMed:21217699, PubMed:17335777). Isoform 1 and isoform 3 interact with TTC4 (PubMed:17335777). Isoform 1 interacts with ECM2 and PIHD1 (PubMed:17335777).|||Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at 'Lys-16' (H4K16ac) which is implicated in the formation of higher-order chromatin structure (PubMed:24913909). Greatly enhances MSL2 E3 ubiquitin ligase activity, promoting monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub) (By similarity). This modification in turn stimulates histone H3 methylation at 'Lys-5' (H3K4me) and 'Lys-80' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (By similarity). In the MSL complex, acts as a scaffold to tether MSL3 and KAT8 together for enzymatic activity regulation (PubMed:21217699). Isoform 2, isoform 3, isoform 4 and isoform 5 can medite histone H4 acetylation at 'Lys-16' (H4K16ac) (PubMed:24913909).|||Isoform 3 and isoform 5 are testis-specific (PubMed:16119455). Isoform 1 and isoform 4 are ubiquitously expressed (PubMed:16119455). Isoform 2 is expressed at low levels in the testis and brain (PubMed:16119455).|||Nucleus|||Nucleus speckle|||Sumoylated with SUMO1.|||The coiled coil is formed by helices from two subunits in the MSL1 homodimer.|||nucleoplasm http://togogenome.org/gene/10090:Or2v2 ^@ http://purl.uniprot.org/uniprot/Q7TQS8|||http://purl.uniprot.org/uniprot/Q8VEY7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dip2a ^@ http://purl.uniprot.org/uniprot/F8WI56|||http://purl.uniprot.org/uniprot/Q8BWT5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DIP2 family.|||Catalyzes the de novo synthesis of acetyl-CoA in vitro (PubMed:30672040). Promotes acetylation of CTTN, possibly by providing the acetyl donor, ensuring correct dendritic spine morphology and synaptic transmission (PubMed:31600191). Binds to follistatin-related protein FSTL1 and may act as a cell surface receptor for FSTL1, contributing to AKT activation and subsequent FSTL1-induced survival and function of endothelial cells and cardiac myocytes (By similarity).|||Cell membrane|||Defects in dendritic spine morphogenesis along with thin postsynaptic density and reduced synaptic transmission of pyramidal neurons (PubMed:31600191). Reduced postsynaptic density protein levels of Grin1/Nmdar1, Grin2a/NR2A, Grin2b/NR2B and Gria1/GluR1 (PubMed:31600191). Significantly reduced acetylation of Cttn (PubMed:31600191). Autism-like behaviors including excessive repetitive self-grooming, reduced vocalization time and impaired social interaction (PubMed:31600191).|||Detected in heart, liver, spleen, lung, kidney and brain with highest levels in brain (at protein level) (PubMed:30672040). In adult cortex, preferentially expressed in excitatory neurons (PubMed:31600191). Broadly expressed in neuronal, reproductive and vascular tissues as well as in heart, kidney, liver and lung with expression detected in neurons, mesenchyme, endothelium, smooth muscle cells and cardiomyocytes (PubMed:26605542). Expressed in ectoderm-derived tissues in the developing embryo (PubMed:26605542). Expressed in the developing nervous system (PubMed:12137943).|||In brain, expressed from embryo to adult with a constant increase during postnatal development in the cerebral cortex (at protein level) (PubMed:31600191). Expressed at all stages of embryonic development, including 7 dpc, 11 dpc, 15 dpc and 17 dpc (PubMed:12137943). Higher level of expression is seen at later stages of embryonic development (PubMed:12137943). In 9.5 dpc embryos, expression is diffusely distributed in the regions of the brain, optic vesicles, otic vesicles, cervical and upper thoracic segments of the spinal cord (PubMed:12137943). The expression is more intense in the dorsal portions of the central nervous system (CNS) (PubMed:12137943). In the brain, expression is localized in prosencephalon, mesencephalon and rhombencephalon (PubMed:12137943). In 10.5 embryos, expression area is more restricted, but still within the CNS and the sense organs. The spinal cord expression disappears (PubMed:12137943).|||Interacts with FSTL1; DIP2A may act as a cell surface receptor for FSTL1 (PubMed:20054002). Interacts (via N-terminus) with CTTN (via SH3 domain); the interaction promotes acetylation of CTTN and is required for proper synaptic transmission (PubMed:31600191). Interacts with SHANK3 (PubMed:31600191).|||Mitochondrion|||dendritic spine http://togogenome.org/gene/10090:Pgrmc1 ^@ http://purl.uniprot.org/uniprot/O55022 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome b5 family. MAPR subfamily.|||Component of a progesterone-binding protein complex. Binds progesterone. Has many reported cellular functions (heme homeostasis, interaction with CYPs). Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan (PubMed:28005395). Intracellular heme chaperone. Regulates heme synthesis via interactions with FECH and acts as a heme donor for at least some hemoproteins (PubMed:27599036).|||Double conditional knockout for PGRMC1 and PGRMC2 from female reproductive tissues results in postimplantation embryonic death leading to subfertility, with female mice producing fewer pups/litter than wild-types. They undergo premature reproductive senescence, producing fewer litters overall during the trial compared with wild-types.|||Endoplasmic reticulum membrane|||Homodimer. Forms stable homodimer through hydrophobic heme-heme stacking interactions. Interacts with PGRMC2 (PubMed:31748741). Interacts with FECH; the interaction results in decreased FECH activity (PubMed:27599036). Interacts with EGFR, CYP1A1 and CYP3A4; the interactions require PGRMC1 homodimerization (By similarity).|||Microsome membrane|||Mitochondrion outer membrane|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||O-glycosylated; contains chondroitin sulfate attached to Ser-54. Ser-54 is in the cytoplasmic domain but the glycosylated form was detected in urine, suggesting that the membrane-bound form is cleaved, allowing for production of a secreted form which is glycosylated.|||Secreted|||The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 107 and 131. http://togogenome.org/gene/10090:Gm21257 ^@ http://purl.uniprot.org/uniprot/Q62459 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Apela ^@ http://purl.uniprot.org/uniprot/P0DMC4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Elabela/Toddler family.|||Endogenous ligand for the apelin receptor (APLNR) (By similarity). Hormone required for mesendodermal differentiation, blood vessels formation and heart morphogenesis during early development and for adult cardiovascular homeostasis (PubMed:28371822, PubMed:28854362, PubMed:28890073, PubMed:28663440). Drives internalization of the APLNR (By similarity). Acts as a motogen by promoting mesendodermal cell migration during gastrulation by binding and activating APLNR (By similarity). Acts as an early embryonic regulator of cellular movement with a role in migration and development of cardiac progenitor cells (PubMed:28854362). May act as a chemoattractant for the activation of angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Positively regulates sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel sprouting (PubMed:28890073). Plays a role in placental vascular development; promotes placental trophoblast invasion and spiral artery remodeling in the uterus (PubMed:28663440). Involved in the regulation of maternal cardiovascular homeostasis to prevent gestational hypertension and for potent cardioprotective functions during heart failure (PubMed:28371822, PubMed:28663440). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity).|||Expressed during early embryonic development from the two cell to blastocyst stages (PubMed:28663440). Expressed in populations of the definitive endoderm from 7 to 8.5 dpc (PubMed:20153842).|||Expressed in the placenta (PubMed:28663440). Expressed in syncytiotrophoblasts of the placenta labyrinth at 10.5 dpc (PubMed:28663440). Expressed in placental chorionic trophoblasts (at protein level) (PubMed:28663440). Expressed in a small population of epiblast cells in the distal half of the embryo at 7 dpc (PubMed:20153842, PubMed:28854362). Expressed in newly formed definitive endoderm cells in the proximal half of the embryo, while it is not present in extra-embryonic endoderm at 7.5 dpc (PubMed:20153842, PubMed:28854362). This expression pattern then changes to the ventral aspect of the developing foregut pocket and the entire hindgut pocket at 8.5 dpc, before becoming restricted to the foregut overlying the heart and the posterior-most hindgut (PubMed:20153842). Not detected in endothelial precursor cells of the yolk sac at 8 dpc (PubMed:28663440). Expressed in extraembryonic tissues as well as in the chorion at 8.25 dpc (PubMed:28854362). Expressed in endometrial stroma of the uterus of pregnant mice at 8.5 dpc (PubMed:28663440). Expressed in the developing heart, caudal neural tube and trophobasts at 9 dpc (PubMed:28663440). Expressed in the chorionic plate of the chorioallantoic placenta at 9 dpc (PubMed:28663440). Expressed in the posterior half of the ventral neural tube at 9.25 dpc (PubMed:20153842). Expressed in trophoblast cells at the periphery of the placenta at 9.5 dpc (PubMed:28854362). Expressed in collecting ducts of the kidney of pregnant mice at 10.5 dpc (PubMed:28663440). Expressed in the epicardium of the developing heart at 11.5 dpc (PubMed:26611206, PubMed:28890073). Expressed weakly in the adult heart (PubMed:26611206). Expressed in endothelial cells and fibroblasts and weakly in cardiomyocytes (PubMed:26611206).|||Interacts with APLNR.|||Mice lacking APELA are not represented at the expected Mendelian ratios (PubMed:28854362, PubMed:28663440). Mutant embryos exhibit around 10% to 50% incidence of incomplete penetrance of embryonic lethality (PubMed:28854362, PubMed:28663440). Fetal death is increased especially in mothers devoid of all Apela expression (PubMed:28663440). Mutant embryos show extraembryonic tissues anomalies, such as ectopic anterior chorion, mesoderm yolk sac and blood island protrusions and reduced allantois thickness at 8.25 dpc (PubMed:28854362). Mutant embryos show improper establishment of the fetal-maternal circulation, such as underdeveloped yolk sac vasculature, embryonic vascular malformations and impaired cardiac tube looping at 9.5 and 10.5 dpc (PubMed:28854362, PubMed:28663440). Show also defect in somitic vasculature at 10.5 dpc. The heart of mutant embryos show reduced coronary vessel growth at 13.5 dpc and 15.5 dpc (PubMed:28890073). The placenta of mutant pregnant mice show decreased labyrinth thickness, poor vasculature and decreased cell proliferation (PubMed:28663440). Mutant pregnant mice that survived to adulthood developed preeclampsia, including increased systolic blood pressure, proteinuria, and glomerular endotheliosis (PubMed:28663440). Mutant embryos show altered expression of several erythroid and myeloid progenitor genes at 7.5 dpc (PubMed:28854362). Mutant embryos show increased expression of hypoxia-related genes in the placenta at 10.5 (PubMed:28663440). Double knockout mice of APELA and APLN genes exhibit the same penetrance, embryonic lethality and cardiovascular malformations as single APELA knockout mice (PubMed:28854362).|||Secreted|||Up-regulated following myocardial infarction (MI) (at protein level) (PubMed:26611206).|||extracellular space http://togogenome.org/gene/10090:B3gnt9 ^@ http://purl.uniprot.org/uniprot/Q8VI16 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 31 family.|||Golgi apparatus membrane http://togogenome.org/gene/10090:Cpne1 ^@ http://purl.uniprot.org/uniprot/Q3U893|||http://purl.uniprot.org/uniprot/Q8C166 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the copine family.|||C2 domains are necessary for calcium-dependent cell membrane association. C2 domains are necessary for neuronal progenitor cell differentiation in a calcium-independent manner.|||Calcium-dependent phospholipid-binding protein that plays a role in calcium-mediated intracellular processes. Involved in the TNF-alpha receptor signaling pathway in a calcium-dependent manner. Exhibits calcium-dependent phospholipid binding properties. Plays a role in neuronal progenitor cell differentiation; induces neurite outgrowth via a AKT-dependent signaling cascade and calcium-independent manner. May recruit target proteins to the cell membrane in a calcium-dependent manner. May function in membrane trafficking. Involved in TNF-alpha-induced NF-kappa-B transcriptional repression by inducing endoprotease processing of the transcription factor NF-kappa-B p65/RELA subunit. Also induces endoprotease processing of NF-kappa-B p50/NFKB1, p52/NFKB2, RELB and REL.|||Cell membrane|||Cytoplasm|||Homodimer; homodimerizes via its C2 domains. Interacts with p65/RELA (via N-terminus); this interaction induces proteolytic cleavage of p65/RELA subunit and inhibition of NF-kappa-B transcriptional activity. Interacts (via VWFA domain) with ACTB, CCDC22, MYCBP2, PPP5C, RDX and UBE2O.|||Nucleus http://togogenome.org/gene/10090:Krtap5-1 ^@ http://purl.uniprot.org/uniprot/Q64507 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the KRTAP type 5 family.|||Expressed during the active phases of the hair cycle in the medulla and the inner root sheath of the forming hair. Also expressed in the upper layers of the epidermis of skin.|||In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.|||Interacts with hair keratins. http://togogenome.org/gene/10090:Or5p50 ^@ http://purl.uniprot.org/uniprot/Q8VF66 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Fgd6 ^@ http://purl.uniprot.org/uniprot/Q69ZL1 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||May activate CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. May play a role in regulating the actin cytoskeleton and cell shape (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Nup50 ^@ http://purl.uniprot.org/uniprot/Q9JIH2 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the nuclear pore complex that has a direct role in nuclear protein import (PubMed:10811608). Actively displaces NLSs from importin-alpha, and facilitates disassembly of the importin-alpha:beta-cargo complex and importin recycling (PubMed:16222336). Interacts with regulatory proteins of cell cycle progression including CDKN1B (PubMed:10891500, PubMed:10811608). This interaction is required for correct intracellular transport and degradation of CDKN1B (PubMed:10811608).|||Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited.|||Does not interact with TPR (By similarity). Interacts with Importin alpha-2, Importin beta, Importin beta-2, NUP153, Ran binding protein 7, CDKN1B and itself.|||NUP50 targeted disruption results in a complex phenotype characterized by neural tube defects, exencephaly, intrauterine growth retardation, and late embryonic lethality.|||Nucleus membrane|||Widely expressed at low levels. Highest in the developing neural tube and adult testes.|||nuclear pore complex http://togogenome.org/gene/10090:Snx4 ^@ http://purl.uniprot.org/uniprot/Q91YJ2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Early endosome|||Early endosome membrane|||Heterodimer; heterodimerizes with SNX7 or SNX30 (By similarity). Interacts with WWC1/KIBRA (By similarity). Identified in a complex with WWC1/KIBRA and dynein components DYNLL1 and DYNC1I2 (By similarity). Interacts with BIN1 (PubMed:12668730).|||Involved in the regulation of endocytosis and in several stages of intracellular trafficking. Plays a role in recycling endocytosed transferrin receptor and prevent its degradation. Involved in autophagosome assembly by regulating trafficking and recycling of phospholipid scramblase ATG9A.|||The PX domain binds phosphatidylinositol 3-phosphate which is necessary for peripheral membrane localization. http://togogenome.org/gene/10090:Ints3 ^@ http://purl.uniprot.org/uniprot/Q7TPD0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 3 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1. Interacts with SOSS-B1/NABP2, SOSS-B2/NABP1 and SOSS-C/INIP; the interaction is direct. Interacts with NBN/NBS1.|||Component of the Integrator (INT) complex. The Integrator complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex.|||Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. The SOSS complex is required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. In the SOSS complex, it is required for the assembly of the complex and for stabilization of the complex at DNA damage sites.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Dchs1 ^@ http://purl.uniprot.org/uniprot/E9PVD3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, acting in the regulation of cell migration involved in valve formation (PubMed:26258302).|||Cell membrane|||Deficient mice exhibit postnatal lethality, growth retardation, small lungs, abnormal cochlea morphology, abnormal kidney morphology, cardiovascular abnormalities and skeletal abnormalities. DCHS1 and FAT4 single mutants and DCHS1/FAT4 double mutants have similar phenotypes. Heterozygous mice lacking one DCHS1 allele exhibit mitral valve prolapse with posterior leaflet elongation, leaflet thickening, and myxomatous degeneration with increased proteoglycan accumulation in both mitral leaflets (PubMed:26258302).|||Expressed in all layers of the developing brain, with expression being most prominent at the ventricular margin. Expressed throughout cardiac development in the endothelial cells and interstitial cells of the developing valves (at protein level). Expression is observed in the endocardium and mesenchyme of the superior and inferior cushions at day 11.5 dpc. At days 13.5 dpc and 15.5 dpc, expression is observed in the forming anterior and posterior mitral leaflets (PubMed:26258302).|||Expressed in the epicardium and atrioventricular sulcus (at protein level).|||Heterophilic interaction with FAT4; this interaction affects their respective protein levels. http://togogenome.org/gene/10090:Pde1a ^@ http://purl.uniprot.org/uniprot/Q61481 ^@ Activity Regulation|||Cofactor|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by the binding of calmodulin in the presence of Ca(2+).|||Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.|||Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.|||Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.|||Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP.|||Expressed in brain, kidney and testis.|||Homodimer (By similarity). Interacts with YWHAZ (By similarity).|||Probable cloning artifact.|||Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+).|||flagellum http://togogenome.org/gene/10090:Nfe2l3 ^@ http://purl.uniprot.org/uniprot/Q3UZC1|||http://purl.uniprot.org/uniprot/Q9WTM4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates erythroid-specific, globin gene expression.|||Belongs to the bZIP family. CNC subfamily.|||Heterodimer with MAFG, MAFK and other small MAF proteins that binds to the MAF recognition elements (MARE).|||High level expression in brain, thymus, testis and placenta. Medium level expression in uterus, stomach and lung. Low level expression in kidney. No expression in heart, liver, spleen and ovary.|||Nucleus http://togogenome.org/gene/10090:Il10ra ^@ http://purl.uniprot.org/uniprot/Q61727 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type II cytokine receptor family.|||Cell membrane|||Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a conformational change in IL10RB, allowing IL10RB to bind IL10 as well. In turn, the heterotetrameric assembly complex, composed of two subunits of IL10RA and IL10RB, activates the kinases JAK1 and TYK2 that are constitutively associated with IL10RA and IL10RB respectively. These kinases then phosphorylate specific tyrosine residues in the intracellular domain in IL10RA leading to the recruitment and subsequent phosphorylation of STAT3 (PubMed:8910398). Once phosphorylated, STAT3 homodimerizes, translocates to the nucleus and activates the expression of anti-inflammatory genes. In addition, IL10RA-mediated activation of STAT3 inhibits starvation-induced autophagy (By similarity).|||Cytoplasm|||Interacts with IL10. Interacts with IL10RB. Interacts (via its cytoplasmic domain) with JAK1 (via N-terminus). Interacts with BTRC; this interaction leads to IL10RA ubiquitination and subsequent degradation (By similarity). Interacts with STAT3 (PubMed:8910398).|||Phosphorylated. Phosphorylation of the cytoplasmic tail induced STAT3 activation.|||Ubiquitinated by BTRC; ubiquitination leads to endocytosis and subsequent degradation of IL10RA. http://togogenome.org/gene/10090:Cep41 ^@ http://purl.uniprot.org/uniprot/Q99NF3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 10-13 dpc, embryos show a range of phenotypes, such as malformed hindbrain, exencephaly, brain hemorrhage, dilated pericardial sac and lethality. For an unclear reason, some homozygous mutants develop normally, suggesting presence of extragenic phenotypic modifiers.|||Belongs to the CEP41 family.|||Found in a complex with TTLL6.|||Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of TTLL6, a tubulin polyglutamylase, between the basal body and the cilium.|||centrosome|||cilium|||cilium basal body http://togogenome.org/gene/10090:Mettl13 ^@ http://purl.uniprot.org/uniprot/Q91YR5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily.|||Cytoplasm|||Dual methyltransferase that catalyzes methylation of elongation factor 1-alpha (EEF1A1 and EEF1A2) at two different positions, and is therefore involved in the regulation of mRNA translation (By similarity). Via its C-terminus, methylates EEF1A1 and EEF1A2 at the N-terminal residue 'Gly-2' (By similarity). Via its N-terminus dimethylates EEF1A1 and EEF1A2 at residue 'Lys-55' (By similarity). Has no activity towards core histones H2A, H2B, H3 and H4 (By similarity). Negatively regulates cell proliferation at G1/S transition via transcriptional suppression of cell cycle regulatory genes such as CDK4 and CDK6 (By similarity).|||Expressed in the inner ear (at protein level) (PubMed:29408807). Expression is detected in the cochlear duct, spiral limbus region, efferent and afferent nerves, and in spiral ganglion neurons (at protein level) (PubMed:29408807).|||Forms a tripartite complex containing GAB1, METTL13 and SPRY2 (By similarity). Within the complex interacts with GAB1 and SPRY2 (By similarity).|||Mitochondrion|||Nucleus http://togogenome.org/gene/10090:B4galt6 ^@ http://purl.uniprot.org/uniprot/Q3UUA9|||http://purl.uniprot.org/uniprot/Q9WVK5 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 7 family.|||Brain and kidney.|||Catalyzes the synthesis of lactosylceramide (LacCer) via the transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) (PubMed:23882130, PubMed:30114188). LacCer is the starting point in the biosynthesis of all gangliosides (membrane-bound glycosphingolipids) which play pivotal roles in the CNS including neuronal maturation and axonal and myelin formation (PubMed:30114188).|||Golgi apparatus membrane|||Golgi stack membrane|||Inhibited by EDTA.|||Membrane|||Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.|||Single knockout mice are born normally and grow to adulthood without apparent abnormalities (PubMed:23882130). Decreased glucosylceramide beta-1,4-galactosyltransferase activity seen in the brain of female mice whereas minimal or no reduction in the enzyme activity seen in the male brain (PubMed:23882130). Double knockout mice of B4GALT5 and B4GALT6 genes develop normally during embryogenesis and perinatal stage (PubMed:30114188). However, they show growth retardation and motor deficits with hindlimb dysfunction at 2 weeks of age, and they all die by 4 weeks of age (PubMed:30114188). Axonal and myelin formation are remarkably impaired in the spinal cords and increased immature neurons in the cerebral cortices seen (PubMed:30114188). Glucosylceramide beta-1,4-galactosyltransferase activity and major brain gangliosides are completely absent in the brain (PubMed:30114188). http://togogenome.org/gene/10090:Cks1brt ^@ http://purl.uniprot.org/uniprot/Q3UNC9 ^@ Function|||Similarity|||Subunit ^@ Belongs to the CKS family.|||Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.|||Forms a homohexamer that can probably bind six kinase subunits. http://togogenome.org/gene/10090:6430571L13Rik ^@ http://purl.uniprot.org/uniprot/Q8BGK9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Aup1 ^@ http://purl.uniprot.org/uniprot/I6L970|||http://purl.uniprot.org/uniprot/P70295|||http://purl.uniprot.org/uniprot/Q3TBX5|||http://purl.uniprot.org/uniprot/Q3U3K9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AUP1 family.|||Endoplasmic reticulum membrane|||Identified in a complex that contains SEL1L, OS9, FAF2/UBXD8, UBE2J1/UBC6E and AUP1 (By similarity). Interacts with the cytoplasmic tail of ITGA2B, ITGA1, ITGA2, ITGA5, ITGAV and ITGAM (By similarity). Interacts (via C-terminus) with UBE2G2; the interaction recruits UBE2G2 to lipid droplets (By similarity). Interacts with ubiquitin ligases AMFR/gp78 and RNF139/TRC8; this promotes interaction of UBE2G2 with AMFR and RNF139 (By similarity). Interacts with apolipoprotein APOB (By similarity).|||Lipid droplet|||Membrane|||Monoubiquitinated and diubiquitinated.|||Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome (By similarity). Plays a role in lipid droplet formation (By similarity). Induces lipid droplet clustering (By similarity). Recruits ubiquitin-conjugating enzyme UBE2G2 to lipid droplets which facilitates its interaction with ubiquitin ligases AMFR/gp78 and RNF139/TRC8, leading to sterol-induced ubiquitination of HMGCR and its subsequent proteasomal degradation (By similarity). Also required for the degradation of INSIG1, SREBF1 and SREBF2 (By similarity). Plays a role in regulating assembly and secretion of very low density lipoprotein particles and stability of apolipoprotein APOB (By similarity).|||The CUE domain is required for interaction with the ER quality control machinery and misfolded substrates, ubiquitination, lipid clustering and interaction with AMFR but is not required for localization to lipid droplets.|||Ubiquitous. http://togogenome.org/gene/10090:Hus1 ^@ http://purl.uniprot.org/uniprot/Q8BQY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the HUS1 family.|||Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (By similarity).|||Component of the toroidal 9-1-1 (RAD9-RAD1-HUS1) complex, composed of RAD9A, RAD1 and HUS1. The 9-1-1 complex associates with LIG1, POLB, FEN1, RAD17, HDAC1, RPA1 and RPA2. The 9-1-1 complex associates with the RAD17-RFC complex. HUS1 interacts with POLB, HDAC1, FEN1, PCNA, RAD1, RAD9A and RAD9B. HUS1 does not interact with RAD17. Interacts with DNAJC7 (By similarity).|||Cytoplasm|||Nucleus|||Ubiquitous. http://togogenome.org/gene/10090:Gpr137c ^@ http://purl.uniprot.org/uniprot/A0A2I3BPD5|||http://purl.uniprot.org/uniprot/E9Q343 ^@ Function|||Subcellular Location Annotation ^@ Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.|||Lysosome membrane|||Membrane http://togogenome.org/gene/10090:Wdr55 ^@ http://purl.uniprot.org/uniprot/Q9CX97 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat WDR55 family.|||Cytoplasm|||Death before implantation of the embryo.|||Nucleolar protein that acts as a modulator of rRNA synthesis. Plays a central role during organogenesis.|||nucleolus http://togogenome.org/gene/10090:Or7e168 ^@ http://purl.uniprot.org/uniprot/Q7TRF5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ccl21a ^@ http://purl.uniprot.org/uniprot/P84444 ^@ Disease Annotation|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intercrine beta (chemokine CC) family.|||Binds to CCR7 and to CXCR3.Interacts with PDPN; relocalizes PDPN to the basolateral membrane.|||Expressed strongly in lung, spleen, thymus, peripheral and mesentric lymph nodes. Also expressed in the testis, kidney, liver, and heart.|||Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Potent mesangial cell chemoattractant. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs.|||Mice carrying an autosomal recessive mutation designated paucity of lymph node T-cells (plt) show dramatically reduced numbers of T-cells in lymph nodes, Peyer patches, and the white pulp of the spleen. Plt seems to correspond to Scya21b.|||Secreted|||Three genes code for Ccl21 in mouse. Ccl21b and Ccl21c produce identical proteins while the protein produced by Ccl21a differs at only one position. Ccl21b and Ccl21c have 'Leu-65' (6Ckine-Leu) while Ccl21a has Ser-65 (6Ckine-Ser). http://togogenome.org/gene/10090:Arsi ^@ http://purl.uniprot.org/uniprot/Q32KI9 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Displays arylsulfatase activity at neutral pH, when co-expressed with SUMF1; arylsulfatase activity is measured in the secretion medium of retinal cell line, but no activity is recorded when measured in cell extracts.|||Endoplasmic reticulum|||Secreted|||The oxidation of Cys-93 residue to 3-oxoalanine (also known as C(alpha)-formylglycine) by SUMF1/Sulfatase-modifying factor 1, seems critical for catalytic activity. http://togogenome.org/gene/10090:Msl3 ^@ http://purl.uniprot.org/uniprot/Q9WVG9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the MSL histone acetyltransferase complex at least composed of the KAT8/MOF, MSL1/hampin, MSL2 and MSL3. Interacts (via the MRG domain) with MSL1 and KAT8/MOF (PubMed:21217699).|||Has a role in chromatin remodeling and transcriptional regulation. Has a role in X inactivation. Component of the MSL complex which is responsible for the majority of histone H4 acetylation at 'Lys-16' which is implicated in the formation of higher-order chromatin structure. Specifically recognizes histone H4 monomethylated at 'Lys-20' (H4K20Me1) in a DNA-dependent manner and is proposed to be involved in chromosomal targeting of the MSL complex.|||Nucleus http://togogenome.org/gene/10090:Krt80 ^@ http://purl.uniprot.org/uniprot/Q0VBK2 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively). http://togogenome.org/gene/10090:Ubd ^@ http://purl.uniprot.org/uniprot/P63072 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can be acetylated.|||Cytoplasm|||Interacts directly with the 26S proteasome. The interaction with NUB1 via the N-terminal ubiquitin domain facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates its own degradation and that of its conjugates. Interacts (via ubiquitin-like 1 domain) with the spindle checkpoint protein MAD2L1 during mitosis. Present in aggresomes of proteasome inhibited cells. Interacts with HDAC6 under proteasome impairment conditions (By similarity). Forms a thioester with UBA6 in cells stimulated with tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg) (PubMed:17889673). Interacts with SQSTM1 and TP53/p53 (By similarity).|||Mostly expressed in thymus and intestine.|||Nucleus|||Rapidly degraded by the proteasome. Cell-cycle regulation with highest expression during the S-phase (at protein level). Over expressed in hepatocytes by drug injury (e.g. DDC; diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate). Inducible by the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg).|||Spontaneous sporadic apoptotic death. Higher sensitivity toward endotoxin challenge. Abrogated TNF-alpha-induced NF-kappa-B activation and reduced induction of NF-kappa-B-regulated genes. Impaired TNF-alpha-induced I-kappa-B-alpha degradation and nuclear translocation of p65 in RTECs. Reduced expression of LMP2.|||Ubiquitin-like protein modifier which can be covalently attached to target protein and subsequently leads to their degradation by the 26S proteasome, in a NUB1-dependent manner. Probably functions as a survival factor. Promotes the expression of the proteasome subunit beta type-9 (PSMB9/LMP2). Regulates TNF-alpha-induced and LPS-mediated activation of the central mediator of innate immunity NF-kappa-B by promoting TNF-alpha-mediated proteasomal degradation of ubiquitinated-I-kappa-B-alpha. Required for TNF-alpha-induced p65 nuclear translocation in renal tubular epithelial cells (RTECs). May be involved in dendritic cell (DC) maturation, the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T-cell responses. Mediates mitotic non-disjunction and chromosome instability, in long-term in vitro culture and cancers, by abbreviating mitotic phase and impairing the kinetochore localization of MAD2L1 during the prometaphase stage of the cell cycle. May be involved in the formation of aggresomes when proteasome is saturated or impaired. Mediates apoptosis in a caspase-dependent manner, especially in renal epithelium and tubular cells during renal diseases. http://togogenome.org/gene/10090:Gm21151 ^@ http://purl.uniprot.org/uniprot/Q62458 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Hapstr1 ^@ http://purl.uniprot.org/uniprot/Q14AM7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a central player within a network of stress response pathways promoting cellular adaptability. The E3 ligase HUWE1 assists HAPSTR1 in controlling stress signaling and in turn, HUWE1 feeds back to promote the degradation of HAPSTR1. HAPSTR1 represents a central coordination mechanism for stress response programs. Functions as a negative regulator of TP53/P53 in the cellular response to telomere erosion and probably also DNA damage. May attenuate p53/TP53 activation through the E3 ubiquitin ligase HUWE1.|||Belongs to the HAPSTR1 family.|||Cytoplasm|||Homooligomer. Heterooligomer with HAPSTR2; the interaction is direct and stabilizes HAPSTR1. Interacts with HUWE1.|||Nucleus|||Ubiquitinated by HUWE1. Promotes HAPSTR1 degradation through polyubiquitination. http://togogenome.org/gene/10090:Gh ^@ http://purl.uniprot.org/uniprot/A0A0M6L0K7|||http://purl.uniprot.org/uniprot/P06880 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the somatotropin/prolactin family.|||Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.|||Secreted http://togogenome.org/gene/10090:Polr3a ^@ http://purl.uniprot.org/uniprot/B2RXC6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the RNA polymerase beta' chain family.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.|||Nucleus http://togogenome.org/gene/10090:Ubl4b ^@ http://purl.uniprot.org/uniprot/Q9CQ84 ^@ Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed specifically in post-meiotic male germ cells of the testis. Abundantly expressed in stage 14-16 spermatids.|||May have arisen from retrotransposition of the X-linked Ubl4a gene during mammalian evolution. http://togogenome.org/gene/10090:Dcun1d5 ^@ http://purl.uniprot.org/uniprot/Q9CXV9 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs). May play a role in DNA damage response and may participate in cell proliferation and anchorage-independent cell growth.|||Highly expressed in testis (PubMed:26906416). Lower expressed in skin, thymus, spleen, lymph nodes and lung (PubMed:26906416).|||Nucleus|||Part of a complex that contains DCUN1D5, CUL1 and RBX1; this interaction is bridged by CUL1. Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Interacts (via DCUN1 domain) with UBE2M (N-terminally acetylated form) and probably with UBE2F (N-terminally acetylated form). May also interact with regulators or subunits of cullin-RING ligases such as RBX1, RNF7, ELOB and DDB1; these interactions are bridged by cullins. Interacts with CAND1; this interaction is bridged by cullins and strongly inhibits the neddylation of cullins. These CAND-cullin-DCNL complexes can only be neddylated in the presence of a substrate adapter.|||Phosphorylation at Ser-41 is independent of cullin's interaction (PubMed:29958295). Phosphorylated in response to both TICAM1 and MYD88 dependent Toll-like receptor (TLR) pathway activation (PubMed:29958295). Phosphorylated in response to IL1B stimulation (By similarity).|||The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D5-cullin and DCUN1D5-E2 interaction affinities.|||spindle http://togogenome.org/gene/10090:Tbca ^@ http://purl.uniprot.org/uniprot/P48428|||http://purl.uniprot.org/uniprot/Q5I0U7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TBCA family.|||Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state.|||Tubulin-folding protein; involved in the early step of the tubulin folding pathway.|||Widely expressed, but is most abundant in the testis.|||cytoskeleton http://togogenome.org/gene/10090:Stx3 ^@ http://purl.uniprot.org/uniprot/Q3UZI9|||http://purl.uniprot.org/uniprot/Q64704 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the syntaxin family.|||Expressed in the retina (at protein level).|||Interacts with REEP6 (PubMed:28369466). Isoform 3B interacts with PRPH2 in rod and cone photoreceptors (PubMed:26406599). Isoform 3B interacts with ROM1 (PubMed:26406599). Isoform 3B interacts with SNAP25 (PubMed:26406599). Isoform 3B interacts with VAMP2 (PubMed:26406599).|||Knockout animals show progressive photoreceptor degeneration. At 5 weeks of age, an approximately 60% decrease in thickness of the outer nuclear layer (ONL) and in the number of ONL neuronal somata is observed, indicating that a large number of photoreceptors have died. In some of the remaining rods, rhodopsin is appropriately localized to the outer segments, but a marked amount of rhodopsin mislocalized to the outer plexiform layer. At 8 and 12 weeks of age, increasing cell loss and further ectopic expression of rhodopsin are observed. Cone photoreceptor loss and ectopic expression of opsin in cones is also observed. Quantification of the progressive degenerative phenotype reveals a rapid loss in the number of neuronal somata in the ONL, indicative of photoreceptor death, whereas the number of cells in the inner nuclear layer, including horizontal, bipolar, and amacrine cells, is no different from that of controls.|||Membrane|||Photoreceptor inner segment|||Potentially involved in docking of synaptic vesicles at presynaptic active zones. Apical receptor involved in membrane fusion of apical vesicles (By similarity). Essential for survival of retinal photoreceetors (PubMed:33974130).|||photoreceptor outer segment http://togogenome.org/gene/10090:Apoc3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1N3|||http://purl.uniprot.org/uniprot/E9QP56|||http://purl.uniprot.org/uniprot/P33622 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the apolipoprotein C3 family.|||Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma. Plays a multifaceted role in triglyceride homeostasis. Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. Formed of several curved helices connected via semiflexible hinges, so that it can wrap tightly around the curved micelle surface and easily adapt to the different diameters of its natural binding partners.|||Secreted|||The most abundant glycoforms are characterized by an O-linked disaccharide galactose linked to N-acetylgalactosamine (Gal-GalNAc), further modified with up to 3 sialic acid residues. Less abundant glycoforms are characterized by more complex and fucosylated glycan moieties. O-glycosylated on Thr-94 with a core 1 or possibly core 8 glycan. http://togogenome.org/gene/10090:Slc38a6 ^@ http://purl.uniprot.org/uniprot/G3UVW3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Amino acid transporter with an apparent selectivity for L-glutamine and L-glutamate. May facilitate glutamine uptake in excitatory neurons. The transport mechanism remains to be elucidated.|||Belongs to the amino acid/polyamine transporter 2 family.|||Cell membrane|||Expressed exclusively in neurons and not in astrocytes and glia cells. Highly expressed in the synapse. Highly expressed in glutamatergic neurons. Primarily expressed in excitatory neurons, with some minor expression in inhibitory neurons.|||Synapse http://togogenome.org/gene/10090:Seh1l ^@ http://purl.uniprot.org/uniprot/Q8R2U0 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as a E3 ubiquitin-protein ligase toward GATOR1. In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex. Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex.|||Belongs to the WD repeat SEC13 family.|||Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13. The SEH1 subunit appears to be only weakly associated with the Nup107-160 subcomplex. Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids. SESN1, SESN2 and SESN3 convey leucine availability via direct interaction with SEH1L and WDR24.|||Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation. This subunit plays a role in recruitment of the Nup107-160 subcomplex to the kinetochore.|||Lysosome membrane|||The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.|||kinetochore|||nuclear pore complex http://togogenome.org/gene/10090:Depdc7 ^@ http://purl.uniprot.org/uniprot/Q91WS7 ^@ Similarity|||Tissue Specificity ^@ Belongs to the DEPDC7 family.|||Strongly expressed in liver and to a lower extent in kidney. http://togogenome.org/gene/10090:Il36g ^@ http://purl.uniprot.org/uniprot/Q3U0P4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-1 family.|||Secreted http://togogenome.org/gene/10090:Nobox ^@ http://purl.uniprot.org/uniprot/Q8VIH1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed from 15.5 dpc.|||Male mice are fertile and show no obvious abnormality. Female mice lacking Nobox have normal gross anatomy and histology, but are infertile with atrophic ovaries that lack oocytes at 6 weeks of age.|||Nucleus|||Specifically expressed in ovaries and testes. In ovaries, expressed in oocytes from primordial through antral follicles but not in granulosa cells, theca cells and corpora lutea.|||Transcription factor which plays an essential role in postnatal follicle development. Binds preferentially to the DNA sequences 5'-TAATTG-3', 5'-TAGTTG-3' and 5'-TAATTA-3'. Directly regulates the transcription of POU5F1 and GDF9 during early folliculogenesis. http://togogenome.org/gene/10090:Vmn1r244 ^@ http://purl.uniprot.org/uniprot/K7N6J2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fgd2 ^@ http://purl.uniprot.org/uniprot/Q8BY35 ^@ Domain|||Function|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Activates JNK1 via CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate.|||Cytoplasm|||Early endosome|||Early endosome membrane|||Intron retention.|||Lymph node, spleen, B-lymphocytes and macrophages (at protein level). Expressed at high levels in lymph node, spleen, B-lymphocytes and bone marrow macrophages. Expressed at lower levels in mature bone marrow dendritic cells. In both immature and mature B-cells, expression is down-regulated by prior B-cell receptor signaling. Expression remains high in resting B and memory cells but declines upon differentiation into plasma cells.|||Nucleus|||The DH domain is necessary for its ability to activate JNK1 via CDC42.|||The FYVE-type zinc-finger is necessary for early endosome localization. Recruitment to endosomal membranes via this domain requires the presence of phosphatidylinositol 3-phosphate or other phosphatidylinositides.|||The PH domain is necessary for localization to the ruffle membrane. Recruitment to ruffle membrane occurs through binding of phosphoinositides by the PH domain. This domain also contributes to the lipid-binding properties of the protein.|||cytoskeleton|||ruffle membrane http://togogenome.org/gene/10090:Defb10 ^@ http://purl.uniprot.org/uniprot/Q8R2I8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Expressed in both adult and neonate brain, and very weakly in kidneys, epididymis, and testis.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:C1qtnf12 ^@ http://purl.uniprot.org/uniprot/Q8R2Z0 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts by activating the Akt signaling in hepatocytes and adipocytes. Not able to increase insulin-stimulated glucose uptake in adipocytes (PubMed:22942287).|||Acts by activating the MAP kinase. Increases insulin-stimulated glucose uptake in adipocytes (PubMed:22942287).|||Belongs to the adipolin/erythroferrone family.|||During adipogenesis. Upon insulin treatment. Up-regulated in obeses mice. Transcription is activated by KLF3 and KLF15.|||Homomultimer; disulfide-linked (PubMed:22942287). Adipolin fC1QTNF12: homotrimer; disulfide-linked (PubMed:22942287). Adipolin gC1QTNF12: homodimer; disulfide-linked (PubMed:22942287). May interact with ERFE.|||Insulin-sensitizing adipocyte-secreted protein (adipokine) that regulates glucose metabolism in liver and adipose tissue. Promotes glucose uptake in adipocytes and suppresses de novo glucose production in hepatocytes via the PI3K-Akt signaling pathway. Administration lead to reduction of blood glucose. Able to attenuate inflammation in fat tissue (PubMed:21849507, PubMed:22275362).|||Processed into Adipolin fC1QTNF12 and Adipolin gC1QTNF12 by FURIN (PubMed:22942287). Insulin enhances endogenous C1QTNF12 cleavage (PubMed:22942287).|||Secreted|||Widely expressed, with high expression in subcutaneous and epididymal white adipose tissues and brown adipose tissue. Expressed in adipocytes (at protein level). http://togogenome.org/gene/10090:Dedd ^@ http://purl.uniprot.org/uniprot/Q3U001|||http://purl.uniprot.org/uniprot/Q9Z1L3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A scaffold protein that directs CASP3 to certain substrates and facilitates their ordered degradation during apoptosis. May also play a role in mediating CASP3 cleavage of KRT18. Regulates degradation of intermediate filaments during apoptosis. May play a role in the general transcription machinery in the nucleus and might be an important regulator of the activity of GTF3C3 (By similarity). Inhibits DNA transcription in vitro.|||Cytoplasm|||Exists predominantly in a mono- or diubiquitinated form.|||Interacts with CASP8, CASP10, KRT8, KRT18, CASP3 and FADD. Homodimerizes and heterodimerizes with DEDD2 (By similarity).|||Ubiquitously expressed.|||nucleolus http://togogenome.org/gene/10090:Rab3ip ^@ http://purl.uniprot.org/uniprot/A0A1W2P7K6|||http://purl.uniprot.org/uniprot/Q68EF0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC2 family.|||Cytoplasm|||Guanine nucleotide exchange factor (GEF) which may activate RAB8A and RAB8B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Mediates the release of GDP from RAB8A and RAB8B but not from RAB3A or RAB5. Modulates actin organization and promotes polarized transport of RAB8A-specific vesicles to the cell surface. Together with RAB11A, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Part of the ciliary targeting complex containing Rab11, ASAP1, RAB3IP and RAB11FIP3 and ARF4 that promotes RAB3IP preciliary vesicle trafficking to mother centriole and ciliogenesis initiation.|||Homodimer (By similarity). Interacts with the N-terminal region of SSX2 (By similarity). Interacts with the GDP-bound forms of RAB8A and RAB8B (By similarity). The interaction with RAB8A is prevented by phosphorylation of RAB8A at 'Thr-72' (By similarity). Interacts with the GDP-bound forms of RAB3A and RAB3D (By similarity). Interacts with DCDC1 (By similarity). Interacts (via the N-terminal region) with TRAPPC14; this interaction mediates RAB3IP association with the TRAPP II complex (By similarity). Forms a heterotetramer with RAB11A where RAB3IP homodimer binds two RAB11A subunits. Forms a complex with RAB11A and RAB11FIP3, probably a heterohexamer with two of each protein subunit, where Rabin8/RAB3IP and RAB11FIP3 simultaneously bind to RAB11A; the complex promotes preciliary trafficking. Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport (By similarity).|||Nucleus|||Vesicle|||centrosome|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Vmn1r195 ^@ http://purl.uniprot.org/uniprot/Q5SVD6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mymx ^@ http://purl.uniprot.org/uniprot/Q2Q5T5 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MYMX family.|||Cell membrane|||Interacts with MYMK (PubMed:28386024).|||Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers (PubMed:28386024, PubMed:28569745, PubMed:28569755, PubMed:30197239). Involved in membrane fusion downstream of the lipid mixing step mediated by MYMK (PubMed:30197239). Acts by generating membrane stresses via its extracellular C-terminus, leading to drive fusion pore formation (PubMed:30197239). Acts independently of MYMK (PubMed:30197239). Involved in skeletal muscle regeneration in response to injury by mediating the fusion of satellite cells, a population of muscle stem cells, with injured myofibers (PubMed:29581287).|||Perinatal death due to a reduction in fused muscle fibers (PubMed:28569745). Embryos are motionless and lack skeletal muscle: they are nearly transparent so that internal organs and bones are apparent (PubMed:28386024). Myocytes differentiate and harbor organized sarcomeres but are fusion-incompetent (PubMed:28386024, PubMed:28569745, PubMed:28569755). Myoblast fusion is impaired downstream of membrane lipid mixing step mediated by Mymk and defects caused by the absence of Mymx are due to impaired fusion pore formation (PubMed:30197239). Conditional deletion in activated muscle stem cells (satellite cells) in adults abolishes satellite cell fusion and prevents muscle regeneration, resulting in severe muscle degeneration after injury (PubMed:29581287).|||Specifically expressed in developing skeletal muscles throughout the limbs and body wall (PubMed:28569745, PubMed:28569755, PubMed:28386024).|||The AxLyCxL motif is required for myoblast fusion.|||Up-regulated during differentiation of myoblasts (PubMed:28569745, PubMed:28569755, PubMed:28386024). During muscle regeneration (PubMed:28569745, PubMed:28569755, PubMed:28386024).|||Was initially reported to be specifically expressed in embryonic stem cells and germ cells (PubMed:16331322). However, it was later shown by different groups that it is specifically expressed in myoblasts where it promotes myoblast fusion (PubMed:28569745, PubMed:28569755, PubMed:28386024). http://togogenome.org/gene/10090:Gns ^@ http://purl.uniprot.org/uniprot/Q8BFR4 ^@ Cofactor|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Lysosome|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. http://togogenome.org/gene/10090:Gpr149 ^@ http://purl.uniprot.org/uniprot/Q3UVY1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Btn2a2 ^@ http://purl.uniprot.org/uniprot/A4QPC6|||http://purl.uniprot.org/uniprot/B9EJ60 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the immunoglobulin superfamily. BTN/MOG family.|||Inhibits the proliferation of CD4 and CD8 T-cells activated by anti-CD3 antibodies, T-cell metabolism and IL2 and IFNG secretion.|||Membrane|||N-glycosylated.|||Widely expressed (at protein level). In the thymus, restricted to the corticomedullary junction, but not confined solely to epithelial cells (at protein level). Significant expression on naive B-cells, splenic natural killer cells, dendritic cells and peritoneal macrophages (at protein level). Negligible expression on naive T-cells up-regulated on activated T-cells (at protein level). http://togogenome.org/gene/10090:Wdfy1 ^@ http://purl.uniprot.org/uniprot/E9Q4P1 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds PtdIns3P in vitro with high specificity over other phosphoinositides (By similarity). Interacts (via WD repeat 2) with tyrosine-phosphorylated TLR3 (via TIR domain) in response to poly(I:C) (PubMed:25736436). Interacts with TLR4 in response to LPS (PubMed:25736436). Interacts with TICAM1 in response to poly(I:C) (PubMed:25736436).|||Early endosome|||Positively regulates TLR3- and TLR4-mediated signaling pathways by bridging the interaction between TLR3 or TLR4 and TICAM1. Promotes TLR3/4 ligand-induced activation of transcription factors IRF3 and NF-kappa-B, as well as the production of IFN-beta and inflammatory cytokines (PubMed:25736436).|||The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched membranes is substantially increased in acidic conditions. The FYVE domain is required for its function in regulating TLR3 signaling. http://togogenome.org/gene/10090:Psmd7 ^@ http://purl.uniprot.org/uniprot/A1L3B8|||http://purl.uniprot.org/uniprot/P26516 ^@ Disease Annotation|||Function|||Miscellaneous|||Similarity|||Subunit ^@ Belongs to the peptidase M67A family.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD7, a base containing 6 ATPases and few additional components. Within the complex, PSMD7 interacts with subunit PSMD4 through their respective MPN domain. Interacts with TRIM5.|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.|||Disruption of the Mov-34 locus is a recessive embryonic lethal mutation.|||Does not bind a metal ion. http://togogenome.org/gene/10090:Or52m1 ^@ http://purl.uniprot.org/uniprot/E9Q546 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tspan15 ^@ http://purl.uniprot.org/uniprot/F7BWT7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tetraspanin (TM4SF) family.|||Cell membrane|||Interacts with ADAM10; the interaction influences ADAM10 substrate specificity.|||Late endosome membrane|||Regulates maturation and trafficking of the transmembrane metalloprotease ADAM10 (PubMed:23035126, PubMed:26668317). Promotes ADAM10-mediated cleavage of (CDH2) (PubMed:26668317). Negatively regulates ligand-induced Notch activity probably by regulating ADAM10 activity (By similarity). http://togogenome.org/gene/10090:Tesmin ^@ http://purl.uniprot.org/uniprot/Q9WTJ6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the lin-54 family.|||Cytoplasm|||Essential for normal spermatogenesis and male fertility (PubMed:31916570). Required for the completion of meiosis in male germ cells (PubMed:31916570).|||Expressed as early as day 8, coincident with the entry of germ cells into meiosis. Expression then progressively increases. Expressed in the pachytene stage.|||Expressed in spermatocytes and adult heart. Also expressed in fetal brain, heart, kidney and ovary.|||Male mice are infertile due to arrested spermatogenesis at the pachytene stage.|||Nucleus|||Testis (at protein level).|||Testis. http://togogenome.org/gene/10090:Sirt1 ^@ http://purl.uniprot.org/uniprot/Q923E4 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at various Lys residues (PubMed:28923965). Deacetylated via an autocatalytic mechanism (PubMed:28923965). Autodeacetylation at Lys-230 promotes its protein deacetylase activity (PubMed:28923965).|||Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity (By similarity). Inhibited by nicotinamide. Negatively regulated by CCAR2 (By similarity).|||Belongs to the sirtuin family. Class I subfamily.|||Binds 1 zinc ion per subunit.|||By calorie restriction which induces endothelial nitric oxide synthase (eNOS) expression. Induced in liver by pyruvate during fasting. Expressed in a circadian manner in the liver with maximal and minimal levels reached at around Zeitgeber time (ZT) 16 and ZT4, respectively. Its deacetylase activity in the liver is also regulated in a circadian manner, with a peak at ZT15. Down-regulated by palmitate; palmitate down-regulation is mediated by the induction of miR-195 that directly targets SIRT1.|||Catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly.|||Cytoplasm|||Deacetylates 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop.|||High degree of embryonic and postnatal lethality. Decreased levels of histone H3 containing a trimethyl group at its lysine 9 position (H3K9me3) in regions of heterochromatin. Attenuates spermatogenesis but not oogenesis with reduced numbers of mature sperm and spermatogenic precursors. Mice develop an autoimmune-like condition with late onset diabetes insipidus. Prostatic intraepithelial neoplasia associated with reduced autophagy. Conditional knockout in POMC neurons leads to an increase of body weight compare to controls when animals are challenged with high-fat diet (PubMed:20620997).|||Interacts with XBP1 isoform 2 (By similarity). Found in a complex with PCAF and MYOD1 Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the interaction disrupts the interaction between SIRT1 and p53/TP53. Interacts with SETD7; the interaction induces the dissociation of SIRT1 from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN, NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient restriction. Interacts with SUZ12; the interaction mediates the association with the PRC4 histone methylation complex which is specific as an association with PCR2 and PCR3 complex variants is not found. Interacts with FOXO1; the interaction deacetylates FOXO1, enhances its DNA-binding ability and increases its transcriptional activity. Interacts with BCL6; leads to a epigenetic repression of specific target genes. Interacts with CLOCK, BMAL1 and PER2. Interacts with PPARA; the interaction seems to be modulated by NAD(+) levels. Interacts with NR1H3 and this interaction is inhibited in the presence of CCAR2. Interacts with CHEK2 and p53/TP53. Exhibits a preferential interaction with sumoylated CCAR2 over its unmodified form (By similarity). Interacts with PACS2 (By similarity). Interacts with SIRT7 (PubMed:28842251, PubMed:28923965). Interacts with PUS7 (By similarity). Interacts with TULP3 (By similarity). Interacts with MORN3; the interaction enhances the ubiquitination of p53/TP53 (By similarity).|||Methylated on multiple lysine residues; methylation is enhanced after DNA damage and is dispensable for deacetylase activity toward p53/TP53.|||Mitochondrion|||NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy (PubMed:11250901, PubMed:11672522, PubMed:12651913, PubMed:12887892, PubMed:12960381, PubMed:15175761, PubMed:15220471, PubMed:15632193, PubMed:15744310, PubMed:15788402, PubMed:16098828, PubMed:16366736, PubMed:16790548, PubMed:16892051, PubMed:17098745, PubMed:17347648, PubMed:17620057, PubMed:17901049, PubMed:17936707, PubMed:18004385, PubMed:18296641, PubMed:18371449, PubMed:18477450, PubMed:18662546, PubMed:18662547, PubMed:18687677, PubMed:19299583, PubMed:19356714, PubMed:20817729, PubMed:21176092, PubMed:21187328, PubMed:21189328, PubMed:21622680, PubMed:23160044, PubMed:20167603, PubMed:28883095). Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression (By similarity). Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively (By similarity). Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction (By similarity). Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT) (PubMed:12887892, PubMed:18477450). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes (By similarity). The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus (PubMed:18004385). Deacetylates 'Lys-266' of SUV39H1, leading to its activation (By similarity). Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 (PubMed:12887892). Deacetylates H2A and 'Lys-26' of H1-4 (By similarity). Deacetylates 'Lys-16' of histone H4 (in vitro) (By similarity). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression (By similarity). Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting (PubMed:21187328). Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1 (By similarity). Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 (By similarity). This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response (By similarity). Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence (PubMed:11672522, PubMed:12960381). Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I (PubMed:11250901). Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability (By similarity). Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation (By similarity). Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis (By similarity). Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing (By similarity). Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha (By similarity). Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 (PubMed:17620057). Deacetylates FOXO1, which increases its DNA binding ability and enhances its transcriptional activity leading to increased gluconeogenesis in liver (PubMed:15220471, PubMed:15788402). Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation (PubMed:16892051). Involved in HES1- and HEY2-mediated transcriptional repression (By similarity). In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' (By similarity). Deacetylates MEF2D (By similarity). Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 (By similarity). Represses HNF1A-mediated transcription (PubMed:21176092). Required for the repression of ESRRG by CREBZF (By similarity). Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed (PubMed:17936707). Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis (By similarity). Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2 (PubMed:15175761). Deacetylates p300/EP300 and PRMT1 (PubMed:15632193, PubMed:28883095). Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation (PubMed:16790548). Involved in liver and muscle metabolism (By similarity). Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis (PubMed:15716268, PubMed:15744310, PubMed:17347648, PubMed:23142079). Involved in regulation of PPARA and fatty acid beta-oxidation in liver (PubMed:19356714). Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2 (PubMed:16098828, PubMed:16366736, PubMed:17901049). Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation (PubMed:17901049). Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression (By similarity). Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2 (By similarity). Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN (By similarity). Promotes DNA double-strand breaks by mediating deacetylation of SIRT6 (By similarity). Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling (By similarity). Transcriptional suppression of TP73 probably involves E2F4 and PCAF (By similarity). Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage (By similarity). Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 (By similarity). Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER) (By similarity). Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria (By similarity). Deacetylates XRCC6/Ku70 at 'Lys-537' and 'Lys-540' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis (By similarity). Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8 (PubMed:18296641, PubMed:21189328). Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation (By similarity). Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1 (PubMed:18687677). Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear (By similarity). In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation (By similarity). Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation (PubMed:17098745). Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability (By similarity). Deacetylates MECOM/EVI1 (By similarity). Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization (By similarity). During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation (By similarity). Regulates the circadian expression of several core clock genes, including BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling (PubMed:18662546, PubMed:18662547, PubMed:19299583). Deacetylates BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator (PubMed:18662546, PubMed:18662547, PubMed:19299583). Deacetylates PER2, facilitating its ubiquitination and degradation by the proteasome (PubMed:18662546). Protects cardiomyocytes against palmitate-induced apoptosis (PubMed:21622680). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (By similarity). Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis (PubMed:30193097). Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 (By similarity). Deacetylates CTNB1 at 'Lys-49' (By similarity). In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (PubMed:20620997). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by mediating protein depropionylation and decrotonylation (PubMed:30026585). Mediates depropionylation of Osterix (SP7) (PubMed:30026585). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase (By similarity). Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity (PubMed:26910618). Involved in the regulation of centrosome duplication. Deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly (By similarity). Deacetylates NDC80/HEC1 (By similarity).|||Nucleus|||PML body|||Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-46 and Thr-522 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-522 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival (PubMed:20167603). Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-46 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity).|||Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).|||S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.|||Widely expressed. Weakly expressed in liver and skeletal muscle. http://togogenome.org/gene/10090:Fam111a ^@ http://purl.uniprot.org/uniprot/Q9D2L9 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autocatalytically cleaved; autocatalytic cleavage takes place in trans.|||Belongs to the FAM111 family.|||Chromosome|||Cytoplasm|||Interacts (via PIP-box) with PCNA; this interaction is direct.|||Nucleus|||Single-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity. DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde. Protects replication fork from stalling by removing DPCs, such as covalently trapped topoisomerase 1 (TOP1) adducts on DNA lesion, or poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors. Required for PCNA loading on replication sites. Promotes S-phase entry and DNA synthesis.|||The PIP-box mediates the interaction with PCNA. http://togogenome.org/gene/10090:Or5b122 ^@ http://purl.uniprot.org/uniprot/Q8VEU6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:3830403N18Rik ^@ http://purl.uniprot.org/uniprot/Q9D6C3 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Hbp1 ^@ http://purl.uniprot.org/uniprot/E9Q1A8|||http://purl.uniprot.org/uniprot/E9Q469|||http://purl.uniprot.org/uniprot/Q8R316 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Binds TCF4 (By similarity). Binds RB1 (PubMed:9178770). Binds the second PAH repeat of SIN3A (PubMed:15235594).|||Nucleus|||Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the histone H1.0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4 (By similarity).|||Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the histone H1.0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4.|||Ubiquitinated by the CTLH E3 ubiquitin-protein ligase complex, leading to subsequent proteasomal degradation. http://togogenome.org/gene/10090:N4bp3 ^@ http://purl.uniprot.org/uniprot/Q8C7U1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the N4BP3 family.|||Binds NEDD4. Interacts with 14-3-3 proteins. Interacts with MAVS.|||Cytoplasmic vesicle|||Plays a positive role in the antiviral innate immune signaling pathway. Mechanistically, interacts with MAVS and functions as a positive regulator to promote 'Lys-63'-linked polyubiquitination of MAVS and thus strengthens the interaction between MAVS and TRAF2 (By similarity). Also plays a role in axon and dendrite arborization during cranial nerve development. May also be important for neural crest migration and early development of other anterior structures including eye, brain and cranial cartilage (By similarity).|||axon|||dendrite http://togogenome.org/gene/10090:Otub2 ^@ http://purl.uniprot.org/uniprot/Q9CQX0 ^@ Function|||Similarity ^@ Belongs to the peptidase C65 family.|||Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains (By similarity). http://togogenome.org/gene/10090:Gnl2 ^@ http://purl.uniprot.org/uniprot/Q3V3N5|||http://purl.uniprot.org/uniprot/Q99LH1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class YlqF/YawG GTPase family. NOG2 subfamily.|||GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation.|||GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation. May promote cell proliferation possibly by increasing p53/TP53 protein levels, and consequently those of its downstream product CDKN1A/p21, and decreasing RPL23A protein levels.|||Interacts with LYAR and RPL23A. Interacts with the nuclear importin-beta receptor and, at a lower extent, with importin-alpha.|||nucleolus http://togogenome.org/gene/10090:Nelfb ^@ http://purl.uniprot.org/uniprot/Q8C4Y3 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the NELF-B family.|||Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (Pol II) (PubMed:25773599). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (By similarity). May be able to induce chromatin unfolding (By similarity). Essential for early embryogenesis; plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) by preventing unscheduled expression of developmental genes (PubMed:19340312). Plays a key role in establishing the responsiveness of stem cells to developmental cues; facilitates plasticity and cell fate commitment in ESCs by establishing the appropriate expression level of signaling molecules (PubMed:25773599). Supports the transcription of genes involved in energy metabolism in cardiomyocytes; facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes (PubMed:24656816).|||Isoform 1 is expressed in the kidney, liver, adipose and lung (PubMed:26010750). Isoform 2 is widely expressed (PubMed:26010750).|||Mice exhibit early embryonic lethality (PubMed:25773599, PubMed:19340312). Knockdown in embryonic stem cells (ESCs) leads to proliferation defects, increased differentiation, increased expression of development-associated genes and the dysregulation of genes involved in signaling and metabolic pathways (PubMed:25773599, PubMed:19340312). Mice exhibit cardiomyopathy, impaired response to cardiac stress and the reduced expression of metabolism-related genes in cardiomyocytes (PubMed:24656816).|||Nucleus|||Produced by alternative initiation at a CTG start codon.|||The NELF complex is composed of NELFA, NELFB, NELFCD and NELFE; the N-terminus of NELFB binds to the NELFA:NELFCD subcomplex (By similarity). Binds RNA which may help to stabilize the NELF complex on nucleic acid (By similarity) Interacts with the first BRCT repeat of BRCA1 (By similarity). Interacts with KIAA1191 (By similarity). Isoform 1 and isoform 2 interact with NELFA, NELFCD and NELFE (PubMed:26010750). http://togogenome.org/gene/10090:Or4c104 ^@ http://purl.uniprot.org/uniprot/Q8VF94 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Minar2 ^@ http://purl.uniprot.org/uniprot/Q8C4X7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MINAR family.|||Binds cholesterol and may regulate the distribution and homeostasis of cholesterol in hair cells (By similarity). May play a role in angiogenesis (By similarity).|||Endoplasmic reticulum membrane|||In an experimental Parkinson's disease model, homozygous knockout mice lacking Minar2 display severe motor deficits such as rigidity and bradykinesia, gait abnormalities, reduced spontaneous locomotor and exploratory behavior (PubMed:32954300). Homozygous knockout mice lacking Minar2 present with rapidly progressive sensorineural hearing loss (HL) associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age (PubMed:35727972).|||Interacts with NOTCH2.|||Lysosome membrane|||Widely expressed in the cortex and Purkinje cells of cerebellum (PubMed:32954300). Expressed in the inner ear, mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis (PubMed:35727972). http://togogenome.org/gene/10090:Polr2e ^@ http://purl.uniprot.org/uniprot/Q3V214|||http://purl.uniprot.org/uniprot/Q80UW8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family.|||Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively. In RNA Pol II, this subunit is present in 2-fold molar excess over the other subunits. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with URI1.|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process.|||Nucleus http://togogenome.org/gene/10090:Igll1 ^@ http://purl.uniprot.org/uniprot/P20764 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Critical for B-cell development.|||Endoplasmic reticulum|||Interacts with VPREB1 (By similarity). Interacts with SYNV1/HRD1 (via N-terminus); this interaction leads to increased IGLL1 ubiquitination and degradation in pre-B cells, possibly through a lysosomal, not proteasomal, pathway (PubMed:29907570).|||Secreted|||Selectively expressed in pre-B lymphocytes. http://togogenome.org/gene/10090:Mus81 ^@ http://purl.uniprot.org/uniprot/Q91ZJ0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the XPF family.|||Expressed highly in testis. Expressed also in bone marrow, brain, thymus and to a lesser extent in heart and skeletal muscle, colon, kidney and spleen.|||Interacts with EME1 and EME2 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks.|||May self-associate. Interacts with CHEK2. Interacts with BLM, and this interaction may stimulate the endonuclease activity of MUS81. Interacts with EME2. Interacts with SLX4/BTBD12; this interaction is direct and links the MUS81-EME1 complex to SLX4, which may coordinate the action of the structure-specific endonuclease during DNA repair. Interacts with DCLRE1B/Apollo (By similarity). Interacts with EME1. Interacts with RECQL5; this interaction stimulates mitotic DNA synthesis (By similarity).|||nucleolus http://togogenome.org/gene/10090:Zfp369 ^@ http://purl.uniprot.org/uniprot/F8VQL6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus http://togogenome.org/gene/10090:Myh3 ^@ http://purl.uniprot.org/uniprot/P13541 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).|||Muscle contraction.|||Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||Represents a conventional myosin. This protein should not be confused with the unconventional myosin-3 (MYO3).|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||myofibril http://togogenome.org/gene/10090:Or10d1 ^@ http://purl.uniprot.org/uniprot/Q9EQ86 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Serpina3j ^@ http://purl.uniprot.org/uniprot/D3Z451 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Cdhr1 ^@ http://purl.uniprot.org/uniprot/Q8VHP6 ^@ Disruption Phenotype|||Function|||PTM|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in cone and rod photoreceptor cells (at protein level). Expressed in photoreceptor cells of the outer nuclear layer of the retina. Expressed in mitral and tufted cells in the olfactory bulb.|||Interacts with PROM1.|||Mice have no obvious phenotype but show photoreceptor cell death as early as 1 month of age shortly after completion of retinal development. Its absence severely compromises the structure of OS which are disorganized and fragmented, but the consequences on photoreceptor electrical signaling are very mild. Proteolytic cleavage is partially inhibited in the absence of orderly OS assembly in mouse retinas lacking RDS/peripherin.|||Partially unspliced pre-RNA.|||Potential calcium-dependent cell-adhesion protein. May be required for the structural integrity of the outer segment (OS) of photoreceptor cells.|||Undergoes proteolytic cleavage; produces a soluble 95 kDa N-terminal fragment and a 25 kDa cell-associated C-terminal fragment. http://togogenome.org/gene/10090:Arhgef39 ^@ http://purl.uniprot.org/uniprot/Q66JY6 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Promotes cell proliferation. http://togogenome.org/gene/10090:Arid4b ^@ http://purl.uniprot.org/uniprot/A2CG63 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the Sin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4A (PubMed:17043311). Involved in spermatogenesis, together with ARID4A, where it functions as a transcriptional coactivator for AR (androgen receptor) and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (PubMed:23487765). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (PubMed:18728284).|||Component of a Sin3A corepressor complex consisting of SIN3A, SAP130, SUDS3/SAP45, SAP180, HDAC1 and HDAC2 (By similarity). Interacts with ARID4A (PubMed:17043311). Interacts with AR (PubMed:23487765).|||Embryonic lethal. Lethality occurs between embryonic day E3.5 and E7.5 (PubMed:17043311). Heterozygous males are fully fertile (PubMed:23487765). Double knockouts of ARID4B heterozygotes with ARID4A homozygotes show various hematological abnormalities, which are more severe than the ARID4A phenotype alone. Hematopoietic stem cell (HSC) and common myeloid progenitor (CMP) counts in bone marrow and spleen are increased. Lymphocyte numbers in spleen are significantly reduced. In peripheral blood, red blood cell counts and lymphocyte counts are reduced. Approximately 83% of animals develop acute myeloid leukemia (AML) and/or myeloid sarcoma. In bone marrow cells, expression of FOXP3 is significantly reduced (PubMed:18728284). Expression of HOXB3, HOXB5, HOXB6, HOXB8 and PITX2 in bone marrow cells is reduced (PubMed:17043311). Males show progressive reduction in fertility from 2 months of age onwards, with reduced testis size and variable defects in seminal vesicle formation. Spermatogenesis is partially blocked from the meiosis II stage onwards leading to reduced numbers of mature spermatozoa. Expression in testis of CLDN3, an androgen receptor-regulated gene, is significantly reduced. Expression of PTGDS is also reduced, whereas expression of INHA and EMB is moderately increased (PubMed:23487765).|||Expressed in Sertoli cells of the testis.|||Nucleus|||The ARID domain is involved in stabilizing the mSin3A corepressor complex on DNA.|||The C-terminus mediates interaction with mSin3A corepressor complex.|||The N-terminus is involved in transcriptional repression by HDAC-independent mechanisms. http://togogenome.org/gene/10090:P2ry4 ^@ http://purl.uniprot.org/uniprot/Q0VBT7|||http://purl.uniprot.org/uniprot/Q9JJS7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the liver, intestine, stomach, bladder and lung.|||Membrane|||Phosphorylation of Ser-329 and Ser-330 is a key step in agonist-dependent desensitization and loss of surface P2RY4. This phosphorylation does not involve PKC, nor other calcium-activated kinases (By similarity).|||Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Or6c213 ^@ http://purl.uniprot.org/uniprot/Q8VFI2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Apoo ^@ http://purl.uniprot.org/uniprot/Q9DCZ4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the apolipoprotein O/MICOS complex subunit Mic27 family.|||Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Plays a crucial role in crista junction formation and mitochondrial function (By similarity). Can induce cardiac lipotoxicity by enhancing mitochondrial respiration and fatty acid metabolism in cardiac myoblasts (PubMed:24743151). Promotes cholesterol efflux from macrophage cells. Detected in HDL, LDL and VLDL. Secreted by a microsomal triglyceride transfer protein (MTTP)-dependent mechanism, probably as a VLDL-associated protein that is subsequently transferred to HDL (By similarity).|||Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with IMMT/MIC60. Interacts with MICOS10/MIC10 and APOOL/MIC27.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Mitochondrion|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Dydc1 ^@ http://purl.uniprot.org/uniprot/E0CXB0|||http://purl.uniprot.org/uniprot/Q9D9T0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the dpy-30 family.|||Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB (PubMed:36417862). Interacts with SH3GL3 (By similarity).|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:36417862). Plays a crucial role during acrosome biogenesis (PubMed:19545932).|||flagellum axoneme http://togogenome.org/gene/10090:Gzmf ^@ http://purl.uniprot.org/uniprot/P08883 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytolytic granule|||This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. http://togogenome.org/gene/10090:Orc4 ^@ http://purl.uniprot.org/uniprot/O88708|||http://purl.uniprot.org/uniprot/Q8C693 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ORC4 family.|||Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 (By similarity). Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.|||Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase (By similarity). Interacts with DBF4 (PubMed:12614612). Interacts with POLQ (By similarity).|||Component of the origin recognition complex (ORC) that binds origins of replication.|||Nucleus http://togogenome.org/gene/10090:Vmn2r57 ^@ http://purl.uniprot.org/uniprot/L7N269 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Muc20 ^@ http://purl.uniprot.org/uniprot/Q8BUE7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Highly expressed in kidney. Up-regulated in renal tissues during renal injury.|||Interacts with MET; oligomerization increases affinity for MET.|||May regulate MET signaling cascade. Seems to decrease hepatocyte growth factor (HGF)-induced transient MAPK activation. Blocks GRB2 recruitment to MET thus suppressing the GRB2-RAS pathway. Inhibits HGF-induced proliferation of MMP1 and MMP9 expression (By similarity).|||Secreted|||microvillus membrane http://togogenome.org/gene/10090:Aopep ^@ http://purl.uniprot.org/uniprot/Q8BXQ6 ^@ Caution|||Cofactor|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A paper describing the expression patterns of this protein has been retracted due to concerns of image manipulation.|||Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.|||Belongs to the peptidase M1 family.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Expressed in testis, heart, brain, lung, liver, skeletal muscle, kidney and ovary. Expressed in vascular tissues.|||Intron retention. This sequence is incomplete at the 5'-end and differs from that shown at positions 658-661.|||nucleolus http://togogenome.org/gene/10090:Colgalt2 ^@ http://purl.uniprot.org/uniprot/Q6NVG7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 25 family.|||Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of collagen.|||Endoplasmic reticulum lumen http://togogenome.org/gene/10090:Hoxd12 ^@ http://purl.uniprot.org/uniprot/P23812 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Expressed during development of the posterior part of the body.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Pcnx ^@ http://purl.uniprot.org/uniprot/A0A1Y7VKR5|||http://purl.uniprot.org/uniprot/Q9QYC1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the pecanex family.|||Membrane http://togogenome.org/gene/10090:Ctnnbip1 ^@ http://purl.uniprot.org/uniprot/Q9JJN6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CTNNBIP1 family.|||Binds CTNNB1.|||Cytoplasm|||Highly expressed in heart, brain, liver and skeletal muscle. Detected at low levels in kidney, testis and lung.|||Nucleus|||Prevents the interaction between CTNNB1 and TCF family members, and acts as negative regulator of the Wnt signaling pathway. http://togogenome.org/gene/10090:Usb1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0E0|||http://purl.uniprot.org/uniprot/Q91W78 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ 3'-5' RNA exonuclease that trims the 3' end of oligo(U) and oligo(A) tracts of the pre-U6 small nuclear RNA (snRNA) molecule, leading to the formation of a mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. Participates in the U6 snRNA 3' end processing that prevents U6 snRNA degradation. In addition also removes uridines from the 3' end of U6atac snRNA and possibly the vault RNA VTRNA1-1.|||Belongs to the 2H phosphoesterase superfamily. USB1 family.|||Interacts with PLRG1, CDC5L and PRPF19.|||Nucleus|||Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA 3' end-terminated with a 2',3'-cyclic phosphate. http://togogenome.org/gene/10090:Cflar ^@ http://purl.uniprot.org/uniprot/O35732|||http://purl.uniprot.org/uniprot/Q812G4 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Apoptosis regulator protein which may function as a crucial link between cell survival and cell death pathways in mammalian cells. Acts as an inhibitor of TNFRSF6 mediated apoptosis. A proteolytic fragment (p43) is likely retained in the death-inducing signaling complex (DISC) thereby blocking further recruitment and processing of caspase-8 at the complex. Full length and shorter isoforms have been shown either to induce apoptosis or to reduce TNFRSF-triggered apoptosis. Lacks enzymatic (caspase) activity (By similarity).|||At 9.5 and 10.5 dpc, highly expressed in developing heart.|||Belongs to the peptidase C14A family.|||Highly expressed in heart.|||Isoform 1 but not isoform 2 is activated by BCR cross-linking in primary B-cells.|||Proteolytically processed by CASP8 generating subunits p43 and p12.|||TNFRSF6 stimulation triggers recruitment to the death-inducing signaling complex (DISC) formed by TNFRSF6, FADD and CASP8 (By similarity). A proteolytic fragment (p43) stays associated with the DISC (By similarity). Interacts with RIPK1 (PubMed:31519887).|||The caspase domain lacks the active site residues involved in catalysis. http://togogenome.org/gene/10090:Mmp11 ^@ http://purl.uniprot.org/uniprot/Q02853|||http://purl.uniprot.org/uniprot/Q3UQT3 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M10A family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||May play an important role in the progression of epithelial malignancies.|||Specifically expressed in the mammary gland during apoptosis.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||extracellular matrix http://togogenome.org/gene/10090:Lcp1 ^@ http://purl.uniprot.org/uniprot/Q61233 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Actin-binding protein. Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28. Modulates the cell surface expression of IL2RA/CD25 and CD69.|||Cell junction|||Cell projection|||Monomer (By similarity). Interacts with AIF1 (PubMed:14756805). Interacts with actin (By similarity).|||Phosphorylated on a serine residue in response to costimulation through TCR/CD3 and CD2 or CD28. Serine phosphorylation promotes association with the actin cytoskeleton and targeting to peripheral cell projections (By similarity).|||cytoskeleton|||ruffle membrane http://togogenome.org/gene/10090:Cct4 ^@ http://purl.uniprot.org/uniprot/P80315|||http://purl.uniprot.org/uniprot/Q564F4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG (By similarity). Interacts with DNAAF4 (PubMed:23872636). Interacts with DLEC1 (By similarity).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. The TRiC complex plays a role in the folding of actin and tubulin.|||Cytoplasm|||Melanosome|||The N-terminus is blocked.|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Rab5b ^@ http://purl.uniprot.org/uniprot/P61021 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Binds EEA1. Interacts with RIN2 and RIN3, which probably regulate its pathway, possibly by acting as GEFs (By similarity). Interacts with GDI1, GDI2, CHML and CHM; phosphorylation at Ser-84 disrupts this interaction (By similarity).|||Cell membrane|||Early endosome membrane|||Melanosome|||Phosphorylation of Ser-84 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||Protein transport (By similarity). Probably involved in vesicular traffic (By similarity).|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. http://togogenome.org/gene/10090:Or13g1 ^@ http://purl.uniprot.org/uniprot/Q7TS01 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Or1e31 ^@ http://purl.uniprot.org/uniprot/A0A0U1RNJ4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Reep5 ^@ http://purl.uniprot.org/uniprot/G3X8R0|||http://purl.uniprot.org/uniprot/Q9CQG4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the DP1 family.|||Membrane http://togogenome.org/gene/10090:Polm ^@ http://purl.uniprot.org/uniprot/Q9JIW4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the DNA polymerase type-X family.|||DPOLM has a reduced ability to distinguish dNTP and rNTP as substrates, and elongates them on DNA primer strand with a similar efficiency. It is able to polymerize nucleotides on RNA primer strands (By similarity).|||Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.|||Nucleus http://togogenome.org/gene/10090:Sgo2a ^@ http://purl.uniprot.org/uniprot/Q7TSY8 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shugoshin family.|||Contaminating sequence. Potential poly-A sequence.|||Cooperates with PPP2CA to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Has a crucial role in protecting REC8 at centromeres from cleavage by separase. During meiosis, protects centromeric cohesion complexes until metaphase II/anaphase II transition, preventing premature release of meiosis-specific REC8 cohesin complexes from anaphase I centromeres. Is thus essential for an accurate gametogenesis. May act by targeting PPP2CA to centromeres, thus leading to cohesin dephosphorylation. Essential for recruiting KIF2C to the inner centromere and for correcting defective kinetochore attachments. Involved in centromeric enrichment of AUKRB in prometaphase.|||Interacts with PPP2CA. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with CDCA8 (By similarity).|||Mice develop normally and survive to adulthood without any apparent alteration. However, both males and females are infertile. This defect appears cytologically as complete loss of centromere cohesion at metaphase II, leading to single chromatids, and physiologically as formation of aneuploid gametes that gave rise to infertility.|||Nucleus|||Shugoshin is Japanese for guardian spirit (as it is known to be a protector of centromeric cohesin).|||Ubiquitously expressed in proliferating cells. Highly expressed in the testis and oocytes.|||centromere|||kinetochore http://togogenome.org/gene/10090:Gpm6b ^@ http://purl.uniprot.org/uniprot/A2AEG3|||http://purl.uniprot.org/uniprot/A2AEG6|||http://purl.uniprot.org/uniprot/P35803|||http://purl.uniprot.org/uniprot/Q3US81|||http://purl.uniprot.org/uniprot/Q3V0Z9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the myelin proteolipid protein family.|||Cell membrane|||First detected in presumptive postmitotic neurons in the developing neural tube at embryonic day 9.|||Interacts with SERT.|||May be involved in neural development. Involved in regulation of osteoblast function and bone formation. Involved in matrix vesicle release by osteoblasts; this function seems to involve maintenance of the actin cytoskeleton. May be involved in cellular trafficking of SERT and thereby in regulation of serotonin uptake.|||Membrane|||Widely expressed. In the brain, expressed in neurons and oligodendrocytes. http://togogenome.org/gene/10090:Mrpl39 ^@ http://purl.uniprot.org/uniprot/Q9JKF7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL39 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Tnks2 ^@ http://purl.uniprot.org/uniprot/Q3UES3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.|||Belongs to the ARTD/PARP family.|||Cytoplasm|||Golgi apparatus membrane|||Nucleus|||Oligomerizes and associates with TNKS. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of Grb14 and TRF1 with its ankyrin repeat region. Interacts with HIF1AN. Interacts with RNF146; this interaction leads to ubiquitination and proteasomal degradation. Interacts with NUMA1 (By similarity).|||Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity.|||Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation.|||telomere http://togogenome.org/gene/10090:Greb1l ^@ http://purl.uniprot.org/uniprot/B9EJV3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ At 15.5 dpc, expressed in kidney, ureter and bladder (PubMed:29100090). At 16.0 dpc, strong expression in the liver, thymus, intestine, kidney, and brain. In the brain, high levels in the ventricular zone and in the neopallial cortex. In the kidney, highest levels in the nephrogenic zone located in the cortical region of the kidney. Also observed in epithelial cells of the differentiating renal tubules. At P0, strong expression in the nephrogenic zone (PubMed:29100091). In the inner ear, prominent expression is observed between 13 and 16 dpc (PubMed:29955957).|||Belongs to the GREB1 family.|||Embryonic lethal at the homozygous state. At 13.5 dpc, all homozygous embryos are significantly smaller compared to wild-type and heterozygous littermates and present with exencephaly. Male and female embryos lack kidney and show absence of Wolffian and Muellerian ducts, respectively. However, mesonephric tubules are consistently observed. Some potential remnants of ureteric bud are present in most mutant embryos. In male mutant embryos, the gonads are severely affected, being small and with poorly organized sex-cords compared to wild-type littermates. Mutant embryos also show cardiac morphogenesis defects with superimposed ventricles.|||Expressed in the inner ear, with a high presence in the spiral ganglia, cochlear nerve bundles, and hair cells.|||Membrane|||Plays a major role in early metanephros and genital development. http://togogenome.org/gene/10090:Relch ^@ http://purl.uniprot.org/uniprot/Q148V7 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Interacts with RAB11A (VIA-GTP form) (PubMed:29514919). Interacts with RAB11B (PubMed:29514919). Interacts (via the third HEAT repeat) with OSBP (via C-terminus) (PubMed:29514919). Found in a complex composed of RELCH, OSBP1 and RAB11A (PubMed:29514919).|||Recycling endosome|||Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP. Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes.|||The sequence differs from that shown because it is derived from pre-RNA.|||trans-Golgi network http://togogenome.org/gene/10090:Ikzf4 ^@ http://purl.uniprot.org/uniprot/Q8C208 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Ikaros C2H2-type zinc-finger protein family.|||C-terminal zinc fingers mediate homodimerization.|||DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-binding sequence. Interacts with SPI1 and MITF to repress transcription of the CTSK and ACP5 promoters via recruitment of corepressors SIN3A and CTBP2. May be involved in the development of central and peripheral nervous systems. Essential for the inhibitory function of regulatory T-cells (Treg). Mediates FOXP3-mediated gene silencing in regulatory T-cells (Treg) via recruitment of corepressor CTBP1 (PubMed:19696312).|||Eos is a Greek word for rising sun.|||Expressed mainly in the brain. Up-regulated in long term cultured astrocytes. Down-regulated during osteoclast differentiation.|||Highly expressed in the brain at 15 dpc and 18 dpc. Expression gradually decreased as postnatal development proceeded. No expression detected in the liver, kidney, lung, thymus or spleen during all developmental stages.|||Nucleus|||Self-associates. Interacts with other family members; IKZF1, IKZF2, IKZF3 and IKZF5 (By similarity). Interacts with CTBP2, SPI1 and MITF. Interacts with FOXP3 and CTBP1.|||The N-terminal zinc fingers are involved in sequence-specific DNA binding. http://togogenome.org/gene/10090:Pigx ^@ http://purl.uniprot.org/uniprot/F6YX19|||http://purl.uniprot.org/uniprot/Q99LV7 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGX family.|||Endoplasmic reticulum membrane|||Essential component of glycosylphosphatidylinositol-mannosyltransferase 1 which transfers the first of the 4 mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis.|||Essential component of glycosylphosphatidylinositol-mannosyltransferase 1 which transfers the first of the 4 mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Probably acts by stabilizing the mannosyltransferase PIGM (By similarity).|||Interacts with PIGM.|||N-glycosylated.|||Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon. http://togogenome.org/gene/10090:Grk3 ^@ http://purl.uniprot.org/uniprot/Q3UYH7|||http://purl.uniprot.org/uniprot/Q8BVT9 ^@ Function|||PTM|||Similarity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.|||Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors.|||Ubiquitinated. http://togogenome.org/gene/10090:Tnfrsf12a ^@ http://purl.uniprot.org/uniprot/Q9CR75 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with TRAF1 and TRAF2, and probably also with TRAF3.|||By FGF-1.|||Highly expressed in fetal heart, intestine, kidney, liver, lung and skin, and in adult heart and ovary. Intermediate expression in adult kidney, lung and skin.|||Membrane|||Receptor for TNFSF12/TWEAK (By similarity). Weak inducer of apoptosis in some cell types. Promotes angiogenesis and the proliferation of endothelial cells. May modulate cellular adhesion to matrix proteins. http://togogenome.org/gene/10090:Cyp2a12 ^@ http://purl.uniprot.org/uniprot/P56593 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Highly active in the 7-alpha-hydroxylation of testosterone.|||Liver.|||Microsome membrane http://togogenome.org/gene/10090:Mtmr1 ^@ http://purl.uniprot.org/uniprot/Q9Z2C4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cell membrane|||Cytoplasm|||Homodimer.|||Lipid phosphatase that has high specificity for phosphatidylinositol 3-phosphate and has no activity with phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:12217958). Activity with phosphatidylinositol (3,5)-bisphosphate is controversial; it has been shown for the human ortholog (By similarity). In contrast, PubMed:12217958 find no activity with this substrate.|||The C-terminal region is required for dimerization.|||Widely expressed. Detected in skeletal muscle, heart, lung, liver and brain. http://togogenome.org/gene/10090:Vmn1r163 ^@ http://purl.uniprot.org/uniprot/K9J7G0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cldn34b1 ^@ http://purl.uniprot.org/uniprot/B1AZQ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Or7c19 ^@ http://purl.uniprot.org/uniprot/Q8VGB8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Minar1 ^@ http://purl.uniprot.org/uniprot/Q8K3V7 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MINAR family.|||Cell membrane|||Expressed in brain and in islets of Langerhans.|||Interacts with NOTCH2; this interaction increases MINAR1 stability. Interacts (via N-terminus) with DEPTOR (via PDZ domain); this interaction may stabilize DEPTOR protein by impairing its ubiquitination.|||Intrinsically disordered protein which may negatively regulate mTOR signaling pathway by stabilizing the mTOR complex component DEPTOR. Negatively regulates angiogenesis. Negatively regulates cell growth (By similarity). Negatively regulates neurite outgrowth in hippocampal neurons (By similarity).|||MINAR1 topology is a matter of debate, some authors think the N-terminus is extracellular, while preliminary experimental results suggest a cytosolic location. http://togogenome.org/gene/10090:Saal1 ^@ http://purl.uniprot.org/uniprot/Q9D2C2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SAAL1 family.|||Expressed in the synovial tissue of knee joints.|||Nucleus|||Plays a role in promoting the proliferation of synovial fibroblasts in response to pro-inflammatory stimuli. http://togogenome.org/gene/10090:Numa1 ^@ http://purl.uniprot.org/uniprot/E9Q7G0 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosylated by TNKS at the onset of mitosis; ADP-ribosylation is not required for its localization to spindle poles.|||Cell membrane|||Chromosome|||Expressed in testis, speen, liver, lung, spinal cord and brain. Expressed in Purkinje neurons (at protein level) (PubMed:19255246).|||Homodimer. Also forms multiarm oligomers by association of C-terminal tail domains, oligomers may further assemble to form a hexagonal nuclear lattice-like network. Associates with the dynein-dynactin complex; this association promotes the transport and accumulation of NUMA1 at the mitotic spindle poles that is inhibited by the BRISC complex in a PLK1-dependent manner. Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (By similarity). Interacts (via C-terminus) with microtubules (MTs); this interaction is direct and promotes both MT bundle formation and stability in a dynein-dynactin complex- and CDK1-independent manner. Interacts with EPB41 and EPB41L2; these interactions are negatively regulated by CDK1 during metaphase and are important for anaphase-specific localization of NUMA1 in symmetrically dividing cells. Interacts (via C-terminus) with GPSM2 (via TPR repeats); this interaction is direct, prevented by competitive binding of INSC, is inhibited in a PLK1-dependent manner, blocks the association of NUMA1 with MTs and inhibits NUMA1-induced MT bundle formation, prevents the association of NUMA1 with SPAG5, induces mitotic spindle pole localization of GPSM2, both metaphase cell cortex localization of NUMA1 and mitotic spindle organization. Does not interact with GPSM2 during anaphase. Interacts (via C-terminus) with the nuclear importin alpha/importin beta receptor; this interaction is inhibited by RanGTP. Interacts (via C-terminus) with KPNB1; this interaction is inhibited by RanGTP and the BRISC complex. Interacts with ABRAXAS2 and the BRISC complex; these interactions regulate mitotic spindle assembly. Interacts (via N-terminal end of the coiled-coil domain) with RAE1; this interaction promotes mitotic spindle formation. Interacts (via C-terminus) with SPAG5 (via C-terminus); this interaction promotes the recruitment of SPAG5 to the MTs at spindle poles in a dynein-dynactin-dependent manner and regulates mitotic spindle organization and proper chromosome alignment during mitosis. Interacts with TNKS; this interaction occurs at the onset of mitosis. Interacts with TNKS2. Interacts with tubulin. Interacts with KHDC3 (via C-terminus) (PubMed:25936915).|||Lateral cell membrane|||Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:19255246, PubMed:24109598, PubMed:26765568). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:26765568). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:24109598, PubMed:26765568). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation. Binds also to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (By similarity). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:26765568). Plays a role in mitotic MT aster assembly. Involved in anastral spindle assembly. Positively regulates TNKS protein localization to spindle poles in mitosis. Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (By similarity). Required for epidermal differentiation and hair follicle morphogenesis (PubMed:26765568).|||Mutant mice with an internal in-frame deletion of exon 22 exhibit early embryonic lethality (PubMed:19255246). Mutant mice with a conditional internal in-frame deletion of exon 22 show embryonic lethality and display inhibition of primary embryonic fibroblast proliferation that display mitotic centrosome-spindle coupling, microtubule-focusing at the spindle poles and equatorial metaphase chromosome alignement defects (PubMed:19255246). Mutant mice with a conditional internal in-frame deletion of exon 22 in the embryonic epidermis show neonatal lethality and display perturbation of epidermis differentiation characterized by increased suprabasal cell divisions and mitotic spindle orientation defects (PubMed:26765568). Adult mutant mice with a conditional internal in-frame deletion of exon 22 in interfollicular and hair follicles display an almost complete absence of hair regrowth and mitotic spindle orientation defects in hair follicle matrix cells (PubMed:26765568).|||Nucleus|||Nucleus matrix|||O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status.|||Phosphorylation and dephosphorylation on Thr-2037 regulates the extent of cortical NUMA1 and the dynein-dynactin complex localization during mitotic metaphase and anaphase. In metaphase, phosphorylation on Thr-2037 occurs in a kinase CDK1-dependent manner; this phosphorylation maintains low levels of cortical dynein-dynactin complex at metaphase, and hence proper spindle positioning. In anaphase, dephosphorylated on Thr-2037 by phosphatase PPP2CA; this dephosphorylation stimulates its membrane association and with the dynein-dynactin complex its enrichment at the cell cortex, and hence robust spindle elongation. Probably also phosphorylated on Thr-1997 and Ser-2069 by CDK1; these phosphorylations may regulate its cell cortex recruitment during metaphase and anaphase. Phosphorylated on Ser-1751, Ser-1754, Ser-1771 and Ser-1816 by PLK1; these phosphorylations induce cortical dynein-dynactin complex dissociation from the NUMA1-GPSM2 complex and negatively regulates cortical dynein-dynactin complex localization.|||The C-terminal tubulin-binding domain mediates direct binding to microtubules, independently of dynein-dynactin complex, and induces their bundling and stabilization. The 4.1-binding domain is necessary for its cortical stability and spindle orientation.|||Ubiquitinated with 'Lys-63'-linked polyubiquitin chains. Deubiquitination by the BRISC complex is important for the incorporation of NUMA1 into mitotic spindle poles and normal spindle pole function, probably by modulating interactions between NUMA1, dynein-dynactin complex and importin-beta.|||cell cortex|||centrosome|||cytoskeleton|||nucleoplasm|||spindle pole http://togogenome.org/gene/10090:Zbtb41 ^@ http://purl.uniprot.org/uniprot/Q811F1 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Cpsf7 ^@ http://purl.uniprot.org/uniprot/Q8BTV2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Asymmetrically dimethylated on arginine residues by PRMT1.|||Belongs to the RRM CPSF6/7 family.|||Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. CPSF7 activates directly the mRNA 3'-processing machinery. Binds to pA signals in RNA substrates.|||Component of the cleavage factor Im (CFIm) complex which is a heterotetramer composed of two subunits of NUDT21/CPSF5 and two subunits of CPSF6 or CPSF7 or a heterodimer of CPSF6 and CPSF7. The cleavage factor Im (CFIm) complex associates with the CPSF and CSTF complexes to promote the assembly of the core mRNA 3'-processing machinery. Interacts with NUDT21/CPSF5. Interacts (via Arg/Ser-rich domain) with FIP1L1 (preferentially via unphosphorylated form and Arg/Glu/Asp-rich region); this interaction mediates, at least in part, the interaction between the CFIm and CPSF complexes and may be inhibited by CPSF7 hyper-phosphorylation.|||Contains an Arg/Ser-rich domain composed of arginine-serine dipeptide repeats within the C-terminal region that is necessary and sufficient for activating mRNA 3'-processing.|||Cytoplasm|||Nucleus|||Phosphorylated. http://togogenome.org/gene/10090:Tmem247 ^@ http://purl.uniprot.org/uniprot/Q497K7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fscn3 ^@ http://purl.uniprot.org/uniprot/Q9QXW4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as an actin bundling protein.|||Belongs to the fascin family.|||Expressed in testis.|||cytoskeleton http://togogenome.org/gene/10090:Or5aq1 ^@ http://purl.uniprot.org/uniprot/Q8VG38 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Camk2g ^@ http://purl.uniprot.org/uniprot/Q6ZWS7|||http://purl.uniprot.org/uniprot/Q8BW40|||http://purl.uniprot.org/uniprot/Q923T9 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.|||Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state (By similarity).|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (By similarity).|||Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (By similarity). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (By similarity). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning (PubMed:30184290). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023).|||Sarcoplasmic reticulum membrane|||The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization. http://togogenome.org/gene/10090:Fv1 ^@ http://purl.uniprot.org/uniprot/P70213 ^@ Function ^@ Retroviral restriction factor that prevents infection by gammaretroviruses. Acts by interacting with the capsid protein ca after entry of the virus into the cell. This interaction presumably disrupt the capsid thereby inactivating the viral genome, making it unable to enter host nucleus and integrate into host genome. http://togogenome.org/gene/10090:Defb30 ^@ http://purl.uniprot.org/uniprot/Q30KN4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Sash3 ^@ http://purl.uniprot.org/uniprot/Q8K352 ^@ Function|||Tissue Specificity ^@ May function as a signaling adapter protein in lymphocytes.|||Preferentially expressed in lymphoid tissues. Expressed in bone marrow, thymus, spleen, lymph nodes and Peyer patches of gut. In the spleen and lymph nodes, expressed in both T- and B-cells. In the thymus, in the medulla and cortex. http://togogenome.org/gene/10090:Slc28a1 ^@ http://purl.uniprot.org/uniprot/E9PXX9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.|||Cell membrane|||Due to its high apparent affinity but slow transport, adenosine could act as a negative regulator of pyrimidine transport under some conditions.|||N-glycosylated. N-glycosylation is required for localization to the plasma membrane and the transporter activity.|||Sodium and pyrimidine nucleoside symporter of the plasma membrane that imports uridine, thymidine and cytidine into cells by coupling their transport to the transmembrane sodium electrochemical gradient. Also transports adenosine, an atypical substrate transported with high apparent affinity, but low maximum velocity. Therefore, exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit). Involved in renal nucleoside (re)absorption. http://togogenome.org/gene/10090:Aldh1l2 ^@ http://purl.uniprot.org/uniprot/Q8K009 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Homozygous knockout mice lacking Aldh1l2 are viable and fertile and no embryonic lethality is observed (PubMed:33168096). They do not display phenotypic differences in terms of growth, food consumption and development (PubMed:33168096). 10-formyl-THF and dihydrofolate accumulate in the liver of the knockout mice. It is associated with a decrease in levels of NADPH and ATP specifically in the mitochondrion (PubMed:33168096). Male knockout mice accumulate more fats in the liver which is associated with impaired beta-oxidation of fatty acids (PubMed:33168096).|||In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.|||In the N-terminal section; belongs to the GART family.|||Mitochondrial 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide.|||Mitochondrion|||Phosphopantetheinylation at Ser-375 by AASDHPPT is required for the formyltetrahydrofolate dehydrogenase activity.|||The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity. It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2.|||The N-terminal hydrolase domain has an NADP-independent formyltetrahydrofolate hydrolase activity, releasing formate and tetrahydrofolate.|||The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2. The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2. http://togogenome.org/gene/10090:Cyp11a1 ^@ http://purl.uniprot.org/uniprot/Q9QZ82 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).|||Belongs to the cytochrome P450 family.|||Interacts with FDX1/adrenodoxin.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or4e5 ^@ http://purl.uniprot.org/uniprot/Q0VEP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnf43 ^@ http://purl.uniprot.org/uniprot/A3KMI3|||http://purl.uniprot.org/uniprot/Q5NCP0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 14.5 dpc, in the developing limb, expressed only in the ectoderm and, in developing lungs, detected in the epithelium.|||Autoubiquitinated.|||Belongs to the ZNRF3 family.|||Cell membrane|||Conditional knockout mice lacking both Rnf43 and Znrf3 in intestine show a marked expansion of the proliferative compartment, resembling the effects of acute deletion of Apc.|||E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (PubMed:22895187). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (By similarity).|||Endoplasmic reticulum membrane|||Expressed in crypt base columnar cells of small intestinal epithelium. Crypt base columnar cells are small cycling cells residing between the terminally differentiated Paneth cells at crypt bottoms. Colocalizes with Lgr5-positive stem cells.|||Interacts with AKAP8L, NONO and SFPQ. Interacts with FZD5 (By similarity). Identified in a complex composed of RNF43, LGR5 and RSPO1 (By similarity). Interacts with RSPO2 (By similarity). Interacts with LMBR1L (PubMed:31073040).|||Nucleus envelope http://togogenome.org/gene/10090:Coa7 ^@ http://purl.uniprot.org/uniprot/Q921H9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the hcp beta-lactamase family.|||Interacts with CHCHD4/MIA40 through transient intermolecular disulfide bonds.|||Mitochondrion intermembrane space|||Required for assembly of mitochondrial respiratory chain complex I and complex IV. http://togogenome.org/gene/10090:Birc3 ^@ http://purl.uniprot.org/uniprot/A2CGA5|||http://purl.uniprot.org/uniprot/O08863|||http://purl.uniprot.org/uniprot/Q3TSE5 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.|||Belongs to the IAP family.|||Cytoplasm|||Interacts with PRSS25; the interaction inhibits apoptotic suppressor activity. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2). Interaction with TRAF2 is required for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with RIP1, RIP2, RIP3, RIP4 and USP19 (By similarity).|||Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8.|||Nucleus|||USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination. http://togogenome.org/gene/10090:Racgap1 ^@ http://purl.uniprot.org/uniprot/Q9WVM1 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 6.5 dpc expressed in primitive endoderm, embryonic ectoderm, extraembryonic ectoderm and the ectoplacental cone. By 7.5 dpc, a widespread expression was observed in all intra- and extraembryonic tissues and also in the giant cells lining the inner boundary of the deciduum. At 9.5 dpc, expression was elevated in the neuroepithelium of the brain ventricles and the neural tube. By 12.5 dpc, expression remains widespread and in the brain higher levels were observed in the ventricular zone of the two telencephalic lobes, and in the mesencephalon and diencephalon, with the exception of the median sulcus. In adult brain, highest levels of expression were detected in cerebellum, specifically the Purkinje cell layer extending into the molecular layer.|||Cell membrane|||Cleavage furrow|||Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Has a critical role in erythropoiesis (By similarity). Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells.|||Cytoplasm|||Expression is down-regulated during macrophage differentiation of M1 cells.|||Heterotetramer of two molecules each of RACGAP1 and KIF23. Found in the centralspindlin complex. Associates with alpha-, beta- and gamma-tubulin and microtubules. Interacts via its Rho-GAP domain with RND2. Associates with AURKB during M phase. Interacts via its Rho-GAP domain and basic region with PRC1. The interaction with PRC1 inhibits its GAP activity towards CDC42 in vitro, which may be required for maintaining normal spindle morphology. Interacts with SLC26A8 via its N-terminus. Interacts with RAB11FIP3. Interacts with ECT2; the interaction is direct, occurs at anaphase and during cytokinesis in a microtubule-dependent manner, is enhanced by phosphorylation by PLK1 and phosphorylation at Ser-165 plays a major role in mediating binding. Interacts with KIF23; the interaction is direct.|||Highly expressed in testis, thymus and spleen and weakly expressed in brain, heart, skeletal muscle and kidney. In testis, expression is restricted to germ cells with the highest levels of expression found in spermatocytes. Not detected in adult liver. Also expressed in fetal liver and in several hematopoietic cell lines.|||Midbody ring|||Nucleus|||Phosphorylated at multiple sites in the midbody during cytokinesis (By similarity). Phosphorylation by AURKB on Ser-388 at the midbody is, at least in part, responsible for exerting its latent GAP activity towards RhoA (By similarity). Phosphorylation on multiple serine residues by PLK1 enhances its association with ECT2 and is critical for cleavage furrow formation (By similarity). Phosphorylation on Ser-165 plays a major role in mediating interaction with ECT2 (By similarity). Phosphorylation on Ser-158 does not appear to contribute to binding to ECT2 (By similarity).|||The coiled coil region is indispensible for localization to the midbody during cytokinesis.|||The phorbol-ester/DAG-type zinc finger domain mediates interaction with membranes enriched in phosphatidylinositol 3,4,5-trisphosphate and is required during mitotic cytokinesis for normal attachment of the midbody to the cell membrane.|||acrosome|||spindle http://togogenome.org/gene/10090:Gnai1 ^@ http://purl.uniprot.org/uniprot/B2RSH2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-alpha family. G(i/o/t/z) subfamily.|||Cell membrane|||Cytoplasm|||Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (By similarity). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis. Required for cortical dynein-dynactin complex recruitment during metaphase (By similarity).|||Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG1. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG2. GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins (By similarity). Interacts (GDP-bound form) with GPSM1; this inhibits guanine nucleotide exchange and GTP binding (By similarity). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains); this inhibits guanine nucleotide exchange. Interacts with RGS10; this strongly enhances GTP hydrolysis. Interacts with RGS1 and RGS16; this strongly enhances GTPase activity. Interacts with RGS4. Interacts with RGS12. Interacts (via active GTP- or inactive GDP-bound forms) with RGS14 (via RGS and GoLoco domains). Interacts with RGS3, RGS6, RGS7, RGS8, RGS17, RGS18 and RGS20 (in vitro) (By similarity). Interacts (GDP-bound form) with RIC8A (via C-terminus) (By similarity). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif); the interaction leads to activation of GNAI1 (By similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of GNAI1 (By similarity). Interacts (inactive GDP-bound form) with CCDC8A/GIV (via GBA motif) (By similarity).|||Membrane|||Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation.|||Nucleus|||Palmitoylation at Cys-3 varies with membrane lipid composition.|||cell cortex|||centrosome http://togogenome.org/gene/10090:Irgc1 ^@ http://purl.uniprot.org/uniprot/D3Z720 ^@ Similarity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family. http://togogenome.org/gene/10090:Sult2a8 ^@ http://purl.uniprot.org/uniprot/Q8BGL3 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family.|||Down-regulated by PPARA agonist Wy-14.643.|||Hepatic sulfotransferase involved in the maintenance of bile acid homeostasis and energy balance. Catalyzes the transfer of sulfonate group from 3'-phosphoadenylyl sulfate (PAPS) to the 7-alpha hydroxy group of primary bile acids to form 7-monosulfate derivatives in the pathway of bile acid elimination. Displays high catalytic efficiency toward cholate, chenodeoxycholate and their glycine and taurine conjugates.|||Liver (at protein level).|||Not detected in 8.5 and 14.5 dpc embryos. Expressed early in postnatal liver reaching maximal levels at one month of age in both male and female mice. The expression in female mice is lower than in males across the lifespan.|||The short isoform L-STL2 appears to be a minor form. It is likely non-functional as it lacks a conserved C-terminus region required for PAPS binding and sulfotransferase activity.|||cytosol http://togogenome.org/gene/10090:Il1f10 ^@ http://purl.uniprot.org/uniprot/Q3KNF2|||http://purl.uniprot.org/uniprot/Q8R459 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-1 family.|||Cytokine with immunomodulatory activity. Alone, does not induce cytokine production, but reduces IL22 and IL17A production by T-cells in response to heat-killed Candida albicans. Reduces IL36G-induced production of IL8 by peripheral blood mononuclear cells. Increases IL6 production by dendritic cells stimulated by bacterial lipopolysaccharides (LPS). Ligand for IL-36R/IL1RL2 (By similarity).|||Cytoplasm|||Endoplasmic reticulum-Golgi intermediate compartment|||Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||Secreted http://togogenome.org/gene/10090:Or6d13 ^@ http://purl.uniprot.org/uniprot/Q7TS32 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Dmwd ^@ http://purl.uniprot.org/uniprot/Q08274 ^@ Caution|||Developmental Stage|||Subcellular Location Annotation|||Tissue Specificity ^@ In brain, shows increasing expression levels from postnatal day 7 onwards reaching peak levels by postnatal day 21 (at protein level) (PubMed:12691844). Expression is seen very early in embryogenesis, 9.5 dpc in all parts of the embryo (PubMed:7633444). Mid-gestation embryos (14.5 dpc) show high expression in all neural tissues such as telencephalon, retina and spinal cord (PubMed:7633444). In the 16.5 day old embryo high expression is seen in the neural tissues, like telencephalon and mesencephalon and in the non-neural tissues, such as muscle tissues in the tongue and around the ribs (PubMed:7633444).|||It is uncertain whether Met-1 or Met-16 is the initiator.|||Nucleus|||Perikaryon|||Widely expressed in brain where it localizes to the olfactory bulb, forebrain, thalamus, hippocampus, cerebellum, cortex and hypothalamus (at protein level) (PubMed:12691844). Expression seems to be particularly strong in areas of high synaptic density such as the glomerular layer of the olfactory bulb, and mossy fiber terminal fields of the hippocampus (at protein level) (PubMed:12691844). Expressed in retina, with strongest expression in the external and internal plexiform layers (at protein level) (PubMed:12691844). Strongly expressed in brain and testis (PubMed:7633444, PubMed:1302022). Also detected at lower levels in heart, kidney, liver, lung, ovary, uterus, bladder and skeletal muscle (PubMed:7633444, PubMed:1302022). In testis, expression seems to be restricted to secondary spermatocytes (PubMed:1302022).|||dendrite http://togogenome.org/gene/10090:Scap ^@ http://purl.uniprot.org/uniprot/Q6GQT6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat SCAP family.|||COPII-coated vesicle membrane|||Cholesterol bound to SSD domain of SCAP or oxysterol bound to INSIG (INSIG1 or INSIG2) leads to masking of an ER export signal (also named MELADL motif) on SCAP possibly by moving the signal further away from the ER membrane.|||Endoplasmic reticulum membrane|||Escort protein required for cholesterol as well as lipid homeostasis (PubMed:11358865, PubMed:9854040). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:11358865, PubMed:9854040, PubMed:29068315). At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (By similarity). Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity). Binds cholesterol via its SSD domain (By similarity).|||Golgi apparatus membrane|||Loop-1 binds to loop-7, enabling interaction with COPII-coated vesicles. When levels of cholesterol in the endoplasmic reticulum increase, Loop-1 binds to cholesterol instead, thereby disrupting direct binding between the two loops and preventing the SCAP-SREBP complex from exiting the endoplasmic reticulum.|||Membrane region forms a homotetramer. Component of the SCAP-SREBP complex (composed of SCAP and SREBF1/SREBP1 or SREBF2/SREBP2); interacts with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal cytoplasmic domain. Forms a ternary complex with INSIG1 or INSIG2 through its transmembrane domains at high sterol concentrations. Interacts with the SEC23-SEC24 complex in a SAR1-GTP-dependent manner through an ER export signal in its third cytoplasmic loop (By similarity). Interacts with RNF139; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP-SREBP complex. Interacts with SPRING1 (By similarity).|||Mice lacking Scap in their liver show an 80% reduction in cholesterol and fatty acid synthesis in the liver as well as a lack of regulation of target gene expression in response to cholesterol deprivation or insulin elevation. Mice expressing dominant negative mutant Scap in their liver show higher levels of mature Srebf1 and Srebf2 as well as transcripts encoding proteins involved in uptake and synthesis of cholesterol and fatty acids. They show an 1.6-fold increase in liver size as well as a six-fold increase in cholesterol and a nine-fold increase in triglyceride content of the liver. Their plasma levels of cholesterol and triglycerides are reduced by 50%. They show reduced down-regulation of mature Srebf1/2 when fed a high cholesterol diet.|||Ubiquitinated at Lys-454 and Lys-466. RNF145 triggers ubiquitination of SCAP, likely inhibiting SCAP-SREBP complex transport to the Golgi apparatus and the subsequent processing/maturation of SREBF2/SREBP2. http://togogenome.org/gene/10090:Megf11 ^@ http://purl.uniprot.org/uniprot/E9Q918|||http://purl.uniprot.org/uniprot/Q80T91 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the MEGF family.|||Cell membrane|||Homomer. Does not interact with MEGF10.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May regulate the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements. http://togogenome.org/gene/10090:Dock10 ^@ http://purl.uniprot.org/uniprot/Q8BZN6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 'Zizim' means 'spike' in Hebrew.|||At early postnatal stages, expressed broadly in the cerebellum and from P15 the expression becomes restricted to Purkinje cells.|||Belongs to the DOCK family.|||Cytoplasm|||Expressed in brain, lung, spleen, mesenteric lymph nodes (MLN) and thymus (PubMed:15710388, PubMed:25729399). Expressed by B and T splenocytes (PubMed:21514340). In brain, expressed by Purkinje cells during postnatal development and hippocampal neurons (PubMed:25851601).|||Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway (PubMed:25851601). Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression (PubMed:27502165).|||Isoform 4: Highly induced by IL4 in B splenocytes, but not T splenocytes.|||Knockout mice are viable and fertile (PubMed:25729399, PubMed:27502165). They show decreased numbers of B-cells in spleen, both follicular B-cells and marginal zone B-cells, and in peripheral blood, but not in bone marrow (PubMed:25729399, PubMed:27502165). Their percentage of splenic CD8(+) T-cells is decreased comparing to wild types (PubMed:25729399).|||Nucleus|||The DOCKER domain may mediate some GEF activity.|||dendritic spine http://togogenome.org/gene/10090:Thoc2l ^@ http://purl.uniprot.org/uniprot/E9Q5E2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the THOC2 family.|||Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with THOC1, POLDIP3 and ZC3H11A.|||Nucleus http://togogenome.org/gene/10090:Spcs1 ^@ http://purl.uniprot.org/uniprot/Q9D958 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SPCS1 family.|||Component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (By similarity). Dispensable for SPC enzymatic activity (By similarity).|||Component of the signal peptidase complex paralog A (SPC-A) composed of a catalytic subunit SEC11A and three accessory subunits SPCS1, SPCS2 and SPCS3. Component of the signal peptidase complex paralog C (SPC-C) composed of a catalytic subunit SEC11C and three accessory subunits SPCS1, SPCS2 and SPCS3. Within the complex, interacts with SPCS2 and SPCS3. The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids.|||Endoplasmic reticulum membrane|||It is uncertain whether Met-1 or Met-60 is the initiator.|||May be phosphorylated. http://togogenome.org/gene/10090:Trmt1l ^@ http://purl.uniprot.org/uniprot/A0A0R4J0U8|||http://purl.uniprot.org/uniprot/A2RSY6 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.|||Expressed in various neuronal structures during embryonic development, including spinal ganglia, trigeminal nerve and ganglion, olfactory and nasopharyngeal epithelium, nuclei of the metencephalon, thalamus and medulla oblongata. Also expressed in lung, esophagus, epiglottis, ependyma, vertebral column, spinal cord and brown adipose tissue. Expression persists in the adult brain with dynamically changing patterns in cortex and cerebellum.|||May play a role in motor coordination and exploratory behavior.|||Mice are viable and show no apparent anatomical defects. However, they display significantly altered motor coordination and aberrant exploratory behavior. http://togogenome.org/gene/10090:Slc2a4 ^@ http://purl.uniprot.org/uniprot/P14142 ^@ Disease Annotation|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.|||Binds to DAXX (By similarity). Interacts via its N-terminus with SRFBP1 (By similarity). Interacts with NDUFA9 (By similarity). Interacts with TRARG1; the interaction is required for proper SLC2A4 recycling after insulin stimulation (PubMed:26629404).|||Cell membrane|||Defects in Slc2a4 may be the cause of certain post-receptor defects in non-insulin-dependent diabetes mellitus (NIDDM).|||Endomembrane system|||Expressed in skeletal and cardiac muscles (PubMed:2654938, PubMed:26240143). Expressed in brown and white adipose tissues (PubMed:2654938, PubMed:26240143).|||Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation (PubMed:26240143, PubMed:26629404). Response to insulin is regulated by its intracellular localization: in the absence of insulin, it is efficiently retained intracellularly within storage compartments in muscle and fat cells (PubMed:26240143, PubMed:26629404). Upon insulin stimulation, translocates from these compartments to the cell surface where it transports glucose from the extracellular milieu into the cell (PubMed:26240143, PubMed:26629404).|||Insulin-stimulated phosphorylation of TBC1D4 is required for GLUT4 translocation.|||Palmitoylated. Palmitoylation by ZDHHC7 controls the insulin-dependent translocation of GLUT4 to the plasma membrane.|||Sumoylated.|||The dileucine internalization motif is critical for intracellular sequestration.|||perinuclear region http://togogenome.org/gene/10090:Fgf5 ^@ http://purl.uniprot.org/uniprot/A0A7U3L698|||http://purl.uniprot.org/uniprot/P15656 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heparin-binding growth factors family.|||Interacts with FGFR1 and FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase (By similarity).|||Secreted|||Seems to have an antagonistic effect compared to that of the isoform Long. http://togogenome.org/gene/10090:Or51af1 ^@ http://purl.uniprot.org/uniprot/E9Q4X7 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gng13 ^@ http://purl.uniprot.org/uniprot/Q9JMF3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G protein gamma family.|||Cell membrane|||G proteins are composed of 3 units, alpha, beta and gamma.|||Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. http://togogenome.org/gene/10090:Nxph3 ^@ http://purl.uniprot.org/uniprot/Q544G3|||http://purl.uniprot.org/uniprot/Q91VX5 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the neurexophilin family.|||Highest level in brain, present also in lung, kidney and testis.|||May be proteolytically processed at the boundary between the N-terminal non-conserved and the central conserved domain in neuron-like cells.|||May be signaling molecules that resemble neuropeptides.|||May be signaling molecules that resemble neuropeptides. Ligand for alpha-neurexins.|||Secreted http://togogenome.org/gene/10090:Uggt1 ^@ http://purl.uniprot.org/uniprot/Q6P5E4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 8 family.|||Endoplasmic reticulum lumen|||Endoplasmic reticulum-Golgi intermediate compartment|||Monomer as well as in a tight complex with SELENOF (PubMed:11278576). Interacts with METTL23 (By similarity). Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX (By similarity).|||Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic reticulum. Reglucosylated proteins are recognized by calreticulin for recycling to the endoplasmic reticulum and refolding or degradation (By similarity).|||The N-terminal non-catalytic domain is assumed to mediate recognition of proteins with partial folding defects. http://togogenome.org/gene/10090:Fmr1nb ^@ http://purl.uniprot.org/uniprot/Q80ZA7 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fam149b ^@ http://purl.uniprot.org/uniprot/Q6NSV7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FAM149 family.|||Interacts with TBC1D32; may play a role in cilium assembly.|||Involved in the localization of proteins to the cilium and cilium assembly. Indirectly regulates the signaling functions of the cilium, being required for normal SHH/smoothened signaling and proper development.|||Strong expression in the early embryonic stages 8 dpc, 9 dpc and 10 dpc in the neuroepithelium and by the maxillary arches.|||cilium http://togogenome.org/gene/10090:Nek3 ^@ http://purl.uniprot.org/uniprot/Q9R0A5 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Brain.|||Cytoplasm|||Highly expressed during embryogenesis and early postnatal life, but is expressed at lower levels in adults.|||Interacts with PXN, PRLR, VAV1 and VAV2 and this interaction is prolactin-dependent.|||Phosphorylation at Thr-477 regulates its catalytic activity.|||Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2.|||axon http://togogenome.org/gene/10090:Usp39 ^@ http://purl.uniprot.org/uniprot/Q3TIX9 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C19 family.|||Deubiquitinating enzyme that plays a role in many cellular processes including cellular antiviral response, epithelial morphogenesis, DNA repair or B-cell development (PubMed:35139388, PubMed:35440748, PubMed:36651806). Plays a role in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the precatalytic spliceosome (By similarity). Specifically regulates immunoglobulin gene rearrangement in a spliceosome-dependent manner, which involves modulating chromatin interactions at the Igh locus and therefore plays an essential role in B-cell development (By similarity). Regulates AURKB mRNA levels, and thereby plays a role in cytokinesis and in the spindle checkpoint. Regulates apoptosis and G2/M cell cycle checkpoint in response to DNA damage by deubiquitinating and stabilizing CHK2. Plays also an important role in DNA repair by controlling the recruitment of XRCC4/LIG4 to DNA double-strand breaks for non-homologous end-joining repair. Participates in antiviral activity by affecting the type I IFN signaling by stabilizing STAT1 and decreasing its 'Lys-6'-linked ubiquitination (By similarity). Contributes to non-canonical Wnt signaling during epidermal differentiation (By similarity). Acts as a negative regulator NF-kappa-B activation through deubiquitination of 'Lys-48'-linked ubiquitination of NFKBIA (By similarity).|||Lacks the conserved His and Cys residues that are essential for the activity of de-ubiquitinating enzymes. Lacks ubiquitin C-terminal hydrolase activity.|||Nucleus|||The U4/U6-U5 tri-snRNP complex is a building block of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8.|||USP39-deficient embryos display early embryonic lethality due to a failure in primitive streak formation and apico-basal polarity in epiblast cells (PubMed:35440748). In addition, USP39-deficient mice are more sensitive to LPS stimulation and bacterial infection (PubMed:36651806). http://togogenome.org/gene/10090:Agbl3 ^@ http://purl.uniprot.org/uniprot/Q8CDP0 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ AGBL2 and AGBL3 double knockout mutant mice are viable and display no obvious phenotypic alterations. Show an increase in tubulin and MYLK polyglutamylation in sperm.|||Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins (PubMed:25103237). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein (PubMed:25103237). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:25103237). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK (PubMed:25103237). May catalyze the hydrolysis of aspartate from the carboxy-terminus of target proteins (PubMed:25103237). Does not show detyrosinase or deglycylase activities from the carboxy-terminus of target proteins (PubMed:25103237).|||Up-regulated during ciliogenesis.|||Widely expressed. Expressed abundantly in tissues with m otile cilia such as testis, lung and trachea. Abundantly expressed in pituitary and kidney, moderately expressed in brain, eye, fat, pancreas, stomach, and adrenal.|||cytosol http://togogenome.org/gene/10090:Retnla ^@ http://purl.uniprot.org/uniprot/G3X8W2|||http://purl.uniprot.org/uniprot/Q8JZM3|||http://purl.uniprot.org/uniprot/Q9EP95 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the resistin/FIZZ family.|||Highest levels in adipose tissue.|||Monomer.|||Probable hormone. Plays a role in pulmonary vascular remodeling.|||Secreted http://togogenome.org/gene/10090:Ear1 ^@ http://purl.uniprot.org/uniprot/P97426|||http://purl.uniprot.org/uniprot/Q53ZF0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the pancreatic ribonuclease family.|||Cytoplasmic granule|||Cytotoxin and helminthotoxin with ribonuclease activity. Possesses a wide variety of biological activities (By similarity). http://togogenome.org/gene/10090:Ddi1 ^@ http://purl.uniprot.org/uniprot/Q9DAF3 ^@ Function|||Similarity ^@ Belongs to the DDI1 family.|||Probable aspartic protease (By similarity). Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2. Required, with DDI2, for cellular survival following replication stress. Together or redudantly with DDI2, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity (By similarity). http://togogenome.org/gene/10090:Dctd ^@ http://purl.uniprot.org/uniprot/G3X908|||http://purl.uniprot.org/uniprot/Q8K2D6 ^@ Activity Regulation|||Function|||Similarity|||Subunit ^@ Allosteric enzyme whose activity is greatly influenced by the end products of its metabolic pathway, dCTP and dTTP.|||Belongs to the cytidine and deoxycytidylate deaminase family.|||Homohexamer.|||Supplies the nucleotide substrate for thymidylate synthetase. http://togogenome.org/gene/10090:Fdx2 ^@ http://purl.uniprot.org/uniprot/Q9CPW2 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the adrenodoxin/putidaredoxin family.|||Binds 1 [2Fe-2S] cluster.|||Component of the mitochondrial core iron-sulfur cluster (ISC) complex composed of NFS1, LYRM4, NDUFAB1, ISCU, FXN, and FDX2; this complex is an heterohexamer containing two copies of each monomer. Form an heterodimer complex with NFS1. Interacts (in both their reduced and oxidized states) with the cysteine desulfurase (NFS1:LYRM4) complex; this interaction stimulates cysteine desulfurase activity, and serves as a reductant for Fe-S cluster assembly.|||Electron donor, of the core iron-sulfur cluster (ISC) assembly complex, that acts to reduce the persulfide into sulfide during [2Fe-2S] clusters assembly on the scaffolding protein ISCU (By similarity). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity).|||Mitochondrion|||Mitochondrion matrix http://togogenome.org/gene/10090:Brms1l ^@ http://purl.uniprot.org/uniprot/Q3U1T3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BRMS1 family.|||Component of the Sin3/HDAC1 corepressor complex at least composed of BRMS1, BRMS1L and ING2/ING1L. Interacts with HDAC and SIN3A (By similarity).|||Involved in the histone deacetylase (HDAC1)-dependent transcriptional repression activity. When overexpressed in lung cancer cell line that lacks p53/TP53 expression, inhibits cell growth (By similarity).|||Nucleus http://togogenome.org/gene/10090:Cfap70 ^@ http://purl.uniprot.org/uniprot/D3YVL2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Axoneme-binding protein that plays a role in the regulation of ciliary motility and cilium length.|||Belongs to the CFAP70 family.|||Detected in ependyma, trachea, lung, testis, and oviduct, but not in whole brain, liver, kidney, and spleen (PubMed:30158508). Localizes on the epithelial cilia and sperm flagella (at protein level) (PubMed:30158508).|||The conserved TPR domains are dispensable for ciliary targeting. The N-terminal half is important for cilary localization and/or binding to the axoneme.|||cilium|||cilium axoneme|||flagellum|||flagellum basal body http://togogenome.org/gene/10090:Slc37a2 ^@ http://purl.uniprot.org/uniprot/Q9WU81 ^@ Activity Regulation|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.|||Endoplasmic reticulum membrane|||Highly expressed in bone marrow derived macrophages, and weakly in spleen.|||Inhibited by vanadate but not by chlorogenic acid.|||Inorganic phosphate and glucose-6-phosphate antiporter. May transport cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocate inorganic phosphate into the opposite direction. Independent of a lumenal glucose-6-phosphatase. May not play a role in homeostatic regulation of blood glucose levels.|||Up-regulated by cAMP in macrophages. http://togogenome.org/gene/10090:Ptprcap ^@ http://purl.uniprot.org/uniprot/Q542J3|||http://purl.uniprot.org/uniprot/Q64697 ^@ PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with CD45/PTPRC.|||Leukocyte-specific. Expressed in B- and T-cell lines, in spleen, thymus, and bone marrow of adult mice, and in embryos.|||Membrane|||Phosphorylated on tyrosine residues. http://togogenome.org/gene/10090:Taf3 ^@ http://purl.uniprot.org/uniprot/Q5HZG4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TAF3 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (By similarity). Interacts with TAF10 via histone fold (PubMed:11438666). Interacts with TAF13, TBP, SAP130 and GCN5L2 (By similarity). Interacts with TBPL2 (PubMed:17704303).|||Nucleus|||The PHD-type zinc finger mediates binding to histone H3 methyllysine at position 4 (H3K4me3).|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (By similarity). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (By similarity). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (By similarity). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (By similarity). TAF3 forms the TFIID-A module together with TAF5 and TBP (By similarity). Required in complex with TBPL2 for the differentiation of myoblasts into myocytes (PubMed:17704303). The TAF3-TBPL2 complex replaces TFIID at specific promoters at an early stage in the differentiation process (PubMed:17704303). http://togogenome.org/gene/10090:Defa2 ^@ http://purl.uniprot.org/uniprot/Q8C1N9|||http://purl.uniprot.org/uniprot/Q8C1P0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||Secreted http://togogenome.org/gene/10090:Parp14 ^@ http://purl.uniprot.org/uniprot/Q2EMV9 ^@ Caution|||Function|||Induction|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate residues on target proteins (PubMed:27796300). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (By similarity). Catalyzes mono-ADP-ribosylating STAT1 at 'Glu-657' and 'Glu-705' and thus decreasing STAT1 phosphorylation, negatively regulates pro-inflammatory cytokines production in macrophages in response to IFNG stimulation (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of STAT1 phosphorylation has been called into question and it has been suggested that the inhibition of phosphorylation may be the result of sumoylation of STAT1 'Lys-703' (PubMed:29858569). Mono-ADP-ribosylates STAT6; enhancing STAT6-dependent transcription (PubMed:27796300). In macrophages, positively regulates MRC1 expression in response to IL4 stimulation by promoting STAT6 phosphorylation (PubMed:27796300). Mono-ADP-ribosylates PARP9 (By similarity).|||Auto-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||Interacts with STAT6 (PubMed:16537510). Interacts with PARP10 (By similarity). Interacts with PARP9 in IFNG-stimulated macrophages; the interaction prevents PARP14-mediated STAT1 and STAT6 ADP-riboslylation (By similarity).|||Nucleus|||The role of PARP14-mediated ADP-ribosylation of STAT1 in the prevention of STAT1 phosphorylation has been called into question and it has been suggested that the inhibition of phosphorylation may be the result of sumoylation of STAT1 'Lys-703'.|||Up-regulated by IFNG in macrophages. Down-regulated by IL4 in macrophages.|||Weakly expressed in the thymus during development and in adulthood (PubMed:18069692). Expressed in macrophages (PubMed:27796300). http://togogenome.org/gene/10090:Or6n2 ^@ http://purl.uniprot.org/uniprot/E9Q5F1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Hacd1 ^@ http://purl.uniprot.org/uniprot/A2AQ81|||http://purl.uniprot.org/uniprot/B9EHK9|||http://purl.uniprot.org/uniprot/Q3V4A5|||http://purl.uniprot.org/uniprot/Q9QY80 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the very long-chain fatty acids dehydratase HACD family.|||Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates to the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.|||Differentially expressed during embryogenesis. First detected throughout the somites at 8.5 dpc and in the myotome at 11.5 dpc. Expression was observed in muscles ventral to the developing vertebral column of the neck, thorax, abdomen and tail. Expression was maintained in skeletal muscle types well after the terminal differentiation of muscle fibers. During cardiac development, expression was restricted to the myocytes of the primitive heart tube, and by 10.5 dpc, it was expressed in the muscles throughout all the cardiac chambers. At this last stage it is also detected in the hepatic primordia, and later in embryonic liver. By 15.5 expression was also observed in the smooth muscle surrounding the digestive, respiratory and urogenital tracts.|||Endoplasmic reticulum membrane|||Expressed at high levels in heart, skeletal muscle and testis, weak expression in kidney and liver.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex.|||Membrane|||N-glycosylated.|||Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity. http://togogenome.org/gene/10090:Pramel32 ^@ http://purl.uniprot.org/uniprot/Q3UX49 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Igsf8 ^@ http://purl.uniprot.org/uniprot/Q8R366 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed at 9.5 dpc in the ventral domain of the neural tube, with dorsal expression apparent at 10.5 dpc, as well as in the dorsal bud of the pancreas. Detected at 11.5 dpc within the ventricular zone of the neural tube in the hindbrain, diencephalon and telencephalon; also detected in the epithelial lining of the bronchi and esophagus. At 12.5 dpc, expressed in the bronchi, in the atrial and ventricular myocardium, the dorsal root ganglia and the epithelial lining of the rectum and bladder. At 15.5 dpc, detected in the developing choroid plexus epithelium, neural retina, olfactory epithelium and developing vomeronasal organ.|||Expressed in lymphocytes as well as in many tissues with higher expression in brain. Detected in all regions of the brain with weak expression in the pituitary. Expressed selectively by neurons but not by glial cells. Expressed in myoblasts (at protein level).|||Induced by neurite outgrowth in neuroblastoma cell lines Neuro-2a.|||Interacts directly with CD82 and CD9/tetraspanin-29. Also interacts with integrin alpha-3/beta-1 and integrin alpha-4/beta-1 (By similarity). Part of a complex composed of CD9, PTGFRN and CD81 (PubMed:23575678). Interacts with CD81/tetraspanin-28.|||May play a key role in diverse functions ascribed to CD81 and CD9 such as oocytes fertilization or hepatitis C virus function. May regulate proliferation and differentiation of keratinocytes. May be a negative regulator of cell motility: suppresses T-cell mobility coordinately with CD81, associates with CD82 to suppress prostate cancer cell migration, regulates epidermoid cell reaggregation and motility on laminin-5 with CD9 and CD81 as key linkers. May also play a role on integrin-dependent morphology and motility functions. May participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain.|||The Ig-like C2-type domains 3 and 4 are required for interaction with CD81.|||The short cytoplasmic domain is very basic, interacts with membrane PIPs, and mediates plasma membrane localization. http://togogenome.org/gene/10090:Gabrr1 ^@ http://purl.uniprot.org/uniprot/P56475 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRR1 sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA receptor could play a role in retinal neurotransmission (By similarity).|||Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1 (By similarity).|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Acaa2 ^@ http://purl.uniprot.org/uniprot/Q8BWT1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the thiolase-like superfamily. Thiolase family.|||Homotetramer. Interacts with BNIP3.|||In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA. Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms. Also catalyzes the condensation of two acetyl-CoA molecules into acetoacetyl-CoA and could be involved in the production of ketone bodies. Also displays hydrolase activity on various fatty acyl-CoAs (By similarity). Thereby, could be responsible for the production of acetate in a side reaction to beta-oxidation (By similarity). Abolishes BNIP3-mediated apoptosis and mitochondrial damage (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Rab19 ^@ http://purl.uniprot.org/uniprot/P35294 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Expressed in a tissue-specific manner. Detected at high levels in intestine, lung and spleen, and at a lower level in kidney. http://togogenome.org/gene/10090:Poldip3 ^@ http://purl.uniprot.org/uniprot/Q8BG81 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with POLD2. Interacts with NCBP1 and EIF4A3. Associates with the multiprotein exon junction complex (EJC). Interacts with RPS6KB1 (activated). Interacts with ERH. Interacts with THOC2, DDX39B and ZC3H11A; the interactions are ATP-dependent and indicative for an association with the TREX complex (By similarity).|||Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex (By similarity).|||Nucleus|||Nucleus speckle http://togogenome.org/gene/10090:Gzmg ^@ http://purl.uniprot.org/uniprot/P13366 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytolytic granule|||This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. http://togogenome.org/gene/10090:Or2t1 ^@ http://purl.uniprot.org/uniprot/E9Q3K2|||http://purl.uniprot.org/uniprot/Q62342 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Renbp ^@ http://purl.uniprot.org/uniprot/A0A8Z1S8W2|||http://purl.uniprot.org/uniprot/A0A8Z1SL50|||http://purl.uniprot.org/uniprot/P82343 ^@ Function|||Similarity|||Subunit ^@ Belongs to the N-acylglucosamine 2-epimerase family.|||Catalyzes the interconversion of N-acetylglucosamine to N-acetylmannosamine (PubMed:22692205). Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway (PubMed:22692205).|||Homodimer. Forms a heterodimer with renin and inhibits its activity. http://togogenome.org/gene/10090:Kif14 ^@ http://purl.uniprot.org/uniprot/L0N7N1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Cytoplasm|||Directly interacts with PRC1 within a complex also containing KIF4A, KIF20A and KIF23; targets to the central spindle. Directly interacts with CIT depending on the activation state of the kinase (stronger interaction with the kinase-dead form); targets to the midbody. Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation (By similarity). Interacts with AKT1; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation. Interacts with SVIL; at midbody during cytokinesis. Interacts with RADIL (via PDZ domain); recruits RADIL to the microtubule network restricting RADIL from interaction with activated RAP1A.|||Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (PubMed:24949858). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (By similarity). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (By similarity). Regulates cell growth through regulation of cell cycle progression and cytokinesis. During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (By similarity). During late neurogenesis, regulates the cerebellar and cerebral cortex development and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (PubMed:23308235, PubMed:24931760). Also is required for chromosome congression and alignment during mitotic cell cycle process (By similarity). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (By similarity).|||Midbody|||Nucleus|||The kinesin motor domain binds to microtubules with high affinity and has a robust ATPase activity but a very slow motility. The kinesin motor domain protects microtubules from cold depolymerization. Binds to each tubulin heterodimer resulting in a microtubule complexes. Binds at the tubulin intradimer interface, at the crest of the protofilament, and orients slightly toward the next protofilament.|||The lag homozygous mutant mice that lack detectable Kif14 expression are indistinguishable from normal littermates at birth. At P10, mutants exhibit an overt ataxic phenotype that increased in severity over time. At P12, lag homozygous mutant mice are unable to stand for 10 s on a narrow platform. Their gait is wide and uncoordinated, and they frequently fell on their backs while walking. These defects in voluntary movement control, posture and balance are accompanied by progressive weakness and failure to gain body weight. By P14, the homozygous mutants in a litter could be identified by their small size and uncontrolled movements. The homozygous mutants all died by P21. The lag homozygous mutant mice also display a flathead, a reduction in brain size, slender optic nerves, and a translucent spinal cord.|||spindle http://togogenome.org/gene/10090:Dnaja1 ^@ http://purl.uniprot.org/uniprot/P63037|||http://purl.uniprot.org/uniprot/Q5NTY0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Co-chaperone for HSPA8/Hsc70. Plays a role in protein transport into mitochondria via its role as co-chaperone. Stimulates ATP hydrolysis, but not the folding of unfolded proteins mediated by HSPA1A (in vitro). Promotes apoptosis in response to cellular stress mediated by exposure to anisomycin or UV (By similarity). Functions as co-chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis.|||Cytoplasm|||Identified in a complex with HSPA1B and BAX (PubMed:14752510). Interacts with RNF207 (By similarity).|||Membrane|||Microsome|||Mitochondrion|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Cep120 ^@ http://purl.uniprot.org/uniprot/Q7TSG1 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CEP120 family.|||Expressed in embryonic brain from 10.5 to 17.5 dpc. Expressed in neocortical neural progenitors at the ventrical surface at 12.5 dpc (at protein level). Expressed in brain, heart, lung, liver, kidney, small intestine and limb at 16.5 dpc.|||Interacts with TACC2, TACC3, CCDC52, TALPID3.|||Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (By similarity).|||Ubiquitous. Highly expressed in brain, lung and kidney and weakly expressed in heart, liver, small intestine and limb (at protein level). Expressed in brain.|||centrosome http://togogenome.org/gene/10090:Morc3 ^@ http://purl.uniprot.org/uniprot/F7BJB9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Chromosome|||Dimerization of the ATPase domain is strictly required for the catalytic activity and binding to double-stranded DNA. Disrupting the interface between ATPase and the CW domains releases autoinhibition since the CW domain sterically impedes binding of the ATPase domain to DNA.|||Homodimer. The sumoylated form interacts with PML (via SUMO-interacting motif). Interacts with TP53.|||Lethality occurs at birth or within a day thereafter, for unknown reasons. Embryos at 14.5 dpc are morphologically indistinguishable from wild type (PubMed:17332504). MORC3 deletion leads to increased osteoblast differentiation and altered osteoblastic gene expression through up-regulation of IFN-beta/STAT1 signaling pathway (PubMed:27188231).|||Nuclear matrix protein which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism and plays a role in innate immunity by restricting different viruses through modulation of the IFN response. Mechanistically, possesses a primary antiviral function through a MORC3-regulated element that activates IFNB1, and this function is guarded by a secondary IFN-repressing function. Sumoylated MORC3-NBs associates with PML-NBs and recruits TP53 and SP100, thus regulating TP53 activity (PubMed:17332504). Binds RNA in vitro. Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) 'Lys-4' on histone H3. The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0.|||Nucleus matrix|||PML body|||Sumoylation is involved in interaction with PML and localization to PML nuclear bodies.|||The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3.|||nucleoplasm http://togogenome.org/gene/10090:Fam8a1 ^@ http://purl.uniprot.org/uniprot/Q3URQ4 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Cnga4 ^@ http://purl.uniprot.org/uniprot/Q3UW12 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family. CNGA4 subfamily.|||Calcium-calmodulin exerts its inhibitory effect in cAMP sensitivity by binding to IQ-like motif of CNGA4 and preferably binds to the channel in the closed state. Inhibition by PIP3 of the CNG channel probably occurs via CGNA2 binding (By similarity).|||Heterotetramer composed of two subunits of CNGA2, one of CNGA4 and one of CNGB1b. The complex forms the cyclic nucleotide-gated (CNG) channel of olfactory neurons (By similarity).|||Membrane|||Second messenger, cAMP, causes the opening of cation-selective cyclic nucleotide-gated (CNG) channels and depolarization of the neuron (olfactory sensory neurons, OSNs). CNGA4 is the modulatory subunit of this channel which is known to play a central role in the transduction of odorant signals and subsequent adaptation. By accelerating the calcium-mediated negative feedback in olfactory signaling it allows rapid adaptation to odor stimulation and extends its range of odor detection.|||The C-terminal coiled-coil domain mediates trimerization of CNGA subunits. http://togogenome.org/gene/10090:Or5b24 ^@ http://purl.uniprot.org/uniprot/Q8VEV8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ctbs ^@ http://purl.uniprot.org/uniprot/Q102J0|||http://purl.uniprot.org/uniprot/Q8R242 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 18 family.|||Involved in the degradation of asparagine-linked glycoproteins. Hydrolyze of N-acetyl-beta-D-glucosamine (1-4)N-acetylglucosamine chitobiose core from the reducing end of the bond, it requires prior cleavage by glycosylasparaginase (By similarity).|||Lysosome http://togogenome.org/gene/10090:Rxfp1 ^@ http://purl.uniprot.org/uniprot/Q6R6I7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with C1QTNF8.|||Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP. http://togogenome.org/gene/10090:Asb6 ^@ http://purl.uniprot.org/uniprot/Q91ZU1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ankyrin SOCS box (ASB) family.|||Binds APS. Identified in a complex with ELOB and ELOC. Interacts with CUL5 and RNF7 (By similarity).|||Cytoplasm|||Detected in adipocytes.|||Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes. http://togogenome.org/gene/10090:Casp9 ^@ http://purl.uniprot.org/uniprot/A2AS93|||http://purl.uniprot.org/uniprot/Q8C3Q9 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the peptidase C14A family.|||Cleavages at Asp-353 by granzyme B and at Asp-368 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events (By similarity).|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 35 kDa (p35) and a 10 kDa (p10) subunit. Caspase-9 and APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome C and ATP. Interacts (inactive form) with EFHD2. Interacts with HAX1. Interacts with BIRC2/c-IAP1, XIAP/BIRC4, BIRC5/survivin, BIRC6/bruce and BIRC7/livin. Interacts with ABL1 (via SH3 domain); the interaction is direct and increased in the response of cells to genotoxic stress and ABL1/c-Abl activation (By similarity). Interacts with BCL2L10 (By similarity).|||Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).|||Phosphorylated at Thr-163 by MAPK1/ERK2. Phosphorylation at Thr-163 is sufficient to block caspase-9 processing and subsequent caspase-3 activation (By similarity). Phosphorylation on Tyr-191 by ABL1/c-Abl; occurs in the response of cells to DNA damage (PubMed:15657060). http://togogenome.org/gene/10090:Sirt3 ^@ http://purl.uniprot.org/uniprot/Q4FJK3|||http://purl.uniprot.org/uniprot/Q8R104 ^@ Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sirtuin family. Class I subfamily.|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Decreased muscle endurance under energetically demanding conditions (PubMed:24252090). Decreased Mn-SOD activity in liver, increased mitochondrial superoxide levels and genomic instability upon exposure to ionizing radiations (PubMed:21172655). In vivo ATP levels are reduced by 50 % in organs that normally express high levels of this protein (PubMed:18794531). ATP levels are unchanged in organs that normally express low levels of this protein (PubMed:18794531). Leads to increased mitochondrial protein acetylation (PubMed:18794531). Decreased ceramide accumulation in brain mitochondria (PubMed:26620563).|||Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo.|||Mitochondrion matrix|||NAD-dependent protein deacetylase (PubMed:23835326, PubMed:17923681, PubMed:18794531, PubMed:21172655, PubMed:26620563). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:23835326, PubMed:17923681, PubMed:18794531, PubMed:21172655). Known targets include ACSS1, IDH, GDH, PDHA1, SOD2, LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16790548, PubMed:18794531, PubMed:21172655). Contributes to the regulation of the cellular energy metabolism (PubMed:23835326, PubMed:36804859). Important for regulating tissue-specific ATP levels (PubMed:18794531, PubMed:24252090). In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription (PubMed:23283301). Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation (PubMed:26620563). Regulates hepatic lipogenesis. Uses NAD(+) substrate imported by SLC25A47, triggering downstream activation of PRKAA1/AMPK-alpha signaling cascade that ultimately downregulates sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance.|||NAD-dependent protein deacetylase.|||Sirt3 expression decreases by 50% in skeletal muscle upon fasting.|||Strongly expressed in liver and kidney (PubMed:11056054). Expressed in skeletal muscles (at protein level) (PubMed:23283301, PubMed:23835326). Weakly expressed in lung (PubMed:11056054).|||Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (By similarity). Interacts with NDUFA9, ACSS1, IDH2 and GDH (By similarity). Interacts with PCCA (PubMed:23438705). http://togogenome.org/gene/10090:Ube2v2 ^@ http://purl.uniprot.org/uniprot/Q9D2M8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ubiquitin-conjugating enzyme family.|||Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.|||Heterodimer with UBE2N. Binds CHFR (By similarity). http://togogenome.org/gene/10090:Map4 ^@ http://purl.uniprot.org/uniprot/A0A0G2JDN7|||http://purl.uniprot.org/uniprot/E9PZ43|||http://purl.uniprot.org/uniprot/P27546 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with SEPTIN2; this interaction impedes tubulin-binding. Interacts with TRAF3IP1 (PubMed:26487268). Interacts with KNSTRN (By similarity).|||Non-neuronal microtubule-associated protein. Promotes microtubule assembly.|||Phosphorylated at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1 or MARK2), causing detachment from microtubules, and their disassembly (By similarity). Phosphorylation on Ser-760 negatively regulates MAP4 activity to promote microtubule assembly. Isoform 4 is phosphorylated on Ser-333 and Ser-334 (By similarity).|||Testis, striated and cardiac muscle.|||cytoskeleton|||microtubule organizing center http://togogenome.org/gene/10090:Tmem181a ^@ http://purl.uniprot.org/uniprot/Q3U3W2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Casp7 ^@ http://purl.uniprot.org/uniprot/P97864|||http://purl.uniprot.org/uniprot/Q4FJQ4 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase C14A family.|||Cleavage by different proteases, such as granzyme B (GZMB), caspase-1 (CASP1), caspase-8 (CASP8) or caspase-9 (CASP9) generate the two active subunits (PubMed:18667412, PubMed:22807671, PubMed:35705808, PubMed:31251782). Its involvement in different programmed cell death processes is probably specified by the protease that activates CASP7 (PubMed:35705808). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (PubMed:35705808). Cleaved and activated by CASP1 in response to bacterial infection (PubMed:18667412, PubMed:31251782, PubMed:35705808). Propeptide domains can also be cleaved efficiently by CASP3 (By similarity). Active heterodimers between the small subunit of caspase-7 and the large subunit of CASP3, and vice versa, also occur (By similarity). Also cleaved at the N-terminus at alternative sites by CAPN1, leading to its activation (By similarity).|||During activation, the N-terminal disordered prodomain is removed by cleavage (PubMed:18667412). Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11 (PubMed:18667412). The two large and two small subunits then assemble to form the active CASP7 complex (PubMed:18667412). Can be cleaved and activated by different caspases, depending on the context (PubMed:18667412, PubMed:35705808). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (PubMed:35705808). Cleavage and maturation by CASP1 regulates pyroptosis (PubMed:18667412, PubMed:35705808). Inhibited by XIAP, which directly binds to the active site pocket and obstructs substrate entry (By similarity). Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (By similarity).|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit (By similarity). Interacts with XIAP (via its second BIR domain); inhibiting CASP7 activity (By similarity). Interacts with BIRC6/bruce. Interacts with ATXN3 (short isoform 1) (By similarity). Interacts with HSPA5 (By similarity).|||Highly expressed in heart, lung, liver and kidney. Low levels in spleen, skeletal muscle and testis. No expression in the brain.|||No visible phenotype; on the 129/Svj background, mice are healthy (PubMed:16469926). Mice display impaired lipopolysaccharide (LPS)-induced lymphocyte apoptosis and are markedly protected from LPS-induced lethality (PubMed:19168786). Mice lacking Casp3 and Casp7 on the C57BL/6J background die immediately after birth because of defective heart development (PubMed:16469926).|||Nucleus|||Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its activity (By similarity). Phosphorylation at Ser-30 prevents cleavage and activation by initiator caspase CASP9, while phosphorylation at Ser-239 prevents thiol protease activity by preventing substrate-binding (By similarity).|||The exosite polybasic region mediates non-specific RNA-binding, acting as a bridge for RNA-binding target proteins, such as PARP1. The exosite is also required for interaction with non-RNA-binding proteins, such as Hsp90 co-chaperone PTGES3.|||Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (PubMed:16469926, PubMed:19168786). Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences (PubMed:25231987). Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (PubMed:18667412, PubMed:35705808). Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8 and/or CASP9), mediates execution of apoptosis by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and YY1 (PubMed:16469926). Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins (PubMed:16469926). Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair (PubMed:35705808). Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores (PubMed:22807671, PubMed:35705808). Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores (PubMed:35705808). Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1 (PubMed:22464733). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Cleaves and activates sterol regulatory element binding proteins (SREBPs) (By similarity). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9 (PubMed:25231987).|||cytosol|||extracellular space http://togogenome.org/gene/10090:H2-T22 ^@ http://purl.uniprot.org/uniprot/Q31615|||http://purl.uniprot.org/uniprot/Q9BCZ1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class I family.|||Membrane http://togogenome.org/gene/10090:Flcn ^@ http://purl.uniprot.org/uniprot/Q8QZS3 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the folliculin family.|||Embryonic lethality at 5.5-6.5 dpc, showing defects in the visceral endoderm (PubMed:18974783, PubMed:19850877). Heterozygous knockout mice appear normal at birth but develop kidney cysts and solid tumors as they age, probably caused by activation of the mTOR pathway (PubMed:19850877). Conditional deletion in kidney leads to development of polycystic kidneys and renal neoplasia, caused by activation of the mTOR pathway (PubMed:18182616, PubMed:18974783, PubMed:32612235). Mice lacking Tfeb and Flcn in the kidney do not show any abnormality in the kidney, suggesting that the kidney phenotype observed in Flcn knockout mice is due to constitutive activation of Tfeb (PubMed:32612235). Conditional deletion in heart causes cardiac hypertrophy with deregulated energy homeostasis leading to dilated cardiomyopathy: defects are caused by mTORC1 up-regulation (PubMed:24908670). Conditional deletion in adipose tissue leads to browning of white adipose tissue (WAT) caused by deregulation of mTORC1 that relieves cytoplasmic retention of Tfe3, leading to direct induction of the Ppargc1b/PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program (PubMed:27913603).|||Expressed throughout embryogenesis (PubMed:19850877). At 5.5 dpc, expression is restricted to extraembryonic tissues; by 6.5 dpc, expressed in both embryonic and extraembryonic tissues (PubMed:19850877). Strong expression is observed in certain tissues including neural ectoderm, headfold and limb buds, while it is weakly expressed in the surrounding endoderm and heart (PubMed:19850877).|||GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of RagA/RRAGA (or RagB/RRAGB), because Arg-164 is located far from the RagC/RRAGC or RagD/RRAGD nucleotide pocket (By similarity). Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity (By similarity).|||Highly expressed in adult heart, pancreas, and prostate with moderate expression in adult brain, kidney, liver, adipose tissue and lung.|||Interacts (via C-terminus) with FNIP1 or FNIP2 (via C-terminus). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator. Interaction with FNIP1 or FNIP2 mediates indirect interaction with the PRKAA1, PRKAB1 and PRKAG1 subunits of 5'-AMP-activated protein kinase (AMPK). Interacts with HSP90AA1 in the presence of FNIP1. Interacts with HSP70, STUB1, CDC37, AHSA1, CCT2, STIP1, PTGES3 and PPP5C (By similarity). Interacts with GABARAP; interaction takes place in the presence of FNIP1 and/or FNIP2 (By similarity). Interacts with RILP; the interaction is direct and promotes association between RILP and RAB34 (By similarity). Interacts with KIF3A and KIF3B (By similarity). Interacts with lactate dehydrogenase LDHA, but not LDHB; the interaction is direct, may preferentially bind LDHA dimers rather than tetramers, and regulates LDHA activity, acting as an uncompetitive inhibitor.|||Lysosome membrane|||Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis (PubMed:23582324, PubMed:27913603, PubMed:32612235). GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:23582324, PubMed:27913603, PubMed:32612235). Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1 (By similarity). The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients (By similarity). Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1 (PubMed:27913603, PubMed:32612235). In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, inactivates mTORC1 and maximizes nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, RagA/RRAGA (or RagB/RRAGB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity). Indirectly acts as a positive regulator of Wnt signaling by promoting mTOR-dependent cytoplasmic retention of MiT/TFE factor TFE3 (PubMed:31272105). Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of TFE3, thereby increasing Wnt signaling (By similarity). Involved in the control of embryonic stem cells differentiation; together with LAMTOR1 it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (PubMed:30595499). Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of TFE3 (PubMed:27913603). In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia: may act by recruiting STK11/LKB1 to primary cilia for activation of AMPK resided at basal bodies, causing mTORC1 down-regulation (By similarity). Together with FNIP1 and/or FNIP2, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (By similarity). Required for starvation-induced perinuclear clustering of lysosomes by promoting association of RILP with its effector RAB34 (By similarity). Regulates glycolysis by binding to lactate dehydrogenase LDHA, acting as an uncompetitive inhibitor (By similarity).|||Nucleus|||Phosphorylation by ULK1 modulates the interaction with GABARAP and is required to regulate autophagy.|||centrosome|||cilium|||cytosol|||spindle http://togogenome.org/gene/10090:Thtpa ^@ http://purl.uniprot.org/uniprot/Q8JZL3 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ThTPase family.|||Binds 1 Mg(2+) ion per subunit.|||Cytoplasm|||Hydrolase highly specific for thiamine triphosphate (ThTP).|||Monomer. http://togogenome.org/gene/10090:Gm21637 ^@ http://purl.uniprot.org/uniprot/E9PWJ8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Iars ^@ http://purl.uniprot.org/uniprot/Q8BU30 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I aminoacyl-tRNA synthetase family.|||Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.|||Cytoplasm|||Part of a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18.|||cytosol http://togogenome.org/gene/10090:Stbd1 ^@ http://purl.uniprot.org/uniprot/Q8C7E7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a cargo receptor for glycogen. Delivers its cargo to an autophagic pathway called glycophagy, resulting in the transport of glycogen to lysosomes.|||Endoplasmic reticulum membrane|||Expressed at high level in glycogen-accumulating organs such as muscle and liver. Trace signals are also found in brain, kidney, and pancreas.|||Interacts with the ATG8 family proteins GABARAP and GABARAPL1 (By similarity). Interacts with several glycogen-associated proteins, such as GYS2 (liver glycogen synthase), GDE (glycogen debranching enzyme), GBE1 (glycogen branching enzyme 1) and EPM2A (Laforin) (By similarity).|||Preautophagosomal structure membrane|||T-tubule|||The C-terminal CBM20 domain is required for the interaction with glycogen.|||The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family protein GABARAPL1.|||Ubiquitinated, which leads to proteasomal degradation. http://togogenome.org/gene/10090:6030458C11Rik ^@ http://purl.uniprot.org/uniprot/Q8BGC1 ^@ Similarity ^@ Belongs to the UPF0489 family. http://togogenome.org/gene/10090:Cyp3a59 ^@ http://purl.uniprot.org/uniprot/D3Z2W7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Npas1 ^@ http://purl.uniprot.org/uniprot/A2RSH6|||http://purl.uniprot.org/uniprot/P97459 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Interacts with ARNT; forms a heterodimer that binds core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) leading to a transcriptional repressor on its target gene TH.|||Expressed in brain in inhibitory interneurons. Also found in spinal cord.|||First detected between embryonic day 15 and day 16.|||May control regulatory pathways relevant to schizophrenia and to psychotic illness. May play a role in late central nervous system development by modulating EPO expression in response to cellular oxygen level. Forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) leading to transcriptional repression on its target gene TH (PubMed:27782878).|||Nucleus http://togogenome.org/gene/10090:Dipk2b ^@ http://purl.uniprot.org/uniprot/Q3TQ46|||http://purl.uniprot.org/uniprot/Q8C3I9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the DIPK family.|||Secreted http://togogenome.org/gene/10090:2300002M23Rik ^@ http://purl.uniprot.org/uniprot/Q8BM15 ^@ Developmental Stage|||Subcellular Location Annotation|||Subunit ^@ At 16.5 dpc, present in rib cartilage (at protein level).|||Binds to numerous extracellular matrix proteins.|||extracellular matrix http://togogenome.org/gene/10090:Lgals12 ^@ http://purl.uniprot.org/uniprot/Q91VD1 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Binds lactose. May participate in the apoptosis of adipocytes.|||Contains two homologous but distinct carbohydrate-binding domains.|||Nucleus http://togogenome.org/gene/10090:Kpna7 ^@ http://purl.uniprot.org/uniprot/C0LLJ0 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the importin alpha family.|||Binds to importin subunit beta-1/KPNB1 via the IBB domain; this complex dissociates in the presence of RAN-GTP. Shows a limited binding to the RB1 nuclear localization signal (NLS), but not to the SV40, nor NPM1 NLSs. Interacts with RSL1D1.|||Expressed at high levels in germinal vesicle-stage oocytes, as well as in zygotes and 2-cell embryos (at protein level). Drastically down-regulated after the 2-cell stage.|||Expressed predominantly in ovary. Isoform 1 is the predominant form.|||Functions in nuclear protein import.|||Mutant mice exhibit abnormal preimplantation development. About half of the mutant embryos fail to develop into the blastocyst stage, or are delayed. Lethality is greater among female than among male embryos.|||Nucleus http://togogenome.org/gene/10090:Hsf3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J251|||http://purl.uniprot.org/uniprot/D0VYS2|||http://purl.uniprot.org/uniprot/E9QNK9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the HSF family.|||Cytoplasm|||DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription of non-classical heat-shock genes such as PDZD2 and PROM2. Protects cells against heat shock and proteotoxic stress.|||Nucleus http://togogenome.org/gene/10090:Eif3a ^@ http://purl.uniprot.org/uniprot/P23116 ^@ Function|||PTM|||RNA Editing|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit A family.|||Cytoplasm|||Interacts with KRT7 (By similarity). Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3L and EIF3K. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with EIF4G1 and PIWIL2.|||Nucleus|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation.|||RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Some positions are modified by RNA editing via nucleotide deletion, up to position 787. The unedited version gives rise to centrosomin-B (shown here). The fully edited version gives rise to centrosomin-A, in which the C-terminal sequence is replaced up to position 787 by Ser-Ile-Val-Ala-STOP. A combination of alternative splicing and RNA editing resulting in this template G deletion could also explain the generation of centrosomin-A mRNA.|||centrosome http://togogenome.org/gene/10090:Ide ^@ http://purl.uniprot.org/uniprot/Q8CGB9 ^@ Similarity ^@ Belongs to the peptidase M16 family. http://togogenome.org/gene/10090:Aurkb ^@ http://purl.uniprot.org/uniprot/O70126 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Lys-220 by KAT5 at kinetochores, increasing AURKB activity and promoting accurate chromosome segregation in mitosis.|||Activity is greatly increased when AURKB is within the CPC complex. In particular, AURKB-phosphorylated INCENP acts as an activator of AURKB. Positive feedback between HASPIN and AURKB contributes to CPC localization.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.|||Chromosome|||Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; predominantly independent AURKB- and AURKC-containing complexes exist. Associates with RACGAP1 during M phase. Interacts with CDCA1, EVI5, JTB, NDC80, PSMA3, SEPTIN1, SIRT2 and TACC1. Interacts with SPDYC; this interaction may be required for proper localization of active, Thr-237-phosphorylated AURKB form during prometaphase and metaphase. Interacts with p53/TP53. Interacts (via the middle kinase domain) with NOC2L (via the N- and C-terminus domains). Interacts with TTC28 (By similarity). Interacts with RNF2/RING1B (PubMed:24034696).|||Expressed in testis, intestine and spleen. All of them are tissues that contain a large number of proliferating cells. Expressed during S phase, in a cell-cycle-dependent fashion.|||Midbody|||Nucleus|||Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (By similarity). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (By similarity). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (By similarity). Required for central/midzone spindle assembly and cleavage furrow formation (By similarity). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (By similarity). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (By similarity). Phosphorylation of INCENP leads to increased AURKB activity (By similarity). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (By similarity). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (By similarity). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863). AURKB is also required for kinetochore localization of BUB1 and SGO1 (By similarity). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (By similarity). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (PubMed:24034696). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (By similarity). Phosphorylates KRT5 during anaphase and telophase (PubMed:29518391).|||Strongly expressed in 8.5 and 12.5 dpc.|||The phosphorylation of Thr-237 requires the binding to INCENP and occurs by means of an autophosphorylation mechanism. Thr-237 phosphorylation is indispensable for the AURKB kinase activity.|||Ubiquitinated by different BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complexes. Ubiquitinated by the BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex, ubiquitination leads to removal from mitotic chromosomes and is required for cytokinesis. During anaphase, the BCR(KLHL21) E3 ubiquitin ligase complex recruits the CPC complex from chromosomes to the spindle midzone and mediates the ubiquitination of AURKB. Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. Deubiquitinated by USP35; inhibiting CDH1-mediated degradation of AURKB.|||centromere|||kinetochore|||spindle http://togogenome.org/gene/10090:Dync2h1 ^@ http://purl.uniprot.org/uniprot/Q45VK7 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein heavy chain family.|||Cell membrane|||Cytoplasm|||Detected in brain, lung, spleen and kidney (at protein level). Enriched in the ependymal layer lining the lateral ventricles (at protein level).|||Expressed at 9.5 and 10.5 dpc in the neural tube where it is enriched in rostral part.|||May function as a motor for intraflagellar retrograde transport. Functions in cilia biogenesis. According to PubMed:8666668, it may play a role in transport between endoplasmic reticulum and Golgi or organization of the Golgi in cells.|||Mice homozygous for Dync2h1 null alleles die at approximately 12.5 dpc with abnormal brain morphology, frequent heart-looping and occasionally with polysyndactily. Cilia have abnormal morphology.|||The cytoplasmic dynein complex 2 is probably composed by a heavy chain DYNC2H1 homodimer and a number of DYNC2LI1 light intermediate chains.|||cilium axoneme http://togogenome.org/gene/10090:Pik3r6 ^@ http://purl.uniprot.org/uniprot/Q3U6Q4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Heterodimer of a catalytic subunit (PIK3CG) and a regulatory (PIK3R6) subunit. The binding of PIK3R6 to PIK3CG may exclude the binding of PIK3R5 to PIK3CG (PubMed:16476736, PubMed:15797027). Interacts with beta-gamma G protein dimers (PubMed:16476736). Interacts with PDE3B and RAPGEF3; form a signaling complex that regulates phosphatidylinositol 3-kinase gamma in angiogenesis (By similarity).|||Highly expressed in heart. In a lower extent, also expressed in brain, spleen, lung, liver, kidney, prostate, thyroid, salivary gland, dendritic cells, macrophages and neutrophils.|||Regulatory subunit of the PI3K gamma complex. Acts as an adapter to drive activation of PIK3CG by beta-gamma G protein dimers. The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G proteins than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. Recruits of the PI3K gamma complex to a PDE3B:RAPGEF3 signaling complex involved in angiogenesis; signaling seems to involve RRAS. http://togogenome.org/gene/10090:Cfap97d1 ^@ http://purl.uniprot.org/uniprot/Q9DAN9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the CFAP97 family.|||Expressed exclusively in testis.|||Expression starts at postnatal day 20 and continues throughout adulthood.|||Male subfertility. Sperm show an impaired ability to penetrate the zona pellucida and abnormal motility characterized by frequent stalling in the anti-hook position with the flagellum and hook of the sperm head pointing in opposite directions. Sperm flagella lack outer microtubule doublet 4 in 63% of mutants while doublet 7 is missing in 14.8% of mutants. A small number of mutants have multiple doublets missing but these are relatively rare: the 4th and 7th doublets are missing in 1.6% of mutants; the 4th, 5th and 7th doublets are missing in 3.7%; the 4th, 5th and 6th doublets are missing in 1.23%; and the 4th, 5th, 6th and 7th doublets are missing in 1.23%.|||Required for male fertility through its role in axonemal doublet stabilization which is essential for sperm motility and fertilization. http://togogenome.org/gene/10090:P2rx7 ^@ http://purl.uniprot.org/uniprot/C8YIX4|||http://purl.uniprot.org/uniprot/F8WI93|||http://purl.uniprot.org/uniprot/Q3UN00|||http://purl.uniprot.org/uniprot/Q8CHP4|||http://purl.uniprot.org/uniprot/Q9Z1M0 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylation at Arg-125 is necessary and sufficient to activate P2RX7 and gate the channel.|||Belongs to the P2X receptor family.|||Cell membrane|||Functional P2XRs are organized as homomeric and heteromeric trimers. Interacts with LAMA3, ITGB2, ACTB, ACTN4, SVIL, MPP3, HSPA1, HSPCB, HSPA8, PIK230 and PTPRB (By similarity). Interacts (via C-terminus) with EMP2 (By similarity).|||Membrane|||Palmitoylation of several cysteines in the C-terminal cytoplasmic tail is required for efficient localization to cell surface.|||Phosphorylation results in its inactivation.|||Receptor for ATP that acts as a ligand-gated ion channel.|||Receptor for ATP that acts as a ligand-gated ion channel. Responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells. In the absence of its natural ligand, ATP, functions as a scavenger receptor in the recognition and engulfment of apoptotic cells. http://togogenome.org/gene/10090:Eml5 ^@ http://purl.uniprot.org/uniprot/Q8BQM8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the WD repeat EMAP family.|||May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.|||cytoskeleton http://togogenome.org/gene/10090:Skida1 ^@ http://purl.uniprot.org/uniprot/Q80YR3 ^@ Similarity ^@ Belongs to the DACH/dachshund family. http://togogenome.org/gene/10090:Foxn1 ^@ http://purl.uniprot.org/uniprot/Q32MU3|||http://purl.uniprot.org/uniprot/Q5SYK1|||http://purl.uniprot.org/uniprot/Q61575 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Bone marrow (at protein level). Expressed in thymus and skin.|||Defects in FOXN1 are the cause of the nude/severe combined immunodeficiency (SCID) phenotype which is characterized by athymia and hairlessness. Mice develop largely normal hair follicles and produce hair shafts. However, presumably because of a lack of certain hair keratins, the hair shafts that are generated twist and coil in the hair follicle infundibulum, which becomes dilated. Since hair shafts fail to penetrate the epidermis, macroscopic nudity results and generates the grossly misleading impression that nude mice are hairless.|||Mice exhibit nude skin phenotype and acute thymic atrophy with a severe early block in thymic epithelial cells (TECs) differentiation. A more severe deterioration seen in medullary thymic epithelial cells (mTECs) than in cortical thymic epithelial cells (cTECs).|||Nucleus|||Transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs) both in the prenatal and postnatal thymus. Acts as a master regulator of the TECs lineage development and is required from the onset of differentiation in progenitor TECs in the developing fetus to the final differentiation steps through which TECs mature to acquire their full functionality. Regulates, either directly or indirectly the expression of a variety of genes that mediate diverse aspects of thymus development and function, including MHC Class II, DLL4, CCL25, CTSL, CD40 and PAX1. Regulates the differentiation of the immature TECs into functional cortical TECs (cTECs) and medullary TECs (mTECs) (PubMed:22072979). Essential for maintenance of mTECs population in the postnatal thymus (PubMed:19955175). Involved in the morphogenesis and maintenance of the three-dimensional thymic microstructure which is necessary for a fully functional thymus (PubMed:21109991). Plays an important role in the maintenance of hematopoiesis and particularly T lineage progenitors within the bone marrow niche with age (PubMed:24184560). Essential for the vascularization of the thymus anlage (PubMed:19853842). Promotes the terminal differentiation of epithelial cells in the epidermis and hair follicles, partly by negatively regulating the activity of protein kinase C (PubMed:17459087). http://togogenome.org/gene/10090:Syt3 ^@ http://purl.uniprot.org/uniprot/O35681 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the synaptotagmin family.|||Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.|||Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain. Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis. Plays a role in dendrite formation by melanocytes.|||Cell membrane|||Homodimer; disulfide-linked via the cysteine motif (PubMed:10531343). Can also form heterodimers with SYT6, SYT9 and SYT10 (PubMed:10531343, PubMed:10531344).|||The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds.|||The first C2 domain mediates Ca(2+)-dependent phospholipid binding.|||secretory vesicle membrane http://togogenome.org/gene/10090:Prl7a2 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0L8|||http://purl.uniprot.org/uniprot/O54831 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expression restricted to the placental tissue. Expressed only in the spongiotrophoblasts.|||Not detected until later in gestation.|||Secreted http://togogenome.org/gene/10090:Mdm1 ^@ http://purl.uniprot.org/uniprot/B2RPU6|||http://purl.uniprot.org/uniprot/B7SNM8|||http://purl.uniprot.org/uniprot/E9PW14|||http://purl.uniprot.org/uniprot/E9Q0B1|||http://purl.uniprot.org/uniprot/Q9D067 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MDM1 family.|||Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules.|||Nucleus|||Widely expressed. Expressed at high levels in the testis.|||centriole|||centrosome http://togogenome.org/gene/10090:Cd74 ^@ http://purl.uniprot.org/uniprot/P04441|||http://purl.uniprot.org/uniprot/Q3U4Q8 ^@ Caution|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome.|||Cell membrane|||Endoplasmic reticulum membrane|||Endosome|||Expressed in thymus and lymph noodes (PubMed:8977190). Expressed by antigen-presenting cells (APCs) (PubMed:11483509, PubMed:12417635).|||Expressed in thymus and lymph noodes.|||Expression is induced by IFNG and LPS, through CIITA.|||Interacts with the mature form of CTSL; the complex survive in neutral pH environment.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Late endosome|||Lysosome|||Mutants for Long isoform or Short isoform exhibit similar functional capabilities.|||Nonamer composed of three alpha/beta/gamma heterotrimers. Interacts with CD44; this complex is essential for the MIF-induced signaling cascade that results in B cell survival.|||Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to compartments where peptide loading of class II takes place. Enhance also the stimulation of T-cell responses through interaction with CD44.|||Secreted|||Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs).|||trans-Golgi network http://togogenome.org/gene/10090:Wrap73 ^@ http://purl.uniprot.org/uniprot/Q9JM98 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with SSX2IP (PubMed:26675238).|||The SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome. Required for the centrosomal localization of SSX2IP and normal mitotic bipolar spindle morphology. Required for the targeting of centriole satellite proteins to centrosomes such as of PCM1, SSX2IP, CEP290 and PIBF1/CEP90. Required for ciliogenesis and involved in the removal of the CEP97:CCP110 complex from the mother centriole. Involved in ciliary vesicle formation at the mother centriole and required for the docking of vesicles to the basal body during ciliogenesis; may promote docking of RAB8A- and ARL13B-containing vesicles (By similarity).|||Ubiquitous.|||centrosome http://togogenome.org/gene/10090:En1 ^@ http://purl.uniprot.org/uniprot/P09065 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the engrailed homeobox family.|||Nucleus|||Required for proper formation of the apical ectodermal ridge and correct dorsal-ventral patterning in the limb. http://togogenome.org/gene/10090:Col4a4 ^@ http://purl.uniprot.org/uniprot/Q9QZR9 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.|||Belongs to the type IV collagen family.|||Expressed in Bruch's membrane, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, inner limiting membrane and around the blood vessels of the retina (at protein level) (PubMed:29777959). Highly expressed in kidney and lung (PubMed:7962065). Detected at lower levels in heart, muscle and skin (PubMed:7962065).|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The expression of collagen IV undergoes a developmental shift in the developing lens capsule. During the early stages of lens capsule development expression of collagens alpha 1(IV), alpha 2(IV), alpha 5(IV) and alpha 6(IV) is observed; this is consistent with the presence of fibrillar alpha 1(IV)-alpha 1(IV)-alpha 2(IV) protomers and of elastic alpha 5(IV)-alpha 5(IV)-alpha 6(IV) protomers. In the later stages of development components of the more cross-linked alpha 3(IV)-alpha 4(IV)-alpha 5(IV) protomer appear.|||The kidneys of transgenic mice where the 5' portions of both COL4A3 and COL4A4 and the shared intergenic promoter region were deleted exhibit morphological and ultrastructural features characteristic of the human hereditary disorder Alport syndrome, including disorganization and multilamellar structure of the GBM and delayed onset glomerulonephritis.|||The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.|||There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite protomer, respectively (By similarity). Associates with LAMB2 at the neuromuscular junction and in GBM.|||Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.|||Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.|||basement membrane http://togogenome.org/gene/10090:Tmem45b ^@ http://purl.uniprot.org/uniprot/Q8VCZ2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM45 family.|||Endosome membrane|||Lysosome membrane|||Plays a role in innate immunity.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Hoxd11 ^@ http://purl.uniprot.org/uniprot/A2ASM7|||http://purl.uniprot.org/uniprot/P23813 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Expressed during development of the posterior part of the body.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Spag9 ^@ http://purl.uniprot.org/uniprot/B8X349|||http://purl.uniprot.org/uniprot/Q58A65 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JIP scaffold family.|||Cytoplasm|||Highly expressed in brain, kidney, liver, heart.|||Homodimer (By similarity). The homodimer interacts with ARF6, forming a heterotetramer (By similarity). Homooligomer (By similarity). Interacts with MAX, MAPK8, MAPK14, MAP3K3, MYC, and MAP2K4 (PubMed:12391307). Interacts with KNS2 (PubMed:15987681). Interaction with KNS2 is important in the formation of ternary complex with MAPK8 (PubMed:15767678). Interacts with PIP4P1 (By similarity). Interacts with PIKFYVE (PubMed:19056739).|||Lysosome membrane|||Phosphorylated by MAPK8 and MAPK14.|||The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:12391307, PubMed:15767678). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (By similarity). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (PubMed:19056739).|||Up-regulated during neuronal differentiation.|||perinuclear region http://togogenome.org/gene/10090:Or8b44 ^@ http://purl.uniprot.org/uniprot/Q7TRC7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rnf151 ^@ http://purl.uniprot.org/uniprot/Q9CQ29 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in testis. Expressed in round spermatids of the stages VII-VIII semniniferous tubules. Expressed in elongating spermatids of stages VIII-IX seminiferous tubules (at protein level).|||Interacts with DTNBP1.|||May be involved in acrosome formation of spermatids.|||Nucleus http://togogenome.org/gene/10090:Eif4enif1 ^@ http://purl.uniprot.org/uniprot/Q8BY82|||http://purl.uniprot.org/uniprot/Q9EST3 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 4E-T/EIF4E-T family.|||Cytoplasm|||EIF4E-binding protein that regulates translation and stability of mRNAs in processing bodies (P-bodies) (PubMed:25456498). Plays a key role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (By similarity). Acts as a binding platform for multiple RNA-binding proteins: promotes deadenylation of mRNAs via its interaction with the CCR4-NOT complex, and blocks decapping via interaction with eIF4E (EIF4E and EIF4E2), thereby protecting deadenylated and repressed mRNAs from degradation (By similarity). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (PubMed:25456498). Promotes miRNA-mediated translational repression (By similarity). Involved in mRNA translational repression mediated by the miRNA effector TNRC6B by protecting TNRC6B-targeted mRNAs from decapping and subsequent decay (By similarity). Required for the formation of P-bodies (By similarity). Also acts as a nucleoplasmic shuttling protein, which mediates the nuclear import of EIF4E and DDX6 by a piggy-back mechanism (By similarity).|||Highly expressed in developing oocytes.|||Interacts (via YXXXXLphi motif) with EIF4E (PubMed:16343815). Interacts (via YXXXXLphi motif) with EIF4E2 (By similarity). Interacts with DDX6. Interacts with CSDE1/UNR (By similarity). Interacts with CNOT1; promoting association with the CCR4-NOT complex (By similarity). Interacts with LSM14A; promoting EIF4ENIF1 localization to P-bodies (By similarity). Interacts with PATL1 (By similarity). Interacts with importin beta only in the presence of importin alpha, suggesting a direct interaction with importin alpha (By similarity). Interacts with APOBEC3G in an RNA-dependent manner (By similarity).|||Intrinsically disordered protein with multiple low-complexity regions that confer binding to multiple RNA translation, deadenylation and decapping factors.|||Nucleus|||Nucleus speckle|||PML body|||Phosphorylation by MAPK8/JNK1 and or MAPK9/JNK2 in response to oxidative stress promotes P-body assembly (By similarity). Phosphorylated during meiotic maturation (PubMed:16343815).|||The YXXXXLphi motif mediates interaction with eIF4E (EIF4E and EIF4E2). http://togogenome.org/gene/10090:Tceal5 ^@ http://purl.uniprot.org/uniprot/Q8CCT4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TFS-II family. TFA subfamily.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Or51a43 ^@ http://purl.uniprot.org/uniprot/Q8VH21 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prelid3b ^@ http://purl.uniprot.org/uniprot/Q9CYY7 ^@ Similarity ^@ Belongs to the slowmo family. http://togogenome.org/gene/10090:Clcn7 ^@ http://purl.uniprot.org/uniprot/E9PYL4|||http://purl.uniprot.org/uniprot/O70496|||http://purl.uniprot.org/uniprot/Q6RUT9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates undegraded endocyted material in neurons or renal proximal tubular cells. Almost all ClC-7-deficient neurons die.|||Belongs to the chloride channel (TC 2.A.49) family.|||Belongs to the chloride channel (TC 2.A.49) family. ClC-7/CLCN7 subfamily.|||Chloride channel 7 are heteromers of alpha (CLCN7) and beta (OSTM1) subunits.|||Liver, spleen, kidneys and brain.|||Lysosome membrane|||Membrane|||Slowly voltage-gated channel mediating the exchange of chloride ions against protons (PubMed:16525474, PubMed:19661288). Functions as antiporter and contributes to the acidification of the lysosome lumen and may be involved in maintaining lysosomal pH (PubMed:16525474, PubMed:19661288). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (By similarity). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity). http://togogenome.org/gene/10090:Rbfox1 ^@ http://purl.uniprot.org/uniprot/Q9JJ43 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the C-terminus of ATXN2.|||Cytoplasm|||Detected in brain (at protein level). Detected in heart, brain, neurons, skeletal muscle and embryo.|||Nucleus|||RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Prevents binding of U2AF2 to the 3'-splice site. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis. http://togogenome.org/gene/10090:Zc4h2 ^@ http://purl.uniprot.org/uniprot/Q68FG0 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cytoplasm|||Expressed in embryonic and adult brain and spinal cord.|||In all brain areas, expression levels are high during embryonic development and decrease postanatally.|||Nucleus|||Plays a role in interneurons differentiation. Involved in neuronal development and in neuromuscular junction formation.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Rnd1 ^@ http://purl.uniprot.org/uniprot/Q8BLR7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Binds GRB7 and PLXNB1. Interacts with PLXNA2. Interacts with UBXD5 (By similarity).|||Cell membrane|||Lacks intrinsic GTPase activity. Has a low affinity for GDP, and constitutively binds GTP. Controls rearrangements of the actin cytoskeleton. Induces the Rac-dependent neuritic process formation in part by disruption of the cortical actin filaments. Causes the formation of many neuritic processes from the cell body with disruption of the cortical actin filaments (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Ppih ^@ http://purl.uniprot.org/uniprot/Q3UWH9|||http://purl.uniprot.org/uniprot/Q4G0C5|||http://purl.uniprot.org/uniprot/Q9D868 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cyclophilin-type PPIase family.|||Belongs to the cyclophilin-type PPIase family. PPIase H subfamily.|||Cytoplasm|||Inhibited by cyclosporin A.|||Interacts directly with PRPF4. Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Heterodimer with PRPF18. Heterodimer with PRPF18 (By similarity).|||Nucleus speckle|||PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Participates in pre-mRNA splicing. May play a role in the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome. May act as a chaperone.|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. http://togogenome.org/gene/10090:U2af1 ^@ http://purl.uniprot.org/uniprot/Q9D883 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the splicing factor SR family.|||Expressed in primary spermatocytes and elongating spermatids (at protein level).|||Identified in the spliceosome C complex (By similarity). Heterodimer with U2AF2 (By similarity). Interacts (via RS domain) with PHF5A (via N-terminus) (PubMed:18758164). Interacts with ZRANB2 (By similarity). Interacts with SDE2 (By similarity). Interacts with SF3B1 (By similarity).|||Nucleus|||Nucleus speckle|||Plays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3'-splice site selection. Recruits U2 snRNP to the branch point. Directly mediates interactions between U2AF2 and proteins bound to the enhancers and thus may function as a bridge between U2AF2 and the enhancer complex to recruit it to the adjacent intron (By similarity).|||The C-terminal SR-rich domain is required for interactions with SR proteins and the splicing regulators TRA and TRA2, and the N-terminal domain is required for formation of the U2AF1/U2AF2 heterodimer. http://togogenome.org/gene/10090:Serpinb2 ^@ http://purl.uniprot.org/uniprot/P12388|||http://purl.uniprot.org/uniprot/Q542A3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the serpin family.|||Belongs to the serpin family. Ov-serpin subfamily.|||Cytoplasm|||Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1. Not required for normal murine development or survival.|||Interacts with PSMB1.|||The signal sequence is not cleaved.|||extracellular space http://togogenome.org/gene/10090:Pom121l2 ^@ http://purl.uniprot.org/uniprot/Q5SW25 ^@ Similarity ^@ Belongs to the POM121 family. http://togogenome.org/gene/10090:Tas2r129 ^@ http://purl.uniprot.org/uniprot/Q7M709 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Vinac1 ^@ http://purl.uniprot.org/uniprot/A2AP89 ^@ Similarity ^@ Belongs to the vinculin/alpha-catenin family. http://togogenome.org/gene/10090:Agl ^@ http://purl.uniprot.org/uniprot/F8VPN4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycogen debranching enzyme family.|||Cytoplasm|||Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation. http://togogenome.org/gene/10090:Slc26a4 ^@ http://purl.uniprot.org/uniprot/Q9R155 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Cell membrane|||Highly expressed in the kidney (at protein level) (PubMed:11274445, PubMed:35601831). Throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea (PubMed:10449762). Expressed in the parotid gland (PubMed:18565999).|||Interacts with IQGAP1 (PubMed:35601831). This interaction enhances the chloride-bicarbonate exchange activity of SLC26A4 (By similarity).|||Sodium-independent transporter of chloride and iodide (By similarity). Mediates electroneutral iodide-chloride, iodide-bicarbonate and chloride-bicarbonate exchange with 1:1 stoichiometry (PubMed:11274445, PubMed:18565999). Mediates elctroneutral chloride-formate exchange (By similarity). http://togogenome.org/gene/10090:Scrt1 ^@ http://purl.uniprot.org/uniprot/Q99M85 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snail C2H2-type zinc-finger protein family.|||Detected throughout the spinal cord except in the ventricular zone surrounding the central canal, which contains proliferating neurons, and dorsal root ganglia at 11.5 dpc. At 12.5 dpc, detected in the telencephalon, and by 14.5 dpc a distinct laminar pattern of expression was seen in regions adjacent to the ventricular zone. In the developing eye, expression was detected in the inner nuclear layer of the retina beginning at 13.5 dpc.|||Interacts (via SNAG domain) with LIMD1 (via LIM domains), WTIP (via LIM domains) and AJUBA (via LIM domains).|||Nucleus|||The N-terminal non zinc-finger region mediates the repressor activity.|||Transcriptional repressor that binds E-box motif CAGGTG (By similarity). Appears to function downstream of proneural bHLH proteins in promoting neural differentiation. http://togogenome.org/gene/10090:Npffr2 ^@ http://purl.uniprot.org/uniprot/Q924H0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity). http://togogenome.org/gene/10090:Mxd3 ^@ http://purl.uniprot.org/uniprot/Q80US8 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with SIN3A AND SIN3B. Interacts with RNF17.|||Expressed during neural and epidermal differentiation. Expression restricted to proliferating cells prior to differentiation. Specifically expressed in the S phase of the cell cycle in neuronal progenitor cells. In the developing embryo, detected from 9.5 to 12.5 dpc especially in the ventricular zone of the neuroepithelia, in the progression zone of the limb buds and in the aortic arches and liver. In the spinal cord at embryonic days 10.5, 11.5 and 12.5 dpc, expressed in the cells at the perimeter of the ventricular zone. In the developing epidermis, expressed only in the uppermost differentiated cell layers underneath the stratum corneum.|||Expressed only in the proliferating areas of the testis and thymus.|||Mice deficient for Mxd3 show increased sensitivity of neuronal and lymphoid cells to gamma-radiation induced apoptosis.|||Nucleus|||Transcriptional repressor. Binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. Antagonizes MYC transcriptional activity by competing for MAX and suppresses MYC dependent cell transformation. http://togogenome.org/gene/10090:Mrgprb5 ^@ http://purl.uniprot.org/uniprot/Q91ZB9|||http://purl.uniprot.org/uniprot/W8W3Q3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Membrane|||Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Zfyve26 ^@ http://purl.uniprot.org/uniprot/Q5DU37 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ZFYVE26 family.|||Interacts with AP5Z1, AP5B1, AP5S1 and SPG11. Interacts with TTC19 and KIF13A (By similarity).|||Midbody|||Phosphatidylinositol 3-phosphate-binding protein required for the abcission step in cytokinesis: recruited to the midbody during cytokinesis and acts as a regulator of abcission. May also be required for efficient homologous recombination DNA double-strand break repair (By similarity).|||The FYVE-type zinc finger mediates binding to phosphatidylinositol 3-phosphate and recruitment to the midbody during cytokinesis.|||centrosome http://togogenome.org/gene/10090:Ghsr ^@ http://purl.uniprot.org/uniprot/Q0VBE5|||http://purl.uniprot.org/uniprot/Q99P50 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine) (By similarity). http://togogenome.org/gene/10090:Dclk1 ^@ http://purl.uniprot.org/uniprot/A3KN70|||http://purl.uniprot.org/uniprot/H7BX36|||http://purl.uniprot.org/uniprot/Q8CCN4|||http://purl.uniprot.org/uniprot/Q9JLM6|||http://purl.uniprot.org/uniprot/Q9JLM8 ^@ Function|||Similarity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system (By similarity). http://togogenome.org/gene/10090:Rac3 ^@ http://purl.uniprot.org/uniprot/P60764 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rho family.|||Cell membrane|||Cytoplasm|||Endomembrane system|||Interacts with the GEF protein DOCK7, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with C1D. Interacts (via C-terminal region) with CIB1; the interaction induces their association with the cytoskeleton upon alpha-IIb/beta3 integrin-mediated adhesion. Interacts with NRBP.|||Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles. Promotes cell adhesion and spreading on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner.|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Regulated by the GEF protein DOCK7.|||Ubiquitinated at Lys-166 in a FBXL19-mediated manner; leading to proteasomal degradation.|||cytoskeleton|||lamellipodium|||perinuclear region http://togogenome.org/gene/10090:Or8c9 ^@ http://purl.uniprot.org/uniprot/Q7TRD6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bsph2 ^@ http://purl.uniprot.org/uniprot/Q0Q236 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the seminal plasma protein family.|||Binds sperm in vitro but has no effect on sperm capacitation. Also binds gelatin and heparin, but not chondroitin sulfate B or phospholipid liposomes.|||Epididymis.|||Secreted http://togogenome.org/gene/10090:Tmco5 ^@ http://purl.uniprot.org/uniprot/Q9D9D5 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMCO5 family.|||Detected in testis at 28 days after birth and expression is maintained (PubMed:28742876). Expressed by testicular cells and testicular sperm but not mature sperm (PubMed:28742876).|||Membrane|||Only detected in testis (at protein level). http://togogenome.org/gene/10090:Pla2g4c ^@ http://purl.uniprot.org/uniprot/Q64GA5 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Calcium-independent phospholipase, lysophospholipase and O-acyltransferase involved in phospholipid remodeling. Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with choline and ethanolamine head groups, producing lysophospholipids that are used in deacylation-reacylation cycles. Transfers the sn-1 fatty acyl from one lysophospholipid molecule to the sn-2 position of another lysophospholipid to form diacyl, alkylacyl and alkenylacyl glycerophospholipids. Cleaves ester bonds but not alkyl or alkenyl ether bonds at the sn-1 position of lysophospholipids. Catalyzes sn-2 fatty acyl transfer from phospholipids to the sn-2 position of 1-O-alkyl or 1-O-alkenyl lysophospholipids with lower efficiency.|||Highly expressed in ovary, where it localizes to oocytes in preantral and antral stage follicles (at protein level). Not detected in other tissues tested.|||Nucleus envelope|||Strongly expressed in oocytes at the germinal vesicle stage, and in zygotes (at protein level). Maternal expression persists in embryos at the 2-cell stage but then declines rapidly and is completely lost by the morula stage (at protein level).|||cell cortex|||nucleoplasm|||spindle http://togogenome.org/gene/10090:Lemd2 ^@ http://purl.uniprot.org/uniprot/Q6DVA0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Embryonic lethal by 11.5 dpc (PubMed:25790465). At 10.5 dpc most tissues are substantially reduced in size, specifically neural and heart structures are developmentally less advanced and/or abnormal (PubMed:25790465). At 10.5 dpc hyperactive MAPK and AKT signaling has been observed (PubMed:25790465). Heart-specific knockout mice exhibit a reduction in body size and die shortly after birth due to heart abnormalities (PubMed:36377660). During transthoracic echocardiography, reduction in both ejection fraction (EF) and fractional shortening (FS) (PubMed:36377660). Systolic dysfunction with severely impaired contraction of the left ventricle (PubMed:36377660). Increase in nuclear envelope deformations, DNA damage, and cellular apoptosis in the heart under mechanical stress (PubMed:36377660).|||Expressed at detectable levels throughout later stages of mouse development such as 12 dpc, 14 dpc, 16 dpc and 18 dpc.|||Interacts (via N-terminus) with LMNA isoform C (via C-terminus) (in vitro) (PubMed:16339967). Interacts (via LEM domain) with BANF1 (By similarity). Interacts (via C-terminus) with CHMP7 (By similarity). Interacts (via N-terminus) with tubulin; the interaction causes microtubule bundling and stabilization (in vitro) (By similarity).|||Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization and maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis (PubMed:16339967). Plays a role as transmembrane adapter for the endosomal sorting complexes required for transport (ESCRT), and is thereby involved in ESCRT-mediated NE reformation (By similarity). Promotes ESCRT-mediated NE closure by recruiting CHMP7 and downstream ESCRT-III proteins IST1/CHMP8 and CHMP2A to the reforming NE during anaphase (By similarity). During nuclear reassembly, condenses into a liquid-like coating around microtubule spindles and coassembles with CHMP7 to form a macromolecular O-ring seal at the confluence between membranes, chromatin, and the spindle to facilitate early nuclear sealing (By similarity). Plays a role in the organization of heterochromatin associated with the NE and in the maintenance of NE organization under mechanical stress (PubMed:36377660). Required for embryonic development and is involved in regulation of several signaling pathways such as MAPK and AKT (PubMed:25790465). Required for myoblast differentiation involving regulation of ERK signaling (PubMed:17062158, PubMed:19720741). Essential for cardiac homeostasis and proper heart function (PubMed:36377660).|||Nucleus envelope|||Nucleus inner membrane|||Phosphorylated; strongly phosphorylated in mitosis compared to G1/S.|||The LEM domain is required for inner nuclear membrane (INM) localization and contains a BANF1 conserved binding motif which allows localization to chromatin (By similarity). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disk, both the LEM domain and the disordered regions are necessary for localization to the NE core (By similarity).|||The disordered regions, also named low complexity domain, confer the ability to phase separate (By similarity). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disks, both the LEM domain and the disordered regions are necessary for localization to the NE core (By similarity). During NE reformation, the proline-arginine-rich sequence within the disordered region binds microtubules, targeting LEM2 condensation to spindle microtubules traversing the nascent NE (By similarity).|||The winged-helix (WH) region (residues 403-511) activates the ESCRT-II/ESCRT-III hybrid protein, CHMP7, to form co-oligomeric rings around spindle microtubules to facilitate early nuclear sealing.|||Ubiquitously expressed, including liver, brain, heart, skeletal muscle, lung, testis, spleen, kidney and white adipose tissue.|||spindle http://togogenome.org/gene/10090:Srpx2 ^@ http://purl.uniprot.org/uniprot/Q8R054 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a ligand for the urokinase plasminogen activator surface receptor. Plays a role in angiogenesis by inducing endothelial cell migration and the formation of vascular network (cords). Involved in cellular migration and adhesion. Increases the phosphorylation levels of FAK. Interacts with and increases the mitogenic activity of HGF. Promotes synapse formation. Required for ultrasonic vocalizations.|||Cell surface|||Contains chondroitin sulfate chains.|||Cytoplasm|||Expressed in angiogenic endothelial cells (at protein level).|||Forms homooligomers. Interacts with PLAUR (via the UPAR/Ly6 domains), ADAMTS4 and CTSB. Interacts with HGF; the interaction increases the mitogenic activity of HGF (By similarity).|||Secreted|||Synapse http://togogenome.org/gene/10090:Bcar3 ^@ http://purl.uniprot.org/uniprot/Q9QZK2 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the lung and brain, with lower expression in splenic lymphocytes and liver (at protein level) (PubMed:19365570). Expressed in splenic lymphocytes (at protein level) (PubMed:19365570). Expressed in the lymph node cortical region, periphery of the splenic white pulp and in alveolar lung fibroblasts (PubMed:19365570). Expressed in epithelial cells in the lens equatorial region and early stage nucleated cortical lens fiber cells (PubMed:19365570). Expressed in the thymus (PubMed:10438950). Expressed in B-cells (PubMed:12517963).|||Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:12517963). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (By similarity). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:10896938). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (PubMed:25499443). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (PubMed:25499443). Regulates EGF-induced DNA synthesis (By similarity). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (PubMed:19365570). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (PubMed:22801373). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (PubMed:22801373). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (PubMed:10896938). However, in a contrasting study, lacks GEF activity towards RAP1 (By similarity).|||Cytoplasm|||Knockout mice are generally normal and viable (PubMed:19365570). Retinal white circular lesions in anterior chamber derived from the lens cortex (PubMed:19365570). Retinal lens is partially opaque and irregular in structure, with rupture leading to cortical lens fragments floating in the aqueous humor (PubMed:19365570). Abnormally deep anterior chamber with anterior synechiae, ectropion uveae, mild to moderate retinal ganglion loss, and a small pigmented pre-retinal membrane overlying the optic nerve (PubMed:19365570). Reduced phosphorylation of AKT1 and BCAR1 in lens epithelial cells (PubMed:19365570). Retinal lens abnormalities develop progressively postnatally; at postnatal day 3 (P3) there is anterior lens vacuolization and liquefaction of lens cortical fibers (PubMed:19365570). At P24 there is evidence of extensive lens cortex vacuolation and early lens extrusion, progressing to extrusion of lens cortical material at P33 (PubMed:19365570).|||Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on integrin mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Within the complex, interacts (via SH2 domain) with PTPRA (when phosphorylated on 'Tyr-825') (PubMed:22801373). Interacts (via Ras-GEF domain) with BCAR1 (PubMed:10438950, PubMed:10896938, PubMed:12517963). Interacts (via Ras-GEF domain) with NEDD9 (PubMed:12517963, PubMed:19103205). Interacts with PTK2B/FAK1 (PubMed:10896938). Interacts with PTPN1. Interacts (via SH2 domain) with EGFR (when tyrosine-phosphorylated) (By similarity).|||Phosphorylated on tyrosine residues.|||The Ras-GEF domain appears to adopt a closed conformation rendering it incapable of carrying out canonical exchange factor function, this closed conformation is probably required for interaction with BCAR1.|||The SH2 domain mediates interaction with tyrosine-phosphorylated proteins (PubMed:10896938, PubMed:22801373). However, not involved in the binding to phosphorylated BCAR1 (PubMed:10896938). Required for cell cycle progression in response to INS/insulin (By similarity). Required for regulation of EGF-induced DNA synthesis (By similarity).|||The guanine nucleotide exchange factor (GEF) activity is controversial. One study showed GEF activity towards RALA, RAP1A and RRAS (PubMed:10896938). However, in another study, a construct containing only the Ras-GEF domain lacks GEF activity towards RAP1 (By similarity).|||Up-regulated by IL1A and LTA, in thymus cortical reticular cell lines.|||focal adhesion http://togogenome.org/gene/10090:Zkscan17 ^@ http://purl.uniprot.org/uniprot/Q5SXI5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||DNA-binding transcription factor that can both act as an activator and a repressor.|||Interacts (via zinc-fingers) with JARID2. Interacts with NSD1.|||Nucleus|||The C2H2-type zinc finger 1, also named C2HR, mediates the interaction with NSD1. http://togogenome.org/gene/10090:Sucla2 ^@ http://purl.uniprot.org/uniprot/Q9Z2I9 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.|||Belongs to the succinate/malate CoA ligase beta subunit family. ATP-specific subunit beta subfamily.|||Binds 1 Mg(2+) ion per subunit.|||Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for ATP. Interacts with ALAS2 (By similarity).|||Mitochondrion http://togogenome.org/gene/10090:Ehbp1l1 ^@ http://purl.uniprot.org/uniprot/Q99MS7 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Endosome|||Interacts with RAB8A, RAB8B, RAB10, RAB13 and RAB15 (in their GTP-bound forms); at least in case of RAB8A can bind 2 molecules of RAB8A simultaneously. Interacts with BIN1 and AMPH. Interacts with DNM1.|||May act as Rab effector protein and play a role in vesicle trafficking (By similarity). Involved in apical-directed transport in polarized epithelial cells; the functions seems to implicate Rab8, BIN1 and possibly DNM1 (PubMed:26833786).|||Prenylated (Probable). Farnelysation (predominant) and geranylgeranylation has been observed in vitro.|||Recycling endosome|||The CAAX motif is a signal for prenylation and required for endosomal colocalization with Rab8 and Rab10.|||The bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to Rab8, Rab10, Rab10, Rab13 and Rab15 (in their GTP-bound forms). http://togogenome.org/gene/10090:Taok1 ^@ http://purl.uniprot.org/uniprot/Q5F2E8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated (By similarity). Phosphorylated by ATM in response to DNA damage. Phosphorylated by LRRK2.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Proteolytically processed by caspase-3 (CASP3).|||Self-associates. Interacts with MAP2K3. Interacts with SPRED1 (By similarity). Interacts with TESK1; the interaction inhibits TAOK1 kinase activity (By similarity). Interacts with MAP3K7 (By similarity).|||Serine/threonine-protein kinase activity is inhibited by SPRED1.|||Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade (By similarity). During fetal development, it plays an essential role in the regulation of neuronal differentiation and migration to the cortical plate (PubMed:33565190). http://togogenome.org/gene/10090:Osbpl1a ^@ http://purl.uniprot.org/uniprot/Q3V156|||http://purl.uniprot.org/uniprot/Q91XL9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OSBP family.|||Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate. Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A. Binds 25-hydroxycholesterol and cholesterol.|||Interacts (via FFAT motif) with VAPA and VAPB (By similarity). Interacts with the GTP-bound form of RAB7A (By similarity). Interacts with OAS1B (PubMed:22623793). Interacts (via FFAT motif) with MOSPD2 (via MSP domain) (By similarity).|||Late endosome|||The FFAT motif is required for interaction with MOSPD2, VAPA and VAPB.|||The FFAT motif is required for interaction with MOSPD2.|||Ubiquitous. http://togogenome.org/gene/10090:Snx16 ^@ http://purl.uniprot.org/uniprot/Q8C080 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the sorting nexin family.|||Cytoplasm|||Early endosome membrane|||Homooligomer. Interacts with EGFR (By similarity).|||Late endosome membrane|||Lysosome|||May be involved in several stages of intracellular trafficking. Plays a role in protein transport from early to late endosomes. Plays a role in protein transport to the lysosome. Promotes degradation of EGFR after EGF signaling (By similarity).|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate. http://togogenome.org/gene/10090:Dnah9 ^@ http://purl.uniprot.org/uniprot/B1AR51 ^@ Similarity ^@ Belongs to the dynein heavy chain family. http://togogenome.org/gene/10090:Cnnm3 ^@ http://purl.uniprot.org/uniprot/Q32NY4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ACDP family.|||Cell membrane|||Probable metal transporter.|||Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo.|||Widely expressed with highest levels in brain, kidney, liver, lung and heart. http://togogenome.org/gene/10090:Vcpkmt ^@ http://purl.uniprot.org/uniprot/Q8C436 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the methyltransferase superfamily. METTL21 family.|||Cytoplasm|||Deficient mice are viable, fertile and have no obvious pathological phenotype.|||Interacts with ALKBH6. Interacts with ASPSCR1 and UBXN6; interaction with ASPSCR1, but not with UBXN6, enhances VCP methylation.|||Protein N-lysine methyltransferase that specifically trimethylates 'Lys-315' of VCP/p97; this modification may decrease VCP ATPase activity.|||Widely expressed. http://togogenome.org/gene/10090:Pgrmc2 ^@ http://purl.uniprot.org/uniprot/Q80UU9 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adipose tissue-specific knockout mice adapted to 30 degrees Celsius show no difference in body weight or white adipose tissue (WAT) mass but have reduced brown adipose tissue (BAT) weight relative to their wild-type littermates. BAT loses its distinctive reddish color. In contrast to wild-type mice, which activate thermogenesis and preserve body temperature when exposed to cold (4 degrees Celsius), mutants rapidly become hypothermic and die if not rescued. They have a total heme content reduced of about 60%. Mutants housed at room temperature and fed a high-fat diet (HFD) show no differences in body weight or composition, except for decreased BAT mass. However, they have higher fasting glycaemia and decreased glucose tolerance and insulin sensitivity. They also exhibit hyperlipidaemia and exacerbated liver steatosis with about 70% more triglycerides (PubMed:31748741). Conditional knockout from female reproductive tissues results in postimplantation embryonic death leading to subfertility, with female mice producing 47% fewer pups/litter than wild-types. They undergo premature reproductive senescence by parities 2 to 5, producing 37.8% fewer litters overall during the trial compared with wild-types (PubMed:28005395). Double conditional knockout for PGRMC1 and PGRMC2 from female reproductive tissues results in postimplantation embryonic death leading to subfertility, with female mice producing fewer pups/litter than wild-types. They undergo premature reproductive senescence, producing fewer litters overall during the trial compared with wild-types (PubMed:28005395).|||Belongs to the cytochrome b5 family. MAPR subfamily.|||Endoplasmic reticulum|||Expressed in brown adipose tissue, white adipose tissue, liver, heart, skeletal muscle, brain and adrenal gland.|||Interacts with PGRMC1 (PubMed:31748741). Interacts with AAAS (By similarity).|||Membrane|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Nucleus envelope|||Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan (PubMed:28005395). May serve as a universal non-classical progesterone receptor in the uterus (Probable). Intracellular heme chaperone required for delivery of labile, or signaling heme, to the nucleus. Plays a role in adipocyte function and systemic glucose homeostasis. In brown fat, which has a high demand for heme, delivery of labile heme in the nucleus regulates the activity of heme-responsive transcriptional repressors such as NR1D1 and BACH1 (PubMed:31748741).|||The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 131 and 155. http://togogenome.org/gene/10090:Tmsb15b2 ^@ http://purl.uniprot.org/uniprot/A2AF31 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the thymosin beta family.|||Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.|||cytoskeleton http://togogenome.org/gene/10090:Ttll6 ^@ http://purl.uniprot.org/uniprot/A4Q9E8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tubulin--tyrosine ligase family.|||Cytoplasm|||Found in a complex with CEP41.|||Gln-180 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.|||Highly expressed in testis (PubMed:17499049). Expressed in brain, heart, kidney, liver, lung, muscle and trachea (PubMed:17499049). In the brain, specifically expressed in ependymal cilia (PubMed:23897886).|||Polyglutamylase which modifies both tubulin and non-tubulin proteins, generating alpha-linked polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues of target proteins (PubMed:17499049, PubMed:21074048, PubMed:20530212, PubMed:26829768, PubMed:32747782). Preferentially mediates ATP-dependent long polyglutamate chain elongation over the initiation step of the polyglutamylation reaction (PubMed:17499049, PubMed:21074048, PubMed:20530212, PubMed:26829768, PubMed:32747782). Preferentially modifies the alpha-tubulin tail over a beta-tail (PubMed:17499049, PubMed:20530212, PubMed:21074048, PubMed:32747782). Promotes tubulin polyglutamylation which stimulates spastin/SPAST-mediated microtubule severing, thereby regulating microtubule functions (PubMed:20530212). Mediates microtubule polyglutamylation in primary cilia axoneme which is important for ciliary structural formation and motility (PubMed:22246503). Mediates microtubule polyglutamylation in motile cilia, necessary for the regulation of ciliary coordinated beating (PubMed:23897886). Polyglutamylates non-tubulin protein nucleotidyltransferase CGAS, leading to CGAS DNA-binding inhibition, thereby preventing antiviral defense response (PubMed:26829768).|||The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.|||cilium axoneme|||cilium basal body|||cytoskeleton http://togogenome.org/gene/10090:Adad2 ^@ http://purl.uniprot.org/uniprot/Q9D5P4 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ADAD family.|||Cytoplasm|||Male mice are sterile and show defects in germ-cell development.|||Nucleus|||Required for male fertility and normal male germ cell differentiation.|||Testis-specific (at protein level). http://togogenome.org/gene/10090:Tmem253 ^@ http://purl.uniprot.org/uniprot/Q3UNB8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Mill2 ^@ http://purl.uniprot.org/uniprot/Q8HWE5 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MHC class I family.|||Binds to heparan sulfate proteoglycans on the surface of fibroblast (NIH-3T3) cells.|||Cell membrane|||Heterodimer with B2M (beta-2-microglobulin).|||Lacks key residues involved in peptide docking and also does not require TAP (transporter involved in antigen processing) for cell surface expression, suggesting that this is a non-classical MHC class I protein which does not play a role in antigen presentation.|||N-glycosylated.|||Ubiquitously expressed in neonatal and adult tissues. http://togogenome.org/gene/10090:Gnl3 ^@ http://purl.uniprot.org/uniprot/Q8CI11 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class YlqF/YawG GTPase family.|||Expressed at 8.5 dpc and 10.5 dpc in the cerebral cortex; expression declines rapidly from this point.|||Expressed in the adult bone marrow population that is enriched in hematopoietic stem cells.|||In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.|||Interacts with MDM2; this interaction stabilizes MDM2 (PubMed:21132010). Interaction with MDM2 occurs in the nucleoplasm and is triggered by a nucleolar release mechanism, such as mitosis-induced nucleolar disassembly (PubMed:21132010). Indirectly interacts with TP53, via MDM2-binding (By similarity). Interacts with TSC22D1 isoform 2 (By similarity).|||May be required to maintain the proliferative capacity of stem cells (By similarity). Stabilizes MDM2 by preventing its ubiquitination, and hence proteasomal degradation.|||Nucleus|||The basic domain (B) allows nucleolar localization in the absence of GTP. The intermediate domain (I) inhibits nucleolar localization by the B domain and is required for exit from the nucleolus. Exit from the nucleolus to the nucleoplasm requires both the I and the acidic (A) domains, and may be triggered by GTP hydrolysis (By similarity).|||nucleolus http://togogenome.org/gene/10090:Arfip2 ^@ http://purl.uniprot.org/uniprot/Q8K221 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Forms homodimers or heterodimers with ARFIP1. Interacts with RAC1. Specifically binds to GTP-bound ARF1 and ARF6, but binds to RAC1.GTP and RAC1.GDP with similar affinities. Interacts with ARL1. Interacts (via N-terminus) with IKBKB and IKBKG; these interactions inhibit activation of NF-kappa-B.|||Golgi apparatus|||Plays a role in constitutive metalloproteinase (MMP) secretion from the trans Golgi network. May have important functions during vesicle biogenesis at certain cargo subdomains, which could be predominantly utilized by secreted MMPs, such as MMP7 and MMP2. Also involved in autophagy by regulating the starvation-dependent trafficking of ATG9A vesicles which deliver the phosphatidylinositol 4-kinase beta (PI4KB) to the autophagosome initiation site. Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria. In addition, plays a role in NF-kappa-B inhibition by interacting with IKBKB and IKBKG.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Taar6 ^@ http://purl.uniprot.org/uniprot/Q5QD13 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Orphan olfactory receptor specific for trace amines.|||Specifically expressed in neurons of the olfactory epithelium, to discrete glomeruli predominantly localized to a confined bulb region. Present in a ventral area of the main olfactory epithelium. http://togogenome.org/gene/10090:Gpr161 ^@ http://purl.uniprot.org/uniprot/A0A140T8Q9|||http://purl.uniprot.org/uniprot/B2RPY5 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ An intragenic deletion in Gpr161 is responsible for the vacuolated lens (vl) phenotype that is characterized by neural tube defects and congenital cataracts. The vl mutation aroses spontaneously. About half of vl/vl embryos display lumbar-sacral spina bifida and die before birth, and the other half have closed neural tubes but show thinning of the midline neuroepithelium and epidermis, dilation of the dorsal ventricle, and presence of ectopic neuroepithelial cells in the ventricle. All surviving adults display congenital cataracts (PubMed:18250320). It is not a null mutant allele (PubMed:23332756).|||Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Embryonic lethality by 10.5 dpc caused by increased Shh signaling and ventralization throughout the developing neural tube. Defects in Gli3 processing.|||Expressed ubiquitously from 8.5 dpc and is mostly concentrated in the developing nervous system at later stages. By 10.5 dpc, it is mainly expressed in the neural tube. At later embryonic stages (12.5 dpc and 15.5 dpc), it is predominantly expressed in the brain, spinal cord, and dorsal ganglia and weakly expressed in the hindlimb. According to PubMed:18250320, expression is restricted to the lateral neural folds, while PubMed:23332756 detects expression throughout the neural tube. Also expressed at low levels in kidney stroma and retina at 15.5 dpc.|||Key negative regulator of Shh signaling, which promotes the processing of GLI3 into GLI3R during neural tube development. Recruited by TULP3 and the IFT-A complex to primary cilia and acts as a regulator of the PKA-dependent basal repression machinery in Shh signaling by increasing cAMP levels, leading to promote the PKA-dependent processing of GLI3 into GLI3R and repress the Shh signaling. In presence of SHH, it is removed from primary cilia and is internalized into recycling endosomes, preventing its activity and allowing activation of the Shh signaling. Its ligand is unknown.|||Membrane|||cilium membrane http://togogenome.org/gene/10090:Mpped1 ^@ http://purl.uniprot.org/uniprot/Q91ZG2 ^@ Function|||Similarity ^@ Belongs to the UPF0046 family.|||May have metallophosphoesterase activity (in vitro). http://togogenome.org/gene/10090:Mboat1 ^@ http://purl.uniprot.org/uniprot/Q8BH98 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acyltransferase which catalyzes the transfer of an acyl group from an acyl-CoA towards a lysophospholipid producing a phospholipid and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle (PubMed:18287005). Acts on lysophosphatidylserine (1-acyl-2-hydroxy-sn-glycero-3-phospho-L-serine or LPS) and lysophosphatidylethanolamine (1-acyl-sn-glycero-3-phosphoethanolamine or LPE), and to a lesser extend lysophosphatidylcholine (PubMed:18287005). Prefers oleoyl-CoA as the acyl donor and 1-oleoyl-LPE as acceptor (PubMed:18287005). May play a role in neurite outgrowth during neuronal differentiation (PubMed:27048541).|||Belongs to the membrane-bound acyltransferase family.|||Endoplasmic reticulum|||Highly expressed in stomach, epididymis, and colon.|||Membrane http://togogenome.org/gene/10090:Zfp59 ^@ http://purl.uniprot.org/uniprot/P16373 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed predominantly in the testis (at protein level).|||Expression is positively regulated upon differentiation. Is specifically synthesized during postmeiotic phase of male germline differentiation.|||May have a role during differentiation processes.|||Nucleus|||Several sequencing errors. http://togogenome.org/gene/10090:Gpr25 ^@ http://purl.uniprot.org/uniprot/P0C5I1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Membrane|||Orphan receptor. http://togogenome.org/gene/10090:Lsm14b ^@ http://purl.uniprot.org/uniprot/Q8CGC4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the LSM14 family.|||Component of a ribonucleoprotein (RNP) complex. Interacts with DDX6.|||Required for oocyte meiotic maturation (PubMed:28458300). May be involved in the storage of translationally inactive mRNAs and protect them from degradation (PubMed:28458300). Plays a role in control of mRNA translation (By similarity). http://togogenome.org/gene/10090:Lrrc18 ^@ http://purl.uniprot.org/uniprot/Q9CQ07 ^@ Function|||Induction|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Contaminating sequence. Potential poly-A sequence.|||Cytoplasm|||Exclusively expressed in spermatocytes and roud spermatids within seminiferous tubules during spermatogenesis.|||May be involved in the regulation of spermatogenesis and sperm maturation.|||Up-regulated during sexual maturation and dowm-regulated by experimental cryptorchidism and heat stress. http://togogenome.org/gene/10090:Tmem132b ^@ http://purl.uniprot.org/uniprot/F7BAB2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM132 family.|||Membrane http://togogenome.org/gene/10090:Dcun1d1 ^@ http://purl.uniprot.org/uniprot/Q9QZ73 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in the developing forebrain, midbrain and hindbrain at early stages of neuronal development.|||Highly expressed in testis. Also expressed in brain, heart, liver, skeletal muscle and kidney. In brain, preferentially expressed in the telencephalon ventricular and subventricular zones, albeit at low levels. In adult testis, expressed in cells above seminiferous tubules, but only weakly in spermatogonia.|||Mono- and poly-ubiquitinated by ARIH2 and ARIH1. Monoubiquitination by ARIH2 is mediated by an interaction between autoubiquitinated ARIH2 and the UBA-like domain. The monoubiquitinated form preferentially interacts with non-neddylated cullins and modulates cullin RING ligase (CRL) complex composition and activity.|||Nucleus|||Part of an E3 complex for neddylation composed of cullins, RBX1, UBE2M and CAND1. Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction. Binds neddylated CUL1. Interacts (via the C-terminus 50 AA) directly with RBX1. Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F. Interacts preferentially with UBE2M-NEDD8 thioester (via N-terminus 1-26 AA) than with free UBE2M. UBE2M N-terminal acetylation increases the affinity of this interaction by about 2 orders of magnitude. Interacts with CAND1; this interaction is indirect and is bridged by cullins such as CUL1 and CUL3. May also interact with regulators or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these interactions are bridged by cullins. Component of VCB complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation. Interacts with VHL; this interaction triggers engagement of HIF1A in the VCB complex and is independent of CUL2. Interacts with CUL2 independently of VHL. Interacts with SOCS1 and SOCS2. Interacts with HIF1A; this interaction increases the interaction between VHL and DCUN1D1. Interacts (via UBA-like domain) with ARIH2; promotes DCUN1D1 ubiquitination.|||Part of an E3 ubiquitin ligase complex for neddylation. Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (By similarity). Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (By similarity). Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (PubMed:20563250).|||The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins. The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction affinities. The UBA-like domain mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin ligation to DCUN1D1. http://togogenome.org/gene/10090:Lcor ^@ http://purl.uniprot.org/uniprot/A4FTY7|||http://purl.uniprot.org/uniprot/Q6ZPI3 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in heart and kidney.|||Interacts with ESR1 and ESR2 in the presence of estradiol. Interacts with CTBP1, HDAC3 and HDAC6. Component of a large corepressor complex that contains about 20 proteins, including CTBP1, CTBP2, HDAC1 and HDAC2 (By similarity).|||Nucleus|||Repressor of ligand-dependent transcription activation by various nuclear repressors. Repressor of ligand-dependent transcription activation by ESR1, ESR2, NR3C1, PGR, RARA, RARB, RARG, RXRA and VDR (By similarity). May act as transcription activator that binds DNA elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'. http://togogenome.org/gene/10090:Or8g27 ^@ http://purl.uniprot.org/uniprot/Q9EQ91 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem39a ^@ http://purl.uniprot.org/uniprot/Q9CYC3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TMEM39 family.|||Endoplasmic reticulum membrane|||Interacts with SACM1L, SEC23A and SEC24A.|||Regulates autophagy by controlling the spatial distribution and levels of the intracellular phosphatidylinositol 4-phosphate (PtdIns(4)P) pools (By similarity). Modulates (PtdIns(4)P) levels by regulating the ER-to-Golgi trafficking of the phosphatidylinositide phosphatase SACM1L (By similarity). http://togogenome.org/gene/10090:Lrp1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0I9|||http://purl.uniprot.org/uniprot/Q3U454|||http://purl.uniprot.org/uniprot/Q91ZX7 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) Functions as a receptor for Vibrio cholerae cholix toxin and for Pseudomonas aeruginosa exotoxin A.|||Belongs to the LDLR family.|||Cell membrane|||Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non-covalently associated. Gamma-secretase-dependent cleavage of LRP-85 releases the intracellular domain from the membrane (By similarity).|||Cytoplasm|||Death during early embryogenesis around 14 dpc.|||Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development (PubMed:1423604). Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Acts as an alpha-2-macroglobulin receptor (By similarity). Acts as TAU/MAPT receptor and controls the endocytosis of TAU/MAPT as well as its subsequent spread (PubMed:32296178). May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission (By similarity).|||Golgi outpost|||Heterodimer of an 85-kDa membrane-bound carboxyl subunit and a non-covalently attached 515-kDa N-terminal subunit. Intracellular domain interacts with MAFB (PubMed:15135046). Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with SNX17, PID1/PCLI1, PDGF and CUBN. The intracellular domain interacts with SHC1, GULP1 and DAB1 (By similarity). Can weakly interact (via NPXY motif) with DAB2 (via PID domain); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif (PubMed:11247302). Interacts with MDK; promotes neuronal survival (PubMed:10772929). Interacts with LRPAP1; this interaction is followed by rapid internalization. Interacts with uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each other, leading to rapid endocytosis; this interaction is abolished in the presence of LRPAP1/RAP. Also interacts with tPA/PLAT alone or in complex with SERPINE1. Interacts with the urokinase receptor PLAUR; this interaction leads to PLAUR internalization and is impaired in the presence of SORL1. Interacts with PDGFB. Interacts with TAU/MAPT, leading to endocytosis; this interaction is reduced in the presence of LRPAP1/RAP (By similarity).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Nucleus|||Phosphorylated on serine and threonine residues.|||Phosphorylated on tyrosine residues upon stimulation with PDGF. Tyrosine phosphorylation promotes interaction with SHC1 (By similarity).|||coated pit|||microtubule organizing center http://togogenome.org/gene/10090:Ace3 ^@ http://purl.uniprot.org/uniprot/D0G895 ^@ Caution|||Disruption Phenotype|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M2 family.|||Expressed in sperm and testis (at protein level) (PubMed:20421979). Expressed in heart and testis (PubMed:17597519). Not detected in kidney, lung, liver, brain, ovary, spleen and thymus (PubMed:17597519, PubMed:20421979).|||Interacts with IZUMO1.|||Lacks the conserved Glu residue in position 378 necessary for the catalytic activity.|||No visible phenotype. Sperm have normal fertilizing ability.|||acrosome membrane http://togogenome.org/gene/10090:L2hgdh ^@ http://purl.uniprot.org/uniprot/Q91YP0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the L2HGDH family.|||Mitochondrion http://togogenome.org/gene/10090:Vamp1 ^@ http://purl.uniprot.org/uniprot/Q62442 ^@ Disease Annotation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type X (BoNT/X) which hydrolyzes the 68-Arg-|-Ala-69 bond and probably inhibits neurotransmitter release (PubMed:28770820). It remains unknown whether BoNT/X is ever produced, or what organisms it targets.|||Belongs to the synaptobrevin family.|||Cytoplasmic vesicle membrane|||Defects in Vamp1 are the cause of lethal-wasting (lew) phenotype, a mice mutant strain. The lew mutant phenotype is inherited in an autosomal recessive manner and manifests with neurological signs. Lew animals are characterized by a general lack of movement and wasting, eventually leading to death before weaning. The affected animals die near postnatal day 15 (P15). By P10, the mutants are noticeably immobile and lay on their side. Before this stage, mutants can be identified by a failure to attempt to right themselves. In earlier perinatal stages, the mutants are of normal size and difficult to discern from their normal littermates. The affected mice can move their limbs although not in any purposeful manner. No protein is detectable in homozygous mutant animals.|||Highly expressed in the zona incerta and rostral periolivary region of the brain. Other neuroanatomical regions show negligible expression. Expressed in the retina, expression observed in the outer segments of the photoreceptors, in the outer and inner plexiform layers, and in a subset of ganglion cells.|||Interacts with VAPA and VAPB.|||Involved in the targeting and/or fusion of transport vesicles to their target membrane.|||synaptic vesicle membrane|||synaptosome http://togogenome.org/gene/10090:Dmtn ^@ http://purl.uniprot.org/uniprot/Q9WV69 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the villin/gelsolin family.|||Both the N-terminal core domain and the C-terminal headpiece domain are sufficient for binding to F-actin and necessary for actin bundling activity.|||Cell membrane|||Cell projection|||Cytoplasm|||Endomembrane system|||Expressed in platelets. Isoform 1 and isoform 2 are expressed in mature erythrocytes (at protein level).|||Membrane|||Membrane-cytoskeleton-associated protein with F-actin-binding activity that induces F-actin bundles formation and stabilization. Its F-actin-bundling activity is reversibly regulated upon its phosphorylation by the cAMP-dependent protein kinase A (PKA). Binds to the erythrocyte membrane glucose transporter-1 SLC2A1/GLUT1, and hence stabilizes and attaches the spectrin-actin network to the erythrocytic plasma membrane. Plays a role in maintaining the functional integrity of PKA-activated erythrocyte shape and the membrane mechanical properties. Also plays a role as a modulator of actin dynamics in fibroblasts; acts as negative regulator of the RhoA activation pathway. In platelets, functions as a regulator of internal calcium mobilization across the dense tubular system that affects platelet granule secretion pathways and aggregation. Also required for the formation of a diverse set of cell protrusions, such as filopodia and lamellipodia, necessary for platelet cell spreading, motility and migration. Acts as a tumor suppressor and inhibits malignant cell transformation.|||Mice are viable and born at the expected Mendelian ratio. Adult mice show compensated anemia and display mild microcytosis and spherocytosis. The erythrocyte plasma membrane association with the spectrin-actin skeleton is fragile and mechanically unstable.|||Monomeric (isoform 2); under reducing conditions. Self-associates. Exists under oxidizing condition as a trimer of two isoforms 2 and isoform 1 linked by disulfide bonds (Probable). Found in a complex with DMTN, F-actin and spectrin. Found in a complex with ADD2, DMTN and SLC2A1. Interacts with F-actin, ITPKB and spectrin. Isoform 2 interacts with SLC2A1 (via C-terminus cytoplasmic region) (By similarity). Interacts with RASGRF2.|||Phosphorylated. Phosphorylation at Ser-403 by PKA causes the C-terminal headpiece domain to associate with the N-terminal core domain, and leads to the inhibition of its actin bundling activity (By similarity).|||cytoskeleton|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Cnih3 ^@ http://purl.uniprot.org/uniprot/G3XA11|||http://purl.uniprot.org/uniprot/Q6ZWS4|||http://purl.uniprot.org/uniprot/Q9D6E1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity).|||Belongs to the cornichon family.|||Membrane|||Postsynaptic cell membrane|||Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by regulating their rates of activation, deactivation and desensitization (By similarity). http://togogenome.org/gene/10090:Mansc1 ^@ http://purl.uniprot.org/uniprot/Q9CR33 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Nectin4 ^@ http://purl.uniprot.org/uniprot/Q8R007 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nectin family.|||Cell membrane|||Detected at embryonic days 11, 15 and 17.|||Expressed in brain, lung, testis and embryo.|||Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1.|||Self-associates. Interacts via its Ig-like V-type domain with NECTIN1 Ig-like V-type domain. Interacts via its C-terminus with AFDN (By similarity).|||adherens junction http://togogenome.org/gene/10090:Zdhhc13 ^@ http://purl.uniprot.org/uniprot/Q9CWU2 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DHHC palmitoyltransferase family. AKR/ZDHHC17 subfamily.|||Cytoplasmic vesicle membrane|||Expressed in most adult tissues, but at low levels in the liver, skin, and lung.|||Expressed most highly in the liver, lung, and brain at posnatal day 2 (P2). In contrast, expressed most highly in skin at P8 in the epithelium surrounding the hair follicles.|||Golgi apparatus membrane|||Interacts (via ANK repeats) with CLIP3 (PubMed:26198635). Interacts (via ANK repeats) with DNAJC5 (via C-terminus) (PubMed:25253725, PubMed:26198635). Interacts (via ANK repeats) with HTT (PubMed:26198635). Interacts (via ANK repeats) with MAP6 (PubMed:26198635). Interacts (via ANK repeats) with SNAP23 (PubMed:26198635). Interacts (via ANK repeats) with SNAP25 (PubMed:25253725, PubMed:26198635). May interact (via ANK repeats) with SPRED2 (PubMed:28882895).|||Knockdown of the expression in mice through ENU-induced stop codon in the gene or targeted knockout of the gene result is similar phenotypes (PubMed:20548961). Mutant mice are normal at birth, but by postnatal day 7 appear smaller (PubMed:20548961). They display generalized hypotrichosis and hair loss with altered skin that is loose with wrinkling and folding (PubMed:20548961). Kyphosis and osteoporosisis are also observed (PubMed:20548961). Finally, a generalized amyloid deposition results in early death (PubMed:20548961).|||Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates (PubMed:18794299, PubMed:19299482). Palmitoyltransferase for HTT and GAD2 (PubMed:19299482, PubMed:20548961). May play a role in Mg(2+) transport (PubMed:18794299).|||The DHHC domain is required for palmitoyltransferase activity.|||Up-regulated by low extracellular Mg(2+). http://togogenome.org/gene/10090:Ifi204 ^@ http://purl.uniprot.org/uniprot/P0DOV2 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated upon bacterial infection, leading to translocation from nucleus to cytoplasm and subsequent recruitment of STING to activate IFN-beta production.|||Belongs to the HIN-200 family.|||By beta interferon. By macrophage differentiation factors. During myocyte differentiation. By different bacterial infections such as Staphylococcus aureus or Mycobacterium bovis.|||Cytoplasm|||Deletion mutant mice display increased susceptibility to Staphylococcus aureus pulmonary infection.|||Interacts with UBTF. Interacts with RUNX2. Interacts with ID1, ID2 and ID3. Interacts with STING (PubMed:28529930).|||Interferon-stimulated protein that plays a role in several biological processes including cell differentiation, autophagy and innate immunity (PubMed:16244109, PubMed:25710914, PubMed:30936875). Cooperates with CGAS to sense dsDNA and activates the STING-dependent type I IFN pathway (PubMed:25710914, PubMed:33619523). Mechanistically, gets acteylated upon bacterial infection and then translocates from nucleus into cytoplasm to recruit STING for activation of TBK1-dependent IRF3 nuclear translocation and IFN-beta release (PubMed:28529930). Inhibits the transcription of ribosomal RNA. May inhibit DNA binding by UBTF. Inhibits cell growth via p53/TP53 and RB1-dependent and independent pathways. Acts as a coactivator of RUNX2 during osteogenesis. May be involved in macrophage differentiation. Enables skeletal muscle and cardiac myocyte differentiation by sequestring Id proteins in the cytosol and promoting their ubiquitination and subsequent degradation.|||Nucleus|||Present in osteoblasts (at protein level).|||The 2 HIN-200 domains are able to interact with RUNX2.|||nucleolus http://togogenome.org/gene/10090:Cyp2b23 ^@ http://purl.uniprot.org/uniprot/E9Q593 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cytochrome P450 family.|||Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Lnpk ^@ http://purl.uniprot.org/uniprot/A2ASL8|||http://purl.uniprot.org/uniprot/Q7TQ95 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the lunapark family.|||Endoplasmic reticulum (ER)-shaping membrane protein that plays a role in determining ER morphology. Involved in the stabilization of nascent three-way ER tubular junctions within the ER network. May also play a role as a curvature-stabilizing protein within three-way ER tubular junction network. May be involved in limb and central nervous system development (PubMed:12732147).|||Endoplasmic reticulum membrane|||Expressed in most tissues at basal level, with reinforcement in distal limb buds, genital bud, and in parts of the central nervous system.|||Homodimer; homodimerization requires the C4-type zinc finger motif and decreases during mitosis in a phosphorylation-dependent manner.|||Myristoylated; myristoylation is necessary for the endoplasmic reticulum (ER) three-way ER tubular junction formation, but is not required neither for membrane translocation, membrane topology formation, nor for the specific localization to ER membranes.|||Phosphorylated. Phosphorylation occurs at Ser-177, Ser-182, Ser-222, Ser-316 and Ser-380 during interphase. Phosphorylation occurs at Ser-114, Ser-153, Ser-194, Thr-211 and Ser-348 during mitosis; these phosphorylations reduce both its homodimerization and the ER three-way tubular junction formation.|||Plays a role in determining ER morphology.|||Strongly expressed in both limb and genital buds as is the case for Evx2 and Hoxd genes, in particular Hoxd13. In developing limb buds, it is first seen in 10.5 days old fetuses, in the posterior distal bud, to subsequently extend throughout the distal aspect, in presumptive digits.|||Subject to proteasomal degradation following phosphorylation during mitosis.|||The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation.|||The transmembrane domain 1 and 2 function as a signal-anchor and stop-transfer sequence, respectively, generating a double-spanning integral membrane protein with a N- and C-terminal cytoplasmic orientation. Transmembrane domain 1 and 2 are probably sufficient to mediate membrane translocation and topology formation in a N-myristoylation-independent manner. Transmembrane domain 2 is sufficient to block the protein secretion pathway. The two coiled-coil domains are necessary for its endoplasmic reticulum (ER) three-way tubular junction localization. The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation.|||Was named 'Lunapark' because the protein sequence contains the word 'LNPARK'. http://togogenome.org/gene/10090:Kcnj11 ^@ http://purl.uniprot.org/uniprot/Q61743 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily.|||Interacts with ABCC9/SUR2 (By similarity). Interacts with ABCC8/SUR.|||Membrane|||Phosphorylation by MAPK1 results in changes in channel gating that destabilize the closed states and reduce the ATP sensitivity.|||This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium. Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation (By similarity). http://togogenome.org/gene/10090:Wbp11 ^@ http://purl.uniprot.org/uniprot/Q923D5 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates pre-mRNA splicing. May inhibit PP1 phosphatase activity.|||Cytoplasm|||Interacts via the PGR motif with PQBP1 in the nucleus. Interacts with the WW domains of WBP4 (By similarity). Interacts with PPP1CA, PPP1CB and PPP1CC.|||Mutant embryos die prior to 8.5 dpc (PubMed:33276377). Heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus (PubMed:33276377).|||Nucleus|||Ubiquitously expressed, with highest levels in testis. http://togogenome.org/gene/10090:Apoa1 ^@ http://purl.uniprot.org/uniprot/Q00623 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the apolipoprotein A1/A4/E family.|||Glycosylated.|||Homodimer (By similarity). Interacts with APOA1BP and CLU. Component of a sperm activating protein complex (SPAP), consisting of APOA1, an immunoglobulin heavy chain, an immunoglobulin light chain and albumin. Interacts with NDRG1. Interacts with SCGB3A2 (By similarity). Interacts with NAXE and YJEFN3 (By similarity).|||Major protein of plasma HDL, also found in chylomicrons.|||May be acylated.|||Palmitoylated.|||Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility.|||Phosphorylation sites are present in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Cldn3 ^@ http://purl.uniprot.org/uniprot/Q545A5|||http://purl.uniprot.org/uniprot/Q9Z0G9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with Clostridium perfringens enterotoxin CPE; the interaction may disrupt claudin assembly in tight junctions.|||Belongs to the claudin family.|||Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN1 and CLDN2 homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.|||Cell membrane|||Expressed in the lung (PubMed:9892664, PubMed:24588076). Expressed at high levels in the liver and at lower levels, in kidney and testis (PubMed:9892664).|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||tight junction http://togogenome.org/gene/10090:Emilin2 ^@ http://purl.uniprot.org/uniprot/Q8K482 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highest levels are present in cochlea of P8 pups, followed by modest levels in adult heart and lung, and much lower levels in forebrain, brainstem, cerebellum and hypothalamus. Very low levels detected in muscle, liver, kidney and eye.|||Homotrimer associated through a moderately stable interaction of the C-terminal globular C1q domains, allowing the nucleation of the triple helix and then a further quaternary assembly to higher-order polymers via intermolecular disulfide bonds (By similarity). Interacts with EMILIN1.|||Low levels detected in cochlea in neonatal pups at P1. Levels increased 2-fold by P5 and rose further to 16-fold at P13. Expression declined somewhat in adult mice. At 9.5 dpc, as during all stages of development, it is strongly expressed in the neural fold, the limbbuds and the heart.|||May be responsible for anchoring smooth muscle cells to elastic fibers, and may be involved not only in the formation of the elastic fiber, but also in the processes that regulate vessel assembly. Has cell adhesive capacity. Major component of the cochlear basilar membrane (BM) which may contribute to the developmental assembly or function of the BM.|||extracellular matrix http://togogenome.org/gene/10090:Hs2st1 ^@ http://purl.uniprot.org/uniprot/Q8R3H7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 7.5 dpc, it is expressed in all three germ layers, although it appears to be more expressed in the embryonic ectoderm and the node. Widespread expression persists at 8.5 dpc, although it is clearly expressed at higher level in rhombomeres 2 and 4 and branchial arches 1 and 2 (which are populated by neural crest from these rhombomeres). At 10.5 dpc, the dorsal and ventral aspects of the neural tube, brain and midbrain-hindbrain junction show the most intense expression. A day later in development, elevated expression is found in the floor plate and the sclerotome. At 12.5 dpc, both the floor plate and the roofplate exhibit strong expression as the mesenchyme of the limb and of the developing whisker follicles. At 13.5 dpc, it is predominantly expressed in embryonic mesenchyme, especially at sites of epithelial-mesenchymal interactions such as the developing teeth and whisker follicles. Strong expression is also apparent in the perichondria of the cartilaginous skeleton, an important site for the regulation of skeletal differentiation.|||Belongs to the sulfotransferase 3 family.|||Catalyzes the transfer of sulfate to the C2-position of selected hexuronic acid residues within the maturing heparan sulfate (HS). 2-O-sulfation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high-affinity ligand-binding interactions and signaling processes. Required for metanephric development of kidney formation, suggesting that 2-O-sulfation within HS is essential for signaling between ureteric bud and metanephric mesenchyme. Mediates 2-O-sulfation of both L-iduronyl and D-glucuronyl residues.|||Golgi apparatus membrane|||Homotrimer (By similarity). Interacts with the C5-epimerase GLCE.|||Mice die in the neonatal period, exhibiting bilateral renal agenesis and defects of the eye and the skeleton. Uronate 2-O-sulfates are not detected in such mice, however, the domain structure of the HS is conserved, due to a compensatory increase in N- and 6-O-sulfation maintain the overall charge density.|||N-glycosylated.|||Widely expressed. Expressed at higher level in lung and brain. Weakly expressed in spleen. http://togogenome.org/gene/10090:Akr1b3 ^@ http://purl.uniprot.org/uniprot/P45376|||http://purl.uniprot.org/uniprot/Q3UDY1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundant in the testis, skeletal muscle and kidney.|||Belongs to the aldo/keto reductase family.|||Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:17381426, PubMed:19010934, PubMed:7851421). Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia. Reduces steroids and their derivatives and prostaglandins (PubMed:19010934). Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal. Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (By similarity).|||Cytoplasm|||Deficient mice have no apparent developmental or reproductive abnormality except a defect in their urine-concentrating ability, which resulted in polyuria and polydipsia.|||Monomer. http://togogenome.org/gene/10090:Csrp2 ^@ http://purl.uniprot.org/uniprot/P97314 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Drastically down-regulated in response to PDGF-BB or cell injury, that promote smooth muscle cell proliferation and dedifferentiation. Seems to play a role in the development of the embryonic vascular system (By similarity).|||Interacts with KAT14. The LIM domain 1 is necessary and sufficient for this interaction (By similarity). Interacts with GLRX3.|||Nucleus http://togogenome.org/gene/10090:Efcab9 ^@ http://purl.uniprot.org/uniprot/Q9DAM2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation (PubMed:34225353, PubMed:31056283). pH-dependent Ca(2+) sensor required to activate the CatSper channel (PubMed:31056283). Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization (PubMed:31056283). Associates with the CatSper complex via direct interaction with CATSPERZ, and senses intracellular Ca(2+) (PubMed:31056283). Together with CATSPERZ, associates with the CatSper channel pore and is required for the two-row structure of each single CatSper channel (PubMed:31056283).|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG2, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (Probable). Interacts with CATSPERZ; the interaction is direct, Ca(2+)-dependent and connects EFCAB9 with the CatSper complex (PubMed:31056283). Dissociates from CATSPERZ at elevated pH (PubMed:31056283).|||Cytoplasm|||Mice are normal but males show severe male subfertility despite normal sperm morphology (PubMed:31056283). Subfertility is caused by defects in sperm motility: spermatozoa have a lower basal level of intracellular calcium and aberrant Ca(2+) homeostasis (PubMed:31056283).|||Only expressed after meiosis in testis.|||Testis-specific.|||flagellum http://togogenome.org/gene/10090:Or9q2 ^@ http://purl.uniprot.org/uniprot/Q8VG11 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Glp1r ^@ http://purl.uniprot.org/uniprot/O35659 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||Detected in pancreatic islets (at protein level). Detected in pancreatic islets and lungs.|||G-protein coupled receptor for glucagon-like peptide 1 (GLP-1) (PubMed:9568699). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels (By similarity). Plays a role in regulating insulin secretion in response to GLP-1 (PubMed:9568699).|||May form homodimers and heterodimers with GIPR.|||N-glycosylation enhances cell surface expression and lengthens receptor half-life by preventing degradation in the ER. http://togogenome.org/gene/10090:Or13c3 ^@ http://purl.uniprot.org/uniprot/Q8VG87 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc17a2 ^@ http://purl.uniprot.org/uniprot/Q5SZA1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions (PubMed:25972451). Mediates chloride-dependent transport of urate (PubMed:25972451). Can actively transport inorganic phosphate into cells via Na(+) cotransport (PubMed:25972451).|||Apical cell membrane|||Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.|||Expressed in the liver, kidney, placenta, lung and thyroid (at protein level). http://togogenome.org/gene/10090:Fam163b ^@ http://purl.uniprot.org/uniprot/B2RVN8|||http://purl.uniprot.org/uniprot/Q8BUM6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM163 family.|||Membrane http://togogenome.org/gene/10090:Or4c113 ^@ http://purl.uniprot.org/uniprot/L7MU54 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Uevld ^@ http://purl.uniprot.org/uniprot/Q3U1V6 ^@ Function|||Similarity|||Subunit ^@ Homodimer.|||In the C-terminal section; belongs to the LDH/MDH superfamily.|||In the N-terminal section; belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.|||Possible negative regulator of polyubiquitination. http://togogenome.org/gene/10090:Slc25a51 ^@ http://purl.uniprot.org/uniprot/Q5HZI9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Mitochondrial membrane carrier protein that mediates the import of NAD(+) into mitochondria. Mitochondrial NAD(+) is required for glycolysis and mitochondrial respiration. Compared to SLC25A52, SLC25A51-mediated transport is essential for the import of NAD(+) in mitochondria. The transport mechanism, uniport or antiport, its electrogenicity and substrate selectivity, remain to be elucidated.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Inhbb ^@ http://purl.uniprot.org/uniprot/Q04999 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Homo- or heterodimer; disulfide-linked. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B. Activin A is a homodimer of beta-A. Activin B is a homodimer of beta-B. Activin AB is a dimer of beta-A and beta-B. Interacts with FST and FSTL3 (By similarity).|||Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.|||Secreted|||Uterus, testis, ovary, lung, kidney, brain, CJ7 embryonic stem cells, and possibly in liver. http://togogenome.org/gene/10090:Or12e7 ^@ http://purl.uniprot.org/uniprot/Q7TR49 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dolk ^@ http://purl.uniprot.org/uniprot/Q8R2Y3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the polyprenol kinase family.|||Catalyzes CTP-mediated phosphorylation of dolichol, the terminal step in de novo dolichyl monophosphate (Dol-P) biosynthesis. Dol-P is a lipid carrier essential for the synthesis of N-linked and O-linked oligosaccharides and for GPI anchors.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Phospho1 ^@ http://purl.uniprot.org/uniprot/Q8R2H9 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.|||Extracellular vesicle|||Has a 120-fold higher level of expression in bone compared with a range of soft tissues.|||Mice display growth plate abnormalities, spontaneous fractures, bowed long bones, osteomalacia and scoliosis in early life (PubMed:20684022). Primary cultures of tibial growth plate chondrocytes and chondrocyte-derived matrix vesicles (MVs) show reduced mineralizing ability, and plasma samples show reduced levels of Alpl/Tnap and elevated plasma diphosphate (inorganic pyrophosphate; PPi) concentrations (PubMed:20684022). Mice lacking both Phospho1 and Alpl/Tnap show a complete absence of skeletal mineralization, leading to perinatal lethality (PubMed:20684022).|||Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho) (By similarity). Involved in the generation of inorganic phosphate for bone mineralization (PubMed:17227223). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (PubMed:26457330, PubMed:20684022). http://togogenome.org/gene/10090:Top3a ^@ http://purl.uniprot.org/uniprot/O70157|||http://purl.uniprot.org/uniprot/Q5NCT2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type IA topoisomerase family.|||Binds ssDNA. Interacts (via N-terminal region) with BLM; the interaction is direct. Directly interacts with RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM.|||Highly expressed in testis.|||Introduces a single-strand break via transesterification at a target site in duplex DNA. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand.|||Mitochondrion matrix|||Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. As an essential component of the RMI complex it is involved in chromosome separation and the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity. It is required for mtDNA decatenation and segregation after completion of replication, in a process that does not require BLM, RMI1 and RMI2. http://togogenome.org/gene/10090:Zfp935 ^@ http://purl.uniprot.org/uniprot/A0A1Y7VP04 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Rhot1 ^@ http://purl.uniprot.org/uniprot/Q8BG51 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial Rho GTPase family.|||Interacts with the kinesin-binding proteins TRAK1/OIP106 and TRAK2/GRIF1, forming a link between mitochondria and the trafficking apparatus of the microtubules (By similarity). Interacts with RAP1GDS1 (By similarity). Interacts with ARMCX1 (PubMed:28009275). Found in a complex with KIF5B, OGT, RHOT2 and TRAK1 (By similarity).|||Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution. Promotes mitochondrial fission during high calcium conditions (By similarity).|||Mitochondrion outer membrane|||Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30 (By similarity). http://togogenome.org/gene/10090:Iqcd ^@ http://purl.uniprot.org/uniprot/B2RPX1|||http://purl.uniprot.org/uniprot/Q9D3V1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DRC10 family.|||Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.|||Component of the nexin-dynein regulatory complex (N-DRC). Interacts with CFAP52 (By similarity).|||flagellum axoneme http://togogenome.org/gene/10090:Vps53 ^@ http://purl.uniprot.org/uniprot/Q8CCB4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD. Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane.|||Belongs to the VPS53 family.|||Component of the Golgi-associated retrograde protein (GARP) complex, also called VFT (VPS fifty-three) complex, composed of VPS51, VPS52, VPS53 and VPS54 (By similarity). Component of the endosome-associated retrograde protein (EARP) complex, composed of VPS51, VPS52, VPS53 and VPS50/Syndetin (By similarity). EIPR1 interacts with both EARP and GARP complexes and mediates the recruitment of the GARP complex to the trans-Golgi network (By similarity). Interacts with VPS50 in an EIPR1-independent manner (By similarity).|||Endosome membrane|||Recycling endosome|||trans-Golgi network membrane http://togogenome.org/gene/10090:Nkiras1 ^@ http://purl.uniprot.org/uniprot/Q8CEC5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation. May act by blocking phosphorylation of NFKBIB and mediating cytoplasmic retention of p65/RELA NF-kappa-B subunit. It is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB (By similarity).|||Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily.|||Cytoplasm|||In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Leu residues, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins.|||Interacts with both NF-kappa-B inhibitor alpha (NFKBIA) and beta (NFKBIB) in vitro. However, it probably only interacts with NFKBIB in vivo. Forms a complex with NFKBIB and NF-kappa-B heterodimer (p50/NFKB1 and p65/RELA). Also interacts with c-Rel (REL) (By similarity). http://togogenome.org/gene/10090:Rabl2 ^@ http://purl.uniprot.org/uniprot/E9Q9D5 ^@ Disruption Phenotype|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Exhibits phenotypes characteristic of ciliopathies. Pre-axial polydactyly. Retinal degeneration, characterized by loss of the outer nuclear layer that contains the cell body of photoreceptor cells.|||Interacts with IFT27, IFT81, IFT172, ATP6V1E1, HK1, LDHC, MAPRE1 and HSPA2.|||Isoform 2 is expressed in the testis and localizes to the mid-piece of the sperm tail (at protein level). Isoform 2 is expressed at higher levels in testis than isoform 1. Isoform 1 and isoform 2 are widely expressed and notably within other tissues containing motile cilia including the lung, trachea, brain, ovary and kidney.|||Plays an essential role in male fertility, sperm intra-flagellar transport, and tail assembly. Binds, in a GTP-regulated manner, to a specific set of effector proteins including key proteins involved in cilia development and function and delivers them into the growing sperm tail. http://togogenome.org/gene/10090:Mmel1 ^@ http://purl.uniprot.org/uniprot/E9PVK7|||http://purl.uniprot.org/uniprot/Q9JLI3 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase M13 family.|||Binds 1 zinc ion per subunit.|||Highly expressed in testis. Also expressed in ovary. Weakly or not expressed in brain, lung, heart, liver, kidney, adrenal gland and intestine.|||Inhibited by thiorphan and phosphoramidon.|||Membrane|||Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues. Shares the same substrate specificity with MME and cleaves peptides at the same amide bond.|||Mice are viable and develop normally. However, males produce smaller litters, indicating specific male fertility problems.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:Orm1 ^@ http://purl.uniprot.org/uniprot/Q60590 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Contains a beta-barrel that binds various ligands in its interior.|||Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain (By similarity). Appears to function in modulating the activity of the immune system during the acute-phase reaction.|||Secreted http://togogenome.org/gene/10090:Fbxo2 ^@ http://purl.uniprot.org/uniprot/Q80UW2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the SCF(FBXO2) complex consisting of CUL1, RBX1, SKP1 and FBXO2. Predominantly detected as heterodimer with SKP1; the heterodimer with SKP1 is not part of the SCF(FBXO2) complex.|||Cytoplasm|||Detected in brain and cochlea, in epithelial support cells and hair cells of the organ of Corti (at protein level).|||Microsome membrane|||No visible phenotype at birth. Mice are viable and fertile, but after two to four months, gradual hearing loss sets in, due to degeneration of epithelial support cells and hair cells of the organ of Corti and spiral ganglion neurodegeneration.|||Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Prevents formation of cytosolic aggregates of unfolded glycoproteins that have been retrotranslocated into the cytosol. Able to recognize and bind denatured glycoproteins, preferentially those of the high-mannose type. http://togogenome.org/gene/10090:Hmces ^@ http://purl.uniprot.org/uniprot/Q8R1M0 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SOS response-associated peptidase family.|||Chromosome|||Embryonic sublethality and altered DNA methylation, possibly caused by accumulation of 5-hydroxymethylcytosine (5hmC) in genomic DNA (PubMed:29020633). Mice do not show defects in hematopoiesis and no alterations in global 5hmC levels in bone marrow cells (PubMed:31806351). In contrast, mice display a decrease in class switch recombination (CSR) in mature activated B-cells (PubMed:31806351).|||Expressed in embryonic stem cells.|||Glu-127 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-209 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group.|||Interacts (via PIP-box motif) with PCNA.|||Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites (By similarity). Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue (By similarity). The HMCES DNA-protein cross-link is then degraded by the proteasome (By similarity). Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks (By similarity). Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (By similarity). Also involved in class switch recombination (CSR) in B-cells independently of the formation of a DNA-protein cross-link: acts by binding and protecting ssDNA overhangs to promote DNA double-strand break repair through the microhomology-mediated alternative-end-joining (Alt-EJ) pathway (PubMed:31806351). Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (PubMed:29020633).|||Was initially reported to specifically bind 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells (PubMed:23434322). It was later suggested to act as an endonuclease that specifically cleaves 5hmC-containing DNA (PubMed:29020633). However, recent studies question this activity: no alterations in global 5hmC levels are observed in bone marrow cells from knockout mice (PubMed:31806351). http://togogenome.org/gene/10090:Serpine1 ^@ http://purl.uniprot.org/uniprot/G5E899 ^@ Similarity ^@ Belongs to the serpin family. http://togogenome.org/gene/10090:Banp ^@ http://purl.uniprot.org/uniprot/Q8VBU8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BANP/SMAR1 family.|||Controls V(D)J recombination during T-cell development by repressing T-cell receptor (TCR) beta enhancer function. Binds to scaffold/matrix attachment region beta (S/MARbeta), an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Represses cyclin D1 transcription by recruiting HDAC1 to its promoter, thereby diminishing H3K9ac, H3S10ph and H4K8ac levels. Promotes TP53 activation, which causes cell cycle arrest and inhibits tumor growth (PubMed:12494467).|||Highly expressed in heart, spleen, and thymus. Isoform 1 is highly expressed in kidney, brain and testis. Isoform 3 is highly expressed in kidney and lung.|||Interaction with TP35 was reported to promotes TP53 'Ser-15' phosphorylation and nuclear accumulation causing cell cycle arrest and inhibition of tumor growth (PubMed:15701641). However, the publication has been retracted due to image duplication and manipulation. Interaction with TP35 has been confirmed by other studies (PubMed:12494467). The nuclear locatization has been confirmed by other studies (PubMed:10940556, PubMed:12494467, PubMed:15371550, PubMed:16166625).|||Interacts with TP53 (PubMed:12494467). Interacts with CUX1/CDP (PubMed:15371550). Interacts with HDAC1 (PubMed:16166625). Part of a corepressor complex containing BANP, HDAC1, SIN3A, SIN3B, RBL1 and RBL2 (PubMed:16166625).|||Nucleus http://togogenome.org/gene/10090:Stat2 ^@ http://purl.uniprot.org/uniprot/Q9QXJ2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the transcription factor STAT family.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Pacs1 ^@ http://purl.uniprot.org/uniprot/Q8K212 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with AP-1 and AP-3 but not with AP-2 complexes (By similarity). Interacts with FURIN (PubMed:9695949). Forms a ternary complex with FURIN and AP-1 (By similarity). Interacts with PKD2 (via acidic region) (PubMed:15692563). Interacts with SORL1 (By similarity). Interacts with WDR37 (PubMed:33630350).|||Belongs to the PACS family.|||Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin-coated membrane pits (By similarity). Required for normal ER Ca2+ handling in lymphocytes. Together with WDR37, it plays an essential role in lymphocyte development, quiescence and survival. Required for stabilizing peripheral lymphocyte populations (PubMed:33630350).|||Mice lacking PACS1 have reduced numbers of B-cell progenitors in the bone marrow starting at the pre-B cell stage, normal numbers of developing T-cell subpopulations in the thymus, and a reduction in splenic follicular B cells. ER Ca2+ efflux in PACS1-deficient lymphocytes is defective after antigen receptor stimulation, while ER stress and sensitivity to oxidative stress are increased. B cells have reduced IP3R expression, and show spontaneous loss of quiescence evidenced by increased proliferation and apoptosis in lymphocyte-replete environments in vivo.|||trans-Golgi network http://togogenome.org/gene/10090:Bcs1l ^@ http://purl.uniprot.org/uniprot/Q9CZP5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AAA ATPase family. BCS1 subfamily.|||Chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex (By similarity).|||Interacts with LETM1.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:B3galnt1 ^@ http://purl.uniprot.org/uniprot/Q920V1 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 31 family.|||Detected in brain, ovary, kidney, uterus and stomach (PubMed:9417047, PubMed:11463849). In ovary, specifically expressed in follicular granulosa cells and shows particularly strong expression at later stages of follicle development (PubMed:11463849).|||Detected in embryos from 12.5 days post coitum (dpc) onwards. Expressed in all four ventricles of the developing brain, with highest expression in the outer ventricular layer. Also found in the limb buds at 12.5 dpc. Detected in the brain (hippocampus) and retina at postnatal day 1. Expression in the retina is localized to the ganglion cell layer. At postnatal day 10, expression remains strong in the hippocampus where it localizes to the four CA fields and the dentate gyrus.|||Embryonic lethal. Lethality occurs at the preimplantation stage, between 3.5 and 4.5 days post-coitum (dpc).|||Golgi apparatus membrane|||Transfers N-acetylgalactosamine onto globotriaosylceramide (PubMed:9417047). Plays a critical role in preimplantation stage embryonic development (PubMed:11463849). http://togogenome.org/gene/10090:AA467197 ^@ http://purl.uniprot.org/uniprot/Q810Q5 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the complex I NDUFA4 subunit family.|||First detected at 8 dpc in the ossification center and the spinal cord. From this stage up to birth, expression extends throughout the bone tissue and strong expression is detected in the vertebrae. At 16 dpc, detected in the developing brain, including the prosencephalon, mesencephalon, diencephalon, telencephalon and rhombencephalon, and in the intestine. Faint expression at 16 dpc in the lung.|||Nucleus|||Strongly expressed in vertebrae, brain, intestine and stomach. http://togogenome.org/gene/10090:Usp34 ^@ http://purl.uniprot.org/uniprot/Q6ZQ93 ^@ Function|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the peptidase C19 family.|||Contaminating sequence. Potential poly-A sequence.|||Interacts with AXIN1 and AXIN2.|||Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. http://togogenome.org/gene/10090:Ptx4 ^@ http://purl.uniprot.org/uniprot/A0A3B2WCG1|||http://purl.uniprot.org/uniprot/E9QNW3 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Adrb1 ^@ http://purl.uniprot.org/uniprot/P34971 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB1 sub-subfamily.|||Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling (By similarity). Involved in the regulation of sleep/wake behaviors (PubMed:31473062).|||Cell membrane|||Early endosome|||Homologous desensitization of the receptor is mediated by its phosphorylation by beta-adrenergic receptor kinase.|||In brain, expressed by glutamatergic and GABAergic neurons of the dorsal pons (at protein level).|||Interacts (via C-terminus PDZ motif) with RAPGEF2; the interaction is direct. Interacts with GOPC, MAGI3 and DLG4 (By similarity).|||The PDZ domain-binding motif mediates competitive interactions with GOPC, MAGI3 and DLG4 and plays a role in subcellular location of the receptor. http://togogenome.org/gene/10090:Atp6v0e2 ^@ http://purl.uniprot.org/uniprot/A0A0N4SVQ2|||http://purl.uniprot.org/uniprot/Q91XE7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the V-ATPase e1/e2 subunit family.|||Membrane|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR.|||clathrin-coated vesicle membrane|||synaptic vesicle membrane http://togogenome.org/gene/10090:Krt28 ^@ http://purl.uniprot.org/uniprot/A6BLY7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Essential for the proper assembly of types I and II keratin protein complexes and the formation of keratin intermediate filaments in the inner root sheath (irs).|||Heterotetramer of two type I and two type II keratins.|||In the hair follicle and bulb, uniformly expressed in all three layers of the inner root sheath (the Henle layer, the Huxley layer and the cuticle) and observed in matrix cells (at protein level).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Chia1 ^@ http://purl.uniprot.org/uniprot/Q91XA9 ^@ Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.|||Cytoplasm|||Cytoplasmic granule|||Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding. Presence in saliva and gastric juice suggests a function as a digestive enzyme.|||Detected in macrophages and lung epithelial cells. Detected in the acinar cells of parotid gland and von Ebner's gland but not in submandibular and sublingual glands. Detected in gastric chief cells. Also present in parotid glandular saliva and gastric juice (at protein level). Highly expressed in submandibular gland (PubMed:11085997) and stomach. Highly expressed in parotid gland but not in submandibular and sublingual glands (PubMed:12133911). In tongue, expressed only in von Ebner's gland. Expressed at lower levels in lung.|||In parotid gland, weak expression detected at postnatal day P12, with levels increasing towards P16. In stomach, first detected at P16, with expression reaching adult levels during P20-24.|||Interacts with EGFR.|||Secreted|||Up-regulated upon pulmonary inflammation elicited by sensitization and aerosol challenge with the aeroallergen ovalbumin. Up-regulated during T-helper cell type 2 (Th2) inflammation. Induction is mediated by IL-13. http://togogenome.org/gene/10090:Ccdc134 ^@ http://purl.uniprot.org/uniprot/Q8C7V8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC134 family.|||Cytoplasm|||Endoplasmic reticulum|||In extracellular secreted form, promotes proliferation and activation of CD8(+) T cells, suggesting a cytokine-like function. Enhances cytotoxic anti-tumor activity of CD8(+) T cells. May inhibit ERK and JNK signaling activity. May suppress cell migration and invasion activity, via its effects on ERK and JNK signaling. Has a critical role in the regulation of osteogenesis and bone development.|||In the nucleus, enhances stability of the PCAF histone acetyltransferase (HAT) complex member TADA2A and thus promotes PCAF-mediated H3K14 and H4K8 HAT activity. May inhibit TADA2A-mediated TP53/p53 'Lys-321' acetylation, leading to reduced TP53 stability and transcriptional activity. May also promote TADA2A-mediated XRCC6 acetylation thus facilitating cell apoptosis in response to DNA damage.|||Interacts with TADA2A. Associates with the PCAF complex via TADA2A binding.|||Nucleus|||O-glycosylated, with additional sialic acid modifications.|||Secreted http://togogenome.org/gene/10090:Tmem145 ^@ http://purl.uniprot.org/uniprot/A0A5F8MPQ2|||http://purl.uniprot.org/uniprot/E9PUE6|||http://purl.uniprot.org/uniprot/Q8C4U2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Slco5a1 ^@ http://purl.uniprot.org/uniprot/E9PVD9|||http://purl.uniprot.org/uniprot/Q8BY69 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Lgalsl ^@ http://purl.uniprot.org/uniprot/Q8VED9 ^@ Caution|||Function|||Subunit ^@ Does not bind lactose, and may not bind carbohydrates.|||Monomer.|||Most of the residues in the galectin domain that have been shown to be critical for carbohydrate-binding in other galectins are not conserved. http://togogenome.org/gene/10090:Hgf ^@ http://purl.uniprot.org/uniprot/Q08048|||http://purl.uniprot.org/uniprot/Q8C9G5 ^@ Caution|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the peptidase S1 family. Plasminogen subfamily.|||Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts with SRPX2; the interaction increases HGF mitogenic activity.|||Has lost two of the three essential catalytic residues and so probably has no enzymatic activity.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types (PubMed:20624990). Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization (By similarity). Activates MAPK signaling following TMPRSS13 cleavage and activation (By similarity).|||Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.|||The single-chain precursor undergoes proteolytic processing by TMPRSS13 resulting in an active two-chain form. http://togogenome.org/gene/10090:Ldhal6b ^@ http://purl.uniprot.org/uniprot/Q8BVP2 ^@ Similarity ^@ Belongs to the LDH/MDH superfamily. LDH family. http://togogenome.org/gene/10090:E2f4 ^@ http://purl.uniprot.org/uniprot/Q8R0K9 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the E2F/DP family.|||Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with TFDP1/Dp-1 to E2F sites. The E2F4/TFDP1 dimer interacts preferentially with pocket protein RBL1, which inhibits the E2F transactivation domain. Lower affinity interaction has been found with retinoblastoma protein RB1. Interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation. Interacts with HCFC1. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with PML. Interacts with CEBPA (when phosphorylated) (By similarity).|||Differentially phosphorylated in vivo.|||Nucleus|||Postnatal lethality, probably due to the absence of ciliated cells from the entire airway epithelium and the epithelium of the submucosal glands in the paranasal sinuses. In the nasal epithelium, ciliated cells are replaced by columnar secretory cells that produce mucin-like substances. In the proximal lung, reduction in club cells is also observed. The combination of no ciliated cells and excess mucous cells leads for the chronic rhinitis and increased susceptibility to opportunistic infections that cause lethality.|||Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F4 binds with high affinity to RBL1 and RBL2. In some instances can also bind RB1. Specifically required for multiciliate cell differentiation: together with MCIDAS and E2F5, binds and activate genes required for centriole biogenesis. http://togogenome.org/gene/10090:Cdcp1 ^@ http://purl.uniprot.org/uniprot/Q5U462 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ A soluble form may also be produced by proteolytic cleavage at the cell surface (shedding). Another peptide of 80 kDa (p80) is present in cultured keratinocytes probably due to tryptic cleavage at an unidentified site on the N-terminal side. Converted to p80 by plasmin, a trypsin-like protease (By similarity).|||Cell membrane|||Interacts with CDH2/N-cadherin, CDH3/P-cadherin, SDC1/syndecan-1, SDC4/syndecan-4 and the serine protease ST14/MT-SP1. Also interacts SRC and PRKCG/protein kinase C gamma (By similarity).|||May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a novel marker for leukemia diagnosis and for immature hematopoietic stem cell subsets. Belongs to the tetraspanin web involved in tumor progression and metastasis.|||N-glycosylated.|||Phosphorylated on tyrosine by kinases of the SRC family such as SRC and YES as well as by the protein kinase C gamma/PRKCG. Dephosphorylated by phosphotyrosine phosphatases. Also phosphorylated by suramin, a heparin analog. Tyrosine phosphorylated in response to dissociation of integrin alpha-6 beta-4 from laminin-5 (By similarity). http://togogenome.org/gene/10090:Nrsn2 ^@ http://purl.uniprot.org/uniprot/Q5HZK2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the VMP family.|||Expressed specifically in brain where it is widely expressed, with highest levels of expression in thalamus and hypothalamus. In brain, found in neural cell bodies and detected in many regions of the limbic system, such as the septum nucleus, horizontal and vertical limbs of the diagonal band, hippocampus, amygdaloid nucleus, and habernula nucleus. Also localizes to small vesicles found in the perinuclear region of Neuro2a and PC12 cells.|||In cerebral cortex first detected at 15.5 dpc with increasing levels of expression observed during postnatal stages.|||May play a role in maintenance and/or transport of vesicles.|||Membrane http://togogenome.org/gene/10090:Nhlrc2 ^@ http://purl.uniprot.org/uniprot/Q8BZW8 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Full embryonic lethality. No homozygous embryos are present at 2.5 dpc.|||Monomer.|||Required for normal embryonic development.|||Ubiquitous.|||cytosol http://togogenome.org/gene/10090:Bex4 ^@ http://purl.uniprot.org/uniprot/Q14BB8|||http://purl.uniprot.org/uniprot/Q9CWT2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the BEX family.|||Cytoplasm|||Expressed in both Sertoli and germ cells as well as interstitial area of the testis (at protein level).|||Interacts with alpha-tubulin. Interacts with SIRT2.|||May play a role in microtubule deacetylation by negatively regulating the SIRT2 deacetylase activity toward alpha-tubulin and thereby participate in the control of cell cycle progression and genomic stability (By similarity). In absence of reductive stress, acts as a pseudosubstrate for the CRL2(FEM1B) complex: associates with FEM1B via zinc, thereby preventing association between FEM1B and its substrates (PubMed:34562363).|||Nucleus|||Ubiquitinated and degraded by the proteasome.|||Up-regulated by cadmium in testis (at protein level) (PubMed:28295929). Up-regulated by curcumin (PubMed:28145533).|||spindle pole http://togogenome.org/gene/10090:Taf5 ^@ http://purl.uniprot.org/uniprot/F8VPY2|||http://purl.uniprot.org/uniprot/Q8C092 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat TAF5 family.|||Distinct domains of TAF5/TAFII100 are required for functional interaction with transcription factor TFIIFB (RAP30) and incorporation into the TFIID complex.|||Homodimer. Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TAF5 forms the TFIID-A module together with TAF3 and TBP, and in TFIID-B with TAF8. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TADA3L, SUPT3H/SPT3, TAF2, TAF4, TAF5, GCN5L2/GCN5, TAF10 and TRRAP. TBP is not part of the TFTC-HAT complex. Interacts strongly with the histone H4-related TAF6 and the histone H3-related TAF9, as well as a stable complex comprised of both TAF6 and TAF9. Apparently weaker interactions with TBP, TAF1, TAF11, and TAF12, but not TAF7, also have been observed.|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TAF5 is involved in two modules of TFIID, in TFIID-A together with TAF3 and TBP, and in TFIID-B with TAF8. Involved in contacts between TFIID and TFIIF in the PIC. http://togogenome.org/gene/10090:Vmn1r253 ^@ http://purl.uniprot.org/uniprot/K9J7G6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plac1 ^@ http://purl.uniprot.org/uniprot/Q9JI83 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the PLAC1 family.|||Expressed in placenta.|||May play a role in placental development.|||Secreted|||Strongly expressed at 7 dpc and gradually declines with the progression of embryogenesis. Expression detected from 7.5 to 14.5 dpc in ectoplacental cone, trophoblast giant cells, and labyrinthine trophoblasts. http://togogenome.org/gene/10090:Mrpl57 ^@ http://purl.uniprot.org/uniprot/Q9CQF8 ^@ Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the mitochondrion-specific ribosomal protein mL63 family.|||Identified only in the intact 55S subunit. It is unknown whether it belongs to the 28S or to the 39S subunit. May localize at the subunit interface and dissociate from the 55S mitoribosome during subunit separation.|||Mitochondrion http://togogenome.org/gene/10090:Spata13 ^@ http://purl.uniprot.org/uniprot/Q5DU57 ^@ Activity Regulation|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Regulates cell migration and adhesion assembly and disassembly through a RAC1, PI3K, RHOA and AKT1-dependent mechanism. Increases both RAC1 and CDC42 activity, but decreases the amount of active RHOA (By similarity). Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.|||Both the ABR and the SH3 domains contribute to maintaining the protein in an inhibited conformation by associating with the C-terminal tail. Binding of these domains to the C-terminal tail inhibits the activity of the protein by blocking a region that is required for its GEF activity (By similarity).|||Cytoplasm|||Expression is aberrantly enhanced in most colorectal tumors.|||Interacts (via ABR and SH3 domain) with APC. The binding of APC enhances its GEF activity by relieving it from an autoinhibitory conformation, in which the ABR and SH3 domains are associated with the C-terminal tail. Interacts (via C-terminal tail) with PPP1R9B (via C-terminus). Interacts with RAC1 (By similarity).|||The C-terminal tail is required for its GEF activity.|||filopodium|||lamellipodium|||ruffle membrane http://togogenome.org/gene/10090:Rps6ka1 ^@ http://purl.uniprot.org/uniprot/E9PWV3|||http://purl.uniprot.org/uniprot/P18653|||http://purl.uniprot.org/uniprot/Q505N6|||http://purl.uniprot.org/uniprot/Q810V8 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by phosphorylation at Ser-221 by PDPK1. Autophosphorylated on Ser-369, as part of the activation process. May be phosphorylated at Thr-348 and Ser-352 by MAPK1/ERK2 and MAPK3/ERK1 (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Cytoplasm|||Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation. Interacts with ETV1/ER81 and FGFR1 (By similarity).|||Intestine, thymus, and lung.|||N-terminal myristoylation results in an activated kinase in the absence of added growth factors.|||Nucleus|||Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (By similarity). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (By similarity). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (By similarity). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (By similarity). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (By similarity). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (By similarity). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (By similarity). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (By similarity). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (By similarity). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:10635333). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (By similarity). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (By similarity). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (By similarity).|||Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-562 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-369, allowing binding of PDPK1, which in turn phosphorylates Ser-221 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD (By similarity). http://togogenome.org/gene/10090:Rnf125 ^@ http://purl.uniprot.org/uniprot/Q9D9R0 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated, leading to its subsequent proteasomal degradation.|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as RIGI, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53. Acts as a negative regulator of type I interferon production by mediating ubiquitination of RIGI at 'Lys-181', leading to RIGI degradation. Mediates ubiquitination and subsequent degradation of p53/TP53. Mediates ubiquitination and subsequent degradation of JAK1. Acts as a positive regulator of T-cell activation.|||Golgi apparatus membrane|||Interacts with UBE2D1. Interacts with VCP/p97; leading to recruit RNF125 to RIGI and promote ubiquitination of RIGI.|||The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin). http://togogenome.org/gene/10090:Rtl3 ^@ http://purl.uniprot.org/uniprot/Q6P1Y1 ^@ Developmental Stage|||Function|||Miscellaneous|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in embryonic myogenic progenitor cells, not expressed in adult and aged satellite cells.|||In myogenic progenitor cells, not expressed during early myogenic development, appears during early formation of the satellite cell pool (from 12.5 dpc to 17.5 dpc), before being completely down-regulated during adquisition of satellite cell quiescence.|||May function as a transcriptional regulator (Probable). Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal (PubMed:27446912).|||Nucleus|||RTL3 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes. http://togogenome.org/gene/10090:Wtap ^@ http://purl.uniprot.org/uniprot/E0CYH0|||http://purl.uniprot.org/uniprot/Q9ER69 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29535189, PubMed:29547716). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (PubMed:29547716). Required for accumulation of METTL3 and METTL14 to nuclear speckle (By similarity). Acts as a mRNA splicing regulator (By similarity). Regulates G2/M cell-cycle transition by binding to the 3' UTR of CCNA2, which enhances its stability (By similarity). Impairs WT1 DNA-binding ability and inhibits expression of WT1 target genes (By similarity).|||Belongs to the fl(2)d family.|||Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM (PubMed:29535189, PubMed:29547716). The MAC subcomplex is composed of METTL3 and METTL14 (PubMed:29535189, PubMed:29547716). The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B) (PubMed:29535189, PubMed:29547716). Interacts with WT1 (By similarity). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3 (By similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145).|||Cytoplasm|||Death at E6.5 due to defects in cell proliferation.|||Nucleus speckle|||nucleoplasm http://togogenome.org/gene/10090:1700093K21Rik ^@ http://purl.uniprot.org/uniprot/Q810S2 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Sf3b6 ^@ http://purl.uniprot.org/uniprot/P59708 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42. Within the SF3B complex interacts directly with SF3B1. The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2. Component of the minor spliceosome, which splices U12-type introns.|||Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex. SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Directly contacts the pre-mRNA branch site adenosine for the first catalytic step of splicing. Enters the spliceosome and associates with the pre-mRNA branch site as part of the 17S U2 or, in the case of the minor spliceosome, as part of the 18S U11/U12 snRNP complex, and thus may facilitate the interaction of these snRNP with the branch sites of U2 and U12 respectively.|||Nucleus http://togogenome.org/gene/10090:Gm3183 ^@ http://purl.uniprot.org/uniprot/D3YUJ6 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Atmin ^@ http://purl.uniprot.org/uniprot/Q6P9S1 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Interacts via its C-terminus with ATM. Interacts with DYNLL; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. ATMIN.|||Nucleus|||Transcription factor. Plays a crucial role in cell survival and RAD51 foci formation in response to methylating DNA damage. Involved in regulating the activity of ATM in the absence of DNA damage. May play a role in stabilizing ATM (By similarity). Binds to the DYNLL1 promoter and activates its transcription. http://togogenome.org/gene/10090:Gabrq ^@ http://purl.uniprot.org/uniprot/B1AUQ5|||http://purl.uniprot.org/uniprot/Q0VEX8|||http://purl.uniprot.org/uniprot/Q9JLF1 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRQ sub-subfamily.|||Cell membrane|||GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.|||Generally pentameric. This subunit coassembles with alpha-2, beta-1 and gamma-1.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Cox7b ^@ http://purl.uniprot.org/uniprot/P56393|||http://purl.uniprot.org/uniprot/Q5FW98 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cytochrome c oxidase VIIb family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix (By similarity). Plays a role in proper central nervous system (CNS) development in vertebrates (By similarity).|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Myo9b ^@ http://purl.uniprot.org/uniprot/E9PWZ6|||http://purl.uniprot.org/uniprot/E9PZW8|||http://purl.uniprot.org/uniprot/Q3TRQ0 ^@ Caution|||Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Mfhas1 ^@ http://purl.uniprot.org/uniprot/Q3V1N1 ^@ Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with RAF1. Interacts with HSPD1. Interacts with PPP2CA; retains PPP2CA into the cytoplasm and excludes it from the nucleus. Interacts with PPP2R2A; the interaction is direct. Interacts with PJA2.|||Probable GTP-binding protein (By similarity). Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways (PubMed:20616063, PubMed:26599367). Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP-1 subunit JUN which is required for proper activation of the transcription factor (By similarity). Both inhibits and activates the TLR2-dependent signaling pathway (PubMed:26599367). Positively regulates the TLR2 signaling pathway to activate specifically the downstream p38 and JNK MAP kinases and promote the polarization of macrophages toward the pro-inflammatory M1 phenotype. It may also play a role in the regulation of inflammation induced by high glucose through the PKB/AKT signaling pathway. Also involved in erythrocyte differentiation through activation of the ERK1/ERK2 signaling pathway (By similarity).|||Ubiquitinated. Ubiquitination by PJA2 does not lead MFHAS1 to proteasomal degradation but positively regulates its function in polarization of macrophages.|||Up-regulated by lipopolysaccharides (LPS) (at protein level). http://togogenome.org/gene/10090:R3hdm2 ^@ http://purl.uniprot.org/uniprot/Q80TM6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Acot9 ^@ http://purl.uniprot.org/uniprot/Q9R0X4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Active on long chain acyl-CoAs.|||Belongs to the acyl coenzyme A hydrolase family.|||Interacts with NYAP1, NYAP2 and MYO16.|||Mitochondrion http://togogenome.org/gene/10090:Tc2n ^@ http://purl.uniprot.org/uniprot/Q91XT6 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Kif9 ^@ http://purl.uniprot.org/uniprot/Q3V3Y6|||http://purl.uniprot.org/uniprot/Q8C0X6|||http://purl.uniprot.org/uniprot/Q9WV04 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Essential for normal male fertility and for progressive motility of spermatozoa.|||Highly expressed in the testis (at protein level) (PubMed:32072696). Weakly expressed in the brain, thymus, lung and heart (PubMed:32072696).|||Interacts with HYDIN.|||Mice exhibit impaired sperm motility and male subfertility and flagella show an asymmetric waveform pattern, which leads to a circular motion of spermatozoa.|||cytoskeleton|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Ugt2a1 ^@ http://purl.uniprot.org/uniprot/Q80X89 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the UDP-glycosyltransferase family.|||Membrane|||UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile. Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds. Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterones) and estrogens (estradiol and estriol). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption. Shows a high affinity to aliphatic odorants such as citronellol as well as olfactory tissue specificity, and therefore may be involved in olfaction. http://togogenome.org/gene/10090:Cyp2s1 ^@ http://purl.uniprot.org/uniprot/Q9DBX6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ A cytochrome P450 monooxygenase involved in the metabolism of retinoids and eicosanoids. In epidermis, may contribute to the oxidative metabolism of all-trans-retinoic acid. For this activity, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Additionally, displays peroxidase and isomerase activities toward various oxygenated eicosanoids such as prostaglandin H2 (PGH2) and hydroperoxyeicosatetraenoates (HPETEs). Independently of cytochrome P450 reductase, NADPH, and O2, catalyzes the breakdown of PGH2 to hydroxyheptadecatrienoic acid (HHT) and malondialdehyde (MDA), which is known to act as a mediator of DNA damage.|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Microsome membrane http://togogenome.org/gene/10090:Gm20498 ^@ http://purl.uniprot.org/uniprot/E9PVN6|||http://purl.uniprot.org/uniprot/Q3UFD0|||http://purl.uniprot.org/uniprot/Q9D6K5 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the COX16 family.|||Binds (via the PDZ domain) to isoform 2A of SYNJ2 (via the unique motif in the C-terminus) (By similarity). Interacts (via C-terminus) with RALBP1. Interacts (via PDZ domain) with ACVR2A (via C-terminus) and ACVR2B (via C-terminus). Forms a ternary complex with ACVR2A and RALBP1 (PubMed:11882656, PubMed:16648306). Interacts with MAPK12 (By similarity). Interacts with DLL1; enhances DLL1 protein stability, and promotes notch signaling in endothelial cells (By similarity).|||Isoform 1 and isoform 2 are widely expressed, notably in brain, heart, lung, liver, kidney, skeletal muscle, ovary and testis. Isoform 3 is detected only in heart, spleen and testis.|||Isoform 1 regulates endocytosis of activin type 2 receptor kinases through the Ral/RALBP1-dependent pathway and may be involved in suppression of activin-induced signal transduction. Isoform 2 and isoform 3 show a stimulatory affect on activin-induced signal transduction and enhance activin type 2 expression at the cell surface.|||Membrane|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||Up-regulated between 12 and 24 hours after treatment with activin A and lipopolysaccharide (LPS). Down-regulated by calcium ionophore A23187.|||perinuclear region http://togogenome.org/gene/10090:Alppl2 ^@ http://purl.uniprot.org/uniprot/P24823|||http://purl.uniprot.org/uniprot/Q7TPW4 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Alkaline phosphatase that can hydrolyze various phosphate compounds.|||Belongs to the alkaline phosphatase family.|||Binds 1 Mg(2+) ion.|||Binds 2 Zn(2+) ions.|||Cell membrane|||Embryo and testis.|||Homodimer.|||In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP).|||Inhibited by L-leucine, EDTA and heat.|||Membrane|||No visible phenotype (PubMed:9056646). Mice reproduce normally, give birth to live offspring and do not display any obvious phenotypic abnormalities (PubMed:9056646). http://togogenome.org/gene/10090:Usp5 ^@ http://purl.uniprot.org/uniprot/P56399|||http://purl.uniprot.org/uniprot/Q3U4W8 ^@ Function|||Similarity|||Subunit ^@ Belongs to the peptidase C19 family.|||Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity (By similarity).|||Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.|||Interacts with TRIML1. http://togogenome.org/gene/10090:G6pd2 ^@ http://purl.uniprot.org/uniprot/G3UWD6|||http://purl.uniprot.org/uniprot/P97324 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated by ELP3; acetylation inhibits its homodimerization and enzyme activity. Deacetylated by SIRT2; deacetylation stimulates its enzyme activity (By similarity).|||Belongs to the glucose-6-phosphate dehydrogenase family.|||Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.|||Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis.|||Has NADP both as cofactor (bound to the N-terminal domain) and as structural element bound to the C-terminal domain.|||Homotetramer; dimer of dimers (PubMed:9169132). Interacts with SIRT2; the interaction is enhanced by H(2)O(2) treatment (By similarity).|||Membrane|||Testis.|||cytosol http://togogenome.org/gene/10090:Dhrs7b ^@ http://purl.uniprot.org/uniprot/I7DM66|||http://purl.uniprot.org/uniprot/Q99J47 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Endoplasmic reticulum membrane|||Putative oxidoreductase. http://togogenome.org/gene/10090:Hyls1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1K7|||http://purl.uniprot.org/uniprot/Q9CXX0 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the HYLS1 family.|||Cytoplasm|||Detected at each embryonic stage, the highest expression level observed at 11 dpc.|||Expressed in hippocampus and dentate gyrus of 3-month adult brain.|||Plays a role in ciliogenesis.|||centriole|||cilium http://togogenome.org/gene/10090:Pramel46 ^@ http://purl.uniprot.org/uniprot/A0A0J9YVD0 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Itih2 ^@ http://purl.uniprot.org/uniprot/G3X977|||http://purl.uniprot.org/uniprot/Q61703 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ITIH family.|||Expressed in both liver and brain.|||Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.|||I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (HC) and one light chain, bikunin. Inter-alpha-inhibitor (I-alpha-I) is composed of ITIH1/HC1, ITIH2/HC2 and bikunin.|||May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.|||Phosphorylated by FAM20C in the extracellular medium.|||Secreted http://togogenome.org/gene/10090:Kctd15 ^@ http://purl.uniprot.org/uniprot/Q8K0E1 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ During embryonic development, interferes with neural crest formation. Inhibits AP2 transcriptional activity by interaction with its activation domain (By similarity).|||Interacts with TFAP2A; this interaction inhibits TFAP2A transcriptional activation.|||Localizes to neurons in areas of the cerebral cortex, cerebellum and hypothalamus (at protein level).|||Nucleus http://togogenome.org/gene/10090:Gipc2 ^@ http://purl.uniprot.org/uniprot/Q9Z2H7 ^@ Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GIPC family.|||Cytoplasm|||Expressed in kidney and lung (at protein level).|||Probably interacts with SEMA5A. http://togogenome.org/gene/10090:Ndp ^@ http://purl.uniprot.org/uniprot/P48744 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates the canonical Wnt signaling pathway through FZD4 and LRP5 coreceptor. Plays a central role in retinal vascularization by acting as a ligand for FZD4 that signals via stabilizing beta-catenin (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts in concert with TSPAN12 to activate FZD4 independently of the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1). May be involved in a pathway that regulates neural cell differentiation and proliferation. Possible role in neuroectodermal cell-cell interaction.|||Expressed in the outer nuclear, inner nuclear and ganglion cell layers of the retina.|||Homodimer; disulfide-linked (By similarity). Component of a complex, at least composed of TSPAN12, FZD4, LRP5/6 and norrin (NDP). Binds FZD4 with high affinity. Interacts with LRP6 (via Beta-propellers 1 and 2).|||Secreted http://togogenome.org/gene/10090:Nap1l3 ^@ http://purl.uniprot.org/uniprot/Q794H2 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the nucleosome assembly protein (NAP) family.|||Cytoplasm|||Expressed in brain.|||Nucleus http://togogenome.org/gene/10090:Ppp2r2c ^@ http://purl.uniprot.org/uniprot/Q8BG02 ^@ Function|||Similarity|||Subunit ^@ Belongs to the phosphatase 2A regulatory subunit B family.|||PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with IER5 (By similarity).|||The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. http://togogenome.org/gene/10090:Sowahb ^@ http://purl.uniprot.org/uniprot/Q8BZW2 ^@ Similarity ^@ Belongs to the SOWAH family. http://togogenome.org/gene/10090:Or2b11 ^@ http://purl.uniprot.org/uniprot/Q7TS30 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnrc6a ^@ http://purl.uniprot.org/uniprot/Q3UHK8 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GW182 family.|||Detected in the yolk sac endoderm at embryonic stage 9.5 dpc.|||Development up until embryonic stage 9.5 dpc is normal. After this point, mortality rates increase rapidly with less than 5% survival at stage 12.5 dpc. The yolk sac endoderm is abnormally thin with fewer mitotic cells. In addition there are fewer blood islands in the yolk sac, associated with impaired hematopoiesis. Expression of many miRNA-regulated genes in the yolk sac is abnormal, and in particular there is marked derepression of genes involved in regulation of apoptosis and the cell cycle. miRNA biogenesis is not affected.|||Interacts with AGO2. Interacts with AGO1, AGO3 and AGO4. Interacts with CNOT1; the interaction is direct and mediates the association with the CCR4-NOT complex. Interacts with ZC3H12A. Interacts with SND1. Interacts with GARRE1 (By similarity).|||P-body|||Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:22187428). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:22187428). As a scaffolding protein, associates with argonaute proteins bound to partially complementary mRNAs, and can simultaneously recruit CCR4-NOT and PAN deadenylase complexes (By similarity). http://togogenome.org/gene/10090:Odf1 ^@ http://purl.uniprot.org/uniprot/A6H656 ^@ Function ^@ Component of the outer dense fibers (ODF) of spermatozoa. ODF are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. http://togogenome.org/gene/10090:Sp7 ^@ http://purl.uniprot.org/uniprot/Q8VI67 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Sp1 C2H2-type zinc-finger protein family.|||Death in the immediate postnatal period due to difficulty in breathing. Mice rapidly become cyanotic and die within 15 min of birth. New-born homozygous show severe inward bending of forelimbs and hindlimbs. They develop a normal cartilage skeleton but fail to form bone and to express osteoblast-specific marker genes. In endochondral skeletal elements, mesenchymal cells together with osteoclasts and blood vessels, invade the mineralized cartilage matrix.|||In response to ascorbic acid induction, expression is activated by NFE2L1 in osteoblasts.|||Interacts with RIOX1; the interaction is direct and inhibits transcription activator activity.|||Nucleus|||Osteoblast/chondrocyte specific.|||Propionylated (PubMed:30026585). Depropionylation at Lys-368 by SIRT7 activates transcription factor activity and positively regulates bone formation by osteoblasts (PubMed:30026585).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Transcriptional activator essential for osteoblast differentiation (PubMed:11792318, PubMed:17510056, PubMed:30026585). Binds to SP1 and EKLF consensus sequences and to other G/C-rich sequences (PubMed:11792318, PubMed:17510056).|||Ubiquitination at leads to proteasomal degradation. SP7 is a short-live protein with an endogenous half-life of approximately 12 hours (By similarity). http://togogenome.org/gene/10090:Or1ad6 ^@ http://purl.uniprot.org/uniprot/Q8VGH0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdha12 ^@ http://purl.uniprot.org/uniprot/Q91Y18 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Ferd3l ^@ http://purl.uniprot.org/uniprot/Q923Z4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Detected in the developing central nervous system, in particular in embryonic ventral neural tube, brain, and spinal cord. Detected in embryonic intestine. Detected in embryonic and adult thalamus, hypothalamus, midbrain, pons and medulla.|||Heterodimer with TCF3/E12. Interacts with the bHLH domain of TCF3/E12.|||Nucleus|||Transcription factor that binds to the E-box and functions as inhibitor of transcription. DNA binding requires dimerization with an E protein. Inhibits transcription activation by ASCL1/MASH1 by sequestering E proteins. http://togogenome.org/gene/10090:Hoxa13 ^@ http://purl.uniprot.org/uniprot/Q62424 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Abd-B homeobox family.|||Binds DNA as a homodimer. Interacts with MEIS1, MEIS2 and MEIS3.|||Defects in Hoxa13 are the cause of hypodactyly (Hd), a condition characterized by profound deficiency of digital arch structures.|||Nucleus|||Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Or5k8 ^@ http://purl.uniprot.org/uniprot/A0A140T8K4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gstt3 ^@ http://purl.uniprot.org/uniprot/Q99L20 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Theta family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Shows high activity towards 4-nitrobenzyl chloride (4-NBC). Also has lower activity towards 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP), cumene hydroperoxide, 1-chloro-2,4-dinitrobenzene (CDNB), 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl), and ethacrynic acid.|||Cytoplasm|||Expressed strongly in liver, and at lower levels in kidney and testis.|||Homodimer. http://togogenome.org/gene/10090:Fgd4 ^@ http://purl.uniprot.org/uniprot/Q91ZT5 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Activates MAPK8 (By similarity). Plays a role in regulating the actin cytoskeleton and cell shape. Promotes the formation of lamellipodia.|||Detected in thymus, lung, heart, skeletal muscle, small intestine, liver, kidney, spleen and testis. Expressed in all parts of the brain and in the spinal cord at embryonic, postnatal, and adult stages. Levels of expression are lower in postnatal and adult tissues than in embryonic tissues.|||Homooligomer.|||The part of the protein spanning the actin filament-binding domain together with the DH domain and the first PH domain is necessary and sufficient for microspike formation. Activation of MAPK8 requires the presence of all domains with the exception of the actin filament-binding domain (By similarity).|||cytoskeleton|||filopodium http://togogenome.org/gene/10090:Tbc1d20 ^@ http://purl.uniprot.org/uniprot/Q9D9I4 ^@ Disease Annotation|||Domain|||Function|||Subcellular Location Annotation ^@ Defects in Tbc1d20 are the cause of spontaneous autosomal recessive blind sterile (bs) phenotype. Bs animals exhibit embryonic non-progressive nuclear cataracts and spermatid abnormalities associated with male infertility.|||GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude (By similarity). Involved in maintaining endoplasmic reticulum structure (By similarity).|||Membrane|||The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site. http://togogenome.org/gene/10090:Atoh7 ^@ http://purl.uniprot.org/uniprot/Q9Z2E5 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in retinal ganglion cells (PubMed:26392540). Expressed in the cerebellum, trapezoid body, ventral nucleus of the lateral lamniscus and in areas of the auditory hindbrain such as the cochlear nucleus, lateral superior olive and medial nucleus of the trapezoid body (PubMed:17977745). Expressed in the modiolar nerve root and in the cochlear in a small group of bushy neurons within the acoustic nerve (PubMed:17977745). Expressed weakly in the sensory epithelia of the saccule and utricle (PubMed:17977745).|||Expression initiates at 11 dpc in the central optic cup and is detected in retinal progenitor cells until birth (PubMed:9806930). In addition to the eye, only expressed in the developing tenth cranial ganglion between 13.5 dpc and 15.5 dpc (PubMed:9806930). Expressed in the retina and faintly expressed in the caudal rhombic lip and rostral rhombic lip at 12.5 dpc (PubMed:17977745). Expressed in the presumptive ventral cochlear nucleus and in initial axons emerging from the cochlear nucleus and extending via the trapezoid body towards the ipsilateral lateral superior olive at 14.5 dpc (PubMed:17977745). Expressed in the cochlear duct epithelium between 14.5 dpc and 17.5 dpc (PubMed:17977745). Expressed in the retina at 16.5 dpc (PubMed:17977745). Expressed in the cochlear nucleus at 16.5 dpc and P8 (PubMed:17977745). Abundantly expressed in the ventral cochlear nucleus and axons originating from these cells that form branches in the lateral superior olive at 18.5dpc (PubMed:17977745).|||Forms a heterodimer with TCF3 isoform E47; interaction may be required for DNA-binding in certain situations.|||Mice are viable and fertile but display multiple optic abnormalities resulting in blindness (PubMed:11493566, PubMed:11156601, PubMed:12451142, PubMed:26392540, PubMed:33712461). Normal hindbrain morphology, however mice show disruption of brainstem auditory signaling and binaural processing (PubMed:17977745). Loss of retinal circadian rhythm photoentrainment, and decreased expression of Opn5 (PubMed:12451142, PubMed:26392540). Loss of the retinohypothalamic tract connecting the retina to the suprachiasmatic nuclei (PubMed:12451142). Loss of axon bundles, optic nerves and chiasmata, with a decreased thickness of the retinal inner plexiform layer and inner nuclear layer (PubMed:11493566). Increase in cone photoreceptors and decrease in dopaminergic amacrine cells in the ganglion cell layer (PubMed:11493566, PubMed:33712461). Loss of retinal Pou4f2-expressing retinal ganglion cells resulting in a decrease in the thickness of the retinal cell layer and loss of the nerve fiber layer (PubMed:11493566, PubMed:11156601). Significant reduction in RGCs and compensatory increase in cone photoreceptors and neurogenic progenitor cells at 14.5 dpc (PubMed:33712461). The 1% of RGCs that survive into adulthood show severe axon guidance defects and extend into the retina instead of targeting the optic disk with only a few forming a rudimentary optic nerve (PubMed:33712461). No observable RGC axonal terminals in the brain and persistent retinal hyaloid vasculature into adulthood (PubMed:33712461). In Atoh7 and Bax double knockout mice, significant reduction in RGCs and compensatory increase in cone photoreceptor cells and neurogenic retinal progenitor cells at 14.5 dpc, however there is no difference in the number of RGCs derived from Atoh7-expressing cells and cone photoreceptors during adulthood (PubMed:33712461). Reduced light spatial receptive fields, slower light-driven responses and reduced pupillary light response (PubMed:33712461).|||Nucleus|||Perikaryon|||Transcription factor that binds to DNA at the consensus sequence 5'-CAG[GC]TG-3' (PubMed:33712461). Dimerization with TCF3 isoform E47 may be required in certain situations (By similarity). Binds to gene promoters and enhancer elements, and thereby regulates a transcriptional program of retinal ganglion cell (RGC) determinant genes (PubMed:33712461). Although the exact mechanism is not certain, retinal transcription regulation by ATOH7 has a role in RGC determination and survival, photoreceptor population development, targeting of RGC axons to the optic nerve and development of the retino-hypothalamic tract (PubMed:11493566, PubMed:11156601, PubMed:12451142, PubMed:33712461). Binds to its own promoter and enhancer sequences, suggesting autoregulation of ATOH7 transcription (PubMed:33712461). Required for retinal circadian rhythm photoentrainment (PubMed:12451142, PubMed:26392540). Plays a role in brainstem auditory signaling and binaural processing (PubMed:17977745).|||axon http://togogenome.org/gene/10090:Drc3 ^@ http://purl.uniprot.org/uniprot/Q9D5E4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DRC3 family.|||Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.|||Component of the nexin-dynein regulatory complex (N-DRC). Interacts with DRC1 (By similarity). Interacts with TCTE1/DRC5 (PubMed:28630322). Interacts with DRC7 (PubMed:31961863).|||cilium|||cilium axoneme|||flagellum|||flagellum axoneme http://togogenome.org/gene/10090:Fkbp1a ^@ http://purl.uniprot.org/uniprot/P26883 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the FKBP-type PPIase family. FKBP1 subfamily.|||Inhibited by both FK506 and rapamycin.|||Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation (By similarity). Interacts with ACVR1B and SMAD7 (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). Interacts directly with RYR2 and RYR3 (By similarity). Interacts directly with RYR1 (By similarity). Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner (By similarity).|||Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity).|||Sarcoplasmic reticulum membrane|||cytosol http://togogenome.org/gene/10090:Lrrk2 ^@ http://purl.uniprot.org/uniprot/Q5S006 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated (PubMed:28720718, PubMed:29212815). Phosphorylation of Ser-910 and Ser-935 or Ser-1444 facilitates interaction with YWHAG (By similarity). Phosphorylation of Ser-910 and/or Ser-935 facilitates interaction with SFN (By similarity).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.|||Contrary to LRRK1 knockout mice, LRRK2 knockout animals do not show obvious bone phenotypes. Osteoclast precursors differentiate into functional multinucleated cells.|||Cytoplasmic vesicle|||Endoplasmic reticulum membrane|||Endosome|||Expressed in the brain (at protein level) (PubMed:28720718). Detected throughout the adult brain. Expressed in deep cerebral cortex layers, superficial cingulate cortex layers, the piriform cortex, hippocampal formation, caudate putamen, substantia nigra, the basolateral and basomedial anterior amygdala nuclei, reticular thalamic nucleus and also in the cerebellar granular cell layer. Highly expressed in the striatum, cortex and olfactory tubercle. Little or no expression in the substantia nigra, where dopaminergic neurons preferentially degenerate in Parkinson disease. Expression is particularly high in brain dopaminoceptive areas. High and strikingly specific expression in striatum and parts of cortex and no signals in dopamine neurons.|||Golgi apparatus membrane|||Homodimer (By similarity). Interacts with PRKN, PRDX3 and TPCN2 (By similarity). Interacts with VPS35 and RAB29 (PubMed:23395371). Interacts (via ROC domain) with SEC16A (PubMed:25201882). Interacts with APP; interaction promotes phosphorylation of 'Thr-743' of APP (PubMed:28720718). Interacts with MAPT (By similarity). Interacts with RAB8A, RAB10, and RAB12 (By similarity). Interacts with YWHAG; this interaction is dependent on phosphorylation of Ser-910 and either Ser-935 or Ser-1444 (By similarity). Interacts with SFN; this interaction is dependent on phosphorylation of Ser-910 and/or Ser-935 (By similarity).|||Kinase activity is regulated by the GTPase activity of the ROC domain (Probable). GTP-bound LLRK2 kinase activity is stimulated by RAB29 (Probable). Inhibited by small molecule inhibitors MLi-2 and LRRK2-IN-1 (PubMed:26824392, PubMed:28720718).|||Lysosome|||Mitochondrion outer membrane|||Perikaryon|||Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:26824392, PubMed:29125462, PubMed:28720718, PubMed:30398148, PubMed:29212815). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:30398148, PubMed:29212815, PubMed:29125462). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:30398148, PubMed:29212815). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (By similarity). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (By similarity). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (By similarity). Regulates neuronal process morphology in the intact central nervous system (CNS) (By similarity). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (By similarity). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (By similarity). Phosphorylates PRDX3 (By similarity). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (By similarity). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (By similarity). In addition, has GTPase activity via its Roc domain which regulates LRKK2 kinase activity (By similarity).|||The Roc domain mediates homodimerization and regulates kinase activity.|||The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (By similarity). It also mediates homodimerization and regulates kinase activity (By similarity).|||Ubiquitinated by TRIM1; undergoes 'Lys-48'-linked polyubiquitination leading to proteasomal degradation.|||axon|||cytoskeleton|||dendrite|||synaptic vesicle membrane http://togogenome.org/gene/10090:Psmd2 ^@ http://purl.uniprot.org/uniprot/Q3TKV1|||http://purl.uniprot.org/uniprot/Q8VDM4 ^@ Function|||Similarity|||Subunit ^@ Belongs to the proteasome subunit S2 family.|||Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP).|||Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases and few additional components including PSMD2 (By similarity). Interacts with RPGRIP1L (PubMed:26150391). Interacts with CRY1 in a KDM8-dependent manner (PubMed:30500822). Interacts (via C-terminus) with phosphatase UBLCP1 (via ubiquitin-like domain); the interaction recruits UBLCP1 to the 19S regulatory particle where it dephosphorylates 19S subunit PSMC2/RPT1 which impairs PSMC2 ATPase activity and disrupts 26S proteasome assembly (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. http://togogenome.org/gene/10090:Phactr3 ^@ http://purl.uniprot.org/uniprot/A2AHM4|||http://purl.uniprot.org/uniprot/Q6KCA9|||http://purl.uniprot.org/uniprot/Q8BYK5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosphatase and actin regulator family.|||Binds PPP1CA and actin.|||Binds PPP1CA and actin; thus inhibiting the protein phosphatase 1 (PP1) activity.|||Nucleus matrix http://togogenome.org/gene/10090:Nelfe ^@ http://purl.uniprot.org/uniprot/P19426|||http://purl.uniprot.org/uniprot/Q3UIA1 ^@ Domain|||Function|||PTM|||Polymorphism|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM NELF-E family.|||Chromosome|||Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:31399344). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (PubMed:31399344). Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA (By similarity).|||Nucleus|||Phosphorylated by the P-TEFb complex at sites next to its RNA recognition motif, promoting its release from chromatin.|||Poly-ADP-ribosylated by PARP1, thereby preventing RNA-binding and relieving transcription pausing.|||Sumoylated.|||The NELF complex is composed of NELFA, NELFB, NELFCD and NELFE (By similarity). Interacts with NELFB (PubMed:26010750).|||The RRM domain interacts with RNA, and is essential for NELF complex function. It is however not required for the NELF complex formation (By similarity).|||The length of the RD repeats is variable. http://togogenome.org/gene/10090:Fam162a ^@ http://purl.uniprot.org/uniprot/Q9D6U8 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UPF0389 family.|||Induced by hypoxia.|||Interacts with HSP90AB1; HSP90AB1 is essential for FAM162A mitochondrial localization and pro-apoptotic activity (By similarity). Interacts with VDAC2; the interaction is probably involved in inducing mitochondrial permeability transition (By similarity).|||Mitochondrion membrane|||Proposed to be involved in regulation of apoptosis; the exact mechanism may differ between cell types/tissues (PubMed:15082785). May be involved in hypoxia-induced cell death of transformed cells implicating cytochrome C release and caspase activation (such as CASP9) and inducing mitochondrial permeability transition (PubMed:15082785). May be involved in hypoxia-induced cell death of neuronal cells probably by promoting release of AIFM1 from mitochondria to cytoplasm and its translocation to the nucleus; however, the involvement of caspases has been reported conflictingly (PubMed:17316997). http://togogenome.org/gene/10090:Mup2 ^@ http://purl.uniprot.org/uniprot/A2AKN9 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Igsf23 ^@ http://purl.uniprot.org/uniprot/B2RTN2 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||May be involved in osteoclast differentiation. http://togogenome.org/gene/10090:Cpz ^@ http://purl.uniprot.org/uniprot/Q8R4V4 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase M14 family.|||Cleaves substrates with C-terminal arginine residues. Probably modulates the Wnt signaling pathway, by cleaving some undefined protein. May play a role in cleavage during prohormone processing (By similarity).|||Inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGTA) and guanidinoethylmercaptosuccinic acid (GEMSA). Inhibited by chelating agents such as EDTA and EGTA (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Als2cl ^@ http://purl.uniprot.org/uniprot/Q60I26 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a guanine nucleotide exchange factor (GEF) for Rab5 GTPase. Regulates the ALS2-mediated endosome dynamics (By similarity).|||Cytoplasm|||Expressed in heart, lung, liver and kidney.|||Homodimer. Forms a heteromeric complex with ALS2. Interacts with ALS2 and RAB5A.|||Intron retention. http://togogenome.org/gene/10090:Irx5 ^@ http://purl.uniprot.org/uniprot/Q9JKQ4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TALE/IRO homeobox family.|||Disruption causes increased KCND2 potassium-channel expression in endocardial myocardium leading to abolition of the cardiac repolarization gradient, a selective increase of the major cardiac repolarization current, I(to,f), and increased susceptibility to arrhythmias.|||Establishes the cardiac repolarization gradient by its repressive actions on the KCND2 potassium-channel gene. Required for retinal cone bipolar cell differentiation. May regulate contrast adaptation in the retina and control specific aspects of visual function in circuits of the mammalian retina. Involved in craniofacial and gonadal development (By similarity). Modulates the migration of progenitor cell populations in branchial arches and gonads by repressing CXCL12.|||In 9.5 dpc embryos, expressed in the rhombencephalon, metencephalon, and in the cephalic mesoderm surround the optic vesicle. By 12.5 dpc, expression continues in the mesenchyme and also begins in subsets of cells in the neuroretina, becoming expressed in the retinal inner neuroblast layers by 16.5 dpc. Expressed in developing bipolar cells during retinal development starting at postnatal day 5, and expressed in a subset of cone bipolar cells in the mature retina. Also expressed along the spinal cord, in the ventricular layer, in motor neurons and in the proximal limb buds during embryonic development. Expressed in the developing heart in the endocardium that lines the heart chambers.|||Not expressed in the developing metanephric kidney or adult kidney.|||Nucleus http://togogenome.org/gene/10090:Ddx42 ^@ http://purl.uniprot.org/uniprot/Q810A7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent RNA helicase. Binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. Unwinding is promoted in the presence of single-strand binding proteins. Mediates also RNA duplex formation thereby displacing the single-strand RNA binding protein. ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands. Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2. Relocalizes TP53BP2 to the cytoplasm.|||Belongs to the DEAD box helicase family. DDX42 subfamily.|||Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A/SF3B14B, and DDX42/SF3B125. Interacts (via the C-terminus) with TP53BP2; the interaction is not inhibitied by TP53BP2 ubiquitination and is independent of p53/TP53.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Cerk ^@ http://purl.uniprot.org/uniprot/Q8K4Q7 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate (PubMed:16269826). Acts efficiently on natural and analog ceramides (C6, C8, C16 ceramides, and C8-dihydroceramide), to a lesser extent on C2-ceramide and C6-dihydroceramide, but not on other lipids, such as various sphingosines (PubMed:16269826). Shows a greater preference for D-erythro isomer of ceramides (By similarity). Binds phosphoinositides (By similarity).|||Cell membrane|||Cytoplasm|||High level expression in heart, brain, testis and pancreas; low expression in spleen, liver and lung; not detected in skeletal muscle.|||Highly expressed at 7 dpc and decreases rapidly thereafter. http://togogenome.org/gene/10090:Arl14ep ^@ http://purl.uniprot.org/uniprot/Q8BIX3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Interacts with ARL14 and MYO1E.|||May be due to intron retention.|||Through its interaction with ARL14 and MYO1E, may connect MHC class II-containing cytoplasmic vesicles to the actin network and hence controls the movement of these vesicles along the actin cytoskeleton in dendritic cells. http://togogenome.org/gene/10090:Hoxd9 ^@ http://purl.uniprot.org/uniprot/P28357 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Abd-B homeobox family.|||Expressed in the developing limb buds. Expressed in the posterior-most regions of the fetus. Strongly expressed in 12.5 day old fetuses in both spinal cord and pre-vertebral column with an anterior boundary of expression lying at the level of the first lumbar pre-vertebrae.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. http://togogenome.org/gene/10090:Or13c7c ^@ http://purl.uniprot.org/uniprot/Q9QZ20 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cox15 ^@ http://purl.uniprot.org/uniprot/Q8BJ03 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the COX15/CtaA family.|||May be involved in the biosynthesis of heme A.|||Mitochondrion membrane http://togogenome.org/gene/10090:Fhit ^@ http://purl.uniprot.org/uniprot/O89106 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in heart, brain, lung and skeletal muscle. Particularly strong expression in liver, testis and kidney, where it is confined to the tubular epithelium.|||Homodimer. Interacts with UBE2I. Interacts with MDM2. Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1 (By similarity).|||Mitochondrion|||No visible phenotype at birth, but about 30% of the mice lacking one or both copies of Fhit died for unknown reasons at an age of about 19 months. This might be due to increased susceptibility to infections. Mice lacking one or both copies of Fhit show increased susceptibility to carcinogens.|||Nucleus|||Phosphorylation at Tyr-114 by SRC is required for induction of apoptosis.|||Possesses dinucleoside triphosphate hydrolase activity (By similarity). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP (By similarity). Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP (By similarity). Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate (By similarity). Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By similarity). Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate (By similarity). Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate (By similarity). Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5 (By similarity). Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways (By similarity). Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis (By similarity). Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity (By similarity). Functions as tumor suppressor (PubMed:10758156, PubMed:11517343). http://togogenome.org/gene/10090:Pnpt1 ^@ http://purl.uniprot.org/uniprot/Q8K1R3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the polyribonucleotide nucleotidyltransferase family.|||Cytoplasm|||Homotrimer; in free form. Homooligomer. Component of the mitochondrial degradosome (mtEXO) complex which is a heteropentamer containing 2 copies of SUPV3L1 and 3 copies of PNPT1. As part of the mitochondrial degradosome complex, interacts with GRSF1 in an RNA-dependent manner; the interaction enhances the activity of the complex. Interacts with TCL1A; the interaction has no effect on PNPT1 exonuclease activity.|||Mice show alteration in the mechanisms of polycistronic mtRNAs processing in mitochondria, resulting in fewer mature mtRNAs and a reduction in electron transport chain (ETC) components formation.|||Mitochondrion intermembrane space|||Mitochondrion matrix|||RNA-binding protein implicated in numerous RNA metabolic processes. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Involved in the degradation of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules (By similarity). Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Also plays a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA. http://togogenome.org/gene/10090:Rhbdl1 ^@ http://purl.uniprot.org/uniprot/Q3USF1|||http://purl.uniprot.org/uniprot/Q8VC82 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S54 family.|||May be involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors.|||Membrane http://togogenome.org/gene/10090:Tmprss7 ^@ http://purl.uniprot.org/uniprot/Q8BIK6 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Cell membrane|||Differs at the N-terminus for unknown reasons.|||Expressed in brain, eye, testis, skin, epididymis and salivary gland with lower levels in heart, skeletal muscle, thymus, ovary, prostate and uterus.|||Forms a heterodimer with SERPINA5.|||N-glycosylated.|||Serine protease which preferentially hydrolyzes peptides with Arg at the P1 position. http://togogenome.org/gene/10090:Defa3 ^@ http://purl.uniprot.org/uniprot/P28310 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha-defensin family.|||Paneth cells of the small bowel.|||Probably contributes to the antimicrobial barrier function of the small bowel mucosa.|||Secreted http://togogenome.org/gene/10090:Arih1 ^@ http://purl.uniprot.org/uniprot/Q9Z1K5 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity. Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1.|||Belongs to the RBR family. Ariadne subfamily.|||Cajal body|||Cytoplasm|||E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets. The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2. E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes. Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear. According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest. According to another report EIF4E2 ubiquitination leads to its subsequent degradation. Acts as the ligase involved in ISGylation of EIF4E2. In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, may act in nuclear subcellular localization and nuclear morphology.|||Interacts (via the first RING-type zinc finger) with UBE2L3. Associates with cullin-RING ubiquitin ligase (CRL) complexes containing CUL1, CUL2 and CUL3. Interacts with neddylated CUL1. Interacts with neddylated CUL2. Interacts with neddylated CUL3. Interacts with neddylated CUL4A.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate.|||Nucleus|||The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.|||Widely expressed. http://togogenome.org/gene/10090:Pappa2 ^@ http://purl.uniprot.org/uniprot/E9PZ87|||http://purl.uniprot.org/uniprot/Q505G3|||http://purl.uniprot.org/uniprot/Q8BJG6 ^@ Caution|||Similarity ^@ Belongs to the peptidase M43B family.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Acvr1b ^@ http://purl.uniprot.org/uniprot/Q3TZF1|||http://purl.uniprot.org/uniprot/Q61271 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activin receptor type-2 (ACVR2A or ACVR2B) activates the type-1 receptor through phosphorylation of its regulatory GS domain.|||Autophosphorylated. Phosphorylated by activin receptor type-2 (ACVR2A or ACVR2B) in response to activin-binding at serine and threonine residues in the GS domain. Phosphorylation of ACVR1B by activin receptor type-2 regulates association with SMAD7 (By similarity).|||Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.|||Cell membrane|||Forms an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B) (By similarity). Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:10681527). Interacts with SMAD2 and SMAD3 (By similarity). Interacts with SMAD7 (By similarity). Interacts with FKBP1A (By similarity). Interacts with IGSF1 (By similarity). Interacts with CRIPTO (By similarity). Interacts with TDP2 (PubMed:18039968). Interacts with TSC22D1/TSC-22 (By similarity).|||Leads to hair loss.|||Membrane|||The GS domain is a 30-amino-acid sequence adjacent to the N-terminal boundary of the kinase domain and highly conserved in all other known type-1 receptors but not in type-2 receptors. The GS domain is the site of activation through phosphorylation by the II receptors (By similarity).|||Transmembrane serine/threonine kinase activin type-1 receptor forming an activin receptor complex with activin receptor type-2 (ACVR2A or ACVR2B). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating a many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, type-2 receptors (ACVR2A and/or ACVR2B) act as a primary activin receptors whereas the type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor such as ACVR1B. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor. ACVR1B also phosphorylates TDP2.|||Ubiquitinated.|||Ubiquitinated. Level of ubiquitination is regulated by the SMAD7-SMURF1 complex (By similarity). http://togogenome.org/gene/10090:Rps6ka6 ^@ http://purl.uniprot.org/uniprot/B1B0X3|||http://purl.uniprot.org/uniprot/Q7TPS0 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Constitutively activated by phosphorylation at Ser-252, Ser-392, and Ser-409 in serum-starved cells. Does not require growth factor stimulation for significant kinase activity (By similarity).|||Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis.|||Forms a complex with MAPK3/ERK1 but not with MAPK9 or MAPK14 in serum-starved cells.|||Nucleus|||Phosphorylated at Ser-252, Ser-392, and Ser-409 in serum-starved cells.|||cytosol http://togogenome.org/gene/10090:Cd300lb ^@ http://purl.uniprot.org/uniprot/Q3U497 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an activating immune receptor in mast cells through its interaction with ITAM-bearing adapter TYROBP.|||Belongs to the CD300 family.|||Cell membrane|||Expressed in myeloid cells (at protein level).|||Interacts with TYROBP, which enhances cell surface expression and activation properties. May interact with HCST.|||N-glycosylated. http://togogenome.org/gene/10090:Gsr ^@ http://purl.uniprot.org/uniprot/P47791 ^@ Cofactor|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.|||Binds 1 FAD per subunit.|||Cytoplasm|||Each subunit can be divided into 4 domains that are consecutive along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH, respectively. Domain 4 forms the interface.|||Homodimer; disulfide-linked.|||Maintains high levels of reduced glutathione in the cytosol.|||Mitochondrion|||The active site is a redox-active disulfide bond. http://togogenome.org/gene/10090:Clptm1 ^@ http://purl.uniprot.org/uniprot/Q8VBZ3 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the CLPTM1 family.|||Involved in GABAergic but not glutamatergic transmission (PubMed:29395912). Binds and traps GABAA receptors in the endoplasmic reticulum (ER) (PubMed:29395912). Modulates postsynaptic GABAergic transmission, and therefore inhibitory neurotransmission, by reducing the plasma membrane expression of these receptors (PubMed:29395912). Altered GABAergic signaling is one among many causes of cleft palate (PubMed:29395912). Might function as a lipid scramblase, translocating lipids in membranes from one leaflet to the other one (By similarity). Required for efficient glycosylphosphatidylinositol (GPI) inositol deacylation in the ER, which is a crucial step to switch GPI-anchored proteins (GPI-APs) from protein folding to transport states (By similarity). May play a role in T-cell development (PubMed:9218588).|||Membrane|||Mice overexpressing Clptm1 exhibit an aberrant development of thymocytes.|||Ubiquitously expressed in mouse embryo.|||Widely expressed (PubMed:9218588, PubMed:9828125). Expressed by subcapsular and outer cortical thymic cells (PubMed:9218588). http://togogenome.org/gene/10090:Cdk15 ^@ http://purl.uniprot.org/uniprot/Q3V3A1 ^@ Function|||Similarity ^@ Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.|||Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at 'Thr-34'. http://togogenome.org/gene/10090:Cyp39a1 ^@ http://purl.uniprot.org/uniprot/A0A3B2W4C8|||http://purl.uniprot.org/uniprot/A0A3B2WCK5|||http://purl.uniprot.org/uniprot/Q544S6|||http://purl.uniprot.org/uniprot/Q9JKJ9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A cytochrome P450 monooxygenase involved in neural cholesterol clearance through bile acid synthesis. Catalyzes 7-alpha hydroxylation of (24S)-hydroxycholesterol, a neural oxysterol that is metabolized to bile acids in the liver (PubMed:10748047). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:10748047).|||Belongs to the cytochrome P450 family.|||Endoplasmic reticulum membrane|||Liver specific. Hepatic expression is sexually dimorphic (female > male).|||Microsome membrane http://togogenome.org/gene/10090:Or10ak9 ^@ http://purl.uniprot.org/uniprot/K7N684 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Smarca5 ^@ http://purl.uniprot.org/uniprot/Q91ZW3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SNF2/RAD54 helicase family. ISWI subfamily.|||Chromosome|||Component of the ACF-5 ISWI chromatin-remodeling complex (also called the ACF/WCRF complex) at least composed of SMARCA5/SNF2H and BAZ1A/ACF1, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (By similarity). Within the complex interacts with BAZ1A/ACF1; the interaction is direct and is required to slide nucleosomes from end to center positions on a DNA template in an ATP-dependent manner (By similarity). Component of the CHRAC ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H, BAZ1A/ACF1, CHRAC1 and POLE3; the complex preferentially binds DNA through the CHRAC1-POLE3 heterodimer and possesses ATP-dependent nucleosome-remodeling activity (By similarity). Within the complex interacts with BAZ1A/ACF1; the interaction is direct and promotes the interaction with the POLE3-CHRAC1 heterodimer (By similarity). Within the complex interacts with the POLE3-CHRAC1 heterodimer; the interaction is direct and enhances nucleosome sliding activity by the SMARCA5/SNF2H and BAZ1A/ACF1 interaction (By similarity). Neither POLE3 nor CHRAC1 enhances nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex (By similarity). Component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex) at least composed of SMARCA5/SNF2H and BAZ1B/WSTF, which regulates the spacing of histone octamers on the DNA template to facilitate access to DNA (PubMed:11980720). Within the complex interacts with BAZ1B/WSTF (PubMed:19092802). Component of the NoRC-5 ISWI chromatin-remodeling complex (also called the NoRC chromatin-remodeling complex) at least composed of SMARCA5/SNF2H and BAZ2A/TIP5; the complex suppresses rDNA transcription by a combination of nucleosome remodeling, histone deacetylation, and DNA methylation (PubMed:11532953, PubMed:12198165). Within the complex interacts with BAZ2A/TIP5 (PubMed:12198165). Within the complex interacts with HDAC1 (PubMed:12198165). Component of the BRF-5 ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H and BAZ2B (By similarity). Within the complex interacts with BAZ2B (By similarity). Component of the NURF-5 ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H and BPTF (By similarity). Within the complex interacts with BPFT (By similarity). Component of the CERF-5 ISWI chromatin-remodeling complex at least composed of SMARCA5/SNF2H and CECR2 (By similarity). Within the complex interacts with CECR2 (By similarity). Component of the RSF-5 ISWI chromatin-remodeling complex (also called the RSF complex) at least composed of SMARCA5/SNF2H and RSF1 (By similarity). Within the complex interacts with RSF1 (By similarity). Interacts with the cohesin complex component RAD21; the interaction is direct (By similarity). Interacts with the NuRD complex components HDAC2, RBBP4 and CHD4; the interactions are direct (By similarity). Interacts with PCNA (By similarity). Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 which positively regulates RNA polymerase III transcription (By similarity). Interacts with MYO1C (PubMed:16514417). Interacts with BEND3 (By similarity). Interacts with SIRT6; promoting recruitment to DNA damage sites (By similarity).|||Expressed in CD34-positive erythrocyte progenitor cells. Down-regulated upon differentiation.|||Helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity (By similarity). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair; this may require intact histone H4 tails (PubMed:11532953, PubMed:11980720, PubMed:12198165). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:11532953, PubMed:11980720, PubMed:12198165). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (By similarity). The BAZ1A/ACF1-, BAZ1B/WSTF-, BAZ2A/TIP5- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner (PubMed:11532953, PubMed:11980720, PubMed:12198165). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (By similarity). Binds to core histones together with RSF1, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (By similarity). Involved in DNA replication and together with BAZ1A/ACF1 is required for replication of pericentric heterochromatin in S-phase (By similarity). Probably plays a role in repression of RNA polymerase I dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter (PubMed:12198165). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I and RNA polymerase III transcription, mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes (PubMed:19092802). Essential component of the NoRC-5 ISWI chromatin-remodeling complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (PubMed:11532953, PubMed:12198165, PubMed:12368916). Required for embryonic development and differentiation, and the proliferation of early blastocyst-derived stem cells (PubMed:14617767).|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Xylb ^@ http://purl.uniprot.org/uniprot/Q3TNA1 ^@ Function|||Similarity|||Subunit ^@ Belongs to the FGGY kinase family.|||Monomer.|||Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis. http://togogenome.org/gene/10090:Dusp18 ^@ http://purl.uniprot.org/uniprot/Q8VE01 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Can dephosphorylate single and diphosphorylated synthetic MAPK peptides, with preference for the phosphotyrosine and diphosphorylated forms over phosphothreonine. In vitro, dephosphorylates p-nitrophenyl phosphate (pNPP).|||Cytoplasm|||Mitochondrion inner membrane|||Nucleus http://togogenome.org/gene/10090:Slc7a3 ^@ http://purl.uniprot.org/uniprot/P70423 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.|||Cell membrane|||Expressed in adult brain and in a wide variety of embryonic tissues.|||N-glycosylated.|||Uniporter that mediates the uptake of cationic L-amino acids such as L-arginine, L-lysine and L-ornithine (PubMed:9334265). The transport is sodium ions- and pH-independent, moderately trans-stimulated and is mediated by passive diffusion (PubMed:9334265). http://togogenome.org/gene/10090:Fcnb ^@ http://purl.uniprot.org/uniprot/O70497 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ficolin lectin family.|||Homotrimer. Interacts with elastin. Interacts with MASP1 and MASP2.|||May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc-binding lectin (By similarity).|||Secreted|||The fibrinogen-like domain (FBG) contains calcium-binding sites that may be involved in carbohydrate binding. http://togogenome.org/gene/10090:Smpx ^@ http://purl.uniprot.org/uniprot/Q9DC77 ^@ Function|||Similarity|||Tissue Specificity ^@ Abundantly expressed in heart and skeletal muscle. Expression is increased by passive stretch.|||Belongs to the SMPX family.|||Plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair. http://togogenome.org/gene/10090:Plekho1 ^@ http://purl.uniprot.org/uniprot/Q9JIY0 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ C-terminal fragments could be released during apoptosis via caspase-3-dependent cleavage.|||Cell membrane|||Cytoplasm|||Heterodimer or homodimer. Interacts with CK2 and actin capping subunits (capping protein CP-alpha and CP-beta). CKIP1 and CK2 together inhibit the activity of actin capping protein at the barbed ends of actin filaments. Interacts with ATM, IFP35, JUN, JUND, NMI and PI3K. Interacts with AKT1, AKT2 and AKT3 (each isozyme of PKB), PtdIns(3,5)P2, PtdIns(4,5)P2 and PtdIns(3,4,5)P2 (By similarity).|||Nucleus|||Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP). May function to target CK2 to the plasma membrane thereby serving as an adapter to facilitate the phosphorylation of CP by protein kinase 2 (CK2). Appears to target ATM to the plasma membrane. Appears to also inhibit tumor cell growth by inhibiting AKT-mediated cell-survival. Also implicated in PI3K-regulated muscle differentiation, the regulation of AP-1 activity (plasma membrane bound AP-1 regulator that translocates to the nucleus) and the promotion of apoptosis induced by tumor necrosis factor TNF. When bound to PKB, it inhibits it probably by decreasing PKB level of phosphorylation (By similarity). http://togogenome.org/gene/10090:Tent5b ^@ http://purl.uniprot.org/uniprot/Q8C152 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TENT family.|||Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group in an ATP hydrolysis-dependent manner. May be involved in maintaining the translation efficiency of at least some genes through preventing degradation of their mRNAs. Prefers RNA molecules that are adenosine-rich close to 3'-end. In addition, may inhibit cell proliferation and cell cycle progression through ubiquitination of beta-catenin/CTNNB1.|||Cytoplasm|||It is uncertain whether Met-1 or Met-2 is the initiator.|||Nucleus http://togogenome.org/gene/10090:Ebna1bp2 ^@ http://purl.uniprot.org/uniprot/Q9D903 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EBP2 family.|||Interacts with WDR46.|||Required for the processing of the 27S pre-rRNA.|||nucleolus http://togogenome.org/gene/10090:Cbx6 ^@ http://purl.uniprot.org/uniprot/Q9DBY5 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Component of a PRC1-like complex. Distinct PRC1-like core complexes are composed of a RING1 subunit (RING1B or RING1A), one of the six PCGF proteins (PCGF1-6), one PHC protein (PHC1-3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8). Interacts with PCGF1, PCGF2, PCGF3, BMI1, PCGF5, PCGF6, RING1 and RNF2. May interact with H3C15 and H3C1 (By similarity). Interacts (via chromodomain) with single-stranded RNA (ssRNA) (PubMed:16537902).|||Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Possibly contributes to the target selectivity of the PRC1 complex by binding specific regions of chromatin (By similarity). Recruitment to chromatin might occur in an H3K27me3-independent fashion (PubMed:22226355, PubMed:16537902). May have a PRC1-independent function in embryonic stem cells (PubMed:22226355).|||Expressed in mouse embryonic stem cells.|||Nucleus|||Ubiquitinated. Ubiquitination regulates the function of the Polycomb group (PcG) multiprotein PRC1-like complex. Deubiquitinated by USP26. http://togogenome.org/gene/10090:Mcph1 ^@ http://purl.uniprot.org/uniprot/Q7TT79 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ BRCT domain 1 is required to prevent abnormal chromosome condensation. It binds directly to the SWI-SNF chromatin remodeling complex (By similarity).|||BRCT domains 2 and 3 recognize phosphoserine/phosphothreonine marks on proteins with high selectivity, and mediate interaction with phosphorylated CDC27. They also mediate the dual recognition of phosphoserine and phosphotyrosine in the C-terminal tail of histone H2AX (By similarity).|||High levels of expression are found in the developing forebrain and, in particular, in the walls of the lateral ventricles.|||Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex (By similarity).|||Interacts with CDC27 and maybe other components of the APC/C complex. Interacts with histone variant H2AX under DNA damage conditions (By similarity).|||centrosome http://togogenome.org/gene/10090:Or5p68 ^@ http://purl.uniprot.org/uniprot/Q8VEW5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Tgfb1 ^@ http://purl.uniprot.org/uniprot/P04202|||http://purl.uniprot.org/uniprot/Q3UNK5 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Expressed in cardiomyocytes (PubMed:26858265). Weakly expressed in the mammary glands, with a slight increase of expression following onset of involution (PubMed:19745830).|||Homodimer; disulfide-linked (By similarity). Interacts with the serine proteases, HTRA1 and HTRA3: the interaction with either inhibits TGFB1-mediated signaling and the HTRA protease activity is required for this inhibition (PubMed:14973287, PubMed:15206957). May interact with THSD4; this interaction may lead to sequestration by FBN1 microfibril assembly and attenuation of TGFB signaling (PubMed:21880733). Interacts with CD109, DPT and ASPN. Interacts with EFEMP2 (By similarity). Interacts with TSKU; the interaction contributes to regulation of the hair cycle (PubMed:22995554).|||Homodimer; disulfide-linked (By similarity). Interacts with transforming growth factor beta-1 (TGF-beta-1) chain; interaction is non-covalent and maintains TGF-beta-1 in a latent state; each latency-associated peptide (LAP) monomer interacts with TGF-beta-1 in the other monomer (By similarity). Interacts with LTBP1; leading to regulation of TGF-beta-1 activation (By similarity). Interacts with LRRC32/GARP; leading to regulation of TGF-beta-1 activation on the surface of activated regulatory T-cells (Tregs) (By similarity). Interacts with LRRC33/NRROS; leading to regulation of TGF-beta-1 activation in macrophages and microglia (PubMed:29909984). Interacts (via cell attachment site) with integrins ITGAV and ITGB6 (ITGAV:ITGB6), leading to release of the active TGF-beta-1 (PubMed:10025398). Interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction (PubMed:14985127). Interacts with HSP90AB1; inhibits latent TGFB1 activation.|||Homodimer; disulfide-linked.|||Homodimer; disulfide-linked. Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction.|||Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (PubMed:22781750, PubMed:29909984). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:29909984). TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:10025398) (By similarity). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules' (PubMed:29909984). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (PubMed:22781750). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (PubMed:18368049). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (PubMed:18368049). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (PubMed:18368049). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (By similarity). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (PubMed:33548622). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity).|||N-glycosylated. Deglycosylation leads to activation of Transforming growth factor beta-1 (TGF-beta-1); mechanisms triggering deglycosylation-driven activation of TGF-beta-1 are however unclear.|||Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:29909984). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:29909984). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (PubMed:29909984). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (By similarity). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:10025398).|||Secreted|||The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104.|||The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif locates to a long loop in the arm domain called the bowtie tail. Integrin-binding stabilizes an alternative conformation of the bowtie tail. Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1.|||Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.|||Transforming growth factor beta-1 proprotein: The precursor proprotein is cleaved in the Golgi apparatus by FURIN to form Transforming growth factor beta-1 (TGF-beta-1) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-1 inactive.|||extracellular matrix http://togogenome.org/gene/10090:Alg9 ^@ http://purl.uniprot.org/uniprot/Q8VDI9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 22 family.|||Catalyzes the transfer of mannose from Dol-P-Man to lipid-linked oligosaccharides.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Pgap6 ^@ http://purl.uniprot.org/uniprot/Q9ESN3 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM8 family.|||Cell membrane|||Embryonic lethal with anterior-posterior axis formation defects in embryos from 6.7 dpc on until cessation of development at latest in 10 dpc.|||Glycosylated.|||Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchor proteins (GPI-AP). Has phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI. Required for the shedding of the GPI-AP CRIPTO, but not CFC1, at the cell surface. Shedding of CRIPTO modulates Nodal signaling by allowing soluble CRIPTO to act as a Nodal coreceptor on other cells. Also indirectly involved in the translocation of RAC1 from the cytosol to the plasma membrane by maintaining the steady state amount of CAV1-enriched plasma membrane subdomains, stabilizing RAC1 at the plasma membrane.|||Lysosome membrane http://togogenome.org/gene/10090:Dnah8 ^@ http://purl.uniprot.org/uniprot/Q91XQ0 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the dynein heavy chain family.|||Consists of at least two heavy chains and a number of intermediate and light chains.|||Cytoplasm|||Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.|||Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly.|||Homozygous knockout male mice are sterile due to diminished sperm movement (PubMed:32619401). Sperm flagella show disorganized microtubules and outer dense fibers resulting in significantly higher rates of abnormal flagella (PubMed:32619401).|||Isoform 1 and/or isoform 2 are expressed in spermatocytes and mature sperm (at protein level). Testis-specific. Accumulates exclusively in mid to late spermatocytes.|||May be due to an intron retention.|||flagellum axoneme http://togogenome.org/gene/10090:Fgl2 ^@ http://purl.uniprot.org/uniprot/P12804 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Constitutively expressed in cytotoxic T-cells.|||Converts prothrombin to thrombin.|||Homotetramer; disulfide-linked.|||In macrophages, during infection by mouse hepatitis virus strain 3 (MHV-3).|||Secreted http://togogenome.org/gene/10090:Tas2r116 ^@ http://purl.uniprot.org/uniprot/Q7M713 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane|||Putative taste receptor which may play a role in the perception of bitterness.|||Several bitter taste receptors are expressed in a single taste receptor cell. http://togogenome.org/gene/10090:Mast3 ^@ http://purl.uniprot.org/uniprot/A0A1D5RM97|||http://purl.uniprot.org/uniprot/Q3U214 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm|||In brain cortex, expressed in postmitotic excitatory neurons at 14.5-16.5 dpc.|||Interacts with PTEN. http://togogenome.org/gene/10090:Ttl ^@ http://purl.uniprot.org/uniprot/P38585 ^@ Function|||Similarity|||Subunit ^@ Belongs to the tubulin--tyrosine ligase family.|||Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin.|||Monomer. http://togogenome.org/gene/10090:Or5p4 ^@ http://purl.uniprot.org/uniprot/Q8VGI5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Higd1c ^@ http://purl.uniprot.org/uniprot/Q1XG80|||http://purl.uniprot.org/uniprot/Q76I25 ^@ Subcellular Location Annotation ^@ Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Nub1 ^@ http://purl.uniprot.org/uniprot/P54729 ^@ Developmental Stage|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By interferon.|||Directly interacts with NEDD8 and PSMD4/S5a, a member of the regulatory subunit of the 26S proteasome. Interacts with AIPL1. The interaction with UBD via UBA domains facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates UBD degradation and that of its conjugates (By similarity).|||Nucleus|||Specific down-regulator of the NEDD8 conjugation system. Recruits NEDD8, UBD, and their conjugates to the proteasome for degradation (By similarity).|||Strongest expression at 7 dpc. Marked decrease 11, 15 and 17 dpc. http://togogenome.org/gene/10090:Ankrd27 ^@ http://purl.uniprot.org/uniprot/Q3UMR0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Cytoplasmic vesicle|||Cytoplasmic vesicle membrane|||Early endosome|||Interacts with RAB21 (GDP-bound form), VPS29, KIF5A, KIF5C, GOLGA4 (By similarity). Interacts with RAB32 (GTP-bound form), RAB38 (GTP-bound form), VAMP7 (PubMed:19403694, PubMed:21187289). Interacts with low affinity with RAB5 (By similarity). ANKRD27:RAB32 heterodimers can homodimerize to form tetramers (By similarity). Can interact with RAB38 or RAB32, VPS29 and VAMP7 simultaneously (By similarity). A decreased interaction with RAB32 seen in the presence of SGSM2 (By similarity).|||Late endosome|||Lysosome|||May be a guanine exchange factor (GEF) for Rab21, Rab32 and Rab38 and regulate endosome dynamics (By similarity). May regulate the participation of VAMP7 in membrane fusion events; in vitro inhibits VAMP7-mediated SNARE complex formation by trapping VAMP7 in a closed, fusogenically inactive conformation (By similarity). Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with Rab32, Rab38 and VAMP7 (PubMed:19403694, PubMed:21187289). Involved in the regulation of neurite growth; the function seems to require its GEF activity, probably towards Rab21, and VAMP7 but not Rab32/38 (PubMed:19745841, PubMed:22171327). Proposed to be involved in Golgi sorting of VAMP7 and transport of VAMP7 vesicles to the cell surface; the function seems to implicate kinesin heavy chain isoform 5 proteins, GOLGA4, RAB21 and MACF1. Required for the colocalization of VAMP7 and Rab21, probably on TGN sites (By similarity). Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with VPS29 (By similarity). Regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (PubMed:26620560).|||Melanosome http://togogenome.org/gene/10090:Rad51b ^@ http://purl.uniprot.org/uniprot/O35719 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RecA family. RAD51 subfamily.|||Expressed in a wide range of tissues.|||Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. May promote the assembly of presynaptic RAD51 nucleoprotein filaments. Binds single-stranded DNA and double-stranded DNA and has DNA-dependent ATPase activity. Part of the RAD51 paralog protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of RAD51 recruitment. BCDX2 binds predominantly to the intersection of the four duplex arms of the Holliday junction and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway.|||Nucleus|||Part of the BCDX2 complex consisting of RAD51B, RAD51C, RAD51D and XRCC2; the complex has a ring-like structure arranged into a flat disc around a central channel. The BCDX2 subcomplex RAD51B:RAD51C interacts with RAD51. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with HELQ.|||Phosphorylated on tyrosine residues by BCR-ABL. http://togogenome.org/gene/10090:Klhl31 ^@ http://purl.uniprot.org/uniprot/Q8BWA5 ^@ Function|||PTM ^@ N-terminus is methylated by METTL11A/NTM1.|||Transcriptional repressor in MAPK/JNK signaling pathway to regulate cellular functions. Overexpression inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE) (By similarity). http://togogenome.org/gene/10090:Myh14 ^@ http://purl.uniprot.org/uniprot/Q6URW6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.|||Constitutively active isoform which does not require phosphorylation of the regulatory myosin light chain for activity.|||Highest levels in lung, kidney, brain and colon, very low levels in liver and bladder and no expression in spleen or seminal vesicle (at protein level). Isoform 1 is expressed in liver, kidney and testis with low levels in skeletal muscle and heart. Isoform 1 and isoform 2 are expressed in brain and lung. Isoform 2 is the main isoform expressed in skeletal muscle and heart. Isoform 3 is limited to brain stem, cerebellum and spinal cord.|||Myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).|||Requires phosphorylation of the myosin regulatory light chain for activity.|||Survival to adulthood with no obvious defects in brain structure, lung and heart development and no evidence for defective cell division. Deletion in animals expressing only 12% of wild-type amounts of Myh10 results in an increase in cardiac myocyte hypertrophy and interstitial fibrosis compared with the Myh10 hypomorphic animal.|||The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.|||Widely expressed throughout the embryo at 11.5 dpc. Enhanced expression in the developing pituitary at 11.5 dpc. Expressed in developing lung from 13.5 dpc. At 16.5 dpc, confined to airway epithelial cells, developing sensory area of the cochlea and intestinal epithelial cells, particularly concentrated at their apical border. http://togogenome.org/gene/10090:Fcrl6 ^@ http://purl.uniprot.org/uniprot/A1YIY0 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Acts as a MHC class II receptor. When stimulated on its own, does not play a role in cytokine production or the release of cytotoxic granules by NK cells and cytotoxic CD8(+) T cells. Does not act as an Fc receptor.|||Cell membrane|||Interacts with class II MHC. http://togogenome.org/gene/10090:Rufy4 ^@ http://purl.uniprot.org/uniprot/Q3TYX8 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By IL4/interleukin-4 in dendritic cells.|||Interacts (via RUN domain) with RAB7A.|||Positively regulates macroautophagy in primary dendritic cells. Increases autophagic flux, probably by stimulating both autophagosome formation and facilitating tethering with lysosomes. Binds to phosphatidylinositol 3-phosphate (PtdIns3P) through its FYVE-type zinc finger.|||The RUN domain and the FYVE-type zinc finger are essential for its function in the positive regulation of macroautophagy.|||autophagosome http://togogenome.org/gene/10090:Taf8 ^@ http://purl.uniprot.org/uniprot/Q9EQH4 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Taube nuss' means 'empty nut' in German.|||Belongs to the TAF8 family.|||Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts with TBP, TAF1, TAF6, TAF10, TAF11 and TAF13. Component also of a small TAF complex (SMAT) containing TAF8, TAF10 and SUPT7L. Forms a heterodimer with TAF10. Interaction with TAF10 is mediated mainly via its histone fold domain while interaction with SUPT7L is via its C-terminal region.|||Cytoplasm|||Death during early embryonic development. The inner cell mass cells of mutant embryos died of apoptosis.|||Expressed ubiquitously at very low levels throughout embryonic development. Higher levels of expression seen in inner cell mass and heart.|||Low level of expression throughout the brain with slightly higher expression in the hippocampus.|||Nucleus|||The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (By similarity). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (By similarity). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (By similarity). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (By similarity). TAF8 is involved in forming the TFIID-B module, together with TAF5 (By similarity). Mediates both basal and activator-dependent transcription (By similarity). Plays a role in the differentiation of preadipocyte fibroblasts to adipocytes, however, does not seem to play a role in differentiation of myoblasts (PubMed:14580349). Required for the integration of TAF10 in the TAF complex (By similarity). May be important for survival of cells of the inner cell mass which constitute the pluripotent cell population of the early embryo (PubMed:11076765). http://togogenome.org/gene/10090:Tacr3 ^@ http://purl.uniprot.org/uniprot/P47937 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||The anchoring of this receptor to the plasma membrane is probably mediated by the palmitoylation of a cysteine residue.|||This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Scd3 ^@ http://purl.uniprot.org/uniprot/Q99PL7 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family.|||Detected in skin, but at lower levels compared to Scd1. Detected in the middlle part of the sebaceous gland, but not in hair follicle. Not detected in liver and brain.|||Endoplasmic reticulum membrane|||Expected to bind 2 Fe(2+) ions per subunit.|||Expression is increased during the first eight days (anagen) of the hair cycle in male mice, and is low during the quiescent phase (telogen) of the hair cycle. Expression is very low throughout the hair cycle in female mice.|||Microsome membrane|||Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA (PubMed:16443825, PubMed:26098370). Has a strong preference for saturated fatty acids with chain lengths of 14 or 16 carbon atoms (C14:0 and C16:0), and has only very low activity with stearatate (C18:0) (PubMed:16443825, PubMed:26098370). Required for the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides (By similarity).|||The histidine box domains are involved in binding the catalytic metal ions. http://togogenome.org/gene/10090:Prkd2 ^@ http://purl.uniprot.org/uniprot/Q8BZ03 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes. Autophosphorylation of Ser-711 and phosphorylation of Ser-707 by PKC relieves auto-inhibition by the PH domain. Catalytic activity is further increased by phosphorylation at Tyr-718 in response to oxidative stress.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.|||Cell membrane|||Cytoplasm|||Interacts (via C-terminus) with LCK. Interacts (via N-terminus and zing-finger domain 1 and 2) with PRKCD in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation.|||Phosphorylation of Ser-873 correlates with the activation status of the kinase. Ser-707 is probably phosphorylated by PKC. Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting. Phosphorylation at Ser-244, Ser-707 and Ser-711 is required for nuclear localization. Phosphorylated at Tyr-438 by ABL1 in response to oxidative stress. Phosphorylated at Tyr-718 by ABL1 specifically in response to oxidative stress; requires prior phosphorylation at Ser-707 or/and Ser-711.|||Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:17226786, PubMed:20819079). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (PubMed:17226786). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-718 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (By similarity). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (By similarity). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation. During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (PubMed:20819079). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (By similarity). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (By similarity). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (By similarity). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (By similarity). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (By similarity). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (By similarity).|||trans-Golgi network http://togogenome.org/gene/10090:Cecr2 ^@ http://purl.uniprot.org/uniprot/E9Q2Z1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the CERF-1 ISWI chromatin remodeling complex (also called the CECR2-containing remodeling factor (CERF) complex) at least composed of CECR2 and SMARCA1 (By similarity). Component of the CERF-5 ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H and CECR2 (By similarity). Within the CERF-1 and CERF-5 ISWI chromatin remodeling complexes interacts with SMARCA1 and SMARCA5/SNF2H, respectively (By similarity). Interacts with acetylated lysine residues on histone H2A and H3 (in vitro) (By similarity). Interacts with LRPPRC (By similarity).|||In embryos, predominantly expressed in neural tissues (PubMed:15640247). Expressed throughout inner ear development: expressed in the neuroepithelium, head mesenchyme and the cochlear floor (PubMed:21246654).|||Nucleus|||Perinatal death with high penetrance due to cranial neural tube defects (PubMed:15640247, PubMed:20589882). Exencephaly is frequently associated by open eyelids (PubMed:20589882). Defects may be due to misregulation of mesenchymal/ectodermal transcription factors (PubMed:20589882). Fetuses also show specific inner ear defects, such as smaller cochleae as well as rotational defects of sensory cells and extra cell rows in the inner ear reminiscent of planar cell polarity (PCP) mutants (PubMed:21246654). Mutant males non-penetrant for neural tube defects produce smaller litters: mutants have normal seminiferous epithelium morphology, sperm count, motility and morphology, but the mutant spermatozoa are compromised in their ability to fertilize oocytes (PubMed:22154806).|||Regulatory subunit of the ATP-dependent CERF-1 and CERF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (By similarity). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (By similarity). The CERF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the CERF-5 ISWI chromatin remodeling complex (By similarity). Plays a role in various processes during development: required during embryogenesis for neural tube closure and inner ear development (PubMed:15640247, PubMed:20589882, PubMed:21246654). In adults, required for spermatogenesis, via the formation of ISWI-type chromatin complexes (PubMed:22154806). In histone-modifying complexes, CECR2 recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated (By similarity). May also be involved through its interaction with LRPPRC in the integration of cytoskeletal network with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling and cytokinesis (By similarity).|||The Bromo domain recognizes and binds acetylated histones. Also recognizes and binds histones that are butyrylated. http://togogenome.org/gene/10090:Spic ^@ http://purl.uniprot.org/uniprot/Q6P3D7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Binds DNA as a monomer.|||Cell-autonomous defect in the development of red pulp macrophages, but normal monocyte and other macrophage subsets. Mice show normal trapping of red blood cells in the spleen, but fail to phagocytose these cells efficiently and develop an iron overload localized selectively to splenic red pulp.|||Controls the development of red pulp macrophages required for red blood cells recycling and iron homeostasis. Transcription factor that binds to the PU-box, a purine-rich DNA sequence (5'-GAGGA[AT]-3') that can act as a lymphoid-specific enhancer. Regulates VCAM1 gene expression.|||Expressed in lymphoid tissues, including spleen, bone marrow and thymus. According to PubMed:19037245, highly expressed in red pulp macrophages and, at lower, levels in B-cells, but not in other cells, including, monocytes, dendritic cells and other tissue macrophages. According to PubMed:10464163 expressed in pre- and mature B-cells but not in immature B-cells; according to PubMed:10187812 not expressed in pre- but predominantly in mature B-cells and at lower levels in macrophages.|||Nucleus http://togogenome.org/gene/10090:Pard6g ^@ http://purl.uniprot.org/uniprot/Q8CBL3|||http://purl.uniprot.org/uniprot/Q9JK84 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (By similarity).|||Belongs to the PAR6 family.|||Cell membrane|||Cytoplasm|||Interacts with PARD3 (Probable). Interacts with GTP-bound forms of CDC42, RHOQ/TC10 and RAC1 (By similarity). Interacts with the N-terminal part of PRKCI and PRKCZ (By similarity).|||The pseudo-CRIB domain together with the PDZ domain is required for the interaction with Rho small GTPases.|||tight junction http://togogenome.org/gene/10090:Shroom4 ^@ http://purl.uniprot.org/uniprot/Q1W617 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shroom family.|||Detected in most adult tissues examined. Expressed in brain, lung, heart, liver, kidney, muscle and ovary. Expressed throughout the brain, with high expression in the brain stem and cerebellum and weaker expression in the hypothalamus, the hippocampus and the olfactory bulb. Expressed in wide range of cell types during developpment, including vascular endothelium and the polarized epithelium of the neural tube and kidney.|||Interacts directly with F-actin.|||Probable regulator of cytoskeletal architecture that plays an important role in development. May regulate cellular and cytoskeletal architecture by modulating the spatial distribution of myosin II.|||Slight expression at 8.5 dpc, increasing till 11.5 dpc and remaining continuous thereafter, suggesting regulated expression during development.|||cytoskeleton http://togogenome.org/gene/10090:Nova2 ^@ http://purl.uniprot.org/uniprot/A0A1W2P872 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain cortex (PubMed:27223325). Expression is enriched in excitatory neuronal-linage (PubMed:30638744).|||Expression level is progressively up-regulated during neural differentiation from neural progenitor cells at 12.5 dpc to 18.5 dpc.|||Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion. It binds specifically to the sequences 5'-YCAY-3' and regulates splicing in only a subset of regulated exons (PubMed:14615540). Binding to an exonic 5'-YCAY-3' cluster changes the protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion, whereas binding to an intronic 5'-YCAY-3' cluster enhances spliceosome assembly and exon inclusion (PubMed:16041372). With NOVA1, they perform unique biological functions in different brain areas and cell types. Uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development, being essential for central nervous system development by regulating neural networks wiring (PubMed:27223325, PubMed:16041372). Regulates differentially alternative splicing on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons where is required for, respectively, development of laminar structure and motor coordination and synapse formation. Also the regulation the regulation of intron retention can sequester the trans-acting splicing factor PTBP2, acting as a variable cis-acting scaffolding platform for PTBP2 across various natural conditions (PubMed:30638744).|||Interacts with PTBP2; the interaction is direct.|||Knockouts are born indistinguishable from littermates but failed to thrive, demonstrating progressive motor dysfunction and overt motor weakness, and they die an average of 14-18 days after birth. They have agenesis of the corpus callosum, and axonal outgrowth defects specific to ventral motoneuron axons and efferent innervation of the cochlea (PubMed:27223325). Conditional knockouts in excitatory neurons die between three and four weeks old and show disorganized cortical and hippocampal CA1 and CA3 laminar structure. Conditional knockouts in inhibitory neurons show no neuronal migration or position abnormality. They display reduced thickness of CA1 stratum lacunosum-moleculare (SLM) and dentate gyrus molecular layer (PubMed:30638744). Conditional knockouts in Purkinje cells have progressive motor discoordination and cerebellar atrophy. They show a marked defect in dendritic morphology, Purkinje cells degeneration, loss of synaptic layer thickness accompanied by neuritic swelling and reduced spine density (PubMed:30638744).|||Nucleus|||The third KH domain (KH3) recognizes specifically 5'-YCAY-3'. http://togogenome.org/gene/10090:Tyk2 ^@ http://purl.uniprot.org/uniprot/E9QJS1|||http://purl.uniprot.org/uniprot/Q9R117 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.|||Deficient mice are viable and fertile but display multiple immunological defects, most prominently high sensitivity to infections and defective tumor surveillance. Absence of TYK2 results in increased resistance against allergic, autoimmune and inflammatory disease.|||Interacts (via FERM domain) with JAKMIP1. Interacts with PIK3R1; this interaction is important for cell migration.|||Phosphorylation by JAK1 at Tyr-1051 and Tyr-1052 induces kinase activation.|||The protein kinase 1 domain (also termed pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain.|||Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:11070174). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (By similarity). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:22859374). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (By similarity). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (By similarity). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (By similarity). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (By similarity). http://togogenome.org/gene/10090:Lin28b ^@ http://purl.uniprot.org/uniprot/Q45KJ6 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the lin-28 family.|||Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA. Does not act on pri-miR21. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation. This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent. Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop (By similarity). Mediates MYC-induced let-7 repression (PubMed:19211792). When overexpressed, may stimulate growth of carcinoma cell lines (By similarity).|||The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids (By similarity).|||nucleolus http://togogenome.org/gene/10090:Mylk2 ^@ http://purl.uniprot.org/uniprot/Q8VCR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.|||Cytoplasm|||Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain (By similarity).|||May interact with centrin. http://togogenome.org/gene/10090:Or2at1 ^@ http://purl.uniprot.org/uniprot/E9Q519 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ipmk ^@ http://purl.uniprot.org/uniprot/D3YWA2|||http://purl.uniprot.org/uniprot/Q7TT16 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the inositol phosphokinase (IPK) family.|||Binds two Mg(2+), but the interaction with the protein is mostly indirect.|||Inositol phosphate kinase with a broad substrate specificity. Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:15939867). Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4). Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate (By similarity). Plays an important role in MLKL-mediated necroptosis via its role in the biosynthesis of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Binding of these highly phosphorylated inositol phosphates to MLKL mediates the release of an N-terminal auto-inhibitory region, leading to activation of the kinase. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (By similarity). Required for normal embryonic development, probably via its role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6) (PubMed:15939867).|||Nucleus http://togogenome.org/gene/10090:Lgals4 ^@ http://purl.uniprot.org/uniprot/Q8K419 ^@ Domain|||Function|||Subunit|||Tissue Specificity ^@ Contains two homologous but distinct carbohydrate-binding domains.|||Epithelial cells of the embryonic and adult gastrointestinal tract. Expressed at about equal levels in colon and small intestine but much less in stomach.|||Galectin that binds lactose and a related range of sugars.|||Monomer. http://togogenome.org/gene/10090:Scn9a ^@ http://purl.uniprot.org/uniprot/B1AYL0|||http://purl.uniprot.org/uniprot/E9PW82|||http://purl.uniprot.org/uniprot/Q62205 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sodium channel (TC 1.A.1.10) family.|||Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.7/SCN9A subfamily.|||Cell membrane|||Expressed strongly in sciatic nerves, with moderate levels in kidney (PubMed:31647222). Not detected in liver, brain and muscle (PubMed:31647222).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:15123669). It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (PubMed:15314237).|||Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.|||Membrane|||Phosphorylation at Ser-1488 by PKC in a highly conserved cytoplasmic loop increases peak sodium currents.|||The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.|||The sodium channel complex consists of a large, channel-forming alpha subunit (SCN9A) regulated by one or more beta subunits (SCN1B, SCN2B, SCN3B and SCN4B) (By similarity). SCN1B and SCN3B are non-covalently associated with SCN2A. SCN2B and SCN4B are disulfide-linked to SCN2A (By similarity). Interacts with NEDD4 and NEDD4L. Interacts with the conotoxin GVIIJ (By similarity).|||Ubiquitinated by NEDD4L; which may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4.|||neuron projection http://togogenome.org/gene/10090:Arpin ^@ http://purl.uniprot.org/uniprot/Q9D0A3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associates with the Arp2/3 complex. Interacts with ARPC2; enhanced by activated RAC1. Interacts with ARPC5; the interaction is dependent on RAC1.|||Belongs to the Arpin family.|||Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence (By similarity).|||The acidic C-terminus is necessary and sufficient to inhibit ARP2/3 complex activity.|||lamellipodium http://togogenome.org/gene/10090:Urad ^@ http://purl.uniprot.org/uniprot/B9EK13|||http://purl.uniprot.org/uniprot/Q283N4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the OHCU decarboxylase family.|||Catalyzes the stereoselective decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) to (S)-allantoin.|||Peroxisome http://togogenome.org/gene/10090:Irs2 ^@ http://purl.uniprot.org/uniprot/P81122 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with PHIP.|||May mediate the control of various cellular processes by insulin.|||Skeletal muscle, lung, brain, liver, kidney, heart and spleen.|||cytosol http://togogenome.org/gene/10090:Coro1b ^@ http://purl.uniprot.org/uniprot/A2RS22|||http://purl.uniprot.org/uniprot/Q9WUM3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the WD repeat coronin family.|||Forms homooligomers, but does not form complexes with the other coronins. Interacts with Arp2/3 complex components, including ACTR2, ARPC1B and ARPC2. Binds actin (By similarity).|||Phosphorylation on Ser-2 regulates the interaction with the Arp2/3 complex and cell motility in fibroblasts. Phosphorylation does not seem to affect subcellular location (By similarity).|||Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity).|||Ubiquitous.|||cytoskeleton|||stress fiber http://togogenome.org/gene/10090:Pdhb ^@ http://purl.uniprot.org/uniprot/Q9D051 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Heterotetramer of two PDHA1 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules. Interacts with DLAT.|||Mitochondrion matrix|||The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. http://togogenome.org/gene/10090:Khdc3 ^@ http://purl.uniprot.org/uniprot/Q9CWU5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As part of the OOEP-KHDC3 scaffold, recruits BLM and TRIM25 to DNA replication forks, thereby promoting the ubiquitination of BLM by TRIM25, enhancing BLM retainment at replication forks and therefore promoting stalled replication fork restart (PubMed:29125140, PubMed:33115731). Regulates homologous recombination-mediated DNA repair via recruitment of RAD51 to sites of DNA double-strand breaks, and sustainment of PARP1 activity, which in turn modulates downstream ATM or ATR activation (PubMed:25936915, PubMed:33115731). Activation of ATM or ATR in response to DNA double-strand breaks may be cell-type specific (PubMed:25936915, PubMed:33115731). Its role in DNA double-strand break repair is independent of its role in restarting stalled replication forks (PubMed:29125140). As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:18804437, PubMed:29125140, PubMed:28992324, PubMed:31575650). Required for maintenance of euploidy during cleavage-stage embryogenesis (PubMed:19376971). Required for the formation of F-actin cytoplasmic lattices in oocytes which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning (PubMed:25208553, PubMed:31575650). Ensures proper spindle assembly by regulating the localization of AURKA via RHOA signaling and of PLK1 via a RHOA-independent process (PubMed:19376971). Required for the localization of MAD2L1 to kinetochores to enable spindle assembly checkpoint function (PubMed:19376971). Promotes neural stem cell neurogenesis and neuronal differentiation in the hippocampus (PubMed:33115731). May regulate normal development of learning, memory and anxiety (PubMed:33115731). Capable of binding RNA (PubMed:22276159).|||Belongs to the KHDC1 family.|||Chromosome|||Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and TLE6 (PubMed:18057100, PubMed:18804437, PubMed:28992324). Within the complex, interacts with NLRP5, OOEP and TLE6 (PubMed:18057100, PubMed:18804437). The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments (By similarity). Forms a scaffold complex with OOEP/FLOPED, and interacts with BLM and TRIM25 at DNA replication forks (PubMed:29125140). Interacts with PARP1; the interaction is increased following the formation of DNA double-strand breaks (PubMed:25936915). Interacts (via C-terminus) with NUMA1 (PubMed:25936915).|||Contains 1 atypical KH domain, which is still capable of binding RNA.|||Detected in ovary, but not in testis or somatic tissues. In the ovary, expressed in growing oocytes.|||Expressed in growing oocytes but diminishes in fully grown oocytes (PubMed:18057100). Detected at very low levels in morula and early blastocyst (PubMed:18057100).|||Expressed in growing oocytes, ovulated eggs and preimplantation embryos up to the morula stage and decreases markedly at the blastocyst stage (at protein level).|||Expressed in the brain at low levels during fetal development, from 13.5 dpc to 18.5 dpc, however significantly increased after birth from P1 to P60 (PubMed:33115731). Highly expressed in neural stem progenitor cells in the hippocampus after birth (PubMed:33115731).|||Induced by ultraviolet light, etoposide, doxorubicin, camptothecin and hydroxyl urea in embryonic stem cells (PubMed:25936915). Induced by etoposide and hydroxy urea in neural stem cells (PubMed:33115731).|||Mitochondrion|||Nucleus|||Phosphorylation at Ser-151 is required to promote stalled fork restart.|||Reduced fecundity and impaired preimplantation embryo development with a high incidence of aneuploidy due to abnormal spindle assembly, chromosomal misalignment and spindle assembly checkpoint inactivation (PubMed:19376971). Loss of cytoplasmic lattices and aberrant organelle distribution in oocytes (PubMed:31575650). Increase in abnormal embryonic structure and loss of the embryo following compromised post-implantation embryo development (PubMed:29125140). Knockout mice show normal brain structure and weight (PubMed:33115731). Increased DNA double-strand breaks in hippocampus neural stem cells at P1 to 1 year of age (PubMed:33115731). Reduced hippocampal neural stem cell proliferation from P7 to P60 (PubMed:33115731). Reduced differentiation of neurons and dendritic spines formation in the dentate gyrus from P13 to P66 (PubMed:33115731). Impaired hippocampus-dependent spatial learning, memory and anxiety from 2 months to 1 year of age (PubMed:33115731).|||cell cortex|||centrosome http://togogenome.org/gene/10090:Zfp800 ^@ http://purl.uniprot.org/uniprot/Q0VEE6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Csf2rb ^@ http://purl.uniprot.org/uniprot/P26955 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||Heterodimer of an alpha and a beta subunit (PubMed:10477686). The beta subunit is common to the IL3, IL5 and GM-CSF receptors. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits. Interacts with TMEM102; this interaction occurs preferentially in the absence of CSF2 (By similarity). Interacts with FCER1G; this interaction is direct (PubMed:19098920). Interacts with LYN.|||High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.|||May be phosphorylated by LYN.|||Membrane|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Krtcap2 ^@ http://purl.uniprot.org/uniprot/A0A0A0MQN1|||http://purl.uniprot.org/uniprot/Q5RL79 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KRTCAP2 family.|||Component of the oligosaccharyltransferase (OST) complex. OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits. STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity). Interacts with PSEN1 and NCSTN; indicative for an association with the gamma-secretase complex (By similarity).|||Endoplasmic reticulum membrane|||Membrane|||Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. May be involved in N-glycosylation of APP (amyloid-beta precursor protein). Can modulate gamma-secretase cleavage of APP by enhancing endoprotelysis of PSEN1. http://togogenome.org/gene/10090:Hamp ^@ http://purl.uniprot.org/uniprot/Q9EQ21 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the hepcidin family.|||Highly expressed in the liver and to a much lesser extent in the heart. Secreted in blood (PubMed:15124018).|||Interacts with SLC40A1; this interaction promotes SLC40A1 rapid ubiquitination.|||Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of SLC40A1, leading to the retention of iron in iron-exporting cells and decreased flow of iron into plasma. Controls the major flows of iron into plasma: absorption of dietary iron in the intestine, recycling of iron by macrophages, which phagocytose old erythrocytes and other cells, and mobilization of stored iron from hepatocytes.|||Regulated in response to changes in circulating iron concentrations, iron stores or the development of inflammation and iron-restricted erythropoiesis. Down-regulated following anemia induced by hemorrhage or hemolysis: down-regulation is mediated by ERFE (PubMed:12370282, PubMed:24880340, PubMed:15124018). The induction of upon inflammation is mediated by IL6 (PubMed:15124018).|||Secreted http://togogenome.org/gene/10090:Rpia ^@ http://purl.uniprot.org/uniprot/P47968 ^@ Similarity|||Tissue Specificity ^@ Belongs to the ribose 5-phosphate isomerase family.|||Widely expressed, with highest levels in testis. http://togogenome.org/gene/10090:Ttbk2 ^@ http://purl.uniprot.org/uniprot/Q3UVR3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family.|||Defects in Ttbk2 are the cause of the bartleby (bby) phenotype characterized by defects in sonic hedgehog/SHH signaling and ciliogenesis. Embryos display morphological defects at midgestation similar to those seen in mutants that lack cilia, including holoprosencephaly, twisted body axis, abnormal limb development and randomized laterality of heart looping. Mutants die at midgestation (around 10.5 dpc).|||Interacts with CEP164.|||Nucleus|||Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (By similarity).|||centriole|||cilium|||cilium basal body|||cytosol http://togogenome.org/gene/10090:Bpifb2 ^@ http://purl.uniprot.org/uniprot/Q14AV3|||http://purl.uniprot.org/uniprot/Q8C1E1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||Secreted http://togogenome.org/gene/10090:Fam227a ^@ http://purl.uniprot.org/uniprot/A0A2R8VHN9|||http://purl.uniprot.org/uniprot/Q8CA61|||http://purl.uniprot.org/uniprot/Q9D3V8 ^@ Similarity ^@ Belongs to the FAM227 family. http://togogenome.org/gene/10090:Irf3 ^@ http://purl.uniprot.org/uniprot/P70671|||http://purl.uniprot.org/uniprot/Q3U9K6 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IRF family.|||Constitutively phosphorylated on many Ser/Thr residues (PubMed:22065572). Activated following phosphorylation by TBK1 and IKBKE. Innate adapter protein MAVS, STING1 or TICAM1 are first activated by viral RNA, cytosolic DNA, and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE. These kinases then phosphorylate the adapter proteins on the pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (By similarity).|||Cytoplasm|||Double knockout with TREX1 does not show a visible phenotype.|||ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation.|||In the absence of viral infection, maintained as a monomer in an autoinhibited state. Phosphorylation by TBK1 and IKBKE disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes. Phosphorylation and activation follow the following steps: innate adapter protein MAVS, STING1 or TICAM1 are first activated by viral RNA, cytosolic DNA and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE. These kinases then phosphorylate the adapter proteins on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1. Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs.|||Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:15800576). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:15800576). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:16846591, PubMed:16979567, PubMed:20049431). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16846591, PubMed:16979567, PubMed:20049431). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591, PubMed:16979567, PubMed:20049431).|||Mitochondrion|||Monomer. Homodimer; phosphorylation-induced. Interacts (when phosphorylated) with CREBBP. Interacts with MAVS (via phosphorylated pLxIS motif). Interacts with TICAM1 (via phosphorylated pLxIS motif). Interacts with STING1 (via phosphorylated pLxIS motif). Interacts with IKBKE and TBK1. Interacts with TICAM2. Interacts with RBCK1. Interacts with HERC5. Interacts with DDX3X; the interaction allows the phosphorylation and activation of IRF3 by IKBKE. Interacts with TRIM21 and ULK1, in the presence of TRIM21; this interaction leads to IRF3 degradation by autophagy. Interacts with RIOK3; RIOK3 probably mediates the interaction of TBK1 with IRF3. Interacts with ILRUN; the interaction inhibits IRF3 binding to its DNA consensus sequence. Interacts with LYAR; this interaction impairs IRF3 DNA-binding activity. Interacts with TRAF3. Interacts with ZDHHC11; ZDHHC11 recruits IRF3 to STING1 upon DNA virus infection and thereby promotes IRF3 activation (By similarity). Interacts with HSP90AA1; the interaction mediates IRF3 association with TOMM70. Interacts with BCL2; the interaction decreases upon Sendai virus infection. Interacts with BAX; the interaction is direct, increases upon virus infection and mediates the formation of the apoptosis complex TOMM70:HSP90AA1:IRF3:BAX (By similarity). Interacts with DDX56 (By similarity). Interacts with NBR1 (By similarity).|||Nucleus|||Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation. Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction.|||Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation. Ubiquitinated by UBE3C, leading to its degradation. http://togogenome.org/gene/10090:Mipep ^@ http://purl.uniprot.org/uniprot/A6H611 ^@ Activity Regulation|||Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activity is divalent cation-dependent. It is stimulated by manganese, magnesium or calcium ions and reversibly inhibited by zinc, cobalt and iron (By similarity).|||Belongs to the peptidase M3 family.|||Binds 1 zinc ion.|||Cleaves proteins, imported into the mitochondrion, to their mature size.|||Mitochondrion matrix|||Monomer. http://togogenome.org/gene/10090:Iyd ^@ http://purl.uniprot.org/uniprot/Q9DCX8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nitroreductase family.|||Catalyzes the dehalogenation of halotyrosines such as 3-bromo-L-tyrosine, 3-chloro-L-tyrosine, 3-iodo-L-tyrosine and 3,5-diiodo-L-tyrosine (By similarity). During thyroid hormone biosynthesis, facilitates iodide salvage by catalysing the oxidative NADPH-dependent deiodination of the halogenated by-products of thyroid hormone production, monoiodotyrosine (L-MIT) and diiodotyrosine (L-DIT) (PubMed:22238141). The scavanged iodide can then reenter the hormone-producing pathways (By similarity). Acts more efficiently on 3-iodo-L-tyrosine than 3,5-diiodo-L-tyrosine (By similarity).|||Cell membrane|||Cytoplasmic vesicle membrane|||Homodimer. http://togogenome.org/gene/10090:BC048507 ^@ http://purl.uniprot.org/uniprot/Q80ZS7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.|||Belongs to the dynein light chain family.|||cytoskeleton http://togogenome.org/gene/10090:Trpc4 ^@ http://purl.uniprot.org/uniprot/Q0VB97|||http://purl.uniprot.org/uniprot/Q8BNB6|||http://purl.uniprot.org/uniprot/Q8BNT2|||http://purl.uniprot.org/uniprot/Q9QUQ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in brain (hippocampal CA1 pyramidal neurons, dentate gyrus granule cells, and cerebral cortical neurons, and in the septal nuclei and the mitral layer of olfactory bulb). Lower levels are detected in other tissues.|||Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC4 sub-subfamily.|||Cell membrane|||Homotetramer (PubMed:19070363). Heterotetramer with TRPC1 and/or TRPC5 (By similarity). Isoform alpha but not isoform beta interacts with ITPR1, ITPR2 and ITPR3 (By similarity). Interacts with NHERF1 (By similarity). Interacts with MX1 and RNF24 (By similarity). Interacts (via CIRB domain) with SESTD1 (via the spectrin 1 repeat) and SPTBN5 (via C-terminus) (By similarity). Interacts with CDH5 and CTNNB1 (By similarity). Interacts (via protein 4.1-binding domain) with EPB41L2 (By similarity). Interacts with TRPC4AP (PubMed:20458742). Interacts with PLSCR1 (PubMed:32110987).|||Membrane|||Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Acts as a cell-cell contact-dependent endothelial calcium entry channel. Has also been shown to be calcium-selective (By similarity). May also be activated by intracellular calcium store depletion. Trpc4 deficient mice lack a store-operated calcium entry in endothelial cells. http://togogenome.org/gene/10090:Msgn1 ^@ http://purl.uniprot.org/uniprot/Q9JK54 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation ^@ Involved in specifying the paraxial, but not dorsal, mesoderm. May regulate the expression of T-box transcription factors required for mesoderm formation and differentiation.|||Mutant animals die during gestation. Premature death starts around 10.5 dpc. Severe morphological abnormalities, such as enlarged tailbud, kinked neural tube posterior to forelimb buds and reduced tissue mass in the interlimb domain become obvious at 9.0 dpc and thereafter. Head and anterior body structures, including the developing heart, appeared normal. In the trunk posterior to the forelimbs, there are no identifiable somites or segment patterning, although the anterior-most somites appeared normal, with decreases in somite size and disruption of myotomal patterning in somites 8-11. There are no detectable somites beyond somite 11. At 11.5 dpc, myotomes are absent from the trunk at the interlimb level and at 12.5 dpc, muscle is absent from the hindlimbs. The few fetuses surviving beyond 14.5 and 17.5 pdc lack a tail and show a grossly normal, but very thin body with relatively normal forelimbs and hindlimbs. At this stage, all vertebrae posterior to cervical level together with ribs are absent, while all cervical vertebrae are present, although the most posterior ones are sometimes malformed and fused. Other trunk skeletal structures that originate from lateral mesoderm, such as the sternum and scapula, form quite normally.|||Nucleus|||Specifically expressed in unsegmented paraxial mesoderm and its immediate progenitors and sharply down-regulated in presumptive somites. Not detectable at 6.5 dpc. At 7.5 dpc, expressed mainly in the posterior region of the embryo, lateral to the primitive streak where presumptive progenitors of paraxial mesoderm reside. Expression is largely excluded from the midline of the primitive streak. No expression is detected in the anterior part of the embryo. At 9.0 dpc, highly expressed in the caudal presomitic mesoderm. At 11.5 dpc, the primitive streak completely regresses, expression is observed exclusively in the tailbud. Expression remains in the tailbud until 13.5 dpc and begins to disappear between 13.5 and 14.5 dpc when the tailbud loses its potential to provide paraxial mesoderm cells. http://togogenome.org/gene/10090:Taar3 ^@ http://purl.uniprot.org/uniprot/D8KZH8|||http://purl.uniprot.org/uniprot/Q5QD16 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane|||Mice lacking Taar2, Taar3, Taar4, Taar5, Taar6, Taar7a, Taar7b, Taar7d, Taar7e, Taar7f, Taar8a, Taar8b, Taar8c and Taar9 show no visible phenotype or behavioral deficits. They however show an absence of aversion to low concentrations of amines such as 2-phenylethylamine, isopentylamine, N-methylpiperidine and cadaverine.|||Olfactory receptor activated by several primary trace amines, including isoamylamine. Activated by isoamylamine and cyclohexylamine, but not to the corresponding alcohols, isoamylalcohol and cyclohexanol. This receptor is probably mediated by the G(s)-class of G-proteins which activate adenylate cyclase.|||Specifically expressed in neurons of the olfactory epithelium. http://togogenome.org/gene/10090:Sec16b ^@ http://purl.uniprot.org/uniprot/Q91XT4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SEC16 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Liver.|||Plays a role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus. Involved in peroxisome biogenesis. Regulates the transport of peroxisomal biogenesis factors PEX3 and PEX16 from the ER to peroxisomes.|||SEC16A and SEC16B are each present in multiple copies in a heteromeric complex. Interacts with TFG. Interacts with SEC13. http://togogenome.org/gene/10090:Cyb5r4 ^@ http://purl.uniprot.org/uniprot/Q3TDX8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.|||Endoplasmic reticulum|||Mice display insulin-deficient diabetes. Embryos and fetus develop normally. At 4 weeks of age, mice show have normal blood glucose levels but impaired glucose tolerance. Isolated islets have markedly impaired glucose- or arginine-stimulated insulin secretion. By 7 weeks of age, they develop severe hyperglycemia with markedly decreased serum insulin levels and nearly normal insulin tolerance. As the animals age, there is a progressive loss of beta cells in pancreatic islets, but there is no loss of alpha, delta, or PP cells. 4 week-old mice have enhanced sensitivity to the diabetogenic agent streptozotocin.|||NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS).|||Ubiquitously expressed. Isoform 2 is expressed in testis, brain, skeletal muscle and in the male germline. http://togogenome.org/gene/10090:Igsf11 ^@ http://purl.uniprot.org/uniprot/P0C673 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Functions as a cell adhesion molecule through homophilic interaction. Stimulates cell growth (By similarity).|||Highly expressed in testis and detected in kidney and adrenal gland. In brain, expressed in commissure fibers of the corpus callosum and pyramidal cell layers of the dentate gyrus and hippocampus where it is probably expressed by both neurons and glial cells.|||N-glycosylated. http://togogenome.org/gene/10090:St6galnac1 ^@ http://purl.uniprot.org/uniprot/Q9QZ39 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Glycosylated; autosialylated.|||Golgi apparatus membrane|||Protein sialyltransferase specifically expressed in goblet cells that plays a key role in intestinal host-commensal homeostasis (PubMed:35303419). Conjugates sialic acid with an alpha-2-6 linkage to N-acetylgalactosamine (GalNAc) glycan chains linked to serine or threonine in glycoproteins (PubMed:10788794). Catalyzes the formation of the sialyl-Tn (S-Tn) antigen, an antigen found in intestinal goblet cells (PubMed:35303419). Protein sialylation in globlet cells is essential for mucus integrity and is required to protect the intestinal mucus against excessive bacterial proteolytic degradation (PubMed:35303419).|||Submaxillary gland, mammary gland, spleen and colon. http://togogenome.org/gene/10090:Rnf123 ^@ http://purl.uniprot.org/uniprot/Q5XPI3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Catalytic subunit of the KPC complex that acts as E3 ubiquitin-protein ligase. Promotes the ubiquitination and proteasome-mediated degradation of CDKN1B which is the cyclin-dependent kinase inhibitor at the G0-G1 transition of the cell cycle. Also acts as a key regulator of the NF-kappa-B signaling by promoting maturation of the NFKB1 component of NF-kappa-B: acts by catalyzing ubiquitination of the NFKB1 p105 precursor, leading to limited proteasomal degradation of NFKB1 p105 and generation of the active NFKB1 p50 subunit. Functions also as an inhibitor of innate antiviral signaling mediated by RIGI and IFIH1 independently of its E3 ligase activity. Interacts with the N-terminal CARD domains of RIGI and IFIH1 and competes with the downstream adapter MAVS.|||Component of the KPC complex composed of RNF123/KPC1 and UBAC1/KPC2. Interacts with UBAC1 and CDKN1B via its N-terminal domain. Interacts with RIGI (via N-terminus) and IFIH1 (via N-terminus).|||Cytoplasm|||Ubiquitinated, leading to its degradation. Deubiquitinated by USP19, thereby stimulating CDKN1B ubiquitin-dependent degradation. http://togogenome.org/gene/10090:Klhl1 ^@ http://purl.uniprot.org/uniprot/Q9JI74 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Highly expressed in brain.|||May play a role in organizing the actin cytoskeleton of the brain cells.|||cytoskeleton http://togogenome.org/gene/10090:Eif3j2 ^@ http://purl.uniprot.org/uniprot/Q66JS6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit J family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression. This subunit binds directly within the mRNA entry channel of the 40S ribosome to the aminoacyl (A) site. It may regulate the interaction between the 43S PIC and mRNA.|||Cytoplasm|||Phosphorylated. Phosphorylation is enhanced upon serum stimulation. http://togogenome.org/gene/10090:Med11 ^@ http://purl.uniprot.org/uniprot/Q9D8C6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 11 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP (By similarity).|||Nucleus http://togogenome.org/gene/10090:Or5g27 ^@ http://purl.uniprot.org/uniprot/Q7TRA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc9a7 ^@ http://purl.uniprot.org/uniprot/Q8BLV3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.|||Cell membrane|||Golgi Na(+), K(+)/(H+) antiporter. Mediates the electoneutral influx of Na(+) or K(+) in exchange for H(+). May contribute to the regulation of Golgi apparatus volume and pH.|||Interacts with SCAMP1, SCAMP2 and SCAMP5; may participate in its shuttling from trans-Golgi network to recycling endosomes.|||N-glycosylated.|||Recycling endosome membrane|||trans-Golgi network membrane http://togogenome.org/gene/10090:2310011J03Rik ^@ http://purl.uniprot.org/uniprot/Q9D7E4 ^@ Similarity ^@ Belongs to the UPF0449 family. http://togogenome.org/gene/10090:Tacc1 ^@ http://purl.uniprot.org/uniprot/F8VQ95|||http://purl.uniprot.org/uniprot/Q6Y685 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TACC family.|||Cytoplasm|||Interacts with CH-TOG and YEATS4. Interacts with the AURKA and AURKB and AURKC. Interacts with LSM7, TDRD7 and SNRPG. Interacts with GCN5L2 and PCAF (By similarity). Interacts with the thyroid hormone receptors THRB and THRA, predominantly with isoform alpha-2. The interaction with THRA isoform alpha-1 and THRB is decreased in the presence of thyroid hormone T3 (PubMed:20078863). Interacts with RARA in the nucleus (PubMed:20078863). Also interacts with other nuclear receptors, including ESR1, NR3C1, PPARG and RXRA, preferentially in the absence of their hormonal ligands (By similarity).|||Involved in transcription regulation induced by nuclear receptors, including in T3 thyroid hormone and all-trans retinoic acid pathways. Might promote the nuclear localization of the receptors (By similarity). Likely involved in the processes that promote cell division prior to the formation of differentiated tissues.|||Midbody|||Nucleus|||centrosome http://togogenome.org/gene/10090:Grid2ip ^@ http://purl.uniprot.org/uniprot/Q0QWG9 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Interacts with C-terminus of the glutamate receptor GRID2 via PDZ domain. Isoform 2 interacts also with Profilin-2/PFN2 and with the monocarboxylate transporter SLC16A7 via PDZ domain. The interaction of isoform 2 with GRID2 is dependent on GRID2 phosphorylation by PKA.|||Isoform 1 is expressed in the cerebellum, but not in the cerebral cortex. Isoform 2 is expressed in the cell body of purkinge cells of the cerebellum and weakly expressed in the cerebrum and the brainstem as well as various nuclei of the thalamus. Isoform 2 is highly expressed in the cerebral cortex than in the cerebellum. Isoform 3 is expressed in the cerebellum and cerebrum.|||Isoform 1 shows a punctate distribution throughout the cytoplasm when expressed in COS cells, whereas isoform 2 is enriched at the edges of the plasma membranes. When expressed in cultured hippocampal neurons, isoform 1 forms clusters mainly in the dendritic shafts, whereas isoform 2 is preferentially expressed in spines.|||Isoform 2 is palmitoylated. Palmitoylation of isoform 2 is necessary for the enhanced cell surface expression of GRID2, and is also responsible for the accumulation of isoform 2 within dendritic spines. Isoform 1 and isoform 2 are differentially localized, probably modulating GRID2 signaling in neurons.|||Isoform 3 expression is maintained throughout cerebellar development, while isoform 2 expression gradually decrease following the first postnatal week.|||Not palmitoylated.|||PDZ 1 domain is responsible for cytoplasmic clustering of isoform 1.|||Postsynaptic cell membrane|||Postsynaptic scaffolding protein at the Purkinje cell synapse, where it may serve to link GRID2 with actin cytoskeleton and various signaling molecules.|||Synapse|||When Cys-3 is mutated to Ala-3, isoform 2 is not palmitoylated anymore.|||dendritic spine http://togogenome.org/gene/10090:Lipi ^@ http://purl.uniprot.org/uniprot/F6YQT7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Secreted http://togogenome.org/gene/10090:Srek1ip1 ^@ http://purl.uniprot.org/uniprot/Q4V9W2 ^@ Function|||Sequence Caution|||Subunit ^@ Contaminating sequence. Potential poly-A sequence.|||Interacts with SREK1/SFRS12.|||Possible splicing regulator involved in the control of cellular survival. http://togogenome.org/gene/10090:Ccnjl ^@ http://purl.uniprot.org/uniprot/Q5SRT8 ^@ Similarity ^@ Belongs to the cyclin family. Cyclin J subfamily. http://togogenome.org/gene/10090:Ssxb3 ^@ http://purl.uniprot.org/uniprot/Q6XAS4 ^@ Similarity ^@ Belongs to the SSX family. http://togogenome.org/gene/10090:Thoc5 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0J6|||http://purl.uniprot.org/uniprot/Q8BKT7 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. THOC5 in conjunction with ALYREF/THOC4 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in transcription elongation and genome stability. Involved in alternative polyadenylation site choice by recruiting CPSF6 to 5' region of target genes; probably mediates association of the TREX and CFIm complexes.|||Belongs to the THOC5 family.|||Cytoplasm|||Embryonic lethality seen before day 5.5 of embryonic development (E5.5).|||Interacts with phosphorylated CSF1R (PubMed:10597251). Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with ALYREF/THOC4, and THOC7. Interacts (via N-terminus) with the NTF2 domain of NXF1 (By similarity). Forms a complex with CEBPB (PubMed:19015024). Interacts with CPSF6; indicative for an association with the cleavage factor Im (CFIm) complex (By similarity). Interacts with THOC1 (PubMed:16909111). Interacts with LUZP4 (By similarity). Interacts with NCBP3 (By similarity).|||Nucleus|||Phosphorylated on tyrosine upon binding to activated CSF1R; which causes a dissociation of the two proteins. Phosphorylation on Ser-5 and/or Ser-6 is required for nuclear export. Phosphorylated on Thr-328 in insulin-stimulated adipocytes.|||Regulates the expression of myeloid transcription factors CEBPA, CEBPB and GAB2 by enhancing the levels of phosphatidylinositol 3,4,5-trisphosphate. May be involved in the differentiation of granulocytes and adipocytes. Essential for hematopoietic primitive cell survival and plays an integral role in monocytic development.|||Ubiquitously expressed, with highest levels in testis, liver and heart.|||Up-regulated following CSF1 stimulation. http://togogenome.org/gene/10090:Gm21163 ^@ http://purl.uniprot.org/uniprot/Q5FWD5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Vmn1r151 ^@ http://purl.uniprot.org/uniprot/L7N288 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Chml ^@ http://purl.uniprot.org/uniprot/A0A0R4J1A1|||http://purl.uniprot.org/uniprot/Q9QZD5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Rab GDI family.|||Cytoplasm|||Monomer. Heterotrimer composed of RABGGTA, RABGGTB and CHML; within this trimer, RABGGTA and RABGGTB form the catalytic component B, while CHML (component A) mediates Rab protein binding. Interacts with RAB1A, RAB7A and RAB27A, but has much lower affinity for RAB1A, RAB7A and RAB27A than CHM (By similarity). Interacts with the non-phosphorylated forms of RAB3A, RAB3B, RAB3C, RAB3D, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (By similarity).|||Substrate-binding subunit (component A) of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane.|||Substrate-binding subunit (component A) of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane. Less effective than CHM in supporting prenylation of Rab3 family (By similarity).|||cytosol http://togogenome.org/gene/10090:Gramd1b ^@ http://purl.uniprot.org/uniprot/Q80TI0 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ By NR1H2/LXRB and NR1H3/LXRA.|||Cell membrane|||Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (PubMed:30220461). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (PubMed:30220461). Plays a crucial role in cholesterol homeostasis in the adrenal gland and has the unique ability to localize to the PM based on the level of membrane cholesterol (PubMed:30220461). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (PubMed:30220461). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (PubMed:30220461).|||Endoplasmic reticulum membrane|||GRAM domain binds phosphatidylserine in the PM and mediates protein recruitment to endoplasmic reticulum-plasma membrane contact sites (EPCS) in response to excess cholesterol in the PM.|||Highly expressed in the adrenal gland (at protein level) and brain. Also found in the kidney, testis and macrophages.|||Mice exhibit deficiency in adrenal cholesterol ester storage and steroidogenesis.|||VASt (VAD1 Analog of StAR-related lipid transfer) domain, also known as ASTER (Greek for star) domain is a sterol-binding domain. http://togogenome.org/gene/10090:Ccng1 ^@ http://purl.uniprot.org/uniprot/P51945|||http://purl.uniprot.org/uniprot/Q5D0F7|||http://purl.uniprot.org/uniprot/Q5NC86 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family.|||Belongs to the cyclin family. Cyclin G subfamily.|||Binds to B' regulatory B subunits of protein phosphatase A (PP2A) following induction by p53 (in vitro).|||Highest levels in kidney, heart and skeletal muscle.|||May play a role in growth regulation. Is associated with G2/M phase arrest in response to DNA damage. May be an intermediate by which p53 mediates its role as an inhibitor of cellular proliferation.|||Nucleus http://togogenome.org/gene/10090:Or4f62 ^@ http://purl.uniprot.org/uniprot/Q7TQW6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or2f2 ^@ http://purl.uniprot.org/uniprot/Q7TRV8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fstl3 ^@ http://purl.uniprot.org/uniprot/Q9EQC7 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in heart, lung, kidney and testis. Continuously expressed in embryonic heart.|||Interacts with INHBA and INHBB. Interacts with FN1. Interacts with ADAM12. Interacts with MLLT10; the interaction enhances MLLT10 in vitro transcriptional activity and self-association. Interacts with MSTN (By similarity).|||Nucleus|||Secreted|||The secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiation. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. The nuclear form is probably involved in transcriptional regulation via interaction with MLLT10 (By similarity). http://togogenome.org/gene/10090:Gaa ^@ http://purl.uniprot.org/uniprot/P70699 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 31 family.|||Essential for the degradation of glycogen in lysosomes. Has highest activity on alpha-1,4-linked glycosidic linkages, but can also hydrolyze alpha-1,6-linked glucans.|||Lysosome|||Lysosome membrane http://togogenome.org/gene/10090:Lrrc59 ^@ http://purl.uniprot.org/uniprot/Q922Q8 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Can form homodimers. Interacts with SGO1. Interacts with FGF1.|||Endoplasmic reticulum membrane|||Microsome membrane|||Nucleus envelope|||Required for nuclear import of FGF1, but not that of FGF2. Might regulate nuclear import of exogenous FGF1 by facilitating interaction with the nuclear import machinery and by transporting cytosolic FGF1 to, and possibly through, the nuclear pores (By similarity). http://togogenome.org/gene/10090:H4c16 ^@ http://purl.uniprot.org/uniprot/B2RTM0|||http://purl.uniprot.org/uniprot/P62806 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.|||Belongs to the histone H4 family.|||Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.|||Chromosome|||Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:24049080). Monomethylation is performed by KMT5A/SET8 (By similarity). Trimethylation is performed by KMT5B and KMT5C and induces gene silencing (PubMed:24049080). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (By similarity).|||Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).|||Nucleus|||Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).|||Sumoylated, which is associated with transcriptional repression.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity).|||Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).|||Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. http://togogenome.org/gene/10090:Snorc ^@ http://purl.uniprot.org/uniprot/Q9CXL7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 16.5 dpc and 18.5 dpc expression is cartilage specific. In tracheal and nasal cartilage, expression is seen throughout all chondrocytes at a similar intensity while in other cartilage tissues undergoing endochondral ossification, intensity is strongest in proliferating and prehypertrophic stages. In knee epiphyseal cartilage, expression is detected from 12.5 dpc onwards, with significant up-regulation at 16.5 dpc and again at postnatal day 5. Expressed at least until 10 months of age.|||Cytoplasm|||Expressed only in cartilage, including nasal, knee epiphyseal and rib tissues (PubMed:21624478). In proliferation and hypertrophic chondrocytes, detected intracellulary and in the pericellular extracellular matrix. In primary spongiosa, detected only in the extracellular matrix (PubMed:28323137).|||In chondrocytes, induced by BMP2.|||Interacts (via the extracellular domain) with FGF2.|||Membrane|||Mutants are born with the expected Mendelian frequency and show no differences in fertility, gross morphology or body weight (PubMed:28323137). Secondary ossification centers in knee epiphyses are smaller and growth plate maturation is disturbed, but total bone length is normal. Central proliferative and hypertrophic zones are enlarged with higher extracellular matrix volume and rounded chondrocyte morphology at postnatal days P10 and P22 (PubMed:28323137).|||Plays a role in the regulation of chondrocyte maturation and postnatal endochondral ossification. May inhibit cell growth stimulation induced by FGF2.|||extracellular matrix http://togogenome.org/gene/10090:Clic4 ^@ http://purl.uniprot.org/uniprot/Q543N5|||http://purl.uniprot.org/uniprot/Q9QYB1 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the chloride channel CLIC family.|||Can insert into membranes and form poorly selective ion channels that may also transport chloride ions. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions. Promotes cell-surface expression of HRH3 (By similarity). May play a role in angiogenesis.|||Cell junction|||Cell membrane|||Cytoplasm|||Cytoplasmic vesicle membrane|||Detected in blood vessels in the retina (at protein level). Expressed to the greatest extent in vivo in heart, lung, liver, kidney, and skin.|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion (By similarity).|||Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.|||Membrane|||Mitochondrion|||Monomer. Interacts with HRH30. Interacts with AKAP9 (By similarity).|||Nucleus|||Up-regulated by calcium ions in differentiating keratinocytes.|||centrosome http://togogenome.org/gene/10090:E2f8 ^@ http://purl.uniprot.org/uniprot/Q58FA4 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene.|||Belongs to the E2F/DP family.|||Highly expressed in liver, skin, thymus and testis. Expressed in trophoblast giant cells throughout placenta development (at protein level).|||In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (By similarity).|||Induced at the onset of hepatocyte polyploidization.|||Interacts with HIF1A (By similarity). Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with E2F8. Dimerization is important for DNA-binding.|||No visible phenotype; mice develop normally and live to old age. E2f7 and E2f8 double knockout embryos die by 11.5 dpc of massive apoptosis and dilation of blood vessels and show increased expression of E2f1 and p53/Tp53, as well as many stress-related genes.|||Nucleus http://togogenome.org/gene/10090:Itih3 ^@ http://purl.uniprot.org/uniprot/Q61704 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ITIH family.|||Expressed in both liver and brain.|||Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.|||I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (HC) and one light chain, bikunin. Pre-alpha-inhibitor (P-alpha-I) is composed of ITIH3/HC3 and bikunin.|||May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.|||Secreted http://togogenome.org/gene/10090:Vmn2r8 ^@ http://purl.uniprot.org/uniprot/L7N472 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Il20 ^@ http://purl.uniprot.org/uniprot/Q2NKI0|||http://purl.uniprot.org/uniprot/Q2THG5|||http://purl.uniprot.org/uniprot/Q9JKV9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the IL-10 family.|||Forms a 1:1:1 heterotrimeric complex with its primary high-affinity heterodimeric receptor IL20RA/IL20RB.|||Immune regulatory cytokine.|||Pro-inflammatory and angiogenic cytokine mainly secreted by monocytes and skin keratinocytes that plays crucial roles in immune responses, regulation of inflammatory responses, hemopoiesis, as well as epidermal cell and keratinocyte differentiation (PubMed:23793061). Enhances tissue remodeling and wound-healing activities and restores the homeostasis of epithelial layers during infection and inflammatory responses to maintain tissue integrity. Affects multiple actin-mediated functions in activated neutrophils leading to inhibition of phagocytosis, granule exocytosis, and migration. Exert its effects via the type I IL-20 receptor complex consisting of IL20RA and IL20RB. Alternatively, can mediate its activity through a second receptor complex called type II IL-20 receptor complex composed of IL22RA1 and IL20RB (By similarity). Acts as an arteriogenic and vascular remodeling factory by activating a range of signaling processes including phosphorylations of JAK2 and STAT5 as well as activation of the serine and threonine kinases AKT and ERK1/2 (PubMed:17878297). Alternatively, can activate STAT3 phosphorylation and transcriptional activity in a JAK2, ERK1/2 and p38 MAPK-dependent manner in keratinocytes (By similarity).|||Secreted http://togogenome.org/gene/10090:Zpr1 ^@ http://purl.uniprot.org/uniprot/Q62384 ^@ Disease Annotation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a signaling molecule that communicates proliferative growth signals from the cytoplasm to the nucleus. It is involved in the positive regulation of cell cycle progression (By similarity). Plays a role for the localization and accumulation of the survival motor neuron protein SMN1 in sub-nuclear bodies, including gems and Cajal bodies. Induces neuron differentiation and stimulates axonal growth and formation of growth cone in spinal cord motor neurons. Plays a role in the splicing of cellular pre-mRNAs. May be involved in H(2)O(2)-induced neuronal cell death.|||Belongs to the ZPR1 family.|||Cajal body|||Component of an import snRNP complex composed of KPNB1, SNUPN, SMN1 and ZNF259. Interacts (via C-terminal region) with SMN1 (via C-terminal region); the interaction occurs after treatment with serum (By similarity). Interacts with elongation factor 1-alpha EEF1A1; the interaction occurs in a epidermal growth factor (EGF)-dependent manner. Interacts (via zinc fingers) with EGFR (via C-terminal cytoplasmic kinase domain); the interaction is negatively regulated in response to epidermal growth factor (EGF) stimulation and EGFR kinase activity. May also bind to the PDGFR receptor.|||Cytoplasm|||Die during early embryonic development. Embryos show growth delay, failed to form normal trophectoderm and to expand the inner cell mass.|||Expressed in brain. Expressed in the spinal cord motor neurons (at protein level). Expressed in spleen, liver, muscle, kidney and testis. Expressed in the frontal cortex, cornus ammonis, dentate gyrus of the hippocampus and in Purkinje cells of the cerebellum.|||May contribute to the severity of spinal muscular atrophy by increasing spinal motor neurons degeneration.|||Nucleus|||Up-regulated by high fat diet.|||axon|||gem|||growth cone|||nucleolus|||perinuclear region http://togogenome.org/gene/10090:Cdc16 ^@ http://purl.uniprot.org/uniprot/Q8R349 ^@ Domain|||Function|||PTM|||Sequence Caution|||Similarity|||Subunit ^@ Belongs to the APC6/CDC16 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Intron retention.|||Phosphorylated. Phosphorylation on Ser-560 occurs specifically during mitosis (By similarity).|||TPR repeats 1-7 mediate homodimerization, while the C-terminal TPR repeats bind to CDC26, burying its hydrophobic N-terminus.|||V-shaped homodimer. The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. Interacts with PPP5C and CDC20. Interacts with CDC26. Interacts with FBXO43. http://togogenome.org/gene/10090:Mycbpap ^@ http://purl.uniprot.org/uniprot/Q5SUV2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||In testis, weakly expressed in 3-week old mice and strongly expressed after expression of spermatids, especially after 10 weeks of age, during which time MYCBP/AMY-1 is also expressed.|||Interacts with MYCBP.|||May play a role in spermatogenesis. May be involved in synaptic processes (By similarity).|||Membrane http://togogenome.org/gene/10090:Zfyve21 ^@ http://purl.uniprot.org/uniprot/Q8VCM3 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasmic vesicle|||Endosome|||Interacts with PTK2/FAK1.|||Plays a role in cell adhesion, and thereby in cell motility which requires repeated formation and disassembly of focal adhesions. Regulates microtubule-induced PTK2/FAK1 dephosphorylation, an event important for focal adhesion disassembly, as well as integrin beta-1/ITGB1 cell surface expression (By similarity).|||The C-terminal region exhibits a structure similar to canonical PH domains, but lacks a positively charged interface to bind phosphatidylinositol phosphate.|||The FYVE-type zinc finger mediates interaction with PTK2/FAK1, and also interaction with PI(3)P and association with endosomes.|||Widely expressed.|||focal adhesion http://togogenome.org/gene/10090:Eif4a3l1 ^@ http://purl.uniprot.org/uniprot/E9PV04 ^@ Similarity ^@ Belongs to the DEAD box helicase family. http://togogenome.org/gene/10090:Vegfa ^@ http://purl.uniprot.org/uniprot/Q00731 ^@ Developmental Stage|||Domain|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDGF/VEGF growth factor family.|||By IL-6 and FSH in vitro.|||Cell membrane|||Contains a basic insert which acts as a cell retention signal.|||Cytoplasm|||Endoplasmic reticulum|||Golgi apparatus|||Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. Binds to the NRP1/neuropilin-1 receptor. Binding to NRP1 receptor initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (PubMed:26503042). Also binds the DEAR/FBXW7-AS1 receptor (PubMed:16293765). May play a role in increasing vascular permeability during lactation, when increased transport of molecules from the blood is required for efficient milk protein synthesis (By similarity).|||Homodimer; disulfide-linked (By similarity). Also found as heterodimer with PGF (By similarity). Interacts with NRP1 (PubMed:26503042). Interacts with isoform 2 of BSG (By similarity).|||In developing embryos, expressed mainly in the choroid plexus, paraventricular neuroepithelium, placenta and kidney glomeruli. Also found in bronchial epithelium, adrenal gland and in seminiferous tubules of testis. High expression continues in kidney glomeruli and choroid plexus in adults.|||Levels increase during pregnancy (maximum 5.5-fold at 5 days) and a more marked increase occurs during lactation (maximal 9.7-fold at 7 days). Levels decrease progressively during the phase of involution.|||Nucleus|||Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A (PubMed:35455969). Involved in protecting cells from hypoxia-mediated cell death (PubMed:35455969).|||Produced by alternative promoter usage and alternative initiation. Starts at an alternative upstream CUG codon.|||Produced by use of an alternative upstream CUG codon and post-translationally processed into the N-terminal N-VEGF form and the C-terminal secreted VEGFA form.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Or5ak22 ^@ http://purl.uniprot.org/uniprot/Q8VGC6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Jpt1 ^@ http://purl.uniprot.org/uniprot/P97825 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the JUPITER family.|||Cytoplasm|||Expressed in yolk sac, fetal brain, brain, spleen and bone marrow.|||Interacts with the complex composed, at least, of APC, CTNNB1 and GSK3B; the interaction takes place with the inactive form of GSK3B (phosphorylated at 'Ser-9').|||Modulates negatively AKT-mediated GSK3B signaling. Induces CTNNB1 'Ser-33' phosphorylation and degradation through the suppression of the inhibitory 'Ser-9' phosphorylation of GSK3B, which represses the function of the APC:CTNNB1:GSK3B complex and the interaction with CDH1/E-cadherin in adherent junctions (By similarity). Plays a role in the regulation of cell cycle and cell adhesion (PubMed:25450365). Has an inhibitory role on AR-signaling pathway through the induction of receptor proteasomal degradation (By similarity).|||Negatively regulated by the microRNA miR-132.|||Nucleus http://togogenome.org/gene/10090:Serpinb9d ^@ http://purl.uniprot.org/uniprot/Q8BMT0 ^@ Similarity ^@ Belongs to the serpin family. Ov-serpin subfamily. http://togogenome.org/gene/10090:Rab30 ^@ http://purl.uniprot.org/uniprot/Q923S9 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Cytoplasm|||Golgi apparatus|||Membrane|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). Required for maintaining the structural integrity of the Golgi apparatus, possibly by mediating interactions with cytoplasmic scaffolding proteins (By similarity).|||trans-Golgi network http://togogenome.org/gene/10090:Serinc3 ^@ http://purl.uniprot.org/uniprot/Q9QZI9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TDE1 family.|||Cell membrane|||Golgi apparatus membrane|||Highly expressed in the neuronal populations such as Purkinje cells in the cerebellum, brainstem and spinal motor neurons, locus coeruleus and raphe nuclei. Highly expressed also in thymus, kidney liver and testis.|||N-glycosylated.|||Restriction factor required to restrict infectivity of gammaretroviruses: acts by inhibiting early step of viral infection and impairing the ability of the viral particle to translocate its content to the cytoplasm. http://togogenome.org/gene/10090:Sptlc3 ^@ http://purl.uniprot.org/uniprot/Q8BG54 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.|||Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides.|||Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.|||Endoplasmic reticulum membrane|||Expressed in white and brown adipose tissues.|||SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides (By similarity). This mechanism allows to maintain ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (Probable). http://togogenome.org/gene/10090:Tomm22 ^@ http://purl.uniprot.org/uniprot/Q9CPQ3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tom22 family.|||Central receptor component of the translocase of the outer membrane of mitochondria (TOM complex) responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with the peripheral receptor TOM20 functions as the transit peptide receptor and facilitates the movement of preproteins into the translocation pore (By similarity). Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases (By similarity).|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70). Interacts with PPP2R2B and TOMM40 (By similarity).|||Mitochondrion outer membrane|||The N-terminal domain (residues 1-62) is important for binding to the unfolded mature imported proteins. Residues (49-71) of the cytoplasmic domain interacts with TOMM20 while the C-terminal segment (residues 63-82) binds presequence of preproteins. Requires the transmembrane domain (TMD), a short segment (the import sequence) in the cytoplasmic domain localizing separately from the TMD and the C-tail signal in the C-terminal domain for efficient targeting and integration into the TOM complex (By similarity). http://togogenome.org/gene/10090:Tent4a ^@ http://purl.uniprot.org/uniprot/Q6PB75 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DNA polymerase type-B-like family.|||Component of a nuclear TRAMP-like complex, an ATP-dependent exosome regulatory complex consisting of a helicase (MTREX), an oligadenylate polymerase (TENT4B or TENT4A), and a substrate specific RNA-binding factor (ZCCHC7 or ZCCHC8). Several TRAMP-like complexes exist with specific compositions and are associated with nuclear, or nucleolar RNA exosomes.|||Cytoplasm|||Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3' poly(A) tail creating a heterogeneous 3' poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation (By similarity). Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Has no terminal uridylyltransferase activity, and does not play a role in replication-dependent histone mRNA degradation via uridylation (By similarity).|||Was originally thought to have DNA polymerase activity.|||nucleoplasm http://togogenome.org/gene/10090:Foxd3 ^@ http://purl.uniprot.org/uniprot/A2BDY3|||http://purl.uniprot.org/uniprot/Q61060 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3' and acts as a transcriptional repressor (PubMed:12381664, PubMed:8798505). Also acts as a transcriptional activator (PubMed:12381664, PubMed:8798505). Negatively regulates transcription of transcriptional repressor Rhit/Zfp13 (By similarity). Promotes development of neural crest cells from neural tube progenitors (PubMed:12381664, PubMed:8798505). Restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation (PubMed:12381664, PubMed:8798505). Required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis (PubMed:12381664, PubMed:8798505).|||During early embryogenesis, not expressed in unfertilized oocytes or fertilized one-cell embryos but detected in blastocysts.|||Expressed in premigratory and migrating neural crest cells in the early embryo and in motorneuron and interneuron progenitors in the developing spinal cord.|||Interacts with POU5F1.|||Nucleus http://togogenome.org/gene/10090:Col8a2 ^@ http://purl.uniprot.org/uniprot/P25318 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ COL8A1(-)/COL8A2(-) mice exhibit decreased proliferation of mesangial cells, reduced phosphorylation of ERK1/2 and increased p27(KIP1) expression. Diabetic COL8A1(-)/COL8A2(-) mice reveal reduced mesangial expansion and cellularity and extracellular matrix expansion.|||Homotrimers, or heterotrimers in association with alpha 2(VIII) type collagens. Four homotrimers can form a tetrahedron stabilized by central interacting C-terminal NC1 trimers (By similarity).|||In the kidney, expressed in mesangial cells, glomerular endothelial cells, and tubular epithelial cells.|||Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also a component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis (By similarity).|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Proteolytically cleaved by neutrophil elastase, in vitro.|||basement membrane http://togogenome.org/gene/10090:Mup6 ^@ http://purl.uniprot.org/uniprot/A2AV72 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Lats2 ^@ http://purl.uniprot.org/uniprot/Q7TSJ6 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated and phosphorylated during M-phase and the G1/S-phase of the cell cycle. Phosphorylated and activated by STK3/MST2. Phosphorylation by NUAK2 may regulate its activity in phosphorylation and inactivation YAP1.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.|||Cytoplasm|||Expressed at high levels in ovary and testis and at lower levels in all other tissues examined.|||Interacts with and is phosphorylated by AURKA. Binds to AR (By similarity). Interacts with AJUBA during mitosis and this complex regulates organization of the spindle apparatus through recruitment of gamma-tubulin to the centrosome. Interacts (via PPxY motif) with YAP1 (via WW domains). Interacts with MOB1A and MOB1B (By similarity). Interacts with LIMD1, WTIP and AJUBA (By similarity). Interacts with SNAI1 (By similarity).|||Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ (By similarity).|||Nucleus|||centrosome|||spindle pole http://togogenome.org/gene/10090:Dync2li1 ^@ http://purl.uniprot.org/uniprot/Q8K0T2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system, facilitating the assembly of these organelles (By similarity) (PubMed:15371312). Involved in the regulation of ciliary length (By similarity).|||Belongs to the dynein light intermediate chain family.|||Cytoplasm|||Death before 11.5 dpc with defects in notochord and floor plate formation and a reduction of definitive endoderm. Mice also display anterior truncations of the forebrain, defects in the ventral body wall, in closure of the neural tube, and either an arrest of embryonic turning and heart looping or a randomization in their direction.|||Light intermediate chain of the cytoplasmic dynein complex 2, a multisubunit complex composed at least of eleven different proteins. The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the dynein-2 complex, but a subset of light chains are also shared by dynein-1 and dynein-2 complexes. Dynein-2 complex is built around two copies of cytoplasmic dynein 2 heavy chain 1 (DYNC2H1). The C-terminal region forms the motor domain, which converts the energy from ATP hydrolysis into movement. Its N-terminal region forms the tail, an extended structure that binds the other subunits and holds the two heavy chains in a homodimer. Interacts with DYNC2H1 (via N-terminus); this interaction stabilizes the dynein-2 complex structure.|||Specifically expressed by ciliated cells in brain, lung, spleen, testis and kidney (at protein level). Enriched in the ependymal layer lining the lateral ventricles (at protein level).|||Specifically expressed by monociliated cells of the ventral node from the late streak to early somite stage.|||centrosome|||cilium|||cilium axoneme|||cilium basal body http://togogenome.org/gene/10090:Fam193a ^@ http://purl.uniprot.org/uniprot/Q8CGI1 ^@ Similarity ^@ Belongs to the FAM193 family. http://togogenome.org/gene/10090:Vxn ^@ http://purl.uniprot.org/uniprot/Q8BG31 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the vexin family.|||Cell membrane|||Nucleus|||Required for neurogenesis in the neural plate and retina. Strongly cooperates with neural bHLH factors to promote neurogenesis (PubMed:29518376). http://togogenome.org/gene/10090:Sema4a ^@ http://purl.uniprot.org/uniprot/Q62178 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the semaphorin family.|||Cell membrane|||Cell surface receptor for PLXNB1, PLXNB2, PLXNB3 and PLXND1 that plays an important role in cell-cell signaling (PubMed:20043131, PubMed:17318185). Regulates glutamatergic and GABAergic synapse development (PubMed:29981480). Promotes the development of inhibitory synapses in a PLXNB1-dependent manner and promotes the development of excitatory synapses in a PLXNB2-dependent manner (PubMed:29981480). Plays a role in priming antigen-specific T-cells, promotes differentiation of Th1 T-helper cells, and thereby contributes to adaptive immunity (PubMed:15780988). Promotes phosphorylation of TIMD2 (PubMed:12374982). Inhibits angiogenesis (PubMed:17318185). Promotes axon growth cone collapse (PubMed:20043131). Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons (PubMed:20043131).|||Expressed from day 10 in the embryo. Low levels found between days 10-12. Expression peaks on day 13 with moderate levels from then until birth.|||Expressed in neurons and glia in the developing hippocampus.|||Interacts with PLXNB1, PLXNB2 and PLXNB3 (PubMed:20043131). Interacts with PLXND1 (PubMed:17318185). Interacts with TIMD2 (PubMed:12374982).|||Results are contradictory; one study (PubMed:15780988) finds no visible phenotype; mice are born at the expected Mendelian ratio and are fertile, but they present defects in T-cell differentiation and in T-cell responses to antigens. According to another publication (PubMed:15277503) gene disruption leads to degeneration of photoreceptor cells in the retina within the first month of life. http://togogenome.org/gene/10090:Ccrl2 ^@ http://purl.uniprot.org/uniprot/O35457 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By bacterial lipopolysaccharide in astrocytes.|||Cell membrane|||Expressed in macrophages, astrocytes, in glial cells. Constitutively expressed by mast cells. Detected in bronchial epithelium in OVA-induced airway inflammation. Up-regulated during dendritic cell (DC) maturation.|||It was initially reported that CCRL2 responds functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular calcium mobilization and transwell chemotaxis although no evidence for a direct ligand-receptor interaction was provided in this report (PubMed:14999816). These results are now controversial and other studies failed to confirm CCRL2 recognition and transwell chemotaxis of these chemokines or a series of other CC- and CXC-chemokines using CCRL2-transfected cells (PubMed:18794339).|||Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors.|||No visible phenotype. Deficient-mice have normal numbers of mast cells in all tissues analyzed. Wild-type and deficient mice develop marked local inflammation when sensitized with a high dose of DNP-specific IgE, however deficient mice have significantly reduced IgE-dependent passive cutaneous anaphylaxis (PCA) reactions when lower sensitizing dose is used. Deficient-mice show normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T-helper cell 2 response.|||Receptor for CCL19 and chemerin/RARRES2. Does not appear to be a signaling receptor, but may have a role in modulating chemokine-triggered immune responses by capturing and internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a functional signaling receptor. Plays a critical role for the development of Th2 responses (By similarity). http://togogenome.org/gene/10090:Xlr5a ^@ http://purl.uniprot.org/uniprot/A2BI45|||http://purl.uniprot.org/uniprot/A2BI46 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Itga9 ^@ http://purl.uniprot.org/uniprot/B8JK39|||http://purl.uniprot.org/uniprot/E9QAP0|||http://purl.uniprot.org/uniprot/Q3UT74 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin alpha chain family.|||Heterodimer of an alpha and a beta subunit. Alpha-9 (ITGA9) associates with beta-1 (ITGB1) (Probable). Integrin ITGA9:ITGB1 interacts with FBLN5 (via N-terminus) (PubMed:11805835).|||Integrin alpha-9/beta-1 (ITGA9:ITGB1) is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin.|||Membrane http://togogenome.org/gene/10090:Gipr ^@ http://purl.uniprot.org/uniprot/Q0P543 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||May form homodimers and heterodimers with GLP1R.|||N-glycosylation is required for cell surface expression and lengthens receptor half-life by preventing degradation in the ER.|||This is a receptor for GIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity). http://togogenome.org/gene/10090:Vmn1r179 ^@ http://purl.uniprot.org/uniprot/Q8R2B4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5p66 ^@ http://purl.uniprot.org/uniprot/Q8VFD2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Potential odorant receptor. http://togogenome.org/gene/10090:Mcoln3 ^@ http://purl.uniprot.org/uniprot/Q3KP78|||http://purl.uniprot.org/uniprot/Q8R4F0 ^@ Activity Regulation|||Disease Annotation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN3 sub-subfamily.|||Defects in Mcoln3 are the cause of the varitin-waddler (Va) phenotype. Classical Va mice exhibit early-onset hearing loss, vestibular defects, pigmentation abnormalities and perinatal lethality. The phenotype varitin-waddler Jackcon (Va-J), which arose in a cross segregating for Va, is similar but less severe.|||Early endosome membrane|||Endosome membrane|||Expressed in the cochlea; particularly in the inner and outer hair cells (at protein level).|||Homotetramer. Can heterooligomerize with MCOLN1; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific. May heterooligomerize with TRPV5 to form a functional distinct ion channel (By similarity). Interacts with GABARAPL2 (PubMed:24269818).|||Inhibited by lumenal H(+) and Na(+). The channel pore shows dynamic behavior and undergoes spontaneous, Ca(2+)-dependent modulation when conducting Ca(2+).|||Late endosome membrane|||Membrane|||N-glycosylated.|||No severe auditory and vestibular phenotype; does not lead to circling behavior, balance impairment or hearing loss.|||Nonselective ligand-gated cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:17989217). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (By similarity). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (PubMed:18801844). Involved in the regulation of autophagy. Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (PubMed:24269818). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events. Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (By similarity).|||The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.|||autophagosome membrane|||stereocilium membrane http://togogenome.org/gene/10090:Vmn1r34 ^@ http://purl.uniprot.org/uniprot/G3XA52 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pdgfa ^@ http://purl.uniprot.org/uniprot/G5E891|||http://purl.uniprot.org/uniprot/P20033|||http://purl.uniprot.org/uniprot/Q99L56 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the PDGF/VEGF growth factor family.|||Expression primarily localized in papillary regions with presumable expression in tubular cells comprising the loop of Henle. In the renal cortex, a widespread expression seen in the vascular smooth muscle cells and is barely detectable in interstitial cells.|||Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal lung alveolar septum formation during embryogenesis, normal development of the gastrointestinal tract, normal development of Leydig cells and spermatogenesis. Required for normal oligodendrocyte development and normal myelination in the spinal cord and cerebellum. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFB.|||Homodimer; antiparallel disulfide-linked dimer. Heterodimer with PDGFB; antiparallel disulfide-linked dimer. The PDGFA homodimer interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts with CSPG4 (By similarity).|||Lethal, due to defects in cell proliferation and migration, leading to defects in the development of the embryonic lung, gastrointestinal tract, oligodendrocytes and Leydig cells.|||Secreted|||The long form contains a basic insert which acts as a cell retention signal. http://togogenome.org/gene/10090:Ripply1 ^@ http://purl.uniprot.org/uniprot/Q2WG77 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the ripply family.|||Expressed in the anterior presomitic mesoderm and somites of stage E9.5 dpc embryos. Also expressed in tongue, diaphragm and intercostal muscles at 16.5 dpc.|||Nucleus|||Plays a role in somitogenesis. Essential for transcriptional repression of the segmental patterning genes, thus terminating the segmentation program in the presomitic mesoderm, and also required for the maintenance of rostrocaudal polarity in somites (By similarity).|||The WRPW motif is required for binding to TLE/GROUCHO proteins.|||The ripply homology domain is required for transcriptional repression. http://togogenome.org/gene/10090:Abhd11 ^@ http://purl.uniprot.org/uniprot/Q8K4F5 ^@ Induction|||Similarity|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily.|||Expressed in white adipose tissues.|||Up-regulated by rosiglitazone and down-regulated by high fat feeding. http://togogenome.org/gene/10090:Actl7a ^@ http://purl.uniprot.org/uniprot/Q9QY84 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the actin family.|||Cytoplasm|||Detected in testis. Detected at the acrosome of round spermatids (at protein level). Detected in adult and embryonic testis. Detected in developing male germ cells.|||Golgi apparatus|||Interacts (via N-terminus) with TES (via LIM domain 2). Heterodimer with TES; the heterodimer interacts with ENAH to form a heterotrimer. Interacts with ACTL9.|||May play an important role in formation and fusion of Golgi-derived vesicles during acrosome biogenesis.|||Nucleus|||acrosome|||cytoskeleton http://togogenome.org/gene/10090:Kctd5 ^@ http://purl.uniprot.org/uniprot/Q8VC57 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homopentamer (By similarity). Interacts (via C-terminus) with GRASP55/GORASP2. Interacts with CUL3 and with ubiquitinated proteins (By similarity). Interacts with CRY1 (PubMed:27123980).|||Its interaction with CUL3 suggests that it may act as a substrate adapter in some E3 ligase complex (By similarity). Does not affect the function of Kv channel Kv2.1/KCNB1, Kv1.2/KCNA2, Kv4.2/KCND2 and Kv3.4/KCNC4 (By similarity).|||Nucleus|||The BTB (POZ) domain is atypical and mediates the formation of a homopentamer instead of a homotetramer (By similarity). Homopentamerization is due to the presence of 4 residues in the BTB (POZ) domain: Leu-56, Gly-100, Val-112 and Ala-118 (By similarity).|||cytosol http://togogenome.org/gene/10090:Slc26a9 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0F7|||http://purl.uniprot.org/uniprot/Q8BU91 ^@ Activity Regulation|||Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.|||Cell membrane|||Endomembrane system|||Expressed in stomach and trachea. Abundantly expressed in the apical domain of the surface epithelial cells and the deep cells in the gastric gland. Also expressed in heart, brain, lung and liver.|||Homodimer.|||Inhibited by ammonium and thiosulfate.|||Ion transporter that can act both as an ion channel and anion exchanger (PubMed:15800055, PubMed:17120765, PubMed:31339488). Mainly acts as a chloride channel, which mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane (PubMed:31339488). Also acts as a DIDS- and thiosulfate- sensitive anion exchanger the exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15800055).|||Ion transporter that can act both as an ion channel and anion exchanger. Mainly acts as a chloride channel, which mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane. Also acts as a DIDS- and thiosulfate- sensitive anion exchanger the exchange of chloride for bicarbonate ions across the cell membrane.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Or8b3b ^@ http://purl.uniprot.org/uniprot/E9PVZ7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp13a4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0M2|||http://purl.uniprot.org/uniprot/E9QPP7|||http://purl.uniprot.org/uniprot/Q5XF90|||http://purl.uniprot.org/uniprot/S4R234 ^@ Caution|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.|||Early endosome membrane|||Expressed in brain and stomach.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Late endosome membrane|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane|||Recycling endosome membrane http://togogenome.org/gene/10090:Mtres1 ^@ http://purl.uniprot.org/uniprot/Q9CQF4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Mitochondrial RNA-binding protein involved in mitochondrial transcription regulation. Functions as a protective factor to maintain proper mitochondrial RNA level during stress. Acts at the transcription level and its protective function depends on its RNA binding ability. Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation. As heterodimer with MTRF, ejects the unfinished nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for MTRES1 and MTRF during mitoribosome rescue.|||Mitochondrion matrix|||Monomer. Interacts with POLRMT. Interacts (via S4 domain) with MTRFR (via C-terminus). Associates with mitoribosomal S39 large subunit, peptidyl tRNA and nascent chain. http://togogenome.org/gene/10090:Fam171a1 ^@ http://purl.uniprot.org/uniprot/A2ATK9|||http://purl.uniprot.org/uniprot/A2ATL0|||http://purl.uniprot.org/uniprot/A2ATL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM171 family.|||Membrane http://togogenome.org/gene/10090:Tmem176b ^@ http://purl.uniprot.org/uniprot/Q9R1Q6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TMEM176 family.|||Expressed in the developing cerebellum at constant levels from 18 dpc to P7.|||May play a role in the process of maturation of dendritic cells (By similarity). Required for the development of cerebellar granule cells.|||Mice exhibit abnormal development of the cerebellum and severe ataxia.|||Nucleus membrane|||Ubiquitously expressed with higher expression in lung, liver, kidney and colon. Expressed in cerebellar granule cells. http://togogenome.org/gene/10090:Or2ag13 ^@ http://purl.uniprot.org/uniprot/Q8VFM3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Zkscan14 ^@ http://purl.uniprot.org/uniprot/Q9Z1D9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed at high level in testis.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Cited2 ^@ http://purl.uniprot.org/uniprot/O35740 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CITED family.|||Expressed in the embryonic heart. Expressed in the ventral node, cardiac crescent and blood islands at 7.5 dpc. Expressed in the cardiac crescent, anterior lateral mesoderm and in trunk paraxial mesoderm at 8 dpc. Expressed in forebrain-midbrain boundary, branchial arches 1 and 2, heart and somites at 9.5 dpc (at protein level). Expressed in the coelomic epithelium and in cells in the underlying nephrogenic mesenchyme of the genital ridge at 10 dpc. Expressed in the genital ridge and the presumptive adrenal area at 10.5 dpc. Expressed in the gonad and in the adrenal anlagen at 12 dpc. Expressed in the cells of the adrenal cortex at 14 dpc. Expressed throughout the embryonic heart, as well as in the node and the lateral plate mesoderm (LPM), that are responsible for initiating and maintaining left-right patterning. Expressed in the crown cells of the node.|||Interacts (via C-terminus) with EP300 (via CH1 domain); the interaction is stimulated in response to hypoxia. Interacts with PPARA. Interacts (via C-terminus) with TFAP2A, TFAP2B and TFAP2C (By similarity). Interacts (via C-terminus) with SMAD2. Interacts (via C-terminus) with SMAD3 (via MH2 domain). Interacts with LHX2 (via LIM domains). Interacts with WT1 isoform 1 and isoform 3.|||Mice embryos die during gestation with left-right patterning defects and severe developmental abnormalities, including cardiac malformations, exencephaly and adrenal agenesis. Show also impaired mesonephric tubules and adrenal cortex development in embryos.|||Nucleus|||Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.|||Ubiquitous. http://togogenome.org/gene/10090:Ctag2 ^@ http://purl.uniprot.org/uniprot/Q9D9S4 ^@ Similarity ^@ Belongs to the CTAG/PCC1 family. http://togogenome.org/gene/10090:Dnaaf9 ^@ http://purl.uniprot.org/uniprot/Q7TT23 ^@ Function|||Subunit ^@ Interacts with ARL3.|||May act as an effector for ARL3. http://togogenome.org/gene/10090:Ulk2 ^@ http://purl.uniprot.org/uniprot/Q3UG39|||http://purl.uniprot.org/uniprot/Q9QY01 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated. In response to nutrient limitation, probably phosphorylated and activated by AMPK, leading to activate autophagy.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.|||Component of a complex consisting of ATG13/KIAA0652, ULK1 and RB1CC1/FIP200. Interacts (via C-terminus) with ATG13/KIAA0652. Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR (By similarity). Interacts with SYNGAP1.|||Cytoplasmic vesicle membrane|||Serine/threonine-protein kinase involved in autophagy in response to starvation.|||Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.|||The CTD-like region mediates membrane-binding and incorporation into large protein complexes.|||Widely expressed. http://togogenome.org/gene/10090:Wdr54 ^@ http://purl.uniprot.org/uniprot/Q9R0D8 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cross-linked to tightly form both dimers and trimers by TGM2. Cross-linking enhances the activation of EGF receptor-mediated signaling pathway. Cross-linking is inhibited by EGF.|||Homodimer and homotrimer; forms tight forms of dimers and trimers.|||Ubiquitinated. EGF increases ubiquitination.|||Vesicle|||WD6 repeat is required for cross-linking by TGM2.|||When cross-linked to form dimers and trimers, it has a regulatory effect on ERK signaling pathway activity in response to EGF stimulation. Colocalizes with the EGF receptor in WDR54-specific vesicle where it sustains the internalization and controls the degradation of the EGF receptor after EGF stimulation. http://togogenome.org/gene/10090:Fam229a ^@ http://purl.uniprot.org/uniprot/B2KGE5 ^@ Similarity ^@ Belongs to the FAM229 family. http://togogenome.org/gene/10090:Or6c35 ^@ http://purl.uniprot.org/uniprot/Q8VFZ8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tprkb ^@ http://purl.uniprot.org/uniprot/Q8QZZ7 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CGI121/TPRKB family.|||Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes. Interacts with TP53RK/PRPK.|||Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. TPRKB acts as an allosteric effector that regulates the t(6)A activity of the complex. TPRKB is not required for tRNA modification.|||Mouse embryos display primary microcephaly characterized by significantly shorter cortex lengths, cortex-midbrain midline lengths and cortex widths. Mice do not show a renal phenotype.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Tmem63c ^@ http://purl.uniprot.org/uniprot/Q8CBX0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as an osmosensitive calcium-permeable cation channel (PubMed:27045885). Required for the functional integrity of the kidney glomerular filtration barrier (By similarity).|||Belongs to the CSC1 (TC 1.A.17) family.|||Cell membrane http://togogenome.org/gene/10090:Tmem35a ^@ http://purl.uniprot.org/uniprot/Q9D328 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DoxX family.|||Brain (at protein level) (PubMed:27170659, PubMed:26875622, PubMed:28445721). Expressed in the spinal cord dorsal horn (at protein level) (PubMed:33422618).|||Cytoplasmic vesicle|||Endoplasmic reticulum membrane|||May interact with NGFR (By similarity). Interacts with RPN1, RPN2 and CANX (PubMed:32783947).|||Mice show a complete disruption of the assembly and function of the neuronal acetylcholine receptor (nAChR) subunit alpha-7 (CHRNA7) in the brain (PubMed:26875622, PubMed:32204458). Exhibit enhanced locomotor activity, profound abnormalities in spatial/working memory and a significant reduction of assembled nAChRs in the brain (PubMed:28445721). Display thermal hyperalgesia and mechanical allodynia accompanied by an increased number of microglia in the spinal cord dorsal horn (PubMed:33422618). Exhibit elevated basal serum corticosterone accompanied by increased anxiety-like behavior and an impairment of long-term memory (PubMed:27170659).|||Molecular chaperone which mediates the proper assembly and functional expression of the nicotinic acetylcholine receptors (nAChRs) throughout the brain (PubMed:26875622, PubMed:28445721, PubMed:32204458). Essential for the proper folding, assembly, function and surface trafficking of alpha-7 (CHRNA7), alpha-4-beta-2, alpha-3-beta-2 and alpha-3-beta-4 receptors (PubMed:26875622, PubMed:28445721, PubMed:32204458). Stably associates with ribophorin-1 (RPN1) and ribophorin-2 (RPN2) (components of the oligosaccharyl transferase (OST) complex) and with calnexin (CANX), both of which are critical for NACHO-mediated effects on CHRNA7 assembly and function (PubMed:32783947). Facilitates the proper folding and assembly of alpha-6-beta-2 and alpha-6-beta-2-beta-3 receptors and acts at early stages of the nAChRs subunit assembly (PubMed:28445721). Promotes the expression of the alpha-4(2):beta-2(3) stoichiometric form over the alpha-4(3):beta-2(2) form (By similarity).|||Peroxisome membrane http://togogenome.org/gene/10090:Tmem254 ^@ http://purl.uniprot.org/uniprot/P0DN89 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:C2cd2 ^@ http://purl.uniprot.org/uniprot/E9Q3C1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Auh ^@ http://purl.uniprot.org/uniprot/A0A0R4J023|||http://purl.uniprot.org/uniprot/Q9JLZ3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the enoyl-CoA hydratase/isomerase family.|||Catalyzes the fifth step in the leucine degradation pathway, the reversible hydration of 3-methylglutaconyl-CoA (3-MG-CoA) to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). Can catalyze the reverse reaction but at a much lower rate in vitro. HMG-CoA is then quickly degraded by another enzyme (such as HMG-CoA lyase) to give acetyl-CoA and acetoacetate. Uses other substrates such as (2E)-glutaconyl-CoA efficiently in vitro, and to a lesser extent 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA), crotonyl-CoA ((2E)-butenoyl-CoA) and 3-hydroxybutanoyl-CoA (the missing carboxylate reduces affinity to the active site) (By similarity). Originally it was identified as an RNA-binding protein as it binds to AU-rich elements (AREs) in vitro. AREs direct rapid RNA degradation and mRNA deadenylation (PubMed:10072761). Might have itaconyl-CoA hydratase activity, converting itaconyl-CoA into citramalyl-CoA in the C5-dicarboxylate catabolism pathway. The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, an antimicrobial metabolite and immunomodulator produced by macrophages during certain infections, that can act as a vitamin B12-poisoning metabolite (By similarity).|||Detected in heart, brain, liver, spleen, skeletal muscle and kidney. Expressed in brain, kidney, liver and spleen tissue (at protein level).|||Homohexamer.|||Mitochondrion http://togogenome.org/gene/10090:Adgra1 ^@ http://purl.uniprot.org/uniprot/Q6PHM3|||http://purl.uniprot.org/uniprot/Q8C4G9 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.|||Membrane|||Predominantly expressed in CNS. http://togogenome.org/gene/10090:Vps33a ^@ http://purl.uniprot.org/uniprot/Q9D2N9 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the STXBP/unc-18/SEC1 family.|||Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuole/endosome tethering (CORVET) complex. Their common core is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1 (PubMed:25266290). Interacts with RAB5C (PubMed:25266290). Interacts with UVRAG, STX17, MON1A and MON1B (By similarity). Associates with adaptor protein complex 3 (AP-3) and clathrin (By similarity). Interacts with PLEKHM1 (By similarity).|||Cytoplasmic vesicle|||Defects in Vps33a are the cause of the buff mutant which exhibits hypopigmentation in the coat and eyes, due to reduced size and number of melanosomes in their cells. In addition, mice are prone to prolonged bleeding, due to a platelet-storage pool defect.|||Early endosome|||Late endosome membrane|||Lysosome membrane|||Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS16 but not VIPAS39. The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG.|||autophagosome|||clathrin-coated vesicle http://togogenome.org/gene/10090:Acsm2 ^@ http://purl.uniprot.org/uniprot/Q8K0L3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (By similarity). Capable of activating medium-chain fatty acids (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate (By similarity).|||Mitochondrion|||Monomer. http://togogenome.org/gene/10090:Ssx2ip ^@ http://purl.uniprot.org/uniprot/A0A0R4J1A9|||http://purl.uniprot.org/uniprot/Q8VC66 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to an adhesion system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). May connect the nectin-afadin and E-cadherin-catenin system through alpha-actinin and may be involved in organization of the actin cytoskeleton at AJs through afadin and alpha-actinin (PubMed:12446711). Acts as a centrosome maturation factor, probably by maintaining the integrity of the pericentriolar material and proper microtubule nucleation at mitotic spindle poles. The function seems to implicate at least in part WRAP73; the SSX2IP:WRAP73 complex is proposed to act as regulator of spindle anchoring at the mitotic centrosome (By similarity). Involved in cell movement: localizes at the leading edge of moving cells in response to PDGF and is required for the formation of the leading edge and the promotion of cell movement, possibly via activation of Rac signaling (PubMed:22027834). Involved in ciliogenesis (By similarity). It is required for targeted recruitment of the BBSome, CEP290, RAB8, and SSTR3 to the cilia (By similarity).|||Belongs to the ADIP family.|||Interacts with SSX2 and SSX3 (By similarity). Does not interact with SSX1 and SSX4 (By similarity). Interacts with afadin and alpha-actinin (PubMed:12446711). Interacts with VAV2 (PubMed:22027834). Interacts with PCM1 (PubMed:24356449). Interacts with WRAP73 (By similarity).|||Nucleus|||Widely expressed.|||adherens junction|||centriolar satellite|||cilium basal body http://togogenome.org/gene/10090:Slc4a3 ^@ http://purl.uniprot.org/uniprot/P16283|||http://purl.uniprot.org/uniprot/Q68EG4|||http://purl.uniprot.org/uniprot/Q9ERP4 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Expressed in the brain.|||Inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS).|||Membrane|||Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane. May be involved in the regulation of intracellular pH, and the modulation of cardiac action potential (By similarity). http://togogenome.org/gene/10090:Lsm5 ^@ http://purl.uniprot.org/uniprot/P62322 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA. http://togogenome.org/gene/10090:Dok4 ^@ http://purl.uniprot.org/uniprot/Q99KE3 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ At 12.5 dpc and 13.5 dpc, expressed in the central and peripheral nervous system and in endothelia. In the nervous system, expression localized to the ventral portion of the neural tube and the dorsal root and cranial sensory ganglia. Expression confined to neurons.|||Belongs to the DOK family. Type B subfamily.|||DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK4 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway (By similarity). Putative link with downstream effectors of RET in neuronal differentiation. May be involved in the regulation of the immune response induced by T-cells (By similarity).|||Interacts with RET and TEK/TIE2. Interaction with RET is mediated through the PTB domain and requires phosphorylation of RET 'Tyr-1062'.|||PTB domain mediates receptor interaction.|||Phosphorylated on tyrosine residues in response to insulin, IGF1 or RET stimulation.|||Widely expressed. Highest levels in heart, lung and kidney. http://togogenome.org/gene/10090:Ppm1f ^@ http://purl.uniprot.org/uniprot/Q8CGA0 ^@ Cofactor|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Associates with FEM1B.|||Belongs to the PP2C family.|||Binds 2 magnesium or manganese ions per subunit.|||Dephosphorylates and concomitantly deactivates CaM-kinase II activated upon autophosphorylation, and CaM-kinases IV and I activated upon phosphorylation by CaM-kinase kinase. Promotes apoptosis (By similarity).|||Expressed in the liver. http://togogenome.org/gene/10090:Olig2 ^@ http://purl.uniprot.org/uniprot/Q9EQW6 ^@ Developmental Stage|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By SHH. Also induced by NKX6-1 in the developing spinal cord, but not in the rostral hindbrain.|||Cytoplasm|||Expressed in the ventral spinal cord as early as 9.5 dpc. Expression becomes progressively restricted to a narrow zone within the ventral neuroepithelium of the spinal cord. In the 14.5 dpc spinal cord, expressed in the oligodendrocyte progenitors of the ventral ventricular zone, but not dorsal root ganglia Schwann cells. Also expressed scattered in the mantle zone, likely corresponding to oligodendrocyte progenitors migrating out from their site of origin. In the brain, from 10.5 through 14.5 dpc, expressed in numerous cells in the ventricular and subventricular zones of the lateral and medial ganglionic eminences, suggesting that expression might not be limited to the oligodendrocytic lineage. By 15.5 dpc, dispersed throughout the gray matter, with little or no residual expression in the ventricular zone. In the postnatal brain, present preferentially in the white matter, such as corpus callosum and cerebellar medulla. Expressed in the 13.5 and 14.5 dpc retina and in the olfactory epithelium from 11.5 dpc onward.|||Expressed specifically in the brain.|||Interacts with NKX2-2 (PubMed:14573534). Interacts with ZNF488 (PubMed:16908628).|||Nucleus|||Required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain (PubMed:11955448, PubMed:12121626, PubMed:16908628). Functions together with ZNF488 to promote oligodendrocyte differentiation (PubMed:16908628). Cooperates with OLIG1 to establish the pMN domain of the embryonic neural tube (PubMed:11955448, PubMed:12121626). Antagonist of V2 interneuron and of NKX2-2-induced V3 interneuron development (PubMed:11955448, PubMed:12121626).|||The bHLH is essential for interaction with NKX2-2. http://togogenome.org/gene/10090:Tm9sf1 ^@ http://purl.uniprot.org/uniprot/Q9DBU0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.|||Lysosome membrane|||Plays an essential role in autophagy.|||autophagosome membrane http://togogenome.org/gene/10090:Gm20865 ^@ http://purl.uniprot.org/uniprot/Q62460 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Hepacam ^@ http://purl.uniprot.org/uniprot/Q640R3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer. Dimer formation occurs predominantly through cis interactions on the cell surface (By similarity). Part of a complex containing MLC1, TRPV4, AQP4 and ATP1B1 (By similarity).|||Involved in regulating cell motility and cell-matrix interactions. May inhibit cell growth through suppression of cell proliferation (By similarity).|||Membrane|||N-glycosylated.|||The cytoplasmic domain plays an important role in regulation of cell-matrix adhesion and cell motility. http://togogenome.org/gene/10090:Dusp15 ^@ http://purl.uniprot.org/uniprot/Q8R4V2 ^@ Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Cell membrane|||Down-regulated by nerve injury.|||Expression increases during oligodendrocyte differentiation. Detected in spinal cord in late fetal (18.5 dpc) and early postnatal (P3 and P7) stages. Expression decreases in later postnatal development (P14 and P30).|||Inactive. Lacks the active site.|||Isoform 1 is expressed in testis; predominantly in developing spermatocytes (at protein level) (PubMed:15138252). Isoform 2 is highly expressed in testis (PubMed:11432789). Expressed in spinal cord and specifically in oligodendroglial cells (PubMed:27532821). Expressed in embryonic brain cortex; down-regulated in mice with experimental autoimmune encephalomyelitis (EAE) (PubMed:22792334).|||May dephosphorylate MAPK13, ATF2, ERBB3, PDGFRB and SNX6 (By similarity).|||May play a role in the regulation of oligodendrocyte differentiation (PubMed:22792334). May play a role in the regulation of myelin formation (By similarity). Involved in the regulation of Erk1/2 phosphorylation in Schwann cells; the signaling may be linked to the regulation of myelination (By similarity). http://togogenome.org/gene/10090:Dapk3 ^@ http://purl.uniprot.org/uniprot/O54784|||http://purl.uniprot.org/uniprot/Q05A21 ^@ Activity Regulation|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity.|||A species-specific loss of a key phosphorylation site in murine DAPK3 seems to direct it mainly to the nucleus which is proposed to be compensated by the interaction with PAWR to maintain at least the cytoplasmic basic membrane blebbing function in the apoptosis pathway.|||Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.|||Cytoplasm|||Highly expressed in heart, brain, lung, skeletal muscle, kidney and testis. Lower levels in liver and spleen.|||Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation (By similarity). Interacts with DAXX, PAWR, ATF4, NLK, TCF7L2, UBE2D1, UBE2D2, UBE2D3, and CDC5L. Interacts with AR; enhanced by AATF.|||Nucleus|||PML body|||Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in formation of promyelocytic leukemia protein nuclear body (PML-NB). Involved in apoptosis involving PAWR which mediates cytoplasmic relocation; in vitro phosphorylates PAWR (By similarity). Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton such as in regulation of cell polarity and cell migration. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2; disrupts the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates STAT3 and enhances its transcriptional activity. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis (By similarity). Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition.|||The phosphorylation status is critical for kinase activity, oligomerization and intracellular localization. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. The phosphorylated form is localized in the cytoplasm and nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation increases the trimeric form, and its dephosphorylation favors a kinase-inactive monomeric form.|||Ubiquitinated. Ubiquitination mediated by the UBE2D3 E3 ligase does not lead to proteasomal degradation, but influences promyelocytic leukemia protein nuclear bodies (PML-NBs) formation in the nucleus.|||centromere|||centrosome http://togogenome.org/gene/10090:Nek10 ^@ http://purl.uniprot.org/uniprot/Q3UGM2 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.|||Expressed in the mammary gland, lung, spleen, and kidney.|||Interacts with RAF1 and MAP2K1; the interaction is direct with RAF1 and required for ERK1/2-signaling pathway activation in response to UV irradiation.|||Plays a role in the cellular response to UV irradiation. Mediates G2/M cell cycle arrest, MEK autoactivation and ERK1/2-signaling pathway activation in response to UV irradiation. In ciliated cells, it is involved in the regulation of mucociliary transport. http://togogenome.org/gene/10090:Sf1 ^@ http://purl.uniprot.org/uniprot/E9Q4Q2|||http://purl.uniprot.org/uniprot/Q3TZI3|||http://purl.uniprot.org/uniprot/Q3UI45 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the BBP/SF1 family.|||Necessary for the splicing of pre-mRNA. Has a role in the recognition of the branch site (5'-UACUAAC-3'), the pyrimidine tract and the 3'-splice site at the 3'-end of introns.|||Nucleus http://togogenome.org/gene/10090:Gm20815 ^@ http://purl.uniprot.org/uniprot/J3KMI0 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Chd1l ^@ http://purl.uniprot.org/uniprot/Q9CXF7 ^@ Activity Regulation|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage. Recruited to DNA damage sites through interaction with poly-ADP-ribose: specifically recognizes and binds histones that are poly-ADP-ribosylated on serine residues in response to DNA damage. Poly-ADP-ribose-binding activates the ATP-dependent chromatin remodeler activity, thereby regulating chromatin during DNA repair. Catalyzes nucleosome sliding away from DNA breaks in an ATP-dependent manner. Chromatin remodeling activity promotes PARP2 removal from chromatin.|||Adopts an inactive conformation in absence of DNA damage. Binding to poly-ADP-ribosylated histones activates the ATP-dependent chromatin remodeler activity.|||Belongs to the SNF2/RAD54 helicase family.|||Chromosome|||Interacts with nucleosomes; interacts with the acidic patch of histones. Interacts (via macro domain) with PARP1; interacts only when PARP1 is poly-ADP-ribosylated (PARylated). Interacts with CIAO1.|||Nucleus|||The macro domain mediates non-covalent poly(ADP-ribose)-binding and recruitment to DNA damage sites. Mediates auto-inhibition of ATPase activity by interacting with the N-terminal ATPase module, encompassing the helicase ATP-binding domain and helicase C-terminal domain. Binding to poly-ADP-ribosylated histones upon DNA damage releases the auto-inhibition by the macro domain and trigger ATPase activity. Does not bind monomeric ADP-ribose and mono-ADP-ribose fails to release the auto-inhibition of the ATPase module by the macro domain. http://togogenome.org/gene/10090:Wipi2 ^@ http://purl.uniprot.org/uniprot/Q80W47 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat PROPPIN family.|||Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Involved in an early step of the formation of preautophagosomal structures. Binds and is activated by phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases (PubMed:23051912, PubMed:23291478, PubMed:24954904). Mediates ER-isolation membranes contacts by interacting with the ULK1:RB1CC1 complex and PtdIns3P (By similarity). Once activated, WIPI2 recruits at phagophore assembly sites the ATG12-ATG5-ATG16L1 complex that directly controls the elongation of the nascent autophagosomal membrane.|||Interacts with TECPR1 (By similarity). Interacts with ATG16L1 (PubMed:24954904). Interacts with ATG5 (By similarity). Interacts with WIPI1 (By similarity). Interacts with WDR45 (By similarity). May interact with NUDC (By similarity). Interacts with ULK1 and RB1CC1 (By similarity).|||Preautophagosomal structure membrane|||The L/FRRG motif is required for recruitment to PtdIns3P. http://togogenome.org/gene/10090:Msx1 ^@ http://purl.uniprot.org/uniprot/P13297 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a transcriptional repressor (PubMed:7823952, PubMed:22629437, PubMed:23371388). Capable of transcription autoinactivation (PubMed:10215616). Binds to the consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory elements (DARE) in the gene promoter, thereby repressing the transcription of CGA/alpha-GSU and GNRHR (PubMed:23371388). Represses transcription of myoblast differentiation factors (PubMed:16600910, PubMed:22629437). Binds to core enhancer regions in target gene promoters of myoblast differentiation factors with binding specificity facilitated by interaction with PIAS1 (PubMed:16600910). Recruits histone H3 methyltransferases such as EHMT2/G9a to gene promoter regions which leads to inhibition of myoblast differentiation via transcriptional repression of differentiation factors (PubMed:22629437). Regulates, in a stage-specific manner, a developmental program of gene expression in the fetal tooth bud that controls odontoblast differentiation and proliferation of dental mesenchymal cells (PubMed:7914451, PubMed:8898217, PubMed:24028588, PubMed:27713059, PubMed:29148101). At the bud stage, required for mesenchymal molar tooth bud development via facilitating reciprocal signaling between dental epithelial and mesenchymal cells (PubMed:8898217). May also regulate expression of Wnt antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme (PubMed:27713059). Required for BMP4 expression in dental mesenchyme cells (PubMed:8898217). Also, in response to BMP4, required for BMP4 expression in neighboring dental epithelial cells (PubMed:8898217). Required for maximal FGF4-induced expression of SDC1 in dental mesenchyme cells (PubMed:8898217). Also in response to SDC1, required for SDC1 expression in neighboring dental epithelial cells (PubMed:8898217). At the early bell stage, acts to drive proliferation of dental mesenchyme cells, however during the late bell stage acts as an homeostatic regulator of the cell cycle (PubMed:24028588, PubMed:29148101). Regulates proliferation and inhibits premature mesenchymal odontogenesis during the bell stage via inhibition of the Wnt signaling component CTNNB1 and subsequent repression of the odontoblast differentiation factors BMP2, BMP4, LEF1, ALPL and BGLAP/OCN (PubMed:24028588, PubMed:29148101). Additionally, required for correct development and fusion of the palatal shelves and embryonic mandibular formation (PubMed:7914451). Plays a role in embryonic bone formation of the middle ear, skull and nasal bones (PubMed:7914451). Required for correct formation and thickness of the nail plate (PubMed:11369996). May play a role in limb-pattern formation (PubMed:1677742).|||Belongs to the Msh homeobox family.|||Expressed in the developing limb bud at 11.5 dpc (at protein level) (PubMed:22629437). Expressed in the pituitary gland at 11.5 dpc, reaching peak abundance at 13.5 dpc with abundance decreasing from 15.5 dpc onwards (PubMed:23371388). Expression is most prevalent in the ventral pituitary area where developing gonadotropes reside (PubMed:23371388). Expressed in early bell stage and mid bell stage in dental mesenchymal cells at 15.5 and 17.5 dpc respectively (at protein level) (PubMed:24028588, PubMed:29148101). Expressed in the mesenchyme subjacent to the thickened epithelium of the nail bed at 16.5 and 18.5 dpc (at protein level) (PubMed:11369996).|||Interacts with CREBBP/CBP, TBP and SP1; interaction with these transcription activators may inhibit autoinactivation (PubMed:10215616). Interacts (via homeobox domain) with EHMT2/G9a (PubMed:22629437). Interacts with EHMT1/GLP (PubMed:22629437). Interacts (via C-terminus) with PIAS1 (via N-terminus); the interaction is required for the localization of both proteins to the nuclear periphery and specific binding of MSX1 to the core enhancer region in target gene promoters (PubMed:16600910). Interacts with H1-5 (PubMed:16600910).|||It is uncertain whether Met-1 or Met-7 is the initiator.|||Knockout mice die shortly after birth (PubMed:7914451). Development of mesenchymal molar tooth buds is arrested at the bud stage, as a result of reduced expression of Bmp4 and Lef1 in the dental mesenchyme at 13.5 and 14.5 dpc, there is no change in expression in the dental epithelium (PubMed:8898217, PubMed:27713059). Decrease in the expression of the Wnt signaling gene Tcf7, and an increase in Dkk2, Sfrp1 and Sfrp2 in the mandibular molar tooth mesenchyme at 13.5 dpc (PubMed:27713059). Expression of Dkk2 and Sfrp2 expands into the distal tooth mesenchyme in mandibular molar tooth buds at 13.5 dpc (PubMed:27713059). Decrease in Sdc1 expression in the dental mesenchyme at 13.5 dpc (PubMed:8898217). Palatal shelves are correctly elevated however not fused with each other or with the nasal septum at 14.75 dpc (PubMed:7914451). Reduced nail bed thickness with pitting defects and irregular shape at 18.5 dpc (PubMed:11369996). Complete cleft of the secondary palate at birth, including loss of both the maxillary shelf and palatine shelf (PubMed:7914451). Absence of bone development in the premaxilla along with absent upper incisors and alveolar process (PubMed:7914451). Absence of mandibular alveolar process and incisor tooth buds, foreshortening of the distal tooth-bearing mandible, a slightly reduced overall mandibular length, and an abnormal lower border and anterior segment (PubMed:7914451). Newborn mice show retarded first and second molar teeth at the tooth bud stage with a significant reduction in the amount of condensed dental follicle and papilla mesenchyme (PubMed:7914451). The nasal bones appear more rectangular, parietal bones show a slight overlap, there is a deficiency of the medial portions of the frontal bones which results in an enlarged anterior fontanelle and sutural bone (PubMed:7914451). Failure to form of the processus brevis of the malleus with an overall reduction in height of the malleus in the middle ear (PubMed:7914451).|||Nucleus|||Sumoylated by PIAS1, desumoylated by SENP1 (PubMed:16678795). Sumoylation of Lys-15 and Lys-133 not required for interaction with H1-5, transcriptional repression, inhibition of myoblast differentiation, or binding to gene promoters (PubMed:16600910). http://togogenome.org/gene/10090:Mup1 ^@ http://purl.uniprot.org/uniprot/A2CEL0|||http://purl.uniprot.org/uniprot/A2CEL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Gm20747 ^@ http://purl.uniprot.org/uniprot/Q5FWB5 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Cryzl1 ^@ http://purl.uniprot.org/uniprot/Q921W4 ^@ Similarity ^@ Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily. http://togogenome.org/gene/10090:Cdkn2aipnl ^@ http://purl.uniprot.org/uniprot/Q9D211 ^@ Similarity|||Subunit ^@ Belongs to the CARF family.|||Interacts with XRN2; the interaction is direct. http://togogenome.org/gene/10090:Calca ^@ http://purl.uniprot.org/uniprot/P70160|||http://purl.uniprot.org/uniprot/Q3V1A7|||http://purl.uniprot.org/uniprot/Q99JA0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the calcitonin family.|||CGRP induces vasodilation. It dilates a variety of vessels including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role. It also elevates platelet cAMP (By similarity).|||Causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.|||Detected in nerve cells of cerebrum, hippocampus and pons/midbrain in newborns, and only in nerve cells of pons/midbrain in adult.|||Secreted http://togogenome.org/gene/10090:2210016L21Rik ^@ http://purl.uniprot.org/uniprot/A0A0R4J099|||http://purl.uniprot.org/uniprot/Q3UY34 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CUSTOS family.|||Nucleus envelope|||Plays a role in the regulation of Wnt signaling pathway during early development. http://togogenome.org/gene/10090:Slco4a1 ^@ http://purl.uniprot.org/uniprot/Q8K078 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ A conserved histidine residue in the third TMD (His-190) may play an essential role in the pH sensitivity of SLCO4A1/OATP4A1-mediated substrate transport.|||Belongs to the organo anion transporter (TC 2.A.60) family.|||Cell membrane|||Organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormones 3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4) and 3,3',5'-triiodo-L-thyronine (rT3), conjugated steroids such as estrone 3-sulfate and estradiol 17-beta glucuronide, bile acids such as taurocholate and prostanoids such as prostaglandin E2, likely operating in a tissue-specific manner (By similarity). May be involved in uptake of metabolites from the circulation into organs such as kidney, liver or placenta. Possibly drives the selective transport of thyroid hormones and estrogens coupled to an outward glutamate gradient across the microvillous membrane of the placenta (By similarity). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable). http://togogenome.org/gene/10090:Fer1l5 ^@ http://purl.uniprot.org/uniprot/P0DM40 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ferlin family.|||Cell membrane|||Expressed in differentiating myoblasts and myotubes.|||Interacts (via second C2 domain) with EHD1 and EHD2.|||Membrane|||Plays a role in myoblast fusion; probable mediator of endocytic recycling for membrane trafficking events during myotube formation.|||Up-regulated during myotube formation. http://togogenome.org/gene/10090:Gm20877 ^@ http://purl.uniprot.org/uniprot/J3QPZ4 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Tmod2 ^@ http://purl.uniprot.org/uniprot/Q9JKK7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tropomodulin family.|||Binds to the N-terminus of tropomyosin and to actin.|||Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton (By similarity).|||Neuronal-tissue specific.|||cytoskeleton http://togogenome.org/gene/10090:Gje1 ^@ http://purl.uniprot.org/uniprot/Q9CX92 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A connexon is composed of a hexamer of connexins.|||Belongs to the connexin family. Beta-type (group I) subfamily.|||Cell membrane|||Expressed at the posterior region of the lens vesicle at embryonic stage 11.5 dpc. Detected at the tip of elongating lens fiber cells at stage 12.5 dpc. Expressed in lens epithelial cells, and weakly in retina, at stage 15.5 dpc.|||Highly expressed in lens, where it is mainly found in lens fibers and to a lesser extent in lens epithelium (PubMed:18385072, PubMed:18849090). Weakly expressed in retina (PubMed:18849090). Not detected in other tissues tested (PubMed:18385072, PubMed:18849090).|||Mediates calcium-independent ATP release, suggesting activity as a hemichannel (PubMed:18849090). Does not form functional gap junctions (PubMed:18849090). May play a non-essential role in eye lens development (PubMed:18385072, PubMed:27038752).|||No visible phenotype. Eye morphology appears to be normal with no significant effects on lens transparency and refraction. Expression levels of the connexins Cx46 and Cx50 in lens tissue are slightly reduced. http://togogenome.org/gene/10090:Pdcd10 ^@ http://purl.uniprot.org/uniprot/Q8VE70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PDCD10 family.|||Cell membrane|||Cytoplasm|||Golgi apparatus membrane|||Homodimer. Interacts (via C-terminus) with CCM2. Interacts (via C-terminus) with PXN. Interacts (via N-terminus) with STK25. Interacts (via N-terminus) with STK26. Interacts (via N-terminus) with STK24. Interacts with GOLGA2. Identified in a complex with KRIT1 and CCM2. Interacts with KDR/VEGFR2 (By similarity). Interaction with KDR/VEGFR2 is enhanced by stimulation with VEGFA (PubMed:20371769). Interacts with RIPOR1 (via C-terminus); this interaction is required for the association of RIPOR1 with either STK24 and STK26 kinases and occurs in a Rho-independent manner (By similarity).|||Lethal at an early embryonic stage due to defects in angiogenesis, vasculogenesis and hematopoiesis. Mice exhibit low levels of KDR/VEGFR2.|||Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and STK26 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex (By similarity). Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development (By similarity). http://togogenome.org/gene/10090:Gtdc1 ^@ http://purl.uniprot.org/uniprot/Q8BW56 ^@ Similarity ^@ Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily. http://togogenome.org/gene/10090:Eif5a2 ^@ http://purl.uniprot.org/uniprot/Q8BGY2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-5A family.|||Binds to 80S ribosomes. Actively translating ribosomes show mutually exclusive binding of eIF5a (EIF5A or EIF5A2) and EEF2/eEF2 (By similarity). Interacts with DAPL1; interaction takes place at the polypeptide exit tunnel of hibernating ribosomes and prevents translation (By similarity).|||Cytoplasm|||Endoplasmic reticulum membrane|||Lys-50 undergoes hypusination, a unique post-translational modification that consists in the addition of a butylamino group from spermidine to lysine side chain and leads to the formation of a hypusine residue. eIF-5As are the only known proteins to undergo this modification, which is essential for their function.|||Nucleus|||Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts (By similarity). Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step (By similarity). Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity (By similarity). http://togogenome.org/gene/10090:Pik3c3 ^@ http://purl.uniprot.org/uniprot/Q6PF93 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PI3/PI4-kinase family.|||Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. As part of PI3KC3-C1, promotes endoplasmic reticulum membrane curvature formation prior to vesicle budding. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity).|||Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth regulatory subunit in a mutually exclusive manner are: the PI3K complex I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2) containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex (By similarity). Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:17589504). PI3KC3-C1 probably associates with PIK3CB (PubMed:21059846). Interacts with RAB7A in the presence of PIK3R4 (By similarity). Interacts with AMBRA1 (PubMed:17589504). Interacts with BECN1P1/BECN2 (By similarity). Interacts with SLAMF1 (PubMed:22493499). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts with NCKAP1L (By similarity). Interacts with ATG14; this interaction is increased in the absence of TMEM39A (By similarity). Interacts with STEEP1; the interaction is STING1-dependent and required for trafficking of STING1 from the endoplasmic reticulum (By similarity). Interacts with YWHAG (By similarity).|||Late endosome|||Midbody|||Ubiquitinated via 'Lys-29'- and 'Lys-48'-linked ubiquitination by UBE3C, promoting its degradation. Deubiquitination by ZRANB1/TRABID promotes its stabilization, leading to autophagosome maturation.|||autophagosome http://togogenome.org/gene/10090:Mcm7 ^@ http://purl.uniprot.org/uniprot/Q3U4T8|||http://purl.uniprot.org/uniprot/Q61881 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (By similarity). Uncomplexed form does not show ATPase or DNA helicase (PubMed:12207017). Required for S-phase checkpoint activation upon UV-induced damage (By similarity).|||Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.|||Belongs to the MCM family.|||Chromosome|||Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex. Interacts with the ATR-ATRIP complex and with RAD17. Interacts with TIPIN. Interacts with MCMBP. Interacts with ANKRD17. Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR.|||Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.|||Nucleus|||O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.|||Ubiquitinated by ECS(LRR1) E3 ubiquitin-protein ligase complex when forks converge following formation of DNA interstrand cross-links (PubMed:33590678). During mitosis, ubiquitinated by TRAIP when forks converge following formation of DNA interstrand cross-links (PubMed:33590678). Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3 (By similarity). If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase (PubMed:33590678). http://togogenome.org/gene/10090:Tlr6 ^@ http://purl.uniprot.org/uniprot/Q3UV88|||http://purl.uniprot.org/uniprot/Q9EPW9 ^@ Caution|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Animals with a double knockout of APOE and TLR6, fed a Western diet for 12 weeks, have less aortic plaque formation than single APOE knockout mice. They also show lower serum concentrations of IL1A, ILB and IL18.|||Belongs to the Toll-like receptor family.|||Cell membrane|||Detected in thymus, spleen, ovary and lung. Expressed in macrohpages.|||Golgi apparatus|||Homodimer (via cytoplasmic TIR domain) (By similarity). Heterodimer with TLR2 via their respective extracellular domains (PubMed:19931471). Binds MYD88 via their respective TIR domains (Probable). Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR4. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4:TLR6 heterodimerization and signal initiation (By similarity). The heterodimer TLR2:TLR6 interacts with CD14 and CD36 in response to triacylated lipopeptides (By similarity).|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||Membrane|||Membrane raft|||Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides (PubMed:19931471). In response to diacylated lipopeptides, forms the activation cluster TLR2:TLR6:CD14:CD36, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR2. In complex with TLR4, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion (PubMed:20037584, PubMed:23812099).|||phagosome membrane http://togogenome.org/gene/10090:Pipox ^@ http://purl.uniprot.org/uniprot/Q3UEJ8|||http://purl.uniprot.org/uniprot/Q9D826 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MSOX/MTOX family.|||Binds 1 FAD per subunit.|||Kidney and liver.|||Metabolizes sarcosine, L-pipecolic acid and L-proline.|||Monomer.|||Peroxisome http://togogenome.org/gene/10090:Paqr3 ^@ http://purl.uniprot.org/uniprot/Q0VAZ2|||http://purl.uniprot.org/uniprot/Q6TCG8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ADIPOR family.|||Functions as a spatial regulator of RAF1 kinase by sequestrating it to the Golgi.|||Golgi apparatus membrane|||Membrane http://togogenome.org/gene/10090:Has1 ^@ http://purl.uniprot.org/uniprot/Q61647 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the NodC/HAS family.|||Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction. Also able to catalyze the synthesis of chito-oligosaccharide depending on the substrate.|||Membrane http://togogenome.org/gene/10090:Gdf1 ^@ http://purl.uniprot.org/uniprot/A2RT05|||http://purl.uniprot.org/uniprot/P20863|||http://purl.uniprot.org/uniprot/Q3TRG1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Expressed almost exclusively in the nervous system.|||Homodimer; disulfide-linked.|||May mediate cell differentiation events during embryonic development.|||Membrane|||Secreted|||This protein is produced by a bicistronic gene which also produces the CERS1 protein from a non-overlapping reading frame. http://togogenome.org/gene/10090:Sntg1 ^@ http://purl.uniprot.org/uniprot/Q8BNW6|||http://purl.uniprot.org/uniprot/Q8C415|||http://purl.uniprot.org/uniprot/Q925E1 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Adapter protein that binds to and probably organizes the subcellular localization of a variety of proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex. May participate in regulating the subcellular location of diacylglycerol kinase-zeta to ensure that diacylglycerol is rapidly inactivated following receptor activation (By similarity).|||Belongs to the syntrophin family.|||Interacts with the dystrophin protein DMD and related proteins DTNA and DTNB. Interacts with DGKZ (By similarity).|||Nucleus|||The PDZ domain binds to the last three or four amino acids of DGKZ. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity).|||cytoskeleton http://togogenome.org/gene/10090:Hnrnpdl ^@ http://purl.uniprot.org/uniprot/D3YTQ3 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Def6 ^@ http://purl.uniprot.org/uniprot/Q8C2K1 ^@ Disease Annotation|||Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Cytoplasm|||Defects in Def6 results in spontaneous development of a lupus-like syndrome in aging female mice. It is characterized by the accumulation of effector/memory T-cells and IgG B-cells, profound hypergammaglobulinemia, autoantibody production, and glomerulonephritis.|||Interacts with IRF4, activated RAC1 and F-actin. Both the phosphorylated and non-phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) (By similarity). Interacts with ZAP70. Interacts with RAB11A (By similarity).|||Nucleus|||Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42 (PubMed:12648457, PubMed:12923183). Can regulate cell morphology in cooperation with activated RAC1 (PubMed:12648457, PubMed:12923183). Involved in immune homeostasis by ensuring proper trafficking and availability of T-cell regulator CTLA-4 at T-cell surface (By similarity). Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling. Required for optimal T-cell effector function, lymphocyte homeostasis and the prevention of systemic autoimmunity (By similarity).|||The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding.|||Thymus.|||Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response to T-cell activation.|||Up-regulated in differentiating Th2 cells and down-regulated in Th1 cells.|||cytoskeleton|||filopodium|||perinuclear region http://togogenome.org/gene/10090:Cxcr1 ^@ http://purl.uniprot.org/uniprot/Q810W6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Interacts with IL8. Interacts with GNAI2.|||Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. http://togogenome.org/gene/10090:Btbd3 ^@ http://purl.uniprot.org/uniprot/P58545 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a key regulator of dendritic field orientation during development of sensory cortex. Also directs dendrites toward active axon terminals when ectopically expressed.|||In the somatosensory cortex, specifically expressed in spiny stellate neurons during barrel formation. Also expressed in the olfactory bulb, piriform cortex and hippocampus.|||Not expressed in early postnatal somatosensory cortex at postnatal day 1 (P1): weakly expressed at P2, coincident with innervation by thalamocortical axons into layer IV cortex, followed by a barrel-like expression pattern established over the next few days.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Rnf8 ^@ http://purl.uniprot.org/uniprot/Q8VC56 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ (Microbial infection) May interact with the L.monocytogenes protein actA; however, given these errors in the sequence (AJ242721), the relevance of the interaction with actA remains to be confirmed.|||According to a well-established model, RNF8 initiate H2A 'Lys-63'-linked ubiquitination leading to recruitment of RNF168 to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidence is however required to confirm these data.|||Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin. 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger.|||Belongs to the RNF8 family.|||Cytoplasm|||E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis (PubMed:20153262, PubMed:28552346). At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.|||Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2. Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N. Interacts with RXRA. Interacts (via FHA domain) with ATM-phosphorylated MDC1. Interacts (via FHA domain) with 'Thr-4829' phosphorylated HERC2 (via C-terminus) (By similarity). Interacts with PIWIL1; leading to sequester RNF8 in the cytoplasm (PubMed:28552346). Interacts with WRAP53/TCAB1 (By similarity).|||Male mice are infertile, while females do not show defects. Male mice display defects in histone H2A and H2B ubiquitination in testis cells. While meiotic sex chromosome inactivation in the XY body prior to meiosis is not affected, H4K16ac is decreased, leading to defects in the replacement of histones by protamines during spermiogenesis. Mice lacking both Rnf8 and Chfr develop thymic lymphomas and chromosomes are frequently altered, due to defects in DNA damage response and defects in damage-induced activation of ATM kinase.|||Midbody|||Nucleus|||The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and phosphorylated HERC2 (By similarity). This domain is also required for proper recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent (By similarity).|||The precise role of Rnf8 at telomeres is subject to debate. 2 publications reported recruitment of Rnf8 at uncapped telomeres followed by regulation of non-homologous end joining (NHEJ), however the 2 publications reported different data and conclusions. According to a report, Rnf8 promotes telomere end protection and inhibits NHEJ by mediating ubiquitination via 'Lys-63'-linked ubiquitin and stabilization of Tpp1 at uncapped telomeres (PubMed:22101936). According to another report, Rnf8 recruitment at uncapped telomeres leads to promote NHEJ and the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that Rnf8 may have a detrimental role in case of telomeric crisis and enhance cancer development by aggravating telomere-induced genome instability (PubMed:21857671).|||telomere http://togogenome.org/gene/10090:Ap5b1 ^@ http://purl.uniprot.org/uniprot/Q3TAP4 ^@ Function|||Subunit ^@ As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.|||Probably part of the adaptor protein complex 5 (AP-5), a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1. Interacts with ZFYVE26 and SPG11 (By similarity). http://togogenome.org/gene/10090:Rps5 ^@ http://purl.uniprot.org/uniprot/P97461 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS7 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Agxt2 ^@ http://purl.uniprot.org/uniprot/B7ZP16|||http://purl.uniprot.org/uniprot/H7BWY3|||http://purl.uniprot.org/uniprot/Q3UEG6 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.|||Can metabolize asymmetric dimethylarginine (ADMA) via transamination to alpha-keto-delta-(NN-dimethylguanidino) valeric acid (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) synthase, and this activity provides mechanism through which the kidney regulates blood pressure.|||Homotetramer.|||Knockout mice are hypertensive.|||Mitochondrion http://togogenome.org/gene/10090:Agbl2 ^@ http://purl.uniprot.org/uniprot/Q8CDK2 ^@ Activity Regulation|||Caution|||Cofactor|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AGBL2 and AGBL3 double mutants are viable and display no obvious phenotypic alterations.|||Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Inhibited by RARRES1.|||Interacts with RARRES1, KIF11 and MAPRE1.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins (PubMed:25103237). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein (PubMed:25103237). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:25103237). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK (PubMed:25103237).|||Up-regulated during ciliogenesis.|||Was initially shown to catalyze the removal of carboxy-terminus tyrosine from alpha-tubulin (By similarity). However, later studies did not identified any detyrosinase or deglycylase activities from the carboxy-terminus of tubulin (PubMed:25103237).|||Was originally thought to have detyrosinating activity from C-terminal positions on tubulin.|||Widely expressed. Expressed in tissues with motile cilia such as testis, lung and trachea. Also detected in brain, eye, muscle, pancreas, intestine, stomach, pituitary, spleen, adrenal and kidney. Expressed in mitral and granular cells in brain.|||centriole|||cilium basal body|||cytosol http://togogenome.org/gene/10090:Rab27a ^@ http://purl.uniprot.org/uniprot/Q544U7|||http://purl.uniprot.org/uniprot/Q9ERI2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rab family.|||Binds SYTL1, SYTL2, SLAC2B, MYRIP, SYTL3, SYTL4, SYTL5 and MLPH. Interacts with UNC13D. Interacts with RPH3A and RPH3A. Does not interact with the BLOC-3 complex (heterodimer of HPS1 and HPS4) (By similarity). Interacts (GDP-bound form preferentially) with DENND10 (By similarity).|||Detected in melanocytes. Expressed abundantly in the stomach and is predominantly localized at the apical region of gastric-surface mucus cells. Also expressed in the thymus and lung.|||Endosome|||Late endosome|||Lysosome|||Melanosome|||Membrane|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Activated by GEFs such as DENND10.|||Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion. Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. http://togogenome.org/gene/10090:Slc5a3 ^@ http://purl.uniprot.org/uniprot/Q3UMR9|||http://purl.uniprot.org/uniprot/Q9JKZ2 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Functions as a retroviral receptor for M813 murine leukemia virus (MuLV) entry.|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.|||Cell membrane|||Electrogenic Na(+)-coupled sugar symporter that actively transports myo-inositol and its stereoisomer scyllo-inositol across the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1 (By similarity). Maintains myo-inositol concentration gradient that defines cell volume and fluid balance during osmotic stress, in particular in the fetoplacental unit and central nervous system (PubMed:12582158, PubMed:24595108). Forms coregulatory complexes with voltage-gated K(+) ion channels, allosterically altering ion selectivity, voltage dependence and gating kinetics of the channel. In turn, K(+) efflux through the channel forms a local electrical gradient that modulates electrogenic Na(+)-coupled myo-inositol influx through the transporter (PubMed:24595108) (By similarity). Associates with KCNQ1-KCNE2 channel in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (PubMed:24595108). Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (By similarity). Provides myo-inositol precursor for biosynthesis of phosphoinositides such as PI(4,5)P2, thus indirectly affecting the activity of phosphoinositide-dependent ion channels and Ca(2+) signaling upon osmotic stress (By similarity).|||Expressed in placenta at 14.5 dpc.|||Highly expressed in kidney, placenta, and brain and at a lesser extent in thymus, lung, bladder, and testes (PubMed:12582158). Expressed in the choroid plexus epithelium (at protein level) (PubMed:24595108).|||Interacts with KCNQ2 (via the pore module) (By similarity). Interacts with KCNQ1; this interaction is direct (PubMed:24595108). Forms coregulatory complexes with ion channels KCNQ2-KCNQ3 and KCNQ1-KCNE2 (PubMed:24595108) (By similarity).|||Membrane|||Mutant embryos show brain myo-inositol deficiency and central apnea and die soon after birth due to hypoventilation. http://togogenome.org/gene/10090:Gm20825 ^@ http://purl.uniprot.org/uniprot/J3QM67 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Rbm4b ^@ http://purl.uniprot.org/uniprot/Q8VE92 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accumulates according to a circadian rhythm in the SCN.|||Expressed in the suprachiasmatic nucleus (SCN) (at protein level). Expressed in the suprachiasmatic nucleus (SCN).|||Interacts with TNPO3, which may mediate nuclear import of the protein.|||Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA.|||nucleolus http://togogenome.org/gene/10090:Fam83h ^@ http://purl.uniprot.org/uniprot/Q148V8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM83 family.|||Expressed in tooth follicle, eye, liver and kidney.|||Interacts with CSNK1A1; recruits CSNK1A1 to keratin filaments. Interacts with KRT18 and probably other keratins.|||May play a major role in the structural organization and calcification of developing enamel. May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration.|||cytoskeleton http://togogenome.org/gene/10090:Gpr62 ^@ http://purl.uniprot.org/uniprot/Q80UC6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice show any abnormality in growth and behavior. Both male and female are fertile.|||Endosome membrane|||Expressed in the brain and testes. Expressed widely, in the brain, including the cerebral cortex, cerebellum, hippocampus,thalamus and pituitary gland. In the testes, expressed specifically in the germ cells.|||Expression in the testes starts 25 days after birth and continues thereafter.|||Homodimer (PubMed:28912303). Forms heterodimer with MTNR1B (By similarity). Interacts with ARRB1 and ARRB2 in a spontaneous and agonist-independent manner; leading to the internalization of GPR62 in the endosomal compartment (By similarity).|||Lacks the conserved DRY and BBXXB motifs. The restoration of these motifs affects its constitutive activity.|||Orphan G-protein coupled receptor. Constitutively activates the G(q/11)/inositol phosphate and the G(s)-alpha/cAMP signaling pathways (PubMed:28912303). Has spontaneous activity for beta-arrestin recruitment (By similarity). Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization (By similarity). http://togogenome.org/gene/10090:Dock1 ^@ http://purl.uniprot.org/uniprot/Q8BUR4 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the DOCK family.|||Cytoplasm|||Interacts with the SH3 domains of CRK and NCK2 via multiple sites. Interacts with nucleotide-free RAC1 via its DOCKER domain. Interacts with ELMO1, ELMO2 and probably ELMO3 via its SH3 domain. Interacts with RAC1 (By similarity). Interacts with ELMO1 and ADGRB1 (PubMed:17960134). Identified in a complex with AUTS2 and ELMO2 (PubMed:25533347).|||Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1.|||Membrane|||The DOCKER domain is necessary and sufficient for the GEF activity. http://togogenome.org/gene/10090:Ints10 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0V1|||http://purl.uniprot.org/uniprot/E9Q360|||http://purl.uniprot.org/uniprot/Q8K2A7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Integrator subunit 10 family.|||Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. Interacts with POLR2A.|||Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes. May be not involved in the recruitment of cytoplasmic dynein to the nuclear envelope by different components of the INT complex.|||Nucleus http://togogenome.org/gene/10090:Gbgt1 ^@ http://purl.uniprot.org/uniprot/Q8VI38 ^@ Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 6 family.|||Binds 1 Mn(2+) ion per subunit.|||Catalyzes the formation of Forssman glycolipid via the addition of N-acetylgalactosamine (GalNAc) in alpha-1,3-linkage to GalNAcb-1,3Gala-1,4Galb-1,4GlcCer (Gb4Cer) (PubMed:14573676). Forssman glycolipid (also called Forssman antigen; FG) probably serves for adherence of some pathogens (PubMed:14573676). Conversely, it diminishes Shiga toxins susceptibility (PubMed:14573676).|||Golgi apparatus membrane|||The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis (By similarity). http://togogenome.org/gene/10090:Vmn1r36 ^@ http://purl.uniprot.org/uniprot/Q8R2E3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptges2 ^@ http://purl.uniprot.org/uniprot/Q8BWM0 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily.|||Constitutively expressed. Not induced during tissue inflammation. Down-regulated in the absence of PTGES.|||Cytoplasm|||Deficient mice displays no obvious phenotype and are fertile. Loss of PTGES2 expression does not result in a measurable decrease in PGE2 levels in any tissue or cell type examined from healthy mice (PubMed:19010439). Injection of the diabetogenic agent streptozotocin (STZ) at a dose to induce type-1 diabetes to knockout (KO) mice aggravates STZ-induced liver toxicity associated with high lethality, despite similar glucose levels (PubMed:25076362).|||Golgi apparatus membrane|||Homodimer. Interacts with EXOSC10 (By similarity). May interact with CEBPB.|||Isomerase activity is increased by sulfhydril compounds. Dithiothreitol (DTT) is most effective, followed by glutathione (GSH) and 2-mercaptoethanol.|||Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro). The biological function and the GSH-dependent property of PTGES2 is still under debate (By similarity). In vivo, PTGES2 could form a complex with GSH and heme and would not participate in PGE2 synthesis but would catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA) (By similarity). May also have transactivation activity toward IFN-gamma (IFNG), possibly via an interaction with CEBPB; however, the relevance of transcription activation activity remains unclear (PubMed:12050152).|||It is not known if heme and GST are required for prostaglandin synthase activity. The protein copurifies with heme and GST when DTT is omitted during the purification procedure. The GSH-heme complex-bound enzyme has been proposed to act as a lyase and catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA). Boiling the enzyme leads to loss of prostaglandin synthase activity, but does not eliminate the lyase activity. Besides, free heme can catalyze the formation of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) (By similarity). A more recent study demonstrates the GSH-dependent property of PTGES2, DTT dissociates the bound heme to produce active PGE2 synthase in vitro (By similarity). PTGES2 can only catalyzes PGE2 synthesis in the free state as an enzyme, while in vivo it forms a complex with heme and does not participate in PGE2 synthesis (By similarity). In agreement with this study, the in vivo evidence from PTGES2 deficient mice do not show that this protein is responsible for the PGE2 production under basal or pathophysiological conditions (PubMed:19010439).|||Nucleus|||Synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme.|||Widely expressed. Expressed in brain, heart, liver, colon and lung. http://togogenome.org/gene/10090:Septin6 ^@ http://purl.uniprot.org/uniprot/Q9R1T4 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.|||Cleavage furrow|||Coordinated expression with SEPT2 and SEPT7.|||Cytoplasm|||Expressed in the cerebral cortex (at protein level) (PubMed:20181826). Associated with synaptic vesicles in various brain regions, including glomeruli of the olfactory bulb (at protein level) (PubMed:11064363).|||Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Involved in cytokinesis. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (By similarity).|||Midbody|||Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Filaments are assembled from asymmetrical heterotrimers, composed of SEPTIN2, SEPTIN6 and SEPTIN7 that associate head-to-head to form a hexameric unit. Within the trimer, directly interacts with SEPTIN2 and SEPTIN7. Also interacts with SEPTIN9 and SEPTIN12. Interaction with SEPTIN12 alters filament structure. Component of a septin core octameric complex consisting of SEPTIN12, SEPTIN7, SEPTIN6 and SEPTIN2 or SEPTIN4 in the order 12-7-6-2-2-6-7-12 or 12-7-6-4-4-6-7-12 and located in the sperm annulus. Interacts with SOCS7. Interacts with HNRNPA1 (By similarity).|||flagellum|||kinetochore|||spindle http://togogenome.org/gene/10090:Slmap ^@ http://purl.uniprot.org/uniprot/Q3URD3 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SLMAP family.|||Expressed in atrial and ventricular chambers of the primitive heart at 9 dpc. Expressed in somites at 11 dpc. Expressed in atrial and ventricular chambers and interventricular and interatrial septum at 13 dpc. Expressed in myotubes between 13 and 15 dpc. Expressed in skeletal muscles at 18 dpc.|||Expressed in proliferating myoblasts and differentiated myotubes (at protein level). Expressed in myoblasts, cardiac and skeletal muscles.|||Homodimer. Interacts with myosin.|||M line|||May play a role during myoblast fusion.|||Z line|||centrosome|||sarcolemma http://togogenome.org/gene/10090:Or1e33 ^@ http://purl.uniprot.org/uniprot/Q8VGR6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Paqr6 ^@ http://purl.uniprot.org/uniprot/D3Z1S5|||http://purl.uniprot.org/uniprot/Q0VBT6|||http://purl.uniprot.org/uniprot/Q6TCG5 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the ADIPOR family.|||Cell membrane|||Homodimer.|||Membrane|||Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).|||Plasma membrane progesterone (P4) receptor coupled to G proteins. Seems to act through a G(s) mediated pathway. Involved in neurosteroid inhibition of apoptosis. May be involved in regulating rapid P4 signaling in the nervous system. Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone. http://togogenome.org/gene/10090:Angptl2 ^@ http://purl.uniprot.org/uniprot/Q9R045 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Induces sprouting in endothelial cells through an autocrine and paracrine action.|||Secreted|||Widely expressed in heart, tongue, lung and skeletal muscle. Also found in lower levels in kidney, epididymis and testis. http://togogenome.org/gene/10090:Kcnk15 ^@ http://purl.uniprot.org/uniprot/B2RVL1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Membrane http://togogenome.org/gene/10090:Siah3 ^@ http://purl.uniprot.org/uniprot/B2RWG3 ^@ Domain|||Function|||Similarity ^@ Belongs to the SINA (Seven in absentia) family.|||E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.|||The RING-type zinc finger domain is essential for ubiquitin ligase activity.|||The SBD domain (substrate-binding domain) mediates the interaction with substrate proteins. It is related to the TRAF family. http://togogenome.org/gene/10090:Pef1 ^@ http://purl.uniprot.org/uniprot/Q8BFY6 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ COPII-coated vesicle membrane|||Calcium-binding protein that acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium. Together with PDCD6, acts as calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in endoplasmic reticulum (ER)-Golgi transport by regulating the size of COPII coats. In response to cytosolic calcium increase, the heterodimer formed with PDCD6 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification. Its role in the heterodimer formed with PDCD6 is however unclear: some evidence shows that PEF1 and PDCD6 work together and promote association between PDCD6 and SEC31 in presence of calcium. Other reports show that PEF1 dissociates from PDCD6 in presence of calcium, and may act as a negative regulator of PDCD6 (By similarity). Also acts as a negative regulator of ER-Golgi transport; possibly by inhibiting interaction between PDCD6 and SEC31 (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||Heterodimer; heterodimerizes (via the EF-hand 5) with PDCD6. Dissociates from PDCD6 in presence of calcium.|||Membrane|||Ubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Efemp2 ^@ http://purl.uniprot.org/uniprot/G5E8D6|||http://purl.uniprot.org/uniprot/Q542X5|||http://purl.uniprot.org/uniprot/Q9WVJ9 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Aneurysm may be prevent with postnatal administration of ACE inhibitor and/or angiotensin II receptor blocker (ARB).|||At E(15), found in the perichondrium of the developing bone. At E(14) detected in the lung parenchyma.|||Belongs to the fibulin family.|||Cleaved by ELANE; produces a 50-55 kDa fragment. Cleaved by MMP2 and MMP9; produces several fragments.|||Expressed in elastic fibers of the skin, near the dermal-epidermal junction, surrounding the hair follicles and throughout the dermis (PubMed:26178373). Expressed in tendon around tenocytes (PubMed:26711913). Prominently expressed in cartilage, bone, perichondrium and ligaments. Also detected in bone marrow stroma (PubMed:26690653). Expressed in aorta, lung, and esophagus (PubMed:17324935).|||Homodimer; disulfide-linked (By similarity). Multimer; allows heparin binding (By similarity). Monomer (PubMed:17324935). Binds preferentially to p53 mutants (PubMed:10380882). Interacts with FBN1 (via N-terminal domain); this interaction inhibits EFEMP2 binding to LOX and ELN (By similarity). Interacts with ELN with moderate affinity; this interaction regulates ELN self-assembly maturation stage (PubMed:16478991, PubMed:17324935). Interacts with PCOLCE (PubMed:26220971). Interacts with collagen type IV trimer (COL4A1-COL4A1-COL4A2), NID2 and moderately with COL15A1-derived endostatin (PubMed:17324935). Interacts with EMILIN1; this interaction promotes the incorporation of EFEMP2 into the extracellular matrix (PubMed:28717224). Interacts with LTBP4; the LTBP4 long form (LTBP4L) has a stronger binding affinity than the LTBP4 short form and the LTBP4 long form promotes fibrillar deposition of EFEMP2 (PubMed:25713297). Interacts with LOX (via propeptide); this interaction is strong and facilitates formation of ternary complexes with ELN during elastic fiber assembly; this interaction limits interaction of EFEMP2 with FBLN5 (By similarity). Interacts with PITX2 (By similarity). Interacts with FBLN5 with moderate affinity (By similarity). Interacts with LOXL1 (via propeptide), LTBP1 and TGFB1 stronger than with LOXL2 and LTBP3 (By similarity).|||Homozygous mice for the EFEMP2 gene appear to be outwardly normal (PubMed:16478991, PubMed:28508064). Homozygous mice exhibit severe lung and vascular defects including emphysema, artery tortuosity, irregularity, aneurysm, rupture, and resulting hemorrhages (PubMed:16478991, PubMed:19855011, PubMed:26178373, PubMed:28508064). Mice died perinatally (PubMed:16478991, PubMed:19855011). Mice with conditional knockout of EFEMP2, in vascular smooth muscle, grow normally, are fertile and exhibit an arterial stiffness (PubMed:19855011). Mice with conditional knockout of EFEMP2, in endothelial cell (EC) are healthy with an normal aorta (PubMed:20019329). Mice with conditional knockout of EFEMP2, in smooth muscle cells, die spontaneously at approximately 2 months of age despite absence of embryonic or neonatal lethality. Aortae exhibit large aneurysms exclusively in the ascending aorta. Aneurysms are observed with complete penetrance (PubMed:20019329, PubMed:26486174, PubMed:23636094, PubMed:26220971). Homozygous mice for the EFEMP2 gene die within 1-2 days after birth. Embryos at 19 dpc show bilateral forelimb contractures (PubMed:26711913, PubMed:26690653). Newborn homozygous mice demonstrate normal morphology of the skeleton (PubMed:26690653).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated; contains mostly complex-type glycans. Not O-glycosylated.|||Plays a crucial role in elastic fiber formation in tissue, and in the formation of ultrastructural connections between elastic laminae and smooth muscle cells in the aorta, therefore participates in terminal differentiation and maturation of smooth muscle cell (SMC) and in the mechanical properties and wall integrity maintenance of the aorta (PubMed:16478991, PubMed:19855011, PubMed:20019329, PubMed:26486174, PubMed:26711913, PubMed:28508064). In addition, is involved in the control of collagen fibril assembly in tissue throught proteolytic activation of LOX leading to cross- linking of collagen and elastin (PubMed:26690653, PubMed:26711913, PubMed:26220971, PubMed:26178373). Also promotes ELN coacervation and participates in the deposition of ELN coacervates on to microfibrils but also regulates ELN cross- linking through LOX interaction (PubMed:17324935). Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling (PubMed:23636094).|||basement membrane|||extracellular matrix http://togogenome.org/gene/10090:Gabre ^@ http://purl.uniprot.org/uniprot/A2AMW3 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ligand-gated ion channel (TC 1.A.9) family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Postsynaptic cell membrane|||Synaptic cell membrane http://togogenome.org/gene/10090:Rasal1 ^@ http://purl.uniprot.org/uniprot/Q9Z268 ^@ Function ^@ Probable inhibitory regulator of the Ras-cyclic AMP pathway. Plays a role in dendrite formation by melanocytes. http://togogenome.org/gene/10090:Lad1 ^@ http://purl.uniprot.org/uniprot/P57016 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Anchoring filament protein which is a component of the basement membrane zone.|||Expressed in kidney, lung and keratinocytes followed by liver, spleen and brain. Not expressed in testis, skeletal and heart muscle and in fibroblasts.|||basement membrane http://togogenome.org/gene/10090:Xlr5b ^@ http://purl.uniprot.org/uniprot/A2BI50 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Gpatch1 ^@ http://purl.uniprot.org/uniprot/Q9DBM1 ^@ Similarity ^@ Belongs to the GPATCH1 family. http://togogenome.org/gene/10090:Lmcd1 ^@ http://purl.uniprot.org/uniprot/Q8VEE1 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc expressed in the myocardium and forming anterior foregut epithelium. By 12.5 dpc, expression is observed in the airways of the developing lung as well as in the myocardium. At 14.5 dpc, when proximal-distal differentiation in the lung is proceeding rapidly, expression is observed at high levels in the distal but not proximal airways of the developing lung. By 16.5 dpc, expression decreases in airway epithelium in the lung and expression is also observed in the vascular smooth muscle of pulmonary arteries (at protein level).|||Cytoplasm|||Expressed in distal airway epithelium of the lung, vascular smooth muscle, and myocardium.|||Interacts with beta-dystroglycan (By similarity). Interacts with GATA1, GATA4 and GATA6.|||Mice display a marked increase in cardiac hypertrophy.|||Nucleus|||The LIM zinc-binding domains and the Cys-rich region mediate interaction with GATA6.|||Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue-specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter. Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway. http://togogenome.org/gene/10090:Eif2b4 ^@ http://purl.uniprot.org/uniprot/Q61749 ^@ Function|||Similarity|||Subunit ^@ Belongs to the eIF-2B alpha/beta/delta subunits family.|||Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.|||Complex of five different subunits; alpha, beta, gamma, delta and epsilon. http://togogenome.org/gene/10090:Tshz3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J017|||http://purl.uniprot.org/uniprot/Q8CGV9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the teashirt C2H2-type zinc-finger protein family.|||Expressed in branchio and viscero motoneurons at 10.5 dpc. Expressed in the nucleus ambiguus (nA) motoneurons at 15.5 dpc. Expressed in the brainstem respiratory rhythm generator (RRG), including two interacting neuronal networks constituting two oscillators: the pre-Boetzinger complex (preBoetC) at 15.5 dpc and the embryonic parafacial respiratory group (e-pF or pFRG) at 14.4 dpc, that contributes both to motor coordination of the respiratory apparatus and confers central chemosensitivity, as well as in cranial motoneurons targeting chest muscles that control the upper airway opening. Expressed in the developing urinary tract. Expressed in ureteric bud (UB) stalk at 11.5 dpc. Expressed in mesenchymal cells along and around the UB stalk, and absent from the UB epithelium and in scattered cells within the metanephric medullary stroma at 12.5 dpc. Expressed in mesenchymal cells in proximal ureters at 14 dpc, preceding the smooth muscle precursor cells differentiation and the expression of contractile proteins from 15 dpc. Expressed in mesenchymal cells of the ureter and renal pelvis, and in renal medullary stroma, in the mesenchymal cells adjacent to the epithelium and in the peripheral mesenchyme where smooth muscle (SM) starts to differentiate; the outer rim of nephrogenic mesenchyme was negative at 15.5. In the bladder, expressed in the submucosal loose connective tissue adjacent to the epithelium and in the detrusor SM layer at 18.5 dpc.|||Expressed in corticostriatal neurons.|||Interacts (via N-terminus) with HDAC1 and HDAC2; the interaction is direct. Found in a trimeric complex with APBB1 and HDAC1; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (By similarity). Interacts (via homeobox domain) with APBB1 (via PID domain 1).|||Mice fail to breathe and die at birth. Display pronounced cell death of motoneurons in the nucleus ambiguus and induce strong alterations of rhythmogenesis in the embryonic parafacial respiratory group (e-pF or pFRG) oscillator and cranial motoneurons that control the upper airways. Mice also fail to form small smooth cells in the proximal ureter and urine flow is impaired because of functional obstruction caused by absent peristalsis in the proximal ureter that leads to hydronephrosis and hydroureter phenotypes.|||Nucleus|||Transcriptional regulator involved in developmental processes. Functions in association with APBB1, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. TSHZ3-mediated transcription repression involves the recruitment of histone deacetylases HDAC1 and HDAC2. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s). Regulates the development of neurons involved in both respiratory rhythm and airflow control. Promotes maintenance of nucleus ambiguus (nA) motoneurons, which govern upper airway function, and establishes a respiratory rhythm generator (RRG) activity compatible with survival at birth. Involved in the differentiation of the proximal uretic smooth muscle cells during developmental processes. Involved in the up-regulation of myocardin, that directs the expression of smooth muscle cells in the proximal ureter. Involved in the modulation of glutamatergic synaptic transmission and long-term synaptic potentiation (PubMed:27668656).|||Up-regulated by BMP4.|||growth cone http://togogenome.org/gene/10090:Bub1 ^@ http://purl.uniprot.org/uniprot/O08901 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated when the cells enters mitosis.|||BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.|||Early embryonic lethality.|||Highly expressed in testis. Weakly expressed in spleen and lung.|||Interacts with BUB3 and KNL1. Interacts (when phosphorylated) with PLK1. The BUB1-BUB3 complex interacts with MAD1L1 (By similarity).|||Nucleus|||Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (By similarity). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. Essential during early and later stages of embryonic development. Necessary for postimplantation embryogenesis and proliferation of primary embryonic fibroblasts and plays an important role in spermatogenesis and fertility.|||The KEN box is required for its ubiquitination and degradation.|||Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1.|||Upon spindle-assembly checkpoint activation it is hyperphosphorylated and its kinase activity toward CDC20 is stimulated. Phosphorylation at Thr-595 is required for interaction with PLK1, phosphorylation at this site probably creates a binding site for the POLO-box domain of PLK1, thus enhancing the PLK1-BUB1 interaction (By similarity).|||kinetochore http://togogenome.org/gene/10090:Ttc39d ^@ http://purl.uniprot.org/uniprot/Q0VF76 ^@ Similarity ^@ Belongs to the TTC39 family. http://togogenome.org/gene/10090:H1f5 ^@ http://purl.uniprot.org/uniprot/P43276 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H1/H5 family.|||Chromosome|||Citrullination at Arg-54 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.|||H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter.|||Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Interacts with MSX1.|||Nucleus|||The C-terminal domain is required for high-affinity binding to chromatin. http://togogenome.org/gene/10090:Rassf10 ^@ http://purl.uniprot.org/uniprot/Q8BL43 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation|||Tissue Specificity ^@ Aberrant splicing.|||Expressed in neural progenitor cells (at protein level).|||Expression increases from 10 dpc to 12 dpc and gradually decreases after 15 dpc (at protein level).|||Plays an important role in regulating embryonic neurogenesis.|||centrosome|||cytosol|||spindle pole http://togogenome.org/gene/10090:Myo9a ^@ http://purl.uniprot.org/uniprot/D3Z3A8|||http://purl.uniprot.org/uniprot/Q8C170 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.|||Cytoplasm|||Detected in whole embryos at 7, 11, 15 and 17 dpc. Also present in limb buds from 13.5 dpc. At 16.5 dpc, it is expressed throughout the developing nervous system, eye, inner ear, kidney, thyroid gland and teeth.|||Expressed in the eye, lung, liver, brain, heart, kidney, skeletal muscle and spleen. No detection was found in liver. In the brain, expressed in the ependymal cells of the third ventricle and the aqueduct (PubMed:19828736).|||Knockout mice display retarded growth, a dome-shaped skull, and develop severe hydrocephalus with stenosis and closure of the ventral caudal third ventricle and the aqueduct.|||Membrane|||Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Regulates Rho by stimulating it's GTPase activity in neurons. Required for the regulation of neurite branching and motor neuron axon guidance (PubMed:27259756).|||Phosphorylated by ALPK1 following monosodium urate monohydrate (MSU)-induced inflammation.|||Represents an unconventional myosin. This protein should not be confused with the conventional myosin-9 (MYH9).|||Synapse|||growth cone http://togogenome.org/gene/10090:Romo1 ^@ http://purl.uniprot.org/uniprot/P60603 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the MGR2 family.|||Detected in brain, liver and kidney.|||Has antibacterial activity against a variety of bacteria including S.aureus, P.aeruginosa and M.tuberculosis. Acts by inducing bacterial membrane breakage (By similarity).|||Induces production of reactive oxygen species (ROS) which are necessary for cell proliferation. May play a role in inducing oxidative DNA damage and replicative senescence. May play a role in the coordination of mitochondrial morphology and cell proliferation (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Or7g34 ^@ http://purl.uniprot.org/uniprot/Q8VFF1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcbd2 ^@ http://purl.uniprot.org/uniprot/Q9CZL5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the pterin-4-alpha-carbinolamine dehydratase family.|||Homotetramer. Interacts with DYRK1B (By similarity).|||Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2 (By similarity).|||Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity. http://togogenome.org/gene/10090:Dtx3 ^@ http://purl.uniprot.org/uniprot/E9Q3J1|||http://purl.uniprot.org/uniprot/Q80V91 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Deltex family.|||Cytoplasm|||Homodimer. May form a heterodimer with other members of the Deltex family. Interacts with NOTCH1.|||In the CNS, it is expressed in the developing neural tube starting from 10.5 dpc in the spinal cord and around 11.5 dpc in the telencephalon. Expressed ubiquitously throughout the spinal cord and telencephalon during neurogenesis. Expressed throughout the developing retina at 15.5 dpc. Not expressed in the somite or presomite during somitogenesis. Expressed slightly later that Dtx2.|||Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity.|||Strongly expressed in testis and brain. Weakly expressed in kidney. http://togogenome.org/gene/10090:Klhdc9 ^@ http://purl.uniprot.org/uniprot/Q3USL1 ^@ Subunit ^@ Interacts with CCNA1. http://togogenome.org/gene/10090:Rhobtb1 ^@ http://purl.uniprot.org/uniprot/Q9DAK3 ^@ Similarity|||Tissue Specificity ^@ Belongs to the small GTPase superfamily. Rho family.|||Highest expression in heart and testis. http://togogenome.org/gene/10090:Abcg1 ^@ http://purl.uniprot.org/uniprot/Q0VDW9|||http://purl.uniprot.org/uniprot/Q64343 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.|||Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta-hydroxycholesterol and this transport is coupled to hydrolysis of ATP (PubMed:14668945). The lipid efflux is ALB-dependent. Is an active component of the macrophage lipid export complex. Could also be involved in intracellular lipid transport processes. The role in cellular lipid homeostasis may not be limited to macrophages. Prevents cell death by transporting cytotoxic 7beta-hydroxycholesterol (By similarity).|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed mainly in brain, thymus, lung, adrenals, spleen and placenta. Little or no expression in liver, kidney, heart, muscle or testes.|||Golgi apparatus membrane|||Homodimer; disulfide-linked. Homooligomer. May form heterodimers with several heterologous partners of the ABCG subfamily. Forms heterodimers with ABCG4. Interacts with CAV1; this interaction regulates ABCG1-mediated cholesterol efflux.|||Membrane|||Palmitoylation at Cys-315 seems important for trafficking from the endoplasmic reticulum.|||Strongly induced in macrophage cell line RAW 264.7 during cholesterol influx. Induction is mediated by the liver X receptor/retinoid X receptor (LXR/RXR) pathway. Down-regulated by endotoxins or cytokines (TNF and IL1) in J-774 macrophages.|||The cholesterol efflux is enhanced by APOA1. http://togogenome.org/gene/10090:Aprt ^@ http://purl.uniprot.org/uniprot/P08030 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the purine/pyrimidine phosphoribosyltransferase family.|||Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Cables1 ^@ http://purl.uniprot.org/uniprot/Q9ESJ1 ^@ Caution|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cyclin family.|||Cyclin-dependent kinase binding protein. Enhances cyclin-dependent kinase tyrosine phosphorylation by nonreceptor tyrosine kinases, such as that of CDK5 by activated ABL1, which leads to increased CDK5 activity and is critical for neuronal development, and that of CDK2 by WEE1, which leads to decreased CDK2 activity and growth inhibition. Positively affects neuronal outgrowth. Plays a role as a regulator for p53/p73-induced cell death (By similarity).|||Cytoplasm|||Expressed in embryo at 15 dpc and strongly expressed in postmitotic neurons of the subplate, cortical plate, subventrical and marginal zones at 18 dpc (at protein level). Expressed in embryo at 7 dpc onwards.|||Found in a complex with p53/TP53 (By similarity). Found in a number of complexes with CDK2, CDK3, CDK5, ABL1, TDRD7, CDK17, CCNA1, CCNE1 and TP73. Interacts with CDK2, CDK3, CDK5, ABL1 and TDRD7.|||Nucleus|||Phosphorylated on Ser-274 by CCNE1/CDK3. Phosphorylated on serine/threonine residues by CDK5 and on tyrosine residues by ABL1. Also phosphorylated in vitro by CCNA1/CDK2, CCNE1/CDK2, CCNA1/CDK3 and CCNE1/CDK3.|||PubMed:10896159 demonstrated that CABLES1 is not associated with CDK3.|||Ubiquitous. Expressed in postnatal day 1 (P1), in postmitotic neurons of the subplate, cortex (V/VI) and marginal zone; in postnatal day 7 (P7), in all layers of the cerebral cortex and in the CA1 and CA2 regions of the hippocampus (at protein level). Highly expressed in brain, kidney, liver and lung.|||growth cone http://togogenome.org/gene/10090:Slc4a11 ^@ http://purl.uniprot.org/uniprot/A2AJN7 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Belongs to the anion exchanger (TC 2.A.31) family.|||Cell membrane|||Expressed in the endothelial cells of the cornea. In the inner ear, is located in fibrocytes underlying the stria vascularis. In the kidney, is expressed in the thin descending limb of Henle loop.|||Glycosylated.|||Homodimer.|||Multifunctional transporter with an impact in cell morphology and differentiation (PubMed:20185830). In the presence of borate B(OH)4(-), acts as a voltage-dependent electrogenic Na(+)-coupled B(OH)4(-) cotransporter controlling boron homeostasis (By similarity). At early stages of stem cell differentiation, participates in synergy with ITGA5-ITGB1 and ITGAV-ITGB3 integrins and BMPR1A to promote cell adhesion and contractility that drives differentiation toward osteogenic commitment while inhibiting adipogenesis (PubMed:33247189). In the absence of B(OH)4(-), acts as a Na(+)-coupled OH(-) or H(+) permeable channel with implications in cellular redox balance. Regulates the oxidative stress response in corneal endothelium by enhancing antioxidant defenses and protecting cells from reactive oxygen species. In response to hypo-osmotic challenge, also acts as water permeable channel at the basolateral cell membrane of corneal endothelial cells and facilitates transendothelial fluid reabsorption in the aqueous humor. In the presence of ammonia, acts as an electrogenic NH3/H(+) cotransporter and may play a role in ammonia transport and reabsorption in renal Henle's loop epithelium (By similarity).|||Mutant mice show corneal defects characterized by progressive thickening of the stroma and descement membrane concomitant with increased sodium chloride concentration in the stroma (PubMed:20185830, PubMed:23813972). They show impaired urinary concentration, increased urinary volume, and increased urinary sodium loss in the kidney. They also show stress-induced morphological changes of fibrocytes of the inner ear resulting in deafness. http://togogenome.org/gene/10090:Uroc1 ^@ http://purl.uniprot.org/uniprot/Q3UEL5|||http://purl.uniprot.org/uniprot/Q8VC12 ^@ Similarity ^@ Belongs to the urocanase family. http://togogenome.org/gene/10090:Wdr48 ^@ http://purl.uniprot.org/uniprot/Q8BH57 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat WDR48 family.|||Cytoplasm|||Interacts with USP46. Interacts with USP1. Interacts with USP12. Component of the USP12-WDR20-WDR48 deubiquitinating complex. Interacts with PHLPP1. Interacts with RAD51AP1; the interaction is direct and promotes formation of a trimeric complex with RAD51 via RAD51AP1. Interacts with ATAD5; the interaction regulates USP1-mediated PCNA deubiquitination. Interacts with RAD51; the interaction is enhanced under replication stress.|||Late endosome|||Lysosome|||Nucleus|||Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46. Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate. Also activates deubiquitinating activity of complexes containing USP12. Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme. Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination. Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes.Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress.|||The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46. http://togogenome.org/gene/10090:Smug1 ^@ http://purl.uniprot.org/uniprot/Q6P5C5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the uracil-DNA glycosylase (UDG) superfamily. SMUG1 family.|||Nucleus|||Recognizes base lesions in the genome and initiates base excision DNA repair. Acts as a monofunctional DNA glycosylase specific for uracil (U) residues in DNA with a preference for single-stranded DNA substrates. The activity is greater toward mismatches (U/G) compared to matches (U/A). Excises uracil (U), 5-formyluracil (fU) and uracil derivatives bearing an oxidized group at C5 [5-hydroxyuracil (hoU) and 5-hydroxymethyluracil (hmU)] in ssDNA and dsDNA, but not analogous cytosine derivatives (5-hydroxycytosine and 5-formylcytosine), nor other oxidized bases. The activity is damage-specific and salt-dependent. The substrate preference is the following: ssDNA > dsDNA (G pair) = dsDNA (A pair) at low salt concentration, and dsDNA (G pair) > dsDNA (A pair) > ssDNA at high salt concentration. http://togogenome.org/gene/10090:Lamtor1 ^@ http://purl.uniprot.org/uniprot/Q9CQ22 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 6.5 dpc expressed throughout the embryo with relative abundance in the visceral endoderm.|||Belongs to the LAMTOR1 family.|||Embryos die at egg cylinder stage due to growth retardation, associated with altered endosomes and lysosomes organizations and impaired membrane protein transport in the visceral endoderm.|||Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:19177150, PubMed:29158492, PubMed:30020076). Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane (PubMed:19177150, PubMed:29158492, PubMed:30020076). Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated (PubMed:19177150). LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane (PubMed:19177150). LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes (By similarity). Also involved in the control of embryonic stem cells differentiation via non-canonical RagC/RRAGC and RagD/RRAGD activation: together with FLCN, it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (PubMed:30595499). Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes (By similarity). May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes (By similarity). May also play a role in RHOA activation (By similarity).|||Late endosome membrane|||Lysosome membrane|||N-terminal myristoylation and palmitoylation mediates its recruitment to lysosome membranes, thereby promoting localization of the Ragulator complex to lysosomes. N-myristoylation by NMT1 is required for palmitoylation at Cys-3 and Cys-4.|||Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 (By similarity). LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer (By similarity). Interacts with LAMTOR2 and LAMTOR3; the interaction is direct (PubMed:19177150). The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD; regulated by amino acid availability (By similarity). The Ragulator complex interacts with SLC38A9; the probable amino acid sensor (By similarity). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Associates with the lysosomal V-ATPase complex; interaction promotes the guanine nucleotide exchange factor (GEF) of the Ragulator complex (By similarity). Interacts with MMP14 (By similarity). Interacts with CDKN1B; prevents the interaction of CDKN1B with RHOA leaving RHOA in a form accessible to activation by ARHGEF2 (By similarity). Interacts with PIP4P1 (PubMed:29644770).|||Ubiquitinated at Lys-60, Lys-103 and Lys-104 by UBE3A in neurons, promoting its degradation by the proteasome, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (PubMed:30020076). Ubiquitination at Lys-20 impairs the association with the lysosomal V-ATPase complex. Deubiquitination at Lys-20 by USP32 promotes the association with the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (By similarity). http://togogenome.org/gene/10090:C2cd2l ^@ http://purl.uniprot.org/uniprot/Q80X80 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Endoplasmic reticulum membrane|||Homodimer.|||Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (By similarity). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (By similarity). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (By similarity). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (By similarity). Positively regulates insulin secretion in response to glucose (PubMed:24012759). Phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (By similarity).|||Phosphorylation at the C-terminus acidifies the protein and leads to disassociation from the acidic cell membrane. Reassociates with the cell membrane upon dephosphorylation.|||The SMP-LBD domain is a lipid transport module, which binds glycerolipids with a preference for phosphatidylinositol (PI). http://togogenome.org/gene/10090:Ly6a ^@ http://purl.uniprot.org/uniprot/P05533 ^@ Function|||PTM|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Not phosphorylated.|||O-glycosylated. Not N-glycosylated.|||T-cell activation.|||Widely expressed. http://togogenome.org/gene/10090:Dnm1l ^@ http://purl.uniprot.org/uniprot/E9PUD2|||http://purl.uniprot.org/uniprot/Q8K1M6 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.|||Endomembrane system|||Expressed in the cerebellum and in several regions of the cerebrum and diencephalon. Strongly expressed in the cerebellar Purkinje cells and in the pontile giant neurons.|||Functions in mitochondrial and peroxisomal division (PubMed:19578372, PubMed:19752021, PubMed:22564413, PubMed:23283981, PubMed:24508339, PubMed:29478834, PubMed:32484300). Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism (PubMed:24508339). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:24508339). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:24508339). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (By similarity). Required for formation of endocytic vesicles (By similarity). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (PubMed:19752021, PubMed:22564413). Required for normal brain development, including that of cerebellum (PubMed:19578372, PubMed:22564413). Facilitates developmentally regulated apoptosis during neural tube formation (PubMed:19578372). Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues (PubMed:19578372). Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (By similarity). Required for programmed necrosis execution (By similarity). Rhythmic control of its activity following phosphorylation at Ser-643 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834).|||Golgi apparatus|||Homotetramer; dimerizes through the N-terminal GTP-middle region of one molecule binding to the GED domain of another DNM1L molecule. Oligomerizes in a GTP-dependent manner to form membrane-associated tubules with a spiral pattern. Interacts with GSK3B and MARCHF5. Interacts (via the GTPase and B domains) with UBE2I; the interaction promotes sumoylation of DNM1L, mainly in its B domain. Interacts with PPP3CA; the interaction dephosphorylates DNM1L and regulates its transition to mitochondria. Interacts with BCL2L1 isoform BCL-X(L) and CLTA; DNM1L and BCL2L1 isoform BCL-X(L) may form a complex in synaptic vesicles that also contains clathrin and MFF. Interacts with MFF; the interaction is inhibited by C11orf65/MFI (PubMed:30059978). Interacts with FIS1. Interacts with MIEF2 and MIEF1; GTP-dependent, regulates GTP hydrolysis and DNM1L oligomerization (PubMed:24508339). Interacts with PGAM5; this interaction leads to dephosphorylation at Ser-656 and activation of GTPase activity and eventually to mitochondria fragmentation. Interacts with RALBP1; during mitosis, recruits DNM1L to the mitochondrion and mediates its activation by the mitotic kinase cyclin B-CDK1 (By similarity).|||Mitochondrion outer membrane|||Mutant mice show severe developmental abnormalities and die between 10.5 and 12.5 dpc. Compared to wild-type littermates, mutant embryos at 9.5-11.5 dpc have a significantly smaller body size, pulsing, but less developed cardiac structures, a poorly developed liver and a thinner neural tube cell layer. They lack trophoblastic giant cell layer in the placenta. Primary cultures of mutant neuronal cells have severe defects in synapse formation and high sensitivity to Ca(2+)-dependent apoptosis. Within cerebellar neurons, Purkinje cells are particularly sensitive to Dnm1l ablation. Conditional knockout in postmitotic Purkinje cells leads to 40% neuronal degeneration after 3 months and 90% after 6 months.|||O-GlcNAcylation augments the level of the GTP-bound active form of DNM1L and induces translocation from the cytoplasm to mitochondria in cardiomyocytes. It also decreases phosphorylation at Ser-643 (By similarity).|||Peroxisome|||Phosphorylation/dephosphorylation events on two sites near the GED domain regulate mitochondrial fission (By similarity). Phosphorylation on Ser-643 inhibits mitochondrial fission probably through preventing intramolecular interaction (By similarity). Dephosphorylated on this site by PPP3CA which promotes mitochondrial fission (By similarity). Phosphorylation on Ser-622 by Pink1 activates the GTPase activity and promotes mitochondrial fission (PubMed:32484300). Phosphorylated in a circadian manner at Ser-643 (By similarity).|||S-nitrosylation increases DNM1L dimerization, mitochondrial fission and causes neuronal damage.|||Sumoylated on various lysine residues within the B domain, probably by MUL1. Sumoylation positively regulates mitochondrial fission. Desumoylated by SENP5 during G2/M transition of mitosis. Appears to be linked to its catalytic activity (By similarity).|||The GED domain folds back to interact, in cis, with the GTP-binding domain and middle domain, and interacts, in trans, with the GED domains of other DNM1L molecules, and is thus critical for activating GTPase activity and for DNM1L dimerization.|||Ubiquitination by MARCHF5 affects mitochondrial morphology.|||clathrin-coated pit|||cytosol|||synaptic vesicle membrane http://togogenome.org/gene/10090:Tmf1 ^@ http://purl.uniprot.org/uniprot/B9EKI3 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Component of the SNF/SWI transcription factor complexes (By similarity). Interacts with RAB6A. Interacts with TCEB1 (By similarity). Interacts with STAT3 and FER. Interacts with TRNP1; may regulate TRNP1 proteasomal degradation.|||Cytoplasm|||Golgi apparatus membrane|||Nucleus|||Phosphorylated by FER.|||Potential coactivator of the androgen receptor. May play critical roles in two RAB6-dependent retrograde transport processes: one from endosomes to the Golgi and the other from the Golgi to the ER (By similarity). Mediates STAT3 degradation.|||The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV]. http://togogenome.org/gene/10090:Srfbp1 ^@ http://purl.uniprot.org/uniprot/Q9CZ91 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Highly expressed in heart, skeletal muscle, liver, kidney, testis and brain. Also expressed in white adipose tissue. Expression is up-regulated in cardiomyopathic heart.|||Interacts with SRF. Forms complexes with SRF and SRF cofactors ARID2, MYOCD and NKX2-5. Interacts with the N-terminus of SLC2A4.|||May be involved in regulating transcriptional activation of cardiac genes during the aging process. May play a role in biosynthesis and/or processing of SLC2A4 in adipose cells.|||Up-regulated in adult heart (at protein level).|||perinuclear region http://togogenome.org/gene/10090:Crtc1 ^@ http://purl.uniprot.org/uniprot/Q68ED7 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TORC family.|||Binds, as a tetramer, through its N-terminal region, with the bZIP domain of CREB1 (By similarity). 'Arg-314' in the bZIP domain of CREB1 is essential for this interaction (By similarity). Interaction, via its C-terminal, with TAF4, enhances recruitment of TAF4 to CREB1 (By similarity). Interacts with 14-3-3 proteins, including YWHAE/14-3-3 epsilon (PubMed:28235073, PubMed:30611118). Interacts with calmodulin-dependent catalytic subunit PPP3CA/calcineurin A (PubMed:30611118).|||Cytoplasm|||Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain. Expression is highest during the day and reaches a nadir during the early subjective night.|||Highly expressed in specific regions of the brain including the cortex, hippocampus and striatum.|||Nucleus|||Phosphorylation/dephosphorylation states of Ser-151 are required for regulating transduction of CREB activity. TORCs are inactive when phosphorylated, and active when dephosphorylated at this site. This primary site of phosphorylation is mediated by SIKs (SIK1 and SIK2), is regulated by cAMP and calcium levels and is dependent on the phosphorylation of SIKs by LKB1.|||Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites (PubMed:29211348). Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated (PubMed:29211348). Acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells (By similarity). In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons. In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock. http://togogenome.org/gene/10090:Ndfip2 ^@ http://purl.uniprot.org/uniprot/M0QWK1|||http://purl.uniprot.org/uniprot/Q3V1V0 ^@ Subcellular Location Annotation ^@ Endosome membrane|||Membrane http://togogenome.org/gene/10090:Arhgef1 ^@ http://purl.uniprot.org/uniprot/E9PUF7|||http://purl.uniprot.org/uniprot/Q61210 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Interacts with RHOA, GNA12 and GNA13 (By similarity). Homooligomerizes through the coiled coil region. Interacts with CTNNAL1 (By similarity). May interact with CCPG1.|||Membrane|||Mice have reduced response to angiotensin-2 and lowered RhoA signaling pathway.|||Phosphorylated by PKCA (By similarity). Angiotensin-2 induced Tyr-737 phosphorylation is mediated by JAK2. Isoform 5 is phosphorylated at 'Ser-390'.|||Ref.2 sequence was originally submitted as from rat origin.|||Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits. Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase. Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain. This GEF activity is inhibited by binding to activated GNA12. Mediates angiotensin-2-induced RhoA activation. Isoform 3 and isoform 4 do not homooligomerize and show an enhanced RhoGEF activity.|||The DH domain is involved in interaction with CCPG1.|||The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for full GAP activity.|||Ubiquitously expressed. http://togogenome.org/gene/10090:Or5aq6 ^@ http://purl.uniprot.org/uniprot/A2AT96 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bcan ^@ http://purl.uniprot.org/uniprot/Q61361 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aggrecan/versican proteoglycan family.|||Expressed in the retina, specifically around the inner and outer segments of photoreceptors, retinal pigment epithelium, outer plexiform layer, and the ganglion cell layer (at protein level) (PubMed:29777959). Brain (PubMed:9286696, PubMed:14550776, PubMed:22121037). Expressed in the brainstem and cerebellum in a perineuronal net pattern (PubMed:14550776, PubMed:22121037).|||Interacts with TNR.|||May play a role in the terminally differentiating and the adult nervous system during postnatal development. Could stabilize interactions between hyaluronan (HA) and brain proteoglycans.|||O-glycosylated; contains chondroitin sulfate.|||Secreted|||extracellular matrix http://togogenome.org/gene/10090:Socs5 ^@ http://purl.uniprot.org/uniprot/O54928 ^@ Developmental Stage|||Domain|||Function|||Induction|||PTM|||Subunit|||Tissue Specificity ^@ By a subset of cytokines including IL6 and LIF.|||During embryonic development, expressed from mid-to-late gestation and in yolk sac.|||Interacts with EGFR. Interacts with ELOB and ELOC; mediates EGFR ubiquitination and degradation (By similarity). Interacts with IL4R; inhibits IL4 signaling.|||Phosphorylated. Phosphorylation is induced by EGF (By similarity).|||SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. May be a substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits for instance EGF signaling by mediating the degradation of the EGF receptor/EGFR. Involved in the regulation of T-helper cell differentiation by inhibiting of the IL4 signaling pathway which promotes differentiation into the Th2 phenotype. Can also partially inhibit IL6 and LIF signaling.|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.|||Widely expressed. Expressed in TH1 but not TH2 cells. http://togogenome.org/gene/10090:6030468B19Rik ^@ http://purl.uniprot.org/uniprot/Q9CX63 ^@ Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Tissue Specificity ^@ Expressed in bone marrow, spleen and lymph node (PubMed:28978694).|||Mice are viable and reproduce normally (PubMed:28978694). Show reduced number of both peripheral lymphocyte B cells in the spleen and precursor and mature lymphocyte B cells in the bone marrow (PubMed:28978694). Show smaller and fewer Peyer's patches, lower numbers of immunoglobulin/IgA-secreting B cells and an altered gut microbiome (PubMed:28978694). Exhibit reduced levels of immunoglobulin/IgA in the serum, gut, feces, and lactating mammary gland (PubMed:28978694).|||Probable B cell-associated cytokine that plays a role in the regulation of humoral immune responses (PubMed:28978694). Involved in lymphocyte B cell development and immunoglobulin/IgA production (PubMed:28978694).|||Secreted|||Up-regulated in the mammary gland upon the onset of lactation (PubMed:28978694). Up-regulated in peripheral blood lymphocyte B cells upon activation (PubMed:28978694). http://togogenome.org/gene/10090:Plp2 ^@ http://purl.uniprot.org/uniprot/Q0VEW4|||http://purl.uniprot.org/uniprot/Q9R1Q7 ^@ Function|||Subcellular Location Annotation ^@ May play a role in cell differentiation in the intestinal epithelium.|||Membrane http://togogenome.org/gene/10090:Maob ^@ http://purl.uniprot.org/uniprot/Q8BW75 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the flavin monoamine oxidase family.|||Catalyzes the oxidative deamination of primary and some secondary amines such as neurotransmitters, and exogenous amines including the tertiary amine, neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with concomitant reduction of oxygen to hydrogen peroxide and participates in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:4156831). Preferentially degrades benzylamine and phenylethylamine (By similarity).|||Mitochondrion outer membrane|||Monomer, homo- or heterodimer (containing two subunits of similar size). Each subunit contains a covalently bound flavin. Enzymatically active as monomer (By similarity). http://togogenome.org/gene/10090:C8b ^@ http://purl.uniprot.org/uniprot/Q8BH35 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complement C6/C7/C8/C9 family.|||Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.|||Heterotrimer of 3 chains: alpha, beta and gamma. The alpha and gamma chains are disulfide bonded. Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b sequentially binds C6, C7, C8 and multiple copies of the pore-forming subunit C9 (By similarity).|||Secreted http://togogenome.org/gene/10090:Nup210 ^@ http://purl.uniprot.org/uniprot/Q9QY81 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NUP210 family.|||Endoplasmic reticulum membrane|||Forms dimers and possibly higher-order oligomers.|||N-glycosylated, but not all potential glycosylation sites may be used. Contains high-mannose type oligosaccharides (By similarity).|||Nucleoporin essential for nuclear pore assembly and fusion, nuclear pore spacing, as well as structural integrity.|||Nucleus membrane|||Phosphorylated at Ser-1880 in mitosis specifically; not phosphorylated in interphase.|||Preferential expressed in epithelial cells. In the kidney, expression was seen in both the epithelium derived from the ureteric tree and the mesenchyme-derived epithelium. In other tissues of 13-day-old embryos, expression was also confined to the epithelium. In nervous tissues, mainly expressed in the olfactory epithelium and walls of the lateral ventricle. Weak expression was seen in the heart.|||nuclear pore complex http://togogenome.org/gene/10090:Jade2 ^@ http://purl.uniprot.org/uniprot/Q6ZQF7 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subunit ^@ Belongs to the JADE family.|||Component of the HBO1 complex composed at least of ING4 or ING5, MYST2/HBO1, MEAF6, and one of JADE1, JADE2 and JADE3 (By similarity). Interacts (via C-terminus) with KDM1A (via AOD/Tower domain) (PubMed:25018020).|||Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity (By similarity). Acts as a E3 ubiquitin-protein ligase mediating the ubiquitination and subsequent proteasomal degradation of target protein histone demethylase KDM1A (PubMed:25018020). Also acts as a ubiquitin ligase E3 toward itself (PubMed:25018020). Positive regulator of neurogenesis (PubMed:25018020).|||Strongly decreased level of KDM1A polyubiquitination resulting in increased level of KDM1A protein. Decelerated emergence of neural progenitors and mature neurons. Embryonic stem cells grow in aggregates with smoother-edged, rounder-shaped cell clones and fail to organize in rosettes with surrounding cells exhibiting neuronal morphology with extensive arborization. Decreased expression of neural markers.|||The first PHD domain is essential for its E3 ubiquitin ligase activity. http://togogenome.org/gene/10090:Spns3 ^@ http://purl.uniprot.org/uniprot/Q9D232 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.|||Membrane|||Sphingolipid transporter. http://togogenome.org/gene/10090:Pdcl ^@ http://purl.uniprot.org/uniprot/Q9DBX2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phosducin family.|||Conditional deletion in photoreceptor cells leads to 50-fold decrease in Gbeta-Ggamma dimer formation and more than 10-fold decrease in light sensitivity. A 20-fold reduction in Gbeta5 and RGS9-1 expression is also observed, causing a 15-fold delay in the shutoff of light responses.|||Forms a complex with the beta and gamma subunits of the GTP-binding protein, transducin. Interacts with the CCT chaperonin complex (By similarity).|||Functions as a co-chaperone for CCT in the assembly of heterotrimeric G protein complexes, facilitates the assembly of both Gbeta-Ggamma and RGS-Gbeta5 heterodimers (PubMed:23637185). Acts also as a positive regulator of hedgehog signaling and regulates ciliary function (PubMed:29290584).|||cilium http://togogenome.org/gene/10090:Stk10 ^@ http://purl.uniprot.org/uniprot/A1A553|||http://purl.uniprot.org/uniprot/O55098 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylates following homodimerization, leading to activation of the protein.|||Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cell membrane|||Expressed predominantly in lymphoid organs such as spleen, thymus, and bone marrow.|||Homodimer; homodimerization is required for activation segment autophosphorylation.|||Inhibited by the pyrrole-indolinone inhibitor SU11274 (K00593): intercalates between the ATP-binding Lys-65 and alpha-C glutamate (Glu-81), resulting in a partial disordering of the lysine side chain. Also specifically inhibited by erlotinib. Slightly inhibited by gefitinib (By similarity).|||Mice do not show any obvious abnormalities. Lymphocytes develop normally but activated lymphocytes show enhanced cell adhesion. Decreased phosphorylation of ERM proteins.|||Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. http://togogenome.org/gene/10090:Tmem86b ^@ http://purl.uniprot.org/uniprot/Q497J1 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TMEM86 family.|||Catalyzes the hydrolysis of the vinyl ether bond of choline or ethanolamine lysoplasmalogens, forming fatty aldehyde and glycerophosphocholine or glycerophosphoethanolamine, respectively and is specific for the sn-2-deacylated (lyso) form of plasmalogen.|||Competitively inhibited by lysophosphatidic acid.|||Cytoplasm|||Endoplasmic reticulum membrane|||Enriched in liver. Also detected in brain and testis.|||Expressed in embryo.|||Homodimer. http://togogenome.org/gene/10090:Drc1 ^@ http://purl.uniprot.org/uniprot/Q3USS3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 7.5 dpc, expressed in the pit cells of the node, which carry motile cilia and are involved in left-right axis development.|||Belongs to the DRC1 family.|||Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Plays a critical role in the assembly of N-DRC and also stabilizes the assembly of multiple inner dynein arms and radial spokes (PubMed:34169321). Coassembles with CCDC65/DRC2 to form a central scaffold needed for assembly of the N-DRC and its attachment to the outer doublet microtubules.|||Component of the nexin-dynein regulatory complex (N-DRC). Interacts with CCDC65/DRC2, DRC3, GAS8/DRC4 and TCTE1/DRC5.|||Knockout mice on a C57BL/6 background experience pre-puberal death, usually before postnatal day 12, and exhibit signs of growth retardation and hydrocephaly. Mutant mice on C57BL/6 x ICR background can survive to adulthood, are infertile, and have reduced sperm counts with short or absent flagella.|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Tomm7 ^@ http://purl.uniprot.org/uniprot/Q9D173 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Tom7 family.|||Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) which consists of at least 7 different proteins (TOMM5, TOMM6, TOMM7, TOMM20, TOMM22, TOMM40 and TOMM70).|||Mitochondrion outer membrane|||Required for assembly and stability of the TOM complex (By similarity). Positive regulator of PRKN translocation to damaged mitochondria. Acts probably by stabilizing PINK1 on the outer membrane of depolarized mitochondria (By similarity). http://togogenome.org/gene/10090:Il36rn ^@ http://purl.uniprot.org/uniprot/Q9QYY1 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IL-1 family.|||Bioactive (processed) recombinant IL36RN inhibits effects of IL-36 when used in 100- 1000-fold molar excess.|||Cytoplasm|||Highly abundant in embryonic tissue and tissues containing epithelial cells.|||In combination with transgenic IL36A exacerbates skin abnormalities (acanthosis, hyperkeratosis, presence of a mixed inflammatory cell infiltrate and increased cytokine and chemokine expression).|||Inhibits the activity of interleukin-36 (IL36A,IL36B and IL36G) by binding to receptor IL1RL2/IL-36R and preventing its association with the coreceptor IL1RAP for signaling. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor. Proposed to play a role in skin inflammation. May be involved in the innate immune response to fungal pathogens. May activate an anti-inflammatory signaling pathway by recruiting SIGIRR.|||Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion.|||Removal of N-terminal methionine is necessary for full antagonistic activity.|||Secreted http://togogenome.org/gene/10090:Ctr9 ^@ http://purl.uniprot.org/uniprot/Q62018 ^@ Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription (By similarity). Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3.|||Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (By similarity). The PAF1 complex interacts with PHF5A (PubMed:27749823). Interacts with KMT2A/MLL1 (By similarity). Interacts with STAT3 (PubMed:17911113). Interacts with SETD5 (PubMed:27864380). Interacts with ERCC6 (By similarity).|||Contaminating sequence. Potential poly-A sequence starting in position 937.|||Nucleus speckle|||Widely expressed. http://togogenome.org/gene/10090:Sf3b1 ^@ http://purl.uniprot.org/uniprot/G5E866|||http://purl.uniprot.org/uniprot/Q3US00|||http://purl.uniprot.org/uniprot/Q8C839 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the SF3B1 family.|||Nucleus http://togogenome.org/gene/10090:Lztr1 ^@ http://purl.uniprot.org/uniprot/Q9CQ33 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the LZTR1 family.|||Embryonic lethality between 17.5 dpc and birth (PubMed:30442762). Impaired ubiquitination of Ras (K-Ras/Kras, N-Ras/Nras and H-Ras/Hras) (PubMed:30442762). Heterozygous mice display heart malformations, including decreased left ventricular systolic function, increased diastolic dimensions, eccentric hypertrophy, increased cardiomyocyte area and reduced longevity; phenotypes that are reminiscent of human Noonan Syndrome (PubMed:30442762).|||Endomembrane system|||Golgi apparatus|||Homodimer. Component of the BCR(LZTR1) E3 ubiquitin ligase complex, at least composed of CUL3, LZTR1 and RBX1. Interacts with Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS). Interacts with RAF1. Interacts with SHOC2. Interacts with PPP1CB.|||May result from the retention of an intron in the cDNA in position 800.|||Phosphorylated on tyrosine upon induction of apoptosis, leading to its degradation by the proteasome.|||Recycling endosome|||Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates ubiquitination of Ras (K-Ras/KRAS, N-Ras/NRAS and H-Ras/HRAS) (PubMed:30442762). Is a negative regulator of RAS-MAPK signaling that acts by controlling Ras levels and decreasing Ras association with membranes (PubMed:30442762).|||Widely expressed. http://togogenome.org/gene/10090:Ddt ^@ http://purl.uniprot.org/uniprot/O35215|||http://purl.uniprot.org/uniprot/Q3UNI8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MIF family.|||Cytoplasm|||Homotrimer.|||Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI). http://togogenome.org/gene/10090:Fgf8 ^@ http://purl.uniprot.org/uniprot/D3Z207|||http://purl.uniprot.org/uniprot/P37237|||http://purl.uniprot.org/uniprot/Q3V279|||http://purl.uniprot.org/uniprot/Q80ZL6 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Absent in normal mammary glands and detected only in adult testis and ovary and in midgestational embryos.|||Belongs to the heparin-binding growth factors family.|||By androgens.|||Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors (By similarity).|||Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryogenesis. Required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Plays a role in neurite outgrowth in hippocampal cells (By similarity). Cooperates with Wnt-1 in mouse mammary tumor virus-induced murine mammary tumorigenesis (PubMed:7884899).|||Secreted|||The N-terminus is blocked. http://togogenome.org/gene/10090:Pth ^@ http://purl.uniprot.org/uniprot/Q9Z0L6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the parathyroid hormone family.|||Interacts with PTH1R (via N-terminal extracellular domain).|||PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells.|||Secreted http://togogenome.org/gene/10090:AI182371 ^@ http://purl.uniprot.org/uniprot/A2AS37|||http://purl.uniprot.org/uniprot/Q8BWN9|||http://purl.uniprot.org/uniprot/Q8BWS8 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Hpca ^@ http://purl.uniprot.org/uniprot/P84075 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the recoverin family.|||Binds 3 calcium via EF-hand domains. The cryptic EF-hand 1 does not bind calcium.|||Calcium-binding protein that may play a role in the regulation of voltage-dependent calcium channels. May also play a role in cyclic-nucleotide-mediated signaling through the regulation of adenylate and guanylate cyclases.|||Membrane|||Myristoylation facilitates association with membranes.|||Oligomer; oligomerization is calcium-dependent. May interact with the voltage-dependent P/Q- and N-type calcium channels CACNA1A and CACNA1B.|||cytosol http://togogenome.org/gene/10090:Aldh7a1 ^@ http://purl.uniprot.org/uniprot/Q9DBF1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldehyde dehydrogenase family.|||Homotetramer.|||Mitochondrion|||Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.|||Nucleus|||Present in liver, kidney, brain and pancreas, and at lower levels in jejunum, duodenum, stomach and testes (at protein level).|||cytosol http://togogenome.org/gene/10090:Vmn1r132 ^@ http://purl.uniprot.org/uniprot/E9Q8L6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Nol7 ^@ http://purl.uniprot.org/uniprot/Q9D7Z3 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ May be due to intron retention.|||Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.|||Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.|||nucleolus http://togogenome.org/gene/10090:Rpa1 ^@ http://purl.uniprot.org/uniprot/Q3U8B3|||http://purl.uniprot.org/uniprot/Q5SWN2|||http://purl.uniprot.org/uniprot/Q8VEE4 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage.|||As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Also plays a role in base excision repair (BER) probably through interaction with UNG. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance.|||Belongs to the replication factor A protein 1 family.|||Component of the canonical replication protein A complex (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3. The DNA-binding activity may reside exclusively on the RPA1 subunit. Interacts with PRPF19; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it ubiquitinates the replication protein A complex (RPA). Interacts with RIPK1. Interacts with the polymerase alpha subunit POLA1/p180; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp. Interacts with RAD51 and SENP6 to regulate DNA repair. Interacts with HELB; this interaction promotes HELB recruitment to chromatin following DNA damage. Interacts with PRIMPOL; leading to recruit PRIMPOL on chromatin and stimulate its DNA primase activity. Interacts with XPA; the interaction is direct and associates XPA with the RPA complex. Interacts with ETAA1; the interaction is direct and promotes ETAA1 recruitment at stalled replication forks. Interacts with RPA1; this interaction associates HROB with the RPA complex (PubMed:31467087).|||Component of the heterotrimeric canonical replication protein A complex (RPA).|||DNA damage-induced 'Lys-63'-linked polyubiquitination by PRPF19 mediates ATRIP recruitment to the RPA complex at sites of DNA damage and activation of ATR. Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination.|||Nucleus|||PML body|||Sumoylated on lysine residues Lys-458 and Lys-586, with Lys-458 being the major site. Sumoylation promotes recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. Desumoylated by SENP6 (By similarity). http://togogenome.org/gene/10090:Unc5cl ^@ http://purl.uniprot.org/uniprot/E9QLC2 ^@ Similarity ^@ Belongs to the unc-5 family. http://togogenome.org/gene/10090:Eif3i ^@ http://purl.uniprot.org/uniprot/Q9QZD9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit I family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex may interact with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation may lead to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm|||Phosphorylated by TGF-beta type II receptor. http://togogenome.org/gene/10090:Slc19a1 ^@ http://purl.uniprot.org/uniprot/P41438|||http://purl.uniprot.org/uniprot/Q542F3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Antiporter that mediates the import of reduced folates (PubMed:8276792, PubMed:8664315, PubMed:9111015, PubMed:9748272). Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates (By similarity). Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:8276792, PubMed:9111015). Also able to mediate the import of antifolate drug methotrexate (PubMed:8276792, PubMed:8664315, PubMed:9748272). 5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (By similarity).|||Apical cell membrane|||Basolateral cell membrane|||Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.|||Cell membrane|||In contrast to human, not able to transport immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol.|||Transporter that mediates the import of reduced folates. http://togogenome.org/gene/10090:Grk6 ^@ http://purl.uniprot.org/uniprot/A0A286YDA5|||http://purl.uniprot.org/uniprot/A0A286YDZ5|||http://purl.uniprot.org/uniprot/A0A286YE10|||http://purl.uniprot.org/uniprot/O70293|||http://purl.uniprot.org/uniprot/Q9EP84 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.|||Deficient mice show significant altered central dopamine receptors regulation, deficient lymphocyte chemotaxis and increased acute inflammation and neutrophil chemotaxis.|||Expressed in the brain in striatal neurons.|||Interacts with GIT1.|||Membrane|||Specifically phosphorylates the activated forms of G protein-coupled receptors. Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their desensitization. Seems to be involved in the desensitization of D2-like dopamine receptors in striatum and chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis (By similarity). Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro) (By similarity). http://togogenome.org/gene/10090:Ctu1 ^@ http://purl.uniprot.org/uniprot/Q99J10 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TtcA family. CTU1/NCS6/ATPBD3 subfamily.|||Component of a complex at least composed of URM1, CTU2/NCS2 and CTU1/ATPBD3. May form a heterodimer with CTU2/NCS2.|||Cytoplasm|||Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). Directly binds tRNAs and probably acts by catalyzing adenylation of tRNAs, an intermediate required for 2-thiolation. It is unclear whether it acts as a sulfurtransferase that transfers sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position. http://togogenome.org/gene/10090:Mex3b ^@ http://purl.uniprot.org/uniprot/F8WJD6 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Arhgap40 ^@ http://purl.uniprot.org/uniprot/E9Q6X9 ^@ Function ^@ GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. http://togogenome.org/gene/10090:Dpys ^@ http://purl.uniprot.org/uniprot/Q9EQF5 ^@ Cofactor|||Function|||PTM|||Similarity|||Subunit ^@ Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.|||Binds 2 Zn(2+) ions per subunit.|||Carboxylation allows a single lysine to coordinate two zinc ions.|||Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate (By similarity).|||Homotetramer. http://togogenome.org/gene/10090:Nlrp4c ^@ http://purl.uniprot.org/uniprot/Q3TKR3 ^@ Function|||Similarity ^@ Belongs to the NLRP family.|||May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. http://togogenome.org/gene/10090:Slc34a1 ^@ http://purl.uniprot.org/uniprot/Q9D2V6 ^@ Similarity|||Subcellular Location Annotation ^@ Apical cell membrane|||Belongs to the SLC34A transporter family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Foxf1 ^@ http://purl.uniprot.org/uniprot/Q61080 ^@ Caution|||Domain|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Activation domains C-terminal of (and distinct from) the forkhead domains are necessary for transcriptional activation.|||Expressed primarily in lung in alveolar type II pneumocyte cells, and to a lesser extent in placenta, stomach, intestine and colon.|||It is uncertain whether Met-1 or Met-26 is the initiator.|||Nucleus|||Probable transcription activator for a number of lung-specific genes. http://togogenome.org/gene/10090:Lbp ^@ http://purl.uniprot.org/uniprot/Q61805 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.|||Cytoplasmic granule membrane|||Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria (PubMed:9144073). Acts as an affinity enhancer for CD14, facilitating its association with LPS (By similarity). Promotes the release of cytokines in response to bacterial lipopolysaccharide (PubMed:24380872).|||Secreted|||When bound to LPS, interacts (via C-terminus) with soluble and membrane-bound CD14. http://togogenome.org/gene/10090:Or2ag17 ^@ http://purl.uniprot.org/uniprot/Q7TRN3 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:C1qtnf3 ^@ http://purl.uniprot.org/uniprot/Q9ES30 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Atrnl1 ^@ http://purl.uniprot.org/uniprot/Q6A051 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Highly expressed in brain, heart, lung, kidney and liver. In the central nervous system, it is highly expressed in the dentate gyrus, CA1-3 regions of the hippocampus, and the ventral taenia tecta.|||Interacts with MC4R.|||May play a role in melanocortin signaling pathways that regulate energy homeostasis.|||Mice are grossly normal with no alterations of pigmentation, central nervous system pathology or body weight. In contrast, constitutive expression of Atrnl1 in mice lacking Atrn display normal, agouti-banded hairs and significantly delayed onset of spongiform neurodegeneration, indicating that overexpression of Atrnl1 compensates for loss of Atrn. http://togogenome.org/gene/10090:Adam34 ^@ http://purl.uniprot.org/uniprot/A2RSG8 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Lta4h ^@ http://purl.uniprot.org/uniprot/P24527 ^@ Activity Regulation|||Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase M1 family.|||Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities (By similarity). Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:1881903, PubMed:9287304). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (By similarity). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (By similarity).|||Binds 1 zinc ion per subunit.|||Cytoplasm|||Deficient mice have normal phenotypes. Inflammatory reactions are reduced as are some other immunological responses.|||Inhibited by bestatin (By similarity). The epoxide hydrolase activity is restrained by suicide inactivation that involves binding of LTA4 to Tyr-379 (PubMed:9287304). 4-(4-benzylphenyl)thiazol-2-amine (ARM1) selectively inhibits the epoxide hydrolase activity (By similarity).|||Monomer.|||Phosphorylation at Ser-416 inhibits leukotriene-A4 hydrolase activity. http://togogenome.org/gene/10090:Zbtb11 ^@ http://purl.uniprot.org/uniprot/G5E8B9 ^@ Function|||Subcellular Location Annotation ^@ May be involved in transcriptional regulation.|||nucleolus http://togogenome.org/gene/10090:Prl2c2 ^@ http://purl.uniprot.org/uniprot/A0A0M6L0W4|||http://purl.uniprot.org/uniprot/P04095 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Endoplasmic reticulum|||Expressed at low levels during hair follicle morphogenesis, with highest expression levels detected at late anagen stage of the hair follicle cycle (PubMed:11316781). Expressed in developing brain from embryo to adult (PubMed:16876275). In placenta, detected at 8 dpc, peaks at 10 dpc and declines thereafter (PubMed:10537154).|||Expressed in brain and cerebellum (PubMed:16876275). Expressed in placenta and hair follicles, with highest expression levels detected in the outer root sheath and no expression detected in bulb (PubMed:11316781, PubMed:10537154). Also expressed in body fluids such as plasma and amniotic fluid (PubMed:10537154). Expressed in embryonic fibroblasts and at low levels in keratinocytes (PubMed:11316781). Isoform 1: Expressed in brain and Neuro-2a cells (PubMed:16876275). Isoform 2: Expressed in brain (PubMed:16876275).|||May have a role in embryonic development. It is likely to provide a growth stimulus to target cells in maternal and fetal tissues during the development of the embryo at mid-gestation. May play a role during wound healing and in the hair follicle cycle as a growth factor and/or an angiogenesis factor. May play a role in microvilli formation and cell proliferation of neuroblastoma cells.|||N-glycosylated and sialylated.|||Secreted http://togogenome.org/gene/10090:Emp2 ^@ http://purl.uniprot.org/uniprot/O88662|||http://purl.uniprot.org/uniprot/Q548I4|||http://purl.uniprot.org/uniprot/Q8BPC2 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the PMP-22/EMP/MP20 family.|||Cell membrane|||Cytoplasm|||Expressed from day 3 of gastrulation, expression peaks on day 6 before decreasing on days 8 and 10 (PubMed:30773261). Expressed throughout gestation in the embryo proper, trophoblastic stems cells in the ectoplacental cone and decidual cells (PubMed:28295343). Expressed in trophoblast giant cells and maternal decidua in the placenta and in the endometrium at 9.5 dpc (PubMed:28295343). Expressed in the developing heart, head and otic vesicle at 9.5 dpc (PubMed:30773261). Abundantly expressed in giant cells and weakly expressed in labyrinthine trophoblasts and spongiotrophoblasts in the junctional zone, also expressed within the cytoplasm and perinuclear region of pre-glycogen cells at 12 dpc (PubMed:28295343). Expression in all trophoblast populations reduces as placentas near term (PubMed:28295343).|||Expressed in alveolar epithelial type 1, alveolar epithelial type 2 and airway epithelial cells (at protein level) (PubMed:31550239). Expressed in both the endometrial epithelial and stromal cells during the embryo implantation period (PubMed:16487956). Expressed in the corneal epithelium, the sclera, the nerve fiber layer of the inner retina and retinal ganglion cell layer, the nonpigmented epithelium of the ciliary body and the optic nerve (PubMed:12710941).|||Functions as a key regulator of cell membrane composition by regulating protein surface expression. Also, plays a role in regulation of processes including cell migration, cell proliferation, cell contraction and cell adhesion. Regulates transepithelial migration of neutrophils into the alveolar lumen, potentially via mediation of cell surface expression of adhesion markers and lipid raft formation (PubMed:31550239). Negatively regulates caveolae formation by reducing CAV1 expression and CAV1 amount by increasing lysosomal degradation (PubMed:17609206, PubMed:14978215). Facilitates surface trafficking and the formation of lipid rafts bearing GPI-anchor proteins (PubMed:14978215). Regulates surface expression of MHC1 and ICAM1 proteins increasing susceptibility to T-cell mediated cytotoxicity (PubMed:12763482). Regulates the plasma membrane expression of the integrin heterodimers ITGA6-ITGB1, ITGA5-ITGB3 and ITGA5-ITGB1 resulting in modulation of cell-matrix adhesion (PubMed:12189152). Also regulates many processes through PTK2. Regulates blood vessel endothelial cell migration and angiogenesis by regulating VEGF protein expression through PTK2 activation (By similarity). Regulates cell migration and cell contraction through PTK2 and SRC activation (By similarity). Regulates focal adhesion density, F-actin conformation and cell adhesion capacity through interaction with PTK2 (By similarity). Positively regulates cell proliferation (By similarity). Plays a role during cell death and cell blebbing (By similarity). Promotes angiogenesis and vasculogenesis through induction of VEGFA via a HIF1A-dependent pathway (By similarity). Also plays a role in embryo implantation by regulating surface trafficking of integrin heterodimer ITGA5-ITGB3 (PubMed:16487956, PubMed:16216233). Plays a role in placental angiogenesis and uterine natural killer cell regulation at the maternal-fetal placental interface, however not required in the maternal tissues for a viable pregnancy (PubMed:28295343). Involved in the early stages of embryogenic development and cardiogenesis, potentially via regulation of epithelial-mesenchymal transition timing (PubMed:30773261). May play a role in glomerular filtration (By similarity).|||Functions as a key regulator of cell membrane composition by regulating proteins surface expression. Also, plays a role in regulation of processes including cell migration, cell proliferation, cell contraction and cell adhesion.|||Golgi apparatus membrane|||Induced by progesterone; initially expressed in the uterus luminal epithelium spreading to the glandular epithelium 48 hours after treatment, increases expression at the plasma membrane (PubMed:18400107). Induced by estradiol in the cytoplasm of endometrial tissue; expression is induced 48 hours after initiation of estradiol treatment (PubMed:18400107).|||Interacts with PTK2; regulates PTK2 activation and localization (By similarity). Interacts with ITGB3; regulates the levels of the heterodimer ITGA5-ITGB3 integrin surface expression (By similarity). Interacts with P2RX7 (via C-terminus) (By similarity). Interacts with ITGB1; the interaction may be direct or indirect and ITGB1 has a heterodimer form (PubMed:12189152).|||Knockout mice show a longer time to achieve pregnancy and a reduced litter size as a result of viable knockout embryos (PubMed:28295343). Increase in fibrin deposition throughout the decidua basalis and junctional zones in placentas (PubMed:28295343). Reduced placental vasculogenesis at 9.5dpc and altered vascular organization is evident at 12.5 dpc (PubMed:28295343). Increased collagen deposition in placentas including around the placental labyrinth at 16.5 dpc (PubMed:28295343). Increase in Hif1a expression in placental decidual leukocytes at 9.5 and 12.5 dpc, expression returns to normal by 16.5 dpc (PubMed:28295343). Increase in uterine natural killer cells in the placental decidua basalis throughout gestation (PubMed:28295343). Reduced influx of neutrophils to the airspace after intrapulmonary inoculation with the chemokine Cxcl1 and an increase in interstitial neutrophils in lipopolysaccharide challenged lungs (PubMed:31550239). Increased survival during K.pneumoniae lung infection, as a result of attenuated injury to the alveolocapillary barrier and decreased systemic inflammation (PubMed:31550239). Significant decrease in bacterial burden in the lungs, bloodstream, and spleen 48 hours following K.pneumoniae suggesting enhanced pathogen clearance in the lungs and reduced extrapulmonary dissemination (PubMed:31550239). Increase in surface Cd47 and decrease in surface Icam1 and Itgb3 on alveolar epithelial type 1 cells accompanied by a reduction in the number of lipid rafts (PubMed:31550239). Increase in Cav1 and Cav2 expression in lung tissues (PubMed:31550239).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Membrane raft|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Or51a5 ^@ http://purl.uniprot.org/uniprot/Q8VH13 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mvb12a ^@ http://purl.uniprot.org/uniprot/Q78HU3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MVB12 family.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with CD2AP and CIN85/SH3KBP1. Interacts with CD2AP (via one of the SH3 domains). Interacts with TSG101; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS28. Interacts with VPS37B; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37C; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with CEP55 (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor (By similarity).|||Endosome|||Late endosome membrane|||Nucleus|||Phosphorylated on Tyr-202 upon EGF stimulation. Phosphorylation is required for interaction with CD2AP and CIN85/SH3KBP1 (By similarity).|||centrosome|||cytoskeleton http://togogenome.org/gene/10090:Atp6v0d1 ^@ http://purl.uniprot.org/uniprot/P51863 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the V-ATPase V0D/AC39 subunit family.|||Expressed throughout early development.|||Lysosome membrane|||Membrane|||Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:12963731). V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells, thus providing most of the energy required for transport processes in the vacuolar system (By similarity). May play a role in coupling of proton transport and ATP hydrolysis (PubMed:12963731). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (By similarity). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (By similarity).|||Ubiquitous.|||V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with ATP6AP2; ATP6AP2 is a V-ATPase accessory protein and the interaction promotes v-ATPase complex assembly (By similarity). Interacts with TMEM9; TMEM9 is a v-ATPase assembly regulator and the interaction induces the interaction with ATP6AP2 (By similarity). Interacts with PIP4P1 (PubMed:29644770).|||clathrin-coated vesicle membrane http://togogenome.org/gene/10090:Col6a1 ^@ http://purl.uniprot.org/uniprot/Q04857 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type VI collagen family.|||Collagen VI acts as a cell-binding protein.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-4(VI) or alpha-5(VI) or alpha-6(VI).|||extracellular matrix http://togogenome.org/gene/10090:Vmn1r103 ^@ http://purl.uniprot.org/uniprot/K7N6X7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rprd1a ^@ http://purl.uniprot.org/uniprot/Q8VDS4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UPF0400 (RTT103) family.|||Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle.|||May form a heterodimer with RPRD1B. Associates with the RNA polymerase II subunit POLR2A (via CTD phosphorylated at 'Ser-2' and 'Ser-7' of the heptad repeats).|||Nucleus http://togogenome.org/gene/10090:Lipm ^@ http://purl.uniprot.org/uniprot/Q8K2A6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Plays a highly specific role in the last step of keratinocyte differentiation. May have an essential function in lipid metabolism of the most differentiated epidermal layers (By similarity).|||Secreted http://togogenome.org/gene/10090:Ccna2 ^@ http://purl.uniprot.org/uniprot/P51943 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Interacts with mouse cytomegalovirus/MCMV kinase M97; this interaction sequesters CCNA2 to the cytoplasm.|||Accumulates steadily during G2 and is abruptly destroyed at mitosis. Expressed in spermatogonia and is most abundant in preleptotene spermatocytes, cells which will enter the meiotic pathway.|||Belongs to the cyclin family. Cyclin AB subfamily.|||Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 and CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle.|||Cytoplasm|||Interacts with the CDK1 and CDK2 protein kinases to form serine/threonine kinase holoenzyme complexes (PubMed:10068472). Interacts with CDK1 (hyperphosphorylated form in G1 and underphosphorylated forms in S and G2). Interacts with CDK2; the interaction increases from G1 to G2. Interacts (associated with CDK2 but not with CDK1) with SCAPER; regulates the activity of CCNA2/CDK2 by transiently maintaining CCNA2 in the cytoplasm. Forms a ternary complex with CDK2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements (By similarity). Interacts with INCA1 (By similarity).|||Nucleus|||Polyubiquitinated via 'Lys-11'-linked ubiquitin by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome. Deubiquitinated and stabilized by USP37 enables entry into S phase.|||Ubiquitous (PubMed:8565853). In the testis, expressed in germ cells and in the ovary, in both germline and somatic cells (PubMed:8575639, PubMed:10068472). http://togogenome.org/gene/10090:Tktl2 ^@ http://purl.uniprot.org/uniprot/Q9D4D4 ^@ Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the transketolase family.|||Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+).|||Binds 1 thiamine pyrophosphate per subunit.|||Homodimer.|||Plays an essential role in total transketolase activity and cell proliferation in cancer cells; after transfection with anti-TKTL1 siRNA, total transketolase activity dramatically decreases and proliferation was significantly inhibited in cancer cells. Plays a pivotal role in carcinogenesis (By similarity). http://togogenome.org/gene/10090:Ankrd13b ^@ http://purl.uniprot.org/uniprot/Q5F259 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cell membrane|||Early endosome|||Interacts with EGFR (ubiquitinated); the interaction is direct and may regulate EGFR internalization.|||Late endosome|||Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane (By similarity). http://togogenome.org/gene/10090:Hoxa9 ^@ http://purl.uniprot.org/uniprot/P09631 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Abd-B homeobox family.|||Cytoplasm|||Expressed in high level in the embryonic and adult spinal cord with a preference in the posterior region.|||Methylated on Arg-140 by PRMT5; methylation is critical for E-selectin induction.|||Nucleus|||Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Required for induction of SELE/E-selectin and VCAM1 on the endothelial cell surface at sites of inflammation (By similarity). Positively regulates EIF4E-mediated mRNA nuclear export and also increases the translation efficiency of ODC mRNA in the cytoplasm by competing with factors which repress EIF4E activity such as PRH (PubMed:15657436).|||Transiently interacts with PRMT5 in TNF-alpha stimulated endothelial cells (By similarity). Interacts with EIF4E (PubMed:15657436). http://togogenome.org/gene/10090:Trim10 ^@ http://purl.uniprot.org/uniprot/Q9WUH5 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||Deletion mice inhibit hypertrophic remodeling after transverse aortic constriction surgery.|||E3 ligase that plays an essential role in the differentiation and survival of terminal erythroid cells (PubMed:18560381). May directly bind to PTEN and promote its ubiquitination, resulting in its proteasomal degradation and activation of hypertrophic signaling (PubMed:32343488). In addition, plays a role in immune response regulation by repressing the phosphorylation of STAT1 and STAT2 in the interferon/JAK/STAT signaling pathway independent of its E3 ligase activity. Mechanistically, interacts with the intracellular domain of IFNAR1 and thereby inhibits the association between TYK2 and IFNAR1 (By similarity).|||Expressed in embryonic liver.|||Interacts with IFNAR1; this interaction prevents association of IFNAR1 with TYK2. http://togogenome.org/gene/10090:Xylt1 ^@ http://purl.uniprot.org/uniprot/F8VPK6|||http://purl.uniprot.org/uniprot/Q811B1 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glycosyltransferase 14 family. XylT subfamily.|||Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN. Transfers D-xylose from UDP-D-xylose to specific serine residues of the core protein. Required for normal maturation of chondrocytes during bone development, normal onset of ossification and normal embryonic and postnatal skeleton development, especially of the long bones.|||Contains 7 disulfide bonds.|||Detected in brain, spleen, kidney and testis, and at low levels in skeletal muscle.|||Detected in embryonic chondrocytes in humerus and ulna during embryonic bone development. Not detected in mature bone.|||Golgi apparatus membrane|||Membrane|||Monomer.|||N-glycosylated. http://togogenome.org/gene/10090:Cacna1c ^@ http://purl.uniprot.org/uniprot/A0A087WS40|||http://purl.uniprot.org/uniprot/A0A087WSE7|||http://purl.uniprot.org/uniprot/C7TQ57|||http://purl.uniprot.org/uniprot/C7TQ58|||http://purl.uniprot.org/uniprot/C7TQ59|||http://purl.uniprot.org/uniprot/C7TQ60|||http://purl.uniprot.org/uniprot/C7TQ61|||http://purl.uniprot.org/uniprot/C7TQ62|||http://purl.uniprot.org/uniprot/F7C376|||http://purl.uniprot.org/uniprot/F8WJL1|||http://purl.uniprot.org/uniprot/Q01815|||http://purl.uniprot.org/uniprot/Q0PCR6 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.|||Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel.|||Cell membrane|||Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta subunits. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains only one of each type of subunit. CACNA1C channel activity is modulated by ancillary subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4 (By similarity). Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8 (By similarity). Interacts with CACNB1 (By similarity). Interacts with CACNB2. Identified in a complex with CACNA2D4 and CACNB3. Interacts with CACNB3. Interacts with CACNA2D1. Interacts with CACNA2D4. Interacts with CALM1. Interacts (via the N-terminus and the C-terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)-dependent channel inactivation. The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium and is mutually exclusive with calmodulin binding (By similarity). The binding to the cytoplasmic N-terminal domain is calcium independent but is essential for the channel modulation (By similarity). Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent manner (PubMed:18586882). Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy (PubMed:20639889). Interacts with STAC2 and STAC3; this inhibits channel inactivation (By similarity).|||Detected in embryonic heart (PubMed:10973973, PubMed:21216955). Detected in retina in rod bipolar cells (PubMed:18586882). Detected in tibialis artery (at protein level) (PubMed:14609949). Detected in smooth muscle cells from tibialis artery and in mesenteric artery (PubMed:14609949). High expression in heart, followed by brain and spinal cord (PubMed:1385406).|||Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.|||Inhibited by dihydropyridines (DHP), such as isradipine (PubMed:14609949, PubMed:21216955). Inhibited by nifedipine. Channel activity is regulated by Ca(2+) and calmodulin. Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function. Shear stress and pressure increases calcium channel activity (By similarity).|||Membrane|||Mutant embryos appear normal and have normal heartbeat at 12.5 dpc. All are dead by 14.5 dpc.|||Perikaryon|||Phosphorylation by PKA at Ser-1897 activates the channel (PubMed:28119464). Elevated levels of blood glucose lead to increased phosphorylation by PKA.|||Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:14609949, PubMed:18586882, PubMed:21216955, PubMed:25368181, PubMed:28119464). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:21216955). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:14609949, PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable).|||Postsynaptic density membrane|||T-tubule|||Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death.|||dendrite|||sarcolemma http://togogenome.org/gene/10090:Gpa33 ^@ http://purl.uniprot.org/uniprot/Q9JKA5 ^@ Function|||PTM|||Subcellular Location Annotation ^@ May play a role in cell-cell recognition and signaling.|||Membrane|||Palmitoylated. http://togogenome.org/gene/10090:Sun1 ^@ http://purl.uniprot.org/uniprot/Q9D666 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton (PubMed:20711465, PubMed:16380439, PubMed:24062341, PubMed:25892231, PubMed:26842404). The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (PubMed:19874786). Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration (PubMed:19874786). Involved in telomere attachment to nuclear envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly (PubMed:17543860, PubMed:19211677, PubMed:19509342, PubMed:24062341, PubMed:25892231, PubMed:26842404). Required for gametogenesis and involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis (PubMed:17543860). Helps to define the distribution of nuclear pore complexes (NPCs) (PubMed:17724119). Required for efficient localization of SYNE4 in the nuclear envelope (PubMed:23348741). May be involved in nuclear remodeling during sperm head formation in spermatogenesis (PubMed:20711465). May play a role in DNA repair by suppressing non-homologous end joining repair to facilitate the repair of DNA cross-links (By similarity).|||Core component of the LINC complex which is composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents is giving rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. Interacts with KASH5 (via the last 22 amino acids); this interaction mediates KASH5 telomere localization by forming a SUN1:KASH5 LINC complex. Isoform 5 is proposed to form a non-nuclear spermatogenesis-specific LINC complex with SYNE3 during sperm head formation. Interacts with SYNE2 and SYNE1; probably forming respective LINC complexes. Interacts with A-type lamin with a strong preference for unprocessed A-type lamin compared with the mature protein. Interaction with lamins B1 and C is hardly detectable. Interacts with NAT10. Interacts with EMD and TSNAX. Associates with the nuclear pore complex (NPC). Interacts with CCDC79/TERB1; promoting the accumulation of the LINC complex complexes at the telomere-nuclear envelope attachment sites. Interacts with IRAG2 (PubMed:29878215). Interacts (via KASH domain) with TMEM258 (By similarity).|||Isoform 5 may be involved in nuclear remodeling during sperm head formation in spermatogenesis. A probable SUN1 isoform 5:SYNE3 LINC complex may tether spermatid nuclei to anterior cytoskeletal structures such as actin filaments present at membraneous junctions of spermatids and Sertoli cells.|||Mutant mice are viable, but display hearing loss at all frequencies.|||Nucleus inner membrane|||The SUN domain may play a role in nuclear anchoring and/or migration.|||The coiled coil domains differentially mediate trimerization required for binding to nesprins and are proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation. The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton.|||The disulfide bond with KASH domain-containing nesprins is required for stability of the respective LINC complexes under tensile forces.|||Widely expressed. Expressed in cochlear outer hair cells (at protein level). Seven isoforms are expressed in testis including testis-specific isoform 5. Isoform 5 is the only isoform expressed at the end of sperm differentiation. Six isoforms are expressed in muscle, heart and brain, four isoforms in kidney and three isoforms in liver.|||acrosome outer membrane http://togogenome.org/gene/10090:Tubgcp3 ^@ http://purl.uniprot.org/uniprot/P58854 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TUBGCP family.|||Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 (By similarity). Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of TUBTUBGCP3 and CDK5RAP2 (By similarity). Interacts with NIN (via N-terminus); the interaction may promote recruitment of the gamma-tubulin ring complex to the centrosome (PubMed:15784680).|||Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.|||centrosome http://togogenome.org/gene/10090:Ndufa10 ^@ http://purl.uniprot.org/uniprot/Q99LC3 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Acetylation of Lys-242 is observed in liver mitochondria from fasted mice but not from fed mice.|||Belongs to the complex I NDUFA10 subunit family.|||Binds 1 FAD per subunit.|||Complex I is composed of 45 different subunits. This a component of the hydrophobic protein fraction.|||Mitochondrion matrix|||Phosphorylation at Ser-250 by PINK1 is required for the binding and/or reduction of the complex I substrate ubiquinone. http://togogenome.org/gene/10090:Cfl1 ^@ http://purl.uniprot.org/uniprot/P18760|||http://purl.uniprot.org/uniprot/Q544Y7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the actin-binding proteins ADF family.|||Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity (PubMed:11809832). In conjunction with the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:25208553). Required for the centralization of the mitotic spindle and symmetric division of zygotes (PubMed:25208553). Plays a role in the regulation of cell morphology and cytoskeletal organization in epithelial cells (By similarity). Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (By similarity). Required for neural tube morphogenesis and neural crest cell migration (PubMed:15649475).|||Can bind G- and F-actin in a 1:1 ratio of cofilin to actin (PubMed:11809832). It is a major component of intranuclear and cytoplasmic actin rods (By similarity). Interacts with the subcortical maternal complex (SCMC) via interaction with TLE6 and NLRP5 (PubMed:25208553). Interacts with C9orf72 (PubMed:27723745).|||In 10.5 dpc embryo somites is expressed in a ventral cell layer (myotome).|||Inactivated by phosphorylation on Ser-3. Phosphorylated on Ser-3 in resting cells (PubMed:25107909). Dephosphorylated by PDXP/chronophin; this restores its activity in promoting actin filament depolymerization. The phosphorylation of Ser-24 may prevent recognition of the nuclear localization signal (By similarity). Phosphorylated via a ARRB1-RAC1-LIMK1-PAK1 cascade upon active ligand stimulation of atypical chemokine receptor ACKR2 (By similarity).|||Nucleus matrix|||Widely distributed in various tissues. Not found in skeletal muscle.|||axon|||cytoskeleton|||growth cone|||lamellipodium|||lamellipodium membrane|||ruffle membrane http://togogenome.org/gene/10090:Slc16a3 ^@ http://purl.uniprot.org/uniprot/P57787|||http://purl.uniprot.org/uniprot/Q3TMA0|||http://purl.uniprot.org/uniprot/Q3UDP9 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Deficient mice are born at normal Mendelian ratio, with no apparent defects at birth. However mice exhibit impaired exercise endurance with abnormal neuromuscular junctions innervation and lower compound muscle action potential amplitude.|||Interacts with BSG; interaction mediates SLC16A3 targeting to the plasma membrane.|||Lateral cell membrane|||Membrane|||Proton-dependent transporter of monocarboxylates such as L-lactate and pyruvate (By similarity). Plays a predominant role in the L-lactate efflux from highly glycolytic cells (Probable).|||Two basolateral sorting signals (BSS) in its C-terminal cytoplasmic tail are required to direct SLC16A3 to the basolateral membrane.|||Was initially thought to be considered to be a low affinity lactate transporter with negligible affinity for pyruvate (By similarity). However, it was later shown that SLC16A3 is a high affinity lactate transporter with physiologically relevant affinity for pyruvate (By similarity). http://togogenome.org/gene/10090:Rps6ka2 ^@ http://purl.uniprot.org/uniprot/Q7TPD5|||http://purl.uniprot.org/uniprot/Q9WUT3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by phosphorylation at Ser-218 by PDPK1. Autophosphorylated on Ser-377, as part of the activation process. May be phosphorylated at Thr-356 and Ser-360 by MAPK1/ERK2 and MAPK3/ERK1 (By similarity).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.|||Cytoplasm|||Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in quiescent cells. Transiently dissociates following mitogenic stimulation (By similarity). Interacts with FBXO5; cooperate to induce the metaphase arrest of early blastomeres; increases and stabilizes interaction of FBXO5 with CDC20 (PubMed:15526037).|||N-terminal myristoylation results in an activated kinase in the absence of added growth factors.|||Nucleus|||Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells (By similarity).|||Upon extracellular signal or mitogen stimulation, phosphorylated at Thr-570 in the C-terminal kinase domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates Ser-377, allowing binding of PDPK1, which in turn phosphorylates Ser-218 in the N-terminal kinase domain (NTDK) leading to the full activation of the protein and subsequent phosphorylation of the substrates by the NTKD. http://togogenome.org/gene/10090:Trim45 ^@ http://purl.uniprot.org/uniprot/Q6PFY8 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||Deletion mutant mice show earlier onset of death and exhibit higher mortality in response to lethal challenge with LPS. The production of TNF-alpha, IL-6, and IL-1beta is also significantly up-regulated after TLR challenge.|||E3 ubiquitin-protein ligase that plays a role in the regulation of inflammatory response (PubMed:36681779). Mechanistically, mediates the 'Lys-48'-linked polyubiquitination of TAB2, a regulatory protein of the kinase TAK1, leading to its degradation via the proteasomal pathway and inhibition of the TLR-mediated inflammatory immune response. May act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway.|||Nucleus http://togogenome.org/gene/10090:Snx31 ^@ http://purl.uniprot.org/uniprot/Q6P8Y7 ^@ Function|||Similarity|||Subunit ^@ Belongs to the sorting nexin family.|||Interacts with CCDC22, CCDC93, VPS26C and VPS35L, associates with the retriever and CCC complexes.|||May be involved in protein trafficking. http://togogenome.org/gene/10090:Loxl1 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Q4|||http://purl.uniprot.org/uniprot/P97873 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Active on elastin and collagen substrates.|||Belongs to the lysyl oxidase family.|||Contains 1 lysine tyrosylquinone.|||Interacts (via propeptide) with EFEMP2.|||Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).|||The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.|||extracellular space http://togogenome.org/gene/10090:Pigf ^@ http://purl.uniprot.org/uniprot/O09101 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PIGF family.|||Endoplasmic reticulum membrane|||Forms a complex with PIGG and PIGO. PIGF is required to stabilize PIGG and PIGO.|||Involved in GPI-anchor biosynthesis through the transfer of ethanolamine phosphate to the third mannose of GPI. http://togogenome.org/gene/10090:Cc2d2a ^@ http://purl.uniprot.org/uniprot/Q8CFW7 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling.|||Cytoplasm|||Embryos show randomized left-right axes, holoprosencephaly, microphthalmia and a variably expressive curved body axis. Cc2d2a null embryos also have cilia defects, which are exemplified by the absence of Arl13b staining in neural tube and surrounding mesenchyme.|||Part of the tectonic-like complex (also named B9 complex).|||cilium basal body http://togogenome.org/gene/10090:Arhgef25 ^@ http://purl.uniprot.org/uniprot/Q9CWR0 ^@ Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Highly expressed in excitable tissues, such as brain, heart and muscle. Elevated expression in hippocampus and cerebellum.|||Interacts with activated GNAQ and GNA11 (By similarity). Interacts (via the DH domain) with BVES (via the C-terminus cytoplasmic tail). Interacts with RHOA, CDC42 and RAC1.|||May play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. It works as a guanine nucleotide exchange factor for Rho family of small GTPases. Links specifically G alpha q/11-coupled receptors to RHOA activation (By similarity). May be an important regulator of processes involved in axon and dendrite formation. In neurons seems to be an exchange factor primarily for RAC1. Involved in skeletal myogenesis.|||The guanine nucleotide exchange activity is autoinhibited by the PH domain.|||Transcriptionally up-regulated during myogenic differentiation and down-regulated during adipogenic differentiation. Protein levels up-regulated during retinoic acid and dibutyric cAMP-induced outgrowth of neurites.|||myofibril|||sarcomere http://togogenome.org/gene/10090:Ndufa6 ^@ http://purl.uniprot.org/uniprot/Q9CQZ5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. Required for proper complex I assembly. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.|||Belongs to the complex I LYR family.|||Mammalian complex I is composed of 45 different subunits.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Vipr1 ^@ http://purl.uniprot.org/uniprot/P97751 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 2 family.|||Cell membrane|||This is a receptor for VIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. http://togogenome.org/gene/10090:Atp8b1 ^@ http://purl.uniprot.org/uniprot/Q148W0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of phospholipids, in particular phosphatidylcholines (PC), from the outer to the inner leaflet of the plasma membrane (By similarity). May participate in the establishment of the canalicular membrane integrity by ensuring asymmetric distribution of phospholipids in the canicular membrane (PubMed:21820390). Thus may have a role in the regulation of bile acids transport into the canaliculus, uptake of bile acids from intestinal contents into intestinal mucosa or both and protect hepatocytes from bile salts (PubMed:14976163, PubMed:21820390, PubMed:20126555). Involved in the microvillus formation in polarized epithelial cells; the function seems to be independent from its flippase activity (By similarity). Participates in correct apical membrane localization of CDC42, CFTR and SLC10A2 (PubMed:26416959). Enables CDC42 clustering at the apical membrane during enterocyte polarization through the interaction between CDC42 polybasic region and negatively charged membrane lipids provided by ATP8B1 (PubMed:26416959). Together with TMEM30A is involved in uptake of the synthetic drug alkylphospholipid perifosine (By similarity). Required for the preservation of cochlear hair cells in the inner ear (PubMed:19478059). According PubMed:20852622 is proposed to act as cardiolipin transporter during inflammatory injury; the function is questioned by PubMed:21475228 (PubMed:20852622, PubMed:21475228).|||Cell membrane|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP8B1 and an accessory beta subunit TMEM30A (PubMed:30018401). The flippase ATP8B1:TMEM30A complex can form an intermediate phosphoenzyme in vitro. Also interacts with beta subunit TMEM30B.|||Endoplasmic reticulum|||Golgi apparatus|||Hepatocytes, bile duct, intestinal epithelial cells (cholangiocytes and ileocytes), and pancreatic acinar cells.|||Mice have unimpaired bile secretion, and no liver damage, but show mild abnormalities including depressed weight at weaning and elevated serum bile salt levels. Do not suffer from jaundice or diarrhea and have normal serum bilirubin levels and normal liver enzyme activities, except for mildly elevated serum AST (aspartate aminotransferase) activity. Display unimpaired transhepatic bile salt transport and are resistant to bile salt-induced cholestasis. Upon bile salt feeding, demonstrate serum bile salt accumulation, hepatic injury and expansion of the systemic bile salt pool and this failure of bile salt homeostasis occurs in the absence of any defect in hepatic bile secretion (PubMed:14976163). Mutant mice with B6 background show greater abnormalities than 129 and/or F1 background ones. Pups of B6 background gain less weight. In adult B6 background has lower serum cholesterol levels, higher serum alkaline phosphatase levels, and larger livers. After challenge with cholate-supplemented diet, these mice exhibit higher serum alkaline phosphatase and bilirubin levels, greater weight loss and larger livers (PubMed:20126555).|||stereocilium http://togogenome.org/gene/10090:Tiparp ^@ http://purl.uniprot.org/uniprot/Q8C1B2 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate, aspartate and cysteine residues on target proteins (By similarity). Acts as a negative regulator of AHR by mediating mono-ADP-ribosylation of AHR, leading to inhibit transcription activator activity of AHR (Probable).|||Auto-mono-ADP-ribosylated.|||Belongs to the ARTD/PARP family.|||By 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is a by-product of industrial processes and an important environmental contaminant (PubMed:11716501, PubMed:12147270). This induction is concentration and time-dependent and is mediated through an aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocation (Arnt) signal transduction (PubMed:11716501, PubMed:12147270). Superinduced by cycloheximide and by inhibitors of the 26S proteasome (PubMed:11716501, PubMed:12147270).|||Interacts with AHR.|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Cd209d ^@ http://purl.uniprot.org/uniprot/Q91ZW8 ^@ Caution|||Function|||Subcellular Location Annotation ^@ In mouse, 5 genes homologous to human CD209/DC-SIGN and CD209L/DC-SIGNR have been identified.|||Membrane|||Probable pathogen-recognition receptor. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. May recognize in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens. http://togogenome.org/gene/10090:Trim56 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Q6|||http://purl.uniprot.org/uniprot/Q80VI1 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||By interferon.|||Cytoplasm|||E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity by mediating ubiquitination of CGAS and STING1 (PubMed:21074459, PubMed:29426904). In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets STING1 to 'Lys-63'-linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta (PubMed:21074459). Also mediates monoubiquitination of CGAS, thereby promoting CGAS oligomerization and subsequent activation (PubMed:29426904). Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling (By similarity). Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES (By similarity).|||High susceptibility to DNA virus infection, such as lethal herpes simplex virus-1 (HSV-1) (PubMed:29426904). Cells are defective in CGAS-mediated type I interferon IFN-beta production upon HSV-1 infection (PubMed:29426904). No susceptibility to RNA virus infection, such as influenza A virus (PubMed:29426904). No visible phenotype in normal conditions (PubMed:29426904).|||Interacts with STING1 (PubMed:21074459). Interacts with TICAM1 (By similarity). http://togogenome.org/gene/10090:Cog3 ^@ http://purl.uniprot.org/uniprot/E9QL65|||http://purl.uniprot.org/uniprot/Q3USH9 ^@ Function|||Similarity ^@ Belongs to the COG3 family.|||Involved in ER-Golgi transport. http://togogenome.org/gene/10090:Fam171a2 ^@ http://purl.uniprot.org/uniprot/A2A699 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM171 family.|||Membrane http://togogenome.org/gene/10090:B4galt2 ^@ http://purl.uniprot.org/uniprot/B1ASJ2|||http://purl.uniprot.org/uniprot/Q9Z2Y2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 7 family.|||Golgi apparatus membrane|||Golgi stack membrane|||Membrane|||Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.|||Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids. Can produce lactose (By similarity). http://togogenome.org/gene/10090:Onecut2 ^@ http://purl.uniprot.org/uniprot/Q6XBJ3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the CUT homeobox family.|||It is uncertain whether Met-1 or Met-20 is the initiator.|||Nucleus|||Transcriptional activator. Activates the transcription of a number of liver genes such as HNF3B (By similarity). http://togogenome.org/gene/10090:Ly6h ^@ http://purl.uniprot.org/uniprot/Q9WUC3 ^@ Caution|||Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Believed to act as modulator of nicotinic acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-3:beta-4-containing nAChRs maximum response. In vitro inhibits alpha-3:beta-4-containing nAChRs maximum response (PubMed:26276394). May play a role in the intracellular trafficking of alpha-7-containing nAChRs and may inhibit their expression at the cell surface (PubMed:25716842). Seems to inhibit alpha-7/CHRNA7 signaling in hippocampal neurons (By similarity).|||Cell membrane|||Expression increases during embryonic development.|||Interacts with CHRNA4 and CHRNA7.|||It is uncertain whether Met-1 or Met-6 is the initiator.|||Strongly expressed in brain, also found in lower levels in eye and reproductive tissues. http://togogenome.org/gene/10090:Klkb1 ^@ http://purl.uniprot.org/uniprot/P26262 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase S1 family. Plasma kallikrein subfamily.|||Forms a heterodimer with SERPINA5. The zymogen is activated by factor XIIa, which cleaves the molecule into a light chain, which contains the active site, and a heavy chain, which associates with HMW kininogen. These chains are linked by one or more disulfide bonds (By similarity).|||Inhibited by SERPINA5.|||Secreted|||The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin. http://togogenome.org/gene/10090:Nqo1 ^@ http://purl.uniprot.org/uniprot/Q542Y0|||http://purl.uniprot.org/uniprot/Q64669 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NAD(P)H dehydrogenase (quinone) family.|||By polycyclic hydrocarbons such as dioxin (Governed by the aromatic hydrocarbon-responsive (AH) locus).|||Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (PubMed:8999809) (By similarity). Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (By similarity). Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (By similarity). Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (By similarity).|||Homodimer (PubMed:10706635). Interacts with PDLIM4 isoform 2; this interaction stabilizes PDLIM4 isoform 2 in response to oxidative stress and protects it from ubiquitin-independent degradation by the core 20S proteasome (By similarity). Interacts with TP73 (via SAM domain); this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity). Interacts with TP53; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity).|||cytosol http://togogenome.org/gene/10090:Rad51c ^@ http://purl.uniprot.org/uniprot/Q924H5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the RecA family. RAD51 subfamily.|||Cytoplasm|||Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis.|||Expressed in embryos at various developmental stages. The expression is found to be higher between 11 and 15 days of gestation compared to day 7 or 17.|||Expressed in the heart, brain, spleen, lung, liver, kidney and testis but not detected in skeletal muscle.|||Mitochondrion|||Nucleus|||Part of the RAD51 paralog protein complexes BCDX2 and CX3; the complexes have a ring-like structure arranged into a flat disc around a central channel (By similarity). The BCDX2 complex consits of RAD51B, RAD51C, RAD51D and XRCC2; the CX3 complex consists of RAD51C and XRCC3 (By similarity). The BCDX2 subcomplex RAD51B:RAD51C interacts with RAD51 (By similarity). Interacts with SWSAP1; involved in homologous recombination repair (By similarity). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (By similarity). Interacts with HELQ (PubMed:24005329).|||perinuclear region http://togogenome.org/gene/10090:Prdm6 ^@ http://purl.uniprot.org/uniprot/Q3UZD5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Expressed in a variety of smooth muscle-containing tissues and displays especially robust expression in the cardiac outflow tract and descending aorta during embryogenesis. Also enriched in vascular precursors during development.|||Highly expressed in ductus arteriosus prenatally, expression declines rapildy after birth.|||Interacts with HDAC1, HDAC2, HDAC3, CBX1 and EP300.|||Nucleus|||Putative histone methyltransferase that acts as a transcriptional repressor of smooth muscle gene expression (PubMed:16537907, PubMed:17662997). Promotes the transition from differentiated to proliferative smooth muscle by suppressing differentiation and maintaining the proliferative potential of vascular smooth muscle cells (PubMed:27181681, PubMed:16537907, PubMed:17662997). Also plays a role in endothelial cells by inhibiting endothelial cell proliferation, survival and differentiation. It is unclear whether it has histone methyltransferase activity in vivo. According to some authors, it does not act as a histone methyltransferase by itself and represses transcription by recruiting EHMT2/G9a (PubMed:16537907). According to others, it possesses histone methyltransferase activity when associated with other proteins and specifically methylates 'Lys-20' of histone H4 in vitro. 'Lys-20' methylation represents a specific tag for epigenetic transcriptional repression (PubMed:17662997). http://togogenome.org/gene/10090:Skil ^@ http://purl.uniprot.org/uniprot/D3Z7C5|||http://purl.uniprot.org/uniprot/Q3TB81|||http://purl.uniprot.org/uniprot/Q60665 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the SKI family.|||Interacts with CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with SMAD2, SMAD3 and RNF111. Interacts with WWP1 (By similarity).|||May have regulatory role in cell division or differentiation in response to extracellular signals.|||Ubiquitinated by RNF111 and ARK2C, promoting proteasomal degradation, leading to enhance the BMP-Smad signaling. http://togogenome.org/gene/10090:Ppfia4 ^@ http://purl.uniprot.org/uniprot/B8QI36 ^@ Similarity ^@ Belongs to the liprin family. Liprin-alpha subfamily. http://togogenome.org/gene/10090:Itpripl1 ^@ http://purl.uniprot.org/uniprot/A2ASA8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the ITPRIP family.|||Membrane http://togogenome.org/gene/10090:Cilp ^@ http://purl.uniprot.org/uniprot/A0A0R4J0F8|||http://purl.uniprot.org/uniprot/Q66K08 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.|||Detected in articular cartilage from 8 weeks of age, but not at earlier stages (at protein level).|||Expressed in articular and meniscal cartilage (at protein level). Primarily localizes to the superficial and intermediate zones of articular cartilage (at protein level).|||Monomer. Interacts with TGFB1 (By similarity).|||Probably plays a role in cartilage scaffolding. May act by antagonizing TGF-beta1 (TGFB1) and IGF1 functions. Has the ability to suppress IGF1-induced proliferation and sulfated proteoglycan synthesis, and inhibits ligand-induced IGF1R autophosphorylation. May inhibit TGFB1-mediated induction of cartilage matrix genes via its interaction with TGFB1. Overexpression may lead to impair chondrocyte growth and matrix repair and indirectly promote inorganic pyrophosphate (PPi) supersaturation in aging and osteoarthritis cartilage (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Vmn1r12 ^@ http://purl.uniprot.org/uniprot/G5E8G1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ptprd ^@ http://purl.uniprot.org/uniprot/B9EJA3|||http://purl.uniprot.org/uniprot/Q64487 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A cleavage occurs, separating the extracellular domain from the transmembrane segment. This process called 'ectodomain shedding' is thought to be involved in receptor desensitization, signal transduction and/or membrane localization (By similarity).|||Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.|||Brain, kidney, heart, and some B-cell lines.|||Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically (PubMed:25908590). Involved in pre-synaptic differentiation through interaction with SLITRK2 (PubMed:25989451).|||Interacts with PPFIA1, PPFIA2 and PPFIA3 (By similarity). Interacts (via extracellular domain) with SLITRK4 (via LRR 1 and 2 repeats) (PubMed:25989451). Interacts with SLITRK2; induces presynaptic differentiation (PubMed:25989451). Interacts (via the second immunoglobilin domain) with IL1RAPL1 (via the first immunoglobilin domain); induces pre- and postsynaptic differentiation of neurons and synapse formation. Isoform G, isoform H, isoform I, isoform J, and isoform K do not interact with IL1RAPL1 (PubMed:25908590, PubMed:21940441). Interacts (via the third immunoglobilin domain) with IL1RAP (via the first immunoglobilin domain); induces pre- and postsynaptic differentiation of neurons (PubMed:25908590).|||Membrane http://togogenome.org/gene/10090:Lsm3 ^@ http://purl.uniprot.org/uniprot/P62311 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the snRNP Sm proteins family.|||Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome.|||Nucleus|||Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA. http://togogenome.org/gene/10090:Zfp641 ^@ http://purl.uniprot.org/uniprot/Q8BZ34 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Nucleus|||Transcriptional activator. Activates transcriptional activities of SRE and AP-1 (By similarity). http://togogenome.org/gene/10090:Morn3 ^@ http://purl.uniprot.org/uniprot/Q8C5T4 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Assembles a suppression complex (suppresome) by tethering SIRT1 and MDM2 to regulate composite modifications of p53/TP53. Confers both deacetylation-mediated functional inactivation, by SIRT1, and ubiquitination-dependent degradation, by MDM2, of p53/TP53, promoting a proliferative and cell survival behaviors (By similarity). May play a role in the regulation of spermatogenesis (PubMed:25248657).|||Expressed in testis (at protein level).|||In testis, expression is first detected at 30 days after birth. Abundant in the late stage of spermatogenesis. Highly expressed in the spermiogenesis stage, localized in the acrosome in germ cells throughout spermiogenesis, it is also present in the manchette of elongating spermatids.|||Interacts with MEIG1 (PubMed:25248657). Interacts with TP53, MDM2 and SIRT1; the interactions mediate post-transcriptional modifications of TP53 by MDM2 and SIRT1 (By similarity).|||acrosome http://togogenome.org/gene/10090:Rhox3a2 ^@ http://purl.uniprot.org/uniprot/Q4TU90 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Dlx6 ^@ http://purl.uniprot.org/uniprot/P70397 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the distal-less homeobox family.|||Nucleus http://togogenome.org/gene/10090:Dag1 ^@ http://purl.uniprot.org/uniprot/Q544G5|||http://purl.uniprot.org/uniprot/Q62165|||http://purl.uniprot.org/uniprot/Q8BPJ7|||http://purl.uniprot.org/uniprot/Q8CBE6 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autolytic cleavage produces the alpha and beta subunits. In cutaneous cells, as well as in certain pathological conditions, shedding of beta-dystroglycan can occur releasing a peptide of about 30 kDa (By similarity).|||Broadly expressed in late embryonic and early postnatal cerebellar neurons, including premigratory granule neurons of the external granule cell layer, but expression is largely down-regulated. Weak expression in Purkinje cells throughout development. Alpha- and beta-DG proteins are also present on the Bergmann glial scaffolds used by granule cells during early postnatal radial migration. In the peripheral nerve system, expression briefly precedes and parallels myelination. First expressed at 18.5 dpc in spinal roots, dorsal root ganglions and nerve trunks. At P1, at the onset of myelination, expressed in motor roots. At P5 and P15, expression progressively increases in sensory roots and peripheral nerves. Between postnatal 2 weeks and 18 months, localizes at the nodes of Ranvier as well as at the Schwann cell outer membrane.|||Cell membrane|||Detected in brain and kidney (at protein level) (PubMed:16709410). Detected in sciatic nerve (at protein level) (PubMed:11430802). Expressed in neurons and muscle cells (at protein level) (PubMed:25757569). Expressed in a variety of tissues. In brain, expressed in the hippocampal formation, the olfactory bulb, the cerebellum and the thalamus. In the peripheral nerve system, expressed in Schwann cells.|||Extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains, and for certain adenoviruses. Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells. Also acts as a receptor for laminin LAMA5 (By similarity).|||Homozygous null mice embryos exhibit gross developmental abnormalities, beginning around 6.5 days of gestation, in the Reichert's membrane, an extraembryonic basement membrane. In peripheral nerves, ablation of DAG1 from 4 week-old mice causes abnormalities in nerve structure and function including mildly impaired sorting of axons, dysmyelination, axonal loss and aberrant nerve conduction. Laminin-binding is lost and there is disruption of the Schwann cell dystroglycan complex.|||Membrane|||Monomer. Heterodimer of alpha- and beta-dystroglycan subunits which are the central components of the dystrophin-glycoprotein complex. This complex then can form a dystrophin-associated glycoprotein complex (DGC) which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts (via the N-terminal of alphaDAG1) with LARGE1; the interaction enhances laminin binding (By similarity). Interacts with SGCD. Interacts with AGR2 and AGR3. Interacts (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its PPXY motif) with UTRN (via its WWW and ZZ domains); the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its phosphorylated PPXY motif) with the SH2 domain-containing proteins, FYN, CSK, NCK and SHC. Interacts (betaDAG1) with CAV3 (via a central WW-like domain); the interaction disrupts the binding of DMD. BetaDAG1 directly interacts with ANK3, but not with ANK2; this interaction does not interfere with DMD-binding and is required for retention at costameres (By similarity). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (PubMed:11430802). Interacts with POMGNT1 (By similarity).|||N-glycosylated.|||O-glycosylated (PubMed:20044576). POMGNT1 catalyzes the initial addition of N-acetylglucosamine, giving rise to the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety and thus providing the necessary basis for the addition of further carbohydrate moieties. Heavily O-glycosylated comprising of up to two thirds of its mass and the carbohydrate composition differs depending on tissue type. Mucin-type O-glycosylation is important for ligand binding activity. O-mannosylation is found in high abundance in both brain and muscle where the most abundant glycan is Sia-alpha-2-3-Gal-beta-1-4-Glc-NAc-beta-1-2-Man. In muscle, glycosylation on Thr-315, Thr-317, Thr-379 by a phosphorylated O-mannosyl glycan with the structure 2-(N-acetylamido)-2-deoxygalactosyl-beta-1,3-2-(N-acetylamido)-2-deoxyglucosyl-beta-1,4-6-phosphomannose is mediated by like-acetylglucosaminyltransferase (LARGE1) protein amd is required for laminin binding. O-glycosylated in the N-terminal region with a core 1 or possibly core 8 glycan. The brain form displays a unique glycosylation pattern which is absent in other tissues; this form shows enhanced binding to laminin LAMA5 compared to the skeletal muscle form (By similarity).|||Postsynaptic cell membrane|||SRC-mediated phosphorylation of the PPXY motif of the beta subunit recruits SH2 domain-containing proteins, but inhibits binding to WWW domain-containing proteins, DMD and UTRN. This phosphorylation also inhibits nuclear entry (By similarity).|||Synaptic cell membrane|||The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.|||Transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity (By similarity).|||Transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity.|||cytoskeleton|||extracellular space|||nucleoplasm|||sarcolemma http://togogenome.org/gene/10090:Cntfr ^@ http://purl.uniprot.org/uniprot/O88507 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 3 subfamily.|||Binds to CNTF. The alpha subunit provides the receptor specificity (By similarity).|||Cell membrane|||Forms a heterotrimer with LIFR and IL6ST. Interacts with heterodimeric neurotropic cytokine composed of CLCF1/CLC and CRLF1/CLF-1. Either alone or in complex with the heterodimer CLCF1-CRLF1 interacts with SORL1; this interaction may promote internalization and lysosomal degradation.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. http://togogenome.org/gene/10090:Drd2 ^@ http://purl.uniprot.org/uniprot/P61168 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Conditional knockouts in vascular endothelial cells show an increase in activated Vegfr2/Kdr in the retinal hyaloid at P6, and hyaloid vessels continue to persist at P8.|||Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (PubMed:30936473).|||Expressed in retinal hyaloid vessels at postnatal day 6.|||Expressed in the brain stem.|||Expressed in the pituitary gland, stratum, brain stem and cortex.|||Forms homo- and heterooligomers with DRD4 (By similarity). The interaction with DRD4 may modulate agonist-induced downstream signaling (By similarity). Interacts with CADPS and CADPS2 (By similarity). Interacts with GPRASP1, PPP1R9B and CLIC6 (By similarity). Interacts with ARRB2 (By similarity). Interacts with HTR2A (By similarity). Interacts with DRD1 (PubMed:25865831).|||Golgi apparatus membrane|||Interacts with KCNA2.|||Palmitoylated. Palmitoylation which is required for proper localization to the plasma membrane and stability of the receptor could be carried on by ZDHHC4, ZDHHC3 and ZDHHC8. http://togogenome.org/gene/10090:Slc16a5 ^@ http://purl.uniprot.org/uniprot/G5E8K6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Cell membrane|||Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate (By similarity). http://togogenome.org/gene/10090:Marchf5 ^@ http://purl.uniprot.org/uniprot/Q3KNM2 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated leading to degradation.|||Endoplasmic reticulum membrane|||Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1.|||Mitochondrion outer membrane|||Monomer and homodimer. Interacts with MFN1, MFN2, DNM1L and FIS1.|||The RING-CH-type zinc finger domain is required for E3 ligase activity. http://togogenome.org/gene/10090:Vmn2r24 ^@ http://purl.uniprot.org/uniprot/D3YUI0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrap ^@ http://purl.uniprot.org/uniprot/Q9D159 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the MRAP family.|||Cell membrane|||Endoplasmic reticulum membrane|||Expressed during adipocyte differentiation. Expression appears 2 days following induction of adipose conversion, reaching a peak after 6 days.|||Homodimer and heterodimer. Forms antiparallel homodimers and heterodimers with MRAP2. Interacts with MC1R, MC2R, MC3R, MC4R and MC5R (By similarity).|||Largely restricted to fat tissues. Predominantly expressed in mouse epididymal (white adipose tissue) and interscapular (brown adipose tissue) fat pads. Expression is weak or absent in lung, spleen, intestine, kidney, heart and skeletal muscle.|||Modulator of melanocortin receptors (MC1R, MC2R, MC3R, MC4R and MC5R). Acts by increasing ligand-sensitivity of melanocortin receptors and enhancing generation of cAMP by the receptors. Required both for MC2R trafficking to the cell surface of adrenal cells and for signaling in response to corticotropin (ACTH). May be involved in the intracellular trafficking pathways in adipocyte cells (By similarity). http://togogenome.org/gene/10090:Degs2 ^@ http://purl.uniprot.org/uniprot/Q8R2F2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.|||Bifunctional enzyme which acts as both a sphingolipid delta(4)-desaturase and a sphingolipid C4-monooxygenase.|||Endoplasmic reticulum membrane|||Highly expressed in intestinal crypt cells and adjacent epithelial cells (at protein level). http://togogenome.org/gene/10090:Smr2l ^@ http://purl.uniprot.org/uniprot/E9Q079 ^@ Function|||Subcellular Location Annotation ^@ May play a role in protection or detoxification.|||Secreted http://togogenome.org/gene/10090:Itgb7 ^@ http://purl.uniprot.org/uniprot/P26011 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the integrin beta chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. ITGB7/beta-7 associates with either ITGA4/alpha-4 or ITGAE/alpha-E. Integrin ITGA4/ITGB7 interacts with MADCAM1. Integrin ITGA4/ITGB7 interacts with VCAM1 and fibronectin. Interacts with FLNA (via filamin repeats 4, 9, 12, 17, 19, 21, and 23).|||Integrin ITGA4/ITGB7 (alpha-4/beta-7) (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin ITGA4/ITGB7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and fibronectin, an extracellular matrix component. It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin. Interactions involve the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin. Integrin ITGAE/ITGB7 (alpha-E/beta-7, HML-1) is a receptor for E-cadherin.|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site. The MIDAS site is required for both rolling and adhesion. The ADMIDAS site is required for rolling and mediates the negative regulatory effects of higher Ca(2+) concentration on ligand binding. The LIMBS site is required for adhesion and mediates the positive regulatory effects of low Ca(2+) concentrations on ligand binding. http://togogenome.org/gene/10090:Mrgpra3 ^@ http://purl.uniprot.org/uniprot/H3BKL3|||http://purl.uniprot.org/uniprot/Q91WW3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Expressed exclusively in dorsal root ganglia and nodose ganglia. Expressed in a subset of sensory neurons that includes nociceptors. Expressed in the subclass of non-peptidergic sensory neurons that are IB4(+) and VR1(-).|||Membrane|||Orphan receptor. May be a receptor for RFamide-family neuropeptides such as NPFF and NPAF, which are analgesic in vivo. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). Activated by the antimalarial drug chloroquine. Mediates chloroquine-induced itch, in a histamine-independent manner. http://togogenome.org/gene/10090:Ptcra ^@ http://purl.uniprot.org/uniprot/P0C6B2 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with RHBDD1 (By similarity). Heterodimer with TCRB; disulfide linked. This heterodimer assembles with CD3 proteins into a signaling-competent pre-T-cell receptor complex.|||Isoform 1 is expressed at higher levels than isoform 2 in the thymus while only isoform 2 is expressed in polyclonal beta-only cells. Isoform 1 shows a predominant expression in immature thymocytes.|||Membrane|||The pre-T-cell receptor complex (composed of PTCRA, TCRB and the CD3 complex) regulates early T-cell development. Isoform 1 acts to retain most TCRB intracellularly, while isoform 2 permits higher levels of cell surface TCRB expression and facilitates signaling from the CD3-TCRB complex. http://togogenome.org/gene/10090:Ndufs8 ^@ http://purl.uniprot.org/uniprot/Q3UY05|||http://purl.uniprot.org/uniprot/Q5M9P5|||http://purl.uniprot.org/uniprot/Q8K3J1 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I 23 kDa subunit family.|||Binds 2 [4Fe-4S] cluster.|||Complex I is composed of 45 different subunits (By similarity). This is a component of the iron-sulfur (IP) fragment of the enzyme (By similarity). Interacts with RAB5IF (PubMed:31536960).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (By similarity). Essential for the catalytic activity and assembly of complex I (By similarity).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Edc4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J1Q0|||http://purl.uniprot.org/uniprot/G5E896|||http://purl.uniprot.org/uniprot/Q3UJB9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WD repeat EDC4 family.|||In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro).|||Nucleus|||P-body|||Part of a decapping complex consisting of DCP1A, DCP2, EDC3, EDC4 and probably DDX6. Part of a complex consisting of DCP1A, EDC3, EDC4 and DDX6. Part of a complex consisting of DCP1B, EDC3, EDC4 and DDX6. Interacts with DCP2 (By similarity). Interacts with RC3H1 (PubMed:20639877, PubMed:23583643). Interacts with NBDY (By similarity). Interacts with Tex19.1 and, probably, Tex19.2 (PubMed:28254886). Interacts with LSM14A (By similarity). Interacts with DDX6 (By similarity). http://togogenome.org/gene/10090:Aspa ^@ http://purl.uniprot.org/uniprot/Q8R3P0 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AspA/AstE family. Aspartoacylase subfamily.|||Binds 1 zinc ion per subunit.|||Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter (By similarity).|||Cytoplasm|||Homodimer.|||Nucleus http://togogenome.org/gene/10090:Alg3 ^@ http://purl.uniprot.org/uniprot/Q8K2A8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man5GlcNAc2-PP-Dol.|||Belongs to the glycosyltransferase 58 family.|||Endoplasmic reticulum membrane http://togogenome.org/gene/10090:Or8k18 ^@ http://purl.uniprot.org/uniprot/A2ARZ0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gal3st3 ^@ http://purl.uniprot.org/uniprot/P61315 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the galactose-3-O-sulfotransferase family.|||Golgi stack membrane|||Transfers a sulfate to position 3 of non-reducing beta-galactosyl residues in N-glycans and core2-branched O-glycans. Has high activity towards Gal-beta-1,4-GlcNAc, Gal-beta-1,4(Fuc-alpha-1,3)GlcNAc and lower activity towards Gal-beta-1,3(Fuc-alpha-1,4)GlcNAc (By similarity). http://togogenome.org/gene/10090:Acsm1 ^@ http://purl.uniprot.org/uniprot/Q91VA0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ATP-dependent AMP-binding enzyme family.|||Catalyzes the activation of fatty acids by CoA to produce an acyl-CoA, the first step in fatty acid metabolism (PubMed:11470804, PubMed:12709059). Capable of activating medium-chain fatty acids (e.g. butyric (C4) to decanoic (C10) acids), and certain carboxylate-containing xenobiotics, e.g. benzoate (PubMed:11470804, PubMed:12709059). Also catalyzes the activation of lipoate to lipoyl-nucleoside monophosphate (By similarity). Activates lipoate with GTP at a 1000-fold higher rate than with ATP and activates both (R)- and (S)-lipoate to the respective lipoyl-GMP, with a preference for (R)-lipoate (By similarity).|||Highly expressed in liver and kidney.|||Mitochondrion|||Mitochondrion matrix|||Monomer. http://togogenome.org/gene/10090:Ube3b ^@ http://purl.uniprot.org/uniprot/Q9ES34 ^@ Function|||Tissue Specificity ^@ E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.|||Widely expressed. High expression is observed in developing central nervous system. http://togogenome.org/gene/10090:Asah1 ^@ http://purl.uniprot.org/uniprot/Q78P93|||http://purl.uniprot.org/uniprot/Q9WV54 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the acid ceramidase family.|||Expression is detected from 7 dpc to 17 dpc, during fetal development.|||Heterodimer.|||Heterodimer; disulfide-linked. The heterodimer is composed of the disulfide-linked alpha and beta chains produced by autocatalytic cleavage of the precursor.|||Lethal for homozygous knockout embryos (PubMed:11829492). Heterozygous knockout mice are viable, grow normally and do not present overt clinical phenotype (PubMed:11829492). However, they progressively develop lipid storage-associated phenotypes, with an elevation of ceramides levels and an accumulation of lipid-laden inclusions in liver, more specifically in Kupffer cells, and other tissues (PubMed:11829492). Associated with the accumulation of ceramides, a depression-like phenotype is observed for heterozygous knockout mice (PubMed:23770692).|||Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH (PubMed:9653654, PubMed:11829492). Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation (PubMed:9653654). Has a higher catalytic efficiency towards C12-ceramides versus other ceramides (By similarity). Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine (By similarity). For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used (By similarity). Has also an N-acylethanolamine hydrolase activity (By similarity). By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes (By similarity). Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis (PubMed:10974027). By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis (By similarity).|||Lysosome|||N-glycosylated.|||Proteolytically cleaved into two chains alpha and beta that remain associated via a disulfide bond. Cleavage gives rise to a conformation change that activates the enzyme. The same catalytic Cys residue mediates the autoproteolytic cleavage and subsequent hydrolysis of lipid substrates. The beta chain may undergo an additional C-terminal processing.|||Secreted|||Widely expressed. http://togogenome.org/gene/10090:Tatdn3 ^@ http://purl.uniprot.org/uniprot/D3Z0V5|||http://purl.uniprot.org/uniprot/E9QL22|||http://purl.uniprot.org/uniprot/Q3U1C6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.|||Binds 2 divalent metal cations per subunit.|||Nucleus|||Putative deoxyribonuclease. http://togogenome.org/gene/10090:Gsta3 ^@ http://purl.uniprot.org/uniprot/P30115 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Alpha family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively (By similarity). Has a high catalytic activity for aflatoxin B1-8,9 epoxide (PubMed:1637297).|||Cytoplasm|||Homodimer. http://togogenome.org/gene/10090:Pcmtd2 ^@ http://purl.uniprot.org/uniprot/B0R0C7|||http://purl.uniprot.org/uniprot/Q8BHD8 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Although the active site residue Ser is conserved, appears to lack catalytic activity in vitro.|||At its N-terminus, contains L-isoaspartate and S-adenosylmethionine (AdoMet) binding motifs. Also contains an extended SOCS box motif, where the Cul-box is separated from the BC-box by ~90 residues, within its C-terminus.|||Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.|||Cytoplasm|||May act as a substrate recognition component of an ECS (Elongin BC-CUL5-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. May bind to the methyltransferase cofactor S-adenosylmethionine (AdoMet) via the N-terminal AdoMet binding motif, but probably does not display methyltransferase activity. http://togogenome.org/gene/10090:Nudt11 ^@ http://purl.uniprot.org/uniprot/P0C027|||http://purl.uniprot.org/uniprot/P0C028 ^@ Cofactor|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Nudix hydrolase family. DIPP subfamily.|||Binds 3 Mg(2+) or Mn(2+) ions per subunit. Mn(2+) may be the true cofactor in vivo.|||Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate; however, the relevance of such activity in vivo remains unclear.|||Cytoplasm|||Mainly expressed in testis, liver kidney and, at lower level, in heart, brain, spleen, lung and skeletal muscle.|||Nudt10 and Nudt11 code for identical proteins, which gives their indidual characterization difficult. Thus, most experiments do not discriminate between the 2 proteins.|||Predominantly expressed in brain and is weakly or not expressed in other tissues. http://togogenome.org/gene/10090:Rsph3b ^@ http://purl.uniprot.org/uniprot/Q9DA80 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the flagellar radial spoke RSP3 family.|||Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3B, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB (PubMed:34871179). Interacts with IQUB (By similarity). Interacts with phosphorylated MAPK1 (By similarity). Interacts with MEK1 (By similarity). Interacts with PKA regulatory subunits PRKAR1A and PRKAR1B (By similarity). Interacts with RSPH1 (PubMed:34871179). Interacts with RSPH4A (PubMed:34871179). Interacts with RSPH6A (PubMed:34871179). Interacts with RSPH9 (PubMed:34871179).|||Expressed in ependymal cells (at protein level).|||Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (PubMed:34871179). Functions as a protein kinase A-anchoring protein that scaffolds the cAMP-dependent protein kinase holoenzyme. May serve as a point of convergence for MAPK and PKA signaling in cilia (By similarity).|||cilium axoneme|||flagellum axoneme http://togogenome.org/gene/10090:Vps37d ^@ http://purl.uniprot.org/uniprot/Q810I0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS37 family.|||Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with TSG101 and MVB12A. Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and UBAP1 in a 1:1:1:1 stoichiometry (By similarity).|||Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in cell growth and differentiation (By similarity).|||Late endosome membrane http://togogenome.org/gene/10090:Cul7 ^@ http://purl.uniprot.org/uniprot/A9C491|||http://purl.uniprot.org/uniprot/Q8VE73 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the cullin family.|||Component of the 3M complex, composed of core components CUL7, CCDC8 and OBSL1. Part of a Cul7-RING complex consisting of CUL7, RBX1, SKP1 and FBXW8. Interacts with a complex of SKP1 and FBXW8, but not with SKP1 alone. Interacts with CUL9; leading to inhibit CUL9 activity. Interacts with FBXW8; interaction is mutually exclusive of binding to CUL9 or p53/TP53. Interacts with p53/TP53; the interaction preferentially involves tetrameric and dimeric p53/TP53. The CUL7-CUL9 heterodimer seems to interact specifically with p53/TP53. Interacts with OBSL1 (By similarity). Interacts with CUL1; the interactions seems to be mediated by FBXW8. Interacts (as part of the 3M complex) with HDAC4 and HDAC5; it is negatively regulated by ANKRA2 (By similarity).|||Core component of the 3M and Cul7-RING(FBXW8) complexes, which mediates the ubiquitination of target proteins. Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer. Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5. Core component of a Cul7-RING ubiquitin-protein ligase with FBXW8, which mediates ubiquitination and consequent degradation of target proteins such as GORASP1, IRS1 and MAP4K1/HPK1. Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain. Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation. Acts as a regulator in trophoblast cell epithelial-mesenchymal transition and placental development. Does not promote polyubiquitination and proteasomal degradation of p53/TP53. While the Cul7-RING(FBXW8) and the 3M complexes are associated and involved in common processes, CUL7 and the Cul7-RING(FBXW8) complex may be have additional functions (By similarity). Probably plays a role in the degradation of proteins involved in endothelial proliferation and/or differentiation.|||Cytoplasm|||Golgi apparatus|||Mice are neonatal lethal and show vascular defects in both the embryo and the placenta.|||centrosome|||perinuclear region http://togogenome.org/gene/10090:Lhfpl7 ^@ http://purl.uniprot.org/uniprot/Q3UUA0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM211 family.|||Membrane http://togogenome.org/gene/10090:Slc25a30 ^@ http://purl.uniprot.org/uniprot/Q9CR58 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antiporter that transports inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate. The sulfate/sulfate exchange is much higher than the phosphate/phosphate and malate/malate exchanges. The transport affinities is higher for sulfate and thiosulfate than for any other substrate. May catalyze the export of sulfite and thiosulfate (the hydrogen sulfide degradation products) from the mitochondria, thereby modulating the level of the hydrogen sulfide. Also may mediate a very low unidirectional transport of sulfate, phosphate and (S)-malate.|||Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Interacts with VDAC1.|||Mitochondrion inner membrane|||Present in kidney (at protein level). Expressed predominantly within the kidney cortex in the proximal and distal tubules and at lower levels in the testis and white adipose tissue.|||Up-regulated during fasting and in the regenerative phase following renal tubular injury. http://togogenome.org/gene/10090:Herc2 ^@ http://purl.uniprot.org/uniprot/Q4U2R1 ^@ Disease Annotation|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Defects in Herc2 are the cause of the runty, jerky, sterile phenotype (rjs), also known as the juvenile development and fertility phenotype (jfd2), which is characterized by reduced size, jerky gait, fertility problems including spermatocyte and oocyte abnormalities, defective maternal behavior and reduced lifespan with juvenile lethality.|||E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. Modulates also iron metabolism by regulating the basal turnover of FBXL5.|||Highest levels are found in brain and testis with lower levels in heart, lung, liver, skeletal muscle and kidney. Little expression detected in spleen.|||Interacts (when phosphorylated at Thr-4829 and sumoylated) with RNF8 (via FHA domain); this interaction increases after ionising radiation (IR) treatment. Interacts with XPA. Interacts with NEURL4. Via its interaction with NEURL4, may indirectly interact with CCP110 and CEP97.|||Nucleus|||Phosphorylation at Thr-4829 is required for interaction with RNF8.|||Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs), promoting the interaction with RNF8.|||The RCC1 repeats are grouped into three seven-bladed beta-propeller regions.|||The ZZ-type zinc finger mediates binding to SUMO1, and at low level SUMO2.|||centriole http://togogenome.org/gene/10090:Xntrpc ^@ http://purl.uniprot.org/uniprot/F8VQM8 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Taf4 ^@ http://purl.uniprot.org/uniprot/E9QAP7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the TAF4 family.|||Nucleus http://togogenome.org/gene/10090:Rhox9 ^@ http://purl.uniprot.org/uniprot/Q9EQM5 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Slc8a3 ^@ http://purl.uniprot.org/uniprot/E9PX50|||http://purl.uniprot.org/uniprot/Q3UTP5|||http://purl.uniprot.org/uniprot/Q8BXN1|||http://purl.uniprot.org/uniprot/S4R2P9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.|||Calcium transport is stimulated by cytoplasmic Ca(2+) and is inhibited by Na(+). Isoform 1 is more sensitive to stimulation by Ca(2+) than isoform 2. Isoform 2 is more sensitive to inactivation by Na(+).|||Cell junction|||Cell membrane|||Detected in gray and white matter in the spinal cord (PubMed:21959935). Detected in hippocampus neurons (PubMed:21593315). Detected in brain cortex neurons (PubMed:24101730). Detected in skeletal muscle (at protein level) (PubMed:14722618). Isoform 1 and isoform 2 are highly expressed in brain; levels are higher for isoform 2 (PubMed:24616101). Isoform 1 and isoform 2 are detected in soleus muscle; levels are higher for isoform 1 (PubMed:24616101). Detected in gastrocnemius muscle (PubMed:14722618).|||Down-regulated by hypoxia combined with glucose deprivation (at protein level).|||Endoplasmic reticulum membrane|||Interacts with AKAP1.|||Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes. Contributes to cellular Ca(2+) homeostasis in excitable cells, both in muscle and in brain (PubMed:14722618, PubMed:21593315). In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A3 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline (PubMed:14722618, PubMed:21593315). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle (PubMed:14722618). In neurons, contributes to the rapid decrease of cytoplasmic Ca(2+) levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory (PubMed:21593315). Required for normal oligodendrocyte differentiation and for normal myelination (PubMed:21959935). Mediates Ca(2+) efflux from mitochondria and contributes to mitochondrial Ca(2+) ion homeostasis (PubMed:24616101). Isoform 1 displays higher calcium exchanger activity than isoform 2, probably because isoform 1 has a lower threshold for activation by cytoplasmic Ca(2+) (PubMed:24616101).|||Membrane|||Mice appear grossly normal, are viable and fertile, but display muscle fiber necrosis; this affects less than 10% of all fibers. Muscle fibers from flexor digitorum brevis show lack of calcium exchange activity, and very slow return of cytoplasmic Ca(2+) to baseline levels after stimulation with caffeine, a stimulus that triggers release of Ca(2+) stores from the sarcoplasmic reticulum. Mutant mice display decreased endurance and perform poorly on the rota-rod test or when hanging from a taut wire, indicating poor coordination and increased fatigue (PubMed:14722618). Mutant mice display increased cytoplasmic Ca(2+) levels and increased delays in the decrease of cytoplasmic Ca(2+) back to baseline levels after stimulation of hippocampus neurons (PubMed:21593315). They show impaired synaptic transmisison, impaired long-term potentiation, impaired learning and memory (PubMed:21593315). Besides, mutant mice display a decreased size of the spinal cord, decreased myelination, decreased numbers of oligodendrocytes and increased numbers of oligodendrocyte precursor cells (PubMed:21959935).|||Mitochondrion outer membrane|||Perikaryon|||The cytoplasmic Calx-beta domains bind the regulatory Ca(2+). The first Calx-beta domain can bind up to four Ca(2+) ions. The second domain can bind another two Ca(2+) ions that are essential for calcium-regulated ion exchange.|||dendrite|||dendritic spine|||perinuclear region|||sarcolemma|||sarcoplasm http://togogenome.org/gene/10090:Gpbp1l1 ^@ http://purl.uniprot.org/uniprot/Q6NZP2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the vasculin family.|||Nucleus|||Possible transcription factor. http://togogenome.org/gene/10090:Prss52 ^@ http://purl.uniprot.org/uniprot/Q9D9M0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family.|||Membrane|||Probable serine protease. http://togogenome.org/gene/10090:Gmip ^@ http://purl.uniprot.org/uniprot/Q6PGG2 ^@ Function|||Subunit ^@ Interacts with GEM through its N-terminal.|||Stimulates, in vitro and in vivo, the GTPase activity of RhoA. http://togogenome.org/gene/10090:Tmem127 ^@ http://purl.uniprot.org/uniprot/Q8BGP5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM127 family.|||Cell membrane|||Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1. May act as a tumor suppressor.|||Cytoplasm http://togogenome.org/gene/10090:Ttr ^@ http://purl.uniprot.org/uniprot/P07309|||http://purl.uniprot.org/uniprot/Q5M9K1 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transthyretin family.|||Detected in plasma (at protein level). Detected in liver.|||Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with RBP4 (By similarity).|||Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with RBP4.|||Secreted|||Sulfonation of the reactive cysteine Cys-30 enhances the stability of the native conformation of TTR, avoiding misassembly of the protein leading to amyloid formation.|||The mouse protein shows increased stability and much reduced propensity to form amyloid fibrils, compared to the human protein.|||Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain. http://togogenome.org/gene/10090:Pycr1 ^@ http://purl.uniprot.org/uniprot/Q3UTR5|||http://purl.uniprot.org/uniprot/Q922W5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pyrroline-5-carboxylate reductase family.|||Highly expressed in osteoblasts and skin.|||Homodecamer; composed of 5 homodimers. Interacts with LTO1.|||Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.|||Mitochondrion http://togogenome.org/gene/10090:Tmem119 ^@ http://purl.uniprot.org/uniprot/Q8R138 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ By parathyroid hormone (PTH) in osteoblasts (at protein level).|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Expressed in spermatocytes and spermatids in the developing testis (at protein level). Expressed in the brain, heart, lung, spleen, skeletal muscle, ovary, testis and epididymis (PubMed:26207632). Predominantly expressed in osteoblasts (PubMed:20025746).|||Highly expressed in early and late stage osteoblasts of developing embryos (at protein level).|||Interacts with SMAD1, SMAD5 and RUNX2.|||Mice show a significant decrease in bone formation and bone mineralization and the mineralization defect is independent of calcium and phosphate metabolisms. Testis is smaller, sperm number is significantly decreased and testicular differentiation is perturbed (PubMed:26207632). Significantly reduced cortical thickness in the mid-shaft of the femur at postnatal day 14 (P14), and progressive bone hypoplasia after 8 weeks (PubMed:22416756).|||Plays an important role in bone formation and normal bone mineralization (PubMed:26207632, PubMed:22416756, PubMed:20025746). Promotes the differentiation of myoblasts into osteoblasts (PubMed:22416756, PubMed:20025746, PubMed:22579779). May induce the commitment and differentiation of myoblasts into osteoblasts through an enhancement of BMP2 production and interaction with the BMP-RUNX2 pathway (PubMed:21239498, PubMed:22579779). Up-regulates the expression of ATF4 which plays a central role in osteoblast differentiation (PubMed:24362451). Essential for normal spermatogenesis and late testicular differentiation (PubMed:26207632). http://togogenome.org/gene/10090:Blk ^@ http://purl.uniprot.org/uniprot/P16277 ^@ Activity Regulation|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Antibody-mediated surface engagement of the B-cell antigen receptor (BCR) which results in the phosphorylation of BLK on tyrosine residues, stimulates the enzymatic activity.|||Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.|||Cell membrane|||Expressed in immature Vgamma2 gamma-delta T-cells (at protein level) (PubMed:23562159). Expressed in the B-cell lineage (PubMed:2404338, PubMed:1537861).|||Expression increases during B-cell differentiation and is under the control of the B-cell specific transcription factors PAX5 and NF-kappa-B.|||Interacts with CBL (via SH2 domain) (By similarity). Interacts with CD79A and CD79B (via SH2 domain).|||Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:9636152, PubMed:14662906, PubMed:12563261). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (PubMed:2404338, PubMed:7690139, PubMed:7608542, PubMed:14662906, PubMed:12563261). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (PubMed:7592958, PubMed:9177269). Phosphorylates also the immunoglobulin G receptor FCGR2 (By similarity). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (PubMed:14662906, PubMed:12563261). Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (PubMed:7565679). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (By similarity). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (By similarity).|||Phosphorylated on tyrosine residues after antibody-mediated surface engagement of the B-cell antigen receptor (BCR).|||Ubiquitination of activated BLK by the UBE3A ubiquitin protein ligase leads to its degradation by the ubiquitin-proteasome pathway. http://togogenome.org/gene/10090:Hsp90aa1 ^@ http://purl.uniprot.org/uniprot/P07901|||http://purl.uniprot.org/uniprot/Q80Y52 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the heat shock protein 90 family.|||Cell membrane|||Cytoplasm|||Homodimer (PubMed:8289821). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:9195923, PubMed:11278753, PubMed:11751894). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (By similarity). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (By similarity). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (By similarity). Interacts with CHORDC1 and DNAJC7 (By similarity). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (By similarity). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (By similarity). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (By similarity). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (By similarity). May interact with NWD1 (By similarity). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (By similarity). Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (By similarity). Interacts with HSP70, STIP1 and PTGES3 (By similarity). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase (By similarity). Interacts with SGTA (via TPR repeats) (By similarity). Interacts with TTC1 (via TPR repeats) (By similarity). Interacts with HSF1 in an ATP-dependent manner (By similarity). Interacts with MET; the interaction suppresses MET kinase activity (By similarity). Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (By similarity). Interacts with HIF1A, KEAP1 and RHOBTB2 (By similarity). Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (By similarity). Interacts with STUB1 and SMAD3 (By similarity). Interacts with HSP90AB1; interaction is constitutive (By similarity). Interacts with HECTD1 (via N-terminus) (PubMed:22431752). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (PubMed:27686098). Interacts with NLPR12. Interacts with PDCL3 (PubMed:27496612). Interacts with TOMM70; the interaction is required for preprotein mitochondrial import. Interacts with TOMM70, IRF3 and TBK1; the interactions are direct and mediate the association of TOMM70 with IRF3 and TBK1 (By similarity). Forms a complex with ASL, ASS1 and NOS2; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.|||ISGylated.|||In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (By similarity). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (By similarity). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (By similarity). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (By similarity).|||Melanosome|||Mitochondrion|||Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response.|||Nucleus|||S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.|||The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.|||Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways. http://togogenome.org/gene/10090:Sh3bp1 ^@ http://purl.uniprot.org/uniprot/P55194 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell projection|||Expressed in all tissues examined. Highest levels found in spleen and brain, lowest in heart and liver.|||GTPase activating protein (GAP) which specifically converts GTP-bound Rho-type GTPases including RAC1 and CDC42 in their inactive GDP-bound form (PubMed:7621827). By specifically inactivating RAC1 at the leading edge of migrating cells, it regulates the spatiotemporal organization of cell protrusions which is important for proper cell migration. Also negatively regulates CDC42 in the process of actin remodeling and the formation of epithelial cell junctions. Through its GAP activity toward RAC1 and/or CDC42 plays a specific role in phagocytosis of large particles. Specifically recruited by a PI3 kinase/PI3K-dependent mechanism to sites of large particles engagement, inactivates RAC1 and/or CDC42 allowing the reorganization of the underlying actin cytoskeleton required for engulfment. It also plays a role in angiogenesis and the process of repulsive guidance as part of a semaphorin-plexin signaling pathway. Following the binding of PLXND1 to extracellular SEMA3E it dissociates from PLXND1 and inactivates RAC1, inducing the intracellular reorganization of the actin cytoskeleton and the collapse of cells (By similarity).|||Interacts with RAC1 (PubMed:10508610). Interacts with the exocyst via EXOC4 and EXOC8; required for the localization of both SH3BP1 and the exocyst to the leading edge of migrating cells. Interacts with CD2AP and CGNL1; probably part of a complex at cell junctions. Interacts with CAPZA1; recruits CAPZA1 to forming cell junctions. May interact with AFDN. Interacts with PLXND1; they dissociate upon SEMA3E binding to PLXND1 allowing SH3BP1 to transduce downstream signal through RAC1 inactivation (By similarity). Interacts with ABL1, GRB2 and SRC (via SH3 domain) (PubMed:8438166, PubMed:1379745).|||Nucleus|||The BAR domain mediates interaction with the exocyst components EXOC4 and EXOC8 and is required for the function in cell migration. It also mediates the interaction with PLXND1.|||adherens junction|||cytosol|||phagocytic cup|||tight junction http://togogenome.org/gene/10090:Defb26 ^@ http://purl.uniprot.org/uniprot/Q30KN7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Secreted http://togogenome.org/gene/10090:Fam20a ^@ http://purl.uniprot.org/uniprot/Q8CID3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM20 family.|||By all-trans retinoic acid (atRA) and IL3 in EML cell line.|||Endoplasmic reticulum|||Golgi apparatus|||In EML and MPRO cell lines, low levels in undifferentiated cells. Induced during maturation to promyelocyte stage of neutrophil differentiation. Decreased during neutrophil terminal differentiation.|||In the mammary gland, expressed at higher levels in lactating mice than in virgin mice (PubMed:29858230). Observed throughout the tissues of the mandibular incisor, including the secretory and maturation stage ameloblasts, the suprabasal layers of the gingival epithelium and the odontoblasts. Weak expression in the enamel matrix.|||Interacts with FAM20C; probably forming a heterotetramer of 2 subunits of FAM20A and 2 subunits of FAM20C.|||Mice survive to adulthood and show biomineralization defects such as severe amelogenesis imperfecta (AI). In addition, mice develop disseminated calcifications of muscular arteries and intrapulmonary calcifications, similar to those of fetuin-A (Ahsg) deficient mice, although they are normocalcemic and normophosphatemic, with normal dentin and bone.|||N-glycosylated.|||Pseudokinase that acts as an allosteric activator of the Golgi serine/threonine protein kinase FAM20C and is involved in biomineralization of teeth. Forms a complex with FAM20C and increases the ability of FAM20C to phosphorylate the proteins that form the 'matrix' that guides the deposition of the enamel minerals.|||Secreted http://togogenome.org/gene/10090:Hif1an ^@ http://purl.uniprot.org/uniprot/Q8BLR9 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||Homodimer; homodimerization is essential for catalytic activity. Interacts with VHL and HIF1A. Part of a complex with VHL, HIF1A and HDAC1 or HDAC2 or HDAC3. Interacts with NFKB1 and NFKBIA. Interacts with NOTCH1, NOTCH2 and NOTCH3 but not with NOTCH4. Interacts with ABPA3. Interacts with TNKS2. Interacts with PPP1R12A (By similarity). Interacts with UBE3A (By similarity). Interacts with ASB4. Interacts with ANKS3 (PubMed:25671767). Interacts with NECAB3; the interaction is indirect and seems to be mediated by APBA3 (By similarity).|||Hydroxylates HIF-1 alpha at 'Asn-799' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation (By similarity). Positively regulates ASB4 activity, promoting vascular differentiation.|||Nucleus|||perinuclear region http://togogenome.org/gene/10090:Rnf144a ^@ http://purl.uniprot.org/uniprot/Q925F3 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated.|||Belongs to the RBR family. RNF144 subfamily.|||Cell membrane|||Cytoplasmic vesicle membrane|||E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates the ubiquitination and degradation of the DNA damage kinase PRKDC.|||Interacts with UBE2L3.|||Lacks the His residue in the RING-type domain 2 that is one of the conserved features of the family.|||Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain. http://togogenome.org/gene/10090:Nps ^@ http://purl.uniprot.org/uniprot/P0C0P8 ^@ Function|||Subcellular Location Annotation ^@ May play an important anorexigenic role. Modulates arousal and anxiety as well as increases locomotor activity. Binds to its receptor NPSR1 with nanomolar affinity to increase intracellular calcium concentrations.|||Secreted http://togogenome.org/gene/10090:Scaf1 ^@ http://purl.uniprot.org/uniprot/Q5U4C3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Interacts with POLR2A.|||May function in pre-mRNA splicing.|||Nucleus http://togogenome.org/gene/10090:Metrnl ^@ http://purl.uniprot.org/uniprot/Q8VE43 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the meteorin family.|||Highly expressed in subcutaneous adipose tissue.|||Hormone induced following exercise or cold exposure that promotes energy expenditure. Induced either in the skeletal muscle after exercise or in adipose tissue following cold exposure and is present in the circulation. Able to stimulate energy expenditure associated with the browning of the white fat depots and improves glucose tolerance. Does not promote an increase in a thermogenic gene program via direct action on adipocytes, but acts by stimulating several immune cell subtypes to enter the adipose tissue and activate their prothermogenic actions. Stimulates an eosinophil-dependent increase in IL4 expression and promotes alternative activation of adipose tissue macrophages, which are required for the increased expression of the thermogenic and anti-inflammatory gene programs in fat. Required for some cold-induced thermogenic responses, suggesting a role in metabolic adaptations to cold temperatures.|||N-glycosylated.|||Secreted|||Up-regulated during adipogenesis and obesity. Induced either in muscle after exercise or in adipose tissue upon cold exposure (at protein level). Expression is induced by Ppargc1a isoform 4 (PubMed:24906147). http://togogenome.org/gene/10090:Slc17a9 ^@ http://purl.uniprot.org/uniprot/Q8VCL5 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activity is chloride-dependent.|||Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.|||In brain, specifically expressed in the medulla and is associated with chromaffin granules (at protein level). Predominantly expressed in adrenal gland, brain and thyroid.|||Lysosome membrane|||Voltage-gated ATP nucleotide uniporter that can also transport the purine nucleotides ADP and GTP. Uses the membrane potential as the driving force to control ATP accumulation in lysosomes and secretory vesicles (PubMed:23876310, PubMed:24962569, PubMed:27477609). By controlling ATP storage in lysosomes, regulates ATP-dependent proteins of these organelles (PubMed:23832620, PubMed:24962569, PubMed:27477609). Also indirectly regulates the exocytosis of ATP through its import into lysosomes in astrocytes and secretory vesicles such as adrenal chromaffin granules, mucin granules and synaptic vesicles (By similarity).|||chromaffin granule membrane|||secretory vesicle membrane http://togogenome.org/gene/10090:Retn ^@ http://purl.uniprot.org/uniprot/Q5BMX4|||http://purl.uniprot.org/uniprot/Q99P87 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the resistin/FIZZ family.|||Expressed in white but not brown adipose tissue in a variety of organs.|||Homodimer; disulfide-linked.|||Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells. Potentially links obesity to diabetes.|||Secreted http://togogenome.org/gene/10090:Synpo2l ^@ http://purl.uniprot.org/uniprot/Q8BWB1 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Actin-associated protein that may play a role in modulating actin-based shape.|||Belongs to the synaptopodin family.|||cytoskeleton http://togogenome.org/gene/10090:Atf1 ^@ http://purl.uniprot.org/uniprot/P81269|||http://purl.uniprot.org/uniprot/Q9CWS2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. ATF subfamily.|||Binds DNA as a dimer. Interacts with HIPK2 and CDK3. Interacts with MOTS-c, a peptide produced by the mitochondrially encoded 12S rRNA MT-RNR1; the interaction occurs in the nucleus following metabolic stress.|||Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to the Tax-responsive element (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter genes. Represses the expression of FTH1 and other antioxidant detoxification genes. Triggers cell proliferation and transformation (By similarity).|||Nucleus|||Phosphorylated at Ser-196 by HIPK2 in response to genotoxic stress. This phosphorylation promotes transcription repression of FTH1 and other antioxidant detoxification genes. The CDK3-mediated phosphorylation at Ser-63 promotes its transactivation and transcriptional activities (By similarity). Phosphorylated at Ser-63 by RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. http://togogenome.org/gene/10090:Inca1 ^@ http://purl.uniprot.org/uniprot/Q6PKN7 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the INCA family.|||Binds to CDK2-bound cyclins and inhibits the kinase activity of CDK2; binding to cyclins is critical for its function as CDK inhibitor. Inhibits cell growth and proliferation and may play a role in cell cycle control (PubMed:21540187). Required for ING5-mediated regulation of S-phase progression, enhancement of Fas-induced apoptosis and inhibition of cell growth (PubMed:21750715).|||By serum starvation.|||Cytoplasm|||Interacts with CCNA1 (PubMed:21540187). Identified in a complex with CCNA1 and CDK2 (By similarity). Interacts with ZNF16; the interaction inhibits INCA1 activity and induces the cell cycle process (By similarity). Interacts with SPACA9 (By similarity). Interacts with CCNA2, CCNB1 and CCNE1 (By similarity). Interacts with the CCNA1/CDK2 complex (PubMed:21540187). Interacts with ING5, DAZAP2, RNF26, USP15, SPOUT1, DPH7, TRIM26 and RAB5C (By similarity).|||Mice show increased CDK2 activity in spleen with disruption of the splenic architecture.|||Nucleus|||Phosphorylated when part of a complex with CCNA1 and CDK2. http://togogenome.org/gene/10090:Rnf225 ^@ http://purl.uniprot.org/uniprot/Q9D7D1 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Slc25a27 ^@ http://purl.uniprot.org/uniprot/Q9D6D0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Facilitates proton transport across the inner mitochondrial membrane and may dissipate excessive proton gradient associated with oxidative and metabolic stress at neuronal synapses. Regulates glutamate-induced proton conductance in astrocytes, shifting the energy metabolism toward aerobic glycolysis and lactate transfer to neurons for ATP synthesis. Can transport chloride ions with lower efficiency. The transport mechanism remains to be elucidated.|||Homotetramer.|||Mitochondrion inner membrane|||neuron projection http://togogenome.org/gene/10090:Gtpbp2 ^@ http://purl.uniprot.org/uniprot/Q3UJK4 ^@ Induction|||Similarity|||Tissue Specificity ^@ Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. GTPBP1 subfamily.|||Predominantly expressed in thymus, spleen, and testis. Expressed at lower levels in brain, heart, lung, kidney, and skeletal muscle. In testis, specifically expressed in spermatocytes and round spermatids.|||Up-regulated in thioglycolate-elicited mouse peritoneal macrophages. http://togogenome.org/gene/10090:Or5an1b ^@ http://purl.uniprot.org/uniprot/Q7TQR7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Scrn2 ^@ http://purl.uniprot.org/uniprot/Q8VCA8 ^@ Similarity ^@ Belongs to the peptidase C69 family. Secernin subfamily. http://togogenome.org/gene/10090:Abhd10 ^@ http://purl.uniprot.org/uniprot/Q6PE15 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation ^@ Acts as an acyl-protein thioesterase that hydrolyzes fatty acids from acylated residues in proteins (PubMed:31740833). Regulates the mitochondrial S-depalmitoylation of the nucleophilic active site residue of peroxiredoxin-5/PRDX5, a key antioxidant protein, therefore modulating mitochondrial antioxidant ability (PubMed:31740833). Also catalyzes the deglucuronidation of mycophenolic acid acyl-glucuronide, an active metabolite of the immunosuppressant drug mycophenolate (By similarity).|||Belongs to the AB hydrolase superfamily.|||Inhibited by palmostatin-B.|||Mitochondrion http://togogenome.org/gene/10090:Pitpnm3 ^@ http://purl.uniprot.org/uniprot/Q3UHE1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.|||Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro). Binds calcium ions (By similarity).|||Endomembrane system|||Interacts with PTK2B via its C-terminus. http://togogenome.org/gene/10090:Rplp0 ^@ http://purl.uniprot.org/uniprot/P14869|||http://purl.uniprot.org/uniprot/Q5M8R8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL10 family.|||Cytoplasm|||Nucleus|||P0 forms a pentameric complex by interaction with dimers of P1 and P2. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with APEX1. Interacts with FMR1.|||Ribosomal protein P0 is the functional equivalent of E.coli protein L10.|||Ubiquitinated at Lys-264 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling). http://togogenome.org/gene/10090:Acmsd ^@ http://purl.uniprot.org/uniprot/Q8R519 ^@ Function|||Induction|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the metallo-dependent hydrolases superfamily. ACMSD family.|||By streptozocin-induced diabetes. Repressed by low protein diet.|||Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.|||Highest expression in kidney with lower levels in liver and brain.|||Monomer. http://togogenome.org/gene/10090:Smap1 ^@ http://purl.uniprot.org/uniprot/Q91VZ6 ^@ Developmental Stage|||Function|||Sequence Caution|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Contaminating sequence. Potential poly-A sequence.|||Detected in adult brain, lung, heart, liver, ovary and bone marrow. Detected in stromal cells of the red pulp of adult spleen.|||Detected in stromal cells of fetal liver at 10.5 days. Expression was maximal after 14 days of development and decreased thereafter. Detected at low levels after 18 days.|||GTPase activating protein that acts on ARF6. Plays a role in clathrin-dependent endocytosis. May play a role in erythropoiesis.|||Interacts with ARF6. Interacts with clathrin heavy chains via the clathrin box-like motif. http://togogenome.org/gene/10090:Arrdc1 ^@ http://purl.uniprot.org/uniprot/Q99KN1 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the arrestin family.|||Cell membrane|||Functions as an adapter recruiting ubiquitin-protein ligases to their specific substrates (PubMed:23886940, PubMed:27462458). Through an ubiquitination-dependent mechanism plays for instance a role in the incorporation of SLC11A2 into extracellular vesicles (PubMed:27462458). More generally, plays a role in the extracellular transport of proteins between cells through the release in the extracellular space of microvesicles (By similarity). By participating to the ITCH-mediated ubiquitination and subsequent degradation of NOTCH1, negatively regulates the NOTCH signaling pathway (PubMed:23886940).|||Interacts (via PPxY motifs) with ITCH (via WW domains); the interaction is direct and participates in the recruitment of the ubiquitin-protein ligase ITCH to the NOTCH1 receptor. Interacts with ARRB1 and ARRB2; the interaction is direct. Interacts with TSG101; may recruit TSG101 to the plasma membrane. Interacts (via PPxY motifs) with WWP2 (via WW domains); ubiquitinates ARRDC1. Interacts with SLC11A2; controls the incorporation of SLC11A2 into extracellular vesicles through an ubiquitination-dependent mechanism. Interacts with WWP1 (via WW domains). Interacts with NEDD4 (via WW domains). Interacts with PDCD6IP.|||The PPxY motifs mediate interaction with WW domain-containing ubiquitin-protein ligases.|||Ubiquitinated. Ubiquitination by WWP2; promotes localization to extracellular microvesicles. Ubiquitinated by WWP1. http://togogenome.org/gene/10090:Gpr183 ^@ http://purl.uniprot.org/uniprot/Q3U6B2 ^@ Disruption Phenotype|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in mature B-cells and increases in expression early after activation, before being down-regulated in germinal center B-cells (PubMed:19597478). Expressed in astrocytes (PubMed:25297897). Specifically expressed in CD4(+) dendritic cells but not in CD8(+) dendritic cells (PubMed:23682316, PubMed:23502855). Expressed in monocyte/osteoclasts precursors and mature osteoclasts (PubMed:26438360).|||G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes (PubMed:19597478, PubMed:19615922, PubMed:21844396, PubMed:21796211, PubMed:21796212, PubMed:27147029). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (PubMed:21796211, PubMed:21796212). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (PubMed:21796211, PubMed:21796212, PubMed:27147029). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (PubMed:21796211, PubMed:21796212). Collaborates with CXCR5 to mediate B-cell migration; probably by forming a heterodimer with CXCR5 that affects the interaction between of CXCL13 and CXCR5 (PubMed:21948984, PubMed:22913878). Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions (PubMed:19615922, PubMed:19597478, PubMed:21844396). Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses (PubMed:19615922). Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand (PubMed:27147029). Promotes follicular helper T (Tfh) cells differentiation by positioning activated T-cells at the follicle-T-zone interface, promoting contact of newly activated CD4 T-cells with activated dendritic cells and exposing them to Tfh-cell-promoting inducible costimulator (ICOS) ligand (PubMed:27147029). Expression in splenic dendritic cells is required for their homeostasis, localization and ability to induce B- and T-cell responses: GPR183 acts as a chemotactic receptor in dendritic cells that mediates the accumulation of CD4(+) dendritic cells in bridging channels (PubMed:23682316, PubMed:23502855). Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages (PubMed:25297897, PubMed:27166278). Promotes osteoclast precursor migration to bone surfaces (PubMed:26438360). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha (By similarity). Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).|||GSK682753A (8-[(2E)-3-(4-chlorophenyl)prop-2-enoyl]-3-[(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one), an inverse agonist, selectively inhibits the constitutive activity of GPR183 with high potency and efficacy.|||Homodimer and heterodimer. Heterodimerizes with CXCR5; leading to modulate the interaction between of CXCL13 and CXCR5.|||Mice display a reduction in the early antibody response to a T-dependent antigen (PubMed:19597478). B-cells fail to move to the outer follicle at day 2 of activation, and instead are found in the follicle center (PubMed:19615922). Mice have normal numbers of B- and T-cells and organized follicles and T-cell compartments are present (PubMed:19615922). Mice show a decreased number of splenic CD4(+) dendritic cells and defective priming of T- and B-cell response (PubMed:23682316, PubMed:23502855). Reduced follicular helper T (Tfh) cells (PubMed:27147029). T-cells fail to accumulate in the outer T zone at either time point and instead remain dispersed throughout the T zone (PubMed:27147029).|||Up-regulated during B-cell maturation in the bone marrow, and is expressed in mature recirculating B-cells in bone marrow, spleen and lymph nodes (PubMed:19597478). Up-regulated in B-cells after BCR and CD40 engagement (PubMed:19597478). Down-regulated by lipopolysaccharide (LPS) in astrocytes (PubMed:27166278). Expression is directly down-regulated by BCL6 (PubMed:25176650). http://togogenome.org/gene/10090:Tmcc1 ^@ http://purl.uniprot.org/uniprot/A0A0N4SWB9|||http://purl.uniprot.org/uniprot/Q69ZZ6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TEX28 family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum membrane protein that promotes endoplasmic reticulum-associated endosome fission. Localizes to contact sites between the endoplasmic reticulum and endosomes and acts by promoting recruitment of the endoplasmic reticulum to endosome tubules for fission. Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane.|||May form homodimers and heterodimers with TMCC2 or TMCC3 via the coiled-coil domains. Interacts with ribosomal proteins RPL4 and RPS6. http://togogenome.org/gene/10090:Or8k37 ^@ http://purl.uniprot.org/uniprot/A0A1L1STZ9 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Wipf1 ^@ http://purl.uniprot.org/uniprot/Q8K1I7 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the verprolin family.|||Binds to WAS within the N-terminal region, at a site distinct from the CDC42-binding site. Binds profilin and actin (By similarity). Binds to WASL. Interacts with DBNL. Interacts with DBNL. Interacts with FNBP1L (via the SH3 domain) (By similarity).|||Cytoplasmic vesicle|||Plays a role in the reorganization of the actin cytoskeleton. Contributes with NCK1 and GRB2 in the recruitment and activation of WASL. May participate in regulating the subcellular localization of WASL, resulting in the disassembly of stress fibers in favor of filopodia formation (By similarity). Plays a role in the formation of cell ruffles.|||Recruited to PIP5K-induced vesicle surfaces in the absence of functional WASL.|||cytoskeleton|||ruffle http://togogenome.org/gene/10090:Acpp ^@ http://purl.uniprot.org/uniprot/Q8CE08 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma (By similarity).|||Belongs to the histidine acid phosphatase family.|||Cell membrane|||Expressed in salivary gland, thymus and thyroid gland.|||Homodimer; dimer formation is required for phosphatase activity.|||In addition to its tyrosine phosphatase activity, also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP. This extracellular adenosine leads to a decrease in chronic pain by activating A1R in nociceptive neurons.|||Lysosome membrane|||Null mice display greater thermal hyperalgesia (pain sensitivity) and mechanical allodynia. No thiamine monophosphatase (TMPase) activity detected in dorsal root ganglion (DRG) neurons.|||Secreted|||Widely expressed in prostate lobes, brain, kidney, liver, lung, muscle, placenta, salivary gland, spleen, thyroid and thymus. Locates to Schwann cells and fibroblasts. Expressed in peptidergic and non-peptidergic nociceptive (pain-sensing) neurons. Preferentially expressed in non-peptidergic doral root ganglia neurons. http://togogenome.org/gene/10090:Synj2 ^@ http://purl.uniprot.org/uniprot/D3YZB2|||http://purl.uniprot.org/uniprot/E9Q4P5|||http://purl.uniprot.org/uniprot/F8WHD8|||http://purl.uniprot.org/uniprot/Q3TTB3|||http://purl.uniprot.org/uniprot/Q9D2G5 ^@ Domain|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the synaptojanin family.|||Binds GRB2 and OMP25.|||Cell membrane|||Cytoplasm|||In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.|||Inositol 5-phosphatase which may be involved in distinct membrane trafficking and signal transduction pathways. May mediate the inhibitory effect of Rac1 on endocytosis (By similarity).|||Membrane raft|||Presynapse|||Sequencing errors.|||The C-terminal proline-rich region mediates binding to the SH3 domain-containing protein GRB2.|||Ubiquitously expressed, with the highest levels in heart and brain. Detected in cortex, cerebellum and olfactory bulb. Expressed in the testis.|||cytoskeleton http://togogenome.org/gene/10090:Miga2 ^@ http://purl.uniprot.org/uniprot/Q8BK03 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitoguardin family.|||Homodimer and heterodimer; forms heterodimers with MIGA1. Interacts with PLD6/MitoPLD. Interacts (via phosphorylated FFAT motif) with MOSPD2 (By similarity).|||Mitochondrial fragmentation: mitochondria become round and show loss of cristae (PubMed:26711011). Female mice show decreased quality of oocytes (PubMed:26716412). Mice lacking both Miga1 and Miga2 show strongly reduced quality of oocytes and are subfertile (PubMed:26716412).|||Mitochondrion outer membrane|||Phosphorylation at Ser-295 of the FFAT motif activates interaction with MOSPD2.|||Regulator of mitochondrial fusion (PubMed:26711011). Acts by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating the formation of PLD6/MitoPLD dimers. May act by regulating phospholipid metabolism via PLD6/MitoPLD (By similarity).|||The FFAT motif is involved in the interaction with MOSPD2 and its phosphorylation regulates this interaction. http://togogenome.org/gene/10090:Tbx3 ^@ http://purl.uniprot.org/uniprot/P70324|||http://purl.uniprot.org/uniprot/Q3ULL3|||http://purl.uniprot.org/uniprot/Q4VA43 ^@ Caution|||Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, expressed in the otic vesicle, also known as the otocyst (at protein level) (PubMed:33795231). Between 10.5-12.0 dpc, expressed in various regions of the developing ear, including the developing vestibular system and the epithelium of the cochlear duct (at protein level) (PubMed:33795231). Expressed in the blastocyst at 3.5 dpc (PubMed:8853987). At 7.5 dpc, expressed in the extraembryonic endoderm and in the mesoderm of the chorion and amnion (PubMed:8853987). At 9.5 dpc, in the facial region, forelimb, pharyngeal epithelium, mesenchyme of the pharyngeal arches and the lateral body wall and, at 12.5 dpc, in the trigeminal ganglia, developing central nervous system and in the mammary buds (PubMed:8853987). Expressed in a continuous stripe of mesenchyme in the ventro-lateral body wall between the fore and hind limb buds at day 10.5-11.5 dpc (PubMed:16222716). Also expressed in the epithelium of the first and third mammary placodes at 10.5 dpc, and in all five pairs of mammary placodes between 11.5 and 13.5 dpc (PubMed:16222716).|||Conditional knockdown targeted mainly to lung mesenchyme causes lung hypoplasia at 18.5 dpc (PubMed:27720610). Conditional knockdown targeted mainly to the otic epithelium disrupts inner ear morphogenesis, which is exacerbated by simultaneous conditional knockdown of TBX2 (PubMed:33795231). Simultaneous conditional knockdown of TBX2 and TBX3 targeted mainly to lung mesenchyme causes severe bleeding from 10.5 dpc and embryos die shortly thereafter, perhaps as a result of knockdown in the developing heart (PubMed:27720610).|||In adults, highest levels in lung. Also found in brain, heart, kidney, liver and ovary.|||Interacts with PML.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Nucleus|||Transcriptional repressor involved in developmental processes (By similarity). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (By similarity). Probably plays a role in limb pattern formation (By similarity). Required for mammary placode induction, and maintenance of the mammary buds during development (PubMed:16222716). Involved in branching morphogenesis in both developing lungs and adult mammary glands, via negative modulation of target genes; acting redundantly with TBX2 (PubMed:27720610, PubMed:16222716). Required, together with TBX2, to maintain cell proliferation in the embryonic lung mesenchyme; perhaps acting downstream of SHH, BMP and TGFbeta signaling (PubMed:27720610). Involved in modulating early inner ear development, acting independently of, and also redundantly with, TBX2 in different subregions of the developing ear (PubMed:33795231). Acts as a negative regulator of PML function in cellular senescence (By similarity). http://togogenome.org/gene/10090:Cyb561a3 ^@ http://purl.uniprot.org/uniprot/Q6P1H1 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 17.5 dpc, it is primarily expressed in lung, spleen, thymus, testis, placenta, small intestine and stomach.|||Binds 2 heme b groups non-covalently.|||Homodimer.|||Late endosome membrane|||Lysosome membrane|||N-glycosylated.|||Present in lung, spleen, thymus and testis. Present at low level in brain, heart, liver and kidney. Expressed in the alveolar macrophages of the lung, in the white pulp of the spleen, widespread in the thymus, and in the Sertoli cells of the testis (at protein level).|||Transmembrane reductase that uses ascorbate as an electron donor in the cytoplasm and transfers electrons across membranes to reduce iron cations Fe(3+) into Fe(2+) in the lumen of the late endosome and lysosome (PubMed:16911521). Reduced iron can then be extruded from the late endosome and lysosome to the cytoplasm by divalent metal-specific transporters (Probable). It is therefore most probably involved in endosomal and lysosomal cellular iron homeostasis (Probable). http://togogenome.org/gene/10090:Gm20830 ^@ http://purl.uniprot.org/uniprot/J3KML6 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Or4c115 ^@ http://purl.uniprot.org/uniprot/F7BL62 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Aoc3 ^@ http://purl.uniprot.org/uniprot/O70423 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the copper/topaquinone oxidase family.|||Binds 1 copper ion per subunit.|||Binds 2 calcium ions per subunit.|||Cell adhesion protein that participates in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has a monoamine oxidase activity. May play a role in adipogenesis (By similarity).|||Contains 1 topaquinone per subunit.|||Homodimer; disulfide-linked (By similarity). Forms a heterodimer with AOC2 (By similarity).|||Membrane|||N- and O-glycosylated.|||Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue. http://togogenome.org/gene/10090:Hps4 ^@ http://purl.uniprot.org/uniprot/Q99KG7 ^@ Disease Annotation|||Function|||Subunit|||Tissue Specificity ^@ Component of the BLOC-3 complex, a complex that acts as a guanine exchange factor (GEF) for RAB32 and RAB38, promotes the exchange of GDP to GTP, converting them from an inactive GDP-bound form into an active GTP-bound form. The BLOC-3 complex plays an important role in the control of melanin production and melanosome biogenesis and promotes the membrane localization of RAB32 and RAB38.|||Component of the biogenesis of lysosome-related organelles complex-3 (or BLOC-3), a heterodimer of HPS1 and HPS4. HPS4 and the BLOC-3 complex interact with the GTP-bound form of RAB9B but not with the GDP-bound form of RAB9B (By similarity). HPS4 and the BLOC-3 complex interact with the GTP-bound form of RAB9A but not with the GDP-bound form of RAB9A (PubMed:20048159, PubMed:26620560). HPS4 does not interact RAB4A and RAB7A (PubMed:26620560).|||Defects in Hps4 are the cause of the light ear (le) mutant which exhibits hypopigmentation associated with defects of multiple cytoplasmic organelles, including melanosomes, lysosomes, and granular elements of platelets (PubMed:11836498).|||Highly expressed in heart, brain, liver and testis. Expressed at lower level in skeletal muscle. http://togogenome.org/gene/10090:Mtmr3 ^@ http://purl.uniprot.org/uniprot/B1ATD5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.|||Cytoplasm|||Membrane http://togogenome.org/gene/10090:AI467606 ^@ http://purl.uniprot.org/uniprot/Q8C708 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Pcdhgb7 ^@ http://purl.uniprot.org/uniprot/Q91XX3 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Odc1 ^@ http://purl.uniprot.org/uniprot/P00860 ^@ Activity Regulation|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the Orn/Lys/Arg decarboxylase class-II family.|||Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis.|||Expressed during testis development in the outer part of the seminiferous tubules.|||Homodimer. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers (PubMed:8106349, PubMed:10378276). Does not form a heterodimer with AZIN2 (PubMed:24967154).|||Inhibited by antizymes (AZs) OAZ1, OAZ2 and OAZ3 in response to polyamine levels. AZs inhibit the assembly of the functional homodimer by binding to ODC monomers. Additionally, OAZ1 targets ODC monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome. http://togogenome.org/gene/10090:Dppa5a ^@ http://purl.uniprot.org/uniprot/Q9CQS7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the KHDC1 family.|||Cytoplasm|||Down-regulated by retinoic acid in embryonic carcinoma (EC) cells and in developing germ cells.|||Involved in the maintenance of embryonic stem (ES) cell pluripotency. Dispensable for self-renewal of pluripotent ES cells and establishment of germ cells. Associates with specific target mRNAs.|||Mice develop normally and are fertile. ES cells derived from these mice demonstrate normal morphology, proliferation and differentiation.|||Pluripotent cell-specific. Expressed in zygotes, cleavage-stage embryos and blastocysts, embryonic stem (ES) and embryonic germ (EG) cells. Detected in both the trophectoderm (TE) and inner cell mass (ICM) of blastocysts. More abundant in the ICM than TE at 3.5 dpc blastocyst stage. Expressed in primordial germ (PGC) cells from 10.5 to 13.5 dpc. Expressed in developing gonads from 11.5 to 15.5 dpc. Progressively undetectable in ovary from 13.5 to 15.5 dpc. Undetectable in testis after 15.5 dpc. Not expressed in somatic cells at 13.5 dpc (at protein level). Expressed in embryonic stem (ES) and embryonic carcinoma (EC) cells. Not detected during the differentiation of stem cells or midgestation embryos nor in neonatal tissues. Weakly expressed or not detected in oocytes and fertilized eggs. http://togogenome.org/gene/10090:Gstt1 ^@ http://purl.uniprot.org/uniprot/Q64471|||http://purl.uniprot.org/uniprot/Q9DCY6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Theta family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Also binds steroids, bilirubin, carcinogens and numerous organic anions. Has dichloromethane dehalogenase activity.|||Cytoplasm|||Homodimer.|||In liver, highest expression found in central vein limiting plate hepatocytes. Also expressed in interlobular bile duct epithelial cells. In lung, expressed in club cells and ciliated cells of the bronchiolar epithelium and in type II alveolar cells of the lung parenchyma.|||Nucleus http://togogenome.org/gene/10090:Odf2l ^@ http://purl.uniprot.org/uniprot/Q9D478 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Acts as a suppressor of ciliogenesis, specifically, the initiation of ciliogenesis.|||Belongs to the ODF2 family.|||centriolar satellite|||centriole|||centrosome|||cilium basal body http://togogenome.org/gene/10090:Plp1 ^@ http://purl.uniprot.org/uniprot/P60202|||http://purl.uniprot.org/uniprot/Q3UYM8 ^@ Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the myelin proteolipid protein family.|||Cell membrane|||Defects in Plp1 are the cause of the dysmyelinating diseases Jimpy and Rumpshaker (rsh).|||Membrane|||Myelin membrane|||This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin. http://togogenome.org/gene/10090:Sycp1 ^@ http://purl.uniprot.org/uniprot/Q62209 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Detected in testis (PubMed:15937223). Detected in spermatocytes (at protein level) (PubMed:22761579).|||Major component of the transverse filaments of synaptonemal complexes, formed between homologous chromosomes during meiotic prophase (PubMed:16717126). Required for normal assembly of the central element of the synaptonemal complexes (PubMed:15937223). Required for normal centromere pairing during meiosis (PubMed:22761579). Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility (PubMed:15937223).|||Mice appear generally healthy, but display complete sterility, due to defective meiosis during germ cell development. Ovaries and testes from mutant mice have strongly reduced weight relative to wild-type. Ovaries display an absence of growing follicles and oocytes. Testes show a complete lack of spermatids and spermatozoa. Synaptonemal complexes from mutant spermatocytes form normal axial elements, but lack the central element; chromosomes do not synapse properly, cross-overs are rare, and DNA repair after meiotic double-strand breaks is impaired.|||Nucleus|||Structural component of synaptonemal complexes (PubMed:15937223, PubMed:16717126, PubMed:22761579). Homotetramer that consists of an N-terminal four-helical bundle that bifurcates into two elongated C-terminal dimeric coiled coils. This tetrameric building block potentially self-assembles into a supramolecular zipper-like lattice to mediate meiotic chromosome synapsis. Self-assembly is likely initiated by local proton density at chromosome axis, which is predicted to trigger antiparallel back to back assembly of adjacent C-terminal ends into tetrameric structures that anchor to chromosomal DNA. Then the N-terminal ends are predicted to undergo cooperative antiparallel head to head assembly at the midline of synaptonemal complexes central element to form a zipper-like lattice between properly aligned homologous chromosomes (By similarity). The nascent synapsis generated by SYCP1 is stabilized through interaction with central element proteins SYCE1 and SYCE2 (PubMed:15944401, PubMed:16968740). Forms a complex with EWSR1, PRDM9, SYCP3 and REC8; complex formation is dependent of phosphorylated form of REC8 and requires PRDM9 bound to hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 (PubMed:27932493). Interacts with SPO16 (PubMed:30949703).|||The molecule is in a coiled coil structure that is formed by 4 polypeptide chains. The N-terminal region exhibits a prominent seven-residues periodicity.|||centromere http://togogenome.org/gene/10090:Pllp ^@ http://purl.uniprot.org/uniprot/Q9DCU2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Appears to be involved in myelination. Could also participate in ion transport events as addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K(+)-selective (By similarity).|||Belongs to the MAL family.|||Hexamer arranged as a trimer of two plasmolipin subunits.|||Membrane http://togogenome.org/gene/10090:Enkd1 ^@ http://purl.uniprot.org/uniprot/Q7TSV9 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with alpha-tubulin (By similarity). Interacts (via central region) with CCP110 (via N-terminal region); competes with CEP97 for binding to CCP110 (PubMed:35301795).|||Microtubule-binding protein which regulates microtubule organization and stability (By similarity). Promotes the stability of astral microtubules and facilitates the proper orientation of the mitotic spindle (By similarity). This allows the oriented division of basal keratinocytes and contributes to epidermal stratification (PubMed:35197565). Required for the assembly of both primary and motile cilia (PubMed:35301795, PubMed:35072334). Destabilizes the interaction between CCP110 and CEP97 by competing with CEP97 for binding to CCP110 which promotes the removal of CCP110 and CEP97 from the mother centriole and allows the initiation of ciliogenesis (PubMed:35301795).|||Severely impaired epidermal barrier function with a significant reduction in the thickness of the granular and spinous layers of the epidermis (PubMed:35197565). Misoriented division of basal keratinocytes and significantly reduced proliferation rate of basal keratinocytes and suprabasal cells (PubMed:35197565). Ciliogenesis defects in multiple organs (PubMed:35301795). Retinal photoreceptor cilia numbers are greatly decreased, leading to defective vision, and there is also a decreased number of renal primary cilia as well as a reduced percentage of ciliated cells in the tracheal epithelium (PubMed:35301795). Impaired cardiac function (PubMed:35301795). Males are fertile but a significant proportion of spermatozoa are aberrant with no tails (PubMed:35301795).|||Widely expressed with highest levels in testis and lung.|||centriole|||centrosome|||cilium|||cilium axoneme|||cilium basal body|||spindle|||spindle pole http://togogenome.org/gene/10090:Vmo1 ^@ http://purl.uniprot.org/uniprot/Q5SXG7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the VMO1 family.|||Secreted http://togogenome.org/gene/10090:Zfp35 ^@ http://purl.uniprot.org/uniprot/P15620 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May act to control gene activity during the pachytene stage of meiotic prophase. May function as a transcription activator.|||Nucleus|||Selectively expressed in adult testis. http://togogenome.org/gene/10090:Shtn1 ^@ http://purl.uniprot.org/uniprot/Q8K2Q9 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the shootin family.|||Expressed in hippocampal neurons (PubMed:17030985).|||Expressed in the developing brain. Expressed in the developing cortical plate at 11 and 14 dpc. Expressed in multipolar cells at 14 dpc (at protein level). Expressed in the developing cortical plate of the telencephalon (PubMed:23864681).|||Interacts with L1CAM; this interaction occurs at axonal growth cones. Interacts with actin filament retrograde flow; this interaction is enhanced in a netrin-1- and PAK1-dependent manner and promotes F-actin-substrate coupling and concomitant formation of traction forces at axonal growth cones. Interacts with RUFY3 (By similarity). Interacts with PFN2 (PubMed:19403918). Interacts (via N-terminus) with KIF20B; this interaction is direct and promotes the association of SHTN1 to microtubules in primary neurons (PubMed:23864681). Associates with microtubule (PubMed:23864681).|||Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth (PubMed:23864681). Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth (By similarity). In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex (PubMed:23864681). Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons (PubMed:23864681).|||Perikaryon|||Phosphorylated on Ser-101 and Ser-249 by PAK1 through a CDC42- and RAC1-dependent signaling pathway, which enhances its association with F-actin retrograde flow in filopodia and lamellipodia of axonal growth cones. Phosphorylation on Ser-101 and Ser-249 is increased by netrin-1.|||The N-terminus region is necessary for interaction with actin retrograde filament flow and accumulation in neuronal growth cones.|||axon|||cytoskeleton|||filopodium|||growth cone|||lamellipodium http://togogenome.org/gene/10090:Iqca1l ^@ http://purl.uniprot.org/uniprot/A6H690 ^@ Similarity ^@ Belongs to the AAA ATPase family. http://togogenome.org/gene/10090:Or4f7 ^@ http://purl.uniprot.org/uniprot/A2AVW1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fbxw5 ^@ http://purl.uniprot.org/uniprot/Q9QXW2 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FBXW5 family.|||Cytoplasm|||Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXW5) composed of CUL1, SKP1, RBX1 and FBXW5. Component of the DCX(FBXW5) E3 ubiquitin ligase complex, at least composed of (CUL4A or CUL4B), DDB1, FBXW5 and RBX1. Interacts with CDC20, TSC1, TSC2 and SASS6 (By similarity). Interacts with EPS8. Interacts with TNFAIP8L1; TNFAIP8L1 competes with TSC2 to bind FBXW5 increasing TSC2 stability by preventing its ubiquitination.|||Phosphorylated at Ser-151 by PLK4 during the G1/S transition, leading to inhibit its ability to ubiquitinate SASS6.|||Substrate recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. Substrate-specific adapter of the DCX(FBXW5) E3 ubiquitin-protein ligase complex which mediates the polyubiquitination and subsequent degradation of TSC2. May also act as a negative regulator of MAP3K7/TAK1 signaling in the interleukin-1B (IL1B) signaling pathway. Substrate recognition component of the SCF(FBXW5) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of SASS6 during S phase, leading to prevent centriole reduplication (By similarity). The SCF(FBXW5) complex also mediates ubiquitination and degradation of actin-regulator EPS8 during G2 phase, leading to the transient degradation of EPS8 and subsequent cell shape changes required to allow mitotic progression.|||The D-box (destruction box) mediate the interaction with APC proteins, and acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.|||The F-box domain mediates interaction with components of SCF (SKP1-CUL1-F-box protein) complexes, while WD repeats mediate interaction with components of DCX (DDB1-CUL4-X-box) complexes.|||Ubiquitinated and degraded by the APC/C complex during mitosis and G1 phase.|||Widely expressed in adult and embryonal tissues. http://togogenome.org/gene/10090:Or2b2b ^@ http://purl.uniprot.org/uniprot/A2BDD3|||http://purl.uniprot.org/uniprot/K9J6X0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adprm ^@ http://purl.uniprot.org/uniprot/Q99KS6 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ADPRibase-Mn family.|||Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose. May be involved in immune cell signaling as suggested by the second-messenger role of ADP-ribose, which activates TRPM2 as a mediator of oxidative/nitrosative stress (By similarity).|||Monomer. http://togogenome.org/gene/10090:Rps19 ^@ http://purl.uniprot.org/uniprot/Q9CZX8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic ribosomal protein eS19 family.|||Component of the small ribosomal subunit (PubMed:36517592). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity). Interacts with RPS19BP1 (PubMed:16289379).|||Component of the small ribosomal subunit (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:36517592). Required for pre-rRNA processing and maturation of 40S ribosomal subunits (By similarity). Required for pre-rRNA processing and maturation of 40S ribosomal subunits. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).|||Cytoplasm|||nucleolus http://togogenome.org/gene/10090:Ocrl ^@ http://purl.uniprot.org/uniprot/Q6NVF0 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.|||Catalyzes the hydrolysis of the 5-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic activity towards PtdIns(4,5)P2. Able also to hydrolyze the 5-phosphate of inositol 1,4,5-trisphosphate and of inositol 1,3,4,5-tetrakisphosphate. Regulates traffic in the endosomal pathway by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with endosomes. Involved in primary cilia assembly. Acts as a regulator of phagocytosis, hydrolyzing PtdIns(4,5)P2 to promote phagosome closure, through attenuation of PI3K signaling.|||Cytoplasmic vesicle|||Early endosome membrane|||Endosome|||Interacts with APPL1, PHETA1/SES1 and PHETA2/SES2; APPL1-binding and PHETA1-binding are mutually exclusive (By similarity). Interacts with clathrin heavy chain. Interacts with several Rab GTPases, at least RAB1B, RAB5A, RAB6A, RAB8A and RAB31; these interactions may play a dual role in targeting OCRL to the specific membranes and stimulating the phosphatase activitye (PubMed:25869668). Interaction with RAB8A modulates OCRL recruitment to cilia. Interacts with RAB31 (By similarity). Interacts with INPP5F (PubMed:25869668).|||The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature (By similarity).|||cilium|||clathrin-coated pit|||phagosome membrane|||photoreceptor outer segment|||trans-Golgi network http://togogenome.org/gene/10090:Prl2b1 ^@ http://purl.uniprot.org/uniprot/B9EHM9|||http://purl.uniprot.org/uniprot/Q9DAZ2 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the somatotropin/prolactin family.|||Expressed specifically in placenta. Expressed at high levels in trophoblast cells from both junctional and labyrinth zones of the chorioallantoic placenta the last week of gestation.|||Secreted http://togogenome.org/gene/10090:Tmed2 ^@ http://purl.uniprot.org/uniprot/A2RS53|||http://purl.uniprot.org/uniprot/Q9R0Q3 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the EMP24/GP25L family.|||COPI-coated vesicle membrane|||Cytoplasmic vesicle membrane|||Embryonic lethal for homozygotes with Glu-15 in the signal peptide. Animals do not show Tmed2 protein expression and also have reduced protein levels of Tmed7 and Tmed10. Prior to death at mid-gestation, embryos exhibit developmental delay, abnormal rostral-caudal elongation, randomized heart looping, and absence of the labyrinth layer of the placenta.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Expressed during embryonal and placental development.|||Golgi stack membrane|||Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway but also in post-Golgi membranes. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED10 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by PGAP1 and MPPE1. In COPI vesicle-mediated retrograde transport inhibits the GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing immature uncoating and allowing cargo selection to take place. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Facilitates CASR maturation and stabilization in the early secretory pathway and increases CASR plasma membrane targeting. Proposed to be involved in organization of intracellular membranes such as the maintenance of the Golgi apparatus. May also play a role in the biosynthesis of secreted cargo such as eventual processing (By similarity). Required for morphogenesis of embryo and placenta.|||Membrane|||Monomer and homodimer in the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and Golgi. Probably oligomerizes with other members of the EMP24/GP25L family such as TMED7, TMED9 and TMED10. Interacts (via GOLD domain) with TMED10 (via GOLD domain). Associates with the COPI vesicle coat (coatomer); TMED10:TMED2 heterotetramers are proposed to be involved in coatomer association. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED2. Interacts with SEC23A; indicative for an association of TMED2 with the COPII vesicle coat. Interacts with ARF1 and ARFGAP1. Interacts with CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATL1. Interacts with KDELR1; the interaction is decreased by KDEL ligand. Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with CASR (immaturely glycosylated form); the interaction occurs in the endoplasmic reticulum-Golgi intermediate compartment or cis-Golgi. Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with GORASP1 and GORASP2. Found in a complex composed at least of SURF4, TMED2 and TMED10 (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Get3 ^@ http://purl.uniprot.org/uniprot/O54984 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1/WRB and CAMLG/GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-CAMLG receptor, and returning it to the cytosol to initiate a new round of targeting.|||Belongs to the arsA ATPase family.|||Causes early embryonic lethality.|||Cytoplasm|||Endoplasmic reticulum|||Homodimer. Component of the Golgi to ER traffic (GET) complex, which is composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40. Within the complex, CAMLG and GET1 form a heterotetramer which is stabilized by phosphatidylinositol binding and which binds to the GET3 homodimer. Interacts with CAMLG/GET2 (via N-terminus). GET3 shows a higher affinity for CAMLG than for GET1. Interacts with SERP1 and SEC61B.|||nucleolus http://togogenome.org/gene/10090:Agtr1b ^@ http://purl.uniprot.org/uniprot/P29755|||http://purl.uniprot.org/uniprot/Q32MF7|||http://purl.uniprot.org/uniprot/Q8BU69 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the G-protein coupled receptor 1 family.|||C-terminal Ser or Thr residues may be phosphorylated.|||Cell membrane|||Interacts with MAS1 (By similarity). Interacts with ARRB1 (By similarity). Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA (By similarity).|||Membrane|||Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney. The activated receptor in turn couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C.|||Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney. The activated receptor in turn couples to G-alpha proteins G(q) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. http://togogenome.org/gene/10090:Akap13 ^@ http://purl.uniprot.org/uniprot/E9Q394 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Complete embryonic lethality (PubMed:16469733, PubMed:20139090). Mutant embryos are present at the expected Mendelian rate and develop normally up to 8 dpc. At 10 dpc, mutant embryos appear smaller, have an enlarged heart and pericardiac effusion. The myocardium is thinner than normal and has reduced trabeculation. Sarcomeres are abnormal with incompleteley formed myofilaments that end blindly and do not form Z-disks, indicating a defect in cardiomyocyte differentiation (PubMed:20139090). Heterozygous mice are born at the expected Mendelian frequency and appear grossly normal (PubMed:16469733, PubMed:20139090). Heterozygous mice display a blunted response to glucocorticoids (PubMed:16469733). Heterozygous mice display reduced bone volume relative to body size, but no change of bone length. Heterozygous mice display reduced bone mineral density and reduced trabecular bone, similar to osteoporotic bone. The number of osteoblasts in trabecular bone is reduced (PubMed:25892096).|||Cytoplasm|||Detected in embryonic heart, limb bud, first branchial arch and forebrain (at protein level) (PubMed:20139090). Detected in heart (PubMed:20139090). Detected in perichondrium, but not in the bone growth plate (PubMed:25892096).|||Detected in head folds, notochord and somites at 8.5 dpc, with little or no expression in the looping heart. Detected in heart, vasculature, eye, ear, somites, gut and brain at 9.5 dpc. Expression in the heart increases by 10.5 dpc. Highly expressed in atrial and ventricular myocardium and endocardium, trabeculae and outflow tract at 14.5 dpc. Additionally, detected in skeletal muscle, tongue, gut, kidney, lung, urinary system and in the choroid plexus of the brain.|||Interacts with the cAMP-dependent protein kinase (PKA) holoenzyme and with the regulatory subunit PRKAR2A (PubMed:21102438, PubMed:24161911, PubMed:23658642). Interacts with RHOA. Interacts also with RHOB and RHOC. Identified in a ternary complex with RHOA and PRKAR2A. Identified in a complex with NR3C1 and RHOA (By similarity). Interacts with BRAF and KSR1. Identified in a complex with BRAF and KSR1 (PubMed:21102438). Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK. Interacts (phosphorylated form) with YWHAB and YWHAZ. Interaction with YWHAB inhibits activation of RHOA, interferes with PKN1 binding and activation of MAP kinases. Interacts with GNA12 (By similarity). Interacts with IKBKB (PubMed:23090968). Interacts with ESR1, THRA, PPARA and NME2 (By similarity). Interacts (via the C-terminal domain after the PH domain) with MEF2C and RXRB (PubMed:20139090). Interacts (via the C-terminal domain after the PH domain) with PRKD1 (PubMed:23658642, PubMed:24161911).|||Membrane|||Nucleus|||Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor. May also activate other Rho family members (PubMed:23658642). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14. Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity. Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (By similarity). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2. Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (By similarity). Functions as scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (PubMed:24161911). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (By similarity). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (PubMed:20139090). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:23658642, PubMed:24161911). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:17537920, PubMed:24161911). Plays a role in osteogenesis (PubMed:25892096).|||The C-terminal domain after the PH domain is involved in protein-protein interactions that are required for normal, compensatory cardiac hypertrophy in response to pressure overload.|||The DH domain is sufficient for interaction with RHOA, and for guanine nucleotide exchange (GEF) activity with RHOA. Forms that lack C-terminal regulatory domains have transforming activity and function as oncogenes.|||The PH domain does not play a role in lipid-binding. Instead, it inhibits the guanine nucleotide exchange (GEF) activity of the isolated DH domain (in vitro).|||Up-regulated in the left heart ventricle in response to phenylephrine.|||cell cortex|||cytoskeleton|||cytosol http://togogenome.org/gene/10090:Tmem262 ^@ http://purl.uniprot.org/uniprot/D3Z338 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.|||Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, SLCO6C1, TMEM249, TMEM262 and EFCAB9 (PubMed:34225353). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (PubMed:34225353). The auxiliary CATSPERB, CATSPERG2, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (PubMed:34225353). SLCO6C1 interacts with CATSPERE and TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex (PubMed:34225353). C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (Probable).|||flagellum membrane http://togogenome.org/gene/10090:2310022B05Rik ^@ http://purl.uniprot.org/uniprot/Q8C3W1 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Higd1b ^@ http://purl.uniprot.org/uniprot/Q99JY6 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Rfx1 ^@ http://purl.uniprot.org/uniprot/P48377 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RFX family.|||Homodimer; binds DNA as a homodimer (By similarity). Heterodimer; heterodimerizes with RFX2 and RFX3 (PubMed:15229132).|||Nucleus|||Regulatory factor essential for MHC class II genes expression. Binds to the X boxes of MHC class II genes (By similarity). http://togogenome.org/gene/10090:Zfp318 ^@ http://purl.uniprot.org/uniprot/Q99PP2 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a transcriptional coactivator for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and in particular, during meiotic division.|||Acts as a transcriptional corepressor for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and in particular, during meiotic division.|||Homodimer. Heterodimer of isoform 1 and isoform 2. Isoform 1 and isoform 2 interact with AR.|||Isoform 1 and isoform 2 are highly expressed in testis, moderately expressed in adrenal gland and uterus and faintly expressed in brain, kidney and liver. Isoform 1 is expressed more in adrenal gland, uterus and liver than isoform 2 is. Expression during testicular development of isoform 1 and isoform 2 is restricted to spermatocytes at the pachytene stage of meiotic prophase and to round and elongated spermatids.|||Nucleus http://togogenome.org/gene/10090:Fancb ^@ http://purl.uniprot.org/uniprot/Q5XJY6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM.|||DNA repair protein required for FANCD2 ubiquitination.|||Nucleus http://togogenome.org/gene/10090:Fanca ^@ http://purl.uniprot.org/uniprot/Q9JL70 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM (By similarity). In complex with FANCF, FANCG and FANCL, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins (By similarity). The complex with FANCC and FANCG may also include EIF2AK2 and HSP70. Interacts with FAAP20; interaction is direct (By similarity).|||Cytoplasm|||DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be involved in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability (By similarity).|||Mainly expressed in testis and lymphoid tissues like thymus, lymph nodes, and spleen, and at lower levels in kidney and ovary.|||Nucleus|||Phosphorylated primarily on serine residues. Phosphorylation is required for the formation of the nuclear complex (By similarity). http://togogenome.org/gene/10090:Nt5c1b ^@ http://purl.uniprot.org/uniprot/Q91YE9 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by ADP.|||Belongs to the 5'-nucleotidase type 3 family.|||Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, AMP is the major substrate.|||Cytoplasm|||Expressed at highest levels in testis. Also expressed in brain, skeletal muscle, kidney and heart. http://togogenome.org/gene/10090:Il9r ^@ http://purl.uniprot.org/uniprot/Q01114 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the type I cytokine receptor family. Type 4 subfamily.|||Cell membrane|||Interacts with IL9.|||Plays an important role in the immune response against parasites by acting as a receptor of IL9.|||Secreted|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation. http://togogenome.org/gene/10090:Tox3 ^@ http://purl.uniprot.org/uniprot/Q80W03 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Interacts (via HGM box) with CITED1 (via C-terminus); the interaction increases estrogen-response element (ERE)-dependent transcription and protection against cell death. Interacts with CREB1 (phosphorylated form). Interacts with CREB1; the interaction is not depolarization dependent. Interacts with CREBBP (via C-terminus) (By similarity).|||Nucleus|||The N-terminus is absolutely necessary for transactivation activity.|||Transcriptional coactivator of the p300/CBP-mediated transcription complex. Activates transactivation through cAMP response element (CRE) sites. Protects against cell death by inducing antiapoptotic and repressing pro-apoptotic transcripts. Stimulates transcription from the estrogen-responsive or BCL-2 promoters. Required for depolarization-induced transcription activation of the C-FOS promoter in neurons. Associates with chromatin to the estrogen-responsive C3 promoter region (By similarity).|||the C-terminus is required for calcium responsiveness but not for transactivation activity. http://togogenome.org/gene/10090:Rbmx ^@ http://purl.uniprot.org/uniprot/Q9WV02 ^@ Domain|||Function|||Induction|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Arg-182 is dimethylated, probably to asymmetric dimethylarginine.|||Both isoforms are widely expressed.|||By high-fructose diet.|||Homomultimer. Found in the supraspliceosome complex. Identified in the spliceosome C complex. Interacts with KHDRBS3. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, NCOA5 and PPP1CA Interacts with CLK2, KHDRBS2, SAFB, TRA2B and YTHDC1. Interacts with ERAP1; the interaction is RNA-independent (By similarity). Interacts with SAFB/SAFB1 (PubMed:19403048). Interacts with PPIA/CYPA (By similarity).|||Nucleus|||O-glycosylated.|||RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single-stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Also plays a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1-beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment.|||The RRM domain is necessary for RNA-binding, but not for splice site selection, indicating that its splicing activity does not require direct binding to RNA. http://togogenome.org/gene/10090:Cdt1 ^@ http://purl.uniprot.org/uniprot/Q8R4E9 ^@ Caution|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Cdt1 family.|||Interacts with GMNN; the interaction inhibits the binding of the MCM complex to origins of replication (PubMed:12192004, PubMed:15811859). Interacts with MCM6 (PubMed:15811859). Interacts with CDC6; are mutually dependent on one another for loading MCM complexes onto chromatin (By similarity). Interacts with PCNA (By similarity). Interacts with LRWD1 during G1 phase and during mitosis (By similarity). Interacts with NDC80 subunit of the NDC80 complex; leading to kinetochore localization (By similarity). Interacts with KAT7 (By similarity). Interacts with ubiquitin-binding protein FAF1; the interaction is likely to promote CDT1 degradation (By similarity).|||Nucleus|||Phosphorylation by cyclin A-dependent kinases at Thr-28 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. Phosphorylated at Thr-28 by MAPK8/JNK1, which blocks replication licensing in response to stress. Binding to GMNN is not affected by phosphorylation (PubMed:14993212).|||Present during G1 and early S phase of the cell cycle. Degraded during the late S, G2, and M phases.|||Required for both DNA replication and mitosis. DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC). Required also for mitosis by promoting stable kinetochore-microtubule attachments (By similarity). Potential oncogene (PubMed:11850834).|||The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.|||Two independent E3 ubiquitin ligase complexes, SCF(SKP2) and the DCX(DTL) complex, mediated CDT1 degradation in S phase. Ubiquitinated by the DCX(DTL) complex, in response to DNA damage, leading to its degradation. Ubiquitination by the DCX(DTL) complex is necessary to ensure proper cell cycle regulation and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Phosphorylation at Thr-28 by CDK2 targets CDT1 for ubiquitynation by SCF(SKP2) E3 ubiquitin ligase and subsequent degradation. The interaction with GMNN protects it against ubiquitination. Deubiquitinated by USP37.|||Was originally thought to have DNA binding activity (PubMed:12192004). However, more recent studies show that CDT1 binds DNA indirectly via ORC.|||kinetochore http://togogenome.org/gene/10090:Slc22a3 ^@ http://purl.uniprot.org/uniprot/Q547K2|||http://purl.uniprot.org/uniprot/Q9WTW5 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.|||Cell membrane|||Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.|||Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10966924, PubMed:18513366). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (By similarity). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, homovanillic acid, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:18513366, PubMed:19416912). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (By similarity). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (By similarity). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (By similarity). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (PubMed:27659446).|||Endomembrane system|||Highly expressed in placenta (PubMed:10966924, PubMed:9933568). Highly expressed in kidney cortex (PubMed:10966924). In kidney, expressed specifically in the proximal and distal convoluted tubules and within Bowman capsule (PubMed:10966924). Expressed in brain, particularly in dopaminergic neurons of the substantia nigra compacta, non-aminergic neurons of the ventral tegmental area, substantia nigra reticulata, locus coeruleus, hippocampus and cortex (PubMed:18513366). In brain, also detected in astrocytes in the substantia nigra reticulata, several hypothalamic nuclei and nigrostriatal region (PubMed:18513366, PubMed:19416912). Expressed in neurons and glial cells of amygdala (PubMed:27659446).|||Knockout mice show altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters. Knockout mice show subtle alterations in behaviors such as increased sensitivity to psychostimulants and increased levels of anxiety and stress (PubMed:18513366). Also exhibit impaired removal of the excess extracellular dopamine induced by methamphetamine and increased striatal dopaminergic terminal damage caused by this psychostimulant (PubMed:19416912).|||Levels are high during gestation, but decrease greatly towards the end of gestation.|||Mediates the uptake of clinically used drugs including neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) and platinum-based drug oxaliplatin (PubMed:10966924, PubMed:18513366, PubMed:19416912). Plays a role in the anticancer activity of oxaliplatin and may contribute to antitumor specificity (By similarity).|||Mitochondrion membrane|||Nucleus membrane|||Nucleus outer membrane http://togogenome.org/gene/10090:Ptn ^@ http://purl.uniprot.org/uniprot/P63089 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pleiotrophin family.|||Enhanced up to 3 days after the administration of chorionic gonadotropin to induce ovulation (PubMed:17121547). Up-regulated by progesterone in the uterine stromal cells through cAMP (PubMed:28657144).|||Homozygous PTN knockout mice are viable and fertile and show no gross anatomical abnormalities. The hippocampal structure as well as basal excitatory synaptic transmission in the area CA1 appear normal. The skeletal structure of homozygous PTN knockout mice develops normally. However, a growth retardation of the weight-bearing bones is observed by 2 months of age. Adult homozygous PTN knockout mice are characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling (PubMed:11414790, PubMed:12093164). Mice show faster learning in water maze and decreased anxiety in elevated plus-maze test (PubMed:12093164). Homozygous PTN knockout mice exhibit cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral entorhinal cortex, are normal (PubMed:25000129). PTN and MDK double knockout mice are born in only one third the number expected by Mendelian segregation and 4 weeks after birth weigh about half as much as wild-type mice. Most of the female are infertile. Both male and female one-month-old mice show a defect in spontaneous locomotive activity of 50-60% of that of wild-type mice. Although the difference in activity decrease with age, the activity of 3-month-old male double knockout mice is still about 80% of that of the wild-type mice. The diestrus and proestrus periods are long and the estrus period is short. Furthermore, vaginal abnormality is found in about half of the double deficient mice (PubMed:17121547). PTN and MDK double knockout mice have a deficit of auditory response (PubMed:16619002).|||Interacts with ALK and NEK6. Interacts with PTPRZ1 (via chondroitin sulfate groups); promotes formation of homooligomers; oligomerization impairs tyrosine phosphatase activity. Forms a complex with PTPRZ1 and CTNNB1; this complex inactivates PTPRZ1 protein tyrosine phosphatase activity through PTN interaction and stimulates tyrosine phosphorylation of CTNNB1. Interacts with ITGB3 and ITGA5. Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through ITGB3 'Tyr-773' phosphorylation (By similarity). Interacts with SDC3 (via heparan sulfate chains); this interaction mediates the neurite outgrowth-promoting signal from PTN to the cytoskeleton of growing neurites; this interaction mediates osteoblast recruitment. Interacts with GPC2 (via heparan sulfate); this interaction promotes neurite outgrowth through binding of PTN with chondroitin sulfate of proteoglycans, thereby releasing PTPRS of chondroitin sulfate proteoglycans (CSPGs) and leading to binding with heparan sulfate of GPC2 (By similarity).|||NoT detected in the uteri from days 1-3 of pregnancy. On day 4 of pregnancy, localizes in the luminal and glandular epithelium as well as in the uterine stromal cells. On day 5, a high level is observed in the subluminal stroma surrounding the implanting blastocyst, while there is no expression at the inter-implantation sites. From day 6-8 of pregnancy, strongly expressed in the decidua. Expression is gradually increased as the progression of pregnancy and reached a maximum on day 8. Elevated expression is observed at implantation sites from days 5-8 of pregnancy.|||Osteoblast and brain (PubMed:1701634, PubMed:1768439). Expressed in the follicular epithelium and granulosa cells of the ovary. Strongly expressed in the uterus of newborn mice, and the degree of expression decreased in one-week-old mice, although the expression continues even in the uteri of adult mice. Expression gradually increases from proestrus to estrus, then decreases sharply, and thereafter gradually increased again (PubMed:17121547). strongly expressed in the cochlea of WT mice 1 week after birth, and then the expression decreased and was undetectable by week 8 after birth (PubMed:16619002). Expressed around the cell soma of osteocytes and apparently captured in the unmineralized interstitial matrix surrounding the cells. Furthermore distributed throughout the intraosseous canalicular porosity, being localized in the unmineralized matrix around the cell processes. Strongly expressed in the innermost layer of the periosteum (PubMed:19442624).|||Phosphorylated by NEK6.|||Secreted|||Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors (By similarity). Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups (By similarity). Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration in several tissues namely neuron and bone (PubMed:15121180, PubMed:30497772, PubMed:27445335, PubMed:19442624). Also plays a role in synaptic plasticity and learning-related behavior by inhibiting long-term synaptic potentiation (PubMed:11414790, PubMed:25000129). Binds PTPRZ1, leading to neutralization of the negative charges of the CS chains of PTPRZ1, inducing PTPRZ1 clustering, thereby causing the dimerization and inactivation of its phosphatase activity leading to increased tyrosine phosphorylation of each of the PTPRZ1 substrates like ALK or AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:27445335). Through PTPRZ1 binding controls oligodendrocyte precursor cell differentiation by enhancing the phosphorylation of AFAP1L2 in order to activate the PI3K-AKT pathway (PubMed:27445335). Forms a complex with PTPRZ1 and integrin alpha-V/beta-3 (ITGAV:ITGB3) that stimulates endothelial cell migration through SRC dephosphorylation and activation that consequently leads to ITGB3 'Tyr-773' phosphorylation (By similarity). In adult hippocampus promotes dendritic arborization, spine development, and functional integration and connectivity of newborn granule neurons through ALK by activating AKT signaling pathway (PubMed:30497772). Binds GPC2 and chondroitin sulfate proteoglycans (CSPGs) at the neuron surface, leading to abrogation of binding between PTPRS and CSPGs and neurite outgrowth promotion (By similarity). Binds SDC3 and mediates bone formation by recruiting and attaching osteoblasts/osteoblast precursors to the sites for new bone deposition (By similarity). Binds ALK and promotes cell survival and cell proliferation through MAPK pathway activation (By similarity). Inhibits proliferation and enhances differentiation of neural stem cells by inhibiting FGF2-induced fibroblast growth factor receptor signaling pathway (PubMed:15121180). Mediates regulatory mechanisms in normal hemostasis and in hematopoietic regeneration and in maintaining the balance of myeloid and lymphoid regeneration (PubMed:21791434). In addition may play a role in the female reproductive system, auditory response and the progesterone-induced decidualization pathway (PubMed:17121547, PubMed:28657144, PubMed:16619002). http://togogenome.org/gene/10090:Bola2 ^@ http://purl.uniprot.org/uniprot/Q8BGS2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins. Acts together with the monothiol glutaredoxin GLRX3.|||Belongs to the BolA/IbaG family.|||Cytoplasm|||Interacts with GLRX3; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters.|||Nucleus http://togogenome.org/gene/10090:St6galnac3 ^@ http://purl.uniprot.org/uniprot/Q544M3|||http://purl.uniprot.org/uniprot/Q9WUV2 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 29 family.|||Golgi apparatus membrane|||In adult tissues, high expression in brain, lung and heart and to a lesser extent in kidney, mammary gland, spleen, testis and thymus.|||In brain, expression reaches maximum levels at day 12 of the embryonic stage. Keeps almost similar levels during mouse development.|||Membrane|||Transfers the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of glycoproteins and glycolipids forming an alpha-2,6-linkage. Produces branched type disialyl structures by transfer of a sialyl group onto a GalNAc residue inside the backbone core chains. ST6GalNAcIII prefers glycolipids to glycoproteins, predominantly catalyzing the biosynthesis of ganglioside GD1alpha from GM1b (PubMed:10207017, PubMed:10601645). GD1alpha is a critical molecule in the communication and interaction between neuronal cells and their supportive cells, particularly in brain tissues, and functions as an adhesion molecule in the process of metastasis (By similarity). Sialylation of glycoproteins or glycosphingolipids is very important in tumor development, neuronal development, nerve repair, immunological processes and regulation of hormone sensitivity (By similarity). http://togogenome.org/gene/10090:Gpr61 ^@ http://purl.uniprot.org/uniprot/Q8C010 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Deficient mice exhibit obesity associated with hyperphagia.|||Endosome membrane|||Forms heterodimer with MTNR1B. Interacts with ARRB1 and ARRB2 in a spontaneous and agonist-independent manner; leading to the internalization of GPR61 in the endosomal compartment (By similarity).|||Orphan G-protein coupled receptor. Constitutively activates the G(s)-alpha/cAMP signaling pathway (By similarity). Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization (By similarity). May be involved in the regulation of food intake and body weight (PubMed:21971119).|||Predominantly expressed in the brain and testes, with relatively lower expression observed in the eye, adrenal gland and pituitary gland. http://togogenome.org/gene/10090:Rfc1 ^@ http://purl.uniprot.org/uniprot/A0A0N5E9G7|||http://purl.uniprot.org/uniprot/G3X8Z6|||http://purl.uniprot.org/uniprot/P35601|||http://purl.uniprot.org/uniprot/Q5U4B1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Alternative use of an acceptor site.|||Belongs to the activator 1 large subunit family.|||Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA (By similarity).|||Nucleus|||The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins PCNA and activator 1. This subunit binds to the primer-template junction. http://togogenome.org/gene/10090:Ltbp1 ^@ http://purl.uniprot.org/uniprot/Q8CG19 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the LTBP family.|||Contains hydroxylated asparagine residues.|||Interacts with TGFB1; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1. LTBP1 does not bind directly to TGF-beta-1, the active chain of TGFB1. Interacts (via C-terminal domain) with FBN1 (via N-terminal domain). Interacts with FBN2. Interacts with ADAMTSL2. Interacts with EFEMP2 (By similarity).|||Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta. Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta.|||O-glycosylated on serine residues by POGLUT2 and POGLUT3.|||Secreted|||The 8-Cys3 region in the third TB domain mediates the interchain disulfide bond interaction with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1.|||Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Nrk ^@ http://purl.uniprot.org/uniprot/Q9R0G8 ^@ Developmental Stage|||Function|||Sequence Caution|||Similarity ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Contaminating sequence. Potential poly-A sequence.|||May phosphorylate cofilin-1 and induce actin polymerization through this process, during the late stages of embryogenesis. Involved in the TNF-alpha-induced signaling pathway.|||Predominantly expressed in skeletal muscle during embryogenesis. Expression was detected in the myotome at 10.5 dpc and, thereafter, was observed in developing skeletal musculature from 11.5 to 13.5 dpc and increased from 15 to 17 dpc. However, expression in skeletal muscle was not observed in adults. Its expression may be down-regulated as development proceeds. http://togogenome.org/gene/10090:Tubgcp5 ^@ http://purl.uniprot.org/uniprot/Q8BKN5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TUBGCP family.|||Gamma-tubulin complex is composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6.|||Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.|||centrosome http://togogenome.org/gene/10090:Kcnrg ^@ http://purl.uniprot.org/uniprot/Q2TUM3 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Can form homooligomers. Interacts with KCNA1 (via cytoplasmic N-terminal domain) and KCNA4.|||Endoplasmic reticulum|||Inhibits potassium fluxes in cells. May regulate Kv1 family channel proteins by retaining a fraction of channels in endomembranes (By similarity). http://togogenome.org/gene/10090:Lpxn ^@ http://purl.uniprot.org/uniprot/Q99N69 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the paxillin family.|||Cell membrane|||Cytoplasm|||Expressed in osteoclasts (at protein level). Highly expressed in vascular smooth muscle.|||Interacts with unphosphorylated ITGA4. Interacts with AR and SRF (By similarity). Interacts with PTK2B/PYK2, PTPN22 and PTPN12. Interacts (via LD motif 3) with LYN and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via LD motif 3) with PTK2/FAK.|||Nucleus|||Phosphorylated on tyrosine residues. Phosphorylation on Tyr-72 is important for its inhibitory function. Bombesin stimulates phosphorylation on Tyr-22, Tyr-62 and Tyr-72 (By similarity).|||The LIM domain 3 is critical for focal adhesion targeting and the suppression of paxillin (PXN) tyrosine phosphorylation. The LIM domain 3 alone or both LIM domains 3 and 4 can mediate interaction with AR.|||Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in integrin-mediated cell adhesion events. Suppresses the integrin-induced tyrosine phosphorylation of paxillin (PXN). May play a critical role as an adapter protein in the formation of the adhesion zone in osteoclasts. Negatively regulates B-cell antigen receptor (BCR) signaling.|||focal adhesion|||perinuclear region|||podosome http://togogenome.org/gene/10090:Arl5a ^@ http://purl.uniprot.org/uniprot/Q498A0|||http://purl.uniprot.org/uniprot/Q80ZU0 ^@ Function|||Similarity ^@ Belongs to the small GTPase superfamily. Arf family.|||Lacks ADP-ribosylation enhancing activity. http://togogenome.org/gene/10090:Farsb ^@ http://purl.uniprot.org/uniprot/Q9CZU5|||http://purl.uniprot.org/uniprot/Q9WUA2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.|||Cytoplasm|||Heterotetramer; dimer of two heterodimers formed by FARSA and FARSB. http://togogenome.org/gene/10090:Kmt5a ^@ http://purl.uniprot.org/uniprot/A0A0G2JFK5|||http://purl.uniprot.org/uniprot/D3YXI6|||http://purl.uniprot.org/uniprot/E9QNB8|||http://purl.uniprot.org/uniprot/Q2YDW7 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.|||Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.|||Chromosome|||Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates KMT5A-mediated methyltransferase activity at histone H4 'Lys-20' (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner (By similarity).|||Nucleus|||Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration.|||Ubiquitinated and degraded by the DCX(DTL) complex. http://togogenome.org/gene/10090:Celsr1 ^@ http://purl.uniprot.org/uniprot/O35161 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.|||Cell membrane|||Expressed in the brain, where it is localized principally in the ependymal cell layer, choroid plexus and the area postrema. Also found in spinal cord and in the eye.|||First detected at 6 dpc. Predominantly expressed in the developing CNS, the emerging dorsal root ganglia and cranial ganglia. In the CNS, expression is uniform along the rostrocaudal axis. During gastrulation, it is expressed in the vicinity of the primitive streak, and becomes predominant in that area at late gastrulation. At 10 dpc, detected in ventricular zones (VZ), but not in marginal zones (MZ), and weakly in other structures. Between 12 dpc and 15 dpc, a high expression is present in the VZ in all brain areas. No expression in differentiated neuronal fields. In the newborn and postnatal stages, expression remains restricted to the VZ. Also found weakly in fetal lungs, kidney and epithelia.|||Receptor that may have an important role in cell/cell signaling during nervous system formation.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Tgif1 ^@ http://purl.uniprot.org/uniprot/G3UWC5|||http://purl.uniprot.org/uniprot/P70284|||http://purl.uniprot.org/uniprot/Q3TVD4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TALE/TGIF homeobox family.|||Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities (By similarity).|||Interacts with SMAD2 (By similarity). Interacts with CTBP, SMAD3 and HDAC1.|||Nucleus http://togogenome.org/gene/10090:Izumo1 ^@ http://purl.uniprot.org/uniprot/Q9D9J7 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Izumo family.|||Cell membrane|||Essential sperm cell-surface protein required for fertilization by acting as a ligand for IZUMO1R/JUNO receptor on egg (PubMed:15759005, PubMed:24739963, PubMed:27309808). The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion (PubMed:15759005, PubMed:24739963, PubMed:27309808). The ligand-receptor interaction probably does not act as a membrane 'fusogen' (PubMed:15759005, PubMed:24739963, PubMed:27309808).|||Izumo is the name of a Japanese shrine to marriage.|||Mice are healthy but the males are sterile (PubMed:15759005). They produce morphologically normal sperm that can bind to and penetrate the zona pellucida but that are incapable of fusing with eggs (PubMed:15759005).|||Monomer, homodimer and homooligomer; depending on the context (PubMed:19658160, PubMed:26568141, PubMed:29954238). Interacts with IZUMO1R/JUNO (PubMed:25209248, PubMed:24739963, PubMed:27309808, PubMed:32484434). IZUMO1 and IZUMO1R/JUNO form a complex with 1:1 stoichiometry (By similarity). In gamete recognition, IZUMO1R/JUNO first binds to monomeric IZUMO1 (PubMed:26568141, PubMed:29954238). The weak, but specific interaction with IZUMO1R/JUNO induces IZUMO1 homodimerization (PubMed:26568141, PubMed:29954238). The process follows a tight binding phase where IZUMO1 bends the entire structure towards the sperm membrane side through a thiol-disulfide exchange reaction (PubMed:26568141, PubMed:29954238). The molecule no longer binds to IZUMO1R/JUNO and instead binds to a putative second oocyte receptor (PubMed:26568141, PubMed:29954238). Interacts with ACE3 (PubMed:20421979, PubMed:35960805, PubMed:19658160, PubMed:24739963, PubMed:25209248, PubMed:26568141, PubMed:27309808, PubMed:29954238) (By similarity). Part of a oolemmal binding multimeric complex (IZUMO1 complex) composed at least of IZUMO1 and GLIPR1L1; the complex assemblage is influenced by the maturation status of the male germ cell (PubMed:31672133). Interacts with GLIPR1L1 (PubMed:31672133). Interacts with FREY; the interaction retains IZUMO1 at the endoplasmic reticulum membrane and coordinates IZUMO1 complex assembly (PubMed:35960805).|||N-glycosylated. Glycosylation is not essential for fusion and for proper protein trafficking in sperm.|||Partially colocalizes with FREY1 in endoplasmic reticulum membrane of round spermatids.|||Phosphorylated (PubMed:19658160, PubMed:27624483). The cytoplasmic C-terminus is phosphorylated and undergoes phosphorylation changes during epididymal transit (PubMed:27624483).|||Sperm-specific (at protein level) (PubMed:15759005, PubMed:19658160, PubMed:20421979, PubMed:32484434, PubMed:35960805, PubMed:31672133). Detectable on sperm surface only after the acrosome reaction (PubMed:15759005).|||The cytoplasmic C-terminus region is not essential for fertilization (PubMed:27624483). It is however required for protein stability (PubMed:27624483).|||The extracellular domain assumes a distinct boomerang shape when not bound to IZUMO1R/JUNO (By similarity). Interaction with IZUMO1R/JUNO triggers a conformation change, so that the IZUMO1 extracellular domain assumes an upright conformation (By similarity).|||acrosome membrane http://togogenome.org/gene/10090:Eif1a ^@ http://purl.uniprot.org/uniprot/Q4FJR7|||http://purl.uniprot.org/uniprot/Q60872 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1.|||Component of the 43S pre-initiation complex (43S PIC), which is composed of the 40S ribosomal subunit, EIF1, eIF1A (EIF1AX), eIF3 complex, EIF5 and eIF2-GTP-initiator tRNA complex (eIF2 ternary complex). Interacts with EIF5; this interaction contributes to the maintenance of EIF1 within the open 43S PIC. Interacts through its C-terminal domain (CTD) with the CTD of EIF5B; from the location of the start codon by the 43S complex until the formation of the 80S complex.|||Cytoplasm http://togogenome.org/gene/10090:Prss16 ^@ http://purl.uniprot.org/uniprot/Q5SZ30|||http://purl.uniprot.org/uniprot/Q9QXE5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the peptidase S28 family.|||Cytoplasmic vesicle|||Expressed in developing thymus at 14 to 18 dpc, with maximal expression at 16 dpc.|||Expressed predominantly in cortical thymic epithelial cells, with highest expression around vessels and the thymic capsule.|||Protease that may play a role in T-cell development. http://togogenome.org/gene/10090:Adamts16 ^@ http://purl.uniprot.org/uniprot/Q69Z28 ^@ Cofactor|||Domain|||PTM|||Subcellular Location Annotation ^@ Binds 1 zinc ion per subunit.|||Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||The precursor is cleaved by a furin endopeptidase.|||The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.|||extracellular matrix http://togogenome.org/gene/10090:Naa20 ^@ http://purl.uniprot.org/uniprot/P61600 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the acetyltransferase family. ARD1 subfamily.|||Catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. Proteins with cell cycle functions are overrepresented in the pool of NatB substrates. Required for maintaining the structure and function of actomyosin fibers and for proper cellular migration.|||Component of the N-terminal acetyltransferase B (NatB) complex which is composed of NAA20 and NAA25.|||Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Pold2 ^@ http://purl.uniprot.org/uniprot/O35654 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex. As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS as a component of the DNA polymerase zeta complex. Along with POLD3, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7.|||Belongs to the DNA polymerase delta/II small subunit family.|||Component of both the DNA polymerase delta and DNA polymerase zeta complexes. Component of the tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities. Within Pol-delta4, directly interacts with POLD1, POLD3 and POLD4. Following stress caused by DNA damaging agents or by replication stress, POLD4 is degraded and Pol-delta4 is converted into a trimeric form of the complex (Pol-delta3), which consists of POLD1, POLD2 and POLD3. Pol-delta3 is the major form occurring at S phase replication sites, as well as DNA damage sites. Also observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol-delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by over 50-fold. Contrary to the other components of Pol-delta4, does not directly interact with PCNA. As POLD1 and POLD4, directly interacts with WRNIP1; this interaction stimulates DNA polymerase delta-mediated DNA synthesis, independently of the presence of PCNA. This stimulation may be due predominantly to an increase of initiation frequency and also to increased processivity. Directly interacts with POLDIP2 and POLDIP3. Directly interacts with KCTD13/PDIP1; in the presence of PCNA, this interaction may stimulate DNA polymerase activity. Component of the tetrameric Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3, with REV3L bearing DNA polymerase catalytic activity (By similarity). Interacts with KCTD10 (By similarity).|||Nucleus http://togogenome.org/gene/10090:Bhlhb9 ^@ http://purl.uniprot.org/uniprot/Q6PB60 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GPRASP family.|||Cytoplasm|||Despite its name, no basic helix-loop-helix (bHLH) domain is detected by any prediction tool.|||Homodimer.|||Nucleus|||Survival and differentiation promoting protein that plays a role in the regulation of neurosynaptogenesis. Induces phosphatase PP2A activity which results in APP dephosphorylation and inhibits BACE1-mediated processing of APP. http://togogenome.org/gene/10090:Sec23b ^@ http://purl.uniprot.org/uniprot/Q3TIS3|||http://purl.uniprot.org/uniprot/Q8CDS4|||http://purl.uniprot.org/uniprot/Q9D662 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SEC23/SEC24 family. SEC23 subfamily.|||COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1 (By similarity). Interacts with SAR1A (By similarity).|||COPII-coated vesicle membrane|||Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex.|||Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules.|||Endoplasmic reticulum membrane|||Membrane|||cytosol http://togogenome.org/gene/10090:Hprt ^@ http://purl.uniprot.org/uniprot/P00493 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the purine/pyrimidine phosphoribosyltransferase family.|||Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein.|||Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway (By similarity).|||Cytoplasm|||Homotetramer. http://togogenome.org/gene/10090:Inppl1 ^@ http://purl.uniprot.org/uniprot/Q6P549 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated upon translocation to the sites of synthesis of PtdIns(3,4,5)P3 in the membrane. Enzymatic activity is enhanced in the presence of phosphatidylserine (By similarity).|||Basal cell membrane|||Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.|||In 15.5 dpc embryos, it is strongly expressed in the liver, specific regions of the central nervous system, the thymus, the lung, and the cartilage perichondrium. In adult it is markedly present in the brain and the thymus and at different stages of spermatozoa maturation in the seminiferous tubules.|||Interacts with tyrosine phosphorylated form of SHC1 (By similarity). Interacts with EGFR (By similarity). Upon stimulation by the EGF signaling pathway, it forms a complex with SHC1 and EGFR (By similarity). Interacts with cytoskeletal protein SORBS3/vinexin, promoting its localization to the periphery of cells (By similarity). Forms a complex with filamin (FLNA or FLNB), actin, GPIb (GP1BA or GP1BB) that regulates cortical and submembraneous actin (By similarity). Interacts with c-Met/MET, when c-Met/MET is phosphorylated on 'Tyr-1356' (By similarity). Interacts with p130Cas/BCAR1 (By similarity). Interacts with CENTD3/ARAP3 via its SAM domain (By similarity). Interacts with c-Cbl/CBL and CAP/SORBS1 (By similarity). Interacts with activated EPHA2 receptor (PubMed:29749928). Interacts with receptors FCGR2A (By similarity). Interacts with FCGR2B (PubMed:10789675, PubMed:15456754). Interacts with tyrosine kinase ABL1 (By similarity). Interacts with tyrosine kinase TEC (PubMed:15492005). Interacts with CSF1R (PubMed:15557176). Interacts (via N-terminus) with SH3YL1 (via SH3 domain) (PubMed:21624956). Interacts (via SH2 domain) with tyrosine phosphorylated KLRC1 (via ITIM) (PubMed:9485206). Interacts with NEDD9/HEF1 (By similarity).|||Membrane|||Mice are viable, have normal glucose and insulin levels, and normal insulin and glucose tolerance. They are however highly resistant to weight gain when placed on a high-fat diet, suggesting that inhibition of Inppl1 would be useful in the effort to ameliorate diet-induced obesity. According to preliminary results from PubMed:11343120, mice display increased sensitivity to insulin, characterized by severe neonatal hypoglycemia, deregulated expression of the genes involved in gluconeogenesis, and perinatal death. They display increased glucose tolerance and insulin sensitivity associated with an increased recruitment of the Slc2a4/Glut4 glucose transporter and increased glycogen synthesis in skeletal muscles. However, these knockout mice also contain a deletion of the last exon of Phox2a gene. It is therefore unknown whether the insulin sensitivity observed in these mice result from inactivation of either Inppl1 or Phox2a.|||Nucleus|||Nucleus speckle|||Overexpressed in diabetic db/db mice.|||Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:10958682). Required for correct mitotic spindle orientation and therefore progression of mitosis (By similarity). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (PubMed:11343120). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (PubMed:14744864). Confers resistance to dietary obesity (PubMed:15654325). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane (PubMed:14744864). Part of a signaling pathway that regulates actin cytoskeleton remodeling (By similarity). Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation (By similarity). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (By similarity). Regulates cell adhesion and cell spreading (PubMed:29749928). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (By similarity). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (By similarity). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (By similarity). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (PubMed:10789675, PubMed:15456754). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (By similarity). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (By similarity). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (PubMed:15557176, PubMed:16179375). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (PubMed:15557176, PubMed:16179375). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (By similarity). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (By similarity). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (By similarity). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (By similarity).|||The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain.|||The SH2 domain interacts with tyrosine phosphorylated forms of proteins such as SHC1 or FCGR2A (By similarity). It also mediates the interaction with p130Cas/BCAR1 (By similarity).|||Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as insulin, growth factors such as EGF or PDGF, chemokines, integrin ligands and hypertonic and oxidative stress. May be phosphorylated upon IgG receptor FCGR2B-binding. Phosphorylated at Tyr-987 following cell attachment and spreading. Phosphorylated at Tyr-1161 following EGF signaling pathway stimulation (By similarity).|||Widely expressed.|||cytoskeleton|||cytosol|||filopodium|||lamellipodium|||spindle pole http://togogenome.org/gene/10090:Paip2b ^@ http://purl.uniprot.org/uniprot/A0A158RFV3|||http://purl.uniprot.org/uniprot/Q91W45 ^@ Caution|||Function|||PTM|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the PAIP2 family.|||Expressed at very high levels in pancreas, at high levels in testis and at moderately high levels in brain, heart and lung (at protein level).|||Inhibits translation of capped and polyadenylated mRNAs by displacing PABPC1 from the poly(A) tail.|||Interacts (via central acidic portion and C-terminus) with PABPC1 (via the second and third RRM domains and the C-terminus).|||It is uncertain whether Met-1 or Met-14 is the initiator.|||Ubiquitinated in vitro. http://togogenome.org/gene/10090:Alpi ^@ http://purl.uniprot.org/uniprot/F8VPQ6 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the alkaline phosphatase family.|||Binds 1 Mg(2+) ion.|||Binds 2 Zn(2+) ions.|||Cell membrane|||Homodimer.|||Membrane http://togogenome.org/gene/10090:Rab32 ^@ http://purl.uniprot.org/uniprot/Q0PD23|||http://purl.uniprot.org/uniprot/Q9CZE3 ^@ Activity Regulation|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and Mycobacterium (By similarity). Plays an important role in the control of melanin production and melanosome biogenesis (By similarity). In concert with RAB38, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (PubMed:26620560).|||Belongs to the small GTPase superfamily. Rab family.|||In the embryo, highest levels occur at day 7.|||Interacts with ANKRD27 (PubMed:19403694, PubMed:21187289). A decreased interaction with ANKRD27 seen in the presence of SGSM2 (By similarity).|||Melanosome|||Melanosome membrane|||Membrane|||Mitochondrion|||Mitochondrion outer membrane|||Regulated by a guanine nucleotide-exchange factor (GEF) and a GTPase-activating protein (GAP) and alternates between an inactive GDP-bound and an active GTP-bound form. The BLOC-3 complex composed of HPS1 and HPS4 acts as its GEF, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form. SGSM2 acts as its GAP and inactivates it by stimulating its GTPase activity (PubMed:26620560).|||The small GTPases Rab are key regulators in vesicle trafficking.|||Widely expressed with highest levels in liver. Strong expression also found in melanocyte, platelet, mast cell and fibroblast cell lines.|||phagosome|||phagosome membrane http://togogenome.org/gene/10090:Or8b51 ^@ http://purl.uniprot.org/uniprot/Q8VG53 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plcd1 ^@ http://purl.uniprot.org/uniprot/G5DDB7|||http://purl.uniprot.org/uniprot/Q8R3B1 ^@ Cofactor|||Disruption Phenotype|||Function|||Subunit|||Tissue Specificity ^@ Binds 3 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.|||Binds 5 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.|||Highly expressed in brain, heart, lung, epididymis and testis. Detected at lower levels in kidney and skeletal muscle.|||Interacts with TGM2.|||Mice lacking Plcd1 and Plcd3 die between 11.5 and 13.5 dpc. They exhibit severe disruption of the normal labyrinth architecture in the placenta and decreased placental vascularization, as well as abnormal proliferation and apoptosis of trophoblasts in the labyrinth area. Furthermore, Plcd1 and Plcd3 double knockout embryos supplied with a normal placenta by the tetraploid aggregation method survive beyond 14.5 dpc, indicating that the embryonic lethality is caused by a defect in trophoblasts.|||The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. Essential for trophoblast and placental development. Binds phosphatidylinositol 4,5-bisphosphate (By similarity). http://togogenome.org/gene/10090:Fgfbp1 ^@ http://purl.uniprot.org/uniprot/O70514 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a carrier protein that releases fibroblast-binding factors (FGFs) from the extracellular matrix (EM) storage and thus enhances the mitogenic activity of FGFs. Enhances FGF2 signaling during tissue repair, angiogenesis and in tumor growth (By similarity).|||Belongs to the fibroblast growth factor-binding protein family.|||Cell membrane|||Expressed in digestive system, skin, hair follicles, the dental germ, respiratory tract, various glandular tissues, kidney, liver and certain areas of the central nervous system between 8 and 16 dpc (at protein level). Expressed. in embryo between 9 to 18 dpc. Expressed at 14 dpc in the epithelial cells and 18 dpc in basal epithelial cells of intestinal crypts. Expressed in mesenchymal and epidermal structures of the body wall at 9 dpc. Expressed in basal cells of the subepidermal layer of the skin at 12 dpc. Expressed in hair follicles at 14 dpc.|||Expressed in intestine, ovary, lung, placenta and normal and wounded skin.|||Expression is significantly up-regulated in skin papillomas and carcinomas.|||Found in a complex with FGFBP1, FGF1 and FGF2. Interacts with FGF1, FGF7, FGF10, FGF22 and HSPG2 (By similarity). Interacts with FGF2.|||extracellular space http://togogenome.org/gene/10090:Daam1 ^@ http://purl.uniprot.org/uniprot/Q8BPM0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the formin homology family.|||Binds to disheveled (Dvl) and Rho, and mediates Wnt-induced Dvl-Rho complex formation. May play a role as a scaffolding protein to recruit Rho-GDP and Rho-GEF, thereby enhancing Rho-GTP formation. Can direct nucleation and elongation of new actin filaments (By similarity). Involved in building functional cilia. Involved in the organization of the subapical actin network in multiciliated epithelial cells (By similarity). Together with DAAM2, required for myocardial maturation and sarcomere assembly (PubMed:26526197).|||Conditional knockout mice lacking Daam1 in myocardial cells show cardiomyopathy. Conditional knockout mice lacking Daam1 and Daam2 in myocardial cells show stronger cardiomyopathy.|||Cytoplasm|||Detected throughout the myocardial layer of the heart tube. Not expressed in the myocardium at 9.5 dpc but is present in epicardial cells and the pro-epicardial organ. At 10.5 dpc, expressed in the atrial and ventricular myocardia as well as the inter-ventricular septum. Continues to localize to the atrial and ventricular myocardia at 12.5 dpc as well as the ventricular trabeculae.|||In early embryogenesis, expressed in embryonic and extraembryonic ectoderm. In later stages of gastrulation, expressed also in somites and ribs and posterior vertebrae of developing skeletal system. During organogenesis, expressed in CNS, PNS, stomach, liver and limb bud.|||Interacts with CIP4, FNBP1 and FNBP1L. Interacts with the SH3 domains of Abl, BTK, endophilin, spectrin and SRC. Binds specifically to GTP-bound CDC42 and RHOA. Interacts with INTU; INTU mediates the indirect interaction between DAAM1 and NPHP4 (By similarity).|||The C-terminal DAD domain may participate in intramolecular interactions with the N-terminus.|||The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).|||cilium basal body http://togogenome.org/gene/10090:Slc28a2b ^@ http://purl.uniprot.org/uniprot/A2AWR5 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.|||Membrane http://togogenome.org/gene/10090:Zfp771 ^@ http://purl.uniprot.org/uniprot/Q8BJ90 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Cpt1b ^@ http://purl.uniprot.org/uniprot/Q924X2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the carnitine/choline acetyltransferase family.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Stn1 ^@ http://purl.uniprot.org/uniprot/Q3UXU8|||http://purl.uniprot.org/uniprot/Q8K2X3 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ According to PubMed:19119139, it acts as a regulator of DNA replication. According to PubMed:19854130, this effect is indirect and it rather acts as a general regulator of DNA metabolism.|||Belongs to the STN1 family.|||Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22748632). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins. Required for efficicient replication of the duplex region of the telomere. Promotes efficient replication of lagging-strand telomeres. Promotes general replication start following replication-fork stalling implicating new origin firing. May be in involved in C-strand fill-in during late S/G2 phase independent of its role in telomere duplex replication (By similarity).|||Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation. However, the CST complex has been shown to be involved in several aspects of telomere replication.|||Component of the CST complex, composed of TEN1/C17orf106, CTC1/C17orf68 and STN1; in the complex interacts directly with TEN1 and CTC1 (PubMed:19119139, PubMed:19854130). Interacts with ACD/TPP1 (PubMed:19648609). Interacts with POT1 and POLA1 (By similarity).|||Component of the CST complex.|||Nucleus|||telomere http://togogenome.org/gene/10090:Nudt22 ^@ http://purl.uniprot.org/uniprot/Q9DD16 ^@ Function|||Similarity ^@ Belongs to the Nudix hydrolase family.|||Hydrolyzes UDP-glucose to glucose 1-phosphate and UMP and UDP-galactose to galactose 1-phosphate and UMP. Preferred substrate is UDP-glucose. http://togogenome.org/gene/10090:Pdgfra ^@ http://purl.uniprot.org/uniprot/P26618 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-731 and Tyr-742 is important for interaction with PIK3R1. Phosphorylation at Tyr-720 and Tyr-754 is important for interaction with PTPN11. Phosphorylation at Tyr-762 is important for interaction with CRK. Phosphorylation at Tyr-572 and Tyr-574 is important for interaction with SRC and SRC family members. Phosphorylation at Tyr-988 and Tyr-1018 is important for interaction with PLCG1 (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.|||Cell membrane|||Embryonically lethal. Most embryos survive up to 13 dpc, but display important defects in skeleton development, including spina bifida, fusions of cervical vertebrae and ribs, and incomplete fusion of the skull parietal bone. Embryos display also abnormal mucosa lining the gastrointestinal tract, including fewer and misshapen villi and loss of pericryptal mesenchyme. At about 16 dpc, embryos display extensive hemorrhaging.|||Focally expressed in cortical interstitial cells and highly expressed in the interstitium of the papillary region. Also expressed by adventitial cells in arterial vessels. Up-regulated in areas of renal fibrosis. In mice with unilateral ureteral obstruction, expression in cortical interstitial cells becomes prominent at day 4 which increases progressively until day 14.|||Golgi apparatus|||Interacts with homodimeric PDGFA, PDGFB and PDGFC, and with heterodimers formed by PDGFA and PDGFB. Monomer in the absence of bound ligand. Interaction with dimeric PDGFA, PDGFB and/or PDGFC leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts (tyrosine phosphorylated) with SHB (via SH2 domain). Interacts (tyrosine phosphorylated) with SHF (via SH2 domain). Interacts (tyrosine phosphorylated) with SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1. Interacts (tyrosine phosphorylated) with PLCG1 (via SH2 domain). Interacts (tyrosine phosphorylated) with CRK, GRB2 and GRB7 (By similarity).|||Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib, nilotinib and sorafenib (By similarity).|||Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor.|||Ubiquitinated, leading to its internalization and degradation.|||Up-regulated by growth arrest.|||cilium http://togogenome.org/gene/10090:Clrn1 ^@ http://purl.uniprot.org/uniprot/B7ZNE8|||http://purl.uniprot.org/uniprot/Q8BYX9|||http://purl.uniprot.org/uniprot/Q8K444|||http://purl.uniprot.org/uniprot/Q8K445 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the clarin family.|||Cell membrane|||May have a role in the excitatory ribbon synapse junctions between hair cells and cochlear ganglion cells and presumably also in analogous synapses within the retina.|||Membrane http://togogenome.org/gene/10090:Or4a70 ^@ http://purl.uniprot.org/uniprot/Q8VGM6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Themis3 ^@ http://purl.uniprot.org/uniprot/Q9CU24 ^@ Similarity|||Tissue Specificity ^@ Belongs to the themis family.|||Specifically expressed in the intestine. http://togogenome.org/gene/10090:Casp6 ^@ http://purl.uniprot.org/uniprot/O08738|||http://purl.uniprot.org/uniprot/Q3TPJ9 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Proteolytically cleaves the N protein of coronoviruses. The cleavage leads to two fragments and modulates coronavirus replication by regulating IFN signaling. The two fragments produced by the cleavage interact with IRF3 inhibiting its nuclear translocation after activation and reduce the expression of IFNB and IFN-stimulated genes.|||Belongs to the peptidase C14A family.|||Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-162 and Asp-175, while it is not able to cleave its N-terminal disordered prodomain. Cleaved and activated by CASP1, possibly in the context of inflammation.|||Casp6-knockout mice are grossly normal, breed with Mendelian ratio, and are only slightly protected from anti-Fas/CD95-induced cell death (PubMed:11062535). Casp6-deficient neurons undergo apoptosis and exhibit soma and axon degeneration just as wild type neurons (PubMed:23695670). While Casp6-deficiency is able to block axon degeneration with local deprivation, it is incapable of doing so with global deprivation (PubMed:23695670). In addition, B-cell differentiation into plasma cells is accelerated in deletion mutants compared to wild-type (PubMed:18981099, PubMed:29863787). Casp6-knockout mice are more susceptible to influenza virus infection (PubMed:32298652).|||Cysteine protease that plays essential roles in programmed cell death, axonal degeneration, development and innate immunity (PubMed:18981099, PubMed:22555455, PubMed:23695670, PubMed:32298652). Acts as a non-canonical executioner caspase during apoptosis: localizes in the nucleus and cleaves the nuclear structural protein NUMA1 and lamin A/LMNA thereby inducing nuclear shrinkage and fragmentation (By similarity). Lamin-A/LMNA cleavage is required for chromatin condensation and nuclear disassembly during apoptotic execution (By similarity). Acts as a regulator of liver damage by promoting hepatocyte apoptosis: in absence of phosphorylation by AMP-activated protein kinase (AMPK), catalyzes cleavage of BID, leading to cytochrome c release, thereby participating in nonalcoholic steatohepatitis (PubMed:32029622). Cleaves PARK7/DJ-1 in cells undergoing apoptosis (PubMed:22555455). Involved in intrinsic apoptosis by mediating cleavage of RIPK1 (By similarity). Furthermore, cleaves many transcription factors such as NF-kappa-B and cAMP response element-binding protein/CREBBP (By similarity). Cleaves phospholipid scramblase proteins XKR4 and XKR9 (PubMed:25231987). In addition to apoptosis, involved in different forms of programmed cell death (PubMed:32298652). Plays an essential role in defense against viruses by acting as a central mediator of the ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis), independently of its cysteine protease activity (PubMed:32298652). PANoptosis is a unique inflammatory programmed cell death, which provides a molecular scaffold that allows the interactions and activation of machinery required for inflammasome/pyroptosis, apoptosis and necroptosis (PubMed:32298652). Mechanistically, interacts with RIPK3 and enhances the interaction between RIPK3 and ZBP1, leading to ZBP1-mediated inflammasome activation and cell death (PubMed:32298652). Plays an essential role in axon degeneration during axon pruning which is the remodeling of axons during neurogenesis but not apoptosis (PubMed:23695670). Regulates B-cell programs both during early development and after antigen stimulation (PubMed:18981099, PubMed:29863787).|||Cytoplasm|||During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit. The two large and two small subunits then assemble to form the active CASP6 complex. Can be cleaved and activated by different caspases, depending on the context. Cleaved and activated by caspase-8 (CASP8) and subsequently by caspase-3 (CASP3). Can also undergo autoactivation by mediating autocleavage at Asp-162 and Asp-175, while it is not able to cleave its N-terminal disordered prodomain. Intramolecular cleavage at Asp-175 is a prerequisite for CASP6 self-activation. Cleaved and activated by CASP1 in neurons, possibly in the context of inflammation. Phosphorylation at Ser-239 inhibits autocleavage, preventing caspase activation.|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.|||Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit. Interacts with BIRC6/bruce. Interacts with RIPK3.|||Highly expressed in lung, liver, kidney, testis, and heart. Lower levels in spleen, skeletal muscle and brain. Expressed in neurons.|||Nucleus|||Palmitoylation by ZDHHC17 blocks dimerization and subsequent activation, leading to inhibit the cysteine protease activity.|||Phosphorylated by NUAK1; phosphorylation inhibits self-activation. Phosphorylation at Ser-239 by AMP-activated protein kinase (PRKAA1 or PRKAA2) inhibits autocleavage, preventing caspase activation, thereby preventing hepatocyte apoptosis.|||The N-terminal disordered prodomain is required to prevent self-activation.|||The Tri-arginine exosite is required to recruit substrates for hydrolysis.|||Undergoes helix-strand structural transitions upon substrate-binding: the 130's region interconverts between an inactive helical state and the canonically active strand state. Other caspases rest constitutively in the strand conformation before and after substrate-binding. http://togogenome.org/gene/10090:Lhx9 ^@ http://purl.uniprot.org/uniprot/Q9WUH2 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in the dorsal thalamus and inner nuclei of the cerebellum.|||Expressed in urogenital ridges of mice at 9.5 dpc. Expressed in the nervous system at 10.5 dpc. Expressed in the forelimb and hindlimb buds, the caelomic cavity at the level of the urogenital ridge, including the gonads, the pancreas and liver epithelium at 11.5 dpc. Expressed widespread throughout the CNS alar neuroepithelium from 11.5 to 14.5 dpc. Expressed in pioneer neurons of the cerebral cortex. In the telencephalic vesicles, expressed in cerebral cortex, the hippocampus, the claustrum primordium, olfactory bulb primordium and the caudal ganglionic eminence (amygdaloid complex) at 13.5 dpc. In the diencephalon, expressed in the pretectum (p1 prosomere), the dorsal thalamus (except for a thin ventral band close to the alar-basal boundary), the epithalamus, the epiphysis in prosomere p2, the supraoptic-paraventricular area, the eminentia thalami (p4 prosomere), the retrochiasmatic area and the tuberal hypothalamus at 13.5 dpc. In the mesencephalon, expressed in the tectum, the walls of the hindbrain, in nuclei of the ventral midbrain and hindbrain at 13.5 dpc. In the spinal cord, expressed as a gradient in the dorsal part of the neuroepithelium at 13.5 dpc. In the neocortical neuroepithelium, expressed in the archicortex (in the dentate gyrus, CA3 and CA4), the diencephalon, the midbrain and hindbrain at 14.5 and 16.5 dpc.|||Interacts with LDB1 and LDB2.|||Involved in gonadal development.|||Nucleus http://togogenome.org/gene/10090:Tmprss2 ^@ http://purl.uniprot.org/uniprot/Q9JIQ8 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9) and is involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity.|||Belongs to the peptidase S1 family.|||Cell membrane|||Knockout mice show normal growth and reach normal adulthood without having abnormalities in organ histology and alteration in protein levels of prostatic secretions (PubMed:16428450). Abrogation of viral spread and protection of mice from severe pathology and death are observed after infection with influenza A virus strains H1N1 and H7N9.|||Larynx, trachea and bronchi, lung, prostate and kidney.|||Plasma membrane-anchored serine protease that cleaves at arginine residues (By similarity). Participates in proteolytic cascades of relevance for the normal physiologic function of the prostate. Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption (By similarity). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (PubMed:25734995).|||Proteolytically processed; by an autocatalytic mechanism.|||Secreted|||The catalytically active form interacts with ACE2. http://togogenome.org/gene/10090:Puf60 ^@ http://purl.uniprot.org/uniprot/Q3UEB3 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RRM half pint family.|||DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with RO60. Binds to poly(U) RNA (By similarity).|||Homodimer (By similarity). Associates with the spliceosome (By similarity). Found in a complex with RO60 and Y5 RNA (By similarity). Found in a complex with FUBP1 and far upstream element (FUSE) DNA segment (By similarity). Interacts directly with ERCC3. Interacts with CDK7 and GTF2H1 (By similarity). Interacts with SRSF11/P54 (By similarity).|||Nucleus|||The third RNA recognition motif, called PUMP domain, is atypical and may rather mediate homodimerization and/or protein-protein interactions. http://togogenome.org/gene/10090:Or13p3 ^@ http://purl.uniprot.org/uniprot/Q7TQV4 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Musk ^@ http://purl.uniprot.org/uniprot/E9PVV8|||http://purl.uniprot.org/uniprot/Q1XD56|||http://purl.uniprot.org/uniprot/Q32S49|||http://purl.uniprot.org/uniprot/Q32S50|||http://purl.uniprot.org/uniprot/Q32SD3|||http://purl.uniprot.org/uniprot/Q497X0|||http://purl.uniprot.org/uniprot/Q61006 ^@ Activity Regulation|||Caution|||Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily. Tyr protein kinase family.|||Expressed preferentially in skeletal muscle.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Mice die perinatally being unable to take a breath and to respond to tail or leg pinch. Despite the presence of apparently normal skeletal muscle, the absence of differentiated nerve terminals is sufficient to account for this phenotype. Every aspect of NMJ formation examined is absent in these mice. Branches of the main intramuscular nerve do not establish normal contacts with the muscle, do not form correctly positioned or specialized nerve terminals, and are apparently not given appropriate signals to stop their wandering aimlessly across the muscle. Furthermore, postsynaptic differentiation is absent, muscle-derived proteins normally localized to the synaptic basal lamina or the postsynaptic membrane being uniformly distributed in myofibers.|||Monomer. Homodimer (Probable). Interacts with LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK. Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via cytoplasmic part) with DOK7 (via IRS-type PTB domain); requires MUSK phosphorylation. Interacts with DVL1 (via DEP domain); the interaction is direct and mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering. Interacts with PDZRN3; this interaction is enhanced by agrin. Interacts with FNTA; the interaction is direct and mediates AGRIN-induced phosphorylation and activation of FNTA. Interacts with CSNK2B; mediates regulation by CK2. Interacts (via the cytoplasmic domain) with DNAJA3. Interacts with NSF; may regulate MUSK endocytosis and activity. Interacts with CAV3; may regulate MUSK signaling. Interacts with RNF31.|||Neddylated.|||Phosphorylated (PubMed:16818610). Phosphorylation is induced by AGRIN (PubMed:8653787, PubMed:18848351). Autophosphorylated. Autophosphorylation at Tyr-553 is required for interaction with DOK7 which in turn stimulates the phosphorylation and the activation of MUSK (PubMed:16794080, PubMed:20603078).|||Positively regulated by CK2.|||Postsynaptic cell membrane|||Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation.|||Skeletal myogenesis is a major site of expression during normal embryogenesis. In addition, the ganglia of the developing peripheral nervous system and various embryonic epithelia, including those of kidney, lung and gut are also sites of expression.|||Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and lysosomal degradation. http://togogenome.org/gene/10090:Slc7a12 ^@ http://purl.uniprot.org/uniprot/Q8VIE6 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basal cell membrane|||Belongs to the amino acid-polyamine-organocation (APC) superfamily.|||Cytoplasm|||Expressed in kidney and red blood cells (at protein level) (PubMed:11591708). Expressed in kidney along the collecting ducts in the cortex, outer and inner medulla (PubMed:11591708, PubMed:11943479). May be expressed in placenta, lungs, spleen and skeletal muscles (PubMed:11591708).|||Expression in spleen is up-regulated in response to anemia.|||Inactive as a transporter when expressed alone or co-expressed with SLC3A1 or SLC3A2 (PubMed:11943479, PubMed:11591708). Functional as a transporter when fused (via the C-terminus) with SLC3A1 or SLC3A2 (PubMed:11591708).|||Probably forms multimers, perhaps with an unknown protein(s).|||Probably mediates sodium- and chloride-independent uptake of neutral amino acids. http://togogenome.org/gene/10090:Tcp1 ^@ http://purl.uniprot.org/uniprot/P11983 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TCP-1 chaperonin family.|||Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG. Interacts with GBA1 (By similarity). Interacts with DLEC1 (By similarity).|||Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis. The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance. As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. The TRiC complex plays a role in the folding of actin and tubulin.|||centrosome|||cytosol http://togogenome.org/gene/10090:Lrr1 ^@ http://purl.uniprot.org/uniprot/D3YY91 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the probable ECS(LRR1) E3 ubiquitin-protein ligase complex which contains CUL2, RBX1, Elongin BC complex and LRR1. Interacts with CUL2, RBX1, ELOB and ELOC.|||Nucleus|||Substrate recognition subunit of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:33590678). ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (PubMed:33590678). May negatively regulate the 4-1BB-mediated signaling cascades which result in the activation of NK-kappaB and JNK1 (By similarity). http://togogenome.org/gene/10090:Arhgef2 ^@ http://purl.uniprot.org/uniprot/H3BJ40|||http://purl.uniprot.org/uniprot/H3BJ45|||http://purl.uniprot.org/uniprot/Q60875 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (By similarity). Involved in neuronal progenitor cell division and differentiation (PubMed:28453519). Involved in the migration of precerebellar neurons (PubMed:28453519).|||Cytoplasm|||Cytoplasmic vesicle|||Expressed in the neuroepithelium of telencephalon, diencephalon and rhombencephalon at 11 dpc (PubMed:28453519).|||Found in a complex composed at least of ARHGEF2, NOD2 and RIPK2. Interacts with RIPK2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-885. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with RHOA and RAC1. Interacts with NOD1 (By similarity). Interacts (via the N- terminal zinc finger) with CAPN6 (via domain II). Interacts with DYNLT1.|||Golgi apparatus|||Mice show reduced volume of the total brain, the cerebellum and the brainstem. Show complete lack of precerebellar pontin gray and reticulotegmental nuclei. Show impaired precerebellar neuron migration.|||Phosphorylation of Ser-885 by PAK1 induces binding to protein YWHAZ, promoting its relocation to microtubules and the inhibition of its activity. Phosphorylated by AURKA and CDK1 during mitosis, which negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3 increases nucleotide exchange activity. Phosphorylation by PAK4 releases GEF-H1 from the microtubules. Phosphorylated on serine, threonine and tyrosine residues in a RIPK2-dependent manner (By similarity).|||The DH (DBL-homology) domain promotes tyrosine phosphorylation of RIPK2 (By similarity). The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA.|||The PH domain has no affinity for phosphoinositides suggesting that it does not interact directly with membranes.|||The phorbol-ester/DAG-type zinc-finger and the C-terminal coiled-coil domains (606-986) are both important for association with microtubules.|||Ubiquitous, with the exception of liver tissue. Levels are high in hemopoietic tissues (thymus, spleen, bone marrow) as well as in kidney and lung. Expressed in the germinal zones of both the neocortex and the cerebellum and in the pontine gray nuclei (PubMed:28453519).|||Vesicle|||cytoskeleton|||spindle|||tight junction http://togogenome.org/gene/10090:Gcm2 ^@ http://purl.uniprot.org/uniprot/O09102 ^@ Domain|||Function|||Subcellular Location Annotation ^@ Nucleus|||The C-terminal conserved inhibitory domain (CCID) negatively regulates the transcriptional activity of the protein.|||Transcription factor that binds specific sequences on gene promoters and activate their transcription. Through the regulation of gene transcription, may play a role in parathyroid gland development. http://togogenome.org/gene/10090:Smim29 ^@ http://purl.uniprot.org/uniprot/Q8R043 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fndc7 ^@ http://purl.uniprot.org/uniprot/A2AED3 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Vmn1r142 ^@ http://purl.uniprot.org/uniprot/K7N6U0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Stx5a ^@ http://purl.uniprot.org/uniprot/Q8K1E0 ^@ Caution|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||It is uncertain whether Met-1 or Met-55 is the initiator. However, for the rat ortholog it has been shown that the equivalent alternative isoform is produced by alternative initiation at a conserved initiator methionine at position 55.|||Mediates endoplasmic reticulum to Golgi transport. Together with p115/USO1 and GM130/GOLGA2, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus.|||Part of a ternary complex containing STX5A, NSFL1C and VCP. Part of a unique SNARE complex composed of the Golgi SNAREs GOSR1, GOSR2, YKT6 and VTI1A (PubMed:9705316). Interacts with COG4 (By similarity). Interacts with GM130/GOLGA2 (By similarity). Interacts (via IxM motif) with SEC24C and SEC24D; mediates STX5 packaging into COPII-coated vesicles (By similarity). Interacts with VLDLR; this interaction mediates VLDLR translocation from the endoplasmic reticulum to the plasma membrane (By similarity).|||Produced by alternative initiation at Met-55 of isoform 1. http://togogenome.org/gene/10090:Srebf1 ^@ http://purl.uniprot.org/uniprot/Q9WTN3 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activation by cleavage is down-regulated upon activation of SIRT3-dependent PRKAA1/AMPK-alpha signaling cascade which leads to inhibition of ATP-consuming lipogenesis to restore cellular energy balance.|||Belongs to the SREBP family.|||COPII-coated vesicle membrane|||Efficient DNA binding of the soluble transcription factor fragment requires dimerization with another bHLH protein (By similarity). Interacts with CEBPA, the interaction produces a transcriptional synergy (PubMed:17290224). Interacts with LMNA (PubMed:11929849).|||Endoplasmic reticulum membrane|||Expressed in a circadian manner in the liver with a peak at ZT16 (PubMed:19786558).|||Expressed only in select tissues, such as intestinal epithelial, heart, macrophage and bone marrow dendritic cells (PubMed:9062340, PubMed:21531336). Also found in kidney, thymus, testis, muscle, jejunum, and ileum (PubMed:9062340).|||Forms a tight complex with SCAP, the SCAP-SREBP complex, in the endoplasmic reticulum membrane.|||Golgi apparatus membrane|||Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (PubMed:12855691, PubMed:21531336). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:8833906). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (PubMed:9062341, PubMed:12855691). Required for innate immune response in macrophages by regulating lipid metabolism (PubMed:21531336).|||Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:19244231, PubMed:17290224, PubMed:9329978, PubMed:9784493, PubMed:21459323). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') (By similarity). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (By similarity). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:19244231, PubMed:17290224, PubMed:9329978, PubMed:9784493, PubMed:21459323).|||Mice lacking isoform SREBP-1A are resistant to pro-inflammatory toxic shock (PubMed:21531336). Macrophages challenged with bacterial lipopolysaccharide fail to activate lipogenesis as well as hallmarks of inflammasome functions, activation of caspase-1 and secretion of IL1B (PubMed:21531336).|||Mice lacking isoform SREBP-1C show a lack of up-regulation of several lipogenic enzymes in response to high insulin or LXR activation.|||Mice show high embryonic lethality around day 11 dpc (PubMed:9329978). Surviving mice show a 2-3-fold increase in processed Srebpf2 protein in liver nuclei, 3-fold increase in cholesterol synthesis and 50% increase in cholesterol content of the liver (PubMed:9329978).|||Nucleus|||Phosphorylated by AMPK, leading to suppress protein processing and nuclear translocation, and repress target gene expression. Phosphorylation at Ser-389 by SIK1 represses activity possibly by inhibiting DNA-binding.|||Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:11782483, PubMed:12855691, PubMed:19244231). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:11782483, PubMed:12855691, PubMed:16100574, PubMed:19244231).|||Predominant isoform expressed in most tissues (PubMed:21531336). Predominates in liver, adrenal gland, brain and adipose tissue (PubMed:9062340). Also found in kidney, thymus, testis, muscle, jejunum, and ileum (PubMed:9062340).|||Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (PubMed:12855691, PubMed:21531336). Primarily controls expression of lipogenic gene (PubMed:8833906, PubMed:9062341). Strongly activates global lipid synthesis in rapidly growing cells (PubMed:8833906, PubMed:9062341).|||Processed in the Golgi apparatus, releasing the protein from the membrane. At low cholesterol the SCAP-SREBP complex is recruited into COPII vesicles for export from the endoplasmic reticulum. In the Golgi, complex SREBPs are cleaved sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases (By similarity). The first cleavage by site-1 protease occurs within the luminal loop, the second cleavage by site-2 protease occurs within the first transmembrane domain, releasing the transcription factor from the Golgi membrane (By similarity).|||The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.|||Ubiquitinated; the nuclear form has a rapid turnover and is rapidly ubiquitinated and degraded by the proteasome in the nucleus.|||Up-regulated by endocannabinoid anandamide/AEA. http://togogenome.org/gene/10090:Stat5b ^@ http://purl.uniprot.org/uniprot/P42232 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the transcription factor STAT family.|||Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation.|||Cytoplasm|||Detected both in virgin mouse and after mammary gland involution. The level of STAT5A increases constantly during pregnancy, but decreases during lactation.|||In the virgin, found in most tissues. Particularly abundant in muscle tissue of virgin and lactating females, and of males.|||Nucleus|||Tyrosine phosphorylated in response to signaling via activated KIT, resulting in translocation to the nucleus. Tyrosine phosphorylated in response to signaling via activated FLT3; wild-type FLT3 results in much weaker phosphorylation than constitutively activated mutant FLT3. Alternatively, can be phosphorylated by JAK2 (By similarity). Phosphorylation at Tyr-699 by PTK6 or HCK leads to an increase of its transcriptional activity (By similarity).|||Upon activation, forms a homodimer or a heterodimer with a related family member. Binds NR3C1 (PubMed:9528750). Interacts with NCOA1 (By similarity). Interacts with SOCS7 (By similarity). Interacts (via SH2 domain) with INSR (PubMed:9428692). Interacts with CPEB3; this inhibits STAT5B-mediated transcriptional activation (PubMed:20639532). http://togogenome.org/gene/10090:Ifna2 ^@ http://purl.uniprot.org/uniprot/B1AYH7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Ntmt1 ^@ http://purl.uniprot.org/uniprot/Q8R2U4 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methyltransferase superfamily. NTM1 family.|||Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of the exposed alpha-amino group of the Ala, Gly or Ser residue in the [Ala/Gly/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif (PubMed:20668449). Some of the substrates may be primed by NTMT2-mediated monomethylation. Catalyzes the trimethylation of the N-terminal Gly in CENPA (after removal of Met-1) (By similarity). Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1 (PubMed:20668449).|||Nucleus http://togogenome.org/gene/10090:Gstm5 ^@ http://purl.uniprot.org/uniprot/P48774 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the GST superfamily. Mu family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.|||Cytoplasm|||Homodimer (By similarity). Interacts with PFKM isoform 2 and isoform 3 (via N-terminal testis-specific region) (PubMed:19889946). http://togogenome.org/gene/10090:Clasrp ^@ http://purl.uniprot.org/uniprot/Q8CFC7 ^@ Caution|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the splicing factor SR family.|||Highly expressed in brain. Expressed at intermediate level in lung and liver. In brain, it is expressed in the hippocampus, cerebellum and olfactory bulb.|||It is uncertain whether Met-1 or Met-16 is the initiator.|||Nucleus|||Phosphorylated in vitro by CLK4.|||Probably functions as an alternative splicing regulator. May regulate the mRNA splicing of genes such as CLK1. May act by regulating members of the CLK kinase family.|||Probably interacts with CLK4.|||nucleoplasm http://togogenome.org/gene/10090:Dpagt1 ^@ http://purl.uniprot.org/uniprot/P42867|||http://purl.uniprot.org/uniprot/Q9CPT1 ^@ Activity Regulation|||Developmental Stage|||Disruption Phenotype|||Function|||RNA Editing|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Activated by mannosylphosphoryldolichol and phospholipids such as phosphatidylglycerol and phosphatidylcholine. Inhibited by natural nucleoside antibiotic tunicamycin, which acts as a structural analog and competitor of UDP-GlcNAc.|||Belongs to the glycosyltransferase 4 family.|||Catalyzes the initial step of dolichol-linked oligosaccharide biosynthesis in N-linked protein glycosylation pathway: transfers GlcNAc-1-P from UDP-GlcNAc onto the carrier lipid dolichyl phosphate (P-dolichol), yielding GlcNAc-P-P-dolichol.|||Endoplasmic reticulum membrane|||Highest activity is during the mid-phase of lactation.|||Homodimer.|||Membrane|||Mice die 4 to 5 days post-fertilization, just after implantation, suggesting that protein function and N-glycosylation are essential in early embryogenesis.|||Partially edited. http://togogenome.org/gene/10090:Dhrs4 ^@ http://purl.uniprot.org/uniprot/Q99LB2 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the short-chain dehydrogenases/reductases (SDR) family.|||Homotetramer.|||NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quinones. Reduces all-trans-retinal and 9-cis retinal. Reduces 3-ketosteroids and benzil into 3alpha-hydroxysteroids and S-benzoin, respectively, in contrast to the stereoselectivity of primates DHRS4s which produce 3beta-hydroxysteroids and R-benzoin. In the reverse reaction, catalyzes the NADP-dependent oxidation of 3alpha-hydroxysteroids and alcohol, but with much lower efficiency. Involved in the metabolism of 3alpha-hydroxysteroids, retinoid, isatin and xenobiotic carbonyl compounds.|||Peroxisome|||Primate DHRS4s display different stereoselectivity and catalytic efficiency in the oxidoreduction of some substrates as compared to other mammal DHRS4s due to a difference in conserved amino acid residues.|||The C-terminus peroxisomal targeting signal tripeptide is important for peroxisomal import. Once in the peroxisome, it is involved in intersubunit interactions.|||Three specific residues, Phe-177, Leu-180 and Asn-196 are conserved between non-primate mammals whereas the respective residues are serine, phenylalanine and threonine in primates. The two residues at positions 177 and 180 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil. The presence of an asparagine at position 196 is important for the maintenance of the quaternary structure resulting in stability at cold temperature and improved catalytic activity toward retinal. http://togogenome.org/gene/10090:Fam91a1 ^@ http://purl.uniprot.org/uniprot/B6YY24|||http://purl.uniprot.org/uniprot/Q3UVG3 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1.|||Belongs to the FAM91 family.|||Component of the complex WDR11 composed of C17orf75, FAM91A1 and WDR11; FAM91A1 and WDR11 are required for proper location of the complex (By similarity). Interacts with golgins GOLGA1 and GOLGA4 and with TBC1D23; interaction with golgins may be mediated by TBC1D23 and interaction with TBC1D23 recruits TBC1D23 to AP-1-derived vesicles (PubMed:29084197).|||Cytoplasmic vesicle|||trans-Golgi network http://togogenome.org/gene/10090:Kctd8 ^@ http://purl.uniprot.org/uniprot/Q50H33 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Auxiliary subunit of GABA-B receptors that determine the pharmacology and kinetics of the receptor response. Increases agonist potency and markedly alter the G-protein signaling of the receptors by accelerating onset and promoting desensitization.|||Interacts as a tetramer with GABRB1 and GABRB2.|||Postsynaptic cell membrane|||Presynaptic cell membrane http://togogenome.org/gene/10090:Brca2 ^@ http://purl.uniprot.org/uniprot/P97929 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ In the mammary gland, expression increases dramatically during pregnancy.|||Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability, independently of its known role in homologous recombination (By similarity).|||Monomer and dimer. Interacts with RAD51; regulates RAD51 recruitment and function at sites of DNA repair. Interacts with SEM1, WDR16, USP11, DMC1, ROCK2 and NPM1. Interacts with both nonubiquitinated and monoubiquitinated FANCD2; this complex also includes XRCC3 and phosphorylated FANCG. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (By similarity). Within the complex, interacts with ERCC5/XPG and PALB2 (By similarity). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with BRCA1 only in the presence of PALB2 which serves as the bridging protein. Interacts with POLH; the interaction is direct. Interacts with the TREX-2 complex subunits PCID2 and SEM1 (By similarity). Interacts with HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the formation of a ternary complex (PubMed:32345962, PubMed:32460033, PubMed:31242413, PubMed:30760716, PubMed:32845237). The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (PubMed:32345962, PubMed:30760716).|||Nucleus|||Phosphorylated by ATM upon irradiation-induced DNA damage. Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when recombination is active, but increases as cells progress towards mitosis; this phosphorylation prevents homologous recombination-dependent repair during S phase and G2 by inhibiting RAD51 binding.|||Ubiquitinated in the absence of DNA damage; this does not lead to proteasomal degradation. In contrast, ubiquitination in response to DNA damage leads to proteasomal degradation.|||Widely expressed. Highest expression in cerebellum, testis, ileum, appendix, epididymis, ovary and mammary gland. No expression in lung.|||centrosome http://togogenome.org/gene/10090:Med25 ^@ http://purl.uniprot.org/uniprot/A0A140LHG7|||http://purl.uniprot.org/uniprot/Q8VCB2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Mediator complex subunit 25 family.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.|||Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for RARA/RXRA-mediated transcription (By similarity).|||Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with CREBBP. Interacts with ESR1, GR and THRB in a ligand-dependent fashion. Binds the Herpes simplex virus activator VP16 (By similarity). Interacts with RARA and RXRA in a ligand-dependent fashion.|||Component of the Mediator complex.|||Nucleus http://togogenome.org/gene/10090:Pcyox1l ^@ http://purl.uniprot.org/uniprot/Q8C7K6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the prenylcysteine oxidase family.|||Probable oxidoreductase.|||Secreted http://togogenome.org/gene/10090:Krt86 ^@ http://purl.uniprot.org/uniprot/B2RTB6|||http://purl.uniprot.org/uniprot/P97861 ^@ Miscellaneous|||Similarity|||Subunit ^@ Belongs to the intermediate filament family.|||Heterotetramer of two type I and two type II keratins.|||There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic). http://togogenome.org/gene/10090:Mettl1 ^@ http://purl.uniprot.org/uniprot/Q9Z120 ^@ Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class I-like SAM-binding methyltransferase superfamily. TrmB family.|||Catalytic component of METTL1-WDR4 methyltransferase complex that mediates the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (By similarity). Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (By similarity). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (By similarity). Also acts as a methyltransferase for a subset of internal N(7)-methylguanine in mRNAs (PubMed:29983320). Internal N(7)-methylguanine methylation of mRNAs in response to stress promotes their relocalization to stress granules, thereby suppressing their translation (PubMed:29983320). Also methylates a specific subset of miRNAs, such as let-7 (By similarity). N(7)-methylguanine methylation of let-7 miRNA promotes let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA) (By similarity). Acts as a regulator of embryonic stem cell self-renewal and differentiation (PubMed:29983320).|||Catalytic component of the METTL1-WDR4 complex, composed of METTL1 and WDR4.|||Conditional knockout in the liver impairs the formation of N(7)-methylguanine at position 46 (m7G46) in tRNAs and inhibits tumor development in an intrahepatic cholangiocarcinoma xenograph mouse model.|||In the context of cancer, overexpression of the METTL1-WDR4 methyltransferase complex promotes cancer progression by driving oncogenic transformation (PubMed:34352206). Drives oncogenesis by mediating the formation of N(7)-methylguanine at position 46 (m7G46) in some tRNAs, in particular Arg-TCT-4-1 (TRR-TCT4-1), leading to increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon (PubMed:34352206).|||Nucleus|||Phosphorylation at Ser-21 by PKB/AKT1 inactivates its methyltransferase activity via a steric interference mechanism in the active site that locally disrupts the catalytic center (By similarity). Phosphorylation at Ser-21 does not affect the interaction with WDR4 (By similarity).|||Upon tRNA-binding, the alphaC region transforms into a helix, which together with the alpha6 helix secures both ends of the tRNA variable loop (By similarity). The N-terminal disordered region is part of the catalytic pocket and essential for methyltransferase activity: upon S-adenosyl-L-methionine- and tRNA-binding, the N-terminal disordered region becomes ordered, sandwiched between the bound cofactor and the tRNA, and the WDR4 C-terminus attaches to the METTL1 N-terminus to stabilize the bound tRNA together (By similarity). Together with WDR4, which also binds tRNAs, tRNAs undergo bending to facilitate G46 flipping into the catalytic pocket to be modified (By similarity). http://togogenome.org/gene/10090:Bsnd ^@ http://purl.uniprot.org/uniprot/Q8VIM4 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Basolateral cell membrane|||Expression is evident in inner and outer stripes of the outer medulla of the kidney, most probably representing thin limbs of Henle's loop together with some collecting duct coursing through the outer stripe. In situ hybridization in fetal kidney at 18.5 dpc revealed a clear continuity between hybridization signals from the thin limb of Henle's loop and the distal convoluted tubule, suggesting that part of the expression pattern may result from expression in the thick ascending limb of Henle's loop. In addition, strong signals are present in a subset of cortical tubules, representing distal convoluted tubules or cortical collecting duct. Strong expression is also observed in the inner medulla of the kidney. This expression does not extend all the way to the tip of the papilla. Thus this signal most probably represents cells of the thin ascending limbs. In the inner ear, strong and exclusive expression is detected in marginal cells of the stria vascularis. In addition to cochlear signal, expression is observed in dark cells localized at the base of the crista ampullaris of the vestibular organ.|||Functions as a beta-subunit for CLCNKA and CLCNKB chloride channels. In the kidney CLCNK/BSND heteromers mediate chloride reabsorption by facilitating its basolateral efflux. In the stria, CLCNK/BSND channels drive potassium secretion by recycling chloride for the basolateral SLC12A2 cotransporter.|||Interacts with CLCNK channels. Forms probably heteromers with CLCNKA in the thin ascending limb of Henle and with CLCNKB in the thick ascending limb and more distal segments.|||Palmitoylation is necessary for activation of plasma membrane-inserted CLC-K/barttin channels. http://togogenome.org/gene/10090:Gp1bb ^@ http://purl.uniprot.org/uniprot/P56400 ^@ Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Gp-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to von Willebrand factor, which is already bound to the subendothelium.|||Membrane|||Platelet activation apparently involves disruption of the macromolecular complex of GP-Ib with the platelet glycoprotein IX (GP-IX) and dissociation of GP-Ib from the actin-binding protein.|||Two GP-Ib beta are disulfide-linked to one GP-Ib alpha. GP-IX is complexed with the GP-Ib heterodimer via a non covalent linkage. Interacts with TRAF4 (By similarity). http://togogenome.org/gene/10090:Ctdp1 ^@ http://purl.uniprot.org/uniprot/Q7TSG2 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Homodimer. Interacts with GTF2F1 (By similarity). Interacts with WDR77, SNRPB and SNRNP70 (By similarity).|||Midbody|||Nucleus|||Phosphorylated. In the presence of TFIIF, the phosphorylated form has an increased CTD phosphatase activity. The phosphorylation is required for the physical interaction with GTF2F1 (By similarity).|||Processively dephosphorylates 'Ser-2' and 'Ser-5' of the heptad repeats YSPTSPS in the C-terminal domain of the largest RNA polymerase II subunit. This promotes the activity of RNA polymerase II. Plays a role in the exit from mitosis by dephosphorylating crucial mitotic substrates (USP44, CDC20 and WEE1) that are required for M-phase-promoting factor (MPF)/CDK1 inactivation (By similarity).|||centrosome|||spindle|||spindle pole http://togogenome.org/gene/10090:Gm14743 ^@ http://purl.uniprot.org/uniprot/A2BHD2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the calycin superfamily. Lipocalin family.|||Secreted http://togogenome.org/gene/10090:Slc24a4 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0Z4|||http://purl.uniprot.org/uniprot/Q8CGQ8 ^@ Caution|||Disruption Phenotype|||Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.|||Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+) (PubMed:22057188). Controls the rapid response termination and proper regulation of adaptation in olfactory sensory neurons (OSNs) which subsequently influences how odor information is encoded and perceived (PubMed:22057188). May play a role in calcium transport during amelogenesis (PubMed:23375655).|||Cell membrane|||Cytoplasm|||Expressed in late secretory-stage and maturation-stage ameloblasts, with significantly increased expression during the late stages of amelogenesis (at protein level) (PubMed:22677781, PubMed:24621671, PubMed:26247047). Widely expressed in most regions of the brain, including hippocampus, neocortex, thalamus, striatum and olfactory bulb (PubMed:12379639). Expressed in the olfactory sensory neurons (PubMed:22057188).|||It is uncertain whether Met-1 or Met-18 is the initiator.|||Membrane|||Mice have a reduced ability to locate an odorous source and lower body weights. The olfactory sensory neurons display defects in response termination and adaptation but have unchanged sensitivity (PubMed:22057188). Mice show severe enamel defects (PubMed:23375655).|||Probable cloning artifact. http://togogenome.org/gene/10090:Nup155 ^@ http://purl.uniprot.org/uniprot/Q6ZQ45|||http://purl.uniprot.org/uniprot/Q99P88 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the non-repetitive/WGA-negative nucleoporin family.|||Disulfide-linked to NUP62. The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.|||Essential component of nuclear pore complex. Could be essessential for embryogenesis. Nucleoporins may be involved both in binding and translocating proteins during nucleocytoplasmic transport.|||Homozygous null mice die before embryonic day 8.5.|||Interacts with GLE1 and NUP35/NUP53. Able to form a heterotrimer with GLE1 and NUP42 in vitro (By similarity). Forms a complex with NUP35, NUP93, NUP205 and lamin B (By similarity).|||Nucleus membrane|||Phosphorylated. Phosphorylation and dephosphorylation may be important for the function of NUP155 and may play a role in the reversible disassembly of the nuclear pore complex during mitosis (By similarity).|||nuclear pore complex http://togogenome.org/gene/10090:Hspbp1 ^@ http://purl.uniprot.org/uniprot/Q99P31 ^@ Function|||Subunit ^@ Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of target proteins (By similarity).|||Interacts with the ATP-binding domain of HSPA1A. Detected in a ternary complex containing STUB1, HSPA1A and HSPBP1 (By similarity). Interacts with PGLYRP1; this interaction blocks the cytotoxic activity of the PGLYRP1-HSPA1A complex (By similarity). http://togogenome.org/gene/10090:Marveld1 ^@ http://purl.uniprot.org/uniprot/Q7TQJ1 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Microtubule-associated protein that exhibits cell cycle-dependent localization and can inhibit cell proliferation and migration.|||Nucleus|||cytoskeleton http://togogenome.org/gene/10090:Tmco6 ^@ http://purl.uniprot.org/uniprot/Q8BQX5 ^@ Miscellaneous|||Subcellular Location Annotation ^@ May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Membrane http://togogenome.org/gene/10090:Lrtm2 ^@ http://purl.uniprot.org/uniprot/Q8BGX3 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Bud13 ^@ http://purl.uniprot.org/uniprot/Q8R149 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC26 family.|||Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity).|||Nucleus|||Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed of at least 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Component of the minor spliceosome, which splices U12-type introns (By similarity). http://togogenome.org/gene/10090:Mup3 ^@ http://purl.uniprot.org/uniprot/P04939|||http://purl.uniprot.org/uniprot/Q3KQQ2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Abundant in the urine of adult male mice but absent from that of females.|||Belongs to the calycin superfamily. Lipocalin family.|||Binds pheromones that are released from drying urine of males. These pheromones affect the sexual behavior of females.|||Glycosylated.|||Secreted http://togogenome.org/gene/10090:Ppp2r3c ^@ http://purl.uniprot.org/uniprot/Q9JK24 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Detected from 6 to 12 dpc in whole embryos and from 14 to 18 dpc in the heads of the embryos. Expressed in central nervous system, spine, face, pharynx, limbs and viscera at 11 dpc.|||Expressed in all tissues tested including heart, brain, spleen, thymus, lung, liver, kidney and testis.|||Interacts with MCM3AP/GANP, PPP5C, and the phosphatase 2A core enzyme composed of the PPP2CA catalytic subunit and the constant regulatory subunit PPP2R1A. Finds in a complex with ABCB1, TFPI2 and PPP2R3C; leading to the dephosphorylation of ABCB1.|||May regulate MCM3AP phosphorylation through phosphatase recruitment (PubMed:12167160). May act as a negative regulator of ABCB1 expression and function through the dephosphorylation of ABCB1 by TFPI2/PPP2R3C complex (By similarity). May play a role in the activation-induced cell death of B-cells (PubMed:16129705, PubMed:16343422).|||Mice display a reduction in the number of mature B-cells and an impaired B-cell proliferation upon B-Cell receptor cross-linking probably due to a loss of inhibition of BCR-induced apoptosis. PPP2R3C overexpression protects B-cells from activation-induced cell death.|||Nucleus|||Up-regulated upon B-cell receptor cross-linking. http://togogenome.org/gene/10090:Hhla1 ^@ http://purl.uniprot.org/uniprot/Q3TYV2 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Get1 ^@ http://purl.uniprot.org/uniprot/Q8K0D7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the WRB/GET1 family.|||Component of the Golgi to ER traffic (GET) complex, which is composed of GET1, CAMLG/GET2 and GET3. Within the complex, GET1 and CAMLG form a heterotetramer which is stabilized by phosphatidylinositol binding and which binds to the GET3 homodimer. Interacts with CAMLG/GET2 (via C-terminus). GET3 shows a higher affinity for CAMLG than for GET1.|||Endoplasmic reticulum membrane|||Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Together with CAMLG/GET2, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. Required to ensure correct topology and ER insertion of CAMLG. http://togogenome.org/gene/10090:Rpl10 ^@ http://purl.uniprot.org/uniprot/A2AM97|||http://purl.uniprot.org/uniprot/Q6ZWV3 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uL16 family.|||Citrullinated by PADI4.|||Component of the large ribosomal subunit (PubMed:36517592). Mature ribosomes consist of a small (40S) and a large (60S) subunit (PubMed:36517592). The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S) (PubMed:36517592). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S) (PubMed:36517592).|||Component of the large ribosomal subunit. Plays a role in the formation of actively translating ribosomes (PubMed:36517592). May play a role in the embryonic brain development (By similarity).|||Cytoplasm|||Ufmylated by UFL1. http://togogenome.org/gene/10090:Milr1 ^@ http://purl.uniprot.org/uniprot/Q3TB92 ^@ Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Enhanced IgE-mediated, mast cell-dependent passive systemic anaphylaxis. No effect on differentiation of hematopoietic cells, including mast cells.|||Expressed in myeloid cells (dendritic cells, macrophages and neutrophils but not in T-cells, B-cells or natural killer cells) and mast cells (at protein level).|||Immunoglobulin-like receptor which plays an inhibitory role in degranulation of mast cells. Negatively regulates IgE-mediated mast cell activation and suppresses the type I immediate hypersensitivity reaction.|||Monomer (Probable). Interacts (tyrosine-phosphorylated) with PTPN6, PTPN11 and INPP5D.|||N-glycosylated.|||Secreted http://togogenome.org/gene/10090:St3gal2 ^@ http://purl.uniprot.org/uniprot/Q11204 ^@ Disruption Phenotype|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A beta-galactoside alpha2-3 sialyltransferase primarily involved in terminal sialylation of ganglio and globo series glycolipids (PubMed:8144500, PubMed:9184827). Catalyzes the transfer of sialic acid (N-acetyl-neuraminic acid; Neu5Ac) from the nucleotide sugar donor CMP-Neu5Ac onto acceptor Galbeta-(1->3)-GalNAc-terminated glycoconjugates through an alpha2-3 linkage. Sialylates GM1/GM1a, GA1/asialo-GM1 and GD1b gangliosides to form GD1a, GM1b and GT1b, respectively (PubMed:8144500, PubMed:9184827). Together with ST3GAL3, primarily responsible for biosynthesis of brain GD1a and GT1b that function as ligands for myelin-associated glycoprotein MAG on axons, regulating MAG expression and axonal myelin stability and regeneration (PubMed:22735313). Via GT1b regulates TLR2 signaling in spinal cord microglia in response to nerve injury (PubMed:32030804). Responsible for the sialylation of the pluripotent stem cell- and cancer stem cell-associated antigen SSEA3, forming SSEA4 (By similarity). Sialylates with low efficiency asialofetuin, presumably onto O-glycosidically linked Galbeta-(1->3)-GalNAc-O-Ser (PubMed:8144500).|||Belongs to the glycosyltransferase 29 family.|||Golgi stack membrane|||Homodimer; disulfide-linked. Homodimer formation occurs in the endoplasmic reticulum.|||N-glycosylated; necessary for proper exit from endoplasmic reticulum and trafficking to the Golgi apparatus.|||No visible phenotype under physiological conditions; due to the redundancy with ST3GAL3. Simultaneous knockdown of ST3GAL2 and ST3GAL3 results in markedly fewer offspring and impaired nervous system function at weaning (PubMed:22735313). Knockout mice show reduced nerve injury-induced neuropathic pain in response to noxious stimuli (hyperalgesia) and to normally innocuous stimuli (allodynia) (PubMed:32030804).|||Secreted|||Strongly expressed in brain and liver and to a lesser extent in heart and kidney. Scarcely detectable in lung, pancreas, spleen and submaxillary gland (PubMed:8144500). Expressed in L5 dorsal root ganglion (DRG) neurons (at protein level) (PubMed:32030804).|||The soluble form derives from the membrane form by proteolytic processing.|||Up-regulated in DRG neurons in response to nerve injury. http://togogenome.org/gene/10090:Itgb3 ^@ http://purl.uniprot.org/uniprot/O54890 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Animals are viable and fertile.|||Belongs to the integrin beta chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit (By similarity). Beta-3 (ITGB3) associates with either alpha-IIB (ITGA2B) or alpha-V (ITGAV). Interacts with FLNB and COMP (By similarity). Interacts with PDIA6 following platelet stimulation (By similarity). Interacts with SYK; upon activation by ITGB3 promotes platelet adhesion (By similarity). Interacts with MYO10 (By similarity). Interacts with DAB2 (PubMed:12606711). Interacts with FERMT2 (PubMed:18483218). Integrin ITGAV:ITGB3 interacts with FBLN5 (via N-terminus) (PubMed:11805835). Interacts with EMP2; regulates the levels of the heterodimer ITGA5:ITGB3 integrin expression on the plasma membrane (By similarity). ITGAV:ITGB3 interacts with CCN3 (By similarity). ITGAV:ITGB3 interacts with AGRA2 (By similarity). ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1. ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3. ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1. ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors (By similarity). ITGAV:ITGB3 binds to IL1B (By similarity). ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R (By similarity). ITGAV:ITGB3 interacts with IGF2 (By similarity). ITGAV:ITGB3 interacts with FBN1 (By similarity). ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain) (By similarity). Interacts (via the allosteric site (site 2)) with CXCL12 in a CXCR4-independent manner (By similarity). Interacts with MXRA8/DICAM; the interaction inhibits ITGAV:ITGB3 heterodimer formation (PubMed:22492581). ITGAV:ITGB3 interacts with PTN. Forms a complex with PTPRZ1 and PTN that stimulates endothelial cell migration through ITGB3 Tyr-772 phosphorylation (By similarity). ITGAV:ITGB3 interacts with SLC6A4. Interacts with SLC6A4 (via C-terminus); this interaction regulates SLC6A4 trafficking (PubMed:29038237) (By similarity). ITGA2B:ITGB3 interacts with PPIA/CYPA; the interaction is ROS and PPIase activity-dependent and is increased in the presence of thrombin (PubMed:24429998). Interacts with tensin TNS3; TNS3 also interacts with PEAK1, thus acting as an adapter molecule to bridge the association of PEAK1 with ITGB3 (PubMed:35687021).|||Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIB/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIB/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIB/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIB/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surfaces. Fibrinogen binding enhances SELP expression in activated platelets (PubMed:19332769). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (By similarity). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (By similarity). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (By similarity). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (By similarity). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (By similarity). ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (By similarity). ITGAV:ITGB3 binds to the Lilrb4a/Gp49b receptor and enhances the Lilrb4a-mediated inhibition of mast cell activation (PubMed:11323698). ITGAV:ITGB3 also suppresses marginal zone B cell antibody production through its interaction with Lilrb4a (PubMed:24935931). In brain, plays a role in synaptic transmission and plasticity (PubMed:29038237, PubMed:18549786). Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin (PubMed:29038237). Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition (PubMed:18549786). ITGAV:ITGB3 act as a receptor for CD40LG (By similarity).|||Phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation. Probably involved in outside-in signaling.|||Postsynaptic cell membrane|||Synapse|||The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site.|||focal adhesion|||lamellipodium membrane http://togogenome.org/gene/10090:Mapk10 ^@ http://purl.uniprot.org/uniprot/A0A5F8MP75|||http://purl.uniprot.org/uniprot/Q3TQZ7|||http://purl.uniprot.org/uniprot/Q61831|||http://purl.uniprot.org/uniprot/Q78GB8|||http://purl.uniprot.org/uniprot/Q80W80|||http://purl.uniprot.org/uniprot/Q80W81|||http://purl.uniprot.org/uniprot/Q80W82|||http://purl.uniprot.org/uniprot/Q8C9D4 ^@ Activity Regulation|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax for the enzyme. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1 (By similarity). Inhibited by HDAC9.|||Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.|||Brain (at protein level). Expressed specifically in neurons of the hippocampus, cortex, cerebellum, brainstem, and spinal cord. Seems to be also found in testis, and very weakly in the heart.|||Cytoplasm|||Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro (By similarity).|||Expression begins in day 11.5 dpc embryos, and is localized in both the rostral spinal cord and rhombencephalon. In 12.5-13 dpc embryos, it is found throughout the telencephalon. By day 17.5, JNK3 is also expressed in neurons of dorsal root and sensory ganglia and at lower levels in neurons of the myenteric plexus and the developing heart.|||Interacts with MAPK8IP1/JIP-1, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP4 (By similarity). Interacts with HDAC9 and MAPKBP1 (PubMed:10471813, PubMed:16611996). Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 (By similarity). Interacts with SARM1 (PubMed:17724133). Interacts with JUND; interaction is inhibited in the presence of MEN1 (By similarity).|||Membrane|||Mitochondrion|||Nucleus|||Palmitoylation regulates subcellular location and axonal development.|||Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.|||Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (By similarity).|||The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. http://togogenome.org/gene/10090:Tmem41a ^@ http://purl.uniprot.org/uniprot/Q9CUY8|||http://purl.uniprot.org/uniprot/Q9D8U2 ^@ Domain|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMEM41 family.|||Membrane|||The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain. http://togogenome.org/gene/10090:Fgb ^@ http://purl.uniprot.org/uniprot/Q3TGR2|||http://purl.uniprot.org/uniprot/Q8K0E8 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure (By similarity).|||Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways.|||Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot.|||Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain (By similarity).|||Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain.|||Secreted http://togogenome.org/gene/10090:Gpr162 ^@ http://purl.uniprot.org/uniprot/Q3UN16 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Orphan receptor. http://togogenome.org/gene/10090:Trak2 ^@ http://purl.uniprot.org/uniprot/G3UYW9|||http://purl.uniprot.org/uniprot/Q6P9N8|||http://purl.uniprot.org/uniprot/Q8BZ57 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the milton family.|||Early endosome|||Mitochondrion http://togogenome.org/gene/10090:Xlr5c ^@ http://purl.uniprot.org/uniprot/A2AIE6|||http://purl.uniprot.org/uniprot/Q9JJR2 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the XLR/SYCP3 family.|||Chromosome|||Detected in testis from 1 day postpartum (dpp) onwards (at protein level). Expression increases through to 28 dpp and remains high thereafter (at protein level). Highly expressed in spermatocytes at leptotene and pachytene stages of meiosis.|||Expressed in testis (at protein level). Also expressed in ovary. Not detected in other tissues tested.|||Nucleus http://togogenome.org/gene/10090:Or7g35 ^@ http://purl.uniprot.org/uniprot/Q7TRF8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cenpu ^@ http://purl.uniprot.org/uniprot/Q8C4M7 ^@ Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CENP-U/AME1 family.|||Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression (By similarity).|||Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. Interacts with MLF1 (By similarity).|||Cytoplasm|||Expressed at different stages of development between 7 dpc and 17 dpc, and highest expression seen at 11 dpc. Detected in the liver at 13.5 dpc and strongly expressed in the cephalic mesenchyme and roof of the hindbrain, lining of the pericardial cavity and atrial chamber of the heart and lumen of the stomach in 11.5-day embryos.|||Nucleus|||Phosphorylated by PLK1 at Thr-74, creating a self-tethering site that specifically interacts with the polo-box domain of PLK1.|||Testis, spleen, heart, kidney, liver, lung, brain and CFU-E erythroid precursor cells.|||kinetochore http://togogenome.org/gene/10090:Tgm3 ^@ http://purl.uniprot.org/uniprot/Q08189 ^@ Cofactor|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by proteolytic processing. In vitro activation is commonly achieved by cleavage with dispase, a neutral bacterial protease. Physiological activation may be catalyzed by CTSL and, to a lesser extent, by CTSS (By similarity).|||Belongs to the transglutaminase superfamily. Transglutaminase family.|||Binds 3 Ca(2+) cations per subunit. Binds 1 Ca(2+) as a zymogen, and binds 2 more Ca(2+) cations, or other divalent metal cations, after proteolytic processing.|||Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath.|||Consists of two polypeptide chains, which are synthesized as a precursor form of a single polypeptide.|||Cytoplasm|||Expressed in skin and stomach and, at lower levels, in testis, kidney and spleen (at protein level). On the basis of its catalytic activity, detected in the epidermis, around the granular and spinous layers but not in the outermost cornified layers. In hair follicles, mainly located in the medulla and the hair cortex.|||Expression starts at 11.5 dpc in the early two-layered epidermis. From 12.5 dpc, mainly expressed in the periderm cells and weakly in the epidermal basal cells. After epidermis keratinization, at 15.5 to 17.5 dpc, detected in the granular, cornified layers and in the hair follicle. Also expressed in heart, lung, bone, muscle, testis and blood vessels at 12.5, 13.5, 14.5 and 16.5 dpc, respectively. http://togogenome.org/gene/10090:Myh15 ^@ http://purl.uniprot.org/uniprot/E9Q264 ^@ Similarity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family. http://togogenome.org/gene/10090:Pnlip ^@ http://purl.uniprot.org/uniprot/Q6P8U6 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Forms a 1:1 stoichiometric complex with (pro)colipase/CLPS.|||Inhibited by bile salts, is reactivated by (pro)colipase/CLPS.|||Pancreas.|||Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows considerably higher activity against insoluble emulsified substrates than against soluble ones.|||Secreted http://togogenome.org/gene/10090:Skint10 ^@ http://purl.uniprot.org/uniprot/A7TZG1 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin and thymus.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Defb29 ^@ http://purl.uniprot.org/uniprot/A3KGR0|||http://purl.uniprot.org/uniprot/Q8BGW9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||Has antibacterial activity.|||Highly expressed in the cauda epididymis.|||Secreted http://togogenome.org/gene/10090:Sparcl1 ^@ http://purl.uniprot.org/uniprot/P70663|||http://purl.uniprot.org/uniprot/Q3TYD5|||http://purl.uniprot.org/uniprot/Q3UYK7 ^@ Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SPARC family.|||Highest expression in brain. Moderate levels in heart, adrenal gland, epididymis and lung. Low levels in kidney, eye, liver, spleen, submandibular gland and testis.|||extracellular matrix http://togogenome.org/gene/10090:Incenp ^@ http://purl.uniprot.org/uniprot/Q9WU62 ^@ Caution|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the INCENP family.|||Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex binds directly to AURKB or AURKC via the IN box, and forms a triple-helix bundle-based subcomplex with BIRC5 and CDCA8 via its N-terminus. The reported homodimerization is questioned as the SAH domain is shown to be monomeric. Interacts with H2AZ1. Interacts with CBX1 and CBX3. Interacts with tubulin beta chain. Interacts with EVI5. Interacts with CBX5; POGZ and INCENP compete for interaction with CBX5. Interacts with POGZ. Interacts with JTB.|||Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules. The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC. Controls the kinetochore localization of BUB1.|||Major isoform in thymic lymphoma 3SB cells. Fourfold more abundant than isoform 2.|||Midbody|||Minor isoform in thymic lymphoma 3SB cells.|||Nucleus|||Originally predicted to contain a coiled coil domain but shown to contain a stable SAH domain instead.|||Phosphorylation by AURKB at its C-terminal part is important for AURKB activation by INCENP.|||The IN box mediates interaction with AURKB and AURKC.|||The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric.|||centromere|||kinetochore|||spindle http://togogenome.org/gene/10090:Ap3s2 ^@ http://purl.uniprot.org/uniprot/Q6PAL3|||http://purl.uniprot.org/uniprot/Q8BSZ2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (By similarity). AP-3 associates with the BLOC-1 complex. Interacts with AGAP1.|||Belongs to the adaptor complexes small subunit family.|||Cytoplasmic vesicle membrane|||Golgi apparatus|||Membrane|||Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.|||Present in all adult tissues examined. http://togogenome.org/gene/10090:Or2y8 ^@ http://purl.uniprot.org/uniprot/Q7TQT6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ctsq ^@ http://purl.uniprot.org/uniprot/Q91ZF4 ^@ Similarity ^@ Belongs to the peptidase C1 family. http://togogenome.org/gene/10090:Yae1d1 ^@ http://purl.uniprot.org/uniprot/Q9DAY6 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Dzip3 ^@ http://purl.uniprot.org/uniprot/E9QNZ2|||http://purl.uniprot.org/uniprot/Q7TPV2 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Cytoplasm|||E3 Ubiquitin ligase proteins mediate ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Able to specifically bind RNA.|||Probably interacts with DAZL. http://togogenome.org/gene/10090:U2surp ^@ http://purl.uniprot.org/uniprot/Q6NV83 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the splicing factor SR family.|||Interacts with ERBB4.|||Nucleus http://togogenome.org/gene/10090:Ccdc137 ^@ http://purl.uniprot.org/uniprot/Q8R0K4 ^@ Subcellular Location Annotation ^@ Chromosome http://togogenome.org/gene/10090:Avpr1b ^@ http://purl.uniprot.org/uniprot/Q9WU02 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.|||Cell membrane|||Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system. http://togogenome.org/gene/10090:Matn3 ^@ http://purl.uniprot.org/uniprot/O35701 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can form homooligomers (monomers, dimers, trimers and tetramers) and heterooligomers with matrilin-1. Interacts with COMP (By similarity). Component of a complex containing at least CRELD2, MANF, MATN3 and PDIA4 (PubMed:23956175).|||Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.|||Secreted|||Strongly expressed in growing skeletal tissue such as epiphyseal growth plate or in bone undergoing growth and remodeling. In the bone, actively synthesized in osteoblasts and osteocytes. Expressed in cartilage of sternum, femur, vertebrae, trachea, articular and epiphyseal cartilage, cartilage of developing bones and bones.|||The earliest expression could be detected in a 12.5 dpc embryo in the cartilage anlage of the developing bones. At 14.5 dpc the primordial skeleton shows a strong expression. At birth present in the developing occipital bones, bones of the nasal cavity, manubrium and corpus of sternum as well as in the cartilage plates of trachea. At no stage of development detected in extraskeletal tissues. http://togogenome.org/gene/10090:Or4l15 ^@ http://purl.uniprot.org/uniprot/K7N5X7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gm21118 ^@ http://purl.uniprot.org/uniprot/J3QPK8 ^@ Similarity ^@ Belongs to the SPIN/STSY family. http://togogenome.org/gene/10090:Ccdc63 ^@ http://purl.uniprot.org/uniprot/Q8CDV6 ^@ Disruption Phenotype|||Function|||Tissue Specificity ^@ Expressed in testis, brain, thymus and lung (PubMed:26501274).|||Male mice are infertile despite regular copulation. Display shortened sperm tails and malformed sperm heads and motionless spermatozoa (PubMed:26501274). The 9+2 structure of the axoneme seems to be intact (PubMed:26501274). Spermatozoa are able to activate oocytes when used in intracytoplasmic sperm injection (ICSI) and these embryos are able to develop to term (PubMed:26501274).|||Plays a role in spermiogenesis (PubMed:26501274). Involved in the elongation of flagella and the formation of sperm heads (PubMed:26501274). http://togogenome.org/gene/10090:Akap3 ^@ http://purl.uniprot.org/uniprot/O88987 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the AKAP110 family.|||Interacts with ROPN1 and ROPN1L. Interacts with QRICH2 (By similarity).|||May function as a regulator of both motility- and head-associated functions such as capacitation and the acrosome reaction.|||Phosphorylated on tyrosine.|||RII-binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.|||acrosome http://togogenome.org/gene/10090:Tsacc ^@ http://purl.uniprot.org/uniprot/Q9DA44 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the TSACC family.|||Co-chaperone that facilitates HSP-mediated activation of TSSK6.|||In testis, expressed in the inner luminal layer of the seminiferous tubules.|||Interacts with HSP70. Associates with HSP90. Interacts with TSSK6; this interaction is direct and recruits TSACC to HSP90 (By similarity). http://togogenome.org/gene/10090:Rsad2 ^@ http://purl.uniprot.org/uniprot/Q8CBB9 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ 'Lys-6'-linked polyubiquitination at Lys-207 leads to RSAD2 protein degradation.|||Acetylated by HAT1. HAT1-mediated acetylation of Lys-198 in turn recruits UBE4A that stimulates RSAD2 polyubiquitination leading to proteasomal degradation.|||Belongs to the radical SAM superfamily. RSAD2 family.|||Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.|||By interferon type I, type II and LPS. Induced by infection with Vesicular stomatitis virus and pseudorabies virus in dendritic cells, presumably through type I interferon pathway.|||Endoplasmic reticulum|||Endoplasmic reticulum membrane|||Expressed at higher levels in atherosclerotic arteries than in normal arteries.|||Golgi apparatus|||Homodimer. Interacts with IRAK1 and TRAF6 (PubMed:21435586). Interacts with FPPS. Interacts with HADHB. Interacts (via C-terminus) with VAPA/VAP33 (via C-terminus) (By similarity).|||IRAK1 and TRAF6 synergistically activate RSAD2 increasing its activity with CTP as substrate about 10-fold.|||Interferon-inducible antiviral protein which plays a major role in the cell antiviral state induced by type I and type II interferon. Catalyzes the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) via a SAM-dependent radical mechanism. In turn, ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple viruses and directly inhibits viral replication. Therefore, inhibits a wide range of DNA and RNA viruses (By similarity). Promotes also TLR7 and TLR9-dependent production of IFN-beta production in plasmacytoid dendritic cells (pDCs) by facilitating 'Lys-63'-linked ubiquitination of IRAK1 by TRAF6. Plays a role in CD4+ T-cells activation and differentiation. Facilitates T-cell receptor (TCR)-mediated GATA3 activation and optimal T-helper 2 (Th2) cytokine production by modulating NFKB1 and JUNB activities. Can inhibit secretion of soluble proteins (By similarity) (PubMed:17686841, PubMed:19047684, PubMed:21435586, PubMed:21880757).|||Lipid droplet|||Mitochondrion|||Mitochondrion inner membrane|||Mitochondrion outer membrane|||The N-terminal region (1-43) is necessary for its localization to the endoplasmic reticulum membrane and lipid droplet. http://togogenome.org/gene/10090:Or8b12c ^@ http://purl.uniprot.org/uniprot/Q7TRE4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Etnppl ^@ http://purl.uniprot.org/uniprot/Q8BWU8 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.|||Catalyzes the pyridoxal-phosphate-dependent breakdown of phosphoethanolamine, converting it to ammonia, inorganic phosphate and acetaldehyde.|||Does not seem to possess aminotransferase activity.|||Homotetramer.|||Mitochondrion http://togogenome.org/gene/10090:Slc16a1 ^@ http://purl.uniprot.org/uniprot/P53986|||http://purl.uniprot.org/uniprot/Q544N9 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Basolateral cell membrane|||Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.|||Bidirectional proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH (By similarity). The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (PubMed:22522610, PubMed:24367518). Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart. Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 302-Asp is essential for the conformational transition (PubMed:32946811).|||Cell membrane|||Complete lethality during early embryonic development. Heterozygous mice are viable and show no obvious morphological or behavorial phenotype. Heterozygous mice that are kept on a normal diet show normal weight gain, normal glucose tolerance and insulin sensitivity. In contrast, mice exhibit a striking reduction in weight gain relative to wild-type, when kept on a high-fat diet. This is due to reduced fat accumulation in the liver and in subcutaneous white adipose tissue. In addition, heterozygous mice kept on a high-fat diet show higher glucose tolerance and higher insulin sensitivity than wild-type. The reduced weight gain is explained by reduced food intake, less efficient nutrient assimilation in the intestine and increased oxygen consumption when kept on a high-fat diet. Besides, heterozygous mice fail to respond to a high-fat diet by up-regulation of genes involved in lipid metabolism.|||Detected in liver, brain, spinal cord, spermatozoa, muscle, white adipose tissue and brown adipose tissue (at protein level). Widely expressed, except in pancreas, where expression is not detectable.|||Interacts with isoform 2 of BSG; interaction mediates SLC16A1 targeting to the plasma membrane (PubMed:21792931). Interacts with EMB; interaction mediates SLC16A1 targeting to the plasma membrane (By similarity).|||Lateral cell membrane|||Membrane|||Overexpression in pancreatic beta-cells triggers insulin secretion in response to pyruvate, causing hyperinsulemia and hypoglycemia during strenuous exercise. http://togogenome.org/gene/10090:Papolb ^@ http://purl.uniprot.org/uniprot/A1L349|||http://purl.uniprot.org/uniprot/Q9WVP6 ^@ Cofactor|||Developmental Stage|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the poly(A) polymerase family.|||Binds 2 magnesium ions. Also active with manganese.|||Cytoplasm|||Expressed at low levels in 2-week-old mice. Abundantly expressed in 4-week-old and 6-week-old animals.|||Interacts with GSG1.|||Nucleus|||Testis specific. http://togogenome.org/gene/10090:Smyd2 ^@ http://purl.uniprot.org/uniprot/Q8R5A0 ^@ Caution|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Although specifically expressed in cardiomyocytes, a conditional deletion in heart does not lead to any visible phenotype.|||Belongs to the class V-like SAM-binding methyltransferase superfamily.|||Deletion within an exon that does not correspond to an intron.|||Highly expressed in heart, skeletal muscle and brain tissue. During cardiac development, it is differentially expressed with highest expression in the neonatal heart while very low expression is detected at 12.5 dpc and adult. Specifically expressed in cardiomyocytes (at protein level).|||Interacts (via MYND-type zinc finger) with EPB41L3. Interacts (via SET domain) with p53/TP53. Interacts with RB1 and HSP90AA1 (By similarity). Interacts with RNA polymerase II and HELZ. Interacts with SIN3A and HDAC1.|||Nucleus|||Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'.|||The protein was previously thought to dimethylate histone 3 'Lys-36', but this is now known not to take place in vivo.|||cytosol http://togogenome.org/gene/10090:Inpp5k ^@ http://purl.uniprot.org/uniprot/Q5ND43|||http://purl.uniprot.org/uniprot/Q8C5L6 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.|||Cytoplasm|||Endoplasmic reticulum|||Expressed in the skeletal muscle and the eye.|||Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Has 6-fold higher affinity for phosphatidylinositol 4,5-bisphosphate than for inositol 1,4,5-trisphosphate (By similarity). Negatively regulates assembly of the actin cytoskeleton. Controls insulin-dependent glucose uptake among inositol 3,4,5-trisphosphate phosphatases; therefore, is the specific regulator for insulin signaling in skeletal muscle (PubMed:22247557, PubMed:22751929).|||Interacts with GPR78; necessary for INPP5K localization at the endoplasmic reticulum. Interacts with PAK1; competes with GPR78. http://togogenome.org/gene/10090:Srl ^@ http://purl.uniprot.org/uniprot/Q7TQ48 ^@ PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.|||N-glycosylated.|||Sarcoplasmic reticulum lumen|||Sarcoplasmic reticulum membrane http://togogenome.org/gene/10090:Car10 ^@ http://purl.uniprot.org/uniprot/P61215|||http://purl.uniprot.org/uniprot/Q3V1V7 ^@ Function|||Similarity ^@ Belongs to the alpha-carbonic anhydrase family.|||Does not have a catalytic activity. http://togogenome.org/gene/10090:1700024G13Rik ^@ http://purl.uniprot.org/uniprot/Q3KNL4 ^@ Similarity ^@ Belongs to the UPF0728 family. http://togogenome.org/gene/10090:Dgkk ^@ http://purl.uniprot.org/uniprot/Q6DIC8 ^@ Similarity ^@ Belongs to the eukaryotic diacylglycerol kinase family. http://togogenome.org/gene/10090:Rab4b ^@ http://purl.uniprot.org/uniprot/Q4V9W8|||http://purl.uniprot.org/uniprot/Q91ZR1 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Protein transport.|||Serotonylation of Gln-67 by TGM2 during activation and aggregation of platelets leads to constitutive activation of GTPase activity.|||Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:14697203). Protein transport (By similarity). Probably involved in vesicular traffic (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (PubMed:14697203). http://togogenome.org/gene/10090:Rpl39l ^@ http://purl.uniprot.org/uniprot/Q9CQD0 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the eukaryotic ribosomal protein eL39 family.|||Component of a male germ cell-specific 60S large ribosomal subunit (LSU), which contains RPL10L and RPL39L, instead of RPL10 and RPL39 paralogs (PubMed:36517592). The composition of the rest of the complex is similar to classical ribosomes (PubMed:36517592).|||Cytoplasm|||Defective sperm formation, resulting in substantially reduced male fertility (PubMed:34825148, PubMed:36517592). Male mice show smaller testis sizes, lower testis/body weight ratio, increased ratios of abnormal sperm head and tail and severe subfertility with significantly fewer cumulative live pups born compared with wild-type mice (PubMed:36517592). The sperm count, motility and progressive motility are reduced (PubMed:36517592). Female mice display normal fertility (PubMed:36517592).|||Highly expressed in spermatocytes and spermatids (PubMed:34825148, PubMed:36517592). Highly expressed in embryonic stem cells (PubMed:24452241).|||Male germ cell-specific component of the ribosome, which is required for the formation of sperm and male fertility (PubMed:34825148, PubMed:36517592). Replaces the RPL39 paralog in the ribosome of male germ cells (PubMed:36517592). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:34428590, PubMed:36517592). The male germ cell-specific ribosome displays a ribosomal polypeptide exit tunnel of distinct size and charge states compared with the classical ribosome (PubMed:36517592). It is responsible for regulating the biosynthesis and folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm (PubMed:36517592). http://togogenome.org/gene/10090:Snx13 ^@ http://purl.uniprot.org/uniprot/E9QNG6|||http://purl.uniprot.org/uniprot/Q6PHS6 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the sorting nexin family.|||Early endosome membrane|||Embryonic lethal. After 8.5 dpc, embryos are smaller, show failure of neural tube closure and abnormal cephalic vascularization. None survive after 14.5 dpc. Visceral yolk sac endoderm cells contain large autophagic vacuoles.|||May be involved in several stages of intracellular trafficking. Acts as a GAP for Galphas (By similarity). May play a role in endosome homeostasis.|||The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate. http://togogenome.org/gene/10090:Mtch1 ^@ http://purl.uniprot.org/uniprot/Q791T5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Interacts with PSEN1.|||Mitochondrion outer membrane|||Protein insertase that mediates insertion of transmembrane proteins into the mitochondrial outer membrane (By similarity). Catalyzes insertion of proteins with alpha-helical transmembrane regions, such as signal-anchored, tail-anchored and multi-pass membrane proteins. Does not mediate insertion of beta-barrel transmembrane proteins (By similarity). May play a role in apoptosis (By similarity). http://togogenome.org/gene/10090:Diras2 ^@ http://purl.uniprot.org/uniprot/Q5PR73 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the small GTPase superfamily. Di-Ras family.|||Cell membrane|||Displays low GTPase activity and exists predominantly in the GTP-bound form. http://togogenome.org/gene/10090:Bhmt ^@ http://purl.uniprot.org/uniprot/O35490 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit ^@ Binds 1 zinc ion per subunit.|||Homotetramer.|||Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Wbp2nl ^@ http://purl.uniprot.org/uniprot/Q9D529 ^@ Function|||Tissue Specificity ^@ Expressed in testis.|||May play a role in meiotic resumption and pronuclear formation, mediated by a WW domain-signaling pathway during fertilization. http://togogenome.org/gene/10090:Ablim3 ^@ http://purl.uniprot.org/uniprot/Q69ZX8 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 15.5 dpc, expressed in skeletal muscle. Down-regulated in adult skeletal muscle.|||Cytoplasm|||Directly interacts with F-actin and ABRA.|||Expressed in heart, brain, lung and liver. In the brain, highly expressed in the olfactory bulb. In the hippocampus, expressed selectively in the CA2 and CA3 fields. In the cerebellum, expressed in internal granular cells.|||May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity. http://togogenome.org/gene/10090:Fgfr2 ^@ http://purl.uniprot.org/uniprot/E9Q5C2|||http://purl.uniprot.org/uniprot/E9Q7C7|||http://purl.uniprot.org/uniprot/E9QK53|||http://purl.uniprot.org/uniprot/P21803 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer (By similarity).|||Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Embryonic lethality shortly after implantation, due to trophoblast defects, absence of a functional placenta, failure of limb bud formation, plus defects in lung branching and heart development.|||Golgi apparatus|||Membrane|||Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF6, FGF7, FGF8, FGF9, FGF10, FGF17, FGF18 and FGF22 (in vitro) (PubMed:8663044). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19 and FGF21. Interacts with PLCG1 (PubMed:15629145). Interacts with GRB2 and PAK4 (By similarity). Interacts with FLRT2 (PubMed:21765038).|||N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus (By similarity).|||Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).|||The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Alternative splicing events affecting the third Ig-like domain are crucial for ligand selectivity (By similarity).|||Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.|||Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome (By similarity). http://togogenome.org/gene/10090:Rab2a ^@ http://purl.uniprot.org/uniprot/P53994 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small GTPase superfamily. Rab family.|||Endoplasmic reticulum membrane|||Endoplasmic reticulum-Golgi intermediate compartment membrane|||Golgi apparatus membrane|||Interacts with PRKCI. Interacts with TRIP11. Interacts (in GTP-bound form) with GARIN1B (PubMed:34714330).|||Melanosome|||Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology. Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi.|||acrosome http://togogenome.org/gene/10090:Myoz2 ^@ http://purl.uniprot.org/uniprot/Q9JJW5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc, expressed weakly in heart. Higher levels of expression detected at 12.5 dpc and 15.5 dpc in both cardiac and skeletal muscle.|||Belongs to the myozenin family.|||Expressed specifically in heart and skeletal muscle. In skeletal muscle, localized to the soleus and plantaris muscles, which are predominantly composed of slow-twitch fibers.|||Interacts via its C-terminus with spectrin repeats 3 and 4 of ACTN2. Interacts with ACTN1, LDB3, MYOT and PPP3CA (By similarity).|||Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.|||Z line http://togogenome.org/gene/10090:Or4x15 ^@ http://purl.uniprot.org/uniprot/A2ATW2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Bnip2 ^@ http://purl.uniprot.org/uniprot/O54940 ^@ Function|||Subcellular Location Annotation ^@ Cytoplasm|||Implicated in the suppression of cell death. Interacts with the BCL-2 and adenovirus E1B 19 kDa proteins (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Slc51b ^@ http://purl.uniprot.org/uniprot/Q80WK2 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the OST-beta family.|||Cell membrane|||Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood (PubMed:15563450, PubMed:16317684, PubMed:17650074, PubMed:22535958). The Ost-alpha/Ost-beta complex efficiently transports the major species of bile acids (taurocholate) (PubMed:16317684, PubMed:17650074, PubMed:22535958). Taurine conjugates are transported more efficiently across the basolateral membrane than glycine-conjugated bile acids (PubMed:16317684). Can also transport steroids such as estrone 3-sulfate and dehydroepiandrosterone 3-sulfate, therefore playing a role in the enterohepatic circulation of sterols (By similarity). Able to transport eicosanoids such as prostaglandin E2 (By similarity). Modulates SLC51A glycosylation, membrane trafficking and stability activities (PubMed:15563450).|||Interacts with SLC51A. The Ost-alpha/Ost-beta complex is a heterodimer composed of alpha (SLC51A) and beta (SLC51B) subunit; induces the transport of SLC51A from the reticulum endoplasmic to the plasma membrane.|||Positively regulated via the bile acid-activated nuclear receptor farnesoid X receptor (NR1H4/FXR).|||Present at high level in ileum. In ileum, it is restricted to the apical domain on the mature villus enterocytes with little detectable expression in the goblet cells or crypt enterocytes (at protein level). Expressed in kidney but not in heart, brain, liver, spleen, embryo, lung, thymus, ovary nor testis.|||The transmembrane domain (TM) is the major site of interaction with SLC51A. The extracellular-membrane interface is absolutely required for transport activity. The intracellular-membrane interface is necessary for establishing the correct membrane orientation that is essential for the heterodimer Ost-alpha/Ost-beta complex formation and transport activity at the cell membrane surface. http://togogenome.org/gene/10090:Ang2 ^@ http://purl.uniprot.org/uniprot/Q64438|||http://purl.uniprot.org/uniprot/W0UV59 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the pancreatic ribonuclease family.|||Divalent metal ions, such as Cu2+ and Zn2+, may inhibit the ribonucleolytic activity.|||Expressed (at protein level) in macrophages.|||Has ribonuclease activity (in vitro). Seems to lack angiogenic activity.|||Homodimer.|||Secreted|||nucleolus|||secretory vesicle lumen http://togogenome.org/gene/10090:Pot1b ^@ http://purl.uniprot.org/uniprot/H7BX60 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the telombin family.|||Nucleus|||telomere http://togogenome.org/gene/10090:Mrgprg ^@ http://purl.uniprot.org/uniprot/Q91ZB5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||Orphan receptor. May regulate nociceptor function and/or development, including the sensation or modulation of pain. http://togogenome.org/gene/10090:Rnase10 ^@ http://purl.uniprot.org/uniprot/E9QPU5|||http://purl.uniprot.org/uniprot/G3UWD1|||http://purl.uniprot.org/uniprot/Q9D5A9 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the pancreatic ribonuclease family.|||Expressed in mature epididymis.|||Male-specific expression in proximal caput of the epididymis (at protein level).|||Mice are viable, anatomically normal and reach adulthood but display impaired fertility consequent to an inability of the spermatozoa to ascend the uterotubal junction (UTJ) canal of the female reproductive tract and gain the site of fertilization. Spermatozoa fail to establish a strong association with either epididymal epithelial cells, the zona pellucida of oocytes or oviductal epithelial cells, yet they are capable of fertilizing eggs in vitro.|||Secreted|||Secreted proximal epididymal protein required for post-testicular sperm maturation and male fertility. May be involved in sperm adhesion to the egg zona pellucida. Does not have ribonuclease activity.|||The N-terminus is blocked. Glycosylated (By similarity). http://togogenome.org/gene/10090:Ncoa1 ^@ http://purl.uniprot.org/uniprot/P70365 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SRC/p160 nuclear receptor coactivator family.|||Contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors. LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro.|||Interacts with PPARA; the interaction is direct (By similarity). Interacts with PPARG; the interaction is direct (By similarity). Interacts with ESRRG; the interaction is direct (By similarity). Interacts with STAT5A (via FDL motif) (By similarity). Interacts with STAT5B (via FDL motif) (By similarity). Interacts with STAT6 (via LXXLL motif) (PubMed:14757047). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif) (PubMed:16148126). Interacts with ASXL1 (By similarity). Interacts with the methyltransferase CARM1 (PubMed:10381882). Interacts with COPS5 (By similarity). Interacts with the histone acetyltransferase CREBBP (PubMed:8616895). Interacts with DDX5 (By similarity). Interacts with the histone acetyltransferase EP300 (PubMed:8616895, PubMed:8855229). Interacts with ESR1 (By similarity). Interacts with GCCR (By similarity). Interacts with the basal transcription factor GTF2B (By similarity). Interacts with NCOA6 (By similarity). Interacts with NCOA2 (By similarity). Interacts with NR3C1 (By similarity). Interacts with NR4A1/Nur77 (By similarity). Interacts with NR4A3 (PubMed:12709428). Interacts with PCAF (By similarity). Interacts with PGR (By similarity). Interacts with PRMT2 (By similarity). Interacts with PRMT6 (By similarity). Interacts with PSMB9 (By similarity). Interacts with RXRA, the interaction is ligand-dependent (By similarity). Interacts with STAT3 following IL-6 stimulation (By similarity). Interacts with TRA (By similarity). Interacts with TRIP4 (By similarity). Interacts with TTLL5/STAMP (By similarity). Interacts with UBE2L3; they functionally interact to regulate progesterone receptor transcriptional activity (By similarity). Interacts with VDR (By similarity).|||Mice show partial hormone resistance: target organs such as uterus, prostate, testis and mammary gland exhibiting decreased growth and development in response to steroid hormones. Moreover, such mice are prone to obesity due to reduced energy expenditure.|||Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.|||Nucleus|||Sumoylated; sumoylation increases its interaction with PGR and prolongs its retention in the nucleus. It does not prevent its ubiquitination and does not exert a clear effect on the stability of the protein (By similarity).|||The C-terminal (1113-1447) part mediates the histone acetyltransferase (HAT) activity.|||Ubiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites (By similarity).|||Widely expressed. http://togogenome.org/gene/10090:Galnt12 ^@ http://purl.uniprot.org/uniprot/Q60GT3|||http://purl.uniprot.org/uniprot/Q8BGT9 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.|||Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has activity toward non-glycosylated peptides such as Muc5AC, Muc1a and EA2, and no detectable activity with Muc2 and Muc7. Displays enzymatic activity toward the Gal-NAc-Muc5AC glycopeptide, but no detectable activity to mono-GalNAc-glycosylated Muc1a, Muc2, Muc7 and EA2. May play an important role in the initial step of mucin-type oligosaccharide biosynthesis in digestive organs (By similarity).|||Golgi apparatus membrane|||Membrane|||The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.|||There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. http://togogenome.org/gene/10090:Pcdhgc4 ^@ http://purl.uniprot.org/uniprot/Q91XX0 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Atp10a ^@ http://purl.uniprot.org/uniprot/O54827|||http://purl.uniprot.org/uniprot/Q3V1Y7|||http://purl.uniprot.org/uniprot/Q6A046 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated at the conserved aspartate of the P-type ATPase signature sequence.|||Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.|||Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane. Initiates inward plasma membrane bending and recruitment of Bin/amphiphysin/Rvs (BAR) domain-containing proteins involved in membrane tubulation and cell trafficking. Facilitates ITGB1/beta1 integrin endocytosis, delaying cell adhesion and cell spreading on extracellular matrix. Has low flippase activity toward glucosylceramide (GlcCer).|||Cell membrane|||Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP10A and an accessory beta subunit TMEM30A.|||Endoplasmic reticulum membrane|||Found in testis and in white adipose tissue. Also detected in fetal tissues.|||Membrane http://togogenome.org/gene/10090:Blnk ^@ http://purl.uniprot.org/uniprot/Q9QUN3 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2 (By similarity). Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-120' (PubMed:21930792, PubMed:28290451).|||Cell membrane|||Cytoplasm|||Expressed in the spleen and weakly in thymus, no expression was seen in liver, testis, or brain. Expressed in B-cell lines representing different developmental stages from the pre-B to the plasma cell stage, but not in a T-cell or a fibroblast cell line.|||Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca(2+) and MAPK signaling pathways (By similarity). Phosphorylation of Tyr-96 is required for the binding of BTK.|||Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis. http://togogenome.org/gene/10090:Zfp516 ^@ http://purl.uniprot.org/uniprot/Q7TSH3 ^@ Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Expressed by adipocytes more specifically in brown adipose tissue compared to white adipose tissue (WAT).|||Interacts with PRDM16; the interaction is direct and may play a role in the transcription of brown adipose tissue-specific genes (PubMed:25578880). Interacts with PWWP2B (PubMed:34180153). Interacts with HDAC1; this interaction is enhanced in the presence of PWWP2B (PubMed:34180153).|||Knockout mice die immediately after birth. 20.5 dpc embryos display an impaired development of brown adipose tissue.|||Nucleus|||Transcriptional regulator that binds to the promoter and activates the transcription of genes promoting brown adipose tissue (BAT) differentiation. Among brown adipose tissue-specific genes, binds the proximal region of the promoter of the UCP1 gene to activate its transcription and thereby regulate thermogenesis. May also play a role in the cellular response to replication stress (By similarity).|||Up-regulated in response to cold in brown and subcutaneous white adipose tissue where it may regulate non-shivering thermogenesis (at protein level). http://togogenome.org/gene/10090:Mtpn ^@ http://purl.uniprot.org/uniprot/P62774 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the myotrophin family.|||Cytoplasm|||Interacts with RELA (By similarity). Interacts with the heterodimer formed by CAPZA1 and CAPZB.|||Nucleus|||Promotes dimerization of NF-kappa-B subunits and regulates NF-kappa-B transcription factor activity. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy (By similarity). Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex formed by the CAPZA1 and CAPZB heterodimer.|||perinuclear region http://togogenome.org/gene/10090:H2al1m ^@ http://purl.uniprot.org/uniprot/Q9DAD9 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the histone H2A family.|||Nucleus|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Dhps ^@ http://purl.uniprot.org/uniprot/Q3TXU5 ^@ Function|||Similarity ^@ Belongs to the deoxyhypusine synthase family.|||Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a critical lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. This is the first step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function. http://togogenome.org/gene/10090:Skint8 ^@ http://purl.uniprot.org/uniprot/A7XV07 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SKINT family.|||Encoded by one of the 11 copies of Skint genes clustered in the D1 region of the chromosome 4.|||Expressed in skin, thymus, testis and, to a lower extent, bladder, brain, heart, kidney, mammary gland, small intestine and uterus.|||May act by engaging a cell surface molecule on immature T-cells in the embryonic thymus.|||Membrane http://togogenome.org/gene/10090:Or52b1 ^@ http://purl.uniprot.org/uniprot/Q8VH18 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Or5d43 ^@ http://purl.uniprot.org/uniprot/Q7TR24 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Slc30a8 ^@ http://purl.uniprot.org/uniprot/Q8BGG0 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.|||Cell membrane|||Each subunit of the homodimer independently transports zinc ions in a pH-dependent manner. The cytosolic pH promotes binding of zinc ions to the transporter binding site. Upon change into the organelle-facing conformation, the two histidines of the zinc-binding site get protonated at lumenal lower pH, triggering zinc release into the organelle. The transporter then moves back to the cytosolic-facing conformation where the two histidines get deprotonated at higher pH, resulting in a net antiport of 2 protons.|||Expressed in endocrine pancreatic islet alpha and beta cells. Not detected in the brain.|||Homodimer.|||Knockout mice lacking Slc30a8 do not display overt developmental, morphological or behavioral phenotypes. However, a significant difference in plasma insulin concentration is observed.|||Proton-coupled zinc ion antiporter mediating the entry of zinc into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion.|||secretory vesicle membrane http://togogenome.org/gene/10090:Slc29a4 ^@ http://purl.uniprot.org/uniprot/Q8R139 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated at acidic pH.|||Apical cell membrane|||Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.|||Cell membrane|||Electrogenic voltage-dependent transporter that mediates the transport of a variety of endogenous bioactive amines, cationic xenobiotics and drugs (PubMed:16873718, PubMed:23255610). Utilizes the physiologic inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations (By similarity). Functions as a Na(+)- and Cl(-)-independent bidirectional transporter (By similarity). Substrate transport is pH-dependent and enhanced under acidic condition, which is most likely the result of allosteric changes in the transporter structure (PubMed:16873718). Implicated in monoamine neurotransmitters uptake such as serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system (PubMed:23255610). Also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, thereby playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain (PubMed:23255610). Involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia (PubMed:16873718). May be involved in organic cation uptake from the tubular lumen into renal tubular cells, thereby contributing to organic cation reabsorption in the kidney (PubMed:23255610). Also transports adenine and guanidine (PubMed:16873718).|||Expressed in heart (PubMed:16873718). Expressed in choroid plexus (PubMed:23255610).|||Glu-206 is essential for cation selectivity and may function as the charge sensor for cationic substrates.|||Knockout mice are viable, fertile with no overt physiological abnormalities. Knockout mice show an impaired uptake of serotonin and dopamine in choroid plexus.|||N-glycosylated.|||Other than a moderate activity for adenosine, PMAT does not interact with nucleosides, nucleobases, or nucleotides (By similarity). Mediates the uptake of clinically used drugs including neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) (PubMed:23255610). http://togogenome.org/gene/10090:Fscn1 ^@ http://purl.uniprot.org/uniprot/Q61553 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Actin-binding protein that contains 2 major actin binding sites (By similarity). Organizes filamentous actin into parallel bundles (PubMed:7738015). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (By similarity). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:21685497). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (By similarity).|||Belongs to the fascin family.|||Cell junction|||Composed of four fascin beta-trefoil domains.|||Interacts with RUFY3 (via N-terminus); the interaction induces neuron axon development (PubMed:24720729). Interacts with NGFR (By similarity). Associates with CTNNB1 (PubMed:8794867). Interacts with PLXNB3 (PubMed:21706053).|||Most abundant in brain. Detected at lower levels in lung, uterus, small intestine and spleen (at protein level).|||Phosphorylation at Ser-39 inhibits actin-binding. Phosphorylation is required for the reorganization of the actin cytoskeleton in response to NGF.|||cell cortex|||cytoskeleton|||cytosol|||filopodium|||growth cone|||invadopodium|||microvillus|||stress fiber http://togogenome.org/gene/10090:Agbl1 ^@ http://purl.uniprot.org/uniprot/D3Z1M2|||http://purl.uniprot.org/uniprot/Q09M05 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase M14 family.|||Binds 1 zinc ion per subunit.|||Interacts with MYLK (PubMed:21074048). Interacts with TCF4 (By similarity).|||Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins (PubMed:21074048). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein (PubMed:21074048). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:21074048). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK (PubMed:21074048).|||Widely expressed at low level. Expressed in eye, muscle, pituitary, testis and to a lower extent in brain.|||cytosol http://togogenome.org/gene/10090:Vmn1r254 ^@ http://purl.uniprot.org/uniprot/K7N6J2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Plbd2 ^@ http://purl.uniprot.org/uniprot/Q3TCN2 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the phospholipase B-like family.|||Glycosylated; contains mannose 6-phosphate sugars.|||Interacts with IGF2R.|||Lysosome lumen|||Present at highest levels in spleen, lung and brain (at protein level).|||Putative phospholipase.|||The p76 protein is synthesized as a 76 kDa precursor which is then processed into a N-terminal 28 kDa form and a C-terminal 40 kDa form. The C-terminal peptide is further processed into a 15 kDa form. http://togogenome.org/gene/10090:Eri3 ^@ http://purl.uniprot.org/uniprot/Q8C460 ^@ Cofactor|||Subunit|||Tissue Specificity ^@ Binds 2 magnesium ions per subunit.|||Highly expressed in the brain, heart, thyroid and testis. Expressed at low levels in the muscle cells, liver, pancreas and kidney.|||Interacts with PRNP. http://togogenome.org/gene/10090:Dact3 ^@ http://purl.uniprot.org/uniprot/Q0PHV7 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the dapper family.|||Can form homodimers and heterodimers with DACT1 or DACT3. Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, DVL1, DVL2, DVL3, VANGL1, VANGL2 and CTNND1.|||Expressed in brain and uterus.|||Expression peaks at 10.5 dpc, then declines. Expressed in the ventral region of maturing somites, limb bud and branchial arch mesenchyme, and in the developing central nervous system.|||May be involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins (By similarity).|||The C-terminal PDZ-binding motif may mediate interaction with the PDZ domains of DSH (Dishevelled) family proteins. http://togogenome.org/gene/10090:Stx6 ^@ http://purl.uniprot.org/uniprot/Q9JKK1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the syntaxin family.|||Golgi apparatus membrane|||Identified in a complex containing STX6, STX12 and VAMP4 (By similarity). This complex also includes VTI1A (PubMed:9705316). Binds EEA1 (By similarity). Interacts with VPS45A and GOPC (By similarity). Interacts with MARCHF2; the interaction promotes MARCHF2-mediated ubiquitination and degradation of CFTR (By similarity). Interacts with MARCHF3 (By similarity). Interacts with BLTP3B (via C-terminal coiled-coil domain) (PubMed:35499567). Interacts with BAIAP3; this interaction is increased in the presence of calcium (By similarity). Interacts with VPS13B (By similarity).|||Recycling endosome membrane|||SNARE promoting movement of transport vesicles to target membranes. Targets endosomes to the trans-Golgi network, and may therefore function in retrograde trafficking. Together with SNARE STX12, promotes movement of vesicles from endosomes to the cell membrane, and may therefore function in the endocytic recycling pathway.|||trans-Golgi network membrane http://togogenome.org/gene/10090:Hspb2 ^@ http://purl.uniprot.org/uniprot/Q6P3C8|||http://purl.uniprot.org/uniprot/Q99PR8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the small heat shock protein (HSP20) family.|||Cytoplasm|||Interacts with DMPK; may enhance its kinase activity.|||May regulate the kinase DMPK.|||Nucleus http://togogenome.org/gene/10090:Amy2a5 ^@ http://purl.uniprot.org/uniprot/P00688 ^@ Cofactor|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyl hydrolase 13 family.|||Binds 1 Ca(2+) ion per subunit.|||Binds 1 Cl(-) ion per subunit.|||Monomer.|||extracellular space http://togogenome.org/gene/10090:Sorbs1 ^@ http://purl.uniprot.org/uniprot/Q62417 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell membrane|||Expressed in all tissues tested: heart, brain, spleen, lung, liver, muscle, kidney and testis. Expressed in 3T3-L1 adipocytes but not in 3T3-L1 fibroblasts.|||Interacts (via SH3 domain 2) with PXN (By similarity). Interacts with the long isoform of AFDN and with VCL. AFDN and VCL bind to SORBS1 in a competitive manner and do not form a ternary complex. Interacts with ABL1, CBL, CBLB and INPPL1/SHIP2 through the third SH3 domain. Interaction with ABL1 occurs only after insulin stimulation while this has no effect on the interaction with INPPL1. Interacts with the insulin receptor but dissociates from it following insulin stimulation. Also interacts with SCA7, PTK2/FAK1 and flotillin. Interacts (via third SH3 domain) with the Ten-1 ICD form of TENM1; the interaction induces the translocation of SORBS1 to the nucleus. Interacts with INSM1.|||Nucleus|||Nucleus matrix|||O-glycosylated.|||Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions.|||adherens junction|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Eif2a ^@ http://purl.uniprot.org/uniprot/Q8BJW6 ^@ Caution|||Function|||Similarity ^@ Belongs to the WD repeat EIF2A family.|||Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner.|||This gene should not be confused with EIF2S1, frequently called eIF2-alpha in the literature, and with which it shares the alias EIF2A. EIF2S1 is the alpha subunit of the eIF2 translation initiation complex. Although both of these proteins function in binding initiator tRNA to the 40S ribosomal subunit, the EIF2A protein does so in a codon-dependent manner, whereas eIF2 complex requires GTP. http://togogenome.org/gene/10090:Bcl2l2 ^@ http://purl.uniprot.org/uniprot/P70345 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Bcl-2 family.|||By Igf1.|||Expressed in almost all myeloid cell lines and in a wide range of tissues, with highest levels in brain, colon, and salivary gland.|||Expressed in both mitotic and postmitotic Sertoli cells.|||Interacts with HIF3A isoform 2 (via C-terminus domain) (PubMed:21546903). Interacts with BOP (By similarity).|||Mice are sterile due to arrest in spermatogenesis associated with a gradual loss of germ and Sertoli cells from the testis.|||Mitochondrion membrane|||Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.|||The BH1 and BH2 motifs form a hydrophobic groove which acts as a docking site for the BH3 domain of some pro-apoptotic proteins. The C-terminal residues of BCL2L2 fold into the BH3-binding cleft and modulate pro-survival activity by regulating ligand access. When BH3 domain-containing proteins bind, they displace the C-terminus, allowing its insertion into the membrane and neutralizing the pro-survival activity of BCL2L2 (By similarity).|||The BH4 motif seems to be involved in the anti-apoptotic function. http://togogenome.org/gene/10090:Mon2 ^@ http://purl.uniprot.org/uniprot/B9EKJ3|||http://purl.uniprot.org/uniprot/Q80TL7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MON2 family.|||Early endosome membrane|||Homooligomer. Heterotrimer with ATP9A and DOP1B; this interaction is retromer-independent. Interacts with SNX3.|||Membrane|||Plays a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation. http://togogenome.org/gene/10090:Glb1l2 ^@ http://purl.uniprot.org/uniprot/A0A0R4J0L1|||http://purl.uniprot.org/uniprot/E0CYE1|||http://purl.uniprot.org/uniprot/Q3UPY5|||http://purl.uniprot.org/uniprot/Q8BZW3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyl hydrolase 35 family.|||Secreted http://togogenome.org/gene/10090:Tdo2 ^@ http://purl.uniprot.org/uniprot/P48776|||http://purl.uniprot.org/uniprot/Q8VCW3 ^@ Caution|||Cofactor|||Function|||Similarity|||Subunit ^@ Belongs to the tryptophan 2,3-dioxygenase family.|||Binds 1 heme group per subunit.|||Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety.|||Homotetramer. Dimer of dimers.|||Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Or8g52 ^@ http://purl.uniprot.org/uniprot/Q7TRA7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Dis3 ^@ http://purl.uniprot.org/uniprot/Q9CSH3 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RNR ribonuclease family.|||Component of the RNA exosome complex (By similarity). The catalytically inactive RNA exosome core (Exo-9) complex is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms (By similarity). Interacts with DHX34; the interaction is RNA-independent (By similarity).|||Cytoplasm|||Incompletely spliced mRNA.|||Nucleus|||Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. DIS3 has both 3'-5' exonuclease and endonuclease activities.|||nucleolus|||nucleoplasm http://togogenome.org/gene/10090:Tbx20 ^@ http://purl.uniprot.org/uniprot/Q9ES03 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a transcriptional activator and repressor required for cardiac development and may have key roles in the maintenance of functional and structural phenotypes in adult heart.|||Between 7.25 dpc and 8 dpc, expression detected in the extraembryonic mesoderm and contributes to amnion and chorion. Allantois expression persists until 10.5 dpc and continues into the umbilical cord. Expression is found throughout heart development. At 7.5 dpc, detected in the cardiogenic mesoderm, at 8.0 dpc-8.5, found in the cardiac crescent and looping heart tube and from 9.5 dpc, found in the forming four-chambered heart. At all stages, expression is much stronger in the myocardium than in the endocardium and expression extends from the cardiogenic into the lateral plate mesoderm. From 10.5 dpc on, weakly expressed in the periphery of the liver lobes, and in cells surrounding the aorta in the urogenital system. At 9.0 dpc, weakly expressed in the dorsal half of the optic vesicle. Later, expression spreads ventrally to enclose the entire neural retina at 11.5 dpc. At 9.0 dpc, expression is initiated in the hindbrain: first in the ventral region of rhombomere (r) 2 and 4, then in r7, r8 and in the cervical spinal cord. By 10.5 dpc, two ventral stripes of Tbx20 containing cells are continuous from r2 into the cervical spinal cord and expression is seen in two symmetrical patches of cell bodies in the mantle region of the ventral neural tube. At 11.5 dpc, expression follows the migration of motor neurons.|||Embryos die at mid-gestation. The heart tube of deficient mice does not elongate, but anterior and secondary heart field markers are not affected.|||Nucleus|||Prominently expressed in the extraembryonic mesoderm, developing heart, eye analage and motor neurons of hindbrain and spinal cord. Expressed in extraembryonic tissues such as the amnion and allantois. http://togogenome.org/gene/10090:Abra ^@ http://purl.uniprot.org/uniprot/Q8BUZ1 ^@ Developmental Stage|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an activator of serum response factor (SRF)-dependent transcription possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling.|||At 8.75 dpc, expressed in the primitive heart tube. Thereafter, expression is maintained in heart and is also detected in skeletal muscle after 10.5 dpc.|||Binds F-actin and ABLIM1, ABLIM2 and ABLIM3. Interaction with ABLIM2 and ABLIM3 enhances activity.|||Expressed specifically in heart and skeletal muscle.|||The actin-binding domain 1 (ABD1) is intrinsically disordered, and binds to F-actin with higher affinity than ABD2.|||cytoskeleton|||sarcomere http://togogenome.org/gene/10090:Or4f58 ^@ http://purl.uniprot.org/uniprot/Q8VET0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Endou ^@ http://purl.uniprot.org/uniprot/Q3V188 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ENDOU family.|||Endoribonuclease that cleaves single-stranded RNAs at 5' of uridylates and releases a product with a 2',3'-cyclic phosphate at the 3'-end. The UU and GU sites are more efficiently cleaved than CU and AU sites.|||Monomer.|||Secreted|||Specifically expressed in T-cells during apoptosis. Expressed in surface heat stable antigen (HSA)-containing T-cells populations (CD4(-)CD8(-)HSA(+), CD4(+)CD8(-)HSA(+), CD4(-)CD8(+)HSA(+), and CD4(+)CD8(+)HSA(+)) and not in the HSA(-) single positive T-cell populations of the thymus or spleen, suggesting that expression is lost during T-cell maturation and is absent at the most mature stages of T-cell development. http://togogenome.org/gene/10090:Tln2 ^@ http://purl.uniprot.org/uniprot/E9PUM4|||http://purl.uniprot.org/uniprot/Q71LX4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ As a major component of focal adhesion plaques that links integrin to the actin cytoskeleton, may play an important role in cell adhesion. Recruits PIP5K1C to focal adhesion plaques and strongly activates its kinase activity (By similarity).|||Cell membrane|||Cytoplasm|||Interacts directly with PIP5K1C.|||Synapse|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:Chchd7 ^@ http://purl.uniprot.org/uniprot/Q8K2Q5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CHCHD7 family.|||Mitochondrion intermembrane space|||Monomer. http://togogenome.org/gene/10090:Ubn1 ^@ http://purl.uniprot.org/uniprot/Q4G0F8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as a novel regulator of senescence. Involved in the formation of senescence-associated heterochromatin foci (SAHF), which represses expression of proliferation-promoting genes. Binds to proliferation-promoting genes. May be required for replication-independent chromatin assembly (By similarity).|||Belongs to the ubinuclein family.|||Component of a complex that includes at least ASF1A, CABIN1, HIRA, histone H3.3 and UBN1. Interacts with HIRA (via WD repeat domain); the interaction is direct. Interacts with ASF1A, CEBPA, TJP1, TJP2 and TJP3 (By similarity).|||Expressed in bile canaliculi in liver, in bronchiolar epithelium in lung and in tubular structures of gland ducts inside the olfactory epithelium and tongue epithelium.|||PML body|||nucleoplasm|||tight junction http://togogenome.org/gene/10090:Spats2 ^@ http://purl.uniprot.org/uniprot/Q8K1N4 ^@ Developmental Stage|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the SPATS2 family.|||Cytoplasm|||Detected in newborns. Levels increase during the first four weeks, and then remain at the same stable level.|||Detected in testis, in spermatocytes and round spermatids (at protein level). Highly expressed in testis, and detected at lower levels in brain, heart, thymus, skeletal muscle, ovary, stomach and lung. http://togogenome.org/gene/10090:Gpr3 ^@ http://purl.uniprot.org/uniprot/P35413 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in both the forebrain and hindbrain, with the highest level in habenula. Lower level expression in the testis. Highly expressed in regions.|||Mice are fertile but display progressive reduction in litter size despite a stable age-independent alteration of the meiotic pause, characterized by premature resumption of meiosis in about one-third of antral follicles in mutant females regardless of age. Aging mutant mice had severe reduction of fertility, manifested by an increasing number of nondeveloping early embryos upon spontaneous ovulation and massive amounts of fragmented oocytes after superovulation.|||Orphan receptor with constitutive G(s) signaling activity that activate cyclic AMP. Has a potential role in modulating a number of brain functions, including behavioral responses to stress, amyloid-beta peptide generation in neurons (By similarity) and neurite outgrowth (By similarity). Maintains also meiotic arrest in oocytes. http://togogenome.org/gene/10090:Csnk2a2 ^@ http://purl.uniprot.org/uniprot/O54833|||http://purl.uniprot.org/uniprot/Q545V8 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein kinase superfamily.|||Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.|||Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome.|||Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins.|||Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization (By similarity).|||Cytoplasm|||Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1 (By similarity). Interacts with CSNKA2IP (via C-terminus) (PubMed:19273531). Interacts with SIRT6; preventing CSNK2A2 localization to the nucleus (PubMed:28355567).|||Highly expressed in brain, testis and mature epididymal spermatozoa. Weakly expressed in kidney, liver, lung, spleen and thymus (at protein level).|||Infertile male mice with oligospermia and globozoospermia.|||Nucleus http://togogenome.org/gene/10090:Jph2 ^@ http://purl.uniprot.org/uniprot/Q9ET78 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in skeletal muscle and heart (PubMed:10949023). Weak expression in stomach and lung (PubMed:10949023).|||At 9.5 dpc, it is expressed in the periphery of cardiac myocytes in the looped cardiac tube of the developing heart (PubMed:10949023). In skeletal muscle, expression increases during muscle maturation (PubMed:10949023).|||Belongs to the junctophilin family.|||Cell membrane|||Endoplasmic reticulum membrane|||Interacts with MEF2C (PubMed:30409805).|||Interacts with TRPC3 (By similarity). Interacts with BAG5 and HSPA8; the interaction with HSPA8 is increased in the presence of BAG5 (By similarity).|||Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes (PubMed:10949023, PubMed:19095005, PubMed:21339484). Provides a structural foundation for functional cross-talk between the cell surface and intracellular Ca(2+) release channels by maintaining the 12-15 nm gap between the sarcolemma and the sarcoplasmic reticulum membranes in the cardiac dyads (PubMed:10949023, PubMed:19095005, PubMed:21339484). Necessary for proper intracellular Ca(2+) signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release (PubMed:10949023, PubMed:19095005, PubMed:21339484). Contributes to the construction of skeletal muscle triad junctions (PubMed:10949023).|||Nucleus|||Null mice possess cardiomyocytes with deficiencies in the junctional membrane complexes and have abnormal Ca(2+) transients (PubMed:10949023, PubMed:19095005, PubMed:21339484). Mice die from cardiac arrest at 10.5 dpc (PubMed:10949023).|||Phosphorylation on Ser-165, probably by PKC, affects RYR1-mediated calcium ion release, interaction with TRPC3, and skeletal muscle myotubule development.|||Proteolytically cleaved by calpain in response to cardiac stress (PubMed:26063807). The major cleavage site takes place at the C-terminus and leads to the release of the Junctophilin-2 N-terminal fragment chain (JP2NT) (PubMed:26063807, PubMed:30409805).|||Sarcoplasmic reticulum membrane|||The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, by interacting with phospholipids. Has affinity for phosphatidylserine, and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P, PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3.|||The bipartite nuclear localization signal (bNLS) and Ala-rich (alanine-rich; ARR) regions are involved in DNA-binding.|||Transcription repressor required to safeguard against the deleterious effects of cardiac stress (PubMed:30409805). Generated following cleavage of the Junctophilin-2 chain by calpain in response to cardiac stress in cardiomyocytes (PubMed:30409805). Following cleavage and release from the membrane, translocates to the nucleus, binds DNA and represses expression of genes implicated in cell growth and differentiation, hypertrophy, inflammation and fibrosis (PubMed:30409805). Modifies the transcription profile and thereby attenuates pathological remodeling in response to cardiac stress (PubMed:30409805). Probably acts by competing with MEF2 transcription factors and TATA-binding proteins (PubMed:30409805). http://togogenome.org/gene/10090:Tom1 ^@ http://purl.uniprot.org/uniprot/O88746|||http://purl.uniprot.org/uniprot/Q3UDC3|||http://purl.uniprot.org/uniprot/Q561M4 ^@ Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways (By similarity). Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (By similarity). Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (By similarity). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (By similarity). Binds to polyubiquitinated proteins via its GAT domain (By similarity). In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (By similarity). The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (By similarity). Mediates clathrin recruitment to early endosomes by ZFYVE16 (By similarity). Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns(3)P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking (By similarity). Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation (PubMed:25588840). PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation (PubMed:25588840). Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (By similarity).|||Belongs to the TOM1 family.|||Cytoplasm|||Early endosome membrane|||Endosome membrane|||Found in a complex with TOLLIP; interacts (via GAT domain) with TOLLIP (via N-terminus); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns(3)P (By similarity). Interacts (via GAT domain and the C-terminal part of the VHS domain) with UBC/ubiquitin (By similarity). Interacts (via clathrin box and C-terminus) with clathrin heavy chain (By similarity). Interacts with MYO6 (By similarity). Interacts with TAX1BP1; CALCOCO2/NDP52 and OPTN; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and the three autophagy receptors (By similarity). Interacts (via C-terminus) with ZFYVE16 (via C-terminus); interaction is required to target TOM1 and clathrin to endosomes (By similarity). Interacts with LRBA (By similarity).|||Monoubiquitinated.|||The GAT domain and the VHS domain are required for the interaction with polyubiquitinated proteins.|||The VHS domain binds to phosphatidylinositol monophosphates (By similarity). The KRKK motif within the VHS domain is required for binding to phosphatidylinositol monophosphates, with a preference for phosphatidylinositol 5-phosphate (PtdIns(5)P) (By similarity).|||Ubiquitous. In adult brain, it is highly expressed at the mesencephalic level, in the hippocampal formation and medial lemniscus. In cerebellum, it is highly expressed in Purkinje cells and granular layers.|||Ubiquitously expressed in the embryo, with a higher expression in the intestines. http://togogenome.org/gene/10090:Phyhip ^@ http://purl.uniprot.org/uniprot/B9EIC7|||http://purl.uniprot.org/uniprot/Q8K0S0 ^@ Developmental Stage|||Function|||Miscellaneous|||Similarity|||Subunit|||Tissue Specificity ^@ At 18 dpc, expressed in most tissues, particularly in the skin. By neonatal day 1, the expression in brain and skin is markedly increased, whereas expression in the heart and skeletal muscles shows steady state levels similar to those observed in the fetus. At adulthood, very high expression in brain, little or no expression in other tissues.|||Belongs to the PHYHIP family.|||Highly expressed in the brain.|||Interacts with PHYH and ADGRB1.|||Its interaction with PHYH suggests a role in the development of the central system.|||Overexpression in heart induce atrial tachycardia and increased susceptibility to aconitine-induced arrhythmia, possibly due to altered expression of voltage-gated K(1+) channel and adrenergic beta1-receptor (ADRB1). http://togogenome.org/gene/10090:H60b ^@ http://purl.uniprot.org/uniprot/B1B212 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the NKG2D ligand family.|||Cell membrane|||In strain C57BL/6J, strongly expressed in cardiac muscle and skeletal muscle, with lower expression levels in spleen, liver, kidney and thymus. In strain BALB/cJ, weakly expressed in cardiac muscle, spleen, kidney and thymus.|||Ligand for the KLRK1 immunosurveillance receptor. Binding to KLRK1 stimulates cell lysis in vitro.|||Up-regulated in response to infection by murine cytomegalovirus. http://togogenome.org/gene/10090:Or52ae9 ^@ http://purl.uniprot.org/uniprot/Q0VBH3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Gpat4 ^@ http://purl.uniprot.org/uniprot/Q8K2C8 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) by incorporating an acyl moiety at the sn-1 position of the glycerol backbone (PubMed:18238778). Active against both saturated and unsaturated long-chain fatty acyl-CoAs (By similarity). Protects cells against lipotoxicity (By similarity).|||Endoplasmic reticulum membrane|||Highly expressed in testis.|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate. http://togogenome.org/gene/10090:V1ra8 ^@ http://purl.uniprot.org/uniprot/Q9EQ48 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in a subset of sensory neurons located in the apical layer of the vomeronasal organ.|||Mice lacking all but one V1ra and V1rb gene (12% of the V1r repertoire) show a lack of chemosensory response to a subset of known pheromonal ligands and changes in maternal aggression as well as male reproductive behavior.|||Putative pheromone receptor implicated in the regulation of social and reproductive behavior. http://togogenome.org/gene/10090:Frem2 ^@ http://purl.uniprot.org/uniprot/Q6NVD0 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FRAS1 family.|||Cell membrane|||Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia (By similarity). Required for epidermal adhesion (PubMed:15838507). Involved in the development of eyelids and the anterior segment of the eyeballs (PubMed:30802441).|||First expressed from 10 dpc in the mesodermal core of the branchial arches, developing lens, otic vesicle and limb apical ectodermal ridge. Later, it is expressed in the vibrissae and vibrissae pad, eyelids ear and pelage follicles and, at low levels, in the epidermis (PubMed:15838507). Also expressed in caudal somites and, in later embryos, in facial, limb and intercostal muscles (PubMed:15838507). In contrast to Frem1, it is not expressed in the developing mammary glands or in the caecum (PubMed:15838507). Restricted to the epithelia in a pattern complementary to that of Frem1 (which is generally expressed in the dermis and mesenchyme) (PubMed:15838507). In the developing kidney, it is expressed At in the mesonephric and metanephric epithelia at 11.5 dpc, with a highest expression at the tips of the developing ureteric buds (PubMed:15838507). At 12.5 and 13.5 dpc, it is still expressed throughout the epithelial components of the kidney, including epithelia fated to form nephrons, which are induced by the ureter tips to differeintiate from the mesenchymal condensations that surround them (PubMed:15838507). Expressed in retinal neuron-containing outer plexiform layer (PubMed:30802441).|||Interacts with FREM1.|||Mice display cryptophthalmos, syndactyly and renal defects. Frem2 corresponds to the X-ray irradiated-induced allele 'myelencephalic blebs' (my).|||The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding. http://togogenome.org/gene/10090:Tcl1b1 ^@ http://purl.uniprot.org/uniprot/P56840|||http://purl.uniprot.org/uniprot/Q3UWQ4 ^@ Similarity ^@ Belongs to the TCL1 family. http://togogenome.org/gene/10090:Vmac ^@ http://purl.uniprot.org/uniprot/Q8BP01 ^@ Subcellular Location Annotation ^@ Cytoplasm http://togogenome.org/gene/10090:Pnldc1 ^@ http://purl.uniprot.org/uniprot/B2RXZ1 ^@ Caution|||Developmental Stage|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ 3'-exoribonuclease that has a preference for poly(A) tails of mRNAs, thereby efficiently degrading poly(A) tails (PubMed:27515512). Exonucleolytic degradation of the poly(A) tail is often the first step in the decay of eukaryotic mRNAs and is also used to silence certain maternal mRNAs translationally during oocyte maturation and early embryonic development (PubMed:27515512). May act as a regulator of multipotency in embryonic stem cells (PubMed:27515512). Is a critical factor for proper spermatogenesis, involved in pre-piRNAs processing to generate mature piRNAs (By similarity).|||Belongs to the CAF1 family.|||Down-regulated in differentiated cells, due to methylation of its promoter by the methyltransferase DNMT3B.|||Endoplasmic reticulum membrane|||Expressed during early embryo development and fades during differentiation.|||Preliminary results in vitro suggested that Pnldc1 might act as an exonuclease that specifically cleaves precursor piRNAs (pre-piRNAs) at their 3' ends (PubMed:26919431). These results however require additional experimental evidences: another report showed that the protein mainly localizes to the endoplasmic reticulum and preferentially acts on poly(A) tails (PubMed:27515512).|||Specifically expressed in embryonic stem cells (PubMed:27515512). Highly expressed in testis (PubMed:26919431, PubMed:27515512). http://togogenome.org/gene/10090:Hsd3b1 ^@ http://purl.uniprot.org/uniprot/P24815|||http://purl.uniprot.org/uniprot/Q3UI20|||http://purl.uniprot.org/uniprot/Q3UJ12 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ A bifunctional enzyme responsible for the oxidation and isomerization of 3beta-hydroxy-Delta(5)-steroid precursors to 3-oxo-Delta(4)-steroids, an essential step in steroid hormone biosynthesis. Specifically catalyzes the conversion of pregnenolone to progesterone, 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone, dehydroepiandrosterone (DHEA) to 4-androstenedione, and androstenediol to testosterone. Additionally, catalyzes the interconversion between 3beta-hydroxy and 3-oxo-5alpha-androstane steroids controlling the bioavalability of the active forms. Specifically converts dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Also converts androstanedione, a precursor of testosterone and estrone, to epiandrosterone. Expected to use NAD(+) as preferred electron donor for the 3-beta-hydroxy-steroid dehydrogenase activity and NADPH for the 3-ketosteroid reductase activity.|||Belongs to the 3-beta-HSD family.|||Endoplasmic reticulum membrane|||Mitochondrion membrane|||Steroidogenic tissues (includes testes, ovaries and adrenal glands). http://togogenome.org/gene/10090:Mios ^@ http://purl.uniprot.org/uniprot/Q8VE19 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:35022234). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (By similarity). GATOR2 probably acts as a E3 ubiquitin-protein ligase toward GATOR1 (By similarity). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (By similarity). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (By similarity). Within the GATOR2 complex, MIOS is required to prevent autoubiquitination of WDR24, the catalytic subunit of the complex (By similarity). The GATOR2 complex is required for brain myelination (PubMed:35022234).|||Belongs to the WD repeat mio family.|||Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. CASTOR1 and CASTOR2 convey leucine availability via direct interaction with MIOS. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids.|||Embryonic lethality around 9 dpc (PubMed:35022234). Conditional deletion in neural stem cells specifically impairs the formation of myelinating oligodendrocytes, thus brain myelination, without effecting the formation of neurons and astrocytes (PubMed:35022234).|||Lysosome membrane|||The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.|||Widely expressed (PubMed:35022234). In brain, expressed in neurons and glia (oligodendrocytes and astrocytes), with more abundance in neurons (PubMed:35022234). http://togogenome.org/gene/10090:Cers2 ^@ http://purl.uniprot.org/uniprot/Q924Z4 ^@ Activity Regulation|||Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated (PubMed:26620563). Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation (PubMed:26620563).|||Broadly expressed, with highest levels in liver and kidney (PubMed:15823095, PubMed:18165233, PubMed:19801672). In brain is detected in neurons, oligodentrocytes, ependymal cells and epithelial cells of the choroid plexus. In kidney is detected in collecting ducts and to a lesser degree in proximal tubules.|||Ceramide synthase activity is inhibited by sphingosine-1-phosphate.|||Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward very-long-chain fatty acyl-CoA (chain length C22-C27) (PubMed:15823095, PubMed:18165233, PubMed:20110363, PubMed:23275342). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:15823095, PubMed:18165233, PubMed:20110363, PubMed:23275342). Plays a non-redundant role in the synthesis of ceramides with very-long-chain fatty acids in kidney, liver and brain. Regulates the abundance of myelin-specific sphingolipids galactosylceramide and sulfatide that affects myelin sheath architecture and motor neuron functions (PubMed:19801672, PubMed:32279995).|||Contains a predicted homeobox domain which is degenerated and lacks residues that are important for DNA-binding. The protein localizes in the endoplasmic reticulum and not in the nucleus, which also argues against homeobox function (PubMed:15823095).|||Endoplasmic reticulum membrane|||Interacts with ATP6V0C, ASGR1, ASGR2 and SLC22A1/OCT1. Interacts with ELOV1, HSD17B12 and TECR (By similarity). Interacts with NDUFS2 (PubMed:32279995).|||Most mice do not survive beyond 16 months (PubMed:20110363). Ceramide and downstream sphingolipids are devoid of very long (C22-C24) acyl chains (PubMed:20110363). Total glycerophospholipid and cholesterol levels are unaltered, while a marked increase in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids are observed (PubMed:20110363). Membranes display higher membrane fluidity and show morphological changes (PubMed:20110363). Mutant mice show signs of neurodegeneration characterized by the loss of myelin sheath structure stability and formation of numerous small cysts in the cerebellum. They develop hepatocarcinomas between 7 and 9 months of age.|||Phosphorylated at the C-terminus by CK2, leading to increase the ceramide synthase activity.|||The last loop motif confers selectivity toward behenoyl-CoA (docosanoyl-CoA; C22:0-CoA) and lignoceroyl-CoA (tetracosanoyl-CoA; C24:0-CoA) as acyl donors. http://togogenome.org/gene/10090:Mamdc2 ^@ http://purl.uniprot.org/uniprot/Q8CG85 ^@ Developmental Stage|||PTM|||Subcellular Location Annotation ^@ At 16.5 dpc, present in rib cartilage (at protein level).|||O-glycosylated; contains chondroitin sulfate.|||extracellular matrix http://togogenome.org/gene/10090:Apol6 ^@ http://purl.uniprot.org/uniprot/B7ZC54|||http://purl.uniprot.org/uniprot/B7ZC55|||http://purl.uniprot.org/uniprot/Q3UN08|||http://purl.uniprot.org/uniprot/Q9D6L7 ^@ Similarity ^@ Belongs to the apolipoprotein L family. http://togogenome.org/gene/10090:Cd300c2 ^@ http://purl.uniprot.org/uniprot/Q7TSN2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts as an activating receptor in mast cells and macrophages.|||Belongs to the CD300 family.|||Cell membrane|||Interacts with TYROBP, HCST and FcR gamma.|||Present on the surface of mast cells, dendritic cells, peritoneal macrophages and a subset of B-cells (at protein level). http://togogenome.org/gene/10090:Fam174b ^@ http://purl.uniprot.org/uniprot/Q8K064 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM174 family.|||Cell membrane|||Essential for Golgi structural integrity.|||Golgi apparatus http://togogenome.org/gene/10090:Cysltr2 ^@ http://purl.uniprot.org/uniprot/Q920A1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4.|||Widely expressed at low levels, with highest expression in the spleen, thymus and adrenal gland, and lower in the kidney, brain and peripheral blood leukocytes. http://togogenome.org/gene/10090:Erlin1 ^@ http://purl.uniprot.org/uniprot/Q91X78 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the band 7/mec-2 family.|||Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. Binds cholesterol and may promote ER retention of the SCAP-SREBF complex (By similarity).|||Endoplasmic reticulum membrane|||Forms a heteromeric complex with ERLIN2 (By similarity). In complex with ERLIN2, interacts with RNF170 (PubMed:21610068). Interacts with AMFR and SYVN1 (By similarity). http://togogenome.org/gene/10090:Ly6l ^@ http://purl.uniprot.org/uniprot/H3BJG9 ^@ Subcellular Location Annotation ^@ Cell membrane http://togogenome.org/gene/10090:Tlr11 ^@ http://purl.uniprot.org/uniprot/Q6R5P0|||http://purl.uniprot.org/uniprot/V9GWT0 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the Toll-like receptor family.|||Binds MYD88 via their respective TIR domains (By similarity). Interacts with HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:20865800).|||In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.|||Membrane|||Participates in the innate immune response to microbial agents. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.|||There is some confusion regarding the nomenclature of this gene. In the literature, Tlr11 is frequently referred to as Tlr12 and vice-versa. http://togogenome.org/gene/10090:Cnp ^@ http://purl.uniprot.org/uniprot/P16330|||http://purl.uniprot.org/uniprot/Q3TYL9|||http://purl.uniprot.org/uniprot/Q3TYV5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the 2H phosphoesterase superfamily. CNPase family.|||Catalyzes the formation of 2'-nucleotide products from 2',3'-cyclic substrates (By similarity). May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin (PubMed:22393399).|||Exists as monomers and homodimers.|||May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin.|||Melanosome|||Membrane http://togogenome.org/gene/10090:Fam217a ^@ http://purl.uniprot.org/uniprot/Q9D9W6 ^@ Similarity ^@ Belongs to the FAM217 family. http://togogenome.org/gene/10090:Foxh1 ^@ http://purl.uniprot.org/uniprot/O88621|||http://purl.uniprot.org/uniprot/Q0VEP8 ^@ Developmental Stage|||Domain|||Function|||Miscellaneous|||Subcellular Location Annotation|||Subunit ^@ Expressed predominantly throughout the epiblast before gastrulation and declines as development progresses.|||Fails to bind DNA and cannot confer activin response element responsiveness.|||Interacts with the MH2 domains of SMAD2 and SMAD3.|||Nucleus|||The FM region is required for binding SMAD2/SMAD4 complexes. FM2 is more effective than FM1 and only interacts with phosphorylated SMAD2 that is in an activated SMAD complex (By similarity).|||Transcriptional activator. Recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. Required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signaling. Forms a transcriptionally active complex containing FOXH1/SMAD2/SMAD4 on a site on the GSC promoter called TARE (TGF-beta/activin response element). http://togogenome.org/gene/10090:Cd200r1 ^@ http://purl.uniprot.org/uniprot/Q9ES57 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD200R family.|||CD200 and CD200R1 interact via their respective N-terminal Ig-like domains.|||Cell membrane|||Expressed in granulocytes, monocytes, most T-cells and a subset of NK, NKT and B-cells (at protein level). Expressed in the spleen, lung, liver, testis, bone marrow, lymph nodes, spinal cord, kidney, uterus and small intestine. Expressed in mast and dendritic cells. Expressed in the lung of N. brasiliensis-infected mice.|||Inhibitory receptor for the CD200/OX2 cell surface glycoprotein. Limits inflammation by inhibiting the expression of pro-inflammatory molecules including TNF-alpha, interferons, and inducible nitric oxide synthase (iNOS) in response to selected stimuli.|||May be expressed in adult splenic cells (PubMed:15187158), as the antibody used could not discriminate between CD200R1 and CD200R4. May be expressed in uterus at 12.5 dpc (at protein level) (PubMed:15274657), as the antibody used could not discriminate between CD200R1 and CD200R4. http://togogenome.org/gene/10090:Or4k42 ^@ http://purl.uniprot.org/uniprot/Q7TQX8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Ndufa4 ^@ http://purl.uniprot.org/uniprot/Q62425 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex IV NDUFA4 subunit family.|||Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (By similarity). Interacts with RAB5IF (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding.|||Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. NDUFA4 is required for complex IV maintenance.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:H2bc22 ^@ http://purl.uniprot.org/uniprot/Q8CGP2 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The human orthologous protein seems not to exist.|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Klk1 ^@ http://purl.uniprot.org/uniprot/P15947 ^@ Function|||Similarity ^@ Belongs to the peptidase S1 family. Kallikrein subfamily.|||Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin. http://togogenome.org/gene/10090:Bet1 ^@ http://purl.uniprot.org/uniprot/O35623 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the BET1 family.|||Endoplasmic reticulum membrane|||Golgi apparatus membrane|||Interacts with STX17.|||Required for vesicular transport from the ER to the Golgi complex. Functions as a SNARE involved in the docking process of ER-derived vesicles with the cis-Golgi membrane (By similarity).|||cis-Golgi network membrane http://togogenome.org/gene/10090:Mrpl52 ^@ http://purl.uniprot.org/uniprot/Q9D0Y8 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrion-specific ribosomal protein mL52 family.|||Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Rpap1 ^@ http://purl.uniprot.org/uniprot/Q80TE0 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the RPAP1 family.|||Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. Required for interaction of the RNA polymerase II complex with acetylated histone H3 (By similarity).|||Nucleus|||Part of an RNA polymerase II complex that contains POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, RPAP1, FCP1 plus the general transcription factors TFIIB and TFIIF. http://togogenome.org/gene/10090:Cdc23 ^@ http://purl.uniprot.org/uniprot/Q8BGZ4 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the APC8/CDC23 family.|||Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).|||Phosphorylated. Phosphorylation on Thr-562 occurs specifically during mitosis (By similarity).|||The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5. Interacts with FBXO43; the interaction is direct. http://togogenome.org/gene/10090:Tmem64 ^@ http://purl.uniprot.org/uniprot/Q3U145 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TVP38/TMEM64 family.|||Endoplasmic reticulum|||Interacts with ATP2A2 (PubMed:23395171).|||Liver, testis, kidney and muscle.|||Membrane|||Mice exhibit increased bone mass due in part to impaired osteoclast formation. Bones show reduced osteoclast numbers (PubMed:23395171). Increased osteogenesis and impaired adipogenesis observed in bone marrow-derived stromal cells (PubMed:25979161).|||Positively regulates TNFSF11-induced osteoclast differentiation. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with SERCA2 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation (PubMed:23395171). Negatively regulates osteoblast differentiation and positively regulates adipocyte differentiation via modulation of the canonical Wnt signaling pathway. Mediates the switch in lineage commitment to osteogenesis rather than to adipogenesis in mesenchymal stem cells by negatively regulating the expression, activity and nuclear localization of CTNNB1 (PubMed:25979161).|||The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain. http://togogenome.org/gene/10090:Cntn2 ^@ http://purl.uniprot.org/uniprot/Q61330 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the immunoglobulin superfamily. Contactin family.|||Cell membrane|||In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region. http://togogenome.org/gene/10090:Mrpl1 ^@ http://purl.uniprot.org/uniprot/Q99N96|||http://purl.uniprot.org/uniprot/Q9D3F3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the universal ribosomal protein uL1 family.|||Mitochondrion http://togogenome.org/gene/10090:Vps51 ^@ http://purl.uniprot.org/uniprot/Q3UVL4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome-derived carriers to the TGN. Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane.|||Belongs to the VPS51 family.|||Component of the Golgi-associated retrograde protein (GARP) complex, also called VFT (VPS fifty-three) complex, composed of VPS51, VPS52, VPS53 and VPS54 (By similarity). Component of the endosome-associated retrograde protein (EARP) complex, composed of VPS51, VPS52, VPS53 and VPS50/Syndetin (By similarity). EIPR1 interacts with both EARP and GARP complexes and mediates the recruitment of the GARP complex to the trans-Golgi network (By similarity). Interacts with STX6 (via N-terminus) (PubMed:30962439). Interacts with VPS50 and VPS54 in an EIPR1-independent manner (By similarity).|||Recycling endosome|||trans-Golgi network http://togogenome.org/gene/10090:Ssr3 ^@ http://purl.uniprot.org/uniprot/Q4FK79|||http://purl.uniprot.org/uniprot/Q9DCF9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRAP-gamma family.|||Endoplasmic reticulum membrane|||Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma.|||Membrane|||TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. http://togogenome.org/gene/10090:Gfer ^@ http://purl.uniprot.org/uniprot/P56213 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen (By similarity).|||Homodimer; disulfide-linked. Interacts with CHCHD4/MIA40.|||Mitochondrion|||Mitochondrion intermembrane space|||Preferentially expressed in the liver and in testis. http://togogenome.org/gene/10090:Smarcd2 ^@ http://purl.uniprot.org/uniprot/Q3TXH6|||http://purl.uniprot.org/uniprot/Q99JR8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMARCD family.|||Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B), and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (ACTB). Interacts with UNKL. Interacts with CEBPE.|||Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation.|||Nucleus|||Ubiquitinated through a signaling process involving RAC1 and the RING finger protein UNKL. http://togogenome.org/gene/10090:0610010K14Rik ^@ http://purl.uniprot.org/uniprot/Q9DCT6 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of chromatin complexes such as the MLL1/MLL and NURF complexes.|||Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the nucleosome-remodeling factor (NURF) complex (By similarity).|||Nucleus http://togogenome.org/gene/10090:Smim1 ^@ http://purl.uniprot.org/uniprot/P0C8K7 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SMIM1 family.|||Cell membrane|||Homooligomer; disulfide-linked.|||Regulator of red blood cell formation. http://togogenome.org/gene/10090:Eif3m ^@ http://purl.uniprot.org/uniprot/Q99JX4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eIF-3 subunit M family.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.|||Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.|||Cytoplasm http://togogenome.org/gene/10090:Ncr1 ^@ http://purl.uniprot.org/uniprot/Q8C567 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the natural cytotoxicity receptor (NCR) family.|||Cell membrane|||Cytotoxicity-activating receptor that may contribute to the increased efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.|||Interacts with CD3Z and FCER1G.|||Selectively expressed by NK cells. http://togogenome.org/gene/10090:Chmp7 ^@ http://purl.uniprot.org/uniprot/Q8R1T1 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SNF7 family.|||Cytoplasm|||ESCRT-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope (NE) during late anaphase (By similarity). Together with SPAST, the ESCRT-III complex promotes NE sealing and mitotic spindle disassembly during late anaphase (By similarity). Recruited to the reforming NE during anaphase by LEMD2 (By similarity). Plays a role in the endosomal sorting pathway (By similarity).|||Interacts with CHMP4B, but not with VPS25 (By similarity). Interacts with LEMD2 (via C-terminus) (By similarity).|||Nucleus envelope http://togogenome.org/gene/10090:Mterf2 ^@ http://purl.uniprot.org/uniprot/Q8BKY8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mTERF family.|||Binds mitochondrial DNA and plays a role in the regulation of transcription of mitochondrial mRNA and rRNA species.|||Monomer.|||mitochondrion nucleoid http://togogenome.org/gene/10090:Fhl3 ^@ http://purl.uniprot.org/uniprot/Q9R059 ^@ Developmental Stage|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in myogenic progenitor cells (at protein level) (PubMed:17363903). Expressed in skeletal striated muscle and the heart (PubMed:10906474, PubMed:17363903). Expressed to a lesser extent, in lung, and kidney (PubMed:10906474). Expressed in skin and skeletal muscles such as the masseter, tongue, tibialis anterior and plantar muscles (PubMed:10049693).|||Expressed ubiquitously at low levels during embryonic development.|||Interacts with SOX15; the interaction recruits FHL3 to FOXK1 promoters where it acts as a transcriptional coactivator of FOXK1.|||Nucleus|||Recruited by SOX15 to FOXK1 promoters where it acts as a transcriptional coactivator of FOXK1. http://togogenome.org/gene/10090:Elf2 ^@ http://purl.uniprot.org/uniprot/Q3TVH6|||http://purl.uniprot.org/uniprot/Q9JHC9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the ETS family.|||Expressed in all tissues examined. Highest levels in thymocytes and bone marrow.|||Interacts with LIM domains of LMO2. Interacts via its N-terminal region with RUNX1.|||Nucleus|||Probably transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter. http://togogenome.org/gene/10090:Tcn2 ^@ http://purl.uniprot.org/uniprot/O88968 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the eukaryotic cobalamin transport proteins family.|||Interacts with CD320 (via LDL-receptor class A domains).|||Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells.|||Secreted http://togogenome.org/gene/10090:Rbp4 ^@ http://purl.uniprot.org/uniprot/H7BWY6|||http://purl.uniprot.org/uniprot/Q00724 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the calycin superfamily. Lipocalin family.|||Interacts with TTR. Interaction with TTR prevents its loss by filtration through the kidney glomeruli. Interacts with STRA6.|||Retinol-binding protein that mediates retinol transport in blood plasma. Delivers retinol from the liver stores to the peripheral tissues. Transfers the bound all-trans retinol to STRA6, that then facilitates retinol transport across the cell membrane.|||Secreted http://togogenome.org/gene/10090:Ctdsp2 ^@ http://purl.uniprot.org/uniprot/Q8BX07 ^@ Cofactor|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Binds 1 Mg(2+) ion per monomer.|||Expression is restricted to non-neuronal tissues.|||Monomer. Interacts with REST.|||Nucleus|||Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells (By similarity). http://togogenome.org/gene/10090:Tac1 ^@ http://purl.uniprot.org/uniprot/B7ZMQ2|||http://purl.uniprot.org/uniprot/P41539|||http://purl.uniprot.org/uniprot/Q149W7 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation ^@ Belongs to the tachykinin family.|||Secreted|||Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.|||The substance P form is cleaved at Pro-59 by the prolyl endopeptidase FAP (seprase) activity (in vitro). Substance P is also cleaved and degraded by Angiotensin-converting enzyme (ACE) and neprilysin (MME). http://togogenome.org/gene/10090:Vmn1r176 ^@ http://purl.uniprot.org/uniprot/G3UW31 ^@ Caution|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Osr1 ^@ http://purl.uniprot.org/uniprot/Q9WVG7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the Odd C2H2-type zinc-finger protein family.|||During early embryogenesis it is expressed in the intermediate mesoderm and in a dynamic pattern during limb and branchial arch development. Is expressed from the earliest stage of intermediate development. Is expressed in the dorsal atrial wall, including the developing primary atrial septum and the venous valve.|||Mice die prenatally with severe heart defects including defective atrioventricular junction and venous valves. They never initiate metanephric kidney formation. Nephrogenic mesenchyme undergo massive apoptosis, which causes a disruption of nephric duct elongation and failure of metanephric induction.|||Nucleus|||Transcription factor that plays a role in the regulation of embryonic heart and urogenital development.|||Transcriptionally regulated by Ikzf1 and Runx2. http://togogenome.org/gene/10090:Plaat3 ^@ http://purl.uniprot.org/uniprot/Q8R3U1 ^@ Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ (Microbial infection) Acts as a host factor for picornaviruses: required during early infection to promote viral genome release into the cytoplasm (PubMed:28077878).|||Belongs to the H-rev107 family.|||Cell membrane|||Cytoplasm|||Endoplasmic reticulum membrane|||Exhibits both phospholipase A1/2 and acyltransferase activities (PubMed:19047760). Shows phospholipase A1 (PLA1) and A2 (PLA2), catalyzing the calcium-independent release of fatty acids from the sn-1 or sn-2 position of glycerophospholipids (PubMed:18614531, PubMed:19047760, PubMed:19136964, PubMed:22134920). For most substrates, PLA1 activity is much higher than PLA2 activity (By similarity). Shows O-acyltransferase activity, catalyzing the transfer of a fatty acyl group from glycerophospholipid to the hydroxyl group of lysophospholipid (By similarity). Shows N-acyltransferase activity,catalyzing the calcium-independent transfer of a fatty acyl group at the sn-1 position of phosphatidylcholine (PC) and other glycerophospholipids to the primary amine of phosphatidylethanolamine (PE), forming N-acylphosphatidylethanolamine (NAPE), which serves as precursor for N-acylethanolamines (NAEs) (PubMed:19047760). Exhibits high N-acyltransferase activity and low phospholipase A1/2 activity (By similarity). Required for complete organelle rupture and degradation that occur during eye lens terminal differentiation, when fiber cells that compose the lens degrade all membrane-bound organelles in order to provide lens with transparency to allow the passage of light (PubMed:33854238). Organelle membrane degradation is probably catalyzed by the phospholipase activity (PubMed:33854238).|||Interacts with PPP2R1A; this interaction might decrease PP2A activity.|||Lysosome membrane|||Mice display resistance to diet-induced obesity: they show strongly reduced adipose tissue mass and triglyceride content but normal adipogenesis accompanied by higher energy expenditure and increased fatty acid oxidation in adipocytes (PubMed:19136964). Mice show resistance to infection by picornaviruses, such as coxsackievirus A10, probably due to reduced viral genome release into the host cytoplasm (PubMed:28077878). The eye lens of knockout animals shows no growth defect, but the degradation of mitochondria, the endoplasmic reticulum and lysosomes is almost completely suppressed at postnatal day 0.5 and at 2 months and membranous organelles persisted at this time point (PubMed:33854238).|||Mitochondrion membrane|||Nucleus envelope|||Peroxisome membrane|||The C-terminal transmembrane domain is required for the targeting of the protein to damaged organelles.|||Ubiquitously expressed in normal tissues but down-regulated in primary carcinomas or in many cell lines derived from tumors (PubMed:12055182). Highly expressed in white adipose tissue and in adipocytes (PubMed:18614531, PubMed:19136964). Expressed at lower levels in brown adipose tissue (PubMed:18614531, PubMed:19136964).|||cytosol|||perinuclear region http://togogenome.org/gene/10090:Cyp1a2 ^@ http://purl.uniprot.org/uniprot/B6VGH4|||http://purl.uniprot.org/uniprot/P00186 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit ^@ A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid. Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer. Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin. Metabolizes caffeine via N3-demethylation.|||Belongs to the cytochrome P450 family.|||By 3-methylcholanthrene (3MC).|||Cytochromes P450 are a group of heme-thiolate monooxygenases. They oxidize a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.|||Endoplasmic reticulum membrane|||Interacts with PGRMC1; the interaction requires PGRMC1 homodimerization.|||Membrane|||Microsome membrane http://togogenome.org/gene/10090:Stk26 ^@ http://purl.uniprot.org/uniprot/Q99JT2 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.|||Cytoplasm|||Golgi apparatus|||Homodimer. Interacts with PDCD10. Interacts with GOLGA2. Interacts with CTTNBP2NL. Interacts with RIPOR1 (via C-terminus); this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts with PDCD10; this interaction is required for the association of STK26 with RIPOR1.|||Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-178, possibly as a consequence of stabilization of dimer formation. May also be activated by C-terminal cleavage (By similarity).|||Serine/threonine-protein kinase that acts as a mediator of cell growth. Modulates apoptosis. In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation. Phosphorylates ATG4B at 'Ser-383', thereby increasing autophagic flux. http://togogenome.org/gene/10090:Ppp1r3a ^@ http://purl.uniprot.org/uniprot/Q99MR9 ^@ Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Interacts with PPP1CC catalytic subunit of PP1, and associates with glycogen.|||Membrane|||Phosphorylation at Ser-48 by ISPK stimulates the dephosphorylation of glycogen synthase and phosphorylase kinase.|||Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase.|||Skeletal muscle and heart.|||The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes. http://togogenome.org/gene/10090:Igsf21 ^@ http://purl.uniprot.org/uniprot/Q7TNR6 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in brain (at protein levels) (PubMed:28864826). Highly expressed in the pyramidal cell layer of the dorsal and ventral hippocampal CA1 and CA3 regions, layers 5 and 6 of the cortex, the thalamus and the pons and weakly expressed in the cerebellum (PubMed:28864826). Expressed in neurons but not in glia (PubMed:28864826).|||Expressed in the brain at both embryonic and postnatal stages including the adult stage. The period of highest expression of the long isoform is at around two postnatal weeks, coinciding with the peak period of synaptogenesis.|||Ig-like 1 domain is indispensable for synaptogenic activity whereas Ig-like 2 domain is secondarily responsible for the activity.|||Interacts (Ig-like 1 domain) with NRXN2 (via Laminin G-like 1 domain) in a trans-interaction manner.|||Involved in synaptic inhibition in the brain. Selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic NRXN2.|||Mutants grow normally. They show an impaired sensorimotor gating with no effect on motor activity and coordination.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Parva ^@ http://purl.uniprot.org/uniprot/Q3UF75|||http://purl.uniprot.org/uniprot/Q9EPC1 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the parvin family.|||Cell membrane|||Embryonic lethality, due to severe cardiovascular defects causing whole body edema and severe bleeding due to vessel rupture. Embryos show defects in the septation of the heart outflow tract. Their cardiomyocytes are round and fail to align in a parallel manner. Blood vessels are frequently enlarged and show numerous microaneurisms. Besides, blood vessels show abnormal constrictions and increased vascular sprouting. Vascular mural cells and pericytes display a rounded shape and impaired adhesion to the underlying vascular endothelium. Cells display highly dynamic formation of membrane ruffles with increased random motility, but impaired chemotaxis.|||Interacts with TGFB1I1 (PubMed:11134073). Interacts with LIMS1 (via LD motifs) (By similarity). Interacts with ARHGAP31 (PubMed:16860736). Interacts with the actin cytoskeleton (PubMed:11134073). Interacts (via C-terminus) with ILK (By similarity). Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction inhibits TESK1 kinase activity (By similarity). Interacts with PXN/PAXILLIN (via LD motif 4) (PubMed:11134073).|||Membrane|||Plays a role in sarcomere organization and in smooth muscle cell contraction. Required for normal development of the embryonic cardiovascular system, and for normal septation of the heart outflow tract. Plays a role in sprouting angiogenesis and is required for normal adhesion of vascular smooth muscle cells to endothelial cells during blood vessel development. Plays a role in the reorganization of the actin cytoskeleton, formation of lamellipodia and ciliogenesis. Plays a role in the establishment of cell polarity, cell adhesion, cell spreading, and directed cell migration.|||Z line|||cytoskeleton|||focal adhesion http://togogenome.org/gene/10090:S100a6 ^@ http://purl.uniprot.org/uniprot/P14069|||http://purl.uniprot.org/uniprot/Q545I9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the S-100 family.|||Cell membrane|||Cytoplasm|||Homodimer; head to tail assembly of 2 subunits. Interacts with CACYBP in a calcium-dependent manner. Interacts with ANXA2 and ANXA11 (via N-terminus). Interacts with SUGT1. Interacts with TP53; has higher affinity for TP53 that is phosphorylated on its N-terminal domain, and lower affinity for TP53 that is phosphorylated on its C-terminal domain. Interacts with tropomyosin. Interacts with FKBP4. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with TPPP; this interaction inhibits TPPP dimerization (By similarity).|||May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes such as the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative (By similarity).|||May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes such as the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative.|||Nucleus envelope http://togogenome.org/gene/10090:Reep1 ^@ http://purl.uniprot.org/uniprot/Q8BGH4 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the DP1 family.|||Detected in olfactory sensory neurons of the olfactory epithelium, and in total brain.|||Endoplasmic reticulum|||Interacts with OLFR992 (PubMed:15550249). Interacts with SPAST and ATL1. Interacts (via C-terminus) with microtubules (By similarity). Interacts with ZFYVE27 (PubMed:24668814).|||Membrane|||Mitochondrion membrane|||Required for endoplasmic reticulum (ER) network formation, shaping and remodeling; it links ER tubules to the cytoskeleton. May also enhance the cell surface expression of odorant receptors (By similarity). http://togogenome.org/gene/10090:H2bc4 ^@ http://purl.uniprot.org/uniprot/Q6ZWY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Scgb1b7 ^@ http://purl.uniprot.org/uniprot/D2XZ31 ^@ Subcellular Location Annotation ^@ Secreted http://togogenome.org/gene/10090:Pcdha9 ^@ http://purl.uniprot.org/uniprot/Q91Y11 ^@ Function|||Miscellaneous|||Subcellular Location Annotation ^@ Cell membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.|||The protocadherins alpha are expressed from a single gene cluster similarly to immunoglobulin and T-cell receptors. The N-terminal region containing the 6 extracellular cadherin domains, unique to each protocadherin alpha, is encoded by one of the large exons found in tandem array within the gene cluster. The C-terminal region, identical to all protocadherins alpha, is encoded by 3 shared exons. http://togogenome.org/gene/10090:Nrap ^@ http://purl.uniprot.org/uniprot/Q80XB4 ^@ Developmental Stage|||Function|||Subunit|||Tissue Specificity ^@ Expressed in cardiac and skeletal muscle. Not detected in kidney, spleen, liver, brain, lung, stomach or uterus.|||Expression significantly increased from 10.5 dpc to 16.5 dpc, and subsequently remained constant until 21 days after birth. In 9.5 dpc to 10.5 dpc embryonic heart, expression is primarily associated with developing premyofibril structures containing alpha-actinin.|||Interacts with actin, alpha-actinin, KLHL41, TLN1 and VCL. Interacts with CSRP3.|||May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. http://togogenome.org/gene/10090:Nbn ^@ http://purl.uniprot.org/uniprot/Q9R207 ^@ Developmental Stage|||Domain|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A low level of expression is observed in all tissues. Highly specific expression was observed in organs with physiologic DNA double strand breakage (DSB), such as testis, thymus and spleen. Enhanced expression is also found at sites of high proliferative activity. These are the subventricular layer of the telencephalon and the diencephalon, the liver, lung, kidney and gut, as well as striated and smooth muscle cells in various organs.|||Chromosome|||Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints. The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability. Forms a complex with RBBP8 to link DNA double-strand break sensing to resection. Enhances AKT1 phosphorylation possibly by association with the mTORC2 complex (By similarity).|||Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN (By similarity). As part of the MRN complex, interacts with MCM9; the interaction recruits the complex to DNA repair sites (By similarity). Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN (By similarity). Interacts with histone H2AX this requires phosphorylation of H2AX on 'Ser-139' (By similarity). Interacts with HJURP, INTS3, KPNA2 and TERF2 (By similarity). Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection (By similarity). Interacts with SP100; recruits NBN to PML bodies (PubMed:12470659). Interacts with ATF2 (By similarity). Interacts with MTOR, MAPKAP1 isoform 2 and RICTOR; indicative for an association with the mTORC2 complex (By similarity). Interacts with MRNIP (By similarity). Interacts with UFL1; promoting UFL1 recruitment to double-strand breaks following DNA damage (By similarity). Interacts with CYREN (via XLF motif) (PubMed:30017584).|||High expression in the liver, heart and testis. Low expression in all other tissues analyzed. In the cerebellum the postmitotic Purkinje cells are marked specifically.|||Nucleus|||PML body|||Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.|||The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex.|||The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response.|||The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage.|||telomere http://togogenome.org/gene/10090:Cldn34b4 ^@ http://purl.uniprot.org/uniprot/Q3V0X2 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the claudin family.|||Cell membrane|||Membrane|||tight junction http://togogenome.org/gene/10090:Ccdc153 ^@ http://purl.uniprot.org/uniprot/P0C7Q1 ^@ Similarity ^@ Belongs to the UPF0610 family. http://togogenome.org/gene/10090:Cd24a ^@ http://purl.uniprot.org/uniprot/P24807 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the CD24 family.|||Cd22/Siglec10 double-deficient mice develop autoimmune disease, which is not observed in single-deficient mice.|||Cell membrane|||In lymphoid, myeloid, and erythroid cells.|||Interacts with SIGLEC10; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response.|||May have a pivotal role in cell differentiation of different cell types. May have a specific role in early thymocyte development. Signaling could be triggered by the binding of a lectin-like ligand to the CD24 carbohydrates, and transduced by the release of second messengers derived from the GPI-anchor. Modulates B-cell activation responses (By similarity). In association with SIGLEC10 may be involved in the selective suppression of the immune response to danger-associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90 (PubMed:19264983). Plays a role in the control of autoimmunity (PubMed:20200274).|||The identity of the N- and O-linked polysaccharides is not reported in PubMed:1530634. The O-linked polysaccharides on Ser-30, Ser-41, Ser-43, and Thr-51 are probably the mucin type linked to GalNAc. http://togogenome.org/gene/10090:D1Pas1 ^@ http://purl.uniprot.org/uniprot/B9EIA2|||http://purl.uniprot.org/uniprot/P16381 ^@ Developmental Stage|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the DEAD box helicase family.|||Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.|||High levels of PL10 during the meiotic and haploid stages of spermatogenesis.|||Putative ATP-dependent RNA helicase. Possible role in a key step of the spermatogenic process.|||Testis. http://togogenome.org/gene/10090:Ppp1r11 ^@ http://purl.uniprot.org/uniprot/A5A4Y9|||http://purl.uniprot.org/uniprot/Q8K1L5 ^@ Function|||PTM|||Subunit|||Tissue Specificity ^@ Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 at 'Lys-754' leading to its degradation by the proteasome. Plays a role in regulating inflammatory cytokine release and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2 (PubMed:27805901). Inhibitor of protein phosphatase 1 (By similarity).|||Auto-ubiquitinated.|||Expressed in testis with high level during spermatogenesis.|||Interacts with TLR2 and UBE2D2. http://togogenome.org/gene/10090:Efcab7 ^@ http://purl.uniprot.org/uniprot/Q8VDY4 ^@ Function|||Subcellular Location Annotation|||Subunit ^@ Component of the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE (PubMed:24582806). Interacts (via EF-hand 1 and 2) with IQCE (via N-terminus); this interaction anchors the EVC-EVC2 complex in a signaling microdomain at the base of cilia and stimulates the Hedgehog (Hh) pathway (PubMed:24582806). Interacts with EVC2 (via N-terminal end) (PubMed:24582806). Interacts with EVC (PubMed:24582806).|||Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling (PubMed:24582806). Required for the localization of the EVC2:EVC subcomplex at the base of primary cilia (PubMed:24582806).|||cilium membrane http://togogenome.org/gene/10090:Kcnmb4 ^@ http://purl.uniprot.org/uniprot/Q9JIN6 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB4 subfamily.|||Interacts with KCNMA1 tetramer (PubMed:10804197). There are probably 4 molecules of KCMNB4 per KCNMA1 tetramer (PubMed:10804197). Interacts with FMR1 (via N-terminus) (PubMed:25561520).|||Membrane|||N-glycosylated. A highly glycosylated form is promoted by KCNMA1. Glycosylation, which is not required for the interaction with KCNMA1 and subcellular location, increases protection against charybdotoxin (By similarity).|||Phosphorylated. Phosphorylation modulates its effect on KCNMA1 activation kinetics (By similarity).|||Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Decreases the gating kinetics and calcium sensitivity of the KCNMA1 channel, but with fast deactivation kinetics. May decrease KCNMA1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. Makes KCNMA1 channel resistant to 100 nM charybdotoxin (CTX) toxin concentrations (By similarity).|||Resistance to charybdotoxin (CTX) toxin is mediated by the extracellular domain. http://togogenome.org/gene/10090:Ago4 ^@ http://purl.uniprot.org/uniprot/Q8CJF8 ^@ Function|||PTM|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the argonaute family. Ago subfamily.|||Interacts with EIF4B, IMP8, PRMT5, TNRC6A and TNRC6B. Interacts with ZFP36.|||Intron retention.|||P-body|||Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs.|||Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO4 when it is engaged with a TDMD target. http://togogenome.org/gene/10090:Ttc39b ^@ http://purl.uniprot.org/uniprot/Q8BYY4 ^@ Disruption Phenotype|||Function|||Similarity|||Tissue Specificity ^@ Belongs to the TTC39 family.|||Chow-fed deficient mice display increased HDL-cholesterol level, accompanied by increased ABCA1 and MYLIP expression, increased oxysterols receptors LXR (NR1H3 and NR1H2) protein level without change in NR1H2/3 mRNA levels. Many NR1H2/3 targets are up-regulated, including ABCG5/8, SCD1, ELOVL5, INSIG2 and LPCAT3. Deficiency of TTC39B reduced processing of SREBP1 a pivotal regulator of lipogenesis. When fed with a high-fat/high-cholesterol/bile-salt diet during 20 weeks, used as a model of steatohepatitis resembling human non-alcoholic steatohepatitis, mice show increased HDL cholesterol and APOA1 levels, reduced VLDL (very low density lipoprotein), and reduced mortality compared with wild-type. The livers of deficient mice shown diminished hepatic triglyceride and cholesteryl ester accumulation, fewer inflammatory foci consisting of neutrophils and lymphocytes, less hepatocellular ballooning degeneration and less hepatocyte proliferation compared to control. Knockout mice lacking both TTC39B and LDLR, fed a Western diet for 20 weeks, exhibit a reduction in LDL-cholesterol, but plasma triglyceride levels are not different. Atherosclerotic lesion area of the aorta are reduced compared to LDLR single knockout mice.|||High expression in lung and spleen. Low lower expression in liver and small intestine. Weak expression in heart, brain, kidney, adipose, and adrenal gland.|||Regulates high density lipoprotein (HDL) cholesterol metabolism by promoting the ubiquitination and degradation of the oxysterols receptors LXR (NR1H2 and NR1H3). http://togogenome.org/gene/10090:Ahrr ^@ http://purl.uniprot.org/uniprot/Q3U1U7 ^@ Function|||Induction|||Subcellular Location Annotation|||Subunit ^@ By 3MC. Up-regulated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and beta-naphthoflavone in pituitary.|||Cytoplasm|||Interacts with ARNT, ANKRA2, HDAC4 and HDAC5. Interacts with ARNT; forms a heterodimer with ARNT (By similarity).|||Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site.|||Nucleus http://togogenome.org/gene/10090:Zp3r ^@ http://purl.uniprot.org/uniprot/G3X970|||http://purl.uniprot.org/uniprot/Q0VET1 ^@ Caution ^@ Lacks conserved residue(s) required for the propagation of feature annotation. http://togogenome.org/gene/10090:Asb2 ^@ http://purl.uniprot.org/uniprot/Q8K0L0 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Barely detectable in bone marrow cells but levels progressively increase as cells differentiate into immature dendritic cells and are down-regulated after dendritic cell maturation (PubMed:23632887). Highly expressed in the developing heart at 9.5 dpc when isoform 1 levels are very low (PubMed:29374072). Levels increase up to 11.5 dpc and fall in the adult heart (PubMed:29374072).|||Belongs to the ankyrin SOCS box (ASB) family.|||Both the N-terminus and ANK repeats 1 to 10 are necessary for interaction with filamins.|||Component of a probable ECS E3 ubiquitin-protein ligase complex which contains CUL5, either RBX1 or RNF7/RBX2, Elongin BC complex (ELOB and ELOC) and ASB2. Interacts with SKP2. Through its interaction with SKP2, likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex. Interacts with JAK2; the interaction targets JAK2 for Notch-mediated proteasomal degradation. Interacts with TCF3/E2A; the interaction is mediated by SKP2 and targets TCF3 for Notch-mediated proteasomal degradation.|||Conditional knockout in hematopoietic stem and progenitor cells results in increased protein levels of Flna and Flnb in immature dendritic cells (PubMed:23632887). Conditional knockout in hematopoietic cells reduces tumor development in a mouse model of colitis-associated tumorigenesis with reduced numbers of T helper type 2 (Th2) cells and regulatory T (Treg) cells and increased numbers of type 1 helper T (Th1) cells and T helper 17 (Th17) cells in the colonic mucosa of tumor-bearing mice (PubMed:31175139).|||Embryonic lethality with death occurring in utero around 9.5 dpc (PubMed:29374072). Embryos display defects in vascular development and hematopoiesis and increased protein levels of Flna in the heart (PubMed:29374072). Conditional knockout in the whole heart and in the first heart field results in pericardial edema and embryonic lethality (PubMed:32179481). Conditional knockout in the embryonic heart results in impaired heart looping, abnormal expression of Flna expression which is expanded to include the myocardial layer and increased expression of Smad2 (PubMed:32179481).|||Expressed in immature dendritic cells and in primary dendritic cells derived from the spleen (PubMed:23632887). Highly expressed in adult bone marrow with negligible levels in adult skeletal muscle (PubMed:29374072). Expressed at higher levels in T helper type 2 (Th2) cells than in regulatory T (Treg) cells, type 1 helper T (Th1) cells and T helper 17 (Th17) cells (PubMed:31175139).|||Highest expression in muscle, heart and spleen (PubMed:11111040). Highly expressed in cells of the first and second heart fields in the developing embryonic heart (PubMed:32179481). At 9.5 dpc, robust expression predominantly in the left and right ventricles (RV) and to a lower extent in inflow and outflow tracts (PubMed:32179481). At 10.5 and 11.5 dpc, expression is restricted to the myocardium with no expression observed in the endocardium (PubMed:32179481).|||Interacts with DES.|||Involved in myogenic differentiation and targets filamin FLNB for proteasomal degradation but not filamin FLNA (PubMed:26343497). Also targets DES for proteasomal degradation (PubMed:26343497). Acts as a negative regulator of skeletal muscle mass (PubMed:27182554).|||Monoubiquitinated.|||Not expressed in immature dendritic cells (PubMed:23632887). Highly expressed in adult skeletal muscle with very low levels in adult bone marrow (PubMed:29374072).|||Not monoubiquitinated.|||Phosphorylation at Ser-371 is required for association with FLNA and subsequent FLNA degradation.|||Repressed by FST in 6-month-old mice but no effect is seen in 24-month-old mice (PubMed:27182554). Expression is increased 4-fold 3 days after denervation, becomes suppressed by approximately 75% 7 days after denervation, and eventually resolves to baseline by 28 days after denervation (PubMed:27182554).|||Substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Mediates Notch-induced ubiquitination and degradation of substrates including TCF3/E2A and JAK2 (By similarity). Required during embryonic heart development for complete heart looping (PubMed:32179481). Required for cardiomyocyte differentiation (By similarity).|||Targets filamins FLNA and FLNB for proteasomal degradation (PubMed:23632887). This leads to enhanced adhesion of hematopoietic cells to fibronectin (By similarity). Required for FLNA degradation in immature cardiomyocytes which is necessary for actin cytoskeleton remodeling, leading to proper organization of myofibrils and function of mature cardiomyocytes (PubMed:29374072). Required for degradation of FLNA and FLNB in immature dendritic cells (DC) which enhances immature DC migration by promoting DC podosome formation and DC-mediated degradation of the extracellular matrix (PubMed:23632887). Does not promote proteasomal degradation of tyrosine-protein kinases JAK1 or JAK2 in hematopoietic cells (By similarity).|||The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes.|||The UIM domain is required for monoubiquitination.|||Very low levels found in the developing heart at 9.5 dpc when isoform 2 is the predominant isoform (PubMed:29374072, PubMed:32179481). Expression increases from 11.5 dpc and is the predominant isoform in adult heart (PubMed:29374072, PubMed:32179481).|||Z line|||stress fiber http://togogenome.org/gene/10090:Kdm2a ^@ http://purl.uniprot.org/uniprot/P59997 ^@ Cofactor|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the JHDM1 histone demethylase family.|||Binds 1 Fe(2+) ion per subunit.|||Chromosome|||Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:32584788). Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis (By similarity). Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-BMAL1 heterodimer and RORA in a catalytically-independent manner (By similarity).|||Mono-ADP-ribosylated at Arg-1019 in response to DNA damage, leading to displacement from chromatin, resulting in increased dimethylation of histone H3 at 'Lys-36'.|||Part of a SCF (SKP1-cullin-F-box) protein ligase complex. Interacts with CBX5/HP1A; the interaction promotes CBX5 localization to chromatin (By similarity). The SKP1-KDM2A complex interacts with UBB (By similarity).|||The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated (By similarity). It is essential for its ability to repress the transcriptional activator activity of CLOCK-BMAL1 heterodimer (By similarity).|||The F-box domain mediates interaction with UBB.|||The JmjC domain mediates demethylation activity and is required for satellite silencing.|||nucleoplasm http://togogenome.org/gene/10090:Gne ^@ http://purl.uniprot.org/uniprot/Q91WG8 ^@ Activity Regulation|||Developmental Stage|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Allosterically regulated; feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine; the hexamer is fully active for both enzyme activities (By similarity). Up-regulated after PKC-dependent phosphorylation.|||Cytoplasm|||Homodimer and homohexamer.|||In the C-terminal section; belongs to the ROK (NagC/XylR) family.|||In the N-terminal section; belongs to the UDP-N-acetylglucosamine 2-epimerase family.|||In the embryo, expressed at day 7 dpc, 11 dpc and 15 dpc.|||Phosphorylated by PKC.|||Regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. Required for normal sialylation in hematopoietic cells (By similarity). Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. Plays an essential role in early development.|||Widely expressed. Highest expression in liver. Also found at high levels in lung, brain and kidney. http://togogenome.org/gene/10090:Tex56 ^@ http://purl.uniprot.org/uniprot/Q497N7 ^@ Disruption Phenotype|||Tissue Specificity ^@ Deficient mice are viable and have normal fertility.|||Expressed predominantly in the testis. http://togogenome.org/gene/10090:Aif1 ^@ http://purl.uniprot.org/uniprot/O70200|||http://purl.uniprot.org/uniprot/Q4FJL9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Abundantly expressed in the testis, moderately in the spleen and lymph nodes and at low levels in the liver and thymus. Detected in macrophages.|||Actin-binding protein that enhances membrane ruffling and RAC activation. Enhances the actin-bundling activity of LCP1. Binds calcium. Plays a role in RAC signaling and in phagocytosis. May play a role in macrophage activation and function. Promotes the proliferation of vascular smooth muscle cells and of T-lymphocytes. Enhances lymphocyte migration. Plays a role in vascular inflammation.|||Homodimer (Potential). Monomer. Interacts with LCP1.|||Phosphorylated on serine residues.|||cytoskeleton|||phagocytic cup|||ruffle membrane http://togogenome.org/gene/10090:Lpin2 ^@ http://purl.uniprot.org/uniprot/E9PWN0|||http://purl.uniprot.org/uniprot/Q99PI5 ^@ Activity Regulation|||Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the reticulum endoplasmic membrane (PubMed:17158099). Plays important roles in controlling the metabolism of fatty acids at different levels. Acts also as a nuclear transcriptional coactivator for PPARGC1A to modulate lipid metabolism.|||Belongs to the lipin family.|||By fasting in hepatocytes. Up-regulated in fld/fld (defect in LPIN1) mice. Up-regulated at protein level but not at transcript level in ob/ob and db/db mice, two obese mice models.|||Contains 1 Asp-Xaa-Asp-Xaa-Thr (DXDXT) motif, a catalytic motif known to be essential for phosphatidate phosphatase activity.|||Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, a motif known to be a transcriptional binding motif.|||Endoplasmic reticulum membrane|||Expressed at high level in liver and to some extend in lung, kidney, placenta, spleen, thymus, lymph node, prostate, testes, small intestine, and colon. Expressed also in circulating red blood cells and site of lymphopoiesis.|||Inhibited by N-ethylmaleimide.|||Nucleus|||cytosol http://togogenome.org/gene/10090:Crcp ^@ http://purl.uniprot.org/uniprot/O35427 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Accessory protein for the calcitonin gene-related peptide (CGRP) receptor. It modulates CGRP responsiveness in a variety of tissues.|||Belongs to the eukaryotic RPC9 RNA polymerase subunit family.|||Cell membrane|||Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. Interacts with POLR3H/RPC8. POLR3H/RPC8 and CRCP/RPC9 probably form a Pol III subcomplex (By similarity).|||DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts induce type I interferon and NF- Kappa-B through the RIG-I pathway (By similarity).|||Nucleus|||Ubiquitous. Most prevalent in testis. http://togogenome.org/gene/10090:Scgb2b17 ^@ http://purl.uniprot.org/uniprot/A0A089N3E7|||http://purl.uniprot.org/uniprot/S4R2V3 ^@ Similarity ^@ Belongs to the secretoglobin family. http://togogenome.org/gene/10090:Obox1 ^@ http://purl.uniprot.org/uniprot/Q9D350 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Or51f5 ^@ http://purl.uniprot.org/uniprot/Q8VGZ6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pigk ^@ http://purl.uniprot.org/uniprot/Q8BL63|||http://purl.uniprot.org/uniprot/Q9CXY9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C13 family.|||Component of the GPI transamidase complex, necessary for transfer of GPI to proteins (By similarity). Mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI. During this transamidation reaction, the GPI transamidase forms a carbonyl intermediate with the substrate protein (By similarity).|||Endoplasmic reticulum membrane|||Forms a complex with PIGT, PIGS, PIGU and GAA1.|||The disulfide bond between PIGK/GPI8 and PIGT is important for normal enzyme activity. http://togogenome.org/gene/10090:Pomt2 ^@ http://purl.uniprot.org/uniprot/Q8BGQ4 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glycosyltransferase 39 family.|||Endoplasmic reticulum membrane|||May be produced by use of an alternative promoter.|||N-glycosylated.|||Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. Coexpression of both POMT1 and POMT2 is necessary for enzyme activity, expression of either POMT1 or POMT2 alone is insufficient. Essentially dedicated to O-mannosylation of alpha-DAG1 and few other proteins but not of cadherins and protocaherins.|||Ubiquitous. Highly expressed in the acrosome of cap phase spermatids, in spermatocytes and liver. Isoform 1 seems to be testis-specific. http://togogenome.org/gene/10090:Brf2 ^@ http://purl.uniprot.org/uniprot/Q3UAW9 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TFIIB family.|||Component of TFIIIB complexes. The TFIIIB complex has two activities, alpha and beta. The TFIIIB-alpha activity complex is composed of TBP, BDP1, and a complex containing both BRF2 and at least four stably associated proteins; this complex inhibits the transcription by pol III via its phosphorylation by CK2; YY1 facilitates the TFIIIB-alpha complex formation. Interacts with TBP; this interaction promotes recruitment of BRF2 to TATA box-containing promoters. Interacts with TBP and the BURE sequence (GC-rich sequence downstream from the TATA box) to form a strong ternary complex which is joined by BDP1; this ternary complex stimulates pol III transcription. Forms a trimeric complex composed of TBP, BRF2 and mini-SNAPc complex (SNAP43, SNAP50, and the N-terminal third of SNAP190) on the promoter. Assembly of the TBP-BRF2 complex is stimulated by SNAP190. Interacts with MAF1 and SNAPC4.|||General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites. Contributes to the regulation of gene expression; functions as activator in the absence of oxidative stress. Down-regulates expression of target genes in response to oxidative stress. Overexpression protects cells against apoptosis in response to oxidative stress.|||In response to oxidative stress, Cys-362 is reversibly oxidized to cysteine sulfenic acid. Oxidation of Cys-362 impairs formation of a ternary complex with TBP and DNA and down-regulates expression of target genes in response to oxidative stress.|||Nucleus http://togogenome.org/gene/10090:Flot2 ^@ http://purl.uniprot.org/uniprot/Q3UEG9|||http://purl.uniprot.org/uniprot/Q60634 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the band 7/mec-2 family. Flotillin subfamily.|||Cell membrane|||Endosome|||Expressed in many tissues, including suprabasal epidermis, hair follicles, heart, lung, thymus, spleen, liver, kidney and brain. Not expressed in skeletal muscle.|||Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS (By similarity).|||Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS.|||May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles.|||May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. May be involved in epidermal cell adhesion and epidermal structure and function.|||Membrane|||Membrane raft|||ZDHHC5-catalyzed palmitoylation may be required for the formation of higher-order complexes and for neurite outgrowth in cultured neural stem cells.|||caveola http://togogenome.org/gene/10090:Or2h15 ^@ http://purl.uniprot.org/uniprot/Q7TRI8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Pcdhga8 ^@ http://purl.uniprot.org/uniprot/Q91XY0 ^@ Function|||Subcellular Location Annotation ^@ Cell membrane|||Membrane|||Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain. http://togogenome.org/gene/10090:Cdc42bpg ^@ http://purl.uniprot.org/uniprot/Q80UW5 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.|||Cytoplasm|||Homodimer and homotetramer via the coiled coil regions. Interacts tightly with GTP-bound but not GDP-bound CDC42 (By similarity).|||Maintained in an inactive, closed conformation by an interaction between the kinase domain and the negative autoregulatory C-terminal coiled-coil region. Agonist binding to the phorbol ester binding site disrupts this, releasing the kinase domain to allow N-terminus-mediated dimerization and kinase activation by transautophosphorylation (By similarity).|||May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation (By similarity). http://togogenome.org/gene/10090:Dgat2 ^@ http://purl.uniprot.org/uniprot/Q9DCV3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the diacylglycerol acyltransferase family.|||Endoplasmic reticulum membrane|||Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage of intracellular triglycerides. Probably plays a central role in cytosolic lipid accumulation. In liver, is primarily responsible for incorporating endogenously synthesized fatty acids into triglycerides. Functions also as an acyl-CoA retinol acyltransferase (ARAT) (By similarity). Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (By similarity).|||Forms multimeric complexes consisting of several DGAT2 subunits (PubMed:21680734). Interacts with SLC27A1 and this interaction is enhanced in the presence of ZFYVE1 (By similarity).|||In white adipose tissue, it is regulated by leptin. By insulin. Up-regulated in diabetic mice. Down-regulated upon fasting and replenished upon refeeding in adipose tissue and liver. Down-regulation in obese animals can reduce hepatic lipogenesis and hepatic steatosis as well as attenuate hyperlipidemia, thereby leading to an improvement in metabolic syndrome.|||Inhibited by niacin.|||Lipid droplet|||Mice are lipopenic and die soon after birth, apparently from profound reductions in substrates for energy metabolism and from impaired permeability barrier function in the skin.|||Predominantly expressed in liver. Also expressed in testis.|||perinuclear region http://togogenome.org/gene/10090:Or2b4 ^@ http://purl.uniprot.org/uniprot/Q8VGW6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmem40 ^@ http://purl.uniprot.org/uniprot/Q4FJU9 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Tmem26 ^@ http://purl.uniprot.org/uniprot/Q3UP23 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Mocos ^@ http://purl.uniprot.org/uniprot/Q14CH1 ^@ Function|||Similarity ^@ Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. MOCOS subfamily.|||Sulfurates the molybdenum cofactor. Sulfation of molybdenum is essential for xanthine dehydrogenase (XDH) and aldehyde oxidase (ADO) enzymes in which molybdenum cofactor is liganded by 1 oxygen and 1 sulfur atom in active form. http://togogenome.org/gene/10090:Or7e175 ^@ http://purl.uniprot.org/uniprot/A0A2I3BRV7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Srrm2 ^@ http://purl.uniprot.org/uniprot/Q8BTI8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CWC21 family.|||Component of pre-catalytic, catalytic and post-catalytic spliceosome complexes. Found in a pre-mRNA splicing complex with SFRS4, SFRS5, SNRP70, SNRPA1, SRRM1 and SRRM2. Component of the minor spliceosome, which splices U12-type introns (By similarity). Interacts with DHX8. Interacts with CACTIN.|||Nucleus|||Nucleus speckle|||Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (By similarity). http://togogenome.org/gene/10090:Jade3 ^@ http://purl.uniprot.org/uniprot/Q6IE82 ^@ Function|||Similarity|||Subunit ^@ Belongs to the JADE family.|||Component of the HBO1 complex composed at least of ING4 or ING5, MYST2/HBO1, MEAF6, and one of JADE1, JADE2 and JADE3.|||Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. http://togogenome.org/gene/10090:Vmn2r117 ^@ http://purl.uniprot.org/uniprot/K7N6V1 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Gtf2a1 ^@ http://purl.uniprot.org/uniprot/Q0VGZ0|||http://purl.uniprot.org/uniprot/Q149E9|||http://purl.uniprot.org/uniprot/Q99PM3 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TFIIA subunit 1 family.|||Expressed in pachytene spermatocytes and spermatids.|||Nucleus|||TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation. TFIIA in a complex with TBP mediates transcriptional activity (By similarity).|||TFIIA is a heterodimer of a unprocessed large subunit 1 and a small subunit gamma. It was originally believed to be a heterotrimer of an alpha, a beta and a gamma subunit. TFIIA forms a complex with TBP (By similarity).|||The alpha and beta subunits are postranslationally produced from the precursor form by TASP1. The cleavage promotes proteasomal degradation (By similarity).|||Up-regulated during germ cell differentiation in testis. http://togogenome.org/gene/10090:Elof1 ^@ http://purl.uniprot.org/uniprot/P60003|||http://purl.uniprot.org/uniprot/Q545S6 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the ELOF1 family.|||Nucleus|||Transcription elongation factor implicated in the maintenance of proper chromatin structure in actively transcribed regions. http://togogenome.org/gene/10090:Capn13 ^@ http://purl.uniprot.org/uniprot/Q3UW68 ^@ Caution|||Function|||Similarity ^@ Belongs to the peptidase C2 family.|||It is unlikely that this protein binds calcium as none of the 2 EF-hand domains seem to contain a canonical calcium-binding site.|||Probable non-lysosomal thiol-protease. http://togogenome.org/gene/10090:Sbk1 ^@ http://purl.uniprot.org/uniprot/Q8QZX0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.|||Cytoplasm|||May be involved in signal-transduction pathways related to the control of brain development. http://togogenome.org/gene/10090:Sys1 ^@ http://purl.uniprot.org/uniprot/Q78S06 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the SYS1 family.|||Golgi apparatus membrane|||Interacts with ARFRP1.|||Involved in protein trafficking. May serve as a receptor for ARFRP1 (By similarity). http://togogenome.org/gene/10090:Gpam ^@ http://purl.uniprot.org/uniprot/Q61586 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the GPAT/DAPAT family.|||Esterifies acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate, an essential step in glycerolipids biosynthesis such as triglycerides, phosphatidic acids and lysophosphatidic acids.|||Highest levels in liver, intermediate levels in muscle and kidney, and lowest levels in lung and brain.|||Mitochondrion outer membrane|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate. http://togogenome.org/gene/10090:Slc34a2 ^@ http://purl.uniprot.org/uniprot/Q9DBP0 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Apical cell membrane|||Belongs to the SLC34A transporter family.|||Highly abundant in the ileum of small intestine, whereas it is almost absent in the duodenum and in the jejunum.|||Involved in actively transporting phosphate into cells via Na(+) cotransport.|||Up-regulated in the entire small intestine by low-phosphate diet. Up-regulated by metabolic acidosis. http://togogenome.org/gene/10090:Rab3gap1 ^@ http://purl.uniprot.org/uniprot/Q80UJ7 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Rab3-GAP catalytic subunit family.|||Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of Rab3gap1 and Rab3gap2, which has GTPase-activating protein (GAP) activity towards various Rab3 subfamily members (RAB3A, RAB3B, RAB3C and RAB3D), RAB5A and RAB43, and guanine nucleotide exchange factor (GEF) activity towards RAB18 (By similarity). As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP (By similarity). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones (By similarity). The Rab3GAP complex, acts as a GEF for RAB18 by promoting the conversion of inactive RAB18-GDP to the active form RAB18-GTP (By similarity). Required for recruiting and activating RAB18 at the endoplasmic reticulum (ER) membrane where it maintains proper ER structure (By similarity). Required for normal eye and brain development (By similarity). May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters (By similarity).|||Cytoplasm|||Endoplasmic reticulum|||From 10 dpc to 12 dpc, it is weakly expressed throughout the embryo. At 14.5 dpc, it is predominantly expressed in a number of organ systems, including the central and peripheral nervous systems.|||In the eye, it is highly expressed within the lens, particularly in the anterior lens epithelium and in a ring corresponding to the equatorial region where anterior cells are differentiating into lens fibers. Also highly expressed in the retina.|||The Rab3 GTPase-activating complex is a heterodimer composed of Rab3gap1 and Rab3gap2 (By similarity). The Rab3 GTPase-activating complex interacts with DMXL2 (By similarity). Interacts with LMAN1 (By similarity). http://togogenome.org/gene/10090:Pabpc4 ^@ http://purl.uniprot.org/uniprot/A3KFU5|||http://purl.uniprot.org/uniprot/A3KFU8|||http://purl.uniprot.org/uniprot/Q6PHQ9|||http://purl.uniprot.org/uniprot/Q91YZ8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the polyadenylate-binding protein type-1 family.|||Binds the poly(A) tail of mRNA.|||Cytoplasm http://togogenome.org/gene/10090:Eef1b2 ^@ http://purl.uniprot.org/uniprot/O70251 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the EF-1-beta/EF-1-delta family.|||EF-1 is composed of 4 subunits: alpha, beta, delta, and gamma.|||EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP.|||Phosphorylation affects the GDP/GTP exchange rate. http://togogenome.org/gene/10090:Ccdc85a ^@ http://purl.uniprot.org/uniprot/E0CX32|||http://purl.uniprot.org/uniprot/Q5SP85 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC85 family.|||May interact with ARVCF; CTNND1; CTNND2 and PKP4.|||May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family.|||Probable cloning artifact. May result from internal priming due to genomic poly-A tracts.|||adherens junction http://togogenome.org/gene/10090:Pan3 ^@ http://purl.uniprot.org/uniprot/Q640Q5 ^@ Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily. PAN3 family.|||Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs.|||Cytoplasm|||Decreases PAN2-mediated deadenylation, possibly by preventing progression into the second CCR4-NOT mediated stage of biphasic deadenylation. Has a significant effect on mRNA stability, generally stabilizing a subset of the transcriptome. Stabilizes mRNAs degraded by the AU-rich element (ARE)-mediated mRNA decay pathway but promotes degradation of mRNAs by the microRNA-mediated pathway. Its activity influences mRNP remodeling, specifically reducing formation of a subset of P-bodies containing GW220, an isoform of TNRC6A.|||Enhances PAN2 deadenylase activity and has an extensive effect on mRNA stability, generally enhancing mRNA decay across the transcriptome by multiple pathways, including the AU-rich element (ARE)-mediated pathway, microRNA-mediated pathway and the nonsense-mediated pathway (NMD). Its activity is required for efficient P-body formation. May be involved in regulating mRNAs of genes involved in cell cycle progression and cell proliferation.|||Homodimer. Forms a heterotrimer with a catalytic subunit PAN2 to form the poly(A)-nuclease (PAN) deadenylation complex. Interacts (via PAM-2 motif) with poly(A)-binding protein PABPC1 (via PABC domain), conferring substrate specificity of the enzyme complex. Interacts with the GW182 family proteins TNRC6A, TNRC6B and TNRC6C (By similarity). Interacts with YTHDF3 (PubMed:32905781).|||Interacts with PAN2. Interacts (via N-terminus) with PABPC1 at higher efficiency than isoform 1.|||Interacts with PAN2. Interacts (via N-terminus) with PABPC1 at lower efficiency than isoform 3.|||Intron retention.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||P-body|||Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenylation-dependent mRNA decapping and subsequent 5'-3' exonucleolytic degradation by XRN1. PAN3 acts as a regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with RNA and PABP, and to miRNA targets via its interaction with GW182 family proteins.|||Several sequencing errors.|||The N-terminal zinc finger binds to poly(A) RNA.|||The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for PAN2. http://togogenome.org/gene/10090:Kifap3 ^@ http://purl.uniprot.org/uniprot/P70188 ^@ Function|||PTM|||Subunit ^@ Interacts with SMC3 subunit of the cohesin complex (By similarity). Heterotrimer of KIFAP3, KIF3A and KIF3B. Interacts with RAP1GDS1/SMG GDS.|||Involved in tethering the chromosomes to the spindle pole and in chromosome movement. Binds to the tail domain of the KIF3A/KIF3B heterodimer to form a heterotrimeric KIF3 complex and may regulate the membrane binding of this complex.|||Phosphorylated on tyrosine residues by SRC in vitro; this reduces the binding affinity of the protein for RAP1GDS1. http://togogenome.org/gene/10090:Or52r1c ^@ http://purl.uniprot.org/uniprot/Q8VGW0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Fam118b ^@ http://purl.uniprot.org/uniprot/Q8C569 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM118 family.|||Cajal body|||May play a role in Cajal bodies formation. http://togogenome.org/gene/10090:Nudcd1 ^@ http://purl.uniprot.org/uniprot/A0A2K6EDK3|||http://purl.uniprot.org/uniprot/Q6PIP5|||http://purl.uniprot.org/uniprot/Q8BJK0 ^@ Subcellular Location Annotation ^@ Cytoplasm|||Nucleus http://togogenome.org/gene/10090:Grin3b ^@ http://purl.uniprot.org/uniprot/Q91ZU9 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR3B/GRIN3B subfamily.|||Cell membrane|||Expressed in the facial nucleus and the ambiguus nucleus of the brainstem, pons, medulla, spinal cord and cerebellum.|||Forms heteromeric channel of a zeta subunit (GRIN1), a epsilon subunit (GRIN2A, GRIN2B, GRIN2C or GRIN2D) and a third subunit (GRIN3A or GRIN3B). Does not form functional homomeric channels. Found in a complex with GRIN1 and GRIN2A or GRIN2B.|||NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.|||Postsynaptic cell membrane http://togogenome.org/gene/10090:Prg2 ^@ http://purl.uniprot.org/uniprot/Q61878 ^@ Function|||PTM|||Subcellular Location Annotation ^@ Cytotoxin and helminthotoxin. MBP also induces non-cytolytic histamine release from basophils. It is involved in antiparasitic defense mechanisms and immune hypersensitivity reactions (By similarity).|||Nitrated.|||Secreted http://togogenome.org/gene/10090:G6pc ^@ http://purl.uniprot.org/uniprot/P35576 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the glucose-6-phosphatase family.|||Deficient mice display hypoglycaemia, growth retardation, hepatomegaly, kidney enlargement, hyperlipidaemia, and hyperuricaemia.|||Endoplasmic reticulum membrane|||Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. Forms with the glucose-6-phosphate transporter (SLC37A4/G6PT) the complex responsible for glucose production in the terminal step of glycogenolysis and gluconeogenesis. Hence, it is the key enzyme in homeostatic regulation of blood glucose levels.|||Liver and kidney. http://togogenome.org/gene/10090:Naip2 ^@ http://purl.uniprot.org/uniprot/Q9QUK4 ^@ Function|||Subunit ^@ Component of the NLRC4 inflammasome, at least composed of NLRC4, caspase-1 (CASP1) and some NAIP protein. Interacts with S.typhimurium (Salmonella) PrgJ and B.thailandensis BsaK.|||Sensor component of the NLRC4 inflammasome that specifically recognizes and binds type III secretion system (T3SS) rod proteins such as S.typhimurium (Salmonella) PrgJ and B.thailandensis BsaK from pathogenic bacteria. Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri. Prevents motor-neuron apoptosis induced by a variety of signals. http://togogenome.org/gene/10090:Dcaf1 ^@ http://purl.uniprot.org/uniprot/Q80TR8 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex. The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition. Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors. Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2. By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (PubMed:24357321).|||Belongs to the VPRBP/DCAF1 family.|||Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex. Interacts with DDB1; the interaction is direct. Also forms a ternary complex with DDA1 and DDB1. Interacts with NF2 (via FERM domain). Component of the EDVP complex, a E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1. Interacts with DYRK2; the interaction is direct. Interacts with RAG1; the interaction is direct. Interacts with LLGL1 and LLGL2. Interacts with histone H3. Interacts with ESR1 and LATS1; probably recruited by LATS1 to promote ESR1 ubiquitination and ubiquitin-mediated proteasomal degradation. Directly interacts with TET1, TET2 and TET3 (via C-terminus) (By similarity).|||Cytoplasm|||Early embryonic lethality. Conditional knockout in mouse embryonic fibroblasts results in severely defective progression through S phase and subsequent apoptosis (PubMed:18606781). Conditional knockout in B lineage-specific cells arrests B-cell development at the pro-B-to-pre-B cell transition: mice display modest reduction of D-J(H) rearrangement, while V(H)-DJ(H) and V(kappa)-J(kappa) rearrangements are severely impaired. D-J(H) coding joints show longer junctional nucleotide insertions and a higher mutation frequency in D and J segments than normal (PubMed:22157821).|||Expressed at high levels in germinal vesicle (GV) stage oocytes and at lower levels in MII-stage oocytes and zygotes (PubMed:24357321). Expression decreases from 4-cell stage to blastula (PubMed:24357321).|||Nucleus|||The DWD boxes are required for interaction with DDB1.|||The chromo domain with a restricted pocket directly recognizes monomethylated substrates.|||The protein kinase-like region mediates the threonine-protein kinase activity.|||Widely expressed (PubMed:11223251). Expressed in oocytes and zygotes (at protein level) (PubMed:24357321, PubMed:25557551). http://togogenome.org/gene/10090:Pkn2 ^@ http://purl.uniprot.org/uniprot/Q8BWW9 ^@ Activity Regulation|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Activated by limited proteolysis with trypsin. Proteolytically cleaved by caspase-3 during the induction of apoptotic cell death.|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Cell junction|||Cleavage furrow|||Cytoplasm|||Interacts (via the REM repeats) with RHOA (GTP-bound form preferentially) and interacts (via the REM repeats) with RAC1 (GTP-bound form preferentially); the interactions induce its autophosphorylation (PubMed:17403031, PubMed:20974804). Interacts with NCK1 (via SH3 domains) (PubMed:8910519). Interacts with RHOC. Interacts with NCK1 and NCK2 (By similarity). Interacts with CD44 (PubMed:17403031). Interacts (via C-terminal kinase domain) with PDPK1; the interaction stimulates PDPK1 kinase activity (By similarity). Interacts with MAP3K2; the interaction activates PRK2 kinase activity in a MAP3K2-independent kinase activity (PubMed:10818102). Interacts (via C-terminal domain) with AKT1; the interaction occurs with the C-terminal cleavage product of PRK2 in apoptotic cells. Interacts (via C-terminus) with PTPN13 (via PDZ 3 domain). Interacts with CDK10 (By similarity).|||Kinase activity is activated upon binding to GTP-bound Rho1/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during apoptosis. Activated by lipids, particularly cardiolipin and to a lesser extent by other acidic phospholipids and unsaturated fatty acids. Two specific sites, Thr-815 (activation loop of the kinase domain) and Thr-957 (turn motif), need to be phosphorylated for its full activation (By similarity).|||Membrane|||Midbody|||Nucleus|||PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (By similarity).|||Phosphorylated during mitosis (By similarity). Autophosphorylated. Phosphorylated. Phosphorylated by CDK10 (By similarity).|||The C1 domain does not bind the diacylglycerol (DAG).|||The N-terminal regioninterferes with the interaction between AKT1 and the C-terminal regionof PKN2.|||The apoptotic C-terminal cleavage product inhibits EGF-induced kinase activity of AKT1 phosphorylation at 'Thr-308' and 'Ser-473' sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ phosphorylations.|||Ubiquitous. Highly expressed in liver and lung Expressed in astrocytes (at protein level). Ubiquitous.|||cytoskeleton|||lamellipodium http://togogenome.org/gene/10090:Mafk ^@ http://purl.uniprot.org/uniprot/Q61827 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the bZIP family. Maf subfamily.|||Highly expressed in heart, skeletal muscle and placenta. Also expressed in erythroid cells.|||Homodimer or heterodimer (By similarity). It can form high affinity heterodimers with members of the CNC-bZIP family such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3 (PubMed:9240432).|||Nucleus|||Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves (By similarity). However, they act as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3, and recruiting them to specific DNA-binding sites (PubMed:9240432). Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor (By similarity). http://togogenome.org/gene/10090:Snx32 ^@ http://purl.uniprot.org/uniprot/Q80ZJ7 ^@ Function|||Similarity ^@ Belongs to the sorting nexin family.|||May be involved in several stages of intracellular trafficking. http://togogenome.org/gene/10090:Ppp1r7 ^@ http://purl.uniprot.org/uniprot/Q3UM45 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the SDS22 family.|||Interacts with PPP1CA, PPP1CB and PPP1CC/PPP1G.|||Nucleus|||Regulatory subunit of protein phosphatase 1.|||Widely expressed with high level in testis. Expression increases during puberty. Expressed in spermatids and probably also in spermatozoa. http://togogenome.org/gene/10090:Ift74 ^@ http://purl.uniprot.org/uniprot/Q8BKE9 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the IFT74 family.|||Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88 (PubMed:16775004, PubMed:23810713). Interacts with IFT81; the interaction is direct: within the IFT complex B, IFT74 and IFT81 mediate the transport of tubulin within the cilium. Interacts (via basic region) with beta-tubulin (via acidic region); interaction is direct. Interacts with ARL13B and IFT88. Interacts (via the IFT74/IFT81 heterodimer) with RABL2B (By similarity). Interacts with IFT57 and IFT70B (PubMed:23810713).|||Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds beta-tubulin via its basic region. Required for ciliogenesis (By similarity). Essential for flagellogenesis during spermatogenesis (PubMed:31004481).|||Cytoplasmic vesicle|||In testis, expression starts at day 12 and strongly increases on day 20 and thereafter, temporally correlating with the first wave of spermatogenesis.|||Predominantly expressed in testis, but also detected in other organs containing cilia-bearing cells, including lung, brain and kidney (at protein level).|||acrosome|||cilium|||flagellum http://togogenome.org/gene/10090:Cask ^@ http://purl.uniprot.org/uniprot/B9EJ23|||http://purl.uniprot.org/uniprot/O70589 ^@ Activity Regulation|||Cofactor|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the MAGUK family.|||CASK and LIN7 form a tripartite complex with CASKIN1 (By similarity). Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules (PubMed:10846156). Forms a heterotrimeric complex with DLG1 and LIN7B via their L27 domains (PubMed:22337881, PubMed:15863617). Identified in a complex with ACTN4, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Part of a complex containing CASK, TBR1 and TSPYL2 (PubMed:10749215, PubMed:15066269). Interacts with WHRN (By similarity). Interacts (via the PDZ, SH3 and guanylate kinase-like domains) with NRXN1 (via C-terminus) (PubMed:25385611). Interacts with CASKIN1, APBA1, LIN7(A/B/C), and L27 domain of DLG1 and isoform 2 of DLG4 (By similarity). Interacts with FCHSD2 (By similarity). Interacts with KIRREL3 (By similarity). Interacts with TBR1 (By similarity). Interacts with TSPYL2 (PubMed:15066269).|||Cell membrane|||Cytoplasm|||Differs from archetypal CaMK members in that the kinase domain exhibits a constitutively active conformation and the autoinhibitory region does not engage in direct contact with the ATP-binding cleft, although it still binds Ca(2+)/CAM.|||In the N-terminal section; belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.|||Multidomain scaffolding Mg(2+)-independent protein kinase that catalyzes the phosphotransfer from ATP to proteins such as NRXN1, and plays a role in synaptic transmembrane protein anchoring and ion channel trafficking (By similarity). Contributes to neural development and regulation of gene expression via interaction with the transcription factor TBR1. Binds to cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. May mediate a link between the extracellular matrix and the actin cytoskeleton via its interaction with syndecan and with the actin/spectrin-binding protein 4.1. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (PubMed:10846156).|||Nucleus|||The first L27 domain binds DLG1 and the second L27 domain probably binds LIN7.|||The protein kinase domain mediates the interaction with FCHSD2.|||Unlike other protein kinases, does not require a divalent cation such as magnesium for catalytic activity. http://togogenome.org/gene/10090:Aasdhppt ^@ http://purl.uniprot.org/uniprot/Q9CQF6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the P-Pant transferase superfamily. AcpS family.|||Binds 1 Mg(2+) ion.|||Catalyzes the post-translational modification of target proteins by phosphopantetheine. Can transfer the 4'-phosphopantetheine moiety from coenzyme A, regardless of whether the CoA is presented in the free thiol form or as an acetyl thioester, to a serine residue of a broad range of acceptors including the acyl carrier domain of FASN.|||Monomer.|||cytosol http://togogenome.org/gene/10090:Mgat4b ^@ http://purl.uniprot.org/uniprot/Q812F8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycosyltransferase 54 family.|||Glycosyltransferase that catalyzes the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary N-linked sugar chains. Prefers complex-type N-glycans over hybrid-types. Has lower affinities for donors or acceptors than MGAT4A, suggesting that, under physiological conditions, it is not the main contributor in N-glycan biosynthesis.|||Golgi apparatus membrane|||Interacts with SLC35A3.|||N-glycosylated. http://togogenome.org/gene/10090:Kars ^@ http://purl.uniprot.org/uniprot/Q3TIV6|||http://purl.uniprot.org/uniprot/Q8R2P8|||http://purl.uniprot.org/uniprot/Q99MN1 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the class-II aminoacyl-tRNA synthetase family.|||Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity.|||Cell membrane|||Cytoplasm|||Homodimer (By similarity). Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:14975237). Interacts with AIMP2 (via N-terminus) and MITF (PubMed:14975237). Interacts with TARSL2 (By similarity).|||It is likely that the same gene provides both this cytoplasmic isoform and an additional mitochondrial isoform.|||Nucleus|||Phosphorylated on a serine residue after mast cell stimulation with immunoglobulin E (IgE).|||Secreted|||Shares a bidirectional promoter with Terf2ip/Rap1.|||The N-terminal domain (1-65) is a functional tRNA-binding domain and is involved in the interaction with DARS, but has a repulsive role in the binding to EEF1A1. A central domain (208-259) is involved in homodimerization. The C-terminal domain (452-597) is not required for interaction with AIMP2 (By similarity).|||cytosol http://togogenome.org/gene/10090:Or10j2 ^@ http://purl.uniprot.org/uniprot/A0A140T8J6 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrgprx2 ^@ http://purl.uniprot.org/uniprot/Q3UFT2|||http://purl.uniprot.org/uniprot/Q3UG50 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family. Mas subfamily.|||Cell membrane|||In spite of its official gene name, this protein may not be the functional ortholog of human MRGPRX2.|||Membrane|||Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity). http://togogenome.org/gene/10090:Gpr68 ^@ http://purl.uniprot.org/uniprot/Q8BFQ3 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Expressed in the lung, testis, heart, brain, spleen, thymus, brown fat, small intestine, colon, peripheral blood leukocytes, macrophages, stomach, ovary and white fat but not in the liver, kidney, and skeletal muscle. Expression in the prostate is weak but detectable.|||Mice have reduced osteoclasts derived from bone marrow cells, a pH-dependent osteoclast survival effect is also detected. However, the overall bone structures of the mice are not affected. In addition melanoma cell tumorigenesis is significantly inhibited.|||Proton-sensing receptor involved in pH homeostasis. May represents an osteoblastic pH sensor regulating cell-mediated responses to acidosis in bone. Mediates its action by association with G proteins that stimulates inositol phosphate (IP) production or Ca(2+) mobilization. The receptor is almost silent at pH 7.8 but fully activated at pH 6.8. Also functions as a metastasis suppressor gene in prostate cancer. http://togogenome.org/gene/10090:Or51b6b ^@ http://purl.uniprot.org/uniprot/E9Q382 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Cldn8 ^@ http://purl.uniprot.org/uniprot/Q3UZK2|||http://purl.uniprot.org/uniprot/Q9Z260 ^@ Caution|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the claudin family.|||Cell membrane|||Conditional knockout mice lacking Cldn8 in the collecting duct of kidney show hypotension, hypokalemia, and metabolic alkalosis (PubMed:25831548).|||Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3 (PubMed:10601346). Interacts with CLDN4 (PubMed:20921420). Interacts with KLHL3 (PubMed:25831548).|||Expressed primarily in lung and kidney (PubMed:9892664). Present in both cortical and medullar collecting ducts (at protein level) (PubMed:20921420).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||Tight-junction protein required for paracellular chloride transport in the kidney (PubMed:20921420, PubMed:25831548). Mediates recruitment of CLDN4 to tight junction in the kidney (PubMed:20921420, PubMed:25831548). Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.|||Ubiquitinated by the BCR(KLHL3) E3 ubiquitin ligase complex in the kidney, leading to its degradation.|||tight junction http://togogenome.org/gene/10090:Xkr6 ^@ http://purl.uniprot.org/uniprot/E9Q6C8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the XK family.|||Cell membrane http://togogenome.org/gene/10090:Cst3 ^@ http://purl.uniprot.org/uniprot/P21460 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.|||Belongs to the cystatin family.|||Secreted http://togogenome.org/gene/10090:Ezhip ^@ http://purl.uniprot.org/uniprot/B1B0V2 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Highly expressed in ovary with lower expression in testis and very low levels in other tissues tested including prostate, brain, kidney, spleen and liver (PubMed:31451685). During spermatogenesis, expressed mainly in spermatogonia with very low expression in spermatocytes I and II (PubMed:31451685).|||Inhibits PRC2/EED-EZH1 and PRC2/EED-EZH2 complex function by inhibiting EZH1/EZH2 methyltransferase activity, thereby causing down-regulation of histone H3 trimethylation at 'Lys-27' (H3K27me3) (PubMed:31086175). Probably inhibits methyltransferase activity by limiting the stimulatory effect of cofactors such as AEBP2 and JARID2 (By similarity). Inhibits H3K27me3 deposition during spermatogenesis and oogenesis (PubMed:31451685).|||Interacts with PRC2/EED-EZH1 complex member EZH1 and with PRC2/EED-EZH2 complex member EZH2; the interaction blocks EZH1/EZH2 methyltransferase activity (PubMed:31086175). Interacts (via C-terminus) with SUZ12 which is a member of the PRC2/EED-EZH1 and PRC2/EED-EZH2 complexes (By similarity).|||No overt developmental defects with mutant adults appearing indistinguishable from wild-type (PubMed:31451685). Two-fold increase in H3K27me2 and H3K27me3 levels in germ cells in testis but males display normal testis-to-body weight ratio and normal fertility (PubMed:31451685). Increased H3K27me3 levels in postnatal oocytes and slight increase in the number of oocytes with lagging chromosomes (PubMed:31451685). No significant differences in the number of primordial, primary and secondary/antral follicles of pre-pubertal females but older females show a reduced number of follicles at 16 weeks (PubMed:31451685). Females have smaller ovaries and give rise to fewer progeny as they age (PubMed:31451685).|||Nucleus http://togogenome.org/gene/10090:Tas1r3 ^@ http://purl.uniprot.org/uniprot/Q925D8 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 3 family. TAS1R subfamily.|||Cell membrane|||Expressed in circumvallate, foliate and fungiform taste papillae as well as in taste buds on the palate. Also expressed in testis. Not expressed in brain, heart, kidney, liver or spleen. The topographic distribution in various taste papillae is different from those of other T1R members.|||Forms homodimers or heterodimers with TAS1R1 and TAS1R2.|||Putative taste receptor. TAS1R1/TAS1R3 responds to the umami taste stimulus (the taste of monosodium glutamate) and also to most of the 20 standard L-amino acids, but not to their D-enantiomers or other compounds. TAS1R2/TAS1R3 recognizes diverse natural and synthetic sweeteners. TAS1R3 is essential for the recognition and response to the disaccharide trehalose. Sequence differences within and between species can significantly influence the selectivity and specificity of taste responses.|||The Thr-60 variant is predicted to introduce a novel N-linked glycosylation site at Asn-58. The addition of even a short carbohydrate group at Asn-58 is predicted to disrupt one of the contact surfaces required for stability of a dimer. Therefore a Thr-60 variant N-glycosylated at Asn-58 is predicted to be precluded from forming homodimers or heterodimers. http://togogenome.org/gene/10090:Slc25a3 ^@ http://purl.uniprot.org/uniprot/G5E902|||http://purl.uniprot.org/uniprot/Q8VEM8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the mitochondrial carrier (TC 2.A.29) family.|||Inorganic ion transporter that transports phosphate or copper ions across the mitochondrial inner membrane into the matrix compartment (By similarity). Mediates proton-coupled symport of phosphate ions necessary for mitochondrial oxidative phosphorylation of ADP to ATP (By similarity). Transports copper ions probably in the form of anionic copper(I) complexes to maintain mitochondrial matrix copper pool and to supply copper for cytochrome C oxidase complex assembly (PubMed:29237729). May also play a role in regulation of the mitochondrial permeability transition pore (mPTP) (By similarity).|||Interacts with PPIF; the interaction is impaired by CsA.|||Membrane|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Ndufaf3 ^@ http://purl.uniprot.org/uniprot/Q9JKL4 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).|||Interacts with NDUFAF4, NDUFS2 and NDUFS3.|||Mitochondrion inner membrane|||Nucleus|||Strongly expressed in testis and weakly expressed in the epididymis. Expressed in spermatocytes. http://togogenome.org/gene/10090:Vstm5 ^@ http://purl.uniprot.org/uniprot/Q9D806 ^@ Developmental Stage|||Disruption Phenotype|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Can homooligomerize through cis interactions within the same cell membrane.|||Cell adhesion-like membrane protein of the central nervous system (CNS) which modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Involved in the formation of neuronal dendrites and protrusions including dendritic filopodia. In synaptogenesis, regulates synapse formation by altering dendritic spine morphology and actin distribution. Promotes formation of unstable neuronal spines such as thin and branched types. Regulates neuronal morphogenesis and migration during cortical development in the brain.|||Cell membrane|||Expressed in the ventral spinal cord, with strong expression in a subset of motor neurons, and in a subset of sensory neurons at embryonic day (E) 15.5 (PubMed:25826454). In the developing brain, expressed at low levels on 11 dpc, rapidly increasing to peak at postnatal day (P) 1, a period corresponding to the early stage of postmitotic neuronal differentiation when neuronal morphogenesis or synapse formation occurs, and then gradually decreasing (PubMed:27683913).|||Highly expressed in the central nervous system (CNS), with the highest expression in thalamus, hippocampus, cerebrum, midbrain and spinal cord. Also highly expressed in stomach, kidney and small intestine.|||N-glycosylated.|||RNAi-mediated knockdown mice have significantly lower density of dendritic filopodia and dendritic spines in embryonic hippocampal neurons. Lower density of excitatory synapses and significantly decreased dendritic spine to shaft ratio of F-actin in the later stages of neuron development. Aberrant neuronal migration in the cerebral cortex of developing mouse embryo. Neurons settle in the marginal zone (MZ) closer to the pial side and the corresponding percentage of neurons is decreased in the dense cortical plate (dCP), reflecting the overmigration of those neurons. Neurons in the upper cortical plate (UCP) result in a small but significant reduction in both the number of dendrites and average dendrite length. Neurons of embryonic brains show much lower levels of spines with the density of mushroom spines markedly decreased.|||axon|||dendrite http://togogenome.org/gene/10090:Cuzd1 ^@ http://purl.uniprot.org/uniprot/P70412 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Tissue Specificity ^@ First detected in uterus 6 days prior to birth, increases daily to reach maximum levels 3 days before birth, abruptly decreases during the last 3 days of pregnancy and is almost undetectable by the first day after birth.|||Highly expressed in pancreatic acinar cells. Also expressed in epithelium of the uterus during late pregnancy but not detected in non-pregnant uterus or in a variety of other adult and fetal tissues.|||Localized to zymogen granules, where it functions in trypsinogen activation (PubMed:12401800). May indirectly regulate cell motility, cell-cell and cell/extracellular matrix interactions (By similarity).|||Mice display increased severity of secretagogue- and diet-induced pancreatitis which seems to be due to impaired activation of trypsin.|||Zymogen granule membrane http://togogenome.org/gene/10090:Lta ^@ http://purl.uniprot.org/uniprot/P09225|||http://purl.uniprot.org/uniprot/Q542S2 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the tumor necrosis factor family.|||Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (By similarity). In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo.|||Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo.|||Homotrimer, and heterotrimer of either two LTB and one LTA subunits or (less prevalent) two LTA and one LTB subunits. Interacts with TNFRSF14.|||Membrane|||Secreted http://togogenome.org/gene/10090:Zc2hc1c ^@ http://purl.uniprot.org/uniprot/Q8CB75|||http://purl.uniprot.org/uniprot/Q8CCG1 ^@ Similarity ^@ Belongs to the ZC2HC1 family. http://togogenome.org/gene/10090:Col11a2 ^@ http://purl.uniprot.org/uniprot/Q64739 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the fibrillar collagen family.|||May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).|||Trimers composed of three different chains: alpha 1(XI), alpha 2(XI), and alpha 3(XI). Alpha 3(XI) is a post-translational modification of alpha 1(II). Alpha 1(V) can also be found instead of alpha 3(XI)=1(II) (By similarity).|||extracellular matrix http://togogenome.org/gene/10090:Inava ^@ http://purl.uniprot.org/uniprot/Q7TN12 ^@ Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit ^@ After infection with Citrobacter rodentium, mutants show significantly increased bacterial loads at day 5 compared to wild-types. They are able to control the infection by day 12 post-infection, they exhibit significantly shortened colon length. They don't have impaired cytokine response (PubMed:29420262). Mutants also exhibit impaired recovery from dextran sodium sulfate-induces colitis, they show increased body weight loss and reduced colon length (PubMed:29420262).|||Cytoplasm|||Expressed in peripheral macrophages and intestinal myeloid-derived cells, is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance. Upon stimulation of a broad range of PRRs (pattern recognition receptor) such as NOD2 or TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9, associates with YWHAQ/14-3-3T, which in turn leads to the recruitment and activation of MAP kinases and NF-kappa-B signaling complexes that amplifies PRR-induced downstream signals and cytokine secretion (By similarity). In the intestine, regulates adherens junction stability by regulating the degradation of CYTH1 and CYTH2, probably acting as substrate cofactor for SCF E3 ubiquitin-protein ligase complexes. Stabilizes adherens junctions by limiting CYTH1-dependent ARF6 activation (PubMed:29420262).|||Interacts with IRAK1, NOD2 and RIPK2; the interaction takes place upon PRR stimulation. Interacts with YWHAQ/14-3-3T; the interaction increases upon PRR stimulation and is required for cellular signaling pathway activation and cytokine secretion. Interacts (via N-terminal domain) with CYTH1 and CYTH2 (via their N-terminal domains). Interacts with FBXW11 and BTRC; associates with SCF E3 ubiquitin-protein ligase complexes (By similarity).|||Nucleus http://togogenome.org/gene/10090:Nt5dc2 ^@ http://purl.uniprot.org/uniprot/Q91X76 ^@ Cofactor|||Similarity ^@ Belongs to the 5'(3')-deoxyribonucleotidase family.|||Binds 1 Mg(2+) ion per subunit. http://togogenome.org/gene/10090:Lipf ^@ http://purl.uniprot.org/uniprot/Q9CPP7 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the AB hydrolase superfamily. Lipase family.|||Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol (By similarity). Shows a preferential hydrolysis at the sn-3 position of triacylglycerol (By similarity).|||Secreted http://togogenome.org/gene/10090:Tdpoz4 ^@ http://purl.uniprot.org/uniprot/Q6YCH2 ^@ Developmental Stage|||Similarity ^@ Belongs to the Tdpoz family.|||Strongly expressed in 2-cell embryos. No expression detected in other embryonic stages or in adult testis. http://togogenome.org/gene/10090:2610528J11Rik ^@ http://purl.uniprot.org/uniprot/Q9CQM1 ^@ Function|||Subcellular Location Annotation|||Tissue Specificity ^@ Cell membrane|||Early endosome|||Expressed in stomach, kidney, large and small intestine and kidney.|||May be involved in membrane trafficking between endosomes and plasma membrane.|||Membrane|||Recycling endosome http://togogenome.org/gene/10090:Mcat ^@ http://purl.uniprot.org/uniprot/Q8R3F5 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the type II malonyltransferase family.|||Catalyzes the transfer of a malonyl moiety from malonyl-CoA to the free thiol group of the phosphopantetheine arm of the mitochondrial ACP protein (NDUFAB1). This suggests the existence of the biosynthesis of fatty acids in mitochondria.|||Mitochondrion http://togogenome.org/gene/10090:Kcnk6 ^@ http://purl.uniprot.org/uniprot/Q3TBV4|||http://purl.uniprot.org/uniprot/Q3TQ68|||http://purl.uniprot.org/uniprot/Q3V1G1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.|||Membrane http://togogenome.org/gene/10090:Vmn1r197 ^@ http://purl.uniprot.org/uniprot/Q8R265 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mtnr1b ^@ http://purl.uniprot.org/uniprot/Q3SXF8 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Clcn2 ^@ http://purl.uniprot.org/uniprot/Q9R0A1 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.|||Cell membrane|||Expressed in the adrenal gland and brain.|||Hyperpolarization-activated chloride currents are absent in glomerulosa cells of knockout mice.|||Phosphorylated. Activated by dephosphorylation.|||The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels (By similarity).|||Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport (By similarity). Involved in the regulation of aldosterone production. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated Ca2+ channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (By similarity). http://togogenome.org/gene/10090:Wdr24 ^@ http://purl.uniprot.org/uniprot/Q8CFJ9 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Autoubiquitinated; MIOS is required to prevent autoubiquitination.|||Belongs to the WD repeat WDR24 family.|||Catalytic component of the GATOR2 complex, a multiprotein complex that acts as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:36528027). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (By similarity). GATOR2 probably acts as a E3 ubiquitin-protein ligase toward GATOR1 (By similarity). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (By similarity). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (By similarity). In addition to its role in regulation of the mTORC1 complex, promotes the acidification of lysosomes and facilitates autophagic flux (By similarity). Within the GATOR2 complex, WDR24 constitutes the catalytic subunit that mediates 'Lys-6'-linked ubiquitination of NPRL2 (By similarity).|||Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids. SESN1, SESN2 and SESN3 convey leucine availability via direct interaction with SEH1L and WDR24.|||Lysosome membrane|||Phosphorylation at Ser-155 by AMPK in response to glucose deprivation inactivates WDR24 by promoting interaction with 14-3-3 proteins, such as YWHAG, preventing assembly of the GATOR2 complex.|||The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated. http://togogenome.org/gene/10090:Lrrc38 ^@ http://purl.uniprot.org/uniprot/A2VDH3 ^@ Domain|||Function|||Subcellular Location Annotation|||Subunit ^@ Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium (By similarity).|||Cell membrane|||Interacts with KCNMA1.|||The transmembrane domain is necessary for interaction with KCNMA1. http://togogenome.org/gene/10090:Rnf6 ^@ http://purl.uniprot.org/uniprot/Q9DBU5 ^@ Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the RNF12 family.|||Cytoplasm|||E3 ubiquitin-protein ligase mediating 'Lys-48'-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation (PubMed:16204183). Negatively regulates axonal outgrowth through regulation of the LIMK1 turnover (PubMed:16204183). Mediates 'Lys-6' and 'Lys-27'-linked polyubiquitination of AR/androgen receptor thereby modulating its transcriptional activity (By similarity). May also bind DNA and function as a transcriptional regulator (PubMed:11971979). Mediates polyubiquitination of QKI in macrophages, leading to its degradation (PubMed:36088389).|||Expressed in the floor plate and ventral portions of the developing neural tube of 12.5 dpc to 13 dpc mouse embryos. Found in developing neuronal projections (at protein level).|||Nucleus|||PML body|||Widely expressed with higher expression in the testis in both germ cells and Sertoli cells.|||axon http://togogenome.org/gene/10090:Or2p2 ^@ http://purl.uniprot.org/uniprot/Q8VFG4 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Grhl3 ^@ http://purl.uniprot.org/uniprot/Q5FWH3 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ At 8.5 dpc, expression is confined to the non-neural ectoderm immediately adjacent to the neural plate, which was undergoing folding to form the neural tube. At later time points, more widespread expression is observed in the surface ectoderm, with a progressive increase until 15.5 dpc. Also expressed in other tissues lined by squamous epithelium, including the oral cavity, urogenital sinus and anal canal.|||Belongs to the grh/CP2 family. Grainyhead subfamily.|||GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxal lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.|||Homodimer, also forms heterodimers with GRHL1 and GRHL2 (By similarity). Interacts with LMO4 (PubMed:16949565).|||Mutant pups display neural tube defects and don't survive to weaning. During embryogenesis, fail to form the epidermal barrier and exhibit defective neural tube closure and embryonic wound repair. The epidermis show a severe barrier function defect associated with impaired differentiation of the epidermis, including defects of the stratum corneum, extracellular lipid composition and cell adhesion in the granular layer. Embryos have thoracolumbosacral spina bifida and curled tail, and 2% have coincident exencephaly. Embryos are smaller than their control littermates, exhibit failed eyelid fusion, the penetrance of which is influenced by genetic background, and shorter intestine with blood in the lumen (PubMed:14608380, PubMed:16949565, PubMed:21081122). Embryos have oral bilateral epithelial adhesions because of the loss of periderm and a cleft palate in some cases (PubMed:24360809). LMO4:GRHL3 double knockout embryos show significantly more frequent exencephaly than that found in single knockouts. Similarly, open-eye phenotype was more penetrant in double knockout mice. Double mutants show an enhancement of the epidermal terminal differentiation defect (PubMed:16949565).|||Nucleus|||Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes. Essential for epidermal differentiation and barrier formation at the end of embryogenesis with TGM3 as critical direct target (PubMed:21081122, PubMed:20654612, PubMed:25347468). Exhibits functional redundancy with GRHL2 in epidermal morphogenetic events such as eyelid fusion and epidermal wound repair (PubMed:21081122). Despite being dispensable during normal epidermal homeostasis in the adulthood, is again required for barrier repair after immune-mediated epidermal damage, regulates distinct gene batteries in embryonic epidermal differentiation and adult epidermal barrier reformation after injury (PubMed:25347468). Plays unique and cooperative roles with GRHL2 in establishing distinct zones of primary neurulation. Essential for spinal closure, functions cooperatively with GRHL2 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (PubMed:14608380, PubMed:20654612). Also required for proper development of the oral periderm (PubMed:24360809). No genetic interaction with GRHL1, no functional cooperativity due to diverse target gene selectivity (PubMed:21081122). http://togogenome.org/gene/10090:Krt2 ^@ http://purl.uniprot.org/uniprot/Q3TTY5 ^@ Developmental Stage|||Disease Annotation|||Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the intermediate filament family.|||Cytoplasm|||Defects in Krt2 are a cause of ichthyosis bullosa of siemens (IBS). IBS is a rare autosomal dominant disorder displaying a type of epidermolytic hyperkeratosis characterized by extensive blistering from birth. Hyperkeratoses and shedding of the outer layers of the epidermis (molting) are observed in later weeks.|||Expressed predominantly in the suprabasal layers of the plantar epidermis outside of the footpads (at protein level) (PubMed:26603179). Expressed in the suprabasal layers of the interfollicular epidermis of the ear, in the interscale regions distant from the hair follicles in the tail, and in the soles of the footpads (at protein level) (PubMed:24751727). Expressed mainly in the middle spinous and granular cells of the epidermis of adult tail, nipple and footsole skin. Also found in ear.|||Heterotetramer of two type I and two type II keratins. Associates with KRT10.|||Induction occurs during the first 2 weeks after birth, being first observed in the epidermis of tail then the footpad and later in the ear.|||Mice are viable and display no differences in size and body weight (PubMed:24751727, PubMed:26603179). Scaly skin and increased pigmentation on ears and hyperkeratotic calluses on the soles and toe pads within 6 weeks of birth (PubMed:24751727, PubMed:26603179). Prominent acanthosis, orthokeratotic hyperkeratosis in the epidermis of the ear and to a lesser extent in the epidermis of the tail and the palm skin caused by an increase in cell proliferation and thicker granular layer (PubMed:24751727). Keratinocyte differentiation is disorganized, large coalescent granules are accumulated, and cytolysis is evidence in the ear skin (PubMed:24751727). Increase in defective corneocytes and an increase in transepidermal water loss in ear skin (PubMed:24751727). Suprabasal keratinocytes contain distinct spongy clumps of Krt10 filaments (PubMed:24751727). Increase in Tslp and Il18 expression, and abundance of T-cells and mast cells in ear skin (PubMed:24751727). Increase in expression of Krt1, Krt10, Krt16, Flg and Loricrin in the ear epidermis (PubMed:24751727). Krt1, Krt5, Krt10, Krt16, Flg and Loricrin all show disordered localization within the ear epidermis (PubMed:24751727). Krt10 specifically show aggregation within the cytoplasm in epidermal cells of the ear (PubMed:24751727). Show no epidermal aberrations of the footpads (PubMed:26603179). Double knockout mice of KRT2 and KRT10 are viable and display no differences in size and body weight (PubMed:26603179). Show a more severe plantar epidermis phenotype as in single KRT2 knockout mice (PubMed:26603179).|||Probably contributes to terminal cornification (By similarity). Associated with keratinocyte activation, proliferation and keratinization (By similarity). Required for maintenance of corneocytes and keratin filaments in suprabasal keratinocytes in the epidermis of the ear, potentially via moderation of expression and localization of keratins and their partner proteins (PubMed:24751727). Plays a role in the establishment of the epidermal barrier on plantar skin (PubMed:26603179).|||There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa). http://togogenome.org/gene/10090:Phactr2 ^@ http://purl.uniprot.org/uniprot/A1L3S9|||http://purl.uniprot.org/uniprot/B1AVN9|||http://purl.uniprot.org/uniprot/F7D4H5|||http://purl.uniprot.org/uniprot/Q3UQ19|||http://purl.uniprot.org/uniprot/Q3UTF8 ^@ Similarity|||Subunit ^@ Belongs to the phosphatase and actin regulator family.|||Binds PPP1CA and actin. http://togogenome.org/gene/10090:Zfp382 ^@ http://purl.uniprot.org/uniprot/B2RXC5 ^@ Caution|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||Functions as a sequence-specific transcriptional repressor.|||Interacts with TRIM28; enhances the transcriptional repressor activity.|||It is uncertain whether Met-1 or Met-37 is the initiator.|||Nucleus http://togogenome.org/gene/10090:Oas1a ^@ http://purl.uniprot.org/uniprot/P11928 ^@ Activity Regulation|||Developmental Stage|||Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the 2-5A synthase family.|||C-terminal prenylated.|||Cytoplasm|||Detected 5 weeks after birth in developing ovary and spleen (PubMed:27663720). Expressed in fully grown, germinal vesicle (GV)-intact oocytes, in oocytes at the metaphase II stage and in the 2- to 8-cell embryos (PubMed:15899864).|||Endoplasmic reticulum|||Expressed in oocytes and granulosa cells of ovary, in intestine, stomach, spleen and uterus (at protein level) (PubMed:15899864). Expressed at high levels in the digestive tract and lymphoid organs (PubMed:12396720). Expressed in ovary and spleen (PubMed:27663720).|||Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L.|||Microsome|||Mitochondrion|||Monomer (By similarity). Homotetramer (By similarity). Interacts with OAS1D; the interaction inhibits OAS1A catalytic activity (PubMed:15899864).|||Nucleus|||Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators.|||Up-regulated in response to the type I interferon IFNB1, in a STAT1 and STAT2-dependent manner (PubMed:1709495, PubMed:22305621). Induced by polyinosinic:polycytidylic acid (poly I:C) (PubMed:15899864, PubMed:27663720). http://togogenome.org/gene/10090:Gbp3 ^@ http://purl.uniprot.org/uniprot/Q61107 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.|||Brain, lung, heart, spleen, kidney, liver and intestine.|||By IFNG/IFN-gamma, IFNB1/IFN-beta and TNF-alpha (PubMed:9659399, PubMed:18025219). Up-regulated upon infection by T.gondii or L.monocytogenes (PubMed:18025219).|||Cytoplasm|||Golgi apparatus membrane|||Heterodimer with other family members, including GBP1, GBP2 and GBP5. Dimerization regulates subcellular location.|||Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:24739961, PubMed:24715728). Hydrolyzes GTP very efficiently; GDP rather than GMP is the major reaction product (PubMed:9659399). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (PubMed:24739961, PubMed:24715728). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (PubMed:24739961, PubMed:24715728). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis, such as Gm12250/Irgb10: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (PubMed:24739961, PubMed:24715728). May play a role in erythroid differentiation (PubMed:9659399).|||perinuclear region http://togogenome.org/gene/10090:Mrps24 ^@ http://purl.uniprot.org/uniprot/Q9CQV5 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the universal ribosomal protein uS3 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion http://togogenome.org/gene/10090:Ccdc90b ^@ http://purl.uniprot.org/uniprot/Q8C3X2 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CCDC90 family.|||Interacts with MCU.|||Mitochondrion membrane http://togogenome.org/gene/10090:Rad54l ^@ http://purl.uniprot.org/uniprot/P70270 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated. Acetylation promotes interaction with BRD9, and subsequently with RAD54, which is essential for homologous recombination (HR).|||Belongs to the SNF2/RAD54 helicase family.|||Hardly detectable in most tissues. Dramatically increased in thymus, spleen and testis.|||Homohexamer (By similarity). Interacts (via N-terminus) with RAD51 (By similarity). Interacts with NAP1L1 (By similarity). Interacts with BRD9; this interaction orchestrates RAD51-RAD54 complex formation (By similarity).|||Nucleus|||Phosphorylated. Phosphorylation at Ser-572 by NEK1 specifically in G2 phase allows efficient removal of RAD51 filaments from DNA.|||Plays an essential role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Plays also an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA (By similarity). Deficiency also resulted in an increased frequency of end-to-end chromosome fusions involving telomeres compared to the controls, suggesting a putative role in telomere capping. Non-homologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. LIG4 and RAD54L cooperate to support cellular proliferation, repair spontaneous DSBs, and prevent chromosome and single chromatid aberrations (PubMed:10209103, PubMed:10757799, PubMed:12218123, PubMed:12531026, PubMed:12548566, PubMed:12897131, PubMed:15175260, PubMed:9108475).|||The nucleus of a mouse embryonic stem (ES) cell contains on average 2.4 x 10(5) molecules. http://togogenome.org/gene/10090:Cib1 ^@ http://purl.uniprot.org/uniprot/Q9Z0F4 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Induction|||Miscellaneous|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Apical cell membrane|||Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis. Involved in bone marrow megakaryocyte differentiation by negatively regulating thrombopoietin-mediated signaling pathway. Participates in the endomitotic cell cycle of megakaryocyte, a form of mitosis in which both karyokinesis and cytokinesis are interrupted. Plays a role in integrin signaling by negatively regulating alpha-IIb/beta3 activation in thrombin-stimulated megakaryocytes preventing platelet aggregation. Up-regulates PTK2/FAK1 activity, and is also needed for the recruitment of PTK2/FAK1 to focal adhesions; it thus appears to play an important role in focal adhesion formation. Positively regulates cell migration on fibronectin in a CDC42-dependent manner, the effect being negatively regulated by PAK1. Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. Down-regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Involved in sphingosine kinase SPHK1 translocation to the plasma membrane in a N-myristoylation-dependent manner preventing TNF-alpha-induced apoptosis. Regulates serine/threonine-protein kinase PLK3 activity for proper completion of cell division progression. Plays a role in microtubule (MT) dynamics during neuronal development; disrupts the MT depolymerization activity of STMN2 attenuating NGF-induced neurite outgrowth and the MT reorganization at the edge of lamellipodia. Promotes cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway. Stimulates calcineurin PPP3R1 activity by mediating its anchoring to the sarcolemma. In ischemia-induced (pathological or adaptive) angiogenesis, stimulates endothelial cell proliferation, migration and microvessel formation by activating the PAK1 and ERK1/ERK2 signaling pathway. Promotes also cancer cell survival and proliferation. May regulate cell cycle and differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.|||Cell membrane|||Cytoplasm|||Expressed in the heart at 16 dpc (at protein level) (PubMed:20639889). On P7, detected mainly at the apical surface of hair cells (PubMed:16418530). In outer hair cells, it was observed in the kinocilium and in the basal body region at the periphery of the hair cell (PubMed:16418530).|||Expressed strongly in Sertoli cells, weakly in pachytene spermatocytes, round spermatids and condensing spermatids (at protein level) (PubMed:16982698). Expressed in testis (PubMed:16982698). Expressed in cardiac myocytes and endothelial cells (PubMed:17975111, PubMed:18989529, PubMed:20639889). Expressed in heart, liver, spleen, lung, kidney, brain and inner ear (PubMed:29255404). In the inner ear, expressed in the vestibule, basilar membrane and spiral ganglion cells (PubMed:29255404).|||Membrane|||Mice grow normally and are healthy; other family members (CIB2, CIB3 and CIB4) may probably compensate for CIB1 loss (PubMed:18989529). Males are sterile: spermatogenic cells can complete both mitotic and meiotic divisions, but postmeiotic spermatids do not develop normally and sperm is not produced (PubMed:16982698). Display increased bone marrow megakaryocytes and circulating platelets (PubMed:22128142). Mice display tail bleeding time increase, impaired thrombus formation and angiogenesis defect after ischemia (PubMed:19691476). Show compromised tumor growth (PubMed:20804551). Does not affect auditory function (PubMed:29255404).|||Monomer. Interacts with the heterodimeric integrin alpha-IIb/beta3 (ITGA2B-ITGB3). Interacts with ITGA2B (via cytoplasmic domain); the interaction is direct and calcium-dependent. Interacts with the protein kinases PLK2/SNK and PRKDC (via the region immediately upstream of the kinase domain). Interacts with PLK3; the interaction inhibits PLK3 kinase activity. Interacts with PSEN2. Interacts (via C-terminus) with F8. Interacts with NBR1 (via C-terminus). Interacts with FEZ1 (via C-terminus). Interacts with UBR5 (via C-terminus); the interaction is sensitive to DNA damage, and may target CIB1 for ubiquitin-mediated degradation. Interacts with IFI6; the interaction is direct. Interacts with BCL2. Interacts with TAS1R2 (via C-terminus); the interaction is independent of the myristoylation state of CIB1. Interacts with ITPR3; the interaction occurs in a calcium dependent manner. Interacts with PTK2/FAK1. Interacts with MAP3K5; the interaction inhibits MAP3K5 activation by phosphorylation, and its subsequent interaction with TRAF2. Interacts (via C-terminal region) with STMN2 (via the N-terminal region); the interaction is direct, occurs in a calcium-dependent manner and attenuates the STMN2-induced neurite outgrowth inhibition. Interacts with SPHK1, the interaction occurs in a calcium-dependent manner. Interacts with ITGA2B (via C-terminal cytoplasmic tail); the interaction occurs upon platelet aggregation and is stabilized/increased in a calcium and magnesium-dependent manner. Interacts with PAK1 (via N-terminal region); the interaction is direct and occurs in a calcium-dependent manner. Interacts with RAC3 (via C-terminal region); the interaction induces their association with the cytoskeleton upon alpha-IIb/beta3 integrin-mediated adhesion. Interacts with ITGA5 and ITGAV (By similarity). Interacts with MYO1C. Interacts with ITGA2B (via C-terminal cytoplasmic tail region). Interacts (via C-terminal region) with PPP3R1 isoform 1 and isoform 2; the interactions increase upon cardiomyocytes hypertrophy. Interacts with CACNA1C; the interaction increases upon cardiomyocytes hypertrophy. Interacts and forms a complex with TMC6 and TMC8 (By similarity).|||Nucleus|||Perikaryon|||The EF-hands may also bind magnesium ions in the presence of high Mg(2+) levels and low Ca(2+) levels.|||The binding of either calcium or magnesium significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form).|||Up-regulated upon cardiomyocytes hypertrophy (at protein level).|||centrosome|||cytoskeleton|||filopodium tip|||growth cone|||lamellipodium|||neuron projection|||perinuclear region|||ruffle membrane|||sarcolemma http://togogenome.org/gene/10090:Aox1 ^@ http://purl.uniprot.org/uniprot/G3X8P9|||http://purl.uniprot.org/uniprot/O54754 ^@ Cofactor|||Developmental Stage|||Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ AOX genes evolved from a xanthine oxidoreductase ancestral precursor via a series of gene duplication and suppression/deletion events. Different animal species contain a different complement of AOX genes encoding an equivalent number of AOX isoenzymes. In mammals, the two extremes are represented by certain rodents such as mice and rats, which are endowed with 4 AOX genes, and by humans, whose genome is characterized by a single active gene (PubMed:23263164).|||Belongs to the xanthine dehydrogenase family.|||Binds 1 FAD per subunit.|||Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.|||Binds 2 [2Fe-2S] clusters per subunit.|||Binds 2 [2Fe-2S] clusters.|||Cytoplasm|||Expressed in adult liver but not in neonatal or embryonic liver. Not detected in preadipocytes but strongly induced in mature adipocytes.|||Highest expression in esophagus. Moderately low expression in lung, liver, heart, Harderian gland, olfactory mucosa, skin and testis. In brain, expression is very high in choroid plexus, high in hind brain and low in hippocampus and cerebellum. In spinal cord expression is strongest in anterior horns. Low expression detected in spleen and eye. AOX1 expression in the livers of mice is approximately seven times greater in males than females.|||Homodimer.|||Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Also plays a role in the reductive metabolism of the xenobiotic imidacloprid (IMI) via its nitroreduction to nitrosoguanidine (IMI-NNO) and aminoguanidine (IMI-NNH(2)). Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis. Cannot use xanthine and hypoxanthine as substrate.|||Repressed by pioglitazone, fenofibrate and PPARA agonists. Induced by testosterone. http://togogenome.org/gene/10090:Ubr2 ^@ http://purl.uniprot.org/uniprot/Q3UPU3|||http://purl.uniprot.org/uniprot/Q6WKZ8 ^@ Disruption Phenotype|||Domain|||Function|||Induction|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the UBR1 family.|||Chromosome|||E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:14585983, PubMed:31268597, PubMed:30872531). Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (PubMed:14585983, PubMed:31268597, PubMed:30872531). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (PubMed:14585983, PubMed:20080676). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (By similarity). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (PubMed:28708824). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (PubMed:28806172). Catalyzes ubiquitination and degradation of the N-terminal part of Nlrp1b following Nlrp1b activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:31268597, PubMed:30872531).|||Highly expressed in skeletal muscle. Also expressed in heart, kidney and testis. Expressed in acinar cells of the pancreas. In testes, expressed primarily in spermatocytes. Expressed in cerebellum (PubMed:28806172).|||In models of cancer cachexia, induced specifically at the onset and during the progression of muscle wasting.|||Interacts with UBE2B; promotes the UBE2B-H2A interaction and the ubiquitination of histone H2A by UBE2B and UBR2 (PubMed:14585983, PubMed:20080676). Interacts with RECQL4 (By similarity). Interacts with Tex19.1 and Tex19.2; does not lead to Tex19.1 degradation and stabilizes it (PubMed:21103378). Interacts with L1RE1 (PubMed:28806172). Interacts with CASP8 (By similarity). Interacts with ATXN3 (By similarity). Interacts with UBE2O (PubMed:31268597).|||Intron retention.|||Male mice are viable but not fertile, due to massive apoptosis of spermatocytes. They have a reduction of testis weight of 68% and no detectable sperm in their epididymis. The seminiferous tubules contain reduced numbers of post-meiotic round, elongated spermatids and accumulation of pyknotic and zygotene-like nuclei. Female mice show severe prenatal lethality, but the rare surviving are fertile. Fibroblast cells display spontaneous chromosome instability and fragility (PubMed:14585983, PubMed:16488448, PubMed:28708824). UBR1 and UBR2 double knockout embryos die at midgestation, with defects in neurogenesis and cardiovascular development. These defects included reduced proliferation as well as precocious migration and differentiation of neural progenitor cells (PubMed:16606826).|||Nucleus|||The RING-H2 zinc finger is an atypical RING finger with a His ligand in place of the fourth Cys of the classical motif.|||The UBR-type zinc finger forms a pocket that mediates recognition of type 1 N-degrons. It exhibits preference for Arginine in first position, has poor affinity for histidine, and doesn't bind acetylated peptides (By similarity).|||Ubiquitin ligase protein which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. http://togogenome.org/gene/10090:Card10 ^@ http://purl.uniprot.org/uniprot/P58660 ^@ Caution|||Disruption Phenotype|||Function|||Subunit|||Tissue Specificity ^@ CARD10 and BCL10 bind to each other by CARD-CARD interaction. They both participate in a complex with MALT1, where MALT1 binds to BCL10 (PubMed:28717989). Interacts with TMEM43; this interaction is essential for EGFR-mediated NF-kappa-B activation (By similarity).|||Deletion mice show impaired tissue repairing. In addition, more infiltration of inflammatory cells was found in deletion mice compared with control mice.|||Highly expressed in kidney, heart followed by brain, lung, liver, skeletal muscle and testis.|||Scaffold protein that plays an important role in mediating the activation of NF-kappa-B via BCL10 or EGFR.|||Supposed to contain a SH3, a PDZ and a guanylate kinase-like domain. But none of these 3 domains are detected by PROSITE, Pfam or SMART. http://togogenome.org/gene/10090:Pi4kb ^@ http://purl.uniprot.org/uniprot/Q8BKC8 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.|||Endomembrane system|||Golgi apparatus|||Golgi apparatus membrane|||Inhibited by wortmannin. Increased kinase activity upon interaction with NCS1/FREQ.|||Interacts with ARF1 and ARF3 in the Golgi complex, but not with ARF4, ARF5 or ARF6 (By similarity). Interacts with NCS1/FREQ in a calcium-independent manner. Interacts with CALN1/CABP8 and CALN2/CABP7; in a calcium-dependent manner; this interaction competes with NCS1/FREQ binding (By similarity). Interacts with ACBD3. Interacts with ARMH3, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN (By similarity). Interacts with GGA2 (via VHS domain); the interaction is important for PI4KB location at the Golgi apparatus membrane (By similarity). Interacts with ATG9A.|||Mitochondrion outer membrane|||Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation (By similarity). Involved in Golgi-to-plasma membrane trafficking (By similarity). May play an important role in the inner ear development.|||Rough endoplasmic reticulum membrane http://togogenome.org/gene/10090:Fam234a ^@ http://purl.uniprot.org/uniprot/Q8C0Z1 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the FAM234 family.|||Membrane http://togogenome.org/gene/10090:Trim34b ^@ http://purl.uniprot.org/uniprot/K7N6K2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the TRIM/RBCC family.|||Cytoplasm|||Functions as antiviral protein and contributes to the defense against retroviral infections (By similarity). Acts as a capsid-specific restriction factor with the help of TRIM5 and prevents infection from non-host-adapted retroviruses. During influenza A virus infection, promotes programmed cell death by targeting ZBP1 for 'Lys-63'-linked polyubiquitination. In turn, promotes ZBP1 recruitment of RIPK3 to mediate virus-induced programmed necrosis (By similarity). Negatively regulates the function of mitochondria by enhancing mitochondrial depolarization leading to cytochrome c release and mitochondria-dependent apoptosis. Promotes also the formation of multinucleated giant cells by means of cell fusion and phagocytosis in epithelial cells (By similarity). Regulates intestinal inflammation by controlling the exocytosis of the major component of colonic mucus MUC2 from colonic goblet cells (PubMed:32094504).|||Homotrimer. Interacts (via B-box and SPRY domain) with TRIM5.|||Mitochondrion|||Trim34a- and TRIM34b-deficient mice show an impaired integrity of the inner mucus layer. http://togogenome.org/gene/10090:H2bc14 ^@ http://purl.uniprot.org/uniprot/B2RTK3|||http://purl.uniprot.org/uniprot/P10854 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage (By similarity). H2BS6ADPr promotes recruitment of CHD1L (By similarity). Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks (By similarity). Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (PubMed:32822587).|||Belongs to the histone H2B family.|||Chromosome|||Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.|||Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.|||GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).|||Hydroxybutyrylation of histones is induced by starvation.|||Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.|||Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons (By similarity).|||Nucleus|||Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation (PubMed:15197225, PubMed:16039583). Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination (PubMed:15197225). Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription (PubMed:20647423, PubMed:32822587).|||The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. http://togogenome.org/gene/10090:Il15 ^@ http://purl.uniprot.org/uniprot/P48346|||http://purl.uniprot.org/uniprot/Q1AHQ6|||http://purl.uniprot.org/uniprot/Q1AHQ7|||http://purl.uniprot.org/uniprot/Q3U1Z6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation ^@ Belongs to the IL-15/IL-21 family.|||By type I interferons, double-stranded RNA, or lipopolysaccharides.|||Cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems (PubMed:8757333, PubMed:11466332). Stimulates the proliferation and activation of natural killer cells, T-cells and B-cells and promotes the secretion of several cytokines (PubMed:8757333). In monocytes, induces the production of IL8 and monocyte chemotactic protein 1/CCL2, two chemokines that attract neutrophils and monocytes respectively to sites of infection (By similarity). Unlike most cytokines, which are secreted in soluble form, IL15 is expressed in association with its high affinity IL15RA on the surface of IL15-producing cells and delivers signals to target cells that express IL2RB and IL2RG receptor subunits. Binding to its receptor triggers the phosphorylation of JAK1 and JAK3 and the recruitment and subsequent phosphorylation of signal transducer and activator of transcription-3/STAT3 and STAT5. In mast cells, induces the rapid tyrosine phosphorylation of STAT6 and thereby controls mast cell survival and release of cytokines such as IL4 (PubMed:10882748, PubMed:19632221).|||Secreted http://togogenome.org/gene/10090:Scg3 ^@ http://purl.uniprot.org/uniprot/P47867 ^@ Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Expressed in various brain areas, with highest levels in the arcuate nucleus and the lateral hypothalamic area, as well as the paraventricular nucleus and the ventromedial hypothalamus (at protein level).|||Interacts with CHGA (PubMed:12388744). Interacts with secretogranin II/SCG2 (By similarity). Interacts (via C-terminus) with CPE (PubMed:16219686).|||Member of the granin protein family that regulates the biogenesis of secretory granules (PubMed:16219686). Acts as a sorting receptor for intragranular proteins including chromogranin A/CHGA (PubMed:12388744). May also play a role in angiogenesis (PubMed:28330905). Promotes endothelial proliferation, migration and tube formation through MEK/ERK signaling pathway (By similarity).|||Secreted|||secretory vesicle|||secretory vesicle membrane http://togogenome.org/gene/10090:Or10j27 ^@ http://purl.uniprot.org/uniprot/Q8VG32 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Rexo4 ^@ http://purl.uniprot.org/uniprot/Q6PAQ4 ^@ Function|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the REXO4 family.|||Can bind ESR1 and ESR2. This interaction is abrogated by estrogen and augmented by tamoxifen treatment (By similarity).|||Intron retention.|||May function as an exonuclease.|||nucleolus http://togogenome.org/gene/10090:Pdcl2 ^@ http://purl.uniprot.org/uniprot/Q78Y63 ^@ Caution|||Similarity ^@ Belongs to the phosducin family.|||Reported to be expressed in male and female germ cells, to be up-regulated at the protein level as early as 3 hours after chorionic gonadotropin treatment in the ovary, and to interact with 14-3-3 proteins (PubMed:12424248). However, the publication has been retracted due to image duplication and manipulation. The nucleotide sequence has been confirmed by other studies (PubMed:11116088). http://togogenome.org/gene/10090:Masp2 ^@ http://purl.uniprot.org/uniprot/Q91WP0 ^@ Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the peptidase S1 family.|||Dimerization and MBL2 binding requires calcium ions.|||Homodimer; disulfide-linked. Binds MBL2. Isoform 2 binds to MASP1. Binds SERPING1 (By similarity).|||Plasma.|||Secreted|||Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase (By similarity).|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Narf ^@ http://purl.uniprot.org/uniprot/Q9CYQ7 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the NARF family.|||Interacts with LMNA and binds to the farnesylated C-terminal domain.|||Nucleus http://togogenome.org/gene/10090:Mettl7b ^@ http://purl.uniprot.org/uniprot/Q9DD20 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the methyltransferase superfamily.|||Endoplasmic reticulum membrane|||Lipid droplet|||Thiol S-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-l-methionine to hydrogen sulfide and other thiol compounds including dithiothreitol, 7alpha-thiospironolactone, L-penicillamine, and captopril. http://togogenome.org/gene/10090:Rap1gap2 ^@ http://purl.uniprot.org/uniprot/Q5SVL6 ^@ Function|||Sequence Caution|||Subcellular Location Annotation ^@ Contaminating sequence. Sequence of unknown origin in the N-terminal part.|||Cytoplasm|||GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state. http://togogenome.org/gene/10090:Mettl6 ^@ http://purl.uniprot.org/uniprot/Q8BVH9 ^@ Disruption Phenotype|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the methyltransferase superfamily. METL family.|||Cytoplasm|||Due to intron retention.|||Mice were born with normal Mendelian ratio without developmental defects (PubMed:28655767, PubMed:32923617). However, male show a significant reduction in body weight over time due to reduced energy expenditure (PubMed:32923617). Cells show reduced N(3)-methylcytidine modification in tRNA fractions (PubMed:28655767).|||Monomer (By similarity). Interacts with SARS1/SerRS; interaction is mediated via tRNA(Ser) and is required for N(3)-methylcytidine methylation (By similarity).|||Nucleus|||S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Ser), including tRNA(Ser)(UGA) and tRNA(Ser)(GCU) (PubMed:28655767). Interaction with SARS1/SerRS is required for N(3)-methylcytidine methylation (By similarity). http://togogenome.org/gene/10090:Rtel1 ^@ http://purl.uniprot.org/uniprot/Q0VGM9 ^@ Developmental Stage|||Disruption Phenotype|||Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.|||Able to elongate M.spretus telomeres in crosses between M.musculus and M.spretus.|||Belongs to the helicase family. RAD3/XPD subfamily.|||Death between days 10 and 11.5 of gestation with defects in the nervous system, heart, vasculature and extraembryonic tissues. Effects are due to severe genome instability and stochastic telomere loss in embryonic stem cells which display many chromosome breaks and fusions upon differentiation in vitro.|||Interacts with TERF1. Interacts (via PIP-box) with PCNA; the interaction is direct and essential for suppressing telomere fragility. Interacts with MMS19; the interaction mediates the association of RTEL1 with the cytosolic iron-sulfur protein assembly (CIA) complex.|||Nucleus|||The PIP-box (PCNA interacting peptide) motif mediates the interaction with PCNA and localization to replication foci.|||Widely expressed in 8.5 dpc and 9.5 dpc embryos with a more restricted expression pattern at 13.5 dpc-15.5 dpc. In general, expression in embryos coincides with areas of actively proliferating cells.|||Widely expressed. Expressed in spleen, thymus, Peyer patches, kidney, and intestine. Not expressed in brain, heart, lung, skeletal muscles, skin and white fat. In the adult gonad, it is highly expressed in the testis, mainly in the spermatogonia and meiotic spermatocytes. http://togogenome.org/gene/10090:Agpat5 ^@ http://purl.uniprot.org/uniprot/Q9D1E8 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.|||Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:15367102). Acts on LPA containing saturated or unsaturated fatty acids C15:0-C20:4 at the sn-1 position using C18:1-CoA as the acyl donor (By similarity). Also acts on lysophosphatidylethanolamine using oleoyl-CoA, but not arachidonoyl-CoA, and lysophosphatidylinositol using arachidonoyl-CoA, but not oleoyl-CoA (By similarity). Activity toward lysophosphatidylglycerol not detectable (By similarity).|||Endoplasmic reticulum membrane|||It is uncertain whether Met-1 or Met-12 is the initiator.|||Mitochondrion|||Nucleus envelope|||The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.|||Widely expressed. http://togogenome.org/gene/10090:Gzme ^@ http://purl.uniprot.org/uniprot/P08884 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the peptidase S1 family. Granzyme subfamily.|||Cytolytic granule|||This enzyme is probably necessary for target cell lysis in cell-mediated immune responses. http://togogenome.org/gene/10090:Ppil4 ^@ http://purl.uniprot.org/uniprot/Q9CXG3 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the cyclophilin-type PPIase family. PPIL4 subfamily.|||Nucleus|||PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). http://togogenome.org/gene/10090:Rab8b ^@ http://purl.uniprot.org/uniprot/P61028 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Associated with actin, delta-catenin and alpha and beta tubulins (By similarity). Interacts with OTOF (PubMed:18772196). Interacts with PEX5R (By similarity). Interacts with RAB3IP (By similarity). Interacts with VIM (By similarity). Interacts with CDH1 (By similarity). Interacts with MICALL2 (PubMed:18094055). Interacts with GDI1, GDI2, CHML and CHM; phosphorylation at Thr-72 disrupts these interactions (By similarity). Interacts with MICAL1 (By similarity).|||Belongs to the small GTPase superfamily. Rab family.|||Cell membrane|||Endosome membrane|||Phosphorylation of Thr-72 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.|||The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab may be involved in polarized vesicular trafficking and neurotransmitter release. May participate in cell junction dynamics in Sertoli cells (By similarity). May participate in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (By similarity).|||phagosome membrane http://togogenome.org/gene/10090:Mmp19 ^@ http://purl.uniprot.org/uniprot/Q2KHP2|||http://purl.uniprot.org/uniprot/Q3UW97|||http://purl.uniprot.org/uniprot/Q9JHI0 ^@ Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Activated by autolytic cleavage after Lys-98.|||Belongs to the peptidase M10A family.|||Binds 1 zinc ion per subunit.|||Binds 2 Zn(2+) ions per subunit.|||Can bind about 5 Ca(2+) ions per subunit.|||Cell membrane|||Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis (By similarity). Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin (By similarity).|||Expressed in proliferating chondrocytes in the chondroepiphysis during musculoskeletal development.|||Highly expressed in the liver. Expressed in the arterial tunica media of large blood vessels.|||The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.|||Tyrosine phosphorylated by PKDCC/VLK.|||extracellular matrix http://togogenome.org/gene/10090:Nudc ^@ http://purl.uniprot.org/uniprot/O35685 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the nudC family.|||Detected in fetal and adult brain, in particular in the ventricular zone of the embryonic forebrain and in the embryonic cortical plate. Highly expressed in brain cortex from new born and adult mice. Detected in the choroid plexus and in ependymal cells in embryonic brain.|||Interacts with PLK1 (By similarity). Interacts with PAFAH1B1 (PubMed:9601647). Part of a complex containing PLK1, NUDC, dynein and dynactin (PubMed:11734602). Interacts with DCDC1 (By similarity). Interacts with EML4 (via WD repeats) (By similarity).|||Midbody|||Nucleus|||Plays a role in neurogenesis and neuronal migration (PubMed:11734602). Necessary for correct formation of mitotic spindles and chromosome separation during mitosis (By similarity). Necessary for cytokinesis and cell proliferation (By similarity).|||Reversibly phosphorylated on serine residues during the M phase of the cell cycle. Phosphorylation on Ser-275 and Ser-327 is necessary for correct formation of mitotic spindles and chromosome separation during mitosis. Phosphorylated by PLK and other kinases (By similarity).|||Up-regulated in silica-treated macrophages.|||cytoskeleton|||spindle http://togogenome.org/gene/10090:Papss1 ^@ http://purl.uniprot.org/uniprot/Q3TUA8|||http://purl.uniprot.org/uniprot/Q60967|||http://purl.uniprot.org/uniprot/Q6NZM8 ^@ Function|||Similarity|||Subunit|||Tissue Specificity ^@ Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway (PubMed:7493984). Required for normal biosynthesis of sulfated L-selectin ligands in endothelial cells (By similarity).|||Expressed in the neonatal brain and in cartilage.|||Homodimer.|||In the C-terminal section; belongs to the sulfate adenylyltransferase family.|||In the N-terminal section; belongs to the APS kinase family. http://togogenome.org/gene/10090:Rpain ^@ http://purl.uniprot.org/uniprot/J3QN46|||http://purl.uniprot.org/uniprot/Q0PL81|||http://purl.uniprot.org/uniprot/Q0PL82|||http://purl.uniprot.org/uniprot/Q9CWY9 ^@ Function|||PTM|||Subcellular Location Annotation|||Subunit ^@ Interacts with the RPA1 subunit of RPA complex.|||Mediates the import of RPA complex into the nucleus, possibly via some interaction with importin beta. Sumoylation mediates the localization of RPA complex into the PML body of the nucleus, thereby participating in RPA function in DNA metabolism (By similarity).|||Nucleus|||Sumoylated; required for localization in the nuclear PML body and transport of RPA complex in PML body. Upon UV irradiation and during S phase, it is desumoylated, releasing RPA complex that is translocated to sites of DNA damage. Sumoylation takes place at different Lys residues (By similarity). http://togogenome.org/gene/10090:Ehd1 ^@ http://purl.uniprot.org/uniprot/Q80ZZ0|||http://purl.uniprot.org/uniprot/Q9WVK4 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes vesiculation of endocytic membranes (By similarity). Acts in early endocytic membrane fusion and membrane trafficking of recycling endosomes (PubMed:15930129, PubMed:20159556). Recruited to endosomal membranes upon nerve growth factor stimulation, indirectly regulates neurite outgrowth (By similarity). Plays a role in myoblast fusion (PubMed:21177873). Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating a function in neuronal APP processing (PubMed:24373286). Plays a role in the formation of the ciliary vesicle (CV), an early step in cilium biogenesis. Proposed to be required for the fusion of distal appendage vesicles (DAVs) to form the CV by recruiting SNARE complex component SNAP29. Is required for recruitment of transition zone proteins CEP290, RPGRIP1L, TMEM67 and B9D2, and of IFT20 following DAV reorganization before Rab8-dependent ciliary membrane extension. Required for the loss of CCP110 form the mother centriole essential for the maturation of the basal body during ciliogenesis (By similarity).|||Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.|||Cell membrane|||Cytoplasmic vesicle|||Early endosome membrane|||Endosome membrane|||Expression is already noted at day 9.5 in the limb buds and pharyngeal arches and at day 10.5 in sclerotomes, at various elements of the branchial apparatus (mandible and hyoid), and in the occipital region. At day 15.5 expression peaks in cartilage, preceding hypertrophy and ossification, and at day 17.5 there is no expression in the bones.|||Highly expressed in testis. Also expressed in kidney, heart, intestine, and brain.|||Homooligomer, and heterooligomer with EHD2, EHD3 and EHD4, ATP-binding is required for heterooligomerization (By similarity). Interacts (via EH domain) with MICALL1 (via NPF1 motif); the interaction is direct and recruits EHD1 to membranes (PubMed:23572513). Interacts with RAB35; the interaction is indirect through MICALL1 and recruits EHD1 to membranes (PubMed:23572513). Interacts (via EH domain) with PACSIN2 (via NPF motifs); regulates localization to tubular recycling endosome membranes (PubMed:15930129). Interacts with PACSIN1 (PubMed:15930129). Interacts with RAB8A (By similarity). Interacts with FER1L5 (via second C2 domain) (PubMed:21177873). Interacts with MYOF (PubMed:21177873). Interacts with ZFYVE20 (By similarity). Interacts (via EH domain) with RAB11FIP2 (By similarity).|||Membrane|||Recycling endosome membrane|||The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.|||cilium membrane http://togogenome.org/gene/10090:Phka2 ^@ http://purl.uniprot.org/uniprot/A2AHQ7|||http://purl.uniprot.org/uniprot/Q8BWJ3 ^@ Activity Regulation|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.|||Belongs to the phosphorylase b kinase regulatory chain family.|||By phosphorylation of various serine residues and by calcium.|||Cell membrane|||Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin (By similarity).|||Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin.|||Membrane|||Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin. http://togogenome.org/gene/10090:Col26a1 ^@ http://purl.uniprot.org/uniprot/Q91VF6 ^@ Developmental Stage|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ At 9.5 dpc it is expressed in the somites and in mesenchymal cells of the head and the branchial arches. At 14.5 dpc it is expressed in the surrounding mesenchyme of the kidney and the inner ear. Expression is also observed in the spinal nerves and ganglia, the mesenchyme of the skull, the diaphragm, and the skeletal muscles.|||Homotrimer or heterotrimer.|||Hydroxylated on proline residues.|||May be due to a competing acceptor splice site.|||N-glycosylated.|||Specifically expressed in the testis and ovary in adult tissues.|||extracellular matrix http://togogenome.org/gene/10090:Abr ^@ http://purl.uniprot.org/uniprot/A0A2X0U2A7|||http://purl.uniprot.org/uniprot/E9PUE7|||http://purl.uniprot.org/uniprot/Q5SSL4 ^@ Disruption Phenotype|||Domain|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ In hippocampal subregions, expressed at similarly high levels in the dentate gyrus and CA1 regions, but lower in the CA3 region.|||Interacts with DLG4.|||Mutant mice show impaired spatial and object recognition memory with reduced maintenance of long-term potentiation (LTP) in Schaffer collateral-CA1 pyramidal neuron synapses.|||Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (By similarity). Functions as an important negative regulator of neuronal RAC1 activity (PubMed:20962234). Regulates macrophage functions such as CSF-1 directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687).|||Synapse|||The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.|||axon|||dendritic spine http://togogenome.org/gene/10090:Defb41 ^@ http://purl.uniprot.org/uniprot/Q30KP6 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the beta-defensin family.|||By androgens.|||Has bactericidal activity.|||Isoform 2 is epididymis-specific and expressed mainly in the proximal caput.|||Isoform 2 may play a role in the antimicrobial protection of sperm and urogenital tract epithelia.|||Secreted http://togogenome.org/gene/10090:Ptprf ^@ http://purl.uniprot.org/uniprot/A2A8L5 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.|||Expressed in the cell of the T lineage but not in cells of any other hemopoietic lineage.|||Interacts with GRIP1. Interacts with PPFIA1, PPFIA2 and PPFIA3. Interacts with PTPRF.|||Membrane|||Possible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity (By similarity).|||The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. http://togogenome.org/gene/10090:Fam50a ^@ http://purl.uniprot.org/uniprot/Q9WV03 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the FAM50 family.|||Interacts with EFTUD2, a component of the spliceosome U5 complex. Interacts with DDX41, a component of the spliceosome C complex.|||Nucleus|||Probably involved in the regulation of pre-mRNA splicing.|||Widely expressed in embryonic and adult tissues. http://togogenome.org/gene/10090:Mboat4 ^@ http://purl.uniprot.org/uniprot/P0C7A3 ^@ Activity Regulation|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the membrane-bound acyltransferase family.|||Catalyzes ghrelin acylation at 'Ser-3' using preferentially octanoyl-CoA, hexanoyl-CoA and decanoyl-CoA as acyl-CoA donors leading to ghrelin activity (PubMed:18267071, PubMed:24045953, PubMed:28134508, PubMed:18669668, PubMed:18443287, PubMed:19501572). In vitro uses also acyl-CoA donors of different lengths from short-chain (C2) to long-chain fatty acids (C16) knowing that acyl-CoA donors from butanoyl-CoA (C4) to dodecanoyl-CoA (C12) are more efficient compared to longer acyl-CoA donors, such as myristoyl-CoA (C14) and palmitoyl-CoA (C16) that are not efficient (PubMed:19501572).|||Endoplasmic reticulum membrane|||Highly expressed in stomach and pancreas (PubMed:18267071). Lower expression in small intestine and colon (PubMed:18267071). Very low expression in testis (PubMed:18267071).|||Inactive octanoyltransferase activity.|||Inhibited by 1-[2-cyano-3,12-dioxooleana-1,9(11)- dien-28-oyl]ethylamide (CDDO-EA) with an IC(50) of 60 uM (PubMed:28134508). Inhibited by Fe3+ and Cu2+ and the O-acyltransferase activity is completely blocked over 5 mM Fe3+ and 0.5 mM Cu2+ (PubMed:19501572).|||Mice display a complete lack of octanoylated ghrelin in blood.|||Monomer.|||Not glycosylated. http://togogenome.org/gene/10090:Cyba ^@ http://purl.uniprot.org/uniprot/B3VQI8|||http://purl.uniprot.org/uniprot/Q61462 ^@ Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the p22phox family.|||Cell membrane|||Composed of a heavy chain (beta) and a light chain (alpha). Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts with NCF1 (via SH3 domain).|||Composed of a heavy chain (beta) and a light chain (alpha). Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts with NCF1 (via SH3 domain). Interacts with DUOX1, DUOX2 and TPO. Interacts with NOX3 and NOX4. Interacts with calprotectin (S100A8/9) (By similarity). Interacts with SH3PXD2A (PubMed:19755709). Interacts with GBP7 (PubMed:21551061).|||Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide.|||Membrane|||Mice show defects in invadopodia biogenesis (PubMed:19755709). Mutants have a very sever defect in controlling bacterial replication (PubMed:28351984). Mice show spontaneous trunk curland head bobbing and fail to exhibit contact-rghting reflex (PubMed:28351984).|||Phosphorylation at Thr-147 enhances NADPH oxidase activity by promoting p47phox binding.|||The heme prosthetic group could be coordinated with residues of the light chain, the heavy chain, or both, and it is possible that more than one heme is present per cytochrome b-245.|||The strongest level of expression is found in kidney, peritoneal neutrophils and peritoneal macrophages, and a lower level in spleen and small intestine. Very low level of expression can be noted in brain, liver, testis, and heart.|||Ubiquitinated at Lys-149 likely by RNF145. http://togogenome.org/gene/10090:Akr1c21 ^@ http://purl.uniprot.org/uniprot/Q91WR5 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the aldo/keto reductase family.|||Cytoplasm|||Detected in kidney and brain.|||Inhibited by high concentrations of substrate.|||Monomer.|||NADP-dependent 17-alpha-hydroxysteroid dehydrogenase that converts 5-alpha-androstane-3,17-dione into androsterone. Has lower 3-alpha-hydroxysteroid dehydrogenase activity. Has broad substrate specificity and acts on various 17-alpha-hydroxysteroids, 17-ketosteroids, 3-alpha hydroxysteroids and 3-ketosteroids. Reduction of keto groups is strictly stereoselective. Reduction of 17-ketosteroids yields only 17-alpha-hydroxysteroids. Likewise, reduction of 3-ketosteroids yields only 3-alpha-hydroxysteroids. http://togogenome.org/gene/10090:Crlf2 ^@ http://purl.uniprot.org/uniprot/Q8CII9 ^@ Domain|||Function|||Induction|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type I cytokine receptor family. Type 5 subfamily.|||Cell membrane|||High level of expression in liver, lung and testis. Also expressed in heart, brain, spleen, thymus and bone marrow. Highly expressed in progenitors and myeloid cells. Isoform 2 is expressed in primary hemotopoietic cells.|||Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2. Implicated in the development of the hematopoietic system.|||Secreted|||The TSLP receptor is a heterodimer of CRLF2 and IL7R. Binding of TSLP to CRLF2/TSLPR is a mechanistic prerequisite for recruitment of IL7R to the high-affinity ternary complex.|||The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.|||The box 1 motif is required for JAK interaction and/or activation.|||Up-regulated in the myeloid 32D cell line by granulocyte colony-stimulating factor (G-CSF). http://togogenome.org/gene/10090:Itga3 ^@ http://purl.uniprot.org/uniprot/Q62470 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the integrin alpha chain family.|||Cell membrane|||Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-3 associates with beta-1. Interacts with HPS5. Interacts with FAP (seprase); the interaction occurs at the cell surface of invadopodia membrane in a collagen-dependent manner.|||Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration.|||Isoform 1 and isoform 2 are expressed in heart and brain. Only isoform 1 is detected in lung.|||filopodium membrane|||invadopodium membrane http://togogenome.org/gene/10090:Pced1a ^@ http://purl.uniprot.org/uniprot/Q6P1Z5 ^@ Similarity ^@ Belongs to the PC-esterase family. http://togogenome.org/gene/10090:Sos2 ^@ http://purl.uniprot.org/uniprot/Q02384 ^@ Function|||Tissue Specificity ^@ Expressed in most embryonic and adult tissues.|||Promotes the exchange of Ras-bound GDP by GTP. http://togogenome.org/gene/10090:Mkks ^@ http://purl.uniprot.org/uniprot/Q9JI70 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TCP-1 chaperonin family.|||Component of a complex composed at least of MKKS, BBS10, BBS12, TCP1, CCT2, CCT3, CCT4, CCT5 and CCT8. Interacts with STUB1. Interacts with BBS2 (via coiled coil domain). Interacts with CCDC28B. Interacts with BBS12. Interacts with SMARCC1, a component of the SWI/SNF complexes; the interaction takes place predominantly in the cytoplasm and may modulate SMARCC1 location (By similarity). Interacts with DLEC1 (By similarity).|||Mice demonstrate retinal degeneration, failure of spermatozoa flagella formation, elevated blood pressure, olfactory deficits, and social dominance, but no polydactyly nor vaginal abnormalities. The phenotype closely resembles the phenotype of other mouse models of Bardet-Biedl syndrome (Bbs2 deficient and Bbs4 deficient). Obesity is associated with hyperleptinemia and resistance to the anorectic and weight-reducing effects of leptin. Although mice are resistant to the metabolic actions of leptin, mice remain responsive to the effects of leptin on renal sympathetic nerve activity and arterial pressure and develop hypertension. BBS mice have decreased hypothalamic expression of proopiomelanocortin (POMC). BBS genes play an important role in maintaining leptin sensitivity in POMC neurons.|||Nucleus|||Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis (By similarity). Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:28753627). May play a role in protein processing in limb, cardiac and reproductive system development. May play a role in cytokinesis (By similarity).|||Widely expressed in adult and fetal tissues. Expressed in the developing heart, brain retina, limb buds, as well as in the developing neural tube. Expressed in the embryo in the first and second branchial arches. Expressed in parafin embedded tissue sections of brain, kidney, retina, olfactory epithelium and the ependymal layer of ventricles. Detected only in restricted regions of these tissue sections, including the ciliated border of renal tubules, the connecting cilium and the inner and outer nuclear layers of retina, and the ciliated layer of olfactory epithelia.|||centrosome|||cytosol http://togogenome.org/gene/10090:1700028K03Rik ^@ http://purl.uniprot.org/uniprot/Q3KQP7 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expressed in embryonic ovaries at embryonic day 16.5 (at protein level).|||Homooligomer (PubMed:30949703). Interacts with SHOC1 (PubMed:30746471). Interacts with SYCP1 and SYCE3 (PubMed:30949703).|||Mice show a massive germline loss and infertility in both males and females (PubMed:30746471, PubMed:30949703). Defects in meiotic prophase progression and meiotic recombination seen in spermatocytes and oocytes (PubMed:30746471). Meiocytes fail to achieve complete synapsis and show repair of double-strand breaks without formation of crossovers (PubMed:30746471).|||Plays a key role in reinforcing the integrity of the central element of the synaptonemal complex (SC) thereby stabilizing SC, ensuring progression of meiotic prophase I in male and female germ cells (PubMed:30949703). Promotes homologous recombination and crossing-over in meiotic prophase I via its association with SHOC1 (PubMed:30746471). Required for the localization of TEX11 and MSH4 to recombination intermediates (PubMed:30746471).|||Testis (at protein level). http://togogenome.org/gene/10090:Kif24 ^@ http://purl.uniprot.org/uniprot/Q6NWW5 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.|||Expressed in brain, spinal cord, and small intestine.|||Interacts with CCP110, CEP97, TALPID3 (By similarity). Interacts with MPHOSPH9 (By similarity).|||Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles. Mediates depolymerization of microtubules of centriolar origin, possibly to suppress aberrant cilia formation. Following activation by NEK2 involved in disassembly of primary cilium during G2/M phase but does not disassemble fully formed ciliary axonemes. As cilium assembly and disassembly is proposed to coexist in a dynamic equilibrium may suppress nascent cilium assembly and, potentially, ciliar re-assembly in cells that have already disassembled their cilia ensuring the completion of cilium removal in the later stages of the cell cycle (By similarity). Plays an important role in recruiting MPHOSPH9, a negative regulator of cilia formation to the distal end of mother centriole (By similarity).|||centriole|||centrosome http://togogenome.org/gene/10090:C1ra ^@ http://purl.uniprot.org/uniprot/Q8CG16 ^@ Function|||PTM|||Similarity|||Subunit ^@ Belongs to the peptidase S1 family.|||C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains, each of which is activated by cleavage into two chains, A and B, connected by disulfide bonds (By similarity).|||C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.|||The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. http://togogenome.org/gene/10090:Vmn1r243 ^@ http://purl.uniprot.org/uniprot/K9J7G6 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Arhgap39 ^@ http://purl.uniprot.org/uniprot/P59281 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Prpsap2 ^@ http://purl.uniprot.org/uniprot/Q05BD4|||http://purl.uniprot.org/uniprot/Q5SWZ0|||http://purl.uniprot.org/uniprot/Q8R574 ^@ Function|||Similarity|||Subunit ^@ Belongs to the ribose-phosphate pyrophosphokinase family.|||Binds to PRPS1 and PRPS2.|||Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis. http://togogenome.org/gene/10090:Col6a4 ^@ http://purl.uniprot.org/uniprot/A2AX52 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the type VI collagen family.|||Collagen VI acts as a cell-binding protein.|||In newborn, it is expressed in lung, kidney, brain, intestine, skin, sternum and, at weak level, calvaria. In adult, it is almost absent with some weak expression in ovary and very weak expression in spleen, lung, uterus and brain.|||Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.|||Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-4(VI) or alpha-5(VI) or alpha-6(VI).|||extracellular matrix http://togogenome.org/gene/10090:Ptgs2 ^@ http://purl.uniprot.org/uniprot/Q05769 ^@ Activity Regulation|||Cofactor|||Developmental Stage|||Disruption Phenotype|||Function|||Induction|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Acetylated at Ser-565 by SPHK1. During neuroinflammation, acetylation by SPHK1 promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.|||Belongs to the prostaglandin G/H synthase family.|||Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.|||By cytokines and mitogens.|||Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PTGS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PTGS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.|||Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate, with a particular role in the inflammatory response (PubMed:22942274, PubMed:12925531, PubMed:20463020, PubMed:20810665, PubMed:21489986). The cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:22942274, PubMed:12925531, PubMed:20463020, PubMed:20810665, PubMed:21489986). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (By similarity). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (By similarity). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (By similarity). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (By similarity). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (By similarity). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (By similarity). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (PubMed:29662056).|||During colonic wound repair, highly up-regulated (more than 1600-fold) in the mesenchyme of the wound bed 2 days after injury as compared to uninjured mucosa. Further increase in expression is observed at day 4 following injury (close to 2200-fold). Down-regulated at day 6 (only 93-fold increase as compared to uninjured mucosa).|||Endoplasmic reticulum membrane|||Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level).|||Homodimer.|||Inhibited by the nonsteroidal anti-inflammatory drugs aspirin, naproxen, diclofenac, meclofenamic acid, indomethacin and their analogs.|||Microsome membrane|||Mutant mice exhibit defects in colonic mucosal wound repair.|||Nucleus inner membrane|||Nucleus outer membrane|||PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.|||S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526.|||The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site. http://togogenome.org/gene/10090:Pon3 ^@ http://purl.uniprot.org/uniprot/Q62087 ^@ Cofactor|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the paraoxonase family.|||Binds 2 calcium ions per subunit.|||Glycosylated.|||Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents (By similarity).|||Homodimer.|||The signal sequence is not cleaved.|||extracellular space http://togogenome.org/gene/10090:Prpf31 ^@ http://purl.uniprot.org/uniprot/Q8CCF0 ^@ Domain|||Function|||Miscellaneous|||Sequence Caution|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the PRP31 family.|||Cajal body|||Contaminating sequence. The C-terminus matches chromosome 19 region.|||Identified in the spliceosome B complex. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Interacts with a complex formed by SNU13 and U4 snRNA, but not with SNU13 or U4 snRNA alone. The complex formed by SNU13 and PRPF31 binds also U4atac snRNA, a characteristic component of specific, less abundant spliceosomal complexes. Interacts with PRPF6/U5 snRNP-associated 102 kDa protein. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts (via its NLS) with CTNNBL1. Interacts with USH1G (By similarity).|||Interacts with the snRNP via the Nop domain.|||Involved in pre-mRNA splicing as component of the spliceosome. Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome.|||May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.|||Nucleus|||Nucleus speckle|||The coiled coil domain is formed by two non-contiguous helices. http://togogenome.org/gene/10090:Bsn ^@ http://purl.uniprot.org/uniprot/O88737 ^@ Disruption Phenotype|||Function|||Miscellaneous|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cytoplasm|||Expressed in brain and retina.|||Incompl.|||Interacts with PCLO, ERC2/CAST1, RIMS1 and UNC13A (PubMed:19812333). Interacts with TPRG1L (PubMed:17869247). Interacts with DYNLL1 and DYNLL2; these interactions potentially link PTVs to dynein and myosin V motor complexes (By similarity). Interacts with ATG5; this interaction is important for the regulation of presynaptic autophagy (PubMed:28231469). Interacts (via C-terminus) with TRIO (via N-terminus) (By similarity). Interacts with CTBP1 (By similarity). Interacts with SIAH1; this interaction negatively regulates SIAH1 E3 ligase activity (By similarity).|||Mice show a reduced excitability attributed to inactivation of a fraction of brain glutamatergic synapses. At these synapses, vesicles are clustered and docked in normal numbers, but were unable to fuse. In retina, mutants lacking functional BSN showed normal retinal anatomy, but synapses lacked anchoring of the photoreceptor ribbon to the presynaptic active zone resulting in impaired photoreceptor synaptic transmission (PubMed:12628168). Knockdown of both Bassoon/BSN and Piccolo/PCLO leads to the formation of presynaptic autophagosomes.|||Myristoylated. The N-terminal myristoylation is not sufficient for presynaptic localization (By similarity).|||Presynaptic active zone|||Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released (PubMed:12628168, PubMed:12628169, PubMed:19812333). After synthesis, participates in the formation of Golgi-derived membranous organelles termed Piccolo-Bassoon transport vesicles (PTVs) that are transported along axons to sites of nascent synaptic contacts (By similarity). At the presynaptic active zone, regulates the spatial organization of synaptic vesicle cluster, the protein complexes that execute membrane fusion and compensatory endocytosis (By similarity). Functions also in processes other than assembly such as the regulation of specific presynaptic protein ubiquitination by interacting with SIAH1 or the regulation of presynaptic autophagy by associating with ATG5 (By similarity) (PubMed:28231469). Mediates also synapse to nucleus communication leading to reconfiguration of gene expression by associating with the transcriptional corepressor CTBP1 and by subsequently reducing the size of its pool available for nuclear import (By similarity).|||cytoskeleton|||synaptic vesicle membrane http://togogenome.org/gene/10090:Sumf2 ^@ http://purl.uniprot.org/uniprot/Q8BPG6 ^@ Caution|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Although strongly similar to formylglycine-generating enzyme, lacks the catalytic Cys residues that bind the catalytic copper. The catalytic copper is required to activate oxygen and catalyze oxidative C-H activation.|||Belongs to the sulfatase-modifying factor family.|||Endoplasmic reticulum lumen|||Homodimer and heterodimer with SUMF1.|||Lacks formylglycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1.|||The non-canonical ER retention motif mediates retention of the protein in the endoplasmic reticulum. http://togogenome.org/gene/10090:H2-DMb2 ^@ http://purl.uniprot.org/uniprot/Q31099 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the MHC class II family.|||Membrane http://togogenome.org/gene/10090:Borcs5 ^@ http://purl.uniprot.org/uniprot/E9Q2W8|||http://purl.uniprot.org/uniprot/Q9D920 ^@ Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor. Thereby, it may indirectly play a role in cell spreading and motility.|||Belongs to the BORCS5 family.|||Component of the BLOC-one-related complex (BORC) which is composed of BLOC1S1, BLOC1S2, BORCS5, BORCS6, BORCS7, BORCS8, KXD1 and SNAPIN. Interacts with ARL8B, KIF5A, KLC1 and PLEKHM2; links the lysosomal BORC complex to the microtubule plus-end-directed kinesin motor.|||Lysosome membrane|||Membrane|||Myristoylation at Gly-2 mediates attachment to lysosome membranes. http://togogenome.org/gene/10090:Plxna4 ^@ http://purl.uniprot.org/uniprot/Q80UG2 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the plexin family.|||Cell membrane|||Coreceptor for SEMA3A. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.|||Expressed in the developing nervous system. Widely expressed in both the central and peripheral nervous systems. Expressed in the peripheral ganglia, somatosensory, olfactory, visual, auditory and equilibrium systems.|||Interacts with NRP1 and NRP2.|||No visible phenotype. Mice exhibit defasciculation of the facial branchiomotor nerve and of the ophthalmic branch of the trigeminus, with variable severity. In mice lacking both Plxna3 and Plxna4, migrating neurons do not show the normal response to Sema3A and Sema3F and do not migrate away from these semaphorins (in vitro). http://togogenome.org/gene/10090:Abca4 ^@ http://purl.uniprot.org/uniprot/O35600 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylethanolamine. Phospholipids translocase activity is highly reduced by berylium fluoride and aluminum floride. N-ethylmaleimide inhibits phospholipid translocase activity.|||Belongs to the ABC transporter superfamily. ABCA family.|||Delayed dark adaptation but normal final rod threshold.|||Endoplasmic reticulum|||Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like the 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine from the lumen to the cytoplasmic leaflet of photoreceptor outer segment disk membranes, where N-cis-retinylidene-phosphatidylethanolamine (N-cis-R-PE) is then isomerized to its all-trans isomer (N-trans-R-PE) and reduced by RDH8 to produce all-trans-retinol (all-trans-rol) and therefore prevents the accumulation of excess of 11-cis-retinal and its schiff-base conjugate and the formation of toxic bisretinoid (PubMed:10852960, PubMed:10412977, PubMed:22735453). Displays both ATPase and GTPase activity that is strongly influenced by the lipid environment and the presence of retinoid compounds (By similarity). Binds the unprotonated form of N-retinylidene-phosphatidylethanolamine with high affinity in the absence of ATP and ATP binding and hydrolysis induce a protein conformational change that causes the dissociation of N-retinylidene-phosphatidylethanolamine (By similarity).|||Membrane|||N-glycosylated.|||Phosphorylation is independent of light exposure and modulates ATPase activity.|||Proteolytic cleavage by trypsin leads to a 120-kDa N-terminal fragment and a 115-kDa C-terminal fragment that are linked through disulfide bonds.|||Retinal-specific (PubMed:9202155). Seems to be exclusively found in the rims of rod photoreceptor cells.|||The second extracellular domain (ECD2, aa 1395-1680) undergoes conformational change in response to its specific interaction with its substrate all-trans-retinal. Nucleotide binding domain 1 (NBD1, aa 854-1375) binds preferentially and with high affinity with the 11-cis retinal.|||photoreceptor outer segment http://togogenome.org/gene/10090:Gm20874 ^@ http://purl.uniprot.org/uniprot/J3QNI1 ^@ Similarity ^@ Belongs to the XLR/SYCP3 family. http://togogenome.org/gene/10090:Gm13277 ^@ http://purl.uniprot.org/uniprot/Q8CD73 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha/beta interferon family.|||Secreted http://togogenome.org/gene/10090:Bank1 ^@ http://purl.uniprot.org/uniprot/Q80VH0 ^@ Function|||PTM|||Subunit|||Tissue Specificity ^@ Interacts with LYN, ITPR1 and ITPR2.|||Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores. Promotes Lyn-mediated phosphorylation of IP3 receptors 1 and 2 (By similarity).|||Phosphorylated on tyrosines upon BCR activation.|||Specifically expressed in spleen. Highly expressed in immature B-cells and recirculating B-cells, and at low levels in pro-B and pre-B cells. http://togogenome.org/gene/10090:Uqcr11 ^@ http://purl.uniprot.org/uniprot/Q9CPX8 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the UQCR11/QCR10 family.|||Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:19026783).|||Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. QCR10 has a role in CIII assembly and RIP1 stability.|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Pramel25 ^@ http://purl.uniprot.org/uniprot/A2A8N2|||http://purl.uniprot.org/uniprot/Q3UX09|||http://purl.uniprot.org/uniprot/Q5XG66 ^@ Similarity ^@ Belongs to the PRAME family. http://togogenome.org/gene/10090:Gxylt1 ^@ http://purl.uniprot.org/uniprot/Q3UHH8 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the glycosyltransferase 8 family.|||Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.|||Membrane http://togogenome.org/gene/10090:Rd3 ^@ http://purl.uniprot.org/uniprot/Q8BRE0 ^@ Disease Annotation|||Function|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ A spontaneous mutation leading to a frameshift and in an unstable truncated protein lacking the C-terminal 89 amino acids causes retinal degeneration. Homozygotes mice (called rd-3) display retinal degeneration, beginning at 3 weeks of age, characterized by complete loss of photoreceptor rod cells by 5 weeks, and cones by 8 weeks.|||Cytoplasm|||Endosome|||Expressed in the retina and in particular in the inner nuclear layer, in rod and cone outer segments, in the outer nuclear layer, in the outer plexiform layer and in the ganglion cell layer.|||Monomer (By similarity). Interacts with GUCY2E; promotes the exit of GUCY2E from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments (PubMed:21078983). The interaction with GUCY2E negatively regulates its activity (By similarity). Interacts with GUCY2F; promotes the exit of GUCY2F from the endoplasmic reticulum and its trafficking to the photoreceptor outer segments (PubMed:21078983). The interaction with GUCY2F negatively regulates its activity (By similarity). Interacts with GUK1; up-regulates GUK1 activity (By similarity).|||Nucleus|||Photoreceptor inner segment|||Plays a critical role in the regulation of enzymes involved in nucleotide cycle in photoreceptors (PubMed:21078983, PubMed:27471269). Inhibits the basal catalytic activity and the GCAP-stimulated activity of GUCY2E and GUCY2F, two retinal guanylyl cyclases involved in the production of cGMP in photoreceptors (PubMed:27471269). Involved in the transport of GUCY2E and GUCY2F to their target sites in the photoreceptor outer segment (PubMed:21078983). Up-regulates the activity of GUK1, a kinase that also plays an essential role for recycling GMP and indirectly, cGMP (By similarity). Plays an important role for the survival of rods and cones in the retina (PubMed:8486383, PubMed:17186464).|||perinuclear region|||photoreceptor outer segment http://togogenome.org/gene/10090:Spata5 ^@ http://purl.uniprot.org/uniprot/Q3UMC0 ^@ Domain|||Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ ATP-dependent chaperone, which plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Acts together with AFG2B, AIRIM and CINP (By similarity). May be involved in morphological and functional mitochondrial transformations during spermatogenesis (PubMed:10734318).|||Aberrantly expressed at the malignant conversion stage in a clonal epidermal model of chemical carcinogenesis.|||Associates with pre-60S ribosomal particles. Interacts with AIRIM.|||Belongs to the AAA ATPase family. AFG2 subfamily.|||Cytoplasm|||Expressed in testis; with localization to spermatogonia and early spermatocytes in the basal compartment of the seminiferous tubules (at early stages of spermatogenesis). Very weak signals observed in spleen and skin.|||Mitochondrion|||The first ATP-binding region binds ATP with low affinity whereas the second ATP-binding region binds ATP with high affinity.|||spindle http://togogenome.org/gene/10090:Vmn2r124 ^@ http://purl.uniprot.org/uniprot/K7N789 ^@ Subcellular Location Annotation ^@ Cell membrane|||Membrane http://togogenome.org/gene/10090:Tnfrsf14 ^@ http://purl.uniprot.org/uniprot/A0A1W2P7D5|||http://purl.uniprot.org/uniprot/Q80WM9 ^@ Caution|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the tumor necrosis factor receptor superfamily.|||Cell membrane|||Expressed at mucosal sites including colon and pulmonary epithelial cells (PubMed:22801499). Expressed in naive T cells (PubMed:19915044).|||Interacts with TRAF2, TRAF3 and TRAF5 (By similarity). Interacts (via CRD1/TNFR-Cys 1) with CD160; this interaction is direct (PubMed:18193050). Interacts (via CRD1/TNFR-Cys 1) with BTLA; this interaction is direct (PubMed:15568026).|||Lacks conserved residue(s) required for the propagation of feature annotation.|||N-glycosylated.|||Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a complex stimulatory and inhibitory signaling network (By similarity). Signals via the TRAF2-TRAF3 E3 ligase pathway to promote immune cell survival and differentiation (PubMed:19915044). Participates in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. In response to ligation of TNFSF14/LIGHT, delivers costimulatory signals to T cells, promoting cell proliferation and effector functions (By similarity). Interacts with CD160 on NK cells, enhancing IFNG production and anti-tumor immune response (PubMed:25711213). In the context of bacterial infection, acts as a signaling receptor on epithelial cells for CD160 from intraepithelial lymphocytes, triggering the production of antimicrobial proteins and pro-inflammatory cytokines (PubMed:22801499). Upon binding to CD160 on activated CD4+ T cells, down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (By similarity). May interact in cis (on the same cell) or in trans (on other cells) with BTLA (PubMed:19915044, PubMed:15568026). In cis interactions, appears to play an immune regulatory role inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, can predominate during adaptive immune response to provide survival signals to effector T cells (PubMed:19915044, PubMed:15568026).|||The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for interaction with CD160 and BTLA. http://togogenome.org/gene/10090:Lman2l ^@ http://purl.uniprot.org/uniprot/P59481 ^@ Function|||Subcellular Location Annotation ^@ Endoplasmic reticulum membrane|||Golgi apparatus membrane|||May be involved in the regulation of export from the endoplasmic reticulum of a subset of glycoproteins. May function as a regulator of ERGIC-53 (By similarity). http://togogenome.org/gene/10090:Rufy3 ^@ http://purl.uniprot.org/uniprot/Q9D394 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Cell projection|||Cytoplasm|||Endomembrane system|||Expressed during the embryonic brain development from 11.5 dpc, onwards (PubMed:24720729). Expressed in the upper layers of the cortex at 11.5 dpc (PubMed:24720729). Expressed in the intermediate zone to the cortical plate of the cortex at 18.5 dpc (PubMed:24720729). Expressed in neurons (at protein level) (PubMed:24720729).|||Expressed in brain (at protein level) (PubMed:24720729).|||Interacts (via N-terminus) with FSCN1; this interaction induces neuron axon development (PubMed:24720729). Interacts with DBN1 (PubMed:24720729). Interacts with PAK1 (By similarity). Interacts (via C-terminus) with Ras-related Rab-5 proteins (By similarity). Interacts (via C-terminus) with Ras-related Rap-2 proteins (By similarity). Interacts with PIK3CA and PIK3R1 (By similarity).|||Perikaryon|||Phosphorylated by PAK1. Isoform 1 is partially phosphorylated.|||Plays a role in the generation of neuronal polarity formation and axon growth (PubMed:24720729). Implicated in the formation of a single axon by developing neurons (PubMed:24720729). May inhibit the formation of additional axons by inhibition of PI3K in minor neuronal processes (By similarity). Plays a role in the formation of F-actin-enriched protrusive structures at the cell periphery (By similarity). Plays a role in cytoskeletal organization by regulating the subcellular localization of FSCN1 and DBN1 at axonal growth cones (PubMed:24720729). Promotes gastric cancer cell migration and invasion in a PAK1-dependent manner (By similarity).|||filopodium|||growth cone|||invadopodium|||lamellipodium http://togogenome.org/gene/10090:Gria4 ^@ http://purl.uniprot.org/uniprot/Q9Z2W8 ^@ Domain|||Function|||Miscellaneous|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA4 subfamily.|||Cell membrane|||Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Interacts with EPB41L1 via its C-terminus (By similarity). Found in a complex with GRIA1, GRIA2, GRIA3, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5 and PRKCG (By similarity).|||Palmitoylated. Depalmitoylated upon glutamate stimulation. Cys-611 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-837 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).|||Phosphorylated at Ser-862 by PRKCG; phosphorylation increases plasma membrane-associated GRI4 expression.|||Postsynaptic cell membrane|||Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate (By similarity).|||The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.|||The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > glutamate > kainate.|||dendrite http://togogenome.org/gene/10090:Zranb1 ^@ http://purl.uniprot.org/uniprot/Q7M760 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the peptidase C64 family.|||Cytoplasm|||Interacts with TRAF6. Interacts with APC.|||Nucleus|||The OTU domain mediates the deubiquitinating activity.|||The RanBP2-type zinc fingers, also called NZFs, mediate the interaction with ubiquitin and determine linkage specificity. RanBP2-type zinc fingers 1 and 2 (also named NZF1 and NZF2) specifically recognize and bind 'Lys-29'- and 'Lys-33'-linked ubiquitin. RanBP2-type zinc finger 3 (also named NZF3) binds 'Lys-33'-linked ubiquitin and shows weak binding to 'Lys-6'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin chains but it does not interact with 'Lys-29'-linked chains.|||The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts with ubiquitin hydrophobic patch and contributes to linkage specificity.|||Ubiquitin thioesterase, which specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin (By similarity). Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones (By similarity). Positive regulator of the Wnt signaling pathway that deubiquitinates APC protein, a negative regulator of Wnt-mediated transcription (By similarity). Acts as a regulator of autophagy by mediating deubiquitination of PIK3C3/VPS34, thereby promoting autophagosome maturation (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Required in the stress fiber dynamics and cell migration (By similarity). http://togogenome.org/gene/10090:Inhba ^@ http://purl.uniprot.org/uniprot/Q04998|||http://purl.uniprot.org/uniprot/Q3UY39 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TGF-beta family.|||Dimeric, linked by one or more disulfide bonds. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B. Activin A is a homodimer of beta-A. Activin B is a homodimer of beta-B. Activin AB is a dimer of beta-A and beta-B. Interacts with FST and FSTL3 (By similarity).|||Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.|||Secreted|||Uterus, ovary and liver. http://togogenome.org/gene/10090:Cdpf1 ^@ http://purl.uniprot.org/uniprot/Q8R3A2 ^@ Similarity ^@ Belongs to the CDPF1 family. http://togogenome.org/gene/10090:Ahsa1 ^@ http://purl.uniprot.org/uniprot/Q8BK64 ^@ Function|||Induction|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acts as a co-chaperone of HSP90AA1 (PubMed:29127155). Activates the ATPase activity of HSP90AA1 leading to increase in its chaperone activity (PubMed:29127155). Competes with the inhibitory co-chaperone FNIP1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (By similarity). Competes with the inhibitory co-chaperone TSC1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155).|||Belongs to the AHA1 family.|||By heat shock and treatment with the HSP90 inhibitor 17-demethoxygeldanamycin (17AAG).|||Endoplasmic reticulum|||Interacts with HSPCA/HSP90 (By similarity). Interacts with HSP90AA1; the interaction activates HSP90AA1 ATPase activity (PubMed:29127155). Interacts with HSP90AB1 (PubMed:22022502). Interacts with GCH1 (By similarity). Interacts with SRPK1 (By similarity). Interacts with FLCN (By similarity).|||Phosphorylation at Tyr-223 enhances binding to chaperone HSP90AA1.|||cytosol http://togogenome.org/gene/10090:Sntb1 ^@ http://purl.uniprot.org/uniprot/Q99L88 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex.|||Belongs to the syntrophin family.|||Cell junction|||Monomer and homodimer (Probable). Interacts with the viral HTLV-1 TAX protein and other members of the syntrophin family: SNTA1 and SNTB2 (By similarity). Interacts with the dystrophin protein DMD and related proteins DTNA and UTRN and with the sodium channel proteins SCN4A and SCN5A. Interacts with DTNB (PubMed:10893187).|||Phosphorylated by CaM-kinase II.|||The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity).|||The PH 1 domain mediates the oligomerization in a calcium dependent manner.|||The SU domain binds calmodulin in a calcium-dependent manner.|||Ubiquitous. Expressed at high levels in the liver.|||cytoskeleton|||sarcolemma http://togogenome.org/gene/10090:Ccdc110 ^@ http://purl.uniprot.org/uniprot/Q3V125 ^@ Subcellular Location Annotation ^@ Nucleus http://togogenome.org/gene/10090:Pate3 ^@ http://purl.uniprot.org/uniprot/B3GLJ3 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the PATE family.|||Secreted http://togogenome.org/gene/10090:Lca5l ^@ http://purl.uniprot.org/uniprot/A0A5H1ZRL0|||http://purl.uniprot.org/uniprot/Q8C0X0 ^@ Similarity ^@ Belongs to the LCA5 family. http://togogenome.org/gene/10090:Psmd12 ^@ http://purl.uniprot.org/uniprot/Q9D8W5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the proteasome subunit p55 family.|||Component of the 19S proteasome regulatory particle complex (PubMed:16857966). The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (By similarity). The regulatory particle is made of a lid composed of 9 subunits including PSMD12, a base containing 6 ATPases and few additional components (By similarity). Interacts with ERCC6 (By similarity).|||Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. http://togogenome.org/gene/10090:Ndufs2 ^@ http://purl.uniprot.org/uniprot/Q91WD5 ^@ Cofactor|||Disruption Phenotype|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the complex I 49 kDa subunit family.|||Binds 1 [4Fe-4S] cluster.|||Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Component of the iron-sulfur (IP) fragment of the enzyme. Interacts with NDUFAF3. Interacts with NDUFAF7 (By similarity). Interacts with CERS2 (PubMed:32279995).|||Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:26437605, PubMed:29887397, PubMed:31297047). Essential for the catalytic activity and assembly of complex I (PubMed:26437605, PubMed:29887397, PubMed:31297047). Redox-sensitive, critical component of the oxygen-sensing pathway in the pulmonary vasculature which plays a key role in acute pulmonary oxygen-sensing and hypoxic pulmonary vasoconstriction (PubMed:30922174). Plays an important role in carotid body sensing of hypoxia (PubMed:26437605, PubMed:29887397). Essential for glia-like neural stem and progenitor cell proliferation, differentiation and subsequent oligodendrocyte or neuronal maturation (PubMed:31297047).|||Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to stabilize the early intermediate complex.|||Knockout mice show early perinatal death and major defects in the CNS, compromising especially the postnatal development of dorsal cortex, corpus callosum, hippocampus and cerebellum (PubMed:31297047). Neonatal neurogenesis and gliogenesis are deeply impaired (PubMed:31297047).|||Mitochondrion inner membrane http://togogenome.org/gene/10090:Kpna3 ^@ http://purl.uniprot.org/uniprot/O35344|||http://purl.uniprot.org/uniprot/Q543M7 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the importin alpha family.|||Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.|||Cytoplasm|||Detected more or less in all tissues examined (Ehrlich ascites tumor cells, testis, kidney, spleen, liver, heart, lung, thymus, skeletal muscle, cerebellum and brain (without cerebellum)).|||Forms a complex with importin subunit beta-1. Interacts with DDX21. Interacts with NCBP1, NCBP2/CBP20 and NCBP3. Interacts with RCC1.|||Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.|||Functions in nuclear protein import.|||Nucleus|||The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity).|||The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity). http://togogenome.org/gene/10090:Utp4 ^@ http://purl.uniprot.org/uniprot/Q8R2N2 ^@ Developmental Stage|||Function|||PTM|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Chromosome|||Expressed in liver.|||In 11.5 day embryos, highly and predominantly expressed in liver, with lower expression in somites, brain and craniofacial structures. Expression significantly decreases in 12.5 day embryos and in the newborn.|||Interacts with HIVEP1 Interacts with NOL11. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. May be a component of the proposed t-UTP subcomplex of the ribosomal small subunit (SSU) processome containing at least UTP4, WDR43, HEATR1, UTP15, WDR75.|||May be phosphorylated during mitosis; may control the association of this protein with WRD43 and UTP15.|||Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted d Involved in SSU pre-rRNA processing at sites A', A0, 1 and 2b. Required for optimal pre-ribosomal RNA transcription by RNA polymerase. May be a transcriptional regulator.|||nucleolus http://togogenome.org/gene/10090:Me1 ^@ http://purl.uniprot.org/uniprot/P06801|||http://purl.uniprot.org/uniprot/Q3TQP6 ^@ Cofactor|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the malic enzymes family.|||Catalyzes the oxidative decarboxylation of (S)-malate in the presence of NADP(+) and divalent metal ions, and decarboxylation of oxaloacetate.|||Cytoplasm|||Divalent metal cations. Prefers magnesium or manganese.|||Homotetramer. http://togogenome.org/gene/10090:Nr1i2 ^@ http://purl.uniprot.org/uniprot/O54915|||http://purl.uniprot.org/uniprot/Q0P525 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the nuclear hormone receptor family.|||Belongs to the nuclear hormone receptor family. NR1 subfamily.|||Heterodimer with RXRA (By similarity). Interacts with NCOA1 (By similarity). Interacts (via domain NR LBD) with CRY1 and CRY2 in a ligand-dependent manner (PubMed:28751364).|||Nuclear receptor that binds and is activated by a variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, endogenous compounds and drugs. Response to specific ligands is species-specific, due to differences in the ligand-binding domain. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes (By similarity). Activated by naturally occurring steroids such as pregnenolone and progesterone, the cholesterol metabolite 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol, synthetic glucocorticoids and antiglucocorticoids and 16-alpha-carbonitrile (PCN).|||Nucleus http://togogenome.org/gene/10090:Icmt ^@ http://purl.uniprot.org/uniprot/Q3U4N2|||http://purl.uniprot.org/uniprot/Q9EQK7 ^@ Caution|||Developmental Stage|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.|||Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.|||During cerebellar development expression was low before postnatal day P6 and dramatically increased after P12.|||Endoplasmic reticulum membrane|||Highly enriched in adult cerebellum, with a low level expression in other brain regions.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane http://togogenome.org/gene/10090:Zfp142 ^@ http://purl.uniprot.org/uniprot/G5E869 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||May be involved in transcriptional regulation.|||Nucleus http://togogenome.org/gene/10090:Fosl2 ^@ http://purl.uniprot.org/uniprot/P47930 ^@ Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bZIP family. Fos subfamily.|||Controls osteoclast survival and size (PubMed:18548006). As a dimer with JUN, activates LIF transcription (PubMed:18548006). Activates CEBPB transcription in PGE2-activated osteoblasts (By similarity).|||Heterodimer; with JUN (PubMed:18548006). Interacts with the BAF multiprotein chromatin-remodeling complex subunits SMARCB1 and SMARCD1 (PubMed:29272704). Interacts with ARID1A and JUN (PubMed:29272704).|||Mutant pups die within a week after birth. They exhibit severe osteopenia as early as 18.5 dpc, with a 50% decrease in mineralized bone. Osteoblast numbers are not altered. The number, the relative surface covered by osteoclasts and the mean osteoclast surface are increased 3-fold, 5-fold and 2-fold, respectively. Bone resorption activity is increased. This phenotype is due to hypoxia in long bones resulting from placental defects.|||Nucleus http://togogenome.org/gene/10090:Adamts13 ^@ http://purl.uniprot.org/uniprot/A2ALB3|||http://purl.uniprot.org/uniprot/A7LM19|||http://purl.uniprot.org/uniprot/Q769J6 ^@ Activity Regulation|||Caution|||Cofactor|||Developmental Stage|||Domain|||Function|||PTM|||Polymorphism|||Subcellular Location Annotation|||Tissue Specificity ^@ Binds 1 zinc ion per subunit.|||Binds 4 Ca(2+) ions.|||Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.|||Increases steadly with the age of embryo, reaching highest levels in embryonic tissues of 19 days of gestation.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||O-glycosylated (By similarity). O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS13. May also be C-glycosylated on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and also N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).|||Plasma. Expression is consistently high in liver, medium in lung and spleen, low in skeletal muscle and undetectable in heart, brain, kidney and testis.|||Secreted|||The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction (By similarity).|||The precursor is processed by a furin endopeptidase which cleaves off the pro-domain.|||The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency.|||Two variants (Adamts13L and Adamts13S) were isolated that differed in the insertion of an intracisternal A particle (IAP) retrotransposon including a premature stop at the position 1036. In Adamts13S the C-terminal two TSP type-1 and two CUB domains are replaced with a 16-amino acid sequence derived from the IAP, this variant exhibited vWF cleaving activities in vitro. The IAP insertion is strain-specific and is found in BALB/c, C3H/He, C57BL/6 and DBA/2 strains, but not in the 129/Sv strain.|||Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Dependence on calcium for proteolytic activity is mediated by the high affinity site (By similarity). http://togogenome.org/gene/10090:Tmem267 ^@ http://purl.uniprot.org/uniprot/H3BJ86|||http://purl.uniprot.org/uniprot/Q8VDR5 ^@ Subcellular Location Annotation ^@ Membrane http://togogenome.org/gene/10090:Fsip1 ^@ http://purl.uniprot.org/uniprot/Q9D3V5 ^@ Developmental Stage|||Similarity|||Subunit|||Tissue Specificity ^@ Belongs to the FSIP1 family.|||Detected in male germ cells and testis.|||First detected in testis of 18 day old mice.|||May interact with AKAP4. http://togogenome.org/gene/10090:Eif1ad3 ^@ http://purl.uniprot.org/uniprot/Q3TQZ4 ^@ Function|||Similarity ^@ Belongs to the eIF-1A family.|||Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1. http://togogenome.org/gene/10090:Zfp219 ^@ http://purl.uniprot.org/uniprot/Q6IQX8 ^@ Developmental Stage|||Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the krueppel C2H2-type zinc-finger protein family.|||C2H2-type zinc-finger domains 5 and 6 are important for the interaction with SOX9.|||Expressed in proliferating chondrocytes in the tibia at embryonic stage 15.5 dpc (at protein level). Expressed in limb buds at stage 11.5 dpc, where it colocalizes with Col2a1 and Sox9.|||Highly expressed in primary chondrocytes, heart, pancreas and testis.|||Interacts with SOX9 (via C-terminus).|||Nucleus|||Transcriptional regulator (PubMed:20940257). Recognizes and binds 2 copies of the core DNA sequence motif 5'-GGGGG-3' (PubMed:20940257). Binds to the HMGN1 promoter and may repress HMGN1 expression (By similarity). Regulates SNCA expression in primary cortical neurons (By similarity). Binds to the COL2A1 promoter and activates COL2A1 expression, as part of a complex with SOX9 (PubMed:20940257). Plays a role in chondrocyte differentiation (PubMed:20940257). http://togogenome.org/gene/10090:Or5m11b ^@ http://purl.uniprot.org/uniprot/A2ATE0 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Adig ^@ http://purl.uniprot.org/uniprot/Q8R400 ^@ Function|||Induction|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the adipogenin family.|||Induced during adipose conversion of 3T3-L1 cells. Up-regulated in 3T3-L1 adipocytes by troglitazone which stimulates PPARG expression during differentiation. Down-regulated in 3T3-L1 adipocytes exposed to TNF-alpha and to retinoic acid.|||Membrane|||Nucleus|||Plays a role in stimulating adipocyte differentiation and development.|||Selectively expressed in adipose tissue where it is particularly enriched in brown adipose tissue. In adipose tissue, expressed exclusively in adipocytes and not in the stromal-vascular cell population. Expressed at much lower levels in heart, stomach and muscle and barely detected in kidney and lung. http://togogenome.org/gene/10090:Gstp1 ^@ http://purl.uniprot.org/uniprot/P19157 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the GST superfamily. Pi family.|||Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). Participates in the formation of novel hepoxilin regioisomers. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.|||Cytoplasm|||Homodimer. Interacts with CDK5 (By similarity).|||Mitochondrion|||Nucleus|||Ubiquitously expressed. http://togogenome.org/gene/10090:Vmn1r159 ^@ http://purl.uniprot.org/uniprot/K7N701 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Tmtc3 ^@ http://purl.uniprot.org/uniprot/A0A0R4J173|||http://purl.uniprot.org/uniprot/G5E8C4|||http://purl.uniprot.org/uniprot/Q8BRH0 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the TMTC family.|||Endoplasmic reticulum|||Membrane|||Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3. Involved in the positive regulation of proteasomal protein degradation in the endoplasmic reticulum (ER), and the control of ER stress response. http://togogenome.org/gene/10090:Fbxl6 ^@ http://purl.uniprot.org/uniprot/Q9QXW0 ^@ Function|||Subunit ^@ Directly interacts with SKP1 and CUL1.|||Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. http://togogenome.org/gene/10090:Ndst4 ^@ http://purl.uniprot.org/uniprot/Q9EQW8 ^@ Function|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfotransferase 1 family. NDST subfamily.|||Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Has low deacetylase activity but high sulfotransferase activity.|||Expressed at low level in brain and throughout embryogenesis. Not expressed in other tissues.|||Golgi apparatus membrane|||Monomer.|||The presence of 4 different heparan sulfate N-deacetylase/N-sulfotransferase enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/sulfation reactions, whereas other later on fill in or extend already modified heparan sulfate sequences. http://togogenome.org/gene/10090:Prag1 ^@ http://purl.uniprot.org/uniprot/Q571I4 ^@ Caution|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the protein kinase superfamily.|||Catalytically inactive protein kinase that acts as a scaffold protein (By similarity). Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (By similarity). Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (By similarity). Acts as a critical coactivator of Notch signaling (PubMed:25038227).|||Cytoplasm|||Deficient mice shown complete embryonic lethality (PubMed:25038227).|||Despite of the presence of a putative ATP-binding motif, this protein does not bind ATP, suggesting that it has no protein kinase activity.|||Homodimer (By similarity). Dimerization leads to the catalytic activation of CSK (By similarity). Interacts (via C-terminus) with RND2 (By similarity). Interacts with CSK (via SH2 domain) in a Tyr-391 phosphorylation-dependent manner; this interaction potentiates kinase activity of CSK (By similarity). Interacts with NOTCH1 intracellular domain (N1ICD) (PubMed:25038227). Forms a complex with PRAG1, N1ICD and MAML1, in a MAML1-dependent manner (PubMed:25038227).|||Nucleus|||Phosphorylated by CSK on Tyr-238, Tyr-343, and Tyr-391; Tyr-391 is a primary site of phosphorylation.|||The dimerization region encompasses helices both from the N- and C-terminal of the protein kinase domain.|||focal adhesion http://togogenome.org/gene/10090:Gk ^@ http://purl.uniprot.org/uniprot/B1ASZ3|||http://purl.uniprot.org/uniprot/Q3TEN9|||http://purl.uniprot.org/uniprot/Q3TET2|||http://purl.uniprot.org/uniprot/Q64516 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the FGGY kinase family.|||Cytoplasm|||Key enzyme in the regulation of glycerol uptake and metabolism.|||Mitochondrion outer membrane http://togogenome.org/gene/10090:Or52i2 ^@ http://purl.uniprot.org/uniprot/E9Q549 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Prkcd ^@ http://purl.uniprot.org/uniprot/P28867|||http://purl.uniprot.org/uniprot/Q3TGE4|||http://purl.uniprot.org/uniprot/Q53YN4 ^@ Activity Regulation|||Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Autophosphorylated and/or phosphorylated at Thr-505, within the activation loop; phosphorylation at Thr-505 is not a prerequisite for enzymatic activity (By similarity). Autophosphorylated at Ser-299 (By similarity). Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3 (By similarity). Phosphorylated at Tyr-311, Tyr-332 and Tyr-565; phosphorylation of Tyr-311 and Tyr-565 following thrombin or zymosan stimulation potentiates its kinase activity (By similarity). Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2 (By similarity). Phosphorylated at Tyr-311 through a SYK and SRC mechanism downstream of C-type lectin receptors activation, promoting its activation (PubMed:22265677).|||Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (PubMed:11976686, PubMed:11976687). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (PubMed:19917613). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA (By similarity). In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:18025218). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:22265677). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (PubMed:9705322). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (By similarity). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (By similarity). Phosphorylates SMPD1 which induces SMPD1 secretion (By similarity).|||Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression.|||Cell membrane|||Cytoplasm|||Endomembrane system|||Interacts with PDPK1 (via N-terminal region) (By similarity). Interacts with RAD9A (By similarity). Interacts with CDCP1 (By similarity). Interacts with MUC1 (By similarity). Interacts with VASP (By similarity). Interacts with CAVIN3 (PubMed:9054438). Interacts with PRKD2 (via N-terminus and zing-finger domain 1 and 2) in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation (By similarity). Interacts with PLSC3; interaction is enhanced by UV irradiation (By similarity).|||Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP.|||Isoform 1 is highly expressed in developing pro- and pre-B-cells and moderately in mature T-cells. Isoform 2 is highly expressed in testis and ovary and at a lower level in thymocytes, brain and kidney.|||Mice are viable up to 1 year despite detection of auto-immune disease in these animals. They exhibit glomerulonephritis, splenomegaly and lymphadenopathy associated with B-cell expansion and defective B-cell tolerance to self-antigen.|||Mitochondrion|||Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine.|||Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine (By similarity).|||Nucleus|||Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation.|||The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor.|||The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner (By similarity).|||perinuclear region http://togogenome.org/gene/10090:Or5c1 ^@ http://purl.uniprot.org/uniprot/Q8VF22 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Psme3 ^@ http://purl.uniprot.org/uniprot/P61290|||http://purl.uniprot.org/uniprot/Q4FK54 ^@ Disruption Phenotype|||Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1 (By similarity).|||Belongs to the PA28 family.|||Cytoplasm|||Growth retardation, small body size, and reduces significantly the percentage of cells that enter the S phase.|||Homoheptamer; the stability of the heptamer is essential for the specific activation of the trypsine-like subunit and inhibition of the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits of the proteasome (By similarity). Interacts with p53/TP53 and MDM2 (By similarity). Interacts with MAP3K3 (PubMed:12650640). Associates with the proteasome (By similarity). Interacts with CCAR2 (By similarity). Interacts with PSME3IP1 (via C-terminus); the interaction is direct and promotes the association of PSME3 with the 20S proteasome (By similarity). Interacts with COIL; the interaction is inhibited by PSME3IP1 (By similarity).|||Nucleus|||Phosphorylated by MAP3K3. Phosphorylation at Ser-247 promotes its association with CCAR2 (By similarity).|||Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (By similarity).|||The C-terminal sequences affect heptamer stability and proteasome affinity. http://togogenome.org/gene/10090:Defa21 ^@ http://purl.uniprot.org/uniprot/Q8C1P2 ^@ Function|||Similarity|||Subcellular Location Annotation ^@ Belongs to the alpha-defensin family.|||May have microbicidal activities.|||Secreted http://togogenome.org/gene/10090:Hacl1 ^@ http://purl.uniprot.org/uniprot/Q9QXE0 ^@ Cofactor|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the TPP enzyme family.|||Binds 1 Mg(2+) ion per subunit.|||Binds 1 thiamine pyrophosphate per subunit.|||Homotetramer.|||Mice are viable and fertile and show no abnormal phenotype (PubMed:28629946, PubMed:29027957). However, upon dietary administration of phytol, phytanic acid accumulated in tissues, mainly in liver and serum of deficient mice. As a consequence of phytanic acid (or a metabolite) toxicity, deficent mice display a significant weight loss, absence of abdominal white adipose tissue, enlarged and mottled liver and reduced hepatic glycogen and triglyceride (PubMed:28629946). The presence of an other lyase, probably HCL2, can partially compensate for the lost of HCL1 (PubMed:28629946).|||Peroxisomal 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner (By similarity). Involved in the degradation of 3-methyl-branched fatty acids like phytanic acid and the shortening of 2-hydroxy long-chain fatty acids (By similarity). Plays a significant role in the biosynthesis of heptadecanal in the liver (PubMed:29027957).|||Peroxisome|||Predominanly expressed in liver. http://togogenome.org/gene/10090:Ifnk ^@ http://purl.uniprot.org/uniprot/Q4FZL7|||http://purl.uniprot.org/uniprot/Q7TSL0 ^@ Function|||Induction|||Miscellaneous|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the alpha/beta interferon family.|||Expressed at low levels in peritoneal macrophages.|||May play a role in the regulation of immune cell function.|||Secreted|||Transgenic mice overexpressing IFNK in the pancreas, develop insulin-dependent (type I) diabete.|||Upon exposure to double-stranded RNA and interferon-gamma. http://togogenome.org/gene/10090:Cenpt ^@ http://purl.uniprot.org/uniprot/Q3TJM4 ^@ Domain|||Function|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the CENP-T/CNN1 family.|||Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex is probably recruited on centromeres by the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Identified in a centromeric complex containing histones H2A, H2B, H3 and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1. Interacts (via N-terminus) with the NDC80 complex. Heterodimer with CENPW; this dimer coassembles with CENPS-CENPX heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex.|||Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis.|||Dynamically phosphorylated during the cell cycle. Phosphorylated during G2 phase, metaphase and anaphase, but not during telophase or G1 phase.|||Nucleus|||The largest part of the sequence forms an elongated and flexible stalk structure that is connected to a C-terminal globular domain with a histone-type fold.|||centromere|||kinetochore http://togogenome.org/gene/10090:Fshb ^@ http://purl.uniprot.org/uniprot/A0A0F7RQR1|||http://purl.uniprot.org/uniprot/Q60687 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the glycoprotein hormones subunit beta family.|||Expressed in the developing pituitary gland at 18.5 dpc.|||Heterodimer. The active follitropin is a heterodimer composed of an alpha chain/CGA shared with other hormones and a unique beta chain/FSHB shown here.|||Mice lacking Fshb are viable (PubMed:9020850). Females are infertile displaying abnormal uterus and ovaries that lacked corpora lutea. The infertility is due to impaired follicle maturation which appears before antral follicle formation (PubMed:9020850). Males are fertile and spermatogenesis proceeds normally. However, these mice display a reduced testes size and epididymal sperm count (PubMed:9020850, PubMed:11416011). The number of Sertoli cells is significantly reduced and their ability to support germ cell development is also affected (PubMed:11416011).|||Secreted|||Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled receptor, on target cells to activate downstream signaling pathways (By similarity). Follitropin is involved in follicle development and spermatogenesis in reproductive organs (PubMed:9020850, PubMed:11416011). http://togogenome.org/gene/10090:Spop ^@ http://purl.uniprot.org/uniprot/Q6ZWS8|||http://purl.uniprot.org/uniprot/Q9DBZ2 ^@ Domain|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the Tdpoz family.|||Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL (By similarity). In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability (By similarity).|||Homodimer and homooligomer. Heterodimer with SPOPL. Each dimer interacts with two CUL3 molecules. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX (By similarity). Interacts with MACROH2A1, PDX1/IPF1, GLI2 and GLI3.|||Nucleus|||Nucleus speckle|||The BTB (POZ) domain mediates dimerization and interaction with CUL3.|||The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as MACROH2A1 and BMI1.|||Widely expressed, mainly in pancreas and in particular in adult pancreatic insulin-producing beta cells and in a subset of exocrine acinar and duct cells. http://togogenome.org/gene/10090:Dusp28 ^@ http://purl.uniprot.org/uniprot/Q8BTR5 ^@ Function|||Similarity|||Subunit ^@ Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.|||Has phosphatase activity with the synthetic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (in vitro). Has almost no detectable activity with phosphotyrosine, even less activity with phosphothreonine and displays complete lack of activity with phosphoserine. The poor activity with phosphotyrosine may be due to steric hindrance by bulky amino acid sidechains that obstruct access to the active site.|||Monomer. http://togogenome.org/gene/10090:Clgn ^@ http://purl.uniprot.org/uniprot/P52194 ^@ Developmental Stage|||Disruption Phenotype|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the calreticulin family.|||Detected in testis (at protein level). Detected in testis.|||Endoplasmic reticulum membrane|||Functions during spermatogenesis as a chaperone for a range of client proteins that are important for sperm adhesion onto the egg zona pellucida and for subsequent penetration of the zona pellucida. Required for normal sperm migration from the uterus into the oviduct. Required for normal male fertility. Binds calcium ions.|||Interacts with PDILT and PPIB (By similarity). Interacts with ADAM2. Interacts with ADAM1A, ADAM1B and ADAM3; these are protein-coding genes in mouse but may be pseudogenes in other organisms.|||Male mice show normal mating behavior and produce morphologically normal sperm, but are nearly sterile. Mutant sperm fail to adhere to the egg zona pellucida and are generally unable to penetrate the egg extracellular matrix. In addition, mutant sperm display defects in migration from the uterus into the oviduct.|||Specifically expressed during male meiotic germ cell development. First detected in early pachytene spermatocytes. Expression is highest in elongating and round spermatids and decreases thereafter. Not detectable in mature spermatids. http://togogenome.org/gene/10090:Rxfp2 ^@ http://purl.uniprot.org/uniprot/A0A0J9YV81|||http://purl.uniprot.org/uniprot/B7ZMU5|||http://purl.uniprot.org/uniprot/E9Q0U9|||http://purl.uniprot.org/uniprot/Q91ZZ5 ^@ Caution|||Disease Annotation|||Function|||Similarity|||Subcellular Location Annotation|||Tissue Specificity ^@ Belongs to the G-protein coupled receptor 1 family.|||By homology with the human sequence, it is uncertain whether Met-1 is the initiator.|||Cell membrane|||Defects in Rxfp2 seems to be a cause of impaired testicular descent (known as cryptorchidism).|||Expressed in embryonic and adult gonads of males and females, as well in male gubernarculum. Expressed also in brain. Not detected in kidney, spleen and heart.|||Lacks conserved residue(s) required for the propagation of feature annotation.|||Membrane|||Receptor for relaxin. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. May also be a receptor for Leydig insulin-like peptide (INSL3) (By similarity). http://togogenome.org/gene/10090:Galns ^@ http://purl.uniprot.org/uniprot/Q571E4|||http://purl.uniprot.org/uniprot/Q8CC47 ^@ Cofactor|||PTM|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the sulfatase family.|||Binds 1 Ca(2+) ion per subunit.|||Homodimer.|||Lysosome|||The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.|||Widely expressed. Higher expression in liver and kidney. http://togogenome.org/gene/10090:Atp1a4 ^@ http://purl.uniprot.org/uniprot/Q9WV27 ^@ Activity Regulation|||Function|||Similarity|||Subcellular Location Annotation|||Subunit|||Tissue Specificity ^@ Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.|||Cell membrane|||Expressed at high levels in the testis and at low levels in the epididymis.|||Specifically inhibited by an endogenous cardiac glycoside, ouabain.|||The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit.|||This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility (By similarity). http://togogenome.org/gene/10090:Vps11 ^@ http://purl.uniprot.org/uniprot/Q91W86 ^@ Function|||Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the VPS11 family.|||Core component of at least two putative endosomal tethering complexes, the homotypic fusion and vacuole protein sorting (HOPS) complex and the class C core vacuole/endosome tethering (CORVET) complex. Their common core is composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, which in HOPS further associates with VPS39 and VPS41 and in CORVET with VPS8 and TGFBRAP1 (PubMed:25266290). Interacts with RAB5C (PubMed:25266290). Interacts with TGFBRAP1, MON1B, STX7, STX17, ECPAS, EZR, RDX, MSN (By similarity). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (PubMed:21411634). Interacts with PLEKHM1 (By similarity).|||Cytoplasmic vesicle|||Early endosome|||Late endosome membrane|||Lysosome membrane|||Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations. Required for fusion of endosomes and autophagosomes with lysosomes. Involved in cargo transport from early to late endosomes and required for the transition from early to late endosomes (By similarity).|||autophagosome|||clathrin-coated vesicle http://togogenome.org/gene/10090:Tas2r115 ^@ http://purl.uniprot.org/uniprot/Q7M719 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor T2R family.|||Membrane http://togogenome.org/gene/10090:Or1j14 ^@ http://purl.uniprot.org/uniprot/Q8VGK7 ^@ Similarity|||Subcellular Location Annotation ^@ Belongs to the G-protein coupled receptor 1 family.|||Cell membrane|||Membrane http://togogenome.org/gene/10090:Mrps28 ^@ http://purl.uniprot.org/uniprot/Q9CY16 ^@ Similarity|||Subcellular Location Annotation|||Subunit ^@ Belongs to the bacterial ribosomal protein bS1 family.|||Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.|||Mitochondrion